Epilepsia Epicongress

10th European Congress on Epileptology London, UK,

30 September–4 October 2012

Genetics 1Monday, 01 October 2012

001IDENTIFICATION OF NOVEL SYNTAXIN BINDINGPROTEIN 1 (STXBP1) MUTATIONS IN PATIENTS WITHSEVERE EARLY ONSET EPILEPTIC ENCEPHALOPA-THIES (EOEE)T. Dj�mi�*, P. Holmgren�, S. Weckhuysen�, A. Suls�, A. Jansen§,D. Hasaerts§, C. Dielman§, L. L. Klitten–, S. Von Spiczak**,I. Helbig**, R. S. Møller��, I. E. Scheffer��, H. Hjalgrim§§, andP. De Jonghe�

*University of Antwerp, Antwerp, Belgium; �VIB, Antwerp,Belgium; �Epilepsy Centre Kempenhaeghe, Oosterhout, TheNetherlands; §UZ Brussel, Brussel, Belgium; –University ofCopenhagen, Copenhagen, Denmark; **University MedicalCenter Schleswig-Holstein, Kiel, Germany; ��Danish EpilepsyCentre, Dianalund, Denmark; ��University of Melbourne,Melbourne, Australia; and §§Institute of Regional HealthServices Research, University of Southern Denmark, Odense,Denmark

Purpose: Identification of additional STXBP1 mutations in a largecohort of patients with EOEE and further delineating the phenotype ofSTXBP1 encephalopathy.

Method: We collected a cohort of 171 isolated patients with Ohtaharasyndrome, West syndrome and a wide range of unclassified EOEE. Pointmutations and deletions in STXBP1 have been described so we used twocomplementary strategies to detect both classes of variation. First, identi-fication of point mutations was done using Sangersequencing. Subse-quently we performed multiplex amplicon quantification (MAQ)analysis for detection of deletions.

Result: Four novel STXBP1 point mutations were identified in fourpatients. Three are missense mutations: p.G544V, p.I77N and p.R551C.The fourth, p.Q203X, is a nonsense mutation. DNA of parents of threepatients was available and these mutations were proven to occur de novo.p.G544V was found in a patient with a neonatal epileptic encephalopathythat evolved to West syndrome; p.I77N and Q203X in patients with neo-natal epileptic encephalopathy. The patient with the p.I77N mutationlater developed epileptic spasms without hypsarrythmia while the patientwith the p.R551C mutation had West syndrome from onset. Althoughone patient became seizure free after 2.5 months, all patients had severeintellectual disability. The MAQ analysis did not reveal any deletions inSTXBP1.

Conclusion: Our results confirm that patients with an STXBP1 encepha-lopathy present with severe epilepsy of very early onset and frequentlydevelop spasms early in disease course. Although mutation yield in thisstudy was lower than initially reported, STXBP1 screening should beconsidered in patients with severe EOEE of unknown etiology.

002SCREENING FOR SYNGAP1 MUTATIONS INPATIENTS WITH NON-SYNDROMIC ID AND EPILEPSYWITH MYOCLONIC ABSENCES OR MYOCLONICASTATIC EPILEPSYR. S. Møller*, F. F. Hamdan�, L. L. Klitten�, S. Dobrzeniecka�,D. Rochefort§, H. Hjalgrim–, G. A. Rouleau**, J. L. Michaud�,and N. Tommerup�

*Danish Epilepsy Centre, Dianalund, Denmark; �Center ofExcellence in Neuroscience of Universit� de Montr�al, Centre deRecherche du CHU Sainte-Justine, Montr�al, QC, Canada;�Wilhelm Johannsen Centre for Functional genome Research,University of Copenhagen, Copenhagen, Denmark; §Center ofExcellence in Neuroscience of Universit� de Montr�al, Centre deRecherche du Centre Hospitalier de l’Universit� de Montr�al,Department of Medicine, Universit� de Montr�al, Montr�al, QC,Canada; –Institute of Regional Health Services Research,University of Southern Denmark, Odense, Denmark; and**Center of Excellence in Neuroscience of Universit� deMontr�al, Centre de Recherche du Centre Hospitalier del’Universit� de Montr�al, Universit� de Montr�al, Montr�al, QC,Canada

Purpose: Epilepsy with Myoclonic Absences (EMA) and MyoclonicAstatic Epilepsy (MAE) are rare and severe childhood-onset epilepsies.The underlying etiologies of these syndromes are largely unsolved, butincreasing scientific evidence points to genetic factors for these severeepilepsies. Recently, it was shown that de novo mutations in the brain-expressed synapse gene SYNGAP1 cause Non-Syndromic IntellectualDisability (NSID). Worldwide, a total of 10 patients with mutations inthis gene have been described. Surprisingly, 7/10 published patients haveearly-onset of epilepsy with generalized seizures, mainly manifesting asabsence-, myoclonic- and/or atonic seizures.

Method: In search for an underlying cause of EMA and MAE, wesequenced the SYNGAP1 gene in a cohort of 25 patients with a combina-tion of NSID and early-onset of generalized seizures. Patients had EMA,MAE or unclassified epilepsy. DNA was extracted from blood and salivaspecimens according to standard protocols.

Result: In a single female patient we detected a mutation in the SYN-GAP1 gene (c.283dupC) which was absent in 669 healthy controls. Thismutation was predicted to cause a shift in reading frame and thereby cre-ate a truncated protein (p.His95ProX5). Surprisingly, this mutation wasinherited from a mildly affected father without epilepsy. A mosaic stateof the mutation in the father was detected via cloning and subsequentsequencing of blood- and saliva DNA.

Conclusion: We report the second patient with EMA and SYNGAP1mutation adding more evidence to SYNGAP1-dysfunction as cause ofEMA. In this study, we detected the first patient with an inherited SYN-GAP1 mutation and mosaicism in a mildly affected parent.

Epilepsia, 53(Suppl. 5):1–245, 2012doi: 10.1111/j.1528-1167.2012.03677.x

ABSTRACT

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003MUTATIONS IN CDKL5 AS A CAUSE OF EARLYONSET EPILEPSYM. Gos, D. Hoffman-Zacharska, M. Bartnik, K. Derwinska,I. Terczynska, H. Mazurkiewicz, T. Mazurczak, P. Stankiewicz,E. Szczepanik, E. Bocian, and J. BalInstitute of Mother and Child, Warsaw, Poland

Purpose: The cyclin-dependent kinase like 5 (CDKL5) gene, encodesserine-threonine kinase involved in the regulation MECP2 and DNAmethyltransferase I activities. The aim of the study was the molecularanalysis of CDKL5 gene, in which mutations are responsible for severeearly onset epileptic encephalopathy with infantile spasms, intellectualimpairment and Rett-like phenotype.

Method: Together, 29 patients with clinical symptoms suggestingCDKL5 mutation were referred to our laboratory for molecular testing.The multiplex ligation dependent probe amplification (MLPA) methodand SALSA MLPA P189 CDKL5 Kit containing probes specific for allCDKL5 exons were applied for the detection of gene deletions. In case ofdeletion presence, the results were validated with microarray-CGH,quantitative Real-Time PCR, long-range PCR or direct sequencingmethod.

Result: The MLPA analysis revealed the presence of deletions in threechildren with early onset epilepsy. In two, the deletion encompassed oneexon with flanking intron sequences (g.18542246_18553009del10764 –deletion of exon 18 and g.18492177-?_18492235+?del – deletion of exon4), in the second case the deletion was present in mosaic state. In the thirdcase, the sequencing analysis revealed the presence of small deletion inexon 6 - c.301_317del17bp (g.18507907_18507923del17) that partiallyoverlapped with the MLPA probe binding site leading to the decrease inMLPA signal. The mutation causes a frame shift starting at codon 101and creation of premature STOP codon three positions downstream. Fur-ther analysis of CDKL5 coding sequence in patients without deletion isin progress.

Conclusion: The MLPA analysis allowed to identify molecular cause ofearly onset epilepsy in 3/29 (10.3%) patients.

004PRRT2 MUTATIONS ARE THE MAJOR CAUSE OFBENIGN FAMILIAL INFANTILE SEIZURES (BFIS)Y. Weber*, J. Schubert*, R. Paravidino�, F. Becker*, A. Berger�,N. Bebek§, A. Bianchi–, K. Brockmann**, G. Capovilla��,B. Dalla Bernardina��, Y. Fukuyama§§, G. Hoffmann––,K. Jurkat-Rott***, A. Antonnen��, G. Kurlemann��, A. E.Lehesjoki§§§, F. Lehmann-Horn***, M. Mastrangelo–––,U. Mause****, S. M�ller*, B. Neubauer��, B. P�st��,D. Rating––, A. Robbiano�, S. Ruf§§§§, C. Schroeder§§§§,A. Seidel––––, N. Specchio*****, U. Stephani��, P. Striano��,J. Teichler§§§§§, D. Turkdogan§, F. Vigevano��, M. Viri–––,P. Bauer––––, F. Zara–––––, and H. Lerche**University of T�bingen, T�bingen, Germany; �Department ofNeuroscience, Genova, Italy; �Children's Hospital Harlaching,Munich, Germany; §Istanbul, Turkey; –Verona, Italy;**Gçttingen, Germany; ��Mantova, Italy; ��Arezzo, Italy;§§Tokyo, Japan; ––Heidelberg, Germany; ***Ulm, Germany; ��

Helsinki, Finland; ��M�nster, Germany; §§§Finland; –––Milano,Italy; ****Frankfurt, Germany; ��Giessen, Germany;��Hamburg, Germany; §§§§T�bingen, Germany; ––––Celle,Germany; *****Rome, Italy; ��Kiel, Germany; ��GasliniInstitute, University of Genova, Genova, Italy; §§§§§Z�rich,Switzerland; and –––––Institute Giannina Gaslini - Lab.Neurogenetics, Genova, Italy

Purpose: The PRRT2 gene, located on chromosome 16p11.2, is codingfor a presynaptic protein interacting with SNAP-25, which is importantfor the synaptic vesicle forming and transport in the brain. Mutations inPRRT2 have been described in paroxysmal kinesigenic dyskinesia(PKD) and ICCA (PKD with infantile seizures), and recently also in somefamilies with the syndrome of benign familial infantile seizures (BFIS)alone. All syndromes are linked to chromosome 16p12-q12. BFIS is char-acterized by (complex-)partial and generalized tonic-clonic seizuresoccurring often in clusters between 3 and 12 months of age typicallyresolving after weeks to months and normal psychomotor developmentin the patients.

Method: PRRT2 was sequenced in 49 BFIS families and three sporadiccases of Italian, German, Turkish and Japanese origin.

Result: We identified the previously described mutation c.649-650insCin an instable series of nine cytosines to occur in 77% of index cases. Fur-thermore, three novel mutations were found in three other families.

Conclusion: Our study reveals PRRT2 as the major gene for BFIS alone.In the presentation, we will describe our cohort and an overview of themutations found in the different disease entities.

Basic Science 1Monday, 01 October 2012

005SEIZURE-INDUCED BRAIN-BORN INFLAMMATIONAND BLOOD-BRAIN BARRIER DAMAGE ARE COUN-TERACTED BY ANAKINRA IN THE ISOLATED GUI-NEA PIG BRAIN PREPARATIONL. Librizzi*, T. Ravizza�, F. No��, A. Vezzani�, and M. DeCurtis**Neurological Institute C Besta Foundation, Milano, Italy; and�Mario Negri Institute for Pharmacological Research, Milano,Italy

Purpose: Recent findings support the concept that brain inflammationis an etiopathogenetic mechanism of epilepsy, promoting seizure pre-cipitation and recurrence. In this study we investigated if seizuresinduce brain inflammation independently on extracerebral factors andif brain-born inflammation is required and sufficient to maintain sei-zure activity and support blood-brain barrier (BBB) impairment. Forthis purpose, we studied the relationship between seizures, inflamma-tion and BBB permeability in a brain preparation isolated from extra-cerebral compartments.

Method: Epileptiform activity was induced by arterial perfusion ofbicuculline (50lM), a GABAa receptor antagonist. Seizure-inducedbrain inflammation was evaluated by quantitative immunohistochemi-cal analysis of IL-1b in parenchymal cells. BBB damage was assessedby extravasation of intravascular FITC-albumin. The effects of arteri-ally-perfused anakinra, a human recombinant IL-1b receptor antago-nist, were investigated on epileptiform discharges, brain inflammationand BBB damage.

Result: Seizures induction in the absence of extra-cerebral factors pro-moted the release of IL-1b from brain resident cells and enhanced itsbiosynthesis in astrocytes. Anakinra rapidly terminated seizures, pre-vented their recurrence and resolved seizure-associated BBB breack-down.

Conclusion: We demonstrated that (i) seizure activity determines arapid release of IL-1b from intrinsic brain cells, (ii) persistent braininflammation originates in glia, independently on peripheral factors, (iii)

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the clinically used the immunomodulator anakinra, abates both seizureduration and their recurrence, and the associated BBB breakdown, sup-porting the conclusion that brain-borne inflammation, independent onsystemic influences, initiates and sustains ictogenesis. This study sup-ports the use of specific anti-inflammatory drugs in clinical conditionsthat present with recurrent seizures, such as status epilepticus or drug-resistant chronic epilepsies.

006SEVERE FUNCTIONAL DEFECTS OF THE KV7.2CHANNEL CAUSED BY MUTATIONS ASSOCIATEDWITH EPILEPTIC ENCEPHALOPATHIESS. Maljevic*, M. Bock*, G. Orhan*, D. Shepers*,S. Weckhuysen�, S. Mandelstam�, A. Suls§, I. E. Scheffer–, P. DeJonghe**, and H. Lerche**Hertie Institute for Clinical Brain Research, Tuebingen,Germany; �University of Antwerp, Antwerp, Belgium; �7FloreyNeurosciences Institutes, Austin Health, Melbourne, Australia;§University of Antwerp, Wilrijk, Belgium; –Royal Children'sHospital, Parkville, VIC, Australia; and **NeurogeneticsGroup, Antwerp, Belgium

Purpose: Mutations in KCNQ2 and KCNQ3, encoding the voltage-gated potassium channels Kv7.2 and Kv7.3, cause Benign Familial Neo-natal Seizures (BFNS), an autosomal- dominant epilepsy syndrome withfavorable prognosis. However, some KCNQ2 mutations lead to moresevere clinical phenotypes, as reported for seven novel KCNQ2 muta-tions associated with an epileptic encephalopathy (Weckhuysen et al.,2012). In these patients, seizures were extremely refractory, profoundintellectual disability was present and the MRI revealed transient T1 andT2 hyperintensities of the basal ganglia and thalamus. To elucidate themechanisms behind the observed epileptic phenotypes we set out to func-tionally investigate these mutations.

Method: Using site-directed mutagenesis the mutations were insertedinto the KCNQ2 cDNA and potassium currents recorded in cRNA-injected Xenopus laevis oocytes, using a fully-automated injection and atwo-voltage clamp system.

Result: Mutations affecting the pore loop (p.A265P, p.T274M) and S6segment (p.G290D) yielded barely measurable potassium currents andexhibited a prominent dominant-negative effect on the WT currents ofKv7.2, Kv7.3 or Kv7.2/Kv7.3 channels. A depolarizing shift by about 10mV (p.I205V) or 60 mV (p.R213Q) was observed for the S4 segmentmutants, as well as for the C-terminal mutation p.R532W (~20 mV). Thesecond C-terminal mutation (p.M518V) reduced the maximal currentamplitude to one third of the WT.

Conclusion: Whereas haploinsufficiency of Kv7.2 presents the majorpathomechanism of BFNS with only a few mutations exhibiting a domi-nant-negative effect, our electrophysiological findings indicate dramaticfunctional deficits for the majority of the epileptic encephalopathy muta-tions, which could present a plausible explanation for the more seriousclinical phenotype.

007COMPLEMENT C3 UPREGULATION CONTRIBUTESTO A SUSTAINED INFLAMMATORY RESPONSE ANDPERPETUATION OF SEIZURE FOCI IN A PILOCAR-PINE MODEL OF TEMPORAL LOBE EPILEPSYI. Kharatishvili, D. She, Z. Shan, N. Kurniawan, and D. ReutensCentre for Advanced Imaging, Brisbane, Qld, Australia

Purpose: Inflammation plays a prominent role in the affected brain tis-sue in temporal lobe epilepsy, and activation of the complement systemis an important component of this response. Better understanding ofinflammatory changes and correlation with electrophysiological andimaging characteristics may yield insights into the mechanisms underly-ing the development of epilepsy.

Method: Epilepsy was induced by systemic injection of pilocarpine inSwiss mice. Animals were allocated to 3 groups comprising controls(CON, n=6), those with status epilepticus (SE, n=12) following injectionof pilocarpine, and those that did not develop status epilepticus afterinjection (NoSE, n=6). MR images were acquired at 7 and 35 days afterinjection. The MR T2 relaxation times and apparent diffusion coefficient(ADC) maps were compared between the groups using voxel-based sta-tistical parametric mapping. Spontaneous recurrent seizures were quanti-fied with 3 week-long continuous video-EEG monitoring. Complementexpression and glia activation were studied by immunocytochemistry at7 days and 4 months post-SE.

Result: SE group developed chronic recurrent seizures with a frequencyof 0.5 sz/day. No EEG changes were observed in CON or NoSE group.Marked upregulation of complement C3 expression was found in reactiveastrocytes in the hippocampus of SE group, but not in NoSE animals.Compared to NoSE group, SE mice had increased ADC and T2 values inthe hippocampus corresponding to the areas of astrocyte activation andC3 upregulation.

Conclusion: Persistent C3 upregulation following an epileptogenicinsult is associated with destabilization of neuronal networks involved inseizure generation and progression of tissue damage.

008GABAERGIC INTERNEURONS LEAD TO THE EPILE-PTOGENESIS: INTERNEURON PATHOLOGY ASSOCI-ATED WITH ARX MUTATIONM. Itoh*, S. Okazaki�, H. Kawawaki�, T. Inoue�, and Y. Goto**National Center of Neurology and Psychiatry, Kodaira, Japan;and �Osaka City General Hospital, Osaka, Japan

Purpose: X-linked lissencephaly with abnormal genitalia (XLAG),showing severe neonatal seizure and developmental delay, is a rare disor-der caused by mutations in the aristaless-related homeobox (ARX) gene,located in Xp22.13. Arx-null mice for human XLAG model showed lossof tangential migration of GABAergic interneurons. However, GABAer-gic interneuron distribution of XLAG brain has never been reported. Inthe present study, we investigated subpopulation of GABAergic interneu-rons in the brain of an infant with XLAG, who had a nonsense mutationof the ARX gene, compared with those of age-matched normal controland Miller-Dieker syndrome.

Method: We performed immunocytochemistry for interneuron andmigration markers.

Result: Glutamic acid decarboxylase (GAD)- and calretinin (CR)-con-taining cells were significantly very few in the neocortex and, interest-ingly, located in the white matter and neocortical subventricular zone,while neuropeptide tyrosine and cholecystokinin positive cells were nor-mal. From previous rodent studies, the imbalance of GABAergic inter-neurons may be derived from the caudal ganglionic eminence tangentialmigration. Also, in the neocortical subventricular region, the GAD- andCR-containing cells had Mash-1 protein, like a radial migration marker,and nestin protein.

Conclusion: ARX protein controls not only tangential migration ofGABAergic interneurons from the ganglionic eminence, but alsomay serve to induce radial migration from the neocortical subven-tricular zone.

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Clinical EpileptologyMonday, 01 October 2012

009NEUROLOGICAL AND NEUROIMAGING OUTCOMESOF CHILDHOOD STATUS EPILEPTICUS: A 10-YEARCOHORT STUDYS. Pujar*, M. Martinos*, K. Chong�, B. Neville*, R. Scott*, andR. Chin**UCL Institute of Child Health, London, UK; and �GreatOrmond Street Hospital for Children NHS Trust, London, UK

Purpose: The long-term outcome following childhood convulsive statusepilepticus (CSE) is uncertain. We report preliminary data on neurologi-cal and neuroimaging outcomes within 10 years of CSE from a prospec-tive paediatric population-based study.

Method: Enrolled children were invited to have clinical neurologicalevaluation and brain MR Imaging (MRI) on a 1.5T scanner. An experi-enced paediatric neuroradiologist qualitatively assessed all MRIs.

Result: 72 children (33 male) have been investigated. Median follow-up7.9 years. 49 had both clinical assessment and MRI. 20 had prolongedfebrile seizures (PFS), 8 acute symptomatic (AS), 11 remote symptom-atic (RS), 6 idiopathic, and 4 unclassified CSE. At follow-up, all childrenwith PFS were neurologically normal and none had epilepsy. One withAS CSE (12%) developed epilepsy that remitted after 2 years. All withRS CSE, except two, had active epilepsy, and significant neurologicalimpairments. None with idiopathic and unclassified CSE had epilepsy orneurological impairments except two (33%). Only one child (5%) in PFSgroup had abnormal MRI: unilateral reduction in hippocampal volume.Amongst AS CSE, 4 (50%) had normal MRI, 3 (37%) abnormalities unli-kely to be clinically significant, and 1 (12%) had left mesial temporalsclerosis (MTS). The child with MTS had only one episode of CSE withmeningitis and no further seizures. 8 children (73%) with RS CSE hadabnormal MRIs. All children with idiopathic and unclassified CSE hadnormal MRI.

Conclusion: Children without prior neurological insult and/or epilepsyhave good neurological outcome within 10 years of CSE. Significance ofthe hippocampal abnormalities in three children without a clinical corre-late is uncertain.

010ASSESSMENT OF STATUS EPILEPTICUS AND SEI-ZURES IN NEUROLOGICAL INTENSIVE CARE UNITIN SALZBURG, AUSTRIAJ. Dobesberger, A. Arkhundova, H. Novak, A. Zerbs, T. Moroder,J. Hçfler, M. Leitinger, C. A. Granbichler, and E. TrinkaParacelsus Medical University, Salzburg, Austria

Purpose: Status epilepticus (SE) as well as aggravation of epileptic sei-zures (SZs) are common reasons for admission to a neurological intensivecare unit (NICU). They may also occur as complications during the stayin patients at the NICU. The aim of this study was to evaluate incidenceand clinical data of SE and SZs at a NICU.

Method: We retrospectively analysed all consecutive patients who wereadmitted to the NICU of the Department of Neurology, Paracelsus Medi-cal University, in Salzburg, Austria, between from January 2010 to May2011.

Result: A total of 719 patients were admitted to the NICU, 121/719(16.8%) patients (68 men; mean age 59.0 € 19.6 years; range 14–91) hadSE or SZs: 84/121 (69.4%) had the referral diagnosis ‘‘SE’’, 32/121(25.5%) ‘‘SZs’’ and 5/121 (4.1%) developed SE or SZs during the stay.116/119 (97.5%) patients had symptomatic aetiology: acute symptomatic

in 43/119 (36.1%), remote symptomatic in 49/119 (41.2%) and progres-sive symptomatic in 24/119 (20.2%) patients. In acute and remote symp-tomatic aetiology, the most common reasons were cerebrovasculardiseases (14/119; 11.8% vs. 27/119; 22.7%), while in progressive symp-tomatic aetiology brain tumors (8/119; 6.7%) were the most frequentcause. 70/119 (58.5%) patients suffered from epilepsies before admissionto the NICU.

Conclusion: About a sixth of patients admitted to the NICU had SE orSZs. Aetiology was symptomatic in most of the cases. The main reasonsfor acute and remote symptomatic SE or SZs were cerebrovascular dis-eases. Approximately two fifth of the patients had new-onset SZs or SE.

011MIDDLE SHORT GYRUS OF THE INSULA IMPLI-CATED IN SPEECH PRODUCTION: INTRACEREBRALELECTRIC STIMULATION OF PATIENTS WITH EPI-LEPSYA. Afif, L. Minotti, P. Kahane, and D. HoffmannNeurological Hospital, Hospices Civils de Lyon, Lyon, France

Purpose: The data of this study suggests the involvement of the uppermiddle short gyrus in speech production.

Method: 25 patients suffering from severe drug refractory partial epi-lepsy were investigated by stereo-electroencephalography (SEEG). Atleast one electrode explore the insula using an oblique approach (trans-frontal or trans-parietal). 313 stimulations were performed in 27 insula.83 responses induced by insular electrical stimulation (ES), eight (9.6%)were reported by five patients as speech arrest (5 responses) and a lower-ing of voice intensity (3 responses). The stereotactic approach allows usto identify the stimulation sites within the insula in terms of its gyri. Also,the stimulation sites were anatomically localized via image fusionbetween pre-implantation 3D MRI and post-implantation 3D CT scansrevealing the electrode contacts.

Result: 8 responses were reported as speech disturbances. 7 among themwere evoked by stimulation in the middle short gyrus (25.9% ofresponses evoked in the middle short gyrus). The site of the 8th responsewas in the post-central insular gyrus in the same insular region where theoropharyngeal responses induced by other ES (pharyngeal construction)in this study. The data suggest the involvement of the middle short gyrusof the insula in the procedures of language.

Conclusion: This study provides evidence that the middle short gyrus ofthe insula responds to ES producing speech disturbances. These resultsare the first to report language disorders in humans evoked by electricalstimulation of the insular cortex during SEEG explorations in terms ofgyral anatomy.

012ASPECTS OF ICTAL CONSCIOUSNESS IN PATIENTSWITH EPILEPSY, NON-EPILEPTIC ATTACK DISOR-DER (NEAD) AND DUAL DIAGNOSISA. E. Cavanna, and F. AliBirmingham and Solihull Mental Health NHS Foundation Trust,Birmingham, UK

Purpose: Self-report measures of ictal consciousness suggest greaterlevels of awareness and subjective experiences in patients with NEADcompared to epilepsy. This study further investigated which specificaspects of consciousness alterations show most variability across seizuretypes.

Method: A total of 77 adult out-patients (n=21 with a diagnosis of epi-lepsy, n=38 with NEAD and n=17 with a dual diagnosis) were recruited

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from the specialist Neuropsychiatry Clinic at BSMHFT/University ofBirmingham. All participants completed a standardised battery of psy-chometric measures, including the 20-item Ictal Consciousness Inventory(ICI). This instrument allows investigation of the level of awareness(ICI-level: items 1–10) and subjective consciousness experiences (ICI-content: items 11–20) during recalled seizures and non-epileptic attacks.

Result: Item-by-item comparison revealed a statistically significant dif-ference in Item 20, which captures the presence and vividness of ictalemotions (Kruskall-Wallis test, p=0.05; epilepsy mean score=3.6;NEAD= 4.2; dual diagnosis=3.3). Trends towards statistical significancewere also demonstrated for Item 17, which assesses metamorphopsia(p=0.08; dual diagnosis mean score=4.2; epilepsy=3.3; NEAD=4.0) andItem 18, which assesses mnestic dysperceptions (p=0.09; epilepsy meanscore=3.2; NEAD=4.0; dual diagnosis=4.2).

Conclusion: The results of the present study are in accordance with pre-vious findings, emphasizing the more florid interpretation of ictal experi-ences in patients with NEAD. This is particularly evident in itemsassessing the presence of positive ictal emotions, metamorphopsia andmemory flashbacks, suggesting a possible role for dysregulation in theemotional processing of perceptual experiences in the pathophysiologyof NEAD.

NeuropsychiatryMonday, 01 October 2012

013POSTICTAL PSYCHOSIS IN TEMPORAL LOBE EPI-LEPSY – RISK FACTORS AND POSTSURGICAL OUT-COMER. A. Cleary*, P. J. Thompson*, and J. Foong�

*The National Hospital for Neurology and Neurosurgery andInstitute of Neurology, London, UK; and �The National Hospitalfor Neurology and Neurosurgery, London, UK

Purpose: Postictal psychosis (PIP) reportedly occurs in 4–10% ofpatients with temporal lobe epilepsy (TLE). Whilst the clinical character-istics are well described, less is known about the pathophysiologicalmechanisms and predisposing factors. The aims of this study were toidentify risk factors that may predispose patients to developing PIP andto determine whether a history of PIP predicts postsurgical outcome.

Method: We identified 20 patients with a history of PIP-TLE from atotal of 280 TLE patients on the epilepsy surgery database at the NationalHospital for Neurology and Neurosurgery, London. They were comparedto 60 age-matched TLE patients without any psychiatric history, withrespect to presurgical clinical and neuropsychological variables. Groupdifferences in postsurgical psychiatric, cognitive and seizure outcomesover 4 years were also examined.

Result: Our current analysis indicated that PIP-TLE patients were lesslikely to have localised interictal and ictal EEG abnormalities than theTLE controls, particularly regarding ictal EEGs. Other presurgical clini-cal and neuropsychological variables did not distinguish between thegroups. PIP-TLE patients were more likely to develop postsurgical psy-chiatric disorders (p=0.018) within 4 years of surgery but there were nodifferences in seizure or cognitive outcomes.

Conclusion: Our results suggest that more widespread or diffuse brainabnormalities as reflected by EEG findings may contribute to the devel-opment of PIP. Furthermore, patients with a history of PIP who undergoepilepsy surgery have an increased risk of developing postsurgical psy-chiatric disorders. This has implications for presurgical counselling andalso highlights a need for postsurgical psychiatric monitoring for thesepatients.

014PSYCHIATRIC COMORBIDITY IN CHILDRENBEFORE AND AFTER TEMPORAL LOBE EPILEPSYSURGERYA. Michoulas*, C. Waisburg�, S. J. Akdag�, A. Chapman§, andM. B. Connolly**University of British Columbia, BC Children's Hospital,Vancouver, Canada; �Institue of Neurosciences, FavaloroUniversity, Buenos Aires, Argentina; �BC Children's Hospital,Vancouver, Canada; and §University of British Columbia, BCChildren's Hospital, Vancouver, Canada

Purpose: The primary objective of this study was to establish the rateand types of psychiatric comorbidities among children with temporallobe epilepsy before and after epilepsy surgery. The secondary objectivewas to examine for predictors of psychiatric comorbidity.

Method: All pediatric patients who underwent temporal lobe epilepsysurgery at British Columbia Children's Hospital between 1995 and 2010,with a minimum 12 month follow-up were included. Sixty-three chartswere retrospectively reviewed. Patients undergo multidisciplinary evalu-ation including screening and referral for psychiatric symptoms. Psychi-atric disorders included: attention-deficit/hyperactivity disorder(ADHD), emotional disorder (depression and/or anxiety), pervasivedevelopmental disorder (PDD), obsessive-compulsive disorder and psy-chosis.

Result: Psychopathology was diagnosed in 26 (44.4%) patients pre-operatively and in 31 (49.2%) patients post-operatively. The most com-mon were emotional disorder (27% pre-operative and 36% post-opera-tive) and ADHD (26% pre-operative and 20% post-operative). Notably,58% of patients with an emotional disorder received psychological and/or medical therapy. Five of 17 (29.4%) patients with depression had sui-cidal ideation. Pre-operative ADHD was significantly more common inpatients with a family history of psychiatric illness (p=0.002). Pre-opera-tive psychiatric comorbidity was a significant predictor of post-operativepsychiatric comorbidity, p=0.006. No relationship was found betweenduration of epilepsy, pathology, seizure outcome and psychiatric diagno-sis.

Conclusion: Psychiatric comorbidity is common in pediatric temporallobe epilepsy. Temporal lobe surgery did not influence the occurrence ofpost-operative psychopathology. Children with a pre-operative psychiat-ric comorbidity were significantly more likely to have a post-operativepsychiatric comorbidity. Psychiatric assessment and treatment are impor-tant components of epilepsy surgery care.

015HOW SODIUM VALPROATE CAUSES LANGUAGEDELAY AND AUTISM - A MOLECULAR STUDYR. Moldrich, G. Leanage, and D. ReutensUniversity of Queensland, Brisbane, Qld, Australia

Purpose: The widely used anti-epileptic drug sodium valproate (VPA)vastly increases the risk of autism spectrum disorders (ASD) upon prena-tal exposure. Our aim was to test the hypothesis that VPA is causing ASDvia inhibition of histone deacetylase (HDAC) using a mouse model of inutero VPA exposure.

Method: We created an mouse model of autism prenatally exposed toVPA (600mg/kg) at embryonic day 12 and compared it to an animal pre-natally exposed to a specific HDAC inhibitor, trichostatin A (TSA)(1mg/kg). We measured HDAC enzyme activity, histone acetylation sta-tus and behavioural features in juvenile mice.

Result: Treatments with 600 mg/kg VPA and 1 mg/kg TSA reducedHDAC enzyme activity to activity to 60% and 63% of control, respec-tively. We also measured acetylated histone levels by SDS-PAGE and

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Western blot. We found that 600 mg/kg VPA, 200 mg/kg VPA and 1 mg/kg TSA similarly increased acetylated histone H4, but not H3 levels toapproximately 200% of control. Postnatally, 600 mg/kg VPA and 1 mg/kg TSA treated mice demonstrated a similar lack of olfactory motivation,delayed motor ability and sociability deficits, analogous to deficits seenin infants with autism.

Conclusion: Pharmacological or environmental inhibition of HDACcan lead to subtle morphological changes in the developing embryo, lead-ing to ASD-like behavioural manifestations. Further, HDAC inhibition inembryos is likely the cause of developmental delay following VPAadministration during pregnancy.

016PREVALENCE AND ASSOCIATES OF SUICIDALBEHAVIOR IN FREQUENT TREATMENT-RESISTANTFOCAL SEIZURES: THE ASERT STUDYJ. French*, D. Hesdorffer�, K. Posner�, B. Diventura*,J. Pollard�, M. Sperling§, C. Harden–, G. L. Krauss**, andA. M. Kanner��

*New York University Comprehensive Epilepsy Center, NewYork, NY, USA; �Columbia University, New York, NY, USA;�University of Pennysilvania, Philadelphia; §Thomas JeffersonUniversity, Philadelphia; –Long Island Jewish Medical Center,North Shore; **Johns Hopkins University, 21287 USA; and ��

Rush Medical College, Chicago, USA

Purpose: To assess lifetime suicidal ideation (SI) and behavior (SB),and their associates in treatment-resistant focal seizures.

Method: A mulitcenter, cross-sectional study at 6 epilepsy centers.Inclusion criteria were: 18–70 years; EEG-confirmed focal epilepsy for>2 years; >1 simple partial (with motor component), complex partial/sec-ondarily generalized seizure per month for the past 6 months; currentlytaking 1–3 AEDs; and failed >2 AEDS, including current therapy.Columbia Suicide Severity Rating Scale assessed SI/SB. MINI assessedmajor depression (MD). High risk SI included intent/intent and plan. SBincluded suicide attempt (SA), interrupted or aborted attempt, prepara-tory acts/behavior, and non-suicidal self-injurious behavior. Calculatedfrequency of lifetime SI/SB. Logistic regression examined demographic,seizure-related and psychiatric correlates of suicidality.

Result: 95 of 206 participants (46.1%) had lifetime SI, 29 (14.1%) hadhigh risk SI, 21 (10.2%) had SA and 21 (10.2%) had SB without SA. Nodemographic or seizure-related factors were associated with SI or SB.Lifetime MD was significantly associated with lifetime SI (OR=10.8),high risk SI (OR=4.7), SA (OR=4.7) and SB without SA (OR=4.9).

Conclusion: SB without SA is as common as SA alone in treatment-resistant focal seizures. Only lifetime MD is associated with SI/SB. Pre-vention of SB in epilepsy requires identification of lifetime MD in orderto counsel and offer treatment.

Antiepileptic DrugsMonday, 01 October 2012

017ANALYSIS OF EFFICIENCY AND SAFETY OF OX-CARBAZEPINE DEPENDING ON PATIENT'S AGE ANDFORMS OF EPILEPSYA. A. Kholin*, E. S. Il`Ina�, and N. N. Zavadenko**Russian State Medical University, Moscow, RussianFederation; and �Russian Children Clinical Hospital, Moscow,Russian Federation

Purpose: The aim of the study was analysis of efficiency and safety ofoxcarbazepine at children and adults depending on patient's age andforms of epilepsy.

Method: 155 patients receiving oxcarbazepine (male = 78, female = 77)of the age from 5 month till 59 years are observed in dynamics withvideo-EEG control at the period 2006–2011. Were identified: IGE withisolated GTCS 5, focal frontal lobe epilepsy 40, temporal lobe 63, parie-tal lobe 6, occipital lobe 13, idiopathic focal 5, epileptic encephalopathies– 23 patients.

Result: Oxcarbazepine was effective at 59.3% of patients (n=92), andamong the patient at monotherapy effectiveness (68.5%, at 37 from 54patients) was higher than in combined therapy (54.4% at 55 of 101patients). Low efficiency was seen at 29.1% (n=45) patients. Theaggravation effect has been noted at 11.6% (n=18) of patients. Drugcompliance (for >1 year) was 56.8% (n=88). High efficiency in group<1 year (n=14) was 35.7% (n=5), low 35.7% (n=5), aggravation 28.6%(n=4); in group 1–3 years (n=24) high efficiency 37.5% (n=9), low37.5% (n=9), aggravation 25% (n=6); in pediatric population >3 years(n=78) high efficiency 62.8% (n=49), low effect in 29.5% (n=23), and7.7% aggravation (n=6), in adult population >18 years (n=39) the effi-ciency was 74.4% (n=29), low effect 20.5% (n=8) and aggravation in5.1% (n=2).

Conclusion: Oxcarbazepine is highly effective drug in therapy of IGEwith isolated GTCS, in symptomatic focal forms and Panayiotopoulossyndrome. With increasing of patients age the efficiency of oxcarbaze-pine raises, while aggravation risks decrease.

018DISCONTINUATION OF ANTIEPILEPTIC DRUGS INPREGNANCY: A UK POPULATION BASED STUDY INTHE HEALTH IMPROVEMENT NETWORK PRIMARYCARE DATABASES. Man*, I. Petersen*, M. Thompson�, and I. Nazareth**University College London, London, UK; and �CegedimStrategic Data, London, UK

Purpose: Antiepileptic drugs (AEDs) control seizures, which is a prior-ity in pregnancy to prevent harm to the mother and fetus. However, AEDsare associated with increased risk of congenital malformations. Weexamined the discontinuation of AED prescribing in pregnant womenusing UK primary care data from The Health Improvement Network.

Method: In total, 174,055 pregnant women were identified aged 13–55 years of which 745 were prescribed AEDs for epilepsy in thethree months before pregnancy. Time to the last consecutive AEDprescription before delivery was estimated and comparisons made tonon-pregnant women with epilepsy, using Cox's regression. Factorspredicting discontinuation of AEDs amongst pregnant women wereinvestigated.

Result: Pregnant women with epilepsy were twice as likely to ceaseAEDs compared to non-pregnant women (Hazard Ratio (HR):2.00,95% confidence interval (CI):1.62–2.47). Of 745 women, 601 (80.7%)continued treatment into pregnancy and 465 (62.4%) to the end of thesecond trimester. Of 1490 non-pregnant women with epilepsy, 1242(83.4%) and 1071 (71.9%) continued for comparable time periods.Compared to pregnant women with more than one AED prescribed in3–6 months before pregnancy, women with one prescription were morelikely to cease treatment (HR: 3.31, 95% CI: 2.57–4.23), whilst thosewith no prior prescriptions were at an even higher risk (HR: 6.32, 95%CI: 4.57–8.73).

Conclusion: Pregnancy is a determinant for the discontinuation of AEDprescribing amongst women with epilepsy, despite the possible graveconsequences of uncontrolled seizures in pregnancy. Women with littleexposure to AEDs prior to pregnancy should be monitored closely toensure they do not abruptly cease medication.

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019TOLERABILITY AND SAFETY OF ZONISAMIDE INELDERLY PATIENTS WITH PARTIAL EPILEPSY:RESULTS OF A POOLED ANALYSISE. Trinka*, J. Segieth�, and L. Giorgi�

*Paracelsus Medical University, Salzburg, Austria; and �EisaiLimited, Hatfield, UK

Purpose: To assess the tolerability/safety of zonisamide in elderlypatients with partial epilepsy.

Method: A pooled analysis of data from elderly (‡65 years) patientsreceiving zonisamide for partial seizures in clinical studies was con-ducted (N=95) and compared to pooled adult (18–65 years) patient data(N=1389). Assessments included treatment-emergent adverse events(TEAEs), clinical laboratory parameters and weight.

Result: Overall incidence of TEAEs was similar in elderly versus adultpatients (82.1% vs. 83.9%). Incidence was lower in elderly versus adultpatients for treatment-related TEAEs (55.8% vs. 72.7%), severe TEAEs(11.6% vs. 20.4%), serious TEAEs (12.6% vs. 16.6%), and TEAEs lead-ing to withdrawal (17.9% vs. 22.1%). TEAEs reported by ‡5% of patientsin either cohort and more frequently by elderly versus adult patients werefatigue (11.6% vs. 9.7%), nasopharyngitis (8.4% vs. 7.2%), constipation(7.4% vs. 4.8%) and pruritus (6.3% vs. 2.1%). Serious TEAEs reportedby >2% elderly patients were convulsion (2.1%) and grand mal convul-sion (2.1%). Three elderly patients died but only one death was consid-ered treatment-related (circulatory collapse following pancreatitis). Nosevere TEAEs were reported by >2% elderly patients. For elderlypatients, there were few clinically significant changes in clinical labora-tory parameters, no reports of respiratory alkalosis or metabolic acidosis,and no significant weight changes.

Conclusion: Zonisamide was well tolerated by elderly patients with par-tial epilepsy when compared to adult patients. Most TEAEs were ofmild-to-moderate intensity and the overall incidence was similar to adultpatients. No new or unexpected safety findings were identified.Supported by Eisai

020LONG-TERM TREATMENT WITH ADJUNCTIVE LA-COSAMIDE FOR PARTIAL-ONSET SEIZURES: ANANALYSIS OF RESULTS FROM PATIENTS EXPOSEDONLY TO APPROVED DOSESN. Dcruz*, P. Doty*, C. Mcshea*, S. Dimova�, and M. DeBacker�

*UCB, Raleigh, USA; �UCB Pharma, Brussels, Belgium; and�UCB, Brussels, Belgium

Purpose: To evaluate long-term efficacy and tolerability of adjunctivelacosamide in adults with partial-onset seizures (POS) who received laco-samide doses within the approved dose range (£400mg/day).

Method: Data were pooled from three long-term, open-label extensiontrials (OLE; NCT00552305; NCT00522275; NCT00515619) in adultswith POS who had completed one of three double-blind, placebo-con-trolled Phase II/III trials of adjunctive lacosamide. During OLE treat-ment, dosage adjustments of lacosamide (100–800mg/day) and/orconcomitant AEDs were allowed to optimize tolerability and seizure con-trol. This subanalysis evaluates trial outcomes during the extension studyfor patients exposed to £400mg/day lacosamide during both double-blindand open-label treatment.

Result: Of 1,054 patients who initiated open-label lacosamide treat-ment, 363 (34.4%) had been exposed only to lacosamide doses £400mg/day. Patients exposed to £400mg/day lacosamide for >1, >2, >3, >4 and>5 years was 64.2%, 50.1%, 41.0%, 34.2%, and 15.7%; the decrease after

3 years’ exposure was due to premature discontinuations and study com-pletion because of the commercial availability of lacosamide. For 1-year,2-year, 3-year, 4-year and 5-year completers, the median percent seizurefrequency reduction from Baseline was 59.4%, 64.1%, 67.9%, 69.3%and 71.0%; the ‡50% responder rate was 60.2%, 65.9%, 68.0%, 72.6%and 70.2%. A total of 81.3% of patients reported ‡1 treatment-emergentadverse event, most commonly (‡10%) dizziness (21.5%), headache(14.0%), and nasopharyngitis (10.7%).

Conclusion: Used in the approved dose range (up to 400mg/day), long-term adjunctive lacosamide provided sustained efficacy and was well tol-erated in adults with POS. These subanalysis results are consistent withthose for the entire OLE population. UCB-sponsored.

Clinical Pharmacology and TherapeuticsTuesday, 02 October 2012

021ANTIEPILEPTIC DRUGS AND LIPID METABOLISM:VALPROATE NOT SO INNOCENT?I. Y. Tan, H. Hegge, M. Majoie, P. Verschuure, C. Vader, andM. VeendrickKempenhaeghe, Heeze, The Netherlands

Purpose: Following the hypothesis that Antiepileptic Drugs (AED)influence lipid metabolism via the cytochrome P450 system, we studiedthe relation between drugload of enzyme-inducers (IND_AED) andenzyme-inhibitors (INH_AED) on the one hand and lipid fractions on theother hand in adult patients with polytherapy.

Method: Blood samples were collected from 261 resident patients of anepilepsy center, who all had epilepsy and (intellectual) disability. Patientswith interfering medication were excluded. Patients were groupedaccording to use of IND_AED (87 patients with carbamazepine, phenyt-oin and/or phenobarbital) or INH_AED (20 patients using valproate).Enzyme-neutral comedication was allowed. Assessment was done forlipid metabolism, including Cholesterol, High-density lipoproteins(HDL), Low-density lipoproteins (LDL), triglycerides (TG) and TotalCholesterol (TC). Drug load was computed by summing PDD/DDDs(Prescribed daily dose/defined daily dose) for AED in the same ‘‘enzyme-group’’.

Result: Not surprisingly, IND_AED correlated with higher levels ofserum lipids LDL, HDL, TG and TC. This is consistent with evidencefrom literature. Higher drugload of IND_AED correlated with higherlipid fractions, but this effect just failed to reach statistic significance.Remarkably, INH_AED correlated with elevated levels of TG, which toour knowledge is a novel finding. Moreover, there was a statistic signifi-cant relation between drugload of INH_AED and TG and TC/HDL ratio.A possible explanation for this phenomenon is that the elevated TG levelsare an expression of a metabolic syndrome, related to VPA. A remarkableanecdotic finding was that in one of the patients on valproate the TG leveldecreased considerably after discontinuing valproate.

022DOES CARBAMAZEPINE AFFECT THE QT INTER-VAL?T. Yadee, and K. UnnwongsePrasat Neurological Institute, Bangkok, Thailand

Purpose: Pathologic cardiac repolarization may occur during seizuresand has been linked to SUDEP. In this retrospective case control study,we investigated if Carbamazepine affects the QTc interval.

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Method: Nineteen patients with epilepsy on Carbamazepine werematched for age and sex to 19 patients on Carbamazepine for neuralgia ormood disorders and 19 patients admitted for elective surgeries who werenot taking Carbamazepine. None of the patients had concomitant cardio-vascular disease or were taking medications known to affect the QTcinterval. QTc intervals and Carbamazepine doses and blood levels, wereanalyzed using one-way ANOVA.

Result: Two out of 19 patients (11%) in the epilepsy group but nonein other groups had QTc prolongation (>450 milliseconds). The meanQTc interval was longer in patients taking Carbamazepine for epilepsy,compared to both patients taking Carbamazepine for other reasons andpatients without epilepsy not taking Carbamazepine (417€26 vs400€17 vs 403€16 milliseconds) (p=0.029). Mean dose and blood levelof Carbamazepine in epilepsy and non-epilepsy groups did not differ(737€389vs 716€407 mg/d and 7.27€2.46vs 7.36€2.65 mg/dl) (p=0.87and p=0.92).

Conclusion: Carbamazepine may lead to QTc prolongation in patientswith epilepsy but not in other neurologic disorders. A longitudinal studycomparing QTc intervals before and after treatment with Carbamazepineis required to confirm this finding.

023CHANGED CONSTITUTION WITHOUT CHANGE INBRAND NAME - THE RISK OF GENERICS IN EPILEPSYV. I. Patel, D. J. Cordato, M. Dias, and R. G. BeranLiverpool Hospital, Liverpool, NSW, Australia

Purpose: Lamotrigine (LTG) is an Anti Epileptic Medication (AEM)for which blood levels are helpful for optimal dosing. In late 2010,patients attending an epilepsy clinic were becoming toxic without obvi-ous cause. This paper reports altered levels without change in regimenand provides unexpected findings.

Method: Patients with elevated LTG blood levels were assessed todetermine change in AEM regimen or generic substitution. Method ofblood level determination was reviewed and the company (Glaxo-SmithKline) contacted regarding change in source of medication.

Result: The sample comprised 18 patients; mean age 40 € 16 years,mean daily LTG dose 493 € 218 mg. Mean serum LTG concentrationsfrom August 2010 to February 2011 [91.8€17.7 lmol L-1, range 69.9–133.7 lmol L-1] were significantly higher than those from January 2010to July 2010 [50.3€9.1lmol L-1, range 32–60.1 lmol L-1), p < 0.0001].All patients received parent product (Lamictal�) and the method of LTGblood level determination was unchanged. GlaxoSmithKline confirmedthat Lamictal� was sourced from a different site.

Conclusion: These results indicate that, even using a parent compound,AEM levels can fluctuate if the product source has changed, resulting intoxicity. It also highlights the value of determining AEM levels and therisks attached to generic substitution.

024ONE YEAR FOLLOW-UP EXPERIENCE WITH ES-LICARBAZEPINE ACETATE (ZEBINIX�) IN A TER-TIARY HOSPITAL IN OPORTO, PORTUGALF. D. Correia, J. P. Domingos, J. G. Freitas, R. Loureiro,J. Lopes, J. Ramalheira, J. Chaves, and J. Lopes-LimaHospital de Santo Ant�nio, Centro Hospitalar do Porto, Porto,Portugal

Purpose: Introduction: Eslicarbazepine acetate (ESL) is a new antiepi-leptic drug available in Portugal since April 1st 2010. Despite good safetyand efficacy shown in clinical trials, little is known about its effectivenessin clinical practice. Objective: Assess one year follow-up post-commer-cialization experience

Method: All outpatients who initiated treatment with ESL between 01/04/2010 and 31/03/2011 were included. We retrospectively collecteddata on demographics, clinical features, treatment response, complianceand side effects. Only patients with at least one follow-up (FU) visit wereincluded in the safety analysis, and only those with ‡1 year follow-upwere included in the effectiveness analysis.

Result: We included 113 patients (58$), mean age 39yo (7–76), meanepilepsy duration 27.2 years (2–50) and mean seizure frequency 27/month (0–600); 57.5% were taking £2 AED and the remaining ‡3 AEDs.At the last FU visit (n=110), 71.8% were still on treatment [median dos-age 1200mg (400–1600)]. Therapy discontinuation was mainly due toside effects (17.7%) or lack of efficacy (7.1%). About 49% of patients(n=56) had ‡1 year follow-up. From these, 38.2% were responders(‡50% reduction in seizure frequency); 39.3% were greatly improved orseizure free (clinician global impression-CGI). Effectiveness was higherin patients treated with £2 AEDs vs ‡3 AEDs (Responder rate - 46.7% vs28.0%, p=0.254; CGI - 51.6% vs 24.0%, p=0.068).

Conclusion: In a one year FU, ESL was effective in a significant propor-tion of patients particularly in those with less refractory epilepsy. ESLwas well tolerated, with few patients discontinuing drug due to sideeffects, none of which severe.

Genetics 2Tuesday, 02 October 2012

025PRRT2 LINKS INFANTILE CONVULSIONS AND PAR-OXYSMAL DYSKINESIA WITH MIGRAINER. Cloarec*, N. Bruneau*, G. Rudolf�, A. Massacrier*,M. Salmi*, M. Bataillard�, C. Boulay�, R. Caraballo�,N. Fejerman�, P. Genton*, E. Hirsch�, A. Hunter§, G. Lesca–,J. Motte**, A. Roubertie��, D. Sanlaville–, S. W. Wong��, Y. Fu§§,J. Rochette––, L. Ptacek§§, and P. Szepetowski**INSERM U901 - INMED, Marseille, France; �StrasbourgUniversity Hospital, Strasbourg, France; �Juan P. GarrahanPediatric Hospital, Buenos Aires, Argentina; §Children'sHospital of Eastern Ontario, Ottawa, Canada; –UniversityHospital of Lyon, Bron, France; **American MemorialHospital, Reims University Hospital, Reims, France; ��

Montpellier, France; ��Universiti Kebangsaan Malaysia, KualaLumpur, Malaysia; §§University of California San Francisco,San Francisco, USA; and ––Universit� de Picardie Jules Verne,Amiens, France

Purpose: Whole genome sequencing and the screening of 103 familiesrecently led us to identify PRRT2 (proline-rich transmembrane protein)as the gene causing autosomal dominant infantile convulsions (IC) withparoxysmal kinesigenic dyskinesia (PKD) (PKD/IC syndrome, formerlyICCA). There is inter- and intra-familial variability and the patients maypresent with IC and/or PKD. In order to explore the mutational and clini-cal spectra, additional cases and families with either typical PKD/IC orPKD/IC with migraine were analyzed.

Method: Sanger sequencing of all PRRT2 coding exons and of exon-intron boundaries was performed in the probands and in their relativeswhenever appropriate.

Result: PRRT2 mutations were detected in 18 of 34 families. Thep.R217Pfs*8 recurrent mutation and a novel frameshift mutation(p.R145Gfs*31), were found in 50% of typical PKD/IC. In another fam-ily, p.R217Pfs*8 cosegregated with PKD associated with hemiplegicmigraine (HM). p.R217Pfs*8 was also detected in one IC patient havingmigraine with visual aura and speech difficulties, and in related PKD/ICfamilial cases having migraine without aura. p.R217Pfs*8 was alsodetected in one sporadic case with complex migrainous disorder. The pre-

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viously reported p.R240X mutation was found in one PKD patient withmigraine without aura. A novel frameshift mutation (p.S248Afs*65) wasidentified in a PKD/IC family member with IC and migraine with visualand aphasic aura.

Conclusion: Taken together, our data extend the spectrum of PRRT2mutations and phenotypes to HM and to other types of migraine in thecontext of PKD/IC, and emphasize the phenotypic pleiotropy seen withPRRT2 mutations.

026THE FAMILIAL EPILEPSY SYNDROME OF GENETICEPILEPSY WITH FEBRILE SEIZURES PLUS: SYN-DROME EVOLUTION OVER SEVENTEEN YEARSI. E. Scheffer*, J. P. Malone�, G. C. Glubb�, K. Helbig�,L. Dibbens�, L. Vadlamudi�, A. Bleasel§, R. Burgess�,B. Grinton�, D. Vears�, Z. Afawi–, H. Goldberg-Stern**,S. Kivity**, A. D. Korczyn–, J. Mulley��, S. Berkovic�, andY. H. Zhang�

*Royal Children's Hospital, Parkville, Vic., Australia; �

University of Melbourne, Melbourne, Vic., Australia; �Women'sand Children's Hospital, North Adelaide, SA, Australia;§Westmead Hospital, Westmead, NSW, Australia; –SacklerFaculty of Medicine, Tel Aviv University, Tel Aviv, Israel;**Schneider Children's Medical Center of Israel, Petach Tikva,Israel; and ��University of Adelaide, Thebarton, SA, Australia

Purpose: GEFS+ (generalised epilepsy with febrile seizures plus) isa familial epilepsy syndrome characterized by phenotypic heterogene-ity that we described in 1997. The GEFS+ spectrum includes FebrileSeizures (FS), Febrile Seizures Plus (FS+), FS/FS+ with generalisedand focal seizures, and a range of epileptic encephalopathies includ-ing Dravet syndrome and epilepsy with myoclonic-atonic seizures.GEFS+ is associated with mutations of sodium channel and GABAreceptor subunit genes; in addition, susceptibility genes have beenidentified in smaller families. We studied 31 new families and analy-sed the phenotypic spectrum in these families and our previouslypublished families.

Method: We performed detailed electro-clinical phenotyping on allavailable affected family members and reviewed EEG and neuroimagingstudies. We reported the phenotypic findings on 408 affected individualsin a total of 60 families.

Result: New phenotypes in GEFS+ families included focal seizureswithout preceding FS, classical genetic generalised epilepsies andafebrile generalised tonic-clonic seizures. FS remains the most fre-quent phenotype in GEFS+ followed by FS+. Large GEFS+ familiesare suggestive of autosomal dominant inheritance. Many smallerfamilies exist where the inheritance pattern is more suggestive ofcomplex inheritance.

Conclusion: We suggest that GEFS+ should be renamed ‘‘genetic epi-lepsy with febrile seizures plus’’ in view of the significant number of indi-viduals with focal epilepsies. The overlap between GEFS+ and theclassical genetic generalised epilepsies is considerably greater than firstthought and suggests that the two major groups of generalised epilepsieshave shared genetic determinants.

027PROSPECTIVE STUDY OF POLG1 MUTATIONS PRE-SENTING IN CHILDREN WITH INTRACTABLE EPI-LEPSY-PREVALENCE AND CLINICAL FEATURESJ. Uusimaa*, J. Poulton*, V. Gowda�, T. Mcshane�, C. Smith�,J. Evans�, A. Shrier*, Y. Rajabally�, M. Narasimhan�,A. O’Rourke�, F. Cowan§, and C. Fratter�

*University of Oxford, Oxford, UK; �Oxford University NHSTrust, Oxford, UK; �Leicester Royal Infirmary, Leicester, UK;and §Imperial College, London, UK

Purpose: To assess the frequency and clinical features of childhoodonset intractable epilepsy caused by the most common mutations in thePOLG1 gene which encodes coding for the catalytic subunit of mitochon-drial DNA polymerase gamma.

Method: Children presenting with non-syndromic intractable epilepsyof unknown aetiology, but without documented liver dysfunction at pre-sentation were eligible for the prospective, population-based study. Theblood samples were analysed for the three common POLG1 mutations. Ifsome of the three tested mutations were found, all the exons and theexon-intron boundaries of the POLG1 gene were sequenced. In additionwe retrospectively reviewed the notes of patients presenting with intrac-table epilepsy in whom we had found POLG1 mutations. All availableclinical data was collected by questionnaire and by reviewing the medicalrecords.

Result: We analysed 213 blood DNA samples from patients fulfillingthe inclusion criteria of the prospective study. Among these, four patients(1.9%) were found with one of the three common POLG1 mutations ashomozygous or compound heterozygous states. In addition, three patientswere retrospectively identified. Six out of seven patients had either raisedCSF lactate or brain MRI changes at the presentation of intractable epi-lepsy. Two of the three patients who later developed liver dysfunctiondied.

Conclusion: We recommend POLG1 gene testing for patients withintractable seizures and ‡1 raised CSF lactate or suggestive brain MRIchanges (with thalamic predominance) with or without status epilepticus,epilepsia partialis continua or liver manifestations typical for Alpers dis-ease, especially when the disease course is progressive.

028INFLAMMATORY PROCESS AND MESIAL TEMPO-RAL LOBE EPILEPSY WITH EPILEPSY: THE ROLE OFIL-1bJ. Chaves*, C. Brito�, B. Leal�, C. Carvalho�, A. Bettencourt�,R. Branco�, A. Martins Da Silva�, P. P. Costa�, and B. MartinsDa Silva�

*Hospital de Santo Ant�nio, Centro Hospitalar do Porto, Porto,Portugal; and �Instituto CiÞncias Biom�dicas Abel Salazar,Porto, Portugal

Purpose: Neuroinflammation appears as an important epileptogenicmechanism. Evidence from animal models demonstrated a rapid-onsetinflammatory response to acute seizures involving interleukin-1b (IL-1b). It was reported that a polymorphism (-511 T>C) in the promoterregion of IL-1b gene leads to a higher protein production. The -511Tallele has been well accepted as associated with Febrile Seizures (FS)nevertheless the association with Mesial Temporal Lobe Epilepsy withHippocampal Sclerosis (MTLE-HS) development is still controversial.In this study we proposed to analyse the association between -511T>Cpolymorphism and the development and clinical features of MTLE-HS ina cohort of Portuguese population.

Method: Ninety-four MTLE-HS patients (49F, 45M, meanage=39.16€10.21 years, 49 with FS antecedents), 95 patients with otherfocal epilepsies (OEF) and 217 healthy controls were studied. Genotyp-ing was performed using Taqman Real Time PCR methodology.

Result: The -511T allele frequency was higher in MTLE-HS when com-pared to controls (39% vs. 32%, p=0.06 OR=1.40 [0.99–2.00]). Consider-ing the antecedents of FS we constitute 2 MTLE-HS sub-groups and nodifferences in -511T>C allelic or genotypic frequencies were found.There were no differences between the OEF group and controls orMTLE-HS patients.

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Conclusion: Our data suggests that -511T allele may be a susceptibilityfactor to MTLE-HS, independently of FS antecedents. The exacerbatedinflammatory reaction associated with this allele could lead to cell lossand progression of seizures. These observations must be confirmed in ahigher cohort. Supported by a BICE Tecnifar Grant 2009

NeuropsychologyTuesday, 02 October 2012

029NEUROPSYCHOLOGICAL FUNCTIONING IN PAEDI-ATRIC EPILEPSY SYNDROMESA. F. Lopes*, M. R. Sim�es*, M. J. Fonseca�, J. P. Monteiro�,and C. Robalo�

*University of Coimbra, Coimbra, Portugal; �Hospital Garciade Orta, Almada, Portugal; and �Hospital Pedi�trico deCoimbra, Coimbra, Portugal

Purpose: The aim of the current investigation is to examine neuropsy-chological functioning in common childhood epilepsy syndromes [Fron-tal Lobe Epilepsy (FLE), Absence Epilepsy (AE), Benign Epilepsy withCentro-Temporal Spikes (BECTS)], compare them with matched con-trols and study the influence of epilepsy-related variables.

Method: Neuropsychological status was examined in 90 children withepilepsy (30 FLE, 30 AE, 30 BECTS), aged 6–15 years and comparedwith a control group. Children with epilepsy were selected based on thefollowing inclusionary criteria: (1) FSIQ ‡ 70 (WISC-III), (2) EEG thatconfirmed the diagnosis of epilepsy and (3) were receiving no more thantwo antiepileptic medications. Participants completed the followingtasks: Memory (List Learning, Rey Complex Figure, Corsi), Language(Rapid Naming, Phonological Awareness, Comprehension, Verbal Flu-ency), Attention and Executive Functions (Cancellation Task, Trail Mak-ing Test (Parts A and B), Tower of London).

Result: All epilepsy syndromes showed deficits in language, attentionand executive functions. Children with FLE also scored lower in verbaland visual memory. Earlier age at onset was associated with problems inlong-term visual memory, sustained attention and executive functions.Children with a longer duration of epilepsy were more likely to presentdeficits in sustained attention. Seizure frequency and side of focus didnot influence results.

Conclusion: This study demonstrates cognitive dysfunction in threecommon childhood epilepsy syndromes, especially in FLE. Also, ourresults suggest that age at onset and duration of epilepsy are associatedwith neuropsychological functions outcome. The neurocognitive screen-ing will be an effective tool in assessing those children in risk of schooldifficulties.

030NEUROPSYCHOLOGICAL FUNCTION OF PATIENTSWITH UNVERRICHT-LUNDBORG DISEASEJ. Hyppçnen*, M. �iki*, A. E. Lehesjoki�, and R. Klviinen**Kuopio University Hospital, Kuopio, Finland; and �Universityof Helsinki, Helsinki, Finland

Purpose: Unverricht-Lundborg disease (ULD), an autosomal reces-sively inherited neurodegenerative disorder characterized by action-acti-vated and stimulus-sensitive myoclonus and epileptic seizures. Duringyears some of the patients become severely incapacitated. The aim of thisstudy was to evaluate cognitive function of patients with ULD.

Method: We evaluated cognitive performance of 68 genetically verifiedULD patients (37 M, 31 F), mean age 35 years, with a neuropsychologi-cal test battery assessing intellectual ability (WAIS-R), verbal memory,

visuomotor and executive functions. Patients were examined clinicallyand myoclonus severity was evaluated with ‘myoclonus with action’ -partfrom the Unified Myoclonus Rating Scale. On the basis of myoclonuswith action score the patients were classified into three disability groups:mild, moderate and severe. 46 healthy volunteers (19 M, 27 F), mean age32 years, were the controls for the neuropsychological evaluation.

Result: The patients with ULD had lower Verbal and Performance IQsthan the controls (p<0.001) and impaired performance in flexible visuo-motor task (p<0.001). The patients had poorer immediate verbal memory(p<0.01) but delayed memory (percentage of retained material) did notdiffer between the groups. Patients with mild and moderate disability hadimpaired executive functions (p<0.01). Most patients with severe disabil-ity could not accomplish executive function tests and this group wasexcluded from this analysis.

Conclusion: The ULD patients are impaired in several cognitivedomains, in visuomotor, executive and intellectual functions. Delayedmemory is normal and memory disorder is not characteristic to ULD.The study has been funded by the Academy of Finland, the NEUROResearch Programme and UCB Pharma.

031EVIDENCE FOR COGNITIVE DEFICITS INUNTREATED PATIENTS WITH NEWLY DIAGNOSEDEPILEPSYJ. Witt, and C. HelmstaedterUniversity Clinic of Bonn, Bonn, Germany

Purpose: The objective of our study was to assess cognition in newlydiagnosed and untreated patients with epilepsy in order to determine theprevalence and the determinants of cognitive deficits at this early stage ofthe disease.

Method: A total of 247 untreated patients with newly diagnosed epi-lepsy underwent a brief test battery focusing on attention and executivefunctions (EpiTrack�) and memory (short form of the VLMT). In addi-tion, the assessment included ratings of self-perceived deficits in atten-tion and memory.

Result: Impairments in attention and executive functions were seen in49.4% of the patients, memory deficits in 47.8%. Unimpaired perfor-mance in both domains was observed in 27.9% of the cases. Self-per-ceived deficits in attention were only reported by 28.7% of the patientsand memory impairments were complained by 25.1% of the patients. Alower education and a symptomatic, i.e. lesional cause of epilepsy wereassociated with worse performance in attention and executive functions,whereas worse memory performance was related to generalized tonic-clonic seizures.

Conclusion: Results indicate a high prevalence of cognitive deficits atan early stage of epilepsy which calls for consideration in the daily clini-cal care. Patients appear to underreport cognitive deficits. Thus, a routineapplication of a brief standardized neuropsychological screening beforethe initiation of a pharmacological treatment would be appreciated to pro-vide a baseline to evaluate subsequent treatment success, to eventuallyinitiate countermeasures, and to monitor the course of the disease.

032COGNITIVE FUNCTION IS IMPAIRED IN PATIENTSWITH IDIOPATHIC GENERALISED EPILEPSY ANDTHEIR UNAFFECTED FAMILY MEMBERSF. A. Chowdhury*, L. Nashef*, R. D. Elwes*, andM. P. Richardson�

*King's College Hospital, London, UK; and �King's CollegeLondon, London, UK

Purpose: The profile of neuropsychological impairments in patientswith idiopathic generalised epilepsy (IGE) includes a wide range of fron-

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tal lobe functions. Assessment of neuropsychological function is com-plex because of the interaction of the underlying aetiological process,consequences of seizures and anti-epileptic medications.

Method: Forty age-matched normal control subjects, 36 patients withIGE, and 38 unaffected first-degree relatives of patients were studiedusing a range of neuropsychological tests; trail-making test, matrix rea-soning, verbal fluency (letter and category), N-back working memorytask, Stroop response inhibition and Connors’ Continuous PerformanceTask (CPT). Verbal IQ was measured using National Adult Reading Test(NART). Statistical testing used Bonferroni correction of 8 for each neu-ropsychological test administered.

Result: Patients performed significantly worse than controls on NART(p=0.006), matrix reasoning (p<0.001), letter and category fluency(p<0.001) and CPT omissions (p<0.001). Relatives also performed sig-nificantly worse than controls on matrix reasoning (p=0.002) and CPTomissions (p=0.001), despite having no significant difference in verbalIQ (p=0.711) using NART. There were significant linear trends betweenthe three groups in matrix reasoning (p<0.001), letter and category flu-ency (p<0.001) and CPT omissions (p<0.001), with relatives falling part-way between controls and patients.

Conclusion: Reduced cognitive performance is found in unaffected rel-atives of patients with IGE as well as the patients themselves, suggestingthis is related to a familial risk of epilepsy rather than a consequence ofseizures or anti-epileptic treatment.

Surgical TreatmentTuesday, 02 October 2012

033SEIZURE OUTCOME TEN YEARS AFTER RESECTIVEEPILEPSY SURGERY - A POPULATION-BASED, PRO-SPECTIVE, LONGITUDINAL STUDYA. Edelvik*, B. Rydenhag*, R. Flink�, and K. Malmgren**Sahlgrenska Academy, University of Gothenburg, Gothenburg,Sweden; and �Uppsala Akademiska Hospital, Uppsala, Sweden

Purpose: The aim of this study was to investigate seizure outcome 10years after resective epilepsy surgery in a national population-basedcohort of adults and children.

Method: The Swedish National Epilepsy Surgery Register encompassesdata on all epilepsy surgery procedures in Sweden since 1990 and is com-pletely prospective since 1995. Data is collected before and at surgery,and after two, five, 10 and 15 years. In this study, we analysed seizureoutcome for all patients who had resective epilepsy surgery in Sweden1995–2000 and had undergone 10-year follow-up (N=287). Freedomfrom seizures with impairment of consciousness (ILAE class 1 and 2) isreported for the year before follow-up. The percentages/numbers ofpatients with sustained seizure freedom (ILAE class 1 and 2) are alsoreported.

Result: Of the 287 patients, 211 had undergone temporal lobe resections(TLR) and 76 extratemporal resections (XTLR). 10 years after TLR 62%(131/211) were seizure free compared to 59% after two years. 36% (77/211) had sustained seizure freedom at 10 years compared to 51% (107/211) after two years. 43% (33/76) were seizure free 10 years after XTLRcompared to 39% after two years. 26% (20/76) had sustained seizure free-dom at 10 years, compared to 37% at two-year follow-up.

Conclusion: In this prospective population-based study, the percentageof patients who were seizure free the year before follow-up was stable 10years after epilepsy surgery, compared to the two years’ follow-up. How-ever, the percentage of patients with sustained seizure freedom after sur-gery declined over time.

034RESECTIVE EPILEPSY SURGERY FOR MALFORMA-TIONS OF CORTICAL DEVELOPMENT IN INFANCYAND EARLY CHILDHOODT. Otsuki, A. Takahashi, T. Kaido, Y. Kaneko, R. Honda,K. Sugai, E. Nakagawa, and M. SasakiNational Center of Neurology and Psychiatry, Tokyo, Japan

Purpose: Frequent epileptic seizures in infants cause sever epilepticencephalopathy with a catastrophic nature associated with progressivedevelopmental delay. When epileptogenic pathology such as corticaldysplasia is identified, early surgical intervention is considered althoughrisk and prognosis of surgical intervention in infancy and early childhoodis not well known.

Method: We have operated 56 children with cortical dysplasias less than6 years old at surgery in our institute during 2000 to Aug 2011. The age atsurgery was from 2 to 71 months old (mean 1y11m) and the follow-upperiod was from 6 months to 10 years (mean 3y10m). All the patientsdemonstrated disabling daily seizures such as frequent spasms and tonicseizures. Comprehensive presurgical evaluation including EEG, MRI,video-EEG monitoring, PET, MEG and developmental evaluation wasindicated to all the children and ictal SPECT with SISCOM analysis wasindicated in 27 selected cases. Intracranial EEG monitoring was per-formed in 7 cases elder than 3 years old under sedation and intensive care.The location of the MRI lesion was frontal in 20, temporal in 5, parietalin 5, occipital in 2, multilobar in 6 and hemispheric in 18 cases (16hemimegalencephaly).

Result: Surgical procedure was 18 hemispherotomy (17 vertical, 1 hori-zontal), 7 multilobar, 15 lober and 16 focal resection. Seizure outcomewas Engel's class I in 39 cases (70%), class II in 2 (3%), class III in 6(11%) and class IV in 9 (16%). There was no statistical difference in sei-zure outcome between surgical procedures. Surgical complications were1 post-operative hydrocephalus, 1 chronic subdural hematoma and 1 tran-sient meningitis. No motality nor sever morbidity was experienced in ourseries.

Conclusion: Favorable surgical prognosis can be obtained by resectiveepilepsy surgery for children in infancy and early childhood when epilep-togenic pathology is demonstrated by MRI and/or functional brain imag-ing.

035EXTRATEMPORAL EPILEPSY SURGERY IN ELO-QUENT BRAIN REGIONS USING FUNCTIONAL NEU-RONAVIGATION AND INTRAOPERATIVE MRI(IOPMRI)K. Roessler, B. Sommer, P. Grummich, B. Kasper, I. Bl�mcke,H. M. Hamer, and M. BuchfelderUniversity Hospital Erlangen, Erlangen, Germany

Purpose: A retrospective study was performed to analyze the impact offunctional neuronavigation and intraoperative magnetic resonance imag-ing (iopMRI) during extratemporal epilepsy surgery on neurological andepilepsy outcome.

Method: From 2003–2011 twenty-five patients with a mean age of 36years (range: 12–67; 14 female, 11 male) were resected on focal epilepto-genic lesions close to speech/motor areas or adjacent to eloquent fibretracts. Preoperatively, motor-sensory and speech areas and fibre tractswere mapped using functional MRI and DTI imaging, respectively. Func-tional data were integrated into intraoperative neuronavigation and dis-played through the microscope during surgery. Histopathology was FCDin 5, gliosis in 6, dysembryoblastic neuroepithelial tumor in 2, cavernoushemangioma in 5, ganglioglioma WHO�I in 4 and glioma WHO�I–III in3 patients. The postoperative follow-up period was 37.2 (4–89) monthsmean.

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Result: According to iopMRI scans, 100% resection of epileptogeniclesions was achieved in all patients. In 4 of them, an intraoperative sec-ond look procedure according to iopMRI was necessary to completeresection. Transient dysphasia was seen in 2/14 patients, permanent dys-phasia found in 2/14 patients. Permanent quadrantanopia was observed in2/8 patients. Of patients with functional mapping of the motor cortex andpyramidal tract, 1/19 experienced a temporary monoparesis. Favourableseizure control (Engel classification I and II) was achieved in 80% of thepatients.

Conclusion: In our retrospective analysis, we demonstrated that resec-tion of epiletogenic lesions close to eloquent cortex and fibre tracts canbe performed safely and efficiently by integration of multimodal neuro-navigation and functional imaging during surgery.

036USEFULNESS OF POSITRON EMISSION TOMOGRA-PHY IN DECISION MAKING FOR EPILEPSY SURGERYC. Rathore*, J. Dickson�, P. Ell�, and J. Duncan�

*Sree Chitra Institute of Medical Sciences and Technology,Trivandrum, India; �University College London Hospitals,London, UK; and �National Hospital for Neurology andNeurosurgery, London, UK

Purpose: To investigate the utility of Flurodeoxy-glucose PositronEmission Tomography (FDG-PET) in decision making for epilepsy sur-gery

Method: All patients with nonlocalizing or discordant information onnon-invasive evaluation (clinical, electrophysiological and 3T-MRI)underwent FDG-PET at our centre. PET scans were reviewed by twoinvestigators blinded to clinical data. PET was considered useful if it ledto surgery directly, helped in planning intracranial EEG (icEEG) or madesurgery improbable. Final localization was based upon the discussion inmultidisciplinary meetings supported by icEEG and/or postoperative sei-zure freedom, when available.

Result: Ninety adult patients (median age, 34years) underwent FDG-PET; 76 had normal MRI and 14 had electrophysiological and MRI dis-cordance. Final localization was mesial temporal lobe epilepsy (MTLE,n=6), lateral TLE (n=22), frontal lobe epilepsy (n=32), and temporal-plusepilepsy or other extratemporal lobe epilepsies (15 each). FDG-PET scanwas normal in 46 patients. It led to surgery without intracranial EEG infour patients (right MTLE) and helped in planning icEEG in 31 patients.Seven patients had bilateral/diffuse hypometabolism making surgeryimprobable and FDG-PET gave false localizing information in twopatients. Nine Of 14 patients who underwent surgery to date became sei-zure free and three patients could not proceed to surgery after icEEG.Others are awaiting icEEG (16) or declined surgery. Only three patientswith normal PET scan proceeded to icEEG or surgery (p=0.001). FDGPET provided equivalent information in all epilepsy localizations.

Conclusion: In ~45% of presurgical patients with normal or discordantMRI, PET scan provided information that helped decision making.

Clinical NeurophysiologyTuesday, 02 October 2012

037EEG FINDINGS IN 261 SEQUENTIAL PATIENTS WITHALTERED MENTAL STATUS PRESENTING TO THEEMERGENCY DEPARTMENTA. C. Grant*, S. Abdul-Baki*, V. Arnedo*, G. Chari*,E. Koziorynska*, D. Maus*, T. Mcsween*, K. A. Mortati*,

A. Reznikov*, H. Valsamis�, R. Cracco*, S. Malhotra*,A. Omurtag�, A. Fenton*, and S. Zehtabchi�

*SUNY Downstate Medical Center, Brooklyn, NY, USA; �KingsCounty Hospital Center, Brooklyn, NY, USA; and �Bio-SignalGroup, Brooklyn, NY, USA

Purpose: To identify the prevalence of EEG abnormalities in patientswith altered mental status (AMS) presenting to the emergency depart-ment (ED). Up to 10% of patients evaluated in the ED present with AMS.The prevalence of EEG abnormalities in this population is not known.

Method: Prospective study at two urban EDs in Brooklyn, NY. Inclu-sion: patients over 13 years old with AMS. Exclusion: an easily correct-able cause of AMS (e.g. hypoglycemia, opioid overdose). A 30-minuteEEG was performed on each subject as soon as possible after presenta-tion, usually within 1 hour.

Result: 301 patients were screened and 261 enrolled over 10 months.Mean age was 58.9y (SD 19.9). 78% of EEGs were abnormal. EEG find-ings: slowing only - 142 (54.4%), normal - 51 (19.5%), interictal epilepti-form discharges + slowing - 32 (12.3%), triphasic waves - 9 (3.4%),burst-suppression - 8 (3.1%, iatrogenic in 7), status epilepticus (SE) - 7(2.7%), seizure - 4 (1.5%), epileptiform only - 3 (1.1%), uninterpretable -5 (1.9%). 41 (15.7%) studies were partially obscured but contained suffi-cient interpretable data for clinical categorization.

Conclusion: ED patients with AMS have a very high prevalence of EEGabnormalities, most often diffuse slowing. 4.2% revealed SE or isolatedseizure(s), but another 2.7% demonstrated burst-suppression due to acutetreatment of SE. Nearly 20% of EEGs were normal, which rules out SE,seizure and encephalopathy as causes of AMS. Fewer than 2% were com-pletely obscured by artifact. EEG in the ED can provide useful informa-tion to narrow the differential diagnosis of AMS patients.

Supported by 1RC3NS070658

038IS ECOG DURING EPILEPSY SURGERY FOR MESIALTEMPORAL SCLEROSIS OF ANY USE?J. Chan, N. Lawn, and J. DunneRoyal Perth Hospital, Perth, WA, Australia

Purpose: The use of electrocorticography (ECoG) in epilepsy surgeryvaries widely as do methods of anaesthesia, recording and interpretation.Its role in guiding epilepsy surgery is debated particularly in patients withmesial temporal sclerosis (MTS). Significant inter-centre disparities inoutcome are seen following MTS surgery, with some centres using ECoGreporting better outcomes. We sought to study the ECoG findings and sei-zure outcomes in patients undergoing epilepsy surgery for MTS.

Method: We studied 73 consecutive patients with refractory epilepsywho had surgery for MTS with a minimum of 1-year follow up (median8.9 years, range 1–18.8 years). All surgeries were performed under gen-eral anaesthetic, usually sevoflurane. Pre-resection ECoG was recordedwith two 4-contact subdural strips (inferior temporal and lateral tempo-ral). Antero-mesial temporal resection was performed and tailored basedon the initial and postresection ECoG. ECoG was analysed blinded topatient details and outcomes.

Result: Overall, 58 patients (79%) had an Engel class I outcome. Of 61patients (84%) with pre-resection spikes, those with an inferomesialrather than lateral maximal field had a better outcome (88% mesial vs.64% lateral Engel class I; p=0.04). Engel class I outcomes occurred in75% of 12 patients with no pre-resection spikes, 94% of 34 patients withpre-resection spikes and none after initial/additional resection, and 63%of 27 patients with residual spikes after initial/additional resection(p=0.01).

Conclusion: ECoG during surgery for MTS at our centre provides usefulinformation for guiding surgery and predicting prognosis.

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039IMPLEMENTATION OF HOME VIDEO-EEG-TELEME-TRY AT KING'S COLLEGE HOSPITAL (KCH), LON-DONF. Brunnhuber*, S. Goyal�, D. Amin�, Y. Nguyen�, andM. P. Richardson�

*King's College Hospital, London, UK; �London; and �King'sCollege London, London, UK

Purpose: Aim: We present KCH's experience of the first 50 home video-telemetry (HVT) patients.

Method: HVT met the MRC definition of a complex intervention, andwe used its guidance to evaluate the process of piloting, evaluating,developing and implementing this new clinical service.

Result: Our feasibility study (n=5) with a test re-test design found nodifference in the quality of recording or clinical yield between inpatientvideo-telemetry (IVT) and HVT. The pre-implementation study (n=8)showed an excellent patient satisfaction. We also discuss the findings ofthe main stakeholder survey (consultants and technicians). Our economicmodelling demonstrates a clear financial superiority of HVT over IVT.

Conclusion: Our findings show that diagnostic video-telemetry for sei-zure classification and poly-somnographies can be carried out safely atthe patients’ home and poses no security risks for staff and can be effec-tively integrated into the service offering of a tertiary care centre as a rou-tine home or community-based procedure. Community or home-basedMDTs (multidisciplinary team meetings) is an unexpected advantage ofHVT and has the potential for future development for patients with com-plex conditions. HVT was preferred by our patients over IVT and pro-vides a means of reaching out to some of the most vulnerable patientgroups (children, patients with learning difficulties or other mental healthproblems), who would not otherwise benefit from this investigation oronly under great difficulties. We hope to encourage other clinical neuro-physiology departments and epilepsy centres to take advantage of ourexperience and consider adopting and implementing HVT, with the aimof a nationwide coverage.

040THE EUROPEAN EEG DATABASE AS A NEW STAN-DARD FOR LONG-TERM EEG RECORDINGS IN EPI-LEPSY PATIENTSA. Schulze-Bonhage*, M. Levanquyen�, F. Sales�, M. Neufang*,A. Dourado§, and M. Ihle**University Hospital Freiburg, Freiburg, Germany; �Hpital dela Piti�-SalpÞtri�re, Paris, France; �Hospitais de Universidadede Coimbra, Coimbra, Portugal; and §Universidade deCoimbra, Coimbra, Portugal

Purpose: Access to high quality long-term EEG recordings of epilepsypatients has so far been limited for many research groups active in thefield of clinical neurophysiology and epileptology. We here report on anewly established European Database offering high-quality surface andintracranial EEG data for EEG and epilepsy research.

Method: Supported by the EU-project EPILEPSIAE (Evolving Plat-form for Improving Living Expectation of Patients Suffering from IctAlEvents, Grant 211713), the epilepsy centers at the University HospitalsFreiburg, Germany, Hopital Piti�-SalpÞtri�re in Paris, France, and theUniversity Hospital Coimbra, Portugal have designed a database contain-ing long-term intracranial and surface EEG recordings. Inclusion criteriewere long-term recordings with a minimum of 4 days duration containing5 clinically manifest seizures.

Result: The complete European EEG database comprises 275 long-termrecordings from epilepsy patients, 223 obtained by surface-EEG usingthe 10–20 recording system and 52 based on intracranial subdural or

depth recordings with up to 122 channels. The datasets provide EEG datafor an average recording time of 150 hours at sampling rates of 250–2500Hz. EEG recordings have undergone standardized annotation with detailson the timing, patterns and evolution of seizures. Data files are supple-mented by comprehensive clinical patient information, MR imaging dataand antiepileptic medication.

Conclusion: The EU project has resulted in the by far largest and mostcomprehensive database for human surface and intracranial EEG record-ings. Information on access to data from this database for research groupscan be obtained at www.epilepsy-database.eu.

Functional MRIWednesday, 03 October 2012

041IMAGING MEMORY IN TEMPORAL LOBE EPILEPSY:REORGANISATION OF MEMORY FUNCTION FOL-LOWING ANTERIOR TEMPORAL LOBE RESECTION –RESULTS OF A LONGITUDINAL FMRI STUDYS. Bonelli*, P. J. Thompson�, M. Yogarajah�, R. Powell�,R. Samson�, A. W. Mcevoy�, M. Symms�, M. Koepp�, andJ. Duncan�

*Medical University of Vienna, Vienna, Austria; �Institute ofNeurology, London, UK; and �National Hospital for Neurology& Neurosurgery, London, UK

Purpose: Anterior temporal lobe resection (ATLR) may impair memoryfunction, typically verbal memory following left and visual memory fol-lowing right ATLR. We investigated reorganisation of memory functionin patients with temporal lobe epilepsy (TLE) before and after left or rightATLR and the efficiency of postoperative memory networks.

Method: We studied 46 patients with unilateral medial TLE (26 left) ona 3T GE-MRI scanner. All subjects had neuropsychological testing andperformed an fMRI memory encoding paradigm for words, pictures andfaces preoperatively and again four months after ATLR.

Result: Event-related analysis revealed that left TLE patients hadgreater left activation in the posterior medial temporal lobe (MTL) forencoding words postoperatively than preoperatively. Relatively greaterpre- than postoperative activation for encoding words in the ipsilateralposterior MTL correlated with better verbal memory outcome after leftATLR. Four months after left ATLR greater postoperative than preopera-tive activation in the ipsilateral posterior MTL correlated with less goodpostoperative verbal memory performance. These postoperative effectswere not observed for visual memory after right ATLR.

Conclusion: We found effective preoperative reorganisation of verbalmemory function to the ipsilateral posterior MTL, suggesting that it is thecapacity of the posterior remnant of the ipsilateral hippocampus ratherthan the functional reserve of the contralateral hippocampus that isimportant for maintaining verbal memory function after ATLR; earlypostoperative reorganisation to ipsilateral posterior or contralateral MTLstructures is inefficient. We also conclude that visual memory function inright TLE is affected differently by right ATLR than verbal memory inleft TLE.

042LOCALIZATION OF THE ICTAL ONSET ZONE USINGINTERICTAL EEG-FMRI IN THE PRESURGICALEVALUATION OF CONSECUTIVE PATIENTS WITHREFRACTORY FOCAL EPILEPSYS. Tousseyn, P. Dupont, S. Sunaert, and W. Van PaesschenKU Leuven, University Hospitals Leuven, Leuven, Belgium

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Purpose: The aim of this study was to explore how Blood Oxygen LevelDependent (BOLD) responses to interictal epileptic spikes during EEG-correlated functional MRI (EEG-fMRI) relate to the ictal onset zone(IOZ).

Method: Twenty-one consecutive adults with refractory focal epilepsyand a well delineated IOZ after a full presurgical evaluation includingsubtraction ictal SPECT co-registered to MRI (SISCOM) were studied.We delineated the IOZ as the region of SISCOM hyperperfusion (Z>1.5)within the planned or effective resection zone. Positive and negativefMRI responses (p<0.001) to clinically concordant and visually markedspikes (after standard EEG artifact removal) were used for qualitativeassessment of overlap with the IOZ.

Result: We observed clinically concordant interictal spikes in 10 of 21patients during fMRI, which resulted in both activations and deactiva-tions in all 10 patients. The maximal activation was statistically more sig-nificant than the maximal deactivation in 8/10. The maximal significantactivation cluster overlapped the IOZ in 9/10, although the voxel of maxi-mal activation was found within the IOZ in only 3/9. The cluster of maxi-mal deactivation was concordant with the IOZ in 2/10, with the voxel ofmaximal deactivation inside the IOZ in 1/2.

Conclusion: EEG-fMRI in consecutive patients with refractory focalepilepsy undergoing presurgical evaluation recorded epileptic spikes inonly 48%. The maximal significant fMRI activation cluster overlappedthe ictal onset zone in 90% of patients with spikes during fMRI. How-ever, the voxel of maximal activation was localized inside the IOZ inonly one third.

This study is funded by a grant for Applied Biomedical Research(TBM) of the Institute of Innovation by Science and Technology Flanders(IWT) (080658).

043MAPPING THE IRRITATIVE ZONE USING SIMULTA-NEOUS INTRACRANIAL EEG-FMRI AND COMPARI-SON WITH POSTSURGICAL OUTCOMEU. J. Chaudhary*, D. W. Carmichael�, R. Rodionov*,S. Vulliemoz�, C. Scott§, A. W. Mcevoy§, C. Micallef§, B. Diehl§,M. C. Walker*, J. Duncan*, and L. Lemieux**UCL Institute of Neurology, London, UK; �UCL Institute ofChild Health, London, UK; �University Hospital of Geneva,Geneva, Switzerland; and §National Hospital for Neurology andNeurosurgery, London, UK

Purpose: To determine the clinical significance and distribution ofspike-related haemodynamic changes across the whole brain using simul-taneous intracranial electroencephalography and functional magneticresonance imaging (icEEG-fMRI), particularly as icEEG has limited spa-tial coverage.

Method: Five patients with frontal lobe epilepsy undergoing invasivepresurgical evaluation were scanned. One to two 10-minutes EPI-ses-sions (TE/TR 40/3000ms; slices/gap: 38x2.5mm/0.5mm) and T1 volumewere acquired on 1.5T scanner using head RF-coil with patient at rest. 64channels of icEEG were recorded during EPI and reviewed after remov-ing scanner-related-artefacts. Pre-processed images were analysed usingSPM8. Spikes were classified according to their morphology and spatio-temporal distribution on icEEG and represented as zero-duration events(different types were modelled in separate regressors) and convolvedwith the canonical HRF and derivatives. SPM[F] maps obtained for eachspike type and for all types combined were overlaid on co-registered T1-volume and compared with the irritative zone defined on icEEG.

Result: All patients had statistically significant spike-related hemody-namic changes. BOLD changes were seen within the irritative zone inthree patients; remote clusters were seen in all patients. BOLD clusterswere predominantly in the hemisphere containing the irritative zone inthree patients with ILAE class-I outcome post-surgically, and were dis-tributed bilaterally remote from the irritative zone in one patient with

ILAE-class-IV post-surgical outcome. One patient did not proceed to sur-gery.

Conclusion: Simultaneous icEEG-fMRI reveals BOLD changes in dis-tributed networks across the whole brain for very focal epileptic dis-charges. These data suggest that the test may have clinical utility forpredicting surgical outcome.

044PREOPERATIVE FMRI IN TEMPORAL LOBE EPI-LEPSY: ASSESSMENT OF LANGUAGE-RELATEDAREASF. Villani*, C. Rosazza*, F. Ghielmetti*, L. Minati*, F. Deleo*,A. R. Giovagnoli�, G. Didato*, P. Vitali�, A. Parente�,L. D’Incerti*, R. Spreafico§, and M. Bruzzone**IRCCS Foundation Besta Neurological Institute, Milan, Italy; �

Fondazione IRCCS Istituto Neurologico C. Besta, Milano, Italy;�Istituto Neurologico Mondino, Pavia, Italy; and §I.R.C.C.S.Foundation Neurological Institute, Milano, Italy

Purpose: Surgical removal of part of the temporal lobe (TL) for tempo-ral lobe epilepsy (TLE) may be complicated by language impairments.Functional MRI (fMRI) may predict postsurgical language outcome. Inour study we assessed the impact of TLE on the language network.

Method: Data collected from 67 TLE patients (40 LTLE, 27 RTLE)were retrospectively analyzed with 15 controls. The fMRI assessmentincluded response naming (RN), verb generation (VGEN) and fluency(FT) tasks. A whole-brain and a ROI-based analysis with lateralizationindices were performed. Language tests were administered.

Result: The overall activation was left-lateralized in patients and con-trols. The FT elicited weaker activation of the TL compared to the othertasks. TL was activated anteriorly by the RN task, posteriorly by theVGEN task.

LTLE patients showed a decreased left-lateralization compared tocontrols. In RTLE patients the RN and FT revealed a left-lateraliza-tion similar to controls, but VGEN produced posterior temporal acti-vations also on the right side with a less lateralized languageactivation pattern.

The language assessment showed that left and right TLE patients hadsignificantly lower scores than controls on the Boston naming test.

Conclusion: RN and VGEN were the most useful tasks to lateralize andlocalize language areas in the TL. LTLE patients showed reorganizationof language in the right TL, suggesting an adaptive recruitment of contra-lateral regions. The paradoxical recruitment of right posterior temporalareas in RTLE patients may be related to language processing, as alsoright temporal regions are involved in accessing lexical and semanticinformation.

Structural and Functional ImagingWednesday, 03 October 2012

045DECREASED FUNCTIONAL FRONTAL LOBE CON-NECTIVITY IS ASSOCIATED WITH COGNITIVEIMPAIRMENT IN PEDIATRIC FRONTAL LOBE EPI-LEPSYH. Braakman*, M. Vaessen*, J. Jansen*, M. Debeij-Van Hall�,P. Hofman*, J. Vles*, A. �ldenkamp*, and W. Backes**Maastricht University Medical Center, Maastricht, TheNetherlands; and �Epilepsy Center Kempenhaeghe, Heeze, TheNetherlands

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Purpose: Cognitive impairment is frequent in frontal lobe epilepsy(FLE), but its etiology is unknown. With functional MRI, we explore therelationship between brain activation, functional connectivity and cogni-tive functioning in a cohort of pediatric FLE patients and healthy con-trols.

Method: Thirty-four children aged 8 to 13 years with FLE of unknowncause and 41 healthy age-matched controls underwent neuropsychologi-cal assessment and structural and functional brain MRI. We investigatedto which extent brain regions activated in response to a working memorytask and assessed functional connectivity between distant brain regions.Data of patients were compared to controls and patients were grouped ascognitively impaired or unimpaired.

Result: Children with FLE showed a global decrease in functional brainconnectivity compared to healthy controls, while brain activation pat-terns remained relatively intact. Children with FLE complicated by cog-nitive impairment typically showed a decrease in frontal lobeconnectivity. This decreased frontal lobe connectivity comprised bothconnections within the frontal lobe, as well as connections from the fron-tal lobe to the parietal lobe, temporal lobe, cerebellum, and basal ganglia.

Conclusion: Decreased functional frontal lobe connectivity is associ-ated with cognitive impairment in pediatric FLE. The importance offunctional integrity within the frontal lobe network, as well as its connec-tions to distant areas provides new insights in the etiology of the broad-range cognitive impairments in children with FLE.

046STRUCTURAL CHANGES OF THE WHITE MATTER INPATIENTS WITH JUVENILE MYOCLONIC EPILEPSYC. Roth, M. Belke, K. Menzler, S. Krach, F. Paulus, A. Jansen,M. Blanke, W. Einhuser-Treyer, F. Bremmer, F. Rosenow, andS. KnakePhilipps University Marburg, Marburg, Germany

Purpose: Juvenile myoclonic epilepsy (JME) is a common type of gen-eralized epilepsy. Amongst others it is characterized by the absence ofstructural brain abnormalities using magnetic resonance imaging (MRI)in the clinical routine. Recent findings in MRI studies however suggestregional changes of the brain in patients with JME, albeit those findingsare partly inconsistent. There has been a spatial variability in the patho-logical findings even though a tendency towards changes in the frontalcortex can be remarked.

Method: 19 patients with JME and 19 healthy controls, matched by sex,age and education were had a 3 Tesla MRI scan including a diffusionMRI scan (DTI). Those DTI images were analysed using Tract-BasedSpatial Statistics (TBSS) and the fractional anisotropy (FA) as a measureof the integrity of the white matter was computed.

Result: We found a significant reduction in the FA within the corpuscallosum (CC) in patients with JME compared to healthy controls. Thechanges were mainly in the anterior region of the corpus callosum.

Conclusion: The recuced FA within the corpus callosum suggests animpaired structural connectivity concerning the frontal lobe. Similarfindings have been published by a british group last year, so this may beconsidered as a robust result. Our findings are further evidence that regio-nal changes of the brain might exist in generalized epilepsy as well andsupport the hypothesis of impaired frontal network in patients with JME.

047HIPPOCAMPAL SUBFIELD ANALYSIS IN MESIALTEMPORAL LOBE EPILEPSYM. Deppe*, B. Weber�, J. Schoene-Bake�, and S. S. Keller�

*University of Muenster, Muenster, Germany; �University ofBonn, Bonn, Germany; and �King's College London, London,UK

Purpose: To map hippocampal subfield degeneration in patients withmesial temporal lobe epilepsy (mTLE) and hippocampal sclerosis (HS)using conventional MRI.

Method: We studied 82 patients with unilateral mTLE and HS (51 left,31 right) in context of pre-surgical evaluation and 81 healthy controls.MRIs were acquired using standard MPRAGE sequences at 3 Tesla. Vol-umes of hippocampal regions CA1, CA2-3, CA4 and dentate gyrus, su-biculum, presubiculum, fimbria, and hippocampal fissure were estimatedusing a recently developed method designed for automated analysis onconventional MRI (Van Leemput et al., 2009, Hippocampus 19:549).

Result: Atrophy of all hippocampal subregions ipsilateral to HS otherthan the hippocampal fissure was observed (p=0.001). Global hippocam-pal volume was asymmetrically bilaterally atrophic in patients, as wasfimbria volume in patients with left mTLE (p=0.01). The only clinical-anatomical correlation that existed was between duration of mTLE andvolume of the ipsilateral fimbria (p=0.02). However, this effect did notsurvive the necessary correction for age, given that age and ipsilateralfimbria were also significantly related (p=0.03).

Conclusion: These results are consistent with histological work indicat-ing that diffuse/total HS is common in patients with mTLE, and that pres-ervation of CA2 is seen in only a relatively small proportion of patients(Blumcke et al., 2007, Acta Neuropathol 113:235). The automatedmethod of hippocampal subfield quantification used here is adaptable topathological hippocampal structure, as illustrated in our patients withunilateral HS, and is therefore recommended for large-scale studies inneurological contexts.

048ALTERED INTERACTIONS WITHIN NEURAL NET-WORK SUPPORTING VERBAL WORKING MEMORYDUE TO HIPPOCAMPAL SCLEROSISP. Campo*, M. I. Garrido�, R. J. Moran�, I. Garc�a-Morales�,A. Gil-Nagel§, R. J. Dolan�, and K. J. Friston�

*Universidad Autonoma de Madrid, Madrid, Spain; �WellcomeTrust Centre for Neuroimaging, London, UK; �UniversityHospital of San Carlos, Madrid, Spain; and §Hospital RuberInternational, Madrid, Spain

Purpose: To evaluate local and remote changes in effective connectivityamong the regions of the neural network underlying encoding processesin patients with mesial temporal lobe epilepsy (mTLE) associated withunilateral hippocampal sclerosis (HS).

Method: We compared dynamic causal models, extracted from magne-toencephalographic recordings during verbal WM encoding, in mTLEpatients (n = 20) and controls (n = 12).

Result: Bayesian model comparison indicated that the best modelincluded bilateral, forward and backward connections, linking inferiortemporal cortex (ITC), inferior frontal regions (IFC) and medial temporallobe (MTL). Differences in model coefficients revealed that patientswere characterized by a decreased ipsilesional MTL-ITC connectivity,and an increased bidirectional IFG-MTL connectivity in the contralesion-al hemisphere (all p < 0.05). The influence from right IFC to right MTLwas inversely related to task performance (R2 = -.62, p < 0.05). A nega-tive correlation was also found between the connectivity strength of ip-silesional MTL-ITC and that of the contralesional MTL-IFG interaction(R2 = -.44, p = 0.05).

Conclusion: Left HS led to a dynamic adjustment/reorganization of theremaining network supporting verbal WM, affecting connections consid-ered to be of great functional relevance for WM performance. Thisaltered connectivity pattern may reflect compensatory, with varyingdegrees of efficacy, and pathophysiological mechanisms underlying ver-bal encoding deficits in left mTLE patients. Current results confirm thoseof a previous study and reinforce the hypothesis that a distributed neuralnetwork is affected as a result of localized brain damage.

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Acknowledgments: PC was supported by Spanish Ministry of Scienceand Innovation (Grant # RYC-2010-05748).

Paediatric EpilepsyWednesday, 03 October 2012

049PAROXYSMAL NON-EPILEPTIC EVENTS IN INFANTSAND TODDLERS: A SEMIOLOGY STUDYL. Chen*, E. P. Knight�, A. Shahid�, and I. Tuxhorn�

*1st Affiliated Hospital of Guangzhou Medical College,Guangzhou, China; and �Rainbow Babies and ChildrensHospital, Ohio, USA

Purpose: Paroxysmal non-epileptic events are frequently encounteredin pediatric population. We report our experience with PNEEs in a groupof infants and toddlers and analysis the clinical characteristic of theevents.

Method: Retrospectively reviewed all video EEG (VEEG) studies per-formed from January 2010 to April 2011. We included in the study con-secutive patients 2 years old or younger who had PNEEs recorded.Semiological analysis included: type of event, time of occurrence, clearonset and end, etc.

Result: Out of 81 patients 31 (38.3%) had non-epileptic events, 12 girlsand 19 boys (P>0.05). Three had both epileptic and non-epileptic seizuresand 28 had only non-epileptic events. Six had abnormal interictal EEG.Eight had family history of epilepsy (25.8%). Ten were developmentaldelay, and eleven had neurological abnormalities. Events occurred duringwakefulness in 16 (51.6%, P<0.05); during sleep in 7 (22.6%); in bothawake and sleep in 7 (22.6%). On semiology, 20 had behavioral features(64.5%), 10 with arrest of activity, 8 with staring, 6 with crying and 5with vocalization. 23 had motor features (74.2%) and 9 had autonomicfeatures (29.0%). Events classification: 8 staring spell (25.8%), 7 normalinfantile behavior (22.6%), 7 sleep myoclonus (22.6%), 4 shudderingattacks (12.9%), 4 infantile masturbation (12.9%), one tic, onechoreo-athetosis, one hyperekplexia, one gastro-esophageal reflux and one epi-sode of discomfort.

Conclusion: Paroxysmal non-epileptic events are very common ininfants and toddlers. Males were more than female in the study group.Non-epileptic staring spell is the most common PNEEs seen in this agegroup.

050EPILEPSY12 - UNITED KINGDOM COLLABORATIVECLINICAL AUDIT OF HEALTH CARE FOR CHILDRENAND YOUNG PEOPLE WITH SUSPECTED EPILEPTICSEIZURESC. Dunkley*, B. Waldron�, R. Maini�, F. Williams�, A. Brown§,R. Ranmal–, D. Flower**, F. Colaco��, K. Bowyer§, L. Notghi��,K. Martin§, R. Chin§§, H. Basu––, J. Paton***, M. Kirkpatrick��,C. Ferrie��, and W. P. Whitehouse§§§

*Sherwood Forest Hospitals, Sutton in Ashfield, UK; �LeicesterChildren's Hospital, Leicester, UK; �University of Dundee,Dundee, UK; §Nottingham University Hospitals NHS Trust,Nottingham, UK; –Royal College of Paediatrics and ChildHealth, London, UK; **Bristol Royal Hospital for Children,Bristol, UK; ��Scottish Children's Research Network, Dundee,UK; ��Birmingham Children's Hospital, Birmingham, UK;§§University of Edinburgh and Royal Hospital for Sick Children,Edinburgh, UK; ––Lancashire Teaching Hospitals NHS

Foundation Trust, Preston, UK; ***University of Glasgow andRoyal Hospital for Sick Children, Glasgow, Glasgow, UK; ��

Tayside Children's Hospital, Dundee, UK; ��Leeds GeneralInfirmary, Leeds, UK; and §§§University of Nottingham,Nottingham, UK

Purpose: To assess the quality of paediatric care for UK children, youngpeople and families affected by epilepsies and seizures.

Method: In 2009, the Royal College of Paediatrics and Child Health(RCPCH) ‘Epilepsy 12’ Audit began a pragmatic audit of UK paediatricepilepsy care against national guidelines. A project board representingUK stakeholders invited participation from all relevant local hospital andcommunity paediatric services. Audit domains were: 1. clinical servicedescription; 2. 12 clinical performance indicators and 3. a speciallydeveloped patient-related experience measure (PREM). The servicedescription was completed at the onset. Lists of children referred for elec-tro-encephalography helped identify eligible children aged 1 month to 16years who had received a first paediatric assessment for afebrile paroxys-mal episode(s) within a 6 month period from 2009. Retrospective datafrom case-notes review of the subsequent 12 months were entered onto aweb-based database. Children commenced on anti-epileptic medicationwere invited by letter to complete an anonymised PREM questionnaire.

Result: Data collection was completed in November 2011 and is cur-rently undergoing further analysis. All 197 audit units and 21 regionsenrolled. Participation rates were 98% (193/197) for clinical servicedescription, 94% (186/197) for clinical audit and 87% (172/197) forPREM domains. The clinical cohort consisted of 4991 patients, medianage 6.3 years, M:F 54:46%. 44% (2175/4991) of first paediatric assess-ments occurred within an acute presentation. 19% (974/4991) of childrenhad a documented neurodisability. Diagnosis of paroxysmal episode(s) atfirst assessment was recorded as: 46% (2298/4991) epileptic; 18% (897/4991) non-epileptic and 36% (1796/4991) uncertain. Diagnosis after 12months of care was recorded as: 6% (312/4991) single or ‘single cluster’epileptic seizure(s); 36% (1774/4991) 2 or more epileptic seizures; 44%(2198/4991) non-epileptic and 14% (707/4991) uncertain.

Conclusion: The paediatric epilepsy community, including acute andcommunity services and patient organisations, has contributed to thelargest description of the performance of paediatric epilepsy care in theUK to date. From the preliminary analysis, just over half the childrenwith paroxysmal episode(s) presented non-acutely with one third eventu-ally diagnosed as having recurrent epileptic seizures. Over the 12 monthsof follow-up, diagnosis varied and diagnostic uncertainty decreased.Final results will be placed in the public domain in September 2012.

051YOUNG ADULT ISCHEMIC STROKE-RELATEDACUTE SYMPTOMATIC AND LATE SEIZURES: RISKFACTORSR. Roivainen, E. Haapaniemi, J. Putaala, M. Kaste, andT. TatlisumakHelsinki University Central Hospital, Helsinki, Finland

Purpose: We assessed risk and baseline factors associated with acutesymptomatic seizure (ASS, occurring < 7 days), and late poststroke sei-zure (LPS, > 7 days) after ischemic stroke in young adults.

Method: We included all consecutive patients aged 15 to 49 with first-ever ischemic stroke (n=1008) between 1994 and 2007 treated at the Hel-sinki University Central Hospital, using Cox proportional hazard modelsto identify factors associated with seizures. Adjustment was for age, gen-der, vascular risk factors, admission hyperglycemia (> 6.1 mmol/L) andhyponatremia (< 137 mmol/L), use of psychiatric medication, strokeseverity (NIH Stroke Scale), and anatomic (Bamford criteria) and etio-logic (Trial of Org in Acute Stroke Treatment) stroke subtype.

Result: ASSs emerged in 35 (3.5%) patients. LPSs (n=102) occurred ata cumulative rate of 6.1% at 1 year to 11.5% at 10 years. In multivariate

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analysis, anxiolytic use at time of index stroke (hazard ratio 13.43, 95%confidence interval 3.91–46.14), moderate stroke severity (3.95, 1.86–8.41), cortical involvement (3.69, 1.66–8.18), and hyponatremia (3.26,1.41–7.57) were independently associated with ASSs. Risk factors forLPSs were total anterior circulation infarct (15.94 7.62–33.33), partialanterior circulation infarct (3.48, 1.52–7.93), history of ASS (3.94, 2.07–7.48), antidepressant use at the time of LPS (3.88, 2.46–6.11), hemor-rhagic infarct (1.94, 1.19–3.15), male gender (1.79, 1.10–2.92), andhyperglycemia (1.62, 1.05–2.51).

Conclusion: Despite the more heterogeneous etiologic background ofischemic stroke in young adults, major risk factors are similar to olderpatients. Risk factors for ASS and LPS differ and include factors that arenot directly related to stroke characteristics.

052KETOGENIC DIET AS AN EFFECTIVE ALTERNATIVETHERAPY IN CHILDHOOD REFRACTORY EPILEPSY:A SYSTEMATIC REVIEWA. K. Somale, and S. V. KondekarTopiwala National Medical College, Mumbai, India

Purpose: To systematically review recent studies on efficacy and safetyof ketogenic diet in pediatric refractory epilepsy.

Method: Literature reviewed using Medline searches and CochraneLibrary with the keywords epilepsy/therapy, refractory epilepsy, and thetext word ketogenic diet. Bibliographies of papers located by searchesand review articles were compiled. Papers published after year 2000,from various subcontinents worldwide, reporting use of ketogenic diet inchildren <18 years of age with medically refractory epilepsy of varied eti-ology like mitochondrial disorders, cortical dysplasia and symptomaticepilepsy were selected. The outcome measures used were the percentageof patients with complete elimination of seizures and >50% reduction inseizures, deaths and diet related adverse events.

Result: Nineteen studies met all criteria for inclusion. It included 6 ret-rospective, 6 prospective, 2 multicentric trials, 3 systematic reviews and2 randomized controlled trials.

The estimated proportion for obtaining complete seizure control bycombined analysis (confidence profile method) was 29.31% (95% confi-dence interval [CI]: 0.2631–0.3250) and was 41.81% (95% CI: 0.3838–0.4531) for greater than 50% reduction in seizures. Common adverseevents observed were gastrointestinal disturbances, infrequent lipidabnormalities and renal stones, however few deaths 1.29%(CI: 0.66–2.21) were reported while on the diet.

Conclusion: There is strong upcoming evidence in last decade to sup-port the safe and effective use of ketogenic diet in children with refrac-tory epilepsy.

Symptomatic EpilepsyWednesday, 03 October 2012

053VGKC ANTIBODIES IN EPILEPSY: DIAGNOSTICYIELD AND THERAPEUTIC IMPLICATIONSJ. LillekerGreater Manchester Neurosciences Centre, Salford, UK

Purpose: Voltage gated potassium channel (VGKC) antibodies aredirected against trans-synaptic and neuronal cell adhesion molecules.Recent studies have identified the presence of these antibodies in variouscohorts of patients with epilepsy, and have suggested a potential aetiolog-ical role for VGKC antibodies in epilepsy.

Method: We have undertaken systematic testing for VGKC antibodiesin patients with otherwise unexplained adult onset epilepsy, seen at a

regional neurosciences centre. Patients in whom VGKC antibodies wereidentified were given immunotherapy in addition to their antiepilepticdrug (AED) therapy. Clinical characteristics and response to immuno-therapy were analysed.

Result: Out of 128 patients tested, 4 had high titres of VGKC antibodies(>400 pM). Three are male, age range was 36 to 77 years. Seizure semiol-ogy was suggestive of temporal lobe onset in all patients. All patients hadon going seizures in spite of treatment with AED. One patient had CAS-PR2 antibodies, the other 3 were negative for both LGI1 and CASP2 anti-bodies. One patient had thymic enlargement. All patients were givenimmunotherapy with steroids and azathioprine, resulting in fall in VGKCtitres. In the patient with thymic enlargement VGKC titres fell followingthymectomy. All patients experienced improvement in seizure controlwith immunotherapy, and 3 have remained seizure free.

Conclusion: Identifying patients with VGKC antibodies associated withepilepsy has significant therapeutic implications, as immunotherapyappears to result in complete control of previously AED resistant sei-zures. The pathogenic antibody in patients presenting with epilepsymaybe directed towards an as yet unidentified component of the VGKCreceptor complex.

054EPILEPSY AND OTHER NEUROLOGICAL MANIFES-TATIONS ASSOCIATED WITH TUBEROUS SCLEROSISCOMPLEXP. Major*, F. Mathieu�, L. Ct�*, L. Crevier*, A. S. Kristof�, andJ. Landry�

*CHU Sainte-Justine - Universit� de Montr�al, Montr�al,Canada; �University of Toronto, Toronto, Canada; and �McGillUniversity, Montr�al, Canada

Purpose: Tuberous sclerosis complex (TSC) is a frequent cause of struc-tural focal epilepsy. This study aims to describe the characteristics of epi-lepsy and associated neurological manifestations in a large population ofpatients with TSC.

Method: Retrospective analysis of all patients who were admitted to thehospital or evaluated in the emergency room at the CHU Sainte-Justine(Montr�al) with a diagnosis of definite TSC from January 1987 to July2011.

Result: In 98 patients with a definite diagnosis of TSC, 79 (80%) hadepilepsy. The average age at seizure onset was 0.8 years (range = 0 to 8 y;SD = 1.6 y). Intractable epilepsy was found in 28/79 (35%), including 2patients who became seizure free after surgery. Average age at last fol-low-up visit was 18 years (range = 0 to 43 y; SD 10). Developmentaldelay was diagnosed in 56 (57%) patients, including 47 (83%) with epi-lepsy and 22/56 (40%) with intractable epilepsy. Of 12 (12%) patientswith autistic spectrum disorder (ASD), 11 (92%), and 5/12 (42%) hadintractable epilepsy. By mutational analysis (25/98 patients), epilepsywas reported in 16/18 (89%) patients with mutations in TSC2, and in 2/4(50%) patients with mutations in TSC1. Of the patients with subependy-mal giant cell astrocytoma (SEGA) (10/98), 5 underwent surgery, and 3were treated with mTOR inhibitors.

Conclusion: In patients with TSC attending a tertiary center, epilepsy,developmental delay, and ASD were common. Epilepsy was usually firstobserved in the first year of life, and was intractable in one third ofpatients.

055TRAUMATIC BRAIN INJURY AND SUBSEQUENT RISKOF UNPROVOKED SEIZURES: A POPULATION-BASEDCASE-CONTROL STUDYB. Mahler, C. Adelçw, T. Andersson, A. Ahlbom, and T. TomsonKarolinska Institutet, Stockholm, Sweden

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Purpose: To study traumatic brain injury as risk factor for unprovokedepileptic seizures in a population based cohort with incident seizurecases.

Method: In this population based case-control study, cases were 1885patients with new onset unprovoked seizures included in the StockholmIncidence Registry of Epilepsy. Controls, in total 15080-matched for gen-der, year of diagnosis, and catchment area- were randomly selected fromthe register of the Stockholm County population. Exposure was definedas a hospital discharge diagnosis of a traumatic head injury preceding thedate of seizure onset. Odds ratios (ORs) were calculated to assess the riskof developing unprovoked seizures after hospital admission for variouscategories of head trauma defined by ICD codes from the Swedish Hospi-tal Discharge Registry.

Result: Odds ratio (OR) with 95% confidence interval (95%CI) forunprovoked epileptic seizures was 2.75 (2.19–3.45) after a dischargediagnosis of head trauma, 1.93 (1.46–2.55) after cerebral concussion and8.86 (5.55–14.15) after a more severe brain injury (contusion or traumaticintracranial hemorrhage). The risk of developing unprovoked seizureswas highest during the first year, OR 5.42 (2.61–11.27) after cerebralconcussion and 30.53 (10.12–92.09) after severe head injury. The riskdeclined gradually with time but still ten years after the trauma OR was1.88 (1.27–2.79) for concussion and 2.44 (0.67–8.88) for severe headinjury.

Conclusion: We provide quantitative data on the risk of developingunprovoked seizures over time after brain trauma of different severity.Although highest the first year, the risk remains increased ten years afterthe trauma.

056EPILEPSY IN PRIMARY CEREBRAL TUMOURS:INTERIM RESULTS OF THE PERNO STUDY (PROJECTOF EMILIA ROMAGNA REGION ON NEURO-ONCOL-OGY)R. MichelucciIRCCS of Neurological Sciences, Bellaria Hospital, Bologna,Italy

Purpose: The present study is aimed to define the clinical characteristicsand outcome of tumoral epilepsy.

Method: This study is a section of the PERNO project - a prospectiveregistry of Primary Brain Tumours (PBT) in Emilia-Romagna Regionspanning a three year period (2009–2011). All patients with epileptic sei-zures were included in the study and followed up on a regular basis. Sei-zure semiology, tumour location and histology, and response totreatments were analyzed. A consent form was obtained by each patientor responsible guardian.

Result: Out of 610 PBT cases collected over the first two years, 114(19%) had epileptic seizures. Sufficient data for analysis are availablefor 107 (67 male and 40 female) patients. Seventy one patients(66%) had malignant PBT, mainly involving the frontal (61%) ortemporal (36%) lobes. Seizures were the first symptom in 80 cases(75%) and led to the diagnosis on PBT in most cases. Seizure typeswere focal motor (27%), somato-sensitive (11%) or tonic-clonic(26%). High seizure frequency at the onset was observed in 21% ofcases and status epilepticus in 10%. Preliminary follow up data areavailable in 59 cases with malignant gliomas and show an initialdrug-resistance of the seizures, which are usually halted only by sur-gical treatment.

Conclusion: In this group of mainly malignant PBT the seizures appearlesion-dependant: they are the initial symptom of the tumour, herald itsrelapse and may be controlled only by surgery.

This project was funded by the Research Program Regione-Universit�2007–2009 Area 1a – Innovative Research.

Basic Science 2Wednesday, 03 October 2012

057MTOR INHIBITION MODULATES EPILEPTOGENESIS,SEIZURES AND DEPRESSIVE-LIKE BEHAVIOR IN AGENETIC MODEL OF ABSENCE SEIZURES AND MILDDEPRESSION COMORBIDITY: A ROLE FOR INFLAM-MATORY RESPONSESE. Russo*, R. Citraro*, A. Constanti�, and G. De Sarro**University of Catanzaro, Catanzaro, Italy; and �UCL School ofPharmacy, London, UK

Purpose: The mammalian target of rapamycin (mTOR), a kinase regu-lating in the brain several physiological functions, seems to be involvedin many CNS pathologies.1 Previous work in animal models of convul-sive epilepsies, have suggested that mTOR modulators have beneficialantiepileptogenic effects.

Method: We investigated the effect of some treatment schedules (early-chronic; sub-chronic; acute) with the mTOR inhibitor rapamycin, on thedevelopment of absence-seizures, seizure parameters and depressive-likebehavior in WAG/Rij rats, a genetic model of absence epilepsy, epilepto-genesis and mild-depression comorbidity. Furthermore, we studied theinteraction between rapamycin and lypopholysaccharide (LPS) adminis-tration, which is known to aggravate absence seizures through increasedinflammatory responses.3

Result: Rapamycin (early-chronic) exhibited antiepileptogenic proper-ties also in this animal model; this effect was accompanied by pro-depres-sant effects. Both acute and sub-chronic (7day) treatments also had anti-absence properties, but the sub-chronic treatment produced contrastinganti-depressant properties in WAG/Rij rats not seen in Wistar rats. Therapamycin/LPS co-administration studies showed that rapamycinblocked/prevented LPS-dependent increase in absence-seizures, suggest-ing an anti-inflammatory-like protective action.

Conclusion: Concluding, we demonstrated a novel rapamycin antiepi-leptogenic effect in a well-established absence epilepsy animal model;we suggest that this effect may be mediated by inhibition of inflamma-tory processes during epileptogenesis. The action of rapamycin and therole of mTOR on glial cell-mediated inflammation have never been stud-ied before in epilepsy models; our experiments suggest new insights intothis intriguing field which deserves to be further explored.

References:1 Garelick, Kennedy. Exp Gerontol. 2011 46:155.2 Russo et al. Molecular Neurobiology. 2012.3 Kov�cs et al. Brain Res Bull. 2011 85:410.

058DEVELOPMENTAL CHANGES IN THE NUMBER OFGABAERGIC NEURONS OF THE THALAMIC RETICU-LAR NUCLEUS IN ABSENSE EPILEPSY RATSF. Onat*, S. Cavdar�, H. Hacioglu*, S. Yyldyz*, and O. Kirazly**Marmara University Medical School, Istambul, Turkey; and �

Koc University, _Istanbul, Turkey

Purpose: Absence epilepsy models have shown that the production ofseizures is related to an excess of GABAergic neurotransmission in thethalamus. The major source of GABAergic fibers to thalamic nuclei arefrom thalamic reticular nucleus (TRN). GABAergic neurotransmissionin the thalamus and TRN plays a critical role in the generation and controlof spike-and-wave discharge (SWDs) in absence epilepsy.

This study aims to quantify the number of GABAergic neurons in theTRN developmentally (P10, P20, P30 and P60 days) of Wistar rat (n=5for each developmental group) and compare the results with Genetic

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Absence Epilepsy Rats from Strasbourg (GAERS; n=5 for each develop-mental group).

Method: The intermediate TRN was removed from each animal and theGABAergic neurons were labelled using light-microscopy GABA immu-nohistochemistry. The disector method was used for the quantificationand the data was statistically analysed.

Result: The number of GABA labelled neurons in the TRN of Wistaranimals showed reduction with increasing development (from P10 toP60), but was not statistically significant. However, the GAERS showedan increase in the number of GABA+iv neurons with increasing develop-ment between P10 and P60. The correlation of the number of GABA+ivneurons of each developmental group between Wistar and GAERS ani-mals showed statistically significant difference in P30 (p=0.045) and P60(p=0.011).

Conclusion: The increase in the GABA+iv neurons, with developmentin GAERS, is likely to be related to the generation of SWDs or it may rep-resent a compensatory response of the TRN to the thalamocortical cir-cuitry in the absence seizures.

059THE DISEASE-MODIFYING EFFECT OF CARISBA-MATE IN THE LITHIUM-PILOCARPINE MODEL OFTEMPORAL LOBE EPILEPSY TRANSLATES INTOPRESERVED COGNITIVE FUNCTIONSJ. Faure*, G. Akimana*, E. Marques*, J. Cassel*, andA. Nehlig�

*Universit� de Strasbourg-CNRS, Strasbourg, France; and �

INSERM, Faculty of Medicine, Strasbourg C�dex, France

Purpose: Temporal lobe epilepsy (TLE) is one of the most frequent anddisabling epilepsy forms. Since many patients are pharmacoresistant,new antiepileptic and antiepileptogenic drugs are needed. A recent studyfrom our laboratory using a new drug, carisbamate (CRS), in the rat lith-ium-pilocarpine (li-pilo) model of TLE reported that CRS was neuropro-tective and displayed disease-modifying effects in a subgroup of rats.These rats did not develop TLE but pharmacosensitive absence-like epi-lepsy (ALE). Here we studied the consequences of this neuroprotectionon cognitive skills of ALE compared to TLE rats.

Method: Lithium-pilocarpine or saline were administered to 55 adultrats. A 90 kg/mg dose of CRS or saline was given one hour after status ep-ilepticus (SE) onset, repeated eight hours later and during six more days.The rats were video-monitored for two months and then their behavioralabilities were investigated. Tests including actography, plus-maze,beam-walking, Morris water maze, radial arm maze, double-H maze, andfive-choice serial reaction time task were used.

Result: The appearance of ALE occurred together with widespread neu-roprotection in 8/25 CRS-treated rats. ALE rats that underwent li-pilo SEand CRS treatment did not present significant cognitive impairmentscompared to control rats. TLE rats, treated or not with CRS, performedsignificantly worse than control and ALE rats in all tests.

Conclusion: The rats treated with CRS that developed ALE displayednearly complete preservation of cognitive functions. Thus, treatment withthis new drug has powerful disease-modifying effects that translate intoboth neuroprotection and impressive preservation of cognitive abilities.

060SPROUTING MOSSY FIBRES INNERVATE EXCIT-ATORY GRANULE CELLS AND INHIBITORY INTER-NEURONS IN THE HIPPOCAMPUS OF PATIENTSWITH TEMPORAL LOBE EPILEPSYT. M. Freiman, K. Leicht, M. C. Mueller, J. Zentner, andC. A. HaasUniversity Medical Centre Freiburg, Freiburg, Germany

Purpose: Temporal lobe epilepsy is characterized by a sclerosis of thehippocampus (Ammon's horn sclerosis) with a specific loss of pyramidalcells in CA1 and mossy cells in the hilus. Excitatory granule cells sur-vive, but show a reorganization of their axonal connections. Their axons,the mossy fibres, loose their target cells due to mossy cell death andsprout backwards into the granule cell layer. It was suggested so far, thatthis leads to a recurrent, excitatory circuit. The aim of this study was toexamine the target cells of mossy fibre sprouting, and determine whethermossy fibres impinge only on granule cells or also on other neurons, inparticular inhibitory interneurons (basket cells).

Method: Mossy fibres were traced with neurobiotin. In addition doubleimmunohistochemistry against synaptoporin (mossy fibres) and parval-bumin (basket cells) was used. Synapses were examined with electronmicroscopy, labelled in addition with post-embedding gamma-aminobu-tyric-acid (GABA)-immunogold.

Result: In human epileptic hippocampi sprouted mossy fibres inner-vated not only excitatory granule cells but also inhibitory interneu-rons. In addition, we show that the inhibitory axonal plexus aroundgranule cells is preserved and that the number of inhibitory axonterminals exceeds the number of excitatory sprouted mossy fibre ter-minals on granule cells.

Conclusion: Sprouting of mossy fibres does not simply results in anexcitatory circuit of granule cells because recurrent mossy fibres alsoinnervate inhibitory interneurons. This might lead to increased inhibitionand synchronization of granule cells because the extensive inhibitoryaxonal plexus is preserved and shows an additional innervation throughsprouted mossy fibres.


p061CHARACTERISING SEIZURE EVOLUTION INPATIENTS WITH IDIOPATHIC GENERALIZED EPI-LEPSY USING A COMPUTATIONAL MODELJ. R. Terry*, A. Nevado-Holgado�, F. Marten�, andM. P. Richardson§

*University of Exeter, Exeter, UK; �University of Oxford,Oxford, UK; �University of Bristol, Bristol, UK; and §King'sCollege London, London, UK

Purpose: We propose that the dynamic evolution of EEG activity duringepileptic seizures may be characterised as a path through parameter spaceof a computational model, reflecting gradual changes in underlying phys-iological mechanisms.

Method: We use an evolutionary algorithm to estimate parameters of acomputational model, according to the best fit obtained between themodel output and specific features of the clinically recorded EEG wave-form. We then evaluate the evolution of these parameters across thespike-wave discharge, by subdividing the discharge into individualspike-wave cycles and estimating parameters for each individual cycle.

Result: We find that model parameters evolve consistently when differ-ent spike-wave discharges from an individual patient are considered. Wefurther find that these evolutions vary between patients.

Conclusion: Our study shows that variations in different underlyingmechanisms can give rise to macroscopic dynamics (such as thoserecorded using EEG) that appear indistinguishable using standardclinical analysis tools. Our findings suggest that the evolution ofmodel parameters is a useful tool for identifying subtle variations inEEG dynamics that may ultimately be useful for characterising epi-lepsy type and distinguishing between patients whom at present aregiven the same diagnosis.

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p062COMPUTER ASSISTED ANALYSIS OF ELECTRICALSTIMULATIONS DURING STEREO-EEG RECORDINGSOF PRE-SURGICAL EPILEPTIC PATIENTSD. F. Boido*, S. Francione�, V. Gnatkovsky*, and M. De Curtis**Istituto Neurologico C. Besta, Milan, Italy; and �OspedaleNiguarda C Granda, Milan, Italy

Purpose: Surgical intervention is a preferred choice for the treatment ofpatients suffering from drug-resistant focal epilepsy. Invasive studieswith intracerebral electrodes are routinely performed when the bound-aries of the epileptogenic zone (EZ) are not well defined. During this pro-cedure, low-frequency bipolar stimulation (3ms-3mA pulses at 1 Hz for30s) at each recording site is systematically performed to identify EZ andto functionally map the explored region. Nowadays the analysis of therecorded electrical responses to these stimulations is performed by expe-rienced physicians, prevalently by visual inspection with time-consum-ing protocols.

Method: We developed an original computer assisted algorithm to ana-lyze evoked responses based on Labview; mono or bipolar responses ofeach tested couple of contacts are averaged and reliability assessed. Aver-aged responses selected on the base of their amplitude/area and features(peak amplitude, delay and area) are computed and stored. 3D-plot of allthe idealized responses are made available for interactive inspection andquantitative measures.

Result: Evoked responses are divided into three reliable consecutivephases. By comparing these phases it is possible to appreciate physiologi-cal and pathological connectivity between EZ and surrounding tissue.

Conclusion: Our analysis suite proved to be useful to assist the evalua-tions of physicians in order to establish both the epileptic zone bordersand the functional connectivity of the explored region. Moreover it is avaluable instrument for testing basic research hypothesis.

p063PARTIAL EPILEPSY IN CHILDREN CAN BE PRE-DICTED WITH FUNCTIONAL NETWORK CHARAC-TERISTICSE. G. A. L. Van Diessen*, W. M. Otte*, K. P. J. Braun*,C. J. Stam�, and F. E. Jansen**UMCU, Utrecht, The Netherlands; and �VUmc, Amsterdam,The Netherlands

Purpose: In children referred with a possible diagnosis of partial epilep-sies interictal electroencephalogram (EEG) is routinely performed butappears to be normal in many cases. In addition, evaluation of EEGabnormalities may be subjective and not very sensitive. In this study, weaimed to develop a multivariable diagnostic prediction model based onEEG functional network characteristics.

Method: Routinely performed interictal EEG recordings of 35 childrendiagnosed with partial epilepsies, and of 35 children in whom the diagno-sis epilepsy was excluded (control group), were analyzed (11 girls and 24boys, mean age 10 € 3 years). Children with partial epilepsy were indi-vidually matched on gender and age with children from the control group.Neither patients nor controls had a developmental delay, a history of feb-rile seizures, generalized epilepsy or were on chronic anticonvulsivemedicine. Resting-state EEG epochs, free of abnormal slowing or epilep-tiform activity, were selected to construct functional networks of corre-lated activity. We calculated multiple network characteristics often usedin functional network epilepsy studies and included them as predictors ina diagnostic prediction model. We used the random forest classifier, arobust ensemble algorithm, as a model. The core of the random forestclassifier is the binary decision tree, a data type that stores elements hier-archically in nodes. One node represented a network characteristic and isfollowed by two ‘children nodes’. In the process of building a binary deci-sion tree, decision rules are formed (split values). If we follow a path

down this hierarchical tree the decision rules guide the path either to theleft or right child node. The exact split values, and which network charac-teristics are assigned to which nodes, is found by fitting a decision tree togiven training data with known outcome labels. Our model had the high-est accuracy if trees were based on random selected subsets of 5 networkcharacteristics (out of 18). Accuracy was defined as the proportion ofboth true positives and negatives. Eventually, the lowest tree nodes directto the binary outcome labels: ‘partial epilepsy’ or ‘control’. After buildingthe random forest diagnostic prediction model, we assessed the ability todifferentiate between children with and without partial epilepsy using theareas under the Receiver Operating Characteristic curve (AUC). Sincethe AUC is typically considered to be optimistic when testing the diag-nostic model on the same data, we used internal validation methods tocorrect for this.

Result: Based on epileptiform EEG activity only, the diagnosis of epi-lepsy was supported with a sensitivity and specificity of 0.77 and 0.91respectively. Power spectral density of EEG measures revealed no differ-ences between patients and the control group. Furthermore, none of theindividual network characteristics used in our prediction model, was sig-nificantly different between groups. In contrast, the prediction model hada sensitivity of 0.96 [95% confidence interval (CI): 0.78–1.00] and speci-ficity of 0.95 [95%CI: 0.76–1.00] in correctly differentiating patientsfrom controls. Best model performance was found for the broadband fre-quency, with an AUC of 0.74.

Conclusion: Diagnostic accuracy in children with partial epilepsy ishighly improved with a diagnostic prediction model combining func-tional network characteristics derived from multi-channel EEG record-ings. Early accurate diagnosis is particularly valuable in children toinform and guide parents, to prompt treatment decisions and to limit theperiod of uncertainty and unnecessary risks.

p064SPATIO-TEMPORAL MODELS TO PREDICT AND CON-TROL EPILEPTIC SEIZURE DYNAMICSG. Baier, M. Goodfellow, P. N. Taylor, Y. Wang, and D. J. GarryManchester Interdisciplinary Biocentre, Manchester, UK

Purpose: EEG/MEG and fMRI studies have revealed complex spatio-temporal patterns of brain activity during focal-onset and generalised epi-leptic seizures. The origins and mechanisms of these phenomena at themacroscopic scale are important for the elaboration of new ways of treat-ment in epilepsy. For example, predictions of the effect of stimulation ofthe epileptogenic network, (as in closed loop seizure terminationdevices), require knowledge about how neuroanatomical location corre-lates with widespread abnormal activity. Here we demonstrate the use ofcomputational modelling of spatio-temporal epileptic patterns to inter-pret clinical recordings of epileptic seizures.

Method: Mathematical multicompartment models of large regions ofbrain tissue on the macroscopic scale are introduced to explain spatiotem-poral features of distinct seizure types in terms of interacting excitatoryand inhibitory neural populations. The model connectivity is based onconnectivity data from diffusion-tensor imaging in humans. Bifurcationstudies from nonlinear dynamics, and quantitative interrelation measuresfrom multivariate data analysis are applied for model validation andparameter estimation. Model output is compared quantitatively to clinicalEEG recordings.

Result: Large-scale multi-compartment models can recreate generic fea-tures of epileptic EEG in humans. Specifically, the distribution of spatialheterogeneities and heterogeneities in the connectivity lead to robustpatient-specific epileptic patterns while allowing for large inter-patient var-iability. Knowledge of the distribution of heterogeneities (e.g. in the cortex)allows to optimise stimulation protocols to suppress seizure activity.

Conclusion: Spatiotemporal computational models of the macroscopicneuropathophysiology in humans are a novel tool to describe epilepticseizure dynamics and provide a rationale to design patient-specific pre-dictions protocols for stimulation therapy.

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p065GLUTATHIONE TRANSFERASE POLYMORPHISMS INPATIENTS WITH PROGRESSIVE MYOCLONIC EPI-LEPSYM. Ercegovac*, V. Coric�, T. Simic�, N. J. Jovic�, D. V. Sokic§,J. Jakovljevic�, M. Kecmanovic–, D. M. Nikolic**,S. M. Jankovic*, A. Savic-Radojevic�, and M. Pljesa-Ercegovac�

*Clinic of Neurology, Clinical Center of Serbia, Belgrade,Serbia; �Institute of Medical and Clinical Biochemistry, Facultyof Medicine, University of Belgrade, Serbia, Belgrade, Serbia;�Clinic of Neurology and Psychiatry for Children and Youth,Belgrade, Serbia; §Clinic of Neurology Clinical Center ofSerbia, University of Belgrade, School of Medicine, Belgrade,Serbia; –University of Biology, Belgrade, Serbia; and**Belgrade University Medical School, Belgrade, Serbia

Purpose: It has been reported that increased generation of free radicalsor reduced activity of antioxidative defense mechanisms can cause sometypes of epilepsy and in addition, increases the risk of seizure recurrence.Glutathione transferases (GST) are superfamily of enzymes involved indetoxification and protection from oxidative damage. We hypothesizedthat genetic polymorphism of GSTM1, GSTT1, GSTA1, GSTO1andGSTP1may be associated with progressive myoclonus epilepsies (PME).

Method: Genomic DNA was isolated from 26 patients with PME (Un-verricht-Lundborg disease, Lafora body disease, Myoclonic Epilepsywith Ragged Red Fibers, ceroidlipofuscinosis) and 68 controls, matchedfor sex and age. The GSTA1, GSTO1 and GSTP1 genotypes were identi-fied by PCR-restriction fragment length polymorphism method (RFLP).GSTM1 and GSTT1 genotypes were determined by multiplex PCR.

Result: The frequency of GSTA1 low activity genotype TT was lowerin patients with PME (3.8%) compared to controls (11.8%) (OR=0.27,p>0.05). Distribution of GSTM1 genotype did not significantly differbetween cases and controls. Namely, GSTM1-null genotype was foundin 51.5% controls and 53.8% cases (OR=1.10, p>0.05). RegardingGSTO1, low activity genotype AA was lower in patients with PME(3.8%) compared to controls (8.8%) (OR=0.5, p>0.05). The frequency ofGSTP1 low activity genotype AG was lower in patients with PME(34.6%) compared to controls (44.1%) (OR=0.69, p>0.05). GSTT1-nullgenotype was found in 61.5% of patients with PME, which significantlydiffered from controls in which it was present in 25% (OR=4.80,p=0.001).

Conclusion: It can be concluded that presence of GSTT1-null genotypeincreases the risk for progressive myoclonic epilepsy.

p066DOPAMINE RECEPTORS IN NEOCORTEX OFPATIENTS WITH TEMPORAL LOBE EPILEPSY: COR-RELATIONS WITH MEMORY DISTURBANCESM. P. Mata Mendoza*, J. M. Cisneros-Franco�, A. R. Mart�nez�,M. A. Alonso Vanegas�, and L. L. Rocha**Center for Research and Advanced Studies, Distrito Federal,Mexico; and �Instituto Nacional de Neurolog�a y Neurocirug�a,Distrito Federal, Mexico

Purpose: To correlate abnormalities in binding to D1 and D2 receptorsas well as dopamine transporter in temporal cortex with memory distur-bances of surgically treated patients with pharmacoresistant temporallobe epilepsy (TLE).

Method: By autoradiography experiments, D1 and D2 receptors anddopamine transporter binding was evaluated in temporal neocortexobtained from autopsies (n=8) and patients with TLE associated withmesial sclerosis (MTLE, n=12) and with TLE secondary to tumor orvascular lesion (n=11). The values obtained were correlated with neuro-

psychological evaluation (Rey Auditory Verbal Learning Test, The Rey-Osterrieth Complex Figure Test and Wechsler Memory Scale) focused todetermine memory affection. We divided them into two groups: epilepsywith memory affection and epilepsy without memory affection andresults were compared with those found in experiments using autopsymaterial.

Result: Memory affection was found in 10 patients with MTLE (83%)and in 2 patients with TLE secondary to vascular lesion or tumor(18%). These patients demonstrated disturbances in short and/or long-term memory, including visual and/or verbal memory. Patients withmemory disturbances demonstrated higher D1 receptors binding values(38%, p>0.05) in all cortical layers, when compared with patients with-out memory affection. No further comparisons were significantly dif-ferent.

Conclusion: Previous studies show that too much or too little stimula-tion of D1 receptors leads to working memory deficits. The presentstudy indicates that patients with TLE showing high D1 receptor pres-ent a deleterious effect on memory. This effect may be associated withexcessive D1 receptor stimulation. Study supported by CONACyT(project 98386).

p067RARE CLINICAL FEATURE OF EPILEPSY, REPORTOF TWO CASESM. NadeemNishtar Medical College, Multan, Pakistan

Purpose: How Epilepsy causes abnormal behaviours that is false agres-sive.

Method: Two patients 23 year and 27 year old with epilepsy wereobserved for three years, presented with false (pretended) agressivebehaviour. When ever they want to flippant with other people, they fightand beat them. The intensity of fighting is low than original intensity. soin daily life activities, epilepsy patient present with false agressive behav-iour. It is their way to flippant with others. The patients suffering fromepilepsy have manifested a false aggressive behavior. This has beenobserved that such patients during showing aggressive behavior, do notwant to give physical damage.

Result: Although epilepsy causes abnormal behaviours, but abnormalfalse agressive behaviour is also caused by epilepsy.

Conclusion: Abnormal false agressive behaviour is also caused by epi-lepsy.

p068UP-REGULATION OF METHYL CPG BINDING PRO-TEIN-2 IN INTRACTABLE TEMPORAL LOBE EPI-LEPSY PATIENTS AND EXPERIMENT ANIMALSY. Chen, S. Tao, and J. LiChongqing, China

Purpose: Methyl CpG binding protein-2 (MeCP2) is a multifunctionalnuclear protein. MeCP2 plays an important role in regulating dendriticmorphology, mediating synaptic transmission, spontaneous neurotrans-mission and short-term synaptic plasticity in the central nervous system(CNS). Our aim was investigate the expression of MeCP2 mRNA andprotein in intractable temporal lobe epilepsy patients and experiment ani-mals.

Method: Using reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry and double label immunofluorescence, wedetected MeCP2 expression in 35 temporal neocortex tissue samplesfrom patients with intractable temporal lobe epilepsy (TLE) and 14 histo-logical normal temporal lobe tissue samples from the control group. Wealso examined the timing of MeCP2 expression in the hippocampus and

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adjacent cortex of rats with temporal lobe epilepsy (lithium chloride-pilo-carpine model) at 1, 2, 7, 14, 30, and 60 days after kindling and the con-trol group.

Result: MeCP2 is expressed mainly in the nucleus of neurons, notexpressed in astrocyte. MeCP2 expression was significantly higher in theTLE group and experiment animals group as compared with the controlgroup. The expression of MeCP2 in the rat hippocampus and adjacentcortex after seizures gradually increased during the acute period (1, 2days) and the latent period (7.14 days) but decreased during the chronicperiod (30.60 days).

Conclusion: The up-regulation of MeCP2 in intractable TLE patientsand experiment animals suggest that MeCP2 may involved in the patho-genesis of TLE.

p069NETWORK TOPOLOGY AND SEIZURE INITIATION INIDIOPATHIC GENERALISED EPILEPSYM. P. Richardson*, F. A. Chowdhury*, T. Fitzgerald�,O. Benjamin�, R. D. Elwes§, L. Nashef§, and J. R. Terry–

*King's College London, London, UK; �University CollegeLondon, London, UK; �Bristol University, Bristol, UK; §King'sCollege Hospital, London, UK; and –University of Exeter,Exeter, UK

Purpose: We examined whether brain network topology in normal inte-rictal EEG differed between patients with IGE and normal controls. Wethen examined a dynamic model of seizure initiation based on these net-works, attempting to relate altered network structure in IGE with agreater liability to generate seizures.

Method: We studied 35 patients and 40 normal controls, using EEG (21scalp electrodes, sampling 256Hz, filtered 0.3–70Hz). Phase synchronybetween EEG electrodes was assessed in 5 frequency bands using EEG-lab. Unweighted undirected graphs were constructed for each subject andband; nodal degree variance (D) and small world index (SWI) were cal-culated for each network and compared between groups. Using a phe-nomenological model of seizure initiation, we examined the exit time inthe presence of noise, which we equate with seizure frequency.

Result: Using nonparametric statistical tests and Bonferroni correctionfor multiple comparisons, we found that D was lower in controls than inpatients in the beta and gamma bands (beta: p=0.040; gamma: p=0.032).SWI was greater in controls than patients in the beta band (p=0.031). Wefound that network structure in patients correlates with shorter escapetimes relative to network structures from controls, especially in beta andgamma bands.

Conclusion: EEG networks of functional connectivity in beta andgamma bands differ significantly between IGE and normals. Networksbased on patient data generate seizures more readily than normal net-works in a dynamic model.


p070SIGNIFICANT INVOLVEMENT OF TOLL-LIKERECEPTOR 4 (TLR4) AND RECEPTOR FORADVANCED GLYCATION END PRODUCTS (RAGE) INEPILEPTOGENESIS IN AN EXPERIMENTAL MODELOF MESIAL TEMPORAL LOBE EPILEPSY (MTLE)V. Iori, M. Maroso, R. Vertemara, M. Carli, T. Ravizza, andA. Vezzani

Mario Negri Institute for Pharmacological Research, Milano,Italy

Purpose: We studied the role of TLR4 and RAGE in epileptogenesisusing a mouse model of mTLE. These receptors are activated by endoge-nous proinflammatory danger signals, such as High Mobility Group Box1 released in injured brain and previously shown to play a pivotal role inictogenesis (Maroso et al, Nature Med, 2010).

Method: C57BL/6 adult male wild-type mice (WT) were intrahippo-campally injected with kainate to induce status epilepticus (SE) and spon-taneous recurrent (drug-resistant) epileptic activity. Age and gender-matched C57BL/6 TLR4 and RAGE knock-out (KO) mice were similarlytreated. We compared mice for epilepsy development, cognitive perfor-mance, neuropathology and neurogenesis (doublecortin, DCX staining)

Result: SE duration and severity and the onset time to spontaneousepileptic activity were similar in all groups. However, the frequency ofepileptic events was significantly reduced by 60% and 30% in TLR4and RAGE KO, respectively, vs WT mice. Epileptic mice of eithergenotype and WT epileptic mice had similar memory impairment,comparable cell loss (except in CA1 where RAGE KO showedincreased neurodegeneration) and granule cell dispersion. DCX stain-ing was absent in epileptic WT and RAGE KO mice; notably, DCXpositive cells were present in epileptic TLR4 KO mice similarly to nonepileptic control mice.

Conclusion: Activation of RAGE and TLR4 signaling by endogenousdanger signals significantly contributes to the severity of epilepsy devel-oping after SE. These receptors differentially affect the fate of newly gen-erated neurons and CA1 cell survival in epileptic tissue. Our findingshighlight new molecular mechanisms involved in epileptogenesis.

p071ICTAL TACHYCARDIA PREVALENCE AND COMPARI-SON WITH OTHER FACTORS WHICH INFLUENCECARDIAC RATER. M. Mcguire, W. Liao, K. Eggleston, J. Begnaud, andM. T. BunkerCyberonics, Inc., Houston, TX, USA

Purpose: Literature suggests that heart rate changes may precede oroccur concurrently with some seizure types. Monitoring heart rate, there-fore, may be a useful diagnostic in seizure prediction or detection in somepatients with epilepsy.

Method: We analyzed simultaneously recorded EEG and ECG datafrom a large patient population during an epilepsy monitoring unit stay toassess the prevalence and frequency of ictal tachycardia. A seizure wasclassified as exhibiting ictal tachycardia if the heart rate reached at least100 bpm during the ictal period, and in comparison to the pre-ictal period,the heart rate increased by either 35 bpm or 55%. Additionally, we com-pared heart rate changes associated with seizures to those measured dur-ing moderate exercise.

Result: Annotated seizures with complete clinical diagnoses from sixty-four patients were analyzed. Thirty-four of these patients (53%) had atleast one seizure that met the definition of ictal tachycardia. Further, 50%of all seizures (84 of 167) within this subset of patients (n=34) exhibitedictal tachycardia. Compared with moderate exercise, seizures defined asictal tachycardia exhibited higher magnitude and more rapid changes incardiac rate.

Conclusion: The data indicate that ictal tachycardia is prevalent inpatients that primarily exhibit complex partial seizures originating inthe temporal lobe. The results suggest that heart rate changes associ-ated with seizures may be distinguishable from other factors whichaffect cardiac rate such as exercise. Therefore, monitoring heart ratemay serve as a viable diagnostic for indicating seizure onset or loggingseizure occurrence.

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p072CHARACTERIZATION OF MULTIPLE MITOCHON-DRIAL DNA DELETIONS IN SCLEROTIC HIPPOCAM-PUS OF PATIENTS WITH TEMPORAL LOBE EPILEPSYW. S. Kunz, G. Zsurka, and V. PeevaUniversity Bonn, Bonn, Germany

Purpose: In this work we addressed the molecular cause for the mito-chondrial dysfunction in hippocampal subfields of patients with hippo-campal sclerosis, one of the most common forms of therapy-resistanttemporal lobe epilepsy.

Method: Applying long-range PCR, single molecule PCR and a nextgeneration sequencing approach we identified, quantified and mappedmitochondrial DNA deletions in hippocampal subfields of patients withtemporal lobe epilepsy, who underwent epilepsy surgery. These mito-chondrial DNA rearrangements are an accepted cause for mitochondrialdysfunction in various neuromuscular disorders and aging.

Result: The deletion loads approached in the CA3 subfield and the den-tate gyrus of patients with hippocampal sclerosis 2–8% of total mitochon-drial DNA content. A major fraction of the detected deletions had the 3’breakpoint at a hot spot around np 16070 implying ROS-caused mito-chondrial DNA double strand breaks as potential mechanism of deletionformation. High levels of deleted mitochondrial DNA appear to correlatewith the presence of cytochrome c oxidase-negative and succinate dehy-drogenate-positive neurons in the CA3 and CA4 hippocampal subfields.Hippocampal samples from age-matched patients with epilepsy due tolesions in the temporal lobe did not contain elevated levels of deletedmitochondrial DNA.

Conclusion: Dysfunction of mitochondrial oxidative phosphorylation inthe epileptic focus of patients with Ammon's horn sclerosis appears to berelated to clonal expansion of specific types of deletions of mitochondrialDNA generated very likely by increased oxidative stress. This mecha-nism is proposed to be relevant for seizure generation in the sclerotic hip-pocampus of patients with temporal lobe epilepsy and Ammon's hornsclerosis.

p073DIFFERENTIAL MRNA EXPRESSION OF TUMORNECROSIS FACTOR AND KLOTHO IN TEMPORALLOBE EPILEPSY PATIENTS WITH HIPPOCAMPALSCLEROSISM. A. Teocchi, A. E. D. Ferreira, E. Oliveira, H. Tedeschi, andL. D’Souza-LiUniversity of Campinas, Campinas, Brazil

Purpose: Previous research in animal seizure models point to thepleiotropic cytokine TNFa as an important effector/mediator of neur-oinflammation and cell death. One of the primary events in seizureinduced cell death is the excessive release of glutamate with a conse-quent increase in intracellular calcium influx. Klotho (KL), originallyidentified as an antiaging protein, is emerging as an important calci-ophosphoregulatory hormone. Its cerebral function is unclear; how-ever, the klotho knockout mouse exhibits a phenotype resemblinghuman aging presenting neural degeneration and a reduction of syn-apses in the hippocampus. Moreover, it was demonstrated that TNFadown-regulates KL through NF-jB in animal models of chronic kid-ney disease and colitis. Our objective is to prove that a similar down-regulation occurs in temporal lobe epilepsy patients with hippocampalsclerosis (TLE+HS).

Method: We evaluated TNF, KL and NFKB1 relative mRNA expres-sion levels by Reverse Transcription quantitative PCR in resected hippo-campal tissue samples from 14 TLE+HS patients and compared them tofour post mortem controls. Two pairs of reference genes were used: GAP-DH and HPRT1 (classical) and ENO2 and TBP (alternative).

Result: Our results showed that TNF and NFKB1 were significantly up-regulated in TLE+HS patients (p=0.0035 and p<0.02, respectively) whileKL expression was significantly downregulated (p<0.02).

Conclusion: This is the first study relating KL with HS and epilepsy.Our data suggest that TNFa might affect KL expression in hippocampus.As a multifunctional protein, our finding on KL downregulation inTLE+HS patients opens several possible avenues of research that willhelp us to understand the complex pathophysiology in HS.

p074EPILEPSY AND SLEEP; A PERFECT MARRIAGE!!!I. J. Poddar, and K. M. HaridasKMC, Kolkata, India

Purpose: Older studies of patient-reported seizure precipitants have notevaluated whether different epilepsy syndromes are differentiallyaffected with pricipitating factors mainly sleep.

Method: Patients of a tertiary-care epilepsy center were consecutivelysurveyed with the use of a standardized questionnaire that lists precipit-ants that might trigger or exacerbate seizures . Patients were classifiedinto epilepsy syndromes according to International League Against Epi-lepsy criteria. Age and gender within groups defined by major precipit-ants were compared. Pearson's correlation was performed to evaluatecommon patterns of precipitants

Result: Of 500 patients, 58% cited at least one precipitant. In order offrequency, stress (22%), sleep deprivation (28%), sound and light flashes(26%), fever (08%), fatigue (03%) and others (13%). Stress, light andsound flashes, and sleep deprivation positively correlated. Rankings ofprecipitants varied within epilepsy syndromes, with patients with tempo-ral lobe epilepsy citing sleep infrequently compared with patients withother epilepsy syndromes. Menstrual effects were ranked highly withinmajor precipitants among women over age 14 and were especially notedby women with temporal lobe epilepsy (34%).

Conclusion: Many patients with epilepsy identify a precipitant that trig-gers or exacerbates seizures. The high correlation of stress, sleep depriva-tion, and fatigue suggests that they act through common mechanisms toworsen seizure control. Through identification of the effect of bothendogenous and exogenous precipitants among syndromes, moreresearch and counseling can be directed to specific precipitants.

p075NMDAR1 EXPRESSION IN THE TEMPORAL LOBEFROM INTRACTABLE EPILEPSY PATIENTSZ. Wang, W. Lin, and L. LuThe First Hospital of Jilin University, China

Purpose: In order to study NMDAR1 in the temporal lobe from intracta-ble epilepsy patients.

Method: Cortical temporal lobe brain were collected from 20 patientwith intractable epilepsy and 10 patients with traumatic brain injury . theNMDAR1 expression were detected by immunohistochemistry and wes-tern blot in both group.

Result: The results showed that expression of NMDAR1 in the experi-mental group was higher than the control group (p<0.001), the absor-bance value of NMDAR1 protein strip observed from intractableepilepsy patients was 0.4175€0.2321 compared to 0.2412€0.1458 in thecontrol group (p<0.005).

Conclusion: Expression of NMDAR1 in the temporal lobe from intrac-table epilepsy patients was higher than the control group

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p076ARE GLUTAMINE SINTHETASE EXPRESSION LEV-ELS ASSOCIATED WITH MESIAL TEMPORAL LOBEEPILEPSY WITH HIPPOCAMPAL SCLEROSIS?A. Martins Da Silva*, R. Branco�, B. Leal�, R. Rangel*,C. Carvalho�, A. Bettencourt�, J. Chaves*, A. Santos�,T. Magalh¼es�, M. Honavar§, M. Melo Pires*, B. Martins DaSilva�, and P. P. Costa�

*Hospital de Santo Ant�nio - Centro Hospitalar do Porto, Porto,Portugal; �Instituto CiÞncias Biom�dicas Abel Salazar, Porto,Portugal; �Instituto Medicina Legal - DelegaÅ¼o Porto, Porto,Portugal; and §Unidade Local de S�ude Matosinhos - PedroHispano, Matosinhos, Portugal

Purpose: Glutamate is an essential excitatory neurotransmitter involvedin diverse brain functions. Excess of extracellular glutamate can lead toexcitotoxicity and subsequent cell death. The glutamatergic system isregulated by glutamine synthetase (GS), an enzyme responsible for gluta-mate metabolism in astrocytes. Abnormalities in this pathway have beenimplicated in the onset and progression of several neurological diseasesincluding mesial temporal lobe epilepsy with hippocampal sclerosis(MTLE-HS). In this study, we evaluated the expression levels of GS inthe surgical removed lesions from hippocampal tissue and in the adjoin-ing temporal cortex of MTLE-HS patients.

Method: Twenty two patients with refractory MTLE-HS submitted tosurgery were studied. Surgical specimens of hippocampus (lesional andperi-lesional cortical area) were collected. These samples were comparedwith nine autopsy controls without Known neurological disorder. GSexpression levels were quantified by Real-Time PCR.

Result: The expression levels of GS were similar in the hippocampusand temporal cortex of MTLE-HS patients when compared to similardata from matched healthy controls.

Conclusion: Our results demonstrate that GS expression levels are notaltered in MTLE-HS. This absence of differences does not exclude thehypothesis of abnormalities in GS at protein and functional level. For thisreason, complementary studies are being performed to evaluate the pro-tein/activity of GS and to elucidate the role of glutamatergic system inthe aetiology of MTLE-HS.

Supported by a FCT grant PIC/IC/83297/2007

p077EXCITATORY AMINO ACID TRANSPORTER – 1EXPRESSION IN HUMAN MESIAL TEMPORAL LOBEEPILEPSY WITH HIPPOCAMPAL SCLEROSISB. Leal*, R. Branco*, R. Rangel�, A. Bettencourt*,C. Carvalho*, J. Chaves�, A. Santos�, T. Magalh¼es�,M. Honavar§, M. Melo Pires�, A. Martins Da Silva�,P. P. Costa*, and B. Martins Da Silva**Instituto CiÞncias Biom�dicas Abel Salazar, Porto, Portugal; �

Hospital de Santo Ant�nio - Centro Hospitalar do Porto, Porto,Portugal; �Instituto Medicina Legal - DelegaÅ¼o Porto, Porto,Portugal; and §Unidade Local de S�ude Matosinhos - PedroHispano, Matosinhos, Portugal

Purpose: Glutamate is the predominant excitatory neurotransmitter inthe Central Nervous System. Its excessive accumulation causes an ex-citotoxic process that can result in cell death. Glutamate transporters playan important role in regulating glutamate extracellular concentrations.EAAT1 (Excitatory Amino Acid Transporter 1) is a glutamate transporterhighly expressed in astrocytes. Dysfunction in EAAT1 has been impli-cated in the onset of several neurological disorders including epilepsy.However, controversy exists on whether EAATs expression is altered inpatients with Mesial Temporal Lobe Epilepsy with Hippocampal Sclero-sis (MTLE-HS). To clarify this controversy we evaluated the expression

levels of EAAT1 in the surgically removed lesions (hippocampus and theadjoining temporal cortex) of MTLE-HS patients.

Method: EAAT1 expression levels in the hippocampus (lesional andperi-lesional cortical area) were quantified by Real-Time PCR in 22MTLE-HS patients submitted to surgery and compared with 9 autopsycontrols with no history of neurological disorders.

Result: EAAT1 was overexpressed in both the hippocampus (p=0.008)and in the temporal cortex (p=0.018) of MTLE-HS patients when com-pared to autopsy controls.

Conclusion: Our results demonstrate that the glutamatergic pathway isaltered in the hippocampus of MTLE-HS patients. Additionally, EAAT1overexpression in adjoining cortex suggests that this area could beinvolved in disease progression. EAAT1 overexpression could beexplained by a compensatory mechanism to overcome the accumulationof glutamate in epileptic focus.

Supported by a FCT grant PIC/IC/83297/2007.

p078DEVELOPING A MULTI-MODAL DEVICE FOR NO-NEEG, EXTRAMURAL NOCTURNAL SEIZURE MONI-TORINGJ. Van AndelTeleEpilepsy Research Consortium; UMCU, Kempenhaeghe,SEIN, Utrecht, The Netherlands

Purpose: In epilepsy, 25% of patients have regular, intractable seizures,especially children with epilepsy syndromes and patients with gross brainabnormality and cognitive impairments. About half of seizures are atnight, posing problems in these vulnerable patient groups depending oncaregivers not sleeping in the same bed. A reliable seizure detection andalert system will provide a major step in patient safety, quality of life anddisease management, however presently this is lacking. A new multi-modal device using an optimized combination of nonEEG sensors isdeveloped. Based on preliminary studies 4 modalities were selected:audio, automated video frame analysis, ECG and 3D-accelerometry.

Method: A diagnostic study design is used to define optimal combina-tions of algorithms analyzing the 4 modalities in the target population:children <18, and mentally impaired adolescents and adults with majornocturnal seizures. The multimodal device is tested in an in-hospital set-ting in 100 patients, simultaneously with the gold standard of clinicalvideo-EEG. Modern methods of classification and regression analysisare applied to define optimal sets of joint thresholds for the modalities.The aim is to achieve a high detection rate for seizures, with a minimumof false alarms in seizure free periods. Patient factors are taken intoaccount, potentially allowing for tuning thresholds to individual patients.

Result: To demonstrate our method, an interim-analysis of results willbe presented in September 2012.

Conclusion: In this study, the validity of a newly developed device forhome detection of epileptic seizures during sleep in patients with majornocturnal seizures is tested.


p079THE RISK OF SEIZURES IN PROGRESSIVE MULTIPLESCLEROSISO. W. Howell*, R. Nicholas�, D. Gveric�, M. I. Rees*,F. Roncaroli�, and R. Reynolds�

*Swansea University, Swansea, UK; and �Imperial CollegeLondon, London, UK

24

Abstracts


Purpose: Cortical pathology is thought to contribute to motor, sensoryand cognitive difficulties experienced by people with multiple sclerosis(MS). The extent of cortical and deep grey demyelination is often greaterthan that of the white matter, and it has been shown that inflammation ofthe grey matter and subcortical areas is associated with an increased riskof epilepsy. We hypothesise that inflammation, demyelination and neuro-axonal damage, cardinal features of long-standing progressive MS, willlikely contribute to an increased risk of seizures.

Method: We compared clinical disease milestones and pathology withseizure status from a cohort of 115 cases of secondary progressive MS(73 female, disease duration: 26.5€10.8yrs; age died: 57.4€13.1yrs).

Result: Twenty two (19%) cases had at least a single seizure event, andthese cases differed to the MS group without seizures with respect to: ayounger age at progression (37.8€9.1 vs 42.6€10.2yrs, p=0.045), youn-ger age at wheelchair (41.4€10.3 vs 46.5€12.6yrs, p=0.035), younger ageat death (51.5€11.6 vs 58.8€13.2yrs, p=0.018) and shorter duration of theprogressive phase (12.7€6.3 vs 16.1€6.8yrs, p=0.05), but not total diseaseduration (p=0.127). Seizures risk was independent of gender or overlyingmeningeal inflammation (p>0.3). A more severe clinical diseasereflected the increased severity of global neuropathology (mean rating6.8€1 vs 5.6€2.3, p=0.005) and reduced brain weight (1082€135g vs1173€134g, p=0.01) for the MS plus seizure cohort at post-mortem.

Conclusion: Our analysis suggests that seizure occurrence in MS isinfluenced by disease course and likely reflects the accumulation of mye-lin and neuroaxonal damage in the cortex.

p080‘‘HERCULES’’: DEVELOPING AN INTEGRATEDHEALTH CARE SCHEME, BASED ON BIOMEDICALGENETICS, ADVANCED BIOMEDICAL INFORMATICSAND COMPUTER VISION FOR EARLY DIAGNOSIS,MONITORING AND TREATMENT OF CHILDRENWITH NEUROLOGICAL DISORDERS IN GREECE.PILOT APPLICATION IN ABSENCE LIKE SEIZURESP. Vorgia*, M. Pediaditis�, V. Kritsotakis�, H. Dimitriou*,M. Tsiknakis�, S. Voutoufianakis§, V. Danilatou§,D. Kafetzopoulos�, and D. Fotiadis–

*Medical School, University of Crete, Heraklion Crete, Greece;�FORTH, Heraklion Crete, Greece; �FORTH, Heraklion,Greece; §Venizelion General Hospital, Heraklion Crete, Greece;and –University of Ioannina, Ioannina, Greece

Purpose: Epilepsy is one of the most common chronic neurological dis-orders. Children and adolescents with active epilepsy in Europe are esti-mated at 0.9 million, meaning that 1% of the population of children isaffected. A significant proportion of them, reaching 30%, are pharmaco-resistant. Resistance to treatment has a heavy burden on children's qualityof life. The Hercules project aims to the development of an integratedhealthcare and research scheme specified for Childhood NeurologicalDisorders, and mainly for epilepsy.

Method: The main idea is to integrate medical, behavioral (motion-related) and genetic information in order to build innovative tools andnetworks for providing state-of-the-art quality of care. This health careimprovement will be achieved through better disease classification,knowledge discovery and invention of decision support systems. Theoverall architecture of the Hercules project includes: (a) the developmentof a biobank, (b) the development of an electronic health record, (c) theacquisition and installation of a state-of-the art video- electroencephalo-gram monitoring system for the detection and quantification of epilepticseizures.

Result: Absence like seizures are the first ones to be studied.

Conclusion: The information related to the technological requirements,the architectural design, the functional specifications that render Hercu-

les’ electronic health record innovative (it is designed to be compatible tothe widely recognized HL7 Reference Information Model architecture),the ongoing work and results from the area of computer-based video anal-ysis for detecting and quantifying epileptic seizures, will be presented.

p081DNA METHYLATION PROFILING REVEALS DIFFER-ENTIAL METHYLATION PATTERNS CORRELATEDWITH GENE EXPRESSION IN HUMAN EPILEPSYL. Wang, and X. WangThe First Affiliated Hospital of Chongqing Meidical University,Chongqing, China

Purpose: Few studies have addressed whether abnormal DNA methyla-tion contributes to differential gene expression in epilepsy. This studyaimed to define differential DNA methylation patterns in drug-refractoryepilepsy patients and to investigate the role of DNA methylation in epile-ptogenesis.

Method: We evaluated DNA methyltransferase 1 (Dnmt1) and Dnmt3aexpression in brain tissues of epileptic patients and then performed DNAmethylation profiling in brain tissues from epileptic and control patients(n = 3 of each) via methylated-cytosine DNA immunoprecipitationmicroarray chip. Differentially methylated loci were validated by bisul-fite sequencing-PCR, and the mRNA levels of candidate genes were eval-uated by reverse transcriptase PCR.

Result: We found that Dnmt1 and Dnmt3a was up-regulated in the braintissues of epileptic patients. We also found 224 genes that showed differ-ential DNA methylation between epileptic patients and controls. Thesegenes included those involved in the regulation of Rho, microtubule-based processes and mitogen-activated protein kinase scaffold activity.Among the seven candidate genes, three showed clear transcriptional reg-ulation by DNA methylation. TUBB2B and ATPGD1 exhibited rela-tively hypermethylated promoters and decreased mRNA levels, whereasHTR6 displayed a relatively hypomethylated promoter and highermRNA levels in the epileptic samples.

Conclusion: Our findings suggest that certain genes become differen-tially regulated by DNA methylation in epilepsy.

p082EVOKED HIGH FREQUENCY OSCILLATIONS IN THEHUMAN HIPPOCAMPAL FORMATIOND. Fabo*, E. Toth�, A. Sakovics*, L. Er}oss�, and I. Ulbert§

*Natl. Institute for Neuroscience, Budapest, Hungary; �PeterPazmany Catholic University, Budapest, Hungary; �NationalInstitute of Neuroscience, Budapest, Hungary; and §Institute forPsychology, Hungarian Academy of Sciences, Budapest,Hungary

Purpose: Cortical electrical stimulation (CES) is an approved therapyfor drug resistant focal epilepsies. Despite the advanced usage of intra-cortical evoked potentials (iEP) the neuronal circuit mechanisms of CESare poorly understood. We examined the effect of CES under generalanesthesia in the hippocampal formation (HF) of five temporal lobe epi-lepsy (TLE) patients.

Method: We used laminar multielectrodes to record local field potential(LFP), multiple unit activity (MUA), current source density (CSD) andspectral activation of iEPs elicited by singe pulse (SPS) and train (TrS),subdural cortical electrical stimuli (0.1ms; 5–15mA; 0.5Hz and 50Hz).High frequency oscillation packages, ripples, were detected by semi auto-matic methods.

Result: High frequency oscillations (ripple and fast ripple) was associ-ated to bi- or tri-phasic iEPs were elicited by SPS in the HF stimulatingthe temporo-basal areas. The central frequencies of different ripples were

25

Abstracts


100, 150 and 250Hz. Ripple activity was elicited with high probability(60–98%). Similar but higher power ripples and fast ripples associated toafter discharges after TrS.

Conclusion: We conclude that CES iEPs contain abundant amount ofripples and fast ripples. The evoked ripple activity raises questions aboutthe long-term effects of CES in the temporal lobe.

p083THE EXPRESSION OF MIR-132 ASSOCIATED WITHCREB IN EPILEPSYH. WangThe Second Affiliated Hospital Chongqing Medical University,Chongqing, China

Purpose: Temporal lobe epilepsy (TLE) is a common and often neuro-logical disorder. TLE is often associated with the formation of excitabil-ity of abnormal circuit. MicroRNAs (miRNAs) are small non-codingRNAs that play essential roles in synaptic development, synaptic plastic-ity and cytoskeletal reorganization. Mir-132 that is a CREB-adjustingprotein can increase density and length of dendritic spines, and increasefrequency of miniature excitatory post-synaptic currents (mEPSCs) anddecrease synaptic depression through inhibiting P250GAP that is a fam-ily number of Rho GTPase.

Method: We in a rat model of epilepsy and in the human TLE separatelymeasured mir-132 expression with real-time PCR and P-CREB that is anactive form of CREB with western blot and immunohistochemistry tech-nology.

Result: Were that mir-132 is up-regulated at 24 h after initiation of theseizure in the rat model of TLE, and this coincided with up regulation ofP-CREB expression. But at the rest of time points in the rat model of epi-lepsy and in the human TLE mir-132 is down-regulated, and this does notcoincide with up regulation of P-CREB expression.

Conclusion: These results show that P-CREB is likely to partly adjustmir-132 expression especially at the acute stage of epilepsy, but atchronic stage and in the human TLE mir-132 is likely to be affected byother factors. The change of up regulation and down regulation of mir-132 is likely to be easier to form the excitability of abnormal circuit. Sim-ilar to the alternate use of latrunculin A and jasplakinolide induce epilep-tic seizures and a long-term increase in neuronal excitability.

p084THE EXPRESSION OF LIM KINASE1 AND ASSOCI-ATED ACTIVE FORM IN HUMAN AND RAT TEMPO-RAL LOBE EPILEPSYX. Yang, and X. WangThe Second Affiliated Hospital of Chongqing MedicalUniversity, Chongqing, China

Purpose: Epilepsy is a common and often neurological disorder. Epi-lepsy is often associated with formation of excitatory circuit, includingabnormal form of dendrites and axons, but the exact mechanism remainsunknown. Lim kinase1 (limk1) is an associated cytoskeletal protein,phosphorylated at the site of threonine 508, and then by phosphorylatingcofilin affects dynamics of cytoskeleton and synaptic plasticity. So weinfer that limk1 and its active form phospho-limk1 (p-limk1) may involvein the pathogenesis of epilepsy by affecting cytoskeletal reorganizationand synaptic plasticity.

Method: Here, we investigated expression of limk1 and p-limk1 byimmunohistochemistry and western blot analysis in a rat model of tempo-ral lobe epilepsy (TLE) as well as in human TLE.

Result: In the rat model of TLE, p-limk1 expression was up-regulated at6h, 72h, 30d and 60d after initiation of the seizure, corresponding withup-regulated limk1 at 6h, 72h, 7d, 14d, 30d and 60d. Moreover, in human

TLE the down-regulated limk1 did not correspond with up-regulated p-limk1.

Conclusion: These results may reflect limk1 expression as substancebasis is not a leading reason for affecting p-limk1 expression in humanTLE, probably impressed by some activators of limk1, such as P21-acti-vated kinase (PAK) and Rho-associated coiled-coil domain kinase(ROCK). These indicated limk1 and p-limk1 are likely to involve in path-ogenesis of epilepsy by affecting cytoskeletal reorganization, and differ-ent predominant reasons may affect cytoskeletal reorganization andsynaptic plasticity by affecting at different stage and severity of TLE.

p085A MATHEMATICAL MODEL OF EPILEPSY: SYNAPTICREGULATION ACTS AS AN ANTI-EPILEPTIC REGU-LATORY MECHANISMA. Peterson*, I. Mareels*, and M. Cook�

*University of Melbourne, Parkville, Vic., Australia; and �TheUniversity of Melbourne, Melbourne, Australia

Purpose: The spread of seizure-like behaviour through the cortex isfacilitated not only by hyper-excitable, hyper-synchronous neuronal pop-ulation firing, but by overcoming the regulatory mechanisms of the brain,such as feedback, feed-forward and surround inhibition. These controlmechanisms attempt to stabilise such pathological behaviour. We suggestan additional network regulatory mechanism in the form of a ‘shunting’effect based on endogenous synaptic regulation of input currents, animportant neurophysiological function whose mechanism is difficult toincorporate in macroscopic models of brain dynamics.

Method: A mathematical neural model is modified to include more real-istic synaptic dynamics as opposed to previous models which use simpli-fied synapses. This is a more realistic description of synaptic behaviourthat has a significant effect on the overall network dynamics. A nonlinearsummation (as opposed to a linear one) of the synaptic currents is intro-duced that incorporates local feedback from the membrane potential andan ‘active’ time constant that varies inversely with the amount of input ordrive to the network. The result is a more physiologically detaileddescription of the synaptic current produced by post-synaptic potentials.The states of the new system are found and an analysis is performed. Thestability of the system is determined and an exploration of pertinentparameters, namely the network input and network balance (inhibitory/excitatory), highly relevant to epileptogenesis is produced. These resultsare then compared to that of the original model with simplified synapsesand the differences interpreted physiologically.

Result: The dynamics and oscillatory properties of the more detailedmodel differ significantly from the previous model. This is largely due tothe ‘shunting’ effect of synaptic regulation, which acts as a network con-trol mechanism. In particular, within the same parameter ranges for thenetwork input and balance, oscillatory behaviour is suppressed.

Conclusion: Synaptic regulation of network behaviour is an importantneuro-physiological function whose mechanisms of synaptic currenttransmission and homeostatic tendencies should not be neglected in neu-ral models of epilepsy, particularly when examining seizure localisation,spread and termination.

p086DEEP BRAIN STIMULATION EARLY DURING EPILE-PTOGENESIS MODIFIES DISEASE PROGRESSION INTHE HIPPOCAMPUSB. Van Nieuwenhuyse*, K. Vonck*, R. Raedt*, A. Meurs*,W. Wytse�, and P. A. J. M. Boon**Ghent University, Ghent, Belgium; and �SwammerdamInstitute of Life Sciences, Amsterdam, The Netherlands

26

Abstracts


Purpose: Despite promising DBS results, the mechanism of action, thelong-term effects and the possible anti-epileptogenic properties of DBSremain undetermined. In this animal experimental study, we evaluatedthe effect of DBS on the development of spontaneous seizures in the kai-nic acid rat model.

Method: Rats were implanted with a bipolar DBS electrode in theright hippocampus and a bipolar EEG recording electrode in both hip-pocampi. 24 hours after kainic acid (KA) induced status epilepticus(SE), one group (n=6) was subjected to short term DBS (ST-DBS)(poisson distributed stimulation (PDS), 130 PPS, 100ls PW, 100lA)of 1 week, a second group (n=7) was subjected to long term DBS (LT-DBS) (PDS, 130 PPS, 100ls PW, 100–400lA) of 10 weeks. A controlgroup (n=9) received sham stimulation (SHAM). EEG was recordedcontinuously during 14 weeks in the LT-DBS and SHAM group. In theST-DBS group, EEG was recorded continuously during the first 8weeks of the experiment.

Result: Development in daily seizure frequency is significantly differ-ent between LT-DBS and SHAM. Seizure frequency in the SHAM grouprose from 0.1 € 0.1 seizures/day in week 1 to 26.6 € 3.1 seizures/day inweek 14. This rise in seizure frequency was significantly reduced in theLT-DBS group (0.5 € 0.1 seizures/day in week 1 to 1.2 € 4.14 € 1 sei-zures/day in week 14). No differences between SHAM and ST-DBS ratswere observed.

Conclusion: LT-DBS initiated shortly after SE reduces the developmentof spontaneous seizures. These results show that temporary treatmentwith hippocampal DBS can affect disease progression.

p087SUDEP FOLLOWING STATUS EPILEPTICUSA. Lacey*, M. I. Rees�, P. Smith�, and R. H. Thomas**Swansea University, Swansea, UK; �Institute of Life Science,Swansea, UK; and �Wales Epilepsy Research Network,Swansea, UK

Purpose: Status epilepticus (SE) is a life-threatening complication ofepilepsy and a medical emergency. However, for some, an episode of SEis their first presentation of epilepsy.

Method: Using the Secure Anonymised Information Linkage (SAIL)databank at we scrutinised primary care records in Wales for patientswho have had an episode of SE. In order to better understand the progno-sis of epilepsy following SE we looked at contemporaneous comorbidi-ties and mortality records.

Result: Since 1991 there have been 2.9/100,000 episodes of SErecorded in Wales. 732 people were identified as having SE and therewere 174 deaths recorded; 15.5% were within six months of SE. Intotal there were 13 potential cases of SUDEP. 12.8% of people whofirst presented in SE (and later died) had epilepsy as a cause of deathcompared to 3.1% of those who had pre-existing epilepsy prior to SE(p>0.02). 2.5 times more people presenting with SE without knownepilepsy were known to have a brain tumour (n=10, 3.6%). On Sevenoccasions more people with epilepsy had a change of medicationwithin a month of SE (32%) than people who had SE without a priordiagnosis of epilepsy (4%; p>0.0001).

Conclusion: This nationwide study identifies that SE as a first presenta-tion of epilepsy is associated with an increased risk of SUDEP althoughnot all cause mortality. We believe that SE occurring from pre-existingepilepsy may be triggered by poor medication concordance or change indrug regime, rather than a new symptomatic cause such as tumour orstroke.

p088LENTIVIRAL VECTOR-DELIVERED SMALL INTER-FERING RNA TARGETING TO HIF-1A GENE EFFECTON MDR1B GENE EXPRESSION IN RAT ASTROCYTESMODEL INDUCED BY CORIARIA LACTONEL. Chen*, T. Zeng*, Y. Li�, and D. Zhou�

*West China Hospital of Sichuan University, Chengdu, China; �

Chengdu, China; and �West China Hospital, Chengdu, China

Purpose: Over-expression of multidrug resistance gene (MDR1) is animportant mechanism of refractory epilepsy. Epileptic seizure may leadto accumulation of hypoxia-inducible factor-1a (HIF-1a) in hippocampusand temporal lobe. MDR1 gene-promoter contains a functional HIF-1abinding site, which is known as the classical hypoxia response element(HRE). Thus, we have the hypothesis that expression of Pgp is up regu-lated by HIF-1a in refractory epilepsy, which has been observed in cancerpharmacoresistance research. So the objective of this study is to explorethe correlation of Pgp expression with HIF-1a in refractory epilepsy ratmodel.

Method: We established a kindling model of MDR temporal lobe epi-lepsy (TLE) by intramuscular injection Sprague-Dawley rat with coriarialactone (CL), and served normal SD rats with normal sodium (NS) injec-tion as control group. The fragment gene carrying rat HIF-1a siRNA wascloned into lentiviral vector, identified with PCR and sequencing analysis.The correct reconstructed lentiviral vector was packaged into HEK 293cells, then amplified and purified and injected into rat lateral cerebral ven-tricle. The expression level of MDR1b and its translational product P-gly-coprotein (Pgp) were monitored with Real-time PCR and Western-blotanalysis before lentiviral vector transfection and after (at different times).

Result: The recombinanted lentiviral vectors target to rat HIF-1a weresuccessfully constructed and packaged. It can infected the rat astrocyteswith higher efficiency. For the rat model, the mRNA and protein levels ofHIF-1a increased significantly (P<0.05) in hippocampus and temporallobe, compared with control group. An accordant result was obtained inthe expression of Pgp. After reconstructed lentiviral transfection, the levelsof HIF-1a and Pgp decreased at the same time in the same brain region.

Conclusion: Our study demonstrates that HIF-1a expression increasedin accordance with Pgp in hippocampus and temporal lobe of refractoryepilepsy rat model induced by CL. And the recombinant lentivirus deliv-ered Small Interfering RNA targeting to HIF-1a gene can suppressed notonly the overexpression of HIF-1a, but also the expression of MDR1b inmodel brain without obvious cell toxicity. So that HIF-1a may take anmore important role in the mechanism of refractory epilepsy. furthermore, this study may provide a promising technique for refractory epi-lepsy remedy.


p089ELECTROGRAFIC SEIZURES AND PERIODIC EPILEP-TIFORM DISCHARGES IN PATIENTS WITH POST-ANOXIC COMAE. Altindag*, Z. V. Okudan�, B. Baykan�, O. Gungor Tuncer *,B. Aksay Koyuncu*, S. Tavukcu Ozkan *, and Y. Krespi**_Istanbul Florence Nightingale Hospital, Istanbul, Turkey; �

Istanbul Bilim University, Istanbul, Turkey; and �IstanbulUniversity Istanbul Medical Fakulty, Istanbul, Turkey

Purpose: We aimed to examine the predictors and prognostic value ofelectrographic seizures (ESZs) and periodic epileptiform discharges(PED) of post-anoxic coma patients in intensive care unit (ICU).

27

Abstracts


Method: The clinical, EEG and neuroimaging findings of consecutiveanoxic comatose patients due to cardiac arrest were studied between2009 and 2011. EEG data was reviewed by 2 investigators indepen-dently.

Result: Seventeen patients (7 F; mean age: 59.8€16.9) were admitted toour study. The mean duration of hospitalization was 54.6 days. The out-come included death in 7 patients, severe neurological deficits in 6patients. Thirteen patients had Glasgow Coma Score.

Conclusion: MSE and various electrographic patterns detected inpatients with post-anoxic coma could not predict the mortality. Largerprospective studies are warranted to determine the impact of these pat-terns more precisely.

p090STATUS EPILEPTICUS, A HOSPITAL BASED SYS-TEMIC CASES REVIEW IN SOUTHERN TAIWANC. LoNational Cheng Kung University Hospital, Yunlin, Taiwan

Purpose: Little are studied the systemic clinical features of status epi-lepticus (SE) in Southern Taiwan. To have a basic understanding of thesefeatures, including age and sex distributions, SE types, aetiologies, prog-nosis, anatomic correlations, validities of the investigation tools, etc; andto promote further clinical researches in SE, a systemic cases review wascarried out.

Method: Epilepsy cases admitted to the Chiayi Christian Hospital or theNational Cheng Kung University, Douliou branch, during 2001–2011,were reviewed. Inclusion criteria were those who fit current SE definitionsuggested by the ILAE, ie continuous seizures up to 5 minutes withoutstopping, or no return of consciousness to the baseline between 2 or moreconsecutive seizures. Exclusion criteria were those with incomplete med-ical records or poor evidence in suggesting SE.

Result: Altogether 173 patients entered the systemic cases review. Maleto female ratio was 103:73 (59.5% vs 40.5%). Most patients were in theirseventies [40/173 (23.1%)] and sixties [37/173 (21.4%)]. 145 patientshad convulsive SE, and 28 had non-convulsive SE. The leading causes inSE were cerebral vascular disease [59/173 (34.10%)], metabolic disor-ders [48/173 (27.7%)], and poor seizures control [43/173 (24.8%)]. Fron-tal and temporal lobe lesions were the leading damages seen in images.Epileptiform discharges did not always correlate the lesions found inimages.

Conclusion: Several issues raised that need further study, including thediscrepancy in sex distribution; the correlation between EEG and imagesfindings, the mechanism causing higher risks in having SE with frontal-temporal lesions, and the impact of co-morbidities in causing SE in theelderly.

p091IV LACOSAMIDE AS THERAPEUTIC OPTION FORREFRACTORY STATUS EPILEPTICUS BEFORE COMAINDUCTIONE. Santamarina, M. Toledo, M. Sueiras, M. Raspall, N. Allouti,E. Lainez, M. Vicente, J. Conill, M. Roig, and X. Salas-PuigVall d¢Hebron University Hospital, Barcelona, Spain

Purpose: Refractory status epilepticus (RSE) is a neurological conditionthat often requires sedation to be controlled. IV Lacosamide is a novelantiepileptic drug that may provide some benefits in RSE before inducingcoma.

Method: We reviewed the data concerning the efficacy and safety of IVLacosamide for RSE in 21 consecutive patients.

Result: Patients¢ average age was 60 [14–85] years-old. Eleven patientshad preexisting epilepsy. The most frequent RSE was convulsive in 70%.Seizure semiology was most likely complex partial (11) or generalizedtonic-clonic (6). The RSE was classified as remote symptomatic (9),acute symptomatic (8) and cryptogenic (3). The most frequent etiologywas the vascular lesion (50%). The IV Lacosamide was started with aninitial bolus of 200 mg, and then followed by maintenance or individual-ized daily dose increases, depending on the electroclinical response.Lacosamide was used as a second drug (1), third drug (7) or fourth drug(12). Overall, RSE cessation was achieved in 55% of patients, of whom40% within 72 hours. The highest rates of success were obtained by com-bining benzodiacepines, levetiracetam and Lacosamide. Four patientsdied during the RSE and six required further sedation. Somnolence andgastrointestinal symptoms were all the adverse events attributable tolacosamide in two patients. IV LCM was switched to equal doses per oralat hospital discharged. Five patients died remotely and 10 have remainedseizure-free during the follow-up (5 months [1–20]). IV LCM can be anoption for RSE as a previous step to sedation in the protocol of treatmentof the RSE.

p092SELECTIVE LENTIVIRAL MEDIATED TARGETINGOF GLIA CELLS IN THE CENTRAL NERVOUS SYSTEMM. Fassler, I. Weissberg, N. Levi, A. Monsonego, R. Taube, andA. FriedmanBen-Gurion University of the Negev, Beer Sheva, Israel

Purpose: In a complex tissue of the central nervous system (CNS),cell cross-talk is essential to preserve normal functions. Current toolsfor dissecting the molecular mechanisms that mediate cell-cell interac-tions within the brain are technically challenging, time consuming anddifficult to control. In this study we report the establishment and vali-dation of a lentiviral-mediated gene-targeting platform to specific cellsin the CNS.

Method: Using lentiviral-mediated gene-targeting platform that com-bines unique features of self-inactivated lentiviruses that promote stablegene delivery into non-dividing cells and efficient display of single-chainvariable region human fragments (scFv) or soluble IgG on the surface ofviral particles.

Result: In vitro, cells that express the receptor-binding domain ofthe SARS-CoV spike glycoprotein were targeted by engineered sind-bis pseudotyped lentiviruses that incorporate specific scFvFc attach-ment moieties. Additionally, in vitro targeted gene expression toprimary astrocytes was also demonstrated, using engineered lentivi-ruses that incorporate Aquaporin 4 and GLAST IgG. In vivo, lentivi-ral targeting of astrocytes and oligodentrocytes progenitor cells thatexpress the chondroitin sulfate proteoglycan, NG2 was obtained usingviral particles that display an anti-GLAST and anti-NG2 IgG antibod-ies, repectively.

Conclusion: We conclude, that this novel approach will be implementedin the model of epilepsy to study the role of astrocytes in the pathogenesisof the disease and challenge its use as a therapeutic tool.

p093ASYMMETRIES OF SLEEP SPINDLES IN HUMAN EPI-LEPSY WITH TEMPORAL OR FRONTOTEMPORALFOCUSA. Kyrozis, C. Moschovos, E. Tsoukas, A. Bonakis, D. Pandis,A. Ghika, I. Evdokimidis, and N. KalfakisUniv. Athens, Athens, Greece

28

Abstracts


Purpose: It is unclear whether temporal lobe epileptic foci can affectsleep spindles, which are generated in extratemporal thalamo-cortical cir-cuits. We tested for such effects, the detection of which may have patho-physiologic and clinical diagnostic implications.

Method: Sleep EEG recordings of 6 cryptogenic epilepsy patients withright temporal or frontotemporal focus (TR), 6 with left temporal orfrontotemporal focus (TL) and 12 controls with non-epileptic paroxysmalevents and normal MRIs were used. Central sleep spindles were detectedby a custom-made computer algorithm (MATLAB software). Spectralpower, peak frequency, inter-channel transfer function estimate (TFE)angle (reflecting phase difference) and inter-channel coherence wereassessed.

Result: No significant inter-hemispheric differences were found forpeak frequency and spectral power. Spindles recorded at frontal elec-trodes appeared a few milliseconds earlier on the side of the focus in 11of 12 epilepsy cases. The lateralization was highly significant (mean€-SEM TFE angles from F3 to F4: TR: + 0.212€0.055; TL: - 0.204€0.077,Tukey test p=0.0057). Coherence was also higher on the side of the epi-leptic focus [Coh (F3Fz)–Coh (F4Fz): TR: -0.055€0.06; TL:+0.09€0.025, Tukey test p=0.028], implying greater synchronization onthe side of the focus.

Conclusion: Temporal lobe epilepsy promotes initiation and synchro-nization of sleep spindles on the side of the focus. The observedchanges may be the result of network modifications on the side ofthe focus and/or altered hippocampal-frontal networks that modulatesleep oscillations. The results suggest the possibility of using sleepspindles for the detection of the presence and side of an occult epi-leptic focus.

p094WIRELESS INSTANTANEOUS ADENOSINE RECORD-ING DURING KAINIC ACID-INDUCED SEIZURE INRAT: WINCS APPLICATIONY. Shon*, and S. Lim�

*Yeouido St. Mary's Hospital, The Catholic University of Korea,Seoul, Korea; and �St. Mary's Hospital, The Catholic Universityof Korea, Seoul, Korea

Purpose: Adenosine, as the brain's endogenous anticonvulsant, is con-sidered to be responsible for seizure arrest and postictal refractoriness.We performed ictal EEG & co-monitoring of neurotransmitter recordingby WINICS (wireless instantaneous neurotransmitter concentration sys-tem, fast-scan cyclic voltammetry based) in the acute hippocampal sei-zure model of rat.

Method: Rats (n=18) were implanted with bipolar hippocampal depthelectrodes and a cannula for the injection of KA (1 mcg/4min) in the righthippocampus (CA3) under urethane anesthesia. WINCS recording elec-trode was inserted in left hippocampus (mirror site of R HC). Simulta-neous recordings of EEG (8 channels) and WINCS were performedcontinuously after KA induced limbic status epilepticus (usually 10–15min after injection).

Result: There were two patterns of adenosine release during the KAinduced limbic status epilepticus. First, intermittent and phasic release ofadenosine (n=2) was clearly observed only during the early period ofslow, large-amplitude spike and wave, but not at the low-amplitude fastor repetitive spikes among the recurrent ictal EEG pattern. Second, therewere a rapid adenosine and dopamine release immediately at the timepoint of sudden, transient disappearance of polyspike or spike-wave dis-charges in the EEG (n=7).

Conclusion: Our study shows that the slow phase of spike-wavecomplex or its transient disappearance after prolonged status epilepti-cus may be linked to a suppression of neuronal hyperexcitabilityvia adenosine release. We may suppose that the local delivery of

adenosine into the ictal focus is likely to be effective in the controlof intractable seizures.

p095ALPHA-LACTOALBUMIN, A WHEY PROTEIN RICH INTRYPTOPHAN, IS EFFECTIVE IN RODENT MODELSOF SEIZURES AND EPILEPTOGENESISG. De Sarro*, F. Scicchitano*, R. Citraro*, S. Chimirri*,P. Mainardi�, E. Perucca�, and E. Russo**University of Catanzaro, Catanzaro, Italy; �University ofGenova, Genova, Italy; and �Pavia, Italy

Purpose: ALAC (alpha-lactoalbumin), a whey protein rich in trypto-phan, shows protective activity in preclinical models of seizures and epi-lepsy and was recently associated with improved seizure control inpatients with drug-refractory epilepsy.1,2 We evaluated the potentialactivity of ALAC in some other rodent models of seizures and epilepto-genesis and we explored a possible mechanism of action.

Method: The effects of ALAC (oral administration) were tested in twostandard epileptogenesis protocols, namely the pilocarpine post-statusepilepticus model in mice and the WAG/Rij rat model of absence epile-ptogenesis.2,3 The mechanism of action was investigated by assessing theeffects of ALAC in two seizure models (NMDA and PTZ-induced sei-zures) including D-serine co-administration4.

Result: ALAC showed protecting properties in both models of epilepto-genesis, reducing spontaneous seizures development. In acute seizuremodels, ALAC possessed antiseizure properties at some of the dosestested (PTZ-seizures: 50% seizure-reduction at 250mg/kg; NMDA-sei-zures: 90% reduction at 250 and 500mg/kg). When a dose of D-Serineineffective per se was co-administered with ALAC, ALAC effects weresignificantly reversed in both models.

Conclusion: ALAC is active in experimental models of seizures andepileptogenesis. Its effects are likely mediated by the inhibition ofNMDA receptors at the glycine binding site, possibly secondarily to thein-vivo enzymatic conversion of ALAC-generated tryptophan to kynure-nic acid. However, other mechanisms of action contributing to ALACeffects cannot be excluded.

References:1 Mainardi, et al., 2008. Med Hypotheses 70, 876–9.2 Citraro et al., 2011 Epilepsy Res 95, 60–9.3 Russo et al., 2011 Epilepsia 52, 1341–50.4 Russo et al., 2004 Neuropharmacology 46:865–78.

p096THECX32 GENE EXPRESSION IN BRAIN FOCI OFPATIENTS WITH REFRACTORY EPILEPSYW. Lin, and L. Zhangthe first hospital of Jilin University, 130021, China

Purpose: In order to study CX32 gap junction gene expression in thebrain epileptic foci of patients with refractory epilepsy, and lay the foun-dation for clinical research and treatment of refractory epilepsy.

Method: 24 patients with refractory epilepsy that have undergone sur-gery in the experimental group, 10 patients with traumatic brain injurythat have undergone emergency surgery in control group. epileptic brainfoci tissue were removed from surgery, immunohistochemistry andimmune electron microscopy methods were used to observe CX32expression in both group.

Result: Immunohistochemistry results showed that CX32 expression inthe experimental group was higher than the control group (p<0.001),There are more colloidal gold particles labelling CX32 on the membranes

29

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of nerve cells in the brain tissue of the experimental group than the con-trol group under electron microscopy (p<0.001).

Conclusion: The expression of CX32 in the epileptic brain foci wasincreased, which may play an important role in the happen and develop-ment of epilepsy.

p097GABAERGIC EXCITATORY MECHANISMS AREINVOLVED IN THE GENESIS OF EPILEPTIC ACTIVI-TIES IN THE CORTEX SURROUNDING GLIOMA INHUMANSG. Huberfeld*, J. Pallud*, M. Levanquyen�, M. Baulac�,F. Bielle�, C. Duyckaerts�, F. Roux§, R. Miles*, and L. Capelle�

*CRICM - UPMC - INSERM - CNRS, Paris, France; �Hpital dela Piti�-SalpÞtri�re, Paris, France; �CHU Pitie-Salpetriere,Paris, France; and §CH Ste Anne, Paris, France; and

Purpose: Brain gliomas are associated with seizures in a majority ofpatients, but their pathophysiology and link with the tumor is stillunclear.

Method: The physiology of the resected tumor and surrounding securitymargin can be explored in neocortical slices providing a novel opportu-nity to explore epileptogenic mechanisms in human tissue.

Result: We found that postoperative glioma tissues of 69% patientsspontaneously generated interictal-like discharges. These events weresynchronized in superficial layers of cortical columns in the neocortexsurrounding glioma areas that presented a tumor infiltration. They werenever recorded in the tumor core or in control tissues. Interictal-likeevents depended on both depolarizing GABAergic and glutamatergictransmission. Interneuron firing preceded them, and Chloride homeosta-sis was perturbed in 65% of pyramidal cells resulting in a depolarizationinduced by GABA. Ictal-like activities could be exclusively generated inthese areas. They were preceded by a long range period characterized bythe progressive emergence of glutamatergic preictal discharges.

Conclusion: These epileptic activities sustained by excitatory effects ofGABA, as those reported in human temporal lobe epilepsies, suggest thatcellular Chloride regulation processes affecting oncogenesis are involvedin the excitatory/inhibitory imbalance causing epileptic activity in peri-tumoral tissue.

p098THE OUTCOME OF ANTIEPILEPTIC DRUG THERAPYIN BENZODIAZEPINE-RESISTANT STATUS EPILEPTI-CUS: A REVIEW OF PUBLISHED CASES AND TRIALSZ. S. Y. YasiryUCL Institute of Neurology, London, UK

Purpose: This work addresses the question of what drug(s) is(are) thenext most effective when benzodiazepines fail to control convulsive sta-tus epilepticus.

Method: A systematic search of literature for the outcome of the use ofphenobarbital, phenytoin, valproate, levetiracetam and lacosamide hasbeen carried out.

Result: Ninety eight papers have been included in the review. The evi-dence base is categorized as level 111, and the use of each drug hasadvantages and disadvantages.

Conclusion: The paper presents a detailed analysis of the publishedpapers and a comparison of these widely-used drug therapies.

Epilepsy Surgery 1Monday, 01 October 2012

p099LATERALIZATION AND LOCALIZATION OF POST-TRAUMATIC EPILEPSY WITH DUAL PATHOLOGYUSING FORAMEN OVALE ELECTRODES: A CASEREPORTH. Henninger*, D. T. Hsieh�, E. N. Eskandar�, and A. J. Cole�

*Maine Medical Partners Neurology, Scarborough, USA; �

Massachusetts General Hospital, Boston, USA; and �MGHEpilepsy Service, Massachusetts General Hospital, Boston, USA

Purpose: Traumatic brain injury is typically multifocal and may consistof bleeding, gliosis, axonal injury, and hippocampal sclerosis. Each ofthese mechanisms may lead to post-traumatic epilepsy. When more thanone possible seizure onset zone is present concomitantly, this is oftenreferred to as dual or multifocal pathology. Foramen ovale electrodes canlateralize and localize mesial temporal lobe epilepsy in cases where clini-cal uncertainty exists.

Method: A 57-year-old left handed man was evaluated for medicallyrefractory epilepsy. Epilepsy began at age 19 following a motorcycleaccident resulting in a left temporal intraparenchymal hemorrhage. MRIdemonstrated marked left temporoparietal encephalomalacia as well asright hippocampal atrophy with increased T2 signal intensity. SurfaceEEG captured several right temporal lobe seizures, however concernabout the role of the left hemisphere lesion led to prior rejection of resec-tive epilepsy surgery.

Results: Bilateral foramen ovale (FO) electrodes were surgically placedfor continuous EEG recording. Six electro-clinical seizures wererecorded with clear onset in the right FO electrodes. Right anterior tem-poral lobectomy was performed resulting in seizure freedom with mini-mal effect on memory.

Conclusion: Post-traumatic epilepsy with dual or multifocal pathol-ogy can present a clinical dilemma, especially if the site of apparentseizure onset is contralateral to the most extensive post-traumaticinjury. When mesial temporal seizure onset is suspected, foramenovale electrode EEG monitoring can provide confirmation of laterali-zation and localization of the seizure onset zone without furtherinvasive monitoring.

p100A PROSPECTIVE LONG-TERM STUDY ON THE OUT-COME AFTER VAGUS NERVE STIMULATION ATMAXIMALLY TOLERATED CURRENT INTENSITY INA COHORT OF CHILDREN WITH REFRACTORY SEC-ONDARY GENERALIZED EPILEPSYA. Cukiert*, C. Cukiert*, A. Lima*, J. Burattini*, C. Forster*,C. Baise�, and M. Argentoni-Baldochi�

*Clinica De Epilepsia De Sao Paulo, Sao Paulo, Brazil; and �

Hospital Brigadeiro, S¼o Paulo, Brazil

Purpose: We report the outcome after VNS in kids with secondary gen-eralized epilepsy, and advance in the discussion of issues rarelyaddressed such as maximal stimuli intensity, seizure worsening, ‘‘honey-moon effect’’, and specific seizure type control rates.

Method: Twenty-four consecutive children with Lennox-Gastaut orLennox-like syndrome under the age of 12 years by the time of surgery,were prospectively included in the study. The generator was turned onusing 0.25mA, 30Hz, 500lsec, 30sec ‘‘on’’, 5 minutes ‘‘off’’ stimuliparameters; current was then increased by 0.25mA every 2 weeks, until3.5mA was reached or adverse effects were noted.

30

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Result: Six kids got an end-of-study (24 months) post-implantationvideo-EEG and their findings were similar to those before vagus nervestimulation. Quality of life and health measures improved in up to 50%(mean=25%) in 20 kids. Attention was noted to improve in 21 out of the24 kids. Final intensity parameters ranged from 2 to 3.5mA(mean=3.1mA). An at least 50% seizure frequency reduction immedi-ately after implantation and with the generator off was noted in 14 out ofthe 24 kids. There were 47 seizures types among the 24 children. An atleast 50% seizure frequency reduction was noted in 35 seizure types and17 seizures types disappeared after VNS. Atypical absence, myoclonicand generalized tonic-clonic seizures were significantly reduced byVNS; tonic and atonic seizures did not improve. Transient seizure fre-quency worsening was noted in 10 of the 24 kids, at a mean of 3.1mA.

Conclusion: Our study showed that VNS was effective in reducing atyp-ical absence, generalized tonic-clonic and myoclonic seizures (but notatonic or tonic seizures) in kids with Lennox-Gastaut or Lennox-like syn-drome. A concomitant improvement in attention level and quality of lifeand health was also noted. Secondary generalized epilepsy might repre-sent a subset of good candidates for VNS.

p101THE EFFICACY OF VNS IN PHARMACORESISTANTEPILEPSY OF TEMPORAL VERSUS EXTRA-TEMPO-RAL LOBE LOCATIONSA. Abubakr*, and I. Wambacq�

*University of Mississippi Medical Center, Jackson, USA; and �

Montclair State University, Bloomfield, NJ, USA

Purpose: This is a retrospective study evaluating the effectiveness ofVNS therapy in patients with refractory epilepsy of temporal versusextra-temporal lobe locations.

Method: The medical records of 31 patients implanted with VNSbetween1998 and 2001 were reviewed. Patients were divided into TLEgroup and extra TLE group based on the epileptogenic foci. Changes inseizures frequency was assessed at one year following VNS implant.Patients with >50% reduction in seizures frequency were consideredresponders to VNS therapy.

Result: Out of 31 patients one died of unrelated cause, and another askedtheir device to be removed due adverse effects. There were 9 patientswith TLE (5 males and 4 females), age range 27–61 yrs, with epilepsyduration of 4–40 yrs, and seizures frequency of 1–450/month and takingan average 2–5 AEDs a day. There were twenty patients with extra TLE(9 males and 11 females), age range 14–62 yrs, epilepsy duration of 8–54yrs, and seizures frequency of 3–900/month and taking 2–4 AEDs a day.Six out of 9 with TLE (66%) and 11 out of 20 with extra TLE (55%) wereconsidered responders to VNS therapy (>50% reductions in seizure fre-quency) at one year following the implant. There was no significant dif-ference between the two groups (P = 0.88).

Conclusion: This observation demonstrates that VNS is an effectivetherapy in patients with either TLE or extra TLE focus and there is no dif-ference in the responder rate between various epileptogenic foci.

p102HEMISPHERECTOMY – AN OPTION ALSO FOR ADO-LESCENT AND ADULT PATIENTSA. Althausen*, U. Gleissner�, C. Hoppe*, R. Sassen*,S. Buddewig*, M. Von Lehe*, J. Schramm*, C. Elger*, andC. Helmstaedter**University of Bonn, Bonn, Germany; and �LVR-Klinik Bonn,Bonn, Germany

Purpose: Hemispheric neurosurgery is an established treatment forsevere epilepsy caused by extended unilateral brain pathology. However,

it is still an unresolved question at which age surgery should best be per-formed. In light of decreasing plasticity and the cumulative impact of sei-zures and anticonvulsants on neurodevelopment, early surgery appearspreferable. This study aimed to determine whether early hemispherecto-my leads to better long-term outcome than surgery at an older age.

Method: We retrospectively investigated the medical, cognitive-behav-ioral and psychosocial long-term outcome (follow-up: 9.4yrs [1.1–19.4])of hemispherectomy as a function of age at surgery (early: <7yrs/interme-diate: 7–16yrs/late: >16yrs) based on a structured postal questionnaire ina large patient sample (N=61/81, return rate: 75%).

Result: Best seizure outcome was obtained for early surgery patients(90% seizure free). Patients with late surgery, however, had higherpre- and postsurgical intelligence and achieved better psychosocialoutcome. Surgery at an intermediate age yielded cognitive-behavioralimprovements most often. Binary logistic regression confirmed higherage at surgery and higher presurgical intelligence as positive predic-tors of postsurgical intelligence; lower presurgical intelligence andpostsurgical seizure freedom predicted intellectual pre-post improve-ments.

Conclusion: Contrary to expectations, we found no evidence for advan-tages of early surgeries regarding postsurgical cognition and achieve-ment. These data do not suggest to postpone surgery but higher ageshould not exclude patients from hemispherectomy. Presurgical intelli-gence serves as indicator of the severity of the disease and the functionalintegrity of the contralateral hemisphere, which determine cognition andeventually psychosocial outcome. Postsurgical improvements are possi-ble, particularly in case of seizure freedom.

p103CHILDHOOD TEMPORAL LOBE EPILEPSY: BEYONDHIPPOCAMPAL SCLEROSISA. M�hlebner-Fahrngruber, M. Schmook, D. Prayer,A. Dressler, G. Kasprian, G. Grçppel, G. Pahs, T. Czech, andM. FeuchtMedical University Vienna, Vienna, Austria

Purpose: Herein, we focused on clinico-pathological variants of child-hood drug-resistant temporal lobe epilepsy (TLE): pre- and postsurgicaldata of 17 patients (14 female; 9 left TLE), who underwent epilepsy sur-gery, were reviewed.

Method: Video-EEG monitoring including sphenoidal electrodes wasanalyzed with regard to clinical lateralizing signs defining the clinicalsymptomatogenic, the seizure onset and the irritative zon. MRI wasreviewed with respect to presence of hippocampalsclerosis, small tempo-ral lobe, blurring of the grey-white matter junction, signal changes of thesubcortical white matter, and thickening of the adjacent cortex. Histopa-thology was routinely processed for histopathology.

Result: Six children had anterior temporo-polar resection. All sixchildren displayed additional FCD IIIa. All six patients had a historyof febrile seizures. In 5/6 the typical MRI changes in temporal lobewere found. All six of them were seizure free after surgery. Fivechildren who underwent anterior temporo-polar resection showed HSwithout FCD IIIa. 2/5 had febrile seizures. Only 1/5 displayed thetypical MRI changes. Outcome was Wieser 1a in 2 children, Wieser2 was found in 1 and Wieser 3 in 2 patients. Six patients underwentselective amygdalohippocampectomy and therefore temporal cortexwas not available. 4/6 had febrile seizures. None of them hadchanges in the temporal lobe on MRI scan. 5 were seizure free aftersurgery, 1 had outcome Wieser 3.

Conclusion: In summary, the combination of certain clinical character-istics, clear-cut signal alterations on MRI scan, sufficient surgical resec-tion as well as certain histopathological diagnosis is associated with afavourable outcome in childhood temporal lobe epilepsy.

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p104CENTROMEDIAN THALAMIC DEEP BRAIN STIMULA-TION FOR THE TREATMENT OF REFRACTORY GEN-ERALISED AND FRONTAL EPILEPSY: A BLINDEDCONTROLLED STUDYA. Valentin*, R. Chelvarajah�, R. Selway�, L. Vico*, R. Garc�aDe Sola�, E. Garcia Navarrete�, and G. Alarcon**King's College London - Institute of Psychiatry, London, UK; �

King's College Hospital, London, UK; and �HospitalUniversitario de la Princesa, Madrid, Spain

Purpose: Deep Brain Stimulation (DBS) of the thalamus is an emergingsurgical option for medically refractory epilepsy sufferers who are notsuitable for resective surgery, or where surgery has failed. In a single-blind within-subject control study, we evaluate the efficacy of DBS ofcentromedian nucleus (CMN) for seizure control as well as quality-of-lifeoutcome in symptomatic generalised epilepsy (SGE), and frontal lobeepilepsy (FLE).

Method: Eleven patients were recruited (8 males, 3 females) at King'sCollege Hospital (London, UK) and Hospital de la Princesa (Madrid,Spain). Six patients had removal of the VNS device before DBS implan-tation. Ages at surgery range from 18 to 51 years (mean 37). Average fol-low-up period is 2 years. Six patients had SGE and five FLE. Seizurediaries were kept by patients/parents prospectively. Patient reported out-come measures (PROMs) were completed at regular time-points.

Result: Among the 6 patients with SGE, 2 patients became seizure freefor more than 4 years, 3 had seizure frequency reduction greater than50% and one had seizure reduction of 37.5%. None of the patients withFLE became seizure free, 2 had a reduction greater than 50% and 2showed no change. PRO questionnaires showed improvement in approxi-mately 50% of patients.

Conclusion: DBS of CMN appears to be effective in improving seizurecontrol and patient related outcomes in patients with generalised epilepsyand possibly in frontal lobe epilepsy.

p105EPILEPSY SURGERY IN NEUROFIBROMATOSIS TYPE1C. Barba*, T. Jacques�, P. Kahane�, T. Polster§, J. Isnard–,F. S. S. Leijten**, C. �zkara��, L. Tassi��, F. Giordano*,M. Castagna§§, A. John�, B. Oz––, N. Streichenberger–,C. Salon�, R. Guerrini*, and H. Cross****Children's Hospital Meyer, Florence, Italy; �Great OrmondStreet Hospital NHS Trust, London, UK; �Grenoble UniversityHospital, Grenoble, France; §Bethel Epilepsy Centre, Bielefeld,Germany; –Hpital Neurologique, Lyon, France; **RudolfMagnus Institute of Neuroscience, UMC Utrecht, Utrecht, TheNetherlands; ��Istanbul University School of Medicine, Istanbul,Turkey; ��Niguarda General Hospital, Milan, Italy; §§Universityof Pisa, Pisa, Italy; ––Cerrahpasa Medical School, Istanbul,Turkey; and ***ILAE Commission Of Paediatrics, London, UK

Purpose: To report on 12 patients with Neurofibromatosis type 1 (NF1)and drug-resistant seizures, who underwent epilepsy surgery and describetheir clinical presentation, outcome and histopathology.

Method: We included in the study patients with NF1 who had under-gone surgery for drug-resistant epilepsy and had at least one year postop-erative follow-up.

Result: We collected 12 patients from eight European epilepsy centers.MRI abnormalities were detected in all patients but one and were unilat-eral temporal in eight, bilateral in one and multilobar or hemispheric in

two. Seizures originated from the temporal lobe in ten patients, from thetemporo-parieto-occipital region in one, and were bitemporal in one. At 1year follow-up eight patients were seizure free, one had worthwhileimprovement and the remaining three had experienced no benefit. Post-operative outcome was available in ten patients at 2 years and in three at5 years, and remained stable in all but one. The most frequent underlyingpathology was dysembryoplastic neuroepithelial tumor (DNET).

Conclusion: Epilepsy surgery can be performed effectively in patientswith NF1 and drug-resistant seizures. In spite of the frequently multifocalnature of the disorder, a single and well-delimited epileptogenic zone canbe recognized. The high prevalence of DNETs in this series might sug-gest that association of this developmental tumor with NF1 is not fortu-itous.

p106LONG-TERM OUTCOME AFTER CALLOSOTOMY ORVAGUS NERVE STIMULATION (VNS) IN CONSECU-TIVE PROSPECTIVE COHORTS OF PATIENTS WITHSECONDARY GENERALIZED EPILEPSYC. Cukiert, A. Cukiert, J. Burattini, and A. LimaClinica De Epilepsia De Sao Paulo, Sao Paulo, Brazil

Purpose: Palliative procedures such as callosotomy or VNS have beenused for treatment of refractory secondary generalized epilepsy. We com-pared the outcome from these palliative procedures in two consecutiveprospective cohorts of patients with secondary generalized epilepsy.

Method: Twenty consecutive patients with refractory secondary gener-alized epilepsy submitted to callosotomy (Group 1) and additional 20patients submitted to VNS were studied (Group 2). Patients with specificetiology (cortical dysplasia, tuberous sclerosis etc) were excluded fromthe study.

Result: MRI showed atrophy in 70% of Group 1 and in 65% of Group2 patients; non-specific gliosis was present in the remaining patients.All patients had multiple seizure types. Both procedures were similarlyeffective regarding the control of atypical absences and generalizedtonic-clonic seizures, and both were not effective in controlling tonicseizures. Callosotomy was very effective in reducing atonic seizure'sfrequency, while VNS was ineffective. On the other hand, callosotomywas not effective in reducing myoclonic seizures, while VNS did so.Rupture of secondary bilateral synchrony was noted in 85% of Group1 patients; there was no EEG modification after VNS in group 2.Attention improvement was equally noticed in both Groups. All butone Group 1 patients disclosed an acute callosal disconnection syn-drome immediately postoperatively, lasting for up to 3 weeks. Longerhospital stays (including ICU) and blood transfusion were characteris-tics of Group 1 patients only.

Conclusion: Both procedures were effective in treating patients withrefractory secondary generalized epilepsy. Specific seizure typesresponded differently to each treatment.

p107BELGRADE EPILEPSY SURGERY PROGRAM: EARLYOUTCOME OF THE FIRST 35 OPERATED PATIENTSD. V. Sokic*, V. L. Bascarevic�, A. J. Ristic*, N. M. Vojvodic*,A. Parojcic�, S. Lavrnic§, L. Brajkovic–, M. M. Kovacevic�,S. M. Jankovic�, and B. Djurovic�

*Clinic of Neurology Clinical Center of Serbia, University ofBelgrade School of Medicine, Belgrade, Serbia; �Clinic ofNeurosurgery, Clinical Center of Serbia, University of Belgrade,School of Medicine, Belgrade, Serbia; �Clinic of Neurology,Clinical Center of Serbia, Belgrade, Serbia; §Center forMagnetic Resonance, Clinical Center of Serbia, Belgrade,Serbia; and –Institute of Nuclear Medicine, Belgrade, Serbia

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Purpose: Although approximately 200 patients underwent surgery formedically intractable epilepsy between 1975 and 1995 in Belgrade, epi-lepsy surgery program was temporarily interrupted for almost 15 years.Contemporary Belgrade Epilepsy Surgical Program was restarted in2006.

Method: Noninvasive presurgical evaluation was performed in 281pharmacoresistant epilepsy patients and included 5–10 days video-EEGtelemetry, 1.5 T MRI with appropriate angulation, and neuropsychologi-cal testing in all, and interictal PET and/or interictal/ictal SPECT in 19%of patients. Indication for operation was established if the acquired datashowed high concordance.

Result: Surgery was performed in 35 (12%) patients: left side anteriortemporal lobectomy with amigdalo-hippocampectomy in 21 (60%), andright side in 13 (37%) patients. Lesionectomy in right frontal lobe wasperformed in 1 patient. Histology showed hippocampal sclerosis in 22,dual pathology in 5, focal cortical dysplasia in 4, glioma in 2, DNET in 1and cavernoma in 1 patient. Perioperative complications occurred in 10(28%) patients and included dysphasia and dyslexia without permanentradiological infarction (4), hemiparesis (2), infection (3), and amnesia(1). All complications (except hemiparesis due to brain infarction in 2patients) were transitory. Four patients had GTC seizures after surgeryand in 2 of them seizures continued to occur. Seizure remission wasobtained in 33 (94%) patients during 3 to 65 (median: 11) months of fol-low-up. New onset psychosis (3), depression (1) and anxiety (1) occurredafter surgery but responded to appropriate therapy.

Conclusion: Early surgical outcome in patients with pharmacoresistant,predominantly temporal lobe epilepsy is favorable. Complications arereasonably rare.

Epilepsy Surgery 2Monday, 01 October 2012

p108SURGICAL AND HARDWARE COMPLICATIONS TOVAGAL NERVE STIMULATION FOR DRUG RESIS-TANT EPILEPSY. A LONGITUDINAL SINGLE CENTRESTUDY OF 143 PATIENTSH. Kahlow, and M. OlivecronaUniversity Hospital Umea, Umea, Sweden

Purpose: To longitudinally study surgical and hardware complicationsto vagal nerve stimulation (VNS) treatment in patients with drug resistantepilepsy.

Method: In a longitudinally retrospective study we analyzed medicalrecords of 143 patients (81 men and 62 women) whom between 1994 and2010 underwent implantation of VNS-device for drug-resistant epilepsy.The mean follow up time was 62 € 46 months, the total number of patientyears was 738.

Result: 251 procedures were performed in 143 patients (76 stimulatorreplacements). 24 patients (16.8%) were afflicted by complicationsrelated to surgery and 24 patients (16.8%) suffered from technical mal-functions. Surgical complications were: superficial infection in 5patients, deep infection needing explantation in 5, vocal cord palsy in 8,which persisted in at least 1 patient over one year and other complicationsin 8. Hardware related complications were: lead wire fracture in 17, dis-connection in 4, spontaneous turn-off in 2 and stimulator malfunction in2. A tendency though, not statistically significant, was that the frequencyof infections around the stimulator seemed to increase with the number ofstimulator replacements.

Conclusion: The complication rate and the severity of the complicationsto VNS surgery are in an acceptable range. VNS can safely be used as anad on therapy in patients with drug resistant epilepsy not suitable for

resective surgery or failures of the same. There seems to be a tendency ofan increased infection rate with the number of stimulator replacements.This would stress the importance of longer battery life times or the needfor rechargeable devices.

p109LENNOX-GASTAUT SYNDROME AND CALLOSOTO-MYA IN ADULTHOODM. Herbas Rocha*, J. D. D. Del Castillo Calc�neo�, M. Alonso-Vanegas*, D. San Juan Orta�, and B. A. Sandoval Bonilla§

*Instituto Nacional de Neurolog�a y Neurocirug�a ManuelVelasco Suarez, Mexico city, Mexico; �Angeles PedregalHospital, Mexico City, Mexico; �National Institute of Neurologyand Neurosurgery, Mexico City, Mexico; and §InstitutoMexicano de Seguro Social, Mexico City, Mexico

Purpose: The Lennox-Gastaut syndrome (LGS) is one of the mostsevere epileptic encephalopathies of childhood that extends into adult-hood. We show the sociodemographic characteristics and surgical out-come of callosotomy in adults with SLG.

Method: Adults with epilepsy were identified SLG of either sex under-going open callosotomy through the Priority Program Epilepsy and theNeurosurgery Department at National Institute of Neurology and Neuro-surgery from January 2003 to October 2011.

Result: A total of 21 adult patients with LGS submitted to callosotomy,7 women (33%) and 14 males (67%), mean age 25 € 7 years (range 14 to39 years), with a mean age at the time of onset of their illness than 4 years(range 3 months to 11 years) and mean duration of epilepsy of 23 years(range 11 to 38 years). The seizures most frequently found in patientswere: 66.6% atypical absence (14), tonic 57.7% (12), atonic 52.3% (11),complex partial seizures 42.8% (9). All patients underwent 2/3 anteriorcallosotomy. The prognosis at 12 months was; 3 patients were in class A(14.2%), 12 patients in class B (57.14%), 4 class C patients (19%) and 2in Class D (9.5%).

Conclusion: Surgical callosotomy of the anterior 2/3 in adults with LGSis a safe and effective procedure for control of seizures, especially dropattacks and generalized tonic-clinic seizures. Severe mental retardationdoes not affect the clinical outcome and should not be considered a con-traindication. Structural brain abnormalities didn¢t show any effect on theoutcome.

p110POSTOPERATIVE RESOLUTION OF HYPOTHALAMICHAMARTOMA IN A PATIENT WITH GENERALIZEDEPILEPSYN. Cengiz, A. Dagcınar, and K. AkpınarOndokuz Mayıs �niversitesi, Samsun, Turkey

Purpose: A 23-year-old rihgt handed man with typical features of Len-nox–Gastaut syndrome and epilepsy due to hypothalamic hamartomaunderwent successful endoscopic resection with seizure freedom. Ha hadhistory of epileptic seizures since 6 years of age.

Method: The diagnosis of a hypothalamic hamartoma had been madeby magnetic resonance imaging (MRI) of brain . He had received previ-ous gamma knife therapy of the hypothalamic hamartoma at 22 years ofage, which did not help his seizures. At the time of presentation for sur-gery, he was having multiple daily seizures, including gelastic seizures,atonic seizures and generalized tonic-clonic seizures. He had failed 4 an-tiepileptic drugs previously.

Result: His electroencephalogram showed slow generalized spike-and-wave discharges at 1–2-½ hertz as well as multifocal epileptiform dis-charges and abnormal slow background, consistent with and typicalfor Lennox–Gastaut syndrome . Ictal - photon emission computed tomog-

33

Abstracts


raphy performed during typical gelastic seizures demonstrated hyperme-tabolism in the hamartomas, hypothalamic region without cortical or cer-ebellar hypermetabolism .

Conclusion: The patient underwent resective surgery and has been freeof seizures. (8 months follow-up). After operation his EEG was normal.

p111VAGUS NERVE STIMULATION FOR MEDICALLYREFRACTORY EPILEPSY: OUR EXPERIENCE IN ATERTIARY EPILEPSY CENTER AT THE UNIVERSITYOF SEVILLEP. M. Martinez*, M. Caballero*, C. M. Quesada*, R. Vazquez*,M. Oliver�, Y. Chocron�, and M. D. Jimenez**University Hospital Virgen del Rocio, Sevilla, Spain; and �

Hospital Virgen del Rocio, Seville, Spain

Purpose: To evaluate long term outcomes in patients treated with vagusnerve stimulation (VNS).

Method: Our experience with VNS at the University Hospital Virgendel Rocio is comprised of 6 patients with a mean age of 23.8 years and amean duration of epilepsy of 10 years. These patients have been diag-nosed with cryptogenic epilepsy (2 patients), epileptic encephalopathysecondary to perinatal anoxia (3 patients) and hemiconvulsion-hemiple-gia-epilepsy syndrome (1 patient). All patients underwent a comprehen-sive presurgical evaluation and were found to be unsuitable candidatesfor resective epilepsy surgery. Mean post-implantation follow-up is 31months. Efficacy of treatment in terms of reduction in number of seizuresand referred side effects was assessed after the implantation of a VNS.

Result: A greater than 50% reduction in seizure frequency (66%) wasachieved. Two of the patients (34%) did not experience any improvementafter VNS implantation. One patient (17%) had the device removed afterexperiencing hoarseness of voice. After implantation, the average num-ber of hospital admission/ER visits days was significantly decreased.

Conclusion: VNS is an effective and relatively safe adjunctive therapyfor patients with medically refractory epilepsy not amenable to resection.

p112CAVERNOUS MALFORMATIONS SURGICAL EPI-LEPSY SERIESR. M. Buentello Garc�a*, C. Dom�nguez Rico*, D. San JuanOrta*, H. Sent�es Madrid�, E. Brust Mascher*, and M. A. AlonsoVanegas**Instituto Nacional de Neurolog�a y Neurocirug�a, DistritoFederal, Mexico; and �Instituto Nacional de Nutrici�n yCiencias M�dicas Salvador Zubir�n, Distrito Federal, Mexico

Purpose: To describe our surgical serie of patients presenting cavernousmalformations and intractable epilepsy.

Method: We retrospectively reviewed our series of 68 patients whounderwent complete lesion/epileptogenic zone resection, operated at theNational Institute of Neurology and Neurosurgery and the ABC MedicalCenter in Mexico City, from January 2005 to December 2011. Inclusioncriteria were: patients presenting with diagnosis of cavernous malforma-tion and intractable epilepsy. Presurgical evaluation was carried out uti-lizing a modified international protocol that included among others:complete medical history, MRI, surface EEG, Video-EEG, neuropsycho-logical testing and psychiatric evaluation, and in some selected casesfMRI.

Result: Mean age of seizure onset was 26.2 (SD € 12.3) years, 53.1%were men and 56.9% women, mean seizure frequency per month beforesurgery was 15.2 (SD € 29.6). Etiology: 92.6% of patients with singlecavernous malformation (29.4% extratemporal and 63.2% temporal

lobe), located 34.9% right and 65.1% left hemisphere; and 7.4% withmultiple cavernous malformations (3% only extratemporal and 4.4%temporal and extratemporal), 20% located on the right, 20% left and 60%both hemispheres. Surgical outcome: Engel I 88.2%, Engel II 7.3%. En-gel III 4.4%. Seizure frequency pre and post OP showed a statistical sig-nificance (p < 0.05). Mean follow up was 40.3 months. Morbilities: 4.4%quadrantanopsia, infection 1.5% and 0% mortality.

Conclusion: Complete surgical resection, included lesionectomy pluscorticectomy guided by electrocorticography demonstrates significantbeneficial results with total seizure control in the majority of cases. Elec-trical activity could be associated with dual pathology (cavernous malfor-mation plus cortical dysplasia).

p113PRE- AND POST-OP ACTIVATION OF THE MOTORCORTEX IN EPILEPSY WITH HEMIPARESIS AND RO-LANDIC ISCHEMIAR. F. Severino, D. Crestani, A. Palmini, J. Rubi¼o Hoefel,E. Paglioli, R. Nunes, and J. Costa Da CostaS�o Lucas Hospital, Porto Alegre, Brazil

Purpose: We want to study the role of the primary motor cortex (PMC)in patients with vascular destructive lesions in perirolandic regions. Neu-roplastic mechanisms operate and these patients have some motor func-tionality. This picture is more complex when occur seizures arousingfrom the scar and these area is resected. We report pre-and post-operativemotor functional magnetic resonance (fMRI) findings in 12 patients withrefractory epilepsy.

Method: Twelve patients with congenital hemiparesis underwent pre-surgical fMRI. All had cortical resections and were re-scanned 12 to 36months after surgery. Activation maps were superimposed over anatomi-cal images; analysis using Student t test with a P<0.0001. Limbs wereevaluated with neurological exam in 12 to 36 months.

Result: Pre-operatively, fMRI showed 3 main patterns. The first showedactivation of PMC adjacent to the destructive lesion. The second wascharacterized by absence of activation of the PMC ipsilateral to thelesion; and activation in the normal hemisphere. A third displayed bilat-eral activation of PMC. Postoperatively, patients who did not have acti-vation of the motor cortex adjacent to the lesion regained activation, andthat was accompanied by improved motor function.

Conclusion: These findings suggest that the PMC in the lesioned hemi-sphere may play a role in the motor function of the paretic limbs. Further-more, the post-operative activation of previously silent PMC in somepatients suggests that recurrent seizures and epileptogenic dischargesmay inhibit potentially preserved function. The improved motor functionaccompanied these positive fMRI changes adds credibility and raises theissue of new therapeutic.

p114ROLE OF NEURONAVIGATION DURING INVASIVEMONITORING FOR EPILEPSY SURGERYR. Vazquez, M. Caballero, P. M. Martinez, M. Rivero,J. Marquez, and M. D. JimenezUniversity Hospital Virgen del Rocio, Sevilla, Spain

Purpose: Invasive electrodes are used to localize the epileptogenic areain patients where structural lesions cannot be seen in imaging techniquesor the epileptogenic focus is not in the cerebral cortex and they are usedto map precisely the area where seizures arise.

Method: We present a case of a 13 years-old patient with daily com-plex-partial seizures refractory to medical treatment. Video-EEG showedleft temporal interictal epileptiform discharges and left theta temporalrhythm during ictal recording. Neuropsychological studies were normal.SPECT showed an area of hipoperfusion in mesial and anterior region of

34

Abstracts


the left temporal lobe. MRI showed a 1-cm left temporal subarachnoidcyst.

Result: Electrocorticography with subdural electrodes covering leftbasal frontal, left mesial temporal and left lateral temporal areas whereheld during four days. The accuracy of electrodes location was assuredby neuronavigation. Four seizures starting in left temporal mesial areawhere registered. A resection of the anterior left temporal pole was donewith very successful outcomes.

Conclusion: Neuronavigation with MRI allows us to plan before thecraniotomy the desirable location of the invasive electrodes. Invasiveelectrodes need to be placed exactly on the epileptic focus to avoidrecording spreading cortical discharges. In addition, neuronavigationallows us to double check the location of the invasive electrodes andquantify slight displacement before the surgical resection takes place.

p115TEMPORAL LOBE EPILEPSY SURGERY RESULTS OFAN EPILEPSY SURGERY UNIT WITH UP TO TENYEARS FOLLOW UPS. Gatzonis*, N. Georgakoulias�, A. Siatouni*, C. Tsekou*,T. Bouras*, E. Aggelopoulos*, M. Papathanassiou*,E. Aggelakis*, P. Patrikelis*, I. Kaskarellis*, E. Patsouris*, andD. Sakas**Athens Medical School, Athens, Greece; and �Athens GeneralHospital ‘‘G. Genimatas’’, Athens, Greece

Purpose: The surgical therapy of epilepsy is nowadays an establishedtherapy of drug resisting (dr) partial epilepsy especially for temporal lobeepilepsy (TLE). Surgical procedures for drTLE result in a curative effectwith no mortality and minimal serious side effects. We present the proto-col of the presurgical evaluation of patients with drTLE, the surgical pro-cedures and the results from a single center.

Method: 47 patients aged 15- 63 ys, 22 men and 25 women who wereproposed for surgical therapy for drTLE. 37 patients suffered from well-defined medial temporal lobe (MTLE) syndrome. Based on patients his-tory, interictal EEGs, long term video-EEG, Wada test and neuropsycho-logical evaluation they underwent surgery such as antero-medialtemporal lobectomy modified by Spencer or selective amygdalohippo-campal excision. Individualized procedures were performed in some ofthe other patients based on long term electrocorticography or/and intra-operative recordings.

Result: 64, 9% (24/37) of the patients with drug-resisting epilepsy of themesial temporal lobe are classified as Engel I after the surgical procedure.Nine patients show worthwhile seizures reduction (Engel II, III) and 2patients do not show any appreciable improvement (Engel IV). Twopatients did not present at the follow-up. The percentage of patients suf-fered from drTLE due to structural lesions who were proposed for surgi-cal therapy and remains seizure free is 60% (6/10). Serious permanentside effects: one patient remains with left hemiparesis.

Conclusion: Drug-resistant temporal lobe epilepsy is a syndrome with avery good response to surgical treatment. Our results are in concordancewith the literature.

p116HIGHER RESPONDER RATES TO VAGAL NERVESTIMULATION: IN SUPER-SELECTIVE PATIENTSS. Sinha, E. Khalid, F. Bamogaddam, M. Flatah, A. J. Sabbagh,and K. A. SiddiquiNational Neurosciences Institute, King Fahad Medical City,Riyadh, Saudi Arabia

Purpose: Vagal nerve stimulator (VNS) is a well recognized treatmentfor intractable epilepsy patients with upto 50% reduction in seizures. We

report results of VNS in our institute for its significance based on superselection of patient's types of seizures and responsiveness.

Method: We selected a cohort of 9 patients who underwent VNSimplantation (Cyberonics, Model 102 and 103) for intractable sei-zures who had comprehensive epilepsy evaluation using; long termEEG monitoring, dedicated structural and functional neuroimagingand neuropsychological evaluation. We studied their demographics,types of seizures, duration of epilepsy, seizure frequency pre andpost VNS insertion.

Result: We had 9 patients (5-males, 4-females) who underwent VNSsurgery over a period of 4 years with average (+SD) age 20.6 (€6.4)years. Duration of seizures before they underwent operation was 15.7(€6) years. Six patients had multi-focal epilepsy with secondary general-ization and three had primary generalized epilepsy. Average duration offollow up post VNS insertion was 18.4 (+11.3) months. Mean seizure fre-quency was 32.4 (range: 3–180) per month. Seizure frequency post sur-gery was 5.4 (range: 36–30) per month. All but 1 had >50% improvementin seizure frequency. 7 patients improved by >70% with 1 patient beingseizure free. There was no statistically significant correlation to the typeof seizure and response.

Conclusion: About >70% responder rates were seen in our cohortwhich is higher probably because of super-selection of patients aftercomprehensive epilepsy evaluation. VNS should be considered forpatients with intractable epilepsy who are not good candidates forepilepsy surgery.

p117SEIZURE REDUCTION AFTER DEEP BRAIN STIMULA-TION IN A PATIENT WITH PARKINSON DISEASEASSOCIATED WITH IDIOPATHIC GENERALIZED EPI-LEPSYT. Hoshida*, N. Maruyama*, Y. Sawai*, K. Kawata*,H. Hirabayashi*, K. Tamura�, and H. Nakase�

*National Hospital Organization, Nara Medical Center, Nara,Japan; and �Nara Medical University, Kashihara, Japan

Purpose: We report a case of seizure reduction after deep brain stimula-tion (DBS) of the subthalamic nuclei (STN) in a patient with idiopathicgeneralized epilepsy and Parkinson disease.

Method: A 61-year-old woman had experienced her first seizure at 10years of age. Generalized tonic-clonic seizures occurred during sleep.Her seizures occurred several times per year while she was taking 800mg valproate. She also started experiencing bradykinesia and limb tremorat 51 years of age. She was diagnosed with Parkinson disease andreceived medical treatment. She was finding it difficult to walk; as aresult, she was referred to the neurosurgery department for DBS surgeryat 54 years of age.

Result: Presurgical evaluation revealed no epileptic discharges duringlong-term electroencephalography monitoring. Valproate was discon-tinued and STN-DBS was performed uneventfully. Bradykinesia andbilateral tremor improved markedly after DBS. When the estimatedelectrical current was changed from 31.9 to 12.2 microampere at 5months after DBS, the first postoperative seizure occurred, and admin-istration of 400 mg valproate was restarted. One year later, when theestimated electrical current was changed from 29.3 to 15.6 microam-pere, the second and third postoperative seizures occurred. The esti-mated current was changed from 15.6 to 20.5 microampere and thepatient was administered 400 mg of valproate, after which she hasremained seizure free for 5.5 years.

Conclusion: Stimulation current conditions may be responsible forgeneralized seizure. The comorbidities of idiopathic generalized epi-lepsy and Parkinson disease showed improvement after STN-DBS.However appropriate stimulation conditions are required for seizurereduction.

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Abstracts



p118WHOLE EXOME SEQUENCING WITHIN AN IRISHPEDIGREE OF IDIOPATHIC GENERALISED EPILEPSYM. Mccormack*, G. D. O’Connor�, E. Heinzen�, K. V. Shianna�,J. Conroy§, S. Ennis§, D. Goldstein�, N. Delanty�, andG. L. Cavalleri**Royal College of Surgeons in Ireland, Dublin, Ireland; �

Beaumont Hospital, Dublin 9, Ireland; �Duke University,Durham, USA; and §University College Dublin, Dublin, Ireland

Purpose: Approximately 40,000 people in Ireland are diagnosed withepilepsy. Beaumont Hospital is the major tertiary referral centre for epi-lepsy in Ireland and through clinics we have recruited pedigrees withstrong familial patterns of seizures, providing a resource for identifyingcausal mutations in the Irish population.

Method: We present a large Irish pedigree containing 21 family mem-bers across three generations of which 8 individuals have a diagnosis orsuspected history of epilepsy, including absence seizures. We performedwhole exome sequencing on two siblings with idiopathic generalised epi-lepsy (IGE) and a third sibling with localisation-related epilepsy (LRE).

Result: From our analysis we limited candidate variants to those that areshared between affected individuals, functional and rare (<3% minorallele frequency in general population). Resulting candidate causal vari-ants included two novel non-synonymous SNPs in SLC2A1, a gene thatencodes the glucose transporter type 1 (GLUT1). Follow-up sequencingamong the extended pedigree showed near complete segregation with aseizure phenotype. Genotyping in a large combined cohort of sporadicepilepsy cases and population controls is currently ongoing to establishthe background frequency of these variants in the Irish population.

Conclusion: Through whole exome sequencing in just three individualswe have identified mutations in SLC2A1 as credible causal variants forIGE and/or LRE in an Irish pedigree. It remains to be seen if these spe-cific risk variants contribute to more sporadic forms of epilepsy. Thesefindings mirror recent discoveries which identified a defect in GLUT1 asa rare cause of IGE in patients with absence seizures.

p119PILOT STUDY FOR PCDH19 GENE TESTING IN BUL-GARIAP. Dimova*, A. Kirov�, A. Todorova�, T. Todorov�,B. Sukhudyan�, V. Bojinova*, and V. Mitev�

*St. Naum University Hospital of Neurology and Psychiatry,Sofia, Bulgaria; �Medical University, Sofia, Bulgaria; and�‘‘Arabkir’’ Joint Medical Center and Institute of Child andAdolescent Health, Yerevan, Armenia

Purpose: To report the results of the first genetic study for detection ofPCDH19 mutations in Bulgaria. Mutations in this gene cause the X-linked Epilepsy and Mental Retardation Limited to Females (EFMR),which is characterized by seizure onset in infancy or early childhood,cognitive impairment, and large phenotypic, including intrafamilial vari-ability. Usually, the PCDH19 mutations arise de novo, or are inherited bythe unaffected carrier fathers or by affected mothers.

Method: Whole PCDH19 gene sequencing was performed in 10 femalepatients with early onset epileptic encephalopathy.

Result: The molecular genetic study showed two novel PCDH19 muta-tions - c.2705dupA; p.Asp902Lysfs*6, and c.1091delC; p.Pro364Ar-gfs*4. In the first case, the healthy mother was a heterozygousasymptomatic carrier. The second mutation c.1091delC was de novo. In

both patients seizures started in infancy and occurred in clusters, mainlyprovoked by fever, but in the first one their frequency decreased withage, while in the second one a tendency to epileptic status was present.

Conclusion: Both cases confirm that seizures in clusters, initiallyprovoked by fever, are the most common epilepsy phenotype withinEFMR. Our first case is among the very few reported, where a het-erozygous female PCDH19 mutation carrier did not manifest anyclinical features. In our case totally skewed X-inactivation is a possi-bility that might explain the lack of clinical history in patient'smother, although it is not in correlation with previous study.Acknowledgments: The study was supported by Grant #49/2011,Medical University - Sofia, Bulgaria.

p120BORDERLINE DRAVET SYNDROME - BROADENINGTHE PHENOTYPIC SPECTRUM OF PYRIDOXINE-DEPENDENT EPILEPSYA. Baumgart*, M. Van Kempen�, N. Verhoeven�, R. StensbjerreMøller�, R. Boor§, H. Muhle*, J. Albers*, L. L. Klitten�,H. Hjalgrim�, D. Lindhout�, U. Stephani*, I. Helbig*, and S. VonSpiczak**University Medical Center Schleswig-Holstein, Kiel, Germany;�University Medical Centre Utrecht, Utrecht, The Netherlands;�Danish Epilepsy Centre, Dianalund, Denmark; and §NorthernGerman Epilepsy Centre, Schwentinental/Raisdorf, Germany

Purpose: Pyridoxine dependent epilepsy (PDE) and pyridoxal-5¢-phos-phate deficiency are rare autosomal recessive enzyme defects in vitaminB6 metabolism due to mutations in the ALDH7A1 and PNPO gene. Thephenotypic variability, however, is broad. The aim of this study was toasses the frequency of vitamin B6 deficiencies in unexplained infantileepilepsy.

Method: We screened 113 patients with unclear epilepsy syndromesstarting in the first year of life for mutations in ALDH7A1 and PNPO.Mutation analysis of the entire coding region of both genes includingadjacent splice sites was performed.

Result: No pathogenic mutations in PNPO were found. Sequence analy-sis of ALDH7A1 identified one patient as compound heterozygous forboth a novel, likely pathogenic c.1468A>G; p.Arg490Gly variant and aknown mutation c.1195G>C; p.Glu399Gln. The patient had a single neo-natal seizure on postnatal day 5. In the course of the disease, he presentedwith a Dravet-like phenotype including alternating hemiclonic seizures,prolonged seizures with febrile infections, theta rhythms and generalizeddischarges on the EEG and developmental delay plateauing from the ageof 2 years onwards. Partial response to antiepileptic drugs was observedas well as long seizure-free periods in adolescence. The patient neverreceived pyridoxine treatment and died at age 31 from epileptic statusprior to genetic diagnosis.

Conclusion: PDE should be considered in infants with severe epilep-sies including Dravet-like phenotypes. PDE may result in atypicalphenotypes mimicking well-defined epilepsy syndromes with partialresponse to anticonvulsive drugs and seizure-free periods without pyr-idoxine treatment.

p121PAEDIATRIC DIAGNOSIS NOT MADE UNTIL ADILT-HOOD: A CASE OF WOLF-HIRSCHHORN SYNDROMEA. Coppola*, V. K. Chintaphalli*, P. Hammond�, J. W. Sander�,and S. M. Sisodiya§

*Institute of Neurology, University College London, London,UK; �UCL Institute of Child Health, London, UK; �Heemstede,The Netherlands; and §UCL Institute of Neurology, London, UK

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Abstracts


Purpose: Wolf-Hirschhorn Syndrome (WHS) is a well-known syn-drome caused by 4p terminal deletion. The distinctive clinical features(facial dysmorphism, somatic defects, neurological impairment and sei-zures) typically lead to a genetic diagnosis early in life. Seizure onset istypically within the first year of life with febrile seizures, sometimesleading to status epilepticus. Seizures tend to improve/cease with age.We report on a person in whom the diagnosis was only made in adulthoodthrough array-CGH.

Method: The patient is aged 34 years. At 7 months she experienced atonic-clonic convulsion, at 10 months spasms, at 3 years convulsivestatus epilepticus and at 13 atonic seizures. At 23, she came under ourcare. Examination showed moderate learning disability and minor dys-morphisms, but no syndromic diagnosis was made despite three clini-cal genetics reviews. Her epilepsy has always been drug-resistant.Currently, she continues to experience 1–3 seizures/month, exacerbatedby high temperature. Genome-wide comparative genomic hybridizationand three-dimensional quantitative facial analysis have been per-formed.

Result: Array-CGH showed a 1.8 Mb 4p16.3 deletion. 3D quantitativefacial analysis classified her subtle facial dysmorphism as WHS-like.

Conclusion: This case highlights several issues: milder dysmorphicfeatures can be missed by clinical examination; quantitative facialanalysis can suggest diagnosis; array-CGH is an important diagnostictool in adults with drug-resistant epilepsy and additional features,even when clinical diagnoses have not been made; the phenotypicspectrum of even well-known syndromes may be broader than typi-cally appreciated.

p122DISTRIBUTION OF ELP4 POLYMORPHISMS IN RO-LANDIC EPILEPSY PATIENTS IN RELATION TO CLIN-ICAL PARAMETERSA. Gkampeta, L. Fidani, E. Pavlou, T. Katopodi, andF. Athanasiadou-PiperopoulouAristotle University of Thessaloniki, Thessaloniki, Greece

Purpose: Rolandic epilepsy (RE) is one of the most frequent epilep-tic syndromes in children. ELP4 is a component of the elongatorcomplex, involved in transcription and tRNA modification. The aimof this study was to investigate the possible effect of ELP4-Ear1and ELP4-BsrGI genotypes to specific clinical characteristics of chil-dren with RE.

Method: 31 children from northern Greece diagnosed with RE (agerange: 4–16 years) were genotyped for the ELP4-Ear1 and ELP4-BsrGIpolymorphisms. The polymorphisms were detected with a PCR-RFLPmethod, after designation of specific primers, PCR amplification andenzyme digest of the relevant fragment. The relationship of ELP4 poly-morphisms to clinical characteristics such as electroencephalographic(EEG) features, type of seizures and response to medication were ratedwith the Chi-square test of independence.

Result: ELP4-Ear1 polymorphisms (A/A, G/G, A/G) when comparedwith EEG features, type of seizures and response to medication did notshow any significant difference (P=0.681, P=0.359 and P=0.454 respec-tively). Similarly, neither ELP4-BsrGI polymorphisms (G/T, G/G, T/T)showed any significant difference (P=0.599, P=0.704 and P=0.787respectively).

Conclusion: The presence of ELP4-Ear1 G allele was associatedwith bilateral EEG features, while the ELP4-BsrGI G allele associ-ated with lateral EEG features and a better outcome with completecontrol of seizures for more than two years after seizure onset. Fur-ther studies in larger cohort of patients are needed in order to clarifythe effect of ELP4 genetic variations on clinical parameters in chil-dren with RE.

p123HIPPOCAMPAL SCLEROSIS WORSENS ADNFLE PHE-NOTYPE RELATED TO CHRNB2 MUTATIONA. Labate*, L. Mumoli*, A. Fratto*, A. Quattrone*, andA. Gambardella�

*University Magna Graecia Catanzaro, Catanzaro, Italy; and �

Institute of Neurological Sciences, Mangone (CS), Italy

Purpose: Autosomal dominant nocturnal frontal lobe epilepsy (ADN-FLE) is a distinct epileptic syndrome with a broad range of severity evenamong affected members of the same pedigree, and the level of pharmaco-resistance may reach 30%, close to that seen in sporadic focal epilepsies.

Method: To investigate this issue of phenotypic heterogeneity, we car-ried out a high-resolution MRI study in the ADNFLE family carrying theV287L mutation of the CHRN beta2 subunit (CHRNB2), which includesone pharmacoresistant patient. All 10 affected members were prospec-tively examined using a 3 Tesla MR750 GE MRI scanner with a 8-chan-nel head coil, based on a protocol routinely used at our clinic for patientswith epilepsy. MRI studies were evaluated in a manner blinded to theelectro-clinical data.

Result: The brain MRI was normal in all affected individuals except theright-handed 22 year-old girl (member III-7) with normal intellect, whohad refractory seizures and typical radiological signs of left hippocampalsclerosis (Hs). She had also had febrile seizures at age of 10 months.

Conclusion: The results of this study illustrate that Hs has offered a fer-tile substrate to develop intractable ADNFLE.

p124EUROEPINOMICS RES AR WORKING GROUP - ASHARED RESOURCE FOR THE IDENTIFICATION OFRISK FACTORS IN AUTOSOMAL RECESSIVE EPILEP-SIESA. Suls*, S. Weckhuysen*, P. De Jonghe*, andA. W. G. Euroepinomics Res Crp�

*VIB, Wilrijk, Belgium; and �http://bree.cs.nott.ac.uk/euroepinomics/index.php/projects-crps/res-main, Europe

Purpose: The aim of the autosomal recessive (AR) working group of theEuroEPINOMICS consortium on rare epilepsy syndromes (RES) is toelucidate the role of AR variants in epilepsies, as this is for the momentnot well documented.

Method: Within the consortium we collect all families that are or can becompatible with an AR mode of inheritance. We apply homozygositymapping in a subtype of families followed by whole exome sequencing(WES) and copy number variation analysis to identify causal variants.

Result: We ascertained within our consortium 23 consanguineous epi-lepsy families and 32 sibs with different types of epileptic encephalopa-thies (EE). Collection of additional families is an ongoing effort. Inconsanguineous families homozygous variants are most likely causingthe disease. By performing homozygosity mapping on one consanguine-ous epilepsy family we could identify a disease locus on chromosome 21(~9Mb). The analysis of the sequencing data of this locus is ongoing. Ifno homozygous variants/locus is identified in these families, othergenetic hypotheses will also be tested on the generated data. In sibs withEE several genetic hypotheses are tested: homozygous model, compoundheterozygous model and ‘‘de novo’’ mosaic autosomal dominant model.Analysis of WES data on the sib pairs is ongoing.

Conclusion: The large amount of families with different ethnical back-grounds compatible with an AR mode of inheritance we collected and thepreliminary genetic data we generated shows furthermore that recessivevariants are likely to cause some genetic epilepsies. Further genetic anal-yses will elucidate the proportion of AR inheritance in epilepsies.

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Abstracts


p125IDENTIFICATION OF A NOVEL GENE IN A FAMILYWITH SEVERE INFANTILE-ONSET EPILEPSYC. Depondt*, Y. Hitomi�, E. Heinzen�, S. Donatello*, H. Dahl�,S. Berkovic�, I. E. Scheffer�, B. Legros*, M. Pandolfo*,D. Goldstein�, and P. Van Bogaert**Universit� Libre de Bruxelles, Brussels, Belgium; �DukeUniversity, Durham, USA; and �University of Melbourne,Melbourne, Australia

Purpose: To describe the clinical characteristics, genetic analysis andfunctional studies in a family with autosomal recessive, infantile-onsetepilepsy and psychomotor retardation.

Method: We identified a family with 3/3 siblings with infantile-onsetepilepsy and psychomotor regression. Two siblings were exomesequenced. Shared homozygous, novel variants were sequenced in all 3siblings and their parents.

Result: Onset of focal seizures was between 19 and 35 months and psy-chomotor regression occurred soon after. Seizures were refractory tomedical treatment. Exome sequencing identified a homozygous missensevariant in the gene TNK2, encoding a brain-expressed tyrosine kinase.All 3 siblings were homozygous for the variant and both parents were het-erozygous. Genotyping of the variant in 3034 patients with epilepsy and1663 controls revealed no further homozygotes and very low frequenciesof heterozygotes (£0.002). Sequencing of all 15 exons and splice sites ofthe TNK2 gene in 110 patients with infantile-onset epilepsies, as well asanalysis of next-generation sequencing data in 131 cases with geneticgeneralized epilepsies and 297 controls showed no enrichment of puta-tive functional variants in cases compared to controls, although heterozy-gous truncating variants were overrepresented in patients with severeinfantile epilepsy. Functional studies demonstrated that the identifiedvariant abolishes NEDD4 binding to TNK2, preventing its degradationafter epidermal growth factor stimulation.

Conclusion: The combined results of our genetic and functional studiessuggest TNK2 as a novel gene for severe infantile-onset epilepsy. Defini-tive confirmation of pathogenicity will require identification in unrelatedpatients.

p126CLINICAL VARIABILITY RESULTING FROM THEMUTATIONS AT THE P.ARG1596 RESIDUE IN THESCN1A GENED. Hoffman-Zacharska, E. Szczepanik, R. Tataj, I. Terczynska,A. Goszczanska-Ciuchta, Z. Zalewska-Miszkura, D. Antczak-Marach, and J. BalInstitute of Mother and Child, Warsaw, Poland

Purpose: SCN1A, the gene encoding the sodium channel alpha 1 sub-unit, is one of the most important epilepsy genes. Mutation in SCN1A areassociated with various types of epilepsy. The clinical spectrum ofSCN1A mutations ranges from benign FS through spectrum of GEFS+ tosevere epilepsy syndromes such as Dravet Syndrome (DS) and intracta-ble childhood epilepsy with generalized tonic-clonic seizures (ICE-GTC). All identified SCN1A mutations are dominant and usually occurde novo, however familial cases also are described (5–10%). In the mostfamilies proband, shows the severe form of disease, while the remainingfamily members milder GEFS+ spectrum. We present unrelated DS/GEFS+ families, where disease is caused by missense mutations at resi-due p.Arg1596 of the Nav1.1 protein.

Method: Three unrelated multi-generations families with p.Arg1596missense mutations p.Arg1596His (2 families) and p.Arg1506Cys in theSCN1A gene were enrolled into the study. Mutations were identified bydirect sequencing of the SCN1A gene. Phenotypes of epilepsies wereclassified according to ILAE classification.

Result: The epilepsy phenotypes due to p.Arg1596 substitutions in allthree families fit to the spectrum of GEFS+. The epilepsy phenotypes dif-fer between probands and in mutation carriers range from asymptomatic,through FS, GEFS+ to borderline DS and focal seizures. In all families,we were able to analyse three generations and we observed the worseningof the symptoms in following generations.

Conclusion: The differences in clinical DS/GEFS+ picture resultingfrom the mutations of the same residue in the SCN1A gene may suggestinvolvement of genetic modifiers in final phenotype development.

p127PHENOTYPING DRUG RESPONSE IN EPILEPSYE. Caruana Galizia, K. Chinthapalli, J. Novy, J. W. Sander, andS. M. SisodiyaInstitute of Neurology, London, UK

Purpose: Little attention has been given to the spectrum of drugresponse in epilepsy. With a much recognized need for multicentre col-laborations, case definition will be key for appropriate case ascertain-ment. We propose definitions for different response groups in patientsexposed to levetiracetam and demonstrate the emergence of six differentresponse patterns.

Method: All data were collected retrospectively by accessing patientmedical. The following definitions were applied in order to classify theresponse pattern: the seizure-free group was defined as those cases thatachieved seizure freedom for a minimum of 12 months; partial respond-ers were defined as any case in which the number of seizures improvedby >25% from baseline; non-responders were defined as those cases withno more than a 25% fluctuation above or below baseline; seizure-worsen-ing was defined as >25% worsening of seizure frequency from baseline.

Result: Data were collected on 859 individuals and were distributedwithin the different response groups as follows: Seizure free group, 105cases; Partial responders, 147 cases; Non-responders, 92 cases; Seizureworsening, 82 cases. Response could not be classified in 242 cases. Twoother response patterns emerged: response before return to baseline (48cases) and response before worsening (45 cases).

Conclusion: We demonstrate that for the majority of cases the pattern ofdrug response can be classified into one of six different response-pheno-types. This work lays down the foundations for phenotyping of drugresponse in much needed multi-centre studies in epilepsy pharmacogenetics.

p128GLRB IS THE 3RD MAJOR GENE-OF-EFFECT INHYPEREKPLEXIAS. K. Chung*, C. A. Hunt*, A. V. Derrick*, T. D. Cushion�,S. E. Wood*, C. Drew*, O. W. Howells*, R. H. Thomas*, andM. I. Rees**Institute of Life Science, Swansea, UK; and �SwanseaUniversity, Swansea, UK

Purpose: Glycinergic neurotransmission is a major inhibitory influencein the central nervous system (CNS) and defects are primarily associatedwith paroxysmal neuromotor disorder, hyperekplexia or startle disease.The alpha1 subunit of the glycine receptor (GlyR) gene (GLRA1) and itscognate postsynaptic transporter (SLC6A5) are well-established genes-of-effect in hyperekplexia, nevertheless, up to 60% of hyperekplexiacases remain gene-negative. The beta subunit of the glycine receptor(GLRB), the heteropentameric partner subunit to GlyRa1, was selectedfor further analysis in gene-negative cases.

Method: 92 gene-negative hyperekplexia patients were selected for var-iation screening of the GLRB using multiplex PCR and direct Sangersequencing approach. All variants were excluded from normal controlsand mutation constructs were prepared for functional characterisation.

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Molecular modelling was also used to predict protein-damaging out-comes.

Result: This study identified 9 novel GLRB mutations within 8 indepen-dent hyperekplexia index-cases accounting for approximately 9% of thegene-negative cohort. This included 5 recessive, 2 dominant and 1 com-pound heterozygote inheritance scenarios, and were classified as 2 non-sense, 5 indels and 2 missense variants. The biological consequence ofthe nonsense and indel mutations was unambiguous and the 2 missensemutations were further investigated for electrophysiological analysis.

Conclusion: This study describes the largest genetic screening of GLRBin hyperekplexia and represents a 3rd major gene for hyperekplexia. It fur-ther implicates the glycinergic proteome as the basis for further analysis.

p129PHARMACOGENOMICS OF VALPORATE INDUCEDWEIGHT GAINJ. Chukwu*, S. Tirupathi�, M. King�, B. Lynch�, B. Mccoy§,D. Goldstein–, N. Delanty**, G. L. Cavalleri*, and D. Webb��

*Royal College of Surgeons in Ireland, Dublin, Ireland; �RoyalHospital Belfast, Belfast, UK; �Children's University Hospital,Dublin, Ireland; §Our Lady's children's Hospital Crumlin,Dublin, Ireland; –Duke University Institute for Genome Sciencesand Policy, Durham, NC, USA; **Beaumont Hospital, Dublin,Ireland; and ��Adelaide & Meath Hospital IncorporatingNational Children's Hospital Dublin, Dublin, Ireland

Purpose: Sodium valproate (VPA) is one of the most commonly usedAEDs in the treatment of partial and generalised seizure disorders.Weight gain is one of the known side effects of VPA. It has been esti-mated that between 10 and 70% of people exposed to VPA experiencesome weight gain. About 10% of these patients have significant weightgain (> 10% of pre-VPA initiation weight) necessitating discontinuationof therapy.

The exact mechanism of weight gain in VPA is not fully understood.This study seeks to test the hypothesis that individuals with commongenetic variants associated with obesity are more prone to developingVPA-induced weight gain than those who do not. This will be explored ina paediatric cohort diagnosed with epilepsy and take VPA as antiepilepticdrug.

Method: Retrospective study looking at clinical phenotype of paediatricepilepsy patients in Dublin. Phenotypic data will be utilised in correlatingthe results with genome wide association analysis on patient DNA samples.

Result: 152 patients have been recruited to the study to date. It is hopedthat by December 2012, 250 individuals would have been recruited.

Conclusion: Using the latest technology in the study of human genomeit is hoped that the genomic factors responsible for the weight change inchildren with epilepsy taking valproic acid will be determined.


p130DOES THE BDNF VAL66MET POLYMORPHISMINFLUENCE COGNITIVE FUNCTION IN PATIENTSWITH MTLE?J. Stretton, A. Foulkes, P. J. Thompson, S. Baxendale,M. K. Sidhu, E. Williams, J. Burdett, S. M. Sisodiya, J. Duncan,and M. MatarinUCL, London, UK

Purpose: The Val66Met (rs6265) polymorphism in the brain-derivedneurotrophic factor gene (BDNF) has been associated with cognitive per-formance as well as structural and functional hippocampal differences, inhealthy controls and some clinical populations. Deregulation of BDNFexpression has also been implicated in the mechanisms underlying epile-ptogenesis.

Mesial temporal lobe epilepsy (mTLE) is the most common partialepilepsy in adults who medically refractory. Patients with mTLE usuallypresent cognitive dysfunction with memory impairment as a prominentcognitive deficit. Approximately one third of patients also experiencesignificant post-operative memory decline and transient language dys-function following epilepsy surgery.

Method: We investigated the association of Val66Met polymorphismwith the results of cognitive tests (n=282), hippocampus volume (n=108)and fMRI data (n=47) during memory-encoding and language paradigmsin a group of patients with mTLE.

Result: Independently of the age, gender and seizure laterality (right orleft) the patients with mTLE and carriers of met allele (n=83) had signifi-cantly lower scores in delayed memory tasks and were significantly morelikely to display post-operative decline in measures of both verbal andvisual memory than Val homozygotes patients (n=199).

There was no significant effect of the genotype on immediate memory,fluency or hippocampus volume. fMRI activation during memory encod-ing and verbal fluency revealed the Met allele carriers had significantlyreduced default mode network activation compared to Val/Val carriers.

Conclusion: These results suggest the BDNF Val66Met polymorphismmay contribute to memory function in patients with mTLE and mayinfluence the responsiveness of the default mode network.

p131A COMPOUND HETEROZYGOUS MISSENSE MUTA-TION AND A LARGE DELETION IN THE KCTD7 GENEPRESENTING AS AN OPSOCLONUS-MYOCLONUSATAXIA–LIKE SYNDROMEL. Blumkin*, S. Kivity�, D. Lev�, E. Leshinsky-Silver�, andT. Lerman-Sagie�

*Holon, Israel; and �Wolfson Medical Center, Holon, Israel

Purpose: To describe a new presentation of KCTD7 mutation: an opso-clonus-myoclonus ataxia like syndrome with subsequent development ofgeneralized continuous epileptic activity without clinical correlation, andpartial clinical response to steroid therapy.

Method: We recorded the clinical course of the disease, the evaluationand the response to steroid therapy. The patient is a five-year-old boywho was diagnosed as having opsoclonus-myoclonus ataxia syndrome atthe age of 16 months and was therefore treated by an OMS protocolincluding high dose ACTH, and later dexamethasone. After the appear-ance of continuous epileptic activity on recurrent video -electroencepha-lographic studies at the age of 3 and a half year a neurodegenerativedisorder was suspected. After excluding possible genetic causes, wholegenome exome sequencing was performed in order to identify the causa-tive gene. Sequence variants were filtered according to the phenotype.Sanger sequencing was performed to confirm the point mutation andMLPA was used for screening for a possible deletion in the second allele.

Result: Two pathological variants were found in the KCTD7 gene:R84W and a large deletion of exons 3 and 4. The father is heterozygousfor the R84W mutation and the mother is heterozygous for the exon 3+4deletion.

Conclusion: KCTD7 mutations were described in a single family withprogressive myoclonus epilepsy. Our patient presented with non epilepticmyoclonus, ataxia and opsoclonus responsive to corticosteroid treatmentand only two years later developed an epileptic EEG witout overt sei-zures. The different phenotype broadens the spectrum of KCTD7 relateddiseases.

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p132SUDEP AND FAMILIAL EPILEPSYR. H. Thomas*, W. O. Pickrell*, A. J. Johnston*, C. Hammond�,C. Drew*, P. Smith�, and M. I. Rees§

*Wales Epilepsy Research Network, Swansea, UK; �Guy's and StThomas’ NHS Foundation Trust, London; �University Hospitalof Wales, Cardiff; and §Swansea University, Swansea, UK

Purpose: The Wales Epilepsy Research Network has been continuallyrecruiting epilepsy families since 2006 into genetic studies. The causes ofsudden unexpected death in epilepsy (SUDEP) are yet to be fully deter-mined but amongst competing theories are genetic causes of cardiac orrespiratory failure.

Method: The first eighty families recruited into our study were availablefor analysis. The consensus definition for SUDEP was used to identifycases (Nashef 2011) and project records and clinical notes were scrutin-ised for clinical characteristics.

Result: Sixteen of the eighty families had a probable or definite SUDEPcase; no family had two SUDEP deaths. Not one of these occurred fol-lowing recruitment (and so we have no DNA for analysis) and there wereno clear clinical patterns to be identified from the familial epilepsy diag-nosis. It was common for the sibling of the person who had a SUDEP tobe the affected index case.

Conclusion: We are unable to conclude that familial epilepsy is a pro-ven risk for SUDEP. Rather we propose that families with epilepsy thathave had a SUDEP death are strongly motivated to participate in researchand that investigators should not be deterred from involving them ingenetic research.

p133FAMILIAL MOVEMENT-INDUCED REFLEX EPILEPSY(FMIRE): A NOVEL GENETIC EPILEPSY SYNDROMEWITH POSSIBLE MAPPING TO CHROMOSOME 1PS. Schirwani, and D. CromptonInstitute of Genetic Medicine/Newcastle University, Newcastleupon Tyne, UK

Purpose: 1. To evaluate relative merits of various linkage and homozy-gosity mapping tools in a small UK family with a novel movement-induced reflex epilepsy in two siblings. Repetitive voluntary movementof any body part evokes voluntary clonus in that body part, clonus eithersubsided within seconds or culminates in generalized tonic-clonic sei-zures. 2. Attempt to identify the causative gene.

Method: Various linkage analysis and homozygosity mapping methodswere evaluated then applied to genome wide SNP data from the FMIREfamily. Copy number variant (CNV) analysis was also performed. Candi-date genes were selected from the homozygous region. The most likelycandidate gene was sequenced.

Result: A 2.0 Mb homozygous region was identified on chromosome 1.This region was homozygous in the affected sib-pair but not in the unaf-fected sibling or parents. KIF17, which is a brain specific motor proteininvolved in transporting ion channels, was identified as the most likelycandidate gene.

Sequencing KIF17 gene revealed many variants, though non ofthese were likely to be pathological. No pathological CNV wasfound, this result therefore did not contradict the homozygous modelfor FMIRE. Parametric linkage analysis using a recessive model didnot show linkage signals. This result was expected due to small sizeof FMIRE family.

Conclusion: 1. In Familial movement-induced reflex epilepsy voluntarymovement induces focal clonus, then generalised tonic-clonic seizures.2. Recessive inheritance is likely. 3. Homozygosity mapping identified apromising homozygous region on chromosome 1. 4. No pathogenic

mutations were identified in the KIF17. 5. The mutation probably lieselsewhere in the identified homozygous region.

p134STXBP1 MUTATIONS AS A CAUSE OF DRAVET SYN-DROMES. Weckhuysen*, P. Holmgren*, A. Suls*, R. Hendrickx*,R. Steensjberre Møller�, H. Hjalmgrim�, G. Carvill§,H. Mefford§, I. E. Scheffer–, and P. De Jonghe**University of Antwerp, VIB Department of Molecular Genetics,Antwerp, Belgium; �Danish Epilepsy Centre, Dianalund,Denmark; �Instute for Regional Health Services, University ofSouthern Denmark, Odense, Denmark; §University ofWashington, Division of Genetic Medicine, Seattle, USA; and–7Florey Neurosciences Institutes, Austin Health, Melbourne,Australia

Purpose: STXBP1 mutations have been described in Ohtahara syn-drome, West syndrome and in patients with an unclassified early onsetepileptic encephalopathy. Although a phenotypic spectrum of STXBP1encephalopathy is emerging, further delineation of the spectrum is stillneeded. Furthermore, the genetic cause for 20% of Dravet patients is stillunknown. With this study we aimed to identify additional genes for Dra-vet syndrome, and to specify whether STXBP1 mutations are present inthis severe epilepsy syndrome.

Method: We combined two complementary strategies: STXBP1 screen-ing was performed in a wide range of severe epilepsies including 22patients with Dravet syndrome. Additionally whole exome sequencing(WES) was performed on a cohort of SCN1A negative Dravet patientsand their parents. Findings were confirmed by classical Sanger sequenc-ing.

Result: We detected 2 de novo missense mutations in 2 patients withDravet syndrome. c.1334A>C was detected by direct Sanger sequencingof STXBP1 and c.847G>A by WES. Seizure onset was at 6 and 11months respectively. Both patients had febrile seizures and multiple afe-brile seizure types. EEG showed multifocal epileptiform activity in bothpatients. Development slowed down after epilepsy onset in both patients,although in the first patient some delay was noticed already at the age of3 months. At age 19 years he is severely mentally disabled and wheelchair bound. The second patient has a normal neurological exam.

Conclusion: STXPB1 mutations are a rare cause of Dravet syndrome.Screening of STXBP1 in larger cohorts of SCN1A negative Dravet is cur-rently ongoing.

p135DENSE SURFACE MODELS OF FACE SHAPE ASSIST INPREDICTING PATHOGENIC COPY NUMBER VARI-ANTSK. Chinthapalli*, E. Bartolini*, J. Novy*, M. Suttie�, C. Marini�,M. Falchi�, Z. Fox§, L. Clayton*, J. W. Sander*, R. Guerrini�,C. Depondt–, R. Hennekam**, P. Hammond�, andS. M. Sisodiya**UCL Institute of Neurology, London, UK; �UCL Institute ofChild Health, London, UK; �Children's Hospital Meyer,Florence, Italy; §UCL, London, UK; –Universit� Libre deBruxelles, Brussels, Belgium; and **University of Amsterdam,Amsterdam, The Netherlands

Purpose: Copy number variants (CNVs) are increasingly recognised asgenetic contributors to epilepsy. Pathogenic CNVs can manifest as a

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range of phenotypes, such as intellectual disability, autism, partial or gen-eralised epilepsy syndromes, and are important to detect. Facial dysmor-phism also arises from CNVs and we show that people with epilepsyrelated to CNVs have a more atypical face shape. Furthermore, in peoplewith epilepsy, face shape analysis is shown to successfully predict thosecarrying pathogenic CNVs.

Method: Stereophotogrammetry was used to capture 3D face surfaceimages of 181 patients with epilepsy and 336 control subjects. Allpatients underwent molecular analysis to determine the occurrence ofCNVs. Images of 118 patients and all controls were used to build densesurface models for the face, periorbital region and perinasal region. Wethen quantified a measurement of face shape difference (FSD) for faceregions and determined correlation of FSD with occurrence of CNVs.Predictive accuracy of the correlation was tested unseen on a secondgroup of 63 patients.

Result: FSD predicted presence of a pathogenic CNV in 63 new patientswith high sensitivity (80%) and specificity (78%). Within all 181patients, 43 had pathogenic CNVs and significantly more atypical perior-bital (Mann-Whitney test; p<0.001), perinasal (p<0.001) and facial(p<0.001) shapes. These differences were not explained by age, ethnicity,anti-epileptic drug use or facial injury.

Conclusion: In people with epilepsy, stereophotogrammetry and faceshape analysis can successfully and objectively assist in identifying thosewith pathogenic CNVs. This can lead to earlier diagnosis and improvedmanagement of their epilepsy.

p136ALICE IN WONDERLAND SYNDROME: EPILEPSY,MIGRAINE OR BOTH?W. O. Pickrell*, R. H. Thomas�, A. J. Johnston�, C. White�, andM. I. Rees�

*Institute of Life Sciences, Swansea, UK; �Wales EpilepsyResearch Network, Swansea, UK; and �Morriston Hospital,Swansea, UK

Purpose: We present a family where 10 members of the pedigree suf-fer distinct, stereotyped episodes of hyper and hyposchematia, meta-morphopsia including teleopsia and pelopsia and altered timeawareness consistent with the Alice in Wonderland Syndrome (AIWS).Descriptions of the episodes include sensations of time slowing andspeeding, sensations of hand and jaw enlargement and feelings ofbeing detached from reality. Amongst the 10 affected family members,4 also have epilepsy, 1 also has migraine and 3 people only haveAIWS.

Method: We conducted an study of AIWS incidences in epilepsy andmigraine to assess its potential as a synergistic feature bridging both phe-notypes (if not more).

Result: Since the first published description of AIWS in 1955, therehave been several reports describing associations with migraine, epi-lepsy, viral Illnesses (Epstein Barr Virus and H1N1) and also drugsincluding topiramate and dihydrocodeine. The fact that AIWS can occurwith or without migraine or typical epileptic seizures raises the questionas to its exact nature – is it a form of migraine, epilepsy, both (migra-lepsy) or neither?

Conclusion: There is phenotypic overlap between migraine and epi-lepsy and presentation of AIWS: Mutations in genes encoding ion chan-nels have recently been associated with both migraine and epilepsy. Theabnormally high incidence of AIWS, migraine and epilepsy in this familymeans there is a underlying genetic cause which we are currently investi-gating. A biological model for the pathogenesis of AIWS could help fur-ther our understanding of both migraine and epilepsy - the two mostcommon paroxysmal brain disorders.

p137EFFECT OF UGT1A6*2 GENETIC POLYMORPHISMON THE DOSES, PLASMA CONCENTRATION ANDMETABOLISM OF VALPROIC ACID IN PATIENTSWITH EPILEPSY FROM R.MACEDONIAZ. Sterjev*, G. A. Kiteva-Trencevska�, J. T. Ribarska*,E. Cvetkovska�, I. Kuzmanovski�, I. Petrov�, A. K. Nestorovska*,N. Matevska*, Z. Naumoska*, A. Dimovski*, and L. Suturkova**Faculty of Pharmacy, Skopje, Macedonia; and �UniversityClinic of Neurology, Skopje, Macedonia

Purpose: The GG genotype of UGTIA6 A541G polymorphism has beenassociated with high enzyme activity compared to the wild type AAgenotype. The aim of our study was to investigate the distribution and fre-quency of UGTIA6*2 genotype in epileptic patients (113 VPA respond-ers/40 VPA resistant patients) and to evaluate the effects of thispolymorphisms on maintenance doses, plasma concentrations and metab-olism of VPA.

Method: TaqMan assay-real time PCR, fluorescence polarizationimmunoassay and HPLC method.

Result: No statistically significant difference in the allelic frequencyand genotype distribution (0.49, 0.35, and 0.15, and 0.32, 0.52 and 0.15for AA, AG and GG genotypes, p=0.46) was determined between VPAresponders and VPA resistant patients, respectively. The mean values ofdaily maintenance doses of VPA in patients with AA, AG and GG were:883mg+/)350.4, 977.5mg+/)359.1 and 961.7mg+/)346.6, respectively.The values of total plasma levels corresponding to the genotypes were367.5 € 133.5 lmol/L for AA, 380.2+/)111.2 lmol/L for AG and353.6+/)122.5 lmol/L for GG genotype. The differences in doses andplasma concentrations were not statistically significant (KW test H=2.45p=0.29 and ANOVA F=0.28 p=0.76). Patients with GG genotype wereassociated with higher value for Ke compared to patients with AA geno-type (0.04h-1 +/) 0.01 vs 0.03h-1 +/) 0.01, respectively). Patients withGG genotype had lower values for E1/2, AUC, Mean Residence TimeMRT, Cmax and Tmax of VPA.

Conclusion: Our data suggest that patients with GG genotype for UG-TIA6 A541G polymorphisms are associated with higher maintenancedaily doses of VPA, lower plasma concentrations and faster eliminationof this antiepileptic drug.

p138PHARMACOGENOMIC TESTING-BASED PERSONAL-IZED MEDICINE FOR EPILEPSY. ANALYSIS OF 10CONSECUTIVE REFRACTORY EPILEPTIC PATIENTSP. E. Bermejo, A. Fraile, J. Chamorro, and E. BlancoFundaci�n San Jose, Madrid, Spain

Purpose: Although 30% of all epileptic patients are resistant to antiepi-leptic drugs (AEDs), currently a trial-and-error approach is employed todetermine the most effective AED and dosage for a patient. Pharmacoge-netic testing for variations in the genes encoding drug-metabolizingenzymes and drug transporters has been proposed as a personalized medi-cine for these patients. The aim of this study is to describe our experiencein 10 consecutive refractory epileptic patients.

Method: Ten mentally retarded and refractory epileptic patients wereenrolled in this study. A genetic test (Neurofarmagen� epilepsy) formeasurement of 11 genetic variations of single nucleotide polymor-phisms was performed. Number of pharmacogenetic variations, AEDsaffected for these pharmacogenetic variations, antiepileptic therapy mod-ifications, clinical improvement of the patients and decrease of seizureswere collected and analyzed.

Result: All enrolled patients displayed pharmacogenetic variations(3.8€0.8) and all of them showed affected AEDs (7.8€4.2). Most

41

Abstracts


frequently involved genes were ACBC1, SCN1A and EPHX1. Accordingto these results, antiepileptic therapy was modified in 7 patients (70%)including AEDs changes and their dosages. A clinical improvement wasachieved in 5 patients (50%): 3 of them obtained a better control of theirepilepsy while 2 of them achieved a better side effects profile.

Conclusion: Personalized medicine for epilepsy based on pharmacoge-nomic testing is a new avenue for optimizing AED therapy. According toour results, some refractory epileptic patients may benefit from pharma-cogenetic testing for variations in the genes encoding drug-metabolizingenzymes and drug transporters of AEDs. More studies are warranted toconfirm these results.

p139EXPANDING THE ROLE OF COPY NUMBER VARIA-TION IN EPILEPSY PATHOLOGYL. Addis, D. A. Collier, and D. K. PalInstitute of Psychiatry, King's College London, London, UK

Purpose: Copy Number Variation (CNV) has a well-documented asso-ciation with epilepsy. We seek to expand the genotype-phenotype rela-tionships between epilepsy and other neurodevelopmental disorders withCNV using the clinical genetics database, Brain and Body GeneticResource Exchange (BB-GRE).

Method: 10,397 individuals referred for cytogenetic investigation wereanalysed for CNV using a customized 44K Agilent comparative genomichybridization (aCGH) array. aCGH results were entered into BB-GRE.We searched BB-GRE for the phenotype ‘epilepsy’ or ‘seizure’. Caseswere compared with controls in DECIPHER and DGV databases.

Result: We identified 186 patients with epilepsy or seizures. 63% ofthese patients also had developmental delay or intellectual disability.30% reported ADHD, speech/language problems or autism. We found 23patients with large CNVs at known neurocognitive disorder hotspots;16p11.2 (n=8), 15q13.3 (n=6), 22q11.21 (n=4), 16p13.11 (n=3), 1q21.1(n=2). Another patient had a large novel deletion of 11.7Mb on 1p36.Several patients had disruptions of known epilepsy genes: a double dele-tion of only CNTNAP2 (n=1) a deletion of KCNQ2 and CHRNA4 (n=1),duplications of both CDKL5/STK9 and MECP2 on ChrX (2 male). Sev-eral patients harboured novel microdeletions or duplications.

Conclusion: Our large clinical genetics database confirms and expandsthe role of CNV in the pathology of the epilepsies, especially the comor-bidity with neurodevelopmental disorders. Identified CNVs frequentlyoccurred in known hotspots or epilepsy genes. Rare or de-novo CNVscontaining potentially pathogenic gene aberrations will be investigatedfurther. The BB-GRE database and the clinical genetics service areimportant to drive genotype-based diagnoses and the delineation of‘‘genomic syndromes’’.

p140IDENTIFYING GENES INVOLVED IN EPILEPTICENCEPHALOPATHY BY WHOLE EXOME SEQUENC-ING IN FAMILIESE. H. Brilstra, R. Van ‘T Slot, S. Van Lieshout, B. Koeleman, andC. G. F. De KovelUMC Utrecht, Utrecht, The Netherlands

Purpose: Epileptic encephalopathies are characterized by slowing orregression of development that is attributed to epileptiform activity.When no external cause is prevalent, the condition is assumed to begenetic. In some families, multiple sibs are affected. A few genetic causesfor epileptic encephalopathy are known, but many cases cannot beexplained. Probably, there is high genetic heterogeneity. We aim to iden-tify new genes as causes for these encephalopathies.

Method: We have collected patients with healthy parents. Five familieshad multiple affected sibs, ten patients had no affected relatives. We

assumed a recessive model, either homozygous or compound heterozy-gous in the multiplex families, while in the sporadic cases a de novomutation is an additional possibility. Whole exome sequencing was per-formed to identify candidate mutations.

Result: So far, we have identified mutations in X-linked genes CDK16and GABRE as possible candidates in male patients. Further analysis ofthe remaining families may identify more candidate mutations. To con-firm their pathogenicity, we will combine our results with those of otherresearch groups.

Conclusion: Whole exome sequencing can be used to identify geneticcauses for monogenic disease when performed in families.

p141PRELIMINARY DATA ON THE USE OF MTOR INHIBI-TORS FOR MANAGEMENT OF REFRACTORY SEI-ZURES AND FOR THE MANAGEMENT OFSUBEPENDYMAL GIANT CELL ASTROCYTOMAS INPATIENTS WITH TUBEROUS SCLEROSIS COMPLEXM. Cardamone, D. Flanagan, D. Mowat, S. Kennedy,M. Chopra, and J. A. LawsonUniversity of New South Wales, Sydney, NSW, Australia

Purpose: Background: Tuberous sclerosis complex (TSC) is a geneticdisorder involving the mammalian target of rapamycin (mTOR) secondmessenger pathway. This results in non-malignant tumours such as sub-ependymal giant cell astrocytomas (SEGAs) and also complex pathwaysleading to intractable epilepsy. Aim: To evaluate the efficacy and sideeffects of mTOR inhibitors in patients with TSC and intractable epilepsyand or SEGA.

Method: A retrospective single centre series of 5 patients with TSC andrefractory seizures treated with Rapamycin. An additional 7 patients withTSC and SEGA who received Rapamycin (R) or Everolimus (E), bothmTOR inhibitors for non-surgical management between 2010 and 2012.Medical records and MRI brain imaging were reviewed to assess seizurecontrol, side effects, and surveillance performed. SEGA volumes wereassessed longitudinally using 1.5T MRI and using the Analyze software.

Result: Seizure efficacy: One participant experienced seizure freedomand another experienced >90% seizure reduction. Another experienced a>50% seizure reduction. Three patients reported subjective improvedlearning. SEGA reduction: By three months of treatment there is statisti-cally significant reduction in the SEGA volumes in at least 2 patientswho received mTOR inhibitors (p<0.006). All seven patients had reduc-tions of SEGA at 6 months by 37–65% Side effects: Aseptic meningitisrequiring hospitalisation (1 patient), dyslipidaemia (3 patients), and anor-exia (1 patient).

Conclusion: Preliminary data suggests mTOR inhibitors may be usefulfor controlling seizures in patients with TSC who are refractory to anti-convulsants and for reducing the volume of SEGAs in patients with TSC.Only one patient had a significant adverse event (aseptic meningitis).


p142IDENTIFICATION OF A NOVEL GENETIC LOCUS FORFEBRILE SEIZURES IN A MALTESE FAMILYC. Farrugia*, M. Cassar�, and J. Mifsud**University of Malta, Msida, Malta; and �MLSBioDNA, Paola,Malta

Purpose: The aim of this study was to narrow down a previously identi-fied region of about 20cM on chromosome 20 linked to familial febrile

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Abstracts


seizures (FEB) by performing another linkage study using short tandemrepeat (STR) markers.

Method: The study was carried out on a Maltese three generation familyhaving seven members with a phenotype compatible with FEB. A total ofseven STR markers, from D20S1085 until the end of the telomere, at anaverage spacing of 2cM were genotyped in the thirteen family membersusing fluorescent methods. Following genotyping, multipoint parametricand non-parametric linkage analysis were performed. Penetrance wasgiven to be 0.9.

Result: The previously identified linkage region was confirmed andreduced to approximately 5cM on cytogenic band 20q13.3. Assumingautosomal dominant inheritance with incomplete penetrance, the highestlogarithm of the odds score was 2.67 (p

Conclusion: This study has identified a novel locus of interest associ-ated with the FEB phenotype in a Maltese family, thus contributing to abetter understanding of the syndrome and adding to the growing knowl-edge of the genetics of such complex diseases.

p143CHROMOSOMOPATHIES AND EPILEPSYJ. P. Domingos, F. Correia, and J. ChavesHospital de Santo Ant�nio, Centro Hospitalar do Porto, Porto,Portugal

Purpose: Chromosomopathies may originate CNS malformations, asso-ciated with cognitive impairment. Although being a rare cause, they con-stitute a risk factor for epilepsy. They are typically related to certaintypes of epilepsy.

Method: We present 9 patients with chromosomopathy and epilepsyfollowed in our outpatient clinic.

Result: 1 – 58 year-old woman, Trisomy 21, generalized epilepsy withgeneralized tonic-clonic seizures (GTCS) controlled with valproic acid(VPA) 500+500mg/day. 2 – 56 year-old woman, Trisomy 21, senile myo-clonic epilepsy, not controlled with levetiracetam 1000+500mg/day. 3 –9 year-old boy, free Trisomy 21, generalized epilepsy with GTCS, con-trolled with VPA 200+200mg/day. 4 – 45 year-old man, Klinefelter syn-drome, generalized epilepsy with GTCS controlled with VPA500+1000mg/day. 5 -20 years-old man, fragile X syndrome, generalizedepilepsy with GTCS, controlled with VPA 200+200mg/day. 6 – 37 year-old woman, 3p25 Deletion, juvenile absence epilepsy controlled withVPA 500+500mg/day. 7 – 31 year-old woman, trisomy 15, probablysymptomatic focal epilepsy with subependymal heterotopia controlledwith topiramate 50mg/day. 8 – 22 year-old woman, ring chromosome 20syndrome, severe symptomatic encephalopathy with febrile seizures andrecently GTCS under VPA (2ml+2ml/day). 9 - 19 year-old man, fragileX syndrome, neonatal seizures, sensory seizures, controlled with ox-carbazepine 600+600 mg/day.

Conclusion: Trisomy 21 was the most frequent cromosomopathy found.These patients have a bimodal distribution: in those starting after 50 year-old an association with GTCS and senile myoclonic epilepsy is described.Deletion 3p25 is usually associated with febrile seizures and develop-mental delay, unlike our patient. The association between chromosome15 and subependymal heterotopia is not described.

p144TARGETED NEXT GENERATION SEQUENCING ASDIAGNOSTIC TOOL IN EPILEPTIC DISORDERSJ. Lemke*, E. Riesch�, T. Dorn�, Y. Weber§, H. Lerche§,D. Bçhm�, and S. Biskup�

*University Children's Hospital, Bern, Switzerland; �CeGaTGmbH, T�bingen, Germany; �Swiss Epilepsy Center, Z�rich,Switzerland; and §University of T�bingen, T�bingen, Germany

Purpose: The epilepsies are a very heterogeneous group of commonneurological disorders comprising many individually rare diseases. Thus,genetic diagnosis oft remains difficult. With our approach we aim toreveal the genetic basis of epileptic disorders in so far unresolved cases.

Method: We enriched a panel of 323 epilepsy-associated genes using acustom designed Agilent SureSelect in solution kit and sequenced on aSOLiD 4 platform.

Result: We screened >50 unknown cases with a broad spectrum of epi-lepsy phenotypes. We detected causative aberrations in commonlymutated ion channel genes (e.g. SCN1A, SCN2A) as well as in rarelyaffected genes (e.g. STXBP1, MFSD8). Surprisingly, we detected manymutations in extremely uncommon genes (e.g. KCTD7, ARHGEF9,KCNJ10, SMS). We also revealed SCN1A mutations in three patientswhere conventional testing (Sanger sequencing/HRM) failed to detectthe mutations.

Conclusion: We have successfully established a fast and cost efficientgenetic screening method for patients with seizure disorders. We wereable to uncover the genetic basis of many so far unresolved cases withepilepsy. We detected mutations in patients with both clear and unspe-cific epilepsy phenotypes. We revealed false negatives in conventionalgenetic testing methods. Many mutations were detected in genes that onlyin very rare instances have been associated with epileptic disorders. Thus,many rare epilepsy disorders might perhaps be more common but simplyunderdiagnosed due to unspecific and diffuse phenotypes. Therefore, ourapproach may contribute in collecting information on both well-knownand unacquainted epilepsy disorders and in revealing their true pheno-typic spectrum.

p145EARLY EPILEPTIC ENCEPHALOPATY: A PECULIARGENETIC CASEP. Guimar¼es*, M. Santos*, R. Chor¼o*, J. S��, and I. Carrilho**Centro Hospitalar do Porto - Hospital Maria Pia, Oporto,Portugal; and �Hospital Pedi�trico do Centro Hospitalar deCoimbra, Coimbra, Portugal

Purpose: To present the case of a child with a deletion in the STXBP1gene with a peculiar electroclinical presentation and good outcome.

Method: Case Report.

Result: We describe a five years-old girl, with development marked bycognitive delay and early-onset epilepsy. Seizures started in the neonatalperiod predominantly with sleep related episodes that occurred in clus-ters, and with pleomorphic phenomenology evolution until the present:first focal seizures with automatisms and right hemiconvulsions, laterepileptic spasms and finally seizures with right eyes deviation and fen-cer's posture. The general examination was normal, with no dysmorphicfeatures, and neurological evaluation only detected cognitive handicap.The sequential electroencephalografic analysis showed distinct ictal andinterictal patterns: initially localized to the anterocentral bilateral regionswith burst-suppression pattern, later on both anterolateral regions withsubsequent progression to a predominantly bilateral posterior epilepti-forme activity, and finally lateralized to the anterior left region. Investi-gation excluded metabolic and exclusively structural brain diseases, butfunctional imaging with PET revealed parietal hypometabolism, morepronounced on the right. The extensive genetic analysis revealed pres-ence of deletions in the genes STXBP1 (9q34.11) and MACROD2(20p12.2). Despite initial refractory, she is now seizure free on carbamaz-epine and vigabatrin.

Conclusion: The case described above is a particular example of presen-tation of an early epileptic encephalopathy that is believed to be primarilyassociated with STXBP1 disruption. We discuss the contribution of addi-tional gene MACROD2 deletion to the epileptic phenotype.

43

Abstracts


p146ANALYSIS OF COPY NUMBER VARIATIONS AFFEC-TION ION CHANNEL GENES IN IDIOPATHIC GENER-ALIZED EPILEPSY -A CASE-CONTROL SURVEYUSING A CUSTOMIZED MICROARRAY-BASED COM-PARATIVE GENOMIC HYBRIDIZATION (IONCHAN-NEL ARRAY�)P. Striano*, R. Paravidino*, M. Pezzella*, G. Giudizioso*,M. Montera*, A. Bianchi�, A. Coppola�, F. Dagna Bricarelli§,D. A. Coviello§, C. Minetti*, and F. Zara**Gaslini Institute, University of Genova, Genova, Italy; �Arezzo,Italy; �Institute of Neurology, University College London,London, UK; and §Galliera, Genova, Italy

Purpose: To perform an extensive search for genomic rearrangements(CNVs) involving ion channel genes in patients with idiopathic general-ized epilepsy (IGE) by custom microarray-based comparative genomichybridization (custom array-CGH).

Method: Probands with familial (i.e., at least two first-degree or threeaffected relatives) IGE (classified according to the ILAE classification,1989) and 110 healthy controls were screened by custom CGH-arraydesigned to identify small CNVs affecting 429 candidate epileptogenicgenes. This IonChannel array� Agilent platform has 60.000 probes at theminimum resolution of 100 bp in exons and of 1000 bp in introns. Segre-gation analysis will be also performed.

Result: One-hundred twenty probands from familial IGE and 110healthy controls have been. CNVs involving ion channel genes wereidentified in both patients (mean size 412 Kb) and controls (mean size354 Kb). In patients, we identified chromosomal microrearrangementsinvolving different epilepsy candidate genes, including GABRG2, GAB-RAA1/A4, SCN1B, KCNE1/2, KCND2, TRPV2. Segregation analysis isongoing for many cases but intragenic CNVs affecting GABRG2 andKCND2 were found in affected parents.

Conclusion: IGE patients show a significantly increased burden of ionchannel genes-rich CNVs. The identification of rearrangements affectingstrong candidate epilepsy genes (e.g., GABRG2, KCND2) provides acompelling evidence that this method is a promising, powerful approachto improve dissection of complex pathogenesis of IGE.

p147GENETIC ANALYSIS OF SPORADIC ALTERNATINGHEMIPLEGIA OF CHILDHOODA. Ishii*, Y. Saito�, M. Sasaki�, and S. Hirose**Fukuoka University, Fukuoka, Japan; and �National Center ofNeurology and Psychiatry, Tokyo, Japan

Purpose: To find candidate genes for Alternating Hemiplegia of Child-hood (AHC). AHC begins with abnormal eye movement at around 2–3months of age; hemiplegia follows at about 6–7 months; and later, quad-riplegia (Alternating distonia in children) appears. Convulsions beginaround the age of six, often causing tonic-clonic seizures and tonic sei-zures. Ultimately, paralysis and the patient's resultant bed-ridden condi-tion lead to severe intellectual disabilities. Blood and spinal fluid tests,MRI images, and EEGs give no indication of the disease. The genesresponsible for AHC are unidentified and its molecular genesis remainsunclear.

Method: In eight Japanese AHC patients, we investigated the geneticabnormalities of four genes encording a1 subunit of voltage-gatedsodium channel, a2 subunit of ATP-dependent Na/K pump, a1 subunit ofP/Q-type voltage-dependent calcium channel and a1B subunit of P/Q-type voltage-dependent calcium channel – respectively, SCN1A,ATP1A2, CACNA1A and CACNA1B genes.

Result: Three polymorphisms in SCN1A, three in CACNA1A, and fourin CACNA1B were identified in eight Japanese AHC patients. Of thesepolymorphisms, one in SCN1A, three in CACNA1A, and two in CAC-NA1B showed amino acid substitutions. Statistical examination showedno significant differences between healthy subjects and those with poly-morphisms.

Conclusion: Since AHC onset in our patients was within seven daysafter birth, we believe that AHC is caused by genetic abnormalities.

p148GENETICS OF EPILEPSY, A DUTCH COHORT STUDYB. Berghuis*, G. De Haan�, B. Koeleman�, J. W. Sander§, andD. Lindhout–

*SEIN, Zwolle, The Netherlands; �Stichting EpilepsieInstellingen Nederland (SEIN), Heemstede, The Netherlands;�University Medical Center Utrecht, Utrecht, The Netherlands;§UCL Institute of Neurology, London, UK; and –UniversityMedical Centre Utrecht, Utrecht, The Netherlands

Purpose: To identify genetic variants for disease susceptibility in epi-lepsy, genetic variants that contribute to refractoriness to antiepilepticmedication and genetic variants involved in common side effects of an-tiepileptic medication. We hypothesize that carriers of genetic mutationsthat cause epilepsy present a distinct and recognizable clinical pheno-type.

Method: The studypopulation exist of patients attending our outpatientepilepsy clinics, with a firm diagnosis of epilepsy, regardless of type.Characteristics of the epilepsy, including types and frequency of seizures,neurophysiology, imaging and response to medication are documentedfor each patient. We plan to perform Next Generation Sequencing, Gen-ome Wide Association Studies and Copy Number Variation analysis insearch for genetic variants in genes already known to cause epilepsy infamilies, associated with hyponatriema caused by carbamazepine, associ-ated with obestiy and valproate use and with influence on anti-epilepticdrug metabolism and transport.

Result: Inclusion of patients started September 2010. At the start of2012 over 700 patients provided informed consent and their DNA wassampled. Clinical phenotype was described of 453 patients. 83%(n=375)of patients had a focal epilepsy, 12%(n=56) a generalized epilepsy,5%(n=22) was not well defined. 34%(n=155) of the epilepsies weresymptomatic. 82% of patients had ever used carbamazepine, oxcarbazineor both. We plan to test for genetic variation in vassopressin pathwaygenes that may contribute to hyponatriema induced by these drugs.

Conclusion: The main outcome of this project will be a description ofclinical factors correlated to specific genetic risk variation, to enable clin-ical guidelines for early diagnosis and personalized treatment.

p149CLINICAL FEATURES OF EPILEPSY IN DENTATORU-BRAL-PALLIDOLUYSIAN ATROPHY PATIENTSH. Nakano, M. Kinoshita, and H. SawadaNational hospital of Utano, Kyoto-shi, Japan

Purpose: We assessed the clinical features in dentatorubral-pallidoluy-sian atrophy patients who had epileptic seizures.

Method: We included 5 DRPLA patients from different families (5men; mean age, 31.2 years) who had expanded CAG repeat in DRPLAgene and epileptic seizures. And analyzed their clinical features based onmedical recording.

Result: All patients had marked dementia and cerebellar ataxia. Apatient could perform simple verbal communication but other 4 patients

44

Abstracts


could utter only fragmented words or couldn't speak. The mean diseaseduration was 17.6 years. Three patients had positive family history. Themean onset age of epileptic seizure was 13.6 years. All patients had gen-eralized tonic clonic seizures and 2 also had partial seizures. The fre-quency of generalized seizures was monthly in 2 patients and yearly in 1.Two patients had no seizure over 1 year. The frequency of myoclonuswas daily in 3, and monthly in 1. One patient had no myoclonus. Electro-encephalography showed generalized epileptiform discharges in 4patients and both generalized and focal epileptiform discharges in 3. In 2patients, localization of focal epileptiform discharges corresponded toseizure semiology. Number of antiepileptic drugs co-administered was 5in 1 patient and 4 in 4.

Conclusion: DRPLA is one of the primary disease which induces pro-gressive myoclonus epilepsy whose seizures in young onset patients areintractable. Our data suggest that in some patients critical seizures maybe controlled with co-administration of multiple drugs.

p150EFFECT OF CYP3A4*1G/*18/*19 AND CYP3A5*3 GENO-TYPE ON SERUM CARBAMAZEPINE CONCENTRA-TIONS AT STEADY-STATE IN HAN CHINESEEPILEPTIC PATIENTSJ. Wang, and Z. HongInstitution of Neurology, Shanghai, China

Purpose: The present study aimed to assess the distribution of theCYP3A4*18/*19/*1G and CYP3A5*3 genotype in Han Chinese epilep-tic patients with carbamazepine (CBZ)-therapy and their effect on serumCBZ concentrations at steady-state.

Method: The serum concentrations of CBZ and the CYP3A4*18/*19/*1G and CYP3A5*3 genotype was determined in 247 Han Chineseincluding 177 monotherapy patients and 70 valproate-add-on patients.

Result: In total group, the mutations of CYP3A4*18/*19 were notfound. And the normalized concentrations of CBZ (concentration/(weight·dose)) were 0.25€0.067lg·kg·d (ml·g)-1 for CYP3A4*1Gnon-expressors (AA and AG allele) and 0.28€0.080lg·kg·d (ml·g)-1 forCYP3A4*1G expressor (GG allele)(P=0.003). It was0.23€0.060lg·kg·d (ml·g)-1 for CYP3A5*3 expressors (AA and AGallele) and 0.30€0.076lg·kg·d (ml·g)-1 for CYP3A5*3 non-expressors(GG allele)(P<0.0001). The similar result was found in monotherapy andadd-on group with CYP3A5*3 genotype, but not in add-on group withCYP3A4*1G. In monotherapy group, the normalized concentrations ofCBZ were 0.25€0.065 lg·kg·d (ml·g)-1 for CYP3A4*1G non-expres-sors and 0.28€0.074 lg·kg·d (ml·g)-1 for CYP3A4*1G expressor(P=0.001). It was 0.24€0.054lg·kg·d (ml·g)-1 for CYP3A5*3 expres-sors (AA and AG allele) and 0.31€0.072lg·kg·d (ml·g)-1 forCYP3A5*3 non-expressors (GG allele) (P<0.0001). In add-on group, thenormalized concentrations of CBZ were 0.24€0.070 lg·kg·d (ml·g)-1

for CYP3A4*1G non-expressors and 0.26€0.087 lg·kg·d (ml·g)-1 forCYP3A4*1G expressor (P=0.257). It was 0.21€0.068lg·kg·d (ml·g)-1

for CYP3A5*3 expressors (AA and AG allele) and 0.29€0.078lg·kg·d(ml·g)-1 for CYP3A5*3 non-expressors (GG allele) (P<0.0001).

Conclusion: In generally, the CYP3A4*1G, CYP3A5*3 genotypeaffected the CBZ concentrations in Han Chinese patients that the normal-ized concentrations of CBZ in patients with CYP3A4*1G expressor (GGallele) and CYP3A5*3 non-expressors (GG allele) was higher than AGand AA allele. And it is a factor that may contribute to inter-individualvariability in CBZ disposition in Han Chinese epileptic patients.

p151RECURRENT RECIPROCAL GENOMIC REARRANGE-MENT OF 17Q12 AS A CAUSE OF GEFS+K. Hardies*, E. Peeters�, A. Suls*, S. Weckhuysen*,P. Holmgren*, W. Van Paesschen�, and P. De Jonghe*

*University of Antwerp, Antwerp, Belgium; and �UniversityHospital Gasthuisberg, Leuven, Belgium

Purpose: Determine frequency of recurrent reciprocal genomic rear-rangements of 17q12 in generalized epilepsy with febrile seizures plus(GEFS+).

Method: De novo copy number variations (CNV) and inherited genomicrearrangements have been recognized as causal variants and risk factorsfor a variety of diseases. So on, CNV analysis has become an establishedtool in clinical diagnostics. Molecular karyotyping was performed withthe 180k Cytosure ISCA v2 array (OTG) in a proband of a four generationGEFS+ family with eight affected members. Multiplex Amplicon Quan-tification was used for segregation analysis of the findings and screeningof a follow up cohort.

Result: Initially a 2.12Mb microduplication of 17q12 was identified in aproband whom has febrile, myoclonic, tonic-clonic seizures, absencesand intellectual disability (ID). Subsequent analysis showed clear co-seg-regation of the variant with the phenotype in four additional family mem-bers. The follow up screening of other families, patients and controls ison going.

Conclusion: Recent findings revealed that recurrent reciprocal genomicrearrangements of 17q12 (both deletions and duplications) can be associ-ated with a combination of all previously described symptoms. Ourresults confirm, however, that microduplications of 17q12 can be associ-ated with a restricted phenotype consisting of ID and seizures but withoutrenal disease or diabetes. Epileptic phenotypes are often poorly describedbut our family falls within the GEFS+ spectrum. The presence of IDcould be a clue for CNV screening but is not a requirement as mostaffected family members had a normal intellect. It remains an intriguingquestion how these rearrangements can lead to specifically epilepsy.

p152A RAT MODEL FOR LGI1-RELATED EPILEPSYS. Baulac*, S. Ishida�, T. Mashimo�, M. Boillot*, N. Fumoto�,M. Kuwamura�, Y. Ohno§, A. Takizawa�, T. Aoto–, M. Ueda–,A. Ikeda**, R. Takahashi�, E. Leguern*, and T. Serikawa�

*ICM, Paris, France; �Institute of Laboratory Animals, Kyoto,Japan; �Veterinary Pathology, Saka, Japan; §Laboratory ofPharmacology, Osaka, Japan; –PhoenixBio Co. Ltd,Utsunomiya, Japan; and **Graduate School of Medicine, KyotoUniversity, Kyoto, Japan

Purpose: Mutations of the leucine-rich glioma-inactivated 1 (LGI1)gene cause autosomal-dominant partial epilepsy with auditory featuresalso known as autosomal-dominant lateral temporal lobe epilepsy (AD-LTE). Besides, immune-mediated disruption of LGI1 results in seizuresand limbic encephalitis. We aimed to generate an animal model for Lgi1-related epilepsies.

Method: The ENU (N-ethyl-N-nitrosourea)-mutagenized F344/NSlc ratarchive (KURMA: Kyoto University Rat Mutant Archive) of the NBRP-Rat project was screened for mutations in the Lgi1 gene. We recoveredan Lgi1-targeted rat carrying a missense mutation (L385R).

Result: We provided evidence that L385R mutation prevented secretionof Lgi1 protein in COS7 transfected cells. However, low abundance ofL385R-Lgi1 protein was found in the brains and primary cultured neuronsof Lgi1-mutant rats, suggesting that mutant protein is destabilized in vivo.

Phenotype of homozygous and heterozygous L385R-Lgi1 mutant ratswas investigated.

Behavioral observations and intracranial electroencephalographicmonitoring recapitulated several features of the human disease: homozy-gous L385R-Lgi1 mutant rats by P10 experienced early-onset spontane-ous epileptic seizures, and died prematurely. Moreover, adultheterozygous L385R-Lgi1 rats exhibited markedly higher susceptibilityto sound-induced seizures (generalized tonic-clonic seizures) compared

45

Abstracts


to control animals. Audiogenic seizures were suppressed by the adminis-tration of several antiepileptic drugs (carbamazepine, phenytoin and lev-etiracetam) commonly used to treat partial seizures, but not byethosuximide, a drug of choice for absence seizures.

Conclusion: Our findings provide the first rat model harboring a mis-sense mutation in the Lgi1 gene, yielding a complementary model to clas-sical knockout mice to study Lgi1-related epilepsies.

p153EPILEPSY ASSOCIATED WITH 22Q11.21 MICRODU-PLICATIONS. Tang*, E. Hughes�, and D. K. Pal**King's College London, London, UK; and �King's HealthPartners, London, UK

Purpose: Epilepsy is a little known association in 22q11.21 duplication.Here we describe the phenotype of affected children from two large data-bases of genomic variation.

Method: After finding an index affected child, we searched the clinicalgenetics database [http://bbgre-dev.iop.kcl.ac.uk] of 10,397 individuals,as well as DECIPHER database.

Result: The index child carried a de novo 2.49MB duplication of22q11.21 (between LCR22B and LCR22E) as well as a maternally inher-ited 15kB microdeletion of chromosome 2p16.3 in an intronic region ofneurexin-1. He presented age five with atypical benign partial epilepsywith left centro-temporo-parietal discharges, focal atonic seizures pro-gressing to ESES. He also had some autistic spectrum, attentional andmemory difficulties but no MRI evidence of malformation. Both parentswere asymptomatic. In BBGRE we found 30 other individuals with22q11.21 duplications: 19 had developmental delay; 8 had autism spec-trum disorders; 17 had dysmorphism or congenital malformations; andonly one other individual had epilepsy (infantile spasms). In DECIPHER,we identified 73 individuals with 22q11 duplication and variable pheno-types of whom only two were reported to have epilepsy with no furtherdetails. In the literature, five children with 22q11.21 dup have beenreported with epilepsy or abnormal EEG and a variety of other features:one with nocturnal focal seizures and waking state epileptic spasms(Shimojima, 2010); another with occipital epilepsy and polymicrogyriain a child with co-existing inverted 9p dup/del (Mosca, 2009).

Conclusion: The 22q11.21 duplication is associated with a variable phe-notype; epilepsy is an uncommon association and both focal nocturnalseizures and epileptic spasms are specific findings.

Medical Therapy and Pharmacology 1Monday, 01 October 2012

p154LACOSAMIDE IN ADD-ON IN CHILDREN AND YOUNGADULTS AFFECTED BY DRUG-RESISTANT EPILEPSYD. Battaglia, C. Brogna, I. Contaldo, F. Perrino, E. Albamonte,E. Losito, S. Veltri, G. Leo, D. Ranalli, and D. LettoriCatholic University, Rome, Italy

Purpose: To evaluate efficacy and tolerability of LCM in add-on withtraditional sodium channel - blocking AED [SCB (+)] and other AED[SCB (-)] in children and young adults with drug-resistant epilepsy

Method: 27 patients, aged between 3 and 31 years, affected by refractoryepilepsy, were enrolled and divided in 2 groups: 20 patients treated byLCM in add on with SCB (+) (group A), and 7 patients treated by LCM inadd on with SCB (-) (group B). Epilepsy type consisting of symptomatic(23) and presumed symptomatic (3) focal epilepsy. Neurological examina-

tion, EEG, ECG, and plasmatic levels of AED were performed before andafter LCM treatment. The efficacy was calculated in relation to seizure fre-quency reduction using parents’ diaries. LCM dose ranged between 200and 400 mg/die in young adult and 6 mg/kg/die in children.

Result: The follow-up ranged from 4 to 18 months. At the end of the fol-low-up, seizure frequency reduction was of ‡75% in 9 patients (45%) ofthe group A and in 2 patients (28.5%) of the group B. In only 1 patientLCM was discontinued because of inefficacy. Diplopia, nausea and dizzi-ness reported during the titration period in 11 patients of the group A dis-appeared reducing the associated sodium channel - blocking AED.

Conclusion: LCM showed good tolerability in add on in pediatric popu-lation. Despite the small sample of the group B, our preliminary data sug-gested that LCM seems more efficacy in reducing seizure frequency inpatients with refractory focal epilepsy treated with concomitant tradi-tional sodium channelblocking AED.

p155COST UTILITY ANALYSIS OF PHENOBARBITAL ASMONOTHERAPY AMONG ADULT EPILEPSYPATIENTS IN A TERTIARY HOSPITALP. P. PingulPhilippine Neurological Association, Quezon City, Philippines

Purpose: To evaluate the cost-utility profile of Phenobarbital as mono-therapy among adult epilepsy patients in a tertiary hospital.

Method: Adult epilepsy patients receiving Phenobarbital for at least ayear, consenting and capable of answering the questionnaire wereincluded in the study. The overall costs of treating epilepsy in this popula-tion in terms of the direct costs (visits, hospitalizations, diagnostics, treat-ment, transportation, nursing care) and indirect costs (employment-related losses) were determined. Outcome measures were described inthis study as seizure frequency, patient satisfaction, adverse symptoms,and quality-of-life measurement using a multiattribute utility scale toderive QALYs (quality adjusted life years).

Result: Monotherapy with Phenobarbital has shown high efficacy with77% of patients experiencing a seizure attack of only once every 2months or less. Tolerability is also good as 84% of the populationexpressed satisfaction with the drug despite 41% experiencing sideeffects of drowsiness and forgetfulness. Overall health state preference of0.78 using the HUI-III among these patients on Phenobarbital is compa-rable to those with self-reported epilepsy from other studies. The overallcost of treating epilepsy with Phenobarbital per patient per year was Php5, 255.62. The overall gain in health as expressed in QALYs per patientwas 41.80, and the cost per QALY gained was Php 124.33.

Conclusion: Phenobarbital monotherapy among adult epilepsy patientshas shown overall favorable results, particularly in terms of cost per qual-ity adjusted life years gained, with reference to current pharmacoeco-nomic standards.

p156EFFECTS OF VALPROIC ACID TREATMENT IN LIPIDPROFILE AND HS-CRP IN EPILEPTIC PATIENTSS. Markoula*, D. Chatzistefanidis*, C. Tzallas�, G. Lagos*,E. Bairaktari�, and A. P. Kyritsis**University of Ioannina, Ioannina, Greece; and �UniversityHospital of Ioannina, Ioannina, Greece

Purpose: To investigate the role of daily dose, valproate's blood leveland treatment duration in lipid profile alterations and HS-CRP bloodlevel of epileptic patients receiving valproic acid.

Method: Epileptic patients receiving valproic acid were consecutivelyrecruited. Sex, age, daily dose and duration of treatment were recorded.

46

Abstracts


Waist perimeter, weight and height were measured. Fasting blood sam-ples were collected to measure triglycerides, LDL, HDL, total cholesteroland valproic acid along with HS-CRP blood level.

Result: Forty-six patients (29 males and 17 females) were included.Mean age was 39.5 years (males 41.2 years, females 36.6 years). Dailydose level was not related to BMI, waist perimeter, total cholesterol, tri-glyceride, LDL or HDL level. Treatment duration over 24 months wasrelated to a significant increase in BMI and total cholesterol level (p <0.05), as well as LDL level (p=0.057). This effect was statistically signifi-cant only in men, although women showed a similar trend. HS-CRPblood level was positively related to drug's daily dose and blood level.

Conclusion: Alterations in lipid profile and body weight are mainly aresult of treatment duration. On the other hand, HS-CRP blood level waspositively influenced by daily dose and drug blood level. This knowledge isimportant when deciding the daily dose and treatment duration in patientswith metabolic syndrome and/or evidence of cardiovascular disease.

p157RECTAL CARBAMAZEPINE AS EFFECTIVE TREAT-MENT FOR ESCALATING SEIZURES AND STATUS EP-ILEPTICUSD. J. Cordato*, V. I. Patel*, and R. G. Beran�

*Liverpool Hospital, Liverpool, NSW, Australia; and �GriffithUniversity, South Port, Qld, Australia

Purpose: Carbamazepine (CBZ) is the gold standard anti-epileptic drug(AED) for focal onset seizures. The aim of this study is to examine thepotential use of rectal (PR) CBZ as an alternative to parenteral AEDs instatus epilepticus (SE) or cluster seizures.

Method: Oral CBZ syrup was given PR using 400mg equivalent aliqu-ots. Serum CBZ levels were requested 30 to 60 minutes after administra-tion to confirm absorption and achievement of minimum therapeuticlevels (total CBZ > 20 lmol L-1). Where levels were sub-therapeutic, theprocedure was repeated using 400mg CBZ bolus aliquots until therapeu-tic levels were achieved.

Result: 6 patients received PR CBZ, to manage cluster seizures follow-ing initial treatment with IV benzodiazepines. All patients’ seizuresceased and therapeutic CBZ levels were achieved in 5 of 6 subjects with5–10 hours of initial CBZ dosing.

Conclusion: PR CBZ is a viable alternative to parenteral AEDs inpatients presenting with SE or cluster seizures.

p158PHASE III TRIALS OF ADJUNCTIVE PERAMPANEL, ASELECTIVE AMPA RECEPTOR ANTAGONIST, INPATIENTS WITH TREATMENT-RESISTANT PARTIAL-ONSET SEIZURES: ANALYSIS OF PATIENT DEMO-GRAPHICS AND BASELINE CLINICAL CHARACTER-ISTICSV. Villanueva*, G. L. Krauss�, C. Brandt�, D. Squillacote§,H. Yang§, D. Kumar§, and A. Laurenza§

*Hospital Universitario y Polit�cnico La Fe, Valencia, Spain; �

Johns Hopkins University, Baltimore, MD, USA; �BethelEpilepsy Centre, Mara Hospital, Bielefeld, Germany; and §EisaiNeuroscience Product Creation Unit, Woodcliff Lake, NJ, USA

Purpose: To describe demographics and baseline characteristics ofpatients in three phase III trials of adjunctive perampanel for treatment-resistant partial-onset seizures (studies 304, 305, 306).

Method: Patients were randomized to once-daily placebo, perampanel 2mg, 4 mg, 8 mg or 12 mg. Patient demographics, time since diagnosis,

seizure type and number of concomitant antiepileptic drugs (AEDs) weresummarized for the three studies.

Result: 388, 386 and 706 patients were included in the safety populationin studies 304, 305 and 306, respectively. Mean age was similar in eachstudy (36.0, 35.5 and 33.8 years for 304, 305, 306, respectively); 8.5–11.4% of patients were aged <18 years. Approximately half of patientswere female: 51.5%, 51.8% and 51.1%. The majority of patients werewhite (>65.0%); however, study 306 had a higher proportion of Asian/Chinese patients (34.6%) compared with 304 or 305 (1% and 10.9%,respectively). Mean time since diagnosis was 23.7, 22.0 and 19.1 years.At Baseline, simple partial seizures (without motor signs) occurred in36.9%, 34.5%, 29.7% of patients in 304, 305 and 306, respectively; sim-ple partial seizures (with motor signs) occurred in 33.0%, 27.7%, 30.2%;complex partial seizures occurred in 88.9%, 85.0%, 84.0%; and complexpartial plus secondary generalization occurred in 71.9%, 67.9%, 69.0%.The mean number of AEDs received in the past 5 years was 2.8, 3.2 and3.4 for patients entering 304, 305 and 306, respectively.

Conclusion: Patient populations in the three phase III trials of adjunc-tive perampanel for treatment of refractory partial-onset seizures weresimilar.

Support: Eisai Inc.

p159EFFICACY AND SAFETY OF LACOSAMIDE ASADJUNCTIVE THERAPY IN A COHORT OF CHILDRENWITH REFRACTORY PARTIAL-ONSET EPILEPSYJ. Kaleyias, A. Koukouletsos, A. Frimas, E. Tsekoura,A. Anagnostopoulou, A. Varvarigou, and S. MantagosUniversity Hospital of Patras, Patra, Greece

Purpose: To evaluate the efficacy and safety of lacosamide (LCM) asadjunctive treatment in a cohort of children with uncontrolled partial-onset seizures taking one to three concomitant AEDs (Guilhoto LM et al.Pediatr Neurol 2011; 44: 414–419).

Method: Retrospective review of charts identified 14 children (11males, mean age 10.7 years, range 4.5–17) with refractory partial-onsetseizures on LCM. Seizure count and side effect (SE) profile were main-tained during therapy. Good responders were defined those with ‡ 50%seizure frequency reduction. Statistical analysis was performed withSPSS.

Result: Causes of epilepsy included tuberous sclerosis complex (n=3),Rett (n=1), Aicardi (n=1), Sotos syndrome (n=1) and CP (n=2). The med-ian age of seizures onset was 2 years (Intraquartile range: IQR 1–5), med-ian length of follow-up 7 years (IQR 2–10) and the median duration onLCM was 23 months (range 3–48). The median number of AEDs beforeLCM was 7 (range 2–10). LCM dosage was 5 mg/k/d (range 3–10). Goodresponders were 50% (7/14) [(2/14 (14%)] became seizure-free and cur-rently in LCM monotherapy). In 7 children (50%) LCM had to be discon-tinued: 4 (28%) due to poor seizure control and 3 (21%) due to SEs andmarginal benefit. The mean number of previous AEDs in responders was4.4 while in non-responders was 8 (p <0.008). SEs were reported in 57%(8/14) (nausea, dizziness, somnolence, irritability, agitation); 3/14 sideeffects prompted LCM discontinuation [persistent somnolence (n=2),agitation (n=1)].

Conclusion: Lacosamide was demonstrated to be effective and safe inthis cohort of children with refractory partial-onset seizures.

p160THE EFFECTS OF ESLICARBAZEPINE AND R-LICA-RBAZEPINE ON SODIUM CURRENTS THROUGHNAV1.7 AND NAV1.8 CHANNELSS. Hebeisen*, K. Brady*, and P. Soares-Da-Silva�

47

Abstracts


*B’SYS GmbH, Witterswil, Switzerland; and �University ofPorto, Porto, Portugal

Purpose: Eslicarbazepine is the major active metabolite of eslicarbaze-pine acetate, a once-daily antiepileptic drug approved in Europe asadjunctive therapy for refractory partial-onset seizures in adults. Thisstudy was aimed to determine the effects of eslicarbazepine and R-lica-rbazepine on the human NaV1.7 and NaV1.8 sodium channels expressedin CHO cells.

Method: About 24–48 hours following transfection with human NaV1.7cDNA or NaV1.8 cDNA, cells were ready for electrophysiological exper-iments. The whole-cell patch-clamp technique was used to investigatethe effects of eslicarbazepine and R-licarbazepine on NaV1.7 and NaV1.8inward peak currents. Compounds were tested at -80 mV holding poten-tial. The affinity for the resting (KR) and inactivated (KI) states wasexamined after 15 s conditioning pre-pulses ranging from -120 mV to -40mV.

Result: At -80 mV holding potential, eslicarbazepine and R-licarbaze-pine were equipotent in inhibiting inward sodium currents throughNaV1.7 and NaV1.8 channels. However, the affinity of eslicarbazepinefor the inactivated (KI) state of Nav1.7 and Nav1.8 channels was 10 to 2times higher than that for R-licarbazepine. On the other hand, both com-pounds demonstrated a 10- to 5-times higher affinity for the inactivated(KI) state versus the resting (KR) state of the NaV1.7 channels, when com-pared to NaV1.8 channels.

Conclusion: Eslicarbazepine is endowed with a greater selectivity forthe inactive state of NaV1.7 and NaV1.8 sodium channels, when com-pared with R-licarbazepine.

p161SYMPTOMS AND COURSE OF INTOXICATION WITHMESUXIMIDEC. Brandt*, R. Hoepner�, B. Rambeck�, H. Ottenottebrock*, andT. W. May�

*Bethel Epilepsy Centre, Bielefeld, Germany; �St. JosefHospital, Bochum, Germany; and �Society for Epilepsyresearch, Bielefeld, Germany

Purpose: We report on a patient who presented with somnolence due tointoxication by the antiepileptic drug (AED) mesuximide (MSM). Thepurpose is to highlight the symptoms and treatment of MSM intoxicationand thus to raise awareness for a severe, but treatable condition in associ-ation with an AED that is used quite rarely nowadays.

Method: Case report.

Result: This 31-year-old, mentally impaired female patient sufferedfrom cryptogenic focal epilepsy with complex-partial and secondarilygeneralized tonic-clonic seizures since the age of twelve. She was admit-ted to a local hospital because of frequent falls supposed to be of epilepticorigin. Primidone 62.5 mg was added. When she was transferred to ourhospital, she was somnolent, vomited and responded undirectedly topainful stimuli. AED serum concentrations were as follows: Valproicacid 70.9 mg/L (reference range 40–100 mg/L), lamotrigine 8.1 mg/L (2–10 mg/L), n-desmethyl-mesuximide (NDM) 85.7 mg/L (10–40 mg/L).MSM was withdrawn, and she was treated by hemodialysis. After the firstcourse of hemodialysis NDM serum concentration had decreased, andthe patient was awake and responsive.

Conclusion: In somnolent patients treated with MSM and NDM levelsabove the ‘‘therapeutic range’’ (10–30 mg/L), drug intoxication – hereprobably chronic with a vicious circle of loss of appetite, add-on of primi-done and subsequent further increase of serum concentrations – shouldbe considered, adequate treatment initiated. Due to the rare use of MSMit is even more important to know the symptoms of intoxication in ordernot to miss a potentially life-threatening, treatable condition.

p162EFFICACY OF INTRAVENOUS LACOSAMIDE INPATIENTS WITH CONVULSIVE VERSUS NON-CON-VULSIVE STATUS EPILEPTICUSE. Y. Moreno, M. Peleterio, E. Bondy, J. Dom�nguez,E. Pardellas, and A. FernandezUniversity Hospital of Santiago de Compostela, Santiago deCompostela, Spain

Purpose: To compare the efficacy of intravenous lacosamide in patientswith convulsive versus non-convulsive status epilepticus.

Method: In this prospective, observational study, patients with convul-sive or non-convulsive SE that received iv lacosamide 200–400 mg iv for8 days were compared for electroencephalographic response and seizuretermination.

Result: Among 53 patients treated with iv lacosamide (mean dose 390.6mg for 8 days) as first- (34%) or second-line (66%) treatment for convul-sive (43.4%) or non-convulsive (56.6%) SE, the mean age was 55.2 yearsand 13.2% had prior epilepsy. The majority (73.6%) of patients had a co-morbid condition, predominantly hypertension (35.8%) and head injury(11.3%). The majority (79.2%) of patients received concomitant antiepi-leptic drugs, either 1 (34%), 2 (22.6%) or 3 (22.6%) agents, including mi-dazolam (54.7%), valproic acid (52.8%), and levetiracetam (30.2%) Theother AEDs were used in principle to stop the SE but the patients did notrespond and so we used lacosamide, however there are some exceptionsin whichinput was used. EEG confirmation of improvement following la-cosamide treatment was very positive in 56.6% of patients; 69.6% of theconvulsive and 46.7% of the non-convulsive SE groups. Among allpatients, 90.6% showed clinical improvement and there was no signifi-cant between-group difference for achievement of seizure termination,90% and 91.3% of the non-convulsive and convulsive SE groups, respec-tively. There were no reports of adverse events

Conclusion: Intravenous lacosamide was safe and similarly effective inpatients with convulsive or non-convulsive SE . Further investigationinto the use of lacosamide in the treatment of SE is warranted.

p163RESPONSE TO ADD-ON LACOSAMIDE IN PATIENTSWITH REFRACTORY EPILEPSYJ. Rodr�guez UrangaInstituto de Especialidades Neurol�gicas (IENSA), Sevilla,Spain

Purpose: Evaluate the efficacy and safety of adjunctive lacosamide inpatients with refractory epilepsy receiving up to 3 other antiepilepticdrugs.

Method: In this retrospective, observational, non-interventional, post-authorization study, patients with partial-onset seizures receiving 1–3AEDs received adjunctive lacosamide with doses from 100 to 400 mg(with a mean of 249.2 mg) for up to 5 months. Change in seizure fre-quency from pre- to post-treatment was assessed using the McNemar'stest of change.

Result: Sixty four patients of mean age 38.4 years with a median historyof epilepsy of 2 (1–5) months received add-on oral lacosamide (meandose 249.2 [100–400] mg/day) for a mean of 2.6 months. Most patientshad complex partial (34.4%), or complex (15.6%) or simple (9.4%) par-tial with secondary generalization subtype of epilepsy. For patientsreceiving 1, 2 or 3 AEDs, lacosamide was add-on treatment in 15(23.4%), 36 (56.3%) and 13 (20.3%), respectively. AEDs most com-monly used included levetiracetam (39.1%), carbamazepine (35.9), valp-roic acid (32.8%), lamotrigine (25%), and oxcarbazepine (20.3%).Initially, 63 patients (98.4%) had a seizure; by study end, this wasreduced to 47 (73.4%). Among the patients with baseline seizures, 25%

48

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had no seizures at end of treatment, a statistically significant reduction (p< 0.001). Median percentage reduction in seizure frequency was 56.7%.The response rate was 66.7% (seizure free [27%], reduction in seizurefrequency ‡50% [39.7%]), 15.9% had a reduction <50%, 17.5% had nochange in seizure frequency.

Conclusion: Add-on lacosamide was safe and effective in a broad rangeof patients with refractory epilepsy receiving 1–3 AEDs.

p164LEVETIRACETAM IS SUPERIOR TO CARBAMAZE-PINE-SR IN NEWLY DIAGNOSED EPILEPSY IN THEELDERLY: RESULTS OF THE STEP-ONE TRIALK. J. Werhahn*, E. Trinka�, J. Dobesberger�, C. Ruckes�, andG. Krmer§

*University Medical Center of the Johannes GutenbergUniversity, Mainz, Germany; �Paracelsus Medical University,Salzburg, Austria; �University Medical Center Mainz, Mainz,Germany; and §Swiss Epilepsy Centre, Zurich, Switzerland

Purpose: Rationale: A multicentre, double-blind, randomized, head-to-head comparison of levetiracetam (LEV), slow-release carbamazepine(CBZ-SR), and lamotrigine (LTG) in newly diagnosed elderly patientswith focal epilepsy (Study on the Treatment of Elderly Patients withOlder and Newer antiepileptic drugs; NCT00438451; EudraCT Number:2005-003324-19).

Method: Patients aged 60 years or above with new onset focal epilepsy(either at least one seizure and spike discharges on EEG or a relevantlesion on CT/MRI or a total of 2 spontaneous seizures) were eligible;those with symptomatic epileptic seizures due to acute (< 2 weeks) cere-bral lesions were excluded. Patients received LEV, CBZ-SR, or LTG(initial target dose of 1000mg LEV, 400mg CBZ-SR, or 100mg LTG) ina parallel group design over 58 weeks (6 weeks titration and 52 weeksmaintenance). Following titration patients were treated individually in adouble-blind manner depending on efficacy and tolerability on dosesbetween 500 – 3000mg for LEV, 200 – 1200mg for CBZ-SR, or 50 –300mg for LTG.

Result: A total of n=361 patients were randomized and n=359included in the intention-to-treat (ITT) population. Mean (€SD) agewas 71.8 € 7.5 for LEV (n=122, 34% female), 71.7 € 6.7 for CBZ-SR(n=120, 46%), and 70.7 € 7.4 for LTG (n=117, 41%). The mean num-ber of seizures prior randomization were 3.8 € 9.9, 4.8 € 10.8, and 2.7€ 3.1 for LEV, CBZ-SR, and LTG respectively (p < 0.05 for CBZ-SRvs. LTG, t-test). Based on the ITT population retention rates at 58weeks (primary endpoint) were 61% (95%CI: 53–70) for LEV, 46%(95%CI: 37–55) for CBZ-SR, and 56% for LTG (95%CI: 47–65) [p-values: overall 0.048; LEV vs. CBZ-SR 0.02, LEV vs. LTG 0.36, LTGvs. CBZ-SR 0.15, Fisher exact test]. Logistic regression revealed anodds ratio (OR) for a retention to treatment at 58 weeks of 1.838(95%CI: 1.092–3.093) for LEV vs. CBZ-SR, of 1.169 (95%CI: 0.689–1.984) for LEV vs. LTG, and of 0.636 (95%CI: 0.377–1.073) forCBZ-SR vs. LTG. The number of concomitant diseases significantlyinfluenced 58-week retention (OR 0.921; 95%CI 0.859–0.987), i.e.chances to remain on therapy were reduced by 7.9% with each addi-tional concurrent disease. There were no significant differences in sei-zure-freedom rates at week 30 (LEV 48%, CBZ-SR 39%, LTG 49%)and 58 (LEV: 43%, CBZ-SR 33%, LTG 38%) and in time-to-first sei-zure from randomization or after titration (after week 6).

Conclusion: Results demonstrate evidence of superiority of LEV inmonotherapy to CBZ-SR in new-onset focal epilepsy in the elderly. Asthe trial was not powered for the comparison of LEV and LTG there wasno significant difference between these treatment arms. However, resultsdo suggest that LEV should be among the first-line treatments in new-onset epilepsy of the elderly population. Future head-to-head trials withnovel or other antiepileptic drugs in the elderly population need to con-sider LEV as comparator.


p165ZONISAMIDE MONOTHERAPY IN ADULT PATIENTSWITH PARTIAL, GENERALIZED & COMBINED SEI-ZURES: FINDINGS OF A OPEN-LABEL, NON-COMPAR-ATIVE, OBSERVATIONAL STUDYA. Dash*, S. C. Mehta*, N. C. Manjunath�, A. Kiran�, B. Jyothi§,V. Bajpai–, V. N. Mathur**, S. Shah��, and D. Langade��

*Eisai Pharmaceuticals India Private Limited, Mumbai, India; �

Brain & Nerve Care Centre, Bangalore, India; �Ayush NeuroCare, Secunderabad, India; §Mediplus Clinic, Hyderabad,India; –Sai Neurology Clinic, Lucknow, India; **VivekanandaHospital, Hyderabad, India; ��Advanced Neurology &Superspecilaity hospital, Jaipur, India; and ��Institute ofMedical Science & Research, Faridabad, India

Purpose: To evaluate efficacy and safety of Zonisamide monotherapyin adult patients with partial, generalized & combined seizures.

Method: In this open, non-comparative, multi-center, observationalstudy, 59 patients (36 males, 23 females) having partial, generalized andcombined seizures were treated with Zonisamide monotherapy (100–500mg/day) for 24 weeks. Seizure frequency, clinician's global assess-ment of response to therapy (CGART) and patient's global assessment oftolerability to therapy (PGATT) were assessed every 4 weeks. Primaryoutcome was reduction in seizure frequency and secondary outcomeswere responder rate (‡50% reduction in seizure frequency) and seizurefreedom over 24 weeks. Adverse events were recorded during the studyperiod. Change in seizure frequency from baseline was analyzed byFriedman test (non-parametric repeat measures ANOVA).

Result: Fifty one patients completed 24 weeks study period, and 8 didnot complete the study (4 lost to follow up, 3 due to medication error,and 1 withdrew due to adverse event). Mean percent reduction in sei-zure frequency at 24 weeks was 78.02% (95% CI 61.75–131.02). After24 weeks, the responder rate was 74.29% (26/35), whereas 24 weeksseizure freedom was 22.86% (8/35). Adverse events were reported in 3(5.08%) patients, of which 1 (1.69%) patient each reported loss ofappetite, dizziness, and aggressive behavior with sleep disturbance.Patient reporting aggressive behavior with sleep disturbance withdrewfrom the study.

Conclusion: Zonisamide monotherapy demonstrates favorable efficacyand tolerability in adult patients with partial, generalized & combinedseizures, however small sample limits the generalization of the findings.

p166PHASE III, DOUBLE-BLIND, RANDOMISED, PLA-CEBO-CONTROLLED TRIAL ASSESSING EFFICACYAND SAFETY OF ADJUNCTIVE ZONISAMIDE THER-APY IN PAEDIATRIC PATIENTS WITH PARTIAL-ONSET SEIZURES: PRELIMINARY ANALYSIS OFEFFECTS ON COGNITIONA. Rosati*, J. Segieth�, L. Giorgi�, and R. Guerrini**Children's Hospital Anna Meyer-University of Florence,Florence, Italy; and �Eisai Limited, Hatfield, UK

Purpose: Zonisamide is currently licensed for adjunctive treatmentof adults with partial seizures (with or without secondary generalisa-tion). A Phase III trial recently assessed the efficacy/safety of adjunc-tive zonisamide in paediatric patients with partial epilepsy. Presentedhere are preliminary results of assessments of cognition that wereincluded in the trial.

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Method: Paediatric patients (6–17 years) with partial epilepsy receivedadjunctive zonisamide 8 mg/kg/day (N=107) or placebo (N=100) for 20weeks (8 weeks titration, 12 weeks maintenance) in a Phase III trial.Effects on cognition (including power of attention, continuity of atten-tion, quality of working memory, speed of memory, and picture recogni-tion sensitivity index) were assessed in around 80 patients withintelligence quotient ‡75. Last observation carried forward (LOCF) andobserved case data were analysed using analysis of covariance.

Result: No treatment effect was observed on power of attention (pri-mary variable), continuity of attention, quality of working memory, andpicture recognition sensitivity index (p>0.05 for all). Some evidence ofimpairment with zonisamide was observed on speed of memory at finalvisit, but only for the LOCF analysis using reciprocal transformed rawdata (p=0.0275).

Conclusion: No significant effects on psychomotor/information pro-cessing speed, attention (focussed and sustained), working memory (ver-bal and visuo-spatial), or episodic memory (visual recognition) wereobserved following 20 weeks’ treatment with adjunctive zonisamide inpaediatric patients with partial epilepsy. Supported by Eisai

p167SEXUAL HORMONAL PROFILE OF EPILEPTIC MALEPATIENTS RECEIVING VALPROIC ACIDD. Chatzistefanidis*, S. Markoula*, A. Giaka*, C. Tzallas�,E. Bairaktari�, and A. P. Kyritsis**University of Ioannina, Ioannina, Greece; and �UniversityHospital of Ioannina, Ioannina, Greece

Purpose: To study the impact of daily dose level and duration of treat-ment on hormonal profile of male epileptic patients receiving valproicacid.

Method: Male patients receiving valproic acid and hospitalized in theDepartment of Neurology were consecutively recruited. Age, daily doseand duration of treatment were recorded. Blood samples were collectedto measure testosterone, sex hormone-binding globulin (SHBG), FSHand LH blood levels.

Result: Twenty six patients (mean age 37.9 years) were enrolled in ourstudy. Testosterone level was significantly higher in patients receivingvalproic acid doses of more than 2000 mg (mean testosterone value of 7.2ng/ml versus 4.1 ng/ml, p < 0.05). Additionally, FSH (2.8 IU/l vs 4.1 IU/l) and LH (2.8 IU/l vs 3.8 IU/l) blood levels were lower, while SHBGblood level was higher (62.3nmol/l vs 38.5 nmol/l) in patients receivingdoses higher than 2000 mg, although these differences didn't reach statis-tical significance. Regarding treatment duration, none of the differencesreached statistical significance, although there was a trend of increasedmean testosterone (5.3 ng/ml vs 4.1 mg/ml) and decreased LH blood lev-els (2.7 IU/l vs 4.5IU/l) when treatment duration was longer than 24months.

Conclusion: Testosterone blood level is significantly affected by a dailydose exceeding 2000 mg. There is a trend for higher SHBG and lowerFSH and LH blood levels, which may result from negative feedback oftestosterone, in patients receiving daily doses higher than 2000 mg.Treatment duration longer than 24 months caused a non-significantincrease in patients mean testosterone and decrease in LH blood level.

p168EFFICACY AND SAFETY OF ZONISAMIDE AS FIRSTADD-ON THERAPY IN ADULT PATIENTS WITH PAR-TIAL, GENERALIZED & COMBINED SEIZURESS. C. Mehta*, S. Shah�, V. N. Mathur�, N. C. Manjunath§,B. Jyothi–, B. Demudubabu**, V. Kumar��, V. Bajpai��,D. Langade§§, and A. Dash––

*Eisai Pharmaceuticals India Private Limited, Mumbai, India; �

Advanced Neurology & Superspecilaity hospital, Jaipur, India;�Vivekananda Hospital, Hyderabad, India; §Brain & Nerve CareCentre, Bangalore, India; –Mediplus Clinic, Hyderabad;**Caring Hands Neuro Centre, Vishakhapatnam, India; ��MetroHospital & Heart Institure, Noida; ��Sai Neurology Clinic,Lucknow, Indonesia; §§Institute of Medical Science & Research,Faridabad, India; and ––1. Eisai Pharmaceuticals India PrivateLimited, Mumbai, Mumbai, India

Purpose: To evaluate efficacy and safety of Zonisamide in adultpatients with partial, generalized & combined seizures.

Method: In this open, non-comparative, multi-center, observationalstudy, 113 patients (65 males, 48 females) having partial, generalized andcombined seizures were treated with Zonisamide (100–500mg/day) for24 weeks as first add-on to the primary antiepileptic drug of clinician'schoice. Seizure frequency, clinician's global assessment of response totherapy (CGART) and patient's global assessment of tolerability to ther-apy (PGATT) were assessed every 4 weeks. Primary outcome was reduc-tion in seizure frequency and secondary outcomes were responder rate(‡50% reduction in seizure frequency) and seizure freedom over 24weeks. Adverse events were recorded during the study period. Change inseizure frequency from baseline was analyzed by Friedman test (non-parametric repeat measures ANOVA).

Result: Eighty five patients completed 24 weeks study period, and 28did not complete the study (20 lost to follow up, 7 due to medicationerror, and 1 withdrew due to adverse event). Mean percent reduction inseizure frequency at 24 weeks was 71.21% (95% CI 57.94–103.88). After24 weeks, the responder rate was 76.81% (53/69), whereas 24 weeks sei-zure freedom was 30.88% (21/68). Adverse events were reported in 4(3.54%) patients, of which 2 (1.77%) patients reported loss of appetiteand one had weight loss (0.88%) during study. One (0.88%) patient waswithdrawn from the study due toincrease in seizure frequency.

Conclusion: Zonisamide demonstrates favorable efficacy and tolerabil-ity as first add-on in adult patients with partial, generalized & combinedseizures.

p169RETIGABINE - A CHALLENGE FOR THERAPEUTICDRUG MONITORINGU. Juerges, and B. J. SteinhoffEpilepsy Centre Kork, Kehl-Kork, Germany

Purpose: Retigabine (RTG) is a new antiepileptic drug that wasapproved and introduced in Germany in 2011. For most antiepilectic drugtherapies drug monitoring has proved a useful and valuable tool. The spe-cial feature of retigabine is its excessive metabolization. The majormetabolites are RTG-N-glucuronide and N-acetyl-RTG, where the N-glucuronide and RTG have a constant ratio of 25:1. Although we do notknow what kind of anticonvulsive properties the metabolites have, it ishelpful to quantify not only the active agent RTG, but the metabolitesalso. What method is suitable for analyzing retigabine and its metabolitesin serum or plasma?

Method: RTG is quantified with a mass spectrometric method. Thesodium adducts are analyzed as target ions: RTG-Na ion=326; acetyl-RTG-Na ion=296. Chromatographic settings include: column: 150x4Per-fectSil5lm, mobile phase: 1mM sodium acetate/methanol isocratic.Sample preparation via methanol precipitation and dilution of extractwith sodium acetate solution (0.2%). Internal standard.

Result: The quantification of RTG as sodium adduct allows a selectiveand sensitive analysis of RTG and the metabolite N-acetyl-RTG. Using apH neutral mobile phase and excluding all acidic additives allows to rep-resent the in vivo metabolite distribution. Solutions of pH < 6 lead to thedecomposition of N-glucuronide and so to falsely increased retigabine

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values. To obtain stable sodium adducts for RTG and N-acetyl-RTG anexcess of sodium ions is needed.

Conclusion: RTG drug monitoring via a selective and sensitive analysismethod is possible using mass spectrometry. The analysis as sodiumadduct in a pH neutral solution with sodium ion excess is recommended.

p170EFFECTS OF ESLICARBAZEPINE, R-LICARBAZEPINEAND OXCARBAZEPINE ON FAST AND SLOW INACTI-VATION OF VOLTAGE-GATED SODIUM CHANNELSC. Aires*, S. Hebeisen�, and P. Soares-Da-Silva�

*BIAL - Portela & Ca. SA, S¼o Mamede do Coronado, Portugal;�B’SYS GmbH, Witterswil, Switzerland; and �University ofPorto, Porto, Portugal

Purpose: Eslicarbazepine, the major (94.5%) active metabolite of es-licarbazepine acetate (ESL), preferentially enhances the slow inactiva-tion of voltage-gated sodium channels (VGSC). This study was aimed tocompare the effects of eslicarbazepine with the effects of R-licarbazepineand oxcarbazepine (OXC), two minor metabolites (5.0% and 0.5%,respectively) of ESL, on the fast and slow inactivated states of VGSCs.

Method: The whole-cell patch-clamp technique was used to investigatethe effects of eslicarbazepine, R-licarbazepine and OXC (all at 250 lM)on sodium channels endogenously expressed in N1E-115 cells, in condi-tions of fast and slow inactivation of sodium currents.

Result: Steady state fast inactivation curves were shifted in the hyperpo-larizing direction by OXC (-17 mV), but not by eslicarbazepine (-2.4mV) or R-licarbazepine (-3.2 mV). OXC-treated fast inactivated chan-nels required long pulses to recover (Dt = 391 ms), whereas eslicarbaze-pine- and R-licarbazepine-treated fast inactivated channels recoveredsimilar to control conditions (Dt = 11 ms). The voltage dependence of theslow inactivation (shift V0.5) for OXC, R-licarbazepine, and eslicarbaze-pine was -28.1, )31.9, and )31.2mV, respectively. For eslicarbazepine,R-licarbazepine and OXC the affinity to the slow inactivated state was5.9, 5.8, and 1.8 times higher than to the channels in the resting state,respectively. For eslicarbazepine, R-licarbazepine, and OXC, the timeconstants for entering the slow inactivated sate were 7.00, 7.03, and12.36 s, respectively.

Conclusion: Both eslicarbazepine and R-licarbazepine preferentiallyenhance the slow inactivation of VGSC, whereas OXC appears to modifykinetics and voltage-dependence of fast inactivation states.

p171RUFINAMIDE AND LENNOX-GASTAUT SYNDROME:EFFICACY, TOLERABILITY AND NEUROPSYCOLOGI-CAL OUTCOME IN YOUNG PATIENTSC. Cerminara*, M. Pinci*, A. Luchetti�, D. Battaglia�,P. Curatolo*, M. G. Marciani�, and A. Romigi�

*Tor Vergata University, Rome, Italy; �Catholic University,Rome, Italy; and �University of Rome Tor Vergata, Rome, Italy

Purpose: The aim of our study was to explore the effectiveness, safetyand tolerability of rufinamide in young patients with LGS. Neuropsyco-logical outcome has been valuated.

Method: 24 patients of 6–31 years with LGS. These were treated withrufinamide added to the baseline therapy at the mean dose of 38.7 mg/kg/die for a mean period of 44.5 weeks. Effectiveness was evaluated com-paring the frequency of seizure between baseline period and. 3 monthsand 12 months after treatment beginning. Neuropsycological assessmentswere performed at baseline and at end point.

Result: Rufinamide was effective on seizure in 58.3% of patientsalready after 3 months: 1 patient seizure free, 7 had ‡ 50% seizure

reduction in countable seizures and 6 had a 25–50% seizure reduction,while seizure frequency remained unchanged in 6. 9/14 responders had a‡ reduction in drop attack and 6/14 patients had ‡ 50% decrease in sei-zures. 11/24 patients reported mild adverse effects. 5 of 24 patients dis-continued the treatment after 3–5 months because of serious adverseevents. 19 remaining patients were observed for mean period of 44.5weeks. Efficacy on seizure frequency remained steady until the end ofthe study. Cognitive and adaptive assessments reperformed after 12months of rufinamide treatment showed that 19/24 patients didn't have achange in IQ and adaptive behaviour score.

Conclusion: Our data suggest that rufinamide may be effective and welltolerated in the treatment of young patients with LGS. Moreover rufina-mide treatment was associated with low incidence of cognitive and psy-chiatric adverse events.

p172EXPOSURE-RESPONSE MODELING OF LACOSAMIDEIN ADJUNCTIVE TREATMENT OF PATIENTS WITHPARTIAL-ONSET SEIZURESC. Laveille*, R. Schoemaker*, and A. Stockis�

*Exprimo, Mechelen, Belgium; and �UCB, Braine L’Alleud,Belgium

Purpose: To develop a retrospective exposure-response model for laco-samide based on daily seizure counts of individual patients with focal epi-lepsy and to identify potential prognostic factors in reducing seizurefrequency (SF) by performing a covariate analysis.

Method: Individual daily seizure records (N=210,234) were obtainedfrom 1308 patients who participated in three double-blind, placebo-con-trolled clinical trials (SP667, SP754, SP755). Probability of daily seizureswas estimated by nonlinear mixed effects modeling using statistical dis-tributions appropriate for count data. Plasma concentrations were esti-mated using a population pharmacokinetic model. Drug effect on seizurefrequency reduction was modeled using a Hill function.

Result: A negative binomial distribution with zero-inflation and Mar-kovian element provided the best fit for all phases (baseline, titration,maintenance). Patients who were not taking concomitant sodium channelblocking (SCB) anti-epileptic drugs (AEDs; 18% of population) under-went a greater SF reduction from baseline compared with patients takingconcomitant SCB AEDs (82%). The EC50 (trough concentration produc-ing half the maximum SF reduction) was 4.6lg/mL (90%CI 3.5–5.7lg/mL). Median SF reduction in improving patients was 23% (placebo),48% (lacosamide with SCB) and 70% (lacosamide with non-SCB) at la-cosamide 400mg/day.

Conclusion: An exposure-response relationship was demonstratedbetween lacosamide plasma trough concentration and SF reduction frombaseline in patients with uncontrolled focal seizures. The combination oflacosamide with non-SCB AED(s) resulted in greater reductions in SFcompared with the combination of lacosamide with SCB AED(s), asidentified previously (Sak� et al, CNS Drugs 2010; 24:1055–68).

UCB-sponsored.

p173QUALITY OF LIFE IN PATIENTS WITH MEDICALYREFRACTORY EPILEPSY TREATED WITH LEVETI-RACETAM AS A MONOTHERAPYD. P. Cvetkovska, and E. CvetkovskaUniversity Clinic for Neurology, Skopje, Macedonia

Purpose: To evaluate efficacy and tolerability of levetiracetam as amonotherapy in patients with medicaly refractory epilepsy

Method: The study was randomized, prospective of 12-month durationand included 16 patients with newly diagnosed epilepsy. We evaluated

51

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efficacy primary by evaluating reduction of seizure frequency and sec-ondary by improvement of quality of life using QOLIE 89 questionnaire.We also registered development of adverse effects.

Result: The patients were on age from 14–65 years. From seizures typesmost representing was patients with SGS 46.5% and from etiological fac-tors (by CT and MRI) most of the patients was with hyppocampal sclero-sis, tumors and trauma. Analysis of reduction of seizures frequency showsignificant reduction >50% in 56.25% of patients, <50% in 18.75% ofpatients and without effects in 18.75% patients, without significant dif-ferences by seizures types (p<0.05). The improvement of QOLIE 89score in levetiracetam treated patients was 72.5% also without significantdifferences by seizures types (p<0.05). Fatigue, somnolence, headache,and irritability were adverse effects considered drug-related and reportedin 6% of patients.

Conclusion: Our results suggest that levetiracetam is highly effective intreatment of patients with refractory epilepsy, probably due to reductionof seizure frequency, but also because of improvement of social, moodand cognitive function.

p174EFFECTS OF LACOSAMIDE AND CARBAMAZEPINEON HUMAN MOTOR CORTEX EXCITABILITYH. Peckolt, H. Rothkegel, G. Deuschl, and N. LangUKSH Campus Kiel, Kiel, Germany

Purpose: Lacosamide (LCM) and carbamazepine (CBZ) are antiepilep-tic drugs both acting on neuronal voltage-gated sodium channels. Patch-clamp studies have demonstrated that LCM enhances slow inactivationof voltage-gated sodium channels, and, in contrast to CBZ, does notaffect steady-state fast inactivation. The enhancement of slow inactiva-tion of sodium channels by LCM is a novel manner to modulate sodiumchannels and leads to normalization of activation thresholds and areduced pathophysiological hyper-responsiveness, thereby effectivelycontrolling neuronal hyperexcitability without affecting physiologicalactivity.

Method: The present study was designed to explore dose-dependedeffects of LCM on motor cortex excitability with transcranial magneticstimulation (TMS) in a randomized, double-blind, placebo-controlledcrossover trial in young healthy human subjects, and to compare the pat-tern of excitability changes induced by LCM with those of CBZ.

Result: The two antiepileptic agents show distinct patterns, with differ-ential neuronal inhibitory and excitatory subsystems involved.

Conclusion: TMS can be used for testing acute drug effects at the sys-tems level of the cerebral cortex in awake humans and offers a broadarray of measures of motor cortical excitability, which cover differentaspects of excitability, such as axon excitability, and distinct forms ofinhibitory and excitatory synaptic excitability.


p175A CLINICAL STUDY METHOD USED TO EVALUATETHE EFFICACY AND SAFETY OF NOVEL ANTIEPI-LEPTIC DRUG ESLICARBAZEPINE ACETATE IN EPI-LEPTIC CHILDREN WITH PARTIAL-ONSETSEIZURESF. Mota*, J. Moreira*, T. Nunes*, and P. Soares-Da-Silva�

*BIAL - Portela & Ca. SA, S¼o Mamede do Coronado, Portugal;and �University of Porto, Porto, Portugal

Purpose: Eslicarbazepine acetate (ESL) is a novel once-daily voltage-gated sodium-channel blocker approved in Europe for use in adults asadjunctive therapy for refractory partial-onset seizures (POS) with orwithout secondary generalisation. This phase III study aims to assess theefficacy and safety of ESL as adjunctive therapy in 252 children and ado-lescents (2 to 16-years old) with refractory POS, treated with 1 or 2AEDs.

Method: After an 8-week baseline-period, patients with >4 seizures/4-weeks will be randomised (stratified by age: 2–6; 7–12 and 13–16 years)in 1:1 ratio to ESL or placebo once-daily. Following titration to targetdose of 20 mg/kg/day over a 6-week period, they will enter a 12-weekmaintenance-period. The primary endpoint is the responder rate (at leasta 50% decrease in seizure frequency), based on patients’ seizure diaries.Secondary endpoints include changes in seizure frequency, the propor-tion of seizure-free patients and seizure duration and severity (Hague sei-zure severity scale). Safety will be assessed by adverse events, clinicallaboratory tests, physical and neurological examinations, and measure-ment of growth and development. An open-label extension with the pos-sibility of conversion to monotherapy in cases such as seizure freedomwill follow the double-blind phase.

Result: The study is expected to be completed by the end of 2012, andthe results will be reported thereafter.

Conclusion: ESL efficacy data in adults with POS cannot be extrapo-lated in this population. This study is designed to evaluate the risk/benefitratio as part of the clinical development plan of ESL in children.

p176DRUG RESISTANCE AND SEIZURE SEVERITY OFPATIENTS IN PARTIAL-ONSET SEIZURE REGISTRA-TION TRIALS OF PERAMPANEL COMPARED WITHRECENTLY APPROVED ANTIEPILEPTIC DRUGSG. L. Krauss*, F. Kerling�, V. Villanueva�, D. Squillacote§,H. Yang§, J. Zhu§, L. Verdian–, and A. Laurenza§

*Johns Hopkins University, Baltimore, MD, USA; �UlmUniversity, Ulm, Germany; �Hospital Universitario yPolit�cnico La Fe, Valencia, Spain; §Eisai NeuroscienceProduct Creation Unit, Woodcliff Lake, NJ, USA; and –EisaiLtd, Hatfield, UK

Purpose: Successive registration studies of new adjunctive antiepilepticdrug (AED) therapies recruit many patients resistant to newer AEDs. Wedescribe baseline seizure frequency and demographic factors in peram-panel registration trials in the context of 5 previously approved newer-generation AEDs.

Method: We evaluated baseline seizure severity and baseline AED usein registration trials for perampanel, levetiracetam, zonisamide, lacosa-mide, eslicarbazepine and retigabine.

Result: Mean patient ages (32.9–41.3 years) were similar across all 6AED registration trials; mean duration of epilepsy was similar for peram-panel (19.1–23.7 years) and the 5 other AEDs (15.7–25.4 years). Mediannumber of seizures/28 days at baseline was generally higher for peram-panel (9.3–14.3) versus other AEDs: levetiracetam (6.7–10.5); lacosa-mide (5.5–15.0); eslicarbazepine (6.7–9.0); and retigabine (7.9–12.1)(zonisamide data not available). More patients had a history of secondarygeneralized seizures in perampanel studies (67.9–71.9%) versus leveti-racetam (26.0–27.0%); zonisamide (21.0–24.0%); lacosamide (43.8–78.8%); eslicarbazepine (28.2–47.1%); and retigabine (23.2–33.7%). Ahigh proportion of these refractory patients required 3 concomitant AEDsat baseline in perampanel trials (28.9–38.6%) compared with most otherAEDs: levetiracetam 5.0–5.1%; zonisamide 21.7–28.8%; lacosamide0.0–36.9%; eslicarbazepine 0.0–9.9%; retigabine 0.0–33.8%. As the lastof these registration studies, concomitant AEDs in perampanel studies

52

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included all 2nd- and 3rd-generation AEDs available in 2008–2009;71.5% of patients received at least one ‘newer’ AED.

Conclusion: Compared with registration trials for previous 2nd- and3rd-generation AEDs, patients entering the perampanel trials generallyhad higher seizure frequencies, more often had histories of secondarilygeneralized seizures, and were receiving 3 concomitant AEDs.

Support: Eisai Inc.

p177PHARMACOKINETICS AND TOLERABILITY OF ZON-ISAMIDE IN PAEDIATRIC PATIENTS WITH EPI-LEPSY: RESULTS OF A PHASE II, OPEN-LABELSTUDYL. Giorgi*, and I. Chouette�

*Eisai Limited, Hatfield, UK; and �Eisai Europe Limited,Hatfield, UK

Purpose: Zonisamide is currently licensed for adjunctive treatment ofadults with partial seizures (with or without secondary generalisation).This study aimed to characterise the pharmacokinetics and tolerability ofzonisamide in paediatric epilepsy patients.

Method: In this Phase II, open-label study, 33 paediatric patients (aged5–15 years) with uncontrolled seizures received adjunctive zonisamide(1–12 mg/kg/day; administered twice-daily) for approximately 60 days.Steady-state pharmacokinetics, including observed maximum concentra-tion (Cmax), area under curve to 12 h (AUC0–12h), apparent oral clearance(CL/F) and total body weight-normalised CL/F (CL/F/TBW), wereassessed at zonisamide doses of 1, 7 and 12 mg/kg/day. Analysis was per-formed by age (5–11 and 12–15 years) and concomitant use of CYP3A4-inducing or non-inducing antiepileptic drugs (‘‘induced’’ and ‘‘non-induced’’ patients). Tolerability was assessed by evaluating adverseevents (AEs).

Result: Overall, 21/33 (63.6%) patients completed the study. Zonisa-mide pharmacokinetics were dose-dependent and peak–trough fluctua-tions were relatively small over each 12-h evaluation period. Althoughpatient numbers were too low for statistical comparison, the followingobservations were of note: for non-induced patients, Cmax, AUC0–12h

and CL/F were numerically lower, and CL/F/TBW was numericallyhigher, in patients aged 5–11 versus 12–15 years; in both age groups,Cmax and AUC0–12h were numerically lower, and CL/F and CL/F/TBWwere numerically higher, in induced versus non-induced patients.Overall, 81.8% patients reported treatment-related AEs; most com-monly, somnolence (30.3%), anorexia (27.3%), asthenia (21.2%), diz-ziness (15.2%) and nervousness (15.2%). Most AEs were mild/moderate in intensity.

Conclusion: Zonisamide displayed dose-dependent pharmacokineticsand was generally well tolerated in this paediatric epilepsy population.

Supported by Eisai.

p178LONG-TERM TOLERABILITY OF ZONISAMIDE INPAEDIATRIC PATIENTS WITH EPILEPSY: RESULTSOF A PHASE II, OPEN-LABEL, EXTENSION STUDYI. Chouette*, and L. Giorgi�

*Eisai Europe Limited, Hatfield, UK; and �Eisai Limited,Hatfield, UK

Purpose: Zonisamide is currently licensed for adjunctive treatment ofadults with partial seizures (with or without secondary generalisation).This study aimed to characterise the long-term tolerability of zonisamidein paediatric epilepsy patients.

Method: This was a Phase II, open-label extension of a pharmacokineticand tolerability study, in which paediatric patients with uncontrolled sei-zures received adjunctive zonisamide (1–12 mg/kg/day; administeredtwice-daily). Patients were grouped by age at entry: 5–11 (n=20) and 12–18 (n=9) years. Safety assessments included adverse events (AEs), vitalsigns, physical examination and clinical laboratory tests, conductedmonthly for the first 3 months, and then at 6 months. Some data were col-lected beyond 6 months since the original protocol specified treatment upto 12 months.

Result: Overall, 24/29 (82.8%) patients completed the study. Meanexposure to zonisamide was 259 days. In total, 24/29 (82.8%) patientsreported treatment-related AEs; most commonly, anorexia (37.9%), som-nolence (34.5%) and asthenia (24.1%). Most AEs were mild/moderate inintensity. Ten new serious AEs were reported in five patients, only two ofwhich were considered zonisamide-related. Few patients experiencedclinically relevant laboratory abnormalities. Overall, 75.0% patients hadbicarbonate levels below the normal range, and 28.6% had chloride levelsabove the normal range, at any time during the study. There were noreports of oligohydrosis, severe rash or renal calculi and no notablechanges in body weight.

Conclusion: Long-term zonisamide therapy was generally well toler-ated in these paediatric epilepsy patients. Given the small sample size,further studies are needed to confirm these findings.

Supported by Eisai.

p179EFFICACY AND TOLERABILITY OF LAMOTRIGINMONOTHERAPY IN NEWLY DIAGNOSED EPILEPSYI. Marinkovic*, S. T. Ristic�, H. Kocic�, J. Cukuranovic*, andD. T. Ristic§

*Medical Faculty of Nis, Nis, Serbia; �Clinical Centre of Nis,Nis, Serbia; �Medical faculty University of Maribor, Maribor,Slovenia; and §Institutae of Pulmonary Disaeses, Nis, Serbia

Purpose: Evaluation of Lamotrigine monotherapy outcome in epilepsyoutpatients and comparison of adverse effects, in patients with newly-diagnosed epilepsy.

Method: In open- label, non randomized, add-on trial over a period of2 years, from January 2010. until January 2012. we analysed efficacyand tolerability of lamotrigin monotherapy in total of 147 untreatedpatients (84 male) with a recent diagnosis of epilepsy (41 idiopathicgeneralized epilepsy, 96 localisation- related epilepsy, 10 unclassifiedepilepsy). The follow-up period was minimum six months. Efficacywas classified as:1. remission without adverse effects; 2. remissionwith adverse effects; 3. >50% seizure reduction; 4. <50% seizurereduction; 5. seizure worsening. We analysed age at onset, manifesta-tions and frequency of seizures, before and after treatment, tolerabilityand advese effects. Seizure frequency was compared before and aftertreatment.

Result: A total of 147 patients (median age 48.15 years, range 18–84)evaluable at this analysis. The median doses of lamotrigine was 250 mg./daily. Remission without adverse effects was obtained in 62 patients(42.17%); remission with adverse effects in 29 patients (19.72%); seizurereduction of >50% in 39 patients (26.53%); seizure reduction of <50% in14 patients (9.52%) and seizure worsening in 3 patients (2.04%). The tol-erability of lamotrigine was generally good. The most frequent adverseeffects were imbalance/dizziness (10.88%), headaches (6.80%), trem-bling (5.44%), epigastric discomfort (4.76 %), rash (2.72%). Therapywas withdrawn in 2 (1.36%) patients.

Conclusion: Our study suggests high efficacy and good tolerability oflamotrigin in patients with newlydiagnosed epilepsy.

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p180ANTIEPILEPTIC DRUG USE AND SEIZURE REFERRALPATTERNS BY NON-EPILEPSY SPECIALISTS AT ALONDON REGIONAL NEUROSCIENCE CENTRE: ACLINICAL AUDITD. P. Holland*, W. Hall�, A. Blochberger�, and H. Cock**St. George's, University of London, London, UK; and �St.George's Healthcare NHS Trust, London, UK

Purpose: Evidence based guidelines support the use of short term (7–14days), prophylactic antiepileptic drugs (AEDs) for acute provoked sei-zures and/or patients at very high risk, but with no evidence of longerterm benefit. Guidelines also recommend that all patients with suspectedseizures or epilepsy have minimum safety information provided, and arepromptly referred to an epilepsy specialist. We set out to audit clinicalpractice around stroke and neurosurgery patients with respect to AED ini-tiation and seizures against published guidelines.

Method: All in-patients initiated on AEDs under neurosurgery or stroketeams over a 4 month period were prospectively identified. Patients witha prior epilepsy diagnosis were excluded. Medical records were then ret-rospectively reviewed using a pre-designed audit proforma, includingdiagnoses, demographics, AED details (including duration), documentedindication, follow up and referral.

Result: 43 patients were identified of whom 1 died, and 2 were lost tofollow up. Of the 40 patients included in the study, 30 AED initiationswere undertaken by neurosurgery, meeting 59% of AED audit criteria.Stroke clinicians initiated AEDs in 10 patients, meeting 71% of AEDaudit criteria. Of the 20 who had seizures, 25% had documented counsel-ling, and 25% were referred to epilepsy services. At least one audit crite-ria was not met in 73% of patients.

Conclusion: Shortfalls exist in AED and seizure management in neuro-surgical and stroke patients, with clinical governance and financial impli-cations. Measures to promote the use of existing pathways and availableexpertise are now being implemented, and a re-audit planned.

p181SLOW AND FAST INACTIVATION OF VOLTAGE-GATED SODIUM CHANNELS BY ESLICARBAZEPINEAND CARBAMAZEPINEP. Soares-Da-Silva*, and S. Hebeisen�

*BIAL - Portela & Ca. SA, S¼o Mamede do Coronado, Portugal;and �B’SYS GmbH, Witterswil, Switzerland

Purpose: The efficacy of adjunctive eslicarbazepine acetate (ESL) inreducing the frequency of partial-onset seizures in adults receiving carba-mazepine (CBZ) or another antiepileptic drug was similar (Epilepsia, 50,454–463, 2009; Epilepsy Res., 89, 278–285, 2010). This study was aimedto determine the effects of eslicarbazepine, the major active metabolite ofESL, and CBZ on the fast and slow inactivated sates of voltage-gatedsodium channels (VGSC).

Method: The whole-cell patch-clamp technique was used to investigatethe effects of eslicarbazepine and CBZ (both at 250 lM) on sodium chan-nels endogenously expressed in N1E-115 cells, in conditions of fast andslow inactivation of sodium currents.

Result: Steady state fast inactivation curves were shifted in the hyperpo-larizing direction by CBZ ()12.0 mV), but not by eslicarbazepine ()2.4mV). Eslicarbazepine-treated fast-inactivated channels recovered simi-larly to control conditions (Dt = 11 ms), whereas CBZ-treated channelsrequired longer pulses to recover (Dt = 391 ms). CBZ shifted by )4.6mV, the voltage dependence of the slow inactivation, whereas for es-licarbazepine the shift V0.5 was )31.2 mV. For eslicarbazepine and CBZ,the affinity to the slow inactivated state was 5.9 and 1.7 times higher than

to the channels in the resting state, respectively. For eslicarbazepine andCBZ, the time constants for entering the slow inactivated state were 7.00and 14.49 s, respectively.

Conclusion: Eslicarbazepine does not share with CBZ the ability to alterfast inactivation of VGSC, but rather appears to modify the kinetics andvoltage-dependence of slow inactivation states.

p182CLINICAL EXPERIENCE WITH ORAL LACOSAMIDEAS ADJUNCTIVE THERAPY IN ADULT PATIENTSWITH UNCONTROLLED EPILEPSY: A MULTICENTRESTUDY IN EPILEPSY CLINICS IN THE UNITED KING-DOMR. D. Cary Elwes*, S. Kemp�, L. Flores*, K. Colbeck�,L. Nashef*, P. Goulding�, and M. P. Richardson�

*King's College Hospital, London, UK; �St Jame's Hospital,Leeds, UK; and �King's College London, London, UK

Purpose: To evaluate the efficacy and tolerability of add-on Lacosa-mide in an out-patient epilepsy clinic setting to obtain useful informationfor everyday practice.

Method: A retrospectively case note study of patients with refractoryepilepsy was carried out in whom lacosamide had been prescribed in 19hospitals across the United Kingdom.

Result: Four hundred and three patients were included (mean age 41.9years, 50.6% women, 18.1% with learning disabilities). Mean follow-upwas 11.6 months (range one day to 42 months). Most (86.9%) had symp-tomatic partial epilepsy and were taking a mean of two other antiepilepticdrugs. Retention rates were 80% at six months, 68% at one year and 45%tat two years. The efficacy of lacosamide was evaluated at three monthsand at the final FU. At three months one hundred and eight patients(31.1%) reported ‡50% seizure reduction and 32 (9.2%) were seizuresfree. At final FU 102 (37.5%) reported ‡50% seizure reduction and 28(9.8%) were seizures free. One hundred and ninety three patients (48.7%)reported adverse effects (AEs). The most frequent were sedation and diz-ziness, followed by nausea. Lacosamide was discontinued in 150 patients(38%), mostly due to AEs and lack of efficacy. No major neuropsychiat-ric complications were identified and outcomes in cases with learningdifficulties were similar to those without.

Conclusion: Lacosamide appears to be an effective and safe AED whenused as adjunctive therapy in patients with refractory partial epilepsy.

p183THE LONG-TERM EXPERIENCE OF MONOTHERAPYWITH OXCARBAZEPINE AND LEVETIRACETAM INTHE TERTIARY EPILEPSY CENTERJ. Lim, B. S. Kang, J. Byun, B. S. Park, J. W. Shin, Y. S. Kim,K. Chu, and S. K. LeeSeoul National University Hospital, Seoul, Korea

Purpose: We tried to evaluate the long-term efficacy and safety of Ox-carbazepine (OCB) and Levetiracetam (LEV) treatment as monotherapyin the tertiary epilepsy center on broad population.

Method: All patients who had been treated with LEV or OCB as mono-therapy at Seoul National University Hospital from 2007 to March 2009were recruited. The patients who had brain surgery for seizure control orwho associated dynamic disease were excluded. Electronic medicalrecords were retrospectively reviewed. Efficacy was measured using afive point scale. Adverse events were also recorded. Retention rates werecalculated using life-table method.

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Result: Total 184 patients with OCB were recruited, including 137(89.1%) localization related epilepsy patients. Of total 188 patients withLEV, 127 (62.8%) patients were localization related epilepsy. Meanduration of follow up in group of OCB (67.4 month) was longer than ingroup of LEV (22.3 month). The seizure free rate in OCB and LEV was53.3% and 61.7%. Tolerance in OCB was significantly higher than withLEV (21.7% versus 8.5%, P<0.001). Dose of LEV was inversely corre-lated with seizure free outcome and tolerance. The retention rates at3-year were 78% in group of OCB and 75% in LEV. The incidence ofadverse events of OCB was significantly higher than LEV (41.3% versus24.5%, p<0.001). However, the incidence of irritability was higher in thepatients with LEV (13.8%) than in OCB (3.8%).

Conclusion: Oxcarbazepine and levetiracetam was effective and safe onmonotherapy and the retention rates were well maintained up to threeyears.

p184GENERIC SUBSTITUTION OF ANTIEPILEPTIC DRUGS– A SURVEY OF THE PATIENT'S PERSPECTIVEK. Hensler*, C. Uhlmann�, T. Porschen�, R. Benecke*, andJ. Rçsche**Universittsmedizin Rostock, Rostock, Germany; �

S�dw�rttembergisches Zentrum f�r Psychiatrie, Weissenau,Germany; and �Landesverband f�r Epilepsie SelbsthilfeNordrhein-Westfalen e.V., Kçln, Germany

Purpose: In this study we tried to determine the patient's attitudes togeneric substitution of antiepileptic drugs (AEDs) and their experienceswith the usage of generic antiepileptic drugs in Germany and other Ger-man speaking countries.

Method: In April 2011 2000 copies of a 25-item questionnaire weredelivered with a magazine edited by a patient's organisation. Each itemconsisted of a 5-point Likert scale. Additionally the questionnaire wasplaced on the internet platform of another patient's organisation fromMay to September 2011. We calculated Spearman correlation coeffi-cients between the answers in different items.

Result: When responses of relatives and of patients, who could notdetermine whether they had experiences with generic AEDs or not, wereexcluded, 99 paper questionnaires and 128 internet questionnaires couldbe analysed. 95% of the patients (128 female, 99 male) were from Ger-many. 112 (= 49%) patients reported experiences with generic substitu-tion of AEDs. 34% of them complained about difficulties with thegeneric substitution (Likert scale 4 or 5) and 25.5% had a breakthroughseizure (Likert scale 4 or 5). 9.6% of the patients admitted complianceproblems after generic substitution (Likert scale 4 or 5). Complianceproblems were correlated with breakthrough seizures (r = 0.48, p <0.001).

Conclusion: A considerable amount of patients experiences break-through seizures after generic substitution of AEDs. The percentage ofbreakthrough seizures in our study is in line with results from earlier sur-veys in English speaking countries. Compliance problems may be theresult or in some cases the cause of breakthrough seizures.

p185TOPIRAMTE AND DYSKINESIAY. Liang*, H. Tsai�, and C. Lo**National Chen Kung University Hospital, Douliou branch,Yulin, Taiwan; and �Chiayi Christian Hospital, Chiayi, Taiwan

Purpose: Topiramate is a sulfamate substituted monosaccharide. It actsto reduce voltage gated sodium channels and also enhances postsynapticGABA-receptor currents and limits activation of the AMPA-kainate

types of glutamate receptors. Recently, besides acting as an antiepilepticdrug, it is also being investigated as a candidate in treating periodic limbmovement disorder (PLMD). Here we report a case that has excellentresponse to topiramate in controlling PLMD, but later developed tardivedyskinesia involving jaw and tongue.

Method: The detail medical history, clinical presentation, and responsesto medications (including madopar, rivotirl, topiramate) of this patientwere reviewed and summarized. The pathogenesis of PLMD, the mecha-nism of topiramate in controlling PLMD, a comparison with other medi-cations, and a hypothesis in how topiramate might induce tardivedyskinesia are discussed.

Result: Madopar and rivotril did not show any effect in controllingPLMD and later on the dyskinesia. Topiramate stopped the PLMD com-pletely, however is suspected to have caused dyskinesia.

Conclusion: While the mechanism of topiramate in controlling epi-lepsy, and the underlying pathogenesis of PLMD are not entirely under-stood, our case report might help in understanding both by providingevidence that ion channels and receptors may play a role.

Neuroimaging and Neurophysiology 1Monday, 01 October 2012

p186ICTAL [99MTC] HMPAO SPECT IN NONLESIONAL EX-TRATEMPORAL EPILEPSYE. Pataraia, S. Aull-Watschinger, R. Jung, T. Traub-Weidinger,and S. Asenbaum-NanMedical University Vienna, Vienna, Austria

Purpose: Ictal SPECT has been applied successfully in temporal lobeepilepsy (TLE) to localize the seizure onset zone with high sensitivity,especially in mesial TLE. The sensitivity of ictal SPECT is significantlylower in extratemporal lobe epilepsies (ETLE). The delineation of theepileptogenic zone in patients with non-lesional ETLE is the major chal-lenge in epileptology. The aim of the present study was to evaluate theclinical benefit of ictal SPECT in non-lesional extratemporal epilepsy(ETLE).

Method: The patients with suspected non-lesional ETLE (non-localiz-ing or discordant non-invasive data during the prolonged Video-EEG-Monitoring and negative MRI) were subjected to ictal SPECT studies forplanning invasive monitoring or surgery strategy. Ictal SPECT was con-sidered to be useful for decision-making if it obviated the need for inva-sive monitoring or influenced its planning.

Result: Ictal [99mTc] SPECT results of 25 patients (14 men, 11 women)with suspected non-lesional ETLE (mean age 32.68€9.6 years) wereincluded in final analysis. The time from clinical onset of seizure andinjection was from 6 to 38 sec (mean 13.28€9.07 sec). The patients weredivided into two groups: those where the non-invasive evaluation pre-sumed a seizure onset zone in one region (localizable), and those wherethe seizure onset zone was not lateralizable or localizable (non-localiz-able). Ictal SPECT was decided to be successful if it provided any addi-tional information in regard to localization of epileptogenic zone. In 6 of14 patients (43%) of localizable group ictal SPECT provided additionalinformation, whereas only in 1 of 11 patients (9%) of non-localizablegroup ictal SPECT was helpful in decision-making and planning theinvasive recordings (p=0.07). Additionally in 17 patients [18F] FDG and/or [11C] FMZ PET were available. FDG and FMZ did not demonstrateany abnormalities except in one patient.

Conclusion: Ictal SPECT provided more localizing information andinfluenced the final decision-making only in patients were based on the

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non-invasive monitoring results the seizure onset zone could be localizedto one region of the brain. In opposite to TLE clinical benefit of ictalSPECT preoperatively in non-lesional ETLE seems to be limited. Due torapid changes of perfusion state peri-ictally (for example due to rapid sei-zure spread especially in frontal lobe epilepsy) successful ictal SPECTinvestigations might lack clinical benefit with respect to possible surgicalinterventions. These findings need to be validated in a larger group ofpatients. The subtraction with interictal SPECT would also improve theseresults.

p187MAGNETOENCEPHALOGRAPHIC MEASURES OFABNORMAL SENSORY OSCILLATIONS: A WINDOWON PHOTOSENSITIVE EPILEPSYG. Perry*, L. M. Brindley*, S. M. Muthukumaraswamy*,K. Hamandi�, and K. D. Singh**Cardiff University, Cardiff, UK; and �University Hospital ofWales, Cardiff, UK

Purpose: Photosensitivity is a common trait in a number of epilepsysyndromes. Measuring visual responses with magnetoencephalography(MEG) provides a unique opportunity for the non-invasive study ofabnormal cortical oscillations in these patients. Evidence points to photo-sensitivity being due to abnormalities in cortical inhibition, and this maybe reflected in oscillations in the gamma frequency range (30–100Hz),which are believed to reflect GABAergic inhibitory processes. The pur-pose of the present study was to use MEG to identify differences in theseoscillations between photosensitive patients and non-photosensitive con-trols.

Method: Data were collected from ten patients with photosensitive epi-lepsy and two age-matched control groups. Participants underwent MEGrecording while viewing static visual gratings. Responses were localisedto the visual cortex and the relationship between visually-induced oscilla-tions and stimulus parameters (contrast and size) were compared betweenthe different participant groups.

Result: Contrary to our expectations, we did not find clear evidence fora difference between groups in the main gamma-band response (40–70Hz). Instead our results suggest differences at a lower frequencyaround 28Hz, and in the alpha frequency (8–12Hz) range.

Conclusion: Our evidence suggests that there may indeed be character-istic differences in visually-induced oscillations between individualswith photosensitive epilepsy and controls, which may have potential useas diagnostic markers. The finding of differences in the high beta/lowgamma and alpha frequency ranges suggests that pathophysiological dis-turbances may be localised to thalamo-cortical processes, and thus ourdata could guide future research into the mechanisms of seizure genera-tion in photosensitive epilepsy.

p188COMPARISON OF EEG-FMRI DATA TO INVASIVEELECTROPHYSIOLOGICAL REGISTRATION INCRYPTOGENIC FOCAL EPILEPSYI. Pesaresi*, S. Fabbri�, C. Barba�, E. Bartolini§, P. Cecchi�,F. Giordano�, F. M. Quaglia�, D. Pruna–, M. Cosottini�, andR. Guerrini�

*AOUP, Pisa, Italy; �Pisa University, Pisa, Italy; �Children'sHospital Meyer, Florence, Italy; §Pisa University, Pisa, Italy;and –Azienda Ospedaliero Universitaria of Cagliari, Cagliari,Italy

Purpose: To compare different methodological approaches in a patientwith cryptogenic epilepsy who underwent invasive neurophysiologicinvestigation.

Method: A 15 year old boy with drug-resistant cryptogenic epilepsyunderwent continuous EEG- fMRI acquisition using a 3T MR scanner.During the examination 26 interictal electric abnormalities were regis-tered. The fMRI data analysis was performed by different event-related(ER) design adopting respectively canonical hemodynamic responsefunction (HRF), Fourier and Finite Impulse Response (FIR) basis func-tions. The localization of activation/deactivation clusters obtained byeach statistical approach was compared with the localization of the ‘‘sei-zure onset zone’’ obtained by invasive stereo-EEG.

Result: Similar activation maps were obtained by ER design using FIRbasis functions and Fourier basis functions as HRF. Both approaches pro-vided clusters of activation concordant with the ‘‘seizure-onset’’ zoneidentified by depth electrodes. On the other hand, ER design combinedwith standard HRF was not able to identify clusters within the ‘‘seizure-onset’’ zone.

Conclusion: The ER approach using Fourier and FIR basis functionsmight provide adjunctive information with respect to standard HRF. Therole of non-canonical approaches in identifying the epileptogenic zoneneeds to be evaluated on large series of patients.

p189STRESS AFFECTS EMOTIONAL PROCESSING IN LEFTTEMPORAL LOBE EPILEPSYJ. Szaflarski, J. Allendorfer, H. Heyse, and L. MendozaUniversity of Cincinnati Academic Health Center, Cincinnati,OH, USA

Purpose: To assess how stress (S) affects emotion processing in patientswith left temporal lobe epilepsy (LTLE).

Method: Included were 22 LTLE patients who believed (+S; n=15) anddid not believe (-S; n=7) that stress played a role in their seizure control.Subjects were presented a pseudo-randomized series of faces with differ-ent expressions (happy/fearful/sad/neutral) during fMRI and instructed topress 1 for male and 2 for female face. After scanning, subjects wereasked to indicate the expression on each of the previously presentedfaces; fMRI analysis only included correctly rated faces. FMRI imagecoregistration, spatial normalization, single-subject and group statisticalmodeling, and visualization were performed using AFNI. Single-subjectfMRI response to emotion was determined using general linear modeling(happy, fearful, or sad faces contrasted with neutral faces). Group differ-ences in neural processing of each emotion were performed using 2-sam-ple t-tests (p<0.05, cluster threshold of 20 voxels).

Result: Overall accuracy on post-scan rating of faces was better for -Sthan +S (p=0.012); the +S showed overall greater involvement of the pre-frontal and medial temporal/amygdala regions. The groups also showeddifferential patterns of activation for each emotion (fear/sadness/happi-ness). Compared with -S, +S exhibited diminished response particularlyin superior frontal regions when processing fear and sadness, butincreased response in left temporal regions when processing happiness.

Conclusion: Patients who do and do not believe that stress affects theirseizure control recruit different brain regions during emotional process-ing; this difference may underlie the decreased accuracy of +S patients inrating emotional faces.

(Support: Shor Foundation for Epilepsy Research).

p190IDENTIFICATION OF THE EPILEPTOGENIC ZONE BYEEG-FMRI: CONCORDANCE BETWEEN PRE-SURGI-CAL EEG-FMRI AND SUBSEQUENT STEREO-EEGDATAL. Mirandola*, M. Pugnaghi*, F. Benuzzi*, P. Avanzini�,G. Cantalupo�, G. Lo Russo�, L. Tassi�, and S. Meletti*

56

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*University of Modena and Reggio Emilia, Modena, Italy; �

University of Parma, Parma, Italy; and �Ospedale Niguarda-Ca’ Grande, Milano, Italy

Purpose: To illustrate a paradigmatic case of concordance between pre-surgical EEG-fMRI and subsequent Stereo-EEG data.

Method: We report the case of a 27 year-old left-handed man, whounderwent epilepsy surgery after an extensive pre-operatory investiga-tion. Epilepsy started at age of 5 months. Staring, flushing, and biman-ual automatisms characterized his drug-resistant partial seizures. Thepatient underwent prolonged Video-EEG recordings and two EEG-fMRI studies, both performed with subsequent Independent Compo-nent Analysis (ICA) on EEG data. He also performed an intracranialmonitoring.

Result: Scalp EEG revealed bilateral frontal interictal paroxysmalabnormalities, while prolonged video-EEG recordings showed a leftfronto-temporal localization of ictal events. Different interictal spikesdataset (ISD) were recorded during the first EEG-fMRI study and twodistinct cluster of BOLD signal increase were identified: one locatedin the left frontal pole and the other in the ipsilateral dorso-lateralfrontal cortex. Structural brain MRI revealed thickening and blurringof the fronto-polar cortex suggesting the presence of a focal corticaldysplasia and a tailored cortectomy involving the fronto-polar regionwas then performed. After three-months seizure-free period the patientexperienced seizures recurrence. Post-operative EEG-fMRI, with therecording of ISD and one ictal event, and intracranial EEG results withthe recording of several seizures, confirmed the involvement of thedorso-lateral frontal cortex, spared by the first cortectomy. In conclu-sion this data show how EEG-fMRI could identify the epileptogeniczone as demonstrated by concordance with Stereo-EEG results andclinical outcome. It represents a promising tool that should be imple-mented in the diagnostic work-up of patients with surgically-remedia-ble epilepsies.

p191UNVEILING THE MYSTERY OF D�J� VUM. Brazdil*, R. Marecek�, T. Urbanek�, T. Kasparek§, M. Mikl�,I. Rektor*, and A. Zeman–

*Brno Epilepsy Center, Brno, Czech Republic; �CEITEC MU,Brno, Czech Republic; �Academy of Sciences of the CzechRepublic, Brno, Czech Republic; §Masaryk University, Brno,Czech Republic; and –University of Exeter, Exeter, UK

Purpose: D�j� vu is an eerie experience that is characterized by the rec-ognition of a situation concurrent with the awareness that this recognitionis inappropriate. This feeling of irrelevant familiarity is a common phe-nomenon occurring both in clinical (mainly epileptic) and nonclinicalpopulation. Despite numerous theories have been suggested as to whatnonpathological d�j� vu is and what causes it, until now no ultimateexplanation has been generally accepted.

Method: We investigated differences in brain morphology betweenhealthy subjects with and without d�j� vu using a novel multivariate neu-roimaging technique, Source-Based Morphometry.

Result: The analysis revealed a set of cortical (predominantly me-siotemporal) and subcortical regions in which there was significantlyless gray matter in subjects reporting d�j� vu. In these regionsgray matter volume was inversely correlated with the frequency ofd�j� vu.

Conclusion: Our results demonstrate for the first time a structural corre-late of d�j� vu in healthy individuals and implicate a direct pathogeneticlink between nonpathological and epileptic d�j� vu. We hypothesize ourfindings reflect an alteration of hippocampal function and postnatal neu-rogenesis in subjects with d�j� vu.

p192HOW TO IMPROVE THE YIELD OF FDG-PET IN THEPREOPERATIVE WORK-UP FOR EPILEPSY SURGERYM. A. Van ‘T Klooster*, F. S. S. Leijten*, G. J. M. Huiskamp*,R. M. C. Debets�, E. F. I. Comans�, S. Bouvard§, and P. Ryvlin–

*UMC Utrecht, Utrecht, The Netherlands; �2 Epilepsy Instituteof The Netherlands Foundation (SEIN), Heemstede, TheNetherlands; �VU University Medical Center, Amsterdam, TheNetherlands; §CERMEP—Imagerie du Vivant, Lyon, France;and –Institute for Child and Adolescent with Epilepsy (IDEE),Hospices Civils de Lyon, Lyon, France

Purpose: Fluorodeoxyglucose PET (FDG-PET) is a costly, semi-inva-sive, interictal method to localize epileptogenic foci, marked bydecreased FDG uptake. Since PET facilities and experienced reviewersare scarce we investigated how to improve the yield of the preoperativeFDG-PET scan. We, retrospectively, compared three FDG-PET assess-ments to ictal electrocorticography (ECoG): initial clinical visual assess-ment (PETclin), blinded visual re-assessment (PETre) and StatisticalParametric Mapping (SPM) analysis (PETspm).

Method: 44 Refractory focal epilepsy patients (mean age 25y, 19female, 75% extra-TLE) who underwent chronic ECoG monitoring wereincluded. All patients and 38 healthy controls underwent a static FDG-PET scan (ECAT EXACT HR+). PETclin reports were collected. PETre

was executed by the same two experts as for PETclin. Thirdly, PETspm

was performed; each patient scan was compared, at cluster level(puncorr<0.001), to the healthy controls. The ictal ECoG electrodes wereco-localized. Results were classified into ten predefined brain anatomicalregions, and analysed on group (kappa, sensitivity, specificity) andpatient level.

Result: The number of scans without abnormalities for PETclin, PETre

and PETspm were 5, 1 and 0, respectively, without overlap. Preliminaryresults indicate that PETre increases the overall sensitivity compared toPETclin, maintaining equal specificity. On patient level PETspm revealsnew results in case of normal PETclin, or additional information regardingthe focus.

Conclusion: Visual re-assessment should be considered when initialassessment is negative. We advise to use more than one method whenjudging a FDG-PET scan in these types of difficult patients since re-eval-uation has the potential to increase epilepsy surgery eligibility.

p193MULTIMODAL EVOKED POTENTIALS BE USEFULTOOL IN THE STUDY OF ENCHEPHALOPATY WITHSTATUS EPILEPTICUS DURING SLOW SLEEP –REPORT 5 CASESP. A. Ruiz, J. J. Ortega, J. R. Diaz, A. D. Ghinea, E. Canovas,and J. M. PinzonHospital General De Castellon, Castellon De La Plana, Spain

Purpose: Encephalopathy with status epilepticus during sleep is charac-terized by severe impairment of neuropsychological development, char-acteristic EEG pattern of continuous spike-wave during slow sleep andseizures in children. We appreciate the usefulness of Multimodal EvokedPotentials in the diagnosis and evolution of this disorder.

Method: We studied 5 children (mean 7 years old) with ESES withsevere developmental deficit and few seizures; we performed a Poly-somnogram, Neuropsychological Development Test and Visual-EvokedPotentials, Somatosensory-Evoked Potential and Cortical and BrainstemAuditory-Evoked Potential. Only in cases found altered evoked poten-tials, we make annual checks, followed until the continuous spike-wave

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pattern during sleep was resolved. Normal values were taken from agroup of healthy children (3–13 years).

Result: Four cases showed a rate spike-wave in slow sleep > 85% andseizures. Three cases, showed behavior disorders and severe deteriora-tion in the language area. Find a delay P100 wave in VEP of two caseswith significant visual deficit. PEAC was altered in a case with AuditoryVerbal Agnosia, showing normal BAEP; and SSEP was normal in allcases. These alterations disappear at the same time it solves the continu-ous spike-wave pattern of sleep EEG.

Conclusion: EPs have been studied as diagnostic evidence for epilepsy,but there are few data on the usefulness of Multimodal Evoked Potentialsin children with ESES. The close relation between changes in EP and theEEG is very important redefine which neuro-behavioral areas would beinvolved in patients with this encephalopathy, being useful in the diagno-sis and evolution.

p194MESIAL TEMPORAL SCLEROSIS WITH MRI SIGNALSEXTENDING TO THE FORNIXS. Baz*, A. Alsemari�, and F. Almuhailib�

*KFSHRC, Riyadh PO Box 3354, Saudi Arabia; and �KingFaisal Specialist Hospital & Research Centr, PO Box 3354,Saudi Arabia

Purpose: Mesial temporal sclerosis had been reported with ipsilateralfornix atrophy, however the extension of the MRI signals to the fornix isseldom reported.

Method: To demonstrate the clinical, electrophyological and the imag-ing data of the findings.

Result: 39 years old lady with refractory left temporal lobe epilepsysince adolescent on multiple anti-epileptics admitted to epilepsy moni-toring unit for surgical evaluation. 5 seizures were captured at differentinterval then MRI was arranged several days after the last seizures. Itshowed mesial temporal sclerosis but with minor swelling of mesialtemporal structures and a significant signal intensity and swelling ofthe fornix. The patients had slightly bigger sized fornix and mesialtemporal structures several days after repeated seizures. However theprevious MRI brain few years earlier demonstrated thin asymmetricleft fornix.

Conclusion: Recurrent seizures may influence the apparent thickness ofthe fornix however other possibilities may be entertained as neoplasticinfiltration or inflammatory process.

p195LOCALIZING EPILEPTIC NETWORKS IN TUBEROUSSCLEROSIS USING ARTERIAL SPIN LABELING MRIPERFUSIONA. Azarion, and K. A. DavisHospital of the Univeristy of Pennsylvania/University ofPennsylvania School of Medicine, 4127829, USA

Purpose: The goal of this study is to utilize the noninvasive technique ofarterial spin labeling (ASL) magnetic resonance imaging (MRI) to iden-tify epileptic networks in patients with tuberous sclerosis complex(TSC), a subtype of neocortical epilepsy. Given that patients with TSCoften have better seizure control after surgical resection of epilepticlesions as well as the neighboring perilesional tissue, this cohort is idealfor testing the hypothesis that ASL can accurately identify epilepticnetworks. Recent studies have shown that the quantitative ASL signal

correlates with underlying pathological changes of tubers, as well as theirepileptic potential.

Method: In this study we plan to analyze the perfusion patterns bothwithin tubers and in the surrounding perilesional regions in two popula-tions of TSC patients, those with epilepsy (6 patients), and those with nohistory of seizures (6 patients). Epileptic tubers will be cross-identifiedwith scalp EEG, and this data will be correlated with ASL perfusionmaps.

Result: We have obtained and analyzed ASL and MRI data on 4 TSCpatients with epilepsy. Thus far, it appears that epileptic tubers and sur-rounding perilesional areas show hyperperfusion in comparison withaverage cerebral blood flow. Analysis of the nonepileptic tubers revealsno significant differences in perfusion compared to average cerebralblood flow.

Conclusion: Our preliminary data shows that ASL can accurately iden-tify epileptic networks in TSC. Using ASL to identify epileptic networkscan be potentially applied to all patients with neocortical epilepsy, withthe ultimate goal of improving seizure freedom rates from resectivesurgery.


p196THE EFFECT OF GENERALIZED SPIKE AND WAVESDISCHARGE DURATION AND IGE SUB-SYNDROMEON BRAIN NETWORKS AS REVEALED BY EEG-FMRIM. Pugnaghi*, D. W. Carmichael�, A. Vaudano�,U. J. Chaudhary§, F. Benuzzi*, C. Di Bonaventura�,A. T. Giallonardo�, R. Rodionov§, M. C. Walker–, J. Duncan§,S. Meletti*, and L. Lemieux§

*University of Modena and Reggio Emilia, Modena, Italy; �UCLInstitute of Child Health, London, UK; �University of Rome ‘‘LaSapienza’’, Rome, Italy; §UCL Institute of Neurology, London,UK; and –Department of Clinical and Experimental Epilepsy,London, UK

Purpose: To investigate the hemodynamic correlate of generalizedspike wave discharges (GSWD) duration and in particular the relation-ship between discharge duration and the magnitude and extent of theBOLD changes.

Method: We studied 42 adult patients with Idiopathic Generalized Epi-lepsies (IGE) who underwent simultaneous recordings of EEG and func-tional MRI (EEG-fMRI) in three centres (London, UK; Modena andRome, Italy). We applied a parametric analysis at the single subject levelin order to explore the presence of non-linear effects of duration ofGSWD on the BOLD changes. A full-factorial ANOVA design was per-formed as a random effect group analysis to model possible effects ofIGE sub-syndrome and different MRI scanners.

Result: The group analysis of the GSWD linear effect revealed BOLDsignal changes in a network of brain regions: mainly transient BOLDincreases in the thalami and bilateral insulae, and transient BOLDdecreases in the posterior cingulate, precuneus and bilateral parietalregions. No significant non-linear effect of GSWD duration on BOLDwas found. The full-factorial ANOVA analysis disclosed no main effectof the MRI scanner across the three centres, and no main effect of thesub-syndrome.

Conclusion: Our findings support the idea that the amplitude ofthe BOLD response is linearly related to the GSWD duration with no

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non-linear (or threshold) effect of duration. These results do not supportthe existence of a critical GSWD duration underlying consciousnessimpairment.

p197SPECT PERFUSION PATTERNS IN PAEDIATRIC EPI-LEPSY OF TEMPORAL LOBE ORIGIN – CORRELA-TION WITH SURGICAL OUTCOMEP. S. Lakkunta*, S. J. Sattaluri�, and M. Panigrahi�

*Krishna Institute Of Medical Sciences, Secunderabad, India;and �Cecunderabad, India

Purpose: To assess the role of ictal SPECT in paediatric Temporal lobeepilepsy (TLE) and to correlate Ictal perfusion patterns with Surgical out-come.

Method: A retrospective analysis of Ictal & Interictal SPECT, IctalVideo EEG, MRI and surgical outcome was performed in 27children ofTLE. SPECT Perfusion patterns were classified as Typical (anteromedi-al, anterolateral, inferior) and Atypical (extra temporal). Surgical out-come was assessed according to Engel's classification.

Result: Ictal and Interictal SPECT were done in 21, Interictal alone in 6.Sixteen had Hippocampal sclerosis (HS), while nonHS group had neuro-nal loss in four, Dual pathology in two, FCD in 2, ganglioglioma in 1, gli-osis in one and normal in one . Sensitivity of ictal SPECT is 95%,interictal is 78%. SPECT was diagnostic in 85.7% of normal MRIpatients. Typical pattern with anteromedial and lateral hyperperfusion iscommonest in HS (75%). Atypical pattern is more commonly seen innonHS group than with HS (45.4% vs 25%). 91.6% of HS group with typ-ical pattern are in Engel's class 1 outcome. Whereas 80% of nonHS groupwith atypical pattern are in poor surgical outcome (p < 0.05).

Conclusion: Ictal SPECT is highly sensitive (95%) in pre surgical eval-uation of paediatric TLE. Typical pattern is commonest in HS (75%) andshows good surgical outcome. Significant association of atypical patternwith poor surgical outcome is noted in nonHS group (p value<0.05).

p198FUNCTIONAL CONNECTIVITY STUDY IN PATIENTSWITH TEMPORAL LOBE EPILEPSY AND DEPRESSIVESYMPTOMSR. Rocamora*, N. Roe-Vellve�, R. M. Vivanco-Hidalgo*,M. Picado�, B. Villoria*, A. Merino*, C. Garcia-Ribera*,A. Bulbena*, and O. Vilarroya�

*Parc de Salut Mar-Hospital de Mar, Barcelona, Spain; and �

Fundacio IMIM, Barcelona, Spain

Purpose: Our objective is the evaluation and characterization of neuro-functional, psychopathologic and neuropsychologic abnormalities pres-ent in a group of 15 TLE patients and 15 healthy controls.

Method: We obtained fMRI scans from all participants and performedresting state analyses based on ROIs in order to study markers associatedwith abnormalities in functional connectivity relate to mood alterations.

Result: Our preliminary results indicate hyperactivation in right anteriorcingulate cortex (ACC), bilateral thalamus and insula; and hypoactiva-tion in the left amygdala in the TLE patients as compared with the controlgroup. We also performed a-priori ROIs of thalamic and ACC regions,which previous studies relate with depression. We found increased acti-vation in such areas correlated with depression symptoms severity.

Conclusion: Our results indicate the presence of neurofunctional differ-ences in TLE patients that might be due to shared neural pathophysiologi-cal abnormalities underlying both epilepsy and depression, and mightexplain the presence of mood alterations in epilepsy.

p199CONVERGENT EVIDENCE OF REGIONAL THALAMICABNORMALITIES IN MESIAL TEMPORAL LOBE EPI-LEPSYS. S. Keller, C. Traynor, J. O’Muircheartaigh, G. J. Barker,W. Crum, and M. P. RichardsonKing's College London, London, UK

Purpose: Multiple MRI studies have revealed global thalamic atrophyin human mesial temporal lobe epilepsy (mTLE). In animal limbic epi-lepsy, the medial nuclei of the thalami have been described as the consis-tent neuroanatomical alteration (Bertram et al., 2001, Epilepsia; 42:967).Using MRI and DTI, we sought to investigate the topology of intra-tha-lamic alterations in mTLE.

Method: For 12 patients with mTLE and 18 healthy controls, weacquired DESPOT structural sequences for T1 and T2 mapping of sixthalamic sub-regions per hemisphere based on a previously describedprotocol (Traynor et al., 2011, Neuroimage; 56:939) and DTI sequencesfor connectivity-based segmentation of the thalamus (Behrens et al.,2003, Nat Neurosci; 6:750) using a 3 T GE system. T1/T2 thalamic mapsused the work of Morel et al. (1997, J Comp Neurol; 387:588) for ana-tomical reference.

Result: Left (p=0.03) and right (p=0.02) Region 5 (including anteroven-tral, anteromedial, and ventral lateral posterior nuclei), and right(p=0.01) Region 3 (including medial pulvinar, mediodorsal and centrallateral nuclei) were significantly reduced in volume in patients relative tocontrols. Furthermore, right Region 3 had significantly greater T2 valuesin patients (p=0.01). From connectivity-based segmentation, the thalamicsub-region classified as connecting to the right temporal target regionwas significantly smaller in patients (p=0.05).

Conclusion: Thalamic sub-regions known to connect with the hippo-campus are architecturally altered in mTLE. These thalamic regions mayrepresent a central hub for the propagation and synchronisation of tempo-ral lobe seizures, mediating the spread of hippocampal epileptiformactivity to neocortex.

p200MR IMAGING IN STATUS EPILEPTICUS SECONDARYTO PARANEOPLASTIC ENCEPHALITISS. Sarria, M. Toledo, C. Lorenzo I Bosquet, E. Lainez,S. Siurana, C. Auger, E. Santamarina, X. Salas-Puig, R. Mitjana,C. Vert, L. Fraschieri, and A. RoviraVall d¢Hebron University Hospital, Barcelona, Spain

Purpose: Patients with systemic cancer may have new-onset status epi-lepticus (SE) as the main clinical feature of paraneoplastic encephalitis.Five such patients who underwent MRI during SE or immediately afterrecovery are described.

Method: We retrospectively reviewed the MR scans of five consecutivepatients who experienced SE as the onset of paraneoplastic encephalitisbetween January)2005 and July-2011. All patients met the criteria forparaneoplastic syndrome. Three patients had small-cell lung carcinoma,two of them with anti-Hu antibodies. The two remaining patients hadintestinal and lung adenocarcinoma. The SE episode was convulsive intwo patients and none-convulsive in three patients.

Result: All patients showed hyperintense lesions on T2-weightedimages involving the limbic structures, specifically the hippocampus.Three patients additionally had scattered extralimbic areas of high-signalintensity. The T2 hyperintensities were related to the electroclinical onsetof the seizures. Perfusion MRI obtained with arterial spin labeling (ASL)in one patient showed hyperperfusion overlapping the inflammatorylesions. SPECT and PET performed in 4 patients demonstrated increasedmetabolism limited to the areas of encephalitis. Mild to moderate contrast

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enhancement was seen in only one patient. In images performed follow-ing recovery, atrophy of the affected hippocampus was observed. In twopatients who had recurrent paraneoplastic encephalitis manifesting asSE, new T2 lesions with a different topography were detected.

Conclusion: Limbic and extralimbic encephalitis can be secondary toparaneoplastic syndrome in new-onset SE. MR study shows consistentlyhyperintense lesions on T2-weighted imaging, sometimes with mild con-trast enhancement, and increased perfusion or metabolism as demon-strated by ASL or PET/SPECT.

p201DYNAMIC EFFECTIVE CONNECTIVITY OF EPILEP-TIC NETWORKS DETERMINED WITH HIGH DENSITYEEG SOURCE ANALYSISS. Vulliemoz*, R. Tyrand�, L. Astolfi�, B. He§, M. Seeck*,C. Michel*, and G. Plomp�

*University Hospital of Geneva, Geneva, Switzerland; �

University of Geneva, Geneva, Switzerland; �La SapienzaUniversity, Roma, Italy; and §University of Minnesota,Minneapolis, USA

Purpose: Analyzing the dynamic behaviour of epileptic networks couldhelp to better understand the way pathologic neural activity propagates,and leads to spikes, seizures, and their electro-clinical and cognitive man-ifestations, with implications for epilepsy surgery candidates.

Method: In 6 patients with temporal lobe epilepsy we studied effectiveconnectivity of large-scale cortical networks at high temporal resolutionaround interictal spikes, recorded with high density (256 channels) EEG.The cortical electric source activity was obtained for 90 cortical regionsof interest (ROI) using a distributed inverse solution. Multivariate, time-varying (millisecond resolution), and frequency-resolved (1–50Hz)Granger causality analysis (Partial Directed Coherence) was applied tothe source signal for all ROIs. In all patients subsequent intracranialrecording or surgical resection was used for validation.

Result: Information flow occurred predominantly in the theta and betabands. The key driving structures where located in the anterior and med-ial temporal regions, with peak information transfer before the spikemaximum. We found fast-varying connectivity patterns between the an-tero-medial and lateral temporal lobe and basal frontal lobe, but also tran-sient transfer towards the contralateral temporal lobe. In two patientswith a multifocal irritative zone, we found evidence of connectivity fromthe main anterior temporal driver towards the secondary spike focusremote from the epileptogenic zone.

Conclusion: EEG-based time-varying effective connectivity of epilep-tic spikes provides a clear characterization of the epileptic networks thatis concordant with invasive electro-clinical findings. This could havemajor clinical implications for tailoring resective, disconnective, andfunctional surgery.

p202ALTERED RESTING-STATE CONNECTIVITY DURINGINTERICTAL GENERALIZED SPIKE-WAVE DIS-CHARGES IN DRUG-NA�VE CHILDHOOD ABSENCEEPILEPSYT. Yang, C. Luo, Q. Gong, and D. ZhouWest China Hospital, Sichuan University, Chengdu, China

Purpose: To investigate the intrinsic brain connections at the time of in-terictal generalized spike-wave discharges (GSWDs) to understand theirmechanism of effect on brain function in untreated childhood absenceepilepsy (CAE).

Method: The EEG-functional MRI (fMRI) was used to measure theresting state functional connectivity during interictal GSWDs in drug-naıve CAE, and three different brain networks—the default mode net-work (DMN), cognitive control network (CCN), and affective network(AN)—were investigated.

Result: Cross-correlation functional connectivity analysis with prioriseed revealed decreased functional connectivity within each of thesethree networks in the CAE patients during interictal GSWDS. Itincluded precuneus-dorsolateral prefrontal cortex (DLPFC), dorsome-dial prefrontal cortex (DMPFC), and inferior parietal lobule in theDMN; DLPFC-inferior frontal junction (IFJ), and pre-supplementarymotor area (pre-SMA) subregions connectivity disruption in CCN;ACC-ventrolateral prefrontal cortex (VLPFC) and DMPFC in AN;There were also some regions, primarily the parahippcampus, paracen-tral in AN, and the left frontal mid orb in the CCN, which showedincreased connectivity.

Conclusion: The current findings demonstrate significant alterations ofresting-state networks in drug naıve CAE subjects during interictalGSWDs and interictal GSWDs can cause dysfunction in specific net-works important for psychosocial function. Impairment of these networksmay cause deficits both during and between seizures. Our study may con-tribute to the understanding of neuro-pathophysiological mechanism ofpsychosocial function impairments in patients with CAE.

p203COMPARISON OF FDG-PET AND ICTAL SPECT INCHILDREN WITH FOCAL EPILEPSY UNDERGOINGPRE-SURGICAL EVALUATIONN. Vora*, V. I. Venegas�, L. Biassoni�, H. Cross§, andC. M. Eltze–

*Lilavati Child Neuro Care, Ahmedabad, India; �ClinicaAlemana Santiago, Las Condes Santiago de Chile, Chile; �GreatOrmond Street Hospital for Children, London, UK; §UCL-Institute of Child Health, London, UK; and –University CollegeLondon, Institute of Child Health, London, UK

Purpose: Ictal SPECT and fluorodeoxyglucose (FDG) - PET provideadditional information to localise the epileptogenic zone especially whenmagnetic resonance imaging (MRI) is negative. Requirements for video-EEG and tracer injection close to seizure-onset pose logistic difficultiesthat may limit usefulness of ictal SPECT in pre-surgical evaluation. Herewe compare the yield of ictal SPECT and FDG-PET in children withfocal epilepsy undergoing pre-surgical evaluation.

Method: Children evaluated in the supra-regional epilepsy surgery pro-gram who underwent both ictal SPECT and FDG-PET were identified.Reports issued by the program radiologist were analyzed. Additionalclinical information was obtained from patient's records.

Result: 24 children (14 males, mean age of seizure onset 3.5 years, sd+/)3.4) were identified, of which MRI was negative in 18 (75%). IctalEEG was focal in 13 (54%) cases, concordant with FDG-PET in 5 andSPECT in 6. FDG-PET provided localising information in 17 (71%) andSPECT in 14 (58%) cases with concordance of both in 10 (42%). In 7children with focal FDG-PET changes, ictal SPECT was not localising (5multifocal/bilateral, 2 negative), whilst SPECT indicated a focal lesion in4 with non-localising FDG-PET (2 multifocal/bilateral, 2 negative).Surgery was offered to 11 children (45%).

Conclusion: FDG-PET provided additional localising information ina large proportion of mostly MRI negative patients justifying selec-tive utilisation of Ictal SPECT. The high proportion of discordanceof both imaging modalities emphasises the importance of a multidis-ciplinary approach considering multiple data sources i.e. neurophysi-ology, neuropsychology and other structural/functional imagingmodalities.

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p204EX VIVO HIGH-RESOLUTION MR (7T) MICROSCOPYOF THE HUMAN HIPPOCAMPUSR. Coras*, R. Garbelli�, G. Milesi�, C. Frassoni�, I. Zucca�,A. Mastropietro�, A. M�hlebner*, A. Hess�, E. Aronica§,I. Bl�mcke*, and R. Spreafico�

*University Hospital Erlangen, Erlangen, Germany; �I.R.C.C.S.Foundation Neurological Institute, Milan, Italy; �University ofErlangen-Nuremberg, Erlangen, Germany; and §AcademicMedical Centre, Amsterdam, The Netherlands

Purpose: The human hippocampus is morphologically affected in manyneurological disorders such as Alzheimer's disease or mesial temporallobe epilepsy (MTLE). Its internal structure remains, however, difficultto recognize at 1.5T- or 3T-MR imaging. Herein, we aimed to anatomi-cally delineate all subregions and layers of the human hippocampus com-bining high-field 7T-MRI and microscopy from same tissues specimens.

Method: Different imaging protocols were applied on a 7T experimen-tal scanner to examine eight post-mortem human hippocampus speci-mens. Anatomical layers along the anterior-posterior axis of thehippocampus were characterized on T2-weighted coronal sections. His-tological analysis of same specimens was performed to co-register andvalidate 7T-MRI. Three-dimensional T2-weighted imaging and coronalplanes with different angulations were acquired to anticipate the archedshape of the hippocampal head. Fractional anisotropy and color fiber ori-entation maps were used to visualize intrahippocampal projections andfiber tracts.

Result: MR-Intensity differences between anatomical boundaries wereconfirmed by exact confrontation with histology and could be assigned toten clearly recognizable layers. These findings were best visible at thehippocampal mid-body-level. We were able to distinguish all these hip-pocampal subregions also in the hippocampal head with three-dimen-sional T2-weighted imaging and angulated coronal planes. Fractionalanisotropy and color fiber orientation maps visualized intrahippocampalprojections and fiber tracts connecting the hippocampus with the mesialtemporal lobe.

Conclusion: High resolution MR-microscopy identified anatomicalsubcompartments and sublayers as well as distinct fiber tracts along theentire anterior-posterior hippocampal axis, and will be a promising toolfor the investigation of subtle pathology in neurological or neurodegener-ative disorders.

p205INTRACRANIAL EEG-FMRI: MAPPING BRAIN NET-WORKS RELATED WITH ALPHA AND BETA IN SEN-SORIMOTOR CORTEXS. Perani, S. Vulliemoz, R. Rodionov, L. Lemieux, andD. W. CarmichaelUCL Institute Of Neurology, London, UK

Purpose: Alpha (a) and beta (b) are EEG features in the frontal cortex.However, whether alpha and beta originate in spatially independentregions across the sensorimotor cortex and their relationship to differentbrain networks remain unclear. In this study we used simultaneous intra-cranial-EEG-fMRI to study local a and b oscillations and map their hae-modynamic correlates.

Method: One patient with intracranial-EEG (1x57 grid) over the leftsensorimotor cortex underwent T1, two sessions of resting-state and onefinger-tapping fMRI during simultaneous acquisition of intracranial-EEG data. After artifact corrections, electrophysiological signal wastime-frequency transformed and averaged into frequency bands. For eachfrequency band, the power was spatially averaged by taking the first prin-cipal component and convolving with a canonical haemodynamicresponse. Statistical parametric maps of the fMRI changes were obtained

using F-contrasts across the alpha and beta band effects (taken separatelyand together).

Result: a bands were from sensory cortex, b bands were predominantlyrecorded from primary motor cortex. During finger tapping a and b activ-ity correlated significantly respectively with BOLD changes in the rightmotor cortex and bilateral sensory cortices. During rest, activity corre-lated with BOLD changes in the precuneus (a, b), cingulate (a), middleand superior-frontal gyri (a, b), angular (a, b), supramarginal (a, b), lin-gual (b) and inferior-temporal gyri (a) and lateral-occipital (a) cortex.

Conclusion: Intracranial-EEG-fMRI allowed the investigation of a andb generators and the role played in marking brain networks. Indeed, aand b correlated with BOLD changes which mapped the ‘default mode’,fronto-parietal, occipital-visual and occipital-parietal networks and thevisual system.


p206DEFINITION OF A STEREOTACTIC 3D MODEL OFTHE HUMAN INSULA FOR NEUROSURGICALAPPROACH (EPILEPSY AND STEREOTAXIC SUR-GERY)A. Afif*, G. Becq�, and P. Mertens**Neurological Hospital, Hospices Civils de Lyon, Lyon, France;and �Grenoble, France

Purpose: Design a method for 3D reconstruction of the insula, includingits gyri and sulci, in AC-PC reference usable individually for imaging orfor epilepsy and stereotactic surgery.

Method: Morphometric study using 100 MRI of normal insular region.56 male/44 female, 50 left/50 right hemispheres. Stage 1: Reconstructionin AC-PC reference of the insula from 3D-T1-MRI slices 1 mm thick.Stage 2: Digitalization and superposition of data in 3D using PhotoStudiosoftware (Photo Editing Software) system with PC as the center of coor-dinates. Stage 3 : MATLAB software (Mathworks Inc.) was used to trans-form in color values each pixel to obtain a color scale corresponding tothe probability of insula sulci localization between 0% and 100%.

Result: Demonstration of very significant correlations between thecoordinates of the main insular structures (angles, sulci ..) and the lengthof AC-PC. This close correlation allows to describe a method for 3Dreconstruction of the insula on MRI slices that requires only the positionsof Ac and PC and then the inter-commissural (AC-PC) length. This pro-cedure defines an area containing insula with 100% probability.

Conclusion: 3D reconstruction of insula will be potentially useful for:1 To improve localization of cortical areas, allowing to differentiate

insular cortex from opercular cortex during stereoelectroencephalograph-ic exploration of patients with epilepsy (SEEG) or in morphological andfunctional imaging.

2 For microsurgical approach of Insula using Neuronavigation tech-niques.

3 Identification of Insula during stereotactic surgery (SEEG, biopsy).

p207MYOCLONUS CORTICAL GENERATORS IN UNVER-RICHT-LUNDBORG DISEASE: AN ELECTRIC SOURCEIMAGING STUDYA. Del Felice*, C. Arcaro*, L. Canafoglia�, S. Franceschetti�,A. Fiaschi*, and P. Manganotti*

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*Universit degli Studi di Verona, Verona, Italy; and �IRCCSFoundation Besta Neurological Institute, Milan, Italy

Purpose: To localize the cortical generator of myoclonic jerks in pro-gressive myoclonic epilepsy (Unverricht-Lundborg disease) applying theElectrical Source Immaging method (ESI).

Method: 3 patients (2 female, 1 male, age: 17–48 yrs) affected by Un-verricht-Lundborg disease underwent a 256—channels EEG with con-comitant polygraphic recording. Provocative manouvres were conductedduring the exam to elicit myoclonic jerks. EEG (electroencephalo-graphic) and EMG (electromyographic) traces were analyzed off line.For the other 2 patients, a back-averaging of the myoclonic EMG activityand corresponding EEG abnormalities was performed. Analysis was con-ducted off line. A mean of 15 jerk-locked EEG potentials for eachpatients were averaged, and projected through a LORETA algorithm onan MNI (Montreal Neurological Institute) brain template in order to iden-tify the cortical generator.

Result: Jerk-locked EEG potentials were recognizable over the centro-frontal derivations, with a slight lateralization in each single case. ESIelaboration localizes the cortical generator over the anterior premotorfrontal cortex (pt 1: Brodman area 6, pt 2: Brodman area 10; pt 3: Brod-man area 11), with a lateralization concordant with the EEG potentials (2right hemisphere, 1 left).

Conclusion: ESI is a technique that permits cortical source localizationof EEG potentials. Its application to this rare form of epilepsy depicts theimportant role of the pre-motor and frontal cortex in the myoclonic jerk'sgeneration. To our knowledge, this is the first report describing the corti-cal source generation from the anterior/premotor cortex. Since only thejerk-locked potential was examined, we can not infer on the involved net-works.

p208A NOVEL METHOD FOR THE CLASSIFICATION OFINTERICTAL EEG ABNORMALITIES IN PARTIAL EPI-LEPSY: AN EEG-FMRI VALIDATION STUDYA. E. Vaudano*, C. Pedreira�, R. Thornton�, U. Chaudhary�,S. Vulliemoz§, H. Laufs–, R. Rodionov�, R. Quian Quiroga�, andL. Lemieux�

*University of Modena e Reggio Emilia, Modena, Italy; �TheUniversity of Leicester, Leicester, UK; �University College ofLondon Institute of Neurology, London, UK; §UniversityHospital of Geneva, Geneva, Switzerland; and –JohannWolfgang Goethe University, Frankfurt, Germany

Purpose: Scalp recordings and classification of interictal EEG dis-charges (IED) in patients with epilepsy potentially provide valuableinformation about the epileptogenic network, particularly by defining theboundaries of the ‘‘irritative zone’’, and hence being helpful during pre-surgical evaluation. Detection and classification of the signals rely inexpert observers which can be a time-consuming procedure and presentsinter-observer variability. Here, we propose a novel approach: the auto-matic classification of events using the spike sorting algorithm Wave_-clus. This method aims to reduce processing time and provide moreobjective classification of events.

Method: We applied the automatic sorting to the signals collected fromEEG/fMRI presurgical evaluation recordings in 8 patients (6 males, meanage: 27) affected by refractory partial epilepsy. For each patient, twofMRI analyses were performed: one based on the visual classificationand the automatic IED sorting. All fMRI data were pre-processed andanalysed using SPM8.

Result: In all cases, BOLD mapping of IED classified with wave_clusreproduced the hemodynamic maps related to the visually labeling. In 7cases, Wave_clus classification also provided additional fMRI clusters.

The level of concordance between fMRI maps derived from the Wave_-clus classification and the electro-clinical data was higher for 5 patientscompared to the manual classification, and unchanged in the remaining 3.

Conclusion: We propose that the use of spike sorting algorithms to clas-sify IED is an efficient tool for mapping the fMRI changes linked to IED,potentially saving time and effort, and increasing the technique's clinicalvalue.

p209FLUMAZENIL IS A WEAK SUBSTRATE FOR P-GLYCO-PROTEIN IN HUMANS. A PET STUDY IN PHARMACO-RESISTANT PATIENTS WITH UNILATERAL MTSF. E. Froklage*, A. Postnov*, N. H. Hendrikse*,J. C. Reijneveld*, J. J. Heimans*, R. Boellaard*,A. A. Lammertsma*, and R. A. Voskuyl�

*VU Medical Center, Amsterdam, The Netherlands; and �

Leiden/Amsterdam Center for Drug Research, Leiden, TheNetherlands

Purpose: Pharmacoresistance in epilepsy may be caused by limited drugtransport across the blood-brain barrier (BBB) due to increased activityof efflux transporters, such as P-glycoprotein (P-gp). Recent data suggestthat flumazenil might be a P-gp substrate. If this is correct, increase in P-gp function in epilepsy could confound the interpretation of resultsobtained in PET studies with [11C]flumazenil.

Method: For this study 10 pharmacoresistant patients with unilateralmesial temporal sclerosis were selected. They were studied twice with[11C]flumazenil, i.e. in the morning and in the afternoon. Before the after-noon scan 2 mg/kg tariquidar (a P-gp blocker) was administered i.v. In 5patients both [11C]flumazenil scans were preceded by [15O] water scansto measure possible changes in blood flow.

Result: Blood flow was not affected. Analysing the [11C]flumazenildata with the one-tissue plasma input model demonstrated a slightincrease in distribution volume (VT) from 5.3 € 0.8 to 5.7 € 0.3 (p = 0.1,paired t-test). The simplified reference tissue model with the Pons as ref-erence was used to determine BPND. The morning scans demonstrated aBPND of 4.7 € 1.0 which slightly decreased to 4.2 € 0.5 in the afternoonscan (p = 0.2). Transfer of the tracer across the BBB was estimated bytaking the ratio of VT and 1 + BPND which equals to K1/k2. The K1/ k2

value of 0.92 € 0.14 increased significantly to 1.1 € 0.1 (p = 0.003, pairedt-test) after the second scan.

Conclusion: The significant increase in K1/k2 suggests that flumazenilmay be a P-gp substrate. Whether the small decrease in uptake in pharma-coresistant patients is clinically relevant remains to be determined.

p210ICTAL PET FINDINGS IN PATIENTS WITH REFRAC-TORY FOCAL EPILEPSYG. Kuester*, S. Marca*, D. Ladron De Guevara*, L. Rios*,F. Solari*, R. Gejman�, M. Galvez*, and M. Campos**Clinica Las Condes, Santiago, Chile; and �P.U. Catolica DeChile, Santiago, Chile

Purpose: To present four patients whose PET showed well-localized hy-permetabolic foci corresponding to the seizure onset area.

Method: Four patients with refractory focal epilepsy studied withVideo-EEG monitoring, brain MRI, PET, intraoperative EcoG.

Result: Case-1: R. frontal FCD, R. frontal seizures. PET: R. anteriorfrontal hypermetabolism. Surgery: frontal topectomy. Histopathology:

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type II-B FCD. Seizure free, 24 mo. follow-up. Case-2: R. hippocampalsclerosis, R. mesial temporal seizures. PET: R. hippocampal hypermetab-olism, mild/diffuse R. temporal hypometabolism. Surgery: R. anterior-mesial temporal resection. Histopathology: type II-B FCD of the end foli-um of the hippocampus, WM gliosis. Seizure free, 21 mo. follow-up.Case-3: MRI-1: R. occipital FCD, MRI-2: R. anterior temporal FCD.Video-EEG-1: R. temporo-occipital seizures, Video-EEG-2: R. temporalseizures. PET-1: R. occipital hypermetabolism, PET-2: R. anterior tem-poral hypermetabolism. Surgery 1: R. occipital lobectomy, Surgery 2: R.temporal lobectomy-frontal topectomy. Histopathology: II-A FCD/poly-microgyria. Seizure free, 18 mo. follow-up. Case-4: R. posterior-mesialtemporal cavernoma, R. hippocampal sclerosis. EEG: intermittent R.frontotemporal slowing without ictal findings. PET: R. amigdala hyper-metabolism. ECoG: continuous ictal/interictal discharges over R. hippo-campus/amigdala. Surgery: cavernoma/anterior hippocampus/amigdalaresection. Seizure free, 3 mo. follow-up.

Conclusion: Interictal PET showing hypometabolic foci is a valuabletool in presurgical evaluation of focal epilepsy. However, correlations ofwell-localized hypermetabolic abnormalities/histopathology/postsurgi-cal outcomes has not been delineated. In our patients hypermetabolic focihad excellent correlation with seizure onset/histopathology. Hypermeta-bolic changes could be a signal of very frequent electrographic/subclini-cal seizures. Although this is a small series and follow up is not longenough, we suggest that ictal PET can provide good information aboutseizure onset area.

p211MOTOR CIRCUIT TRACTOGRAPHY PREDICTSMOTOR PERFORMANCE IN CHILDREN WITH RO-LANDIC EPILEPSYL. M. Brindley*, F. M. Gibbon�, A. Kirby�, L. Peters�, J. TeWater Naude�, M. Thomas�, N. Williams�, K. D. Singh*,D. K. Jones*, and K. Hamandi§

*Cardiff University, Cardiff, UK; �Cardiff and Vale UniversityHealth Board, Cardiff, UK; �University of Wales, Newport,Newport, UK; and §University Hospital of Wales, Cardiff, UK

Purpose: Rolandic epilepsy, characterised by focal motor seizures, hasbeen associated with motor coordination disorders. This was investigatedusing the Movement Assessment Battery for Children (MABC-2) andconstrained spherical harmonic deconvolution (CSD) tractography inchildren with rolandic epilepsy.

Method: Eight right-handed children with rolandic epilepsy (3 females)aged 9–12 years completed the MABC-2 and underwent diffusion-weighted magnetic resonance MR imaging.

Whole-brain CSD tractography was computed and the AAL-labellingatlas warped back into native DWI space for each individual. Partial vol-ume correction for CSF contamination was applied. Mean fractionalanisotropy (FA) was assessed for left hemispheric tracts between the fol-lowing ROIs: SMA; M1; thalamus; cerebellum; basal ganglia.

These data were entered as predictor variables in separate stepwiselinear regression procedures for each of the age-normalised MABC-2sub-component and overall percentile scores.

Result: MABC-2 scores (mean:18.1, SD:16.9) were variable but signifi-cantly below the population mean (t (7)=-5.322, p=.001). Three childrenscored below the 5th percentile.

Higher mean FA of tracts connecting SMA and thalamus predictedbetter scores upon overall MABC-2 (r=.892, p=.003), manual dexterity(r=.917, p=.001) and balance (r=.968, p<.001). Lower mean FA of tractsconnecting basal ganglia with SMA predicted better ball skills (r=-.758,p=.029).

Conclusion: Mean FA within specific motor tracts is predictive of motorabilities in a population of children with rolandic epilepsy and variablemotor function.

Differences in FA of thalamo-cortical and cortico-striatal motor tractsmay reflect differences in excitatory and/or modulatory connections,with impacts upon control of voluntary movements and motor learning.

Acknowledgement: This research was funded by the Waterloo Founda-tion.

p212TEMPORAL POLE ASYMMETRY IN TEMPORALLOBE EPILEPSY PATIENTSL. Martinkovic*, D. Horinek�, O. Bradac�, T. Belsan�, andP. Marusic�

*Charles University in Prague, Prague 5, Czech Republic;�Marburg, Germany; and �Prague 6, Czech Republic

Purpose: The aim was to assess temporal pole volume (TPV) in a groupof patients with mesial temporal lobe epilepsy (MTLE) and in healthycontrols. Our hypothesis was that TPV asymmetry can distinguish MTLEpatients from controls.

Method: Fifteen patients diagnosed with refractory unilateral MTLEassociated with hippocampal sclerosis (6 right-sided, 9 left-sided) and 30healthy controls were included. Based on high-resolution MRI left (L)and right (R) temporal pole volumetry was manually performed. The firstslice where temporal stem was clearly identified was considered as pos-terior border. TPV asymmetry was defined by asymmetry index (AI) cal-culated as 2*(L-R)*100/(L+R). TPVs (ipsilateral vs. contralateral side tothe epileptogenic zone) were also compared in MTLE patients.

Result: There was high variability in TPV asymmetry in control group(AI 2.4; SD 10.0) and in patients (AI 2.2; SD 17.1). In four MTLEpatients only AI was significantly (>2 SD) higher than values observed incontrols. In patients TPV ipsilateral to the epileptogenic zone was smaller(17.4 € 3.7 cm3) than contralateral volume (19.2 € 3.4 cm3; p < 0.005).

Conclusion: There is a high variability in TPV asymmetry both inMTLE patients and in healthy controls. Asymmetry index itself does notallow to differentiate most of MTLE patients from controls. Temporalpole ipsilateral to the side of epilepsy is likely to be smaller in refractoryunilateral MTLE patients.

p213COMPARATIVE VALUE OF SISCOM, FDG-PET ANDINTRACRANIAL EEG IN PATIENTS WITH NON-LE-SIONAL EXTRATEMPORAL EPILEPSYM. Kudr*, P. Krsek*, A. Jahodova*, J. Rybar*, J. Trnka�,M. Jaruskova�, K. Michalova*, J. Sanda*, M. Kyncl*,J. Zamecnik*, M. Tichy§, and V. Komarek**University Hospital Motol, Charles University, 2nd MedicalSchool, Prague, Czech Republic; �Charles University, 1stMedical School, Prague, Czech Republic; �Na HomolceHospital, Prague, Czech Republic; and §University HospitalMotol, Prague, Czech Republic

Purpose: To assess a practical value of SISCOM, FDG-PET and intra-cranial EEG in the localization of the epileptogenic zone in patients withintractable focal epilepsy and normal MRI finding.

Method: A group of 14 patients operated on because of intractable epi-lepsy due to MRI-negative focal cortical dysplasia (FCD) was retrospec-tively studied. We coregistrated preoperative SISCOM and PET imageswith postoperative MRI and visually determined whether cerebral cortexunderlying the SISCOM focus, PET hypometabolism area and cerebralcortex exhibiting prominent abnormalities on EEG was completelyresected, incompletely resected or non-resected. These results and histo-pathological findings were compared with postoperative seizure out-comes.

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Result: 13 from 14 patients had a localizing SISCOM. PET findingswere normal in three subjects; two of them had favorable postsurgicaloutcomes. All patients with completely resected SISCOM focus (n = 2),PET hypometabolic area (n = 2) or cortical region exhibiting significantintracranial EEG abnormality (n = 7) had favorable outcomes. By con-trast favorable outcome was achieved only in some patients with incom-pletely (five of nine) or non-resected SISCOM focus (one of two),incompletely (four of seven) or non-resected PET hypometabolism area(one of two) and incompletely resected intracranial EEG abnormality(two of seven). No correlation between histopathological types of FCDand seizure outcome was found.

Conclusion: Complete resection of the dysplastic cortex localized by acombination of SISCOM, FDG-PET and intracranial EEG is a reliablepredictor of favorable postoperative seizure outcome in patients withintractable non-lesional extratemporal epilepsy.

Supported by IGA NT/11443—5, Kontakt Program ME09042,CZ.2.16/3.1.00/24022 and GAUK 17010.

p214RELIABILITY OF MEMORY FMRI IN TEMPORALLOBE EPILEPSY PATIENTSK. Towgood*, A. Caceres*, S. Costafreda*, G. J. Barker*,W. Crum*, R. D. Elwes�, M. Mehta*, and M. P. Richardson**King's College London, London, UK; and �King's CollegeHospital, London, UK

Purpose: Functional MRI (fMRI) of memory functions is emerging as amodality of investigation in presurgical evaluation of mesial temporallobe epilepsy (mTLE). The reliability and reproducibility of the methodis not known.

Method: Eighteen subjects with mTLE were scanned over three ses-sions at intervals of 2 weeks. Each session comprised; (1) HometownWalk, blocked design; (2) Scenes protocol, block design (Scene View-ing) and event-related design (Scene Encoding); (3) Words and picturesprotocol, material-specific blocked designs (Picture Viewing, WordViewing) and event-related designs (Picture Encoding, Word Encoding).Therefore 7 activation maps were produced per subject per session, 378datasets in total. We examined between-sessions reliability of activationusing intraclass correlation coefficients; the spatial overlap of the ana-tomical location of activation peaks between sessions; and the ability ofeach activation map to predict the side of seizure onset.

Result: Reliability between sessions 1 and 2 was similar to reliabilitybetween sessions 2 and 3. Hometown Walk and Scene Viewing weremost reliable (ICCs 70.73 and 64.88 respectively), and Word Encodingleast (ICC 30.79). The spatial overlap of the anatomical location of acti-vation peaks between sessions showed similar differences between proto-cols.

Conclusion: We recommend that future evaluations of memory fMRI inmTLE should use two fMRI tasks: Word Encoding, and either Home-town Walk or Scene Viewing.

p215GRANGER CAUSALITY ANALYSIS OF RESTING-STATE NETWORKS IN POST-TRAUMATIC EPILEPSYPATIENTSH. A. Ferreira*, A. C. Borralho�, P. M. GonÅalves-Pereira�,R. ManaÅas§, and A. Andrade**Faculdade de CiÞncias da Universidade de Lisboa, Lisboa,Portugal; �Instituto Polit�cnico de Lisboa, Lisboa, Portugal;�Hospital dos Lus�adas, Lisboa, Portugal; and §Hospital dosCapuchos, Lisboa, Portugal

Purpose: Granger causality analysis(GCA) was used to investigate howthe temporal epileptic network(TEN) relates causally with other resting-state networks(RSN) and what changes are observed in post-traumaticepilepsy(PTE) patients.

Method: This study encompassed 24 healthy subjects and 3 PTEpatients. Resting-state fMRI data was acquired in a 1.5T scanner using aBOLD sequence with TR=2 s. Data was pre-processed in DPARSF1.0software, using a 0.01–0.073 Hz filter. REST1.6 software was used forGCA based on signed path coefficients(SPC) and order 1. RSN were usedas ROI seeds: TEN, comprised of the amygdala, hippocampus and para-hipocampus; default-mode network(DMN); sensorimotor net-work(SMN); visual network(VN); attention network(AN); anteriorcingulate(AC), and insula. ROI-wise analysis was done between pairs ofnetworks and voxel-wise analysis was done using TEN as seed. Causalinfluences between networks were studied in healthy subjects andchanges in patients were evaluated using two-sample t-test(p < 0.05).

Result: TEN was shown to influence all RSN (positive SPC), with theexception of the VN(probably because a visual stimulus is first processedat the VN before being made available to other networks). The positivecausal effect is stronger with the AC, AN and insula, which could trans-late a stronger influence on cognitive and emotional processes. Allpatients showed causal changes involving TEN, DMN and SMN, inagreement with known memory and motor impairments. Additionalchanges were observed in the AN and insula for individual patients.

Conclusion: Although preliminary, this study shows GCA as a potentialtool to evaluate causal functioning of RSN in PTE patients. In particular,changes were consistently observed in TEN, DMN and SMN.

Paediatric Epileptology 1Monday, 01 October 2012

p216SEIZURE BURDEN IN NEONATAL HYPOXIC ISCHE-MIC ENCEPHALOPATHY: THE MODIFYING ROLE OFPHENOBARBITONE DURING THERAPEUTIC HYPO-THERMIAN. E. Lynch*, N. J. Stevenson*, B. P. Murphy*, J. M. Rennie�,and G. Boylan**University College Cork, Cork, Ireland; and �UniversityCollege Hospital, London, UK

Purpose: Our aims were to investigate the distribution of seizure burdenover time in infants with Hypoxic Ischemic Encephalopathy (HIE)receiving whole-body hypothermia (TH) and to investigate the effect ofphenobarbitone (PB).

Method: Full- term newborns with moderate and severe HIE, seizures,and continuous video EEG monitoring who received TH were includedin this study. All EEG seizures were annotated and the seizure period,defined as the period between the first and last recorded electrographicseizure, the seizure burden per hour and the time-point of maximum sei-zure burden was identified. Subgroup analysis of seizure burden distribu-tion in moderate and severe HIE was performed. Pearson's correlationcoefficient was used to investigate correlation between maximum seizureburden and time of PB administration. A significant correlation betweenmaximum seizure burden and PB administration indicates a reduction ofseizure burden after PB.

Result: 24 infants were included, 13 with moderate HIE, 11 with severeHIE. Infants with severe HIE had a short period of high seizure burdenfollowed by a long period of low seizure burden (median total period47.9 hrs). There was no correlation between maximum seizure burdenand PB administration. In moderate HIE, there was a shorter total seizure

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period (median 11. 3 hrs) and strong correlation between PB administra-tion and maximum seizure period (correlation coefficient= 0.9919; p-value<0.001).

Conclusion: In this study we demonstrate a significant correlationbetween maximum seizure burden and PB administration in moderateHIE indicating a reduction of seizure burden following PB. This is notseen in severe HIE.

p217IN DEPTH’ PERFORMANCE ANALYSIS OF A NOVELAUTOMATED SEIZURE DETECTION ALGORITHMFOR NEONATAL EEGS. Mathieson*, R. M. Pressler�, J. M. Rennie*, N. J. Stevenson�,L. Marnane�, and G. Boylan�

*University College Hospital, London, UK; �Great OrmondStreet Hospital for Children, London, UK; and �UniversityCollege Cork, Cork, Ireland

Purpose: Neonatal seizures can be reliably detected with EEG but avail-ability of trained neurophysiologists out of hours is often limited. Tofacilitate seizure detection for clinical purpose, a novel seizure detectionalgorithm (SDA) has been developed (Neonatal Research Group, UCC,Ireland). The aim of this study was to introduce a novel neurophysiology-based performance analysis of the SDA in which multiple features of sei-zures were quantified so as to determine the differences between detectedand non-detected groups (by the SDA) and sources of artifact causingfalse detections.

Method: Seizures from 20 neonates were visually annotated and char-acterised using 10 criteria, including length, frequency change, rhyth-micity, peak amplitude, waveform morphology, number of EEGchannels involved and background pattern. Seizure annotations fromthe SDA were compared to those from visual analysis to derivedetected and non-detected groups and seizure characteristics were sta-tistically compared. Causes of false detections were determined. Statis-tical tests included the Mann Whitney U test, Chi Squared and Fisher'sExact Test.

Result: There were significant differences between the groups in 9/10criteria. Detected seizures were longer, more rhythmic, had higher peakamplitude, involved more EEG channels, and had greater frequency andmorphology change over the seizure. Certain seizure morphologies werebetter detected than others. Background EEG had no influence on detec-tion. Primary causes of false detections included respiration, sweat orpulse artefact or a highly rhythmic background.

Conclusion: This analysis has identified key areas for SDA modifica-tion, which should lead to improved performance.

p218DELTA FREQUENCY SEIZURES ARE COMMON INSICK NEWBORNS AND CAN BE EASILY RECOGNISEDUSING A SIMPLE ADAPTATION TO AMPLITUDEINTEGRATED EEGT. V. StanleyUniversity of Otago Wellington, Wellington, New Zealand

Purpose: Delta frequency seizures were accidentally noted in an infantundergoing routine amplitude integrated EEGs (aEEG) whilst being trea-ted for gram negative meningitis. We elected to discover how commonlyelectrical seizures in the delta range were recognizable in aEEGs per-formed in sick newborns where seizure activity had not previously beenreported to be present, and to delineate in which newborn conditions theywere most commonly seen.

Method: All neurologically sick term newborn aEEG records storedsince 2004 where no seizures had been seen using standard methods werereviewed using a 60 second view which allowed slow seizures (<4 Hz) tobe easily recognized. The final discharge diagnosis in those with andwithout such seizures were examined.

Result: delta frequency seizures were common in neurologically sickinfants without higher frequency seizure activity. They were often ofrelatively low voltage (<25 mcV) but commonly prolonged for over 10minutes.

Conclusion: seizures in the delta frequency are common in sick termneonates although not much described in the EEg literature and notreported in the aEEG literature. At present their prognostic implicationsare unknown.

p219AMPLITUDE-INTEGRATED ELECTROENCEPHALOG-RAPHY AND ELECTROENCEPHALOGRAPHY IN NEO-NATESW. Kim*, and G. Sim�

*Chungbuk National University Hospital, Cheongju, Korea;and �Cheongju Saint Mary Hospital, Cheongju, Korea

Purpose: Amplitude-integrated electroencephalography (aEEG) allowssimplified monitoring of cerebral function and its use for bedside deci-sion-making is increasing. We studied aEEG in a cohort of neonates.

Method: We studied 32 neonates who were admitted to our hospitalfrom January 2009 to February 2010. We retrospectively studied EEG,aEEG and brain sonography of neonates who had clinical seizures,apnoea or desaturations.

Result: Twenty-two (71.9%) of 32 neonates who had clinical seizures,apnoea or desaturations in the neonatal intensive care unit (NICU) had anaEEG. In the aEEG, 15 (62%) showed seizures, 4 (16%) showed suppres-sion, 5 (20%) showed an abnormality. The correlation between EEG andaEEG was significant (p < 0.005). Of the neonates who had aEEG, 11(34.3%) had clinical seizures, 22 (68.7%) had apnoea and 21 (65.6%) haddesaturations. In patients with abnormal aEEG, the following brainsonography abnormalities were demonstrated: increased periventricularechodensities (41%), germinal matrix hemorrhage (41.1%) and brainswelling (8%). Abnormal aEEG was significantly associated with abnor-mal sonography (p < 0.05).

Conclusion: The correlation of EEG and aEEG in NICU has been dem-onstrated in this study. Therefore, aEEG monitoring can help with thedetection of seizures in neonates.

p220THE APPLICATION OF MULTICHANNEL AMPLITI-TUDE-INTEGRATED EEG WITH SIMULTANEOUSLYVIDEO EEG IN NEONATAL SEIZUREX. Zhu*, and Y. Wang�

*Children's Hospital of Fudan University, Shanghai, China;and �Shanghai, China

Purpose: To assess the accuracy of amplititude-integrated EEG (aEEG)used to diagnose neonatal seizure, using video EEG (VEEG) as a goldstandard, with regard to both the background pattern and the recognitionof epileptiform discharges in neonates who have suspected clinical sei-zures.

Method: 66 neonates with suspected clinical seizure were investigatedand bedside VEEG was recorded for ‡3 hours. VEEG signals were trans-formed into aEEG signals. Background pattern of aEEG and VEEG were

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analyzed independently and classified. 39 infants with VEEG epilepti-form activities (‡10 s) were investigated, and calculated for single- andmultichannel aEEG identified with ‡1 epileptiform activity.

Result: 62 traces were suitable for analysis. A normal background aEEGcorresponded with a normal or mild abnormal EEG in 100% of the cases.The PPV for a severely abnormal aEEG (BS, CLV, FT) to correspondwith a severely abnormal EEG was 83% (NPV, 96%; sensitivity, 83%;specificity, 96%). On VEEG, 326 epileptiform activities with a meanduration of 78 s were identified. The sensitivity of aEEG for the detectionof epileptiform activities was 40% for single-channel aEEG and 51% formultichannel aEEG. Multichannel aEEG identified 95% patients with ‡1epileptiform activities, whereas single-channel aEEG (C4–C3) identified82%.

Conclusion: CFM is a reliable tool for monitoring both background pat-terns (especially normal and severely abnormal) and epileptiform activi-ties. Epileptiform detection rate is slightly better with multichannelaEEG compared with single-channel aEEG. We recommend using multi-channel aEEG as a monitoring device and performing intermittent stan-dard VEEG whenever there is any doubt about the classification of theaEEG.

p221DIAGNOSIS OF NEONATAL SEIZURES: EFFECTIVE-NESS OF CURRENT CLASSIFICATION SYSTEMSL. Menzies*, H. Cross�, and R. M. Pressler**UCL-Institute of Child Health, London, UK; and �UniversityCollege London, London, UK

Purpose: It is agreed that classification of seizures is important toorganizing information for purposes of drug development, clinicaland basic research, and of course, clinical practice. In contrast to anagreed and repeatedly updated system for older children and adults(ILAE), at least 3 systems are in use for neonatal seizures with littleagreement of their value and practicability. We aimed to assess howwell these systems identify and classify neonatal seizures in clinicalpractice.

Method: We identified neonates with seizures form the EEG database attertiary referral centre (GOSH, UK). Electroclinical, clinical only (noEEG correlate) and electrographic (subclinical) events were classifiedaccording to semiology in three classification systems used in clinicalpractice: Volpe, Mizrahi and ILAE 2010 proposed system.

Result: We identified 47 infants (85% term babies) with a total of 285events (38% electroclinical, 26% clinical, 36% electrographic) and aduration of 857 sec/hour (26% electroclinical, 6% clinical, 68% electro-graphic). In the Volpe classification 45% of events were classifiable,18% partially classifiable and 36% unclassifiable, in the Mizrahi classifi-cation 77% of events were classifiable, 22% partially classifiable and 1%unclassifiable and in the ILAE classification 41% of events were classifi-able, 19% partially classifiable and 40% unclassifiable. Unclassifiableevents were mostly electrographic events.

Conclusion: Overall the value of classifications was poor: 2 of the 3classification systems could classify less than half of seizures. This isthought to be due to the high proportion of electrographic seizures anddue to the differing seizure semiology in new-born babies.

p222CLINICAL AND ELECTROGRAPHIC PATTERN COR-RELATES IN NEONATAL SEIZURESM. M. Awadh*, V. Jain�, and M. E. O’Regan�

*Ain Shams University Hospitals, Cairo, Egypt; and �RoyalHospital for Sick Children, Glasgow, UK

Purpose: Clinical recognition of neonatal seizures is challenging. Elec-trographical (EEG) ictal activity have various clinical presentations andelectro-clinical Decoupling (ECD) is common after AED.

Method: Analysis of video EEGs (30 minutes) recorded before 44weeks corrected age neonates at risk of or already with suspect seizuredisorders.

Result: Of 164 consecutive recordings (2007–2010), 37 neonates(22.5%) had either EEG or clinical events; 7 preterm and 20 (54%) pre-loaded with AED, 31 had manifest suspect seizures before recording & 6encephalopathic. 165 EEG seizures were captured in 23 infants, 50(30.3%) had clinical correlates; 170 suspect clinical events were cap-tured, 120 (70.5%) lacked EEG ictal discharge; 14 (37.8%) babies hadonly non-ictal events. No relation was relevant between EEG seizure fre-quency, onset zone, regional or contralateral propagation and the mani-fest clinical phenomena. 3 EEG seizures less than 10 seconds wereassociated with subtle events. Mouth twitching was apparent in two caseswith ipsilateral Rolandic ictal discharges. EEG seizures were adverselycorrelated to clinical development (p = 0.045), not the mortality (p =0.07). Their number was highly predictable of postneonatal seizures (p =0.003). This was true for number of electro-clinical decoupling (p =0.025), and captured clinical events (p = 0.001).

Conclusion: Most of recognizable suspect clinical phenomena are notgenuine seizures. Avoidance of prompt treatment with non-indicatedAED on clinical suspicion might prevent unnecessary deleterious devel-opmental iatrogenic effects on growing brain. Despite the poor prognos-tic implications, probably denoting underlying pathology rather thandirect seizure effect, lack of clinical consistency of neonatal seizuresmight be explained by the immature cortical topographic functional dif-ferentiation.

Semiology, Aetiology and Classification 1Monday, 01 October 2012

p223SCREENING FOR SYMPTOMS OF ANXIETY ANDDEPRESSION IN PATIENTS WITH PSYCHOGENICNONEPILEPTIC SEIZURESA. Z. Ilic*, and D. J. Milivojevic�

*Health Center Studenica, Kraljevo, Serbia; and �MedicalCentre Petrovac, Petrovac, Serbia

Purpose: Psychogenic nonepileptic seizures (PNES) are somatic mani-festations of psychologic distress. This study compared anxiety anddepression in patients presenting with psychogenic non-epileptic seizures(PNES) with those suffering from epilepsy.

Method: This clinically descriptive, prospective study involved consec-utive patients who fulfilled the clinical and video-EEG criteria for PNESand epilepsy, and who were recruited over an 18—month period. All sub-jects were assessed for symptoms of anxiety and depression with Hamil-ton Anxiety Rating Scale and Hamilton Depression Rating Scale. Qualityof life was assessed with Sickness Impact Profil. Clinical follow-up wasconducted 8–12 months after the first evaluation.

Result: A total of 22 patients were recruited: 11 presented with PNESwithout epilepsy; and 11 had epilepsy. Both patient groups had similarage, sex and education level. Anixiety and depression values were in91% and in 54,5% of the ptients with PNES; and in 45,4% and in 18,8%in epilepsy group. Depression and anxiety were increased in PNES groupcompared to the group with epilepsy and correlated significantly withperceived restrictions due to disease, tolerability and efficacy of drugtherapy, financical situation and education, self-efficacy, social supportand with the global quality of life. Although seizure control is important

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in both disorders, seizure remission is not a comprehensive measure ofgood outcome in PNESs.

Conclusion: The prevalence of anxiety and depression in PNES group isconsiderably higher than in the epilepsy group. Seizure control shouldnot be the only focus of treatment in PNES patients and should be com-plemented by appropriate psychiatric and psychological care.

p224PSYCHOGENIC NONEPILETIC SEIZURES IN VIDEO-EEG MONITORING UNIT: SPONTANEOUS SEIZURESAND EFFECTIVITY OF PROVOCATIVE TECHNIQUEI. Mareckova, Z. Vojtech, T. Prochazka, and L. KramskaNa Homolce Hospital, Prague, Czech Republic

Purpose: To evaluate the effectiveness of provocative technique in pat-iens with psychogenic nonepileptic seizures (PNES).

Method: We reviewed medical records of 1378 patients with pharmaco-resistant seizures who underwent long term (5–7 days) video-EEG moni-toring at tertiary care epilepsy center from January 2000 to December2011. All patiens underwent routine evaluation (video-EEG, brain MRIand complete neuropsychological examination). In patiens who had nothad spontaneous seizures we used suggestion and intravenous salineinjection.

Result: We identified 231(17%) patients with various types of PNESwithout background of epilepsy. There were 154 (67%) women and 77(33%) men. 81(36%) patients had their habitual seizure spontaneously,64 (42%) of women compared to 20 (26%) of men. 110 (49%) patientswere induced. In 98 (89%) of them the procedure was diagnostic, 67(44%) women and 31 (40%) men. In 12 (11%) the procedure was nega-tive. In 23 (10%) patients the diagnosis of PNES was based on a clinicalhistory. 12 (5%) of patients signed negative revers.

Conclusion: Our results proved a high effectiveness of suggestive sei-zure provocation. Considering controversies of this technique we areconvinced about its usefulness as only a minority of patiens had theirspontaneous seizures during video-EEG monitoring. Delayed diagnosiscould lead to iatrogenic complications, is costly to patients, the healthcare system and society. It is obvious that correct diagnosis is neccessaryto prevent these consequenses.

p225COGNITIVE AND SOMATIC SYMPTOMS OF ANXIETYDURING DISSOCIATIVE AND EPILEPTIC SEIZURESL. H. Goldstein*, R. S. Delamont�, and J. D. C. Mellers�

*Institute of Psychiatry, King's College London, London, UK;�King's College Hospital NHS Foundation Trust, London; and�South London & Maudsley NHS Foundation Trust, London, UK

Purpose: To extend our previous investigations of the presence of anxi-ety-related seizure symptoms in adults with dissociative (psychogenicnonepileptic) seizures (DS) compared to partial epilepsy patients (ES).

Method: 28 DS and 35 ES patients, without comorbid panic disorder,were recruited from an inpatient videoEEG telemetry unit. Within 36hours of a seizure, patients completed questionnaires indicating the pres-ence or absence (before/during/after that seizure or ever related to a sei-zure) of epilepsy-related symptoms and somatic or cognitive symptomsof anxiety, particularly panic. Measures of anxiety and depression werealso completed.

Result: Unlike our previous study, DS patients had significantly higheranxiety and depression scores than the ES group. Adjusting for anxiety(as well as duration of seizure disorder) reduced between-group differ-

ences in the numbers of somatic symptoms of arousal between the twogroups, particularly occurring during the recent seizure, which otherwisetended to be higher in the DS group. Of particular interest, the DS patientsreported higher levels of cognitive symptoms of panic after, rather thanduring, either their most recent or ever experienced seizures than did theES group; for both time periods anxiety was a significant predictor ofsymptom number.

Conclusion: Anxiety level was a significant predictor of seizure-relatedautonomic and somatic symptoms that appear to differentiate betweenDS and ES patients. Evidence of more extensive negative cognitive inter-pretations following DS seizures, even after adjusting for anxiety levels,suggests that negative seizure-related cognitions are particularly charac-teristic of DS patients, may serve to maintain the disorder and should beaddressed in cognitive behavioural therapy.

p226THE ROLE OF ELECTROENCEPHALOGRAPHY INDIAGNOSTICS OF CENTRAL NERVOUS SYSTEM(CNS) STRUCTURAL LESIONS IN CHILDREN WITHMINOR NEUROLOGICAL SYMPTOMSO. Kozhevnikova, O. Klochkova, O. Logacheva, L. Namazova-Baranova, and A. AnikinScientific Centre of Children Health, Moscow, RussianFederation

Purpose: to assess the possibilities of electroencephalography (EEG) indetecting the structural lesions of CNS, to evaluate its correlation withmagnetic-resonance imaging (MRI) findings in children with minor neu-rological symptoms.

Method: 182 children (7 months – 18 years old) with minor neurologicalsymptoms underwent video-EEG on digital electroencephalographymachines «Bravo NicOne» (Nicolet, USA). All children under 3 yearsand some after 3 years underwent EEG during the day sleep. Patients’main complaints included headaches (27%), single or first episode of sei-zures (25%), hyperexcitement (14%), fatigability (13%), syncopes(10%). All children had pathology according to perinatal anamnesis.Brain MRI's were done on ‘‘Signa Twin speed Excite 1,5 T1 TomographyMachine’’ (GE, USA).

Result: 163 (89,6%) children with minor neurological symptoms andminimal changes on EEG had alterations of structure or/and brain vesselsaccording to MRI. 140 patients (76,9%) had pathological changes onEEG accompanied by structural changes on MRI, herewith 36 children(26%) had angiopathy. Among structural disorders dominated local sub-atrophy and ventriculomegaly 23 (12,6%) patients with EEG disordershad only vessels deviations (S-shape deformation of internal carotidartery (ICA), flexura of ICA or vertebral artery (VA), hypoplasia of VAand combination of hypoplasia and deformation of ICA and VA, narrowICA).

Conclusion: We recommend to analyse the EEG in children under 3years only during the sleep and send children with EEG changes to MRIinvestigation in the following cases: 1) minor local disorder or resistantlateralization of changes in routine EEG; 2) pathological EEG with hy-persynchronization of b or h rhythms, disorganized EEG with absent ordecreased a-rhythm;3) paroxysmal types of EEG in children of any age,even with no pathology in wakeful state.

p227PREVALENCE OF RESTLESS LEGS SYNDROMEAMONG ADULT EPILEPSY PATIENTS IS HIGH: A PRE-LIMINARY SCREENING IN ARMENIAS. Khachatryan*, Y. Tunyan*, L. Ghahramanyan�, andT. Stepanyan�

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*Yerevan State Medical University, Yerevan, Armenia; �SomnusSleep Disorders Clinic, Yerevan, Armenia; and �ErebouniMedical Center, Yerevan, Armenia

Purpose: To perform a preliminary screening of restless legs syndrome(RLS) among adult patients with epilepsy in Armenia.

Method: The screening has been performed among consecutivepatients attending Armenian Republic Epilepsy Center Erebouni.Only adult patients aged 18 and above with definite epilepsy diagno-ses (both de novo and chronic) were included. The four essentialcriteria to diagnose RLS proposed by International RLS Study Group(IRLSSG 2003) have been used by a trained clinician-researcherteam. Only patients positive for all four criteria have been consid-ered to have a clinically significant RLS. Additional brief interviewhas been conducted to exclude other possible mimics of RLS.Assessment of RLS severity and form (idiopathic or symptomatic)was not a purpose of this screening. Descriptive statistics was usedfor evaluation.

Result: Eighty one out of the 93 patients screened had confirmed all-cause epilepsy diagnoses (n = 81). They had 18–64 age interval (meanage – 32.1, 37 females – 45.7%). We found 10 patients fulfilling all 4 cri-teria for RLS (12.3%), and among them 6 males and 4 females (accord-ingly m:f = 60%:40%). RLS in females was 10.8%, and in males –13.6%. Our previous telephone survey (Khachatryan et al. Sleep Medi-cine 2007) showed 7,9% prevalence of RLS in general adult Armenianpopulation and higher prevalence in males.

Conclusion: We found high prevalence of RLS in Armenian epilepsypatients. It was found higher among males. As a sleep restricting and dis-rupting factor, RLS could contribute to difficulties in the management ofepilepsy patients and thus should be screened for carefully.

p228CO-EXISTING PSYCHOGENIC NON-EPILEPTIC SEI-ZURES AND EPILEPTIC SEIZURES: DETERMINATIONOF INCIDENCE IN AN EPILEPSY MONITORING UNITPOPULATIOND. F. Thomas, and A. KrumholzUniversity of Maryland Medical Center, Baltimore, USA

Purpose: It is well described that psychogenic non-epileptic seizures(PNES) and epileptic seizures (ES) may co-exist in the same patient, buthow to best define this co-existence and its incidence are debated.

Method: We reviewed all epilepsy monitoring patients at the Universityof Maryland Medical Center and Veterans Administration Medical Cen-ter Baltimore over an 18 month period to assess the incidence of bothPNES and ES co-existing in the same patient as documented by capturingboth PNES and ES during the same admission. Patients who had morethan one admission were counted only once.

Result: Of our 272 total epilepsy monitoring patients, 172 (63%)were female, and the mean age was 41 years (range 16–88, standarddeviation 14.6). Of the total patients, 74 (27%) had documentedPNES during their admission, and 11 (14.9%) of these PNES patientshad co-existing epileptic seizures determined by video EEG duringthat same admission.

Conclusion: The percentage of co-existing PNES and ES captured onvideo EEG monitoring in our patients (14.6% of all PNES patients) washigher than expected, and may relate in part to more aggressive seizuremedication tapers to provoke events, thereby unmasking more epilepticseizures in our patients. In addition, embellished auras mimicking PNEScannot absolutely be ruled out in a small number of cases. Still, the inci-dence of co-existing PNES and ES in such a high percentage of patientsis notable and suggests that caution is warranted when tapering medica-tion in some patients with PNES.

p229HEALTH-RELATED QUALITY OF LIFE IN PATIENTSWITH EPILEPSY, NON-EPILEPTIC ATTACK DISOR-DER AND DUAL DIAGNOSISF. Ali*, and A. E. Cavanna�

*Birmingham and Solihull Mental Health NHS FoundationTrust, Birmingham, UK; and �Institute of Neurology, London,UK

Purpose: Little is known about the differential impact of epilepsy andnon-epileptic attack disorder to patients’ health-related quality of life(HR-QOL). In this study, we sought to compare self-reported HR-QOLin patients with epilepsy, NEAD and dual diagnosis.

Method: We recruited a total of 66 adult out-patients (n = 17 with adiagnosis of epilepsy, n = 34 with NEAD and n = 15 with a dual diagno-sis) from the specialist Neuropsychiatry Clinic at BSMHFT/Universityof Birmingham. Each participant completed a standardised psychometricbattery which included the Quality of Life in Epilepsy-31 (QOLIE-31).

Result: We found significant differences in cumulative HR-QOL scores(Kruskall-Wallis test, p = 0.041) across the three groups. Patients withdual diagnosis demonstrated poorest HR-QOL ratings (mean=28.4), fol-lowed by NEAD (mean=30.7) and epilepsy (mean=43.5). The most sig-nificant differences were in the Emotional Well-Being domain (p =0.008), where patients with dual diagnosis reported the lowest scores(mean=28.9), followed by NEAD (mean=29.3). Patients with epilepsyreported considerably higher HR-QOL in this domain (mean=45.9).

Conclusion: Patients with a dual diagnosis of epilepsy and NEAD reportpoorest cumulative HR-QOL, with significantly lower scores on Emo-tional Well-Being. Future investigation should be targeted to elucidatecausal links between specific ictal and inter-ictal variables and HR-QOLsubdomains.

p230DISSOCIATIVE EXPERIENCES AND QUALITY OFLIFE IN PATIENTS WITH NON-EPILEPTIC ATTACKDISORDERJ. W. Mitchell, F. Ali, and A. E. CavannaBirmingham and Solihull Mental Health NHS Foundation Trust,Birmingham, UK

Purpose: A wide range of dissociative experiences have been reportedin clinical samples of patients diagnosed with non-epileptic attack disor-der (NEAD). This study investigated the possible impact of dissociativeexperiences on health-related quality of life (QOL) in this patient popula-tion.

Method: In this cross-sectional study we consecutively recruited 37patients (67% female; mean age=44, sd=13.7) with a diagnosis of NEADfrom a specialist neuropsychiatry clinic. Nine patients (24.3%) had con-comitant epilepsy (dual diagnosis). Clinical diagnoses were validated byneuroimaging and neurophysiology findings.

Result: Our sample reported a high level of dissociative experiences,with a mean score of 24.9 (sd=18.2) on the Dissociative ExperiencesScale (DES). We found no significant differences in DES scores betweenpatients with NEAD and patients with a dual diagnosis (Mann-WhitneyU = 117.5, p = 0.884). There was significant negative correlation betweenDES scores and QOL, as measured by the QOLIE-31 inventory (n = 35:Pearson's r=-0.664, p < 0.01). This association remained significant whenaccounting for measures of depression (Beck Depression Inventory,BDI) and anxiety (Spielberger State-Trait Anxiety Inventory, STAI). Amultiple regression analysis model accounted for 73.6% of the variationin total QOLIE-31 scores (n = 33: adjusted R square=0.736). Total DESscores accounted for 52.5% of the variance, whilst the BDI and STAI-trait scores accounted for 16.6% and 4.5%, respectively.

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Conclusion: These findings confirm previous reports of high prevalenceof dissociative experiences in clinical populations with NEAD and high-light the importance of routinely screening patients for these symptoms.The strong association with QOL suggests that patients with NEADwould benefit from treatment interventions targeting dissociation.

p231MUTATIONS WITHIN THE GLRA1 GENE ASSOCI-ATED WITH HYPEREKPLEXIAS. E. Wood*, S. Ali*, C. Drew*, O. W. Howell*, R. H. Thomas�,M. I. Rees*, and S. Chung**Swansea University, Swansea, UK; and �Wales EpilepsyResearch Network, Swansea, UK

Purpose: Hyperekplexia is a paroxysmal neurological disorder causedby defects in glycinergic neurotransmission and is characterized be exag-gerated startle reflexes and hypertonia in response to sudden, unexpectedauditory or tactile stimuli and in some instances, can result in life-threat-ening infantile apnoea episodes. This rare, but potentially fatal, neurolog-ical disorder is associated with mutations in genes encoding the a1(GLRA1) and b (GLRB) subunit of the glycine receptor and the presyn-aptic glycine transporter GlyT2 (SLC6A5).

Method: As part of an ongoing screening program, we have analysedthe entire coding regions of GLRA1 in 66 patients referred to our screen-ing project. All sequence variants identified were regarded as mutationsafter exclusion from a panel of human controls and assessed for proteindamaging outcomes with molecular modelling.

Result: Direct sequencing analysis revealed 15 GLRA1 variants includ-ing 11 non-synonymous changes, 3 nonsense and a recurrent large dele-tion of exon 1 to 6; eight variants identified were novel and not in thepublic domain. Recessive inheritance was revealed in 13 cases, including2 cases of compound heterozygote inheritance, and a dominant inheri-tance in 3 cases. Consistent with previous studies, all deletion and non-sense mutations were associated with recessive onset of phenotype,whereas missense mutations could exert dominant or recessive influencesdepending on the position of the mutation in the polypeptide.

Conclusion: Identification of novel mutations in this study increases thecompendium of GLRA1 mutations in the diagnostic domain for hyper-ekplexia and promote further work into the pathophysiological mecha-nisms underlying the ancient startle response.

p232DEVELOPMENT OF A WAITING LIST INITIATIVEAND IMPLEMENTATION OF AN EARLY INTERVEN-TION CLINIC FOR NON-EPILEPTIC ATTACK DISOR-DERG. M. Fortune, J. A. Magee, and C. BrienBeaumont Hospital, Dublin, Ireland

Purpose: To develop a waiting list initiative and early intervention out-patient clinic for patients with non-epileptic attack disorder to reducewaiting list times and improve access to psychological treatment.

Method: A waiting list analysis was conducted (n-64). An ‘opt-in’ sys-tem was then introduced. Patients who ‘opted-in’ received a 30—minutetriage appointment to review their case and plan towards further interven-tion where necessary. Standardised intake measures and patient satisfac-tion data were obtained.

Result: Following waiting list analysis, 47 patients were entered into the‘opt-in’ system. Those patients who opted in, all received a triageappointment resulting in a treatment contract or a discharge to local ser-vices. Following an invitation to ‘opt-in’, 18 patients actively declined to

be placed on the new waiting list. 10 patients passively declined to beplaced on the waiting list due to non-responding. A total of 19 patientsrequested a triage appointment. Of these, patients, 7 were assessed anddischarged, 6 were assessed and a treatment plan was formulated and 6were reviewed and referred to local mental health services with a reviewplanned.

Conclusion: The development of this waiting list initiative and triageclinic has resulted in a reduction in waiting list size. Furthermore,patients who are referred to this clinic now receive an initial appointmentwithin three months following inpatient review. Results will be discussedwith respect to the pro's and con's of approaches to waiting list manage-ment.


p233A RETROSPECTIVE STUDY OF 131 PATIENTS WITHPSYCHOGENIC NON-EPILEPTIC SEIZURES (PNES):COMORBID DIAGNOSES AND OUTCOME AFTER IN-PATIENT TREATMENTH. C. Miersch, K. Bohlmann, and H. StraubEpilepsieklinik Tabor, Bernau, Germany

Purpose: This retrospective study analyses the comorbid diagnoses ofpatients with psychogenic non-epileptic seizures (PNES) and the out-come after in-patient treatment including cognitive behavioural therapy,family therapy and non-verbal therapies.

Method: Within 7 years 377 in-patients were treated in the departmentfor epileptology and psychotherapy of the Epilepsiezentrum Berlin-Bran-denburg. 131 patients were diagnosed with PNES. All diagnoses reportedat the time of discharge were reviewed. Follow-up interviews of 111patients were made within 6 months after discharge.

Result: Comorbid somatic diagnoses were found in 42 patients. 64%were related to the brain. Concomitant epilepsy was confirmed in 31patients. Comorbid psychiatric diagnoses were anxiety disorders (47),personality disorders (41), posttraumatic stress disorder (39), substanceabuse(14), depressive disorders (11), somatoform disorders (6), bipolardisorder (5), factitious disorder (4), Asperger syndrome (3) . Psychic trau-mas were found in the history of nearly all patients. Sexual assault wasreported by 28 patients and strongly suspected for another 21 patients. 89patients complained about massive and long running conflicts withintheir families. After in-patient treatment 57 patients remained free of sei-zures. 36 patients had less frequent seizures, 17 were unchanged, 1 hadcommitted suicide.

Conclusion: In-patient treatment including intensive psychotherapy andadditional non-verbal therapies in a clinic with an expertise in epileptolo-gy, psychiatry and psychotherapy is successful for nearly 3/4 of patientswith PNES. Beside sexual assault 68% of the patients with PNESreported severe and longlasting conflicts in the family causing psycho-logical distress. This confirms the importance of family therapy besidescognitive behavioural therapy.

p234SIGNIFICANCE OF ACTIVATION OF AURAS INPATIENTS WITH PSYCHOGENIC NON-EPILEPTICSEIZURES (PNES)K. N. Ramesha, A. Ribeiro, D. Amin, and F. BrunnhuberKings College Hospital, London, UK

Purpose: To evaluate the significance of activation of habitual auras inthe activation clinic in patients with suspected PNES.

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Method: We studied consecutive 105 patients, confirmed to have PNESin our activation clinic over the last five years. The diagnosis of PNESwas made based on electro-clinical features of the recorded event(s).They were confirmed to be habitual by patients and/or their eyewit-nesses.

Result: The mean duration of PNES before the activation clinic was 9.7years (range: 1–56 years). Suggestions alone brought out habitual PNESin five patients, photic stimulation alone was used as an induction proce-dure in 49 and combination of photic stimulation and hyperventilationwas used in another 20 patients. No active activation procedure was per-formed in 15 patients and various combinations of the above procedureswere used in the remaining. 41 patients reported their habitual aura in theactivation clinic. They were epigastric aura (n = 6), olfactory aura (n = 2),gustatory aura (n = 4), visual aura (n = 1), auditory (n = 2), sensory (n = 5)and nonspecific auras (n = 23). No statistically significant correlationwas noted between the presence of aura and duration of PNES.

Conclusion: Auras that are commonly regarded as ‘epileptic auras’ dooccur as dissociative auras in PNES during activation and thus do notimply the coexistence of epilepsy. Activation of ‘epileptic auras’ in theactivation clinic appears to be a strong point in favour of the diagnosis ofPNES.

p235USE OF ANTI-EPILEPTIC DRUGS IN THE SETTING OFNON-EPILEPTIC SEIZURESM. Stefanidou, S. Nadkarni, and C. CarlsonNew York University, New York, USA

Purpose: Non-epileptic seizures (NES) without concurrent epilepsyaccount for about 10% of patients evaluated in epilepsy monitoring units.Many of these patients are on anti-epileptic drugs (AEDs) upon admis-sion for their events and/or co-morbid psychiatric and pain disorders. Weevaluated if presence of AEDs at the time of diagnosis of NES affectstheir long term exposure to these agents, given concerns of unnecessaryuse of AEDs in this patient population.

Method: A retrospective review of all admissions to the epilepsy moni-toring unit at NYU for 2010 was conducted. Inclusion criteria requiredcapturing the targeted event and a normal video-EEG. AEDs and otherpsychotropic agents were recorded upon initial admission, discharge, andat follow up.

Result: Of 900 patients, 75 (8%) patients were diagnosed with NES with44 (60%) on AEDs upon admission. The most prevalent co-morbid psy-chiatric conditions were anxiety, mood and panic disorders without sig-nificant difference between patients on or off AEDs at admission (p =0.73). AED use at admission correlated with higher use of AEDs at dis-charge (p = 0.0001). 70% of patients had outpatient follow-up. Patientson AEDs at admission were more likely to be on AEDs at follow-up (p =0.0001) and use these agents for treatment of concurrent psychiatric and/or pain conditions (p = 0.02).

Conclusion: Presence of AEDs upon admission for evaluation of NESincreases probability of long term exposure to AEDs. Although this studydoes not compare clinical outcomes, it suggests a possible benefit fromearly evaluation of events prior to the initiation of AEDs in patients withhigh suspicion for NES.

p236CLINICAL AND LONG-TERM VIDEOEEG FEATURESOF PATIENTS WITH BOTH PSYCHOGENIC NON EPI-LEPTIC AND EPILEPTIC SEIZURES: A PROSPECTIVESTUDY IN A SPANISH EPILEPSY UNITR. M. Vivanco-Hidalgo, J. Jimenez-Conde, A. Massot,J. Herraiz, C. Garcia-Ribera, J. Roquer, and R. RocamoraParc de Salut Mar-Hospital de Mar, Barcelona, Spain

Purpose: Both epileptic seizures (ES) and psychogenic non epilepticseizures (PNES) can coexist in the same patient. According to publisheddata, between 8 and 60% of patients with PNES also can have ES. Long-term videoEEG (LTVE) is the diagnostic tool used to differentiate them.But it is not well established how long LTVE should be to make a properdiagnosis in these cases.

Objetive: To describe clinical and LTVE features in patients with bothES and PNES admitted in Epilepsy Unit (EU) and estimate LTVE dura-tion to make diagnosis.

Method: We reviewed LTVE, medical history and complementary testsin 94 adult patients admitted in our EU between 2010 and 2011. Wedivided them into 3 groups: patients with only ES, only PNES and bothES+PNES. We compared them. All the episodes were checked with thefamily.

Result: 84 patients had seizures. 62 had only ES, 16 PNES and 6 bothES+PNES. Non statistically significant differences were found betweentime of appearance (TOA) (days) of PNES and ES groups, median 2 (1–3) vs 3 (1–4), p 0.63. In ES+PNES group, ES TOA was 3.5 (2,5–4,25) vsPNES 2 (1,75–3,25). All patients in ES+PNES group had PNES first.83.3% of them had the first ES after the second day. In our study, 27%with PNES had also ES. Patients with both ES+PNES had first PNES dur-ing monitoring. An early monitoring disruption could lead to a misdiag-nosis in this group. A prolonged LTVE (>72 hours) to record bothepisodes is justified and necessary to make a correct diagnosis.

p237‘‘RINCH MOTIONS’’ (RHYTHMIC ICTAL NONCLONICHAND MOTIONS) ANALYSIS: INCIDENCE AND LAT-ERALIZING VALUEK. Musilov�*, R. Kuba*, N. M. Vojvodic�, M. Br�zdil�,I. Tyrlikova§, and I. Rektor�

*Brno Epilepsy Centre – St. Anne's University Hospital andFaculty of Medicine, Brno, Czech Republic; �Clinic ofNeurology Clinical Center of Serbia, University of BelgradeSchool of Medicine, Belgrade, Serbia; �Epilepsy Center Brno,St. Anne's University Hospital and Faculty of Medicine, MasarykUniversity, Brno, Czech Republic, Brno; and §St. Anne'sUniversity Hospital and Faculty of Medicine, MasarykUniverzity, Brno, Czech Republic

Purpose: The principal aim of this retrospective study was to analyseoccurrence and lateralizing value of Rhythmic Ictal Nonclonic Hand(RINCH) motions symptom in temporal lobe epilepsy with hippocampalsclerosis (TLE-HS) or with other lesion of temporal lobe (TLE-oth) inour group of patients.

Method: Retrospectively, we analysed 120 patients with temporal lobeepilepsy (TLE). All patients were classified as Engel I at the 2—year fol-low-up visit. Histopathological examination revealed hippocampal scle-rosis (TLE-HS) in 70 patients and other lesions in 45 patients (TLE-oth);5 patients had no lesions. We reviewed 491 seizures. RINCH motionswere defined as unilateral, rhythmic, nonclonic motions occurring duringthe seizure, sometimes in the relation to the dystonic posturing of thehand on the same side.

Result: RINCH motions were observed in 24 of 120 patients (20%), andin 48 of 491 seizures (9.8%). There was no significant difference betweenoccurrence of RINCH motions in patients with TLE-HS and in patientswith TLE-oth (21.4% vs. 18%). RINCH motions were contralateral to theseizure onset in 83.3% of patients, and in 91.7% of seizures. RINCHmotions were more frequent in patients with left- than right-sided TLE(68.63% vs. 31.37%) and they were associated with dystonic posturingon the affected side in 33.33%. There were no differences in lateralizingvalue of RINCH motions between patients with TLE-HS and TLE-oth.

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Conclusion: RINCH motions symptom is a relatively frequent ictal signin patients with TLE. The side of RINCH motions in patients with TLElateralizes the seizure onset to the contralateral temporal lobe.

Aknowledgements: This work was supported by MSMT CR researchproject MSM0021622404.

p238WHAT ABOUT A TRANSITION PROGRAM ON EPI-LEPSY?J. Carrizosa, and T. RodriguezUniversity of Antioquia, Medell�n, Colombia

Purpose: Transition from a family to an individual centered service,could carry troubles for persons with chronic diseases. General guidelinesfrom IBE and ILAE are lacking. The purpose is to built up a transitionreference guideline for persons with epilepsy.

Method: Literature review; questionnaires on transition during the VILatin American Congress in Cartagena. Framework on goals and key top-ics.

Result: Goals: 1. Preparing adolescents and young adults for transfer ofcare 2. To provide uninterrupted health care 3. Education on specific andindividual issues 4. To promote self advocacy skills and independence 5.To optimize quality of life, life expectancy and future productivity. Keypoints: 1. Timing of transition and transfer 2. Family Dynamics 3. HealthSupervision Issues 4. Anticipatory Guidance 5. Sexuality, ReproductiveIssues and Pregnancy 6. Genetic Counseling 7. Education and DegreeChoices 8. Physical Activity Sports 9. Driver¢s Licence 10. Mortality 11.Psychiatric Aspects 12. Medical Social Insurances.

Conclusion: A transition program, with prepared communicationbetween pediatric -adolescent and adult health services, could foster abetter quality of life in persons with epilepsy.

p239A REVIEW OF AN EPILEPSY NURSE SPECIALIST'SCLINICAL ACTIVITY & ASSOCIATION WITH PAEDI-ATRIC EPILEPSY ADMISSIONSK. Johnson*, and C. Dunkley�

*Kings Mill Hospital, Nottinghamshire, UK; and �SherwoodForest Hospitals, Sutton in Ashfield, UK

Purpose: To quantify and characterise clinical activity for the ENS overtime and to assess whether the introduction of an ENS is associated witha change in paediatric epilepsy admission rates.

Method: A prospective review of the ENS diary was undertaken docu-menting all client contact. Activity was collated comparing the types ofclient contact over a 4 year period 2007–2011. Local admission rates ofchildren with epilepsy were also obtained using the Child and MaternalHealth Observatory (CHIMAT) Data Atlas which maps Hospital EpisodeStatistics (HES) data to geographical areas.

Result: The prospective diary review showed a yearly median of 29ward visits; 2 Emergency Department visits, 35 home visits; 560 tele-phone contacts; 15 Buccal Midazolam training sessions and 32 ad-hocpaediatric outpatient reviews, Each year there was a median of 22 multi-disciplinary epilepsy clinics; 19 nurse led clinics; 4 paediatric neurologyclinics and 71 school visits. Mean admission rates over 3 years before theESN commenced were 67/100,000 children/year (range 62–72.1). Meanrates over 3 years after ESN commencement were 35.2/100,000 children/year (range 32.3–37.5).

Conclusion: The diary review clearly shows the diversity of the ENSactivity and how this has changed over time. Ward visits have reduced

coinciding with reduced epilepsy admissions. Outpatient interventionshave increased. The number of telephone contacts have more than dou-bled in the second year, appearing static in years three and four. Educa-tional and supportive visits to the child's home and school have alsoincreased. Activities of an ESN changes over time towards non-admis-sion and community-based activity.

p240IMPLEMENTING THE AMERICAN ACADEMY OFNEUROLOGY EPILEPSY QUALITY MEASURES –USING AN EPILEPSY ELECTRONIC PATIENTRECORD AS A TOOL FOR CHANGEM. Fitzsimons, B. Dunleavy, P. O’Byrne, and N. DelantyBeaumont Hospital, Dublin 9, Ireland

Purpose: The American Academy of Neurology (AAN) quality indica-tors for epilepsy care describe the tasks that should be performed during apatient encounter and specify details to be documented in the medicalrecord. With these, quality of epilepsy care can be monitored, gaps identi-fied and ultimately improvements made.

Aim: An epilepsy electronic patient record (EPR) was used to implementAAN quality indicators to assess performance of an out-patient service.

Method: A sample of out-patient clinics at Beaumont Hospital, Dublinwas assessed. The epilepsy EPR was examined to determine if it sup-ported the capture of data relevant to four AAN indicators of interest.Using a specialised database query language, structured and unstructureddata fields were interrogated to generate the numerator and denominatorfor the indicators.

Result: Over a sample of 5 weekly out-patient clinics there were 161individual patient encounters. Of these 87% (142/161) conformed withthe requirement to document seizure type and seizure frequency at eachvisit (indicator 1); etiology or epilepsy syndrome was documented/updated for 57% (93/161) (indicator 2); evidence of querying and coun-selling about anit-epileptic drug side-effects for that encounter was pres-ent in 30% (49/161) of records. Over a 1 year period, counselling forwomen of childbearing potential (indicator 8) was present in 30% (102/346) records.

Conclusion: Feasibility of the epilepsy EPR for efficient performancemonitoring was demonstrated. Results indicate either failure to carryoutrecommended clinical tasks or poor documentation. Whichever is thecase, a baseline is provided against which improvement goals can be set.

p241TRANSITION'S GAP FROM PAEDIATRIC TO ADULTSYSTEM CARE OF PATIENTS WITH EPILEPTICENCEPHALOPATHY: A MYTH OR A REALITY?M. Kuchenbuch*, N. Chemaly*, C. Chiron�, O. Dulac*, andR. Nabbout�

*Necker, Paris Cedex 15, France; and �Inserm, Paris, France

Purpose: In order to understand the reality of a transition gap betweenpediatric and adult care system in patients with epileptic encephalopathy,we compared medical care between childhood and adulthood with adetailed description of factors that impacted the transition in a cohort ofpatients with Dravet syndrome.

Method: 52 surveys realized by a group of experts with help of IPSOSinstitute and Wyeth foundation were filled by patients and families withDravet syndrome, aged over 18 years. Student t-tests and fisher exact testswere used. After validity conditions verification, we compared the experi-ence of patients and their family in paediatric versus adult care systemand then we studied the factors that impacted the quality of transition.

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Result: Sixty one percent had a transition and 92% of them noted thatthere wasn't any gap during their transition to adult care. Factors that posi-tively impacted their transition were the transition preparation quality(p<.000001), longer duration of follow-up in the same pediatric structure(p<.001), good availability of the pediatric staff (p<.01), age over 18 yearsat transition (p<.01) and good health's condition before transition (p<.05).All families had a positive experience in paediatric health system. Paedia-tricians were considered as welcoming, taking time to explain and help-ing. Contrarily to the impression of child neurologist, the adult caresystem experience was identical and showed no statistical difference.

Conclusion: Transition in Dravet's syndrome showed a lack of gapbetween pediatric and adult care health system.

p242AUDIT OF PATIENT SATISFACTION AT THE TRANSI-TION ADOLESCENT EPILEPSY CLINIC IN THE WAL-TON CENTRE NHS FOUNDATION TRUST, LIVERPOOLM. Rodriguez*, T. Marson*, and R. E. Appleton�

*Walton Centre for Neurology and Neurosurgery NHSFoundation Trust, Liverpool, UK; and �Alder Hey Children'sHospital, Liverpool, UK

Purpose: We assess the satisfaction of patients attending the TransitionAdolescent Epilepsy Clinic at the Walton Centre, a monthly clinic runjointly by an adult and a paediatric neurologist.

Method: A Patient Satisfaction Questionnaire was sent to 108 patients(new or follow up) who attended the clinic between March 2009 and Sep-tember 2010.

Result: Questionnaires were returned by 30 patients (response rate27%), 16 were female, age range 18–22. 11 had focal, 4 generalized and4 unclassified epilepsy. 21 had experienced seizures within the preceding12 months. 29 patients were receiving an antiepileptic drug, of whom 15were on monotherapy. Regarding the handover, 53% stated that theywere told what to expect when they attended the clinic. Regarding clinicappointment, 87% found the waiting area pleasant, 87% felt the clinicappointment met their expectations, 80% had an opportunity to voicetheir own opinion, 50% felt all their questions were answered with 33%stating most questions were answered. 50% were provided with writteninformation and found it useful. 17% would like to have been seen with-out their parents. 27% had phoned the epilepsy nurse. Regarding appoint-ment number, 70% feel they have the right number, 20% too few, 7% toomany. Regarding time spent in clinic, 83% think it was enough, 10% toolittle.

Conclusion: The response rate was low highlighting the difficultyengaging with teenagers. Respondents indicate a high level of satisfac-tion with the service, but there is room for improvement including provi-sion of better information about the service and improving theenvironment.


p243LEARNING ENVIRONMENT AT A PAEDIATRIC WARD– A QUALITATIVE STUDYT. LøvenskjoldDanish Epilepsy Center, Dianalund, Denmark

Purpose: At the paediatric department at Danish Epilepsy Centerpatient education given to children and parents is an important part of

the hospitalization. For over 10 years, there has been a patient educa-tion program primarily for parents at the department. The teachinghas been organized from a commonsense approach without any genu-ine formalized educational goals, and without any proven pedagogicalapproach to learning. In order prospectively to reinforce patient edu-cation in the department, this project started August 2011 and will beconcluded in August 2014.

Method: The study is a combination of observation and interview stud-ies where interviews are conducted with teachers, parents, children in apediatric ward in Denmark and Norway. The purpose of the study is tocompare the learning environment in Denmark and Norway.

Result: Aim: To explore how children learn mastering the everyday lifewith epilepsy during hospitalization. The project deals with children withepilepsy and there learning processes during hospitalization. The projecttakes a broad life history as well as cultural and social view on the learn-ing processes. Parents have a central role in patient education at the ward,and the purpose of the study is to bring an analytical look at the learningenvironment, understood as the interaction between the department, tea-cher and patient.

Conclusion: Research questions: How do children learn to live with epi-lepsy with all its consequences for the individual's everyday life? Whichlearning processes imply the everyday life with epilepsy and in whichway does it appear in the learning environments at the paediatric depart-ment?

p244CAN A NURSE INTERVENTION PROMOTE THE SELF-MANAGEMENT OF PATIENTS WHO ATTEND EMER-GENCY DEPARTMENTS WITH ESTABLISHED EPI-LEPSY? A NESTED QUALITATIVE STUDYA. J. Noble*, C. Virdi�, M. Morgan�, and L. Ridsdale�

*Institute of Psychiatry, King's College London, 8AF, UK;�Department of Clinical Neuroscience, London, UK; and�King's College London, London, UK

Purpose: People with epilepsy (PWE) frequently attend emergencydepartments (EDs). Attendance is associated with AED non-adherence,low knowledge of epilepsy and stigma. Reducing unnecessary emer-gency hospitalisations could help patients and reduce costs. We are con-ducting a trial aimed to reduce epilepsy ED visits, by a self-managementintervention with an epilepsy nurse-specialist (ENS). We here describepatients’ perceptions of acceptability and benefits.

Method: N = 85 adults with epilepsy were prospectively recruited from3 London EDs. The first 20 (age=41, SD=17; 10 males; median yearssince diagnosis=12) receiving the intervention were invited for semi-structured interview. Transcripts were analysed thematically.

Result: Participants reported not having been previously confident inmanaging their epilepsy, but that the intervention improved this. It didthis by meeting a need for information on epilepsy, with the ENS being‘‘available in a way GPs and consultants are not’’: Responses included:‘‘It was the first time someone had sat down and really told me a hugeamount’’; ‘‘she took the time to go through my needs’’, ‘‘you felt youcould ask questions, not that wasting her time’’. Patients felt ‘‘not sofrightened’’ of seizures. One said ‘‘I don't feel as if I now need to go tohospital every time’’. Learning about epilepsy prevalence helped patientsnot ‘‘feel so alone’’ and ‘‘less ashamed’’. They also felt AED adherenceimproved.

Conclusion: This short intervention was acceptable to PWE whoattended ED. It satisfied a perceived need for information and in turnincreased confidence. We will report whether the intervention leads toreduced ED use subsequently.

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p245FACILITY OF EPILEPSY SERVICE IN THAILANDS. Towanabut*, S. Tiamkao�, and S. Pranboon�

*Prasat Neurological Institute, Bangkok, Thailand; and �

Integrated Epilepsy Research Group, Khon Kaen University,Khon Kaen, Thailand

Purpose: This study was aimed at investigating the readiness of epilepsyservices in Thailand.

Method: The data was collected through questionnaires sent out to1,033 public hospitals all over the country on their readiness in providingservices to epileptic patients. 559 hospitals returned the questionnaires(54.11%). The data was then analyzed in percentages.

Result: The results show that most epileptic doctors are general practi-tioners (30.4%). Epileptic specialists and neurologists account only for11.1 and 14.4%, respectively. There are altogether 52 EEGs, 54 CT Scan-ners, and 6 MRIs. Four main types of antiepileptic drugs are prescribed topatients, namely, Phenobarbital, Phenytoin, Carbamazepine, and Valpro-ic acid, at 99.9, 96.0, 97.9, and 89%, respectively. New antiepilepticdrugs include Gabapentin, Topiramate, Levetiracetam, Lamotrigine, andPregabalin (77.6, 63.9, 46.0, 45.3, and 33.6%, respectively). Vigabatinand Oxcarbazepine accounted for only 14.5 and 14.3%. Intravenous anti-convulsants used for status epilepticus patients include Phenytoin(54.2%), Gardinal sodium (33.9%), and Sodium valproate (12.1%). Only45.7% of therapeutic drug monitoring can be done.

Conclusion: There is still a limitation in the readiness of services in pub-lic hospitals. This is primarily due to a lack of doctors who specialize intreating epilepsy. Hospitals also lack diagnostic tools for antiepilepticsand therapeutic drug monitoring. Therefore, a study needs to be con-ducted to develop a prototype model for epileptic treatment that is appro-priate to the constraints and conditions of our country.

p246IMPACT OF STAFFING LEVELS AND TRAINING ONPATIENT SAFETY & MANAGEMENT ON THE EPI-LEPSY MONITORING UNITC. A. Mclaughlin*, M. C. Walker�, B. Diehl�, C. Scott*,T. Wehner*, and C. Milabo**The National Hospital for Neurology and Neurosurgery,London, UK; �Department of Clinical and ExperimentalEpilepsy, London, UK; and �UCL Institute of Neurology,London, UK

Purpose: This audit aimed to assess the impact of changes to staffinglevels, protocols and training on ictal and postictal management andinterview in the Epilepsy monitoring Unit.

Method: We carried out a retrospective analysis reviewing Video-EEGdata and reports from Jan-Feb 2011 and compared findings to an earlierstudy. Since 2002 core nursing staff had been increased by 50%, a wardsister added and bed capacity increased. Speed of seizure attendance, caregiven, proportion of unrecognised seizures and seizure type were consid-ered. Up to 5 seizures per extracranial pre-surgical patient were included.Seizures with subjective symptoms & no clear clinical change wereexcluded, giving a total of 90 seizures in 30 patients.

Result: Significantly more seizures were attended in 2011 than 2002(77% versus 59%, P < 0.05 Chi Square). There was also a non-signifi-cant tendency for a faster response time: median 28 s (range 0–240s)in 2011 c/w 41s (range 0–600s) in 2002 (P = 0.2 for difference, Mann-Whitney U test). Cot sides were more likely to be up during all sei-zures (81% in 2011 c/w 35% in 2002, P < 0.001) and this was particu-larly evident in tonic-clonic seizures (15/16 in 2011 versus 0/4 2002, P= 0.001 Fisher's Exact).

Conclusion: The introduction of a strict protocol for pre-surgicalpatients leaving their room, usage of cot sides and a higher staff to patientratio with increased training has made this Epilepsy Monitoring Unitmore productive with a safer environment for those undergoing pre-sur-gical assessment. This study emphasises the benefit of staff training andtelemetry protocols.

p247NATIONAL AUDIT OF SEIZURE MANAGEMENT INHOSPITALS: INITIAL FINDINGSA. G. Marson*, P. Dixon*, M. Pearson�, J. Kirkham*, andK. Billington**University of Liverpool, Liverpool, UK; and �UniversityHospital Aintree, Liverpool

Purpose: Little is known about the organisation and delivery of epilepsycare in the UK. The National Audit of Seizure management in Hospitals(NASH) is the first comprehensive UK-wide epilepsy audit.

Method: NASH assessed the immediate care, onward care pathwaysand prior care of patients attending Emergency Departments with sei-zures. Sites provided anonymous data on 30 consecutive cases via abespoke web-based database.

Result: Data were collected from over 3750 patients across 127 sites inthe UK (mean age = 45.8 (SD 19.9), 57% male). 67% of the patients hadestablished epilepsy whilst 18% presented as a result of their first seizure.Results show considerable variability, with a few sites performing welldemonstrating that good care is possible. But overall, assessment on arri-val was inadequate, routine measurements were not done (temperature inonly 83% of patients), a proper neurological examination with plantarresponses recorded in 37% (IQR 20.0 – 49.1), an attempt to gain an eye-witness description in 58% (IQR 43.3 – 73.3), and an ECG performed in59% (IQR 43.3 – 75.8). It was not routine in most hospitals to ask patientswho have had a seizure about driving – despite the obvious road safetyimplications for themselves and others. Only 51% of first seizure patientswere referred for any form of neurology specialist assessment.

Conclusion: Basic care currently provided shows wide variability andin many centres is inadequate to achieve good patient outcomes. Neurolo-gists and epileptologists have to engage with acute services to improvethis.

I can confirm that none of the authors for the abstract I submitted haveconflicts of interest.

p248AMBUFLEX/EPILEPSY – IMPLEMENTATION OFPATIENT-REPORTED OUTCOMES IN EPILEPSY CLIN-ICSL. M. V. Schougaard*, P. Sidenius�, J. Christensen�,L. Overbeck�, B. J. Hanner�, and N. H. Hjollund�

*Regional Hospital West Jutland, Herning, Denmark; and�Aarhus University Hospital, Aarhus C, Denmark

Purpose: Patient-reported outcomes (PRO) are commonly used in clini-cal trials and observational studies. However, use of PRO in clinical prac-tice is rare but may have several advantages. AmbuFlex is a web-basedquestionnaire system that implements PRO in the clinical decision mak-ing. Implementation of AmbuFlex for epilepsy involves several issuesincluding disease related questions, setting and frequency of assessment,presentation of results and evaluation of the effect on the organization ofpatient care. Purpose:

To implement AmbuFlex in 3 epilepsy outpatient clinics in Jutland,Denmark and thereby provide the patients with a more flexible care,improve; quality of treatment, patient self-management and utilization ofresources in the health care system.

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Method: The target group was all patients with epilepsy (n G 6500)associated with the 3 outpatient clinics. Three clinical expert groups wereinvolved in the development of the epilepsy-questionnaire, which wastested on 20 epilepsy outpatients. Patients could choose to respond ineither web or paper form. The results of the questionnaire were presentedgraphically for the clinicians within the individual, electronic medicalrecords.

Result: The pilot study provided useful information and apart fromsome problems due to recall bias and linguistic skills, most outpatientsfound the questionnaire easy to use. Patient referral to AmbuFlex is ongo-ing and the aim is to include the majority of patients associated with the 3outpatient clinics.

Conclusion: The results suggest that AmbuFlex is a flexible assessmentprogram that may improve care for persons with epilepsy and optimizethe use of resources in the health care system.

p249EPILEPSY CARE BY RAIL IN RURAL INDIA – THINK-ING OUT OF THE BOX!M. B. Singh, R. Bhatia, M. Padma, M. Tripathi, and K. PrasadAll India Institute of Medical Sciences, New Delhi, India

Purpose: To explore the possibility of a mobile clinic on the LifelineExpress using India's vast railroad network for spreading epilepsy aware-ness and conducting epilepsy screening clinics in remote, underservedparts of rural India.

Method: The Lifeline Express arrives and stays at a new destinationevery month. We have organized a 2–3 day epilepsy clinic at each of its’stops over the last 2.5 years. The epilepsy clinic screens patients whocome in response to an extensive door-to-door campaign urging them toavail free services. Patients are interviewed, examined clinically, given aprescription and advised to follow-up and continue regular treatment.Epilepsy awareness activities amongst school children and teachers, andvillagers are also carried out at each stop.

Result: At Morena in the Central Indian state of Bihar, 144 patients (96male) were examined on the LLE. The mean age was 24.7 years. A fam-ily history of epilepsy was present in 22.9% of the patients and a neuro-logical deficit in 11.8%. A seizure frequency of at least 1/day, 1/week, 1/month, 1/year or rarer was present in 15.7, 10.4, 58.3, 10.4 and 5.2 per-cent of patients respectively. Only 20.8% of the patients had ever beeninvestigated with CT/MRI and 17.4% with an EEG. Patients who hadnever been treated with any AED were 37.5%

Conclusion: Epilepsy treatment gap of >90% is reported from manyparts of rural India. Innovative means of delivering epilepsy servicescombined with an emphasis on increasing epilepsy awareness are neededurgently. The Indian railways with its’ wide rural reach holds promise.

p250THE DEVELOPMENT OF STANDARD OPERATINGPROCEDURES (SOPS) IN EPILEPSY CARE TO REDUCEVARIABILITY AND TRANSFORM A NATIONAL SER-VICE. NATIONAL EPILEPSY CARE PROGRAMME,(NECP) DIRECTORATE OF CLINICAL STRATEGYAND PROGRAMMES, HEALTH SERVICE EXECUTIVE,DR. STEEVENS HOSPITAL, DUBLIN, IRELAND.ROYAL COLLEGE OF PHYSICIANS, DUBLIN, IRE-LAND. CHANGE MANAGEMENT TRAININGM. E. White*, M. Harris�, M. White�, S. Morrow§, andC. Doherty*

*HSE Dr Steevens Hospital, 8, Ireland; �Change ManagementTraining, 8, Ireland; �HSE, 8, Ireland; and §RCPI, 2, Ireland

Purpose: There is considerable variation in the provision and deliv-ery of epilepsy care worldwide. Variation is at the root of disparitiesin quality, safety, access and value. In aviation, standard operatingprocedures (SOPs) are the distilled wisdom of professionals plus sci-entific evidence and have been developed over the last 3 decades,resulting in unparalleled quality and safety achievements. Healthcareis more complex than other industries but the use of SOPs, particu-larly by medical staff is rare.

Method: In July 2011 the NECP in Ireland began a process of SOPdevelopment. Key clinical staff, patients and carers were invited to aprofessionally mediated workshop to determine key elements of excel-lence in epilepsy care covering ambulatory and acute care, diagnos-tics, therapeutics and prolonged Video-EEG monitoring units. Overthe next 6 months, smaller groups met for 4–5 sessions to develop theSOPs.

Result: 45 SOPs were developed which were put in a standardizedHealth Services Executive format. Twelve priority SOPs covering thethree most important initial processes under each heading were endorsedby the clinical advisory group in Dec 2011 . All draft SOPs were postedin draft form on line in the spring on 2012 ready for small ‘Plan, Do,Study, Act’ trials.

Conclusion: The increasing complexity of modern healthcare demandsthat standardized procedures to reduce variation are required which willlead to improvements in quality, safety and cost. The NECP has devel-oped 45 draft SOPs for improving epilepsy care that can act as templatesfor other national services.

p251LATE-LIFE REMISSION IN INTRACTABLE EPILEPSY:‘‘BURNT OUT EPILEPSY’’ OR NATURAL HISTORY?M. Belluzzo*, J. Novy�, G. Bell�, M. Koepp�, S. M. Sisodiya�, andJ. W. Sander�

*University of Trieste, Cattinara Hospital, Trieste, Italy; and�UCL Institute of Neurology, London, UK

Purpose: Terminal seizure freedom in people with epilepsy is com-monly considered an unlikely event if this is not reached in the earlystages of the condition. In a subset of elderly people with long-standingrefractory epilepsy, we aimed to see whether spontaneous remission canoccur despite a life-long history of continuous seizures.

Method: We carried out a retrospective evaluation of seizures patternsamongst people with longstanding pharmacoresistant epilepsy, institu-tionalized at the Epilepsy Society Chalfont Centre and who died between1988 and 2009.

Result: Among 122 people who had epilepsy for longer than 10 years,26 (21%) reached a late, sustained remission (more than two years of sei-zure freedom). Seizure remission occurred at median age of 71 years andthe median duration of seizure freedom was 6 years. Onset of remissionwas unrelated to medication changes in the vast majority of cases (92%).People who had experienced a previous interval of remission were morelikely to be in remission at the time of death (p = 0.004, chi2). The lengthof the terminal remission was similar to that of previous remissions (p =0.128, t test), but end of life remissions were more frequently spontane-ous (p = 0.0016, Fisher exact test). Multivariate analysis suggests thatolder age at death was the only variable directly linked to the likelihoodof late remission.

Conclusion: Our study provides some preliminary evidence that forsome people with epilepsy there is a natural tendency for seizures to stopwith advancing age.

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p252COMPARATION OF PROGNOSIS BETWEENPATIENTS WITH AND WITHOUT EPILEPTIC SEI-ZURES AS A FIRST MANIFESTATION OF STROKES. Z. AticHospital for Cerebrovascular Diseases Sveti Sava, Belgrade,Serbia

Purpose: Epileptic seizure is very often present as a first manifestationof stroke. The aim of our study was to compare the prognosis betweenpatients with and without epileptic seizures as a first manifestation ofstroke.

Method: We studied patients with acute stroke admitted to our hospi-tal during the same period, using a standard protocol including atleast one MR/CT scan, electroencephalography (EEG) and neurologi-cal examinations. The patients were divided into the two groups:1.study group with epileptic seizures as a first manifestation of acutestroke 2. control group with acute stroke and without epileptic sei-zures. All of those patients were analyzed within 3,6,9 and 12 monthsof stroke.

Result: 104 patients with acute stroke were attended,46 female and 58male, age range 39 to 83.48 were observed in the study group and 56in the control group. After 3 months 5/48 patients from the study groupand 3/56 from the control group had died. After 6 and 9 months 40patients(15 from the study and 25 from the control group) were notavailable, but 12 from the study group and 5 from the control grouphad died. After 12 months of follow-up 15 patients were hospitalizedagain.10 of those have had a repetitive or the first epileptic seizuresbut without acute stroke.

Conclusion: We did not find significant differences in prognosisbetween all patients after 3 and 6 months, but increased mortality after 9and 12 months of follow-up. The frequncies of repetitive seizures andmortality were higher between patients with previous seizures, but alsodepend of type of stroke.


p253SURGICAL VERSUS CONSERVATIVE TREATMENT INPATIENTS WITH CEREBRAL CAVERNOMAS ANDNON REFRACTORY EPILEPSYS. Fern�ndez*, J. Mir��, M. Falip�, G. Plans�, S. Castanyer�,A. Fern�ndez-Coello�, and J. J. Acebes�

*Hospital Plat�, Barcelona, Spain; and �Hospital Universitaride Bellvitge, L¢Hospitalet de Llobregat, Spain

Purpose: Patients with cerebral cavernomas often presents with sei-zures. It is still unclear if surgery is the optimal approximation in patientswith cavernomas and new onset epilepsy, sporadic seizures or non wellestablished refractory epilepsy. The aim of this study was to compare theseizure frequency of patients with cerebral cavernomas operated and nonoperated, in order to obtain more information to the correct managementof these patients.

Method: We studied retrospectively 43 patients with non refractory epi-lepsy secondary to cerebral cavernoma. 26 patients (60.5%) underwentsurgery and made up the surgical group, and 17 patients were treatedmedically and constituted the medical group. Seizure frequency, need ofantiepileptic drugs post-treatment and other clinical variables were com-pared between both groups.

Result: At two years, in the surgical group there was 19/26 patients sei-zure free (73%), 4 patients (15%) had a seizure frequency lower than aseizure per month, and only a patient (4%) had more than one seizure permonth. At five years 15 patients remained for analysis: 11 were seizurefree (73,3%), and 4 (26,7%) had less than a monthly seizure. 7 patientshad postoperative neurological sequelae. In the medical treatment group,12/17 patients were seizure free (70.6%), without significant differences(p = 0.2 and 0.3 respectively).

Conclusion: In patients with non-refractory epilepsy surgical approachof cavernomas did not raised a significative better control of seizures thanmedical treatment, and surgery has potential serious risks. As theseresults are not definitive, it is still necessary a prospective and random-ized study to resolve this uncertainty.

p254ANTIEPILEPTIC DRUG SUSPENSION IN ADULTPATIENTS-ASSESSMENT OF RISK FACTORSS. M. Vujisic, D. B. Milikic, L. B. Radulovic, and S. VodopicClinical Centre of Montenegro, Podgorica, Montenegro

Purpose: To deremine risk factors for the appearence of relapse attacksafter antiepileptic drugs suspension.

Method: A group of patients who had the AE treatment stopped, byadvise and agreement with the doctor, or on the basis of self-initiativewere examined. The study only included patients who had repeated epi-leptic attacks. All the patients had detailed questionnaire filled up, and allof them had neurological examination, EEG and MRI done. Etiology wasclassified into simptomatic, idiopatic and kriptogenic.

Result: A group of 43 patients (aged from 16 to 75 years) were exam-ined due to epileptic attacks after exlusion of the AE therapy. Therewere 20 male and 23 female patients. Most of the patients were 16 to35 years old, i.e 34 (79%). Eighteen patients had idiopatic (42%), thir-teen patients had kriptogenic (30%), and twelve had symptomatic epi-lepsy (28%). Our study has shown that significantly large number ofpatients (p

Conclusion: The most relapses of epileptic attacks occur in the first twoyears after discontinuation of AE therapy. Risk factor for recurrence ispatological EEG. Our study has shown that there was no significant difer-ences in the occurance of relapse regarding etiology.

p255PROVOKED SEIZURES AND FUNCTIONAL OUTCOMEONE YEAR AFTER ACUTE ISCHAEMIC STROKEH. Sent�es-Madrid*, E. Chiquete*, C. Cantffl-Brito*, J. L. Ruiz-Sandoval�, M. Alonso-Vanegas�, and G. Garc�a-Ramos**Instituto Nacional de Ciencias M�dicas y Nutrici�n ‘‘SalvadorZubir�n’’, Mexico City, Mexico; �Hospital Civil de Guadalajara‘‘Fray Antonio Alcalde’’, Guadalajara, Mexico; and �InstitutoNacional de Neurolog�a y Neurocirug�a MVS, Mexico City,Mexico

Purpose: To describe the factors associated with provoked seizures afteracute ischaemic stroke and the impact on functional outcome at one yearof follow up.

Method: This is a descriptive cohort study on 1246 non-epilepticpatients with acute ischaemic stroke included in a multicentre Mexicanregistry, who received long-term follow up after a first-ever or recurrentbrain infarction. Multivariate analyses were performed to evaluate fac-tors associated with provoked seizures and the functional outcome at 12months of follow up.

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Result: The frequency of provoked seizures after acute ischaemicstroke was 8.1% [95% confidence interval (CI): 6.7% to 9.8%]. In abinary logistic regression model, risk factors significantly associatedwith provoked seizures were a scoring of the National Institutes ofHealth Stroke Scale (NIHSSS, US) >10 [odds ratio (OR): 2.21, 95%CI: 1.40–3.47], recurrent ischaemic stroke (OR: 2.17, 95% CI: 1.34–3.53) and age 3) at 12 months of follow up [hazard ratio (HR): 1.37,95% CI: 1.04–1.83], as well as NIHSS >10 (HR: 4.47, 95% CI: 3.53–5.65), age ‡65 years (HR: 1.74, 95% CI: 1.38–2.20), heart failure(HR: 1.61, 95% CI: 1.22–2.13) and atrial fibrillation (HR: 1.35, 95%CI: 1.05–1.74).

Conclusion: The frequency of provoked seizures after acute ischaemicstroke in this cohort was 8%. Age.

p256EPILEPSY REMISSION STAGE STATEMENT BY NON-LINEAR METHODS FOR EEG RESULTS PROCESSINGS. Artsiomenka*, V. Kistsen*, V. Golovko�, and V. Evstigneev**Belarussian Medical Academy of Postgraduate Education,Minsk, Belarus; and �Brest State Technical University, Brest,Belarus

Purpose: Epilepsy remission stage statement and well-founded AEPdose lowering decision are the key points in epilepsy patients’ treatment.We created and used the automatic diagnostic system (ADS) for EEGparoxysmal activity detection to estimate epilepsy remission stage and toearly exacerbation prognosis.

Method: We applied the Neural-Net Method to make the assistant diag-nostic system and examined this system on real EEG data. The largestLyapunov's exponent is used as a criterion for the paroxysmal activitydetection. Therefore a value of the largest Lyapunov's exponent was posi-tive for chaotic behavior of a system and decrease when the epilepsyactivities occur. There were observed 36 patients in epilepsy clinicalremission stage by EEG every 3 month during 1–3 years and then esti-mated results by our ADS. ADS detect parts of EEG which are not cha-otic unlike normal electrical brain activity and gives 2—dimension mapwith colored abnormal parts red.

Result: ADS display paroxysmal activity when usual analysis EEGnot detects anomalies. ADS showed periodically anomaly activityvarious duration in background and particularly photostimulationEEG of all patients with tendency to disappearance of it duringcorrect therapy (p < 0.05). ADS revealed a growth presence of hid-den paroxysmal activity near 6–12 months before exacerbation ofdisease.

Conclusion: Automatic diagnostic system for EEG paroxysmal activitydetection can use to estimate epilepsy remission or exacerbation stagewith prognosis of pre-seizure changes in the EEG signal dynamic to pre-dict a seizure occurrence and to correct the AEP doses.

p257EPILEPSY AS A CHRONIC COMPLICATION IN CERE-BRAL VENOUS THROMBOSIS: A 20—YEAR FOLLOW-UPE. Chiquete*, C. Cantffl-Brito*, M. Merloz-Benitez�, A. Arauz�,H. Sent�es-Madrid*, and M. Alonso-Vanegas�

*Instituto Nacional de Ciencias M�dicas y Nutrici�n ‘‘SalvadorZubir�n’’, Mexico City, Mexico; and �Instituto Nacional deNeurolog�a y Neurocirug�a MVS, Mexico City, Mexico

Purpose: Seizures represent a common clinical presentation of cerebralvenous thrombosis (CVT); however, little is known about the future risk

of epilepsy in patients suffering CVT. Our objective was to analyse therisk factors for epilepsy after CVT, in a long-term follow-up.

Method: This is a cohort study on consecutive non-selected patientswith acute cerebrovascular disease, systematically registered from 1986to 2010 in two referral centres of Mexico City. Here we analysed 340patients who survived the first 6 months after CVT, who were not epilep-tic at baseline and for whom complete long-term information on neuro-logical outcome was available.

Result: Seizures occurred in 183 (54%) patients, in 26% of them as aclinical presentation and 74% at some point during the follow-up. Focalmotor seizures occurred in 6.5%, secondary generalised focal seizures in13.8%, and generalised tonic-clonic seizures in 22.4%. Status epilepticusoccurred in 13 (7%) cases. In all, during a median follow-up of 28 months(range 2 to 288 months), epilepsy was present in 14.7% (27.3% of thosewho presented seizures). In a multivariate analysis adjusted for multipleconfounders, risk factors associated with an increased risk of epilepsyduring follow-up were having seizures as the clinical presentation ofCVT [odds ratio (OR): 4.32, 95% confidence interval (CI): 2.20–8.48],pregnancy and puerperium (OR: 2.03, 95% CI: 1.11–3.71) and thrombo-sis of the longitudinal sinus (OR: 1.86, 95% CI: 1.01–3.41).

Conclusion: Seizures are common at CVT presentation, but the riskincreases during the following days after the thrombotic event. Most sei-zures resolve during the first month, but epilepsy occurred in 15% ofpatients with CVT in the long run.

p258LONG-TERM OUTCOME AFTER COGNITIVE ANDBEHAVIORAL REGRESSION IN NON-LESIONAL EPI-LEPSY WITH CSWSE. Roulet Perez*, T. Deonna*, C. Mayor-Dubois*, M. P. Valenti-Hirsch�, E. Hirsch�, M. Metz-Lutz�, A. De Saint-Martin�, andC. Seegm�ller�

*Centre Hospitalier Universitaire Vaudois, Lausanne,Switzerland; and �University regional hospital centre ofStrasbourg, Strasbourg, France

Purpose: To present the long-term outcome (LTO) of 10 adolescentsand young adults with documented cognitive and behavioral regressionas children due to non-lesional focal, mainly frontal epilepsy with contin-uous spike-waves during slow wave sleep (CSWS).

Method: Past medical and EEG data of all patients were reviewed andneuropsychological tests exploring main cognitive functions wereadministered.

Result: After a mean duration of follow-up of 15.6 years (range 8–23years), none of the 10 patients had recovered fully, but four regained bor-derline to normal intelligence and were almost independent. Patients withprolonged global intellectual regression had the worst outcome, whereasthose with more specific and short-lived deficits recovered best. Themarked behavioral disorders that were so disturbing during the activeperiod (AP) resolved in all but one patient. Executive functions were nei-ther severely nor homogenously affected. Three patients with a frontalsyndrome during the AP disclosed only mild residual executive andsocial cognition deficits. The main cognitive gains occurred shortly afterthe AP, but qualitative improvements continued to occur. LTO correlatedbest with duration of CSWS.

Conclusion: Our findings emphasize that cognitive recovery after cessa-tion of CSWS depends on the severity and duration of the initial regres-sion. None of our patients had major executive and social cognitiondeficits with preserved intelligence as reported in adults with destructivelesions of the frontal lobes during childhood. Early recognition of epi-lepsy with CSWS and rapid introduction of effective therapy are crucialfor a best possible outcome.

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p259TEN-YEAR MORTALITY AMONG PEOPLE WITH EPI-LEPSY (PWE) AT A PRIMARY HEALTH CARE LEVEL:THE CASE OF THE MBAM AREA OF CAMEROONJ. Y. Fonsah*, R. Nchufor�, R. Nditanchou*, Y. F. Fogang*,A. Acho*, R. F. Doh*, F. Dema*, E. N. Tabah�, V. Sini*,A. C. Z. Bissek*, W. F. Muna�, and A. K. Njamnshi�

*Central Hospital Yaounde, Yaounde, Cameroon; �SubDivisional Hospital Ndu, Yaounde, Cameroon; and �NeurologyDepartment, Central Hospital Yaounde, Cameroon; FMBS UYICameroon, Yaounde, Cameroon

Purpose: We aimed at contributing to the improvement of epilepsy carein PWE, understand the natural history of epilepsy, determine the mortal-ity and its principal causes in a group of PWE in the Mbam area of Cam-eroon.

Method: A retrospective analysis of all case files diagnosed with epi-lepsy from 1999 to 2000 in the Mbam area was done. A total of 820 filesof patients followed up in an existing, community-dependent, nurse-con-trolled and neurologist-supervised missionary epilepsy programme werestudied amongst which 192 were analysed.

Result: A mortality rate of 15.1% was obtained with a SMR of 8.9. Moredeaths were recorded amongst females (65.5%) and people of the agegroup 16–25 years (73.2%). Most people lived with the epileptic condi-tion for 11–15 years (42%) before dying with a mean duration of illnessof 11.65 years. Bilomo and Badissa alone recorded more than 50% of alldeaths. The main causes of death were status epilepticus (42.3%), drown-ing (23.1%) and sudden unexplained death (7.7%).

Conclusion: The mortality amongst PWE is high in the Mbam area andinvolves more females and youths. Status epilepticus and drowning arecommon causes of death.

p260LONG-TERM OUTCOME IN ABSENCE EPILEPSIESM. Holtkamp, D. Janz, and A. KirschbaumEpilepsie-Zentrum Berlin-Brandenburg, Berlin, Germany

Purpose: Absence epilepsies are classified regarding age at onset intochildhood (£10th year of life) and juvenile (>10th year) and regardingclinical course with high- and low-frequency seizures into pyknolepticand non-pyknoleptic forms. Prognostic data may help to clarify if theserepresent different entities or constitute parts of a clinical continuum thatis based on the same neurobiological syndrome.

Method: 147 patients with absence epilepsies and a follow-up of ‡20 awere included. Diagnostic allocations were made on the basis of clinicaland EEG data derived from patient charts. Terminal remission wasdefined as seizure freedom in the last 5 years.

Result: After a mean follow-up of 45 € 15 years, 75 patients (51%) wereseizure free, 22 of those were tapered off antiepileptic drugs (AED). Fol-lowing multivariate analysis, history of generalised tonic-clonic seizures(GTCS) (OR 7,680; CI95% 1.546–38.159; p = 0.013) and age at investi-gation (OR 0.958; CI95% 0.935–0.982; p = 0.001) were independent pre-dictors for lacking remission.

Conclusion: More than half of the patients with absence epilepsies wereseizure free for the last 5 years, one third of those did not take AEDs.Thus, nearly one in six patients was cured from absence epilepsy almosthalf a century after onset. Lack of remission was a function of patients’age and occurrence of GTCS. Neither age at epilepsy onset nor the clini-cal course with pyknoleptic vs. non-pyknoleptic absences was associatedwith long-term outcome. This important clinical feature biologicallyrather argues for a continuum than for a dichotomisation of absence epi-lepsies into a childhood and juvenile form.

p261PROGNOSTIC FACTORS FOR TIME TO TREATMENTFAILURE AND TIME TO 12 MONTH REMISSION FORPATIENTS WITH GENERALISED EPILEPSY: POSTHOC AND SUBGROUP ANALYSES OF SANADL. J. Bonnett*, C. Tudur Smith*, D. Smith�, P. Williamson*,D. Chadwick�, and A. Marson�

*University of Liverpool, Liverpool, UK; and �Walton Centrefor Neurology and Neurosurgery NHS Foundation Trust,Liverpool, UK

Purpose: Epilepsy is a heterogeneous condition with outcomes rangingfrom immediate remission on a first antiepileptic drug through to fre-quent unremitting seizures with multiple treatment failures. There arecurrently few published prognostic models for epilepsy that allowinformed decision making based on predicting outcomes overall and onspecific treatments.

Method: A list of potential prognostic factors was established and uni-variate and multivariable analyses using Cox regression models wereundertaken. Variables were centred to diminish multicollinearity andcontinuous variables were investigated by log or fractional polynomialtransformations. Parsimonious multivariable models were produced withvariable reduction by Akaike's Information Criterion.

Result: Multivariable models identified a number of significant factors.For time to treatment failure, treatment history (recent seizures followingprevious remission vs treatment naive: HR 2.01 95% CI (1.18 to 3.41)),EEG results (no results vs normal results: HR 2.45 95% CI (1.46 to4.09)), total number of seizures before randomisation (e.g. 4–8 vs £2: HR1.49 95% CI (1.19 to 1.85)) and treatment (topiramate vs valproate: HR1.62 95% CI (1.22 to 2.16)) were significant factors. For time to 12 monthremission significant factors were relatives with epilepsy (present vsabsent: HR 0.75 95% CI (0.59 to 0.95)), neurological insult (present vsabsent: HR 0.70 95% CI (0.52 to 0.93)) and total number of seizuresbefore randomisation (e.g. 4–8 vs £2: HR 0.41 95% CI (0.33 to 0.51)).

Conclusion: Subject to external validation, this prognostic modelshould aid individual patient risk stratification and the design and analy-sis of future epilepsy trials.

p262MORTALITY AND SUDEP IN EPILEPSY PATIENTSTREATED WITH VAGUS NERVE STIMULATIONC. A. Granbichler*, L. Nashef�, C. E. Polkey�, and R. Selway�

*Christian Doppler Klinik, Salzburg, Austria�King's CollegeHospital, London, UK; and �King‘s College London, London,UK

Purpose: Data on mortality with Vagus Nerve Stimulation (VNS) forepilepsy are limited. In one study, standardized mortality ratio (SMR)was 5.3 [95% confidence interval (CI) 3.0–8.7] with a rate of definite/probable SUDEP of 4.5/1,000 person-years (py) (Epilepsia 1998Feb;39(2):206–12). Mortality rates were lower (SMR = 3.6) withextended follow-up. Stratified by duration of use, SUDEP rate was 5.5/1,000 over the first 2 years, and 1.7 per 1,000 thereafter (Epilepsia 2000May;41(5):549–53). To establish mortality rates, identify epilepsy-related deaths and calculate SUDEP rates in patients treated with VNSfor epilepsy.

Method: All UK-based patients undergoing VNS at King's College Hos-pital, London, between 1st January, 1995 and 31st December, 2010 wereincluded. Deaths were ascertained from the national death register. Infor-mation on cause and circumstances of death were obtained as appropriate.Deaths were designated as epilepsy or not epilepsy related and SUDEPcases classified using the unified definition (Epilepsia, 53(2):227–233,2012). SMRs were calculated on an intention to treat basis.

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Result: There were 445 patients (2734 person-years [py], median fol-low-up 6.1 years) and 29 deaths (SMR 7.6 [95% Confidence Intervals(CI), 5.3–10.9]. On preliminary classification, 13 deaths were epilepsy-related, including 7 SUDEP (5 definite, 2 probable), and 3 are unclassi-fied (further information awaited). Overall SUDEP rate/1000 py was 2.6,2.4 during the first two years, and 2.7 thereafter.

Conclusion: SMR in our cohort is higher but not significantly so. Preli-minary results do not confirm a decrease in SUDEP rate beyond the firsttwo years in this cohort.


p263IS TERMINAL REMISSION WITHOUT THERAPY POS-SIBLE IN PATIENTS WITH JUVENILE MYOCLONICEPILEPSY?N. J. Jovic, and A. KosacClinic of Neurology and Psychiatry for Children and Youth,Belgrade, Serbia

Purpose: It has been generally accepted that juvenile myoclonic epi-lepsy (JME) is lifelong and that it is unwise to discontinue treatment onceseizure control has been established. The evolution of JME in patientswith long-term seizure freedom and antiepileptic drugs (AEDs) discon-tinuation was assessed.

Method: We retrospectively analyzed clinical course of 87 JME patients(38 male, 49 female) aged from 17.5 to 43.5 years (mean 27.6), withmean seizure onset of 14.6 years (range 8.3–20.8).

Result: Complete seizure control was achieved in 67 (77.0%) patientsmainly with valproate (55 patients). Pseudo-resistant seizures occurred in9.2%, while JME was refractory in 13.8% patients. Therapy was discon-tinued in 34 (39.1%) patients (in 13 by their own choice after 5.3 + 2.4and in 21 following advice of a physician after 8.5 + 5.2 years of seizurefreedom). In 18 subjects seizures relapsed after mean 1.1 year (range 7days to 4 years) and AED was restarted. In two patients the AED wasreintroduced because of EEG aggravation. Seizure and drug freedom ofmean 5.1 years (range 3.5–12 years) was noted in 11.5% patients. Nonin-trusive myoclonic seizures recurred for 2.4–4 years as their only seizuretype in 4 subjects, but without restarted medication.

Conclusion: Terminal remission without AEDs is possible in JMEpatients. Non-compliant individuals have lower chance to achieve it. Allseizure types in JME resolved in 11.5% and for 4.6%, only myoclonuspersisted. Therefore, 16.1% of adolescents and young adults with JMEhave troublesome seizures vanished and AED treatment was no neededfor years.

p264CARDIAC ARRHYTHMIAS MAY BE UNDERESTI-MATED IN PEOPLE WITH CHRONIC EPILEPSYR. J. Lamberts*, J. Novy�, H. L. Tan�, R. D. Thijs*, andJ. W. Sander�

*SEIN-Epilepsy Institute in the Netherlands Foundation,Heemstede, The Netherlands; �UCL Institute of Neurology,London, UK; and �University of Amsterdam, Amsterdam, TheNetherlands

Purpose: People with chronic epilepsy are known to be at risk of prema-ture mortality mainly due to sudden unexpected death in epilepsy (SU-

DEP). The exact mechanisms of SUDEP are not known and severalhypotheses (such as cardiac, respiratory, autonomic causes) have beenadvanced. People with epilepsy also seem to have more concomitantmedical conditions than the general population; some cardiac co-morbid-ities (such as Brugada syndrome) may play a role. We aim to explore theprevalence of significant cardiac arrhythmias in these people.

Method: To date, we have collected consecutive standard (12 leads)ECGs of 100 people assessed for chronic epilepsy in 2010 in a tertiaryreferral centre. ECGs were reviewed by an experienced cardiologist(HLT), looking for subtle abnormalities. All concomitant medications aswell as cardiovascular risk factors and history were taken into account.

Result: In those 100 people, amongst other abnormalities detected, theECGs of two were highly suggestive of Brugada syndrome. Neither waspreviously known to have this condition and this had not been detectedby automated analysis of the ECGs or by previous review.

Conclusion: The prevalence of Brugada syndrome may be higher inpeople with chronic epilepsy than in the general population where it wasfound in several studies to be less than 0.1%. This condition is known tobe lethal and could be responsible for some cases of SUDEP. Channelop-athies affecting both heart and brain could explain its increased occur-rence in epilepsy. We aim to increase the size of our sample to confirmthese findings.

p265HAS TREATMENT OF EPILEPSY IMPROVED IN THEPAST 10 YEARS? THE IMPACT OF EPILEPSY TREAT-MENT IN THE PAST 10 YEARS; A COMMUNITY-BASED COMPARISON STUDYM. Wassenaar*, F. S. S. Leijten�, P. Van Der Linden�, S. G. Uijl§,A. C. G. Egberts–, and J. A. Carpay�

*UMC Utrecht, Utrecht, The Netherlands; �Rudolf MagnusInstitute of Neuroscience, UMC Utrecht, Utrecht, TheNetherlands; �Tergooi ziekenhuizen Blaricum, Blaricum, TheNetherlands; §Julius Center for Health Sciences and PrimaryCare, UMC Utrecht, Utrecht, The Netherlands; and –UtrechtInstitute for Pharmaceutical Sciences, University Utrecht,Utrecht, The Netherlands

Purpose: New-generation AEDs have increased the number of treat-ment options for epilepsy and are promoted because of better safetyprofiles. It is unknown if this has resulted in better patient outcomesin daily practice. We describe 10—year changes in quality of life(QoL), seizure control and drug-related adverse effects (DRAEs) in acommunity-based sample of epilepsy patients and assesses potentialpredictors of QoL.

Method: From two cross-sectional community-based studies performedin 2000 and 2010 in a Dutch suburban region, responses to standardizedquestionnaires on treatment outcomes were compared. Epilepsy patientswere identified using pharmacy records, 344 and 247 patients wereincluded respectively. Additionally, factors, among which seizure controland DRAEs, predicting QoL were assessed by multivariate linear regres-sion.

Result: New-generation AEDs prescription in 2010 increased to 44.5%from only 10.5% in 2000. Treatment outcomes did not differ betweennew and old-generation AEDs. In 2010 compared to 2000, QOLIE-31scores did not differ (72.48 vs 72.54), neither did the proportion ofpatients reporting well-controlled seizures (55.1% vs 50,5%). However,seizure acceptability increased (54.3% vs 40.3%) and AEs were signifi-cantly more reported (82.0% vs 58.9%). Seizure control, DRAEs and sei-zure acceptability jointly predicted QoL score (R2 = 51%).

Conclusion: The introduction of new AEDs has not improved QoL inthe past decade. Whereas seizure acceptability increased, seizure control

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remained similar and DRAEs were reported more frequently. Since allthese factors contributed to QoL, reduction of DRAEs should be priori-tized to improve QoL in epilepsy patients.

p266CARBAMAZEPINE AND OXCARBAZEPINE TRIG-GERED EPILEPTIC NEGATIVE MYOCLONUS AGGRA-VATION IN CHILDHOODK. Y. Mukhin, and M. B. MironovSt. Luka's Institute of Child Neurology and Epilepsy, Moscow,Russia, Moscow, Russian Federation

Purpose: Investigation of patients with ENM induced by Carbamaze-pine (CBZ) and Oxcarbazepine(OXC).

Method: The 12 patients with ENM who have been taking CBZ or OXCin the course of treatment. In 10 of 12 cases, ENM was induced by thesedrugs.

Result: In 10 cases (83,3%) ENM aggravation was noted.As our results show, there are several CBZ/OXC triggered ENM

aggravation risk factors: males prevail over females at a ratio of 4 to 1;age of onset of epilepsy: from 1 year to 13 years of age with a peakbetween the ages of 3 and 8 years; forms of epilepsy: FEBL-BEDC – 5cases, epileptic encephalopathies associated with BEDC – 3 cases, symp-tomatic focal epilepsy with SBS on EEG – 1 case, progressive myoclonusepilepsy (PME) – 1 case. Types of seizures preceding the ENM events:hemiconvulsive – 7 patients; SGTCS – 5 cases; tonic seizures – 2; occipi-tal focal seizures – 2; GTCS – 1; myoclonic seizures – 1 case.

p267NEONATAL PARAMETERS AS PROGNOSTIC FAC-TORS FOR EPILEPSY OR CEREBRAL PALSY ININFANTS WITH HYPOXIC-ISCHEMIC ENCEPHALOP-ATHYN. M. Cerovac, and N. J. JovicDepartment for Neurology and Psychiatry for Children andYouth, Medical School, Belgrade, Belgrade, Serbia

Purpose: The survivours with hypoxic-ischemic encephalopathy (HIE)were studied to evaluate the prognostic value of neonatal parameters asrisk factors for cerebral palsy (CP) and epilepsy.

Method: A group of 45 infants with HIE were retrospectively assesed atbirth and at seven year of age. Perinatal conditions, neonatal parameters,neurological status, 5-minute Apgar score and early electroencephalo-gram (EEG) were analysed.

Result: The neurological outcome at the age of seven years wasnormal in 9 infants (20%) and abnormal in 36 (80%). Both epilepsyand CP developed in 9 infants (20%), only motor delay in 30%,only epilepsy in 4% or only CP in 26%. Seizures were classified asinfantile spasms (4 infants), complex focal (3) and generalized tonic-clonic (2). Obstretic complications were:pre-eclampsia (13%), abrup-tio placentae (11,1%), chorioamnionitis (20%), breech delivery(11%), cord prolapse (11%), meconium (20%) and caesarean section(33%). The mean gestational age of the group was 36 weeks, meanbirth weight 2,4 kg and the mean Apgar score 6,9. The neonatalneurological status was normal in 31% of infants and abnormal in69%. Early EEG was normal in 22% of infants and abnormal in78% (abnormalities in EEG background rhythm and/or pathologicpatterns). The results of our study confirm that neonatal neurologicalstatus (v2 = 11,431; p = 0,0007) and early EEG (v2 = 8,481; p =0,0036) were a good predictive factors in terms of neurologicalsequelae, while other neonatal parameters did not show such a goodcorrelation.

Conclusion: Neurological status and EEG are crucial parameters whichcould identify infants at risk of CP and epilepsy.

p268RELIABILITY AND VALIDITY OF A SPANISH VER-SION OF THE IMPACT OF PEDIATRIC EPILEPSYSCALE IN A CUBAN POPULATIONN. Gar�falo G�mez, O. Fern�ndez Concepci�n, andA. M. G�mez Garc�aCuban Institute of Neurology and Neurosurgery, Havana, Cuba

Purpose: The Impact of Pediatric Epilepsy Scale (IPES) is a brief, accu-rate, and acceptable measurement scale of the impact of pediatric epi-lepsy on the Health Related Quality of Life (HRQOL) of both the childand family as perceived by the child's parent(s) and has been previouslyvalidated in Canadian and Chinese children with epilepsy. The aim of thisstudy was to validate a Spanish language version the IPES in Cuban chil-dren with epilepsy.

Method: The IPES was translated and adapted to Cuban culture andadministered to 76 parents of children with epilepsy.

Result: The principal component analysis indicated that two factorsaccounted for 72% of the variance of IPES scale (family relationshipsand health and social well-being). The IPES also was able to detect differ-ences in health-related quality of life (HRQOL) between subjects accord-ing to epilepsy severity. Internal consistency coefficients were 0.962 andthe test-retest reliability was 0.979.

Conclusion: The Cuban Spanish version of IPES has good validity andreliability, and can be used to measure a child's epilepsy specific HRQOLin Cuba and probably in other Spanish speaking communities.

p269MANAGEMENT OF ACUTE SYMPTOMATIC SEI-ZURES – OUTLINE OF CURRENT PRACTICER. Powell, and I. M. SawhneyMorriston Hospital, Swansea, UK

Purpose: Acute symptomatic seizures (ASS) are seizures occurring atthe time or in close temporal association with a documented systemic orbrain insult. The major issues involved in their management are the diag-nosis and treatment of the underlying cause, whether seizures should betreated or not, and the choice and duration of anti-epileptic drug (AED)treatment. These decisions are not straightforward and currently no clearguidelines exist to guide management in this area.

Method: We reviewed the literature on risks of ASS and epilepsy fol-lowing a number of common conditions.

Result: We outline our current practice in this area which is based on theevidence available on risks of seizure recurrence, and on our own experi-ence.

Conclusion: Most ASS only need short term therapy (up to 3 months) ifthere is complete recovery from the acute insult. Patients with residualstructural brain abnormalities with focal neurological deficit and/or MRIchanges need long term prophylactic treatment. We make some sugges-tions for duration of treatment for ASS associated with a number of com-mon conditions, including; – subarachnoid and intracerebralhaemorrhage – 1 year – ischaemic stroke and venous sinus thrombosis –1 year – mild to moderate head injury – acute seizure control only –severe head injury – 2 years -metabolic and toxic disorders (includingalcohol withdrawal) – correction of underlying cause only – meningoen-cephalitis with complete recovery, normal MRI – 3 months, residualfocal deficit and/or MRI changes – 2 years

- cerebral abscess, tuberculoma and parasitic granuloma –– 2 years

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p270REFRACTORY SEIZURES AND QOL: CAN A PATIENTBE WORSE OFF ON AEDS? 3 CASE STUDIESS. White, and L. D. MewasinghImperial College Healthcare NHS Trust, London, UK

Purpose: 3 clinical cases are discussed whereby the common theme isthat of refractory seizures, of different aetiologies, but nontheless raisingthe question of whether polypharmacy is justified when clinically theredo not seem to be any significant clinical response to various AEDS indifferent combinations over time. In each case the seizures have beenproven to be concordant with numerous electrographic recordings over aperiod of time.

Method: Aetiologies: Case 1: a 2 year old with severe neonatal herpesencephalitis with significant sequelae (4—limb cerebral palsy, corticalblindness, numerous seizure types as well as non-epileptic movementdisorder) and feeding problems Case 2: a young boy with Wolf Hirshornand refractory epilepsy disorder including episodes of nonconvulsive sta-tus epilepticus, resistant to various AEDs as well as no clincal response toketogenic diet Case 3: a teenager with herpes simplex encephalitisacquired in her primary school years with frontal disinhibition, moderatelearning difficulties and refractory seizure disorder.

Result: In the first two cases parents were clear that they did not wishfor further medications, perceived as of minimal benefit and resulting indecreased alertness. In the third case, parents and professionals differedin what was perceived as optimal QOL for the young person, with the for-mer keen to pursue various therapeutic avenues with little clinical tangi-ble improvement.

Conclusion: The issues of QOL, polypharmacy, perceived side effectsof treatment versus benefits are raised and discussed. This can at timeslead to the dilemma of whether to treat and how aggressively to treat sei-zures in this context.

p271A STUDY OF STANDARDISED MORTALITY RATE INPEOPLE WITH INTELLECTUAL DISABILITY WHODIED OF SUDDEN UNEXPECTED DEATH IN EPILEPSY(SUDEP)R. KianiLeicestershire Partnership NHS Trust, Leicester, UK

Purpose: To calculate the mortality rate of Sudden Unexpected Deathdue to Epilepsy in people with intellectual disability and evaluate thequality of epilepsy management they received from an adult intellectualdisability service.

Method: All adults, with an intellectual disability, who had diedbecause of epilepsy between 1993 and 2010 were identified usingthe Leicestershire Intellectual Disability Register database. Deathcertificates and post-mortem reports were used to ascertain the causeof death. Case notes review was then carried out to collect furtherinformation.

Result: A total of 898 patients with intellectual disability had died overthe 18— year study period. The all cause specific Standardised MortalityRatios were 2.4 (95% CI=2.1–2.6) and 3.0 (95% CI=2.6–3.3) for malesand females respectively. 244 of deaths occurred in people with a diagno-sis of epilepsy rendering a Standardised Mortality Ratio of 3.2 (95%CI=2.6–3.8) for men and 5.6 (95% CI=4.6–6.7) for women. SUDEPStandardised Mortality Ratio was 39.6 for men (95% CI=23.1–63.4) and52.0 for women (95% CI=23.7— 98.8). The majority of these serviceusers were male, of Caucasian ethnicity, and with a significant degree ofintellectual disability (IQ<50). A significant number of patients had co-morbid autism, physical and mental health problems, poorly controlledepilepsy and took more than one antiepileptic agent.

Conclusion: Clinical record keeping was generally poor particularlyregarding the circumstances surrounding deaths and raising awareness ofSUDEP among patients/carers. There was also an absence of post-mor-tem reports and no record of support provision for families to cope withtheir bereavement in the majority of cases.

p272EPILEPSY AND PSYCHIATRIC DISORDERS IN A‘‘LEARNING DISABILITY’’ PATIENT'S SERIESV. C. Monetti, E. Fallica, V. Govoni, and E. CesnikAzienda Ospedaliero Universitaria di Ferrara, Ferrara, Italy

Purpose: Epilepsy is most frequent in Learning Disability (LD) patients.The frequency ranges from 6% (moderate LD) to 50% (severe/profoundLD). The object of our study is to analyse a LD outpatients series fol-lowed up in the Adult Epilepsy Center of Ferrara Hospital to evaluatetheir long-term prognosi and eventual conditioning clinic and psycoso-cial factors involved.

Method: In the Ferrara Hospital Adult Epilepsy Center database LDpatients, in follow-up from more than 10 years with the last examinationin the years 2010–2011, were identified. Their data were crossed with thedata of the same patients who were previously followed-up in the Paedi-atric Epilepsy Center to obtain a long-term observation.

Result: 86 patients were identified (35 F, 51 M, mean age 41 years).76% of them had a symptomatic Epilepsy (mainly pre- post-natal injuryanda cerebral malformations) whereas 9% had a chromosomal-geneticdisorder. In the 43% of the cases the seizures frequency was high (>2/month) from the onset with no significant improvement over time. 48%of patients had a drug-resistant epilepsy. Psychiatric disorders were pres-ent in 48% of patients and almost all of them were institutionalised.

Conclusion: Our findings support limited evidence from the literaturethat the LD severity does not affect the prognosis of epilepsy as the highfrequency of seizures at onset. Psychiatric comorbidity is prognosticallyunfavourable factor for an institutionalization.


p273COMPLEX PARTIAL STATUS EPILEPTICUS DUE TOHIPPOCAMPAL SCLEROSIS AS THE INITIAL MANI-FESTATION OF PEDIATRIC-ONSET MIXED CONNEC-TIVE TISSUE DISEASED. Athanasopoulos, D. Kitsos, E. Vasileiadis, andS. GiannakodimosGeneral State Hospital of Athens, Athens, Greece

Purpose: Mixed connective tissue disease (MCTD) diagnosis is basedon specific clinico-laboratory criteria with rare onset in childhood. Wepresent a 16—year-old adolescent with complex partial status epilepticusas the initial manifestation of pediatric-onset MCTD.

Method: The patient was admitted following a prolonged (>12 hours)state of altered consciousness and disorientation, which ended up withtwo secondary generalized tonic-clonic seizures. Family/personal historyfor epilepsy was negative. No perinatal problems, febrile seizures or headtrauma were reported.

Result: Interictal EEG showed spikes/sharp waves over the left anterior-temporal regions and a 4—sec duration paroxysmal generalized 3 Hz

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spike-wake discharge. MRI-brain was compatible with left-sided hippo-campal sclerosis (HS) (ipsilateral hippocampal and fornix atrophy, lateralventricle dilatation and high T2/FLAIR signal of the hippocampus). Oninterviewing he reported muscle weakness and joint aches on the lowerextremities. Physical examination revealed swollen fingers. Laboratorytests showed elevated CPK, positive anti-snRNP70 and ANA. Based onthe Kasukawa criteria a definite MCTD diagnosis was made.

Conclusion: Genetic or environmental factors may lead to hippocampaltissue injury and HS, evolving to mesial temporal lobe epilepsy (MTLE).Although MCTD-associated HS has not been reported, Central NervousSystem (CNS) may be affected via vascular or inflammatory mecha-nisms, leading to early neurological manifestations. Correlation ofMCTD with anti-SSA/ro seropositivity with neurological manifestationsis already established. We hypothesize on probable similarities with Sys-temic Lupus Erythematosus regarding vasculitis-induced CNS involve-ment and HS development. Our case indicates that MTLE may be aconsequence of MCTD. Should HS is revealed an underlying vasculiticmechanism could be hypothesized.

p274STATUS EPILEPTICUS AND MULTIPLE SCLEROSISCASE OVERVIEWD. Sahovic, and Z. SavicClinical Center University of Sarajevo, Sarajevo, Bosnia andHerzegovina

Purpose: To present the case of a patient with a several years history ofmultiple slerosis with sudden status epilepticus.

Method: The patient is 41 years old, with a 12-years clinical history ofmultiple sclerosis. The patient was treated and monitored well, and didnot show any symptoms of any form of epileptic seizure. She suddenlypresented a partial motor seizure with secondary generalization whichevolved to the epileptic status of tonic and clonic spasms. Upon admis-sion to the Intensive Care Unit, electroencephalographic investigationsrevealed EEG changes with specific epileptiform discharges (3.5 Hz S-Wcomplexes) over the frontal lobe. EEG control showed normalization fol-lowing medical therapy.

Result: Since the previous treatment of the patient for the basis diseasenever revealed a possibility of developing of any form of epileptic sei-zure, a sudden and serious nature of her current status indicates the needfor continuous caution and regular EEG monitoring of such patients.

Conclusion: Multiple sclerosis patients may at any stage of the diseasebe at risk of a symptomatic form of epilepsy as an isolated seizure or apermanent form of epilepsy.

p275GENERALISED SEIZURES AS FIRST CLINICAL MANI-FESTATION OF DIFFERENT FOCAL CEREBROVAS-CULAR IMPAIREMENTD. I. CuciureanuUniversity of medicine ‘‘Gr T Popa’’, IASI, Romania

Purpose:

Background: To characterize and discuss an unusual etiology for gener-alized seizures in a small series of cases.

Methods: We reviewed the clinical features and laboratory data of1120 patients hospitalized for epilepsy in our neurological serviceduring past 5 years, and we emphasize 2 cases with generalized sei-zures as first clinical manifestation of different focal cerebrovascularimpairment.

Results: Patients were investigated by clinical examination, neuropsy-chological test, brain computed tomography, vascular related bloodtests, EEG studies, angio MRI in selected cases. We find 72% general-ized seizures and 28% focal seizures. Among generalized seizures 74%had only seizures and headache with no neurological objective signs.Regarding the etiology of these cases we find: tumors 6.3%, silent cor-tical ischemic lesions 6%, unexplained sequel lesion (porencefalia)3.6%, no imagistic lesion 71% and focal vascular lesion in 13% (duralsinus thrombosis – 49%, cerebral cavernous malformation – 30%, cere-bral vascular aneurysm 21%). We describe the 2 cases of femalepatients with generalized seizure as first neurological manifestationdue to a frontal cavernoma and to a longitudinal sinus thrombosis withno objectives neurological signs. EEG revealed synchronous paroxysmof generalized polyspikes and the MRI angiogram detected 2 type offocal vascular impairment.

Conclusion: Despite the focal vascular lesions, the existence of clinicalfirst manifestation as primary generalized seizures must underlie a com-plementary, still unknown, pathological mechanism.

p276ANTECEDENTS OF DRUG RESISTANT TEMPORALLOBE EPILEPSY WITH AND WITHOUT HIPPOCAM-PAL SCLEROSIS: A COMPARATIVE STUDYG. Shukla, and V. GoyalAll India Institute of Medical Sciences, New Delhi, India

Purpose: To examine the role of initial precipitating events (IPE) inpatients with drug resistant temporal lobe epilepsy (TLE) with and with-out hippocampal sclerosis.

Method: Retrospective chart review of 171 patients diagnosed to havetemporal lobe epilepsy based on clinical history, ictal video-EEG andMRI. Patients were categorized into two groups; [Group 1] with historyof drug resistant TLE and MRI evidence of HS and Group 2 without HS,with or without other structural abnormality. Both groups were comparedfor age, gender, age at onset and duration of epilepsy, time to intractabil-ity, age at first febrile seizure (FS), frequency of FS, history of IPEs[including history of perinatal asphyxia, meningitis, encephalitis, headtrauma], age at spontaneous remission. Statistical analysis was carriedout using Mann Whitney test for continuous variables and Fisher's exacttest for discrete variables (p

Result: Seventy-two patients [24 female] with mean age of 26 + 11years [range 8 to 55] fell in Group 1 with 99 patients [24 female]with mean age 21.6 + 10 years [range 3 to 60] in Group 2. Age atonset of epilepsy was significantly lower in Group 2 while a historyof perinatal asphyxia and prolonged FS were more frequent inGroup 2 (p

Conclusion: A younger of age of presentation, (IPE) history of pro-longed FS and a history of perinatal asphyxia were significant in patientswith drug resistant TLE without hippocampal sclerosis. These findingsraise the possibility of a distinct subgroup of patients with TLE who aretreatment resistant with an early onset of epilepsy.

p277TREATMENT EFFICACY OF SYMPTOMATIC EPI-LEPSY IN POST STROKE PATIENTSH. D. Hambardzumyan, and H. M. ManvelyanYerevan State Medical University, Yerevan, Armenia

Purpose: Post stroke patients often develop not only physical or motorimpairment, but also cognitive decline and in some cases, mainly associ-ated with cystic transformation of the brain tissue, they develop epilepticseizures also.

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The aim of this study is effective treatment of post stroke patients withsymptomatic epileptic seizures.

Method: 27 patients (12 women and 15 men) of the age of 62 € 6 years,who met selection criteria: arterial hypertension, ischemic stroke, intra-cerebral cyst verification by MRI or CT scans and symptomatic epilepsy,were selected for this study. All of them had at list one seizure and posi-tive EEG.

Result: Cognitive impairment was assessed by modified Wechsler scale(71 point maximum), was in range of 33 € 8. 13 out of 27 patients tookCarbamazepin 600 mg daily, in two months of observation period theywere free of seizures, but the Wechsler score decreased till 28 € 6. 14patients took Gabapentine 900 mg daily, in two months period they werefree of seizures also, and Wechsler score was 32 € 6.

Conclusion: Both medications in mean therapeutic doses are effectivein prophylaxis of seizures in post stroke patients, but Carbamazepincauses decline in cognitive function in two months, whether patients onGabapentine kept cognition level constant. The choice of medication intreatment of post stroke epilepsy must be done in accordance of theirinfluence on cognitive functions also.

p278COMPARISON OF SOMATIC COMORBIDITY INCI-DENCE IN YOUNG ADULTS WITH IDIOPATHIC ANDSYMPTOMATIC EPILEPSYL. B. Mar’Yenko, and K. M. Mar’YenkoLviv, Ukraine

Purpose: To compare the frequency and variety of somatic comorbidityin young adult patients with idiopathic (IE) and symptomatic epilepsy(SE) and duration of the disease more than 5 years.

Method: We followed up (in the course of 5–10 years) two groups ofpatients aged 18–40 years: 38 persons with IE (12 males, 26 females)with persistence of seizures from childhood or adolescence and meanduration of the disease 13.7 years and 94 persons (47 males, 47 females)with SE and mean duration of the disease 9.7 years. Complete clinicalneurological and somatic examination with adequate para-clinical inves-tigations were used to confirm the presence of somatic pathology.

Result: In patients with IE somatic diseases were found in 50.0% ofmales and 42.3% of females, in SE patients – in 53.2% and 72.3% accord-ingly. The most common somatic comorbidities in SE group werechronic ENT diseases (20.2%), GIT pathology (20.2%), ANS disorders(7.4%), urological (6.4%) and skin and joints diseases (3.2%). In patientswith IE the most frequent pathology was endocrine one (especially men-strual disorders in females) – 15.8%, ENT (13.2%) and GIT diseases(7.9%) as well as migraine (7.9%). Females with IE have higher frequen-cies of menstrual disturbances and polycystic ovaries than women withSE (t= )1.99, p £ 0.05), which may be explained by usage of valproates.Women with SE have higher incidence of other somatic comorbidities(t=)2.61, p £ 005).

Conclusion: A high percentage of patients with epilepsy have somaticcomorbidity, which should be taken into account while selecting anappropriate AED treatment.

p279FIBRINOLYSIS AND SYMPTOMATIC EPILEPTIC SEI-ZURES: PREVENTION OR INDUCTIONM. J. Aguilar Amat PriorHospital Universitario La Paz, Madrid, Spain

Purpose: Evaluating if intravenous (IV) treatment with rt-PA influencesin appearance of symptomatic epileptic seizures after acute cerebralinfarct.

Method: Observational case-control study (1:3) of patients with a non-lacunar acute cerebral infarct, seen in a Stroke Unit (2008–2009). Cases:patients treated with IV rt-PA. Controls: patients not treated with IV rt-PA, paired with cases according to severity (NIHSS), and cerebral arteryinvolved. Patients with previous epilepsy, brainstem infarct, or neuroin-terventionist treatment, were excluded. Variables: basal data, strokeseverity (NIHSS), etiology, involvement of cerebral cortex and appear-ance of early (<7 days) or late (>7 days) symptomatic seizures.

Result: 147 patients, 49 cases. Mean age was less in cases than in con-trols (66.51 Vs 72.78; p = 0.007). Proportion of males was similar (57.1%Vs 44.9%; p = 0.162). Cases had more frequently uncommon etiologyinfarcts (14.3% Vs 4.1%; p = 0.042). There were no differences in vascu-lar risk factors, previous treatment, nor cerebral cortex involvement.Early and late seizures were similar between cases and controls (6.1% Vs7.1%, and 10.2% Vs 7.1%, respectively; p=NS). Hemorrhagic transfor-mation was the only independient predictor factor in early (OR 5.69; CI90% 1.44–22.45) and late (OR 3.71; CI 95% 1–13.76) seizures, adjustedby age, sex, NIHSS, cerebral cortex involvement and IV rt-PA.

Conclusion: Treatment with IV rt-PA doesn't influence in the develop-ment of symptomatic seizures after an acute cerebral infarct. Hemor-rhagic transformation is a predictor factor of such seizures.

p280EPILEPSY ASSOCIATED WITH CEREBROTENDINOUSXANTHOMATOSIS SUCCESFULLY TREATED BYCHENODEOXYCHOLIC ACIDP. Vrielynck*, A. Marchese�, D. Roland�, F. Li�nard�,S. Andries�, S. Ghariani�, and K. Van Rijckevorsel�

*Centre Neurologique William Lennox, Ottignies, Belgium;�Centre Neurologique William Lennox, Reference Center forRefractory Epilepsy, Universit� Catholique de Louvain,Ottignies, Belgium; and �Institut de Pathologie et de G�n�tique,Gosselies, Belgium

Purpose: Cerebrotendinous xanthomatosis (CTX) is a rare autosomicrecessive metabolic disease causing cholesterol and cholestanol accumu-lation in multiple tissues. Clinical phenotype is variable, includes pro-gressive neuropsychiatric deterioration. Epilepsy could occur in up to50% of patients. Chenodeoxycholic acid (CDCA) may lead to clinicalimprovement. Here we describe electro-clinical evolution of epilepsyassociated with CTX in a young male patient .

Method: The patient was seen for the first time at our clinic at 16 year-old. He presented with mental retardation, behavioral disturbance, ataxia,peripheral neuropathy, bilateral cataract and epilepsy. MRI showed mul-tifocal lesions of white matter. Cholestanol elevation in blood andCYP27A2 homozygous mutation (c. 1263 + 1 G>A) were found, estab-lishing diagnosis of CTX. 24 hour EEG was performed before and afterCDCA introduction.

Result: Between 6 and 14 months, the patient had frequent bilateralmyoclonia leading initially to diagnosis of benign myoclonic epilepsy,with good response to valproate. At 12 years, different seizures typesoccurred: myoclonia, generalized tonic-clonic and drop attacks. EEGshowed diffuse slowing of background activity and diffuse polyspikesduring wake and sleep, sometimes associated with myoclonia. Seizuresbecame resistant to lamotrigine, levetiracetam and topiramate. CDCAwas introduced at 17 years. A few months later, neuropsychiatric statusimproved, myoclonia and tonic-clonic seizures disappeared and fre-quency of drop attacks decreased to less than one episode per month.Three years later, improvement persists. Epileptiform discharges havedisappeared on wake and sleep EEG .

Conclusion: CTX is a rare cause of generalized symptomatic epilepsy.Early diagnosis and treatment may improve neurological status andepilepsy.

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p281EPILEPSY IN PATIENTS WITH TUBEROUS SCLERO-SIS COMPLEXS. T. Ristic*, D. T. Ristic�, I. Marinkovic�, and G. Djordjevic**Clinical Centre of Nis, Nis, Serbia; �Institutae of PulmonaryDisaeses, Nis, Serbia; and �Medical Faculty of Nis, Nis, Serbia

Purpose: Tuberous sclerosis complex (TSC) is frequently associatedwith refractory seizures and development delay in children. Our purposeis to analyse epilepsy, AEDs (antiepileptic drags) therapy and cognitivedevelopment in adult patinets with TSC.

Method: We revised data of 3 patients with TSC (diagnostic criteriarevised by Gomez, 1999), with respect to the onset, type of epilepsy, neuroi-maging, cognitive and mental alteration (using the Griffiths Mental Devel-opment Scales, 1996. god. Revison), response to antiepileptic therapy.

Result: First patient is a 47 year old women, with typical skin abnormal-ities: hypomelanotics macules (more than three), shagreen patch, non-traumatic peringual fibromas and typical three types of brain tumors: cor-tical tubers, subependymal nodules and subependymal giant- cell astroci-tomas. She has low cognitive potentials and refractori partial epilepsywith secondary generalisation. Second patient is 25 year old man, with li-tle skin abnormalitis (hypomelanotics macules and periungual fibromas),typical brain tumors (cortical tubers, subependymal giant-cell astrocito-mas), low cognitive potencials end refractori partial epilepsy without sec-ondary generalisation. Third patient is 51 year old women with facialangiofibromas and typical three types of brain tumors (cortical tubers,subependymal nodules and subependymal giant- cell astrocitomas), lowcognitive potentials and refractori partial epilepsy with secondary gener-alisation.

Conclusion: We discussed clinical caracteristic, diagnostic and thera-peutic diferences. All patients have multiple lesions. Epilepsy began aspartial seizures with secondary generalisation in 2 patients and one patienthad complex partial seizures. All patients have global intelectual impair-mant. One patient with monotherapy is seizure free while 2 patients withpolytherapy have a reduction of seizure frequenty and intensity.

p282MESIAL TEMPORAL LOBE EPILEPSY AS A NEURO-PSYCHIATRIC SYNDROME OF SYSTEMIC LUPUSERYTHEMATOSUST. Toyota, N. Akamatsu, A. Tanaka, T. Shouzaki, and S. TsujiUniversity of Occupational and Environmental Health School ofMedicine, Kitakyushu, Japan

Purpose: Different types of seizures are grouped together without dis-tinction from epilepsy in the standard nomenclature and case definitionsfor neuropsychiatric syndromes of systemic lupus erythematosus(NPSLE) which has developed by the American College of Rheumatol-ogy. We aimed to investigate the types of seizures and epilepsy associ-ated with systemic lupus erythematosus (SLE).

Method: We searched the medical records at a tertiary referral center toidentify a cohort of epilepsy patients with SLE who were treated betweenJanuary 2000 and August 2011. We analyzed the clinical and immuno-logical profile of these patients, their seizure and epilepsy classifications,electroencephalography and MRI assessments, and the treatment admin-istered for epilepsy and SLE.

Result: Seventeen patients with SLE and epilepsy were identified.Seven patients had mesial temporal lobe epilepsy (MTLE), 8 had epi-lepsy secondary to stroke, and 2 had generalized epilepsy. Of the 7patients with MTLE, temporal spikes were noted in all patients on EEGand, MRI findings suggesting hippocampal sclerosis was noted in 4.Clobazam and levetiracetam were effective in treating 3 patients, and 1underwent amygdalahippocampectomy.

Conclusion: MTLE may be a characteristic manifestation of NPSLE.Most previous reports indicate that generalized seizures occurs often epi-lepsy in SLE, and a few reports indicate that partial or focal seizures arefrequent. However it is possible that most of generalized seizures in SLEreported before could in fact be focal epilepsy with secondarily general-ized seizures. MTLE is therefore an important differential diagnosis inNPSLE patients with seizures.

Semiology, Aetiology and classification 7Monday, 01 October 2012

p283AN ASSESSMENT OF THE INTER-OBSERVER RELI-ABILITY OF THE DEFINITION OF DRUG-RESISTANTEPILEPSY PROVIDED BY THE INTERNATIONAL LEA-GUE AGAINST EPILEPSYL. H. Ronquillo, L. Hernandez-Ronquillo, R. S. Topete, andS. BuckleyUniversity Of Saskatchewan, Saskatoon, Canada

Purpose: To evaluate the inter-observer reliability of the definition ofdrug–resistant epilepsy provided by the International League AgainstEpilepsy (ILAE).

Method: We randomly selected ninety-seven charts from 700 availablefrom the epilepsy clinic of the Royal University Hospital in the provinceof Saskatchewan, Canada (1 million population). Two independent chartreviewers underwent training regarding the four definitions of intractableepilepsy used in this study. Both individuals performed a small pilot with10 charts. None of the reviewers knew the patients and the evolution ofthe cases. We used the definition of drug-resistant epilepsy published byKwan and Brodie, Berg, Camfield and the one provided by the ILAE.The reviewers abstracted demographic data, diagnostic of epilepsy, clas-sification, evolution and medications. After the extraction of the neces-sary clinical information the four definitions were applied. Charts werereviewed with less than two months difference between reviewers toavoid misclassifications of patients over the time. Kappa was used tocompare the agreement between observers.

Results: The kappa for the Berg's definition was 0.56 (moderate), for theKwan and Brodie's definition was 0.58 (moderate), for the Camfield'sdefinition 0.69 (substantial) and for the definition of the ILAE was 0.77(substantial). Other analysis will be shown in the meeting.

Conclusion: The definition of drug-resistant epilepsy provided by theILAE showed the best agreement between observers. Both observers con-sidered that the definition of the ILAE was more complex to extract thanthe other three definitions due to the need of more information.

p284EPILEPSY AMONG THE STUDENTS OF �ANAKKALEONSEKIZ MART UNIVERSITYH. I. Ozisik Karaman, C. Bakar, and Y. DegirmenciCanakkale Onsekiz Mart Universitesi, Canakkale, Turkey

Purpose: Aim of this study was to investigate the frequency epilepsyamong the students of Canakkale Onsekiz Mart University.

Method: This sectional epidemiological study was performed on 4762of the 19988 Canakkale Onsekþz Mart University students in 2007–2008education period. Participants who answered ‘‘epilepsy’’ to the question‘‘Do you have any disease disgnosed by a doctor?’’ in a questionnaireincluding 4 subgroups were detected. Data were transferred to Epi-InfoVersion 6.0 statistics program and controlled data were analyzed in SPSS15.0 statistics program.

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Result: Fifty three point one percent of the students were female, 46.9%were male. Mean age was 20.4 € 2.1 years. Twelve (0.3%) students hadepilepsy diagnosis. Among these, 66.7% were female (n = 8), 33.3% (n =4) were male and the mean age was 20.8 € 1.8 years. Conclusion: In ourstudy, epilepsy was detected in 0.3% of the students (n = 12).

Conclusion: We didn’ t encountered any data for this age group in ourliterature review for epilepsy which has a variable frequency for age andcounttries. Thus, we considered that it would be epidemiologically signif-icant to share the results of our cross sectional study.

p285KNOWLEDGES AND BELIEVES OF PARENTS OFCHILDREN AND ADOLESCENTS WITH EPILEPSYB. Desnous, M. Milh, and S. AuvinRobert Debr� Hospital, Paris, France

Purpose: We conducted a survey in order to determine the level ofknowledge that parents of children with epilepsy have about epilepsy:what the epilepsy is for parents, we wanted to assess if they know howepilepsy's diagnosis is made. This study aimed to know the endpoints ofseizure's severity, the seizure's trigger, and the concerns during seizurefor parents. This study also aimed to highlight the impact of epilepsy inlifestyle of children and their parents.

Method: We conducted a qualitative survey, based on semi-structuredinterviews with parents of children with epilepsy between April andNovember 2010 in paediatric neurology department in 4 French univer-sity hospitals: Amiens, Marseilles, Nancy and Robert Debr� Hospital(Paris). Physicians conducted all the interviews. Parents of children withepilepsy were interviewed: 34 relatives aged 0 to 6 years, 38 relativesaged 7 to 12 years and 34 relatives aged more than 12. In total 106 inter-views were conducted.

Result: This study allows assessing the knowledge and believes of par-ents of children and adolescents with epilepsy and showed that knowl-edge of epilepsy among parents was generally limited. On average 34%of parents were unaware of their children's cause of epilepsy. Regardingto the endpoints of seizure's severity, the main criteria for all parents isthe duration of the seizure. The anti epileptic drugs have a positive imageto parents; they are with psychological support and lifestyle the threemain points of their child's treatment. Parents confirm that epilepsy has astrong impact on their child's lifestyle.

Conclusion: So many patients, parents of children with epilepsy are notwell informed about their disorder. There is slightly a need for educa-tional intervention to optimize self-management strategies. An under-standing of preseizure activity from the patients’ and carers’ perspectivehas great utility if the information can be combined with more objectivedata to identify gaps in patients’ and carers’ knowledge, which can thenbe used to develop education and intervention programs. Parents are reas-sured by a medical team that treats the ‘‘whole child’’ and not just epi-lepsy.

p286ON THE ORIGIN OF CORNU AMMONIS (AMMON'SHORN)I. IniestaThe Walton Centre NHS Foundation Trust, Liverpool, UK

Purpose: To investigate the origin of the term Cornu Ammonis (Am-mon¢s horn), introduction in medical literature and current meaning.

Method: As primary historical sources, Greek and Roman coins areessential archaeological remains that inform about the myths and gods ofClassical Antiquity, from the arrival at Rome of a snake shaped godAesculapius to save the Italians from the plague to invocations of major

deities such as Apollo the physician or the supreme Egyptian god Am-mon (the occult). Greek and Roman deities and their artistic representa-tion date indeed back to Ancient Egyptian times. Depicted with a ram¢shorn, Ammon was adopted by the Greeks as Zeus and later by theRomans as Jupiter. A transition that can be found in Greek coinagedevoted to Alexander the Great as well as in provincial Roman coinsstruck under Claudius.

Result: Inspired by the Renaissance school of Padua French anatomistscontinued to recover gods and myths of Classical Antiquity during theEnlightenment, renaming brain structures like the curve shaped innerportion of the temporal lobe as Cornu Ammonis. Among the mostremarkable contemporary neuroscientists who studied this hidden part ofthe brain outstands Cajal and his disciple Lorente de N�, who describedthe tri-synaptic circuit and the different CA (Cornu Ammonis) fieldswithin. CA1 is also known as Sommer¢s sector to acknowledge the latterdescription of mesial temporal sclerosis in temporal lobe epilepsy.

Conclusion: Ancient Greek and Roman coinage illustrate the role thatmyths and gods of Classical Antiquity keep playing in modern neurology.

p287AUDIT OF LOCAL NEUROPATHOLOGY PRACTICE INSUDEP AUTOPSIESM. Thom*, J. Liu*, J. W. Sander�, and S. M. Sisodiya�

*UCL, Institute of Neurology, London, UK; �Heemstede,Netherlands; and �UCL Institute of Neurology, London, UK

Purpose: There is an urgent need to understand the underlying mecha-nisms of sudden and unexpected death in epilepsy (SUDEP). Researchbased on post mortem (PM) brain collections may identify novel patho-logical and molecular mechanisms. This necessitates collection of a suffi-cient numbers of adequately sampled cases with complete clinical andpost mortem reports.

Method: We audited all epilepsy PMs at our centre for the completenessof data and regional brain sampling. We re-classified SUDEP casesaccording to revised definitions [Epilepsia 2011]. Questionnaires werealso sent to local general histopathologists (HP) regarding current prac-tice in epilepsy related deaths.

Result: We identified 62 SUDEP PMs (from 1991 to 2011), the majorityreferred cases for neuropathology examination. The median age at deathwas 24 years (range 2–79 years); 38 in males. The few cases with inade-quate regional brain sampling were those where the whole brain had notbeen fixed. Neuropathological changes were identified in the majority ofcases, hippocampal sclerosis the commonest finding in 25. Cases werere-classified as ‘possible SUDEP’ where full PM report was lacking orcontributing cause of death identified. Reponses from HPs indicated thatof those that conduct PMs, 70% virtually never retain the whole brain inepilepsy related deaths.

Conclusion: Systematic sampling in SUDEP brain demonstrates fre-quent neuropathological abnormalities and provides a useful researchresource. We highlight the importance of complete PM reports for correctclassification SUDEP and the need to increase awareness among HPs ofthe value of a complete neuropathological examination.

p288FUNCTIONAL ASYMMETRY OF THE BRAIN ANDLATE COMPONENTS OF EVENT-RELATED POTEN-TIAL P300O. S. Ivetic, and V. VasicMedical Faculty, Novi Sad, Serbia

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Purpose: The aim was correlation of the brain lateralization and vari-ables of cognitive P300 potentials during the usage of arms among right-handed girls.

Method: 60 right-handed girls, age 20–24, participated in investigation.First group: strong expressed right-hand girls; second group: moderatelyexpressed right-hand girls; third group: right-hand learned girls.

The research workers were using the "oddball’’ paradigm with twotones:"standard’’ and "expected-target’’. The subjects got instructions topress a button, as fast as they can, whenever they hear the ‘‘expected’’tone. The response was measured with the use of the right hand (first-recording) and left hand (second-recording). P300 evoked potentialswere registered above Fz and Cz area.

Result: It was shown that subjects with higher degree of dominance ofthe left brain hemisphere have significantly shorter latencies and higheramplitudes of P300 when the dominant hand was used, while the subjectswith weak or average degree of dominance of the left brain hemisphereshow no significant difference. Cognitive P300 amplitude waves arehigher above central regions independently of the hand used. Also, sub-jects with higher degree of dominance of the left brain hemisphere hadshorter RT but the difference was not statistically significant. The numberof false response was higher in right-hand learned girls.

Conclusion: The hemispheric dominance has influence on the event-related potential.

p289PHARMACO-RESISTANT EPILEPSY-CASE PRESEN-TATIONC. Panea, G. D. Vanghelie, N. Ploscutanu, and G. CioaraEmergency University Hospital ‘‘Elias’’, Bucharest, Romania

Purpose: Drug-resistant epilepsy is defined as the persistence of sei-zures despite adequate antiepieleptic treatment with at least two first-lineAEDs, monotheraphy or in combination, using different mechanisms ofaction and at maximum tolerated doses.

Method: Pseudoresistance must be also taken into consideration, inwhich seizures persist because the underlying disorder has not beenappropriately diagnosed and treated or misdiagnosis of epilepsy withother conditions that mimic epileptic seizures (vasovagal syncope, car-diac arrhythmias, metabolic disturbances, transient ischemic attacks,migraine, psychogenic seizures that are estimated to account for morethan 25% of adult cases of apparently drug-resistant epilepsy).

Result: We present the case of a 33 years old male, diagnosed with focalepilepsy with complex partial seizures and secondary generalization thatwas considered to be resistant to antiepileptic drugs, with positive familyhistory (his brother has idiopathic primary epilepsy), cerebral imagerythat revealed hippocampal asimmetry and right frontal angioma and aninterictal EEG that did not allow a certain diagnosis as regarding the typeof epilepsy. Ictal recordings showed an EEG ictal pattern with its onseton the left temporal and fast propagation to the right fronto-temporal withsecondary generalisation.

Conclusion: Possible clinical predictors of drug resistance have beenidentified including a high number or frequency of seizures in the earlyphase of the disorder and a presence of a structural cause of epilepsy, par-ticularly hippocampal sclerosis. For this case, it is imposed to asses thebenefit-risk of treatment alternatives that should also consider epilepsysurgery.

p290ANTI-EPILEPTIC THERAPY AND SLEEP RELATEDPROBLEMS IN GEORGIAN EPILEPSY PATIENTSL. Maisuradze*, L. Zhizhiashvili�, and S. Kasradze�

*I. Beritashvili Center of Experimental Biomedicine, Tbilisi,Georgia; and �Institute of Neurology and Neuropsychology,Tbilisi, Georgia

Purpose: Epilepsy is found in 0.88% of Georgian population. Sleep dis-orders are common conditions that frequently coexist with epilepsy. Thepresent study was aimed to identify insomnia and restless legs syndrome(RLS) in treated epilepsy patients (T) and newly diagnosed individualshaving epilepsy (UT).

Method: Among the 161 consecutive subjects admitted to the Instituteof Neurology and Neuropsychology, 119 had epilepsy diagnosis treatedwith antiepileptic drugs (AEDs) and 42 were newly diagnosed epilepsypatients never taken AEDs before. Sleep impairment index was filledout by 84 subjects (60, T and 24, UT), group 1, and the questionnairefor the RLS was completed by 77 subjects (59, T and 18, UT), group2. Data analysis was performed by SPSS statistical software, version13.0.

Result: Among the 161 consecutive subjects admitted to the Instituteof Neurology and Neuropsychology, 119 had epilepsy diagnosis trea-ted with antiepileptic drugs (AEDs) and 42 were newly diagnosed epi-lepsy patients never taken AEDs before. Sleep impairment index wasfilled out by 84 subjects (60, T and 24, UT), group 1, and the ques-tionnaire for the RLS was completed by 77 subjects (59, T and 18,UT), group 2. Data analysis was performed by SPSS statistical soft-ware, version 13.0.

Conclusion: These findings clearly indicated that the understanding therelationship between epilepsy and sleep disorders is important for thedeveloping of appropriate treatment strategy for the epilepsy patient.

p291NEUROAMINOACIDS STATE IN PATIENTS RECOVER-ING FROM TRAUMATIC BRAIN INJURY WITH CON-VULSIVE SYNDROMEI. I. Chernenko*, and N. Sych�

*Kharkiv Medical Academy of Postgraduate Education,Kharkiv, Ukraine; and �Institution, City, Russian Federation

Purpose: The aim of work was to study the content neuroaminoacids(NAC) in whey of blood patients with traumatic brain injury (TBI) with aconvulsive syndrome.

Method: Material and methods. We examined 42 patients with TBIat the age of 23 to 65 years. The level of NAC was determined inthe first days after TBI received. The first group consisted of 20persons moderate TBI with convulsive syndrome, mean age 53,39 €0,42 years, the second – 22 people with mild TBI with a convulsivesyndrome, mean age 52,71 € 0,49 years. The groups were compara-ble in age, sex.

Result: The results. The study revealed that patients with mild TBIlevel of excitatory NAC (glutamic – 1,145 € 0,24 mg, aspartic –0,228 € 0,05 mg) were significantly higher than in patients withmoderate TBI with convulsive syndrome (0,805 € 0,07 mg and 0,164€ 0,02 mg, respectively), p < 0,05. At the same time, there was atrend to an increase in brake NAC in patients with mild TBI with aconvulsive syndrome compared with patients with moderate TBI witha convulsive syndrome (glycine – 1,427 € 0,13 mg and 1,345 € 0,19mg respectively, proline – 1,556 € 0,24 mg is the 1,211 € 0,17 mg,respectively), p > 0,05.

Conclusions: Thus, patients with mild TBI with a convulsive syndromemarked by an imbalance of NAC: NAC increase in excitatory (glutamate,aspartate) and a tendency to increase the level of brake NAC (glycine,proline) compared with patients with mild TBI with convulsive syn-drome.

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p292EPILEPSY AND NEUROCYSTICERCOSIS IN NORTHWEST CAMEROON: A SEROLOGICAL STUDYA. J. Akeneck, C. O. Snead, I. E. Elliott, N. K. Alfred,A. S. Angwafor, L. C. Cockburn, I. T. Takougang, and M. L. LouAssociation of Orphans and the Disabled ASODI Cameroon,Mankon Bamenda, Cameroon

Purpose: The prevalence of epilepsy in Cameroon is higher than that ofthe industrialized?world. The prevalence of epilepsy appears to be espe-cially high in the Momo Division of the Northwest Province of Camer-oon. Because neurocysticercosis is a major cause of epilepsy indeveloping countries, we sought to test the hypothesis that those patientsin Momo who have epilepsy have a higher percentage of seropositivity toTaenia solium than a matched control population.

A case control study was conducted in the Momo sub-division of Ngiewhich has nineteen villages. Epilepsy patients were recruited from theepilepsy clinics in Ngie and control subjects were randomly selectedfrom members of the Ngie villages. An adapted form of a previously vali-dated screening questionnaire was applied by trained field workers toidentify potential cases of epileptic seizures to be included in the study.Blood samples were taken from all consenting individuals by fingerprick, stored in StabilZyme Select, and assayed for antibodies to Taeniasoleum as described.

Method: This study was carried out under the ethical precepts found inthe World Medical Association Declaration of Helsinki (http://www.wma.net/e/policy/b3.htm). Ethics approval was obtained from theResearch Ethics Board (REB) of the Hospital for Sick Children, Toronto,Canada, the National Ethics Committee, Cameroon, and the local districtethics committee, Alpha Royal Clinic REB. Community consent was firstobtained by having medical health volunteers explain the goal of thestudy to village traditional and administrative and health authorities.Community information sessions were then conducted, the purpose ofwhich was to allow individuals to discuss their questions and concerns.Village coordinators, who helped study participants to complete the ques-tionnaires, were trained on how to obtain informed consent. In addition,the coordinators determined who could read. Ngie language is not writ-ten. Therefore, to make things clear a translated version of the informedconsent was made on an audiotape and played where necessary. Follow-ing these community meetings, potential subjects and controls were pro-vided further information and if they agreed to participate, consent forthe administration of the questionnaire and blood sampling was obtained.

Result: We accrued 249 patients with epilepsy and 245 age-matched con-trols. The number of patients with epilepsy who participated in this studyrepresent about 75% of the total number of seizure patients in Ngie wherethe population is around 40,000 inhabitants. The mean age of control sub-jects was 17.5 years and that of the seizure population 18.8 years (P > 0.1).There were 53% male and 47% female in the seizure group and 57% maleand 43% female in the control group (P > 0.1). Seizure onset was at 11.64yrs. Sixty-eight percent of patients had generalized convulsive seizureswith 25% having localization-related epilepsy with secondary generalizedseizures. There was no significant difference between the control and sei-zure populations in seropositivity to Taenia soleum which was 4.9% in thecontrol group vs. 5% in the seizure group. These data demonstrate thatthose patients in the Ngie sub-division of Momo who have epilepsy do nothave a higher percentage of seropositivity to Taenia solium than a matchedcontrol population and make it highly unlikely that neurocysticercosisplays a causative role in the increased prevalence of epilepsy in the MomoDivision of the Northwest Province of Cameroon. Supported in part byThe Bloorview Children's Hospital Foundation.

Conclusion: This data does not support the hypothesis that those indi-viduals in Ngie sub division of Momo Division who have epilepsy have ahigher percentage of teania solium than a matched contro population.

The data makes it highly unlikely that neurocysticercosis plays a caus-ative role in the increased prevalence of epilepsy in the sub region.

These results and preveiousely published results suggest that the highprevalence of epilepsy reported in some areas in Cameroon could beattributed to a complex yet to be elucidated, interplay of several factors.

SEMIOLOGY, AETIOLOGY AND CLASSIFICATION 8MONDAY, 01 OCTOBER 2012p293HEALTH-RELATED QUALITY OF LIFE OF PATIENTSIN THE PATIENTSLIKEME EPILEPSY COMMUNITYC. De La Loge*, S. Dimova�, K. Mueller�, T. Durgin§,M. Massagli–, and P. Wicks–

*UCB Pharma, Brussels, Belgium; �UCB Pharma SA, Brussels,Belgium; �UCB Pharma Monheim, Monheim, Germany; §UCBPharma SA, Smyrna, GA, USA; and –PatientsLikeMe Inc,Cambridge, MA, USA

Purpose: To describe health-related quality of life (HRQoL) of mem-bers of the PatientsLikeMe� Epilepsy Community and identify predic-tors of poor HRQoL.

Method: Analyses were based on patient-completed information: socio-demographic and disease characteristics, treatments, symptoms, seizureoccurrence, Quality of Life in Epilepsy (QOLIE-31/P) and Hospital Anx-iety and Depression Scale (HADS).

Result: By May 2011, 1025 patients had completed the QOLIE-31/Pand HADS and were included in this analysis (mean age 37.5 years;72.7% female; mean epilepsy duration from diagnosis 17.5 years).HRQoL was highly correlated to HADS Anxiety and Depression scores.Poor HRQoL was more likely in patients reporting (Odds Ratio [95%Confidence Interval]; multivariate logistic regression): i) moderate/severe problems concentrating (3.19 [2.00–5.08]), depression (2.61[1.77–3.85]), memory problems (2.04 [1.29–3.24]), fatigue (1.75 [1.12–2.71]), anxiety (1.49 [1.00–2.22]); ii) severe side effects (2.34 [1.39–3.92]); iii) at least one tonic-clonic seizure during the 4 weeks beforeQOLIE-31/P completion (2.72 [1.65–4.50]); iv) age 25–50 years (1.77[1.01–3.11] vs age 0–25 years) and v) shorter epilepsy duration (£1 year2.25 [1.23–4.13]; 1–10 years 1.70 [1.12–2.58]; both vs >10 years).Patients on polytherapy with newer antiepileptic drugs (AEDs) were lesslikely to report poor HRQoL than patients on polytherapy with olderAEDs (0.29 [0.11–0.74]).

Conclusion: These analyses indicate that moderate/severe problemsconcentrating, depression, and the occurrence of generalized tonic-clonicseizures and severe side effects were the most predictive factors of poorHRQoL in the PatientsLikeMe Epilepsy Community. These results sug-gest that a holistic approach beyond seizure control should be consideredwhen treating people with epilepsy.

p294EVALUATING EPILEPTIC POPULATION AND ITSCOST IN THE SOUTH OF SPAING. Garcia Martin, M. I. Chamorro MuÇoz, M. Romero Acebal,and F. Perez ErrazquinVirgen de la Victoria Hospital, Malaaga, Spain

Purpose: Epilepsy is a common disorder around the world and a bigeffort in order to know the features of the population with this illnesss isbeing done nowadays. Although there is quite information of some partsof Europe, information from the south west is not enough. Moreoverknowing the cost of the illness is really interesting in the current eco-nomic situation. The purpose weas to evaluate the features of people withepilepsy in Malaga (Spain) and the cost of visiting this population in aGeneral Hospital.

Method: To describe the features of all the patients with active epilepsyor epilepsy on treatment visited in Virgen de la Victoria Hospital inMalaga, in one of the Epilepsy Offices. To calculate the cost of epilepsytaking into account number of visits, tests made and the consumption ofdrugs in one year but not emergency assistance.

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Result: 515 patients were selected of a total of 2282 patients visited inall the Epilepsy Offices. Features of patients and the costs of illness arepresented. We compare our results with those from other studies in Eur-ope.

Conclusion: The features of the epileptic population in Malaga are simi-lar to those from other parts of Europe. The cost of epilepsy in our Hospi-tal is quite similar to that of other studies in Europe. The main cost inHospitla for this population depends on the nmumber of visits to the neu-rologist and on the chronic treatment.

p295PSEUDO-REFRACTORY EPILEPSY: FOLLOW UP 105PPATIENTSG. Kutlu, A. Erdal, Y. BiÅer Gçmceli, and L. E. InanMinistry of Health, Ankara Research and Training Hospital,Ankara, Turkey

Purpose: Pseudo-Refractory epilepsy is defined as seizures inade-quately treated due to incorrect diagnosis, use of incorrect and/or lowdose antiepileptic drug (AED) and poor compliance of patients. The aimof this was to investigate the patients with pseudo-refractory epilepsy.

Method: The files of two thousand nine hundred twenty patients werereviewed by the same neurologist and the patients with pseudo-refractoryepilepsy were eliminated. The patients who had not enough control ofseizures despite the two different AED treatment before follow up in ourdepartment and had no seizure at least one year after the revision of thediagnosis and/or treatment of epilepsy, were accepted as pseudo-refrac-tory. Demographic data, medical and epilepsy history, electroencepha-lography (routine and/or induction of seizure by using normal saline orself induction), home video and neuro-imaging findings were examined.

Result: One hundred five patients were included in this study. The meanage was 29 € 11.53. Seventy-four patients (70.5%) was female, theremaining 31 patients were male. Incorrect diagnosis of epilepsy wasobserved in 57 patients (forty seven non-epileptic psychogenic seizure,seven syncope, two sleep disorder, one hypoglycemia). Epilepsy classifi-cation and treatment error was present in eighteen patients. Forty twopatients had poor compliance of treatment and inappropriate life style.Twelve patients had more than one reason for pseudo-resistance (togetherwith classification and/or treatment error, and poor compliance).

Conclusion: Pseudo-refractory patients are still a big problem in ourclinical practice. Differentiation of pseudo-refractory and true refractoryepilepsy is so important for avoiding unnecessary treatment approachand future management of true refractory epilepsy.

p296WHAT REALLY MATTERS TO PEOPLE WITH EPI-LEPSY? RESULTS FROM AN INTERNATIONALPATIENT SURVEYJ. A. Cramer*, S. Dupont�, M. Goodwin�, and E. Trinka§

*Yale University School of Medicine, Houston, TX, USA; �Piti�-SalpÞtri�re Hospital, Paris, France; �Northampton GeneralHospital NHS Trust, Nothampton, UK; and §Paracelsus MedicalUniversity, Salzburg, Austria

Purpose: To conduct an international survey amongst people with epi-lepsy, in order to define issues of importance in their daily lives, corre-lated with duration of epilepsy, age, as well as other characteristics.

Method: A web-based survey, translated into 12 languages, was distrib-uted through the International Bureau for Epilepsy member associationwebsites and via email. The predominantly multiple-choice question-naire focused primarily on personal experiences of the impact of

epilepsy; individual epilepsy management; and aspects of epilepsy thatmatter most to people with epilepsy. During July-October 2011, 513 peo-ple with epilepsy (63.8% female; ages ranging from <16 to >65 years)from 29 countries completed the survey. All survey responses were anon-ymised and collated in a central database for analysis.

Result: Over 60% of respondents considered their seizures to be suffi-ciently controlled, but >40% still had seizures at least every month and>40% would have changed medication to improve seizure control.Approximately 70% of respondents suffered medication side effects and>30% would have changed medication to reduce side effects; however,almost 25% had never proactively discussed side effects with their doc-tor/nurse. Different side effects mattered more/less to different respon-dents (e.g. weight gain tended to matter more to females than males).Approximately 30% of respondents admitted missing medication at leastonce a month.

Conclusion: The survey provides valuable insights into the real chal-lenges and needs of people with epilepsy and may play a part in shapingfuture management strategies. Supported by Eisai.

p297SOMATIC CO-MORBIDITIES ARE A MAJOR ISSUE INPEOPLE WITH EPILEPSYJ. Novy, G. Bell, S. M. Sisodiya, and J. W. SanderUCL Institute of Neurology, London, UK

Purpose: People with epilepsy seem to have more concomitant medicalconditions than the general population. Co-morbid conditions may be afactor in the increased risk of premature death seen in people with epi-lepsy, including those in remission. While there are several studiesexploring epidemiological patterns of psychiatric co-morbidities in epi-lepsy, less is known about somatic co-morbidities. We aimed to explorethe epidemiology of somatic co-morbidities in people with epilepsy.

Method: We collected clinical, demographic and somatic co-morbiditydata in >2000 consecutive people with drug-resistant epilepsy assessed ata tertiary centre and in 1350 patients with epilepsy in the community.Underlying causes of epilepsy were not taken as co-morbidities, neitherwere symptoms of the cause.

Result: Somatic co-morbidities were found in 48% of people with drug-resistant epilepsy and in 35% in the community (p < 0.0001). People withdrug-resistant epilepsy were younger (median age 35) than those in thecommunity (median age 45). Somatic co-morbidities were more frequentthan psychiatric ones (25% in people with drug-resistant epilepsy, 10%in the community). Preliminary analysis suggests that older age, olderage at epilepsy onset and no identifiable cause may be independent pre-dictors of a higher burden of co-morbidities.

Conclusion: This seems to suggest that epilepsy itself influences theoccurrence of somatic co-morbidities. Somatic co-morbidities should notbe overlooked as they appear as frequent as psychiatric co-morbidities.The reasons for this are not entirely clear as this stage but commongenetic predisposition cannot be discounted. Further studies are urgentlywarranted.

p298DEVELOPMENT AND PILOT OF A QUESTIONNAIREFOR REPORTING EPILEPSY-RELATED DEATHSL. Flores*, K. Osland�, J. Hanna�, and L. Nashef**King's College Hospital, London, UK; and �EpilepsyBereaved, Oxfordshire, UK

Purpose: Aim: To assess the applicability of a detailed questionnaireadministered by a lay person to bereaved relatives on sudden death inepilepsy.

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Method: After basic training, the questionnaire, based on a previouslyused tool, was administered through telephone interviews carried out bytwo workers from Epilepsy Bereaved with relatives of deceased patients.

Result: The survey obtained complete and detailed data on most itemsincluded. SUDEP was stated as the cause of death in 17 of 31 transcribedinterviews, three with reportedly mild epilepsy, four with relativelyrecent onset of seizures and three witnessed cases. Three relativesreported having received some information about SUDEP from the medi-cal team. More than half the families were not contacted by the medicalteam after death and counselling was offered to 15 only.

Conclusion: The applicability of administering this questionnaire by alay person familiar with the field was demonstrated. Data obtained wasassessed as high quality with limited modifications to the questionnaireneeded. This tool may be useful for a SUDEP register. The increase indeath certificates listing SUDEP in 54.8% of cases compared to 3.8% (1/26) in an older study of circumstances of death in SUDEP carried out 16years ago suggests a greater awareness by pathologists and coroners. Onthe other hand, counselling and a meeting with the treating specialistwere reportedly infrequently offered.

p299PLACE OF VIDEO-EEG MONITORING IN DIAGNOSISAND MANAGEMENT OF IDIOPATHIC GENERALIZEDEPILEPSYL. Iuhtimovschi*, S. Groppa*, and A. Bunduchi�

*State Medical and Pharmaceutical University ‘‘NicolaeTestemitanu’’, Chisinau, Moldova; and �Medical Center‘‘Excellence’’, Chisinau, Moldova

Purpose: To appreciate electro-clinical correlations in patients withactive focal epilepsy treated unsuccessfully with Carbamazepine.

Method: Our study included 32 patients (21 women and 11 men), agerange 18–54, diagnosed with epilepsy 1,5 to 30 years ago, previouslyexamined only by routine EEG (10–15 minutes). All patients were evalu-ated by video-EEG monitoring 3 to 6 hours.

Result: 13 patients had EEG electro-clinical patterns ‘‘petit mal’’ typicalfor absence epilepsy. 5 patients revealed electro-clinical patterns of myo-clonic seizures. 14 patients presented subclinical discharges of typicalgeneralized spike-wave, poly-spike-wave, and sharp wave-slow waveactivity. All changes appeared on preserved general cortical activity.Accordingly patients were divided in groups: I group – Absence epilepsy,II group – Juvenile Myoclonic Epilepsy, III group – Idiopathic General-ized epilepsy. In all patients treatment was substituted with Valproate (I,II, and III group) or Ethosuximide (I group). Video-EEG monitoring wasrepeated 4 month later. In 100% cases EEG revealed substantiallyreduced epileptiform activity. Follow-up period of 1,5 to 3 years showedclinical remission in 3 patients (I group), 2 patients (II group), and 7patients (III group); while electro-clinical remission – in 8 patients (Igroup), 3 patients (II group) and 5 patients (III group).

Conclusion: Routine EEG investigations are insufficient for a cleardiagnosis of idiopathic generalized epilepsy, because myoclonic andabsence seizures are often neglected by patients and observers. Whenaddressed to specialist patients present generalized seizures incorrectlydiagnosed as secondarily generalized and treated with Carbamazepine.Video-EEG monitoring helps to establish epileptic patterns, correct diag-nosis and initiate adequate treatment.

p300PGES IS MORE FREQUENT IN CONVULSIVE SEI-ZURES ARISING FROM SLEEPR. J. Lamberts*, S. Laranjo�, S. Kalitzin*, D. Velis*, I. Rocha�,J. W. Sander*, and R. D. Thijs�

*SEIN-Epilepsy Institute in the Netherlands Foundation,Heemstede, The Netherlands; �Institute of Neurology, London,UK; and �UCL Institute of Neurology, London, UK

Purpose: Postictal generalized EEG suppression (PGES) seems to be apathophysiological hallmark in the ictal recordings of sudden unexpecteddeath in epilepsy (SUDEP). It has recently been suggested that the pres-ence and duration of PGES might be predictors of SUDEP risk [1]. Littleis still known about its aetiology.

Method: A retrospective case-control study was conducted in 50 peoplewith convulsive seizures (CS) registered on digital video-EEG. Per indi-vidual one CS was reviewed for the presence and duration of PGES bytwo independent assessors: 37 (74%) patients showed PGES and 13(26%) did not. Pre- and postictal heart rate (HR) and frequency domainmeasures of heart rate variability (HRV) including the ratio of low versushigh frequency power were analyzed . The relation between PGES andperi-ictal autonomic changes was evaluated, as well as its associationwith several clinical variables.

Result: PGES was neither associated with peri-ictal HR (mean HR dif-ference between PGES+ and PGES- seizures: -5 bpm, 95% CI -13 to +3bpm) nor HRV change. There was no relation between duration of thetonic-clonic phase of the seizure and PGES. Patients with PGES weremore likely to be asleep prior to seizure onset (OR 4.7, 95% CI 1.2–18.3)and had a higher age of onset (median age; 15 vs. 5 years).

Conclusion: PGES was not associated with substantial changes in mea-sures of cardiac autonomic instability but more prevalent in CS arisingfrom sleep. PGES might be an expression of excessive neuronal inhibi-tion acting as a seizure termination mechanism.

Reference: 1.Lhatoo SD, Faulkner HJ, Dembny K, Trippick K, JohnsonC, Bird JM. An electroclinical case-control study of sudden unexpecteddeath in epilepsy. Ann Neurol 2010; 68(6): 787–796.

p301AUTOMATIC ABNORMAL WAVES DETECTION FROMTHE ELECTROENCEPHALOGRAMS OF EPILEPSYCASES TO SORT OUT THE SPIKES, THE SHARPS, THEPOLYPHASE BASED ON WAVELET TRANSFORMA-TION CROSSCORELATIONS. NoertjahjaniUNDARIS, Semarang, Indonesia

Purpose: Wavelet transformation is applied to electroencephalogramrecords from epileptic patients. The temporal sharpness associated withinterictal spikes at different resolutions is observed and two ways for rep-resenting the multiresolution sharpness of the spikes.

Method: Patient consist of 349M, 234F, ages 3–68 years. Clinical sta-tus: epileptic (136M, 80F: EEG with spike;47M, 40F without); clinicalstatus: nonepileptic: (98M, 65F EEG with spike; 68M, 49F without).Numerical data were acquired with EEG dump diagnostic Biologic sys-tem at Sarjito hospital Yogyakarta etc, 2002–2011. The wave compo-nents were sorted out according to their amplitudes, time span betweenzerocrossings, and different frequencies wavelet.

Result: The experimental results the spikes show consistent large out-puts throughout the wavelet set, they have sharpness at several differentresolutions. Utilizing the hardware and software facilities at hand, mark-ing the starts and ends of abnormal waves could be done with +100 lVthreshold. The zerocrossings and crosscorelation detection could auto-matically distinguished according to the 20–70 ms time period for the‘‘spikes’’ (89M, 58F),70–120 ms for ‘‘sharps’’ (160M, 101F), and theexistence of multiple peaks for ‘‘polyphase’’(100M,75F).

Conclusion: The research carried out so far was to find the prospect ofthis digital signal processing on EEG waves to support the doctors’ workin this field.

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p302REFLEX MYOCLONIC EPILEPSY IN INFANCY: AMULTICENTER CLINICAL STUDYS. Matricardi*, A. Verrotti*, G. Capovilla�, C. D’Egidio*,R. Cusmai�, A. Romeo§, D. Pruna–, P. Pavone**,S. Cappanera��, T. Granata��, G. Gobbi§§, P. Striano––,S. Grosso***, P. Parisi��, E. Franzoni��, S. Striano§§§,A. Spalice��, R. Marino*, F. Vigevano�, and G. Coppola–––

*University of Chieti, Chieti, Italy; �‘‘C. Poma Hospital’’ ofMantova, Mantova, Italy; �‘‘Bambino Ges�’’ Children's Hospitalof Rome, Rome, Italy; §‘‘Fatebenefratelli e Oftalmico’’ Hospitalof Milan, Milan, Italy; –Azienda Ospedaliero Universitaria ofCagliari, Cagliari, Italy; **University of Catania, Catania,Italy; ��Ospedali Riuniti of Ancona, Ancona, Italy; ��IRCCSFoundation Neurological Institute C. Besta of Milan, Milan,Italy; §§‘‘Maggiore’’ Hospital of Bologna, Bologna, Italy;––Gaslini Institute, University of Genova, Genova, Italy;***University of Siena, Siena, Italy; ��‘‘La Sapienza’’University of Rome, Rome, Italy; ��University of Bologna, ‘‘S.Orsola-Malpighi’’ Hospital, Bologna, Italy; §§§Federico II’’University of Napoli, Napoli, Italy; and –––University ofSalerno, Salerno, Italy

Purpose: Reflex myoclonic epilepsy in infancy (RMEI) is a rare clinicalentity and most of the available evidence (Ricci S et al. Epilepsia1995;36:342–348; Giovanardi Rossi P et al. Brain Dev 1997;19:473–479; Caraballo R et al. Rev Neurol 2003;36:429–432), based on anecdoc-tal cases, are inconclusive regarding its evolution and prognosis. Wedescribe the clinical and electroencephalographic (EEG) features andlong-term cognitive outcome.

Method: We enrolled 31 children from 16 neuropediatric centers inItaly, who underwent periodical clinical and video-EEG evaluation. Cog-nitive assessment was performed in all patients using standardized psy-chometric tests according to their age.

Result: The age at onset ranged from 3 to 24 months of age. Seizureswere characterised in all patients by symmetric myoclonic seizures (MS),triggered by sudden unexpected acoustic (38.7%) or tactile stimuli (29%)or both (29%). Photosensitivity was absent in all patients. Spontaneousattacks were reported in 32.2% of the cases. Interictal EEG was normal inall cases. Ictal EEG showed generalized high-amplitude 3 Hz polyspikeand wave discharges, synchronous with brief rhythmic bursts of electro-myographic activity . Patients were re-evaluated after a period of 7.2 €5.6 years. The prognosis for seizure control was excellent in all cases andreflex MS disappeared spontaneously or after valproate treatment. Thecognitive outcome was excellent in 90.3% of children.

Conclusion: RMEI appears to be a variety of idiopathic generalized epi-lepsy with specific features that occurs in developmentally normal chil-dren, which should be classified as a distinct nosographic syndrome.


p303A NOVEL INTERNET ANIMATION SEIZURE SURVEYMAY BE AN EFFECTIVE SCREENING INSTRUMENTFOR POPULATION-BASED RESEARCHW. J. D’Souza, J. Freeman, S. Harvey, and M. CookThe University of Melbourne, Melbourne, Vic., Australia

Purpose: The conventional research method to screen for epilepsy iswith a written questionnaire administered door-to-door (WQ). Althoughthis enables comprehensive capture of undiagnosed and untreated cases,it is resource intense, insensitive to non-convulsive seizures and ineffi-cient for large-scale recruitment for aetiologic or prognostic studies. Ouraim was to ‘field test’ a novel digital animation seizure-screening ques-tionnaire that may be more suitable for community-based recruitment.

Method: We developed a series of high-resolution digital animationsdepicting visual sequences of young people with seizures (AQ) consist-ing of: tonic-clonic, simple partial motor, complex partial temporal lobe,absence and myoclonic. We administered AQ to parents of primary andsecondary school students and secondary school students by a speciallyconstructed website www.sparks.org.au. All students underwent epilepsyspecialist assessment (ESA) including EEG when indicated, to confirmthe diagnosis of epilepsy. AQ was repeated after first completion, to esti-mate repeatability.

Result: 206 AQ internet surveys were conducted (157 parental, 38 stu-dents) with all undergoing ESA: 8 screened positive with 3 confirmedcases of epileptic seizures, 2 of which were new. Both parental and stu-dent's surveys combined: sensitivity 1.00 (1.00–1.00), specificity 0.95(0.92–0.99), Youden's Index – a summary measure of sensitivity andspecificity – 0.95 (0.93–0.99). Surveying only parents improved specific-ity slightly without affecting sensitivity. Repeat survey (n = 62) demon-strated 100% concordance.

Conclusion: Although numbers are relatively small, early results sug-gest that AQ may be a more effective population-screening instrumentthan WQ. In addition, it should greatly improve efficiency as it can read-ily recruit individuals and households through devices that access the in-ternet rather than door-to-door.

p304AN COMPETENCY FRAMEWORK FOR ADULT EPI-LEPSY SPECIALIST NURSESY. Leavy*, M. Goodwin�, S. Higgins�, and V. Myson§

*Western General Hospital, Edinburgh, UK; �NorthamptonGeneral Hospital, Nothampton, UK; �Glocestershire RoyalHospital, Gloucester, UK; and §Cardiff and Vale NHS trust,Cardiff, UK

Purpose: Epilepsy affects approximately 600,000 people in the UK(UK) (Joint Epilepsy Council 2011). For over twenty years adult Epi-lepsy Specialist Nurses (ESNs) have been managing epilepsy and sup-porting people with epilepsy (PWE). However, despite this longassociation there are currently no guidelines for employers or stakehold-ers regarding the entry experience or qualifications when recruiting anadult ESN. The adult ESN competency framework attempts to addressthis. It also defines core competencies thought to be central to effectiveperformance and attempts to articulate progression from a novice special-ist nurse through to competent and ultimately expert specialist nurse. Inpractice this framework should provide practical and aspirational guid-ance for ESN's and for those involved in assessing their competence topractice.

Method: The Adult ESN Competency Framework has been developedby a UK-wide steering group of ESNs with a variety of experience, andreviewed by academics, and researchers. Literature reviews of relevanthealthcare policy, nurse training and epilepsy guidelines were under-taken. This work has been led by the Epilepsy Nurses Association(ESNA) and accredited by the Royal College of Nursing (RCN), with thesupport of Epilepsy Action to provide a patient perspective.

Result: The competency framework consists of nine dimensions: AKnowledge of Epilepsy B Clinical Management of Epilepsy C Indepen-dent Living D Joint Working/Professional Relationships E Personal Plan-ning and Organisation F Teaching Patients G Audit H Research IEpilepsy Surgical Management/VNS.

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Conclusion: The adult ESN competency framework provides practicaland aspirational guidance for ESN's and employers regarding entry andongoing qualifications, experience and clinical competence.

p305TREATMENT GAP OF EPILEPSY IN PAKISTAN: APOPULATION-BASED STUDYZ. Mogal, S. W. Akhtar, R. Malik, and H. AzizNational Epilepsy Centre, Jinnah Postgraduate Medical Centre,Karachi, Pakistan

Purpose: To assess any change in treatment gap status of epilepsy inPakistan following a countrywide intensive and sustained epilepsyawareness program.

Background: According to the population-based epidemiologic andknowledge, attitude and practice study of 1987, prevalence of epilepsy inPakistan was 0.98% with a treatment gap of 86%; lack of knowledge andwrong cultural beliefs about the condition being main reasons (Aziz H etal. Epilepsia 1994;35(5):950–958). Intensive and sustained countrywideepilepsy awareness through Comprehensive Epilepsy Control Pro-gramme of Pakistan is ongoing since 2001. Five years after initiation ofthis public awareness campaign, another population-based study was per-formed and treatment gap status re-assessed. We are presenting partresults of this study.

Method: A door-to-door population-based epidemiologic study wasconducted in urban and rural areas of Sialkot in northern Pakistan. Sam-ple collection was done by random block selection method in proportionto the population structure of the area. Questionnaire based on ICBERGprotocol (same as used in 1985–89 study) was applied.

Result: Of the 3780 people screened from 762 households, 55 (1.46%)had epilepsy. Of the 53 people with epilepsy (data on 2 is unsubstanti-ated), 30 (56.6%) were taking atleast one antiepileptic drug whilst 23(43.4%) were not taking any medications at the time of survey.

Conclusion: Treatment gap of epilepsy in Pakistan has decreased from86% to 43.4% after five years of intensive epilepsy awareness campaign,countrywide. With all other variables remaining constant, an intensiveand sustained public awareness campaign has been instrumental indecreasing the treatment gap.

p306WILLIAM RICHARD GOWERS 1845–1915: EXPLORINGTHE VICTORIAN BRAINA. ScottThe University of Queensland, Brisbane, Australia

Purpose: The Victorian neurologist William Richard Gowers was a cli-nician, researcher, writer, and teacher, whose prolific output included thetwo-volume Manual of Diseases of the Nervous System (1886 and1888),and numerous publications on epilepsy, culminating in The Borderlandof Epilepsy (1907) (which introduced this term into the medical litera-ture). In 1949 Macdonald Critchley wrote a ‘biographical appreciation’of Gowers in which he referred to the ‘peculiar dificulties in gatheringobjective material’ about a man ‘admired but not understood’.

Method: This more comphrehensive biography, to be published in 2012by Oxford University Press, is by Professor Ann Scott (Gowers’ great-granddaughter), and neurologists Professors Mervyn Eadie and AndrewLees. The aim of the authors has been to draw on newly-availableresources to re-examine Gowers’ life and his contributions to neurologi-cal science.

Result: The authors uncovered important new primary sources from theGowers family papers and other archives, including significant finds atthe National Hospital, Queen Square. Scott also transcribed the 83,000-

word shorthand diary Gowers kept when apprenticed to a country doctorin Essex in 1862–3. These discoveries have enabled the authors to offer afuller account of Gowers’ early professional development and later inter-ests, the social context within which he functioned, and his contributionsto the expanding neurological understanding of his day.

Conclusion: This new biography brings to a wide readership the life andwork of a great medical neurologist, offering additional insights on Vic-torian medicine more generally; and it makes available a rich store ofarchival material never previously published.

p307TROPONIN LEVELS AFTER SEIZURES AND RELA-TIONSHIP TO CARDIOVASCULAR RISK FACTORSA. Fawaz*, W. Nasreddine�, S. Atweh*, J. Wazneh*, A. Rabah*,M. Arabi*, and A. Beydoun**American Unveristy of Beirut, 2020, Lebanon; and �RaficHariri University Hospital, Beirut, Lebanon, Beirut, Lebanon

Purpose: Troponin is a very sensitive marker of cardiac injury. Conflict-ing data regarding elevation of troponin level following generalized tonicclonic seizures (GTCs) have been reported. In this study we hypothesizedthat troponin elevation after GTCs occurs more frequently in patientswith cardiovascular risk factors.

Method: Consecutive patients who presented to ER over a one year per-iod with a GTC and whose work up included troponin T level wereincluded. Patients with cardiac symptoms at the time of admission orrenal insufficiency were excluded. The frequency and risk factors for ele-vated troponin levels in this cohort were analyzed.

Result: Fourteen patients (mean age: 54 years; range: 19–87) wereincluded. Four patients (28.6%) had an elevated troponin level (Mean =0.06, range: 0.035–0.076). Those four patients were significantly olderthan those with normal levels (77.5 vs. 45.5 years, P = 0.035). EKGs inthese patients were normal. Of the eight patients 60 years or older, four(50%) had an elevated troponin level. The coronary heart disease score(CHD) was significantly higher in patients with high troponin comparedto those with normal troponin levels (13.5 vs. 9.75, P = 0.012).

Conclusion: Elevated troponin levels can occur after a GTC. The signif-icantly higher frequency in the elderly and in patients with high CHDscores strongly suggests that this increase is mostly due to cardiac injury.

p308OCCURRENCE OF ICTAL ARRHYTHMIA IS ASSOCI-ATED WITH A FIRST-DEGREE FAMILY HISTORY OFEPILEPSYG. O’ Connor, A. O’ Donnell, G. Mullins, E. Chaila, andN. DelantyBeaumont Hospital, Dublin, Ireland

Purpose: Seizure-induced disturbances in cardiac rhythm (known as ic-tal arrhythmias) are well recognised phenomena, the causes of which areunclear. To explore a possible genetic basis for this phenomenon, wesought to quantify the strength of association of ictal arrhythmia with afirst-degree family history of epilepsy.

Method: We identified all patients admitted to the Epilepsy MonitoringUnit in our centre between January 2005 and August 2011. For inclusion,patients had to have had definite epileptic events during the period ofmonitoring, and to have their details recorded on our epilepsy-specificelectronic patient record. For all patients included, we recorded demo-graphic details, family history of epilepsy, imaging findings and EEGfindings, and we recorded the occurrence or not of any ictal arrhythmia.For all the specified features, we calculated the significance of the associ-ation between them and the occurrence of ictal arrhythmia.

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Result: A total of 224 patients met the criteria for inclusion. Of these, 13patients (5.8%) had an ictal arrhythmia other than sinus tachycardia. Afirst-degree family history of epilepsy was found to be associated withthe occurrence of ictal arrhythmia (p = 0.0067). There was no statisticallysignificant association for any of the other features studied, includinghemisphere of seizure onset, extratemporal seizure focus or imaging find-ings.

Conclusion: The association of ictal arrhythmia with a first-degree fam-ily history of epilepsy has not been demonstrated previously, and sug-gests an underlying genetic basis for this phenomenon. Further researchinto the underlying genetic mechanism of ictal arrhythmia is warranted.

p309ASSOCIATION BETWEEN EPILEPSY AND CYSTICER-COSIS AND TOXOCARIASIS: A POPULATION-BASEDCASE–CONTROL STUDY IN AN URBAN SLUM ININDIAG. Singh, J. Bawa, D. Chinna, A. Chaudhary, K. Saggar,M. Modi, and J. W. SanderDayanand Medical College and Hospital, Ludhiana, India

Purpose: To study the association between epilepsy and exposure to theparasites, Toxocara canis and Taenia solium.

Method: A door-to-door community-based survey of epilepsy was car-ried out in an urban slum area with a population of 15,750. People withactive epilepsy were subjected to detailed epileptological assessments,sleep and awake EEGs and high-strength (1.5 Tesla) epilepsy protocolmagnetic resonance imaging. For every case, one age- and gender-matched control was selected from the same community. Serologicalevaluation was carried out for both cases and controls to detect antibodiesagainst T. canis and T. solium.

Result: The crude prevalence of active epilepsy was 7.2/1000. 114 peo-ple with confirmed active epilepsy (45 females; 69 males) and 114 con-trols were enrolled. The prevalence of antibodies to T. canis was similarin people with active epilepsy (4.4%, 5 of 114 people) and in controls(6.1%, 7 of 114 people). The prevalence of antibodies to T. solium was23.7% (27 out of 114 cases) in people with active epilepsy, which wassignificantly higher than the prevalence in controls (13 out of 114 cases;11.4%) (P = 0.02). After adjusting for potential confounding factors, con-ditional (fixed-effects) logistic regression provided an odds ratio of 2.55(95% CI, 1.14 to 6.28). Nineteen people with active epilepsy demon-strated evidence of neurocysticercosis on MRI, (solitary cysticercus gran-uloma – 7, solitary calcification – 7 and multiple mixed stages – 5).

Conclusion: Although significant association between T. solium expo-sure and epilepsy was observed but no such association was seen betweenT. canis and epilepsy.

p310ACUTE PURE RED CELL APLASIA. RARE COMPLICA-TION OF LAMOTRIGINE TREATMENTH. Ikeda, H. Ikeda, and Y. InoueNational Epilepsy Centre, Shizuoka Institute of Epilepsy andNeurological Disorders, Shizuoka, Japan

Purpose: To report that pure red cell aplasia (PRCA) can occur as a rareside effect of lamotrigine (LTG).

Method: We report a patient presenting with acute PRCA followingLTG treatment.

Result: Patient is a 25 year-old female with focal epilepsy and mentalretardation. She has a history of surgery for cerebellar tumor, subsequent

radiation therapy and chemotherapy at age 1 year. Her complex partialseizure started at age 19 years. She was treated with various medicationsincluding valproate (VPA) (as monotherapy for 1 year) without effectsnor relevant side effects. We gave her LTG up to 200 mg/day without sei-zure control. We added VPA 200 mg/day, then she became seizure free.Shortly after addition of VPA, normocytic normochromic anemiaemerged and rapidly progressed to reticulocyte count 0&. Leukocytope-nia and thrombocytopenia were not observed. Drug-induced acute PRCAwas suspected and VPA was discontinued, but anemia still progressed tohemoglobin (Hb) 5.7 g/ml. Transfusion of two units of packed red cellswas needed. As reticulocyte count still remained 1& on 20th day aftercessation of VPA, LTG was discontinued. Soon after discontinuation ofLTG, reticulocyte count increased dramatically up to 116&, and subse-quently anemia improved. Two months after discontinuation of LTG,RBC and Hb were normalized.

Conclusion: To our knowledge, this is the second case report of PRCAfollowing LTG treatment in a patient without known hematological dis-order. Monitoring blood count is highly recommended after initiation ofLTG treatment.

p311THE ROLE OF MINOCYCLINE ON DEVELOPMENT OFAMYGDALA KINDLING IN WISTAR RATSS. M. Beheshti Nasr, and M. Mohammad-ZadehSabzevar University of Medical Sciences, Sabzevar, Iran

Purpose: Minocycline is a derivative of tetracycline that has anti-inflammatory, antiappoptic and antioxidant properties. Minocyclinereadily crosses the blood brain barrier and attenuates inflammation, italso affect on neural cell activity. For example it has been shown minocy-cline inhibit microglia activation and reduce astrocytic reactivation addi-tion it has neuroprotective effects. As far as there is interaction betweencell death and seizure, the aim of this study is examination of the role ofminocycline on amygdala kindled seizures in rat.

Method: In this experimental study, three group animals (21 rats), aftersterotaxic surgery and 1 week recovery period, rats received kindlingstimulations (twice daily at 6 hour interval). Group 1(n = 7) animalsreceived daily kindling stimulations. Group 2 (n = 7) and 3(n = 7) 60 minbefore kindling stimulation received saline (1 ml/kg) and minocycline(25 mg/kg) respectively.

Cumulative Afterdischarge duration (ADD), Cumulative Seizure dura-tion (SD) and Seizure Stage (SS) were recorded and compared relative tocontrol group. Data analyzed with Statistica software (Ver 5.5). Repeatedmeasure ANOVA and Post hoc tukey test for comparison within groupsand student's t-test was used for comparing two groups of data. A P-valueof less than 0.05 was considered to represent a significant difference.

Result: In group 3 intraperitoneal administration of minocycline for 10days reduced cumulative ADD [F(18, 216)=3.5, p < 0.001]¡ and cumula-tive SD [F(19, 228)=3.8, p < 0.001] significantly relative to control group(group 2). It also significantly increased the mean number of stimulationsto achieve to seizure stages of 3 (P < 0.05), and 5 (P < 0.001).

Conclusion: According to obtained results it may be concluded thatapplication of minocycline have anticonvulsant effect on kindling modelof epilepsy.

p312DIFFERENT TYPES OF HEADACHE IN PATIENTSWITH EPILEPSY – CLINICAL INVESTIGATIONSC. Lorenzen, M. Prieschl, M. Bergmann, G. Walser, C. Gneis,I. Unterberger, and G. LuefMedical University Innsbruck, Innsbruck, Austria

Purpose: Epilepsy is known to be associated with different comorbidi-ties in particular headache. The aim of our study was to examine the

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distribution of different headache types in patients with epilepsy. Wetried to determine whether migraine is the most common headache typein epilepsy and if antiepileptic drugs are useful for headache prophylaxis.

Method: In this single-centre study we consecutively investigatedpatients with epilepsy using a validated self-administered headache ques-tionnaire for screening for migraine (MIG), tension-type headache(TTH), and trigeminal-autonomic cephalgias (TAC). Additionally weasked for onset and type of epilepsy, seizure associated headache, anti-epileptic drug treatment and their influence on headache followed by aquestion regarding seizure frequency.

Result: Five hundred epileptic patients with equivalent sex distributionand a mean age of 45.52 years (+-17,26) were enrolled. One hundredsixty three patients, 43.2% female and 22.0% male, reported to sufferfrom headache. Migraine was the most frequent type in general (41.7%),and in women (47,2%), TTH in male (41,8%). Antiepileptic drug treat-ment was used by 158 patients, sixty (38.0%) reported to have a reductionin frequency of headache. With regard to the different headache types,levetiracetam reduced frequency of headache best (50.0%), followed byvalproic acid (41.2%) and lamotigine (26,3%).

Conclusion: Three different headache types are present in epilepsypatients. A short questionnaire seems to be helpful in diagnosing head-ache. AED treatment improved headache and polypharmacy. Levetirace-tam followed by Valproat was shown to have the best influence onheadaches in general.


p313PSYCHOSOCIAL OUTCOME AND PATIENT SATIS-FACTION 10 YEARS AFTER TEMPORAL LOBE RESEC-TION FOR EPILEPSYL. Andersson-Roswall, E. Engman, H. Samuelsson, andK. MalmgrenInstitute of Neuroscience and Physiology, Gothenburg, Sweden

Purpose: Knowledge about long-term psychosocial outcome of tempo-ral lobe resection (TLR) for epilepsy is limited. The aim of this study wasto explore long-term psychosocial outcomes and patient satisfaction withTLR and to investigate the relationship between long-term vocationaland memory outcomes.

Method: A cohort of 51 patients was prospectively followed 10 yearsafter TLR. Psychosocial and neuropsychological data was prospectivelyascertained at baseline and 10 years after surgery and at correspondingtime-points for 23 controls. 40/51 patients (78%) also answered two sur-veys at long-term follow-up including the Hospital Anxiety and Depres-sion Scale (HAD), a global quality of life (QOL) assessment andquestions on patient satisfaction with surgery.

Result: Fewer patients worked 10 years postoperatively (TLR: 61%;controls: 96%; p = 0.002) compared to baseline (TLR: 73%; controls:83%; NS). The odds of working full time 10 years after surgery were 9.5times higher with seizure freedom (p = 0.022). There were no associa-tions between working at 10 years and side of resection and verbal mem-ory outcome. Most patients scored low on HAD indicating few emotionalproblems. Seizure-free patients were more satisfied with surgery (p =0.027), experienced less disadvantages of their TLR (p = 0.022), and hada better QOL (p = 0.014).

Conclusions: In this study TLR did not lead to better vocational out-come. However, seizure-free patients were more likely to work full-time10 years postoperatively and verbal memory impairment did not have aninfluence on vocational outcome. Patients were in general satisfied withepilepsy surgery, those seizure-free more than those with seizures.

p314A COMPARISON STUDY OF THE QUALITY OF LIFE(QOL) IN EPILEPSY, MS, AND HEALTHY CONTROLSIN SAUDI ARABIAH. Alkhamees, and C. SelaiUCL, London, UK

Purpose: This study was conducted to compare (QOL) in patients withepilepsy, patients with MS and healthy controls from Saudi population.

Method: The QOL of (110) patients with epilepsy, (114) patients withMS, and (136) healthy controls all from Saudi Arabia was assessed usingtwo scales (QOLIE-31 and the RAND SF-36). Translation and validationof the QOLI-31 from English to Arabic was done.

Result: A comparison between the three groups QOL will be presentedas preliminary results.

Conclusion: Preliminary results show the QOL within the three groups.

p315EPILEPTIC ENCEPHALOPATHIES OF THE LANDAU-KLEFFNER AND CONTINUOUS SPIKE AND WAVESDURING SLOW-WAVE SLEEP TYPES: GENOMIC DIS-SECTION MAKES THE LINK WITH AUTISMG. Lesca*, G. Rudolf�, A. Labalme�, E. Hirsch�,A. Arzimanoglou*, P. Genton§, J. Motte–, A. De Saint Martin**,M. Valenti**, C. Boulay**, J. De Bellescize��, P. Keo-Kosal��,N. Boutry-Kryza��, P. Edery*, D. Sanlaville*, andP. Szepetowski§§

*CRNL, CNRS UMR 5292, INSERM U1028, Lyon, France;�Strasbourg University Hospital, Strasbourg, France;�University Hospital of Lyon, Bron, France; §Henri GastautHospital, Marseille; –American Memorial Hospital, ReimsUniversity Hospital, Reims, France; **Strasbourg UniversityHospital, Strasbourg; ��Epilepsy, Sleep and PediatricNeurophysiology Dpt, Lyon, France; ��Lyon UniversityHospital, Claude Bernar University Lyon 1, Lyon; and§§Mediterranean Institute of Neurobiology (INMED), Marseille,

Purpose: The continuous spike and waves during slow-wave sleep syn-drome (CSWSS) and the Landau-Kleffner (LKS) syndrome are two rareepileptic encephalopathies sharing common clinical features includingseizures and regression. Both CSWSS and LKS can be associated withthe EEG pattern of electrical status epilepticus during slow-wave sleepand are part of a clinical continuum that at its benign end includes Rolan-dic epilepsy (RE) with centro-temporal spikes. Patients can also havebehavioral manifestations that overlap the spectrum of autism disorders(ASD). An impairment of brain development with complex interplaybetween genetic and non-genetic factors has been suspected but the path-ophysiology of CSWSS and of LKS remains unknown. In the recentyears, the participation of rare copy number variations (CNVs) in the sus-ceptibility to various brain diseases including epileptic and autistic disor-ders has been demonstrated.

Method: The involvement of rare CNVs in 61 CSWSS and LKS patientswas questioned using comparative genomic hybridization assays (4 ·180 Agilent microarrays).

Result: Whereas the patients showed highly heterogeneous in genomicarchitecture, several potentially pathogenic alterations were detected.Many of these corresponded to genomic regions or genes that have beenassociated with either ASD, or speech or language impairment, or RE.Particularly, CNVs encoding cell adhesion proteins were detected withhigh frequency.

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Conclusion: Overall our data bring the first insights into the possiblemolecular pathophysiology of CSWSS and LKS. The detection of celladhesion genes and the strong overlap with the genetic and genomic ASDnetworks, provide an exciting and unifying view on the clinical linksbetween CSWSS, LKS and ASD.

p316SEIZURE SEMIOLOGY OF A HOT WATER SEIZURECASEO. Karadas*, I. Ipekdal�, and H. L. Gul�

*Erzincan Military Hospital, Erzincan, Turkey; �MarasalCakmak Hospital, Erzurum, Turkey; and �Kartal Education andResearch Hospital, Istanbul, Turkey

Purpose: Hot water epilepsy (HWE) or bathing epilepsy is the group ofreflex epilepsies. It is induced by hot water pouring over the head, face,neck, or trunk during bathing. The aim of this study was to demonstratethe seizure semiology by following up the seizure with all the changesthat occured before, during and after the seizure.

Method: An informed consent form was signed by the patient and theneeded precautions were taken. Under the supervision of a doctor and anurse; the patient's seizure was induced by having a bath with 40�C hotwater. Each step of the semiology was recorded by a neurologist.

Result: 1,5 minutes after starting to bath, the patient's breathing becamedeeper and a fearful facial expression had developed. This status had con-tinued for 5–10 seconds, then a pause in the speech and pupillary dilata-tion was detected. 5 seconds after this status, the patient becameunconscious with oral automatisms and the deviation of the head and eyesto the right. At this state, intervention was made and while taking thepatient out of the bath, he had a 6–8 seconds of generalised tonic seizurefollowed by a 20 seconds of generalised clonic seizure. His postictal con-fusion continued for 10 minutes and after that period, his neurologicalexamination had turned to normal.

Conclusion: This case is important for; the determination of the seizuresemiology of hot water epilepsy as a reflex epilepsy and the comparisonof hot water epilepsy with the other epilepsies.

p317DEREALIZATION DISORDERS IN EPILEPSYP. Vlasov*, and A. Chervyakov�

*Moscow State Medical and Stomatology University, Moscow,Russian Federation; and �Research Center of Neurology RAMS,Moscow, Russian Federation

Purpose: To examine the clinical and diagnostic value of derealizationdisorders in epilepsy. Deja vu (DV) phenomenon is the most commonand recognizable derealization disorder.

Method: Study group of 166 persons (average age 25,2 € 9,2; 63,2% ofwomen). Derealization was compared in two groups: I – healthy people(n = 139), II – patients with epilepsy (n = 27). Provided that healthyrespondents have never had any of the paroxysmal manifestations. Long-time EEG monitoring was performed for all patients of the second groupand for 5 healthy participants with frequent DV. We used our own uniquequestionnaire.

Result: For patients with epilepsy DV phenomenon occurs in crypto-genic and symptomatic focal epilepsy, it can be combined with virtuallyall types of seizures, could be aura of a seizure, and self-attack. For thefirst time there was recorded EEG-pattern of DV phenomenon in epi-lepsy, that is characterized by the beginning of spike activity in the righttemporal lobe and, in some cases (longer duration of phenomenon),ended in slow wave, theta-delta activity in the right hemisphere. Inone healthy volunteer the EEG-pattern of DV-phenomenon was

characterized by desynchronization of basic EEG-rhythm. The mostimportant diagnostic criteria for epileptic patients are dynamic character-istics of the DV: elongation, increased appearance of negative emotions.

Conclusion: There was allocated of two types of deja-vu: ‘‘pathologi-cal-epileptic’’, characteristic of patients with epilepsy and equivalent toan epileptic seizure, ‘‘nonpathological-nonepileptic’’ deja-vu, which ischaracterized for healthy people.

p318TRANSIENT EPILEPTIC AMNESIA: DESCRIPTION OFTWO CASESS. Meregalli, and M. BrioschiA. O. Niguarda C Granda, Milano, Italy

Purpose: Case reports over the past 100 years have raised the possibilitythat epilepsy can manifest itself in episodes of amnesia. Transient Epilep-tic Amnesia (TEA) is a relatively recently characterized syndrome oftemporal lobe epilepsy.

Method: Transient Epileptic Amnesia (TEA) is a distinctive syndromeof temporal lobe epilepsy principally affecting middle-aged people, giv-ing rise to recurrent, brief attacks of amnesia, often occurring on waking.It is associated with a form of persistent interictal memory impairment,i.e. accelerated long-term forgetting and remote memory impairment.The syndrome is of clinical importance, as the amnesic episodes are oftenmisdiagnosed initially but respond promptly to antiepileptic drugs. Thediagnostic criteria for TEA are as follows: 1) A history of recurrent wit-nessed episodes of transient amnesia. 2) Cognitive functions other thanmemory judged to be intact during typical episodes by reliable witness 3)Evidence for a diagnosis of epilepsy based on one or more of the follow-ing: (a) epileptiform abnormalities on electroencephalography (b) theconcurrent onset of other clinical features of epilepsy (c) a clear-cutresponse to antiepileptc drugs. We describe two new cases of TEA, fillingthese diagnostic criteria.

Result: WE describe two middle-aged womans, with episodes of TEA,promptly responding to antiepileptic drugs-therapy.

Conclusion: Transient Epileptic Amnesia is an under-recognized buttreatable cause of transient memory impairment. It is important to make adifferential diagnosis with other forms of transient impairment of mem-ory, like Transient Global Amnesia etc.

p319EPILEPTC APHASIA: A DESCRIPTION OF 10 NEWCASESA. L�pez-Ferreiro*, X. Rodr�guez-Osorio*, J. C. Fern�ndez-Ferro�, T. Garc�a-Sobrino*, M. Rodr�guez-YaÇez*, M. Arias*,J. Pardo*, E. Corredera*, and F. J. L�pez-Gonz�lez**Complejo Hospital Cl�nico Universitario de Santiago deCompostela, Santiago de Compostela, Spain; and �HospitalInfanta Elena, Madrid

Purpose: Recurrent or prolonged aphasia as sole clinical manifestationof epilepsy is a rarely described phenomenon. We aim to describe the epi-leptic aphasias diagnosed in our hospital.

Method: We considered ictal aphasia as language production with apha-sic features in conscious patients. Episodes were classified as status epi-lepticus or simple partial seizures according to ILAE guidelines, and maypresent as Broca, Wernicke or mixed aphasia. Diagnosis was based onclinical features plus EEG findings or clear response to antiepilepticdrugs (AED), with exclusion of acute structural aetiologies on MRI. We

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analyzed demographic, clinical and EEG characteristics, response totreatment and follow-up.

Result: Ten women (100%), with a mean age of 66.6 years old wereincluded (49–85) Two had previous history of epilepsy. Mixed aphasiaoccurred in 5 patients, Broca in four and Wernicke in one. In 9 cases anictal EEG was obtained: 4 demonstrated left regional epileptiform activ-ity and other 4, left hemisphere slowing. Six patients presented with sta-tus epilepticus and four with simple partial seizures. One patient showedtransitory edema in the MRI. Benzodiazepines were used as first-lineAED in 6 patients, with clinical response in 4, EEG response in 1 andboth in 1. All patients clinically recovered with AEDs (LEV 70%). In thefollow-up, 7 cases achieved an excellent control and three recurred.

Conclusion: Diagnosis of epileptic aphasia is challenging. An epilepticaetiology should be considered in the differential diagnosis of episodicspeech errors. Ictal EEG findings and response to AEDs are useful in thediagnosis and management of these patients.

p320SEMIOLOGIC AND EEG FEATURES OF PATIENTSWITH TEMPORAL LOBE EPILEPSY AND HIPPOCAM-PAL SCLEROSIS WHO WERE SEIZURE-FREE FOL-LOWING SURGERYH. Ertasoglu Toydemir*, C. �zkara�, and M. Uzan�

*Sisli Etfal Research and Education Hospital, Istanbul, Turkey;�Istanbul University School of Medicine, Istanbul, Turkey; and�_Istanbul University Cerrahpasa Medical Faculty, Istanbul,Turkey

Purpose: Despite the high rate of favorable outcome after standardizedsurgery, 20–30% of patients with mesial temporal lobe epilepsy and hip-pocampal sclerosis (MTLE-HS) still continue to experience seizures.The aim of this study is to determine whether there is evident semiologicand EEG features which may predict the seizure freedom after surgery.

Method: Semiologic and EEG findings of 126 ictal video-EEG record-ings corresponding to 50 patients who stayed seizure free for at least 3years (mean: 9.46 € 3.20; range: 3–14.5 years) after surgery werereviewed. About 94% of them have already discontinued drugs.

Result: Aura was reported in 82% (n:41) of the patients. Epigastric sen-sation was the most common aura. Early symptoms (within the first 30seconds) were contralateral arm dystonia (%60), ipsilateral hand automa-tisms (%54) and oro-alimentary automatisms (%48). Two or three ofthese symptoms were seen together in %56 of the patients without anyunique sequence. Ictal EEG findings revealed localized and lateralizedactivity in 66% of them.

Conclusion: The presence of three semiological features during the earlyictal period and localized and lateralized ictal EEG activity seem to becommon features in this highly selected patient population. Although,other types of semiologic and EEG findings detected besides them suggesta more extended epileptogenic zone, the fact that they benefit from thesame surgical procedure may be associated with the critical role of resectedarea in both the generation and propagation of the seizure activity.

p321CHARACTERISTIC SEIZURE SEMIOLOGY INPCDH19-RELATED INFANTILE EPILEPTIC ENCEPHA-LOPATHYH. Ikeda, K. Imai, H. Ikeda, R. Takayama, H. Ohtani,H. Shigematsu, Y. Takahashi, and Y. InoueNational Epilepsy Center, Shizuoka Institute of Epilepsy andNeurological Disorders, Shizuoka, Japan

Purpose: To elucidate features of the seizure semiology in children withprotocadherin 19-related epileptic encephalopathy (PCDH19EE),because of lack of detailed description regarding seizure manifestationbased on video-EEG recordings in the literature.

Method: We analyzed ictal video-EEG recordings of 26 seizures inthree girls with PCDH19EE.

Result: The sequence of seizure manifestation was very similaramong all three patients, consisting of five common segments, whichwe named ‘‘Jerk’’, ‘‘Reactive’’, ‘‘Mild tonic’’, ‘‘Fluttering’’ and‘‘Post-ictal/Oral automatism’’. Some segments are brief or lacking,while others are long or pronounced. ‘‘Reactive’’, ‘‘Mild tonic’’ and‘‘Fluttering’’ segments are more characteristic. In ‘‘Reactive’’, thepatients seemed so startled by sudden ‘‘Jerk’’ that they reactivelyturned over. Tonicity in ‘‘Mild tonic’’ was less intense than that oftonic-clonic seizures of other epilepsies. ‘‘Fluttering’’ was character-ized initially by asymmetric, less rhythmic, less synchronous tremu-lous movement and later by subtle clonic movement. There wassubtle oral automatism in the postictal phase. Seizure lasted from afew to sixty seconds. All seizures occurred in clusters associatedwith high fever. Ictal EEGs started initially bilateral in some, butasymmetric at the very onset in some others, and later showedapparent asymmetric rhythmic discharges.

Conclusion: Seizures have more or less asymmetric focal features in theelectro-clinical aspects. Characteristic seizure sequence in PCDH19EEwas so unique that its occurrence in clusters associated with high fever ingirls would readily suggest PCDH19EE.


p322RELIABILITY OF POSTICTAL NOSE RUBBING FORLOCALIZATION AND LATERALIZATION OF EPILEP-TOGENIC ZONE IN FOCAL EPILEPSIESN. M. Vojvodic*, A. J. Ristic*, L. M. Popovic�, V. L. Bascarevic�,D. V. Sokic*, A. Parojcic*, S. M. Jankovic*, M. M. Kovacevic*,L. Brajkovic§, and B. Djurovic�

*Neurology Clinic, Belgrade, Serbia; �St Sava Hospital,Belgrade, Serbia; �Clinic of Neurosurgery, Clinical Center ofSerbia, University of Belgrade, School of Medicine, Belgrade,Serbia; and §Institute of Nuclear Medicine, Belgrade, Serbia

Purpose: To evaluate the usefulness of postical nose rubbing (PNR) asthe localization and lateralization sign in focal farmacoresistant epilep-sies.

Method: Retrospectively, we analyzed seizure semiology in 266patients with focal farmacoresistant epilepsy. All patients wereundergone five day noninvasive video-EEG monitoring in our telem-etry unit and brain MRI according to the presurgical protocol. In162 patients we were able to establish the lobar diagnosis. In allpatients we analyzed clinical seizure semiology in order to determinethe occurrence of PNR in temporal lobe epilepsies (TLE) vs. extra-temporal lobe epilepsies (ETLE), and it's lateralizing value (ipislater-al or contralateral to the epileptogenic zone) when performexclusively with one hand.

Result: We found PNR in 40 out of 106 patients with TLE and in 7 outof 56 patients with ETLE (37,7% vs. 12,5%, p = 0.001). In 27 (57,4%)patients, PNR was performed always with hand ipsilateral to the epilepto-genic zone, in 11 (23,4%) patients with contralateral hand and in 9(5,2%) patients with both hands (p = 0.008).

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Conclusion: We found PNR was reliable localizing sign for TLE andwhen performed exclusively with one hand, it was significantly morecommon with ipsilateral hand to the epileptogenic zone.

Basic Science 5Tuesday, 02 October 2012

p323THE OUTCOME OF THERAPIES IN REFRACTORYAND SUPER-REFRACTORY CONVULSIVE STATUS EP-ILEPTICUS AND RECOMMENDATIONS FOR THER-APYM. Ferlisi, and S. ShorvonNational Hospital for Neurology & Neurosurgery, London, UK

Purpose: The purpose of this report is to provide a comprehensive anal-ysis and synthesis, from the published literature from 1981, of the out-come of therapies used in refractory or super-refractory statusepilepticus, and to provide recommendations about a treatment protocol.

Method: We analysed all 141 papers reporting outcome of 1168 patientswith refractory and super-refractory status epilepticus, treated with vari-ous therapies.

Result: Control of refractory and super-refractory status epilepticus wasreported in 74% of the cases treated with anaesthetics – 64% for barbitu-rate, 78% for midazolam and 68% for propofol. Variable rates of controlwere achieved for other therapies – including other anaesthetics, antiepi-leptics, the use of hypothermia, immunotherapy, the ketogenic diet, mag-nesium, pyridoxine, immunotherapy, electroconvulsive therapy (ECT),cerebrospinal fluid (CFS) drainage, VNS and emergency resective sur-gery. The reported mortality rate of this stage of status epilepticus was35% and a further 13% of patients were left with severe neurological def-icit.

Conclusion: There is a remarkable dearth of information about the out-come of the various therapies used, often widely so, to control refractoryor super-refractory status epilepticus despite its high mortality and mor-bidity. There are no controlled studies, and information is based almostentirely on open, often small and retrospective, case series or casereports. Based on our findings, we make recommendations about firstand second line therapy, and suggest a protocol of therapy. We alsoemphasis the need for an international case registry to provide betterquality outcome information.


p324EEG AND MRI FINDINGS IN SUPER REFRACTORYSTATUS EPILEPTICUS DUE TO UNKNOWN UNDERLY-ING ETIOLOGYA. Ferrari, P. Renzetti, M. Ferretti, F. Piccardo, N. Mavilio, andG. A. OttonelloIRCSS A.O.U San Martino, Genova, Italy

Purpose: Super Refractory Status Epilepticus is a stage of RefractoryStatus Epilpticus and it is characterized by unresponsiveness to initialanesthetic therapy. It is defined as a condition that continues or recurs 24hours or more after the onset of anesthesia.

Method: We report the case of 40-years-old man affected by cerebellaratrophy who suffered myoclonic seizures with onset at 3 years old. He

has been seizure-free for a long period since he developed Status Epilep-ticus followed by Refractory SE, than Super Refractory SE occurred.EEG and MRI changes occurred during his follow-up: serial MRI exam-inations showed progressive cortical laminar necrosis while EEG record-ings showed paroxysmal epileptiform discharges. Suppression burstnever appeared after anesthetic therapy. These findings suggest an ongo-ing neuronal injury that currently persists after 5 months of SE despite alltreatments.

Result: These findings suggest an ongoing neuronal injury that currentlypersists after 5 months of SE despite all treatments.

Conclusion: Morbidity and mortality in Super Refractory SE is veryhigh. The outcome depends on the underlying etiology but, in our patient,no cause was found until now.

p325EPILEPTIC STATUS IN ADULTSD. Ndoja, N. Bendo, A. Seferi, A. Kuqo, and Z. NdroqiUHC, Tirana, Albania

Purpose: Electro-clinical-etiological finding of SE.

Method: We studied 28 patients hospitalized in ICU (17 F, 11 M withmedian of 46 years old), from 2008 to 2010, with mean SE duration of 2hours.

Result: SE prevalence had 2 picques; in adolescentes-younger adults(10), and in older(10). All displayed generalized GSE: 11 primaryPGSE, 17 secondary SGSE (Shorvon 1983). Among PGSE : 9 hadconvulsive, myoclonic, atonic SE in 2. In SGSE; 14 had PMS onset:hemy without, with Jaksonian march (4,2) superior 5; whereas versiveand CPS onset (3,3). Etiology of PGSE; IgE in 7, metabolic in 3,eclampsy in one. Triggeref factors were AEDs changes, fever and al-col. In SGSE: vascular origin in 7, trauma 3, Tu 4, non-lesional 2, hyg-roma, FCD dementia in 1 respectilvely. EEG post-SE: diffuse/ bilateralin 8, lateralized 7; ictal with partial onset in 2; not available 7; normalin 3 patients. Two pt died, while BZD and PHT in refractory casesprovided the good outcome, in others.

Conclusion: SGSE prevailed more than PGSE. In PGSE, IGE weremore frequent than metabolic SE. in SGSE the vascular etiology wasmore frequent than trauma and Tu, then than DA, MCD, and non-lesion-al. EEG : diffuse/ bilateral more than lateralized, normal finding.

p326A CASE OF SEVERE FORM OF PANDAS-LIKE COURSEL. C. Heberle*, D. Neubauer�, A. Altawari*, and N. Alothman**Al Sabah Hospital, Kuwait, Kuwait; and �University Children'sHospital Ljubljana, Ljubljana, Slovenia

Purpose: Pediatric Autoimmune Neuropsychiatric Disorder Associatedwith Streptococcal infections (PANDAS) presents as a spectrum of post-infectious neurological disease that extends well beyond Syndenhamchorea and includes different neuropsychiatric conditions including com-plex tic disorders and obsessive-compulsive behavior.

Method: We describe a boy with an extremely severe and life-threaten-ing course who responded well to immunotherapy but is left with residualepilepsy and depression.

Result: K. was 11-year old boy who had had tics one year before admis-sion due to low grade fever, throat infection and progressive lethargywith absence like attacks followed by epileptic status and apneas. After

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institution of anticonvulsive treatment and antibiotics seizures subsidedand a full-blown clinical picture emerged with very frequent complextics, fidgety and psychiatric behavior to be soon followed by another per-iod of status epilepticus and apneas necessitating intubation and intensivecare. Results showed very high titers of ASOT (3200 IU/ml), MRI brainfaint thalamic changes, CSF study was normal. EEG showed progressiveslowing of background activity which later normalized. Despite no epi-leptiform discharges he had occasional focal seizures. With penicillinprophylaxis, combined treatment with immunoglobulins and methyl-prednisolone the child gradually improved, however he still has occa-sional epileptic seizures, tics and depressive behavior. His recent mini-mental test proved normal result.

Conclusion: We believe that this boy had s severe form of PANDAS-like condition, presenting also as epileptic statuses, finaly leading toresidual epilepsy and depressive behaviour.

p327EFFICACY OF INTRAVENOUS LACOSAMIDE INSYMPTOMATIC FOCAL MOTOR STATUS EPILEPTI-CUS: A CLINICAL AND VIDEO-POLYGRAPHIC STUDYM. Trivisano, G. D’Orsi, M. G. Pascarella, F. Pacillo,M. Ferrara, E. Carapelle, C. Luisi, M. T. Di Claudio, andL. M. SpecchioEpilepsy Center – Clinic of Nervous System Diseases, Universityof Foggia, Riuniti Hospital, Foggia, Italy

Purpose: To evaluate efficacy and tolerability of intravenous lacosa-mide (LCM) in the treatment of Non-Convulsive Status Epilepticus(NCSE) after failure of conventional therapy.

Method: Patients presented with refractory NCSE underwent LCM i.v.therapy and a long-term video-EEG/polygraphic monitoring before andafter LCM treatment.

Result: Three patients (2 female, 1 male), aged between 60 and 70,with symptomatic (gliomatosis cerebri, brain metastasis of lung adeno-carcinoma, ischemic stroke) focal motor status epilepticus were investi-gated. The first patient showed left fronto-central polyspike-and-waveactivities associated with tonic contraction of right orbicularis oris fol-lowed by tonic-clonic activity in the right masseter and orbicularis oris,hypersalivation and aphasia. The second one presented with aphasia andtonic-clonic activity of right extensor hand muscles associated with leftfronto-temporal epileptic discharge. The third one had repetitive left legtonic-clonic activity with epileptic discharge over the vertex and rightanterior region. All patients achieved a clinical and polygraphic disap-pearance of the focal motor status within 24 hours since the first admin-istration of 400 mg of LCM i.v. after an ineffective treatment with DZP(10 mg i.v.) and LEV (3000 mg i.v.). In all patients the treatment withPHT was not possible because of hypotension in two and sinus brady-cardia in one. All patients did not have any seizures with a maintainingdose of 400 mg/day.

Conclusion: Our clinical and polygraphic study suggest that LCM i.v.may be effective in the treatment of refractory focal motor NCSE, but lar-ger studies are needed to confirm the efficacy of LCM in the treatment ofthis type of NCSE.

p328CONVULSIVE STATUS EPILEPTICUS IN CHILDREN-PREDICTORS OF OUTCOMEN. Tatishvili, and T. ShatirishviliCentral Children Hospital, Tbilisi, Georgia

Purpose: Convulsive Status Epilepticus (CSE) is one of the most com-mon neurological emergencies in children with high mortality and mor-bidity. Prognostic value of risk factors as age, etiology, duration, qualityof pre hospital treatment is not well studied. Purpose- to study correlationof duration, etiology and type of status on outcome. Also Effect of qualityof pre hospital treatment on short term outcome.

Method: Hospital based study. Children admitted to Central ChildrenHospital with CSE from 01.01.09 till 31.12.10 were evaluated and moni-tored for at least 12 months.

Result: Among 870 hospital admissions, were 46 cases of CSE (5.3%).Average age was 4.9 years. In 5 cases status was first manifestation ofepilepsy. 20 patients had previous history of epilepsy, 9 were on AED. 5had drug resistant epilepsies. 12 patients had developmental delay. Statuswas focal in 24 and generalized in 22 cases. In 8 cases CSE was febrile,infections of CNS in 7 cases. Stroke was manifested with CSE in 3 cases(2 ischemic, one hemorrhagic) . Duration of CSE varied from 30–180min. mean 50.5. Mortality rate was 4.3% (2 patients). Data revealed poorpre hospital care – over treatment with BZD. All patients received 1–2doses of BZD, 14 patients 3 or 4 doses.

Conclusion: Analysis of data showed no correlation of outcome withage, type of epilepsy, duration of status. There was negative correlationbetween prehospital care and outcome. Patients receiving 3–4 doses ofBZD at prehospital level had longer stay on ventilation and worst shortterm outcome (p < 0.001).

p329UTILITY OF ONE HOUR PORTABLE EEG RECORDINGIN DETECTION AND MANAGEMENT OF NON-CON-VULSIVE STATUS EPILEPTICUS IN PATIENTS WITHALTERED SENSORIUM IN A RURAL-BASED ICU INRESOURCE LIMITED SETTINGSS. D. Desai, P. B. Shah, B. S. Vaishnnav, D. S. Desai, S. Sheth,and J. MannariPramukhswami Medical College and Shree Krishna Hospital,Anand, Gujarat, India

Purpose: To identify the prevalence of non-convulsive status epilepti-cus [NCSE] in patients with altered sensorium in a rural based medicalintensive care unit [ICU] using one hour portable Electroencephalogra-phy [EEG] record and to assess its utility/ impact by assessing the numberof patients in whom treatment decisions changed after the portable EEGrecord.

Method: 70 adult patients admitted in medical ICU with altered senso-rium underwent one hour EEG for assessing presence of NCSE using pre-set defined clinical and EEG criteria. We assessed the relationshipbetween demographic characteristics, clinical features and the presenceof NCSE. We also assessed the number of patients in whom EEG record-ing lead to change in treatment by addition/ change/modification/stop-ping of anti-epileptic drug [AED] therapy and assessed its relationship tooverall patient outcome.

Result: NCSE was present in 13(18.57%) of our cohort of 70 patients.The common aetiologies for altered sensorium were metabolic encepha-lopathy (52.94%), intracranial infections (17.64%) and stroke(5.84%).Treatment was changed in 16 patients (22.85%) after EEG recording, ofwhom 11(68.75%) had NCSE and required addition of AED. Afterchanging treatment clinical improvement occurred in 7 patients(43.75%).

Conclusion: Our pilot study shows that one hour portable EEG inresource limited settings can identify NCSE in significant number ofpatients with altered sensorium in medical ICU and lead to treatmentchange and better outcome.

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p330ATYPICAL ABSENCE NONCONVULSIVE STATUS EPI-LEPTICUS IN CHILDREN WITH MEDULLOBLAS-TOMA AFTER CRANIOSPINAL IRRADIATION; APOSSIBLE LENNOX-GASTAUT SYNDROME MIMICK-ING ENTITYI. Maestro Saiz, A. B. Anaya-Chen, J. M. Prats ViÇas, A. IglesiasMartinez, B. Mateos, L. Perez, and I. YurrebasoCruces University Hospital, Barakaldo, Spain

Purpose: We describe three cases of pediatric-aged patients diagnosedof medulloblastoma who presented atypical absence nonconvulsive sta-tus epilepticus probably related to radiotherapy.

Method: Three children; 10 year-old-boy, 11 year-old-girl and 11 year-old-boy, previously diagnosed of medulloblastoma with completeresponse to treatment after chemotherapy and craniospinal irradiationwho presented tonic or generalized tonic-clonic seizures in the course ofthe disease, were admitted in our institution with the clinical suspicion oftumor-recurrence after presenting acute impairment of mental status.Patients underwent various diagnostic techniques such as structural MRI,lumbar puncture, blood and cerebrospinal fluid (CSF) cultures and video-electroencephalographic (EEG) recording.

Result: In all three patients, diagnostic structural MRI did not show anysignificant change comparing with previous exams and other tests dis-carded tumor recurrence. Video-EEG showed continuous generalizedslow spike-wave complexes in all children with no clinical changes ofbasal state during the recording. Three patients were diagnosed of atypi-cal absence nonconvulsive status epilepticus and were treated with LEVin two cases and with VPA in the other one, with complete remission ofsymptoms and epileptiform activity.

Conclusion: Despite medulloblastomas are tumors arising from cerebel-lum, epileptic seizures are common in the course of the disease, probablyrelated with radiotherapy which is an essential component in postopera-tive management. Atypical absence nonconvulsive status epilepticus isan unexpected late sequel that must be suspected, probably also relatedwith cerebrospinal radiation, classically also considered as one of the eti-ologies of Lennox-Gastaut syndrome. Early suspicion, diagnosis andtreatment of this entity, could prevent secondary morbidity and mortalityin these oncologic patients.

p331NON-CONVULSIVE STATUS EPILEPTICUS: PROFILEOF PATIENTS ADMITED ON A TERTIARY HOSPITALM. J. Aguilar Amat PriorHospital Universitario La Paz, Madrid, Spain

Purpose: Description of patients with non-convulsive status epilepticus(NCSE). To assess factors associated with mortality, complications andtreatment.

Method: Retrospective observational study of patients admitted forNCSE between 2008–2010. We analyzed demographic data, history ofepilepsy, treatment, type NCSE and variables associated with mortalityand complications.

Result: 30 patients (60% M). Mean age 62 years. Previous epilepsy :85% and 15% generalized. 70% symptomatic.

17 patients had focal complex NCSE, 7 and 6 simple focal SENC sta-tus of absence. 15% caused by changes in medication.

46.7% had complications (64% respiratory) and 6 patients died.No significant differences in complications and mortality in age, sex,

type, etiology and treatment of epilepsy, or type of NCSE. 70% ofpatients admitted to ICU (due to impairment on level of consciousness

and/or prolonged refractory status) had complications compared with30% of those not admitted to ICU (p < 0.05).

Of 17 previously treated patients, 10 were monotherapy, 7 polythera-py. 29.4% 1st generation drugs, 41.2% 2nd and 29.4% both.

Prior untreated patients: 85.7% initiated monotherapy (100% 1st gen-eration). Of those treated 33.3% increased number of drugs, decreased6%. The most widely used drug was valproic acid monotherapy (on 50%,high 40%) and levetiracetam in combination (on 100% high 81%).

Conclusion: Focal complexwas the most frequent NCSE. There weremore complications in patients with altered level of consciousness andrefractory status.

p332EFFICACY OF DIFFERENT THERAPEUTIC AGENTSIN STATUS EPILEPTICUSJ. Rçsche, K. Rantsch, U. Walter, and R. BeneckeUniversittsmedizin Rostock, Rostock, Germany

Purpose: We evaluated the efficacy of different antiepileptic drugs andnarcosis in different forms of status epilepticus in a retrospective study.

Method: We reviewed the medical charts of all patients, who were trea-ted for status epilepticus in our department from January 2000 to Decem-ber 2009. The last drug given before termination of status epilepticus wasconsidered as termination drug. The quotient of status epilepticus epi-sodes in which an antiepileptic drug or narcosis was the termination drugand all status epilepticus episodes in which the therapeutic agent hadbeen used was considered as efficacy rate. Differences in efficacy weretested for significance by chi-square-tests.

Result: 167 episodes of status epilepticus in 118 patients (58 female, 60male) could be evaluated. 9 patients died without termination of statusepilepticus. Efficacy rates ranged from 20% (Lacosamid) to 51% (Clo-nazepam) and 68% (narcosis). Efficacy of Phenytoin (44 episodes), Val-proate (53 episodes), Levetiracetam (41 episodes) and Lacosamid (10episodes) did not differ significantly. Clonazepam (121 episodes) wasmore efficient than other benzodiazepines (p < 0.000008) and i.v. antiepi-leptic drugs (p < 0.04). Narcosis was more efficient than i.v. antiepilepticdrugs (p < 0.005). But its efficiency was lower in nonconvulsive statusepilepticus than in status of generalized tonic-clonic seizures (p < 0.02).

Conclusion: The results of this retrospective study are confounded bymany factors. Nevertheless Clonazepam was more effective in the termi-nation of status epilepticus than other antiepileptic drugs und narcosisworked better in generalized tonic-clonic status epilepticus than in non-convulsive status epilepticus.


p333NON-CONVULSIVE STATUS EPILEPTICUS: PREVA-LENCE, PRECIPITATING FACTORS, CLINICAL MANI-FESTATIONS, RADIOLOGICAL,ELECTROENCEPHALOGRAPHIC FINDINGS ANDMORTALITY IN A TERTIARY CARE HOSPITAL INMEXICOV. Gij�n-Mitre*, M. Alonso-Vanegas�, and H. Sent�es Madrid�

*Instituto Nacional de Ciencias M�dicas y Nutrici�n SalvadorZubir�n, M�xico D.F, Mexico; �Instituto Nacional deNeurolog�a y Neurocirug�a Manuel Velasco Suarez, Mexico

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City, Mexico; and �Instituto Nacional de Nutrici�n y CienciasM�dicas Salvador Zubir�n, Distrito Federal, Mexico

Purpose: To determine the prevalence, causes, clinical features, radio-logical and EEG, treatment and mortality in patients with non-convulsivestatus epilepticus (NCSE) in the Instituto Nacional de Ciencias M�dicasy Nutrici�n Salvador Zubir�n.

Method: A retrospective, descriptive, observational study.

Result: Seventy-nine cases of status epilepticus (SE) of which 8 werefor NCSE (10.12%), 5 women, mean age 52 years, 3 had a family his-tory of epilepsy, 2 history of neonatal hypoxia, 5 had reported seizurespreviously, 2 by migralepsia, 1 traumatic brain injury, 1 as a complica-tion of chronic meningitis from tuberculosis and another one for cryp-togenic epilepsy, 2 had previously presented convulsive SE. 6 hadNCSE admission. The causes were diverse: meningoencephalitis (2),metabolic (2), suspension of drugs (1), migralepsia (2), 1 after cesti-cide treatment, 4 had initially behavior alterations, temporal disorienta-tion and focal seizures, 2 tonic-clonic seizures. The average Glasgowwas 9, all cases showed alteration of the alert and the duration waslonger than 30 minutes (prolonged SE) in 5 patient. The neuroimagingwas abnormal in 3 patients and the EEG showed unilateral epilepticactivity in 6 and bilateral in 2. The treatment was based on BZD andPHT in all patients, 4 underwent barbiturate coma, 2 had refractorySE. Mortality was 12.5% (1) and 1 patient was left with serious neuro-logical sequelae.

Conclusion: A history of epilepsy was common in patients with NCSE,the alert and conduct disorders were the main clinical manifestations,mortality appeared similar to that reported in the literature.

p334SUCCESSFUL USE OF KETAMINE IN PEDIATRICSUPER-REFRACTORY STATUS EPILEPTICUS – CASEREPORTC. Andrade*, S. FranÅa*, M. Sampaio*, A. Ribeiro�,J. M. Oliveira*, J. A. M. Ribeiro*, and R. Rego�

*Hospital de S¼o Jo¼o, Porto, Portugal; and �Servico deNeurofisiologia, Porto, Portugal

Purpose: Treatment failure in refractory status epilepticus (SE) and pro-gression to super-refractory SE may be related to a depletion of GABAreceptors, decreasing the efficacy of most general anesthetic drugs. Keta-mine, an antagonist of NMDA receptors, seems therefore a rationaloption in super-refractory SE. We report our experience using this drugon a pediatric case of super-refractory SE.

Method: Clinical case report.

Result: 5 year-old girl with DiGeorge syndrome, extensive bi-hemi-spheric polymicrogyria, severe psychomotor retardation and epilepsy.During the course of a respiratory infection the patient developed gen-eralized myoclonic SE. She was admitted in the ICU, where baselineanti-epileptic drug treatment was optimized and burst-suppression wasachieved with midazolam, propofol, thiopental or combinations ofthese drugs. However, tapering anesthetics repeatedly resulted in clini-cal and EEG evidence of recurrent SE. After 30 days of ICU stay, ke-tamine was tried, with rapid clinical and EEG response, allowing UCIdischarge one week later. At the 2-month follow-up visit, the patienthad complete clinical recovery, with a return to her baseline neurologi-cal status.

Conclusion: In this case of pediatric super-refractory SE, the responseto ketamine was prompt and sustained, despite being initiated one monthafter ICU admission. We speculate if an earlier use of this drug mighthave aborted the SE sooner. Further case reports and clinical trials of ke-tamine in super-refractory SE are needed.

p335DELAY IN DIAGNOSIS: A NEW PREDICTOR OFREFRACTORINESS AND MORTALITY IN NONCON-VULSIVE STATUS EPILEPTICUS?M. Sanchez, L. Romano, F. Latini, P. Alvarez, M. Ayala,A. Aleman, I. Etchepareborda, E. Sottano, P. Ioli, andS. GonorazkyHospital Privado de Comunidad, Mar del Plata, Argentina

Purpose: The mortality of non-convulsive status epilepticus (NCSE)ranges from 18 to 52% depending on the presence of different prognosticfactors. Recognizing these factors in NCSE helps to differentiate thegroup of patients requiring special care or benefit from specific therapeu-tic strategies.

Objective: To evaluate the delay in the diagnosis of NCSE as a predictorin refractoriness and mortality at day 30 in patients with NCSE.

Method: In this prospective study we recorded all cases of NCSEbetween April 2007 and March 2011, in patients ‡21 years. The baselineprognostic variables were analyzed using stepwise logistic regressionanalysis.

Result: There were 125 patients with NCSE. The median age was 76years and 65% were women. The etiology of NCSE was unknown in 9%,remote symptomatic in 10%, and in 81% acute symptomatic. The mediandiagnostic delay time was 48 hours. The mortality rate was 37%. Afteranalysis of all the aforementioned variables using stepwise logisticregression analysis, only delayed diagnosis >56 hs was an independentpredictor of refractoriness(OR:4.7, p = 0.0002). Acute symptomatic etiol-ogy (OR:7.2, p = 0.003), partial NCSE (OR:3.9, p = 0.008), delayed diag-nosis >56 hs (OR:4.6, p = 0.001), and refractoriness (OR:5.3, p = 0.0008)were independent predictors of mortality at day 30 in patients withNCSE.

Conclusion: Our data suggest that a delayed diagnosis is an independentvariable of refractoriness and mortality in patients with NCSE. We pro-pose that delayed diagnosis should be included as a prognostic variablewhen analyzing the efficiency of different treatments for this entity. Ourfindings should be confirmed in future prospective studies in differentpopulations.

p336IN HOSPITAL DEATHS ASSOCIATED WITH STATUSEPILEPTICUS: A DR FOSTER ALERTE. F. Cant*, G. Cook�, C. Wasson�, and P. Talbot�

*Manchester University, Manchester, UK; �Stepping HillHospital, Manchester, UK; and �Salford Royal Hospital,Manchester, UK

Purpose: Dr Foster highlighted Stepping Hill hospital as having anabnormally high number of deaths among patients with a primary dis-charge code of status epilepticus (SE) from 2000–2011. This auditfocused on why this occurred and if improvements could be made to pre-vent this in the future.

Method: The notes of 15 out of the 17 patients who died with a dis-charge diagnosis code of G41 (SE) from 2000–2011 were audited assess-ing the care given in hospital and to determine whether the death wasavoidable.

Result: All patients were admitted in SE and had a mean age of 76. Theywere found to have significant comorbidities such as dementia, cerebro-vascular disease and excess alcohol consumption. All had appropriateimmediate management against guidelines. 8 patients were given phenyt-oin during admission;4 did not have their serum levels monitored and 4

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had sub-therapeutic serum levels. 1 patient's ITU admission was delayed,1 other patient may have been appropriate for ITU but referral was notdiscussed. 1 died from a pulmonary embolism.

Conclusion: These deaths were unavoidable due to severe underlyingdisease triggering the seizures. The alert was due to inaccurate dischargecoding where the primary diagnosis was inappropriately given as SE.However the audit of the management of SE highlighted areas forimprovement. These included a need for closer and more rigorous moni-toring of therapeutic Phenytoin levels; greater patient review for ICU andquicker transfer; optimising DVT prophylaxis early in SE managementand the consistent use of measures to prevent aspiration. Updated guide-lines are being implemented.

p337THE IMPACT OF NEWER ANTIEPILEPTIC DRUGS INTHE TREATMENT OF STATUS EPILEPTICUSA. O. Rossetti, and L. JaquesCHUV, Lausanne, Switzerland

Purpose: Newer antiepileptic drugs (AED) are increasingly prescribed,and seem to have a comparable efficacy as the classical AED in patientsliving with epilepsy; however, their impact on status epilepticus (SE)prognosis has received little attention.

Method: In our prospective SE registry (2006–10) we assessed the useof newer AED (for this purpose: levetiracetam, pregabalin, topiramate,lacosamide) over time, and its relationship to outcome (return to clinicalbaseline conditions, new handicap, or death). We adjusted for recognizedSE outcome predictors (Status Epilepticus Severity Score, STESS; poten-tially fatal etiology), and the use of >2 AED for a given SE episode.

Result: Newer AED were used more often towards the end of the studyperiod (42% versus 30% episodes), and more frequently in severe anddifficult to treat episodes. However, after adjustment for SE etiology,STESS, and medication number, newer AED resulted independentlyrelated to reduced likelihood of return to baseline (p < 0.01), but not toincreased mortality. STESS and etiology were robustly related to bothoutcomes (p < 0.01 for each), while prescription of >2 AED was onlyrelated to lower chance of return to baseline (p = 0.03).

Conclusion: Despite increase in the use of newer AED, our findingssuggest that SE prognosis has not been improved. This appears similar torecent analyses on patients with refractory epilepsy, and corroborates thehypothesis that SE prognosis is mainly determined by its biological back-ground. Since newer AED are more expensive, prospective trials show-ing their superiority (at least regarding side effects) appear mandatory tojustify their use in this setting.

p338CORTICOSTEROIDS IN THE TREATMENT OF NON-CONVULSIVE STATUS EPILEPTICUS (NCSE)D. Tsiptsios, D. Kiourtidis, T. Tsironis, P. Petrou, E. Ameridis,M. Krommida, A. Mastrokosta, E. Markousi, G. Deretzi,E. Koutlas, J. Rudolf, A. Tichalas, G. Xiromerisiou, X. Fitsioris,and I. TsiptsiosPapageorgiou General Hospital, Thessaloniki, Greece

Purpose: NCSE is a neurological condition that is often missed or mis-diagnosed in emergency neurology when immediate EEG recording isnot available. Due to this fact NCSE often becomes refractory, ie lasting>24 hours. The aim of this study is to investigate the efficacy of high-dos-age corticosteroid treatment in refractory NCSE.

Method: During a 19 month period, June 2010 – February 2012, 27patients were diagnosed with NCSE based on EEG patterns, such asPLEDs, GPEDs and BiPEDs.

15 cases became refractory despite aggressive treatment with IV Ben-zodiazepines, Phenytoin, Valproate and Levetiracetam.

1 g Methyprednisolone for 5 days was administered to all 15 cases. Inthe meantime, the aetiology of NCSE was verified. Frequent follow-upEEG recordings were performed.

Result: 7 patients clinically deteriorated, their EEG patterns remainedunchanged and died within weeks or months afterwards. The mean agewas 68.5 and the underlying disease was brain tumor (4 cases), herpessimplex encephalitis (HSE) (1), acute disseminated encephalomyelitis(ADEM) (1) and Creutzfeldt – Jacob disease (1).

Clinical improvement and EEG normalization was evident in 8 cases.The mean age was 48 and the underlying disease was neurosarcoidosis (1case), Systemic Lupus Erythematosus (1), ADEM (1), stroke (2), Alzhei-mer's Disease (1) and HSE (1).

Conclusion: High-dosage corticosteroid treatment should always beconsidered in the treatment of refractory NCSE. Furthermore, the clini-cal outcome is strongly influenced by the underlying disease and thepatient's age.

p339NONCONVULSIVE STATUS EPILEPTICUS IN NOR-MOGLICEMIC DIABETIC PATIENTSJ. Klem*, L. Stancetic Bacvanin�, and A. Bacvanin�

*General Hospital, Sombor, Serbia; and �General Hospital,Sremska Mitrovica, Serbia

Purpose: Nonconvulsive status epilepticus (NCSE) causes many differ-ent neurologic deficits, particularly in alertness and cognitive function,and may be one of the most frequently missed diagnoses in patients withaltered neurologic function. NCSE may constitute one quarter up to 40%of all status epilepticus. Diabet type 1 can cause an acute confusionalstate due to NCSE.

Method: In our two 48 and 65 years-old patients, the lack of a pre-dominant motor component differentiates NCSE from convulsive sta-tus epilepticus. First they were seen with bizarre, and fluctuatingbehaviour from lack of responsiveness to confusion with oral or man-ual automatisms lasting 4–8 hours before hospital addmision. Duringhospitalization altered mental status, subtle twitching, blinking, nystag-mus, stupor and confusion were seen. They were diabetic. They hadnormal blood sugar levels . Both patients have had history of oftencomatose hypoglicemic states with generalized convulsiones due tolow blood sugar levels.

Result: laboratory screening including normal blood sugar levelsshowed no abnormalities . EEG showed prolonged repetitive complexpartial seizures and/or continuous seizure activity in both patients.Computed tomography showed reductive cortical changes . After phe-nobarbital administration in the next 3–4 days, they became moreresponsive, and oral or manual automatism slowly resolved . Up tonext 10 days after NCSE they were amnestic, and their verbal functionrecovery delayed.

Conclusion: NCSE may occur in patients with diverse clinical diagno-ses. Preventing missed diagnosis, EEG should be perfomed in allpatients with unexplained reccurent altered mental status, stupor andconfusion.

p340FOCAL MYOCLONUS STATUS IS NOT UNCOMMONMANIFESTATION IN THE PATIENTS WITH ANTIFOS-FOLIPID SYNDROMEL. M. Stancetic Bacvanin*, J. Klem�, and A. G. Bacvanin**Srem.Mitrovica, Serbia; and �Sombor, Serbia

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Purpose: We present patients with antifosfpolipid syndrome (APS) andfocal myoclonic status.

Method: A medical files of 25 patients with APS (16 femals and 9males) that were hospitalized from April 1999 to August 2010 in ourdepartment were evaluated.

Result: We found four patients (16%) that had prolonged myoclonic sei-zures in their medical history. Myoclonic status lasted from 12 hours to10 days . Half of the patients had secondary APS. Reccurent palatalmyoclonus had 46 years-old female with brainstem vasculitic changes,52 years-old female had hemiclonic status and bilateral brachial spinalmyoclonic yerks.. Two men (52 and 65 years-old) had prolonged hemifa-cial myoclonic yearks . All patients were MRA pozitive to focal cerebralischemia and focal cortical atrophy changes and all had increased titersof anticardiolipin antibodies (IgG 24,3–52 GPLU/ml; IgM 14–62,9MPLU/ml). Patient with Epilepsia partialis continua Kozevnikow hadexcessive unilateral or bilateral frontocentral polyspikes and spike wavesdischarges . During spinal myoclonic yearks there was no EEG-epilepticactivity. MRI showed left focal frontotemporal atrophy. Patient with pal-atal myoclonus had frontocentroparietal polyspikes, and frontal slowactivity on its EEG. MRI showed lacunar vascular supratentorial andbrainstem ischemic lesions. Two men with hemifacial myoclonia had nospecific EEG changes after the attacks. One had luetic gummous forma-tion, the other microlacunar and extended predominantely temporal corti-cal atrophy.

Conclusion: In this group four patients (16%) had prolonged myoclonicseuzures . Seizures were partially ameliorated by a complex of medica-tions: anticonvulsants and pulse corticosteroid therapy.

p341SUPER-REFRACTORY STATUS-EPILEPTICUS: THEREIS ALWAYS HOPEZ. Agirre-Arrizubieta*, and N. Moran�

*King's College Hospital, London, UK; and �East KentHospitals NHS University Foundation Trust, Canterbury, Kent,UK

Purpose: Two male patients, 20 and 28 years, presented with acute sei-zures and encephalopathy. Multiple brain MRI examinations were nor-mal and extensive metabolic, haematological and serological tests werenegative. Cerebrospinal fluid (protein, glucose, microbiology, oligoclo-nal bands) was normal except patient A had 7 white cells/ml. Bothreceived broad spectrum antimicrobials.

Method: In patient A generalized tonic-clonic seizures led to ventilationand ultimately treatment with six anti-epileptic drugs (AED). The EEGinitially showed a suppression burst pattern; following reduction of seda-tion, status epilepticus (SE) with a right temporal focus, plus generalizedperiodic epileptiform discharges (GPEDs). It was some three monthsbefore control was achieved but recovery was good with mild amnesiaonly.

Result: Patient B had focal seizures with secondary generalization andthen SE. The EEG revealed a right anterior focus, generalized seizuresand GPEDs. He was ventilated and subsequent treatment comprisedseven AED, including thiopentone, plus human pooled immunoglobulinand plasmapheresis. Six months following presentation, deep brain stim-ulation as associated with substantial improvement in the EEG but thepatient was left in a persistent vegetative state.

Conclusion: Each patient displayed similar clinical pictures of obscureaetiology with super-refractory SE (SRSE) (Shorvon S. Epilepsia. 2011Oct;52 Suppl 8:53–6). However, the outcomes were radically different.Even when prolonged and of unknown aetiology, SRSE should not beregarded as hopeless.

p342USE OF INTRAVENOUS LACOSAMIDE IN STATUS EPI-LEPTICUS AND CLUSTER SEIZURESY. Handouk, C. Bomprezzi, C. Minardi, S. Malag�, S. Morresi,and A. MauroU.O. Neurologia, Cesena, Italy

Purpose: To test the efficacy and safety of the intravenous drug formu-lation in SE and cluster seizures.

Some antiepileptic drugs (AEDs) used in status epilepticus (SE) areassociated with potential respiratory and cardiovascular complications.Lacosamide (LCM), a new AED, has an intravenous formulation with apotential role in the treatment of SE.

Method: 11 patients with symptomatic epilepsy (6 female and 5 male;mean age 66 (23–90); 8 with SE and 3 with cluster seizures), was treated,after failure of other AEDs, with simultaneous administration of intrave-nous and oral LCM for two days (200 mg intravenous + 50 mg oral LCMtwice daily), then switched to oral LCM (400 mg daily).

Result: EEG improvement occured in the first 24 hours after the begin-ning of LCM therapy. All patients were responsive with no seriousadverse event, except two old patients who died for severe comorbidities.

Conclusion: LCM could be efficacious and safe in the treatment of SE.


p343THE EFFECTS OF ANTIEPILEPTIC DRUGS ON THEVOLTAGE-GATED SODIUM CHANNELS OF THEPERIPHERAL MYELINATED NERVE FIBERS OF THEADULT RATG. Zafeiridou*, A. Kagiava�, M. Spilioti�, A. Karlovasitou�, andG. Theophilidis�

*Aristotle University, Thessaloniki, Greece; �School of Biology,Aristotle University, Thessaloniki, Greece; and �MedicalSchool, Aristotle University, Thessaloniki, Greece

Purpose: One of the major targets of many widely used antiepilepticdrugs (AEDs) are voltage-gated sodium channels (VGSCs). Some ofthese drugs have been associated with effects on the peripheral nervefunction. In this study we investigated in vitro the effects of three AEDson the VGSCs of the peripheral myelinated nerve fibres, of the adult rat.

Method: The effects of phenytoin (PHT), topiramate (TPM) and lacosa-mide (LCM) were tested on the electrophysiological properties of the Wi-star rat isolated sciatic nerve.

Result: Incubation of the sciatic nerve fibers in therapeutic doses (72.9,36.46, 18.23 lM) of PHT, caused a gradual decreased in the amplitude ofthe CAP and increase in the latency (p < 0.05). TPM was applied at muchhigher concentrations than the therapeutic doses (178.5 Mm, 500 lM),yet it had no effect on the amplitude of the CAP and the latency (p >0.05). LCS was also investigated at high concentrations (100, 250, 400,500 lM) but in this case, an acute, dose-respondent, decrease in theamplitude of the CAP was caused (p < 0.001). This intense decrease inamplitude was followed by a similar increase in the latency (p < 0.001).

Conclusion: These findings confirm the adverse effect of PHT, in theperipheral nerve function even in very low concentrations. In contrast,LCS had effects at concentrations much higher than the therapeuticdoses. LCS also demonstrates a different mode of action that causes rapid

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and acute alteration on the electrophysiological properties of the periph-eral nerve. Finally, TPM had no effects on the peripheral nerve function,although high concentrations were used.

p344A NEW IN VITRO MODEL OF HIGH FREQUENCYELECTRICAL STIMULUS INDUCED SEIZURE ANDEFFECTS OF STANDARD ANTIEPILEPTIC DRUGSA. Wahab*, K. Albus�, and U. Heinemann�

*University of Karachi, Karachi, Pakistan; and �Charit� –Universitatsmedizin Berlin, Berlin, Germany

Purpose: In the hippocampus intense high frequency electrical stimula-tion induces a long lasting rhythmic synchronization (primary afterdis-charge). In order to examine the suitability of primary afterdischarges(PADs) in organotypic hippocampal slice cultures (OHSCs) as an in vitromodel of evoked seizures we have investigated in detail the sensitivity ofPADs to standard antiepileptic drugs (AEDs).

Method: OHSCs were prepared using interface culture method fromeight to 11 day old Wistar rats. A PAD in CA1 was elicited by stimulatingthe stratum radiatum with an intensity of two times that required to elicita maximal population spike. The effects of AEDs on the duration and onfrequency properties of PADs and the tonic-like and clonic-like subdivi-sions of PADs were determined and EC50 values were calculated fromconcentration – response curves.

Result: All the standard AEDs except ethosuximide reduced the dura-tions of PADs and tonic-like and clonic-like subdivisions of PADs. Theeffects were concentration dependent and reversible. The effects on sub-divisions of PADs differed between AEDs. Carbamazepine and phenyt-oin shortened the tonic-like and clonic like subdivisions at similarproportions whereas phenobarbital, diazepam and valproic acid preferen-tially shortened the clonic-like subdivision. Diazepam at low concentra-tions increased the duration of tonic- like subdivisions an effect not seenwith the other AEDs. The suppressive effects of AEDs on frequencyproperties observed only at higher concentrations.

Conclusion: We conclude that the PAD test in OHSCs is a suitable in vi-tro model of evoked seizures. The validity of this model could be furtherexamined by studying the effects of newer AEDs.

p345PENUMBRA REGION EXCITABILITY IS NOTENHANCED ACUTELY AFTER CEREBRAL ISCHEMIAIN THE IN VITRO ISOLATED GUINEA PIG BRAING. L. Breschi*, A. Mastropietro�, I. Zucca�, L. Librizzi*, andM. De Curtis�

*Neurological Inst. C. Besta, Milano, Italy; and �I.R.C.C.S.Foundation Neurological Institute, Milan, Italy

Purpose: Early seizures are a frequent consequence of stroke. The maingoal of the present study is to verify whether anoxic ischemia per se isable to induce early changes in excitability that may be a prelude to thegeneration of seizures and, ultimately, to epileptogenesis. Excitabilitychanges in the very acute postischemic phase are here analyzed in a newmodel of ischemia developed in the isolated guinea pig brain preparation.

Method: Permanent bilateral occlusion of the anterior cerebral arteries(ACAs) was performed in the isolated guinea pig brain maintained in vi-tro by arterial perfusion. Magnetic resonance imaging and immunohisto-chemistry were utilized to identify the penumbra and core regionsinduced by ACA occlusion (ACAo). Slow potentials and evokedresponses recorded in olfactory cortices were utilized to evaluate excit-ability changes in the acute phase after ischemia.

Result: ACAo induces a core area located in the shell of the nucleus ac-cumbens and a region of penumbra in the underlying olfactory cortices,

where characteristic slow potential shifts, but no reduction of diffusiontensor magnetic resonance (MR) signal and MAP-2 immuno-staining(typical of ischemic core) was observed. Recording of responses evokedby low- and high-frequency stimulations of the lateral olfactory tractshowed no excitability changes in the early hours that follow ischemia inthe olfactory cortical areas supplied by ACAs.

Conclusion: The absence of early hyperexcitability changes in an iso-lated whole brain model of ischemia, strongly suggests that brain anoxiaper se does not contribute to the generation of early seizures. These find-ings support the view that blood-borne events (such as hemorrhage andinflammation) may play a major role in early postischemic seizures.

p346INVESTIGATION OF ANTIEPILEPTIC DRUG TRANS-PORT BY SOLUTE CARRIERS OATP1A2 AND MCT1H. L. Jones, D. Dickens, A. Owen, M. Pirmohamed, andG. J. SillsUniversity of Liverpool, Liverpool, UK

Purpose: We have investigated the trans-membrane transport of antiepi-leptic drugs (AEDs) by organic anion transporting polypeptide 1A2(OATP1A2) and monocarboxylic acid transporter 1 (MCT1), membersof the solute carrier super-family.

Method: Xenopus laevis oocytes were transfected with OATP1A2/MCT1 cRNA and transport determined three days thereafter by compari-son of the uptake of radiolabelled AEDs (25 mM phenytoin, 20 mM car-bamazepine, 300 mM sodium valproate, 10 mM lamotrigine, 10 mMgabapentin, 10 mM topiramate and 6 mM levetiracetam) in transfected vsuntransfected oocytes. Estrone-3-sulfate (1 lM) and lactic acid (5 lM)were employed as positive control compounds for OATP1A2 and MCT1,respectively. Results from at least three independent replicates, eachemploying eight oocytes per group, were expressed as mean (€SEM) per-centage of control transport in untransfected oocytes.

Result: Transport of estrone-3-sulphate in OATP1A2-transfectedoocytes was 1326 € 171% of that observed in untransfected controls (p <0.01). Transport of lactic acid in MCT1-transfected oocytes was 2607 €240% of that observed in untransfected controls (p < 0.001). There wereonly minor changes in the mean transport of AEDs in transfected vsuntransfected oocytes for both OATP1A2 (98.1 € 8.2% phenytoin, 91.3€ 2.8% carbamazepine, 111 € 7.3% sodium valproate, 128 € 7.7%lamotrigine, 104 € 17% gabapentin, 111 € 6.5% topiramate, 94.5 € 7.0%levetiracetam) and MCT1 (108 € 2.6% phenytoin, 110 € 4.1% carbamaz-epine, 94.0 € 3.8% sodium valproate, 77.6 € 5.7% lamotrigine, 164 €15% gabapentin, 110 € 3.0% topiramate, 115 € 5.9% levetiracetam),none of which reached statistical significance.

Conclusion: None of the seven AEDs investigated in this studyappeared to be a substrate for either OATP1A2- or MCT1-mediatedtransport in selectively transfected Xenopus laevis oocytes. These find-ings discount the involvement of OATP1A2 and MCT1 in the trans-membrane transport of AEDs.

p347L-TYPE VOLTAGE GATED CALCIUM CHANNELSAFFECT SEIZURE-LIKE ACTIVITY IN AN AMBIVA-LENT MANNER, BUT PROMOTE THE INDUCTION OFPAROXYSMAL DEPOLARIZATION SHIFTSH. Kubista, L. Rubi, M. Lagler, P. Geier, K. Dasgupta, andS. BçhmCenter of Physiology and Pharmacology Medical University ofVienna, Vienna, Austria

Purpose: The role of L-type voltage-gated calcium channels (LTCCs)as regulators of neuronal excitability relies on the coupling of

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LTCC-mediated Ca2 + -influx to Ca2 + -dependent conductances. Wehave shown previously that in moderate (with respect to duration andamplitude) depolarisations excitatory Ca2 + -activated nonspecific cationchannel-activation prevails, which diminishes and gives way to the acti-vation of hyperpolarising Ca2 + -dependent potassium channels as thedepolarization grows. These findings prompted us to test in a similarapproach the effects of LTCC modulation on (long-lasting) seizure-likeactivity (SLA) and on (brief) paroxysmal depolarization shifts (PDS).

Method: Current-clamp experiments were performed on primary hippo-campal neurons. SLA was induced by pharmacological means (e.g. low-Mg2 + buffer). Induction of PDS was facilitated by caffeine. LTCC activ-ity was modulated by BayK 8644 (LTCC agonist) and isradipine (antago-nist).

Result: Potentiation of LTCCs affected SLA activity in opposing man-ners, leading to enhancement involving plateau potentials on the onehand and reduction involving more pronounced after-hyperpolarisationson the other hand. Caffeine alone was hardly sufficient to induce PDS,but PDS were readily induced when LTCC activity was augmented byco-application of BayK.

Conclusion: The bimodal effects of LTCC activation on excitability canbe extended to epileptiform discharges. Hence, therapeutic reduction ofLTCC activity may have little beneficial or even adverse effects on epi-leptic seizures. However, our data identifies enhanced activity of LTCCsas one precipitating cause of PDS. Because evidence is continuouslyaccumulating that PDS represent important elements in epileptogenesis,LTCC inhibitors may prove useful in anti-epileptogenic therapy (sup-ported by the Austrian Science Fund, project P-19710).

p348PATTERNS OF SYNCHRONOUS POPULATION ACTIV-ITY IN THE NEOCORTICAL TISSUE OF EPILEPTICAND NON-EPILEPTIC TUMOR PATIENTS, IN VITROK. T�th*, �. Kandr�cs�, C. Szab��, A. Bag��, L. Er}oss�, L. Entz�,P. Orbay�, S. Czirj�k�, P. V�rady�, L. Sipos�, T. Freund§,I. Ulbert–, and L. Wittner–

*Institution of Experimental Medicine, HAS, Budapest,Hungary; �P�zm�ny P�ter Catholic University, Budapest,Hungary; �National Institute of Neuroscience, Budapest,Hungary; §Institute of Experimental Medicine, HungarianAcademy of Sciences, Budapest, Hungary; and –Institute forPsychology, Hungarian Academy of Sciences, Budapest,Hungary

Purpose: The subiculum and hippocampal CA2 region of patients withtemporal lobe epilepsy generate spontaneous population bursts in vitro,which is thought to be in relation with the epileptic reorganization. Weasked whether neocortical tissue of epileptic patients generates similarspontaneous synchronous population activity (SSPA). As control we usedtissue of patients with brain tumor, without epilepsy.

Method: Slices were prepared from the postoperative tissue and thelocal field potential gradient (LFPg) was recorded. Pyramidal cells werecharacterised in intracellular records.

Result: 48% of epileptic and 42% of tumor slices displayed SSPA.SSPAs were characterized by LFPg transient superimposed with high fre-quency oscillations and increased multi unit activity. The pattern ofSSPAs varied among the samples, but all types were present in both epi-leptic and tumor samples in a similar ratio. In 60% of the cases SSPAswere observed in the supragranular layers. Cell clustering analysisshowed that ~67% and ~50% of the cells increased their firing rates inrelation to SSPA, in epileptic and tumor slices, respectively. Generally,the discharge rate of supragranular cells was enhanced before the LFPgpeak, whereas infragranular cells fired after it. 2/3 of the intracellularrecorded cells showed depolarizing responses during SSPAs.

Conclusion: Our results suggest that neocortical slices derived fromboth epileptic and tumor patients can generate multiple types of SSPA.Supragranular layers might have a leading role in the generation ofSSPA. Features of SSPA were similar in epileptic and tumor slices, indi-cating that the emergence of neocortical SSPAs may not be related to epi-leptic processes.

p349SYNAPTIC AND NON-SYNAPTIC MECHANISMSUNDERLYING SUPPRESSION OF EPILEPTIFORMACTIVITY IN THE SUBICULAR NEURONS OF THEHIPPOCAMPUSN. Sah, and S. K. SikdarIndian Institute of Science, Bangalore, India

Purpose: Proper balance of neuronal activity is essential for normalbrain function. When the balance is compromised, neurological disordersmay result. Temporal lobe epilepsy (TLE), a neurological disorder, is themost common form of adult focal epilepsy. The purpose of this study wasto characterize the cellular and population dynamics of subiculum underhyperexcitable conditions.

Method: 4-Amino Pyridine with reduced magnesium model of epilepsywas used in this study. Cellular and population electrical activity wasrecorded through whole cell patch clamp and local field potential record-ing techniques.

Result: We have observed a distinct phenomenon in subiculum whereinan early hyperexcitable phase was followed by a late silent phase (LP)upon application of 4-AP. Silent state in pyramidal neuron was character-ized by periodic inhibitory post-synaptic potentials (pIPSPs) at a fre-quency of 0.2–1 Hz. GABAA receptor mediated inhibition coincidedwith excitatory inputs to countermand burst discharges. Gap junctionswere found to be critical for these pIPSPs generation. Fast spiking inter-neurons showed bursting discharges during the silent phase which mightbe triggering pIPSPs. The pIPSPs in pyramidal neurons ceased if theCA1-alveus was fissured. A strong coupling between CA1 discharge andsubicular pIPSPs indicates an important role of CA1 region.

Conclusion: We conclude that the action of feed forward inhibition con-certed by gap-junctions triggered homeostatic control leading to suppres-sion of epileptiform activity in subiculum, during the late phase (LP).Our work suggests that gap junctions are important in suppression of epi-leptiform activity in subiculum and argues the general notion of gap junc-tions being pro-epileptic.

p350EPILEPTIFORM ACTIVITY IN THE PIRIFORM COR-TEX AFTER 4AP ADMINISTRATION IN THE ISO-LATED GUINEA PIG BRAINL. M. Uva, F. Trombin, G. Carriero, and M. De CurtisFondazione IRCCS Istituto nazionale Neurologico, Milano, Italy

Purpose: We recently showed that arterial application of the K+ channelblocker 4-aminopyridine (4AP) induces two different and independentseizure-like event (SLE) patterns in the olfactory and limbic regions(Carriero et al., 2010). We further characterize here the network and cel-lular features of SLEs in the olfactory cortices.

Method: 4AP was arterially administered (50 lM; 5 min) or locallyinjected (2.5 mM) in the in vitro isolated guinea-pig brain. Field poten-tials (FPs) were simultaneously recorded from different limbic subre-gions. Simultaneous extracellular and intracellular recordings and [K+]o

shifts were recorded to characterize the activity in PC.

Result: We observed runs of fast activity (FRs) and SLEs featuring runsof high frequency activities superimposed to slow components followed

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by a serie of spikes. Lesions and local 4AP applications demonstratedthat SLEs initiate in PC. We found that layer II neurons discharged duringFRs and that during SLE there was a progressive inactivation of firingthat was blocked at the peak of the membrane depolarization andresumed during the spikes. The firing block was rescued injecting hyper-polarizing current, suggesting a depolarization block. We found the abol-ishment of the evoked response during SLEs after lateral olfactory tractstimulation and a partial recovery during the spikes. Simultaneousrecordings of FPs and [K+]o shifts showed a gradual [K+]o increase duringFRs and a secondary faster increase during SLEs. Synaptic activityrecovers after synchronous spiking and levels of [K+]o recovered.

Conclusion: The PC is the generator of the described activities. Weobserved a hypo-excitable status of PC networks that initiates a focal sei-zure-like discharge.

p351HOW DO CHANGES IN GABAB RECEPTOR EXPRES-SION AFFECT IDIOPATHIC GENERALISED EPILEPSYPHENOTYPES? (LITERATURE REVIEW)G. SummonsCardiff University, Maidenhead, UK

Purpose: GABA undergoes complex receptor modulations in epileptictissue, forming inhibitory and excitatory networks. GABAB receptors(GABABRs) underlie various phenotypes of Idiopathic Generalized Epi-lepsy (IGE). Generally, GABAB agonists exacerbate absence seizures.GABAB antagonists reduce absences. Convulsive seizures may beinduced by GABABR inhibition, and alleviated by GABAB agonists.GABABR isoforms – B1a, B1b and B2 – perform specific roles allowingnormal GABABR functioning, hence directly impact IGE phenotypes.Controversially, atypical absence seizures have been observed in GA-BAB knockout models, implying a contradiction to prior research.

Method: A metasearch was conducted to determine how altered GAB-ABRs in rodent models produce different IGE phenotypes, producing 28articles.

Result: A minority of papers noted normal GABABR expression in typi-cal absence seizures, contradicted by pharmacological studies where theywere exacerbated by GABAB agonists. Other studies showed increasedGABABR expression with age and seizure occurrence. This was attrib-uted to increased neocortical GABAB autoreceptor expression andincreased presynaptic GABAB thalamic expression. Transgenic upregu-lation of B1a and B1b induced atypical absence seizures in thalamocorti-colimbic networks. Knockout studies in corticolimbic networks causedclonic seizures. Atypical absences were only observed in a minority ofGABAB1-/- mice. Seizure severity is subtype specific; B1a rescued theclonic phenotype, and increased absence severity when upregulated.

Conclusion: Absence seizures are predominantly caused by excess inhi-bition in thalamocortical networks, due to increased GABABRs expres-sion; these seizures become atypical when GABABRs are upregulated inthe limbic network. Clonic seizures are associated with reduced GA-BABR expression. Seizure severity is modulated by varying expressionof GABAB subtypes.

p352THE OREXIN PATHWAY IS NOT INVOLVED IN THEATTENUATION OF LIMBIC SEIZURES BY DES-ACYLGHRELINJ. Coppens, J. Portelli, Y. Michotte, and I. SmoldersVrije Universiteit Brussel, Brussels, Belgium

Purpose: Once considered inactive, des-acyl ghrelin is now implicatedin a number of biological functions. Unlike ghrelin, des-acyl ghrelin isunable to activate the ghrelin receptor and recently one study implied that

intracerebroventricular des-acyl ghrelin administration affected foodintake via the orexin pathway. Recently, des-acyl ghrelin has been pro-posed to have beneficial effects on limbic seizures. In this study, we fur-ther characterised the role of des-acyl ghrelin in seizures using the focalpilocarpine model for limbic seizures.

Method: In this study we used the in vivo rat model for pilocarpine-induced limbic seizures. Intrahippocampal administration of des-acylghrelin, the dual orexin receptor antagonist almorexant, or co-administra-tion of des-acyl ghrelin and almorexant was performed in rats for 2 hprior subsequent administration of pilocarpine directly in the hippocam-pus. Rats were monitored following pilocarpine perfusion, and seizurebehavior grades were evaluated according to a modified Racine's scale.

Result: We noted that while des-acyl ghrelin attenuated pilocarpine-induced limbic seizures at different concentrations, almorexant did notaffect seizure severity. To determine whether des-acyl ghrelin utilizes theorexin pathway for its anticonvulsant effect, des-acyl ghrelin was co-administered with almorexant. Dual orexin receptor blockade did not pre-vent des-acyl ghrelin's anticonvulsant effect.

Conclusion: We confirmed that des-acyl ghrelin attenuates limbic sei-zures and established that the orexin pathway is not involved. This is alsofirst evidence that simultaneous antagonism of hippocampal orexinreceptors does not affect seizure severity. This study highlights the needof identifying the mechanism of action of des-acyl ghrelin in epilepticseizures.


p353ANTI-SEIZURE ACTION OF THE ANTIDEPRESSANT,SERTRALINEM. Sitges, and B. I. AldanaInstituto de Investigaciones Biom�dicas, Universidad NacionalAut�noma de M�xico, M�xico D.F., Mexico

Purpose: Investigate the potential anticonvulsive action of sertraline, asrecently we found that sertraline inhibits cerebral presynaptic Na+ chan-nels controlling release of the excitatory amino acid neurotransmitter glu-tamate (Aldana & Sitges J Neurochem 2012; in press); like severalantiepileptic drugs do (Sitges M et al. Neuropharmacology 2007;52:598–605).

Method: Pentilenetetrazole (PTZ, 50 mg/kg i.p.)-induced seizures andcortical excitability changes, as judged by the EEG highest peak ampli-tude value (HPAV), were respectively evaluated in non anesthetized andin anesthetized animals previously administered with: vehicle (controlgroup), sertraline (range from 1.5 to 25 mg/kg) and carbamazepine (15and 25 mg/kg), as positive control.

Result: In all the non anesthetized animals injected with vehicle the firstgeneralized tonic-clonic seizure was presented near the first minute fol-lowing PTZ and 40% of the animals died. In animals administered with2.5 mg/kg sertraline the latency of the first seizure to PTZ increased andits duration decreased but seizures were not prevented. At a high dose (25mg/kg) sertraline completely prevented seizures to PTZ. None of the ani-mals pre-administered with sertraline at any dose died. In the anesthe-tized animals injected with vehicle, the baseline EEG HPAV (42 € 1 lV)increased to 164 € 6 lV in the first 120 s interval following PTZ. ThisPTZ-induced increase in the HPAV was: insensitive to 15 mg/kg carba-mazepine, lost in half of the animals injected with 2.5 mg/kg sertralineand absent in all the animals injected with sertraline above 5 mg/kg orwith 25 mg/kg carbamazepine. None of the anesthetized animals died.

Conclusion: Present findings demonstrate the anti-seizure effect ofsertraline.

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p354PROTEOMIC PROFILING OF THE HIPPOCAMPUS OFEPILEPTIC MICE WITH AND WITHOUT SCLEROSISA. Mago*, K. A. Kekesi�, A. Simor�, K. T�th�, E. Hunyadi-Gulyas§, Z. Darula§, K. Medzihradszky§, T. Freund*, G. Juhasz–,and Z. Magloczky**Institute of Experimental Medicine, Hungarian Academy ofSciences, Budapest, Hungary; �Eçtvçs Lor�nd University, Inst.Biology, Budapest, Hungary; �Institution of ExperimentalMedicine, HAS, Budapest, Hungary; §Biological ResearchCentre, Hungarian Academy of Sciences, Szeged, Hungary; and–Eçtvçs Lor�nd University, Inst. Biology, Research Group ofProteomics, Budapest, Hungary

Purpose: Abnormal expression of certain proteins was found in neuro-degenerative diseases. We analyzed proteomic networks in the pilocar-pine-model of epilepsy in mice.

Method: After one-month survival the animals were sacrificed and thebrain was removed. The right hippocampus was processed for proteomicanalyses, the left one for morphological characterization. Proteins wereseparated by 2-dimensional gel electrophoresis, and identified by Liquidchromatography-mass spectrometry. Animals were classified on thebasis of the hippocampal cell loss as non-sclerotic or sclerotic.

Result: We examined the proteomic alterations compared sclerotic tocontrol and non-sclerotic to sclerotic animals. A network was built fromthese proteins using Ariadne Genomics Pathway studio software estab-lishing direct interactions of proteins, and their relationships with schizo-phrenia, Alzheimer's disease (AD), Parkinson's disease, temporal lobeepilepsy and anxiety. In the networks there were 54 out of 93 (in case ofcontrol-sclerotic) and 44 out of 82 (in case of non-sclerotic-sclerotic) pro-teins with at least one interaction with protein or disease. These proteinswere analyzed by establishing three functional groups: metabolisms, syn-aptic and receptor functions and cytosceleton. Their contributions in epi-leptic reorganization are analyzed. Overlap with other neurologicaldisorders was found. The altered proteins showed the most connectionwith AD and the least connection with anxiety.

Conclusion: On the basis of the data, some neurological diseases mayhave overlapping molecular mechanisms. Furthermore, no direct interac-tions with proteins/diseases were found in the networks in case of certainproteins. It might mean that available data about the functions and inter-actions of proteins are incomplete in the scientific literature.

p355BENEFITS OF AEROBIC EXERCISE FOR ADULT RATSWITH SEIZURES INDUCED BY HOMOCYSTEINETHIOLACTONED. Hrncic*, A. Rasic-Markovic*, R. Sarhan�, V. Susic�,D. Macut*, D. Djuric*, and O. Stanojlovic**Belgrade University School of Medicine, Belgrade, Serbia; �

Menoufia University Faculty of Medicine, Tanta, Egypt; and�Serbian Academy of Sciences and Arts, Belgrade, Serbia

Purpose: Homocysteine, together with its reactive thioester homocyste-ine thiolactone is proven risk factor for numerous CNS disorders includ-ing epilepsy. The aim of this study was to determine the effects ofchronic aerobic exercise on rat model of homocysteine – thiolactone –induced seizures.

Method: Adult male Wistar rats were familiarized with the treadmillapparatus (NeuroSciLaBG-Treadmill, Elunit, Serbia) for 3 days in ses-sions of 10 min at ramp belt velocity of 5–10 m/min. Afterwards, ratswere randomly divided into 2 groups: chronic aerobic exercise (30 mintreadmill training at 20 m/min velocity for 30 days) and sedentary control(the same time spent in treadmill apparatus at 0 m/min for the same per-

iod). At the end of training period, convulsive dose of homocysteine thio-lactone (8.0 mmol/kg) was intraperitoneally injected to rats from bothgroups and convulsive behavior was assessed by seizure incidence,latency to first seizure, number of seizure episodes and its severity (0–4grades scale).

Result: There were no statistically significant differences in seizureincidence induced by homocysteine thiolactone between exercised andsedentary rats (p > 0.05). Latency to first seizure was increased in exer-cised comparing to sedentary group of rats. Exercised rats displayedlower number of seizure episodes per rat in comparison with sedentaryrats (p < 0.05), but severity of these seizures did not differ significantlybetween groups.

Conclusion: These results indicate beneficial effects of chronic aerobicexercise in model of homocysteine thiolactone-induced seizures in rats,supporting the promotion of sport and physical exercise among patientswith epilepsy.

p356EARLY AND LATE MRI CHANGES IN RAT BRAINAFTER STATUS EPILEPTICUS AND BEHAVIORALIMPAIRMENTE. Suleymanova*, M. Gulyaev�, A. Barkova�, andN. Chepurnova�

*Lomonosov Moscow State University, Faculty of Biology,Moscow, Russian Federation; �Lomonosov Moscow StateUniversity, Moscow, Russian Federation; and �LomonosovMoscow State University, Biological faculty, Moscow, RussianFederation

Purpose: Status epilepticus is a dangerous condition which can lead tobrain damage and impairment of memory and cognitive functions later inlife. The purpose of our study was to investigate the relationship betweenacute damage caused by prolonged seizures and later consequences ofstatus epilepticus.

Method: The lithium-pilocarpine model of status epilepticus (SE) in ratswas used. MRI study of rat brain was performed 2, 7 and 30 days afterSE. High-resolution T2 images and T2-maps were obtained, and totaldamaged area, hippocampal volume, and T2 relaxation time in severalbrain structures were calculated. After the MRI study, animals weretested in an open field. The test was performed three times with 24-hourintervals. To study depression-like behavior in rats, forced swim test andtaste preference test were performed to evaluate depression.

Result: Two days after SE, an increase of T2 signal was found in hippo-campus and associated structures. The patterns of brain damage in ratsafter SE varied considerably. All rats after SE demonstrated hyperactivityin an open field one month later and did not habituate. These rats alsowere more active in the forced swim test, however some animals demon-strated the lack of taste preference. Rats with considerable acute changesin brain, tended to demonstrate higher activity in an open field in compar-ison with rats with less pronounced early MRI changes and were moreprone to anhedonia.

Conclusion: Rats with severe MRI abnormalities in brain found twodays after SE tend to develop more pronounced behavioral impairment 1month later.

p357BRIEF SEIZURES INDUCE A SEVERE ISCHEMIC/HYP-OXIC EPISODEG. C. Teskey, and J. S. FarrellUniversity of Calgary, Calgary, Canada

Purpose: Ischemic/hypoxic episodes and seizures both result in anumber of deleterious effects to brain functioning including enhanced

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inflammatory responses, blood brain barrier permeability, astrocyte acti-vation and neuronal death. This suggested to us that seizures may resultin an ischemic/hypoxic episode. We tested this hypothesis by measuringlocal brain oxygen levels, before during and after brief seizures in a num-ber of forebrain structures.

Method: Adults rats had both an electrode and an oxygen sensing op-trode implanted in their motor neocortex, amygdala or hippocampus.One week after implantation surgery, oxygen levels were recorded inawake, freely moving rats during and following electrically elicited sei-zures or other types of patterned electrical stimulation that did not resultin seizures.

Result: Immediately following termination of the afterdischarges weobserved a severe hypoxic episode (<10 mm pO2) that lasted on the orderof tens of minutes in the neocortex and an hour in the hippocampus. Elec-trical stimulation that did not give rise to a seizure did not result in a hyp-oxic episode. Pharmacological agents that did not affect the seizure butenhanced vasodilation and blocked vasoconstriction prevented the sei-zure-induced severe ischemic/hypoxic episode (SISIHE).

Conclusion: Seizures result in vasoconstriction that leads to reducedlocal blood flow and severely reduced oxygen levels. It is possible that itis not the seizures per se that directly cause the long-term disruption ofbrain function, but the resulting ischemic/hypoxic episode. This phenom-enon has potentially important implications for the management of sei-zure disorders.

p358THE DYNAMICS OF CORTICO-THALAMO-CORTICALNETWORK INTERACTIONS AT THE TRANSITION TOSPIKE-WAVE DISCHARGESG. Van Luijtelaar, and A. LuttjohannRadboud University Nijmegen, Nijmegen, The Netherlands

Purpose: Generalized absence seizures are generated within the cortico-thalamo-cortical system. We analysed thalamic and cortical-thalamicinteractions via multisite local-field-potentials with the aid of non-linearassociation analyses.

Method: WAG/Rij rats with multiple electrodes targeting subgranularlayers of the somatosensory-cortex, rostral and caudal RTN, VPM, ante-rior-(ATN) and posterior (Po) thalamic nucleus were used. Dynamics ofassociation strength, coupling-direction and time-delays between allchannel pairs were analyzed pre-ictally, ictally and in control periods.

Result: Earliest and strongest increases in coupling-strength were seenbetween cortical layer 5/6 and Po. Other thalamic nuclei becameinvolved later in SWD activity. The cortex guided most thalamic nucleiwhile cortex and Po kept a bidirectional crosstalk during the first 500 msof SWDs. Most thalamic nuclei guided the Po until the end of the SWD.While the rostral RTN showed increased coupling with Po, the caudalRTN decoupled. Instead, it directed its activity to the rostral RTN.

Conclusion: Next to the focal cortical instignation zone of SWDs, thePo seems crucial for their occurrence. This nucleus shows early increasesin coupling and is the only nucleus which responds to the cortex withinthe first 500 ms of SWDs. Other thalamic nuclei seem to have only afunction in SWD maintenance. Rostral and caudal-RTN have oppositeroles in the occurrence of SWD.

p359AGE-DEPENDENT CHANGES IN XCT AND EAAC1EXPRESSION IN SOMATOSENSORY CORTEX OFWAG/RIJ RATSJ. Van Liefferinge*, A. Schallier*, G. Van Luijtelaar�,Y. Michotte*, A. Massie*, and I. Smolders**Vrije Universiteit Brussel, Brussels, Belgium; and �RadboudUniversity Nijmegen, Nijmegen, Netherlands

Purpose: Oxidative stress is known to decrease convulsion thresholdand depletion of endogenous antioxidants was suggested to providea molecular mechanism that triggers ictogenesis in a genetic mousemodel for secondary generalized seizures (Takaki et al. Brain Res2008;1228:1–5). We therefore investigated total glutathione (GSH)content in somatosensory cortex (SSC) of pre- and symptomaticWAG/Rij rats, a well-validated model for absence seizures. More-over, protein expression levels of xCT (specific subunit of the cys-tine/glutamate antiporter) as well as EAAC1 were measured in theserats. These transporters provide respectively glial cells and neuronswith cyst(e)ine, the rate-limiting building block in the synthesis ofGSH.

Method: Semi-quantitative western blotting was performed on SSC tis-sue of respectively presymptomatic and symptomatic WAG/Rij animalsand age-matched ACI control rats using rabbit EAAC1 antibody (1:4000;Alpha Diagnostic) and rabbit xCT antibody (1:10000; Massie et al. Neu-roreport 2008;19:1589–1592.). Total GSH content was examined using aQuant-iT Protein Assay Kit (Invitrogen).

Result: A significantly decreased expression of xCT (ACI 100,0 €5,8%; WAG/Rij 73,5 € 5,8%; p = 0,03) and EAAC1 (ACI 100,0 €15,1%; WAG/Rij 53,7 € 2,5%; p = 0,002) was observed in the youngWAG/Rij rats. In the symptomatic WAG/Rij rats, protein levels of xCT(ACI 83,9 € 2,0%; WAG/Rij 161,4 € 28,9%; p = 0,002) were signifi-cantly increased compared to the age-matched ACI rats. Total GSH con-tent was unaffected in presymptomatic WAG/Rij rats.

Conclusion: Although expression levels of xCT and EAAC1 werealtered in SSC samples of both presymptomatic and symptomaticWAG/Rij rats, total GSH content was unaffected compared to ACIcontrol rats.

p360EVALUATION OF NOVEL BEHAVIOURAL CORRE-LATES TO ELECTROGRAPHIC SEIZURE ACTIVITY INMICEJ. Zelano, and K. KullanderUppsala University, Uppsala, Sweden

Purpose: Epileptic vulnerability in rodents is frequently evaluated byobserving the effects of a seizure-inducing insult, such as pilocarpineinjection. However, seizure scoring is difficult, user dependent, andrequires an elaborate setup. Lately, several new simplified ways of grad-ing seizure response have emerged in the litterature. The correlationbetween these behavioural observations and EEG-verified seizure activ-ity has not been investigated. This pilot study aimed to use video-EEG toevaluate novel simplified behavioural seizure correlates such as latencyto grade 5–6 seizure, number of grade 5–6 seizures, or seizure index (anarbitrary grouping of high-grade seizures), in the pilocarpine-induced sta-tus epilepticus model in mice.

Method: Video-EEG was performed on mice from the 129-strain,which is commonly used for genetic modification. Pilocarpine wasadministered as a single peritoneal injection and the animals wereobserved for 90 minutes. EEG and video was then interpreted sepa-rately and statistical correlation sought between behavioural correlatesand EEG seizure activity.

Result: Similar number of grade 5–6 seizures were observed in micewith very different duration of electrographic seizure activity. Latency tothe first grade 5–6 seizure correlated best with duration of EEG seizureactivity, but did not reach statistical significance.

Conclusion: Some of the novel behavioral correlates may not be optimalsurrogate markers for electrographic seizure activity, indicating that EEGshould ideally be performed when screening transgenic mice in thismodel. We plan a larger study to asess which behavioural correlate is bestto use in the absence of EEG.

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p361EFFECT OF LOW-FREQUENCY STIMULATION ONTHE AFTERDISCHARGE INDUCED BY ACUTE KIND-LING OF THE RABBIT HIPPOCAMPUSK. Tsuchiya, S. Kogure, A. Kusahara, and T. IwataSoka University, Hachioji, Tokyo, Japan

Purpose: We have performed fast Fourier transformation (FFT) analysison the afterdischarge (AD) induced by chronic hippocampal kindling ofthe rabbit and revealed that enhancement of the higher frequency band(HFB: 12–30 Hz) component is associated with kindled stage. In the pres-ent study, we examined effect of low-frequency stimulation (LFS) onADs induced by acute kindling of the rabbit hippocampus to reveal theunderlying mechanism of anti-kindling effect of LFS.

Method: Fourteen adult rabbits were used. Under deeply anesthesia,kindling stimulations (1 msec, biphasic 50 Hz, 1 sec train) with supra-threshold intensity for AD were delivered at 20-min intervals to the righthippocampus. The LFS was added at 1 Hz for 15 min immediately or 20sec after the kindling stimulation to the ipsilateral or contralateral sidewhen HFB in AD increased to the kindled level. FFT analysis on eachAD was performed to reveal the LFS effect.

Result: During the acute kindling, the power spectral density (PSD)ratio of HFB component against total PSD changed from 16.1 € 9.7%(mean€SD) at the initial stage to 45.9 € 17.6% (p < 0.001) at the finalstage. Both types of LFS application could not suppress the enhancementof HFB component, but suppress the appearance of kindling-inducedspontaneous seizure activity.

Conclusions: An enhancement of HFB component also occurred in theacute kindling. Anti-kindling effect of LFS may depend on stimulationsite and timing.

Epilepsy Surgery 3Tuesday, 02 October 2012

p362LOCALIZING VALUE OF ICTAL SPECT IN PATIENTSWITH TUBEROUS SCLEROSIS COMPLEX ANDINTRACTABLE EPILEPSYA. Jahodova*, M. Kudr*, P. Krsek*, V. Komarek*, P. Jayakar�,C. Dunoyer�, T. Resnick�, and M. Duchowny�

*University Hospital Motol, Prague, Czech Republic; and �

Brain Institute, Miami children hospital, Miami, FL, USA

Purpose: To assess a practical value of ictal SPECT in localizing the sei-zure onset zone in pediatric patients with tuberous sclerosis complex(TSC) and intractable epilepsy.

Method: We visually evaluated 52 ictal SPECT studies in 26 childrenwith TSC surgically treated in Miami Children's Hospital between 1994and 2010. The extent and location of the ictal hyperperfusion was evalu-ated and completeness of its surgical removal was assessed. The extent ofthe hyperperfusion zone resection was classified as ‘‘completelyresected’’, ‘‘partially resected’’ and ‘‘non-resected’’ and correlated withpostsurgical seizure outcomes. Outcomes were regarded as ‘‘favourable’’in patients with ‡90% seizure reduction and ‘‘unfavourable’’ in subjectswith <90% seizure reduction.

Result: There were 35 studies in previously non-operated patients, ninepostsurgical studies in patients who subsequently underwent a reopera-tion and eight postsurgical studies in patients who had no further surgery(excluded from outcome analyses). Cortical hyperperfusion was presentin 41(79%) ictal studies and absent in 11(21%) studies. In 41 positiveSPECT studies, 10(24%) were well-localized, 13(32%) lobar, 11(27%)

multilobar, 2(5%) hemispheric and 5(12%) bilateral. Favorable seizureoutcomes were achieved in 6/6 (100%) patients with completely resected,8/23(35%) with partially resected, 5/7(71.5%) with non-resected hyper-perfusion zone and in 1/8(12.5%) subjects with no ictal SPECT activa-tion.

Conclusion: Complete resection of the ictal SPECT hyperperfusionzone is a strong predictor of surgical success in children with TSC. Epi-lepsy surgery planning in TSC is nevertheless highly complex; SPECTfindings should be correlated with clinical, electrophysiological andother neuroimaging data. Supported by Kontakt Program ME09042, IGANT/11443-5, CZ.2.16/3.1.00/24022 and GAUK 17010.

p363EFFICACY OF VAGUS NERVE STIMULATION IN 28CONSECUTIVE PATIENTS WITH TREATMENT RESIS-TANT EPILEPSY NOT ELIGIBLE FOR EPILEPSY SUR-GERYF. Dainese*, G. Randazzo�, G. Pauletto�, F. Paladin*,C. Lettieri�, C. Conti§, M. Skrap�, L. Comelli�, A. Volzone�, andP. Bonanni�

*SS Giovanni e Paolo Hospital, Venice, Italy; �IRCCS EugenioMedea, Conegliano (TV), Italy; �SM della MisericordiaHospital, Udine, Italy; and §Dell’Angelo Hospital, Mestre (VE),Italy

Purpose: The aim of this study was to assess the efficacy and safety ofvagus nerve stimulation (VNS) in a consecutive series of patients withrefractory epilepsy (RE) not eligible for epilepsy surgery.

Method: This is a retrospective study of 28 patients who underwentVNS implantation for RE between 1996 and 2011. Patients wererecruited from 3 epilepsy units in the North-East of Italy. The age at timeof implantation was from 8 to 59 years (mean age 32,34; SD 12,7 y). Allpatients were classified according to the epileptic phenotype and the eti-ology. Twenty-one patients had focal or multifocal epilepsy, of whom 7with bitemporal epilepsy, 4 had Lennox-Gastaut syndrome, 2 had Dravetsyndrome, 1 had Angelman syndrome. According to the last proposal ofclassification, the etiology was structural in 16 patients, genetic in 3 andunknown in 9. All patients had a long duration of epilepsy before implan-tation (mean age 24 y).

Result: Duration of VNS treatment varied from 0 to 15 years (mean 3y). Mean seizure frequency significantly improved following implanta-tion in 64% of patients. Interestingly 56% of patients showed alsoimprovement in quality of life. No important side effects were reportedby patients.

Conclusion: VNS is a safe and effective palliative treatment option forRE not eligible for epilepsy surgery. Interestingly our data show thatVNS is an effective treatment not only in cases of epilepsy with structuralor unknown etiology but also in case of epilepsy due to a specific geneticcause as Dravet Syndrome and Angelman Syndrome.

p364RESECTIVE SURGERY FOR REFRACTORY STRUC-TURAL EPILEPSY IN INFANTS AND YOUNG CHIL-DRENG. Ramantani*, N. E. Fritz�, K. Strobl�, G. Wiegand§,S. Schubert-Bast�, H. Mayer�, R. Korinthenberg*, U. Stephani§,J. Zentner*, A. Schulze-Bonhage*, and T. Bast�

*University Hospital Freiburg, Freiburg, Germany; �UniversityChildren¢s Hospital, Heidelberg, Germany; �Epilepsy CenterKork, Kehl-Kork, Germany; and §University Medical CentreSchleswig-Holstein, Kiel, Germany

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Purpose: Resective surgery is becoming an important treatment optionfor refractory structural epilepsy in early childhood. We report on indica-tions, complications and outcomes in very young children undergoingepilepsy surgery at the Epilepsy Centre Freiburg.

Method: We retrospectively reviewed the electroclinical, neuroimagingand neurodevelopmental findings, surgical procedures and complica-tions, histologically defined epilepsy substrates and outcomes of childrenunder 3 years of age that underwent epilepsy surgery in the years 2001–2011.

Result: 30 children were included in this study. Seizure onset was in thefirst year of life in 28 (93%) patients and mean age at first surgery was20.6 months (5–33.6 months). 18 (60%) infants had a historyof infantilespasms. Epilepsy substrates consisted in malformations of cortical devel-opment in 24 (80%) cases, glioneural tumor alone or in combination withcortical dysplasia in 3 (10%), and infarct in 3 (10%). 34 surgical proce-dures were performed including 16 (47%) functional hemispherectomies,7 (21%) multilobar resections and 11 (32%) intralobar resections. 3 chil-dren underwent repeat surgery in our institution, while a single child hadthree consecutive resections. No mortalities occurred. Surgical complica-tions included hydrocephalus in 3 patients as well as meningitis and hem-orrhage in single cases. In follow-up from 1 to 11 years, seizure freedomwas achieved in 23 (77%) children (Engel I), while 5 (17%) demonstrateda worthwhile improvement (Engel II or III) and 2 (7%) children showedno remarkable improvement. Developmental outcomes were generallypreserved.

Conclusion: Benefit in terms of seizure control and developmental pro-gress is achievable in the majority of very young children with structuralepilepsy selected for resective surgery. While early complication ratesare infrequent and manageable, late complications are limited to exten-sive, hemispheric procedures. Cognitive outcomes were not compro-mised in the majority of our cohort.

p365CLINICAL FEATURES OF SEIZURES SEMIOLOGYAND ELECTROENCEPHALOGRAPHY IN YOUNGCHILDREN WITH LESIONAL TEMPORAL LOBE EPI-LEPSYX. Shao, and Z. SunBeijing Tiantan Hospital Affiliated to Capital MedicalUniversity, Beijing, China

Purpose: This study is to discuss the features of seizure semiolgy andelectroencephalography(EEG) in young children with lesional temporallobe epilepsy.

Method: 11 children with temporal lobe lesions were received presurgi-cal evaluation for intractable epilepsy. The age of seizure onset was under3 years. All patients were seizure-free after temporal lobectomy withmore than 1 year follow-up. We reviewed medical history and video-EEG monitoring to analyze semiology of seizures and EEG findings andcompared to that of adult TLE.

Result: All patients have daily seizures although with anti-epilepticdrugs (AEDs). 84 seizures were recorded and analyzed in 11 children(aged from 23 months to 108 months; mean 50.5 months). The age of sei-zure onset was from 1 month to 26 months (mean; 17.6 months). Allpatients exhibited prominent motor manifestations, including epilepticspasm, tonic seizure(symmtric or asymmtric) and unilateral clonic sei-zure. seven children manifested behavioral arrest similar to automotorseizures in adult TLE, but with shorter duration and more frequency.Automatisms were mostly orofacial and mannual automatism is rarelyobserved. EEG recording revealed that generalized discharges patternswere more common in younger children while focal or unilateral patternsusually in older children. All children have mental development delay orregression but with significant improvement after surgery, especiallywith early operation.

Conclusion: Lesional TLE in young children may present as a cata-strophic epilepsy. Although with generalized clinical and electrographicfeatures, a resective epilepsy surgery should be considered as early aspossible to achieve seizure control and improvement of mental develop-ment.

p366LONG-TERM OUTCOME OF RESECTIVE SURGICALPROCEDURES IN ADULT PATIENTS WITH REFRAC-TORY EPILEPSY-THE KORK SERIESA. M. Staack*, A. Wendling*, I. Wisniewski*, J. Scholly*,S. Bilic*, C. Kurth*, U. Kraus*, J. Saar*, B. Oehl�,D. Altenm�ller�, T. M. Freiman�, A. Schulze-Bonhage�,J. Zentner�, G. Reinshagen*, and B. J. Steinhoff**Kork Epilepsy Centre, Kork, Germany; and �Epilepsy Centre,University of Freiburg, Freiburg, Germany

Purpose: Epilepsy surgery is an established treatment option for a welldefined and pre-selected group of patients with drug-resistant epilepsy.The long-term follow-up is important to identify predictive factors for afavourable outcome.

Method: We collected data for 340 adult patients from the Kork Epi-lepsy Centre who had undergone surgery for drug-resistant epilepsy. Weused a standardized questionnaire to obtain updated information aboutpostsurgical outcome and classified seizure outcome according to theILAE surgery outcome scale (OC 1 – OC 6).

Result: In total 211 (62%) patients have been completely seizure free(OC1), 228 (67%) patients have remained seizure free, apart from simplepartial seizures (OC2) at the time of the most recent evaluation. Meanpost-operative follow-up time was 6.7 years (range 1.0–21.6 years). Arunning-down phenomenon (initially seizures and finally completeremission) has been seen in 38 (11.2%) patients. The majority of patients(266; 78.2%) underwent temporal lobe resections. 64% of the temporalresected patients and 52% of the patients with extra-temporal resectionsbecame seizure-free (OC1). Only 38% of the patients with negative MRIachieved complete seizure-freedom (OC1).

Conclusion: With 62% (OC1) to 67% (OC2) seizure-free patients, ourstudy shows satisfying long-term outcome results over more than sixyears. In our study, best results were seen in lesional temporal lobe epi-lepsy, whereas MRI-negative epilepsy was associated with a less favour-able outcome in line with the literature.

p367RISK FACTORS FOR EPILEPTIC SEIZURE OF CAV-ERNOUS MALFORMATIONS IN THE CENTRAL NER-VOUS SYSTEM: 52 CASESC. Huang*, J. Li�, and D. Zhou�

*Sichuan University, Chengdu, China; and �West ChinaHospital, Chengdu, China

Purpose: To determine the risk factors for preoperative and postopera-tive epileptic seizure in patients with cavernous malformations (CMs).

Method: We retrospective studied 52 consecutive patients diagnosedwith CMs who were surgically treated and histopathologically confirmedin West China Hospital of Sichuan University from January 2009 to June2001. Clinical data, treatment procedure and follow-up information werecollected.

Result: In the univariate analysis, factors associated with preoperativeepileptic seizure were low birth weight (p = 0.017), temporal lobeinvolvement (p = 0.003) and cortical lesion (p = 0.025). In the multivari-

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ate analysis, the cortical lesion showed a high risk for preoperative epi-leptic seizure (OR=10.48; 95% CI 1.61–68.23). In the univariate analy-sis, patients with temporal lobe CMs were found more likely to be seizurefree after surgery (p = 0.016). The maximum diameter of CMs longerthan 2.5 cm (p = 0.012) and disease course longer than 1 year (p =0.050)predicates an unfavorable outcome. In the multivariate analysis,temporal lobe involvement still showed a favorable outcome (OR=0.038;95% CI 0.002–0.833). Application of ECoG did not make significant dif-ference to seizure outcome (p = 0.430).

Conclusion: Surgical treatment of patient with CMs is satisfactory inmost cases and temporal lobe involvement usually predict favorablepostoperative seizure outcome whether under the monitoring of ECoGor not. Thus, epileptic patients with CMs should be considered for sur-gical treatment especially when cortical brain layer or temporal lobewas involved.

p368SHORT-TERM RESULTS OF STEREOTACTIC ANTE-RIOR CALLOSOTOMY IN THE TREATMENT DRUGRESISTANT EPILEPSYK. Kostiantyn, V. Tsymbaliuk, Y. Medvedev, Y. Zinkevich,A. Popov, S. Dichko, and O. KanaykinInstitute of Neurosurgery, Kyiv, Ukraine

Purpose: The purpose of study is to evaluate seizure outcome in patientswith intractable primary and secondarily generalized epilepsy whounderwent stereotactic anterior corpus callosotomy.

Method: Eight patients aged 4–28 years with drug-resistant epilepsyunderwent stereotactic anterior callosotomy, among them were 6 chil-dren. 5 pts had daily seizures and all 8 pts had episodes of status epilepti-cus in their history. 4 pts had partial seizures with secondarilygeneralization and one patient had primary generalized seizures. 7 ptshad symptomatic epilepsy and 1 pt – cryptogenic.

Result: In postoperative follow up 4 – 22 months (mean – 12 months) 1pt became seizure free, in 4 cases achieved 90% and in other 3 cases –50% or greater seizures reduction respectively. In1 case seizure fre-quency did not change significantly. There were no postoperative com-plications in our series.

Conclusion: Our short-term study confirms that stereotactic anteriorcallosotomy is a safe palliative surgical procedure that is suitable forsome patients with drug-resistant epilepsy, suffering from primary or sec-ondarily generalized seizures who are not candidates for focal resectivesurgery.

p369ACUTE INTRALESIONAL RECORDING IN HYPOTHA-LAMIC HAMARTOMAS: DESCRIPTION OF 4 CASESN. Specchio*, M. Rizzi�, L. Fusco*, A. Medda*, S. Cappelletti*,C. Marras*, F. Vigevano*, and O. Delalande**Bambino Ges� Children's Hospital, Rome, Italy; and �

Neurological Institute ‘‘C. Besta’’, Milan, Italy

Purpose: To report the results of acute intralesional recording of the in-terictal activity arising inside the Hypothalamic hamartomas (HH) in 4cases and to compare it with concurrent scalp EEG.

Method: We have reviewed the medical records of 17 children affectedby drug resistant focal epilepsy associated to HH, referred between Janu-ary 1990 and December 2011 to the Neurology Division of the BambinoGes� Children's Hospital in Rome, and ‘‘Carlo Besta’’ Neurological Insti-tute in Milan.

All clinical notes were reviewed in order to evaluate the age at onset,the seizure type at onset and during the follow-up, treatment and epilepsyoutcome. HH were defined according to the classification proposed byDelalande et al (Delalande et al., 2003).

In 4 out of 17 studied patients an intraoperative endoscopic intrale-sional recording was performed. In 3 cases intraoperative stereo-EEGwas carried out using foramen ovale electrodes (Dixi Medical ACS-798S, 5 contacts), and DBS leads in 1 case (Medtronic 3389, 4 contacts).Scalp-EEG was performed in all patients (referential montage, lackingfrontal and central leads for surgical reasons).

Result: In 10 out of 17 cases a surgical approach was performed: 4 ofthem underwent a one stage stereo-endoscopic disconnection, 3 cases adouble stage stereo-endoscopic disconnection, and 1 case required a mul-tistage stage stereo-endoscopic disconnection. One patient performed abilateral deep brain stimulation (DBS) protocol, 1 a surgical resection, 1radiotherapy, and 1 radiosurgery.

Following Delalande classification HH were mostly of type 2 (8 out of17), followed by type 3 (6 out of 17) and lastly type 4 (3 out of 17). Nocases were classified as type 1.

Data on intraoperative stereo-EEGAll patients (4 cases) presentedgelastic seizures, associated to focal with secondarily generalization. Sei-zures frequency ranged from multiple per day to multiple per week. Sei-zure duration was between few seconds to 60 seconds. FollowingDelalande classification 2 patients had type 2 HH and other two had type4 HH. Interictal scalp EEG showed epileptiform abnormalities in allpatients, in 2 cases they were evident on temporal region, in one overbilateral parieto occipital, and in one over central and parietal regions.

In all patients intraoperative scalp-EEG showed synchronous interic-tal epileptic discharges which were recorded from the same side of thelesion. From the depth electrode high amplitude fast activity in sequencesof variable duration was recorded.

In all cases the predominant side of the EEG abnormalities was ipsilat-eral to the activity recorded within the hamartoma.

Conclusion: We detected the electrical activity of the lesion, and com-pared it with the scalp-EEG activity recorded in the same time. Our dataconfirm the epileptogenicity of HH. Clinical and neurophysiologicalfindings in all described cases suggest that the cortical activation is sec-ondary to the epileptogenic activity of HH. Intraoperative electrographicrecording may be considered as part of a strategy of trans-endoscopic sur-gery for HHs.

p370VAGUS NERVE STIMULATION DECREASE EMER-GENCY ASSISTANCE AND HOSPITALIZATION INDRUG-RESSISTANT EPILEPTIC PATIENST. Garc�a-Sobrino, X. Rodr�guez-Osorio, A. L�pez-Ferreiro,M. Santamar�a-Cadavid, E. Corredera, A. Prieto, M. Peleteiro,and F. J. L�pez-Gonz�lezComplejo Hospital Cl�nico Universitario de Santiago deCompostela, Santiago de Compostela, Spain

Purpose: VNS is an effective method to reduce seizure frequency inrefractory epilepsy when resective surgery is ruled out. We aim to studyefficacy and need of medical resources after VNS implantation in relationwith the preimplantation period.

Method: Restrospective study of patients with VNS implantation(2002–2011) with ‡1 year of follow-up. Response to VNS was achievedafter ‡ 50% of reduction of seizures. We analyzed demographic data,efficacy, emergency assistance, hospitalization days in relation with epi-lepsy and outpatient follow-up after one, two and three years postimplan-tation, compared with 1 previous year period.

Result: Thirthy-nine patients (57.5% females) with a median age of 41[31,52] years old were studied. Median frequency of seizures per monthwas 25 [6.25,144.5], with a time of evolution of epilepsy of 26 [18,37]

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years. Response to VNS after 1, 2 and 3 years was achieved in 47.37% (n= 39), 51.6% (n = 38) and 54.84% (n = 32) of patients. After VNS, med-ian emergency assistance due to epilepsy was 0[0,0], 0[0,1] and 0[0,0.5],reduced in comparison with the preimplantation period 1 [0,1] (p =0.002; p = 0.027; p = 0.062), with a median of hospitalization days of0[0,0] at 1, 2 and 3 years, compared to pre-VNS period 0 [0,2] (p = 0.025;p = 0.007; p = 0.05). However, attendance to the epilepsy clinic did notshow significant reduction after VNS implantation with a median of4[2,7], 5[3,7] and 4[3,5] annual visits compared to the year before VNS 5[4,6] (p = 0.108; p = 0.462; p = 0.085).

Conclusion: VNS is effective and reduces the need for emergency assis-tance and days of hospitalization in refractory epileptic patients.

p371EVOLUTION UP TO 18 YEARS AFTER SURGERY FORTEMPORAL EPILEPSY WITH HIPPOCAMPAL SCLE-ROSIS: IMPACT OF TECHNIQUE, MEDICATION MAN-AGEMENT AND PRESURGICAL VARIABLESD. Crestani*, M. Hemb*, R. F. Severino�, A. Palmini*,E. Paglioli*, E. Paglioli*, J. Costa Da Costa*, M. Portuguez*,N. Azambuja*, and M. Nunes**Hospital Sao Lucas, Porto Alegre, Brazil; and �Sao LucasHospital, Porto Alegre, Brazil

Purpose: The chances of remaining seizure free for long periods are stillunclear for patients undergoing surgery for mesial temporal lobe epilepsyand unilateral hippocampal sclerosis (MTLE/HS). Likewise, the impactof practical variables such as surgical technique and post-operativereduction of medication needs clarification.

Method: We followed 108 patients with unilateral MTLE/HS for 8 to18 years and generated Kaplan-Maier survival curves for the probabil-ity of remaining seizure free and for the modulating effect of medic-aton and surgical technique. Univariate and multivariate regressionanalyses were perfomed to determine the impact of these and othervariables.

Result: A history of generalized tonic clonic seizures (GTCS) waspresent in 10% of the patients and only 16% needed intracranial EEG.The probability of remaining completely seizure-free at 12 and 18 yearswas 65% and 62%. 75% of patients have discontinued or significantlyreduced antiepileptic drugs (AEDs). The type of surgical technique didnot impact. Multivariate analysis showed that both a history of GTCSand remaining on full or almost full doses of AEDs significantly dimin-ished the probability of remaining seizure free (Cox regression: p =0.003 CI: 1.84–22.41 for GTCS; p = 0.048, CI: 0.07–5.27 for AED man-agement).

Conclusion: Patient selection may be the most important determinant ofremaining seizure free over the years. When the epileptologic profileindicates more restricted disease, removal of neocortical structures doesnot lead to better chances of seizure control and the reduction or discon-tinuation of AED does not prevent favorable results.

Epilepsy Surgery 4Tuesday, 02 October 2012

p372EPILEPSY SURGERY IN THE UNITED KINGDOM IN2011, AN UPDATEA. Neligan*, J. K. Solomon*, B. Pettorini�, and W. F. Harkness�

*UK ILAE Chapter, London, UK; and �Societyof BritishNeurological Surgeons, London, UK

Purpose: Epilepsy surgery is increasingly recognised as an importantmodality of treatment for people with epilepsy and particularly for peoplewith medically refractory epilepsy. The last assessment of adult epilepsysurgery services was completed in 2000–1. We sought to provide an up todate picture of the state of adult and paediatric epilepsy surgical servicesin the UK.

Method: We obtained a list of SBNS representatives in all UK Neuro-surgical units. We wrote to the relevant consultants in the (17) identifiedepilepsy surgery centres across the country asking them to prospectivelycomplete a questionnaire detailing all epilepsy surgery carried out at theircentre between April 2010 and March 2011. The response rate was100%.

Result: In total there were 874 procedures (excluding invasive electroderecording) with the common resective procedure being temporal lobe sur-gery for hippocampal sclerosis (142 in adults, 13 in children). In contrastextra-temporal lesionectomies were far less common (78 adults, 18adults) while non-lesional extra-temporal lobe procedures were rare (24adults, 2 children). VNS implantation was carried in 401 people (276adults).

Conclusion: In comparison to the figures from ten years ago, there is noevidence that the number of adult temporal lobe resections carried outhas significantly changed in the intervening years. VNS implantation isthe most commonly performed procedure in both adults and children withthe numbers carried out in adults increasing. These figures suggest thatepilepsy surgery remains an under –utilised service with a large numberof people with refractory epilepsy not treated surgically.

p373LONG-TERM OUTCOME OF FUNCTIONAL TEMPO-RAL LOBE DISCONNECTION FOR NON-LESIONALMESIOTEMPORAL EPILEPSYB. Legros, N. Massager, P. Tugendhaft, C. Depondt, T. Coppens,L. Drogba, N. Benmebarek, O. De Witte, and P. Van BogaertULB-Hpital Erasme, Brussels, Belgium

Purpose: In refractory mesial temporal lobe epilepsy (MTLE), surgicaltreatment is used to obtain seizure freedom, generally through the ana-tomical removal of the mesial structures. We developed a technique offunctional disconnection of the temporal lobe (TLD). Here, we presentlong-term seizure outcome and complications of TLD in MTLE.

Method: Data of 45 patients operated on for intractable MTLE usingTLD were studied. Indication for TLD surgery was retained after a stan-dard preoperative evaluation of refractory epilepsy and using the samecriteria as for standard MTLE resection surgery. The epilepsy outcome of41 patients with minimum 1-year follow-up was analyzed. Morbidityoutcome was assessed on the whole population.

Result: Mean follow-up duration was 3.48 y (range 1–9.5 y). At last fol-low-up 27 patients (66%) were completely seizure-free. Actuarial out-come display a probability of being seizure-free after 5 years of 67.3%and after 9.5 years, of 44.9%. No patient died after surgery and no sub-dural hematoma or hygroma occurred. Neurological impairment aftersurgery included speech fluency deficit, hemiparesis, hemianopsia andoculomotor nerve palsy. Permanent hemiparesis occurred in 3 patients,hemianopsia in 5 patients and oculomotor paresis in 1 patient.

Conclusion: TLD is a valuable surgical technique for patients withintractable MTLE. The morbidity and long-term seizure outcome of TLDare similar to standard surgical removal techniques. This functional sur-gery could be an interesting alternative to resection that can reduce oper-ating time and risks for subdural collections after surgery.

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p374INFANTILE SPASMS AS THE UNIQUE SEIZURE TYPEIN HEMISPHERIC EPILEPSIES RELATED TO PERINA-TAL MIDDLE CEREBRAL ARTERY STROKE – OUT-COME FOLLOWING HEMISPHEROTOMYC. Bulteau, D. Taussig, M. Chipaux, M. Fohlen, G. Dorfmuller,S. Ferrand-Sorbets, and O. DelalandeFondation Rothschild, Paris, France

Purpose: Infantile spasms (IS) are specific of severe early epilepticencephalopathy. They can be the unique ictal manifestation in patientswith early ischemic lesions.

Method: We present 3 patients out of our series of 215 hemispheroto-mies performed between 1990 and 2009, who presented with IS withoutfocal seizures related to perinatal stroke in the distribution of the middlecerebral artery. Interictal as well as ictal video-EEGs were retrospec-tively studied. We considered postoperative follow-up.

Result: Seizure onset was between 5 and 7 months of age. Mean age atthe time of EEG-video recording was 22 months, and 27 months at thetime of surgery. All patients had hemiparesis; a psychomotor regressionoccurred after onset of the IS. Interictal EEG favoured unilateral epilepsywith lack of physiological activity over the damaged hemisphere andmultifocal sharp waves, whereas physiological activity was recordedover the safe hemisphere. In two cases, sharp waves were also recordedsynchronously over both hemispheres. During the spasms, asymmetrywas clinically and/or electrically obvious. No other seizure type was dis-closed. Follow-up ranged between 26 and 144 months; all three patientsare seizure-free without medication. The two patients who underwentearly hemispherotomy acquired normal verbal intelligence, whereas thethird, operated on at 38 months of age, remained with severe mental retar-dation.

Conclusion: Isolated IS can be a presentation of hemispheric epilepsyrelated to a post-ischemic lesion. Efficiency of hemispherotomy to con-trol seizures is very high and can prevent mental retardation. Predictivefactors for a favourable post-operative development remain to be studied.

p375LONG-TERM OUTCOME AFTER MULTILOBAR EPI-LEPSY SURGERYD. Altenm�ller*, T. Bast�, S. Schubert-Bast�, K. Strobl§,G. Wiegand–, T. M. Freiman**, and J. Zentner***Epilepsy Center, University Hospital Freiburg, Freiburg,Germany; �Kork Epilepsy Centre, Kork, Germany; �UniversityChildren's Hospital, Heidelberg, Germany; §Epilepsy CenterKork, Kork, Germany; –University Medical Centre Schleswig-Holstein, Kiel, Germany; and **University Hospital Freiburg,Freiburg, Germany

Purpose: In patients with pharmacoresistant (multi-)focal epilepsy,multilobar surgery might be required if the epileptogenic area cannot belocalized within a single lobe. We analyzed the pre- and postoperativefindings of patients in whom a multilobectomy (MLE) was performed.

Method: The data of all patients who underwent MLE at the EpilepsyCenter Freiburg between 2001 and 2010 were retrospectively reviewed.

Result: 18 patients (median age at MLE 71 months; median follow-up31 months) fulfilled inclusion criteria. 10 patients received resection oftwo lobes (1 temporo-parietal; 3 parieto-occipital; 6 temporo-occipital).In 8 patients, resection of 3 lobes (all temporo-parieto-occipital) was per-formed, often after failure of more circumscribed previous surgical pro-cedures. 11 patients (61%) gained seizure freedom, which mostly wasaccompanied by developmental progress and EEG recordings withoutepileptiform potentials after surgery. 3 patients (17%) did not experience

any relevant benefit with regard to seizure outcome. As expected, postop-erative hemianopia was found in all patients. In single cases, an ischemiaof the basal ganglia, an infarction of the lateral thalamus or a bleeding inthe postcentral region with (transient) motor or sensory deficit wasobserved. According to MRI criteria, in 10 patients (55%) completeresection or disconnection of the presumed epileptogenic lesion wasachieved by MLE. In 14 patients (78%), histopathology revealed focalcortical dysplasia. 3 patients subsequently underwent hemispherotomy,which led to seizure freedom.

Conclusion: MLE based on a thorough presurgical epilepsy evaluationcan be a successful treatment option with acceptable risks, particularly inchildren with widespread dysplastic lesions.

p376OUTCOME OF EXTRA TEMPORAL EPILEPSY SUR-GERY AND HEMISPHERECTOMYD. D. Ruikar, S. Jayalakshmi, M. Surath, M. Panigrahi, andR. VarmaKrishna Institute of Medical Sciences, Secunderabad, India

Purpose: To assess the outcome of surgery in patients with medicallyrefractory extra-temporal epilepsy (ETLE) and hemisperectomy patientsevaluated with a non invasive protocol and to determine the predictors ofoutcome following surgery.

Method: Retrospective analysis of pre-surgical (ictal EEG, MRI, fMRI,SPECT, PET, neuro-psychology) surgical and post surgery data was per-formed in 48 patients who underwent surgery for ETLE and 14 patientsfollowing hemispherectomy and who had at least one year post surgeryfollow up. Outcome was assessed according to Engel's outcome classifi-cation. Stepwise multiple logistic regression analysis was employed indata analysis.

Result: Mean follow up was 32 months; 36(60%) were males. Intra-operative electro-corticography was done in 42 and cortical stimulationin 23 and neuronavigation in 6. Frontal resections were the commonest(28), followed by parietal resections. The pathology showed cortical dys-plasia in 21, gliosis in 8 and low grade tumoral lesions in 10. Transientpost surgery complications occurred in 3. Functional hemispherotomywas performed in 6 and vertical parasagittal hemispherectomy in 8.Hemispherical atrophy due to childhhood insult was the etiology in 6,hemispherical dysplasia in 5 and Rassmussen's encephalitis in 3. At lastfollow up seizure free outcome was noted in 37(77%) with ETLE and9(75%) after functional hemispherectomy. After stepwise multiple logis-tic regression analysis, the variables found to be significant (P=<05) andpredicting favourable outcome were normal IQ and absence of acute postoperative seizures.

Conclusion: Favourable outcome after epilepsy surgery can be obtainedin patients with ETLE and hemispherectomy after evaluation with non-invasive protocol if presurgical evaluation is carefully planned.

p377SEIZURE OUTCOME AFTER HEMISPHERECTOMY –DATA FROM THE SWEDISH NATIONAL EPILEPSYSURGERY REGISTERI. Olsson*, A. Edelvik�, R. Flink�, B. Rydenhag�, andK. Malmgren§

*Institute of Clinical Sciences, Gothenburg, Sweden;�Sahlgrenska Academy, University of Gothenburg, Gothenburg,Sweden; �Uppsala Akademiska Hospital, Uppsala, Sweden; and§Sahlgrenska Academy at Gothenburg University, Gçteborg,Sweden

Purpose: To present data from a population-based series of hemispher-ectomies.

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Method: The Swedish National Epilepsy Surgery Register, whichincludes data on all epilepsy surgery procedures in Sweden since 1990(completely prospective since 1995), was analysed for hemispherecto-mies 1995-June 2010. The outcome two years after surgery is presented.Twenty-three patients were identified, 12 males and 11 females. Themedian age at epilepsy onset was four months (range zero to 11 years).Preoperatively 19/23 (83%) had more than 50 seizures per month, 52%more than 100/month. The mean number of antiepileptic drugs (AEDs)was 2.3 (range 1–5). The side of operation was right in ten cases and leftin 13. The median age at hemispherectomy was five years and threemonths (range six months to 20 years seven months).

Result: The aetiology was developmental in 16 cases (12 with malfor-mations of cortical development, four with hemimegalencephaly),acquired in four and progressive in one (Rasmussen). There were nomajor complications. Thirteen were seizure-free at the two-year follow-up (57%), three had more than 75% reduction in seizure frequency. Tenout of sixteen (63%) with developmental aetiology became seizure-free.Six out of the 13 seizure-free patients were off medication, the meannumber of AEDs was 1.1 (range 0–3).

Conclusion: The seizure outcomes in this population-based series ofhemispherectomies were well in accordance with results of larger series.However, we had more patients with developmental aetiology than isusually reported, with equally good results, and most of the patients couldstop or reduce medication, within two years after surgery.

p378THE CONTRIBUTIONS OF MEG IN SURGICAL DECI-SION MAKING OF LESIONAL EPILEPSYJ. P. Blount*, C. B. Smith�, R. C. Knowlton�, H. Kim�, M. Goyal�

, C. J. Rozzelle*, P. Kankirawatana�, and K. O. Riley�

*Children's of Alabama/University of Alabama at Birmingham,Birmingham, USA; and �University of Alabama at Birmingham,Birmingham, USA

Purpose: Lesional epilepsy has traditionally referred to cases of tumorsor vascular cavernous malformation that are readily visualized on MRIscans. However as the quality of imaging has improved other substrateshave become increasingly defined as MRI evident lesions that are epilep-togenic. The approach to such lesions remains controversial and incom-pletely understood. Resection of the lesion is straightforward andefficient yet may fail to control seizures in up to 40% of cases. Whetherthe lesion or peri-lesional tissue is primarily epileptogenic remains uncer-tain. The necessary extent of pre-operative evaluation and operativeresection of peri-lesional tissue varies between experienced centers andremains controversial. We reviewed a large contemporary surgical seriesof lesional epilepsy to address the contribution of magnetoencephalogra-phy (MEG/MSI) studies to localization of lesional epilepsy.

Method: A 10 year (2001–2011) retrospective review of a 2 institution(University of Alabama at Birmingham/Childrens Hospital of Alabama)experience was undertaken after IRB approval. Among 320 patientsoperated for lesional epilepsy a seizure occurrence rate of greater than orequal to two seizures was confirmed in 122 (44 adults, 78 Pediatric)patients. These were identified who had epilepsy, an abnormal pre-opera-tive vEEG and a pre-operative MRI that revealed a lesion in the region ofEEG abnormality. Lesions were broadly interpreted and included tumors(n = 46), FCD (n = 38), encephalomalacia from infarcts (n = 13), cavern-ous malformations (n = 6) and lesions associated with the phakamotoses(n = 10). Histopathologic confirmation was attained in all cases. MEGwas utilized in 50 cases (9 tumors, 19 FCD, 1 cavernoma, 22 other).

Result: The seizure freedom rate for pure lesionectomy was 81% fortumors with complete resection and 61% if residual disease wasobserved. Lesionectomy in FCD resulted in 50% class I outcome. MEGcontributed to surgical localization by demonstrating dipoles both withinthe lesion and extending beyond the lesion into the peri-lesional tissue.Engel class I outcomes were seen n 77% of MEG directed lesionectomies

and in 77% of pure lesionectomies (P = 1.0, CI=95%). Thus there was nota significant improvement in outcome when MEG was incorporated butwe found MEG to impact surgical approach and decision making in 60%of tumor cases.

Conclusion: MEG contributes to surgical decision making in lesionalepilepsy. Extra-operative utilization includes conventional localizationof diploles to localize ictal onset, localization of epileptogenesis beyondthe lesion and by allowing study of tissue that is difficult to study withother functional imaging modalities. Intra-operative utilization includesfusion with frameless navigation systems allowing guidance of IC-EEGelectrode placement with greater accuracy. Outcome is not directlyimpacted by MEG incorporation but surgical approach often is.

p379COMPARATIVE STUDY OF EFFICACY AND SAFETYBETWEEN RADIOSURGICAL CALLOSOTOMY ANDOPEN CALLOSOTOMY FOR LENNOX-GASTAUT SYN-DROME IN A THIRD-LEVEL NEUROLOGICAL CEN-TERJ. D. D. Del Castillo Calc�neo*, D. San Juan Orta*,M. A. Alonso Vanegas�, S. Moreno Jimenez*, and M. HerbasRocha�

*National Institute of Neurology and Neurosurgery, MexicoCity, Mexico; and �Instituto Nacional de Neurolog�a yNeurocirug�a Manuel Velasco Suarez, Mexico City, Mexico

Purpose: Determine & compare the effect of surgical corpus callosoto-my (SC) and radiosurgical corpus callosotomy (RC) in seizure frequencyreduction in Lennox-Gastaut Syndrome (LGS) and to stablish safety ofSC and RC in LGS.

Method: Retrospective analysis (2004–2012) of patients who under-went either RC or SC was performed. Clinical, neurophysiological, neu-roimaging and follow up variants were obtained and analyzed usingdescriptive statistics (means and standard deviations) as well as Student'sT test for independent samples.

Result: 33 subjects were included 21 [14 males] in SC and 12 [5 males]in RC. The average age at time of surgery was 20.6 € 7.9 years in RC and25 € 7.9 in SC. Average time to diagnosis was 2.4 € 2.5 y in RC and 2.1 €2.9 y in SC. All subjects were diagnosed with cryptogenic Lennox-Gas-taut Syndrome and multi-focal epileptic activity. To perform the surgeryin the RC group a mean dose of 43.2Gy (€4) were used. Follow-up wasperformed at 12 (€4) months. There was a decline in monthly seizure fre-quency for RC (-60%) as well as for SC (-55%) with no significant differ-ence between them (p = 0.64). Tonic and Atonic seizures were the mostreduced in both groups. In RC 6 subjects presented with complicationsrelated with severe cerebral edema. There were no complicationsreported on SC.

Conclusion: RC shows similar efficacy compared with surgical corpuscallosotomy in reducing seizure frequency in subjects with LGS. Eventhough there is a major incidence of complications in the RC group.

p380CORRELATION OF FDG-PET AND VOXEL-BASED MRIMORPHOMETRY WITH INVASIVE EEG FINDINGSAND SURGICAL RESULTS IN MRI-NEGATIVE EPI-LEPSYJ. Scholly*, A. M. Staack*, I. J. Namer�, U. Kraus*, S. Bilic*,K. Strobl*, T. Bast*, M. P. Valenti-Hirsch�, P. Kehrli�,E. Hirsch�, A. Schulze-Bonhage§, J. Zentner§, andB. J. Steinhoff*

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*Kork Epilepsy Centre, Kork, Germany; �University RegionalHospital Centre of Strasbourg, Strasbourg, France; �StrasbourgUniversity Hospital, Strasbourg, France; and §Epilepsy Centre,University of Freiburg, Freiburg, Germany

Purpose: Conventional MRI fails to identify the lesion in about a quar-ter of patients with surgically remediable epilepsy. In MRI negative sur-gical candidates we investigated the localizing value of FDG-PET,voxel-based morphometric MRI analysis (VBM) and scalp video-EEGand correlated the findings with the epileptogenic zone defined by inva-sive EEG and histological findings after surgery.

Method: 20 MRI-negative patients were prospectively investigated.Scalp video-EEG recordings, the visual analysis of FDG-PET overlaidonto a 3D-set of the patient's anatomic MRI scans as well as VBM MRIanalysis based on algorithms of the statistical parametric mapping soft-ware (SPM5) were performed. 14 patients underwent invasive EEG, 12were operated.

Result: The epileptogenic zone defined by invasive EEG was tempo-ral in three, temporal plus in two and extratemporal in nine cases,confirming the electro-clinical hypothesis after scalp recording in allbut one case. The outcome was favorable (Engel class I) in tenpatients (83%). The histological examination revealed focal corticaldysplasia (FCD) in nine cases and other pathologies in the rest. Atopographic concordance with the epileptogenic zone could be dem-onstrated by FDG-PET in eight of nine FCD cases (89%). The VBMMRI analysis detected abnormalities suggesting FCD in six cases.Only two of them corresponded to the electro-clinical epileptogenicfocus and only one to a confirmed FCD.

Conclusion: Our data suggest a good localizing value of FDG-PETespecially in cases of MRI obscure FCD, whereas a VBM MRI analysisshowed low diagnostic sensitivity and specifity (11% and 33% respec-tively) in our series.

p381INTRACRANIAL EEG ICTAL ONSET FREQUENCY:HIGH OR LOW?J. Chung*, U. Maoz�, N. Tsuchiya�, O. Tudusciuc�, S. Ye�,A. Mamelak*, and D. Eliashiv**Cedars-Sinai Medical Center, Los Angeles, USA; �CaliforniaInstitute of Technology, Pasadena, USA; and �Riken Institute,Tokyo, Japan

Purpose: Identifying ictal onset frequencies with wide spectrum EEGfrequency analysis.

Method: Eight patients with medically refractory partial epilepsy under-going intracranial macroelectrode monitoring (4 depth electrodes, 4 sub-dural grids) were analyzed. Digital EEG data was sampled at 2 kHz atvarious intervals. Multiband frequency and power analysis were per-formed to characterize the predominating frequency during the interictal,pre-ictal, ictal, and postictal periods.

Result: Thirty-one seizures—14 seizures collected from subdural gridand 17 from depth electrodes—were analyzed. In each of the 18 seizuresfrom six patients, the ictal onset was localized to one contact and wascharacterized by a significant increase of 10 – 30 Hz frequencies preced-ing the increase of 30 – 100 Hz frequencies by 3 seconds before propaga-tion. Focal surgical resections were performed in the areas correlated tothe synchronization of these alpha-beta range frequencies and HFO priorto and during the patients’ clinical seizures. These six patients have sei-zure-free outcomes confirming the localization of seizure onset. On thecontrary, 13 seizures from two patients did not demonstrate the synchro-nization of alpha-beta range frequencies, and the patients did not achieveseizure freedom post-operatively.

Conclusion: Previous studies of HFO from intracranial microelectrodesand/or single neuron recordings consistently showed the frequencies atictal onset above 100 Hz. In our study, HFO were preceded by lower fre-quency activity, and the presence of the lower frequencies synchroniza-tion correlated with post-operative seizure freedom. HFO may not be thefirst ictal manifestation in some cases, and the lower range ictal frequen-cies should not be overlooked. Larger studies are underway.

Medical Therapy and Pharmacology 4Tuesday, 02 October 2012

p382STATUS DYSTONICUS IN A CASE OF WILSON'S DIS-EASEO. Cokar, A. Mutlu, F. F. Ozer, M. Gurbuz, H. Acar, and F. GencHaseki Educational and Research Hospital, Istanbul, Turkey

Purpose: Dystonia is a movement disorder characterized by sustainedmuscle contractions producing torsional and repetitive movements orabnormal postures. Status dystonicus is a generalized, intense and poten-tially fatal exacerbation of muscle contractures which is necessitatedurgent hospital admission. It mainly affects patients with primary or sec-ondary dystonia and is often triggered by fever, infection, trauma, sur-gery, abrupt introduction, withdrawal or change in medical treatment.We report one case of Wilson's disease presented with dystonic status.

Method: A 49 year-old male with a previous diagnosis of Wilson's Dis-ease treated trientine and zinc sulfate presented with generalized tonicclonic seizure. At time of admission he had hyperthermia up to 39 ordm;C. After control of seizure with diazepam and levetiracetam infusions thepatient presented severe episodes of dystonia involved face and left armand leg. Elevated serum creatine phosphokinase level was documented.Symptoms were resistant to conventional medication.

Result: Gabapentin 900 mg/day, brought significant improvement andthe patient remained clinically stable.

Conclusion: Although status dystonicus is a rare but serious condition,prompt diagnosis is needed and gabapentin can be used to control severeepisodes of dystonia.

p383EARLY TREATMENT WITH LACOSAMIDE: RESULTSOF RELACOVA STUDYM. Garc�s*, E. L�pez Gomariz�, P. Giner�, N. Torres§, E. Noe–,J. L�pez-Trigo**, C. Santafe��, R. MuÇoz��, M. Bonet§§, andV. Villanueva**Hospital Universitario y Polit�cnico La Fe, Valencia, Spain;�Hospital Luis Alcanyis, Xativa, X�tiva, Spain; �HospitalUniverssitario Dr. Peset, Valencia, Spain; §Hospital Dr. Peset,Valencia, Spain; –Hospital Valencia al MAr, Valencia, Spain;**Consorcio Hospital General Universitario Valencia,Valencia, Spain; ��Hospital Clinico Universitario Valencia,Valencia, Spain; ��Hospital de La Ribera, Alzira, Spain; and§§Hospital Arnau de Vilanova, Valencia, Spain

Purpose: To analyze early use of lacosamide (LCM) in RELACOVAstudy, a large multicenter prospective collection of patients on LCM inclinical practice.

Method: Consecutive patients with partial epilepsy where LCMwas used as 1st, 2nd or 3rd antiepileptic drug (AED) (monotherapy or

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combination) and at least a follow-up of 3 months were studied. Theinformation was obtained at baseline, 3, 6 and 12 months. Efficacy andadverse events (AE) were analysed. Concomitant AEDs and number ofprior AEDs were also evaluated.

Result: Fifty-six patients were included. Forty-nine patients were fol-lowed for 6 months and 40 patients for one year. Six patients had triednone AEDs, 20 patients one AED and 30 patients 2 AEDs. None patientswithdrew before 3 months, retention rate at 6 months was 91.8% and at12 months was 82.5%. Seizure free patients were 37.5%, 32.7% and37.5% at 3, 6 and 12 months. Responders were 64.3%, 71.4% and 70% at3, 6 and 12 months. No significant differences were observed accordingto the number of prior AEDs although a trend to a better responseappeared when LCM was used as 1st or 2nd drug. Better response wasobserved when LCM was used with a non-sodium channel blocker (SCB(-)) (responder rate at 3 months showed p 0.033). AE were reported by26.8%, 34.7% and 35% of patients at 3, 6 and 12 months. No differenceswere observed according to concomitant drugs.

Conclusion: Efficacy of LCM in partial epilepsy is high when used earlyand seems to be better when used with SCB (-).

p384ON THE USE OF INTRA RECTAL VALIUM INPATIENTS WITH DRAVET SYNDROME: FAMILIESOPINIONN. Coqu�*, N. Chemaly�, and R. Nabbout�

*Alliance Syndrome de Dravet, Brest Cedex 2, France; and�Hpital Necker Enfants Malades, Paris, France

Purpose: Intra rectal Diazepam (DZ) remains the first rescue medica-tion for acute prolonged convulsive seizures in children. In this study, weaimed at assessing the experience of the families of patients presentingDravet syndrome (DS) concerning DZ use.

Method: We invited 53 families of patients with DS to complete anauto-administered on-line questionnaire. Questions addressed the differ-ent aspects of intra rectal DZ use: usual administrators, and time, easi-ness, and risk of errors in the preparation and administration. Parentswere questioned about their feeling concerning efficacy, usefulness inemergency setting, facility of its administration, and possible refuse ofcare givers to use it.

Result: 52 families answered the questionnaire. DZ was usually admin-istered by mothers and less frequently by other care givers. Almost allparents (92%) agreed on its efficacy. However, 50% found that prepara-tion and administration are affected by errors especially when carried outof the parents’ presence. Many educational and non-medical institutionsrefused to use DZ.

Conclusion: Parents confirm the efficacy of intra rectal DZ and empha-sized the need for a medication that is easier to prepare and administer.

p385A RETROSPECTIVE OBSERVATIONAL STUDY OFTHE USE, EFFECTIVENESS, TOLERABILITY, ANDRETENTION OF CARBAMAZEPINE AND VALPROATEIN CHILDREN AND YOUNG PEOPLEN. P. Docheva, and W. P. WhitehouseUniversity of Nottingham, Nottingham, UK

Purpose: In 2006, ILAE criticised the lack of primary evidence for theuse of Carbamazepine (CBZ) and Sodium Valproate (VPA) in the treat-ment of epilepsies in children and young people. This is a single centre,retrospective, registered clinical audit of process and outcome to assessthe use, efficacy, tolerability, and retention of CBZ and VPA.

Method: Children under 18 years of age, starting VPA or CBZ 01/11/07–31/10/10 were ascertained using the hospital pharmacy database.Paper and electronic patient records were reviewed and data capturedusing a standard proforma. Simple descriptive statistics, Chi-squared,logistic regression and Kaplan-Meyer survival plots in SPSS (v19) wereused.

Result: 84 children (Males 45) aged 0–17 years (median 8.0) wereidentified, 44/84 had CBZ, 40/84 VPA, and 13/84 both. In 61/84(73%) this was their 1st antiepileptic drug (AED). 30/44 (68%) onCBZ had focal epilepsies and 28/40 (70%) on VPA had generalizedepilepsies. The audit comprised 29 person years of CBZ exposure, and34 for VPA. 37/44 (84%) of patients on CBZ had >50% seizure reduc-tion, including 13/44 (30%) seizure free. 36/40 (90%) on VPA had>50% seizure reduction, including 12/40 (30%) seizure free. 48/84(57%) experienced adverse events, none serious, 7/44 (16%) on CBZhad increased seizures, 3/44 (7%) had rash; 6/40 (15%) on VPA com-plained of excessive weight gain.

Conclusion: The audit of outcome showed CBZ and VPA to be effectivefirst line AEDs, however we caution the use of CBZ as a first line AEDbecause of the risk of seizure aggravation.

p386BUCCAL PYRIDOXINE: RESCUE MEDICATION FORPROLONGED SEIZURES IN CHILDREN WITH PYRI-DOXINE DEPENDENT EPILEPSY, IN THE COMMU-NITY SETTINGL. Christodoulou*, and S. Beri�

*St Mary's Hospital NHS Trust, London, UK; and �St Mary'sHospital, London, London, UK

Purpose: Pyridoxine dependent epilepsy (PDE) is a rare autosomalrecessive disorder, characterized by early-onset, drug-resistant seizures,responsive only to pharmacological doses of pyridoxine. Mutations in theALDH7A1 gene, which encodes the protein antiquitin, have beendescribed. Buccal midazolam is now the standard treatment for pro-longed seizures in children with epilepsy, in the community setting. Wereport two siblings from a consanguineous family of Asian origin withPDE, responding only to buccal pyridoxine for prolonged seizures.

Method: A 4-year-old boy, developed multifocal seizures in the neona-tal age, not responsive to standard anticonvulsants but responding to pyri-doxine. Serum Pipecholic acid was high. Homozygous mutation inALDH7A1 gene confirmed the diagnosis of PDE. Currently seizures arerelatively well controlled on oral Pyridoxine. He does get intermittent,prolonged, generalized tonic-clonic seizures with infectious illness.Repeated doses of buccal midazolam and rectal diazepam have failed tocontrol seizures in the community setting. Buccal pyridoxine has beenextremely effective in stopping these seizures and preventing admissionsto hospital. His 12-year-old sister was diagnosed with PDE, after hisdiagnosis became apparent. She has spastic quadriplegia with drug resis-tant multifocal epilepsy, currently well controlled on oral pyridoxine andOxcarbazepine. Breakthrough prolonged seizures have failed to respondto benzodiazepines and only respond to buccal pyridoxine.

Result: Not applicable.

Conclusion: Buccal pyridoxine may have a role as rescue medication incontrolling breakthrough seizures in children with PDE and should beconsidered as a therapeutic option in the community setting.

p387COGNITIVE EFFECTS OF LACOSAMIDED. Ijff, M. Majoie, and A. AldenkampKempenhaeghe, Heeze, Netherlands

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Purpose: Lacosamide is a novel antiepileptic drug (AED) with potentialbenefit as adjunctive treatment in patients with partial-onset seizures.1–3

The cognitive effects have, as yet, not been studied. In this open clinicalprospective study the cognitive effects of Lacosamide (VIMPAT) whenused as adjunctive antiepileptic therapy in adolescent and adult patientswith epilepsy was evaluated.

Method: We included 33 patients (24 females, 9 males) aged between16–74 years (mean 37 years sd:14.5). All patients suffered from focal epi-lepsy: 42% had cryptogenic and 58% had symptomatic epilepsy. Patientswere using LCS treatment with a daily dose of between 100 to 600 mg(mean daily dose of 298.2 mg/day). Mean follow-up time was 7 months(range 1–24). Patients were treated with up to four concomitant AEDs(mean: 1.9). Subjective complaints were evaluated using the SIDAED;effects on cognition were evaluated using the CVST, a test measuringspeed of central information processing.

Result: On the CVST a significant faster reaction time was found at thesecond evaluation (p=.010). On the SIDAED (subjective list of 46-itemswith possible AED-related complaints), patient complained more abouttheir cognitive function at the second evaluation (p=.002).

Conclusion: Lacosamide has a positive effect on the information pro-cessing speed although patients complained more, especially about theircognitive function. Possible explanations for this discrepancy are theeffect of reduction of co-medication and increased worries of patientsduring a trial, causing overestimation of cognitive effects.

p388STEADY-STATE PHARMACOKINETICS AND TOLER-ABILITY OF ESLICARBAZEPINE ACETATE AND OX-CARBAZEPINE IN HEALTHY VOLUNTEERSA. Falc¼o*, M. Vaz-Da-Silva�, T. Nunes�, L. Almeida§, andP. Soares-Da-Silva�

*4Health Consulting, Cantanhede, Portugal; �University ofPorto, Porto, Portugal; �BIAL – Portela & Ca. SA, S¼o Mamededo Coronado, Portugal; and §University of Aveiro, Aveiro,Portugal

Purpose: To investigate the steady-state pharmacokinetics and assessthe tolerability of once-daily (QD) regimen of eslicarbazepine acetate(ESL) and twice-daily (BID) regimen of oxcarbazepine (Trileptal�;OXC) in healthy volunteers.

Method: Single centre, open-label, randomised, three-way crossoverstudy in 12 healthy volunteers. The study consisted of two 8-daytreatment periods separated by a washout period of 10–15 days. Ineach treatment period the volunteers received either a daily oral doseof ESL 900 mg QD or ESL 450 mg BID (data not shown) or OXC450 mg BID.

Result: Eslicarbazepine was the major drug entity in plasma, accountingfor 93.0% and 82.2% of total exposure with ESL 900 mg QD and OXC450 mg BID, respectively. Eslicarbazepine Cmax (lmol/L) was 82%higher following ESL QD (87.34) compared to OXC BID (47.96). Theratio eslicarbazepine exposure(mmol*h/L)/dose(mmol) was 0.3733(1133.71/3037.25) and 0.2695 (961.35/3567.60) for ESL and OXC,respectively, which translates in a 39% increase in efficiency of ESL ver-sus OXC to deliver eslicarbazepine. ESL was 19% more efficient thanOXC to deliver all active moieties. The extent of exposure to drug entitiesR-licarbazepine and oxcarbazepine was approximately 4-fold higherwith OXC as compared with ESL. 30 and 18 treatment-emergent adverseevents were reported in the OXC 450 mg BID group and the ESL 900 mgQD group, respectively.

Conclusion: In comparison to OXC, administration of ESL resulted in39% more eslicarbazepine, less R-licarbazepine and less oxcarbazepine,which may correlate with the tolerability profile reported with ESL.

p389LONG-TERM EFFICACY AND TOLERABILITY OFZONISAMIDE AS ADJUNCTIVE THERAPY INPATIENTS WITH REFRACTORY PARTIAL EPILEPSYA. La Neve*, N. Pietrafusa*, G. Pontrelli*, T. Francavilla*,V. Durante*, M. Ladogana*, T. Lisi*, and G. Boero�

*Policlinico di Bari, Bari, Italy; and �SS. Annunziata Hospital,Taranto, Italy

Purpose: To assess long-term efficacy and tolerability of zonisamide(ZNS) as add-on treatment in patients with refractory partial epilepsy.

Method: prospective, open label study conducted in 69 patients withrefractory partial epilepsy. The study included 3 periods: Baseline (3months); drug titration (> 2 months) to ZNS 300 mg/day; Observa-tion, during which the ZNS could be increased up to the maximumtolerated dose. Inclusion criteria were: age >16 years, diagnosis offocal epilepsy, pharmacoresistance to at least 2 adequate previousantiepileptic drugs, stable concomitant antiepileptic therapy for 3months during baseline. Exclusion criteria were: systemic or progres-sive neurological diseases, poor compliance, history of pseudo-sei-zures, pregnancy. Efficacy was evaluated comparing mean monthlyseizures frequency during last three months of observation to base-line seizures frequency; statistical analysis was made using Poissonmodels for count data.

Result: mean number of antiepileptic drugs before ZNS was 5.5 € 2.5;mean duration of follow-up was 19.5 months. 59 patients were includedin the efficacy analysis and statistically significant reduction of the meanmonthly seizures frequency was found at 12 months (19.14 € 38.60 vs.9.73 € 18.10, p = 0.004) and at 24 months (19.14 € 38.60 vs. 8.86 €17.51, p = 0.008). 24 patients (34%) complained adverse events wich ledto drug discontinuation.

Conclusion: Our data suggest good efficacy and a good tolerabilityof ZNS in the long term, especially considering the severe pharma-coresistance of our patients and the drug administration in polythera-py regimen.

p390THE EFFECTS OF ESLICARBAZEPINE ON RECEP-TORS, ION CHANNELS, ENZYMES AND TRANSPORT-ERSA. I. Loureiro*, M. J. Bonif�cio*, L. Wright*, and P. Soares-Da-Silva�

*BIAL – Portela & Ca. SA, S¼o Mamede do Coronado,Portugal; and �University of Porto, Porto, Portugal

Purpose: This study was aimed to determine the interaction of es-licarbazepine, the main active metabolite of eslicarbazepine acetate, withpotential biological targets.

Method: Displacement of binding of specific ligands or substrates for95 human G-protein coupled and ligand gated receptors, ion channels,enzymes and transporters was tested in the presence of 400 lM es-licarbazepine. Some eletrophysiological experiments were conductedwith mouse N1E-115 cells and transfected cells expressing humanCav3.2 channels.

Result: In the presence of 400 lM eslicarbazepine, no relevant interac-tions were observed with receptors (acetylcholine, adenosine, adrenergic,angiotensin II, cannabinoid, cholecystokinin, dopamine, GABA, gluta-mate, histamine, melatonin, neurokinin, neurpeptide Y, neurotensin, opi-oid, purine, serotonin, somatostatin and TRH), ion channels (type Ncalcium, GABA chloride, potassium ATP-sensitive and Ca2 + -activated),enzymes (acetylcholine esterase, acetylcholine transferase, carbonic

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anhydrase I and II, glutamic acid decarboxylase, COX-2, MAO-A andMAO-B, caspases [1–10], kinases [CK1d, Fyn, GSK3b, MAPK1,MAPK3, PKA, PKCb2, PHCz, ROCK2, SGK1] and nitric oxide syn-thase) and transporters (dopamine, noradrenaline, serotonin and GABA).Eslicarbazepine does not alter fast inactivation of voltage-gated sodiumchannel (VGSC), but reduced VGSC availability through enhancementof slow inactivation with an affinity to the slow inactivated state 5.9 timeshigher than to the channels in the resting state. Eslicarbazepine inhibitedhigh and low affinity CaV3.2 inward currents with IC50`s of 0.4 and 62.6lM, respectively.

Conclusion: Eslicarbazepine is a selective slow inactivator of VGSCand potent Cav3.2 blocker devoid of effects upon major G proteincoupled and ligand gated receptors, ion channels, enzymes andtransporters.

p391A CASE REPORT OF THE SAFE USE OF LEVETIRACE-TAM IN A PATIENT WITH SICKLE CELL DISEASEA. Nitkunan, and T. Von OertzenSt George's Hospital, London, UK

Purpose: Levetiracetam is an anti-epileptic which is metabolised pri-marily in blood cells by enzymatic hydrolysis. The use of levetiracetamhas not been reported in patients with sickle cell disease. Such patientswith abnormal red blood cells may have difficulties metabolising leveti-racetam. We report the use of levetiracetam in a patient with sickle celldisease.

Method: A 22 year old Nigerian gentleman with sickle cell disease(homozygous SS) suffered from childhood bilateral strokes resulting insecondary generalised seizures that have been refractory to treatment. Hehas severe learning difficulties, spastic quadriplegia (uses a wheelchair),no speech and needs assistance with all activities of daily living. He hastried multiple anti-epileptic drugs and a ketogenic diet to no avail. Hewas started on levetiracetam during an episode of status epilepticus aged20. He has now been on levetiracetam for just over 2 years and is cur-rently on a dose of 1 g twice a day.

Result: His seizures have remained refractory and he is on polytherapy.Although difficult to assess because of polytherapy, he has not sufferedfrom any obvious side effects. Trough levetiracetam level was 19.1 (nor-mal range (10–37). In the 2 years prior to starting levetiracetam, heneeded 21 units of blood to manage his anaemia. In the 2 years since start-ing levetiracetam, he has needed 7.

Conclusion: This case illustrates that levetiracetam is not only safelytolerated in this patient with sickle cell anaemia but also that levetirace-tam has not adversely affect his sickle cell disease.

p392DRUG UTILIZATION STUDY WITH LACOSAMIDE INDAILY CLINICAL PRACTICE IN BELGIUM: ANINTERIM ANALYSISW. Van Paesschen*, H. Hauman�, B. Legros�, M. De Backer§, E.Webster–, and P. Dedeken§

*University Hospital Gasthuisberg, Lueven, Belgium; �GeneralHospital St. Maarten, Duffel, Belgium; �ULB Erasme Hospital,Brossels, Belgium; §UCB Pharma, Brussels, Belgium; and–UCB Pharma, Raleigh, USA

Purpose: Lacosamide was approved in 2010 for reimbursement in Bel-gium as add-on therapy for patients (‡16 years) with uncontrolled focal

epilepsy after failure of at least 3 lifetime antiepileptic drugs. This studyis being conducted to document patient demographics, lacosamide dos-ing, evolution of seizure control, and tolerability during a 6-month periodin a real-life setting.

Method: Patients were either already being treated (Group 1) or initiatedtreatment with lacosamide at enrollment (Group 2). Seizure control wasdetermined by investigators using a 4-category scale (much improved,improved, stable, worsened), and tolerability by spontaneous patient-reported treatment-related adverse events (AEs).

Result: At interim analysis, 51 patients (28 female, age 17–77 years) of150 had completed an observational period of at least 4.5 months or haddropped out. Patients were highly refractory; all had ‡3 lifetime AEDsand 35% had ‡7. Following a mean study duration of 162 days, the meandaily lacosamide dose in Groups 1 and 2 was 347 and 297 mg (range150–600 mg), respectively. On study completion, seizure control wasimproved or much improved in 53% of patients in Group 1 and in 56% ofGroup 2. AEs occurred in 29% of patients (most frequently fatigue, dizzi-ness or vertigo). Thirteen patients discontinued (29% of completers, 10%of enrolled) due to AEs (n = 8) or lack of efficacy (n = 5); 2 were lost tofollow-up.

Conclusion: Conclusion Data from this study so far suggest that in rou-tine clinical practice, lacosamide is well tolerated and improves seizurecontrol in highly refractory patients. Sponsored by UCB Pharma.


p393A RETROSPECTIVE OBSERVATIONAL STUDY OFCOMPARATIVE LACOSAMIDE COST IN A REALWORLD SETTING IN THE USA (VOYCE)S. Janssens*, H. Benhaddi*, T. Durgin�, and S. Borghs�

*UCB Pharma, Brussels, Belgium; and �UCB Pharma SA,Smyrna, GA, USA

Purpose: To compare the changes in treatment cost after lacosamide isadded to monotherapy, versus after another antiepileptic drug (AED) isadded, in patients with epilepsy in clinical practice.

Method: This was a retrospective, observational, 1-to-n matched-cohorts study on a US claims database (SDI). The observation period was6 months, both pre- and post-index. Index was defined as the date whenlacosamide or one of eight other AEDs (controls) was added to existingtherapy, which in this report consisted of AED monotherapy. Costs of in-and outpatient visits, and medication for epilepsy and non-epilepsy, werecollected from the database. The percentage in average change from pre-to post-index was calculated.

Result: From pre- to post-index, total treatment cost decreased by23.2% when lacosamide (n = 410) was added to monotherapy and by5.5% with controls (n = 1908). Cost of inpatient visits decreased in bothgroups (96.5% with lacosamide versus 78.7% with controls), as did costof epilepsy-related outpatient visits (26.4% versus 26.7%). Non-epi-lepsy-related outpatient visit cost remained stable with lacosamide(0.9%), but increased with controls (22.8%). AED medication costincreased by 153.8% with lacosamide and 66.1% with controls. Cost fornon-AED medication increased in both groups; by 23.2% with lacosa-mide compared with 37.5% with controls.

Conclusion: In clinical practice, adding lacosamide to monotherapyresulted in a greater decrease in total treatment cost compared with otherAEDs, despite the greater increase in AED medication cost. Further anal-yses, looking at adding to polytherapy, and in focal epilepsy patientsonly, are ongoing. Sponsored by UCB Pharma.

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p394HEPATOTOXICITY AND ANTICONVULSANT THER-APY IN CHILDREN AND ADOLESCENTSS. Karkelis, O. Papadaki-Papandreou, M. Lykogeorgou,M. Nikita, and G. ChrousosUniversity of Athens, Athens, Greece

Purpose: Epilepsy and sufficient epilepsy treatment is a challengingproblem for all clinicians taking care of children and adolescents. Theaim of the study was to investigate the impact of epilepsy treatment onliver function tests in children and adolescents.

Method: 287 children and adolescents(165 males, 122 females) epi-lepsy diagnosed during the last 5 years and aged 2 months-16 years wereenrolled. All patients medical files were reviewed in order to estimate:age of treatment initiation, type of treatment, number of seizures permonth, presence of status epilepticus and liver function tests using bloodsamples(ALT, AST, gGT, ALP, total bilirubin, direct bilirubin, total pro-tein, albumin) at baseline, 6 months and 12 months after treatment initia-tion. Abnormal baseline liver tests were found in 29 patients who wereexcluded. SPSS-19 statistical software and x2-test were used for data sta-tistical analysis.

Result: Abnormal liver function tests were found in 48 patients, autoim-mune hepatitis in 2 patients and acute liver failure in 1 patient. Statisticalsignificant correlation(p < 0,05) was found between the number of sei-zures, the duration of therapy and the number of anticonvulsant drugsused from the one hand, and the liver enzymes values from the otherhand: the higher the number of seizures and/or drugs used, the higher theliver enzymes values. The most hepatotoxic drugs were sodium valpro-ate, carbamazepine and phenobarbital.

Conclusion: Study results show very clearly that antiepileptic medica-tions can cause liver dysfunction in children and adolescents, but in mostcases this is a ‘tolerable’ side effect and also that significant hepatotoxic-ity is very rare.

p395ADVERSE EFFECTS OF AEDS ARE RELATED WITHDOSE AND NUMBER OF AEDS: OBSERVATIONALSTUDY WITH ADVERSE EVENT PROFILES. E. KimHaeundae Paik Hospital, Inje University, Busan, Korea

Purpose: Epilepsy surgery is available in selected patients, still themainstream of treatment of epilepsy is antiepileptics (AED). The adverseeffects (AE) of AEDs are major obstacle preventing maintenance of com-pliance and control of AE is important issue in clinical practice.

Method: We performed this study with a brief 19-item self-reportinstrument, the Adverse Events Profile (AEP). Two AEPs were screenedseparately with interval of at least 1 month. The inclusion criteria were 1)taking AEDs for at least 6 months, 2) no change of AED dosage between2 AEPs, 3) no adding on other medications between 2 AEPs, 4) at least80% of compliance between 2 AEPs. AED loads were calculated as thesum of prescribed daily dose (PDD)/defined daily dose (DDD) ratios foreach co-prescribed AED.

Result: 218 patients were eligible for this study. 121 patients were onmonotherapy and 97 patients were on polytherapy. The correlationbetween scores of 1st AEP (baseline) and 2nd AEP was excellent (Spear-man correlation coefficient= 0.82, p < 0.0001). AED loads was relatedwith the score of AEP?the score of AEP with over dose (>1 PDD/DDD)Vs with target dose (1 £ PDD/DDD), p = 0.006 by Mann-Whitney test?.Also, AEP scores were significantly different between patients withmonotherapy and patients with polytherapy ?the score of AEP withmonotherapy Vs polytherapy, p = 0.0002 by Mann-Whitney test?. In the2 AEDs combination, the score of AEP was marginally lower in the com-bination of 2 AEDs acting on sodium channel blocker with multiple

mechanisms than other combinations. However, age, duration of expo-sure to AEDs, or frequency of seizures between 2 AEPs were not relatedthe the score of AEP.

Conclusion: The AE are related with burden of AEDs and the number ofAEDs.

p396COMPARISON OF DRIED BLOOD SPOTS ANDPLASMA VALPROIC ACID AND CARBAMAZEPINELEVELSS. T. Kong*, W. H. Lim�, H. Y. Wang�, Y. L. Ng�, P. C. Ho*, andS. Lim�

*National University of Singapore, Singapore, Singapore;�Singapore General Hospital, Singapore, Singapore; and�Duke-National University of Singapore-Graduate MedicalSchool, Singapore, Singapore

Purpose: Gas chromatography mass spectrometry (GC-MS) has beenutilized for quantitative analyses of individual antiepileptic drugs(AEDs), one AED at a time but not simultaneously. To facilitate fastertherapeutic AED monitoring process by healthcare professionals forpatients with epilepsy (PWE), we (1) develop a GC-MS assay to concur-rently measure both Valproic Acid (VPA) and Carbamazepine (CBZ)levels using one dried blood spot (DBS), and (2) correlate DBS measuredVPA and CBZ levels with their plasma levels.

Method: 30 PWE taking VPA and CBZ concomitantly were recruited.One DBS, containing ~15 lL of blood, was acquired for the simultaneousmeasurement of both drug levels using GC-MS. Measured DBS levelswere correlated to therapeutic drug monitoring of plasma levels done atthe hospital laboratory. Analysis was done using Statistical Package forSocial Sciences (SPSS) version 19.

Result: DBS levels were well-correlated to plasma levels: r2 > 0.85 forVPA and r2 > 0.73 for CBZ. Percentage differences between plasma andDBS levels were found to be consistent, with the mean values of 58.2%(95%CI=55.35–61.14) for VPA and 3.1% (95%CI=-1.17–7.46) for CBZ.To calculate VPA plasma level, the conversion formula is 1.775 x (DBSVPA level) + 13.525. To calculate CBZ plasma level, the formula is0.692 x (DBS CBZ level) + 2.644.

Conclusion: The consistent correlation of DBS to plasma measureddrug levels could make DBS an alternative tool for monitoring clinicallevels of VPA and CBZ. Further study incorporating more patients andvalidation of the DBS assay are currently undergoing.

p397SERUM CONCENTRATIONS OF LACOSAMIDE INPATIENTS WITH EPILEPSY: INFLUENCES OF DOSE,AGE, GENDER AND COMEDICATIONS. Markoula*, R. Teotonio�, P. Patsalos�, and J. Duncan**Epilepsy Society, Chalfont St Peter, UK; �Hospitais daUniversidade de Coimbra, Coimbra, Portugal; and �UCLInstitute of Neurology, London, UK

Purpose: To investigate the influence of lacosamide doses, gender, ageand comedication on lacosamide serum concentrations in epilepsypatients.

Method: Lacosamide concentrations were measured in the TherapeuticDrug Monitoring Unit at The Chalfont Centre for Epilepsy. Daily dose,demographic data and comedication were recorded. Patients were furtherstratified in two groups according to the interval between last lacosamideadministration and blood collection (collection £2 h and ‡8 h after laco-samide administration or in 2–8 hours).

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Result: 299 patients (150 females) on lacosamide with a median age of41 (18–79) years and a median daily dose of 300 (50–600) mg were retro-spectively recruited. 123 patients took enzyme-inducing comedication.The mean lacosamide serum concentration was 28.5 € 16.4 lmol/l.27,4% of the patients presented toxic symptoms at a mean lacosamideconcentration of 29.6 € 15.4 lmol/L. This was independent of sodiumchannel acting comedication. Lacosamide concentrations were correlatedwith the dose and the intervals from dosing with no correlation with age.Women had higher concentrations (31.3 € 19.1 vs 25.6 € 12.6 lmol/L, p= 0.003) but not higher daily dose or percentage of toxic symptoms. Meanlacosamide concentrations were lower in patients taking enzyme-induc-ing comedication (21. 8 € 11.7 vs 33.8 € 18.6 lmol/L, p < 0,001). Aftermultivariate regression analysis with respect to daily dose and intervals,enzyme-inducing medication and gender were statistically significantlyrelated to serum concentrations.

Conclusion: Lacosamide concentrations are decreased by enzyme-inducing comedication. Higher concentrations in women could beexplained by lower body mass and the absence of higher frequency oftoxicity may imply a potentially higher female tolerance.

p398THE MTLE MOUSE AS A MODEL OF HUMAN TEMPO-RAL LOBE EPILEPSY: A COMPARATIVE STUDY OFTHE MOST COMMONLY-USED ANTIEPILEPTICDRUGSV. Duveau*, M. Langlois*, C. Bouyssieres*, T. Chabrol�,C. Dumont*, A. Depaulis�, and C. Roucard**SynapCell, La Tronche, France; and �Grenoble Institut desNeurosciences, Grenoble, France

Purpose: Mesiotemporal lobe epilepsy is one of the most prominentform of focal drug resistant epilepsy. A better understanding of mecha-nisms underlying this resistance would help to identify new active com-pounds. However, the need to have relevant models of MTLE hasemerged. Recently, morphological and electroclinical features of MTLEhas been observed in adult mice after unilateral injection of kainic acid inthe dorsal hippocampus. In this work, we investigated the effect of themost commonly used antiepileptic drugs (AEDs) on the occurrence offocal and spontaneous hippocampal paroxysmal discharges (HPD).

Method: Using the MTLE mouse model, we studied the dose responseeffect of commonly used AEDs, with acute or chronic administration pro-tocols, on the occurrence and the duration of HPD by deep EEG recording.

Result: Injection of classical AEDs (e.g. valproate and lamotrigine)failed to suppress HPD in a dose-dependent way. Indeed only high dosesare effective (400 and 90 mg/kg, respectively) and are associated withmodifications of the general behavior and/or EEG basal activity. A dose-dependent suppression of HPD was observed with some other AEDs: car-bamazepine, levetiracetam, vigabatrin, pregabalin, tiagabine and alsowith diazepam without noticeable behavioral or EEG side-effects.

Conclusion: Our data show that our MTLE mouse model display a phar-macological profile similar to the one observed in patients suffering fromrefractory MTLE. The MTLE mouse model therefore provides a criticaltool to find new treatments against epilepsy.

p399DRUG UTILIZATION STUDY WITH LACOSAMIDE INDAILY CLINICAL PRACTICE IN BELGIUM: ANINTERIM ANALYSISW. Van Paesschen*, H. Hauman�, B. Legros�, M. De Backer§,E. Webster–, and P. Dedeken§

*University Hospital Gasthuisberg, Lueven, Belgium; �GeneralHospital St. Maarten, Duffel, Belgium; �ULB Erasme Hospital,

Brossels, Belgium; §UCB Pharma, Brussels, Belgium; and–UCB Pharma, Raleigh, USA

Purpose: Lacosamide was approved in 2010 for reimbursement in Bel-gium as add-on therapy for patients (‡16 years) with uncontrolled focalepilepsy after failure of at least 3 lifetime antiepileptic drugs. This studyis being conducted to document patient demographics, lacosamide dos-ing, evolution of seizure control, and tolerability during a 6-month periodin a real-life setting.

Method: Patients were either already being treated (Group 1) or initiatedtreatment with lacosamide at enrollment (Group 2). Seizure control wasdetermined by investigators using a 4-category scale (much improved,improved, stable, worsened), and tolerability by spontaneous patient-reported treatment-related adverse events (AEs).

Result: At interim analysis, 51 patients (28 female, age 17–77 years) of150 had completed an observational period of at least 4.5 months or haddropped out. Patients were highly refractory; all had ‡3 lifetime AEDsand 35% had ‡7. Following a mean study duration of 162 days, the meandaily lacosamide dose in Groups 1 and 2 was 347 and 297 mg (range150–600 mg), respectively. On study completion, seizure control wasimproved or much improved in 53% of patients in Group 1 and in 56% ofGroup 2. AEs occurred in 29% of patients (most frequently fatigue, dizzi-ness or vertigo). Thirteen patients discontinued (29% of completers, 10%of enrolled) due to AEs (n = 8) or lack of efficacy (n = 5); 2 were lost tofollow-up.

Conclusion: Data from this study so far suggest that in routine clinicalpractice, lacosamide is well tolerated and improves seizure control inhighly refractory patients.

Sponsored by UCB Pharma.

p400EFFICACY OF PROGABIDE ADD-ON FOR REFRAC-TORY EPILEPSYX. Zou, T. Yuan, and B. WuWest China Hospital, Sichuan University, Chengdu, China

Purpose: Our objective is to evaluate the efficacy of progabide whenused as an add-on treatment for people with refractory epilepsy.

Method: We searched the Cochrane Epilepsy Group Specialized Regis-ter, the Cochrane Central Register of Controlled Trials, PubMed . Wealso contacted the manufacturers of progabide and researchers in thisaspect.

Result: A total of seven studies were included. For the whole studies,compared with placebo, progabide was more effective on refractory epi-lepsy (P < 0.01). The results of subgroup analysis showed that progabidewas no effective on refractory partial epilepsy (P > 0.05), and more effec-tive on refractory partial and generalized epilepsy (P < 0.01). Global clin-ical judgment OR, compared to placebo, was 14.42 (95% CI 3.68-56.58).

Conclusion: In people with refractory partial epilepsy, progabide whenused as an add-on therapy may be not reduce seizure frequency. A largescale, randomized controlled trial with refractory partial epilepsy over agreater period of time is required in future clinical researches.

p401LEVETIRACETAM IN ORAL SOLUTION – SAFETY,TOLERABILITY AND EFFICACY IN PAEDIATRICPATIENTS. SINGLE-CENTRE CLINICAL TRIALO. Horak, and H. OslejskovaEpilepsy Center Brno, Brno University Hospital and Faculty ofMedicine, Masaryk University, Brno, Czech Republic

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Purpose: To determine the occurrence, severity and impact of adversereactions (ADRs) of levetiracetam in oral solution, and so assess thegrade of tolerability for this drug-form in paediatric patients. In addition,to focus on the spectrum of efficacy.

Method: A single-centre clinical trial of 19 paediatric patients (medianof age 2,67 years) treated with levetiracetam in oral solution over a 6months period was conducted (monotherapy in 68,4%). Adverse drugreactions (ADRs) have been judged in 3-degree scale in three visits sincethe initiation of the treatment. Descriptive statistics such as minimum,maximum, mean, median and percentiles were used to describe the doseprofile. 100% stacked bar graphs were used to describe proportions ofpatients according to number of seizures as well as according to ADRsseverity. The assessment of efficacy was proved by means of non-para-metric McNemar's test for the each type of epileptic seizure and each per-iod individually.

Result: 68, 4% of patients had no ADRs. In 31, 6% of cases the therapywas associated with (mostly weak) negative effect on mood, less oftenthe nausea, aggressiveness, fatique or agility occurred. Only one patienthad to stop the therapy. The relation with dose-titration profile wasn'timproved. Statistically significant efficacy in secondary generalisedtonic-clonic seizures and partial complex seizures was proved.

Conclusion: Levetiracetam in oral solution seems to be well toleratedand safe drug in paediatric patients. ADRs, mostly of weak severity, wereobserved in 31, 6%. Emotional lability was the most frequent ADRs.

p402META-ANALYSIS OF NONPSYCHOTIC BEHAVIORALTREATMENT EMERGENT ADVERSE EVENTS INBRIVARACETAM AND LEVETIRACETAM DEVELOP-MENT PROGRAMSJ. D’Souza*, M. Johnson�, and S. Borghs**UCB Pharma, Brussels, Belgium; and �UCB Pharma, Raleigh,USA

Purpose: Brivaracetam (BRV) is a novel high-affinity synaptic vesicleprotein 2A (SV2A) ligand which also displays inhibitory activity at neu-ronal voltage-dependent sodium channels. Levetiracetam (LEV) hasbeen reported to be associated with behavioral problems. The objectiveof this analysis was to compare the incidence of behavioral problems inLEV and BRV clinical trials.

Method: All global phase II/III double-blind placebo-controlled trialsof adjunctive LEV (n = 4) and BRV (n = 5) in adults with uncontrolledfocal epilepsy were analyzed. The number of subjects with at least onenonpsychotic behavioral treatment emergent adverse event (TEAE) wascalculated for LEV, BRV, and respective placebo groups. Preferred termswere selected a priori from the psychiatric System Organ Class of Med-DRA 9.0. Placebo-adjusted incidence was compared using the Mantel-Haenszel odds ratio stratified by study and 95% confidence interval.

Result: The incidence of nonpsychotic behavioral TEAEs was found tobe a third lower in BRV (83/1214, 6.8%) compared with LEV (73/672,10.9%), whereas the incidences in placebo arms were similar (18/425,4.2% and 17/351, 4.8%, respectively). The placebo-adjusted incidenceswere 2.6% for BRV and 6.1% for LEV. The odds ratio (BRV/LEV) was0.68 [95% CI 0.32–1.45]. Subjects without concomitant LEV treatedwith BRV experienced a similar rate of nonpsychotic behavioral TEAEs(67/983, 6.8%) compared with subjects taking concomitant LEV (16/231, 6.9%) (corresponding placebo groups: 7/79, 8.9% versus 11/346,3.2%).

Conclusion: Despite lacking statistical significance, the absolute andplacebo-adjusted incidence of nonpsychotic behavioral TEAEs werefound to be numerically lower for BRV compared with LEV.

p403EVALUATION OF SUDDEN UNEXPECTED DEATH INEPILEPSY (SUDEP) OCCURRING IN LAMOTRIGINE(LTG) CLINICAL TRIALST. Tomson*, L. Hirsch�, D. Friedman�, N. Bester§, A. Hammer–,M. Irizarry–, L. Ishihara§, A. Krishen–, T. Spaulding–, A. Wamil–,and R. Leadbetter–

*Karolinska Institute, Stockholm, Sweden; �Yale University,New Haven, CT, USA; �New York University Langone MedicalCenter, New York, NY, USA; §GlaxoSmithKline, Uxbridge, UK;and –GlaxoSmithKline, Research Triangle Park, NC, USA

Purpose: Previous non-randomized studies reported an increased risk ofSUDEP with LTG, but the association may be confounded by tonic-clo-nic seizure frequency, polypharmacy, and other potential SUDEP riskfactors. We evaluated the risk of SUDEP with LTG compared to otherAEDs and placebo in randomized controlled clinical trials conducted byGlaxoSmithKline.

Method: Among 7,774 subjects in 42 randomized clinical trials, therewere 39 all-cause deaths. Ten deaths occurred >2 weeks after discontinu-ation of study medication and were excluded from on-treatment events.Narrative summaries of deaths were independently reviewed by threeclinical experts (TT, LH, DF), blinded to randomization arm. The risk ofdefinite or probable SUDEP (Annegers’ criteria,1997) was comparedbetween treatment arms for each trial design (placebo-controlled, active-comparator, cross-over), using exact statistical methods.

Result: Of 29 on-treatment deaths, there were 8 definite/probable SU-DEPs, 4 possible SUDEPs and 17 non-SUDEPs. The overall rate of defi-nite/probable SUDEP for LTG was 2.2 per 1000-patient-years (95%CI=0.71–5.4). The odds ratios (OR) for on-treatment, definite/probableSUDEP in LTG arms relative to comparator arms, adjusted for length ofexposure and trial, were—placebo-controlled: OR=0.22 (95%CI 0.00–3.14; p = 0.26); active-comparator: OR=2.18 (95%CI 0.17–117; p = 0.89);placebo-controlled cross-over: OR=1.08 (95%CI 0.00–42.2; p = 1.0).

Conclusion: Although the rate of SUDEP was not statistically differentbetween LTG and comparator groups, the confidence intervals were wideand a clinically important increased or decreased risk cannot be excluded.

Funded by GlaxoSmithKline.


p404IMPROVING THE DEVELOPMENT OF PROMISINGDRUG CANDIDATES: PRECLINICAL SOLUTIONS IN ACHRONIC MOUSE MODEL OF MESIAL TEMPORALLOBE EPILEPSYM. Langlois, C. Bouyssieres, V. Duveau, C. Dumont, andC. RoucardSynapCell, La Tronche, France

Purpose: Despite the development of new compounds, more than 30%of patients with epilepsy are still resistant to antiepileptic drugs (AEDs).Pharmaceutical industry clearly needs new preclinical strategies toimprove AED discovery and development. Accordingly, chronic animalmodels of epilepsy that are resistant to one or several AEDs appear ofgreat interest.

Method: Mesiotemporal lobe epilepsy (MTLE) is the most commonform of epilepsy that is refractory to AEDs. During the past ten years, amodel of MTLE in adult mice has emerged where spontaneous recurrentfocal seizures with mild behavioral expression are observed. A unilateral

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injection of kainate (KA) into the dorsal hippocampus induces an ipsilat-eral hippocampal sclerosis along with the occurrence of spontaneousrecurrent hippocampal paroxysmal discharges (HPD). These HPDdevelop during the first 3 weeks post KA and then remain stable and ste-reotyped for the whole life of the animals and occur spontaneously about45 times per hour.

Result: By using this MTLE mouse model, SynapCell has developed abroad range of preclinical solutions to better identify promising drug can-didates. First, the in vivo screening protocol allows testing of smalllibraries of compounds and relies on quantitative EEG evaluation of theefficacy of new AEDs on highly recurrent HPDs. Then, promising drugcandidates can be further studied for their dose response or long lastingeffects with acute or chronic treatments.

Conclusion: Altogether, this chronic model of MTLE reproducesbehavioral, electroclinical and histopathological features of humanMTLE and represents a unique tool to identify new AEDs potentiallyefficient in drug-resistant MTLE patients.

p405ESLICARBAZEPINE DOES NOT ALTER PROLIFERA-TION AND CELL CYCLE DISTRIBUTION OF NEURALSTEM CELLS ISOLATED FROM THE RAT SUBVEN-TRICULAR ZONEM. I. Morte*, B. P. Carreira*, P. Soares-Da-Silva�,I. M. Araffljo�, and C. M. Carvalho**University of Coimbra, Coimbra, Portugal; �University ofPorto, Porto, Portugal; and �University of Algarve, Faro,Portugal

Purpose: The effect on the proliferation of cultured neural stem cellsisolated from the rat subventricular zone by eslicarbazepine acetate(ESL) and its metabolites, eslicarbazepine, and R-licarbazepine (R-Lic),carbamazepine (CBZ), oxcarbazepine (OXC), lamotrigine (LTG) andvalproic acid (VPA) was investigated.

Method: Cell proliferation was determined by the incorporation of 5-ethynyl-2¢-deoxyuridine (EdU) after exposure of the cells to AEDs for 24h, analysed by flow cytometry, together with cell cycle analysis per-formed by quantitative fluorescence.

Result: The number of EdU-positive cells, with a median of 11.52 cells(10.47–12.62 cells) in basal conditions, was decreased by all the AEDsexcept eslicarbazepine (10–300 lM). Number of cells was decreased by60% after treatment with ESL (30 lM), by 40% after treatment with R-Lic (1 lM), between 65–75% after treatment with CBZ (10–300 lM), by60% or 90% after treatment with OXC (30–300 lM), by 30% after treat-ment with LTG (300 lM), and by 98% after treatment with VPA (1–3mM). Cells in G0/G1 phase increased by 2% after treatment with LTG(10 lM) and by 13% after treatment with VPA (1 mM). The number ofcells in S phase was unchanged by the AEDs [median of 3.4% (2.6–4.0%)]. However, the number of cells in G2/M phase was increased by90% after exposure to OXC (300 lM), while VPA (1–3 mM) decreasedthe number of G2/M cells by 65–70%.

Conclusion: Eslicarbazepine does not alter the proliferation of neuralstem cells, whereas CBZ, OXC and VPA impaired proliferation of neuralstem cells.

p406STEADY-STATE PHARMACOKINETICS AND TOLER-ABILITY OF ONCE-DAILY AND TWICE-DAILY REGI-MENS OF ESLICARBAZEPINE ACETATE IN HEALTHYVOLUNTEERSM. Vaz-Da-Silva*, A. Falc¼o�, T. Nunes�, L. Almeida§, andP. Soares-Da-Silva*

*University of Porto, Porto, Portugal; �4Health Consulting,Cantanhede, Portugal; �BIAL – Portela & Ca. SA, S¼o Mamededo Coronado, Portugal; and §University of Aveiro, Aveiro,

Purpose: In a phase II placebo-controlled, adjunctive therapy study inadult patients with partial-onset seizures eslicarbazepine acetate (ESL)800 and 1200 mg/day once-daily (QD) was found to be efficacious andwell tolerated. However, the same dose given twice-daily (BID) was notsignificantly more efficacious than placebo (Epilepsia, 48, 497–504,2007). The present study investigated the steady-state pharmacokineticsof QD and BID regimens of ESL in healthy volunteers. Tolerability wasalso assessed.

Method: Single centre, open-label, randomised, three-way crossoverstudy in 12 healthy volunteers. The study consisted of two 8-day treat-ment periods separated by a washout period of 10–15 days. In each treat-ment period the volunteers received a daily dose of either ESL (900 mgQD or 450 mg BID) or 450 mg of OXC BID (data not shown).

Result: Eslicarbazepine was the major drug entity in plasma, accountingfor 94.6% and 94.0% of total exposure with ESL QD and ESL BID,respectively. Eslicarbazepine (Cmax) was 34% higher with ESL QD incomparison with ESL BID; AUC0–24 was 1133.71 and 1101.16 mmol*h/L, respectively. Trough plasma eslicarbazepine before the last dose was24.2% lower in the ESL QD in relation to ESL BID (27.45 and 36.21lmol/L, respectively). A total of 18 treatment-emergent adverse eventswere reported in each group.

Conclusion: In comparison to ESL BID, administration of ESL QDresulted in 34% higher maximum concentration of eslicarbazepine withsimilar overall exposure, which may correlate with the efficacy profilereported with ESL.

p407RETIGABINE IN CHILDREN AND ADOLESCENTSWITH PHARMACORESISTANT EPILEPSIES – DOCU-MENTATION WITH THE ELECTRONIC TREATMENTDIARY EPI-VISTA�K. Groening*, C. Dreiwes�, U. Stephani�, and R. Boor�

*Klinik f�r Neuropdiatrie, Kiel, Germany; and �NorddeutschesEpilepsiezentraum, Schwentinental, Germany

Purpose: The anticonvulsant retigabine exhibits a novel mechanism ofaction opening neuronal KCNQ/Kv7 potassium channels. Investigationson effects and side-effects in children/adolescents are not available. Weanalysed results of individual treatment trials with retigabine in pharma-coresistant epilepsies, focussing on seizure frequency and tolerability.

Method: 17 patients (1;10–19 years) with pharmacoresistant epilepsieswere treated with retigabine. 12 patients documented seizures, dose andside effects in EPI-Vista. We compared the number of seizures during thelast 4 weeks before starting treatment (baseline) with 4 weeks after reach-ing 10 mg/kg body weight/day or after the patient became seizure free orhad side-effects earlier during titration.

Result: The patients were treated with 4–13 (median 6.5) anticonvul-sants before starting retigabine, duration of epilepsy was 1;2–11;6 (med-ian 8) years. The number of seizures at baseline were 8 -1045 (median47), in the observation period 0 – 1216 (median 15). Three patientsshowed reduction of seizure frequency of more than 50%. The dose whenside effects were present was 6.3 – 16.37 (median 10,2) mg/kg bodyweight. 2 patients did not have side effects. The side effects were fatigue(6·), speech disorders (3·), concentration disturbances (3·), sleep disor-der, hallucination, agitation, increase of seizures, personality changes,elevated lever values. All side effects vanished when reducing/endingtreatment with retigabine.

Conclusion: Retigabine is a novel anticonvulsant which showed reduc-tion of seizures in 3/12 children with pharmacoresistant epilepsies. Side

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effects appeared in most cases but were reversible when withdrawing re-tigabine. Further studies are needed to define the group of children whereretigabine is most powerful.

p408THE EFFECTS OF ESLICARBAZEPINE, R-LICA-RBAZEPINE, OXCARBAZEPINE, AND CARBAMAZE-PINE ON SODIUM CURRENTS THROUGH NAV1.2CHANNELSN. Pires*, K. Brady�, S. Hebeisen�, and P. Soares-Da-Silva�

*BIAL – Portela & Ca. SA, S¼o Mamede do Coronado,Portugal; �B’SYS GmbH, Witterswil; and �University of Porto,Porto, Portugal

Purpose: Eslicarbazepine acetate (ESL) is a once-daily antiepilepticdrug approved in Europe as adjunctive therapy for refractory partial-onset seizures in adults. ESL undergoes rapid and extensive first passmetabolism via hydrolysis to eslicarbazepine, its major active metabolite.This study was aimed to determine the effects of eslicarbazepine, R-lica-rbazepine (minor metabolite of ESL), oxcarbazepine (OXC), and carba-mazepine (CBZ) on the rat NaV1.2 sodium channel expressed in CHOcells.

Method: About 24–48 hours following transfection with rat NaV1.2cDNA, cells were ready for electrophysiological experiments. Thewhole-cell patch-clamp technique was used to investigate the effects ofeslicarbazepine, R-licarbazepine, OXC, and CBZ on NaV1.2 inward peakcurrents. These compounds were tested at various holding potentials()80 mV and )70 mV).

Result: With the exception of CBZ, the potency of inhibition was highlysensitive to the holding potential, increasing with depolarisation, but theaffinity of eslicarbazepine was approximately 2- to 3-fold lower than thatof OXC and CBZ in more depolarized conditions. CBZ was endowedwith the potency to inhibit inward NaV1.2 sodium currents at )80 mVand )70 mV holding potentials.

Conclusion: Eslicarbazepine demonstrated a greater selectivity for theinactive state of NaV1.2 sodium channels, which is the common featureof the rapidly firing neurons, over their resting state as compared to CBZand OXC.

p409EFFICACY OF LACOSAMIDE IN DRUG-RESISTANTFOCAL EPILEPSYP. Bellas-Lamas, A. Fraga-Bau, B. Rodriguez-Acevedo,E. Alvarez-Rodriguez, and J. Gomez-AlonsoUniversity Hospital Xeral-Cies, Vigo, Spain

Purpose: New antiepileptic drugs (AEDs) may offer some hope inrefractory epilepsy, even in cases of ‘‘absolute drug-resistance’’, or‘‘grade III drug-resistance’’, that had failed >6 AED trials. We analyzedour experience with lacosamide in refractory focal epilepsy.

Method: We prospectively registered all patients treated with lacosa-mide, as adjunctive therapy, until December 2010, at the Epilepsy Clinicof a general hospital in NW Spain. In February 2012, we evaluated theoutcomes of those trials following the standards of the International Lea-gue Against Epilepsy. The daily dose of lacosamide usually prescribedwas 50 mg for two weeks, 100 mg for another two weeks, and then 200mg or more.

Result: Although lacosamide was administered to 88 patients with focalepilepsy, 12 trials were excluded because their results were undetermined

(for early adverse effects in 8, non-compliance 3, and concomitantpseudoseizures 1). Among the 76 patients with informative trials, 15(19.73%) became seizure-free for more than 12 months (mean: 17.67months [SD: 3.67], range: 12–24). The mean dose of lacosamide used inseizure-free patients was 246.66 mg. The mean number of previouslyfailed AED trials, in the group of 76 patients, was 8 (SD: 3.51, range: 2–16). When the analysis was restricted to the 56 patients who had failed >6AED trials, the number of seizure-free patients was 7 (12.5%).

Conclusion: In our study, lacosamide showed a promising result whenused as adjunctive therapy in patients with previously drug-resistant focalepilepsy, included those who had previously failed six or more AEDtrials.

p410PRESCRIBING PATTERN OF OLDER VERSUS NEWERANTIEPILEPTIC DRUGS IN PATIENTS WITH EPI-LEPSY ATTENDING OUTPATIENT DEPARTMENT ATA TERTIARY CARE CENTRE IN INDIAR. Joshi, M. Tripathi, K. H. Reeta, and Y. K. GuptaAll India Institute of Medical Sciences, New Delhi, India

Purpose: The purpose of the study was to evaluate the prescription pat-tern of older and newer antiepileptic drugs (AEDs) in a representativepopulation of patients with epilepsy in the tertiary care centre in India.

Method: Prescription data of epilepsy patients attending outpatientdepartment (OPD) of neurology, AIIMS, India was obtained. Demo-graphic variables including age, sex, diagnosis, age at onset of seizures,frequency of seizures and use of all AEDs were noted. Descriptive analy-sis of the use of older and newer AEDs was done and their different com-binations were studied.

Result: The prescriptions of 1000 epileptic patients attending OPD from1st October 2010 to 27th January 2012 were evaluated. The demographyshowed 63.8% males, 36.2% females; mean age 23.2 years (range: 4months to 77 years). The cases of generalized and focal seizures were50.9% and 49.1% respectively. A total of 14 AEDs were prescribed. Thefour most frequently prescribed AEDs were sodium valproate (46.6%),clobazam (40.4%), carbamazepine (31.2%), levetiracetam (30.1%). The32.7% of the patients received monotherapy. The common AEDs used onmonotherapy were sodium valproate (33.6%), carbamazepine (25.1%),phenytoin (23.5%). Of the 67.3% patients received polytherapy, the threemost common AED combinations were phenytoin + clobazam (46),sodium valproate + clobazam (40), phenytoin/carbamazepine + sodiumvalproate + clobazam (27). The recent AED introduced in 2010 in Indiawas lacosamide used in 25 patients as add on therapy.

Conclusion: An increasing trend of use of newer AEDs needs carefulscrutiny in terms of cost, efficacy and safety.

p411RUFINAMIDE'S EFFICACY AND SAFETY IN CHILD-HOOD EPILEPSY SECONDARY TO BRAIN MALFOR-MATIONSR. Moavero*, F. Madeddu�, D. Pruna�, M. Balestri�, L. Fusco�,N. Specchio�, A. Capuano�, D. J. Claps�, P. Curatolo*,F. Vigevano�, and R. Cusmai�

*Tor Vergata University Hospital of Rome, Rome, Italy;�Azienda Ospedaliero Universitaria of Cagliari, Cagliari, Italy;and �Bambino Ges�’’ Children's Hospital of Rome, Rome, Italy

Purpose: Aim of this study was the evaluation of efficacy and tolerabil-ity of add-on Rufinamide in pediatric patients with focal symptomaticepilepsy due to brain malformations.

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Method: We retrospectively reviewed the clinical and electroencepha-lographic data of 32 children with refractory seizures symptomatic of dif-ferent brain malformations treated with Rufinamide. Rufinamide wasslowly titrated up to 40 mg/Kg/day (range 10–40 mg/Kg/day, mean 33mg/Kg/day). All the patients have been followed-up for at least 12months. Patients have been considered responders if seizure reductionwas greater than 50%.

Result: 46,9% of patients presented focal cortical dysplasia, 21,9%pachygyria, 12,5% lissencephaly, 6,2% polymicrogyria, 3,1% ulegyria,3,1% tuberous sclerosis, 3,1% schizencephaly, and 3,1% Walker-War-burg syndrome. 81,2% of patients presented focal motor and complexpartial seizures, 15,6% focal motor seizures and the last patient only com-plex partial seizures. At the final follow-up 50% of patients wereresponders; seizure reduction was greater than 90% in 9% of cases,between 75% and 90% in 19%, and ranging from 50 to 75% in 22%. Allthe non-responder patients (50%) discontinued Rufinamide. 31,2% ofsubjects presented mild and transient side effects; only in one case(3,1%) dosage reduction was necessary to control irritability. In anotherpatient (3,1%) Rufinamide was discontinued because of persisting anor-exia.

Conclusion: Our results suggest that Rufinamide can be considered as avaluable adjunctive therapeutic option for children presenting refractoryseizures symptomatic of brain malformations.

p412ON THE USE OF INTRA RECTAL VALIUM INPATIENTS WITH DRAVET SYNDROME: FAMILIES’EXPERIENCER. Nabbout*, N. Chemaly�, and N. Coque�

*Hopital Necker-Enfants Malades, Paris, France; �Paris,France; and �Brest, France

Purpose: Intra rectal Diazepam (DZ) remains the first rescue medica-tion for acute prolonged convulsive seizures in children. In this study, weaimed at assessing the experience of the families of patients presentingDravet syndrome (DS) concerning DZ use.

Method: We invited 53 families of patients with DS to complete anauto-administered on-line questionnaire. Questions addressed the differ-ent aspects of intra rectal DZ use: usual administrators, and time, easi-ness, and risk of errors in the preparation and administration. Parentswere questioned about their feeling concerning efficacy, usefulness inemergency setting, facility of its administration, and possible refuse ofcare givers to use it.

Result: 52 families answered the questionnaire. DZ was usually admin-istered by mothers and less frequently by other care givers. Almost allparents (92%) agreed on its efficacy. However, 50% found that prepara-tion and administration are affected by errors especially when carried outof the parents’ presence. Many educational and non-medical institutionsrefused to use DZ.

Conclusion: Parents confirm the efficacy of intra rectal DZ and empha-sized the need for a medication that is easier to prepare and administer.

p413COMPARATIVE BIOAVAILABILITY STUDY OF TWODIFFERENT SOURCES OF ESLICARBAZEPINE ACE-TATE IN HEALTHY SUBJECTSR. P. Sousa*, R. Lima*, T. Nunes*, and P. Soares-Da-Silva�

*BIAL – Portela & Ca. SA, S¼o Mamede do Coronado,Portugal; and �University of Porto, Porto, Portugal

Purpose: To demonstrate the bioequivalence (BE) between two activeproduct ingredient (API) sources of eslicarbazepine acetate (ESL) [cur-rent API source – marketed formulation (MF) versus new API source –to-be-marketed (TBM)].

Method: Two-centre, open-label, randomized, gender-balanced, single-dose, laboratory-blinded, two-period, two-sequence, crossover study intwo groups of 20 healthy subjects. Subjects randomly received on period1 and 2 either a single tablet of ESL (MF) or a single tablet of ESL(TBM), separated by a wash-out of at least seven days between doses.Two dosage strengths were studied – 400 mg in one group and 800 mg inthe other. For all subjects, blood samples (4 mL) were drawn for the assayof plasma ESL and its active metabolite eslicarbazepine at pre-dose andthen 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose on eachdosing period.

Result: At the two studied dosage levels, 400 mg and 800 mg, the90% back-transformed confidence intervals for Cmax, AUC0-t andAUC0-¥ ratios of the Test formulation (TBM) and Reference (MF)formulation were all contained in the bioequivalence range of 0.8–1.25. Additionally, at both dose levels, no evidence of differencebetween Test and Reference products in tmax (p > 0.05) was found.Study treatments, whatever the dosage and formulation, were well tol-erated.

Conclusion: The oral formulations containing 400 mg or 800 mg ofESL of the TBM source are bioequivalent to the MF source for both 400mg and 800 mg of ESL.

p414MODELLING THE COGNITIVE EFFECTS OF COM-MON ANTIEPILEPTIC DRUGS: A CROSS SECTIONALHEAD-TO-HEAD COMPARISON USING THE EPI-TRACKC. Helmstaedter, and J. WittBonn, Germany

Purpose: Although the cognitive side effects of AEDs are more orless known, the risk profiles of the respective drugs must be extrapo-lated from a plethora of studies with heterogeneous study designs,control conditions and assessments. In this regard, we aimed at across-sectional head-to-head comparison of the cognitive effects ofcommon AEDs given in mono- or polytherapy and using the samescreening test.

Method: Using a cross-sectional controlled study design, 542 untreatedepilepsy patients, 1074 patients on mono-, and 1357 patients on polyther-apies were evaluated in regard to a set of executive functions. For thispurpose, we applied a 12-minute tool (EpiTrack�) which, in its secondedition, had newly been standardized for an age range of 16–87 years. in689 healthy subjects.

Result: In the off drug condition, 42% of the patients were impaired.Compared to this, the odds ratios increased from 1.4 with monotherapy to7.8 with 4 drugs in polytherapy. Linear regression indicated worse Epi-Track performance with a higher number of AEDs, TPM, ZNS, or GBPand better performance with LEV or LTG. Education appeared to be aprotective factor, female gender an additional risk factor. The regressionmodel, however, only explains 23% of the observed variance. Followingodds ratios, AEDs could be grouped into three classes with ratios of 1.9–2.6 (LTG, LEV, CBZ, OXC), 2.6–3.6 (VPA, PB, PGB, LCM, GBP,PHT) and 4.1–5.3 (ZNS, TPM, CLB).

Conclusion: This is the first study, which, using a single assessmenttool, models and replicates the known cognitive effects of common AEDsin a cross-sectional study design.

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Abstracts



p415DESIGN OF A PHASE III, DOUBLE-DUMMY, ACTIVE-CONTROLLED, MULTI-NATIONAL NON-INFERIOR-ITY MONOTHERAPY TRIAL OF ESLICARBAZEPINEACETATE VERSUS CONTROLLED-RELEASE CARBA-MAZEPINE IN ADULTS WITH PARTIAL-ONSET SEI-ZURESJ. Moreira*, E. Trinka�, F. Mota*, T. Nunes*, and P. Soares-Da-Silva�

*BIAL – Portela & Ca. SA, S¼o Mamede do Coronado,Portugal; �Paracelsus Medical University, Salzburg, Austria;and �University of Porto, Porto, Portugal

Purpose: Eslicarbazepine acetate (ESL) was approved by the EuropeanMedicines Agency in 2009 as adjunctive therapy in adults with partial-onset seizures, with or without secondary generalization. This phase-III,randomised, double-blind, active-controlled, non-inferiority study aimsto demonstrate the efficacy and safety of once-daily ESL as monotherapytreatment for newly diagnosed adults with POS in comparison to twice-daily controlled-release carbamazepine (CBZ-CR).

Method: Patients (>18 year) with >2 unprovoked seizures in the pastyear and >1 in the last 3-months will be randomised in a 1:1 ratio toreceive ESL 800 mg once-daily or CBZ-CR 200 mg twice-daily during a26-week evaluation-period. In case of seizure occurrence during the eval-uation-period, subjects are titrated to dose-levels B (1200 mg once-daily/400 mg twice-daily) and C (1600 mg once-daily/600 mg twice-daily). Toassess maintenance of effect over 1-year, a 26-week maintenance-periodwill follow. Exit criteria include seizures at dose-level C at evaluation-period or at any dose-level in the maintenance-period. The primary end-point is seizure-freedom in the 26-week evaluation-period at the lastreceived dose level. The sample size was calculated to achieve a > 90%power to establish non-inferiority, using a )12% margin. Secondary end-points include tolerability, QOLIE)31, sedation, and clinical laboratoryassessments.

Result: The study is expected to be completed by the end of 2013.

Conclusion: The use of a non-inferiority design implies the pre-defini-tion of a clinically relevant margin and adequate power to detect non-inferiority versus a gold standard. To our knowledge this is the first piv-otal study to fully achieve those requirements.

p416ZONISAMIDE AS ADD-ON TREATMENT DOES NOTAFFECT NOCTURNAL SLEEP AND VIGILANCE INPATIENTS AFFECTED BY FOCAL EPILEPSY: A POLY-SOMNOGRAPHIC STUDYA. Romigi, F. Izzi, F. Placidi, S. Zannino, E. Evangelista, C. DelBianco, F. Cum, and M. G. MarcianiUniversity of Rome Tor Vergata, Rome, Italy

Purpose: Epilepsy are particularly sensitive to the sleep disruptioninduced by antiepileptic drugs (AEDs). AEDs have the potential to eitherimprove or worsen sleep and sleep disorders in epileptic patients. Zonisa-mide (ZNS) is a new AED approved in USA and Europe as adjunctivetherapy for focal epilepsy. To date the effects of ZNS on sleep and vigi-lance in focal epilepsy are not yet studied. The purpose of our study is toevaluate the effects of ZNS adjunctive therapy on nocturnal sleep bymeans of ambulatory polysomnography (A-PSG) and Pittsburgh SleepQuality Index (PSQI) and on daytime somnolence by means of multiplesleep latency test (MSLT) and Epworth Sleepiness Scale (ESS) in focalepilepsy as standard methodology.

Method: Twelve patients affected by focal epilepsy underwent A-PSG,MSLT, and a subjective evaluation of nocturnal sleep by means of PSQIand daytime somnolence by means of the Epworth Sleepiness Scale(ESS), before and after 3 month treatment with ZNS. Recordings wereevaluated in according to standard criteria. The study was single-blind.PSG data, MSLT, both PSQI and ESS scores were calculated before andafter ZNS treatment. Statistical analysis was performed by means of thenon-parametric Wilcoxon test. Bonferroni correction was applied whenrequired.

Result: ZNS induced a decrease of seizures >50% in 9 out of 12 patients(75%). ZNS did not induce any significant differences of nocturnal PSGparameters and mean sleep latency as measured by means of MSLT. Nosignificant changes were detected in both PSQI e ESS scores after ZNSaddition.

Conclusion: To our knowledge this is first study focusing about theeffects of ZNS on nocturnal sleep and diurnal sleepiness. Firstly ZNS ad-juntive treatment seems to be effective in focal epilepsy in our narrowsample as reported in several clinical trials3. In addition ZNS does notinduce negative effects on sleep-wake cycle and diurnal sleepiness asevaluated by means of a comprehensive objective e subjective evalution.

p417EFFICACY OF PERAMPANEL, A SELECTIVE AMPAANTAGONIST, IN COMPLEX PARTIAL AND SECOND-ARILY GENERALIZED SEIZURES: A POOLED ANALY-SIS OF PHASE III STUDIES IN PATIENTS WITHTREATMENT-RESISTANT PARTIAL-ONSET SEI-ZURESB. J. Steinhoff*, H. Gauffin�, P. Mckee�, D. Squillacote§,H. Yang§, D. Kumar§, and A. Laurenza§

*Epilepsiezentrum Kork, Kehl-Kork, Germany; �LinkçpingUniversity, Linkçping, Sweden; �The James Cook UniversityHospital, Middlesbrough, UK; and §Eisai Neuroscience ProductCreation Unit, Woodcliff Lake, NJ, USA

Purpose: In this sensitivity/subgroup analysis we summarize the effi-cacy of perampanel in both complex partial plus secondarily generalizedseizures (CPS+SGS) and secondarily generalized seizures (SGS) acrossphase III studies according to actual doses of perampanel achieved. Therandomized population, with prespecified endpoints, will be presented inthe poster.

Method: Following Baseline, patients were randomized to once-dailyplacebo, perampanel 2, 4, 8, or 12 mg. Endpoints included percentchange in CPS+SGS and SGS frequency/28 days (vs Baseline), andCPS+SGS and SGS 50% responder rates. Analyses were based on lastactual perampanel doses in patients completing 19 weeks’ treatment(excluding Central/South American patients due to significant treatment-by-region interactions).

Result: Overall, 442, 180, 172, 431, and 254 patients were randomizedto placebo, perampanel 2, 4, 8, 12 mg, respectively; 1264 patients com-pleted the studies. The numbers of patients achieving each actual dosewere: 348, 161, 159, 46, 287, 14, 114 for placebo, perampanel 2, 4, 6, 8,10, 12 mg. Median percent changes in CPS+SGS frequency were)14.6% (n = 319), )26.6% (n = 150), )35.6% (n = 145), )35.9% (n =267), )30.3% (n = 104) for placebo, perampanel 2, 4, 8, 12 mg actualdoses. Responder rates were 21.9%, 29.3%, 37.9%, 40.1%, 39.4%. Med-ian percent changes in SGS frequency were )19.5% (n = 133), )27.9%(n = 60), -54.6% (n = 66), )60.8% (n = 112), )56.0% (n = 43) for pla-cebo, 2, 4, 8, 12 mg. Responder rates were 38.3%, 43.3%, 53.0%, 56.3%,53.5%.

Conclusion: In this sensitivity/subgroup analysis of phase III trials, per-ampanel decreased CPS+SGS and SGS frequency and increased respon-der rates, compared with placebo. Support: Eisai Inc.

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Abstracts


p418LONG-TERM COGNITIVE EFFECTS OF TREATMENTWITH MONOTHERAPY CARBAMAZEPINE (CBZ) ANDVALPROATE (VPA)D. Ijff, M. Majoie, and A. AldenkampKempenhaeghe, Heeze, The Netherlands

Purpose: So far the information on cognitive effects of antiepileptictreatment is based on short-term trials. The long-term effects have, as yet,not been studied. Mostly fluid cognitive functions are assessed as nochanges are expected in higher-order function in such a short period. It isunknown whether higher functions are at risk with longer treatment inter-vals. In this open clinical cohort study the long-term cognitive effects ofmonotherapy carbamazepine and valproate were evaluated in childrenand adults with epilepsy.

Method: Patients were only included when they had been on monother-apy CBZ or VPA from epilepsy onset without any switch to other medi-cation. Outcome measures included WISC-III/WAIS-III1,2 and cognitivetests (FePsy)3.

Result: Thirty-five children (average treatment length 3.8 years) and 22adults (average treatment length 7.8 years) were included with CBZ.Forty-six children and 17 adult patients were included with VPA. Aver-age length of treatment in both VPA-groups was 3.5 years. Signs for mildmental/psychomotor slowing without any differences between CBZ andVPA were found. Children on CBZ had lower intelligence scores than onVPA. However, this result was not found for adults. The two treatmentgroups did not differ in type of epilepsy. There is a high inverse correla-tion between length of treatment and IQ-scores only for children on CBZ.

Conclusion: Our study shows evidence that at long-term CBZ mayimpact higher-order cognitive function and even intelligence in chil-dren. As this effect was not found for adults, this suggests that long-term treatment with CBZ may influence the maturation of the brain inchildren.

p419IMPLANTATION OF PHENYTOIN-LOADED POLYCAP-ROLACTONE MICROSPHERES IN A RAT MODEL OFTEMPORAL LOBE EPILEPSYJ. Sui*, A. Halliday�, K. Mclean*, T. Wilson�, S. Moulton§,G. Wallace§, R. Balson–, A. Lai*, N. Beattie*, and M. Cook**St Vincent's Hospital, Melbourne, Vic, Australia; �University ofMelbourne, St. Vincent's Hospital, Melbourne, Vic, Australia;�St Vincent's Pathology, Melbourne, Vic, Australia; §Universityof Wollongong, Wollongong, NSW, Australia; and –BionicsInstitute, Melbourne, Vic, Australia

Purpose: The main purpose of this study is to explore the potential ther-apeutic effects of intracerebral polymer-based anticonvulsant delivery intreating generalized and partial seizures.

Method: Phenytoin (PHT)-loaded polycaprolactone (PCL) micro-spheres were produced by performing an emulsion process. The actualdrug loading and releasing profile was determined using high perfor-mance liquid chromatography. Temporal lobe epilepsy model was estab-lished by unilateral injections of tetanus toxin into right hippocampus ofadult male Sprague-Dawley rats. PHT PCL spheres were ipsilaterallyinjected in the adjacent region. Seizure phenotypes and cortico-electricaldischarges were detected and recorded by a twenty-four hours video elec-troencephalography system equipped with ProFusion�. Animals werekilled eight weeks after toxin injection, and biocompatibility wasassessed by immunohistochemistry.

Result: The PCL microspheres were 30–50 lm in diameter. In vitrostudy revealed PCL microspheres released a substantial amount of PHT

in the first twenty-four hours following incubation regardless of drugloading percentage, and then demonstrated a steady release until eightweeks. We confirmed the neuronal loss in CA1 in the lesioned hippocam-pus of tetanus-treated rats. Spontaneous seizures which resemble humangeneralized tonic clonic seizures, absence and myoclonic seizures havebeen observed. The PHT-loaded microsphere implanted rats exhibited areduced number of convulsive seizures as illustrated by attenuated sei-zure scores.

Conclusion: This study demonstrates the efficacy of PHT-loaded PCLmicrospheres in attenuating generalized seizures in a rat model of tempo-ral lobe epilepsy. This may warrant further studies for focal delivery ofpolymer-based anticonvulsants in treating partial and secondary general-ized seizures.

p420SEIZURE FREEDOM ON ANTIEPILEPTIC MONO-THERAPYL. J. Stephen, K. Kelly, O. Mcgowan, V. Politi, and M. BrodieWestern Infirmary, Glasgow, UK

Purpose: The goal of antiepileptic drug (AED) treatment is sustainedseizure freedom on monotherapy with no or acceptable side effects. Thisproject examined characteristics of patients seizure-free on 1 AED for ‡1year.

Method: Data were acquired by Epilepsy Unit database and case sheetinterrogation of 6821 patients registered between 1982 and 2011.

Result: Seizure freedom was achieved on 17 different monotherapies in1425 (20.9%) patients (687 men, 738 women, aged 18–94 years [median46 years]). Of these, 1131 (79.3%) had partial + secondary generalisedtonic-clonic seizures [GTCS], 294 (20.7%) had idiopathic generalisedepilepsies. First monotherapy produced complete seizure freedom in 866(60.7%) patients; the remainder controlling on 2nd (n=309, 21.7%), 3rd(n=217, 15.2%), 4th (n= 31, 2.2%), or 5th (n=2, 0.2%) schedules. Thecommonest AEDs used were sodium valproate (n=443, 31.1%), carba-mazepine (n=382, 26.8%), lamotrigine (n=318, 22.3%) and levetiracetam(n=82, 5.8%). Of patients receiving sodium valproate, 67% (n=298) took£1000mg/day (median 1000, range 400–3000), 66% of carbamazepine-treated patients received £600mg/day (median 600, range 200–2000),75% of lamotrigine-treated patients received £200mg/day (median 200,range 25–700), and 74% of levetiracetam-treated patients received£1000mg/day (median 1000, range 500–3000). There was no relationshipbetween AED dosing and schedule. Side effects (108 [81%] neurotoxic-ity, 26 [19%] other) were reported by 134 (9.4%) patients, particularlythose taking carbamazepine (60 of 382, 16%; others 73 of 1043, 7%;p<0.001).

Conclusion: Although the majority of patients became seizure-free ontheir first monotherapy, a substantial minority controlled on later sched-ules. Doses were often modest. Side effects were twice as likely with car-bamazepine.

p421ESLICARBAZEPINE ACETATE AND PLASMA LEVELSOF COMBINED ANTIEPILEPTIC DRUGS: A POPULA-TION PHARMACOKINETICS EVALUATION BASEDON DOUBLE-BLIND PHASE III CLINICAL STUDIESM. Bialer*, A. Falc¼o�, R. Costa�, N. Lopes�, T. Nunes�, andP. Soares-Da-Silva§

*The Hebrew University of Jerusalem, Jerusalem, Israel;�4Health Consulting, Cantanhede, Portugal; �BIAL - Portela &Ca. SA, S¼o Mamede do Coronado, Portugal; and §University ofPorto, Porto, Portugal

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Abstracts


Purpose: Eslicarbazepine acetate (ESL) is a once-daily voltage-gatedsodium channel blocker approved in Europe for use in adults as adjunc-tive therapy for refractory partial-onset seizures (POS) with or withoutsecondary generalisation. The variability of the population pharmacoki-netics (PK) and systemic plasma exposure to concomitant antiepilepticdrugs (AEDs) in treating patients with refractory POS were analysed todetermine the potential influence of ESL on the metabolism and PK ofconcomitant AEDs.

Method: Plasma concentrations of eslicarbazepine (main active metab-olite of ESL) and other concomitant AEDs were obtained from 641patients receiving ESL. Data were analysed using nonlinear mixed-effectmodelling (NONMEM) methods. Plasma exposure PK parameters werecalculated from individual parameters estimates derived from the model.A population PK model of trough (Cmin,ss) eslicarbazepine plasma con-centrations at steady-state was fitted.

Result: No clinically relevant changes in the mean end/initial Cmin,ss

ratios of concomitant AEDs were calculated for placebo, ESL 400 mgand 800 mg dose groups. In ESL 1200 mg treated patients, mean end/initial Cmin,ss ratios of carbamazepine (CBZ), lamotrigine (LTG), andtopiramate (TPM) were reduced by 13%, 25% and 16%, respectively.ESL slightly increased the oral clearance (CL/F) of CBZ, LTG, andTPM up to 14%, 12%, and 16%, respectively, but did not affect thatof clobazam, gabapentin, phenytoin, phenobarbital, levetiracetam andvalproate.

Conclusion: This pop-PK analysis based on integrated data from threephase III clinical studies suggests that the pharmacokinetic effect of es-licarbazepine acetate on the clearance of concomitant AEDs is unlikelyto be clinically relevant in most cases.

p422EFFECTS OF ESLICARBAZEPINE AND LACOSAMIDEON SLOW AND FAST INACTIVATION OF VOLTAGE-GATED SODIUM CHANNELSM. J. Bonif�cio*, S. Hebeisen�, and P. Soares-Da-Silva�

*BIAL - Portela & Ca. SA, S¼o Mamede do Coronado, Portugal;�B’SYS GmbH, Witterswil, Switzerland; and �University ofPorto, Porto, Portugal

Purpose: This study was aimed to determine the effects of eslicarbaze-pine, the major active metabolite of ESL, and lacosamide (LCS) on thefast and slow inactivated states of voltage-gated sodium channels(VGSC).

Method: The whole-cell patch-clamp technique was used to investigatethe effects of eslicarbazepine and LCS (both at 250 lM) on sodium chan-nels endogenously expressed in N1E-115 cells, in conditions of fast andslow inactivation of sodium currents.

Result: The shift of steady state fast inactivation curves in the hyperpo-larizing direction by LCS (-5.13 mV) was twice that by eslicarbazepine (-2.38 mV). Eslicarbazepine- and LCS-treated fast-inactivated channelsrecovered similarly to control conditions. Eslicarbazepine and LCSshifted the voltage dependence of the slow inactivation (V0.5) by -31.2mV and -53.3 mV, respectively. For eslicarbazepine and LCS, the affin-ity to the slow inactivated state was 5.9 and 10.4 times higher than to thechannels in the resting state, respectively. However, the affinity of LCS(1889 lM) for the channels in the resting state was twice that of es-licarbazepine (3302 lM). For eslicarbazepine and LCS, the time con-stants for entering the slow inactivated state were 7.00 and 4.54 s,respectively.

Conclusion: Both eslicarbazepine and LCS reduce VGSC availabilitythrough enhancement of slow inactivation, but LCS demonstrated higherinteraction with VGSC in the resting state, with fast inactivation gatingand shorter time to enter in the slow inactivated state.

p423OUTCOMES IN NEWLY DIAGNOSED EPILEPSY –WHY DO PATIENTS REMAIN UNCONTROLLED?M. Brodie*, D. Goldberg*, K. Kelly*, L. J. Stephen*, andP. Kwan�

*Western Infirmary, Glasgow, UK; and �Prince of WalesHospital, New Territories, Hong Kong

Purpose: More than 30% of a cohort of 1098 patients with newly diag-nosed epilepsy followed for 2–26 years were uncontrolled at the time ofanalysis (Brodie et al. Neurology, in press). Their clinical details wereexamined to see how many fulfilled the ILAE criteria for drug-resistantepilepsy (Kwan et al, Epilepsia 2010; 1069–1077).

Method: Casesheets from 361 patients were reviewed and data enteredinto a web-based drug response classifier programme (Hao et al. EpilepsyBehav 2011; 388–390). Those that were categorised as ‘‘undefined’’ wereinvestigated further.

Result: Thirty-two patients had died and data were incomplete for 9patients. A further nine had taken part in head-to-head placebo-controlledtrials. Of the remaining 311 patients, 136 (43.7%) fulfilled the definitionof drug-resistant epilepsy. The remaining 175 (56.3%) were classified as‘‘undefined’’. A number of reasons were identified, including trying onedrug, inadequate dosing, intermittent compliance, adverse effects at min-imal dosage, psychiatric problems affecting documentation, erratic atten-dance, social issues such as imprisonment, alcohol and recreational druguse, and patient choice (median reasons 2, range 1–4).

Conclusion: More than half of the patients with uncontrolled epilepsydid not fulfil the ILAE criteria for drug-resistant epilepsy. Further phar-macological treatment may improve their seizure control.

p424THE DIRECT COSTS OF TREATMENT WITH ANTIEPI-LEPTIC DRUGS IN BALEARIC ISLANDSM. Massot Cladera, A. Moreno Rojas, C. Barcelo Campomar,I. Barcelo Artigues, I. Chmielewska, A. B. Martinez Garcia,M. Mestre Sanso, and F. J. Molina MartinezHospital Universitario Son Espases, Palma De Mallorca, Spain

Purpose: The main objective of this study is to determine the directcosts of treatment with antiepileptic drugs (AEDs) in our community.

Method: A restrospective analysis from January 2000 to December2011, was conducted using our epilepsy consultation basedata in SonEspases Hospital to determine the direct costs of antiepileptic treatment.

Result: We analyzed 941 epileptic patients with a total of 1396 activetreatments, 579 patients receiving monotherapy treatment compared to362 patients with multiple anti-epileptic drugs (average of 2.9 AEDs).

The monthly average cost per patient was 64€ (range between 0, 99 to721). It is possible to distinguish four groups of average costs per drug:average lower than 15 € (in which we found the classic AEDs), between15 to 60 € (drugs marked in the nineties), between 60€ to 150 (such asPregabalin, Tiagabine, and Leveticetam) and more than 150€, includingthe newer drugs.

The price ranges of the average drugs were between 3€, in the case ofphenytoin, and 230€ for eslicarbacepine acetate.

It was determined that the low cost of monotherapy, 48€ per drug,compared to 235€ in the multiple antiepileptic drugs, was related to theuse of the newer and expensive antiepileptics drugs and higher doses ofmedication.

Conclusion: There is a great variability in the direct cost of different an-tiepileptic drugs. Refractory epilepsy increases the costs due to the newerand expensive antiepileptics drugs and higher doses of medication.

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Future cost-benefit studies should be used to determine the economicimpact of epilepsy treatment and whether their use is justified.

p425ASSESSMENT OF ADHERENCE TO MEDICATION INREFRACTORY PARTIAL EPILEPSYN. Carpentier, J. Jonas, C. Baumann, S. Frismand, J. Vignal,H. Vespignani, and L. MaillardCentre Hospitalier et Universitaire, Nancy, France

Purpose: The adherence to medication (AM) in refractory partial epi-lepsy (RPE) remains largely unknown. We aimed to directly assess theprevalence of AM in patients with RPE.

Method: This prospective observational study screened patients withthe diagnosis of RPE, admitted to the Nancy University Hospital betweenApril 2006 and September 2008, and referred for a 5-day pre-surgicalevaluation without any antiepileptic drug (AED) tapering. The AM wasassessed by the measurement of serum drug level. Two serum samplingsfor each treatment per patient were performed at day-1 (short-term ‘‘athome’’ adherence) and day-5 (individual reference concentration). Apatient was considered as adherent if he did not have any couple of dos-ages significantly different. A couple of dosages was significantly differ-ent if the day-1 value was inferior (infra-dosed couple) or superior(supra-dosed couple) to at least 20% of the day-5 value. Underconsumerswere non-adherent patients with one or more infra-dosed couple. Over-consumers were non-adherent patients with one or more supra-dosedcouple, without any infra-dosed couple.

Result: Forty-four of the 48 screened patients were included. Nine-teen(43.2%) of the 44 patients were adherent. The clinical characteristics ofadherent and non-adherent patients were not significantly different. Eight(32.0%) of the 25 non-adherent patients were underconsumers andseven-teen (68.0%) were overconsumers.

Conclusion: The prevalence of AM was poor (43.2%). With a low rateof underconsumers, reconsidering the diagnosis of refractory diseasedoes not appear pertinent in patients with RPE. Surprisingly, the overcon-sumers are majority. Thus AED dose-dependant adverse effects must beparticularly screened in patients with RPE.

Neuroimaging and Neurophysiology 4Tuesday, 02 October 2012

p426HUMAN HERPES 6, 7-DNAS (PCR) IN CSF OF CONVUL-SIVE CHILDRENH. R. Monavari, S. Noorbakhsh, and F. Ebrahimi TajTehran University of Medical Sciences, Iran, Tehran, Iran

Purpose: Searching the DNA-s of HHV-6 & HHV-7 in CSF samples ofconvulsive children

Method: A cross sectional study (2007–2009) done in pediatric ward inRasoul hospital, Tehran Iran. 150 CSF samples obtained from childrenwith convulsion s. Conventional and BACTEC Ped Plus medium; Latexagglutination tests; and in some cases Bacterial PCR assay used. Wesearched the DNA-s of HHV-6 & HHV-6 quantitavively by Real time -PCR in 150 CSF samples obtained from cases.

Result: Cases aged between 1–180 months, Fever (>38.5) in 74%; Irrita-bility 70%; Convulsion seen in 53% of cases. All Herpes virus detectedin 12% (18/150) cases. Both HHV-6 & HHV-7 found in 6% of all cases.

HHV-6 DNA detected in 4.7% (6) and HHV-7 DNA detected in 2cases(1.4%) with no correlation with age, sex and clinical signs.

Conclusion: HHV-6 & HHV-7 found in 6% of all studied cases.HHV-6 was slightly more frequent thanHHV-7. Our data indicate thatherpes viruses is not uncommon causes in children with meningoen-cephalitis. Our findings presumably may have differed from previousdue to epidemiologic and geographic variation (should added to differ-ences in methods, differences in age groups). Its incidence is is lowerthan other references. Further studies are needed to define the role ofHHV-6 and HHV-7 in neurologic disorders especially in immunocom-promised hosts.

p427EFFECT OF INTERICTAL EPILEPTIFORM ACTIVI-TIES AND SUBCLINICAL ELECTROENCEPHALO-GRAPHIC SEIZURE PATTERNS ON HEART RATEVARIABILITY IN TEMPORAL LOBE EPILEPSYM. Kinoshita*, Y. Demura*, S. Tomita*, R. Matsumoto�, andA. Ikeda�

*National Hospital Organization, Utano National Hospital,Kyoto, Japan; and �Graduate School of Medicine, KyotoUniversity, Kyoto, Japan

Purpose: To investigate whether interictal epileptiform activities andelectrographic seizure patterns affect heart rate variability in a patientwith temporal lobe epilepsy of bilateral independent foci.

Method: Data were obtained from a 45-year-old adult right handed malewith lateral temporal lobe epilepsy of bilateral independent foci. Long-term EEG monitoring was performed to evaluate his medically-intracta-ble daily seizures. Electroencephalography (EEG) and electrocardiogra-phy (ECG) recorded digitally with sampling rate of 500 Hz for about 60hours were analyzed. Events of a) EEG seizure pattern lasting more than3 sec, one side preceding the other by more than 1 sec, and b) unilateralinterictal EEG epileptiform activities (spikes, sharp waves, and rhythmicslow activities) during sleep, with inter-event interval of more than 62seconds, were selected. Heart rate variability indices of high frequencycomponent (HF), low frequency component (LF), and their ratio (LF/HF), were analyzed using ECG of 30 sec each before and after events.Recording segments with movement or other noise, arousal, and REMsleep were excluded.

Result: LF after right-sided interictal events significantly decreased ascompared to that before events (p<0.01), and was significantly lower thanthat after left-sided events (p<0.05).

Conclusion: Our data suggest that cardiac sympathetic and parasympa-thetic modulation can abruptly decrease after interictal epileptiformactivities in right temporal lobe.

p428EPILEPSIA PARTIALIS CONTINUA IN CHRONIC ANDACUTE CEREBRAL DISEASE: REPORT OF TWOPATIENTSJ. M. Pinzon, P. A. Ruiz, J. J. Ortega, E. Canovas, A. D. Ghinea,and M. De EntrambasaguasHospital General De Castellon, Castellon De La Plana, Spain

Purpose: Epilepsia partialis continua, described in 1894 by Kozhevni-kov, defined as a syndrome characterized by continuous, rhythmic mus-cular contraction affecting limited part of the body for periods of hours,days or weeks. We found a close relationship with electroencephalogramand MRI findings that support the diagnosis, evolution and localizationof clinic.

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Method: A 41 year old female patient who present myoclonic jerks inleft hemifacial in diagnosis of Multiple Sclerosis. A 84 years old femalepatient, which present myoclonic jerks in left hand in context of a vascu-lar lesion. Both women with electroencephalogram and MRI, presentlesion related with the clinic.

Result: Patient 1 was a 41 year-old woman with recurring dysarthria anddysphagia for 10 years and negative studies, who was diagnosed of neu-rological deficit of unknown cause. She presented with a generalizedtonic-clonic seizure followed by left hemifacial myoclonic jerks withoutimpaired consciousness. EEG showed PLEDs in center-right parietalregion while MRI revealed lesions suggestive of multiple sclerosis.Patient 2 was an 84 year-old woman that presented with acute confu-sional state followed by continuous myoclonic jerks in her left hand.EEG showed BiPLEDs prevailing in the right hemisphere while CT-scanrevealed frontal bilateral hemorrhage with greater volume in the righthemisphere

Conclusion: EPC is a syndrome that may be caused by different types ofbrain injury, either chronic or acute, such as demyelinating inflammatorydisease or stroke. EEG and MRI findings show a good topographic corre-lation to each other and to symptoms as well.

p429THE ROLE OF STREPTOCOCCAL INFECTION INCHILDREN WITH NEUROPSYCHIATRIC MANIFESTA-TIONS (PANDAS): A CASE CONTROL STUDYE. Shirazi, S. Noorbakhsh, and F. Ebrahimi TajTehran University of Medical Sciences, Iran, Tehran, Iran

Purpose: To compare the serum antibodies against group A streptococ-cus between cases with OCD &ADHD (pediatric autoimmune psychiat-ric disorders) and control group

Method: A cross sectional/cases control study in peadiatric psychologyclinics in Tehran (Rasoul Hospital) during 2007–2010 had done. Wecompare serum group A streptococcal antibody titers (streptolysin O,deoxyribonuclease B, and Streptokinase) between 79 cases with OCD/ADHD disorder and 39 control group.

Result: Most of cases studied in summer (57%) and spring (23%). Threetype of antibodies were higher in cases (p=0.000). ASOT: cut off level195 had 90% sensitivity; 82% specificity,’ PPV 92%; AUC: (CI= %95;0.99–0.91) Anti streptokinase: cut off level 223 had 82% sensitivity; 82%specificity ‘PPV 95%; AUC: (CI= %95; 0.934–0.735) Anti DNase: cutoff level 140 had 82% sensitivity; 82% specificity ‘PPV 95%; AUC: (CI=%95; 0.99–0.91)

Conclusion: Most of cases studied in summer (57%) and spring (23%)0.3 type of antibodies were higher in cases (p=0.000). ASOT: cut offlevel 195 had 90% sensitivity; 82% specificity,’PPV 92%; AUC: (CI=%95; 0.99–0.91) Anti streptokinase: cut off level 223 had 82% sensitiv-ity; 82% specificity ‘PPV 95%; AUC: (CI= %95; 0.934–0.735) AntiDNase: cut off level 140 had 82% sensitivity; 82% specificity ‘PPV 95%;AUC: (CI= %95; 0.99–0.91)

p430COGNITIVE FUNCTIONS IN PATIENTS WITH FRON-TAL LOBE EPILEPSY DURING TOPIRAMATE ORDEPAKINE THERAPYG. V. Selitskii, and N. SorokinaMoscow Medical Stomatological Unuversity, Moscow, RussianFederation

Purpose: The study was aimed to analyse the cognitive effects of newantiepileptic drugs topamax in patients with symptomatic frontal lobe

epilepsy (left and right-sided epileptic foci) manifested by focal seizureswith secondary generalization as compared with depakine effect and con-trol group.

Method: Three groups of epilepsy patients and control group wereadministered neuropsychological and cognitive tests for psychic andfrontal lobe functions, and others. The 1 and 2 groups included patientswith symptomatic frontal lobe epilepsy with focal secondarily general-ized seizures (left and right-sided foci, 79 and 74 subj.) All patients had amedication change from DPA to TPM. They were free from seizures andhad medium TPM dosage of 200 mg/day. The patients of 3 group had thesame form of epilepsy and had long-term VPA therapy without with-drawn, mean DPA dosage of 400 mg/day (162 subj.). The statistical inter-group comparisons were analysed for all tests. The statisticallysignificant differences on measures of phychic functions and frontal lobeassociated functions were obtained for groups of patients and control.Higher scores in cognitive performance and tests for frontal lobe associ-ated functions were obtained in 1 and 2 TPM groups as compared theVPA group.

Result: Results demonstrate also the more distinct improvement(P<0.01) in patients of the TPM-1 group with left-sided foci in frontalareas as compared the TPM-2 and DPA groups: in scores for temporalordering, sorting of cards, synthesis, depression, planning and controlfunctions, etc.

Conclusion: The results helps to elucidate the contradictory data con-cerning to cognitive effects of topamax.

p431DIFFERENCES OF INTRACEREBRAL ELECTRICALSTIMULATION THRESHOLDS IN THE HUMAN BRAINC. Stephani*, and M. Z. Koubeissi�

*University Medical Center Goettingen, Goettingen, Germany;and �UH Medical Center, Cleveland, USA

Purpose: Differences in threshold current intensities between corticalsurface and intracortical stimulation have been recognized repeatedly.We additionally demonstrate differences between cortical and subcorti-cal stimulation thresholds in humans.

Method: 5 female patients (mean age 40.2 years) with intractablefocal epilepsy underwent invasive presurgical epilepsy monitoring.Three depth electrodes with 10–12 electrode contacts each wereimplanted tangentially into the patients’ insular lobes (2 left, 2 right, 1bilateral) leaving half of the electrode contacts on average in thewhite matter above the insula. Electrode contacts were stimulatedelectrically until a clinical response was produced (current intensity1.5–14 mA, frequency 50 Hz, pulse width 0.3 msec, and train duration3–5 seconds). For localization of electrode contacts, postsurgical cra-nial computer-tomography was superimposed onto presurgical mag-netic resonance imaging using fiducial markers (Software: iplan-stereotaxy 2.6�).

Result: 118 electrodes contacts elicited reproducible symptoms uponelectrical stimulation in the absence of afterdischarges. The mean stimu-lation threshold of 45 electrode contacts clearly located in grey matter(9€2 mA), which produced somatosensory, viscerosensory and gustatoryresponses was significantly higher than that of the 48 electrode contactslocated in the white matter (5.2€2.9 mA), which produced somatosensoryor motor symptoms (t-test: p = 6.98 -11).

Conclusion: Stimulation thresholds necessary to induce symptoms ininsular grey matter are significantly higher compared to stimulationthresholds in the suprainsular white matter. This may be due to a concom-itant counteractivation of inhibitory as well as excitatory neuronal ele-ments with intracortical stimulation which we do not expect in case ofsubcortical stimulation.

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p432THALAMOCORTICAL DYSRHYTHMIA IN PHOTO-SENSITIVE EPILEPSYD. Brazzo*, G. Di Lorenzo�, and S. Seri**Aston University, Birmingham, UK; and �University of Rome‘‘Tor Vergata’’, Rome, Italy

Purpose: To provide experimental support to the hypothesis of a possi-ble disruption in the physiological thalamic regulation of cortico-corticalsynchronisation - thalamocortical dysrhythmia (TCD) - in the pathophys-iology of photosensitive epilepsy (PSE).

Method: 16 subjects, 8 with PSE and 8 healthy volunteers (CTR) withno history of neurological disorders entered the study. Data was acquiredwith a 128-channel dense array EEG and a 306 sensor MEG. Horizontalstationary sinusoidal gratings with spatial frequency of 3 cycles perdegree (cpd) were presented for a 4 sec ‘‘on’’ period, followed by a 4 sec‘‘off’’ period during which a full field equiluminant screen was shown.Independent Component Analysis (ICA) and time-frequency analysis ofthe extracted components were carried out, followed by cluster analysison the components map.

Result: Clusters of components with clear dipolar pattern in the occipitalregion exhibited the following features: 1- evoked and induced gammaband (25–60 Hz) in PSE and CTR groups, without statistically significantdifferences between the two groups; 2- sustained desynchronisation inthe alpha- beta bands (8–20 Hz) only in the CTR group; 3- statisticallysignificant phase locked and sustained synchronisation (power increase)in the theta band (4–8 Hz) in the PSE group.

Conclusion: Abnormal theta synchronisation can be interpreted asthe electrophysiological correlate of disordered connection betweenthalamus and occipital cortex in PSE, in line with TCD model.TCD rather than a syndrome, as proposed in several studies, couldbe a shared mechanism in a number of pathological conditionsincluding PSE.

p433IMAGING DYNAMIC MEMORY ENCODING NET-WORK PLASTICITY POST ANTERIOR TEMPORALLOBE RESECTION FOR REFRACTORY TEMPORALLOBE EPILEPSYM. K. Sidhu*, J. Stretton�, G. P. Winston�, S. Bonelli�,M. Symms�, P. J. Thompson�, M. Koepp�, and J. Duncan�

*Epilepsy Society MRI Unit & UCL Institute of Neurology,London, UK; �UCL, London, UK; and �Institute of Neurology,London, UK

Purpose: An intact fronto-temporal interaction is necessary for success-ful memory encoding. Patients with TLE have a material specific epi-sodic memory loss that can be compounded by anterior temporal loberesection (ATLR). We investigated the episodic memory network in leftTLE (LTLE) patients pre and post ATLR to determine plasticity of thenetwork.

Method: 13 patients with unilateral LTLE performed an fMRI mem-ory encoding paradigm of words and faces preoperatively (pre-op) and4 and 12 months post standard ATLR (post-op). 13 controls werescanned at equal intervals to patients. fMRI analysis was performedwith SPM8.

Result: Preoperative Word encoding: controls activated the left pre-frontal cortex (PFC) and hippocampus (HC) whilst LTLE patientsshowed additional right PFC and HC activation. Face encoding: controlsactivated the right PFC and bilateral HC whilst LHS patients showedright PFC and HC activations only. Postoperative No material specificeffect was seen therefore faces and words analyses were combined. 4

months post-op - pre-op: significant increase in right PFC activity witha significant reduction in bilateral HC activation was seen in patientscompared to controls. 12 months post-op - pre-op: significant increasein bilateral posterior hippocampal activation (predominantly right) witha significant decrease in left PFC activation was seen in patients com-pared to controls.

Conclusion: The memory encoding network following L ATLR dis-plays dynamic plasticity effects. By 4 months a relative increase of rightPFC activation and suppression of HC activation is observed. Subsequentto this period, re-emergence of HC activity occurs bilaterally with dimi-nution of left PFC activation.

p434FUNCTIONAL AND STRUCTURAL CONNECTIVITYOF WORKING MEMORY NETWORKS IN TEMPORALLOBE EPILEPSYG. P. Winston*, J. Stretton*, M. K. Sidhu*, C. Vollmar�,M. Symms*, P. J. Thompson�, and J. Duncan**Epilepsy Society MRI Unit & UCL Institute of Neurology,London, UK; �University of Munich, Munich, Germany; and�UCL Institute of Neurology, London, UK

Purpose: To determine the underlying network architecture of disruptedworking memory (WM) networks in temporal lobe epilepsy (TLE) usingfunctional and structural connectivity analyses.

Method: 84 subjects (30 controls, 30 LHS, 24 RHS) underwent visuo-spatial WM fMRI and DTI. fMRI revealed six key WM nodes - bilateralMiddle Frontal Gyrus (MFG), Superior Parietal Lobe (SPL) and hippo-campi. Functional connectivity: the extracted time-series from the peakvoxel of each node in each subject was used as a regressor in a furthergeneral linear model fMRI analyses to determine areas functionally cou-pled with each node.

Structural connectivity: tractography was seeded from the segmentednodes in each subject and the total volume of connectivity was deter-mined for each subject.

Result: Functional connectivity In LHS, seeding from the bilateral SPLand left MFG showed increased connectivity to the left hippocampus. InRHS, seeding from bilateral MFG and SPL showed increased connectiv-ity to the right post-central gyrus. Seeding from the hippocampi, bothLHS and RHS showed increased temporo-temporal connectivity bilater-ally. Structural connectivity In LHS and RHS, there was an increased vol-ume of connectivity from the ipsilateral SPL and hippocampus with atrend to increase on the contralateral side.

Conclusion: In a task which requires the activation of the fronto-parietalnodes and simultaneous deactivation of the hippocampus, LHS patientsshow increased functional and structural coupling between parietal andtemporal nodes. RHS patients exhibit a similar pattern structurally butwith increased functional connectivity to right central motor regions.Together these results indicate hyperconnectivity of the fronto-parieto-temporal WM network in TLE.

p435MECHANISM OF ACTION OF VAGAL NERVE STIMU-LATION; EVIDENCE FOR ACUTE ANTI-SEIZUREAFFECTC. Mcgrane, F. Kazi, L. Flores, K. N. Ramesha, C. Quelly,M. P. Richardson, C. E. Polkey, and R. D. ElwesKings College Hospital, London, UK

Purpose: To assess whether vagal nerve stimulation (VNS) acutelyaffects the frequency or duration of electrical seizures in adults.

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Method: Nine adult patients with frequent electrical seizures (usuallyfast activity) were identified from the cases attending the VNS clinic atKing's College Hospital. The frequency and duration of ictal activity wasmeasured by visual inspection of the raw EEG during prolonged monitor-ing. Total numbers of seizures and ictal activity in seconds per minutewere compared during a minimum of 10 on/off cycles. Statistical signifi-cance was assessed using non parametric tests for paired and unpairedobservations.

Result: All cases showed a reduction in mean seizure duration during onperiods compared to off periods of VNS. The reduction ranged from 6%to 33% in 4 cases (not significant.) In a further five the reduction rangedfrom 63% to 99% (p=0.001 to p=0.004). Seizure frequency during on anoff periods showed either small increases or decreases, none of whichreached significance; one patient had a total of 12 seizures during 72 on/off cycles in which 11 occurred during off periods.

Conclusion: In a selected group of patients with frequent electrical sei-zures VNS on periods were associated with reduction in mean seizureduration in all cases, which was marked in five. Seizure frequency wasnot affected. The changes suggest that neural stimulation may acutelyalter mechanisms of seizure spread or termination.


p436THE SIGNIFICANCE OF INTRA-STIMULATION DIS-CHARGES DURING NEUROPHYSIOLOGIC LAN-GUAGE MAPPING FOR EPILEPSY SURGERYI. Karakis*, B. Leeman�, C. Leveroni*, R. R. Kilbride*, S. Cash*,E. N. Eskandar*, and M. V. Simon**Massachusetts General Hospital, Harvard Medical School,Boston, MA, USA; and �Emory University, Atlanta, GA, USA

Purpose: Intra-stimulation discharges (IDs) can occur during languagemapping via low frequency electrical stimulation. They are largelyunrecognized due to the significant stimulus artifact associated withthis method, and may precede the occurrence of after-discharges(ADs). The latter can self-propagate beyond the stimulation epoch andorganize in seizures. This study intends to identify predictors of IDsoccurrence and determine whether the latter increases the probabilityof triggered ADs.

Method: 333 stimulation events performed during language map-ping, were analyzed in 3 patients who underwent intracranial EEGrecording. IDs were identified in 77 events. Multivariate logisticregression analysis was used to study the relationship of IDs relativeto the stimulus current intensity, stimulation duration, its lobar loca-tion and its proximity to regions of abnormal cortical excitability(as characterized by presence and frequency of baseline epileptiformdischarges-BEDs).

Result: Presence of BEDs in close proximity to stimulation, increase instimulus intensity by 1 mA and in stimulation duration by 1 second inde-pendently increase the odds of triggering IDs 7.4 times (OR=7.4, CI95[2.83, 19.33], p<0.0001), 1.37 times (OR=1.37, CI95 [1.18, 1.57],p<0.0001) and 1.39 times (OR=1.39, CI95 [1.19, 1.62], p<0.0001)respectively. Higher frequency of BEDs and lobar location of stimulationhave no effect. Occurrence of IDs increases the odds of triggering ADs 5times (OR=5.02, CI95 [2.47, 10.2], p<0.0001).

Conclusion: Longer stimulations, higher currents and presence of BEDsat the stimulation site, increase the probability of IDs occurrence. The lat-ter increases the probability of triggering ADs. Attention to IDs mayimprove safety and precision of neurophysiologic mapping.

p437SLEEP IN PARTIAL EPILEPSY (PE) AS COMPARED TOIDIOPATHIC GENERALISED EPILEPSY (IGE)J. M. Boserio*, R. Bradbury*, Z. Thayer*, Z. Fitzgerald�, andA. Mohamed�

*Royal Prince Alfred Hospital, Sydney, NSW, Australia;�Macquarie University, Sydney, Australia; and �University ofSydney, Sydney, NSW, Australia

Purpose: The current study aims to compare sleep variables in patientswith PE and IGE.

Method: We retrospectively reviewed 22 patients with epilepsy whounderwent prolonged Ambulatory EEG (AEEG) for 4 consecutive nights,from August 2009 – July 2010. A 21 channel EEG and ECG was per-formed according to the 10–20 system. Sleep was scored over the first 24hour period by three trained EEG technicians using Profusion PSG3 soft-ware (Abbotsford, Australia) based on the updated American Academyof Sleep Medicine Manual for Scoring Sleep and Associated Events(Iber, Ancoli-Israel, Chesson and Quan, 2007). All subjects were outpa-tients with stable doses of medications. Patients were grouped as thosewith PE (n=15) or IGE (n=7). We measured durations of Stages I-IVNREM sleep, duration of REM sleep, daytime naps, inter-ictal epilepti-form discharges (IEDs) during sleep and sleep efficiency. The IEDs insleep were counted and grouped into zero, infrequent (<10 in sleep) andfrequent (‡10 in sleep). Chi squared analysis and one-way ANOVA wascarried out using PASW Statistics version 18.0.

Result: We found no strong relationships between the measured sleepvariables when comparing patients with PE vs IGE. The average sleepefficiency was 85% and 89% for the groups respectively (p=0.4) which iswithin normal limits. The duration of Stage IV NREM sleep was signifi-cantly longer in patients with IGE (f=4.4, df 1, p=0.05).

Conclusion: In our cohort, there were no significant differences in themeasured sleep variables and sleep efficiency in patients with PE vs IGE.

p438AFTER-DISCHARGE GENERATION AND TERMINA-TION DURING FUNCTIONAL STIMULATION IN CHIL-DRENJ. Pocock*, H. Cross*, S. Boyd�, W. F. Harkness�, andR. M. Pressler�

*Great Ormond Street Hospital for Children NHS Trust,London, UK; and �Great Ormond Street Hospital for Children,London, UK

Purpose: Functional cortical stimulation (CS) during invasive pre-sur-gical evaluation for epilepsy surgery is used for clinical localization pur-poses but can generate afterdischarges, which may evolve into clinicalseizures. Brief pulses of stimulation (BPS) can terminate afterdischargesin adults. The aim of this study was to evaluate the effectiveness andsafety of BPS in children.

Method: Children undergoing CS with subdural electrodes were moni-tored for afterdischarges. BPS were administered within 1–3 sec ofoccurrence at primary side (same intensity and electrical characteristics,same pair of electrodes as CS, reduced duration of 0.5 sec). Duration ofafterdischarges were compared to a control group (no-BPS) using sur-vival curve analysis and log-rank test.

Result: Afterdischarges and effect of BPS were analysed in 14 children(14 in the BPS and 7 in the no-BPS group). A total of 5005 stimulationswere carried out, provoking trains of afterdischarges in 17.5% in the BPSgroup and 17.5% in the no-BPS group. These provoked clinical seizuresin 0.6% of afterdischarges. A total of 597 BPSs were administered to ter-minate afterdischarges in addition to 97 BPSs given inadvertently. BPS

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proved no seizures or any other adverse reactions. BPS reduced post-BPSduration of afterdischarges significantly (p less then 0.001) in compari-son with the control group

Conclusion: Brief pulse stimulation is a safe and effective method interminating afterdischarges generated by cortical stimulation in childrenundergoing invasive monitoring.

p439HOW FREQUENT ARE ADDITIONAL EPILEPTO-GENIC ABNORMALITIES DETECTED?: INPATIENTLONG-TERM EEG MONITORING VS. OUT-PATIENTEEGK. A. Siddiqui, E. Khalid, and S. SinhaNational Neurosciences Institute, King Fahad Medical City,Riyadh, Saudi Arabia

Purpose: Out-patient EEG (opEEG) study, which is of duration of <1hour, is about 30–50% sensitive in picking up epileptogenic abnormali-ties. Even if they pick up abnormalities, still it is possible that the patientmay have additional abnormalities that can affect the diagnosis and sub-sequent management of the patient. We intend to study the frequency ofadditional epileptogenic abnormalities seen with inpatient long-termEEG monitoring (ltEEG) that were not picked by outpatient study.

Method: We obtained data on consecutive patients who were referredwith diagnosis of seizure disorder, and compared their opEEG study per-formed in the EEG lab to ltEEG records from the Epilepsy monitoringunit. We also looked at demographics and mean duration of epilepsy.

Result: Sixty-eight patients, 35 males and 33 females with mean (+ SD)age 24 (+10.5) years and duration of epilepsy 10.3 (+9.6) years wererecruited. In 56% (n=38), ltEEG provided new information as comparedto the opEEG. Amongst these, 17 patients, whose outpatient study wasabnormal, had additional epileptogenic abnormalities on ltEEG. Theseabnormalities were focal (n=15), and generalized discharges (n=2) thatwere not present in the opEEG. Forty four percent (n=30) had similarfindings in both studies.

Conclusion: Long-term EEG revealed 25% additional epileptogenicabnormalities missed by out-patient EEG study that may be useful in clin-ical decision making and optimal management of the patient.

p440THE POSTICTAL STATE IN DAYTIME FRONTALLOBE SEIZURES: EEG AND BEHAVIOURAL CHARAC-TERISTICSK. Whitehead*, H. Millward*, C. Scott*, S. Eriksson*, andB. Diehl�

*National Hospital of Neurology and Neurosurgery, London,UK; and �UCL Institute of Neurology, London, UK

Purpose: To assess postictal sleep following daytime seizures in frontallobe epilepsy (FLE), and presence of additional lateralising features ofthe postictal EEG.

Method: We included patients with unilateral FLE based on semiology,EEG and either presence of a lesion on MRI or intracranial recordings.Seizures with objective clinical signs (loss of awareness, disruption ofbody posture) between 8am and 8pm were included. Postictal EEG analy-sis of one hour was performed and presence of stage II sleep noted.

Result: We included 31 seizures in 20 patients (15 left, 5 right FLE).Seizure semiology was characterised by motor manifestations as mainfeature in 19, and subtle automatisms with alteration of awareness in 12seizures. In 9 seizures (29%) the postictal EEG showed lateralising fea-tures concordant with the ictal onset zone, not seen in the interictal EEG

in 4 seizures and markedly enhanced in 5 seizures. These included:Marked alpha asymmetry in 13% of all seizures, regional slowing in 13%and regional or lateralised epileptiform activity in 10%. In three patients(15%) those were the only lateralising EEG features. In 16 patients atleast one seizure from wakefulness occurred. 6/23 (26%) seizures fromwakefulness were followed by sleep; EEG seizure duration was compara-ble whether sleep occurred or not (26 vs 29s).

Conclusion: Careful EEG analysis of the postictal state added uniqueinformation in a significant number of patients and should be exploredsystematically in this challenging group. Even daytime seizures are fol-lowed by postictal sleep in a significant proportion, adding to disruptionof daytime activities.

p441PRELIMINARY RESULTS OF VIDEO-EEG FINDINGSIN THE NEURO-INTENSIVE CARE UNIT: IS THERE APROGNOSTIC SIGNIFICANCE IN ACUTE STROKE?N. Dericioglu*, E. M. Arsava�, and M. A. Topcuoglu�

*Hacettepe University Institute of Neurological Sciences andPsychiatry, Ankara, Turkey; and �Hacettepe University,Ankara, Turkey

Purpose: A considerable number of acute stroke patients are followedup in neuro-intensive care units. Epileptiform discharges and non-con-vulsive status epilepticus (NCSE) are not infrequent findings. In ourstudy we aimed to determine the characteristics of EEG findings and thefrequency of NCSE. We also looked whether these findings were corre-lated with the patients’ prognosis.

Method: We analyzed retrospectively the EEG data of patients withischemic stroke (IS) or hemorrhagic stroke (HS), who had video-EEGmonitoring in our center during November 2009-February 2012. EEGfindings were: epileptic discharges (ED), triphasic waves (TW) and fron-tal intermittent rhythmic delta activity (FIRDA). These findings werecorrelated with the patients’ modified Rankin scale (mRS) score at dis-charge.

Result: 41 patients (14 M, 27 F; age: 26–90) were included. 26 patientshad IS, 11 had HS and 4 had IS + HS. EEG findings were: ED in 9 (6 IS, 3HS); TW in 8 (4 IS, 2 HS, 2 IS + HS) and FIRDA in 5 patients (3 IS, 2HS). NCSE was diagnosed in 3 patients (7.3%) (2 IS, 1 HS). At discharge,mRS score was 5–6 in 29 patients. All the EEG characteristics describedabove were detected only in patients with mRS score 5–6. One patientwith NCSE died, in the rest the mRS score was 0 and 5.

Conclusion: ED, TW or FIRDA were detected only in patients with thepoorest prognoses. All the described EEG patterns were present in bothIS and HS. NCSE was rare and did not correlate with outcome.

p442NOONAN'S SYNDROME AND EPILEPSY. NEUROPHYS-IOLOGICAL FINDINGSN. Torres CaÇo, P. Giner Bayarri, K. M. Quintero Hern�ndez,J. Moliner Ib�Çez, R. Faus Cerd�, M. R. Chilet Chilet,A. Mazzillo Ricaurte, M. Escudero Torrella, and S. Garc�aMorenoDr. Peset Hospital, Valencia, Spain

Purpose: Noonan's syndrome is a genetic disorder which was describedin 1963, it has a prevalence of 1/2500 newborns and it is characterized bythe distinctive facial phenotype, cardiac defects, failure to thrive and neu-rological symptoms as cognitive deficit, Arnold Chiari malformation andepilepsy, which is also associated to behavioural and attentional disor-ders. In this study we try to describe the neurophysiological findings andthe characteristics of the seizures in Noonan's syndrome.

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Method: We revise the cases of patients with Noonan's syndrome whichhave been studied in our epilepsy unit and the performed complementaryexplorations.

Result: Epileptic seizures are commonly unnoticed in Noonan's syn-drome, and due to its association with behavioural disorders it is espe-cially important to perform electroencephalograms for the diagnosis andcontrol of the seizures. We present electroencephalogram images inpatients with Noonan's syndrome who present seizures with a poor con-trol, which show focal paroxysmal activity.

Conclusion: The electroencephalogram allows us to find subclinicalparoxysmal activity in patients with this syndrome and helps us toachieve a better clinical management of the patients.

p443INTER- AND INTRA-RATER RELIABILITY OF EEGINTERPRETATION: A LARGE, SINGLE-CENTERSTUDYS. G. Abdel-Baki*, A. Omurtag*, J. Weedon�, C. A. Lushbough�,G. Chari�, E. Koziorynska�, D. Maus�, T. Mcsween�,K. A. Mortati�, A. Reznikov�, V. Arnedo�, and A. C. Grant�

*Bio-Signal Group, Brooklyn, NY, USA; �SUNY DownstateMedical Center, Brooklyn, NY, USA; and �SUNY Downstate,Brooklyn, NY, USA

Purpose: To assess inter-and intra-rater reliability of EEG interpretationutilizing a large sample of heterogeneous EEGs. If EEG reliability is notsufficiently high, the utility of EEG as a diagnostic tool is limited.

Method: We performed a large study of EEG inter- and intra-rater reli-ability. Six board-certified EEGers interpreted 300 representative EEGs(knowing only patient age and medications) divided between two inter-pretation time intervals (T1 and T2), separated by several months. EachEEG was interpreted by 3 readers. Each reader interpreted 100 EEGs atboth T1 and T2, 150 of which were unique. EEGers were unaware that 50EEGs per reader interpreted at T1 were reinterpreted at T2. For eachEEG, readers assigned probabilities to one or more diagnostic categories(normal, status epilepticus, seizure, epileptiform + slowing, epileptiformonly, slowing only, uninterpretable) with one category assigned a higherprobability than any other. Cohen's kappa coefficient (jc) was used tomeasure within-rater agreement.

Result: Intra-rater jc ranged from 0.33 to 0.73 for individual readers,with an aggregated jc of 0.59 (95% CI 0.523 0.653). jc for rater pairs(inter-rater reliability study) ranged from 0.29 to 0.64 with an aggregatedFleiss kappa of 0.44 (95% CI 0.395 0.504).

Conclusion: EEG inter- and intra-RR are in the weak to good range forhighly qualified and experienced EEGers. The subjectivity of EEG inter-pretation may be reduced by establishing consensus interpretation guide-lines, developing statistical prediction rules, and engaging neurologistsin an on-line continuous review of challenging studies with the goal ofachieving consensus interpretations.

Supported by NIH 1RC3NS070658.

p444VAGUS NERVE EVOKED POTENTIAL IN VAGUSNERVE STIMULATION THERAPY -METHOD ANDCLINICAL APPLICATIONK. Usami*, K. Kawai*, M. Sonoo�, and N. Saito�

*The University of Tokyo, Tokyo, Japan; �Teikyo UniversityHospital, Tokyo, Japan; and �The University of Tokyo Hospital,Tokyo, Japan

Purpose: There has been no direct marker to verify the afferent propaga-tion of nerve impulses in vagus nerve stimulation (VNS) Therapy. Weestablished a method for recording the vagus nerve evoked potential

(VN-EP) during implantation of the VNS Therapy system. We discussthe significance of measuring VN-EP in VNS Therapy.

Method: We measured VN-EP in 25 patients who underwent implanta-tion of VNS system. After induction of general anesthesia, scalp EEGelectrodes were set. After placing the VNS lead around the left vagusnerve, VN-EP was recorded while adjusting the stimulation parametersand adjusting the location of the VNS lead on the nerve. Recordings weremade before and after administration of a muscle relaxant.

Result: A reproducible positive peak around 3.4 msec was detected inA1-Cz in all patients, which remained in muscle relaxation. Meanwhileno significant early peaks were detected in A2-Cz, C3-Cz, or C4-Cz. Thelatency of the peak was shortened by moving the lead rostrally. Althoughhigh-amplitude EPs after 10.0 msec were detected in many channels, allsignals disappeared in muscle relaxation.

Conclusion: This study is the first to demonstrate direct evidence ofupward propagation of vagus nerve impulses in the clinical setting withVNS Therapy. The recording of VN-EP provides basic information onelectrophysiological properties of the vagus nerve and serves as confir-matory evidence for appropriate placement of the VNS lead during sur-gery. Furthermore, if the recording in the awake setting is established,they may serve as a surrogate marker of upward stimulation during VNSTherapy.

p445VITRUAL HUMAN PHYSIOLOGY - A SIMULATIONTECHNIQUE TO VISUALISE ICTAL CARDIAC RHYTH-UMS. NarulaPost Graduate Institute of Dental Sciences, Rohtak, India

Purpose: It is proposed to have Virtual Human to facilitate Multi scalemodeling to simulate Pathophysiology of Cardio-Vascular, Respiratoryand Autonomic nervous system by using Software, working station andworkflow.

Method: Several studies have assessed the frequency and character ofictal cardiac rhythm during seizures, and the most compelling evidencederives from the presence of ictal arrhythmias. When ictal cardiorespira-tory variables were recorded in people with epilepsy, an increase in heartrate in 91% of seizures and a transient bradycardia in five seizures (fourpatients) were found. Another study evaluated the eletrocardiographic(ECG) changes during seizures in patients with refractory epilepsy. Thisshowed that 70% of patients had either ECG abnormalities (16%), tachy-cardias (30%), or both (23%) during the ictal and/or post-ictal period.

Result: As it is routinely difficult to perform these investigations, it ishereby proposed virtual human physiology sample as ictal patient toextract information, apply it clinically and prevent complications up toSUDEP

Conclusion: The proposed technique is expected to predict SUDEP inEpileptic Patients.


p446DTI-BASED EVIDENCE FOR IMPAIRED INTEGRITYOF MAJOR WHITE MATTER TRACTS IN NON-LE-SIONAL TEMPORAL LOBE EPILEPSYC. Whelan*, S. Alhusaini*, J. F. M. Meany�, G. Boyle�,A. Fagan�, M. Fitzsimons�, E. O’Hanlon�, C. Doherty�,N. Delanty�, and G. L. Cavalleri*

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*Royal College of Surgeons in Ireland, Dublin 2, Ireland; �St.James's Hospital, Dublin 8, Ireland; and �Beaumont Hospital,Dublin 9, Ireland

Purpose: Here we employ a series of diffusion tensor imaging (DTI)techniques to investigate, using a case/control design, potential structuralchanges within six major white matter tracts of the brain in non-lesionaltemporal lobe epielpsy (nl-TLE). The tracts studied were the corpuscallosum, superior and inferior longitudinal fasciculi, anterior commis-sure, corticospinal tract and uncinate fasciculus.

Method: Scans were acquired using a 3 Tesla Phillips Achieva platformat St. James's Hospital, Dublin and processed using two software pack-ages: Explore DTI (to apply deterministic fiber tractography to our data)and Tract-Based Spatial Statistics (TBSS - a voxelwise, permutation-based algorithm which measures fractional anisotropy (FA)).

Result: Deterministic tractography using ExploreDTI revealed signifi-cant thinning of the white matter fibers of the corpus callosum in nl-TLEpatients (p<0.005; Bonferroni-corrected), in addition to significantreductions in the length and volume of uncinate fasciculus fibers in nl-TLE (p<0.05; Bonferroni-corrected). Tractography further revealed sig-nificant FA reductions in the uncinate fasciculus, left superior longitun-dal fasciculus, right inferior longitudinal fasciculus and anterior corpuscallosum of nl-TLE patients compared to healthy controls (p<0.05; Bon-ferroni-corrected). TBSS results confirmed these FA reductions – illus-trating significantly impaired white matter integrity in widespreadregions of the left superior and right inferior longitudinal fasicucli andgenu of the corpus callosum; with additional FA reductions in the corti-cospinal tract, somatosensory cortex and thalamus (p<0.05).

Conclusion: Detected white matter changes in non-lesional temporallobe epilepsy patients may be related to brain malformations leading tothe development of epilepsy, or alternatively could be secondary to sei-zure generalization/propagation.

p447THE IOWA GAMBLING TASK IN JUVENILE MYO-CLONIC EPILEPSYB. Wandschneider*, M. Centeno*, C. Vollmar�,J. O’Muircheartaigh�, A. Haag*, J. Stretton*, V. Kumari�,B. Schmitz§, G. J. Barker�, M. P. Richardson�, P. J. Thompson*,J. Duncan*, and M. Koepp**UCL Institute of Neurology, London, UK; �University ofMunich, Munich, Germany; �King's College London, London,UK; and §Vivantes Humboldt Klinikum, Berlin, Germany

Purpose: Patients with Juvenile Myoclonic Epilepsy (JME) are thoughtto be impulsive, unable to learn from previous experience, and often pres-ent with risk-taking behaviour, suggestive of frontal lobe dysfunction.We investigated impulsivity in JME and healthy controls using the IowaGambling Task (IGT) to characterize decision-making behaviour.

Method: 21 JME patients and 11 controls, comparable for gender andverbal IQ, were assessed with the IGT. Subjects chose from four decks ofcards with a total 100 cards split into five blocks of 20 (deck A and Bindicative of high risk, C and D of low risk behaviour). A correlation ofIGT performance and network activation during a functional MRI (fMRI)working memory task was performed with SPM-5.

Result: Advantageous minus disadvantageous choices (C+D-[A+B])were established. Both groups learned throughout the task (last versusfirst block: JME: p=0.001; controls: p=0.009). Post-hoc analysis revealedmore learners in the seizure-free group (Pearsons Chi-square p=0.040).In controls, poorer IGT performance was associated with decreased deac-tivation of the default mode network. In JME, poorer performance wasassociated with increased pre-frontal cortex activation (p<0.001uncorrected).

Conclusion: This study provides evidence for impaired experience-related learning in JME patients still suffering from seizures. Noneof our patients experienced any seizures during testing, which sug-gests that inter-ictal, or seizure-related network dysfunction mightimpair the ability to learn. FMRI points to hyperactivity of the dor-solateral prefrontal cortex as the neuroanatomical correlate of thisdysfunction.

p448NON-INVASIVE LANGUAGE MAPPING IN EPILEPTICSAND IN BRAIN TUMOR PATIENTSM. Genetti, F. Grouiller, S. Vulliemoz, L. Spinelli, M. Seeck,C. Michel, and K. SchallerUniversity Hospital of Geneva, Geneva, Switzerland

Purpose: To establish a single, short functional MRI (fMRI) task thatreliably localizes crucial language areas in individual patients.

Method: fMRI was measured during a 8-minute auditory semantic deci-sion task in 18 subsequently operated patients suffering from focal epi-lepsy or from brain tumor as well as in 28 healthy controls. Group andindividual analyses were performed and compared to the Wada test, elec-trocortical stimulation and post-surgical language outcome.

Result: The group analysis revealed a lateralization index of 82 forthe controls and 46 for the patients. In the controls, BOLD clustersconcordant with Broca and Wernicke's areas were activated in 96%and 89% respectively using very conservative thresholding. Activationwas more heterogeneous in the patients but Broca and Wernicke'sareas were still activated in 83% and 89% of the patients, respectively.fMRI results overlapped with electrocortical stimulation in threeimplanted patients and with the Wada test in all patients in whom itwas performed. Transient post-surgical language deficits were found inpatients in whom surgery was performed in the vicinity of the fMRIactivations or who had post-surgical complications implicating areas offMRI activations.

Conclusion: The proposed fast fMRI language protocol not only cor-rectly lateralized, but reliably localized the most relevant language areasin individual subjects. It offers increased security during surgical plan-ning and during image-guided resection of epileptogenic foci, and ofbrain tumors.

p449BRAIN P-GLYCOPROTEIN FUNCTION STUDIED INRATS WITH TWO NOVEL PET RADIOTRACERS:[11C]QUINIDINE AND [11C]LANIQUIDAR. DIFFER-ENCES BETWEEN CONTROLS AND EPILEPTICRESPONDERS AND NON-RESPONDERSR. A. Voskuyl*, S. Syvnen�, V. Russmann�, J. Verbeek§,J. Eriksson§, R. Schuit§, A. D. Windhorst§, M. Labots�,M. Rongen§, A. A. Lammertsma§, E. C. De Lange�, andH. Potschka�

*SEIN – Epilepsy Institutes of The Netherlands Foundation,Heemstede, The Netherlands; �Leiden/Amsterdam Center forDrug Research, Leiden, The Netherlands; �Ludwig-Maximilians-University, M�nchen, Germany; and §VU MedicalCenter, Amsterdam, The Netherlands

Purpose: To characterize brain pharmacokinetics of P-gp substrate[11C]quinidine and P-gp inhibitor [11C]laniquidar in naive rats and in achronic rat model of epilepsy, before and after treatment with P-gp inhib-itor tariquidar.

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Method: Twenty-two rats, divided into controls, responders and non-responders to phenobarbital, underwent scans with both [11C]quinidineand [11C]laniquidar of 45 minutes duration each. All rats were treatedwith 15 mg/kg tariquidar before a second scan with both radiotracers.Brain pharmacokinetics were studied using Logan graphical analysiswith plasma input to yield estimates of VT (brain-to-blood partition coef-ficient).

Result: [11C]quinidine and [11C]laniquidar brain concentrations werevery low at baseline. After tariquidar treatment the concentrationsincreased 3-fold and 9-fold for [11C]quinidine and [11C]laniquidar. VT

estimates of [11C]quinidine, were 0.8 mLÆ mL-1Æ min-1 and 3 mLÆ mL-1Æmin-1 before and after P-gp inhibition. [11C]quinidine concentrationswere higher in non-responders than controls and responders, while[11C]laniquidar brain concentrations where increased in epileptic animalscompared to controls. [11C]quinidine metabolised fast: 25 minutes afterinjection only 15% and 21% of intact [11C]quinidine was present in brainand plasma. For [11C]laniquidar these values were 55% and >75%.

Conclusion: Both [11C]quinidine and [11C]laniquidar brain concentra-tions increased after tariquidar treatment. Although described as inhibi-tor, [11C]laniquidar appeared to be a strong P-gp substrate. Epilepsyhad only a small influence on brain concentrations of both radiotracers.Intriguingly, previous studies with quinidine showed that total brainconcentration in epileptic rats increased 40-fold after tariquidar, sug-gesting a complex P-gp sensitive redistribution after brain entry in epi-leptic rats.

p450ASSESSMENT OF NAMING IN TEMPORAL LOBE EPI-LEPSY PATIENTS: A COMPARISON OF AUDITORYAND VISUAL CONFRONTATION TESTSM. Elisak, J. Amlerova, P. Marusic, and A. Javurkova2nd Faculty of Medicine, Charles University in Prague,University Hospital Motol, Prague, Czech Republic

Purpose: The impairment of naming in patients with left temporal lobeepilepsy (TLE) has been well described. Boston Naming Test based onvisual confrontation is used as a gold standard; Auditory Naming Test isperformed less frequently. The aim of our study was to compare theresults of auditory and visual confrontation naming tests in TLE patients.

Method: We investigated 20 adult patients with unilateral refractoryTLE (mean age 40 years; FSIQ 99 [range 75 to 122]; 10 left- and 10right-sided). Both naming tests (Czech versions) were performed andobtained scores were categorized as normal or abnormal (failed). The cutoff values were calculated from a control group study.

Result: Seven (7/10) left-sided and 2/10 right-sided TLE patients failedBoston Naming Test compared to 6/10 left-sided and 4/10 right-sidedwho failed Auditory Naming Test. Scores from both tests strongly corre-lated (p =0.001), however on individual basis in three patients the resultswere contradictory.

Conclusion: Strong correlation was found between the results of BostonNaming Test and Auditory Naming Test. However in individual patientsassessment of naming can vary according to the test used. Boston NamingTest seems to have better lateralizing value.

p451SEIZURES CAPTURED WITH VIDEO-ELECTROEN-CEPHALOGRAM IN INFANTS WITH EPILEPSYJ. Liao, L. Song, and Y. ChenShenzhen Children's Hospital, Shenzhen, China

Purpose: To investigate the seizure types seen in infants.

Method: Design: Retrospective review. We analyzed all the seizureevents captured with video-encephalogram (video-EEG) over a 6-yearperiod at Shenzhen Children's Hospital.

Result: There were 1000 patients under two years of age with suspectedepileptic events captured with video-EEG. The seizure types were as fol-lows: generalized seizures (including tonic-clonic seizures (n=11), myo-clonic seizures (n=31)), epileptic spasms (n=348, with hypsarrhythmia),focal seizures (n=231, the prominent manifestations were reduced or nomovement with staring and other seizure types that included simple auto-matisms and mild convulsive seizures), status epilepticus (n=7, withduration of 30 minutes or longer), non-epileptic events (n=370, the prom-inent manifestations were slight shaking or whole body rigidity for aboutone second, the EEG showed movement artifact or no backgroundchanges) and complex seizures (n=9, EEG showed one seizure type trans-ferred into another type in one event).

Conclusion: Video-EEG monitoring is helpful in the classification ofseizures in infants with epilepsy. Epileptic spasms and focal seizures aremain seizure types in infants younger than two years old. They must bedifferentiated from non-epileptic events as these are also common.

p452ANALYSIS OF TEMPORAL LOBE EPILEPSY PATHO-GENESIS USING DIPOLE SOURCE IMAGINGL. E. Betting, P. I. A. M. Silva, A. C. Taborda, and R. G. FonsecaFaculdade de Medicina de Botucatu - UNESP, Botucatu, Brazil

Purpose: Mesial temporal lobe epilepsy (mTLE) associated with hippo-campal sclerosis is the most common form of temporal lobe epilepsy. Itsmechanism is not restricted to the amygdalo-hippocampal system. Theobjective of this study was to investigate features of temporal epilepti-form discharges using quantitative EEG in three situations: mTLE,mTLE with dual pathology and mild mTLE.

Method: Subjects underwent routine EEG which was performedaccording to previous recommendations. EEGLAB software was usedfor EEG processing and analysis. All epileptiform discharges wereselected and stored. Discharges were submitted to decomposition byindependent component analysis. For dipole fitting a spherical four-shellhead model and nonlinear adjustment were used. A single equivalentdipole source model was calculated for each component. To identifycommon patterns of discharge propagation cluster analysis of the equiva-lent dipole obtained for each component was used. Closely located dipolesources were classified into same subsets (clusters).

Result: Refractory mTLE: 9 patients (7 women, mean age 45€10). 92discharges evaluated. Source analysis showed the main independentcomponent clusters (ICC) centroids in the hippocampus, cingulate gyrus,fusiform gyrus and frontal lobe. mTLE with dual pathology: 6 patients (4women, mean age 52€13). 35 discharges evaluated. ICC centroids werein the hippocampus, insula, cingulate gyrus and fusiform gyrus. MildmTLE: 3 patients (0 women, mean age 37€15). 11 discharges evaluated.ICC centroids were in the insula, superior temporal gyrus and cingulategyrus.

Conclusion: We confirmed involvement of extrahippocampal regionsin mTLE. Furthermore, patients with different forms of mTLE have dis-tinct networks involved in the pathophysiology of the disease.

p453BLINK REFLEX AT ANTICONVULSIVE THERAPYEFFICACY ESTIMATIONV. Semashko*, V. Kistsen�, and V. Evstigneev�

*BelMAPGA, Minsk, Belarus; and �Belarussian MedicalAcademy of Postgraduate Education, Minsk, Belarus

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Purpose: The aim of our study is to estimate the self-descriptiveness ofBlink Reflex (BR) as a predictor of epilepsy behavior character (exacer-bation or remission) and treatment efficacy.

Method: Thirty patients (mean age 35.4€2.9 years) with temporal epi-lepsy were studied. Blink Reflex was evoked by electric supraorbitalstimulus. Latency, duration, amplitude of R1, R2 components and R3presences were evaluated.

Result: Hyperexcitable BR type presented in 18 (60%) of patientsbefore anticonvulsive therapy. That BR type characterizes: 1). early R1appearance; 2). prolongation of R1 and R2 duration; 3). R2 polyphasyand high amplitude; 4). R3 presence. Seven patients (23.5%) had normalBR, others - hypoexcitable. We observed all patients every 4 weeks dur-ing 3 months with seizure frequency registration and electroencephalog-raphy (EEG) control. High seizure frequency correlates with early R1appearance (r=0.57, p=0.042), prolongation of R2 duration (r=0.55,p=0.049) and R3 presence (r=0.7, p=0.006). During anticonvulsive ther-apy most R2 duration reduction was obtained in subgroup of patientswhose took depakine with topiramate (r=0.74, p=0.003). BR type and itsparameters normalization have not correlations with brain damage locali-zation (neocortical dysplasia or mesial temporal sclerosis) and epilepti-form discharge occurrence in EEG. Before seizure reduction R3component was registered in focus side at 100% cases.

Conclusion: Complex Blink Reflex parameters (R1 latency, R2 dura-tion and R3 presence) can be use to estimate prognosis of anticonvulsivetherapy efficacy.

p454THE SCN1A-PLOYMORPHISM AND CARBAMAZE-PINE - EFFECTS ON CORTICAL EXCITABILITY INHEALTHY ADULTS IN A TMS-STUDY IN THE EPI-CURE-CONSORTIUMA. Hermsen*, K. Menzler*, P. S. Reif*, K. Balkenhol*,H. Bugiel*, K. M. Klein*, C. Duddek*, H. M. Hamer�,H. Trucks�, T. Sander�, A. Haag*, and F. Rosenow**Philipps-University Marburg, Marburg, Germany; �UniversityHospital Erlangen, Erlangen, Germany; and �Cologne Centerfor Genomics (CCG) Cologne University, Cologne, Germany

Purpose: SCN1A encodes a voltage-gated sodium channel and acts inneuronal depolarization. Mutations lead to various epilepsy syndromes.Studies revealed a correlation between genotype of SCN1A-polymor-phism (IVS5N+5 G->A; dbSNP: rs3812718) and pharmacoresponse toCarbamazepine (CBZ) Transcranial magnetic stimulation (TMS) mea-sures drug induced cortical excitability changes. Purpose:

SNP- effect on cortical excitability as measured by baseline/CBZ-TMS

Method: Genotyping: 272 volunteers, 140 homozygotic (AA: 53.5%,GG: 46.5%). Whole TMS- samples of 92. TMS-parameter: motor evokedpotentials in RMT, interstimulus intervals, cortical silent period (CSP).Offline Analysis. Design: double-blind, randomized, cross-over; two vis-its (TMS at baseline & 5 hours after 400mg CBZ or Placebo p.o.).

Result: No age or sex differences. CBZ (medium level: 4.53 mg/ml)resulted in higher excitability threshold (p=0.001). Genotypes did neitherdiffer in baseline cortical excitability (p=0.290) nor in response to CBZ(p=0.154) as measured by RMT. However, CSP was prolonged afterCBZ for GG and not AA (p=0.015)

Conclusion: We did not find significant baseline differences for thegenotypes. Differential reaction to CBZ was apparent only in CSP; GGwas associated with a higher increase in CSP duration than AA. CSPreflects the function of GABAergic interneurons, which are disturbed infunctional SCN1A disorders. The study shows that pharmacogeneticgroup differences can be proven by TMS.

p455SEIZURE PROPAGATION ANALYSIS VIA SEGMENTA-TION OF ICTAL ELECTROCORTICOGRAPHYS. Pirker*, C. Flamm�, A. Graef�, M. Deistler�, andC. Baumgartner**General Hospital Hietzing with Neurological CenterRosenh�gel and Karl Landstein, Vienna, Austria; and �Institutefor Mathematical Methods in Economics, Vienna University ofTechnology, Vienna, Austria

Purpose: Surface electroencephalography (EEG) is often limited bymovement artifacts, suppression of high frequencies and low spatial reso-lution. Therefore non-invasive recordings do not always reveal a preciseidentification of the seizure onset zone especially in patients with non-le-sional epilepsy. Invasive subdural strip electrodes allow for a better iden-tification of the seizure onset zone. A semi-automatic evaluation of ictalactivity and propagation may support clinicians performing video EEGmonitoring.

Method: Invasive subdural strip electrodes were implanted to record elec-trocorticograms (ECoGs) during video EEG monitoring in a drug-resistantpatient with focal epilepsy. The patient suffered from four seizures duringinvasive recording. A novel software was designed for automatic segmen-tation of individual ECoG channels on the basis of power changes inselected frequency bands. Each segment was evaluated automatically withregard to the predominant frequency. Segments with a predominant thetafrequency were categorized as ictal activity by this program.

Result: Three seizures were analyzed using this novel segmentationmethod. Seizure onset on individual channels as detected with thismethod was well correlated with the visual analysis of ECoGs. In addi-tion, time spread of theta activity on individual channels allowed an eval-uation of seizure propagation.

Conclusion: Our ECoG segmentation method may allow for a faster andmore objective seizure onset detection and description of ictal activitypropagation in ECoG. Knowledge of ictal activity propagation may beuseful for a better prediction of seizure outcome after epilepsy surgery.

Semiology, Aetiology and Classification 11Tuesday, 02 October 2012

p456LONG-LASTING EPILEPSY INDUCES PROGRESSIVECHANGES IN THE BRAIN: EVIDENCE FROM TYPE IIFCD PATIENTSA. Finardi*, F. Colciaghi*, C. Marras*, L. Castana�, P. Nobili*,M. Bramerio�, G. Lorusso�, and G. Battaglia**IRCCS Neurological Institute Carlo Besta, Milano, Italy; and �

Niguarda General Hospital, Milano, Italy

Purpose: To explore whether severe epilepsy is a dynamic pathologicprocess able to induce structural changes in the malformed brain ofpatients affected by type II focal cortical dysplasia (FCD), frequentlycharacterized by severe epilepsy.

Method: We analyzed four pediatric and four adult type II FCD patientssurgically treated for drug-resistant focal epilepsy. In epileptogenic-dys-plastic as well as in adjacent normal-appearing areas we performed care-ful morphologic and morphometric analysis. We also analyzed theNMDA receptor complex composition using protein fractions specifi-cally enriched in post-synaptic densities.

Result: Larger dysmorphic neurons (soma size >1100lm2) were mainlypresent in the epileptogenic areas from type II FCD patients with a longer

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epilepsy history (>10years); we found a strong and statistically signifi-cant positive correlation between the percentage of these neurons andduration of epilepsy (r=0.9; **p<0.01). In the same epileptogenic areasthese data were paralleled by reduced neuronal cell density, statisticallysignificant in deep layers of the cortex (*p<0.05), and by a high degree ofreactive gliosis. Finally, in all considered FCD patients we foundincreased expression of NMDA regulatory subunits in the post-synapticmembranes of dysmorphic neurons; a concomitant increase of NMDAscaffolding protein levels was also present in the post-synaptic fraction ofadult patients.

Conclusion: Our morphometric data support the hypothesis that cellularabnormalities observed in type II FCD epileptic patients could be wors-ened by a long history of severe, repeated seizures and indicate thatabnormalities of NMDA receptor complex and associated proteins areconsistently associated with, and may sustain epileptogenesis of type IIFCD patients.

p457REFRACTORY CONVULSIVE STATUS EPILEPTICUSAS THE FIRST MANIFESTATION OF SYSTEMICLUPUS ERYTHEMATOSUSI. Unterberger, M. Bergmann, M. Prieschl, G. Walser, G. Luef,G. Ratzinger, and N. SeppMedical University Innsbruck, Innsbruck, Austria

Purpose: Refractory status epilepticus (SE) is an uncommon symptomin systemic lupus erythematosus (SLE) despite the case definition of neu-ropsychiatric manifestation of SLE.

Method: A 54-year-old female patient presented with a sudden onset ofrefractory convulsive SE. Conventional antiepileptic drugs failed to con-trol seizures and thiopental anesthesia has been needed for over 100 con-secutive days. Laboratory tests exhibited anaemia (hb 91g/l) andleucopenia (3.0 G/l), routine test for vasculitis was negative. Cerebrospi-nal fluid (CSF) examination showed white blood cell 8/ll, red blood cell33/ll with normal CSF/serum glucose ratio and no oligoclonal bands.Extensive CSF and blood work-up and brain biopsy failed to detect anyviral, bacterial or fungal origin. Initial brain MRI showed marked bilat-eral hippocampal T2 hyperintense signal. Consecutive brain MRIsrevealed marked bilateral hippocampal atrophy and a vascular ischemiclesion in the right basal ganglia. Starting from the first day intravenousacyclovir was administered. Clinically, the patient has been sufferingfrom medically refractory ongoing temporal lobe seizures and severeneuropsychological deficits. Several years later the patient exhibited ageneralized exanthema multiforme. In addition, she reported bilateral legweakness with hypaesthesia, resembling severe axonal neuropathy. Lab-oratory tests showed leucopenia (2.5 G/l), elevation of antinuclear anti-bodies (ANA) (1:1280), anti-ds DNA (1:160), positive RNP/Smantibodies and positive antiphospholipid antibodies.

Result: SLE was diagnosed and treatment with oral corticosteroids(80mg/d) was started with slow tapering to 16mg/d. The patient improvedclinically and laboratory tests showed normalization or marked recovery.

Conclusion: SLE should be considered in unexplained SE, even if initiallaboratory tests are not definitive

p458SEXUAL DISFUNCTIONS, AEDS AND SERIC HOR-MONAL PROFILE IN EPILEPTIC MENL. Zummo, L. Urso, M. Gammino, V. Calabr�, D. Urso, andO. DanieleUniversity of Palermo, Palermo, Italy

Purpose: Sexual Disfunctions (SD) are common in epileptics with aprevalence between 38–71%. Aetiology is multifactorial, due to epilepsy

per s� and AEDs. The aim of the study is to evaluate incidence of SD inepileptic men, type of epilepsy, AEDs, frequency of seizures, seric hor-monal profile and depression.

Method: 61 patients between 18–67 yrs were recruited. 50.8% had idio-patic generalised epilepsy and 49.2% had focal epilepsy (temporal53.3%). 43.5% had frequent seizures. 78.7% were in monotherapy while21.3% on polypharmacy. VPA was the most frequently used AED, aloneor in association with others.

Result: SD had a greater prevalence related to age. There isn't associa-tion between types of epilepsy as well as AEDs and SD (only PB wasslightly significant). No association was found between types of epilepsyand hormonal changes whereas these were found to be correlated toassumption of CBZ. An association was found between the presence ofhormonal changes and SD in epileptics treated with AEDs, but not withorgasmic disfunction. Among all patients 61% showed depressivechanges and there is a correlation between depression and SD as well aschanges of libido and erectile disfunction but not orgasmic.

Conclusion: Our results indicate that there isn't an association betweenthe type of epilepsy and the presence of SD whereas they show an associ-ation between SD, hormonal changes and AEDs. Particularly CBZ andPB should be avoided in pts who present some impairment of sexualfunctions and in olders. Furthermore, the depression in epileptics mayinfluence sexual functions.

p459MEDICAL TREATMENT OF FOCAL CORTICAL DYS-PLASIA: A CASE SERIES OF 11 PATIENTSS. H. Kim, H. W. Ryu, J. H. Lee, B. C. Lim, J. H. Chae,Y. S. Hwang, and K. J. KimSeoul National University Children's Hospital, Seoul, Korea

Purpose: Focal cortical dysplasia is often associated with intractableepilepsy. Outcome after surgical treatment has been evaluated in variousstudies, but the role of medical treatment remains largely unknown. Weretrospectively evaluated the clinical features and long-term outcome in11 patients with focal cortical dysplasia who initially responded well tomedical treatment.

Method: Patients with focal cortical dysplasia who achieved more than2-year seizure freedom with antiepileptic drugs (AED) were analyzed.Clinical, seizure and electroencephalographic (EEG) features were col-lected. Types of AED, time to seizure cessation from commencement ofAED and outcome after discontinuation of AED were assessed.

Result: Eleven patients (age range, 0.5 - 17.3 years) were included.Median seizure free period was 3.6 years (range, 2.2 - 11.4 years). Themedian total number of seizure events before treatment was 6 (range, 2–30). Seizure control was achieved immediately after commencement ofdrugs in 45%, and within 2 months in 91%. Eight (73%) patients obtainedseizure control with the first AED. Seizures responded best to oxcarbaze-pine, which achieved seizure control in 6 patients (55%). Discontinuationwas attempted in 5 patients with a successful outcome in 3 patients. EEGstudies were normal in 5 (45%) patients before treatment, and normal in 8(73%) patients after treatment.

Conclusion: This study suggests that some patients with focal corticaldysplasia may respond well to medical treatment, especially when imme-diate seizure control is achieved with the first AED.

p460GAD65 - GAD67 MRNA AND PV EXPRESSION INHUMAN FOCAL CORTICAL DYSPLASIAV. Medici, L. Rossini, R. Garbelli, L. Tassi, and R. SpreaficoI.R.C.C.S. Foundation Neurological Institute, Milan, Italy

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Purpose: Epileptic tissue is characterized by an imbalance in the net-work activity, and several studies reported that inhibitory function isdamaged in dysplastic tissue. A consistent decrease in the number ofinhibitory interneuronal subsets expressing parvalbumin (PV), in tissueresected from patients with Focal Cortical Dysplasia (FCD) was showed.In order to verify if the decrease of PV protein expression observed inepileptic tissue corresponds to a parallel impairment in GABAergic com-partment, we analyzed 48 surgically treated patients operated on forintractable epilepsy including 38 patients with FCD (type I, II and III)and 10 patients without any visible lesion (cryptogenic). Seven controlcases were also analyzed.

Method: Serial sections were processed using in situ hybridization andimmunocytochemical techniques. Slides were immunostained for GAD-65 and GAD-67 probes and for antibody against PV. The density of inhib-itory PV-immunoreactive interneurons in relation to GABAergic cellswas estimated in controls and in all different pathological groups by usinga two-dimensional cell counting technique.

Result: The density of PV-immunoreactive interneurons was reduced inpathological groups as compared to the controls. However mRNA levelsof GAD-67 and GAD-65 were similar both in control and in FCD cases.Although the PV reduction was observed thought all the cortical thick-ness, layers III and IV, where the protein normally is more expressed,were observed to be particularly affected.

Conclusion: Preliminary results show that in FCD patients PV reductionis not apparently correlated with the mRNA reduction of GAD-65 andGAD-67.

p461THE CLINICAL SPECTRUM OF HEMIMEGALEN-CEPHALY IN CHILDRENF. X. Sanmarti*, M. I. Sigatullina�, J. Campistol*, andS. S. Shamansurov�

*Hospital San Joan De Deu, Barcelona, Spain; and �TashkentInstitute of Postgraduate Medical Education, Tashkent,Uzbekistan

Purpose: To analyze the clinical features of different types of Hemim-egalencephaly

Method: MRI and continuous Video-EEG investigation were performedin 7 patients with Hemimegalencephaly. Evolutionary postoperative fol-low- up of 2 patients with transferred Hemispherectomy was reviewed

Result: 3 patients have an isolated type of Hemimegalencephaly and 4patients a syndromic type, which were associated with ipsilateral hemi-hypertrophy of the whole body. Six patients had seizures (severe refrac-tory epilepsy- 5, febrile seizures-1). The mean age of the epilepsy onsetwas 3, 7 (0, 1–13) months. All patients had a contralateral hemiparesis,generalized hypotonia and developmental delay that went from severe tothe mild degree. The seizure semiology was ranged from febrile seizuresto the polymorphic types, like myoclonic seizures (2), complex partialseizures (3), asymmetric tonic spasms (1) and focal clonic sezures (1). Inall cases a continuous theta and delta activity in the involved hemispherewas registered. In 3 cases registered continuous ‘‘burst-suppression’’ pat-tern in the side of Hemimegalencephalia. In 2 patients with severe pro-gressive epileptic encephalopathy a functional hemispherectomy wasperformed with the result as 90% of seizure reduction in 2 patients. Post-operative hemiparesis in patients was not more severe than that beforesurgery. Cognitive outcome was much better after operation in bothpatients

Conclusion: In most cases, a clear correlation was found between theside of the Hemimegalencephaly and seizure semiology which were alsoconfirmed by the continuous Video-EEG register. Early intervention isimportant to prevent encephalopathy and compromise of function withinthe unaffected hemisphere.

p462M. PNEUMONIAE IN CEREBROSPINAL FLUIDS OFCHILDREN WITH NEUROLOGICAL MANIFESTA-TIONS: A CASE/CONTROL STUDY; TEHRAN, IRANS. Noorbakhsh, V. Zarabi, F. Khodapanahandeh, andA. TabatabaeiTehran University of Medical Sciences, Iran, Tehran, Iran

Purpose: Searching the M. pneumoniae –DNA and antibody (IgG) inCSF of children with neurologic manifestations.

Method: This case control study done in pediatric wards of Rasoul hos-pital in Tehran (2008–2010). The M. pneumonia –DNA and IgG (ELISA)level in CSF samples compared between 55 cases with neurological man-ifestations [mean age: 3.84 € 3.43 years ]; and 10 controls (simple febrileseizure with normal CSF). Chi square values<0.05 were considered sta-tistically significant. Sensitivity; specificity; PPV; NPV for CSF antibodylevel determined by using the Area under the Roc Curve.

Result: Positive M. pneumoniae - DNA detected in the CSF of 1 withGBS (1/53; 2%); Cut off level for antibody was 0.0025, AUC was 0.876(%95 CI, 0.78 –0.96; P Value =0.000); 73% sensitivity; 90% specificity;100% PPV; 28.8% NPV. CSF antibody had significant differencebetween cases and controls [0.08€0.26 vs 0.001€0.001; P value: 0.02,Kappa =0.27). Lowest IgG level reported in cases with aseptic meningitis(without encephalitis); the highest IgG level observed in cases with focalneurologic signs.

Conclusion: Detecting the M. pneumonia-DNA in CSF was rare (2%).IgG level in CSF even in very low amount had 70% sensitivity; 90%specificity and 100% PPV especially in cases with encephalitis, GBS orother focal neurologic signs but not in cases with aseptic meningitis.CSF-IgG test (NPV=28.8%) was weak for ruling out the M. pneumoniaeas the etiologic cause in cases with neurologic manifestations. The posi-tive PCR-DNA in the CSF is more reliable for diagnosing the recent M.pneumonia infection.

p463DATA-DRIVEN PHENOMIC ANALYSIS OF EPILEPTICENCEPHALOPATHY PHENOTYPES USING ANONTOLOGY-BASED PHENOTYPE DATABASEJ. A. Albers*, S. Weckhuysen�, A. Suls�, B. Coessens�,P. N. Robinson§, P. De Jonghe–, C. R. P. Euroepinomics Res**,and I. Helbig**University Medical Center Schleswig Holstein, Kiel, Germany;�University of Antwerp, Antwerp, Belgium; �Cartagenia N.V.,Leuven, Belgium; §Charit� - Universittsmedizin Berlin, Berlin,Germany; –Neurogenetics Group, ANTWERP, Belgium; and**Strassbourg, France

Purpose: Epileptic encephalopathies constitute a phenotypically chal-lenging group of seizure disorders. We aimed to apply novel phenomicstrategies for the characterization of epilepsy phenotypes by combiningan ontology-based phenotype database with data-driven identification ofnovel phenotypic associations.

Method: We constructed a validated epilepsy ontology, which wasimplemented in the Human Phenotype Ontology (HPO) and used as thedata entry matrix the web-based Cartagenia BENCH phenotype platformof the EuroEPINOMICS-RES consortium. The phenotypic data of 86patients with West syndrome, Dravet syndrome, and myoclonic astaticepilepsy were then systematically analyzed for phenotypic similarities,assessing the frequency of combinations of various unique phenotypictraits. Combinations were screened by two expert reviewers for novel orunexpected combinations of epilepsy phenotype traits.

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Result: Phenotypic data analysis revealed 1431 different combinationsof phenotypic traits. 338 of these combinations were annotated at least intwo patients. While most combinations of phenotypic traits were com-mon combinations in the three inserted epilepsy syndromes, we foundthree rare combinations present in at least three patients from differentcenters, which were followed up by refined phenotyping to explore possi-ble subgroups.

Conclusion: Analysis of large-scale phenomic data permits subgroupingof patients with similar epilepsy phenotypes. This clustering may providethe basis for data-driven delineation of novel epilepsy phenotypes in rareepileptic encephalopathies.

p464A DECADE OF EXPERIENCE WITH DEEP BRAINSTIMULATION FOR PATIENTS WITH REFRACTORYMEDIAL TEMPORAL LOBE EPILEPSYM. Sprengers, K. Vonck, E. Carette, A. Meurs, D. Van Roost, andP. A. J. M. BoonGhent University Hospital, Ghent, Belgium

Purpose: To evaluate the long-term results of mesial temporal lobe(MTL) deep brain stimulation (DBS) as an alternative therapy forpatients with MTL epilepsy.

Method: Since 2001, 11 patients with refractory MTL epilepsy under-went MTL DBS. When unilateral MTL DBS failed to decrease seizureswith >90% after 3 years, a switch to bilateral MTL DBS was proposed.

Result: After a mean follow-up of 8.5 years, 6/11 patients have a ‡ 90%seizure frequency reduction with 3/6 seizure free for > 3 years; threepatients have a 40–70% and 2 have a <30% reduction. Best outcome wasfound in patients with a focal unilateral ictal onset. None of the patientsreported permanent symptomatic side effects. Regarding the chronicstimulation protocol, four relevant assessments were made. 1) Augment-ing output voltage mostly did not affect seizure frequency, but in threecases it did. 2) Starting bilateral DBS resulted in improved seizure controlin 3/5 patients. 3) Introducing day-night cycling (DBS off between 0 and6 am) after a stable frequency reduction had been reached did not affectseizure frequency in 4/5 patients. 4) Switching DBS off during at least amonth in 7 patients was associated with an immediate or delayedincreased seizure frequency in 4/7 patients, did not affect seizure fre-quency in 2/7 patients and coincided with seizure freedom in 1/7 patient.

Conclusion: This open study with an extended long-term follow-updemonstrates maintained efficacy of DBS in MTL structures for patientswith refractory medial temporal lobe epilepsy. Bilateral MTL DBS mayherald superior efficacy in unilateral MTL epilepsy.


p465INNOVATED SURGICAL TREATMENT OF EPILEPTICSYNDROME IN PATIENTS WITH BRAIN ARTERIOVE-NOUS MALFORMATIONSV. Panuntsev, L. Rozhchenko, T. Stepanova, V. Aliev, andR. GafurovRussian Polenov Neurosurgical Institute, Saint-Petersburg,Russian Federation

Purpose: To investigate the results of treatment of epileptic syndrome(symptomatic epilepsy) in patients with cerebral arteriovenous malfor-mations (AVM) based on the modernized method of intravascular sur-gery under EEG control.

Method: 42 patients (17–60 aged) with AVMs manifesting with epilep-tic syndrome (frequent severe partial seizures with secondary generaliza-tion) were included in the analysis. All the patients received activeendovascular superselective embolizations of AVMs using Hepas-Sphere� microspheres (BioSphere Medical, France) loaded with anti-convulsant (Diazepam). The treatment involved neurophysiologiccontrol of dynamic EEG monitoring in all stages.

Result: 58 surgeries in 42 patients were performed on the same tech-nique. Total and subtotal AVM embolization was achieved in 29 patientsand partial in 13. Electroclinical observations with catamnesis to 3 yearsshowed a positive postoperative adaptive dynamics of the epileptic syn-drome with a distinct tendency toward inhibition of epileptic manifesta-tions. All the patients had a significant decrease in the frequency andseverity of epileptic seizures, in a number of observations changes in thestructure of seizures, 27 (64%) patients had the attacks completelystopped (Engel class I). EEG proved full regression of paroxysmal activ-ity with a tendency toward normalization of the spatial bioelectrical pat-tern.

Conclusion: The proposed modernized method of active surgical treat-ment of symptomatic epilepsy in patients with cerebral AVM (Hepa-Sphere with anticonvulsant) provides a significant increase in theeffectiveness of treatment through direct targeted delivery of anticonvul-sant immediately into the brain and a creation of its prolonged depot inthe nidus of AVM under the control of EEG monitoring.

p449HIGH-RESOLUTION EEG ELECTRICAL SOURCEIMAGING CONTRIBUTES TO LOCALIZE THE EPILEP-TOGENIC ZONE IN MALFORMATIONS OF CORTICALDEVELOPMENTE. Rikir*, L. Koessler�, M. Gavaret�, J. Jonas§, S. Colnat-Coulbois–, J. Vignal§, H. Vespignani§, and L. Maillard§

*CHU Sart-Tilman, LIEGE, Belgium; �CRAN, Nancy, France;�CHU de la Timone, Marseille, France; §Centre Hospitalier etUniversitaire, Nancy, France; and –CHU de Nancy, Nancy,France

Purpose: Malformations of Cortical Development (MCD) are increas-ingly recognized using MRI and EEG. However, localizing the epilepto-genic zone (EZ) associated with MCD still relies on intra-cranial EEGrecordings. Our purpose was to study the spatial correlations between themodeled electrical sources of inter-ictal events (Interictal Zone = IZ)recorded with High-Resolution scalp EEG (HR-EEG) and the EZ definedby stereo-EEG (SEEG) in MCD.

Method: This prospective, bi-centric study enrolled 21 consecutivepatients (19 in Nancy and 2 in Marseille) with MCD undergoing pre-sur-gical investigations between 2008 and 2011 and comprising a HR-EEG(64-channels) with electrical source imaging and SEEG recordings.

Result: Three patients were excluded from the analysis because ofmissing data. HR-EEG IZ co-localized with the EZ in three cases (2/3were MRI negative). HR-EEG IZ and SEEG EZ were completely ormore often partially overlapping in 94%. In six cases, the HR-EEG IZcomprised the entire EZ and extended to the propagation zone in 4/6.In 4 patients with temporal lobe epilepsy, HR-EEG IZ was completelyincluded into the EZ. In these cases, the HR-EEG IZ missed the med-ial temporal component of the EZ. In 4 cases, HR-EEG IZ partiallyoverlapped the EZ. In 7 patients with negative MRI, HR-EEG cor-rectly localized at least a part of the EZ. In 2/7, it allowed its preciselocalization.

Conclusion: HR-EEG combined with electrical source imaging helps tolocalize and target the EZ associated with established or suspected MCDparticularly in MRI negative cases.

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p449SENSITIVITY OF A 256 CHANNEL EEG RECORDINGIN TEMPORAL MESIAL SCLEROSIS PATIENTS ANDTEMPORAL NEOCORTICAL PATIENTSC. Arcaro, A. Del Felice, E. Formaggio, S. Storti, I. BoscoloGalazzo, R. Mai, A. Fiaschi, and P. ManganottiUniversit degli Studi di Verona, Verona, Italy

Purpose: to describe the augmented sensitivity of a 256 channel EEGrecording in the epileptiform activity scalp localization by visual inspec-tion of patients affected by temporal mesial sclerosis and neocortical tem-poral epilepsy. Exploiting 20 left and 20 right electrodes covering facebetween orbitary floor and the upper margin jaw (anterior and posteriorzygomatic electrodes) we underlie the accuracy and non-invasivity ofthis method.

Method: we recorded a rest 256 channel EEG in 14 patients (7 femaleand 7 male mean age 42 years) affected by temporal epilepsy. We consid-ered six mesial temporal sclerosis patients and three neocortical temporalpatients. We then compared the scalp localization of epileptiform abnor-malities by visual inspection through the standard 10–20 bipolar andmonopolar montages and later through the 256 Topo Plot Average Refer-ence Map e.g. a projection of each electrode's activity on a scalp model.

Result: in temporal mesial sclerosis patients, EEG abnormalitiesobserved in fronto temporal standard 10–20 montage are seen with thehighest negative peak in anterior zygomatic channels (Topo Plot Mapmontage), while temporal neocortical patients underling a large fieldpotential are seen in posterior zygomatic electrodes.

Conclusion: since the basal temporal cortex is tangential to the lateralsurface of the skull and neocortical epilepsy underlies a large field poten-tial, anterior and posterior zygomatic electrodes respectively could beconsidered at the same time as a non-invasive method and specific tool toincrease the maximum peak localization by visual inspection in patientsaffected by temporal mesial sclerosis and temporal neocortical epilepsypatients.

p449THE EVALUATION OF SEXUAL FUNCTIONS AND SEXHORMONES IN MALE AND FEMALE EPILEPSYPATIENTS WHO ARE ON VALPROIC ACID AND CAR-BAMAZEPINE MONOTHERAPYA. Erdal, G. Kutlu, Y. BiÅer Gçmceli, and L. E. InanMinistry of Health, Ankara Research and Training Hospital,Ankara, Turkey

Purpose: In patients with epilepsy, sexual dysfunction is seen at anhigher incidence than in patients with other chronic neurologic diseases.In this study, we examined sex hormone levels and sexual dysfunction inpatients with epilepsy who used carbamazepine (CBZ) and valproic acid(VA) monotheraphy.

Method: There were overall 35 patients in the study; 18 patients whoused VA and 17 patients who used CBZ. These patients’ medical history,epilepsy history, sex hormone levels, drug blood levels, HamiltonDepression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale(HAM-A) and Arizona Sexual Experience Scale (ASES) levels wereexamined.

Result: The rate of sexual dysfunction was found to be higher in womenpatients with epilepsy than men irrespective of drugs, anxiety and depres-sion. Dehydroepiandrostenedionesulphate (DHEAS) and progesterone(PG) levels were found to be higher in male patients who used VA. Freetestesterone (FT) levels were important both for male and female sexual-ity. The number of pregnancies was lower in female patients using VAand we think that it was associated with VA induced hyperandrogenism.

Conclusion: Sexual dysfunction and alterations in sex hormones mayoccur frequently in epilepsy patients. The most significant finding of ourstudy was high rates of sexual dysfunction in women. Further studies arenecessary to support our findings.

p469EPILEPSY AND REPRODUCTIVE DISORDERSI. A. Zhidkova, and T. V. KaznacheevaMoscow State Medical Dental University, Moscow, RussianFederation

Purpose: To determine reproductive endocrine disorders among womenwith epilepsy (WWE), who were long-term treated with antiepilepticdrugs (AED).

Method: Group I included 107 women with epilepsy of reproductive age(mean age 25.6 € 6.2 years). A comparison group II consisted of 47 womenwith polycystic ovary syndrome (PCOS) (mean age 26, 7€ 5.7years). Allwomen were investigated: sex hormones – luteinizing hormone (LG), fol-licle-stimulating hormone (FSH), prolactin (PRL), estradiol (E), progester-on (P), testosterone (T); dynamic ultrasound examinations; evaluationclinical symptoms of hyperandrogenism. The comparative study based ondiagnostic criteria of PCOS, taken in 2003 (The Rotterdam ESHRE/FSRM-Sponsored PCOS consensus of workshop group, 2003).

Result: 73% women with epilepsy were healthy. 27% of WWE fromgroup I had ovary dysfunction; menstrual disorders revealed amongwomen using valproate (VPA, doses > 1200 mg/day) more often thanamong WWE using new AED (lamotrigine (LTG), topiramate, leveti-racetam (LEV), oxcarbazepine). 7.2% WWE had hirsutism; 15–27% -functional hyperprolactinemia; 21% -increased testosterone; 20% - hipo-progesteronemia. Results of ultrasound examinations showed that ovaryvolume in WWE was normal and significantly less than in group II withPCOS (p£0.05).

Conclusion: The comparative study in these groups revealed that therewere no signs characteristic of diagnosis of PCOS in women with epi-lepsy compared to the women with PCSO. Menstrual cycle disturbanceswere reversible: replacement of VPA with LTG or LEV normalizedendocrine function in women with a previous endocrine disorders.

p470TISSUE DOPPLER EVALUATION OF DIASTOLICFUNCTIONS IN PATIENTS WITH NEWLY DIAGNOSEDAND UNTREATED PATIENTS WITH GENERALIZEDEPILEPSYM. Bilgi, D. Yerdelen, and Y. ColkesenBaskent University Faculty of Medicine, Adana, Turkey

Purpose: Background: Sudden unexpected deaths in patients with epi-lepsy (SUDEP) are common. Epileptic discharges alter vital autonomiccontrol of cardiac functions by affecting central autonomic network.Ratio of early mitral flow velocity (E) to early mitral annulus velocity(e’) (E/e’) is a reliable noninvasive parameter that reflects increased leftventricular diastolic pressure. This measure is correlated with the severityof diastolic dysfunction. Aim: The purpose of the present study is todetermine the diastolic functions of left ventricule by assessing E/e’ ratioin patients with generalized epilepsy.

Method: Thirty consecutive patients with generalized epilepsy and ageand gender matched control group prospectively enrolled. Mean age ofthe epilepsy group was 27€9 and 53% were male. The diagnosis of epi-lepsy was newly established in all patients, and they had not previouslyused any antiepileptic drugs. The duration and frequency of seizure were2 days to 30 years and everyday to twice in 30 years, respectively. Dis-eases and treatments that may affect cardiac and autonomic functionswere exclusion criteria. The subjects were evaluated by tissue Dopplerechocardiography and E/e’ ratio were calculated.

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Result: E/mean e’ ratio was 8.22 € 2.52 in patients with generalized epi-lepsy and 6.74 € 1.10 in control group (p = 0.005).

Conclusion: The significant elevated E/mean e’ value in patients withgeneralized epilepsy compared with control group demonstrates that leftventricular diastolic pressure is affected unfavorably and left ventricularfilling pressure is elevated indirectly in epilepsy group. This finding maybe as a result of autonomic cardiac dysfunction encountered in patientswith epilepsy. Our results suggest that tissue Doppler echocardiographymay be used to anticipate autonomic cardiac dysfunction and SUDEP infuture.

p471BURNS: A LESION UNDERESTIMATED IN INTRACTA-BLE TEMPORAL LOBE EPILEPSYE. Quintero L�pez*, M. P. Mata Mendoza*, M. A. AlonsoVanegas*, H. Sent�es Madrid�, R. M. Buentello Garc�a*, andF. Rubio Donnadieu**Instituto Nacional de Neurolog�a y Neurocirug�a, DistritoFederal, Mexico; and �Instituto Nacional de Nutrici�n yCiencias M�dicas ‘‘Salvador Zubir�n’’, Distrito Federal, Mexico

Purpose: To investigate and describe the incidence, severity and cir-cumstances of burns during seizures in females with medical intractabletemporal lobe epilepsy (TLE).

Method: We retrospectively review a series of 100 female patients withintractable pharmacoresistant TLE secondary to mesial temporal sclero-sis (MTS) operated at the National Institute of Neurology and Neurosur-gery from July 2008 to December 2011. We analyze genre, type andfrequency of seizures, socioeconomic status, and nature, severity and cir-cumstances of any burns suffered secondary to seizures.

Result: Complex partial seizures (CPS) were present in all patients;mean seizure frequency was 12 (6–30) per month. Thirty-seven (37%)patients showed and recalled having had burns during a seizure and allthese cases belonged to very low socioeconomic status. Main type ofburns: scalds from hot fluids, burns during cooking or ironing. Areas ofthe body most commonly affected were the face, anterior neck, hands andtrunk, with major burns in 30%, moderate burns in 40% and minor burnsin rest 30%.

Conclusion: People with intractable epilepsy have a higher risk of acci-dental burns than those without seizures. It seems that these lesions areunderestimated and a specific question regarding this topic should beapproach directly. Socioeconomic status and activity appears to be extre-mely relevant factors for this condition.

p472WOMEN WITH EPILEPSY IN PERIMENOPAUSE ANDMENOPAUSEG. Luef, A. Kullick, M. Prieschl, M. Bergmann, G. Walser,I. Unterberger, C. Brezinka, and L. WildMedical University Innsbruck, Innsbruck, Austria

Purpose: The age at which women experience menopause may be influ-enced by epilepsy. Perimenopause is associated with a decline in serumestradiol and progesterone levels, the perimenopausal development ofanovulation is associated with an increase in estradiol to progesteroneratios that can increase neuronal excitability and exacerbate seizures. Theaim of our study is to identify if menopause, ‡1 year after last menses,benefit seizures and would a decrease occur only in women who had acatamenial pattern of seizure exacerbation previously?

Method: A standardized questionnaire was applied to evaluate changesof seizures associated to menstrual cycles in 100 consecutive women

with epilepsy, aged ‡ 45 years, seen at the University Hospital Innsbruck,during a one year period. Additionally we investigate laboratory changesof estradiol and progesterone.

Result: Seventy two women had a mean age at last menses of 49.2 years(SD € 4.1, range 38 to 57 years). No confounding influences such as his-tory of cigarette smoking, number of pregnancies, or use of enzyme-inducing antiepileptic drugs were present. Sixty eight percent of thewomen reported either that their epilepsy changed or first began duringmenopause. 53% noted an improvement ‡1 year after last menses 20%,reported worsening of their seizures with menopause, and 27% describedno changes. An elevation of the estrogen to progesterone ratio could bedemonstrated in the Perimenopause.

Conclusion: Marked hormonal changes in the menopausal transitionseem to have an effect on seizure susceptibility.

p473A DECISION SUPPORT MODEL OF PRECONCEPTIONCOUNSELLING FOR WOMEN WITH EPILEPSYJ. Winterbottom*, A. Jacoby�, and G. Baker�

*The Walton Centre NHS Foundation Trust, Liverpool, UK; and�The University of Liverpool, Liverpool, UK

Purpose: Women with epilepsy (WWE) are at increased risks of adversepregnancy outcomes, yet little research has addressed their perceptionsof pregnancy-related risks or how they make reproductive health deci-sions when preparing for pregnancy. Preconception counselling offers anopportunity to prevent and/or reduce risks through health promotioninterventions. We undertook a qualitative study to explore professionaland patient factors influencing the outcomes of preconception counsel-ling interventions.

Method: 85 WWE (mean age 27.8 years) participated in this study, ofwhom; 61 women took part in a focus group, and 24 women wereobserved during preconception clinic attendance and later interviewedabout decisional outcomes. We explored how women perceived riskinformation and made judgements concerning pregnancy planning.

Result: Four major themes were identified, with some variation betweenthe stages of pregnancy contemplation: (1) differences between lay andprofessional definitions of planned pregnancy influence decisions tocommence preconception interventions; (2) risks are perceived as fright-ening and fearful – focusing on the health of the unborn child; (3) not allwomen perceive the risks and benefits of preconception interventions inthe same way, and (4) women felt uneasy making decisions – seen ascomplex and challenging, and spread over time.

Conclusion: The results highlight the individual variability betweenwomen's reproductive decisions, influenced by the social contexts oftheir plans for pregnancy. The importance of recognising personal beliefsregarding pregnancy and seizure-related risks are essential to understand-ing poor treatment adherence during pregnancy. These findings haveimportant implications for service development and promoting theuptake of preconception care for WWE.


p474LONG TERM PROGNOSIS OF CHILDREN WITH EPI-LEPSY IN RURAL INDIAD. K. Pal*, S. Sengupta�, G. Chaudhury�, and T. Das�

*King's College London, London, UK; and �SANCHAR-AROD,Kolkata, India

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Purpose: The long-term medical and social prognosis of children withepilepsy in developing countries is almost entirely unknown. We con-ducted a ten year follow-up of 94 children recruited to a randomized con-trolled trial of antiepileptic drugs (AEDs) in 1996 in 40 villages of ruralIndia.

Method: Community disability workers returned to the participants’houses and tracked down participants and relatives. To collect follow-updata we used a standardized health questionnaire for medical outcomes,the Social Integration Scale (SIS) for social outcomes, and verbal autopsymethods for deceased individuals. We also administered the SIS to 122age/sex matched peers for comparison.

Result: We traced vital information on 77 of the original cohort (82%).Seven of the 77 were reported deceased with causes including drowning(n=3), accidental (n=1) and unknown (n=3). 40 surviving participants(57%) reported at least one year seizure remission, 17 (24%) had neverbeen seizure-free. Only 11 individuals remained on AEDs. Men with his-tory of childhood epilepsy had significantly less social activity but simi-lar educational and economic opportunities as peers. Women withhistory of childhood epilepsy were less likely to finish school or take partin social activities, but had the same frequency of marriage and childrenas peers.

Conclusion: Childhood onset epilepsy is associated with a significantmortality in rural India. Survivors have similar rates of long-term seizureremission as in developed economies. Social relations and inclusion areimportant targets for community-based intervention because these defi-cits persist from childhood. However, longer term family (for women)and economic (for men) outcomes are favourable.

p475TOWARDS PREDICTING INDIVIDUAL OUTCOME INPATIENTS AFTER TEMPORAL LOBE SURGERY FORHIPPOCAMPAL SCLEROSIS: WHITE MATTER FDGAND [11C]FLUMAZENIL BINDINGJ. Yankam Njiwa*, S. Bouvard�, N. Costes�, H. Catenoix�,P. Ryvlin§, and A. Hammers**Neurodis Foundation, Lyon, France; �CERMEP-Imagerie duvivant, Lyon, France; �Hpital Neurologique PierreWertheimer, Lyon, France; and §Institute for Child andAdolescent with Epilepsy (IDEE), Hospices Civils de Lyon,Lyon, France

Purpose: One third of patients with hippocampal sclerosis (HS) under-going epilepsy surgery fail to become seizure free (NSF); risk factorsinclude bilateral pathology and frequent generalized seizures. At thegroup level, increased periventricular [11C]flumazenil binding (indicat-ing heterotopic neuron concentration) was associated with NSF outcome(Hammers et al. Epilepsia 2005;46:944–948). Here, we investigate innew larger cohorts whether preoperative white matter (WM) uptake of[11C]flumazenil or the more widely used FDG predicts NSF outcome inindividuals.

Method: Sixteen patients with MRI-defined HS had preoperative FDGand [11C]flumazenil PET, and at least 23 (median 68) months’ follow-up.They were compared with controls (30 FDG, 41 [11C]flumazenil) usingSPM8 with explicit periventricular WM masking. Global radioactivityconcentrations were adjusted via group-specific ANCOVA. Differentcutoffs for distinguishing NSF and seizure free (SF) patients were investi-gated.

Result: Seven patients were NSF (not Engel IA) during follow-up. NSFversus SF patients had periventricular increases predominating contralat-erally on [11C]flumazenil PET (z=2.5–4.4), which were less marked onFDG PET (z=2.8). Against controls, NSF patients showed prominent

[11C]flumazenil increases (zmax=4.8, 6.2cm3), but not SF patients(zmax=3.8, 0.87cm3). For FDG, NSF showed zmax=4.6, 5.4cm3 and SFzmax=4.1, 0.78cm3. For individuals, periventricular increases versuscontrols with zmin=3.5 and pmax=0.5 differentiated best between NSFand SF patients, showing increases in 5/7 NSF patients for both [11C]flu-mazenil and FDG and 1/9 ([11C]flumazenil) and 5/9 (FDG) SF patients(accuracy 81% for [11C]flumazenil, 56% for FDG).

Conclusion: If large numbers of control datasets are available, periven-tricular [11C]flumazenil but not FDG uptake may predict individual post-operative outcome in HS.

p476MORTALITY RISK IN PEOPLE WITH CONVULSIVEEPILEPSY: 8 YEARS’ FOLLOW-UP OF A COHORT INRURAL CHINAD. Ding*, W. Wang�, J. Wu�, Z. Hong�, P. Kwan§, G. Bell–,H. De Boer**, and J. W. Sander–

*Fudan University, Huashan Hospital, Shanghai, China;�Beijing Neurosurgery Institute, Beijing, China; �Institution ofNeurology, Shanghai, China; §Chinese University of HongKong, Hong Kong, China; –UCL Institute of Neurology, London,UK; and **SEIN, Halarm

Purpose: Data on mortality, especially providing standardized mortalityratios (SMRs) or describing the cause of death, are still lacking fromresource-poor settings. In 2008, we conducted a second follow-up surveyin a cohort of people with convulsive epilepsy in eight rural counties inChina. This longitudinal prospective study allowed us to investigate thepattern of cause of death and long-term mortality risk among people withepilepsy over eight years of follow-up.

Method: We tried to trace all subjects who participated in an assessmentof epilepsy management at primary health level during 2000 to 2004.Demographic data, clinical characteristics, survival status and putativecause of death were recorded. The proportional mortality rates (PMRs)for each cause, and SMRs for each age-group and cause were estimatedbased on the 2004 Chinese population. Multivariate analysis of Cox pro-portional hazards regression model was used to detect risk factors associ-ated with increasing mortality.

Result: There were 203 reported deaths among 1983 people with epi-lepsy during a mean follow-up time of 6.1 years. The highest PMRs werefor epilepsy-related death (41.9%) including drowning (14.3%) and sta-tus epilepticus (13.3%). The risk of premature death was 2.9 times greaterin people with epilepsy than in the general population. Much higher risk(SMR: 30.0 to 31.3) was found in young people aged 10–29 years old.Onset before 12 years old, duration of over 10 years, and living in awaterside area were determined as independent predictors for the increas-ing mortality due to epilepsy-related death.

Conclusion: Epilepsy-related death was the leading putative cause ofdeath in rural China. Predictors of increasing mortality suggest interven-tions with efficient treatment and education to prevent premature mortal-ity among people with epilepsy in resource-poor settings.

p477PRIMARY READING EPILEPSY: CASE REPORTH. L. Gul*, O. Karadas�, H. Tutkan�, and Z. E. Ozturk§

*Kartal Education and Research Hospital, Istanbul, Turkey;�Erzincan Military Hospital, Erzincan, Turkey; �OccupationalDiseases Hospital, Istanbul, Turkey; and §Anatolian Hospital,Kastamonu, Turkey

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Purpose: Reading epilepsy is a rare form of reflex epilepsy which wasfirst described in 1956 by Bickford et al. Primary reading epilepsypatients have: absence of pathological signs, seizures only following pro-longed reading, prodromal sensation of the jaw and generally normalresting EEG. We reported a case of primary reading epilepsy patient thatgave response to valproic acid therapy.

Method: A 21 year old male presented partial seizures that alwaysoccurred during both silent and loud reading. Seizures began at the age of19 years. Since then; he had experienced a total of 7 seizures in which 2had become generalized tonic-clonic. He had no family history of epi-lepsy. Physical and neurological examinations, cranial magnetic reso-nance imaging were normal. Detailed EEG and activation studies (sleepdeprivation, silent and loud reading while EEG) were all normal.

Result: Valproic acid treatment 1000mg/day was started. During 6months of follow up after therapy, he was seizure free.

Conclusion: In some patients with primary reading epilepsy, it was notpreferred to use drug treatment, especially if they have no generalizedconvulsions. Reading epilepsy has been reported to respond well to val-proate as in our patient. Some patients may worsen with carbamazepinebut clobazam or clonazepam may also be needed.

p478SILENT STROKES IS A RISK FOR EPILEPSY INELDERLY POPULATIONI. K. AbdulzahraHawler Teaching Hospital, 53, Iraq

Purpose: To show the significance of silent strokes as possible risk fac-tor for epilepsy among middle age and elderly patients having late onsetepilepsy.

Method: This cross-sectional study (survey) was carried out at RizgaryTeaching Hospital, Erbil, Iraq from January to May, 2010. Patients wereincluded in this study if they were middle aged and elderly patients, hav-ing unprovoked acquired first seizure or multiple seizures, previously orrecently diagnosed as epileptic regardless the number of fits which couldbe single or multiple, having history of recent or old stroke or TIA.

100 Iraqi patients were included in this survey. The MRI images wereexamined and interpreted through collaborative discussions between aconsultant Radiologist and a consultant Neurologist.

Data were tabulated and analyzed, the significance of certain parame-ters was measured using chi square test, A p-value of £0.05 was consid-ered statistically significant.

Result: In this studyepilepsy was mostly observed in elderly population(70–79years) and p value was not significant regarding sex differences inthe studied sample. Silent strokes were observed mostly in elderly popu-lation (63–67%). Hypertension, hyperlipidemia, smoking, and oldstrokes are the commonest comorbidities observed in relation to epilepticpatients with silent strokes, and partial secondary generalized epilepsytype was the commonest epilepsy variety observed (73%).

Conclusion: Silent strokes were common in elderly patients having epi-lepsy (53%), and its prevalence increase with age and hypertension.Silent strokes observed in brain MRI can be an indirect way to establishthe causes of epilepsy in elderly population.

p479PRIDICTION OF EFFECTIVENESS OF THE FIRST AN-TIEPILEPTIC DRUG IN THE ELDERLY PATIENTSWITH EPILEPSYS. Lukic, and M. SpasicUniversity Clinical Centre, Nis, Serbia

Purpose: Assessment the values of the initial clinical predictors ofeffectiveness of the first antiepileptic drug in the elderly patients withepilepsy.

Method: Prospective longitudinal study included consecutive series ofelderly with newly diagnosed partial epilepsy. Inclusion criteria were: 1)Subjects older than 65 years, with untreated, newly diagnosed epilepsy 2)Subjects had no previous use of an AED, 3) Electroencephalogram(EEG) compatible with localization-related epilepsy (to exclude primarygeneralized epilepsy), 4) Neuroimaging confirming the absence of a pro-gressive neurological lesion.

Patients were following minimum 12 mounts after initiation of ther-apy. Primary endpoint was seizure control (with or without seizures).Potential predictors are analyses from dataset available on initial clinicalevaluation and included demographic data, history risk factors, neurol-ogy findings, neuroradiology and EEG findings as well as characteristicsof pharmacotherapy.

Univariate logistic regression equations were computed for eachpotential predictor variable. Variables were included in the multivariateanalysis if the univariate p value was < 0.25. A backward selection proce-dure was then used to select subset variables. Statistical significance wasdefined for alpha = 0.05.

Result: 45 elderly patients were included in this study. 25 remain seizurefree after 12 mounts of follow up. Regression analyses demonstrated thatetiology particularly depression traumatic brain injury and depression arethe most important predictor variables for bad therapeutically response.

Conclusion: This study may support hypothesis that neurobiologicalprocesses that underpin psychiatric comorbidity may interact withthose producing seizures to increase the extent of brain dysfunctionand thereby the likelihood of developing bad therapeutic response inelderly.

p480COMPARISON OF SEIZURE DISTRIBUTION AND EEGRECORDINGS OF EPILEPSY PATIENTSI. Ipekdal*, O. Karadas�, H. L. Gul�, Z. Gokcil§, and Z. Odabasi§

*Marasal Cakmak Hospital, Erzurum, Turkey; �ErzincanMilitary Hospital, Erzincan, Turkey; �Kartal Education andResearch Hospital, Istanbul, Turkey; and §Gulhane MilitaryMedical Academy, Ankara, Turkey

Purpose: Epileptic seizures may occur during the daytime, at night orboth in the daytime and at night. The aim of our study is to investigate therelationship between the distribution of seizures in the day with interictalEEG properties.

Method: 48 patients that had generalised or secondary generalised sei-zures were included to the study. 36 patients had seizures that occur dur-ing daytime and 12 patients had seizures that occur during night. Patientsinterictal EEG properties and distribution of seizures in the daytime wereevaluated retrospectively.

Result: In interictal EEG recordings of 36 patients that had seizureswhich occur during daytime: 3 of them showed no abnormalities, 12showed focal, 21 showed generalised abnormalities. No correlationwas detected between these EEG findings and seizure distribution inthe daytime. On the other hand, in interictal EEG recordings of 12patients that had seizures which occur at night: 8 of them showedno abnormalities,3 showed focal, 1 showed generalised abnormali-ties.

Conclusion: These findings suggest that; seizures occuring in the day-time and at night while sleeping may have different mechanisms. Studiesthat searches for epilepsy-melatonin relationship (like sleep-melatoninrelationship) must be made to better understand the etiopathogenesis ofnocturnal seizures.

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p481COEXISTING SEIZURES IN PATIENTS WITH INFAN-TILE SPASMS CONFIRMED BY LONG-TERM VIDEO-ELECTROENCEPHALOGRAPHY MONITORINGH. Kim*, J. H. Lee�, H. W. Ryu�, J. S. Kim*, B. C. Lim�,H. Hwang*, J. H. Chae�, K. J. Kim�, and Y. S. Hwang�

*Sepul National University Bundang Hospital, Seongnam-si,Korea; and �Seoul National University Children's Hospital,Seoul, Korea

Purpose: We performed this study to evaluate the frequency, types, andictal electroencephalography (EEG) findings of coexisting seizures inpatients with infantile spasms at the onset of spasms. We also evaluatedthe effect of coexisting seizures on short-term seizure control.

Method: We retrospectively reviewed the long-term video-EEG andelectronic medical records of 109 patients (58 boys and 51 girls) diag-nosed with infantile spasms at the Seoul National University Chil-dren's Hospital. Coexisting seizure types were classified according tothe International League Against Epilepsy seizure and epilepsy classi-fication. Ictal EEG findings were also reviewed. Short-term seizurecontrol rates were compared between groups with or without coexis-ting seizures.

Result: We identified 27 coexisting seizures in 24 of the 109 patients(22%). The most common type of seizure was generalized tonic seizurefollowed by myoclonic, focal tonic, tonic-clonic, hypokinetic, and ver-sive seizures. Rates of preterm birth and birth asphyxia were significantlyhigher in patients with coexisting seizures. There was no significant dif-ference in short-term seizure freedom (overall seizure-free rates inpatients without coexisting seizures vs. those with: 29.2% vs. 11.1% at 2months, 36.1% vs. 22.2% at 4 months, and 41.7% vs. 27.8% at 6 months).Seizure freedom was significantly lower in the symptomatic groups com-pared with non-symptomatic groups.

Conclusion: Long-term video-EEG monitoring is required as an initialevaluation in patients with infantile spasms, especially when there arereports of coexisting seizures, or a history of preterm birth or birthasphyxia. Presence of coexisting seizures was not related to poor seizurecontrol in the short-term treatment period.

p482SURVEY ON THE MANAGEMENT OF EPILEPSY BYGERIATRICIANSS. L. Jones, and V. AdhiyamanWrexham Maelor Hospital, Wrexham, UK

Purpose: Epilepsy is commonly encountered by geriatricians in clinicalpractice. However approaches to its management vary considerably. Thissurvey aims to quantify this variability.

Method: Members of the Welsh BGS were invited to participate in anonline survey via a weblink. Questions covered referral patterns to spe-cialist services, timing of anticonvulsant initiation, drug choice and useof neuroimaging and EEGs.

Result: 37 responses were received: 21 from Consultants, 12 from SpRsand 4 from Associate specialists. 29.7% would initiate treatment after afirst seizure. 64.9% would defer treatment until second.

Table 1. (First line anticonvulsant choice for each epilepsy type (%))Partial seizures Partial seizures with secondary generalisation Primarygeneralised seizures Sodium Valproate 40.5 54.1 62.2 Levetiracetam32.4 32.4 24.3 Lamotrigine 21.6 18.9 18.9 Driving was the major deter-minant for referral to specialist epilepsy services: 56.8% of respondentsrarely used EEGs. Reasons cited were inaccessibility of local servicesand low yield. 86.5% would request neuroimaging after first seizure.

Conclusion: Significant variability in how geriatricians manage epi-lepsy was demonstrated. This may reflect the weak evidence base andthus poverty of specific guidelines for managing geriatric epilepsy.Extending this regional survey should increase its generalisability andprovide an impetus for a more unified approach to its management infuture.

p483INCIDENCE OF FIRST ACUTE SYMPTOMATIC SEI-ZURES AND UNPROVOKED SEIZURES IN ADULT: APROSPECTIVE, EPIDEMIOLOGICAL STUDY BASEDIN CAPTIVE POPULATION IN ARGENTINAL. Romano, L. Sousa, G. Castellino, J. Zorrilla, F. Latini,P. Alvarez, M. Sanchez, A. Aleman, P. Loli, and S. GonorazkyHospital Privado De Comunidad, Mar Del Plata, Argentina

Purpose: Seizure can be classified as acute symptomatic seizures (ASS)or unprovoked seizures (US), and this distinction is of clinical relevancein relation to treatment and prognosis. This importance, led us to conducta prospective population-based incidence of first ASS and US in adult.Objectives: To determine the crude annual incidence rate, the specificrates according to age and sex based on the Official Argentinian NationalCensus (OANC) of 2001 of the first episode of of ASS and US in adults.

Method: From April 1, 2007 to March 30, 2009, we conducted a pro-spective epidemiologic study to identify patients with first episode ofASS and US in adults >65 years, in the state of Mar del Plata, Argentina.

Result: The crude annual incidence rate of ASS in adults >65 years was30.6 per 100.000 (95% CI: 22.2–44.5), 47.9 per 100.000 (95% CI: 26.2–80.5) in men and 22 per 100.000 (95% CI: 11.7–37.7) in women. In adults>65 the annual US incidence was 87.3 per 100.000 (95% CI: 68.9–109.1), 89.1 per 100.000 (95% CI: 58.2–130.6) in men and 86.4 per100.000 (95% CI: 64.3–113.6) women. A statistically significantincrease (p<0.0001) was observed when comparing rates among differentage groups (65–74 years, 75–84 years and >85 years) for the ASS to theUS. The adjusted annual rate to OANC was 22 ASS per 100.000 and 67.7US per 100.000.

Conclusion: The data presented show one of the few epidemiologicalprospective studies conducted in Argentina and Latin America, showingincidence rates similar to those observed in previous studies in developedcountries.


p484STATE OF BLOOD-BRAIN BARRIER AND NITRICOXIDE METABOLISM IN PATIENTS WITH POST-TRAUMATIC EPILEPSY EARLY AFTER GENERAL-IZED SEIZUREO. Kukhlenko, and R. KukhlenkoLviv National medical University, Lviv, Ukraine

Purpose: Neuron-specific enolase (NSE) is an enzyme detected inserum following structural damage of neuronal brain cells and increasedpermeability of blood brain barrier (BBB). Peroxynitrite anion (ONOO-)– toxic metabolite of nitric oxide, is recognized to play important role inneuronal damaging and development of BBB dysfunction. The aim ofour study was to evaluate the state of blood brain barrier and nitric oxidesystem in patients with posttraumatic epilepsy early after seizureoccurrence.

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Method: We examined 23 patients (14 males and 9 females) with post-traumatic epilepsy early (up to 24 hours) after generalized seizure and 14patients with posttraumatic epilepsy (4 females and 10 males) and rareseizures more than 1 month after last seizure. All the patients survivedmild or moderate traumatic brain injury and took carbamazepine as an-tiepileptic monotherapy. Concentration of NSE, ONOO- and activity ofinducible nitric oxide synthase were estimated in blood plasma.

Result: Received data revealed increase in plasma NSE concentrationearly after seizure 18.8€1.3 ng/ml while compared with control group(17.5€1.1 ng/ml, p

Conclusion: There is an evidence of increased BBB permeability earlyafter generalized tonic-clonic seizure in patients with post-traumatic epi-lepsy. BBB dysfunction is accompanied by increased serum levels of per-oxynitrite and iNOS activity.

p485ANALYSIS OF A GROUP OF PATIENTS WITH POST-STROKE ACUTE AND REMOTE EPILEPTIC SEIZURESI. Chmielewska, A. B. Martinez Garcia, A. Moreno Rojas,M. Massot Cladera, M. C. De La Bandera Sanchez, S. TurCampos, I. Barcelo Artigues, M. Mestre Sanso, and F. J. MolinaMartinezHospital Universitario Son Espases, Palma De Mallorca, Spain

Purpose: Stroke is a frequent cause of epileptic seizures in adults, how-ever, there is limited information based in evidence. Our purpose is toanalyse a group of patients with post-stroke acute and remote epilepticseizures, and use our conclusions to design a future longer prospectivestudy.

Method: This is a retrospective study in which we included haemor-rhagic and ischemic stroke patients with epileptic seizures recorded inour stroke database. Epidemiological data, stroke aetiology, seizuresubtype and time from stroke to the first epileptic seizure were regis-tered.

Result: From January 2009 to December 2010 a total of 378 patientswas studied. 72.2% were men, mean age of 65.39 €13.65 years. Haemor-rhagic and ischemic stroke was diagnosed in 12% and 88% of the patientsrespectively. 3.9% of the patients suffered seizures during the first yearafter stroke, of which 67% had an ischemic stroke (40% cardioembolic,20% due to large artery atherosclerosis, and 40% cryptogenic). Acute sei-zures (< 2 weeks after stroke) were detected in 1.5% of the patients, 67%with haemorrhagic stroke, without recurrences during the first post-stroke year.2.4% of the patients developed epilepsy (considering a firstremote seizure). Partial motor simple seizure was the most frequent type.Antiepileptic treatment was initiated in 93.3% of the patients and wasmaintained during the follow-up.

Conclusion: Although our sample is reduced, the results are in accor-dance with other published series. It has permitted us to analyse our clini-cal management and to design a larger prospective study necessary forour community.

p486UNUSUALLY HIGH INCIDENCE OF INTRACRANIALARACHNOID CYSTS AMONG PATIENTS WITH EPI-LEPSY UNRELATED TO SEIZURE ETIOLOGYD. J. Milivojevic*, and A. Z. Ilic�

*Medical Centre Petrovac, Petrovac, Serbia; and �HealthCenter Studenica, Kraljevo, Serbia

Purpose: This retrospective study was conducted to assess an incidenceof intracranial arachnoid cysts in patients with focal epilepsy and to

establish possible relationship between location of arachnoid cysts andseizure foci.

Method: Our study group comprised 130 patients, aged 15–60 years,affected by simple partial and complex partial epilepsy with or withoutsecondary generalization. They were diagnosed with epilepsy during2010. and 2011. in our neurology department All patients had brain CTsand/or MRI scans and at least two interictal EEGs performed. The exactlocation of seizure focus was defined by history, semiology and EEGfindings.

Result: 9 patients of 130 with focal epilepsy also had large arachnoidcysts found on CT/MRI scans. The most common location of cystswas the middle fossa near the temporal lobe (5 patients), threepatients had frontal lobe cysts and one patient had cyst located retro-cerebellary paramedially. Only one patient with a left temporal lobecyst had sezure focus and semiology related to the location of thecyst. Furthermore, one more patient with a temporal lobe cyst had a‘mirror EEG focus’’ in the exact contralateral region of the brain.Consequently, seizure focus was related to the location of the cyst inonly two of 9 patients (22%) which is consistent with results of otherinvestigators

Conclusion: Our data suggest that arachnoid cysts are most probably anincidental finding in patients with epilepsy unrelated to seizure focus inmost of the cases but its unusually high incidence (7%) in these patientscould be a possible target of investigation.

p487COMPREHENSIVE INFORMATION IMPARTED TOPATIENTS WITH EPILEPSY AND COMORBIDITY ANDDECREASED PREVALENCE OF ADVERSE TREAT-MENT EFFECTS. THE EDU-COM STUDYS. Beretta*, F. Gerardi�, E. Beghi�, and C. Ferrarese**San Gerardo Hospital, Monza, Italy; and �Istituto di RicercheFarmacologiche Mario Negri, Milano,

Purpose: Epilepsy requires long-term drug treatment and is frequentlyassociated with other clinical conditions and multiple drug-therapy inthe elderly. The aim of this study is to provide evidence that a stan-dardized educational strategy may positively affect adverse drug reac-tions, drug interactions and the quality of life in this epilepsypopulation.

Method: The EDU-COM study is a multicenter, randomized, con-trolled, single-blind, pragmatic trial. Recruitment phase terminated inDecember 2011 after 180 consecutive adult epilepsy outpatients withchronic comorbidities and multiple-drug therapy have been recruitedfrom 8 epilepsy centers nationwide and randomized to receive a compre-hensive and standardized educational plan or usual care. All patients havebeen seen at baselines, at one month and at six months after admission.The primary outcome is the number of patients free from clinically rele-vant adverse treatment events or drug interactions at end of study. Sec-ondary outcomes include health-related quality of life score changesusing the QOLIE-31 questionnaire and the monetary medical costs,including the one-hour meetings with patients assigned to the experimen-tal arm.

Result: Interim analysis showed a significant effect of the standardizededucational plan for the combined primary end-point at the end of fol-low-up (OR = 1.34). This effect appeared to be larger for patients withmore severe side effects/drug interactions at baseline (OR = 1.66). Thefinal results of the study will be presented.

Conclusion: The EDU-COM study will provide novel and evidence-based data on the impact of educational strategies in the clinical manage-ment of epilepsy patients with comorbidities.

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p488INSOMNIA IN EPILEPSY PATIENTS. CLINICAL ANDPOLYSOMNOGRAPHIC CHARACTERISTICS. A RET-ROSPECTIVE STUDYA. Rodriguez*, and E. Koziorynska�

*New York Sleep Institute, New York, NY, USA; and �SUNYDownstate Medical Center, Brooklyn, NY, USA

Purpose: Patients with epilepsy have multiple sleep problems, includinginsomnia. Mood disorders are a significant co-morbidity in epilepsy.There is a high prevalence of insomnia in patients with mood disorders.The clinical and polysomnographic (PSG) characteristics of epilepsypatients with insomnia have not been described.

Method: Medical records of all adult epilepsy patients seen at SleepDisorders Center were reviewed over 6 months. All subjects presentingwith insomnia were selected. Consecutive non-epileptic insomniapatients were selected as controls.

Result: Seventeen adult patients with epilepsy were included. Amongepilepsy patients, 76.7% were women, mean age was 40.7 years and58.8% had partial seizures. Seventy-six percent of patients had troublesto fall asleep and 68.7% had troubles to stay asleep (there was no statisti-cally significant difference with controls). 52.9% of patients were using asleep medication. Zolpidem was the most commonly used medicationamong patients and controls (64.7% and 76.5%), followed by melatonin(41.2% and 41.2%). Patients with epilepsy had a statistically significanthigher percentage of depression compared to controls (52.9% vs. 17.6%,p=0.028). PSG showed a mean sleep efficiency of 69.0% with a meansleep latency of 48.8 minutes among epilepsy patients. These results didnot differ from controls. Sleep disordered breathing was present in 50.0%of patients and 44.4% of controls.

Conclusion: Epilepsy patients with insomnia have a higher prevalencedepression compared controls. There is a high percentage of use of sleepmedications among these patients. The clinical and PSG characteristicdid not differ when compared with controls.

p4893D-TELEVISION AND THE RISK OF SEIZURES INCHILDRENL. Navarro-Ramirez*, H. Plischke�, J. Riess�, C. Bumel�,C. Von St�lpnagel�, M. Staudt�, and G. Kluger�

*Zentrum f�r Kinder und Jugendliche Inn Salzach, Altçtting,Germany; �Generation Reseach Program, Bad Toelz, Germany;and �Schçn Klinik Vogtareuth, Vogtareuth, Germany

Purpose: In 1997 approximately 685 Japanese children were hospital-ized by suspected epileptic seizures after watching a Pokemon series. In2010 a 42-year-old man in Taiwan died while watching the 3D epic(3DE) Avatar. The risk of seizures while watching 3D in patients withepilepsy has not been systematically examined yet.

Method: After a 20 min Routine-EEG with Photo stimulation (PS) runsa 15 min Video-EEG, meanwhile was the 3DE Ice Age watched. A 50inches 3D- Plasma-TV with 3D-Shutter glasses was used in a 9-m2 roomwith a 2 m watching distance. Each EEG was independently from 2 phy-sicians (LN-R, GK) visual evaluated.

Result: To date 150 patients (77 male, mean age 12) were analyzed. 84patients had epilepsy. 15 patients presented a photo paroxysmal reaction(PPR). 1 patient with epilepsy (4 seizures/day) had a seizure shortly after3D. 3 patients with idiopathic generalized epilepsy had an increase of epi-leptic discharges (ED). In all other patients neither seizure could be pro-voked, nor did the ED increase while viewing 3D-TV. 10 patientspresented a reduction from of ED. 25 patients complained about nausea,

headache and dizziness and in most of the patients lambda wavesappeared during 3D.

Conclusion: In this running study, until now, an increase of ED wasdetected in 3 of 84 children with epilepsy (3.6%) while watching 3D. Thereduction of ED during 3D can be interpreted as an increase of alertness.A seizure during 3D was not observed. The risk to provoke a seizurewhile watching 3D is apparently low and does not seem to be a matter oftechnology (3D or 2D), but rather a matter of the video content (for exam-ple particular colors or repetitive figures). A high percentage of thepatients however reported vegative symptoms like in motion sicknessduring 3D.

p490SCREENING OF SLEEP DISORDERS IN THE EPILEPSYPATIENTSM. E. Contreras Pinto, T. Rodriguez Riquelme, R. Julliet Perez,J. A. Gonzalez Hein, and R. Galeno TrewelasHospital DIPRECA, Santiago, Chile

Purpose: The reciprocal influence between epilepsy and sleep disorderscan worsen the prognosis for both processes. Was raised as a main objec-tive of the present study, to screen the sleep disorders (SD) in patientswith epilepsy and so be able to design an intervention plan.

Method: Were surveyed 37 patients and 41 controls, with similar char-acteristics in gender and age. The questionnaire included, among othervariables, Epworth sleepiness scale and SA-SDQ for sleep apnea.

Result: 34% of epileptic patients has some sleep disorders (29% in con-trols, p<0.05). The most frequent one was symptoms of insomnia (40%),followed by the bruxism and restless legs syndrome. A 29% of patientshave SA-SDQ altered suggestive of sleep apnea. A 13% recognized timeof night-time sleep insufficient and 16% excessive daytime sleepiness.Epileptic patients with good control of crisis were correlated with bettersleep hygiene (52% vs 25%), lowest sense of daytime sleepiness (36%vs75%) and lower BMI (26vs30) compared with patients with worst con-trol of crisis.

Conclusion: The frequency of sleep disorders is high, even higher thanthe control population, especially insomnia and probably sleep apnea.Data that allow us to increase the index of suspicion and intervene inthese patients.

p491SEIZURES AND ALCOHOLS. Grabova, S. Mijo, I. Zekja, and J. KrujaUHC Mother Theresa, Tirana, Albania

Purpose: The association of seizures and alcohol abuse is well estab-lished (Lennox, 1941). Seizures, epilepsy and alcohol use are complexlyinterrelated, and research in this field suffers from a lack of unanimity interminology and definitions. We all know that seizure constitutes one ofthe most frequent and challenging medical complication of alcoholabuse.

Method: We studied the patients presented with acute seizures in neu-rology emergency room of University Service Center Mother Theresa ofTirana, during the last year.

Result: We identified 62 patients with acute seizures (37 males and 25females). 40 patients had SE (30 of them [75%] were previously diag-nosed with epilepsy). 10 patients (16.1%) had seizures related to alcoholuse (4 patients) or withdrawal (6 patients). All of them were males agedfrom 30–48 years old (mean age 34.4 years old). A detailed analysis ofalcoholic seizures is done. A review of the literature on alcohol effects onseizures is presented too.

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Conclusion: The association of seizures and alcohol abuse is well estab-lished (Lennox, 1941). Seizures, epilepsy and alcohol use are complexlyinterrelated, and research in this field suffers from a lack of unanimity interminology and definitions. We all know that seizure constitutes one ofthe most frequent and challenging medical complication of alcoholabuse.

p492ARE BENZODIAZEPINES PROTECTIVE AGAINSTPROPXYPHENE ABUSE ASSOCIATED SEIZURESS. Kaushal, M. Jain, S. Arora, and G. SinghDayanand Medical College and Hospital, Ludhiana, India

Purpose: To determine the pattern of substance abuse associated withseizures

Method: The study was conducted over a period of 15 months inpatients attending epilepsy clinic at the Institution. Patients with historyof substance abuse, consenting to participate in the study, were evaluatedto determine the details of substances abused, resultant seizures, temporalrelationship of seizures with substance abuse and drug therapy. In addi-tion the patient demographics were recorded.

Result: Among 42 patients fulfilling the criterion and consenting to par-ticipate in the study, 64% were in the age group of 16–35 years. All thesubjects were males (100%). Most of them had history of multiple sub-stance abuse. Among the single substances abused, alcohol was the com-monest (72%). Among Opiates, Propoxyphene (47%) was mostcommonly abused. Generalized Tonic Clonic (GTC) Seizures was thecommonest presentation followed by a combination of GTC and Myo-clonic seizures (seen specifically in propoxyphene abusers). The seizureswere observed during withdrawl with abuse of alcohol and benzodiaze-pines while seizures were during intoxication phase with opiates. Con-comittant use of benzodiazepine and propoxyphene was protectiveagainst withdrawl seizures observed with propoxyphene.

Conclusion: Alcohol was the commonest substance abused resulting inseizures. GTC seizures was the commonest semiology. Among opiates,propoxyphene was the commonest substance abused. The charactersticsemiology in these patients was myoclonic jerks preceeding GTC sei-zures. Concomittant Benzodiazepine use with propoxyphene was protec-tive in these patients. Benzodiazepines can be used as a treatment optionin patients presenting with propoxyphene abuse associated seizures

p493DOES ATMOSPHERIC PRESSURE CORRELATESWITH SEIZURE FREQUENCY IN EPILEPSY MONI-TORING UNIT AND EMERGENCY DEPARTMENT?A. J. Ristic*, D. Jovanovic�, G. Trajkovic�, S. M. Jankovic*,N. M. Vojvodic*, M. M. Kovacevic*, V. L. Bascarevic§, andD. V. Sokic**Neurology Clinic, Belgrade, Serbia; �Regional Hospital‘‘Zemun’’, Belgrade, Serbia; �Medical School BelgradeUniversity, Belgrade, Serbia; and §Clinic of Neurosurgery,Clinical Center of Serbia, School of Medicine, University ofBelgrade, Belgrade, Serbia

Purpose: To investigate correlation of the seizure frequency in patientsundergoing long-term video EEG monitoring and patients presented inemergency department (ED) with atmospheric pressure (AP) changes.

Method: Historical automated AP data (January 2008–November 2011)from weather station in the Belgrade area (100m aside of hospital facili-ties) were correlated to seizure frequency in: 1) consecutive patientsundergoing long-term video EEG monitoring at our institution and 2)

consecutive patients presented in emergency department. AP, daily maxi-mum, minimum and range between maximum and minimum of AP werecorrelated to daily number of seizures per patient.

Result: In the period of interest a total of 1721 epileptic seizures (23%generalized tonic-clonic seizures - GTCS) occurred in 265 patients invideo-EEG monitoring unit. In the same period 5053 patients presentedto the ED due to 5120 epileptic seizures (45% GTCS). We found weaknegative correlation between number of seizures per patient and valuesof AP in video-EEG monitoring unit (Spearman rank coefficient -0.07;p<0.01). We also found a bit stronger negative correlation between num-ber of seizures per patients and values of AP in patients presented in ED(Spearman rank coefficient -0.11; p<0.01). Very similar and statisticallysignificant results were demonstrated with following variables: dailymean AP, maximum or minimum, and range between maximum andminimum of AP change in both clinical settings.

Conclusion: We found mild evidence to suggest lower atmosphericpressure made seizure occurrence more likely in video-EEG monitoringunit and more general population of patients presenting at ED.


p494FACTORS INFLUENCING QUALITY OF LIFE IN 160SUBJECTS WITH EPILEPSY AND THEIR CAREGIVERSA. Alam, M. M. Mehndiratta, S. Pandey, and R. NayakG.B Pant Hospital, New Delhi, India

Purpose: To assess the quality of life (QOL) of People with Epilepsy(PWE) and their caregivers using the QOLIE-31and SF36 Instrumentsand to study the predictors of QOL.

Method: This study was conducted at G. B. Pant Hospital using a crosssectional design. Total 160 subjects with epilepsy (all types) of at leastone year duration and their care givers of age range 18 to 60 years wereincluded. Detailed history and demographic characteristics wererecorded in a structured proforma. Assessment was done by usingadapted version of QOLIE 31 (Quality of Life in Epilepsy Subjects 31)for epilepsy subjects and SF 36 (Short Form Health Survey 36 version 2)for their care givers

Result: There was male preponderance and subjects (78.75%) wereyoung (age<30 yrs). Generalized seizure (65.63%) was the most commontype of seizure and majority of subjects (74.37%) had epilepsy of lessthan 10 year duration. Low education and socioeconomic status, earlierage of onset, higher frequency of seizures, more duration of epilepsy andless time passed since last episode of seizure and polytherapy were pre-dictors of lower quality of life in subjects and care givers. QOL was foundto be low if care giver was female (mother or wife of subject).

Conclusion: Patients with epilepsy as well as their caregivers have poorquality of life which may be related to disease per se, drug therapy and avariety of social factors. Their proper assessment and relevant manage-ment should be included in the holistic epilepsy care.

p495EMPLOYMENT OF PEOPLE WITH EPILEPSY FROMTHE PERSPECTIVE OF PATIENTS, NEUROLOGISTSAND THE GENERAL POPULATIONB. Majkowska-Zwolinska*, and J. Jedrzejczak�

*Foundation of Epileptology, Warsaw, Poland; and �MedicalCentre for Postgraduate Education, Warsaw, Poland

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Purpose: To present the profile of employed epileptic patients (EP) inPoland and opinions of patients, neurologists and the Polish populationabout employment of persons with epilepsy.

Method: A questionnaire-based study was carried out in 2009 all overPoland and included: EP 18–65 yrs (995), neurologists (179) and a rep-resentative sample of Poles (1042). Computer-assisted personal inter-views and paper-and-pencil questionnaires were used. TheInternational Standard Classification of Occupations (ISCO) was usedto classify jobs.

Result: Out of 995 EP, 49% were employed and 51% did not work at thetime of the survey; 67% of them had full time jobs. There were no genderdifferences. Most of the patients worked in the following occupationalgroups (according to ISCO): professionals (23.0%) clerical supportworkers (21.8%), technicians and associate professionals (20.4%). Per-sons with higher education and with good control of seizures (£ 1 seizure/year) had a better chance of employment, OR=2.92; 95% CI 2.20–3.88and OR= 1.85; 95% CI 1.34–2.56 respectively. 25% of EP, 28% of neu-rologists and 56% of Poles expressed the opinion that every EP can work,and 63%, 72% and 29%, respectively expressed the opinion that they canwork with some limitations. In the opinion of 11% of EP and 8% of Poles,EP should not work at all.

Conclusion: Persons with epilepsy with good control of seizures andbetter education have a better chance of employment. Choice of occupa-tion reflects patients’ medical limitations. Poles have a generally positiveattitude toward the employment of persons with epilepsy.

p496EPILEPSY-ASSOCIATED STIGMA IN BOLIVIA: ACOMMUNITY BASED STUDY AMONG GUARAN� POP-ULATION. A ILAE/IBE/WHO GLOBAL CAMPAIGNAGAINST EPILEPSY REGIONAL PROJECTE. Bruno*, A. Bartoloni�, V. Sofia*, F. Rafael3,4, D. Magnelli�,S. Padilla–, G. Quattrocchi*, F. Bartalesi�, H. Segundo**,M. Zappia*, P. Preux3,4, and A. Nicoletti**University of Catania, Catania, Italy; �Careggi Hospital,Firenze, Italy; �School of Medicine, Institute of TropicalNeurology, Univ. Limoges, Limoges, France; §CHU Limoges,Limoges, France; –Teko Guaran�, Camiri, Bolivia; and **SantaCruz, Camiri, Bolivia

Purpose: Epilepsy is associated with a significant burden of stigmaespecially among traditional society. Stigma has been shown to have anegative effect on management of people with epilepsy (PWE) represent-ing one of the major factors that contribute to the burden of epilepsy. Thecurrent study was designed to assess stigma perception among Guaran�population in order to identify the main determinants of the stigmatiza-tion process on which it should be act in the attempt to overcome stigmarelated to epilepsy and its consequences.

Method: A group of PWE, a group of relatives of PWE, a group ofhealth-care personnel and a group of students living in Guaran� commu-nities in Bolivia were invited to complete the Stigma Scale of Epilepsy(SSE) questionnaire.

Result: One hundred thirty-two people completed the questionnaireshowing a moderate perception of stigma among these communities. Themain determinants of stigma identified in this population were: the fearlinked to loss of control, the feelings of sadness and pity toward PWE andthe difficulties faced by PWE in the professional and relationship fields.Others predictors of stigma were level of education and type of seizurefor PWE.

Conclusion: Our study pointed out that, among Guaran�, PWE face dif-ficulties in everyday life because of epilepsy related stigma and attestedhow cultural aspects and lack of knowledge contribute to perpetuate

stigma in this society. From this rises the importance to promote commu-nity-based educational programs aimed at reducing the stigmatizationprocess that may represents one of the major obstacles to the managementof epilepsy.

p497IMPACT OF STIGMA ON QUALITY OF LIFE OFPATIENTS WITH REFRACTORY EPILEPSYE. I. Viteva-VelkovaMedical University - Plovdiv, Plovdiv, Bulgaria

Purpose: To assess impact of stigma on life quality of Bulgarianpatients with refractory epilepsy.

Method: We studied 70 patients with refractory epilepsy who were 18–65 years of age, without cognitive decline, progressive somatic or neuro-logical disease or recent seizures. All participants fulfilled QOLIE-89and a 3-item stigma scale with an additional question about the patient'sopinion on the reason for the unusual attitude of people.

Result: The patients were with a mean disease duration 25.07€1.32years. 17 (24.29%€5.13) of them had partial seizures, 16 (22.86%€5.03)– generalized seizures and 37 (52.86€5.97) – polymorphic ones. Mostoften they had high weekly (45.71%) or monthly (30%) seizure fre-quency despite the prescribed polytherapy in 90% of cases. The greatestpercentage of them (40%€5.86) had symptomatic epilepsy.

We found out stigmatization in 44% of participants, 29% wereseverely stigmatized. The most frequently defined reason (by 58.54%)was people's fear of seizures because of inability to act adequately. Stig-matization had a negative impact on the total value of QOLIE-89 (47.80as a T-value) as well as all subscales of QOLIE-89 (P<0.01) with theexception of ‘‘Change in health’’ and ‘‘Sexual relations’’ P>0.05. Thehighest percentage of stigmatized patients who made very low and lowassessments was for the subscales ‘‘Health perceptions’’ (82.9%), ‘‘Emo-tional well-being’’ (71.5%), ‘‘Memory’’ (63.4%) and ‘‘Health discour-agement’’ (62.5%). All assessments were negatively correlated withstigmatization severity.

Conclusion: All aspects of life quality of Bulgarian patients withrefractory epilepsy correlate negatively with the level of their stigma-tization.

p498EXPERIENCE OF EPILEPSY IN A SENEGALESE SER-IES OF PATIENTSL. B. Seck, K. Toure, M. Ndiaye, L. Gueye, A. G. Diop, andM. M. NdiayeFann Teaching Hospital, Dakar Fann, Senegal

Purpose: To assess epilepsy impact on daily life of patients sufferingfrom it.

Method: Prospective study on patients suffering from epilepsy the neu-rological department of Fann teaching hospital in Dakar.

Result: One hundred and twenty three patients have been questionned.Mean age was 22.5 years, with 55.3% males and 44.70% females. Sev-enty one point five per cent think that epilepsy is an organic disease,6.5% link it to evel phenomenon, while 22% don't know how to qualifyit. Sixty four point two per cent of patients perfectly comply with thetreatment, 29.3% do not regularly take it, 6.5% have interrupted it. Forthe 74% of patients that answered to this question, therapy is not consid-ered as restricting. Eighty four point five per cent of patients maintain tohave been improved by the therapy. The main side effects of treatmentwere neurological and genital. Only 57.32% of school age patients wereprovided with schooling, with decreasing of school efficiency under ther-apy in 40.42%. Bearing of the treatment costs is provided by parents for

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63.4% of patients, the patients themselves for 33.3%, by friends or socialassistance for 3.3%. Forty two point twenty seven per cent appeal to tradi-tional practitioner, with failure in 86.53% of cases. For 53.55% ofpatients, close contacts are informed of the disease, and reactions arerather pejorative in 54.54% of cases.

Conclusion: Epilepsy still keeps pejorative connotation in african socie-ties. Side effects of therapy add up to the impact of the disease on dailylife, facilitating impairment of quality of life.

p499A SURVEY OF MEDICAL ASSOCIATION MEMBERS INTHE SAN-IN REGION ON THE MEDICAL TREATMENTOF PEOPLE WITH EPILEPSYS. Yoshioka, S. Takama, and M. SaigaTottori University, Yonago, Japan

Purpose: To carry out the medical cooperation necessary for peoplewith epilepsy (PWE), it is important to clarify the number of PWE andthe actual condition of treatment for PWE. Therefore, we investigated themedical situation of PWE by administering questionnaires to all themembers of the medical association in the San-in region.

Method: A questionnaire asking about clinical department, workplace,number of patients with epilepsy, medical society and information sourceon epilepsy medical care and welfare was distributed to both the Tottoriand Shimane medical association members in 2010, and a total of 886(35.1%) responses were collected.

Result: Of the respondents, 336 (37.9%) engaged in the clinical treat-ment for PWEs. In the clinical department and workplace of themembers, there were the highest proportions of internal medicinework in clinic. As members of a medical society, most (41.1%)belonged to the Japanese Society of Internal Medicine, while 30(8.9%) belonged to the prefecture's medical association alone. As aninformation source on epilepsy medical care and welfare, most usedmany magazines concerning medicine, while 73 (21.7%) doctors hadhardly obtained information about epilepsy treatment. The rate ofprevalence for epilepsy in the San-in region was estimated to be 8.42per 1000 for 2010.

Conclusion: The present results indicate that it should be important tocarry out medical cooperation between general doctors engaged in thetreatment of PWEs and epilepsy medical specialists. This study was sup-ported by the Japanese Epilepsy Research Foundation.

p500EXPLORING QUALITY OF LIFE IN SLOVAK EPI-LEPSY PATIENTS: A FOCUS GROUP STUDYV. Don�th*, and R. Masaryk�

*F.D. Roosevelt Teaching Hospital, Banska Bystrica, SlovakRepublic; and �Faculty of Education, Comenius University,Bratislava, Slovak Republic

Purpose: The objective of the study was to identify perceptions of qual-ity of life in patients with epilepsy focusing on their experience with thecondition and experience with treatment.

Method: The methods used were focus groups (semi-structured discus-sions moderated by a trained psychologist) and questionnaires. In total 11focus groups were conducted with 54 patients. The average age was 38years (min. 18, max. 72), 56% women and 44% men.

Result: Three areas where epilepsy mostly interferes with the quality oflife as reported by patients were the problem of finding employment

(especially patients with lower qualification), social isolation (exclusion,fear of the disease and stereotypes by others) and problems with claimingdisability benefits. 70% of patients in our sample reported that medica-tions do not fully manage their epilepsy symptoms. Most of the patientshowever perceive social problems associated with the condition to havemuch more severe impact on their quality of life than symptoms associ-ated with epilepsy. As a part of the study findings from inductive analysisof focus group transcripts were compared with medical classification ofseverity of epilepsy symptoms.

Conclusion: In conclusion, the results suggest that there is an urgentneed to create a framework for providing social services and support topatients with epilepsy. Moreover, the welfare system in Slovakia is in thecritical need of readjusting its criteria of providing benefits to suchpatients.

p501PERCEPTION OF EPILEPSY-RELATED HANDICAP ISGREATER IN ‘‘NA�VE’’ POPULATION ACCORDING TOA FRENCH WEB-BASED SURVEY INVOLVING MORETHAN 2000 PERSONSS. Hamelin, L. Vercueil, and A. DepaulisGrenoble Institut de Neurosciences, La Tronche, France

Purpose: Our aim was to study knowledge and perception of epilepsy ina large cohort, and to compare their answers according to their relation toepilepsy.

Method: We developed a web anonymous auto-questionnaire (35 ques-tions) proposed to epileptic patients and independent Email diffusionlists, in France. Answers were collected during a two-months period in2011.

Result: 2047 responses were collected (1421 females and 626 males,mean age 26–35 y.o.). 17% were personally concerned by epilepsy(directly concerned, DC), 67% were indirectly concerned (IC), and 16%were not concerned at any level and did not know persons with epilepsy(not concerned, NC). Self-evaluation of epilepsy knowledge was low(3.2 (NC) to 4.5/10 (DC)). The possibility that epilepsy could occur inneonates or in elderly was mostly unknown, especially in group NC (55and 39%). Treatment was thought to be more restricting by group DC,and 41% of them reported mandatory life-long treatment. The perceptionof the ability of epileptic people to perform all aspects of daily life wasglobally good, mostly up to 4/5, but always better in group DC as com-pared to NC. The more reported handicaps in epilepsy were fear of sei-zure, fear of loss of self-control, and social stigma.

Conclusion: Auto-evaluation of knowledge regarding epilepsy is low,according to this web-based survey, underscoring the need for furthereducation of global population. Interestingly, the perception of epilepsy-related handicap in epilepsy is the greatest in people not concerned byepilepsy.

p502CAN SOCIAL SUPPORT SERVE AS A MEDIATORBETWEEN ILLNESS PERCEPTION AND QUALITY OFLIFE IN PATIENTS WITH EPILEPSY?T. Bar-Adon*, T. Krulik�, I. Bluvstein�, and M. Neufeld�

*Tel-Aviv Medical Center, Tel-Aviv, Israel; �Tel-AvivUniversity, Tel-Aviv, Israel; and �Tel-Aviv Medical Center,Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel

Purpose: To evaluate social support (formal and informal) as a potentialmediator between disease perception and Quality of Life (QoL) inpatients with epilepsy.

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Method: The sample consisted of 80 patients with epilepsy that wererecruited from a tertiary epilepsy center. There were 44 females and 36males, aged 36€13.5 years. Data were collected via 4 questionnaires:socio-demographic, which also included disease severity on a 1–10 Lik-ert scale, brief illness perception, social support, and the Quality of Lifein Epilepsy (QOLIE-31).

Result: Illness perception had a significant negative correlation withQoL (r=-0.597, p<0.001). There was no significant correlation betweensocial support and QoL (r=0.163, p=0.148), however, informal (nuclearfamily) social support positively and significantly correlated with QoL(r=0.315, p=0.004). Social support did not emerge as a mediator betweendisease perception and QoL (b=0.64, p=0.45).

Conclusion: Although in our study, social support could not be consid-ered a mediator between illness perception and QoL in patients with epi-lepsy, there was a positive effect of nuclear family support on their QoL.This finding may be a valuable contribution in the construction of guide-lines for enhancing the QoL in this patient population.

p503INVESTIGATION INTO REPRESENTATION IN FILMOF FIRST PERSON SUBJECTIVE EXPERIENCE OF AGROUP OF PEOPLE WITH EPILEPSYS. AndersonUniversity of the Arts London, London, UK

Purpose: To identify underlying patterns in modes of expression of thesubjective experience of people with epilepsy in a Wellcome Trustfunded film ‘‘What's the Time Mr Wolf?’’

Method: In an interdisciplinary collaboration motivated by studies ofthe representation of epilepsy in film and television (Baxendale S. TheLancet Neurology 2003 Volume 12: Issue 12: 764–770) ten people withepilepsy participated in filmed discussion and accounts of first personsubjective experiences of epilepsy. Documentary and dramatized ele-ments are examined as part of an investigation into the use of film as amedium to articulate the first person subjective experience of the condi-tion.

Result: The perceived third person reactions to epileptic seizures domi-nated accounts by the participants. For the most part, the first person sub-jective was displaced by ‘the other’. The observer or witness - the thirdperson - largely determined the narrative voice of the first person subjec-tive experience of the seizure.

Conclusion: Findings highlight the need to increase public awareness ofepilepsy, given the typically exaggerated and negative third person reac-tions to the altered sense of self during a seizure. Strategies of using filmto construct narratives with positive mechanisms for people with epilepsyare proposed.


p504ICTAL KISSING WITH COMPLEX PARTIAL EPILEPSYAND INFERIOR FRONTAL GLIOSISA. Alsemari, F. Alotaibi, and S. BazKing Faisal Specialist Hospital & Research Centr, PO box 3354,Saudi Arabia

Purpose: Ictal kissing has been described in the literature. Six caseswere reported and associated with TLE and lateralizing to the non-domi-nant hemisphere

Method: A case of ictal kissing was identified. The aim is to demon-strate and discribe the clinical, electro neurophysiologic, surgical proce-dure, histopathological and imaging data.

Result: 29 year sold right-handed female, who has history of epilepsyfor the last 10 years. The patient has no history of febrile convulsions.She has history of an aura of fear followed by automatism of the righthand and left dystonic posturing and lip smacking. This is usually fol-lowed by prolonged emotional gestures, hugging and kissing her relativeand the attendant nurse. The patient has frequency variable from 1–2 permonth. MRI of the brain showed right small cortical and subcorticallesions at the right inferior frontal lobe with gliosis, but without masseffect. The lesion is located directly anterior of the insular gyrus, andmost inferiorly of the inferior frontal gyrus. The hippocampi looked sym-metrical. The PET scan showed hypometabolism of the right temporallobe. Neuropsychology of the patient was showing deficit in her nonver-bal memory. In the Epilepsy unit, 5 push-button events were recorded.The subdural electrodes showed periodic poly spikes discharges over theright inferior frontal region followed by high amplitudes spikes over rightmesial temporal lobe leads. The offsite of the ictal discharges are usuallyat the right frontal strips. Right standard temporal lobectomy with amy-gdalohippocampectomy, with corticectomy and lesionectomy of the rightinferior frontal under neuronavigation guidance was performed. Thepatient continued seizure free. Histopathology of the hippocampus didnot show mesiotemporal sclerosis. The inferior frontal lesion histopathol-ogy was compatible with gliosis.

Conclusion: Our case report supports the findings of the few reportedcases of the ictal kissing behavior lateralized to the non-dominant hemi-sphere. However, the inferior frontal lobe gliotic lesion is a new findingof the affectionate kissing automatisms and may provide a novel under-standing of this stereotyped ictal emotional behavior.

p505VARIANTS OF TRANSFORMATION OF EPILEPTICSEIZURESA. Dubenko, O. Vasilieva, and D. KovalenkoInstitute Neurology, Psychiatry and Narcology AMS of Ukraine,Kharkiv, Ukraine

Purpose: We tried to identify and study the transformation of seizures.Under the term of ‘‘transformation’’ of epileptic seizures (TES), in thepresent study were examined changes in clinical symptoms and changesin the type of attack that could indicate a deterioration of clinical statusand progression of the disease.

Method: The presence of TES studied at 60 patients. 32 patients werehad symptomatic epilepsy, 28 – cryptogenic. This clinical group wasselected after supervision and analysis 320 patients with epilepsy (130 –symptomatic and 190 – cryptogenic). Age of patients was 20–55 durationof epilepsy no less than 1year.

Result: In adult patients can be observed TES. TES are presented forpatients with symptomatic partial epilepsy more frequent than in patientswith cryptogenic epilepsy. Changes in clinical seizures, which were char-acterized by disease progression, increase of mental and neurological dis-orders, and deteriorating quality of life of the patient, transformationrefers to the ‘‘negative’’. If the change in the clinical picture of seizureswas accompanied by improvement of the run of the disease - recorded‘‘positive’’ transformation. 32patients had ‘‘negative’’ transformations,28 - ‘‘positive’’ ones.

Conclusion: The study of the character TES is an important, accessibleand objectified criteria for assessing of epilepsy activity, the adequacy ofantiepileptic therapy, the subsequent prognosis.

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p506CLINICAL, VIDEO-EEG AND NEUROIMAGING STUDYOF DRUG-RESISTANT FOCAL EPILEPSY ASSOCI-ATED WITH HAMARTOMA OF THE FLOOR OF THEFOURTH VENTRICLEG. Rubboli*, L. Volpi�, M. Maffei�, F. Marliani�, P. Riguzzi�,S. Zoboli�, G. Faggioli�, F. Santoro�, E. Pasini�, andR. Michelucci�

*Epilepsihospital, Filadelfia, Dianalund, Denmark; �IRCSSInstitute of Neurological Sciences, Bologna, Italy; and �NuclearMedicine Unit, Bologna,

Purpose: Hamartomas of the floor of fourth ventricle (HFFV) are extre-mely rare entities that can be associated with repetitive attacks of hemifa-cial spasm. Intralesional EEG recordings of epileptic discharges and ictalSPECT suggested seizure onset within the hamartoma. This study aimedto extensively investigate the clinico-neurophysiological-neuroimagingfeatures of a patient with drug-resistant focal epilepsy associated withHFFV.

Method: A 20 years-old female patient with drug-resistant focal motorseizures of the right hemiface, occurring several times per day since 6months of age was admitted to Epilepsy Monitoring Unit for evaluationof a drug-resistant focal epilepsy. A detailed clinical history was taken.She underwent awake and sleep EEG/polygraphy, long-term video-EEGmonitoring (LTVEEG), 3 Tesla MRI (3T-MRI), interictal and ictalSPECT, neuropsychological assessment.

Result: Interictal awake and sleep EEG/polygraphy did not show epilep-tiform abnormalities; during sleep, polygraphy revealed periodic muscletwitches of the right orbicularis oris without EEG correlate. LTVEEGshowed focal seizures, occurring several times per day characterized byright eye blinking, myoclonic twitches of the right hemiface sometimesspreading to the neck with right head deviation. Ictal EEG did not showclear-cut epileptiform discharges (Video-EEG data will be presented).3T-MRI showed right HFFV. Interictal/ictal SPECT was inconclusive.Neuropsychological assessment was unremarkable.

Conclusion: Our data contributes to furtherly define the rare conditionof focal epilepsy associated with HFFV. Ictal LTVEEG data supportedthe hypothesis of the main activation of brainstem nuclei by the epilepticdischarge originating from HFFV, with a mechanism possibly analogousto hypothalamic amartoma.

p507TUBULIN GENES IN HUMAN DISORDERS OF CERE-BRAL CORTEX DEVELOPMENTT. D. Cushion*, J. G. J. Mullins*, S. Chung*, R. J. Harvey�,W. B. Dobyns�, D. T. Pilz§, and M. I. Rees–

*Swansea University, Swansea, UK; �UCL, London; �SeattleChildren's Hospital, Seattle, WA, USA; §Wales EpilepsyResearch Network, Swansea, UK; and –Institute of Life Science,Swansea, UK

Purpose: The development and correct function of the mammalian cere-bral cortex is dependent on the precise arrangement of neurons to assem-ble its characteristic laminar structure. Lissencephaly (LIS) andPolymicrogyria (PMG) are devastating neuronal migration disorders co-morbid with severe epilepsy, intellectual and physical disabilities. Thesedisorders arise when the regulation of cell migration in the developingcerebral cortex is disturbed. This study describes the role of tubulin genes(TUBA1A and TUBB2B) in disorders of cortical development.

Method: LIS and PMG patient DNA from UK and US Centres wasscreened for TUBA1A and TUBB2B mutations by direct sequencing.Variants were functionally analysed to assess the effects on Microtubule

(MT) dynamics, in vitro. C-terminally FLAG-tagged tubulin expressionconstructs were transfected into HEK293 and PC12 cell lines.

Result: Three novel and one recurrent TUBA1A sequence variationswere identified in the LIS patient cohort and one genetic variant wasidentified in a patient with PMG. Four novel TUBB2B sequence variantswere also identified in PMG patients. All variants identified were hetero-zygous de novo that translated into missense amino acid substitutions.Incorporation of these mutants into the MT cytoskeleton was observed incomparison to wild-type, followed by morphometric analysis and MTpolymerisation assays. Homology models of tubulin mutants were gener-ated to predict the consequences of the residue substitutions on proteinconformation.

Conclusion: TUBA1A and TUBB2B mutations are present in cohortindex-cases confirming their role in cortical malformation syndromes.We present significant evidence of in silico and in vitro data confirmingthe protein damaging effects of these mutations.

p508A PORTABLE DEVICE FOR INVESTIGATING AUTO-MATED SEIZURE ABATEMENT IN HUMANS USINGELECTRICAL STIMULATIONA. Lai*, M. Cook�, T. S. Nelson*, D. B. Grayden�,C. E. Williams*, and P. Blamey**Bionics Institute, East Melbourne, Vic., Australia; and �TheUniversity of Melbourne, Melbourne, Australia

Purpose: To develop a portable device to investigate automated seizureabatement using electrical stimulation in patients with refractory epilepsyundergoing intracranial EEG monitoring for pre-resective assessment.The portable system simplifies deployment and enables data collectionfrom multiple epilepsy centres to mitigate logistical limitations with con-ducting research on these patients. These limitations include a relativesmall number of patients being assessed per annum at any centre due tothe resource intensiveness of these studies, with assessment periods oftenlimited to one week to minimise infection risk, research paradigms areonly initiated after sufficient clinical information is obtained, andpatients may have few seizures during monitoring.

Method: A portable device was specifically designed and constructed toinvestigate automated seizure abatement using electrical stimulation inepilepsy patients. The research system consists of a wireless EEG acqui-sition device, a custom built stimulator with a switch array that can routeindividual electrode connections to either the EEG acquisition device orthe stimulator, and a tablet PC that runs the EEG acquisition software andseizure detection to trigger the therapeutic stimulation, as well as control-ling the stimulation paradigm. The device was designed to be compatiblewith different electrode configurations and capable of reprogrammingfor evaluating different stimulation/detection paradigms.

Result: The portable research device has evolved from our modular trol-ley mounted research setup and serves as a proof of concept for animplantable automated seizure abatement device.

Conclusion: A portable device has been developed to simplify andenhance further investigations on automated seizure abatement inhumans using electrical stimulation.

p509FOCAL CORTICAL DYSPLASIA TYPE IA AND PARV-ALBUMIN STAINING IN TEMPORAL LOBE EPILEPSYG. Kuchukhidze*, I. Unterberger*, G. Luef*, M. Ortler*,A. Wieselthaler-Hçlzl*, A. J. Becker�, E. Trinka�, and G. Sperk**Medical University of Innsbruck, Innsbruck, Austria; �Institutefor Neuropathology, Bonn, Germany; and �Paracelsus MedicalUniversity, Salzburg, Austria

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Purpose: Alterations in GABA-ergic cortical neuronal system havebeen reported in FCD type Ia, a malformation of cortical developmentassociated with of pharmacoresistant epilepsy. We aimed to analyseparvalbumin (PV)-immunoreactive interneurons in 19 patients with phar-macoresistant temporal lobe epilepsy (TLE) and FCD type Ia affectingtemporal lobe. We compared our findings with those in cortical surgicalspecimens of 20 TLE patients who underwent the resection of anteriortwo-third of a temporal lobe due to hippocampal sclerosis (TLE-HS) aswell as 8 post-mortem controls.

Method: Routinely stained slides and serial sections for neuron-specificnuclear protein (NeuN) and PV were analysed. The density of inhibitoryPV-immunoreactive interneurons was quantitatively assessed in allpatients and controls by using a two-dimensional cell-counting tech-nique. The following three parts of temporal cortex and white matterwere assessed separately in all groups: 1) cortical layers 1 through 4, 2)cortical layers 5 and 6, and 3) subcortical white matter (WM).

Result: The density of PV-immunoreactive interneurons was signifi-cantly higher in patients with FCD type Ia compared to those with post-mortem controls in all cortical layers and WM. There were significantlymore PV-immunoreactive interneurons in FCD type Ia compared toTLE-HS in cortical layers 1 through 4 and WM. TLE-HS had signifi-cantly larger numbers of PV interneurons compared to post-mortem con-trols only in cortical layers 1 through 4.

Conclusion: The increased number of PV positive, presumably inhibi-tory interneurons in FCD type Ia compared to TLE-HS and post-mortemcontrols may suggest a possible compensatory mechanism against ongo-ing seizure activity.

p510LAYER SPECIFIC GENES EXPRESSION IN PATIENTSWITH FOCAL CORTICAL DYSPLASIA TYPE IIL. Rossini*, R. Garbelli*, L. Tassi�, M. Cossu�, andR. Spreafico**I.R.C.C.S. Foundation Neurological Institute, Milan, Italy; and�Niguarda General Hospital, Milan, Italy

Purpose: Focal Cortical Dysplasia Type II are malformation of corticaldevelopment frequently associated with intractable epilepsy and charac-terized by cortical dyslamination and abnormal cell morphology (dys-morphic neurons and balloon cells). While balloon cells seem to arisefrom radial glial stem cells and show immature phenotype, dysmorphicneurons express markers indicative of origin from radially migratingpyramidal neurons and express markers of neuronal maturity. The patho-genesis of FCD and the origin of these cytological abnormalities, has notbeen clearly established. Aim of this work is to investigate the origin ofthese abnormalities by means of layer-specific genes expression inhuman surgical tissue presenting a neuropathological diagnosis ofFCDII.

Method: We performed RNA in situ hybridization (ISH) on 16 FCDIIcases using a panel of cortical layer-specific markers, whose expressioncovers all cortical layers: Cux2, Ror-b, Er81, Nurr1 respectivelyexpressed in layers II-III, IV, V and VI. Moreover, double ISH andimmunocytochemistry using SMI and Vimentin antibodies were per-formed.

Result: Layer specific genes expression pattern, inside lesion, reveals acomplete disruption of laminar organization. Concerning cytologicalabnormalities, Cux2, Ror-b, Er81 and Nurr1 are expressed in both dys-morphic and balloon cells, with a high grade of variability for each ana-lyzed case.

Conclusion: The complete cortical re-distribution of the layer specificgenes expressing neurons differ not only from a ‘‘normal’’ pattern butalso from the less altered pattern typical of FCDI. The different expres-sion of layer specific markers in dysmorphic and balloon cells might indi-cate their origin at different time windows during cortical development.

p511EPILEPSY AND DEVELOPMENTAL OUTCOME ININFANTS AND CHILDREN WITH STURGE-WEBERSYNDROME (SWS)S. E. Aylett*, and P. Rankin�

*Great Ormond Street Hospital NHS Trust and UCL Institute ofChild Health, 3JH, UK; and �UCL Institute of Child Health,1EH, UK

Purpose: To define the severity of the epilepsy and cognitive outcomein infants and children with SWS.

Method: Case notes review of Infants and children with SWS attendinga specialist tertiary multidisciplinary clinic.

Result: 50 children, with full data sets available for 45 were followed:age at review 2 months-17 years (mean 5 years, 9 months). 45 (90%)had developed epilepsy;21 (42%) had received regular aspirin prophy-laxis. The pial angioma was unilateral in 38 (22 left, 16 right) andbilateral in 12. The Mean Developmental or Intellectual Quotient was60 (Standard deviation 30). The age at epilepsy onset was birth to 12years (mean 16 months, standard deviation 30 months). 30 (66%) hadat least 1 episode of status epilepticus. Severe clusters of seizuresoccurred in 29 (64%). Seizures resulting in an acquired hemiplegiaoccurred in 17 (38% of the epilepsy population) 0.12 (27% of epilepsypopulation) proceeded to neurosurgical treatment of their epilepsy.10(22% of epilepsy population) no longer had seizures 6 months prior toreview and 3 (7%) were no longer on antiepileptic drug treatment atthe time of review.

Conclusion: Sturge-Weber syndrome is associated with the onset of epi-lepsy in the first 2 years of life and frequently associated with status epi-lepticus and an acquired hemiplegia. Infants and children have a variabledevelopmental and cognitive outcome.

p512FATAL POST-ICTAL VENTRICULAR FIBRILLATIONIN A PATIENT WITH COMPLEX PARTIAL SEIZURES:A CASE REPORTL. LeungKing's College Hospital, London, UK

Purpose: This case report describes a patient with a background of wellcontrolled complex partial seizures who developed an episode of com-plex partial seizure whilst recovering from an uneventful, elective percu-taneous coronary intervention (PCI). The patient subsequently had apost-ictal ventricular fibrillation cardiac arrest. The outcome given wasSUDEP. This case and current evidence are discussed.

There are no case reports on post ictal VF (ventricular fibrillation);this case is also one of SUDEP (sudden death in epilepsy) in a patientwith well controlled epilepsy and post uneventful cardiac intervention,which is unusual.

Method:

Case presentation: An 80 year old Greek lady presented to our cardiol-ogy department for an elective PCI. She had a background of lifelong epi-lepsy- complex partial, well controlled with carbamazepine. Her lastseizure was over 1 year ago. She was also Type 2 diabetic with knowncoronary artery disease- with 2 previous recent PCI procedures. Theactual procedure was uneventful but she had an episode of complex par-tial seizure afterwards and soon after whilst in the post ictal phase devel-oped fatal VF, which she did not survive. The coroner's verdict was oneof SUDEP, with no evidence of procedure related cardiac arrest.

Result: A negative bundle of investigations peri-event included: bedsideechocardiograms, 12 lead ECGs and blood profile.

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Conclusion: This is a case report that adds to the growing study of epi-lepsy and arrhythmias of which some can be fatal. This case of SUDEP inparticular occurred in the context of post cardiac intervention and wellcontrolled epilepsy.


p513IMPACT OF PERI-ICTAL INTERVENTIONS ON RESPI-RATORY IMPAIRMENT AND POST-ICTAL GENERAL-IZED EEG ATTENUATIONM. Seyal, and L. M. BatemanUniversity of California Davis, Sacramento, CA, USA

Purpose: Seizure-related respiratory dysfunction (RD) and duration ofpost-ictal generalized EEG suppression (PGES) may be important in thepathophysiology of sudden unexpected death in epilepsy (SUDEP). Weassessed the impact of peri-ictal nursing interventions on RD and PGESduration in consecutive patients with localization-related epilepsy andsecondarily generalized convulsions (GC) recorded during video-EEGtelemetry.

Method: Nursing interventions including administration of supplemen-tal oxygen, oropharyngeal suction and patient repositioning were evalu-ated. Two-sided Wilcoxon signed-rank test was used to compare all GCwith and those without intervention. Robust linear regression was used toassess the association between timing of intervention and duration ofhypoxemia (SaO2 <90%) and PGES duration using data from only thefirst GC for each patient.

Result: There were 39 patients with 105 GC. Oxygen desaturation dura-tion data was available for 34 patients. PGES >2 seconds occurred fol-lowing GC in 16 patients. There were 21 GC with no intervention and 84GC with interventions. Seizure or convulsion duration was not signifi-cantly different between the two groups. PGES did not occur in the no-intervention group. Desaturation duration was longer (p<0.0001), SaO2nadir lower (p=0.0086) and end-tidal CO2 higher (p=0.0027) in the inter-ventions group compared to no-intervention group.

In the group with nursing interventions, earlier intervention was asso-ciated with shorter duration of oxygen desaturation (p<0.0001) andshorter duration of PGES (p=0.0012).

Conclusion: Nursing interventions occurred in seizures with PGES andmore severe RD. Earlier intervention was associated with reduced dura-tion of RD and PGES. These findings should be considered when devel-oping measures to reduce SUDEP risk.

p514STUDY OF PREGNANT WOMEN WITH EPILEPSY INBRAZIL: INITIAL RESULTSC. S. M. G. Miziara, V. A. G. Serrano, M. L. G. Manreza,S. D. L. G�is, and D. H. NakanishHospital das Cl�nicas of Medicine University os S¼o Paulo, SaoPaulo, Brazil

Purpose: The effects of fetal exposure to antiepileptic drugs (AED)have been described frequently. However, in Brazil there are few studiesabout it. The aim of this study was to analyse over four years (2008–2011) the type of delivery and the condition of newborn babies.

Method: This prospective and observational study was performed in theClinical Hospital of S¼o Paulo Medical School, Brazil

Result: 64 newborn babies of women with epilepsy were evaluated, thematernal age ranged between 15 and 38 years, only 11 (17%) mothershad taken folic acid before pregnancy, 34 were taking one AED, 19 twoor more AED e 11 were drug free. The minority of them showed worsen-ing in seizure frequency (23%). The deliveries were cesarean (48%), nor-mal (44%), and forceps (8%). 31 children were male and 33 female. Therate of prematurity was 19%. The number of underweight children was17%, and the number of malformations was 8/64. The most common mal-formations were: cardiac and minor malformations. In this study therewas no difference between mono and polytherapy. Only three mothershad taken folic acid of these children with malformation.

Conclusion: The frequency of children with malformations (12.5%)was higher than that described in the literature; however one explanationfor this event could be the fact that pregnant women with refractory epi-lepsy were screened for our hospital, center of reference in epilepsy. Inaddition most pregnant women were not taking folic acid, which mayalso have contributed to the high number of malformed children.

p515WOMEN'S EPILEPSY AND ANTIEPILEPTIC DRUGSSIDE EFFECTS ON REPRODUCTIVE HEALTHG. V. Odintsova*, N. Y. Koroleva*, A. A. Chugunova*, andL. A. Saukova�

*Institute of Human Brain of RAS, Saint Petersburg, RussianFederation; and �Medical University, Saint Petersburg, RussianFederation

Purpose: To investigate the frequency of reproductive endocrine disor-ders (RED) for female epilepsy in association with the type of antiepilep-tic therapy (AEDs).

Method: 155 women of reproductive age were enrolled in a prospectiveobservational single-center uncontrolled comparative study of the AEDsside effects on reproductive health in 3 groups: 1gr.-monotherapy AEDs,2gr. - polytherapy, 3g. – no AEDs used. The diagnosis was establishedbased on comprehensive exam, in accordance with ICD-10. NaranjaAlgorithm was used to determine reliability of communication ‘‘AEDs -RED’’.

Result: 70 patients (45%) were in 1 gr, 65 (42%) – in 2gr, 20 (13%) – in3 gr. The overall incidence of RED were 53%, 75% of them due to sideeffects of AEDs. Comorbid RED was observed in 21 (13%). In 61 (40%)cases RED were identified due to treatment of AEDs. 1 group - 40patients were healthy (57%). In 21 (30%) - REN were associated with thetaking AEDs. Comorbid RED was identified in 9 (13%). 2group - 19patients (29%) didn't have a RED. Comorbid RED was observed in 9patients (12%). RED associated with exposure to AEDs, was diagnosedin 38 patients (59%). 3group - 14 persons (70%) were healthy. ComorbidRED was diagnosed in 4 (20%). The 2 (10%) - retained menstrual irregu-larities arising from preceding AEDs. Differences in the frequency ofRED in the comparison groups were statistically significant (p <0.001).

Conclusion: The RED are a frequent side effect of AEDs therapy. Useof AEDs in females requires the monitoring of reproductive health.

p516‘OPTION GRID’ DECISION-SUPPORT INTERVENTIONFOR WOMEN TAKING SODIUM VALPROATE ANDPLANNING PREGNANCYP. Smith, R. Seal, and G. J. ElwynUniversity Hospital of Wales, Cardiff, UK

Purpose: Sodium valproate, normally recommended to treat geneticgeneralized epilepsies, is teratogenic and so not suitable for of child-bear-ing potential. Women already taking valproate should be involved in the

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decision as to whether to change treatment. We have designed a decisionsupport intervention, an ‘option grid’, to aid this process.

Method: We identified relevant options and answers to frequently-asked questions using the 2012 NICE guidelines, literature reviews andemailed consultations with experts in the field, so gaining maximum clin-ical consensus. Having developed an evidence document and drafted the‘option grid’, we refined this further through consultation with localhealthcare workers in the field of epilepsy.

Result: We identified sodium valproate, levetiracetam and lamotrigineas the relevant treatment options. We chose five frequently-asked ques-tions (FAQs), broadly addressing seizure control, teratogenicity, andadverse effects. We wrote answers to these FAQs in an Option Grid withan accompanying evidence document.

Conclusion: The option grid and evidence document should helpwomen, with their clinicians, decide their best treatment option.

p517GLUTAMIC ACID DECARBOXYLASE ANTIBODY: ALINK FOR LOCALISATION RELATED EPILEPSY,STIFF-PERSON SYNDROME AND TYPE I DIABETESMELLITUS? REPORT OF TWO CASESG. Barcs*, A. Szucs�, and A. Kamondi**National Institute of Neurosciences, Budapest, Hungary; and�Budapest, Hungary

Purpose: Antibodies to glutamic acid decarboxylase (GAD) aredetected in about 80% of newly diagnosed type I diabetes mellitus(DM1) patients. High GAD antibody levels are present in up to 80% ofpatients with stiff-person syndrome (SPS). Epilepsy affects 10% ofpatients having SPS with GAD antibodies. We wanted to call attention tothe possible GAD-related mechanism of epilepsy as well as to the GAD-link of DM1, SPS, and epilepsy.

Method: We present the history of two personal cases demonstratingthe mechanism and link in question. Both had partial epilepsy, type I dia-betes mellitus and stiff-person syndrome; and both had high serum GADantibody levels.

Result: In the several years’ history of both patients the three conditionshad the same time sequence: firts partial epilepsy developed, it was fol-lowed in years by DM1, and finally SPS has appeared. In one patientplasma apheresis performed in a relatively initial period of SPS provedbeneficial in that condition, improving the effect of pregabaline and ben-zodiazepine.

Conclusion: Our cases support the observation that GAD antibody maybe associated with partial epilepsy; not only with DM1 and SPS.

p518THE AIM OF WORK WAS TO STUDY THE CONTENTNEUROAMINOACIDS (NAC) IN WHEY OF BLOODPATIENTS WITH TRAUMATIC BRAIN INJURY (TBI)WITH A CONVULSIVE SYNDROMEI. I. ChernenkoKharkiv Medical Academy of Postgraduate Education, Kharkiv,Ukraine

Purpose: The aim of work was to study the content neuroaminoacids(NAC) in whey of blood patients with traumatic brain injury (TBI) with aconvulsive syndrome.

Method: We examined 42 patients with TBI at the age of 23 to 65 years.The level of NAC was determined in the first days after TBI received.

The first group consisted of 20 persons moderate TBI with convulsivesyndrome, mean age 53.39 years, the second - 22 people with mild TBIwith a convulsive syndrome, mean age 52.71 years. The groups werecomparable in age, sex.

Result: The study revealed that patients with mild TBI level of excit-atory NAC (glutamic - 1145 € 0.24 mg, aspartic - 0228 € 0.05 mg) weresignificantly higher than in patients with moderate TBI with convulsivesyndrome (0.805 € 0.07 mg and 0.164 € 0.02 mg, respectively), p<0.05.At the same time, there was a trend to an increase in brake NAC inpatients with mild TBI with a convulsive syndrome compared withpatients with moderate TBI with a convulsive syndrome (glycine - 1427€ 0.13 mg and 1345 € 0.19 mg respectively, proline - 1556 € 0.24 mg isthe 1211 € 0.17 mg, respectively), p>0.05.

Conclusion: Thus, patients with mild TBI with a convulsive syndromemarked by an imbalance of NAC: NAC increase in excitatory (glutamate,aspartate) and a tendency to increase the level of brake NAC (glycine,proline) compared with patients with mild TBI with convulsive syn-drome.

p519EPILEPSY IN PRADER-WILLI SYNDROME; THEISRAELI EXPERIENCET. Gilboa, and V. Gross-TsurShaare Zedek Medical Center, Jerusalem, Israel

Purpose: Prader-Willi syndrome (PWS) is a rare neurogenetic systemicdisorder (1:10,000 to 25,000 live births) characterized by severe cogni-tive, behavioral and physical disabilities. It is caused by a deletion (70%)in the paternally inherited chromosome 15q11-q13, maternal UPD (25%)in the same region or mutations in the imprinting center (IC, 5%) withinthat area. Recently, 16–26% of PWS patients were reported to have sei-zures. Our goal was to assess the frequency and characteristics of epi-lepsy in the Israeli cohort of PWS patients.

Method: After the approval of the institutional review board, informa-tion regarding epilepsy was obtained from 116 individuals with geneti-cally confirmed PWS. A detailed questionnaire was completed followingan interview with caregivers and medical chart review. Fifty-three sub-jects underwent EEG.

Result: One hundred and sixteen questionnaires were completed (110interviews, 116 charts reviewed). Sixteen patients had seizures, 7 (6%)epilepsy, 1 single seizure, and 8 (6.9%) febrile seizures only. There was atrend towards association between seizures, both non-febrile and febrile,and the deletion subtype (p=0.055). Fifty-three individuals, ages 4m-48y(mean 12.8y), underwent EEG. Patients with epileptogenic EEGs (9/53patients, 6/9 deletions and 3/9 UDP) were relatively young (mean age5.5y, p=0.02). Focal epileptic discharges were seen in 9/53 (ages 5m–13y, mean 5.5 years), with electrographic seizures recorded in 3/53. Nopatient had active epilepsy or received treatment.

Conclusion: The prevalence of epilepsy in our cohort is low but EEGabnormalities approached 17% and electrographic seizures 5%. RoutineEEG is advocated especially in the younger age group and in those withdeletions.

p520CARDIAC ASYSTOLE WITH SYNCOPE AS A FIRSTMANIFESTATION OF EPILEPSYA. Rakitin, M. Liik, and S. HaldreTartu University Clinic, Tartu, Estonia

Purpose: Cardiac asystole provoked by epileptic seizures is a rare butimportant complication in epilepsy. Usually, ictal asystole occures inpatients with long history of focal epilepsy and is observed principally in

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left-sided epilepsies. The purpose of this report is to show that syncopecaused by asystole could be the first manifestation of epilepsy.

Method: A case report of 65-year-old, previously healthy female whowas admitted in hospital for a transient loss of consciousness.

Result: An electroencephalogramm (EEG) was performed. During theEEG, the patient had an ictal episode and a contemporary severe brady-cardia leading to asystole. EEG showed an ictal pattern characterized byrhythmic 5Hz theta activity confined to the right frontal region. Five sec-onds after the beginning of the ictal episode the electrocardiogramm(ECG) showed a progressive bradycardia followed by complete sinusarrest that lasted 30 seconds. The asystole led to generalized slownessand was correlated with an extended EEG depression at the end of the ic-tal event. During this event, patient clinically had syncope with an apnoeand increase of facial muscle tone.

Conclusion: Cardiac asystole may be the first manifestation of focal epi-lepsy. The right frontal lobe structures may play a role in autonomic regu-lation of cardiovascular responses.

p521QUALITY OF LIFE IN OLDER ADULTS WITH EPI-LEPSYA. Velez-Van-Meerbeke*, P. Quintero-Cuzquen�, C. AlbertoGalvis-Gomez*, and G. Guzman**Universidad Del Rosario, Bogota, Colombia; and �Hospital dela Samaritana, Bogota,

Purpose: To evaluate the quality of life in patients 65 years or older withactive epilepsy in two hospitals in Bogot�, Colombia.

Method: The clinical charts including the electroencephalogram anddiagnostic images of 120 patients were reviewed. Then the QOLIE-31and version 10 of Minimental Tests were used to establish the patient'squality of life score and his cognitive level. Global quality of life and sub-scales scores were correlated with quantitative variables using the Spear-man coefficient and differences between qualitative variables wereevaluated with non-parametric tests. To establish the variables thatexplained the quality of life, we used an ordinal regression model. Thisstudy was approved by the Research Ethics Committee of both hospitals.

Result: 106 patients of both sexes with an age of 71.9€6.32 years werestudied. Epilepsy began at 61.92€16.5 years and only 4% of patients wereseizures free for the past two years. 88.7% had focal seizures and if anunderlying etiology was identified, cerebral vascular disease was pre-dominant. 71% were on Phenytoin monotherapy. Global quality of lifescore was 52.17€15.83. It was affected by number of seizures, Mini-men-tal test score, educational level, socioeconomic status and MRI abnor-malities. Other variables such as gender, housing site, job, type ofseizures, availability of AED and treatment with phenytoin influencedQOLIE subscales.

Conclusion: Quality of life is an individual perception that could beinfluenced by many factors. Patients over 65 years of age with epilepsyusually show a poor quality of life not only related to the disease but alsoto their socioeconomic conditions.

p522DIAGNOSING AND TREATMENT OF EPILEPSY INTHE ELDERLYG. A. Kiteva-TrencevskaUniversity Clinic of Neurology, Skopje, Macedonia

Purpose: Despite increasing incidence of new-onset epilepsy amongelderly, there are reports of delay in their diagnosis and treatment. The

aim is to analyze the seizures and epilepsies in the elderly and report theirtreatment.

Method: 51 patient aged 60–83 years with epilepsy were analyzed clini-cally and with: laboratory analysis, EEG, evoked potentials, brain CT/MRI, ultrasound of carotid and vertebral arteries, neuropsychologicalevaluation, consultation with internal medicine, neurosurgery and oncol-ogy specialists appropriately.

Result: Provoked seizures were found in 7 patients and they were nottreated as epilepsy. Cryptogenic focal epilepsies were found in 12patients, most of them with vascular risk factors: diabetes mellitus,hypertension, hypercholesterolemia. Focal symptomatic epilepsies werefound in 27 patients: 3 with post-traumatic epilepsy, 6 with cerebraldegenerative changes, 9 with cerebral neoplasm, 6 primary and 3 meta-static and 9 post-stroke epilepsy. Idiopathic generalized epilepsies withseizures after the age of 60 years while on AEDs were found in 5 patients.Differential diagnostic possibilities in elderly patients with epilepsymade the diagnosis of epilepsy a challenge. Most of the patients were onAED treatment. AEDs were selected towards individual needs of eachpatient, considering the pharmacodinamics, pharmacokinetics of AEDsand patient's comorbidity. Surgery with additional AEDs was used fortreatment of patients with operable brain neoplasm and ruptured cerebralaneurism.

Conclusion: Awareness of increased incidence of epilepsy in theelderly, different clinical manifestations imitating other somatic/neuro-logical conditions is a need for appropriate treatment of epilepsy in theelderly reducing their morbidity and mortality.


p523OPTIMIZING PATIENT CARE AND MEDICAL EDUCA-TION THROUGH AAN EPILEPSY QUALITY MEA-SURES IN A UNIVERSITY HOSPITALJ. M. Cisneros-Franco*, M. A. Gutierrez-Herrera�,J. B. Rodr�guez-CastaÇeda*, J. M. Mart�nez-Valenciano*,L. L. Huerta-Esquivel�, J. L. Gonz�lez-Garza�, and M. A. D�az-Torres�

*Universidad Aut�noma de Nuevo Le�n, Monterrey, Mexico;and �Hospital Universitario-UANL, Monterrey, Mexico

Purpose: The American Academy of Neurology & Physician Consor-tium for Performance Improvement (AAN/PCPI) suggested eight qualitymeasures to be observed at every patient visit. Our aim is to compare thepercentage of adherence to each measure before and after the implemen-tation of a new worksheet in a referral center in north-eastern Mexico.

Method: Interventional study including medical records filled by medi-cal school seniors and junior residents supervised by an epileptologist.We included 104 consecutive people with epilepsy, evaluated before andafter updating our clinic visit form, from November 2011 through mid-February 2012. McNemar change test was used to compare the percent-ages of observance for AAN/PCPI standards –i.e., seizure type and fre-quency, etiology, EEG, MRI/CT scan, AED side effects, surgical therapyreferral, safety counseling, counseling for women with childbearingpotential– and physical exam. Each quality measure was considered to befulfilled only if it was assessed and properly recorded.

Result: Mean age was 34.7 (€14.5), 52.9% women, epilepsy onset atage 19.8 (€15.4), 78.1% presented with partial-onset seizures. All qualitymeasures improved (previous vs new), reaching statistical significancefor safety counseling 7.9vs55.4% and physical exam 60.6vs94%(p<0.01). The remaining increases were as follows: seizure type84.8vs92.8%, frequency 50vs57.8%, etiology 69.7vs81.9%, EEG

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62.7vs75.6%, brain imaging 44.1vs59.8%, adverse effects 10.8vs19.5%,childbearing counseling 16vs47.2%. Two patients were referred to pre-surgical evaluation.

Conclusion: These preliminary results suggest that a quality-orientedepilepsy worksheet plays a role in improving the adherence to AAN/PCPIproposed standards, notably for safety counseling; thus enhancing medi-cal education and, more importantly, our patients’ care.

p524LONGTERM OUTCOME BEYOND 20 YEARS IN 66PATIENTS WITH JUVENILE MYOCLONIC EPILEPSYP. Senf, B. Schmitz, M. Holtkamp, and D. JanzVivantes Humboldt Klinikum, Berlin, Germany

Purpose: JME is the one of the most common IGE subsyndrome, but lit-tle is known about the long term outcome. The aim of this study was theanalysis of the longterm outcome of a series of JME patients.

Method: Out of 339 records of patients with IGE from the Janz-Archiveof the Charit� Department of Epileptology, 66 patients (10.2%) matchedthe inclusion criteria. Minimum follow-up time was 20 years, remissionwas defined by a minimum of five years seizure freedom.

Result: We enrolled 66 patients with a mean current age of 62.4 yearswho had been followed up for a mean of 44.6 years. A total of 39 patientshad become seizure free (60%), 45 years after diagnosis. Among seizurefree patients 28 (43.1%) were still taking AED, and 11 were off medica-tion (17.5%). From 27 patients without remission (40.9%), 11 (40.7%)reported, to have had seizure-free times > 5 years in the past. 16 (59.3%)showed a poor course with no seizure - free time longer than 5 years sofar. 54 were still taking AED, 38 in Monotherapy (70.4%) and 16 in Poly-therapy (29.6%). Absence seizures appeared significantly more often inthe patient group without remission (p = 0.009).

Conclusion: This study analyses the long term outcome of a welldefined sample of patients with JME. Seizure remission occurred in 60%of patients, 17.5% remained seizure free without AED. Appearance ofabsence seizures was an attribut for a poor course with ongoing seizureswithout remission (p=0.009).

p525ELECTROCLINICAL FEATURES IN EPILEPSYCAUSED BY VOLTAGE GATED POTASSIUM CHAN-NEL ANTIBODIESN. Mullatti*, K. Kioulachidis�, N. Moran*, S. Goyal�, andM. Lim�

*Kings College Hospital, London, UK; �King's College, London,UK; and �Evelina Children's Hospital, London, UK

Purpose: VGKCA related epilepsy is a relatively new autoantibody syn-drome presenting subacutely with seizures, cognitive impairment andvariable neurological involvement. The electroclinical features of thisentity are not well described, and our understanding of this condition stillevolving. The aim of this paper is to describe the electroclinical featuresof the seizures with adult and pediatric presentation.

Method: 12 patients (9 adults and 3 children) who were diagnosed withVGKCA related illness are presented. All patients underwent neurologi-cal evaluation, MRI scans, EEGs and VideoTelemetry, CSF, Autoanti-body testing and Neuropsychology. The clinical course of the illness, thetype of treatment, and the response to it were studied.

Result: All adult patients presented with seizures, neuropsychiatric fea-tures with cognitive, memory, and behavioral problems. All patients hadpositive VGKC antibodies from low titres to high, and all showed clinicaland neuropsychological improvement with treatment.

Conclusion: The spectrum of the electroclinical manifestations relatedto this entity may vary significantly and is not well defined yet. It isapparent that along with seizures a complex cognitive profile of distur-bances is present. EEG findings are mainly encephalopathetic, and MRIimages show a signal abnormalities in the limbic area. In contrast, thefeatures in paediatric patients are more severe, in the context of status ep-ilepticus and intractable seizures. Appropriate treatment results in vary-ing degrees of clinical recovery.

p526FEATURE COMPARISON FOR REAL-TIME DETEC-TION OF NOCTURNAL SEIZURES USING ACCELE-ROMETRYC. Ungureanu*, M. Van Bussel*, I. Y. Tan�, J. B. A. M. Arends�,and R. M. Aarts�

*HOBO Heeze, VE, The Netherlands; �Kempenhaeghe, Heeze,The Netherlands; and �Eindhoven University of Technology,Eindhoven, The Netherlands

Purpose: It is important to monitor in real-time patients with convulsiveepileptic seizures. Especially nocturnal seizures are at risk of going unno-ticed.

Method: Accelerometry among other techniques can provide an effec-tive tool to accomplish the above goal. The small size of the accelerome-ter and new wireless based technologies are strong points towardsdeveloping portable devices to detect convulsive seizures. We studiedthe discriminating power of the mostly used features derived from accele-rometry. Additionally we present a new method to determine the thresh-olds for classification derived from non-seizure movement patterns of thepatient. Finally we evaluate the features and classification method ondata recorded on 18 patients (> 60 seizures) having a broad spectrum ofconvulsive epileptic seizures.

Result: We show that features derived from the amplitude of the signalhave a lower discriminating power in comparison with the ones derivedfrom the phase. Also, relatively simple computation efficient featurescorroborated with the classification method introduced by us providegood results.

Conclusion: Our research points out that two accelerometer sensors rep-resent a minimum requirement for the detection of nocturnal convulsiveseizures.

p527ACUTE ENCEPHALITIS WITH REFRACTORY REPETI-TIVE PARTIAL SEIZURES (AERRPS): PRESENTATIONOF THREE CHILDREN CASESV. I. Venegas*, M. Hernandez�, and C. Alvarez�

*Clinica Alemana Santiago, Santiago de Chile, Chile; and�Pontificia Universidad Catolica, Santiago de Chile, Chile

Purpose: AEERPS is a rare and catastrophic epileptic encephalopathyreported in 1986. Its etiology is still under study, immunological disorderis postulated due to the presence of autoantibody to glutamate receptorGlue2. This study presents 3 Chilean cases that meet defined clinical cri-terions (SAKUMA).

Method: A retrospective report of three cases displaying these clinicalcriterions: prolonged acute phase, partial seizures with symptoms persist-ing from the acute to the convalescence phase, seizures frequently evolv-ing into epileptic status, marked intractability of seizures, and exclusionof related disorders. All cases were studied using continuous and inter-mittent electroencephalography and several MRIs. The follow up periodfor clinical outcome was an average of 2 years.

Result: Three cases, 2 females, 33 months and 8 years old, and a male,36 months, with 5, 14, and 3 day fevers respectively. All had sudden

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conscience impairment and generalized tonic clonic seizures evolving toa refractory convulsive state (CS). Treated with 11, 13, and 14 AED,IVGG, MPS. Normal MRIs at admission. EEG showed initial diffuseslow waves with focal or generalized spikes and burst-suppression pat-tern. Evolutions were refractory epilepsy, severe mental retardation,spastic quadriparesis, gastrostomy. Tracheostomy in both females. Allhad AcRc Glut epsilon 2 in CSF (+).

Conclusion: AERRPS evolves to refractory epilepsy from the actuephase, therefore CS could be the first step in an epileptic encephalopathy.It could have an auto-immune etiology, related to Ac receptor Glue2 inCSF. The prognosis is poor. More studies are necessary to understand thephysiopathology and establish effective treatment.

p528AUTOIMMUNE MEDIATED SEIZURES WITH ENCEPH-ALOPATHY: A REVIEW OF CLINICAL AND ELECTRO-PHYSIOLOGICAL FEATURESY. Hacohen*, S. Tang�, Y. A. Hernandez Vega�, S. Wright*,C. Hemingway�, A. Clarke§, E. Wassmer–, A. Vincent*, andM. Lim�

*University of Oxford, John Radcliffe Hospital, Oxford, UK;�Evelina Children's Hospital, London, UK; �Great OrmondStreet Hospital, London; §St Georges Hospital, London; and–Birmingham Children¢s Hospital, Birmingham,

Purpose: To describe the seizure semiology and electrophysiologicalfeatures of paediatric patients with presumed autoimmune epilepticencephalopathy.

Method: Patients (n=40) presenting with a new onset seizure disorderand encephalopathy who were subsequently diagnosed with an autoim-mune aetiology were identified from 5 tertiary paediatric neurology cen-tres (2007–2010). Clinical and investigative data (including EEG) wereretrospectively reviewed.

Result: Generalised seizures (generalised tonic-clonic, atypicalabsence, atonic) were the most common (n=34), followed by focal dys-cognitive seizures in 18 cases. Focal seizures were reported in 9, with epi-lepsia partialis continua seen in 2 cases. Seizures were resistant to firstline therapy leading to intensive care support in 13 (32%).

EEG was performed in 39 cases. Initial EEG was encephalopathic orshowed a slow background in 35 (90%). Ten of these cases had asymmet-rical slow wave activity. Of the remaining four, two (5%) demonstratedfast activity presumed secondary to drugs; one (3%) was normal; and one(3%) had focal epileptic discharges. Initial and/or subsequent EEGswhere performed demonstrated epileptiform discharges in 11, which wasmultifocal in five and focal in six (temporal/parietal n=3, anterior n=1,posterior n=1).

An auto-antibody was found in 45% of the patients (10 NMDAR, 7VGKC and 1 with Glycine receptor antibodies). There were no statisticaldifferences between the antibody positive and negative groups in the fre-quency and type of seizures witnessed.

Conclusion: Autoimmune epileptic encephalopathies have a heteroge-neous presentation with different type of seizures. Refractivity to antiepi-leptic treatment during the acute presentation appears to feature in thisgroup of patients.

p529THE CURRENT TREATMENT OF INFANTILE SPASMSAMONG MEMBERS OF THE CHILD NEUROLOGYSOCIETYS. M. Joshi*, J. R. Mytinger�, and P.E.R.C. Section On InfantileSpasms�

*University of Michigan, Ann Arbor, USA; �University ofVirginia, Charlottesville, VA, USA; and �Ann Arbor, USA

Purpose: Infantile spasms (IS) are age-specific seizures commonlyassociated with an epileptic encephalopathy. The optimal evaluation andtreatment of children with IS is not known. The aim of this survey was toassess the current approach to IS and to plan future multicenter clinicaltrials.

Method: A survey was distributed electronically to members of theChild Neurology Society. Anonymous responses were collected over atwo week period.

Result: The response rate was 18.5% with 222 responses. Ninety-fourpercent of responders were from the United States. Seventy percent ofresponders reported seeing 10 or fewer new-onset cases of IS per year.The most commonly used first-line treatments for IS due to an unknownetiology were adrenocorticotropic hormone (ACTH) (67%), oral corti-costeroids (15%), and vigabatrin (9%). The most commonly used first-line treatments for IS due to a structural/metabolic etiology (excludingtuberous sclerosis [TS]) were ACTH (44%), oral corticosteroids (23%),vigabatrin (14%), and topiramate (12%). Most responders (86%) use vig-abatrin as the first-line treatment for IS due to TS. We found that the diag-nostic evaluation of IS varied among clinicians.

Conclusion: While ACTH is still the most commonly used first-linetreatment for IS not due to TS, some clinicians use corticosteroids, vig-abatrin, and topiramate as first-line treatments for this group. The evalua-tion and treatment of IS varied among responders. Infantile spasms arerelatively uncommon, therefore future clinical trials will require multi-center collaboration. An important first step in such collaboration is thestandardization of the evaluation and treatment practices within andbetween participating centers.

p530REPETITIVE TRANSCRANIAL MAGNETIC STIMULA-TION CAN BE ADJUNCTIVE METOD TO LOW ANTI-CONVULSANTS DOSESV. Kistsen, and V. EvstigneevBelMAGE, Minsk, Belarus

Purpose: The aim of our study is to assess the effectiveness of low-fre-quency repetitive transcranial magnetic stimulation (rTMS) as an adjunc-tive treatment for epilepsy patients.

Method: Nineteen patients (mean age 35.4€2.9 years) who take sub-therapeutic doses of anticonvulsants (AED) were studied. RTMS (1Hz, 20% of big ring coil (Neurosoft) MMI intensity) was performedduring ten consecutive days at the temporal lobe projection. Some ofpatients had prolonged rTMS course - two times per week during 2monthes. The point of stimulation was selected by MRI and EEG data.The neuropsychological tests, QOLIE-31 and SSQ were performed forall patients.

Result: Mean seizure frequency per week after 10 rTMS significantlydecreased in the following 4-week after rTMS period compared withthe pre-treatment period (4.12 vs. 0.75; P=0.023) which correspondsto 76% reduction and correlated with topiramat taking. Number of in-terictal epileptiform discharges decreased in 62.5% patients (P<0.05).There were increasing of alpha-rhythm amplitude and frequency inall patients. Amplitude, index, number and size of pathologic slowEEG-activity focuses were lowered in 80% cases (P<0.05) during 4weeks period after rTMS. Improvement of neuropsychological tests,QOLIE-31 and SSQ results were revealed (P<0.05). Chronic rTMSsupported condition of seizure frequency decreasing and positiveEEG changes.

Conclusion: 1 Hz low intensity rTMS has a significant antiepilepticeffect in patients when combined with small doses of anticonvulsantswhat can to allow AEDs negative symptoms reduction. Additionally, ourresults indicate that rTMS can improve the psychological condition andquality of life of these patients.

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p531EFFECT OF PHYSICAL EXERCISE DURING ADOLES-CENCE ON BEHAVIORAL CHANGES IN RATS SUB-MITTED TO PILOCARPINE MODEL OF EPILEPSY INIMMATURE BRAINR. M. Arida*, F. G. Novaes*, S. Gomes Da Silva*, M. Toscano-Silva*, L. Peixinho-Pena*, F. Scorza�, and E. Cavalheiro�

*Universidade Federal de S¼o Paulo, S¼o Paulo, Brazil; and�UNIFESP, Sao Paulo, Brazil

Purpose: To investigate whether a physical exercise program under-taken during adolescence can influence behavioral changes of rats sub-mitted to status epilepticus (SE) in early life using the pilocarpine model.

Method: Male Wistar rats at 18 (P18) and 28 (P28) days old weredivided into four groups: control, exercise, SE and SE exercise (n= 12each group). SE was induced through the administration of pilocarpine(170 and 260 mg/kg, i.p., at P18 and P28 respectively). Animals fromP18 were subject to the exercise program between P21 and P90 and ani-mals from P28 between P31 and P90. Behavioral analysis to determinethe number of seizures was performed from P45 to P90. Open Field andMorris Water Maze tests (between P55 and P62) were performed for bothgroups.

Result: Only animals submitted to SE at P28 presented spontaneousrecurrent seizures during the observational period. A significant reduc-tion in seizure frequency was observed in comparing the SE exercisewith the SE group. In the Water Maze test, lower latency to find theplatform was detected in exercise group compared to control group(P18/P28). Nevertheless, no significant difference was observed amongSE and control groups and SE and SE exercise groups (P18/P28). Inthe Open field test, a significant difference was observed in centrallocomotion between exercise and control groups and SE exercise andSE (P18/P28).

Conclusion: Our findings indicate that physical exercise program dur-ing the adolescent period reduces seizure frequency and increases explor-atory locomotion in rats submitted to pilocarpine model in early life.

p532WHOLE VIBRATION THERAPY IN PERSONS WITHEPILEPSY AND ADDITIONAL HANDICAPS: A FEASI-BILITY STUDYI. Smolenaers, F. Tan, and F. SchouwenaarsKempenhaeghe, Sterksel, The Netherlands

Purpose: This feasibility study follows from a previous study (K. Beer-horst, F. Tan - 2009) on the prevalence of low bone mineral density(BMD) in adult residents of a tertiary epilepsy center. 78% of the researchpopulation (patients with epilepsy and additional handicaps) had a lowBMD: osteopenia (43%) or osteoporosis (35%). Pharmaceutical treat-ment was started by prescribing Bisphosphonates, vitamin D and/or Cal-cium. Because of the drawback of Bisphosphonates (no evidence howlong treatment should continue, possibility of side effects, precautionswhen swallowing the drugs) we looked for alternative therapies to posi-tively influence the BMD.

Method: After reviewing the literature and consulting experts, WholeBody Vibration (WBV) Therapy emerged as a possible therapy. WBVhas demonstrated modest effects in other populations. In collaborationwith the manufacturer the standard WBV settings were determined. Aftereach session of WBV training, a log and questionnaire is filled. Assess-ments are scheduled at fixed times.

Result: Twenty patients met the inclusion criteria. All were diagnosedwith epilepsy and an intellectual/physical disability. No patient withdrewafter the try-out, and all started treatment in January 2012, three times

weekly with the standard setting. The settings are gradually increased infrequency and duration according to individual possibilities.

Discussion: The preliminary results of this feasibility study show thatWBV is tolerated by patients with epilepsy and ID. More detailed data onacceptance and tolerability will be accumulated during the 12 month-per-iod of the study. Presumably, the group is too small and the follow-up tooshort to show statistic significant results on BMD.


p533LOCAL SPECIALISTS’ KNOWLEDGE OF PLANTSWITHIN BARGUNA DISTRICT OF BANGLADESH: ASAFE ALTERNATIVE THERAPY FOR EPILEPSY INPATIENTS WITH BRAIN INSUFFICIENCYM. A. H. MollikPractical Academy on Wise Education and ResearchFoundation, Dhaka, Bangladesh

Purpose: Epilepsy is prevalent worldwide and is also present in bothrural and urban areas of Bangladesh. Due to epidemiological transitionthe burden of this disorder is high. Patients along with their families andthe whole society suffer from a range of physical, psychological, andsocioeconomic problems. Allopathic medicines have no known remedyfor cure of epilepsy but merely serve to control secondary symptoms. Onthe other hand local specialists claim to treat of epilepsy with plantsresulting in complete cure. The studies were carried out in Barguna dis-trict of Bangladesh.

Method: Interviews were conducted in the native dialect, and plant sam-ples as pointed out by the local specialists in guided field-walks were col-lected, and identified at the Bangladesh National Herbarium. Localspecialists administered treatment mainly by the concoctions, decoctionsmajorly through oral and dermal routes to treat of epilepsy.

Result: The plant names obtained in the studies included Achyranthesaspera L., Aloe vera (L.) Burm.f., Bacopa monnieri (L.) Wettst., Cinna-momum camphora (L.) J.Presl, Cocos nucifera L., Datura metel L., Ficusbenghalensis L., Lawsonia inermis L., Maranta arundinacea L., Nigellasativa L., Ocimum gratissimum L., Santalum album L., and Stephaniajaponica (Thunb.) Miers.

Conclusion: Anti-epilepsy activities have been reported for a number ofplants in the scientific literature for the plants used in Bangladesh fortreatment of epilepsy. It is expected that the plants observed to be usedfor treatment of epilepsy by the local specialists can be subjected for fur-ther bio-activity studies, which studies can lead to discovery of betterdrugs.

p534SUCCESSFUL PLASMA EXCHANGE TREATMENT OFMULTIFOCAL MYOCLONUS. TWO CASE HISTORIESI. Gati*, O. Danielsson*, G. Leijon*, V. Szekeres�, N. Dizdar*,H. Gauffin*, and M. Vrethem**Linkçping University, Linkçping, Sweden; and �Division ofNeurology, P�cs, Hungary

Purpose: Four- and six-years follow up of two adult patients withacquired multifocal myoclonus are presented.

Method: Detailed case histories and clinical data are presented.

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Result: Myoclonic jerks in the head, upper extremities, and in theabdominal muscles were the dominating symptoms, together withexcessive sweating. Emotional or physical stress and exertion of mus-cle contraction triggered the symptoms. Repeated electroencephalogra-phy (EEG) and electromyography (EMG) did not demonstrate centralnervous system hyperactivity and peripheral muscle hyper excitability.Based on the clinical symptoms brain stem origin was assumed.Administration a several different antiepileptic drugs were ineffective.An autoimmune mechanism was postulated on the basis of a thresholdincrease of voltage-gated potassium channel antibodies. Monthly regu-lar intravenous immunoglobulin treatment resulted in one month symp-tom-free periods, during two years follow up in one patient, while theimmunoglobulin treatment had no effect in the other patient. Plasmaexchange caused marked recovery, in both cases. One patient gainedsix months symptom-free periods, after 5 consecutive plasmaexchanges, while the symptoms of the other patient were substantiallydecreased during a period of 4 - 5 months, after the treatment. None ofthe patients need antiepileptic therapy whilst on regular plasmaexchanges.

Conclusion: These case histories emphasise that immune-modulatingtreatment could be effective in central nervous system hyperactivity dis-orders, even if only weak laboratory data support the autoimmune mecha-nism. These treatments probably need to be aggressive, at least in thebeginning and continous over time, as earlier suggested by Angela Vin-cent and her co-workers.

p535WORSENING OF SEIZURES FOLLOWING ABRUPTDISCONTINUATION OF MARIJUANA IN AN EPILEPSYMONITORING UNITA. Kabir*, M. Hegde�, C. Santos-Sanchez�, C. Hess�, andP. Garcia�

*San Francisco VA Medical Center, San Francisco, CA, USA;and �University of California San Francisco, San Francisco,CA, USA

Purpose: Cannabinoids such as marijuana have been described to haveanticonvulsant properties. These findings however remain controversial.Two reports described a reduction in seizure frequency after marijuanause (Consroe 1975, Ellison 1990), while another suggested sporadic mar-ijuana caused seizures to recur after remission (Keeler 1967). Two dou-ble-blinded placebo-controlled studies used cannabidiol (CBD), theprimary non-psychoactive compound of cannabis, as an adjunct to anti-convulsants. Cunha et al (1980) demonstrated a beneficial effect in 7 of 8patients; while Ames and Cridland (1986) showed no significant changein seizure frequency for 12 patients.

Here, we describe two additional well substantiated patients, whodemonstrated significant benefit from chronic marijuana use.

Method: We reviewed our experience at UCSF and the SFVAMC withpatients undergoing continuous vEEG monitoring, who demonstratedincreased seizures in the setting of abrupt cannabis discontinuation.

Result: Following discontinuation of marijuana, while continuing theiroutpatient medication regimen, two patients suffered dramatic increasesin seizure frequency, suggesting that outpatient marijuana usage had con-tributed substantially to seizure control.

Conclusion: We present two cases of patients who derived benefit inseizure control from marijuana, demonstrated by worsening seizures inthe setting of abrupt marijuana withdrawal. These cases therefore suggestthat, for at least a subset of patients with focal epilepsy, marijuana usemay provide an anticonvulsant effect. Alternatively, our cases may repre-sent cannabis withdrawal, however this is unlikely given the lack of otherwithdrawal symptoms.

We believe that these cases support further research into the potentialbenefits of medicinal marijuana for patients with epilepsy.

p536THE KETOGENIC DIET IN CHILDREN WITH DRAVETSYNDROME - THE AUSTRIAN EXPERIENCEA. Dressler, M. Mçrzinger, E. Reithofer, P. Trimmel-Schwahofer, A. M�hlebner-Fahrngruber, G. Pahs, F. Benninger,R. Grassl, and M. FeuchtMedical University Vienna, Vienna, Austria

Purpose: Dravet syndrome is a rare epilepsy syndrome in infancy withmultiple seizure types, psychomotor slowing and unfavourable outcome.The ketogenic diet has proven some efficacy in Dravet syndrome, andhas shown to be efficacious in other seizure disorders on prolonged gen-eralised seizures and on fever induced status epilepticus. Our aim was toevaluate the efficacy and the safety of the ketogenic diet in patients withDravet syndrome.

Method: We analysed retrospectively data of all children with a clinicaland genetically verified diagnosis of Dravet syndrome at the MedicalUniversity of Vienna who were started on the ketogenic diet between1999 and 2012.

Result: We report on 8 children, 4 (50%) were responders. 1 childbecame seizure free, but relapsed because of incompliance adhering tothe diet. One responder relapsed after 3 months on the diet, whereas theother two responders (25%) are still on the diet with a persistent seizurereduction.

Conclusion: We observed a good initial response on the KD, but moder-ate long-term efficacy, probably due to the natural course of Dravet syn-drome. In contrast, 2 patients remained free from seizures underStiripentole. However, the KD prevented prolonged seizures and statusepilepticus, and no side effects with a need to interrupt the diet inresponders were observed.

p537CESSATION OF REFRACTORY CONVULSIVE STATUSEPILEPTICUS AFTER IMPLANTATION OF VAGUSNERVE STIMULATION (VNS) THERAPYA. Soto, G. Contreras, V. Sainz, and H. ScholtzCentro Medico Docente La Trinidad, Caracas, Venezuela

Purpose: To report a 4 year-old patient who showed cessation of refrac-tory convulsive status epilepticus (SE) after VNS implantation

Method: This patient had a previous history of perinatal asphyxia, hyp-oxic isquemic encephalopathy and seizures since the neonatal period.She was put on Phenitoyne (PHT) and Phenobarbital (PB). By the firstmonth of age, she had recurrent seizures appearing during sleep, openedthe eyes, stared with a tonic flexion of head. In November 2008 after aRotavirus Infection she had status epilepticus receiving diazepam andmidazolam. In January 2009, infantile spasms were observed with a typi-cal hypsarritmia pattern in the EEG. She also had focal and GTC seizures.She was admitted in the PICU receiving Pentothal and midazolam andreceived ACTH, LTG, TPM, Levetiracetam (LEV), CZP and a KetogenicDiet. In December 2009 she developed status epilepticus receiving mi-dazolam and Pentothal. Psychomotor deterioration was noted also. InMarch 2010 she had another status epilepticus and remained in a barbitu-ric coma for 20 days receiving Levetiracetam, Lacosamide, Vigabatrinand Clonazepan. She was implanted with VNS Therapy after the last epi-sode of refractory SE. Initial settings: OC 1.0 mA, frequency 30 Hz, PW500ls, ‘on time’ 30 sec, ‘off time’ 5 min.

Result: After VNS Therapy the patient had 100% reduction of convul-sive seizures. She has had 4 focal seizures not requiring admission toPICU. Her mental status has dramatically improved.

Conclusion: VNS Therapy may be a valid alternative for the treatmentof refractory convulsive SE in a specific group of patients.

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p538ELECTROLYTE HYDRATION THERAPY IN CONTROLOF SPIKE AND WAVE DISCHARGES IN THE WAG/RIJRAT MODEL OF ABSENCE EPILEPSYD. Isaev, A. Talnov, A. Savotchenko, and G. HolmesBogomoletz Institute of Physiology, Kyiv, Ukraine

Purpose: We hypothesized that hyperosmolarity may be responsible forthe antiseizure effect of electrolyte solution. In the present study, using aclassical animal model of absence epilepsy we attempted to extract theantiseizure effect of rice-based oral electrolyte solution due to hyperos-molarity from other possible effect of this electrolyte solution.

Method: Each rat was implanted with recording electrodes for thesubsequent EEG recordings. At the day of surgery rats were anesthe-tized with a mixture of ketamine/xylazine (80/8 mg/kg) intramuscu-larly. For recording animals were placed in a special chamber andspontaneous field potentials were recorded using multi-channel extra-cellular amplifier. The electrolyte solution contained: sodium chlorideof 3.4 g/L, potassium chloride 1.3 g/L, trisodium citrate, 2.9 g/l; rice-carbohydrate 40g/L; which provide per liter sodium 90 mEq, potas-sium 20 mEq, and a 270 mOsm. Spike and wave discharges (SWD)were counted manually by an investigator blinded to treatment groupfor per blocks of one hour.

Result: Analysis of EEG recordings showed a gradual decrease of num-ber of SWD per hour during the time of electrolyte solution consumption(33.0€2.9% of control level, p < 0.01). There were no changes in peakfrequency (7.2€0.4 Hz) and duration (6.4€1.5s) of SWD compare to con-trol recordings.

Conclusion: The present study shows that using electrolyte base therapycan be effective as add on therapy to treat absence epilepsy. Treatment ofrefractory absence seizures with rice-based formulas may provide a costeffective, efficacious treatment of absence seizures. Whether such dietarytreatment will carry over to other seizure types remains unclear.

p539TEMPORAL VERSUS FRONTAL LOBE SEIZURESWITH AUTOMATISMS IN CHILDREN WITH SURGI-CALLY VERIFIED EPILEPTOGENIC ZONEO. GrinenkoKazaryan Clinic of Epileptology and Neurology, Moscow,Russian Federation

Purpose: To compare semiology of seizures with automatisms originat-ing from the frontal lobe (FLS) and from the temporal lobe (TLS) in chil-dren who became seizure-free after surgery.

Method: We analyzed 25 videotaped TLS from ten patients and 16 vid-eotaped FLS from six patients aged 3.5–16 years (mean 7.9 years). Med-ian follow-up was 18 months (range 5–40 months). Fourteen types ofsymptoms and signs were evaluated in every seizure. The course of eachseizure conditionally was divided in three consecutive stages. The timeof symptoms onset was determined in relation to each stage of seizure.

Result: Ipsilateral distal hand automatisms with contralateral arm dis-tonic posture were seen only in the TLS (13 seizures in 5 patients),whereas proximal automatisms were more frequent in the FLS (14 sei-zures in 5 patients), then in TLS (5 seizures in 2 patients) (P <0.001).

Ipsilateral manipulating distal automatism were more common in theTLS (P <0.007) (15 seizures in 7 patients) as bimanual manipulating dis-tal automatism - in the FLS (9 seizures in 3 patients) (P <0.004).

Nonmanipulating rounded rhythmical proximal automatisms in TLSwere determined exclusively contralaterally and only during the firstthird of the seizure (5 seizures in 2 patients).

Oral automatisms in FLS were seen only in the last third of the seizure(6 seizures in 2 patients).

Conclusion: Automatisms in both TL and FL seizures have a differentand specific order of appearance and laterality. A distinctive and stronglycontralateral rhythmical rounded proximal automatism was identified inTLS

p540EFFECTIVENESS OF THE USE OF AN OMEGA 3/6COMBINATION IN PAEDIATRIC PATIENTS WITHREFRACTORY EPILEPSYE. J. Barrag�n P�rez*, R. Huerta Albarran�, and I. HerediaBarrag�n**Hospital Infantil de M�xico Federico G�mez, M�xico, DF,Mexico; and �Hospitasl General de M�xico, Mexico City,Mexico

Purpose: To compare efficacy and safety in the treatment of refractaryepilepsy with a supplement combining EPA, DHA (omega 3 fatty acids)and GLA (Omega 6).

Method: We review patients from the neurology department of the Chil-dren¢s Hospital of Mexico who have refractory epilepsy, evaluating clini-cal characteristics of seizures, number of seizures and antiepileptic drigs(AED) 792 mg of EPA, DHA and GLA were administred for four weeksin order to assess the frequency of seizures as well as tolerbility and prob-able side effects.

Result: The studywas condcuted with a total of 19 patients with followup four weeks after the start of supplementation. we obtain a satisfactoryclinical response with >80% decrease in daily number of seizures in morethan 60% of patients. The mean number of seizures over all patients wasreduced significantly from 26–61 */- 37.5 to 5.92 € 3.48. In addition, asignificant improvement in the neurocognitive capacity was observed inall patients.

Conclusion: The co-adjuvant supplementation with high doses of EPA/DHA/GLA may result in a reduction of the number of seizures in refrac-tary epilepsy having in addition significant impact on neurocognitiveaspects. To enhance the quality of life for paediatric patients with epi-lepsy supplementarion with a specific combination of these omegasshould be reconsidered.

p541EFFECTS OF VAGUS NERVE STIMULATION ON SEI-ZURES AND CARDIOVASCULAR RESPONSES INPATIENTS WITH DRUG-RESISTANT EPILEPSYI. Naldi*, B. Mostacci�, M. Broli*, P. Guaraldi*, L. Alvisi*,G. Barletta*, F. Pittau*, C. Leta*, F. Bisulli*, P. Cortelli*, andP. Tinuper**IRCCS Istituto delle Scienze Neurologiche, Bologna, Italy; and�IRCCS Istituto delle Scienze Neurologiche di Bologna,Universit di Bologna, Bologna, Italy

Purpose: We aimed to describe the impact of vagus nerve stimulation(VNS) on seizure frequency and cardiovascular responses in refractoryepilepsy patients.

Method: Among refractory epilepsy patients who underwent implanta-tion of VNS, from February 2007 to November 2011, we selected caseswith a follow-up at least of one year. Neurological examination, brainmagnetic resonance imaging, video-polygraphic recording includingEEG and EKG, cardiologic examination, echocardiography, Holter EKGand ambulatory polysomnography were performed in all patients beforeVNS implantation. All patients underwent Head-up Tilt Test (HUTT),Valsalva Maneuver (VM), Hand-Grip (HG), Deep Breathing (DB) andCold-Face (CF) before and after implantation.

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Result: Ten patients were included, mean age was 41.9 years (range 28–55), mean disease duration was 32.9 years (range 20–55). All patientshad refractory focal seizures with or without secondary generalization.Seizure frequency improved from 30% to 90% in 6 patients, did notchange in 3 patients, worsened in 1 patient and the VNS had to be turnedoff. There was no significant change in HUTT, VM or DB after VNS.The increase in Systolic blood pressure during CF and HG was signifi-cantly higher post VNS (respectively n=8, p=0.042; n=7, p=0.032 com-pared to pre VNS implantation.

Conclusion: Seizure frequency improved in 6 out of 10 patients withVNS therapy. Our results show that VNS does not impair autonomic car-diovascular regulation, but increase sympathetic vasoconstrictorresponses to pressor stimuli.

p542HAS TRANSCRANIAL DC STIMULATION PRO-LONGED AFTER EFFECTS ON ABSENCES?M. Zobeiri*, A. Luttjohann�, and G. Van Luijtelaar�

*Donders Institute for Brain Cognition and Behaviour, RadboudUniversity Nijmegen, Nijmegen, The Netherlands; and�Radboud University Nijmegen, Nijmegen, The Netherlands

Purpose: Transcranial direct current stimulation (tDCS) is a putativenovel non invasive therapy which might be beneficial in cortical epilep-sies. It is widely accepted that the for absence epilepsy typical SWDshave a cortical origin. Here it is investigated whether anodal and cathodaltDCS affects local cortical excitability in a genetic rodent model ofabsence epilepsy and whether the effects persisted the next day.

Method: Ten male WAG/Rij rats, minimally six months of age wereused. Two stimulation electrodes were cemented on the cranium abovethe focal regions bilaterally, EEG electrodes were epidurally implanted.Rats received 4 series of 15 minute cathodal and anodal stimulation of100 lA with an interval of 1h45 in a counter-balanced order while EEGwas recorded. In a second experiment (n=4) the cumulative effects ofcathodal stimulation with the same intensity and duration at 4 differenttime points were examined and compared with baseline and post stimu-lation day.

Result: Cathodal tDCS decreased the number and total duration ofSWDs in comparison with anodal stimulation, but only during and afterthe first 15 min of stimulation (Exp 1). The effects of cumulative cathodaltDCS (Exp 2) tended to increase (F= 3.14, p=0.06) over time. Rats hadless SWDs in the post stimulation day compared to base-line. Histologi-cal evaluation showed no abnormalities in the stimulated regions.

Conclusion: The preliminary outcome shows that cathodal tDCS canbe considered as an effective method to reduce SWDs in this geneticabsence model and that its effects may outlast the actual stimulationperiod.


p543OPTIMIZED INDIVIDUAL TREATMENT PROTOCOLSIN PATIENTS WITH DRAVET-SYNDROME USINGELECTRONIC DOCUMENTATION WITH EPIVISTA�R. Boor*, C. Dreiwes*, and U. Stephani�

*Northern German Epilepsy Centre, Schwentinental, Germany;and �University Medical Center Schleswig-Holstein, Kiel,Germany

Purpose: Can we improve seizure control and optimize individual treat-ment protocols in patients with Dravet-S using electronic documenta-tion? What are useful anticonvulsant (ACD) combinations? Is Stiripentol(STP) combined with Clobazame (CLB) clinically useful.

Method: 14 patients with Dravet syndrome aged 3–28 (median 11.5)years have been continuously seen in our epilepsy centre since 2007. Theelectronically documented clinical course in EpiVista� was used to opti-mize the anticonvulsant (ACD) combinations in each patient. Pharmaco-resistant patients received STP+CLB after 3–11 (median 8) ACD, and wecompared the seizures during 2 months baseline (BL) before STP intro-duction with the 2 months observational period (STP maintenance dose,> 0.1 mg/kg CLB).

Result: 4/14 patients became seizure free with VPA+TPM (n=3) orVPA+TPM+Br- (n=1). There was one dropout (loss of follow up). Theremaining 9 patients recieved STP (12–29 mg/kg, median 19) + CLB(0.10–0.16 mg/kg median 0.12). Seizure reduction > 50% occurred in 5/9patients and one additional patient had been free of seizures since 9months at the last visit with VPA+TPM+STP+CLB.

Conclusion: Electronically augmented titration of ACD provides goodseizure outcome in Dravet-S. The combination of STP+CLB is helpful inpharmacoresistant Dravet–S.

p544REFRACTORY EPILEPTIC ENCEPHALOPATHYRELATED TO MYCOPLASMA PNEUMONIAE INFEC-TIONR. Buenache*, P. Morillo�, M. A. Meseguer*, C. PerezCaballero�, P. Quintana*, and G. Lorenzo§

*Hospital Ramon y Cajal., Madrid, Spain; �Ramon y CajalUniversity Hospital, Madrid, Spain; �Ram�n y Cajal Hospital,Madrid, Spain; and §Paediatric Neurology, Ramon y CajalUniversity Hospital, Madrid, Spain

Purpose: To report a case of a girl with febrile infection–related epi-lepsy syndrome (FIRES) after Mycoplasma infection, and successfulresponse to sequential plasmapheresis.

Method: We report the case of a previously healthy 4-year-old girlwho initially presented decreased level of consciousness, fever up to39�C and recurrent partial and generalized seizures. Blood tests andCSF were normal. Slow background EEG activity. She was diag-nosed with encephalitis. Broad-spectrum antibiotics and acyclovirwere initiated.

Result: All microbiological research including serologies, PCRs andcultures to search for neurotropic agents resulted negative, except forMycoplasma pneumoniae seroconversion. During her evolution shedeveloped refractory and recurrent clinical and electrical status epilepti-cus without response to valproate, phenytoin, levetiracetam, midazolam,propofol and thiopental. The neurometabolic study (blood, urine andCSF) was normal. Antineuronal antibodies and other autoimmune studieswere negative. Normal brain MRI. EEG showed slow spike and wave dis-charges in both hemispheres. Immunology of CSF: initial elevated IgMand IgG in CSF. After high-dose steroids treatment, decreased Ig CSFlevels, with later persistence of high levels; therefore she was treated withimmunoglobulin and several multiple sessions of plasmapheresis. After-wards, she recovered with a residual seizure disorder and autism-likebehaviour. Control brain MRI showed cortical atrophy. Two monthslater, she remains without seizures, treated with clobazam, ethosuximide,valproate and zonisamide.

Conclusion: Our case supports the hypothesis that Mycoplasma infec-tion may trigger a FIRES. Furthermore, an adequate immunomodula-tory therapy should be effective when an immunological disorder isobserved.

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p545DESCRIPTION OF CLINICAL CASE OF FEBRILEINFECTION-RELATED EPILEPSY SYNDROME (FIRES)S. N. Sivkova*, E. I. Bogdanov�, F. M. Zaykova*, andE. A. Morozova**Children Municipal Hospital, No. 8, Kazan, RussianFederation; and �Kazan State Medical University, Kazan,Russian Federation

Purpose: Febrile infection-related epilepsy syndrome (FIRES) is asevere condition occurring mainly in children, with acute onset of statusepilepticus during a febrile illness and subsequent refractory epilepsy inpatient with previous normal development. Sometimes it causes difficul-tes for diagnostic at the onset.

Methods: We prospectively identified FIRES in 7-year-old boy, whohas refractory symptomatical focal epilepsy and progressive cognitiveand behavioral disturbances, despite antiepileptic treatment.

Results: 7-year-old boy had febrile respiratory infection for 6 days. At 7day acute symptoms had appeared: psychiatric and cognitive problems(agitation, acute memory and disorientation, psychosis, speech and psy-chomotor arrest); neurological – left hemiparesis, meningeal signs. Focalautomotor seizures with secondary generalization had been started about20–25 times a day. All laboratory analyses (blood, cerebrospinal fluid),virul test, immunological test and MRI were normal. EEG showed multi-regional epileptiform activity. The boy was treated like an atipical viralmeningoencephalitis, but it was unsuccessful. Only using prednisolon 30mg/day with gradual reduction of a doze and some combinations of an-tiepileptic drugs (oxcarbamazepine – 38 mg/kg/day, valproic acid 45 mg/kg/day, topiramate 7.5 mg/kg/day) have decreased frequency of seizures.One year later patient continued to present clusters of focal seizures andprogressive cognitive regression.

Conclusion: This description has shown that we always should keep inmind the possibility of development of severe epileptic encephalopathyin children after febrile infection with frequent seizures.

p546CLINICAL PROFILE AND TREATMENT OUTCOME INFEBRILE INFECTION–RELATED EPILEPSY SYN-DROME (FIRES) IN SOUTH INDIAN CHILDRENV. Kollencheri Puthenveettil, S. Patil, A. G. Roy, D. Dhami,C. Nidheesh, and A. KumarAmrita Institute of Medical Sciences, Cochin, India

Purpose: To describe clinical features and outcome of febrile infectionrelated epilepsy syndrome (FIRES) in South Indian children.

Method: Previously normal children aged between 2 to 12 years admit-ted with a prolonged status epilepticus or encephalopathy with recurrentseizures following a non-specific febrile illness between January 2009and July 2011 were included.

Result: A total 17 children were identified. 4 children were excludedbefore final analysis. Age ranged between 2–12 years (median 6 year3 month). Seizure onset was 1–14 days (median 5 days) after thefever. Nonspecific respiratory infection was recorded in 10 children.Ten patients had status epilepticus at presentation. Four had recurrentseizures with encephalopathy. Cerebrospinal fluid studies were nor-mal in all. Interictal EEG showed generalized slowing in all children.Focal epileptiform abnormalities were seen in 9. Neuroimaging wasnormal in 10 children (9 MRI, 1 CT). Treatment included multipleantiepileptic drugs (4–7 AED; median 5 drugs). Barbiturate comawas used in 6 for 2 to 10 days (median 2 days). Steroids were usedin 10 (76.92%) children and IVIG in 4 (30.76%). Two children died

in the acute phase and 8 developed drug resistant epilepsies (61.5%).Eight children had severe cognitive disturbance (61.5%). Only 2 chil-dren recovered without significant sequelae, both of them receivedIVIG in acute phase.

Conclusion: This is the largest clinical series of FIRES from India.Treatment outcome remains poor despite using multiple AEDs, immuno-therapy and barbiturate anesthesia. Immunotherapy with IVIG duringearly phase of the illness may have a favorable outcome.

p547CONCORDANCE BETWEEN HISTORY AND EPILEPSYMONITORING UNIT EVALUATION FOR DIAGNOSINGSEIZURESE. Khalid, S. Sinha, and K. A. SiddiquiNational Neurosciences Institute, King Fahad Medical City,Riyadh, Saudi Arabia

Purpose: History and examination (H&E) are of a paramount impor-tance in the diagnosis of epilepsy. Accurate history can help selectpatients who require comprehensive Epilepsy Monitoring Unit (EMU)evaluations i.e: long term EEG monitoring, dedicated structural and func-tional neuroimaging and neuropsychological evaluation. A detailed his-tory could help us delineate seizure subtype and may obviate the need forcomprehensive evaluation, and be cost effective. We compared epilepsydiagnosis made in outpatients using historical information to comprehen-sive EMU evaluation.

Method: We reviewed seizure/spell diagnosis on consecutive patientsmade on basis of H&E and compared to the final diagnosis followingcomprehensive EMU evaluation. We also looked at their demographicsand mean duration of epilepsy.

Result: Ninety Six patients (Male-51, Female-45) with mean (+ SD) age24 (+10.1) years and duration of epilepsy 11 (+9.7) years were recruited.Following outpatient evaluation probable diagnosis of focal seizure wasmade in 37, generalised in 29, Paroxysmal Non Epileptiform Seizures(PNES) in 6, and evaluation was inconclusive for seizure type in 24patients. Following EMU evaluation diagnosis of focal epilepsy wasmade in 61, generalized epilepsy in 26, and PNES in 10 patients. Outpa-tient diagnosis was concordant to comprehensive EMU evaluation in44.8% (43/96), which was 44.3% (27/61) for focal seizure, 42.3% (11/26) for generalised and 50% (5/10) for PNES.

Conclusion: Concordance was seen in less then half of the patientsrecruited and was similar for all seizure subtypes. This study highlightsdeficiency of accurate history probably related to language barrier and orlack of health and educational literacy and signifies the importance ofEMU evaluation in our population.

p548SECONDARILY GENERALIZED SEIZURES IN TEMPO-RAL LOBE EPILEPSYB. B�n�*, A. Fogarasi�, R. Schulz�, C. Gyimesi*, Z. Kalm�r*,N. Kov�cs*, A. Ebner�, and J. Janszky**University of P�cs, P�cs, Hungary; �Bethesda Children'sHospital, Budapest, Hungary; and �Epilepsiezentrum Bethel,Bielefeld, Germany

Purpose: Secondarily generalized tonic-clonic seizure (SGTCS) mayrarely occur in temporal lobe epilepsy (TLE), but SGTCS is the majorrisk factor for sudden death and for seizure-related fatal injuries. Our aimwas to investigate clinical factors associated with the occurrence ofSGTCS in TLE by addressing two questions: (i) What clinical features

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differentiate TLE patients who regularly had SGTCS from those who didnot? (ii) Is there an association of secondarily generalized seizures withpreceding seizure elements and clinical data.

Method: We included 171 TLE patients (mean age: 34.4€10) who par-ticipated in our presurgical evaluation program, which included continu-ous video-EEG and MRI. Patients had a temporal lobectomy as a resultof mesial or neocortical TLE. To re-evaluate the archived seizures, weselected the consecutively recorded seizures of each patient. If the patienthad more than three recorded seizures, then we re-evaluated only the firstthree ones. Altogether 402 patients’ videorecorded seizures were re-ana-lyzed.

Result: A positive association between the presence of hippocampalsclerosis on the MRI and SGTCS in the patient history was found,while ictal speech and pedal automatism showed a negative associa-tion with a SGTCS history. The age of patients showed a positive,while patient's reactivity before and during the seizure, oral/pedalautomatisms, and vocalizations showed a negative association withsecondary generalization of a focal-onset seizure during video-EEGmonitoring.

Conclusion: Clinical features associated with SGTCS may help clini-cians during presurgical monitoring indentify high-risk patients forSGTCS. Our study may help in understanding the pathophysiology ofsecondary generalization.

p549THE SPECTRUM OF FRONTAL SEIZURES: ANATO-MO-ELECTRO-CLINICAL CORRELATIONS USINGSEEGA. Mcgonigal, F. Bonini, A. Tr�buchon-Da Fonseca,F. Bartolomei, M. Gavaret, and P. ChauvelService de Neurophysiologie Clinique & Institut deNeurosciences des Syst�mes-INSERM UMR 1106, Marseille,France

Purpose: To study whether patients with frontal lobe epilepsy may becategorised semiologically and whether certain semiological patterns areassociated with different sublobar seizure organisation.

Method: We studied anatomo-clinico-electrical correlations in 54patients with frontal lobe seizures, explored with stereoelectroencepha-lography (SEEG). Semiological features and SEEG data were identifiedand categorised in a semi-quantitative way. Hierarchical cluster analysiswas used to compare patients.

Result: Three main groups were characterised by a significant degree ofshared semiological features between patients. These showed distinctelectro-anatomical seizure organisation along caudo-rostral, mesio-lat-eral and dorso-ventral axes. Group 1 was characterised by elementarymotor signs (e.g. tonic posturing, head version, clonic jerks) withoutmore complex gestural motor behaviour, involving precentral and/or pre-motor structures. Group 2 was characterised by both specific elementarymotor signs and gestural motor behaviour with a non-naturalistic (‘‘non-integrated’’) appearance, involving both premotor and prefrontal struc-tures. Group 3 showed naturalistic (‘‘integrated’’) gestural motor behav-iour without elementary motor signs, arising from prefrontal structures.Emotional features were associated with mesial prefrontal involvement.Stereotyped movements were associated with dorsolateral prefrontal cor-tex involvement.

Conclusion: Categorisation of frontal seizures is possible according tosemiological features, corresponding to different electro-anatomicalorganisation along rostro-caudal, mesio-lateral and dorsoventral axes.Electroclinical reproducibility of seizures, within an anatomo-functionalframework, suggests an important role for cortico-subcortical circuits inseizure organisation.

p550IS THERE CLINICAL EVIDENCE FOR DIFFERENCESRELATED TO THE NEW CLASSIFICATION OF TEM-PORAL LOBE CORTICAL DYSPLASIA?S. Fauser*, C. Essang*, D. Altenm�ller*, A. M. Staack�,K. Strobl�, B. J. Steinhoff�, T. Bast�, S. Schubert-Bast�,M. Prinz*, J. Zentner*, and A. Schulze-Bonhage**Freiburg, Germany; �Kork, Germany; and �Heidelberg, Germany

Purpose: The new ILAE classification for focal cortical dysplasia dif-ferentiates between isolated FCD (FCD type 1) and with an associatedhippocampal sclerosis (FCD type 3a). The rational for this differentiationwas a presumed different clinical course.

Method: 50 patients with temporal FCD type 3a and 31 patients withtemporal FCD type 1 were included. Both patient groups were comparedto 18 patients with temporal FCD type 2.

Result: Patients with FCD type 1 and type 3a presented with similarclinical features. No differences were found with respect to age at epi-lepsy onset, age at epilepsy surgery, and the occurrence of an aura(mainly epigastric). A normal appearing lateral temporal lobe was seen in12% of patients with FCD type 1 and in 27% of patients with FCD type 3(p= 0.09). The postoperative outcome was nearly identical with 50–60%of patients completely seizure-free. Only febrile seizures were signifi-cantly more frequently reported in patients with FCD type 3a (p=0.03).FCD type 2, however, was clinically different with respect to the occur-rence and the type of auras [significantly less common in FCD type 2(p=0.02) and more polymorphic].

Conclusion: Patients with FCD type 1 and type 3a present with clinicallysimilar features, probably because of involvement of similar networksinto epileptogenesis. Based on these findings a splitting of temporal FCDinto FCD type 1 and type 3a founded on different clinical phenotypes ischallengeable. FCD type 2, however, presents with some peculiaritieswhich have not been considered in the ILAE classification so far.

p551EPILEPSY AND SPEECH-RELATED PROTEIN SRPX2CONTROLS NEURONAL MIGRATION IN THE DEVEL-OPING RAT BRAIN CORTEXM. Salmi*, N. Bruneau*, J. Cillario*, N. Lozovaya*, E. Buhler*,F. Watrin*, A. Massacrier*, T. Tsintsadze*, V. Tsintsadze*,C. Zimmer�, R. Cloarec*, C. Cardoso*, C. Villard�,F. Muscatelli*, P. Durbec�, V. Pauly§, I. Khalilov*, Y. Ben Ari*,N. Burnashev*, A. Represa*, and P. Szepetowski**INSERM U901 - INMED, Marseille, France; �CNRSUMR6216, Marseille, France; �INSERM U911, Marseille,France; and §AP-HM, Marseille, France

Purpose: Early developmental alterations of the human brain cortexcause severe brain malformations and are increasingly recognized as animportant determinant for a wide variety of common pathologies such asautism, dyslexia, epilepsy, or speech disorders. Mutations in sushi-repeatcontaining protein SRPX2 cause Rolandic epileptic seizures, either withspeech impairment (verbal dyspraxia) or in the context of abnormal gyra-tion of the speech cortex (perisylvian polymicrogyria). The participationof Srpx2 in the development of the rat brain cortex and the pathophysio-logical mechanisms associated with the disease-causing mutations wereinvestigated.

Method: In utero silencing of rat Srpx2 in the developing cortex wasobtained by electroporation of specific shRNA constructs at embryonicday 15, and was followed by the appropriate analyzes at the molecular,cellular, morphological, behavioral and electrophysiological levels.

Result: In utero silencing of rat Srpx2 in the developing cortex led toimpaired radial migration of projection neurons and was associated with

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increased post-natal susceptibility to epileptic seizures. Wild-type ratSrpx2 or human SRPX2, but not the mutant, human pathogenic proteins,rescued the cortical phenotype. Misplaced neurons showed morphologi-cal anomalies in vivo and silenced neurons displayed altered migrationex vivo. How Srpx2 interferes with cell migration at the molecular level,and the post-natal electrophysiological consequences of the in uteroSrpx2 silencing, are currently being investigated.

Conclusion: Overall our study demonstrates that Srpx2 controls neuro-nal migration in the developing rat brain cortex, and strongly suggeststhat altered neuronal migration participates in epileptic disorders of thespeech cortex including Rolandic epilepsy with verbal dyspraxia, andperisylvian polymicrogyria.

p552IGE OF LATE ONSET VERSUS IGE OF ‘‘CLASSICALONSET’’A. Valavanis, M. Spilioti, G. Zafeiridou, A. Safouris, T. Gatsios,A. Chatziapostolou, and A. KarlovasitouMedical School, Aristotle University, Thessaloniki, Greece

Purpose: Idiopathic generalized epilepsies (IGEs) are age-related epi-leptic syndromes mainly starting in childhood or adolescence and areconsidered to be rare after the second decade of life. The aim of this studyis to compare two groups of patients with IGEs, those with the classicalonset and those with the late one.

Method: Patients with IGE, treated at the outpatient epilepsy clinic(Medical School, Aristotle University, Greece) were retrospectivelyscreened. Population was stratified into two groups: 118 patients with sei-zure onset at <20 years (classical IGE) and 28 patients with onset at ‡20year (late onset IGE). The inclusion criteria were: unequivocal diagnosisof IGE and normal brain imaging. Demographic data, seizure types, epi-leptic syndromes, neuroimaging and EEG findings were also analyzed.

Result: A total of 146 Patients (mean age at seizure onset 17.8 years,range 8–56, SD 7.24) with IGE were identified: juvenile absence epilepsy(n:4, range 10–16, SD 2.8), juvenile myoclonic epilepsy (n:89, range 8–56, SD6.5) and epilepsy with generalised tonic-clonic seizures only(n:53, range 10–55, SD 8.39). The distribution of epilepsy syndrome withgeneralized tonic-clonic seizures (GTCSs) only, differ significantly in agroup comparison (p< 0.05). The other clinical and EEG parameters didnot differ throughout the groups.

Conclusion: The generalized epileptic syndrome with GTCSs only, wassignificantly higher in the group of late onset patients, but no other differ-ences of electroclinical features were found between the two age relatedgroups. Our study cannot confirm that IGE of late onset might be a sepa-rate nosological entity.


p553NATURAL PROGNOSIS OF EEG ABNORMALITIESAND INTELLECTUAL FUNCTIONS IN CHILDRENWITH ADHD AND/OR LDD. Turkdogan, and S. ZaimogluMarmara University, Istanbul, Turkey

Purpose: We aimed to study evolution of EEG abnormalities in childrenwith ADHD and/or LD.

Method: In 30 (aged 7–14, mean: 8.2€1.9 years, 7% female) patientswith ADHD and/or LD and an abnormal EEG, serial EEG examinationswere done in an interval of 3 to 42 months. Comprehensive battery of

cognitive tests assessing Full Scale Intelligence Quotient-FSIQ, attentionand executive functions (Wisconsin Card Sorting Test; Visual MemorySpan, subtest of Wechsler Memory Scale-Revised; Stroop Task; CategoryFluency) and verbal learning and memory functions (California VerbalLearning Test) were done in all patients within 2 weeks of EEG recordings.

Result: The initial EEG demonstrated epileptiform abnormalities in 26,focal slowing in 1 and both in 3 patients. The localization of abnormalitywas frontal in 10, centro-temporal in 9, occipital in 4, central in 2, tempo-ral in 1, parietal in 1, and generalized in 3 patients. Epileptiform poten-tials were activated by sleep in 12 patients. Epileptiform activity wasfrequent in 13, moderate in 2 and rare in 14 patients. The characteristicsof EEG abnormality persisted in consecutive recordings of 15 patientsafter 9 to 24 (mean: 15.4€4.7) months. Initial EEG abnormality (focal in13 patients and generalized in 1 patient) normalized after 3 to 42 (mean14.1€9.9) months. Comparison of consecutive intellectual functioningparameters in patients with persisting epileptiform potentials and patientswith normalized EEG did not demonstrate a significant change.

Conclusion: The intellectual functions in patients with ADHD and/orLD seems not to be affected by the presence of EEG abnormalities.

p554THE CLINICAL VALUE OF THE INCOMPLETE HIPPO-CAMPAL INVERSION IN EPILEPTIC AND NONEPI-LEPTIC PATIENTSE. Sasso*, E. Bortone*, I. Florindo*, D. Cerasti�, and G. Crisi�

*Neurology Unit, Parma, Italy; �Neuro-Radiology Unit, Parma,Italy

Purpose: Isolated incomplete inversion of the hippocampus (IIHH), asdefected fetal development, has been described in epileptic and morerarely in non epileptic subjects. We investigated the clinical features of apatient cohort presenting this morphologic variation and no other devel-opmental abnormalities at MRI.

Method: 34 consecutive patients with evidence of IIHH at 3T-MRI per-formed with ‘‘epilepsy protocol’’ have been included in the study. Typeand course of epilepsy, standard EEG, responsiveness to AEDs, neuro-psychological assessment, IIHI side have been collected for each subject.

Result: Median age of patients (M= 14; F= 20) was 41 yrs and medianepilepsy onset was 12 yrs. Only 6 out of 34 had no diagnosis of epilepsy.In the epileptic cohort partial seizures were more commonly reported(82%) with or without secondary generalization. Febrile convulsions ear-lier in life have been described in 4/28 cases. 8/28 had refractory epilepsywhereas the remaining 20 were at time satisfactorily controlled. 33 out of34 patients presented a left-sided IIHH. Side correlation between EEGand IIHH was impressively higher (85%) than in previous studies withregard to epilepsy cohort. Minor to mild cognitive impairment has beenobserved in only 3 subjects. Hippocampal morphometric investigationsleading to estimate the different involvement of hippocampal regions(head, body, cauda) are still in progress.

Conclusion: IIHH is a discrete hippocampal malformation often leadingto epilepsy. Present study confirms that non epileptic subjects are rareand that left-sided IIHH and EEG adherence can help to calibrate the epi-leptogenicity risk and maybe refractory sources.

p555PREDICTORS OF NEURODEVELOPMENTAL OUT-COME FOLLOWING EPILEPSY ONSET IN INFANCYH. O’Reilly*, K. Verhaert�, C. M. Eltze�, H. Cross�, R. Scott*,and M. De Haan**University College London, London, UK; and �Great OrmondStreet Hospital for Children NHS Trust, London, UK

Purpose: Infant onset epilepsy is associated with poor neurodevelop-mental outcome. Determining predictors of outcome is important in iden-

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tifying those children most at risk for developmental compromise. Theaim of this prospective population-based study was to identify neurologi-cal predictors of cognitive outcome in children at 3–5 years of age withepilepsy onset < 2 years.

Method: Children < 2 years of age presenting with recurrent unpro-voked seizures from a defined area of North London were enrolled overtwo years. Clinical assessments and neurodevelopmental evaluation wereperformed at enrolment using Bayley Scales of Infant and Toddler Devel-opment-III and at follow-up using the Leiter-R. Multiple regression anal-ysis was used to establish the relationship between individual clinical andinvestigative results and later cognitive outcome.

Result: Data from baseline and 3 year follow-up were available for 40children (25 male, age onset M=6.7months, age follow-up M=48.8months). At follow-up 55% had an IQ > 2SD below the mean. Lack ofseizure control, abnormal EEG and cognitive score at baseline accountedfor 78.8% of variation in IQ/cognitive scores (R =0.888, R2 =0.788).

Conclusion: 55% of the children with infant onset epilepsy were devel-opmentally delayed at 3-year follow-up. Abnormal EEG, cognitive scoreat presentation and lack of seizure control predicted function at followup. These findings suggest that children who are performing poorly atbaseline continue to display delayed development at follow-up and thisdelay is related to continuing seizure activity.

p556DEVELOPMENT AND BEHAVIOR OF CHILDRENAGED 2 TO 5 YEARS AFTER EXPOSURE TO ANTIEPI-LEPTIC MONOTHERAPY IN UTERON. Cossa, H. Garlipp, R. Kretz, A. Lçscher, P. Senf,B. Wandschneider, and B. SchmitzVivantes Humboldt Klinikum, Berlin, Germany

Purpose: Within GRAP (German Registry of Antiepileptic Drugs inPregnancy, which is associated with the EURAP-Project) we have con-ducted a questionnaire study focusing on the development between the2nd and 5th year of life.

Method: Participants were 346 mothers whose children were between 2and 5 years. Inclusion period was 2007–2010. For this analysis weselected 248 children exposed to one of the three most common mono-therapies: valproate (VPA, N = 51), lamotrigine (LTG, N= 140) or cab-amazepine (CBZ, N = 57). Mothers completed standardizedquestionnaires of child development (MCDI = Minnesota Child Develop-ment Inventory) and mental disorders in childhood (CBCL = ChildBehavior Checklist) annually.

Result: Significant differences were found for two subscales of theCBCL at age 2. VPA exposed children had higher scores in the emotionalreactive category compared to LTG exposed children (U = 46, r =-0.38, p< 0.017) as well as higher scores for the variable attention problems com-pared to the CBZ group (U = 7, r =-0.40, p < 0.017). There were no differ-ences at age 3, 4 and 5.

Conclusion: The results confirm VPA associated developmental prob-lems in children exposed to VPA in utero. These differences were onlyfound at the young age of two years. The investigation group was smalland selection bias cannot be ruled out. However, our results suggest thatdevelopmental problems may disappear with age.

p557MOTOR IMPAIRMENT DURING THE FORMATION OFBENIGN EPILEPTIFORM DISCHARGES OF CHILD-HOOD. TRUE OR FALSE?D. Zaytsev, L. Eletskova, D. Lutin, and N. TitovZaytsev's Neuropsychiatric Center, St. Petersburg, RussianFederation

Purpose: Studying of BEDC (benign epileptiform discharges of child-hood) in EEG of children with infantile cerebral paralysis (ICP).

Method: The study had 29 subjects aged between 3 months and 13 y.o.with brain organic lesions with and without motor impairment. Focal epi-lepsy was diagnosed in 9 on 15 of the I group subjects. ICP variations(Cerebral Palsy) distribution was as follows: tetraparesis in 10 children,hemiparesis in 2 children, and spastic diplegia in 2 children. During thestudy BEDC were diagnosed for the first time in subjects of both groups.A number of EEG assessments were carried out with once-a-month fre-quency. The exclusion criterion was diagnosed benign childhood epi-lepsy with central-temporal spikes.

Result: At the moment of the study launch EEG of all children showeddifferent alterations: delay in principal EEG rhythm generation; slow-wave focal activity; epileptiform complexes; sharp-slow wave; spike-slow wave. Dynamic EEG showed in all children participating in thestudy complexes of benign epileptiform discharges of childhood.

We noticed that appearance of these patterns in EEG coincided withclinical improvement of motor abilities in the I group subjects irrespectiveof brain lesions volume. In the I group subjects BEDC persisted through-out the entire study but showed certain mobility within brain cortex.

Conclusion: 1. BEDC in our study were transitory in children withoutmotor impairment.

2. Possibly BEDC might not impair motor abilities, but predict recov-ery from hereditary impairment of brain maturation

p558SEIZURE OCCURRENCE DURING PEDIATRIC EEGR. Gandelman-Marton, E. Heyman, and E. LahatAssaf Harofeh Medical Centre, Zerifin, Israel

Purpose: The ictal EEG can reveal previously unreported seizures andcorrect seizure classification and misdiagnosis of epileptic and nonepi-leptic seizures. Prolonged video- EEG recording can substantiallyincrease the diagnostic yield of seizures, but this test is less accessiblethan routine EEG.

The aim of our study was to identify the patients who are more likelyto experience a seizure during short-term EEG recording.

Method: We retrospectively reviewed the EEG recordings and medicalrecords of 294 patients, who were admitted to the Pediatric Departmentsin Assaf Harofeh Medical Center, and referred for a short-term EEG dur-ing a 5-year period following a seizure.

Result: Fifteen (5.1%) patients had seizures. The likelihood of seizureoccurrence was increased by history of seizures (OR 11.86, 95% CI 2.54 to55.37), abnormal neurological examination (OR 3.33, 95% CI 1.05 to10.55), and the presence of interictal epileptiform discharges (OR 10.07,95% CI 1.26 to 80.42). Treatment with antiepileptic drugs and mentalretardation were significantly more common among patients with seizures.

Conclusion: Children with a higher likelihood of a seizure during short-term EEG can be identified using data mainly obtained by history andneurological examination.

p559MISLEADING GENERALIZED REFRACTORY EPI-LEPSY IN YOUNG CHILDREN ‘‘EVOLVING’’ TO SYMP-TOMATIC OR PROBABLY-SYMPTOMATIC FOCALEPILEPSY; EPILEPSY SURGERY CANDIDATES LATEDETECTION POSSIBLE REASON TO BE CONSIDEREDA. Dalla-Porta, I. Maestro Saiz, J. M. Prats ViÇas,A. I. Fern�ndez-Bedoya, B. Mateos, L. Perez, and I. YurrebasoCruces University Hospital, Barakaldo, Spain

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Purpose: Refractory epilepsy in children should be treated precociouslyin order to avoid cognitive impairment among others. We present fourchildren with heterogeneous epileptic syndromes initially diagnosed ofmisleading generalized epilepsy.

Method: The four children aged from 18-months to 11 years, were stud-ied in our institution since neonatal age because of neonatal refractoryepilepsy. All of them underwent prolonged video-EEG recording andstructural neuroimaging and metabolic and genetic studies. Ictal semio-logic and electrographic changing patterns of recorded seizures were ana-lyzed along ‘‘epilepsy evolution’’.

Result: Metabolic and genetic studies were normal and structural neuri-maging revealed focal structural abnormalities in all cases, mostly notidentified until later stages. In early video-EEG recordings, symmetric orasymmetric epileptic spasms, generalized tonic or tonic-clonic seizuresor generalized myoclonic seizures with also generalized epileptiform ic-tal activity were recorded. In later stages, partial seizures such as, versive,dialeptic or automotor seizures with ictal focal epileptiforms patternswith or without secondary generalization were identified. At present, twoof the four patients are considered for epilepsy surgery and the other twowill undergo further functional and structural imaging studies just to beconsidered for surgery.

Conclusion: These epileptic children were initially diagnosed of gener-alized epilepsy as a result of initial clinical, video-EEG and structuralneuroimaging data. The epilepsy diagnostic in these patients, ‘‘evolved’’to symptomatic or probably-symptomatic focal epilepsy being then, con-sidered for epilepsy surgery. Children presenting signs suggesting gener-alized epilepsy in early stages should not be excluded for further studiesin order to determine if they are not real epilepsy surgery candidates.

p560THE RISK FACTORS OF RECURRENT FEBRILE CON-VULSIONB. H. ChaYonsei Unversity Wonju College of Medicine, Wonju, Korea

Purpose: Febrile convulsion is the most common type of seizure disor-der during childhood. We would like to evaluate the risk factors associ-ated with the recurrence of febrile convulsion.

Method: We retrospectively reviewed the medical records of 470 pedi-atric patients aged from 6 months to 5 years old, who admitted to theWonju Christian Hospital from January, 2008 to December, 2009 for feb-rile convulsion. We evaluated the recurrence rate of febrile convulsion byage of onset, duration of convulsion, seizure types, numbers of therecurred seizures during the initial 24 hours after the first convulsion, andfamily history of febrile convulsion or epilepsy.

Result: The ratio of male and female is 1.33: 1. The 69.8% of patientsexperience the first febrile convulsion between 12 and 23 months old.The cumulative rates of the recurred cases by the intervals between theinitial and recurred febrile convulsion are 51.9% at 6 month, 82.6% at 12month, and 89.8% at 24 month. The recurrence rate of febrile convulsionis 56.2% and when the first febrile convulsion occurs at the age less than12 months old, the recurrence rate (67.6%) is higher than the other age ofonset. There are no differences of recurrence rates by the duration of con-vulsion, seizure types, the numbers of recurred seizures during the initial24 hours, and the family history of febrile convulsion or epilepsy.

Conclusion: We should closely observe the patients the first febrile convul-sion occursat the age less than 12 months old and need toeducate the parents.

p561A GIRL WITH DRAVET SYNDROME AND IMMUNO-GLOBULIN G SUBCLASSES DEFICIENCYD. A. HasbiniRafic Hariri University Hospital, Beirut, Lebanon

Purpose: Dravet syndrome is characterized by recurrent prolonged con-vulsions usually associated with febrile illness. Many gene mutationshave been described behind the syndrome; however the mechanism ofwhy do seizures occur is not yet very clear. In addition, patients with Dra-vet seem to be predisposed to recurrent infections.

Method: In this article a girl who presented with prolonged convulsionsassociated with recurrent infections was diagnosed to have Dravet syn-drome in relation with a new mutation. In addition, she was found to haveimmunoglobulin g subclasses deficiency.

Result: The case illustrates that immunodeficiency may be behind thefrequent infections triggering the seizures in Dravet syndrome.

Conclusion: Treating the immunodeficiency might help patients withDravet syndrome in reducing the frequency of their illness and subse-quently their convulsions.

p562ATYPICAL FOR ROLANDIC EPILEPSYD. MusralinaAlmaty State Institute of Advanced Medical Education, Almaty,Kazakhstan

Purpose: To research the atypical for child benign partial epilepsy withcentro-temporal spikes (Rolandic epilepsy) and to define the treating tac-tics.

Method: A clinical case of child benign partial epilepsy with centro-temporal spikes at the girl.

Result: The child is from second pregnancy, which occurred with CMV,HSV in early period. The neonatal period - restless sleep and regurgita-tion. The first seizures occurred at 1 year and 10 months, the second epi-sode - was after the affective-respiratory paroxysm; the third - wastriggered by negative emotions. Seizures proceeded by an aura - anabdominal pain and depressed mood. Later they were joined by the par-tial attacks - ‘‘the numb’’ or the weakness in the left half of the face, lefthand, also the speech disorder during the attack, finished with the subse-quent generalization. Neuropsychological development was not affected.EEG (at the 2 years old) - benign epileptiform patterns of childhood inthe right temporal region. MRI of the brain - no significant changes. Shewas appointed to the drug valproic acid, which is replaced by topiromat,because of the lack of effect. In the dynamics the attacks were held,became more frequent. The EEG pattern was persisted, which was corre-sponded to rolandic epilepsy. After correction therapy (sul'tiam 5mg/kg)convulsions were managed. Catamnesis has demonstrated control of sei-zures and improvement of health during 4 years.

Conclusion: The presented clinical case shows an atypical variant ofRolandic epilepsy: early age of onset, debut with affective seizures, gen-eralized seizures, abdominal sensory aura, necessity to use the classic an-tiepileptic drugs.


p563RECOVERY IN CHILD WITH ACQUIRED APHASIAAND EPILEPSYS. M. Golubovic, and M. RisovicFaculty of Special Education and Rehabilitation, University ofBelgrade, Belgrade, Serbia

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Purpose: Boy was born such as first child from first pregnancy whichis ordinarily contorlled, maintained till 8. month with gynipral. Birthwas spontanious on the beggining of 9. month. WB (weight on birth)was 2150 gr. PD 45 cm, AS 8. Child is born with hearth defect(VSD).

Method: Psyhomotoric development was regular, begun to walk in 13.month, begun to speak in 11 month. He was operated and postoperatively,after waking up from anasthesia child had convulsional crisis (5–10 dur-ing day, lasting 10 days), hemyparesis lat. sin., lost of alredy developedabilities, divergent strabysmus, not controlled watering/miction and defe-cation. Since than, he gets antiepyleptics (targetol) because of EPY attacsin short sequences pariet-occipital right, and independent epyleptogenefocusis frontal-central-temporal

Result: Hemiparesis appeared as consequence of operation of hearth.Child was in coma for 7 days, lost eyesight, hearing and motorics. He hadEPY attacs.

Conclusion: Child had physical and logopedic tretament and he begunto contole defecation and miction. He wears plasters, alternatively on leftand right eye, because of strabismus. In neurological status is dominatingdamage of fine motorics. He is comunicative, cooperates, imitates actingof other people.

p564CORRELATIONS OF CLINICAL AND RADIOLOGICFEATURES IN PEDIATRIC PATIENTS WITH SCHIZEN-CEPHALYI. Kopyta, E. Jamroz, E. Kluczewska, and B. Sarecka-HujarMedical University Of Silesia, Sosnowiec, Poland

Purpose: Schizencephaly is a rare and severe congenital brain defect.Its’ etiology is not unequivocal. Aim of the study was to analyze correla-tions between clinical and radiologic features of schizencephaly in Polishpediatric patients.

Method: Study group consisted of 22 children (7 girls; 15 boys, aged: 3months-17 years). Patients were diagnosed at the Department of Neuro-pediatrics in Katowice.

Result: Epileptic seizures were observed in 64% of cases. In the fol-low-up the evolution of the seizures features was observed to the focalmotor seizures, primarily or secondarily generalized tonic-clonic sei-zures, tonic seizures, atypical absence. Eight of the patients were sei-zure-free. In 32% of patients the epilepsy was drug-resistant. Thegeneralized hypotonia was found in 14%, the spastic quadriparesis in55% and spastic hemiparesis in 32% of cases. We observed that seizureswere more frequent in the subgroup of children with bilateral schizen-cephaly than in unilateral schizencephaly (80% vs 29%, p=0.019). Thecorrelations between presence of the bilateral type II schizencephalyand occurrence of the seizures and atypical absence were found(p=0.004 and p=0.011, respectively).

Conclusion: There is a correlation between the type of schizencephalyand presence of the seizures in Polish pediatric patients. In most of thepatients schizencephaly leads to developmental retardation and epilepticseizures.

p565ANALYSIS OF THE EFFECTIVENESS POLYTHERAPYIN CHILDREN WITH PHARMACORESISTANT EPI-LEPSYN. Mendigaliyeva*, and D. Ayaganov�

*Almaty State Institute Of Advansed Medical Education, Almaty,Kazakhstan; and �Almaty, Kazakhstan

Purpose: Study of the effectiveness of polytherapy in children withpharmacoresistant epilepsy.

Method: We observed 25 children (11 girls, 14 boys) with pharmacore-sistant epilepsy, aged from 6 months to 14 years.

Result: The cases were symptomatic (16), idiopathic (6) forms of epi-lepsy and epileptic encephalopathies (3). Epilepsy in the background ofthe congenital malformation of the brain - 6, CP - 4, atrophic process - 3,after suffering a stroke - 2, after removal of the arachnoid cyst - 2, micro-cephaly - 1, CMV infection – 1, cause is not known - 6. Routine EEG:recorded epileptiform activity in 19 children, 6 children are not regis-tered. MRI: organic brain changes (16), with no apparent pathology (9).

Combinations of drugs: VPA + TPM (6); LEV + VPA (5); VPA +CBZ (3); VPA + LTG (2); VPA + LEV + TPM (2); VPA + OXC (1);VPA + TPM + CBZ (1); VPA + TETRACOSACTIDE (1); LTG + CBZ(1); LTG + LEV (1); LEV + TPM (1); TPM + CBZ (1). The effectivenessof therapy was observed in the form of complete control of seizures - 10,of 50% and above - 5, of 30–50% - 8, no effect - 2.

Conclusion: Pharmacoresistant Epilepsy occurs predominantly insymptomatic forms (64%). In 16 (64%) had organic brain changes. In40% (25 children) experienced complete control of seizures, improve-ment in 52% of children with no effect in 8% of children. It should benoted with sufficient effectiveness of polytherapy of pharmacoresistantepilepsy.

p566DOUBLE CORTEX SYNDROME AND EPILEPSYR. I. Teleanu*, M. Sandu�, D. Vasile�, D. Teleanu�, andD. Plesca�

*Carol Davila University of Medicine, Bucharest, Romania;�Dr V Gomoiu Children's Hospital, Bucharest, Romania; and�Emergency University Hospital, Bucharest, Romania

Purpose: Subcortical laminar heterotopia or ‘‘double cortex’’ is a cere-bral malformation with a defect in neuronal migration. Clinical manifes-tations are epilepsy and mental retardation. This disorder mainly affectsfemales. The XLIS gene is implicated and it is localized on the Xq22.3-23 chromosome.

Method: We present 3 rare cases diagnosed with subcortical laminarheterotopia.

Result: All patients had epileptic seizures, all patients had dysarthriaand one patient had mental retadation. MRI revealed in all patients a‘‘double cortex’’ aspect. Single Photon Emission Computed Tomography(SPECT) was performed in one patient.

Conclusion: In the past, such cases were categorized as cryptogenic epi-lepsy. Neuronal migration disorders associated with epilepsy can be rec-ognized by modern techniques, particularly MRI.

p567THE RESULTS OF NIGHT SLEEP ELECTROENCEPHA-LOGRAPHY AND MRI IN CHILDREN WITH EPILEPSYO. Klochkova, O. Kozhevnikova, L. Namazova-Baranova,A. Anikin, O. Logacheva, and V. AltuninScientific Centre of Children Health, Moscow, RussianFederation

Purpose: Assess the possibilities of long time electroencephalography(EEG) during the night sleep in diagnostics of epilepsy; to compare nightEEG results with magnetic-resonance imaging (MRI) findings in chil-dren with epilepsy.

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Method: 83 children (3 months–12 years old) with epilepsy underwentroutine EEG (REEG) on digital electroencephalography machines «Ni-cOne» (Nicolet, USA) during 20 minutes and then EEG during all night.Children under 3 years, some after 3 years underwent REEG during theday sleep. All patients had epilepsy, treated in out-patient department.All children had pathology according to perinatal anamnesis. Brain MRIwas done on Signa Twin speed Excite 1.5 T1 (GE, USA) in 54 patens.

Result: 37% of children had generalized or local epileptiform activityon REEG, and 69% - on night EEG. Only 23% patients had the general-ized epileptiform activity on routine EEG in comparison with 75% on thenight EEG, 11% patients had the focal epileptiform activity (REEG) incomparison with 22% during night EEG, and 9% had combined activityon REEG, and 43% - on night EEG. Only during night EEG we detected3 cases of seizures during investigations. 69% patients had alterations ofstructure of brain on MRI. Among structural disorders dominated localsubatrophy, arachnoid cysts and ventriculomegalia. We didn't see corre-lation between structural deviations on MRI and degree of night EEGchanges.

Conclusion: We recommend to carry out night EEG in children with sei-zures and pathological changes on REEG as more informative and usefulmethod, after first seizures or during epilepsy and without changes onREEG.

p568FEATURES OF THE PITUITARY HORMONAL REGU-LATION IN CHILDREN AND ADOLESCENTS WITHEPILEPSYZ. Viksna*, Z. Viksna�, J. Strautmanis�, A. Kovaldins�, andR. Ligere�

*Private, Jelgava, Latvia; �Children's University Hospital, Riga,Latvia; and �Paul Stradin's University Hospital, Riga, Latvia

Purpose: To evaluate changes in mean level of pituitary hormones- lu-teinising hormone (LH), follicle-stimulating hormone (FSH), and sex ste-roids- testosterone, oestradiole in blood serum in children andadolescents with epilepsy.

Method: The retrospective, case-control research envolved 53 patients(27 girls – 50.9% and 26 boys - 49.1%) aged 6 months until 18 years with"Idiopathic epilepsy’’ or "Symptomatic epilepsy’’. Age groups: 0–11years (17 girls and 20 boys), 12–18 years (10 girls and 6 boys). We deter-mined mean levels of LH, FSH, testosterone and oestradiole in bloodserum 30 minutes till 24 hours after the epileptic attack using the enzyme– linked immunosorbent assay.

Result: In 43 of the 53 observed patients (81.1%) we stated hormonalchanges. LH was reduced in 17 girls (62.9%) and 19 boys (73.1%) in theage group 0–11 years, increased in 2 boys (7.7%) in the age group but12–18 years. FSH was reduced in 6 boys (23.1%), but elevated in 2 girls(7.4%). Oestradiole was lower in 9 girls (33.3%) in the age group 0–11years. Testosterone was lower in 17 boys (65.4%) and 2 girls (7.4%).

Conclusion: Clinical observations reveal that children with epilepsyaged 0–11 years demonstrate pituitary and sex steroid hormonal altera-tions claiming for accurate, both clinical data, analysis.

p569EPILEPTOGENIC POTENTIAL OF SUPRATENTORIALBRAIN TUMORS IN CHILDRENA. A. Kholin, and V. S. KhalilovRussian State Medical University, Moscow, Russian Federation

Purpose: Symptomatic epilepsy is common in patients with supratento-rial brain tumors. Epileptogenesis depends on several factors including

tumor histology, location, changes in the peritumoral brain parenchymaand genetic predisposition. The aim of presented research was studyingepileptogenic potential of brain tumors of different histologic types inchildren.

Method: Among the pediatric patients investigated and treated in theNeurosurgical Department and Psycho-Neurological Department No2 ofRussian Children Clinical Hospital at the period 2006–2011 wererevealed 60 children with supratentorial brain tumors.

Result: The group of patient (n=60) consists of 28 girls and 23 boys(age range from 17 month till 17 years). 41 patients (68.3%) had symp-tomatic epilepsy. Among the patients were revealed: fibrillary astrocy-toma – 8 cases (all 8 patients had epilepsy), pilocystic astrocytoma 6(3), pleomorphic xanthoastrocytoma 5 (4), desmoplastic infantile astro-cytoma (DIA) 1 (0), protoplasmic astrocytoma 2 (1), ganglioastrocytom-a 5 (5), mixed glioma 3 (1), mixed ganglioglioma 2 (1), anaplasticganglioglioma 1 (0), desmoplastic ganglioglioma 1 (1), glioblastomamultiforme 2 (2), olygodendroglioma 1 (0), anaplastic ependymoma 6(3), choroid plexus papilloma 3 (0), atypical choroid plexus papilloma 1(1), choroid plexus carcinoma 1 (0), dysembryoplastic neuroepithelialtumor (DNET) 5 (5), primitive neuroepithelial tumor (PNET) 1 (1),atypical meningioma 1 (1), thalamic hamartoma 3 (3), meningioangi-omatosis – 2 (2).

Conclusion: Tumor types demonstrated obligate epileptogenesis were:fibrillary astrocytoma, ganglioastrocytoma, DNET, PNET, hamartoma,meningioangiomatosis, desmoplastic ganglioglioma, glioblastoma mul-tiforme and atypical meningioma. Pleomorphic xanthoastrocytoma wasepileptogenic in 80% of cases. Pilocystic and protoplasmic astrocy-toma, mixed ganglioglioma, anaplastic ependymoma had 50% risk ofepilepsy.

p570SEIZURE OUTCOME AFTER SERIAL AEDS HAVEFAILED FOR LACK OF EFFICACY IN FOCAL EPI-LEPSY IN CHILDREN WITHOUT AN ELECTROCLINI-CAL SYNDROMEE. Wirrell, K. Nickels, and L. Wong-KisielMayo Clinic, Rochester, MN, USA

Purpose: To determine outcome after serial AEDs fail for lack of effi-cacy in a population-based cohort of children with new-onset focal epi-lepsy without defined electroclinical syndrome (FE-ES).

Method: Children with new-onset FE-ES diagnosed from 1980–2009 inOlmsted County, MN were identified. Those followed >2 years followinginitial diagnosis were studied. We evaluated long-term outcome [strati-fied into favorable (seizure free >1 year at final follow-up and no prior re-sective epilepsy surgery), or poor (seizures in the final year of follow-upor prior epilepsy surgery)] in children where zero, one, two, or three ormore AEDs had been ineffective.

Result: 276/468 (59%) cases of newly-diagnosed pediatric epilepsy hadFE-ES, and 246 (89%) were followed for >2 years (median follow-up 10yrs). Of these, 160 (65%) achieved a favorable outcome. Favorable out-come was significantly less likely with increasing numbers of failedAEDs (p<0.001), being seen in 140/171 (82%) in whom none failed, 14/37 (38%) in whom 1 failed, 6/14 (42%) in whom 2 failed, and 0/24 (0%)in whom >3 AEDs failed. Although our numbers were small, childrenwith structural etiologies tended to have lower favorable outcome ratesthan those of unknown cause after one (25% vs 56%) or two AEDs (22%vs 80%) had failed (p=0.06).

Conclusion: FE-ES accounts for over half of pediatric epilepsy. Whiletwo-thirds have a favorable outcome after long-term follow-up, thechance of this outcome drops sharply after the first AED fails. Favorableoutcome was not seen in any child for whom >3 AEDs had failed for lackof efficacy.

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p571CYTOKINE LEVELS IN CHILDREN WITH IDIO-PATHIC PARTIAL AND GENERALIZED EPILEPSYTREATED WITH TOPIRAMATE AND VALPROIC ACIDF. M. Sonmez*, M. Serin�, A. Alver�, D. Zaman�,R. Aliyazicioglu�, A. Cansu�, and B. Anlar�

*Faculty of Medicine, Fatih University, ANKARA, Turkey;�Karadeniz Technical University, Trabzon, Turkey; and�Faculty of Medicine, Hacettepe University, Ankara, Turkey

Purpose: Antiepileptic drug (AED)s have been reported to affect theproduction and levels of certain cytokines. We investigated the effects ofvalproic acid (VPA) and topiramate (TPM) on the levels of interleukinIL1a, IL-1b, IL-1 receptor antagonist (IL-1RA), IL-2, 6 and 10, andTumor necrosis factor -a (TNF-a) in children with idiopathic epilepsy.

Method: Forty prepubertal children aged 6–12 (mean 8.3 € 1.7) yearswith idiopathic epilepsy were included. The patients were divided intotwo groups: 20 were treated with valproic acid (VPA) and 20 with topira-mate (TPA). The plasma levels of IL-1a, IL-1b, IL-1RA, IL-2, 6 and 10,TNF-a were measured before the initiation and at the 6th and 12thmonths of the treatment.

Result: In the VPA group, the levels of IL-1� significantly increased at12 months while the levels of IL-10 decreased at 6 months of treatmentcompared to values before treatment (p<0.05). There was no significantdifference in levels of IL-1, IL-6, TNF-a (p>0.05). In the TPM group,lower levels of IL-10 were observed at 6th and 12th months compared tothe onset of treatment (p<0.05).

Conclusion: VPA and TPM may affect cytokine levels. The next stepwould be to investigate the relation of these findings to the outcome ofepilepsy and response to treatment. In addition the clinical significanceof these effects on the immune system, autoimmunity, or inflammationneeds to be examined in a long-term, prospective manner.

p572COGNITIVE IMPAIRMENT AND CORTICAL REORGA-NISATION IN CHILDREN WITH BENIGN EPILEPSYWITH CENTRO-TEMPORAL SPIKES (BECTS)A. N. Datta*, N. Oser�, F. Bauder�, O. Maier§, F. Martin–,G. P. Ramelli**, M. Steinlin��, P. Weber*, and I. K. Penner�

*University Children's Hospital, Basel, Switzerland; �Universityof Basel, Basel, Switzerland; �Children's Hospital, Lucerne,Switzerland; §Children's Hospital, St. Gallen, Switzerland;–Children's Hospital, Aarau, Switzerland; **St. GiovanniHospital, Bellinzona, Switzerland; and ��University Children'sHospital, Berne, Switzerland

Purpose: Benign epilepsy with centro-temporal spikes (BECTS) isassociated with mild cognitive deficits, especially language impairment.Functional correlates of neuropsychological language deficits and theimpact of duration and antiepileptic treatment on language reorganisationwere investigated.

Method: 28 patients with BECTS and 19 healthy controls underwentneuropsychological testing and functional magnetic resonance imaging(fMRI).

Result: Although neuropsychological test results did only differ by trendbetween BECTS patients and controls, language laterality indices (LIs)in fMRI were significantly lower in patients than in controls. Particularlythe anterior language network with Broca's area and the supplementarymotor area (SMA) revealed the lowest LIs. Medication and duration ofepilepsy did not have any significant impact on language reorganisationand patients’ performances.

Conclusion: Language reorganization in BECTS patients obviouslyfocuses on the anterior language areas. These functional changes can beinterpreted as important compensatory strategies of the CNS to stabilizecognitive, especially language performances.


p573THE EFFECTIVNESS OF THE CARBAMAZEPINETREATMENT IN THE JUVENILE MYOCLONIC EPI-LEPSYB. Lorber, M. Vivoda, and D. B. VoduÐekUniversity Hospital Centre, Ljubljana, Slovenia

Purpose: To determine how often CBZ is used in the treatment of JME,despite it is considered inappropriate AED to use in this syndrome as itmay aggravate absence and myoclonic seizures characteristic of JME.Do patients that react favourably to CBS represent clinically differentsubtype of JME

Method: A retrospective study, using patient records from the specia-lised epilepsy clinic.

Result: From 96 patients with JME, 30 patients were treated with CBZat some stage in the course of therapy. Treatment was considered effec-tive and tolerable for 68% of the patients treated with CBZ and in 96% ofthe patients treated with other anti epileptic drugs (mostly VPA andLTG). Replacing CB with theoreticaly more appropriate therapy wasadvised for all the patients treated with CBZ. In 72% of these patients thenew treatment was considered effective and tolerable. Initial CBZ treat-ment of JME resulted in much less favourable prognosis than initial treat-ment with other AED.

Conclusion: Treatment of JME with CBZ is not uncommon and wasfound surprisingly effective in our group of patients. A part of it may beattributed to sub-optimal history taking regarding myoclonic seizureswhen JME was not properly diagnosed. But some of those patients mayalso represent a subgroup in the JME syndrome with major clinical fea-ture of JME but different response to AED and possibly different etio-pathological mechanisms.

p574AN EXPLORATION OF PRESCRIBING PRACTICE ANDPARENTAL USE OF EMERGENCY RESCUE MEDICA-TION TO PREVENT STATUS EPILEPTICUS IN CHIL-DRENC. M. Brand, and A. MclellanRoyal Hospital for Sick Children NHS Lothian, Edinburgh, UK

Purpose: To review current clinical practice around the prescribing ofemergency medications for prolonged seizures and whether parents whohave been trained can give and use it correctly.

Method: Data was collected prospectively for 6 months from a nurse ledclinic in a paediatric tertiary care centre in south east Scotland. Using anaudit questionnaire each patient attending the clinic had their emergencymedication prescription reviewed and assessed against the in-houseemergency medication prescribing pathway. Families were asked if theyhad used emergency medication and were assessed on whether they coulddemonstrate administration technique correctly.

Result: 49 patients were prescribed emergency medication forprolonged seizures. 47 (96%) patients had been admitted to hospital for

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prolonged seizures prior to prescription of emergency medication andonly 23 (47%) patients were admitted following prescription of emer-gency medication. 48 (98%) patients had been prescribed emergencymedication appropriately for prolonged seizures with 1 inappropriatelyprescribed for dose and only 34 (71%) had careplans completed. All par-ents had been taught administration technique, only 39 (79%) were ableto demonstrate the correct technique to deliver their child's prescribedemergency medication. 29 (59%) parents reported using it whenrequired, where they would have otherwise have called an ambulancewith 4 choosing not to use it and 16 unknown as it had not yet beenrequired.

Conclusion: Emergency medication for prolonged seizures is generallyprescribed appropriately, reduces the numbers of calls for an ambulancebut not all parents can correctly demonstrate the technique of administrat-ing emergency medication. Further work is required to ensure that carep-lans are always completed.

p575BLINK RELATED TEMPORAL SPIKES IN BENIGN RO-LANDIC EPILEPSYD. Allen, F. Cave, and F. KirkhamWessex Neurological Centre, Southampton General Hospital,Southampton, UK

Purpose: Age-related cortical hyper-excitability is considered to be anunderlying abnormality in the benign childhood focal epilepsy syn-dromes, resulting in functional spikes, benign seizure syndromes and insome cases ‘extreme SEPs’ – induced by finger tapping in some cases ofBRE. Only one previous case of blink related spikes in BRE has beenreported.

Method: We report the case of a girl who presented in status epilepticusaged seven. MR Imaging was normal. Subsequent infrequent seizureswere typical of BRE. EEG recordings revealed right mid-temporal spikesevoked only by spontaneous blinks. Left centro-temporal spikes occurredunrelated to blinking. All attempts to elicit right sided spikes by othermeans failed.

Result: A one hour video-EEG was recorded to characterise the spikes.998 left sided spikes were seen. 74 right sided spikes occurred at a meanpeak latency of 98ms (SD 9.3ms) after the onset of eye blinks, determinedwith EOG surface electrodes.

Conclusion: The findings suggest a different mechanism to the genera-tion of ‘extreme SEPs’. Strictly spontaneous blink related spikes weremost likely due excitation of the hyper-excitable right Rolandic cortex asa consequence of an excitatory interconnection from the pre-central cor-tex, supporting the theory of age-related cortical hyper-excitability inBRE. Yamagata T et al JNNP 1997; 63: 528–530 Nadkarni M et al Elec-troenc Clin Neurophysiol 1994; 90: 36–39 Manganotti P et al Brain1998; 121: 647–658.

p576SENSORY PROCESSING DISABILITIES IN CHILD-HOOD- ONSET GENERALIZED EPILEPSYE. Shahar*, S. Zlotnik2,3, S. Ravid*, and B. Engel-Yeger�

*Child Neurology Unit & Epilepsy Service, Meyer ChildrenHospital; �Department of Occupational Therapy, RambamMedical Center, Rappaport School of Medicine; and�Department of Occupational Therapy, Faculty of SocialWelfare and Health Studies, University of Haifa, Haifa, Israel

Background: Sensory processing disabilities (SPD's) are defined asinability to process sensory stimuli in a graded manner and to executebehaviors that are suitable to the degree, nature or intensity of the sensory

stimuli and may affect function, behavior and quality of life in a negativemanner. The sensory profile of children with generalized epilepsy has notbeen fully clarified.

Purpose: Assess possible sensory processing disabilities within all sen-sory modalities in children with generalized epilepsy.

Method: Patients: 52 children at the age of 6–10.9 years participatedincluding 22 patients with generalized epilepsy compared with 26 ageand gender matched controls. Methods:

A standardized Short Sensory Profile (SSP) questionnaire including38 items was given to caregivers to report, measured tactile and taste/smell sensitivities, movement sensitivity; underresponsive/seeks sensa-tion, auditory filtering, low energy/weak sensation and visual/auditorysensitivity.

Result: Children with generalized epilepsy had significantly higher sen-sory processing disabilities in all sensory modalities compared with con-trols and even showed extreme patters of underresponsive/sensationseeking.

Conclusion: The present study further delineates the growing bulk ofdata recognizing generalized epilepsy among children as a multi-facetedneurological disorder with diverse functional disabilities including sen-sory processing dysfunction, even showed extreme patters of underre-sponsive/sensation seeking.

p577SUDDEN UNEXPECTED DEATH IN CHILDREN ANDTEENAGERS WITH EPILEPSY: AN EPIDEMIOLOGI-CAL STUDYF. M. Besag*, R. Ackers�, E. Hughes�, L. Nashef§, W. Squier–,M. Murray�, and I. Wong***SEPT: South Essex Partnership University NHS FoundationTrust, Bedford, UK; �UCL, London, UK; �Guys and St Thomas’NHS Foundation Trust, London, UK; §Kings College Hospital,London, UK; –John Radcliffe Hospital, Oxford, UK; and **TheUniversity of Hong Kong, Hong Kong, Hong Kong

Purpose: To determine the rate of sudden unexpected death (SUDEP) ina population-based sample of children and teenagers aged 0–18 years.

Method: Data were extracted over the period 1.1.93 to 31.12.05 fromthe General Practice Research Database (GPRD), which includesapproximately 5% of the UK population and is representative of the gen-eral population. All subjects 0–18 years who had a diagnosis of epilepsyand were taking antiepileptic drugs were included. The cohort consistedof 6190 subjects representing 26,890 patient years. GP questionnaires,hospital letters and all other available data were examined in detail byan expert consensus panel. 151 deaths were identified. Cases were scru-tinised by a second panel including an epileptologist with a special inter-est in SUDEP to determine cases of definite, probable and possibleSUDEP.

Result: Eleven subjects, 2- 17 years of age (8M, 3F) died from definite(2), probable (3) or possible (6) SUDEP. Seven had significant underly-ing neurological/neurodevelopmental problems: Ohtahara syndrome (1),cerebral palsy (3) and other underlying neurological abnormalities (3).However, the remaining four had no evident underlying disorder apartfrom the epilepsy. The SUDEP incidence rates were: definite and proba-ble 1.9 per 10,000 person-years (95% CI 0.6, 4.3), possible 2.2 per10,000 person-years (95% CI 0.8, 4.9), combined definite, probable andpossible 4.1 per 10,000 person-years (95% CI 2.0, 7.3).

Conclusion: SUDEP can occur in both children with pre-existing neuro-logical abnormalities and those who appear to be neurologically normalapart from the epilepsy. However, the SUDEP rate was low in this popu-lation-based study.

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p578EVALUATION OF EFFICACY OF VAGUS NERVE STIM-ULATION IN CHILDREN. PROSPECTIVE RESULTSFROM A SINGLE CENTER IN LEBANONG. A. Hmaimess*, A. Baydoun�, I. Dabaj�, and H. Mansour�

*Saint George University Hospital Medical Center, Beirut,Lebanon; �Beirut, Lebanon; and �Brussels, Belgium

Purpose: Vagus nerve stimulation (VNS) is an established treatmentmodality for patients with medically refractory epilepsy. The purpose ofthis study was to prospectively evaluate the efficacy of VNS in a consecu-tive cohort of children implanted over a two years period at a single Med-ical Center in Lebanon.

Method: Children with refractory epilepsy not candidates for epilepsysurgery and implanted with a VNS were prospectively evaluated. Allchildren had a full evaluation, including CCTV/EEG monitoring, epi-lepsy protocol MRI, and metabolic and genetic testing when indicated.The responder rate (>50% reduction in seizure frequency) was assessedat 6, 12 and 18 months following implantation. In addition, the quality oflife and usefulness of the magnet was assessed.

Result: 40 children (range; 6 months–18 years) were implanted. Theresponder rates were 50%, 63% and 67$ at 6, 12 and 18 months followingimplantation, respectively. In addition, 49% of children had ameliorationin seizure severity, including shorter seizure duration in 30% and shorterpost-ictal state in 26%. 56% of children had an improvement in the qual-ity of life with an improvement in alertness and in the level of social inter-actions. The magnet was reported to be useful by 47% and the number ofAEDs was reduced in 13% of those children.

Conclusion: VNS is a good treatment option for children with refractoryepilepsy when conventional therapy fails. Prospective studies are neededto better delineate the characteristics of children most likely to benefitfrom VNS implantation.

p579A SHORT COURSE OF ACTH REGIMEN FOR TREAT-ING REFRACTORY CHILDHOOD SEIZURESH. H. AbdeldayemFaculty of Medicine, Alexandria University, Egypt

Purpose: Childhood seizures that are refractory to conventional antiepi-leptic drugs (polytherapy) are distressing to physicians and parents. Adre-nocorticotropic hormone (ACTH) injection (IM) has been suggested to beused for treating of theses refractory epilepsy in young children in a shortcourse regimen (6 weeks). Subjects: Young infants and children: from 6months age up to 4 years age. Inclusion criteria: 1- Refractory epilepsy withthe use of at least 2 anti-epileptic drugs, 2- Cases with generalized tonic-clonic epilepsy, myoclonic epilepsy, tonic, atonic or mixed epilepsy.

Method: 6-weeks of ACTH treatment is followed by 6 months followup thereafter. The study will enroll male and female children up to age of4 years old with refractory epilepsy. Patients will receive ACTH (Synac-tan IM* Novartis) in dosage of 1 mg every alternate daily for 4 doses then0.5 mg every alternate daily dosage for 4 doses then gradual decrease by0.1 mg on alternate daily dosage for 4 doses per each dose (0.4mg, 0.3mg, 0.2 mg, 0.1mg respectively). after 2 weeks, ACTH should be toppeddue to non tolerable side effects or failure of good response as regard fitscontrol NB., EEG recording are performed before and after full ACTHregimen treatment.

Result: ACTH was used by IM injection in 60 epileptic children usingunsuccessfully 2 or more antiepileptic drugs. After 2 weeks of treatment92% of cases showed improvement (less number of fits). After 6 weeksof treatment 89% of cases showed full remission. Minor Side effects (tol-erable) as cushinoid faces (81%), irritability (12%) and gum blue pig-mentation (14%). However, only 2 cases showed marked hypertensionup to hospital admission. After 6 months, recurrence of fits occurred in

18% of studied cases. These cases responded to the second regimencourse of ACTH injections.

Conclusion: The use of ACTH in our new regimen for refractory sei-zures - other than infantile spasms- over 6 weeks will give the followingadvantages over the other anti-epileptic drugs: 1- rapid response - within2 weeks - 2- short duration of management - within 6 weeks- 3- less Side-Effects- almost tolerable 4- after 6 months, few cases showed recurrencewith the need of new 6 weeks course 5- parents are more satisfied withthe short course treatment and the rapid response 5.

p580CONTINUOUS INTERICTAL EPILEPTIFORM ACTIV-ITY AND ITS EFFECT ON COGNITION AND BEHAV-IOR OF CHILDRENI. S. Ivanov, I. Pacheva, I. Sotkova, A. Petkova, P. Dimova,T. Markova, I. Ivanova, and E. TimovaPlovdiv Medical University Hospital ‘‘Sv. Georgi’’, Plovdiv,Bulgaria

Purpose: To investigate epilepsy, cognition and behavior in pediatricpatients with continuous interictal epileptiform activity (CIEA) and findprognostic factors.

Method: Among 577 pediatric patients with epilepsy 29 (5.03%) withCIEA were found. Six of them were excluded because of IQ/DQ <50%.The remaining 23 children (13 male) were thoroughly investigated.

Result: Epilepsy was partial in 22 of the 23 patients (symptomatic in 12,cryptogenic- 5, idiopathic- 5). CIEA was diagnosed at mean age 6y11mo. CIEA was focal in all infants, mostly temporal, unilateral or bilat-eral, awake and/or in sleep. Diagnosis of CIEA was associated with clini-cal findings in 21 patients: worsening of seizures (10 patients),worsening of language (14 patients), visual-spatial perception (11), finemotor tasks (12), vigilance (10), attention (13), hyperactivity (5), aggres-sion (2), and other behavioral changes (5). AED, mostly VPA, BDZ andLEV, mainly in combinations of 2 (8 patients) or 3 (10), and CS in 2patients, abolished CIEA in 14 cases. Improvement of cognition andbehavior after adequate treatment was observed in 9 patients, 8 of themwith improved seizures and 6 - with abolished CIEA. Unfavorable cogni-tive/behavioral prognosis in patients with CIEA was associated with peri-natal and early infantile etiology, early onset of epilepsy (mean 3y 4mo,range 6mo–7y 9mo), early diagnosis of CIEA (mean 2y 5mo, range 2y5mo–8y 7mo), secondary generalized seizures and epileptic status.

Conclusion: CIEA is an alarming symptom in partial epilepsies withunfavorable effect on cognition and behavior, especially in early onsetsymptomatic epilepsies.

p581PHOTOSENSITIVITY AT DIFFERENT FORMS OF EPI-LEPSY AND THERAPY FEATURESI. Schederkina*, and V. Karlov�

*Morozovskay Children Hospital, Moscow, Russian Federation;and �Moscow State of Medicine and Dentistry University,Moscow, Russian Federation

Purpose: Photoparoxysmal reaction (PPR) is evaluated as generalizedepileptiform activity spike- and polyspike-slow wave, occurring underrhythmic photostimulation and may be registered in different forms ofepilepsy. Aim: to evaluate frequency of PPR among children with epi-lepsy, effect of different anticonvulsants on PPR.

Methods: Clinical, electroencephalography, video-EEG sleep monitor-ing.

Results: 116 children with different forms of epilepsy and PPR in EEG(68 boys and 48 girls) were observed. Forms of epilepsy were registered:

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idiopathic generalized -24%, juvenile myoclonic and cryptogenic focal -20.6% each, childhood and juvenile absence -8.6% each, Jeavans syn-drome and symptomatic focal -5.1% each, occipital -3.4%, atypical ro-landic and complex febrile seizures - 1.7% each. In 22.4% of cases PPRwas registered at onset of epileptic seizures, 60% - during observetion,3.5% - during anticonvulsant dose decrease, 13.7% - after cessation ofanticonvulsant therapy. PPR was registered isolated in 22% of cases, wascombined with generalized epileptiform activity -74%, frontal and tem-poroparietal -28% each, occipital -18%. Seizure types were: tonic-clonic-38%, myoclonic -29.3%, absence -22.4%, secondary generalized andcomplex focal -20.6% each. One third of children had a combination oftypes of seizure. In 75.8% clinic-encephalographic remission with mono-therapy: valproates -52.2%, topiramate -18%, keppra -12.5%, ethosuxi-mid - 5.6%, carbamazepin, trileptal -4.5%. In 24.1% was duotherapy:valproate+keppra -37.9%, valproate+topiramate -24%, valproate+eth-osuximid -21%.

Conclusion: Idiopathic generalized forms of epilepsy prevailed amongchildren with PPR, one third of cases showed combination of seizuretypes. The most effective in monotherapy: valproates, topiramate, kep-pra. 100% efficiency for duotherapy: valproates with keppra, ethosuxi-mid and topiramate.

p582COGNITIVE FUNCTION IN CHILDHOOD EPILEPSY-ASINGLE CENTER STUDYJ. Park*, M. Yum*, H. Choi*, T. Ko*, and H. W. Kim�

*Asan Medical Center, Seoul, Korea; and �Asan MedicalCenter, Seoul,

Purpose: Epilepsy is significantly associated with cognitive function.Many factors such as the etiology of epilepsy, onset age, antiepilepticdrugs, can affect the cognition of the children with epilepsy. The aims ofthis study were to describe the cognitive performance in children withepilepsy and to determine frequency of cognitive impairment, and epi-lepsy-related factors correlating with cognitive impairment in a singletertiary center in Korea.

Method: From January 2006 to March 2011, 322 children who werediagnosed with epilepsy were retrospectively enrolled. Korean EducationDevelopment Institute-Wechsler Intelligence scale for Children (KEDI-WISC) was used to measure the cognitive function. Epilepsy-related fac-tors (onset age, etiology, seizure type, frequency of seizure, antiepilepticdrug medication) were analyzed to test the association with the level ofcognition. v2 test or Fisher's exact T-test, logistic regression were usedfor statistical analysis.

Result: Cognitive function was considered within normal in 146(45.3%), borderline, in 18 (5.6%), mild mental retardation (MR) in 47(14.6%), more severe MR in 111 (34.5%). 176 of 322 (54.7%) had sub-normal intelligence. Early onset (<5 yr), symptomatic etiology, frequentseizure at the time of test, the number of antiepileptic drugs, the historyof epileptic encephalopathy were each strongly associated with low levelof cognitive function (p<0.05). The abnormal EEG finding has no associ-ation with the subnormal IQ (p>0.05) in this study.

Conclusion: Epilepsy is inseparably linked to cognitive function. Expla-nations for these associations include the impact of the underlying struc-tural/metabolic lesions, the effects of seizures and antiepileptic drugs, aspotential mechanisms.


p583WHAT IS AN ATTACK (SEIZURE)?V. Karlov*, V. Gnezdizky*, and A. Pevzner�

*Moscow State of Medicine and Dentistry University, Moscow,Russian Federation; and �Russian Cardiology Research andProduction Complex, Moscow, Russian Federation

Purpose: To define the biological meaning of cerebral attacks.

Method: First block. We investigated 52 patients with attacks, whosediagnoses have not been determined after the patients were examined bya cardiologist and neurologist. EEG sleep monitoring, EEG after sleepdeprivation and the long passive orthostatic probe were used.

Second block. We studied mechanisms of paroxysmality in patients ofwith epilepsy (E), panic attacks (PA) and a combination of epilepsy andpanic attacks (E+), 30 patients in each group. The quality of autonomicregulation was studied via the registration of skin sympathetic response(SSR) and comparing this data with the EEG.

Third study block. We studied 10 epileptic men with recurrent GTCseizures and alternative dysphoria.

Result: First Block. As a result, 47 out of 52 patients (90.3%) werereported to have definite type of attacks. An interictal EEG pattern thatreflects cerebral mechanisms common to different seizures was estab-lished.

Second block. One of the main results is compensatory strain of thehomeostatic stabilizing mechanism under a loading trial.

MMPI showed full accordance with clinical data: the seizure serves asa factor eliminating of dysphoria.

Conclusion: An initial defect on any systemic level stimulates homeo-static compensatory mechanisms. Under the influence of certain endoge-nous or exogenous factors, the homeostatic status can reach the criticallevel (extreme strain, overstrain). The biological essence of attack (sei-zure) is an acute breakdown of the overstrained homeostatic mechanismthat mobilizes vital resources and leads to the re-compensation of homeo-stasis.

p584GRANULE CELL DISPERSION IS ASSOCIATED WITHMORE SEVERE NEURONAL LOSS IN MESIAL TEMPO-RAL LOBE EPILEPSY WITH MESIAL TEMPORALSCLEROSISL. O. S. F. Caboclo*, R. S. D. C. Neves*, A. P. Jardim*,R. S. Centeno*, C. L. P. Lancellotti�, C. A. Scorza*,E. Cavalheiro�, and E. M. T. Yacubian**Universidade Federal de Sao Paulo, Sao Paulo, Brazil; �SantaCasa de Sao Paulo, Sao Paulo, Brazil; and �UNIFESP, SaoPaulo, Brazil

Purpose: To analyze retrospectively a series of patients with mesialtemporal lobe epilepsy (MTLE) and mesial temporal sclerosis (MTS)and to investigate the possible association of granule cell dispersion(GCD) with clinical data, patterns of MTS and surgical prognosis.

Method: Sixty-six patients with medically refractory MTLE and unilat-eral MTS were included in the study. All patients were submitted to ante-rior temporal lobectomy. Tissue obtained in surgery, as well as thirteencontrol specimens, was studied. Quantitative neuropathological evalua-tion was performed on NeuN-stained hippocampal sections. MTS typeswere defined according to criteria established by Blumcke et al. (ActaNeuropathol 2007; 113: 235–244). GCD was considered present when:(a) the width of the granule cell layer (GCL), assessed in the straight partsof the layer, was wider than 120 lm; (b) granule cells did not remain inclose opposition to one another; and (c) the normal clear boundarybetween the molecular layer and the GCL was not maintained (El Bahh Bet al. Epilepsia 1999; 40: 1393–1401).

Result: GCD was present in 45.5% of cases. We found no correlationbetween clinical variables and GCD. Except for MTS type 2 (‘‘CA1 scle-rosis’’, found in four patients without GCD and no patients with GCD),

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no-GCD and GCD groups did not differ with respect to the types of MTS.More severe neuronal loss was found in patients with GCD. Surgical out-come was similar in both groups.

Conclusion: GCD was associated with more severe hippocampal neuro-nal loss, but was not a predictor of surgical outcome.

p585WHAT IS THE ROLE OF NEUROMEDIN N DURING SEI-ZURES?K. Maes, A. Van Eeckhaut, Y. Michotte, and I. SmoldersVrije Universiteit Brussel, Brussels, Belgium

Purpose: Neuropeptides play an important role when the central ner-vous system is challenged, such as during epileptic seizures. In order toobtain better insights in the peptidergic effects involved in limbic epi-lepsy, we monitor the concentration dynamics of some neuropeptides inthe rat hippocampus during seizures. Furthermore, we aim to unravel themodulatory effects of the peptides on the excitability of the brain. Thiscan lead to the identification of innovative peptidergic targets for newanti-epileptic drugs. In this study we focus on neuromedin N, because itsrole in epilepsy is elusive.

Method: During a microdialysis experiment, neuromedin N content ismeasured in the rat hippocampus before, during and after pilocarpine-induced limbic seizures using nano liquid chromatography-electrosprayionisation-tandem mass spectrometry (nano LC-ESI-MS/MS). In ongo-ing experiments, the possible anticonvulsive effects of neuromedin N areinvestigated in rat and mouse models for partial seizures with secondarygeneralization.

Result: The concentration of neuromedin N in rat basal hippocampal di-alysates is found to be near the limit of detection of the method (1 pM).Therefore, further optimisation of the microdialysis, LC and MS/MSparameters is necessary to allow more sensitive and accurate measure-ments. During seizures we observe a 40-fold increase in the concentrationof neuromedin N, which returns to baseline at the end of the experiment.

Conclusion: These preliminary results show that the release of neurom-edin N is increased in the rat hippocampus during seizures. Study of thepossible anticonvulsive effects of neuromedin N is part of ongoingresearch.

p586INDIAN HERBAL DRUGS IN EXPERIMENTAL MOD-ELS OF EPILEPSYY. K. Gupta, K. H. Reeta, M. Pahuja, and J. MehlaAll India Institute of Medical Sciences, New Delhi, India

Purpose: Indian medicinal plants used in CNS disorders, as nervinetonic in traditional system of medicine and also have significant antioxi-dant activity was evaluated against experimental models of seizures andseizure induced cognitive impairment.

Method: Seizures were produced by acute pentylentetrazole (PTZ),maximal electroshock (MES), kainic acid induced seizures and PTZ-induced kindling in rats. Cognitive function was assessed by elevatedplus maze and passive avoidance tests. Oxidative stress markers (MDAand GSH) and cholinesterase (AChE and BChE) activity were also evalu-ated. Interaction profile of the plant extracts with standard antiepilepticdrugs (AEDs) were also studied.

Result: Hydroalcoholic extracts of Acorus calamus (200 mg/kg, p.o),Anacyclus pyrethrum (500 mg/kg, p.o), Benincasa hispida (1000 mg/kg,p.o), Orchis mascula (1000 mg/kg, p.o) and Zizyphus jujuba (1000 mg/kg, p.o) showed protection against generalized tonic-clonic seizures(GTCS) and hind-limb extension (HLE) in PTZ and MES models,

respectively. The plant extracts also showed protection against seizuresinduced cognitive impairment, oxidative stress and normalized the cho-linesterase activity. Curcumin (300 mg/kg, p.o.) protected against kainicacid induced seizures and oxidative stress. Pre-treatment with curcuminfor 21 days prevented the cognitive impairment induced by AEDs (phe-nytoin, phenobarbitone and carbamezepine). Single dose administrationof curcumin potentiated the anti-epileptic effect of valproate, phenytoin,phenobarbitone and carbamazepine in experimental models of seizures,without altering serum levels of these AEDs.

Conclusion: The protective effect of the plant extracts against seizuresand seizure-induced cognitive impairment may be due to their anti-oxi-dant potential. The findings suggest their potential as an adjuvant to an-tiepileptic drugs.

p587ELECTROPHYSIOLOGICAL RESPONSES TO VAGUSNERVE STIMULATION IN RATSL. Mollet, R. Raedt, J. Delbeke, R. El Tahry, V. De Herdt,A. Meurs, W. Wadman, K. Vonck, and P. A. J. M. BoonNeurology, Neuroscience, Ghent, Belgium

Purpose: Vagus nerve stimulation (VNS) for refractory epilepsyrequires optimization of stimulation parameters to improve outcome.VNS exerts its effect by activating afferent, fast-conducting fibers. Thereis however a clear need for an objective parameter reflecting effectivestimulation. We recorded electrophysiological responses to stimulationof the vagus nerve.

Method: Rats were implanted with a stimulation electrode around theleft cervical vagus nerve. Recordings were made using point electrodesplaced on the vagus nerve rostral to the stimulating cathode. The vagusnerve was stimulated under anesthesia with a biphasic pulse (5ls/phase).

Result: The electrophysiological response consisted of an early and alate component, identified as respectively an afferent compound actionpotential (CAP) and a far field potential of the larynx motor evokedpotential (LMEP), with a conduction velocity of respectively 32.5€2.5m/s and 33.3€1.3m/s. The I50% for the CAP and LMEP (respectively1.9€0.3mA and 1.6€0.1mA) were not significantly different. Meanlatency for the CAP and LMEP at 1.3€0.3mm rostral to the stimulatingcathode, were 0.4€0.1ms and 2.0€0.2ms respectively. At 3.1€0.6mm ros-tral to the stimulating cathode, a difference in response latency was mea-sured for the CAP, but not for the LMEP.

Conclusion: Short biphasic pulses with an intensity of 1.5–2.5mA acti-vate fast-conducting vagal fibers. Our set-up can be used to evaluate theeffects of different stimulation parameters at the level of the cervicalvagus nerve in epilepsy models.

p588CONVULSANT ACTIVITY OF PILOCARPINE IN MICEIS LIMITED BY MULTIDRUG-TRANSPORTERS ATTHE BLOOD-BRAIN BARRIERM. Bankstahl, K. Rçmermann, J. P. Bankstahl, and W. LçscherUniversity of Veterinary Medicine Hannover, Hannover,Germany

Purpose: Pilocarpine is widely used to induce status epilepticus inrodents resulting in development of chronic epilepsy. Aim of this studywas to evaluate the influence of the multidrug-transporters P-glycopro-tein (Pgp, Mdr1) and breast cancer resistance protein (Bcrp) on brainuptake and convulsant activity of pilocarpine.

Method: Cumulative dose of pilocarpine needed to induce status epilep-ticus in wild type (WT, FVB/N) and Mdr1a/b(-/-) mice of either genderwas determined. The pharmacokinetic profile following a single

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pilocarpine injection in WT mice was recorded over 120 minutes.Finally, brain uptake of pilocarpine was compared in Mdr1a/b(-/-),untreated WT mice and WT mice pretreated with the dual Pgp/Bcrp-inhibitor tariquidar (15 mg/kg). Transport of pilocarpine by Pgp and/orBcrp1 was further investigated in in-vitro concentration equilibriumtransport assays using Mdr1a- and Bcrp1-overexpressing cells.

Result: In Mdr1a/b(-/-) mice, a significantly lower dose of pilocarpine(297 € 68 mg/kg) was sufficient to induce status epilepticus compared to453 € 154 mg/kg in WT mice. This difference was gender-independent.Maximal pilocarpine levels in brain tissue were reached after about 20minutes. Plasma elimination half-life was 35 minutes. Pilocarpine brainuptake was only slightly increased in Mdr1a/b(-/-) mice compared to WTmice, whereas tariquidar-treated animals displayed a marked increase(~80%) in pilocarpine brain uptake. Our in-vitro studies showed effectivetransport of pilocarpine by Bcrp and, less pronounced, by Pgp.

Conclusion: Our data reveal that Bcrp and, to a lesser extent, Pgp play arole in limiting the brain entry of pilocarpine and hereby influence itsconvulsant properties.

p589RUTIN REDUCES NEUROINFLAMMATION AND NEU-RONAL DEGENERATION IN THE RAT BRAIN AFTERKAINIC ACID-INDUCED STATUS EPILEPTICUSM. Golechha*, U. Chaudhry*, D. Saluja*, and D. Arya�

*Dr. B R Ambedkar Center for Biomedical Research, New Delhi,India; and �All India Institute of Medical Sciences, New Delhi,India

Purpose: This study was undertaken to investigate the neuroprotectiveeffects of rutin (vitamin P) on kainic acid (KA)-induced status epipeticusin rats. Oxidative stress and inflammation is an important event, play acrucial role in neurodegenerative diseases. Rutin has been shown to haveantioxidant and anti-inflammatory actions, and thus was tested for itsbeneficial effects using KA-induced status epipeticus in rats.

Method: Male wistar rats were treated with rutin at doses of 25, 50 and100 mg/kg, i.p. for 7 successive days before KA administration. Ratswere observed for behavioral changes and incidence and latency of con-vulsions. The effect of rutin on KA-induced cell injury was also investi-gated on several cellular pathways including neuronal plasticity (RhoA),neurodegeneration (Caspase-3), and inflammation (COX-2) in PC12cells and microglial BV-2 cells.

Result: Pretreatment with rutin (50 and 100 mg/kg, i.p.) significantlyincreased the latency of seizures as compared to the vehicle-treated KAgroup. Rutin was effective to protect PC12 cells and BV-2 cells fromKA-injury in a dose-dependent manner. It decreased the release of Ca2+,reactive oxygen species, and MDA from PC12 cells. Western blot analy-sis revealed that rutin significantly reduced ERK1/2, p38 mitogen-acti-vated protein kinases, Caspase-3, and COX-2 expression in both cellsand RhoA expression in BV-2 cells. Furthermore, rutin was able toreduce PGE2 production from both cells under KA-stimulation.

Conclusion: Taken together, it suggests that rutin could protect KA-induced brain injury through anti-inflammatory and partially anti-oxida-tive mechanisms.

p590DOES FEEDING BEHAVIOUR OF GENETIC ABSENCEEPILEPSY RATS DIFFER FROM CONTROL WISTARRATS?M. Gulcebi Idriz Oglu*, S. Ketenci*, T. Karamahmutoglu*,D. Akin�, and F. Onat**Marmara University School of Medicine, Istanbul, Turkey; and�Istanbul Bilim University School of Medicine, Istanbul, Turkey

Purpose: Neuropeptide Y (NPY) and leptin are the two peptidesinvolved in feeding behaviour, seizure, cardiovascular regulation andstress. NPY expression has been shown to enhance in low diet ratswhereas plasma leptin concentration decreased. Overexpression of NPYby recurrent epileptic seizures particularly in hippocampus could beconsidered as a protective mechanism against to epileptic activity (Vez-zani A and Gnther S. Neuropeptides 2004; 38:245–252). AlthoughNPY has been shown to suppress absence seizures in genetic absenceepilepsy rats from Strasbourg (GAERS), GAERS show resistance toelectrical kindling. This study aimed to compare the main metabolicparameters of GAERS and Wistar animals as well as plasma leptin andNPY levels related to involvement in the resistance mechanism of GA-ERS to kindling.

Method: Adult male GAERS (n=6) and control Wistar rats (n=5) wereused. Following one week acclimation in the metabolic cages, daily bodyweight, food and water intake, urea and feces amounts of the animalswere recorded for one week and blood samples were stored until the mea-surement of leptin and NPY levels.

Result: Mean body weight, food intake and feces amount of the GAERSwere lower than Wistar rats (22%, 26.3%, and 13.3% respectively)whereas water intake and urea measurement results not. The NPY andleptin levels have not been measured yet.

Conclusion: These results can be indicative for different leptin andNPY levels. We also plan to analyze protein expression of NPY in thehippocampus of the GAERS and Wistar rats in the future.

p591EFFECT OF ANACYCLUS PYRETHRUM ON PENTY-LENETETRAZOLE-INDUCED KINDLING, COGNI-TION, OXIDATIVE STRESS AND RHO-KINASE IIEXPRESSION IN MICEM. Pahuja, K. H. Reeta, M. Tripathi, and Y. K. GuptaAll India Institute of Medical Sciences, New Delhi, India

Purpose: Anacyclus pyrethrum a perennial, procumbent plant has beenreported to exhibit anticonvulsant activity. In the present study, the effectof hydroalcoholic extract of A. Pyrethrum root (HEAP) on pentylenetet-razole (PTZ) induced kindling, spatial memory, oxidative stress and rhokinase II was assessed.

Method: Male albino mice (25–30 g) were used in the study. PTZ-35mg/kg, i.p was administered to induce kindling and PTZ-70 mg/kg, i.pchallenge was given, 7 days post kindling. HEAP (100, 250 and 500mg/kg, orally) were administered for 35 days. Spatial memory wasassessed using Morris water maze. The oxidative stress parameters werealso assessed by estimation of malondialdehyde (MDA) and reducedglutathione (GSH). Rho kinase II expression was studied by westernblotting.

Result: HEAP pre treatment showed a significant dose-dependentincrease in the myoclonic jerk latency and delay in development of kind-ling, which is comparable to that of valproate treated group. 30% and20% mortality was observed in PTZ group and HEAP 100 mg/kg group,respectively. Whereas, no mortality was observed at higher doses (250and 500 mg/kg). Pre-treatment with HEAP increased the number of plat-form crossings on water maze test, as opposed to the PTZ group, thusshowing protection against memory deficit. HEAP pre treatment alsoattenuated the oxidative stress induced by kindling. PTZ increasedROCK II expression whereas, HEAP pre treatment attenuated theincrease in ROCK II expression.

Conclusion: HEAP pre treatment showed antiepileptic effect in PTZinduced kindling in mice and also protected cognitive impairment, oxida-tive stress and showed rho kinase II inhibitory activity in PTZ kindledmice.

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p592THE PRESENCE OF THE CAV3.2 R1584P MUTATION ISASSOCIATED WITH RESISTANCE TO KINDLINGINDUCED CHANGE IN THE TRN NEURON FIRINGPATTERNN. Carcak*, T. Zheng�, N. C. Jones�, L. Van Raay�, K. Powell�,F. Onat�, and T. J. O’Brien�

*Istanbul University Faculty of Pharmacy, Istanbul, Turkey;�University of Melbourne, Melbourne, Australia; and �MarmaraUniveristy School of Medicine, Istanbul, Turkey

Purpose: Genetic Absence Epilepsy Rats from Strasbourg (GAERS, awell validated model of idiopathic generalized epilepsy, carry a gain-of-function mutation (R1584P) in the T-type calcium channel, Cav3.2,which contributes the epileptic phenotype in F2 progenies derived fromGAERS and non-epileptic control (NEC) rats. GAERS are resistant tothe development of secondarily generalized seizures with amygdala kind-ling. We investigated whether the Cav3.2 (R1584P) mutation influenceskindling resistance and the effect of kindling on neuronal firing in thereticular nucleus of the thalamus (TRN).

Method: Double crossed (GAERS · NEC) F2 generation rats homozy-gous (m/m) or null (+/+) for the Cav3.2 (R1584P) mutation were kindledtwice daily to a maximum of 30 stimulations. Thereafter extracellularsingle neuronal recordings from TRN were performed in vivo under neu-ralept anaesthesia.

Result: The rate of behavioural seizure progression was not differentbetween the genotypes (p>0.05). However, the rats null for the mutation(+/+) appear to have longer and faster progression of the electrographicseizure durations during kindling compared to those homozygous for themutation (m/m) (p= 0.039). The TRN firing frequency in rats null for theCav3.2 (R1584P) mutation was significantly lower (+/+: 5.1€1) than ratshomozygous for the Cav3.2 (R1584P) mutation (m/m: 11.7€5)(p=0.03).A decrease in firing frequency is correlated with an increase in theamount of burst firing (R2=0.52).

Conclusion: These results indicate changes in neuronal firing patterns inthe thalamus in the progression of amygdala kindling, and support a rolefor the Cav3.2 R1584P mutation in the kindling resistance of GAERS.

p593AN ANTAGONIST OF GABAB RECEPTORS EXHIBITSPROCONVULSANT ACTION IN BOTH AGE- ANDMODEL-DEPENDENT MANNERP. MareÐInstitute of Physiology, Academy of Science, Prague 4, CzechRepublic

Purpose: Agonists of GABAB receptors exhibit mixed anti- and procon-vulsant action. Anticonvulsant action is more marked at early stages ofdevelopment, proconvulsant action of antagonist can be expected inimmature rats.

Method: Rat pups 12 and 25 days old were pretreated with an antagonistof GABAB receptors CGP46381 (1–30 mg/kg intraperitoneally) and 30min later pentetrazol (60 mg/kg subcutaneously) or kainic acid (intraperito-neally - 4 mg/kg in 12- and 6 mg/kg in 25-day-old rats) was injected. Ani-mals were observed in isolation for 30 min and seizures were registered.

Result: Pentetrazol in the dose of 60 mg/kg led exceptionally to convul-sive seizures. CGP46381 potentiated the convulsant effect in 12- but not25-day-old rats. Significant changes were found in the incidence andseverity of seizures in the younger group after the 10- and 30-mg/kg

doses. Kainic acid induced only epileptic automatisms – scratching in 12-and wet dog shakes and scratching in 25-day-old rats. CGP46381 againwas more effective in 12-day-old rats - it increased the intensity and fre-quency of automatisms in a dose-dependent manner - whereas effects in25-day-old animals were mild.

Conclusion: An antagonist of GABAB receptors was active in 12-day-old rats in both models induced by different mechanisms – antagonism ofGABAA receptors (pentetrazol) and antagonism of kainic acid glutamatereceptors. There was no effect on pentetrazol action in 25-day-old ratsand a mild effect on kainic acid-induced automatisms. The role ofGABAB receptors is age- as well as model-dependent. Supported by agrant No. P304/10/1274 of the Grant Agency of the Czech Republic

p594THE ANTIDEPRESSANTS CITALOPRAM AND RE-BOXETINE REDUCE SEIZURE FREQUENCY INCHRONIC EPILEPTIC RATSR. Clinckers, K. Vermoesen, A. Massie, and I. SmoldersVrije Universiteit Brussel, Brussels, Belgium

Purpose: Antidepressants have long been considered to possess procon-vulsant properties. This assumption however remains controversial sinceanticonvulsant effects have been attributed to certain antidepressants.The present study was designed to determine the seizure liability of cita-lopram and reboxetine in the kainic acid-induced post-status epilepticusmodel for temporal lobe epilepsy.

Method: Two months after the induction of status epilepticus, chronicepileptic rats (n=16) were video-EEG monitored during 7 consecutiveweeks. Weeks 1, 3, 5 and 7 served as sham weeks during which the ratsreceived intraperitoneal saline injections for 4 consecutive days, fol-lowed by a 3-day sham washout period during which no injections weregiven. During weeks 2, 4 and 6 rats received intraperitoneal injectionswith either citalopram (5, 10 and 15 mg/kg, once daily, n=8) or reboxe-tine (10, 20 and 30 mg/kg, twice daily, n=8) for 4 days, again followed bya washout period of 3 days. Drugs were administered in a randomlyassigned fixed-dose regimen per week. Each rat served as its own control.The drug doses were selected based on the doses reported to have antide-pressant effects in rats.

Result: Both antidepressants significantly decreased spontaneous sei-zure frequency (15 mg/kg citalopram: 31% decrease; 20 mg/kg reboxe-tine: 44% decrease; 30 mg/kg reboxetine: 39% decrease). Citalopramand reboxetine had no effect on mean seizure severity and seizure dura-tion in any of the doses tested.

Conclusion: In general we conclude that antidepressant doses of cita-lopram and reboxetine have an anticonvulsant effect on spontaneous sei-zures in the kainic acid-induced post-status epilepticus rat model.

p595ANTIEPILEPTIC EFFECT OF TIANEPTINE IN PENTY-LENETETRAZOLE INDUCED SEIZURES IN RATS:POSSIBLE ROLE OF NMDA RECEPTORR. Kh, P. Prabhakar, J. Mehla, and Y. K. GuptaAll India Institute of Medical Sciences, New Delhi, India

Purpose: Depression is a common morbidity in epileptic patients.Adversely, some antidepressants are known to reduce seizure threshold.Tianeptine, an antidepressant drug, has recently been shown to have anti-seizure effect in experimental models. The present study examined theeffect of tianeptine on seizures and its interaction with N-methyl-D-aspartate (NMDA) receptor.

Method: Male Wistar rats (175–225 g) were used. In pentylenetetrazole(PTZ) induced seizure, animals were divided into five groups. The firstgroup received PTZ, 60 mg/kg; i.p. In the second, third and fourth groups,

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tianeptine was administered in three doses of 20, 40 and 80 mg/kg, p.o.,60 min before PTZ injection. In the fifth group, valproate, 300 mg/kg, i.p.was administered as the standard control. In another set of experiments,tianeptine was administered with NMDA 120 mg/kg; i.p., NMDA antag-onist (MK-801, 1 mg/kg; s.c.) with and without PTZ chemoconvulsantchallenge. Behavioural parameters were assessed before and after seizureinduction by using a battery of tests.

Result: Tianeptine exhibited dose-dependent protection against PTZinduced seizures. No generalised tonic clonic seizures were observedwith tianeptine, 80 mg/kg. Tianeptine also showed complete protectionagainst NMDA induced seizures. Co-administration of tianeptine withMK-801 potentiated the anti-convulsant effect of tianeptine suggestinginvolvement of NMDA receptor. Impairment of learning and memorycaused by seizures was reversed by tianeptine.

Conclusion: The protective effect of tianeptine against PTZ andNMDA-induced seizures as well as reversal of cognitive impairment sug-gests the potential of tianeptine in epileptic patients with depression.

p596SUCROSE PREFERENCE TEST REVEALS DEPRES-SION-ASSOCIATED ANHEDONIC BEHAVIOUR IN EPI-LEPTIC MICES. Klein, M. Bankstahl, J. P. Bankstahl, and W. LçscherUniversity of Veterinary Medicine Hannover, Hannover,Germany

Purpose: Depression is a major co-morbidity in epilepsy patients butunderlying mechanisms are poorly understood. Anhedonia, which is acharacteristic symptom of depression in human patients, has been shownto occur also in chronically epileptic rats. This is the first study to investi-gate whether the sucrose preference test can reveal anhedonic behaviourin a mouse model of chronic epilepsy.

Method: Female FVB/N mice were single housed. Baseline wateruptake and preference of either sucrose (4%, group 1) or saccharin (0.1%,group 2) compared to water consumption was quantified. Subsequently,a status epilepticus was induced by fractionated i.p. administration ofpilocarpine. At several time points during epileptogenesis (up to 8 weeksafter status epilepticus) either sucrose or saccharin consumption com-pared to water was measured (further time points are under evaluation).Sham-treated animals served as controls. Additional groups of similarlytreated rats were used as reference.

Result: Baseline water uptake did not differ between groups. Absoluteand relative sucrose or saccharin consumption in post-status-epilepticusmice was significantly decreased at all investigated time points. In epi-leptic rats, however, only absolute sucrose consumption was reproduc-ibly decreased.

Conclusion: Our data provide evidence that the sucrose preference testis suitable to measure anhedonia as an equivalent of epilepsy-associateddepression-like behaviour in mice. We will use this test for further study-ing underlying mechanisms and possible treatments of the co-morbidityof epilepsy and depression in genetically modified mice.

p597MODULATION OF C-FOS AND BDNF PROTEINSEXPRESSION IN PTZ-KINDLED MICE FOLLOWINGTHE TREATMENT WITH NOVEL ANTI-EPILEPTICCOMPOUND 2-ACETYL-3-(2-HEXANOYLAMIDOETH-YL)-7-METHOXYINDOLE: AN IMMUNOHISTOCHEMI-CAL ANALYSISS. M. Malhi*, H. Jawed*, F. Hanif�, N. Ashraf*, S. Farhat*,B. Siddiqui*, S. Begum*, and S. U. Simjee*

*Lab#314, HEJ Research Institute of Chemistry, ICCBS,Karachi, Pakistan; and �Dr. Panjwani Centre for MolecularMedicine and Drug Research, Karachi, Pakistan

Purpose: Epilepsy is a neurological disorder manifested by recurrentseizures, resulting from synchronized discharges of neurons in brain,affecting at least 1% of the world population. The antiepileptic drugsavailable in market have significant side effects and resistance. There-fore, it is logical to search for better and safer newer antiepileptic drugs.In addition, c-Fos and BDNF are the underlining cellular and molecularfactors reported to be tightly coupled with epileptogenesis, therefore wehave focused on these two markers.

Method: Keeping these facts in mind, our group also focused on synthe-sizing a tryptamine derivative, HLL-6, with potential anti-epileptic activ-ity and minimal adverse effects by the help of our chemist collaborators.Pentylenetetrazole (PTZ) was used to induce kindling in mice in ourstudy (n = 12). The immunohistochemical analysis of c-Fos and BDNFproteins in the cryo-sectioned brain slices of both the kindled and normalanimals was performed. The image processing program ImageJ (NIH,USA) was used to analyze the images. Data were obtained from two sec-tions per mouse and presented as means € SEM.

Result: Our results demonstrated that HHL-6 not only possesses potentanticonvulsant and anti-epileptic activity in the PTZ-induced acute sei-zure and chemical kindling model of epilepsy but also shows a markedreduction in the over-expression of c-Fos and BDNF proteins seen in thecontrol kindled group.

Conclusion: Based on our results we suggest that the HHL-6 might beacting as an anti-epileptogenic by controlling the cellular expression ofthe factors that contribute in the development of epileptogenic plasticityin the CNS.

p598TARGETING EPILEPSY: MOLECULAR MARKERS OFEPILEPTOGENESIS AND ITS MODULATION BY ISO-XYLITONES [E/Z ISOMERIC MIXTURE]S. U. Simjee*, M. N. Ashraf*, F. Shaheen*, A. Rahman�,M. I. Choudhary�, N. Kabir�, S. U.A. Shah�, N. Khan*, andS. Jamall§

*International Center for Chemical and Biological Sciences,Karachi, Pakistan; �Karachi, Pakistan; �International Center forChemical and Biological Sciences, University of Karachi,Karachi, Pakistan; and §University of Karachi, Karachi, Pakistan

Purpose: An early immediate gene c-fos has been proposed as the generesponsible for turning on molecular events that might underlie the long-term neural changes occurring during kindling. We have evaluated theeffects of novel anticonvulsant isomeric compound isoxylitones (E/Z) onthe c-Fos expression in the brain samples of kindled mice.

Method: Kindling was induced in NMRI mice by pentylenetetrazole(PTZ) until a seizure score of 4–5 was achieved. The c-Fos expressionwas quantified by immunohistochemistry and RT-PCR protocols.

Result: Immunohistochemical and RT-PCR analysis revealed a markedincrease in the expression of c-fos in the brain regions in case of PTZ-kin-dled control group compared to normal control. In comparison to PTZ-control group, the isoxylitones (30 mg/kg)-treated group demonstratedsignificant reduction of c-Fos expression. However, low expression of c-fos mRNA was only detected in the thalamus of the isoxylitone-treatedbrain samples.

Conclusion: Based on these observations, we suggest that isoxylitonesmay have the capacity to control the seizure pattern by mechanism suchas the suppression of c-Fos protein and mRNA levels in different regionsof the brain. Further investigations to explore the mechanism of action ofthese compounds are under process.

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p599CENTRAL AND OBSTRUCTIVE APNEA AND CARDIACARRHYTHMIA DURING SEIZURES ALL PLAY ROLESIN SUDDEN DEATH IN A DRAVET SYNDROME MOUSEMODELY. Horigome*, M. Iizuka�, I. Ogiwara�, T. Shinba*, andY. Takahashi**National Epilepsy Center, Shizuoka Institute of Epilepsy andNeurological Disorders, Shizuoka, Japan; �Ibaraki PrefecturalUniversity of Health Sciences, Ami, Japan; and �RIKEN BrainScience Institute, Wako, Japan

Purpose: Sudden unexpected death in epilepsy (SUDEP) is a tragicevent to be avoided but the mechanisms still remain unclear. Patientswith Dravet syndrome (DS) with SCN1A gene mutations show extremelyhigh incidence of SUDEP. The DS mouse model harboring a heterozy-gous Scn1a mutation (R1407X; RX/+) also exhibits very high mortalityrate, and 40% die before postnatal day (P) 90. To elucidate the mecha-nisms of SUDEP, we performed simultaneous recordings of respiration/ECG/EEG in RX/+ mice.

Method: The respiration during spontaneous seizures was monitored bywhole-body plethysmograph in 31 RX/+ mice. Simultaneous ECG/EEG/respiration recordings were also performed when feasible. Seizures wererecorded in all the experiments by video. Preventive effects of mechani-cal ventilation and oxygen pretreatment against death were evaluated inpentylenetetrazol-induced seizures (150mg/kg i.p.) in RX/+ mice.

Result: In younger pups (P17–22, n=11), seizures with small jumps(popcorn seizures) clustered and they were not lethal. From P21, jumpingseizures followed by tonic hindlimb extension appeared (n=10), resultingin sudden respiratory arrest and sudden death in four (P23, 24, 24, 86). Inthe other six mice, respiration resumed after 12–42 sec apnea. Gaspingwas clearly observed after central apnea, indicating coexistence of upperairway obstruction. Various types of cardiac arrhythmia appeared duringseizures, including profound bradyarrhythmia (70–80% reduction ofheart rate), ventricular tachycardia and torsade-like ST-T wave changes.

Conclusion: The present study showed that ictal deaths were caused bysudden central and subsequent obstructive apnea after generalized jump-ing seizures. Cardiac arrhythmias might also be implicated in the mecha-nism.

p600TRANSPLANTATION OF EMBRYONIC STEM CELLSTO DORSAL HIPPOCAMPUS OF EPILEPTIC MUTANTEL MICEY. L. MurashimaTokyo Metropolitan University Graduateschool of HumanHealth Science, Tokyo, Japan

Purpose: Pluripotent embryonic stem (ES) cells differentiate into neu-rons in vitro. This is the key in the study of neurogenesis and in the gener-ation of donor cells for neuronal transplantation. Cultured in astrocyte-conditioned medium (ACM), colonies of undifferentiated mouse ES cellsgive rise to floating spheres of concentric stratiform structure with aperiphery of neural stem cells: Neural Stem Spheres (NSS). Culturing thespheres on an adhesive substrate in ACM promotes neurogenesis. ELmice show secondary generalized seizures, which initiate at the parietalcortex and generalize through the hippocampus. The purpose of the pres-ent study was to examine how transplanted neural stem cells (NSCs) dif-ferentiate into inhibitory neurons and play a role of anti-epileptic effectsin EL mice.

Method: Neuron-induced NSCs (nNSCs), GABAergic neuron-inducedNSCs (gNSCs) after 24hrs incubation from NSCs originated from NSSwere used for the transplantation. 1 · 104 cells were transplanted to both

sides of dorsal hippocampus. Five weeks after, it was checked whetherseizures were controlled or not, and then, brains were analyzed byimmunohistochemistry using GFP, GAD, and Neu-N.

Result: In EL, gNSCs transplanted group showed no seizure at all,whereas vehicle control showed seizures. GAD positive transplanted(GFP positive) neurons (NeuN positive) were observed more clearly inthe GABAergic group, compared with those of neuron-induced group.

Conclusion: Inhibitory differentiated gNCSs transplanted mice showedGAD positive cells more remarkably than those of nNCSs transplantedmice. In EL, the hippocamous and the parietal cortex may have a capacityfor inhibitory neurons to control seizures.

p601C-FOS EXPRESSION AFTER HIPPOCAMPAL DEEPBRAIN STIMULATION IN RATSJ. Silva, M. Marques, F. Scorza, E. Cavalheiro, and A. CukiertUNIFESP, Sao Paulo, Brazil

Purpose: Hippocampal deep brain stimulation (Hip-DBS) is a promis-ing technique for treatment of patients with refractory temporal lobe epi-lepsy not amenable for conventional resective surgery. On the otherhand, little is known about its effect on normal or pathological brainactivity. We describe the expression of c-FOS after Hip-DBS in rats.

Method: Six awaken male Wistar rats implanted bilaterally with neo-cortical and hippocampal electrodes and 2 control (non-stimulated) ani-mals were studied. The animals were submitted to 1 hour or 6 hours ofunilateral continuous hippocampal high frequency (130Hz) stimulation.Immunohistochemistry was employed to visualize c-fos distribution indifferent brain areas. Tissue sections were mounted on glass slides. Thematerial was studied with a microscope using bright-field illumination.

Result: c-FOS was significantly overexpressed bilaterally (althoughprevailing ipsilaterally) after unilateral Hip-DBS in regions comprisingthe hippocampus, pyriform gyrus, amygdala, olfactory nuclei, anteriornucleus of the thalamus and mammilary body, and less markedly over thecingulate cortex. No other thalamic or brain stem nuclei were shown tooverexpress c-FOS.

Conclusion: Unilateral Hip-DBS was able to affect all the basic relaysof the limbic system and could potentially modulate that system bilater-ally. This contrasts with recent findings showing that anterior nucleusstimulation led to very weak c-FOS activation of the hippocampus, sug-gesting that Hip-DBS might be a better target for limbic system neuro-modulation. FAPESP, CInAPCe-FAPESP, CNPq and FAPESP/CNPq/MCT-Instituto Nacional de NeurociÞncia Translacional.


p602HIGH FREQUENCY HIPPOCAMPAL DEEP BRAINSTIMULATION (HIP-DBS) DID NOT ENHANCEINFLAMMATORY MEDIATORS IN THE RAT HIPPO-CAMPUSS. Perosa, J. Silva, F. Scorza, E. Cavalheiro, M. Naffah-Mazzacoratti, and A. CukiertUNIFESP, Sao Paulo, Brazil

Purpose: There are clinical and experimental evidence that suggest thatinflammatory mediators and processes could modulate epileptogenesis.

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DBS has been increasingly used in the treatment of refractory epilepsy.In this study, we investigated if Hip-DBS influenced inflammatory medi-ators in the rat.

Method: Six awaken male Wistar rats implanted bilaterally with neo-cortical and hippocampal electrodes and 2 control (non-stimulated)animals were studied. The animals were submitted to 1 hour or 6hours of unilateral continuous hippocampal high frequency (130Hz)stimulation. Immunohistochemistry was employed to visualize anti-bradykinin B1 receptor, anti-bradykinin B2 receptor, TNF|� and IL1|ffin the hippocampal formation. Tissue sections were mounted on glassslides. The material was studied with a microscope using bright-fieldillumination.

Result: There was no difference in the expression of any of the studiedinflammatory mediators in the hippocampus of the rat after Hip-DBS.

Conclusion: The mechanisms through which Hip-DBS might lead to ananticonvulsant effect are poorly understood. This type of neuromodula-tion, which triggers intense c-FOS activation within the whole limbic sys-tem, did not cause overexpression of inflammatory mediators.Inflammatory pathways might not be involved in the cascades leading toseizure frequency reduction after Hip-DBS. FAPESP, CInAPCe-FA-PESP, CNPq and FAPESP/CNPq/MCT-Instituto Nacional de NeurociÞn-cia Translacional.

p603THE EFFECT OF HIGH FREQUENCY, POISSON DIS-TRIBUTED CORTICAL STIMULATION ON CORTICALEXCITABILITY IN RATSI. Buffel*, A. Meurs*, R. Raedt�, V. De Herdt*, R. El Tahry*,B. Van Nieuwenhuyse*, L. Mollet*, W. Wytse�, K. Vonck*, andP. A. J. M. Boon**University Ghent, Ghent, Belgium; �Ghent University, Ghent,Belgium; and �Swammerdam Institute of Life Sciences,Amsterdam, The Netherlands

Purpose: Neurostimulation is a promising treatment for patients withrefractory focal epilepsy who are not amenable to resective surgery. Wehave evaluated the effect of high-frequency cortical stimulation on corti-cal excitability in the motor cortex model (CSM). In the CSM, a ramp-shaped pulse train with increasing intensity is delivered to the motor cor-tex. The threshold intensity for eliciting forelimb clonus is determinedthrough behavioural observation, and used as a measure for cortical excit-ability.

Method: Seven male Wistar rats were implanted with epidural elec-trodes over the motor cortex (AP-1mm; ML€3mm). All rats underwent1h of sham stimulation, cortical stimulation (Poisson pulse, 130Hz,PW100ls) with an intensity of 10lA, or cortical stimulation at 100lAbelow the baseline threshold intensity on alternating days. The thresholdintensity needed to elicit forelimb clonus was determined before (meanof 4measurements at 20min intervals) and immediately, 1h, 2h and 24hafter stimulation.

Result: Sham stimulation did not alter the threshold to forelimb clonus.Therapeutic stimulation with an intensity of 100lA lower than baselinethreshold (mean intensity 205€22lA) significantly increased the thresh-old to forelimb clonus from 305€22lA (before) to 347€19 (immediatelyafter), 339€23 (1h), 327€20 (2h) and 277€21lA (24h) after stimulation(p<0.001). When stimulated at 10lA, the threshold increased from302€25lA to 319€15lA, 318€21lA, 319€18 lA, 321€32lA.

Conclusion: High-frequency, Poisson-distributed cortical stimulationdecreases cortical excitability at high intensities. This effect lasted 1h.Further studies are needed to determine whether this type of stimulationcan become an effective alternative treatment for patients with focal neo-cortical epilepsy who are not amenable to surgery.

p604ARE ASTROCYTES INVOLVED IN THE EPILEPTO-GENESIS?. THE EFFECTS OF THROMBOSPONDINRECEPTOR BLOCKAGE IN A MODEL TEMPORALLOBE EPILEPSYA. J. Ramos, A. Rossi, M. F. Angelo, A. Villarreal, J. Lukin, andA. G. ReinesSchool of Medicine, University of Buenos Aires, Ciudad deBuenos Aires, Argentina

Purpose: Reactive astrocytes are known to secrete thrombospondins(TSP) that are specifically involved in the glutamatergic synaptogenesis.During the latency neuronal network reorganization is supposed to be thesubstrate for the epileptogenesis. In this study we evaluated if astrocytesand TSP are involved in the exacerbated neuronal plasticity that occursduring the latency period that precedes the final appearance of spontane-ous recurrent seizures.

Method: Using loss of function studies achieved by blocking the neuro-nal thrombospondin receptor alpha2delta1 with gabapentin (Gp) in ratsexposed to the Lithium-pilocarpine model of temporal lobe epilepsy, wefollowed the changes in neuronal circuits and reactive gliosis. Adult maleWistar rats were treated with 3mEq/kg LiCl and 20h later with 30mg/kgpilocarpine (ip). 15 minutes after the onset of the status epilepticus (SE),they received 10mg/Kg diazepam. For the next 15 days animals received400 mg/kg/day Gp or saline. In vitro, glio-neuronal hippocampal cultureswere exposed to excitotoxic glutamate and subsequently to Gp (5, 25, 50or 100 ug/ml) or vehicle.

Result: During the latency, SE animals showed reactive gliosis, neuro-nal degeneration, ultrastructural alterations in synapses with atypicalexpression of synaptofisin (Syn) and increased level of plasticity markerPSA-NCAM in the hippocampus. Gp treatment reduced the alterations inSyn and PSA-NCAM but was unable to modify the neuronal loss andreactive gliosis. In glio-neuronal culture, Gp treatment partially pre-vented the dendritic loss caused by glutamate.

Conclusion: The atypical synaptic morphology is probably related tothe exacerbated neuronal plasticity and blockage of neuronal TSP recep-tor partially prevented this effect

p605IDENTIFICATION OF KINASE INHIBITORS THATPROTECT AGAINST SEIZURES IN ZEBRAFISH ANDRODENT MODELS OF EPILEPSYN. Aourz*, A. Serruys�, J. N. Chabwine�, P. B. Balegamire�,T. Afrikanova�, R. Edrada-Ebel§, A. Grey§, A. R. Kamuhabwa–,L. Walrave*, R. Clinckers*, C. V. Esguerra�, P. A. M. De Witte�,I. J. Smolders*, and A. Crawford�

*Vrije Universiteit Brussel, Brussels, Belgium; �Leuven,Belgium; �Bukavu, Congo; §Scotland, UK; and –Dar es Salaam,Tanzania

Purpose: In view of the clinical need for new anti-epileptic drugs(AEDs) with novel modes of action, we used a zebrafish seizuremodel to screen the anticonvulant activity of medicinal plants usedfor traditional epilepsy treatment in the Congo, identifying 4 crudeplant extracts that inhibited pentylenetetrazol (PTZ)-induced seizuresin zebrafish larvae. Bioassay-guided fractionation of an anticonvulsantFabaceae species identified an alkaloid with known kinase inhibitoryactivity***. This compound, a more potent and specific structuralanalog, and a structurally unrelated kinase inhibitor were analyzed inzebrafish and rodent seizure assays. ***For intellectual property rea-sons, the identity of the plant species, compounds and kinase targetwill first be revealed at the 10th European Congress on Epileptologyin London.

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Method: Locomotor activity of PTZ- and pilocarpine-treated zebrafishlarvae was quantified by automated video tracking (Viewpoint). Seizureswere induced in NMRI mice by corneal stimulation (6Hz, 0.2 ms rectan-gular pulse width, 3s duration) and in Wistar rats by intrahippocampalpilocarpine perfusion (12 mM, 40 min), and quantified.

Result: All 3 compounds revealed anticonvulsant activity in PTZ- andpilocarpine-treated zebrafish larvae, with EEG recordings revealingreduction of epileptiform discharges. All 3 compounds showed anticon-vulsant activity in the pilocarpine rat model for limbic seizures and the6Hz psychomotor seizure mouse model for partial epilepsy. Antisenseknockdown of the target kinase in zebrafish partially protected larvaefrom PTZ-induced seizures. Kinase overexpression experiments in ze-brafish and mice are ongoing.

Conclusion: These results suggest possible strategies for the discoveryof new AEDs with novel mechanisms of action.

p606ELECTROGRAPHIC BUT NOT BEHAVIOURAL MEA-SURES OF EPILEPTIC ACTIVITY ARE RELIABLEINDICATORS OF THE EFFICACY OF KETOGENICDIET IN PENTYLENETETRAZOL ACUTE SEIZUREMODELD. She, I. Kharatishvili, and D. ReutensCentre for Advanced Imaging, Brisbane, Qld, Australia

Purpose: Ketogenic diet (KD) is a high-fat low carbohydrate diet thatexerts antiepileptic properties. Here, we performed electrographic quan-tification of the efficacy of KD on PTZ-induced seizures and compared itwith commonly used observational outcome measures.

Method: Epidural electrodes were implanted into 4 week-old maleSprague-Dawley rats bilaterally. Animals were then divided in 2 weight-matched groups and fed ad libitum either standard diet (STD, n=8) or KD(n=7), respectively (Specialty Feeds, WA, Australia), for 21 days. Afterthat, acute seizures were induced under video-EEG control by continuousinfusion of pentylenetetrazol (PTZ, 20 mg/ml, 0.1ml/min infusion rate)through the tail vein. Interictal and ictal behavioural and electrographicpatterns were quantified and compared between the groups.

Result: KD group had a lower number of interictal spikes (p=0.02),lower spike frequency (p=0.029) and spent less time in seizure (a percent-age of time from beginning of infusion to tonic seizure, p=0.045, Mann-Whitney U). No significant difference in seizure duration was observedbetween the KD group and the STD group. The latency times and thethreshold dose of PTZ to first overt myoclonic twitch, first spike, first clo-nic or first tonic seizure did not differ significantly between the groups.

Conclusion: Our data suggest that quantification of electrographic ictaland interictal epileptiform activity can assess anticonvulsant propertiesof KD more reliably than commonly used outcome measures based onbehavioral seizure characteristics.

p607BLOOD-BRAIN BARRIER INTEGRITY AND PENTY-LENETETRAZOLE-INDUCED SEIZURE SEVERITY INSEPTIC RATSM. B. Bahceci, N. Orhan, B. Ahishali, N. Arıcan, C. Ugur,C. Gurses, and M. KayaIstanbul University, Istanbul, Turkey

Purpose: The impact of seizures that emerge under a systemic inflam-matory background in sepsis on the functional and morphological fea-tures of blood-brain barrier (BBB) is not fully understood. In the currentstudy we investigated the effects of pentylenetetrazole (PTZ)-induced

seizures on BBB integrity in an experimental model of sepsis induced bycecal ligation and puncture (CLP) in rats.

Method: Wistar rats were divided into control, CLP, PTZ and CLP plusPTZ groups. PTZ was administered to induce seizures and EEG wasrecorded. BBB permeability was assessed by measurement of Evans blue(EB) in the brain tissue. Immunohistochemistry was performed for occlu-din, p-glycoprotein (p-gp) and aquaporin (AQP)-4 proteins.

Result: Arterial blood pressure decreased and rectal temperatureincreased in septic animals (P<0.05). The severity and duration of PTZ-induced seizures were found to be increased in septic animals comparedwith intact animals. Immunoreactivity for p-gp increased in PTZ andCLP plus PTZ groups compared with CLP operated animals and controls(P<0.05). Immunostaining for AQP-4 was most intense in CLP operatedrats compared with CLP plus PTZ and control groups (P<0.01).

Conclusion: The results of this study show that sepsis enhances PTZ-induced seizure severity and the degree of BBB disruption in rats. Wesuggest that alleviating the functioning mechanistic processes in sepsismay reduce the damage to barrier-type endothelial cells in seizures underseptic conditions.

p608VARIOUS KINDS OF HYPERPOLARIZING AFTERPO-TENTIALS IN NEOCORTICAL NEURONS DURING EPI-LEPTIC DISCHARGESV. Tsomaia, V. Okujava, T. Labakhua, S. Chipashvili,L. Mestvirishvili, and G. KvernadzeIv. Beritashvili Centre Experimental Biomedicine, Tbilisi,Georgia

Purpose: The objective of presents investigation was the elucidation ofintimate inhibitory mechanisms in cortical neurons leading to the arrestof epileptic ictal activity.

Method: Experiments were performed on adult cats. Ictal activity wasinduced by repetitive electrical stimulation of the cerebral cortex. Intra-cellular microelectrodes were used for recording the neuronal electricalactivity. The same electrodes were used for measuring the electricalparameters of the neuronal membrane (resistance) and for intracellularinjection of specific compounds.

Result: It has been established that prolonged hyperpolarization, whichappears at the end of ictal discharges and which conditioned their arrest,should be induced by dual mechanism. On the one hand, it must be theresult of the common mode of central inhibition produced by conduc-tance inhibitory postsynaptic potentials (conductance IPSP) caused by anincreased permeability of the membrane to chloride or potassium ions orto the both. On the other hand, the longer part of this hyperpolarizationduring which themembrane resistance is not charged, must be the resultof the activation of the electrogenic pump, as revealed in experimentswith intracellular injection of Vanadate which blocks the pump.

Conclusion: In conclusoin one may suggest that during epileptiform dis-charges in neocortical neurons of the cat hyperpolarizing afterpotentialswhich follow PDS are of a composite nature and include three differentcomponents partially overlapping each other and forming one prolonged(sometimes undulating) deflection of membrane potential.

p609EFFECT OF MILD HYPOTHERMIA ON GLUTAMATERECEPTOR EXPRESSION AFTER STATUS EPILEPTI-CUSL. Yu, and Y. WangChildren's Hospital of Fudan University, Shanghai, China

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Purpose: Hypothermia has been shown to have neuroprotective effectsin various models of neurological damage. However, its therapeuticeffect on pediatric status epilepticus (SE) is still unknown. We conducteda study to investigate whether hypothermia can have an adjuvant effecton pilocarpine-induced status epilepticus in immature rats when com-bined with diazepam treatment.

Method: SE were induced by pilocarpine on 21-day-old Wistar rats,which was followed by injection with diazepam and/or treatment withmild hypothermia. Rats were recorded with ECoG before and after SE. Inaddition, we analyze the necrosis and apoptosis of the neurons anddetected the expression of GluR1, GluR2 and mGluR1 after SE throughimmunohistochemistry and Western blot in each group. We also calcu-lated glutamate receptor mRNA in PCR.

Result: We found that the spike-wave amplitude and frequency after SEduring treatment with diazepam and hypothermia was significantly lowerthan treatment with diazepam alone. Mild hypothermia significantlyreduced the number of cells undergoing necrosis and apoptosis. In addi-tion, GluR1 was shown to be up-regulated by SE, while GluR2 wasshown to be down-regulated. However, after combination therapy withdiazepam and mild hypothermia for 8 hours, the expression of GluR1was decreased and GluR2 was increased relative to the levels of diaze-pam alone treated juveniles. We also found that the expression ofmGluR-1a was also decreased relative to diazepam alone.

Conclusion: These findings suggest that mild hypothermia might fur-ther protect against pilocarpine-induced status epilepticus in immaturerats by regulating glutamate receptor expression.

p610EPILEPSY-DEPENDENT ARCHITECTURAL ANDNMDA ABNORMALITIES IN MAM-PILOCARPINE RATBRAINF. Colciaghi*, A. Finardi*, P. Nobili*, G. Spigolon�,A. Vezzani�, and G. Battaglia**IRCCS Neurological Institute Carlo Besta, Milano, Italy;�University of Torino, Torino, Italy; and �Mario Negri Institutefor Pharmacological Research, Milano, Italy

Purpose: We have recently demonstrated that the occurrence of statusepilepticus (SE) and subsequent seizures in malformed rat brain, i.e., themethylazoxymethanol-pilocarpine treated rat (MAM-PILO; Colciaghi F.Brain, 2011;134:2828–43) beget a pathologic process capable of modify-ing the morphology of pyramidal neurons and NMDA receptor expres-sion/localization. Here we have verified whether the extent of theobserved abnormalities might be related with epilepsy duration.

Method: Epileptic MAM-PILO rats were analyzed respectively 3–5days (early chronic stage -EC) and 3–6 months (chronic stage) after epi-lepsy onset. Spontaneous recurrent seizures were quantified with video-EEG-monitoring. MAM rats not experiencing SE were used as controls(MAM/noSE). In all rat groups we performed morphologic and molecu-lar analysis.

Result: Morphometric analysis of thionine-stained sections showed anepilepsy-dependent cortical thinning progression (20% and 35% after 3and 6 months of epilepsy vs MAM/noSE rats) and decrease of hippocam-pal volume (45% and 60% after 3 and 6 months vs MAM/noSE). No dif-ferences were obtained between MAM-PILO EC and MAM/noSE rats.Further, we observed a time-dependent increase of dysmorphic neuronswith neurofilament and NMDA over-expression (EC vs 3 months epi-lepsy, *p<0.05; EC vs 6 months epilepsy, ***p<0.001; 3 vs 6 months epi-lepsy, **p<0.01) and a significant hyperphosphorylation of NMDA-NR2B subunit associated with both malformed cortex and hippocampusof epileptic MAM compared to MAM/noSE brain.

Conclusion: Our data indicate that in MAM-PILO rats the extent ofstructural and NMDA abnormalities of cortical pyramidal neurons are

positively related to epilepsy duration and suggest that targeting NMDAreceptors may affect the course and severity of epilepsy.

p611INACTIVATION OF THE CONSTITUTIVELY ACTIVEGHRELIN RECEPTOR ATTENUATES LIMBIC SEI-ZURE ACTIVITY IN RODENTSJ. Portelli*, L. Thielemans�, L. Ver Donck�, E. Loyens*,J. Coppens*, N. Aourz*, J. Aerssens�, K. Vermoesen*,R. Clinckers*, A. Schallier*, Y. Michotte*, D. Moechars�,G. L. Collingridge�, Z. A. Bortolotto�, and I. Smolders**Vrije Universiteit Brussel, Brussels, Belgium; �JanssenPharmaceutica, Beerse, Belgium; and �University of Bristol,Bristol, UK

Purpose: Ghrelin is a pleiotropic neuropeptide that has recently beenimplicated in epilepsy, however its mechanism of anticonvulsant actionis unknown.

Method: In this study we used the in vivo rat model for pilocarpine-induced limbic seizures, the mouse pilocarpine tail infusion model, trans-genic mice with a growth hormone secretagogue receptor (GHSR) dele-tion, electrophysiology in hippocampal slices, EEG recording in freelymoving rats, and HEK293 cells expressing the human GHSR to deter-mine inverse agonism, activation, desensitization, internalization and re-sensitization.

Result: Ghrelin and the ghrelin-mimetic capromorelin attenuated pilo-carpine-induced seizures in rats and mice. Experiments with transgenicmice ascertained that ghrelin requires the GHSR for its anticonvulsanteffect. Unexpectedly we found that GHSR-/- mice had a higher seizurethreshold than GHSR+/+ mice when treated with pilocarpine. This obser-vation prompted us to look further into pharmacological modulation ofthe receptor. We discovered that abolishing the constitutive activity ofGHSR by inverse agonism results in the attenuation of seizures and epi-leptiform activity. We confirmed that ghrelin's potential to rapidly desen-sitize the GHSR is followed by internalization of the receptor and a slowresensitization process. This, together with our present novel findingsthat different ghrelin fragments possess similar agonistic potencies butdifferent desensitization characteristics on the GHSR, led us to elucidatethat ghrelin probably attenuated limbic seizures in rodents and epilepti-form activity in hippocampal slices due to its desensitizing effect on theGHSR.

Conclusion: To the best of our knowledge, this constitutes a novelmechanism of anticonvulsant action whereby an endogenous agonistreduces the activity of a constitutively active receptor.


p612EFFECTS OF N-METHYL-D-ASPARTIC ACID-INDUCED SPASMS ON THE BRAIN: IN VIVO MAG-NETIC RESONANCE SPECTROSCOPYM. Yum*, D. W. Kim�, S. Kim*, L. Velisek�, B. S. Lee*, andT. Ko**Asan Medical Center, Seoul, Korea; �Ilsan Paik Hospital, InjeUniversity College of Medicine, Goyang; and �New YorkMedical College, New York, NY, USA

Purpose: Infantile spasms are notorious for causing severe cognitiveproblems in children, even without detectable brain lesions. However,

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the mechanisms of this catastrophic outcome are still unknown. We havedeveloped animal models of infantile spasms and investigated the patho-physiology of infantile spasms. The aim of this study is to show the con-sequences of the NMDA-induced spasms in a rat model by in vivoanalysis of magnetic resonance spectroscopy.

Method: To compare the effects of multiple bouts of spasms on devel-oping rat brains, prenatally betamethasone-exposed pups were subjectedto 3 times of intraperitoneal NMDA-induced spasms (n=9) or salineinjections (controls, n=9) on postnatal days 12, 13, and 15. 1H-magneticresonance spectroscopy with ROI of cortex and basal ganglia(3x3x3mm3) and T2-weighted MRI, 24hr after the single and multiplespasms and at 7, 21, 35 days after last NMDA-induced spasms, wereobtained. Linear mixed model was used for statistical analysis

Result: There was no significant gross morphological difference onserial MRI between groups. Choline in basal ganglia and N-acetyl aspar-tate, choline, lipid-plus-lactate at 1.3 ppm in cortex showed significantchanges by time (p<0.05). Only choline in basal ganglia showed signifi-cant decrease after spasms compared to controls (p=0.009).

Conclusion: Despite the absence of structural abnormalities, NMDA-induced spasms result in a time and a region specific change of the metab-olite pattern in the developing rat brain. Further histopathological andelectrophysiological studies are needed to determine exact mechanismsof these changes.

p613SEIZURE ACTIVITY GENERATES CALCIUM-INDE-PENDENT REACTIVE OXYGEN SPECIES VIA NADPHOXIDASE AND XANTHINE OXIDASES. Kovac*, N. Hamil*, S. Williams*, A. Domijan�,M. C. Walker*, and A. Y. Abramov�

*Department of Clinical and Experimental Epilepsy, London,UK; �University of Zagreb, Zagreb, Croatia; and �ION, London,UK

Purpose: Seizure activity has been proposed to result in the generationof reactive oxygen species (ROS), which then contribute to seizure-induced neuronal damage, cognitive dysfunction and further seizures.Seizure-induced production of ROS has been hypothesised to be due tocalcium-dependent mitochondrial dysfunction.

Method: We tested this hypothesis using fluorescence imaging tech-niques in rat glio-neuronal neocortical co-cultures using low magnesiumto induce seizure-like activity and in ex vivo slices from chronically epi-leptic rats using confocal microscopy.

Result: We found that prolonged seizure activity increases neuronalROS production both in vitro and in vivo, and that ROS production invivo is elevated during periods of spontaneous brief seizure-like activity.ROS production in vivo is brain-region specific with a higher rate of ROSproduction in CA1 compared to that in entorhinal cortex. The magnitudeof ROS production in vivo is dependent on the duration of epilepsy.Increases in ROS in epileptic animals translated to a decrease in the majorantioxidant glutathione measured in ex vivo slices. Seizure-induced ROSproduction was NMDA receptor-dependent and occurred alongside oscil-latory calcium signals and a steady intracellular sodium increase in neu-ronal co-cultures. Unexpectedly, however, the production of seizure-induced ROS is not dependent upon mitochondrial dysfunction but isgenerated in a calcium-independent fashion initially through NADPHoxidase and later through xanthine oxidase activity. Consequently, inhi-bition of either of these enzymes reduced seizure-induced neuronal celldeath.

Conclusion: These findings demonstrate a critical role for calcium-independent ROS sources in seizure-induced neuronal death, and providenovel neuroprotective approaches.

p614THE EFFICACY OF INTRAVENOUS VALPROATECOMPARED TO INTRAVENOUS PHENOBARBITAL INCONTROLLING SEIZURES AMONG PEDIATRICPATIENTS WITH BENZODIAZEPINE- REFRACTORYSTATUS EPILEPTICUS: A RANDOMIZED CON-TROLLED TRIALL. K. F. Banta- Banzali, P. D. P. Obligar, J. R. Panlilio, andP. M. D. PascoPhilippine Children's Medical Center, Quezon City, Philippines

Purpose: To determine the efficacy and safety of intravenous valproatecompared to intravenous Phenobarbital in controlling seizures amongpediatric patients with benzodiazepine- refractory status epilepticus.

Method: Status epilepticus patients two to 18 years of age were ran-domly divided into groups A and B and received 20 mg/kg loading doseof intravenous Phenobarbital and intravenous valproic acid, respectively.They were followed up for 24 hours for seizure outcome and adverseevents. They were switched over to the other group if seizures were notcontrolled within one hour or there was seizure recurrence within 12hours of treatment.

Result: The duration of the status epilepticus at the time of presentationwas <2 hours in all patients in Group A and in 82% of patients in Group B.All subjects in the two groups had good outcomes of treatment: seizurewas controlled, no one left against medical advice and there was no mor-tality. Seizure recurrence was mainly seen during the first 12 hours in bothstudy groups. There was no recurrence noted after 12 hours. Intravenousvalproic acid and phenobarbital infusions were well tolerated. Elevationof SGPT was the most common adverse effect seen but the difference inproportion was not statistically significant between the two groups.

Conclusion: Intravenous valproic acid is as effective and just as safe asintravenous phenobarbital as a second line non- sedative anti- convulsantfor pediatric patients with status epilepticus who failed to respond tobolus doses of diazepam.

p615REFRACTORY STATUS EPILEPTICUS IN CHILDREN:LACOSAMIDE EFFICACY AND SAFETYS. Grosso*, N. Zamponi�, E. Cesaroni�, S. Cappanera�,A. Verrotti§, S. Nanni*, R. D. Bartolo*, and P. Balestri**Policlinico S. Maria le Scotte, Siena, Italy; �Ospedali Riuniti-Salesi, Ancona, Italy; �Ospedali Riuniti of Ancona, Ancona,Italy; and §University of Chieti, Chieti, Italy

Purpose: Status epilepticus is a life-threatening neurologic emergencywhich needs a prompt therapeutic approach. When the first and second-line AEDs are ineffective to control SE, it is referred to as refractory SE(RSE). Lacosamide (LCM) was approved as an adjunct AED for partial-onset seizures. It has unique mechanism of modulating voltage-gatedsodium channels by enhancing their slow inactivation. To date, there areanecdotal reports of LCM use in RSE.

To report on the experience with IV Lacosamide in children withRSE.

Method: Pharmacy records were reviewed to identify patients with RSEwho received IV LCM in our institutions. Data on demographics,response to therapy and adverse effects/outcomes were analyzed. Allpatients had continuous EEG monitoring.

Result: 10 children (4 boys), age 3–16 years with RSE were given LCM.Four patients were in generalized non-convulsive RSE, 6 patients were ingeneralized convulsive RSE. The etiologies included idiopathic, cerebralpalsy, neuronal migration disorders, and posterior reversible encephalopa-thy syndrome (PRES). IV LCM was added after traditional AEDs failed to

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control the SE. RSE ceased in 6/10 patients whereas a partial response withcessation of NCSE but still frequent electrographic seizures were noted inanother two. No effects were observed in the remaining two children.

Conclusion: LCM is a useful adjunct in children with RSE. The IV for-mulation allows prompt administration in the intensive care unit setting.The drug demonstrated to be safe. Although larger controlled studies areneeded, IV LCM seems to be a valid therapeutic option in children withRSE.

p616STIMULUS-INDUCED ICTAL EEG PATTERNS INCOMATOSE AND NON-COMATOSE ADULT PATIENTSWITH NONCONVULSIVE STATUS EPILEPTICUSS. Marca, G. Kuester, C. Lobos, C. Quiroz, R. Tapia, andM. ValenciaClinica Las Condes, Santiago, Chile

Purpose: To describe etiologies, morphology, localization, clinicalfindings, and correlation with spontaneous ictal patterns in comatose ornon-comatose adults with nonconvulsive status epilepticus (NCSE) hav-ing ictal phenomena induced by alerting stimuli (SIRPIDs).

Method: We retrospectively reviewed all consecutive prolonged/con-tinuous EEG monitoring done between June 2009 and December 2011.We selected all comatose or non-comatose inpatients with electrographicor electroclinical findings consistent with NCSE having also ictal SIR-PIDs during tactile, photic, auditory, or painful stimuli. We revieweddemographic and clinical features, etiology, morphology and localizationof spontaneous and induced ictal patterns.

Result: 26 patients were selected, 15 male; mean age: 55.3 yo (range:19–91). Most frequent etiologies were intracranial hemorrhage (sixpatients), previous or recent brain infarct (five patients), and severe headtrauma (five patients). Most frequent induced ictal EEG pattern was focalrhythmic activity. Only three patients had clinical changes during ictalSIRPIDs. Location and morphology correlation with spontaneous ictalpatterns was very high.

Conclusion: Induced ictal EEG patterns in NCSE occur in different neu-rological conditions. More frequently they are focal and rhythmic, andvery occasionally they are associated to clinical changes. They have verygood correlation with spontaneous ictal patterns in terms of morphologyand location. They are probably under-diagnosed if stimulus protocolsare not consistently applied in comatose or non-comatose patients withNCSE. They should be identified and possibly require treatment, at leastone preventive intervention.

p617INTRAVENOUS SODIUM VALPROATE FOR STATUSEPILEPTICUSY. Wu, X. Liu, Z. Chen, M. Ma, and S. LiThe First Affiliated Hospital, Guangxi Medical University,Nanning, China

Purpose: To determine whether intravenous sodium valproate was moreeffective or safer than other drugs in patients with status epilepticus, weperformed a meta-analysis.

Method: A literature search was performed using Medline, Embase, theCochrane Central Register of Controlled Trials CENTRAL. From 544articles screened, 5 were identified as randomized controlled trials andwere included for data extraction. Main outcomes were SE controlled,risk of seizure continuation. The meta-analysis was performed with theRandom-effect model. The quality of the included studies was evaluatedby Grade software.

Result: Five studies with 364 participants met the inclusion criteria.There was no statistically signiﬁ cance in SE controlled betweenIntravenous sodium valproate and Phenytoin (110/134 vs. 78/108 partici-pants; RR 1.07 95% CI 0.91, 1.24). Compared with diazepam, sodiumvalproate had a statistically significant lower risk of time interval for con-trol of RSE after giving drugs (8.8 ¡ 7.4/20 vs. 26.6 ¡ 26.7 participants;MD -17.80, 95% CI -29.94, -5.66), however, there was no statisticallysignificant difference in SE controlled within30 minutes between the twogroups (16/20 vs. 17/20 participants; OR 0.71, 95% CI 0.14, 3.66). Therewas no statistically significant difference in cessation from statusbetween Intravenous sodium valproate and Levetiracetam (26/41 vs. 28/41 participants; OR 0.80, 95% CI 0.32, 2.01). Conclusions Intravenoussodium valprate was as effective as intravenous phenytoin for SE con-trolled and risk of seizure continuation.

Conclusion: Intravenous sodium valproate was more effective or saferthan other drugs in patients with status epilepticus.

p618TREATMENT OF STATUS EPILEPTICUS IN THEELDERLY WITH INTRAVENOUS LEVETIRACETAMS. Eue, M. Grumbt, A. Irimie, A. Latsch, M. Mueller, A. Schulze,and O. SepsiKlinikum Bernburg GmbH, Bernburg, Germany

Purpose: We assessed the efficacy of LEV IV in the treatment of vari-ous types of status epilepticus (SE) in the elderly.

Method: LEV IV was administered at dosages of 1000, 2000 or 3000mg either as an infusion (1000 mg in 100 ml NaCl 0.9%, 15 minutes innonconvulsive SE) or fractionated (500 mg in 20 ml NaCl 0.9%, 1–2 min-utes in convulsive SE). Termination of SE was the effectiveness criterion(defined clinically in convulsive SE, electroencephalographically in non-convulsive SE). Tolerability was assessed by evaluating treatment-related adverse events (AEs).

Result: In the last five years we have treated 59 elderly patients (meanage 76.6 years, range from 65 to 95 years) with LEV IV with varioustypes of SE. In general, LEV was administered as second-line therapy,after benzodiazepines.

Overall, LEV terminated SE in 62.7% of the patients (37/59). LEVwas most effective in terminating simple partial SE (12/15, 80%) but alsoeffective in nonconvulsive SE (7/11, 63.3%) and complex partial SE (18/33, 54.5%). Almost of the patients had a symptomatic epilepsy (94.9%)and there was no case of a (secondary) generalized SE in this study.

Serious AEs were not reported. Prolonged somnolence (especially invery old patients) was reported, but it was difficult to determine whetherthis was caused by LEV, benzodiazepines and/or post-seizure twilightstate.

Conclusion: LEV IV is an alternative in the treatment of partial convul-sive (simple and complex partial) and nonconvulsive SE in the elderly.

Epilepsy Surgery 5Wednesday, 03 October 2012

p619MNESIC PERFORMANCE AFTER SELECTIVE TRANS-CORTICAL AMYGDALOHIPPOCAMPECTOMY INPATIENTS WITH TEMPORAL MESIAL SCLEROSISR. L. Aguilar-Estrada, M. A. Alonso Vanegas, and A. R. MartinezInstituto Nacional de Neurolog�a y Neurocirug�a ManuelVelasco Suarez, Mexico City, Mexico

Purpose: Determine the effectiveness of selective transcortical amygd-alohippocampectomy on seizure control and to assess the cognitive

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performance, especially memory in patients with left mesial temporalsclerosis before and after surgery

Method: We evaluated 28 patients with refractory epilepsy secondaryto left mesial temporal sclerosis who underwent selective transcorticalamygdalohippocampectomy by Inferior Temporal Gyrus (ITG) duringthe period between 2000 and 2010 at the National Institute of Neurol-ogy and Neurosurgery MVS. We performed preoperative study proto-col, including neuropsychological tests to determine the preoperativecondition. Patients were then retested to assess their postoperativecondition.

Result: They were followed an average of 56 months. The mean agewas 35.14 years. 53.6% female, and 46.4% male. The 71.4% of patientshad seizure control after surgery (Engel Ia and Ib), while 28.6% was in Icand Id Engel. Before surgery 68% of patients had mild abnormalities inmemory. As for the semantic fluency disorders 24% had mild, 47.5%with moderate and 28.5% with severe alterations. We found a positiverelationship between age of disease onset and rate of improvement for thetest of direct digits (R equal to 0.410, P = 0.37). There had not a moreimpaired mnesic performance postoperatively.

Conclusion: Selective tanscortical amygdalohippocampectomy by ITGfor patients with left mesial temporal sclerosis, while providing a compa-rable seizure control with international standards, was not related to aadditional deficit verbal memory in patients.

A good control of seizures in patients after surgery is associated withimproved mnemonic performance in all categories, especially in verballearning. The preoperative neuropsychological assessment showed Mem-ory impairment in most of the patients, and worked as an important diag-nosis and prognosis test.

p620EPILEPSY SURGERY: LEAVING THE LESIONBEHIND?S. Chinnasami, A. W. Mcevoy, C. Scott, T. Wehner, J. Duncan,and B. DiehlThe National Hospital for Neurology and Neurosurgery,London, UK

Purpose: To describe two patients with epileptogenic zones distant fromMRI lesions.

Method: We reviewed 246 patients who underwent resections for focalepilepsy over the last 5 years to identify patients with epileptogenic zonesand resections distant from MRI lesions, in non-lesional brain regions.

Result: Two of 246 patients were identified. Patient 1: 36 year old manwith daily seizures (asymmetric tonic arm posturing with falls) sincechildhood. Scalp EEG showed bilateral slowing and midline ictal pat-terns. MRI revealed left hippocampal sclerosis, FDG-PET showed rightfronto-parietal hypometabolism. Intracranial EEG study designed oncareful analysis of semiology and neurophysiological findings showedseizures from the right supplementary motor area. Resection of ictalonset zone led to seizure freedom, with 9 months to date (Histopathol-ogy: non-specific). Patient 2: 30 year old man with daily automotor sei-zures and remote history of visual auras. Scalp EEG showed rare sharpwaves in the left temporal region; ictal EEG lateralized to left hemi-sphere. MRI revealed cortical dysplasia or low grade glioma in theupper bank of the left calcarine fissure with normal temporal lobes.Intracranial EEG evaluation covering lesion and left temporal lobe con-firmed left hippocampal seizure onset. Following left anterior temporallobe resection, he has been seizure free for 2 months (Histopathology:hippocampal gliosis)

Conclusion: The epileptogenic zone may be distant from MRI lesions.Careful analysis of clinical, neuroimaging, and electrophysiological datais crucial, even in the presence of a structural lesion. Longer follow up isneeded to assess ultimate outcome.

p621CLINICAL CHARACTERISTICS AND OUTCOME OFSURGERY FOR CHILDREN AND ADOLESCENTSS. J. Sattaluri, M. Panigrahi, and S. MadigubbaKrishna Institute of Medical Sciences, Secunderabad, AndhraPradesh, India

Purpose: To assess the clinical characteristics and postsurgical out-comes in children and adolescents with TLE.

Method: Retrospective analysis of ictal VEEG, MRI, ictal SPECT,FDG PET, neuropsychology and pathology data was performed in 80children and adolescents with refractory TLE who underwent surgeryand had at least one year post-surgery follow-up. Presurgical evaluationwas done with non-invasive protocol. Ictal SPECT & FDGPET was per-formed in all the patients with a discordance of ictal EEG & MRI data.Outcome was assessed according to Engel's outcome classification(Favourable: Engel's class I & IIA).

Result: There were 24 children (2–12years) and 56 adolescents; Theduration of follow up was 12–78 (mean38.4) months and the age of onsetof epilepsy ranged from 4m to 15 years. At the last follow up 18 (75%)children and 39 (69.6%) adolescents were seizure free. Auras were morecommon in adolescents, while developmental delay, below normal IQand secondary generalized and multiple seizures were more frequent inchildren (p<0.05). Interictal-EEG showed multifocal and generalized dis-charges significantly more frequent in children than adolescents(p<0.001). Hippocampal sclerosis was the commonest pathology, notedin 76.8% of adolescents and 62.5% children. Isolated focal cortical dys-plasia was more frequent in children (21%) than adolescents (12.5%).Dysplasia was more common in children <10 years (38.4%). After step-wise regression analysis, variables found to be significant (p=<0.05) andpredicting an unfavourable outcome were acute post operative seizuresand non-lateralizing ictal-EEG findings.

Conclusion: Children with TLE have distinct clinica, EEG and pathol-ogy features when compared to adults. Favourable outcome can beobtained in children and adolescents after surgery for TLE.

p622EPILEPSY SURGERY IN CHILDREN WITH DIFFI-CULT-TO-TREAT EPILEPSY IN THE SOUTH REGIONOF SWEDEN – LONG-TERM FOLLOW-UPT. C. Hallbççk*, E. Tideman�, J. Lundgren�, and I. Ros�n�

*Paediatric Neurology, Sahlgrenska Academy, Gothenburg,Sweden; and �Lund, Sweden

Purpose: Resective epilepsy surgery in early childhood has become animportant treatment option for selected infants and children with epi-lepsy. We describe experience and clinical outcomes in all children whounderwent resective surgery for epilepsy in the south region of Sweden.The study is a long-term follow-up of all children who underwent epi-lepsy surgery, at the University Hospital in Lund from the beginning in1991b until 2007.

Method: All children under 18 years of age who had resective surgeryfor the purpose of treating epilepsy within the south region of Sweden atthe Lund University Hospital epilepsy surgery program between the startin 1991 and 2007 were assessed for cognitive functioning, mental health,present psychological, occupational and social functioning, QOL andexpectations. Follow–up was between 5 and 21 years. Review of medicaldocuments for demographic data and seizure-related characteristics suchas etiology, post-operative seizure frequency, pre and post-operative cog-nitive function, long-term complications and re-operation rates were ana-lyzed by retrospective examination of the clinical records.

Result: Forty-seven children were included in our cohort with a medianage at surgery of 8 years (range 0.5–18.16 years). Surgical procedures

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comprised 15 lesionectomies, 16 lobar resections, six multilobar resec-tions, six functional hemispherectomies, two callosotomies, one discon-nection, and one subpial transection. 19/47 (40%) children underwentreoperation. Three of these were disconnections of hypothalamus ham-artomas. 23/47 (50%) children achieved seizure freedom. 6/47 (13%)demonstrated more than 75% improvement in seizure frequency, 7/47(15%) 50 - 75% improvement in seizure frequency and no children hadan increase in seizure frequency. Postoperative complications includedsubsequent shunt procedure in 1/7 (14%) children undergoing hemispher-ectomy, one child had a peroperative hemorrhage without any sequel andone an infraction with a subsequent light paresis. Two children were deadat follow-up. One died from SUDEP and one while having an epilepticseizure.

Conclusion: Epilepsy surgery in children offers suitable candidates agood chance of significantly improved seizure outcome even after long-term follow-up.

p623RESECTIVE SURGERY BY INTRACRANIAL MONI-TORING IMMEDIATELY AFTER CORPUS CALLOSOT-OMY IN ADULT NON-LESIONAL FRONTAL LOBEEPILEPSIESY. Cho, B. I. Lee, K. Heo, M. K. Lee, D. Kim, and J. W. ChangSeverance Hospital, Yonsei Univ. College of Medicine, Seoul,Korea

Purpose: Non-lesional frontal lobe epilepsy (FLE) often fails to localizeictal onset because of its rapid propagation through corpus callosum. Suc-cessful identification of focal onset and resective surgery long after cor-pus callosotomy (CC) has been reported in childhood epileptics,especially Lennox-Gastaut syndrome. We performed immediate intracra-nial monitoring after partial CC and resective surgery in adult non-lesion-al FLE patients.

Method: Three adult FLE without lateralizing features received resec-tive surgery between 2008 and 2011. Subdural electrodes were placedimmediately after CC and extra-operative intracranial monitoring wasdone from the next day of CC.

Result: All had frequent seizures (one, 8 per month; two, daily attacks)before surgery. Scalp video-EEG monitoring confirmed frontal lobe-ori-gin, but failed to lateralize seizure onset. Semiologic features were notinformative (one had predominantly tonic posturing; two had hypermotorseizures) for lateralization. Neuroimaging findings were not helpful.Intra-operative electrocorticography after partial anterior CC failed tolateralize onset, and bilateral symmetric subdural electrodes were placedover frontal lobes. Extra-operative monitoring showed lateralized interic-tal discharges in all, and two of them also showed localized ictal onset.One patient didn't experienced seizure. Two patients had clearly lateraliz-ing semiologic features which were never found on scalp monitoring.Seizure outcome was successful: two had Engel 1B (rare simple partialseizures only) and one, who hadn't have seizure, had 2A outcome. Nonehad significant post-operative neurological deficit.

Conclusion: Simultaneous intracranial monitoring following partial CCmay be considered an alternative option that enables resective surgery inpatients with non-lateralized FLE.

p624RESULTS OF EPILEPSY SURGERY WITH NON INVA-SIVE METHODS MOROCCAN EXPERIENCE ABOUT 51CASESA. Mrani, A. Khamlichi, H. Belaidi, F. Lahjouji, and R. OuazzaniHospital of Specialities, Rabat, Morocco

Purpose: Epilepsy is a common and disabling condition. Medical treat-ment fails to control seizure in about 20–30% of patients. The burden ishigher in developing countries because of the number of patients, insuffi-cient infrastructure and problem of access to drugs and explorations. Epi-lepsy surgery was suggested to offer an extremely powerful treatmentoption.

Method: Fifty one patients with intractable complex partial seizure weretreated with temporal lobectomy. We use non-invasive methods, i.e. theclinical seizure pattern; interictal and ictal scalp EEG; magnetic reso-nance imaging (MRI); neuropsychological testing and all converged toindicate a localized abnormality.

Result: Thirty one of 51 (60%) are seizure and aura-free (Engel's class I-A) with a mean follow-up time of 4 years (1–7 years), and twelve (23,5%) no longer take antiepileptic drugs. Our series includes twenty ninecases (57%) of hippocampal sclerosis and twenty two cases (43%) ofmass lesions mostly represented by DNET and cortical dysplasia. Ourstudy takes into account outcome predictive factors especially age ofonset, febrile convulsion history, duration of epilepsy, preoperative sec-ondarily generalized tonic-clonic seizure, age at surgery and preoperativeseizure frequency.

Conclusion: The results of our series are comparable of results obtainedin developed countries, which is encouraging to develop this disciplinedespite the material constraints.

p625COMPLICATIONS OF EPILEPSY SURGERY IN SWE-DEN 1996–2010: RESULTS FROM THE SWEDISHNATIONAL EPILEPSY SURGERY REGISTERJ. Bjellvi*, A. Edelvik*, G. Ekstedt*, R. Flink�, B. Rydenhag*,and K. Malmgren**Sahlgrenska Academy, University of Gothenburg, Gothenburg,Sweden; and �Uppsala Akademiska Hospital, Uppsala, Sweden

Purpose: Patients need detailed risk information as part of pre-surgicalcounseling when considering epilepsy surgery. In this study we haveinvestigated major and minor complications related to epilepsy surgeryin Sweden 1996–2010.

Method: The Swedish National Epilepsy Surgery Register providespopulation-based data on all patients (adults and children) operated inSweden since 1990 (completely prospective from 1995), including exten-sive pre-operative data, surgical data including complications, and post-operative follow-up. We have analysed complications in relation to typeof surgery for the period 1996–2010. Complications are classified asmajor (affecting daily life and lasting >3 months) or minor (resolvingwithin 3 months).

Result: 858 therapeutic epilepsy surgery procedures were performed1996–2010, of which 153 were reoperations. There were no postopera-tive deaths. Major complications occurred in 23 procedures (2.7%),minor complications in 66 (7.7%). In temporal lobe resections (N=518),there were 13 major (2.5%) and 39 minor complications (7.5%), in extra-temporal resections (N=272) 9 major (3.3%) and 23 minor complications(8.5%), and in nonresective procedures (N=61) 1 major (1.6%) and 4minor complications (6.6%).

Conclusion: This is the largest reported prospective series of complica-tion data in epilepsy surgery. The complication rates comply well withpublished results from single centers, confirming that epilepsy surgeryperformed in the six Swedish centers is safe. Compared to previouslypublished results from the same register [Rydenhag et al, Neurosurgery,49:51–57, 2001], the complication rates are lower for any surgical proce-dure as well as for temporal resections, extratemporal resections, andnonresective procedures.

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p626SURGICAL EXCISION OF TEMPORAL GLIONEURO-NAL TUMOURS – RISK FACTORS FOR PSYCHIATRICSEQUELAE?O. Solanke*, R. Chelvarajah�, J. Moriarty�, C. E. Polkey�, andR. Selway�

*Guy's, King's and St. Thomas’ Hospitals Medical School,London, UK; �Queen Elizabeth Hospital Birmingham,Birmingham, UK; and �King's College London, London, UK

Purpose: We present data from our surgical series to investigate theassociation of anxiety and depression with surgical excision of temporalglioneuronal tumours. We suggest risk factors for development of thesepsychiatric symptoms.

Method: We reviewed the case-notes of each patient. Telephone inter-views were carried out with patients/carers to complete the HamiltonAnxiety Rating Scale (HARS) and the Becks Depression Inventory(BDI).

Result: Thirteen patients underwent surgery for resection of temporalglioneuronal tumours. Ages at surgery ranged from 11 to 54. Six patientshad no anxiety (HARS score <17) or depression (BDI score 1–10) aftersurgery. Five achieved seizure freedom from the time of surgery. One sei-zure-free patient who suffered mental health problems prior to surgeryencouragingly saw resolution of these symptoms post-operatively. Fourof the five seizure-free patients had non-dominant side surgery. Sevenpatients experienced psychiatric difficulties post-operatively, one ofwhich was diagnosed with psychiatric disturbance pre-operatively. Allcontinued to have seizures post-operatively. Four had moderate andsevere anxiety (HARS score above 25) of which two had moderatedepression (BDI score 21–30) and one patient had borderline clinicaldepression (BDI score 17–20). These latter five patients had dominantside surgery.

Conclusion: While psychiatric disability is relatively common with sur-gical excision of temporal glioneuronal tumours, achieving seizure free-dom following surgery can be associated with the absence of psychiatricsequelae and in one of our cases resolved pre-existing psychiatric distur-bance. Non-dominant side surgery may be associated with achieving sei-zure freedom. We postulate that this perceived association may be due tothe degree of surgical resection.

p627MEG VERSUS EEG LOCALIZATION FOR PRESURGI-CAL EVALUATION OF THE INTRACTABLE EPILEPSYA. Koptelova*, A. Melikian�, N. Arkhipova�, A. Stepanenko�,A. Golovteev�, A. Kozlova�, O. Grinenko�, and T. Stroganova**Moscow State University of Psychology & Education, Moscow,Russian Federation; �Burdenko Neurosurgical Institute,Moscow, Russian Federation; and �Moscow City Hospital No12, Moscow, Russian Federation

Purpose: Magnetoencephalography (MEG) and magnetic source imag-ing (MSI) are techniques that have been increasingly used for preopera-tive localization of epileptic foci. To help elucidate the value of MEG,we assessed the results of whole-head MEG versus video-EEG in the casemanagement of patients undergoing epilepsy surgery.

Method: We studied 19 patients with suspected focal epilepsy whounderwent interictal and ictal video-EEG and, subsequently, interictaland ictal MEG. Nine patients underwent surgical resection of suspectedepileptogenic zone and seven of them – invasive electrocorticography.The results of MSI were classified to define epileptogenic foci accordingto the clastering of interictal and ictal spikes recorded during a 4-hourrecording session. The data were analyzed to determine to what extentthe results of MSI correlated with video-EEG determined irritative zones.

Result: In 4 of 19 cases MSI determined localization regionally corre-lated to video-EEG data (that is, showed the same lobe). In thirteen casesMSI showed additional epileptogenic foci that ictal video-EEG wasunable to identified. In six cases, MSI was used to guide invasive elec-trodes to locations that otherwise would not have been targeted and pro-vided unique localization data, not evident from other imagingmodalities, that strongly influenced the surgical management of thepatient. In seven patients, for whom data from invasive electrocorticogra-phy were available, the MSI was highly correlated with the zone of sei-zure origin identified by electrocorticography.

Conclusion: Magnetic source imaging can provide critical localizationinformation that is not available when other noninvasive methods, suchas video-EEG and MRI, are used.

p628EPILEPSY SURGERY FOR REFRACTORY EXTRATEM-PORAL EPILEPSIES. UP TO TEN YERS FOLLOW UPA. Siatouni*, S. Gatzonis*, N. Georgakoulias�, S. Korfias*,C. Tsekou*, T. Bouras*, T. Papasilekas*, E. Aggelopoulos*,M. Papathanassiou*, P. Patrikelis*, I. Kaskarellis*,E. Patsouris*, and D. Sakas**Athens Medical School, Athens, Greece; and �Athens GeneralHospital ‘‘G. Genimatas’’, Athens, Greece

Purpose: The surgical approach is an established method for treatmentof refractory partial epilepsy. The presurgical evaluation in patients withextratemporal epilepsies is aiming to define the boundaries of epilepto-genic zone and the function of possibly removable cortical area in orderto plan the operative procedure, and to estimate the post surgical progno-sis.

We present the results of the surgical treatment of 31 patients sufferedfrom extratemporal refractory focal epilepsy who continue to be moni-tored regularly in our department.

Method: 31 patients, aged 11–43, 25 men and 6 women, who were trea-ted surgically for drug-resisting epilepsy of extratemporal origin. 9patients suffered from non-lesional epilepsies. 22 patients suffered fromlesional epilepsies which resulted from malformations of cortical devel-opment, vascular malformations, tumors and gliosis from old injuries orsurgery. The presurgical protocol includes history, EEG, long termVideo-EEG, high resolution structural and functional imaging techniquesand neuropsychologic studies in order to compose a clinical scenario forthe topography of epileptogenic zone. All of them underwent invasivelong term-EEG monitoring as a standard procedure for the precise locali-zation of the pacemaker zone and cortical stimulation in the definition ofeloquent cortical areas

Result: 58% (18/31) of the patients are classified as Engel I after the sur-gical procedure (follow-up 1–10 years). 8 (25, 8%) patients show worth-while seizures reduction (Engel II, III) and 5 patients do not show anyappreciable improvement (Engel IV)

Conclusion: Surgical treatment of extratemporal epilepsies is a favor-able therapeutic procedure which offers more than 50% seizure free ratesand low incidence of serious complications.

Epilepsy Surgery 6Wednesday, 03 October 2012

p629BASAL TEMPORAL LANGUAGE TESTING INPATIENTS UNDERGOING INVASIVE EEG STUDIESC. Scott*, S. Kovac�, T. Wehner�, R. Rodionov�, A. W. Mcevoy§,and B. Diehl�

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*Telemetry Unit, London, UK; �Department of Clinical andExperimental Epilepsy, London, UK; �UCL Institute ofNeurology, London, UK; and §National Hospital for Neurology& Neurosurgery, London, UK

Purpose: The involvement of basal temporal lobe in language and purealexia has been previously described but not widely investigated. Wereviewed electrical cortical stimulation (ECS) in all patients with basaloccipito-temporal intracranial electrode coverage for localisation of theictal onset zone performed over the past 3 years, in whom mapping of thatarea was performed (n=7).

Method: ECS of basal occipito-temporal areas and testing of reading,naming, writing and comprehension was performed using 50Hz stimula-tion, 3–5s duration, mean 4mA. 5/7 patients were left language dominantand 2/7 had bilateral speech representation. 2/7 had lesions (1 mesial tem-poral, 1 basal temporal). Language mapping was scored by two indepen-dent reviewers and errors influenced by after discharges were excluded.

Result: ECS was performed successfully in 6, in one patient extensivemapping was impossible due to after discharges. Basal language areaswere identified in 3 patients. The number of contacts showing some lan-guage deficit was 2–3 per patient (total 8 contacts), all overlying the fusi-form gyrus (5.8–8cm from the tip of temporal pole). Object naming,auditory comprehension, reading and reading comprehension were mostcommonly disrupted by ECS.

Conclusion: That we found basal temporal language area in only 3 of 6patients may reflect sampling error; comprehensive coverage of this areais technically difficult, the eloquent area may be small and dispersed, andin some patients lesions may displace function. When identified, it canprovide useful information to aid counselling regarding postoperativenaming difficulties if resection of this area is required.

p630SURGERY FOR TEMPORAL LOBE EPILEPSY WITHNORMAL MR IMAGING: SEIZURE OUTCOME, YIELDOF RE-EVALUATION AND OUTCOME FOLLOWINGREOPERATIONM. M. Ali, W. J. Hader, N. Pillay, S. Wiebe, P. Federico,L. B. Espinosa, and M. Opoko-DarkoCalgary University, AB T2N2T9, Canada

Purpose: To review the seizure outcome, location of seizure recurrence,and outcome of reoperation for temporal lobe epilepsy with normal MRImaging.

Method: We retrospectively reviewed the records of all patients whounderwent temporal lobe surgery with nMRI between 2000 and 2010 atCalgary Epilepsy Program. We reviewed the location of seizure recur-rence and seizure outcome following reoperation.

Result: We identified 47 patients who underwent TLE surgery withnMRI.32 patients underwent anteromesial temporal lobe resection, 11trans cortical selective amygdalo-hippocampectomy, and 4 neocorticec-tomy. Seventeen patients underwent intracranial electrodes implantationprior to the resection. On average follow-up of 51 months, 29 patients(61%) had either Engel class I or II outcome. Fourteen out of the 18remaining patients (78%) patients had re-evaluation including repeatvideo-EEG monitoring and high resolution MRI and intracranial moni-toring (n=5). The focus of recurrence was: contralateral temporal 4(28%), ipsilateral posterior neocortical 7 (35%), Insular 1 (7%), Frontal 1(7%), and residual hippocampus in 1 (7%). Out of the 7 patients who hadre-operation, only 1 patient (14%) was seizure free on last follow-up.

Conclusion: Temporal lobe resection in well-selected patients withnMRI can provide favorable rates of seizure freedom. The location ofrecurrence in patients re-evaluated after failure was felt to be in the con-tralateral temporal lobe or ipsilateral posterior temporal lobe rather than

in an extratemporal location, however reoperation failed to improve theoutcome in the majority.

p631LONG-TERM OUTCOME OF SURGERY IN PATIENTSWITH EXTRATEMPORAL EPILEPSYP. Hanakova*, R. Kuba�, M. Brazdil�, J. Hemza�, Z. Novak�,J. Chrastina�, M. Hermanova§, H. Oslejskova*, and I. Rektor�

*Epilepsy Center Brno, Brno University Hospital and Faculty ofMedicine, Masaryk University, Brno, Czech Republic; �CentralEuropean Institute of Technology (CEITEC), MasarykUniversity, Brno, Czech Republic; �Epilepsy Center Brno; St.Anne's University Hospital and Faculty of Medicine, MasarykUniversity, Brno, Czech Republic; and §St. Anne's UniversityHospital and Faculty of Medicine, Masaryk University, Brno,Czech Republic

Purpose: To evaluate long-term efficacy of surgery in patients withrefractory lesional and non-lesional extratemporal epilepsy.

Method: We retrospectively analysed 73 patients (46 men and 27women) with extratemporal epilepsy, who underwent resective surgeryin St. Anne's University Hospital in Brno, the Czech Republic, betweenAugust 1995 and January 2010. The average age at surgery was28.3€11.4 years (range 1- 51 years). Magnetic resonance imaging did notdemonstrate a lesion in 32.9% of patients. Surgical outcome was annuallyassessed by using Engel's modified classification one until five yearsafter surgery and at the latest follow-up visit.

Result: Following the surgery, Engel Class I outcome was found in52.1% after 1 year, in 55.0% after 5 years and in 50.7% of patients at thelast follow-up (the average 6.15€3.84 years) in the whole group. A statis-tically significant association was found between tumour etiology andgood outcome (v 2(2) = 6.67; p=0.035). There was confirmed a statisti-cally significant association between a lesion on the preoperative mag-netic resonance imaging and the reduction in seizure frequency (v2 (1)=6.62; p=0.01). No statistically significant difference between durationof epilepsy and surgical efficacy was found.

Conclusion: Our results are comparable to recent publications. 50–55%of patients with extratemporal epilepsy are seizure-free after surgery.

p632PRACTICAL VALUE OF INTRAOPERATIVE ELEC-TROCORTICOGRAPHY IN CHILDRENP. Krsek, R. Lesko, A. Jahodova, M. Kudr, J. Zamecnik,V. Komarek, and M. TichyMotol University Hospital, Prague, Czech Republic

Purpose: To study a practical value of intraoperative electrocorticogra-phy (ECoG) in pediatric excisional epilepsy surgery.

Method: ECoG recordings performed in 90 children operated onbecause of intractable focal epilepsy in Motol Epilepsy Centre between2002 and 2011 were retrospectively analyzed. Completeness of resectionof cortical regions exhibiting significant ECoG abnormities was assessed.Findings were related to surgical, histological and seizure outcome dataof patients.

Result: 37 patients had ECoG only before the resection, 34 subjectsunderwent ECoG both before and after resections, 19 patients had ECoGafter a long-term invasive monitoring. Based on ECoG findings, surgicalplans were modified in 27 subjects (Group 1); in 54 patients were notchanged (Group 2). In nine patients, there was a reason for a modificationthat was not done because of surgical causes (Group 3). All the groups

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were etiologically diverse. In Group 1, modifications of surgical planswere equally based on ECoG findings before and after resections. Histol-ogy of the brain tissue in extended resections was always abnormal.There were no significant differences in proportion of resections assessedas ‘‘complete’’ as well as seizure outcomes between Groups 1 and 2. Nosubjects in Group 3 were rendered seizure-free.

Conclusion: ECoG findings modified surgical plans in a significant sub-group of pediatric epilepsy surgery patients, regardless the etiology. Bothpre-resective and post-resective ECoG was useful in our series. Long-term seizure outcomes in patients undergoing extended resectionsaccording to ECoG were comparable to subjects with no need of surgicalplan modifications. Supported by grants CZ.2.16/3.1.00/24022 and IGANT/11460-4.

p633MULTIMODAL 3D VISUALISATION FOR PLACEMENTOF INTRACRANIAL EEG ELECTRODESR. Rodionov*, C. Vollmar�, A. Miserocchi�, C. Micallef�,B. Diehl�, A. W. Mcevoy�, and J. Duncan**UCL Institute of Neurology, London, UK; �University ofMunich, Munich, Germany; and �National Hospital forNeurology and Neurosurgery, London, UK

Purpose: Accurate placement of intracranial EEG electrodes is crucialfor optimal results and to mimimize risk. Multimodal neuroimaging pro-vides very useful data for ensuring more accurate and safer placement ofelectrodes. We developed and implemented a multimodal, interactive 3Dvisualisation pipeline for presurgical planning and import of this informa-tion into the neuronavigation system for use at the time of surgery.

Method: Images of different modalities (MRI, SPECT, PET, fMRI,DTI, EEG-fMRI, MEG) are coregistered into the base T1-weighted MRimage and converted into colour-coded volume- or surface-rendered 3Dmodels. A 3D model of surface veins serves as a landmark for navigationand indicates areas requiring special care during surgery. The compositedataset is used to plan electrode placement. All images are coregisteredto the navigational T1 image acquired shortly prior to the surgery andconverted into binary labels and fused onto the navigational image. Theresulting image is used to create 3D models which is uploaded on the neu-ronavigation system.

Result: The method was applied in 20 patients with refractory focal epi-lepsy. The multimodal display helped electrode placement and accuracyof placement of 3D models was confirmed intraoperatively.

Conclusion: 3D models of multimodality neuroimaging data aid accu-rate and safe placement of intracranial electrodes.

p634CHRONOTOPOLOGY OF NEUROPHYSIOLOGICMARKERS FOR EARLY AND LATE EPILEPTOGENE-SIS AND SURGERY OF DRUG-RESISTANT TEMPORALLOBE EPILEPSYS. Kravtsova, T. Stepanova, V. Kasumov, V. Bersnev,R. Kasumov, and K. SebelevRussian A.L. Polenov Neurosurgical Institute, St. Petersburg,Russian Federation

Purpose: Over 30% of epileptic patients suffer uncontrolled by medica-tion seizures. This study aimed to examine neurophysiologic mechanismsof epileptogenesis and to optimize surgical treatment of drug-resistanttemporal lobe epilepsy.

Method: A program including neurophysiologic (EEG, ECoG, SEEGvia subdural and deep electrodes) and visualizing (functional MRI)

technologies to study chronotopology of epileptogenesis has been elabo-rated. Electroclinical diagnostic examination and surgical treatmentresults in over 200 drug-resistant temporal epilepsy patients aged 19–50were analyzed.

Result: Based on critical chronotopology of electrographic trait-markersparticularities of preclinical, early (temporal) and late (extratemporal)epileptogenesis were depicted reflecting clinical-neurophysiologic formsof focal and multifocal temporal epilepsy. Monotemporal epileptogenesisis characterized by peculiar localization of the epileptic focus: in our ser-ies ECoG-SEEG studies revealed a combined neocortical and limbic(hyppocampus, amygdala) damage in 79% of patients. This optimizestechnology of open surgical treatment (anterior temporal lobectomy)with additional use of multiple subpial transection in eloquent cortex.Morphofunctional basis of extratemporal links of epileptogenesis isamounted by integral brain systems ensuring cerebral homeostasis:according to EEG-SEEG data limbical-brainstem pathways of epileptiz-aton were followed-up – hippocampus and amygdala via thalamic ante-rior nuclei are involved in cyclic Papez and Livingston-Escobar-Yakovlev systems, forming multifocal forms (bitemporal, fronto-tempo-ral epilepsy etc.), which is of importance in neuromodulating interven-tions.

Conclusion: The presented date demonstrated that neurophysiologicmarkers appear a reliable method to evaluate regularities of epileptogene-sis at the cortical, limbic and brainstem structure levels. The dynamics ofepileptogenesis optimizes strategy of differentiated surgical treatment ofdrug-resistant temporal lobe epilepsy.

p635CURRENT STATUS AND PHARMACOECONOMICS OFEPILEPSY SURGERY IN DEVELOPING COUNTRIESLIKE INDIAM. M. MehndirattaG.B.Pant Hospital, New Delhi, India

Purpose: To describe the Current Status and Pharmacoeconomics ofepilepsy surgery in developing countries like India.

Method: A survey was conducted through email to different institutesengaged in epilepsy surgery to calculate the Cost of investigations, medi-cal and surgical treatment for epilepsy.

Result: As per the recent census of Government of India, the populationof India is more than one billion. There are only 1000 neurologists toserve this population. At any given time there are around 10 million epi-leptics in India. Approximately two million epileptics require surgery fortheir uncontrolled epilepsy. If a person with epilepsy undergoes forworkup for epilepsy surgery, the expenses involved on investigations likereassessment by conventional EEG, epilepsy protocol MRI brain,SPECT, Video-EEG, Neuro-psychological analysis etc will be approxi-mately US$ 1000. The cost of epilepsy surgery or implantation of VagusNerve stimulator is likely to be around US$ 6000. If we sum up expensesin all categories at a minimum cost level, it is likely to be 7800 USD.India is classified in the category of Low income group by WHO ranked160th in the world and per capita income by the Atlas method for India isUSD 530.

Conclusion: In the absence of comprehensive medical insurancescheme and because of low PCI, to afford epilepsy surgery by an averageIndian is literally is out of reach for a common man.

p636MITOCHONDRIAL DISORDERS IN THE NEOCORTEXOF PATIENTS WITH REFRACTORY EPILEPSYM. A. Alonso Vanegas*, V. Campos*, J. Villeda*,F. Fernandez*, and K. Carvajal�

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*Instituto Nacional de Neurolog�a y Neurocirug�a, DistritoFederal, Mexico; and �Instituto nacional de pediatria, DistritoFederal, Mexico

Purpose: In this study we evaluated activity of NADPH-d, CKmit,VDAC, NOS and NeuN in neocortical tissue of patients with refractorytemporal epilepsy

Method: We studied 10 cases with temporal epilepsy (8 males and 2females). 4 with epilepsy secondary to tumors and 6 cases with mesialtemporal lobe epilepsy. All patients were studied according to standard-ized presurgical protocol and submitted to temporal lobectomy and amig-alohippocampectomy. We studied activity and distribution of NADPH-d,CKmit, VDAC, NOS and NeuN, in biopsies of the temporal cortex. Thesamples were studied by the NADPH-d- technique and immunohisto-chemistry.

Result: NADPH reactive neurons were localized preferentially in layersIII and VI and in the subjacent white matter of the temporal cortex, theneurons in layer VI were larger and significantly reactive to NADH-d.VDAC and NeuN expression was enhanced in layer VI, whereas CKmitand NOS showed a decrease in all cases, Epileptic neurons also showedhypertrophy, cytomegaly, dysmorphic and hyperchomatic, morphology.Ballon cells were observed in 3 patients. We also observed expression ofNADPH subunits in reactive astrocytes and all components of the neuro-phil.

Conclusion: These results suggest a causal relationship between theactivities of respiratory enzymes and metabolic processes that contributeto damage, oxidative and /or mitochondrial dysfunction that can be bothan important cause and/or a consequence of prolonged seizures and couldrepresent changes in brain plasticity in these patients. This study was sup-ported by the CONACYT of Mexico (grants J010.0170/2010) and theAcademy of Sciences of Hungary (grantsETT577/2006, RET67/2005).

p637SEIZURE OUTCOME AND ETIOLOGIES IN FRONTALLOBE EPILEPSY SURGERY IN SWEDEN 1990–2009B. Rydenhag*, R. Flink�, and K. Malmgren�

*Sahlgrenska Academy, University of Gothenburg, Gothenburg,Sweden; �Uppsala Akademiska Hospital, Uppsala, Sweden; and�Sahlgrenska Academy at Gothenburg University, Gçteborg,Sweden

Purpose: To present two-year outcome data from a Swedish nationalprospective population based series of adults and children operated forfrontal lobe epilepsy 1990–2009.

Method: Data from the Swedish National Epilepsy Surgery registerwere analysed for 1990–2009. The register includes data from all surgicalprocedures in Sweden. All patients who had frontal lobe procedures,except reoperations, and who had a two-year follow up were included.The aetiology was also analysed in relation to outcome.

Result: Demographic data for the 128 identified patients are: seizureonset at 8.0 years (3.0–14.0) (median age (interquartile range(Q25;Q75)); surgery at 22.0 years (13.0–35.0); duration of epilepsy: 9.0years (3.9–19.5). 57/128 patients (45%) were seizure free, of these 48(38%) had sustained seizure freedom (ILAE class 1 and 2) at the two-yearfollow up. 9/11 patients (82%) with ganglioglioma (GGL) or dysembryo-plastic (DNET) tumours were seizure free (8 (73%) sustained seizurefreedom). 16/19 patients (84%) with cavernous haemangiomas (CAH)were seizure free (all sustained seizure freedom). 11/37 patients (30%)with malformations of cortical development became seizure free (10(27.0%)) with sustained seizure freedom). 7/32 patients (22%) who hadonly gliosis became seizure free (6 (18.8%) sustained seizure freedom).

Conclusion: Two years after surgery 45% of the 128 patients who hadfrontal lobe resections in Sweden 1990–2009 were seizure free, and 84%

of these had sustained seizure freedom since surgery (ILAE class 1 and2). There is a strong correlation between aetiology and seizure outcomein this prospective, population based series.

p638FUNCTIONAL HEMISPHERECTOMY FOR CONTINU-OUS SPIKE WAVE IN SLOW WAVE SLEEP (CSWS) INPATIENTS WITH EARLY VASCULAR INSULT: FUR-THER EVIDENCE OF THE ROLE OF THE THALAMUSIN PATHOGENESISH. Cross*, A. Mctague*, A. Mclellan�, V. Ramesh�, andW. F. Harkness§

*UCL-Institute of Child Health, London, UK; �Royal Hospitalfor Sick Children, Edinburgh, UK; �Department of PaediatricNeurology, Newcastle, UK; and §Great Ormond Street Hospitalfor Children, London, UK

Purpose: Continuous spike wave in slow wave sleep (CSWS) is an epi-leptic encephalopathy commonly associated with structural brain lesions.We present two cases where a dramatic developmental response was seenwith the abolition of CSWS following hemispherectomy.

Method: Review of clinical, MRI and EEG data.

Result: Case 1 presented age 7 with multiple seizure types in associationwith a congenital left hemiplegia secondary to a right MCA infarct. Herepilepsy rapidly escalated to 200–300 seizures per day, with obtundationand developmental stagnation associated with CSWS resistant to multi-ple treatments including corticosteroids and benzodiazepines. Rightfunctional hemispherectomy at age 10 resulted in a dramatic return ofabilities, particularly speech. At 15 she is now seizure free, attends schooland continues to make developmental gains.

Case 2 presented with seizures and a right hemiplegia in the first yearof life due to a perinatal left MCA infarct. Initial right focal motor sei-zures gave way to periods of behavioural change and developmentalregression associated with CSWS. Overt seizures resolved, but theCSWS remained resistant to medical treatment. A left functional hemi-spherectomy performed at 11 years of age, led to resolution of behaviour-al problems and marked improvement in learning abilities.

Conclusion: Hemispherectomy is an effective treatment for CSWS inthe context of hemi-pathology. These two cases add to the literature andwe suggest that earlier consideration be given to functional hemispherot-omy, even in the absence of overt seizures.

Medical Therapy and Pharmacology 8Wednesday, 03 October 2012

p639LACOSAMIDE AS ADD-ON TO MONOTHERAPY INPATIENTS WITH PARTIAL-ONSET SEIZURES:INTERIM RESULTS OF THE POST-MARKETING VITO-BA STUDY (VIMPAT ADDED TO ONE BASELINE AED)M. Noack-Rink*, T. Mayer�, S. Arnold�, T. Kumke*, andU. Runge§

*UCB Pharma GmbH, Monheim, Germany; �SchsischesEpilepsiezentrum, Radeberg, Germany; �NeurozentrumNymphenburg, M�nchen, Germany; and §NeurologischeUniversittsklinik, Greifswald, Germany

Purpose: To evaluate the efficacy and safety of lacosamide when addedto a single antiepileptic drug (AED) in adult patients with focal epilepsy.

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Method: Six-month prospective, non-interventional study with aplanned enrollment of 500 patients.

Result: Efficacy data are available for 99 patients and safety data for109. Patients were less refractory than those in the pivotal Phase II/III tri-als. Over the final three months of the evaluation period, 77.8% and64.6% of patients experienced a ‡50% and ‡75% reduction in seizure fre-quency and 43.4% were seizure-free (median dose 200mg). Patients witha history of one lifetime AED experienced greater benefit with lacosa-mide than the overall population: 86.7% and 80.0% showed a ‡50% and‡75% reduction in seizure frequency, respectively; 66.7% were seizure-free. When analyzed by concomitant AED, a trend towards greaterimprovement was observed in patients taking non-sodium channel block-ers compared with those taking SCBs: ‡50% and ‡75% responder rateswere 83.0% and 72.3%, respectively, versus 73.1% and 57.7%; seizure-free status was 46.8% versus 40.4%. Physicians judged symptoms in23.2% and 40.4% of patients as ‘‘very much improved’’ or ‘‘muchimproved.’’ TEAE incidence (50.5%) was lower than in the pooled piv-otal trials (81.0% for all doses). The most common TEAEs (‡5%) werefatigue, dizziness and convulsion.

Conclusion: Patients with less refractory disease treated with lacosa-mide as add-on to monotherapy derived therapeutic benefits that exceedthose observed in the pivotal trials. Patients on concomitant nonSCBsalso tended to show better responses to lacosamide than those on SCBs.Sponsored by UCB Pharma

p640CHRONIC VALPROATE ENCEPHALOPATHY WITHREVERSIBLE COGNITIVE IMPAIRMENT AND BRAINATROPHYA. G. Caicoya, R. Yubero, M. Jim�nez De La PeÇa, S. Gil-Robles, and R. ArroyoHospital Universitario Quir�n Madrid, Madrid, Spain

Purpose: Chronic valproate encephalopathy causes a gradual cognitivedecline that may easily be overlooked. Reversible brain atrophy causedby valproate has been reported in children and young adults, but just inone case in an older patient (Thirugnanasampanthan et al., Gen Hosp Psy-chiatry 2006;28:458–462).

Method: We report two cases of adults under prolonged valproate treat-ment showing cognitive slowing and diffuse brain atrophy, being bothconditions reversible after withdrawal of valproate.

Result: A 52 year-old male with treatment-resistant epilepsy on valpro-ate (for about 30 years), clobazam and zonisamide was admitted for epi-lepsy surgery evaluation. Video-EEG monitoring showed complexpartial seizures of right temporal origin and slight slowing of backgroundactivity. Neuropsychological assessment revealed a generalized cogni-tive decline with slowing of speech and information processing. The cra-nial MRI showed diffuse brain atrophy. Chronic valproateencephalopathy was suspected, and valproate progressively withdrawn.The work-up one year later showed an important recovery of the brainatrophy and improvement of cognitive functions in the neuropsychologi-cal assessment.

The other case of chronic valproate encephalopathy was observed in a55 years-old female with partial epilepsy, on valproate for about sevenyears. She complained about dizziness and cognitive slowing. The EEGshowed a left temporal delta focus and frontal bilateral synchronousspike-wave complexes. After complete withdrawal of valproate sheshowed an important improvement of her cognitive processing speed andbrain atrophy.

Conclusion: Patients with cognitive decline and chronic treatment withvalproic acid should always receive a neuroimaging and neuropsycho-logical work-up, in order to identify remediable iatrogenic adverseeffects.

p641ESLICARBAZEPINE USE IN MENTALLY RETARDEDAND REFRACTORY EPILEPTIC PATIENTSA. Fraile, P. E. Bermejo, J. Chamorro, and E. BlancoFundaci�n San Jose, Madrid, Spain

Purpose: Despite the introduction of multiple new antiepileptic drugs(AEDs) in the past 20 years, about 30% of patients with epilepsy con-tinue to experience uncontrolled seizures or significant side effects.This resistance to treatment is even higher in people with mentalretardation. The aim of this study is to present our experience with es-licarbazepine therapy in mentally retarded and refractory epilepticpatients.

Method: This is a retrospective study and we reviewed the medicalcharts of all mentally retarded patients receiving oral eslicarbazepineuntil February 2012. Efficacy was determined according the seizure fre-quency during the month prior to treatment initiation and the month afterthe maximal dosage of eslicarbazepine was attained.

Result: Twenty eight patients (13 men and 15 women) aged 17–61(mean 26.1€12.1) years were enrolled. Twelve suffered perinatal anoxia,seven had epilepsy attributed to a structural cause, six had epilepsy ofunknown cause, and three had Lennox-Gastaut syndrome. The meannumber of AEDs they were taking was 2.3€0.8 and the previous AEDsthey had tried were 7.9€2.2. The mean follow-up was 4.1€2.2 months.Seven (25%) patients had at least a 50% seizure reduction, while a smalldecrease was obtained in another nine (32%). It was discontinued in six(21%) patients because of inefficacy. Side effects were reported in eight(28%) patients.

Conclusion: Eslicarbazepine seems to be effective and safe in mentallyretarded and refractory epileptic patients according to our cohort. Furtherprospective studies on eslicarbazepine efficacy and safety in a large num-ber of this type of patients are warranted.

p642VAGUS NERVE STIMULATION FOR DRUG RESIS-TANT EPILEPSY IN CHILDREN: GAZI UNIVERSITYEXPERIENCEA. Serdaroglu*, E. Arhan�, G. Kurt*, E. Bilir*, K. Baykaner*,A. Erdem*, and E. Durdag**Gazi University School of Medicine, Turkey; and �The Ministryof Health, Ankara Children's Health and Diseases Hematology-Oncology, Education and Research Hospital, Turkey

Purpose: Vagus nerve stimulation (VNS) is an alternative treatment forpatients with drug-resistant epilepsy who are not candidates for resectivesurgery. VNS has been demonstrated to be efficacious, safe. The aim ofthis study was to evaluate the experience of VNS at the Gazi University,and to examine demographic data, types of seizures, and seizure-controloutcomes among treated subjects. This is the first account of VNS in apediatric population in Turkey.

Method: Sixty-three children under eighteen years of age with drug-resistant epilepsy were implanted with a vagus nerve stimulator deviceMay 2000 and November 2011.

Result: The patients’ mean age at vagus nerve stimulator implantationwas 10.92€3.41 years. The most common type of seizure was secondarygeneralized tonic-clonic. All the patients seizure were drug-resistant andall had been treated with an average of 4€2 drugs. Follow-up was com-plete for 92.07% of patients and the mean duration of VNS therapy inthese patients was 49.25€32.20 months. Seizure frequency significantlyimproved with VNS therapy (mean reduction 53.17%) without a signifi-cant reduction in antiepileptic medication burden. Reduction in seizurefrequency of at least 50% occurred in 39.7% of patients and 17.5% ofpatients experienced at least a 75% reduction. Three patients were sei-

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zure-free. Ten patients experienced stimulation-induced symptoms, butdid not require device remova. One patient experienced a wound infec-tion twice and VNS device had to be removed. Three patients diedbecause of reasons not related to VNS implantation, one pneumonia, onesepsis and one sudden death in epilepsy (SUDEP).

p643EXPERIENCE WITH LACOSAMIDE IN A SERIES OFADULTS WITH DRUG-RESISTANT FOCAL EPILEPSYA. Verentzioti*, A. Siatouni�, and S. Gatzonis�

*Evaggelismos Hospital, Athens, Greece; and �Athens MedicalSchool, Athens, Greece

Purpose: To evaluate the efficacy and safety of lacosamide (LCM) asadjunctive therapy in patients with refractory focal epilepsy.

Method: A retrospective study of patients suffering from severe phar-macoresistant partial epilepsy with or without secondary generalizationfrom 2008 until 1/12/2011.

Result: 92 patients (52 men and 40 women) were included in thisstudy. The mean age is 33 years (12–84) and the mean age of seizurestart is 13 years (1–83). Prior to the LCM administration, patients hadreceived ‡ 3 antiepileptic drugs. The mean dosage of LCM was 300mg/ day (range 100–600 mg/d). The mean seizure rate was 13monthly before and 9 monthly after LCM administration (WilcoxonSigned Ranks Test: -4,014, Sign Test: -4,396). 16 patients (17, 3%)are seizure free. Reduction of frequency was reported by 29 (31, 5%)patients (<25%:3, 25–50%: 6, 50–75%: 10, >75%: 10). 18 patients(25, 3%) had no significant improvement. Twenty-eight patients (30,4%) reported drug-related adverse events (AEs); the most commonwas dizziness, double vision and ataxia (21, 4–39, 3%). There wereno serious AEs.

Conclusion: Adjunctive lacosamide significantly reduced seizure fre-quency in patients with severe uncontrolled partial seizures withoutsevere adverse events.

p644EFFECTIVENESS OF LAMOTRIGINE AND LEVETI-RACETAM IN CLINICAL PRATICE: RETROSPECTIVECHART REVIEWC. Deckers*, A. Beun�, G. De Haan�, H. Van Hemert-Van DerPoel*, and J. Van Der Palen�

*SEIN, Zwolle, The Netherlands; �SEIN, Heemstede, TheNetherlands; and �Medisch Spectrum Twente, Enschede, TheNetherlands

Purpose: Evaluation of the effectiveness of lamotrigine and levetirace-tam in a hospital-based cohort of epilepsy patients with localization-related epilepsy.

Method: Medical charts of patients treated at SEIN epilepsy centre werereviewed. Effectiveness of lamotrigine and/or levetiracetam therapy inpatients who were prescribed these drugs because of insufficient seizurecontrol was assessed during the first year of use, with patients serving astheir own controls. Effectiveness was determined by reduction in seizurefrequency.

Result: Effectiveness could be assessed in 174 patients using lamotri-gine and 154 patients using levetiracetam; assessment in remainingpatients was not possible due to various reasons, such as insufficient dataon seizure frequency. Lamotrigine was effective (i.e. >50% reduction inseizure frequency) in 48% of patients and 16% of patients using lamotri-

gine became seizure free. In a multivariate model the following variableswere significant predictors of response to lamotrigine: use of sodiumchannel blocker, use of valproate, number of antiepileptic drugs used,and age. Levetiracetam was effective in 54% of patients and 23% ofpatients using levetiracetam became seizure free. In a multivariate modelthe following variables were significant predictors of response to leveti-racetam: epilepsy duration, use of carbamazepine, and history of psychi-atric disease.

Conclusion: Lamotrigine and levetiracetam are effective drugs in clini-cal practice. Several clinical variables were identified as predictors ofresponse to lamotrigine and/or to levetiracetam.

p645COSTS, WORK ABSENCE, AND ADHERENCE INPATIENTS WITH PARTIAL ONSET SEIZURES TAKINGGABAPENTIN OR PREGABALIND. Labiner*, N. L. Kleinman�, A. Sadosky�, J. Seid�, andR. Martin§

*University of Arizona, Tucson, AZ, USA; �HCMS Group,Cheyenne, WY, USA; �Pfizer, Inc., New York, NY, USA; and§University of Alabama at Birmingham, Birmingham, AL, USA

Purpose: Few studies have examined the burden of epileptic partialonset seizures (POS) from the employer perspective or compared users ofgabapentin and pregabalin in the treatment of POS. This study comparespharmacotherapy and resource utilization of patients with POS newlytreated with gabapentin or pregabalin.

Method: Retrospective data from employees and dependent spouseswith POS starting treatment (index date) with either gabapentin or pre-gabalin were analyzed. At least 6 months of health plan enrollmentpre- and post-index were required. Regression modeling comparedmedical and prescription costs, sick leave, short-term disability, andworkers’ compensation costs, and absence days during the 6-monthpost-index period. Persistence, adherence (percent of days covered),and the impact of copay and copay as a percent of salary on adherencewere modeled.

Result: All costs were statistically similar between the gabapentin andpregabalin cohorts except drug costs (44% higher in the pregabalincohort, P=0.01). Sick leave days, however, were lower in the pregabalincohort than in the gabapentin cohort (P=0.04). Adherence was greater inthe pregabalin cohort (P=0.05) as was persistence, although the latter wasnot significant. Adherence decreased as copay or copay as a percent ofsalary increased beyond specific levels in both cohorts.

Conclusion: Cost, work absence, and medication persistence and adher-ence outcomes associated with gabapentin and pregabalin were found tobe similar in most cases. Even when not significantly different, most out-comes favored pregabalin. The impact of POS on patients and onemployer sponsors is substantial across a variety of metrics.

p646INCREASED LEVETIRACETAM CLEARANCE INPREGNANCY: IS SEIZURE FREQUENCY AFFECTED?E. Mawhinney*, A. I. Hoeritzauer�, B. Irwin*, S. Hunt*,J. Morrow*, and J. Craig**Royal Victoria Hospital, Belfast, UK; and �NHS, UK

Purpose: Background: Emerging data on the teratogenic potential ofvalproate and topiramate have resulted in a prescribing shift towardslamotrigine and levetiracetam in women of childbearing age with epi-lepsy. However use of these AEDs during pregnancy is associated withnew difficulties. It is widely documented that lamotrigine clearance

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increases by up to 330% in pregnancy, with associated increase in seizurefrequency in 39- 45% of women. Early studies show that levetiracetamserum levels also fall by 40- 62% during pregnancy, but in contrast tolamotrigine very little is known about the clinical effect of this observa-tion.

Method: Retrospective chart review was performed for women inNorthern Ireland taking levetiracetam monotherapy during pregnancyfrom 2003 to 2011.

Result: Forty four women taking levetiracetam during pregnancy wereidentified. Deterioration or relapse of seizures was observed in 30.8% ofwomen, improvement in seizure control in 17.9% and no change in51.3%.

Conclusion: Seizure control deteriorated in over 30% of women in thisstudy, towards the upper end of the expected range of 14- 32%. This isthe largest study to date of seizure control in women taking levetiracetamduring pregnancy. These preliminary findings, together with the paucityof evidence in this area, highlight that further research is clearly neededto guide clinicians on the potential clinical impact of this phenomenon.

p647RETENTION OF LACOSAMIDE IN AN THIRD-LINEREFERRAL EPILEPSY CENTREE. V. Van Beijeren, I. Vandesteenkiste, T. Punte, and G. De HaanStichting Epilepsie Instellingen Nederland (SEIN), Heemstede,The Netherlands

Purpose: In order to determine the potential value of lacosamide for theeveryday treatment of epilepsy we examined the retention of the drug inthe outpatient population of our third-line referral epilepsy centre. Somereports indicate that treatment emerging adverse effects may be more fre-quent in patients using sodium-blocking comedication.

Method: A retrospective, observational study of the first 240 outpatientsthat have been treated with lacosamide since March 2009. Informationwas retrieved from the medical records about type and frequency of sei-zures, epilepsy syndrome, comedication and medication history, startdate of lacosamide, target dose, effects and adverse effects, and date andreason for withdrawal of lacosamide.

Result: Data of 212 patients were analysed. After one year follow upretention rate was 66%. Retention did not differ between patients with orwithout sodium-blocking comedication. Reasons for discontinuationwere: no effect (42%), adverse effects (25%) or a combination of both(42%). A positive effect of Lacosamide was reported in 58% of thisrefractory population. One patient became seizure free. Patients reachinghigher maximum dosages were less likely to discontinue LCM.

Conclusion: In a population of patients with medically refractory epi-lepsy retention rate for LCM is higher or comparable with other recentlyintroduced antiepileptic medication, and is not dependent on type of co-medication.

p648THE EXPERIENCE OF THERAPEUTIC NEW ANTIE-PILPTIC DRUG MONITORING (PREGABALINE) INTHE TERTIARY EPILEPSY CENTERJ. Byun, B. S. Kang, J. Lim, B. S. Park, J. W. Shin, Y. S. Kim,K. Chu, and S. K. LeeSeoul National University Hospital, Seoul, Korea

Purpose: We tried to evaluate the kinetics of pregabaline and correla-tion between serum level and seizure control in epilepsy patients in thetertiary epilepsy center.

Method: Adult patients who had been treated with pregabaline as a sub-group of Seoul Epilepsy Registry Cohort were recruited. We obtained theinformation about timing of medication and checked the serum druglevel. Electronic medical records were retrospectively reviewed. Efficacywas measured using a five point scale.

Result: Of total 1338 patients in Seoul Epilepsy Registry, 119 patientswere prescribed pregabaline. The 72 patients were male and mean agewas 42.44 year-old. Mean dose of pregabaline was 296.75mg per day.For 116 patients with polytherapy, mean 2.45 kinds of other antiepilep-tic drugs were also received. Median sample time was 6.5 hours aftermedication. Mean serum level of drug was 2807mg/dL. The serum levelof pregabalin showed linear kinetics with daily dose and inversed corre-lation with median sample time. Although the 75% seizure reductionrate was 89.1%, there was no correlation between drug level and seizurecontrol.

Conclusion: We successfully checked the therapeutic pregabalin levels.The further study about other factors that could affects drug levels, suchas drug-drug interaction and genetic variation, is needed.

p649HYPOTHERMIA IN TWO PATIENTS WITH REFRAC-TORY EPILEPSYJ. Raymackers*, P. Jacquerye*, A. Melin�, F. Dupuis*,F. Li�nard�, F. Evrard*, G. Picard*, K. Van Rijckevorsel�, andM. J. Dupuis**Clinique Saint-Pierre, Ottignies, Belgium; �CHC – CliniqueSt-Joseph, Li�ge, Belgium; and �Centre Neurologique WilliamLennox, Reference Center for Refractory Epilepsy, Universit�Catholique de Louvain, Louvain-la-Neuve, Belgium

Purpose: To draw attention of clinicians to the possible relationshipbetween hypothermia and use of antiepileptic drugs.

Method: We report two cases of patients admitted to a general hospitalbecause of severe apathia associated with probable drug-induced hypo-thermia.

Result: A 43-year-old male patient presented with gait alteration. Hewas suffering from congenital encephalopathy, mental retardation,psychiatric disorder and refractory epilepsy. At the emergency room,he showed altered conscience, without neurological or infectioussigns. Axillar and rectal temperatures were noted 31�C and 30�C,respectively. Axillar temperature further decreased to 29�C. Thepatient was receiving several medications, including antiepilepticdrugs VPA, OXC and TPM, the latter being only recently added.After cessation of TPM, temperature progressively returned to normalvalues.

A 46-year-old female patient developed apathy, anorexia, hypoten-sion, slight blood oxygen desaturation and 36�C hypothermia. She wasreceiving LEV, GBP, VPA and LTG for refractory seizures secondaryto severe perinatal anoxic encephalopathy. One week prior to admission,daily dose of LTG was erroneously doubled. This coincided with thealteration of mental and motor functions. The day of admission, axillartemperature was 33.5�C. Ancillary tests were of little contributionexcept for a chest X-Ray which disclosed right lobar density. Intrave-nous antibiotherapy was started and initial regimen of LTG was given.Temperature normalization and clinical improvement were quicklynoted.

Conclusion: Several AEDs were suspected to induce hypothermia,including VPA and GBP. TPM was suspected to enhance VPA effect onhypothermia, while LTG was never mentioned. This report suggests thatLTG, as well as TPM, may elicit hypothermia in patients on polytherapy.Clinicians treating such patients should therefore be aware of this treat-able side-effect.

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p650VIGABATRIN ASSOCIATED MOVEMENT DISORDERWITH MRI SCAN CHANGES: AN UNDER-RECOGNI-SED COMPLICATIONM. Kaliakatsos, Y. A. Hernandez Vega, J. U-King-Im, K.Lascelles, and M. LimEvelina Children's Hospital, London, UK

Purpose: To present a case report demonstrating a rare, harmful butreversible side effect of Vigabatrin.

Method: Video-case report

Result: A 10-month-old girl who was on treatment for infantile spasmswith Vigabatrin and Tetracosactide (day 16 of treatment) presented withprogressive lethargy followed by movement disorder, loss of oral feedingskills and left hemiparesis. Her spasms had stopped on day 7 of treatment.Magnetic Resonance Imaging (MRI) on Day 12 of treatment showed sig-nal change within the basal ganglia and brainstem. Repeat MRI scan(Day 16) showed progressive signal change in the deep grey structureswith a GABA peak on MRS and a further EEG showed a grossly enceph-alophatic but no longer hypsarrthmic pattern. A rapidly progressive mito-chondrial cytopathy was considered but all neurometabolicinvestigations including plasma and CSF lactate and muscle respiratorychain enzyme analysis were negative. Vigabatrin was stopped on the day22 of treatment. Over the next few days she started to make a dramaticrecovery. She became more responsive, the abnormal movementsstopped and the left hemiparesis recovered. Another EEG was done 24hafter stopping Vigabatrin showing a significant improvement. An intervalMRI done three months later was normal.

Conclusion: Clinicians treating children with Vigabatrin need to beaware that encephalopathy with severe movement disorder and accompa-nying MRI abnormalities is a potential complication, as not only is thisreversible on stopping VBT but failure to do so could lead to the diagno-sis of a neurodegenerative disorder.

p651EFFECTS OF VALPROATE AND OXCARBAZEPINE ONNEUTROPHILS’ OXIDATIVE METABOLISM AND OXI-DATIVE STRESS IN EPILEPTIC CHILDRENY. Zhang, Y. Wang, M. Zhang, and X. ZhuChildren's Hospital of Fudan University, Shanghai, China

Purpose: This study was carried out to determine the effects of valpro-ate (VPA) and oxcarbazepine (OXC) on neutrophils’ oxidative metabo-lism and oxidant status in epileptic children.

Method: We enrolled 26 patients receiving VPA, 11 receiving OXC and30 sex-and age-matched healthy children. We measured the activationrates of neutrophils by flow cytometry and the serum activities of mye-loperoxidase (MPO) in patients before and after 6 months treatmentrespectively and in all the healthy children. Malondialdehyde (MDA) asan indicator of lipid peroxidation and antioxidant enzymes includingsuperoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase(GSH-Px) were also measured in plasma respectively.

Result: The activation rates of neutrophils in patients treated with VPAor OXC after 6 months were significantly higher than the data of controlgroup (P=0.001 and P=0.003, respectively) and pretreatment (P=0.001and P=0.005, respectively). The plasma MPO activities and levels ofMDA in patients were also higher while the activities of SOD and CATwere lower than the control group and pretreatment. GSH-Px levels did

not differ between the groups. Comparing the VPA with OXC therapy,VPA was associated with higher activation rates of neutrophils and MDAlevels. The serum MDA level was higher in the patients taking antiepilep-tic drugs (AEDs) than pretreatment (P=0.001) and positively correlatedwith the activation rates of neutrophils.

Conclusion: Epileptic children exposed to oxidative stress and AEDschange the oxidative/antioxidative balance. AEDs may activate the neu-trophils of patients and cause oxidative damage.

p652EXTERNAL TRIGEMINAL NERVE STIMULATION(ETNS—) FOR THE TREATMENT OF DRUG RESIS-TANT EPILEPSY: A PHASE II RANDOMIZED CON-TROL TRIALC. Degiorgio*, C. Kealey�, J. Soss*, D. Murray*, S. Oviedo�,D. Markovic*, I. Cook*, and C. Heck�

*University of California – Los Angeles, Los Angeles, CA, USA;�NeuroSigma Inc., Los Angeles, CA, USA; and �University ofSouthern California, Los Angeles, CA, USA

Purpose: External Trigeminal Nerve Stimulation (eTNS) is a novelemerging neuromodulation therapy under investigation for the treatmentof drug resistant epilepsy (DRE) and major depression (MDD). We pres-ent results from the Phase II randomized double-blind control trial ofeTNS for DRE.

Method: 50 subjects with DRE were enrolled at two clinical sites(UCLA and USC) and randomized to receive active eTNS or a controlregimen. Baseline seizure frequency and mood were assessed prior to ini-tiating treatment. Subjects were evaluated at 6, 12, and 18 weeks forchanges in seizure frequency and mood.

Result: 40.5% of subjects receiving active eTNS experienced a ‡ 50%reduction in seizure frequency vs. 15.6% of patients in the active controlat 18-weeks (within group p = 0.02, between groups p = 0.078, GEE).Median seizure frequency was also significantly decreased at 12 weeks,(p = 0.013 at 12 weeks, Wilcoxon signed-rank test). Mood (Beck Depres-sion Inventory) improved significantly from baseline during the acutetreatment period (-8.1 in the treatment group vs. -3.3 in the controls (p =0.02, ANOVA).

Conclusion: In this phase II randomized control trial, eTNS was associ-ated with a significant increase in ‡ 50% responder rate and significantimprovement in mood over the 18-week acute treatment period. Therobust response in both seizures and mood over the treatment period indi-cates that eTNS is a promising and unique new neuromodulation treat-ment modality.

p653CLINICAL PROFILES AND OUTCOME OF PATIENTSWITH ANTIEPILEPTIC DRUG-INDUCED STEVENJOHNSON SYNDROME/TOXIC EPIDERMAL NECRO-SISG. V. L. HamoyPhilippine General Hospital, Ermita, Manila, Philippines

Purpose: This study aims to identify the epidemiological features ofAED-induced SJS/TEN among patients admitted at a tertiary hospital.Specifically, the researchers wanted to describe the clinical profiles ofAED-induced SJS/TEN patients; identify the antiepileptic drugs thatcommonly cause SJS/TEN; and to determine the outcome of patientswho developed the said condition.

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Method: A retrospective review of the cases seen at at a tertiary hospi-tal, with a diagnosis of Steven Johnson Syndrome (SJS) and ToxicEpidermal Necrosis (TEN) during 2002 to 2011 was carried out. A totalof 165 patients were identified with a discharge diagnosis of SJS andTEN according to International Classification of Disease code. Of these,25 patients were selected based on the inclusion criteria of patients whodeveloped antiepileptic dug induced SJS/TEN. The diagnosis of SJS/TEN was based on the findings and diagnosis by dermatologist or aller-gologist. Presence of other pre-existing dermatologic problems such asacneiform growths, seborrheic keratosis, psoriasis, fungal or any super-imposed bacterial infections were excluded in this study. The followingdata were obtained: age, sex, antiepileptic drugs used, dosages and dura-tion of intake, co-medications, co-morbidities, treatment and outcome. Inthis study, we described the population based on the demographic profilecollected. Descriptive statistics such as the mean was used for continuousdata. On the other hand, frequency was used for categorical data. Thisstudy is based on a retrospective analysis.

Result: This study reviewed 165 patients who developed Steven John-son Syndrome and Toxic Epidermal Necrosis with ages ranging from 1 to72 years old. Of these, 25 out of 165 (15%) reported intake of antiepilep-tic drugs, and were included in the study. Out of 25, twenty four patients(96%) developed SJS and only one developed TEN (0.04%). There were14 (56%) men and 11 (44%) women included in the study. The mean ageat diagnosis was 30 years old. Majority of the patients were adults com-prising 72% and 28% were pediatric patients. Figure 1 shows that amongall the patients included in the study, the most common antiepilepticdrugs reported were phenytoin (9 cases, 36%) and Phenobarbital (9 cases,36%). This was followed by carbamazepine (6 cases, 24%), Levetirace-tam (2 cases, 8%), and valproic acid (1 case, 4%). In the adult group, themost common AED used was PHT, while in pediatric group, the mostcommon was PHB. Majority of the patients (22 of 25, 88%) were onmonotherapy, and three patients were given co-medication with a secondantiepileptic drug. The mean duration of intake differed between antiepi-leptic drugs used. For PHB, the mean duration of intake was 23 days,while PHT, CBZ, LEV and VPA were 21 days, 19 days, 63 days and 7days respectively. On the other hand, the mean duration of intake in poly-therapy was 25 days. The earliest time of drug reaction developed after 7days of intake while the longest was in 60 days. Most of the patients weretreated with intravenous corticosteroids. Twenty- two patients improvedfrom the illness, 2 died of sepsis and 1 died of renal failure. These threepatients had complications while admitted. Two of them developed sep-sis and one had multiple electrolyte imbalances. There were six patientswho had other concomitant drugs used during the time they developedSJS and TEN.

Conclusion: We concluded that PHT and PHB are the common AEDsassociated with the development of SJS/TEN among patients seen in atertiary hospital. However, in common practice in this tertiary hospital,PHB is widely used AED among adult and pediatric patients. Most of thepatients who developed AED induced SJS/TEN were middle aged males.One major drawback of this study was the small population of patientswith AED-induced SJS and TEN. Because of this limitation, we were notable to do a multivariable correlation of the risk factors for the AED-induced SJS/TEN. Also the small sample size was not enough to general-ize the results to the population of Filipinos taking AEDs for the firsttime.

p654THE CONSENSUS ON USING AEDS AFTER CRANIO-CEREBRAL OPERATIONS. LiChina Association against Epilepsy, Beijing, China

Purpose: Trying to set up commonly recognized regulation of usingAEDs after the Cranio-cerebral operation to prevent, control of seizures.

Method: The China Association Against Epilepsy (CAAE) organized ataskforce to compile the ‘‘The Consensus on Using AEDs after Cranio-cerebral Operation’’and accepted by the CAAE Board in 2012.

Result: The Consensus includes four parts: 1, Classification of seizuresafter cranio-cerebral diseases and trauma (CCDT) operations and generalprinciples of treatment; 2, CCDT patients without seizure before opera-tion: (1) Indications, methods and duration of using AEDs to ‘‘prevent’’seizures after surgery, (2) Treatment of occurred seizures after operationwith AEDs; 3, CCDT patients who had seizures before operation (theoperation is for treating other brain disease, focal lesions other than epi-lepsy): methods and duration of using AEDS after operation; 4, Emer-gency treatment of seizures (GTCS and/or convulsive status epilepticus)after cranio-cerebral operation. A flow chart for the above-mentioned istabled in the present paper.

Conclusion: ‘‘The Consensus on Using AEDs after Cranio-cerebralOperation’’ has been completed this year to serve as a reference docu-ment for neurosurgeons and neurologists, pediatricians who are dealingwith epilepsy treatment for CCDT patients after brain surgery.

p655THE COMPARISION OF EEG PATTERNS AT THEBACKGROUND OF AEP DRUGS IN EPILEPTICPATIENTSI. Khachidze, V. Maloletnev, and M. GugushviliBeritashvili Centre of Experimental Biomedicine and TatishviliMedical Center, Tbilisi, Georgia

Purpose: Electroencephalography (EEG) is an efficient tool to studyboth benefit and a potential adverse effect of various antiepileptic drugs.Although selection of antiepileptic drugs (AED) depends on type of sei-zures, the general effect of various AED on overall neurophysiologicalstate of CNS is not fully understood. The aim of this study was to assessthe effect of Carbamazepine (CBZ) and Vallproate acid (VPA) on bothan epileptic activity and a general brain activity in epileptic childrenusing EEG technique.

Method: One hyndred and seventeen epileptic patients between 5 and11 years old were examined. Some patients (n=63) received VPA treat-ment, whereas others (n=54) CBZ therapy. The patients underwent EEGrecording three times: before administration of AED, 3–4 months and 6–8 months after the initiation of treatment. The Spectral analysis of theabsolute value of power (AVP) was a studied variable.

Results: VPA reduced the degree of disorganization of basic EEG rhyth-micity of high amplitude mono-poly-morph waves in low frequencyrange, suppressed a spike-wave complex in thalamus and decreased AVPspectra especially in parietal cortex. On the other hand, CBZ therapyincreased AVP dynamics by increasing activity in the low frequencyrange. CBZ mostly affect the neural population of the cortex and predom-inantly occipital cortical areas.

Conclusion: The different effect of VPA and CBZ on the bioelectricalactivity of the brain in epileptic children could be related to the region-specific differences within the loci of maximal neuropharmacologicaleffect of the studied drugs.

p656EFFICACY AND SAFETY OF ONCE-DAILY ADJUNC-TIVE PERAMPANEL, A SELECTIVE AMPA ANTAGO-NIST: A POOLED ANALYSIS OF THREE PHASE IIITRIALS IN PATIENTS WITH TREATMENT-RESIS-TANT PARTIAL-ONSET SEIZURESE. Ben-Menachem*, G. L. Krauss�, S. Noachtar�,J. M. Serratosa§, D. Squillacote–, H. Yang–, J. Zhu–, andA. Laurenza–

*University of Gothenburg, Gothenburg, Sweden; �JohnsHopkins University, Baltimore, MD, USA; �University of

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Munich, Munich, Germany; §Hospital UniversitarioFundaci�n Jim�nez Diaz and CIBERER, Madrid, Spain; and–Eisai Neuroscience Product Creation Unit, Woodcliff Lake,NJ, USA

Purpose: Perampanel was evaluated in three pivotal phase III trials.Results from the separate trials have been presented previously; here, weanalyzed the pooled efficacy and safety results across the three studiesaccording to the actual doses of perampanel achieved.

Method: Patients (‡12 years with uncontrolled partial-onset sei-zures) were randomized to double-blind placebo, perampanel 2, 4, 8,12 mg/day. Percent change in seizure frequency/28 days and 50%responder rate were primary endpoints. Efficacy analyses in thisreport were based on actual (last) doses received at the end of thedouble-blind phase by completer patients (excluding Central/SouthAmerican patients due to significant treatment-by-region interac-tions). Safety analyses included all treated patients who had safetyassessments.

Result: Overall, 442, 180, 172, 431, and 255 patients were included inthe safety population for placebo, perampanel 2, 4, 8, 12 mg (randomizeddose), respectively. 348, 161, 159, 46, 287, 14, 114 patients completedthe study on a last dose of placebo, perampanel 2, 4, 6, 8, 10, 12 mg. Med-ian percent changes in seizure frequency for placebo, 2, 4, 8, 12 mg were-11.7%, -17.3%, -24.1%, -31.9%, -26.2%, respectively. Responder rateswere 18.4%, 22.4%, 30.8%, 37.6%, and 39.5%. These data are compara-ble with randomized results from the individual studies, which did notaccount for failure to reach assigned doses. Safety analyses were alsocomparable.

Conclusion: Perampanel efficacy and safety are further demonstrated inactual dose analyses of the entire phase III program population. Support:Eisai Inc

p657EFFECTIVENESS AND TOLERABILITY OF LEVETI-RACETAM IN CHILDREN UNDER 2 YEARS OF AGEG. A. Ramos-Rivera, M. Kolnikova, A. Blahova-Vicenova,D. Kovarova, J. Payerova, and P. SykoraChildren¢s University Hospital, Bratislava, Slovak Republic

Purpose: To assess the effectiveness and tolerability of levetiracetam(LEV) as add-on therapy in the treatment of epilepsy in children less than2 years of age.

Method: Retrospective evaluation of treatment with LEV in a cohort of26 children aged 2–22 months (mean 11.7 months). Treatment was con-sidered effective if the reduction of seizures reached ‡50%. The groupconsisted of children hospitalized and followed-up in the Department ofPediatric Neurology in Children¢s University Hospital in Bratislava fromJanuary 2009 to December 2011. The mean dose of LEV was 37.3 mg/kg/d (range 16.5–50.0 mg/kg/d), the average number of antiepilepticdrugs used before LEV was 2.1 (1–6 drugs). Mean follow-up time was7.8 months (range 0.1–26.0 months).

Result: Of the 26 children, LEV was effective in 7 patients (26.9%),two of whom were seizure-free (8.7%). LEV was ineffective in 15 chil-dren (57.7%) and in one patient (4.4%) the number of seizuresincreased. Generalized seizures were present in 10 patients (38.5%). Intwo of them LEV was effective (20.0%). Partial seizures occurred in 17patients (43.5%). LEV was effective in 6 of these children (35.3%).Two patients of the whole cohort present both partial and generalizedseizures. No effect was observed in one patient with reflex atonic sei-zures, one child with epilepsia partialis continua and one with malignantmigrating epilepsy. LEV was discontinued for adverse reactions in 3children (11.5%).

Conclusion: LEV was more effective in the treatment of partial sei-zures compared with generalized. LEV was well tolerated by ourpatients.

p658A NOVEL ANTICONVULSANT ISOXYLITONES [E/Z]SUPPRESSES SODIUM CURRENTS IN NAV1.2 ANDNAV1.3, AND PROLONGS INACTIVATION DEVELOP-MENT AND RECOVERY FROM INACTIVATION INVOLTAGE-GATED SODIUM CHANNELSM. N. Ashraf*, S. U. Simjee�, and M. O. Poulter**Robarts Research Institute, London, ON, Canada; and�International Center for Chemical and Biological Sciences,Karachi, Pakistan

Purpose: Epilepsy remains a major medical challenge and till to dateis not completely curable and more than 30% patients worldwide arestill living with refractory epilepsy. The roots of the plant Delphiniumdenudatum indigenous to the Himalayas and Kashmir had beenreported to be used in treating seizures by local folk medicine practi-tioners. Although, the extracts / fractions prepared from the aforemen-tioned plant have been previously studied in acute seizure models, thepurified, patented compound (Patent No. 7,399,888 B2) named Iso-xylitones ([E/Z]-2-propanone-1,3,5,5-trimethyl2-cyclohexen-1-ylidine)have not been characterized for its mechanism of action.

Method: We have carried out patch clamp and electrophysiologystudies in order to explore the mechanism of action and dose-response curve of this novel anticonvulsant compound both in vitroand in vivo.

Result: Voltage-clamp studies showed that isoxylitones suppressedsodium current (INa) in Nav1.3 in a concentration-dependent manner withIC50 value of 185 nM in cultured rat cortical neurons (pyramidal and in-terneurons). The presence of 185 nM isoxylitones not only prolonged therecovery of sodium channels from inactivation with the time constant s18.7 ms as compared to control recordings with s 9.4 ms, but also signifi-cantly altered the voltage dependence of inactivation development byshifting the Boltzmann sigmoidal curve to the more hyperpolarizedpotentials. Moreover, isoxylitones inhibited INa in Nav 1.2 with IC50 val-ues of 185 nM and 200 nM in naive and electrically kindled cortical neu-rons in rat brain slices, respectively.

Conclusion: Thus, isoxylitones is now a potential candidate to be devel-oped as a future anti-epileptic drug (AED).

p659EFFICACY OF DIFFERENT LAMOTRIGINE DOSAGEREGIMENS IN EPILEPETIC PATIENTS’ – CLINICALEXPERIENCER. GiladE Wolfson Med Center, Holon, Israel

Purpose: Lamotrigine is an effective and rather innocuous drug used ina large spectrum of epileptic disorders for monotherapy. Yet the optimaldose of lamotrigine when given as monotherapy has still to be deter-mined. In pivotal studies, the daily dose recommended is 200 mg. Clini-cal experience accumulated during the last two decades shows that thisdaily dosage is not sufficient in many cases to achieve seizure freedom.Then again, doses twice as high do not increase significantly the drug tox-icity. The purpose of the present study is to evaluate the clinical outcomeon a population of epileptic patients treated at first with an average dailydose of 200 mg lamotrigine and then with the range of doses needed toachieve seizure freedom, or if these patients still experience seizures,were they switched to another medication? And what was their outcome?.The study is to include evaluating the influence of real life experiences,often quite different from RCT study conclusions, and the dosage regi-

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men recommended by pivotal studies for being the ideal one for thispatient population.

Method: This is a retrospective study monitoring the records of all theadult patients, who were treated with lamotrigine as monotherapy for sei-zures, at two epilepsy clinics. All these patients treated at a dosage of 200mg for at least three months were included in the study. Data includedtype of seizures, disease duration, therapy duration and seizure frequency(if the patient was not seizure-free). These patients, who suffered frombreakthrough seizures or had to change their AED, were categorized andstatistically evaluated separately.

Result: Until now, a 100 adult patients’ records were reviewed andalmost one-half of the patients were not free of seizures while being trea-ted with lamotrigine 200 mg per day as monotherapy. About 50% of thesepatients needed a higher dose of lamotrigine for stopping the seizures,and about 30%, needed to change treatment.

Conclusion: It may be necessary to consider starting a daily dose higherthan 200 mg of lamotrigine from the beginning, instead of having tourgently raise the dosage only after the patient experienced breakthroughseizures.


p660LOW DOSE LACOSAMIDE-INDUCED ATRIAL FIBRIL-LATION: CASE ANALYSIS WITH LITERATUREREVIEWK. R. Kaufman, A. E. Velez, S. Wong, and R. ManiUMDNJ-Robert Wood Johnson Medical School, NewBrunswick, NJ, USA

Purpose: Lacosamide (LCM) is a novel anti-epileptic drug (AED)approved by the FDA for adjunctive treatment of partial epilepsy withand without secondary generalization. LCM selectively modulates volt-age-gated sodium channels. AED selection is related to both efficacy andadverse effect profile. Dose-dependent LCM-induced cardiac arrhyth-mias have been reported. This case represents the first instance of lowloading dose LCM-induced atrial fibrillation.

Method: Case analysis with literature review.

Result: A 67 year-old woman with a history of complex partial sei-zures, peri-menstrual migraines, and multiple myeloma was admittedfor autologous bone marrow transplant. This patient had no knownprior cardiac disease. Admission medications included methylprednis-olone, clotrimazole, fluconazole, acyclovir, neupogen, ondansetron,pantoprazole, loperamide, calcium phospate, and primidone. Renaland hepatic function was normal. During her admission, episodes ofstaring with oral/facial automatisms increased in frequency and dura-tion (multiple events/hour). The patient did not respond to additionof levetiracetam (1500mg bid) and continuous video-EEG was initi-ated to characterize her seizure activities. Multiple epileptic eventswere recorded within four hours on video-EEG. LCM was initiatedwith 200mg intravenous infusion, at the end of which an irregularlyirregular rhythm was noted on telemetry. Asymptomatic atrial fibril-lation lasted for two hours with spontaneous resolution. Atrial fibril-lation onset correlated to the theoretical time of maximum LCMplasma concentration. LCM was discontinued.

Conclusion: Low loading dose LCM may provoke atrial fibrillation.Neurologists and internists need to be cognizant of this potential adverseeffect. Cardiac monitoring may be required with LCM dose rapid titra-tion, especially if given intravenously.

p661ADJUNCTIVE LACOSAMIDE IN PATIENTS WITHUNCONTROLLED FOCAL EPILEPSY: INTERIM ANAL-YSIS OF A PROSPECTIVE AUDITK. Kelly, L. J. Stephen, P. Parker, and M. BrodieWestern Infirmary, Glasgow, UK

Purpose: This prospective audit explores outcomes with adjunctive la-cosamide (LCM), a novel sodium channel blocker, in everyday clinicalpractice.

Method: To date, 127 of 150 patients (73M; 77F, 18–74 years [median42 years]) with uncontrolled partial-onset seizures + secondary general-isation (monthly frequency 1–300; [median 4]) have reached an endpoint.They received mostly one (range 1–4) antiepileptic drugs (AEDs), havingpreviously tried 1–12 schedules (median 2). After 12 weeks on stabledosing, LCM was added and titrated as necessary.

Result: Seizure freedom was achieved in 30 (24%) patients (medianLCM dose 100mg/day, range 50–500mg/day). Seven received LCM withsodium channel blockers, 19 with other mechanisms, and 4 controlled onLCM monotherapy. Patients were more likely to become seizure-freewhen LCM was used as first add-on (26 of 83, 31.3%), compared to latertreatment (4 of 44, 10.3%; p=0.005). Twenty-five (19%) patients wereclassified as responders (>50% seizure reduction versus baseline) with43 (34%) demonstrating marginal benefit. LCM was withdrawn in 29(23%) patients (11 lack of efficacy, 18 side-effects). Commonest prob-lems included nausea, vomiting, sedation, headache, diplopia, dizziness,tremor, ataxia and rash. More patients taking sodium valproate (14 of 34)discontinued LCM compared to other AEDs (20 of 102; p=0.012), partic-ularly due to side-effects (11 of 34 on valproate vs 10 of 102 on otherAEDs; p=0.002).

Conclusion: Adjunctive LCM was effective and well-tolerated what-ever the baseline treatment. Seizure freedom was more likely when LCMwas used a first add-on. Patients taking valproate were more likely to dis-continue LCM.

p662DIAGNOSTICS AND THERAPEUTICASPECTS OFRESISTANT EPILEPTIC SEIZURES IN CHILDREN OFEARLY AGE WITH A TUBEROUS SCLEROSISL. G. Kirillova*, L. I. Tkachuk�, A. A. Shevchenko*,V. V. Lysytsa*, and L. Y. Sylaeva**Institute of Pediatrics, Obstetrics and Gynecology, Kiev,Ukraine; and �Pediatrics, Obstetrics and Gynecology, Kiev,Ukraine

Purpose: optimization of early diagnostics and treatment of resistantepileptic attacks in children with a tuberous sclerosis.

Method: During the last 7 years there were studied 9 children with atuberous sclerosis in an age category to 3 years. On the basis of magneticresonance tomography, for all nine children there were determined ham-artomas from 3 to 30 millimetres in the different areas of the brain. Therewere discovered rabdomyomas in 3 children in a term 35–37 weeks ofpregnancy intrauterinely. In spite of focal lesions of brain structures, inall children were noticed generalized tonic-clonic seizures (resistant)from 5 to 10 a day. During the treatment of Topamax (to 10 mg/kg), fre-quency of attacks decreased, however, there was no control. Apart fromanticonvulsants (Topamax) the children started to receive the preparationVigabatrin (from 40 to 100 mg/kg).

Result: Combination of anticonvulsive therapy led to the decrease in thenumber of attacks in 4 children from 1 attack in a day to 1 attack in amonth. In 5 children attacks were halted.

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Conclusion: This work stresses the necessity of timely magnetic reso-nance tomografy and combination of Topamax and Vigabatrin for opti-mization of treatment of resistant epileptic attacks in children with atuberous sclerosis.

p663DESIGN OF AN OPEN-LABEL, MULTICENTRE, NON-INTERVENTIONAL STUDY OF ZONISAMIDE ASFIRST-LINE ADJUNCTIVE TREATMENT IN ADULTSWITH PARTIAL EPILEPSY: THE ZOOM STUDYM. Baulac*, F. Rugg-Gunn�, and I. Chouette�

*Neurology Hpital Piti�-SalpÞtri�re, Paris, France; �TheNational Hospital for Neurology and Neurosurgery, London,UK; and �Eisai Europe Limited, Hatfield, UK

Purpose: Zonisamide (ZNS), a benzisoxazole derivative chemicallyunrelated to other antiepileptic drugs (AEDs), is currently licensed foradjunctive treatment of adults with partial seizures (with or withoutsecondary generalisation). Whilst clinical trials of adjunctive AEDtherapies are required for regulatory purposes, they do not necessarilyreflect real-life practice, since conducted under standardised condi-tions in carefully selected, highly refractory populations. The purposeof this study is to assess retention rate, efficacy and tolerability ofzonisamide when used as first-line adjunctive treatment in adults withless refractory partial epilepsy, under everyday clinical practice condi-tions.

Method: ZOnisamide in partial-onset seizures with One AED as base-line Medication (ZOOM) is a prospective, international, open-label, non-interventional study that will enrol adults with partial-onset seizures,insufficiently controlled with AED monotherapy, for whom the treatingphysician has decided to initiate adjunctive ZNS therapy. ZNS treatmentwill be commenced according to license. Patients will be seen at baselineand then according to normal clinical practice over 6-7 months. Studyassessments will be conducted at baseline and after 3 and 6 months. Pri-mary endpoint will be 6-month retention rate. Other assessments willinclude seizure control, adverse events and quality of life. Dosing infor-mation will also be collected.

Result: The study is expected to enrol approximately 700 patients from200-250 centres in 9 European countries. Recruitment is expected tocommence March 2012; study is expected to complete end of 2013.

Conclusion: ZOOM will provide valuable information on ZNS as first-line adjunctive treatment under conditions of everyday clinical practice.Supported by Eisai

p664HYPERHOMOCYSTEINEMIA IN EPILEPTIC PATIENTSM. Candrlic, R. Susak, and S. JuricClinical Hospital Center Osijek, Osijek, Croatia

Purpose: Antiepileptic drugs (AEDs) may induce supraphysiologicalplasma concentrations of total (t) homocysteine (Hcy). Moderate hype-rhomocysteinemia (HHcy) is risk factor for cardiovascular disease.Guidelines recommend a target plasma t-Hcy level of < 10 umol/l. Theaim of the present study was to asses frequancy of HHcy in epilepticpatients and to investigate the effect of AEDs on plasma tHcy levels.

Method: We surveyed a total of 57 epileptic patients (age range 19 – 81years, mean age 44.8 +- 14.5 years). On AEDs mononotherapy was 17(29.8%) patients and on polytherapy 40 (70.2%), with no other knowncause of HHcy. The median duration of therapy was 16 years. PlasmatHcy, folic acid (FA) and vitamin B12 were determined in all patients.

Results: Showed eleveted plasma tHcy levels (tHcy > 15micromol/l) in25 (44%) patients . Even 51 (89.5%) patients had values more than it isrecommended, statistically significant in patients on polytherapy (p=0.002) than on monotherapy. Serum FA levels were lower in 40 (70%)patients, esspecially in patients with longer duration of therapy and inthose on polytherapy. Statistically significant differences for both para-metars were found in patients using carbamazepin and phenobarbital thanin patients using other AEDs (p< 0.005). Mean velue of vitamin B12 wasnormal in majoriti of patients.

Our study confirmed high frequency of HHcy in epileptic-patients andsuggested that carbamazepin and phenobarbital play major role in devel-opment of HHcy. Adding folate and vitamin B12 to every day AED ther-apy is safe way of reducing risk of HHcy.

p665DESIGN OF THE EPOS STUDY: AN OPEN-LABEL,MULTICENTRE, NON-INTERVENTIONAL STUDY TOEVALUATE ESLICARBAZEPINE ACETATE ASADJUNCTIVE TREATMENT TO ONE BASELINE AN-TIEPILEPTIC DRUG IN ADULTS WITH PARTIAL-ONSET SEIZURESM. Holtkamp*, C. Lawthom�, and I. Chouette�

*Charit� – Universittsmedizin, Berlin, Germany; �AneurinBevan Health Board, Gwent, UK; and �Eisai Europe Limited,Hatfield, UK

Purpose: Eslicarbazepine acetate (ESL) is a once-daily voltage-gatedsodium channel blocker that was approved in Europe in 2009 asadjunctive therapy in adults with partial-onset seizures, with or withoutsecondary generalisation, based on an initial proof-of-concept Phase IItrial and three subsequent Phase III trials. This non-interventional studyaims to increase the knowledge about ESL's effectiveness and tolerabil-ity in routine clinical practice, when used to treat adult epilepsypatients who are less refractory than those included in Phase III adjunc-tive clinical trials.

Method: The Eslicarbazepine acetate in Partial-Onset Seizures study(EPOS) is a prospective, multicentre, open-label, non-interventionalstudy involving adults with partial-onset seizures insufficiently con-trolled with AED monotherapy, for whom the treating physician has pre-viously decided it was in the patient's best interest to be initiatedadjunctive ESL, according to its license and Summary of Product Charac-teristics. Patients will be seen at baseline and then according to normalclinical practice, over a follow-up period of 6–7 months. Study assess-ments will be conducted at baseline and after 3 and 6 months. Primaryendpoint will be 6-month retention rate. Other assessments will includeseizure frequency, adverse events and quality of life.

Result: EPOS is expected to enrol approximately 800 patients from‡200 centres in Denmark, France, Germany, Norway, Sweden and UK.Recruitment is expected to commence March 2012 and the study isexpected to complete end of 2013.

Conclusion: EPOS will provide a better understanding of the use ofESL as early adjunctive therapy in a clinical practice setting. Supportedby Eisai

p666COMPARATIVE EFFICACY OF COMBINATION DRUGTHERAPY IN REFRACTORY EPILEPSYN. P. Poolos*, L. N. Warner*, S. Z. Humphreys�, andS. Williams�

*University of Washington, Seattle, WA, USA; �Fircrest RHC,Shoreline, WA, USA; and �Rainier RHC, Buckley, WA, USA

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Purpose: We sought to determine whether any AED, in monotherapy orin combination, produced superior efficacy in medically refractory epi-lepsy by retrospectively analyzing an extensive database of AED therapyof severely developmentally disabled adults with epilepsy.

Method: We obtained records charting monthly seizure frequencyand AED treatment for 168 patients and analyzed 140 € 5.8 (mean€ SEM) months of data for each patient, calculating the averageseizure frequency during each unique AED regimen consisting of 1,2, or 3 drugs in combination from a list of 8 consisting of (in orderof frequency of exposure using standard acronyms): LTG, VPA,CBZ, PHT, TPM, LEV, GBP, and ZNS. We then made within-patient comparisons of the ratio of seizure frequencies with differentregimens.

Result: For patients on duotherapy, average seizure frequency was 0.81that of monotherapy, a 19% decrease. However seizure frequency withthree drugs at a time was 1.07 that on duotherapy, demonstrating no addi-tional benefit.

In comparison of individual AED regimens against a aggregate aver-age of all other regimens, only the combination of LTG/VPA showedsuperior efficacy (seizure frequency 0.52 of the average) out of 32 regi-mens. In head-to-head comparisons, LTG/VPA was superior to six otherregimens, constituting the majority of 10 statistically significant compar-isons.

Conclusion: These results suggest that LTG/VPA uniquely shows supe-rior efficacy in medically refractory epilepsy. These results may suggestfuture prospective trials to confirm the superiority of LTG/VPA, and tobetter understand the underlying mechanisms of its action.

p667LACOSAMIDE IN ADD ON THERAPY TO TREAT PAR-TIAL EPILEPSIESO. Daniele*, L. Zummo*, L. Urso�, B. Fierro*, and E. Natal�**Palermo, Italy; and �Department of Experimental Biomedicineand Clinic Neurosciences University of Palermo, Palermo, Italy

Purpose: Lacosamide is a new molecule which has a marked anticon-vulsant activity in partial epilepsy with or without secondary generaliza-tion. Aim of the present study is to evaluate tolerability,pharmacokinetics, pharmacodynamics and efficacy of lacosamide whenused in association with old and new AEDs.

Method: About 30 patients referred to our Center for Diagnosis andTreatment of Epilepsy of the University of Palermo were enrolled suffer-ing from partial epilepsy on bi-polypharmacy. Mean age was 36.6 years,mean age at onset was 15,9 25 patients had intractable epilepsy and73.3% showed reduction of seizures after 6 months of therapy since addi-tion of lacosamide (doses from 200 to 400 mg/die).

Result: Our data show a statistically significant association between ageat onset of seizures and drug resistance (p < 0.0038) but not between thislatter and mean duration of the disease, as well as between reduction ofthe frequency of seizures and age at onset or between the type of bi-poly-therapy.

Conclusion: Our data indicate that, so far, there is not possible to estab-lish the pharmacodynamic and pharmacokinetic mechanism explainingthe significant reduction of seizures in patients with lacosamide on add-on. Data of the literature suggest that synergism and antagonism arerelated to various factors such as number of administered drugs, relativemechanism of action, posology, titration which therapeutic resultsdepend on. Facility of administration, tolerability and therapeutical effi-cacy of lacosamide make it an interesting drug in the treatment of focalpharmacoresistant epilepsies even if further studies are needed to evalu-ate its interactions with other AEDs.

p668COST OF ANTIEPILEPTIC DRUG MONOTHERAPIESAND COMBINATION THERAPIES AT A TERTIARYREFERRAL HOSPITAL IN SINGAPORES. Lim*, S. See�, P. Wong�, and S. Lim�

*Nanyang Technological University, Singapore, Singapore;�National Neuroscience Institute & Singapore General Hospital,Singapore, Singapore; and �Singapore General Hospital,Singapore, Singapore

Purpose: Antiepileptic drug (AED) cost contributes significantly to eco-nomic burden of patients and society. We investigate how costly are (1)Newer AEDs (NAEDs) compared to Conventional AEDs (CAEDs) and(2) combination therapies compared to monotherapies at a tertiary refer-ral hospital in Singapore.

Method: AED prescription patterns of 682 patients seen by a neurolo-gist from January 2008 to December 2011 were used to calculate AEDcost. CAEDs have been available in Singapore for >20 years (Carbamaz-epine, Phenytoin, Valproate, Phenobarbitone, Clonazepam, Clobazemand Primidone) whereas NAEDs are available for <20 years (Lamotri-gine, Gabapentin, Topiramate, Levetiracetam and Pregabaline). Theywere prescribed mainly based on patients’ seizure type(s), AED side-effect profile and/or potential for drug-interaction. Dosages were opti-mised based on seizure control and tolerability. Total AED cost per yearto the patients is calculated according to number, type and dosages ofAED(s) in their last prescription.

Result: 354 (51.9%) patients were on monotherapies (CAEDs: 253; NA-EDs: 101) and 328 (48.1%) were on combination therapies (CAEDs only:118; CAEDs plus NAEDs: 194; NAEDs only: 16). Cost of CAED mono-therapies is 20–797 EUR/year (median: 126 EUR/year) and NAEDmonotherapies is 229–3083 EUR/year (1088 EUR/year). Cost of combi-nation therapies with CAEDs only is 123–1208 EUR/year (median: 511EUR), CAEDs plus NAEDs is 390–8271 EUR/year (1992 EUR) and NA-EDs only is 1274–8410 EUR/year (3426 EUR).

Conclusion: NAEDs are substantially more costly than CAEDs. Theirinclusion in combination therapies further increases the economic burdenof epilepsy care. These might lead to unsustainable long-term NAEDusage and sub-optimal seizure control.

p669ANALYSIS OF SEIZURE FREQUENCY REDUCTION BYCONCOMITANT ANTIEPILEPTIC DRUG (AED) USEWITH ADJUNCTIVE PERAMPANEL: POOLED PHASEIII RESULTSE. Trinka*, H. Straub�, D. Squillacote�, H. Yang�, D. Kumar�,and A. Laurenza�

*Paracelsus Medical University, Salzburg, Austria;�Epilepsieklinik Tabor, Bernau, Germany; and �EisaiNeuroscience Product Creation Unit, Woodcliff Lake, NJ, USA

Purpose: To examine seizure frequency reduction with the 5 most fre-quent concomitant AEDs in the pooled perampanel epilepsy phase III tri-als (304/305/306).

Method: Patients ‡12 years experiencing treatment-resistant partial-onset seizures despite 1–3 concomitant AEDs were randomized toonce-daily, double-blind placebo or perampanel (2, 4, 8 or 12 mg).Analysis of the median percent reduction from Baseline in seizurefrequency/28 days by last dose in patients who completed the Main-tenance Period (actual dose analysis) was performed for patientsconcomitantly receiving any one of the 5 most commonly-used

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AEDs (carbamazepine [n=428], valproate [n=419], lamotrigine[n=397], levetiracetam [n=370], and oxcarbazepine [n=233]) as partof their regimen.

Result: Median changes from Baseline in seizure frequency for the 5most common concomitant AEDs are provided for placebo, 4, 8, 12 mg,respectively (all dose results to be included in poster). Carbamazepine: -13% (n=128), -24% (n=49), -30% (n=116), -18% (n=65). Valproate: -18% (n=128), -28% (n=69), -31% (n=94), -26% (n=31). Lamotrigine: -13% (n=112), -25% (n=64), -33% (n=113), -37% (n=36). Levetiracetam:-18% (n=116), -19% (n=46), -31% (n=92), -39% (n=46). Oxcarbazepine:-5% (n=80), -36% (n=24), -32% (n=54), -38% (n=21). 50% responderrates for each of the 5 AEDs were generally consistent with the medianpercent changes and will be presented in the poster.

Conclusion: Pooled analysis for the 5 most commonly-used concomi-tant AEDs was performed by actual doses in patients taking 1–3 AEDs inthe phase III perampanel trials. Patients generally received increased ben-efit from increased doses of perampanel, as previously demonstrated inPK/PD analyses. Support: Eisai Inc.


p670EVENT-RELATED POTENTIALS IN PATIENTS WITHEPILEPSY TREATED WITH LEVETIRACETAMW. J. DerkowskiPanstwowa Medyczna Wy_zsza Szkola Zawodowa, Kluczbork,Poland

Purpose: The aim of this study was to assess the impact of leveti-racetam dose on event-related potentials (ERP) in patients with epi-lepsy. ERPs are evoked potentials which are obtained by computer-averaging of the electroencephalographic activity in response tostimuli involving cognitive processes of the brain (Duncan C et al.Clinical Neurophysiology 2009; 120:1883–1908). Levetiracetam isan important new generation antiepileptic drug, especially effectivein epilepsy with partial seizures and secondarily generalized partialseizures.

Method: The research material consisted of ERP studies performed in20 patients before and after increasing the dose of levetiracetam duringroutine treatment of epilepsy. In this study, the ERPs had been generatedin response to visual stimuli presented by a proprietary protocol includingappearing alternately with two different frequency geometric patterns.Patients had performed the ERP study at least twice: during a routine lev-etiracetam therapy of epilepsy and after at least two times increase indose, due to insufficient effect of treatment history. All patients were alsoperformed imaging studies (CT or MRI) of the brain and EEG repeatedly,which in addition to the routine analysis were subjected to computer lin-ear analysis (Derkowski W, Kedzia A. Computer analysis of EEG activ-ity in patients with epilepsy treated with levetiracetam in ‘‘TheComputer-Aided Scientifical Research ‘‘, Wroclaw Scientific Society,2008,233–238).

Result: The results obtained evidence of a dose effect of levetiracetamon latency, morphology and amplitude of P300 wave. The paper dis-cusses the importance of the results for the assessment of cognitive func-tion in patients during therapy.

Conclusion: ERPs allow us to monitor the efficiency of cognitive pro-cesses in patients with epilepsy. They are an objective test, based on ananalysis of electrical brain activity and subjective effects of the patientfor the results are very limited.

p671STEADY-STATE PLASMA AND CEREBROSPINALFLUID PHARMACOKINETICS OF ESLICARBAZEPINEACETATE AND OXCARBAZEPINE IN HEALTHY VOL-UNTEERST. Nunes*, J. F. Rocha*, A. Falc¼o�, L. Almeida�, and P. Soares-Da-Silva§

*BIAL – Portela & Ca. SA, S¼o Mamede do Coronado,Portugal; �Health Consulting, Cantanhede, Portugal;�University of Aveiro, Aveiro; and §University of Porto, Porto,Portugal

Purpose: To evaluate the pharmacokinetics of once-daily eslicarbaze-pine acetate (ESL) and twice-daily oxcarbazepine (OXC) and theirmetabolites in cerebrospinal fluid (CSF) and plasma following repeatedoral administration.

Method: Single-center, open-label, randomised, parallel-group study inhealthy volunteers. Volunteers in ESL group (n=7) received 600 mg onDays 1–3 and 1200 mg on Days 4–9, once-daily. Volunteers on OXCgroup (n=7) received 300 mg on Days 1–3 and 600 mg on Days 4–9,twice-daily. Plasma and CSF sampling was performed following lastdose.

Result: Eslicarbazepine was the major drug entity in plasma and CSF,accounting for, respectively, 93.84% and 91.96% of total exposure in theESL group and 78.06% and 76.42% in the OXC group. The extent ofexposure to drug entities R-licarbazepine and oxcarbazepine was approx-imately 4-fold higher with OXC as compared with ESL. There was rela-tively little fluctuation from peak to trough (ratio) in the CSF for botheslicarbazepine (1.5 and 1.2 following ESL and OXC, respectively) andR-licarbazepine (1.2 following either ESL or OXC). In contrast ox-carbazepine showed larger differences between peak and trough (3.1 and6.4 following ESL and OXC, respectively). A total of 45 and 18 treat-ment-emergent adverse events (TEAEs) were reported with OXC andESL, respectively.

Conclusion: In comparison to OXC, administration of ESL resultedin more eslicarbazepine, less R-licarbazepine and less oxcarbazepinein plasma and CSF, which may correlate with the tolerability profilereported with ESL. The apparent smaller peak-trough fluctuation ofeslicarbazepine in CSF than in plasma support once-daily dosing ofESL.

p672EVALUATION OF THE TOLERABILITY OF ADJUNC-TIVE RETIGABINE/EZOGABINE DURING THE REC-OMMENDED TITRATION SCHEDULE IN ADULTSWITH PARTIAL-ONSET SEIZURESN. Brickel*, S. Derossett�, S. Mcdonald�, T. Cyr�, V. Nohria�,and B. Adams�

*GlaxoSmithKline, Uxbridge, UK; �GlaxoSmithKline, ResearchTriangle Park, NC, USA; and �Valeant Pharmaceuticals NorthAmerica, Durham, NC, USA

Purpose: Retigabine/ezogabine 600–1200mg/day is effective as adjunc-tive therapy in adults with partial-onset seizures. Placebo-controlled tri-als utilized a titration schedule starting at 300mg/day (TID), with 150mg/day weekly increases to reach the lowest recommended effective dose of600mg/day after 2 weeks. Tolerability of this recommended startingdose/titration schedule of retigabine/ezogabine versus placebo isevaluated.

Method: Data from placebo-controlled Studies 205, 301(NCT00232596), and 302 (NCT00235755) were integrated to evaluate

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each titration step for overall incidence of adverse events (AEs), seriousAEs (SAEs), AEs leading to withdrawal, and the most common AEsreported in the trials.

Result: Subjects included at each placebo titration step were 300mg/day=427, 450mg/day=418, and 600mg/day=411, and for retigabine/ez-ogabine 300mg/day=813, 450mg/day=793, and 600mg/day=774. Inci-dences were numerically higher for retigabine/ezogabine versusplacebo, respectively, for AEs (300mg/day=33% versus 26%; 450mg/day=25% versus 19%; 600mg/day=27% versus 17%) and AEs leadingto withdrawal (300mg/day=5% versus 3%; 450mg/day=4% versus<1%; 600mg/day=6% versus 1%). Incidence of SAEs for retigabine/ezogabine and placebo were similar: 300mg/day=1% versus <1%;450mg/day=1% versus <1%; 600mg/day=<1% versus <1%. Of themost commonly reported AEs in the placebo-controlled trials, dizzi-ness, somnolence, and fatigue were more frequent with retigabine/ez-ogabine than placebo at each titration step, but incidences weresimilar for headache, confusional state, tremor, abnormal coordination,and blurred vision.

Conclusion: In this analysis, the recommended starting dose and titra-tion schedule of retigabine/ezogabine 300mg/day (TID) with 150mg/dayweekly increments enables adults with partial-onset seizures to reach the600mg/day effective dose within 2 weeks of initiating adjunctive therapywith acceptable tolerability.

Supported by Valeant Pharmaceuticals International and Glaxo-SmithKline.

p673SPIRONUCLEUS LINKED GABA DERIVATIVES ASPOTENTIAL ANTIEPILEPTIC AGENTS ACTINGTHROUGH GABA MEDIATION AND INHIBITINGNITRIC OXIDE AND FREE RADICALSY. Perumal, S. Dharmarajan, and S. K. ReddyBirla Institute of Technology & Science-Pilani, Hyderabadcampus, Hyderabad, India

Purpose: As spiro nucleus serve as privilege compound, we investigatedthe hybridization of this nucleus with GABA nucleus to improve theblood brain penetration and bio-activity as anti-epileptics.

Method: The synthesized compounds were evaluation in a battery of an-ticonvusant animal models that include maximal electroshock seizureand subcutaneous chemical-induced models of picrotoxin, pentylenetet-razole and strychnine models. All the compounds were also tested in neu-rotoxicity models. The doses employed were 30, 100 and 300 mg/kg. Theprotocol was approved by the Institutional Animal Ethical Committee.Mechanistic studies were also performed to confirm the potential ofGABA derivatives on GABA-A receptor using electrophysiology andother mediators studied were those of the levels of nitric oxide and freeradicals using spectrophotometer.

Result: The synthesized compounds exhibited potential anticonvul-sant property in more than 2 animal models of seizure with less or noneurotoxicity compared to standard drugs like phenytoin and carba-mazepine. Compounds SH-3, 8 10 and 14 showed potency in lowerdoses of 10 and 30 mg/kg with no neurotoxicity at the highest dosetested (300 mg/kg). In the mechanistic studies, two representativecompounds were evaluated for GABAergic mediation using contrac-tion per se and in the presence of GABA antagonist bicuculline. TheEC50 of the most active compound (SH-8) tested was 0.38 micromo-lar. the concentration of nitric oxide in brain was significantly reducedwith compounds SH-8 and 14 and the antioxidant activity was alsoencouraging.

Conclusion: Based on the project results, it can be concluded that N-spiro linked GABA emerges as multifunctional derivatives effective forthe treatment of various forms of epilepsy.

p674INTENSE PHARMACOVIGILANCE IN PEDRIATICPATIENTS WITH FOCAL EPILEPSY TREATED WITHCARBAMAZEPINE MONOTHERAPYB. Rodriguez, C. Medina, and J. LopezFoundation Central League Against Epilepsy, Bogota, Colombia

Purpose: To identify, evaluate, and propose a strategy of solutions forthe effectiveness and security problems that pediatric patients show withfocal epilepsy diagnosis and treated with carbamazepine monotherapy.

Abstract: The clinical effects of carbamazepine as monotherapy inpatients with focal epilepsy would be evaluated through a descriptiveobservational cross-section study.

Materials and Methods: A descriptive observational cross sectionstudy. Inclusion criteria: Children with focal epilepsy diagnosis between5 to 15 years old which have carbamazepine as monotherapy in any com-mercial presentation and who are outpatients in the LICCE. Exclusioncriteria: None. Methodology: Observational descriptive.

Result: Supply problems were identified in 77% of patients, amongwhich are: Guardianship (62%), problems with a prescription (55%)claim no sickness medications (50%). Use problems as lack of adherence(61.3%), forgetfulness or difficulty in complying with times, events thatinterfere with taking the dose. 49.7% in administration consume medica-tions properly. 9% of stores or transports an inappropriate medications.Drug problems (PK / PD) in 89%, as interactions and refractory to treat-ment. As biopharmaceutical aspects related to the change of trade nameof the drug.

Conclusions: Pharmacotherapeutic monitoring to identify, prevent andresolve problems that may occur throughout the drug chain and proposeindividual solution strategies.

p675TOLERABILITY, SAFETY, AND SIDE-EFFECTS OFLEVETIRACETAM VERSUS PHENYTOIN IN INTRAVE-NOUS AND TOTAL PROPHYLACTIC REGIMENAMONGST CRANIOTOMY PATIENTS: A PROSPEC-TIVE RANDOMISED STUDYK. L. Fuller, Y. Y. Wang, M. Cook, M. A. Murphy, andW. J. D’SouzaSt Vincent's Hospital, Melbourne, Vic., Australia

Purpose: Practical choice in parenteral antiepileptic drugs (AEDs)remains limited despite formulation of newer intravenous (IV) agentsand requirements of special patient groups. We compared tolerability,safety, and side-effect profiles of levetiracetam (LEV) against phenytoin(PHT) when given intravenously and in total regimen for seizure prophy-laxis in a neurosurgical setting.

Method: This prospective, randomised, single-centre study with appro-priate blinding comprised evaluation pertaining to IV use three days fol-lowing craniotomy and at discharge, and to total IV-plus-oral regimen at90 days. Endpoints were discontinuation because of side-effect, firstside-effect, and major side-effect or seizure. Seizure occurrence and side-effect profiles were also compared.

Result: Of 81 patients randomised, 74 (36 LEV, 38 PHT) received par-enteral AED. No significant difference attributable to IV use was foundbetween LEV and PHT in discontinuation because of side-effect (LEV 1/36, PHT 2/38, p=1.00) or number of patients with side-effect (LEV 1/36,PHT 4/38, p= 0.36). No significant difference was found between LEVand PHT total IV-plus-oral regimen in discontinuation because of side-effect (hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.21 to 2.92,

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p=0.72) or number of patients with side-effect (HR 1.51, 95% CI 0.77 to2.98, p=0.22). More patients assigned PHT suffered an undesirable out-come for safety of major side-effect or seizure (HR 0.09, 95% CI 0.01 to0.70, p=0.002). Seizures occurred only amongst patients assigned PHT(n=6, p=0.01).

Conclusion: LEV and PHT were well-tolerated perioperatively paren-terally, and in total prophylactic regimen. Comparative safety and differ-ing side-effect profile of IV LEV supports use as an alternative to IVPHT.

p676THE EFFECTS OF ESLICARBAZEPINE, R-LICA-RBAZEPINE, OXCARBAZEPINE AND CARBAMAZE-PINE ON SODIUM CURRENTS THROUGH NAV1.3CHANNELSL. Wright*, K. Brady�, S. Hebeisen�, and P. Soares-Da-Silva�

*BIAL – Portela & Ca. SA, S¼o Mamede do Coronado,Portugal; �B’SYS GmbH, Witterswil, Switzerland; and�University of Porto, Porto, Portugal

Purpose: Eslicarbazepine acetate (ESL) is approved in Europe asadjunctive therapy for partial-onset seizures in adults. ESL undergoesrapid and extensive first pass metabolism via hydrolysis to eslicarbaze-pine, its major active metabolite. This study was aimed to determine theeffects of eslicarbazepine, R-licarbazepine (minor metabolite of ESL),oxcarbazepine (OXC) and carbamazepine (CBZ) on the human NaV1.3sodium channel expressed in CHO cells.

Method: About 24–48 hours following transfection with humanNaV1.3 cDNA, cells were ready for electrophysiological experiments.The whole-cell patch-clamp technique was used to investigate theeffects of eslicarbazepine, R-licarbazepine, OXC and CBZ on NaV1.3inward peak currents. These compounds were tested at various hold-ing potentials (-80 mV and -60 mV). The affinities of the test com-pounds (250 lM) for the resting (KR) and inactivated (KI) states wereexamined after 15 s conditioning pre-pulses ranging from -120 mV to-40 mV.

Result: The potency of inhibition was highly sensitive to the holdingpotential, increasing with depolarisation, but the affinity of eslicarbaze-pine was approximately 3-fold lower than CBZ and OXC in more depo-larized conditions. All compounds demonstrated a much higher affinityfor the inactivated (KI) state of the channel, but the affinity of es-licarbazepine and R-licarbazepine for VGSCs in the resting (KR) statewas about 2-fold lower than that of CBZ and OXC.

Conclusion: Eslicarbazepine demonstrated a greater selectivity for theinactive state of NaV1.3 sodium channels, which is the common featureof the rapidly firing neurons, over their resting state as compared to CBZand OXC.

p677FIRST EXPERIENCE WITH RETIGABINE IN A HIGHLYDRUG RESISTANT POPULATION OF 29 EPILEPTICPATIENTSC. Kurth, and B. J. SteinhoffEpilepsy Centre Kork, Kork, Germany

Purpose: Retigabine is available in Germany since May 2011. Thisstudy reflects the practical experiences in a tertiary referral Epilepsy-Centre.

Method: 29 consecutive patients were followed. Exclusion criteria: pro-gressive disease, psychogenic seizures, participation in another treatmentstudy, epilepsy surgery or VNS implantation during retigabine treatment.Demographic data, aetiology of epilepsy, treatment response, co-medica-tion and side effects were recorded.

Result: 29 patients (19 men, median age 36 (22–72)) were included.Median seizure rate before retigabine treatment: 20/month (2–80), med-ian number of antiepileptic drugs over lifetime: 12 (4–23), median dura-tion of epilepsy: 27 years (10–65). Titration: according to productinformation, initially up to 600mg/day. Median dosage: 600mg/day(200mg–1200mg). Main aetiologies: 44.8% cryptogenic, 13.9% FCD,10.5% complex cerebral malformation. Unsuccessful epilepsy surgery orVNS-implantation in 34.5% before retigabine treatment. Main co-medi-cations: 41.1% oxcarbazepine, 37.9% levetiracetam, 34.5% lacosamide.Median number off AEDs in co-medication: 2 (1–4). Responder rates:0% seizure-free, 6.8% seizure reduction (SR) 75–99%, 10.5% SR 50–74% (=17.3% responder), 79.3% SR below 50%, 3.4% worsening. Sideeffects: Seen in 44.8% of the patients. Main adverse reactions: 20.6% diz-ziness, 20.6% tiredness, 10.3% diplopia. Medication was tapered in65.9% of the patients (31.1% lack of effect, 17.2% side effects, 17.2%lack of effect and side effects).

Conclusion: Compared to the pivotal trials responder rates in ourpatients were lower: 17.3% versus 28–56% (depending on dosage). Thismay be due to our highly therapy-resistant population. Main side effectsand tapering rate of retigabine due to side effects in our patients were sim-ilar to those described in the other trials.

p678THE EFFECTS OF MORPHINE AND NALOXON ONSPONTANEUSE SEIZURE ACTIVITY IN HIPPOCAM-OPAL SLICESA. Alijarahi, and M. AminiQazvin, Iran

Purpose: There is however very little information available about theeffects of morphine on recurrent spontaneous seizures.

Objective: Therefore the present study was designed to determine theeffects of different dose of morphine and Naloxon on spontaneous seizureactivity in epileptogenic hippocampal slices.

Method: Hippocampal slices (~400 lm) were prepared from young Wi-star rats (P15- 25). Seizure activity was induced by continuously perfus-ing the slices with low Mg2+ perfusate in an interface recordingchamber. Extracellular recordings were performed in the hippocampalCA1 pyramidal cell layer. Low Mg2+ caused spontaneous epilepticactivity in all studied hippocampal slices. Seizure activity was quantifiedby measuring the amplitude and duration of the ictal events as well astheir number before and after the application of the study drugs. Also, thenumbers of interictal spikes were determined to complement the analysisof seizure discharges before and after drug application.

Result: Findings: Low doses of morphine (10 lM) suppressed seizureactivity, whereas high doses of morphine (15, 30 & 100 lM) potentiatedseizure activity in a dose dependent manner. This effect was completelyreversed by the addition of Naloxon (10 �M). Differential effects of mor-phine on seizures, suggests that morphine in different concentrations actson different receptor subtypes or by different mechanisms.

Activation of opioid receptors by morphine lead to suppression ofGABAergic synaptic transmission thereby disinhibiting pyramidal neu-rons, resulting in the enhancement seizures.

Conclusion: Activation of opioid receptors by morphine lead to sup-pression of GABAergic synaptic transmission thereby disinhibiting pyra-midal neurons, resulting in the enhancement seizures.

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Neuroimaging and Neurophysiology 7Wednesday, 03 October 2012

p679THE UTILITY OF HIGH FREQUENCY OSCILLATIONSON MEG AND INTRACRANIAL EEG IN LOCALISINGSEIZURE FOCI IN PATIENTS WITH REFRACTORYEPILEPSY UNDERGOING PRESURGICAL EVALUA-TIONA. Lemesiou*, M. C. Walker*, R. Rodionov*, B. Diehl�, andF. Rugg-Gunn**UCL Institute of Neurology, London, UK; and �NationalHospital for Neurology and Neurosurgery, London, UK

Purpose: With 30% of epilepsy patients not having spikes on MEG,alternative markers of epileptogenicity are sought. High frequency oscil-lations (HFOs) have been documented in patients with simultaneousMEG and intracranial EEG (iEEG) recordings and co-localisation con-firmed. We compared the ability of iEEG and MEG to identify alternativemarkers of epileptogenicity in surgical candidates.

Method: This was a retrospective analysis of MEG and iEEG data from15 pre-surgical patients. A ten minute period of slow-wave sleep wasselected for iEEG analysis. This was processed for visual detection ofHFOs which were also confirmed using newly-developed EEG algo-rithms and marked on topographic maps. Additionally, ten minutes ofcontinuous interictal resting state MEG were reviewed with a high passfilter set at 40Hz. The presence of any high frequency activity was visu-ally identified and localised using the patient's own segmented cortex assource space; source analysis using s-LORETA current density recon-struction (CURRY-5).

Result: Analysis of the 15 patients revealed only 1 without interictalMEG spikes. Analysis of HFOs in this patient revealed that channels withthe greatest number of HFOs on iEEG were found to co-localise with theseizure onset zone in the left frontal region. Despite absence of standardinterictal epileptiform discharges on MEG, we identified high frequencyoscillatory activity around 120Hz which localised to the left frontotem-poral region, consistent with other localising data.

Conclusion: The identification of high frequency oscillatory activity inMEG may be a marker of epileptogenicity contributing to non-invasivelobar localisation in patients without traditional interictal epileptiformdischarges on MEG.

p680STRUCTURAL AND FUNCTIONAL CHANGES INTHALAMO-CORTICAL CONNECTIVITY REFLECT ASPECIFIC IMPAIRED NETWORK IN JUVENILE MYO-CLONIC EPILEPSYJ. O’Muircheartaigh*, C. Vollmar�, G. J. Barker�, V. Kumari�,M. Symms§, P. J. Thompson§, J. Duncan§, M. Koepp§, andM. P. Richardson�

*Brown University, Providence, RI, USA; �University ofMunich, Munich, Germany; �King's College London, London,UK; and §UCL, London, UK

Purpose: Juvenile Myoclonic Epilepsy (JME) is the most common sub-type of idiopathic generalised epilepsy (IGE) with a presumed thalamocor-tical basis in seizure pathology. Here we investigate alterations in thalamicstructure and thalamo-cortical connectivity in Juvenile Myoclonic Epi-lepsy (JME) using multimodal magnetic resonance imaging (MRI).

Method: A cohort of patients with JME (28, mean age 33.6yrs) andhealthy control participants (38, mean age 31.8yrs) underwent a series ofstructural, diffusion and resting-state functional MRI scans. Investiga-tions focused on thalamic shape, structural connectivity of thalamocorti-

cal pathways and functional connectivity of the thalamus with corticalnetworks.

Result: Our findings demonstrated bilateral atrophy in the dorsal ante-rior and ventral posterior thalamus in the JME group. Analysis of diffu-sion tractography-derived structural connectivity showed a reduction inconnectivity from the anterior thalamus to the supplementary motor area(SMA) and preSMA. The degree of structural connectivity was positivelycorrelated with the duration of epilepsy. Finally, reduced thalamic func-tional connectivity (defined using fMRI) was detected between the sameanterior thalamic region and a cortical mesial frontal resting state net-work. The significance of all findings are corrected for multiple compari-sons (p<0.05).

Conclusion: These multi-modal and complementary results suggestdysfunction of the anterior thalamo-cortical network in JME, in keepingwith the thalamo-cortical hypothesis of IGE and frontal abnormalitiesimplicated in JME.

p681THE LOCATION OF FAST RIPPLES IS STATIONARYAS FOCAL SEIZURES EVOLVET. Nowacki, D. Gross, B. Wheatley, S. N. Ahmed, and J. JirschUniversity of Alberta, Edmonton, AB, Canada

Purpose: High Frequency Oscillations (80–600Hz) can be recordedfrom intracranial EEG (iEEG). Discrete, localized 250–600Hz ‘‘Fast Rip-ples’’ (FRs) have mainly been studied in the interictal iEEG and mayreflect epileptogenic tissue. We investigate the spatial distribution of FRsduring the evolution of epileptic seizures with respect to the convention-ally-defined seizure-onset zone (SOZ).

Method: Eighteen focal seizures from six consecutive patients undergo-ing iEEG sampled at 2000 Hz were selected. Channels were classified onconventional review of seizures as SOZ, secondary propagation, or unin-volved. Sampled 10 second sections from pre-ictal, ictal onset and propa-gation periods were visually analyzed using filters and with increasedgain for the presence of FRs.

Result: 1,955 FR events were identified. FRs increased in number withseizure evolution (median counts: 19, 55, 96.5 at the three time periods,p=0.023, Kruskal-Wallis test). During the pre-ictal period there was nosignificant difference in FR activity between groups (1-way ANOVA,p=0.359). At ictal onset, mean FR activity in the SOZ channels was sig-nificantly greater than both non-SOZ groups (1-way ANOVA, p=0.010),and the difference increased at full propagation (1-way ANOVA, p -0.001). Channels containing the greatest number of FRs (2 SD mean) laywithin the SOZ in 5/6 patients.

Conclusion: FRs predominate during electrographic seizure activity ascompared to the inter-ictal time period. They most often remain confinedto a few channels in close proximity within the conventionally-definedseizure-onset zone during the evolution of seizures. We speculate that thelocations of FRs in focal seizures may specify epileptogenic areas moreprecisely than conventional review.

p682INFERRING PATIENT-SPECIFIC PHYSIOLOGICALPARAMETERS FROM INTRACRANIAL EEG: APPLI-CATION TO CLINICAL DATAS. Shmuely*, D. R. Freestone�, D. B. Grayden*, D. Nesic*, andM. Cook**NeuroEngineering Laboratory, Melbourne, Vic., Australia;and �St. Vincent's Hospital, Melbourne, Vic., Australia

Purpose: Intracranial EEG (iEEG) provides information regardingwhere and when seizures occur, whilst the underlying mechanisms arehidden. However physiologically plausible mechanisms for seizure gen-

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eration and termination are explained by neural mass models, whichdescribe the macroscopic neural dynamics. Fusion of models withpatient-specific data allows estimation and tracking of the normally hid-den physiological parameters. By monitoring changes in physiology, anew understanding of seizures can be achieved. This work addressesmodel-data fusion for iEEG for application in a clinical setting.

Method: Data was recorded from three patients undergoing evaluationfor epilepsy-related surgery at St. Vincent's Hospital, Melbourne. Usingthis data, we created patient-specific neural mass mathematical modelsbased on the formulation of Jansen and Rit (1995). The parameters thatwere estimated include the synaptic gains, time constants, and the firingthreshold. The estimation algorithm utilized the Unscented Kalman Filter(Julier and Uhlmann, 1997).

Result: We demonstrate how parameters changed in relation to seizureinitiation, evolution and termination. We also show within-patient(across different seizures) and between-patient specificity of the parame-ter estimates.

Conclusion: The fusion of clinical data and mathematical models can beused to infer valuable information about the underlying mechanisms ofepileptic seizure generation. This information could be used to developnovel therapeutic strategies

p683THE EVENT RELATED POTENTIAL P300 AND REAC-TION TIME IN EPILEPSYV. P. Ivetic*, M. F. Knezevic-Pogancev�, and N. Naumovic**Medical Faculty, Novi Sad, Serbia; and �Institute for child andyouth health care of Vojvodina, Novi Sad, Serbia

Purpose: The research goal was the determination of amplitude andlatency value of the event related potential P300 and the determination ofthe simple reaction time, in right-handed female persons with idiopathicgeneralized epilepsy and in healthy volunteers.

Method: 50 female persons aged 19 to 23 years participated in the study.30 patients with idiopathic generalized epilepsy (first group) were com-pared with 20 healthy persons (control). The reserch workers were usingthe "oddball’’ paradigm with two tones: ‘‘standard’’ (90dB, 1000Hz) and"expected-target’’ (90dB, 2000Hz) for the registration of the P300 poten-tial above Fz and Cz (10/20 system). The subjects got instructions to pressa button, as fast as they can, whenever they hear the ‘‘expected’’ tone.

Result: The average latency values of P300 event related potential were342.2ms€11.41 above Fz and 352.1ms€5.79 above Cz area in the firstgroup; and 313.9€7.3ms above Fz; 319.1ms€12.5 above Cz in the con-trol. The amplitudes were 11.8lV€6.74 above Fz and 13.7lV€1.24above Cz in the first group; and 12.64lV€1.22 above Fz and14.26lV€1.35 above Cz in the control group. P300 latency in first groupwas significantly longer. Epileptic persons were decreased P300 ampli-tude but not significantly as compared with healthy persons. There wasno relation between P300 latency and amplitude with seizure onset, dura-tion frequency. Significantly faster RT was found in healthy persons. Inpatients with epilepsy were found a significant positive correlationbetween RT duration and latency of P300

Conclusion: The epilepsy has impact on late components of P300 poten-tial and reaction time.

p684ELECTROPHYSIOLOGICAL FEATURES IN PROGRES-SIVE MYOCLONIC EPILEPSYZ. Matur*, O. E. Ore�, N. Bebek*, B. Baykan*, C. Gurses*,A. Gokyıgıt*, and A. E. Oge**Istanbul Universty Istanbul Medical Faculty, Istanbul, Turkey;and �Ozel Memorial Hizmet Hospital, Istanbul, Turkey

Purpose: Progressive myoclonic epilepsy (PME) is a heterogeneoussyndrome of rare disorders presenting with similar clinical features. Thisstudy was designed to investigate if there was, 1) any correlation betweenthe electrophysiological findings and the clinical course of this syn-drome, 2) any change in the excitability of brainstem pathways besidesthe well-known cortical hyperexcitability.

Method: Sixteen PME patients, whose clinical and genetic features willbe presented separately, were included. Control groups consisted of 15healthy controls (HC) and 7 patients taking multiple antiepileptic drugs(patient controls=PC). Median somatosensory evoked potentials (SEP),C reflexes from thenar eminences and blink reflexes (BR) to supraorbitalstimulation were studied.

Result: Cortical N20 potential latencies were delayed and N20-P25,P25-N35 amplitudes were increased in PME group (p<0.05). Giant SEPswere recorded bilaterally in 8 PME cases whose disease duration wasfound to be longer than the other patients (p=0.045). C reflex wasrecorded in 9 cases, 6 of whom also had giant SEPs. Higher stimulusintensities were required in PME group for eliciting the BRs. The laten-cies of ipsilateral R2 responses (iR2) were prolonged in PC and PMEgroups, which were more pronounced in the former (p<0.05). The ampli-tude, duration and areas of iR2s were generally decreased in PC andincreased in PME group (p<0.05).

Conclusion: The electrophysiological markers of cortical hyperexcit-ability, giant SEPs and C reflexes, may have a relation with the courseand duration of the disease. BR findings obtained in this study imply thepresence of an increased excitability at the brainstem level.

p685NEUROPROTECTIVE POTENTIAL OF STIRIPENTOLAGAINST OXYGEN AND GLUCOSE DEPRIVATION ORGLUTAMATE EXPOSURE IN CULTURED RAT CORTI-CAL NEURONSV. Riban*, M. Verleye*, N. Callizot�, and R. Steinschneider�

*BIOCODEX, Compiegne, France; and �Neuron Expert,Marseille, France

Purpose: Experimental and clinical data indicate that epilepsy and sei-zures lead to neuronal cell loss and irreversible brain damage underlyingbehavioural and cognitive problems particurlarly in Children. Stiripentol(Diacomit(c)) is an antiepileptic compound prescribed in chilhood epilep-sies such as Dravet syndrome. We examined the potential neuroprotec-tive activity of stiripentol in two in vitro models mimicking neuronaldeath: neuronal cultures from mature rat cerebral cortex exposed toanoxia and glucose deprivation or glutamate injury.

Method: Anoxia (95%N2/5% CO2) for 2 hours followed by-re-oxygena-tion for 24 hours and glutamate (40lM for 20min) induced neuronal tox-icity. Quantification of neuronal death was based on the immunolabelingintensity of cytoskeleton components: the 68/200 KDa neurofilament su-bunits.

Result: Stiripentol up to 100lM was devoid of any effects on the neuro-filaments immunolabeling density in normoxic and control conditions.Anoxia and glutamate induced a decrease in neuronal labelling of 60 and40% respectively. At therapeutically relevant concentrations (30 and100lM), stiripentol reversed the anoxia-induced-effects in neuronallabelling in the case of pre-treatment but was ineffective when post-trea-ted. Stiripentol at 100lM included in the culture medium before or afterglutamate exposure significantly increased the amount of surviving neu-rons compared to controls.

Conclusion: Stiripentol exhibited neuroprotective properties. Severalhypotheses, such as interactions between stiripentol and the glutamater-gic system and/or with membrane calcium channels can be suggested toexplain these effects.

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p686VISUAL CORTEX HYPEREXCITABILITY IN IDIO-PATHIC GENERALIZED EPILEPSIES WITH PHOTO-SENSITIVITY: A TMS STUDYF. Brigo*, L. G. Bongiovanni�, R. Nardone�, A. Fiaschi*, andP. Manganotti§

*University of Verona, Verona, Italy; �Verona, Italy; �FranzTappeiner Hospital, Merano, Italy; and §University of Verona,Verona, Italy

Purpose: To investigate the cortical excitability levels in 33 patientswith IGEs, and in a subgroup of 8 patients affected by idiopathic general-ized epilepsies with photosensitivity, compared with 12 healthy controls.

Method: Using transcranial magnetic stimulation we explored the excit-ability of both the primary motor cortex and the primary visual cortexdetermining the resting motor threshold (rMT) and the phosphene thresh-old (PT).

Result: An inversion of the PT/rMT ratio (PT/rMT ratio <1) was foundin 87.5% epileptic patients with photosensitivity. All patients with activeepilepsy and photosensitivity showed this inversion. The differences inthe PT/rMT ratio of epilepsy patients with photosensitivity and those ofhealthy controls (p=0.007) and with epilepsy patients without photosensi-tivity (p=0.016) were statistically significant. 91.7% of the controlsreported phosphenes, compared with 45.5% of patients with idiopathicgeneralized epilepsy (p=0.015). Phosphenes were reported more fre-quently among epilepsy patients with photosensitivity (87.5%) than inpatients with active epilepsy without photosensitivity (30.8%) (p=0.038)and with patients with epilepsy in remission without photosensitivity(33.3%) (p=0.054). No differences were found between epilepsy patientswith photosensitivity and controls (p=0.648).

Conclusion: The marked decrease in PT and the high phospheneprevalence in epilepsy patients with photosensitivity indicate a regio-nal hyperexcitability of the primary visual cortex. Results of our studyargue therefore against the presence of homogeneously distributedhyperexcitability in idiopathic generalized epilepsies associated withphotosensitivity. The inversion of the PT/rMT ratio might represent auseful biomarker of this abnormal response of the human brain tovisual stimulation.

p687STABILITY OF SYNCHRONIZATION CLUSTERS ANDICTOGENICITY IN TEMPORAL LOBE EPILEPSYG. Ortega*, A. Palmigiano�, R. Garc�a De Sola*, and J. Pastor**Hospital Universitario de la Princesa, Madrid, Spain; and �

University of Buenos Aires, Buenos Aires, Argentina

Purpose: Identification of critical areas in presurgical evaluations ofpatients with temporal lobe epilepsy is the most important step prior toresection. According to the ‘‘epileptic focus model’’, localization of sei-zure onset zones is the main task to be accomplished. Nevertheless, a sig-nificant minority of epileptic patients continue to experience seizuresafter surgery (even when the focus is correctly located), an observationthat is difficult to explain under this approach. However, if attention isshifted from a specific cortical location toward the network propertiesthemselves, then the epileptic network model does allow us to explainunsuccessful surgical outcomes.

Method: The intraoperative electrocorticography records of 20 patientswith temporal lobe epilepsy were analyzed in search of interictal syn-chronization clusters. Synchronization was analyzed, and the stability ofhighly synchronized areas was quantified. Surrogate data were con-structed and used to statistically validate the results.

Result: Our results show the existence of highly localized and stablesynchronization areas in both the lateral and the mesial areas of the tem-poral lobe ipsilateral to the clinical seizures. Synchronization areas seemto play a central role in the capacity of the epileptic network to generateclinical seizures. Resection of stable synchronization areas is associatedwith elimination of seizures; nonresection of synchronization clusters isassociated with the persistence of seizures after surgery.

Conclusion: We suggest that synchronization clusters and their stabilityplay a central role in the epileptic network, favoring seizure onset andpropagation. We further speculate that the stability distribution of thesesynchronization areas would differentiate normal from pathologic cases.


p688HIGHLY FOCAL BOLD ACTIVATION ON FMRI INPATIENTS WITH PROGRESSIVE MYOCLONIC EPI-LEPSY AND DIFFUSE GIANT SOMATOSENSORYEVOKED POTENTIALSP. Manganotti*, S. Storti*, E. Formaggio*, F. Brigo*,A. Delfelice*, I. Boscolo Galazzo*, L. Canafoglia�, and L.G. Bongiovanni**Universit degli Studi di Verona, Verona, Italy; and �IRCCSFoundation Besta Neurological Institute, Milan, Italy

Purpose: Aim of the study was to analyzed the effect of afferent inputon patterns of brain electrical activation in eour patients with progressivemyoclonic epilepsy (PME) by measuring the somatosensory evokedpotential (SSEP) amplitude at the scalp after median-nerve stimulationand examining the changes in the functional magnetic resonance imagingblood oxygen level-dependent (fMRI BOLD) signal.

Method: To locate the right median nerve at the wrist, the stimulationintensity and electrode sites were altered until stimulation produced anobservable thumb twitch. Current stimulation during fMRI recordingwas done in an alternating sequence of 26 seconds. Coregistration System(Micromed) was used.

Result: High amplitude SSEPs diffused over the scalp with high ampli-tude N20 and P25 were oberved in all the patients, but it was associatedwith highly focal BOLD activation of the contralateral sensorimotorareas. By contrast, no diffuse activation of either the frontal or the poster-ior parietal cortical areas was observed, as seen with previously recordeddata of SSEPs from a healthy control group.

Conclusion: The highly focal BOLD activation in these patients sug-gests that cortex hyperexcitability might be limited to the sensorimotorcortex in PME. The combined EEG-fMRI findings highlight a dissocia-tion between BOLD activation and neurophysiological findings.

p689INTRACRANIAL EEG-FMRI IN EPILEPSY: A PRELI-MINARY APPROACH TO MODELING VERY FRE-QUENT SPIKE DISCHARGESD. W. Carmichael*, L. Hu�, U. Chaudhary�, G. Iannetti§,S. Vulliemoz–, R. Rodionov�, R. Thornton�, and L. Lemieux�

*UCL Institute of Child Health, London, UK; �SouthwestUniversity, Chongqing, China; �UCL Institute of Neurology,London, UK; §UCL, London, UK; and –University Hospital ofGeneva, Geneva, Switzerland

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Purpose: We have recently recorded intracranial electroencephalogra-phy (icEEG) in epilepsy patients undergoing presurgical evaluation withsimultaneous fMRI observing a strict protocol to ensure minimal risk ofpatient injury. Many epileptifom interictal discharges (IEDs) arerecorded (often<1 per second). When IEDs are very frequent they arepoorly modeled by uniform instantaneous events. We investigate if mod-elling IED amplitude and morphology increased sensitivity to IEDrelated BOLD changes using a new method.

Method: Three temporal lobe epilepsy patients undergoing presurgicalevaluation with icEEG and were scanned within strict safety criteria.

IEDs were visually coded; the most frequent spike type was selectedfrom the most prominent spiking contact. A model containing amplitude,latency and dispersion terms for each IED phase (e.g. spike and wave)was fitted to each of these IED. The resulting coefficients were entered asIED features along with onsets as regressors in a model of fMRI signalchanges.

The variance explained by IED onsets and features was obtained usingan inclusive threshold (p<0.001 uncorrected, >5 adjacent voxels) in eachpatient.

Result: Patient#1: IED onset revealed diffuse responses with a smallcluster in the temporal lobe. IED features explained additional vari-ance in one left-mid-posterior temporal cluster.

Patient#2: IED onset showed no result. IED features showed a leftparietal and right-basal-temporal changes. Interestingly, the dispersioncoefficients revealed clusters within the right and left temporal lobeswhich both lay within the IZ.

Patient#3: IED onset showed distributed clusters predominantly con-tralateral to the IZ. IED features revealed an additional right-mid-poster-ior temporal cluster ipsilateral to the IZ.

p690VOLUMES OF SUBCORTICAL STRUCTURES IN IDIO-PATHIC GENERALISED EPILEPSY AND UNAFFECTEDFAMILY MEMBERSF. A. Chowdhury, G. J. Barker, L. Nashef, R. D. Elwes, andM. P. RichardsonKing's College Hospital, London, UK

Purpose: Reduced volumes of thalamus and caudate have been reportedin patients with idiopathic generalised epilepsy (IGE). It is uncertainwhether this is part of the underlying disease process, or a consequenceof seizures or drug treatment.

Method: Forty normal control subjects, 30 patients with IGE, and 36unaffected first-degree relatives of the patients were studied. A T1-weighted SPGR image was acquired at 3T for each subject, with isotropicvoxels of 1.1mm. Each scan was processed using the software packageFSL-FIRST (FMRIB, Oxford). Volumes of thalamus, caudate, putamenand pallidum were obtained for left and right hemispheres (8 volumes foreach subject). Statistical testing used Bonferroni correction for 8 compar-isons.

Result: Patients had lower volumes of thalamus, caudate, putamen andglobus pallidus bilaterally than relatives, who in turn had lower volumesof these regions than controls. For right thalamus and right caudate thesewere significant, with patients and relatives showing significantly lowervolumes than controls (right thalamus. F=5.51, p=0.005; post hocpatients versus controls p=0.032, relatives versus controls p=0.002; rightcaudate F=4.95, p=0.006; post hoc patients versus controls p=0.006, rela-tives versus controls p=0.014). In all other regions, there were strongtrends but these were not statistically significant after correcting for mul-tiple comparisons.

Conclusion: Volume reduction of subcortical structures is found inunaffected relatives of patients with IGE as well as the patients them-selves, suggesting this is not related to the occurrence of seizures or dueto treatment.

p691INFERRING PATIENT-SPECIFIC PHYSIOLOGICALPARAMETERS FROM INTRACRANIAL EEG: THEO-RETICAL STUDIESD. R. Freestone*, D. B. Grayden*, M. Cook*, and D. Nesic�

*University of Melbourne, Parkville, Vic., Australia; and�NeuroEngineering Laboratory, Melbourne, Vic., Australia

Purpose: Mathematical neural mass models describe the biophysics ofthe EEG. These models are used in epilepsy research to generate newhypotheses for changes in physiology that lead to generation of seizures.Until now, these models have had limited use in the clinic since theydescribe general neurodynamics, while pathologies are patient-specific.This work describes theoretical aspects of a method for creating patient-specific neural mass models from intracranial EEG (iEEG).

Method: Artificial data were generated using a neural mass mathemati-cal model (Jansen and Rit, 1995) so that the actual parameters wereknown and estimation accuracy could be evaluated. The dynamics of themodel that were estimated were firing rates and membrane voltages. Theestimated parameters governed the shape of post-synaptic potentials,connectivity strength between neural populations, and firing thresholds.An augmented state-space model was used with the Unscented KalmanFilter (Julier and Uhlmann, 1995) to solve the estimation problem.

Result: Use of the artificial data demonstrated that it is possible to esti-mate the dynamics and parameters of the model from iEEG. Estimationaccuracy and robustness were also demonstrated.

Conclusion: The data assimilation framework allows observation ofphysiological parameters that govern neurodynamics. Patient-specificmodels have the potential to lead to tailored drugs delivery and facilitateengineering techniques for feedback control of seizures. B.H. Jansen andV.G. Rit. Electroencephalogram and visual evoked potential generation ina mathematical model of coupled cortical columns, Biological Cybernet-ics (1995), 73(4) 357–366 S.J. Julier and J.K. Uhlmann. A new extensionof the Kalman filter to nonlinear systems, SPIE 3068 (1997), 182–193.

p692EFFECTS OF VAGAL NERVE STIMULATION ONVOCAL FUNCTIONSE. Gardella*, P. Schiavo�, A. Maccari�, E. Zambrelli�,C. Marras�, G. Felisati�, and M. P. Canevini�

*Filadelfia Epilepsihospitalet, Dianalund, Denmark; �St PaoloHospital, Milan, Italy; and �IRCCS Neurological Institute CarloBesta, Milano, Italy

Purpose: This study aims to describe the subjective and objectiveeffects of Vagal Nerve Stimulation (VNS) on vocal functions

Method: We studied 14 patients (7 males/ 7 females) affectred by drugresistant epilepsythat underwent VNS implantation. Mean patients age-was 41 years. Latency from implantation ranged from 1 to 8 years.Patients subjecticve disturbs have been investigated performing anunstructured colloquium and by self administered questioner. Vocalfunctions have been studied by means of larygeal fibroscopy (LF) andvocal analysis (MultiDimensionalVoiceProgram Kay Pentax TM) both atrest and dring VNS stimulation.

Result: (a) immediatly after implantation patients (n�4) referredchronic dysphonia +/) dysphagia, that could periodically and intermit-tently worsen, in relation to VNS discharge. Chronic disturbs graduallyrecovered 2–3 months after surgery, whilst in most cases intermittentdysphonia was also present for 3–10 days after each following incre-ment of the VNS amperage. LF and VA documented unilateral hypo-mobility of vocal cord and phonological alteration while the stimulatorwas switched off; disturbs worsened during VNS discharges. (b)

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patients studied (n�10) after 1–8 years from implantation, occasionallyreferred vocal disturbs (2 patients presented sporadically intermittentdysphonia). LF and VA documented in 9/10 cases a residual hypomo-bility of the vocal cord, functionally compensated from the contralat-eral vocal cord hyperadduction.

Conclusion: We documented that both surgergical procedure and elec-trical stimulation of the vagal nerve can perturb the motility of the vocalcord homolateral t the side of implantation. This incostantly producesnegative effects on vocal productions and occasionally is referred bypatients as a chronic disturb.

p693LOCALISING AND LATERALISING VALUE OF ICTALEEG PATTERNS IN MESIAL AND NEOCORTICALTEMPORAL LOBE EPILEPSYE. T. Lim*, S. Kovac�, T. Wehner�, C. Scott�, and B. Diehl§

*Instituta of Neurology, London, UK; �Department of Clinicaland Experimental Epilepsy, London, UK; �The NationalHospital for Neurology and Neurosurgery, London, UK; and§UCL Institute of Neurology, London, UK

Purpose: To study the localizing and lateralizing value of ictal scalpEEG patterns in patients with mesial and neocortical temporal lobe epi-lepsy (TLE).

Method: Eighty-five EEG seizures in 39 patients with TLE were analy-sed. The first 20 seconds of seizure patterns were classified as rhythmic(alpha, theta, delta), repetitive epileptiform or arrhythmic. Their distribu-tion was classified as regional, lateralized, lateralized-maximum tempo-ral, generalised, generalised- bi-temporal emphasis, or bi-hemisphericindependent. The location of the epileptogenic zone was determined byseizure freedom after lesionectomy or temporal lobectomy with histolog-ically confirmed hippocampal sclerosis (n=25) or intracranial EEGrecording (n=14).

Result: Sixteen patients had neocortical TLE (intracranial EEG record-ing n=9 and temporal lesionectomy n=7) and 23 mesial TLE (intracranialEEG recording n=5, temporal lesionectomy n=2 and anterior temporallobectomy n=16).

Patients with mesial TLE were more likely to have rhythmic or repeti-tive epileptiform ictal patterns (54% in mesial TLE versus 23% in neo-cortical TLE), whereas patients with neocortical TLE were more likely tohave arrhythmic ictal patterns (17% neocortical TLE versus 6% mesialTLE) (p=0.04, Fisher's exact test). There was no difference in ictal onsetfrequencies. In mesial TLE, 58% of seizures localized, 37% lateralized(including temporal maxima) and 5% bi-hemispheric independent. Inneocortical TLE, 40% of seizures localized, 33% lateralized and 7% bi-hemispheric independent. Generalised ictal onset was present in 20% ofneocortical TLE, but never seen in mesial TLE (p=0.15, Fisher's exacttest).

Conclusion: Arrhythmic ictal patterns and possibly a generalised distri-bution should raise suspicion of neocortical ictal onset in TLE.

p694VIDEO-ELECTROENCEPHALOGRAM MONITORINGIN A PEDIATRIC EPILEPSY UNITP. Giner-Bayarri, N. Torres, K. Quintero-Hernandez,J. Moliner-IbaÇez, M. R. Chilet-Chilet, A. C�novas, G. Zalve-Plaza, R. Bret�n, and L. Ruiz-MarquezHospital Universitario Dr. Peset, Valencia, Spain

Purpose: The characteristics of epilepsy in childhood and the differ-ences that show with adult population, make it increasingly necessary, tocreate specific units for diagnosis and treatment of epilepsy in pediatricpatients. To assess the effectiveness of the videoelectroencephalogram(vEEG) in epileptic children.

Method: A total number of 20 patients with suspicion of epilepsy,between 24 months and 16 years old, have been studied during theyear 2011–2012 with videoEEG monitoring from 24 to 96 hours. Tol-erability to the exploration is valued, the required time to register a sei-zure, the number of the recorded seizures and the efficiency in eachpatient.

Result: Al the patients tolerated the realisation of the exploration. In 19of the 20 patients of the study the events that the parents referred as sei-zures were recorded, letting to approach to a definitive diagnosis of thepathology. In 6 of the 20 patients pseudoseizures were diagnosed, lettingto proceed to the stop of medication.

Conclusion: The utilisation of VEEG in pediatric epilepsy unit is notonly useful in obtaining the accurate diagnosis, but also in avoiding thetreatment in patients with uncertain symptoms.

p695EEG FINDINGS AND TREATMENT IN JUVENILE MYO-CLONIC AND JUVENILE ABSENCE EPILEPSIESS. V. Kasradze*, G. Japaridze*, D. Kvernadze*,L. Zhizhiashvili*, T. Gagoshidze*, G. Lomidze*, O. Toidze*, andJ. W. Sander�

*Institute of Neurology and Neuropsychology, Tbilisi, Georgia;and �UCL Institute of Neurology, London, UK

Purpose: Focal EEG abnormalities are often described in idiopathicgeneralized epilepsy (IGE), but there have been few investigations withrespect to EEG and AED treatment.

Aim: To assess EEG features in juvenile myoclonic epilepsy (JME) andjuvenile absence epilepsy (JAE) in relation to AED treatment.

Method: EEGs of 122 consecutive people, aged 9 to 54 years (mean€SD =25.4€10.3), admitted to the INN between 01/08 and 2/10 anddiagnosed with JME (n=95) and JAE (n=27), were analyzed. 41 ofthem were deemed as treated appropriately, [regular treatment regimeand adequate dosage of valproate (n=29), levetiracetam (n=3), lamotri-gine (n=2), phenobarbital (n=5) or polytherapy; 21 were deemed astreated inappropriately [mainly carbamazepine mono-therapy] 60 peo-ple were drug-na�ve.

Result: EEG was normal in 21/122 (17%). Of those on appropriatetreatment it was normal in 32% and this compares to 13% in drug-na�ve subject and in none of those inappropriately treated (p = 0.004).Specific Generalized epileptiform abnormalities were seen in 32% ofpeople with appropriate AED treatment, in 86% with inappropriatetreatment and in 73.3% drug-na�ve individuals. Focal epileptiformabnormalities were noted in 81% of people with inadequate treatment,in 50% of drug-na�ve (p = 0.013), in 49% of adequately treated people(p = 0.015).

Conclusion: In this Georgian sample of people with IGE, appropriateantiepileptic treatment seems more likely to be associated with the pres-ence of normal EEG patterns in people with IGE; inappropriate drug-treatment seems to have no effect on generalized discharges and seems toexarcebate focal epileptiform abnormalities.

p696TOWARDS GUIDELINES FOR THE RATIONAL USE OFTHE PROLONGED EEGF. Z. Javaid, T. Tidswell, and H. Angus-LeppanRoyal Free Hospital, London, UK

Purpose: The diagnosis of epilepsy is primarily clinical. Basic EEGinvestigations are usually requested in order to confirm or aid the

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diagnosis. When these results are normal or inconclusive, patients arefurther referred for more specialised investigations. This study aimedto compare and assess the relative uses of prolonged EEGs (ambula-tory EEG versus video telemetry) in the diagnosis and clinical manage-ment of epilepsy.

Method: 104 consecutive patients had a prolonged EEG betweenNovember 2009 and February 2011. Clinical records were assessed retro-spectively for changes in either diagnosis or clinical management.

Result: Of 81/104 patients (57 females), mean age of 38€13 yearswith sufficient data for analysis; 44% had a change in diagnosis; 26%had EEG support for non-epileptic attack disorder (NEAD); and in30% of patients, diagnosis was unchanged. Video telemetry was lesslikely to lead to a change in diagnosis than ambulatory EEG, but morelikely to provide support for a diagnosis of NEAD (p< 0.0001). 72patients had reassessment of treatment, and 47% had a change in medi-cation.

Conclusion: This study highlights the influence of the ambulatory EEGin overall patient management and medication, and the role of videotelemetry in diagnosis of NEAD. Based on this evidence we suggestguidelines on when to use ambulatory versus telemetry EEG in referredpatients.


p697INTRACRANIAL EEG SEIZURE-ONSET PATTERNS INTEMPORAL LOBE EPILEPSY AND THEIR ASSOCIA-TION WITH OUTCOME, LOCALIZATION, AND HIS-TOLOPATHOLOGYI. Dolezalova, M. Brazdil, I. Tyrlikova, M. Hermanova, I. Rektor,and R. KubaSt. Anne's University Hospital and Faculty of Medicine, MasarykUniverzity, Brno, Czech Republic

Purpose: We performed a retrospective study to determine the differenttypes of seizure onset patterns (SOP) in intracranial EEG in patients withtemporal lobe epilepsy (TLE).

Method: We analyzed a group of 51 patients (172 seizures). We ana-lyzed the SOP frequency during the first 3 seconds after the onset ofictal activity. The average frequency was measured. The cut-off valueto distinguish between fast and slow frequency was 8 Hz. Based onthese criteria, we defined three types of SOP: 1. fast ictal activity(FIA) - frequency >8 Hz; 2. slow ictal activity (SIA) - frequency <8Hz; and 3. focal attenuation (FAT) - no clean-cut activity was present.We tried to find the relationship between SOP types and outcome ofsurgery (Engel I versus Engel II-IV), histopathological findings (hippo-campal sclerosis, focal cortical dysplasia, other lesions and negativefindings) and localization of the seizure onset zone (mesial, temporo-polar, lateral).

Result: In TLE patients (N=51), significantly more patients classified asEngel I had FIA and significantly fewer patients with Engel I had SIA incomparison to patients classified as Engel II-IV (p<0.001). Significantlymore patients with focal cortical dysplasia had SIA in comparison toother histopathological findings (p=0.03). There were no statistically sig-nificant relationships between the SOP and the localization of the seizureonset zone.

Conclusion: Our study suggests that the SOP frequency at the very earlyonset of epileptic seizure in patients with TLE could be a predictive factorof the outcome.

p698EVALUATION OF THE UTILITY OF LONG TERMVIDEO-EEG MONITORINGM. Caballero, R. Vazquez, P. M. Martinez, C. Martinez-Quesada, and M. D. JimenezUniversity Hospital Virgen del Rocio, Sevilla, Spain

Purpose: Long-term Video-EEG monitoring is widely used for diagno-sis, seizure classification and presurgical evaluation of patients with epi-lepsy. We evaluate the percentage of patients admitted in our video-EEGunit for diagnosis or presurgical work-up whose preadmission diagnosisand treatment was changed after video-EEG monitoring.

Method: Data from a consecutive cohort of patients admitted over oneyear to the inpatient video-EEG unit of a tertiary hospital in Spain wasretrospectively evaluated. Diagnosis and treatment of these patientsbefore and after admission to the unit were compared.

Result: 59 inpatient video-EEG monitoring studies were done during oneyear. Seizures have been recorded in 50 patients (84%). Preadmissiondiagnosis was confirmed in 39 cases (66.1%) (Including those cases forpresurgical evaluations). Video-EEG monitoring results have changed thediagnosis of the type of seizure in 20 patients (33.9%). In addition, phar-macological treatment was changed after video-EEG in 25 patients (44%).

Conclusion: The results of this study demonstrate that long term video-EEG monitoring is needed for the proper diagnosis and accurate treat-ment in patients with seizure disorders. Further studies that evaluate thecost-benefits of long-term video EEG monitoring and accurate diagnosisand pharmacological treatment are needed.

p699APPLICATION OF DIFFUSION TENSOR IMAGING INDRUG-RESISTANT EXTRA-TEMPORAL EPILEPSYWITH FOCAL CORTICAL DYSPLASIA IN MRI: COR-RELATION WITH FDG-PET HYPOMETABOLIC AREAJ. Aparicio*, A. Donaire*, X. Setoain*, S. Rub�*, N. Bargall�*,A. Calvo�, C. Falc�n�, and M. CarreÇo**Hospital Cl�nic, Barcelona, Spain; and �IDIBAPS, Barcelona,Spain

Purpose: Approximately, 40–50% of patients with focal epilepsy aredrug-resistant and might benefit from epilepsy surgery. The detection ofa brain MRI lesion increases surgical success being close to 70%. Theaim was to study whether diffusion tensor MRI (DTI) is able to determinethe location and extent of the ‘‘lesion area’’ (LA) in patients with extra-temporal epilepsy and focal cortical dysplasia (FCD) in MRI. DTI abnor-malities were correlated with the MRI and compared with hypometabolicarea depicted by FDG-PET.

Method: We have selected 7 patients with drug-resistant extra-temporalepilepsy and visible cerebral MRI lesion (FCD). All the patients under-went a comprehensive presurgical evaluation. The control group wascomposed of 30 healthy subjects. We compared the fractional anisotropy(FA) and mean diffusivity (MD) maps for each patient with the controlgroup, ‘‘one against all’’, by using a t-test for two independent samples.

Result: It has been observed an increase in MD, mainly in the sub-corti-cal region behind the FCD, and a decrease in FA in the white matter tractspotentially involved in the spread of epileptic seizures. In addition, theincreased MD clusters were concordant with the FDG-PET hypometabo-lism.

Conclusion: In conclusion, DTI may be a non-invasive technique usefulpresurgical evaluation, because in most cases can offer complementaryinformation about the location of the LA and the main pathways involvedin seizures spread.

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p700DIAGNOSTIC ACCURACY OF [11C]-METHIONINE PETFOR THE DIFFERENTIATION BETWEEN DYSEMBRY-OPLASTIC NEUROEPITHELIAL TUMOUR ANDOTHER EPILEPTOGENIC BRAIN NEOPLASMSS. Rheims*, S. Rub�*, E. Bernard�, S. Bouvard�,N. Streichenberger�, M. Guenot*, and P. Ryvlin**Hospices Civils de Lyon, Lyon, France; �CERMEP-Imageriedu vivant, Lyon, France; and �Hpital Neurologique, Lyon,France

Purpose: Brain tumours responsible for longstanding partial epilepsyare characterised by a high prevalence of dysembryoplastic neuroepithe-lial tumour (DNT), whose natural evolution is much more benign thanthat of gliomas. Previous studies have suggested that [11C]-methioninepositron emission tomography (MET-PET) could help to distinguishDNTs from other epileptogenic brain tumours, optimising the therapeuticstrategy for this type of tumour. The current study reassessed in a largerpopulation the diagnostic accuracy of MET-PET for the differentiationbetween DNT and other epileptogenic brain neoplasms.

Method: Retrospective study of 48 patients with partial epilepsy of atleast six months duration related to a non-rapidly progressing braintumour on MRI who underwent MET-PET. A structured visual analysis,which distinguished between normal, moderately abnormal, or markedlyabnormal tumour methionine uptake, as well as various regions of inter-est and semiquantitative measurements were conducted.

Result: Pathological results showed 20 DNTs (41.7%), 10 ganglioglio-mas (20.8%), 16 low-grade gliomas (33.3%) and two high-grade gliomas(4.2%). MET-PET visual findings significantly differed between the var-ious tumour types (p<0.001), regardless of gadolinium enhancement onMRI, and were confirmed by semiquantitative analyses (p<0.001 for allcalculated ratios). All gliomas and gangliogliomas were associated withmoderately or markedly increased tumour methionine uptake, whereas 9/20 DNTs had normal methionine uptake. The only two DNT which pre-sented with a marked MET-PET abnormality showed a specific histologi-cal pattern, including a pilocytic contingent.

Conclusion: Normal MET-PET findings in patients with an epilepto-genic and non-rapidly progressing brain tumour are suggestive of DNT,whereas a markedly increased tumour methionine uptake makes thisdiagnosis unlikely.

p701FIBER DENSITY ASYMMETRY IN TEMPORAL LOBEEPILEPSYM. Okujava, F. Todua, M. Beraia, and T. AntiaResearch Institute of Clinical Medicine, Tbilisi, Georgia

Purpose: Study aimed to define most evident lateralizing signs in whitematter associated with hippocampal pathology.

Method: Diffusion tensor based tractography of the major white mattertracts passing temporal lobes were studied in 16 patients with hippocam-pal sclerosis (HS) and 15 patients with cryptogenic temporal lobe epi-lepsy. 30 healthy controls were studied to reveal the normal variations ofthe white matter side-to-side asymmetries. White matter tracts in parahip-pocampal gyrus, fornix, cingulum, inferior longitudinal fasciculus, unci-nate fasciculus, arcuate fasciculus, external capsule and temporal polewere studied. Tract density was calculated as number of fibers passingthrough the given region of interest.

Result: Side of the seizure origin in HS patients was strongly associatedwith the fiber reduction in the fornix. Less evident asymmetry wasrevealed for parahippocampal gyrus and temporal pole. In the group ofcryptogenic TLE there was a trend of decrease of parahippocampal tracts,

no other specific asymmetry was established in this group of patients.Normal controls showed slight intraindividual differences in asymmetryof various white matter tracts. Hence less than ten percent side-to-sidedifference in different white matter tracts density should be treated withcaution for the lateralization of the pathology.

Conclusion: It can be concluded that fiber reduction in the fornix is thestrongest tractographic sign of ipsilateral hippocampal sclerosis.

p702SUBTRACTION ICTAL SPECT CO-REGISTERED TOMRI (SISCOM) IN CHILDREN WITH EPILEPTICSPASMSL. Wong-Kisiel, K. Nickels, and E. WirrellMayo Clinic, Rochester, MN, USA

Purpose: Surgical intervention for epileptic spasms can be challenging,due to the lack of localizing EEG and MRI findings. The aim of this studyis to evaluate the localizing value of SISCOM in young children with epi-leptic spasms.

Method: Children with epileptic spasms who underwent SISCOMbetween January 1996 and December 2009 were identified from the Pedi-atric Epilepsy Monitoring Unit Database at Mayo Clinic Rochester. Chil-dren were defined as having lateralized spasms if semiology suggestedfocal onset. Other concurrent seizure types were recorded. Results ofMRI (focal, unilateral hemispheric, bihemispheric and nonlesional) andSISCOM evaluations (localizing, nonlocalizing) were abstracted by chartreview. Concordance between MRI and SISCOM was based on EpilepsySurgery Conference report.

Result: Thirteen children (median age 21 months; male 38%) with epi-leptic spasms were identified. All had a generalized ictal EEG correlateto their spasms. In 8 (62%), semiologic features suggesting focal onsetwere present. MRI brain abnormality was focal in 2 (15%), unilateralhemispheric in 4 (31%), nonlesional in 3 (23%) and bihemispheric in 4(31%) patients. SISCOM abnormality was localizing in 6 (46%) patients,including 4 (50%) with lateralized spasms. In those with a localizing SIS-COM, 2 had concordant focal MRI findings, 2 had an ipsilateral SISCOMfocus with a hemispheric MRI abnormality, and two patients had bihemi-spheric malformations.

Conclusion: Focal and lateralized MRI findings and lateralized clinicalfeatures are associated with focal SISCOM abnormalities. SISCOM canbe considered in evaluating young children for epilepsy spasm whenother noninvasive presurgical evaluations are unrevealing.

p703CONTRIBUTIONS OF EEG/FMRI TO LOCALIZINGFOCAL CORTICAL DYSPLASIAF. Pittau*, L. Ferri�, F. Fahoum*, F. Dubeau*, and J. Gotman**Montreal Neurological Institute and Hospital, McGillUniversity, Montreal, QC, Canada; and �IRCCS Istituto delleScienze Neurologiche, Bologna, Italy

Purpose: To examine the contribution of the BOLD response in localiz-ing the lesion in patients with focal cortical dysplasia (FCD).

Method: Patients with focal epilepsy and FCD who underwent 3T EEG/fMRI from 2006 to 2010 were included. The diagnosis of FCD was basedon neuroradiology (MRI+), or histopathology (MRI-). All underwent a120 min recording session. IEDs similar to those recorded outside thescanner were marked in the filtered EEG. The lesion (in MRI+) or theremoved cortex (in MRI-) were blindly marked on the anatomical T1sequence, after revising the FLAIR images. For each BOLD response weassessed the concordance with the spike field and the concordance with

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the lesion in MRI+ or the removed cortex in MRI-. BOLD responses wereconsidered ‘‘concordant’’ if the maximal t-value was inside or up to 1 cmaway from the marking.

Result: Twenty-one patients were included (14 MRI+, 7 MRI-). In 7patients (6 MRI+, 1 MRI-) the EEG was not active or there were artifactsduring acquisition. Eight MRI+ were analyzed. In 6/8 (75%) patients atleast one BOLD response had the max t value inside the lesion. Six MRI-were analyzed: in 3/6 patients the max t value was inside the removedcortex.

Conclusion: BOLD responses were concordant with the lesion in 75%of patients with FCD detectable by MRI, and in 50% of patients with nor-mal MRI. Overall EEG/fMRI is able to non-invasively localize FCD in62.5% of cases. Supported by CIHR grant MOP-38079.

p704HOW MUCH LANGUAGE IS IN PICTURE AND FACEPROCESSING?A. Haag, M. Centeno, J. Stretton, C. Vollmar, M. Symms,M. K. Sidhu, B. Wandschneider, P. J. Thompson, J. Duncan, andM. KoeppUCL Institute of Neurology, London, UK

Purpose: Visual naming decline can occur after left (anterior) temporallobe (TL) resection. The risk cannot be fully predicted. Functional MRIactivations during picture processing of everyday objects and unfamiliarfaces were compared with a verbal (lexical) fluency (VF) task regardingactivation of language areas.

Method: 18 healthy controls (12 female, age: 31.4€6.0 years) viewedblocks of drawings of objects and unfamiliar faces during an fMRI task,and were asked to memorise them. Group activation maps were analysedon whole brain level (SPM8). Individual lateralisation indices (LIs) forthe contrast ‘‘pictures minus faces’’ were compared with LIs for VF.

Result: ‘‘Pictures minus faces’’ (p<.05 FWE) showed activation in theleft inferior temporal gyrus (ITG; Z=6.77), and (p<.001, uncorrected) inthe left inferior and superior frontal gyrus (Z=3.62; Z=5.79), which wasnot driven by deactivation during faces (exclusive masking). Lateralisa-tion indices showed left>right TL activation (LI< -0.2) in 15 subjects.Lateralisation was concordant with VF in 16 (88%).

Conclusion: Processing everyday objects vs. unfamiliar faces acti-vated frontal and parts of TL language networks. Lateralisation wasconcordant with VF. The ITG is typically activated in response tovisual language material. Activation within the left TL appeared poster-ior to the usual extent of TL resection in epilepsy. It remains to beshown, if naming decline can be predicted with object naming whenusing faces as a control condition. The paradigm may add to languagelateralisation in patients struggling with VF, and can be easily appliedin native language.

Psychiatry and Psychology 1Wednesday, 03 October 2012

p705PSYCHOSOCIAL AND PSYCHOPHARMACOLOGICALASPECTS OF A REFRACTORY PSYCHOGENICNONEPILEPTIC SEIZURESA. Rodriguez-Urrutia, F. J. Eiro� Orosa, S. G. Fidel Kinori, E.Santamarina, X. Salas-Puig, M. V. Lopez Craver, B. Bolivares,and M. ToledoVall d¢Hebron University Hospital, Barcelona, Spain

Purpose: We aim to describe the psychosocial and pharmacologicalaspects of patients with refractory psychogenic non-epileptic seizures(PNES).

Method: This was a cross-sectional study of consecutive patients withPNES referred to a Specialized Psychiatric Program from a tertiary Epi-lepsy Unit from January-2010 to January-2012. Refractoriness wasdefined as the presence of PNES despite a psychiatric treatmentapproach. Patients younger than 18 years-old and severe mental retarda-tion were excluded.

Result: Forty-eight patients were evaluated, 60% female. Average agewas 38 (€13) years-old. The time delay from the onset to the diagnosticwas 8 years. Epilepsy was comorbid in 30%. PNES semiology was mostlikely major motor (48%), followed by minor motor (32%) and non-motor(20%). Two or more semiologies coexisted in 35%. We identified dis-rupted family dynamics and environmental psychosocial stressors in morethan 60% of patients; despite, more than half were married, had childrenand 83% presented adequate family support. Professional or financialbenefits were identified in 30% Psychiatric history was present in 60%.However, no major psychiatric comorbidity or risk of suicidality wasfound. Most frequent psychiatric disorders were depression 30%, anxiety35% and adjustment disorder 8%. Patients were most likely treated com-bining two AEDs [0–8], Valproate (20%) and Levetiracetam (35%) werethe most commonly used. After the psychiatric intervention AEDsdecreased to a single one [0–5] that usually had psychiatric properties.

Conclusion: The PNES patients’ profile are young adults with disruptedfamily dynamics and environmental psychosocial stressors. The psychi-atric intervention influences the management of AEDs.

p706USE OF METHYLPHENIDATE FOR ATTENTION-DEFI-CIT/HYPERACTIVITY DISORDER IN CHILDRENWITH AND WITHOUT EPILEPTIFORM ABNORMALI-TIESD. Socanski*, and A. Herigstad�

*Stavanger University Hospital, Division of Psychiatry,Stavanger, Norway; and �Stavanger University Hospital,Stavanger, Norway

Purpose: The purpose of this retrospective study was to investigatewhether epileptiform abnormalites (EAs) recorded at the attention-defi-cit/hyperactivity disorder (ADHD) assessment and previous history ofepileptic seizures influence on initial use of methylphenidate for ADHD.

Method: Subjects were 517 ADHD children (82.4%male), agedbetween 5 and 14 years, mean 9.5+2.6, who were diagnosed between Jan-uary 2000 and December 2005. At least one standard EEG was performedon all patients. EEG findings were coded as either EEG with EAs or EEGwith non-EA. The group with EAs was compared with group withoutEAs and the use of methylphenidate as initial pharmacological treatmentfor ADHD symptoms was analyzed.

Result: The group with EAs consisted of 39 patients, 12 of them hadprevious history of epileptic seizures. Of 39 patients with EAs, 35(89.7%) patients were initially treated with methylphenidate. The groupwithout EAs consisted of 478 patients, 2 of them had previous history ofepileptic seizures. Active epilepsy was diagnosed in 13 out of the14patients, and 11 of the children had been seizure free for at least oneyear before ADHD assessment. There was no statistic differencebetween groups with and without EA where methylphenidate was usedas initial medication for ADHD. In addition, all patients with previousepilepsy were initially treated with methylphenidate. The epilepsy co-morbidity and occurrence of EAs were not a reason for not treatingADHD.

Conclusion: The EsA occurrence and epilepsy co-morbidity in childrendiagnosed with ADHD do not cause diminished initial use of methylphe-nidate for ADHD.

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p707PERCEPTION OF SIDE-EFFECTS IN EPILEPSYPATIENTS AND DEPRESSIONJ. Amlerova, and P. MarusicUniversity Hospital Motol, Prague, Czech Republic

Purpose: Side-effects of AED significantly influence quality of life inepilepsy patients. However the assessment is subjective and can be influ-enced by various factors. One of them can be depression which is themost frequent psychiatric comorbidity in epilepsy patients. The aim ofthe study was to compare the occurrence of side-effects and depressionand to assess if there is any correlation between these two parameters.

Method: 158 epilepsy patients were included in the study. The patientswere screened for depression with the help of Beck Depression Inventory(BDI) and shortened version of depression questionnaire (NDDI-E, Gil-liam F et al., 2006). The occurrence and the perception of side-effectswas assessed by structured questionnaire covering both for somatic andpsychical side-effects.

Result: Criteria for the diagnosis of depression were met by 18% of allpatients according to BDI and by 25% according to NDDI-E. Strong cor-relation was found between both tests (BDI, NDDI-E) – Pearson corr.0.542; p = 0.01. The most frequently reported side-effects were fatigue(58%), irritability (50%), memory impairment (46%) and dysphoria and/or sadness (46%). These side-effects were also perceived by patients asthe most significant. No correlation was found between depression andoccurrence or perception of specific type of side-effect.

Conclusion: Side-effects of AED and their perception seem to be notdirectly influenced by the level of depression. Both these variables can beconsidered as independent factors which significantly influence qualityof life in epilepsy patients. To identify them in routine clinical settingshort structured questionnaires can be used.

p708DURATION OF INTERICTAL PSYCHOTIC EPISODESBY ANTIPSYCHOTIC DRUG TREATMENTSK. Hara*, N. Adachi�, N. Akanuma�, M. Okazaki§, M. Ito–,M. Kato**, and T. Onuma***Asai Hospital, Togane, Japan; �Adachi Mental Clinic,Sapporo, Japan; �South London and Maudley NHS FoundationTrust, London, UK; §National Center Hospital of Neurology andPsychiatry, Kodaira, Japan; –Jozen Mental Clinic, Sapporo,Japan; and **Musashino Kokubnji Clinic, Kokubunji, Japan

Purpose: Patients with epilepsy often suffer from coexisting interictalpsychotic (IIP) symptoms. However, the treatment systems of these phe-nomena have not been well established due to insufficient evidence. Weretrospectively investigated relation between duration of IIP episode andantipsychotic drug (APD) treatments.

Method: In our adult epilepsy clinics, 155 patients with epilepsy (age ofonset of epilepsy was mean 12.4 years; epilepsy types comprised 25 gen-eralized epilepsy and 130 partial epilepsy) exhibited 320 IIP episodes(age of the psychotic episodes was mean 30.9 years). Duration of theseIIP episodes was retrospectively analysed. The APD treatments of the320 IIP episodes comprised four groups: 242 episodes were treated withtypical APDs (Typical group), 15 with atypical APDs (Atypical group),15 with both typical and atypical APDs (Mixed group), and 48 were nottreated with APD (Non-APD group). The dosage of APDs undertakenwas converted into chlorpromazine equivalent.

Result: Duration of the IIP episodes were mean 82.7 weeks. There wasno significant difference in the duration of IIP episodes between the fourtreatment group; Typical group lasted for mean 91.8 weeks, Atypicalgroup for 101.5 weeks, Mixed group for 90.5 weeks, Non-APD group for28.9 weeks (F=1.46, p=0.224). In 272 episodes treated with APDs, a total

chlorpromazine-equivalent dosage of the APDs ranged from 12.5 to 3425mg/day (mean 454.7, SD 534.0).

Conclusion: Our findings suggest that any types of APD can be used forthe treatment of IIP episodes in patients with epilepsy.

p709COMORBID DEPRESSION IN EPILEPSY – SOCIODE-MOGRAPHIC AND CLINICAL CORRELATES ANDIMPACT ON QUALITY OF LIFEK. S. Todorova, and A. G. KaprelyanMHAT ‘‘St Marina’’, Varna, Bulgaria

Purpose: To investigate certain sociodemographic and clinical corre-lates of comorbid depression in a sample of adult Bulgarian patients withepilepsy and to assess simultaneously the role played by mood, seizure-related and sociodemographic variables in determining their perceptionof QOL.

Method: All 126 adult patients with a diagnosis of idiopathic epilepsyunderwent clinical psychiatric examination. ILAE classification for epi-lepsies and epileptic syndromes was used. Comorbid depressive disorderwas diagnosed according to ICD-10 diagnostic criteria, followed by eval-uation on Hamilton Depression Rating Scale (HAM-D-17). Self-asses-ment scales were administered: Seizure Severity Questionnaire (SSQ)and Quality of Life in Epilepsy Inventory-31 (QOLIE-31). A question-naire for demographic and seizure-related variables was completed. Uni-variate and multivariate regression analyses were performed to explorethe association between possible prognostic independent variables andQOLIE-31 overall and subscale scores.

Result: Comorbid depressive disorder affected 36(28.6%) of all evalu-ated patients. Education, seizure severity and duration of epilepsy corre-lated significantly with comorbid depression. Following the univariateanalysis education, employability and age, seizure severity and seizure fre-quency and the severity of the comorbid depressive disorder were the vari-ables significantly correlated with QOLIE-31 overall score (p<0.01). Athree variable model accounted for 74% of the variance for QOLIE-31overall score including seizure severity, comorbid depression and seizurefrequency.

Conclusion: Comorbid depressive disorder in a sample of adult Bulgar-ian patients with epilepsy was associated with low education, severe sei-zures and longer duration of epilepsy. Detection and treatment ofpsychiatric comorbidity in epilepsy is a challenge for improving the qual-ity of life of the affected patients.

p710PSHYCHIATRIC FEATURES IN FAMILIES WITHAUTOSOMAL DOMINANT CORTICAL TREMOR,MYOCLONUS AND EPILEPSYL. Santulli, A. Coppola, C. Caccavale, C. Ciampa, P. Striano,and S. StrianoEpilepsy Center Federico II, Naples, Italy

Purpose: Autosomal Dominant Cortical Tremor, Myoclonus and Epi-lepsy (ADCME) is an inherited condition characterized by familialoccurrence of cortical tremor, myoclonus and epileptic seizures. We haverecently reported a relatively high frequency (>40% of the cases) of pshy-chiatric symptoms clinically defined (i e generalized anxiety disorderand depression) in a large series of patients. Aim of this study is to furtherassess pshychiatric comorbidity in a subgroup of ADCME/BAFMEpatients by using reliable and valid pshycodiagnostic scales.

Method: Thirteen patients underwent self administered tests: BDI (BeckDepression Inventory), STAI-Y (State-Trait Anxiety Inventory Y),MMPI-2 (Minnesota Multiphasic Personality Inventory-2) and QoLIE-31 (Quality-of-Life in Epilepsy Inventory), and a pshychiatric interview.

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Result: Severe to mild depression symptoms were present in almost allthe patients whereas a clinically relevant anxiety disorder was evident ineight. MMPI-2 results supported the coexistence of a personality disorderin seven patients. Quality of life scores were lower than previouslyreported in Italian epileptic patients.

Conclusion: This pilot study firstly confirms a high incidence of mooddisorders, particularly depression and anxiety, in ADCME patients, oftenassociated to pathological traits of personality. Moreover these patientsshow a worse quality of life compared to other patients presenting only withseizures, probably due to the influence of tremor on daily life activities.

p711INFLUENCE OF PSYCHOPATHOLOGIC SYMPTOMSON QUALITY OF LIFE IN PATIENTS WITH EPILEPSYM. Milovanovic, Z. Martinovic, V. Radivojevic, M. Jovanovic,N. Buder, and R. DjokicInstitute for Mental Health, Belgrade, Serbia

Purpose: To assess psychopathologic symptoms in patients with epi-lepsy and to define its influence on quality of life (QOL).

Method: Adult patients (age range 18–65 years) with epilepsy of normalintelligence, without any progressive neurological disease or psychoticdisorder were included in the study. They completed The SymptomChecklist-90-Revised (SCL-90-R) - self-report multidimensional ques-tionnaire designed to screen psychological problems, and Quality of lifein epilepsy Inventory (QOLIE-31 - Serbian validated version; Seizure,2010).

Results: 202 patients completed the questionnaires. Compared topatients with primarily generalized epilepsies, patients with localization-related epilepsies showed significantly higher scores on SCL-90 primarysymptom dimensions: Somatization, Obsessive-Compulsive, Interper-sonal Sensitivity, Depression, Anxiety, Hostility, Phobic Anxiety, Para-noid Ideation, and Psychoticism (t=2.28–3.66; p=0.025–0.000). One-way ANOVA showed that Obsessive-Compulsive, Interpersonal Sensi-tivity, Depression, Anxiety, Hostility, Paranoid Ideation, and Psychoti-cism scales were higher in patients with high seizure severity index(F=2.793–4.286; p=0.043–0.006). QOLIE-31 scales: Overall quality oflife, Emotional well being, Fatigue, Cognitive and Social function weresignificantly negatively correlated to all SCL-90 scales (rho=-0.745,p<0.001). Also, there was negative correlation between QOLIE-31 Medi-cation effect scale and SCL -90 Obsessive-Compulsive and Psychoticismscales. Multiple regression analysis showed that 49.4% of overallQOLIE-31 score was predicted by SCL-90 scales (F=11.4; p<0.001; R2=0.494). Tests of regression coefficients significance showed that Obses-sive-Compulsive scale score (beta =-0.28; t=-1.99; p<0.05) and depres-sion scale score (beta =-0.43; t=-2.69; p<0.01) were significantpredictors of quality of life.

Conclusion: Psychopathologic symptoms frequently coexist in patientswith localization-related epilepsy, with high seizure severity, and havesignificant influence on QOL.

p712FORCED NORMALIZATION IN POST-SURGICALPATIENTS OF TEMPORAL LOBECTOMY AND MEDI-CALLY INTRACTABLE EPILEPSY. COLOMBIANFOUNDATION CENTER FOR EPILEPSY AND NEURO-LOGICAL DISEASES – FIREM. Z. Torres, E. V. Perea, J. FandiÇo-Franky, L. V. Polo,R. O. Guerra, S. C. PiÇa, J. C. I. Benedetti, O. B. Cabarcas,D. J. Jimenez, E. C. Garcia, and T. Y. RodriguezColombian Foundation Centre for Epilepsy and NeurologicalDiseases, Cartagena, Colombia

Purpose: To identify associated factors with the development of forcednormalization (FN) in post-surgical patients of temporal lobectomy (TL)with medically intractable epilepsy (MIE).

Method: A cohort study analytical-descriptive, retrospective, weselected 248 medical records of patients who met epilepsy surgery proto-cols, 22 of which showed disappearance of seizures with alternating psy-chiatric disorders after postsurgical TL, we divided group 1 with the oneswho presented FN and those who did not have these features were classi-fied as group 2.

Result: Group 1 showed a percentage of (77.2%) with tendency tofemale predominance (p <0.05), group 2 obtained (50.44%) (p <0.05)95% CI (1.47–1.59). In the FN group, 19 cases (86.4%) were detectedin patients with duration of epilepsy greater than 10 years and 168(74.3%) in group 2. Psychosis and depression predominated with a dis-tribution of group 1 (54.5%) SD + / - 1.43, (p> 0.05) and group 2(5.8%), SD + / - 1.50, (p>0.05) 95% CI (4.87–5.32). For epileptiformactivity, the discharges were identified bilateral in group 1 (90.9%) + / -0.29 (p> 0.05), group 2 (20.8%), SD + / - 0.40, (p <0.05) 95% CI (1.21–1.33).

Conclusion: The forced normalization phenomenon is related to thetime course of epilepsy (more than 10 years), predominantly in thefemale gender and with a psychopathology of both psychotic anddepressive type. Bilateral epileptiform discharges constitutes anotherfinding to take into account, suggesting that psychiatric alterations aremasked by epilepsy, manifesting themselves in order to gain controlof it.

p713ARE PSYCHIATRIC DISORDERS EXCLUSION CRITE-RIA FOR VIDEO EEG MONITORING AND EPILEPSYSURGERY IN PATIENTS WITH MESIAL TEMPORALSCLEROSIS?P. O. Da ConceiÅ¼o, P. P. Do Nascimento, N. B. Alonso,E. M. T. Yacubian, and G. M. De Araffljo FilhoUniversidade Federal De Sao Paulo – UNIFESP, S¼o Paulo, SP,Brazil

Purpose: Epilepsy surgery (ES) is a treatment option for patients withrefractory temporal lobe epilepsy (TLE). However, psychiatric disor-ders (PD) have been a contraindication for pre-surgical evaluation andsurgeryin many epilepsy centers. The aim of this study was to evalu-ated safety of Video EEG (VEEG) and surgical outcome in patientswith refractory TLE and mesial temporal sclerosis (TLE-MTS) associ-ated with PD.

Method: We retrospectively analyzed clinical, sociodemographic,VEEG data and surgery outcome from patients with refractory TLE-MTS who underwent ES over the period of 2002 to 2011, and comparedthe data between patients with and without PD. Psychiatric evaluationwas performed through DSM-IV criteria. Safety during pre-surgical eval-uation was analyzed by the rate of adverse events (AEs), and the surgicaloutcome was measured through Engel's classification.

Result: We evaluated 145 patients (82 females, mean age 37.8 years,range 18–63), 61 with PD. The mean of stay in VEEG was 99.66 hoursand was not affected by PD. In patients with PD, 4.91% (3/61) had AEs,13.11% (8/61) had nonepileptic attack disorders (NEADs). Amongpatients without PD, 4.76%(4/84) had AEs and 5.95% (5/84) had NE-ADs. In the first two years of follow up in 94 patients who underwent ES,65.85% (27/41) with PD and 67.92% (36/53) of group without PDbecame free of disabling seizures (Engel I).

Conclusion: These data demonstrate that the rate of AEs and the seizureoutcome did not differ significantly between both groups, reinforcing thatPD should not be absolute exclusion criteria for VEEG monitoring andepilepsy surgery.

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p714MOOD DYSFUNCTION IN EPILEPSY PATIENTS IN KO-SOVOV. Govori*, S. Vranica*, M. Berisha�, B. Berisha*, andD. Zajmi�

*University Clinical Center of Kosovo, Pristina – Kosovo,Albania; and �National Institute of Public Health of Kosovo,Pristina – Kosovo, Albania

Purpose: Mood disorders are the most frequent psychiatric co morbidityin epilepsy. The aim of this study is to determine the presence of depres-sive symptoms in epilepsy patients.

Method: In this prospective study, 76 consecutive outpatients withactive epilepsy were examined in the Department of Neurology of Ko-sovo during 2011. Clinical data for patients included age, gender, seizuretype, education, employment, marital status. The epilepsy evaluation wasdone on standard digital EEG recordings. We used the Beck DepressionInventory test to evaluate depressive symptoms in patients with epilepsy.The test contained 21 questions each answer being scored on scale valueof 0 to 3. Scores of 11–15 are indicative of mild, 16–24 of moderate, and24 of severe depression. All data collected were analyzed and calculatedrelevant statistical parameters and tests for the level of significance forP<0.01 and P<0.05.

Result: From 76 patients with epilepsy 52% were male, average age was33.4 € 13.54. Partial type of epilepsy in 64.0% of cases, severe depressivesymptoms in 32.0% and moderate depressive symptoms in 29.3%, 12.0%think about suicide but had not made, with statistical significance forP<0.05. From overall number of examined outpatients with epilepsy,unemployed were in 89.3% of cases with statistical significance forP<0.0001.

Conclusion: Our study suggests that patients with epilepsy are atincreased risk for depression, vigilant approach and early treatment isneeded.

p715MEMORY DEVELOPMENT IN CHILDREN WITH AHISTORY OF PROLONGED FEBRILE SEIZURESM. Martinos, S. Pujar, H. O’Reilly, R. Scott, R. Chin, and M. DeHaanUCL, London, UK

Purpose: Retrospective studies have highlighted an association betweenhippocampal sclerosis and a childhood history of prolonged febrile sei-zures (PFS). Given the well established role of the hippocampus in mem-ory, we would therefore hypothesize that memory impairments may bepresent in children with a history of PFS.

Method: We are recruiting children with a history of PFS originallyidentified by the population-based North London Convulsive Status Epi-lepticus in childhood surveillance study (NLSTEPSS). Upon recruitmentchildren undergo detailed investigations to determine their longer-termoutcome 6–10 years following their episode. Memory abilities areassessed using the Children's Memory Scale (CMS) and full scale IQ(FSIQ) is assessed using the Wechsler Abbreviated Scale of Intelligence(WASI).

Result: Nineteen children (mean age: 9 years) have so far completed afull set of investigations a mean of 7.21 years following their episode.Their general memory quotient falls within the normal range (mean:103.7), and is highly correlated with their FSIQ (r=0.595, p=0.007). In 3children, there is evidence of statistically significant discrepanciesbetween their visual and their verbal memory domains pointing to thepossibility of structural abnormalities. Finally, one child was found to beclinically impaired in their immediate and delayed verbal memoryabilities.

Conclusion: On the whole children with a history of PFS have memoryabilities that place them within the normal range and are tightly linked totheir intellectual abilities. Isolated cases where there are indications ofspecific memory impairments need to be evaluated further to establishwhether this is of clinical importance.


p716RHYTHMIC TREMOR ARTIFACT MIMICKING ICTALEPILEPTIFORM PATTERN ON EEG OF NON-EPILEP-TIC PSYCHOGENIC SEIZUREST. Tombul, and A. MilanliogluY�z�nc� Yil Universty, Van, Turkey

Purpose: Psychogenic seizures are events which observed commonly innon-epileptic seizures, and can be confused with epileptic seizures in-terms of motor phenomena when an adequate clinical and electrophysio-logical assessment are not done. In our study, we aimed to determinecharacteristics of EEG that can be mixed confused with ictal epileptiformactivities of non-epileptic psychogenic seizures characterized by rhyth-mic movements similar to tremor.

Method: The cases with non-epileptic psychogenic seizures havinglike clonic convulsions, rhythmic movements evaluated clinically andbased on electrophysiological characteristics. Five cases, three men andtwo women, aged between 33 and 54, were included into the presentstudy.

Result: Three of these cases had only psychogenic, and the remaininghad both psychogenic and complex partial type of epileptic seizures. Inictal recordings, rhythmic tremor artifacts that were similar to seizureactivity composed of sharp-contoured theta waves were recognized. Thispattern was appeared by theta-like activity with stable frequency, suddenonset/offset without building-up and postictal slowing. In synchronizedvideo recordings, rhythmic tremor movements which were similar to clo-nic contractions were demonstrated at upper and lower extremities, andsometimes at the head and trunk.

Conclusion: Psychogenic seizures may be characterized by rhythmicmovements that are similar to clonic contractions, and the activityobserved in the meantime may mimic ictal discharges observed in theepileptic seizures. However, the frequency of electrophysiologic patternof non-epileptic seizures showed narrow interval changes and most of thetime remained stable. In such cases, the detailed semiological and elec-trophysiological evaluation with a large number of seizure recordings areimportant.

p717DO ANTIPSYCHOTIC DRUGS INCREASE SEIZUREFREQUENCY IN EPILEPSY PATIENTS?M. Okazaki*, N. Adachi�, M. Ito�, M. Watanabe*, Y. Watanabe*,M. Kato§, and T. Onuma§

*National Center Hospital of Neurology and Psychiatry,Kodaira, Japan; �Adachi Mental Clinic, Sapporo, Japan; �JozenMental Clinic, Sapporo, Japan; and §Musashino KokubnjiClinic, Kokubunji, Japan

Purpose: Patients with epilepsy could suffer psychosis and related con-ditions. It is sometimes difficult to use anti-psychotic drugs (APDs) for

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the treatment of these conditions, because APDs may have risks to aggra-vate seizures. However, evidence whether the treatment with APDsincreases seizure frequency significantly in epilepsy patients who arealready being treated with antiepileptic drugs (AEDs) is scarce. To inves-tigate the clinical effects of APDs on the seizure frequency of epilepsypatients, we retrospectively evaluated the one-year prognosis of seizurefrequencies.

Method: The subjects of the study were 142 epilepsy patients treatedwith APDs (typical APD in 107, atypical APDs in 68 and combination in33) and 291 age-, age at onset of epilepsy- and epilepsy type–matchedepilepsy patients without APD treatment. Seizure frequencies in a one-year period after administration of APDs were retrospectively evaluatedand compared with those of the controls.

Result: In the epilepsy patients with APDs, the seizure frequencies atfour observation points (1-, 3-, 6-, and 12-months after their adminis-tration of APDs were lower than those of the same four age-matchedperiods of the control group. There was no significant difference in sei-zure frequencies among typical APDs, atypical APDs, and the combi-nation of typical/atypical APDs. In epilepsy patients treated withAEDs, APDs are unlikely to exacerbate seizures. Most APDs, eithertypical or atypical, can be used for psychiatric treatment in epilepsypatients.

p718PSYCHOGENIC NON EPILEPTIC SEIZURES: THENIDUS MAY LIE SOMEWHERE ELSES. Kumar*, and P. K. Singh�

*CSMMU (Erstwhile King George's Medical College),Lucknow, Patna, India; and �Patna Medical College, Patna,India

Purpose: Psychogenic Non Epileptic Seizures (PNES) has graduallylost its place from the body of literature in the developed world. But theimportance of diagnosis and management of the conditions can't beundermined. The condition is often misdiagnosed even at the tertiary carecentres. The co-morbidities associated with PNES is often ignored due tothe dramatic nature of the presentation of the illness, by even the mostexperienced clinicians. The study aimed at finding the co-morbid ill-nesses which often form the background of the illnesses. Having theunderstanding of the co-morbid condition can be crucial to the manage-ment as it may save the health costs and prevent the unnecessary institu-tion of the medications. The nature of the stress can vary across theboundaries but not the phenomenology or the associated psychopathol-ogy in case of PNES.

Method: Fifty consenting patients diagnosed with Non Epileptic Sei-zures who attended psychiatry OPD of Patna Medical College, Bihar,India were assessed for co-morbidities clinically and history was alsoobtained from closely living family member of the patient. Eighty per-cent of the patients were found to be harbouring co morbid psychiatric ill-nesses. Most common being Depression followed by Anxiety disorders.The other disorders present included Adjustment Disorder, Personalitydisorders and rarely Psychosis.

Result: It was inferred that Co-morbid Psychiatric illnesses are com-monly associated with Non Epileptic Seizures. Finding and treating theCo-morbid Psychiatric illnesses can help formulating effective manage-ment strategies and hence better outcomes in patient with PsychogenicNon Epileptic Seizure Disorder.

Conclusion: The presentation and hence the diagnosis of PNES can bedeceptive. Understanding the phenomenology and the underlying psy-chopathology is important for avoiding the possible error of judgmentand managing the same. The series revealed co-morbid psychopathologyin sizeable no of patients suffering from PNES.

p719INTERICTAL DYSPHORIC DISORDER IN JAPANESEPATIENTS WITH LOCALIZATION-RELATED EPI-LEPSY: PREVALENCE AND CLINICAL CHARACTER-ISTICSA. Yoshino, Y. Tatsuzawa, T. Mogi, T. Suda, and S. NomuraNational Defense Medical College, Tokorozawa, Japan

Purpose: Researchers in European countries and the United State sug-gested the occurrence of a pleomorphic affective syndrome in patientswith epilepsy named interictal dysphoric disorder (IDD). We estimatedthe prevalence of IDD in Japanese patients with localization-related epi-lepsy using the Japanese version of the Interictal Dysphoric DisorderInventory (IDDI, Mula et al., 2008) and investigated the clinical charac-teristics of IDD.

Method: Eighty-seven patients with localization-related epilepsy (med-ian age 39 years; female, 39) were assessed using IDDI, Quality of Life-26 (WHO-QOL26), Hamilton Depression Rating Scale (HAM-D),Adverse Events Profile (AEP), and Mini Mental State Examination(MMSE). Diagnosis of current and lifetime psychiatric disorders wasestablished using the Mini International Neuropsychiatric Interview(MINI). We also evaluated to what extent IDD and premenstrual dys-phoric disorder (PMDD) overlapped.

Result: The internal consistency of the Japanese version of IDDI wasfairly good (Cronbach's alpha, 079). The prevalence rate of IDD was esti-mated 38.0% without sex difference. Only 13.3% of the female patientswith IDD met the criteria of PMDD. Compared with the patient withoutIDD, the patients with IDD were more likely to have any current and life-time psychiatric disorders (lifetime, 60.6% vs. 33.3%). WHO-QOL26score was significantly less and HAM-D and AEP scores were signifi-cantly greater in the patients with IDD. However, the seizure-free rate andMMSE score were not different between patients with and without IDD.

Conclusion: These results suggest that more than one third of patientswith localization-related epilepsy suffer from IDD which might impairtheir QOL and have some clinical and psychopathological characteristics.

p720PREVALENCE OF SYMPTOMS OF INTERICTAL DYS-PHORIC DISORDER: RESULTS OF A SURVEY CON-DUCTED AT THE WELSH EPILEPSY UNITC. B. Kuloor*, and Z. Ahmed�

*South London & Maudsley NHS Foundation Trust, London,UK; and �University Hospital of Wales, Cardiff, UK

Purpose: Interictal Dysphoric Disorder (IDD) is considered to be a com-mon yet under-diagnosed neuropsychiatric disorder in epilepsy. The aimof this study was to explore the prevalence of individual symptoms of In-terictal Dysphoric Disorder among patients with epilepsy attending a spe-cialist epilepsy unit.

Method: One hundred two consecutive adult patients with epilepsy wereinvited to complete the Interictal Dysphoric Disorder Inventory, a 38-itemself-report questionnaire. Patients with an established psychiatric diagno-sis or co-morbid medical conditions with symptoms resembling those ofIDD and patients with special needs were excluded from this study.

Result: Eighty-eight patients completed the questionnaire (response rateof 86%). Most patients had experienced at least one symptom of IDD ofsignificant severity over the previous 12 months. Anergia was the mostcommonly reported symptom (prevalence rate of 56%), followed by irri-tability (47%), anxiety (41%), pain (41%), fear (41%), depressed mood(40%), and insomnia (34%). Euphoric mood was the least reported symp-tom (10%). Nearly 24% of patients fulfilled the criteria for a diagnosis ofIDD. Furthermore, one in four patients recognised a temporal relation-ship between changes to their anti-epileptic drug (AED) therapy and theemergence of symptoms of IDD.

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Conclusion: Symptoms of IDD are prevalent among patients with epi-lepsy and may go unrecognised. The prevalence rate for IDD in our studywas higher than the rate reported in the only other cross-sectional studypreviously conducted. Effect of changes to AED therapy on the emer-gence of symptoms of IDD warrants further exploration.

p721QUALITY OF LIFE IN CHILDHOOD EPILEPSY ANDPARENTAL AND PAEDIATRIC ANXIETY: THE ROLEOF A STRUCTURED EDUCATION PROGRAMG. Serdaroglu, S. Sahin, B. Ozbaran, S. Yilmaz, A. Akcay,H. Tekgul, and S. GokbenEge University Faculty of Medicine, Izmir, Turkey

Purpose: To determine whether a structured education program canchange anxiety and quality of life in children with epilepsy, and reduceparental anxiety.

Method: Three groups were included: Group I, 6 - 18 year old newlydiagnosed epilepsy patients; Group II, patients with epilepsy having fol-lowed-up and on antiepileptic therapy for at least 1 year; Group III,patients with intractable epilepsy. Questionnaires were applied before and6 months after a program of education in the first group. Applied testswere; questionnaires about epilepsy, anxiety scales (‘State-Trait AnxietyInventory’, ‘Anxiety Scale for Children’ for the child), ‘Quality of LifeScales’ and the ‘Child Behavior Check List’. These tests were also appliedto the children in Groups II and III during their outpatient clinic visit.

Result: Seventy-two epileptic children and their parents were included inthe study. Post-education scores of Group I were higher than their pre-edu-cation scores and the scores of the other 2 groups. After education, a signif-icant decrement was seen both in state and trait scores of the ‘State-TraitAnxiety Inventory’ which evaluated parental anxiety. ‘Anxiety Scale forChildren’ had also a decrement for Group I after education. Child Qualityof Life Scales were evaluated. ‘Scale Total Scores’ and ‘PsychosocialHealth Total Scores’ were significantly higher in the post-educationassessment when compared to the pre-education assessment for Group I.

Conclusion: Giving information about epilepsy will decrease anxietylevels, increase drug compliance and possibly provide better seizure con-trol in children with epilepsy.

p722A LONGITUDINAL STUDY OF PSYCHOLOGICAL FEA-TURES IN PATIENTS BEFORE AND 2 YEARS AFTEREPILEPSY SURGERYK. Malmgren, and E. EngmanSahlgrenska Academy, University of Gothenburg, Gçteborg,Sweden

Purpose: There are few consistent findings concerning psychologicaland personality features in patients with drug resistant epilepsy. Thisstudy aimed at investigating psychological features in patients before andtwo years after epilepsy surgery.

Method: Fifty patients, 39 with temporal lobe epilepsy (TLE) and 11with frontal lobe epilepsy (FLE) were assessed at baseline and two yearspostoperatively with the Karolinska Scales of Personality (KSP). Thisinventory consists of 15 scales (135 items). Each item is given a state-ment with four-point Likert scale response format with normative databased on a large random healthy adult sample of 400 men and women.

Result: Baseline group level outcome was normal, while individuallevel analyses delineated psychological problems outside the normalrange in subsets of patients. Features of hostility characterised half of theFLE and one fourth of the TLE patients. Above 1/3 in each group haddependency features. About 1/3 of the TLE patients suffered from psych-

asthenia. There was an association between higher baseline seizure fre-quency and higher scores in the Suspicion Scale for TLE patients. Theshifts in T-score mean levels from baseline to the two year follow-upwere all within the normal range.

Conclusion: In this cohort, even though group levels were normal a sub-stantial number of patients had psychological problems. The main longi-tudinal result was that the personality features were stable and did notchange after epilepsy surgery.

p723THE EFFECTS OF SUPPORT GROUP ON SELF-ESTEEM IN PEOPLE WITH EPILEPSYS. Tiamkao*, K. Sawanchareon�, and S. Pranboon�

*Integrated Epilepsy Research Group, Khon Kaen University,Khon Kaen, Thailand; �KhonKaen University, KhonKaen,Thailand; and �Srinagarind Hospital, KhonKaen University,KhonKaen, Thailand

Purpose: People with epilepsy (PWE) have to face physical and mentalillness, and social stigma, which affect their self – esteem and quality oflife.

Objective: The purpose of this study was to examine the effects of a sup-port group on self-esteem in PWE.

Method: A Quasi-experimental study was performed of 120 PWE in anEpilepsy Clinic at Srinagarind Hospital. An experimental group (N=60)attended in the support group before receiving regular healthcare ser-vices. The control group (N=60) received only regular healthcare ser-vices. Data was collected by using the Rosenberg self -esteem scalescoring before and after the experiment. The score was analyzed by usinga paired t-test and an independent t-test.

Results: The study showed that before the experiment, the self –esteemscore of the control group was significantly higher than the experimentalgroup (= 35.06, 32.80, t = 2.38 P < .05). After the experiment, the score ofthe control group and the experimental group were showed a significantstatistical difference (= 3.06, 34.30, t = -6.61 P < .05). The score in thecontrol group was significantly lower than the experimental group (=35.01, 30.60, t = 9.97 P < .05), while the score in the experimental groupwas significantly higher than before the experiment

(= 32.80, 34.30, t = 2.19 P < .05)

Conclusions: The support group improves in self- esteem in PWE. Med-ical personnel should set up a support group for PWE to enhance theirself-esteem.

p724COGNITIVE RETRAINING AMONG CHILDREN WITHEPILEPSY AT A TERTIARY CARE HOSPITAL INDELHI, INDIAK. Bala, V. Sharma, and N. VermaInstitute of Human Behaviour and Allied Sciences, Delhi, India

Purpose: Current study was an attempt to find out the effect of cognitiveretaining on the most commonly affected cognitive domains ie. attentionand memory among children with epilepsy receiving AEDs.

Method: Children diagnosed with idiopathic epilepsy were selectedfrom outpatient department of neurology at IHBAS. Participants weredivided in to two experimental groups and a waitlist control group. GroupA (ongoing seizure), group B (seizure free), group C (wait list controlgroup). All these children were assessed on various domains of attentionand memory. Between pre and post assessment they were provided with apackage of 24 sessions of cognitive retraining:

Result: Findings revealed no significant difference in the cognitiveskills of the children among three groups in pre intervention condition

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except for sustained attention Post intervention condition of experimentalgroups resulted in significant improvement in most of the cognitive skills.No such gains were observed for the wait list control group. It wasobserved that children with seizure free condition performed better onassessment and showed higher gain from cognitive retraining as com-pared to those with ongoing seizures.

Conclusion: It was inferred that manualized cognitive retraining pack-age is an effective module for enhancing cognitive skills of children suf-fering from cognitive deficits resulting from epilepsy.

Conclusion: The study inference was that manulisized cognitive retrain-ing package is an effective module for enhancing cognitive skills of chil-dren suffering from cognitive defecits associated with epilepsy.

p725ONLINE ASSESSMENT OF REMOTE AND SEMANTICMEMORY IN EPILEPSY BY USING DAILY NEWSQUESTIONNAIRESM. Hendriks*, T. Lunenburg�, and M. Meeter�

*Epilepsy Centre Kempenhaeghe, Heeze, The Netherlands;�Radboud University Nijmegen, Nijmegen, The Netherlands;and �Free University, Amsterdam, The Netherlands

Purpose: Although anterograde memory deficits are well documentedin patients with epilepsy, the extent to which remote memory deficitsoccur is less clear. This is due in part to a lack of reliable methods forassessment. A common method to assess remote memory is an autobio-graphical memory test. The primary purpose of this study is to compareremote, semantic memory in patients with epilepsy and healthy controls.

Method: In cooperation with the Dutch Epilepsy Society (EVN) in total420 epilepsy patients and 260 healthy controls logged in at the EVN web-site to fill in the Amsterdam Media Questionnaire (AMQ) and the DailyNews Memory Test (DNMT) (Meeter, et al, 2004, 2005). 509 Partici-pants (age between 16 and 83) were included to the DNMT sample and429 Participants (age between 24 and 83) were included to the AMQ sam-ple. Paticipants had to anwer the questionnaires per decade after their sei-zure onset.

Result: The results show that healthy Controls score significantly betteron the AMQ compared to Epilepsy Patients (F(1,164) = 14.864, p<.001,v2=.083. Healthy Controls score significantly better for all 3 decades ofthe DNMT compared to Epilepsy Patients (F(1,503) = 8.392, p=.004,v2=.16). An ANCOVA did not show statistically significant effects of theepilepsy related factors.

Conclusion: This study demonstrates memory problems for news factsin patients with epilepsy. We found no evidence for epilepsy related fac-tors with remote memory. The results of the current study show a prob-lem in the recall of memories.

p726LONG TERM MEMORY OUTCOME AFTER SELEC-TIVE AMYGDALOHIPPOCAMPECTOMY VERSUSSTANDARD TEMPORAL LOBECTOMY IN TEMPORALLOBE EPILEPSYA. Wendling, I. Wisniewski, C. Davanture, J. Zentner, S. Bilic,A. M. Staack, M. Valenti, A. Schulze-Bonhage, P. Kehrli,E. Hirsch, and B. J. SteinhoffKork Epilepsy Centre, Kork, Germany

Purpose: To investigate the long term follow-up after selective amyd-alohippocampectomy (SAH) and standardized temporal lobectomy(STL), respectively, in two homogeneous patient groups with clearlydefined unilateral mesial temporal lobe epilepsy (mTLE). SAH was

performed in a German patient cohort, STL in a French group. The surgi-cal procedure was performed since it had been standard in each centre.

Method: We retrospectively recruited 60 adult patients with medicallyrefractory mTLE with unilateral hippocampal sclerosis which had justi-fied temporal lobe surgery between 2000 and 2009 and were seizure freeafter resection. Neuropsychological assessments were performed in allthese patients on three different occasions by using parallel versions ofstandardized neuropsychological tests (preoperatively, 1 year postopera-tively and on average 7 years postoperatively).

Result: On the 7 years postoperative examination, SAH patients had sig-nificantly better performances than STL patients concerning visual learn-ing and delayed recall, verbal and visual short term memory and visualworking memory.

Conclusion: SAH appears to be the best surgical method to treat drug-resistant mesio-TLE with unilateral hippocampal sclerosis in regardinglong term memory function.


p727TYPES OF COPING STRATEGIES FOR EPILEPTICPATIENTSL. Lipatova, L. Vasserman, and A. ChuykovaSt.Petersburg V.M. Bekhterev Psychoneurological ResearchInstitute, St. Petersburg, Russian Federation

Purpose: Explore the types of coping strategies (CS) for epilepticpatients (EP) to overcome difficult situations in the different areas of life.

Method: 139 EP aged 19 to 65 years (72 women and 67 men) wereexamined with a CS test (Lazarus R.S., Folkman S., 1986; VassermanL.I. et al., 2009).

Result: EP most frequently used CS options that facilitated successfuladaptation and expressed in individual's active behavior towards resolv-ing difficult situations: problem solving (62%), seeking social support(60%), exercising self-control (59%), accepting responsibility (53%) andpositive reappraisal (49%). Maladaptive CS types were less common forEP – ‘‘confrontation’’ – in 42%, ‘‘distancing’’ – 41% and ‘‘escape-avoid-ance’’ -38%. Differences in CS between male and female patients wererevealed: men more frequently than women took the strategies of‘‘accepting responsibility’’ (60% and 44% respectively), ‘‘positive reap-praisal’’ (58% and 52%) and ‘‘problem solving’’ (67% and 62%), how-ever, they were more likely to distance (50% and 45%). Women on theother hand were more likely to use maladaptive emotional and behavioralCS – ‘‘confrontation’’ (51% women, 42.9% - men) and ‘‘ escape-avoid-ance’’ (44% and 41% respectively).

Conclusion: EP use a wide range of CS: from active strategies aimed atanalyzing and resolving problems as they occur, to passive forms ofbehavior that contribute to continuous emotional stress and problemavoidance. Besides the presence of gender-specific choices of CS thisstudy shows the prevalence of the EP with adaptive forms of copingbehavior aimed at the collaboration with the attending doctor and facili-tating social adaptation.

p728COGNITIVE IMPAIRMENT AND COGNITIVE EVOKEDPOTENTIALS IN PATIENTS WITH PARTIAL SYMP-TOMATIC EPILEPSYA. Kostylev, and N. V. Pizova

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Clinical Hospital # 8 of Yaroslavl, Yaroslavl, RussianFederation

Purpose: Cognitive impairment among the most frequent changesaccompanying chronic epilepsy. P300 is the neuronal correlation for theattention, short term memory and decision making attitude. It is interest-ing possible relationship between neuropsychological and neurophysio-logical tests in patients with epilepsy.

Method: We investigated 37 patients (20 women and 17 men), meanage 32 € 4 years. Patients had partial symptomatic epilepsy with motorseizures and GTCS. Age of the disease was 9€ 3 years. The frequency ofseizures per month was 3 € 2. Patients were treated with standard antiepi-leptic drugs. Patients did not have depression (Tsung scale). For cognitiveauditory evoked potential we used ‘‘odd-ball’’ paradigm, the active elec-trode at the CZ, the reference electrode M1/M2. We measured the peaklatency of P300 in a superposition of two curves. For the study of cogni-tive impairment was used standart ‘‘memory for digits’’ test (memorizing12 digits in 1 minute).

Result: In patients with epilepsy found increased latency of P300 peakwith increasing age (p <0.001), as well as in healthy (‘‘aging curve’’, Pol-ish 1993). The latency of the peak for patients with epilepsy compared tothe normative data for healthy was higher, but this change was not signifi-cant. It was found that the less correct answers given during the test‘‘memory of digits’’ the higher the peak latency of P300 (P <0.005).

Conclusion: According to our data, may be a possible link neuropsycho-logical and neurophysiological changes in patients with epilepsy, but ittakes a larger sample and the control group.

p729NEUROLOGICAL AND PSYCHIATRIC ANALYSIS OFICTAL KISSING AUTOMATISME. Taskiran*, C. �zkara�, O. Kılıc�, I. Aydogdu�, A. Senturk�,and M. Ozmen�

*Istanbul University Experimental Medicine Research Institute,Istanbul, Turkey; �Istanbul University Cerrahpasa MedicalFaculty, Istanbul, Turkey; and �Ege University, Izmir, Turkey

Purpose: Automatisms are repetative motor activities that occur duringor after a seizure followed by amnesia. Several different automatismshave been described which may show complex or simple characteristicswhere ictal kissing automatism (IKA) is a very rare phenomena. Weaimed to study this complex ictal behaviour from neurological and psy-chiatric aspects in our patients and discuss including the previouslyreported cases.

Method: IKA was determined in four of our patients (3 female, 1 male)during video-EEG monitorization. Ictal EEG and video types were stud-ied in detail and all patients underwent psychiatric analyses to unveil theprobable underlying cause of kissing behaviour.

Result: Mean age of patients was 30.5 years (26–35 years). Seizuresrecorded were characterised by mainly ictal speech, kissing and gesturalautomatisms in all patients. The ladies kissed the persons close to themwhere the young man blew kisses. Seizures related to non-dominant tem-poral lobe in three (2 right, 1 left) and dominant temporal (right) in onepatient. MRI showed mesial temporal sclerosis in 3 of them where it wasnormal in one. Psychodynamic analysis revealed intense unfulfilledaffective requirements which may determine the seizure semiology andthey suffered from depression as well.

Conclusion: IK is a complex behaviour which may occur as a result ofrelease phenomena rather than a cortical stimulation related to mainlynon dominant temporal lobe and generally in women. Family dynamics,developmental history, personality, life style, feeding and love instinctsmay all play a role in the emergence of this rare automatism during a sei-zure.

p730IS PROPOFOL TOLERABLE DURING WADA?F. Alsallom, S. Sinha, S. Wahaas, A. Benito, F. Alsenani,F. Bamogaddam, and K. A. SiddiquiNational Neurosciences Institute, King Fahad Medical City,Riyadh, Saudi Arabia

Purpose: WADA test helps in pre-surgical evaluation of epilepticpatients, specifically, predicting the post surgical outcome for languageand memory. Sodium Amytal (SA) was by far the most commonly usedagent for this purpose. Lack of availability of SA had initiated the use ofPropofol (PF). We assessed the tolerability of PF for WADA testing.

Method: We retrospectively reviewed the data of 9 patients who hadWADA testing done. All had temporal lobe epilepsy (TLE) and were sur-gical candidates of temporal lobectomy. PF was utilized for WADA pro-cedure.

Result: Nine patients with mean (+SD) age 26(+5.8) years, 6 males and3 females were recruited. Six of them had left TLE, and 3 of them hadright TLE. In each patient, neurointerventionalist injected 10 mg of PF inthe Internal Carotid Artery (ICA) via a catheter inserted through a punc-ture site at the right femoral artery. Right hemispheric injection followedby left hemisphere injection after 30 minutes. During the procedure, EEGmonitoring showed changes within 5–18 seconds of injection, as hemi-spheric delta slowing, neuropsychological tests were carried out forlocalization of memory and language. We were able to lateralize speechand memory dominance in these patients. Peri-procedural complicationsincluded transient euphoria (n=1) transient spasm of internal carotidartery (n=1) and generalized tremulousness (n=2). Immediate post proce-dure there was a drop in blood pressure with average pressure of 116/66mm of Hg, in all patients, which improved after 30 minutes.

Conclusion: We found that PF is well tolerable for the WADA proce-dure, with no significant complications, although blood pressure shouldbe closely monitored

p731PERCEPTIONS OF STRESS IN LEFT TEMPORAL LOBEEPILEPSY AND DIFFERENCES IN RESPONSE TOACUTE STRESSJ. Allendorfer, H. Heyse, L. Mendoza, and J. SzaflarskiUniversity of Cincinnati Academic Health Center, Cincinnati,OH, USA

Purpose: This study examined the effects of acute stress on assessmentsof mood, anxiety and stress in left temporal lobe epilepsy (LTLE)patients.

Method: 23 LTLE patients were included; 16 believed that stressaffected their seizure control (LTLE+S) while 7 did not (LTLE–S). Alsoincluded were 17 neurologically healthy controls, stratified as high-stress(HC+S; n=9) or low-stress (HC–S; n=8). Subjects participated in a chal-lenge that induces moderate amounts of stress. Pre-challenge mood andstress/anxiety levels were assessed using the Beck Depression Inventory(BDI-II), Profile of Mood States (POMS), State-Trait Anxiety Inventory(STAI), Positive Affect (PA) and Negative Affect (NA) Schedule(PANAS), Dundee Stress State Questionnaire (DSSQ), and 10-item Per-ceived Stress Scale (PSS-10). The STAI, PANAS, DSSQ, and PSS-10were also administered post-challenge. T-tests were performed to exam-ine differences between +S and –S groups and assess pre-/post-challengeassessment changes within each of the groups (significance at p<0.05).

Result: BDI-II did not differ between +S and –S groups. LTLE+S andLTLE–S did not differ on assessments except POMS vigor-activity sub-scale (LTLE+S>LTLE-S). Compared to HC–S, HC+S scored higher onpre-challenge POMS, PSS-10, STAI, NA and DSSQ distress and loweron PA; differences remained post-challenge except DSSQ distress

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(p=0.1). LTLE+S showed pre-/post-challenge changes: decreasing PA,increasing NA, decreasing DSSQ engagement, and increasing DSSQ dis-tress. HCs also showed increasing DSSQ distress pre-/post-challenge.

Conclusion: Acute psychological stress has greater negative impact onmood and stress-related constructs in LTLE+S patients who believestress affects seizure control compared to LTLE–S and HC subjects.

p732ILLNESS PERCEPTION, QUALITY OF LIFE AND COP-ING STYLES IN PATIENTS ADMITTED TO AN EPI-LEPSY MONITORING UNITJ. A. Magee*, E. T. Burke�, N. P. Pender*, N. Delanty*, andG. M. Fortune**Beaumont Hospital, Dublin, Ireland; and �University CollegeDublin, Dublin, Ireland

Purpose: To examine the relationship between illness perception, qual-ity of life and coping styles in a sample of patients admitted to an Epi-lepsy Monitoring Unit. It was hypothesised that illness perception wouldmediate levels of distress, coping style and quality of life.

Method: This study utilises a double-blind design. Data were collectedas part of a larger ongoing prospective study of patients admitted to theEpilepsy Monitoring Unit in Beaumont Hospital. Patients completed alarge battery of self-report measures, including the Brief-Illness Percep-tion Questionnaire, Coping Inventory for Stressful Situations, MoriskeyMedication Adherence Questionnaire, Beck Anxiety and DepressionInventories and the Quality of Life in Epilepsy-13.

Result: In total, data on 65 patients with drug resistant epilepsy arereported. Analysis of preliminary data (N=25) collected so far indicatesthat illness perception impacts on level of anxiety, coping styles and hasa direct and indirect impact on quality of life. A larger regression modelwill be reported on, controlling for gender, seizure frequency and depres-sion scores in order to gain a fuller understanding of the complex rela-tionship between these variables.

Conclusion: Preliminary results indicate that illness perception plays animportant mediating role in coping styles, anxiety and quality of life. Fur-ther analyses will be conducted to examine the impact of depression scoreson illness perception, coping styles and quality of life. These findings haveimportant implications regarding the identification of individual illnessperception styles in patients with epilepsy and the impact of this uponpatients’ management of their epilepsy and psychological well-being.

p733DO BRAIN LESIONS INCREASE THE RISK OF DEPRES-SION IN EPILEPSY?N. Cinar, S. Sahin, T. O. Onay, K. Batum, and S. KarsidagMaltepe University, Faculty of Medicine, Istanbul, Turkey

Purpose: Psychiatric disorders are observed more frequently in patientswith epilepsy and may cause an important impact on quality of life. Inthis study, we have investigated the relationship between depression andbrain lesions in epileptic patients.

Method: Epileptic patients who had complete radiologic and neuro-physiological data were enrolled to the study. Epileptic seizures wereclassified according to the International League Against Epilepsy (ILAE)classification of epileptic seizures (1981) and psychiatric diagnoses werecategorized according to Diagnostic and Statistical Manual of MentalDisorders, Fourth Edition (DSM-IV). The presence of brain lesions werecompared in epileptic patients with or without depression.

Result: One hundred eighty epileptic patients were enrolled to the study.Forty patients were excluded who had non-depressive psychiatric disor-

ders. Depression was detected in 31 patients (21 female, 10 male) of 140patients. Thirty-two percent of patients with depression had partial, 68%had generalized seizures. Among patients without psychiatric disorder(60 female, 49 male), 29% had partial, 71% had generalized seizures.There were significant differences in age and the presence of cerebrallesion between patients with depression and patients without psychiatricdisorder. The mean age was 42€19 years and the rate of cerebral lesionswas 42% in patients with depression. The mean age was 32€19 years andthe rate of cerebral lesions was 22% in patients without psychiatric disor-der. There were no significant differences in gender, family history, thehistory of febrile convulsions, seizure frequency and the type of antiepi-leptic medication.

Conclusion: The psychiatric aspects of epilepsy are affected by manyfactors, including the epileptogenic location and nature of the underlyinglesion. Studies have shown up to a 11–60% incidence of depression inepilepsy. Depression ratio was found as 17% in our study. Our resultsalso suggests that the lesion ratio is nearly two-fold higher in patientswith depression in epilepsy. Further investigations are needed.

p734FEAR-SPECIFIC MODULATION OF TACTILE PER-CEPTION IS DISRUPTED AFTER AMYGDALALESIONSC. Bertini*, C. Passamonti�, C. Scarpazza*, N. Zamponi�,L. Provinciali§, and E. L davas**University of Bologna, Cesena, Italy; �Ospedali Riuniti-Ancona, Ancona, Italy; �Ospedali Riuniti-Salesi, Ancona, Italy;and §Universit Politecnica delle Marche, Ancona, Italy

Purpose: The perception of tactile stimuli on the face is modulated whensubjects concurrently observe a face being touched; this effect is termed‘‘Visual Remapping of Touch’’, or the VRT effect, and might represent avisually evoked somatosensory activity. VRT effect is modulated by spe-cific key information processed in face-to-face interactions: facial emo-tional expression. Indeed, tactile perception in healthy subjects isenhanced when viewing touch towards a fearful face compared to viewingtouch towards neutral, happy or angry expressions. The fear-specific mod-ulation of the VRT effect might be interpreted as an adaptive preferentialenhancement of the somatosensory cortices in presence of fearful stimuli.The present experiment was designed to test whether the amygdala, a cru-cial neural site in fear perception, might contribute to this effect.

Method: Six epileptic patients (mean age: 20 years) with lesions to theamygdala due to temporal lobe resection received tactile stimuli near theperceptual threshold, either on their right, left or both cheeks. Concur-rently, they watched several blocks of movies depicting a face with a neu-tral, happy or fearful expression that was touched or just approached byhuman fingers. Participants were asked to distinguish between felt unilat-eral and bilateral tactile stimulation.

Result: Tactile perception was enhanced when viewing touch onlytowards a neutral face, while no effect was found when patients viewedtouch towards fearful or happy faces.

Conclusion: Results of the present experiment suggest that the amyg-dala modulates the activity of the somatosensory cortices, playing a cru-cial role in mediating the fear-specific enhancement in the VRT effect.

p735FACIAL IDENTITY AND EMOTION RECOGNITION INPATIENTS WITH MESIAL TEMPORAL LOBE EPI-LEPSYA. Gomez-IbaÇez*, E. Urrestarazu*, G. Arrondo�, M. A. Pastor*,and C. Viteri**Clinica Universidad de Navarra, Pamplona, Spain; and�Center for Applied Medical Research, Pamplona, Spain

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Purpose: To evaluate facial identity and emotion recognition in patientswith mesial temporal lobe epilepsy due to amygdalo-hippocampal sclero-sis (MTLE-AHS).

Method: We studied patients diagnosed with MTLE-AHS, idiopathicgeneralized epilepsy (IGE) and healthy controls. Baseline cognitive func-tion was assessed through neuropsychological tests. Identity recognitionwas evaluated with computerized Benton Facial Recognition Test(BFRT) and recognition of basic emotions (anger, disgust, fear, happi-ness, sadness and surprise) with Ekman & Friesen test (E&FT). Time gapbetween presentation of emotion and response was measured.

Result: Seven MTLE-AHS, 10 IGE patients and 20 healthy controlswere analyzed. Median age was 35.6, 30.7 and 37.9 years respectively.Trail-Making-part B, Digit Span and word fluency tasks were signifi-cantly impaired in MTLE-AHS patients (p<0.05). MTLE-AHS patientsscored lower than controls in BFRT (36.4 vs 41.9), but slightly higherthan IGE individuals (36.4 vs 35.8; n.s.). MTLE-AHS subjects scoredlower in E&FT (40.7) than IGE (42.9) and healthy controls (49.5;p<0.05). ‘‘Happiness’’ was the easiest emotion to recognize; ‘‘fear’’ themost difficult, especially for MTLE-AHS patients (35.7% of success) vscontrols (62.5%). Recognition time was globally longer in wrong than incorrect responses (4.7 vs 3 seconds). The longest difference was observedin MTLE-AHS individuals (5.8 vs 3.4 seconds); generally, MTLE-AHSanswers delayed more than IGE or healthy subjects.

Conclusion: MTLE-AHS patients seem to have a facial emotion recog-nition impairment, especially ‘‘fear’’, with longer response time. Milddifficulty in identity recognition was also pointed. Mechanisms involvedin emotion recognition failure could be investigated with other tech-niques such as fMRI or eye-tracking.

p736NEUROPSYCHOLOGICAL OUTCOMES IN ADULTSWITH TUBEROUS SCLEROSIS COMPLEXA. Vignoli*, K. Turner*, F. La Briola*, A. Piazzini*,E. Zambrelli*, V. Chiesa*, G. Scornavacca*, R. M. Alfano�, andM. P. Canevini**St Paolo Hospital, Milan, Italy; and �Department of MolecularBiology, Milan, Italy

Purpose: Tuberous sclerosis complex (TSC) is an autosomal-dominantgenetic disorder and is a frequent cause of epilepsy and different degreesof neuropsychological impairements. The goal of this study was to assesscognitive outcome in patients with TSC and identify specific clinicalvariables correlated to neuropsychological profiles.

Method: Out of 119 adult patients currently followed at Neurology II-Epilepsy Center, St Paolo Hospital in Milan, 84 individuals underwent toa complete neuropsychological evaluation. This battery included the fol-lowing cognitive functions: intelligence, memory, attention, languageand executive functions. Subjects were divided into three groups (normalcognition, mild delay, moderate-severe delay) according to resultsobtained from cognitive evaluation.

Result: Of 84 enrolled patients (56 F, 28 M, mean age = 34.0), therewere 31 (37%) subjects with normal cognition, 21 (25%) with mild delayand 32 (38%) with moderate-severe delay. 72 subjects (85%) had epi-lepsy, with mean age at onset of seizures of 3.9 years (ranged from 1month to 48 years). 33 (46%) had a history of infantile spasms and 34(47%) presented refractory epilepsy. 17 (20%) patients were diagnosedwith TSC1 mutation, 49 (58%) with TSC2, 9 (11%) with no mutation and9 (11%) are ongoing. Cognitive outcomes were correlated with age ofepilepsy onset, history of infantile spasms, genetic analysis, refractoryepilepsy and seizure frequency (p<0.05).

Conclusion: Our data suggest that, in patients with TSC, the age at onsetof epilepsy, history of infantile spams, seizure frequency and geneticmutation are predictive of cognitive function.

p737QUANTITATIVE METHOD FOR IDENTIFICATION OFTHE LANGUAGE ELOQUENT AREAS DURING PRE-SURGICAL SEEG RECORDINGSC. Pastori*, V. Gnatkovsky*, S. Francione�, F. Pelle�,L. Castana�, and M. De Curtis**Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan,Italy; �Ospedale Niguarda C Granda, Milan, Italy; and�Niguarda General Hospital, Milano, Italy

Purpose: A definition of eloquent areas of the brain in drug resistant epi-lepsy patients explored by stereo-EEG is fundamental for defining theboundaries of the resection. These patients may present peculiar and sub-verted anatomy. The development of quantitative method for identifyingtask-related anatomical areas while performing neuropsychological testduring the recording sessions, could help in surgical decision.

Method: A new software (Elpho-SEEGª) for computerized stereo-EEG signals analysis was developed to compare brain activity duringneuropsychological tests and control condition. Fluency tasks (phone-mic- semantic) were analyzed in 11 right-handed patients explored indominant frontal lobes. Identified anatomic areas were correlated withelectrophysiological stimulation responses during SEEG recordings. Aco-localization of activated contacts was performed with MRI data.

Result: Different frequencies and the relative power evaluated by Fou-rier transformation and further integral algorithms were analyzed in allrecording leads. Difference in the power of frequencies between controlconditions (quiet awake, Benton test) and fluency tasks was identified. Inall the cases, frequency changes in brain structures involved in languagenetwork was observed. The frequency changes were patient specific andnot task or structure specific. These areas often corresponded to struc-tures where electrical stimulations induce language disturbances. Testactivated contacts were visualised on MRI.

Conclusion: Fluency task frequency changes defined by our quantita-tive analysis can be used to identify language structures explored byintracranial electrode. Validation of our method on larger group ofpatients is necessary to apply it in surgical planning, outcome predictionand investigation of other cognitive networks. Supported by Italian Min-istry of Health Young Investigator Grant 2007.


p738LONG-TERM EVOLUTION OF DIFFERENT NEURO-PSYCHOLOGICAL PHENOTYPES IN SCN1A SPEC-TRUMC. Passamonti*, C. Petrelli�, L. Provinciali�, and N. Zamponi�

*Ospedali Riuniti-Ancona, Ancona, Italy; �Universit Politecnica delle Marche, Ancona, Italy; and �Ospedali Riuniti-Salesi, Ancona, Italy

Purpose: Mutations of SCN1A-gene cause epilepsy syndromes of vari-able severity, from familial febrile seizures (FS) to partial Epilepsy withFebrile seizure plus (PEFS+), Generalized Epilepsy with Febrile seizureplus (GEFS+), and finally Dravet Syndrome, along with its mild variant(Catterall et al, 2010). These different clinical phenotypes are character-ized by widely variable cognitive and behavioural profiles. The presentstudy was aimed to investigate the long term neuropsychological evolu-tion of epileptic patients carrying a SCN1A-gene mutation.

Method: Twenty subjects with recurrent febrile and afebrile seizures inthe first two years of life and confirmed SCN1A-gene mutation were

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studied both prospectively and retrospectively. Clinical data and formalneuropsychological assessments including cognitive level, language,executive functions, visuo-motor functions and behaviour were availablesince epilepsy onset to the late adolescence.

Result: Patients diagnosed as Dravet showed the lowest cognitive levelat epilepsy onset and the worst clinical and neuropsychological evolu-tion, especially those who experienced status epilepticus in childhood.Autistic symptoms and hyperactivity were present in most of thesepatients. Patients with the mild variant showed a borderline cognitivelevel, a greater impairment in visuo-motor than linguistic functions, andemotional disturbances until adolescence. GEFS+ patients showed nor-mal cognitive functioning but a delay in language acquisition and impair-ments in visuo-motor functions, which progressively improved after 6years of age. No cognitive and behavioural problems were detected inPEPS+ patients.

Conclusion: SCN1A-gene mutations are associated to different neuro-psychological profiles, characterized by language impairments and com-mon difficulties in visuo-motor functions. Clinical variables linked toepilepsy's severity modulate the neuropsychological evolution.

p739STEREOTACTIC RADIOFREQUENCY AMYGDALO-HIPPOCAMPECTOMY FOR THE TREATMENT OFTEMPORAL LOBE EPILEPSY: DO GOOD NEUROPSY-CHOLOGICAL AND SEIZURE OUTCOMES CORRE-LATE WITH HIPPOCAMPAL VOLUME REDUCTION?H. Malikova, L. Kramska, R. Liscak, Z. Vojtech, andT. ProchazkaNa Homolce Hospital, Prague, Czech Republic

Purpose: Temporal lobe surgery bears the risk of a decline of neuropsy-chological functions. Stereotactic radiofrequency amygdalohippocamp-ectomy (SAHE) represents an alternative to mesial temporal lobeepilepsy (MTLE) surgery. This study compared neuropsychologicalresults with MRI volumetry of the residual hippocampus.

Method: We included 35 patients with drug-resistant MTLE treated bySAHE. MRI volumetry and neuropsychological examinations were per-formed before and 1 year after SAHE. Each year after SAHE clinical sei-zure outcome was assessed.

Result: One year after SAHE 77% of patients were assessed as Engel¢sClass I, 14% of patients was classified as Engel¢s II and in 9% of patientstreatment failed. Two years after SAHE 76% of subjects were classifiedas Engel¢s Class I, 15% of patients was assessed as Engel¢s II and in 9%of patients treatment failed. The hippocampal volume reduction was58€17% on the left and 54€27% on the right side. One year after SAHEthe intelligence quotients of treated patients increased. Patients showedslightly significant improvement in verbal memory (p=0.039) andsemantic long-term memory subtest (LTM) (p=0.003). Patients treatedon the right side improved in verbal memory, delayed recall and LTM.No changes in memory were found in patients treated on the left side.There was a trend between the larger extent of the hippocampus reductionand the improvement in visual memory in speech-side operated(p=0.057). No other relationships between the hippocampal reductionand clinical outcome were significant.

Conclusion: SAHE causes partial hippocampal destruction, but seizureoutcome is comparable with open surgery and moreover SAHE does notcause neuropsychological deficits.

p740MONTREAL COGNITIVE ASSESSMENT PERFOR-MANCE IN PATIENTS WITH EPILEPSYJ. Ding, L. Mao, and X. WangZhongshan Hospital, Fudan University, Shanghai, China

Purpose: To compare the screening abilities of montreal cognitveassessment (MoCA) and mini–mental state examination (MMSE) indetecting cognitive impairments in idiopathic epilepsy patients.

Method: Scores on the MoCA and the mini-mental state examination(MMSE) were compared in 100 patients with idiopathic or probablesymptomatic epilepsy and 30 age- sex- edu-matched controls. As previ-ously recommended, a MoCA score less than 26 was used to indicate thepresence of at least mild cognitive impairment (MCI).

Results: Epilepsy patients exhibited significantly decreased MoCAscores compared to controls, whereas MMSE scores showed no differ-ence between two groups. The percentage of epliepsy patients scoringbelow a cutoff of 26/30 was higher on the MoCA than on the MMSE.31.03% of patients with normal MMSE scores had cognitive impairmentaccording to their MoCA score. Impairments were seen in several cogni-tive domains, includingvisuospatial and executive abilities, attention,memory, and language.

Conclusion: Compared to MMSE, the MoCA may be a more sensitivetool to identify varies cognitive impairments in epilepsy patients.

p741CHANGES IN NEUROCOGNITION AND QUALITY OFLIFE AFTER BILATERAL ELECTRICAL STIMULA-TION OF THE ANTERIOR THALAMIC NUCLEI IN 7PATIENTS WITH REFRACTORY EPILEPSYM. Milian*, I. Wisniewski�, A. Wendling�, S. Klamer*,A. Gharabaghi*, and S. Rona**University Hospital Tuebingen, T�bingen, Germany; and�Epilepsy Center, Kehl-Kork, Germany

Purpose: The SANTE study reported memory problems and depressionas adverse events of deep brain stimulation (DBS) of the anterior thalamicnuclei (ATN). We assessed changes in neurocognition and quality of life(QoL) after bilateral DBS of the ATN in patients with refractory epilepsy.

Method: Seven adult epilepsy patients (4 female, 3 male) underwentcomprehensive neuropsychological testing and completed QoL and psy-chiatric inventories before DBS surgery. Three patients were re-evalu-ated 4 weeks after implantation of electrodes, but before onset ofstimulation, all 7 patients after 4 months of stimulation, and one patientafter an additional 4 months of unilateral (right) stimulation.

Result: One month after implantation, before turning on the stimulator,we observed only a slight decline in verbal long-term memory, butimprovement of depression and QoL scores. Four months after stimula-tion onset we noticed a significant decrease in nonverbal short-termmemory and a tendency towards verbal and nonverbal long-term memorydecline. There were no changes in general cognitive abilities (IQ), atten-tion, executive and language functions or visuospatial abilities. Mood,QoL and psychiatric profile also remained unchanged. In one patientwhere left-sided stimulation was turned off due to a decline in verbalmemory, we observed a recovery 4 months after deactivation.

Conclusion: In the present sample we demonstrated (reversible) verbaland nonverbal memory changes as a medium-term effect of DBS of theATN in epilepsy patients. Stimulation affected no other cognitive func-tions, mood, QoL or psychiatric scales. Further investigations are sched-uled in a larger group of patients.

p742ACCELERATED LONG-TERM FORGETTING, SUBJEC-TIVE MEMORY COMPLAINTS AND DEPRESSION INMEDIAL TEMPORAL LOBE EPILEPSYS. Yagci*, M. Uzan*, L. Hanoglu�, and C. �zkara**Cerrahpasa Medical Faculty, Istanbul University, Istanbul,Turkey; and �Istanbul Medipol University, Istanbul, Turkey

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Purpose: Patients with medial temporal lobe epilepsy (MTLE) oftenpresent with memory complaints despite performing within normal limitson standard memory tests over usual delays (30 minutes). More recentlyMTLE has been associated with the phenomenon of accelerated long-term forgetting (ALF). This study aim to investigate ALF phenomenonand its relationship with subjective memory complaints and depression inMTLE patients.

Method: Twenty-six patients with MTLE and 23 healthy controls weregiven California Verbal Learning Test (CVLT), Subjective MemoryComplaints and Beck Depression Inventory. Participants were tested onCVLT for learning, immediate recall and recognition at 30 min, 1 week,6 week intervals. Accelerated forgetting rate was calculated by decay ofrecognition scores

Result: In contrast to patients with right MTLE and control group, leftMTLE patients showed significantly poorer performance on learning tri-als and greater ALF on 30 minutes recognition. At the first and 6 weekrecognition, both groups of patients demonstrated close forgetting ratesunlike controls. On the measure of accelerated forgetting, both patientgroup showed significant ALF comparison to control group. Betweenfirst and 6 week interval, either right and left MTLE patients demon-strated faster decay of forgetting. Also depression and subjective memorycomplaints trend towards greater at left MTLE patients but did not differin right MTLE and controls. Although depression were not found associ-ated with ALF, decay of immediate and 30 minutes recall negatively cor-related with depression scores in all groups.

Conclusion: The findings provide evidence consistent with the periodof consolidation for verbal memory can be disrupted by both left andright MTLE. Patients with left MTLE show slightly significant acceler-ated long-term fogetting and trend towards greater depression.

p743NEUROPSYCHOLOGICAL OUTCOME AFTER EPI-LEPSY SURGERY IN PATIENTS WITH BILATERALAMMON'S HORN SCLEROSISV. L. Vogt*, M. P. Malter*, J. Schoene-Bake*, C. G. Bien�,M. Von Lehe*, H. Urbach*, J. Witt*, and C. Helmstaedter**University of Bonn, Bonn, Germany; and �Krankenhaus Mara,Bielefeld, Germany

Purpose: To retrospectively evaluate the risks versus benefits of epi-lepsy surgery in patients with bilateral ammon's horn sclerosis (bAHS)regarding cognition, mood, and quality of life.

Method: Neuropsychological outcome of eleven surgically and eightmedically treated patients with bAHS was evaluated. Memory (verbal/figural) and executive functions (fluency, response inhibition) wereassessed in terms of individual scores and a composite memory or atten-tion scores. Additionally, mood and quality of life were evaluated.

Result: Within the observation interval, 91% of the surgical but no medi-cal patients achieved seizure freedom. Executive functions did not changein either group. Despite severe memory deficits already at baseline, thesurgical group significantly declined in the composite memory (z=-2,401,p=.016). Reliable change indices (CI = .90) revealed that while 27% of thesurgical group declined in the composite memory score, no patientsimproved (individual scores: 73% decline and 9% improvement in verbalmemory; no change in nonverbal memory). In the control group, nodeclines of the composite memory score were evident (individual scores:25% decline in verbal memory, 13% decline in nonverbal memory). Atfollow up, the groups did neither differ with respect to subjective memoryimpairment in everyday life nor in regard to mood or quality of life.

Conclusion: Our findings suggest that despite undeniable benefits con-cerning seizure control and very poor memory already at baseline,patients with bAHS still show additional postoperative memory decline.This and the lack of benefits regarding subjective cognition, mood andquality of life put the overall outcome in perspective.

p744APPLICABILITY OF A MEMORY ASSOCIATION TASKFOR FMRI IN EPILEPSY SURGERYN. L. Frankenmolen*, M. Hendriks�, H. Bergmann�,A. Aldenkamp�, P. Hofman§, R. Kessels�, and P. Ossenblok–

*Radboud University Nijmegen, Nijmegen, The Netherlands;�Epilepsy Centre Kempenhaeghe, Heeze, The Netherlands;�Radboud University Nijmegen, Nijmegen, The Netherlands;§Kempenhaeghe, Heeze, The Netherlands; and –Heeze, TheNetherlands

Purpose: Epilepsy patients undergoing neurosurgery are at risk for post-operative language and memory deficits. To minimize this risk it isimportant to assess brain regions for language and memory preopera-tively, using a non-invasive method such as fMRI. For language laterali-zation this has been successful. However, no sensitive fMRI memorytask is currently available for this purpose. The objective of this study isto develop and examine a sensitive fMRI memory task (face-name-asso-ciation memory) that provokes bilateral hippocampal activation inhealthy volunteers.

Method: Ten healthy adults participated in the study (6 females, meanage 36.7, sd 18.2). The participants encoded the faces and names in thescanner, while functional images were obtained. A recognition task wasperformed afterwards. Results from the random effects analyses werefirst thresholded at p< 0.001 (uncorrected). Subsequently, an anatomicalregion of interest (ROI) of the hippocampas was used to mask for small-volume corrections (tested at pFDR < 0.05).

Results: Showed significant hippocampal activations in 9 out of 10 par-ticipants. The ROI analysis showed bilateral hippocampal activations in8 participants and unilateral hippocampal activations in one participant.In one participant no task-specific hippocampal activation could be deter-mined. The mean recognition score across all participants was 75%(M=36.3/48, sd=5.6).

Conclusion: The present study shows that this face-name-associationtask is a useful fMRI memory task that provokes bilateral hippocampalactivations in individual participants. This may be a suitable task for clin-ical purposes. Further research will focus on validating this task in thepreoperative memory assessment of epilepsy surgery candidates.

p745LANGUAGE AFTER TEMPORAL LOBE EPILEPSYSURGERYA. R. Giovagnoli, V. Manfredi, A. Parente, S. Oliveri, G. Didato,F. Deleo, L. D’Incerti, C. Marras, F. Villani, and R. SpreaficoFondazione IRCCS Istituto Neurologico C. Besta, Milano, Italy

Purpose: Language competence depend on the integrity of differentneural networks including the inferior-lateral temporal, superior parie-tal and frontal cortices, and the ventral visual pathway or the inferiorfrontal, dorsolateral prefrontal, medial temporal and parietal areas.Although many studies investigated language after epilepsy surgery,scarce attention was given to the postoperative trajectories of differentlexical-semantic abilities. This prospective study evaluated the shortand long-term changes of word finding on visual, letter, and categorystimuli in patients operated on for drug-resistant temporal lobe epi-lepsy (TLE).

Method: Eighty-eight adult patients with left or right TLE were evalu-ated before and six months and one, two, three, and four years after sur-gery. The surgical resections involved, to different extent, the anteriorlateral and medial temporal lobe structures. The Boston Naming andWord Fluency tests on phonemic and semantic cues were used to assessword finding on visual (line-drawing) stimuli, search by letter, or cate-gory access to the lexical store.

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Result: All patients reported complete seizure remission except for 14cases with sporadic attacks. With respect to the preoperative evaluation,at the 6-month follow-up, the naming test scores were significantly lowerin the left TLE patients and higher in the right TLE patients, but, at the 1-year, 2-year, 3-year and 4-year follow-ups, naming improved in bothgroups. In left and right TLE, word fluency on phonemic or semantic cuesprogressively increased after surgery.

Conclusion: Word-finding abilities tend to improve 1–4 years after leftor right TLE surgery, showing different trajectories. Early impairmentand subsequent improvement of picture naming strictly relate to leftTLE, whereas word finding by letter or category improves irrespectivelyfrom the side of surgery. These results indicate that, in selected patients,language can continue to ameliorate for long time after surgery. Ongoingliberation of anterior and posterior cortical areas from the interference ofepileptic discharges may explain language recovery.

p746TEMPORAL LOBE EPILEPSY IMPAIRS ADVANCEDCOGNITIVE ESTIMATION ABILITIESA. Parente*, A. Tarallo*, F. Villani�, R. Spreafico�, andA. R. Giovagnoli**Fondazione IRCCS Istituto Neurologico C. Besta, Milano,Italy; and �Fondazione IRCCS Istituto C. Besta, Milano, Milano

Purpose: Cognitive estimation, an ability to attribute measurements toconcrete things, stands on individual semantic knowledge and experi-ences, contributing to everyday decision making and behaviour. Tempo-ral lobe epilepsy (TLE) is a well-known cause of memory deficits butother cognitive impairments may be observed in patients with medicallyintractable seizures, playing an important role in localizing the epilepsyrelated dysfunction. The aim of this study was to determine cognitiveestimation deficits in TLE patients, candidates to epilepsy surgery.

Method: One hundred and eight e TLE patients and 51 healthy subjectswere evaluated. The Cognitive Estimation Task (CET) requiring simpleand complex estimations and tests assessing executive, attentive, percep-tual, praxis, language, and memory functions were used.

Result: Both left and right TLE patients showed significantly lowerCET scores than controls. In the whole patient group, the CET scores cor-related with executive and language test scores, the age at seizure onset,and epilepsy duration.

Conclusion: TLE impairs cognitive estimation, which may reflect theseverity of disease and the involvement of other cognitive abilities. Suchimpairment may depend on damage to the temporal lobes. Alternatively,through pre-existing neuron pathways, long-lasting TLE may interferewith functions supported by distant brain areas that play a role in controlfunctions (e.g., the frontal lobes). As an important cognitive dimension,cognitive estimation deserves attention in drug-resistant TLE patients.Further studies in larger patient populations are needed to confirm theseexploratory findings, while longitudinal postoperative studies could helpclarify the physiopathological mechanisms of cognitive estimation.

p747THE DMS-48 AS A VISUAL RECOGNITION MEMORYTASK FOR COGNITIVE EPILEPSY EVALUATIONI. Wisniewski*, A. Wendling*, C. Westermann*, L. Manning�,and B. J. Steinhoff**Kork Epilepsy Centre, Kork, Germany; and �Laboratory ofImaging and Cognitive Neurosciences (CNRS, UMR 7237, IFR037), Strasbourg, France

Purpose: Currently no consensus exists regarding the lateralizing valid-ity of established visual memory tests in pre-surgical epilepsy diagnos-

tics. The Delayed Matching to Sample (DMS-48) task was previouslyshown to successfully assess visual recognition memory deficits in earlyAlzheimer Disease, thus we determined that this task was applicable forlateralisation of hippocampal regions and parallel versions for evaluationof postoperative memory outcome.

Method: Forty-eight preoperative mesial temporal lobe epilepsy(TLE) patients were given a full neuropsychological battery containinga variety of standard verbal and figural learning and reproductionmemory tests, in addition to the DMS-48. Furthermore, to eliminatepractice effects post-operatively, two parallel versions of the DMS-48were developed and normalised in 172 healthy controls. Using theseparallel versions allowed a group of TLE patients to be assessed post-operatively.

Result: Our analysis revealed highly significant differences between theleft and right mesial temporal lobe for both the DMS-48 and the parallelversions, but not for any of the other visual memory tasks we studied.The two parallel versions administered to the control group were found tobe comparable tools to the original task, and could thus be utilized for thepostoperative follow up. Postoperatively, all visual memory measuresremained stable, while performance on verbal memory tasks diminishedin the left TLE patients.

Conclusion: The present findings suggest that clinical usefulness is highfor both the DMS-48 and its parallel versions for pre- and postsurgicalcognitive epilepsy evaluation, by lateralising the ictal onset zone andcontrolling postoperative changes.


p748EPILEPSY CHILDREN SUPPORT CAMPL. Cvitanovic-Sojat, B. Divcic, R. Gjergja Juraski, M. Malenica,M. Kukuruzovic, N. Rajacic, and N. KrmekUHC Sestre milosrdnice, Zagreb, Croatia

Purpose: To analyze the benefits of a week long summer camp orga-nized by the Croatian Biro for Epilepsy and supported by the City Officeof Zagreb for Health and War Veterans.

Method: A summer camp was established for children with epilepsy ofnormal intellect and with well-controlled seizures on anti-epileptic medi-cation. Camp staff included doctors, psychologist, nurses and trained vol-unteers. Activities included swimming, group sports, arts and crafts,wildlife exploration and entertainment. Eight education sessions wereprovided by psychologists/neuropaediatricians and were centered onimproving knowledge of seizures, the importance of medication and onmanaging lifestyle issues such as employment and driving. Discussionwith camp participants occurred in groups or in one-on-one sessions. Theimpact of the educational sessions was evaluated at the beginning and atthe end of the camp. Questionnaires explored stressors and methods ofrelaxation, bullying, concentration, knowledge about epilepsy and satis-faction with the camp.

Result: A total of 20 children attended the camp, (males =10, age range8 to 18 years, mean age 13 years and 11 months). The analyses showedthat 15/20 children were aware that they had a diagnosis of epilepsy, butthat none knew what epilepsy was. Only parents knew the diagnosis in 2/20. One child had a generalized seizure and one child had an absence sei-zure during the camp.

Conclusion: All participants were encouraged to reach their full poten-tial in life and to improve their knowledge of epilepsy and associated life-style modifications to ensure good health. Participants enjoyed theexperience and received education in a supportive environment.

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p749INFLAMMATORY TEMPORAL LOBE EPILEPSY:FOCAL RASMUSSEN ENCEPHALITIS?L. De Palma*, C. Sabourdy�, L. Minotti�, S. Chabardes�, andP. Kahane�

*Neurology Department, University Hospital, Grenoble,France, Grenoble, France; and �Grenoble University Hospital,Grenoble, France

Purpose: Rasmussen encephalitis is a well-known form of focal epi-lepsy associated with brain unilateral atrophy and hemiparesis. It is pos-tulated that some patients, more often adults, could present, at thebeginning, a more focal disease that involves later the entire hemisphere.It is still unclear if focal forms of Rasmussen encephalitis do exist.

Method: We report the case of a twelve years old girl with normaldevelopment who started her epilepsy at the age of 10 years. The seizureswere, from the beginning, very frequent and stereotyped. They were char-acterised by an abdominal aura (painful), followed by gustatory andolfactory hallucinations, with inconstant dizziness. The girl didn't haveany speech and consciousness impairment. Inter-ictal and ictal EEGabnormalities were localised on the anterior temporo–basal region. MRIshowed an ill-defined lesion of the amygdala, hyperintense in T2, hypo-intense in T1, visible in diffusion. CSF analysis was normal, with no anti-NMDA and anti-VGKC antibody. The epilepsy was drug resistant fromthe onset, with clear anatomo-electro-clinical correlations.

Result: A temporo-polar resection including the hippocampus was thenperformed without neither memory nor speech deficit after surgery.

The patient, 10 months after the intervention, is in Engel class 1a.Neuropathological examination showed a perivascular inflammationmainly of type T lymphocyte (CD8/CD4 >1) in the amygdale, withoutany structural alterations, suggesting a focal form of Rasmussen encepha-litis. No additional treatment was proposed.

Conclusion: This report enlarges the spectrum of clinical manifestationsof Rasmussen encephalitis where very focal forms seem to exist, even inchildren.

p750A NOVEL INTERNET ANIMATION SEIZURE SURVEYMAY BE AN EFFECTIVE SCREENING INSTRUMENTFOR POPULATION-BASED RESEARCHW. J. D’Souza, J. Freeman, S. Harvey, and M. CookThe University of Melbourne, Melbourne, Vic., Australia

Purpose: The conventional research method to screen for epilepsy iswith a written questionnaire administered door-to-door (WQ). Althoughthis enables comprehensive capture of undiagnosed and untreated cases,it is resource intense, insensitive to non-convulsive seizures and ineffi-cient for large-scale recruitment for aetiologic or prognostic studies. Ouraim was to ‘field test’ a novel digital animation seizure-screening ques-tionnaire that may be more suitable for community-based recruitment.

Method: We developed a series of high-resolution digital animationsdepicting visual sequences of young people with seizures (AQ) consist-ing of: tonic-clonic, simple partial motor, complex partial temporal lobe,absence and myoclonic. We administered AQ to parents of primary andsecondary school students and secondary school students by a speciallyconstructed website www.sparks.org.au. All students underwent epilepsyspecialist assessment (ESA) including EEG when indicated, to confirmthe diagnosis. AQ was repeated after first completion, to estimate repeat-ability.

Result: 206 AQ internet surveys were conducted (157 parental, 38 stu-dents with all undergoing ESA: 8 screened positive with 3 confirmed epi-leptic seizures, 2 of which were new. Both parental and student's surveyscombined: sensitivity 1.00 (1.00–1.00), specificity 0.95 (0.92–0.99),

Youden's Index – a summary measure of sensitivity and specificity - 0.95(0.93–0.99). Surveying only parents improved specificity slightly with-out affecting sensitivity. Repeat survey (n=62) demonstrated 100% con-cordance.

Conclusion: Although numbers are relatively small, early results sug-gest that AQ may be a more effective population-screening instrumentthan WQ. In addition, it should greatly improve efficiency as it can read-ily access individuals and households through devices that access the in-ternet, rather than door-to-door.

p751THE INFLUENCE OF ANTIEPILEPTIC DRUG THER-APY ON BONE MINERAL DENSITY AND SERUMTOTAL AND IONIZED CALCIUM LEVELS IN CHIL-DREN AND ADOLESCENTSM. D. Dimic*, and N. A. Dimic�

*Clinical Center NiÐ, Serbia, Nis, Serbia; and �Institut NiskaBanja, Niska Banja, Serbia

Purpose: Longterm use of antiepileptic drugs (AED) in patients withepilepsy can produce a reductions of bone mineral density (BMD). Theaim of this study is to evaluate the influence of antiepileptic drugs onbone and calcium metabolism in children and adolescents with epilepsy.

Method: We prospectively measured the spinal BMD by dual-energyH-ray absorptiometry and serum total and ionized calcium values in 31male patients aged 6–18 years who received AED mono and polytherapy.

Result: Despite of BMD apsolute values in lumbar spine region (L1-L4)were significantly decreased (0.830€0.14 g/cm2 vs. 0.908€0.18 g/cm2;p<0.05), BMD Z-scores (-0.18€1.47 vs. 0.23€0.68; n.s.) were not signifi-cantly lower in epilepsy patients group compared with control. The serumtotal and ionized calcium values were significantly lower in male patientswith epilepsy compared to control (total calcium levels: 2.30€0.18mmol/L vs. 2.45€0.13 mmol/L p<0.001 and ionized calcium levels1.15€0.14 mmol/L vs. 1.23€0.05 mmol/L p<0.005).

Conclusion: Because longterm AED-therapy can produce disturbancesin bone mineral metabolism in children and adolescents with epilepsy,both management and calcium and vitamin-D suplementation are neces-sary.

p752IMPORTANCE OF SUBTLE CLINICAL FEATURESASSOCIATED TO THE MOTOR PHENOMENON OFEPILEPTIC SPASMS FOR DIFFERENTIAL DIAGNOSISM. Eisermann*, P. Plouin*, O. Dulac�, R. Nabbout�, andA. Kaminska�

*Necker Enfants Malades Hospital, Paris, France; and �HopitalNecker Enfants Malades, Paris, France

Purpose: Epileptic spasms are a peculiar seizure type occurringthroughout life, in the neonatal period in Othahara syndrome, in infancyin West syndrome, in childhood in late onset epileptic spasms and possi-bly in Lennox Gastaut syndrome, and in later life in focal symptomaticepilepsies due to focal cortical malformations. The typical clinical mani-festation consists in a sudden motor phenomena, longer compared to amyoclonus but shorter compared to a tonic seizure, of variable characterand localisation, possibly asymmetrical and/or asynchronous, and mostoften occurring in clusters. Associated features may occur but can be verysubtle and therefore easily be overlooked, but their detection can be veryimportant in the work-up of the underlying etiology.

Method: We present the ictal video-EEG recordings and clinical data ofpatients with epileptic spasms showing a variety of associated features

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beside the motor phenomenon, as behavioral arrest, decreased respon-siveness, chewing, different ocular phenomena and autonomic changesas larming, vomiting, and short lasting cardiac rhythm changes.

Result: We present the ictal video-EEG recordings and clinical dataof patients with epileptic spasms showing a variety of associated fea-tures beside the motor phenomenon, as behavioral arrest, decreasedresponsiveness, chewing, different ocular phenomena and autonomicchanges as larming, vomiting, and short lasting cardiac rhythmchanges.

Conclusion: Detection and characterization of subtle clinical featuresassociated to the motor phenomenon of epileptic spasms are important toguide the differential diagnosis.

p753SCHOOL YEARS FOR CHILDREN WITH EPILEPSY INGREECE: A VOICE COMING FROM PARENTS ANDCHILDRENM. Kampra*, A. Siatouni�, A. Verentzioti�, N. Tzerakis�,G. Androutsos*, E. Katsarou§, and S. Gatzonis�

*Medical School of Athens, Athens, Greece; �Athens MedicalSchool, Athens, Greece; �University Hospital of NorthStaffordshire, Staffordshire, UK; and §Pegional GeneralChildren's Hospital ‘Aglaia Kyriakou’, Athens, Greece

Purpose: An effort to understand the school life of children sufferingfrom epilepsy, in Greece – from the children's /parent's point of view.

Method: After appropriate consent, we interviewed 100 people, withopen ended questionnaires, from 10th October 2011 to 10th January 2012,in two hospitals of Athens: Evangelismos (20 adults aged 19–45) andChildren's Resional General Hospital ‘‘Panayotis & Aglaia Kyriakou’’(40 children and 40 parents). 38 parents, 34 children and 18 adults agreedto participate.

Result: 76.31% parents had never informed their children about theirdisease, either because they thought their children were too young toknow about their ‘situation’ or because they were scared of the possiblesocial consequences. They were worried that their children might be tar-geted if they openly discussed about epilepsy in school. There were con-cerns about bullying, exclusion from parties and games etc. However, allparents admitted that after being informed about epilepsy, they under-stood that ‘‘it is nothing more than a disease’’. 17.65% children and44.44% adults had no hesitation talking about their illness to the otherpupils at school whereas 62.5%parents, 58.82% children and 55.56 adultssaid they prefer to keep the illness a secret. All the interviewees addressedthe lack of information about epilepsy.

Conclusion: Even nowadays epilepsy is a cause of anxiety to thepatients, their families and social environment, including school, teachersand training staff. It seems crucial to improve the information about epi-lepsy, enhance people's understanding about this disease and generate ahappier school life for children, parents and teachers.

p754STUDY OF THE EXECUTIVE FUNCTION IN CHILDRENWITH BENIGN FOCAL EPILEPSY WITH CENTRO-TEMPORAL SPIKESM. L. G. Manreza, N. Banaskiwitz, C. S. M. G. Miziara,A. P. Valadares, and E. AmaroHospital das Cl�nicas of Medicine University os S¼o Paulo, SaoPaulo, SP, Brazil

Purpose: Cognitive alterations have been associated to benign focal epi-lepsy of childhood with centrotemporal spikes (BECTS) including theexecutive functions. We studied the performance of children with BEC-TS in attention and executive functions tests. All children were within thenormal QI.

Method: Fifty eight children with ages ranging from 8 to 13 years oldwere evaluated, 30 with BECTS and 28 control group. Battery testapplied: Cubes, Vocabulary, Digits, and Code subtests of the WechslerIntelligence Scale for children, Stroop test – Victoria version, WisconsinCard Sorting test, Phonemic Verbal Fluency (FAS), Trails test, Concen-trated Attention test and Tower of London.

Result: Children with left discharges and taking medication presentedthe performance lower in estimation of QI when compared to the controlgroup, right or bilateral discharge and without medication. The executiontime in card one of the Stroop test was higher in the study-group relativeto control and showed no significant difference regarding laterality of thedischarge and medication. Children with BECTS showed lower effi-ciency in FAS. Children with left discharge and without medicationshowed lower results. Relative to the Wisconsin Card Sorting test showedworse performances in the group with left discharge and the group with-out medication.

Conclusion: Children with BECTS showed lower results than the con-trol-group: verbal fluency and solving problems. Children with BECTSpresent limitations concerning cognition: some aspects of executive func-tion dependent of the discharge and the medication

p755AN ONGOING EUROPEAN NON-INTERVENTIONALREGISTRY STUDY OF PATIENTS WITH LENNOX-GAS-TAUT SYNDROME: INTERIM ANALYSISM. Nikanorova*, and I. Chouette�

*Danish Epilepsy Centre, Dianalund, Denmark; and �EisaiEurope Limited, Hatfield, UK

Purpose: Rufinamide is licensed in Europe for adjunctive treatmentof seizures associated with Lennox-Gastaut syndrome (LGS) inpatients aged ‡4 years. A non-interventional European registry study isongoing, to provide long-term data (‡3 years) on >100 LGS patientsinitiating rufinamide as add-on therapy and up to 125 LGS patientsreceiving other antiepileptic drugs (AEDs). Here we present an interimanalysis.

Method: The registry is enrolling LGS patients (age ‡4 years) requiringmodification to any AED treatment, including initiation of rufinamide.Its primary objective is to evaluate long-term safety. Effects of treatmenton seizure control and healthcare resource utilisation are also beingassessed. Eighty-one patients from 64 sites in 9 countries are currentlyenrolled. An interim analysis of the first 60 patients (37 male, 23 female)is presented; 47 having received rufinamide.

Result: At baseline, mean (standard deviation [SD]) age was 15.6(10.4) years; mean (SD) time since LGS diagnosis was 6.1 (8.5)years; and mean (SD) number of prior AEDs was 7.3 (3.8). To date,47/60 (78.3%) patients have been followed up for ‡1 year. Median(range) follow-up duration is 24.4 (3.3-40.1) and 27.7 (17.9-32.3)months for patients treated with rufinamide and other AEDs, respec-tively. AED-related adverse events have been reported by 25.5% and38.5% patients treated with rufinamide and other AEDs, respectively.One patient (in ‘‘other AEDs’’ group) has withdrawn due to an AED-related adverse event. No unexpected safety findings have emergedto date.

Conclusion: The registry is providing useful information on LGS and itsmanagement. Supported by Eisai

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p756LONG TERM EFFICACY AND HOSPITALIZATIONRATE IN CHILDREN WITH REFRACTORY FOCAL EPI-LEPSY TREATED BY VAGUS NERVE STIMULATIONM. Ryz�*, R. Kuba�, Z. Nov�k�, H. Oslejskova*, M. Br�zdil�, andI. Rektor�

*Epilepsy Center Brno, Brno University Hospital and Facultyof Medicine, Masaryk University, Brno, Czech Republic; and�Epilepsy Center Brno, St. Anne's University Hospital andFaculty of Medicine, Masaryk University, Brno, CzechRepublic

Purpose: The aim of the study is evaluation of long-term efficacy andhospitalization rate in children with refractory focal epilepsy treated byvagus nerve stimulation.

Method: We retrospectively analyzed 15 children with intractable focalepilepsy treated by vagus nerve stimulation. We analyzed the effective-ness at 1, 2 and 5 years follow-up. We counted the average number ofurgent hospitalizations and number of days of urgent hospitalization peryear for each patient before and after the VNS implantation.

Result: The mean seizure reduction was 42.5% at 1, 54.9% at 2 and58.3% at 5 years. The number of responders was 7 (46.7%) at 1 and 9(60%) at both 2 and 5 years (p<0.001 - in comparison to preoperative per-iod). The mean of number of urgent hospitalization per one patient was1.0€0.6 per year preoperatively and 0.3€0.5 per year postoperatively(p<0.0001). The mean of number of days of urgent hospitalization perone patient was 9.3€6.1 per year preoperatively and 1.3€1.8 per yearpostoperatively (p<0.0001).

Conclusion: Vagus nerve stimulation is an effective method in treatingchildren with refractory focal epilepsy. It leads to substantial decrease ofnumber of urgent hospitalizations and the reduction of its duration.

p757DIAGNOSTIC CHALLENGES IN A PATIENT WITHFOCAL CORTICAL DYSPLASIA TYPE IIB ANDBENIGN FOCAL EPILEPTIFORM DISCHARGES OFCHILDHOOD (BFEDC) IN ADDITIONN. BariÐic, T. Pieper, V. Ivanovic, P. Gr �dan, B. Bunoza,I. Lehman, and H. HolthausenUniversity Medical Centre Zagreb, Zagreb, Croatia

Purpose: Discordant findings in children with structural focal lesionslike FCD are not so rare, e.g. generalized epileptiform discharges (ED),ED distant from the lesion site or over the hemisphere contralateral to thelesion. Considerations in such situations include further epileptogeniclesions not visible on MRI, irritative spikes because of seizure spread,and idiopathic types of epilepsies in addition.

Method: Patient M.D. presented with non localizing/non lateralizingseizures at age of 3.EEG showed ED left centro-temporo-parietal. MRIraised the suspicion of a FCD left fronto-central. Repeated EEGsrevealed ED over changing localizations like left and right temporo-pari-etal, right frontal and left fronto-central (including polyspikes left fronto-central). Seizures were drug resistant and several hospitalizations werenecessary because of status epilepticus. A very high resolution MRI dur-ing presurgical evaluation confirmed a ‘‘bottom of sulcus dysplasia’’ leftfronto-central. The patient became seizure free after invasive recordingwith subdural grids and subsequent surgery. Pathology confirmed FCDtype IIb.

Result: EEG¢s at age of 14, 6 months post surgery, showed BFEDC rightfrontal and bi-occipital. Wake- and sleep-EEG normalized at age of 15.The boy is now off drugs and his school performance is excellent.

Conclusion: The co-existence of SFE plus BFEDC and/or Benign FocalEpilepsy of Childhood should be included early in considerations in chil-dren with discordant findings between MRI and EEG. The correct diag-nosis can be difficult particularly in cases with atypical BFEDC inaddition to an epileptogenic lesion. Recognition of such constellationmay have consequences for the choice of drugs and for the timing of pre-surgical evaluation.

Semiology, Aetiology and Classification 25Wednesday, 03 October 2012

p758DRAVET SYNDROME AND OTHER GENETIC ANDSTRUCTURAL CAUSES OF POST-VACCINATION EPI-LEPSY: A NATION-WIDE 10-YEAR COHORT STUDYN. E. Verbeek1, F. E. Jansen2, M. J. A. Van Kempen1, D.Lindhout1, N. A. T. Van Der Maas3, and E. H. Brilstra1

*University Medical Centre Utrecht, Utrecht, The Netherlands;�Rudolf Magnus Institute of Neuroscience, University MedicalCenter Utrecht, Utrecht, The Netherlands; and �RIVM,Bilthoven, The Netherlands

Purpose: Dravet syndrome is increasingly recognised as a genetic causeof alleged vaccination encephalopathy. However, little is known on theprevalence and underlying causes of post-vaccination epilepsy in gen-eral, and this information may have great impact on public acceptance ofvaccination programs. We investigated the outcome and aetiology of epi-lepsy following vaccination, in a national cohort.

Method: The medical data of all 1,269 children with seizures follow-ing vaccination in the first two years of life, reported to the NationalInstitute for Public Health and Environment in the Netherlands in1997–2006, were systematically reviewed. Of children with onset ofepilepsy within 24 hours after administration of an inactivated vaccine,or 5–12 days after an attenuated vaccine, follow-up data wereobtained.

Result: Follow-up (median age 10 years) was available for 23 of 26 chil-dren with epilepsy onset after vaccination. 11 children had developed epi-leptic encephalopathies, 4 children had encephalopathy predating theonset of epilepsy, and 8 children had normal cognitive outcomes. Geneticcauses were detected in 11 children: nine SCN1A-mutations (eight Dra-vet, one GEFS+ syndrome), one PCDH19-mutation (EFMR) and onesubmicroscopic 1qter deletion. Genetic causes were presumed to be pres-ent, but were not identified in four children with either neuronal migra-tion disorders or familial epilepsies.

Conclusion: In the majority of cases with post-vaccination epilepsy,genetic causes can be assessed (65%). Our study shows that normal cog-nitive outcome after post-vaccination epilepsy is also common (35%),but confirms that Dravet syndrome is the major cause of cases with post-vaccination encephalopathy (73%).

p759EPILEPSY IN CHILDREN WITH CEREBRAL PALSYO. JotovskaInstitute for Mental Health of Children and Youth, Skopje,Macedonia

Purpose: To present the frequency of epilepsy in children with C.P, epi-lepsy in different types of C.P. and the importance of the degree of mentalretardation in frequency and severity of epilepsy.

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Method: Files of 100 children are analyzed, age, sex, type of C.P., fre-quency and degree of mental retardation and number of children with epi-lepsy. Diagnostic procedures: brain ultrasound, CT and MNRI, EEGs,psychological testing were performed.

Result: 11 children of 100 with C.P. suffered from spastic quadriplegia,25 with spastic diplegia, 16 with spastic hemiplegia, 20 with hypotonicform of C.P., 12 with dyskinetic form and 16 with combinations of theforms mentioned above; 22 children suffer from epilepsy, 35 isolated orcombined anatomo-morphologic anomalies were described with the helpof imaging methods; EEG was not recorded in 8 children with C.P. Thechildren with epilepsy have epileptiform changes in their EEGs, 7 chil-dren did not present any epileptiform changes, 6 children presented non-specific changes, 31 children with focal changes, 26 with bilateralchanges and paroxysms. Concerning mental retardation, borderline intel-lectual functioning was observed in 5 children, mild mental retardation in13 children, moderate mental retardation in 6 children, severe mentalretardation in 9 children, disharmonic development in 6 children, delayin speech and psychomotor development in 38 children, normal develop-ment in 25 children.

Conclusion: Children with C.P. exhibit diverse spectrum of co-morbiddisorders such as epilepsy. The degree of mental retardation and neuro-logical deficit, especially spasticity has a positive correlation with the fre-quency and severity of epilepsy.

p760RESPONSE TO INTRAVENOUS IMMUNOGLOBULINSIN MALIGNANT MIGRATING PARTIAL SEIZURES ININFANCY: ONE CASE REPORTP. Morillo*, R. Buenache�, K. Escajadillo�, C. Mondrag�n�,A. Pedrera�, and G. Lorenzo�

*Ramon y Cajal University Hospital, Madrid, Spain; �HospitalRamon y Cajal., Madrid, Spain; and �Ram�n y Cajal UniversityHospital, Madrid, Spain

Purpose: To present one patient diagnosed with malignant migratingpartial seizures in infancy (MMPEI) with successful response to immu-nomodulatory treatment.

Method: We report a 19-month-old boy, without relevant medical his-tory, who debuted at 5 and 6 months of age with atypical febrile seizures.Neurological examination and complementary tests (CSF, EEG, CT andbrain MRI) were normal, being treated with valproate.

Result: From 7 months of age, the patient had recurrent episodes ofpolymorphic seizures with loss of consciousness, irritability, hypotonia,autonomic and left or right focal motor symptoms, as status epilepticus,in relation with febrile and afebrile infectious processes. We observed astop in his neurocognitive development and an autism-like behaviour.Sequential EEGs (awake and asleep) showed recurring seizures of bothbrain hemispheres. The neurometabolic study (blood / CSF), antineuro-nal antibodies, molecular analysis of gene SCN1A and GABRG2, werenormal. The patient was treated with a combination of levetiracetam, pyr-idoxine, ACTH / corticosteroids, lacosamide and ketogenic diet, with noclinical response so, iv gammaglobulins (IGIV) was associated (2 g/kg).At 12 months of age he had severe primary hypertriglyceridemia andhypercholesterolemia, requiring urgent plasmapheresis and stopping ke-togenic diet.

At present background medications include valproate, levetiracetam,lacosamide and IVIG, observing an improvement in neurological state,disappearance of paroxysmal EEG abnormalities and lack of seizures inthe last 7 months.

Conclusion: We identified seizure control in a patient with refractoryMMPEI after treatment with IVIG. We cannot rule out that he is in a sei-zure-free period due to the natural outcome of the disease.

p761CLINICAL AND EEG CHARACTERISTICS OF EPI-LEPSY IN PATIENTS WITH NEURONAL CEROID LIPO-FUSCINOSISR. Kravljanac*, J. Staropoli�, K. Sims�, N. J. Jovic�, andM. Djuric**Faculty of Medicine, Institute for Mother and Child Healthcareof Serbia, University of Belgrade, Serbia of Serbia, Belgrade,Serbia; �Harvard Medical School, Massachusetts GeneralHospital, Boston, MA, USA; and �Department for Neurologyand Psychiatry for Children and Youth, Medical School,Belgrade, Belgrade, Serbia

Purpose: Evaluation of clinical and EEG characteristics of epilepsy inchildren with neuronal ceroid lipofuscinosis (NCL) in the West Balkanregion.

Method: The study included NCL patients diagnosed by enzyme,genetic, and histopathologic analysis in the period 1991–2011. The epi-lepsy presentation, EEG findings and response to AEDs were evaluated.

Result: 17 patients (14 males, 3 females) were included: 16 with LINCL(12 with classical type, 4 variant) and one with JNCL. Seizures were theinitial manifestations at mean age of 2.8 years in all cases with CLN2,mainly preceded by hyperactivity. Ataxia and mental regression existedbefore epilepsy in the boy with CLN3 and two siblings with the Finnishvariant of LINCL (CLN5). All patients suffered different types of sei-zures: complex and simple focal with/without secondary generalization,myoclonus; five experienced status epilepticus and three epilepsia parti-alis continua. Polytherapy was required in 14 cases, often with sideeffects. EEG showed occipital discharges during slow-frequency phot-ostimulation suggesting diagnosis at early stage in four LINCL cases.Slowing and amplitude decreasing of background activity was obviouswith disease progression.

Conclusion: LINCL is the most frequent NCL type in the region. Sei-zures were the initial manifestations in all LINCL cases and were fol-lowed by poor controlled epilepsy with variation in clinical presentationof epilepsy, even among the children with the same NCL type ParticularEEG features are suggestible for diagnosis. Treatment of epilepsy inNCL patients is challengeable.

p762BEHAVIOURAL PROBLEMS AND EEG CHARACTER-ISTICS OF CHILDREN WITH BENIGN CHILDHOODEPILEPSY WITH CENTROTEMPORAL SPIKESR. SamaitieneVilnius University, Lithuania

Purpose: 1) To investigate the behavioural problems in children withbenign childhood epilepsy with centrotemporal spikes (BECTS), to com-pare with data of patients with peripheral nervous system disorders(PNSD); 2) To estimate the relationship of age when first seizureoccurred, duration of epilepsy and treatment, EEG spiking parameters,schooling data and behavioural problems.

Method: 23 patients with BECTS, 20 patients with peripheral nervoussystem disorders, aged 6–11 years, equally distributed for age and genderattending regular schools were investigated. Evaluation was made usingthe Lithuanian version of Child Behaviour Checklist (CBCL).

Result: Children with BECTS had significantly higher scores in Anx-ious/Depressed (5.0€2.9 vs 4.0€2.7, p=0.004), Social Problems (3.9€3.2vs 3.1€2.3, p=0.017), Attention Problems (5.7€3.0 vs 4.3€3.1, p=0.002)and Aggressive Behaviour (6.8€4.6 vs 5.3€4.0, p=0.003) subscales, com-pared with the patients with PNSD. There were significant relationshipsestablished in the BECTS patients group: 1) the higher were scores of

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Attention Problems subcale, the lower were grades native language (r= -0.560, p=0.03); 2) the longer was the treatment, the lower were gradesmathematics (r=-0.581, p=0.023); 3) the earlier was the beginning of sei-zures, the greater were the results of Delinquent Behaviour scores (r=-0.308, p=0.047). Presence of additional extrarolandic focus and focalspecific discharges spreading to centrofrontotemporal, centroparietotem-poral areas were related to higher scores of Social Problems, AttentionProblems and Delinquent Behaviour (r=0.421, p=0.018; r=0.543,p=0.002; r=0.361, p=0.04) in the BECTS patients group.

Conclusion: Children with BECTS are at risk for behavioural problems.Presence of discharge location other than centrotemporal was related tohigher scores of behavioural problems.

p763YIELD OF BRAIN IMAGING OF CHILDREN WITH SEI-ZURE FOLLOWING REFERRALS. Al-Ani, and A. MasQueen's University Hospital, London, UK

Purpose: To examine the yield of brain imaging among children andadolescents with seizure

Method: Rterospective analysis of prospectively collected data. 361Patients were categoriesed into two groups. Group I consisted of 245patients with normal neurological examination and normal neurodevel-opment. Group II consisted of patients (n=116) with abnormal neurologi-cal signs and or sepcific learning difficulties / global neurodevelopmentdelay. Idiopathic epilepsy was defined as only epilepsy. Brain abnormali-ties were considered non-significant if they were non-specific findingsand ulikely to cause seizure.

Result: Significant brain abnormalities were found in 49/361 (13.6%)patients. Of these, 16 patients (6.5%) were in group I and 33 (28.5%)patients were in group II.

Conclusion: Brain imaging should be considered for patients withseizures, normal neurological examination and normal neurodevelop-ment.

p764COMPARATIVE EMBEDDED CASE STUDY TOEXPLORE EXPERIENCES OF YOUNG PEOPLE WITHEPILEPSY AND THEIR PARENTS DURING TRANSI-TION FROM CHILDREN TO ADULT EPILEPSY SER-VICESS. A. LewisWalton Centre NHS Foundation Trust and Bangor University,Conwy, UK

Purpose: This study explores 1) Young people with epilepsy and theirparent's experience of communication, information needs and knowledgeexchange with healthcare professionals in two epilepsy services. 2)Which models of service delivery was effective during transition fromchildren to adult epilepsy services.

Method: Comparative embedded case study design using multiplesources of evidence. Ethical approval was obtained and 30 young peoplewith epilepsy aged between 13 and 19 years old and 21 parents partici-pated. Primary source of data collection methods were individual inter-views and focus groups. Two staged approach was used to analyse data;firstly thematic analysis of case study data and secondly pattern matchingand replication logic. Theory-based evaluation methods was used to con-

struct context, mechanism and outcome chains to understand why partic-ular models of service delivery work during transition, for whom andunder what circumstances.

Result: Joint epilepsy clinic facilitated by paediatrician, adult neurolo-gist and supported by an epilepsy nurse was found to be most effective.Continuity of care at staged intervals enabled young people to engagewith adult healthcare professionals once transitioned to adult services.Age-appropriate information improved self-management skills by youngpeople whereas information lacking clarity caused psychological prob-lems. Majority of young people had difficulty remembering information.Psychological care was inadequate. Majority of parents lacked basicinformation to encourage their child to safe self-care. Translation of poli-cies and guidelines into clinical practice was weak.

Conclusion: This study makes significant contribution to understandingto what constitutes good communication and good transition from theperspective of young people with epilepsy and their parents.

p765A PILOT STUDY INVESTIGATING THE EFFECT OFCHILDHOOD EPILEPSY ON SIBLINGS’ QUALITY OFLIFES. Memon*, V. Burch�, and K. Das�

*University of Aberdeen, Aberdeen, UK; �Young Epilepsy,Lingfield, UK; and �Great Ormond Street Hospital for ChildrenNHS Trust, London, UK

Purpose: Literature examining the effects that epilepsy has on non-affected siblings is extremely sparse. Therefore, the aim of our study wasto assess the quality of life and main concerns of children who have sib-lings with epilepsy compared to a control group of children who have sib-lings with other neurological conditions.

Method: Cases and controls were prospectively recruited from ‘YoungEpilepsy’, a centre for children and young people with complex epilepsyand other neurodisabilities. Participants completed a detailed postal ques-tionnaire asking about their concerns. Quantitative and qualitative datawas collected.

Result: Thirty-one questionnaires were returned from the case groupand eight from the control group. Main concerns amongst the cases wereinjury (89%) or death (77%) of their siblings due to seizures. A greaterproportion of cases said that their affected sibling got more attention, butmost felt that this was a good thing. Despite the cases having more severeco-morbidities, worries about learning difficulties and behaviour weremore common in the control group. Both groups expressed that their sib-ling's disability had made them more caring and sympathetic, strength-ened their family and helped them to deal with stress.

Conclusion: Our pilot study found no major differences between casesand controls. Although it is evident that children who have a sibling withepilepsy express some negative effects, including feeling worried abouttheir sibling's well being and health, these individuals also report manypositive feelings and on the whole it appears they are functioning welland have a positive outlook on life.

p766PARENTAL REACTIONS IN BENIGN CHILDHOODFOCAL SEISUREST. ValetaSt.Thomas’Hospital, London, UK

Purpose: To document Parental Reactions and Needs in Benign Child-hood Focal Seizures (BCFS).

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Method: My personal interest started in 2000 when speaking exten-sively with parents of children with BCFS I realized that they were con-cerned for many more issues than the seizures themselves and other thanthose that they were discussing with their physician. They had dramaticexperiences and many unanswered questions and anxieties. Conse-quently, I have designed a questionnaire and initiated an ongoing pro-spective study. The questionnaire contains 34 questions aiming to defineand analyze the psychosocial effects of BCFS on parents and children,their attitude about epilepsy, their reactions, concerns about the progno-sis, necessity of evaluation and needs. Thirty one parents participated inthis study.

Result: Panic, fear, anxiety, shock, terror and thoughts about death werethe most common subjective parental complaints. Their sleep and thequality of their work was affected. Half of the parent's behaviour towardsthe child changed. Most of the parents expressed the need for educationon epilepsies, psychological support for the child, and themselves. Theyalso expressed the need to participate in groups of parents with the sameproblem.

Conclusion: Despite the excellent prognosis of BCFS, parental reac-tions are severe. There is a need for family management, education andpsychological support. That should be properly addressed from the timeof first diagnosis and thus eliminate anxiety and improve the quality oflife of the child and family.

p767VIDEO-EEG MONITORING IN DIAGNOSTICS OF EPI-LEPTIC AND NON-EPILEPTIC PAROXYSMAL CONDI-TIONS IN CHILDRENV. I. Guzeva, and O. V. GuzevaSaint-Petersburg pediatric medical academy, Saint-Petersburg,Russian Federation

Purpose: The aim of the study was to determine the diagnostic effi-ciency of video-EEG monitoring in children with paroxysmal disordersof consciousness.

Method: The study included 259 children from 1month to 18 years,among them 103 (39.8%) were girls and 156 (60.2%)- boys. All chil-dren were referred to nervous diseases department to clarify the diag-nosis and selection of appropriate treatment. 80.69% of childrenadmitted with diagnosis ‘‘epilepsy’’, 19.31%- with non-epileptic par-oxysms.

Result: The results of comprehensive survey based on video-EEG moni-toring allowed to established in 163 (62.93%) cases epilepsy, mostlysymptomatic, in 66 (40.49%) – partial and in 16 (9.82%)- generalizedform. In 68 (41.72%) cases was diagnosed cryptogenic partial epilepsy,in 3 (1.84%)- Landau-Kleffner syndrome and in 10 (6.14%)- idiopathicepilepsy. Diagnosis of non-epileptic paroxysms was specified in 96(37.07%) cases. Among them 44 (45.83%) were sleep disorders (para-somnias), 21 (21.88%)- neurotic states, others non-epileptic paroxysmsestablished in 26 (27.08%) and ADHD- in 1 (1.05%) cases. Was found asignificant difference in frequency of identification of epileptiform activ-ity on EEG with video monitoring during sleep compared with other vari-ants of EEG recording. Detection of epileptiform and epileptic activityduring video-EEG monitoring compared with routine EEG increases in3.7 times.

Conclusion: Using the results of video-EEG monitoring (awake andsleep) significantly increases the possibility to correct diagnosis andappropriate treatment. Invaluable help in differential diagnostics of epi-leptic and non-epileptic paroxysms and clarification forms of epilepsy inchildren provides the registration of the paroxysm during video-EEGmonitoring.


p768VAGUS NERVE STIMULATION IN PEDIATRIC EPI-LEPSY PATIENTS: IS THIS REALLY WORTHWHILE?V. C. Terra, M. A. Nisyiama, A. C. Sakamoto, and H. R. MachadoHospital das Cl�nicas da Faculdade de Medicina de Ribeir¼oPreto, Ribeir¼o Preto, SP, Brazil

Purpose: Intractable epilepsy in children is has a negative impact incognitive and behavioral skills, and in quality of life. In this aspect, sei-zure control with minimal side effects should be pursued. In patients thatressective surgery is not possible, alternative treatment such as ketogenicdiet or vagus nerve stimulation (VNS) should be considered. AlthoughVNS therapy is available for many years, there are few studies demon-strating its effectiveness in children.

Method: We analyzed 36 patients up to 18 years old, with medicallyintractable epilepsy submitted to vagus nerve stimulator implantation.We considered the age at surgery, the seizure type, the pathological find-ings, seizure outcome, number of hospitalizations and behavioralchanges. Data were prospectively collected, according to the protocols ofour institution's ethics committee.

Result: 55.6% were boys. A reduction of at least 50% of seizures wasachieved in 61.3% of the cases and 12.1% of the patients had more than90% of seizure frequency reduction. Also, 47.2% of the patients neededfrequently hospitalization before VNS implantation and in follow up thisnumber dropped out to 8.3%. The patient who died, one from sepsis andthe other in the immediate post-operative period of a callosotomy.

Conclusion: VNS demonstrated to be effective in reducing seizure fre-quency and need of hospitalization in children with very refractory epi-lepsies and should be considered as an option even in countries withlimited resources.

p769THE EFFECT OF BODY TEMPERATURE IN SEIZURESASSOCIATED WITH ROTAVIRUS GASTROENTERITISY. S. Kwon*, B. Kang*, and D. W. Kim�

*Inha University Hospital, Incheon, Korea; and �Inje UniversityIlasnbaik hospital, Goyang, Korea

Purpose: To evaluate the effect of body temperature in seizures associ-ated with rotavirus gastroenteritis.

Method: Medical charts of infants and children who had been admittedto the pediatric department of Inha University Hospital between July1999 and June 2011 due to seizures associated with rotavirus gastroenter-itis were reviewed. Subjects were initially divided into two groups on thebasis of the presence/absence of fever during seizure; ‘febrile seizure’,‘afebrile seizure’. Afterwards, subjects in the ‘afebrile seizure’ groupwere divided into two subgroups according to the presence/absence offever during the entire period of illness; ‘afebrile seizure with fever’, ‘afe-brile seizure without fever’. Comparison between the three groups wascarried out.

Result: Among the 75 patients that were admitted due to seizures associ-ated with rotavirus enteritis, 17 patients (23%) were included in the ‘feb-rile seizure’ group and 42 patients (56%) in the ‘afebrile seizure’ group.Among the ‘afebrile seizure’ group, 19 subjects (32%) had fever duringthe illness, while 23 subjects (39%) were afebrile during the illness.Patients with febrile seizures were most likely to develop seizure earlier,while afebrile seizure patients without fever during the illness were mostlikely to develop seizure later (1.29€0.77 vs. 2.47€0.90 vs. 3.09€0.95days; p<0.0001). Episodes of seizure were less frequent in the ‘febrile

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seizure’ group showing significant difference (1.7€1.0 vs. 2.8€1.1 vs.3.3€1.8 episodes; p<0.01).

Conclusion: Results of our study has revealed that body temperaturemay influence the characteristics of seizures associated with rotavirusenteritis, in which differences of the degree of inflammation may play arole. Further studies in the future are needed to clarify this difference.

p770ELECTRO-CLINICAL ASPECTS OF FOCAL SYMP-TOMATIC EPILEPSY OF CHILDHOOD WITH SECOND-ARY BILATERAL SYNCHRONY PHENOMENON ONEEGA. Bunduchi*, A. Bunduchi�, and S. Hadjiu**State University of Medicine and Pharmacy, ‘‘Nicolae Testemitanu’’, Chisinau, Moldova; and �Chisinau, Moldova

Purpose: To identify seizure semiology and EEG patterns in childrenwith focal symptomatic epilepsy.

Method: Study included 65 patients – 38 boys and 27 girls, age 4 monthsto 18 years, followed-up 6 months to 4 years; divided in 2 groups accord-ing to the age at seizures onset. Patients were evaluated neuropsychologi-cal, by neuroimaging (neurosonography, CT or MRI) and video-EEGmonitoring (1–12 hours).

Result: Semiology of onset seizures was: febrile seizures - 12% cases (Igroup), GTCS in 21% (I group) and 46% (II group), tonic seizures in 32%(I group) and 2% (II group), atypical absences in 20.9% (I group) and18% (II group), and partial seizures – 18% (I group) and 31.1% (IIgroup). Three seizure types occured in 28% cases (I group) and 26%cases (II group); two types - in 64% patients (I group) and 35% cases (IIgroup), single seizure type - in 17% cases (I group) and 8% cases (IIgroup). Neuropsychological tests revealed cognitive impairment in 82%(I group) and 42% (II group). Interictal EEG changes were representedby: basic EEG slowing, theta-delta regional slowing, regional epilepti-form activity combined with diffuse epileptiform patterns – secondarybilateral synchrony phenomenon. Ictal patterns include atypical absences(24%), myoclonic seizures (8%), eyelids epileptic myoclonus (2%), andtonic seizures (21%).

Conclusion: Focal symptomatic epilepsy associated with secondarybilateral synchrony phenomenon on EEG includes a large polymorphismof epileptic seizures, cognitive impairment and has a poor outcome. EEGchanges are represented by regional epileptiform activity combined withdiffuse epileptiform patterns.

p771CARBON MONOXIDE AND SEIZURES IN CHILDRENA. Gniatkowska-NowakowskaOutpatient Clinic of Child Neurology and Epileptology, Kielce,Poland

Purpose: Carbon monoxide (CO) poisoning has many severe complica-tions. Between them is the stimulation of early and late seizures in chil-dren group

Method: We respectively reviewed 16 patients who had seizures afterCO intoxication. There were 9 girl and 7 boys with a mean age of 9.1(range 2 to 17 years). The observation time for those patients was 5 yearsafter the poisoning

Result: A total 16 children with early seizures were analyzed. Duringthe observation time there was no deaths among the study group. A mag-netic resonance scan of the brain (1.5T) was performed 6 months after theCO poisoning. It revealed abnormalities in the brains of 5 children (31%

of the study group) in the following areas: globus pallidus (2 children),subcortical white matter (1 child), hippocampus (1 child), cerebellum (1child). Early seizures were presented in all children, late seizures (above7 days after CO poisoning) were identified in 7 children. The clinical pre-sentation of late seizures was tonic – clonic seizure (5 children) and mio-clonic seizures (1 child). Loss of consciousness were in 10 children(62.5%). Four children developed epilepsy during 2 years after CO poi-soning.

Conclusion: Severe and medium degree of CO in blood may cause lateseizures and trigger epilepsy, especially in the group of young children.Delayed neurologic sequelae (DNS) were a high risk factor of epilepsy.Hyperbaric oxygen therapy is recommended in patient with DNS and COintoxication related unconsciousness.

p772AUTOANTIBODY TO GLUTAMIC ACID DECARBOX-YLASE IN A 2-YEAR OLD GIRL WITH THERAPY-RESISTANT EPILEPSYS. Saltık, and E. Y. KaratoprakIstanbul Medeniyet University Goztepe Educational andTraining Hospital, Istanbul, Turkey

Purpose: Glutamic acid decarboxylase is the enzyme that synthesisgamaaminobutyric acid which is the major inhibitory neurotransmitter inCNS. Increased titres of Glutamic acid decarboxylase (GAD) antibodiesis common in type 1 diabetes mellitus patients. High anti-GAD titres israrely seen in neurological disorders such as epilepsy. In this study, wereport a case presenting with drug-resistant epilepsy with a high titer ofanti-GAD antibodies as an unusual cause of epilepsy since she was theyoungest case in the literature to our knowledge.

Method: A 2-year-old girl with a history of frequent complex partial sei-zures for 2 days was admitted to our child neurology deparment. To findout the cause of the epilepsy, all routine blood tests, imagings weredetected and antiepileptic treatment was started.

Result: Seizures which lasts 30 seconds–2 minutes were 3–10 times in aday. Neurological examination, laboratory findings, metabolic analysis,neuroimaging findings and sleep electroencephalography (EEG) werefound all normal. Her seizures did not respond many anti-epileptic drugtherapy. A high titer of anti-glutamic acid decarboxylase (GAD) antibod-ies was detected in the patient's serum but not in cerebrospinal fluid(CSF). Seizures responded to intravenous immunoglobulin treatment.Anti-thyreoperoxydase (TPO-Ab) positive hypothyroidism was alsodetected.

Conclusion: In conclusion anti-GAD antibodies should be investigatedin drug-resistant epilepsy even in younger children.

p773ATYPICAL EVOLUTION OF PANAYOITOPOULOSSYNDROME INTO CHILDHOOD ABSENCE EPILEPSY:A CASE REPORTK. Skiadas, T. Tsaprouni, and A. CovanisSt. Sophie's Paediatric Hospital, Athens, Greece

Purpose: Panayiotopoulos syndrome (PS) is a ‘‘benign’’ childhood focalepilepsy, which manifests primarily with autonomic, mainly emeticsymptoms and has a very good prognosis. Childhood absence epilepsy isidiopathic generalized epilepsy characterized by typical absence seizuresassociated with bilateral, synchronous and symmetric generalized spike-and-wave discharges at 3 cycles per second.

Method: We report a seven year old boy with clinical and electroen-cephalographic features of PS that showed atypical evolution. He is a

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right-handed neurologically normal boy with unremarkable personal andfamily history. At the age of 4 years, during nocturnal sleep, he presentedwith an episode during which his eyes and head deviated to the left, fol-lowed by vomiting and impairment of consciousness. This episode lastedten minutes. The EEG showed right temporal occipital spikes followedby slow waves. This type of seizure was repeated on three occasionswithin six months and the child was put on carbamazepine.

Result: He had been seizure-free for two years when during a follow-upvideo-EEG recording episodes of ‘‘absences’’ in association with gener-alized spike-and-wave discharges 2.5cycles per second of 5–6 secondsduration, were recorded. In addition, the interictal EEG continue to showright temporal occipital spikes followed by slow waves. The absence sei-zures were treated with valproic acid and carbamazepine was withdrawn,with complete response.

Conclusion: The presence of childhood absence epilepsy in childrenwho initially present with PS is very rare. It is difficult to understand thecoexistence, in the same patient, of the two different types of epilepsy.Probably there is a genetic relationship between them.

p774CLINICAL AND ELECTROPHYSIOLOGICAL CHAR-ACTERISTICS OF PATIENTS WITH PAROXYSMALDISORDERS. CLINICAL-ELECTROPHYSIOLOGICALCHARACTERISTIC OF PATIENT WITH PAROXYSMALDISORDERSM. Y. FominaPediatric Academy, Sanct-Petersburg, Russian Federation

Purpose: Structure of paroxismal disorders of children

Method: Clinical examination, EEG, MRI scan

Result: In St. Petersburg State Pediatric Medical Academy from 2009 to2011 were examined in 1286 patients aged 1 month to 18 years. The sur-vey was conducted neurologist, specialist functional offices, laboratoryand MRI diagnostics. Paroxysmal disorders and identified changes dur-ing the EEG served as a pretext for seeking advice from 425 people(33%). Complaints about the delay in psychomotor and language devel-opment, sleep disorders, behavioral changes, headache, dorsalgia, dizzi-ness, tics, enuresis, at least - progressive motor, visual, or cognitiveimpairment, reported in 726 people (56.5%). 79 (6.2%) patients wereexamined in connection with a closed head injury. In the structure of aviolation of paroxysmal epileptic paroxysms in our study were 51.2%. Ofthe 326 children with paroxysmal disorders established diagnosis of epi-lepsy in 167 cases, the debut of the disease was recorded in 59 children,others have already asked for specialized medical care. Antiepileptictherapy received 77 patients, 19 patients did not take drugs or violatingtheir assigned mode of reception of anticonvulsants. As for the single epi-leptic paroxysm checked with 12 patients (7.1%). Dominated by partialsymptomatic epilepsy with frontal and temporal localization of thesource. Among the generalized idiopathic form usually diagnosed in chil-dren and absans and juvenile myoclonic epilepsy. Symptomatic general-ized epilepsy syndromes are West and Lennox-Gastaut syndrome. Westsyndrome - the age-dependent epileptic syndrome related to the group ofinfantile epileptic encephalopathy was diagnosed in three infants. Thepatients were symptomatic infantile spasms and mental regression andmotor skills. Lennox-Gastaut syndrome was observed in one patient.Early infantile epileptic encephalopathy syndrome (Otahra) recorded inthe patient at age 3 months, suffered a hypoxic-ischemic CNS damagesevere. Benign epilepsy of infancy (Watanabe's syndrome) was diag-nosed in two patients 5 and 7 months. Among the most common non-epi-leptic seizures recorded syncope, parasomnias, and affective-respiratoryattacks.

Conclusion: In structure of paroxismal disorders in our study the epilep-tic paroxisms made 51%/ Among them the domineering ones were partialsymptomatic epilepsies (68%).

p775CLINICAL FEATURES AND OUTCOMES IN FEBRILEINFECTION-RELATED ACUTE EPILEPTIC ENCEPHA-LOPATHYJ. Garc�a-PeÇas*, S. Aguilera-Albesa�, J. Dom�nguez-Carral*,M. Yoldi-Petri�, T. Dur�-Trav��, A. Duat-Rodr�guez�, andM. L. Ruiz-Falc��

*Marqu�s de Valdecilla Hospital, Santander, Spain; �NavarraHospital, Pamplona, Spain; and �NiÇo Jesffls Hospital, Madrid,Spain

Purpose: The term ‘‘febrile infection-related epilepsy syndrome’’(FIRES) has been proposed to characterize the features of patients withacute epileptic encephalopathy during a febrile infection. A commonaetiology remains obscure.

Method: This retrospective multicenter case series reports on the clini-cal characteristics and outcomes of six patients with acute epilepticencephalopathy.

Result: Six previously healthy boys with a median age of eight years (5–12) presented to hospital with generalized tonic-clonic or secondarily gen-eralized seizures that appeared 2–10 days after initial symptoms of febrileinfection. All cases developed refractory epileptic status with a medianduration of 30 days (14–60) and required barbiturate-induced coma (0–47days). Adjuvant immunotherapy were administered in all. In two cases,reversible hepatic failure were noted. Initially, electroencephalographyshowed diffuse slowing. Persistent bifrontal or fronto-temporal dischargesoccurred later on. Ancillary studies including blood, urine, and cerebrospi-nal fluid samples, muscle mitochondrial studies and genetic mutation anal-ysis (POLG1 and SCN1A) were unrevealing. Cerebral magneticresonance imaging showed non-specific frontal abnormal signals in threepatients. Left frontal hypoperfusion was detected by SPECT in one caseduring the acute phase. All six patients experienced focal refractory sei-zures during follow-up (6–84 months). Motor handicaps and mild to mod-erate cognitive decline were noted in 4 patients. Two children had severesequelae. Their behaviour was hypoactive or impulsive (50%).

Conclusion: The clinical profile and outcomes of these six patients issimilar to the previously described as FIRES. This epileptic encephalopa-thy has an abrupt onset and is followed by refractory focal epilepsy offrontal predominance.

p776EARLY ONSET OF CORTICAL THINNING IN CHIL-DREN WITH ROLANDIC EPILEPSYG. M. Overvliet*, R. Besseling�, S. V. D. Kruijs�, J. Vles�,J. Jansen�, P. Hofman�, S. Ebus�, A. De Louw�, A. Aldenkamp�,and W. Backes�

*Maastricht University Medical Center, Maastricht, TheNetherlands; and �Kempenhaeghe, Heeze, The Netherlands

Purpose: Rolandic epilepsy is an idiopathic childhood epilepsy associ-ated with language impairments. It is investigated whether Rolandic epi-lepsy is associated with abnormalities in cortical thickness, and whetherthese abnormalities are associated with declined language performance.

Method: 24 children (age 8–14 years) with a clinical diagnosis of Rolan-dic epilepsy were compared with 24 age-matched healthy controls. TheClinical Evaluation of Language Fundamentals (CELF) test was used forlanguage evaluation. Structural T1-weighted MRI was performed at 3Tesla (voxel size 1x1x1 mm3) to enable automated quantitative assess-ment of cortical thickness. Linear regression was used to test for differ-ences between patients and controls and to assess the effect of age andlanguage indices on cortical thickness.

Result: For patients the core language score (mean€SD: 92€18) waslower than for controls (106€11, p=0.0026) and below the norm of 100

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(p=0.047). Patients showed specific impairments with respect to the normin receptive language (87€19, p=0.002) and language content (87€18,p=0.0016). The cortex in patients was significantly thinner (p<0.05, mul-tiple-comparisons corrected) in the postcentral, supramarginal and supe-rior temporal gyrus of the left hemisphere (receptive language area).Predominantly in left fronto-temporal regions, significant cortical thin-ning with age was found in patients only.

Conclusion: Reduced cortical thickness was found in Rolandic epilepsyin a language mediating area. Furthermore, early onset of cortical thin-ning was observed in multiple language mediating areas. These abnor-malities represent subtle but significant pathomorphology of thelanguage system and suggest thatRolandic epilepsy should not be consid-ered merely as a benign condition.

p777BUT… DOES MY DAUGHTER NOT SUFFER A MITO-CHONDRIAL DISEASE? CO-MORBID DRAVET SYN-DROMEM. Ru�z-Falc�-Rojas*, V. Cantarin-Extremera*, J. Garc�a-PeÇas�, A. Duat-Rodriguez1*, L. L�pez-Mar�n*, andL. Gonz�lez-Guti�rrez-Solana**NiÇo Jesus Hospital, Madrid, Spain; and �Marqu�s deValdecilla Hospital, Santander, Spain

Purpose: Dravet syndrome is a catastrophic epilepsy syndrome withcognitive delays and autistic behaviour. It is associated with mutations inthe SCN1A gene. A similar clinical feature is found in patients with mito-chondrial disease, this causes confusion and diagnostic delays.

Method: This a case report

Result: Around 3 months of age after the first vaccine of polio-DTP, thepatient presented status epilepticus with no fever. During her first year oflife she had hemiclonics seizures, every 2–4 weeks, and other seizureswith variable features, with and without fever. When she was 7–8 monthsshe had myoclonics too. She had normal psychomotor development untilshe was 6 months of age, after that she had a motor and language delay.The complete diagnostic evaluation included: a cranial magnetic reso-nance, cariotypes, a metabolic disease study…all were normal. When shewas 4 years old, a muscle biopsy demonstrated complex IV dysfunction.In this patient, when valproic acid decreased from 100 mg/l, the seizuresincreased. We reviewed her medical history and suspected a feature con-sistent with the Dravet syndrome. A mutation in SCN1A was found.

Conclusion: Our patient underscores the need to rule out possible co-morbid mitochondrial disease and Dravet syndrome. This is importantbecause the treatment for each type of seizure is different, with valproicacid being first line treatment in Dravet syndrome and contraindicated inmany mitochondrial diseases. Failure to pursue complete diagnostic eval-uation might influence in medication choice, possible seizure control anddevelopmental outcomes. Nowadays, there is not an entirely obviousexplanation for this association.


p778A CLINICAL AUDIT OF PROCESS AND OUTCOME OFEMERGENCY TREATMENT FOR PROLONGED EPI-LEPTIC SEIZURES IN CHILDREN ATTENDING ANEMERGENCY DEPARTMENTE. Joslin*, C. Dieppe�, and W. P. Whitehouse**University of Nottingham, Nottingham, UK; and �NottinghamUniversity Hospitals, Nottingham, UK

Purpose: The aim was to assess the guideline compliance and outcomesof pre-hospital and Emergency Department (ED) treatment of prolongedconvulsive epileptic seizures in children.

Method: This retrospective observational study included all childrenunder 18 years attending a teaching hospital ED who were treated forprolonged convulsive seizures 21-11-2010 to 21-11-2011. Cases wereascertained from the electronic database and medical notes werereviewed, data captured with a standard proforma, and transferred to anSPSS database. The local departmental and United Kingdom guidelineswere the audit standards, and outcomes compared to the literature. Sim-ple descriptive statistics, Chi-squared, and independent samples t-testwere used.

Result: There were 43 episodes in 37 patients, 20 male (54%) aged 10months to 16 years (median 4 years). Of 76 children given pre-hospitaltreatment and presenting to the ED during this period, 49 (65%) hadstopped seizing and 27 were still seizing and so received treatment in theED. About half had Rectal Diazepam from the ambulance crew, half Buc-cal Midazolam (BM) from their carers. Only 16 (37%) of the children'sepisodes treated in ED had had no pre-hospital emergency treatment. 25/43 (58%) treatments in ED (90% BM) stopped the seizure within 10 min-utes, 7/25 relapsed within 1 hour, 9/43 required respiratory support, 13were admitted to Paediatric Intensive Care. BM doses were often lowerthan recommended, and iv phenytoin often delayed, while paraldehydewas given.

Conclusion: Pre-hospital treatment was effective. ED treatment oftenunder-dosed BM, and the use of phenytoin was often delayed: practicesthat will be addressed locally.

p779APPLICATION OF NEW ILAE CRITERIA FOR DRUGRESISTANT EPILEPSY IN CHILDREN IN CLINICALPRACTICEM. A. De La Morena Vicente, J. Herreros Rodriguez, A. GarciaRon, R. Blanco Lago, L. Ballesteros Plaza, and J. Jensen VeronHospital Universitario Infanta Cristina, Madrid, Spain

Purpose: The International League Against Epilepsy (ILAE) has pro-posed new criteria to define drug resistant epilepsy. Epilepsy in childrendisplays clinical and therapeutic differences with respect to adults. Wehave applied these criteria to our outpatients pediatric.

Method: We reviewed medical records of forty children with epilepsyon our database, we excluded patients with less than one year of followup, with only one seizure or febrile seizures.

Result: Level 1 for categorizing of treatment outcome, we described theabove mentioned category in the last visit. With respect to seizure con-trol: Category 1, seizure free (50%); Category 2, treatment failure (20%);Category 3, undetermined (30%). Each category is subdivided into A(no), B (yes), C (undetermined) based on outcome with respect to adverseevents: 1A (47.5%), 1B (0%), 1C (2.5%), 2A (12.5%), 2B (5%), 2C(2.5%), 3A (22.5%), 3B (0%), 3C (7.5%).

For Level 2 classification of drug responsiveness of epilepsy, weobtained the following data: drug responsive (50%), drug resistant(22.5%), undefined (27.5%). Considering the pharmacological treatment,52.5% was in monotherapy and 47.5% in combination: drug responsive(40% and 10%), drug resistance (0% and 22.5%), undefined (12.5% and15%) respectively.

Conclusion: This study shows a greater number of patients classified asundefined with respect to studies in adults, and demonstrates the difficul-ties of application of these criteria in pediatric patients. It would be inter-esting that future studies included both populations.

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p780VAGUS NERVE STIMULATION IN A NEW PATHWAYWITH ANTI-INFLAMMATORY CYTOKINESV. Cantarin-Extremera*, M. Ru�z-Falc�-Rojas*, M. Ramirez-Orella*, J. Asensio*, M. P�rez-Jim�nez�, A. Duat-Rodriguez1*,and B. Rivero**NiÇo Jesus Hospital, Madrid, Spain; and �Hospital InfantilUniversitario NiÇo Jesffls, Madrid, Spain

Purpose: Electrical stimulation of the vagus nerve is a treatment forpatients with refractory epilepsy and depression. An anti-inflammatorypathway has been identified recently. In a few articles, a significantincrease in circulating cytokines after vagus nerve stimulation treatmentwas observed. We want to know mechanism may occur via vagally medi-ated actions on cytokine synthesis.

Method: Prospective study with 5 patients with refractory epilepsy, andfuture candidates will be added. The period studied is from one weekaverage prior to, and 1, 3 and 6 months following, implantation of a vagusnerve stimulator (VNS). No medication changes were made during thecourse of the study. High-sensitivity ELISA kits were used to measureplasma IL-6, IL-10 and IL-8. Cortisol, C-reactive protein (CPR) andimmune reconstitution were measured. We measured same cytokines incontrol group with VNS implantation more than 2 ayes ago.

Result: There was significant decrease in the plasma levels of IL-6.Increases seen with IL-8 and cortisol were not significant. IL10 was simi-lar. Plasma CRP and levels of CD4 and CD8 lymphocytes wereunchanged. All patients had seizures reduction.

Conclusion: VNS is associated with peripheral decreased in anti-inflammatory circulating cytokines. Such changes are unlikely to be non-specific inflammatory reactions, reflected by CRP levels. In view of gath-ering evidence supporting a role for the immune system in modulatingaffect, as well as seizure activity, these effects of VNS may be therapeuti-cally relevant. These data require replication in a larger, controlled study.

p781THE PROGNOSTIC FACTORS OF ACUTE ENCEPHALI-TIS IN CHILDRENJ. S. Lee, J. W. Kang, H. Kang, and H. D. KimSeverance Children`s Hospital, Seoul, Korea

Purpose: The long term outcome of acute encephalitis is very variable.The purpose of our study was to evaluate the prognostic factors that caninfluence to patient`s prognosis.

Method: Of 157 children who were admitted for acute viral encephalitisfrom 2006 to 2011, 78 children were qualified for follow-up evaluations.We divided patient's group into favorable outcome (n=48) and poor one(n=30). We compared the etiologies, clinical courses, the neuroimagingand electroencephalographic findings between two groups.

Result: The etiologies were identified in 17 cases in CSF (24%). Themain associated agents were herpes simplex (9 children; 53%), enterovi-ruses (3 children; 18%), varicella-zoster (1 child; 5.5%), measle virus (1child; 5.5%), and bacterias (3 children; 18%). 73 patients showed abnor-mal electroencephalographic findings (94%). The most common compli-cations were cognitive dysfunctions (60.8%), and seizure disorders(50.6%). The significant risk factors in poor group were initial history ofseizures (p=0.04), status epilepticus (p=0.03), mood change (p=0.009),cognitive dysfunction (p=0.018), and ICU admission (p=0.0326). As theinitial time of immunoglobulin treatment is earlier, the prognosis werebetter (p=0.037).

Conclusion: About 30% of children presented persisting sequelae afterencephalitis. The significant risk factors for sequelae were initial historyof seizure, cognitive problems, and mood change, status epilepticus and

ICU admission. Children who made a full recovery did so within 6months, which suggests that all children with encephalitis should be mon-itored for 6 months after the acute illness.

p782STRESS SENSITIVITY OF CHILDHOOD EPILEPSY:WHICH CHILDREN SEIZE UNDER STRESS?J. S. Van Campen, F. E. Jansen, L. C. Steinbusch, M. Joels, andK. P. J. BraunRudolf Magnus Institute of Neuroscience, University MedicalCenter Utrecht, Utrecht, The Netherlands

Purpose: To address the effect of stress on seizure frequency in childrenwith epilepsy and evaluate which clinical characteristics of these childrenrelate to stress sensitivity of seizures.

Method: Parents or caregivers of children with active epilepsy (aged 2to 16 years) were sent questionnaires on epilepsy characteristics, anti-epi-leptic treatment, psychomotor development, life-time stress exposure,and the effect of stress on seizure frequency in their child. Stress sensitiv-ity of seizures was divided in increased seizure frequency during stressfulperiods, and seizures provoked by acute stress. The relations betweenpatient and epilepsy characteristics and stress sensitivity of seizures wereanalysed using multivariable regression models.

Result: Hundred-fifty-three children were included in this study ofwhom 51% reported precipitation of seizures by stress. An increase inseizure frequency during periods of stress was reported in 39% of chil-dren. Seizures precipitated by acute stress were reported in 37%. Therewas a large overlap between patients reporting emotional and patientsreporting physical stress to be a precipitating factor.

A higher number of negative life events experienced in total life wasrelated to an increase in seizure frequency in stressful periods (OR 1.3,p=0.011) as well as to precipitation of seizures by acute stress (OR 1.3,p=0.020).

Conclusion: Stress sensitivity of seizures is very often reported andseems to be related to experienced negative life events. This relation maybe explained by a changed regulation of the hypothalamic-pituitary-adre-nal axis by (early life) stress. A larger hormonal response to daily stres-sors then increases the likelihood of stress to induce epileptic seizures.

p783ABSENCE SEIZURES DURING AWAKE AND SLEEP:WHAT IS A DIFFERENCE?B. Jocic-Jakubi, A. Al Tawari, L. Cindro Heberle, M. Pavlovic,and J. Ibrahim Al AnsariAl Sabah Hospital, Kuwait City, Kuwait

Purpose: To analyze neurophysiological features of absence seizuresduring awake and sleep.

Method: Thirty-six children (27 girls, 9 boys) aged 4–13 years withabsence epilepsy had routine 21-channel EEGs performed according tothe international 10–20 system. All children had both sleep and awake re-codring including HV and IPS. The average length of EEG recording was60 minnutes (between 40 and 90 minutes). All recorded absence seizureswere reviewed by two epileptologists. Electroclinical found during theGWS discharges in sleep were compared to the electroclinical features ofthe patient's awake absence seizures.

Result: 176 short paroxysms of GSW<2sec (113 spontaneous and 63during HV), and 222 long paroxysms of GSW lasting 3–35 seconds (132spontaneous and 90 during HV, respectively) were recorded. IPS pro-voked PPR in 10 patients (28%). During sleep 477 short and 193 longparoxysms of GWS were recorded, respectively. Interictal focal epilepti-form abnormality was noted in 9 patients (25%) during awake and in 16

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(44%) patients during sleep. Bifrontal onset of absence was revealed in 6,left frontal in 2 and right frontal in 5 patients. A clinical sign was seen in10 (28%) patients during sleep (staring look, blinking, eyelid and browjerks).

Conclusion: Short GSW < 2 sec were mainly recorded during sleep,while longer GSW paroxysms were presented during awake registration.Interictal focal abnormality was frequently seen during sleep. Either bi-frontal or unilateral frontal onset of absence was found in 1/3 of patients.

p784EPILEPSY OF INFANCY WITH MIGRATING FOCALSEIZURES- EXPANDING THE PHENOTYPE ANDEXPLORING THE AETIOLOGYA. Mctague*, R. Kneen�, M. Kurian�, R. Appleton�, andH. Cross**UCL-Institute of Child Health, London, UK; �Alder HeyChildren's NHS Foundation Trust, Liverpool, UK; and �UCL-Institute of Child Health, London, UK

Purpose: Epilepsy of infancy with migrating focal seizures, previouslyknown as migrating partial seizures of infancy, is a rare early infantileepileptic encephalopathy (EIEE). We describe novel clinical, MRI andEEG features and discuss the relationship of this disorder to other EIEEphenotypes .

Method: Eighteen cases were reviewed; 14 referred via the British Pae-diatric National Surveillance Unit (BPNSU) Study (a monthly survey ofconsultants in Paediatric Neurology in the UK and Republic of Irelandundertaken between April 2008 and April 2010) and 4 by personal com-munication. Data were collected using anonymised questionnaires.

Result: We present the findings from our cohort of 18 patients. Newclinical features included: severe gut dysmotility (N=3) and a movementdisorder (N=3). Previously unreported EEG findings include hypsar-rhythmia in 4(associated with infantile spasms in 3) and burst-suppres-sion in 3. Abnormal myelination on cerebral MRI was seen in 4 patientswith a particularly striking deficiency of myelination of the deep whitematter in 1 of these 4. MRS in 3 demonstrated decreased N-acetyl aspar-tate suggesting failure in brain maturation. One patient had putaminalatrophy on MRI and post-mortem examination. SCN1A testing in sevenpatients was negative. Molecular genetic investigation (using an earlyinfantile epileptic encephalopathy gene panel and whole exome sequenc-ing strategy) is currently underway.

Conclusion: Epilepsy of infancy with migrating focal seizures is an age-related electro-clinical syndrome which may evolve both into, and from,other EIEE syndromes including West syndrome. Further elucidation ofthe molecular genetic basis may confirm shared disease mechanismsbetween the different EIEE phenotypes.

p785ABERRANT FUNCTIONAL CONNECTIVITY BETWEENSENSORIMOTOR AND PREFRONTAL CORTEXREGIONS IN ROLANDIC EPILEPSYG. M. Overvliet, R. Besseling, J. Jansen, J. Vles, P. Hofman,A. Aldenkamp, and W. BackesKempenhaeghe, Heeze, The Netherlands

Purpose: Children with Rolandic epilepsy frequently show comorbidlanguage problems. It is unknown how epileptiform activity from the sen-sorimotor (Rolandic) area might influence distal language areas. Toinvestigate possible neuronal linking between the sensorimotor cortexand language mediating areas, functional connectivity networks werestudied by fMRI.

Method: 23 children with Rolandic epilepsy (age 11.4 € 2.0 years) and21 age and gender matched healthy controls (age 10.3 € 1.7 years) under-went testing of language using the CELF-4. Task functional MRI wasperformed using a covert word generation task, a text reading task and afinger tapping task. ROIs were used to assess laterality index distribu-tions of the activation for the word generation and reading task and to per-form a functional connectivity analysis based on correlation of ROIaveraged resting state fMRI time series.

Result: The lateralization index showed that both the word generationtask and reading task elicited bilateral activation with some predomi-nance for the left hemisphere. In comparison to controls, patients showeddecreased functional connectivity between the left sensorimotor cortexand the right inferior frontal cortex and increased connectivity betweenthe left anterior cingulated cortex and bilateral temporal regions.

Conclusion: The aberrant connections found indicate a disturbedinvolvement of prefrontal and temporal language areas in Rolandic epi-lepsy. In particular, the aberrant interhemispheric connection betweenthe left sensorimotor area and the right inferior frontal cortex suggests apathway through which epileptiform activity from Rolandic strip canadversely affect language function.

p786CLINICAL PROFILE OF PSYCHOGENIC NONEPILEP-TIC SEIZURES IN CHILDREN AND ADOLESCENTS: ASTUDY OF 37 CASESM. Gupta, Y. Patidar, G. A Khwaja, D. Chowdhury, A. Batra,and A. DasguptaG.B.Pant Hospital, New Delhi, India

Purpose: To study the clinical and video-EEG profile of pediatric andadolescent patients with Psychogenic Nonepileptic Seizures (PNES)

Method: All patients below 18 years of age with clinical suspicion ofPNES were included in the study. After history and clinical examination;all were confirmed by induction either during video-EEG monitoring orbedside. After proper disclosure of diagnosis, nonstructural psychother-apy and appropriate medications was given.

Result: Out of 37 patients, 24 (64.85%) were females and 13 (35.15%)were males. M:F ratio in age group <12 years was 3:1 whereas, in the 13–18 year group it was 1:1.8. The mean age was 14.7 years and mean dura-tion of illness was 13.7 months. 29 (78.38%) were students, while 8(21.62%) were school dropouts. 5 (13.5%) had coexisting epilepsy,whereas 32 (86.5%) had only PNES. Among 32 patients with only PNES17 (53.12%) were on antiepileptic drugs. Patients were divided into:Group A (motor attacks: 35.15%), and Group B (limp attacks: 64.85%).Common features were pre-ictal headache, resistant behaviour, ictal eyesclosure, partial responsiveness, teeth clenching, lying limp for variableduration, waxing-waning pattern, and asynchronous movements. Historyof emotional abuse was present in 11 cases (29.73%), physical and emo-tional abuse in 8 (21.62%) and physical and sexual abuse in 6 cases(16.2%).

Conclusion: PNES is common, but frequently underdiagnosed in pedi-atric and adolescent population. A high index of clinical suspicion andconfirmation by video-EEG is diagnostic. An early diagnosis, identifica-tion and counselling can improve their outcome and prevent unnecessaryusage of antiepileptic medications.

p787EPILEPSY AND THE IMMUNE SYSTEM ‘‘... IS THEREANTIBODY THERE?...’’S. Wright*, C. M. Jol-Van Der Zijde�, M. J. D. Van Tol�,P. Waters*, B. Lang*, O. F. Brouwer�, and A. Vincent*

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*University of Oxford, John Radcliffe Hospital, Oxford, UK;�Leiden University Medical Centre, Leiden, The Netherlands;and �University Medical Centre Groningen, Groningen, TheNetherlands

Purpose: Immune mechanisms are thought to be involved in the patho-logical disease process in a significant number of childhood and adultepileptic syndromes, and in other seizure related disorders (e.g. encepha-litis). Of particular interest is the occurence of highly specific autoanti-bodies to important neuronal proteins (VGKC-complex proteins,NMDAR, AMPAR, GABAbRs) in the blood and spinal fluid in some ofthese patients. The aim of this study is to examine the sera of newly diag-nosed paediatric epilepsy patients for the presence of specific neuronalautoantibodies.

Method: This Dutch cohort consists of 178 paediatric patients agedbetween 1 month and 16 years with newly diagnosed epilepsy. The seraare being tested for antibodies to the NMDA receptor, VGKC-complexand associated proteins (LGI1, CASPR2, contactin-2), GAD and glycinereceptor. The presence of antibodies are detected visually using antigenspecific cell-based assays (NMDAR, LGI1, CASPR2, contactin-2, gly-cine receptor), and the levels of antibodies against the VGKC-complexand GAD are quantitated by radioimmunoprecipitation assays.

Result: In total, 25/178 patients (14%) have been found to have a posi-tive antibody test so far. The most commonly found antibody is to theVGKC-complex.

Conclusion: Preliminary testing of a newly diagnosed paediatric epi-lepsy cohort has revealed a significant number of patients with poten-tially pathogenic neuronal autoantibodies in the serum. Further work willinclude completion of testing for antibodies to the CNS antigensdescribed, a coded comparison with age-matched controls, a search fornovel antigenic targets and the correlation of patient clinical features withthe presence of a positive antibody.


p788PREVALENCE AND ASSOCIATIONS OF ADHD IN RO-LANDIC EPILEPSYB. Mukhtyar*, A. Smith*, T. Clarke�, N. Dorta�, and D. K. Pal**King's College London, London, UK; and �ColumbiaUniversity, New York, NY, USA

Purpose: Children with epilepsy have elevated levels of ADHD andpsychiatric symptomatology, although the relative profiles for rolandicepilepsy (RE) are not well documented. We assessed prevalence ofADHD and psychiatric symptomatology in RE, and tested the hypothesisof a specific association with hyperactive-impulsive subtype.

Method: We prospectively assessed ADHD symptoms among 42 unse-lected participants in a US genetic study of RE. We used the AttentionDisorders Evaluation Scale (ADDES), Brief Rating of Executive Func-tion (BRIEF), and Child Behavior Checklist (CBCL). We calculatedstandardised scores.

Result: Parents rated 19% of RE children symptomatic for ADHD, pre-dominantly combined type using the ADDES; we obtained coherentresults from BRIEF and CBCL. Three quarters of children symptomaticfor ADHD were rated in the symptomatic range for one or more psychiat-ric or competency problems, a seven-fold increased risk for DSM disor-ders compare to RE children without ADHD symptoms. These weremainly in internalising behaviours, somatic symptoms and attentionproblems.

Conclusion: ADHD symptoms are as common in RE as in other epi-lepsy types but there is no evidence for a specific association with anADHD subtype. The presence of ADHD symptoms is a marker for psy-chiatric disturbance regardless of epilepsy status. Physicians managingchildren with ADHD should screen for and assess behavioural, emotionaland psychiatric problems in children with new-onset epilepsy, and bearin mind that ADHD symptoms often herald broader psychopathology andcompetency issues.

p789JUVENILE MYOCLONIC EPILEPSY: A FAMILYSTUDYE. Cvetkovska, I. Kuzmanovski, T. Cepreganova Cangovska,D. P. Cvetkovska, and B. BoskovskiUniversity Clinic of Neurology, Skopje, Macedonia

Purpose: To evaluate clinical features of probands with JME andaffected members of their families.

Method: Clinical and genealogic data were collected from 12 probandswith JME and family members with history of seizures.

Result: Mean number of affected individuals per family was three. JMEprobands group consisted of 3 males and 9 females, age of seizure onsetbeing 8 - 18 years (mean 13, 6 y.). All had myoclonic jerks and general-ized tonic-clonic seizures (GTCS); absences were reported in 41%. 22relatives were found to have seizures, 13 females and 9 males, age atonset 7–39 years (mean 16, 7 y). In half families, JME was the only clini-cal feature, in others there were members with other forms of IGE.Totally 13 family members had JME, epilepsy with GTCS only was diag-nosed in 2, juvenile absence epilepsy in 2, adult onset myoclonic epilepsyin 1 and indeterminate type of epilepsy remained in 4 of affected individ-uals. In two multi-generation families, phenomenon of possible geneticanticipation was observed, i.e. the onset of disease had a tendency todecrease in age which each successive generation.

Conclusion: Substantial number of families broadly share the same phe-notype, but the others appear to have a range of different phenotypes.Roughly uniform age-at-onset was found in majority of families,although phenomenon of possible genetic anticipation was observed intwo.

p790LEVETIRACETAM MONOTHERAPY IN PATIENTSWITH JUVENILE MYOCLONIC EPILEPSYJ. KimNeurology, Hallym University Sacred Heart Hospital, Anyang,Korea

Purpose: Although valproate is a well-known first-line antiepilepticdrug in juvenile myoclonic epilepsy (JME), valproate has a lot of tolera-bility problems, especially in adolescence and women of childbearingpotential. Levetiracetam (LEV) has been reported as one of alternativefirst-line antiepileptic drugs in JME. We want to describe our experiencewith LEV monotherapy in young women.

Method: We reviewed medical records of patients with JME treatedwith LEV monotherapy.

Result: Among 7 patients [all females, mean age 21.3 years (18~27)],LEV was initial monotherapy in 2, second monotherapy in 4, and thirdmonotherapy in 1 patient. Four patients became seizure free and 3patients had only myoclonic jerks. No patient had significant adverseevents. All patients were subscribed as once-a-day schedule and the aver-age daily doses were 678.5 mg (500~1000 mg). Minimum follow upduration was 18 months.

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Conclusion: Our report demonstrates good efficacy and tolerability ofLEV in JME patients and supports that LEV could be a first-line therapyin JME, especially in women of childbearing potential.

p791TEMPORAL LOBE EPILEPSYT. Chepreganova-Changovska, E. Cvetkovska, I. Kuzmanovski,and B. BoshkovskiUniversity Clinic of Neurology, Skopje, Macedonia

Purpose: Temporal epilepsy is the most frequent form of partial orlocalized epilepsy and it is considered that is responsible for 60% of thepatients with epilepsy. There are two types of temporal epilepsy: the for-mer which affects the medial and internal structures of temporal lobe –medial temporal epilepsy, and the latter, which involves the outer struc-tures of temporal lobe – neocortical temporal epilepsy. The most frequentform of these two types of temporal epilepsy is medial temporal epilepsy.

Method: MRI and EEG findings were evaluated in 30 patients with thediagnosis of TLE (18 females and 12 males, F:M ratio = 1.5), aged from16 to 57 years, admitted at the Clinic of Neurology, the Unit for Epilepsy,within the period 2009 to 2010.

Result: Pathological finding was registered in 75% of patients, 25% hadnormal finding on MRI. In 13 patients hippocampal sclerosis was found.EEG finding was registered for focal activity in 72% of the patients, witha positive finding for hippocampal sclerosis on the same side. Dischargesof the peak-wave complex on the other side of the HS also were regis-tered in two (18%) patients. Dual pathology (+HS) was registered in 2patients (15.3%).

Conclusion: Epileptogenic focus in temporal epilepsies should be theinitial ground for its further regular managing, and in some cases for fur-ther pre-surgical evaluation.

p792BATHING EPILEPSY TRIGGERED BY EMERSIONFROM WATER AND TOWEL WRAPPING: A CASEWITH ICTAL VIDEO-ELECTROENCEPHALO-GRAPHIC RECORDINGC. Aguiar*, R. Sousa*, A. Maia*, D. Alves�, and R. Rego�

*Hospital de S¼o Jo¼o, Porto, Portugal; and �Servico deNeurofisiologia, Porto, Portugal

Purpose: Bathing epilepsy is a rare form of reflex epilepsy. In previ-ously reported cases, onset is during early childhood and seizures are usu-ally triggered by immersion in water. Prognosis is favourable andpharmacological treatment is seldom required. We describe a case fittingthis diagnosis but with distinct and peculiar features.

Method: Clinical case report

Result: 3-year old caucasian male, with normal psychomotor develop-ment. The parents reported recurrent episodes of vomiting and drowsi-ness when taken out of the bath, since the neonatal period. At the age of 2and a half, the semiology of these bath-related episodes changed, includ-ing pallor, loss of contact, hypotonia, and oral automatisms. The onlyreproducible (and systematic) triggers were emersion from water fol-lowed by towel wrapping. Video-EEG recordings confirmed this semiol-ogy and showed left frontotemporal ictal patterns. Interictal EEG, brainMRI, and EKG-Holter were normal. The child was started on carbamaze-pine. During the short follow-up period, response to this drug seemsfavourable, albeit incomplete.

Conclusion: We believe that this video-EEG documented case of bath-ing epilepsy presents peculiar features worth reporting, including a neo-natal onset (with pure autonomic reflex seizures), and triggering by thevery specific sequence of emersion from water followed by contact witha towel.

p793CLINICAL HETEROGENEITY IN FAMILIAL PARTIALEPILEPSY WITH AUDITORY FEATURES NEGATIVEFOR LGI1 AND WITH MATRILINEAL INHERITANCEC. Leta*, F. Bisulli*, F. Pittau�, L. Licchetta�, C. Stipa*,I. Naldi*, L. Alvisi§, and P. Tinuper§

*IRCCS Istituto delle Scienze Neurologiche di Bologna,Universit di Bologna, Bologna, Italy; �Montreal NeurologicalInstitute and Hospital, McGill University, Montreal, QC,Canada; �Istituto delle Scienze Neurologiche, Universit diBologna, Bologna, Italy; and §IRCCS Istituto delle ScienzeNeurologiche, Bologna, Italy

Purpose: Autosomal Dominant Partial Epilepsy with Auditory Features(ADPEAF) is a benign epileptic syndrome characterized by focal sei-zures with typical auditory auras and/or other symptoms of lateral tempo-ral origin, often followed by secondary generalization. LGI1 mutationshave been identified in about 50% of ADPEAF families and genetic het-erogeneity has been widely documented. We describe a family with AD-PEAF presenting with atypical clinical features, expanding thephenotype of the syndrome.

Method: We studied a family of four generations, including 53 individ-uals, of which seven with epilepsy and six with febrile seizures (FS). Allaffected members have been clinically investigated and screened forLGI1 mutations.

Result: The proband and her daugther presented partial epilepsy withauditory features, associated in the proband with drug-resistance, myoc-lonus, intentional tremor, sensorineural hearing loss and generalizedspike and waves on EEG recording. Two members in the matrilineal lineexperienced generalized seizures in childhood and three have focal epi-lepsy. One of them has mental retardation (MR) and died for SUDEP.Genetic analysis failed to disclose mutations for LGI1 in all screenedmembers.

Conclusion: This family differs from the ‘‘classical’’ ADPEAF syn-drome, in several peculiar clinical features: presence of IGE (idiopathicgeneralized epilepsy) trait in the proband, high frequency of FS, seizurescharacterized by variable phenotype in different members, possiblematrilineal inheritance of epilepsy, mental retardation. This phenotypicheterogeneity of the syndrome supports the evidence that gene other thanLGI1 are responsible for ADPEAF.

p794RARE COPY NUMBER VARIANTS IN LENNOX-GAS-TAUT-LIKE EPILEPSYC. Lund*, E. Brodtkorb�, O. Røsby�, and K. K. Selmer�

*Oslo University Hospital, Bærum Postterminal, Norway;�Trondheim University Hospital, Trondheim, Norway; and�Oslo University Hospital, Oslo, Norway

Purpose: Objectives: Lennox-Gastaut syndrome (LGS) is characterizedby multiple seizure types, cognitive impairment and specific EEG find-ings. To explore possible genetic predispositions, we have searched forcopy number variants (CNVs).

Method: LGS-like epilepsy was broadly defined as at least three differ-ent types of generalized seizures, including tonic seizures or the combina-tion of atonic seizures and atypical absence, learning disability, treatmentresistance and bilateral epileptiform discharges. Whole-genome arraycomparative genomic hybridization (aCGH) was performed in 21 con-secutive adult patients.

Results: Eight patients (38%) carried one or more rare CNVs. All weremen; two had single duplications, four had single deletions, one had aduplication and a deletion and one had multiple duplications/deletions.

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Average CNV size was 997 kb (0.05 kb–4.7 Mb). Three patients hadCNVs and clinical pictures matching known genetic syndromes; 22q13.3deletion, 2q23.1 deletion, and MECP2 duplication.

Conclusions: Previously, syndromic disorders were identified by theirclinical features. The patients in this study were lacking sufficient spe-cific history and features to suggest a genetic or non-genetic cause. How-ever, they were diagnosed with genetic syndromes as a result of genetictesting combined with a consecutive phenotype evaluation. Our studydemonstrates the usefulness in identifying the genotype in order to shedlight on the phenotype and reveal the etiology in epileptic disorders.

p795CLINICAL AND VIDEO-POLYGRAPHIC FEATURES OF‘‘SENILE PROGRESSIVE MYOCLONIC EPILEPSY’’: ADISTINCTIVE PROGRESSIVE MYOCLONIC EPILEPSYOF ADULT DOWN PATIENTSG. D’Orsi*, M. Trivisano�, M. G. Pascarella�, F. Pacillo*,E. Carapelle�, C. Luisi�, M. T. Di Claudio�, T. Francavilla�, A.La Neve§, V. Demaio–, M. Minervini–, and L. M. Specchio�

*Epilepsy Center, Clinic of Nervous System Diseases, Universityof Foggia, Riuniti Hospital. Foggia, Italy; �Foggia, Italy; �BariPolyclinic, Bari; §Polyclinic of Bari, Bari; and –NeurologicalUnit, Bisceglie, Italy

Purpose: Little is known about the clinical and polygraphic features ofSenile Myoclonic Epilepsy, a myoclonic epilepsy associated withdementia in adult Down patients. This study investigates the clinical andvideo-polygraphic features of 8 patients with Senile Myoclonic Epilepsy,focusing on the evolutive aspects of myoclonic epilepsy and dementia.

Method: Four women and four men, affected by Down syndrome, 51–70 years old (median 54.6 years), were submitted to clinical and neuro-physiological (polygraphic recording with jerk-locked back-averaging)investigations. The mean follow-up was 5 years from dementia onset.

Result: Three clinical-polygraphic phases emerged. The first phase wascharacterized by a late onset (> 50 yrs) of a slowly progressive cognitivedecline associated with generalized epileptiform abnormalities duringsleep. After about one year, there was a gradual onset of second phasewith a worsening of cognitive disorders associated with myoclonic sei-zures, usually occurred on awakening, and/or occasional generalizedtonic-clonic seizures. Polygraphic features showed generalized fastspike-waves with bilateral myoclonic jerks, especially at awakenings.Finally, a third phase followed with dementia, ataxia, myoclonus andphotosensitivity with rhythmic myoclonic jerks at a frequency of 12–24Hz. Burst-locked electroencephalographic averaging generated a contro-lateral positive-negative central transient preceding the myoclonus EMGdischarge by 20–24 ms, compatible with a cortical origin.

Conclusion: Our patients showed a distinctive clinical - polygraphicpicture (myoclonus, epileptic seizures, signs of neurological deteriora-tion, particularly dementia and ataxia), suggestive of a progressive myo-clonic epilepsy, that we propose to name ‘‘senile progressive myoclonicepilepsy’’. Molecular studies are needed to characterize this syndromefrom the physiopathological point of view.

p796IDIOPATHIC OCCIPITAL LOBE EPILEPSY ANDABSENCE EPILEPSY IN THE SAME PATIENT?H. P. Grebe, and A. FerreiraCentro Hospitalar de Entre Douro e Vouga, Hospital S¼oSebasti¼o, Santa Maria da Feira, Portugal

Purpose: Gastaut type occipital lobe epilepsy of infancy is a rare condi-tion. Seizures typically consist of visual hallucinations, blindness or both,with or without motor manifestations. In some cases, additional atypicalabsence seizures have been described. On the other hand, aura phenom-

ena have been described in idiopathic generalized epilepsies, althoughthey usually were not visual.

Method: We present the case of a girl, who developed, at 5 years of age,brief episodes of behavioral arrest with blinking, which were preceded oraccompanied by visual phenomena (micropsy and/or blindness). On atleast one occasion she had visual symptoms without subsequent loss ofconscience. The neurological exam was normal.

Result: The EEG showed bursts of generalized 3Hz spike-slow wavecomplexes, at times starting in the right posterior region, OIRDA, occipi-tal sharp waves with right predominance and a fotoparoxysmal response.Magnetic resonance imaging was normal. On 24 hour-V�deo-EEG, onebrief seizure was recorded, which consisted of repetitive blinking, associ-ated to rhythmic 4Hz sharp waves in the occipital regions. Valproic acidled to seizure control at a dosage of 740mg/day.

Conclusion: We present this case as an unusual example of a differentialdiagnosis to be made between an association of a focal idiopathic epi-lepsy with a generalized idiopathic epilepsy versus a generalized epilepsywith focal aspects, clinically and neurophysiologically. Prognostic andtherapeutic implications of this distinction will be discussed.


p797DOES PHOTOPAROXYSMAL EEG RESPONSE PRE-DICT SEIZURES CONTROL IN PATIENTS WITH JUVE-NILE MYOCLONIC EPILEPSY?M. P. Borkovic, and J. B. JancicClinic of Neurology and Psychiatry for Children and Youth,Belgrade, Serbia

Purpose: To evaluate does photoparoxysmal EEG response (PPR) pre-dicts seizures control in patients with juvenile myoclonic epilepsy (JME).

Method: Retrospectively we analyzed 109 patients with JME diagnosedand treated in period of 2002–2010 at Clinic of Neurology and Psychiatryfor Children and Youth. PPR was defined by Waltz criteria during stan-dard intermittent photic stimulation (IPS), and classified in four types.

Result: We analyzed 109 patients with JME aged 12 - 39 years, meanold 20.1 years (SD -5.2 years), 65 (59.6%) females and 44 (40.4%) males.PPR was detected in 50 patients (29 females, 21 males). Waltz type IV(PPRs) was detected in 39 (23 females), and type III in 11 (6 females)patients. Forty one patients (82%) were photosensitive at flash frequen-cies between 10 and 30. In patients with PPR three patients had poor sei-zure control (six in group without PPR).

Conclusion: PPR is most frequent in JME females. PPR type IV is mostfrequent in both genders. There is no difference in seizure controlbetween patients with and without PPR. True prevalence of PPR in JMEis difficult to evaluate because of the different definitions of PPR and thedifferent protocols used for IPS .

p798NOCTURNAL FRONTAL LOBE EPILEPSY AND PARA-SOMNIAS DIFFERENTIAL DIAGNOSIS: ACCURACYOF TWO DIFFERENT CLINICAL DIAGNOSTIC TOOLSM. Broli*, F. Bisulli�, L. Di Vito�, C. Leta�, B. Mostacci�,I. Naldi�, P. Tinuper�, and L. Vignatelli�

*IRCCS, Istituto delle Scienze Neurologiche di Bologna,Bologna, Italy; �IRCCS Istituto delle Scienze Neurologiche diBologna, Universit di Bologna, Bologna, Italy; and �City ofBologna Local Health Trust, Bologna

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Purpose: To explore the diagnostic performance of two different toolsfor the nocturnal frontal lobe epilepsy (NFLE) and parasomnias differen-tial diagnosis: Frontal Lobe Epilepsy and Parasomnias Scale (FLEPscale) and structured interview for nocturnal frontal lobe epilepsy (SIN-FLE). In fact the standard criteria for nocturnal episodes are unreliable orare still lacking.

Method: 35 subjects with suspected NFLE or parasomnias, have beenreferred to our Sleep Epilepsy Center during the last three years. Accord-ing to anamnestic, clinical and instrumental (EEG, home-video andvideo-EEG polysomnography, VEPSG) data 19 subjects were diagnosedas NFLE, 8 as parasomnias and 8 as uncertain diagnosis. After at least sixmonths follow-up, all patients were re-evaluated through the FLEP scaleand SINFLE, telephonically administered by a neurologist blinded to theinitial diagnosis.

Result: The FLEP data were in agreement with the first diagnosis for15/19 NFLE and for 5/8 parasomnias; the SINFLE data were in agree-ment with the first diagnosis for 12/19 NFLE and for 6/8 parasomnias;both tools agreed with final diagnosis in judging uncertain patients.

Conclusion: FLEP scale and SINFLE showed a similar diagnostic per-formance in the NFLE and parasomnias cases, so an assessment of thelikelihood of epilepsy may be made at the initial consultation, even whenthe clinician has limited experience with these conditions, suggesting oravoiding a VEPSG.

p799FOCAL EEG ABNORMALITIES IN CHILDHOODABSENCE EPILEPSY – ANY PROGNOSTIC VALUE?M. Mazurkiewicz-Beldzinska, A. Matheisel, and M. SzmudaMedical University of Gdansk, Gdansk, Poland

Purpose: Childhood Absence Epilepsy is an Idiopathic GeneralizedEpilepsy (IGE) syndrome characterized by typical absence seizures(TAS). In last years it becomes more and more evident that focal EEGchanges can be detected in patients with CAE. In order to estimate thefrequency of this changes and their possible prognostic value presentstudy was undertaken.

Method: Patients with childhood absence epilepsy (CAE) who werehospitalized or consulted at Dept. of Developmental Neurology between2000 and 2011 were included in the study and followed prospectively.All patients underwent video-eeg monitoring at regular interwals (approx6 months).

Result: 197 patients who fulfilled criteria for CAE were included in thestudy. In 17% of them we found interictal focal epileptiform discharges,and in 37% intermittent temporal slow waves. We found significant cor-relation between presence of interictal focal epileptiform discharges andlong term prognosis, but did not find the correlation between worse prog-nosis and presence of temporal interictal slow wave activity. Howeverthe strongest correlation was found between the absence of interictalchanges and seizure freedom. We also did not found the associationbetween the presence of interictal focal abnormalities and performancein cognitive tasks.

Conclusion: The value of focal interictal EEG abnormalities should notbe overestimated according to prognosis and cognitive performance inchildren with CAE.

p800CLINICAL, GENETIC, AND EEG FEATURES OF TURK-ISH PROGRESSIVE MYOCLONIC EPILEPSYPATIENTSO. E. Ore*, N. Bebek�, F. N. Tuncer�, O. Ozdemir�, B. Baykan�,C. Gurses�, S. U. Iseri�, U. Ozbek�, and A. Gokyıgıt�

*Ozel Memorial Hizmet Hospital, Istanbul, Turkey; and�Istanbul University Istanbul Medical Fakulty, Istanbul, Turkey

Purpose: Progressive myoclonic epilepsy (PME) is a rare and heteroge-neous syndrome with various genetic etiologies. Therefore genetic stud-ies carry an important role in the diagnosis. However the underlyingmechanism of this syndrome is not understood. We aimed to determinethe the clinical, genetic and EEG characteristics of Turkish PMEpatients.

Method: In this study, 16 (11 male, 5 female) consecutive PME patientswere investigated. Characteristics of disease progression and dependencyin daily life activities were evaluated. Nine of the PME patients belong tothree families, and the remaining 7 patients were sporadic. The mean ageof patients was 37€12 years (19–64) at the examination. The mean age atthe onset of illness was 15€5 years (3–21). The mean follow-up periodwas 11€6 years (range: 2–21).

Result: We noticed a slow clinical progression in 2/3 of the patientsinterestingly and observed that similar baseline EEG abnormalities werecontinuing on EEG follow ups after years, without severe and worseningimpairment of background activity. Seven patients showed photosensi-tivity, four of them were sensitive to lower stimulation frequencies.Genetic analysis showed variants in 3rd exon of EPM2A gene in 2 sub-jects and in 1st exon of NHLRC1 gene in one patient, which were notreported previously. None of the previously reported mutations weredetected in our cohort except known polymorphisms which do not causeaminoacid changes.

Conclusion: This study showed better prognosis than expected in Turk-ish familial and sporadic PME cases. Presence of new genetic variationscan be speculated as the main reason of this slow progression.

p801‘‘DELAYED’’ DIAGNOSIS OF COELIAC DISEASE INADULT PATIENTS WITH POSTERIOR PARTIAL EPI-LEPSY: SEARCHING FOR A POSSIBLE LINKS. Casciato, A. Morano, J. Fattouch, L. Lapenta, M. Fanella,M. Manfredi, C. Di Bonaventura, and A. T. GiallonardoPoliclinico Umberto I, Rome, Italy

Purpose: Coeliac disease (CD) is an immuno-mediated small boweldisease characterized by chronic inflammation in the small intestinewall in genetically susceptible population due to a permanent intoler-ance to gliadin. CD is characterized by malabsorption, intestinal mucosaatrophy and serological positivity to AGA, tTG, EMA antibodies. Avariety of extra-intestinal symptoms has been recently reported even inpatients without enteric manifestations. Several neurological complica-tions have also been described, including epilepsy, whose evolutionmight improve thanks to a prompt diagnosis of CD and adequate gluten-free diet.

Method: Our study retrospectively revised 21 subjects (17 females, 4males) with posterior partial epilepsy. EEG, brain MRI/CT scan, sero-logical tests for CD and duodenal biopsy have been collected, as wellas data about response to antiepileptic drugs treatment and gluten-freediet

Result: Diagnosis of epilepsy always preceded the detection of CD:serological tests for CD were positive in 17/21 patients; in the others duo-denal biopsy was performed and CD confirmed. 18/21 patients presentedwith common ictal symptoms (visual manifestations, dizziness, confu-sion); in 17/21 cases the EEG showed focal posterior abnormalities; in 4/21 FOS phenomenon was observed. The neuroimaging studies docu-mented occipital calcifications in 4/21 patients. Gluten-free diet led to areduction of seizure frequency in half of patients.

Conclusion: Posterior epilepsy and CD can coexist in adults. Posteriorseizures could raise suspicion of CD. These patients might be drug-resis-tant and present ‘‘specific’’ EEG pattern, but often an apparently normalbrain. The causal relationship between these two conditions remainsincompletely understood.

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p802AN EPILEPSY BEDSIDE DIAGNOSIS BY DOING LOGI-CAL TASK IN FORM AD HOC FULL-TEXT DATABASEOF WORKING KNOWLEDGEV. M. AndreevMoscow State Medical Stomatolgy University, Moscow, RussianFederation

Purpose: To test ad hoc full-text database by making diagnosis of epi-lepsy.

Method: The woman age 25 years has been myoclonic seizures, ataxia,amblyopia, and eye fundus macular cherry-red spot. A diagnostic processwas done logical task in form of text database of working knowledge. Alogical task is comparing one item with another and to find the coincidenceas logical intersection of a certain quality. One item was consisted fromprominent seizure of myoclonus and the related sign as macular cherry-red spot. This item belongs to the set of disorders taken from the Internet.Other items were consisted from signs as ataxia and amblyopia. The com-parison between three items was found the coincidence as sialidosis.

Result: We are diagnosed 113 patients, both genders, between aged 18and 56 years. The disorders were various paroxysmal disorders, rare epi-leptic syndromes, convulsive psychogenic status epilepticus, non epilep-tic staring spells, confusional attacks, dissociative fuges, epileptic staringspells, and sleep-related non-epileptic myoclonus. There has been aninety five per cent correct bedside diagnosis.

Conclusion: Diagnosing paroxysmal disorders by doing logical task inform ad hoc full-text database is making provable bedside diagnosis.

p803AUTOSOMAL RECESSIVE PARTIAL EPILEPSY WITHINTELLECTUAL DISABILITY (ARPEID) – A NOVELEPILEPSY SYNDROME?Z. Afawi*, J. Abu-Rachma�, S. Kivity�, I. Blatt§, and I. Helbig–

*Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv,Israel; �Shfaram, Israel; �Schneider Children's Medical Centerof Israel, Petach Tikva, Israel; §Sheba Medical Center, Tel Aviv,Israel; and –Kiel, Germany

Purpose: Recessive epilepsies constitute a major source of genetic mor-bidity in seizure disorders in the Middle East. Careful clinical characteri-sation and thorough description of the epilepsy syndromes are theprerequisite for successful gene discovery. The purpose of this study wasto describe the peculiar clinical features in two sisters from a consanguin-eous Arab family.

Method: A consanguineous Arab family with two affected sisters andone affected cousin were characterized clinically and electroencephalo-graphic and imaging data was reviewed.

Result: Both sisters presented with a similar phenotype, includingsevere primary developmental delay, muscular hypotonia and intellectualdisability. At the age of 3 years, both sisters developed a focal seizure dis-order with complex partial seizures and bitemporal discharges on theEEG. While seizures in one sister improved over time and were well-con-trolled at the time of the last consultation, the seizures remained refrac-tory in the other sister. An affected cousin presented with a much milderneurological phenotype. Hydrocephalus of possibly perinatal origin wasnoted, suggesting that the phenotype in the cousin may represent a pheno-copy.

Conclusion: Given the similar clinical features in both sisters, wehypothesize that the phenotype may represent a novel autosomal reces-sive epilepsy syndrome and we suggest the term Autosomal RecessivePartial Epilepsy with Intellectual Disability (ARPEID). Given the possi-

ble phenocopy in the affected cousin, this pedigree highlights the chal-lenges of careful phenotyping. Genetic discovery of the underlyinggenetic alteration using novel technologies such as Massive ParallelSequencing will provide the opportunity to unravel the underlyinggenetic alteration.

p804SLC2A1 MUTATIONS ARE CAUSE OF INFANTILEDRUG RESISTANT SEIZURES AND PAROXYSMALEXERCISE-INDUCED DYSKINESIAM. K. Jurek, D. Hoffman-Zacharska, M. Kruk, E. Szczepanik,M. Geremek, and A. FriedmanInstitute of Mother and Child, Warszawa, Poland

Purpose: Glucose transporter-1 deficiency syndrome is an autosomaldominat disorder caused by mutation in SLC2A1 gene in the majority ofpatients results in reduce glucose transport into the brain. Patients withGLUT1 deficiency syndrome represent wide clinical spectrum of symp-toms such as infantile drud-resistant seizures, developmental delay,microcephaly, spasticity and dystonia.

Our purpose was to establish whether SLC2A1 mutation are commonin patients with GLUT1 deficiency syndrome and comparison the clinicalpicture with the context of causative mutation.

Method: Genomic DNA was extracted from peripheral blood . StandardPCR amplification of SLC2A1 gene of all 10 exons was perform usingpreviously published primers. The coding regions of SLC2A1 weresequenced. For patients withoy point mutation the presence of gene'sdeletion/duplication was analysed by MLPA (SALSA MLPA P138-B1MRC Holland) additionally. Unreported new variant was verified in apanel of 200 control alleles.

Result: Mutation analysis was performed for all patients with GLUT1deficiency syndrome. We identified one already known mutationc.634C>T (p.R212C) in a patient with idiopathic generalized drug-resis-tant epilepsy and a novel variant c.275+3A>C in a patient with paroxys-mal exercise-induced dyskinesia. The new variant was not not found in100 normal control subjects.

Conclusion: Recognizing glucose transporter-1 deficiency syndrome isvery important, since the disorder can be treated with a ketogenic diet. Inmost cases the diet reduces the frequency of seizures and the severity ofthe movement disorder.

p805MAGNETOENCEPHALOGRAPHY FINDINGS IN TWOCASES OF IDIOPATHIC GENERALIZED EPILEPSIESS. Carrasco Garc�a De Le�n*, M. Gud�n Rodriguez-MagariÇos*, L. Burriel Lobo*, G. Niso Galan�, and F. MaestuUnturbe�

*Hospital General Universitario De Ciudad Real (Spain),Ciudad Real, Spain; and �Universidad Complutense De Madrid,Madrid, Spain

Purpose: Among others the three main syndromes of Idiopathic Gener-alized Epilepsies (IGE) consists of Juvenile myoclonic epilepsy (JME),juvenile absence epilepsy (JAE), and epilepsy with generalized tonic-clo-nic seizures on awakening. From a neurophysiological, neuropsychologi-cal and neuroimaging point of view these three entities have consistentlypointed out towards subtle abnormalities in frontal lobes (Santiago 2002,Roebling 2009). Using magnetoencephalography (MEG) we investigatedelectromagnetic sources of epileptic activity in 2 patients with IGE.

Method: We retrospectively compared MEG and EEG. Using 306-channel helmet-shaped MEG with a sampling rate of 600 Hz. Singledipole analysis assuming a spherical head model was performed forlocalization.

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Result: Case 1: 25 years old man with JME diagnosis by the age of 16years. He was on remission for 3 years. MRI was normal. He showed anEEG recording normal. MEG detected spike and spike-wave localised atleft fronto-parietal region. Case 2: 25 years old female with JME diagno-sis by the age of 12 years. She was on remission for 4 years. MRI was nor-mal. EEG recording: spikes and slow waves of polyspike, generalized,bilaterally symmetrical, 4 to 6 Hz. MEG analysis: polyspike generalizedwith predominance bilateral fronto-parietal lobes, the spikes were morefrequent than in EEG

Conclusion: In these two cases MEG has a higher sensitivity and spatialresolution than scalp EEG, therefore MEG could localize frontal epilepticsource predominance, not clearly revealed by scalp EEG. Implication ofthe frontal and parietal areas it is suggested by MEG data, as the neuro-psychological, neuroimaging and neurophysiology previous reports havepreviously pointed out.

p806OUTCOME AND PROGNOSTIC FEATURES IN SCN1APOSITIVE DRAVET SYNDROME FROM INFANCY TOADULT LIFEA. Brunklaus, R. Ellis, E. Reavey, G. Forbes, and S. M. ZuberiRoyal Hospital for Sick Children, Glasgow, UK

Purpose: Dravet syndrome is a severe infantile onset epileptic encepha-lopathy associated with mutations in the SCN1A gene encoding the alphasubunit of the voltage gated sodium channel Nav1.1. To date no largestudies have systematically examined the outcome and prognostic fea-tures of the disease.

Method: We prospectively collected data on 241 SCN1A mutation posi-tive Dravet syndrome cases aged 1 to 42 years over a five year period.From structured referral data we examined a range of clinical characteris-tics including epilepsy phenotype, seizure precipitants, vaccination his-tory, EEG data, imaging studies, response to treatment, mutation classand neuro-cognitive sequelae. Predictors of developmental outcome weredetermined by logistic regression.

Result: There was a significant increase in the degree of learning dis-ability seen in the older age groups (X2=184.45, df=24, p<0.001). Withadvancing age we similarly observed a significant increase in autistic fea-tures (X2=39.53, df=6, p<0.001), behaviour problems (X2=54.05, df=6,p<0.001) and acquired motor disorder (X2=37.19, df=6, p<0.001). Thepresence of status epilepticus (OR=3.1; CI=1.5–6.3; p=0.003), motor dis-order (OR=3.3; CI=1.7–6.4; p<0.001), interictal EEG abnormalities inthe first year of life (OR=5.7; CI=1.9–16.8; p=0.002) and early cognitiveimpairment (OR=0.9; CI=0.94–0.99; p=0.009), each predicted a worsedevelopmental outcome. No significant effect was seen for seizure pre-cipitants, vaccination history, MRI abnormalities or mutation class (trun-cating vs. missense).

Conclusion: The identification of factors influencing prognosis bothaids counselling and encourages early, syndrome specific therapy.Prevention of status epilepticus with regular medication and emer-gency protocols is important and may influence developmentaloutcome.


p807ESES (CSWSS) IN A MIDDLE-AGED MANM. Arvio, O. Sauna-Aho, and T. NyrkeLahti, Finland

Purpose: ESES (epilepsy with electrical status during slow-wave sleep)is a childhood onset electroclinical syndrome. We found no earlierdescription of middle-age onset ESES.

Method: The first author has followed the patient (born 1955) since1981. EEG recordings (N=7) were evaluated according to the intensity ofdischarges. The Wechsler intelligence test (WAISS, N=4) served inassessing the developmental profile.

Result: At the age of 8 months the patient was diagnosed as havingcerebral palsy and epilepsy. He learned to speak fluently and walk withthe help of a walking stick. He had mild intellectual disability. BrainMRI showed an almost missing right hemisphere with slight cortexalong the skull; also the left thalamus was destroyed. Follow-up 1999:Yearly, the patient had 1 or 2 facial jerks. EEG showed left parietal foci.AED: phenytoin and clonazepam. 2003: The patient was seizure-free;but he slept a lot and had become apathetic and walking difficultieswere obvious. The patient could not live alone anymore. 2005: Thepatient was aggressive and restless and kept on changing posture contin-uously. EEG showed ESES. AED: topiramate and phenytoin. 2006: Thepatient had several ‘‘dog-seizures’’ (panting like a dog and walking,tachykardia, sweating). 2009: Clobazam was started soon after that alldementia, psychotic and motor symptoms disappeared. 2012: Thepatient is seizure free and lives alone. EEG shows left parietal foci.AED: topiramate and clobazam.

Conclusion: ESES is worth keeping in mind for an adult patient withstructural brain abnormality and showing psychotic behavior and globalfunctional decline.

p808CAN NEONATAL ELECTROCLINICAL FINDINGSGUIDE TOWARDS AN EARLY DIAGNOSIS OF NEONA-TAL ENCEPHALOPATHY? A CASE REPORTB. Scelsa*, A. Peron*, L. Spaccini*, P. Introvini*, S. M. Bova*,R. Ciccone�, F. Novara�, O. Zuffardi�, and M. Mastrangelo**V. Buzzi Children's Hospital, Milano, Italy; and �Universit DiPavia, Pavia, Italy

Purpose: STXBP1 and SPTAN1 mutations are increasingly recognizedas responsible of early infantile epileptic encephalopathies with an EEGpattern ranging from discontinuous to burst-suppression. The purpose ofthis case report is to emphasize the possibility that a condition of enceph-alopathy, associated to a peculiar EEG pattern can, be representative ofspecific genetic early- onset epileptic encephalopathies, despite theabsence of epileptic seizures in the first month of life.

Method: We describe a female born after a pregnancy characterized bypolidramnios. Mild dysmorphic features, a severe swallowing defect andhypotonia were detected after birth.

Result: Protracted video-EEG recordings in the neonatal period dis-played an EEG pattern ranging from discontinuous to burst-suppression.MRI and metabolic investigations were unrevealing. At 2 months of lifeshe developed West syndrome, rapidly controlled after Vigabatrin treat-ment. The EEG improved before the end of the first year of life to anunspecific slowing of background activity without epileptic abnormali-ties. Significant improvement of swallowing was apparent after 6 monthsof life, permitting an oral nutrition. The psychomotor developmentresulted severely affected. The interaction was limited and the languageabsent. Rotatory nystagmus was observed. Array-CGH detected a denovo deletion of 2.4 Mb in 9q34.11 involving both STXBP1 andSPTAN1 genes.

Conclusion: Specific molecular genetic investigations should beincluded in the diagnostic work up of encephalopathic neonates present-ing with a peculiar pathological EEG pattern (from severely discontinu-ous to burst-suppression) even in the absence of epileptic seizures.

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p809NEUROLOGICAL ACPECTS OF DIALYSIS PATIENTSS. M. VujisicClinical Centre of Montenegro, Podgorica, Montenegro

Purpose: Metabolic encephalopathies are defined as any patologicalprocess that damages the methabolism of the brain in significant matterand inevitably alter level of consciousness.

Cognitive and emotional functions are amoung most complex brainactivities, and therefore are most sensitive to toxic product retention andsecondary metabolic changes.

Method: Group of 36 patients who were on hemodyalises were exam-ined. All of them were devided into two groups, group with normal, andgroup with abnormal EEG findings.

All patients underwent neuropsychology and MMSE examination.Test achievements were scored as 25 and more for normal, and 24 or lessfor abnormal results.

Result: In patients with abnormal results, who had MMSE done, regard-less the changes found in EEG, no statistically significant differenceswere found among the group. Number of patients who had score 25 ormore was the same compared with the number of patients who had score24 or less (8 patients).

In the first group with normal EEG, number of patients who had score25 and more was 18 (90%), compared with 2 patients who had score 24or less (10%).

Comparing the results for doing MMSE, statistically significant dif-ference was found among patients with normal EEG findings and patientswith pathological EEG findings.

Conclusion: Celebrovascular complications in these patients are ampli-fied and lead to cognitive disfunction, that are subcortical by nature.These findings are in the corelation with findings of the others who stud-ied the same pathology (Roman CG, 2003).

p810NEUROPSYCHOLOGICAL ASPECTS OF DIALYSISPATIENTSD. B. Milikic, L. B. Radulovic, S. M. Vujisic, and S. VujovicClinical centre of Montenegro, Podgorica, Montenegro

Purpose: Influence of toxic renal products on cognitive function inpatients on dialysis. Metabolic encephalopathies are defined as any path-ological process that damages the metabolism of the brain in significantmatter and inevitably alter level of consciousness.

Method: Group of 36 patients who were on hemodialysis were exam-ined. All of them were devided into two groups, group with normal andgroup with abnormal EEG findings. All patients underwent neuropsychi-atry and MMSE examination. Test achievements were scored as 25 andmore for normal, and 24 or less for abnormal result.

Result: In patients with abnormal results, who had MMSE done, re-gardelees the changes found in EEG, no statistically significant diferen-cess were found amoung the group. Number of patients who had score 25or more was the same compared with the number of patients who hadscore 24 or less (8 patients). In the first group with normal EEG, numberof patients who had score 25 and more was 18 (90%), compared with 2patients who had score 24 or less (10%) Comparing the results founddoing MMSE, stastistically significant diference was found amoungpatients with normal EEG findings and patients with patological EEGfindings.

Conclusion: Cerebrovascular complications in these patients are ampli-fied and lead to cognitive disfunction, that are subcortical by nature.These findings are in the correlation with findings of the others who stud-ied the same pathology (Roman CG, 2003).

p811EEG EVOLUTION IN CHILDREN WITH WEST SYN-DROMED. M. Nikolic*, N. Dimitrijevic�, D. Bogicevic�, V. Mitic�,B. P. Medjo�, S. Puric�, and I. Milovanovic**Belgrade University Medical School, Belgrade, Serbia; and�University Children's Hospital Belgrade, Belgrade, Serbia

Purpose: West syndrome (WS) is ‘‘catastrophic’’ epileptic encephalopa-thy with poor prognosis. The aim of the study was to determine the mostfrequent EEG pattern in patients with WS at the disease onset and duringtwo year follow-up period.

Method: Study group comprised 81 patients with WS whose EEG per-formed initially and after 3, 6, 12 and 24 months was analyzed.

Result: In 67.9% of patients initial EEG showed hypsarrhythmic pattern,in 19.8% modified hypsarrhythmia, in 4.9% ‘‘burst suppression’’ pattern,in 4.9% focal and in 2.5% multifocal EEG findings. After 3 monthsimprovement was observed in 56.2% of patients, unchanged findings in34.2%, deterioration in 9.6% (p<0.01). The best outcome was found inpatients with initial hypsarrhythmic pattern (63.8%) and somewhat worsein those with modified hypsarrhythmia (50%). Patients with ‘‘burst sup-pression’’ pattern and those with focal and/or multifocal EEG changes hadthe same or worse findings at all later check-ups. Trend of improvementwas continued at later follow-ups: 6 (48.1%), 12 (55.4%) and 24 months(37.1%), while unchanged EEG findings were found in 44.4%, 36.5% and53.2% of patients respectively. Worst EEG findings were recorded in7.4%, 8.1%, and 37.1% of patients after 6, 12 and 24 months respectively.

Conclusion: Stabilization of EEG 3 months after disease onset wasfavourable indicator and has its’ clinical significance for seizure controland psychomotor development.

p812SEVERE PATTERN-SENSITIVITY IN A GIRL WITHDRAVET SYNDROME, DUE TO MICRODELETION INLOCUS 2Q24.3. A CASE REPORTE. Szczepanik, D. Hoffman-Zacharska, A. Jeziorek Anetta,I. Terczynska, and J. BalInstitute of Mother and Child, Warsaw, Poland

Purpose: To report on 5.5 year-old-girl with Dravet syndrome and withsevere pattern-sensitivity

Method: Clinical, EEG and genetic data were analyzed

Result: The patient was a healthy female born at term. Her maternalgrandmother suffered from epilepsy considered as postraumatic. At theage of 4 months she had her first febrile seizure as cluster of myocloniaslasting 40 minutes. Since 11 months of age she developed both febrileand afebrile seizures of different types encompassing GTCSs, myoclo-nias, absences, focal seizures, and a few status epilepticus. Parentsnoticed that most seizures occurred while watching almost any strip pat-terns. EEG showed brief generalized spike-waves, polyspikes-waves par-oxysms and focal spikes as well, with IV grade photosensivity andphotoconvulsive response. MRI/ MRS of brain were normal. Dravet syn-drome was suspected and molecular analysis of the SCN1A gene per-formed. Genetic testing revealed on point mutations in the SCN1Acoding sequence, but deletion of the size 1.5Mb on the one chromosome2, in locus 2q24.3, encompassing the whole SCN1A gene and six addi-tional, of which SCN9A may act as phenotype modifier. The patient wastreated with many AEDs without effect. Stiripentol was added to VPAand clobazam at the age of 4 years, and she has had two febrile GTCSssince then. Her cognitive development has slown down, however it is stillwithin normal range, but she exibits mild cerebellum ataxia.

Conclusion: Such extensive mutation of SCN1A gene might be consid-ered as important cause of such severe photosensitivity in our patient.

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p813NEONATAL CEREBRAL SINOVENOUS THROMBOSIS(CSVT) WITH THALAMIC HAEMORRHAGE ISSTRONGLY RELATED TO ELECTRICAL STATUS EPI-LEPTICUS IN SLEEP (ESES)F. E. Jansen*, K. Kersbergen�, K. P. J. Braun�, F. S. S. Leijten§,R. J. Nievelstein*, F. Groenendaal�, M. Benders�, and L. S. DeVries–

*University Medical Center Utrecht, Utrecht, The Netherlands;�UMC, Utrecht, The Netherlands; �Rudolf Magnus Institute ofNeuroscience, University Medical Center Utrecht, Utrecht, TheNetherlands; §UMC Utrecht, Utrecht, The Netherlands; and–Wilhelmina Children's Hospital, Utrecht, The Netherlands

Purpose: To assess the prevalence of electrical status epilepticus insleep (ESES) and postneonatal epilepsy after neonatal cerebral sinove-nous thrombosis (CSVT) associated with a thalamic haemorrhage.

Method: We included thirteen children (age 2–8 years) diagnosed,between 2003 and 2008, with neonatal CSVT, and an associated thalamichaemorrhage (assessed on MRI), in the University Medical Center Utr-echt, the Netherlands. Neurodevelopment and seizures history were rou-tinely followed up in the outpatient clinic. Sleep EEG recordings wereperformed to assess the prevalence of ESES; defined as a spike waveindex (SWI) exceeding 60%, and confirm the diagnosis of epilepsy.

Result: Four children were diagnosed with ESES syndrome. Three pre-sented with seizures, and one showed inattentiveness, suspected ofabsences. Sleep induced epileptiform activity < 60% (ESES spectrum)was seen in two children, of whom one had seizures and the other a learn-ing disability. Three children were diagnosed with focal epilepsy withpartial seizures, in the absence of ESES. Of the four with a normal EEG,one had a global developmental delay. Two of the 13 children had devel-oped a mild hemiplegia.

Conclusion: Neonates with a thalamic haemorrhage, associated with astraight sinus thrombosis, are at high risk of developing ESES (spectrum)syndrome (46%) and focal epilepsy (31%). Electrographical findingswere already present at a young age, in some cases even before cognitivedeficits were recognised. Early diagnosis and subsequent treatment mayprevent cognitive deterioration. Routine annual sleep EEG recordings arerecommended in children with neonatal thalamic injury.

p814EARLY EPILEPTIC ENCEPHALOPATHIES ASSOCI-ATED WITH STXBP1 MUTATIONS: COULD WE BET-TER DEFINE THE PHENOTYPE?G. Barcia*, N. Chemaly*, S. Gobin*, M. Milh�, P. Van Bogaert�,C. Barnerias*, A. Kaminska*, O. Dulac*, V. Cormier*,N. Boddaert*, and R. Nabbout**Hopital Necker Enfants Malades, Paris, France; �Hopital LaTimone, Marseille, France; and �Hopital Erasme, Bruxelles,Belgium

Purpose: STXBP1 (MUNC18.1), encoding syntaxin binding protein 1,is a new gene causing early epileptic encephalopathy. Heterozygousmutation in STXBP1 have first been reported in Ohtahara syndrome(EOEE) (Saitso et al., 2008), then in patients affected by infantile spasms(IS) (Otsuka et al., 2010) and, more recently, in patients with non syndro-mic mental retardation without epilepsy (Hamdan et al., 2011). To betterdefine the clinical phenotype and to determine the occurrence of specificneuroradiological abnormalities in patients with STXBP1 mutations, weanalyzed clinical and neuroradiological findings in a series of patientshaving STXBP1 mutations

Method: We included patients with STXBP1 abnormalities followed atour institutions and who underwent a high resolution brain MRI.

Result: We identified 7 unrelated children (6 females, 1 male) withSTXBP1 mutations. Age at seizure ranged from 1 day to 3 months. Allchildren presented with IS and 5 had a ‘‘suppression-burst’’ pattern onEEG. Although all patients were seizure free on AEDs by the age of 2years, they showed global and severe developmental delay. Neuroimaginganalysis showed a peculiar aspect of slight and dysmorphic corpus callo-sum (6/7 patients) associated with cortical frontal atrophy (4/7 patients).

Conclusion: STXBP1 mutations are detected only in a minority ofpatients with early epileptic encephalopathy. We suggest with thin anddysmorphic corpus callosum and frontal cortical hypoplasia on brainMRI, especially if seizures are controlled in the first years, could repre-sent the best candidates to genetic analysis of STXBP1.

p815A ROLE FOR THE CXCR3/CXCL10 AXIS IN RASMUS-SEN ENCEPHALITIS. A NEW TARGET FOR IMMUNO-THERAPHY?M. P�rez-Jim�nez*, I. De Prada*, I. Mirones�, A. G�mez*,A. Luque*, R. Mart�n*, F. Villarejo*, J. Garc�a-Castro�,L. Madero*, and M. Ramirez Orellana**Hospital Infantil Universitario NiÇo Jesffls, Madrid, Spain; and�Instituto De Salud Carlos Iii, Madrid, Spain

Purpose: Previous studies suggest that the effector lymphocytes respon-sible for the brain destruction in Rasmussen Encephalitis (RE) migratefrom the periphery to the cerebral parenchyma, where they cause thedamage. The purpose of our study was to gain information about themolecular basis of the recruitment of T lymphocytes from the peripheryto the areas of brain destruction in patients with RE.

Method: We have studied the implication of CXCL10-CXCR3 in RE, achemotactic axis involved in the pathogenesis of several cases of immuneencephalitis, by analysisng pathological specimens of 6 children with REand by functional in vitro assays.

Result: We found that cytotoxic T lymphocytes infiltrating the damagedareas of primary biopsies expressed CXCR3, while neurons and astro-cytes in the same areas expressed CXCL10. In in vitro assays, we foundthat astrocytes upregulated the expression of CXCL10 mRNA, and therelease of CXCL10 to the supernatants, upon stimulation with Polyino-sinic-polycytidylic acid (Poly (I:C), a synthetic dsRNA which mimicsinfections with either RNA or DNA viruses. Activated T lymphocytesresponded to the production of CXCL10 by Poly (I:C)-stimulated astro-cytes by increasing their migration in a transwell assay. Finally, the che-motaxis induced by the stimulated astrocytes was completely abrogatedin the presence of small molecules antagonists of CXCR3.

Conclusion: Our results show that the CXCR3-CXCL10 axis has a rolein recruiting pathogenic T lymphocytes into the brains of RE patients,and that this finding may be targeted pharmacologically.

p816ABSENCE OF THALAMIC METABOLIC CHANGE INEPILEPSIES WITH CONTINUOUS SPIKE-WAVES DUR-ING SLEEPN. Ligot*, F. Archambaud�, N. Trotta*, S. Goldman*, P. VanBogaert*, C. Chiron�, and X. De Tiege**Universit� Libre de Bruxelles, Brussels, Belgium; and �Inserm,Paris, France

Purpose: Some evidence suggests that the thalamus might play a keyrole in the pathophysiology of epileptic encephalopathies with continu-ous spike-waves during sleep (CSWS). Previous studies investigatingregional metabolic changes associated with CSWS activity compared the

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brain metabolism of children with CSWS with that of healthy adults, pre-cluding any assessment in brain areas showing physiologic age-relatedmetabolic changes such as the thalamus.

Method: Positron emission tomography using [18F]-fluorodeoxyglu-cose (FDG-PET) was performed in 15 children at the acute phase ofCSWS (3 girls, age: 5 to 11 years). Voxel-based analyses identified sig-nificant metabolic changes in patients compared to a paediatric controlgroup (12 girls and 6 boys, age: 6 to 11.5 years, focal cryptogenic epi-lepsy with normal FDG-PET) using SPM8. Age-related metabolicchanges were identified by comparison of FDG-PET data obtained inpatients, paediatric controls and healthy adults (15 women, age: 18 to 51years).

Result: Hypermetabolism in centro-temporal regions bilaterally andhypometabolism in the prefrontal cortex, the precuneus, the posteriorcingulate cortex and parahippocampal gyri characterized the acutephase of CSWS (p inf. 0.05, FWE). Although highly significant tha-lamic hypometabolism was found in both paediatric populations com-pared to adults, no change in this sub-cortical structure was found inpatients compared to paediatric controls, even at very low threshold (pinf. 0.05 uncorrected).

Conclusion: This study suggests that CSWS is not associated with sus-tained changes in thalamic metabolism. These data further demonstratethat CSWS activity is associated with hypermetabolism at the site of theepileptic focus and hypometabolism in remote cortical areas.


p817PERSISTENT CONNECTIVITY DURING AWAKE ANDSLEEP OF BRAIN LOCATIONS GENERATING CON-TINUOUS SPIKE AND WAVES DURING SLOW SLEEP(CSWS)P. G. Larsson*, M. L. Stavrinou�, D. Kugiumtzis�, and J.F. Storm�

*Oslo University Hospital, Nydalen, Norway; �University ofOslo, Oslo, Norway; and �Aristotle University of Thessaloniki,Thessaloniki, Greece

Purpose: Continuous spike and waves during slow sleep (CSWS) is acondition encountered in children with epileptiform activity seen in theirsleep Electroencephalograms. Various neuropsychological impairmentsare often seen in children with CSWS, like language, speech and learningdisabilities or general cognitive deterioration. The mechanisms of thisepileptiform-related cognitive dysfunction are poorly understood. Theaim of this study was to evaluate brain connectivity patterns duringawake and sleep in children with CSWS without any other epilepticpathology.

Method: 24-hour electroencephalographic recordings of 10 childrenadmitted to the National hospital in Oslo were analyzed using differentconnectivity methods: correlation, partial correlation and Directed Trans-fer Function.

Result: Our results showed that the areas that generate this spike activitycontinue to participate in brain networks also during wakefulness and notonly during sleep when this activity is maximal. The strength of connec-tions and the appearance rate in brain networks did differ significantlybetween sleep and wakefulness.

Conclusion: This persistent participation of spiking locations also dur-ing wakefulness is possibly causing functional changes to the normalbrain connectivity patterns. This finding may help explain why cognitivedeterioration occurs in children with CSWS.

p818A SLC2A1 MUTATION IN A BOY WITH CHILDHOODABSENCE EPILEPSY, ALTERNATING HEMIPLEGIAAND ATAXIAH. Muhle, F. Mçller, U. Stephani, and I. HelbigUniversity Medical Center Schleswig-Holstein, Kiel, Germany

Purpose: Mutations in SLC2A1 (solute carrier family 2, member 1)cause a broad range of neurological disorders. Main features are move-ment disorders and childhood epilepsies, especially early onset absenceepilepsy. The role of SLC2A1 in childhood and juvenile absence epilep-sies, however, seems to be less important. Here we describe a patient withthe rare combination of childhood absence epilepsy (CAE), alternatinghemiplegia and mild ataxia.

Method: The clinical course of a patient with CAE and additional neu-rological features is described. Analysis of SLC2A1 was performed usingSanger sequencing.

Result: The boy was affected by left-sided hemiplegia and aphasia atthe age of 6 ½ years lasting for two hours. MRI and EEG were unremark-able. 9 months later, a second period of right-sided hemiplegia with apha-sia was observed. EEG showed 3 Hz spike-wave paroxysms lasting for 4seconds, accompanied by previously unnoticed loss of consciousnessconsistent with CAE. Mild ataxia was observed on neurological examina-tion. The boy became seizure-free with valproate monotherapy. A patho-genic mutation in SLC2A1 was identified (c.274 C>T, p.Arg92Trp).

Conclusion: The occurrence of SLC2A1 mutations in patients withCAE and alternating hemiplegia is unusual and our patient furtherexpands the spectrum of GLUT1 deficiencies. GLUT1 mutations shouldbe considered as an underlying cause when CAE coexists with additionalneurologic features.

p819EYELID MYOCLONIA WITH ABSENCES (JEAVONSSYNDROME): A LIFE LONG DISORDER WITH MILDCOGNITIVE IMPAIRMENT?H. T. Ong*, and K. J. Lim�

*National University Hospital, National University HealthSystem, Singapore, Singapore; and �Yong Loo Lin School ofMedicine, National University of Singapore, Singapore,Singapore

Purpose: Following clear clinical description of eyelid myoclonia withabsence (EMA) by Jeavons in 1977, several authors have reported similarpatients. However, EMA has not yet been recognized as a distinct epilep-tic syndrome by the ILAE. The treatment response, possibility of longterm remission and the association if any of cognitive impairment, is stillpoorly understood

Method: We retrospectively reviewed children with EMA in our EEGdatabase. These are neurologically normal children who had clinical pre-sentation of eyelid myoclonia with absences. The diagnosis was con-firmed by the presence of 3–6 Hz generalized spike-waves or polyspike-waves, with ictal manifestation of eyelid myoclonia and absence, provenon simultaneous video-EEG

Result: Two girls fulfilled the diagnosis of EMA. The onset of seizureswas at 2.5 years and 7 years respectively. Seizure control was achievedwith valproic acid (VPA) monotherapy. The first patient remained sei-zure-free for 3 years with seizure recurrence 9 months after weaning offVPA. The second patient had seizure recurrence when she was brieflynon-complaint after remaining seizure-free for 2 years whilst on VPA.Although both girls had normal developmental milestones in early child-hood, their academic performances were below average when comparedto their peers in school. The clinical features and EEG findings in our

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patients with EMA are similar to those reported worldwide. Although sei-zure-free remission is easily achieved with VPA and sustained for 2 to 3years, seizure recurrence is likely when VPA is weaned off or stopped.Our patients also had below average academic performance in school.

p820RESULTS OF THE STUDY OF HORMONES IN BLOODOF GIRLS WITH EPILEPSYV. I. Guzeva, and V. V. GuzevaSaint-Petersburg Pediatric Medical Academy, Saint-Petersburg,Russian Federation

Purpose: Investigation of thyroid, parathyroid and adrenal hormones inblood of girls with epilepsy

Method: Investigation of thyroid hormones –thyrotropin, antibodes tothyroglobulin, triiodthyronine, thyroxine, parathyroid hormone and corti-sol in blood of 50 girls with epilepsy and 47 of control group in the agegroups 8–9, 10–11, 12–13, 14–15 and 16–17 years was conducted.

Result: Investigation of changes in hormone levels in blood of girls withepilepsy and control group according to age revealed that girls with epi-lepsy 8–9, 10–11, 12–13, 14–15 and 16–17 years in most cases (86.67%)had levels of these hormones in blood higher than the control group ofgirls the same age. In 30% of cases the content of hormones in blood ofgirls with epilepsy was significantly higher (p ‡ 0.90), than in controlgroup. In blood of girls with epilepsy 16–17 years levels of all hormonesexceeded those in blood of control group, and for triiodthyronine, cortisoland parathyroid hormone the difference was significant (p ‡ 0.90), whilein blood of girls 14–15 years significant difference was found for triiod-thyronine and cortisol, in blood of girls 12–13 years- for thyrotropin, 10–11 years- for cortisol, 8–9 years- for thyrotropin and cortisol. Significantreduction in level of hormones in blood of girls with epilepsy comparedwith control group in subgroups 8–9, 10–11, 12–13, 14–15 and 16–17years were not found.

Conclusion: So, the content of cortisol in blood of girls with epilepsywas significantly higher in all age groups except for 12–13 years.

p821LONG TERM OUTCOMES OF EPILEPSY SURGERY INSCHOOL-AGE CHILDREN WITH PARTIAL EPILEPSYS. Liang, Z. Zhang, and X. HuFirst Affiliated Hospital of PLA General Hospital, Beijing,China

Purpose: To compare surgical outcomes of school age children (SAC)with intractable partial epilepsy from China and those from developedcountries, and introduce surgical candidate selection.

Method: We retrospectively selected 206 SAC aged 6–14 years withepilepsy surgery in our center from Sep., 2001 to Jan., 2007. We analyzedpatient's general clinical features, examinations, treatments, and surgicaloutcomes, including seizure control at 1 year follow-up (1FU), 3 years(3FU) and 5 yrs (5FU) after operation, and changes of intelligence quo-tient (IQ), memory quotient (MQ) and QOL from preoperative to 2FU.Also, the effects of surgical outcomes were analyzed.

Result: Postoperative seizure freedom was rendered in 173 cases (84.0%)at 1FU, 149 (72.3%) at 2FU, and 139(67.5%) at 5FU, and patients withfocal MRI abnormalities and short history of seizure were likely to obtainpostoperative seizure free. patients with preoperative low-IQ and childrenwith seizure free rendered full MQ, IQ and overall QOL improvement at2FU, and the significant differences were found in the mean changes offull IQ, full MQ, overall QOL between patients with preoperative low-IQand corpus callosotomy and those with normal IQ, and between childrenwith seizure free and those with continual seizure attack.

Conclusion: Epilepsy surgery is promising for seizure control andimprovements of QOL, MQ and IQ in carefully selected SAC with intrac-table partial epilepsy, the surgical outcomes in China were not less thanthe data from developed countries. Early surgery should be taken intoconsideration in SAC with focal lesions. School-age children with low-IQ and generalized epileptiform discharge could not be excluded from re-sective epilepsy surgery.

p822DETECTION OF EPILEPTIC SEIZURE IN CHILDRENUSING NON-LINEAR ANALYSIS IS HRVV. Kharytonov*, I. Chaikovsky�, V. Bukhman�, Y. Frolov�, andV. Mishiev**Kyiv's Municipal Psycho-Neurological Hospital #1, Kiev,Ukraine; �International Research and Training Center of NAS ofUkraine, Kiev, Ukraine; and �Biosignal Consulting, New York,IL, USA

Purpose: It is known fact that during epilepsy seizure HR significantlyincreases. It also affects HRV. We hypothesized that changes of non-lin-ear parameter SampEn may indicate ictal period of epilepsy seizure moreprecisely then HR changes.

Method: Patients group: 24 patients (12 boys, 12 girls), age 2m –25years (mean 7.1 y) All the patients underwent vEEGmonitoring withpolisomnography for 12 hours with detection of paroxysmal events ofvarious etiology. Focal seizures: 11 patients Generalised seizures: 6patients Control group of 7 patients with nonepileptic paroxysms In addi-tion to HR, Sample Entropy as a measurement of complexity of time ser-ies of RR intervals, {RR1, RR2, RR3, …RRi…RRn was calculated.Genetic algorithm was used to define the threshold value of these twoparameters.

Result: In group with focal seaizures, sensitivity of seizure detection bySampEn was 100%, by HR – 78%, specificity – 96% and 70% respec-tively. In group with generalized seizure accuracy of seizures detectionby SampEn was significantly lower and comparable with accuracy of sei-zure detection using HR.

Conclusion: Non-linear analysis of HRV is more accurate then HRchanges in epileptic seizure detection in patients with focal seizures. Fur-ther research needed to confirm these findings

p823THE SPECTRUM OF BENIGN INFANTILE SEIZURESINCLUDING BENIGN INFANTILE SEIZURES WITHMILD GASTROENTERITIS, BENIGN INFANTILEFOCAL EPILEPSY WITH MIDLINE SPIKES ANDWAVES DURING SLEEP AND OTHERSI. Y. SaadeldinTawam Hospital, Al Ain, United Arab Emirates

Purpose: To highlight the characteristic features of Benign InfantileSeizures and demonstrate the benign nature of the syndrome. The syn-drome includes many new entities. The aim of this review is to describethese entities, discuss their nosological aspects, compare our results withthe international studies and demonstrate by videos the characteristicelectroclinical features.

Method: Two studies were performed: 1. A case series of 275 patientswith epileptic seizures who fulfilled the criteria of BIS were followedover a period of 3 years and 7 months which included patients with parox-ysmal dyskinesia2. Twenty-five patients who fulfilled the diagnostic cri-teria for benign infantile seizures with mild gastroenteritis were assessedand followed between January 2004 and January 2009.

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Result: In 2009, Saadeldin et al. documented for the first time the pres-ence of benign infantile seizures (Fukuyama-Watanabe–Vigevano syn-drome) in Saudi Arabian and Arab populations. The authors highlightedthe characteristic features of BIS and demonstrated the benign nature ofthe syndrome. One year later, Saadeldin analyzed the electroclinical fea-tures of patients with benign infantile seizures with mild gastroenteritis(BIS with MG) and demonstrated the benign nature of this entity.

Conclusion: Increasing the awareness of clinicians regarding the exis-tence of these syndromes and their benign nature in children will limitunnecessary investigations.

p824POTENTIALLY SEIZURE PROVOKING VIDEOSEQUENCES IN SPANISH TV: THE SMOKING GUNJ. Parra*, B. Anciones*, M. Hodgetts�, D. Jackson�, andG. F. Harding�

*Hospital de La Zarzuela y Ntra SeÇora del Rosario, Madrid,Spain; �Cambridge Research Systems Ltd, Rochester, Kent, UK;and �ElectroDiagnostic Centre, Greenfields, Worcester, UK

Purpose: To analyse systematically the content of potentially seizureprovoking video sequences from different Spanish television broadcast-ers checking for compliance with current guidelines in other countries.One in 4000 subjects is at risk of having a seizure when confronted withcertain visual stimuli, often without being aware of their condition. Tele-vision is the most common cause of photosensitive seizures in the wes-tern world, but only the UK and Japan have adopted guidelines to preventthe broadcasting of video sequences that could potentially trigger sei-zures in susceptible people.

Method: Television programs of all 5 national broadcasters availablevia Digital Terrestrial Television were recorded between 8 AM and 12PM on 5 consecutive days, from January 1st 2012 through January 6th2012. In addition, a channel with programming dedicated to children anda musical channel were also recorded. The video content was analysedusing a HardingFPA Flash and Pattern Analyser (Cambridge Researchsystems) for compliance with the UK Ofcom guidelines.

Result: We analysed 105 hours of television programs. We found 738incidents that violated the guidelines (mean 105.43, CI95% 58.74–151.12), mostly luminance flashing (714 incidents, mean 102, CI95%55.83–148.17). Thirteen incidents involved spatial patterns and 11 redflashing. Forty-seven additional incidents considered dangerous weredetected which, although technically meeting guidelines, continued foran extended period of time and were considered dangerous.

Conclusion: Spanish broadcasters seem to be unaware of the risk ofphotosensitive epilepsy. National Guidelines should be adopted to lowerthe risk of Spanish TV content triggering epileptic seizures in susceptibleviewers.

p825THROMBIN FACILITATES SEIZURES THROUGHACTIVATION OF NEURONAL PERSISTENT SODIUMCURRENT: A NEW MECHANISM OF SEIZURE DEVEL-OPED DURING INTRACEREBRAL HEMORRHAGEO. Isaeva*, A. Hernan�, D. Isaev*, and G. L. Holmes�

*Bogomoletz Institute of Physiology, Kiev, Ukraine; and�Dartmouth Medical School, Lebanon, NH, USA

Purpose: An epileptic seizure is frequently the presenting sign of intra-cerebral hemorrhage (ICH) caused by stroke, head trauma, hypertensionand a wide spectrum of disorders. However the cellular mechanismsresponsible for occurrence of seizures during ICH have not been estab-

lished. During intracerebral bleeding blood constituents enter the neuro-nal tissue and produce both an acute and delayed effect on brainfunctioning. Among the blood components only thrombin has beenshown to evoke seizures immediately after entering brain tissue. In thepresent study we tested the hypothesis that thrombin increase neuronalexcitability in the immature brain through alteration of voltage-gatedsodium channels.

Method: The thrombin effect on neuronal excitability and voltage-gatedsodium channels was assessed using extracellular and intracellularrecording techniques in the hippocampal slice preparation of immaturerats.

Result: We show that thrombin increased neuronal excitability in theimmature hippocampus in an NMDA-independent manner. Applicationof thrombin did not alter transient voltage-gated sodium channels andaction potential threshold. However thrombin significantly depolarizedthe membrane potential and produced a hyperpolarizing shift of TTXsensitive persistent voltage-gated sodium channel activation. This effectof thrombin was attenuated by application of protease-activated receptor-1 and protein kinase C antagonists.

Conclusion: Our data indicates that thrombin amplifies of the persistentvoltage-gated sodium current affecting resting membrane potential andseizure threshold at the network level. Our results provide a novel expla-nation as to how ICH in newborns results in seizures, which may provideavenues for therapeutic intervention in the prevention of post-ICH sei-zures.


p826PARTIAL POSTERIOR EPILEPSIES WITH PERSIS-TENT FIXATION OFF SENSITIVITY IN ADULT LIFE:ELECTRO-CLINICAL EVALUATION, NEUROIMAG-ING FEATURES AND EPILEPTIC SYNDROME DEFINI-TIONJ. Fattouch, A. Morano, A. T. Giallonardo, L. Lapenta,S. Casciato, M. Fanella, M. Manfredi, and C. Di BonaventuraPoliclinico Umberto I, Rome, Italy

Purpose: The term Fixation of Sensitivity (FOS) was proposed by Pana-yiotopoulos to describe epilepsy/EEG change evocated by the suppres-sion of central vision and fixation. The EEG pattern usually consists ofspike/polyspike and waves localized in occipital regions. FOS occursmainly in children with idiopathic occipital partial epilepsies and rarelyin adults. In this retrospective study we evaluated clinical data/EEG/MRIfindings of 15 epileptic patients with FOS persisting in adult life to betterdefine the spectrum of syndromes.

Method: We selected 15 consecutive patients (12 females/3 males; agerange: 19–59 years). The main inclusion criterion was the diagnosis ofepilepsy with FOS persisting in adult life. We retrospectively analyzedclinical/EEG/ neuroimaging data.

Result: We observed a female prevalence (F/M=12/3). 8 patients pre-sented both simple and complex partial seizures whereas 7 had only com-plex seizures. Partial seizures evolved into generalized in 9 cases. TheFOS pattern consisted of spike-and-wave and slow-wave abnormalitieswith a posterior localization (bilateral in 9/monolateral in 6). Werecorded seizures in 10/15 patients. All showed a posterior onset (bilat-eral in 2/left in 2/right in 6). FOS was prevalent in symptomatic epilepsy(cortical malformations in 7; coeliac disease in 3; vascular malformationin 1; calcifications in 1). One patient presented a probably symptomaticepilepsy and only 2 an idiopathic syndrome (Gastaut syndrome).

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Conclusion: FOS can be observed in adult life in idiopathic epilepsy,representing the ‘‘prolongation’’ of the same phenomenon arisen duringchildhood. Nevertheless, it often represents the EEG expression of symp-tomatic epilepsies (cortical malformations/coeliac disease).

p827DISTRIBUTION OF PROGRESSIVE MYOCLONUS EPI-LEPSIES IN ITALY; POSITIVELY DIAGNOSED ANDUNCLASSIFIED PATIENTSL. Canafoglia*, S. Franceschetti*, R. Michelucci�,A. Magaudda�, G. Rubboli�, P. Tinuper§, P. Striano–,S. Striano**, A. Gambardella��, A. La Neve��, T. Francavilla��,E. Ferlazzo§§, D. Italiano§§, G. Gobbi––, F. Villani*,N. Nardocci*, T. Granata***, P. Veggiotti��, D. Pareyson*,G. Coppola��, G. Uziel***, V. Belcastro§§§, F. Bisulli§,R. Spreafico–––, R. Guerrini****, M. Viri��, C. Zucca��,G. Capovilla§§§§, A. R. Giovagnoli*, M. P. Canevini––––,S. Binelli*, M. Casazza*, A. T. Cantisani*****, A. Filla**,M. Pezzella**, M. Santucci��, A. Parmeggiani��,A. Posar��, G. De Maria��, C. Marini§§§§§, A. Bianchi–––––,F. Ragona***, E. Freri***, C. Mariotti*, and P. Costa******

*IRCCS Foundation Besta Neurological Institute, Milan, Italy;�Bellaria Hospital, Bologna, Italy; �University of Messina,Messina, Italy; §Bologna, Italy; – ’’G. Gaslini’’ Institute,University of Genova, Genova, Italy; **Federico II’’ Universityof Napoli, Napoli, Italy; ��University Polyclinic, Catanzaro,Italy; ��Bari Polyclinic, Bari, Italy; §§IRCCS Neurolesi, Messina,Italy; –– ’’Maggiore’’ Hospital of Bologna, Bologna, Italy;***IRCCS Foundation Neurological Institute C. Besta of Milan,Milan, Italy; ��IRCCS Monzino, Pavia, Italy; ��University ofSalerno, Salerno, Italy; §§§S. Anna Hospital, Como, Italy;–––I.R.C.C.S. Foundation Neurological Institute, Milan, Italy;****University of Florence, Meyer Hospital, Florence, Italy;��Fatebenefratelli hospital, Milan, Italy; ��IRCSS La NostraFamiglia, Bosisio Parini, Italy; §§§§Hospital of Mantova,Mantova, Italy; ––––S. Paolo Hospital, University of Milan,Milan, Italy; *****Perugia, Italy; ��University of Bologna,Bologna, Italy; ��Brescia, Italy; §§§§§Florence, Italy;–––––Arezzo, Italy; and ******Trieste, Italy

Purpose: Progressive myoclonus epilepsies (PMEs) result from severalgenetic disorders. Few information are available about the prevalence ofdifferent PMEs. In spite of the progress in bio-molecular fields, the caus-ative disorder remains undiagnosed in a significant fraction of thepatients presenting with a PME phenotype. The aim of this study was col-lecting information about the frequency and geographical distribution ofPMEs in Italy.

Method: The Genetic Commission of the Italian League against epi-lepsy set up a data-base to include information dealing with PME patientsreferred by Italian Epilepsy Centres, including the following information:geographical origin of the parents, consanguinity, familiarity, age at thedisease and myoclonus onset, general characteristics of the seizures andmyoclonus and associated neurological defects, positive diagnosis, whenreached. Negative results obtained in the different examinations per-formed during the diagnostic work-up had to be explicitly reported forthe patients who didn't reach a positive diagnosis of the neurological dis-order underlying the PME phenotype.

Result: We collected 179 patients, including 74 with Unverricht-Lund-borg disease, 33 with Lafora body disease, 25 with PME forms resultingfrom more rare genetic causes (neuronal ceroid-lipofuscinosis, actionmyoclonus renal syndrome, mitochondrial encephalopathies, other meta-

bolic disorders, celiac disease). Forty-seven patients were not classified,in spite of several investigations. We performed a tentative sub classifica-tion of these patients, based on details of phenotypic presentation (onsetage, presence of relevant cognitive decline, seizure frequency and associ-ated neurological signs).

Conclusion: This study is expected to support further genetic studiessuitable to detect new diseases giving rise to the PME phenotype.

p828COMORBIDITIES IN ROLANDIC EPILEPSYY. A. Hernandez Vega*, S. Tang�, A. Smith*, T. Clarke�, andD. K. Pal§

*Clinical Neuroscience PO43, London, UK; �King's CollegeHospital, London, UK�Columbia University, New York, NY,USA; and §King's College London, London, UK

Purpose: Rolandic Epilepsy (RE) has been associated with several neu-rocognitive (speech sound disorder, reading disability, ADHD) and neu-rological (migraine) comorbidities. There is evidence that thesecomorbidities are not only familial but genetic in origin. Our objective isto estimate the distribution of comorbidities in RE patients and siblings.

Method: We recruited RE 105 patients and their 130 siblings for agenetic study from 2004 to 2012 in the USA and UK. We systematicallyand prospectively collected data on demographic, seizure and treatmentvariables, speech sound disorder, reading disability, ADHD, migraineand school failure. We calculated Mantel-Haenszel odds ratios of associ-ation using STATA, adjusting for demographic and clinical variables.

Result: 40% of probands had reading disability; 40% school failure;30% speech sound disorder; 18% ADHD symptoms; and 13% migraine.Among siblings, 20% had reading disability; 22% school failure; 18%speech disorder; and 11% migraine. 53% of probands had at least oneneurocognitive comorbidity and 32% of siblings had at least one lan-guage-related comorbidity. In multivariate analysis, reading disability isthe only independently associated risk factor for school failure (OddsRatio=104) after adjusting for speech sound disorder, ADHD, age atonset, seizure frequency, and treatment.

Conclusion: Over half of RE patients and one-third of their siblings areat risk of neurocognitive comorbidities. School failure occurs in a veryhigh proportion of patients and siblings and is predicted by reading dis-ability. RE patients should be neuropsychologically evaluated early inthe course of disease to mitigate educational complications. Familiesshould be advised about the risk of neurocognitive impairments in sib-lings

p829ELECTROENCEPHALOGRAPHIC FOCAL DIS-CHARGES WITH OR WITHOUT CLINICAL MANIFES-TATIONS IN CHILDREN WITH CHILDHOODABSENCE EPILEPSYZ. Sabol, M. Kovac Sizgoric, and F. SabolSabol Clinic for Sick Children, Zagreb, Croatia

Purpose: The aim of this study was to establish the frequency of focalelectroencephalographic (EEG) discharges with or without clinical mani-festations in children with childhood absence epilepsy (CAE).

Method: Patients and methods: During 13-years period (1998–2011) wehave been treated and followed-up 81 patients (39 girls and 42 boy), atthe age from 1.8 to 13.5 years (median age 6.9 years) with typicalabsences. Average duration of clinical follow-up was six years.

Result: Results: In 13/81 (16%) children with CAE focal EEG dis-charges were revealed changes identical to those in benign partial epilep-

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sies (BPE). Six from 11 patients manifested also partial seizures suitablefor Panayiotopoulos syndrome (PS) (4), benign rolandic epilepsy (1) andbenign partial epilepsy with occipital paroxysms - Gastaut type (1patient). The age of children at the time of the first partial seizure was 1.7- 11 years. In all patients the absence seizure control was achieved insidesix weeks - 11 months. Focal EEG discharges were disappeared in 10/13patients, in three are still present, but without relapse of partial seizures.

Conclusion: Evidence of focal EEG discharges, with or without evidentpartial seizures in patients with CAE is rare, but possible. Although rela-tionship between partial and generalized seizures in the same patient canbe coincidental, the posibility of its genetic linkage cannot be excluded.Further clinical investigations about clinical and EEG features, the resultsof treatment and establishment of long-term prognosis in these patientscould lead us to the definition of special form of CAE.

p830EPILEPSY AND PCDH19 MUTATION CLINICAL ANDELECTROPHYSIOLOGICAL FEATURES IN 13PATIENTSN. Chemaly*, A. Kaminska*, J. M. Pinard�, A. Gauthier�,C. Chiron§, I. An–, I. Desguerre§, N. Bahi Buisson§, O. Dulac§,and R. Nabbout**Hopital Necker Enfants Malades, Paris, France; �HpitalRaymond Poincar�, Garches, France; �CHU Nantes - HpitalM�re enfant, Nantes, France; §Hpital Necker Enfants Malades,Paris, France; and –Hpital Piti� SalpÞtri�re, Paris, France

Purpose: Mutations in PCDH19 gene were described in Epilepsy inFemale with Mental Retardation and in patients presenting an epilepticencephalopathy similar to Dravet syndrome.

Method: In order to precise the clinical and electrophysiological pheno-type associated with PCDH 19 mutation, we included 13 patients fol-lowed in our institution with a mutation in this gene. We retrospectivelyreviewed clinical history, seizure and EEG characteristics, cognitive andbehavioral assessment.

Result: Seizures were mainly focal at onset. Fever susceptibility was notsystematic at onset (4/13 patients) but was found in all patients duringfollow-up. Seizures occurred in clusters of focal or generalized seizures,mainly during febrile episodes. Early EEGs recordings before the age of12 months showed diffuse rhythmic slow wave with fast activity. Duringseizures clusters, we recorded seizures with temporal or frontal onset andinterictal focal spikes and slow waves in the same regions. During fol-low-up, interictal EEG showed generalized slowing of the back groundactivity, theta activities in the central regions. The frequency of clustersdecreases during the second decade, being less than once a year in 5patients with one patient seizure free without AEDs. Cognitive impair-ment is constant after the age of 3. Autistic features were confirmed in 3patients. Psychiatric features consist of aggressive and frontal behavior.

Conclusion: This phenotype seems different from Dravet syndromephenotype regarding semiology of seizure, onset of fever susceptibility,cognitive impairment and psychiatric symptoms. The phenotypic spec-trum is homogeneous in this cohort and helps to better delineate thePCDH19 mutations phenotype.

p831FEAR TOWARDS THE ANTIEPILEPTIC THERAPYWITHDRAWALM. F. Knezevic-PogancevInstitute for Child and Youth Health Care of Vojvodina, NoviSad, Serbia

Purpose: The decision of antiepileptic drugs withdrawal is mostly basedon a balanced view of the overall risk of seizure relapse and factors most

likely to affect that risk. The aims of study was to determine patient andfamily attitudes towards the fear of antiepileptic drug withdrawal, afterthree years of seizure controle.

Method: This research was carried out in the Institute for Child andYouth Health care of Vojvodina. During the study, which lasted from2003 to 2008, a face-to-face interview about fear of antiepileptic therapywithdrawal was done, during adolescent patient examination. Study pop-ulation included 150 adolescent patients, and 265 their parents.

Result: Accepted risk in general is higher in our adolescent patientsgroup than in parents group (p<0.05). This risk over 50% seem excessiveto all parents, but not to all adolescent patients.

Conclusion: Its important to admire adolescent patients and their par-ents fear towards the risk of antiepileptic drug withdrawal.

p832FOCAL EPILEPTIFORM DISCHARGES IN PEDIATRICPATIENTS WITH IDIOPATHIC GENERALIZED EPI-LEPTIC SYNDROMESN. ErmolenkoVoronezh State Medical Academy, Voronezh, RussianFederation

Purpose: The occurrence of focal and clinical EEG abnormalities in cer-tain idiopathic generalized epilepsy (IGE) syndromes is common andmay require extensive study to make a differential diagnosis. The aim ofthis study was to identify the prevalence of various focal electroencepha-lographic and/or clinical features in patients with different forms of IGE,required video-EEG monitoring.

Method: We retrospectively studied 71 patients younger than 18 yearsof age (31 males and 42 females) with IGE who underwent video EEGmonitoring between January 2004 and June 2010. Two consultants inde-pendently read all EEGs and reported their findings. Exclusion criteria:abnormal interictal EEG, mental retardation, resistance to antiepilepticdrugs. 509 seizures were evaluated in 71patients.

Result: All the patients had generalized epileptiform discharges. FocalEEG abnormalities were noted in 45% cases. Video-EEG monitoringcaptured focal features of seizures in 15.5% of patients. All patients didnot respond to traditional therapy and became seizure-free after treatmentwith ADEs appropriate for absence or myoclonic seizures.

Conclusion: This study supports the hypothesis of a more continuoustransition between focal and generalized epilepsies in contrast to the pres-ent concept of a stringent pathophysiologic dichotomy. The diagnosis ofIGEs is very demanding for patients with atypical features with regard toseizure type, EEG findings, and response to appropriate AEDs.

p833EPILEPSY IN PATIENTS WITH CEREBRAL PALSY ISNOT ALWAYS LIFELONG CONDITIONP. Ignjatovic, and N. J. JovicClinic of Neurology and Psychiatry for Children and Youth,Belgrade, Serbia

Purpose: The aim of the study was to analyze the clinical prognosis andoutcome of epilepsy in children and young adults with cerebral palsy (CP).

Method: This retrospective study included 61 subjects with CP (52 withspastic form and 9 with mixed form) and epilepsy, both genders, agedfrom 5 to 32 years (mean 14) followed for mean 8.5 years (range 3–15).

Result: Thirty-nine % of studied children had their first seizure withinthe first 12 months of life. Infantile spasms occurred in 13% and 75% of

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these patients later developed focal seizures. Fifty-six % had one seizuretype, 41% had two, while 3% developed three types of seizures. Focalseizures with or without secondary generalization were the most commontypes. Cognitive impairment has been found in 69%. Intractable epilepsydeveloped in 26% of patients, predominantly in children with severe toprofound mental retardation and with serious ambulatory disability. After3–10 years of seizure freedom, antiepileptic drugs (AEDs) were discon-tinued in 13 patients. Sixty-two % of this group remained seizure-freewithout AED treatment for at least 1 year, but 38% had recurrences. Sta-ble remission without AED was achieved in 5 of 6 children with spasticdiplegia, 2 of 5 patients with spastic hemiparesis and in one of two sub-jects with mixed CP form.

Conclusion: Complete seizure control was achieved in three-quarters ofchildren with CP and epilepsy. Almost two-thirds of patients with termi-nal remission remained seizure-free after AED discontinuation. Patientswith spastic diplegia showed the lowest recurrence rates.

p834COMORBIDITY IN CHILDHOOD EPILEPSY IN CLINI-CAL PRACTICEA. Garcia Ron*, R. Blanco Lago*, C. Rodriguez Riero*,J. Herreros Rodriguez�, L. Ballesteros Plaza*, and M. A. De LaMorena Vicente�

*Hospital Universitario Infanta Cristina, Madrid, Spain; and�Hospital Infanta Cristina, Madrid, Spain

Purpose: There are few studies about comorbidity in childhood epi-lepsy. Our objective was to analyze the neurological, psychiatric and sys-temic diseases in children with epilepsy, in outpatients of neuropediatrica level II hospital.

Method: We reviewed medical records of children with epilepsy with atleast a year of follow up. Patients with febrile seizures and acute symp-tomatic seizures were excluded We collected demographic data, comor-bidity, drug responsiveness, visits to emergency department visits andunplanned consultations to pediatric neurologist for seizures.

Result: We include 46 patients, 28.3% had systemic diseases (respira-tory, cardiology, traumatology, endocrinology, otorhinolaryngology dis-eases, chronic infectious diseases). While 41.3% had neurological and/orpsychiatric disorders (neurodevelopment disorders, attention deficithyperactivity disorder, conduct disorder). Having account of childrenwith drug resistant epilepsy: 100% had neurological and/or psychiatricdisorders and 54.5% systemic comorbidities. With respect to the unex-pected visits to emergency room or neurology office by seizures, at leastonce during the follow up: 32.6% of all the patients. In patients with neu-rological/psychiatric and systemic comorbidities this values are 52.6%and 61.5% respectively.

Conclusion: In our study all the patients with drug resistant epilepsyassociated neurological and/or psychiatric pathology. More than a quar-ter of the children presented other chronic medical diseases. Around sixtypercent of epileptic children with systemic pathology consulted at leastonce by seizures in the follow up. It's need develop prospective studiesabout if systemic diseases had influenced in management and prognosisof epilepsy in this population

p835A GENOMIC DELETION ENCOMPASSING KCNQ2CAUSES INFANTILE EPILEPSY: A FURTHER EXAM-PLE OF GENOTYPE AND PHENOTYPE CORRELA-TIONA. P. Parker*, I. Simonic*, and F. L. Raymond�

*Addenbrooke's Hospital, Cambridge, UK; and �University ofCambridge, Cambridge, UK

Purpose: To describe a kindred with deletion of the KCNQ2 gene, ahighly variable phenotype and correlation with loss, rather than alterationof function.

Method: We describe the genetic analysis of chromosome 20q13.33 inan infant with a severe, infantile epilepsy and affected family memberswithout epilepsy.

Result: The proband developed focal convulsive seizures associatedwith apnoea at three weeks of age. Ictal EEG demonstrated low ampli-tude fast activity bilaterally, with evolution over the right centrotemporalregion. Over the next weeks the seizures occurred frequently and she sub-sequently had status epilepticus. Her development and neurologicalexamination have remained normal. With topiramate and clobazam ther-apy her seizure frequency reduced. Aged 15 months she has been seizurefree for 6 months. She received extensive investigation for an epilepticencephalopathy, all of which was normal, with the exception of arrayCGH. This revealed a 216kb genomic deletion using Affymetrix Gene-Chip 6.0 SNP array. The deletion includes the KCNQ2 gene. Furtherinvestigation in the family showed this to be familial but non penetrant infirst and second degree relatives.

Conclusion: The variability in severity of the infantile epilepsies associ-ated with KCNQ2 has been reported to be due to mutation type. This kin-dred further demonstrates that loss of function mutations can be benignand associated with minimal clinical phenotype, or with a severe epilepsyin the neonatal/infantile period which remits over the first year.


p836EVALUATION OF HEALTH CARE UTILISATIONAMONG ADULT PATIENTS WITH EPILEPSY IN THEDISTRICT OF MARBURG-BIEDENKOPF IN GERMANYA. Strzelczyk, T. Nickolay, S. Bauer, A. Haag, S. Knake, W.H. Oertel, P. S. Reif, J. P. Reese, R. Dodel, F. Rosenow, and H.M. HamerPhilipps-University Marburg, Marburg, Germany

Purpose: Epilepsy is a common neurological disorder and imposes asubstantial burden on individuals and society as a whole. We performed across-sectional cohort study in adults with epilepsy irrespective of seizureseverity, duration of illness and epilepsy syndrome. Patients seeking out-patient or inpatient treatment in all health care sectors in the district ofMarburg-Biedenkopf were evaluated in 2008.

Method: During a four month period 366 residents with epilepsy wereenrolled in the study. Costs of inpatient and outpatient treatment werederived from billing data of participating hospitals and office-based phy-sicians. Data on socioeconomic status, course of epilepsy and furtherdirect and indirect costs were recorded using patient questionnaires.

Result: Annual epilepsy-specific costs were estimated to be 7.738 € perpatient, while direct costs constituted 31.1% of the total costs and indirectcosts comprised 68.9%. Direct medical costs were mainly due to hospi-talization (33.2% of total direct costs) and anticonvulsants (26.7%). Costsof admissions were due to status epilepticus (24.4%), video-EEG moni-toring (14.8%), newly diagnosed patients (14.4%) and seizure-relatedinjuries (8.8%). Indirect costs were mainly due to early retirement(38.0%), unemployment (35.9%) and off-days due to seizures (26.2%).

Conclusion: The results highlight the social impact of epilepsy that ismainly due to indirect costs. Hospitalization and medication contributedthe most to the direct costs. Mean costs of epilepsy in this German popu-lation-based study were lower than in studies conducted at European epi-lepsy centers due to inclusion of all health care sectors.

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p837THE KNOWLEDGE ABOUT EPILEPSY HAS SIGNIFI-CANT IMPACT ON QUALITY OF LIFE IN PEOPLEWITH EPILEPSYS. Lee, and Y. Kim, D; Study Group of Knowledge AboutEpilepsyAsan Medical Center, Seoul, Korea

Purpose: Although PWE's knowledge about epilepsy has been thoughtto have an influence on their self-efficacy and quality of life (QoL), therehas been no evidence in the literature.

Method: Data were collected from 572 adult PWE (47.9% male, meanage: 35.8 years, range: 18–69 years) in 31 secondary or tertiary hostpitalsin Korea. Clinical information was obtained by neurologists and the otherinformation was collected using self-completed questionnaires includingEpilepsy Knowledge Profile-General (EKP-G) and Personal (EKP-P),Epilepsy Disclosure Scale, Hospital Anxiety Depression Scale, StigmaScale, Drug Compliance Scale, Impact of Epilepsy Scale, Epilepsy Self-efficacy Scale and Quality of Life in Epilepsy-10 (QOLIE-10).

Result: Higher level of general knowledge (EKP-G, mean: 21.9 range:3–33) was significantly correlated with higher drug compliance(p=0.015) and higher self-efficacy (p<0.001). But it was not linked toQoL. In contrast, higher level of personal knowledge (EKP-P, mean: 2.8,range: 0–8) was significantly related to higher self-efficacy (p<0.001),lower level of depression (p=0.001), and higher mental health of QOLIE-10 (p=0.000). Multivariate analysis showed two predictors for bettermental health of QOLIE-10: higher level of personal knowledge andlower level of depression. Higher level of self-efficacy did not reach sta-tistical significance (p=0.061). In statistical analyses, age, sex, education,economic status, employment status, seizure frequency, epilepsy type,and number of antiepileptic drug were adjusted.

Conclusion: The level of knowledge about epilepsy had significant influ-ences on self-efficacy, drug compliance, depression, and mental health ofHRQOL. Especially, personal knowledge about epilepsy was significantand independent predictor for mental health of HRQOL in PWE.

p838THE UPTAKE AND KNOWLEDGE OF THE UK EPI-LEPSY AND PREGNANCY REGISTRY AMONGSTHEALTHCARE PROFESSIONALS AND PATIENTSJ. R. Howells*, J. Craig�, B. Irwin�, J. Morrow�, andK. Hamandi�

*Cardiff University, Cardiff, UK; �Belfast Health and SocialCare Trust, Belfast, UK; and �University Hospital of Wales,Cardiff, UK

Purpose: Congenital malformation rates associated with antiepilepticdrugs (AEDs) are provided by epilepsy and pregnancy registries. Weaimed to evaluate the uptake and knowledge of the UK epilepsy and preg-nancy registry and assess recent publications from the registry to determinetheir affect on the prenatal management of women with epilepsy (WWE).

Method: Mixed method study. Uptake was defined as the number ofWWE that enrolled onto the registry divided by the estimated UK birthsto WWE. Questionnaires were distributed to 1,300 health care profes-sionals (HCP) via email membership mailing lists and 650 WWE underthe care of the epilepsy unit at University Hospital of Wales by post.

Result: We estimated 30,333–40,480 UK births were to WWE between1996 and 2009; 7,528 women joined the epilepsy pregnancy registrywithin this time period, giving an uptake 18.6–24.8%. In our question-naire 72 (5.5%) HCPs replied; including consultant neurologists, epi-lepsy nurse specialists, GPs and local midwives. 61(84.7%) were awareof the UK registry and 44 (61.1%) had previously referred or advisedWWE to join. 127 (19.5%) questionnaires were returned from WWE,

82.7% (n=105) were unaware of the registry. Of those who'd been eligi-ble to join, only 7 (12%) of respondents had previously done so.

Conclusion: Key publications have resulted from epilepsy pregnancyregistries that guide prescribing trends and pre-conceptual counselling.There is scope to increase uptake of WWE onto the UK registry, byincreasing awareness amongst HCPs and WWE. This is particularlyimportant given the introduction of new anti-epileptic drugs were preg-nancy outcome data are currently limited.

p839HEALTH RELATED QUALITY OF LIFE AND SOCIALSTIGMA IN PATIENTS WITH EPILEPSYM. Prieschl, I. Unterberger, G. Walser, M. Bergmann,G. Kuchukhidze, C. Gneiss, and G. LuefMedical University Innsbruck, Innsbruck, Austria

Purpose: Epilepsy has many non-medical effects on people with epi-lepsy, their family and the community. The aim of our study is to identifyindividual limitations, social stigma and impact on quality of life, profes-sional life and in social interaction due to epilepsy.

Method: A standardized questionnaire (PESOS) was applied to evaluatesocio-demographic aspects, epilepsy specific data and individual prob-lems of patients with epilepsy. Patients were included with a diagnosis ofepilepsy (based on the International classification of epileptic seizures,epilepsies and epileptic syndromes of the League against Epilepsy), aged‡18 years, seen at the University Hospital Innsbruck within one year.

Result: Two hundred patients between 18 and 77 years (mean 42 y; +/)15 y) were included out of an equivalent gender distribution (51%female, 49% male). Epilepsy diagnoses are composed of generalized sei-zures in 21% and focal seizures in 79%. Fortunately 68% valued theirquality of life between 7 and 10 (scale: 0–10) and 57% were seizure freein the last six month. A negative significant correlation (a=0.01) betweenseizure frequency and overall quality of life as well as in the impairmentdue to epilepsy was observed. Discrimination due to epilepsy wasreported in 30% of all patients, especially in the field of professional life(57%) and concerning driving (21%).

Conclusion: Optimal seizure control is essential for long term care ofpatients with epilepsy. However, impaired quality of life and stigma is amajor issue in patients with epilepsy. This study confirms the need forroutine screening, counseling and psychosocial support for patients withepilepsy.

p840HEATH-RELATED QUALITY OF LIFE (HRQOL) INRUSSIAN ADULT PATIENTS WITH EPILEPSYA. Guekht, E. Melikian, L. Milchakova, A. Lebedeva, andI. BondarevaRussian National Reaearch Medical University, Moscow,Russian Federation

Purpose: The aim of this study was to evaluate the changes in HRQOLin the Russian population of patients depending on seizure frequencyreduction (SF) on treatment.

Method: The HRQOL was evaluated by QOLIE-31 (Cramer, 1998)questionnaire, completed by 139 patients with epilepsy, mostly recentlydiagnosed, with different focal or generalized epilepsy syndromes (age(M/SD) 33.27/14.22 years; range 18–74) at the initiation of treatment andin six months.

Result: Overall QOLIE-31 scores in the Russian population, both atbaseline and in follow-up, were lower, then reported from a number ofEuropean countries (Picot et al., 2004; Haritomeni et al., 2006; Tlusta etal., 2008). Compared to baseline, statistically significant changes in theoverall scores were observed in the seizure-free patients (n=60) (M/SD)

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(from 42.19/4.19 to 52.72/3.94), and in patients with more than 50% SFreduction (from 42.67/5.04 to 48.07/4.77)(n=31). Changes in patientswith less than 50% SF reduction (n=22) and patients with no improve-ment (n=26) were not statistically significant. In a multivariate analysis,SF was the significant predictor of the total score and major QOLIE-31domains: seizure worry; overall QOL, energy/fatigue, cognitive func-tioning, medication effects, social functioning.

Conclusion: Seizure frequency in the Russian population is an impor-tant determinant of the total score and major QOLIE-31 domains. How-ever, the overall QOLIE-31 scores are lower, than reported from anumber of European countries, even in seizure –free patients.

p841KNOWLEDGE AND ATTITUDE OF NIGERIAN ADULTSIN AN URBAN CENTERB. Ezeala-Adikaibe, and A. U. JustinUniversity of Nigeria Teaching Hospital, Nigeria

Purpose: To determine the knowledge and attitude of Nigerian adults inan urban center.

Method: This study was cross-sectional and descriptive in design.

Result: A total of 244 subjects who were 30 years and above were inter-viewed. All had previous knowledge of epilepsy, 16.4% had relativeswith epilepsy, 67.2% knew someone with epilepsy and 84.8% had seenconvulsion in the past. About 61.1% and 34.8% agreed that loss of con-sciousness and jerking of the body were some of the manifestations ofseizures. Those who considered epilepsy to be due to witchcraft/demons/charms were 31.6% and 18.9% as a psychiatric disorder. Only 33.6%accepted orthodox medicine as the only treatment and 10.7% herbalistsand 17.6% prayers. During seizures 39.3% would put objects into themouth and 10.7% would run away. Though 61.5% would make friendswith someone with epilepsy, however 73.3% would not marry them.

Conclusion: There is still low level of knowledge and negative attitudeof epilepsy among urban dwellers in south East Nigerian. Concertedefforts should be made to improve the knowledge and attitude of the pop-ulace and improve the social and economic issues affecting people livingwith epilepsy.

p842RISK FACTORS OF EPILEPSY AND CLINICAL-ELEC-TROENCEPHALOGRAPHICAL CORRELATION INCHILDREN WITH PERVASIVE DEVELOPMENTALDISORDERSK. A. Polatynska*, L. Kepczynski�, and J. Wendorff**Polish Mothers’ Memorial Research Institute, Lodz, Poland;and �Medical University of Lodz, Lodz, Poland

Purpose: The aim was to evaluate the correlation between neurologicalsigns and symptoms in children with pervasive developmental disordersand occurrence of paroxysmal activity and epileptiform discharges in dif-ferent areas assessed in EEG examination as well as epilepsy risk factorassessment.

Method: 86 patients with pervasive developmental disorders wereincluded. The correlation between clinical symptoms and electrophysio-logical findings were assessed using Cohrane-Armitage v2 test. Risk fac-tors of epilepsy was assessed by calculating OR. The p-value < 0.05 wastreated as significant.

Result: We have identified significant positive correlation betweenoccurrence of paroxysmal activity and epileptiform discharges in fronto-centro-temporal area and decreasing eye contact, decreasing level offunctioning and number of words. Delayed motor development and intel-lectual disability in higher level than mild, abnormal muscle tone anddelivery by caesarian section were significant risk factors.

Conclusion: The occurrence of epileptiform discharges and paroxysmalactivity is more frequent in children presenting more severe condition,regardless of epileptic seizures. Further investigation of brain electroac-tivity in patients with autism spectrum disorders is inevitable and possi-ble prophylactic treatment in patient not manifesting epileptic seizuresshould be concerned.

p843ICTAL UNILATERAL HYPERKINETIC PROXIMALLOWER LIMB MOVEMENTS – AN INDEPENDENTLATERALISING SIGN SUGGESTING IPSILATERALSEIZURE ONSETR. Teotonio*, B. Diehl�, A. W. Mcevoy�, J. Duncan�, and T. Wehner�

*UCL Institute of Neurology, London, UK; �National Hospitalfor Neurology and Neurosurgery, London, UK; and �TheNational Hospital for Neurology and Neurosurgery, London, UK

Purpose: Our aim was to determine the lateralizing value of ictal unilat-eral hyperkinetic proximal lower limb movements.

Method: We reviewed all patients who underwent intracranial EEGbetween 2008 and 2011 at our centre and whose seizures included hyper-kinetic features. We analyzed seizures for the presence of unilateralhyperkinetic proximal lower limb movements that lasted at least threeseconds and their correlation with electroencephalographic ictal onsetand association with other possible lateralizing signs.

Result: Among 16 patients with ictal hyperkinetic features, three hadunilateral proximal lower limb movements (combination of flexion/extension and ab/adduction in the hip, usually with tonic extension in theknee), sometimes associated with ‘‘hemiballic-like’’ movements of theipsilateral upper limb. There were no other consistent lateralising signs.In all three patients, these movements were ipsilateral to the ictal onsetzone and always started few seconds after electroencephalographic sei-zure onset (2 to 10 seconds). In two patients, intracranial EEG showed aparietal lobe seizure onset. One of them did not proceed to surgery due toclose proximity of the ictal onset zone to eloquent cortex. The otherpatient became seizure free following resection of the left inferior parietallobule (pathology cortical dysplasia type 2B). In the third patient, amesial temporal ictal onset was recorded. The patient ultimately becameseizure free for the past six month after anterior temporal lobe resection(pathology hippocampal sclerosis).

Conclusion: Our results suggest that ictal hyperkinetic proximal lowerlimb movements may be an independent lateralizing sign to the ipsilateralhemisphere.

p844ICTAL AND POSTICTAL SPEECH IMPAIRMENT INTEMPOROBASAL EPILEPSY: AN UNDERRECOG-NIZED CLINICAL MANIFESTATIONR. Toledano Delgado, I. G. Morales, A. J. Huete, and A. G. ReinHospital Ruber Internacional, Madrid, Spain

Purpose: Besides the classic language areas, the basal temporal lan-guage area (BTLA) and the temporal pole may contribute to the function-ing of the language system. However, it is not known whether these brainareas may have clinical relevance in language impairment during tempo-ral lobe seizures. To clarify this issue we evaluated the speech manifesta-tions of seizures caused by lesions located at the basal aspect of thetemporal lobe.

Method: We reviewed medical history, video-EEG recording and neu-roimaging of patients who had temporal seizures caused by small lesionscircumscribed to the temporobasal region over the last 12 years.

Result: Of a total of 168 patients who had temporal lobe seizures regis-tered in our epilepsy unit, 14 patients (8.3%) had small well-defined

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lesions on MRI located at the BTLA or the basal aspect of the temporalpole (4 right, 10 left). Alteration of speech was only found in patientswith left lesions and consisted mostly of speech arrest as well as alter-ation of receptive language. Despite significant language impairment,memory function seemed preserved in nine patients who showed ade-quate ictal behavior and could recall postictally the inability to speak andunderstand.

Conclusion: In addition to the classic language areas, both the BTLAand the more anterior basal pole cortex may play an important role in lan-guage manifestations during temporal lobe seizures. Recognition of thistype of seizures should prompt the physician to carefully reassess thebasal surface of the temporal lobe looking for small lesions that otherwisecould be missed.

p845SEIZURE RESPONSE DOGS FOR CHILDREN'S NOC-TURNAL SEIZURES: UPDATE ON CONSUMERINVOLVEMENT AND FEASIBILITY STUDYK. Jeavons*, S. Ganesan�, M. Prasad�, N. Hussain�,S. Mordekar�, C. Picton§, A. Brown§, W. P. Whitehouse§, andR. Howson–

*Nottingham University Hospitals, Nottingham, UK; �Leicester;�Sheffield; §Nottingham; and –Support Dogs, Sheffield, UK

Purpose: The National Institute for Clinical Excellence advocates theuse of benzodiazepines for prolonged convulsive seizures. Anecdotalreports suggest that family pet dogs may alert carers to the presence ofseizures. Seizure Response dogs are dogs which have been specificallytrained to alert families to the presence of a seizure in children and theaim of this consumer involvement exercise was to assess the feasibility ofpursuing a clinical trial into the efficacy and reliability of SeizureResponse dogs. Preliminary results were presented at the InternationalLeague Against Epilepsy- UK chapter meeting in 2011.

Method: A convenience sample of parents of children with nocturnalseizures were asked to complete a brief questionnaire about their child'sseizures, emergency medication, and whether they had a dog or wouldconsider having one in the future. Data was entered into Excel and simpledescriptive statistics used.

Result: Completed questionnaires were received by 68 families of chil-dren who had had at least one nocturnal seizure within the preceding year.36/68 (53%) had a rescue medication, such as buccal midazolam, for pro-longed seizures. 22/68 (32%) had a frequency of nocturnal seizures of atleast one a week and 13/68 (19%) had at least one seizure every night.The mean age was 10 years and 1 month, however 41/68 (60%) of carersreported sleeping in the child's room or bed within the preceeding month.48/68 (71%) of families would be interested in being involved with futureresearch in this area.

Conclusion: Families responded positively to the concept of SeizureResponse dogs.

p846AN UNUSUALLY SEVERE PHENOTYPE IN A FAMILYWITH A NOVEL SCN1A MUTATION: FROM GEFS+ TODRAVET SYNDROMEH. Goldberg-Stern*, Z. Afawi�, S. Aharoni*, O. Bennett�,S. Appenzeller§, A. Baumgart§, L. Basel-Vanagaite–,G. Kuhlenbaumer§, A. D. Korczyn�, and I. Helbig§

*Schneider Children's Medical Center of Israel, Petach Tikva,Israel; �Sackler Faculty of Medicine, Tel Aviv University, TelAviv, Israel; �Hadassah-Hebrew University Medical Center,Jerusalem, Israel; §Univeristy Medical Center Schleswig-Holstein, Kiel, Germany; and –Raphael Recanati GeneticsInstitute, Petach Tikva, Israel

Purpose: Mutations in SCN1A may cause various epilepsy syndromesincluding generalized epilepsy with febrile seizures plus (GEFS+), a usu-ally mild generalized epilepsy and Dravet Syndrome, a severe epilepticencephalopathy of infancy. Both entities are usually distinct and Dravetsyndrome is rarely seen in GEFS+ families. We describe the clinical andmolecular findings in a large GEFS+ family with a heterogeneous, butunusually severe familial phenotype.

Method: A large GEFS+ pedigree with 13 affected individuals was phe-notyped and genetic analysis for SCN1A was performed.

Result: In the presented GEFS+ family, two infants from differentbranches had classic Dravet syndrome and borderline Dravet Syn-drome (SMEB), respectively. Various Febrile Seizure Plus (FS+) phe-notypes were present in all other affected family members. A novelA fi G missense mutation in exon 21 in SCN1A resulting in a lysineto glutamine change was found in the proband with Dravet Syndrome,and her father who had childhood febrile seizures but is otherwiseunaffected, in her 8-month-old as yet asymptomatic brother and in theSMEB case.

Conclusion: The findings in this family confirm previous observationsof marked intrafamilial clinical variability in GEFS+, but the overallfamilial epilepsy spectrum is more severe than usually observed. Wehypothesize that certain SCN1A mutations may result in more severefamilial GEFS+ phenotypes in conjunction with modifier genes toexplain the observed phenotypic heterogeneity. In these families, the riskof severe epilepsy including Dravet Syndrome may be significantlyhigher than usually seen in GEFS+, resulting in profound implicationsfor genetic counseling.

p847ELECTRIC SOURCE IMAGING (ESI) IN PRESURGICALEPILEPSY INVESTIGATIONS: DENSE ELECTRODECONFIGURATIONS AND SUFFICIENT COVERAGE OFTHE TEMPORAL LOBES IS NECESSARY FOR COR-RECT RESULTSG. Lantz, M. Terrill, T. Gilbert, P. Luu, A. Bunnenberg, D. TuckerElectrical Geodesic Inc, Eugene, Oregon, USA

Purpose: In Electric Source Imaging (ESI) correct source localizationsrequire both a sufficient number of recording electrodes and adequatespatial coverage of the head surface. New EEG systems now allowrecording with up to 256 surface electrodes. In this study we comparedthe localization accuracy of epileptic spikes recorded with 256 electrodesto that with sparser, incomplete or uneven electrode coverage.

Method: In four patients with intracranially verified temporal lobe epi-lepsy, the ictal onset location in 3D was determined in the intracranialelectrodes. Interictal spikes recorded with 256 electrodes were averaged.To determine the importance of spatial sampling density a regular down-sampling of the averaged spike was performed to 128, 64 and 32 electro-des. The importance of sufficient coverage of all areas was assessed bytaking out electrodes in the lower temporal areas. With a distributedsource model (LAURA) the source maximum was localized with boththe original 256 channel and the downsampled spikes, and the localiza-tions were compared to the intracranial ictal onset.

Results: Both regular downsampling and reduced temporal lobe cover-age resulted in a clear deterioration of the ESI results. The most correctsource localizations with respect to the intracranial ictal onset wereobtained with the 256 channel setup.

Conclusion: In order to obtain optimal results with ESI both a densesampling on the head and a sufficient coverage of the lower temporalareas is necessary. Improvement of the results can be obtained at least upto 256 electrodes.

Acknowledgement: This project was supported by Electrocal GeodesicInc.

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Epilepsia Epicongress

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