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Transcript of 1 Pediatric Epilepsy: An Overview and Update on Treatment Options Mitzi Payne, MD Pediatric...
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Pediatric Epilepsy: An Pediatric Epilepsy: An Overview and Update on Overview and Update on
Treatment OptionsTreatment OptionsMitzi Payne, MDMitzi Payne, MD
Pediatric NeurologyPediatric NeurologyMarshall University Marshall University
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Approach to a patient with “spells”Approach to a patient with “spells”
Paroxysmal eventsParoxysmal events
Obtain thorough history:Obtain thorough history:– Before event Before event – Description of event Description of event – After the eventAfter the event
Do descriptions vary event to event?Do descriptions vary event to event?
Are the events epileptic?Are the events epileptic?
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If the “spells” appear to be If the “spells” appear to be epileptic… epileptic…
What type of epileptic seizures?What type of epileptic seizures?
What is the cause of the seizure?What is the cause of the seizure?
Is there a syndrome associated with the Is there a syndrome associated with the seizure type?seizure type?
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““Fits, faints, and funny turns”Fits, faints, and funny turns”11
• Differential Diagnosis of “spells”Differential Diagnosis of “spells”
SyncopeSyncope
MigraineMigraine
Sleep disordersSleep disorders
Pseudoseizures (nonepileptic seizures)Pseudoseizures (nonepileptic seizures)
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Helpful tools for diagnosisHelpful tools for diagnosis
Accurate history and description of eventsAccurate history and description of events
Ask family member to “act out” eventAsk family member to “act out” event
Ask family to videotape eventAsk family to videotape event
Provoking factorsProvoking factors
ElectroencephalogramElectroencephalogram
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Some important pointsSome important pointsClassification(s)Classification(s)– seizure type seizure type an ictal event believed to represent an ictal event believed to represent
a unique pathophysiological mechanism and a unique pathophysiological mechanism and anatomic substrateanatomic substrate
– epilepsy syndrome epilepsy syndrome a complex of signs and a complex of signs and symptoms that define a unique epilepsy symptoms that define a unique epilepsy conditioncondition
Etiological categories of syndromesEtiological categories of syndromes– idiopathic idiopathic no underlying structural brain disease, no underlying structural brain disease,
presumed geneticpresumed genetic– symptomatic symptomatic seizures are the result of lesional or seizures are the result of lesional or
metabolic disease of the brainmetabolic disease of the brain– probably symptomatic (cryptogenic) probably symptomatic (cryptogenic) believed believed
symptomatic but no etiology establishedsymptomatic but no etiology established
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Seizures: focal vs. generalized Seizures: focal vs. generalized
Generalized seizureGeneralized seizure– a seizure whose initial semiology indicates, or is a seizure whose initial semiology indicates, or is
consistent with, more than minimal involvement of consistent with, more than minimal involvement of both hemispheresboth hemispheres
Focal seizure (partial, localization-related)Focal seizure (partial, localization-related)– a seizure whose initial semiology indicates, or is a seizure whose initial semiology indicates, or is
consistent with, initial activation of only part of one consistent with, initial activation of only part of one cerebral hemispherecerebral hemisphere
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Generalized seizure typesGeneralized seizure types
MyoclonicMyoclonic Sudden, <100 ms involuntary contraction of muscle(s) Sudden, <100 ms involuntary contraction of muscle(s) or muscle groupsor muscle groups
ClonicClonic Repetitive, rhythmic myoclonus at 2-3 HzRepetitive, rhythmic myoclonus at 2-3 Hz
TonicTonic Sustained muscle contraction for seconds to minutesSustained muscle contraction for seconds to minutes
Generalized Generalized tonic-clonictonic-clonic
Bilateral symmetrical tonic contraction, then bilateral Bilateral symmetrical tonic contraction, then bilateral clonic contractionsclonic contractions
AtonicAtonic Sudden, brief, 1–2 s decrease in tone without Sudden, brief, 1–2 s decrease in tone without preceding myoclonic or tonic eventpreceding myoclonic or tonic event
AstaticAstatic Loss of posture (=drop) due to atonic, myoclonic, or Loss of posture (=drop) due to atonic, myoclonic, or tonic eventtonic event
SpasmSpasm Axial contraction, may be asymmetricAxial contraction, may be asymmetric
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Generalized epilepsies Generalized epilepsies
Idiopathic Idiopathic generalized generalized epilepsiesepilepsies
Benign myoclonic epilepsy in infancyBenign myoclonic epilepsy in infancyEpilepsy with myoclonic-astatic seizuresEpilepsy with myoclonic-astatic seizuresEpilepsy with myoclonic absence seizuresEpilepsy with myoclonic absence seizuresChildhood absence epilepsyChildhood absence epilepsyIGE with variable phenotypesIGE with variable phenotypes
Juvenile absence, JME, epilepsy with GTC onlyJuvenile absence, JME, epilepsy with GTC onlyGeneralized epilepsies with febrile seizures Generalized epilepsies with febrile seizures
plusplus
Epileptic Epileptic encephalopathiesencephalopathies
Syndromes of infancySyndromes of infancyEarly myoclonic encephalopathy; Ohtahara, Early myoclonic encephalopathy; Ohtahara, Dravet, West syndromesDravet, West syndromes
Lennox-Gastaut syndromeLennox-Gastaut syndromeLandau-Kleffner syndromeLandau-Kleffner syndromeEpilepsy with continuous spike waves in SW sleepEpilepsy with continuous spike waves in SW sleep
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Focal seizure typesFocal seizure types
Focal Focal sensorysensory
with elementary sensory symptomswith elementary sensory symptomswith experiential sensory symptomswith experiential sensory symptoms
Focal Focal motormotor
with elementary clonic motor signswith elementary clonic motor signswith symmetric tonic motor signswith symmetric tonic motor signswith automatismswith automatisms
Secondarily generalized seizuresSecondarily generalized seizures
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EEG Activating Procedures:EEG Activating Procedures:HyperventilationHyperventilation
Deep and regular respirations at a rate of Deep and regular respirations at a rate of 20 / minute for 2 to 4 minutes20 / minute for 2 to 4 minutes
Drop in plasma CO2 by 4-7 ml%Drop in plasma CO2 by 4-7 ml%
Normal response (and best seen in Normal response (and best seen in children) is high amplitude slow activitychildren) is high amplitude slow activity
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EEG Activating Procedures:EEG Activating Procedures:HyperventilationHyperventilation
Hyperventilation may induce diffuse sharp Hyperventilation may induce diffuse sharp waves or spike-wave complexeswaves or spike-wave complexesPatients with generalized epilepsies are most Patients with generalized epilepsies are most likely to have these findingslikely to have these findingsActual seizures can be induced by Actual seizures can be induced by hyperventilationhyperventilation– Absence (petit mal)Absence (petit mal)– Absence (petit mal)Absence (petit mal)– Absence (petit mal)Absence (petit mal)– Temporal lobe seizuresTemporal lobe seizures
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EEG Activating Procedures:EEG Activating Procedures:Intermittent Photic StimulationIntermittent Photic Stimulation
Strobe light flashes (1-30 Hz)Strobe light flashes (1-30 Hz)Photic drivingPhotic driving
Rhythmic activity over the posterior head regionsRhythmic activity over the posterior head regions
Photomyoclonic responsePhotomyoclonic responseRepetitive muscle spikes over the anterior regions of the Repetitive muscle spikes over the anterior regions of the headhead
Photoconvulsive (-paroxysmal) responsePhotoconvulsive (-paroxysmal) responseGeneralized spike and wave complexes Generalized spike and wave complexes
15-20 Hz15-20 Hz
May have jerking or impairment of consciousnessMay have jerking or impairment of consciousness
Photosensitive epilepsiesPhotosensitive epilepsies
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EEG Activating ProceduresEEG Activating Procedures
Somatosensory stimulationSomatosensory stimulationElectrical stimulation of peripheral nervesElectrical stimulation of peripheral nerves
Epileptiform discharges in contralateral Epileptiform discharges in contralateral hemispherehemisphere
Reenactment of a triggerReenactment of a triggerVisual stimulation of geometric patternsVisual stimulation of geometric patterns
Auditory stimulationAuditory stimulation
ReadingReading
HypoglycemiaHypoglycemia
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Infantile spasmsInfantile spasmsWest syndromeWest syndrome
Onset ages 3-12 monthsOnset ages 3-12 months
Brief axial contractions Brief axial contractions – usually bilateral, may be asymmetricalusually bilateral, may be asymmetrical
– typically flexor, may be extensortypically flexor, may be extensor
– usually in clusters, less likely randomusually in clusters, less likely random
– typically on awakening, or when drowsytypically on awakening, or when drowsy
EEG shows hypsarrhythmia EEG shows hypsarrhythmia – multifocal spikesmultifocal spikes
– high voltage, chaotic backgroundhigh voltage, chaotic background
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Infantile spasmsInfantile spasms• ““Symptomatic” casesSymptomatic” cases
– congenital infectionscongenital infections– CNS malformationsCNS malformations– metabolic disordersmetabolic disorders– genetic syndromesgenetic syndromes– tuberous sclerosistuberous sclerosis– perinatal asphyxiaperinatal asphyxia– postnatal trauma postnatal trauma – acquired infectionsacquired infections– immunizationsimmunizations
OftenOften “cryptogenic” “cryptogenic”• no definite cause no definite cause
established but child is established but child is delayeddelayed
RarelyRarely “idiopathic” “idiopathic”• no cause established and no cause established and
child is normalchild is normal
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Infantile spasmsInfantile spasms
Short term treatment to stop spasms, improve Short term treatment to stop spasms, improve EEGEEG– ACTH effective, dose not establishedACTH effective, dose not established
oral steroids not proven effectiveoral steroids not proven effective
– Vigabatrin, especially in tuberous sclerosis Vigabatrin, especially in tuberous sclerosis not available in US, not available in US,
potential retinal toxicitypotential retinal toxicity
Data insufficient to show early treatment or Data insufficient to show early treatment or any treatment changes long term outcome any treatment changes long term outcome
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West SyndromeWest Syndrome
Infantile SpasmsInfantile Spasms
Hypsarrhythmia on EEGHypsarrhythmia on EEG
Developmental regression that begins Developmental regression that begins concurrently with the onset of spasmsconcurrently with the onset of spasms
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Prognosis of West SyndromePrognosis of West Syndrome22
Series of 150 patients with West Series of 150 patients with West Syndrome between 1954 and 1970Syndrome between 1954 and 1970– Idiopathic (n = 44)Idiopathic (n = 44)– Symptomatic (n = 106)Symptomatic (n = 106)
Outcomes measured by school type or Outcomes measured by school type or residence (home or hospital)residence (home or hospital)
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OutcomeOutcome
Idiopathic cases: Idiopathic cases: – Normal school 37%Normal school 37%– Death 6%Death 6%– Other seizure types 43%Other seizure types 43%– Neurologic abnormality 31%Neurologic abnormality 31%
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OutcomeOutcome
Symptomatic cases:Symptomatic cases:– Normal school - noneNormal school - none– Death 37%Death 37%– Other seizure types 59%Other seizure types 59%– Neurological abnormality 65%Neurological abnormality 65%
– Large number progress to develop Lennox Large number progress to develop Lennox Gastaut SyndromeGastaut Syndrome
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Rolandic epilepsyRolandic epilepsyOnset ages 2-12 yrs, peak 5-10 yrsOnset ages 2-12 yrs, peak 5-10 yrs
Characteristic seizuresCharacteristic seizures
Infrequent simple partial seizuresInfrequent simple partial seizures– tingling in mouth, on face, speech arrest tingling in mouth, on face, speech arrest – rare GTCS in sleeprare GTCS in sleep
Resolve by pubertyResolve by puberty
Characteristic EEGCharacteristic EEG– high voltage centrotemporal spikes high voltage centrotemporal spikes – usually bilateralusually bilateral
Imaging normalImaging normal
Considered an idiopathic focal epilepsy Considered an idiopathic focal epilepsy – some evidence for genetic basissome evidence for genetic basis
Treatment Treatment – may not be necessarymay not be necessary– may respond to many drugsmay respond to many drugs
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Centrotemporal spikes in Benign Centrotemporal spikes in Benign Rolandic EpilepsyRolandic Epilepsy
Complex Partial Seizures
• Commonly temporal lobe focus• Begins in one area, then spreads enough
to impair consciousness, but not to evoke a generalized tonic-clonic seizure
• Staring is often part of the initial spread• Also can see automatisms…
Automatisms
• Coordinated involuntary movements• Consciousness impaired• Patient does not recall activity• Simple
– Lip smacking, chewing, uttering sounds, picking, tapping, walking straight or in circles
• Complex (behavior involved)– Undressing, chewing inedible objects,
wandering, aggression
Treatment of complex partial seizures
• Use medications for focal onset seizures– Levetiracetam (Keppra)– Oxcarbamazepine (Trileptal)– Carbamazepine (Tegretol/ Carbatrol)– Lamotrigine (Lamictal)– Topiramate (Topamax)– Zonisimide (Zonegran)– Phenobarbital– Valproic Acid (Depakote)– Lacosamide (Vimpat)
Childhood absence (petit mal) epilepsy
• Peak onset age 4-6 years • Many seizures daily• Seizures last seconds• 70+% have associated automatisms
– eyelid flutter– simple vocalizations– picking movements
• Typical EEG with 3 Hz spike wave• Majority resolve by adolescence
Pathophysiology of Absence Seizures
• Generalized discharges occur from abnormal oscillatory rhythm in thalamocortical circuits
• High density of T-type calcium channels in thalamus, thought to be involved
Treating absence seizures
• Ethosuximide (Zarontin)• Valproic Acid (Depakote)• Lamotrigine (Lamictal)• Levetiracetam (Keppra)
Absence v. Complex Partial Sz
• Absence• < 30 sec• Non-convulsive status
epilepticus• Frequent (100’s a day)• Sudden onset, sudden
termination• No post-ictal state• Hyperventilation a trigger• EEG: 3-4 Hz spike and
wave• Rare interictal
abnormalities
Complex Partial• > 1 minute• Rare non-convulsive
epilepticus• Occur ≤ daily• Frequent simple, complex
automatisms• Evolve to other sz
manifestations• Post-ictal state• EEG: Interictal focal
abnormalities
Behavioral Staring
• Most commonly seen in children with ADD, PDD, MR
• Occurs when “bored” or over-stimulated• Does not typically make the patient fall or
stop an activity abruptly• Can be stopped with close contact /
stimulation• Also can be seen in children with epilepsy!
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Evaluation of a Evaluation of a 11stst unprovoked seizure unprovoked seizure
Good evidence recommends EEG Good evidence recommends EEG – EEG can help diagnose the eventEEG can help diagnose the event
– EEG can identify a specific syndromeEEG can identify a specific syndrome
– EEG can help with prognosisEEG can help with prognosis
– timing of EEG not determinedtiming of EEG not determined
immediate EEG may show abnormality or post immediate EEG may show abnormality or post ictal slowingictal slowing
– abnormal EEG best predictor of recurrence in abnormal EEG best predictor of recurrence in neurologically normal childrenneurologically normal children
– abnormal neuro exam also strong predictor of abnormal neuro exam also strong predictor of recurrencerecurrence
Generalized burst
Benign focal spike
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Evaluation of a Evaluation of a 11stst unprovoked seizure unprovoked seizure
• Insufficient evidence for routine labs, LP, imagingInsufficient evidence for routine labs, LP, imaging– consider emergent imagingconsider emergent imaging
if postictal focal deficit, or not at baseline in several hoursif postictal focal deficit, or not at baseline in several hours
– consider nonurgent MRIconsider nonurgent MRIwith significant neuro abnormalities of unknown etiologywith significant neuro abnormalities of unknown etiology
a seizure of focal onset a seizure of focal onset
in children under 1 year of agein children under 1 year of age
– consider LPconsider LPin the very young child (<6 months)in the very young child (<6 months)
in the patient who fails to return to baselinein the patient who fails to return to baseline
in any patient with meningeal signsin any patient with meningeal signs
if increased ICP suspected, image before LPif increased ICP suspected, image before LP
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How likely is How likely is a 2a 2nd nd seizure?seizure?
Evidence from multiple Class III studiesEvidence from multiple Class III studies
Recurrence ranged from 14%-65%Recurrence ranged from 14%-65%
Most recurrences early (in 1Most recurrences early (in 1stst year) year)
Factors increasing recurrence riskFactors increasing recurrence risk– abnormal EEGabnormal EEG– etiologyetiology
remote symptomatic seizure recurrence >50%remote symptomatic seizure recurrence >50%
idiopathic seizure recurrence 30-50%idiopathic seizure recurrence 30-50%
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Summary of evidence:Summary of evidence:
Treatment of 1Treatment of 1st st unprovoked seizureunprovoked seizure
Most children with a 1Most children with a 1stst seizure have few or no seizure have few or no recurrencesrecurrences
10% will have many seizures regardless of initial Rx10% will have many seizures regardless of initial Rx
Rx after 1Rx after 1stst vs. 2 vs. 2ndnd seizure does not affect long term seizure does not affect long term prognosisprognosis
Rx in adults and children leads to decreased recurrencesRx in adults and children leads to decreased recurrences
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Recommendations:Recommendations:
Treatment of a 1Treatment of a 1stst Seizure Seizure
Anticonvulsant treatment after a 1Anticonvulsant treatment after a 1stst seizure must be seizure must be individualizedindividualized– treatment is not indicated for prevention of epilepsy treatment is not indicated for prevention of epilepsy – treatment may be considered if risks of recurrent seizure out treatment may be considered if risks of recurrent seizure out
weigh risks of Rx weigh risks of Rx
Treatment must take into account patient and family Treatment must take into account patient and family preferencespreferences
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Febrile seizuresFebrile seizuresThe most common seizures in childhoodThe most common seizures in childhood
In US affect 2-4% of children < age 5 yrsIn US affect 2-4% of children < age 5 yrs8% Japan, 14% Guam8% Japan, 14% Guam
1/3 have at least 1 recurrence1/3 have at least 1 recurrence
Risk factors for recurrence Risk factors for recurrence first febrile seizure < 1 year of agefirst febrile seizure < 1 year of age
low degree of fever at first febrile seizurelow degree of fever at first febrile seizure
family history of febrile seizuresfamily history of febrile seizures
brief duration between fever onset and febrile seizurebrief duration between fever onset and febrile seizure
4 risk factors = 70% recurrence 4 risk factors = 70% recurrence
No risk factors = 20% recurrence No risk factors = 20% recurrence
•
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Febrile seizuresFebrile seizures
SimpleSimple– generalized generalized – andand <15 minutes duration <15 minutes duration
ComplexComplex– focalfocal– oror >15 minutes >15 minutes– oror recurrent within 24 hours recurrent within 24 hours
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Evaluation of the child Evaluation of the child with simple febrile seizureswith simple febrile seizures
Lumbar punctureLumbar puncture– if meningeal signsif meningeal signs
– in infants < 12 monthsin infants < 12 months
– with prior antibiotic Rxwith prior antibiotic Rx
Blood studies not needed routinelyBlood studies not needed routinely
Imaging not necessaryImaging not necessary
EEG not necessary in simple febrile seizuresEEG not necessary in simple febrile seizures
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Treatment of the child Treatment of the child with simple febrile seizureswith simple febrile seizures
Effective in reducing recurrences but Effective in reducing recurrences but with potential toxicitieswith potential toxicities– continuous phenobarbital or valproic acidcontinuous phenobarbital or valproic acid– intermittent diazepamintermittent diazepam
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Treatment options for Treatment options for pharmacoresistant epilepsypharmacoresistant epilepsy
Ketogenic dietKetogenic diet
Vagus nerve stimulationVagus nerve stimulation
SurgerySurgery
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Ketogenic dietKetogenic diet Very high fat, very low CHO, Very high fat, very low CHO, minimum RDA proteinminimum RDA protein
Vitamins, mineral supplements Vitamins, mineral supplements necessarynecessary
Rigid compliance essentialRigid compliance essential
Effective in 1/3-1/2 casesEffective in 1/3-1/2 cases– all seizure typesall seizure types– all ages, but easiest to maintain in all ages, but easiest to maintain in
childrenchildren
breakfast
lunch
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Ketogenic diet formulationsKetogenic diet formulationsFormulated in fat:CHO ratiosFormulated in fat:CHO ratios– generally between 4:1 and 3:1generally between 4:1 and 3:1– Atkins diet is about 2.2:1Atkins diet is about 2.2:1
Traditional dietTraditional diet – uses 40% cream, fatty foodsuses 40% cream, fatty foods
MCT dietMCT diet– adds oils to “normal foods”adds oils to “normal foods”
Tube feeding dietTube feeding diet – CHO-free formula + microlipids or CHO-free formula + microlipids or
cooking oilcooking oil
5858
Surgical treatment of epilepsySurgical treatment of epilepsyLobectomyLobectomy– anterior temporal lobectomy most frequent procedureanterior temporal lobectomy most frequent procedure– 70% of selected patients become seizure-free70% of selected patients become seizure-free
Extratemporal resectionExtratemporal resection– nature and extent of pathology determine resultsnature and extent of pathology determine results
Hemispherectomy, multilobar resectionsHemispherectomy, multilobar resections– done in cases with extensive pathologydone in cases with extensive pathology
Corpus callosotomyCorpus callosotomy– rarely performed as sole procedurerarely performed as sole procedure
Multiple subpial transectionsMultiple subpial transections– Palliative, done when focus is in “eloquent cortex”Palliative, done when focus is in “eloquent cortex”
5959
Epilepsy surgery evaluation Epilepsy surgery evaluation (for example)(for example)
Record seizures Record seizures
MRI, MRA, SPECT, PETMRI, MRA, SPECT, PET
Speech and memory testsSpeech and memory tests– Wada testWada test– neuropsych testingneuropsych testing– fMRIfMRI
Electrocorticography, Electrocorticography, intracranial monitoring intracranial monitoring
Brain mappingBrain mapping
SPECT
VideoEEG
Intracranial grid
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Vagus nerve stimulation (VNS)Vagus nerve stimulation (VNS)
FDA approved 1997FDA approved 1997– adjunctive treatment adjunctive treatment
pharmacoresistant partial-pharmacoresistant partial-onset epilepsyonset epilepsy
– ages 12 and olderages 12 and older
Over 25,000 implantedOver 25,000 implanted– 5,000 in children <125,000 in children <12
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Vagus nerve stimulationVagus nerve stimulation
Mild electrical Mild electrical pulses sent to pulses sent to L vagusL vagus
Automatic, Automatic, intermittent stimulationintermittent stimulation
On-demand stimulation with On-demand stimulation with magnetmagnet
In-office programmingIn-office programming
Compliance assuredCompliance assured
Programming
Magnet activation
6262
VNS pulse generator and leadVNS pulse generator and lead>25,000 patients worldwide>25,000 patients worldwide
Model 102 (June 2002) Model 102 (June 2002) – single pin leadsingle pin lead– 6.9 mm thick6.9 mm thick– weight 25 gramsweight 25 grams– 6-11 year battery life6-11 year battery life
Outpatient implantationOutpatient implantation– 1 hour surgery1 hour surgery– device test in OR, activated device test in OR, activated
laterlater
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Seizure-response dogsSeizure-response dogs
How do they do it?How do they do it?
Trained by several Trained by several organizationsorganizations
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Rectal diazepam Rectal diazepam
- - Given for seizures lasting longer than 5 minutesGiven for seizures lasting longer than 5 minutes
- Diastat is a safe way to give rescue seizure medication in - Diastat is a safe way to give rescue seizure medication in the home or school environmentthe home or school environment- Dose varies by age and weight- Dose varies by age and weight- If seizure continues 5 minutes after Diastat given, then - If seizure continues 5 minutes after Diastat given, then EMS should be contactedEMS should be contacted- Some children have seizures that consistently are - Some children have seizures that consistently are prolonged; in the case Diastat may be prescribed to be prolonged; in the case Diastat may be prescribed to be given at onset of seizure, instead of waiting 5 minutes.given at onset of seizure, instead of waiting 5 minutes.- Not FDA approved in children less than 2 years of age- Not FDA approved in children less than 2 years of age
6565
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Other Rescue Medication OptionsOther Rescue Medication Options- - Nasal midazolam - children refractory to DiastatNasal midazolam - children refractory to Diastat- Oral lorazepam - seizure clusters- Oral lorazepam - seizure clusters- Routine seizure medications are NOT given as rescue - Routine seizure medications are NOT given as rescue medications medications - If a child routinely requires rescue medications on a - If a child routinely requires rescue medications on a consistent basis, then routine scheduled seizure consistent basis, then routine scheduled seizure medications need to be changedmedications need to be changed
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