EpilepsyEpilepsy

Epileptic seizures:an abnormal and excessive discharge of brain neurons involving hypersynchrony accompanied by some behavioral change.

Hystory of epilepsyHystory of epilepsy

1. Origin of the name of epilepsy:Epilambano, Epilambanein, EpilepsiaMorbus Sacer, Morbus Lunaticus, DaemonicusEpilepsy

2. Famous persons with epilepsy:Fedor M. Dostoevsky, Gustave Flaubert, Julius Caesar, Vincent van Gogh

A hystorical reviewA hystorical review

• Hippocrates (400 B.C.) „De morbo sacro”• Galen (100 A.D.): first classification• XVIII-XIXth centuries: Tissot (petit mal), Todd

(paresis), Calmeil (absence), H. Jackson(pathophysiology of epilepsy), Gowers (organic and functional epilepsy)

• XXth century: Gibbs at al., Lennox, Jasper(EEG characteristics of the epilepsy), Penfield(electrical stimulations of the neocortex, temporal lobectomy), Gastaut (syndromes)

Definition of epilepsyDefinition of epilepsy

• Epilepsy: – two or more seizures– occur in attacks– the behavioural changes

are usually stereotyped– epileptiform abnormalities

on EEG• Acute and recurrent seizures, status epilepticus, occasional convulsion

• Epilepsy syndrome as a clinical entity

Epidemiology of epilepsyEpidemiology of epilepsy

1. 1. The prevalenceThe prevalence within a particular within a particular population: 0,3population: 0,3 --0,60,6--1,0%. In children: >1%1,0%. In children: >1%

2. Man/woman: 1,12. Man/woman: 1,1 --1,71,73. 3. The incidenceThe incidence : 0,4: 0,4--0,70,7--1,0‰ /year1,0‰ /year4. 4. The chancesThe chances of having at least one of having at least one

seizure during a lifetime: seizure during a lifetime: 88--1010%%

Classification of epileptic seizuresClassification of epileptic seizures

1. Partial (focal, local) seizures1.1. Simple partial seizures

• with motor signs• with somatosensory or special

sensory symptoms• with autonomic symptoms• with psychic symptoms

Classification of epileptic seizuresClassification of epileptic seizures

1.2. Complex partial seizures• Simple partial onset followed by

impairment of consciousness- only with impairment of consciousness

- with automatism• With impairment of consciousness at

onset

Classification of epileptic seizuresClassification of epileptic seizures

1.3. Partial seizures evolving to secondary generalized seizures• Simple partial seizures →→→→• Complex partial seizures →→→→• Simple partial seizures →→→→ Complex

partial seizures →→→→

Classification of epileptic seizuresClassification of epileptic seizures

2. Generalized seizuresAbsence seizures (typical and atypical)Myoclonic seizuresClonic seizuresTonic seizuresTonic-clonic seizuresAtonic (astatic) seizures

3. Unclassified epileptic seizures

Situation-related seizuresSituation-related seizures

• Febrile convulsions• Seizures occurring only with an acute or toxic event, due to factors such as alcohol, drugs, eclampsia, nonketotichyperglycaemia

Pathophysiology and neurobiochemistry of epilepsy

Pathophysiology and neurobiochemistry of epilepsy

� The role of ION channels: Na+, Ca2+, Cl- and GABA receptor system and the glutamate (NMDA) receptors:

carbamazepine, phenytoin has effect on the closing and opening mechanism of the Na-channel prolonging the refractor time.

Pathophysiology and neurobiochemistry of epilepsy

Pathophysiology and neurobiochemistry of epilepsy

�� GABA : The most important inhibitor GABA : The most important inhibitor neurotransmitter of the brain on the neurotransmitter of the brain on the GABA GABA AA--BenzodiazepineBenzodiazepine--PhenobarbitalPhenobarbital-- receptor receptor complexcomplex, controlling the opening and closing , controlling the opening and closing mechanism of the Chloridemechanism of the Chloride--channel.channel.

� GABA B-receptor connects to the K+connects to the K+--ion ion channels and influences the NMDA mediated channels and influences the NMDA mediated excitabilityexcitability ..

Pathophysiology and neurobiochemistry of epilepsy

Pathophysiology and neurobiochemistry of epilepsy

� GABA hypofunction causes seizure. The GABA agonists can protect (valproate, vigabatrin, tiagabine).

� The kindling phenomenon and the mirror focus

Pathophysiology and neurobiochemistry of epilepsy

Pathophysiology and neurobiochemistry of epilepsy

� The role of the substantia nigra (can control the GM seizures)

� The role of sleeping and awakening.

Etiologies of epilepsy and seizuresEtiologies of epilepsy and seizures

1. Genetic factors2. Cerebral infection3. Head trauma4. Cerebrovascular diseases (stroke)5. Brain tumors6. Multiple sclerosis and cerebral

degenerative disease7. Metabolic and toxic agents

Developmental corticalmalformations with epilepsy

Developmental corticalmalformations with epilepsy

• Pachygyria, heterotopia (nodular), lissencephaly

• polymicrogyria, shizencephaly, cortical dysplasia (gliosis),microdysgenesis

Developmental corticalmalformations with epilepsy

Developmental corticalmalformations with epilepsy

2. Malformations due to abnormal neuronal and glial proliferation:microencephaly, non-neoplastic (tuberoussclerosis), neoplastic (ganglioglioma)

3. Neurocutaneous disorders: Sturge-Weber syndrome, neurofibromatosis

4. Others: subarachnoid cyst, porencephaly

Etiologies of epilepsygenetic factors

Etiologies of epilepsygenetic factors

• The concordance rate in monozygotic twins: >70%, in dizygotic twins: 15%

• Genetic factors: 1/5 of adults and 1/3 of children

• Occurrence of epilepsy in relativesIn idiopathic epilepsy: 1.3 - 8%In symptomatic epilepsy: 0.5 - 15% In normal population: 0.5%

Diagnosis of epilepsyDiagnosis of epilepsy

•• Seizures are diagnosed primary by the history (anamnesis, heteroanamnesis)

• Laboratory tests, ECG (Holter), Doppler examination of supraaortic arteries, examination of CSF, toxicology

Diagnosis of epilepsyDiagnosis of epilepsy

EEG: routine, sleep deprivation, photicstimulation, HV, digital analysis of power spectrum, sphenoidalrecording, Holter EEG, split screen EEG (video+EEG)

Diagnosis of epilepsyDiagnosis of epilepsy

• • NeuroimagingCT scan, MRI, SPECT, PET

• Genetic examination• Psychological, psychiatric examination

Nonepileptic paroxysmal disordersNonepileptic paroxysmal disorders

� CardiovascularSyncopeBreath-holding spells (cyanotic, noncyanotic)Mitral valve prolapse

� Cerebrovascular (transient ischemic attack)

� Migraine

Nonepileptic paroxysmal disordersNonepileptic paroxysmal disorders

� Movement disorder

Tics, Tourette’s syndromeMyoclonusChorea and paroxysmal choreoathetosis

Nonepileptic paroxysmal disordersNonepileptic paroxysmal disorders

� Sleep disordersNarcolepsySleep terrors and somnambulismRapid eye movement (REM) sleep disorderBenign sleep jerks Periodic leg movements (nocturnal myoclonus)

Nonepileptic paroxysmal disordersNonepileptic paroxysmal disorders

� Metabolic-toxic (e.g., pheochromocytoma, drug ingestion)

� Gastrointestinal

� PsychiatricPsychogenic seizuresSomatization and dissociative disordersPanic disorderIntermittent explosive disorder Malingering

Therapy of epilepsyTherapy of epilepsy

Sixty-seventy percent of patients are seizure free on AE therapy and another 25 percent’s are decreased

Phytoterápia

Surgical treatment of epilepsySurgical treatment of epilepsy

Ten percent to 15% of patients with refractory seizures may be surgical candidates. The aim of surgery is to remove the focus of origin of the seizures or to prevent spread of the seizure discharge.

Presurgical evaluationPresurgical evaluation

� Patient selection

� Clinical evaluation

� EEG (interictal recordings, ictal recordings to document seizure onset, EEG/video telemetry monitoring is required, intracranial EEG recording: epidural electrodes subdural strip electrodes, IC electrodes)

� Neuroimiging (MRI, SPECT, PET, functional MRI)

� Neuropsychological Psychiatric Assessment

Surgical proceduresSurgical procedures

� Lesionectomy (dysplasia, ganglioma, low grade gliomas, vascular anomalies, neuronal migration, in presence of mesial-temporal sclerosis)

� Selective amygdalohippocampectomy (focal mesio-temporal sclerosis)

Surgical proceduresSurgical procedures

� Anterior temporal lobectomy (amygdala, anterior hippocampus, anterior temporal neocortex)

� Hemispherectomy (Sturge-Weber syndrome, Lennox-Gastaut Syndrome)

� Corpus callosotomy (anterior two-thirds or complete; atonic seizures, Lennox-Gastautsyndromre)

� Multiple subpial transection