epilepsy yitzhak schiller md phd dept of neurology rambam medical center

EpilepsyEpilepsy

Yitzhak Schiller MD PhDYitzhak Schiller MD PhD

Dept of Neurology Rambam Medical CenterDept of Neurology Rambam Medical Center

Lecture planLecture plan

Definitions and pathophysiologyDefinitions and pathophysiology

EpidemiologyEpidemiology

ClassificationClassification

Seizure typeSeizure type

TreatmentTreatment

Definitions and Definitions and pathophysiologypathophysiology

DefinitionsDefinitions

Epileptic seizureEpileptic seizure

EpilepsyEpilepsy

Epileptic seizureEpileptic seizure

Clinical symptoms caused by increased Clinical symptoms caused by increased electrical activity cortical neuronselectrical activity cortical neurons

Epileptic seizures may be caused by Epileptic seizures may be caused by intrinsic or extrinsic factors/causesintrinsic or extrinsic factors/causes

Epilepsy-definitionEpilepsy-definition

Recurrent unprovoked seizuresRecurrent unprovoked seizures

At least two seizures (with a minimal time-At least two seizures (with a minimal time-

delay of 24 hours)delay of 24 hours)

Without an external reversible causeWithout an external reversible cause

Seizures caused by an external reversible Seizures caused by an external reversible

cause-Acute symptomatic seizurescause-Acute symptomatic seizures

PathophysiologyPathophysiology

Increased electrical activity in individual Increased electrical activity in individual neuronsneurons

Synchronized activity between different Synchronized activity between different neurons neurons

Pathophysiological Pathophysiological mechanisms for the mechanisms for the

development of epilepsydevelopment of epilepsy Hyper-excitabile neurons due to mutations in Hyper-excitabile neurons due to mutations in

voltage- and ligand-gated channelsvoltage- and ligand-gated channels ––channelopathieschannelopathies

Decreased inhibitionDecreased inhibition

Alteration of the network-increased connections Alteration of the network-increased connections between neurons due to post-damage axonal between neurons due to post-damage axonal sproutingsprouting

EpidemiologyEpidemiology

Epileptic seizureEpileptic seizure

EpilepsyEpilepsy

Epidemiology-SeizuresEpidemiology-Seizures

IncidenceIncidence80/100,00080/100,000

Life time prevalenceLife time prevalence7 % (3 % F.C.)7 % (3 % F.C.)

Prevalence of Prevalence of epilepsyepilepsy

Incidence of Incidence of epilepsyepilepsy

Classification: Type of Classification: Type of epilepsyepilepsy

GeneralizedGeneralized

Partial-focalPartial-focal

Classification: Cause of Classification: Cause of epilepsyepilepsy

IdiopathicIdiopathic Genetic factorsGenetic factors chennelopathieschennelopathies

SympthomaticSympthomatic CVACVA TumorsTumors Post traumaticPost traumatic

Cryptogenic-remote symptomaticCryptogenic-remote symptomatic

Types of seizures-Types of seizures-Generalized epilepsyGeneralized epilepsy

Generalized tonic clonic seizureGeneralized tonic clonic seizure Absence seizureAbsence seizure Myoclonic jerkMyoclonic jerk Tonic seizureTonic seizure Clonic seizureClonic seizure Atonic seizureAtonic seizureMost patients suffer from several Most patients suffer from several

seizure typeseizure type

Types of seizures-Partial Types of seizures-Partial epilepsyepilepsy

Partial simple seizurePartial simple seizure

Partial complex seizurePartial complex seizure

Secondary generalized tonic-clonic Secondary generalized tonic-clonic seizureseizure

DD-Loss of consciousness DD-Loss of consciousness with/without involuntary with/without involuntary

movementsmovements

Rare etiologiesRare etiologies MigraineMigraine TIATIA Sleep disordersSleep disorders Genetic-metabolic Genetic-metabolic

disordersdisorders

Epileptic seizureEpileptic seizure

Cardio vascularCardio vascular Vaso-vagal Vaso-vagal

syncopesyncope ArrhythmiaArrhythmia Postural Postural

hypotensionhypotension

PsychogenicPsychogenic

Findings supporting Findings supporting epileptic seizuresepileptic seizures

TraumaTrauma

Tongue bitingTongue biting

Loss of urineLoss of urine

Events initiating in sleepEvents initiating in sleep

Other presenting Other presenting forms/syndromes of forms/syndromes of

epilepsyepilepsy Confusion and loss of awareness-Confusion and loss of awareness-

starringstarring

Involuntary movementsInvoluntary movements

ExamsExams

EEGEEG Inter ictalInter ictal IctalIctal

ImagingImaging

EEGEEG

Inter ictal EEG

Inter ictal EEG

Video-EEG monitoring

Ictal EEGIctal EEG

Treatment of epilepsyTreatment of epilepsy

??Should we treatShould we treat

After a single seizure-not necessarilyAfter a single seizure-not necessarily

After two or more seizure-treatAfter two or more seizure-treat

How to treatHow to treat

First line-antiepileptic drugsFirst line-antiepileptic drugs..

Antiepileptic drugs are in fact anti-Antiepileptic drugs are in fact anti-seizure drugs as they prevent seizures seizure drugs as they prevent seizures but do not treat the underline but do not treat the underline pathologypathology

Rarely treatment is provided to treat Rarely treatment is provided to treat the underlying pathologythe underlying pathology

Antiepileptic drugsAntiepileptic drugs

More than 16 available drugsMore than 16 available drugs

Can be divided according to:Can be divided according to: Prevention Vs aborting of prolonged Prevention Vs aborting of prolonged

seizuresseizures Old Vs newOld Vs new General pharmacological mechanismsGeneral pharmacological mechanisms

Old antiepileptic drugsOld antiepileptic drugs

barbituratebarbiturate

HydantoinHydantoin

CarbamazepineCarbamazepine

Valproic acidValproic acid

BenzodiazepinsBenzodiazepins

EthosuxamideEthosuxamide

New antiepileptic drugsNew antiepileptic drugs

Zonisamide (Zonigran)Zonisamide (Zonigran)

))LyricaLyrica(( pregabalinpregabalin TiagabinTiagabin

FelbamateFelbamate

Vigabatrin (Sabrilan)Vigabatrin (Sabrilan)

Lamotrigine (lamictal)Lamotrigine (lamictal)

Gabapentin (Neurontin)Gabapentin (Neurontin)

Oxcarbazepine Oxcarbazepine

(Trileptin)(Trileptin)

Topiramate (Topamax)Topiramate (Topamax)

Levetiracetam (Keppra)Levetiracetam (Keppra)

Antiepileptic drugs-Antiepileptic drugs-Pharmacological Pharmacological

mechanismsmechanisms Modification of voltage-gated sodium Modification of voltage-gated sodium

channelschannels Lamotrigine, Lamotrigine, Carbamazepine, HydantoinHydantoin

Enhanced GABA neurotransmissionEnhanced GABA neurotransmission Barbiturates, Benzodiazepines, VigabatrinBarbiturates, Benzodiazepines, Vigabatrin

Modification of voltage-gated calcium channelsModification of voltage-gated calcium channels

Blockade of AMPA receptorsBlockade of AMPA receptors

UnknownUnknown

How to choose an How to choose an antiepileptic drugantiepileptic drug

EfficacyEfficacy

Adverse eventsAdverse events

Ease of useEase of use

PricePrice

General principlesGeneral principles Partial epilepsy:Partial epilepsy:

Carbamazepine, Lamotrigine, Carbamazepine, Lamotrigine, Topiramate, LevetiracetamTopiramate, Levetiracetam

General epilepsy:General epilepsy: Valproic acid, Lamotrigine, Valproic acid, Lamotrigine, Topiramate Topiramate

Old drugs before new ?Old drugs before new ? Monotherapy when possibleMonotherapy when possible Drugs available IVDrugs available IV

Valproic acid, phenytoinValproic acid, phenytoin

Special considerations-Special considerations-adverse eventsadverse events

Women- teratogenicityWomen- teratogenicity

ChildrenChildren

Elderly populationElderly population

Patients with systemic diseasesPatients with systemic diseases

Status epilepticusStatus epilepticus

ConvulsiveConvulsive30 minutes of continuous seizure or 30 minutes of continuous seizure or recurrent seizure without regaining recurrent seizure without regaining consciousnessconsciousness

Non convulsiveNon convulsive

Focal motorFocal motor

Convulsive status Convulsive status epilepticusepilepticus

Medical emergencyMedical emergency IV Lorazepam or DiazepmIV Lorazepam or Diazepm IV Phenytoin or Fos PhenytoinIV Phenytoin or Fos Phenytoin IV Valproic acidIV Valproic acid IV PhenobarbitalIV Phenobarbital Continuous IV administration of MidazolamContinuous IV administration of Midazolam Continuous IV administration of PropafolContinuous IV administration of Propafol Continuous IV administration of Pentotal-Continuous IV administration of Pentotal-

Pentotal comaPentotal coma

Discontinuation of Discontinuation of treatmenttreatment

Approximately 50% of patients are Approximately 50% of patients are cured with timecured with time

After 2 years of treatment AED After 2 years of treatment AED treatment can be discontinuedtreatment can be discontinued

Under optimal conditions 1/3 of Under optimal conditions 1/3 of patients suffer from seizure patients suffer from seizure recurrence after AED discontinuationrecurrence after AED discontinuation

Prognosis of epilepsyPrognosis of epilepsyFully controlled

on first AED

Fully controlled on AED combination

IntractableDrug-resistant

Pharmaco-resistant Pharmaco-resistant epilepsyepilepsy

Uncontrolled seizures despite Uncontrolled seizures despite appropriate antiepileptic drug appropriate antiepileptic drug treatmenttreatment

30% of all patients with epilepsy30% of all patients with epilepsy

The chance of fuly controling seizures The chance of fuly controling seizures with additional medications is lowwith additional medications is low

Non pharmacological Non pharmacological treatment for pharmaco-treatment for pharmaco-

resistant epilepsyresistant epilepsy Epilepsy surgeryEpilepsy surgery

Ketogenic dietKetogenic diet

Vagal nerve stimulationVagal nerve stimulation

Epilepsy surgeryEpilepsy surgery

Existence of a well defined epileptic Existence of a well defined epileptic

zonezone

The epileptogenic zone was reliably The epileptogenic zone was reliably

localizedlocalized

The epileptogenic zone is located in The epileptogenic zone is located in

a functionally “quit” area a functionally “quit” area

Anterior temporal lobectomy and amygdalo-hippocampectomy

:Surgical outcomeGood correlation between imaging and video-EEG findings

0

10

20

30

40

50

60

70

80

90

100

epilepsy side effects

Seizure free

Seizures

none

memory

severe

גורמים לאפילפסיה גורמים לאפילפסיה סימפטומטיתסימפטומטית

אוטמים מוחייםאוטמים מוחיים5%5%שכיח יותר בדימומים לוברים , שכיח יותר בדימומים לוברים פרכוסים מוקדמים פרכוסים מוקדמים ,

( (15%15%))10%10%.מפתחים אפילפסיה לאחר מאורע מוחי. מפתחים אפילפסיה לאחר מאורע מוחי

חבלת ראשחבלת ראש לאחר חבלת ראש חמורה לאחר חבלת ראש חמורה1717סיכוי לאפילפסיה עולה פי סיכוי לאפילפסיה עולה פי 50%50%פציעה חודרת פציעה חודרת 20%20%דימום סוב דורלי דימום סוב דורלי

Epileptic syndromesEpileptic syndromesJuvenial myoclonic Juvenial myoclonic

epilepsyepilepsyStrong genetic factorsStrong genetic factorsProbably AD with partial penetranceProbably AD with partial penetranceMyoclonic jerks-post sleepMyoclonic jerks-post sleepGTC SzGTC Sz..Absence Sz. In a third of patientsAbsence Sz. In a third of patientsAge of onset 12-18 yearsAge of onset 12-18 yearsSensitive to precipitating factors to Sensitive to precipitating factors to

seizuresseizuresLife time treatment is necessaryLife time treatment is necessary

Epileptic syndromes Epileptic syndromes Lennox GastuatLennox Gastuat

Age of onset 1-8 (3-5) yearsAge of onset 1-8 (3-5) years

Generalized seizures-multiple subtypesGeneralized seizures-multiple subtypes

EEG Slow spike & SWEEG Slow spike & SW

Cognitive impairmentCognitive impairment

Epileptic syndromes-Absence Epileptic syndromes-Absence epilepsyepilepsy

Childhood absence epilepsyChildhood absence epilepsyMultifactorial genetic (10 % in siblings)Multifactorial genetic (10 % in siblings)Age of onset 4-8 yearsAge of onset 4-8 years4040 % % of patients with GTC Szof patients with GTC Sz..Myoclonic jerks ar infrequentMyoclonic jerks ar infrequentAlmost all patients are cured with ageAlmost all patients are cured with age

Juvenial absence epilepsyJuvenial absence epilepsyAge of onset 7-17Age of onset 7-17Genetic factorsGenetic factorsLess frequent absence seizures than in CAELess frequent absence seizures than in CAE8080 % % of patients with GTC Szof patients with GTC Sz..1515 % % with myoclonic jerkswith myoclonic jerksMany are cured but the prognosis is worst than CAEMany are cured but the prognosis is worst than CAE

Epileptic syndromes Epileptic syndromes Benign focal epilepsy of Benign focal epilepsy of

childhoodchildhoodBenign centro-temporal epilepsy of Benign centro-temporal epilepsy of

childhoodchildhood2525 % % of epilepsy at ages of 5-14 yearsof epilepsy at ages of 5-14 yearsFocal seizures facial-mouth movements/jerks, Focal seizures facial-mouth movements/jerks,

speech arrest, hyper-salivation. Jerks in arm speech arrest, hyper-salivation. Jerks in arm or arm+leg is less frequentor arm+leg is less frequent

Secondary GTC seizuresSecondary GTC seizuresTypical EEG findingsTypical EEG findingsUsually spontaneously cureUsually spontaneously cure

Epileptic syndromesEpileptic syndromes--West West syndromesyndrome

Infantile spasmInfantile spasmOther seizures may also occur especially Other seizures may also occur especially

generalized and focal convulsionsgeneralized and focal convulsionsHyps-arrhythmia on EEGHyps-arrhythmia on EEGMay be associated with a developmental delayMay be associated with a developmental delayMay be accompanied by focal neurological May be accompanied by focal neurological

deficitsdeficitsAge of onset 0-2 yearsAge of onset 0-2 years..IS usually disappear up 5 yearsIS usually disappear up 5 years6060 % % symptomaticsymptomaticPrognosis 60 % continue to suffer from Prognosis 60 % continue to suffer from

epilepsy, and 70 % develop MRepilepsy, and 70 % develop MR..

Epileptic syndromesEpileptic syndromesReflex epilepsyReflex epilepsy

Visual trigger most common-Visual trigger most common-photosensitive epilepsyphotosensitive epilepsy

GeneralizedGeneralizedPartial-occipitalPartial-occipital TVTVVideo gamesVideo gamescomputercomputer