epilepsy yitzhak schiller md phd dept of neurology rambam medical center
TRANSCRIPT
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