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Epilepsy
Yitzhak Schiller MD PhD
Dept of Neurology Rambam Medical Center
Lecture plan
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Definitions and pathophysiology
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Epidemiology
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Classification
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Seizure type
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Treatment
Definitions and pathophysiology
Definitions
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Epileptic seizure
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Epilepsy
Epileptic seizure
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Clinical symptoms caused by increased
electrical activity cortical neurons
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Epileptic seizures may be caused by
intrinsic or extrinsic factors/causes
Epilepsy-definition
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Recurrent unprovoked seizures
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At least two seizures (with a minimal time-
delay of 24 hours)
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Without an external reversible cause
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Seizures caused by an external reversible
cause-Acute symptomatic seizures
Pathophysiology
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Increased electrical activity in individual
neurons
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Synchronized activity between different
neurons
Pathophysiological mechanisms for
the development of epilepsy
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Hyper-excitabile neurons due to mutations in
voltage- and ligand-gated channels –
channelopathies
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Decreased inhibition
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Alteration of the network-increased connections
between neurons due to post-damage axonal
sprouting
Epidemiology
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Epileptic seizure
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Epilepsy
Epidemiology-Seizures
80/100,000
Incidence
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7 % (3 % F.C.)
Life time prevalence
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Prevalence of epilepsy
Incidence of epilepsy
Classification: Type of epilepsy
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Generalized
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Partial-focal
Classification: Cause of epilepsy
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Idiopathic
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Genetic factors
chennelopathies
Sympthomatic
CVA
 Tumors
 Post traumatic
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Cryptogenic-remote symptomatic
Types of seizures-Generalized
epilepsy
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Generalized tonic clonic seizure
Absence seizure
Myoclonic jerk
Tonic seizure
Clonic seizure
Atonic seizure
Most patients suffer from several seizure type
Types of seizures-Partial epilepsy
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Partial simple seizure
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Partial complex seizure
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Secondary generalized tonic-clonic seizure
DD-Loss of consciousness
with/without involuntary movements
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Epileptic seizure
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Cardio vascular
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Vaso-vagal syncope
Arrhythmia
Postural hypotension
Psychogenic
Rare etiologies
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Migraine
TIA
Sleep disorders
Genetic-metabolic
disorders
Findings supporting epileptic
seizures
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Trauma
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Tongue biting
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Loss of urine
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Events initiating in sleep
Other presenting forms/syndromes
of epilepsy
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Confusion and loss of awarenessstarring
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Involuntary movements
Exams
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EEG
Inter ictal
 Ictal

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Imaging
EEG
Inter ictal EEG
Inter ictal EEG
Video-EEG monitoring
Ictal EEG
Treatment of epilepsy
Should we treat ?
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After a single seizure-not necessarily
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After two or more seizure-treat
How to treat
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First line-antiepileptic drugs.
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Antiepileptic drugs are in fact anti-seizure drugs
as they prevent seizures but do not treat the
underline pathology
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Rarely treatment is provided to treat the
underlying pathology
Antiepileptic drugs
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More than 16 available drugs
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Can be divided according to:
Prevention Vs aborting of prolonged seizures
 Old Vs new
 General pharmacological mechanisms
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Old antiepileptic drugs
barbiturate
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Hydantoin
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Carbamazepine
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Valproic acid
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Benzodiazepins
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Ethosuxamide
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New antiepileptic drugs
Zonisamide (Zonigran)
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Vigabatrin (Sabrilan)
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pregabalin (Lyrica)
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Lamotrigine (lamictal)
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Tiagabin
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Gabapentin (Neurontin)
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Felbamate
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Oxcarbazepine
(Trileptin)
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Topiramate (Topamax)
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Levetiracetam (Keppra)
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Antiepileptic drugsPharmacological mechanisms
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Modification of voltage-gated sodium
channels
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Lamotrigine, Carbamazepine, Hydantoin
Enhanced GABA neurotransmission
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Barbiturates, Benzodiazepines, Vigabatrin
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Modification of voltage-gated calcium channels
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Blockade of AMPA receptors
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Unknown
How to choose an antiepileptic drug
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Efficacy
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Adverse events
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Ease of use
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Price
General principles
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Partial epilepsy:
Carbamazepine, Lamotrigine, Topiramate,
Levetiracetam
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General epilepsy:
Valproic acid, Lamotrigine, Topiramate
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Old drugs before new ?
Monotherapy when possible
Drugs available IV
Valproic acid, phenytoin
Special considerations-adverse
events
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Women- teratogenicity
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Children
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Elderly population
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Patients with systemic diseases
Status epilepticus
 Convulsive
30 minutes of continuous seizure or recurrent
seizure without regaining consciousness
 Non
convulsive
 Focal
motor
Convulsive status epilepticus
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Medical emergency
IV Lorazepam or Diazepm
IV Phenytoin or Fos Phenytoin
IV Valproic acid
IV Phenobarbital
Continuous IV administration of Midazolam
Continuous IV administration of Propafol
Continuous IV administration of PentotalPentotal coma
Discontinuation of treatment
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Approximately 50% of patients are cured with
time
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After 2 years of treatment AED treatment can
be discontinued
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Under optimal conditions 1/3 of patients suffer
from seizure recurrence after AED
discontinuation
Prognosis of epilepsy
Fully controlled
on first AED
Intractable
Drug-resistant
Fully controlled on
AED combination
Pharmaco-resistant epilepsy
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Uncontrolled seizures despite appropriate
antiepileptic drug treatment
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30% of all patients with epilepsy
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The chance of fuly controling seizures with
additional medications is low
Non pharmacological treatment
for pharmaco-resistant epilepsy
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Epilepsy surgery
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Ketogenic diet
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Vagal nerve stimulation
Epilepsy surgery
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Existence of a well defined epileptic zone
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The epileptogenic zone was reliably localized
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The epileptogenic zone is located in a
functionally “quit” area
Anterior temporal lobectomy
and amygdalo-hippocampectomy
Surgical outcome:
Good correlation between imaging and video-EEG findings
100
90
80
70
60
50
40
30
20
10
0
Seizure free
Seizures
none
memory
severe
epilepsy
side effects
‫גורמים לאפילפסיה סימפטומטית‬
‫‪‬‬
‫אוטמים מוחיים‬
‫‪ 5% ‬פרכוסים מוקדמים‪ ,‬שכיח יותר בדימומים לוברים (‬
‫‪)15%‬‬
‫‪ 10% ‬מפתחים אפילפסיה לאחר מאורע מוחי‪.‬‬
‫‪‬‬
‫חבלת ראש‬
‫‪ ‬סיכוי לאפילפסיה עולה פי ‪ 17‬לאחר חבלת ראש חמורה‬
‫‪ ‬פציעה חודרת ‪50%‬‬
‫‪ ‬דימום סוב דורלי ‪20%‬‬
Epileptic syndromes
Juvenial myoclonic epilepsy
Strong genetic factors
Probably AD with partial penetrance
Myoclonic jerks-post sleep
GTC Sz.
Absence Sz. In a third of patients
Age of onset 12-18 years
Sensitive to precipitating factors to seizures
Life time treatment is necessary
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Epileptic syndromes
Lennox Gastuat
Age of onset 1-8 (3-5) years
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Generalized seizures-multiple subtypes
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EEG Slow spike & SW
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Cognitive impairment
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Epileptic syndromes-Absence epilepsy
Childhood absence epilepsy
Multifactorial genetic (10 % in siblings)
Age of onset 4-8 years
40 % of patients with GTC Sz.
Myoclonic jerks ar infrequent
Almost all patients are cured with age
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Juvenial absence epilepsy
Age of onset 7-17
Genetic factors
Less frequent absence seizures than in CAE
80 % of patients with GTC Sz.
15 % with myoclonic jerks
Many are cured but the prognosis is worst than CAE
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Epileptic syndromes
Benign focal epilepsy of childhood
Benign centro-temporal epilepsy of childhood
25 % of epilepsy at ages of 5-14 years 
Focal seizures facial-mouth movements/jerks, 
speech arrest, hyper-salivation. Jerks in arm or
arm+leg is less frequent
Secondary GTC seizures 
Typical EEG findings 
Usually spontaneously cure 
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Epileptic syndromes-West syndrome
Infantile spasm 
Other seizures may also occur especially generalized and 
focal convulsions
Hyps-arrhythmia on EEG 
May be associated with a developmental delay 
May be accompanied by focal neurological deficits 
Age of onset 0-2 years. 
IS usually disappear up 5 years 
60 % symptomatic 
Prognosis 60 % continue to suffer from epilepsy, and 70 
% develop MR.
Epileptic syndromes
Reflex epilepsy
Visual trigger most common-photosensitive
epilepsy
Generalized 
Partial-occipital 
TV 
Video games 
computer 
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