CLINICAL OF EPILEPSY

Dr. ASHARI BAHAR, M.Kes.,Sp.S.,FINS

DEPARTMENT OF NEUROLOGY
FACULTY OF MEDICINE
UNIVERSITY OF HASANUDDIN
MAKASSAR
DEFINITIONS
 Seizure: the clinical manifestation of
an abnormal, excessive excitation
and synchronization of a population
of cortical neurons

 Epilepsy: recurrent seizures (two or
more) which are not provoked by
systemic or acute neurologic insults
EPIDEMIOLOGY OF SEIZURES AND
EPILEPSY
 Seizures
–Incidence: 80/100,000 per year
–Lifetime incidence: 9%
(1/3 febrile convulsions)

 Epilepsy
–Incidence: 45/100,000 per year
–Point prevalence: 0.5-1%
–Cumulative lifetime incidence: 3%
ILAE
CLASSIFICATION OF SEIZURES
Seizures
Partial Generalized
Simple Partial
Complex Partial
Secondarily
Generalized
Absence
Myoclonic
Atonic
Tonic
Tonic-Clonic
ILAE – International League Against Epilepsy
ILAE
CLASSIFICATION OF SEIZURES
Seizures
Partial Generalized
Simple Partial
Complex Partial
Secondarily Generalized
ILAE
CLASSIFICATION OF SEIZURES
Seizures
Partial Generalized
Simple Partial
With somatosensory
or special sensory symptoms
With motor signs

With autonomic
symptoms or signs

With psychic or
experiential symptoms
Complex Partial Seizures
 Impaired
consciousness
 Clinical manifestations
vary with site of origin
and degree of spread
– Presence and nature of
aura
– Automatisms
– Other motor activity
 Duration typically < 2
minutes
Seizures
Partial Generalized
Complex
Partial
Secondarily Generalized Seizures
 Begins focally, with or
without focal
neurological symptoms
 Variable symmetry,
intensity, and duration
of tonic (stiffening)
and clonic (jerking)
phases
 Typical duration 1-3
minutes
 Postictal confusion,
somnolence, with or
without transient focal
deficit
Seizures
Partial Generalized
Secondarily
Generalized
ILAE
CLASSIFICATION OF SEIZURES
Seizures
Partial Generalized
Absence
Myoclonic
Atonic
Tonic
Tonic-Clonic
Typical Absence Seizures
 Brief staring spells (―petit
mal‖) with impairment of
awareness
 3-20 seconds
 Sudden onset and
sudden resolution
 Often provoked by
hyperventilation
 Onset typically between
4 and 14 years of age
 Often resolve by 18 years
of age
 Normal development and
intelligence
 EEG: Generalized 3 Hz spike-
wave discharges
Seizures
Partial Generalized
Absence
Atypical Absence Seizures
 Brief staring spells with variably reduced
responsiveness
 5-30 seconds
 Gradual (seconds) onset and resolution
 Generally not provoked by hyperventilation
 Onset typically after 6 years of age
 Often in children with global cognitive
impairment
 EEG: Generalized slow spike-wave complexes
(<2.5 Hz)
 Patients often also have Atonic and Tonic
seizures
Myoclonic Seizures

Epileptic Myoclonus
 Brief, shock-like jerk of a
muscle or group of muscles
 Differentiate from
benign, nonepileptic
myoclonus (e.g., while
falling asleep)
 EEG: Generalized 4-6 Hz
polyspike-wave discharges
Seizures
Partial Generalized
Myoclonic
Tonic and Atonic Seizures
Tonic seizures
Symmetric, tonic muscle contraction of
extremities with tonic flexion of waist and
neck
Duration - 2-20 seconds.
EEG – Sudden attenuation with
generalized, low-voltage fast activity
(most common) or generalized polyspike-
wave.

Atonic seizures
Sudden loss of postural tone
When severe often results in falls
When milder produces head nods or jaw drops.
Consciousness usually impaired
Duration - usually seconds, rarely more
than 1 minute
EEG – sudden diffuse attenuation or
generalized polyspike-wave
Seizures
Partial Generalized
Tonic
Atonic
Generalized Tonic-Clonic Seizures
 Associated with loss of
consciousness and post-
ictal confusion/lethargy
 Duration 30-120 seconds
 Tonic phase
 Stiffening and fall
 Often associated with ictal
cry
 Clonic Phase
 Rhythmic extremity jerking
 EEG – generalized
polyspikes
Seizures
Partial Generalized
Tonic-
Clonic
Epilepsy Syndromes
Epilepsy Syndrome
Grouping of patients that share
similar:
– Seizure type(s)
– Age of onset
– Natural history/Prognosis
– EEG patterns
– Genetics
– Response to treatment


Epilepsy Syndromes
Epilepsy

Partial Generalized
Idiopathic Symptomatic Idiopathic Symptomatic
Hippocampal Anatomy
From Chang and Lowenstein, 2003
Basic Mechanisms Underlying Seizures
and Epilepsy
Basic Mechanisms Underlying
Seizures and Epilepsy
 Feedback and
feed-forward
inhibition,
illustrated via
cartoon and
schematic of
simplified
hippocampal
circuit

Babb TL, Brown WJ. Pathological Findings in Epilepsy. In: Engel J. Jr. Ed.
Surgical Treatment of the Epilepsies. New York: Raven Press 1987: 511-540.
Epilepsy—Basic Neurophysiology
 Causes of Hyperexcitability:

– excitatory post synaptic potentials (EPSPs)
– inhibitory post synaptic potentials (IPSPs)
– changes in voltage gated ion channels
– alteration of local ion concentrations






Epilepsy—Basic Neurophysiology
 Major Neurotransmitters in the brain:

– Glutamate
– GABA
– Acetylcholine
– Dopamine
– Serotonin
– Histamine
– Other modulators: neuropeptides, hormones






Epilepsy—Glutamate
 The brain’s major excitatory neurotransmitter
 Two groups of glutamate receptors
– Ionotropic—fast synaptic transmission
• Three subtypes – AMPA, kainate, NMDA
• Glutamate-gated cation channels
– Metabotropic—slow synaptic transmission
• G-protein coupled, regulation of second
messengers (cAMP and phospholipase C)
• Modulation of synaptic activity
 Modulation of glutamate receptors
– Glycine, polyamine sites, Zinc, redox site
Epilepsy—GABA
 Major inhibitory neurotransmitter in the CNS
 Two types of receptors
– GABA
A
—post-synaptic, specific
recognition sites, linked to CI
-
channel
– GABA
B
—presynaptic autoreceptors that
reduce transmitter release by decreasing
calcium influx, postsynaptic coupled to G-
proteins to increase K
+
current
Cellular Mechanisms of Seizure Generation
 Excitation (too much)
– Ionic—inward Na
+
, Ca
++
currents
– Neurotransmitter—glutamate,
aspartate

 Inhibition (too little)
– Ionic—inward CI
-
, outward K
+

currents
– Neurotransmitter—GABA
Normal CNS Function
Excitation
Inhibition
glutamate,
aspartate
GABA
Modified from White, 2001
Hyperexcitability reflects both increased
excitation and decreased inhibition
Excitation
Inhibition
GABA
glutamate,
aspartate
Modified from White, IGES, 2001
Modified from White, 2001



EXCITATION INCREASE
SEIZURE
EPILEPSY- A CRITICAL BALANCE
INHIBITION DECREASE
SEIZURE
•Na
+
channel antagonists
•Ca
2+
channel antagonists
•Glutamate receptor antagonists
•GABA
A
agonists
•Enhanced GABA levels
•K
+
channels modulators
Synaptic Factors Modifying Neuronal
Excitability
 Alterations in expression of transmitter
gated ionotropic channels
 Post-translational changes in
neurotransmitter channels
 Remodeling of synapse location or
configuration (deafferentation,
sprouting)
 Changes in gap-junction synaptic
function


Non-synaptic (Extrinsic) Factors Modifying
Neuronal Excitability
 Changes in extracellular ion
concentration

Changes in extracellular space

 Modulation of transmitter
metabolism or uptake by glial cells

Mechanisms of Generating Hyperexcitable Networks
 Excitatory axonal “sprouting”
 Loss of inhibitory neurons
 Loss of excitatory neurons “driving”
inhibitory neurons
 Change in neuronal firing properties
(channelopathies)

Normal Rat Dentate Gyrus Epileptic Rat Dentate Gyrus
Epileptic Human
Dentate Gyrus
Cavazos and Cross, 2006
Timm Stain Showing Mossy Fiber Sprouting
Timm stain
(black) for
mossy fiber
terminals
containing zinc
Chang and Lowenstein, 2003
Hippocampal Circuit Changes With Hippocampal Sclerosis
Longterm Hyperexcitability (Potentiation)
• Synaptic plasticity.
• Change in the nature
of excit & inhib
transmission.
• Recruits participation
NTs & peptides.
• Change in functional &
structural neuron and glia
 epil focus.

Oster, JM, Gutrecht, JA, Gross, PT : Epilepsy and Syncope. In HR, Hones, FH Netter (eds) :
Neurology. Icon Learning system, 2005, p. 264-280.
Cavazos and Cross, 2006
Epileptogenesis
Mechanism of Epileptogenesis :






• Initiating events :
– Head trauma - Hypoxia
– Stroke - Status epilepticus
– Infection - etc.

Schwartzkroin, PA. : Epileptogenesis. In MJ Aminoff, RB. Daroff (eds) : Encyclopedia of the
Neurological Sciences. Vol 2, Amsterdam, 2003, p.288-209.


Causes of Acquired Epilepsy
• Severe head injury

• Cerebral hemorrhage

• Brain tumor

• CNS infection

• ? Early life febrile seizures
Development of acquired epilepsy
Development of acquired epilepsy
Possible Mechanism of Delayed
Epileptogenesis
 Kindling model: repeated subconvulsive
stimuli resulting in electrical after discharges
– Eventually lead to stimulation-induced
clinical seizures
– In some cases, lead to spontaneous seizures
(epilepsy)
– Applicability to human epilepsy uncertain
Electroencephalogram (EEG)
 Graphical depiction of cortical electrical
activity, usually recorded from the scalp.
 Advantage of high temporal resolution but
poor spatial resolution of cortical disorders.
 EEG is the most important
neurophysiological study for the diagnosis,
prognosis, and treatment of epilepsy.
Etiology of Seizures and Epilepsy
 Infancy and childhood
– Prenatal or birth injury
– Inborn error of metabolism
– Congenital malformation

 Childhood and adolescence
– Idiopathic/genetic syndrome
– CNS infection
– Trauma
Etiology of Seizures and Epilepsy
 Adolescence and young adult
– Head trauma
– Drug intoxication and withdrawal*
 Older adult
– Stroke
– Brain tumor
– Acute metabolic disturbances*
– Neurodegenerative

*causes of acute symptomatic seizures, not epilepsy




Tumors, sporadic infections & metabolic dis.
Malignant tumours
Congenital & genetic conditions
HS, trauma, genetic
predisposition
alcohol/drug abuse
CVD
0
80 20 40 60
Age (years)
ETIOLOGY OF EPILEPSY BY AGE
(ADAPTED FROM NASHEF)
Questions Raised by a First Seizure
Seizure or not?
Provoked? (ie metabolic precipitant?)
Seizure type? (focal vs. generalized)
Evidence of interictal CNS dysfunction?
Syndrome type?
Which studies should be obtained?
Should treatment be started?
Which drug should be used?
Evaluation of a First Seizure
 History, physical
 Blood tests: CBC, electrolytes, glucose,
calcium, magnesium, phosphate, hepatic and renal
function
 Lumbar puncture
(only if meningitis or encephalitis suspected and potential for brain
herniation is excluded)
 Blood or urine screen for drugs
 Electroencephalogram (EEG)
 CT or MR brain scan
Seizure Precipitants
 Metabolic and Electrolyte Imbalance
 Stimulant/other proconvulsant
intoxication
 Sedative or ethanol withdrawal
 Sleep deprivation
 Antiepileptic medication reduction or
inadequate AED treatment
 Hormonal variations
 Stress
 Fever or systemic infection
 Concussion and/or closed head injury
Seizure Precipitants (cont.)
Metabolic and Electrolyte
Imbalance
 Low blood glucose
(or high glucose, esp. w/
hyperosmolar state)
 Low sodium
 Low calcium
 Low magnesium
Metabolic abnormalities and seizures
Type Comment
Hyponatremia
Osmotic shifts, disrupted ionic balance,
in anoxia w/ shutdown of Na-K pump
Hypo- or
hyperkalemia
Rare to cause seizure. Sometimes
through hypomagnesemia
Hypo- or
hypercalcemia
Usually other seizures first, such as
tetany or altered consciousness
Hypoglycemia BS <50, disrupted Na/K pump
Hyperthyroidism
May exacerbate epilepsy but rarely is
de novo cause
BS = blood sugar.
Seizure Precipitants (cont.)
Stimulants/Other Pro-convulsant
Intoxication
 IV drug use
 Cocaine
 Ephedrine
 Other herbal remedies
 Medication reduction
Medications that can lower seizure threshold
 Antidepressants:
Bupropion
Tricyclics
 Neuroleptics
Phenothiazines
Clozapine
 Theophylline
 Isoniazid
 Penicillins
 Cyclosporin
 Meperidine

Seizure Precipitants (cont.)
EEG Abnormalities
 Background abnormalities: significant
asymmetries and/or degree of slowing
inappropriate for clinical state or age
 Interictal abnormalities associated with
seizures and epilepsy
– Spikes
– Sharp waves
– Spike-wave complexes
 May be focal, lateralized, generalized
EEG Abnormalities
Interictal
left temporal
sharp wave
consistent with
a diagnosis of
partial epilepsy
of left temporal
origin
EEG Abnormalities
Interictal generalized
polyspike-wave
complex consistent
with a diaganosis of
idiopathic
generalized epilepsy
Medical Treatment of First Seizure
Whether to treat first seizure is controversial
 16-62% of unprovoked seizures will recur within 5 years
 Relapse rate may be reduced by antiepileptic drugs
 Relapse rate increased if:
 abnormal imaging
 abnormal neurological exam
 abnormal EEG
 family history
 Quality of life issues are important (ie driving)
First Seizure Trial Group. Neurology. 1993;43:478–483. [PubMed]
Camfield et al. Epilepsia. 2002;43:662–663. [PubMed]
Choosing Antiepileptic Drugs
Considerations:
Seizure type
Epilepsy syndrome
Efficacy
Cost
Pharmacokinetic profile
Adverse effects
Patient’s related medical conditions
(ie beneficial or deleterious effects on co-morbid
conditions)

Choosing Antiepileptic Drugs
 Limited placebo-controlled trials available,
particularly of newer AEDs
 Several drugs are commonly used for indications
other than those for which they are officially
approved/recommended
 Choice of AED for partial epilepsy depends largely
on drug side-effect profile and patient’s
preference/concerns
 Choice of AED for generalized epilepsy depends on
predominant seizure type(s) as well as drug side-
effect profile and patient’s preference/concerns
Choosing Antiepileptic Drugs
Broad-Spectrum Agents

Valproate
Felbamate
Lamotrigine
Topiramate
Zonisamide
Levetiracetam
Rufinamide*
Vigabatrin

Narrow-Spectrum Agents

Partial onset seizures
Phenytoin
Carbamazepine
Oxcarbazepine
Gabapentin
Pregabalin
Tiagabine
Lacosamide*

Absence
Ethosuximide

*
New AEDs (approved 2008) categorization may change
Choosing Antiepileptic Drugs (cont.)
Monotherapy for Partial Seizures

Best evidence and FDA indication:
Carbamazepine, Oxcarbazepine, Phenytoin, Topiramate
Similar efficacy, likely better tolerated:
Lamotrigine, Gabapentin, Levetiracetam
Also shown to be effective:
Valproate, Phenobarbital, Felbamate, Lacosamide
Limited data but commonly used:
Zonisamide, Pregabalin

Azar NJ and BW Abou-Khalil. Seminars in Neurology. 2008; 28(3): 305-316. [PubMed]



Choosing Antiepileptic Drugs (cont.)
Monotherapy for Generalized-Onset Tonic-Clonic
Seizures

Best evidence and FDA Indication:
Valproate, Topiramate
Also shown to be effective:
Zonisamide, Levetiracetam
Phenytoin, Carbamazepine (may exacerbate absence and myoclonic sz )
Lamotrigine (may exacerbate myoclonic sz of symptomatic generalized
epilepsies)


Choosing Antiepileptic Drugs (cont.)
Absence seizures

Best evidence:
Ethosuximide (limited spectrum, absence only)
Valproate
Also shown to be effective:
Lamotrigine
May be considered as second-line:
Zonisamide, Levetiracetam, Topiramate, Felbamate, Clonazepam

Choosing Antiepileptic Drugs (cont.)
Myoclonic Seizures

Best evidence:
Valproate
Levetiracetam (FDA indication as adjunctive tx)
Clonazepam (FDA indication)

Possibly effective:
Zonisamide, Topiramate


Choosing Antiepileptic Drugs (cont.)
Lennox-Gastaut Syndrome

Best evidence/FDA indication*:
Topiramate, Felbamate, Clonazepam, Lamotrigine, Rufinamide,
Valproate
* FDA approval is for adjunctive treatment for all except clonazepam

Some evidence of efficacy:
Zonisamide, Levetiracetam
Antiepileptic Drug Monotherapy
 Simplifies treatment

 Reduces adverse effects

 Conversion to monotherapy
– Eliminate sedative drugs first
– Withdraw antiepileptic drugs
slowly over several months


Antiepileptic Drug Interactions
 AEDs that may induce metabolism of other drugs:
 carbamazepine, phenytoin, phenobarbital,
primidone
 AEDs that inhibit metabolism of other drugs:
 valproate, felbamate
 AEDs that are highly protein bound:
 valproate, phenytoin, tiagabine
 carbamazepine, oxcarbazepine
 topiramate is moderately protein bound
 Other drugs may alter metabolism or protein
binding of antiepileptic drugs (especially antibiotics,
chemotherapeutic agents and antidepressants)
Adverse Effects of AEDs: Common
Typically dose-related:
Dizziness , Fatigue , Ataxia, Diplopia
 all AEDs

Irritability
 levetiracetam

Word-finding difficulty
 topiramate

Weight loss/anorexia
 topiramate, zonisamide, felbamate

Weight gain
 valproate (also associated with polycystic ovarian syndrome )
 carbamazepine, gabapentin, pregabalin
Adverse Effects of AEDs: Serious
Typically Idiosyncratic:

Renal stones
 topiramate, zonisamide

Anhydrosis, heat stroke
 topiramate

Acute closed-angle glaucoma
 topiramate

Hyponatremia
 carbamazepine, oxcarbazepine





Adverse Effects of AEDs: Serious
Typically Idiosyncratic:

Aplastic anemia
 felbamate, zonisamide, valproate, carbamazepine

Hepatic Failure
 valproate, felbamate, lamotrigine, phenobarbital

Peripheral vision loss
 vigabatrin

Rash
 phenytoin, lamotrigine, zonisamide, carbamazepine
Starting AEDs
Discuss likely adverse effects

Discuss unlikely but important
adverse effects

Discuss likelihood of success

Discuss recording/reporting seizures,
adverse effects, potential
precipitants
Discontinuing AEDs
 Seizure freedom for  2 years
implies overall >60% chance of successful
withdrawal in some epilepsy syndromes
 Favorable factors
– Control achieved easily on one drug at low dose
– No previous unsuccessful attempts at withdrawal
– Normal neurologic exam and EEG
– Primary generalized seizures except JME
– ―Benign‖ syndrome
 Consider relative risks/benefits (e.g., driving,
pregnancy)

Practice parameter. Neurology. 1996;47:600–602. [PubMed]


Evaluation After Seizure Recurrence
 Progressive pathology?
 Avoidable precipitant?
 If on AED
– Problem with compliance?
– Pharmacokinetic factor?
– Increase dose?
– Change medication?
 If not on AED
– Start therapy?

Non-Drug Treatment/Lifestyle
Modifications
 Adequate sleep
 Avoidance of alcohol, stimulants, etc.
 Avoidance of known precipitants
 Stress reduction — specific techniques
Ketogenic Diet
 Main experience with children, especially with
multiple seizure types
 Likely anti-seizure effect of ketosis (beta
hydroxybutyrate), but other mechanisms also
may be responsible for beneficial effects
 Low carbohydrate, adequate protein, high fat
 50% with a >50% seizure reduction
 30% with >90% reduction
 Side effects include kidney stones, weight loss,
acidosis, dyslipidemia
Alternative Diets
 Modified Atkins diet
• 10 g/day carbohydrates to start, fats encouraged
• No protein, calorie, fluid restriction
• 3 reports to date from Johns Hopkins, 1 from South Korea
– 47% all children with >50% seizure reduction
– Studies underway for adults
 Low-glycemic index treatment
• 40-60 g/day low-glycemic carbohydrates
• Portions generally controlled
• Single report from Massachusetts General

Patient Selection for Surgery
 Epilepsy syndrome not responsive
to medical management
– Unacceptable seizure control despite
maximum tolerated doses of 2-3
appropriate drugs as monotherapy

 Epilepsy syndrome amenable to
surgical treatment




Evaluation for Surgery
History and Exam: consistency, localization of seizure onset
and progression
MRI: 1.5 mm coronal cuts with sequences sensitive to gray-
white differentiation and to gliosis
Other neuroimaging options: PET, ictal SPECT
EEG: ictal and interictal, special electrodes
Magnetoencephalography (MEG): interictal, mapping
Neuropsychological battery
Psychosocial evaluation
Intracarotid amobarbital test (Wada)
Surgical Treatment
 Potentially curative
– Resection of epileptogenic region (―focus‖)
avoiding significant new neurologic deficit

 Palliative
– Partial resection of epileptogenic region
– Disconnection procedure to prevent seizure
spread
• Callosotomy
• Multiple subpial transections





Epilepsy Surgery
Corpus Callosotomy
 Palliative surgery for intractable epilepsies with drop attacks
(i.e. Lennox-Gastaut Syndrome)
 Up to 75% have > 75% reduction in atonic seizures
 Risk of disconnection syndromes

Hemispherectomy
 Indicated for catastrophic hemispheric epilepsies, usually presenting in children
(i.e. Rasmussen’s encepalitis, hemimegalencephaly)
 43-79% seizure free (varies by etiology)
 “Functional hemispherectomy” (disconnection without removal) now more
commonly performed

Multiple Subpial Transections
 Cuts horizontal cortical-cortical connections
 Generally reserved for epileptogenic regions in functional cortex

Spencer SS and L Huh. Lancet Neurol. (2008), 525–537. [Pubmed]
Vagus Nerve Stimulator
 Intermittent programmed electrical stimulation of left
vagus nerve
 Option of magnet activated stimulation
 Adverse effects local, related to stimulus
(hoarseness, throat discomfort, dyspnea)
 Mechanism unknown
 Clinical trials show that 35% of patients have a 50%
reduction in seizure frequency and 20% experience a 75%
reduction after 18 months of therapy.
 May improve mood and allow AED reduction
 FDA approved for refractory partial onset seizures and
refractory depression
Vagal nerve stimulation (
VNS ) is a pacemaker – like
device that intermittently
applies electrical
current to the vagus nerve
VNS may have benefical
effects on both mood and
cognition
Several VNS studies in
epilepsy patients have
sugested an improvement in
quality of life and mood
VAGAL NERVE STIMULATION
RISK FACTORS FOR RECURRENCE OF EPILEPTIC SEIZURE
(Sperling, 1997)

Decreased risk Increased risk
* Cause Idiopathic Symptomatic
* Seizure type Generalized Seizure Partial seizure
(61-70% free seizure/thn) (21-28%)

* Family history No Yes,
* EEG Normal Abnormal
(generalized
spike-Wave
pattern)
* Neurologic finding Normal Abnormal
Recurrence rate :
• Single unprovoked seizure : recurrence rate
16 – 61% (40%)
• Menurut penelitian Camfield et.al. : 4
– Partial seizure, abnormal EEG, abnormal
neurologic findings : chance of recurrence 90%
– Generalized seizure, normal EEG, normal
neurologic findings : chance of recurrence 30%
Marshall 2004

The majority of patients with newly-diagnosed
epilepsy respond well to AEDs. Failure to do so may
be due to:

 An incorrect diagnosis of epilepsy
 An inappropriate choice of AED for the epilepsy
syndrome
 Failure to take the prescribed AED
 An underlying cerebral abnormality
 Covert drug or alcohol abuse

TYPE OF SEIZURES AND
EPILEPTIC SYNDROME
FIRST-LINE DRUG SECOND-LINE DRUG
Primary generalized
Absence seizures *
Myoclonic seizures *

Tonic-clonic seizures

Absence (Childhood)
Absence (adolescence)
Juvenile myoclonic epilepsy
Infantil spasms (West’s
syndrome)
Lennox-gastaut syndr.
Partial
Simple partial seizures,
Complex partial seizures
SGTC, and partial epileptic
syndrome

Ethosuximide, valproic acid
Valproic acid 

Valproic acid ,
carbamazepine, phenytoin
Ethozuximide
Valproic acid 
Valproic acid 
Corticotropin 

Valproic acid , lamotrigine

Carbamazepine, phenytoin

Lamotrigine
Acetazolamide, clonazepam,
lamotrigine primidone
Lamotrigine,
phenobarbital,primidone
Valproic acid , lamotrigine
Ethozuximide, clonazepam,
Primidone, lamotrigine
Clonazepam, Valproic acid 

Carbamazepine 

Gabapentin, lamotrigine,
phenobarbital, primidone,
tiagabine, topiramate,
Valproic acid 
* Carbamazepine and phenytoin contraindicated
 Divalproex sodium may be better tolerated than valproic acid
 Vigabatrin may be an alternative first-line drug where available
 Clonazepam, felbamate, phenobarbital, primidone, or vigabatrin may be used alternatively
 Methsuximide may be used alternatively for any of the partial seizures or partial epilepsy syndrome.
SUMMARY (1)
• Several basic principles in the
management of epilepsy
– Accurate diagnosis
– The choice of most effective AED
• Starting with monotherapy
• Continuing with polytherapy
– Beware of the emerging mental problems
• Therapy with AED is recommended :
– To prevent further seizure/single seizure
which tendency to recur
– To the unprovoked seizure

• The succes/failure of treatment depends
on the following factors :
– Accurate diagnosis
– Most effective AED
– Attitude, compliabce, knowledge
– Cooperation of the patient with physician,
paramedies family / relatives
SUMMARY (2)
• When the diagnosis is established :
– Take AED for years
– Started with first line drugs
– Continued with drugs as add on drugs
• Alternative therapy for refractory epileptic
seizure :
– Surgery
– Vagal nerve stimulation
– Ketogenic diat
SUMMARY (3)

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