CLINICAL OF EPILEPSY

Dr. ASHARI BAHAR, M.Kes.,Sp.S.,FINSDEPARTMENT OF NEUROLOGY

FACULTY OF MEDICINEUNIVERSITY OF HASANUDDIN

MAKASSAR

DEFINITIONSDEFINITIONS

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 EPIDEMIOLOGY OF SEIZURES AND EPILEPSYAND 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 ILAE CLASSIFICATION OF SEIZURESCLASSIFICATION OF SEIZURES

Seizures

Partial Generalized

Simple Partial

Complex Partial

Secondarily Generalized

Absence

Myoclonic

Atonic

Tonic

Tonic-ClonicILAE – International League Against Epilepsy

ILAE ILAE CLASSIFICATION OF SEIZURESCLASSIFICATION OF SEIZURES

Seizures

Partial Generalized

Simple Partial

Complex Partial

Secondarily Generalized

ILAE ILAE CLASSIFICATION OF SEIZURESCLASSIFICATION OF SEIZURES

Seizures

Partial Generalized

Simple Partial

With somatosensoryor special sensory symptoms

With motor signs

With autonomic symptoms or signs

With psychic or experiential symptoms

Complex Partial SeizuresComplex 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 SeizuresSecondarily 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 ILAE CLASSIFICATION OF SEIZURESCLASSIFICATION OF SEIZURES

Seizures

Partial Generalized

Absence

Myoclonic

Atonic

Tonic

Tonic-Clonic

Typical Absence SeizuresTypical 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 SeizuresAtypical 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 SeizuresMyoclonic 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 SeizuresTonic and Atonic SeizuresTonic seizuresSymmetric, 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 fallsWhen milder produces head nods or jaw drops.

Consciousness usually impairedDuration - usually seconds, rarely more than 1 minuteEEG – sudden diffuse attenuation or generalized polyspike-wave

Seizures

Partial Generalized

Tonic

AtonicAtonic

Generalized Tonic-Clonic SeizuresGeneralized 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 SyndromesEpilepsy Syndromes

Epilepsy SyndromeGrouping of patients that share similar:– Seizure type(s) – Age of onset– Natural history/Prognosis– EEG patterns– Genetics– Response to treatment

Epilepsy SyndromesEpilepsy SyndromesEpilepsyEpilepsy

PartialPartial GeneralizedGeneralized

IdiopathicIdiopathic SymptomaticSymptomatic IdiopathicIdiopathic SymptomaticSymptomatic

Hippocampal AnatomyHippocampal Anatomy

From Chang and Lowenstein, 2003From Chang and Lowenstein, 2003

Basic Mechanisms Underlying Seizures Basic Mechanisms Underlying Seizures and Epilepsyand Epilepsy

Basic Mechanisms Underlying Basic Mechanisms Underlying Seizures and EpilepsySeizures 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. Babb TL, Brown WJ. Pathological Findings in Epilepsy. In: Engel J. Jr. Ed. Surgical Treatment of the Epilepsies. New York: Raven Press 1987: 511-540Surgical Treatment of the Epilepsies. New York: Raven Press 1987: 511-540 ..

Epilepsy—Basic NeurophysiologyEpilepsy—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 NeurophysiologyEpilepsy—Basic Neurophysiology

Major Neurotransmitters in the brain:

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

hormones

Epilepsy—GlutamateEpilepsy—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—GABAEpilepsy—GABA Major inhibitory neurotransmitter in the CNS Two types of receptors

– GABAA—post-synaptic, specific recognition sites, linked to CI- channel

– GABAB —presynaptic autoreceptors that reduce transmitter release by decreasing calcium influx, postsynaptic coupled to G-proteins to increase K+ current

Cellular Mechanisms of Seizure GenerationCellular 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 FunctionNormal CNS Function

Excitation Inhibition

glutamate,aspartate GABA

Modified from White, 2001

Hyperexcitability reflects both increased Hyperexcitability reflects both increased excitation and decreased inhibitionexcitation and decreased inhibition

Excitation

Inhibition

GABA

glutamate,aspartate

Modified from White, 2001

EXCITATION INCREASEEXCITATION INCREASE

SEIZURESEIZURE

EPILEPSY- A CRITICAL BALANCEEPILEPSY- A CRITICAL BALANCE

INHIBITION DECREASEINHIBITION DECREASE

SEIZURESEIZURE

•NaNa+ + channel antagonistschannel antagonists•CaCa2+2+ channel antagonists channel antagonists•Glutamate receptor antagonistsGlutamate receptor antagonists

•GABAGABAAA agonists agonists•Enhanced GABA levelsEnhanced GABA levels•KK++ channels modulators channels modulators

Synaptic Factors Modifying Neuronal Synaptic Factors Modifying Neuronal ExcitabilityExcitability

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 Non-synaptic (Extrinsic) Factors Modifying Neuronal ExcitabilityNeuronal Excitability

Changes in extracellular ion concentration

Changes in extracellular space

Modulation of transmitter metabolism or uptake by glial cells

Mechanisms of Generating Hyperexcitable NetworksMechanisms 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 Timm Stain Showing Mossy Fiber SproutingSprouting

Timm stain Timm stain (black) for (black) for mossy fiber mossy fiber terminals terminals containing zinccontaining zinc

Chang and Lowenstein, 2003

Hippocampal Circuit Changes With Hippocampal Hippocampal Circuit Changes With Hippocampal SclerosisSclerosis

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

EpileptogenesisEpileptogenesis

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 EpilepsyCauses of Acquired Epilepsy• Severe head injury

• Cerebral hemorrhage

• Brain tumor

• CNS infection

• ? Early life febrile seizures

Development of acquired epilepsyDevelopment of acquired epilepsy

Development of acquired epilepsyDevelopment of acquired epilepsy

Possible Mechanism of Delayed Possible Mechanism of Delayed EpileptogenesisEpileptogenesis

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)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 Etiology of Seizures and EpilepsyEpilepsy

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 EpilepsyEtiology 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 abuseCVD

0 8020 40 60Age (years)

ETIOLOGY OF EPILEPSY BY AGE (ADAPTED FROM NASHEF)

Questions Raised by a First Questions Raised by a First SeizureSeizure

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 SeizureEvaluation 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 PrecipitantsSeizure 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.)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 Metabolic abnormalities and seizuresseizures

Type Comment

HyponatremiaOsmotic 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 pumpHyperthyroidism

May exacerbate epilepsy but rarely is de novo cause

BS = blood sugar.

Seizure Precipitants (cont.)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:

BupropionTricyclics

NeurolepticsPhenothiazinesClozapine

Theophylline Isoniazid Penicillins Cyclosporin Meperidine

Seizure Precipitants (cont.)Seizure Precipitants (cont.)

EEG AbnormalitiesEEG 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 AbnormalitiesEEG Abnormalities

Interictal

left temporal

sharp wave

consistent with a

diagnosis of

partial epilepsy

of left temporal

origin

EEG AbnormalitiesEEG Abnormalities

Interictal generalized

polyspike-wave complex

consistent with a

diaganosis of idiopathic

generalized epilepsy

Medical Treatment of First Medical Treatment of First SeizureSeizure

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 DrugsChoosing Antiepileptic DrugsConsiderations: Seizure typeEpilepsy syndromeEfficacyCostPharmacokinetic profileAdverse effectsPatient’s related medical conditions

(ie beneficial or deleterious effects on co-morbid conditions)

Choosing Antiepileptic DrugsChoosing Antiepileptic DrugsLimited placebo-controlled trials available,

particularly of newer AEDsSeveral 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 DrugsChoosing Antiepileptic DrugsBroad-Spectrum Agents

ValproateFelbamateLamotrigineTopiramateZonisamideLevetiracetamRufinamide*Vigabatrin

Narrow-Spectrum Agents

Partial onset seizuresPhenytoinCarbamazepineOxcarbazepineGabapentinPregabalinTiagabineLacosamide*

AbsenceEthosuximide

* * New AEDs (approved 2008) categorization may changeNew AEDs (approved 2008) categorization may change

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

Best evidence and FDA Indication:Valproate, Topiramate Also shown to be effective:Zonisamide, LevetiracetamPhenytoin, Carbamazepine (may exacerbate absence and myoclonic sz )

Lamotrigine (may exacerbate myoclonic sz of symptomatic

generalized epilepsies)

Choosing Antiepileptic Drugs (cont.)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.)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.)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 MonotherapyAntiepileptic Drug Monotherapy

Simplifies treatment

Reduces adverse effects

Conversion to monotherapy– Eliminate sedative drugs first– Withdraw antiepileptic drugs

slowly over several months

Antiepileptic Drug InteractionsAntiepileptic 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: CommonAdverse Effects of AEDs: CommonTypically 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: SeriousAdverse Effects of AEDs: SeriousTypically Idiosyncratic:

Renal stones topiramate, zonisamide

Anhydrosis, heat stroke topiramate

Acute closed-angle glaucoma topiramate

Hyponatremia carbamazepine, oxcarbazepine

Adverse Effects of AEDs: SeriousAdverse Effects of AEDs: SeriousTypically Idiosyncratic:

Aplastic anemia felbamate, zonisamide, valproate, carbamazepine

Hepatic Failure valproate, felbamate, lamotrigine, phenobarbital

Peripheral vision loss vigabatrin

Rash phenytoin, lamotrigine, zonisamide, carbamazepine

Starting AEDsStarting AEDsDiscuss likely adverse effects

Discuss unlikely but important adverse effects

Discuss likelihood of success

Discuss recording/reporting seizures, adverse effects, potential precipitants

Discontinuing AEDsDiscontinuing AEDs

Seizure freedom for 2 yearsimplies 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 RecurrenceEvaluation 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 Non-Drug Treatment/Lifestyle ModificationsModifications

Adequate sleep

Avoidance of alcohol, stimulants, etc.

Avoidance of known precipitants

Stress reduction — specific techniques

Ketogenic DietKetogenic 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 DietsAlternative 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 SurgeryPatient 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 SurgeryEvaluation for SurgeryHistory 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 TreatmentSurgical 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 SurgeryEpilepsy SurgeryCorpus 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 StimulatorVagus 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 nerveVNS 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 acidValproic acid

Valproic acid , carbamazepine, phenytoinEthozuximideValproic acid Valproic acid Corticotropin

Valproic acid , lamotrigine

Carbamazepine, phenytoin

LamotrigineAcetazolamide, clonazepam, lamotrigine primidoneLamotrigine, phenobarbital,primidoneValproic acid , lamotrigineEthozuximide, clonazepam, Primidone, lamotrigineClonazepam, 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)