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Meiti Frida Department of Neurology Andalas University Padang

Abnormal and recurrent excessive synchronized discharge of cerebral neuron with clinical manifestation of epileptic seizure which are an intermittent stereotypical behavior, emotion, motor function or sensation

Paroxysmal depolarization shift (PDS) of the resting membrane potential, which triggers a brief rapid burst of action potentials terminated by a sustained after hyperpolarization PDS : result of imbalance between excitatory (glutamate and aspartate) and inhibitory (GABA) neurotransmitters Abnormalities of voltage controlled membrane ion channels Imbalance between endogenous neuromodulators, acetylcholine favoring depolarization and dopamine enhancing neuronal membrane stability

FOCAL EPILEPTOGENESIS Asynchronous burst firing in some hypocampal and cortical neurons

Generalized epileptogenesis : asynchronous burst firing in abnormal thalamocortical interaction

Developed countries : annual incidence 50-70 cases per 100.000 Developing countries : prevalence 1% Incidence varies with age

Incidence of epilepsy in relation to age

Idiopathic Cryptogenic Symptomatic

Congenital anomalies
Tuberous sclerosis Storage diseases

Birth trauma
Intracranial haemorrhage

Genetic epilepsies

Cerebral tumours

Intracranial Infections Febrile Seizures

Head Injuries


Drugs and

Cerebrovascular degenerations



10 20 Age (years)


Factors lowering seizure threshold

Sleep deprivation Alcohol withdrawal Television flicker Epileptogenic drugs Systemic infection Head trauma Recreational drugs AED non-compliance Menstruation

Barbiturate withdrawal Dehydration Benzodiazepine withdrawal Hyperventilation Flashing lights Diet and missed meals Specific reflex triggers Stress Intense exercise

International Classification of Epileptic Seizures

Partial seizures (beginning locally) Simple partial seizures (without impaired consciousness)
with motor symptoms with somatosensory or special sensory symptoms

Complex partial seizures (with impaired consciousness)

simple partial onset followed by impaired consciousness impaired consciousness at onset

Partial seizures evolving into secondary generalized seizures

Generalized seizures (convulsive or nonconvulsive) Absence seizures

Typical Atypical

Myoclonic seizures Clonic seizures Tonic seizures Tonic clonic seizures Atonic seizures Unclassified seizures

Simplified Classification of Epileptic Seizures

Partial seizures Simple preservation of awarness Complex impairment of consciousnesss Secondary generalized Generalized seizures Absence Myoclonic Tonic-clonic Tonic Atonic

International Classification of Epilepsies and Epileptic Syndrome

Localization-related (focal, local or partial) epilepsies and syndromes Idiopathic epilepsy with age-related onset - benign childhood epilepsy with centrotemporal spikes - chilhood epilepsy with occipital paroxysms Symptomatic epilepsy

Generalized epilepsies and syndromes Idiopathic epilepsy with age-related onset (listed in order of age at onset) - benign neonatal familial convulsions - benign neonatal non-familial convulsions - benign myoclonic epilepsy in infancy - childhood absence epilepsy (formerly known as pyknolepsy) - juvenile absence epilepsy - juvenile myoclonic epilepsy (formerly known as impulsive petit mal) - epilepsy with generalized tonic-clonic seizures on awaking Other idiopathic epilepsies

Idiopathic or symptomatic epilepsy (listed in order of age at onset) - West syndrome (infantile spasms) - Lennox-Gastaut syndrome (childhood epileptic encephalopathy) - epilepsy with myoclonic-astatic seizures - epilepsy with myoclonic absence seizures Symptomatic epilepsy Non-specific syndromes - early myoclonic encephalopathy - early infantile epileptic encephalopathy Specific syndromes (epileptic seizures as a complication of a disease, such as phenylketonuria, juvenile Gauchers disease or Lundborgs progressive myoclonic epilepsy)

Epilepsies and syndromes with both generalized and focal seizures Neonatal seizures Severe myoclonic epilepsy in infancy Epilepsy with continuous spike waves during slow-wave sleep Acquired epileptic aphasia (LandauKleffner syndrome)

Epilepsies without unequivocal generalized or focal features Special syndromes Situation-related seizures - febrile convulsions - seizures related to other identifiable situations, such as stress, hormonal changes, drugs, alcohol withdrawal or sleep deprivation Isolated, apparently unprovoked epileptic events Epilepsies characterized by specific modes of seizure precipitation Chronic progressive epilepsia partialis continua of childhood

Interviews with patients or witness

Circumstances surrounding the attacks


idiopathic and generalized No seizure worning No underlying brain lesions Associated with a family history
Symptomatic and localization related

Aura Specific site of onset Identifiable cause

Recurrent episodes of seizures Symptoms occured during and after seizures

Recording symptomatic events with videocamera and continous ambulatory EEG monitoring

To confirm the clinical diagnosis To support the classification of partial or generalized seizures Routine trace 50% normal Diagnostic in non convulsion state epileptic activities : Hyperventilation Photic stimulations Sleep deprivation



Essential, particularly in partial onset seizures Computerized tomography (CT) Magnetic resonance imaging (MRI)

Structural lesion




Scan should be repeated periodically : Suspicion of a tumour Worsening in neurological examination or cognitive function Deterioration in the frequency or severity of the seizures

Single Photon Emission CT (SPECT) Positron Emission Tomography (PET) MRI spectroscopy Functional MRI

Functional cerebral changes Useful adjuncts in candidate epileptic surgery

Migraine Transient Ischaemic Attacks Hyperventilation Tics Myoclonus Hemifacial spasm Syncope Sleep disorders Non Epileptic Attacks Narcolepsy Metabolic disorders Transient global amnesia

Medical treatment : Establish a correct diagnosis of epileptic seizure type and epileptic syndrome Decide treatment with epileptic drugs is necessary Decide which drug should be used Patients and their families should receive counselling regarding :
Aims of treatment Prognosis and duration of the expected treatment Importance of compliance Side effects

Surgical treatment
Proposed Indications for resective epileptic surgery
Intractable seizures Resectable structural abnormality as identified on magnetic resonance imaging Confirmation that seizures arise from a visible lesion (using video telemetry) Over 20% of seizures arising from the contralateral temporal lobe in temporal lobe seizures Intelligence quotient > 70 points No significant psychiatry morbidity No medical contraindications Age < 45 years

Strategies for managing newly diagnosed epilepsy

Newly diagnosed epilepsy

47% First drug Seizure-free

13% Second drug 40% Refractory Seizure-free

Rational duotherapy

Surgical assessment

Ten commandments in the pharmacological treatment of epilepsy Choose the correct drug for the seizure type or epilepsy syndrome Start at low dosage and increase incrementally Titrate slowly to allow tolerance to central nervous system side-effects Keep the regiment simple with once- or twice-daily dosing, if possible Measure drug concentration when seizures are controlled or if control is not readily obtained (if possible)

Counsel the patient early regarding the implications of the diagnosis and the prophylactic nature of drug therapy Try two reasonable monotherapy options before adding a second drug When seizures persist, combine the best tolerated first-line drug with one of the newer agents depending on seizure type and mechanism of action Simplify dose schedules and drug regimens as much as possible in patients receiving polypharmacy Aim for the best seizure control consistent with the optimal quality of life in patients with refractory epilepsy

Drug choice in newly diagnosed epilepsy in adolescents and adults Seizure type
Tonic clonic

First line
Sodium valproate Carbamazepine Phenytoin
Sodium valproate Sodium valproate Carbamazepine Phenytoin

Second line
Lamotrigine* Oxcarbamazepine*
Ethosuximide Lamotrigine* Lamotrigine* Lamotrigine* Oxcarbamazepine* Sodium valproate Lamotrigine*



Unclassifiable Sodium valproate

*Lamotrigine and oxcarbamazepine are regarded as first-line drugs in some countries

Choice of antiepileptic drugs in children

Seizure type Tonic-clonic Myoclonic First line Sodium valproate Carbamazepine Sodium valproate Second line Lamotrigine* Oxcarbazepine* Lamotrigine* Third line Phenytoin Clobazam Phenobarbital


Sodium valproate
Sodium valproate Carbamazepine Phenytoin

Lamotrigine* Ethosuximide Sodium valproate Gabapentin Oxcarbazepine* Sodium valproate Nitrazepam Lamotrigine* Topiramate

Clobazam Topiramate
Clobazam Lamotrigine* Vigabatrin Clobazam Topiramate Lamotrigine* Clobazam Felbamate


Infantile spasms Vigabatrin Corticosteroids Lennox-Gastaut Sodium valproate

Status Epilepticus
Life threatening medical defined as frequent and / or prolonged epileptic seizure

Some Reasons for Failure of Monotherapy

Wrong diagnosis Syncope, cardiac arrhythmia, etc. Malingering, pseudoseizures Underlying neoplasm Wrong drug(s) Inappropriate for seizure type Kinetic / dynamic interactions Wrong dose Too low (ignore target range) Side effects preventing dose increase Wrong patient Poor compliance with medication Inappropriate lifestyle (e.g. alcohol or drug abuse)

When to stop medication

After 2-3 years period of seizures free, must be tappering off in six month

Dependent with underlying syndrome and / or its cause Patients compliance Reciprocal illness or medications 60-70% controlled by first-line drug of epilepsy 10% of the rest controlled by new drugs The rest : surgery Institution

Special Problems of Epilepsy

Behavioral problem : -Label of epilepsy racial disadvantage -Brain function, medication, type of seizure -Attitudes of helpers and helped Education : -Discussion between doctors, families, schools teachers and the patient, steps which might be taken to promote normal education and personal development

Employment : -Personal and racial states as well as financial reward -Understanding of the employee of their illness in the context of particular employment, safety for their selves and environment -People around in working hours need to know what to do if the attack occurred The law
Driving lisence
Free of seizure after 6 months controlled epilepsy

No permitting to drive if :
Have suffered of epileptic attack at the age before adolescent Medical condition caused driving a source of danger to them selves and to the public

Leisure :
Swimming, water sport, cycling, horse riding in groups with safety controlled Boxing, climbing, sport with body contact are prohibited Television and video games, avoid flickering of the screen

Marriage and pregnancy Health education Impairment, disability and handicap