EPILEPSY

Dr. Hj. Meiti Frida, Sp.S

Bagian Neurologi FK-Unand

RS. DR. M. Djamil Padang

DEFINITION

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

PATHOPHYSIOLOGY

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 EPILEPTOGENESISAsynchronous burst firing in some hypocampal and cortical neurons

Generalized epileptogenesis :

asynchronous burst firing in abnormal

thalamocortical interaction

EPIDEMIOLOGY

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

ETIOLOGY

Idiopathic

Cryptogenic

Symptomatic

Hypoxia

Hypoglycaemia

Hypocalcaemia

Febrile

Seizures

Intracranial

Infections

Birth trauma

Intracranial

haemorrhage

Congenital anomalies

Tuberous sclerosis

Storage diseases

1 5 100 20

Head Injuries

Drugs and

alcohol

Genetic epilepsies Cerebral tumours

60

Cerebrovascular degenerations

Age (years)

Factors lowering seizure threshold

Common Occasional•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 non-convulsive)

Absence seizures• Typical• Atypical

Myoclonic seizuresClonic seizuresTonic seizuresTonic clonic seizuresAtonic 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 epilepsyNon-specific syndromes

- early myoclonic encephalopathy- early infantile epileptic encephalopathy

Specific syndromes (epileptic seizures as a complication of a disease, such as phenylketonuria, juvenile Gaucher’s disease or Lundborg’s 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 (Landau-Kleffner syndrome)

Epilepsies without unequivocal generalized or focal featuresSpecial syndromesSituation-related seizures

- febrile convulsions- seizures related to other identifiable

situations, such as stress, hormonal changes, drugs, alcohol withdrawal or sleep deprivationIsolated, apparently unprovoked epileptic eventsEpilepsies characterized by specific modes of seizure precipitationChronic progressive epilepsia partialis continua of childhood

DiagnosisInterviews with patients or witness

• Circumstances surrounding the attacks idiopathic and generalized

No seizure worningNo underlying brain lesionsAssociated with a family history

• Symptomatic and localization relatedAuraSpecific site of onsetIdentifiable cause

• Recurrent episodes of seizures• Symptoms occured during and after seizures

Recording symptomatic events with videocamera and continous ambulatory EEG monitoring

E E G

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

EEG

BRAIN IMAGING

Essential, particularly in partial onset seizures

Computerized tomography (CT)

Magnetic resonance imaging (MRI)

Structural lesion

MRI

MRI

MRI

ScanScan 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 spectroscopyFunctional MRI

Functional cerebral changes Useful adjuncts in candidate epileptic surgery

DIFFERENTIAL DIAGNOSIS• Migraine

• Transient Ischaemic Attacks

• Hyperventilation

• Tics

• Myoclonus

• Hemifacial spasm

• Syncope

• Sleep disorders

• Non Epileptic Attacks

• Narcolepsy

• Metabolic disorders

• Transient global amnesia

ManagementMedical 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 surgeryIntractable 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

First drug

Second drug

Refractory

Rational duotherapy Surgical assessment

Seizure-free

Seizure-free

47%

13%

40%

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

• 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 First line Second line

Tonic clonic

•Sodium valproate

•Carbamazepine

•Phenytoin

•Lamotrigine*

•Oxcarbamazepine*

Absence •Sodium valproate •Ethosuximide

•Lamotrigine*

Myoclonic •Sodium valproate •Lamotrigine*

Partial

•Carbamazepine

•Phenytoin

•Lamotrigine*

•Oxcarbamazepine*

•Sodium valproate

Unclassifiable •Sodium valproate •Lamotrigine*

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

Choice of antiepileptic drugs in children

Seizure type First line Second line Third line

Tonic-clonic Sodium valproate

Carbamazepine

Lamotrigine*

Oxcarbazepine*

Phenytoin

Myoclonic Sodium valproate Lamotrigine* Clobazam

Phenobarbital

Tonic Sodium valproate Lamotrigine* Clobazam

Topiramate

Absence Sodium valproate Lamotrigine*

Ethosuximide

Clobazam

Partial

Carbamazepine

Phenytoin

Sodium valproate

Gabapentin

Oxcarbazepine*

Lamotrigine*

Vigabatrin

Clobazam

Topiramate

Infantile spasms Vigabatrin

Corticosteroids

Sodium valproate

Nitrazepam

Lamotrigine*

Lennox-Gastaut Sodium valproate Lamotrigine*

Topiramate

Clobazam

Felbamate

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

Poor compliance with medication

Inappropriate lifestyle (e.g. alcohol or drug abuse)

When to stop medication

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

Prognosis

• Dependent with underlying syndrome and / or its cause

• Patient’s compliance

• Reciprocal illness or medications

• 60-70% controlled by first-line drug of epilepsy

• 10% of the rest controlled by new drugs

• The rest :

• neurosurgery department

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