EPILEPSY

By dr. Yustiani Dikot, Sp.S(K)

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 EPILEPTOGENESIS• Asynchronous 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 seizures• Clonic seizures• Tonic seizures• Tonic clonic seizures• Atonic seizures• Unclassified seizures

Simplified Classification of Epileptic SeizuresPartial seizures• Simple – preservation of awarness• Complex – impairment of consciousnesss• Secondary generalizedGeneralized 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 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 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

Diagnosis• Interviews with patients or witness

– Circumstances surrounding the attacks idiopathic and generalized

No seizure worningNo underlying brain lesionsAssociated with a family history– Symptomatic and localization related

AuraSpecific 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 :HyperventilationPhotic stimulationsSleep deprivation

EEG

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 treatmentImportance of compliance Side effects

Surgical treatmentProposed 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

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

• 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 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 childrenSeizure type First line Second line Third lineTonic-clonic Sodium valproate

CarbamazepineLamotrigine*Oxcarbazepine*

Phenytoin

Myoclonic Sodium valproate Lamotrigine* ClobazamPhenobarbital

Tonic Sodium valproate Lamotrigine* ClobazamTopiramate

Absence Sodium valproate Lamotrigine*Ethosuximide

Clobazam

PartialCarbamazepinePhenytoin

Sodium valproateGabapentinOxcarbazepine*

Lamotrigine*VigabatrinClobazamTopiramate

Infantile spasms VigabatrinCorticosteroids

Sodium valproateNitrazepam

Lamotrigine*

Lennox-Gastaut Sodium valproate Lamotrigine*Topiramate

ClobazamFelbamate

Status Epilepticus

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

Some Reasons for Failure of MonotherapyWrong diagnosis• Syncope, cardiac arrhythmia, etc.• Malingering, pseudoseizures• Underlying neoplasmWrong drug(s)• Inappropriate for seizure type• Kinetic / dynamic interactionsWrong dose• Too low (ignore target range)• Side effects preventing dose increaseWrong patient• 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 :

surgeryInstitution

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