EPILEPSYMeiti Frida

Department of NeurologyAndalas University

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 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 Seizures

Partial seizures Simple – preservation of awarness Complex – impairment of consciousnesss Secondary generalized

Generalized seizures Absence Myoclonic Tonic-clonic Tonic Atonic

Absence Seizure

Atonic Seizure

Focal Seizure

Grandmal Seizure

MioClonic seizure

Tonic Atonic Seizure

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

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 line

Tonic-clonic Sodium valproateCarbamazepine

Lamotrigine*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 Monotherapy

Wrong 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