EPILEPSY

Yustiani Dikot

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

Causes of Epilepsy:
Category Cryptogenic/ Idiopathic Symptomatic vascular alcohol crb tumour Persentage 61 Comment 83% age 0-9y 38% age >60 49% age >60 27% 30-39 1% age <30 19% 50-59 11% age>60 3 2 7

15 6 6

Trauma Infection Other

Aetiology of epilepsy
Inherited genetic Epilepsy alone Epilepsy and other neurological manifestation Acquired Trauma Neurosurgery Infection Vascular diseases Hippocampal sclerosis Tumours Neurodegenerative disorders Metabolic disorders,toxic disorders,Miscellaneus,Demyelinating diseases

Congenital (inherited or acquired) Cortical dysplasia/dysgenesis Cerebral tumours Vascular malformations Prenatal injury

Epilepsy alone: Benign familial neonatal convulsion Benign familial infantile convulsion Juvenile myoclonic epilepsy Familial frontal lobe epilepsy Idiopathic generalize epilepsy

Epilepsy with other manifestation

Chromosomal abnormality With myoclonic epilepsy and cerebral degeneration. With extrapyramidal feature. With muscular dystrophy and and mental subnormality With mental subnormality Neurocutaneus syndrome With intermittent disturbances:porphyria Other inherited conditions with neurological and systemic manifestations.

Congenital anomalies
Tuberous sclerosis Storage diseases

Birth trauma
Intracranial haemorrhage

Genetic epilepsies

Cerebral tumours

Intracranial Infections Febrile Seizures

Head Injuries

Hypoxia

Drugs and

Cerebrovascular degenerations

Hypoglycaemia
Hypocalcaemia

alcohol

10 20 Age (years)

60

Factors lowering seizure threshold

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

Occasional
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

Diagnosis

Circumstances surrounding the attacks

idiopathic and generalized No seizure warning 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 video camera and continuos 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

EEG

EEG

EEG

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

Structural lesion

MRI

MRI

MRI

CT Scan
CT Scan should be repeated periodically : Suspicion of a tumor 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

DIFFERENTIAL DIAGNOSIS
Migraine Transient Ischemic Attacks Hyperventilation Tics Myo-clonic Hemi-facial spasm Syncope Sleep disorders Non Epileptic Attacks Narcolepsy Metabolic disorders Transient global amnesia

Management
Medical treatment : Establish a correct diagnosis of epilepsy seizure type and epilepsy syndrome Decide treatment with epileptic drugs is necessary Decide which drug should be used Patients and their family should receive counseling 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 mono-therapy 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 poly-pharmacy 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 Absence

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

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

Myoclonic
Partial

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 Tonic Absence First line Sodium valproate Carbamazepine Sodium valproate Sodium valproate Sodium valproate Carbamazepine Phenytoin Second line Lamotrigine* Oxcarbazepine* Lamotrigine* Lamotrigine* Lamotrigine* Ethosuximide Sodium valproate Gabapentin Oxcarbazepine* Sodium valproate Nitrazepam Lamotrigine* Topiramate Third line Phenytoin Clobazam Phenobarbital Clobazam Topiramate Clobazam Lamotrigine* Vigabatrin Clobazam Topiramate Lamotrigine* Clobazam Felbamate

Partial

Infantile spasms Vigabatrin Corticosteroids Lennox-Gastaut Sodium valproate

Some Reasons for Fail of Mono-therapy

Wrong diagnosis Syncope, cardiac arrhythmia, etc. Malingering, pseudo-seizures 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 tapering off in six month. Normal EEG.

Prognosis
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 and cognitive problem : -Label of epilepsy racial disadvantage -Depends on location, 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

STATUS EPILEPTICUS
Definition:
Prolonged seizures :Epileptic activity 30 min or more. Repetitive attacks without recovery in between.

Classification of status epilepticus:

Dependent on age, seizures type, underlying aethiology and underlying pathophysiology.

Etiology of status epilepticus:

Non epileptic patients: Epileptic petients

 Prolonged or recurrent tonic-clonic seizures persist for 30 minutes or more. Incidence: 18 28 /100000 persons.

TONIC CLONIC STATUS EPILEPTICUS

Occurs most commonly in children, people with learning difficulties, structural cerebral pathology

Aethiology:
Non epileptic :
Acut cerebral events: infections, cerebral injury, CVD, cerebral tumour, acut toxic and metabolic disturbances, febrile convulsions.

Epileptic:Presipitated by drug withdrawal, intercurrent illness, metabolic disturbance,

Cerebral Changes in Status Epilepticus

Status Epilepticus Phase I

Status Epilepticus Phase II

Status Epilepticus Treatment

STAGE OF STATUS EPILEPTYCUS

Premonitory stages:
Epileptic activity increases in frequency and severity-warning of impending status. Therapy at this stages can prevent SE.

Status epilepticus:
Discrete tonic- clonic seizures, the motor activity continuous . Sometimes a progressive changes in the EEG.

PHYSIOLOGIC CHANGES IN STATUS EPILEPTICUS

Phase I: Phase of compensation
Cerebral metabolism markedly increased.
Massive increased of cerebral blood flow. Systemic and cerebral lactate levels rise. Endocrine changes result hyperglicaemia. Blood pressure rises. Massive autonomic activity. Epinephrine and norepinephrine release.

 Phase II: Phase of decompensation: Compensatory physiological mechanisms begin to fail as seizures activity continues.
Cerebral autoregulation breaksdown progressively, seizures related autonomic and cardiorespiratory changes develop hypotention,hypoxia and cardiac dysrithmia. Rise intracranial pressure and systemic hypotention result cerebral oedema. Metabolic and endocrine disturbances :acidocis.hypoglycaemia,hyponatremia and hypokalemia,acut tubular necrosis,renal failure, DIC, Persistent convulsive movement can presipitate rhabdomyolysis.

THE MANAGEMENT OF TONICCLONIC STATUS EPILEPTICUS

General measures:
Cardioraspiratory function:
Airway secure and resuscitation if necessary. Emergency investigation.
Blood test ECG

Monitoring

Emergency drug treatment.

To stop the convulsion Correction of the complications.

Intensive care and seizures monitoring.

DRUG TREATMENT
Premonitory stage:
Diazepam 10 mg i.v.or rectally,if status continues,repeated after 15 minutes or Lorazepam 4 mg bolus,If seizures continues>

Stages of early status:

Lorazepam 4 mg I,v,bolus.If status continues after 30 minutes

Stages of established status

 Stages of established status:

Phenitoin iv infusion of 15 mg/kg,rate 50 mg/min,if status continues after 30 -60 minutes

Stages of refractory status:

General anaesthesia with either:
Propofol 2 mg/kg iv bolus,followed by continues infusion of 5 10 mg/kg/h innitially ,reducing to1 3 mg/kg/h,when seizures have been controlled for 12h,slowly tappered over 12 h,or Thiopental:100 250 mg iv bolus over 20 s ,with further 50 mg boluses every 2 3 minutes until seizure are controlled,followed by a continues iv infusion 3 5 mg/kg/h to maintain a burst suppression pattern on the EEG.Should be slowly withdrawn 12 h after the last zeisure.

 EPILEPSY PARTIALIS CONTINUA: Spontaneous regular or irregular clonic muscle jerk, confined to one part of the body and continuing for hours, days or weeks, there are many potential causes.

COMPLEX PARTIAL S E : Prolonged epileptic episode, fluctuating or frequently recurring result in a confusional state.
Absence status: Typical: Non convulsive status, occuring in the syndrome of idiopathic generalized epilepsy. Atypical absence: Status that occurs in secondary generalized epilepsy of the Lennox Gestaut type.