Epilepsy Lecture 2007.Revisi

7/29/2019 Epilepsy Lecture 2007.Revisi

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EPILEPSY

Yustiani Dikot


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DEFINITION

Abnormal and recurrent excessive

synchronized discharge of cerebral

neuron with clinical manifestation ofepileptic seizure which are an

intermittent stereotypical behavior,

emotion, motor function or sensation


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PATHOPHYSIOLOGY Paroxysmal depolarization shift (PDS) of the

resting membrane potential, which triggers abrief rapid burst of action potentials terminatedby a sustained after hyperpolarization

PDS : result of imbalance between excitatory(glutamate and aspartate) and inhibitory(GABA) neurotransmitters

Abnormalities of voltage controlled membraneion channels

Imbalance between endogenousneuromodulators, acetylcholine favoringdepolarization and dopamine enhancing

neuronal membrane stability


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FOCAL EPILEPTOGENESIS Asynchronous burst firing in some

hypocampal and cortical neurons


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Generalized epileptogenesis :

asynchronous burst firing in abnormal

thalamocortical interaction


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EPIDEMIOLOGY

Developed countries :

annual incidence 50-70 cases per

100.000

Developing countries : prevalence 1%

Incidence varies with age


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Incidence of epilepsy in relation to age


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ETIOLOGY

Idiopathic

Cryptogenic

Symptomatic


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Causes of Epilepsy:

Category Persentage Comment

Cryptogenic/ 61 83% age 0-9y

Idiopathic 38% age >60

Symptomaticvascular 15 49% age >60

alcohol 6 27% 30-39

crb tumour 6 1% age 60

Trauma 3

Infection 2

Other 7


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Aetiology of epilepsyInherited geneticEpilepsy alone

Epilepsy and other neurological manifestation

Acquired

TraumaNeurosurgery

Infection

Vascular diseases

Hippocampal sclerosis

TumoursNeurodegenerative disorders

Metabolic disorders,toxic disorders,Miscellaneus,Demyelinating diseases


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Congenital (inherited or acquired)

Cortical dysplasia/dysgenesis

Cerebral tumours

Vascular malformations

Prenatal injury


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Epilepsy alone:

Benign familial neonatal convulsionBenign familial infantile convulsion

Juvenile myoclonic epilepsy

Familial frontal lobe epilepsyIdiopathic generalize epilepsy


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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 syndromeWith intermittent disturbances:porphyria

Other inherited conditions with neurological andsystemic manifestations.


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HypoxiaHypoglycaemia

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)


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Factors lowering seizure threshold

Common OccasionalSleep deprivation

Alcohol withdrawal

Television flicker

Epileptogenic drugs

Systemic infection

Head trauma

Recreational drugsAED non-compliance

Menstruation

Barbiturate withdrawal

Dehydration

Benzodiazepinewithdrawal

Hyperventilation

Flashing lights

Diet and missed meals

Specific reflex triggers

Stress

Intense exercise


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Internat ional Class i f icat ion of Ep i lept ic Seizures

Partial seizures (beginning locally)

Simple partial seizures (without impairedconsciousness) with motor symptoms

with somatosensory or special sensory symptoms

Complex partial seizures (with impairedconsciousness) simple partial onset followed by impaired consciousness

impaired consciousness at onset

Partial seizures evolving into secondary generalizedseizures


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Generalized seizures (convulsive or non-convulsive)

Absence seizures Typical

Atypical

Myoclonic seizures

Clonic seizures

Tonic seizures

Tonic clonic seizures

Atonic seizures Unclassified seizures


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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


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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


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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


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Idiopathic or symptomatic epilepsy (listed inorder 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 asphenylketonuria, juvenile Gauchers disease orLundborgs progressive myoclonic epilepsy)


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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)


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Epilepsies without unequivocal generalized orfocal 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 epilepticevents

Epilepsies characterized by specific modes ofseizure precipitation

Chronic progressive epilepsia partialiscontinua of childhood


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Diagnosis Interviews with patients or witness

Circumstances surrounding the attacksidiopathic 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


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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 stimulations

Sleep deprivation


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EEG


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EEG


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BRAIN IMAGING

Essential, particularly in partial onset

seizures

Computerized tomography (CT)

Magnetic resonance imaging (MRI)

Structural lesion


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MRI


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MRI


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MRI


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CT Scan

CT Scan should be repeated

periodically :

Suspicion of a tumor Worsening in neurological examination

or cognitive function

Deterioration in the frequency orseverity of the seizures


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Single Photon Emission CT (SPECT)

Positron Emission Tomography (PET)

MRI spectroscopy

Functional MRI

Functional cerebral changes

Useful adjuncts in candidate epilepticsurgery


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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


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ManagementMedical 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 receivecounseling regarding :

Aims of treatmentPrognosis and duration of the expected

treatment

Importance of compliance

Side effects


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Surgical treatment

Proposed Indications for resective epileptic

surgery Intractable seizures

Resectable structural abnormality as identified onmagnetic resonance imaging

Confirmation that seizures arise from a visible lesion(using video telemetry)

Over 20% of seizures arising from the contralateraltemporal lobe in temporal lobe seizures

Intelligence quotient > 70 points No significant psychiatry morbidity

No medical contraindications

Age < 45 years


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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


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Ten commandments in the

pharmaco log ical treatment o f epi lepsy

Choose the correct drug for the seizuretype or epilepsy syndrome

Start at low dosage and increaseincrementally

Titrate slowly to allow tolerance to centralnervous 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 readilyobtained (if possible)


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Counsel the patient early regarding theimplications of the diagnosis and theprophylactic nature of drug therapy

Try two reasonable mono-therapy optionsbefore adding a second drug

When seizures persist, combine the besttolerated first-line drug with one of thenewer agents depending on seizure typeand mechanism of action

Simplify dose schedules and drugregimens as much as possible in patientsreceiving poly-pharmacy

Aim for the best seizure controlconsistent with the optimal quality of lifein patients with refractory epilepsy

D h i i l d i d i l i


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Drug choice in new ly diagnosed epi lepsy in

ado lescents 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


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Choice of ant iepi lept ic d rugs in ch i ldren

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

TopiramateAbsence 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


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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 increaseWrong patient

Poor compliance with medication

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


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When to stop medication

After 2-3 years period of seizures free,

must be tapering off in six month.

Normal EEG.


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Prognosis

Dependent with underlying syndrome and / orits cause

Patients compliance Reciprocal illness or medications

60-70% controlled by first-line drug ofepilepsy

10% of the rest controlled by new drugs The rest :

surgery

Institution


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Special Problems of Epilepsy

Behavioral and cognitive problem :-Label of epilepsy racial disadvantage

-Depends on location, medication, type ofseizure

-Attitudes of helpers and helped

Education :

-Discussion between doctors, families,schools teachers and the patient, stepswhich might be taken to promote normaleducation and personal development


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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


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No permitting to drive if :

Have suffered of epileptic attack at the age beforeadolescent

Medical condition caused driving a source of danger tothem 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


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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

TONIC CLONIC STATUS


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TONIC CLONIC STATUSEPILEPTICUS

Prolonged or recurrent tonic-clonic seizures

persist for 30 minutes or more. Incidence: 18 28 /100000 persons.

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,

b l h l


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Cerebral Changes in Status Epilepticus


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Status Epilepticus Phase I

Status Epilepticus Phase II


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Status Epilepticus Phase II

Status Epilepticus


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Status Epilepticus

Treatment


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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 motoractivity continuous .

Sometimes a progressive changes in the EEG.

PHYSIOLOGIC CHANGES IN


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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.


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Phase II: Phase of decompensation:

Compensatory physiological mechanisms begin to fail asseizures activity continues.

Cerebral autoregulation breaksdown progressively, seizures relatedautonomic and cardiorespiratory changes develophypotention,hypoxia and cardiac dysrithmia.

Rise intracranial pressure and systemic hypotention result cerebraloedema.

Metabolic and endocrine disturbances:acidocis.hypoglycaemia,hyponatremia and hypokalemia,acuttubular necrosis,renal failure, DIC,

Persistent convulsive movement can presipitate rhabdomyolysis.

THE MANAGEMENT OF TONIC


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THE MANAGEMENT OF TONIC-

CLONIC 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.


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DRUG TREATMENT

Premonitory stage:

Diazepam 10 mg i.v.or rectally,if status

continues,repeated after 15 minutes orLorazepam 4 mg bolus,If seizures continues>

Stages of early status:

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

Stages of established status


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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,whenseizures have been controlled for 12h,slowly tappered over 12h,or

Thiopental:100 250 mg iv bolus over 20 s ,with further 50mg boluses every 2 3 minutes until seizure arecontrolled,followed by a continues iv infusion 3 5 mg/kg/hto maintain a burst suppression pattern on the EEG.Should beslowly withdrawn 12 h after the last zeisure.


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EPILEPSY PARTIALIS CONTINUA: Spontaneous regular or irregular clonic muscle jerk,

confined to one part of the body and continuing forhours, days or weeks, there are many potential causes.

COMPLEX PARTIAL S E :

Prolonged epileptic episode, fluctuating or frequentlyrecurring 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 secondarygeneralized epilepsy of the Lennox Gestaut type.


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Epilepsy Lecture 2007.Revisi