epilepsy lecture 2007.revisi
TRANSCRIPT
-
7/29/2019 Epilepsy Lecture 2007.Revisi
1/62
EPILEPSY
Yustiani Dikot
-
7/29/2019 Epilepsy Lecture 2007.Revisi
2/62
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
-
7/29/2019 Epilepsy Lecture 2007.Revisi
3/62
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
-
7/29/2019 Epilepsy Lecture 2007.Revisi
4/62
FOCAL EPILEPTOGENESIS Asynchronous burst firing in some
hypocampal and cortical neurons
-
7/29/2019 Epilepsy Lecture 2007.Revisi
5/62
Generalized epileptogenesis :
asynchronous burst firing in abnormal
thalamocortical interaction
-
7/29/2019 Epilepsy Lecture 2007.Revisi
6/62
EPIDEMIOLOGY
Developed countries :
annual incidence 50-70 cases per
100.000
Developing countries : prevalence 1%
Incidence varies with age
-
7/29/2019 Epilepsy Lecture 2007.Revisi
7/62
Incidence of epilepsy in relation to age
-
7/29/2019 Epilepsy Lecture 2007.Revisi
8/62
ETIOLOGY
Idiopathic
Cryptogenic
Symptomatic
-
7/29/2019 Epilepsy Lecture 2007.Revisi
9/62
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
-
7/29/2019 Epilepsy Lecture 2007.Revisi
10/62
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
-
7/29/2019 Epilepsy Lecture 2007.Revisi
11/62
Congenital (inherited or acquired)
Cortical dysplasia/dysgenesis
Cerebral tumours
Vascular malformations
Prenatal injury
-
7/29/2019 Epilepsy Lecture 2007.Revisi
12/62
Epilepsy alone:
Benign familial neonatal convulsionBenign familial infantile convulsion
Juvenile myoclonic epilepsy
Familial frontal lobe epilepsyIdiopathic generalize epilepsy
-
7/29/2019 Epilepsy Lecture 2007.Revisi
13/62
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.
-
7/29/2019 Epilepsy Lecture 2007.Revisi
14/62
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)
-
7/29/2019 Epilepsy Lecture 2007.Revisi
15/62
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
-
7/29/2019 Epilepsy Lecture 2007.Revisi
16/62
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
-
7/29/2019 Epilepsy Lecture 2007.Revisi
17/62
Generalized seizures (convulsive or non-convulsive)
Absence seizures Typical
Atypical
Myoclonic seizures
Clonic seizures
Tonic seizures
Tonic clonic seizures
Atonic seizures Unclassified seizures
-
7/29/2019 Epilepsy Lecture 2007.Revisi
18/62
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
-
7/29/2019 Epilepsy Lecture 2007.Revisi
19/62
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
-
7/29/2019 Epilepsy Lecture 2007.Revisi
20/62
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
-
7/29/2019 Epilepsy Lecture 2007.Revisi
21/62
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)
-
7/29/2019 Epilepsy Lecture 2007.Revisi
22/62
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)
-
7/29/2019 Epilepsy Lecture 2007.Revisi
23/62
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
-
7/29/2019 Epilepsy Lecture 2007.Revisi
24/62
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
-
7/29/2019 Epilepsy Lecture 2007.Revisi
25/62
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
-
7/29/2019 Epilepsy Lecture 2007.Revisi
26/62
EEG
-
7/29/2019 Epilepsy Lecture 2007.Revisi
27/62
EEG
-
7/29/2019 Epilepsy Lecture 2007.Revisi
28/62
BRAIN IMAGING
Essential, particularly in partial onset
seizures
Computerized tomography (CT)
Magnetic resonance imaging (MRI)
Structural lesion
-
7/29/2019 Epilepsy Lecture 2007.Revisi
29/62
MRI
-
7/29/2019 Epilepsy Lecture 2007.Revisi
30/62
MRI
-
7/29/2019 Epilepsy Lecture 2007.Revisi
31/62
MRI
-
7/29/2019 Epilepsy Lecture 2007.Revisi
32/62
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
-
7/29/2019 Epilepsy Lecture 2007.Revisi
33/62
Single Photon Emission CT (SPECT)
Positron Emission Tomography (PET)
MRI spectroscopy
Functional MRI
Functional cerebral changes
Useful adjuncts in candidate epilepticsurgery
-
7/29/2019 Epilepsy Lecture 2007.Revisi
34/62
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
-
7/29/2019 Epilepsy Lecture 2007.Revisi
35/62
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
-
7/29/2019 Epilepsy Lecture 2007.Revisi
36/62
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
-
7/29/2019 Epilepsy Lecture 2007.Revisi
37/62
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
-
7/29/2019 Epilepsy Lecture 2007.Revisi
38/62
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)
-
7/29/2019 Epilepsy Lecture 2007.Revisi
39/62
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
-
7/29/2019 Epilepsy Lecture 2007.Revisi
40/62
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
-
7/29/2019 Epilepsy Lecture 2007.Revisi
41/62
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
-
7/29/2019 Epilepsy Lecture 2007.Revisi
42/62
-
7/29/2019 Epilepsy Lecture 2007.Revisi
43/62
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)
-
7/29/2019 Epilepsy Lecture 2007.Revisi
44/62
When to stop medication
After 2-3 years period of seizures free,
must be tapering off in six month.
Normal EEG.
-
7/29/2019 Epilepsy Lecture 2007.Revisi
45/62
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
-
7/29/2019 Epilepsy Lecture 2007.Revisi
46/62
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
-
7/29/2019 Epilepsy Lecture 2007.Revisi
47/62
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
-
7/29/2019 Epilepsy Lecture 2007.Revisi
48/62
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
-
7/29/2019 Epilepsy Lecture 2007.Revisi
49/62
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
-
7/29/2019 Epilepsy Lecture 2007.Revisi
50/62
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
-
7/29/2019 Epilepsy Lecture 2007.Revisi
51/62
Cerebral Changes in Status Epilepticus
-
7/29/2019 Epilepsy Lecture 2007.Revisi
52/62
Status Epilepticus Phase I
Status Epilepticus Phase II
-
7/29/2019 Epilepsy Lecture 2007.Revisi
53/62
Status Epilepticus Phase II
Status Epilepticus
-
7/29/2019 Epilepsy Lecture 2007.Revisi
54/62
Status Epilepticus
Treatment
-
7/29/2019 Epilepsy Lecture 2007.Revisi
55/62
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
-
7/29/2019 Epilepsy Lecture 2007.Revisi
56/62
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.
-
7/29/2019 Epilepsy Lecture 2007.Revisi
57/62
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
-
7/29/2019 Epilepsy Lecture 2007.Revisi
58/62
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.
-
7/29/2019 Epilepsy Lecture 2007.Revisi
59/62
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
-
7/29/2019 Epilepsy Lecture 2007.Revisi
60/62
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.
-
7/29/2019 Epilepsy Lecture 2007.Revisi
61/62
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.
-
7/29/2019 Epilepsy Lecture 2007.Revisi
62/62