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
HypoxiaHypoglycaemiaHypocalcaemia
FebrileSeizures
IntracranialInfections
Birth traumaIntracranial
haemorrhage
Congenital anomaliesTuberous sclerosisStorage diseases
1 5 100 20
Head Injuries
Drugs and
alcohol
Genetic epilepsies Cerebral tumours
60
Cerebrovascular degenerations
Age (years)
Factors lowering seizure thresholdCommon 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 generalizedGeneralized 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 relatedAuraSpecific 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 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 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