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Epilepsydr.Sasmoyohati SpS(K)
DefinitionDefinition
A A chronicchronic neurologic disorder manifesting by neurologic disorder manifesting by repeatedrepeated epileptic seizures (attacks or fits) which epileptic seizures (attacks or fits) which result from paroxysmal uncontrolled discharges of result from paroxysmal uncontrolled discharges of neurons within the central nervous system (grey neurons within the central nervous system (grey matter disease).matter disease).
The clinical manifestations range from a major motor The clinical manifestations range from a major motor convulsion to a brief period of lack of awareness. The convulsion to a brief period of lack of awareness. The stereotyped and uncontrollable nature of the attacks is stereotyped and uncontrollable nature of the attacks is characteristic of epilepsy.characteristic of epilepsy.
Pathogenesis The 19th century neurologist Hughlings
Jackson suggested “a sudden excessive disorderly discharge of cerebral neurons“ as the causation of epileptic seizures.
Recent studies in animal models of focal epilepsy suggest a central role for the excitatory neurotransmiter glutamate (increased in epi) and inhibitory gamma amino butyric acid (GABA) (decreased)
Definition of epilepsy by cause Idiopathic – no structural cause, probably
genetic
Symptomatic – structural cause e.g : drugs , BT , alcohol , CVA , infection
Cryptogenic – no structural cause found but one suspected
Epidemiology and course Epilepsy usually presents in childhood or
adolescence but may occur for the first time at any age.
Epidemiology and course 5% of the population suffer a single sz at
some time 0.5-1% of the population have recurrent sz
= EPILEPSY 70% = well controlled with drugs
(prolonged remissions); 30% epilepsy at least partially resistant to drug treatments = INTRACTABLE EPILEPSY.
Epilepsyis a symptom of numerous disorders, but in the majority
ofsufferers the cause remains unclear despite careful
historytaking,examination and investigation!
Epilepsy - Classification The modern classification of the
epilepsies is based upon the nature of the seizures rather than the presence or absence of an underlying cause.
Seizures which begin focally from a single location within one hemisphere are thus distinguished from those of a generalised nature which probably commence in a deeper structures (brainstem? thalami) and project to both hemispheres simultaneously.
Epilepsy - Classification Focal seizures – account for
80% of adult epilepsies- Simple partial seizures- Complex partial seizures- Partial seizures secondarilly
generalised
Generalised seizures
Unclassified seizures
Focal (partial) seizures Simple partial seizures Motor, sensory, vegetative or psychic
symptomatology Typically consciousness is preserved
Focal (partial) seizures Simple partial seizures Motor, sensory, vegetative or psychic
symptomatology Typically consciousness is preserved
Focal (partial) seizures Simple partial seizures Motor, sensory, vegetative or psychic
symptomatology Typically consciousness is preserved
Focal (partial) seizures Complex partial seizures (= psychomotor seizures) Initial subjective feeling (aura), loss of
consciousness, abnormal behavior (perioral and hand automatisms)
Usually originates in TL
Focal (partial) seizures Partial seizures evolving to tonic/clonic
convulsions – secondary generalised tonic/clonic seizures (sGTCS)
Generalized seizures(convulsive or non-convulsive)
Absences Myoclonic seizures Clonic seizures Tonic seizures Atonic seizures
Generalized seizures
Absences Myoclonic seizures Clonic seizures Tonic seizures Atonic seizures
Revised ILAE (International League Against Epilepsy) Seizure Classification
I. PARTIAL (FOCAL, LOCAL) SEIZURES
A. Simple partial seizuresB. Complex partial seizureC. Partial seizures evolving to generalized
tonic-clonic convulsions (GTC)
II. GENERALIZED SEIZURESA. 1. Absence seizures
2. Atypical absenceB. Myoclonic seizures, Myoclonic jerks
(simple or multiple)C. Clonic seizuresD. Tonic seizuresE. Tonic-clonic seizuresF. Atonic seizures (astatic)
III. UNCLASSIFIED EPILEPTIC SEIZURES
Includes all seizures that cannot be classified because of inadequate or incomplete data and some that defy classification in hitherto described categories. This includes some neonatal seizures, e.g., rhythmic eye movements, chewing, and swimming movements.
Some Possible Triggers
Missed medication Lack of sleep Stress / boredom Irregular eating Over indulgence of alcohol Hormones Visual triggers (very rare)
Epilepsy – Investigation The concern of the clinician is that epilepsy may be
symptomatic of a treatable cerebral lesion. Routine investigation: Haematology, biochemistry
(electrolytes, urea and calcium), chest X-ray, electroencephalogram (EEG).Neuroimaging (CT/MRI) should be performed in all persons aged 25 or more presenting with first seizure and in those pts. with focal epilepsy irrespective of age.
Specialised neurophysiological investigations: Sleep deprived EEG, video-EEG monitoring.
Advanced investigations (in pts. with intractable focal epilepsy where surgery is considered): Neuropsychology, Semiinvasive or invasive EEG recordings, MR Spectroscopy, Positron emission tomography (PET) and ictal Single photon emission computed tomography (SPECT)
Epilepsy Differential DiagnosisThe following should be considered in the diff. dg. of epilepsy: Syncope attacks (when pt. is standing; results from global
reduction of cerebral blood flow; prodromal pallor, nausea, sweating; jerks!)
Cardiac arrythmias (e.g. Adams-Stokes attacks). Prolonged arrest of cardiac rate will progressively lead to loss of consciousness – jerks!
Migraine (the slow evolution of focal hemisensory or hemimotor symptomas in complicated migraine contrasts with more rapid “spread“ of such manifestation in SPS. Basilar migraine may lead to loss of consciousness!
Hypoglycemia – seizures or intermittent behavioral disturbances may occur.
Narcolepsy – inappropriate sudden sleep episodes Panic attacks PSEUDOSEIZURES – psychosomatic and personality disorders
Epilepsy - Treatment The majority of pts respond to drug therapy
(anticonvulsants). In intractable cases surgery may be necessary. The treatment target is seizure-freedom and improvement in quality of life!
Basic rules for drug treatment: Drug treatment should be simple, preferably using one anticonvulsant (monotherapy). “Start low, increase slow“. Polytherapy is to be avoided especially as drug interactions occur between major anticonvulsants.
The commonest drugs used in clinical practice are: Carbamazepine, Sodium valproate, Phenytoin (first line drugs) Lamotrigine, Topiramate, Levetiracetam, Pregabaline (new AEDs)
Epilepsy – Treatment (cont.) If pt is seizure-free for three years, withdrawal of
pharmacotherapy should be considered. Withdrawal should be carried out only if pt is satisfied that a further attack would not ruin employment etc. (e.g. driving licence). It should be performed very carefully and slowly! 20% of pts will suffer a further sz within 2 yrs.
The risk of teratogenicity is well known (~5%), especially with valproates, but withdrawing drug therapy in pregnancy is more risky than continuation. Epileptic females must be aware of this problem and thorough family planning should be recommended. Over 90% of pregnant women with epilepsy will deliver a normal child.
Treatment Goals No seizures No side effects Monotherapy Once daily dosing No blood tests
What actually happens 70% seizure free with one drug
With careful monitoring and adjustment
5% to 10% seizure free with two or more drugs
20% still have seizures
Principals of pharmacological treatment 1 Use the right drug for the seizure type Use one drug and increase the dose until a
therapeutic effect is gained or toxicity appears (maximum tolerated dose)
Monitor treatment including blood levels If required add a second drug.
If a response consider slowly removing the first drug
Principals of pharmacological treatment 2 If monotherapy fails use two drugs
Review and replace the combinations used Add in a third drug if necessary Be prepared to accept that a significant
reduction in seizure frequency maybe as good as it gets
Modes of action1 Suppress action potential Sodium channel blocker or modulator Potassium channel opener2 Enhance GABA transmission GABA uptake inhibitor GABA mimetics3 Suppression of excitatory transmission
Choice of antiepileptic 1Seizure type Drug of choice Alternatives
Partial simple &Partial complex
CarbamazepinePhenytoinValproate
LamotrigineGabapentinLevetiracetamTopiramateTiagabineOxcarbazepinePhenobarbital
Choice of antiepileptic 2Seizure type Drug of choice Alternatives
Generalised tonic clonic
CarbamazepinePhenytoinValproate
LamotrigineTopiramatePhenobarbital
Absence EthosuximideValproate
LamotrigineClonazepam
Atypical absenceAtonic, myoclonic
Valproate Clonazepam
Drugs to be used with care Aminophylline Amphetamines Analgesics Antibiotics Antidepressants Antimuscarinics Antipsychotics Baclofen Bupropion Donepezil etc
Cyclosporin Cocaine Isoniazid Lignocaine Mefloquine NSAIDs Opioids Oral contraceptives Vincristine
Epilepsy – Surgical Treatment A proportion of the pts with intractable epilepsy
will benefit from surgery. Epilepsy surgery procedures: Curative (removal of
epileptic focus) and palliative (seizure-related risk decrease and improvement of the QOL)
Curative (resective) procedures: Anteromesial temporal resection, selective amygdalohippocampectomy, extensive lesionectomy, cortical resection, hemispherectomy.
Palliative procedures: Corpus callosotomy and Vagal nerve stimulation (VNS).
Status Epilepticus
A condition when consciousness does not return between seizures for more than 30 min. This state may be life-threatening with the development of pyrexia, deepening coma and circullatory collapse. Death occurs in 5-10%.
Status epilepticus may occur with frontal lobe lesions (incl. strokes), following head injury, on reducing drug therapy, with alcohol withdrawal, drug intoxication, metabolic disturbances or pregnancy.
Treatment: AEDs intravenously ASAP, event. general anesthesia with propofol or thipentone should be commenced immediately.