Epilepsy

dr.Sasmoyohati SpS(K)

Definition

A chronic neurologic disorder manifesting by repeated epileptic seizures (attacks or fits) which result from paroxysmal uncontrolled discharges of neurons within the central nervous system (grey matter disease). The clinical manifestations range from a major motor convulsion to a brief period of lack of awareness. The stereotyped and uncontrollable nature of the attacks is 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.

Epilepsy
is a symptom of numerous disorders, but in the majority of sufferers the cause remains unclear despite careful history taking,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 seizures B. Complex partial seizure C. Partial seizures evolving to generalized tonic-clonic convulsions (GTC)

II. GENERALIZED SEIZURES

A. 1. Absence seizures 2. Atypical absence B. Myoclonic seizures, Myoclonic jerks (simple or multiple) C. Clonic seizures D. Tonic seizures E. Tonic-clonic seizures F. 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 Diagnosis

The 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 action
1 Suppress action potential Sodium channel blocker or modulator Potassium channel opener 2 Enhance GABA transmission GABA uptake inhibitor GABA mimetics 3 Suppression of excitatory transmission

Choice of antiepileptic 1
Seizure type Drug of choice Carbamazepine Phenytoin Valproate Alternatives Lamotrigine Gabapentin Levetiracetam Topiramate Tiagabine Oxcarbazepine Phenobarbital Partial simple & Partial complex

Choice of antiepileptic 2
Seizure type Drug of choice Alternatives Lamotrigine Topiramate Phenobarbital Lamotrigine Clonazepam Clonazepam Generalised tonic Carbamazepine clonic Phenytoin Valproate Absence Ethosuximide Valproate Atypical absence Valproate Atonic, myoclonic

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.