Epilepsies

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Chapter: Essential pharmacology : Antiepileptic Drugs

These are a group of disorders of the CNS characterized by paroxysmal cerebral dysrhythmia, manifesting as brief episodes (seizures) of loss or disturbance of consciousness, with or without characteristic body movements (convulsions), sensory or psychiatric phenomena.


EPILEPSIES 

 

These are a group of disorders of the CNS characterized by paroxysmal cerebral dysrhythmia, manifesting as brief episodes (seizures) of loss or disturbance of consciousness, with or without characteristic body movements (convulsions), sensory or psychiatric phenomena. Epilepsy has a focal origin in the brain, manifestations depend on the site of the focus, regions into which the discharges spread and postictal depression of these regions. Recognised from the dawn of history as ‘disease of lightening’, it was correctly described by JH Jackson little over a century ago. Epilepsies have been classified variously; major types are described below.

 

 

I. Generalised Seizures

 

1. Generalised Tonic-clonic Seizures (GTCS, major epilepsy, grand mal): commonest, lasts 1–2 min.

 

The usual sequence is aura—cry—unconsciousness— tonic spasm of all body muscles—clonic jerking followed by prolonged sleep and depression of all CNS functions.

 

2. Absence Seizures (minor epilepsy, petit mal): prevalent in children, lasts about 1/2 min. Momentary loss of consciousness, patient apparently freezes and stares in one direction, no muscular component or little bilateral jerking. EEG shows characteristic 3 cycles per second spike and wave pattern.

 

3. Atonic Seizures (Akinetic epilepsy): Unconsciousness with relaxation of all muscles due to excessive inhibitory discharges. Patient may fall.

 

4. Myoclonic Seizures Shocklike momentary contraction of muscles of a limb or the whole body.

 

5. Infantile Spasms (Hypsarrhythmia) Seen in infants. Probably not a form of epilepsy. Intermittent muscle spasm and progressive mental deterioration. Diffuse changes in the interseizure EEG are noted.

 

II. Partial  Seizures

 

1. Simple Partial Seizures (SPS, cortical focal epilepsy): lasts 1/2–1 min. Often secondary. Convulsions are confined to a group of muscles or localized sensory disturbance depending on the area of cortex involved in the seizure, without loss of consciousness.

 

2. Complex Partial Seizures (CPS, temporal lobe epilepsy, psychomotor): attacks of bizarre and confused behaviour and purposeless movements, emotional changes lasting 1–2 min along with impairment of consciousness. An aura often precedes. The seizure focus is located in the temporal lobe.

 

3. Simple Partial Or Complex Partial Seizures Secondarily Generalized The partial seizure occurs first and evolves into generalized tonic-clonic seizures with loss of consciousness.

 

Most of the cases are primary (idiopathic), some may be secondary to trauma/surgery on head, intracranial tumour, tuberculoma, cysticercosis, cerebral ischaemia, etc. Treatment is symptomatic and the same whether epilepsy is primary or secondary.

 

Experimental Models

 

These models for testing antiepileptic drugs have also shed light on the etiopathogenesis of epilepsy.

 

1. Maximal Electroshock Seizures Brief high intensity shock is applied to the head of a rodent (just as in ECT): produces tonic flexion—tonic extension—clonic convulsions. The tonic phase (especially extensor) is selectively abolished by drugs effective in GTCS. Activity in this model represents action on spread of seizure discharge.

 

2. Pentylenetetrazol (PTZ) clonic seizures Injection of PTZ in rats or mice produces clonic convulsions which are prevented by drugs effective in absence seizures. Activity in this model represents action on seizure focus itself.

 

3. Chronic focal seizures Produced by application of alumina cream on the motor cortex of monkey.

 

4. Kindled seizures Brief bursts of weak electrical impulses are applied to the brain (especially amygdala) intermittently over days. After discharges increase progressively and tonic-clonic seizures are produced after 10–15 shocks; with time spontaneous seizures set in, usually after >100 shocks. This indicates that seizures have a self-perpetuating and reinforcing effect: more neuronal circuits are facilitated and recruited in the seizure process. Kindling is probably involved in the genesis of clinical epilepsy.

 

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