What are Epilepsies?

• Groupf of disorders of the CNS characterized by paroxysmal cerebral dysrhythmia, manifesting as brief episodes (seizure) of loss of consciousness, with or without characteristic body movements (convulsions), sensory or psychiatric phenomena

What are seizures?

• A seizure is a transient alteration of behaviour due to the disordered, synchronous, and rythmic firing of populations of brain neurones.

• Seizure can be non-epileptic and can be evoked in normal brain.

• A seizure is a paroxysmal behavioral spell generally caused by an excessive disorderly discharge of cortical nerve cells.

Clinical Presentation of Epilepsies

• Epilepsy is a syndrome of two or more unprovoked or recurrent seizures on more than one occasion.

• Epileptic seizures range from clinically undetectable(electrographic seizures) to convulsions

Types

1) Generalized A) Generalized tonic-clonic seizuresB) Absence seizuresC) Atonic seizure D) Myoclonic seizuresE) Infantile spasms

Types

• 2) Partial (focal) SeizuresA. Simple partial seizuresB. Complex partial seizures

Causes of Epilepsy

• Acute • Congenital

Causes of epilepsy

• Acute epilepsy– Cortical damage– Trauma– Stroke– Neoplasm– Autoimmune effects

Classification of antiepileptic drugs

• Hydantoins: Phenytoin. Phosphenytoin• Barbiturates: Phenobarbitone• Iminostilbenes: carbamazepine, oxcarbazepine• Succinimides: Ethosuximide• Aliphatic carboxylic acid: Valproic• Benzodiazepines: Clonazepam, diazepam,

lorazepam• New agents: Gabapentin, lemotrigine, tiagabine,

topiramate

Mechanisms of seizure and antiseizure drugs

• Common ones• Modification of ion conductance– Prolongation of Na+ channels inactivation– Inhibition of ‘T’ type Ca++ current

• Increase inhibitory (GABAergic) transmission• Glutamate receptor antagonism (NMDA,

AMPA, or Kainic acid)• Genetic Mechanisms

Anticonvulsant Mechanism

• The sodium Channel:• A) RESTING STATE• B) Arrival of action potential causes

depolarization and channel opens allowing sodium to flow in.

• C) Refractory State, Inactivation – reduce the rate of recovery.

Sodium channel

• Drugs acting via this channel:– Phenytoin, sodium valproate,– Carbamazepine, lamotrigine,– Topiramide and zonisamide

Anticonvulsant mechanism

• T type Ca++ current inhibition:• T type current is responsible for 3 Hz spike and

wave• Throughout the thalamus T current has large

amplitudes• Burst of action potential is by action of T current• In absence seizure• Drugs – ethosuximide, valproate and

trimethadione

Anticonvulsant mechanism

• The GABA mediated Cl channel opening• Drugs: barbiturates, benzodiazepines,• Vigabatrin, gabapentin and valproate

Phenobarbitone

• Mechanism of action