Epilepsy is a chronic neurological disorder that is manifested in the form of recurrent, spontaneous seizure episodes or convulsions, the latter reflecting sudden, stereotyped episodes with accompanying changes in motor activity, sensation, and behavior.1'2 Convulsions can also be accompanied by muscle spasms and a loss of consciousness depending on the type of epilepsy. These are thought to result from an imbalance, occurring in discrete anatomical pathways in the brain, between the major excitatory and inhibitory systems, glutamate and g-amino-buytric acid (GABA), which leads to abnormal electrical discharges. Convulsions induce alterations in neurons, glia, and neuronal circuits that include alterations in membrane receptors and neurotransmitter uptake sites, both neurogenesis and apoptosis, astrocyte proliferation, and axonal sprouting. These phenomena increase the susceptibility to additional convulsive episodes and cognitive dysfunction.

Drugs to treat epilepsy (Table 1), antiepileptic drugs (AEDs) protect against seizures via actions at a diversity of targets, primarily ion channels.3,4 In most instances, AEDs represent chronic therapy for individuals with epilepsy.

Epilepsy is the most common neurological disorder in humans, affecting 1-2% of the global population. According to World Health Organization data, approximately 50 million people worldwide, a prevalence of 50 per 100000 of the general population, suffer from epilepsy. In the USA approximately 180000 new cases of epilepsy are reported each year with 2.5 million patients having experienced active epileptic episodes within the past 5 years.5 Between 0.8% and 1.2% of children and between 0.3% and 0.7% of adults experience recurrent seizures with 3% of the population having at least one seizure during their life. For the majority of people, lifelong treatment is necessary in the form of medications although vagal nerve stimulation6 and surgery at defined resectable seizure foci7-9 are also options to treat epilepsy. Approximately 30-40% of patients with epilepsy fail to achieve freedom from seizures, even with current

Table 1 Postulated mechanisms of action of anticonvulsant drugs4


Voltage-sensitive blockade

ion channel

GABAa receptor modulator

Increased GABA levels

Kainate/AMPA receptor blockade

Carbonic anhydrase inhibition

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