Chapter 23 Involvement of glutamate in human epileptic activities

Abstract

Publisher Summary Epilepsy may be described as a disruption of the normal balance between excitation and inhibition. Much effort has been devoted toward understanding the role of perturbations of the excitatory neurotransmitter glutamate. Glutamatergic abnormalities are well established for certain human epilepsies. In the past, elevated brain glutamate was found in the brain of a child who died because of the status epilepticus related to pyridoxine dependency; a genetic condition in which glutamic acid decarboxylase (GAD)—the enzyme that converts glutamate to gamma-aminobutyric acid (GABA)—does not function normally. In this patient, the effect of dysfunctional GAD could not be isolated from the effects of status epilepticus. Several antiepileptic drugs have anti-glutamatergic actions that may account for a part of their antiepileptic effects. Felbamate inhibits binding of glycine at the NMDA receptor. Lamotrigine and perhaps carbamazepine may decrease presynaptic glutamate release by blocking sodium and perhaps calcium channels. The concept of epilepsy as an excess of excitatory activity has made glutamate an appealing target for study. Most evidence of its involvement is indirect, as elevated glutamate levels in brain or cerebrospinal fluid (CSF) of individuals with frequent seizures could be a result of metabolic, rather than neurotransmitter, glutamate.