This study is designed to examine the events leading up to behavioral seizures, the subsequent development of the mature epileptic state and the possible effects standard anticonvulsants may have on this evolution using a newly developed animal model of partial seizures. Partial epilepsy represents the most common chronic seizure disorder which is refractory to standard therapy, but little is known about the mechanisms leading up to spontaneous seizures or about the natural history of the disease once it is established. In the course of this project the following topics will be examined. 1)The events preceding the first behaviorally apparent seizure are unknown. It has been hypothesized that the first overt manifestations are preceded by a number of subclinical electrographic seizures which intensify in a kindling like process. This question will be examined by determining whether a number of electrographic seizures occur before the first motor seizure. 2) One theory has long held that there is a tendency for seizures to worsen over time, although remissions have also been achieved. The second experiment will follow the natural history of this seizure model to determine whether seizure frequency increases with succeeding seizures. 3) Prophylactic or early treatment has been advocated as a means of lessening the severity of the disease, but its use is controversial. This experiment will determine the role of anticonvulsant therapy in changing the natural history of the seizures established in the first 2 experiments. These experiments will examine these critical questions in the ontogeny of partial seizures using the new long term monitoring technology, providing new insights into the mechanisms leading to the chronic epileptic state.
