The time course of acquired epilepsy: Implications for therapeutic intervention to suppress epileptogenesis

Abstract

Relatively little is known about the time course of the development of spontaneous recurrent seizures (i.e., epileptogenesis) after brain injury in human patients, or even in animal models. This time course is determined, at least in part, by the underlying molecular and cellular mechanisms responsible for acquired epilepsy. An understanding of the critical mechanistic features of acquired epilepsy will be useful, if not essential, for developing strategies to block or suppress epileptogenesis. Here, data on the time course of the development of spontaneous recurrent seizures are summarized from experiments using nearly continuous electrographic (EEG) recordings in (1) kainate-treated rats, which are a model of temporal lobe epilepsy, and (2) rats subjected to unilateral carotid occlusion with superimposed hypoxia at postnatal day 7, which is a model of perinatal stroke. Although the classical view of the development of epileptogenesis is a step-function of time after the brain injury, with a latent period present between the brain injury and the first unprovoked seizure, the data described here show that seizure frequency was a sigmoid function of time after the insult in both animal models. Furthermore, the spontaneous recurrent seizures often occurred in clusters, even shortly after the first spontaneous seizure. These data suggest that (1) epileptogenesis is a continuous process that extends past the first spontaneous clinical seizure, (2) seizure clusters can obscure this continuous process, and (3) the potential time for administration of a therapy to suppress acquired epilepsy extends well past the first clinical seizure.