Abstracts

After CNS injuries in humans, an interval of several months or years usually occurs before the subsequent onset of spontaneous recurrent seizures (i.e., epilepsy). Thus, a [quot]latent period[quot] is generally observed between a brain injury and the onset of the spontaneous recurrent seizures that represents chronic epilepsy. Relatively little is known about the temporal progression of epileptogenesis. We hypothesized that, in an animal model of temporal lobe epilepsy, interictal spike frequency increases in proportion to seizure frequency during epileptogenesis. Eight 2-month-old Sprague Dawley rats were each implanted with a three-channel radiotelemetry system (DSI) to record electrical activity from each dentate gyrus and the neocortex. Five of these rats were treated with kainic acid until status epilepticus occurred for [gt]3 h. These rats were then monitored nearly continuously using video EEG for the next 5 months. The recordings were processed using analysis routines written in Visual Basic 6.0 to isolate and quantify interictal spikes and seizures. Interictal spikes were consistently present immediately after the kainate-induced status epilepticus, and occasional electrographic seizures could occur at any time after kainate treatment. This period of low and stable electrographic seizure frequency lasted between 2 and 23 weeks. Subsequently there was a dramatic increase in both the number of seizures and the number of interictal spikes per day in all 5 animals. This increase resulted in unambiguous inflection points in plots of seizure and interictal spike frequency versus time after kainate-induced status epilepticus. In all five cases, the inflection point for the interictal spikes either preceded or was coincident with that of the seizures. The times from kainate-induced status to the spike vs. seizure inflection points were not significantly different in the first 5 animals (paired t-test, p=0.10). After the onset of occasional spontaneous seizures following kainate-induced status epilepticus, there is a point in time when seizure frequency undergoes a substantial increase (i.e., an inflection in the plot of seizures per day versus time after kainate treatment). A relationship was detected between the appearance of an increased frequency of interictal spikes and an increase in the number of seizures per day. One of the implications of these data is that the interictal spike frequency in EEG recordings may be predictive of an increase in seizure probability, which may useful in the clinical management of human brain injury. (Supported by National Institute of Health
Epilepsy Foundation of America
American Epilepsy Society)