Interictal spikes: harbingers or causes of epilepsy?

Interictal spikes are brief paroxysmal electrographic discharges observed between spontaneous recurrent seizures in epileptic patients. The relationship between interictal spikes and the seizures that define acquired epilepsy has been debated for decades. Recent studies using long-term continuous electrographic recordings from the hippocampus and cortex in rats with kainate-induced epilepsy suggest that electrographic spikes, with waveforms similar to interictal spikes, precede the occurrence of the first spontaneous epileptic seizure. These data raise the possibility that spikes might serve as a surrogate marker of ongoing chronic epileptogenesis. Additionally, electrographic spikes might actually contribute to the development and maintenance of the epileptic state (i.e., the increased probability of spontaneous recurrent seizures). Correlational evidence for such a causal relationship has recently also been obtained in an in vitro model of epileptogenesis using organotypic hippocampal slices. Testing for a causal relationship will ultimately require selective anti-spike medications. Although no such agents currently exist, this new preparation is amenable to moderate-throughput screening, which should accelerate their discovery. Anti-spike agents may also be of benefit in ameliorating the cognitive dysfunctions associated with epilepsy, to which spike activity may contribute.