Abstracts

One of the hallmarks of acquired epilepsy is the presence of a latent period between the initial brain injury and the onset of chronic recurrent seizures. During this quiescent period, numerous molecular and cellular alterations are thought to underlie epileptogenesis. We hypothesized that the duration of the latent period (i.e., the time to the first chronic seizure) would be inversely related to the rate of seizure progression (i.e., the increase in seizure frequency over time). In order to asses this hypothesis, we used nearly continuous electroencephalographic (EEG) recordings (1824 h out of 2400 h, 76%) through bilateral intra-hippocampal electrodes via radiotelemetry for 100 days after kainate-induced status epilepticus (i.e., the repeated low-dose kainate model). Electrographic seizure frequency was a logistic function of time after status epilepticus: a low and variable seizure rate led to an exponential increase in EEG seizure frequency with a final plateau phase and stabilization of the EEG seizure rate. The measured latent period (mean = 13.2 [underline]+[/underline] 4.78 days, n = 6) did not correlate with measures of EEG seizure progression (e.g., time to reach 50% on a sigmoid curve; r² = 0.63, p=0.20). Even with epochs of failed recording, we estimate that the measured latent periods could only be in error by 1 day, and the ability to collect data from 76% of the 100-day study duration provided a relatively accurate measure of seizure progression. In contrast to the observed changes in seizure frequency, mean EEG seizure duration remained constant at about 40-50 sec over the 100-day time period. An increase in clusters of seizures (e.g., the number of EEG seizures occurring within 60 min of each other) marked the exponential growth phase of EEG seizure progression. These studies emphasize that measurement of the actual latent period is extremely difficult, which is due to the possibility of early undetected seizures and the high variability of the interseizure intervals in the early stages of epileptogenesis. The data suggest that the actual latent period in this model is approximately 2 weeks, which is shorter than previous measurements (e.g., based on intermittent behavioral monitoring) of the latent period in this model. The lack of a detectable relationship between the apparent latent period and measures of seizure progression suggests that the latent period may not be the best measure of the temporal aspects of epileptogenesis, and that the molecular and cellular mechanisms underlying epileptogenesis probably continue to occur throughout the slow rising and exponential phases of seizure progression. (Supported by National Institutes of Health (NS 045144).)