Seizure probability in animal models of acquired epilepsy: a perspective on the concept of the preictal state

The concept of a preictal state is based on the belief that it may be possible to predict seizures before they occur. The preictal state is viewed as a time period when a seizure is practically inevitable, or at least a period of greatly increased seizure probability. Changes in seizure frequency may provide insight into how seizure probability increases after brain injury. Here, time-dependent changes in the frequency of spontaneous recurrent seizures after brain injury are summarized from published, nearly continuous, electrographic (EEG) recordings of kainate-treated rats and neonatal rats subjected to hypoxia-ischemia. For these animal models, seizure frequency - and thus seizure probability - was a sigmoid function of time after the brain injury. This observation differs from the traditional view, where the development of epilepsy after brain injury is a step-function of time, and the latent period is the time between a brain injury and the first spontaneous seizure. Based on backward extrapolation of the plots of seizure frequency versus time, these data suggest that seizure probability increases continuously during the latent period. Also, spontaneous recurrent seizures frequently occurred in clusters, suggesting that the intra-cluster seizure intervals are periods of high seizure probability. Thus, seizure probability progressively increases as a function of time after an epileptogenic brain injury, and is particularly high between seizures within a cluster, as compared to the time between clusters. These data suggest that the detectors of the preictal state need to be accurate (and tested) over a very wide range of seizure probabilities, and that studies on the physiological events that occur during seizure clusters may provide insight on the properties of the preictal state.