Functional Anatomy of Spontaneous Seizures in a Rat Model of Limbic Epilepsy

PURPOSE: The substrate of seizure initiation in partial epilepsy is not well understood. Although many studies imply a focus that is will localized to a single structure, some information suggests that seizures arise regionally with simultaneous or near-simultaneous onset at several separate sites. To determine the physiological pattern of seizure onset, recordings were made of spontaneous seizures from multiple limbic structures in a rat model of limbic epilepsy. METHODS: Seventeen rats with chronic spontaneous limbic seizures that occurred after an episode of electrical hippocampal stimulation-induced status epilepticus (SE) underwent chronic recording of seizures with a minimum of four electrodes placed bilaterally in the midventral hippocampus and either the amygdala or piriform cortex. As many as 15 of the first recorded spontaneous seizures (mean of 12 seizures, range 2-15) was evaluated for each animal with regard to pattern of seizure onset (focal hippocampal, focal nonhippocampal, or diffuse). The results were evaluated for number of seizure patterns displayed by each animal and the potential change in the pattern of onset with successive seizures (from the first to the fifteenth). RESULTS: In all, 210 seizures were evaluated beginning 1 week after SE and with monitoring lasting < or = 18 weeks (mean recording duration 6 weeks) to record a maximum of 15 seizures for each animal. Overall, 54% of the seizures were of diffuse onset, 25% were of nonhippocampal onset, and 21% were of hippocampal onset. Eight of the 17 (47%) animals had seizures with all three patterns of onset. Evaluation of the evolution of the pattern of onset from the first to the fifteenth seizure recorded for the animals showed a clear tendency for the later seizures to have diffuse onsets (regression analysis r = 0.737, p < 0.002). Qualitative histologic analysis demonstrated neuronal loss in the recorded regions. CONCLUSIONS: These findings indicate that the epileptogenic zone is broad in this model of limbic "focal" epilepsy and suggest that the substrate for seizure generation is distributed over several structures.