Abstracts

Rationale: Recent evidence in animals and humans suggests that low-frequency stimulation (LFS) has significant antiseizure properties. The central piriform cortex (cPC) has been demonstrated to be a highly susceptible seizure-trigger zone, and may be critical for the initiation and propagation of seizures originating from cortical and limbic foci. We studied the effect of LFS of the cPC on seizure frequency and severity in the kainate seizure model in rats.Methods: Adult Sprague-Dawley rats (n=6; Hilltop Lab Animals Inc, Scottdale, PA) were implanted with tripolar electrodes in the left cPC and recording electrodes bilaterally in the hippocampal CA3 regions. Rats were monitored continuously with video-EEG (Triangle Biosystems International, Durham, NC) for the emergence of spontaneous recurrent seizures after induction of status epilepticus by intraperitoneal kainic acid injections (KA; Milestone PharmTech USA Inc, New Brunswick, NJ). After two weeks of baseline recordings to determine seizure frequency, LFS of the cPC was applied 60-min on, 15-min off, for two weeks with 1 Hz biphasic square waves, each 0.1 ms in duration, at 200 µA. Another period of 2 weeks of video-EEG monitoring was done after the cessation of LFS. Changes in seizure frequency between baseline, LFS, and post-LFS were analyzed using the Wilcoxon matched-pairs signed rank test. All seizure frequencies are represented as mean values and standard error of the mean.Results: The most severe seizure type (Stage 5 on the Racine scale) occurred at a frequency of 0.2±0.06 seizures per day during baseline, but was absent during LFS. Overall, seizure frequency significantly decreased during LFS (p = 0.047; 0.3±0.12 seizures/day) compared to baseline (0.8±0.30 seizures/day). Additionally, post-LFS seizure frequency (0.2±0.12 seizures/day) remained significantly reduced compared to the baseline (p = 0.016). There was no significant difference between seizure frequencies during LFS and post-LFS (p = 0.19).Conclusions: Electrical stimulation for treatment of epilepsy has shown limited benefit when compared to remarkable benefits in other neurologic and psychiatric disorders. While LFS has been underutilized, our findings suggest that LFS of the cPC significantly reduced the severity and frequency of seizures in a well studied animal model, and to have a lasting carry-over effect.