Abstracts

Rationale: Mesial Temporal Lobe Epilepsy (MTLE) is the most frequent form of epilepsy (2.5 million Americans). Only 11-25% of MTLE patients become seizure free with Anti-Epileptic medication. Surgery is effective for about 75% of selected patient population. Electrical stimulation of the hippocampal structures has shown promising therapeutic effects. However, the optimum target of the stimulation is unclear. Stimulation of a fiber tract that can activate a large portion the hippocampus should suppress seizures and/or prevent their propagation. The ventral hippocampal commissure (VHC) innervates major portions (left and right) of the hippocampus in rats. The purpose of this study was to test the hypothesis that seizure activity in-vivo in chronic rat preparation could be suppressed by applying electrical stimulation to the VHC from a single electrode location. Methods: A chronic kindling animal model of temporal lobe epilepsy model was developed in Sprague Dawley rats. The model produces spontaneous seizures following 20 minutes of stimulation of the lateral nucleus of the amygdala. Two depth electrodes were implanted in both CA3 pyramidal neurons in hippocampus to record epileptiform activity, one electrode was implanted at the ventral hippocampal commissure for application of low frequency stimulation and one electrode was implanted at left amygdalae to induce the seizure. Following a three month period of epileptogenesis, baseline seizure frequency was determined by continuous video and electrographic monitoring of the bilateral hippocampi for 2 weeks. Low Frequency Stimulation (LFS) (1 Hz) was then applied continuously for 60 minutes ON and 15 minutes OFF, for two weeks, and mean seizure frequency before, during and after treatment were compared. Results: Mean seizure frequency analysis was carried out for eight animals. The mean number of seizures per day was calculated before, during, and after treatment for each rat. Mean seizure frequency was 3 (2.97 ± 2.87) seizures per day before treatment, <1(0.418 ± 0.388) seizure per day during treatment, and about 1(1.22 ± 1.23) seizure per day after stimulation had ceased. The mean decrease in seizure frequency was 84 %( 80.3 ± 13.2 %). A statistically significant difference (p <0.05) was observed between the “Baseline” and “Stimulation” states, as well as a noticeable, but not statistically significant (p = 0.0544), difference between the “Stimulation” and “After” states indicating that the seizures frequency did not return to its baseline level. Conclusions: This study shows that LFS stimulation of the VHC is effective for suppressing seizures in a rat model of temporal lobe epilepsy. Current studies are under way to determine whether LFS will be effective for patients with epilepsy using the dorsal hippocampal commissure (DHC) as a stimulation target. Preliminary data with cortical evoked potentials from depth electrodes show that the DHC is a functional pathway of hippocampus and connected with mesial temporal structures bilaterally in human. Funding for this work was provided by the Coulter-Case Translational Research Partnership.