Abstracts

Rationale: Epileptic seizures originating from primary motor cortex are often pharmacoresistant. Because of location of epileptic focus in eloquent areas, resective surgery is not a suitable treatment option. Surgical excision carries risk of permanent major functional deficits. Hence alternative therapies like DBS need to be explored for treating such seizures. It is known that basal ganglia are strongly interconnected with the motor cortex. The aim of the present paper was first to show electrophysiological clues of the involvement of BG during motor seizure and second, to assess the efficacy of DBS of Basal Ganglia in treating focal motor seizures.Methods: : We first developed a stable, predictable primate model of focal motor epilepsy by intracortical injection of penicillin and documented it s pharmacoresistance. Micro Electrode Recordings (MER) of basal ganglia were performed in two monkeys during ictal and interictal periods. These studies showed that input structures of basal ganglia such as GPe, Putamen and Subthalamic nucleus (STN) are strongly modified during seizures. Indeed the mean firing rate of neurons of the STN and Putamen increased significantly and the percentage of oscillatory neurons synchronized with the ictal EEG became higher during seizures as compared to interictal periods. Based on these findings, we targeted STN to study therapeutic effect of electrical inhibition of the structure using high frequency stimulation. Two other primates were used for this part of study. We stereotactically implanted DBS electrodes in the STN and the stimulator was embedded at the back of the animals. Subthreshold electrical stimulations at 130 Hz were applied to STN. Stimulator was turned ON when penicillin was injected. Sham stimulation at 0 volt was used as a control situation, each monkey being its own control. The time course, number and duration of seizures occurring in each epochs of 1 h were compared during ON and sham stim periods. Each experimental session lasted 6 to 8 hours. Results: : Data presented here are related to STN stimulation. A total of 1270 seizures were induced during 31 sessions in 2 primates. The occurrence of first seizure was significantly delayed as compared to sham situation. Total time spent in focal seizures was significantly reduced by 60% on an average (p 0.05) after STN stimulation, due to a significant decrease in the number of seizures especially so during the first 3 hours after stimulation. The duration of individual seizures reduced moderately. There was a trend of a decrease in interictal spikes during ON stimulation. Bipolar and monopolar stimulation modes were equally effective.Conclusions: This study provides rationale and initial original results in primates showing the potential therapeutic effect of chronic HFS-STN DBS to treat pharmacoresistant focal motor seizures.