Abstracts

RATIONALE: Evidences from animal studies suggest the existence of a nigral control system of epilepsy, and the subthalamic nucleus (STN) is considered to be a target site to activate this seizure inhibitory system. In previous studies, chemical or electrical inhibition of bilateral STN suppressed seizures, but the unilateral procedures showed no effect. We hypothesized unilateral STN inhibition suppressed the ipsilateral neocortical seizures and examined the antiepileptic effect of STN inhibition on a neocortical seizure model.
METHODS: A cannula was implanted into the left motor cortex in eight male Wistar rats. The animals were implanted monopolar electrodes in bilateral motor cortices for EEG recording and a bipolar electrode in bilateral STN for electrical stimulation. Focal motor seizures were induced by an infusion of 2.0 [mu]g of kainic acid via the cannula. During the seizure status, continuous STN stimulation for 40 minutes was performed repetitively with a resting interval of 20 minutes. The stimulation parameters were biphasic square pulse with 0.1 ms width and 130 or 500 Hz of frequency. The intensity was set to 70% of the threshold of motor symptom. The antiepileptic effect was analyzed by changes in seizure frequency and spike frequency that was calculated using a video-EEG system. The data was compared between the stimulation period and the resting intervals. In another experiment, the animals were implanted a cannula into the left STN in exchange for the stimulation electrode. During seizure status, 200 ng of muscimol was infused into STN, and the effect on seizures was studied. The behavior of the animal was observed for seven days after the procedures, and then the animals were sacrificed and examined histopathologically.
RESULTS: Three of the eight animals were removed from this study because of incorrect location of the electrodes or different parameters of the stimulation. In five animals, the seizure frequency decreased during the STN stimulation period compared with that during the non-stimulation interval period. When the stimulation was stopped, seizures occurred frequently. The seizure frequency during ipsilateral STN stimulation of 130 Hz was only 55% of the non-stimulation intervals, and ipsilateral stimulation of 500 Hz also reduced seizure frequency to 66%. Bilateral stimulation of 130 Hz reduced seizure frequency to 60%. There was no remarkable difference between the frequencies of interictal spikes in the stimulation and non-stimulation periods. None of the animals showed abnormal behavior during or after STN stimulation. Infusion of muscimol into STN rapidly inhibited the seizure status. EEG became to show only interictal spikes, and neither clinical nor electrographical seizures occurred thereafter. However, behavioral change of the animals was observed that they were circling to the right backward and then searching. These abnormal behaviors were lasted for 3 to 6 hours.
CONCLUSIONS: Our results revealed that not only bilateral but also unilateral inhibition of STN could suppress focal neocortical seizures. STN stimulation may be useful as a new therapeutic procedure for not only primary generalized seizures but also unilateral focal seizures that elicited from surgical unrespectable cortex.