Abstracts

Rationale: Hippocampal deep brain stimulation (DBS) is an experimental therapy for patients with pharmacoresistant temporal lobe epilepsy (TLE). No studies have investigated the anti-epileptogenic potential of hippocampal DBS. In this animal experimental study, we evaluated the effect of hippocampal DBS on the development of spontaneous seizures in the systemic kainic acid rat model. Methods: Rats were implanted with a quadripolar DBS/EEG-registration electrode in the right hippocampus and a bipolar EEG recording electrode in the left hippocampus. 24 hours after kainic acid (KA) induced status epilepticus (SE), one group (n=6) was subjected to short term DBS (ST-DBS) (Poisson Distributed Stimulation, 130 PPS, 100µs PW, 100µA) of 1 week, a second group (n=7) was subjected to long term DBS (LT-DBS) (PDS, 130 PPS, 100µs PW, 100-400µA) of 10 weeks. A control group (n=9) received sham stimulation (SHAM). EEG was recorded continuously during 14 weeks in the LT-DBS and SHAM group. In the ST-DBS group, EEG was recorded continuously during 8 weeks. Results: The gradual increase in mean daily seizure frequency following SE was significantly lower in the LT-DBS group compared to the SHAM group (p<0.01). While seizure frequency increased from 0.1 ± 0.1 seizures per day in week 1 to 10.3 ± 1.3 seizures per day in week 10 in the SHAM group, this increase was not observed in the LT-DBS group (0.5 ± 0.1 seizures per day in week 1 versus 1.2 ± 0.4 seizures per day in week 10). When DBS was stopped in the LT-DBS group seizure frequency remained low (4.14 ± 1 seizures per day in week 14), while in the SHAM group it continued to increase (26.6 ± 3.1 seizures per day in week 14). In the ST-DBS group there was no significant difference in mean daily seizure frequency increase compared to the SHAM group. Conclusions: Long term hippocampal DBS reduces the gradual increase in seizure frequency in a rat model for temporal lobe epilepsy. These findings strongly support the hypothesis that hippocampal DBS affects epileptogenesis.