Temporal lobe epilepsy is one of the most difficult to treat forms of epilepsy. One third of the patients is or becomes refractory to anti-epileptic drugs, emphasizing the need for new therapeutic strategies, among which hippocampal deep brain stimulation (DBS). In this study we compare the efficacy of two stimulation paradigms: Poisson distributed stimulation (PDS) is compared with High Frequency Stimulation (HFS) in the kainic acid model, a validated model for human temporal lobe epilepsy.

Status epilepticus (SE) was induced by intraperitoneal injection of kainic acid, leading to epileptogenesis. After fifty days, rats with spontaneous seizures were implanted with depth stimulation and recording electrodes in the hippocampus. After 15 days of continuous baseline EEG monitoring, 13 rats received continuous PDS (mean frequency 130 Hz) and 11 received regular HFS (fixed frequency of 130 Hz) during the following 10 days. The maximum stimulus intensity at which rats could be stimulated without experiencing EEG and/or behavioral side effects was significantly lower for PDS than for HFS (p<0.02). Seizure frequency and seizure duration were continuously monitored before, during and after PDS and HFS.

Seven out of 13 rats (54%) treated with PDS and 5 out of 11 rats (45%) treated with HFS experienced a significant reduction in seizure frequency and were considered responders. In them seizure frequency was reduced with 67% from baseline (p<0.01) during PDS and with 50% from baseline (p<0.01) during HFS. None of the stimulation modalities affected mean seizure duration. After termination of the stimulation, the effect induced by PDS faded away in days restoring seizure frequency to its pre stimulus levels. The other 12 non-responder rats did not demonstrate any reduction in seizure frequency.

We conclude that continuous hippocampal PDS with a mean frequency of 130 Hz is an interesting new stimulation paradigm, which significantly reduces spontaneous seizure frequency in a large fraction of the epileptic rats. Its efficacy, even at a lower stimulus intensity, is larger than that of the equivalent regular HFS at 130 Hz.