Abstracts

Rationale: Low Frequency Electrical Stimulation (LFES) has proven to be effective as an alternative treatment for refractory epilepsy. However, LFES requires brain surgery and deep implantation of electrodes in the brain. We investigated whether a non-invasive implementation of this method using low frequency sensory stimulation (LFSS) could provide an effective alternative to surgical resection or electrical stimulation for temporal lobe epilepsy. Methods: Two animal models of Mesial Temporal Lobe Epilepsy (MTLE) were implemented in order to assess the effect of Low Frequency Audio-Visual stimulation on the frequency and duration of seizures. Stimulation was presented in the form of 1-Hz flashing light and clicking sound. EEG recordings were obtained a week prior to stimulation and compared against EEG recordings during stimulation. Histological studies using chromogenic and immnuno staining were performed in order to quantify the cellular correlate of the stimulation and explore potential molecular mechanisms resulting from stimulation. Results: In the kindling model, a 75% reduction in seizures per hour per day was observed p<0.001 (from a baseline of 0.63 ± 0.05 seizures/hour to 0.16 ± 0.15 (N=2)), while in the kainic acid model LFSS produced a reduction of 55% p<0.001 (from a baseline of 0.50 ± 0.34 seizures/hour to 0.23 ± 0.27 (N=8)). The duration of seizures was also significantly reduced in both models, (38% reduction in the kindling model and by 47% in the kainic acid model). Animals receiving LFSS showed greater counts in the CA3 region compared to controls (p < 0.012), suggesting sensory stimulation prevents neural death. Expression of Sonic Hedgehog (SHH) was found to decrease post-stimulation by 60% and the number of CA1 neurons expressing SHH was also significantly higher after stimulation (p < 0.001) suggesting the possibility that LFSS induced lasting plastic effects in the brain. Conclusions: Significant reduction of seizure frequency/duration indicates that 1-Hz sensory stimulation can significantly decrease excitability and frequency of seizures in the hippocampus. The effect of the stimulation on the expression of molecular markers for MTLE provides a cellular correlate basis for the efficacy of this non-invasive intervention modality.