Abstracts

Rationale: Prior research from our laboratory and others indicated that current controlled low frequency sine-wave stimulation reduced the likelihood of evoked seizures by >50% and increased the afterdischarge threshold by >200% in the kindling model of epilepsy. These initial data suggested that this type of stimulation may be effective for treating epilepsy. This stimulation has the following core features that distinguish it from stimulation strategies being tested clinically: 1) low frequency oscillation, 2) long pulse widths, 3) no interpulse delay, and 4) longer burst durations. In this study, we used a 12-cage, 24-hour EEG monitoring system to evaluate the efficacy of voltage controlled low frequency stimulation (VCLFS) on spontaneous electrographic seizures and interictal events in the rat tetanus toxin (Tx) and pilocarpine (Pilo) models of mesial temporal lobe epilepsy (MTLE). Electrographic seizures were identified using a new audio transformation method (see Breeden et al. poster at this meeting). Methods: Bipolar, platinum-iridium electrodes were implanted bilaterally into the hippocampus of male, Sprague-Dawley rats. For Tx rats, the Tx was injected into the right ventral hippocampus (50ng, 0.5µl) at the same time as electrode implantation. For Pilo rats, status epilepticus (SE) was induced (365mg/kg/s.c.) one week after electrode implantation. Tx rats were allowed to recover 2 weeks and Pilo rats 4 weeks before being placed in individual recording chambers and connected to a cable-commutator system. Electrographic seizure rates were measured during Baseline and Treatment periods using a 24-hour EEG monitoring system. Hippocampal EEG data were collected and used to determine electrographic seizure rates. Baseline seizure rates were determined for 5 days (Tx) or 10 days (Pilo). Then therapy was initiated and Treatment seizure rates were measured during an equal period of time. For both models, control animals were not stimulated. Treatment animals received VCLFS (1 Hz, 500 ms/phase, ± 1 V). VCLFS was delivered continuously for 60 s of each hour. Results: Significant decreases in electrographic seizure rates (p <0.05) were observed in response to VCLFS (n=16) compared to no therapy controls (n=7) in Tx model. Decreases were also observed in electrographic seizure rates in the Pilo spontaneous seizure model, however the sample sizes for this model are currently too small for statistical comparison. Data collection for the Pilo model is ongoing. Conclusions: These data indicate that scheduled VCLFS focal stimulation can decrease electrographic seizure rates in animal models of MTLE. These data also demonstrate that the Tx and Pilo spontaneous seizure models can be used to evaluate the effect of stimulation. (Supported by NINDS 5U01NS064049)