Abstracts

Rationale: Focal electrical neurostimulation is an emerging adjunctive therapy for medically refractory epilepsy. While this therapy may be determined by FDA to be clinically safe and efficacious, the stimulation parameters (frequency, pulse width, burst duration) have yet to be systematically evaluated. In this rat study, we used a newly developed 12-cage, 24-hour video/EEG monitoring system to evaluate the efficacy of low frequency (LFS) and high frequency (HFS) stimulation on spontaneous electrographic seizures and interictal events in the tetanus toxin (Tx) and pilocarpine (Pilo) models of mesial temporal lobe epilepsy.Methods: Bipolar, platinum-iridium electrodes were implanted bilaterally into the ventral hippocampus of male, Sprague-Dawley rats. For Tx rats, the Tx was injected into the right ventral hippocampus (50ng, 0.5 l) 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. Seizure rates were measured during Baseline and Treatment periods using a 24-hour video/EEG monitoring system. Video detection of behavioral seizures was performed using SeizureScan software (Cleversys Inc.). 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. Experimental animals received LFS (1 Hz, 500 ms/phase, 1 V) or HFS (200 Hz, 60 s biphasic pulse, 100-400 A/phase, 100 ms burst duration). LFS was delivered continuously for 60 s of each hour. HFS was delivered in response to epileptiform activity detected by the NeuroPace, Inc. RNS System neurostimulator. Detection was customized for each subject.Results: This new system allowed for the 24-hour recording of electrographic and behavioral events as well as the delivery of either continuous scheduled or responsive stimulation. Decreased electrographic seizure rates were observed in response to LFS or HFS in both spontaneous seizure models. Conclusions: These data indicate that scheduled LFS and responsive HFS focal stimulation can decrease seizure rates in animal models of mesial temporal lobe epilepsy. These data also demonstrate that the Tx and Pilo spontaneous seizure models can be used to evaluate the effect of different stimulation parameters. This is the first time that LFS has been evaluated in rodent models of spontaneous seizures. (Supported by NINDS 1U01NS064049-01A1).