Abstracts

Rationale: Electrical stimulation of discrete brain structures is an emerging treatment modality for patients with pharmacoresistant epilepsy. Although several clinical and experimental studies attempted to determine specific stimulation targets in the brain, no clear clinical applications have been described. This study was conducted to investigate the therapeutic effect of low amplitude, low frequency, open loop, frontal neocortical electrical stimulation on an animal model of generalized epilepsy.Methods: Fifty to sixty day-old, adult male Sprague-Dawley rats (n=18) were used for the experiments. Ten rats in the “stimulation” and 8 rats in the “control” group were randomly assigned. Six epidural screw electrodes (1 anterior frontal midline, 2 lateral frontal, 2 lateral parietal and 1 occipital/cerebellar midline) were implanted sterotactically. Bilateral frontal screw electrodes were used as stimulation electrodes in the stimulation group. Following 48 hours of recovery period, 1.5 mA, 1 Hz bipolar electrical stimulation was delivered to the stimulation group for 24 hours. Control rats did not receive electrical stimulation. After the 24 hours of stimulation, 10-15 minutes baseline video/EEG recordings were obtained and then 60 mg/kg PTZ was injected intraperitoneally. Video/EEG recordings were continued for one hour for each animal. Recordings were analyzed electrographically and visually. Latency to the first electrographic epileptiform abnormality, clinical severity of the seizures, and the duration of epileptic EEG abnormalities were determined. Clinical seizure types were classified as Absence-like episodes (A) only, Myoclonic (M) seizures ± A and generalized clonic (GC) ± M ± A seizures. The total duration of EEG-confirmed epileptic abnormalities was scored based on the percentage of the epileptic changes during the one hour period: 1= 0-25% of abnormal EEG; 2= 25-50% of abnormal EEG; 50-75% of abnormal EEG and 4=75-100%of abnormal EEG.Results: We found that low frequency/low amplitude cortical electrical stimulation significantly delayed the EEG seizure onset (p<0.05) (Figure 1). When seizures occurred in the stimulated rats, they were lighter (A only) versus more severe myoclonic and/or generalized clonic seizures in the control animals (Figure 2). Duration of epileptic EEG abnormalities was significantly shorter in the stimulation group as compared to the control group (p<0.05). Average score of EEG abnormalities were 1.6 ± 0.84 and 2.75 ± 0.71 respectively.Conclusions: Our findings suggest that low frequency low amplitude electrical stimulation of frontal cortex have a significant effect on a rat model of generalized epilepsy. Further studies using various doses of PTZ injections as well as different seizure models, such as focal cortical epilepsy, would confirm these results.