Abstracts

Rationale: Transcutaneous electrical stimulation (TcES) via concentric ring electrodes was previously shown to attenuate seizure behavior and electrographic activity induced by pilocarpine [Besio et al. Epilepsia 2007]. Here we evaluated the effect of TcES on the electrographic activity of seizures induced by pentylenetetrazole (PTZ) in rats. Methods: Male Sprague-Dawley rats weighing 290-330gms were briefly anesthetized, shaved and concentric ring electrodes were attached to their scalp one day before the experiment. PTZ (45mg/kg) was given intraperitoneally. Laplacian EEG was recorded from tri-polar concentric electrodes on the scalp. TcES (50 mA, 300 Hz, 200 uS for 2 min) was applied directly after the first myoclonic jerk (Racine’s scale: R=3). The power spectrum of the electrographic activity was calculated for: (a) the baseline activity (prior to administering the PTZ), (b) 25 sec prior to applying the TcES, and (c) 25 sec after applying the TcES. For the control group (c) was an estimate of the 25 sec taken 2 min after the first myoclonic jerk, which is an estimate of when TcES would have been stopped. The power spectra were compared statistically with a single-factor ANOVA and then Bonferroni corrected t-tests. Results: In both the TcES treated and control groups, the rats exhibited myoclonic jerks (R=3) with a latency of less than 2 min. Electrographic signs of seizure activity, preceded the behavioral activity and typically continued for at least 30 min. There was a significant difference between the combined: baseline, before TcES, and after TcES power spectra for TcES treated rats (p= 9.8033e-14) and controls (p=1.55e-19). For the TcES treated rats there was no significant difference between the power spectra of the baseline and after TcES (p=0.143) and there was between both power spectra of the baseline and after TcES compared to before TcES (p<0.01, p<0.01). In the control group, there was a significant difference between the baseline power spectra and both the before when the TcES would have been administered and after TcES would have been administered (p<0.01, p<0.01). However, there was no significant difference between the spectra for just before TcES and just after TcES (p=0.4368). The power spectra for the control group continued to increase over time until the effects of the PTZ lessened. Conclusions: TcES applied on the scalp, via concentric ring electrodes, significantly attenuated power spectra of electrographic seizure activity induced by PTZ; this treatment was effective in suppressing seizures even when administered after onset. Taken together with previous effects observed in models of status epilepticus induced by either pilocarpine or penicillin G, and behavioral activity induced by PTZ these results indicate that the seizure control achieved with noninvasive TcES is applicable to diverse seizure types and mechanisms of seizure induction. These results also suggest that in the future TcES has the potential to be a viable non-invasive therapy for intractable epilepsy.