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 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 R=3 myoclonic jerk. Control rats were prepared and treated the same way except that no current was passed through the electrodes. Behavior was scored as follows: the stages are: R=0, no seizure activity; R=1, oral-facial movements only; R=2, head nodding; R=3, myoclonic jerks; R=4, forelimb clonus; R=5, rearing. The duration of the behavioral signs of seizure activity was measured as time elapsed between the first and last myoclonic jerk. For a within-subjects comparison, the TcES treated rats were also tested as controls one to two days after the TcES treatment. Results: In the control group, the rats exhibited myoclonic jerks (R=3) with a latency of less than 5 min and then progressed from myoclonic jerks through rearing with forelimb clonus; repeated seizure episodes were observed over a 20 min period. Electrographic signs of seizure activity, (short high-frequency bursting) preceded the behavioral activity and typically continued for over an hour after the behavioral activity had ceased. The duration over which behavioral signs of seizure activity occurred was compared between the control group and the TcES treated group. There was a significant (p=0.001) reduction in this duration as a result of treatment: TcES treated, 7 min (n = 14) vs Controls, 19 min (n = 21). Moreover, all controls progressed through various seizure stages, reaching a maximum of R =5 or 6. In contrast, after TcES, no behavioral activity was evident in 6 treated rats and only a few myoclonic jerks were observed in the remaining treated rats. In most of the treated rats, the electrographic seizure activity resolved within 1 min after TcES application. Conclusions: TcES applied over the scalp, via concentric ring electrodes, significantly attenuated seizures 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, these results indicate that the seizure control achieved with noninvasive TccES 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.