Abstracts

Rationale: Cathodal transcranial direct current stimulation (tDCS) is a noninvasive method for regional suppression of cortical excitability. Cathodal tDCS is well-tolerated, inexpensive, may be applied in minutes, and in limited studies appears to increase the seizure threshold. Yet the capacity of tDCS to suppress ongoing seizures, such as those of status epilepticus (SE), has not been tested. To evaluate a possible role for tDCS in the treatment of SE, we tested its anticonvulsive effect on high dose pentylenetetrazol (PTZ)-induced seizures in rats. Methods: Restrained unanesthetized rats were injected intraperitoneally with PTZ (75 mg/kg) while monitored by continuous video-EEG. Following PTZ injection, and one minute after the first myoclonic jerk, 1 mA (n=9) or 0.1 mA (n=9) cathodal tDCS was applied for 20 minutes. A control group received sham tDCS. Rats were then monitored by video EEG for another 10 minutes after which time a second PTZ dose (20 mg/kg. Video EEG continued for another 15 minutes after the second PTZ dose. Results: All groups had similar latencies to the first myoclonus and the first generalized tonic-clonic seizure (GTCS). However, the initial GTCS was significantly shorter in the 1 mA tDCS than in the sham group (21.4 secs vs. 32 secs; p = 0.02). 3/9 rats in the sham group died after the first PTZ injection and 1/9 died in each of the two stimulated groups. The second PTZ challenge induced a GTCS in 6/6 surviving sham rats, in 4/8 of the surviving rats in the 1 mA group and in 6/8 rats in the 0.1 mA group (p < 0.001). Compared to sham, latency to GTCS following second PTZ injection was longer in the 1 mA tDCS group (p = 0.02) and in the 0.1 mA (p = 0.04) groups. The second GTCS duration was also significantly shorter in the 1 mA group (32 secs) as compared to sham (59 secs; p = 0.03). Conclusions: Cathodal tDCS, delivered during the acute ictal state, appears effective in suppressing seizures in the PTZ rat model. Given its favorable safety profile, these data suggest a possible role for tDCS in the treatment of ongoing seizures such as those of SE.