Abstracts

Brain stimulation is currently being developed as a new therapy for epilepsy. We have previously reported that preemptive low frequency (LF) sine wave stimulation significantly decreased the incidence of amygdala and hippocampal kindled seizures (SZ) in the rat (Goodman et al., 2005). Preemptive LF square wave stimulation was ineffective. In this study we compared the effectiveness of LF square to LF sine wave stimulation when the putative therapeutic stimulus was delivered postictally. Bipolar, Teflon-coated stainless steel electrodes were implanted bilaterally into the basolateral amygdalae of adult, male Sprague-Dawley rats (275-350g; n=7). After a one week recovery, afterdischarge (AD) threshold was determined and the animals were stimulated once/day with the following stimulus: 60Hz, 1msec pulse, 400[mu]A sine wave for 1sec. Animals were kindled 5days/week and stimulation was continued until the animals were fully kindled. Each animal received an additional 10 stimulations to determine a baseline SZ frequency. To test the effectiveness of postictal stimulation the LF square or LF sine wave stimulus was delivered 90sec after the end of kindled SZ AD. The LF square wave stimulus was: 1Hz, 1msec, 50[mu]A for 15min. The LF sine wave stimulus was: 1Hz, 50[mu]A for 1min. The effectiveness of LF square wave stimulation was tested once/day for 10 days. Upon completion, the effectiveness of the postictal LF sine wave was tested in the same animals twice/day, for a total of 20 stimulations/rat. When a kindled SZ failed to occur the low frequency stimulus was delivered 90sec after the kindling stimulus. Postictal LF wave stimulation had no effect on the incidence of stage 5 amygdala kindled SZ while postictal LF wave stimulation significantly decreased the incidence of stage 5 SZ by 40% (Chi-Square; p[lt]0.03). The anticonvulsant effect of the postictal LF sine wave stimulus was graded; although animals failed to exhibit stage 5 SZ, seizures with lower behavioral scores often occurred. The LF sine wave stimulus became more effective as the number of stimulations increased suggesting a cumulative effect. This differed from the response to preemptive LF sine wave stimulation which usually resulted in a complete block of the kindled SZ when effective. The effect of the postictal LF sine wave stimulation did not appear to be long lasting; when stimulation was discontinued for two days the subsequent kindling stimulation elicited a stage 5 SZ in 6/7 animals. These results provide further evidence that low frequency sine wave stimulation may be an effective new therapy for epilepsy. The mechanism responsible for this anticonvulsant effect is unknown but it appears to involve a depotentiation-like process. Further studies are required to determine if altering the stimulus parameters will increase the effectiveness of LF sine wave stimulation. (Supported by NeuroPace, Inc., the Cure Foundation and the Helen Hayes Hospital Foundation.)