Abstracts

The need for novel, efficacious anti-seizure therapies is widely acknowledged. Seizures may be blocked by electricity if delivered in close proximity to their onset. This study investigates in humans, the feasibility, safety and efficacy of high frequency stimulation (HFES; 100-500 Hz.) triggered by automated seizure detections. Eight subjects undergoing surgical evaluation were enrolled in this study, which consisted of a control (CP) and an experimental phase (EP). HFES was delivered to the epileptogenic zone (Local-closed loop; LCL) to 4 subjects and to the anterior thalamic nuclei of the other four (Remote-closed loop; RCL). Seizures were detected and quantified using a validated algorithm. Interphase (CP vs. EP) and intra-phase (stimulated vs. non-stimulated seizures) comparisons of clinical seizure frequency ([italic]Sf[/italic]) and relative seizure severity (RSS; clinical and electrographic) were performed and differences assessed using effect size (ES). Subjects were deemed [quot]responders[quot], if [italic]Sf[/italic] was reduced by at least 50% and [quot]non-responders[quot] if not. All subjects completed the study; rescue medications were not required. There were a total of 1491 HFES (0.2% triggered after-discharges). Mean decrease in [italic]Sf[/italic] in the LCL group was 55.5% (-100 to +36.8%); (3/4 [quot]responders[quot]: 86% (-100 to -58.8%)) and in the RCL 40.8% (-72.9 to +1.4%) (2/4 [quot]responders[quot]: 74.3% (-75.6 to -72.9%). Effect size on RSS was 0 in the LCL ([quot]responders[quot]: medium to large in magnitude) and negligible in the RCL group ([quot]responders[quot]: medium to large). HFES effects on epileptogenic tissue were immediate and also long-lasting. This is the first study in the history of epileptology to demonstrate the feasibility and short-term safety of closed-loop anti-seizure therapy and provide preliminary evidence of efficacy. (Supported by Medtronic, Inc. and the Kansas Technology Enterprise Corporation)