Abstracts

Rationale: Sudden Unexplained Death in Epilepsy (SUDEP) is a well-recognized cause of death in patients with epilepsy, especially patients with medically intractable seizures. Estimated SUDEP rates are 5.9/1,000 years in patients with medically refractory epilepsy[1], 6.9 (95% CI: 3.8-11.6) /1000 patient years in patients in the placebo arm of randomized controlled trials of antiepileptic medications[2] and 9.3/1000 in candidates for epilepsy surgery[3]. Patients being considered for treatment with the RNS System are most clinically similar to this latter group. In order to provide information about the rate of SUDEP, rates were calculated in adults with medically intractable partial onset seizures arising from one to two seizure foci who were treated with brain-responsive stimulation with the RNS System. [1] Nashef, L., Fish, D.R., Sander, J.W., Shorvon, S.D., 1995. Incidence of sudden unexpected death in an adult outpatient cohort with epilepsy at a tertiary referral centre. J Neurol Neurosurg Psychiatry . 58; 462?"464. [2] Ryvlin, P., Cucherat, M., Rheims, S., 2011. Risk of sudden unexpected death in epilepsy in patients given adjunctive antiepileptic treatment for refractory seizures: a meta-analysis of placebo-controlled randomised trials. Lancet Neurol. 10; 961?"968. doi:10.1016/S1474-4422(11)70193-4. [3] Dasheiff, R.M., 1991. Sudden unexpected death in epilepsy: a series from an epilepsy surgery program and speculation on the relationship to sudden cardiac death. J Clin Neurophysiol. 8; 216?"222. Methods: SUDEP rates were calculated for patients being treated with brain responsive stimulation (RNS System, NeuroPace, Mountain View, CA) for medically intractable partial onset seizures. Rates were calculated for all patients treated with the RNS System, including those treated within the clinical trials and in the post-market setting. Instances of death were adjudicated by an independent SUDEP Analysis Committee and reviewed by an independent Data Monitoring Committee. Those determined to be "probable SUDEP" and "definite SUDEP" were included in the analysis. Data cutoff was on 05/05/2016. Results: For all patients treated with the RNS System (n=707), the SUDEP rate was 2.3/1,000 (95% CI: 0.9-5.4) over 2,208 patient implant years and 2.0/1,000 (95% CI: 0.7-5.2) over 2,036 patient stimulation years. Conclusions: The potential impact on the risk for SUDEP is an important consideration when evaluating epilepsy treatments. This report evaluated the rate of probable and definite SUDEP for patients with medically intractable partial onset seizures treated with brain responsive stimulation. The upper limit of the 95% CI for patients being treated with brain responsive neurostimulation is not elevated above the estimated rate for patients with medically intractable epilepsy. Moreover, the upper limit is below that of patients with medically intractable seizures who are candidates for epilepsy surgery and of patients randomized to the placebo arm of antiepileptic medication trials. Funding: None.