Abstracts

Rationale: Treatment of obstructive sleep apnea (OSA) in patients with epilepsy appears to improve seizure control and daytime sleepiness, although studies have been small and non-controlled. The goal of this pilot study was to refine design issues prior to embarking on a Phase III Trial of treating OSA in patients with epilepsy.Methods: Adults with refractory epilepsy (2 or more seizures per month) were enrolled into the trial if they met study criteria, including a history suggestive of OSA. After polysomnography (PSG) confirmed OSA, subjects were randomized to treatment with either therapeutic or sham continuous positive airway pressure (CPAP). Subjects were maintained on stable doses of antiepileptic medications and CPAP adherence was monitored with electronic cards.Results: Of 43 subjects undergoing PSG, 36 met criteria for OSA, defined by an apnea-hypopnea index (AHI) of 5 or more events per hour (81% true positive rate). The first night of PSG appeared sufficient for diagnosing OSA, with only one subject having OSA on night 2 (AHI 5.8) but not on night 1 (AHI 3). 22 subjects were randomized to therapeutic CPAP (with 19 completers) and 13 subjects to sham CPAP (all completed the trial). Adherence was similar in the therapeutic and sham groups (71.8% of nights, 4.4 hours per night) and significantly higher in adults ages 45 or older (5.4 hours, p = 0.01 by independent two-tailed t-test). Subjects, coordinators, and PIs were not able to distinguish therapeutic from sham CPAP (kappa values < 0.40). A 50% or greater reduction in seizures was observed in 32% of the subjects in the therapeutic group as compared to 15% of those in the sham group.Conclusions: Treatment of obstructive sleep apnea in epilepsy appears promising in reducing seizure frequency, and a Phase III randomized multicenter clinical trial employing therapeutic and sham CPAP appears feasible. This trial was supported by NINDS R01 NS42698 and the General Clinical Research Centers at University of Michigan (M01-RR00042), University of North Carolina-Chapel Hill (M01-RR00146) and Vanderbilt University (M01-RR00095)