Abstracts

Rationale: Bilateral deep brain stimulation (DBS) of the anterior nuclei of the thalamus (ANT) is an effective treatment for partial epilepsy. Initial response was positive (Fisher et al, Epilepsia, 51:899, 2010) and efficacy increased over a 5-year period (Salanova et al, Neurology, 84:1017, 2015). This is a report of the safety and effectiveness for patients in the SANTE trial with at least 7 years of follow-up. Methods: The Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy (SANTE) study was a prospective, multicenter, double-blind, randomized, controlled trial of bilateral DBS of the ANT in 110 implanted subjects (109 were randomized). Primary analysis was performed on subjects with at least 70 days of seizure diary data. Intent-to-treat sensitivity analyses assessed the potential impact of missing data including last observation carried forward (LOCF) and worst case (WC; missing data imputed to 100% worsening from baseline). A constant cohort (CC) analysis was also performed. Results: The median percent seizure frequency reduction from baseline was 41% at 1 year (n=99) and 75% at 7 years (n=50) (both p < 0.001). Sensitivity analyses showed median seizure reduction at 7 years of 70% (n=109) using LOCF, 76% (n=62) using CC, and 39% (n=109) using WC. Median seizure reduction at 7 years was 78% for complex partial (n=44; p < 0.001), 71% for partial to generalized (n=20; p < 0.05), and 71% for most severe (n=30; p < 0.001) seizure types. There were 74 subjects who added at least 1 new antiepileptic drug (AED) between implant and year 7. Seizure reduction was similar for subjects with and without medication additions, although less improvement was observed in those who added AEDs. The responder rate (?-50% seizure reduction) was 43% at 1 year and 74% at 7 years. Twenty subjects (18%) experienced at least one 6-month remission period between implant and year 7. At 7 years, 9 subjects were seizure-free for the preceding 6 months, 9 for the preceding 1 year, and 8 for the preceding 2 years. The Liverpool seizure severity scale and quality of life measure (QOLIE-31) showed statistically significant improvements from baseline at year 7 (n=67; p < 0.001 for both measures). The 110 subjects have accumulated 713 device years of experience. There were no unanticipated adverse device effects, and 1 report of symptomatic intracranial hemorrhage attributed to a seizure-related fall and not considered device-related. The most frequent serious device-related adverse events included implant site infection (10.9%) and leads not in target (8.2%). Conclusions: Many partial epilepsy patients achieved sustained reduction in seizure frequency with bilateral DBS of the ANT. The risks of DBS therapy have been well-characterized during this follow-up period. Funding: Medtronic, Inc. sponsored the study and funded the trial.