MORE Than Meets the Eye: The Evolving Landscape of DBS in Epilepsy

Long-Term Evaluation of Anterior Thalamic Deep Brain Stimulation for Epilepsy in the European MORE Registry Kaufmann E, Peltola J, Colon AJ, Lehtimäki K, Majtanik M, Mai JK, Bóné B, Bentes C, Coenen V, Gil-Nagel A, Goncalves-Ferreira AJ, Ryvlin P, Taylor R, Brionne TC, Gielen F, Song S, Boon P; MORE study group. Epilepsia. 2024;65(8):2438-2458. doi: 10.1111/epi.18003 Objective: Short-term outcomes of deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) were reported for people with drug-resistant focal epilepsy (PwE). Because long-term data are still scarce, the Medtronic Registry for Epilepsy (MORE) evaluated clinical routine application of ANT-DBS. Methods: In this multicenter registry, PwE with ANT-DBS were followed up for safety, efficacy, and battery longevity. Follow up ended after 5 years or upon study closure. Clinical characteristics and stimulation settings were compared between PwE with no benefit, improvers, and responders, that is, PwE with average monthly seizure frequency reduction rates of ≥50%. Results: Of 170 eligible PwE, 104, 62, and 49 completed the 3-, 4-, and 5-year follow up, respectively. Most discontinuations (68%) were due to planned study closure as follow up beyond 2 years was optional. The 5-year follow-up cohort had a median seizure frequency reduction from 16 per month at baseline to 7.9 per month at 5-year follow up ( P < .001), with most-pronounced effects on focal-to-bilateral tonic–clonic seizures (n = 15, 77% reduction, P = .008). At last follow up (median 3.5 years), 41% (69/170) of PwE were responders. Unifocal epilepsy ( P = .035) and a negative history of epilepsy surgery ( P = .002) were associated with larger average monthly seizure frequency reductions. Stimulation settings did not differ between response groups. In 179 implanted PwE, DBS-related adverse events (AEs, n = 225) and serious AEs (n = 75) included deterioration in epilepsy or seizure frequency/severity/type (33; 14 serious), memory/cognitive impairment (29; 3 serious), and depression (13; 4 serious). Five deaths occurred (none were ANT-DBS related). Most AEs (76.3%) manifested within the first 2 years after implantation. Activa PC depletion (n = 37) occurred on average after 45 months. Significance: MORE provides further evidence for the long-term application of ANT-DBS in clinical routine practice. Although clinical benefits increased over time, side effects occurred mainly during the first 2 years. Identified outcome modifiers can help inform PwE selection and management.