{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T21:50:28Z","timestamp":1792273828193,"version":"4.4.0"},"reference-count":22,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2026,8]]},"abstract":"Abstract<\/jats:title>\n \n Objective<\/jats:title>\n This study was undertaken to evaluate the safety and effectiveness of responsive thalamic stimulation as adjunctive therapy for drug\u2010resistant idiopathic generalized epilepsy (IGE) with generalized tonic\u2013clonic seizures (GTCSs).<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n NAUTILUS is a prospective, multicenter, single\u2010blind, randomized sham\u2010controlled pivotal trial. Patients were \u226512\u2009years of age with drug\u2010resistant IGE and \u22652 GTCSs over a 3\u2010month baseline. Bilateral depth leads were targeted to the centromedian thalamus. One month later, patients were randomized to Active (responsive stimulation,\n n<\/jats:italic>\n \u2009=\u200944) or Sham (no stimulation,\n n<\/jats:italic>\n \u2009=\u200943). The effectiveness evaluation period (EEP) began 3\u2009months postimplant through 1\u2009year. After a second GTCS in the EEP, patients transitioned to open\u2010label active stimulation. The primary safety endpoint was the serious adverse device\u2010related event (SADE) rate at 84\u2009days postimplant. The primary effectiveness endpoint was time\u2010to\u2010second\u2010GTCS during the EEP. Additional endpoints included median percent change in days with any generalized seizure, GTCS frequency, and responder rate (RR).\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Eighty\u2010seven patients were implanted across 23\u2009US centers. The SADE rate was significantly below the performance goal (6.9%,\n p<\/jats:italic>\n \u2009<\u2009.0001), with no adverse effects on cognition, mood, or sleep. The prespecified primary effectiveness endpoint was not significant. However, a post hoc mixed\u2010effects model considering all EEP days demonstrated greater GTCS reduction in the originally randomized Active group (61%) compared to patients originally randomized to Sham (49%,\n p<\/jats:italic>\n \u2009=\u2009.030). Eighteen\u2010month outcomes included 76.8% median GTCS reduction, 62.5% RR, 40% GTCS\u2010free at that timepoint, and 77.8% median reduction in days with any generalized seizure. More than 90% of patients and 86% of physicians reported improvement on Global Impression of Change scales.\n <\/jats:p>\n <\/jats:sec>\n \n Significance<\/jats:title>\n NAUTILUS is the first randomized controlled neuromodulation trial in IGE. Responsive thalamic stimulation provided a clinically meaningful and durable reduction in seizures with an acceptable safety profile, offering a much\u2010needed option for drug\u2010resistant IGE.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/epi.70321","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T14:39:36Z","timestamp":1780497576000},"page":"4139-4152","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Responsive stimulation of the thalamus for idiopathic generalized epilepsy: Results of the randomized controlled\n NAUTILUS<\/scp>\n trial through 18\u2009months"],"prefix":"10.1002","volume":"67","author":[{"given":"Utku","family":"Uysal","sequence":"first","affiliation":[{"name":"The University of Kansas Hospital Kansas City Kansas 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