Seizure outcomes after thalamic deep brain stimulation in drug-resistant epilepsy: How electrode location, device platform, and epilepsy subtype drive response-A systematic review with pooled analysis.

Abstract

Deep brain stimulation (DBS) targeting the anterior nucleus of the thalamus (ANT), centromedian nucleus (CM), and medial pulvinar nucleus (PuM) has emerged as a neuromodulatory intervention for adults with drug-resistant epilepsy (DRE). Despite growing clinical experience, no pooled analysis has integrated outcomes across all three thalamic targets. A PRISMA-compliant systematic search was conducted across PubMed, EMBASE, and Cochrane databases (January 2000-December 2025). Studies reporting seizure frequency reduction following thalamic DBS in ≥4 adults with DRE and ≥6 months of follow-up were included. Pooled descriptive statistics and weighted mean analyses were calculated within each target separately; subgroup comparisons by seizure onset zone and epilepsy classification were performed within each nucleus. Nineteen studies (651 patients) met inclusion criteria: ten ANT (n = 551), seven CM (n = 89), and two PuM (n = 11). Weighted mean seizure frequency reductions were 48.7% (ANT), 71.4% (CM), and 62.0% (PuM). Responder rates (≥50% reduction) were 48.7% (ANT), 76.2% (CM), and 60.0% (PuM). ANT DBS showed progressive improvement from year one (33%-41% reduction) through year five (56%-69% reduction). Temporal lobe origin predicted superior ANT outcomes. CM DBS was most effective for generalized epilepsy syndromes, including Lennox-Gastaut syndrome. PuM DBS yielded promising results for posterior quadrant and temporal-plus epilepsy. Adverse events were target-specific, including depression and memory impairment (ANT), postoperative drowsiness (CM), and hemorrhagic complications (PuM). No stimulation-related mortality occurred. Thalamic DBS provides durable seizure reduction across three nuclear targets, with efficacy varying by epilepsy classification and seizure onset zone. ANT DBS has Class I evidence supporting its use in focal epilepsies, particularly temporal lobe origin. CM DBS shows strong preliminary efficacy for generalized epilepsies, warranting larger randomized trials. PuM DBS requires prospective validation. Head-to-head comparative trials are needed before individualized target selection recommendations can be made.