Cognitive safety is a paramount concern when considering deep-brain stimulation (DBS) for drug-resistant epilepsy (DRE), especially for targets like the anterior thalamic nucleus (ANT) involved in memory circuits. A synthesis of long-term cognitive outcomes is needed. This systematic review aimed to evaluate the long-term (≥36 months) cognitive effects of ANT-DBS in patients with DRE. We conducted a systematic search of PubMed/MEDLINE, Embase, Web of Science, and PsycINFO for studies published between January 1, 2015, and December 19, 2025. Eligible studies included adults with DRE who underwent ANT-DBS and reported standardized neuropsychological outcomes at a minimum follow-up of 36 months. Data on cognitive domains (memory, executive function, language, and visuospatial skills) and seizure reduction were extracted. Due to heterogeneity in cognitive measures, findings were synthesized narratively. Three studies met the inclusion criteria, with follow-up durations ranging from 44 months to 7 years. All studies consistently reported no significant long-term cognitive decline at the group level across any assessed domain following ANT-DBS. This cognitive stability was observed alongside substantial and sustained reductions in seizure activity (56.7-73.1% reduction in disabling seizures). The finding is notable given the ANT's role in memory networks and the baseline cognitive vulnerability of the DRE population. This cognitive safety profile, maintained over several years, supports the favorable risk-benefit assessment of this therapy and provides crucial evidence for clinical counseling. Given the limited number of studies, findings should be interpreted as preliminary, though consistent across available evidence.
Sutiono et al. (Sun,) studied this question.