BDNF Val66met Gene Polymorphism in Primary Acute and Subacute Stroke Functional Recovery: A Systematic Review

Background/Objectives: Stroke remains a leading global cause of death and disability, resulting from acute focal injury to the central nervous system. The brain-derived neurotrophic factor (BDNF) gene has been extensively investigated for its involvement in post-stroke neuroplasticity and recovery. This systematic review examines the influence of the BDNF Val66Met (rs6265) variant on functional recovery during the acute and early subacute phases of primary stroke. Methods: The review followed PRISMA guidelines and was registered in PROSPERO (CRD42024549967). Comprehensive literature searches were performed in PubMed, Web of Science, and the Virtual Health Library in December 2024 to identify observational and interventional studies involving adults with acute or subacute primary stroke that evaluated this polymorphism. Results: Of 475 records identified, 11 studies met the inclusion criteria. Sample sizes ranged from 14 to 829 participants, with follow-up intervals ranging from 2 days to 3 months post-stroke. All studies included ischemic stroke, and seven also included hemorrhagic stroke cases. Outcomes assessed were motor recovery, cortical excitability, swallowing, and language function. Overall, most studies reported poorer recovery among Met allele carriers (Val/Met or Met/Met), particularly in motor outcomes. Evidence for cortical excitability and swallowing also suggested unfavorable effects, while language outcomes were inconclusive. Methodological heterogeneity contributed to inconsistent findings. Conclusions: The Met carriers were the most prevalent and frequently associated with poorer post-stroke outcomes, though results varied. These findings underscore the complex interplay between genetics and post-stroke recovery and indicate the need for more robust, standardized research across diverse populations.