Genetic polymorphisms and post-stroke upper limb motor improvement – A systematic review and meta-analysis

Abstract

Background: Post-stroke upper limb (UL) motor improvement is associated with adaptive neuroplasticity and motor learning. Both intervention-related (including provision of intensive, variable, and task-specific practice) and individual-specific factors (including the presence of genetic polymorphisms) influence improvement. In individuals with stroke, most commonly, polymorphisms are found in Brain Derived Neurotrophic Factor (BDNF), Apolipoprotein (APOE) and Catechol-O-Methyltransferase (COMT). These involve a replacement of cystine by arginine (APOEε4) or valines by 1 or 2 methionines (BDNF:val66met, met66met; COMT:val158met; met158met). However, the implications of these polymorphisms on post-stroke UL motor improvement specifically have not yet been elucidated. Objective: Examine the influence of genetic polymorphism on post-stroke UL motor improvement. Design: Systematic Review and Meta-Analysis. Methods: We conducted a systematic search of the literature published in English language. The modified Downs and Black checklist helped assess study quality. We compared change in UL motor impairment and activity scores between individuals with and without the polymorphisms. Meta-analyses helped assess change in motor impairment (Fugl Meyer Assessment) scores based upon a minimum of 2 studies/time point. Effect sizes (ES) were quantified based upon the Rehabilitation Treatment Specification System as follows: small (0.08-0.18), medium (0.19 -0.40) and large (≥0.41). Results: We retrieved 10 (4 good and 6 fair quality) studies. Compared to those with BDNF val66met and met66met polymorphism, meta-analyses revealed lower motor impairment (large ES) in those without the polymorphism at intervention completion (0.5, 95% CI: 0.11-0.88) and at retention (0.58, 95% CI:0.06-1.11). The presence of CoMT val158met or met158met polymorphism had similar results, with lower impairment (large ES ≥1.5) and higher activity scores (large ES ranging from 0.5-0.76) in those without the polymorphism. Presence of APOEε4 form did not influence UL motor improvement. Conclusion: Polymorphisms with the presence of 1 or 2 met alleles in BDNF and COMT negatively influence UL motor improvement. Registration: https://osf.io/wk9cf/.