BDNF Val66Met polymorphism modulates early TMS-EEG plasticity and rTMS efficacy in patients with anterior circulation...

This study aimed to explore whether the BDNF Val66Met polymorphism influences early cortical plasticity, as measured by TMS-EEG, and its impact on rTMS therapy response in anterior-circulation ischemic stroke, with outcomes evaluated at day 14 and day 90 post-stroke.

We retrospectively analyzed 200 patients genotyped for BDNF Val66Met: Val/Val (n = 102), Val/Met (n = 79), and Met/Met (n = 19). Demographic and clinical data were collected, and each patient underwent TMS-EEG before rTMS. Neurological status (NIHSS and mRS) was assessed at day 14 and day 90 post-stroke. Plasticity was measured using the composite plasticity index, N100, P30, SICI, and ICF. Clinical endpoints included NIHSS change, responder rate, and mRS distribution.

Baseline profiles were comparable across groups. The genotype distribution was consistent with Hardy-Weinberg equilibrium and comparable to that of the general population. Val/Val carriers showed the most pronounced plasticity (plasticity index: 0.22 ± 0.06 vs. 0.12 ± 0.06 vs. 0.07 ± 0.06; p < 0.001). Clinically, Val/Val patients showed greater NIHSS improvement at both day 14 (ΔNIHSS: 7.4 vs. 5.3 vs. 4.9) and day 90 (8.2 vs. 6.0 vs. 5.1; p < 0.001). Responder rates were highest in Val/Val (p = 0.0045 at day 14, p = 0.0235 at day 90), with better mRS distribution (p < 0.001). The plasticity index positively correlated with ΔNIHSS (r = 0.58 at day 14; r = 0.61 at day 90; both p < 0.001) and negatively with mRS (r=-0.52; p < 0.001).

The BDNF Val66Met polymorphism significantly modulates cortical excitability and functional recovery following stroke. Our findings indicate that TMS-EEG plasticity mediates the relationship between genotype and rTMS efficacy, supporting its potential as a biomarker for personalized rehabilitation strategies.