Combined high-frequency rTMS and rPMS for upper limb motor recovery in subacute stroke: A randomized sham-controlled trial

Background Impaired upper limb motor function remains a significant and enduring clinical challenge in the post-stroke recovery phase. The combination of repetitive transcranial magnetic stimulation (rTMS) and repetitive peripheral magnetic stimulation (rPMS) may improve recovery via complementary central-peripheral modulation. However, its clinical efficacy remains to be fully elucidated. This study investigated the effects of sequential dual-modality stimulation (rPMS followed by high frequency (HF)-rTMS) on improving upper limb motor function and basic activities of daily living in individuals during the subacute phase of stroke. Methods In this three-arm, randomized, sham-controlled, evaluator-blinded trial, 60 patients with subacute stroke with upper limb motor deficits were randomly assigned to: Combined HF-rTMS and rPMS (Combined Group, n = 20), rTMS alone (Central Group, n = 20), or sham stimulation (Control Group, n = 20). All participants received 10 sessions of neuromodulation (5 days/week for 2 weeks) in addition to conventional rehabilitation. The primary endpoint was the Fugl–Meyer Assessment of Upper Extremity (FMA-UE) score, while the secondary endpoints were the Action Research Arm Test (ARAT) performance and Barthel Index (BI) score for functional independence. Analysis of covariance was used to account for baseline differences and to assess the efficacy of the intervention at the post-treatment time point. Results The Combined Group demonstrated superior motor recovery, achieving significantly higher adjusted mean FMA-UE scores than the Control Group (Bonferroni-adjusted p = 0.028). The subscale analysis revealed that these gains were primarily driven by improvements in distal motor function ( F = 5.236, p = 0.008), with the Combined Group significantly outperforming the Control Group (Bonferroni-adjusted p = 0.007). Regarding secondary outcomes, the between-group analysis did not reveal any statistically significant differences in manual dexterity (measured by the ARAT; p = 0.207) or activities of daily living (assessed by the BI; p = 0.072; not significant after Bonferroni correction). Conclusions Combined HF-rTMS and rPMS represent a promising therapeutic approach to improve upper limb motor recovery during the subacute phase of stroke, with therapeutic benefits predominantly localized to the distal motor domain. These findings support the clinical value of integrating central and peripheral neuromodulation strategies to optimize functional independence following stroke.