Abstract
BACKGROUND: Post-stroke dysphagia (PSD) is a common and serious complication, yet conventional rehabilitation therapies have limited efficacy. Repetitive transcranial magnetic stimulation (rTMS) is a promising treatment, but its optimal intervention strategy remains undetermined. METHODS: Seventy-five PSD patients were randomly assigned in a 1:1:1 ratio to the sham rTMS group, affected rTMS group and bilateral rTMS group. All groups received the corresponding rTMS intervention and conventional rehabilitation therapy. Swallowing function was assessed at baseline (T0) and after treatment (T1) using the standardized swallowing assessment (SSA), penetration-aspiration scale (PAS), yale pharyngeal residue severity rating scale (YPR-SRS), and suprahyoid motor evoked potentials (MEP). Adverse reactions and dropouts were recorded. RESULTS: After treatment, the SSA scores of all three groups were significantly improved. Bilateral rTMS showed significantly greater improvement in SSA and a higher treatment response rate (77.27%) compared to both the sham group and the affected rTMS group (p < 0.001). Mixed-effects model and intention-to-treat analyses both supported the optimal efficacy of bilateral rTMS (interaction effect p < 0.01). Regarding swallowing safety (PAS), the bilateral rTMS group's score was significantly lower than that of the sham group (p = 0.017). In terms of pharyngeal residue clearance (YPR-SRS), the bilateral rTMS group showed significantly greater improvement in the piriform sinuses compared to the other two groups, and superior improvement in the vallecula compared to the sham group (p < 0.05). After treatment, MEP amplitudes increased in all groups. Notably, only the bilateral rTMS group not only significantly increased MEP amplitudes on both sides (p < 0.01) but also significantly shortened the latency on the contralesional side (p = 0.046). The bilateral rTMS group achieved a "large effect size" in improving SSA scores, increasing MEP amplitudes, and shortening latency on the contralesional side, with the SSA effect size (D = 2.339) far exceeding that of the other groups. All treatment regimens were well-tolerated, with only 5 cases of transient scalp discomfort reported and no serious adverse events. CONCLUSIONS: Conventional rehabilitation combined with 10 Hz rTMS targeting the swallowing cortex can effectively improve swallowing function in PSD patients. Bilateral rTMS is a superior strategy. Its therapeutic advantage may stem from the synergistic modulation of bilateral cortical excitability and neural conduction efficiency, providing a better multi-target neuromodulation option for clinical practice. CLINICAL TRIAL REGISTRATION: No: ChiCTR2300068730. https://www.chictr.org.cn/showproj.html?proj=182568.