Excitatory Repetitive Transcranial Magnetic Stimulation Over the Ipsilesional Hemisphere for Upper Limb Motor Function After Stroke: A Systematic Review and Meta-Analysis

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a promising therapy to promote recovery of the upper limb after stroke. According to the regulation of cortical excitability, rTMS can be divided into excitatory rTMS and inhibitory rTMS, and excitatory rTMS includes high-frequency rTMS (HF-rTMS) or intermittent theta-burst stimulation (iTBS). We aimed to evaluate the effects of excitatory rTMS over the ipsilesional hemisphere on upper limb motor recovery after stroke. METHODS: Databases of PubMed, Embase, ISI Web of Science, and the Cochrane Library were searched for randomized controlled trials published before 31 December 2021. RCTs on the effects of HF-rTMS or iTBS on upper limb function in patients diagnosed with stroke were included. Two researchers independently screened the literature, extracted the data, and assessed quality. The meta-analysis was performed by using Review Manager Version 5.4 software. RESULTS: Fifteen studies with 449 participants were included in this meta-analysis. This meta-analysis found that excitatory rTMS had significant efficacy on upper limb motor function (MD = 5.88, 95% CI, 3.32–8.43, P < 0.001), hand strength (SMD = 0.53, 95% CI, 0.04–1.01, P = 0.03), and hand dexterity (SMD = 0.76, 95% CI, 0.39–1.14, P < 0.001). Subgroup analyses based on different types of rTMS showed that both iTBS and HF-rTMS significantly promoted upper limb motor function (iTBS, P < 0.001; HF-rTMS, P < 0.001) and hand dexterity (iTBS, P = 0.01; HF-rTMS, P < 0.001) but not hand strength (iTBS, P = 0.07; HF-rTMS, P = 0.12). Further subgroup analysis based on the duration of illness demonstrated that applying excitatory rTMS during the first 3 months (<1 month, P = 0.01; 1–3 months, P = 0.001) after stroke brought significant improvement in upper limb motor function but not in the patients with a duration longer than 3 months (P = 0.06). We found that HF-rTMS significantly enhanced the motor evoked potential (MEP) amplitude of affected hemisphere (SMD = 0.82, 95% CI, 0.32–1.33, P = 0.001). CONCLUSION: Our study demonstrated that excitatory rTMS over the ipsilesional hemisphere could significantly improve upper limb motor function, hand strength, and hand dexterity in patients diagnosed with stroke. Both iTBS and HF-rTMS which could significantly promote upper limb motor function and hand dexterity, and excitatory rTMS were beneficial to upper limb motor function recovery only when applied in the first 3 months after stroke. HF-rTMS could significantly enhance the MEP amplitude of the affected hemisphere. High-quality and large-scale randomized controlled trials in the future are required to confirm our conclusions. CLINICAL TRIAL REGISTRATION: www.crd.york.ac.uk/prospero/, identifier: CRD42022312288.