Continuous Theta-Burst Stimulation of the Contralesional Primary Motor Cortex for Promotion of Upper Limb Recovery After Stroke: A Randomized Controlled Trial.

Background: Despite improvements in acute stroke therapies and rehabilitation strategies, many stroke patients are left with long-term upper limb motor impairment. We assessed whether an inhibitory repetitive transcranial magnetic stimulation treatment paradigm started within 3 weeks after stroke onset promotes upper limb motor recovery.
Methods: We performed a single-center randomized, sham-controlled clinical trial. Patients with ischemic stroke or intracerebral hemorrhage and unilateral upper limb motor impairment were randomized to 10 daily sessions of active or sham continuous theta-burst stimulation (cTBS) of the contralesional primary motor cortex combined with standard upper limb therapy, started within 3 weeks after stroke onset. The primary outcome was the change in the Action Research Arm Test score from baseline (pretreatment) at 3 months after stroke. Secondary outcomes included the score on the modified Rankin Scale at 3 months and the length of stay at the rehabilitation center. Statistical analyses were performed using mixed models for repeated measures.
Results: We enrolled 60 patients between April 2017 and February 2021, of whom 29 were randomized to active cTBS and 31 to sham cTBS. One patient randomized to active cTBS withdrew consent before the intervention and was excluded from the analyses. The mean difference in the change in Action Research Arm Test score from baseline at 3 months poststroke was 9.6 points ([95% CI, 1.2-17.9]; P =0.0244) in favor of active cTBS. Active cTBS was associated with better scores on the modified Rankin Scale at 3 months (OR, 0.2 [95% CI, 0.1-0.8]; P =0.0225) and with an 18 days shorter length of stay at the rehabilitation center than sham cTBS ([95% CI, 0.0-36.4]; P =0.0494). There were no serious adverse events.
Conclusions: Ten daily sessions of cTBS of the contralesional primary motor cortex combined with upper limb training, started within 3 weeks after stroke onset, promote recovery of the upper limb, reduce disability and dependence and leads to earlier discharge from the rehabilitation center.
Registration: URL: https://trialsearch.who.int/; Unique identifier: NTR6133.
Competing Interests: Disclosures J.J.T. Vink is a part-time employee of and Dr Neggers is the CEO and shareholder of Brain Science Tools B.V. Data analysis was performed during J.J.T. Vink’s part-time employment at Brain Science Tools B.V. Dr van der Worp is consultant for Bayer and receives funding from the Dutch Heart Foundation, Horizon 2020 Framework Programme and Stryker. The other authors report no conflicts.