Front Neurol. 2026 Jun 1;17:1840684. doi: 10.3389/fneur.2026.1840684. eCollection 2026.
ABSTRACT
BACKGROUND: Gait disorder and cognitive dysfunction are the most common symptoms in patients with cerebral small vessel disease (CSVD), significantly impacting patients’ quality of life. Currently, there remains a lack of effective treatment for gait disorder and cognitive dysfunction of CSVD. In this randomized, single-blind, sham-controlled study, we conducted high-dose accelerated intermittent theta burst stimulation (aiTBS) in 36 patients with CSVD to investigate the efficacy and safety of high-dose aiTBS targeting the primary motor cortex (M1 area) for treating various symptoms of CSVD, particularly gait and cognitive function.
METHODS: The patients were randomly assigned to two groups of real (n = 19) or sham (n = 17) aiTBS targeting the primary motor cortex. Both groups received 14 consecutive sessions of real-aiTBS or sham-aiTBS. Primary outcome was the change of 3-meter Timed Up and Go (3mTUG) duration, assessed at baseline (T0) and immediately post-intervention (T1), with follow-up evaluations at 4 weeks after intervention (T2). Secondary outcomes included changes in the Tinetti Performance-Oriented Mobility Assessment (Tinetti) score, the Chinese version of the Mini-Mental State Examination (CMMS) score, the Montreal Cognitive Assessment (MoCA) score, three-dimensional gait analysis, and multidimensional function scale scores after intervention.
RESULTS: Compared to the sham-aiTBS group, the real-aiTBS group exhibited significantly greater improvements in multidimensional gait, cognitive, affective and autonomic nervous function assessments. At the 4-week follow-up, time effects were statistically significant for the 3mTUG duration, Tinetti, CMMS, and MoCA scores. The real-aiTBS group exhibited more pronounced group-by-time interaction effects for the 3mTUG duration, Tinetti, and CMMS scores, while no statistically significant differences from the sham-aiTBS group were observed for the MoCA score. The aiTBS intervention response is correlated to the CSVD neuroimaging features, including periventricular white matter hyperintensity, enlarged perivascular space, cortical atrophy, lacune and total CSVD burden score.
CONCLUSION: The aiTBS holds promise as a valuable therapeutic approach for CSVD. High-dose aiTBS targeting the M1 area improved clinical symptoms such as gait and cognitive disorder in patients with CSVD. The therapeutic response to aiTBS in CSVD patients is related to the CSVD neuroimaging phenotypes.
PMID:42306624 | PMC:PMC13265494 | DOI:10.3389/fneur.2026.1840684