{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:08:49Z","timestamp":1753891729944,"version":"3.41.2"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T00:00:00Z","timestamp":1692921600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>The incidence of stroke is increasing steadily due to factors such as population aging. Approximately 80% of stroke survivors have motor disorders affecting their daily lives. Repetitive transcranial magnetic stimulation (rTMS) has been reported to maximize functional recovery after stroke along with exercise intervention in upper limb rehabilitation treatment. However, whether rTMS affects the recovery of upper limb function in patients with stroke remains unclear. Therefore, in this trial, we will investigate the efficacy of low-frequency rTMS in patients with subcortical and brainstem ischemic stroke.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study has been designed as a multi-center, double-blind, randomized controlled trial to compare the efficacy of low-frequency rTMS over the contralesional M1 with sham stimulation. Overall, 88 participants will be allocated to the intervention or control group in a 1:1 ratio, with stratification according to their initial upper extremity Fugl-Meyer assessment (UE-FMA) score. The participants will receive either 30\u2009min of real rTMS (intervention group) or sham rTMS (control group), followed by 30\u2009min of occupational therapy for 10 consecutive workdays. All the participants will receive the same amount of rehabilitation therapy throughout the intervention period. Evaluations will be performed at baseline (T0), at the end of treatment (T1), and 4\u2009weeks after the end of treatment (T2), including the box and block test (BBT), UE-FMA, Korean version of the Modified Barthel Index, and NIH Stroke Scale scores, Finger tapping test, Brunnstrom stage, modified Ashworth scale, and grip strength. The primary outcome will be the change in the BBT score between T0 and T2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study will provide evidence on the efficacy of low-frequency rTMS in motor function recovery of the upper limb in patients with subacute, subcortical, and brainstem ischemic stroke.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical trial registration<\/jats:title><jats:p><jats:ext-link>ClinicalTrials.gov<\/jats:ext-link>, identifier [NCT05535504].<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2023.1216510","type":"journal-article","created":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T13:04:20Z","timestamp":1692968660000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Investigation of the efficacy of low-frequency repetitive transcranial magnetic stimulation on upper-limb motor recovery in subacute ischemic stroke without cortical involvement: a protocol paper for a multi-center, double-blind randomized controlled trial"],"prefix":"10.3389","volume":"14","author":[{"given":"Hee-Mun","family":"Cho","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seungwoo","family":"Cha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min Kyun","family":"Sohn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sungju","family":"Jee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Won Kee","family":"Chang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Won-Seok","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nam-Jong","family":"Paik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,8,25]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2982","DOI":"10.1016\/j.jacc.2020.11.010","article-title":"Global burden of cardiovascular diseases and risk factors, 1990-2019: update from the Gbd 2019 study","volume":"76","author":"Roth","year":"2020","journal-title":"J Am Coll Cardiol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1177\/1545968310364058","article-title":"Functional neuroimaging studies of early upper limb recovery after stroke: a systematic review of the literature","volume":"24","author":"Buma","year":"2010","journal-title":"Neurorehabil Neural Repair"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"175","DOI":"10.31661\/jbpe.v0i0.879","article-title":"The effect of high-frequency repetitive transcranial magnetic stimulation on functional indices of affected upper limb in patients with subacute stroke","volume":"11","author":"Moslemi Haghighi","year":"2021","journal-title":"J Biomed Phys"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.jns.2016.08.016","article-title":"Transcranial magnetic stimulation combined with upper-limb training for improving function after stroke: a systematic review and meta-analysis","volume":"369","author":"Graef","year":"2016","journal-title":"J Neurol Sci"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2013\/539146","article-title":"Combining Rtms and task-oriented training in the rehabilitation of the arm after stroke: a pilot randomized controlled trial","volume":"2013","author":"Higgins","year":"2013","journal-title":"Stroke Res Treat"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"179","DOI":"10.3233\/RNN-2012-110162","article-title":"Rtms with motor training modulates Cortico-basal ganglia-thalamocortical circuits in stroke patients","volume":"30","author":"Chang","year":"2012","journal-title":"Restor Neurol Neurosci"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/j.neulet.2013.08.013","article-title":"Inhibitory theta burst stimulation of affected hemisphere in chronic stroke: a proof of principle. 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