{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:04:10Z","timestamp":1785420250996,"version":"3.56.0"},"reference-count":78,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Cyprus Institute of Neurology and Genetics"},{"id":[{"id":"https:\/\/ror.org\/01ggsp920","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sci.","Brain Sciences"],"abstract":"<jats:p>Background: Corticospinal plasticity is impaired in MS. In-phase bilateral upper-limb exercises have been shown to improve corticospinal excitability in people with relapsing-remitting multiple sclerosis, but there is limited literature that supports the same conclusion for progressive multiple sclerosis. Therefore, our aim was to investigate whether a 12-week in-phase bilateral upper-limb exercise protocol could enhance corticospinal plasticity and improve clinical outcomes in people with progressive multiple sclerosis. Methods: Five participants (two females; age = 61 \u00b1 12.04 years) with secondary or primary progressive multiple sclerosis were randomized and recruited in a single-case concurrent multiple-baseline design study. The exercise protocol lasted for 12 consecutive weeks (30\u201360 min\/session \u00d7 3 sessions\/week) and incorporated adapted sport-specific activities, functional training and proprioceptive neuromuscular facilitation exercises. To define the functional relationship between the intervention and the results, a visual analysis was conducted. A statistical analysis was performed when a potential sizeable effect was observed. Results: Statistically significant reductions in active motor threshold (primary outcome) were observed in two of the five participants for the left upper limb and in one of the five participants for the right upper limb. Statistically significant improvements were partially observed in muscle strength, pinch strength and cognitive processing speed. Conclusions: Based on the preliminary findings of the current study, in-phase bilateral upper-limb exercises may modulate corticospinal plasticity and improve clinical outcomes in people with progressive multiple sclerosis. However, larger studies are needed to reproduce these results and to establish the effects of in-phase bilateral exercise on both corticospinal plasticity and related clinical outcomes.<\/jats:p>","DOI":"10.3390\/brainsci16080782","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T13:53:26Z","timestamp":1784901206000},"page":"782","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Effects of In-Phase Bilateral Upper-Limb Exercises on Corticospinal Plasticity in People with Progressive Multiple Sclerosis: A Pilot Randomized Single-Case Concurrent Multiple-Baseline Design"],"prefix":"10.3390","volume":"16","author":[{"given":"Marinos","family":"Chatzikonstantinou","sequence":"first","affiliation":[{"name":"Physiotherapy Unit, Neurology Clinics, The Cyprus Institute of Neurology and Genetics, 2371 Nicosia, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7065-1237","authenticated-orcid":false,"given":"Kyriaki","family":"Michailidou","sequence":"additional","affiliation":[{"name":"Biostatistics Department, The Cyprus Institute of Neurology and Genetics, 2371 Nicosia, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2937-384X","authenticated-orcid":false,"given":"Marios","family":"Pantzaris","sequence":"additional","affiliation":[{"name":"Neuroimmunology Department, The Cyprus Institute of Neurology and Genetics, 2371 Nicosia, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavriella","family":"Alexandrou","sequence":"additional","affiliation":[{"name":"Neurophysiology Department, The Cyprus Institute of Neurology and Genetics, 2371 Nicosia, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charalambos C.","family":"Charalambous","sequence":"additional","affiliation":[{"name":"Department of Neurology, School of Medicine, Duke University, Durham, NC 27710, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitris","family":"Sokratous","sequence":"additional","affiliation":[{"name":"Physiotherapy Unit, Neurology Clinics, The Cyprus Institute of Neurology and Genetics, 2371 Nicosia, Cyprus"},{"name":"Department of Life and Health Sciences, Frederick University, 3080 Limassol, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1016\/S0140-6736(08)61620-7","article-title":"Multiple sclerosis","volume":"372","author":"Compston","year":"2008","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"226","DOI":"10.4103\/0972-2327.58276","article-title":"The diagnosis of multiple sclerosis and the clinical subtypes","volume":"12","author":"Hurwitz","year":"2009","journal-title":"Ann. 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