{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T03:34:47Z","timestamp":1791862487852,"version":"4.3.4"},"reference-count":35,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of University and Research","award":["# PNC0000007"],"award-info":[{"award-number":["# PNC0000007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>(1) Background: Post-stroke spasticity limits motor recovery and independence. Combining botulinum toxin type-A (BoNT-A) injection with intensive, task-specific robot-assisted therapy (RAT) might enhance neuroplasticity and functional gains, but its additive effect and optimal timing are uncertain. (2) Methods: We systematically searched major medical databases and trial registries up to April 2025 for randomized controlled trials in adults with post-stroke spasticity comparing botulinum toxin type-A injection plus RAT with toxin injection plus conventional therapy, or RAT alone with RAT combined with toxin injection. Risk of bias was assessed using the RoB 2 tool, and findings were synthesized narratively. (3) Results: Seven trials (n = 229) were included. Across all studies, toxin treatment reduced spasticity within groups, whereas additional spasticity reduction with RAT versus conventional rehabilitation was inconsistent. In contrast, several lower-limb trials reported greater improvements in walking capacity and balance when RAT was added, while upper-limb trials showed comparable motor recovery across treatment arms with occasional advantages in strength and movement quality. A pilot four-arm study suggested that starting RAT around four weeks after injection may maximize upper-limb motor gains. (4) Conclusions: The combination of BoNT-A with RAT appears safe and is particularly promising for gait rehabilitation, but further research is needed to define optimal timing and protocols.<\/jats:p>","DOI":"10.3390\/toxins17120569","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T10:46:18Z","timestamp":1764067578000},"page":"569","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Botulinum Toxin Combined with Robot-Assisted Therapy for Post-Stroke Spasticity: A Systematic Review"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6748-9152","authenticated-orcid":false,"given":"Salvatore","family":"Facciorusso","sequence":"first","affiliation":[{"name":"Spasticity and Movement Disorders \u201cReSTaRt\u201d Unit, Physical Medicine and Rehabilitation Section, Azienda Ospedaliero-Universitaria Ospedali Riuniti Di Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Spina","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Science, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5930-5974","authenticated-orcid":false,"given":"Mirko","family":"Filippetti","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37129 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajiv","family":"Reebye","sequence":"additional","affiliation":[{"name":"Division of Physical Medicine and Rehabilitation, Faculty of Medicine, University of British Columbia, Vancouver, BC V5Z 2G9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5681-1916","authenticated-orcid":false,"given":"Gerard E.","family":"Francisco","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine & Rehabilitation, University of Texas Health McGovern Medical School, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1452-8485","authenticated-orcid":false,"given":"Andrea","family":"Santamato","sequence":"additional","affiliation":[{"name":"Spasticity and Movement Disorders \u201cReSTaRt\u201d Unit, Physical Medicine and Rehabilitation Section, Azienda Ospedaliero-Universitaria Ospedali Riuniti Di Foggia, 71122 Foggia, Italy"},{"name":"Department of Medical and Surgical Science, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1177\/17474930241308142","article-title":"World Stroke Organization: Global Stroke Fact Sheet 2025","volume":"20","author":"Feigin","year":"2025","journal-title":"Int. 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