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SBMA Functional Rating Scale (\n                      <jats:italic>SBMAFRS<\/jats:italic>\n                      ), its subscale (mSBMAFRS), and Six-Minute Walk Test (\n                      <jats:italic>6MWT<\/jats:italic>\n                      ) are commonly used trial endpoints, but thresholds for clinically meaningful change remain undefined. Minimal clinically important difference (\n                      <jats:italic>MCID<\/jats:italic>\n                      ) estimates are needed to interpret longitudinal outcomes and inform trial design.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We retrospectively analysed ambulatory, genetically confirmed SBMA patients. Eighty consecutive visit pairs from 44 patients included concurrent Global Rating of Change (\n                      <jats:italic>GRC<\/jats:italic>\n                      ) assessments, and 47 visit pairs from 30 patients included concurrent 6MWT data. At follow-up, patients rated overall change since the previous visit on a 3\u2011level GRC (unchanged, slightly worse, much worse). Anchor-based MCIDs for worsening were derived from differences in change scores between GRC categories and compared with distribution-based estimates (0.5 baseline standard deviation). Sensitivity analyses and Monte Carlo resampling assessed robustness.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Anchor\u2011based MCID estimates for worsening were \u22121.13 and \u22121.46 points for the SBMAFRS total score, \u22120.53 and \u22121.09 points for the mSBMAFRS, and \u221234.5 and \u221232.4\u00a0m for the 6MWT. The mSBMAFRS showed the most consistent gradient across GRC categories and remained significant in sensitivity analyses. Distribution\u2011based MCIDs (2.30, 1.42 points and 61.85\u00a0m, respectively) were consistently larger than anchor\u2011based values. Age, disease duration, and CAG repeat length did not predict perceived worsening.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These data provide the first patient\u2011anchored MCID estimates for SBMA outcome measures, support use of the mSBMAFRS, and offer thresholds for responder definitions and sample-size calculations in future SBMA trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00415-026-14032-4","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T17:30:42Z","timestamp":1785519042000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Estimating the minimal clinically important difference of functional outcomes in spinal and bulbar muscular atrophy"],"prefix":"10.1007","volume":"273","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3343-1547","authenticated-orcid":false,"given":"Matteo","family":"Zanovello","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Sabbatini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Paredi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Romito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Andreetta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Blasi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Musso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Poletti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosario","family":"Vasta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Basso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaele","family":"Dubbioso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Pennuto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo Maria","family":"Minicuci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Pegoraro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Bello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianni","family":"Sorar\u00f9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"issue":"6330","key":"14032_CR1","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1038\/352077a0","volume":"352","author":"AR La Spada","year":"1991","unstructured":"La Spada AR, Wilson EM, Lubahn DB, Harding AE, Fischbeck KH (1991) Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. 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Written informed consent was obtained from every patient prior to study inclusion.","order":2,"name":"Ethics","label":"Ethical approval statement","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"497"}}