{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T14:02:56Z","timestamp":1781186576292,"version":"3.54.1"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"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>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Long-term clinical trajectories and accessible biomarkers in adult spinal muscular atrophy (SMA) remain insufficiently characterized under real-world treatment conditions. We conducted a single-center longitudinal study to evaluate motor function, genotype\u2013phenotype relationships, and clinically accessible biomarkers in treated adults with SMA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Twenty-three Japanese adults with genetically confirmed 5q-SMA treated with nusinersen or risdiplam (2018\u20132025) underwent repeated assessments of Revised Upper Limb Module (RULM), Hammersmith Functional Motor Scale Expanded (HFMSE), and laboratory, physiological, and electrophysiological measures. Associations were explored using correlation analyses, linear mixed-effects models, and exploratory machine-learning approaches.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Higher\n                      <jats:italic>SMN2<\/jats:italic>\n                      copy number was associated with later onset and milder severity. Hybrid\n                      <jats:italic>SMN<\/jats:italic>\n                      alleles showed heterogeneous patterns depending on copy-number context. Longitudinally (mean follow-up 57\u202fmonths), motor scores often improved or stabilized during the first year after treatment initiation, followed by plateau or gradual decline in some patients. In mixed-effects models, vital capacity (%VC) was independently associated with RULM, while other biomarkers showed consistent associations with motor scores. Exploratory machine-learning suggested that ulnar compound muscle action potential (CMAP) amplitude and creatine kinase (CK) contributed to model predictions, although baseline features did not reliably predict short-term motor changes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In treated adults with SMA, simple clinical measures such as %VC, CK, ulnar CMAP amplitude are associated with motor status and may support routine monitoring, while prediction of treatment responsiveness remains challenging.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1870339","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T13:37:12Z","timestamp":1781185032000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Longitudinal motor function and biomarker correlates in treated adult spinal muscular atrophy: a single-center cohort study"],"prefix":"10.3389","volume":"17","author":[{"given":"Chikashi","family":"Yano","sequence":"first","affiliation":[{"name":"Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences","place":["Kagoshima, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Ando","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences","place":["Kagoshima, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Yoshimura","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences","place":["Kagoshima, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujiro","family":"Higuchi","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences","place":["Kagoshima, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshikatsu","family":"Noda","sequence":"additional","affiliation":[{"name":"Division of Neurology, Kobe University Graduate School of Medicine","place":["Kobe, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Hui","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences","place":["Kagoshima, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomonori","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences","place":["Kagoshima, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Hobara","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences","place":["Kagoshima, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Risa","family":"Nagatomo","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences","place":["Kagoshima, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumikazu","family":"Kojima","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences","place":["Kagoshima, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mika","family":"Yuji","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences","place":["Kagoshima, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Hiramatsu","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences","place":["Kagoshima, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Nozuma","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences","place":["Kagoshima, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Hashiguchi","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences","place":["Kagoshima, Japan"]},{"name":"Department of Neurology, National Hospital Organization Okinawa Hospital","place":["Okinawa, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Sakiyama","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences","place":["Kagoshima, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Takashima","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences","place":["Kagoshima, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,11]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1002\/mus.21350","article-title":"An analysis of disease severity based on SMN2 copy number in adults with spinal muscular atrophy","volume":"40","author":"Elsheikh","year":"2009","journal-title":"Muscle Nerve"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1016\/j.nmd.2007.02.006","article-title":"The hammersmith functional score correlates with the SMN2 copy number: a multicentric study","volume":"17","author":"Tiziano","year":"2007","journal-title":"Neuromuscul Disord"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/S1474-4422(21)00367-7","article-title":"Safety and efficacy of once-daily risdiplam in type 2 and non-ambulant type 3 spinal muscular atrophy (SUNFISH part 2): a phase 3, double-blind, randomised, 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