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Neuromuscular ultrasound (NMUS) provides a non-invasive means to visualize peripheral nerve and muscle integrity, but its potential to delineate ALS subtypes has not been systematically explored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To identify clinically meaningful ALS subgroups through unsupervised clustering of NMUS features integrated with clinical and electrophysiological data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A total of 454 ALS patients (August 2024\u2013December 2025) underwent standardized NMUS assessment, including muscle thickness, echogenicity, and nerve cross-sectional area, alongside ALSFRS-R, manual muscle testing (MMT), and compound muscle action potentials (CMAPs). K-means clustering was applied to standardized NMUS variables, with cluster stability assessed using silhouette coefficients, sensitivity analyses (\n                      <jats:italic>k<\/jats:italic>\n                      \u2009=\u20092\u20135), and resampling-based adjusted Rand indices. Multivariable regression examined associations between cluster membership and ALSFRS-R.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Two reproducible NMUS-based subgroups were identified: a Mild cluster (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009288, 63.4%) and a Severe cluster (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009166, 36.6%). The Severe cluster showed reduced muscle thickness and higher echogenicity across multiple sites, together with lower ALSFRS-R scores (adjusted\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u2009\u2212\u20093.84, 95% CI\u2009\u2212\u20095.41 to\u2009\u2212\u20092.27,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001). Cluster membership correlated negatively with MMT and CMAP amplitudes, supporting functional and electrophysiologic validity. Stability metrics confirmed robustness of the two-cluster solution.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Integrating NMUS with clinical data enables objective, imaging-derived stratification of ALS patients into biologically and functionally distinct subgroups. This approach offers a pragmatic framework for phenotypic characterization and may inform personalized monitoring and trial design in ALS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00415-026-13705-4","type":"journal-article","created":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T16:34:35Z","timestamp":1771691675000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Imaging-derived neuromuscular ultrasound phenotypes are associated with functional status in amyotrophic lateral sclerosis"],"prefix":"10.1007","volume":"273","author":[{"given":"Ying","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianhua","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jialei","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyi","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junlin","family":"Ding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuxuan","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0759-3684","authenticated-orcid":false,"given":"Gaoyi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,2,21]]},"reference":[{"issue":"10360","key":"13705_CR1","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1016\/S0140-6736(22)01272-7","volume":"400","author":"EL Feldman","year":"2022","unstructured":"Feldman EL et al (2022) Amyotrophic lateral sclerosis. 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