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We assessed responsiveness of clinical, electrophysiological and radiological muscle-based assessments to detect MND-related progression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>A prospective, longitudinal cohort study of 29 MND patients and 22 healthy controls was performed. Clinical measures, electrophysiological motor unit number index\/size (MUNIX\/MUSIX) and relative T2- and diffusion-weighted whole-body muscle magnetic resonance (MR) were assessed three times over 12\u00a0months. Multi-variable regression models assessed between-group differences, clinico-electrophysiological associations, and longitudinal changes. Standardized response means (SRMs) assessed sensitivity to change over 12\u00a0months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>MND patients exhibited 18% higher whole-body mean muscle relative T2-signal than controls (95% CI 7\u201329%,<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01), maximal in leg muscles (left tibialis anterior 71% (95% CI 33\u2013122%,<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01). Clinical and electrophysiological associations were evident. By 12\u00a0months, 16 patients had died or could not continue. In the remainder, relative T2-signal increased over 12\u00a0months by 14\u201329% in right tibialis anterior, right quadriceps, bilateral hamstrings and gastrocnemius\/soleus (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01), independent of onset-site, and paralleled progressive weakness and electrophysiological loss of motor units. Highest clinical, electrophysiological and radiological SRMs were found for revised ALS-functional rating scale scores (1.22), tibialis anterior MUNIX (1.59), and relative T2-weighted leg muscle MR (right hamstrings: 0.98), respectively. Diffusion MR detected minimal changes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>MUNIX and relative T2-weighted MR represent objective surrogate markers of progressive denervation in MND. Radiological changes were maximal in leg muscles, irrespective of clinical onset-site.<\/jats:p><\/jats:sec>","DOI":"10.1007\/s00415-019-09580-x","type":"journal-article","created":{"date-parts":[[2019,10,17]],"date-time":"2019-10-17T21:18:06Z","timestamp":1571347086000},"page":"244-256","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Longitudinal multi-modal muscle-based biomarker assessment in motor neuron disease"],"prefix":"10.1007","volume":"267","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0342-7184","authenticated-orcid":false,"given":"Thomas M.","family":"Jenkins","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James J. 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The numbers\u00a0in the Table\u00a05 appear to have been reproduced wrongly as dates, rather than percentages.","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"We have no conflicts of interest in regard to this study. This study was supported by the NIHR Sheffield Biomedical Research Centre and by charitable funding from the British Medical Association (Vera Down grant R\/140137-11-1) and Neurocare\/Ryder Briggs Trust (R\/136623-11-1). TJ and JJPA were supported by National Institute for Health Research (NIHR) Clinical Lectureships during the conduct of this study. PJS is supported as an NIHR Senior Investigator and by grants from NIHR, the Medical Research Council, the Motor Neuron Disease Association and EU Horizon 2020. The funders had no role in the conduct of the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and\/or national research committee (Yorkshire and the Humber Research Ethics Committee (13\/YH\/0273)) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical standards"}},{"value":"Written informed consent was obtained.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}