{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T00:00:07Z","timestamp":1774742407360,"version":"3.50.1"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T00:00:00Z","timestamp":1649376000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T00:00:00Z","timestamp":1649376000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Digit. Med."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Amyotrophic Lateral Sclerosis (ALS) disease severity is usually measured using the subjective, questionnaire-based revised ALS Functional Rating Scale (ALSFRS-R). Objective measures of disease severity would be powerful tools for evaluating real-world drug effectiveness, efficacy in clinical trials, and for identifying participants for cohort studies. We developed a machine learning (ML) based objective measure for ALS disease severity based on voice samples and accelerometer measurements from a four-year longitudinal dataset. 584 people living with ALS consented and carried out prescribed speaking and limb-based tasks. 542 participants contributed 5814 voice recordings, and 350 contributed 13,009 accelerometer samples, while simultaneously measuring ALSFRS-R scores. Using these data, we trained ML models to predict bulbar-related and limb-related ALSFRS-R scores. On the test set (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009109 participants) the voice models achieved a multiclass AUC of 0.86 (95% CI, 0.85\u20130.88) on speech ALSFRS-R prediction, whereas the accelerometer models achieved a median multiclass AUC of 0.73 on 6 limb-related functions. The correlations across functions observed in self-reported ALSFRS-R scores were preserved in ML-derived scores. We used these models and self-reported ALSFRS-R scores to evaluate the real-world effects of edaravone, a drug approved for use in ALS. In the cohort of 54 test participants who received edaravone as part of their usual care, the ML-derived scores were consistent with the self-reported ALSFRS-R scores. At the individual level, the continuous ML-derived score can capture gradual changes that are absent in the integer ALSFRS-R scores. This demonstrates the value of these tools for assessing disease severity and, potentially, drug effects.\n                  <\/jats:p>","DOI":"10.1038\/s41746-022-00588-8","type":"journal-article","created":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T06:11:21Z","timestamp":1649398281000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["A machine-learning based objective measure for ALS disease severity"],"prefix":"10.1038","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2996-6418","authenticated-orcid":false,"given":"Fernando G.","family":"Vieira","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3729-8456","authenticated-orcid":false,"given":"Subhashini","family":"Venugopalan","sequence":"additional","affiliation":[]},{"given":"Alan S.","family":"Premasiri","sequence":"additional","affiliation":[]},{"given":"Maeve","family":"McNally","sequence":"additional","affiliation":[]},{"given":"Aren","family":"Jansen","sequence":"additional","affiliation":[]},{"given":"Kevin","family":"McCloskey","sequence":"additional","affiliation":[]},{"given":"Michael P.","family":"Brenner","sequence":"additional","affiliation":[]},{"given":"Steven","family":"Perrin","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2022,4,8]]},"reference":[{"key":"588_CR1","unstructured":"Jean-Martin, C. Amyotrophies spinales deuteropathiques scl\u00e9rose lat\u00e9rale amyotrophique Scl\u00e9rose lat\u00e9rale amyotrophique. (Bureaux du progr\u00e8s m\u00e9dical, 1874)."},{"key":"588_CR2","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1093\/brain\/109.5.939","volume":"109","author":"M Swash","year":"1986","unstructured":"Swash, M., Leader, M., Brown, A. & Swettenham, K. W. Focal loss of anterior horn cells in the cervical cord in motor neuron disease. Brain 109, 939\u2013952 (1986).","journal-title":"Brain"},{"key":"588_CR3","doi-asserted-by":"publisher","first-page":"1571","DOI":"10.1212\/01.wnl.0000260965.20021.47","volume":"68","author":"J Ravits","year":"2007","unstructured":"Ravits, J., Paul, P. & Jorg, C. Focality of upper and lower motor neuron degeneration at the clinical onset of ALS. 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S.P. is an employee of Eledon Pharmaceuticals which aims to develop and market pharmaceuticals for ALS and other disease indications. The remaining authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"45"}}