{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:13:54Z","timestamp":1789985634282,"version":"4.0.1"},"reference-count":28,"publisher":"BMJ","issue":"11","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Neurol Neurosurg Psychiatry"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>The choice of adequate proxy for long-term survival, the ultimate outcome in randomised clinical trials (RCT) assessing disease-modifying treatments for amyotrophic lateral sclerosis (ALS), is a key issue. The intrinsic limitations of the ALS Functional Rating Scale-Revised (ALSFRS-R), including non-linearity, multidimensionality and floor-effect, have emerged and its usefulness argued. The ALS Milano-Torino staging (ALS-MITOS) system was proposed as a novel tool to measure the progression of ALS and overcome these limitations. This study was performed to validate the ALS-MITOS as a 6-month proxy of survival in 200 ALS patients followed up to 18 months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Analyses were performed on data from the recombinant human erythropoietin RCT that failed to demonstrate differences between groups for both primary and secondary outcomes. The ALS-MITOS system is composed of four key domains included in the ALSFRS-R scale (walking\/self-care, swallowing, communicating and breathing), each with a threshold reflecting the loss of function in the specific ALSFRS-R subscores. Sensitivity, specificity and the area under the curve of the receiver operating characteristic curves of the ALS-MITOS system stages and ALSFRS-R decline at 6 months were calculated and compared with the primary outcome (survival, tracheotomy or &gt;23-hour non-invasive ventilation) at 12 and 18 months Predicted probabilities of the ALS-MITO system at 6 months for any event at 12 and 18 months were computed through logistic regression models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Disease progression from baseline to 6 months as defined by the ALS-MITOS system predicted death, tracheotomy or &gt;23-hour non-invasive ventilation at 12 months with 82% sensitivity (95% CI 71% to 93%, n=37\/45) and 63% specificity (95% CI 55% to 71%, n=92\/146), and at 18 months with 71% sensitivity (95% CI 61% to 82%, n=50\/70) and 68% specificity (95% CI 60% to 77%, n=76\/111). The analysis of ALS-MITOS and ALSFRS-R progression at 6-month follow-up showed that the best cut-off to predict survival at 12 and 18 months was 1 for the ALS-MITOS (ie, loss of at least one function) and a decline ranging from 6 to 9 points for the ALSFRS-R.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The ALS-MITOS system can reliably predict the course of ALS up to 18 months and can be considered a novel and valid outcome measure in RCTs.<\/jats:p><\/jats:sec>","DOI":"10.1136\/jnnp-2014-310176","type":"journal-article","created":{"date-parts":[[2015,4,18]],"date-time":"2015-04-18T02:21:38Z","timestamp":1429323698000},"page":"1180-1185","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":51,"title":["The MITOS system predicts long-term survival in amyotrophic lateral sclerosis"],"prefix":"10.1136","volume":"86","author":[{"given":"Irene","family":"Tramacere","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Dalla Bella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriano","family":"Chi\u00f2","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Mora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graziella","family":"Filippini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Lauria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2015,4,17]]},"reference":[{"key":"key-10.1136\/jnnp-2014-310176-1","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1136\/jnnp-2013-306589","article-title":"Development and evaluation of a clinical staging system for amyotrophic lateral sclerosis","volume":"86","author":"Chio","year":"2015","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"key-10.1136\/jnnp-2014-310176-2","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/nrneurol.2011.153","article-title":"Clinical diagnosis and management of amyotrophic lateral sclerosis","volume":"7","author":"Hardiman","year":"2011","journal-title":"Nat Rev Neurol"},{"key":"key-10.1136\/jnnp-2014-310176-3","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0022-510X(99)00210-5","article-title":"The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function. 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