{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T23:12:17Z","timestamp":1790291537326,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T00:00:00Z","timestamp":1759104000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T00:00:00Z","timestamp":1759104000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2026,2]]},"abstract":"\n Objective<\/jats:title>\n \n The primary lateral sclerosis (\n PLS<\/jats:styled-content>\n ) consensus diagnostic criteria and functional rating scale (\n PLSFRS<\/jats:styled-content>\n ) were recently established to facilitate and optimize future\n PLS<\/jats:styled-content>\n clinical trials. We examined the trajectory of the\n PLSFRS<\/jats:styled-content>\n and other functional outcome measures and biomarkers in the\n PLS<\/jats:styled-content>\n Natural History Study (\n PLS NHS<\/jats:styled-content>\n ) to understand their performance in this prospective cohort.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n The\n PLS NHS<\/jats:styled-content>\n is a prospective, longitudinal, multicenter study of people living with\n PLS<\/jats:styled-content>\n in different diagnostic categories: early (disease duration <2\u2009years); probable (2\u20134\u2009years); and definite\n PLS<\/jats:styled-content>\n (4\u201315\u2009years).\n PLSFRS<\/jats:styled-content>\n scores and other functional outcome measures were collected at baseline, 3\u2010, 6\u2010, 9\u2010, and 12\u2010month follow\u2010up visits. Baseline characteristics were compared between the groups. The slopes of the\n PLSFRS<\/jats:styled-content>\n and other functional outcome measures over 12\u2009months were examined in the overall cohort and subgroups using linear mixed\u2010effect models. The associations between baseline characteristics and the rate of\n PLSFRS<\/jats:styled-content>\n decline were analyzed with linear regression models.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 76 participants were included: early (n\u2009=\u20096); probable (n\u2009=\u200926); and definite (n\u2009=\u200944)\n PLS<\/jats:styled-content>\n . Baseline\n PLSFRS<\/jats:styled-content>\n total scores were highest in the early\n PLS<\/jats:styled-content>\n group, followed by the probable and definite\n PLS<\/jats:styled-content>\n groups. In the overall cohort, the\n PLSFRS<\/jats:styled-content>\n total score declined by 0.33 points\/month (95% confidence interval [0.27\u20130.39], adjusted\n p<\/jats:italic>\n \u2009<\u20090.05). The rate of decline was steepest in the early\n PLS<\/jats:styled-content>\n group, followed by the probable and definite\n PLS<\/jats:styled-content>\n groups. Baseline neurofilament light chain level was associated with the rate of\n PLSFRS<\/jats:styled-content>\n decline over 1\u2009year (\n p<\/jats:italic>\n \u2009=\u20090.001).\n <\/jats:p>\n <\/jats:sec>\n \n Interpretation<\/jats:title>\n In PLS, the rate of functional decline, as measured by the PLSFRS total score, is faster during the early phase of the disease. Neurofilament light might serve as a prognostic biomarker in PLS. ANN NEUROL 2026;99:418\u2013428<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/ana.78056","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T11:30:43Z","timestamp":1759145443000},"page":"418-428","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Primary Lateral Sclerosis Natural History Study:\n Primary Lateral Sclerosis Functional Rating Scale<\/scp>\n and Other Outcomes Assessment"],"prefix":"10.1002","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0537-9622","authenticated-orcid":false,"given":"Ikjae","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Neurology Columbia University Irving Medical Center New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Neurology Columbia University Irving Medical Center New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying Kuen (Ken)","family":"Cheung","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Mailman School of Public Health Columbia University New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander V.","family":"Sherman","sequence":"additional","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy S.","family":"Johnston","sequence":"additional","affiliation":[{"name":"Division of Neurology University of Alberta Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3526-1852","authenticated-orcid":false,"given":"Frank","family":"Diaz","sequence":"additional","affiliation":[{"name":"Department of Neurology Cedars\u2010Sinai Medical Center Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Americo M.","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences University of Nebraska Medical Center Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali A.","family":"Habib","sequence":"additional","affiliation":[{"name":"Department of Neurology University of California Irvine Orange California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7311-9614","authenticated-orcid":false,"given":"Nicholas J.","family":"Maragakis","sequence":"additional","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Paganoni","sequence":"additional","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital Harvard Medical School Boston Massachusetts USA"},{"name":"Department of PM&R Spaulding Rehabilitation Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Burke","sequence":"additional","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital Harvard Medical School Boston Massachusetts USA"},{"name":"School of Health and Rehabilitation Sciences Institute of Health Professions Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1725-9866","authenticated-orcid":false,"given":"Bjorn","family":"Oskarsson","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic Jacksonville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaimin","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic Jacksonville Florida 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