{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T03:53:39Z","timestamp":1777953219363,"version":"3.51.4"},"reference-count":12,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T00:00:00Z","timestamp":1772409600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T00:00:00Z","timestamp":1772409600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100017026","name":"Spastic Paraplegia Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000971","name":"ALS Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000971","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012351","name":"Mitsubishi Tanabe Pharma Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012351","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2026,6]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n Primary lateral sclerosis (PLS) is an ultrarare upper motor neuron syndrome with a prognosis unique from classical ALS. The study of PLS is complicated by its rarity and the difficulty distinguishing PLS from ALS. We present data from a 1\u2010year prospective follow\u2010up study on PLS and efforts to distinguish it from ALS.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Seventy\u2010six PLS participants enrolled in this prospective natural history study. EMG studies, blood neurofilament light chain levels (NfLs), and demographic characteristics were obtained at baseline. At 1\u2010year follow\u2010up, repeat EMG studies were conducted to determine which participants fulfilled criteria for ALS. Baseline characteristics were then compared to determine features that predict reclassification.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Seventy participants completed 1\u2010year follow\u2010up. Five of the 70 were reclassified to ALS (7.1%). Those reclassified had higher trends in baseline blood NfL levels (91.4 vs. 34.0\u2009pg\/mL,\n p<\/jats:italic>\n \u2009=\u20090.13) and shorter symptom duration (39 vs. 69\u2009months in the PLS group,\n p<\/jats:italic>\n \u2009=\u20090.15). Reclassification was noted in both probable and definite PLS participants. All cases with a symptomatic duration of less than 2\u2009years retained the PLS phenotype (5 of 5). NfL levels over 90\u2009pg\/mL predicted reclassification with 94% specificity and 60% sensitivity. No other features predicted reclassification to ALS.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n In our population, reclassification of PLS to ALS occurred at a low frequency at 1\u2009year follow\u2010up (7.1%). Baseline NfL was the strongest predictor in differentiating UMN dominant ALS from PLS at 1\u2010year follow\u2010up. Based on our data, we propose EMG and NfL criteria for enrollment in future PLS trials.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/mus.70192","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T10:07:39Z","timestamp":1772964459000},"page":"976-983","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prospective Validation of the New\n PLS<\/scp>\n Diagnostic Criteria From\n PLS<\/scp>\n Natural History Study:\n EMG<\/scp>\n and Neurofilament Analyses"],"prefix":"10.1002","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7773-7754","authenticated-orcid":false,"given":"Eric","family":"Sorenson","sequence":"first","affiliation":[{"name":"Department of Neurology Mayo Clinic Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daragh","family":"Heitzman","sequence":"additional","affiliation":[{"name":"Texas Neurology Dallas Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0537-9622","authenticated-orcid":false,"given":"Ikjae","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurology Columbia University Irving Medical Center New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grace","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Neurology Columbia University Irving Medical Center New York New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren","family":"Elman","sequence":"additional","affiliation":[{"name":"Department of Neurology, Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali A.","family":"Habib","sequence":"additional","affiliation":[{"name":"Department of Neurology University of California Orange California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Wymer","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Florida College of Medicine Gainesville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ghazala","family":"Hayat","sequence":"additional","affiliation":[{"name":"Department of Neurology Saint Louis University Saint Louis Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen A.","family":"Goutman","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Michigan Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. Americo M.","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences University of Nebraska Medical Center Omaha Nebraska USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary Kay","family":"Floeter","sequence":"additional","affiliation":[{"name":"Clinical Neurosciences Program NINDS Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Senda","family":"Ajroud\u2010Driss","sequence":"additional","affiliation":[{"name":"Department of Neurology Northwestern University Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7589-8826","authenticated-orcid":false,"given":"Kelly","family":"Gwathmey","sequence":"additional","affiliation":[{"name":"Department of Neurology Virginia Commonwealth University Richmond Virginia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward","family":"Kasarskis","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Kentucky Lexington Kentucky USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasushi Y.","family":"Kisanuki","sequence":"additional","affiliation":[{"name":"Department of Neurology The Ohio State University Wexner Medical Center Columbus Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Lomen\u2010Hoerth","sequence":"additional","affiliation":[{"name":"Department of Neurology University of California San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7941-1993","authenticated-orcid":false,"given":"David","family":"Walk","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Minnesota Minneapolis Minnesota 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Physical Medicine and Rehabilitation Spaulding Rehabilitation Hospital Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4379-0666","authenticated-orcid":false,"given":"Jaimin","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic Jacksonville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bjorn","family":"Oskarsson","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic Jacksonville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorne","family":"Zinman","sequence":"additional","affiliation":[{"name":"Department of Neurology Sunnybrook Health Sciences Centre Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terry","family":"Heiman\u2010Patterson","sequence":"additional","affiliation":[{"name":"Department of Neurology Temple University 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