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In MSA, previous studies on trajectories of disease did not include stridor and REM sleep behavior disorder (RBD) as clinical variable.<\/jats:p>\n            <jats:p>The aims of the study were: (1) to investigate disease progression in MSA patients with early stridor onset and with early stridor and\/or RBD onset; (2) to assess cerebrospinal fluid (CSF) levels of neurofilament light chain protein (NfL) in MSA patients with early onset sleep disorders.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>This is a retrospective and prospective cohort study including 208 (120 males) MSA patients. Occurrence of symptoms\/signs, milestones of disease progression, and their latency from disease onset were collected. RBD and stridor were video-polysomnography (VPSG)-confirmed. CSF NfL levels were analyzed. Survival data and predictors of mortality were calculated.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Out of 208 MSA patients (157 deceased), 91 were diagnosed with stridor and 160 with VPSG-confirmed RBD. Patients with early stridor onset (<jats:italic>n<\/jats:italic>\u2009=\u200941) and with early stridor and\/or RBD onset (<jats:italic>n<\/jats:italic>\u2009=\u2009132) showed an early autonomic involvement, developed a more progressive and severe disease and presented higher CSF NfL than those with late stridor and RBD onset. Early stridor and early RBD were independent risk factors on MSA survival.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>The evidence of a more rapid and severe disease progression and of high CSF NfL levels in patients who early developed sleep disorders could define a different MSA phenotype with a widespread impairment of central-brainstem circuits.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00415-025-12969-6","type":"journal-article","created":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T09:21:06Z","timestamp":1740820866000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Early onset sleep disorders predict severity, progression and death in multiple system atrophy"],"prefix":"10.1007","volume":"272","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0499-3236","authenticated-orcid":false,"given":"Giulia","family":"Giannini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3666-1735","authenticated-orcid":false,"given":"Luca","family":"Baldelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9063-2658","authenticated-orcid":false,"given":"Federica","family":"Provini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9189-1982","authenticated-orcid":false,"given":"Ilaria","family":"Cani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7702-7856","authenticated-orcid":false,"given":"Simone","family":"Baiardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5939-7933","authenticated-orcid":false,"given":"Luisa","family":"Sambati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3894-8419","authenticated-orcid":false,"given":"Franco","family":"Magliocchetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0597-603X","authenticated-orcid":false,"given":"Pietro","family":"Guaraldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9444-9524","authenticated-orcid":false,"given":"Piero","family":"Parchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3633-8818","authenticated-orcid":false,"given":"Pietro","family":"Cortelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9447-3532","authenticated-orcid":false,"given":"Giovanna","family":"Calandra-Buonaura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,1]]},"reference":[{"key":"12969_CR1","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1002\/mds.29005","volume":"37","author":"GK Wenning","year":"2022","unstructured":"Wenning GK, Stankovic I, Vignatelli L et al (2022) The movement disorder society criteria for the diagnosis of multiple system atrophy. 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Outside the present work, Dr. Giannini has received honoraria for speaking engagements or consulting activities from Bial;\u2014Dr. Baldelli reports no disclosures.\u2014Prof. Provini reports no disclosures. Outside the present work, Prof. Provini has received honoraria for speaking engagements or consulting activities from Italfarmaco, Idorsia, and Neopharmed Gentili S.p.A., and has received a grant from the Italian Ministry of Health (PNRR-MCNT2-2023\u201312377357);\u2014Dr. Cani reports no disclosures. Outside the present work, Dr. Cani has received honoraria for speaking engagements or consulting activities from Bial;\u2014Dr. Baiardi reports no disclosures.\u2014Dr. Sambati reports no disclosures. Outside the present work, Dr. Sambati has received honoraria for speaking engagements or consulting activities from Bial and Roche;\u2014Dr. Magliocchetti reports no disclosures.\u2014Dr. Guaraldi reports no disclosures. Outside the present work, Dr. Guaraldi has received honoraria for speaking engagements or consulting activities from Alnylam;\u2014Prof. Parchi reports no disclosures. Outside the present work, Prof. Parchi has received grants from the Italian Ministry of Health\u2014PNRR 2023 (PNRR-MCNT2-2023\u201312378190) and from the EU Joint Program for Neurodegenerative Diseases (JPND, Transnational 2023 research call, Project Title: \u201cPrionomics\u201d);\u2014Prof. Cortelli reports no disclosures. Outside the present work, Prof. Cortelli has received honoraria for speaking engagements or consulting activities from Jazz Pharmaceuticals, Abbvie, Zambon, Lundbeck;\u2014Prof. Calandra-Buonaura reports no disclosures. Outside the present work, Prof. Calandra-Buonaura has received honoraria for speaking engagements or consulting activities from Bial.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The study was conducted in agreement with the principles of good clinical practice. The study protocol was approved by the local ethics committee of the local health service of Bologna, Italy (Cod. CE: 09070 and 17093). All patients gave written informed consent for study participation.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"239"}}