{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T11:55:42Z","timestamp":1787745342338,"version":"build-2784847793"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T00:00:00Z","timestamp":1670457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of\u00a0Hunan Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disease preferentially affects the optic nerve and the spinal cord. The first attack usually occurs in the third or fourth decade, though patients with disease onset in the fifties or later are not uncommon. This study aimed to investigate the clinical characteristics and prognosis in patients with different age of onset and to explore the correlations between age of onset and clinical characteristics and prognostic outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>We retrospectively reviewed the medical records of 298 NMOSD patients diagnosed according to the 2015 updated version of diagnostic criteria. Patients were divided into early-onset NMOSD (EO-NMOSD) (&amp;lt;50 years at disease onset) and late-onset NMOSD (LO-NMOSD) (\u226550 years at disease onset) based on the age of disease onset. LO-NMOSD patients were divided into two subgroups: relative-late-onset NMOSD (RLO-NMOSD) (50~70 years at disease onset) and very-late-onset NMOSD (\u226570 years at disease onset). Clinical characteristics, laboratory findings, neuroimaging features, and prognostic outcomes were investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compared to EO-NMOSD patients, patients with LO-NMOSD showed more frequent transverse myelitis (TM) (58.20% vs. 36.00%,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.007) while less frequent optic neuritis (ON) (23.10% vs. 34.80%,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.031) and brainstem\/cerebral attacks (7.50% vs. 18.30%,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.006) as the first attack. Patients with LO-NMOSD showed less frequent relapses, higher Expanded Disability Status Scale (EDSS) score at the last follow-up, fewer NMOSD-typical brain lesions, and longer segments of spinal cord lesions. Patients with older onset age showed a higher proportion of increased protein levels in cerebrospinal fluid during the acute phase of attacks. Age at disease onset positively correlated with length of spinal cord lesions at first attack and at last follow-up, negatively correlated with ARR-1 (ARR excluding the first attack, calculated from disease onset to final follow-up), irrespective of AQP4-IgG serostatus. Patients with older age at disease onset progressed to severe motor disability sooner, and age of onset positively correlated with EDSS score at the last follow-up, irrespective of AQP4-IgG serostatus.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Age of disease onset affects clinical characteristics and prognosis outcomes of patients with NMOSD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2022.1056944","type":"journal-article","created":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T00:06:06Z","timestamp":1670457966000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":29,"title":["Age of onset correlates with clinical characteristics and prognostic outcomes in neuromyelitis optica spectrum disorder"],"prefix":"10.3389","volume":"13","author":[{"given":"Yacen","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiying","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyan","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyun","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengchuan","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinxin","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yafang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,12,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(07)70216-8","article-title":"The spectrum of neuromyelitis optica","volume":"6","author":"Wingerchuk","year":"2007","journal-title":"Lancet Neurol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1038\/s41572-020-0214-9","article-title":"Neuromyelitis optica","volume":"6","author":"Jarius","year":"2020","journal-title":"Nat Rev Dis Primers"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001729","article-title":"International consensus diagnostic criteria for neuromyelitis optica spectrum disorders","volume":"85","author":"Wingerchuk","year":"2015","journal-title":"Neurology"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1177\/1352458515572406","article-title":"Demographic and clinical features of neuromyelitis optica: A review","volume":"21","author":"Pandit","year":"2015","journal-title":"Mult Scler"},{"key":"B5","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1186\/s12883-015-0417-y","article-title":"Late-onset neuromyelitis optica spectrum disorder in AQP4-seropositivepatients in a Chinese population","volume":"15","author":"Mao","year":"2015","journal-title":"BMC Neurol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000607","article-title":"Late-onset neuromyelitis optica spectrum disorder: The importance of autoantibody serostatus","volume":"6","author":"Sepulveda","year":"2019","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1177\/1352458516685416","article-title":"Clinical characteristics of late-onset neuromyelitis optica spectrum disorder: A multicenter retrospective study in Korea","volume":"23","author":"Seok","year":"2017","journal-title":"Mult Scler"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/ene.15239","article-title":"Late onset neuromyelitis optica spectrum disorder with anti-aquaporin 4 and anti-myelin oligodendrocyte glycoprotein antibodies","volume":"29","author":"Wang","year":"2022","journal-title":"Eur J Neurol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1590\/0004-282X20130077","article-title":"Neuromyelitis optica with very late onset","volume":"71","author":"Souza","year":"2013","journal-title":"Arq Neuropsiquiatr"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-015-7766-8","article-title":"Very late-onset neuromyelitis optica spectrum disorder beyond the age of 75","volume":"262","author":"Krumbholz","year":"2015","journal-title":"J Neurol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2019.101398","article-title":"Letter to the Editor - late-onset neuromyelitis optica associated with cryptogenic organizing pneumonia","volume":"36","author":"Oliveira","year":"2019","journal-title":"Mult Scler Relat Disord"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-021-10913-y","article-title":"Lethal form of a late-onset aquaporin-4 antibody-positive NMOSD related to the immune checkpoint inhibitor nivolumab","volume":"269","author":"Weiss","year":"2022","journal-title":"J Neurol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2020.102515","article-title":"Clinical characteristics of very late-onset neuromyelitis optica spectrum disorder","volume":"46","author":"Cai","year":"2020","journal-title":"Mult Scler Relat Disord"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1111\/ene.14901","article-title":"Very late onset neuromyelitis optica spectrum disorders","volume":"28","author":"Nakahara","year":"2021","journal-title":"Eur J Neurol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.33.11.1444","article-title":"Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS)","volume":"33","author":"Kurtzke","year":"1983","journal-title":"Neurology"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001367","article-title":"MRI Characteristics of neuromyelitis optica spectrum disorder: an international update","volume":"84","author":"Kim","year":"2015","journal-title":"Neurology"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-020-09699-2","article-title":"Clinical features and prognosis of late-onset neuromyelitis optica spectrum disorders in a Latin American cohort","volume":"267","author":"Carnero Contentti","year":"2020","journal-title":"J Neurol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2011-300403","article-title":"Clinical features of neuromyelitis optica in a large Japanese cohort: comparison between phenotypes","volume":"82","author":"Nagaishi","year":"2011","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2007-2758","article-title":"Spectrum of pediatric neuromyelitis optica","volume":"122","author":"Lotze","year":"2008","journal-title":"Pediatrics"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2014-308550","article-title":"Paediatric neuromyelitis optica: clinical, MRI of the brain and prognostic features","volume":"86","author":"Absoud","year":"2015","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000237475.01655.9d","article-title":"Is late-onset multiple sclerosis associated with a worse outcome","volume":"67","author":"Tremlett","year":"2006","journal-title":"Neurology"},{"key":"B22","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1007\/s00415-008-0778-x","article-title":"Clinical characteristics of patients with late-onset multiple sclerosis","volume":"255","author":"Kis","year":"2008","journal-title":"J Neurol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1002\/ana.25909","article-title":"Clinical features and risk of relapse in children and adults with myelin oligodendrocyte glycoprotein antibody-associated disease","volume":"89","author":"Cobo-Calvo","year":"2021","journal-title":"Ann Neurol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"e2142780","DOI":"10.1001\/jamanetworkopen.2021.42780","article-title":"Factors associated with relapse and treatment of myelin oligodendrocyte glycoprotein antibody-associated disease in the united kingdom","volume":"5","author":"Satukijchai","year":"2022","journal-title":"JAMA Netw Open"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws109","article-title":"Prognostic factors and disease course in aquaporin-4 antibody-positive patients with neuromyelitis optica spectrum disorder from the united kingdom and Japan","volume":"135","author":"Kitley","year":"2012","journal-title":"Brain"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1177\/1352458513515085","article-title":"Characterization of neuromyelitis optica and neuromyelitis optica spectrum disorder patients with a late onset","volume":"20","author":"Collongues","year":"2014","journal-title":"Mult Scler"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000009245","article-title":"Evaluation of efficacy and tolerability of first-line therapies in NMOSD","volume":"94","author":"Poupart","year":"2020","journal-title":"Neurology"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2022.859276","article-title":"Relatively early and late-onset neuromyelitis optica spectrum disorder in central China: Clinical characteristics and prognostic features","volume":"13","author":"Yu","year":"2022","journal-title":"Front Neurol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2020.102258","article-title":"Age at onset correlate with disability in Latin American aquaporin-4-IgG-positive NMOSD patients","volume":"44","author":"Carnero Contentti","year":"2020","journal-title":"Mult Scler Relat Disord"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1080\/00207454.2016.1254630","article-title":"Distinctive characteristics of early-onset and late-onset neuromyelitis optica spectrum disorders","volume":"127","author":"Zhang","year":"2017","journal-title":"Int J Neurosci"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.2011.03435.x","article-title":"Neuromyelitis optica with very late onset","volume":"59","author":"Lefaucheur","year":"2011","journal-title":"J Am Geriatr Soc"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1177\/1352458515572241","article-title":"Neuromyelitis optica spectrum disorder as a paraneoplastic manifestation of lung adenocarcinoma expressing aquaporin-4","volume":"21","author":"Iorio","year":"2015","journal-title":"Mult Scler"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jneuroim.2017.04.006","article-title":"Late onset neuromyelitis optica mimicking an acute stroke in an elderly patient","volume":"309","author":"Suchdev","year":"2017","journal-title":"J Neuroimmunol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.ensci.2018.11.008","article-title":"Two cases of late-onset neuromyelitis optica spectrum disorder initially presenting with isolated cerebral white matter lesions","volume":"13","author":"Otani","year":"2018","journal-title":"eNeurologicalSci"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2019.577051","article-title":"Very late-onset recurrent myelitis in a patient diagnosed with antiphospholipid syndrome: A puzzle of autoimmunity","volume":"337","author":"Margoni","year":"2019","journal-title":"J Neuroimmunol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1159\/000505231","article-title":"Two cases of very-Late-Onset neuromyelitis optica spectrum disorder (NMOSD) in patients over the age of 80","volume":"12","author":"Fujiwara","year":"2020","journal-title":"Case Rep Neurol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1159\/000509859","article-title":"Very-Late-Onset neuromyelitis optica spectrum disorder in a patient with breast cancer and Parkinson disease","volume":"13","author":"Tajima","year":"2021","journal-title":"Case Rep Neurol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1080\/10790268.2020.1749475","article-title":"Late-onset neuromyelitis optica spectrum disorder mimicking stroke in an elderly Chinese man: Case report","volume":"45","author":"Li","year":"2022","journal-title":"J Spinal Cord Med"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1159\/000515555","article-title":"Clinical characteristics of Chinese Male patients with aquaporin-4 antibody-positive late-onset neuromyelitis optica spectrum disorder","volume":"28","author":"Liang","year":"2021","journal-title":"Neuroimmunomodulation"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.1056944\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T00:06:09Z","timestamp":1670457969000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.1056944\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,8]]},"references-count":39,"alternative-id":["10.3389\/fimmu.2022.1056944"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.1056944","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,8]]},"article-number":"1056944"}}