{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T05:45:38Z","timestamp":1775799938701,"version":"3.50.1"},"reference-count":27,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"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":["Ann Clin Transl Neurol"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Central nervous system (CNS) inflammatory demyelinating syndromes, including multiple sclerosis (MS), aquaporin\u20104 antibody\u2013positive neuromyelitis optica spectrum disorder (AQP4\u2009+\u2009NMOSD), and myelin oligodendrocyte glycoprotein (MOG) antibody\u2013associated disease (MOGAD), occasionally overlap. Some patients remain double\u2010seronegative, showing atypical features that challenge current classifications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To better characterize the phenotypic spectrum of antibody\u2010negative atypical inflammatory demyelinating disorders (AIDD) using unsupervised clustering.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively analyzed 316 patients (MS\u2009=\u2009164, AQP4\u2009+\u2009NMOSD\u2009=\u200936, double\u2010seronegative NMOSD\u2009=\u200921, MOGAD\u2009=\u200915, AIDD\u2009=\u200980) followed between 2010 and 2023. Principal component analysis and k\u2010means clustering were applied to AIDD cases using clinical, demographic, and radiological data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>AIDD patients had lower disability and fewer corpus callosum and posterior fossa lesions than MS and NMOSD. Three clusters emerged: (1) myelitis\u2010predominant with unmatched CSF oligoclonal bands and longitudinally extensive spinal lesions, (2) brainstem\u2010dominant with recurrent brainstem attacks, and (3) optic neuritis\u2010dominant with recurrent LEON meeting MS dissemination criteria. Treatment patterns differed; rituximab was most frequent.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Double\u2010seronegative AIDD represents a heterogeneous clinical spectrum. Unsupervised clustering provides a data\u2010driven framework for refining phenotypic classification and may support biomarker and therapeutic development in antibody\u2010negative CNS demyelination.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.70389","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T04:47:10Z","timestamp":1775796430000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Understanding Further the Phenotypic Spectrum of Central Nervous System Inflammatory Demyelinating Disorders Using Unsupervised Clustering"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2340-4409","authenticated-orcid":false,"given":"Bade","family":"Gulec","sequence":"first","affiliation":[{"name":"Department of Neurology Cerrahpasa Medical Faculty, Istanbul University\u2010Cerrahpasa  Istanbul Turkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elif","family":"Everest","sequence":"additional","affiliation":[{"name":"Department of Neurology Cerrahpasa Medical Faculty, Istanbul University\u2010Cerrahpasa  Istanbul Turkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9851-7002","authenticated-orcid":false,"given":"Melih","family":"Tutuncu","sequence":"additional","affiliation":[{"name":"Department of Neurology Cerrahpasa Medical Faculty, Istanbul University\u2010Cerrahpasa  Istanbul Turkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ugur","family":"Bilge","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Medical Informatics Faculty of Medicine, Akdeniz University  Antalya Turkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabahattin","family":"Saip","sequence":"additional","affiliation":[{"name":"Department of Neurology Cerrahpasa Medical Faculty, Istanbul University\u2010Cerrahpasa  Istanbul Turkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ugur","family":"Uygunoglu","sequence":"additional","affiliation":[{"name":"Department of Neurology Cerrahpasa Medical Faculty, Istanbul University\u2010Cerrahpasa  Istanbul Turkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aksel","family":"Siva","sequence":"additional","affiliation":[{"name":"Department of Neurology Cerrahpasa Medical Faculty, Istanbul University\u2010Cerrahpasa  Istanbul Turkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"issue":"2","key":"e_1_2_12_2_1","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/S1474-4422(17)30470-2","article-title":"Diagnosis of Multiple Sclerosis: 2017 Revisions of the McDonald Criteria","volume":"17","author":"Thompson A. 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