{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T22:22:29Z","timestamp":1791238949471,"version":"4.1.0"},"reference-count":65,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2015,2,16]],"date-time":"2015-02-16T00:00:00Z","timestamp":1424044800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Eugene Devic European Network (EDEN)"},{"name":"Association pour la Recherche contre la Scl\u00e9rose en Plaques (ARSEP) Foundation"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:p>Neuromyelitis optica (<jats:styled-content style=\"fixed-case\">NMO<\/jats:styled-content>) is a rare inflammatory disorder of the central nervous system. The hallmark of <jats:styled-content style=\"fixed-case\">NMO<\/jats:styled-content> is the presence of specific autoantibodies directed against aquaporin 4 (<jats:styled-content style=\"fixed-case\">AQP<\/jats:styled-content>4\u2010IgG). <jats:styled-content style=\"fixed-case\">AQP<\/jats:styled-content>4\u2010IgG, included in diagnostic criteria, has enlarged the clinical spectrum of <jats:styled-content style=\"fixed-case\">NMO<\/jats:styled-content> and serves to predict relapses. Moreover <jats:styled-content style=\"fixed-case\">AQP<\/jats:styled-content>4\u2010IgG has provided unprecedented insight in the immunopathology of <jats:styled-content style=\"fixed-case\">NMO<\/jats:styled-content>, representing a rationale for therapeutic intervention with relevant novel treatment strategies specific for <jats:styled-content style=\"fixed-case\">NMO<\/jats:styled-content>. However, some patients remain seronegative for <jats:styled-content style=\"fixed-case\">AQP<\/jats:styled-content>4\u2010IgG despite a definite diagnosis of <jats:styled-content style=\"fixed-case\">NMO<\/jats:styled-content> and the use of the finest methods for antibody detection. Interestingly, seronegative <jats:styled-content style=\"fixed-case\">NMO<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">NMO<\/jats:styled-content><jats:sup>neg<\/jats:sup>) patients exhibit different demographic and disease\u2010related characteristics in comparison to seropositive patients. The recent association with autoantibodies specific for myelin oligodendrocyte glycoprotein (<jats:styled-content style=\"fixed-case\">MOG<\/jats:styled-content>) is the main indication that disease mechanisms might differ in <jats:styled-content style=\"fixed-case\">NMO<\/jats:styled-content><jats:sup>pos<\/jats:sup> and <jats:styled-content style=\"fixed-case\">NMO<\/jats:styled-content><jats:sup>neg<\/jats:sup>, challenging the position of <jats:styled-content style=\"fixed-case\">NMO<\/jats:styled-content><jats:sup>neg<\/jats:sup> patients in the spectrum of demyelinating diseases and therapeutic strategies to be adopted. Thus, a reappraisal of the <jats:styled-content style=\"fixed-case\">NMO<\/jats:styled-content><jats:sup>neg<\/jats:sup> population is needed to improve <jats:styled-content style=\"fixed-case\">NMO<\/jats:styled-content> care. Here the current knowledge regarding <jats:styled-content style=\"fixed-case\">NMO<\/jats:styled-content><jats:sup>neg<\/jats:sup> is reviewed and hypotheses on its pathogenesis are made including a comprehensive description of detection methods and the prevalence of <jats:styled-content style=\"fixed-case\">AQP<\/jats:styled-content>4\u2010IgG and a review of the epidemiological, clinical and paraclinical characteristics of <jats:styled-content style=\"fixed-case\">NMO<\/jats:styled-content><jats:sup>neg<\/jats:sup>; finally an integrated view of the general pathophysiological mechanisms underlying <jats:styled-content style=\"fixed-case\">NMO<\/jats:styled-content><jats:sup>neg<\/jats:sup> is provided.<\/jats:p>","DOI":"10.1111\/ene.12679","type":"journal-article","created":{"date-parts":[[2015,2,16]],"date-time":"2015-02-16T11:43:19Z","timestamp":1424086999000},"page":"1511","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Neuromyelitis optica: a positive appraisal of seronegative cases"],"prefix":"10.1111","volume":"22","author":[{"given":"R.","family":"Bernard\u2010Valnet","sequence":"first","affiliation":[{"name":"INSERM U1043 CNRS UMR 5282 Centre de Physiopathologie de Toulouse Purpan Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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