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Although it is a major subtype of autoimmune encephalitis, many unmet clinical needs exist in terms of clinical characteristics, treatments and prognosis. In this institutional cohort study, patients diagnosed with seronegative autoimmune encephalitis with available 2-year outcomes were analysed for the disease course, 2-year outcome prediction system, effect of immunotherapy, necessity of further immunotherapy at 6 or 12 months and pattern of brain atrophy. Seronegative autoimmune encephalitis was subcategorized into antibody-negative probable autoimmune encephalitis, autoimmune limbic encephalitis and acute disseminated encephalomyelitis. Poor 2-year outcome was defined by modified Rankin scale scores 3\u20136, and the 2-year serial data of Clinical Assessment Scales in Autoimmune Encephalitis score was used for longitudinal data analyses. A total of 147 patients were included. The frequency of achieving a good 2-year outcome (modified Rankin scale 0\u20132) was 56.5%. The antibody-negative probable autoimmune encephalitis subtype exhibited the poorest outcomes, although the baseline severity was similar among the subtypes. The RAPID score, consisting of five early usable clinical factors, refractory status epilepticus, age of onset \u226560 years, probable autoimmune encephalitis (antibody-negative probable autoimmune encephalitis subtype), infratentorial involvement and delay of immunotherapy \u22651 month, was associated with poorer 2-year outcomes. Any immunotherapy was associated with clinical improvement in the patients with low risk for poor 2-year outcomes (RAPID scores 0\u20131), and the combination immunotherapy of steroid, immunoglobulin, rituximab and tocilizumab was associated with better outcomes in the patients with high risk for poor 2-year outcomes (RAPID scores 2\u20135). In patients with persistent disease at 6 months, continuing immunotherapy was associated with more improvement, while the effect of continuing immunotherapy for more than 12 months was unclear. In the longitudinal analysis of MRI, the development of cerebellar atrophy indicated poor outcomes, while the absence of diffuse cerebral atrophy or medial temporal atrophy indicated the possibility of a good outcome. This study provides information about the clinical characteristics and courses, the effect of immunotherapy and its duration, and prognostic factors in seronegative autoimmune encephalitis.<\/jats:p>","DOI":"10.1093\/brain\/awac166","type":"journal-article","created":{"date-parts":[[2022,5,4]],"date-time":"2022-05-04T07:18:59Z","timestamp":1651648739000},"page":"3509-3521","source":"Crossref","is-referenced-by-count":123,"title":["Seronegative autoimmune encephalitis: clinical characteristics and factors associated with outcomes"],"prefix":"10.1093","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6090-7921","authenticated-orcid":false,"given":"Woo-Jin","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Neurology, Seoul National University Hospital , Jongno-gu, Seoul 03080 , South Korea"},{"name":"Department of Neurology, Seoul National University Bundang Hospital , Bundang-gu, Seongnam-si 13620 , South 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