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Background  Early stage neuromyelitis optica spectrum disorders (NMOSD) with non-opticospinal manifestations as initial symptoms are easily misdiagnosed; however, data on the full symptom profile are limited. Moreover, the clinical characteristics and long-term outcomes of these patients remain unknown. We sought to analyze the clinical characteristics, imaging features, and long-term outcomes of NMOSD with non-opticospinal manifestations as initial symptoms.    Methods  We retrospectively included relevant patients from our center. Clinical, demographic, magnetic resonance imaging, treatment, and outcome data were compared according to the non-opticospinal vs. opticospinal initial symptoms.    Results  We identified 43 (9.13 %) patients with non-opticospinal initial symptoms among 471 patients with NMOSD. Of these, 88.37 % developed optic neuritis/myelitis during an average follow-up period of 6.33 years. All the non-opticospinal symptoms were brain/brainstem symptoms. Most of the symptoms and associated brain lesions were reversible. These patients had a younger onset age ( P  < 0.001), lower serum aquaporin-4 (AQP4) antibody titers ( P  = 0.030), and a lower Expanded Disability Status Scale (EDSS) score at onset ( P  < 0.001) and follow-up ( P  = 0.041) than NMOSD patients with opticospinal initial symptoms. In addition, EDSS scores reached 3.0 (indicating moderate disability) later than in patients with opticospinal initial symptoms ( P  = 0.028).    Conclusions  Patients with NMOSD with non-opticospinal initial symptoms have a younger onset age, lower serum AQP4 antibody titers, and better clinical outcomes.

Neuromyelitis optica spectrum disorders with non opticospinal manifestations as initial symptoms: a long-term observational study