To explore the clinical features in neuromyelitis optica spectrum disorders (NMOSD) and analyze the heterogeneity of atypical clinical manifestations. Methods: The clinical data of 36 patients with NMOSD were collected. Their clinical profiles, MRI features, laboratory examination, treatment, and prognosis were analyzed. Results: Of the 36 patients, the male to female ratio was 7∶29. The average age was (43.5±6.4) years. There were 2 cases with history of hyperthyroidism, 1 case with history of allergic asthma, and 1 case with history of Sjogren’s syndrome. Initial manifestations include intractable nausea and vomiting in 4 cases, paresthesia in 4 cases, hypogeusia in 1 case, optic neuritis symptoms in 10 cases, and myelitis symptoms in 17 cases. The ratio of atypical initial manifestations was 5/36. There were 14 cases that were positive for serum AQP4-IgG (14/32) and 10 cases that were positive for serum MOG-IgG (10/25). Magnetic resonance imaging (MRI) showed abnormal signals in the cerebral cortex, midbrain, pons, oblongata, and spinal cord. All 36 patients were treated with glucocorticoid; among them, 1 received plasmapheresis and 5 received azathioprine by oral dosage. Follow up showed that 25 patients experienced different degrees of sequelae. Conclusion: Neuromyelitis optica spectrum disorders frequently occur in young females. Some cases may exist in combination with other autoimmune diseases. Manifestations in the initial stage and course of disease vary greatly. Lesions occur mainly in the optic nerve, spinal cord, and brain. NMOSD should be considered in patients with atypical clinical manifestations