Background: Neuromyelitis optica spectrum disease (NMOSD) is a chronic inflammatory demyelinating disorder that involves central nervous system (CNS) with high affinity for involvement of optic nerve and spinal cord. In current study, due to high prevalence of NMOSD in Isfahan, Iran, we have aimed to assess brain and spine magnetic resonance imaging (MRI) of patients with NMOSD.Methods: This cross-sectional study was performed on 62 patients with diagnosis of NMOSD, who referred to MS clinic of Kashani hospital, Isfahan City, during 2015-17. Patients' age, age of onset, primary brain and spine MRI findings, and expanded disability status scale (EDSS) were recorded in check list. Patients underwent new brain and spine MRI. Data were analyzed with SPSS software. Descriptive data were reported by mean ± standard deviation (SD).Results: 62 known cases of NMOSD including 9 (14.5%) men and 53 (85.5%) women with mean age of 34.32 ± 10.26 years, mean age of onset of 28.03 ± 12.09 years, and mean EDSS of 2.63 ± 1.55 were assessed. 33.9% of patients were anti-neuromyelitis optica (NMO) antibody seropositive. Longitudinal extensive transverse myelitis (LETM) and segmental spinal lesions were found in 66.1% and 29.0% of patients, respectively. Diagnostic NMO brain lesions and posterior periventricular lesions were seen in 38.7% and 67.7% of patients, respectively. Two patients had tumefactive lesions.Conclusion: In current study, we found high rate of posterior periventricular lesions in brain MRI and segmental lesions in spine MRI of both anti-NMO antibody seropositive and seronegative patients. As these lesions are not in NMOSD diagnosis criteria, more considerations are recommended. In addition, tumefactive lesions in patients with NMOSD were an exciting finding of this study that should be discussed about more.