Background and purpose: To determine the diagnostic value of bright spotty lesions (BSLs) for aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (NMOSDAQP4+), the predictive value of axial-BSLs for AQP4-IgG seropositivity, and the radio-clinical differences in NMOSDAQP4+ patients with and without axial-BSLs. Materials and methods: Retrospective study that included patients aged≥16 years, with a first acute spinal cord syndrome between 2005 and 2018 and abnormal spinal cord MRI with axial and sagittal T2 sequences. Patients with MRI findings consistent with compressive myelopathy were excluded. All spinal cord MRI were retrospectively evaluated for the presence of BSLs by 2 radiologists blinded to the diagnosis of acute myelopathy. Results: A total of 82 patients were included; 15 aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder patients (NMOSDAQP4+), and 67 other patients, considered as the other causes of myelopathy (OM) group. The specificity of axial-BSLs for NMOSDAQP4+ patients was 94.0% (95% CI [85.6 to 97.7]). The sensitivity was 40.0% (95% CI [19.8 to 64.3]). In the multivariable analysis, the only MRI characteristic associated with AQP4-IgG positivity was the presence of axial-BSLs (OR: 9.2, 95% CI [1.2 to 72.9]; P=0.022). In NMOSDAQP4+ patients, the median of cord expansion ratio was higher with axial-BSL (1.2, IQR [1.1-1.3]) than without axial-BSL (1.1, IQR [1.0-1.2]; P=0.046). Conclusion: After a first acute spinal cord syndrome, the presence of axial-BSLs on spinal cord MRI seems very specific for NMOSDAQP4+ and seems to be a predictor radiological marker of AQP4-IgG positivity.