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Neuromyelitis optica spectrum disorder (NMOSD) in elderly patients is an uncommon but severely disabling disease. Rapid diagnosis and treatment are warranted. However, due to the different comorbidities present in the elderly, it is likely to result in misdiagnosis or delayed diagnosis. Herein,we report a case of very-late-onset NMOSD with latent syphilis misdiagnosed as lumbosacral spondylolisthesis in an 80-year-old woman. Our case highlights that timely treatment of co-existing latent syphilis and aquaporin-4 antibody(AQP4-Ab)-positive NMOSD results in an excellent prognosis. NMOSD should be considered in the differential diagnosis of elderly patients with transverse myelitis. In addition, comprehensive investigation and treatment of diseases co-existing with NMOSD are essential.