Atypical neuromyelitis optica spectrum disorder with immunotherapy-responsive neurological symptoms and leukodystrophy-like white matter lesions: A case report

• NMOSD rarely presents with slowly evolving clinical features. • Leukodystrophy-like white matter lesions appeared in NMOSD patients. • Chronic progressive deficits of NMOSD may respond to immunotherapy. Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune neurological disease mediated by anti-aquaporin-4 (AQP4) antibodies. Current diagnostic criteria prioritize AQP4 antibody positivity, enabling diagnosis even in atypical cases. Here, we report an atypical case of AQP4 antibody-positive NMOSD. The patient initially presented with relapsing optic neuritis and, after a prolonged course, developed slowly evolving gait disturbance and cognitive decline with leukoencephalopathy-like white matter lesions on magnetic resonance imaging under treatment with prednisolone. No other relevant autoantibodies except AQP4 antibody were detected. Oligoclonal IgG bands were persistently detected, and interleukin-6 levels were abnormally elevated in cerebrospinal fluid. Neurological deficits and magnetic resonance imaging abnormalities improved following immunotherapy. This case highlights that NMOSD can rarely present with atypical features, including slowly evolving neurological symptoms and leukodystrophy-like imaging findings. It underscores the need for long-term monitoring, even in cases that initially appear typical, as well as the importance of appropriate immunotherapy.