Neuromyelitis optica spectrum disorder presenting as rapidly progressive dementia: A case report

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune astrocytopathy primarily affecting the optic nerves and spinal cord. Diencephalic involvement is commonly detected on neuroimaging but often remains clinically silent. Rapidly progressive dementia (RPD) as the initial and primary manifestation of NMOSD is exceedingly rare.

A 64-year-old woman presented with a 10-day history of progressive cognitive slowing and memory decline. On admission, she was disoriented, apathetic, and unable to recognize her family members, with a Mini-Mental State Examination (MMSE) score of 3/30. Laboratory investigations revealed severe hyponatremia (serum sodium 112.60 mmol/L). Brain magnetic resonance imaging showed abnormal signal intensities involving the bilateral basal ganglia, hypothalamus, and mammillary bodies.

Autoimmune encephalitis, infectious encephalitis, Wernicke encephalopathy, and prion disease were initially considered and systematically excluded. Serum and cerebrospinal fluid testing revealed positive aquaporin-4 (AQP-4) antibodies with titers of 1:32 and 1:16, respectively. Based on the 2015 International Panel for NMO Diagnosis criteria, a final diagnosis of AQP-4 antibody-positive NMOSD was established.

The patient received intravenous methylprednisolone pulse therapy (1000 mg/d for 3 days, followed by a stepwise tapering regimen) and gradual correction of electrolyte disturbances.

After 4 weeks of treatment, the patient showed marked cognitive improvement, with the MMSE score increasing from 3 to 18. At the 6-month follow-up, her clinical symptoms had almost completely resolved, the MMSE score had improved to 27/30, electrolyte levels had normalized, and follow-up magnetic resonance imaging demonstrated a significant reduction in lesion size with mild enlargement of the third ventricle.

This case demonstrates that AQP-4 antibody-positive NMOSD can present as a reversible RPD, potentially mediated by AQP-4 antibody-associated inflammatory injury of the diencephalon. It underscores that in patients with unexplained RPD - particularly when neuroimaging reveals lesions in AQP-4-enriched regions such as the hypothalamus, mammillary bodies, or periventricular areas surrounding the third ventricle, or when otherwise unexplained hyponatremia is present - NMOSD should be included in the differential diagnosis. Timely AQP-4 antibody testing should be pursued to facilitate early immunotherapy and optimize clinical outcomes.