Objective:

Characterization of persistent aquaporin-4 immunoglobulin G (AQP4-IgG) seropositivity prior to the clinical onset of neuromyelitis optica spectrum disorder (NMOSD).

Background:

AQP4-IgG is very specific to NMOSD and is important for diagnosis. The importance of isolated seropositivity in patients without typical clinical signs is not well understood.

Design/Methods:

Longitudinal case report with clinical, radiographic, and serologic follow-up over two years.

Results:

A 69-year-old woman with myasthenia gravis and prior focal epilepsy was found to have a transient right frontal ring-enhancing lesion during evaluation of a breakthrough seizure at age 67. Serum testing revealed markedly elevated AQP4-IgG titers (>1:100,000), with negative myelin oligodendrocyte glycoprotein antibodies. She lacked clinical features of neuromyelitis optica spectrum disorder (NMOSD), including optic neuritis, myelitis, and area postrema syndrome. Cerebrospinal fluid analysis was unremarkable, without pleocytosis or oligoclonal bands.Repeat imaging one month later demonstrated complete resolution of the lesion, with residual T2 FLAIR hyperintensity suggestive of a subacute infarct. She remained asymptomatic despite persistent AQP4-IgG seropositivity. At age 69, approximately two years after initial seropositivity, she continued to be clinically stable at follow-up.Three months later, she developed subacute bilateral lower extremity paresthesias. MRI revealed T2–T5 longitudinally extensive transverse myelitis with active cord lesions and a new enhancing left occipital periventricular lesion. She improved following intravenous methylprednisolone and was initiated on satralizumab, confirming a delayed diagnosis of NMOSD.

Conclusions:

This case indicates that AQP4-IgG seropositivity can occur before the clinical onset of NMOSD. It suggests a possible preclinical phase of the disease and raises questions about how to monitor these patients. The delayed progression to longitudinally extensive transverse myelitis after years of isolated seropositivity shows the diagnostic uncertainty in asymptomatic AQP4-IgG positive patients. It also raises important questions about the best surveillance strategies and whether identifying the condition earlier could affect outcomes.