Objective:

Describe a patient with prior AQP4-IgG seropositivity with a new brainstem attack in the absence of detectable AQP4-IgG.

Background:

Neuromyelitis optica spectrum disorder (NMOSD) is associated with antibodies directed against aquaporin 4 (AQP4-IgG) resulting in attacks of optic neuritis, longitudinally extensive transverse myelitis (LETM), or area postrema syndrome. Symptoms may present simultaneously or asynchronously.

Design/Methods:

Data was obtained from retrospective chart review, laboratory testing, and brain MRI. Laboratory testing included AQP4-IgG testing by enzyme-linked immunoassay (ELISA), cell-based assay (CBA) indirect fluorescent antibody (CBA-IFA) and CBA fluorescence-activated cell-sorting (CBA-FACS).

Results:

A 43-year-old previously healthy female was diagnosed with NMOSD in 2012 after presenting with LETM; laboratory testing was positive for AQP4-IgG by ELISA (30 U/mL). Rituximab was started, but after negative repeat ELISA, she declined further treatment. Interval AQP4-IgG showed positivity on ELISA (peak 10 U/mL) and FACS assay (peak 1:10000) from 2015-2017; in 2018, CBA-FACS was negative. She remained clinically stable until 2021 when she experienced five weeks of area postrema syndrome. AQP4-IgG CBA-IFA was negative; MRI showed a new enhancing posterior brainstem lesion. Treatment included five days of IV methylprednisolone and five rounds of plasma exchange with resolution of symptoms. Rituximab was started and she has remained clinically stable with continued seronegativity on CBA-FACS assay.

Conclusions:

This patient fulfilled 2015 criteria for seropositive NMOSD in 2012 then seronegative NMOSD in 2021, with one relapse seven years after cessation of treatment and four years after peak AQP4-Ab titer. A recent retrospective longitudinal analysis revealed 11% of seropositive patients within the study became seronegative; in contrast to this case, they frequently had low initial titers at onset. This case raises key questions: Does antibody presence fluctuate naturally without treatment? Are antigenic spread or cellular immunity involved with seronegative attacks?