AQP4negative

AQP4negative refers to cases of neuromyelitis optica spectrum disorders (NMOSD) in which serum antibodies against aquaporin-4 (AQP4-IgG) are not detected by standard tests. AQP4-IgG is a highly specific biomarker for many NMOSD patients, and seropositivity guides diagnosis and treatment. A substantial minority of NMOSD patients are AQP4-IgG negative; some of these cases are true seronegative NMOSD, while others are now recognized as MOG-IgG-associated disease (MOGAD) or other CNS inflammatory conditions. AQP4-negative status does not exclude NMOSD.

Clinical features overlap with AQP4-positive NMOSD and include optic neuritis and longitudinally extensive transverse myelitis, as well as area postrema syndrome (intractable nausea and vomiting), brainstem, diencephalic, or cerebral involvement. Diagnosis relies on core clinical characteristics supported by neuroimaging and CSF findings, and requires careful exclusion of alternative diagnoses. Because AQP4-IgG testing can be falsely negative, high-sensitivity cell-based assays are preferred; if AQP4-IgG is negative, testing for MOG-IgG is recommended to identify MOGAD, which is considered a distinct disease.

Treatment follows NMOSD principles: acute attacks are treated with high-dose intravenous corticosteroids; plasmapheresis is used for steroid-refractory cases. Long-term relapse prevention employs immunosuppressive therapies such as rituximab, azathioprine, or mycophenolate, and newer agents like satralizumab may be used in appropriately selected patients. Prognosis varies; MOGAD tends to have a different relapse pattern and sometimes a more favorable outcome than AQP4-IgG–positive NMOSD.

See also NMOSD, MOGAD, aquaporin-4.