Neuromyelitis Optica spectrum disorder (NMOSD) is an immune-mediated disease that causes optic neuritis (ON), myelitis, brainstem, area postrema, diencephalic and/or cerebral syndromes. In NMOSD, antibodies bind to the extracellular domain of the Aquaporin-4 (AQP4) receptors, mostly found in astrocytes, and trigger cell- and complement–mediated cascades of cellular damage.

75% of patients with NMOSD have been found to have anti-AQP4 antibodies; however, there are some patients that don’t have them but still have clinical manifestations of the disease. These seronegative patients are often excluded from new therapeutic studies.

Eculizumab was approved by the FDA in 2019 for the treatment of seropositive NMOSD. This monoclonal antibody aims to decrease astrocyte loss by binding to and inhibiting C5, a terminal complement protein that participates in the pro-inflammatory cascade and membrane attack complex. It has proven to decrease the frequency of relapses in these patients.

A 42 year-old female debuted with bilateral ON. She was then found to have demyelinating lesions in her brainstem, cervical and thoracic cord. Seronegative NMOSD diagnosis was made since AQP4 antibodies were negative in multiple opportunities, but the patient met clinical and radiologic criteria for the disease. Attempted therapies included pulsed steroids, Tocilizumab, maintenance plasma exchange therapy, Mycophenolate mofetil, and Rituximab but she continued to have recurrence of optic neuritis. Once Eculizumab was started, the patient became stable and had a more prolonged remission time. Due to insurance authorization issues, Eculizumab was interrupted, and the patient relapsed again.

If patients with seronegative NMOSD are also thought to have oligodendrocyte and myelin damage after the disruption of astrocytes, therapies aiming to prevent astrocyte dysfunction should work on this population as evidenced by the patient whose case we report.

There is a need to include these patients in clinical studies to avoid treatment delays and further accumulation of disability.