A newly published study in the journal Multiple Sclerosis and Related Disorders has revealed no evidence of aquaporin-4 (AQP4) seropositivity or AQP4 serum titer levels in predicting the disease course of neuromyelitis optica spectrum disorder (NMOSD). 

Neuromyelitis optica spectrum disorder (NMOSD) is an uncommon autoimmune inflammatory disease affecting the central nervous system. Disability accumulation mainly occurs during diagnosis, supporting the argument for prompt identification and treatment to improve long-term neurologic outcomes.

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“As it is unclear whether AQP4 serostatus and serum titers can predict disability accumulation in NMOSD, we explore the relationship between these two measures and neurologic outcomes in NMOSD. We also explore the relationship between timing of administration of plasmapheresis and clinical disease course,” the authors wrote.

The research team conducted a retrospective review of all enrolled patients diagnosed with NMOSD at the Duke University Hospital (DUH) between January 2000 and 2021. 

Study results revealed that most patients exhibited either no change (31.9%) or showed improvement (27.1%) in disability over time, contrary to the current views on the NMOSD disease course. Moreover, no significant association between the clinical prognosis and initial AQP4 seropositivity (P= .830), initial AQP4 serum titer levels (P= .338), or administration of plasmapheresis (P= .1149) was reported. Additionally, no evidence was found on whether the AQP4 seropositivity or AQP4 serum titer levels predict the disease course of NMOSD. 

“Our results also failed to support an association between clinical prognosis and AQP4 seropositivity or AQP4 serum titer levels, highlighting the importance of exploring and identifying other possible clinical/paraclinical predictors of disease progression,” the authors highlighted.

The authors reported several limitations in their study, including the study’s small sample size and retrospective design, thereby emphasizing the need for multi-center studies and the development of multi-center databases of NMOSD data for accurate results.

“We were unable to find evidence supporting a favorable effect of plasmapheresis administration on disease outcomes, but our study may have lacked the power needed to pick up on such an association,” the authors concluded.

Prior studies on the disease course of NMOSD show substandard neurologic outcomes even in different cohorts treated with corticosteroids and immunosuppressive therapies, the researchers said. sHigh-dose intravenous glucocorticoids are the preferred treatment option for acute NMOSD. Although plasmapheresis is considered to be an important early therapy for acute attacks, further exploration is needed to assess the impact of plasmapheresis in acute NMOSD, the authors noted.

NMOSD is interrelated with the serum positivity of AQP4 antibodies, and the titer level may correspond with the severity of NMOSD symptomatology. No dependable predictors of acute NMOSD exacerbation have been identified, which may allow clinicians to increase therapy in patients with a greater risk of relapse.


Masha N, Kimbrough DJ, Eckstein CP, et.al. Neuromyelitis optica: clinical course and potential prognostic indicators. Mult Scler Relat Disord. Published online November 19, 2022.