• Written By: Michael Vaphiades, DO
    Neuro-Ophthalmology/Orbit

    This study found that there could be a distinct physiopathology for patients with aquaporin-4 (AQP4)-anitbody-negative neuromyelitis optica (NMO).

    They tested serum samples using indirect immunofluorescence and cell-based assays (CBAs) from 87 patients included in the French NOMADMUS database with a definite diagnosis of NMO and compared them with 54 controls with classic multiple sclerosis.

    They identified the CBA on live cells transfected with the untagged AQP4-M23 isoform as the best method to detect NMO. This had a sensitivity of 74.4 percent and a specificity of 100 percent.

    Compared to the classic indirect immunofluorescence or current AQP4-M1 CBA, they demonstrated a direct relationship between improvement of the sensitivity of the detection method and the distinctiveness and characteristics of the AQP4-antibody–negative NMO group. With the former, they found only slight differences between the two populations, whereas using the AQP4-M23 CBA, NMO patients who were AQP4-antibody–negative were characterized by an equal male/female ratio (P < 0.001), Caucasian ethnicity (P = 0.029) and an overrepresentation of simultaneous optic neuritis and transverse myelitis at first episode (P = 0.015). They experienced better visual acuity at last follow-up compared with seropositive NMO (P = 0.007).

    The authors conclude that the optimized AQP4-M23 CBA is the best detection method, increasing the sensitivity without specificity loss, and that improvement of assay sensitivity resulted in a more precise identification and characterization of the AQP4-antibody–negative NMO group.

    They also note that identification of specific demographic and disease-related features for AQP4-Ab–seronegative as compared with seropositive NMO patients raises the question of a different mechanism, not directly related to AQP4, that mediates the pathophysiology in such patients.