ObjectiveTo test the hypothesis that the pattern of serum biomarkers of disease activity and disability in myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD) will be different from those in neuromyelitis optica spectrum disorder (NMOSD) with anti–aquaporin-4 antibodies (AQP4-Abs).MethodsUsing ultrasensitive single-molecule array assays, we measured neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and tau in the sera of consecutive patients with MOGAD (n = 16) and NMOSD with AQP4-Ab (n = 33). Serum biomarker levels were compared between patients in relapse and remission states, and correlations between the levels of these biomarkers and Expanded Disability Status Scale (EDSS) scores were analyzed within each group.ResultsIn the MOGAD group, the serum tau level was higher in a relapse state than in a remission state (relapse vs remission: 0.5 [0.4–0.5] vs 0.2 [0.1–0.3] pg/mL, p = 0.027). Both serum levels of NfL and tau correlated with the EDSS score (NfL: r = 0.684, p = 0.003; tau: r = 0.524, p = 0.045). Meanwhile, in the NMOSD group, serum NfL and GFAP levels were higher in a relapse state than in a remission state (relapse vs remission: NfL, 34.8 [12.2–62.3] vs 13.0 [11.3–20.0] pg/mL, p = 0.010; GFAP, 253.8 [150.6–303.0] vs 104.4 [93.9–127.9] pg/mL, p = 0.016). Only the serum GFAP level correlated with the EDSS score (r = 0.485, p = 0.012).ConclusionThe pattern of serum biomarkers of disease activity and disability in MOGAD showed a distinct feature from those in NMOSD with AQP4-Ab, which implicates different pathogeneses between the 2 diseases.

Background: Recently, several serum biomarkers have been proposed in Neuromyelitis Optica Spectrum Disorders (NMOSD) to monitor disease activity. Objective: The objective of the study is to evaluate the longitudinal clinical value of serum biomarkers in patients with NMOSD. Methods: We prospectively recruited consecutive NMOSD patients with anti-aquaporin-4 antibody and obtained serum samples at enrollment, after 6–12 months of follow-up (main period), and at attacks. Using single-molecule array assays, we evaluated longitudinal changes of serum neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and GFAP/NfL levels. Results: Overall, 64 patients (58 women) were enrolled (age: 51 years, disease duration: 6.7 years) and 133 samples were obtained. Among patients who did not develop new attacks during the main period ( n = 62), serum levels of NfL, GFAP, and GFAP/NfL were significantly decreased over time in patients with attacks (<2 months) at enrollment ( n = 14 (23%)), whereas serum NfL and GFAP levels gradually increased in the others ( n = 48 (77%)). During the study, five (8%) patients developed new attacks; only serum GFAP levels increased consistently upon these events compared with baseline levels. To differentiate attacks from remissions, serum GFAP levels showed the largest area under the receiver operating characteristic curve (0.876, 95% confidence interval: 0.801–0.951). Conclusion: Among NfL, GFAP, and GFAP/NfL, serum GFAP might be the most appropriate for monitoring NMOSD longitudinally, which warrants future confirming studies.

ObjectivesSerum synaptic proteins levels may change with age‐related neurodegeneration, affecting their clinical implications as a disease biomarker. We aimed to investigate neuronal and astroglial markers in patients with multiple sclerosis (MS) and aquaporin‐4 antibody‐seropositive neuromyelitis optica spectrum disorders (NMOSD) to compare the clinical implications of these markers according to age.MethodsUsing single‐molecule array assays, we measured neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) in sera from consecutive patients with MS (n = 117) and NMOSD (n = 63). For each disease, we assessed correlations between these markers and disease severity (Expanded Disability Status Scale [EDSS]) scores according to three age groups (≤44, 45–54, and ≥55 years).ResultsAlthough serum GFAP levels were significantly higher in patients with NMOSD than those with MS, levels of both serum markers revealed significant positive correlations with EDSS scores in both diseases. In MS patients, the degrees of correlation between serum NfL (or GFAP) levels and EDSS scores were similar across all age groups. However, in NMOSD patients, positive GFAP‐EDSS correlations were distinctively stronger in the youngest than in the oldest group. Conversely, there were no positive NfL‐EDSS correlations in NMOSD in the youngest group, but there were significant in the oldest group.InterpretationThe degrees to which serum NfL and GFAP levels reflect disease severity vary significantly with patient age in NMOSD, but not in MS. These findings suggest that the pathological processes and progression differ between the diseases; hence, serum biomarker levels may need to be interpreted differently according to patient age and disease type.