Utility of Multi-Analyte Protein Assay to Distinguish Multiple Sclerosis Clinical Relapse from Pseudoexacerbation

Multiple sclerosis (MS) is a chronic autoimmune condition associated with acute relapses. Distinguishing true inflammatory exacerbations from pseudoexacerbations is challenging. We hypothesized that a multi-analyte protein assay would accurately identify acute gadolinium-enhancing lesions and outperform a single biomarker. Sixty-six individuals with MS (33 with acute symptoms, 33 under routine surveillance) who had paired Octave Multiple Sclerosis Disease Activity (MSDA) and MRI results were studied. In symptomatic participants, MSDA testing preceded MRI in 79% of cases. Across both cohorts, a Disease Activity Score (DAS) ≥ 6.0–10.0 was highly sensitive and specific for predicting gadolinium-enhancing lesions. Elevated concentrations of myelin oligodendrocyte glycoprotein (p = 0.013) and neurofilament light (NfL) (p < 0.0001), and reduced B-cell activating factor levels (p < 0.0001), were observed in participants with gadolinium enhancement. The DAS predicted enhancement more accurately than NfL alone, (area under the curve = 98.1% vs. 82.8%; p = 0.0061). These findings suggest the MSDA test provides rapid, accurate disease activity assessments, improving clinical management.