Acute effects of high-dose corticosteroids on serum biomarker profiles in primary CNS demyelinating disease: A pilot study.

BACKGROUND: Acute inflammatory relapses in primary CNS demyelinating diseases, including relapsing multiple sclerosis (RMS), MOG-antibody-associated disease (MOGAD), and neuromyelitis optica spectrum disorder (NMOSD), drive hospitalization, disability, and socioeconomic burden. Blood-based biomarkers are increasingly used for relapse detection and treatment monitoring. OBJECTIVE: Investigate effects of corticosteroids on short-term dynamics of serum biomarkers. METHODS: We conducted a pilot prospective study of 22 patients with acute neuro-inflammatory conditions, assessing changes in an 18 protein serum biomarker panel (Octave MSDA) and composite disease scores before and after high-dose intravenous methylprednisolone (IVMP; 1000 mg/day for 3 days). Samples were collected within 24 h before and after treatment. RESULTS: In 14 RMS patients, IVMP produced significant decreases in GFAP, Serpin A9, FLRT2, contactin-2, protogenin, MOG, CXCL9, CD6, BAFF (TNFSF13B), IL-12B, and CDCP1. Composite MSDA scores showed paradoxical post-IVMP increases in overall disease activity, neuroinflammation, immunomodulation, and neuroaxonal integrity, with decreased myelin biology scores. In a pooled non-RMS group (MOGAD, NMOSD, idiopathic optic neuritis, and transverse myelitis), CNTN2 and IL-12B exhibited similar corticosteroid responsive reductions. CONCLUSIONS: These findings suggest that high-dose corticosteroids rapidly and significantly alter multiple serum biomarkers and composite activity scores across demyelinating conditions, underscoring implications for biomarker timing, interpretation, and future validation.