UC Irvine

Abstract

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 hours before and after treatment. 

Results: In 14 RMS patients, IVMP produced significant decreases in GFAP, Serpin A9, FLRT2, contactin2, protogenin, MOG, CXCL9, CD6, BAFF (TNFSF13B), IL12B, and CDCP1. Composite MSDA scores showed paradoxical postIVMP increases in overall disease activity, neuroinflammation, immunomodulation, and neuroaxonal integrity, with decreased myelin biology scores. In a pooled nonRMS 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.