Biomarkers in Blood and Cerebrospinal Fluid for Monitoring and Differentiating Demyelinating Inflammatory Central Nervous System Disorders

Abstract

Inflammatory demyelinating disorders of the central nervous system (CNS) are characterized by immune-mediated myelin injury and neuroaxonal damage. This thesis focused on multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD), which share clinical features but differ in immunopathology, prognosis, and treatment response. The aim was to evaluate soluble cerebrospinal fluid (CSF) and serum biomarkers reflecting neuroaxonal and astrocytic injury, blood–brain barrier dysfunction, and innate immune activation across these disorders.The first two studies investigated serum neurofilament light (sNfL) concentrations in patients with relapsing-remitting MS (RRMS). In a prospective cohort (Paper I) of clinically stable patients switching from standard to extended-interval natalizumab dosing (n = 45), sNfL concentrations remained stable over 12 months, supportingmaintained therapeutic efficacy without evidence of increased axonal injury. In a second prospective study (Paper II) including patients with active disease (n = 44), repeated sNfL measurements demonstrated moderate sensitivity and specificity for detecting inflammatory disease activity at the individual level, supporting its role as a complementary monitoring tool. In Paper III, soluble biomarker data from patients with NMOSD and MOGAD were retrospectively retrieved from medical records. CSF glial fibrillary acidic protein (GFAP), particularly when combined with albumin quotient, robustly discriminated AQP4-IgG-positive NMOSD from the combined MS, seronegative NMOSD, and MOGAD groups. In Paper IV, a newly developed method for quantifying the intermediate filament protein alpha-internexin in CSF was applied, demonstrating elevated concentrations in MS and a strong correlation with NfL, supporting its role as a marker of axonal injury. In Paper V, elevated serumcalprotectin distinguished NMOSD and MOGAD from RRMS, indicating distinct patterns of innate immune activation across these disorders. In conclusion, biomarker profiles differ across inflammatory demyelinating disorders and reflect disease-specific pathobiology. Integrated biomarker assessment may improve diagnostic precision and individualized monitoring of disease activity