Background: Diagnosis of multiple sclerosis (MS) is established on criteria according to clinical and radiological manifestation. Cerebrospinal fluid (CSF) analysis is an important part of differential diagnosis of MS and other inflammatory processes in the central nervous system (CNS). Methods: In total, 242 CSF samples were collected from patients undergoing differential MS diagnosis because of the presence of T2-hyperintensive lesions on brain MRI. The non-MS patients were subdivided into systemic inflammatory diseases with CNS involvement (SID) or cerebrovascular diseases (CVD) or other non-inflammatory diseases (NID). All samples were analyzed for the presence of oligoclonal bands and ELISA was performed for detection of: INF gamma, IL-6, neurofilaments light chain (NF-L), GFAP, CHI3L1, CXCL13, and osteopontin. Results: The level of IL-6 (p = 0.024), osteopontin (p = 0.0002), and NF-L (p = 0.002) was significantly different among groups. IL-6 (p = 0.0350) and NF-L (p = 0.0015) level was significantly higher in SID compared to NID patients. A significantly higher level of osteopontin (p = 0.00026) and NF-L (p = 0.002) in MS compared to NID population was noted. ROC analysis found weak diagnostic power for osteopontin and NFL-L. Conclusions: The classical and non-standard markers of inflammatory process and neurodegeneration do not allow for sufficient differentiation between MS and non-MS inflammatory CNS disorders. Weak diagnostic power observed for the osteopontin and NF-L needs to be further investigated.

Various molecular biomarkers have been suggested as a method to improve the predictive value of prognosis in multiple sclerosis (MS). The characterization of such biomarkers would greatly enhance individual patient management. The aim of this study was to conduct a long-term, prospective evaluation of the prognostic value of molecular biomarkers in serum and cerebrospinal fluid (CSF) in patients in the early stages of MS, before the first treatment initiation. The study included a total of 121 MS patients. Serum and CSF were obtained during diagnostic process. Concentrations of IFN γ, IL-6, CHI3L1, osteopontin, CXCL13, GFAP and neurofilament light chains (NfLs) were analyzed. The mean time of the observation of clinical and radiological MS activity was 60 months after start of MS treatment. Higher serum concentrations of NfLs (Z = 2.28; p = 0.02) and CXCL13 (Z = 2.14; p = 0.03) correlated with need to change the first MS therapy (88% due to ineffectiveness and 12% due to adverse events). Higher NfLs concentrations in the CSF specifically correlated with the occurrence of radiological activity (Z = 2.02; p = 0.04). Increased NfLs and IL-6 concentrations in the CSF correlated with disability progression assessed with the EDSS (Z = 2.81; Z = 2.87; p = 0.004; p = 0.003, respectively), as well as with clinical and/or radiological disease activity (Z = 2.80; Z = 2.43; p = 0.004; p = 0.014, respectively). High levels of NfLs and Il6 in the CSF of MS patients assessed before the therapy may be an indication to use a highly effective therapy as the first treatment for MS.