Active primary progressive multiple sclerosis (PPMS) has effective treatment options, thus recognizing the disease’s bad prognosis early is crucial. As fast clinical decline is likely even in the absence of MRI activity, more sensitive indicators of continuing disease are required. Prediction of disability progression in relapsing-remitting MS was shown using Cerebrospinal fluid (CSF) chemokine CXCL-13, chitinase-3-like protein 1 (CHI3L1), and neurofilament light chains (NFL), however these markers have not been investigated in depth in PPMS. In this study, researchers wanted to assess the predictive value of cerebrospinal fluid (CSF) biomarkers representing microglial activation (CHI3L1), neuroaxonal damage (NFL), and central nervous system (CNS) B cell recruitment (CXCL-13). From 2013 to 2021, the clinic took in 45 PPMS patients (29 of which were female), whose ages ranged of 53 years (range 34,5 to 72,9 years). Patients had a standard CSF examination with oligoclonal bands (OCB) and quantitative IgG synthesis performed at the time of diagnosis; their spastic paraparesis had been present for a median of 3 years (range, 0.5-30 years). About 43  patients had at least 1 accessible EDSS score after follow-up (median follow-up 1.1, range 0.3-6.6 years). Quantification of CXCL-13, CHI3L1, and NFL was performed using immunoassays (Quantikine ELISA, R&D; UmanDiagnostics AB). Associations between CSF biomarkers and disability progression were analyzed using the Spearman’s rho test. About 80% or more of the patients exhibited typical brain MRI lesions on MRI, and 26 of 32 patients also had spinal cord lesions, however Gd enhancement was only found in a small percentage of the patients. About 93% of patients had OCB found in their CSF, and 19 individuals demonstrated EDSS improvement over time.Intrathecal CXCL-13 production was shown to correlate with CSF cell count (ρ= 0.615, P<0.001) and IgG index (ρ=0.557, P<0.001), but only moderately with follow-up ARMSS score (ρ=0.366, P=0.04). There was a moderate connection between CSF CHI3L1 and NFL levels at 1 year (ρ=0.325, P=0.04), although CHI3L1, but not NFL, was substantially greater in patients with EDSS progression (173 ng/ml vs. 229 ng/ml, P=0.005). Although there was no correlation between NFL and the amount of MRI lesions present at diagnosis, NFL did correlate adversely with illness duration (ρ=-0.426, P<0.01). Early handicap progression in PPMS patients seems to be predicted by CHI3L1 more so than by NFL or CXCL-13. More research in a larger prospective cohort is needed to fully assess its predictive value.


Reference: ECTRIMS 2022