biostudies-literaturevan Lierop ZYStichting MS Research2231-2242https://www.ebi.ac.uk/biostudies/studies/S-EPMC9679802biostudies-literatureUnknown28(14)<h4>Background</h4>Despite highly effective treatment strategies for patients with relapsing-remitting multiple sclerosis (RRMS), long-term neurodegeneration and disease progression are often considerable. Accurate blood-based biomarkers that predict long-term neurodegeneration are lacking.<h4>Objective</h4>To assess the predictive value of serum neurofilament-light (sNfL) and serum contactin-1 (sCNTN1) for long-term magnetic resonance imaging (MRI)-derived neurodegeneration in natalizumab-treated patients with RRMS.<h4>Methods</h4>sNfL and sCNTN1 were measured in an observational cohort of natalizumab-treated patients with RRMS at baseline (first dose) and at 3 months, Year 1, Year 2, and last follow-up (median = 5.2 years) of treatment. Disability progression was quantified using "EDSS-plus" criteria. Neurodegeneration was measured by calculating annualized percentage brain, ventricular, and thalamic volume change (PBVC, VVC, and TVC, respectively). Linear regression analysis was performed to identify longitudinal predictors of neurodegeneration.<h4>Results</h4>In total, 88 patients (age = 37 ± 9 years, 75% female) were included, of whom 48% progressed. Year 1 sNfL level (not baseline or 3 months) was associated with PBVC (standardized (std.) β = -0.26, <i>p</i> = 0.013), VVC (standardized β = 0.36, <i>p</i> < 0.001), and TVC (standardized β = -0.24, <i>p</i> = 0.02). For sCNTN1, only 3-month level was associated with VVC (standardized β = -0.31, <i>p</i> = 0.002).<h4>Conclusion</h4>Year 1 (but not baseline) sNfL level was predictive for long-term brain atrophy in patients treated with natalizumab. sCNTN1 level did not show a clear predictive value.Multiple sclerosis (Houndmills, Basingstoke, England)Neurofilament-light and contactin-1 association with long-term brain atrophy in natalizumab-treated relapsing-remitting multiple sclerosis.PMC967980218-358fvan Dam MToorop AANoteboom SMoraal BKillestein Jvan Lierop ZYSteenwijk MDBarkhof Fvan Kempen ZLUitdehaag BMSchoonheim MMTeunissen CEfalseNeurofilament-light and contactin-1 association with long-term brain atrophy in natalizumab-treated relapsing-remitting multiple sclerosis.<h4>Background</h4>Despite highly effective treatment strategies for patients with relapsing-remitting multiple sclerosis (RRMS), long-term neurodegeneration and disease progression are often considerable. Accurate blood-based biomarkers that predict long-term neurodegeneration are lacking.<h4>Objective</h4>To assess the predictive value of serum neurofilament-light (sNfL) and serum contactin-1 (sCNTN1) for long-term magnetic resonance imaging (MRI)-derived neurodegeneration in natalizumab-treated patients with RRMS.<h4>Methods</h4>sNfL and sCNTN1 were measured in an observational cohort of natalizumab-treated patients with RRMS at baseline (first dose) and at 3 months, Year 1, Year 2, and last follow-up (median = 5.2 years) of treatment. Disability progression was quantified using "EDSS-plus" criteria. Neurodegeneration was measured by calculating annualized percentage brain, ventricular, and thalamic volume change (PBVC, VVC, and TVC, respectively). Linear regression analysis was performed to identify longitudinal predictors of neurodegeneration.<h4>Results</h4>In total, 88 patients (age = 37 ± 9 years, 75% female) were included, of whom 48% progressed. Year 1 sNfL level (not baseline or 3 months) was associated with PBVC (standardized (std.) β = -0.26, <i>p</i> = 0.013), VVC (standardized β = 0.36, <i>p</i> < 0.001), and TVC (standardized β = -0.24, <i>p</i> = 0.02). For sCNTN1, only 3-month level was associated with VVC (standardized β = -0.31, <i>p</i> = 0.002).<h4>Conclusion</h4>Year 1 (but not baseline) sNfL level was predictive for long-term brain atrophy in patients treated with natalizumab. sCNTN1 level did not show a clear predictive value.2022-01-01T00:00:00Z2022 Dec2025-04-18T17:07:33.042Z2025-04-07T04:41:03.106ZS-EPMC96798023606249210.1177/13524585221118676