Neurofilament-light and contactin-1 association with long-term brain atrophy in natalizumab-treated relapsing-remitting multiple sclerosis

Mult Scler. 2022 Dec;28(14):2231-2242. doi: 10.1177/13524585221118676. Epub 2022 Sep 3.


Background: 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.

Objective: 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.

Methods: 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.

Results: 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, p = 0.013), VVC (standardized β = 0.36, p < 0.001), and TVC (standardized β = -0.24, p = 0.02). For sCNTN1, only 3-month level was associated with VVC (standardized β = -0.31, p = 0.002).

Conclusion: 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.

Keywords: MRI volumetrics; Multiple sclerosis; contactin-1; natalizumab; neurofilament-light.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Atrophy
  • Brain* / diagnostic imaging
  • Brain* / pathology
  • Contactin 1* / metabolism
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting* / diagnostic imaging
  • Multiple Sclerosis, Relapsing-Remitting* / drug therapy
  • Natalizumab / adverse effects


  • Natalizumab
  • CNTN1 protein, human
  • Contactin 1