Cerebrospinal fluid levels of neurofilament and tau correlate with brain atrophy in natalizumab-treated multiple sclerosis

Eur J Neurol. 2017 Jan;24(1):112-121. doi: 10.1111/ene.13162. Epub 2016 Oct 4.


Background and purpose: Brain atrophy is related to clinical deterioration in multiple sclerosis (MS) but its association with intrathecal markers of inflammation or neurodegeneration is unclear. Our aim was to investigate whether cerebrospinal fluid (CSF) markers of inflammation or neurodegeneration are associated with brain volume change in natalizumab-treated MS and whether this change is reflected in non-lesional white matter metabolites.

Methods: About 25 patients with natalizumab-treated MS were followed for 3 years with assessment of percentage brain volume change (PBVC) and absolute quantification of metabolites with proton magnetic resonance spectroscopy (1 H MRS). Analyses of inflammatory [interleukin 1β (IL-1β), IL-6, C-X-C motif chemokine 8 (CXCL8), CXCL10, CXCL11, C-C motif chemokine 22] and neurodegenerative [neurofilament light protein (NFL), glial fibrillary acidic protein, myelin basic protein, tau proteins] markers were done at baseline and 1-year follow-up.

Results: The mean decline in PBVC was 3% at the 3-year follow-up, although mean 1 H MRS metabolite levels in non-lesional white matter were unchanged. CSF levels of NFL and tau at baseline correlated negatively with PBVC over 3 years (r = -0.564, P = 0.012, and r = -0.592, P = 0.010, respectively).

Conclusions: A significant 3-year whole-brain atrophy was not reflected in mean metabolite change of non-lesional white matter. In addition, our results suggest that CSF levels of NFL and tau correlate with brain atrophy development and may be used for evaluating treatment response in inflammatory active MS.

Keywords: brain atrophy; magnetic resonance spectroscopy; multiple sclerosis; natalizumab; neurofilament; quantitative magnetic resonance imaging; tau.

MeSH terms

  • Adult
  • Atrophy / cerebrospinal fluid
  • Atrophy / diagnostic imaging
  • Atrophy / pathology
  • Axons / pathology
  • Biomarkers / cerebrospinal fluid
  • Brain / diagnostic imaging
  • Brain / pathology*
  • Female
  • Humans
  • Immunologic Factors / therapeutic use*
  • Intermediate Filaments*
  • Magnetic Resonance Spectroscopy
  • Male
  • Middle Aged
  • Multiple Sclerosis / cerebrospinal fluid
  • Multiple Sclerosis / diagnostic imaging
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / pathology
  • Natalizumab / therapeutic use*
  • Treatment Outcome
  • Young Adult
  • tau Proteins / cerebrospinal fluid*


  • Biomarkers
  • Immunologic Factors
  • Natalizumab
  • tau Proteins