Elevated CSF neurofilament proteins predict brain atrophy: A 15-year follow-up study

Mult Scler. 2016 Aug;22(9):1154-62. doi: 10.1177/1352458516645206. Epub 2016 May 11.


Background: Body fluid and structural imaging biomarkers give information on neurodegeneration. The relationship over time is not known in multiple sclerosis.

Objective: To investigate the temporal relationship of elevated cerebrospinal fluid (CSF) neurofilament (Nf) protein levels, a biomarker for axonal loss, with magnetic resonance imaging (MRI) atrophy measures.

Methods: In patients with multiple sclerosis, CSF Nf heavy chain (NfH) phosphoform levels were quantified at baseline and dichotomised into 'normal' and 'high'. Atrophy was assessed by MRI at baseline and 15-year follow-up using SIENAX and FreeSurfer software.

Results: High baseline CSF NfH(SMI35) levels predicted pronounced atrophy at 15-year follow-up (odds ratio (OR): 36, p < 0.01), in the absence of baseline brain atrophy (OR: 28, p < 0.05), for the averaged MRI normalised brain volume (1.44 L vs 1.33 L, p < 0.05), normalised grey matter volume (0.77 L vs 0.69 L, p < 0.01) and putamen (12.7 mL vs 10.7 mL, p < 0.05). Region-specific calculations including the spinal cord showed that a power of >80% is reached with 14-50 patients.

Conclusion: These data suggest that high CSF NfH levels are an early predictor of later brain and spinal cord atrophy using structural imaging biomarkers and can be investigated in reasonably sized patient cohorts.

Keywords: CSF; Neurodegeneration; biomarker; cerebrospinal fluid; multiple sclerosis; neurofilaments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Atrophy
  • Biomarkers / cerebrospinal fluid
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Brain / pathology
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Image Interpretation, Computer-Assisted
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multiple Sclerosis, Chronic Progressive / cerebrospinal fluid*
  • Multiple Sclerosis, Chronic Progressive / diagnostic imaging
  • Multiple Sclerosis, Chronic Progressive / pathology
  • Multiple Sclerosis, Relapsing-Remitting / cerebrospinal fluid*
  • Multiple Sclerosis, Relapsing-Remitting / diagnostic imaging
  • Multiple Sclerosis, Relapsing-Remitting / pathology
  • Neurofilament Proteins / cerebrospinal fluid*
  • Predictive Value of Tests
  • Software
  • Spinal Cord / diagnostic imaging
  • Spinal Cord / metabolism
  • Spinal Cord / pathology
  • Time Factors
  • Up-Regulation


  • Biomarkers
  • Neurofilament Proteins
  • neurofilament protein H