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Cerebrospinal fluid neurofilament light chain in multiple sclerosis and its subtypes: a meta-analysis of case–control studies
  1. Sarah-Jane Martin1,2,
  2. Sarah McGlasson3,4,
  3. David Hunt3,4,
  4. James Overell2,5
  1. 1 Anne Rowling Centre for Regenerative Neurology, University of Edinburgh, Edinburgh, UK
  2. 2 University of Glasgow, Glasgow, UK
  3. 3 MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
  4. 4 Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK
  5. 5 Glasgow Multiple Sclerosis Clinical Research Centre, Queen Elizabeth University Hospital, Glasgow, UK
  1. Correspondence to Dr Sarah-Jane Martin, Glasgow Multiple Sclerosis Clinical Research Centre, Institute of Neurological Sciences, Queen Elizabeth University Hospital, Glasgow, UK; sarah-jane.martin{at}


Objective Neurofilament is a biomarker of axonal injury proposed as a useful adjunct in the monitoring of patients with multiple sclerosis (MS). We conducted a systematic review and meta-analysis of case–control studies that have measured neurofilament light chain (NfL) levels in cerebrospinal fluid (CSF) of people with MS (pwMS), in order to determine whether, and to what degree, CSF NfL levels differentiate MS from controls, or the subtypes or stages of MS from each other.

Methods Guidelines on Preferred Reporting Items for Systematic Reviews and Meta-Analyses were followed. Electronic databases were searched for published and ‘grey’ literature, with 151 hits. Of 51 full articles screened, 20 were included in qualitative analysis, and 14 in meta-analysis.

Results CSF NfL was higher in 746 pwMS than 435 (healthy and disease) controls, with a moderate effect size of 0.61 (p < 0.00001). Mean CSF NfL levels were significantly higher in 176 pwMS with relapsing disease than 92 with progressive disease (2124.8 ng/L, SD 3348.9 vs 1121.4 ng/L, SD 947.7, p = 0.0108). CSF NfL in 138 pwMS in relapse (irrespective of MS subtype) was double that seen in 268 pwMS in remission (3080.6 ng/L, SD 4715.9 vs 1541.7 ng/L, SD 2406.5, p < 0.0001).

Conclusions CSF NfL correlates with MS activity throughout the course of MS, reflecting the axonal damage in pwMS. Relapse is more strongly associated with elevated CSF NfL levels than the development of progression, and NfL may be most useful as a marker of disease ‘activity’ rather than as a marker of disability or disease stage.

  • multiple sclerosis
  • CSF
  • neuroimmunology

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  • Contributors MSJ, study concept and design, acquisition and interpretation of data. SM, critical revision of manuscript. DH, critical revision of manuscript. JO, study design, interpretation of data and critical revision of manuscript.

  • Funding Dr Martin is funded by a CSO PME grant as part of a PhD from the Rowling Scholar Scheme. Dr Hunt is funded by a Wellcome Trust fellowship. There are no competing interests for any authors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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