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Toscano et al. Neuroimmunol Neuroinflammation 2021;8:14-41 Neuroimmunology
DOI: 10.20517/2347-8659.2020.12 and Neuroinflammation

Review Open Access

CSF biomarkers in multiple sclerosis: beyond
neuroinflammation

Simona Toscano, Francesco Patti

Department “GF Ingrassia”, Section of Neurosciences, Multiple Sclerosis Center, University of Catania, Catania 95123, Italy.
Correspondence to: Prof. Francesco Patti, Department “GF Ingrassia”, Section of Neurosciences, Multiple Sclerosis Center,
University of Catania, Catania 95123, Italy. E-mail: patti@unict.it

How to cite this article: Toscano S, Patti F. CSF biomarkers in multiple sclerosis: beyond neuroinflammation. Neuroimmunol
Neuroinflammation 2021;8:14-41. http://dx.doi.org/10.20517/2347-8659.2020.12

Received: 31 Jan 2020 First Decision: 20 May 2020 Revised: 10 Jun 2020
Accepted: 28 Jun 2020 Fisrt online: 21 Aug 2020 Published: 21 Mar 2021

Academic Editor: Roberta Magliozzi Copy Editor: Cai-Hong Wang Production Editor: Jing Yu

Abstract
For many years, quantifiable biomarkers in neurological diseases have represented a hot topic. In multiple sclerosis
(MS), cerebrospinal fluid biomarkers have played a diagnostic role since the introduction of Poser’s criteria in
1983, with IgG oligoclonal bands playing a supporting role in an epoch prior to magnetic resonance imaging and
a complementary one after the introduction of McDonald criteria in 2001. Nowadays, that supporting role has
turned into a main one in substituting for dissemination in time and defining the diagnosis of MS in patients with
a first clinical event, according to the 2017 revised McDonald criteria. Possibly kappa free light chains, N-CAM,
chitinase 3-like protein 1 and IgM oligoclonal bands, not yet implemented in clinical practice, could similarly gain
importance in the near future. Furthermore, the increasing knowledge of molecular mechanisms leading to chronic
inflammation has enhanced interest in looking for biomarkers of disease activity, better defining the MS phenotype
and patients with highly active disease. Accordingly, myelin proteins, intermediate filaments, metalloproteinases
and other molecules involved in the inflammatory cascade, are currently under investigation. Finally, it has long
been known that axonal loss occurs from the early phases, leading to a progressive neurological deterioration.
Since established criteria to assess treatment failure and transition to progressive forms are still lacking, both
treatment response and prognostic biomarkers would be useful to predict MS course, and neurofilaments seem to
have this potential. The purpose of this review article was to illustrate biomarkers that have been already validated
or require further validation after proving to be useful in exploratory studies and potentially could prove useful in
clinical practice in the coming years.

Keywords: Multiple sclerosis, biomarkers, cerebrospinal fluid, neurofilaments, oligoclonal bands, disease activity

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
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