Body fluid markers for multiple sclerosis and differential diagnosis from atypical demyelinating disorders

ABSTRACT

Introduction

Body fluid markers could be helpful to predict the conversion into clinically definite multiple sclerosis (MS) in people with a first demyelinating event of the central nervous system (CNS). Consequently, biomarkers such as oligoclonal bands, which are integrated in the current MS diagnostic criteria, could assist early MS diagnosis.

Areas covered

This review examines existing knowledge on a broad spectrum of body fluid markers in people with a first CNS demyelinating event, explores their potential to predict conversion to MS, to assess MS disease activity, as well as their utility to differentiate MS from atypical demyelinating disorders such as neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein associated disease.

Expert opinion

This field of research has shown a dramatic increase of evidence, especially in the last decade. Some biomarkers are already established in clinical routine (e.g. oligoclonal bands) while others are currently implemented (e.g. kappa free light chains) or considered as breakthroughs (e.g. neurofilament light). Determination of biomarkers poses challenges for continuous monitoring, especially if exclusively detectable in cerebrospinal fluid. A handful of biomarkers are measurable in blood which holds a significant potential.

KEYWORDS:

• Biomarker
• clinically isolated syndrome
• demyelinating disorder
• first demyelinating CNS event
• multiple sclerosis
• myelin oligodendrocyte glycoprotein associated disease
• neuromyelitis optica spectrum disorder
• oligoclonal bands

Article highlights

• Cerebrospinal fluid (CSF) or blood biomarkers can assist early diagnosis of people with demyelinating disorders of the central nervous system (CNS) and can be used to predict conversion to multiple sclerosis (MS).

• Epstein-Barr virus infection was recently shown to be a strong environmental risk factor for developing MS.

• There are several CSF biomarkers showing promising prognostic ability in people with a first CNS demyelinating event to predict conversion to MS, including IgG oligoclonal bands, kappa free light chains, C-X-C motif chemokine ligand 13 or chitinase-3 like protein 1.

• Neurofilament light as a marker of neuroaxonal damage shows comparable values in blood and CSF enabling its use for disease activity monitoring in clinical routine.

• The development of more sensitive assays, the implementation of standardized study protocols and recruitment of large cohorts of people with a first CNS demyelinating event will facilitate biomarker development to better predict conversion to MS.

• Autoantibodies against aquaporin-4 and myelin oligodendrocyte glycoprotein are helpful for the differential diagnosis of MS.

Declaration of Interest

M Reindl was supported by a research grant from Roche. H Hegen has participated in meetings sponsored by, received speaker honoraria or travel funding from Bayer, Biogen, Bristol-Myers Squibb, Merck, Novartis, Sanofi-Genzyme, Siemens, Teva, and received honoraria for acting as consultant for Biogen, Bristol-Myers Squibb, Novartis, Roche and Teva. H Hegen is associate editor of Frontiers in Neurology. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.