Current state-of-art of the application of serum neurofilaments in multiple sclerosis diagnosis and monitoring

ABSTRACT

Introduction

Neurodegenerative processes occur from the beginning of multiple sclerosis, contribute to irreversible clinical disability and are only partially addressed by current disease-modifying therapies. Reliable quantification of neuro-axonal damage may contribute to improve the assessment of disease activity and progression, the definition of patients’ prognosis and treatment monitoring. Neurofilaments are neuron-specific cytoskeletal components that are released after neuro-axonal damage. Among them, neurofilament light chains represent a promising biomarker of neuro-axonal damage in multiple sclerosis.

Areas covered

This review summarizes the current state-of-art of neurofilament light chain quantification in multiple sclerosis, starting from their quantification in the cerebrospinal fluid to the most recent and sensitive techniques for their assessment in the blood. Their associations with clinical activity, disability, and MRI measures and their prognostic role during the different phases of the diseases are also discussed. Finally, their promise as biomarker of treatment effect and response is also examined.

Expert opinion

Serum neurofilaments light chain quantification is technically feasible and is likely to provide relevant pieces of information to understand MS pathophysiology, and identify patients at higher risk to develop multiple sclerosis and more severe disability. A future role in monitoring treatment effects and response and drug-related side-effects is envisaged.

KEYWORDS:

• Neurofilament
• neurofilament light chain
• multiple sclerosis
• biomarker
• treatment monitoring

Article highlights

• Neurofilaments are cytoskeletal components that are expressed only in neurons and that are released into the cerebrospinal fluid and then in the blood following neuro-axonal damage;

• Neurofilament light chain is the sub-unit of neurofilament most commonly investigated and its quantification is feasible not only in the cerebrospinal fluid, but also in the blood (serum or plasma);

• Neurofilament light chain levels are significantly increased in patients with multiple sclerosis, especially in the presence of clinical relapses or active MRI lesions, thus they are promising biomarkers for MS-related disease activity;

• Higher neurofilament light chain levels both in the cerebrospinal fluid and in the blood are significantly associated with a more severe disease, in terms of clinical disability, cognitive impairment, and MRI measures of damage (i.e., white matter lesions, microstructural abnormalities, and irreversible tissue loss);

• Higher neurofilament light chain levels are associated with a higher risk to develop multiple sclerosis in patients with clinically isolated syndrome and a more severe disease progression in patients with definite multiple sclerosis;

• Neurofilament light chain levels are high in untreated patients, whereas they are significantly decreased by many disease-modifying therapies, especially those highly effective, thus their quantification represents a promising biomarker for treatment monitoring.

Reviewer disclosures

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

Declaration of interest

P Preziosa received speaker honoraria from Biogen Idec, Novartis and ExceMED. MA Rocca received speaker honoraria from Biogen Idec, Novartis, Genzyme, Teva, Merck Serono, Roche, Celgene, and Bayer and receives research support from the Italian Ministry of Health, MS Society of Canada and Fondazione Italiana Sclerosi Multipla. M Filippi is Editor-in-Chief of the Journal of Neurology; received compensation for consulting services and/or speaking activities from Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.