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First published online March 15, 2018

Serum neurofilament light chain is a biomarker of acute and chronic neuronal damage in early multiple sclerosis

Abstract

Background:

Monitoring neuronal injury remains one key challenge in early relapsing-remitting multiple sclerosis (RRMS) patients. Upon axonal damage, neurofilament – a major component of the neuro-axonal cytoskeleton – is released into the cerebrospinal fluid (CSF) and subsequently peripheral blood.

Objective:

To investigate the relevance of serum neurofilament light chain (sNfL) for acute and chronic axonal damage in early RRMS.

Methods:

sNfL levels were determined in 74 patients (63 therapy-naive) with recently diagnosed clinically isolated syndrome (CIS) or RRMS using Single Molecule Array technology. Standardized 3 T magnetic resonance imaging (MRI) was performed at baseline and 1–3 consecutive follow-ups (42 patients; range: 6–37 months).

Results:

Baseline sNfL correlated significantly with T2 lesion volume (r = 0.555, p < 0.0001). There was no correlation between baseline sNfL and age, Expanded Disability Status Scale (EDSS) score or other calculated MRI measures. However, T2 lesion volume increased (r = 0.67, p < 0.0001) and brain parenchymal volume decreased more rapidly in patients with higher baseline sNfL (r = −0.623, p = 0.0004). Gd-enhancing lesions correlated positively with sNfL levels. Initiation of disease-modifying treatment led to a significant decrease in sNfL levels.

Conclusion:

sNfL indicates acute inflammation as demonstrated by correlation with Gd+ lesions. It is a promising biomarker for neuro-axonal damage in early multiple sclerosis (MS) patients, since higher baseline sNfL levels predicted future brain atrophy within 2 years.

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Published In

Article first published online: March 15, 2018
Issue published: April 2019

Keywords

  1. Multiple sclerosis
  2. neurodegeneration
  3. neurofilament
  4. biomarker
  5. clinical progression
  6. MRI
  7. disease activity

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© The Author(s), 2018.
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PubMed: 29542376

Authors

Affiliations

Nelly Siller
Department of Neurology and Focus Program Translational Neuroscience (FTN), Research Center for Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
Jens Kuhle
Neurologic Clinic and Policlinic and Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland
Muthuraman Muthuraman
Department of Neurology and Focus Program Translational Neuroscience (FTN), Research Center for Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
Christian Barro
Neurologic Clinic and Policlinic and Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland
Timo Uphaus
Department of Neurology and Focus Program Translational Neuroscience (FTN), Research Center for Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
Sergiu Groppa
Department of Neurology and Focus Program Translational Neuroscience (FTN), Research Center for Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
Ludwig Kappos
Neurologic Clinic and Policlinic and Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland
Frauke Zipp
Department of Neurology and Focus Program Translational Neuroscience (FTN), Research Center for Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
Stefan Bittner
Department of Neurology and Focus Program Translational Neuroscience (FTN), Research Center for Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany

Notes

Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany. [email protected]

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