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July 2020; 7 (4) ArticleOpen Access

Serum neurofilament light chain is a useful biomarker in pediatric multiple sclerosis

View ORCID ProfileMarie-Christine Reinert, View ORCID ProfilePascal Benkert, View ORCID ProfileJens Wuerfel, Zuzanna Michalak, Esther Ruberte, View ORCID ProfileChristian Barro, Peter Huppke, Wiebke Stark, Harald Kropshofer, Davorka Tomic, David Leppert, Jens Kuhle, Wolfgang Brück, Jutta Gärtner
First published May 13, 2020, DOI: https://doi.org/10.1212/NXI.0000000000000749
Marie-Christine Reinert
From the Department of Pediatrics and Adolescent Medicine (M.-C.R., P.H., W.S., J.G.), Division of Pediatric Neurology, University Medical Centre Göttingen, Georg August University Göttingen, Germany; Clinical Trial Unit (P.B.), Department of Clinical Research, University Hospital Basel, University of Basel; Medical Image Analysis Centre Basel (MIAC AG) (J.W., E.R.); Department of Biomedical Engineering (J.W.), University Basel; Neurologic Clinic and Policlinic (Z.M., C.B., D.L., J.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel; Novartis Pharma AG (H.K., D.T.), Basel, Switzerland; and Institute of Neuropathology (W.B.), University Medical Centre Göttingen, Georg August University Göttingen, Germany.
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Pascal Benkert
From the Department of Pediatrics and Adolescent Medicine (M.-C.R., P.H., W.S., J.G.), Division of Pediatric Neurology, University Medical Centre Göttingen, Georg August University Göttingen, Germany; Clinical Trial Unit (P.B.), Department of Clinical Research, University Hospital Basel, University of Basel; Medical Image Analysis Centre Basel (MIAC AG) (J.W., E.R.); Department of Biomedical Engineering (J.W.), University Basel; Neurologic Clinic and Policlinic (Z.M., C.B., D.L., J.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel; Novartis Pharma AG (H.K., D.T.), Basel, Switzerland; and Institute of Neuropathology (W.B.), University Medical Centre Göttingen, Georg August University Göttingen, Germany.
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Jens Wuerfel
From the Department of Pediatrics and Adolescent Medicine (M.-C.R., P.H., W.S., J.G.), Division of Pediatric Neurology, University Medical Centre Göttingen, Georg August University Göttingen, Germany; Clinical Trial Unit (P.B.), Department of Clinical Research, University Hospital Basel, University of Basel; Medical Image Analysis Centre Basel (MIAC AG) (J.W., E.R.); Department of Biomedical Engineering (J.W.), University Basel; Neurologic Clinic and Policlinic (Z.M., C.B., D.L., J.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel; Novartis Pharma AG (H.K., D.T.), Basel, Switzerland; and Institute of Neuropathology (W.B.), University Medical Centre Göttingen, Georg August University Göttingen, Germany.
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Zuzanna Michalak
From the Department of Pediatrics and Adolescent Medicine (M.-C.R., P.H., W.S., J.G.), Division of Pediatric Neurology, University Medical Centre Göttingen, Georg August University Göttingen, Germany; Clinical Trial Unit (P.B.), Department of Clinical Research, University Hospital Basel, University of Basel; Medical Image Analysis Centre Basel (MIAC AG) (J.W., E.R.); Department of Biomedical Engineering (J.W.), University Basel; Neurologic Clinic and Policlinic (Z.M., C.B., D.L., J.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel; Novartis Pharma AG (H.K., D.T.), Basel, Switzerland; and Institute of Neuropathology (W.B.), University Medical Centre Göttingen, Georg August University Göttingen, Germany.
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Esther Ruberte
From the Department of Pediatrics and Adolescent Medicine (M.-C.R., P.H., W.S., J.G.), Division of Pediatric Neurology, University Medical Centre Göttingen, Georg August University Göttingen, Germany; Clinical Trial Unit (P.B.), Department of Clinical Research, University Hospital Basel, University of Basel; Medical Image Analysis Centre Basel (MIAC AG) (J.W., E.R.); Department of Biomedical Engineering (J.W.), University Basel; Neurologic Clinic and Policlinic (Z.M., C.B., D.L., J.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel; Novartis Pharma AG (H.K., D.T.), Basel, Switzerland; and Institute of Neuropathology (W.B.), University Medical Centre Göttingen, Georg August University Göttingen, Germany.
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Christian Barro
From the Department of Pediatrics and Adolescent Medicine (M.-C.R., P.H., W.S., J.G.), Division of Pediatric Neurology, University Medical Centre Göttingen, Georg August University Göttingen, Germany; Clinical Trial Unit (P.B.), Department of Clinical Research, University Hospital Basel, University of Basel; Medical Image Analysis Centre Basel (MIAC AG) (J.W., E.R.); Department of Biomedical Engineering (J.W.), University Basel; Neurologic Clinic and Policlinic (Z.M., C.B., D.L., J.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel; Novartis Pharma AG (H.K., D.T.), Basel, Switzerland; and Institute of Neuropathology (W.B.), University Medical Centre Göttingen, Georg August University Göttingen, Germany.
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Peter Huppke
From the Department of Pediatrics and Adolescent Medicine (M.-C.R., P.H., W.S., J.G.), Division of Pediatric Neurology, University Medical Centre Göttingen, Georg August University Göttingen, Germany; Clinical Trial Unit (P.B.), Department of Clinical Research, University Hospital Basel, University of Basel; Medical Image Analysis Centre Basel (MIAC AG) (J.W., E.R.); Department of Biomedical Engineering (J.W.), University Basel; Neurologic Clinic and Policlinic (Z.M., C.B., D.L., J.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel; Novartis Pharma AG (H.K., D.T.), Basel, Switzerland; and Institute of Neuropathology (W.B.), University Medical Centre Göttingen, Georg August University Göttingen, Germany.
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Wiebke Stark
From the Department of Pediatrics and Adolescent Medicine (M.-C.R., P.H., W.S., J.G.), Division of Pediatric Neurology, University Medical Centre Göttingen, Georg August University Göttingen, Germany; Clinical Trial Unit (P.B.), Department of Clinical Research, University Hospital Basel, University of Basel; Medical Image Analysis Centre Basel (MIAC AG) (J.W., E.R.); Department of Biomedical Engineering (J.W.), University Basel; Neurologic Clinic and Policlinic (Z.M., C.B., D.L., J.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel; Novartis Pharma AG (H.K., D.T.), Basel, Switzerland; and Institute of Neuropathology (W.B.), University Medical Centre Göttingen, Georg August University Göttingen, Germany.
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Harald Kropshofer
From the Department of Pediatrics and Adolescent Medicine (M.-C.R., P.H., W.S., J.G.), Division of Pediatric Neurology, University Medical Centre Göttingen, Georg August University Göttingen, Germany; Clinical Trial Unit (P.B.), Department of Clinical Research, University Hospital Basel, University of Basel; Medical Image Analysis Centre Basel (MIAC AG) (J.W., E.R.); Department of Biomedical Engineering (J.W.), University Basel; Neurologic Clinic and Policlinic (Z.M., C.B., D.L., J.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel; Novartis Pharma AG (H.K., D.T.), Basel, Switzerland; and Institute of Neuropathology (W.B.), University Medical Centre Göttingen, Georg August University Göttingen, Germany.
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Davorka Tomic
From the Department of Pediatrics and Adolescent Medicine (M.-C.R., P.H., W.S., J.G.), Division of Pediatric Neurology, University Medical Centre Göttingen, Georg August University Göttingen, Germany; Clinical Trial Unit (P.B.), Department of Clinical Research, University Hospital Basel, University of Basel; Medical Image Analysis Centre Basel (MIAC AG) (J.W., E.R.); Department of Biomedical Engineering (J.W.), University Basel; Neurologic Clinic and Policlinic (Z.M., C.B., D.L., J.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel; Novartis Pharma AG (H.K., D.T.), Basel, Switzerland; and Institute of Neuropathology (W.B.), University Medical Centre Göttingen, Georg August University Göttingen, Germany.
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David Leppert
From the Department of Pediatrics and Adolescent Medicine (M.-C.R., P.H., W.S., J.G.), Division of Pediatric Neurology, University Medical Centre Göttingen, Georg August University Göttingen, Germany; Clinical Trial Unit (P.B.), Department of Clinical Research, University Hospital Basel, University of Basel; Medical Image Analysis Centre Basel (MIAC AG) (J.W., E.R.); Department of Biomedical Engineering (J.W.), University Basel; Neurologic Clinic and Policlinic (Z.M., C.B., D.L., J.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel; Novartis Pharma AG (H.K., D.T.), Basel, Switzerland; and Institute of Neuropathology (W.B.), University Medical Centre Göttingen, Georg August University Göttingen, Germany.
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Jens Kuhle
From the Department of Pediatrics and Adolescent Medicine (M.-C.R., P.H., W.S., J.G.), Division of Pediatric Neurology, University Medical Centre Göttingen, Georg August University Göttingen, Germany; Clinical Trial Unit (P.B.), Department of Clinical Research, University Hospital Basel, University of Basel; Medical Image Analysis Centre Basel (MIAC AG) (J.W., E.R.); Department of Biomedical Engineering (J.W.), University Basel; Neurologic Clinic and Policlinic (Z.M., C.B., D.L., J.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel; Novartis Pharma AG (H.K., D.T.), Basel, Switzerland; and Institute of Neuropathology (W.B.), University Medical Centre Göttingen, Georg August University Göttingen, Germany.
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Wolfgang Brück
From the Department of Pediatrics and Adolescent Medicine (M.-C.R., P.H., W.S., J.G.), Division of Pediatric Neurology, University Medical Centre Göttingen, Georg August University Göttingen, Germany; Clinical Trial Unit (P.B.), Department of Clinical Research, University Hospital Basel, University of Basel; Medical Image Analysis Centre Basel (MIAC AG) (J.W., E.R.); Department of Biomedical Engineering (J.W.), University Basel; Neurologic Clinic and Policlinic (Z.M., C.B., D.L., J.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel; Novartis Pharma AG (H.K., D.T.), Basel, Switzerland; and Institute of Neuropathology (W.B.), University Medical Centre Göttingen, Georg August University Göttingen, Germany.
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Jutta Gärtner
From the Department of Pediatrics and Adolescent Medicine (M.-C.R., P.H., W.S., J.G.), Division of Pediatric Neurology, University Medical Centre Göttingen, Georg August University Göttingen, Germany; Clinical Trial Unit (P.B.), Department of Clinical Research, University Hospital Basel, University of Basel; Medical Image Analysis Centre Basel (MIAC AG) (J.W., E.R.); Department of Biomedical Engineering (J.W.), University Basel; Neurologic Clinic and Policlinic (Z.M., C.B., D.L., J.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel; Novartis Pharma AG (H.K., D.T.), Basel, Switzerland; and Institute of Neuropathology (W.B.), University Medical Centre Göttingen, Georg August University Göttingen, Germany.
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Citation
Serum neurofilament light chain is a useful biomarker in pediatric multiple sclerosis
Marie-Christine Reinert, Pascal Benkert, Jens Wuerfel, Zuzanna Michalak, Esther Ruberte, Christian Barro, Peter Huppke, Wiebke Stark, Harald Kropshofer, Davorka Tomic, David Leppert, Jens Kuhle, Wolfgang Brück, Jutta Gärtner
Neurol Neuroimmunol Neuroinflamm Jul 2020, 7 (4) e749; DOI: 10.1212/NXI.0000000000000749

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Abstract

Objective To investigate serum neurofilament light chain (sNfL) as a potential biomarker for disease activity and treatment response in pediatric patients with multiple sclerosis (MS).

Methods In this retrospective cohort study, sNfL levels were measured in a pediatric MS cohort (n = 55, follow-up 12–105 months) and in a non-neurologic pediatric control cohort (n = 301) using a high-sensitivity single-molecule array assay. Association of sNfL levels and treatment and clinical and MRI parameters were calculated.

Results Untreated patients had higher sNfL levels than controls (median 19.0 vs 4.6 pg/mL; CI [4.732, 6.911]), p < 0.001). sNfL levels were significantly associated with MRI activity (+9.1% per contrast-enhancing lesion, CI [1.045, 1.138], p < 0.001; +0.6% per T2-weighted lesion, CI [1.001, 1.010], p = 0.015). Higher values were associated with a relapse <90 days ago (+51.1%; CI [1.184, 1.929], p < 0.001) and a higher Expanded Disability Status Scale score (CI [1.001, 1.240], p = 0.048). In patients treated with interferon beta-1a/b (n = 27), sNfL levels declined from 14.7 to 7.9 pg/mL after 6 ± 2 months (CI [0.339, 0.603], p < 0.001). Patients with insufficient control of clinical or MRI disease activity under treatment with interferon beta-1a/b or glatiramer acetate who switched to fingolimod (n = 18) showed a reduction of sNfL levels from 16.5 to 10.0 pg/mL 6 ± 2 months after switch (CI [0.481, 0.701], p < 0.001).

Conclusions sNfL is a useful biomarker for monitoring disease activity and treatment response in pediatric MS. It is most likely helpful to predict disease severity and to guide treatment decisions in patients with pediatric MS. This study provides Class III evidence that sNfL levels are associated with disease activity in pediatric MS.

Glossary

CEL=
contrast-enhancing lesion;
CV=
coefficient of variation;
DMT=
disease-modifying therapy;
EDSS=
Expanded Disability Status Scale;
GA=
glatiramer acetate;
IFN=
interferon;
sNfL=
serum neurofilament light chain

Footnotes

  • Go to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article.

  • The Article Processing Charge was funded by Georg August University Göttingen.

  • Received August 20, 2019.
  • Accepted in final form April 9, 2020.
  • Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

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