High serum neurofilament light chain normalizes after hematopoietic stem cell transplantation for MS
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Abstract
Objective To evaluate neurofilament light chain (NfL) levels in serum and CSF of patients with aggressive MS pre- and post-treatment with immunoablation followed by autologous hematopoietic stem cell transplantation (IAHSCT) and examine associations with clinical and MRI outcomes.
Methods Paired serum and CSF in addition to MRI and clinical measures were collected on 23 patients with MS at baseline and 1 and 3 years post-IAHSCT. An additional 33 sera and CSF pairs were taken from noninflammatory neurologic controls. NfL levels were quantitated using the Simoa platform (Quanterix).
Results Baseline MS NfL levels were significantly elevated relative to controls in serum (p = 0.001) and CSF (p = 0.001). Following IAHSCT, high pretreatment NfL levels significantly reduced in serum (p = 0.0023) and CSF (p = 0.0068) and were not significantly different from controls. Serum and CSF NfL levels highly correlated (r = 0.81, p < 0.0001). Baseline NfL levels were associated with worse pretreatment disease measures (Expanded Disability Status Scale [EDSS], relapses, MRI lesions, and MR spectroscopy (MRS) N-acetylaspartate/creatine). Elevated baseline NfL levels were associated with persistently worse indices of disease burden post-IAHSCT (sustained EDSS progression, cognition, quality of life, T1 and T2 lesion volumes, MRS, and brain atrophy).
Conclusion These data substantiate that serum and CSF NfL levels reflect disease severity and treatment response in patients with MS and may therefore be a useful biomarker. Baseline serum levels associated with markers of pretreatment disease severity and post-treatment outcomes.
Classification of evidence This study provides Class II evidence that for patients with aggressive MS, serum NfL levels are associated with disease severity.
Glossary
- DMT=
- disease-modifying treatment;
- EDSS=
- Expanded Disability Status Scale;
- FIS=
- Fatigue Impact Score;
- IAHSCT=
- immunoablation followed by autologous hematopoietic stem cell transplantation;
- MRS=
- MR spectroscopy;
- MSQOL=
- MS Quality of Life;
- NAA/Cr=
- N-acetylaspartate/creatine;
- NfL=
- neurofilament light chain;
- RRMS=
- relapsing-remitting MS;
- SPMS=
- secondary progressive MS;
- VOI=
- volume of interest
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 the authors.
Editorial, page e599
- Received January 11, 2019.
- Accepted in final form April 29, 2019.
- Copyright © 2019 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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