Temporal association of sNfL and gad‐enhancing lesions in multiple sclerosis

Objective Multiple sclerosis (MS) is an autoimmune demyelinating disorder, which is characterized by relapses and remissions. Serum neurofilament light chain (sNfL) is an emerging biomarker of disease activity but its clinical use is still limited. In this study, we aim to characterize the temporal...

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Bibliographic Details
Published in:Annals of clinical and translational neurology Vol. 7; no. 6; pp. 945 - 955
Main Authors: Rosso, Mattia, Gonzalez, Cindy T., Healy, Brian C., Saxena, Shrishti, Paul, Anu, Bjornevik, Kjetil, Kuhle, Jens, Benkert, Pascal, Leppert, David, Guttmann, Charles, Bakshi, Rohit, Weiner, Howard L., Chitnis, Tanuja
Format: Journal Article
Language:English
Published: United States John Wiley & Sons, Inc 01.06.2020
John Wiley and Sons Inc
Wiley
Subjects:
Adult
Biological Assay
Biomarkers
Biomarkers - blood
Brain - diagnostic imaging
Brain - pathology
Consent
Female
Gadolinium
Humans
Image Enhancement
Interferon
Lesions
Longitudinal Studies
Magnetic Resonance Imaging
Male
Multiple sclerosis
Multiple Sclerosis - blood
Multiple Sclerosis - diagnosis
Multiple Sclerosis - pathology
Neurofilament Proteins - blood
Optic Nerve - diagnostic imaging
Optic Nerve - pathology
Patients
Recurrence
Severity of Illness Index
Spinal cord
Spinal Cord - diagnostic imaging
Spinal Cord - pathology
Studies
Time Factors
ISSN:2328-9503, 2328-9503
Online Access:Get full text
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Summary:Objective Multiple sclerosis (MS) is an autoimmune demyelinating disorder, which is characterized by relapses and remissions. Serum neurofilament light chain (sNfL) is an emerging biomarker of disease activity but its clinical use is still limited. In this study, we aim to characterize the temporal association between sNfL and new clinical relapses and new gadolinium‐enhancing (Gd+) lesions. Methods Annual sNfL levels were measured with a single‐molecule array (SIMOA) assay in 94 patients with MS enrolled in the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women’s Hospital (CLIMB) study. We used a multivariable linear mixed‐effects model to test the temporal association of sNfL with clinical relapses and/or new Gd+ lesions. We adjusted this model for age, disease duration, sex, and disease‐modifying therapies (DMTs) use. Results In the 3 months after a Gd+ lesion, we observed an average 35% elevation in sNfL (P < 0.0001) compared to remission samples. We also observed an average 32.3% elevation in sNfL at the time of or prior to a Gd+ lesion (P = 0.002) compared to remission. We observed a significant elevation in sNfL after a clinical relapse only when associated with a Gd+ lesion. Interpretation Our findings support sNfL as a marker of clinical relapses and Gd+ lesions. sNfL peaks in a 3‐month window around Gd+ lesions. sNfL shows promise as a biomarker of neurological inflammation and possibly of simultaneous Gd+ lesions during a clinical relapse.
Bibliography:This study was funded in part by the U.S. Department of Defense (W81XWH‐18‐1‐0648 to TC), Novartis, the Swiss National Research Foundation (320030_160221). We thank Merck Serono and the Nancy Davis Center Without Walls for their support of the CLIMB study.
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ISSN:2328-9503
2328-9503
DOI:10.1002/acn3.51060