Serum neurofilament light chain as a presymptomatic biomarker in multiple sclerosis
ECTRIMS Online Library. Bjornevik K. Sep 13, 2019; 279546; 284
Kjetil Bjornevik
Kjetil Bjornevik
Contributions
Abstract

Abstract: 284

Type: Scientific Session

Abstract Category: Clinical aspects of MS - Epidemiology

K. Bjornevik1, K.L. Munger1, M. Cortese1, C. Barro2, B.C. Healy3, D.W. Niebuhr4, A.I. Scher4, J. Kuhle2, A. Ascherio1,5

1Harvard T.H. Chan School of Public Health, Boston, MA, United States, 2University Hospital Basel, University of Basel, Basel, Switzerland, 3Brigham and Women's Hospital, Boston, MA, 4Uniformed Services University of the Health Sciences, Bethesda, MD, 5Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States

Introduction: The clinical onset of multiple sclerosis (MS) is often preceded by unrecognized demyelinating events. Identification of these events at the time of occurrence would have implications for early diagnosis and treatment, as well as the search of causal factors for the disease.
Objectives: To assess whether concentrations of serum neurofilament light chain (sNfL), a biomarker of neuroaxonal damage, are elevated before the clinical onset of MS, and whether changes in sNfL contribute to identifying individuals with prodromal MS.
Methods: We conducted a nested case-control study among active-duty US military personnel who have serum samples stored in the Department of Defense Serum Repository. We selected 60 MS cases, either with two serum samples both collected before MS onset or with one sample collected before and one after MS onset. For each case, we selected one control matched by age, sex, race/ethnicity, and dates of sample collection. sNfL concentrations were measured using an ultrasensitive single-molecule array (Simoa) assay, and we compared the levels in cases and controls using conditional logistic regression and linear mixed effects models.
Results:
The levels of sNfL were higher in MS cases compared to their matched controls in serum samples drawn six years (median) before the clinical onset (p = 0.043). This difference increased with decreasing time to the case clinical onset (p = 0.002). A within-person increase in presymptomatic sNfL levels was associated with a higher risk of MS (rate ratio [RR] for ≥ 5 pg/mL increase: 7.50, 95% CI: 1.72 - 32.80). The clinical onset of MS was associated with a marked increase in sNfL levels (p = 0.009).
Conclusions: The levels of sNfL were increased six years before the clinical onset of MS. This indicates that MS has a prodromal phase lasting several years and that neuroaxonal damage occurs already during this phase.
Disclosure: Dr. Kjetil Bjornevik: nothing to disclose.
Dr. Kassandra L. Munger: nothing to disclose.
Dr. Marianna Cortese: nothing to disclose.
Dr. Christian Barro has received travel support from Teva and Novartis.
Dr. Brian C. Healy has received research support from Verily Life Sciences, Novartis, Merck Serono and Genzyme.
Dr. David W. Niebuhr: nothing to disclose.
Dr. Ann I. Scher: nothing to disclose.
Dr. Jens Kuhle has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Scientific advisory boards for Novartis Pharmaceuticals, Merck, Biogen, Sanofi Genzyme, Roche and Bayer. Funding for travel and/or speaker honoraria from Biogen, Sanofi Genzyme, Novartis, Merck Serono, Roche, Teva and the Swiss MS Society
Dr. Alberto Ascherio: nothing to disclose.

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