Journal
NEUROLOGY
Volume 94, Issue 23, Pages E2457-E2467Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0000000000009571
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Funding
- national programme for quality registries in health care administered by Sveriges Kommuner och Landsting (Swedish Municipality and County Council)
- Socialstyrelsen (Swedish National Board of Health and Welfare)
- Biogen (IMSE natalizumab and dimethyl fumarate)
- Genzyme (IMSE teriflunomide and alemtuzumab)
- Novartis (IMSE fingolimod)
- Swedish Research Council
- Swedish Research Council for Health, Working Live and Welfare
- AFA foundation
- Swedish Brain Foundation
- Knut and Alice Wallenberg Foundation
- Swedish Research Council for Health, Working Life and Welfare
- Margaretha af Ugglas Foundation
- EU [733161]
- Biogen
- Novartis
- Sanofi
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ObjectiveTo investigate the association between plasma neurofilament light chain (pNfL) levels and the risk of developing sustained disability worsening.MethodsConcentrations of pNfL were determined in 4,385 persons with multiple sclerosis (MS) and 1,026 randomly selected population-based sex- and age-matched controls using the highly sensitive Single Molecule Array (SimoaTM) NF-Light Advantage Kit. We assessed the impact of age-stratified pNfL levels above the 80th, 95th, and 99th percentiles among controls on the risk of Expanded Disability Status Scale (EDSS) worsening within the following year and reaching sustained EDSS scores of 3.0, 4.0, and 6.0 and conversion to secondary progressive multiple sclerosis (SPMS).ResultsThe median (interquartile range [IQR]) pNfL was 7.5 (4.1) pg/mL in controls and 11.4 (9.6) pg/mL in MS (p < 0.001). The median (IQR) duration of follow-up was 5 (5.1) years. High pNfL was associated with increased adjusted rates of EDSS worsening ranging between 1.4 (95% confidence intervals [CIs]: 1.1-1.8) and 1.7 (95% CI: 1.4-2.3). High pNfL was also associated with the risk of reaching a sustained EDSS score of 3.0, with adjusted rates ranging between 1.5 (95% CI: 1.2-1.8) and 1.55 (95% CI: 1.3-1.8) over all percentile cutoffs (all p < 0.001). Similar increases were observed for the risk of sustained EDSS score 4.0. In contrast, the risk of reaching sustained EDSS score 6.0 and conversion to SPMS was not consistently significant.ConclusionsElevated pNfL levels at early stages of MS are associated with an increased risk of reaching sustained disability worsening. Hence, pNfL may serve as a prognostic tool to assess the risk of developing permanent disability in MS.
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