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      Neurofilaments and 10-year follow-up in multiple sclerosis

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          Abstract

          The role of biomarkers to predict clinical outcome in multiple sclerosis (MS) is still debated.

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          Long‐term evolution of multiple sclerosis disability in the treatment era

          , Bruce A C Cree, Pierre-Antoine Gourraud … (2016)
          Objective To characterize the accrual of long‐term disability in a cohort of actively treated multiple sclerosis (MS) patients and to assess whether clinical and magnetic resonance imaging (MRI) data used in clinical trials have long‐term prognostic value. Methods This is a prospective study of 517 actively managed MS patients enrolled at a single center. Results More than 91% of patients were retained, with data ascertained up to 10 years after the baseline visit. At this last assessment, neurologic disability as measured by the Expanded Disability Status Scale (EDSS) was stable or improved compared to baseline in 41% of patients. Subjects with no evidence of disease activity (NEDA) by clinical and MRI criteria during the first 2 years had long‐term outcomes that were no different from those of the cohort as a whole. 25‐OH vitamin D serum levels were inversely associated with short‐term MS disease activity; however, these levels had no association with long‐term disability. At a median time of 16.8 years after disease onset, 10.7% (95% confidence interval [CI] = 7.2–14%) of patients reached an EDSS ≥ 6, and 18.1% (95% CI = 13.5–22.5%) evolved from relapsing MS to secondary progressive MS (SPMS). Interpretation Rates of worsening and evolution to SPMS were substantially lower when compared to earlier natural history studies. Notably, the NEDA 2‐year endpoint was not a predictor of long‐term stability. Finally, the data call into question the utility of annual MRI assessments as a treat‐to‐target approach for MS care. Ann Neurol 2016;80:499–510
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            Brain atrophy and disability progression in multiple sclerosis patients: a 10-year follow-up study.

            Cecilie Jacobsen, Jesper Hagemeier, Kjell-Morten Myhr … (2014)
            To identify MRI biomarkers associated with long-term disability progression in patients with multiple sclerosis (MS), and to define the rate of evolution of global, tissue-specific and regional atrophy in patients with MS over long-term.
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              Neurofilament light chain predicts disease activity in relapsing-remitting MS

              Kristin N Varhaug, Christian Barro, Kjetil Bjørnevik … (2017)
              Objective: To investigate whether serum neurofilament light chain (NF-L) and chitinase 3-like 1 (CHI3L1) predict disease activity in relapsing-remitting MS (RRMS). Methods: A cohort of 85 patients with RRMS were followed for 2 years (6 months without disease-modifying treatment and 18 months with interferon-beta 1a [IFNB-1a]). Expanded Disability Status Scale was scored at baseline and every 6 months thereafter. MRI was performed at baseline and monthly for 9 months and then at months 12 and 24. Serum samples were collected at baseline and months 3, 6, 12, and 24. We analyzed the serum levels of NF-L using a single-molecule array assay and CHI3L1 by ELISA and estimated the association with clinical and MRI disease activity using mixed-effects models. Results: NF-L levels were significantly higher in patients with new T1 gadolinium-enhancing lesions (37.3 pg/mL, interquartile range [IQR] 25.9–52.4) and new T2 lesions (37.3 pg/mL, IQR 25.1–48.5) compared with those without (28.0 pg/mL, IQR 21.9–36.4, β = 1.258, p < 0.001 and 27.7 pg/mL, IQR 21.8–35.1, β = 1.251, p < 0.001, respectively). NF-L levels were associated with the presence of T1 gadolinium-enhanced lesions up to 2 months before (p < 0.001) and 1 month after (p = 0.009) the time of biomarker measurement. NF-L levels fell after initiation of IFNB-1a treatment (p < 0.001). Changes in CHI3L1 were not associated with clinical or MRI disease activity or interferon-beta 1a treatment. Conclusion: Serum NF-L could be a promising biomarker for subclinical MRI activity and treatment response in RRMS. In clinically stable patients, serum NF-L may offer an alternative to MRI monitoring for subclinical disease activity. ClinicalTrials.gov identifier: NCT00360906.
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                Author and article information

                Journal
                Title: Multiple Sclerosis Journal
                Abbreviated Title: Mult Scler
                Publisher: SAGE Publications
                ISSN (Print): 1352-4585
                ISSN (Electronic): 1477-0970
                Publication date Created: August 2018
                Publication date Created: September 2018
                Publication date (Electronic): August 2018
                Publication date (Print): September 2018
                Volume: 24
                Issue: 10
                Pages: 1301-1307
                Affiliations
                [1 ]Neuroscience Research Group, Department of Neurology, Stavanger University Hospital, Stavanger, Norway
                [2 ]Department of Neurology, Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway
                [3 ]Section of Biostatistics, Department of Research, Stavanger University Hospital, Stavanger, Norway
                [4 ]Neuroscience Research Group, Department of Neurology, Stavanger University Hospital, Stavanger, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway
                Article
                DOI: 10.1177/1352458518782005
                PubMed ID: 30066611
                SO-VID: fc4033de-cf21-436a-bef1-7ed5d4372cb5
                Copyright © © 2018
                License:

                http://journals.sagepub.com/page/policies/text-and-data-mining-license

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