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Abstract
Objective: To investigate a potential effect of riluzole on serum neurofilaments (Nf) compared to placebo and the relationship between longitudinal clinical and MRI outcomes and serum Nf levels.
Methods: Serum samples were obtained from participants enrolled in a randomized double-blind trial of neuroprotection with riluzole vs placebo as an add-on to weekly interferon-β (IFN-β)–1a IM initiated 3 months after randomization. Nf measurements were performed by ELISA and electrochemiluminescence immunoassay.
Results: Longitudinal serum samples were available from 22 riluzole and 20 placebo participants over 24 months. There was no observed treatment effect with riluzole. Nf light chain (NfL) levels decreased over time (p = 0.007 at 24 months), whereas the Nf heavy chain was unchanged (p = 0.997). Changes in NfL were correlated with EDSS change (p = 0.009) and neuropsychological outcomes. Brain volume decreased more rapidly in patients with high baseline NfL (p = 0.05 at 12 months and p = 0.008 at 24 months) and this relationship became stronger at 24 months (p = 0.024 for interaction). Higher and increasing NfL predicted higher number of gadolinium-enhancing lesions (p < 0.001 for both).
Conclusions: Our findings support the potential value of serum NfL as a marker of neuroaxonal injury in early multiple sclerosis. Its reduction over time could represent regression to the mean, or a possible treatment effect of IFN-β-1a. The association with whole brain atrophy and the formation of acute white matter lesions has relevant implications to use serum NfL as a noninvasive biomarker of the overall consequences of brain damage and ongoing disease activity.
ClinicalTrials.gov identifier: NCT00501943.
GLOSSARY
- BVMT-R=
- Brief Visuospatial Memory Test–revised;
- CI=
- confidence interval;
- CV=
- coefficient of variation;
- CVLT-II=
- California Verbal Learning Test, second edition;
- ECL=
- electrochemiluminescence;
- EDSS=
- Expanded Disability Status Scale;
- IFN-β=
- interferon-β;
- MS=
- multiple sclerosis;
- MSFC=
- Multiple Sclerosis Functional Composite;
- Nf=
- neurofilament;
- NfL=
- neurofilament light chain;
- NfH=
- neurofilament heavy chain;
- PASAT=
- Paced Auditory Serial Addition Test;
- RRMS=
- relapsing-remitting multiple sclerosis
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Editorial, page 816
- Received May 2, 2016.
- Accepted in final form October 10, 2016.
- © 2017 American Academy of Neurology
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