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Neurofilaments in progressive multiple sclerosis: a systematic review

BACKGROUND: Neurofilament proteins have been extensively studied in relapsing–remitting multiple sclerosis, where they are promising biomarkers of disease activity and treatment response. Their role in progressive multiple sclerosis, where there is a particularly urgent need for improved biomarkers,...

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Autores principales: Williams, Thomas, Zetterberg, Henrik, Chataway, Jeremy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357650/
https://www.ncbi.nlm.nih.gov/pubmed/32447549
http://dx.doi.org/10.1007/s00415-020-09917-x
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author Williams, Thomas
Zetterberg, Henrik
Chataway, Jeremy
author_facet Williams, Thomas
Zetterberg, Henrik
Chataway, Jeremy
author_sort Williams, Thomas
collection PubMed
description BACKGROUND: Neurofilament proteins have been extensively studied in relapsing–remitting multiple sclerosis, where they are promising biomarkers of disease activity and treatment response. Their role in progressive multiple sclerosis, where there is a particularly urgent need for improved biomarkers, is less clear. The objectives of this systematic review are to summarise the literature on neurofilament light and heavy in progressive multiple sclerosis, addressing key questions. METHODS: A systematic search of PubMed, Embase, Web of Science and Scopus identified 355 potential sources. 76 relevant sources were qualitatively reviewed using QUADAS-2 criteria, and 17 were identified as at low risk of bias. We summarise the findings from all relevant sources, and separately from the 17 high-quality studies. RESULTS: Differences in neurofilament light between relapsing–remitting and progressive multiple sclerosis appear to be explained by differences in covariates. Neurofilament light is consistently associated with current inflammatory activity and future brain atrophy in progressive multiple sclerosis, and is consistently shown to be a marker of treatment response with immunosuppressive disease-modifying therapies. Associations with current or future disability are inconsistent, and there is no evidence of NFL being a responsive marker of purportedly neuroprotective treatments. Evidence on neurofilament heavy is more limited and inconsistent. CONCLUSIONS: Neurofilament light has shown consistent utility as a biomarker of neuroinflammation, future brain atrophy and immunosuppressive treatment response at a group level. Neither neurofilament light or heavy has shown a consistent treatment response to neuroprotective disease-modifying therapies, which will require further data from successful randomised controlled trials. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00415-020-09917-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-83576502021-08-30 Neurofilaments in progressive multiple sclerosis: a systematic review Williams, Thomas Zetterberg, Henrik Chataway, Jeremy J Neurol Review BACKGROUND: Neurofilament proteins have been extensively studied in relapsing–remitting multiple sclerosis, where they are promising biomarkers of disease activity and treatment response. Their role in progressive multiple sclerosis, where there is a particularly urgent need for improved biomarkers, is less clear. The objectives of this systematic review are to summarise the literature on neurofilament light and heavy in progressive multiple sclerosis, addressing key questions. METHODS: A systematic search of PubMed, Embase, Web of Science and Scopus identified 355 potential sources. 76 relevant sources were qualitatively reviewed using QUADAS-2 criteria, and 17 were identified as at low risk of bias. We summarise the findings from all relevant sources, and separately from the 17 high-quality studies. RESULTS: Differences in neurofilament light between relapsing–remitting and progressive multiple sclerosis appear to be explained by differences in covariates. Neurofilament light is consistently associated with current inflammatory activity and future brain atrophy in progressive multiple sclerosis, and is consistently shown to be a marker of treatment response with immunosuppressive disease-modifying therapies. Associations with current or future disability are inconsistent, and there is no evidence of NFL being a responsive marker of purportedly neuroprotective treatments. Evidence on neurofilament heavy is more limited and inconsistent. CONCLUSIONS: Neurofilament light has shown consistent utility as a biomarker of neuroinflammation, future brain atrophy and immunosuppressive treatment response at a group level. Neither neurofilament light or heavy has shown a consistent treatment response to neuroprotective disease-modifying therapies, which will require further data from successful randomised controlled trials. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00415-020-09917-x) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2020-05-23 2021 /pmc/articles/PMC8357650/ /pubmed/32447549 http://dx.doi.org/10.1007/s00415-020-09917-x Text en © The Author(s) 2020 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Review
Williams, Thomas
Zetterberg, Henrik
Chataway, Jeremy
Neurofilaments in progressive multiple sclerosis: a systematic review
title Neurofilaments in progressive multiple sclerosis: a systematic review
title_full Neurofilaments in progressive multiple sclerosis: a systematic review
title_fullStr Neurofilaments in progressive multiple sclerosis: a systematic review
title_full_unstemmed Neurofilaments in progressive multiple sclerosis: a systematic review
title_short Neurofilaments in progressive multiple sclerosis: a systematic review
title_sort neurofilaments in progressive multiple sclerosis: a systematic review
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357650/
https://www.ncbi.nlm.nih.gov/pubmed/32447549
http://dx.doi.org/10.1007/s00415-020-09917-x
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