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The multiple sclerosis prodrome

Abstract

A prodrome is an early set of signs, symptoms or other findings that occur before the onset of typical symptoms of a disease. Prodromal phases are well recognized in several neurological and inflammatory diseases, but the possibility of a prodrome in multiple sclerosis (MS) has received relatively little attention until the past few years. In this Perspective, we summarize what is currently known about the MS prodrome, including its possible duration, clinical features and potential biomarkers. We also consider what insights and lessons can be learned from knowledge of and research into the prodromal phases of other diseases. A better understanding of the MS prodrome could have profound clinical implications as it could enable earlier recognition of MS and earlier initiation of treatments that reduce relapse rates and long-term disability. Knowledge of the MS prodrome could also affect research into the causes of MS, and putative risk factors must be re-evaluated in light of the MS prodrome. We conclude by outlining the major knowledge gaps and propose future initiatives.

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Both authors contributed to all aspects of the manuscript.

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Correspondence to Helen Tremlett.

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Competing interests

N.M. is funded by NIH/NINDS (grant number K23NS101099) and the Charles H. Hood Foundation. H.T. is the Canada Research Chair for Neuroepidemiology and Multiple Sclerosis. Current research support has been received from the National Multiple Sclerosis Society, the Canadian Institutes of Health Research, the Multiple Sclerosis Society of Canada and the Multiple Sclerosis Scientific Research Foundation. In the past 5 years, she has received research support from the UK MS Trust and travel expenses to present at CME conferences from the Consortium of MS Centres (2018), the National MS Society (2016, 2018), ECTRIMS and ACTRIMS (2015, 2016, 2017, 2018, 2019, 2020), and the American Academy of Neurology (2015, 2016, 2019). Speaker honoraria are either declined or donated to an MS charity or to an unrestricted grant for use by H.T.’s research group.

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Nature Reviews Neurology thanks M. Amato, T. Chitnis, G. Disanto and R. Dobson for their contribution to the peer review of this work.

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Makhani, N., Tremlett, H. The multiple sclerosis prodrome. Nat Rev Neurol 17, 515–521 (2021). https://doi.org/10.1038/s41582-021-00519-3

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