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Determinants and Biomarkers of Progression Independent of Relapses in Multiple Sclerosis

Massimiliano Calabrese Orcid Logo, Paolo Preziosa Orcid Logo, Antonio Scalfari Orcid Logo, Elisa Colato, Damiano Marastoni, Martina Absinta, Marco Battaglini, Nicola De Stefano, Massimiliano Di Filippo Orcid Logo, Simon Hametner, Owain Howell Orcid Logo, Matilde Inglese, Hans Lassmann, Roland Martin, Richard Nicholas Orcid Logo, Richard Reynolds, Maria A. Rocca Orcid Logo, Agnese Tamanti, Marco Vercellino, Luisa Maria Villar Orcid Logo, Massimo Filippi Orcid Logo, Roberta Magliozzi Orcid Logo

Annals of Neurology, Volume: 96, Issue: 1, Pages: 1 - 20

Swansea University Author: Owain Howell Orcid Logo

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DOI (Published version): 10.1002/ana.26913

Abstract

Clinical, pathological, and imaging evidence in multiple sclerosis (MS) suggests that a smoldering inflammatory activity is present from the earliest stages of the disease and underlies the progression of disability, which proceeds relentlessly and independently of clinical and radiological relapses...

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Published in: Annals of Neurology
ISSN: 0364-5134 1531-8249
Published: Wiley 2024
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URI: https://cronfa.swan.ac.uk/Record/cronfa66032
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Abstract: Clinical, pathological, and imaging evidence in multiple sclerosis (MS) suggests that a smoldering inflammatory activity is present from the earliest stages of the disease and underlies the progression of disability, which proceeds relentlessly and independently of clinical and radiological relapses (PIRA). The complex system of pathological events driving “chronic” worsening is likely linked with the early accumulation of compartmentalized inflammation within the central nervous system as well as insufficient repair phenomena and mitochondrial failure. These mechanisms are partially lesion-independent and differ from those causing clinical relapses and the formation of new focal demyelinating lesions; they lead to neuroaxonal dysfunction and death, myelin loss, glia alterations, and finally, a neuronal network dysfunction outweighing central nervous system (CNS) compensatory mechanisms. This review aims to provide an overview of the state of the art of neuropathological, immunological, and imaging knowledge about the mechanisms underlying the smoldering disease activity, focusing on possible early biomarkers and their translation into clinical practice.
Item Description: Review
College: Faculty of Medicine, Health and Life Sciences
Issue: 1
Start Page: 1
End Page: 20