Determinants and biomarkers of progression independent of relapses in multiple sclerosis
Author(s)
Type
Journal Article
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. ANN NEUROL 2024;96:1–20
Date Issued
2024-07-01
Date Acceptance
2024-02-15
Citation
Annals of Neurology, 2024, 96 (1)
ISSN
0364-5134
Publisher
Wiley
Journal / Book Title
Annals of Neurology
Volume
96
Issue
1
Copyright Statement
© 2024 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/38568026
Subjects
B-CELL FOLLICLES
CEREBROSPINAL-FLUID
Clinical Neurology
CLINICALLY ISOLATED SYNDROME
DISABILITY PROGRESSION
GREY-MATTER DEMYELINATION
IRON RIM LESIONS
Life Sciences & Biomedicine
MENINGEAL INFLAMMATION
NEUROFILAMENT LIGHT
Neurosciences
Neurosciences & Neurology
Science & Technology
SPINAL-CORD LESIONS
T-CELLS
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2024-06-19