Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 Jun 1;38(3):188-196.
doi: 10.1097/WCO.0000000000001369. Epub 2025 Apr 8.

Re-defining progression in multiple sclerosis

Jeffrey Lambe  1 , Daniel Ontaneda
Affiliations
Review

Re-defining progression in multiple sclerosis

Jeffrey Lambe et al. Curr Opin Neurol. .

Abstract

Purpose of review: The purpose of this article is to provide an overview of progression in multiple sclerosis (MS), including definitions, pathological mechanisms, and evidence that progressive biology begins early in the disease course.

Recent findings: Definitions of MS clinical course have been refined to acknowledge the presence of both relapse and progression biology throughout the disease. Progression independent of relapse activity represents a significant proportion of disability worsening in relapsing-remitting MS (RRMS) disease. Progression in MS appears to be caused by the complex interplay of multiple processes, including nonresolving inflammation, microglial activation, oxidative stress, mitochondrial dysfunction, energetic failure, and neuro-axonal degeneration. These processes appear to begin in the earliest disease stages and their contribution to clinical phenotypes is dynamic over time. Promising results from clinical trials of tolebrutinib, in particular, underline the utility of targeting both innate and adaptive immune mechanisms to reduce disability accumulation.

Summary: Pathological processes that underpin MS progression are detectable early in RRMS, evolve throughout the disease course and correlate with disability accumulation. Progression in MS should not be defined dichotomously - the focus instead should be on recognizing progressive components based on clinical measures and biomarkers early in the disease to better individualize treatment strategies.

Keywords: clinical trials; multiple sclerosis; neurodegeneration; neuroinflammation; progression.

PubMed Disclaimer

References

    1. Scalfari A, Neuhaus A, Daumer M, et al. Onset of secondary progressive phase and long-term evolution of multiple sclerosis. J Neurol Neurosurg Psychiatry 2014; 85:67–75.
    1. Antel J, Antel S, Caramanos Z, et al. Primary progressive multiple sclerosis: part of the MS disease spectrum or separate disease entity? Acta Neuropathol (Berl) 2012; 123:627–638.
    1. Dutta R, Trapp BD. Relapsing and progressive forms of multiple sclerosis: insights from pathology. Curr Opin Neurol 2014; 27:271–278.
    1. Lublin FD, Reingold SC. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Defining the clinical course of multiple sclerosis: results of an international survey. Neurology 1996; 46:907–911.
    1. Lublin FD, Reingold SC, Cohen JA, et al. Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology 2014; 83:278–286.

MeSH terms