Progressive multiple sclerosis: from pathogenic mechanisms to treatment

456Citations
Citations of this article
1.2kReaders
Mendeley users who have this article in their library.

This article is free to access.

Abstract

During the past decades, better understanding of relapsing-remitting multiple sclerosis disease mechanisms have led to the development of several disease-modifying therapies, reducing relapse rates and severity, through immune system modulation or suppression. In contrast, current therapeutic options for progressive multiple sclerosis remain comparatively disappointing and challenging. One possible explanation is a lack of understanding of pathogenic mechanisms driving progressive multiple sclerosis. Furthermore, diagnosis is usually retrospective, based on history of gradual neurological worsening with or without occasional relapses, minor remissions or plateaus. In addition, imaging methods as well as biomarkers are not well established. Magnetic resonance imaging studies in progressive multiple sclerosis show decreased blood–brain barrier permeability, probably reflecting compartmentalization of inflammation behind a relatively intact blood–brain barrier. Interestingly, a spectrum of inflammatory cell types infiltrates the leptomeninges during subpial cortical demyelination. Indeed, recent magnetic resonance imaging studies show leptomeningeal contrast enhancement in subjects with progressive multiple sclerosis, possibly representing an in vivo marker of inflammation associated to subpial demyelination. Treatments for progressive disease depend on underlying mechanisms causing central nervous system damage. Immunity sheltered behind an intact blood–brain barrier, energy failure, and membrane channel dysfunction may be key processes in progressive disease. Interfering with these mechanisms may provide neuroprotection and prevent disability progression, while potentially restoring activity and conduction along damaged axons by repairing myelin. Although most previous clinical trials in progressive multiple sclerosis have yielded disappointing results, important lessons have been learnt, improving the design of novel ones. This review discusses mechanisms involved in progressive multiple sclerosis, correlations between histopathology and magnetic resonance imaging studies, along with possible new therapeutic approaches.

References Powered by Scopus

Cortical demyelination and diffuse white matter injury in multiple sclerosis

1463Citations
N/AReaders
Get full text

The relation between inflammation and neurodegeneration in multiple sclerosis brains

1144Citations
N/AReaders
Get full text

Placebo-controlled multicentre randomised trial of interferon β-1b in treatment of secondary progressive multiple sclerosis

986Citations
N/AReaders
Get full text

Cited by Powered by Scopus

Multiple Sclerosis: Mechanisms and Immunotherapy

641Citations
N/AReaders
Get full text

Blood-Brain Barrier Dysfunction Amplifies the Development of Neuroinflammation: Understanding of Cellular Events in Brain Microvascular Endothelial Cells for Prevention and Treatment of BBB Dysfunction

229Citations
N/AReaders
Get full text

Epidemiology and treatment of multiple sclerosis in elderly populations

220Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Correale, J., Gaitán, M. I., Ysrraelit, M. C., & Fiol, M. P. (2017, March 1). Progressive multiple sclerosis: from pathogenic mechanisms to treatment. Brain. Oxford University Press. https://doi.org/10.1093/brain/aww258

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 336

72%

Researcher 97

21%

Professor / Associate Prof. 24

5%

Lecturer / Post doc 10

2%

Readers' Discipline

Tooltip

Medicine and Dentistry 218

42%

Neuroscience 161

31%

Biochemistry, Genetics and Molecular Bi... 96

18%

Nursing and Health Professions 47

9%

Article Metrics

Tooltip
Mentions
Blog Mentions: 1

Save time finding and organizing research with Mendeley

Sign up for free