Secondary Progression in Multiple Sclerosis: Neuronal Exhaustion or Distinct Pathology?. Issue 5 (May 2016)

• Record Type: Journal Article
• Authors: Larochelle, Catherine; Uphaus, Timo; Prat, Alexandre; Zipp, Frauke
• Is Part Of: Trends in neurosciences. Volume 39:Issue 5(2016)
• Page Start: 325
• Page End: 339
• Publication Date: 2016-05
• Subjects: conversion -- progression -- secondary progressive -- neurodegeneration -- senescence -- multiple sclerosis; Neurology -- Periodicals; Neurophysiology -- Periodicals; Neurobiology -- Periodicals; 612.8
• DOI: 10.1016/j.tins.2016.02.001
• Languages: English
• ISSNs: 0166-2236

Abstract

Abstract : Prevention of progression in neurological diseases, particularly in multiple sclerosis (MS) but also in neurodegenerative diseases, remains a significant challenge. MS patients switch from a relapsing-remitting to a progressive disease course, but it is not understood why and how this conversion occurs and why some patients never experience disease progression. Do aging and accumulation of neuronal damage induce progression, or do cognitive symptoms and accelerated grey matter (GM) atrophy point to distinct processes affecting networks? This review weighs accepted dogma against real data on the secondary progressive phase of the disease, highlighting current challenges in this important field and directions towards development of treatment strategies to slow or prevent progression of disability. Trends: MS is a devastating inflammatory disease of the CNS and one of the most frequent causes of irreversible disability in young people. Why the disease exhibits such different courses, relapsing-remitting at onset followed (or not) by a phase of increasing disability (SPMS), remains a mystery. If conversion occurs, disease resembles neurodegenerative disorders and so far is not satisfactorily amenable to treatment. Recent assumptions of underlying primary neurodegeneration do not explain distinct characteristics of SPMS such as accelerated GM atrophy, and call for unraveling the processes and risk factors underlying conversion. The influence of aging and lifestyle on the crosstalk of the immune and nervous systems, the impact of immunity on neuronal networks, and emerging local autoimmunity are pressing research objectives for CNS inflammatory and degenerative diseases.