What lies beneath grey matter atrophy in multiple sclerosis?

Abstract

This scientific commentary refers to ‘Cortical atrophy patterns in multiple sclerosis are non-random and clinically relevant’, by Steenwijk et al. (doi:10.1093/brain/awv337). Over the last 20 years, there have been remarkable advances in our understanding of pathogenic mechanisms in multiple sclerosis, particularly those responsible for relapses and remissions. Over the same period a series of increasingly effective treatments have become available that suppress relapses. However, there has been a conspicuous lack of success in treating progressive multiple sclerosis, which most people with the condition eventually develop, and which is associated with the greatest disability. This has led to a reappraisal of pathological processes underlying progressive multiple sclerosis, and the recognition that pathology is more extensive and complicated than formerly thought. In this issue of Brain , Steenwijk and co-workers look specifically at cortical atrophy in patients with long-standing multiple sclerosis, and reveal that such atrophy occurs in largely non-random patterns (Steenwijk et al. , 2016). Previously, a commonly held view of multiple sclerosis was of a multi-focal and multi-phasic immune-mediated white matter inflammatory demyelinating disorder, and indeed the suppression of such a process has underpinned the major progress in disease-modifying treatment to date. However, it is now abundantly clear that in progressive multiple sclerosis, demyelinating lesions may be as extensive in grey matter as they are in white matter, and that there is substantial and widespread neuro-axonal loss, not only in white matter lesions but also in normal-appearing white matter, and in both the cortical and deep grey matter. It is also clear that grey matter pathology is present in early relapsing-remitting multiple sclerosis and increases with time. Neuro-axonal loss is now thought to be responsible for a major proportion of irreversible progressive disability in multiple sclerosis, but its causes are poorly understood, …