Regional Distribution and Evolution of Gray Matter Damage in Different Populations of Multiple Sclerosis Patients

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August 12, 2015 (PLOS One)

Gray-matter (GM) atrophy and lesions are present during the earliest stages of Multiple Sclerosis (MS) and are major contributors of disease progression and long-term clinical outcomes. It continues to remain unclear the relationship between specific (focal) and widespread (diffuse) GM damage. In this study, researchers investigate the “distribution and evolution” of cortical thinning and how that is influenced by local appearance of new GM lesions at various stages of MS and in various populations among MS patients.

In this retrospective study, 96 patients were included, followed and had at least a 5-year MRI follow-up to assess regional cortical thickness of GM lesions. Twenty had clinical isolated syndrome (CIS), 27 had early Relapsing Remitting MS (RRMS), 29 had late RRMS, and 20 had Secondary Progressive MS (SPMS).

Results of this 5-year period showed that new GM lesions appeared more often in areas such as in hippocampus and parahippocampal gyri, insula, cingulate cortex, superior frontal gyrus, and cerebellum. These areas were those that showed the greatest reduction in thickness and volume, thus presenting the greatest damage. Correlation between appearance of new cortical lesions and cortical thinning was more prevalent in CIS and early RRMS than in late RRMS and SPMS.

Some considerations are as follows:

It can be implied that at the early stages in MS, patients with the highest accumulation of new cortical lesions show the greatest cortical thinning, and then in later stages of disease, other factors may contribute to cortical atrophy. Second, cortical thinning in the areas mentioned above could be more dependent on “diffuse subpial cortical lesions” – the most frequently type if cortical lesions observed in ’post-mortem” MS brains but nearly invisible by MRI.  Third, there appears to be diffuse loss of neurons, axons, and synapses in non-demyelinated “normal” grey matter in addition to demyelination in cortical thinning. This observation may explain the GM atrophy that does not accompany lesions.

In light of this study’s results, disease-modifying drugs for MS should be given as early as possible to help prevent cortical atrophy and, ultimate, irreversible disability.

Read this full study here.