Brain atrophy in multiple sclerosis: mechanisms, clinical relevance and treatment options

Abstract

Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system characterized by focal or diffuse inflammation, demyelination, axonal loss and neurodegeneration. Brain atrophy can be seen in the earliest stages of MS, progresses faster compared to healthy adults, and is a reliable predictor of future physical and cognitive disability. In addition, it is widely accepted to be a valid, sensitive and reproducible measure of neurodegeneration in MS. Reducing the rate of brain atrophy has only recently been incorporated as a critical endpoint into the clinical trials of new or emerging disease modifying drugs (DMDs) in MS. With the advent of easily accessible neuroimaging softwares along with the accumulating evidence, clinicians may be able to use brain atrophy measures in their everyday clinical practice to monitor disease course and response to DMDs. In this review, we will describe the different mechanisms contributing to brain atrophy, their clinical relevance on disease presentation and course and the effect of current or emergent DMDs on brain atrophy and neuroprotection. which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Memantine for Multiple Sclerosis: A Systematic Review and Meta-Analysis of Randomized Trials

“…It is important to note that DMT initiation can be associated with paradoxical brain pseudo-atrophy which is understood to be due to fluid shifts and resolution of edema as neuroinflammation subsides ( 35 ). This is different from true brain atrophy which is a true marker of extensive demyelination, axonal loss, and degeneration ( 36 ). True brain atrophy, specifically thinning of the fronto-parietal cortical regions, precuneus atrophy ( 37 ), and thalamic atrophy ( 38 ) are significantly correlated with cognitive impairment.…”

Monitoring the Redox Status in Multiple Sclerosis

“…Main pathological findings of MS include the blood-brain barrier disruption, multifocal inflammation, demyelination, oligodendrocyte loss, reactive gliosis, and axonal degeneration [ 12 ]. Multifocal immune-mediated destruction of myelin and oligodendrocytes leading to progressive axonal loss is a main cause of neurological deficits in MS [ 13 , 14 , 15 ].…”

Approved and Emerging Disease Modifying Therapies on Neurodegeneration in Multiple Sclerosis

“…Brain atrophy presents in early stages of MS and is associated with physical and cognitive disability [ 8 ]. While in most cases increased BVL or a high rate of BVL can indicate a poor prognosis, it is difficult to generalize all such instances under the same trend [ 9 ].…”