Brain atrophy in multiple sclerosis: what we know and would like to know.

Brain and spinal cord atrophy measures are becoming standard in multiple sclerosis (MS) clinical trials, yet we know little about the underlying mechanisms resulting in atrophy, or the factors accounting for variable rates of atrophy in individuals and across the MS phenotype. We do not understand, as yet, why apparently effective treatment does or does not affect atrophy. Some limitations of this measure may be accounted for by complex structural and temporal factors that become active at the initiation of injury, but are not immediately expressed. Additional limitations include differential effects related to the focal versus diffuse pathology in MS, and variable expression of the pathology underlying atrophy, depending on location in central nervous system (CNS) tissue.