Preventing brain atrophy should be the gold standard of effective therapy in MS (after the first year of treatment): Yes

brain atrophy represents the net effect of the various disease-related processes ongoing in the brain of MS patients. Demyelination, axonal loss, and neurodegeneration are likely contributors to overall tissue loss, as suggested by correlations between lesions and subsequent atrophy. One issue that complicates the use of whole brain atrophy measures in clinical trials is the dynamics of volume change following initiation of anti-inflammatory treatments. Placebocontrolled trials of interferonβ and natalizumab have demonstrated accelerated rates of volume loss in the first year after starting therapy, followed by atrophy deceleration in the second year. 7,8 Increased volume loss in the initial year after antiinflammatory therapy, referred to as ‘pseudoatrophy’, is hypothesized to reflect ongoing tissue loss in addition to a reduction in brain water content related to resolution of inflammation, 9 or perhaps some other type of non-destructive volume loss. Reduced atrophy evident in the second year of anti-inflammatory therapy is thought to reflect ‘secondary neuroprotection’, a beneficial effect related to reduced inflammatory tissue damage. The apparent time lag in treatment effect on atrophy observed in several studies may also be related to the time course of tissue loss following the initial injury that occurs during active inflammation. In the first year of a trial, a portion of the ongoing tissue loss is likely to be due to inflammatory activity that occurred prior to the start of therapy. Therefore, delaying the baseline atrophy scan is recommended in clinical trials. Notably, for many of the approved MS disease-modifying drugs, atrophy reduction relative to placebo in year 2 has clustered in the 40–50% range, suggesting that the rate of tissue loss is reduced but not normalized, and that there may be ongoing neurodegeneration despite effective antiinflammatory therapy. Measurement of white matter lesions alone would not capture these insidious changes. Furthermore, whole brain and gray matter atrophy measures are