Gray matter fraction (GMF) change is more meaningful than white matter fraction (WMF) as a marker of tissue loss and may be useful to augment whole brain atrophy measurements in MS clinical trials, according to a study of 140 patients with relapsing-remitting MS who were randomized to intramuscular interferon (IFN) beta-1a or placebo. Researchers found:
• Significantly less GM atrophy (during year 2), but not WM atrophy (at any point), was seen with IFN beta-1a compared with placebo.
• Pseudoatrophy effects were more apparent in WM than in GM; in year 1, greater WM volume loss was seen with IFN beta-1a than with placebo, but GM volume loss was similar between groups.
• Risk of sustained disability progression was significantly associated with GM atrophy, but not WM atrophy.
Citation: Fisher E, Nakamura K, Lee JC, You X, Sperling B, Rudick RA. Effect of intramuscular interferon beta-1a on gray matter atrophy in relapsing−remitting multiple sclerosis: a retrospective analysis. [Published online ahead of print August 3, 2015]. Mult Scler. doi: 10.1177/1352458515599072.
Commentary: Understanding a disease requires thorough analysis of its impact. Multiple sclerosis is classically known as a white matter disease. It is also known that MS white matter plaques are in typical subcortical locations. This has been the tenet of MS care and diagnosis by MRI. However, it is also a tenet that MRI changes do not always correlate with clinical exam or disease impact. Many people involved in MS care and research have explored the reason for this discrepancy. This important article is another step along the path of understanding. MS plaques have now been identified within the white matter of the gray matter. This article provides more evidence that the disease impacts gray matter as well as white matter. The atrophy in gray matter correlates more with disease impact and burden than the atrophy in white matter. MS should no longer be considered a disease of white matter or white matter atrophy. Perhaps it’s time to update our diagnostic approach, monitoring of disease impact and progression, and therapeutic intervention efficacy measures as well as the metrics of how we measure disease impact. —Mark Gudesblatt, MD, Medical Director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Islip, NY