“So as this disease moves along, there’s accelerating gray matter atrophy,” said Dr. Rudick. “And in all stages of MS, gray matter atrophy is at least as significant quantitatively as white matter atrophy.”
Gray matter pathology is also trickier to detect directly and appears to change throughout the course of the disease, according to Dr. Rudick. One study found that disability significantly correlated with gray matter atrophy as early as the clinically isolated syndrome. “Gray matter pathology probably explains disability more than white matter [atrophy],” noted Dr. Rudick. In his four-year study, gray matter atrophy correlated with MR measures in the relapsing-remitting phase but not in the secondary progressive phase.
“Based on atrophy studies, MS is predominantly a gray matter disease,” concluded Dr. Rudick. “It’s not that [MS is] not a white matter disease; there’s a lot going on in the white matter. But gray matter pathology has been relatively unrecognized and seems to be a dominant feature of the disease based on what we’ve seen.”
Dr. Rudick added that as clinical trials for MS therapies continue, ways to measure gray matter atrophy will only become more important. “There’s no real reason to think that a disease-modifying drug with a particular mechanism of action is going to have the same effect in the white matter and the gray matter,” he said. “We’ve been looking at the whole brain, but we really need to start looking at compartments of the brain in terms of effective interventions.… Gray matter atrophy measures should be included in clinical trials if we’re going to be measuring atrophy, so that we can determine the effects of intervention in these different compartments.
—Jessica Dziedzic