Barry Hendin, MD: Multiple sclerosis [MS] is defined as an autoimmune disorder in which the immune system—which should be targeting bacteria, viruses, and pathogens—is instead mis-programmed to attack the myelin of the central nervous system. Unfortunately, the nerve is also an innocent bystander and is injured. In terms of the pathophysiology, think of MS as having 2 components that are operating simultaneously at all times: one is inflammation and the other is degeneration.
Early in MS, the inflammation is the highest. But as we age, the degree of inflammation tends to diminish. Progression is going on at all times and degeneration is going on at all times, but over the course of time it generally increases. So early MS is more inflammatory, less degenerative. Late MS is more degenerative, less inflammatory, but both are simultaneous throughout the course of the disease.
With respect to white matter and gray matter, most of us—certainly most of us in my era—were taught that MS was a white matter disease. We now know that it’s a white matter and gray matter disease. And some of the most important clinical aspects about MS derive from the effect of inflammation and degeneration in the gray matter.
Amit Bar-Or, MD, FRCP, FAAN, FANA: Multiple sclerosis is a very heterogeneous condition that people can experience different forms of, from relapsing-remitting to primary-progressive in onset. And even within those types of MS, the experience can be fairly bland or mild all the through to very aggressive disease, including—at the extreme—MS aggressive enough to decrease life expectancy.
The most aggressive forms of MS may be seen in 1% to 3% of patients, and similarly, MS that had in the past been referred to as benign MS is likely something that is experienced by a very small proportion of patients. It was previously overestimated. But when we start looking at the additional outcome measures beyond just physical disability or the ability to ambulate, we recognize that MS can substantially impact other domains like cognition, upper extremity function, vocation, and socialization. And that these are all important aspects of MS, and its impact that should be considered as part of the appreciation of how aggressive or not the disease is.