Scenario 2: A person with established MS who has been on an injectable 1st-line therapy for several years, with no relapses or focal MRI activity, but has evidence of ongoing brain atrophy above what you would expect for their age, would you change them to a DMT that has been shown to have an effect on brain atrophy?
"What these scenarios are testing is the concept of whether or not we should be incorporating brain atrophy measurements into routine MS clinical practice and whether or we should be incorporating brain atrophy into our definition of NEDA (no-evidence of detectable disease-activity). I suspect this may be premature, but I see no reason why we shouldn't start a debate on the issue."
"What does brain atrophy mean for you as someone with MS? Brain atrophy could mean a lot of things. In general it probably implies ongoing loss of axons and neurones. Brain atrophy cannot be a good thing and there is data that associates it with a poor prognosis."
Fisher E, Lee JC, Nakamura K, Rudick RA. Gray matter atrophy in multiple sclerosis: a longitudinal study. Ann Neurol. 2008 Sep;64(3):255-65. doi: 10.1002/ana.21436.
OBJECTIVE: To determine gray matter (GM) atrophy rates in MSers at all stages of disease, and to identify predictors and clinical correlates of GM atrophy.
METHODS: MSers and healthy control subjects were observed over 4 years with standardized magnetic resonance imaging (MRI) and neurological examinations. Whole-brain, GM, and white matter atrophy rates were calculated. Subjects were categorized by disease status and disability progression to determine the clinical significance of atrophy. MRI predictors of atrophy were determined through multiple regression.
RESULTS: Subjects included 17 healthy control subjects, 7 subjects with clinically isolated syndromes, 36 MSers with relapsing-remitting MS (RRMS), and 27 MSers with secondary progressive MS (SPMS). Expressed as fold increase from control subjects, GM atrophy rate increased with disease stage, from 3.4-fold normal in CISers converting to RRMS to 14-fold normal in SPMS. In contrast, white matter atrophy rates were constant across all MS disease stages at approximately 3-fold normal. GM atrophy correlated with disability. MRI measures of focal and diffuse tissue damage accounted for 62% of the variance in GM atrophy in RRMS, but there were no significant predictors of GM atrophy in SPMS.
INTERPRETATION: Gray matter tissue damage dominates the pathological process as MS progresses, and underlies neurological disabillity. Imaging correlates of gray matter atrophy indicate that mechanisms differ in RRMS and SPMS. These findings demonstrate the clinical relevance of gray matter atrophy in MS, and underscore the need to understand its causes.