Predicting clinical progression in patients with relapsing remitting multiple sclerosis retrospectively using a myelin content proxy

Background : Progression independent of relapse- and magnetic resonance imaging (MRI)-activity (PIRMA) in relapsing-remitting multiple sclerosis (RRMS) may result from subtle myelin pathology in normal-appearing white matter (NAWM) and perilesions. Objective : To evaluate short-term myelin changes, estimated with the MRI-based T1w/FLAIR ratio, associations with long-term clinical progression in patients with RRMS receiving natalizumab. Methods : For 29 patients with RRMS, short-term, six-month myelin changes were calculated for three areas, i.e. white matter hyperintensities (WMH), a perilesional area of 2 mm, and NAWM. Expanded disability status scale (EDSS) scores at baseline and after at least three years were used to define long-term clinical progression. Results : Logistic regression models demonstrated significant associations between long-term progression using short-term changes in myelin proxy in NAWM ( β = -77.962; p = .039), but not in perilesional tissue ( β = -3.999; p = .717) and WMH ( β = -4.324; p = .752). ROC-curve of the logistic regression model of NAWM showed a good discriminative value (area under the curve (AUC) = .892, 95% CI [.755-1.000]) for clinical progression. Conclusion : By assessing short-term myelin changes outside lesions, using readily available clinical MRI scans, long-term clinical progression in patients with RRMS may be predicted.