Gray and white matter volume changes in early RRMS - A 2-year longitudinal study

Background: Brain atrophy, in excess of that seen with normal aging, has been observed early in the clinical course of relapsing-remitting multiple sclerosis ( RRMS). Previous work has suggested that at this stage of the disease, gray matter ( GM) atrophy progresses more rapidly than the white matter ( WM) atrophy. Objectives: To characterize the evolution of GM and WM volumes over 2 years, and their associations with lesion loads in a cohort of patients with clinically early RRMS. Methods: Twenty-one patients with RRMS ( mean age 37.5 years, mean disease duration from symptom onset 2.1 years) and 10 healthy control subjects ( mean age 37.1 years) were studied. Tissue volumes, as fractions of total intracranial volumes, were estimated at baseline and 1- and 2- year follow-up. Brain parenchymal fractions ( BPF), GM fractions ( GMF), and WM fractions ( WMF) were estimated. In subjects with MS, brain lesion loads were determined on conventional T2- weighted along with pre- and post- gadolinium ( Gd) enhanced T1- weighted images at each timepoint. Results: A decrease in GMF was observed in subjects with MS vs normal controls over the 2 years of the study ( mean - 2.1% vs -1.0%, p = 0.044), while no change was seen in WMF over the same period ( mean -0.09% vs + 0.09%, p = 0.812). However, when the MS cohort was divided in half, dependent upon change in Gd-enhancing lesion load over 2 years ( n = 20), a decrease in WMF was seen in the group ( n = 10) with the largest decline in Gd volume, whereas WMF increased in the other half ( n = 10) concurrent with a net increase in volume of Gd-enhancing lesions ( difference between groups: p = 0.034). Conclusions: Increasing gray matter but not white matter ( WM) atrophy was observed early in the clinical course of relapsing- remitting multiple sclerosis. Fluctuations in inflammatory WM lesions appear to be related to volume changes in WM over this time period.