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From NMR Research Unit, Departments of Neuroinflammation (Drs. Tiberio, Altmann, Griffin, and Miller, and D.T. Chard, G. Davies, and W. Rashid) and Headache, Brain Injury and Rehabilitation (Drs. Sastre-Garriga and Thompson), Institute of Neurology, and Department of Medical Statistics, School of Hygiene and Tropical Medicine (Dr. Altmann), University College London, UK; and Department of Neurological and Psychiatric Sciences (Dr. Tiberio), University of Padua, Italy.
Address correspondence and reprint requests to Prof. D.H. Miller, NMR Research Group, Institute of Neurology, Queen Square, London WC1N 3BG, UK; e-mail: d.miller{at}ion.ucl.ac.uk
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.
Supported by the MS Society of Great Britain and Northern Ireland (program grant support of the NMR Research Unit). M.T. was supported in part by the Department of Neurologic and Psychiatric Sciences, University of Padua. D.T.C. was supported by a grant from Schering AG, administered by the Institute of Neurology. J.S.-G. was funded through a grant from the Spanish Ministry of Health (BEFI #02/9115).
Received June 9, 2004. Accepted in final form November 29, 2004.
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