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From the Centre for Functional Magnetic Resonance Imaging of the Brain (Drs. Wylezinska, Cifelli, Jezzard, Alecci, and Matthews) and Department of Clinical Neurology (Drs. Cifelli, Palace, and Matthews), University of Oxford, UK.
Address correspondence and reprint requests to Professor P.M. Matthews, Centre for Functional Magnetic Resonance Imaging of the Brain, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, UK; e-mail: paul{at}fmrib.ox.ac.uk
Objective: To define the extent of neuronal injury and loss in thalamic gray matter in patients with relapsing-remitting (RR) MS and to characterize how these neuronal pathologic changes are related to disease duration.
Methods: The authors studied 14 patients with RRMS (Expanded Disability Status Scale score, mean 3.25, range 2.0 to 6.0) and 14 (8 men, 6 women) age-matched healthy controls. Structural MR and MRS studies were performed in a single scanning session using a 3T MR system.
Results: N-acetylaspartate (NAA) concentrations (a measure of the apparent neuronal density) were decreased approximately 11% in the thalami of the patients with RRMS relative to controls (p < 0.05). The patients with RRMS also had an almost 25% lower mean normalized thalamic volume than controls (p < 0.005). Decreases in thalamic NAA concentration correlated strongly with thalamic volume loss for individual patients (r = 0.85, p < 0.01). Both the NAA concentration (r = -0.48, p = 0.044) and normalized thalamic volume (r = -0.60, p = 0.01) were correlated inversely with disease duration. There was a trend for a correlation between the thalamic NAA/creatine (Cr) ratio and the NAA/Cr in the frontal normal-appearing white matter (r = 0.56, p < 0.08).
Conclusions: The reduction of both NAA concentration and thalamic volume suggests that a neurodegenerative component may contribute to the pathology of MS even in the earlier RR stage. The trend toward a relationship between thalamic NAA/Cr and distant normal-appearing white matter changes implies that there may be a common mechanism for the white matter axonal loss and thalamic neuronal injury.
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