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Regional Gray Matter Atrophy in Early Primary Progressive Multiple Sclerosis
A Voxel-Based Morphometry Study
Jorge Sepulcre, MD;
Jaume Sastre-Garriga, MD;
Mara Cercignani, PhD;
Gordon T. Ingle, MRCP;
David H. Miller, FRCP;
Alan J. Thompson, FRCP
Arch Neurol. 2006;63:1175-1180.
Background Gray matter (GM) atrophy has been reported in multiple sclerosis (MS). However, little is known about its regional distribution.
Objective To investigate the regional distribution of GM atrophy in clinically early primary progressive MS (PPMS).
Design and Patients Thirty-one patients with PPMS within 5 years of symptom onset (mean age, 43.2 years; median Expanded Disability Status Scale score, 4.5) and 15 healthy control subjects (mean age, 43.7 years) were studied. All subjects underwent a 3-dimensional inversion-recovery fast spoiled gradient-recalled echo sequence that was repeated after 1 year in patients only. Magnetic resonance images underwent an optimized voxel-based morphometric analysis that segments magnetic resonance data volumes in a normalized space and quantifies tissue atrophy on a voxel-by-voxel basis. A lesion mask was created for each patient and used in normalization and segmentation steps to minimize bias from lesions. A multisubject design was used in the cross-sectional study to compare patients with PPMS and controls. A 1-way analysis of variance (within-subjects) design was used in the longitudinal study.
Results At baseline, patients with PPMS displayed bilateral thalamic atrophy compared with controls. In addition, a significant association between lesion load and decreased GM volume was found for the thalami. Loss of GM in the putamen, caudate, thalami, and cortical and infratentorial areas was observed in patients after 1 year of follow-up.
Conclusions Atrophy is most obvious in deep GM in clinically early PPMS. This may reflect increased sensitivity of these regions to neurodegeneration. Cortical and infratentorial atrophy developed as the disease evolved.
Author Affiliations: Institute of Neurology, University College of London, London, England.
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