Revisiting brain atrophy and its relationship to disability in multiple sclerosis

Abstract

Background: Brain atrophy is a well-accepted imaging biomarker of multiple sclerosis (MS) that partially correlates with both physical disability and cognitive impairment. Methodology/PrincipaI Findings:Based on MRI scans of 60 MS cases and 37 healthy volunteers, we measured the volumes of white matter (WM) lesions, cortical gray matter (GM), cerebral WM, caudate nucleus, putamen, thalamus, ventricles, and brainstem using a validated and completely automated segmentation method. We correlated these volumes with the Expanded Disability Status Scale (EDSS), MS Severity Scale (MSSS), MS Functional Composite (MSFC), and quantitative measures of ankle strength and toe sensation. Normalized volumes of both cortical and subcortical GM structures were abnormally low in the MS group, whereas no abnormality was found in the volume of the cerebral WM. High physical disability was associated with low cerebral WM, thalamus, and brainstem volumes (partial correlation coefficients -0.3-0.4) but not with low cortical GM volume. Thalamus volumes were inversely correlated with lesion load ( r = -0.36, p<0.005). Conclusion: The GM is atrophic in MS. Although lower WM volume is associated with greater disability, as might be expected, WM volume was on average in the normal range. This paradoxical result might be explained by the presence of coexisting pathological processes, such as tissue damage and repair, that cause both atrophy and hypertrophy and that underlie the observed disability. Citation: Shiee N. Bazin P-L, Zackowski KM, Farrell SK, Harrison DM, et al. (201 2) Revisiting Braln Atrophy and Its Relationship to Disability in Multiple Sclerosis. PLoS ONE 76): e37049. doi:10.1371/journal.pone.0037049 Editor: Markus Reindl, lnnsbruck Medical University, Austria Received June 13, 2011; Accepted April 16, 2012; Published May 15. 2012 This IS an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CCO public domain dedication. Funding: This project was partially supported by grants ROlNSOS42SS. ROlNS070906, and K99NS064098 from, and the Intramural Research Program of, the National lnstitute of Neurological Disorders and Stroke; grant K25DA025356 from the Natlonal lnstitute of Drug Abuse; grant SKOlHD049476 from the Eunice Kennedy Shriver National lnstitute for Child Health and Development; grant P41RR015241 from the National Center for Research Resources; grant TR3760A3 from the National Multiple Sclerosis Society; and an unrestricted grant from EMD Serono for MRI data acquisition. The funders had no role In study design, data collection and analysis, decision to publ~sh, or preparatlon of the manuscript. Competing Interests: An unrestricted grant from EMD Serono for MRI data acquisition was received for this study. Daniel 5. Harrlson received fellowship funding from the Partners MS Center o

Key Biomarkers

Symptom Clusters