TY - JOUR
T1 - Revisiting brain atrophy and its relationship to disability in multiple sclerosis
AU - Shiee, Navid
AU - Bazin, Pierre Louis
AU - Zackowski, Kathleen M.
AU - Farrell, Sheena K.
AU - Harrison, Daniel M.
AU - Newsome, Scott D.
AU - Ratchford, John N.
AU - Caffo, Brian S.
AU - Calabresi, Peter A.
AU - Pham, Dzung L.
AU - Reich, Daniel S.
N1 - Funding Information:
This project was partially supported by grants R01NS054255, R01NS070906, and K99NS064098 from, and the Intramural Research Program of, the National Institute of Neurological Disorders and Stroke; grant K25DA025356 from the National Institute of Drug Abuse; grant 5K01HD049476 from the Eunice Kennedy Shriver National Institute 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 publish, or preparation of the manuscript.
Funding Information:
Funding: This project was partially supported by grants R01NS054255, R01NS070906, and K99NS064098 from, and the Intramural Research Program of, the National Institute of Neurological Disorders and Stroke; grant K25DA025356 from the National Institute of Drug Abuse; grant 5K01HD049476 from the Eunice Kennedy Shriver National Institute 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 publish, or preparation of the manuscript.
Funding Information:
Competing Interests: An unrestricted grant from EMD Serono for MRI data acquisition was received for this study. Daniel S. Harrison received fellowship funding from the Partners MS Center of Brigham and Women’s Hospital, Boston, MA and research funding from Bayer Schering Pharma. Scott D. Newsome received fellowship funding from the National MS Society (Sylvia Lawry Physician Fellowship) and has received consultant fees from Biogen-IDEC. John N. Ratchford received research support from the Nancy Davis Foundation for MS and support for clinical trials from Novartis, Biogen-Idec, and the University of California-Los Angeles. Brian S. Caffo received funding from Merck Pharmacueticals and Pfizer Pharmaceuticals. Peter A. Calabresi received grants from Biogen-IDEC, Teva, Vertex, Bayer, Genentech, Abbott Labs, and EMD Serono. He received consulting fees from Novartis, Biogen-IDEC, and Teva. There are no patents, products in development, or marketed products to declare. This does not alter the authors’ adherence to all the PLoS ONE policies on sharing data and materials.
Publisher Copyright:
© 2012 Public Library of Science. All Rights Reserved.
PY - 2012/5
Y1 - 2012/5
N2 - Background: Brain atrophy is a well-accepted imaging biomarker of multiple sclerosis (MS) that partially correlates with both physical disability and cognitive impairment. Methodology/Principal 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 = 20.36, 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.
AB - Background: Brain atrophy is a well-accepted imaging biomarker of multiple sclerosis (MS) that partially correlates with both physical disability and cognitive impairment. Methodology/Principal 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 = 20.36, 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.
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U2 - 10.1371/journal.pone.0037049
DO - 10.1371/journal.pone.0037049
M3 - Article
C2 - 22615886
AN - SCOPUS:84871604801
VL - 7
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 5
M1 - e37049
ER -