Gray matter atrophy correlates with MS disability progression measured with MSFC but not EDSS
Introduction
Multiple sclerosis has historically been classified as a white matter disease. Conspicuous foci of demyelination are evident post-mortem, and are easily visualized by magnetic resonance imaging (MRI), explaining why MS has long been perceived as a white matter disease. Recently, many studies have demonstrated prominent pathological changes in GM in MS brains as well. These changes include widespread demyelination, activated microglia, apoptotic neurons, and atrophy affecting the cortex, and deep GM structures [1], [2], [3], [4]. Focal GM lesions are not well visualized by conventional MRI scanning, however. Therefore, the time course and relevance of GM pathology has not been fully elucidated.
Magnetic resonance imaging studies have documented that GM volumes are lower in MS patients than in healthy age-matched controls, and some studies have suggested that GM atrophy may begin early in the course of disease [5], [6], [7], [8], [9], [10], [11]. Evolution of GM atrophy over the course of MS, its relationship to disability, and the pathogenesis of GM pathology remain important questions in the MS field. The objective of this study was to determine the clinical relevance of GM atrophy in a spectrum of MS patients, by correlating correlate whole brain, GM, and WM atrophy with sustained disability progression.
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Research subjects
Patients and age- and gender-matched HC subjects were recruited from the Mellen Center. The study was approved by the Cleveland Clinic Institutional Review Board and each subject provided informed consent. Subjects with MS met the International Panel criteria [12] and each had a cranial MRI demonstrating lesions consistent with MS. Patients were classified as RRMS if they had 2 or more relapses with significant neurologic recovery in the prior 3 years, or as SPMS if they reported continued
Results
One hundred six research subjects were enrolled in the original study. Nineteen subjects discontinued the protocol for various reasons; this report provides information on the remaining 87 subjects. These 87 research subjects were observed for a mean of 6.6 years (range: 3.6–7.8 years). Eight of 15 subjects who initially entered with a diagnosis of CIS transitioned to MS during the course of the study; 7 to RRMS, and 1 to SPMS. The remaining 7 CIS patients remained stable and were still
Discussion
Accelerated rates of brain volume loss have been reported in MS patients [16], [17], [18]. Over the years, brain volume declines 5–8 times faster in MS patients than healthy, age-matched controls, leading to the obvious interpretation that loss of brain volume is an end stage consequence of the pathologic processes operating in the disease. However, measures of brain volume are pathologically nonspecific. Fluid shifts may increase or decrease brain volume; gliosis may increased brain volume;
Acknowledgements
This study was supported by the National Institutes of Health NINDS (P01-NS38667) and the National Multiple Sclerosis Society (RG-3099-A). The authors would like to thank Patricia Jagodnik for help with image data management and image analysis, Dee Ivancic, and Claire Hara-Cleaver for assistance with patient visits, Swati Chakraborty, Vicky Konig, and Alan Liu for database development and management, and all the patients and volunteers who kindly agreed to participate in this long-term
References (35)
- et al.
Cortical lesions and brain atrophy in MS
J Neurol Sci
(Jun 15 2005) - et al.
Segmentation of brain magnetic resonance images for measurement of gray matter atrophy in multiple sclerosis patients
NeuroImage
(2009) - et al.
The measurement and clinical relevance of brain atrophy in multiple sclerosis
Lancet Neurol
(Feb 2006) - et al.
Interferon beta-1a for brain tissue loss in patients at presentation with syndromes suggestive of multiple sclerosis: a randomised, double-blind, placebo-controlled trial
Lancet
(Oct 23 2004) - et al.
Grey and white matter atrophy in early clinical stages of primary progressive multiple sclerosis
NeuroImage
(May 2004) - et al.
Gray matter involvement in multiple sclerosis
Neurology
(Feb 27 2007) - et al.
Cortical lesions in multiple sclerosis
Brain
(Jan 1999) - et al.
Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions
Ann Neurol
(Sep 2001) - et al.
Brain atrophy in relapsing–remitting multiple sclerosis: fractional volumetric analysis of gray matter and white matter
Radiology
(Sep 2001) - et al.
Brain atrophy and lesion load in a large population of patients with multiple sclerosis
Neurology
(Jul 26 2005)
Early development of multiple sclerosis is associated with progressive grey matter atrophy in patients presenting with clinically isolated syndromes
Brain
Brain atrophy in clinically early relapsing–remitting multiple sclerosis
Brain
Gray and white matter volume changes in early RRMS: a 2-year longitudinal study
Neurology
Progressive grey matter atrophy in clinically early relapsing–remitting multiple sclerosis
Mult Scler
Gray matter atrophy in multiple sclerosis: a longitudinal study
Ann Neurol
Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”
Ann Neurol
Development of a multiple sclerosis functional composite as a clinical trial outcome measure
Brain
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