Gray matter atrophy is related to long-term disability in multiple sclerosis
Corresponding Author
Leonora K. Fisniku MRCP
Nuclear Magnetic Resonance Research Unit, Institute of Neurology, University College London, United Kingdom
Department of Neuroinflammation, Institute of Neurology, University College London, United Kingdom
NMR Research Unit, Institute of Neurology, Queen Square, London WC1N 3BG, United KingdomSearch for more papers by this authorDeclan T. Chard PhD
Nuclear Magnetic Resonance Research Unit, Institute of Neurology, University College London, United Kingdom
Department of Neuroinflammation, Institute of Neurology, University College London, United Kingdom
Search for more papers by this authorJonathan S. Jackson MSci
Nuclear Magnetic Resonance Research Unit, Institute of Neurology, University College London, United Kingdom
Department of Neuroinflammation, Institute of Neurology, University College London, United Kingdom
Search for more papers by this authorValerie M. Anderson BSci
Nuclear Magnetic Resonance Research Unit, Institute of Neurology, University College London, United Kingdom
Department of Neuroinflammation, Institute of Neurology, University College London, United Kingdom
Search for more papers by this authorDaniel R. Altmann PhD
Nuclear Magnetic Resonance Research Unit, Institute of Neurology, University College London, United Kingdom
Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, University College London, United Kingdom
Search for more papers by this authorKatherine A. Miszkiel MRCP
Department of Brain Repair and Rehabilitation, Institute of Neurology, University College London, United Kingdom
Search for more papers by this authorAlan J. Thompson PhD
Nuclear Magnetic Resonance Research Unit, Institute of Neurology, University College London, United Kingdom
Medical Statistical Unit, London School of Hygiene and Tropical Medicine, London, United Kingdom
Search for more papers by this authorDavid H. Miller MD
Nuclear Magnetic Resonance Research Unit, Institute of Neurology, University College London, United Kingdom
Department of Neuroinflammation, Institute of Neurology, University College London, United Kingdom
Search for more papers by this authorCorresponding Author
Leonora K. Fisniku MRCP
Nuclear Magnetic Resonance Research Unit, Institute of Neurology, University College London, United Kingdom
Department of Neuroinflammation, Institute of Neurology, University College London, United Kingdom
NMR Research Unit, Institute of Neurology, Queen Square, London WC1N 3BG, United KingdomSearch for more papers by this authorDeclan T. Chard PhD
Nuclear Magnetic Resonance Research Unit, Institute of Neurology, University College London, United Kingdom
Department of Neuroinflammation, Institute of Neurology, University College London, United Kingdom
Search for more papers by this authorJonathan S. Jackson MSci
Nuclear Magnetic Resonance Research Unit, Institute of Neurology, University College London, United Kingdom
Department of Neuroinflammation, Institute of Neurology, University College London, United Kingdom
Search for more papers by this authorValerie M. Anderson BSci
Nuclear Magnetic Resonance Research Unit, Institute of Neurology, University College London, United Kingdom
Department of Neuroinflammation, Institute of Neurology, University College London, United Kingdom
Search for more papers by this authorDaniel R. Altmann PhD
Nuclear Magnetic Resonance Research Unit, Institute of Neurology, University College London, United Kingdom
Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, University College London, United Kingdom
Search for more papers by this authorKatherine A. Miszkiel MRCP
Department of Brain Repair and Rehabilitation, Institute of Neurology, University College London, United Kingdom
Search for more papers by this authorAlan J. Thompson PhD
Nuclear Magnetic Resonance Research Unit, Institute of Neurology, University College London, United Kingdom
Medical Statistical Unit, London School of Hygiene and Tropical Medicine, London, United Kingdom
Search for more papers by this authorDavid H. Miller MD
Nuclear Magnetic Resonance Research Unit, Institute of Neurology, University College London, United Kingdom
Department of Neuroinflammation, Institute of Neurology, University College London, United Kingdom
Search for more papers by this authorAbstract
Objective
To determine the relation of gray matter (GM) and white matter (WM) brain volumes, and WM lesion load, with clinical outcomes 20 years after first presentation with clinically isolated syndrome suggestive of multiple sclerosis (MS).
Methods
Seventy-three patients were studied a mean of 20 years from first presentation with a clinically isolated syndrome (33 of whom developed relapsing-remitting MS and 11 secondary-progressive MS, with the rest experiencing no further definite neurological events), together with 25 healthy control subjects. GM and WM volumetric measures were obtained from three-dimensional T1-weighted brain magnetic resonance images using Statistical Parametric Mapping 2.
Results
Significant GM (p < 0.001) and WM atrophy (p = 0.001) was seen in MS patients compared with control subjects. There was significantly more GM, but not WM atrophy, in secondary-progressive MS versus relapsing-remitting MS (p = 0.003), and relapsing-remitting MS versus clinically isolated syndrome (p < 0.001). GM, but not WM, fraction correlated with expanded disability status scale (rs = −0.48; p < 0.001) and MS Functional Composite scores (rs = 0.59; p < 0.001). WM lesion load correlated with GM (rs = −0.63; p < 0.001), but not with WM fraction. Regression modeling indicated that the GM fraction explained more of the variability in clinical measures than did WM lesion load.
Interpretation
In MS patients with a relatively long and homogeneous disease duration, GM atrophy is more marked than WM atrophy, and reflects disease subtype and disability to a greater extent than WM atrophy or lesions. Ann Neurol 2008
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