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Magnetization transfer ratio abnormalities reflect clinically relevant grey matter damage in multiple sclerosis

¹ NMR Research Unit, Department of Neuroinflammation, Institute of Neurology, University College London, London, UK
² NMR Research Unit, Department of Neuroinflammation, Institute of Neurology, University College London, London, UK; Medical Statistical Unit, London School of Hygiene and Tropical Medicine, Keppel Street, London, UK
³ Neuroimaging Laboratory, Fondazione Santa Lucia, IRCCS, Rome, Italy
⁴ Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK
⁵ Department of Brain Repair and Rehabilitation, Institute of Neurology, University College London, London, UK

^* To whom correspondence should be addressed.

	Abstract

Background

In multiple sclerosis (MS), grey matter (GM) damage appears more clinically relevant than either white matter (WM) damage or lesion load.

Objective

We investigated if normal-appearing (NA) WM and GM tissue changes assessed by magnetization transfer ratio (MTR) were associated with long-term disability.

Methods

Sixty-nine people were assessed 20 years after presentation with a clinically isolated syndrome (CIS) [28 still CIS, 31 relapsing-remitting MS (RRMS), 10 secondary progressive MS (SPMS)], along with 19 healthy subjects. Mean MTR, peak height (PH) and peak location (PL) of the normalized MTR histograms were determined in NAWM and GM, as well as, WM and GMF fraction (GMF) and T₂-weighted lesion load.

Results

Median expanded disability status scale (EDSS) for MS patients was 2.5 (range 1–8). GM-PH, and less so, NAWM mean and PL, were lower in MS patients (P = 0.009) versus controls, RRMS versus CIS (P = 0.008) and SPMS versus RRMS (P = 0.002). GM-PH (as well as GMF) correlated with EDSS (r_s = -0.49; P = 0.001) and MS functional score (r_s = 0.51; P = 0.001). GM-PH independently predicted disability with similar strength to the associations of GMF with clinical measures.

Conclusion

GM damage was related to long-term disability in an MS cohort with a relatively low median EDSS. Markers of intrinsic GM damage (MTR) and tissue loss offer clinically relevant information in MS.

Key Words: clinically isolated syndromes, grey matter atrophy, lesion load, magnetization transfer ratio, multiple sclerosis, white matter atrophy

First published on May 12, 2009, doi:10.1177/1352458509103715

Multiple Sclerosis 2009;15:668.

A more recent version of this article appeared on June 1, 2009


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