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

NMR Research Unit, Department of Neuroinflammation, Institute of Neurology, University College London, London, UKl.fisniku{at}ion.ucl.ac.uk

DR Altmann

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

M Cercignani

Neuroimaging Laboratory, Fondazione Santa Lucia, IRCCS, Rome, Italy

DJ Tozer

NMR Research Unit, Department of Neuroinflammation, Institute of Neurology, University College London, London, UK

DT Chard

NMR Research Unit, Department of Neuroinflammation, Institute of Neurology, University College London, London, UK

JS Jackson

NMR Research Unit, Department of Neuroinflammation, Institute of Neurology, University College London, London, UK

KA Miszkiel

Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK

K Schmierer

NMR Research Unit, Department of Neuroinflammation, Institute of Neurology, University College London, London, UK

AJ Thompson

Department of Brain Repair and Rehabilitation, Institute of Neurology, University College London, London, UK

DH Miller

NMR Research Unit, Department of Neuroinflammation, Institute of Neurology, University College London, London, UK

Background

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

Objective

We investigated if normal-appearing white matter (NAWM) and grey matter tissue changes assessed by magnetization transfer ratio 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 multiple sclerosis, 10 secondary progressive multiple sclerosis], along with 19 healthy subjects. Mean magnetization transfer ratio, peak height (PH) and peak location of the normalized magnetization transfer ratio histograms were determined in NAWM and grey matter, as well as, white matter and GM Fraction (GMF) and T₂-weighted lesion load.

Results

Median expanded disability status scale for multiple sclerosis patients was 2.5 (range 1–8). GM-PH, and less so, NAWM mean and peak location, were lower in multiple sclerosis patients (P = 0.009) versus controls, relapsing-remitting multiple sclerosis versus CIS (P = 0.008) and secondary progressive multiple sclerosis versus relapsing-remitting multiple sclerosis (P = 0.002). GM-PH (as well as GMF) correlated with expanded disability status scale (r_s = –0.49; P = 0.001) and multiple sclerosis 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

Grey matter damage was related to long-term disability in multiple sclerosis cohort with a relatively low median expanded disability status scale. Markers of intrinsic grey matter damage (magnetization transfer ratio) and tissue loss offer clinically relevant information in multiple sclerosis.

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

This version was published on June 1, 2009

Multiple Sclerosis, Vol. 15, No. 6, 668-677 (2009)
DOI: 10.1177/1352458509103715


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