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Magnetization transfer ratio in lesions rather than normal-appearing brain relates to disability in patients with multiple sclerosis

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Abstract

Magnetization transfer ratio (MTR) is a semi-quantitative measure that seems to correlate with the degree of myelin loss and generally tissue destruction in multiple sclerosis (MS). Our objective was to comprehensively assess the MTR of lesions and normal appearing (NA) tissue separately in the white matter (WM), the cortex, the thalamus and the basal ganglia (BG) and determine their relative contribution to disability. In this cross-sectional study 71 patients were included (59 with relapsing–remitting MS, 12 with secondary progressive MS). We used a three-dimensional MTR sequence with high spatial resolution, based on balanced steady-state free precession. Mean MTR was calculated for lesions and NA tissue separately for each tissue type. Lesional MTR was lower than normal-appearing MTR in WM, cortex and thalamus. In the regression analysis, MTR of cortical lesions (β = −0.23, p = 0.05) and MTR of WML (β = −0.21, p = 0.08) were related by trend to the expanded disability status scale. MTR of WML significantly predicted the paced auditory serial-addition test (β = 0.35, p = 0.004). MTR of normal-appearing tissue did not relate to any outcome. Our results suggest that MTR of lesions in the white matter and cortex rather than of normal-appearing tissue relates to disability in patients with MS.

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Abbreviations

bSSFP:

Balanced steady-state free precession

CL:

Cortical lesions

EDSS:

Expanded disability status scale

GM:

Gray matter

MS:

Multiple sclerosis

MTR:

Magnetization transfer ratio

NABG:

Normal-appearing basal ganglia

NACGM:

Normal-appearing cortical gray matter

NAWM:

Normal-appearing white matter

PASAT:

Paced auditory serial-addition task

WM:

White matter

WML:

White matter lesions

9HPT:

9-hole peg test

25 FTW:

25-foot timed walk

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Acknowledgment

Michael Amann received a travel grant from Novartis. Athina Papadopoulou consulted for Teva. She received travel grant from Bayer AG, Teva and UCB-Pharma AG and honoraria from Genzyme and Novartis for lectures, which are exclusively used for research in the University Hospital of Basel. She also received research support from the University of Basel. Michaela Andelova received a travel grant from Novartis. Stefano Magon received a travel grant from Genzyme and Biogen Idec. Nicole Mueller-Lenke consulted for Biogen Idec. Yvonne Naegelin reports no disclosures. The Department of Radiology of University Hospital Basel (coauthors: Christoph Stippich, Michael Amann, Oliver Bieri, Till Sprenger) receives financial support from Bayer Healthcare, Bracco and Guerbet and has a research agreement with SIEMENS Medical Solutions. The submitted work is not related to these agreements. Ernst Wilhelm Radue has received research support (mainly for MS projects) and lecture fees from: Actelion, Basilea, Bayer Schering, Biogen Idec, Merck-Serono and Novartis. Oliver Bieri reports no additional disclosures. Ludwig Kappos participated as principal investigator, member or chair of planning and steering committees or advisory boards in corporate-sponsored clinical trials in multiple sclerosis and other neurological diseases. The sponsoring pharmaceutical companies for these trials include Actelion, Advancell, Allozyne, BaroFold, Bayer Health Care Pharmaceuticals, Bayer Schering Pharma, Bayhill, Biogen Idec, Biotica, CLC Behring, Elan, Genmab, GeNeuro SA, Genmark, GlaxoSmithKline, Genzyme, Johnson & Johnson, Lilly, Merck Serono, Novartis, Novonordisk, Octapharma, Peptimmune, Roche, sanofi-aventis, Santhera, Teva, UCB, Xenoport and Wyeth. The MS Center in Basel has been supported by non-restricted grants from one or more of these companies and by grants from the Swiss MS Society, the Swiss National Research Foundation, the European Union, the Gianni Rubatto, Novartis and Roche Research Foundations. Till Sprenger consulted for ATI, ElectroCore, Genzyme, Novartis, Mitsubishi Pharma, Eli Lilly, Biogen Idec and Allergan. He received travel support from Genzyme, Pfizer, Bayer Schering, Eli Lilly and Allergan. He received research support from and the Swiss MS Society, the Swiss National Science Foundation, Novartis Pharmaceuticals Switzerland and the EFIC-Grünenthal grant.

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Correspondence to Till Sprenger.

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M. Amann and A. Papadopoulou contributed equally to the manuscript.

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Amann, M., Papadopoulou, A., Andelova, M. et al. Magnetization transfer ratio in lesions rather than normal-appearing brain relates to disability in patients with multiple sclerosis. J Neurol 262, 1909–1917 (2015). https://doi.org/10.1007/s00415-015-7793-5

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