Lower extremity muscle pathology in myotonic dystrophy type 1 assessed by quantitative MRI

Heskamp, L., van Nimwegen, M., Ploegmakers, M. J., Bassez, G., Deux, J.-F., Cumming, S. A., Monckton, D. G. , van Engelen, B. G.M. and Heerschap, A. (2019) Lower extremity muscle pathology in myotonic dystrophy type 1 assessed by quantitative MRI. Neurology, 92(24), e2803-e2814. (doi: 10.1212/WNL.0000000000007648) (PMID:31118244) (PMCID:PMC6598795)

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Abstract

Objective: To determine the value of quantitative MRI in providing imaging biomarkers for disease in 20 different upper and lower leg muscles of patients with myotonic dystrophy type 1 (DM1). Methods: We acquired images covering these muscles in 33 genetically and clinically well-characterized patients with DM1 and 10 unaffected controls. MRIs were recorded with a Dixon method to determine muscle fat fraction, muscle volume, and contractile muscle volume, and a multi-echo spin-echo sequence was used to determine T2 water relaxation time (T2water), reflecting putative edema. Results: Muscles in patients with DM1 had higher fat fractions than muscles of controls (15.6 ± 11.1% vs 3.7 ± 1.5%). In addition, patients had smaller muscle volumes (902 ± 232 vs 1,097 ± 251 cm3), smaller contractile muscle volumes (779 ± 247 vs 1,054 ± 246 cm3), and increased T2water (33.4 ± 1.0 vs 31.9 ± 0.6 milliseconds), indicating atrophy and edema, respectively. Lower leg muscles were affected most frequently, especially the gastrocnemius medialis and soleus. Distribution of fat content per muscle indicated gradual fat infiltration in DM1. Between-patient variation in fat fraction was explained by age (≈45%), and another ≈14% was explained by estimated progenitor CTG repeat length (r2 = 0.485) and somatic instability (r2 = 0.590). Fat fraction correlated with the 6-minute walk test (r = −0.553) and muscular impairment rating scale (r = 0.537) and revealed subclinical muscle involvement. Conclusion: This cross-sectional quantitative MRI study of 20 different lower extremity muscles in patients with DM1 revealed abnormal values for muscle fat fraction, volume, and T2water, which therefore may serve as objective biomarkers to assess disease state of skeletal muscles in these patients.

Item Type:Articles
Additional Information:Funding provided by the European Union's Seventh Framework Programme for research, technological development and demonstration (grant agreement 305697).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Monckton, Professor Darren and Cumming, Dr Sarah
Authors: Heskamp, L., van Nimwegen, M., Ploegmakers, M. J., Bassez, G., Deux, J.-F., Cumming, S. A., Monckton, D. G., van Engelen, B. G.M., and Heerschap, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Neurology
Publisher:American Academy of Neurology
ISSN:1526-632X
ISSN (Online):1526-632X
Published Online:22 May 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Neurology 92(24):e2803-e2814
Publisher Policy:Reproduced under a Creative Commons License

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