Jenkins, T.M., Alix, J.J.P. orcid.org/0000-0001-8391-9749, Fingret, J. et al. (6 more authors) (2020) Longitudinal multi-modal muscle-based biomarker assessment in motor neuron disease. Journal of Neurology, 267 (1). pp. 244-256. ISSN 0340-5354
Abstract
Background
Clinical phenotypic heterogeneity represents a major barrier to trials in motor neuron disease (MND) and objective surrogate outcome measures are required, especially for slowly progressive patients. We assessed responsiveness of clinical, electrophysiological and radiological muscle-based assessments to detect MND-related progression.
Materials and methods
A prospective, longitudinal cohort study of 29 MND patients and 22 healthy controls was performed. Clinical measures, electrophysiological motor unit number index/size (MUNIX/MUSIX) and relative T2- and diffusion-weighted whole-body muscle magnetic resonance (MR) were assessed three times over 12 months. Multi-variable regression models assessed between-group differences, clinico-electrophysiological associations, and longitudinal changes. Standardized response means (SRMs) assessed sensitivity to change over 12 months.
Results
MND patients exhibited 18% higher whole-body mean muscle relative T2-signal than controls (95% CI 7–29%, p < 0.01), maximal in leg muscles (left tibialis anterior 71% (95% CI 33–122%, p < 0.01). Clinical and electrophysiological associations were evident. By 12 months, 16 patients had died or could not continue. In the remainder, relative T2-signal increased over 12 months by 14–29% in right tibialis anterior, right quadriceps, bilateral hamstrings and gastrocnemius/soleus (p < 0.01), independent of onset-site, and paralleled progressive weakness and electrophysiological loss of motor units. Highest clinical, electrophysiological and radiological SRMs were found for revised ALS-functional rating scale scores (1.22), tibialis anterior MUNIX (1.59), and relative T2-weighted leg muscle MR (right hamstrings: 0.98), respectively. Diffusion MR detected minimal changes.
Conclusion
MUNIX and relative T2-weighted MR represent objective surrogate markers of progressive denervation in MND. Radiological changes were maximal in leg muscles, irrespective of clinical onset-site.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019 The Authors. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
Keywords: | Muscle; MRI; Motor neuron disease; Amyotrophic lateral sclerosis; MUNIX |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 11 Nov 2019 12:48 |
Last Modified: | 16 Dec 2021 16:58 |
Status: | Published |
Publisher: | Springer Science and Business Media LLC |
Refereed: | Yes |
Identification Number: | 10.1007/s00415-019-09580-x |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:153309 |
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Filename: Jenkins2019_Article_LongitudinalMulti-modalMuscle-.pdf
Licence: CC-BY 4.0