Objective To assess clinical, electrophysiological and whole-body muscle MRI measurements of progression in patients with motor neuron disease (MND), as tools for future clinical trials, and to probe pathophysiological mechanisms in vivo.
Methods A prospective, longitudinal, observational, clinicoelectrophysiological and radiological cohort study was performed. Twenty-nine patients with MND and 22 age-matched and gender-matched healthy controls were assessed with clinical measures, electrophysiological motor unit number index (MUNIX) and T2-weighted whole-body muscle MRI, at first clinical presentation and 4 months later. Between-group differences and associations were assessed using age-adjusted and gender-adjusted multivariable regression models. Within-subject longitudinal changes were assessed using paired t-tests. Patterns of disease spread were modelled using mixed-effects multivariable regression, assessing associations between muscle relative T2 signal and anatomical adjacency to site of clinical onset.
Results Patients with MND had 30% higher relative T2 muscle signal than controls at baseline (all regions mean, 95% CI 15% to 45%, p<0.001). Higher T2 signal was associated with greater overall disability (coefficient −0.009, 95% CI −0.017 to –0.001, p=0.023) and with clinical weakness and lower MUNIX in multiple individual muscles. Relative T2 signal in bilateral tibialis anterior increased over 4 months in patients with MND (right: 10.2%, 95% CI 2.0% to 18.4%, p=0.017; left: 14.1%, 95% CI 3.4% to 24.9%, p=0.013). Anatomically, contiguous disease spread on MRI was not apparent in this model.
Conclusions Whole-body muscle MRI offers a new approach to objective assessment of denervation over short timescales in MND and enables investigation of patterns of disease spread in vivo. Muscles inaccessible to conventional clinical and electrophysiological assessment may be investigated using this methodology.
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Contributors TJ, CJM and PJS conceived the idea for the study. TJ drafted the manuscript. All authors revised the manuscript for important intellectual content and gave final approval of the version to be published.
Funding This study was supported by charitable funding with grants from the British Medical Association (Vera Down grant R/140137-11-1) and Ryder Briggs/Neurocare (R/136623-11-1). TJ was supported by a National Institute for Health Research (NIHR) Clinical Lectureship during the conduct of this study. PJS is supported as an NIHR Senior Investigator and by grants from NIHR, the Medical Research Council, the Motor Neurone Disease Association and EU Horizon 2020. This study was supported by the NIHR Sheffield Biomedical Research Centre for Translational Neuroscience.
Disclaimer The funding bodies had no role in the conduct of the study.
Competing interests None declared.
Ethics approval Yorkshire and the Humber Research Ethics Committee (13/YH/0273).
Provenance and peer review Not commissioned; externally peer reviewed.
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