Longitudinal multi-modal muscle-based biomarker assessment in motor neuron disease View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-10-17

AUTHORS

Thomas M. Jenkins, James J. P. Alix, Jacob Fingret, Taniya Esmail, Nigel Hoggard, Kathleen Baster, Christopher J. McDermott, Iain D. Wilkinson, Pamela J. Shaw

ABSTRACT

BackgroundClinical 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 methodsA 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.ResultsMND 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.ConclusionMUNIX 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. More... »

PAGES

244-256

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00415-019-09580-x

DOI

http://dx.doi.org/10.1007/s00415-019-09580-x

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1121883784

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/31624953


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