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. 2019 Mar 18;9(1):4680.
doi: 10.1038/s41598-019-41240-y.

Muscle contractility in spinobulbar muscular atrophy

Julia R Dahlqvist  1 , Sofie T Oestergaard  2 , Nanna S Poulsen  2 , Kirsten Lykke Knak  2 , Carsten Thomsen  3 , John Vissing  2
Affiliations

Muscle contractility in spinobulbar muscular atrophy

Julia R Dahlqvist et al. Sci Rep. .

Abstract

Spinobulbar muscular atrophy (SBMA) is caused by a trinucleotide repeat expansion in the androgen receptor gene on the X chromosome. There is a toxic effect of the mutant receptor on muscle and neurons resulting in muscle weakness and atrophy. The weakness can be explained by wasting due to loss of muscle cells, but it is unknown whether weakness also relates to poor muscle contractility of the remaining musculature. In this study, we investigated the muscle contractility in SBMA. We used stationary dynamometry and quantitative MRI to assess muscle strength and absolute and fat-free, cross-sectional areas. Specific muscle force (strength per cross-sectional area) and contractility (strength per fat-free cross-sectional area) were compared with healthy controls and their relation to walking distance and disease severity was investigated. Specific force was reduced by 14-49% in SBMA patients compared to healthy controls. Contractility was reduced by 22-39% in elbow flexion, knee extension, ankle dorsi- and plantarflexion in SBMA patients. The contractility decreased with increasing muscle fat content in muscles with affected contractility in SBMA. The decreased muscle contractility in SBMA may relate to motor neuron degeneration and changed fibre type distribution and muscle architecture.

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Conflict of interest statement

J. Vissing has received research and travel support, speaker honoraria from and/or served as consultant on advisory boards for Sanofi/Genzyme, Ultragenyx Pharmaceuticals, and Santhera Pharmaceuticals, Sarepta Therapeutics, Audentes Therapeutics, and Stealth Biotherapeutics. J. Dahlqvist reports no disclosures. S. Oestergaard reports no disclosures. N. Poulsen reports no disclosures. K. Knak reports no disclosures. C. Thomsen reports no disclosures.

Figures

Figure 1
Figure 1
Muscle fat content (a), cross-sectional areas (b), and muscle strength (c) in patients with spinobulbar muscular atrophy and healthy controls. CSA, cross-sectional area; ext., extensors; flex., flexors. Numbers in bars represent the number of participants. Asterisks indicate significant difference.
Figure 2
Figure 2
MR images of upper arm, thigh and calf muscles in one patient with spinobulbar muscular atrophy T1-weighted MR images of the upper arm, thigh and calf in two patients with spinobulbar muscular atrophy.
Figure 3
Figure 3
Contractility in patients with spinobulbar muscular atrophy and controls. CSA, cross-sectional area; CCSA, contractile cross-sectional area; ext., extensors; flex., flexors. Numbers in bars represent the number of participants. Asterisks indicate significant difference.
Figure 4
Figure 4
Correlations between muscle strength and contractile cross-sectional areas in knee extensors (a) and between muscle strength per contractile cross-sectional area and muscle fat content (b) in knee extensors of patients with spinobulbar muscular atrophy and healthy controls. Regression lines indicate significant correlations (dashed line, healthy controls; solid line, patients with SBMA). Significant P- and R-values are specified in the graphs. CCSA, contractile cross-sectional area.
Figure 5
Figure 5
Reduction in strength from first repeat in the intermittent knee extension test in patients with spinobulbar muscular atrophy and healthy controls.
See this image and copyright information in PMC

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