Abstract
The purpose of this study was to provide imaging evidence of increased glycosaminoglycan (GAG) content in patients with post-stroke muscle stiffness; and to determine the effect of hyaluronidase treatment on intramuscular GAG content. In this prospective study, we used 3D-T1ρ (T1rho) magnetic resonance (MR) mapping of the upper arm muscles to quantify GAG content in patients with post-stroke muscle stiffness before and after hyaluronidase injection treatment. For this study, healthy controls (n = 5), and patients with post-stroke muscle stiffness (n = 5) were recruited (March 2017–April 2018). T1ρ MR imaging and Dixon water-fat MR imaging of the affected upper arms were performed before and after off-label treatment with hyaluronidase injections. T1ρ mapping was done using a three-parameter non-linear mono-exponential fit. Wilcoxon Mann-Whitney test was used to compare patients’ vs controls and pre- vs post-treatment conditions. The T1ρ values in the biceps were significantly higher in patients before treatment (34.04 ± 4.39 ms) compared with controls (26.70 ± 0.54 ms; P = 0.006). Significant improvement was seen in the biceps of patients before (35.48 ± 3.38 ms) and after treatment (29.45 ± 1.23 ms; P = 0.077). Dixon water-fat distribution was not significantly different in the patients compared to the controls (biceps P = 0.063; triceps P = 0.190). These results suggest that T1ρ mapping can be used to quantify GAG content in the muscles of patients with post-stroke muscle stiffness, and that muscle hyaluronan content is increased in stiff muscles compared with controls, providing imaging corroboration for the hyaluronan hypothesis of muscle stiffness.
Highlights
Stroke is a leading cause of disability in adults, with a total direct and indirect economic cost of over $40 billion in the US in 2013–20141
The hyaluronan hypothesis proposes that the accumulation of the hyaluronan, within the extra-cellular matrix (ECM) of muscles contributes to the development of muscle stiffness[16]
We demonstrate that T1ρ magnetic resonance (MR) imaging can be employed to assess the GAG content in muscles post stroke in comparison to control subjects
Summary
Stroke is a leading cause of disability in adults, with a total direct and indirect economic cost of over $40 billion in the US in 2013–20141. While hyperreflexia develops relatively early after neurologic injury, muscle stiffness develops over the ensuing weeks and months[13] This increases the resistance to movement making it more challenging to move and participate in therapy. Non-neural mechanisms have been proposed to explain the increased resistance to movement which may result from secondary changes in the structure or function of skeletal muscles secondary to the neural injury[14]. A recent case series showed that off-label, intramuscular injections of the enzyme hyaluronidase which hydrolyzes hyaluronan, resulted in reduced muscle stiffness and increased the range of passive and active motion in the post-stroke arm with beneficial effects lasting over three months[16,20]. The purpose of this study was to i) provide imaging evidence of increased GAG content in patients with post-stroke muscle stiffness; and ii) to determine the effect of hyaluronidase treatment on intramuscular GAG content
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