Effects of Duchenne muscular dystrophy on muscle stiffness and response to electrically-induced muscle contraction: A 12-month follow-up

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Highlights

  • DMD patients exhibit a progressive impairment of muscle force transmission.

  • Electromechanical delay is sensitive to quantify degenerative effects of DMD.

  • Increase in muscle stiffness indicates tissue changes over 12 months in DMD.

  • Electromechanical delay and elastography may help detect muscle impairments for research purposes.

Abstract

The present study aimed to assess the ability of muscle stiffness (shear modulus) and response to electrically-induced muscle contraction to detect changes in muscle properties over a 12-month period in children with Duchenne muscular dystrophy (DMD). Ten children with DMD and nine age-matched healthy male controls participated in two experimental sessions (T0 and T+12months) separated by 12.4 ± 0.9 months. Two contractions of the biceps brachii were electrically-induced during which an ultrasound probe was placed over the muscle. The resting shear modulus was measured using elastography from six muscles. Evoked maximal torque was increased at T+12months in controls (+11.2 ± 7.6%, P <0.001) but was not modified in children with DMD (P = 0.222). Electromechanical delay (+12.9 ± 11.3%, P <0.001) and its force transmission component (+10.1 ± 21.6%, P = 0.003) were significantly longer at T+12months than T0 for children with DMD. The results revealed an increase in muscle stiffness at T+12months in children with DMD for tibialis anterior (+75.1 ± 93.5%, P= 0.043), gastrocnemius medialis (+144.8 ± 180.6%, P= 0.050) and triceps brachii (+35.5 ± 32.2%, P= 0.005). This 12-month follow-up study demonstrates that electromechanical delay and elastography may help detect subtle muscle impairments in patients with DMD. These sensitive outcomes may improve the follow-up of innovative therapeutic interventions within the field of DMD.

Introduction

Promising therapeutic options are being developed for children with Duchenne muscular dystrophy (DMD) [1], [2]. Because some therapies aim to target a specific muscle or limb region [3], [4], the development of non-invasive and sensitive methods to locally assess both muscle function and muscle biomechanics is needed. Recent studies have revealed the potential of two approaches that have the advantage of obviating voluntary and maximal contraction by the patients [5], [6].

The first approach is the electromechanical delay (EMD), defined as the time lag between the onset of muscle activation and onset of force production [7]. EMD can be assessed during electrically-induced contractions using very high frame rate ultrasound (up to 5 kHz) [8], [9], [10]. The first part of the EMD is the delay between muscle electrical stimulation and the onset of muscle fascicle motion, which is mainly attributed to electrochemical processes such as the excitation–contraction coupling. Its second part is the delay between the onset of fascicle motion and the onset of force production, which is attributed to the force transmission processes. By determining the time required for the electrochemical and mechanical processes this technique provides information on both the function and the biomechanics of a targeted muscle. Applying this method to children with DMD, Lacourpaille et al. [5] reported a longer EMD in patients with DMD compared to healthy age-matched participants. This was mainly explained by an increased time required for the force to be transmitted to the skeleton (+75%). In addition, the electrically-evoked torque was lower in children with DMD.

Second, resting muscle stiffness can be reliably estimated in DMD using ultrasound shear wave elastography [6], [11]. Although an increased stiffness was found in these patients for five muscles (tibialis anterior, gastrocnemius medialis, vastus lateralis, biceps brachii and triceps brachii), there was no change for the distal abductor digiti minimi muscle (hand muscle) [6]. This latter result is in line with previous works showing that DMD progresses according to a proximal-distal pattern [12].

The assessment of both muscle stiffness and responses to electrically-induced contractions (EMD and torque amplitude) can provide important information related to muscle function and structure with potential relevance to clinical and therapeutic assessments. In order to bring new arguments for the use of these innovative biomechanical approaches, the present study aimed to assess their ability to detect changes in muscle properties over a 12-month period in children with DMD. We hypothesized that both muscle stiffness and the electromechanical delay would be increased after a 12-month period in patients with DMD.

Section snippets

Participants

Ten DMD patients (genetically confirmed) and nine age-matched healthy controls volunteered to participate (Table 1). The experimental procedures were approved by the local ethics committee (Nantes Ouest IV – CPP-MIP-004) and all of the procedures conformed to the declaration of Helsinki. All the control subjects and patients with DMD have been previously reported elsewhere [5], [6]. These prior articles dealt with the effects of DMD on muscle stiffness and response to electrically-induced

Results

No significant time × group interaction was found for Imax (P = 0.163). The mean Imax was 83.4 ± 20.5 mA. When considering the electrically-induced contractions, no significant time × group interaction was observed for Dm (P = 0.455) but a significant time × group interaction was found for EMD (P = 0.008), Tm (P = 0.039) and evoked maximal torque (P <0.001). Post hoc analyses revealed that the evoked maximal torque increased at T+12months in controls (+11.2 ± 7.6%, d= 2.1, P <0.001) but Tm (P

Discussion

This 12 month follow-up study demonstrated the ability of two non-invasive approaches to detect changes in both muscle function and muscle biomechanics in children with DMD. Interestingly, the present data showed a progressive lengthening of the time required for the muscle force to be transmitted to the skeleton in patients with DMD while maximally evoked torque was unchanged. It therefore suggests that, during childhood, growth and maturation may partly compensate for strength decrease but

Conclusions

Overall, the non-invasive and localized evaluation methods used in this study offer a unique opportunity to non-invasively assess muscle stiffness, force transmission and force production in patients with DMD. The development of such assessments could contribute to a better understanding of the origin of progressive impairments in two key-domains: muscle contracture and muscle weakness. The results suggest that, during childhood, growth and maturation may partly compensate for strength decrease

Funding

This study was supported by grants from the French Muscular Dystrophy Association (AFM, contract no. 18846) and the Région Pays de la Loire (QUETE project, no. 2015-09035).

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    These authors contributed equally to this work.

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