Muscle shear modulus measured with ultrasound shear‐wave elastography across a wide range of contraction intensity

Introduction: In this study we examine the repeatability of measuring muscle shear modulus using ultrasound shear‐wave elastography between trials and between days, and the association between shear modulus and contraction intensity over a wide range of intensities. Methods: Shear modulus of the biceps brachii was determined using ultrasound shear‐wave elastography during static elbow flexion (up to 60% of maximal contraction) in healthy young adults. Results: The correspondence of shear modulus was confirmed in phantoms between the manufacturer‐calibrated values and the shear‐wave elastography values. The intraclass correlation coefficient of muscle shear modulus was high: 0.978 between trials and 0.948 between days. Shear modulus increased linearly with elbow flexion torque across contraction intensity, and its slope was associated negatively with muscle strength. Conclusions: Muscle shear modulus measured with ultrasound shear‐wave elastography may be useful for inferring muscle stiffness across a wide range of contraction intensity. In addition, it has high repeatability between trials and between days. Muscle Nerve 50 : 103–113, 2014     

Posture‐induced changes in peripheral nerve stiffness measured by ultrasound shear‐wave elastography

Introduction: Peripheral nerves slide and stretch during limb movements. Changes in nerve stiffness associated with such movements have not been examined in detail but may be important in understanding movement‐evoked pain in patients with a variety of different musculoskeletal conditions. Methods: Shear‐wave elastography was used to examine stiffness in the median and tibial nerves of healthy individuals during postures used clinically to stretch these nerves. Results: Shear‐wave velocity increased when limbs were moved into postures that are thought to increase nerve stiffness (mean increase: median nerve = 208% in arm, 236% in forearm; tibial nerve = 136%). There was a trend toward a negative correlation between age and shear‐wave velocity (r = 0.58 for tibial nerve). Conclusions: Shear‐wave elastography provides a tool for examining nerve biomechanics in healthy individuals and patients. However, limb position, age, and effects of nerve tension on neural architecture should be taken into consideration. Muscle Nerve 55 : 213–222, 2017     

Non‐invasive assessment of muscle stiffness in patients with duchenne muscular dystrophy

ABSTRACT: Introduction: Assessment of muscle mechanical properties may provide clinically valuable information for follow‐up of patients with Duchenne muscular dystrophy (DMD) through the course of their disease. In this study we aimed to assess the effect of DMD on stiffness of relaxed muscles using elastography (supersonic shear imaging). Methods: Fourteen DMD patients and 13 control subjects were studied. Six muscles were measured at 2 muscle lengths (shortened and stretched): gastrocnemius medialis (GM); tibialis anterior (TA); vastus lateralis (VL); biceps brachii (BB); triceps brachii (TB); and abductor digiti minimi (ADM). Results: Stiffness was significantly higher in DMD patients compared with controls for all the muscles (main effect for population, P < 0.033 in all cases), except for ADM. The effect size was small (d = 0.33 for ADM at both muscle lengths) to large (d = 0.86 for BB/stretched). Conclusions: Supersonic shear imaging is a sensitive non‐invasive technique to assess the increase in muscle stiffness associated with DMD. Muscle Nerve 51 : 284–286, 2015     

Skeletal muscle stiffness as measured by magnetic resonance elastography after chronic spinal cord injury: a cross-sectional pilot study

Skeletal muscle stiffness is altered after spinal cord injury(SCI). Assessing muscle stiffness is essential for rehabilitation and pharmaceutical interventions design after SCI. The study used magnetic resonance elastography to assess the changes in stiffness after chronic SCI compared to matched able-bodied controls and determine its association with muscle size, spasticity, and peak torque in persons with SCI. Previous studies examined the association between muscle stiffness and spasticity, however, we are unaware of other studies that examined the effects of muscle composition on stiffness after SCI. Ten participants(one female) with chronic SCI and eight(one female) matched able-bodied controls participated in this cross-sectional study. Magnetic resonance elastography was utilized to monitor stiffness derived from shear waves propagation. Modified Ashworth scale was used to evaluate spasticity scores in a blinded fashion. Peak isometric and isokinetic torques were measured using a biodex dynamometer. Stiffness values were non-significantly lower(12.5%; P = 0.3) in the SCI group compared to able-bodied controls. Moreover, stiffness was positively related to vastus lateralis whole muscle cross-sectional area(CSA)(r~2 = 0.64, P 0.005) and vastus lateralis absolute muscle CSA after accounting for intramuscular fat(r~2 = 0.78, P 0.0007). Stiffness was also positively correlated to both isometric(r~2= 0.55–0.57, P 0.05) and isokinetic peak(r~2= 0.46–0.48, P 0.05) torques. Our results suggest that larger clinical trial is warranted to confirm the preliminary findings that muscle stiffness is altered after SCI compared to healthy controls. Stiffness appeared to be influenced by infiltration of intramuscular fat and modestly by the spasticity of the paralyzed muscles. The preliminary data indicated that the relationship between muscle stiffness and peak torque is not altered with changing the frequency of pulses or angular velocities. All study procedures were approved by the Institutional Review Board at the Hunter Holmes McGuire VA Medical Center, USA(IRB #: 02314) on May 3, 2017.     

Evaluation of muscles affected by myositis using magnetic resonance elastography

Introduction: Idiopathic inflammatory myopathies (IIMs, or myositis) represent a group of autoimmune diseases that result in decreased muscle strength and/or endurance. Non‐invasive tools to assess muscle may improve our understanding of the clinical and functional consequences of myopathies and their response to treatment. In this study we examine magnetic resonance elastography (MRE), a non‐invasive technique that assesses the shear modulus (stiffness) of muscle, in IIM subjects. Methods: Nine subjects with active myositis completed the MRE protocol. Participants lay in a positioning device, and scans of the vastus medialis (VM) were taken in the relaxed state and at two contraction levels. Manual inversion was used to estimate the stiffness. Results: A significant reduction in muscle stiffness was seen in myositis subjects compared with healthy controls during the “relaxed” condition. Discussion: The use of non‐invasive technologies such as MRE may provide greater understanding of the pathophysiology of IIM and improve assessment of treatment efficacy. Muscle Nerve, 2011     

Muscle velocity recovery cycles: Comparison between surface and needle recordings

Introduction: Recording of muscle velocity recovery cycles (MVRCs) has been developed as a technique to investigate the pathophysiology of muscle diseases. MVRCs have been measured by direct muscle stimulation and concentric electromyographic needle recording. This study was undertaken to determine whether recordings can be made with surface electrodes. Methods: MVRCs with 1 and 2 conditioning stimuli were recorded simultaneously with concentric needle and surface electrodes from the brachioradialis muscle in 12 healthy volunteers. Muscle relative refractory period, early and late supernormality, and extra‐late supernormality were compared between the recording techniques. Results: Surface recordings were possible in all subjects. The multifiber action potentials recorded with surface electrodes were smaller than those recorded with needles, but there was no significant difference between any of their MVRC properties. Conclusions: MVRCs can be recorded with surface electrodes in healthy subjects. The use of surface electrodes may facilitate the technique of recording MVRCs. Muscle Nerve 53: 205–208, 2016     

The relationship between passive stiffness and muscle power output: Influence of muscle cross‐sectional area normalization

Introduction: We examined the relationship between passive stiffness of posterior hip and thigh muscles and muscle power output before and after normalization of passive stiffness to muscle cross‐sectional area (CSA). Methods: Pearson correlation coefficients (r) were used to assess the relationships between the normalized and non‐normalized slopes of the initial (phase 1) and final (phase 2) portions of the angle–torque curve and peak power output (Pmax). Results: A significant positive relationship was observed between the non‐normalized slope of phase 1 and Pmax (r = 0.723; P ≤ 0.001); however, no correlations were observed between the normalized slope of phase 1 and Pmax (r = 0.244; P = 0.299) nor between Pmax and the normalized and non‐normalized slopes of phase 2 (r = ?0.159–0.418; P = 0.067–0.504). Conclusions: The findings suggest that muscle size, rather than stiffness, accounted for a significant portion of the variance in muscle power output. Muscle Nerve 49 : 69–75, 2014     

Caffeine improves neuromuscular function during maximal dynamic exercise

Introduction: In this study we tested the hypothesis that caffeine supplementation improves neuromuscular function, which has both nutritional and clinical relevance. Methods: Fourteen male subjects (mean ± SD: 23.8 ± 2.8 years) volunteered in a double‐blind, repeated‐measures study with placebo (PLA) or caffeine (CAFF) (6 mg kg^?1). Maximal voluntary isometric contractions (MVCs), evoked maximal twitch, and maximal isokinetic contractions during elbow flexion were assessed. Mechanical and electromyographic (EMG) signals from the biceps brachii muscle were recorded, and muscle fiber conduction velocity (CV) was calculated to evaluate changes in the muscle force–velocity relationship and muscle fiber recruitment. Results: The torque–angular velocity curve was enhanced after CAFF supplementation. This was supported by a concomitant increase of CV values (8.7% higher in CAFF). Conclusions: Caffeine improves muscle performance during short‐duration maximal dynamic contractions. The concomitant improvement of mean fiber CV supports the hypothesis of an effect of caffeine on motor unit recruitment. Muscle Nerve, 2011.     

Passive properties of the muscle‐tendon unit: The influence of muscle cross‐sectional area

The purpose of the present study was to examine the relationships among the passive properties of the muscle–tendon unit and muscle cross‐sectional area (CSA). Our findings indicated significant relationships between muscle CSA and passive stiffness (P < 0.05; r = 0.830) and muscle CSA and passive energy absorption (P < 0.05; r = 0.765). Since passive stiffness and the ability to absorb passive energy decreases with many diseases, these findings may support the need to maintain or increase muscle CSA. Muscle Nerve 39: 227–229, 2009     

Assessment of musculo‐articular and muscle stiffness in young and older men

Introduction: The aim of this cross‐sectional study was to concurrently assess musculo‐articular stiffness (MAS) and muscle stiffness (MS) of the knee extensors in younger and older individuals. Methods: Fourteen young (22.1 ± 3.0 years old) and 12 older (65.4 ± 5.7 years old) men were tested for maximal voluntary contraction (MVC), rate of torque development (RTD), muscle thickness, MAS, and MS of knee extensors. Results: MVC, RTD, and muscle thickness were higher in the younger group (288.6 vs. 194.3 Nm, 1319.5 vs. 787.0 Nm s^?1, 23.1 vs. 17.7 mm, respectively, P < 0.05). MAS normalized to the load supported (30% of MVC) was not different between groups (87.9 vs. 88.5 Nm^?1kg^?1), whereas the older group exhibited a higher level of normalized MS (23.2 vs. 18.6 Nm^?1kg^?1, P < 0.05). Conclusions: Determinants of MS have been highlighted along with their role in elevated MS. The unaltered level of MAS, which is functionally important in an aging population, might be achieved through a decrease in tendon stiffness. Muscle Nerve 46: 559–565, 2012     

Myotonia associated with caveolin-3 mutation

Introduction: Caveolin‐3 is a major component of the caveolae in skeletal and cardiac muscle.Mutations in the caveolin‐3 gene (CAV3) lead to a spectrum of clinical phenotypes including limb‐girdle muscular dystrophy 1C, distal myopathy, rippling muscle disease, isolated hyperCKemia, and cardiomyopathy. Case Report: A 24‐year‐old man with myalgia, muscle stiffness, and fatigue has normal strength and prominent myotonic discharges in the gastrocnemius. He also has epilepsy. He harbors a heterozygous CAV3 mutation, p.V57M. He has no mutations in CLCN1 and SCN4A, and he had normal genetic testing for myotonic dystrophy type 1 and type 2. Conclusions: Mutations in CAV3, and in particular p.V57M in CAV3, previously reported in isolated familial hyperCKemia, can be associated with electrical myotonia. Muscle Nerve 45: 897‐900, 2012     

Sarcolemmal excitability changes in normal human aging

Introduction: The exact mechanisms underlying the loss of skeletal muscle bulk and power with normal human aging are not well established. Recording of muscle velocity recovery cycles (MVRCs) is an in‐vivo neurophysiologic technique we employed to assess the impact of age on sarcolemmal excitability. Methods: MVRC recordings were obtained from tibialis anterior (n = 74) and rectus femoris (n = 32) muscles in 74 healthy subjects (18–84 years, median age 35 years, interquartile range 29–55 years). Results: Increasing age was linearly associated with longer muscle relative refractory period (MRRP) and reduced early supernormality (ESN) in both tibialis anterior (MRRP: r² = 0.38, P < 0.001; ESN: r² = 0.33, P < 0.001) and rectus femoris (MRRP: r² = 0.30, P = 0.002; ESN: r² = 0.19, P = 0.01) muscles. Discussion: The results are consistent with progressive depolarization of the resting sarcolemmal potential with normal aging. This may be an important mechanism in explaining age‐related muscle decline. Muscle Nerve 57 : 981–988, 2018     

Whole‐body magnetic resonance imaging evaluation of facioscapulohumeral muscular dystrophy

Introduction: Facioscapulohumeral muscular dystrophy (FSHD) is a hereditary disorder that causes progressive muscle wasting. Increasing knowledge of the pathophysiology of FSHD has stimulated interest in developing biomarkers of disease severity. Methods: Two groups of MRI scans were analyzed: whole‐body scans from 13 subjects with FSHD; and upper and lower extremity scans from 34 subjects with FSHD who participated in the MYO‐029 clinical trial. Muscles were scored for fat infiltration and edema‐like changes. Fat infiltration scores were compared with muscle strength and function. Results: The analysis revealed a distinctive pattern of both frequent muscle involvement and frequent sparing in FSHD. Averaged fat infiltration scores for muscle groups in the legs correlated with quantitative muscle strength and 10‐meter walk times. Conclusions: Advances in MRI technology allow for acquisition of rapid, high‐quality, whole‐body imaging in diffuse muscle disease. This technique offers a promising disease biomarker in FSHD and other muscle diseases. Muscle Nerve 52: 512–520, 2015     

Effect of caffeine ingestion on torque and muscle activity during resistance exercise in men

Introduction: We examined the effect of caffeine ingestion on muscle torque production and muscle activity at different contraction speeds in trained men. Methods: 10 men (mean age ± SD = 22 ± 1.1 years) volunteered to participate. A double‐blind, randomized cross‐over design was used. Sixty minutes postingestion of caffeine (6 mg kg^?1) or placebo, participants completed 6 repetitions of isokientic knee extension at 3 angular velocities (30°s^?1, 150°s^?1, 300°s^?1) from which peak torque was determined. Electromyographic activity of the vastus medialis was also collected. Results: Repeated measures analysis of variance indicated that muscle torque production was significantly higher (P = 0.02) with caffeine compared with placebo. A significant (P = 0.02) substance by velocity interaction for muscle activity indicated significantly higher vastus medialis muscle activity in the presence of caffeine versus placebo, and this difference was amplified as angular velocity increased. Conclusions: Acute caffeine ingestion improves muscle performance and increases muscle activity during short‐duration maximal dynamic contractions. Muscle Nerve 50: 523–527, 2014     

Rapid high‐amplitude circumferential slow wave propagation during normal gastric pacemaking and dysrhythmias

Background Gastric slow waves propagate aborally as rings of excitation. Circumferential propagation does not normally occur, except at the pacemaker region. We hypothesized that (i) the unexplained high‐velocity, high‐amplitude activity associated with the pacemaker region is a consequence of circumferential propagation; (ii) rapid, high‐amplitude circumferential propagation emerges during gastric dysrhythmias; (iii) the driving network conductance might switch between interstitial cells of Cajal myenteric plexus (ICC‐MP) and circular interstitial cells of Cajal intramuscular (ICC‐IM) during circumferential propagation; and (iv) extracellular amplitudes and velocities are correlated. Methods An experimental–theoretical study was performed. High‐resolution gastric mapping was performed in pigs during normal activation, pacing, and dysrhythmia. Activation profiles, velocities, and amplitudes were quantified. ICC pathways were theoretically evaluated in a bidomain model. Extracellular potentials were modeled as a function of membrane potentials. Key Results High‐velocity, high‐amplitude activation was only recorded in the pacemaker region when circumferential conduction occurred. Circumferential propagation accompanied dysrhythmia in 8/8 experiments was faster than longitudinal propagation (8.9 vs 6.9 mm s^?1; P = 0.004) and of higher amplitude (739 vs 528 μV; P = 0.007). Simulations predicted that ICC‐MP could be the driving network during longitudinal propagation, whereas during ectopic pacemaking, ICC‐IM could outpace and activate ICC‐MP in the circumferential axis. Experimental and modeling data demonstrated a linear relationship between velocities and amplitudes (P < 0.001). Conclusions & Inferences The high‐velocity and high‐amplitude profile of the normal pacemaker region is due to localized circumferential propagation. Rapid circumferential propagation also emerges during a range of gastric dysrhythmias, elevating extracellular amplitudes and organizing transverse wavefronts. One possible explanation for these findings is bidirectional coupling between ICC‐MP and circular ICC‐IM networks.     

Quantitative neuromuscular ultrasound in the intensive care unit

Introduction: Intensive care unit acquired weakness (ICU‐AW) results from a complex mixture of nerve and muscle pathology, and early identification is challenging. This pilot study was designed to examine the ultrasonographic changes that occur in muscles during ICU hospitalization. Methods: Patients admitted to the ICU for acute respiratory failure were enrolled prospectively and underwent serial muscle ultrasound for thickness and gray‐scale assessment of the tibialis anterior, rectus femoris, abductor digiti minimi, biceps, and diaphragm muscles over 14 days. Results: Sixteen participants were enrolled. The tibialis anterior (P = 0.001) and rectus femoris (P = 0.041) had significant decreases in gray‐scale standard deviation when analyzed over 14 days. No muscles showed significant changes in thickness. Conclusions: Ultrasound is an informative technique for assessing muscles of patients in the ICU, and lower extremity muscles demonstrated increased homogeneity during ICU stays. This technique should be examined further for diagnosing and tracking those with ICU‐AW. Muscle Nerve, 2013     

An interactive voice response diary for patients with non-dystrophic myotonia

Introduction: Non‐dystrophic myotonia (NDM) is caused by mutations in muscle chloride and sodium channels. Currently, there is no standardized instrument for documenting symptom frequency and severity in NDM. Methods: Subjects used an automated, interactive, telephone‐based voice response diary (IVR) to record frequency and severity of stiffness, weakness, pain, and tiredness once a week for 8 weeks, after their baseline visits. Results: We describe the IVR and report data on 76 subjects for a total of 385 person‐weeks. Overall there were 5.1 calls per subject. Forty‐eight subjects called in 5 or more times, and 14 called in 8 times. Stiffness was both the most frequent and severe symptom. Warm‐up and handgrip myotonia were associated with higher severity scores for stiffness. Conclusions: IVR is a convenient technology to allow patient reporting of repeated and real‐time symptom frequency and severity, and it is presently being used in a trial of mexiletine in NDM. Muscle Nerve 44: 30–35, 2011     

A marginal level of dystrophin partially ameliorates hindlimb muscle passive mechanical properties in dystrophin‐null mice

Introduction: The goal of this study was to determine whether a minimal level of dystrophin expression improves the passive mechanical properties of skeletal muscle in the murine Duchenne muscular dystrophy model. Methods: We compared the elastic and viscous properties of the extensor digitorum longus muscle (EDL) in mdx3cv and mdx4cv mice at 6, 14, and 20 months of age. Both strains are on the C57Bl/6 background, and both lose the full‐length dystrophin protein. Interestingly, mdx3cv mice express a near full‐length dystrophin at ∽5% of the normal level. Results: We found that the stress–strain profile and the stress relaxation rate of the EDL in mdx3cv mice were partially preserved in all age groups compared with age‐matched mdx4cv mice. Conclusion: Our results suggest that a low level of dystrophin expression may treat muscle stiffness in Duchenne muscular dystrophy. Muscle Nerve, 2012     

Whole‐body high‐field MRI shows no skeletal muscle degeneration in young patients with recessive myotonia congenita

Kornblum C, Lutterbey GG, Czermin B, Reimann J, von Kleist‐Retzow J‐C, Jurkat‐Rott K, Wattjes MP. Whole‐body high‐field MRI shows no skeletal muscle degeneration in young patients with recessive myotonia congenita.
Acta Neurol Scand: 2010: 121: 131–135.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Background – Muscle magnetic resonance imaging (MRI) is the most sensitive method in the detection of dystrophic and non‐dystrophic abnormalities within striated muscles. We hypothesized that in severe myotonia congenita type Becker muscle stiffness, prolonged transient weakness and muscle hypertrophy might finally result in morphologic skeletal muscle alterations reflected by MRI signal changes. Aim of the study – To assess dystrophic and/or non‐dystrophic alterations such as fatty or connective tissue replacement and muscle edema in patients with severe recessive myotonia congenita. Methods – We studied three seriously affected patients with myotonia congenita type Becker using multisequence whole‐body high‐field MRI. All patients had molecular genetic testing of the muscle chloride channel gene (CLCN1). Results – Molecular genetic analyses demonstrated recessive CLCN1 mutations in all patients. Two related patients were compound heterozygous for two novel CLCN1 mutations, Q160H and L657P. None of the patients showed skeletal muscle signal changes indicative of fatty muscle degeneration or edema. Two patients showed muscle bulk hypertrophy of thighs and calves in line with the clinical appearance. Conclusions – We conclude that (i) chloride channel dysfunction alone does not result in skeletal muscle morphologic changes even in advanced stages of myotonia congenita, and (ii) MRI skeletal muscle alterations in myotonic dystrophy must be clear consequences of the dystrophic disease process.     

Chloride channels in myotonia congenita assessed by velocity recovery cycles

Introduction: Myotonia congenita (MC) is caused by congenital defects in the muscle chloride channel CLC‐1. This study used muscle velocity recovery cycles (MVRCs) to investigate how membrane function is affected. Methods: MVRCs and responses to repetitive stimulation were compared between 18 patients with genetically confirmed MC (13 recessive, 7 dominant) and 30 age‐matched, normal controls. Results: MC patients exhibited increased early supernormality, but this was prevented by treatment with sodium channel blockers. After multiple conditioning stimuli, late supernormality was enhanced in all MC patients, indicating delayed repolarization. These abnormalities were similar between the MC subtypes, but recessive patients showed a greater drop in amplitude during repetitive stimulation. Conclusions: MVRCs indicate that chloride conductance only becomes important when muscle fibers are depolarized. The differential responses to repetitive stimulation suggest that, in dominant MC, the affected chloride channels are activated by strong depolarization, consistent with a positive shift of the CLC‐1 activation curve. Muscle Nerve 49 : 845–857, 2014