Exercise induced muscle blood flow is decreased in Charcot–Marie–Tooth disease type 1 polyneuropathy: a power Doppler analysis

Background and purpose

Intramuscular blood flow increases during physical activity and may be quantified immediately following exercise using power Doppler sonography. Post-exercise intramuscular blood flow is reduced in patients with muscular dystrophy, associated with disease severity and degenerative changes. It is not known if intramuscular blood flow is reduced in patients with neuropathy, nor if it correlates with muscle strength and structural changes. The aim was to determine whether blood flow is reduced in patients with polyneuropathy due to Charcot–Marie–Tooth disease type 1 (CMT1) and to compare more affected distal to less affected proximal muscles.

Methods

This was a cross-sectional study including 21 healthy volunteers and 17 CMT patients. Power Doppler ultrasound was used to quantify post-exercise intramuscular blood flow in distal (gastrocnemius) and proximal (elbow flexor) muscles. Intramuscular blood flow was compared to muscle echo intensity, muscle strength, disease severity score, patient age and electromyography.

Results

Polyneuropathy patients showed reduced post-exercise blood flow in both gastrocnemius and elbow flexors compared to controls. A more prominent reduction was seen in the gastrocnemius (2.51% vs. 10.34%, p < 0.0001) than in elbow flexors (4.48% vs. 7.03%, p < 0.0001). Gastrocnemius intramuscular blood flow correlated with muscle strength, disease severity and age. Receiver operating characteristic analysis showed that quantification of intramuscular blood flow was superior to echo intensity for detecting impairment in the gastrocnemius (area under the curve 0.962 vs. 0.738, p = 0.0126).

Conclusion

Post-exercise intramuscular blood flow is reduced in CMT1 polyneuropathy. This reduction is present in both impaired distal and minimally affected proximal muscles, indicating it as an early marker of muscle impairment due to neuropathy.     

Quantitative ultrasound of the tongue and submental muscles in children and young adults

Introduction: The purpose of this study was to assess the feasibility of quantitative muscle ultrasound (QMUS) to visualize oral muscles and to establish normative data for muscle thickness and echo intensity of submental and tongue muscles in healthy children and young adults. The data were compared with those of 5 patients with Duchenne muscular dystrophy (DMD). Methods: Ultrasound images from the suprahyoid region and from the surface of the tongue were made in 53 healthy subjects aged 5 to 30 years. Results: All measurements were feasible in all subjects and patients with good reproducibility except for the mylohyoid muscle. Muscle thickness depended on height, and echo intensity depended on weight. Our findings suggest gradual involvement of oral muscles in DMD. Conclusions: QMUS in oral muscles is feasible in healthy children, adults and patients with DMD. These data show that it is possible to differentiate between healthy persons and patients with DMD. Muscle Nerve 46:31–37, 2012     

Quantitative ultrasonography of facial muscles in patients with chronic facial palsy

Introduction: In this study we introduce quantitative facial muscle ultrasound as a diagnostic tool for patients with chronic unilateral facial palsy. Methods: Muscle area, thickness, and echo intensity of 6 facial muscles (frontalis, orbicularis oculi, orbicularis oris, depressor anguli oris, depressor labii inferioris, and mentalis) and of 2 chewing muscles (temporalis and masseter, as controls) were measured in 20 patients with chronic facial palsy. Results: Aside from 1, all facial muscles were significantly smaller on the paralyzed side. With exception of frontalis and orbicularis oculi muscles, all other facial muscles showed significantly higher echo intensity on the affected side. Muscle size and echo intensity of the chewing muscles showed no side‐to‐side asymmetry. Conclusions: Quantitative ultrasound of facial muscles helps to better characterize their status in patients with chronic facial palsy in the phase of denervation and during regeneration. Muscle Nerve 50 : 358–365, 2014     

A pilot study of neuromuscular ultrasound as a biomarker for amyotrophic lateral sclerosis

Introduction: This study explores the reliability and responsiveness of neuromuscular ultrasound in amyotrophic lateral sclerosis (ALS). Methods: Investigations were conducted with 10 healthy controls, 10 patients with ALS (single point in time), and 10 different patients with ALS (followed over 6 months; 4 completed follow-up). Ultrasound was used to measure the thickness of the geniohyoid, bilateral biceps/brachialis, bilateral tibialis anterior, and bilateral hemidiaphragms (at inspiration and expiration). Interrater and intrarater reliability and change in muscle thickness over 6 months were measured. Results: Interrater correlation coefficients ranged between 0.80 and 0.99 in healthy controls and between 0.78 and 0.97 in patients with ALS. Intrarater correlation coefficients ranged between 0.83 and 0.98 in healthy controls. The mean percentage decline in muscle thickness over 6 months was 20.25%. Discussion: Muscle ultrasound appears to be a reliable technique for measuring important muscles in patients with ALS. Larger studies with age-matched controls should be conducted to assess further the responsiveness of this biomarker in ALS. Muscle Nerve 59 :181–186, 2019     

Quantitative muscle ultrasonography in the follow‐up of juvenile dermatomyositis

Introduction: We explored the use of quantitative muscle ultrasonography (QMUS) for follow‐up of juvenile dermatomyositis (JDM). Methods: Seven JDM patients were evaluated at diagnosis and 1, 3, 6, 12, and 24 months using the Childhood Myositis Assessment Scale (CMAS) and QMUS. Muscle thickness (MT) and quantitative muscle echo intensity (EI) were assessed with QMUS in 4 muscles. Results: Six patients experienced a monocyclic course. At diagnosis EI was slightly increased, and MT was relatively normal. After start of treatment MT first decreased and EI increased, with normalization of EI within 6–12 months (n = 4). One patient had higher EIs at diagnosis and slower normalization, indicating fibrosis, despite early normalization of CMAS. One patient experienced a chronic course, with high EIs and atrophy during follow‐up. Conclusions: QMUS can provide additional information for follow‐up of JDM regarding disease severity and residual muscle damage, particularly after normalization of CMAS. Muscle Nerve 52: 540–546, 2015     

Decomposition-based quantitative electromyography in the evaluation of muscular dystrophy severity

Introduction: Electromyography is useful in the diagnosis of myopathies, but its utility in determining disease severity requires further investigation. In this study we aimed to determine whether decomposition‐based quantitative electromyography (DQEMG) could indicate the severity of involvement in a cohort of patients with muscular dystrophies (MDs). Methods: Fifteen patients with facioscapulohumeral (FSHD), limb‐girdle (LGMD), and Becker (BMD) muscular dystrophy, and 7 healthy controls, participated in this investigation. Knee extensor isometric strength differentiated the “more severe” and “less severe” MD groups. The vastus lateralis (VL), biceps brachii (BB), and tibialis anterior (TA) muscle groups were investigated using DQEMG. Results: All muscles from the MD group showed changes in mean MUP (motor unit potential) AAR (area‐to‐amplitude ratio), and turns, compared with controls (P < 0.05). More severely affected muscles (VL and BB) also had shortened mean MUP durations compared with controls (P < 0.01). Conclusions: DQEMG was capable of indicating the severity of MD involvement, as changes in MUP morphology reflected the progressive nature of the disease. Muscle Nerve, 2012     

Measurement of intramuscular fat by muscle echo intensity

Introduction: The aim of this study was to compare ultrasound echo intensity (EI) with high‐resolution T₁‐weighted MRI and to establish calibration equations to estimate percent intramuscular fat from EI. Methods: Thirty‐one participants underwent both ultrasound and MRI testing of 4 muscles: rectus femoris (RF); biceps femoris (BF); tibialis anterior (TA); and medial gastrocnemius (MG). Results: Strong correlations were found between MRI percent fat and muscle EI after correcting for subcutaneous fat thickness (r = 0.91 in RF, r = 0.80 in BF, r = 0.80 in TA, r = 0.76 in MG). Three types of calibration equations were established. Conclusions: Muscle ultrasound is a practical and reproducible method that can be used as an imaging technique for examination of percent intramuscular fat. Future ultrasound studies are needed to establish equations for other muscle groups to enhance its use in both research and clinical settings. Muscle Nerve 52 : 963–971, 2015     

The magnetic resonance imaging spectrum of facioscapulohumeral muscular dystrophy

Introduction: Facioscapulohumeral muscular dystrophy (FSHD) is associated with a repeat contraction in the D4Z4 gene locus on chromosome 4q35. We used a one‐step quantitative magnetic resonance imaging (MRI) method to evaluate muscle, edema, and fat in patients spanning the range of severity. Methods: Fifteen patients with FSHD were compared with 10 healthy subjects using non‐negative linear least‐squares fitting of 32‐echo relaxation data (T2). The results were compared with a biexponential approach for characterizing muscle/fat ratio and T2 relaxation measurements from fat‐suppressed inversion recovery. Results: Increased T2 signal consistent with edema was common in FSHD subjects, a pattern not present in healthy controls. A varied pattern of edema and fatty replacement in muscles was shown. Conclusions: As a discrete biomarker, edema may be useful for following the clinical course of FSHD. Future work toward optimizing measurement is discussed. Muscle Nerve, 2012     

Quantitative ultrasonography of skeletal muscles in children: normal values

The purpose of this study was to establish normal values of muscle thickness, ratio of muscle thickness to subcutaneous fat thickness, and muscle echo intensity in children between 11 weeks and 16 years of age. Transverse scans of four muscles were made by standardized real-time ultrasound examination. The scans were digitized, and mean echo intensity was measured using gray-scale analysis. A multiple regression equation was used to study which independent parameter (age, height, weight, or sex) influenced the variables for each muscle. Muscle thickness depended on the child's weight. The other parameters did not significantly influence muscle thickness after correction for weight. The ratio of muscle thickness to subcutaneous fat thickness depended on age. Echo intensity showed no correlation with either of the variables. As a result, all normal values, including the equation to calculate them, are described. These normal data may help to determine the diagnostic value of muscle ultrasound in children with suspected neuromuscular disease.     

Skeletal muscle ultrasound

Abstract

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Muscle ultrasound is a convenient technique to visualize normal and pathological muscle tissue as it is non-invasive and real-time. Neuromuscular disorders give rise to structural muscle changes that can be visualized with ultrasound: atrophy can be objectified by measuring muscle thickness, while infiltration of fat and fibrous tissue increases muscle echo intensity, i.e. the muscles become whiter on the ultrasound image. Muscle echo intensity needs to be quantified to correct for age-related increase in echo intensity and differences between individual muscles. This can be done by gray scale analysis, a method that can be easily applied in daily clinical practice. Using this technique, it is possible to detect neuromuscular disorders with predictive values of 90%. Only in young children and metabolic myopathies the sensitivity is lower. Ultrasound is a dynamic technique and therefore capable of visualizing normal and pathological muscle movements. Fasciculations can easily be differentiated from other muscle movements. Ultrasound appeared to be even more sensitive in detecting fasciculations compared to Electromyography (EMG) and clinical observations, because it can visualize a large muscle area and deeper located muscles. With improving resolution and frame rate it has recently become clear that also smaller scale spontaneous muscle activity such as fibrillations can be detected by ultrasound. This opens the way to a broader use of muscle ultrasound in the diagnosis of peripheral nerve and muscle disorders.     

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     

Electrical impedance myography in facioscapulohumeral muscular dystrophy

Introduction: In this study we determined the reliability and validity of electrical impedance myography (EIM) in facioscapulohumeral muscular dystrophy (FSHD). Methods: We performed a prospective study of EIM on 16 bilateral limb and trunk muscles in 35 genetically defined and clinically affected FSHD patients (reliability testing on 18 patients). Summary scores based on body region were derived. Reactance and phase (50 and 100 kHz ) were compared with measures of strength, FSHD disease severity, and functional outcomes. Results: Participants were mostly men, mean age 53.0 years, and included a full range of severity. Limb and trunk muscles showed good to excellent reliability [intraclass correlation coefficients (ICC) 0.72–0.99]. Summary scores for the arm, leg, and trunk showed excellent reliability (ICC 0.89–0.98). Reactance was the most sensitive EIM parameter to a broad range of FSHD disease metrics. Conclusions: EIM is a reliable measure of muscle composition in FSHD that offers the possibility to serially evaluate affected muscles. Muscle Nerve 54 : 696–701, 2016     

Motor function and respiratory capacity in patients with late‐onset pompe disease

Introduction: The relationship between skeletal muscle strength and respiratory dysfunction in Pompe disease has not been examined by quantitative methods. We investigated correlations among lower extremity proximal muscle strength, respiratory function, and motor performance. Methods: Concentric strength of the knee extensor and flexor muscles was measured with a dynamometer, and pulmonary function was evaluated using spirometry in 7 adult patients. The 6‐minute walk test and the 4‐step stair‐climb test were used for assessing aerobic endurance and anaerobic power, respectively. Results: Anaerobic motor performance correlated with strength of both thigh muscles. Respiratory function did not correlate with either muscle strength or motor function performance. Conclusions: Respiratory and lower extremity proximal muscles could be affected differentially by the disease in individual patients. Motor performance is influenced by thigh muscle strength and is less dependent of respiratory capacity in our cohort of ambulatory patients. Muscle Nerve 49:603–606, 2014     

Fatigue resistance of the knee extensor muscles is not reduced in post-polio syndrome

The present study investigated whether intrinsic fatigability of the muscle fibers is reduced in patients with post-polio syndrome (PPS). This may contribute to the muscle fatigue complaints reported by patients with PPS. For this purpose, we assessed contractile properties and fatigue resistance of the knee extensor muscles using repeated isometric electrically evoked contractions in 38 patients with PPS and 19 age-matched healthy subjects. To determine whether any difference in fatigue resistance between both groups could be attributed to differences in aerobic capacity of the muscle fibers, 9 patients with PPS and 11 healthy subjects performed the same protocol under arterial occlusion. Results showed that fatigue resistance of patients with PPS was comparable to that in controls, both in the situation with intact circulation and with occluded blood flow. Together, our findings suggest that there are no differences in contractile properties and aerobic muscle capacity that may account for the increased muscle fatigue perceived in PPS.     

Correlating ultrasound findings of carpal tunnel syndrome with nerve conduction studies

Introduction: The aim of this study was to make correlations between ultrasonographic measurements of thenar muscle and flexor retinaculum and nerve conduction studies (NCS) in carpal tunnel syndrome (CTS). Methods: Ultrasound and NCS were performed on 92 wrists with CTS and on 40 wrists from healthy individuals. Ultrasound of thenar and hypothenar muscles, flexor retinaculum, and median nerve were assessed. The ultrasonographic findings were compared between the 2 groups, and correlation analyses between median latency and ultrasonographic findings were performed. Results: Motor latency correlated positively with flexor retinaculum thickness (FRT) and negatively with the ratio of thenar to hypothenar muscle. FRT and motor latency were found to be increased significantly in CTS. The ratio of thenar to hypothenar muscle was found to be decreased significantly in CTS compared with controls. Conclusions: The ultrasonographic findings of FRT and thenar muscle reflect the severity of disease in patients with CTS and are valuable for the diagnosis of CTS. Muscle Nerve 48 : 905–910, 2013     

Ultrasound appears to be a reliable technique for the diagnosis of piriformis syndrome

Introduction: Piriformis muscle syndrome (PS) is a disorder encompassing a constellation of symptoms, including buttock and hip pain. In this study we aimed to assess the value of ultrasound (US) in the diagnosis of PS. Methods: Thirty-three clinically diagnosed PS patients and 26 healthy volunteers underwent a clinical PS scoring examination and US and MRI assessment of the bilateral piriformis muscles. The areas under the receiver operating characteristic curves (AUROCs) of the US parameters (i.e., increased thickness [iTh] and increased cross-sectional area [iCSA]) for piriformis muscle were evaluated. Results: On US and MRI, the thickness and CSA were increased in PS patients. The AUROCs for the iTh and iCSA for discriminating stage 0 (healthy volunteers) from stage 1 through stage 3 (PS patients) were 0.88 and 0.95, respectively. Discussion: US may be a reliable technique for the clinical diagnosis of PS. Muscle Nerve 59:411–416, 2019     

Minimal training is required to reliably perform quantitative ultrasound of muscle

Introduction: Quantitative ultrasound can measure skeletal muscle pathology. We investigated whether inexperienced evaluators could accurately obtain and analyze ultrasound images. Methods: Two examiners underwent a 20‐minute training session before obtaining ultrasound images of several limb muscles in 21 healthy boys and 19 boys with Duchenne muscular dystrophy (DMD). Gray scale levels (GSLs) of muscle and subcutaneous fat were then measured by 2 analysts: a trained research assistant and a radiologist. We compared results between examiners and analysts. Results: Interrater reliability of muscle GSLs was high between examiners (ICC ≥ 0.85) and analysts (ICC ≥ 0.84). As anticipated, GSLs were higher in dystrophic than in healthy muscles (P < 0.001). Fat GSLs were less reliable (ICC = 0.5–0.89) than muscle and increased with age and body size. Conclusions: GSLs from ultrasound images of healthy and dystrophic skeletal muscle, but not from subcutaneous fat, can be obtained reliably and can be analyzed by inexperienced evaluators with minimal training. Muscle Nerve 50 : 124–128, 2014     

Elevated serum inflammatory markers in post-poliomyelitis syndrome

OBJECTIVES: To determine (i) whether serum inflammatory markers TNFalpha, IL-1beta. IL-6, and leptin are increased in post-poliomyelitis syndrome (PPS) compared to healthy controls; and (ii) whether an association exists between elevated inflammatory markers and clinical parameters in PPS. The cause of PPS is unknown, but abnormal inflammatory responses have been implicated in several small studies. METHODS: Serum inflammatory markers were measured (by Luminex) in 51 PPS patients and 26 normal controls. Clinical parameters assessed included disease duration, muscle strength (Medical Research Council sumscore), fatigue (Fatigue Severity Scale and Multidimensional Fatigue Inventory), and pain (visual analog scale scores). RESULTS: In PPS, TNFalpha levels, as well as IL-6 and leptin were significantly increased compared to controls (Wilcoxon rank-sum test, p=0.03 for TNFalpha, p=0.03 for IL-6, p=0.01 for leptin). The elevated TNFalpha levels in PPS were associated with increased pain due to illness (Spearman correlation coefficient r=0.36, 95% C.I. 0.09 to 0.57) and specifically, with muscle pain (r=0.38, 95% C.I. 0.11 to 0.59). There were no correlations between inflammatory markers in PPS and joint pain, muscle strength, fatigue, or disease duration. CONCLUSIONS: Serum TNFalpha, IL-6 and leptin levels are abnormally increased in PPS patients. Elevated TNFalpha levels appear to be specifically associated with increased muscle pain.     

Contrasting echogenicity in flexor digitorum profundus–flexor carpi ulnaris: A diagnostic ultrasound pattern in sporadic inclusion body myositis

Introduction: In this study we aimed to clarify whether muscle ultrasound (US) of the forearm can be used to differentiate between patients with sporadic inclusion body myositis (s‐IBM) and those with s‐IBM–mimicking diseases. Methods: We compared the echo intensity (EI) of the flexor digitorum profundus (FDP) muscle and the flexor carpi ulnaris (FCU) muscles in patients with s‐IBM (n = 6), polymyositis/dermatomyositis (PM/DM; n = 6), and amyotrophic lateral sclerosis (ALS; n = 6). Results: We identified EI abnormalities in 100% of patients with s‐IBM, 33% of those with PM/DM, and 33% of those with ALS. An “FDP–FCU echogenicity contrast,” a US pattern involving a higher EI in the FDP than in the FCU, was observed in all patients with s‐IBM, but in none of those with PM/DM or ALS. Conclusions: FDP–FCU echogenicity contrast in muscle US is a sensitive diagnostic indicator of s‐IBM. Muscle Nerve 49 : 745–748, 2014     

Quantitative muscle ultrasound is a promising longitudinal follow-up tool in Duchenne muscular dystrophy

Responsive outcome measures are needed to follow the disease status of Duchenne muscular dystrophy (DMD) patients, as new therapeutic approaches become available for affected boys. Quantitative muscle ultrasound (QMUS) is potentially an attractive follow up tool for DMD because it reflects the severity of the dystrophic process without the need for invasive procedures, by quantifying echo intensity (i.e., mean grey level of muscle images) and muscle thickness. We performed a longitudinal follow-up of lower and upper extremity QMUS in 18 DMD patients and compared this with physical functioning in 11 of these patients. QMUS could be performed in every patient, and no patient was subjected to more than a total of 20min of ultrasound scanning time for this study. As expected we found a significant increase of echo intensity with age, reflecting increasing dystrophic muscle changes. This increase was related to ambulatory status, functional grading, muscle strength and motor ability. Our study establishes QMUS as a practical and child-friendly tool for the longitudinal follow up of DMD patients.