Quantitative muscle ultrasound versus quantitative magnetic resonance imaging in facioscapulohumeral dystrophy

Introduction: Ultrasound and magnetic resonance imaging (MRI) are non‐invasive methods that can be performed repeatedly and without discomfort. In the assessment of neuromuscular disorders it is unknown if they provide complementary information. In this study we tested this for patients with facioscapulohumeral muscular dystrophy (FSHD). Methods: We performed quantitative muscle ultrasound (QMUS) and quantitative MRI (QMRI) of the legs in 5 men with FSHD. Results: The correlation between QMUS‐determined z‐scores and QMRI‐determined muscle fraction and T1 signal intensity (SI) was very high. QMUS had a wider dynamic range than QMRI, whereas QMRI could detect inhomogeneous distribution of pathology over the length of the muscles. Conclusions: Both QMUS and QMRI are well suited for imaging muscular dystrophy. The wider dynamic range of QMUS can be advantageous in the follow‐up of advanced disease stages, whereas QMRI seems preferable in pathologies such as FSHD that affect deep muscle layers and show inhomogeneous abnormality distributions. Muscle Nerve 50: 968–975, 2014     

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     

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     

Efficacy and safety of creatine supplementation in juvenile dermatomyositis: A randomized,double‐blind,placebo‐controlled crossover trial

Introduction: It has been suggested that creatine supplementation is safe and effective for treating idiopathic inflammatory myopathies, but no pediatric study has been conducted to date. The objective of this study was to examine the efficacy and safety of creatine supplementation in juvenile dermatomyositis (JDM) patients. Methods: In this study, JDM patients received placebo or creatine supplementation (0.1 g/kg/day) in a randomized, crossover, double‐blind design. Subjects were assessed at baseline and after 12 weeks. The primary outcome was muscle function. Secondary outcomes included body composition, aerobic conditioning, health‐related quality of life, and muscle phosphocreatine (PCr) content. Safety was assessed by laboratory parameters and kidney function measurements. Results: Creatine supplementation did not affect muscle function, intramuscular PCr content, or any other secondary outcome. Kidney function was not affected, and no side effects were reported. Conclusions: Twelve weeks of creatine supplementation in JDM patients were well‐tolerated and free of adverse effects, but treatment did not affect muscle function, intramuscular PCr, or any other parameter. Muscle Nerve 53 : 58–66, 2016     

Quantitative gray‐scale analysis in skeletal muscle ultrasound: A comparison study of two ultrasound devices

Muscle ultrasound is a useful technique to detect neuromuscular disorders. Quantification of muscle echo intensity (EI) using gray‐scale analysis is more reliable and more sensitive compared with visual evaluation of the images. We devised a method to reliably use EI normal values established with one ultrasound device for use with another device. Based on measurements in a dedicated phantom and in 7 healthy subjects, a conversion equation was calculated to convert the mean EI. The reliability of this equation was next evaluated in a follow‐up study of 22 healthy children. Mean muscle EI could be reliably converted from one ultrasound device to another. This allows for normal values obtained with one device to be used with other devices, which is an important step forward toward the use of quantitative muscle ultrasound in daily clinical care. Muscle Nerve, 2009     

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     

Serum brain‐derived neurotrophic factor and interleukin‐6 response to high‐volume mechanically demanding exercise

Introduction: The aim of this study was to follow circulating brain‐derived neurotrophic factor (BDNF) and interleukin‐6 (IL‐6) levels in response to severe muscle‐damaging exercise. Methods: Young healthy men (N = 10) performed a bout of mechanically demanding stretch–shortening cycle exercise consisting of 200 drop jumps. Voluntary and electrically induced knee extension torque, serum BDNF levels, and IL‐6 levels were measured before and for up to 7 days after exercise. Results: Muscle force decreased by up to 40% and did not recover by 24 hours after exercise. Serum BDNF was decreased 1 hour and 24 hours after exercise, whereas IL‐6 increased immediately and 1 hour after but recovered to baseline by 24 hours after exercise. IL‐6 and 100‐Hz stimulation torque were correlated (r = ?0.64, P < 0.05) 24 hours after exercise. Discussion: In response to acute, severe muscle‐damaging exercise, serum BDNF levels decrease, whereas IL‐6 levels increase and are associated with peripheral fatigue. Muscle Nerve 57 : E46–E51, 2018     

Ultrasound characterization of medial gastrocnemius tissue composition in children with spastic cerebral palsy

Introduction: In this study we aimed to characterize muscle composition of the medial gastrocnemius in children with spastic cerebral palsy (SCP) using quantitative ultrasound. Methods: Forty children with SCP, aged 4–14 years, participated in this study. Children were grouped according to the gross motor function classification system (GMFCS I–V) and compared with a cohort of age‐ and gender‐matched, typically developing children (TD; n = 12). Ultrasound scans were taken of the medial gastrocnemius. Images were then characterized using grayscale statistics to determine mean echo intensity (EI) and the size and number of spatially connected homogeneous regions (i.e., blobs). Results: Significant differences in skeletal muscle composition were found between children with SCP and their TD peers. Children classified as GMFCS III consistently exhibited the highest EI and blob area. Conclusions: This study demonstrates altered tissue composition in children with SCP visualized using ultrasound. Further work is required to determine the pathophysiology contributing to these alterations in SCP. Muscle Nerve 52:397–403, 2015     

Longitudinal 2‐point dixon muscle magnetic resonance imaging in becker muscular dystrophy

Introduction: Quantitative MRI techniques detect disease progression in myopathies more sensitively than muscle function measures or conventional MRI. To date, only conventional MRI data using visual rating scales are available for measurement of disease progression in Becker muscular dystrophy (BMD). Methods: In 3 patients with BMD (mean age 36.8 years), the mean fat fraction (MFF) of the thigh muscles was assessed by MRI at baseline and at 1‐year follow‐up using a 2‐point Dixon approach (2PD). The motor function measurement scale (MFM) was used for clinical assessment. Results: The mean MFF of all muscles at baseline was 61.6% (SD 7.6). It increased by 3.7% to 65.3% (SD 4.7) at follow‐up. The severity of muscle involvement varied between various muscle groups. Conclusions: As in other myopathies, 2PD can quantify fatty muscle degeneration in BMD and can detect disease progression in a small sample size and at relatively short imaging intervals. Muscle Nerve 51 : 918–921, 2015     

Vastus lateralis exhibits non‐homogenous adaptation to resistance training

Introduction: Variations in transverse point of measure on the vastus lateralis (VL) may significantly affect the relationship between structure and function. The purpose of this study was to compare changes in muscle architecture at 2 commonly used points of measure (VL0 and VL5). Methods: Maximal strength (1‐repetition maximum [1RM] barbell squat) and muscle architecture were assessed PRE and POST 15 weeks of periodized resistance training. VL0 was 50% of the straight line distance between the greater trochanter and lateral epicondyle of the femur. VL5 was 5cm medial to VL0. Results: Increases in 1RM strength (3.7 ± 2.4 kg; P = 0.004) were observed. Changes in muscle thickness (MT) at VL5 were significantly greater than at VL0 (P = 0.006). Changes in strength correlated with changes in muscle architecture at VL0 only (MT: r = 0.561; fascicle length: r = 0.503). Conclusions: Changes in muscle architecture appear to occur in a non‐homogeneous manner. Muscle Nerve 50 : 785–793, 2014     

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     

Muscle magnetic resonance imaging and histopathology in ACTA1‐related congenital nemaline myopathy

Introduction: Muscle biopsy is usually diagnostic in nemaline myopathy (NM), but some patients may show nonspecific findings, leading to pitfalls in diagnosis. Muscle MRI is a helpful complementary tool. Methods: We assessed the clinical, histopathological, MRI, and molecular findings in a 19‐year‐old patient with NM in whom 2 muscle biopsies with ultrastructural examination showed no nemaline bodies. We analyzed the degree and pattern of muscle MRI involvement of the entire body, including the tongue and pectoral muscles. Results: Muscle MRI abnormalities in sartorius, adductor magnus, and anterior compartment muscles of the leg suggested NM. A previously unreported fatty infiltration of the tongue was found. A third biopsy after the muscle MRI showed scant nemaline bodies. A novel heterozygous de novo ACTA1 c.611C>T/p.Thr204Ile mutation was detected. Conclusions: We highlight the contribution of muscle imaging in addressing the genetic diagnosis of ACTA1‐related NM. Muscle Nerve 50: 1011–1016, 2014     

Thigh magnetic resonance imaging for the evaluation of disease activity in patients with idiopathic inflammatory myopathies followed in a single center

Introduction: In patients with idiopathic inflammatory myopathies (IIM), magnetic resonance imaging (MRI) has been proposed as a useful tool for diagnosis and follow‐up. It may identify muscle inflammation (edema) and fatty infiltration for evaluation of disease activity and damage. Little information is available on the role of MRI in assessment of large cohorts of adult patients with IIM. Methods: Fifty‐one patients underwent MRI of the thigh muscles, laboratory tests, and clinical evaluation, including Physician Global Assessment (PGA) of myositis activity and the Manual Muscle Test 8 (MMT8). Results: Muscle edema correlated significantly with creatine kinase values (P = 0.017) and PGA (P < 0.001). A significant correlation between edema and MMT8 values (P = 0.025) was observed when patients with muscle fatty infiltration were excluded. With respect to clinical diagnosis, the sensitivity of MRI was 92.3%, and specificity was 83.3%. Conclusions: MRI appears to provide additional information that complements clinical and biochemical examinations. Muscle Nerve 54 : 666–672, 2016     

Muscle magnetic resonance imaging abnormalities in X‐linked myopathy with excessive autophagy

Introduction: X‐linked myopathy with excessive autophagy (XMEA) is an X‐linked recessive myopathy due to recently reported mutations in the VMA21 gene. Methods: Four men from 2 separate families were studied. The clinical presentation, genetic data, muscle biopsy, and muscle MRI were analyzed. Results: A known VMA21 mutation, c.163+4A>G, and a new mutation, c.163+3A>G, respectively, were found in the 2 families. The clinical course was characterized by onset in childhood and progressive muscle weakness with a limb‐girdle pattern. Muscle biopsy revealed a mild myopathy with an increased number of giant autophagic vacuoles. Whole‐body muscle MRI showed that pelvic girdle and proximal thighs were the most and earliest affected territories, with sparing of rectus femoris muscles. Muscle changes essentially consisted of degenerative fatty replacement. Conclusions: This study highlights a distinctive MRI pattern of muscle involvement, which can be helpful for diagnosis of XMEA, even before muscle biopsy or genetic analysis. Muscle Nerve 52: 673–680, 2015     

Qualitative and quantitative skeletal muscle ultrasound in late-onset acid maltase deficiency

Introduction: Acid maltase deficiency (AMD, or Pompe disease) is an inherited myopathic disorder of glycogen degradation. Diagnosis is often delayed. Muscle ultrasound could improve diagnosis. Methods: We compared skeletal muscle ultrasound images from adults with AMD (n = 10) to other myopathies (n = 81) and, in AMD, compared qualitative (Heckmatt) and quantitative (backscatter) ultrasound measurements with strength and function. Results: Qualitative ultrasound was abnormal in at least one muscle in all AMD subjects. Ultrasound patterns specific for AMD were: normal triceps brachii despite abnormalities in elbow flexors (89% vs. 17%, P < 0.0001); focal abnormalities affecting deep more than superficial biceps brachii (40% vs. 4%, P = 0.002); and more severe involvement of vastus intermedius than rectus femoris (40 vs. 11%, P = 0.03). In AMD, both qualitative (Heckmatt) and quantitative (backscatter) ultrasound measures increased with decreasing strength and function. Conclusions: Muscle ultrasound identifies the presence and specific patterns of AMD pathology, measures disease severity, and can help in the diagnosis of AMD. Muscle Nerve 44: 418–423, 2011     

Proteomic analysis of mouse soleus muscles affected by hindlimb unloading and reloading

Introduction: Disuse muscle atrophy, induced by prolonged space flight, bed rest, or denervation, is a common process with obvious changes in slow‐twitch soleus muscles. Methods: Proteomic analysis was performed on mouse soleus subjected to hindlimb unloading (HU) and hindlimb reloading (HR) to identify new dysregulated proteins. Results: Following HU, the mass and cross‐sectional area of muscle fibers decreased, but they recovered after HR. Proteomic analyses revealed 9 down‐regulated and 7 up‐regulated proteins in HU, and 2 down‐regulated and 5 up‐regulated proteins in HR. The dysregulated proteins were mainly involved in energy metabolism, protein degradation, and cytoskeleton stability. Among the dysregulated proteins were fatty acid binding protein 3, α‐B crystalline, and transthyretin. Conclusions: These results indicate that muscle atrophy induced by unloading is related to activation of proteolysis, metabolic alterations toward glycolysis, destruction of myofibrillar integrity, and dysregulation of heat shock proteins (HSPs). The dysregulated proteins may play a role in muscle atrophy and the recovery process. Muscle Nerve 52 : 803–811, 2015     

Combining MRI and muscle biopsy improves diagnostic accuracy in subacute‐onset idiopathic inflammatory myopathy

Introduction: In 10–20% of patients with subacute‐onset idiopathic inflammatory myopathy (IIM), muscle biopsy is normal or shows nonspecific findings. MRI can be used as a triage test before muscle biopsy and as an add‐on test if the biopsy is nondiagnostic. Methods: MRI scans of skeletal muscles and muscle biopsies were evaluated prospectively in 48 patients suspected to have IIM. The interpretations of MRI and muscle biopsy were compared with the definite diagnosis (based on European Neuromuscular Centre criteria and response to corticosteroids). Results: The false negative rate (FNR) of all muscle biopsies was 0.23. Biopsies of a muscle showing hyperintensity on MRI (as triage test) had an FNR of 0.19. The result of MRI as an add‐on test in patients with a nondiagnostic muscle biopsy decreased the FNR from 0.23 to 0.06. Conclusions: We recommend both MRI and muscle biopsy in patients suspected of having IIM. Muscle Nerve 51 : 253–258, 2015     

Neurologic examination and instrument‐based measurements in the evaluation of ulnar neuropathy at the elbow

Introduction: The aim of the study was to compare the utility of instrument‐based assessment of peripheral nerve function with the neurologic examination in ulnar neuropathy at the elbow (UNE). Methods: We prospectively recruited consecutive patients with suspected UNE, performed a neurologic examination, and performed instrument‐based measurements (muscle cross‐sectional area by ultrasonography, muscle strength by dynamometry, and sensation using monofilaments). Results: We found good correlations between clinical estimates and corresponding instrument‐based measurements, with similar ability to diagnose UNE and predict UNE pathophysiology. Discussion: Although instrument‐based methods provide quantitative evaluation of peripheral nerve function, we did not find them to be more sensitive or specific in the diagnosis of UNE than the standard neurologic examination. Likewise, instrument‐based methods were not better able to differentiate between groups of UNE patients with different pathophysiologies. Muscle Nerve 57 : 951–957, 2018