Shear wave velocity is sensitive to changes in muscle stiffness that occur independently from changes in force.

Clinical assessments for many musculoskeletal disorders involve evaluation of muscle stiffness, although it is not yet possible to obtain quantitative estimates from individual muscles. Ultrasound elastography can be used to estimate the material properties of unstressed, homogeneous, and isotropic materials by tracking the speed of shear wave propagation; these waves propagate faster in stiffer materials. Although elastography has been applied to skeletal muscle, there is little evidence that shear wave velocity (SWV) can directly estimate muscle stiffness since this tissue violates many of the assumptions required for there to be a direct relationship between SWV and stiffness. The objective of this study was to evaluate the relationship between SWV and direct measurements of muscle force and stiffness in contracting muscle. Data were collected from six isoflurane-anesthetized cats. We measured the short-range stiffness in the soleus via direct mechanical testing in situ and SWV via ultrasound imaging. Measurements were taken during supramaximal activation at optimum muscle length, with muscle temperature varying between 26°C and 38°C. An increase in temperature causes a decrease in muscle stiffness at a given force, thus decoupling the tension-stiffness relationship normally present in muscle. We found that increasing muscle temperature decreased active stiffness from 4.0 ± 0.3 MPa to 3.3 ± 0.3 MPa and SWV from 16.9 ± 1.5 m/s to 15.9 ± 1.6 m/s while force remained unchanged (mean ± SD). These results demonstrate that SWV is sensitive to changes in muscle stiffness during active contractions. Future work is needed to determine how this relationship is influenced by changes in muscle structure and tension.NEW & NOTEWORTHY Shear wave ultrasound elastography is a noninvasive tool for characterizing the material properties of muscle. This study is the first to compare direct measurements of stiffness with ultrasound measurements of shear wave velocity (SWV) in a contracting muscle. We found that SWV is sensitive to changes in muscle stiffness, even when controlling for muscle tension, another factor that influences SWV. These results are an important step toward developing noninvasive tools for characterizing muscle structure and function.

Imaging alterations in skeletal muscle channelopathies: a study in 15 patients.

Skeletal muscle channelopathies (SMC), including non dystrophic myotonias (NDM) and periodic paralyses (PP), are characterized by considerable clinical overlap and clinical features not always allow addressing molecular diagnosis. Muscle imaging has been shown to be useful for differential diagnosis in neuromuscular disorders, however it has been relatively poorly investigated in SMC. We studied 15 patients affected by genetically confirmed SMC (NDM = 9, PP = 6) through muscle MRI or CT of thighs and legs, including 11 patients mutated in SCN4A gene, 2 in CACNA1S and 2 in CLCN1. Mean age at muscle imaging was 45.2 ± 18 years (range 22-70). Overall, fatty infiltration was found in thigh muscles in 8 (53%) patients and in leg muscles in 10 (60%). All patients mutated in CLCN1 and CACNA1S had abnormal thigh and/or leg muscle MRI, regardless the disease duration. On the contrary normal thigh and leg muscle MRI or CT scans were observed in 4/15 (27%) patients, all mutated in SCN4A. Variable degrees of fatty changes were found in patients mutated in SCN4A, CACNA1S and CLCN1. No differences on overall score of fatty infiltration were detected between NDM and PP (p-value = 0.953) neither between presence or absence of permanent weakness (p-value = 0.951). Our data confirm the presence of muscle fatty changes in the majority of SMC patients, although without any specific pattern of involvement. However muscle MRI may be a useful tool for longitudinal follow-up of SMC patients, in particular to evaluate the occurrence and the progression of fixed myopathy.

Skeletal muscle involvement in myotonic dystrophy type 2. A comparative muscle ultrasound study.

This study determines the presence and extent of muscle changes in 31 myotonic dystrophy type 2 (DM2) patients detected by muscle ultrasound. Results were compared to 31 adult-onset myotonic dystrophy type 1 patients (DM1) and healthy controls. Furthermore, we tested the hypothesis that structural muscle changes correlate with age, quantitative muscle force and serum creatine kinase in both disorders. In DM2 all seven examined muscles (right masseter muscle, right and left biceps brachii, right and left forearm flexors, right rectus femoris, and left tibialis anterior muscle) showed increased mean echo intensities (p ≤ 0.001). Atrophy of the masseter muscle and rectus femoris were both found in 23% of DM2 patients. Muscle thickness was significantly more decreased in the elbow flexors in DM2 compared to DM1. Echo intensity sum score correlated positively with age in DM2 (r=0.57, p=0.001) and negatively with muscle force (r=0.36, p=0.048). We conclude that all tested muscles are affected and structurally abnormal in DM2 patients. Proximal arm muscles are more affected in DM2 compared to DM1, which corresponds to clinical findings.

Muscle ultrasound measurements and functional muscle parameters in non-dystrophic myotonias suggest structural muscle changes.

Patients with non-dystrophic myotonias, including chloride (myotonia congenita) and sodium channelopathies (paramyotonia congenita/potassium aggravated myotonias), may show muscular hypertrophy in combination with some histopathological abnormalities. However, the extent of muscle changes has never been assessed objectively in a large group genetically confirmed patients. This study quantitatively determines echo intensities, thicknesses, ranges-of-motion and force of four skeletal muscles in 63 genetically confirmed patients. The main findings revealed elevated echo intensities in all muscles except the rectus femoris (+1.3-2.2SD, p<0.0001), and hypertrophy in the arms (+0.5-0.9SD, p<0.01). Muscle echo intensities were inversely correlated to the corresponding ranges-of-motion (biceps brachii: r= -0.43; p<0.001, forearm flexors: r= -0.47; p<0.001, rectus femoris: r= -0.40; p=0.001, and tibial anterior: r= -0.27; p=0.04) and correlated positively to age (r=0.22; p=0.05). The echo intensity of the forearm flexors was inversely correlated to their muscles' force (r= -0.30; p=0.02). Together, these data suggest that non-dystrophic myotonias may lead to structural muscle changes.

Clinical and genetic analysis of a family with PROMM.

PROMM (proximal myotonic myopathy) and DM2 (myotonic dystrophy Type 2) are autosomal dominant multisystem disorders that have both been linked to chromosome 3q. Recently, the genetic basis of DM2 has been defined by a '(CCTG)(n)' expansion mutation in intron 1 of the ZNF9 gene. We identified and studied a multigenerational family in which five members had clinical features consistent with PROMM. Two affected members were available for detailed clinical, electrophysiological, radiological and genetic analysis. Our study confirms that the PROMM phenotype is associated with DM2-(CCTG)(n) expansion mutations. In addition, our results may extend the clinical spectrum of manifestations to include vestibular symptoms.

Executive dysfunction and avoidant personality trait in myotonic dystrophy type 1 (DM-1) and in proximal myotonic myopathy (PROMM/DM-2).

A previous study in proximal myotonic myopathy (PROMM/DM-2) and myotonic dystrophy type 1 (DM-1) using brain positron emission tomography demonstrated a reduced cerebral blood flow in the frontal and temporal regions associated with cognitive impairment. The objective was to investigate further cognitive and behavioural aspects in a new series of patients with DM-1 and PROMM/DM-2. Nineteen patients with genetically determined PROMM/DM-2 and 21 patients with moderately severe DM-1 underwent neuropsychological testing and neuropsychiatric interviews. DM-1 and PROMM/DM-2 patients had significantly lower scores on tests of frontal lobe function compared to controls. Neuropsychiatric interviews demonstrated an avoidant trait personality disorder in both patient groups. Brain single photon emission computed tomography showed frontal and parieto-occipital hypoperfusion. The results suggest that there is a specific cognitive and behavioural profile in PROMM/DM-2 and in DM-1, and that this profile is associated with hypoperfusion in frontal and parieto-occipital regions of the brain.