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A common animal model of muscle pathology following rotator cuff tear (RCT) is a tenotomy of the supraspinatus and infraspinatus, often combined with neurotomy of the suprascapular nerve, which induces a more robust atrophy response than tenotomy alone. However, the utility of this model depends on its similarity to human muscle pathology post‐RCT, both in terms of the disease phenotype and mechanisms of muscle atrophy and fatty infiltration. Given the clinical prevalence of nerve injury is low and the muscular response to denervation is distinct from mechanical unloading in other models, an understanding of the biological influence of the nerve injury is critical for interpreting data from this RCT model. We evaluated the individual and combined effect of tenotomy and neurotomy across multiple biological scales, in a robust time‐series in the mouse supraspinatus. Muscle composition, histological, and gene expression data related to muscle atrophy, degeneration–regeneration, fatty infiltration, and fibrosis were evaluated. Broadly, we found tenotomy alone caused small, transient changes in these pathological features, which resolved over the course of the study, while neurotomy alone caused a significant fatty atrophy phenotype. The dual injury group had a similar fatty atrophy phenotype to the neurotomy group, though the addition of tenotomy did marginally enhance the fat and connective tissue. Overall, these results suggest the most clinically relevant injury model, tenotomy alone, does not produce a clinically relevant phenotype. The dual injury model partially recapitulates the human condition, but it does so through a nerve injury, which is not well justified clinically. [ABSTRACT FROM AUTHOR]

Introduction/Aims: Duchenne and Becker muscular dystrophies (DMD and BMD, respectively) are characterized by fat replacement of different skeletal muscles in a specific temporal order. Given the structural role of dystrophin in skeletal muscle mechanics, muscle architecture could be important in the progressive pathophysiology of muscle degeneration. Therefore, the aim of this study was to assess the role of muscle architecture in the progression of fat replacement in DMD and BMD. Methods: We assessed the association between literature‐based leg muscle architectural characteristics and muscle fat fraction from 22 DMD and 24 BMD patients. Dixon‐based magnetic resonance imaging estimates of fat fractions at baseline and 12 (only DMD) and 24 months were related to fiber length and physiological cross‐sectional area (PCSA) using age‐controlled linear mixed modeling. Results: DMD and BMD muscles with long fibers and BMD muscles with large PCSAs were associated with increased fat fraction. The effect of fiber length was stronger in muscles with larger PCSA. Discussion: Muscle architecture may explain the pathophysiology of muscle degeneration in dystrophinopathies, in which proximal muscles with a larger mass (fiber length × PCSA) are more susceptible, confirming the clinical observation of a temporal proximal‐to‐distal progression. These results give more insight into the mechanical role in the pathophysiology of muscular dystrophies. Ultimately, this new information can be used to help support the selection of current and the development of future therapies. [ABSTRACT FROM AUTHOR]

Background: Late‐onset Pompe disease (LOPD) is a genetic disorder characterized by progressive degeneration of the skeletal muscles produced by a deficiency of the enzyme acid alpha‐glucosidase. Enzymatic replacement therapy with recombinant human alpha‐glucosidase seems to reduce the progression of the disease; although at the moment, it is not completely clear to what extent. Quantitative muscle magnetic resonance imaging (qMRI) is a good biomarker for the follow‐up of fat replacement in neuromuscular disorders. The aim of this study was to describe the changes observed in fat replacement in skeletal muscles using qMRI in a cohort of LOPD patients followed prospectively. Methods: A total of 36 LOPD patients were seen once every year for 4 years. qMRI, several muscle function tests, spirometry, activities of daily living scales, and quality‐of‐life scales were performed on each visit. Muscle MRI consisted of two‐point Dixon studies of the trunk and thigh muscles. Computer analysis of the images provided the percentage of muscle degenerated and replaced by fat in every muscle (known as fat fraction). Longitudinal analysis of the measures was performed using linear mixed models applying the Greenhouse–Geisser test. Results: We detected a statistically significant and continuous increase in mean thigh fat fraction both in treated (+5.8% in 3 years) and in pre‐symptomatic patients (+2.6% in 3years) (Greenhouse–Geisser p < 0.05). As an average, fat fraction increased by 1.9% per year in treated patients, compared with 0.8% in pre‐symptomatic patients. Fat fraction significantly increased in every muscle of the thighs. We observed a significant correlation between changes observed in fat fraction in qMRI and changes observed in the results of the muscle function tests performed. Moreover, we identified that muscle performance and mean thigh fat fraction at baseline visit were independent parameters influencing fat fraction progression over 4 years (analysis of covariance, p < 0.05). Conclusions: Our study identifies that skeletal muscle fat fraction continues to increase in patients with LOPD despite the treatment with enzymatic replacement therapy. These results suggest that the process of muscle degeneration is not stopped by the treatment and could impact muscle function over the years. Hereby, we show that fat fraction along with muscle function tests can be considered a good outcome measures for clinical trials in LOPD patients. [ABSTRACT FROM AUTHOR]

ABSTRACT: Rotator cuff (RC) muscles undergo several detrimental changes following mechanical unloading resulting from RC tendon tear. In this review, we highlight the pathological causes and consequences of mechanical alterations at the whole muscle, muscle fiber, and muscle resident cell level as they relate to RC disease progression. In brief, the altered mechanical loads associated with RC tear lead to architectural, structural, and compositional changes at the whole‐muscle and muscle fiber level. At the cellular level, these changes equate to direct disruption of mechanobiological signaling, which is exacerbated by mechanically regulated biophysical and biochemical changes to the cellular and extra‐cellular environment (also known as the stem cell “niche”). Together, these data have important implications for both pre‐clinical models and clinical practice. In pre‐clinical models, it is important to recapitulate both the atrophic and degenerative muscle loss found in humans using clinically relevant modes of injury. Clinically, understanding the mechanics and underlying biology of the muscle will impact both surgical decision‐making and rehabilitation protocols, as interventions that may be good for atrophic muscle will have a detrimental effect on degenerating muscle, and vice versa. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:546–556, 2018. [ABSTRACT FROM AUTHOR]

Introduction: In this preliminary study we determined whether MRI markers of cervical muscle degeneration [elevated muscle fatty infiltration (MFI), cross-sectional area (CSA), and reduced relative muscle CSA (rmCSA)] could be modified with exercise in patients with chronic whiplash.Methods: Five women with chronic whiplash undertook 10 weeks of neck exercise. MRI measures of the cervical multifidus (posterior) and longus capitus/colli (anterior) muscles, neck muscle strength, and self-reported neck disability were recorded at baseline and at completion of the exercise program.Results: Overall significant increases in CSA and rmCSA were observed for both muscles, but significant reductions in MFI were only evident in the cervical multifidus muscle. These changes coincided with increased muscle strength and reduced neck disability.Conclusions: MRI markers of muscle morphology in individuals with chronic whiplash appear to be modifiable with exercise. [ABSTRACT FROM AUTHOR]

Duchenne muscular dystrophy (DMD) is a genetic disease that occurs due to the deficiency of the dystrophin protein. Although dystrophin is deficient in all muscles, it is unclear why degeneration progresses differently across muscles in DMD. We hypothesized that each muscle undergoes a different degree of eccentric contraction during gait, which could contribute to the selective degeneration in lower limb muscle, as indicated by various amounts of fatty infiltration. By comparing eccentric contractions quantified from a previous multibody dynamic musculoskeletal gait simulation and fat fractions quantified in a recent imaging study, our preliminary analyses show a strong correlation between eccentric contractions during gait and lower limb muscle fat fractions, supporting our hypothesis. This knowledge is critical for developing safe exercise regimens for the DMD population. This study also provides supportive evidence for using multiscale modeling and simulation of the musculoskeletal system in future DMD research. [ABSTRACT FROM AUTHOR]

Background No standardised method has been adopted for measuring toe-grip strength (TGS), and no reference values have been established for evaluating it. The present study investigated agerelated changes in TGS and the association of TGS with various descriptive characteristics. Methods TGS was measured in both feet of 1842 community-dwelling individuals aged 20-79 years using a toe-grip dynamometer. The participants were classified by decade into six age groups: 20-29, 30-39, 40-49, 50-59, 60-69, and 70-79 years. Correlations for TGS between the dominant and non-dominant sides were analysed according to decade and sex using Pearson's correlation coefficient. The mean TGS and TGS-to-weight ratio (TGS/Wt%) were compared between sexes by each decade and among all decades by sex using two-way analysis of variance with post-hoc tests. To assess relationships between mean TGS and various descriptive characteristics, we determined Pearson's correlation coefficient by sex and performed a stepwise multiple-regression analysis. Significance was set at 5%. Results Correlations for TGS between the dominant and non-dominant sides were significant in all decades by sex, ranging from 0.73 for men in their 70s to 0.91 for women in their 50s. Mean TGS and TGS/Wt% significantly differed between the sexes in all decades and in all decades except the 40s, respectively. In men, the mean TGS and TGS/Wt% significantly decreased with aging after the 50s and 60s, respectively. In women, both the mean TGS and TGS/Wt% significantly decreased between the 40s and 50s and between the 60s and 70s. TGS significantly correlated with age, height, and weight in both sexes. The stepwise multipleregression analysis revealed TGS was significantly associated with sex, age, height, and weight (adjusted R² = 0.31). Conclusions TGS was closely correlated between the dominant and non-dominant sides. TGS and TGS/Wt were significantly reduced with aging after the 50s in men and significantly reduced between the 40s and 50s and between the 60s and 70s in women. Age, sex, height, and weight accounted for only 30.8% of the variance in TGS. Therefore, other factors (e.g. toe flexibility, structural characteristics) should be considered for improving the accuracy of predicting TGS. [ABSTRACT FROM AUTHOR]

Abstract: Muscle atrophy is a known consequence of muscle disuse, muscle denervation and tendon tear. Whereas after nerve injury muscle atrophies in the denervated area, the distribution of muscle atrophy following tear of its tendon is not known. Standardized MRI scans of 64 consecutive, painful shoulders were evaluated for supraspinatus tendon tearing, myotendinous retraction, supraspinatus muscle atrophy, fatty infiltration, ratio of the scapular (deep) and fascial (superficial) muscle area (“symmetry”) and position of the central tendon within the supraspinatus fossa. There were thirteen shoulders with no and eleven shoulders with partial thickness supraspinatus tendon tears. In the forty cases with full thickness tendon tear, there was significant muscle atrophy and fatty infiltration. Atrophy of the fascial muscle portion was 43%, on the bony side it was 9% (p &#60;0.005). The position of the central tendon within the supraspinatus fossa, was unaltered. Muscular changes following tendon tear occur highly asymmetrically: The muscle portion originating from the fascia primarily atrophies, the portion originating from the scapula primarily undergoes fatty infiltration. Muscular changes are not simply a consequence of muscle disuse, but dependent on architectural changes in the muscle. [Copyright &y& Elsevier]

During metamorphosis of the hawkmoth, Manduca sexta, some larval muscles degenerate while others are respecified for new functions. In larvae, accessory planta retractor muscles (APRMs) are present in abdominal segments 1 to 6 (A1 to A6). APRMs serve as proleg retractors in A3 to A6 and body wall muscles in A1 and A2. At pupation, all APRMs degenerate except those in A2 and A3, which are respecified to circulate hemolymph in pupae. The motoneurons that innervate APRMs, the APRs, likewise undergo segment-specific programmed cell death (PCD), as a direct, cell-autonomous response to the prepupal peak of ecdysteroids. The segment-specific patterns of APR and APRM death differ. The present study tested the hypothesis that APRM death is a direct, cell-autonomous response to the prepupal peak of ecdysteroids. Prevention of the prepupal peak prevented APRM degeneration, and replacement of the peak by infusion of 20-hydroxyecdysone restored the correct segment-specific pattern of APRM degeneration. Surgical denervation of APRMs did not perturb their segment-specific degeneration at pupation, indicating that signals from APRs are not required for the muscles' segment-specific responses to ecdysteroids. The possibility that instructive signals originate from APRMs' epidermal attachment points was tested by treating the epidermis with a juvenile hormone analog to prevent pupal development. This manipulation likewise did not alter APRM fate. We conclude that both the muscles and motoneurons in this motor system respond directly and cell-autonomously to prepupal ecdysteroids to produce a segment-specific pattern of PCD that is matched to the functional requirements of the pupal body. © 2004 Wiley Periodicals, Inc. J Neurobiol, 2005 [ABSTRACT FROM AUTHOR]

Following tendon tear, the musculo-tendinous unit retracts permanently, looses muscle fibre volume and is infiltrated with fat. This is currently considered to be an unexplained degenerative process. In a sheep model of chronic tendon tear with delayed tendon repair (35 weeks after tendon release), we studied the nature of these muscle changes in eight experimental animals. At sacrifice (75 weeks after tendon release) the muscle had retracted by 1.7 ± 0.5 cm (9% of entire length, P<0.0001), the pennation angle had increased from 22 ± 2.5° to 50 ± 11° (P<0.0001) and the mean muscle fibre length had shortened from 32 ± 3 to 16 ± 5 mm (50%, P<0.0001). In electron and light microscopy, we found essentially normal muscle fibres with an unaltered fibre diameter and myofibrillar structure, while interstitial fat and fibrous tissue had increased from 3.9% to 45.9% (P<0.0001) of the muscle volume.Geometric modelling showed that the increase of the pennation angle separates the muscle fibre bundles mechanically like limbs of a parallelogram. Infiltrating fat cells fill the created space between the reoriented muscle fibres which may be quantitatively calculated without affecting the structural properties of the muscle cells. Fatty infiltration is therefore not seen as a degenerative process but a necessary rearrangement of the tissue after macroarchitectural changes caused by musculo-tendinous retraction. [Copyright &y& Elsevier]

The masseter and temporalis muscles were studied ultrastructurally in eight cases suffering from restricted mouth opening and TMJ ankylosis. The changes varied from slight degeneration of muscle fibers, such as accumulation of lipid or lipofuscin deposits, Z-band streaming and derangement of myofilaments, in one case to moderate or severe changes of muscle atrophy and necrosis in the remaining seven cases. Nemaline bodies were also observed in one of these seven cases. In addition to these muscle changes neural degeneration especially of myelinated nerves were found in three of the cases studied. The present findings showed that in spite of the diversity of the underlying factors affecting the joint, there was many similarities in the changes observed within the muscle. It is postulated that these degenerative muscle changes probably play an important role in restricted mouth opening and TMJ ankylosis, and that some of these muscle pathology may be the result of neural involvement. [ABSTRACT FROM AUTHOR]