Progression Of Muscle Degeneration Research Articles

Degenerative Rotator Cuff Tears: Refining Surgical Indications Based on Natural History Data.

Degenerative rotator cuff tears are the most common cause of shoulder pain and have a strong association with advanced aging. Considerable variation exists in surgeons' perceptions on the recommended treatment of patients with painful rotator cuff tears. Natural history studies have better outlined the risks of tear enlargement, progression of muscle degeneration, and decline in the function over time. This information combined with the known factors potentially influencing the rate of successful tendon healing such as age, tear size, and severity of muscle degenerative changes can be used to better refine appropriate surgical indications. Although conservative treatment can be successful in the management of many of these tears, risks to nonsurgical treatment also exist. The application of natural history data can stratify atraumatic degenerative tears according to the risk of nonsurgical treatment and better identify tears where early surgical intervention should be considered.

DIAGNOSTIC OPPORTUNITIES OF MUSCLE MRI IN NEUROMUSCULAR DISORDERS

Considerable clinical and genetic heterogeneity of neuromuscular disorders poses a significant challenge for their diagnosis. Unfortunately in Russia, morphologists use very limited amount of immunohistochemical techniques in analysis of muscle biopsy, and such method as quantified protein western blotting is not used at all. This situation does not facilitate provisional diagnosis, that later could be confirmed genetically. One of the modern diagnostic methods is muscle MRI. We examined 231 patients with suspicion on neuromuscular disorder using muscle MRI. Muscle MRI with following genetic examination able to establish the correct diagnosis in 125 cases (54.1%). Muscle MRI allowed to diagnose such neuromuscular diseases as Duchenne muscular dystrophy, Bethlem myopathy, Emery-Dreifuss muscular dystrophy, LGMD 2A ( с alpainopathy) and LGMD 2B (dysferinopathy). We revealed the special diagnostic pattern of skeletal muscles degeneration in lower extremities for each of above mentioned diseases. In 57 (24.7%) patients the diagnosis of neuromuscular disease was withdrawn due to complete absence of degenerative changes and in 49 (21.4%) patients we found nonspecific degenerative changes in the muscles that gave us various differential diagnostic algorithms. In conclusion, we consider MRI of thigh and calf muscles as a highly informative tool for patients with neuromuscular disorders that can be used not only for diagnostic purposes, but also for assess of progression of muscle degeneration.

A prospective evaluation of survivorship of asymptomatic degenerative rotator cuff tears.

The purpose of this prospective study was to report the long-term risks of rotator cuff tear enlargement and symptom progression associated with degenerative asymptomatic tears. Subjects with an asymptomatic rotator cuff tear in one shoulder and pain due to rotator cuff disease in the contralateral shoulder enrolled as part of a prospective longitudinal study. Two hundred and twenty-four subjects (118 initial full-thickness tears, fifty-six initial partial-thickness tears, and fifty controls) were followed for a median of 5.1 years. Validated functional shoulder scores were calculated (visual analog pain scale, American Shoulder and Elbow Surgeons [ASES], and simple shoulder test [SST] scores). Subjects were followed annually with shoulder ultrasonography and clinical evaluations. Tear enlargement was seen in 49% of the shoulders, and the median time to enlargement was 2.8 years. The occurrence of tear-enlargement events was influenced by the severity of the final tear type, with enlargement of 61% of the full-thickness tears, 44% of the partial-thickness tears, and 14% of the controls (p < 0.05). Subject age and sex were not related to tear enlargement. One hundred subjects (46%) developed new pain. The final tear type was associated with a greater risk of pain development, with the new pain developing in 28% of the controls, 46% of the shoulders with a partial-thickness tear, and 50% of those with a full-thickness tear (p < 0.05). The presence of tear enlargement was associated with the onset of new pain (p < 0.05). Progressive degenerative changes of the supraspinatus muscle were associated with tear enlargement, with supraspinatus muscle degeneration increasing in 4% of the shoulders with a stable tear compared with 30% of the shoulders with tear enlargement (p < 0.05). Nine percent of the shoulders with a stable tear showed increased infraspinatus muscle degeneration compared with 28% of those in which the tear had enlarged (p = 0.07). This study demonstrates the progressive nature of degenerative rotator cuff disease. The risk of tear enlargement and progression of muscle degeneration is greater for shoulders with a full-thickness tear, and tear enlargement is associated with a greater risk of pain development across all tear types. Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

IGF signaling in muscle degenerative diseases

IGF signaling in muscle degenerative diseases

Troponin T is essential for sarcomere assembly in zebrafish skeletal muscle

In striated muscle, the basic contractile unit is the sarcomere, which comprises myosin-rich thick filaments intercalated with thin filaments made of actin, tropomyosin and troponin. Troponin is required to regulate Ca2+-dependent contraction, and mutant forms of troponins are associated with muscle diseases. We have disrupted several genes simultaneously in zebrafish embryos and have followed the progression of muscle degeneration in the absence of troponin. Complete loss of troponin T activity leads to loss of sarcomere structure, in part owing to the destructive nature of deregulated actin–myosin activity. When troponin T and myosin activity are simultaneously disrupted, immature sarcomeres are rescued. However, tropomyosin fails to localise to sarcomeres, and intercalating thin filaments are missing from electron microscopic cross-sections, indicating that loss of troponin T affects thin filament composition. If troponin activity is only partially disrupted, myofibrils are formed but eventually disintegrate owing to deregulated actin–myosin activity. We conclude that the troponin complex has at least two distinct activities: regulation of actin–myosin activity and, independently, a role in the proper assembly of thin filaments. Our results also indicate that sarcomere assembly can occur in the absence of normal thin filaments.

Troponin T is essential for sarcomere assembly in zebrafish skeletal muscle.

In striated muscle, the basic contractile unit is the sarcomere, which comprises myosin-rich thick filaments intercalated with thin filaments made of actin, tropomyosin and troponin. Troponin is required to regulate Ca(2+)-dependent contraction, and mutant forms of troponins are associated with muscle diseases. We have disrupted several genes simultaneously in zebrafish embryos and have followed the progression of muscle degeneration in the absence of troponin. Complete loss of troponin T activity leads to loss of sarcomere structure, in part owing to the destructive nature of deregulated actin-myosin activity. When troponin T and myosin activity are simultaneously disrupted, immature sarcomeres are rescued. However, tropomyosin fails to localise to sarcomeres, and intercalating thin filaments are missing from electron microscopic cross-sections, indicating that loss of troponin T affects thin filament composition. If troponin activity is only partially disrupted, myofibrils are formed but eventually disintegrate owing to deregulated actin-myosin activity. We conclude that the troponin complex has at least two distinct activities: regulation of actin-myosin activity and, independently, a role in the proper assembly of thin filaments. Our results also indicate that sarcomere assembly can occur in the absence of normal thin filaments.

Fatty Infiltration and Atrophy of the Rotator Cuff do not Improve after Rotator Cuff Repair and Correlate with Poor Functional Outcome

Background The role of degenerative changes in rotator cuff musculature with respect to the functional outcomes of rotator cuff repair have only recently been recognized and are still not well understood. In addition, the reversibility of these changes with repair of the tendons is questionable. Hypothesis Poorer preoperative muscle quality negatively affects outcome, and a successful outcome (in terms of a healed repair) might demonstrate improvements in fatty infiltration and muscle atrophy. Study Design Cohort study; Level of evidence, 2. Methods Thirty-eight patients (mean age, 62 years) were prospectively evaluated with preoperative and 1-year postoperative clinical examination and appropriate magnetic resonance image sequencing to determine grades of muscle atrophy and fatty infiltration of the supraspinatus and infraspinatus muscles. American Shoulder and Elbow Society (ASES), Constant, and pain scores were determined as well as strength measurements. The retear rate and progression of muscle degeneration were also evaluated. Independent predictors of outcome measurements and cuff integrity were determined. Results The overall clinical outcome, including ASES, Constant, and pain scores, improved significantly (P < .0001). Strength in forward elevation improved significantly (P < .006), while external rotation strength did not. There was a strongly negative correlation between muscle quality and outcome results in most cases. When the results were adjusted for multivariate effect, muscle atrophy and fatty infiltration of the infraspinatus muscle were the only independent predictors of ASES and Constant scores (P < .03). Tear size and rotator cuff healing did not play an independent role. Tear size, however, was the only independent predictor of ultimate cuff integrity (P = .002). Both atrophy and fatty infiltration progressed significantly over the course of the study. In cases in which the tendon had re-torn, the progression was found to be more significant than when the repair proved successful (P < .003). Conclusion Muscle atrophy and fatty infiltration of the rotator cuff muscles, particularly of the infraspinatus, play a significant role in determining functional outcome after cuff repair. Tear size appears to have the most influential effect on repair integrity. A successful repair did not lead to improvement or reversal of muscle degeneration and a failed repair resulted in significantly more progression. In general, healed repairs demonstrated minimal progression. These findings suggest that repairs should be performed, if possible, before more significant deterioration in the cuff musculature in order to optimize outcomes, and that understanding the degree of muscle atrophy and fatty infiltration before surgery can help guide patient expectations.