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Endokrynologia Polska 2022Thyrotoxic myopathy is hyperthyroidism accompanied by muscle lesions. It is recognized as the general term for a group of symptoms with several main manifestations of... (Review)
Review
Thyrotoxic myopathy is hyperthyroidism accompanied by muscle lesions. It is recognized as the general term for a group of symptoms with several main manifestations of several hyperthyroidism patients in the course (e.g. muscle weakness, muscle paralysis, or pain). From the clinical perspective, it may only be manifested as muscle-related symptoms. The symptoms of high metabolic syndrome (e.g. thyrotoxicosis) are absent, obscured, or relatively delayed, so it can be easily misdiagnosed. Accordingly, patients experiencing the first symptom of myopathy should concentrate on the possibility of thyrotoxic myopathy. Given the clinical characteristics, thyrotoxic myopathy can be devided into chronic thyrotoxic myopathy, thyrotoxicosis with periodic paralysis, acute thyrotoxic myopathy, hyperthyroidism with myasthenia gravis, as well as infiltrating exophthalmos with ophthalmoplegia. In this paper, we review thyrotoxic myopathy research status, diagnoses, and treatments.
Topics: Humans; Hyperthyroidism; Muscle Weakness; Muscular Diseases; Paralysis; Thyrotoxicosis
PubMed: 35119093
DOI: 10.5603/EP.a2022.0004 -
International Journal of Molecular... Feb 2021We are pleased to announce a Special Issue on the Genetic Basis and Epidemiology of Myopathies. This Special Issue is collecting papers pertaining to various lines of...
We are pleased to announce a Special Issue on the Genetic Basis and Epidemiology of Myopathies. This Special Issue is collecting papers pertaining to various lines of research focusing on the genetic basis and the epidemiology of myopathies. The Guest Editors' note combines the contributing authors' reviews and findings of relevant research, and we hope that future studies on myopathies will attempt to confirm these findings and, additionally, evaluate supplementary phenotypic and histological expressions of myopathies, as well as genetic factors in their pathogenesis.
Topics: Animals; Disease Models, Animal; Genetic Association Studies; Humans; Muscular Diseases; Mutation; Transcription Factors; Tropomyosin
PubMed: 33671495
DOI: 10.3390/ijms22042152 -
Journal of Cachexia, Sarcopenia and... Dec 2023Decreased ryanodine receptor type 1 (RyR1) protein levels are a well-described feature of recessive RYR1-related myopathies. The aim of the present study was twofold:...
BACKGROUND
Decreased ryanodine receptor type 1 (RyR1) protein levels are a well-described feature of recessive RYR1-related myopathies. The aim of the present study was twofold: (1) to determine whether RyR1 content is also decreased in other myopathies and (2) to investigate the mechanisms by which decreased RyR1 protein triggers muscular disorders.
METHODS
We used publicly available datasets, muscles from human inflammatory and mitochondrial myopathies, an inducible muscle-specific RYR1 recessive mouse model and RyR1 knockdown in C2C12 muscle cells to measure RyR1 content and endoplasmic reticulum (ER) stress markers. Proteomics, lipidomics, molecular biology and transmission electron microscopy approaches were used to decipher the alterations associated with the reduction of RyR1 protein levels.
RESULTS
RYR1 transcripts were reduced in muscle samples of patients suffering from necrotizing myopathy (P = 0.026), inclusion body myopathy (P = 0.003), polymyositis (P < 0.001) and juvenile dermatomyositis (P < 0.001) and in muscle samples of myotonic dystrophy type 2 (P < 0.001), presymptomatic (P < 0.001) and symptomatic (P < 0.001) Duchenne muscular dystrophy, Becker muscular dystrophy (P = 0.004) and limb-girdle muscular dystrophy type 2A (P = 0.004). RyR1 protein content was also significantly decreased in inflammatory myopathy (-75%, P < 0.001) and mitochondrial myopathy (-71%, P < 0.001) muscles. Proteomics data showed that depletion of RyR1 protein in C2C12 myoblasts leads to myotubes recapitulating the common molecular alterations observed in myopathies. Mechanistically, RyR1 protein depletion reduces ER-mitochondria contact length (-26%, P < 0.001), Ca transfer to mitochondria (-48%, P = 0.002) and the mitophagy gene Parkinson protein 2 transcripts (P = 0.037) and induces mitochondrial accumulation (+99%, P = 0.005) and dysfunction (P < 0.001). This was associated to the accumulation of deleterious sphingolipid species. Our data showed increased levels of the ER stress marker chaperone-binding protein/glucose regulated protein 78, GRP78-Bip, in RyR1 knockdown myotubes (+45%, P = 0.046), in mouse RyR1 recessive muscles (+58%, P = 0.001) and in human inflammatory (+96%, P = 0.006) and mitochondrial (+64%, P = 0.049) myopathy muscles. This was accompanied by increased protein levels of the pro-apoptotic protein CCAAT-enhancer-binding protein homologous protein, CHOP-DDIT3, in RyR1 knockdown myotubes (+27%, P < 0.001), mouse RyR1 recessive muscles (+63%, P = 0.009), human inflammatory (+50%, P = 0.038) and mitochondrial (+51%, P = 0.035) myopathy muscles. In publicly available datasets, the decrease in RYR1 content in myopathies was also associated to increased ER stress markers and RYR1 transcript levels are inversely correlated with ER stress markers in the control population.
CONCLUSIONS
Decreased RyR1 is commonly observed in myopathies and associated to ER stress in vitro, in mouse muscle and in human myopathy muscles, suggesting a potent role of RyR1 depletion-induced ER stress in the pathogenesis of myopathies.
Topics: Animals; Humans; Mice; Endoplasmic Reticulum Stress; Muscle Fibers, Skeletal; Muscle, Skeletal; Muscular Diseases; Ryanodine Receptor Calcium Release Channel
PubMed: 37964752
DOI: 10.1002/jcsm.13349 -
Annals of Clinical and Translational... May 2023Valosin-containing protein (VCP)-associated multisystem proteinopathy (MSP) is a rare genetic disorder with abnormalities in the autophagy pathway leading to various... (Review)
Review
Valosin-containing protein (VCP)-associated multisystem proteinopathy (MSP) is a rare genetic disorder with abnormalities in the autophagy pathway leading to various combinations of myopathy, bone diseases, and neurodegeneration. Ninety percent of patients with VCP-associated MSP have myopathy, but there is no consensus-based guideline. The goal of this working group was to develop a best practice set of provisional recommendations for VCP myopathy which can be easily implemented across the globe. As an initiative by Cure VCP Disease Inc., a patient advocacy organization, an online survey was initially conducted to identify the practice gaps in VCP myopathy. All prior published literature on VCP myopathy was reviewed to better understand the different aspects of management of VCP myopathy, and several working group sessions were conducted involving international experts to develop this provisional recommendation. VCP myopathy has a heterogeneous clinical phenotype and should be considered in patients with limb-girdle muscular dystrophy phenotype, or any myopathy with an autosomal dominant pattern of inheritance. Genetic testing is the only definitive way to diagnose VCP myopathy, and single-variant testing in the case of a known familial VCP variant, or multi-gene panel sequencing in undifferentiated cases can be considered. Muscle biopsy is important in cases of diagnostic uncertainty or lack of a definitive pathogenic genetic variant since rimmed vacuoles (present in ~40% cases) are considered a hallmark of VCP myopathy. Electrodiagnostic studies and magnetic resonance imaging can also help rule out disease mimics. Standardized management of VCP myopathy will optimize patient care and help future research initiatives.
Topics: Humans; Valosin Containing Protein; Muscular Diseases; Muscular Dystrophies, Limb-Girdle; Phenotype; Proteostasis Deficiencies
PubMed: 37026610
DOI: 10.1002/acn3.51760 -
Indian Journal of Pathology &... May 2022Histopathological analysis of muscle biopsy is a prerequisite in the evaluation of neuromuscular disorders, particularly inflammatory myopathies, metabolic myopathies,... (Review)
Review
Histopathological analysis of muscle biopsy is a prerequisite in the evaluation of neuromuscular disorders, particularly inflammatory myopathies, metabolic myopathies, congenital myopathies, muscular dystrophies and differentiating myopathies and neurogenic disorders with overlapping clinically features. It not only provides useful information that helps in the diagnosis but also treatment and management. Fundamental skills and basic knowledge regarding handling, processing and analyzing a muscle biopsy are required in any specialized or a general pathology lab supporting neuromuscular clinical services. Care during transport of the muscle biopsy, sample receipt in the laboratory and grossing is very important. Standard operating procedure should be followed for the preanalytical steps (freezing and cryomicrotomy), routine and special staining (enzyme and non enzymatic) and immunohistochemistry. A well organized neuromuscular laboratory with good quality management system is necessary for the practice of myopathology. This article gives an overview of establishing such a laboratory.
Topics: Biopsy; Humans; Muscle, Skeletal; Muscular Diseases; Myositis; Neuromuscular Diseases
PubMed: 35562155
DOI: 10.4103/ijpm.ijpm_7_22 -
Clinical Neurophysiology : Official... Feb 2022
Topics: COVID-19; Humans; Muscular Diseases; SARS-CoV-2
PubMed: 34930658
DOI: 10.1016/j.clinph.2021.11.006 -
Clinical Pharmacology and Therapeutics Oct 2014Statins are widely used lipid-lowering drugs that are effective in reducing cardiovascular disease risk. Although they are generally well tolerated, they can cause...
Statins are widely used lipid-lowering drugs that are effective in reducing cardiovascular disease risk. Although they are generally well tolerated, they can cause muscle toxicity, which can lead to severe rhabdomyolysis. Research in this area has been hampered to some extent by the lack of standardized nomenclature and phenotypic definitions. We have used numerical and descriptive classifications and developed an algorithm to define statin-related myotoxicity phenotypes, including myalgia, myopathy, rhabdomyolysis, and necrotizing autoimmune myopathy.
Topics: Autoimmune Diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Muscular Diseases; Myalgia; Myositis; Phenotype; Rhabdomyolysis; Risk Factors; Terminology as Topic; Time Factors
PubMed: 24897241
DOI: 10.1038/clpt.2014.121 -
Reumatologia Clinica 2017Calf pseudohypertrophy due to radiculopathy is an exceptional phenomenon rarely described. We report a 67 year old woman with a previous history of lumbar disc surgery...
Calf pseudohypertrophy due to radiculopathy is an exceptional phenomenon rarely described. We report a 67 year old woman with a previous history of lumbar disc surgery consulting by progressive increase for more than a year of evolution painless right calf associated loss of strength. Electromyographic findings showed chronic S1 radiculopathy and radiologically was appreciated in the medial gastrocnemius and soleus rights substitution of normal muscle tissue by adipose tissue without evidence of myopathy or sarcomatous degeneration.
Topics: Aged; Female; Humans; Hypertrophy; Leg; Magnetic Resonance Imaging; Muscle, Skeletal; Muscular Diseases; Radiculopathy
PubMed: 27101742
DOI: 10.1016/j.reuma.2016.02.012 -
Indian Journal of Pathology &... May 2022Metabolic myopathies are a diverse group of genetic disorders that result in impaired energy production. They are individually rare and several have received the 'orphan... (Review)
Review
Metabolic myopathies are a diverse group of genetic disorders that result in impaired energy production. They are individually rare and several have received the 'orphan disorder' status. However, collectively they constitute a relatively common group of disorders that affect not only the skeletal muscle but also the heart, liver, and brain among others. Mitochondrial disorders, with a frequency of 1/8000 population, are the commonest cause of metabolic myopathies. Three main groups that cause metabolic myopathy are glycogen storage disorders (GSD), fatty acid oxidation defects (FAOD), and mitochondrial myopathies. Clinically, patients present with varied ages at onset and neuromuscular features. While newborns and infants typically present with hypotonia and multisystem involvement chiefly affecting the liver, heart, kidney, and brain, patients with onset later in life present with exercise intolerance with or without progressive muscle weakness and myoglobinuria. In general, GSDs result in high-intensity exercise intolerance while, FAODs, and mitochondrial myopathies predominantly manifest during endurance-type activity, fasting, or metabolically stressful conditions. Evaluation of these patients comprises a meticulous clinical examination and a battery of investigations which includes- exercise stress testing, metabolic and biochemical screening, electrophysiological studies, neuro-imaging, muscle biopsy, and molecular genetics. Accurate and early detection of metabolic myopathies allows timely counseling to prevent metabolic crises and helps in therapeutic interventions. This review summarizes the clinical features, diagnostic tests, pathological features, treatment and presents an algorithm to diagnose these three main groups of disorders.
Topics: Algorithms; Heart; Humans; Infant, Newborn; Metabolism, Inborn Errors; Mitochondrial Myopathies; Muscular Diseases
PubMed: 35562160
DOI: 10.4103/ijpm.ijpm_1088_21 -
Genes Apr 2023Metabolic myopathies are rare inherited disorders that deserve more attention from neurologists and pediatricians. Pompe disease and McArdle disease represent some of... (Review)
Review
Metabolic myopathies are rare inherited disorders that deserve more attention from neurologists and pediatricians. Pompe disease and McArdle disease represent some of the most common diseases in clinical practice; however, other less common diseases are now better-known. In general the pathophysiology of metabolic myopathies needs to be better understood. Thanks to the advent of next-generation sequencing (NGS), genetic testing has replaced more invasive investigations and sophisticated enzymatic assays to reach a final diagnosis in many cases. The current diagnostic algorithms for metabolic myopathies have integrated this paradigm shift and restrict invasive investigations for complicated cases. Moreover, NGS contributes to the discovery of novel genes and proteins, providing new insights into muscle metabolism and pathophysiology. More importantly, a growing number of these conditions are amenable to therapeutic approaches such as diets of different kinds, exercise training protocols, and enzyme replacement therapy or gene therapy. Prevention and management-notably of rhabdomyolysis-are key to avoiding serious and potentially life-threatening complications and improving patients' quality of life. Although not devoid of limitations, the newborn screening programs that are currently mushrooming across the globe show that early intervention in metabolic myopathies is a key factor for better therapeutic efficacy and long-term prognosis. As a whole NGS has largely increased the diagnostic yield of metabolic myopathies, but more invasive but classical investigations are still critical when the genetic diagnosis is unclear or when it comes to optimizing the follow-up and care of these muscular disorders.
Topics: Infant, Newborn; Humans; Quality of Life; Muscular Diseases; Metabolism, Inborn Errors; Glycogen Storage Disease Type V; High-Throughput Nucleotide Sequencing
PubMed: 37239314
DOI: 10.3390/genes14050954