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Joint Bone Spine Jan 2020Statin-associated muscle symptoms (SAMSs) vary considerably in frequency and severity, with a spectrum extending from myalgia with normal creatine kinase (CK) levels or...
Statin-associated muscle symptoms (SAMSs) vary considerably in frequency and severity, with a spectrum extending from myalgia with normal creatine kinase (CK) levels or asymptomatic hyperCKemia to potentially life-threatening rhabdomyolysis and necrotizing autoimmune myopathy. Myalgia with CK elevation is the most common presentation. Onset is usually within 1 month after statin initiation or dosage intensification, and the symptoms can be expected to resolve within a few weeks after treatment discontinuation. The mechanism of muscle injury combines statin accumulation within muscles, which varies with the type and dosage of the drug; muscle fragility; abnormalities in statin transport or liver metabolism; drug-drug interactions; and genetic susceptibility. HMG-CoA reductase inhibition in muscles by statins exerts pleiotropic effects that can affect energy metabolism, induce mitochondrial dysfunction, modify lipid oxidation, promote apoptosis and cell membrane lysis, alter muscle protein synthesis, or trigger an autoimmune process. Statins are used to treat several chronic conditions and comorbidities, including inflammatory rheumatic diseases, which are associated with an increased cardiovascular risk. When the cardiovascular risk is high or very high, statin therapy is indispensable and has a very favorable risk/benefit ratio. Otherwise, the risks should be weighed against the benefits before reinitiating statin therapy, and a different statin or lower dosage should be used. If statin therapy cannot be successfully reintroduced, other classes of lipid-lowering drugs should be considered. Severe SAMSs with major weakness and marked CK elevation should suggest the rare eventuality of necrotizing autoimmune myopathy and prompt an anti-HMGCR antibody assay and muscle biopsy to ensure that immunosuppressant therapy is started rapidly if needed.
Topics: Autoimmune Diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Muscular Diseases; Myalgia; Rhabdomyolysis
PubMed: 30735805
DOI: 10.1016/j.jbspin.2019.01.018 -
Radiologic Clinics of North America Sep 2017This article clarifies the current role of MR imaging in the assessment of myopathies. Typical MR imaging findings are discussed for different forms of myopathies,... (Review)
Review
This article clarifies the current role of MR imaging in the assessment of myopathies. Typical MR imaging findings are discussed for different forms of myopathies, including idiopathic inflammatory myopathies, muscular dystrophies, and congenital myopathies. The last section deals with advanced MR imaging techniques and their potential role in further characterization of muscular disease.
Topics: Humans; Magnetic Resonance Imaging; Muscle, Skeletal; Muscular Diseases
PubMed: 28774448
DOI: 10.1016/j.rcl.2017.04.010 -
Neuropathology : Official Journal of... Apr 2020Here, we report about reducing body myopathy, associated with a mutation in the four and a half LIM domain 1 gene (FHL1), identified in a 40-year-old woman who was...
Here, we report about reducing body myopathy, associated with a mutation in the four and a half LIM domain 1 gene (FHL1), identified in a 40-year-old woman who was suffering from subtle muscle weakness since the age of six and a limping gait since the age of 22 years. In addition to her elevated muscle enzyme level and magnetic resonance imaging, myopathy was highly suspected considering progression of symptoms. Nerve conduction studies and electromyogram suggested myopathy. The muscle biopsy revealed severe dystrophic features with many reducing bodies on hematoxylin and eosin, nicotinomide adenine dinucleotide dehydrogenase-tetrazolium reductase (NADH-TR), and modified Gomori stains and ubiquitin immunohistochemistry. Whole-exome sequencing revealed Xq26.3 encoding FHL1 missense mutations (NM_001159704) in exon 4: p.C150R, c.T448C. FHL1-mutated "reducing body myopathy" is worth reporting based on its rarity and unique clinicopathologic features including ultrastructure. The confirmative diagnosis is still very difficult before gene analysis because clinical and pathological features of this disease overlap with other myofibrillar myopathies. We stress the importance of genotype-phenotype correlation to obtain a precise diagnosis.
Topics: Adult; Female; Genetic Diseases, X-Linked; Humans; Intracellular Signaling Peptides and Proteins; LIM Domain Proteins; Muscle Proteins; Muscular Diseases; Mutation, Missense
PubMed: 31803991
DOI: 10.1111/neup.12619 -
Continuum (Minneapolis, Minn.) Dec 2016This article discusses the clinical features, pathophysiology, and management of toxic and endocrine myopathies. (Review)
Review
PURPOSE OF REVIEW
This article discusses the clinical features, pathophysiology, and management of toxic and endocrine myopathies.
RECENT FINDINGS
Early detection and expeditious correction of metabolic disturbances in endocrinopathies such as Cushing syndrome, thyroid and parathyroid diseases, and acromegaly can minimize and prevent neurologic complications including myopathy. Recently proposed mechanisms of injury in patients with critical illness myopathy include inhibition of protein synthesis, mitochondrial dysfunction, disruption of the ubiquitin-proteasome system, oxidative stress, and disruption of intramuscular calcium homeostasis, which can cause a myosin-loss myopathy. Mechanisms underlying toxic myopathies include myosin loss; damage to cellular structures, including myofibrils and organelles such as lysosomes and mitochondria; inflammation; and necrosis. Presentations range anywhere from acute, painful, and necrotic myopathies, as can occur in statin myopathy, to more insidious presentations such as steroid myopathy.
SUMMARY
Endocrinopathies known to cause myopathy include thyroid and parathyroid diseases, disorders of the adrenal axis such as Cushing syndrome, and acromegaly. Patients in the intensive care unit are at risk for developing critical illness myopathy, also known as myosin-loss myopathy, which should be considered if intensive care unit acquired weakness develops. The most common toxic agents associated with myopathy include statins and other lipid-lowering medications, corticosteroids, colchicine, amiodarone, hydroxychloroquine, and chloroquine.
Topics: Adrenal Cortex Hormones; Adult; Endocrine System Diseases; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypothyroidism; Intensive Care Units; Male; Middle Aged; Muscular Diseases; Polyneuropathies
PubMed: 27922495
DOI: 10.1212/CON.0000000000000407 -
Radiographics : a Review Publication of... 2018Atraumatic disorders of skeletal muscles include congenital variants; inherited myopathies; acquired inflammatory, infectious, or ischemic disorders; neoplastic... (Review)
Review
Atraumatic disorders of skeletal muscles include congenital variants; inherited myopathies; acquired inflammatory, infectious, or ischemic disorders; neoplastic diseases; and conditions leading to muscle atrophy. These have overlapping appearances at magnetic resonance (MR) imaging and are challenging for the radiologist to differentiate. The authors organize muscle disorders into four MR imaging patterns: (a) abnormal anatomy with normal signal intensity, (b) edema/inflammation, (c) mass, and (d) atrophy, highlighting each of their key clinical and imaging findings. Anatomic muscle variants, while common, do not produce signal intensity alterations and therefore are easily overlooked. Muscle edema is the most common pattern but is nonspecific, with a broad differential diagnosis. Autoimmune, paraneoplastic, and drug-induced myositis tend to be symmetric, whereas infection, radiation-induced injury, and myonecrosis are focal asymmetric processes. Architectural distortion in the setting of muscle edema suggests one of these latter processes. Intramuscular masses include primary neoplasms, metastases, and several benign masslike lesions that simulate malignancy. Some lesions, such as lipomas, low-flow vascular malformations, fibromatoses, and subacute hematomas, are distinctive, but many intramuscular masses ultimately require a biopsy for definitive diagnosis. Atrophy is the irreversible end result of any muscle disease of sufficient severity and is the dominant finding in disorders such as the muscular dystrophies, denervation myopathy, and sarcopenia. This imaging-based classification, in correlation with clinical and laboratory data, will aid the radiologist in interpreting MR imaging findings in patients with atraumatic muscle disorders. RSNA, 2018.
Topics: Diagnosis, Differential; Humans; Magnetic Resonance Imaging; Muscle, Skeletal; Muscular Diseases
PubMed: 29451848
DOI: 10.1148/rg.2017170112 -
Cell Calcium Mar 2021Mitochondrial activity warrants energy supply to oxidative myofibres to sustain endurance workload. The maintenance of mitochondrial homeostasis is ensured by the... (Review)
Review
Mitochondrial activity warrants energy supply to oxidative myofibres to sustain endurance workload. The maintenance of mitochondrial homeostasis is ensured by the control of fission and fusion processes and by the mitophagic removal of aberrant organelles. Many diseases are due to or characterized by dysfunctional mitochondria, and altered mitochondrial dynamics or turnover trigger myopathy per se. In this review, we will tackle the role of mitochondrial dynamics, turnover and metabolism in skeletal muscle, both in health and disease.
Topics: Animals; Health; Humans; Mitochondria, Muscle; Mitochondrial Dynamics; Mitophagy; Muscle, Skeletal; Muscular Diseases
PubMed: 33550207
DOI: 10.1016/j.ceca.2021.102357 -
Joint Bone Spine Jan 2024
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Muscular Diseases; Autoantibodies
PubMed: 37634874
DOI: 10.1016/j.jbspin.2023.105630 -
Clinics in Chest Medicine Jun 2018Metabolic myopathies are a heterogeneous group of disorders characterized by inherited defects of enzymatic pathways involved in muscle cellular energetics and adenosine... (Review)
Review
Metabolic myopathies are a heterogeneous group of disorders characterized by inherited defects of enzymatic pathways involved in muscle cellular energetics and adenosine triphosphate synthesis. Skeletal and respiratory muscles are most affected. There are multiple mechanisms of disease. The age of onset and prognosis vary. Metabolic myopathies cause exercise intolerance, myalgia, and increase in muscle breakdown products during exercise. Some affect smooth muscle like the diaphragm and cause respiratory failure. The pathophysiology is complex and the evidence in literature to guide diagnosis and management is sparse. Treatment is limited. This review discusses the pathophysiology and diagnostic evaluation of these disorders.
Topics: Humans; Muscular Diseases; Respiratory Insufficiency
PubMed: 29779598
DOI: 10.1016/j.ccm.2018.02.001 -
Critical Care Clinics Oct 2014Neuromuscular sequelae are common in the critically ill. Critical illness polyneuropathy and critical illness myopathy are neuromuscular complications of sepsis or... (Review)
Review
Neuromuscular sequelae are common in the critically ill. Critical illness polyneuropathy and critical illness myopathy are neuromuscular complications of sepsis or iatrogenic complications of treatments required in intensive care. This article discusses the diagnosis, treatment, and prognosis of these disorders based on a literature review. This review found that glycemic control, early mobilization, and judicious use of steroids and neuromuscular blocking agents are the primary approaches to reduce the incidence and severity of neuromuscular complications in affected patients.
Topics: Critical Care; Critical Illness; Humans; Muscular Diseases; Polyneuropathies; Practice Guidelines as Topic; Prognosis; Sepsis
PubMed: 25257741
DOI: 10.1016/j.ccc.2014.06.008 -
Neurologic Clinics Nov 2020Channelopathies, neuromuscular junction disorders, and myopathies represent multiple mechanisms by which toxins can affect the peripheral nervous system. These toxins... (Review)
Review
Channelopathies, neuromuscular junction disorders, and myopathies represent multiple mechanisms by which toxins can affect the peripheral nervous system. These toxins include ciguatoxin, tetrodotoxin, botulinum toxin, metabolic poisons, venomous snake bites, and several medications. These toxins are important to be aware of because they can lead to serious symptoms, disability, or even death, and many can be treated if recognized ear.
Topics: Channelopathies; Humans; Muscular Diseases; Neuromuscular Junction Diseases; Neurotoxicity Syndromes; Toxins, Biological
PubMed: 33040860
DOI: 10.1016/j.ncl.2020.07.001