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Postgraduate Medical Journal Aug 2013Proximal myopathy presents as symmetrical weakness of proximal upper and/or lower limbs. There is a broad range of underlying causes including drugs, alcohol, thyroid... (Review)
Review
Proximal myopathy presents as symmetrical weakness of proximal upper and/or lower limbs. There is a broad range of underlying causes including drugs, alcohol, thyroid disease, osteomalacia, idiopathic inflammatory myopathies (IIM), hereditary myopathies, malignancy, infections and sarcoidosis. Clinical assessment should aim to distinguish proximal myopathy from other conditions that can present similarly, identify patients who need prompt attention, like those with cardiac, respiratory or pharyngeal muscle involvement, and determine underlying cause of myopathy. Initial evaluation should include simple tests, like creatine kinase, thyroid function and (25)OH vitamin D levels, but further evaluation including neurophysiological studies, muscle imaging and muscle biopsy should be considered for patients in whom no toxic, metabolic or endocrine cause is found, and in those with clinical features suggestive of inflammatory or hereditary myopathy. Additionally, screening for malignancy and testing for anti-Jo1 antibody is indicated for selected patients with IIM. Management depends on underlying cause, and includes measures, such as removal of offending agent, correction of endocrine or metabolic problem, corticosteroids and immunosuppressive therapy for IIM, and physical therapy, rehabilitation and genetic counselling for muscular dystrophies.
Topics: Creatine Kinase; Diagnosis, Differential; Genetic Predisposition to Disease; Humans; Muscles; Muscular Diseases; Myositis; Vitamin D; Vitamin D Deficiency
PubMed: 23596213
DOI: 10.1136/postgradmedj-2013-131752 -
Autoimmunity Reviews Feb 2022This review is focused on the myopathological spectrum of immune mediated necrotizing myopathies (IMNMs) and its differentiation with other, potentially mimicking,... (Review)
Review
This review is focused on the myopathological spectrum of immune mediated necrotizing myopathies (IMNMs) and its differentiation with other, potentially mimicking, inflammatory and non-inflammatory myopathies. IMNMs are a subgroup of idiopathic inflammatory myopathies (IIMs) characterized by severe clinical presentation with rapidly progressive muscular weakness and creatine kinase elevation, often requiring early aggressive immunotherapy, associated to the presence of muscle specific autoantibodies (MSA) against signal recognition particle (SRP) or 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). Muscle biopsy usually shows unspecific features consisting in prominent necrosis and regeneration of muscle fibres with mild or absent inflammatory infiltrates, inconstant and faint expression of major histocompatibility complex (MHC) class I and variable deposition of C5b-9 on sarcolemma. Several conditions could present similar histopathological findings leading to possible misdiagnosis of IMNM with other IIMs or non-inflammatory myopathies (nIMs) and viceversa. This review analyses the muscle biopsy data in IMNMs through a systematic revision of the literature from the last five decades. Several histopathological variables have been considered in both SRP- and HMGCR-IMNM, and compared to other IIMs - as dermatomyositis (DM) and anti-synthethase syndrome (ASS) - or other nIMs -as toxic myopathies (TM), critical illness myopathy (CIM) and muscular dystrophy (MD) - to elucidate similarities and differences among these potentially mimicking conditions. The major histopathological findings of IMNMs were: very frequent necrosis and regeneration of muscle fibres (93%), mild inflammatory component mainly constituted by scattered isolated (65%) CD68-prevalent (68%) cells, without CD8 invading/surrounding non-necrotic fibres, variable expression of MHC-I in non-necrotic fibres (56%) and constant expression of sarcoplasmic p62, confirming those that are widely considered the major histological characteristics of IMNMs. Conversely, only 42% of biopsies showed a sarcolemmal deposition of C5b-9 component. Few differences between SRP and HMGCR IMNMs consisted in more severe necrosis and regeneration in SRP than in HMGCR (p = 0.01); more frequent inflammatory infiltrates (p = 0.007) with perivascular localization (p = 0.01) and clustered expression of MHC-I (p = 0.007) in HMGCR; very low expression of sarcolemmal C5b-9 in SRP (18%) compared to HMGCR (56%) (p = 0.0001). Milder necrosis and regeneration, detection of perifascicular pathology, presence of lymphocytic inflammatory infiltrates and myofibre expression of MxA help to distinguish DM or ASS from IMNM. nIMs can present signs of inflammation at muscle biopsy. Low fibre size variability with overexpression of both MHC-I and II, associated with C5b-9 deposition, could could be observed in CIM, while increased connective tissue should lead to consider MD, or TM in absence of C5b-9 deposition. Nevertheless, these features are not constantly detected and muscle biopsy could not be diriment. For this reason, muscle biopsy should always be critically considered in light of the clinical context before concluding for a definite diagnosis of IMNM, only based on histopathological findings. More rigorous collection and analysis of muscle biopsy is warranted to obtain a higher quality and more homogeneous histopathological data in inflammatory myopathies.
Topics: Autoantibodies; Autoimmune Diseases; Humans; Muscle, Skeletal; Muscular Diseases; Myositis; Necrosis
PubMed: 34798316
DOI: 10.1016/j.autrev.2021.102993 -
Journal of Clinical Neuromuscular... Mar 2019We review the development of exon 51 skipping therapy with eteplirsen for Duchenne muscular dystrophy, including the recent report of long-term, sustained dystrophin... (Review)
Review
We review the development of exon 51 skipping therapy with eteplirsen for Duchenne muscular dystrophy, including the recent report of long-term, sustained dystrophin production. Studies of the late-life health profile of patients with Duchenne muscular dystrophy, early detection of left ventricular systolic dysfunction, and caregiver burden are also covered. A study of skeletal muscle magnetic resonance imaging in dysferlinopathies provides an extensive, detailed map of the involved muscles and consistency across phenotypes. Regarding the category of autoimmune myopathies, we discuss an article on the clinical and laboratory features associated with PM/Scl antibodies in comparison with other autoimmune myopathy subgroups. Finally, the overall increase in mortality in inflammatory myopathies is highlighted in a recent report from Sweden.
Topics: Autoantibodies; Humans; Medicine in Literature; Muscle, Skeletal; Muscular Diseases
PubMed: 30801483
DOI: 10.1097/CND.0000000000000226 -
Current Opinion in Neurology Oct 2022The global spread of severe acute respiratory syndrome coronavirus 2 resulted in many cases of acute and postacute muscular symptoms. In this review, we try to decipher... (Review)
Review
PURPOSE OF REVIEW
The global spread of severe acute respiratory syndrome coronavirus 2 resulted in many cases of acute and postacute muscular symptoms. In this review, we try to decipher the potential underlying pathomechanisms and summarize the potential links between viral infection and muscle affection.
RECENT FINDINGS
Disregarding single case studies that do not allow safe conclusions due to the high number of infections, histopathological evidence of myositis has only been reported in deceased individuals with severe COVID-19. Postacute myalgia and weakness seem to occur in a subset of patients up to one year after initial infection, reminiscent of postinfectious syndromes (PIS) described in prior epidemics and pandemics of the past.
SUMMARY
COVID-19 associated myopathy likely comprises different entities with heterogeneous pathomechanisms. Individual factors such as disease severity and duration, age, sex, constitutional susceptibilities, and preexisting conditions are important to consider when formulating a diagnosis. Persisting symptoms show overlapping features with PIS or postintensive care syndrome. In lack of strong evidence for a direct infection of myocytes, inflammatory myopathies associated with COVID-19 are presumably immune-mediated. Differential diagnosis of rheumatological and nonmuscular neurological origin coinciding with the infection need to be considered, due to the extremely high numbers of newly occurring infections the last 2 years.
Topics: COVID-19; Humans; Muscular Diseases; Pandemics; SARS-CoV-2; Virus Diseases
PubMed: 35950722
DOI: 10.1097/WCO.0000000000001101 -
Rinsho Shinkeigaku = Clinical Neurology Mar 2020Inflammatory myopathies are a heterogeneous group of immune-mediated diseases that involve skeletal muscle as well as many other organs. The classification of... (Review)
Review
Inflammatory myopathies are a heterogeneous group of immune-mediated diseases that involve skeletal muscle as well as many other organs. The classification of inflammatory myopathies has been based on clinical diagnoses, pathological diagnoses, and autoantibodies, independently. Antisynthetase syndrome, characterized by myositis, interstitial lung disease, skin rash, arthropathy, and Raynaud phenomenon, is a clinical entity based on the presence of aminoacyl transfer RNA synthetase (ARS) antibodies in patients' serum. A cohort study of muscle biopsy entitled "Integrated Diagnosis Project for Inflammatory Myopathies" revealed that of 460 patients with idiopathic inflammatory myopathies, 51 (11%; female:male, 31:20) had antisynthetase myopathy. It is noted that anti-OJ antibodies, one of anti-ARS antibody subtypes, are clearly detected by RNA immunoprecipitation, but not conventional detection methods including line blot and enzyme-linked immunosorbent assays. The combined mean onset age of the patients was 60 years (range 13-85 years). There were no significant HLA-DRB1 alleles associated with anti-ARS antibodies. All patients with antisynthetase myopathy patients presented muscle limb weakness; 14 had severe weakness, 17 neck weakness, 15 dysphagia, and 15 muscle atrophy. Although patients with anti-OJ antibodies showed severe muscle weakness, the clinical presentations defined by anti-ARS antibodies were relatively homogeneous. In muscle pathology, perifascicular necrosis is a distinctive hallmark of antisynthetase myopathy. Patients with antisynthetase myopathy responded to the combination of immunosuppressive therapy, with favorable outcomes. However, interstitial lung disease, found in 41 patients, was more closely related to mortality than myositis. Antisynthetase myopathy has a distinct clinical and histological entity among idiopathic inflammatory myopathies.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amino Acyl-tRNA Synthetases; Autoantibodies; Exanthema; Female; Humans; Immunoprecipitation; Immunosuppressive Agents; Joint Diseases; Lung Diseases, Interstitial; Male; Middle Aged; Muscle Weakness; Muscles; Muscular Diseases; Syndrome; Young Adult
PubMed: 32101845
DOI: 10.5692/clinicalneurol.cn-001383 -
Clinics in Perinatology Mar 2020The congenital muscular dystrophies and congenital myopathies are a heterogenous group of diseases with a wide variety of presentations and outcomes. With the growing... (Review)
Review
The congenital muscular dystrophies and congenital myopathies are a heterogenous group of diseases with a wide variety of presentations and outcomes. With the growing understanding of genetic involvement, and developing therapies, having a genetically confirmed diagnosis with phenotype correlation is essential. To achieve this, a structured approach is warranted to each child to ensure that mimickers are excluded. By structuring the evaluation appropriately, the clinician can help expedite the evaluation of these infants in a cost-effective manner. Understanding the pitfalls of each step of testing will allow the clinician to better understand variants in presentation and avoid cognitive errors in the process.
Topics: Diagnosis, Differential; Humans; Infant, Newborn; Muscular Diseases; Muscular Dystrophies; Neonatal Screening; Phenotype
PubMed: 32000926
DOI: 10.1016/j.clp.2019.10.005 -
Cleveland Clinic Journal of Medicine Oct 2019Patients with muscle diseases are often seen initially by general practitioners. This article reviews how to evaluate and manage such patients, including those taking a... (Review)
Review
Patients with muscle diseases are often seen initially by general practitioners. This article reviews how to evaluate and manage such patients, including those taking a statin, how to interpret creatine kinase (CK) test results, and how to recognize common as well as potentially dangerous myopathies.
Topics: Adult; Aged; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Internal Medicine; Male; Middle Aged; Muscle Weakness; Muscular Diseases; Symptom Assessment
PubMed: 31597080
DOI: 10.3949/ccjm.86gr.19001 -
Neurophysiologie Clinique = Clinical... Jun 1997Electromyography (EMG) is the most common procedure for screening patients with myopathies and remains the most important technique for assessing the course of the... (Review)
Review
Electromyography (EMG) is the most common procedure for screening patients with myopathies and remains the most important technique for assessing the course of the disease over time. Fibrillation potentials, positive sharp waves, myotonic or complex repetitive discharge, as well as polyphasic potentials are non specific and can occur in both myopathic and neurogenic lesions. The most sensitive and specific parameter for myopathy in conventional EMG is the decreased duration of motor unit potentials (MUP), but this can also be seen in disorders of the terminal motor fibers or the neuromuscular junction. More advanced techniques such as single fiber EMG, macro EMG, scanning EMG and turns/amplitude analysis have opened additional possibilities for analysis of the motor unit and the interference pattern, by which both the sensitivity to early changes and specificity for myopathic alterations is increased. The importance of combining different techniques to improve diagnostic yield and specificity is stressed.
Topics: Electromyography; Evoked Potentials, Motor; Humans; Mass Screening; Motor Neurons; Muscular Diseases
PubMed: 9260160
DOI: 10.1016/s0987-7053(97)83775-6 -
Muscle & Nerve Dec 2019Although myopathies and neuromuscular junction disorders are typically distinct, their coexistence has been reported in several inherited and acquired conditions.... (Review)
Review
Although myopathies and neuromuscular junction disorders are typically distinct, their coexistence has been reported in several inherited and acquired conditions. Affected individuals have variable clinical phenotypes but typically display both a decrement on repetitive nerve stimulation and myopathic findings on muscle biopsy. Inherited causes include myopathies related to mutations in BIN1, DES, DNM2, GMPPB, MTM1, or PLEC and congenital myasthenic syndromes due to mutations in ALG2, ALG14, COL13A1, DOK7, DPAGT1, or GFPT1. Additionally, a decrement due to muscle fiber inexcitability is observed in certain myotonic disorders. The identification of a defect of neuromuscular transmission in an inherited myopathy may assist in establishing a molecular diagnosis and in selecting patients who would benefit from pharmacological correction of this defect. Acquired cases meanwhile stem from the co-occurrence of myasthenia gravis or Lambert-Eaton myasthenic syndrome with an immune-mediated myopathy, which may be due to paraneoplastic disorders or exposure to immune checkpoint inhibitors.
Topics: Cardiomyopathies; Electrodiagnosis; Electromyography; Humans; Muscle, Skeletal; Muscular Diseases; Muscular Dystrophies; Myasthenia Gravis; Myasthenic Syndromes, Congenital; Myopathies, Structural, Congenital; Myotonic Disorders; Neural Conduction; Neuromuscular Junction
PubMed: 31449669
DOI: 10.1002/mus.26676 -
Pharmacological Reports : PR 2011Statins are considered to be safe, well tolerated and the most efficient drugs for the treatment of hypercholesterolemia, one of the main risk factor for... (Review)
Review
Statins are considered to be safe, well tolerated and the most efficient drugs for the treatment of hypercholesterolemia, one of the main risk factor for atherosclerosis, and therefore they are frequently prescribed medications. The most severe adverse effect of statins is myotoxicity, in the form of myopathy, myalgia, myositis or rhabdomyolysis. Clinical trials commonly define statin toxicity as myalgia or muscle weakness with creatine kinase (CK) levels greater than 10 times the normal upper limit. Rhabdomyolysis is the most severe adverse effect of statins, which may result in acute renal failure, disseminated intravascular coagulation and death. The exact pathophysiology of statin-induced myopathy is not fully known. Multiple pathophysiological mechanisms may contribute to statin myotoxicity. This review focuses on a number of them. The prevention of statin-related myopathy involves using the lowest statin dose required to achieve therapeutic goals and avoiding polytherapy with drugs known to increase systemic exposure and myopathy risk. Currently, the only effective treatment of statin-induced myopathy is the discontinuation of statin use in patients affected by muscle aches, pains and elevated CK levels.
Topics: Animals; Creatine Kinase; Dose-Response Relationship, Drug; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Muscular Diseases; Myositis; Rhabdomyolysis
PubMed: 22001973
DOI: 10.1016/s1734-1140(11)70601-6