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Query: UMLS:C1762617 (weakness)
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Inflammatory myopathies can be subdivided into two main groups: infectious (bacterial, viral or other) myositis and immunogenic myositis. According to their frequency there are four main groups of diseases: dermatomyositis (DM), overlap syndromes, inclusion body myositis (IBM), idiopathic polymyositis (PM). Muscle weakness and atrophy are the prominent clinical symptoms of all immunogenic inflammatory myopathies. Muscle pain is not so common and occurs more frequently in acute forms than in chronic cases. Primary chronic forms of polymyositis and inclusion body myositis are mostly painless. Diagnosis starts with electromyography and laboratory investigations (especially CK). Myositis associated antibodies are mostly associated with acute forms. Radiological methods, especially MRI, are important in chronic cases. Definite diagnosis has to be done by muscle biopsy. Immunohistological (especially in DM and PM) and ultrastructural (especially in IBM) techniques are necessary in some cases. Concerning therapy of DM and PM, corticosteroids in combination with immunosuppressive drugs are effective in most cases. Intravenous immunoglobulins are needed only in selected cases (severe forms), side effects of therapy or resistance to conventional therapy. In IBM, it is the only therapeutic possibility, especially in young patients with rapid progression of the disease.
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PMID:[Importance of inflammatory myopathies in practice]. 1464 16

The relative scarcity of inclusion-affected muscle cells or markers of cell death in inclusion body myositis (IBM) is in distinction to the specific and early intracellular deposition of several Alzheimer's Disease (AD)-related proteins. The current study examined the possible correlation between myotube beta-amyloid and/or Tau accumulations and a widespread mishandling of intracellular muscle calcium concentration that could potentially account for the unrelenting weakness in affected patients. Cultured myogenic cells (C(2)C(12)) expressed beta-amyloid-42 (Abeta(42)) and fetal Tau peptides, as human transgenes encoded by herpes simplex virus, either individually or concurrently. Co-expression of Abeta(42) in C(2)C(12) myotubes resulted in hyperphosphorylation of Tau protein that was not observed when Tau was expressed alone. Resting calcium concentration and agonist-induced RyR-mediated Ca(2+) release were examined using calcium-specific microelectrodes and Fluo-4 epifluorescence, respectively. Co-expression of Abeta(42) and Tau cooperatively elevated basal levels of myoplasmic-free calcium, an effect that was accompanied by depolarization of the plasma membrane. Sarcoplasmic reticulum (SR) calcium release, induced by KCl depolarization, was not affected by Abeta(42) or Tau. In contrast, expression of Abeta(42), Tau, or Abeta(42) together with Tau resulted in enhanced sensitivity of ryanodine receptors to activation by caffeine. Notably, expression of beta-amyloid, alone, was sufficient to result in an increased sensitivity to direct activation by caffeine. Current results indicate that amyloid proteins cooperate to raise resting calcium levels and that these effects are associated with a passive SR Ca(2+) leak and Tau hyperphosphorylation in skeletal muscle.
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PMID:Calcium dyshomeostasis in beta-amyloid and tau-bearing skeletal myotubes. 1538 69

We report the first case of inclusion body myositis (IBM) which occurred after interferon-alpha treatment for chronic hepatitis C. A 63-year-old man contracted hepatitis C virus (HCV) and human T cell leukemia virus type 1 (HTLV-1) from a blood transfusion at age of 18. At age 57, he was treated with interferon-alpha (IFN alpha) for chronic hepatitis C. A month later, he developed muscle weakness in the proximal part of his lower extremities. IBM was diagnosed after a muscle biopsy at age 62. Steroid therapy improved his muscle power. One year later, worsening of his hepatic condition required re-administration of IFN alpha after gradual decrease and discontinuation of prednisolone. However, several days later, he rapidly became weaker and required a cane to walk. Elevated serum creatine kinase (2,199IU/L) and abnormal intensity in his MRI of thigh were demonstrated. The second muscle biopsy, performed after obtaining the informed consent from our patient, confirmed relapse of IBM. His symptoms improved again after discontinuation of IFN alpha and re-induction of prednisolone. Although a few cases each of IBM associated with HCV or HTLV-1 have been reported, the pathogenesis of virus-associated inflammatory myositis has not been clearly understood. Moreover, there has been no description on IBM associated with IFN alpha treatment, though several cases of polymyositis have been reported. Our case suggests that infection of HCV and HTLV-1 may be immunologically involved in the development of IBM and that IFN alpha can be directly related to onset and relapse of IBM.
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PMID:[Inclusion body myositis after interferon-alpha treatment in a patient with HCV and HTLV-1 infection]. 1551 4

Myosin, a molecular motor, converts chemical energy into mechanical force. The motor domain of myosin heavy chain (MyHC) includes an ATP binding region with ATPase activity and an actin-binding region. Motor function is achieved by conformational changes, at hydrolysis, of ATP causing a shift in the angle between the actin binding head and the rod region of the molecule. The elongated alpha-helical coiled-coil rod region of MyHC molecules constitutes the major part of the thick filaments of the sarcomere. Three major MyHC isoforms are expressed in human skeletal muscle (type I, MYH7, expressed in type 1 fibres; IIa, MYH2, expressed in 2A fibres; IIx, MYH1, expressed in 2B fibres). While mutations in slow/beta cardiac MyHC (MYH7) are a common cause of familial hypertrophic cardiomyopathy, no skeletal myopathies have, until recently, been associated with mutations in MyHC. A heterozygous mutation, Glu706Lys, in the core of the head of MyHC IIa is associated with a familial congenital myopathy, which, in most instances, has shown mild phenotypic expression in children but progressive course in some adults. There is a relationship between the level of expression of mutated MyHC IIa and muscle pathology. Some adults with a progressive course show muscle fibres with rimmed vacuoles and filaments of the type seen in inclusion body myositis/myopathy (IBM). Endurance training in a group of affected patients caused a shift in the expression of myosin from fast (IIx) to slow (I) isoforms but no reduction in the expression of MyHC IIa. A heterozygous mutation, Arg1845Trp, in the distal rod region of slow myosin (type I, MYH7) is associated with familial congenital myopathy, with large deposits of MyHC I in the subsarcolemmal region of type 1 muscle fibres, "Myosin storage myopathy". These patients showed slowly progressive muscle weakness but no overt cardiomyopathy. These two muscle diseases, which are caused by mutations in MyHC, form the basis of a novel entity: "Myosin myopathies".
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PMID:Myopathies associated with myosin heavy chain mutations. 1560 50

COMMON ELEMENTS: Primary inflammatory myopathies consist of dermatomyositis (DM), polymyositis (PM) and inclusion body myositis (IBM). They have certain characteristics in common: progressive muscle weakness and mononuclear inflammatory infiltrates in the muscle. DIFFERENT MECHANISMS: They may be distinguished by their histological features which also reflect their different underlying pathogeneses. The mechanism of DM would be complement-mediated microangiopathy, the inflammatory infiltrate of which would be secondary to ischemic phenomena, whereas in PM the muscle fibres are damaged by cytotoxic CD8 T lymphocytes. The factors triggering-off these two forms of myositis remain unknown. IBM may be a degenerative disease with accumulation of a variety of proteins within the fibres. The inflammatory infiltrate, which is similar to that seen in PM, may be a reaction to accumulated proteins.
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PMID:[Pathogenesis of primary inflammatory myopathies]. 1561 79

Polymyositis, dermatopolymyositis, and inclusion body myositis imply chronic inflammation of skeletal muscles. Pulmonary complications include aspiration pneumonia, interstitial pneumonitis, or respiratory muscle myositis. This study aims at better describing their impact on respiratory muscle. Twenty-three consecutive patients (12 PM, 5 DM, 6 IBM) were studied (static inspiratory and expiratory pressures; diaphragm function in terms of the mouth and transdiaphragmatic pressure responses to bilateral phrenic stimulation). Pulmonary parenchymatous abnormalities were mild (6 cases) or absent. The mouth pressure produced by phrenic stimulation was 6.83+/-3.01 cm H2O, with 18 patients (78%) diagnosed with diaphragm weakness (<10 cm H2O) and lower values in DM (4.35+/-1.48 cm H2O) than in IBM and in PM (P<0.05). Diaphragm weakness is frequent and probably overlooked in inflammatory myopathies. Further studies are needed to delineate the clinical relevance of these results.
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PMID:Diaphragmatic dysfunction in patients with idiopathic inflammatory myopathies. 1563 18

We report on a 16-year-old girl with a unique neuromuscular disorder characterised by progressive proximal muscle weakness and numerous tubular aggregates, intracytoplasmic, as well as intranuclear inclusions of the IBM type in her muscle biopsy. The clinical features of the presented case, as manifested by the early childhood onset of the disease, proximal weakness, lumbar hyperlordosis, and bilateral Achilles tendon contractures, were suggestive of congenital myopathy. To the best of our knowledge, the coexistence of tubular aggregates and tubulofilamentous inclusions of the IBM type in a child has never been described.
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PMID:Congenital myopathy with tubular aggregates and tubulofilamentous IBM-type inclusions. 1577 20

Five patients with untreated dermatomyositis, five with inclusion body myositis, and 16 healthy elderly volunteer subjects (controls) underwent open (dermatomyositis and inclusion body myositis) or percutaneous (controls) muscle biopsy. Biopsied muscles included deltoid, biceps and vastus lateralis. Chemically skinned single muscle fibers were activated with Ca(+2); the slack test was performed to determine maximal unloaded shortening velocity (Vo). Parameters measured include single fiber cross sectional area, maximal force, specific force and Vo. 429 Type I and 94 Type IIA fibers were studied. Cross sectional area and maximal force were greater in inclusion body myositis than dermatomyositis or control for Type I and IIA fibers. Specific force of Type I fibers was similar in inclusion body myositis and dermatomyositis but greater than in controls. Vo was greater in Type I, but not IIA, fibers in dermatomyositis compared with inclusion body myositis and controls. The force and velocity generating capacity of single muscle fibers is preserved in patients with dermatomyositis and inclusion body myositis suggesting that dysfunction of the contractile proteins does not contribute to clinical muscle weakness.
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PMID:Preservation of in vitro muscle fiber function in dermatomyositis and inclusion body myositis: a single fiber study. 1583 27

The clinical features of inclusion body myositis (IBM) were of minor importance in the design of consensus diagnostic criteria, mainly because of controversial views on the specificity of signs and symptoms, although some authors reported "typical" signs. To re-assess the clinical spectrum of IBM, a single investigator using a standard protocol studied a cohort of 64 patients cross-sectionally. Symptom onset was before the age of 50 years in 20% of cases. Only a few patients (14 %) started with weakness other than that of quadriceps, finger flexor or pharyngeal muscles. The sequence of power loss was erratic, but onset of symptoms with quadriceps weakness predicted an earlier onset of dysphagia in older patients (> or = 56 years) compared with younger ones (< 56 years) (p = 0.02). Despite widespread weakness patients had favourable scores on three commonly used function scales and they kept their employment. Complete wheel-chair dependency was rare (3 %). A dominant characteristic was the anatomical distribution of afflicted muscles: ventral extremity muscle groups were more affected than dorsal muscle groups and girdle muscles were least affected, the latter preserving postural stability. Ankylosis, especially in extension of the fingers,was frequently present. Together with the sparing of intrinsic hand muscles it was helpful in the preservation of many skillful movements. IBM has a unique distribution of muscle weakness. Ankylotic contractures are common. We feel that their joint impact on daily functioning is characteristic for the disease.
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PMID:Inclusion body myositis. Clinical features and clinical course of the disease in 64 patients. 1594 3

Cardiac troponin T (cTnT) is considered as a specific marker for acute myocardial infarction. Here, we present a case with elevated cTnT, determined by a third-generation assay, without signs of a myocardial lesion. Routine investigation of a 66-year-old female patient with indolent B-cell lymphoma revealed increased serum levels of creatine kinase (CK), MB fraction of CK (CK-MB), and cTnT, although she did not complain of cardiac symptoms. Electrocardiographic monitoring, echocardiography, magnetic resonance computed angiography, and percutaneous coronary angiography excluded myocardial damage. However, the close follow-up showed a steady increase of CK-MB and cTnT levels and gradual development of weakness in both thighs. A biopsy of the right quadriceps muscle led to the diagnosis of inclusion body myositis. In contrast to cTnT, cardiac troponin I could not be detected retrospectively in any of her serum samples. These results demonstrate for the first time that cTnT is elevated in patients with inclusion body myositis.
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PMID:Positive troponin T without cardiac involvement in inclusion body myositis. 1699 78


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