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PubMed1997

Inclusion body myositis and paraproteinemia: incidence and immunopathologic correlations.

Serum from 70 patients with sporadic inclusion body myositis (IBM) was subjected to agarose gel immunofixation electrophoresis. The IgG extracted from 9 patients with monoclonal proteins, 3 without, and 2 control subjects and was purified, biotinylated, and applied to muscle biopsy sections for immunocytochemistry and to purified muscle protein fractions for immunoblots. Sixteen of 70 (22.8%) patients with IBM, compared with 2% of age-matched controls, had a monoclonal gammopathy characterized as IgG lambda in 9 patients, IgG kappa in 4, IgM kappa in 2, and IgA lambda in 1. The mean age of IBM patients with gammopathy was 60.6 years (range, 35-77 years), compared with 66.1 years (range, 42-80 years) of the IBM patients without gammopathy. The IgG of the patients, more often than that of the control subjects, immunostained myonuclei and recognized various muscle proteins of 35 to 145 kd. We conclude that IBM, regardless of age, is frequently associated with monoclonal gammopathies, which often recognize various muscle components, especially myonuclei, suggesting disturbed immunoregulation.

Adult↗
PubMed1986

Effect of warfarin sodium therapy on excretion of 4-carboxy-L-glutamic acid in scleroderma, dermatomyositis, and myositis ossificans progressiva.

The effect of warfarin sodium on excretion of calcium, phosphorus, and 4-carboxy-L-glutamic acid (Gla) was studied in 5 patients with ectopic calcification (2 with scleroderma, 1 with dermatomyositis, and 2 with myositis ossificans progressiva). Warfarin reduced urinary excretion of Gla in all patients, but no changes in calcium and phosphorus excretion or in objective parameters of calcinosis were observed during 6-36 months of treatment. Two patients experienced hemorrhagic complications during therapy, emphasizing a hazard of long-term anticoagulation treatment. Since ectopic calcium deposits contain Gla-rich protein, suppression of Gla synthesis by warfarin sodium over a longer period may prevent deposition and allow removal of existing calcinosis deposits.

Adult↗
PubMed1987

Inclusion body myositis presenting as treatment-resistant polymyositis.

Inclusion body myositis (IBM) has been viewed as a distinct and rare form of inflammatory myopathy. Previously reported findings from series of IBM patients have suggested that clinical and pathologic features are present which readily distinguish it from idiopathic polymyositis. We report 4 cases of IBM presenting clinically and pathologically as polymyositis, each of which was refractory to therapy. Our data suggest that IBM may be a more common and heterogeneous form of inflammatory myopathy than has been previously suggested. Furthermore, IBM may be clinically and electrophysiologically indistinguishable from polymyositis. Reasons for failing to recognize IBM by pathologic studies appear to include: the skip lesion nature of the pathologic findings, failure to examine tissues by electron microscopy, and a low level of suspicion or lack of recognition. Because of its insidious clinical course and its failure to respond to immunosuppressive therapy, IBM may be an important variant of treatment-resistant polymyositis.

Adult↗
PubMed1990

Pediatric onset of Behçet's syndrome with myositis: case report and literature review illustrating unusual features.

We report a case of Behçet's syndrome with myositis in a pediatric patient, emphasizing the importance of muscle involvement in the differential diagnosis of calf pain and swelling in Behçet's syndrome. A review of the English-language literature from 1965 to the present suggests that the clinical picture of Behçet's syndrome in children differs from that in adults, in that there is a lower frequency of ocular disease, and unusual manifestations appear to be more common.

Adolescent↗
PubMed2004

Validation and clinical significance of the Childhood Myositis Assessment Scale for assessment of muscle function in the juvenile idiopathic inflammatory myopathies.

OBJECTIVE: To examine the measurement characteristics of the Childhood Myositis Assessment Scale (CMAS) in children with juvenile idiopathic inflammatory myopathy (juvenile IIM), and to obtain preliminary data on the clinical significance of CMAS scores. METHODS: One hundred eight children with juvenile IIM were evaluated on 2 occasions, 7-9 months apart, using various measures of physical function, strength, and disease activity. Interrater reliability, construct validity, and responsiveness of the CMAS were examined. The minimum clinically important difference (MID) and CMAS scores corresponding to various degrees of physical disability were estimated. RESULTS: The intraclass correlation coefficient for 26 patients assessed by 2 examiners was 0.89, indicating very good interrater reliability. The CMAS score correlated highly with the Childhood Health Assessment Questionnaire (C-HAQ) score and with findings on manual muscle testing (MMT) (r(s) = -0.73 and 0.73, respectively) and moderately with physician-assessed global disease activity and skin activity, parent-assessed global disease severity, and muscle magnetic resonance imaging (r(s) = -0.44 to -0.61), thereby demonstrating good construct validity. The standardized response mean was 0.81 (95% confidence interval 0.53, 1.09) in patients with at least 0.8 cm improvement on a 10-cm visual analog scale for physician-assessed global disease activity, indicating strong responsiveness. In bivariate regression models predicting physician-assessed global disease activity, MMT remained significant in models containing the CMAS (P = 0.03) while the C-HAQ did not (P = 0.4). Estimates of the MID ranged from 1.5 to 3.0 points on a 0-52-point scale. CMAS scores corresponding to no, mild, mild-to-moderate, and moderate physical disability, respectively, were 48, 45, 39, and 30. CONCLUSION: The CMAS exhibits good reliability, construct validity, and responsiveness, and is therefore a valid instrument for the assessment of physical function, muscle strength, and endurance in children with juvenile IIM. Preliminary data on MID and corresponding levels of disability should aid in the clinical interpretation of CMAS scores when assessing patients with juvenile IIM.

Adolescent↗
PubMed2004

Normal scores for nine maneuvers of the Childhood Myositis Assessment Scale.

OBJECTIVE: To document and evaluate the scores that normal, healthy children achieve when performing 9 maneuvers of the Childhood Myositis Assessment Scale (CMAS). METHODS: A total of 303 healthy children, 4-9 years of age, were scored as they performed 9 CMAS maneuvers. The data were then evaluated to determine whether normal scores for some maneuvers are age and sex dependent. RESULTS: All children were able to achieve maximum possible scores for the supine to prone, supine to sit, floor sit, floor rise, and chair rise maneuvers. All but 2 4-year-olds achieved a maximum possible score for the arm raise/duration maneuver. Performance of the head lift and sit-up maneuvers varied significantly, depending primarily on age. Children in all age groups had less difficulty performing the leg lift than the head lift or sit-up. CONCLUSION: The normative data generated by this study are of value for interpreting the serial CMAS scores of children with idiopathic inflammatory myopathies.

Child↗
PubMedDate not supplied

Fine needle aspiration cytology of myositis ossificans.

Fine needle aspiration was performed on a large soft tissue mass of the left thigh and hip region in a 27-year-old paraplegic man. Cytologic examination revealed sheets of immature fibroblasts and scattered skeletal muscle cells in various stages of degeneration compatible with myositis ossificans. This case is probably the first needle aspiration cytology of this lesion. The danger of confusing the cytology with that of a sarcoma is emphasized.

Adult↗
PubMed1987

Leukocytapheresis in inclusion body myositis.

A patient with inclusion body myositis was treated with a course of 22 leukocytaphereses combined with prednisone and azathioprine therapy. He improved clinically during an induction phase of frequent cytapheresis, which reduced the circulating levels of T lymphocytes and monocytes and decreased the ratio of the T4+ to T8+ lymphocyte subsets. During subsequent maintenance cytapheresis there was partial recovery of the T4+ population without recovery of T8+ lymphocytes, and the patient lost most of his clinical improvement. In contrast to T lymphocytes and monocytes, there was no persistent reduction in circulating B lymphocyte levels during the course of therapy. T8+ lymphocyte populations may regenerate more slowly than T4+ lymphocytes following depletion with leukocyatpheresis combined with prednisone and azathioprine therapy. A loss of T8+ suppressor relative to T4+ helper-cell function could lead to an intensification of autoimmune conditions.

Humans↗
PubMed2005

Molecular pathology and pathogenesis of inclusion-body myositis.

We summarize the molecular phenotype, diagnostic criteria, and the newest advances related to seeking the pathogenic mechanism(s) of sporadic inclusion-body myositis (s-IBM), a muscle disease usually of persons over age 50. On the basis of our research, several processes seem to be important in relation to the still-speculative pathogenesis: 1) increased transcription and accumulation of amyloid-beta precursor protein (AbetaPP), and accumulation of its proteolytic fragment Abeta; 2) abnormal accumulation of cholesterol, caveolin-1, and apolipoprotein E; 3) oxidative stress; 4) accumulations of intramuscle fiber multiprotein aggregates; and 5) evidence that unfolded/misfolded proteins participate in s-IBM pathogenesis. Our basic hypothesis is that overexpression of AbetaPP within the aging muscle fibers is an early upstream event causing a subsequent pathogenic cascade.

Aging↗
PubMedDate not supplied

MR imaging of myositis ossificans: variable patterns at different stages.

Five patients with a palpable mass at presentation underwent magnetic resonance (MR) imaging. The final diagnosis was myositis ossificans (MO). MR imaging features, particularly after injection of gadopentetate dimeglumine, mimicked those of an inflammatory mass or neoplasm. The lesions were excised in three patients, and the images were correlated with histologic findings. Three different appearances were noted on MR images, corresponding to the stages of maturation of MO. Two cases involved early-stage lesions, and T1-weighted MR images showed a mass with homogeneous intermediate signal intensity. Both lesions showed rim enhancement after contrast agent injection and high signal intensity on T2-weighted images. Pathologic specimens demonstrated stroma with masses of spindle cells in which osteoid production was interspersed. The enhanced rim of the lesion mimicked the expected MR appearance of an abscess or necrotic tumor. Areas of enhancement in adjacent muscle were also seen on postcontrast T1-weighted images. Intermediate-stage MO was present in one case; there was evidence of a thin rim of calcification on plain radiographs and fatty changes in the lesion on T1-weighted images, corresponding with histologic findings. One case of a mature lesion showed a considerable degree of peripheral calcification both on MR images and at histology. MR imaging is nonspecific in the diagnosis of early-stage MO.

Abscess↗
PubMed2006

Camptocormia associated with focal myositis in multiple-system atrophy.

Camptocormia (CC) or pronounced forward flexion of the trunk is a common symptom of Parkinson's disease. We describe 2 patients with probable, respectively possible multiple-system atrophy and CC. Magnetic resonance imaging of the erector trunci showed focal patchy hyperintensities with gadolinium enhancement and muscle biopsy was indicative of variably pronounced focal myositis. CC was progressive and the major handicap for both patients after 1 and 1.5 years of follow-up, respectively. The therapeutic response was poor. Similarities with the dropped-head syndrome suggest that the muscle pathology may be either the primary cause of CC, a focal reaction to the CC posture, or a coincident syndrome of old age.

Aged↗
PubMed2003

Toxoplasmic myositis as a presenting manifestation of idiopathic CD4 lymphocytopenia.

Toxoplasma gondii encysts in skeletal muscle. Although only rarely found at muscle biopsy, this parasite has previously been regarded as a possible cause of polymyositis. We report a case of biopsy-proven toxoplasmic myositis in a non-HIV-infected patient that led to recognition of idiopathic CD4 lymphocytopenia (ICL), a rare condition typically associated with opportunistic infections. Interestingly, the CD25(+) subset that corresponds to the CD4(+) regulatory T cells controlling autoimmune processes was lacking. Steroid and antiprotozoal therapy led to recovery.

Animals↗
PubMed2004

Focal myositis associated with S-1 radiculopathy: report of two cases.

Two cases are described of pseudotumoral calf hypertrophy after laminectomy for a compressive S-1 radiculopathy. The serum creatine kinase (CK) level was normal or mildly elevated. T2-weighted magnetic resonance imaging (MRI) showed calf enlargement, with an increased signal of the medial head of the gastrocnemius muscle. Electromyography revealed fibrillation potentials and positive sharp waves, but no complex repetitive discharges in the affected gastrocnemius muscle, with motor unit potentials having mixed neurogenic and myopathic features. Muscle biopsy revealed a focal myositis associated with some features of denervation. A brief course of corticosteroids was followed by remission clinically and improvement in the MRI findings.

Adult↗
PubMed2001

Patterns of muscle involvement in inclusion body myositis: clinical and magnetic resonance imaging study.

The differential patterns of muscle involvement in the upper and lower limbs in sporadic inclusion body myositis (sIBM) were examined in 18 patients using both quantitative and manual muscle testing as well as magnetic resonance imaging (MRI) in 9 patients. Weakness of the quadriceps femoris and the forearm flexors was present in most patients, but there was considerable variability in the patterns and severity of muscle involvement. MRI disclosed preferential patterns of muscle involvement within functional groups such as the quadriceps femoris, in which there was severe involvement of the vasti with relative sparing of the rectus femoris, and the triceps surae, in which selective involvement of the medial gastrocnemius was common. Involvement of flexor digitorum profundus on MRI was found in only one third of patients. The results emphasize the variability in the clinical phenotype and differential susceptibility of muscles to the disease process in sIBM.

Adult↗
PubMed2006

Evidence for MHC I-restricted CD8+ T-cell-mediated immunopathology in canine masticatory muscle myositis and polymyositis.

Masticatory muscle myositis (MMM) is the most common inflammatory myopathy (IM) in dogs, associated with antibodies against myosin. To further elucidate the immunopathogenesis, we investigated muscles of 53 dogs with MMM, 32 dogs with polymyositis (PM), and 4 dogs suffering from both, with regard to the presence and location of CD4(+) and CD8(+)T cells, B cells, macrophages, major histocompatibility complex (MHC) class I and class II antigens, and autoantibodies. CD8(+)T cells were found in MMM (91%) and PM (75%), mostly paralleled (68% and 61%) by enhanced expression of MHC class I antigen on muscle fibers. CD8(+)T cells invading intact and neighboring necrotic muscle fibers were present in MMM (39%) and PM (42%). Dogs with MMM lacking intramuscular (26%) and circulating (36%) autoantibodies also had CD8(+) T-cell infiltrations and muscle-fiber lesions. Since MHC class I antigen and CD8(+) T cells were detected in the presence of CD4(+) T cells, regardless of antimuscular antibodies, we consider MMM and PM in the dog as a CD8(+) T-cell-mediated immunopathological disease that initiates muscle-fiber destruction and leads to production of myosin autoantibodies.

Animals↗
PubMed2006

Nuclear membrane proteins are present within rimmed vacuoles in inclusion-body myositis.

The rimmed vacuoles within muscle in inclusion-body myositis (IBM) are structures of uncertain origin. Two hypotheses have been proposed for their formation: that they develop as a consequence of abnormal lysosomal function or in association with the breakdown of myonuclei. We tested the latter hypothesis by studying muscle samples from 14 patients with IBM and 18 controls using immunohistochemistry for nuclear membrane proteins, examining semithin sections, and performing electron microscopy. We found that in IBM muscle vacuoles were immunoreactive for the inner nuclear membrane proteins emerin and lamin A/C. Myonuclei with fragmented or focally absent nuclear membranes were present in immunohistochemical and electron microscopy studies. The association of nuclear membrane proteins with rimmed vacuoles confirms the hypotheses that rimmed vacuoles in IBM form in association with myonuclear pathology and that IBM differs from other inflammatory myopathies in that abnormalities of myonuclei are more prominent.

Dystrophin↗
PubMed2007

Myeloid dendritic cells in inclusion-body myositis and polymyositis.

Dendritic cells (DCs), immune system cells central to the development of immunity, have not previously been reported in muscle in inclusion-body myositis (IBM). We performed immunohistochemical studies on muscle biopsy specimens from 50 patients using monoclonal antibodies that distinguish two classes of DCs, myeloid DC and plasmacytoid DC. In 17 of 20 IBM and 9 of 10 polymyositis (PM) specimens, myeloid DCs were present in substantial numbers, frequently surrounded and sometimes invading otherwise intact myofibers, and were part of dense collections of cells that included T cells. Dermatomyositis muscle had more plasmacytoid DCs than myeloid DCs, whereas IBM and PM had greater numbers of myeloid DCs. The stellate morphology of myeloid DCs in dense collections of cells that included T cells suggests local intramuscular antigen presentation in IBM and PM.

Antibodies, Monoclonal↗