Necrotic Muscle Fibers Research Articles

Roles of ADAM8 in elimination of injured muscle fibers prior to skeletal muscle regeneration

Skeletal muscle regeneration requires processes different from developmental myogenesis. One important difference is a requirement of inflammatory reactions prior to regenerative myogenesis, by which injured muscle fibers must be eliminated to make new myotubes. In this study, we show that efficient elimination of injured muscle fibers during regeneration requires ADAM8, a member of a disintegrin and metalloprotease (ADAM) family. Skeletal muscle of dystrophin-null mice, an animal model for Duchenne Muscular Dystrophy, deteriorates by the lack of ADAM8, which is characterized by increased area of muscle degeneration and increased number of necrotic and calcified muscle fibers. Adam8 is highly expressed in neutrophils. Upon cardiotoxin-induced skeletal muscle injury, neutrophils invade into muscle fibers through the basement membrane and form large clusters in wild type, but not in ADAM8-deficient mice, although neutrophils of the latter infiltrate into interstitial tissues similarly to those of wild type mice. Neutrophils lose their adhesiveness to blood vessels after infiltration, which includes an ectodomain shedding of P-Selectin Glycoprotein Ligand-1 (PSGL-1) on their surface. Expression of PSGL-1 on the surface of neutrophils remains higher in ADAM8-deficient than in wild type mice. These results suggest that ADAM8 mediates an enhanced invasiveness of neutrophils into injured muscle fibers by the removal of their adhesiveness to blood vessels after infiltration into interstitial tissues.

Decreased eccentric exercise-induced macrophage infiltration in skeletal muscle after supplementation with a class of ginseng-derived steroids.

Dammarane steroids (DS) are a class of chemical compounds present in Panax ginseng. Here, we evaluated the effect of 10 weeks of DS supplementation on inflammatory modulation in the soleus muscle following eccentric exercise (EE)-induced muscle damage (downhill running). Eighty rats were randomized into 4 groups of DS supplementation (saline, 20, 60, 120 mg/kg body weight). Inflammatory markers were measured at rest and again 1 h after EE. At rest, NFκB signaling, TNF-alpha and IL-6 mRNAs, 3-nitrotyrosine, glutathione peroxidase, and GCS (glutamylcysteine synthetase) levels were significantly elevated in the skeletal muscle of DS-treated rats in a dose-dependent manner. Additionally, there were no detectable increases in the number of necrotic muscle fibers or CD68+ M1 macrophages. However, muscle strength, centronucleation, IL-10 mRNA expression, and the number of CD163+ M2 macrophages increased significantly over controls with DS treatment in rat soleus muscle. Under EE-challenged conditions, significant increases in muscle fiber necrosis, CD68+ M1 macrophage distribution, and 3-nitrotyrosine were absent in rats that received low and medium doses (20 and 60 mg/kg) of DS treatment, suggesting that DS possess anti-inflammatory action protecting against a muscle-damaging challenge. However, this protective activity was diminished when a high dose of DS (120 mg/kg) was administered, suggesting that DS possess hormetic properties. In conclusion, our study provides new evidence suggesting that DS is an ergogenic component of ginseng that potentiate inflammation at baseline but that produce anti-inflammatory effects on skeletal muscle following muscle-damaging exercise. Furthermore, high doses should be avoided in formulating ginseng-based products.

Could Exon Skipping Help Dystrophic Boys to Run, Hop, and Jump?

Could Exon Skipping Help Dystrophic Boys to Run, Hop, and Jump?

Muscle biopsy features of idiopathic inflammatory myopathies and differential diagnosis

The gold standard to characterize idiopathic inflammatory myopathies is the morphological, immunohistochemical and immunopathological analysis of muscle biopsy. Mononuclear cell infiltrates and muscle fiber necrosis are commonly shared histopathological features. Inflammatory cells that surround, invade and destroy healthy muscle fibers expressing MHC class I antigen are the typical pathological finding of polymyositis. Perifascicular atrophy and microangiopathy strongly support a diagnosis of dermatomyositis. Randomly distributed necrotic muscle fibers without mononuclear cell infiltrates represent the histopathological hallmark of immune-mediated necrotizing myopathy; meanwhile, endomysial inflammation and muscle fiber degeneration are the two main pathological features in sporadic inclusion body myositis. A correct differential diagnosis requires immunopathological analysis of the muscle biopsy and has important clinical implications for therapeutic approach. In particular, unnecessary, potentially harmful, immune-suppressive therapy should be avoided alike in dystrophic myopathies with secondary inflammation.

G.P.73: Necrotizing autoimmune myopathy: Clinical and histopathological features of 6 patients

Necrotizing autoimmune myopathy (NAM) is a relatively newly recognized subgroup of idiopathic inflammatory myopathies. Classically, patients present with a subacute severe proximal myopathy, associated with a markedly elevated creatine kinase level, usually greater than 10 times the upper limit of normal, and electromyography shows myopathic changes. Muscle biopsy is required for diagnosis, revealing active necrosis of the muscle fibers without inflammatory invasion and variable upregulation of MHC class 1. The other causes of necrotizing myopathy should be excluded such as toxic myopathies, muscular dystrophies. The clinical presentation is highly variable, often similar to the other inflammatory myopathies. We herein report the clinical and histopathological features of 6 patients with NAM. Age of onset ranged from 35 to 69 years (mean 56.8 years), and 5 of them were female. All of the patients presented with subacute onset proximal limb weakness, 4 with myalgia. Serum CK levels ranged from 1041 to 7900 IU/L. Needle EMG revealed myopathic changes in all. Muscle biopsies showed mainly necrotic and/or regenerative muscle fibers in all 6 patients. There were focal (in 4) or diffuse (in 2) major histocompatibility complex class 1 expression in sarcolemma or cytoplasm of muscle fibers among necrotic muscle fibers. Screening for cancer revealed negative or normal results in all. Two patients received statins previously. Three patients had diabetes mellitus and 1 patient had SLE. All treated with steroids and/or immunosuppressive drugs. The clinical characteristics of these patients, pathologic findings, associated risk factors and response to immunosuppressive therapies are discussed.

G.P.88: Novel inhibitor of hematopoietic prostaglandin D synthase improves the muscle disorder in an experimental model of Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a fatal genetic disease. The fibers of muscle in DMD patients easily suffer necrotic change, because of the loss of dystrophin. Thus the patients present with a weakening motor activity. There is still no complete cure for the disease. Recently, we have reported that prostaglandin D2 (PGD2) synthesized by hematopoietic PGD synthase (HPGDS) may play an important role in the pathology of DMD. In this study, we evaluated the beneficial effects of a highly selective HPGDS inhibitor (TAS-205 which is found in our laboratory) in dystrophin-deficient mice. We used dystrophin-deficient mdx mice (C57BL/6 back ground) and the wild-type mice (C57BL/6). Mice were treated with TAS-205 daily by supplied the diet including 0.01% or 0.1% TAS-205 from 5 to 9 weeks of age. Mice of control group and normal group were supplied the same food without drug. At 9 weeks of age, we measured the locomotor activity during night-time, collected the mouse urine of at night-time to determine the urinary concentration of tetranor-PGDM, a metabolite of PGD2, and evaluated the rate of necrotic fibers area in cross sections of the diaphragm muscle. The locomotor activity at the night-time was significantly lower in mdx mice than that in wild-type mice. In histological evaluation, many necrotic fibers were detected in diaphragm muscle of mdx mice but hardly in wild-type mice. The urinary tetranor-PGDM concentration was significantly higher in mdx mice than that in wild-type mice. TAS-205 dose-dependently suppressed the urinary tetranor-PGDM amount in mdx mice. TAS-205 at high dose significantly reduced the necrotic muscle fibers and recovered the locomotor activity in mdx mice. These results indicate that PGD2 synthesized by HPGDS is involved in the progression of muscular necrosis in DMD and a HPGDS inhibitor, such as TAS-205, would be an effective therapy for DMD.

Poster 13 Assessment of the Application of Exercise Prescription for Physical Medicine and Rehabilitation Resident Physicians During Medical Training

exacerbated with toe walking. Examination revealed supple leg compartments with diffuse posterior calf tenderness. Leg strength, sensation, reflexes, pulses, and skin were normal. Leg radiographs and ultrasound showed only mild subcutaneous edema. Superficial and deep posterior leg compartment pressure measurements were normal. Erythrocyte sedimentation rate and C-reactive protein were elevated and anti-nuclear antibodies weakly positive. Bilateral leg MRI showed diffuse patchy areas of increased T2 signal involving the muscles and subcutaneous tissues of all leg compartments. Electromyography showed borderline short duration, low amplitude motor units in multiple calf muscles.A lateral gastrocnemius biopsy demonstrated scattered necrotic muscle fibers and heavy inflammatory exudate, consistent with a severe, active, immunemediated inflammatory myopathy. Setting: Sports Medicine Clinic Results or Clinical Course: With the diagnosis confirmed, oral prednisone (40 mg QD) was initiated and tapered to discontinuation over 14 weeks. Leg pain and swelling quickly improved, and she returned to jogging pain-free within a few weeks. After 8 weeks, she was released to high-intensity activity and returned to soccer practice without difficulty. Discussion: Inflammatory myopathy (IM) is an uncommon cause of acute leg pain in athletes. An atraumatic onset of leg pain and tenderness should raise suspicion for IM. MRI can be helpful in making the diagnosis and guiding a biopsy. There is emerging evidence that moderate-intensity aerobic and resistance exercise is safe and beneficial in IM. However, no studies to date have addressed return to play guidelines for athletes with this condition. Conclusions: IM should be considered in the differential diagnosis for acute leg pain. MRI can be helpful for diagnosis. This case demonstrates that return to high-intensity contact sport is possible with IM, but more research is needed to inform return to play decisions.

Activated IL-22 pathway occurs in the muscle tissues of patients with polymyositis or dermatomyositis and is correlated with disease activity

The aim of this study was to assess the expression of IL-22, IL-22 receptor 1 (IL-22R1), IL-22 binding protein (IL-22BP) and p-STAT3 in muscle tissue from patients with PM and DM. Levels of IL-22, IL-22R1, IL-22BP and STAT3 mRNA were quantified by RT-PCR. The expression of IL-22, IL-22R1, IL-22BP and p-STAT3 was also analysed using immunohistochemistry. Significant modulation of the IL-22 pathway was observed in inflammatory myopathic tissues. In particular, a significant overexpression of IL-22 at the protein but not the mRNA level was observed in PM/DM tissues and was correlated with myositis activity. IL-22R1 aberrant expression was also observed among infiltrating mononuclear cells and necrotic muscle cells. IL-22BP, which inhibits IL-22 signalling, was expressed only in some muscle fibres in PM/DM patients. Our findings indicate that the IL-22 pathway is activated in inflammatory myopathic tissues and may be involved in the induction of muscle inflammatory processes and muscle necrosis.

Muscle Disease

On the basis of strong research evidence, Duchenne muscular dystrophy (DMD), the most common severe childhood form of muscular dystrophy, is an X-linked recessive disorder caused by out-of-frame mutations of the dystrophin gene. Thus, it is classified asa dystrophinopathy. The disease onset is before age 5 years. Patients with DMD present with progressive symmetrical limb-girdle muscle weakness and become wheelchair dependent after age 12 years. (2)(3). On the basis of some research evidence,cardiomyopathy and congestive heart failure are usually seen in the late teens in patients with DMD. Progressive scoliosis and respiratory in sufficiency often develop once wheelchair dependency occurs. Respiratory failure and cardiomyopathy are common causes of death, and few survive beyond the third decade of life. (2)(3)(4)(5)(6)(7). On the basis of some research evidence, prednisone at 0.75 mg/kg daily (maximum dose, 40 mg/d) or deflazacort at 0.9 mg/kg daily (maximum dose, 39 mg/d), a derivative of prednisolone (not available in the United States), as a single morning dose is recommended for DMD patients older than 5 years, which may prolong independent walking from a few months to 2 years. (2)(3)(16)(17). Based on some research evidence, treatment with angiotensin-converting enzyme inhibitors, b-blockers, and diuretics has been reported to be beneficial in DMD patients with cardiac abnormalities. (2)(3)(5)(18). Based on expert opinion, children with muscle weakness and increased serum creatine kinase levels may be associated with either genetic or acquired muscle disorders (Tables 1 and 3). (14)(15)

Fulminant systemic capillary leak syndrome due to C1 inhibitor deficiency complicating acute dermatomyositis: a case report

IntroductionDermatomyositis is a chronic inflammatory disorder characterized by muscular and dermatologic symptoms with variable internal organ involvement. This is the first report on a patient with acute dermatomyositis and fulminant systemic capillary leak syndrome.Case presentationA 69-year-old Caucasian woman with chronic dermatomyositis presented with clinical signs of severe hypovolemic shock and pronounced hemoconcentration (hematocrit, 69%). Her colloid osmotic pressure was 4.6mmHg. Following a bolus dose of prednisolone (500mg), fluid resuscitation was initiated. During volume loading, anasarca and acute respiratory distress rapidly developed. Echocardiography revealed an underfilled, hypokinetic, diastolic dysfunctional left ventricle with pericardial effusion but no signs of tamponade. Despite continued fluid resuscitation and high-dosed catecholamine therapy, the patient died from refractory shock 12 hours after intensive care unit admission. A laboratory analysis of her complement system suggested the presence of C1 inhibitor deficiency as the cause for systemic capillary leakage. The post-mortem examination revealed bilateral pleural, pericardial and peritoneal effusions as well as left ventricular hypertrophy with patchy myocardial fibrosis. Different patterns of endomysial/perimysial lymphocytic infiltrations adjacent to degenerated cardiomyocytes in her myocardium and necrotic muscle fibers in her right psoas major muscle were found in the histological examination.ConclusionsThis case report indicates that acute exacerbation of chronic dermatomyositis can result in a fulminant systemic capillary leak syndrome with intense hemoconcentration, hypovolemic shock and acute heart failure. In the presented patient, the cause for diffuse capillary leakage was most probably acquired angioedema, a condition that has been associated with both lymphoproliferative and autoimmunologic disorders.

Myopathy with anti-signal recognition particle antibodies: Clinical and histopathological features in Chinese patients

Myopathy with anti-signal recognition particle antibodies (SRP) is generally thought to be immune-mediated necrotic myopathy in previous studies. We report the clinical and histopathological features of myopathy with anti-SRP antibodies in Chinese patients. Muscle biopsy and immunoblots for myositis antibodies were carried out in 123 patients with idiopathic inflammatory myopathy. Among them, 16 (13.0%) patients had anti-SRP antibodies. Age of onset ranged from 24 to 77years, and the disease began insidiously. Fourteen of 16 patients presented with chronic progression of proximal limb weakness, with 6 having myalgia. Serum creatine kinase levels ranged from 400 to 9082IU/L. Muscle biopsies showed necrotic and/or regenerative muscle fibers in all 16, infiltrates of lymphocytes in 11 and morphological features of muscular dystrophy in 7. Eleven patients showed focal or diffuse major histocompatibility complex class 1 expression in sarcolemma or cytoplasm of muscle fibers, with 9 showing deposition of membrane attack complex in necrotic muscle fibers and 2 around capillaries. These findings indicate that anti-SRP antibodies are most likely to be related to IMNM. Myopathy with anti-SRP antibodies is not infrequent in Chinese patients with idiopathic inflammatory myopathy.

Scleroderma-polymyositis overlap syndrome versus idiopathic polymyositis and systemic sclerosis: a descriptive study on clinical features and myopathology.

IntroductionThe objective was to characterize the clinical and myopathologic features of patients with scleroderma-polymyositis (SSc-PM) overlap compared with a population of patients with systemic sclerosis (SSc) and polymyositis (PM).MethodsA three-way comparison of patients with SSc-PM overlap (n = 25) with patients with SSc (n = 397) and PM (n = 40) on clinical and myopathologic features and causes of death. One neuropathologist blinded for the diagnosis evaluated all recent available muscle biopsies. Biopsies were scored for presence of inflammation, necrotic muscle fibers, rimmed vacuoles, fibrosis, and immunohistochemical staining. Clinical or myopathologic characteristics were compared by using the χ2 test or one-way analysis of variance (ANOVA).ResultsThe prevalence of SSc-PM overlap in the Nijmegen Systemic Sclerosis cohort was 5.9%. The mortality was 32% (eight of 25) in SSc-PM, of which half was related to cardiac diseases. The prevalence of pulmonary fibrosis was significantly increased in SSc-PM (83%) (P = 0.04) compared with SSc (49%) and PM (53%). SSc or myositis-specific antibodies were nearly absent in the SSc-PM group. In almost all biopsies (96%) of SSc-PM patients, necrotic muscle fibers were present, which was significantly increased compared with PM patients (P = 0.02).ConclusionsPatients with SSc-PM have increased prevalence of pulmonary fibrosis and cardiac disease as the cause of death compared with patients with SSc and PM . In addition, we found that necrotizing muscle fibers with inflammation characterize SSc-PM overlap in muscle biopsies. Further research should focus on underlying mechanisms causing necrosis, inflammation, and fibrosis and their relation to pulmonary involvement and mortality in patients with SSc-PM overlap.

Immune-mediated myopathy related to anti 3-hydroxy-3-methylglutaryl-coenzyme A reductase antibodies as an emerging cause of necrotizing myopathy induced by statins

Immune-mediated necrotizing myopathy (IMNM) associated with statin use and anti 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibody is a new and emerging entity that supports a link between statin use and IMNM and raises the questions of distinct clinical phenotypes and treatment strategy. We describe the clinical and histopathological characteristics of a patient and discuss the spectrum of IMNM and statin-induced myopathies. A 65-year-old man was suffering from proximal muscle weakness and elevated CK levels, following exposure to statin therapy. The symptoms worsened despite discontinuation of the drug. At that point, no myositis-specific or -associated antibodies were detected. Malignancy screening did not reveal abnormalities. Muscle biopsy demonstrated a predominantly necrotizing myopathy with minimal lymphocytic infiltrates, MHC class I expression in necrotic muscle fibers, and complement deposition on scattered non-necrotic muscle fibers. Muscle protein analysis by western blot was normal. The patient did not improve with steroid and methotrexate and required monthly intravenous immunoglobulin (IVIG) therapy. Muscle strength gradually improved, CK levels normalized and IVIG were stopped 1year later. Screening for anti-HMGCR antibodies, not available at the time of presentation, was highly positive. Identification of anti-HMGCR antibodies in statin-exposed patients with myopathy appears to be helpful both for differential diagnosis and for treatment strategy. In patients who did not improve after discontinuation of the statin treatment, a muscle biopsy should be performed as well as screening for anti-HMGCR antibodies. Patients with this disorder require aggressive immunosuppressive treatment.

Human β-defensin-3 correlates with muscle fibre degeneration in idiopathic inflammatory myopathies

Sporadic inclusion body myositis (sIBM) and polymyositis (PM) are characterized by muscle inflammation, with sIBM showing additional degenerative alterations. In this study we investigated human beta defensins and associated TLRs to elucidate the role of the innate immune system in idiopathic inflammatory myopathies (IIM), and its association with inflammatory and degenerative alterations. Expression levels of human beta-defensin (HBD)-1, HBD-2, HBD-3 and TLR2, 3, 4, 7 and 9 were analysed by quantitative real-time PCR in skeletal muscle tissue. Localization of HBD-3, collagen 6, dystrophin, CD8-positive T-cells, CD-68-positive macrophages, β-amyloid, the autophagy marker LC3, and TLR3 were detected by immunofluorescence and co-localization was quantified. HBD-3 and all TLRs except for TLR9 were overexpressed in both IIM with significant overexpression of TLR3 in sIBM. HBD-3 showed characteristic intracellular accumulations near deposits of β-amyloid, LC3 and TLR3 in sIBM, and was detected in inflammatory infiltrations and macrophages invading necrotic muscle fibres in both IIM. The characteristic intracellular localization of HBD-3 near markers of degeneration and autophagy, and overexpression of endosomal TLR3 in sIBM hint at different pathogenetic mechanisms in sIBM compared with PM. This descriptive study serves as a first approach to the role of the innate immune system in sIBM and PM.

Can human cord blood-derived stem cells improve statin-induced myopathy in rats? A histological and immunohistochemical study

Background and aim of work Primary myopathies of skeletal muscle are diseases with worldwide prevalence for which effective treatment is urgently needed. The aim of this study was to investigate the ability of human umbilical cord blood (HUCB) stem cells to repair damaged skeletal muscle in a rat model of statin-induced myopathy. Materials and methods This study included 24 adult male albino rats divided equally into four groups: the control group; the myopathy group in which myopathy was induced by administration of simvastatin (80▒mg/kg/day orally for 6 weeks); the stem cell-treated myopathy group in which myopathy was induced by administration of simvastatin with subsequent local injection of 1×106 HUCB stem cells in the right gastrocnemius; and the untreated myopathy group in which myopathy was induced by administration of simvastatin and then left without treatment for 2 weeks. Specimens of the right gastrocnemius from all rats were prepared, sectioned, and subjected to H&E, Prussian blue, and Masson’s trichrome stains in addition to immunohistochemical staining for α smooth muscle actin to reveal myofibroblasts. The area% of collagen and muscle fibers and the number of myofibroblasts/high-power field were ascertained. All measurements were statistically analyzed. Results The gastrocnemius of the myopathy group showed frequent necrotic and damaged muscle fibers, which were replaced by fibrous and fatty tissues. Compared with control rats, there was significant decrease in the area% of muscle fibers and significant increase in the area% of collagen and in the number of myofibroblasts. Two weeks later, there was partial repair of the muscle with no significant differences between stem cell-treated and untreated myopathy groups, which reflects the failure of stem cells to repair damaged myofibers. Conclusion HUCB stem cells have poor therapeutic effect for myopathy and might be hindered by the complex environment of a severely inflamed and degenerated muscle.

Immune-Mediated Necrotizing Myopathy Is Characterized by a Specific Th1-M1 Polarized Immune Profile

Immune-mediated necrotizing myopathy (IMNM) is considered one of the idiopathic inflammatory myopathies, comprising dermatomyositis, polymyositis, and inclusion body myositis. The heterogeneous group of necrotizing myopathies shows a varying amount of necrotic muscle fibers, myophagocytosis, and a sparse inflammatory infiltrate. The underlying immune response in necrotizing myopathy has not yet been addressed in detail. Affected muscle tissue, obtained from 16 patients with IMNM, was analyzed compared with eight non-IMNM (nIMNM) tissues. Inflammatory cells were characterized by IHC, and immune mediators were assessed by quantitative real-time PCR. We demonstrate that immune- and non-immune-mediated disease can be distinguished by a specific immune profile with significantly more prominent major histocompatibility complex class I expression and complement deposition and a conspicuous inflammatory infiltrate. In addition, patients with IMNM exhibit a strong type 1 helper T cell (T1)/classically activated macrophage M1 response, with detection of elevated interferon-γ, tumor necrosis factor-α, IL-12, and STAT1 levels in the muscle tissue, which may serve as biomarkers and aid in diagnostic decisions. Furthermore, B cells and high expression of the chemoattractant CXCL13 were identified in a subgroup of patients with defined autoantibodies. Taken together, we propose a diagnostic armamentarium that allows for clear differentiation between IMNM and nIMNM. In addition, we have characterized a Th1-driven, M1-mediated immune response in most of the autoimmune necrotizing myopathies, which may guide therapeutic options in the future.

IL-1α-dependent sterile inflammation in atherosclerosis is cell type-dependent and driven by necrotic vascular smooth muscle cells

IL-1α-dependent sterile inflammation in atherosclerosis is cell type-dependent and driven by necrotic vascular smooth muscle cells

Is a Muscle Biopsy Necessary for the Diagnosis of Inclusion Body Myositis (IBM)? (P07.223)

Objective: To determine if a muscle biopsy is superior or adds to the clinical diagnosis of inclusion body myositis. Background Inclusion body myositis is a mixed degenerative and inflammatory disease. There is no effective treatment. The diagnosis is confirmed by muscle biopsy showing congophilic deposits and rimmed vacuoles or by electronmicroscope showing the filamentous inclusions. Design/Methods: Twenty-one patients with clinical diagnosis of inclusion body myositis underwent muscle biopsy for confirmation. All patients had proximal and distal muscle weakness with preferential involvement of finger flexors and quadriceps muscles. Muscle biopsies were performed from a moderate weak muscle and were examined for the presence of rimmed vacuoles or congophilic deposits or both. Results: There were fourteen females and seven males. Average age at presentation was 60 years (35-80). CK level was elevated in 18 patients. Mean CK elevation was 942 U/L and ranged from 72-4774. Mean disease duration before the biopsy was 6 years and ranged from 1-15 years. The muscle biopsy confirmed the diagnosis in 15 patients. Six patients (5 females and 1 male) had no rimmed vacuoles or congophilic deposits detected on their muscle biopsies, but all patients had autoaggressive endomysial inflammatory response with mononuclear cells invading none necrotic muscle fibers. Ten patients had received different types of immunotherapy, but continued to deteriorate. Conclusions: 1- None of the patients suspecting to have IBM was found to have a different diagnosis.2- The muscle biopsy did not show the characteristic features of IBM in six patients.3- These findings question whether or not the muscle biopsy is necessary or add to the clinical diagnosis of inclusion body myositis.4-The clinical diagnosis of IBM remains superior to the muscle biopsy. Disclosure: Dr. Lee has nothing to disclose. Dr. Chahin has nothing to disclose.

Clinical and Pathological Features of Childhood-Onset Nemaline Myopathy: A Report of Four Cases

We examined whether immunological abnormalities can be found in the specimens of four childhood-onset nemaline myopathy (NM) patients without autoimmune diseases. Pathological examination revealed that nemaline rods were found in all specimens. The immunohistochemical results showed that CD4 positive cells and some other cells were gathered among the necrotic muscle fibers. We conclude that immunological abnormalities are present in the specimens of certain childhood-onset NM patients without autoimmune diseases. Further evaluation of the immunological changes is warranted in childhood-onset NM patients.

Distal myopathy with rimmed vacuoles: clinical and muscle morphological characteristics and spectrum of GNE gene mutations in 53 Chinese patients

Objectives: Distal myopathy with rimmed vacuoles (DMRV) is a typical autosomal recessive hereditary inclusion body myopathy, characterized by slowly progressive distal muscle weakness with relative sparing of the quadriceps. This study aimed to investigate the variability of clinical and morphological presentation and the spectrum of Glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase (GNE) mutations in Chinese DMRV patients.Methods: We retrospectively reviewed the medical records of 37 patients with DMRV in PLA General Hospital from 1986 to 2011, and further conducted a review of 16 reported Chinese DMRV patients from other hospitals. We systematically analyzed the clinical, muscle morphological features and GNE gene mutation status of all DMRV patients.Results: A total of 53 DMRV patients were studied. Fourteen cases had family history and other 39 cases were sporadic. Fifteen cases showed atypical pathological presentation as mononuclear cell invasion into necrotic or non-necrotic muscle fibers. Rare initial symptom, earlier age of onset and more dysmorphic presentations were shown in sporadic patients. Eighteen mutations in GNE gene were identified. c.317T>C (p.I106T) was a novel GNE gene mutation. c.1892C>T (p.A631V), c.527A>T (p.D176V) and c.1523T>C (p.L508S) were the common GNE mutations in Chinese DMRV patients.Discussion: The clinical, pathological and genetic characteristics of DMRV are distinct in Chinese patients.