Patients Underwent Muscle Biopsy Research Articles

Patient experiences of muscle biopsy in idiopathic inflammatory myopathies: a cross-sectional survey

Introduction: Muscle biopsy plays an important role in the diagnostic evaluation of individuals with suspected idiopathic inflammatory myopathies (IIM). However, variability in biopsy practices may result in a heterogenous patient experience. The existing literature offers limited insights into the experiences and perspectives of patients undergoing muscle biopsy. Methods: This study employed a 27-item online survey to comprehensively characterise the experience of muscle biopsy among Australian patients, including their concerns, beliefs about procedure utility, information sources, physical sensations, perceived complications and recovery. Results: A total of 111 Australian individuals who reported a diagnosis of IIM completed the survey, with data collected from March to June 2023. Most participants had inclusion body myositis (76/111, 68.5%) and had undergone one biopsy procedure (87/111, 78.4%) as part of their IIM work-up. Nine of the 111 respondents did not undergo a muscle biopsy. The procedure was well-tolerated by many respondents, however, a notable number of respondents experienced post-procedural pain lasting > 72 h (27/102, 26.5%), increasing weakness post-biopsy (13.7%), numbness at the biopsy site (18/102, 17.6%) and a recovery time beyond 3 days (36/102, 35.3%). A substantial minority (30/111, 27%) felt they were inadequately informed about the risks and benefits of the procedure. Conclusions: This survey highlights that although muscle biopsy is often well-tolerated, there are considerable patient concerns that are often inadequately addressed. Our findings underscore the need for improved patient-doctor communication and support throughout the biopsy process.

Magnetic resonance imaging patterns revealing muscle pathology and clinical features in idiopathic inflammatory myopathies.

Idiopathic inflammatory myopathies (IIMs) are autoimmune disorders significantly impacting skeletal muscles; however, the precise correlation between muscle magnetic resonance imaging (MRI) findings, muscle pathology, disease subtypes and clinical characteristics remains uncertain. Thus, we investigated the association of muscle MRI findings in IIMs with muscle pathology and clinical features. New-onset IIM patients underwent proximal upper and/or lower limb muscle MRI. Patterns of muscle oedema on MRI were categorised into fascial, honeycomb, peripheral, foggy, dense, or coarse dot patterns and compared with inflammatory cell infiltration sites in corresponding muscle biopsies. The incidence of MRI patterns was examined in patient subgroups using myositis-specific antibodies (MSAs) and 2017 EULAR/ACR classification criteria. Univariate and multivariate analyses were conducted to determine the odds ratios (ORs) of MRI findings for clinical characteristics. Fifty-six of 85 patients underwent muscle biopsy. Foggy, honeycomb and fascial patterns at biopsy sites correlated with inflammatory cell infiltration in the endomysium (OR 11.9, P = 0.005), perimysium (OR 6.0, P = 0.014) and fascia (OR 16.9, P < 0.001), respectively. Honeycomb and foggy patterns were characteristic of patients with anti-TIF1γ or anti-Mi2 antibodies and MSA-negative dermatomyositis, and those with anti-SRP or anti-HMGCR antibodies and MSA-negative polymyositis (PM), respectively. The honeycomb pattern positively correlated with malignancy (OR 6.87, P < 0.001) and Gottron sign (OR 8.05, P = 0.002); the foggy pattern correlated with muscle weakness (OR 11.24, P = 0.005). The dense dot pattern was associated with dysphagia (OR 6.27, P = 0.006) and malignancy (OR 8.49, P = 0.002). Muscle MRI holds promise in predicting muscle pathology, disease subtypes and clinical manifestations of IIMs.

Effects of Remimazolam on Intracellular Calcium Dynamics in Myotubes Derived from Patients with Malignant Hyperthermia and Functional Analysis of Type 1 Ryanodine Receptor Gene Variants.

Remimazolam is a novel general anesthetic and its safety in patients with malignant hyperthermia (MH) is unknown. We used myotubes derived from the skeletal muscle of patients with MH to examine the response to ryanodine receptor 1 (RYR1) agonist and remimazolam in MH-susceptible patients. Patients underwent muscle biopsy for the Ca2+-induced Ca2+ release (CICR) rate test, a diagnostic tool for MH in Japan. Ten patients had myotubes obtained from skeletal muscle cultures, and the genes associated with malignant hyperthermia in these patients were analyzed. The EC50 of caffeine, cresol, and remimazolam to induce intracellular calcium concentration change were compared between myotubes from CICR-negative genetic test patients and myotubes from other patients. Eight of the ten were CICR-positive, five of whom had RYR1 causative gene mutations or variants. Two patients had CICR-negative genetic tests, and as expected had the highest EC50 (the concentration of a drug that gives a half-maximal response) in response to caffeine, 4CmC and remimazolam. Three patients had a positive CICR but no known variants in RYR1 or CACNA1S (voltage-gated calcium channel subunit alpha1S). Myotubes in these patients had significantly lower EC50s for all agents than myotubes in CICR-negative patients. When myotubes from a patient who was CICR-negative and had no gene variant were used as a control, myotubes from CICR-positive patients were more hyper-responsive than controls to all stimulants used. The EC50 for remimazolam was lowest for myotubes from CICR-positive, RYR1-mutant patients, at 206 µM (corresponding to 123 µg/mL). The concentration was more than 80-times higher than the clinical concentration. RYR1 gene variants in R4645Q and W5020G were shown to be causative gene mutations for MH. Intracellular calcium in myotubes from MH patients are elevated at high concentrations of remimazolam but not at clinically used concentrations of remimazolam. Remimazolam appears to be safe to use in patients with MH.

Characteristics of cardiac involvement in immune-mediated necrotizing myopathy.

To investigate the characteristics of cardiac involvement due to Immune-mediated Necrotizing Myopathy (IMNM). Patients diagnosed with Immune-mediated Necrotizing Myopathy (IMNM) who attended the Department of Neurology and the Department of Rheumatology and Immunology at the First Medical Center of the PLA General Hospital between February 2011 and June 2022 were collected. Clinicopathological diagnosis of IMNM was performed according to the criteria established by the European Neuromuscular Center (ENMC). All patients underwent muscle biopsy and Myositis-specific antibodies (MSAs) testing. Information included age, gender, disease duration, intramuscular and extramuscular manifestations, laboratory findings (including creatine kinase, lactate dehydrogenase levels, troponin T, myoglobin and atrial natriuretic peptide), electromyography, skeletal muscle pathology and immunohistochemical staining. A total of 57 patients were included in this study. Of the serological tests, 56.1% (32/57) were positive for SRP, 21.1% (12/57) were positive for HMGCR and 22.8% (13/57) were seronegative. Thirty patients (52.6%, 30/57) presented with varying degrees of cardiac involvement. We performed ECG in 23 patients and found 6 patients with arrhythmia (26.1%), 12 patients with myocardial ischemia (52.2%), and 7 patients with acute coronary syndrome (ST elevation and non-ST elevation myocardial infarction) (30.4%), and 4 patients with left axis deviation or left ventricular high voltage, suggesting left ventricular hypertrophy (17.4%). Cardiac ultrasound was performed in 14 patients and 3 showed pericardial effusion (21.4%); Decreased left ventricular ejection fraction and atrial enlargement were 2 each; 8 showed a decrease in left ventricular diastolic function (57.1%). In addition, one patient had myocardial edema. Cardiac involvement is not uncommon in IMNM. However, besides clearly statistically significant differences in the disease course, and in the values of troponin T and myoglobin, our data did not show any statistically significant difference in other features of cardiac involvement between patients with different subtypes of IMNM.

Untargeted metabolomics profiling of skeletal muscle samples from malignant hyperthermia susceptible patients.

Malignant hyperthermia (MH) is a potentially fatal hypermetabolic condition triggered by certain anesthetics and caused by defective calcium homeostasis in skeletal muscle cells. Recent evidence has revealed impairment of various biochemical pathways in MH-susceptible patients in the absence of anesthetics. We hypothesized that clinical differences between MH-susceptible and control individuals are reflected in measurable differences in myoplasmic metabolites. We performed metabolomic profiling of skeletal muscle samples from MH-negative (control) individuals and MH-susceptible patients undergoing muscle biopsy for diagnosis of MH susceptibility. Cellular metabolites were extracted from 33 fresh and 87 frozen human muscle samples using solid phase microextraction and Metabolon® untargeted biochemical profiling platforms, respectively. Ultra-performance liquid chromatography-high resolution mass spectrometry was used for metabolite identification and validation, followed by analysis of differences in metabolites between the MH-susceptible and MH-negative groups. Significant fold-change differences between the MH-susceptible and control groups in metabolites from various pathways were found (P value range: 0.009 to < 0.001). These included accumulation of long chain acylcarnitines, diacylglycerols, phosphoenolpyruvate, histidine pathway metabolites, lysophosphatidylcholine, oxidative stress markers, and phosphoinositols, as well as decreased levels of monoacylglycerols. The results from both analytical platforms were in agreement. This metabolomics study indicates a shift from utilization of carbohydrates towards lipids for energy production in MH-susceptible individuals. This shift may result in inefficiency of beta-oxidation, and increased muscle protein turnover, oxidative stress, and/or lysophosphatidylcholine levels.

Duchenne muscular dystrophy: A immunohistochemical profile and deletion pattern in dystrophin gene in North Indian population

Background: Duchenne muscular dystrophy (DMD), one of the most common X linked muscular disorder, affecting 1 in 3500 male births and is caused by mutation in dystrophin gene. 65% of DMD cases are caused by large deletion of dystrophin gene, followed by duplication (5-10%) or point mutation (25-30%). There is wide mutation spectrum of the mutations in dystrophin gene. Hence, population specific information is needed on mutation spectrum and frequency of common mutations occurring in that particular population for appropriate counseling, prenatal diagnosis and for developing genetic therapy in future. Aims and Objectives: To find out the frequency and distribution of deletion in dystrophin gene in DMD patients along with contribution of pathology and genetic testing in diagnosis of DMD and Becker muscular dystrophy (BMD) in North Indian population.Materials and Methods: Dystrophin gene was screened for deletion by multiplex polymerase chain reaction (PCR). Out of 41 patients, 09 patients underwent muscle biopsy, on which immunohistochemistry was performed for dystrophin, sarcoglycan, dysferlin and merosin.Results: Majority of the deletions were located in distal hotspot region (26/39 ~66.66%) which includes the exons 45-55 and 15.38% of deletions were located at the proximal hotspot region (2- 19 exons).Conclusion: In the present study, 34% patients only showed deletion. Hence complete work up of any muscular dystrophy requires immnohistochemical analysis to see the expression of muscle proteins along with multipleplex PCR test to detect any exon deletion, multiplex ligation-dependent probe amplification (MLPA) to detect point mutation and duplication and western blotting to quantify the dystrophin protein.Asian Journal of Medical Sciences Vol.8(6) 2017 13-18

Serum Creatinine Distinguishes Duchenne Muscular Dystrophy from Becker Muscular Dystrophy in Patients Aged ≤3 Years: A Retrospective Study.

Here, we investigated correlations between serum creatinine (SCRN) levels and clinical phenotypes of dystrophinopathy in young patients. Sixty-eight patients with dystrophinopathy at the Neuromuscular Clinic, The First Affiliated Hospital, Sun Yat-sen University, were selected for this study. The diagnosis of dystrophinopathy was based on clinical manifestation, biochemical changes, and molecular analysis. Some patients underwent muscle biopsies; SCRN levels were tested when patients were ≤3 years old, and reading frame changes were analyzed. Each patient was followed up, and motor function and clinical phenotype were assessed when the same patients were ≥4 years old. Our findings indicated that in young patients, lower SCRN levels were associated with increased disease severity (p < 0.01) and that SCRN levels were the highest in patients exhibiting mild Becker muscular dystrophy (BMD) (p < 0.001) and the lowest in patients with Duchenne muscular dystrophy (DMD) (p < 0.01) and were significantly higher in patients carrying in-frame mutations than in patients carrying out-of-frame mutations (p < 0.001). SCRN level cutoff values for identifying mild BMD [18 µmol/L; area under the curve (AUC): 0.947; p < 0.001] and DMD (17 µmol/L; AUC: 0.837; p < 0.001) were established. These results suggest that SCRN might be a valuable biomarker for distinguishing DMD from BMD in patients aged ≤3 years and could assist in the selection of appropriate treatment strategies.

Selective or predominant triceps muscle weakness in African–American patients with myasthenia gravis

Myasthenia gravis (MG) can lead to weakness in different patterns of muscle groups. Limb muscle weakness is most typically seen in a limb girdle pattern, although variants exist. In the current study, we aimed to describe a unique MG phenotype consisting of selective or predominant triceps muscle weakness. We performed a retrospective review of MG patients who developed focal or predominant triceps muscle weakness between 2006 and 2016. The clinical, electrophysiological and serological characteristics of these patients were examined. 8 MG patients were identified, including 7 males, all of whom were African–American. Two patients underwent muscle biopsy, and one patient underwent cervical spine decompression surgery. All showed significant improvement following immunosuppressive treatment, although one patient experienced a relapse of muscle weakness. This case series highlights a relatively uncommon MG clinical phenotype of selective triceps muscle weakness, mainly in African–American males, in line with previous literature. Familiarity with this phenotype is important in order to facilitate diagnosis and appropriate treatment for this group, and avoid unnecessary investigations or treatments.

Diagnosis and Management of Kearns-Sayre Syndrome Rely on Comprehensive Clinical Evaluation

We appreciate the readers’ interest and their comprehensive comments and advice about the article,[1] which mainly concerned details of the patients’ information. In this paper, we reported 19 Kearns-Sayre syndrome (KSS) patients whose diagnoses were in accordance with the current clinical diagnostic criteria of KSS, i.e., the triad of progressive external ophthalmoplegia, pigmentary retinopathy, and onset before 20 years of age, plus at least one of the followings: heart block, cerebellar symptoms, or cerebrospinal fluid protein levels above 1000 mg/L.[2] The diagnostic criteria have been widely used.[3] Apart from clinical features, muscle pathology and molecular genetic analysis can play a great role in the diagnostic workup. Muscle pathology showed ragged-red fibers (RRF), ragged-blue fibers (RBF), or cytochrome c-oxidase (COX)-negative fibers in almost all patients.[4] Southern blot or long-range polymerase chain reaction can detect single large-scale deletion in about 90% of KSS patients,[5] while mitochondrial DNA (mtDNA) point mutations or nuclear gene mutations have been reported in other KSS patients.[6] In general, single large-scale deletion can be detected only from the muscle, but not from blood cells of KSS patients.[7] Among the 19 patients reported by us, 15 patients underwent muscle biopsy in our hospital which showed RRF, RBF, and COX-negative fibers in all of them; however, mtDNA mutation detection was available in 11 of them because muscle tissue of the other four (patients 8, 10, 17, and 18) were not enough for further gene analyses; one patient (patient 12) had muscle biopsy in another hospital, and we got a little muscle tissue to do the mutation examination although RBF% cannot be counted. Three patients (patients 2, 5, and 7) refused to receive muscle biopsy, but all of them showed typical KSS features. We performed common mtDNA point mutations analysis (mtDNA A3243G, A8344G) in their blood, which were negative. Biochemical investigations, especially activity assay of respiratory chain complexes in muscle tissues, can also help provide evidence for the diagnosis of mitochondrial disease.[8] Unfortunately, such a detecting platform has not been established in our laboratory. There were several articles studying the exact nature of high signal lesions on diffusion-weighted imaging (DWI) in patients with mitochondrial diseases, especially mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. However, the results were conflicting since some reported an increase in the apparent diffusion coefficient (ADC) values suggesting vasogenic edema while others described a decrease in the ADC values reflecting cytotoxic edema.[9] In our KSS patients, we also found the same interesting phenomena that the ADC values of the regions with high signal on DWI were not consistent. Some patients showed increased ADC values while the others showed decreased ADC values. We proposed that the discrepancy might be due to the different disease stages in different individual patients although further studies are needed to elucidate the underlying pathophysiological mechanism. The results of Moraes et al.[2] showed cognitive decline in 31% of KSS patients, which was associated with the presence of disability. In our research, the present study was mainly focused on the electrocardiogram and brain magnetic resonance imaging changes of the patients. Cognitive function was only evaluated in one patient, which also showed a moderate decline of cognitive function. In our research, all the patients underwent Holter monitoring, and as we reported in the article, none of them developed ventricular arrhythmias, which was also a big difference from previous reports. Therefore, the cardiologists did not suggest implantable cardioverter defibrillator implantation in these patients. According to the height and weight standardized growth charts for Chinese children and adolescents aged 0–18 years,[10] we only found the heights of three patients more than two standard deviations below the mean for age and gender. The heights of other six patients were below the mean height for age and gender but did not reach the definition for short stature. Again, we show our greatest thanks for the comments and advices, and hope that we can learn more about the disease to bring more effective treatment for the patients in the near future, by our efforts together.

Role of magnetic resonance imaging in the diagnosis of juvenile dermato-myositis and polymyositis in Chinese children

Objective: To evaluate the utility of magnetic resonance imaging (MRI) in diagnosis of juvenile dermatomyositis and polymyositis (JDM-PM) in children. Method: Fifty-four patients with JDM-PM in the active stage were enrolled in the study group. Twelve patients with benign acute childhood myositis and forty patients with juvenile idiopathic arthritis (JIA) complicated with myositis were enrolled as controls. MRI imaging of thighs was performed in all patients, fast spin echo T1WI, T2WI, and STIR were obtained in all patients.Muscle biopsy was performed in 41/54 patients with JDM-PM. We compared the value of MRI in diagnosis of JDM-PM with muscle biopsy, electromyography and serum aspartate transaminase (AST), alanine transaminase (ALT), creatine kinase (CK), isoenzyme of creatine kinase (CKMB), lactate dehydrogenase (LDH), hydroxybutyrate dehydrogenase (HBDH) levels. Continuous normally distributed variables were reported as means and continuous non-normally distributed variables as median. Chi-square test and Fisher exact test were used to test differences between MRI and other categorical variables. Result: A total of 54 patients were included. Twenty-seven patients were male and the others were female. Average age of the patients was (7.1±3.5) years (2-13 years); 45(83%) paitests were JDM cases and 9(17%) patients had JPM. All patients had MRI examination. Of the 54 patients, 53 had multiple myositis; 10 out of 50 (19%) patients received second MRI after treatment, 6 out of 10 patients had normal findings, 4 patients showed obviously improved images; 41 out of 54 patients underwent muscle biopsy; 22 out of 41 patients had inflammatory cells infiltration and muscle fiber degeneration. The results of the muscle enzyme tests are as follows: 27 (50%) patients had elevated AST, 24 (44%) patients had elevated ALT, 22 (41%) patients had elevated CK, 18(33%) patients had elevated CKMB, and LDH rose in 30 (56%) patients, HBDH rose in 28(52%) patients. These results suggested that muscle MRI was more sensitive than muscle biopsy and muscle enzyme tests in diagnosis of JDM-PM. Conclusion: Patients with JDM-PM showed diffuse patchy hyperintense signals on T2WI of their thighs. MRI may be a sensitive, reliable, and noninvasive tool for clinical diagnosis and theraputic evaluation of JDM-PM.

Anesthetic management of 877 pediatric patients undergoing muscle biopsy for neuromuscular disorders: a 20‐year review

The objectives are to review the anesthetic management and anesthetic-related adverse events in patients undergoing muscle biopsy for a broad spectrum of neuromuscular disorders (NMD). The study aims to assess the hypothesis that perceived awareness of potential anesthesia-induced hyperkalemia and MH in patients with NMD reduces the frequency of such events. A 20-year retrospective review of 877 consecutive patients undergoing muscle biopsy to establish diagnoses of NMD has been performed. Patients were categorized prebiopsy into six groups: M (myopathy and muscular dystrophy), MM (mitochondrial or metabolic myopathy), N (neurodegenerative, peripheral neuropathy or spinal muscular atrophy disorder), D (dermatomyositis), C (cardiomyopathy), or S (seizure disorder). Data were collected for demographics, anesthetic management, pre- and postoperative anesthesia-induced muscle injury, postbiopsy histopathologic diagnosis, and concordance comparisons between pre- and postbiopsy diagnoses. There were 513 males (58.5%) and 364 females (41.5%) (1.4:1) with 137 individuals (15.6%) operated on under 1year of age and two-thirds by 6years of age. NMD diagnosis was reached in 409 (46.6%) while 468 (53.4%) had no specific pathology. No patients exhibited signs of anesthesia-induced muscle injury (malignant hyperthermia, rhabdomyolysis, cardiac arrest, or postoperative deterioration of weakness). MM was the largest group pre biopsy (367, 41.8%). Anesthetic agents were: nitrous oxide in 657 (74.9%); volatile agents in 139 (15.8%); intravenous agents in 836 (95.3%) (primarily propofol, midazolam, and fentanyl); nondepolarizing muscle relaxants in 404 (46.1%); and regional anesthesia in 112 (12.8%) [most commonly spinal anesthesia in 80 (71.4%)]. Comparing preoperative diagnostic category with postoperative diagnosis, there was a concordance of 78% (319/409) between the two for cases with a definitive diagnosis and 89.7% (787/877) for all cases. In this retrospective study, no patient exhibited signs or symptoms of hyperkalemia or MH probably because the incidence is very low and becomes even less likely due to the selection of the various anesthetic agents and strategies administered.

Clinical, pathological and genetic characteristics of autosomal dominant inherited dynamin2 centronuclear myopathy.

The aim of the present study was to report on a family with pathologically and genetically diagnosed autosomal dominant inherited centronuclear myopathy (CNM). In addition, this study aimed to investigate the clinical, pathological and molecular genetic characteristics of the disease. This pedigree was traced back three generations, four patients underwent neurological examination, two patients underwent muscle biopsy, and eight family members were subjected to dynamin2 (DNM2) gene mutation analysis. DNM2 mutations were detected in seven family members, of which four patients exhibited DNM2 mutation‑specific clinical and pathological features. Lower extremity weakness was the predominant symptom of these patients, however, proximal and distal lower extremity involvement was inconsistent. All patients exhibited marked systematic muscle atrophy and various degrees of facial muscle involvement. The patients presented the typical pathological changes of CNM, and their muscle tissues were heavily replaced by adipose tissue, with clustered distribution of muscle fibers as another notable feature. DNM2‑CNM patients of this pedigree exhibited heterogeneous clinical and pathological features, providing a basis for further molecular genetic analysis.

The use of muscle biopsy in the diagnosis of systemic vasculitis affecting small to medium-sized vessels: a prospective evaluation in Japan

Objectives: The aim of this study was to assess the use of muscle biopsy for histopathological confirmation of small vessel vasculitis (SVV) or medium vessel vasculitis (MVV).Method: Muscle biopsies were performed for all consecutive cases of suspected SVV or MVV seen at Tokyo Metropolitan Tama Medical Centre between February 2012 and May 2014 except those for which a skin or renal biopsy was indicated.Results: Forty-nine patients underwent muscle biopsies. All patients were followed for a minimum of 6 months. Diagnosis of SVV or MVV was made in 35 patients. An unrelated condition was diagnosed in 11 patients and no diagnoses were made in three patients. Of the 35 patients in whom SVV or MVV was diagnosed, positive muscle biopsies were obtained in 20 patients [15 microscopic polyangiitis (MPA), three polyarteritis nodosa (PAN), and two eosinophilic granulomatosis with polyangiitis (EGPA)], while other findings led to the same diagnosis in 15 (seven MPA, four GPA, three PAN, and one rheumatoid vasculitis). The sensitivity of the muscle biopsy was 57% [20/35; 95% confidence interval (CI) 50–57]. Of 13 patients presenting with peripheral neuropathy, the muscle biopsy demonstrated vasculitis in nine patients, with 75% sensitivity (9/12; 95% CI 69–75). There were no complications in the procedure apart from delayed wound healing in one patient.Conclusions: Muscle biopsy is a safe method that offers a high diagnostic yield for SVV or MVV, especially in patients with vasculitic neuropathy.

SLE myopathy: a clinicopathological study.

To study the histological changes in muscle biopsy in patients diagnosed with systemic lupus erythematosus (SLE) and presenting with muscle symptoms. Patients with SLE presenting with muscle symptoms at presentation or during follow-up and treatment between January 2010 and May 2014 and who underwent muscle biopsy were included in the study. Demographic, clinical features, serological markers, and Electromyoneurography findings were collected. Muscle biopsies were evaluated for inflammation, fiber type abnormalities, vasculitis and interstitial changes according to 2004 European Neuromuscular Centre criteria. Fifteen patients underwent muscle biopsy in the study period. Clinical presentations included mucocutaneous (9), musculoskeletal (14), hematological (3), renal (8), hepatic (1) and central nervous system (CNS) (4) manifestations, and neuropathy (4), serositis (2), Raynaud's phenomenon (1) and infectious complications (8). Histological findings were perivascular/perimysial inflammation (7/15), type 1 predominance (7/15) and type 2 atrophy (13/15). Clinical evidence of myositis was seen in 8.8% of patients in the SLE registry, whereas histological evidence of myositis was seen in 46.66% of biopsied patients with muscle symptoms. There was no significant difference in clinical, serological, laboratory and muscle histology features between groups of patients with or without myositis. Type 2 atrophy was the predominant finding in SLE patients irrespective of time of muscle biopsy, treatment received and presence or absence of myositis. Histological evidence of myositis was found in 46.66% of SLE patients and there were no significant differences in clinical/laboratory features in patients with or without myositis. Type 2 atrophy was seen in patients irrespective of time of the biopsy, treatment received and presence or absence of myositis. Type 2 atrophy was considered the major cause for muscle symptoms.

G.P.49: RYR1 mutations in adults with acute rhabdomyolysis episodes

Recurrent rhabdomyolysis episodes in adults are commonly caused by glycogenosis or fatty-acid oxidation disorders. However, in many cases the etiology remains unknown, and recently mutations in RYR1 appeared as a possible cause of exercise induced rhabdomyolysis. We studied 14 adults who presented acute rhabdomyolysis (CK above 10,000 UI/l) triggered by exercise or fever, in whom McArdle disease, fatty acid oxidation disorders, and LPIN1 mutations were excluded. All patients underwent muscle biopsy in order to screen RYR1 mutation on cDNA. Potentially pathogenic mutations in RYR1 gene were detected in 5 unrelated patients. Mutations were the following: p.Val4847Leu, p.G593R, p R3539H, Gly2434Arg, p.Gln3461Pro, p.A1352T, p.A933T and p.Ser1342Gly. Two patients presented each 2 and 3 heterozygous variants. Baseline CK levels were elevated in all cases but one (400–700 UI/l). None of them complained of myalgia or exercise intolerance. Rhabdomyolysis were triggered by weight-training in two patients, viral infection in two cases, and retinoic acid treatment in the last case. Higher recorded CK levels were between 28,000 and 94,000 UI/l, without renal failure. Three patients had a unique episode, whereas two other had several rhabdomyolysis episodes. Muscle biopsies were either normal, or showed moderate structure disorganization. Two siblings of a patient, the father of another patient, and the brother of a third patient, also presented mutations in the RYR1 gene and high baseline CK level. Per-anesthetic malignant hyperthermia was noticed in a grand-mother of one patient. Mutations in RYR1 gene should be systematically searched in patients with exercise or fever induced rhabdomyolysis episodes, after having excluded common metabolic disorders. This diagnostic implies major consequences for genetic counselling in the families, due to the potential risk of anesthetic malignant for the patients and their relatives.

G.P.42: Mild clinical phenotype in two siblings carrying myotubular myopathy

Among congenital myopathies, X-linked recessive myotubular myopathy is one of the most severe forms. The majority of patients present with severe hypotonia at birth and respiratory insufficiency and most of them die in the first year of life. However, there is phenotypic variability. Here, we report two patients carrying a missense mutation in MTM1 gene and presenting with a mild phenotype. The first boy was born on time with respiratory insufficiency and generalised hypotonia. He required ventilator support for 3 weeks, and then he went home without specific care. He walked at 11 month. He is now 24 and can run, practices canoe and works as a salesperson. At the exam, he presents mild proximal weakness and restrictive syndrome with no ventilator support (VC = 57%). His brother was born on time with respiratory insufficiency and hypotonia. He stayed in intensive care unit for 6 weeks, then went home without support. He walked at 18 months. Respiratory involvement was more severe than his brother with a severe restrictive syndrome (VC = 33%) but the young man refused non-invasive night-time ventilation proposed at the age of 16. Being now 20, he can walk without any difficulty but cannot run. Clinical exam reveals a mild proximal weakness. Both patients underwent muscle biopsy showing the typical centronuclear myopathy pattern. Molecular analysis of MTM1gene found a hemizygous mutation c.575A>G in exon 8 leading to a missense p.Tyr192Cys. A decreased level of the MTM1 protein was observed by western blot analysis on lymphoblasts. To date, about 300 different mutations in around 540 families have been identified in MTM1 gene, including point mutations, insertions and small and large deletions and duplication. Around 70% of patients presenting with a mild or moderate phenotype carries a missense mutation, which is also the most frequent type of mutation. Another patient has been described with the same mutation (c.575A>G) and presented also with a mild phenotype.

Skeletal Muscle Microvasculature in the Diagnosis of Neuromuscular Disease

Blood vessels are often overlooked in analyses of skeletal muscle biopsies. However, there are many vascular features in skeletal muscle biopsies that, when interpreted in the context of other histologic patterns and clinical history, provide useful information that allows muscle pathologists to narrow their differential diagnoses and provide more accurate guidance to treating physicians. Here, we provide a review of normal skeletal muscle vasculature with details of the ultrastructure of vessel walls. We discuss the vascular effects of factors common to many patients undergoing muscle biopsy, for example, diabetes mellitus, hypertension, and aging. We then discuss vascular findings relevant to diagnostic muscle biopsy evaluation, with current theories of pathogenesis and detailed descriptions of the important features.

Merosin deficient congenital muscular dystrophy: Clinical, neuroimaging and immunohistochemical study of 8 Egyptian pediatric patients

Congenital muscular dystrophies (CMD) are a group of heterogeneous inherited autosomal recessive disorders characterized by muscular weakness, hypotonia and contractures. The Merosin Negative CMD (MNCMD) is considered to be the most severe form and is usually associated with white matter abnormalities as seen with brain imaging. Merosin is also expressed in the nervous system and its deficiency could affect its development. This article describes the clinical picture, muscle biopsy findings and neuroimaging abnormalities of eight Egyptian Pediatric patients with the clinical presentation of merosin negative congenital muscular dystrophy. The leading clinical presentation in almost all patients was severe hypotonia, muscular weakness and failure to achieve motor developmental milestones, only Case 2 walked at 2 years of age. Mentality was normal in most patients with exception of Case 2 in whom scholastic achievement was poor and was associated with behavior abnormality. Serum Creatine kinase ranged from moderate to severe elevation, 536–3563 U/L, Electromyography demonstrated a myopathic pattern in all patients. Brain MRI showed extensive demyelination of the cerebral white matter in 6/8 patients with extension to cerebellar demyelination in Case 5. 5/8 patients underwent muscle biopsy for which immunofluorescence staining for merosin demonstrated complete deficiency of laminin α2 in Case 5 & partial deficiency of laminin α2 in Case 2. This report demonstrates the utility of Immunofluorescence staining as a guide to confirm the diagnosis of MDCMD especially when molecular diagnosis is not available.

Prognosis of Statin Myopathy (P04.090)

Objective: To characterize the prognosis of statin myopathy. Background Statin drugs cause myalgias, fatigue, weakness, and CK elevation, which often linger after discontinuing the drugs. The prognosis has not been well studied. Design/Methods: 143 patients with a diagnosis of toxic myopathy or myopathy and hyperlipidemia were identified from our patients9 database. 69/143 with muscle symptoms and/or CK elevation developed after initiating statin therapy without other identifiable causes were chosen for further studies by chart review. Results: Mean age at presentation was 62 years (range:37-91). 49 (71.0%) patients were men. Mean duration of statin use was 29.6 months (range:0.25-122). Myalgias was reported by 63 (91.3%), fatigue by 47 (68.1%), and weakness by 42 (60.9%). 18 (26.1%) patients had detectable muscle weakness. Mean CK level at presentation was 790 IU/L (range: 33-5091), normal in 17 (24.6%), mildly elevated ( 1,000) in 16 (23.2%). 32 (46.4%) patients had NCS/EMG, with myopathy diagnosed in 4 (12.5%). 16 (23.2%) patients underwent muscle biopsies, with non-specific myopathic changes seen in 4 (25.0%). Statin was discontinued in all patients. Mean duration of follow-up was 18.2 months (range: 1-120). Muscle symptoms completely resolved in 50 (72.5%), improved in 9 (13.0%), and unchanged in 10 (14.5%). Of those with symptoms resolved, 24.0% occurred within 1 month, 62.0% within 3 months, 90.0% within 6 months, and 96.0% within 1 year. 10/52 (19.2%) patients had their CK levels return to normal. Clinical improvement was not influenced by the presence of weakness, CK elevation, or myopathic changes on EMG or muscle biopsies. Conclusions: Majority of patients with statin myopathy are men and their disease is mild. Muscle symptoms can linger but rarely beyond 1 year. NCS/EMG and muscle biopsy, which can be useful to rule out other diseases, are not helpful to determine the prognosis. Disclosure: Dr. Armour has nothing to disclose. Dr. Zhou has nothing to disclose.

Clinical analysis of 20 cases of muscular tuberculosis

To explore the clinical manifestations of muscular tuberculosis (MT) and analyze its risk factors. Twenty MT patients were recruited from our department during 2000 - 2010. There were 9 males and 11 females with an average age of 43.5 years old. And their clinical manifestations were recorded and analyzed. All patients had local masses. And 19 patients had the involvement of single muscle and multiple muscles were involved in 1 patient. Gastrocnemius was affected in 9 patients. Nine patients had a previous history of tuberculosis or suffered concurrent tuberculosis of other body parts. Three patients with immune system disease received glucocorticoid therapy. And 11 patients underwent PPD (purified protein derivative) test and only 1 was strongly positive while 10 others were negative. MT was confirmed by pathological examinations in 20 cases. All patients underwent muscle biopsy and received effective chemotherapy. As a kind of systemic disease, MT is mainly characterized by painful or painless muscle mass. The patients with a history of tuberculosis, tuberculosis of other body parts and immune system disease are susceptible to MT. Diagnosis is mainly made through biopsy. And chemotherapy is effective.