Muscle Biopsy Results Research Articles

The relationship between scoliosis and upper extremity functions in patients with Duchenne muscular dystrophy.

Objectives The aim of this study was to investigate the relationship between scoliosis and upper extremity functions in patients with Duchenne muscular dystrophy (DMD). Patients and methods Between January 2018 and July 2018, a total of 55 patients (54 males, 1 female; mean age: 9.9±2.9 years; range, 6 to 15 years) who were diagnosed with DMD based on the clinical, laboratory, muscle biopsy and molecular analysis results were included in this cross-sectional study. Scoliosis was evaluated and Cobb angles were measured. Functional Ambulation Scale and Brooke and Vignos scale scores were recorded. The ABILHAND-Kids questionnaire and Nine-Hole Peg Test (9-HPT) were used to assess the upper extremity functions. Hand grip strengths were also evaluated. Results The median ABILHAND-Kids scores and the hand grip strength values of the patients without scoliosis were significantly higher compared to those with scoliosis (p=0.002 and p=0.004 for right hand and p=0.012 for left hand, respectively). There was no statistically significant difference in the 9-HPT scores between the patients with and without scoliosis (p>0.05). We found a negative, significant correlation between the Cobb angle and ABILHAND-Kids scores in patients with scoliosis (r=-0.503; p=0.017). Conclusion Our study results show a moderate relationship between scoliosis and upper extremity functions. Scoliosis may adversely affect upper extremity functions in patients with DMD.

Focal vasculitic myositis as a primary manifestation of Behçet's disease: a case series of 10 Korean patients in a locomotive medicine clinic.

Muscle involvement in Behçet's disease (BD) is rare, and several cases have been reported in the literature. Therefore, this study aimed to describe the clinical, laboratory and imaging findings in adult patients presenting with BD-associated myositis before the diagnosis of BD. We retrospectively screened patients who visited a locomotive medicine clinic presenting with myalgia, local swelling, or tenderness of extremities without an established diagnosis of BD. We enrolled patients whose pain in the extremities was proven to be suggestive of focal vasculitic myositis and who were eventually diagnosed as having BD at the initial visit or during follow-up. We thoroughly reviewed the clinical, histological and imaging findings and treatment outcomes in patients who presented with focal vasculitic myositis as the primary manifestation of BD. Ten adult patients with focal vasculitic myositis as the primary manifestation of BD were enrolled. The lower and upper extremities were affected in eight and two patients, respectively. The affected lower extremities were the calf (n = 6) and thigh muscles (n = 2). The common findings of MRI included high signal intensity of the affected muscles and intermuscular fascia on fat-suppressed images, suggestive of myofascitis and oedematous changes in the subcutaneous layer. The results of skin or muscle biopsy were suggestive of vasculitis. All the patients were pain-free at the short-term follow-up (1-3 weeks) after oral steroid therapy. Focal vasculitic myositis can be a primary manifestation of BD warranting medical attention. BD-associated myositis responds well to oral steroid therapy.

Antisynthetase syndrome-An underdiagnosed entity

Anti-synthetase syndrome is an autoimmune disease, characterized by aminoacyl transfer RNA synthetase antibodies with clinical features that can include interstitial lung disease, myositis, Raynaud’s phenomenon, and arthritis. There is a higher prevalence and increased severity of interstitial lung disease in patients with the anti-synthetase syndrome as compared to other inflammatory myopathies. Diagnosis is made by serological, radiographic, and muscle and/or lung biopsy results. Patients frequently require multi-modality immunosuppressive therapy to manage muscular and pulmonary manifestations of the disease. Careful attention is required to the adverse effects and complications of chronic immunosuppressive therapy, as well as to the disease complications which include progressive interstitial lung disease, pulmonary hypertension, and malignancy. Increased awareness of this syndrome will allow for early diagnosis and treatment improving outcomes in patients.

New insights into the treatment of myositis.

The myositis syndromes include polymyositis, dermatomyositis (DM), necrotizing myopathy, inclusion body myositis (IBM), antisynthetase syndrome and overlap syndromes with myositis. These syndromes mostly occur in middle-aged patients, while juvenile DM occurs in children and adolescents. Patients mostly show a subacute weakness and myalgia in the upper and lower limbs, the diagnosis is based upon these clinical findings in combination with muscle biopsy results and specific serum autoantibodies. In recent years, research achieved a better understanding about the molecular mechanism underlying the myositis syndromes, as well as disease progress and extramuscular organ manifestations, such as interstitial lung disease and association with neoplasias. Treatment mainly consists of glucocorticosteroids and immunosuppressants. IBM is usually refractory to treatments. This review provides an overview of the current standards of treatment and new treatment options like monoclonal antibodies and new molecular therapies and their first results from clinical trials.

Muscle Toxicity of Drugs: When Drugs Turn Physiology into Pathophysiology.

Drugs are prescribed to manage or prevent symptoms and diseases, but may sometimes cause unexpected toxicity to muscles. The symptomatology and clinical manifestations of the myotoxic reaction can vary significantly between drugs and between patients on the same drug. This poses a challenge on how to recognize and prevent the occurrence of drug-induced muscle toxicity. The key to appropriate management of myotoxicity is prompt recognition that symptoms of patients may be drug related and to be aware that inter-individual differences in susceptibility to drug-induced toxicity exist. The most prevalent and well-documented drug class with unintended myotoxicity are the statins, but even today new classes of drugs with unintended myotoxicity are being discovered. This review will start off by explaining the principles of drug-induced myotoxicity and the different terminologies used to distinguish between grades of toxicity. The main part of the review will focus on the most important pathogenic mechanisms by which drugs can cause muscle toxicity, which will be exemplified by drugs with high risk of muscle toxicity. This will be done by providing information on key clinical and laboratory aspects, muscle electromyography patterns and biopsy results, and pathological mechanism and management for a specific drug from each pathogenic classification. In addition, rather new classes of drugs with unintended myotoxicity will be highlighted. Furthermore, we will explain why it is so difficult to diagnose drug-induced myotoxicity, and which tests can be used as a diagnostic aid. Lastly, a brief description will be given of how to manage and treat drug-induced myotoxicity.

A patient with dysphagia and muscle weakness

BACKGROUND: There are five major types of inflammatory myopathies (IM), including dermatomyositis, polymyositis, immune-mediated necrotizing myopathy, antisynthetase syndromes, and inclusion body myositis. Grouped together, the incidence of IM is >4 cases/100,000 with a prevalence of 14-32/100,000. Type-specific IM diagnoses are based on the pattern of muscle weakness and the results of electromyographs, MRIs, muscle biopsies, and measurements of myositis-specific autoantibodies1. We report the case of an elderly man with an inflammatory myopathy whose presenting complaint was dysphagia. OBJECTIVE: To review the clinical and laboratory manifestations of inflammatory myopathy-associated dysphagia. CASE REPORT: The patient is an 81-year-old retired Navy aviator who presented with a chief complaint of difficulty in swallowing both solids and liquids of several months duration. The dysphagia was associated with bouts of coughing, the expectoration of white foamy sputum, increased production of saliva, a weight loss of 5 kg, generalized myalgias, and worsening fatigue and weakness. The patient had a past medical history of essential hypertension, hyperlipidemia, autoimmune thyroiditis, V617F JAK2 + essential thrombocytosis, white matter microangiopathy, and a small lacunar infarction of the right caudate nucleus. There was no family history of autoimmune disease. On neurological examination, testing of cranial nerves II-XII and sensation to light touch, pin, temperature, and vibration was normal. The shoulder and upper arm strength was diminished bilaterally without evident muscle tenderness, atrophy or fasciculations. The patient could not rise from the supine position without assistance nor keep his arms elevated above his head without fatiguing. The strength in his lower extremities was normal. Deep tendon reflexes were normal and plantar responses were flexor. He had a single Gottron’s nodule and a faint erythematous rash involving his scalp, back and forearms. His Myositis Disease Activity Assessment (MDAAT) is shown in Table 1. Table 1. Myositis Disease Activity Assessment Tool (MDAAT) Findings on laboratory assessment included a normochromic normocytic anemia, thrombocyth-emia, a positive FANA IgG titer of 1:1280, and elevated levels of creatinine phosphokinase (1,373 U/L), aldolase (25.8 U/L), and antibodies to Mi-2 alpha, Mi-2 beta, MDA-5 and NXP-2 antigens. Anti-doubled stranded DNA, anti-RNP, anti-SM, anti-Jo-1, anti-SRP, anti-TIF-1ƴ and anti-synthetase antibody titers were negative. A modified barium swallow revealed severe oropharyngeal dysfunction with aspiration. An electromyograph, a muscle biopsy, and a MRI of cervical spinal muscles were indicative of an inflammatory myopathy. DISCUSSION: Dysphagia as a result of weakness of the oropharyngeal, laryngeal and esophageal musculature has been reported to develop in 10% to 73% of patients with inflammatory myopathy (IM) at some time during the course of their disease, and is most frequently seen in those with inclusion body myositis or malignancy- associated dermatomyositis. In a Mayo Clinic review of 62 patients with IM-associated dysphagia, 42% had inclusion body myositis, 29% dermatomyositis, 15% polymyosi-tis, and 15% an overlap syndrome. Dysphagia as the presenting complaint was most common in patients with inclusion body myositis (42%) followed by polymyositis and the overlap syndrome (11% each). IM-associated dysphagia had a mortality rate of 31% – 64% with the highest incidence of death occurring in patients with percutaneous endoscopic gastrostomies, an indirect measure of the severity of dysphagia. Death was most commonly the result of recurrent aspiration2. In a study of 92 patients with adult-onset dermatomyositis, Mugii and associates found that dysphagia was most prevalent in elderly patients, in males, and in patients with internal malignancies and/or elevated anti-TIF-1ƴ antibody levels3. In keeping with this report, the presented case is an elderly man with clinical and immunological evidence supporting a diagnosis of dermatomyositis, including an erythematous rash, a Gottron’s sign, and anti-Mi-2, anti-MDA-5, and anti-NXP-2 antibodies – autoantibodies associated with myositis, a classic dermatomyositis rash, and possible malignancy (see Table 2). Table 2. Patient’s myositis-specific autoantibodies* Agents most commonly used and reported to be beneficial in treating IM-associated dysphagia include prednisone, azathioprine, methotrexate, intravenous immunoglobulin, hydroxychloroqui-ne, and mycophenolate mofetil. Interventional procedures include enteral feeding and cricopharyngeal myotomies and dilations2. Inclusion body myositis is often recalcitrant to immunosuppressive treatment and is more likely to require interventional measures4. Our patient’s dysphagia is improving on methotrex-ate and prednisone. It is important to note that myositis patients presenting with complaints of dysphagia and weakness may be misdiagnosed as having amyotrophic lateral sclerosis, a disease in which serum CPK levels may be elevated and bulbar onset is common.

Electromyography and muscle biopsy in paediatric neuromuscular disorders – Evaluation of current practice and literature review

The conduct and interpretation of electromyography in children is considered difficult and therefore often avoided. We assessed the diagnostic accuracy of the paediatric electromyography protocol used in our tertiary reference centre and compared it to muscle biopsy results and clinical diagnosis. Electromyography was performed in unsedated children with suspected neuromuscular diseases between January 2010 and September 2017 and was analysed quantitatively. Muscle pathology was classified into seven groups based on existing histopathology reports. The clinical diagnosis, including myopathic, neurogenic and non-neuromuscular categories was used as the gold standard. 171 children between the age of 12 days to 17.4 years were included in the analysis. 41 children (24%) were under the age of 2 years at the time of electromyography. 98 (57%) children were diagnosed with a myopathic disorder, 18 (11%) with a neurogenic disease and 55 (32%) as not having a primary neuromuscular disorder. In detecting myopathic disease, electromyography performed as well as muscle biopsy (sensitivity 87.8% for electromyography vs. 84.5% for muscle biopsy; specificity 75.7% vs. 86.4%). This also applied to children under the age of 2 years (sensitivity 81.8% vs. 86.4%). Quantitative analysis of a limited electromyography protocol performed in unsedated children is a very valuable diagnostic tool.

DUCHENNE MUSCULAR DYSTROPHY - GENETICS: P.213The DMD Italian network: reporting 2127 genetic diagnoses of referred dystrophinopathies, reflections and impact on care and personalized therapies

Dystrophinopathies are allelic diseases caused by mutations in the dystrophin gene. DMD (generally out-of-frame mutations) and BMD (generally in-frame mutations) are the more frequent phenotypes, but dilated cardiomyopathy and mild to asymptomatic phenotypes also occur. Exceptions to the frame rule are also known. Genetic diagnosis of dystrophinopathies is complex and genotyping is currently mandatory both for accurate care including prevention and for eligibility in clinical trials. The DMD Italian network is composed by 11 centers offering dystrophin genetic analysis. 2127 patients were referred and genotyped. Among these, DMD were 59% and BMD 41% revealing a very high number of BMD phenotypes. Among DMDs, 58% carried deletions, 11% duplications and 30% small mutations. BMDs show 78% of deletions, 9% of duplications and 13% of small mutations. Notably, the percentage of small mutations in DMD is higher than those reported; similarly BMDs do show a very high number of deletions, and small mutations are more frequent than duplications. Among small mutations, 45% (DMD) and 33% (BMD) are nonsense; the 62,8 % of out-of-frame deletions is eligible for single exon skipping (17,8% for exon 53 skipping, 17% for exon 51 skipping, 16,6 % for exon 45 skipping, and 11,4% for exon 44 skipping). Among all diagnosed DMDs/BMDs, 10,5% remained orphan of a causative mutation. In these case revising the clinical diagnosis (especially the muscle biopsy results) is necessary, although this might also imply that atypical mutations may occur in a remarkable number of DMD and third level of genetic diagnosis (CGH or RNA profile) are needed. This very large patient cohort allows considerations about DMD/BMD mutation detection, mutation types percentage with repercussion on care and new therapies.

Case Report: Clinically amyopathic dermatomyositis presenting acutely with isolated facial edema.

A 45-year-old Asian man presented with acute-onset periorbital and facial edema associated with pyrexia. Muscle weakness was absent. Initial laboratory investigations showed an inflammatory reaction, while screening for infections was negative. Serum muscle enzyme levels were normal. He was hospitalized and treated empirically with antibiotics and corticosteroids, pending the result of facial skin and muscle biopsy. He showed a good clinical and laboratory response but an attempt to discontinue corticosteroids led to a prompt relapse of facial edema and pyrexia, associated with rising laboratory indices of inflammation. Biopsy findings were typical of dermatomyositis. Reintroduction of corticosteroid treatment resulted in complete clinical and laboratory remission. Facial edema as the sole clinical manifestation of dermatomyositis is extremely rare. There have been no previous reports of isolated facial edema in the setting of acute, clinically amyopathic dermatomyositis in adults. A high level of suspicion is required to make the diagnosis in the absence of myopathy and the hallmark cutaneous manifestations of the disease (heliotrope rash, Gottron papules).

Case Report: Acute amyopathic dermatomyositis presenting with isolated facial edema.

A 45-year-old Asian man presented with acute-onset periorbital and facial edema associated with pyrexia. Muscle weakness was absent. Initial laboratory investigations showed an inflammatory reaction, while screening for infections was negative. Serum muscle enzyme levels were normal. He was hospitalized and treated empirically with antibiotics and corticosteroids, pending the result of facial skin and muscle biopsy. He showed a good clinical and laboratory response but an attempt to discontinue corticosteroids led to a prompt relapse of facial edema and pyrexia, associated with rising laboratory indices of inflammation. Biopsy findings were typical of dermatomyositis. Reintroduction of corticosteroid treatment resulted in complete clinical and laboratory remission. Facial edema as the sole clinical manifestation of dermatomyositis is extremely rare. There have been no previous reports of isolated facial edema in the setting of acute amyopathic dermatomyositis. A high level of suspicion is required to make the diagnosis in the absence of myopathy and the hallmark cutaneous manifestations of the disease (heliotrope rash, Gottron papules).

Impact of muscle biopsy on diagnosis and management of children with neuromuscular diseases: A 10-year retrospective critical review

BackgroundMuscle biopsy facilitates morphologic, biochemical, and ultrastructural analysis of muscle for the purpose of making definitive neuromuscular diagnosis. However, muscle biopsy is an expensive, invasive, time-consuming, and resource-dependent procedure. The need for general anesthesia in children also increases the risks associated with this procedure. The aim of this study was to investigate the benefits of muscle biopsies performed over a 10-year period, with a focus on indications, suspected and histopathologic diagnosis, and impact on diagnosis and management decisions. MethodsWe retrospectively reviewed results of muscle biopsies performed in children at our center during the 2004 to 2014 study period. Clinical presentations, biopsy complications, pathologic results, and changes in management decision were reviewed and analyzed. ResultsBiopsies from 92 patients were included. Mean age of patients was 7.1years, and 66.3% were male. There were no perioperative complications, and definitive diagnosis was made in 74 patients. Regardless of whether pathologic changes were found or not, information gained from muscle biopsy significantly impacted prognosis and subsequent genetic counseling. ConclusionsMuscle biopsy is a safe and useful diagnostic tool in children suspected of having neuromuscular diseases, especially in those with muscle diseases. Definitive pathologic diagnosis helps to optimize treatment, counseling, and surveillance. The type of study and level of evidenceStudy of diagnostic test: level 1.

Clinical Characteristics of Spinal Muscular Atrophy in Korea Confirmed by Genetic Analysis.

The objective of this study was to review the clinical characteristics of patients with spinal muscular atrophy and to emphasize the importance of performing genetic mutational analysis at initial patient assessment. This is a single center oriented, retrospective, and descriptive study conducted in Seoul, South Korea. Genetic mutational analysis to detect the deletion of exon 7 of the SMN1 gene on chromosome 5q13 was performed by multiplex ligation-dependent probe amplification. Clinical features, electrodiagnostic study results, muscle biopsy results, and laboratory test results were reviewed from patient medical records. Of all 28 patients (15 males and 13 females), all showed bilateral symmetric proximal dominant weakness. Among them, 3 patients were classified as type I, 14 patients as type II, and 11 patients as type III. Twenty-five patients had scoliosis and eight of these patients received surgical treatment for scoliosis with improvement in clinical outcomes. Ventilator support was used in 15 patients. In terms of the diagnostic process, 15 patients had completed an electrodiagnostic study and muscle biopsy before genetic testing, and six of these patients were initially misdiagnosed with myopathy. Owing to the similar clinical features of SMA and congenital myopathy, an electrodiagnostic study and muscle biopsy could create confusion in the correct diagnosis in some cases. Therefore, it is recommended that genetic mutation analysis should be conducted along with an electrodiagnostic study or muscle biopsy in the diagnostic process for spinal muscular atrophy.

The Diagnosis and Treatment of Antisynthetase Syndrome.

Anti-synthetase syndrome is an autoimmune condition, characterized by antibodies directed against an aminoacycl transfer RNA synthetase along with clinical features that can include interstitial lung disease, myositis, Raynaud's phenomenon, and arthritis. There is a higher prevalence and increased severity of interstitial lung disease in patients with anti-synthetase syndrome, as compared to dermatomyositis and polymyositis, inflammatory myopathies with which it may overlap phenotypically. Diagnosis is made by a multidisciplinary approach, synthesizing rheumatology and pulmonary evaluations, along with serologic, radiographic, and occasionally muscle and/or lung biopsy results. Patients with anti-synthetase syndrome often require multi-modality immunosuppressive therapy in order to control the muscle and/or pulmonary manifestations of their disease. The long-term care of these patients mandates careful attention to the adverse effects and complications of chronic immunosuppressive therapy, as well as disease-related sequelae that can include progressive interstitial lung disease necessitating lung transplantation, pulmonary hypertension, malignancy and decreased survival. It is hoped that greater awareness of the clinical features of this syndrome will allow for earlier diagnosis and appropriate treatment to improve outcomes in patients with anti-synthetase syndrome.

A rare form of limb girdle muscular dystrophy (type 2E) seen in an Iranian family detected by autozygosity mapping

Sarcoglycanopathies (SGPs) constitute a subgroup of autosomal recessive limb girdle muscular dystrophies (LGMDs) which are caused by mutations in sarcoglycan (SGs) genes. SG proteins form a core complex consisting of α, β, γ and δ sarcoglycans which are encoded by SGCA, SGCB, SGCG and SGCD genes, respectively. Genetic defect, in any of these SG proteins, results in instability of the whole complex. This effect can be helpful in interpreting muscle biopsy results. Autozygosity mapping is a gene mapping approach which can be applied in large consanguineous families for tracking the defective gene in most autosomal recessive disorders. In the present study, we used autozygosity mapping, to find the gene responsible for muscular dystrophy. Proband was a 10-year-old boy referred to our center for ruling out DMD (Duchenne muscular dystrophy). According to the pedigree and clinical reports, we assessed him for SGPs. Haplotyping, using the four short tandem repeat (STR) markers for each of the SG genes, showed that the phenotype may segregate with SGCB gene; and observing two crossing overs which occurred within the gene suggested that the mutation might be in the first two exons of SGCB gene. Mutation analysis showed a 26 bp duplication (10 bp before the initiation codon till 13 bp after the ATG start codon). This will cause a frameshift in protein synthesis.

Dermatomyositis: factors predicting relapse.

The course of dermatomyositis (DM) can be chronic with relapses, which are associated with major morbidity. The aim of this study was to identify presentation features that predict DM relapses. We retrospectively reviewed data of patients with DM recorded from 1990 to 2011, including muscle biopsy results. Characteristics of patients with and without relapses were compared. Hazard ratios (HRs) were estimated using a Cox model. We identified 34 patients, with a mean age of 46 ± 17 years (range, 18-77) and 24 (71%) women. The muscle and skin abnormalities relapsed in 21 (61%) patients. By univariate analysis, two presentation features were significantly associated with a subsequently relapsing course, namely, dysphonia [HR = 3.2 (1.2-8.5)] and greater skin lesion severity defined as a Cutaneous Disease Area Severity Index [CDASI] > 20 [HR = 3.5 (1.2-7.9)]. Dysphonia and skin lesion severity at disease onset must be recorded, as they significantly predict a relapsing disease course.

G.P.33 - Clinical and pathological features in SMA patients, confirmed by genetic analysis

Spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by degeneration of the anterior horn cells of the spinal cord, resulting in symmetrical limb muscle atrophy and weakness. It is difficult to diagnose SMA patients in some cases, because of its clinical presentations mimicking muscular dystrophies. We aimed to describe clinical and pathologic characteristics of SMA patients, confirmed by genetic test. We reviewed clinical and pathological features of 14 patients, who were completely done with electrodiagnostic study (EDX) and muscle biopsy, and diagnosed as SMA with genetic study from November 1, 2005 to December 31, 2013. Among 14 patients, 8 patients (57.1%) were male. The mean age of symptom onset was 35 months old. Mean age at final genetic diagnosis was 21.1 years old and mean duration between clinical and genetic diagnosis was 7.3 years. All patients showed proximal dominant weakness and their most common first symptoms were both leg weakness. With clinical, EDX and muscle biopsy findings, 10 patients (71.4%) were diagnosed as SMA, but other 4 patients (28.6%) were diagnosed as myopathy. Those 4 patients showed proximal dominant weakness and their first symptoms were both leg weakness, meaning their CK levels were 395 U/L, higher than clinical and pathologically SMA group (45 U/L). Among them (9 patients), EDX showed chronic neurogenic process of 3 patients and myopathic change in 1 patient. Muscle biopsy presented myopathic change with 3 patients, no pathologic diagnosis with 1 patient and neurogenic change in 1 patient. Even though the results of muscle biopsy and electrodiagnostic study show ‘myopathic change’, genetic study of SMN1 gene may show ‘exon 7, 8 deletions’. It is helpful to consider the genetic test for SMN1 gene when we diagnose patients with unspecified neuromuscular disease.

A study of diffusion tensor imaging in Duchenne muscular dystrophy

Objective To observe the white matter and gray matter impairment of Duchenne muscular dstrophy (DMD) patients with diffusion tensor imaging (DTI). Methods Forteen male patients with DMD (6-11 years old) and 10 age-matched healthy boys participated into this study. All patients' diagnosis was based on typical signs and symptoms, serum creatine kinase (CK), electromyography, multiplex ligation-dependent probe amplification (MLPA) for DMD gene test and muscle biopsy results. All participants were scanned by DTI. The fractional anisotropy (FA) values of regions of interest (ROIs), including bilateral parietal lobe white matter, bilateral frontal lobe white matter, genu of corpus callosum, splenium of corpus callosum, bilateral caput nuclei caudati, bilateral anterior cingulate gyrus, bilateral cingulate gyrus, bilateral posterior cingulate gyrus, bilateral lenticular nucleus, bilateral anterior limb of internal capsule, bilateral posterior limb of internal capsule, bilateral thalamus, bilateral occipital lobe whitematter, bilateral temporal lobe white matter, bilateral hippocampus, bilateral superior cerebellar peduncle and bilateral middle cerebellar peduncle, were measured. The data was analyzed and compared between control group and DMD group. Results Compared with control group, the FA value of splenium of corpuscallosum in DMD group was significantly reduced (t = -2.187, P = 0.045). No significant difference was found in FA values of other ROIs between 2 groups (P > 0.05, for all). Conclusions It is found in China for the first time that DMD patients had microstructural changes in splenium of corpus callosum. However, the correlation between this change and cognitive changes of DMD patients remains to be further studied. DOI: 10.3969/j.issn.1672-6731.2015.05.006

Comparison Of Classic Fatigability And Peak Torque Tests Used To Estimate Fast-Twitch Muscle Fiber Composition

Estimation of skeletal muscle fiber type has long been performed through the classic Thorstensson fatigue test. This non-invasive method has strong practical relevance due to its ease of administration and quickness of estimating fast-twitch fiber type percentage (%FT). The classic Thorstensson fatigue test estimation is based on the first three repetitions and the last three repetitions of a leg extension exercise. However, peak torque may not occur within the first three repetitions, reducing the equation’s accuracy. Including the peak torque repetition may improve accuracy of estimation of %FT. PURPOSE: The purpose of this study was to compare the classic Thorstensson fatigability test (CT) with a new peak torque test (PT). METHODS: Twenty-four resistance trained men (age=24.9±1.7 yrs; height=179.6±4.6cm; mass=85.7±11.1kg) volunteered. All volunteers were seated on a Biodex isokinetic dynamometer and performed 50 maximal knee extensions at 180 degrees per second, measuring dynamic peak torque. RESULTS: The new PT estimation of %FT (72.5±6.9) and power slope (-2.8±0.6) were significantly greater compared to the CT estimation of %FT (71.4±7.2) and power slope (-2.7±0.6). CONCLUSIONS: The rate of fatigue of the power slope is used to determine %FT. Our results show that the power slope was greater in the new PT test, thus estimating a greater %FT compared to the CT. These results show individuals may not reach peak torque in the first three repetitions. When administrating fatigability tests, careful consideration should be given to the method used to evaluate the results. Estimation of %FT can help coaches develop proper training programs. Currently the validity of the new PT test is unknown. Future research should verify this test with muscle biopsy results.

Sarcocystis nesbitti causes acute, relapsing febrile myositis with a high attack rate: description of a large outbreak of muscular sarcocystosis in Pangkor Island, Malaysia, 2012.

BackgroundFrom the 17th to 19th January 2012, a group of 92 college students and teachers attended a retreat in a hotel located on Pangkor Island, off the west coast of Peninsular Malaysia. Following the onset of symptoms in many participants who presented to our institute, an investigation was undertaken which ultimately identified Sarcocystis nesbitti as the cause of this outbreak.Methodology/Principal FindingsAll retreat participants were identified, and clinical and epidemiological information was obtained via clinical review and self-reported answers to a structured questionnaire. Laboratory, imaging and muscle biopsy results were evaluated and possible sources of exposure, in particular water supply, were investigated. At an average of 9–11 days upon return from the retreat, 89 (97%) of the participants became ill. A vast majority of 94% had fever with 57% of these persons experiencing relapsing fever. Myalgia was present in 91% of patients. Facial swelling from myositis of jaw muscles occurred in 9 (10%) patients. The median duration of symptoms was 17 days (IQR 7 to 30 days; range 3 to 112). Out of 4 muscle biopsies, sarcocysts were identified in 3. S. nesbitti was identified by PCR in 3 of the 4 biopsies including one biopsy without observed sarcocyst. Non-Malaysians had a median duration of symptoms longer than that of Malaysians (27.5 days vs. 14 days, p = 0.001) and were more likely to experience moderate or severe myalgia compared to mild myalgia (83.3% vs. 40.0%, p = 0.002).Conclusions/SignificanceThe similarity of the symptoms and clustered time of onset suggests that all affected persons had muscular sarcocystosis. This is the largest human outbreak of sarcocystosis ever reported, with the specific Sarcocystis species identified. The largely non-specific clinical features of this illness suggest that S. nesbitti may be an under diagnosed infection in the tropics.

Diagnostic approach to the congenital muscular dystrophies

Congenital muscular dystrophies (CMDs) are early onset disorders of muscle with histological features suggesting a dystrophic process. The congenital muscular dystrophies as a group encompass great clinical and genetic heterogeneity so that achieving an accurate genetic diagnosis has become increasingly challenging, even in the age of next generation sequencing. In this document we review the diagnostic features, differential diagnostic considerations and available diagnostic tools for the various CMD subtypes and provide a systematic guide to the use of these resources for achieving an accurate molecular diagnosis. An International Committee on the Standard of Care for Congenital Muscular Dystrophies composed of experts on various aspects relevant to the CMDs performed a review of the available literature as well as of the unpublished expertise represented by the members of the committee and their contacts. This process was refined by two rounds of online surveys and followed by a three-day meeting at which the conclusions were presented and further refined. The combined consensus summarized in this document allows the physician to recognize the presence of a CMD in a child with weakness based on history, clinical examination, muscle biopsy results, and imaging. It will be helpful in suspecting a specific CMD subtype in order to prioritize testing to arrive at a final genetic diagnosis.