Myopathological features in MELAS syndrome without significant changes in muscle biopsy pathology

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes （MELAS） are common types of mitochondrial encephalomyopathy. The involved muscular pathology is characterized by typical changes of mitochondrial abnormalities. Gene screening has been the gold diagnostic standard for MELAS diagnosis. This study presents three primary MELAS patients, with an age of onset from 13 to 18 years, including one patient with seizure, and two with headache and vomiting. All patients had a family history of disease, with maternal inheritance. Cerebral magnetic resonance imaging revealed abnormally high signals in T2-weighted images： temporal lobe in three cases, occipital lobe in two cases, and parietal lobe in one case. Migrating stroke-like lesions were confirmed in one patient. Muscle biopsy revealed several strongly succinate dehydrogenase-reactive vessels scattered in muscle sections of three patients, but ragged-red fibers and cytochrome c oxidase-negative/dense （COX-/＋） fibers were not observed. Mitochondrial DNA A3243G mutation was identified in all three cases. MELAS syndrome has obvious clinical heterogeneity, and muscle weakness was not prominent in some of the cases. Muscle pathological changes did not accompany ragged-red fibers or COX-/＋ fibers, but succinate dehydrogenase- reactive vessels are important for MELAS diagnosis.

Relevance of muscle biopsy for diagnosing multifocal motor neuropathy

Multifocal motor neuropathy （MMN） is a rare,.focal,inflammatory,demyelinating disease of the peripheral nerves with pure motor involvementJ MMN is clinically characterized by slowly progressive,asymmetric,distal,upper limb predominant weakness,in the absence of sensory disturbances） Weakness is usually multifocal and connected to a distinct motor nerve,such as the musculocutaneous nerve resulting in biceps weakness,the posterior interosseus nerve resulting in finger drop,the median,ulnar,or radial nerve resulting in dexterity problems or grip weakness,or the peroneal nerve resulting in a foot drop.Onset of clinical manifestations is between 20 and 50 years of age.The prevalence of MMN is reported as 1-2 per 100 000.2 MMN is three times more frequent in men as compared to women.

Type ⅡB human skeletal muscle fibers positively correlate with bone mineral density irrespective to age

Background Age-associated decrease in type ⅡA/B human skeletal muscle fibers was detected in human biopsies in our previous study. The relationship between change in muscle fiber typing and bone mineral density （BMD） is, however,unknown either cross-sectionally or longitudinally. We therefore conducted a cross-sectional study to investigate their correlation using human muscle biopsies.Methods Forty human subjects aged （53.4±20.2） years were recruited. Histomorphometric parameters of their muscle biopsies were measured by ATPase staining and image analysis, including average area percentage, fiber number percentage, mean fiber area, and area percentage of connective tissues. Hip and spine BMD was measured by dual-energy X-ray absorptiometry. Partial correlation with adjusting age was performed.Results Type ⅡB muscle fiber was found positively correlated with hip BMD irrespective to age and demonstrated significantly stronger relationship with BMD among all fiber types, in terms of its cross-sectional area （r=0.380, P=0.029）and size （r=0.389, P=0.025）. Type ⅡA muscle fibers associated with hip BMD in mean fiber area only （r=0.420, P=0.015）.Conclusions Type ⅡB muscle fiber may play an important role in maintaining bone quality. This may also be a relatively more sensitive fiber type of sarcopenia and osteoporosis. These findings further consolidate the muscle-bone relationship.

Skeletal Muscle Fiber Type and Morphology in a Middle-Aged Elite Male Powerlifter Using Anabolic Steroids

Powerlifting regularly exposes athletes to extreme stimuli such as chronic heavy resistance training(HRT),and many powerlifters choose to augment their performance with anabolic-androgenic steroids(AAS).However,little is known about the myocellular adaptations that occur from long-term HRT and AAS use,especially into middle age.We were presented with the unique opportunity to study muscle cells from an elite-level powerlifter(EPL;age 40 years)with≥30 years of HRT experience and≥15 years of AAS use.The purpose of this case study was to identify myocellular characteristics[myosin heavy chain(MHC)fiber type,fiber size,and myonuclear content]in EPL,as well as compare these data to existing litera-ture.The participant underwent a resting vastus lateralis muscle biopsy and single fibers were analyzed for MHC content via SDS-PAGE.A subset of fibers underwent MHC-specific imaging analysis via confocal microscopy to identify cell size(cross-sectional area,CSA)and myonuclear domain(MND)size.MHC fiber type distribution was 9% I,12% I/IIa,79% IIa,and 0% other isoforms.This pure MHC IIa(fast-twitch)fiber content was amongst the highest reported in the literature.Imaging analysis of MHC IIa fibers revealed a mean CSA of 4218±933μm^(2) and MND of 12,548±3181μm^(3).While the fast-twitch fiber CSA was comparable to values in previous literature,mean MND was smaller than has been reported in untrained men,implying greater capacity for growth and repair.These findings showcase the unique muscle cell structure of an elite powerlifter,extending the known physiological limits of human muscle size and strength.

Progress in Diagnosing Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like Episodes

Objective： Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes （MELAS） is a progressive, multisystem affected mitochondrial disease associated with a number of disease-related defective genes. M ELAS has unpredictable presentations and clinical course, and it can be commonly misdiagnosed as encephalitis, cerebral infarction, or brain neoplasms. This review aimed to update the diagnosis progress in MELAS, which may provide better understanding of the disease nature and help make the right diagnosis as well. Data Sources： The data used in this review came fi-om published peer review articles from October 1984 to October 2014, which were obtained fiom PubMed. The search term is ＂MELAS＂, Study Selection： lnfornmtion selected from those reported studies is mainly based on the progress on clinical tkatures, blood biochemistry, neuroimaging, muscle biopsy, and genetics in diagnosing MELAS. Results： MELAS has a wide heterogeneity in genetics and clinical manifestations. The relationship between mutations and phenotypes remains unclear. Advanced serial functional magnetic resonance imaging （MRI） can provide directional information on this disease. Muscle biopsy has meaningflil value in diagnosing MELAS, which shows the presence of ragged red fibers and mosaic appearance of cytochrome oxidase negative fibers. Genetic studies have reported that approximately 80% of MELAS cases are caused by the lnutation in.3243A〉G of the mitochondrial transfer RNA （Leu （UU R）） gene （MT-TLI）. Conclusions： MELAS involves multiple systems with variable clinical symptoms and recurrent episodes. The prognosis of MELAS patients depends on timely diagnosis. Therefore, overall diagnosis of MELAS should be based on the maternal inheritance family history, clinical manifestation, and findings from serial MR1, muscle biopsy, and genetics.

Absent MicroRNAs in Different Tissues of Patients with Acquired Cardiomyopathy

MicroRNAs （miRNAs） can be found in a wide range of tissues and body fluids, and their specific signatures can be used to determine diseases or predict clinical courses. The miRNA profiles in biological samples （tissue, serum, peripheral blood mononuelear cells or other body fluids） differ significantly even in the same patient and therefore have their own specificity for the presented condition. Complex profiles of deregulated miRNAs are of high interest, whereas the importance of non-expressed miRNAs was ignored. Since miRNAs regulate gene expression rather negatively, absent miRNAs could indicate genes with unaltered expression that therefore are normally expressed in specific compartments or under specific disease situations. For the first time, non-detectable miRNAs in different tissues and body fluids from patients with different diseases （cardiomyopathies, Alzheimer＇s disease, bladder cancer, and ocular cancer） were analyzed and compared in this study, miRNA expression data were generated by microarray or TaqMan PCR-based platforms. Lists of absent miRNAs of primarily cardiac patients （myocardium, blood cells, and serum） were clustered and analyzed for potentially involved pathways using two prediction platforms, i.e., miRNA enrichment analysis and annotation tool （miEAA） and DIANA miRPath. Extensive search in biomedical publication databases for the relevance of non-expressed miRNAs in predicted pathways revealed no evidence for their involvement in heart-related pathways as indicated by software tools, confirming proposed approach.

The R168G heterozygous mutation of tropomyosin 3 (TPM3) was identified in three family members and has manifestations ranging from asymptotic to serve scoliosis and respiratory complications

According to existing reports,mutations in the slow tropomyosin gene(TPM3)may lead to congenital fiber-type disproportion(CFTD),nemaline myopathy(NM)and cap myopathy(CD).They are all congenital myopathies and are associated with clinical,pathological and ge-netic heterogeneity.A ten-year-old girl with scoliosis was unable to wean from mechanical ventilation after total intravenous anesthesia.The girl has scoliosis,respiratory insufficiency,motion delay and muscle weakness;her younger brother has a similar physiology but does not have scoliosis or respiratory insufficiency,and her parents are healthy.We conducted genetic testing and found a c.502C>G(p.R168G)heterozygous mutation in the family.This mutation originated from the father and was autosomal dominant.Muscle biopsy results indicated that no special structures were present,and the type I fiber ratio was not notably high compared to previous reports.Although the family members have the same mutations,their clinical mani-festations are quite different.