CTG-repeat length in distal and proximal leg muscles of symptomatic and non-symptomatic patients with myotonic dystrophy: relation to muscle strength and degree of histopathological abnormalities

Myotonic dystrophy (DM) is an autosomal dominant, multisystemic disorder with a variable phenotypic expression including muscle weakness and myotonia. The muscle wasting is most marked in distal limbs and in facial and neck muscles, although proximal limb muscles become affected as the disease progresses. The CTG-trinucleotide-repeat expansion associated with myotonic dystrophy is usually larger in muscle tissue than in leukocytes. It is unclear whether the repeat length itself bears any relation to the differences in the degree of weakness and atrophy between different muscles. We therefore analysed CTG-repeat lengths in blood and in proximal (m. vastus lateralis) and distal (m. tibialis anterior) muscles of patients with DM (n = 4) and non-symptomatic carriers of the mutant DM allele (n = 2) using conventional Southern blot hybridization. Muscle strength and histopathological abnormalities were evaluated for each muscle. In patients with clinical symptoms, the degree of paresis and morphological abnormalities was markedly more pronounced in m. tibialis anterior than in m. vastus lateralis. In these individuals, the CTG-repeat length was larger in muscles than in leukocytes, whereas in the two non-symptomatic carriers no difference could be detected. Furthermore, there was no clear difference in the repeat length between the two muscles in any of the patients. In conclusion, the selective muscular weakness and atrophy in DM do not seem to be related to differences in CTG-repeat length between different muscles.     

Why is the gracilis muscle relatively uninvolved in neuromuscular disorders?

CT scanning of thigh muscles has shown that the gracilis is often relatively resistant to degeneration in neuromuscular disorders. We have compared the histometric features of the gracilis muscle with the biceps femoris and vastus lateralis muscles in the right and left thighs of 12 subjects without neuromuscular disease. There was striking variation between individuals, but marked similarities between the two limbs in individuals. The gracilis and vastus lateralis muscles contained fewer Type 1 fibres than the biceps femoris. The Type 2 fibres were slightly larger in vastus lateralis than in the other two muscles. There is thus no evident morphological difference between the gracilis muscle and other thigh muscles that can be correlated with the different susceptibility of these muscles in neuromuscular diseases. However, these muscles are subject to differing physiological stresses in movement, and these may be important in determining the response to disease.     

Sleep tonus inversion: a feature of juvenile dystonic parkinsonism

Polysomnographic monitoring of a 16-year-old girl suffering from dopa-responsive dystonic parkinsonism showed a change in the distribution of muscle activity in thigh muscles during different stages of sleep. The hamstring muscles were hypertonic at sleep onset compared with the vastus lateralis of the quadriceps muscles. At the third sleep cycle of each of the 2 nights, the time at which sleep benefit becomes clinically evident, the hypertonia in the hamstring muscles was reversed and the vastus lateralis became more hypertonic. It is suggested that the muscle tonus inversion marks the moment at which the sleep process alleviates the dystonic parkinsonian state manifested at wakefulness as a circardian fluctuation. According to our data, the flexor-extensor tonus inversion during sleep was not yet described in the literature, and may be an associated feature of dopa-responsive dystonic parkinsonism.     

Gene expression and fiber type variations in repeated vastus lateralis biopsies

Introduction: Muscle sample collection can introduce variation in any measured variable due to inter‐ and intramuscle variation. We investigated the variation in gene expression and fiber type composition after repeated biopsy sampling from the vastus lateralis muscle. Methods: Six subjects donated 3 tissue samples each. One hour after baseline sampling from 1 vastus lateralis muscle, samples from both vastus lateralis muscles were obtained. Results: The fiber type composition differed between biopsies taken from the same leg. There were no within‐subject differences in gene expression between the 3 biopsies. Multivariate analysis supports a model in which gene expression differs significantly between individuals but is not affected by repeated muscle biopsy sampling from the same subject. Conclusion: One vastus lateralis muscle sample per subject is sufficient to establish a reliable baseline for comparing gene expression representing selected pathways over time within the same individual. Muscle Nerve 52 : 812–817, 2015     

The neuromuscular junction in response to endurance training.

Endplate and nonendplate cholinesterase and choline acetyltransferase activities were measured in muscles of untrained and endurance-trained rats to determine the relationship of these enzymes to known physiologic and morphologic properties of specific types of muscle fibers, and to determine the responsiveness of these presynaptic and postsynaptic enzymes to chronic muscular activity. In the trained soleus and red and white vastus lateralis, endplate cholinesterase activity was significantly (P < 0.05) higher in the trained than in the nontrained endplate region of the white vastus lateralis muscle only. Endplate cholinesterase activities were greater than nonendplate values in both trained and untrained muscles. Choline acetyltransferase activity in soleus and red and white vastus lateralis was not affected significantly by endurance training. The selective training effect on the cholinesterase activity of the fast-twitch glycolytic fibers contrasts with the small change in oxidative metabolism in fast-twitch glycolytic fibers previously reported in endurance-trained rats.     

DUCHENNE MUSCULAR DYSTROPHY IN YOUNG GIRLS?

Four cases (three sporadic, one familial) of muscular dystrophy (MD) in young girls are presented. The clinical picture was similar to Duchenne MD with onset around two years of age, muscle weakness of pelvic girdle, pseudohypertrophy of the calves (2 cases), contractures of Achilles tendons. Later on, weakness of shoulder girdle and neck flexors developed. Progression was slow. Electrocardiogram was normal in all cases. Buccal smear was positive and serum creatine phosphokinase was high in all cases. Histological biopsy findings (vastus lateralis) were typical for muscular dystrophy with extensive proliferation of endomysial connective tissue. In vitro amino acid incorporation of muscle ribosomes (vastus lateralis) revealed a sixfold increase in the activity of total polyribosomes. Both collagen and noncollagen synthesis of the heavy polyribosomes were significantly increased in all patients. Supplementation of these polyribosomes with normal muscle soluble enzymes restored the synthesis of collagen to control values in one case. The ribosomal findings in our cases are very similar to those found in male Duchenne MD and suggest they might belong to its autosomal recessive variant.     

Neuropharmacology of insects: (Ciba foundation symposium no. 88), by D. Evered,M. O'Connor and J. Whelan (eds.), 330 pages,Pitman, London, £ 22.50, ISBN 0-272-79652-2

A 36-year-old woman presented with a 3-month history of increasing dyspnoea, culminating in respiratory failure due to paralysis of respiratory muscles. She required assisted ventilation. Subsequently, mild limb and neck weakness was noted. Muscle biopsy of the right vastus lateralis showed polymyositis.The patient died suddenly and the postmortem revealed polymyositis with predominant involvement of the diaphragm and intercostal muscles.     

Desminopathy presenting as late onset bilateral facial weakness,with diagnosis supported by lower limb MRI

A 63 year old male presented with a 20 year history of facial weakness and several years of nasal regurgitation and dysphonia. Examination revealed bilateral facial weakness with nasal speech. Serum creatine kinase was 918 U/L. Neurophysiological studies suggested a myopathy and biopsy of the left vastus lateralis showed serpentine basophilic inclusions in the sarcoplasm and strong oxidative enzyme activity suggesting mitochondria accumulation. The muscle MRI showed selective fatty replacement within semitendinosus, gastrocnemius and soleus indicative of a desminopathy. A heterozygous missense variant c.17C>G (p.Ser6Trp) was identified within DES, predicted to be pathogenic in silico and previously described in a family with distal limb weakness. There are no previous case reports of desminopathy presenting with facial weakness, to our knowledge. Diagnosis was suggested following myoimaging of clinically unaffected muscles. Our study highlights the importance of muscle MRI in the diagnostic evaluation of muscle disease and further expands the known phenotypic heterogeneity of desminopathies.     

Phenotype of a limb-girdle congenital myasthenic syndrome patient carrying a GFPT1 mutation

We report a 38-year-old woman who presented with mild proximal dominant muscle weakness and fatigability that fluctuated during menstruation and treatment with ephedrine-containing medication. The patient had been diagnosed with “congenital myopathy with tubular aggregates” by muscle biopsy at age 19. Her revised diagnosis was congenital myasthenic syndrome (CMS) caused by a mutation in GFPT1 (2p13.3 [MIM 610542], c.722_723insG homozygote, CMS-GFPT1) based on a screening gene analysis. Muscle CT revealed diffuse atrophy of proximal and axial muscles focused on the vastus lateralis, hamstrings, medial gastrocnemius and soleus muscles. Oral administration of pyridostigmine bromide clearly ameliorated weakness and fatigability. This is the first reported case of CMS-GFPT1 in Japan. Since CMS symptoms are reactive to treatment, it is important for clinicians to make an accurate diagnosis at an early stage to improve patient QOL. Tubular aggregates in muscle biopsy and day-to-day fluctuations are important features of the disorder. Quantitative muscle strength measurement was effective for evaluating treatment efficacy.     

强直性肌营养不良Ⅰ型临床、病理、骨骼肌磁共振特点

目的总结11例强直性肌营养不良Ⅰ型(DM1)患者的临床、病理和双下肢肌肉受累的特点。方法回顾性分析2012年01月至2020年10月就诊于南京鼓楼医院神经内科的11例DM1患者的临床、骨骼肌活检病理及5例双下肢骨骼肌磁共振的特点。结果11例患者均有不同程度的肌强直、伴有肌无力/肌萎缩症状,肌无力/肌萎缩远端重于近端。骨骼肌病理特点:10/11例患者可见Ⅰ型肌纤维轻度萎缩,部分患者可见核内移、核聚集、肌浆块现象。双下肢肌肉磁共振:5例患者双下肢远端脂肪浸润重于近端,双侧肌肉受累程度不对称,大腿肌肉脂肪浸润以股中间肌最严重,小腿肌肉以腓肠肌、比目鱼肌、腓骨长肌最严重。结论骨骼肌磁共振对诊断强直性肌营养不良Ⅰ型有重要的提示意义。     

A method for positioning electrodes during surface EMG recordings in lower limb muscles

PURPOSE: The aim of this work is to provide information about the degree of inter-subject uniformity of location of innervation zone (IZ) in 13 superficial muscles of the lower limb. The availability of such information will allow researchers to standardize and optimize their electrode positioning procedure and to obtain accurate and repeatable estimates of surface electromyography (sEMG) signal amplitude, spectral variables and muscle fiber conduction velocity. METHODS: Surface EMG signals from gluteus maximus, gluteus medius, tensor faciae latae, biceps femoris, semitendinosus, vastus medialis obliquus, vastus lateralis, rectus femoris, tibialis anterior, peroneus longus, soleus, gastrocnemius medialis and lateralis muscles of ten healthy male subjects aged between 25 and 34 years (average = 29.2 years, S.D. = 2.5 years) were recorded to assess individual IZ location and signal quality. RESULTS: Tensor faciae latae, biceps femoris, semitendinosus, vastus lateralis, gastrocnemius medialis and lateralis showed a high level of both signal quality and IZ location uniformity. In contrast, rectus femoris, gluteus medius and peroneus longus were found to show poor results for both indexes. Gluteus maximus, vastus medialis obliquus and tibialis anterior were found to show high signal quality but low IZ location uniformity. Finally, soleus muscle was found to show low signal quality but high IZ location uniformity. CONCLUSIONS: This study identifies optimal electrode sites for muscles in the lower extremity by providing a standard landmarking technique for the localization of the IZ of each muscle so that surface EMG electrodes can be properly positioned between the IZ and a tendon.     

Diagnostic advantage of needle muscle biopsy and ultrasound imaging in the detection of focal pathology in a girl with limb girdle dystrophy

Ultrasound imaging of the thigh in a 6-year-old girl with limb girdle muscular dystrophy showed striking focal involvement of the vastus intermedius and vastus lateralis muscles, with sparing and hypertrophy of the rectus femoris muscle. This was confirmed on needle muscle biopsy, using the Bergstrom needle, which showed normal histology in the rectus femoris and severe dystrophic change in the vastus intermedius. In neuromuscular disease, it is important to be aware of the possibility of focal muscle involvement, which can be screened for by ultrasound imaging and more effectively investigated by needle than by open muscle biopsy.     

Pseudo-hypertrophic pelvi-crural amyloid myopathy in lambda light-chain myeloma. Clinical, morphological and immunocytochemical study

The case of 65 year old woman with progressive enlargement and "wooden" induration of the pelvic girdle and thigh muscles due to an amyloid infiltration is reported. Muscle changes appeared two years after a diagnosis of myeloma with free lambda light chains. The patient complained of muscle pain, lassitude and weakness. Macroglossia was present. Skeletal muscle (vastus lateralis) contained large amounts of amyloid substance and showed type 2B atrophy. There was no fiber type grouping. Some amyloid deposits abutted on the muscle fiber, destroyed the basal lamina and sarcolemma, but never infiltrated it. Besides the amyloid phagocytosis by macrophages, a relationship between amyloid filaments and fibroblasts was present. Another non-congophilic substance was revealed using the Avidin-Biotin peroxidase complex to localize lambda light chains by light microscopy and corresponded to a granular substance in electron microscopy. Clinicopathological results are discussed with a review of thirteen similar cases previously reported.     

Effects of resistance training on force steadiness and common drive

The purpose of this study was to investigate the influence of an 8-week resistance training program on force steadiness and common drive for the vastus lateralis muscle. Eight untrained men performed a resistance training program. Before the program and at the end of each week, the subjects performed a trapezoid isometric muscle action of the leg extensors, and bipolar surface electromyographic signals were recorded from the vastus lateralis. The signals were decomposed into action potential trains that were cross-correlated to measure common drive. Force steadiness was quantified as the standard deviation of force during the constant-force portion of the trapezoid muscle action. The training program did not consistently affect force steadiness or common drive for any of the subjects. Although future studies are needed with different muscles and training programs, changes in the overall motor control scheme are not likely with resistance training.     

Muscle ultrasound elastography and MRI in preschool children with Duchenne muscular dystrophy

The aim of this study was to determine muscle tissue elasticity, measured with shear-wave elastography, in selected lower limb muscles of patients affected by Duchenne muscular dystrophy (DMD) and to correlate the values obtained with those recorded in healthy children and with muscle magnetic resonance imaging (MRI) data from the same DMD children, specifically the pattern on T1-weighted (w) and short-tau inversion recovery (STIR) sequences. Five preschool DMD children and five age-matched healthy children were studied with shear-wave elastography. In the DMD children, muscle stiffness was moderately higher compared with the muscle stiffness in HC, in the rectus femoris, vastus lateralis, adductor magnus and gluteus maximus muscles. On muscle MRI T1-w images showed fatty replacement in 3/5 patients at the level of the GM, while thigh and leg muscles were affected in 2/5; hyperintensity on STIR images was identified in 4/5 patients. No significant correlation was observed between stiffness values and MRI scoring. Our study demonstrated that lower limb muscles of preschool DMD patients show fatty replacement and patchy edema on muscle MRI and increased stiffness on shear-wave elastography. In conclusion, although further studies in larger cohorts are needed, shear-wave elastography could be considered a useful non-invasive tool to easily monitor muscle changes in early stages of the disease.     

Muscle MRI findings of X-linked spinal and bulbar muscular atrophy

We report here muscle MRI findings of the lower limb in X-linked spinal and bulbar muscular atrophy (SBMA). T1-weighted imaging of muscle MRI disclosed that the thigh muscles, including the semimembranosus, biceps femoris longus and the vastus lateralis muscles, showed high intensity signals with atrophy. Contrarily, the sartorius, gracilis and rectus femoris muscles were comparably preserved. Not only the thigh muscles, but also the calf muscles including the gastrocnemius medialis and lateralis, and soleus muscles showed high intensity signals. In amyotrophic lateral sclerosis (ALS), the leg muscles are generally atrophic, but the selective pattern of fatty degeneration, seen in SBMA was not observed. Muscle MRI is a useful method of estimating the distribution and severity of SBMA in affected muscles.     

Human vastus lateralis and gastrocnemius muscles. A comparative histochemical and biochemical analysis

Two muscles involved in locomotion the vastus lateralis and the gastrocnemius, were compared on a variety of histochemical an biochemical properties. Ten active males, age 20 - 24 years, served as subjects. Fibre type distributions, type I, type IIA and type IIB, as determined from samples extracted by muscle biopsy were similar in both muscles. In addition, no significant difference (p greater than 0.05) was found between fibre types in each muscle for fibre size, relative area, capillaries per fibre and the ratio of capillaries per fibre area. The activities of a number of enzymes representative of energy supplying pathways - the citric acid cycle (succinate dehydrogenase, SHD; beta-hydroxyacyl CoA dehydrogenase, HADH), glycogenolysis (total phosphorylase, PHOSP), glycolysis (phosphofructokinase, PFK) - were of similar magnitude between the two muscles. The only exception noted was for the activity of a glycolytic enzyme, lactate dehydrogenase, LDH, where a 16% higher value was observed in the vastus lateralis. The close degree of homogeneity displayed between these two muscles may be of significance in providing for a functional synchrony to occur in locomotor activities of varying intensity.     

Muscle morphology, enzymatic activity, and muscle strength in elderly men: a follow-up study

A follow-up study of muscle strength, muscle morphology, and enzymatic activity in 23 men, 73-83 years of age, was performed 7 years after the first investigation. With the exception of two men treated for congestive heart failure and four treated for hypertension, all were apparently clinically healthy and none had functional locomotor disturbances. Body weight was reduced by 2% and body cell mass by 6%, whereas the quadriceps muscle strength decreased 10%-22% over the 7-year period. Fiber composition in the vastus lateralis did not change significantly, and there was no significant difference between the biopsies from the biceps brachii and vastus lateralis. In the vastus lateralis, there was a reduction in fast-twitch fiber areas, which were smaller than in the biceps brachii (not studied at the previous investigation). There were also more histopathologic changes in the vastus lateralis than in the biceps brachii. The enzymatic activities of lactate dehydrogenase and myokinase, which were studied on both occasions in the vastus lateralis, did not change, and the activities of the other measured enzymes indicated a maintained metabolic capacity at high age. Oxidative enzymatic activities were higher in the vastus lateralis, and glycolytic enzymatic activities were higher in the biceps brachii, which could partly be explained by differences in relative fiber areas.     

Nonaka肌病临床病理及肌肉磁共振特点分析

目的探讨Nonaka肌病的临床、肌肉病理及肌肉磁共振特点。方法入选2例患者,女性1例,男性1例,临床表现均以双下肢远端肌肉无力、萎缩为主,双上肢仅轻度受累。血清肌酸激酶轻度升高,肌电图提示肌源性损害,神经传导速度均正常。对患者完善大腿及小腿肌肉磁共振检查,并予以左上肢肱二头肌活检,进行组织学、酶组织化学及免疫组织化学染色,抽取外周静脉血2mL送基因公司进行遗传性肌肉病相关基因测序。结果肌肉病理提示,肌纤维肥大、萎缩、再生,肌纤维内可见镶边空泡,符合肌病样病理改变。肌肉MRI提示,大腿股四头肌脂肪化程度较轻,尤其是股外侧肌未受累及,大腿后组肌群及小腿胫前肌、胫后肌脂肪化程度严重。基因结果均提示GNE基因突变。结论 Nonaka肌病是一种与GNE基因突变相关的常染色体隐性遗传性远端肌病,临床表现特点为胫前肌首先受累,而股四头肌早期不受累。病理改变特点为肌纤维内镶边空泡形成。肌肉MRI可提示肌肉脂肪化的程度及分布规律,为诊断提供依据。     

The role of the biarticular agonist and cocontracting antagonist pair in isometric muscle fatigue

Isometric knee extensions until exhaustion at 30%, 50%, and 70% of maximum voluntary contraction were performed by 18 healthy subjects. During muscle fatigue, surface electromyographic activity was recorded from the knee-extensors vastus lateralis, vastus medialis, and rectus femoris, and the coactive antagonistic biceps femoris. The electromyographic parameter median frequency (MF) served as a measure of fatigue. Coefficients of regression of the MF fatigue changes were analyzed statistically. MF fatigue occurred within the coactive biceps femoris and was significantly more pronounced than in the quadriceps. When the MF fatigue shifts of the coactive biceps femoris were compared with each of the three investigated parts of the quadriceps separately, MF fatigue shifts were similar in shape for the biarticular coactive biceps femoris and the biarticular rectus femoris, but differed significantly between the biceps femoris and the two monoarticular muscles, vastus medialis and vastus lateralis. As both the biarticular agonist and coactive antagonist muscles fatigued at a higher rate than the two monoarticular muscles, it seems likely that this biarticular agonist/antagonist pair determines the time to the limit of endurance. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21: 1706–1713, 1998