Diagnostic yield of muscle fibre conduction velocity in myopathies

We prospectively assessed diagnostic yield of muscle fiber conduction velocity (MFCV) studies in patients with signs and symptoms suggestive of a myopathy. Results were analysed with respect to the final diagnosis, and compared to the reference standard, which was qualitative electromyography (EMG), turns-amplitude analysis (TAA), and muscle biopsy. We included 125 patients, in whom a myopathy was diagnosed in 71, and a neuromuscular disorder was excluded in 54. Sensitivity of MFCV for the presence of a myopathy was 84%, and specificity 83%. Diagnostic yield of MFCV was superior to EMG, TAA, and muscle biopsy in patients with metabolic myopathies, non-dystrophic myopathies, and channelopathies. We concluded that measurement of MFCV is a quantitative EMG technique with a high diagnostic yield. In certain myopathies, MFCV may be more informative than conventional EMG examination.     

Limb girdle syndromes. Clinical, morphological and electrophysiological studies

The clinical syndrome of slowly progressive proximal limb and limb girdle muscular weakness and atrophy, or limb girdle syndromes (LGS), has a diverse aetiology. Several of the congenital, mitochondrial and other metabolic myopathies and spinal muscular atrophies are recently recognized causes of LGS. Thus the position of limb girdle muscular dystrophy (LGMD) as a discrete entity in the nosology of muscle disease deserves reappraisal. We have therefore reevaluated our experience of 33 patients in this light. Detailed clinical, electrophysiological, and pathological studies including autopsies in 2 cases, were performed. As a result we are confident that LGMD does exist as a sporadic or autosomal dominant (2 families) or recessive condition (2 families). There are therefore probably at least 2 distinct genotypes. Typical LGMD (18 patients in our series) is characterized by slowly progressive symmetrical proximal upper and lower limb girdle weakness and atrophy, elevation of the serum creatine kinase at some stage, dystrophic or less severe myopathic muscle lesions on biopsy, and myopathic EMG findings. Two minor subgroups of LGMD were identified in our series with similar clinical and laboratory features but distinguishable by the development of either facial (4 patients) or by distal limb muscle involvement (3 patients). A further group of patients with sporadic LGS (5 patients) had slowly progressive proximal symmetrical upper and lower limb-girdle weakness and atrophy with myopathic or neurogenic features on either EMG or muscle biopsy so that the precise characterization was difficult. Two of these patients had distal limb muscle involvement and contractures. One patient had upper limb-girdle muscle atrophy with normal lower limbs. A disorder affecting muscle, nerve or both remains a possibility in these cases.     

Diagnostic value of in situ muscle fiber conduction velocity measurements in myopathies

In situ studies on muscle fiber conduction velocity (MFCV) were performed in 54 patients with histologically and biochemically defined myopathies. MFCV was measured over a 10 cm segment of the rectus femoris muscle by intramuscular stimulation and recording. Muscle disorders included muscular dystrophies, myotonic dystrophy, inflammatory myopathies, metabolic myopathies, endocrine myopathies, and congenital myopathies with structural abnormalities. Ten healthy volunteers served as controls. MFCV was significantly reduced in all patients except those with a defect in glycolysis and those that had recovered from acute myositis. MFCV did not vary with either sex, age or the duration of the disease. This shows that MFCV slowing is an unspecific finding in most myopathies. However, in some patients with normal needle electromyography, MFCV provided additional information in diagnosing muscle disease.     

Post-poliomyelitis syndrome: 29 cases]

The post-polio syndrome refers to new neuromuscular symptoms developed by some patients many years after recovery from acute poliomyelitis. Several groups were separated: musculo-skeletal symptoms (different from a new spinal cord disease), infraclinical signs (EMG), post-polio muscular atrophy (new lower motor neuron objective signs) with several subgroups: cramps and fasciculations, benign focal weakness and atrophy (in previously affected muscles or in unaffected muscles), progressive spinal muscular atrophy. The following examination were performed in some cases, but not all, in this retrospective study: muscle CT scan, conventional electromyography (EMG), quantifying-EMG, macro-EMG and single-fiber EMG. The serum titers of neutralising antibodies to polio virus type 1, type 2 and type 3 were negative. No oligoclonal bands were found in the CSF from 6 patients screened by electrophoresis immunoelectrophoresis. Serum creatine kinase or aldolase was high in 6 patients. The same unusual features in this syndrome were observed on muscle biopsies: muscular hypertrophy and interstitial eosinophils; two patients had rimmed vacuoles in the muscle fibers.     

Patterns of selective involvement of thigh muscles in neuromuscular disease

In 14 patients with limb girdle muscular dystrophy, polymyositis, and type 3 spinal muscular atrophy, CT scans of the thigh muscles were correlated with single fiber EMG studies in vastus lateralis, semimembranosus and biceps femoris muscles. There was a relation between the extent of CT scan abnormality and increased fiber density in the three muscles studied, except in the most severely affected muscles in which in some muscles the fiber density values were lower than expected. These results were independent of the underlying pathology. Correlative CT/SFEMG studies provide insights into the pattern of selective involvement of certain muscles in neuromuscular disorders.     

Oculopharyngeal muscular dystrophy and distal myopathy

A family is reported which included a patient with a variant form of oculopharyngeal muscular dystrophy. The patient's son suffered from infantile muscular dystrophy with a distal distribution in the lower extremities and no oculopharyngeal symptoms. Case 1, the father, showed blepharoptosis, but no limitation of ocular movements. Case 2, the son, showed early onset of weakness and more rapid progression of muscle involvement than the father. In both patients EMG, muscle biopsies and elevated serum CPK indicated the myopathic nature of the disorder. A muscle biopsy specimen in Case 2 showed abundant rimmed vacuoles and abnormal filaments 13–19 nm in diameter in the sarcoplasm, usually reported to occur in inclusion body myositis. The findings indicate that oculopharyngeal muscular dystrophy and distal myopathy are related in their etiology and distal myopathy and inclusion body myositis are regarded as variant forms of the same disease.     

Duchenne muscular dystrophy carrier presenting with mosaic X chromosome constitution and muscular symptoms--with analysis of the barr bodies in the muscle

A 53-year-old female with muscular symptoms and incomplete Turner's syndrome was presented. She had two sons with Duchenne type muscular dystrophy (DMD). Her muscular symptoms became apparent at age 52 years, and her elevated serum CK, EMG and pathological findings of the biopsied muscle were consistent with muscular dystrophy. Her cytogenetic analysis from the cultured lymphocytes and fibroblasts showed a 45XO/46XX/47XXX chromosome constitution. Analysis of number of Barr bodies in the muscle specimen revealed that the total number of the bodies were significantly decreased in this case than in the control muscles. The result indicated that nuclei of 45XO karyotype were evidently present in her muscle and contributed to the process of muscle fiber breakdown as a major pathogenetic factor. However, inactivation of normal X chromosome also concerned the pathologic process because there were nuclei with Barr bodies in the damaged fibers as well. Only seven cases with X chromosome mosaicism and muscular symptoms attributable to DMD gene were seen in the literature. Four of them showed rather typical clinical features of DMD, but the muscular symptoms were much milder in the remainder, and patients were still able to walk in their middle lives. It was presumed that the severity of the clinical symptoms was parallel to the ratio of 45XO karyotype in the total number of muscular nuclei.     

进行性脊肌萎缩症129例临床分析

目的探讨进行性脊肌萎缩症(PSMA)的临床特点、诊断与鉴别诊断。方法回顾性分析129例PSMA患者的临床资料。结果本组患者均隐袭起病,逐渐加重,男性多见,发病年龄65.9%患者>50岁。首发症状以单侧上肢无力和肌萎缩为多见(65.9%),均表现为下运动神经元损害的症状和体征,51.9%患者出现延髓麻痹症状;肌电图检查均提示神经源性损害;易误诊为颈或腰椎病。结论本病是一组慢性进行性下运动神经元疾病,病变可累及延髓。诊断主要依据临床表现和肌电图。     

Post-viral fatigue syndrome: evidence for underlying organic disturbance in the muscle fibre

Ten patients with post-viral fatigue syndrome and abnormal serological, virological, immunological and histological studies were examined by the single-fibre electromyographic (EMG) technique after excluding concurrent problems in the neuromuscular system. No abnormality of fibre density was noted but all patients had abnormal jitter values. Very high jitter values were not associated with impulse or concomitant blocking. The findings confirm the organic nature of the disease. A muscle membrane disorder probably arising from defective myogenic enzymes is the likely mechanism for the fatigue and the single-fibre EMG abnormalities. This muscle membrane defect may be due to the effects of a persistent viral infection.     

Freeze-fracture studies of erythrocyte plasma membrane in human neuromuscular diseases

Freeze-fracture studies were conducted in erythrocyte plasma membrane from 8 patients with Duchenne muscular dystrophy (DMD), 8 age-matched controls, 3 adult controls, 10 patients with myotonic muscular dystrophy, and 26 other neuromuscular disease controls. There was marked depletion of intramembranous particles in Duchenne dystrophy, whereas intramembranous particle density counts in other neuromuscular diseases were within normal limits. Therefore, the internal molecular architecture of the erythrocyte membrane is abnormal in Duchenne dystrophy, supporting the concept that a membrane defect involving multiple tissues is present in this disorder.     

糖原累积病的临床电生理、骨骼肌和肝脏病理及基因研究

目的探讨和总结糖原累积病(GSD)的临床病理和基因突变特点。方法回顾性分析18例GSD患者EMG、骨骼肌病理、肝脏病理及二代测序结果。结果GSD慢性起病、波动性,主要表现为四肢近端肌无力,累及膈肌可发生呼吸困难。EMG多为肌源性损害,偶可正常或神经源性损害。骨骼肌活检可见肌纤维胞浆内出现空泡(糖原流失)及嗜碱性颗粒物(糖原蓄积);PAS染色示空泡内异常糖原颗粒沉积。电镜示肌原纤维间糖原贮积伴溶酶体或髓样小体形成。4例患者行肝脏活检示肝细胞肿胀,呈植物细胞壁样镶嵌状排列;胞质内见红色粉尘样物,PAS强阳性证实为糖原。6例患者行二代测序,5例发现GAA杂合突变。7例患者病情迅速进展,5年内死亡;7例缓慢进展,存活5~9年;4例失访。结论(1)GSD早期仅有单纯肌无力症状或低血糖、EMG缺少特异性,多系统受累伴有呼吸困难、肝肿大等提示本病。(2)肌肉和肝脏病理出现大量PAS染色阳性的糖原颗粒对确诊GSD有重要作用。肌活检空泡肌纤维抗线粒体抗体增高提示GSD伴发线粒体代谢紊乱。Dysferlin蛋白免疫组化呈斑片状肌膜和肌质染色,提示钙介导的肌膜融合修复受损可引起继发性肌膜受损。(3)GAA复合杂合突变导致Pompe病(GSDⅡ型)。     

眼咽远端型肌病一家系的咽喉功能观察以及骨骼肌病理特点

目的 报道1个眼咽远端型肌病家系的病理和电生理改变特点,分析其吞咽功能障碍的变化规律.方法 先证者为24岁女性,出现进行性加重的眼外肌麻痹、吞咽困难、构音障碍及四肢远端无力和萎缩2年.肌酸激酶轻度升高.家族同代人中还有5例在20～30岁出现类似症状.对先证者进行纤维咽喉镜吞咽功能检查和肌电图检查,对胫前肌进行肌肉病理检查.结果 纤维咽喉镜检查发现软腭上抬差,肌电图检查发现胫前肌呈现肌源性损害伴随肌强直现象.肌肉病理改变特点是肌纤维出现肥大、萎缩、间质纤维化,部分肌纤维内可见镶边空泡,电镜检查显示肌纤维的胞质内存在管丝包涵体.结论 临床和病理检查证实眼咽远端型肌病的存在,软腭运动障碍是出现咽喉症状的主要原因,此病存在肌强直的电生理改变特点.     

Electromyographic and morphological functional compensation in late poliomyelitis

Patients with prior poliomyelitis may experience muscle function deterioration decades after onset of disease. The present study is aimed at describing electromyographic and morphometric evidence of muscular compensation and of on-going muscular instability. Ten subjects 42-62 years of age with onset of polio 25-52 years earlier were studied with macro EMG, single-fiber EMG (SFEMG), muscle strength measurement, and morphometrical analysis of muscle biopsies from the vastus lateralis muscle. SFEMG revealed increased fiber density (FD) and large macro-MUP potentials indicating pronounced reinnervation as compensation to loss of motor neurons. From electrophysiological data of motor unit size, morphometric measures of fiber size, and muscle strength data, the minimal degree of motor neuron loss was estimated to be greater than 70%.     

Methylation of erythrocyte membrane phospholipids in patients with myotonic and Duchenne muscular dystrophy

Recent studies of rat erythrocyte membranes demonstrated that the transfer of methyl groups to phosphatidylethanolamine significantly altered membrane structure and function. Because membrane alterations were reported in red blood cells from patients with myotonic muscular dystrophy and Duchenne muscular dystrophy, we investigated these reactions as a potential explanation for the membrane defects of these disorders. Human erythrocyte membranes were found to catalyze the transfer of methyl groups from S-adenosylmethionine (SAM) to phosphatidylethanolamine to form successively N-monomethyl-phosphatidylethanolamine (PMME), N,N-dimethylphosphatidylethanolamine (PDME), and phosphatidylcholine (PC). The half-maximal rate of [³H]methyl incorporation into PMME and PDME occurred at lower concentrations of SAM (3 and 11 μM, respectively) than that (46 μm) needed for the incorporation into PC. Phospholipid methyltransferase activities in erythrocyte membranes increased with the age of the subject. Five of seven female patients with myotonic muscular dystrophy possessed elevated rates of phospholipid methylation compared with their sex- and age-matched controls. The formation of PC in the red blood cells of one female patient were enhanced over a wide range of SAM concentrations indicating an increased V_max rather than an altered K_m. In contrast, male patients with myotonic dystrophy or with Duchenne muscular dystrophy had similar activities relative to age- and sex-matched controls. Because only female patients with myotonic muscular dystrophy demonstrated an alteration in phospholipid methylation, these reactions do not represent the primary metabolic defect in either dystrophic disorder. However, these results suggest that an increased conversion of PE to PC may influence the expression of the primary defect especially in older female patients.     

Autosomal recessive distal muscular dystrophy: a comparative study with distal myopathy with rimmed vacuole formation

To clarify the clinical and morphological characteristics of distal muscular dystrophy, clinical and pathological material from 4 affected persons was compared with similar studies in 4 patients with distal myopathy with rimmed vacuole formation. Although these two forms of autosomal recessive distal myopathy with onset in young adulthood were highly similar in their clinical symptoms, histochemical and electron microscopic findings of muscles subjected to biopsy were quite different. The muscle abnormalities in distal muscular dystrophy were almost the same as those in Duchenne muscular dystrophy, showing massive fiber necrosis followed by active fiber regeneration. In contrast, distal myopathy with rimmed vacuole formation showed a progressive muscle fiber atrophy and loss, rimmed vacuoles in the sarcoplasm, and no apparent fiber necrosis or regeneration.     

Restless legs syndrome associated with exercise intolerance: Data from a retrospective observational clinical neuromuscular center study

IntroductionExercise intolerance (EI) is a frequent motive for seeking neuromuscular consultation and may be a sign of metabolic disease or, rarely, muscular dystrophy. The diagnosis is not established in many patients with a typical clinical presentation. Nevertheless, some of them complain of sleep disorders and more especially of restless legs syndrome (RLS).ObjectiveThe objective of our study was to estimate the frequency of RLS in patients presenting with EI.MethodsOur retrospective observational study included all patients seen in the center from 2005 to 2011, who were subsequently investigated for EI in the neuromuscular department of the Caen University hospital. Data were collected on clinical RLS and muscular investigations (creatine kinase [CK], EMG, maximal exercise tests magnetic resonance imaging [MRI] and muscle biopsy obtained along with muscle exploration).ResultsOf the 318 patient records analyzed, 84 showed patients accurately complaining of EI. RLS was diagnosed in 25 of these patients (29.7%). This percentage was significantly higher (P < 0.001) than found in the general population. Improvement was seen in 91.3% of the patients receiving specific treatment.ConclusionRLS can sometimes present with pain, potentially worsening with exercise, inappropriately leading to a hypothesis of EI. Clinicians should thus explore the possible diagnosis of RLS when a muscular disease is not found in patients presenting with such symptoms.     

成人型脊髓性肌萎缩症临床分析(附46例报告)

目的总结分析成人型脊髓性肌萎缩症(SMA4)的临床特征。方法收集46例经肌肉活检证实的SMA4病例进行临床资料回顾性分析。结果SMA4起病隐袭,进展缓慢,肌无力以四肢近端为主,无锥体束受累。约四分之一患者血清CPK轻度升高;EMG示神经源性损害;肌活检主要为小群性肌萎缩,ATP酶染色见同型肌群化及肌纤维代偿性肥大。结论SMA4是病变影响下运动神经元的一组独立性疾病,并非为肌萎缩侧索硬化的某一发展阶段。预后相对良好。     

Neurological aspects of sinoatrial heart block.

The symptoms of 100 patients with chronic cardiac sinoatrial disorder were analysed. The most common presenting features were syncope in 34 cases and dizziness in 22 cases. Over three-quarters of the patients had cerebral ischaemic symptoms at some stage of the disease. Diagnostic difficulties are often encountered and are illustrated by two case histories. Although sinoatrial disorder has been described in association with neuromuscular diseases, only one such example was found in this series. The patient had a limb girdle dystrophy with cardiomyopathy and diffuse disease of the cardiac conducting system. Muscle biopsy samples taken from 11 patients with idiopathic sinoatrial disorder were normal showing no evidence of subclinical muscular disease.     

The distribution and propagation pattern of motor unit action potentials studied by multi-channel surface EMG

We developed the multi-channel surface EMG system using a matrix-type of surface electrode and with the aid of digital signal processing. The subjects were 14 normals (4-50 years) and 2 patients with Duchenne muscular dystrophy (7 and 8 years). The biceps brachii and the tibialis anterior muscles were investigated. The location of the motor end-plates and the measurement of muscle fiber conduction velocity were evaluated by the time shift of bipolar EMG arrays along muscle fibers, or by the distribution map of averaged motor unit action potentials (MUAPs). The lateral extension of a motor unit could be also estimated from the changes of averaged MUAP's amplitudes in the distribution map. Moreover in the biceps of 2 patients with Duchenne dystrophy, the mean muscle fiber conduction velocities were reduced compared to normal subjects, and characteristic propagation patterns of action potentials were obtained. In the 2-dimensional or 3-dimensional distribution map of integrated monopolar EMGs, the high density area agreed with the motor end-plate band.     

肯尼迪病的临床特征与基因突变四例

目的探讨肯尼迪病(KD)的临床特征与基因突变。方法分析4例经基因确诊的KD患者的临床资料。结果 4例患者均为男性,发病年龄分别为35、47、48、36岁,例2有家族史,例4既往双手静止性震颤10余年,4例均以肢体无力起病并以肢体无力为主要症状,例2、例3、例4伴有舌肌萎缩及纤颤,例4伴明显的面部及腹部肌肉跳动。例1初诊未确诊,例2误诊为肌炎,例3误诊为运动神经元病。4例血清肌酸激酶均升高;肌电图(EMG)4例均呈广泛慢性神经源性损害;例1、例2、例3肌肉病理示神经源性损害伴肌源性损害;4例患者雄激素受体基因外显子中CAG重复序列次数均40(分别为53、51、49、52)。结论 KD的临床特点为缓慢进展的延髓和四肢近端肌肉萎缩无力,可伴有内分泌或代谢异常;肌肉病理以神经源性损害为主,多伴肌源性损害。KD临床表现常不典型,需与多种疾病鉴别,基因检测可确诊。