肢体近端肌肉记录的磁刺激运动诱发电位在格林—巴利综合征中…

对１２例格林－－巴利综合征患者进行磁刺激运动诱发电位（ＭＥＰ）测定，记录电极分别放置在肢体近端肌肉（三角肌、肱二头肌、股四头肌）及远端肌肉（指展肌、胫前肌）上，将二者的结果相比较，并与同时进行的肌电图、神经传导速度、Ｆ波进行比较，发现ＭＥＰ阳性率最高，利于早期发现病变；肢体近远端记录的ＭＥＰ阳性率相近，但珠端ＭＥＰ对以近端无力为主的ＧＢＳ患者更为敏感。     

COLQ基因突变致先天性肌无力综合征1例北大核心CSCD

患者男,10岁,从1岁时开始出现波动性进展的运动后肢体无力,神经系统查体:双下肢近端肌力4级,双下肢平举小于5 s下落,单下肢平举小于10 s下落,髂腰肌肌力3级,肌张力减低。重复神经电刺激(repetitive nerve stimulation,RNS)示:低频刺激时波幅递减,四肢运动神经传导(motor conduction velocity,MCV)检查可见重复复合肌肉动作电位(repetitive compound muscle action potential,R-CMAP)。基因检测结果示COLQ基因存在c.393+1G>A和c.655G>A的杂合变异,经Sanger测序验证变异分别来自其父母,诊断为先天性肌无力综合征(congenital myasthenic syndrome,CMS)。予以沙丁胺醇治疗后,患者运动耐力较前增加。报告本例旨在增强临床医生对此疾病的认识,拓宽“肌无力”患者的诊断思路。c.655G>A错义变异既往无报告,可能是CMS的新致病位点。     

术中神经电生理监测和刺激尺神经治疗肘管综合征

目的 评估尺神经松解前置术结合术中超强电刺激治疗肘管综合征的治疗效果.方法 30例中重度肘管综合征患者首先进行尺神经松解前置术,测定并记录松解后小指展肌复合肌肉动作电位(CMAP)的潜伏期及波幅;然后给予尺神经超强电刺激治疗(80 mA,2Hz,10 min),按照同样的方法再次记录小指展肌CMAP的潜伏期及波幅,并将刺激前后的数据进行统计学分析.结果 患者尺神经外膜松解后与超强电刺激后小指展肌CMAP的波幅分别为(2.5±0.4) mV和(6.2±0.8)mV,潜伏期分别为(12.0±0.6)ms和(10.3±0.3)ms,经比较有统计学意义(P＜0.05).超强电刺激后小指展肌CMAP的潜伏期较前平均缩短15.7％,波幅平均增大约2倍.结论 术中超强电刺激对肘管综合征患者的尺神经功能恢复具有辅助治疗作用.     

POEMS综合征电生理特点分析

目的阐明POEMS综合征的电生理特点。方法回顾性分析22例POEMS患者的电生理资料。结果下肢神经的复合肌肉动作电位（CMAP）波幅的降低比上肢更为显著（P〈0．05），运动神经传导速度减慢在下肢更显著（P〈0．05），CMAP及感觉神经动作电位未引出者更常出现在下肢（P〈0．05），79．5％运动神经的远端潜伏期延长，远端潜伏期指数较正常显著增高（P〈0．05），下肢肌的异常肌电表现更易出现（P〈0．05）。结论POEMS综合征周围神经损害更常出现在下肢，且更严重；神经传导速度减慢主要发生于周围神经中间部分而非远端。     

尺神经复合肌肉动作电位改变在吉兰-巴雷综合征和慢性炎性脱髓鞘性周围神经病中的特点

目的：探讨节段和短段刺激尺神经后不同节段复合肌肉动作电位（CMAP）负波各参数变化及传导阻滞在吉兰-巴雷综合征（GBS）和慢性炎性脱髓鞘性周围神经病（CIDP）中的意义。方法：20例GBS和12例CIDP患者行尺神经5点分段刺激（腕、肘下、肘上、腋和Erb＇s点）和短段刺激，记录CMAP负波波幅、时程和面积的变化，分析各参数与临床肌力的相关性。结果：在GBS中，尺神经CMAP负波的时程、波幅和面积的变化在Erb’s点到腕部的各节段中差异很大；波幅与面积的衰减与临床肌力呈高度相关（r=-0.905和-0.907）；传导阻滞多见于近端和肘部，时程离散不明显。在CIDP中，各节段中的参数变化差异不大；远端波幅与临床肌力相关（r=0.586）；传导阻滞在各节段均可出现，常伴明显的时程延长。结论：GBS和CIDP中尺神经CMAP负波的波幅、面积和时程3个参数，可从电生理角度帮助我们认识脱髓鞘疾病的特点。     

重症肌无力的电生理研究

目的探讨重症肌无力（ＭＧ）患者的电生理特征及其诊断价值。方法应用针极肌电图（ＥＭＧ），重复神经电刺激（ＲＮＳ）和激发重复神经电刺激（ＡＲＮＳ）方法，对４７例ＭＧ患者的肌肉和神经肌肉传递功能进行研究。结果部分患者的肌肉见到病理自发电位及短小动作电位，具近端肌分布特征。ＡＲＮＳ阳性率（９０．６％）较ＲＮＳ阳性率（８３．０％）高。Ⅰ型患者肢体肌群存在多项电生理异常。结论适当、综合应用电生理检测技术有助于ＭＧ的早期诊断     

Lambert-Eaton肌无力综合征与癌的相关倾向

Lambert-Eaton 肌无力综合征(LEMS)是一侵害神经肌肉接头的自体免疫性疾病。临床资料表明,大多数LEMS 伴发恶性肿瘤,既往报道癌的发生率为50%～70%。本文报道了过去20年(1969～1991)确诊的28例LEMS,男12,女16。LEMS 的诊断依据包括:肌肉无力(主要是下肢近端肌)与重复收缩后的肌力增加,此外还有反射减低或消失,植物神经功能障碍(通常是口干),而很少有颅神经支配肌的无力。本组病人均有典型的肌电图改变,即单个刺激时呈低波幅多相波,低频重复刺激时波幅降低,而在短时刺激或高频刺激后,波幅显著增高。全组病人分为肿瘤组和非肿瘤组,肿瘤组均由组织学改变做出诊断,非肿瘤组是经至少2年的随访无肿瘤发生者。全组14例伴有肿瘤,均为胸腔肿瘤,其中不典型类     

慢性炎性脱髓鞘性神经病电生理诊断的研究

目的探讨慢性炎性脱髓鞘性神经病（ＣＩＤＰ）的电生理特点。方法对１６例ＣＩＤＰ患者的运动神经１０８条、感觉神经６２条及６８块肌肉进行ＥＭＧ、运动神经传导速度（ＭＣＶ）、远端潜伏期、Ｆ波的出现率、潜伏期及波形，感觉神经传导速度（ＳＣＶ）测定。采用分段刺激记录各段刺激引出的复合肌肉动作电位（ＣＭＡＰ）的波幅、时限和面积，而后进行近端与远端比，从而判断传导阻滞（ＣＢ）及一过性离散（ＴＤ）。结果每例均有３条以上神经受累，上、下肢神经远端潜伏期延长为６２．１％，ＭＣＶ减慢为７０．７％，Ｆ波异常为６９．５％，Ｈ反射异常为３８．９％，ＣＢ、ＴＤ和ＣＢ／ＴＤ异常共５７．０％，其中ＣＢ为２９．３％，腋、肌皮、桡、面神经异常为７３．０％，ＳＣＶ减慢为７２．６％。ＥＭＧ神经源性改变为７３．５％。结论ＣＩＤＰ为广泛的周围神经远、近端损害，近端显著，感觉、运动均受累，存在以脱髓鞘为主伴有轴索变性的电生理改变。电生理的无创性、简便及可重复性使其成为ＣＩＤＰ极为重要的诊断手段。     

POEMS综合征神经传导异常分析

目的 阐明POEMS综合征的电生理特点.方法 对比分析22例POEMS综合征与22例慢性炎症性脱鞘性多发性神经根神经病(CIDP)患者的电生理资料.结果 POEMS组运动神经传导速度(MNCV)较CIDP组减低,但差异无统计学意义(P＞0.05);远端运动潜伏期(DML)明显减低,远端潜伏期指数(TLI)明显增高,差异均有统计学意义(P均＜0.05);POEMS组神经传导阻滞出现率较CIDP组低,差异有统计学意义(P＜0.05);POEMS组胫神经复合肌肉动作电位(CMAP)较CIDP组减低,差异有统计学意义(P＜0.05),而正中神经两组差异无统计学意义(P＞0.05);POEMS组下肢肌异常肌电出现率较上肢高,差异有统计学意义(P＜0.05).结论 POEMS综合征神经传导速度减慢主要在周围神经中间部分,传导阻滞出现率低,神经传导异常可能与上下肢体有关.     

获得性神经性肌强直的临床、电生理及其免疫学异常(附并发于肺癌且有肌无力综合征肌电图特征的神经性肌强直1例报告)

本文报告1例38岁女性肺癌患者伴进行性全身肌肉连续性抽搐、痉挛、僵硬和无力，胸片和胸部CT提示右上肺中心型肺癌、肺不张。脑脊液IgG增高，寡克隆区带阳性。肌电图呈连续性高频肌强直放电，发作间期可见束颤电位。周围神经封闭可缓解全部肌强直症状，并消除肌电图异常连续性放电。低频重复电刺激出现衰减，高频重复电刺激动作电位波幅增高300％。患者同时有神经性肌强直和肌无力综合征肌电图特征，并与中心型肺癌和神经系统免疫学异常并存。上述改变可能与肺癌有关，提示患者神经系统IgG介导的自身免疫异常在神经性肌强直的发病机理中起重要作用。     

Congenital myasthenic syndromes

PURPOSE OF REVIEW: Congenital myasthenic syndromes are a heterogeneous group of diseases caused by genetic defects affecting neuromuscular transmission. In this article, a strategy that leads to the diagnosis of congenital myasthenic syndromes is presented, and recent advances in the clinical, genetic and molecular aspects of congenital myasthenic syndrome are outlined. RECENT FINDINGS: Besides the identification of new mutations in genes already known to be implicated in congenital myasthenic syndromes (genes for the acetylcholine receptor subunits and the collagen tail of acetylcholinesterase), mutations in other genes have more recently been discovered and characterized (genes for choline acetyltransferase, rapsyn, and the muscle sodium channel SCN4A). Fluoxetine has recently been proposed as an alternative treatment for 'slow channel' congenital myasthenic syndrome. SUMMARY: The characterization of congenital myasthenic syndromes comprises two complementary steps: establishing the diagnosis and identifying the pathophysiological type of congenital myasthenic syndrome. Characterization of the type of congenital myasthenic syndrome has allowed it to be classified as caused by presynaptic, synaptic and postsynaptic defects. A clinically and muscle histopathologically oriented genetic study has identified several genes in which mutations cause the disease. Despite comprehensive characterization, the phenotypic expression of one given gene involved is variable, and the aetiology of many congenital myasthenic syndromes remains to be discovered.     

Congenital myasthenic syndrome due to a novel missense mutation in the gene encoding choline acetyltransferase

Congenital myasthenic syndromes are caused by different genetic defects affecting proteins expressed at the neuromuscular junction. Recently, the first molecular genetic defect resulting in a presynaptic congenital myasthenic syndrome has been reported: Recessive loss-of-function mutations in CHAT, the gene encoding choline acetyltransferase, were described in five congenital myasthenic syndrome families. In this study, we investigated three patients from two independent Turkish kinships. Clinically, all patients presented with moderate myasthenic symptoms including ptosis and muscle weakness with increased fatigability. Multiple episodes of sudden apnea were reported for all patients. One child suffering from a second, unrelated disorder, i.e. hepatocellular carcinoma, showed a severe myasthenic phenotype, requiring permanent ventilation. Genetically, we identified a novel missense mutation (I336T) in the CHAT gene homozygously in all three patients. Haplotype analysis revealed that the mutant allele cosegregates with the clinical phenotype in both families (maximum combined two-point LOD-score of 2.46 for D10S1793). In summary, we confirm that CHAT mutations are responsible for a clinically distinct form of congenital myasthenic syndrome, characterized by episodic apnea. Infections and stress may lead to a life-threatening failure of neuromuscular transmission in congenital myasthenic syndrome with episodic apnea. The observation of the same mutation (I336T) in two independent Turkish kinships may suggest a common origin, i.e. founder.     

Slow channel congenital myasthenic syndrome responsive to a combination of fluoxetine and salbutamol

Introduction: Slow channel congenital myasthenic syndrome is a dominant disorder characterized by prolonged acetylcholine receptor ion‐channel activation. Methods: Molecular genetic techniques, electrophysiology, and binding studies in human embryonic kidney (HEK) 293 cells determined mutant function and expression levels. Patient response to treatment was measured by quantitative myasthenic gravis and Medical Research Council grade strength scores. Results: We report an unusual case due to heteroallelic mutations in CHRNE. The slow channel mutation, p.εS278del, is accompanied by a severe low‐expression mutation, p.εR217L, on the second allele. Expression studies and cosegregation of p.εS278del with the disorder in the patient's offspring demonstrate robust expression of the p.εS278del mutation. The patient showed modest benefits from standard treatment with fluoxetine, but there was dramatic improvement when salbutamol was combined with fluoxetine. Conclusions: This case suggests that salbutamol, which is beneficial in some other congenital myasthenic syndromes, might also be considered in addition to fluoxetine in slow channel syndrome. Muscle Nerve, 2013     

Effective Treatment With Albuterol in DOK7 Congenital Myasthenic Syndrome in Children

BackgroundCongenital myasthenic syndromes consist of rare disorders resulting from mutations in genes encoding for presynaptic, synaptic, and postsynaptic proteins that are involved in the signal transmission of the neuromuscular junction. They are characterized by fatigable weakness of the skeletal muscles with symptom onset from birth to early childhood. DOK7 (downstream of tyrosine kinase 7) congenital myasthenic syndrome was previously treated successfully with ephedrine and salbutamol; however, both are unavailable in the United States.MethodsCase report of a child with muscle weakness.ResultsThis report describes a boy who presented only with progressive limb-girdle muscle weakness since age 2 years. The muscle biopsy with extensive studies revealed no obvious etiologies. His muscle weakness rapidly worsened, requiring a wheelchair for daily activities. Expanded neuromuscular gene panel promptly led to the diagnosis of DOK7 congenital myasthenic syndrome, and his muscle strength dramatically and persistently improved in four weeks with albuterol treatment, allowing him to walk independently. In a brief literature review, 15 patients (five treated between ages 5 and 17 years) from the Mayo Clinic with DOK7 mutations were also successfully treated with albuterol.ConclusionDOK7 congenital myasthenic syndrome often presents with limb-girdle muscle weakness, which can become progressive without proper treatment. If muscle biopsy reveals no obvious etiology, an expanded neuromuscular gene panel may lead to a specific diagnosis of congenital myasthenic syndrome such as those due to DOK7 mutation. Albuterol is often used to treat bronchial asthma; however, it can also dramatically and persistently improve the muscle strength of DOK7 congenital myasthenic syndrome.     

Lambert-Eaton Syndrome,an Unrecognized Treatable Pediatric Neuromuscular Disorder: Three Patients and Literature Review

BackgroundLambert-Eaton myasthenic syndrome, a presynaptic neuromuscular junction autoimmune disorder, rarely occurs in children. Patients typically present with proximal lower extremity weakness with areflexia.MethodsWe report three children presenting between ages 9 and 10 years diagnosed with Lambert-Eaton myasthenic syndrome 2 years, 1 year, and 5 months later, respectively. Their clinical attributes are correlated with nine other pediatric Lambert-Eaton myasthenic syndrome patients found in our literature review.ResultsThese patients were identified as having Lambert-Eaton myasthenic syndrome during their evaluation for proximal weakness. Low-amplitude compound muscle action potentials classically facilitating >100% with voluntary exercise and/or 50 Hz stimulation were essential to diagnosis. Three of the 12 children had associated malignancies, two of them had lymphoproliferative disorders with onset of symptoms more rapid than the rest, and the third had neuroblastoma. The nine nonparaneoplastic Lambert-Eaton myasthenic syndrome patients responded to immunomodulatory therapy with close return to their baseline function. Complete remission no longer necessitating medication was reported in two patients. Follow-up up to 17 years was available on two patients previously reported.ConclusionLambert-Eaton myasthenic syndrome is a diagnosis that must be considered in children presenting with unidentified proximal muscle weakness. In most children, Lambert-Eaton myasthenic syndrome is a primary autoimmune disorder that is treatable. Nevertheless, a search for malignancy is recommended.     

Edrophonium responsiveness not necessarily diagnostic of myasthenia gravis

Uneqivocally positive edrophonium tests, both clinically and electrophysiologically, were observed in a classic case of the Lambert-Eaton myasthenic syndrome. A review of the literature revealed that a positive edrophonium response has been reported in a majority of cases of myasthenia gravis (MG) and overlap myasthenic syndrome and in some cases of the Lambert-Eaton myasthenic syndrome, botulism, congenital myasthenic syndrome, drug-induced myasthenic syndrome, the Guillain-Barre syndrome, and amyotrophic lateral sclerosis. From this, we conclude that an unequivocally positive edrophonium test alone is not necessarily diagnostic of MG and that the diagnosis of MG should be based on the clinical features together with edrophonium-responsiveness and other laboratory findings.     

Recurrent COLQ mutation in congenital myasthenic syndrome

Congenital myasthenic syndromes comprise clinically and genetically heterogeneous disorders resulting from presynaptic, synaptic, or postsynaptic defects. Mutations in the COLQ gene result in acetylcholinesterase deficiency and cause a rare, autosomal recessive synaptic form of congenital myasthenic syndrome, with variable age of onset and clinical severity. We present four unrelated patients with a homozygous W148X mutation in the COLQ gene. Signs began at birth in all, but subsequent severity ranged from independent ambulation to wheelchair use during childhood. Treatment was partly effective; one patient was asymptomatic with 3,4-diaminopyridine treatment. These cases illustrate the clinical features and treatment results associated with this particular genotype, which appears to be relatively frequent among Turkish patients with congenital myasthenic syndrome.     

A common mutation (epsilon1267delG) in congenital myasthenic patients of Gypsy ethnic origin.

OBJECTIVE: Mutation analysis of the acetylcholine receptor (AChR) epsilon subunit gene in patients with sporadic or autosomal recessive congenital myasthenic syndromes (CMS). BACKGROUND: The nicotinic AChR of skeletal muscle is a neurotransmitter-gated ion channel that mediates synaptic transmission at the vertebrate neuromuscular junction. Mutations in its gene may cause congenital myasthenic syndromes. A recently described mutation in exon 12 of the AChR epsilon subunit (epsilon1267delG) disrupts the cytoplasmic loop and the fourth transmembrane region (M4) of the AChR epsilon subunit. METHODS: Forty-three CMS patients from 35 nonrelated families were clinically classified as sporadic cases of CMS (group III according to European Neuromuscular Centre consensus) and were analyzed for epsilon1267delG by PCR amplification and sequence analysis. RESULTS: The authors report the complete genomic sequence and organization of the gene coding for the epsilon subunit of the human AChR (accession number AF105999). Homozygous epsilon1267delG was identified in 13 CMS patients from 11 independent families. All epsilon1267delG families were of Gypsy or southeastern European origin. Genotype analysis indicated that they derive from a common ancestor (founder) causing CMS in the southeastern European Gypsy population. Phenotype analysis revealed a uniform pattern of clinical features including bilateral ptosis and mild to moderate fatigable weakness of ocular, facial, bulbar, and limb muscles. CONCLUSIONS: The mutation epsilon1267delG might be frequent in European congenital myasthenic syndrome patients of Gypsy ethnic origin. In general, patients (epsilon1267delG) were characterized by the onset of symptoms in early infancy, the presence of ophthalmoparesis, positive response to anticholinesterase treatment, and the benign natural course of the disease.     

Co-morbidity of Emery–Dreifuss muscular dystrophy and a congenital myasthenic syndrome possibly affecting the phenotype in a large Bedouin kindred

Emery–Dreifuss muscular dystrophy (EDMD) is an X-linked humero-peroneal muscular dystrophy associated with contractures and cardiomyopathy. In a 90 member family, we found 11 affected male individuals, three of whom displayed areflexia and neurogenic electromyographic changes. Muscle biopsy performed in one case demonstrated type grouping suggestive of a neurogenic disorder. These three individuals and another family member, who suffers from mild, static limb weakness but is clinically and genetically unaffected by EDMD showed an abnormal incremental response of over 100% to tetanic stimulation. In contrast, one affected family member showed myopathic features on needle electromyography and no definite pathology in repetitive stimulation studies. The diagnosis of EDMD was established by demonstrating a 1712_1713insTGGGC mutation in the emerin gene. This family apparently expresses co-morbidity of EDMD with an exceptionally mild form of pre-synaptic congenital myasthenic syndrome resembling the Lambert–Eaton myasthenic syndrome (LEMS). The superimposed pre-synaptic disorder may have contributed to the development of the neurogenic features demonstrated in these patients.