Clinical pitfalls and serological diagnostics of MuSK myasthenia gravis

Journal of Neurology - We aimed to evaluate the diagnostic accuracy of enzyme-linked immunosorbent assay (ELISA) for anti-muscle specific tyrosine kinase (MuSK) antibody (Ab) in a large cohort of...     

Clinical and laboratory-reconfirmed myasthenia gravis: a population-based study

The aim of this study was to compare the clinically based prevalence of myasthenia gravis (MG) with the prevalence of laboratory-confirmed cases. All patients with a diagnosis of MG living in Estonia as on 1 January 1997 were asked to participate in re-examination. The criteria for laboratory-supported MG were weakness and rapid fatigue and a positive outcome of at least one of three laboratory tests: (i) blinded acetylcholinesterase inhibitor test; (ii) determination of antibodies to acetylcholine receptor and (iii) neurophysiological examination using repetitive nerve stimulation and single-fibre EMG. Eighty-nine patients were re-examined and 70 patients (79%) fulfilled the criteria of laboratory-supported MG. The corrected prevalence ratio was 78 per million. In the non-confirmed MG group, there was more women (92%) than men (43%) whose diagnosis was established within 1 year from onset of symptoms ( P  = 0.016). In all women with non-confirmed MG the diagnosis was established within 1 year from referral to the physician, whereas 68% of women with confirmed MG was diagnosed within 1 year ( P  < 0.0001). Thus, we conclude that, in Estonia the prevalence of MG based on medical records seems overestimated by 21% and women are at higher risk of obtaining an uncertain diagnosis of MG.     

重症肌无力169例临床分析

目的研究重症肌无力(MG)临床特点、误诊原因与MG危象临床表现。方法分析本院收治的169例MG患者的临床资料。结果本文患者均行新斯的明试验,阳性率100%。85例行重复神经电刺激(RNS)检查,64例低频波幅递减,8例同时高频波幅递减。157例行胸腺影像学检查,发现胸腺异常80例。发生肌无力危象31例次。121例行甲状腺功能(FT3、FT4、TSH)检测,发现甲状腺功能异常17例。结论MG临床表现多样,时有误诊,易于合并胸腺瘤或胸腺增生及甲状腺功能异常。肌无力危象发生率高。     

Clinical characteristics and prognosis of very late-onset myasthenia gravis in China

Alteration in onset-age distribution in myasthenia gravis (MG) and its increasing prevalence among the elderly underscores the need for a better understanding of the clinical course of MG and the establishment of personalized treatment. In this study we reviewed the demographics, clinical profile, and treatment of MG. Based on onset age, eligible patients were classified as early-onset MG (onset age ≥18 and <50 years), late-onset MG (onset age ≥50 and <65 years), and very late-onset MG (onset age ≥65 years). Overall, 1160 eligible patients were enrolled. Patients with late- and very late-onset MG showed a male predominance (P=0.02), ocular MG subtype (P=0.001), and seropositivity for acetylcholine receptors and titin antibodies (P<0.001). In very late-onset MG, a lower proportion of patients retained minimal manifestations status or better, a higher proportion of patients had MG-related deaths (P<0.001), and a shorter maintenance time of minimal manifestation status or better was seen at the last follow-up (P=0.007) than that in patients with early- and late-onset MG. Non-immunotherapy may associated with a poor prognosis in patients in the very late-onset group. Further studies on very late-onset MG patients should be performed to evaluate the relationship between immunotherapy and prognosis.     

A cohort study on myasthenia gravis patients in China

Clinical classification and age distribution in myasthenia gravis (MG) cases seem different between Oriental and Caucasian populations, but there have rarely been any clinical studies on MG patients from mainland China. The goal of the current study was to perform a comprehensive survey of myasthenia gravis in a hospital in China, establishing contemporary cohort data and clinical features. 1,108 unselected patients with MG attending the 309th Hospital of PLA, Beijing, China were studied during a 36-month period from July 2008 to June 2011. The sex ratio was 1:1 (F:M). 62.5 % of patients presented as adolescents and adults. Ocular MG cases accounted for 65.6 % childhood MG patients. A positive response was observed in 96.8 % of the patients for neostigmine tests, whereas a positive decremental response to low frequency repetitive nerve stimulation (RNS) was observed in 77.4 % of the patients. The highest stimulating positive rate was 65.3 % in stimulated facial nerve. Thymoma was significantly increased in those patients with severe MG, especially in the cohort involving the respiratory muscles (p < 0.001). The study revealed higher frequency of ocular and childhood MG compared to other studies in USA and European countries, which can be a result of optimum case ascertainment, increased disease duration, or application of complex diagnostic tests. The relative increase in the prevalence of ocular myasthenia can be attributed to the impact of an aging population.     

Clinical study of FK506 in patients with myasthenia gravis

Focal demyelinating lesions typically occur within a 1-cm segment of a nerve. In electrodiagnostic studies, measurements over longer distances decrease the chance of detecting such lesions, but measurements over shorter distances result in greater experimental error. Our objective was therefore to determine the optimal screening distance for ulnar neuropathy at the elbow (UNE) incorporating previously derived experimental errors for calculating nerve conduction velocity (NCV). Using a lesion model wherein prolongation of 0.4 ms was added to the expected latency of a 1-cm nerve segment, new NCVs were derived for distances between 1 and 10 cm for nerves normally conducting between 40 and 65 m/s. Lesion detection, or sensitivity, was defined as the likelihood of calculating a decrease of 10 m/s from the normal NCV while including the experimental error. Specificity was related to the likelihood of an inadvertent calculation of such a decrease in NCV in a segment without a lesion. Sensitivity and specificity were derived at multiple distances with varying NCVs. The total percentage error was the sum of the false-negative and false-positive percentages. The least total percentage error occurred at 3-4 cm, 4-6 cm, and 6-8 cm for nerves normally conducting at 40-50 m/s, 50-60 m/s, and 60-65 m/s, respectively. We conclude that the optimal distance for screening UNE, considering both sensitivity and specificity, is significantly less than 10 cm, perhaps as low as 4-6 cm; considering in addition the likely locations of focal lesions, the best distance is 6-8 cm.     

眼肌型重症肌无力的临床治疗

目的 比较激素和溴吡斯的明在眼肌型重症肌无力(MG)患者中的不同疗效,寻找最佳治疗方法.方法 对2001年12月至2009年1月就诊的初次发病的43例眼肌型MG患者资料进行回顾性研究,根据治疗方式分为溴吡斯的明治疗(A)组6例,溴吡斯的明无效后改用泼尼松治疗(B)组16例,泼尼松治疗(C)组21例,分别选择MG临床绝对评分法的眼肌功能评分和相对评分法对每种治疗方法的疗效进行量化比较.结果 泼尼松治疗期(B+C)前后绝对评分差为7.86±4.28,溴吡斯的明治疗期(A+B)为2.64±2.52(t=-5.2,P<0.01);两者的相对评分(分别为0.76±0.32和0.31±0.30,Z=-4.72,P<0.01)及复发病例数(分别为12例和13例,χ~2=4.02,P=0.045)差异有统计学意义.B组和C组治疗前后疗效无明显差异.结论 激素治疗眼肌型MG的效果优于溴吡斯的明,半年内激素治疗的早晚对治疗效果可能无明显影响.     

合并胸腺瘤的重症肌无力临床研究

目的 探讨胸腺瘤病理分型、病理分期和重症肌无力（MG）之间关系。方法 分析1986-1996年88例经手术证实为胸腺瘤患者,其中28例术前合并MG,分析这28例患者胸腺瘤病理分型、病理分期与MG发生年龄、性别、Osserman临床分型及术后MG缓解加重关系特点。结果 发现胸腺瘤伴有MG28例（31.8%)。其中男18例占64.3%;女10例占35.7%;发病年龄以40-59岁高高峰期,共20例,占71.4%;病理分型证实上皮细胞型胸腺瘤MG发病率高,且临床症状重,以Osserman临床分型Ⅱa,Ⅱb型为主,肌无力危象发生率高,死亡率高;其次为上皮淋巴细胞混合型胸腺瘤,上皮细胞型胸腺瘤术后MG症状缓解后再加重多于混合型胸腺瘤,症状加重多见为上皮淋巴细胞混合型胸腺瘤,上皮细胞型胸腺瘤术后MG症状缓解后再加重比率高。结论 胸腺瘤伴MG患者以男性多见,发病年龄以40-59岁为主,以上皮细胞型为主,Masaoka病理分期为Ⅱ、Ⅲ期胸腺瘤MG临床症状重,且术后MG症状缓解后易再加重。     

Anti-acetylcholine receptor antibodies in myasthenia gravis. Part 2. Clinical and serological follow-up of individual patients

Circulating antibodies to acetylcholine receptor protein (anti-AChR) were measured in the sera collected from 75 patients (53 women, 22 men, ages 9-83 year, 20 with a thymoma) with myasthenia gravis (MG) during 5-44 (mean 25) months. The clinical state of each patient was graded on a 6-point scale. Anti-AChR concentrations were measured by a radioimmunoassay with human antigen. We analysed the relation between the change in clinical state and the change in anti-AChR concentration in 155 periods (1-7, mean 2.1 per patient). The change in clinical state is given as the difference in score at the onset and at the end of this period. The change in anti-AChR concentration is expressed as the percentage of the original concentration at the onset of the period. The results were analysed in relation to the therapy and to the severity of the MG at the onset of each period. A strong correlation between a change in anti-AChR concentration and a change in clinical condition existed during treatment with prednisone or immunosuppression and in the period after thymectomy, while a weaker correlation was present in periods without immunosuppression. In only 3 patients did the changes in anti-AChR concentration precede the clinical change. No changes in anti-AChR concentrations were found if improvement was due to the effect of anticholinesterases or if deterioration was caused by infection or emotion. The serial measurement of anti-AChR may be a valuable method of following the basic trend of the MG in severely affected patients.     

Clinical evaluation and management of myasthenia gravis

Myasthenia gravis (MG) is a syndrome of fluctuating skeletal muscle weakness that worsens with use and improves with rest. Eye, facial, oropharyngeal, axial, and limb muscles may be involved in varying combinations and degrees of severity. Its etiology is heterogeneous, divided initially between those rare congenital myasthenic syndromes, which are genetic, and the bulk of MG, which is acquired and autoimmune. The autoimmune conditions are divided in turn between those that possess measurable serum acetylcholine receptor (AChR) antibodies and a smaller group that does not. The latter group includes those MG patients who have serum antibodies to muscle-specific tyrosine kinase (MuSK). Therapeutic considerations differ for early-onset MG, late-onset MG, and MG associated with the presence of a thymoma. Most MG patients can be treated effectively, but there is still a need for more specific immunological approaches.     

眼肌型重症肌无力临床分析

目的总结分析眼肌型重症肌无力患者的临床特征,以为诊断和治疗提供参考依据。方法回顾性分析113例眼肌型重症肌无力患者的临床资料。采用免疫荧光细胞染色方法检测血清乙酰胆碱受体(AChR)抗体和肌肉特异性受体酪氨酸激酶(MuSK)抗体表达水平,分析这两项免疫学指标对眼肌型重症肌无力向全身型转化的预测价值。结果成年发病的眼肌型重症肌无力好发于40岁以上男性,多以眼睑下垂(95例,84.07%)为首发症状,少数以复视(18例,1 5.93%)起病。疲劳试验和新斯的明试验阳性率分别为79.44%(85/107)和84.85%(84/99),低频重复神经电刺激和血清甲状腺抗体异常率分别为44.32%(39/88)和28%(14/50),胸腺增生和胸腺瘤阳性率分别为16.67%(17/102)和11.76%(12/102);血清AChR抗体阳性率为62.83%(71/113);但MuSK抗体均呈阴性。眼肌型重症肌无力向全身型转化率为12.39%(14/113),其中血清AChR抗体强阳性者(13例,28.26%)显著高于弱阳性者(1例,4%),二者差异有统计学意义(X~2=4.587,P=0.032)。结论成年发病的眼肌型重症肌无力好发于中年以上男性,主要表现为眼睑下垂和复视,大多数患者伴发胸腺和甲状腺异常。血清AChR抗体表达水平升高预示向全身型转化率升高,鲜有MuSK抗体阳性反应。     

眼肌型重症肌无力临床分析

目的总结分析眼肌型重症肌无力患者的临床特征,以为诊断和治疗提供参考依据。方法回顾性分析113例眼肌型重症肌无力患者的临床资料。采用免疫荧光细胞染色方法检测血清乙酰胆碱受体（AChR）抗体和肌肉特异性受体酪氨酸激酶（MuSK）抗体表达水平,分析这两项免疫学指标对眼肌型重症肌无力向全身型转化的预测价值。结果成年发病的眼肌型重症肌无力好发于40岁以上男性,多以眼睑下垂（95例,84．07％）为首发症状,少数以复视（18例,15．93％）起病。疲劳试验和新斯的明试验阳性率分别为79．44％（85／107）和84．85％（84／99）．低频重复神经电刺激和血清甲状腺抗体异常率分别为44．32％（39／88）和28％（14／50）,胸腺增生和胸腺瘤阳性率分别为16．67％（17／102）和11．76％（12／102）;血清AChR抗体阳性率为62.83％（71／113）;但MuSK抗体均呈阴性。眼肌型重症肌无力向全身型转化率为12．39％（14／113）,其中血清AChR抗体强阳性者（13例,28．26％）显著高于弱阳性者（1例,4％）,二者差异有统计学意义（X^2=4．587,P=0．032）。结论成年发病的眼肌型重症肌无力好发于中年以上男性,主要表现为眼睑下垂和复视,大多数患者伴发胸腺和甲状腺异常。血清AChR抗体表达水平升高预示向全身型转化率升高,鲜有MuSK抗体阳性反应。