Single fiber electromyography of extraocular muscles: A sensitive method for the diagnosis of ocular myasthenia gravis

We performed single fiber electromyography (SFEMG) in the superior rectus and levator palpebralis (SR-LP) muscles of 17 patients with pure ocular myasthenia gravis (MG) and 9 controls. Thirteen patients were also assessed with SFEMG in the orbicularis oculi (OO) muscle. All the MG patients but none of the control subjects showed abnormal SFEMG jitter in the SR-LP muscles. On the other hand, only 62% of the MG patients had abnormal SFEMG jitter in the OO muscle. The procedure was well tolerated by the patients, and complications were minor. We conclude that SFEMG of the SR–LP muscles is a safe and highly sensitive technique for the diagnosis of ocular MG. © 1995 John Wiley & Sons, Inc.     

Autoimmunity in ocular and generalised myasthenia gravis

Restricted ocular myasthenia gravis (OMG) and generalised myasthenia gravis (GMG) have been shown to differ in a number of respects. In OMG, anti-acetylcholine receptor, antistriational and antinuclear antibodies were rare relative to their frequency in GMG. In contrast, antithyroid antibodies and a history of thyroid disease were much more prevalent in OMG than in GMG. OMG was not associated with the female predominance seen in GMG and appeared to be relatively common in some races rather than others. It is suggested that different pathogenetic mechnisms are responsible for these two forms of MG.     

Ocular myasthenia gravis in a senior population: Diagnosis,therapy, and prognosis

The objectives of this study were (I) to explore the prognosis of ocular myasthenia gravis (OMG) in patients with onset at age 70 years and above (i.e. senior persons); (2) to identify predictors of secondary generalization in this age group; and 3) to address the effects of immunotherapy on this population of patients. We performed a retrospective analysis of 39 patients with myasthenia gravis who presented with only ocular signs and symptoms after age 70 years. Generalized myasthenia gravis (GMG) developed in 12 OMG patients (31%). None of the GMG patients required ventilator assistance or a feeding tube. Of the 12 ocular patients progressing to GMG, only one (8%) received immunotherapy prior to generalization. Of those OMG patients who did not progress to GMG, 52% received immunomodulatory therapy. Our senior OMG patients had a prognosis comparable with those of the published data for younger individuals. Although the presence of increased acetylceholine receptor antibody titers and occasionally abnormal repetitive nerve stimulation were useful tools to diagnose OMG, no test was predictive of later generalization. Senior onset OMG patients who received immunotherapy less frequently developed GMG than those not so treated. Muscle Nerve, 2010     

Single fiber EMG in the frontalis muscle in ocular myasthenia: specificity and sensitivity.

Patients (n = 41) with isolated weakness of the eyelids or extraocular muscles, who had been referred for single fiber electromyography (SFEMG), were followed up after 4 to 24 months, At follow-up the patients were classified as "definite ocular myasthenia gravis" (MG), "definite other diagnosis," or "no definite diagnosis" on the basis of the completed investigations and subsequent course. The original SFEMG findings in the frontalis muscle were then reviewed. The specificity and sensitivity of SFEMG for "definite ocular MG" could be maximized by using as criteria for abnormality greater than 8/20 pairs with jitter greater than 45 microseconds, or a mean jitter of 20 pairs of greater than 50 microseconds. Patients with abnormal SFEMG according to these criteria have MG, and are likely to require treatment in the immediate future. Patients who have normal SFEMG according to these criteria (and no other demonstrated disorder) may have MG, but it is so mild that they are unlikely to require treatment. Two patients whose final diagnosis was progressive external ophthalmoplegia had normal SFEMG according to these criteria.     

眼肌型重症肌无力进展为全身型重症肌无力的临床相关因素分析

目的 :探讨眼肌型重症肌无力进展为全身型重症肌无力的临床相关预测因素。方法 :33例初诊为眼肌型重症肌无力的患者经过3年随访,根据疾病进展结局分为眼肌型重症肌无力组(13例)和进展为全身型重症肌无力组(20例)。对与疾病进展可能相关的临床因素进行分析。结果 :进展为全身型重症肌无力组患者初诊时的定量重症肌无力评分、乙酰胆碱受体抗体阳性率、抗核抗体阳性率、合并胸腺瘤的比例以及合并糖尿病的比例均高于眼肌型重症肌无力组(P值均0.05)。结论 :定量重症肌无力评分高、乙酰胆碱受体抗体阳性、抗核抗体阳性以及合并胸腺瘤和糖尿病可能是眼肌型重症肌无力进展为全身型重症肌无力的预测指标。     

Ocular myastyenia gravis: The diagnostic yield of repetitive nerve stimulation and stimulated single fiber EMG of orbicularis oculi muscle and infrared reflection oculography

For the diagnosis of ocular myasthenia gravis (ocular MG), testing of the muscles close to the affected ones may be important. The relative importance of several methods: stimulated single fiber EMG (stimulated SFEMG), repetitive nerve stimulation test (RNS) of orbicularis oculi muscle, and infrared reflection oculography (IROG) was investigated. Thirty-two patients in whom a diagnosis of ocular MG was considered on clinical grounds were admitted to the study. Based on the results of the three neurophysiological tests, the patients could be divided in three groups: a first group with an abnormal stimulated SFEMG, and an abnormal RNS and/or abnormal IROG; a second group with only a slightly abnormal stimulated SFEMG; and a third group with normal tests in all three tests. The clinical diagnosis of ocular MG was made in all 11 patients of the first group; in 86% (6 of 7) of the patients of the second group; and in 7% (1 of 14) of the patients of the third groups. This study demonstrates that the orbicularis oculi muscle is a suitable muscle for stimulated SFEMG in patients with ocular MG, and that the results obtained with this technique showed a better relation with the clinical diagnosis than those of the two other techniques. We also demonstrate that there is no additional value in studying the jitter with different stimulation rates in patients with suspected ocular MG. © 1993 John Wiley & Sons, Inc.     

AAEE minimonograph #25: Single-fiber electromyography in myasthenia gravis

Single-fiber electromyography (SFEMG) demonstrates abnormal jitter in virtually all (99%) patients with myasthenia gravis (MG). One muscle, the extensor digitorum communis, is abnormal in most patients with this disease, but to obtain the maximum diagnostic sensitivity, it may be necessary to examine other muscles, especially ones that are more involved clinically. There is no one muscle that will be more abnormal in every patient with MG. The muscle(s) to be tested must be selected based on the distribution of weakness in the individual patient. Abnormal jitter is also seen in diseases of nerve and muscle; these diseases must be excluded by other electrophysiologic and clinical examinations before diagnosing MG. If neuronal or myopathic disease is present, increased jitter does not indicate that MG is also present. However, if jitter is normal in a muscle with definite weakness, the weakness is not due to MG. When abnormal neuromuscular transmission has been demonstrated by repetitive nerve stimulation, the finding of abnormal jitter does not add to the diagnosis, though it may be useful in providing baseline values for comparison with the results of subsequent studies. SFEMG is most valuable clinically in the patient with suspected MG in whom other tests of neuromuscular transmission and antiacetylcholine receptor antibody titers are normal. Serial measurements of jitter can be useful in following the course of disease and in assessing the effect of treatment, but the results from these studies must always be interpreted in light of the overall clinical picture.     

Anti-MuSK-positive myasthenia gravis: neuromuscular transmission failure in facial and limb muscles

The presence of antibodies against muscle-specific receptor tyrosine kinase (MuSK) appears to define a subgroup of patients with myasthenia gravis (MG) characterized by weakness predominant in bulbar, facial and neck muscles compared with anti-acetylcholine receptor (AChR) antibody-positive MG. To investigate the patterns and severity of neuromuscular transmission failure in different muscles in MuSK-positive MG, we performed single fiber electromyography (SFEMG) in the facial (frontalis) and limb (extensor digitorum communis, EDC) muscles in three anti-Musk-positive patients, and compared results with those of 11 anti-AChR-positive patients. Only one of the three MuSK-positive patients had abnormal jitter in EDC, but all the three showed clearly increased jitter in the frontalis. By contrast, the AChR-positive patients showed similarly abnormal jitter for the two muscles. These results suggest that when the diagnosis of anti-MuSK-positive MG is suspected, SFEMG should be performed in most prominently affected muscles.     

眼肌型及全身型重症肌无力患者外周血T淋巴细胞Fas的表达

目的 探讨Fas介导的细胞凋亡与眼肌型(ocular myasthenia gravis,OMG)及全身型重症肌无力(generalized myasthenia gravis,GMG)发病的关系.方法 采用流式细胞技术检测4例OMG、13例GMG患者及13例健康对照组外周血淋巴细胞中CD4、CD8及Fas的表达.结果 OMG、GMG组与对照组外周血T淋巴细胞表面CD4、CD8分子表达的差异无统计学意义(P>0.05).GMG组与对照组外周血T淋巴细胞中Fas+细胞比例的差异有统计学意义(41.72%±8.73%、31.22%±13.00%,P:0.017).GMG组与对照组Fas表达增高者比例的差异有统计学意义(61.5%、15,4%,P=0.041).Fas表达增高的GMG患者病情较重.病程较长.胸腺瘤发生率较高.OMG与GMG组外周血T淋巴细胞中Fa8+、CD4+Fas+、CD8+Fas+细胞比例差异无统计学意义(P>0.05).结论 GMG患者外周血T淋巴细胞中Fas的表达升高,OMG与GMG患者外周血T淋巴细胞中Fas的表达无显著差异,二者可能同属一种系统性疾病.     

重症肌无力患者汉密尔顿抑郁量表评分分析

目的探讨重症肌无力(myasthenia gravis,MG)患者汉密尔顿抑郁量表(Hamilton depression rating scale,HDRS)评分情况及其影响因素分析。方法横断面研究2013-07—2015-03作者医院就诊的188例MG患者的临床资料和HDRS评分情况,并根据HDRS评分将其分为抑郁组和非抑郁组,分析两组MG患者的临床特点及其与HDRS评分间的关系。结果所纳入MG患者男女比例为1.02∶1,眼肌型重症肌无力(ocular myasthenia gravis,OMG)和全身型重症肌无力(generalized myasthenia gravis,GMG)的比例为1.2∶1,以OMG起病和以GMG起病患者的比例为6.2∶1,病程中位数为2年,四分位数间距为1.8年,平均量化重症肌无力评分(quantitative myasthenia gravis,QMG)为(6.7±2.3)分,平均HDRS评分为(8.7±3.4)分,并发抑郁者65例,未并发抑郁者123例。影响HDRS评分和抑郁发生的相关因素包括性别(P0.01)、MG类型(P0.01)、QMG得分(P0.01)和美国重症肌无力协会(myasthenia gravis foundation of America,MGFA)分型(P0.01)、有无甲状腺功能亢进(P0.05)。结论影响MG患者HDRS评分和抑郁发生的相关因素包括性别、MG类型、QMG评分和MGFA分型、有无甲状腺功能亢进,充分认识其抑郁发生情况有利于更好地治疗MG。     

Diagnostic sensitivity of the laboratory tests in myasthenia gravis.

The diagnostic sensitivity of three laboratory tests [serum antiacetylcholine receptor antibody (AChR-ab) assay, the repetitive nerve stimulation (RNS) test, and, the single fiber EMG (SFEMG)] for myasthenia gravis (MG) was compared in 120 patients. In all cases, at least one of the tests was abnormal. SFEMG was the most sensitive test, being abnormal in 92% of cases, followed by the RNS test (77%) and the AChR-ab assay (73%). SFEMG was abnormal in all cases with negative AChR-ab and RNS tests, in 97% of cases with negative AChR-ab assay, in 89% of cases with negative RNS test, and in 89% of cases with mild MG. We conclude that one of these three tests is abnormal in all cases of MG, and that the SFEMG is most sensitive in the diagnosis of MG.     

Single-fiber electromyography of masseter muscle in myasthenia gravis

Jitter after axonal microstimulation in the masseter muscle was studied in 30 consecutive patients (12 women) with myasthenia gravis (MG). Patients' mean age was 42.3 (12-75), median disease duration was 3 months (1-72), and onset was ocular (15 cases), oculobulbar (7), bulbar (6), or generalized (2). There were 23 newly-diagnosed patients. Nine cases developed purely ocular MG and 21 cases developed generalized MG. In the latter group, five subjects had a rapidly progressive course and 16 subjects had stable or well-controlled disease (MGFA grade 2-3). Six patients did not have circulating anti-acetylcholine receptor antibodies. Masseter single-fiber electromyography (SFEMG) was abnormal in 6 of 9 ocular MG patients and in all generalized cases (overall sensitivity 27 of 30 cases or 90%; confidence interval 79.3%-100.0% at P = 0.95). Masseter should be considered for SFEMG in diagnosis of MG, especially in cases with bulbar onset.     

The effect of cholinesterase inhibitors of SFEMG in myasthenia gravis

We report four patients with myasthenia gravis (MG) in whom single-fiber electromyography (SFEMG) jitter measurements were normal in some muslces while they were taking pyridostigmine and became abnormal 2-14 days after the medication was discontinued. When the abnormality of neuromuscular transmission in MG is mild, cholinesterase inhibitors may mask the findings of increased jitter on SFEMG.     

Ocular myasthenia gravis: treatment successes and failures in patients with long-term follow-up

We previously reported that prednisone reduced the frequency of generalized myasthenia (GMG) and controlled diplopia without major adverse effects at 2 years in patients with ocular myasthenia gravis (OMG). Questions remain as to whether study subjects had long-standing disease, biasing results towards a steroid benefit, and if prednisone merely delayed GMG onset. Here, we performed a record review of a referral neuro-ophthalmology service OMG database for patients who were followed-up for ≥4 years or until GMG developed. We studied the effect of prednisone on GMG incidence and control of ocular symptoms. Generally, patients with diplopia were recommended for prednisone therapy. Most remained on daily 2.5–10 mg for diplopia control. We compared the results for prednisone-treated and “untreated” (pyridostigmine only) patients. Of 87 patients, 55 were in the prednisone-treated and 32 were in the untreated groups. GMG developed in 7 (13%) of the prednisone-treated (OR 0.41; 95% CI 0.22–0.76) and in 16 (50%) of the untreated (OR 2.78; 95% CI 1.68–4.60) patients. After OMG onset, GMG developed at a mean 5.8 and 0.22 years in prednisone and untreated groups. Diplopia was present at the last exam in 27% of the prednisone-treated (mean 7.2 years) and in 57% of the untreated (mean 4.6 years) OMG patients. For 48 prednisone-treated patients who did not develop GMG, OMG treatment failure occurred in 13. Thus, prednisone delays the onset of GMG and has sustained benefit in reducing the incidence of GMG and controlling diplopia. Without prednisone, GMG develops in 50% of OMG patients, typically within 1 year.     

重症肌无力患者外周血AIRE、Tfh细胞和Tfr细胞与病情严重性相关分析

目的探讨自身免疫性调节因子(AIRE)、滤泡辅助性T(Tfh)细胞和滤泡调节性T(Tfr)细胞与重症肌无力(MG)患者病情严重程度的相关性。方法收集2015-12—2016-4第四军医大学唐都医院收治的MG患者22例,根据临床表现分为全身型MG(GMG)和眼肌型MG(OMG);同期选取健康体检中心查体者10名作为健康对照。收集MG患者详细临床资料,包括美国MG协会(MGFA)分型及定量MG(QMG)评分。通过流式细胞术分析AIRE阳性细胞比例及Tfh/Tfr比值。结果 (1)AIRE表达在各组间比较差异具有统计学意义(P0.01)。GMG组和OMG组AIRE表达均较对照组降低(P0.01,P0.05),而GMG组与OMG组间比较差异无统计学意义(P0.05)。(2)Tfh/Tfr比值在各组间比较差异具有统计学意义(P0.01)。GMG组和OMG组Tfh/Tfr比值均高于对照组(P0.01,P0.05),且GMG组高于OMG组(P0.05)。(3)MG患者AIRE表达与MGFA分型及QMG评分呈负相关(r=-0.517,P0.05;r=-0.616,P0.01),Tfh/Tfr比值与MGFA分型和QMG评分呈正相关(r=0.761,r=0.581,均P0.01)。结论 AIRE、Tfh/Tfr比值与MG的病情严重程度有一定的相关性,并可能参与了MG的发病。     

Myasthenia gravis and HLA antigens in American blacks and other races

The association of HLA B8 and DR3 with generalised adult onset myasthenia gravis (GMG) in European Caucasoids is now well established. Studies of the HLA association with myasthenia gravis (MG) in other races might help to determine the location of a critical disease locus. Some previous studies in Japanese, Thais, Asian Indians and Filipinos have been reported. In this study HLA A, B, C and DR typing on 28 American blacks with either GMG or ocular myasthenia gravis (OMG) is reported. A significant increase in both HLA A1 and B8 was detected but there was an increase in DR5 rather than DR3. A review of the HLA antigen frequencies in other races and in D-penicillamine (D-Pen) induced MG suggests that prior claims implicating immune response genes marked by DR3 require review. It seems unlikely that any particular HLA allele is involved directly. Other possibly relevant combinations of alleles or supratypes are suggested. These may provide the basis for future studies of the immunogenetic basis for MG.     

Reliability of SFEMG in diagnosing myasthenia gravis: Sensitivity and specificity calculated on 100 prospective cases

ObjectiveThe study aimed to determine the utility of single-fibre electromyography (SFEMG) in the diagnosis of myasthenia gravis (MG) in subjects with a clinical suspicion of the disease.MethodsWe performed a prospective, single-blinded study on 100 consecutive patients. SFEMG was not considered a criterion in making the MG diagnosis. For all cases, a different physician than the one performing SFEMG made the diagnosis of MG. All subjects underwent standard SFEMG of a single muscle, the orbicularis oculi.ResultsSFEMG was abnormal in 67 of 100 patients. A final diagnosis of definite MG was made in 54 patients (30 men/24 women). SFEMG was positive in 53 of 54 patients diagnosed with MG. The sensitivity of SFEMG in diagnosing MG was 98% (95% CI: 0.94–1.02), while the specificity was 70% (95% CI: 0.54–0.86), with a positive predictive value of 79% (95% CI: 0.74–0.79) and a negative predictive value of 97% (95% CI: 0.94–0.99).ConclusionsIn this cohort of patients, normal SFEMG findings were unlikely to occur in patients with MG.SignificanceSFEMG is not a confirmatory test for the diagnosis of MG, but it has a high negative predictive value in identifying patients without MG.     

神经电生理检查判断眼肌型重症肌无力的敏感度分析

目的：分析眼肌型重症肌无力（OMG）患者的神经电生理特点,为临床诊断提供有价值的依据.方法：对42例临床诊断为OMG患者进行单纤维肌电图、重复神经电刺激和肌电图检测.结果：伸指总肌的单纤维肌电图34例异常,重复电刺激异常23例;肌电图示14例肌源性损害.结论：OMG患者单纤维肌电图是一种敏感度较高的检测方法,其次为重复神经电刺激,其肌肉检测阳性率高低依次为眼轮匝肌、肱二头肌及小指展肌.     

Repetitive hypoglossal nerve stimulation in myasthenia gravis.

OBJECTIVES: To assess the diagnostic efficacy of repetitive nerve stimulation (RNS) of the hypoglossal nerve in patients with myasthenia gravis (MG) and bulbar symptoms (dysphagia, dysarthria). METHODS: Twenty patients with MG and 25 normal controls had RNS of the hypoglossal nerve. All patients also had single fibre electromyography (SFEMG) of the orbicularis oculi and RNS with recordings of the nasalis, trapezius and abductor pollicis brevis muscles. RESULTS: All patients had positive SFEMG studies. Nine patients with bulbar symptoms had positive hypoglossal RNS, including 3 with negative RNS recordings in other muscles. Eleven patients with no bulbar symptoms showed negative hypoglossal RNS, including two with positive RNS recordings from other muscles. CONCLUSIONS: Abnormal RNS of the hypoglossal nerve correlates well with bulbar dysfunction and further characterises the extent of neuromuscular transmission defect in MG patients.     

Repetitive nerve stimulation of facial muscles in MuSK antibody-positive myasthenia gravis

To better define electrophysiological abnormalities in myasthenia gravis (MG) patients with muscle-specific tyrosine kinase (MuSK) antibodies (Ab), we compared electrophysiological features of 14 MuSK Ab-positive, 73 acetylcholine receptor antibody (AChR Ab)-positive, and 22 MuSK and AChR Ab-negative (seronegative) patients with generalized disease. Repetitive nerve stimulation (RNS) abnormalities were observed in 86% of MuSK Ab-positive and 82% of AChR Ab-positive patients but in only 55% of seronegative patients. RNS decrements in the orbicularis oculi were more common and severe in the MuSK Ab-positive patients than the other two groups. Single-fiber electromyography (SFEMG) of the extensor digitorum communis was abnormal in 90% of MuSK Ab-positive patients. The high frequency of RNS abnormalities in facial muscles in the MuSK Ab-positive population reflects the propensity for facial muscle involvement in this form of MG and emphasizes the importance of including facial muscles in RNS protocols when evaluating these patients.