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.     

Turns-amplitude analysis and motor unit potential analysis in myasthenia gravis

OBJECTIVES: The aims of this study were to investigate myopathic changes in myasthenia gravis (MG) by using turns-amplitude analysis (TAA) and quantitative motor unit potential duration analysis (MUPan), to correlate myopathic changes with severity and duration of the disease and the results of diagnostic tests including repetitive nerve stimulation test (RNS), single fiber electromyography (SFEMG), and anti-acetylcholine receptor antibody (AChR-ab), and to compare the sensitivities of these two methods in detecting myopathic changes in MG. MATERIALS AND METHODS: We studied both MUPan and TAA in 32 patients with MG. RESULTS: The MUPan study showed myopathic changes in 12 patients (37.5%); TAA revealed a myopathic pattern in 4 (12.5%) and a neurogenic pattern in 4 cases (12.5%). Two of the 4 patients with a myopathic change by TAA also had short-duration mean MUP on the MUPan. No statistically significant association was found between the myopathic changes either by MUPan or TAA, and the various clinical and laboratory features. CONCLUSION: We conclude that MUPan is a more sensitive method than TAA in showing myopathic changes in MG, and that TAA is of limited help in demonstrating them.     

RNS与SFEMG在检测ALS患者神经肌肉接头功能紊乱的比较研究

目的探讨重复神经电刺激(RNS)与单纤维肌电图(SFEMG)在检测肌萎缩侧索硬化(ALS)患者神经肌肉接头功能紊乱中的吻合率及RNS低频递减阳性率与SFEMG指标纤维密度(FD)、颤抖(jitter)、阻滞(block)的关系。方法收集2008-5—2009-4在北京协和医院神经科门诊或病房确诊或拟诊的ALS患者43例,同时行RNS及SFEMG检查。比较RNS与SFEMG在判断ALS患者神经肌肉接头紊乱的敏感性和特异性,并分析RNS低频递减与SFEMG参数指标jitter、block、FD的相关性。结果(1)43例患者中26例RNS(+),占60.5%,17例RNS(-),占39.5%。SFEMG(+)34例,占79.1%,SFEMG(-)9例,占20.9%。其中SFEMG(+)+RNS(+)者共25例,SFEMG(-)+RNS(-)者8例。RNS在判断ALS存在神经肌肉接头受累方面与SFEMG比较有一定的吻合性(Kappa=0.47,P0.01)。(2)RNS阴性和阳性组FD间比较无统计学差异(t=-0.1405,P0.05)。RNS阳性组Block程度明显高于RNS阴性组(χ~2=11.432,P0.01),jitter值也明显高于RNS阴性组(t=2.906,P0.01)。桡神经RNS波幅递减程度与jitter值呈正相关(r=0.626,P0.05)。结论 RNS与SFEMG比较有一定的吻合率。RNS检查灵敏度较高,具有操作简单,费用低,耗时短,无创,不需患者特殊配合,近远端肌肉均可操作,易于推广的特点,对ALS患者的辅助诊断具有意义。     

胸腺切除术对重症肌无力患者电生理学指标和临床评分的影响

目的评价胸腺切除术对重症肌无力(MG)的近期疗效。方法对15例MG在胸腺切除术前(平均9天)及术后(平均11天)依次进行了临床绝对评分、右侧腋神经低频重复电刺激(RNS)和右侧伸指总肌单纤维肌电图(SFEMG)检查。结果手术后SFEMG和RNS异常率分别为100%和73%,手术后平均颤抖(jitter)值、异常电位对比例、阻滞电位对比例和临床绝对评分都较手术前有显著的降低;病理为胸腺瘤5例,手术前后平均jitter值、阻滞电位对比例和临床绝对评分均无显著差异,胸腺增生9例,手术后阻滞电位对比例和临床绝对评分较术前显著减低。结论MG患者胸腺切除术后在临床表现和电生理学指标上都有一定程度的改善,但此时大多数患者仍有临床症状和电生理学指标的异常,需要进一步的免疫调节治疗;MG并发胸腺瘤者可能手术后近期疗效差,并发胸腺增生者可能疗效相对较好。     

Repetitive nerve stimulation in myasthenia gravis—relative sensitivity of different muscles

Objective: To correlate repetitive nerve stimulation (RNS) decrement in different muscles with the predominant clinical presentation in myasthenia gravis (MG), and to study single fibre EMG (SFEMG) sensitivity in ocular MG.Methods: Sixty-nine, untreated, consecutive patients suspected for MG were observed prospectively for a minimum of 6 months. Those who improved on medical treatment were diagnosed as MG. The others, in whom the neurophysiological studies were normal and that did not improve on medical treatment served as a control group, from which normative data for RNS and SFEMG was obtained. The MG patients were further classified in 3 subgroups according to the predominant clinical presentation: group I (ocular); group b (bulbar); and group a (axial). We performed RNS in nasalis, trapezius, anconeus, and abductor digiti minimi. All patients with ocular MG underwent jitter determination of the orbicularis oculi muscle.Results: Thirty-seven patients were diagnosed as MG (group I, 15; group b, 13; group a, 9). In group I, RNS was abnormal in 33% of the patients. RNS studies disclosed at least one abnormal muscle response in every patient in groups a and b. Trapezius was significantly more sensitive in group a, and anconeus and nasalis in group b (P<0.01). Jitter was abnormal in all patients in group I, and the most sensitive parameter was an increased number of unstable pairs, 100%.Conclusions: Based on these observations, we recommend that a shoulder muscle, as the trapezius, should be studied first in the limb-axial presentation of MG, and the anconeus–nasalis muscles in predominant bulbar MG. In ocular MG, RNS is not sensitive and jitter should be performed in facial muscles.Significance: This paper shows the unequal sensitivity of several muscles to RNS in different forms of MG.     

Literature review of the usefulness of repetitive nerve stimulation and single fiber EMG in the electrodiagnostic evaluation of patients with suspected myasthenia gravis or Lambert-Eaton myasthenic syndrome

A retrospective literature review of the electrodiagnosis of myasthenia gravis (MG) and Lambert--Eaton myasthenic syndrome (LEMS) through July 1998 was performed for the purpose of generating evidence-based practice parameters. There were 545 articles identified, of which 13 articles met at least three of the six criteria set previously by the American Association of Electrodiagnostic Medicine (AAEM). An additional 21 articles were identified from review articles or the references of these first 13 articles leading to a total of 34 articles. Results of studies utilizing repetitive nerve stimulation (RNS) showed that a 10% decrement in amplitude from the first to fourth or fifth intravolley waveform while stimulating at 2--5 HZ is valid for the diagnosis of MG. The degree of increment needed for the diagnosis of LEMS is at least 25% but most accurate when greater than 100%. Abnormal jitter or impulse blocking are the appropriate criteria for diagnosis of neuromuscular junction (NMJ) disorders when using single fiber electromyography (SFEMG). SFEMG is more sensitive than RNS for the diagnosis of disorders of neuromuscular transmission, but may be less specific and may not be available. Therefore, RNS remains the preferred initial test for MG and LEMS.     

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.     

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.     

Correlation between a patient-derived functional questionnaire and abnormal neuromuscular transmission in Myasthenia Gravis patients.

OBJECTIVE: To correlate the patient-derived physical function score, as measured by the disease specific Myasthenia Gravis Questionnaire (MGQ), and the score obtained with commonly used generic 36-item questionnaire, the Short-Form health survey (SF-36), with the degree of abnormal neuromuscular transmission measured by Single-Fibre EMG (SFEMG) and repetitive nerve stimulation (RNS) in Myasthenia Gravis (MG) patients. METHODS: SFEMG and RNS were performed in the deltoid muscle and SFEMG was also performed in the orbicularis oculi muscle in 45 MG patients. The patients were asked to fill out the MGQ, which has been translated and validated into Swedish, and the SF-36. The sum of MGQ items generates a global MGQ score. Items are also divided into 3 muscle specific domains: generalized, bulbar and ocular. RESULTS: The global MGQ score and generalized domain score of MGQ were strongly correlated with the degree of abnormal neuromuscular transmission, as measured by SFEMG in the deltoid muscle. Scores from ocular and bulbar domains of MGQ were not related to neurophysiological findings. Physical composite scores of SF-36 correlated significantly with the abnormal SFEMG findings in the deltoid. CONCLUSIONS: The degree of disturbed neuromuscular transmission in a proximal limb muscle correlates with a patient's subjective experience of generalized myasthenic dysfunction. SIGNIFICANCE: The observed correlation adds a new dimension to neurophysiological examinations in patients with MG.     

The accessory nerve repetitive nerve stimulation test: a valuable second-line test in myasthenia gravis

The diagnostic usefulness of the accessory nerve repetitive nerve stimulation (RNS) test was evaluated in 100 patients with myasthenia gravis (MG). The test was easy to perform and reliable at the low rates of stimulation. A higher diagnostic sensitivity was found in the accessory nerve RNS test than in the ulnar nerve RNS test on either the abductor digiti quinti or flexor carpi ulnaris muscles, especially in mild generalized MG. Diagnostic sensitivity was significantly increased when RNS test results for three muscles were combined, especially in mild generalized MG and sero-positive MG. In a small number of cases only the ulnar or accessory nerve RNS test was abnormal. There was a good correlation between electrophysiological and clinical severity of MG in the accessory nerve RNS test Thus, we conclude that the accessory nerve RNS test is a valuable second-line test and its greatest usefulness is in cases of mild generalized MG.     

重症肌无力单纤维肌电图测定

57例MG患者和40例健康正常人分别进行了SFEMG检查,部分患者同时进行重复电刺激和SFEMG进行比较。结果发现:MG患者SFEMG阳性率为82.5％。按MG分型:眼肌型阳性率为58.3％,全身型阳性率为100％。而重复电刺激阳性率仅为64％。同时SFEMG的个体MCD均值大小及Jitter阻滞率与病程无关,与病型和病情有关。SFEMG是诊断MG敏感的电生理检查方法。     

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.     

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.     

Evaluation of neuromuscular transmission by using monopolar needle electrode

OBJECTIVE: To evaluate the value of single-fibre electromyography (SFEMG) with monopolar electrode (MNPE) in revealing neuromuscular transmission dysfunction. MATERIAL AND METHODS: We examined the extensor digitorum communis muscle by using single-fibre electrode (SFE) and MNPE sequentially, in randomly assigned 20 healthy volunteers and in 17 patients with known myasthenia gravis (MG). The high-pass filter setting was 3 kHz for MNPE. Ten individual jitter values were calculated for each electrode in every muscle. Repetitive nerve stimulation (RNS) test on trapezius muscle was performed on 15 patients. RESULTS: In controls, the mean jitter values were 27 +/- 9 (10-59) micro s with SFE, and 21 +/- 7.2 (9-56) micro s with MNPE (P = 0.001). In the MG group, the mean jitter values were 52.4 +/- 38 (12-221) micro s with SFE, and 51.8 +/- 34.7 (12-179) micro s with MNPE. Both electrodes identified junction dysfunction in 14 patients. RNS revealed decrement in four patients but 11. CONCLUSION: SFEMG with SFE is still the gold standard; however, SFEMG with MNPE is superior to RNS like SFEMG with SFE.     

Electrophysiologic data on myasthenic syndromes of the Lambert-Eaton type. A series of 23 cases]

The electrophysiological data of 23 adult patients with Lambert-Eaton myasthenic syndrome (LEMS) have been reviewed. Lung carcinoma was disclosed in 17. In six cases with an EMG follow-up ranging between one and 17 years no carcinoma was detected. The results of repetitive nerve stimulation test (RNS) were not statistically different between the 2 groups. Low CMAP ulnar amplitude was present in all patients (mean: 1.7 mV). Decremental response at low rate of stimulation (3 Hz) was present in 17/20 (means: 30%). An abnormal incremental response at high rate of stimulation was present in all cases (mean: 826%). The authors emphasize the interest of a 50 Hz stimulation for 4 s. Increase of the 'F-wave' amplitude was noticed in some cases. Electrophysiological changes suggestive of an associated mild neuropathy were noticed in eight patients but H-reflex was present in 3/3 cases. SFEMG abnormalities were found in 6/6 cases. In one case, stimulated SFEMG showed more blockings and an increased jitter with low rate of stimulation. In one case the electrical pattern of RNS could be misinterpreted as myasthenia gravis in one tested muscle only. The author's results suggest that CMAP amplitude and RNS test could be used to appreciate the short-term improvement of LEMS with treatment and in some cases for the long-term follow-up.     

Surrogate therapeutic outcome measures in patients with myasthenia gravis

Treatment of acquired myasthenia gravis (MG) with immunotherapies successfully relieves symptoms and improves strength as documented by the Quantitative Myasthenia Gravis Score for disease severity (QMGS). Neuromuscular function, as demonstrated by the surrogate measures of repetitive nerve stimulation (RNS) and single-fiber electromyography (SFEMG), is sensitive for diagnosis and staging disease severity. This study of 51 patients treated with immunomodulation confirmed that RNS and SFEMG are useful to stage disease severity, but found that clinical measures such as the QMGS are more sensitive to change than electrophysiological parameters. The presence of blocking on SFEMG did predict responsiveness to intravenous immunoglobulin (IVIG) treatment, providing clinicians with an objective, reliable, quantitative measure to help determine which patients will benefit from this costly treatment.     

The single-fiber EMG in chronic demyelinating neuropathy

Various parameters of single- fiber electromyography (SFEMG) were studied in 19 patients with electrophysiologically and histologically proven chronic demyelinating neuropathy. The mean duration of disease at the time of testing was four years. Motor nerve conduction in the median nerve was abnormal in all patients, whereas sensory nerve conduction was abnormal in all but one. Needle EMG in the extensor digitorum communis (EDC) muscle showed rare fibrillations and fasciculations and some abnormal motor unit potentials in most of patients. SFEMG in the EDC muscle showed an increased fiber density in seven cases (37%) and minimally abnormal jitter in 14 cases (74%). Single-fiber action potentials were stable, whereas blocking was rare. Fiber density was significantly increased in patients with fibrillation in the conventional needle EMG. Our study showed that the SFEMG is mildly abnormal in many patients with demyelinating neuropathy and that this test is useful in detecting and quantitating axonal degeneration in demyelinating neuropathy.     

Neurophysiological and mitochondrial abnormalities in MuSK antibody seropositive myasthenia gravis compared to other immunological subtypes.

OBJECTIVE: To compare the electrophysiological and histopathological features of immunological myasthenia gravis (MG) subtypes. METHODS: Fifty MG patients underwent clinical examination, MuSK-Ab and AChR-Ab analysis. The majority underwent quantitative and single-fiber electromyography (QEMG, SFEMG), repetitive nerve stimulation and deltoid muscle biopsy. From muscle specimens with histological mitochondrial dysfunction, we amplified mitochondrial DNA (mtDNA). In specimens with mtDNA deletions, the nuclear gene POLG1 was sequenced. RESULTS: Five AChR-Ab seropositive [AChR(+)] and 5 seronegative [AChR(-)] patients were MuSK-Ab seropositive [MuSK(+)]. Five of 7 neurophysiologically examined MuSK(+) patients (71%) had proximal myopathic pattern, compared to 7 of 31 MuSK(-)/AChR(+) patients (23%) (P=0.012). SFEMG was abnormal in all examined MuSK(+) patients. All 7 biopsied MuSK(+) and 32 MuSK(-) patients (89%) had cytochrome c oxidase (COX) negative fibers. Three of five MuSK(+) and 13 of 20 MuSK(-) patients analyzed had multiple mtDNA deletions but no POLG1 mutations. CONCLUSIONS: Similar degree of SFEMG abnormalities was present in proximal muscles among MuSK(+) and AChR(+) patients. Proximal myopathy was over-represented in MuSK(+) patients; however, both MuSK(+) and MuSK(-) patients had mild myopathy with frequent mitochondrial abnormalities. SIGNIFICANCE: The weakness in MuSK(+) patients is most likely due to disturbed neuromuscular transmission. The frequently encountered mitochondrial dysfunction in MG warrants further study.     

Decremental response of the nasalis and hypothenar muscles in myasthenia gravis

Repetitive nerve stimulation (RNS) is a standard diagnostic procedure in myasthenia gravis (MG). Although RNS sensitivity is highest in weak muscles, RNS is easier to perform in distal muscles that are often not affected. Twenty-five patients with MG were assessed to compare the sensitivity of RNS of the nasalis muscle to that of the hypothenar muscles. Abnormal decrement was found in hypothenar muscles in 9 patients (36%) and in the nasalis muscle in 13 patients (52%). RNS of the nasalis muscle appeared more useful to detect abnormal neuromuscular transmission in patients with oculobulbar MG (5 of 5) than hypothenar RNS (1 of 5). In patients with generalized MG, hypothenar muscles had a similar yield of abnormal RNS tests.     

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.