HTLV‐1–associated myelopathy/tropical spastic paraparesis and peripheral neuropathy following live‐donor renal transplantation

Introduction: Our aim in this study was to provide an updated literature review of electrodiagnostic testing in myasthenia gravis and Lambert–Eaton myasthenic syndrome. Methods: A systematic review of the recent literature was performed using the following key words: myasthenia gravis (MG); Lambert–Eaton myasthenic syndrome (LEMS); electromyography (EMG); repetitive nerve stimulation (RNS); single‐fiber electromyography (SFEMG); nerve conduction study; and normative values. Results: Several articles supported testing of facial, bulbar, and respiratory muscles in the diagnosis of neuromuscular junction (NMJ) disorders, including muscle‐specific kinase antibody (MuSK)‐seropositive MG. Several articles supported use of concentric needle EMG as an alternative to SFEMG jitter in disorders of neuromuscular transmission. A limited number of articles addressed measurement of area (vs. amplitude) decrement in RNS and decreasing the threshold of post‐exercise facilitation. Conclusions: Electrodiagnostic testing continues to be useful for diagnosis of MG and LEMS, although the quality of the evidence is not great. This literature review summarizes RNS and jitter measurement of facial and respiratory muscles and use of concentric needle EMG for SFEMG. Muscle Nerve 52:455–462, 2015     

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.     

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.     

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.     

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。     

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.     

Sensitivity of repetitive facial-nerve stimulation in patients with myasthenia gravis

Repetitive stimulation of the facial nerve is commonly performed in cases of suspected myasthenia gravis (MG) because bulbar weakness is often present, but the most sensitive facial muscle is unknown. We compared the sensitivity of repetitive nerve stimulation (RNS) to the frontalis and nasalis muscles in 244 patients with suspected MG. We found no difference in sensitivity of RNS when recording from these muscles in both ocular and generalized MG. In addition, we confirmed the low sensitivity of RNS for ocular (18%) or generalized (47%) MG. The specificity of facial RNS for both muscles was 100% and, in certain circumstances, may obviate the need for further diagnostic testing.     

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.     

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.     

Seronegative myasthenia gravis: comparison of neurophysiological picture in MuSK+ and MuSK− patients

The aim of this study was to compare the neurophysiological and clinical pictures of a large sample of seronegative myasthenia gravis (SNMG) patients with and without anti-MuSK antibodies. Fifty-two consecutive SNMG patients were retrospectively evaluated. They had undergone an extended neurophysiological evaluation: repetitive nerve stimulation (RNS), single fiber EMG (SFEMG), and electromyography (EMG) with nerve conduction study. A muscle biopsy was performed in 11 of 52 patients, the edrophonium test in 44 of 52 patients and anti-AChR antibodies and anti-MuSK antibodies were tested in all patients. Anti-MuSK antibodies were detected in 25 SNMG patients (48.1%). The number of women in the MuSK+ group was significantly higher (P = 0.01) than in the MuSK- group. Seronegative MuSK+ patients are more severely affected and the deficit often involves the bulbar and the respiratory muscles. No statistically significant differences were observed in the edrophonium test between MuSK+ and MuSK- groups. The RNS test was abnormal in a significantly higher number of MUSK- patients than MUSK+ patients (P < 0.00001). With regard to SFEMG data, MuSK- patients were characterized to have more severe neurophysiological pattern. Our observations showed several differences between the clinical and neurophysiological pictures of MUSK+ and MUSK- patients.     

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.     

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.     

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.     

Trigeminal nerve repetitive stimulation in myasthenia gravis

The aim of this study was to evaluate the utility of repetitive nerve stimulation (RNS) of the trigeminal nerve in assessing patients with myasthenia gravis (MG). In 26 normal controls and 21 patients with myasthenia gravis (MG), 2-Hz repetitive stimulation of the trigeminal nerve was performed using a monopolar needle for percutaneous nerve stimulation and recording over the surface of the masseter. In the MG patients, repetitive stimulation of the ulnar, spinal accessory, and facial nerves was also performed. The mean percent decrement in the compound muscle action potential (CMAP) amplitude among the different nerves at rest were: ulnar, 4.3%; spinal accessory, 10.1%; facial, 14%; and trigeminal, 17.3%. The facial nerve demonstrated abnormal decrement in 57% of all patients, compared with the spinal accessory (48%), trigeminal (43%), and ulnar (20%) nerves. All patients tolerated trigeminal RNS better than or as well as facial RNS. The study demonstrates that trigeminal RNS is a safe, reliable, efficient, and well-tolerated technique that provides another cranial nerve-muscle combination that can be used to supplement repetitive stimulation of other limb or cranial nerves in the evaluation of patients with bulbar or generalized MG.     

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.     

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.     

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.     

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。     

Ocular myasthenia gravis: predictive value of single-fiber electromyography.

Extraocular muscle weakness is the most common presenting sign of myasthenia gravis (MG). More than half of patients presenting with symptoms isolated to these muscles (OMG) develop generalized myasthenia gravis (GMG) over the course of their illness. No clinical, laboratory, or electrophysiological features are recognized that identify these high-risk patients. We have therefore assessed the ability of single-fiber electromyography (SFEMG) to predict the development of GMG in patients presenting with OMG. Thirty-nine consecutive patients presenting with OMG underwent SFEMG of the extensor digitorum communis muscle as well as a battery of other laboratory and imaging studies at the time of diagnosis. All patients were followed prospectively for a minimum of 24 months or until they developed GMG. Two patients were excluded, leaving 37 for assessment. Twenty remained with pure OMG for the entire follow-up period (mean, 55 months). Twenty-six of the 37 had abnormal SFEMG studies at presentation. Eleven of these remained with OMG and 15 developed GMG. Fifty-eight percent of patients with an abnormal SFEMG developed GMG, whereas 82% of those with a normal study remained with OMG. Thus, a normal SFEMG was associated with MG remaining restricted to the extraocular muscles. (P = 0.036, Fisher's exact test), but an abnormal SFEMG was not predictive of subsequent development of GMG.     

Masseteric repetitive nerve stimulation in the diagnosis of myasthenia gravis.

OBJECTIVE: (1) to develop a method for masseteric repetitive nerve stimulation (RNS) and to obtain normative data for amplitude and area decrement of the muscle (M) response. (2) To investigate myasthenia gravis (MG) patients with masseteric RNS. Masticatory muscles are frequently affected in MG, but no RNS test is available to investigate this district. METHODS: Fifteen healthy subjects and 17 MG patients were examined. The masseteric nerve was stimulated by a monopolar needle (cathode), inserted between the mandibular incisure and the zygomatic arch, and a surface electrode (anode), on the contralateral cheek. Masseteric M response was recorded using surface electrodes on the muscle belly and below the mandibular angle. Stimuli were delivered at 3 Hz in trains of 9, at rest and after isometric effort. RESULTS: Normal subjects: mean amplitude decrement was 0.3+/-1.2% at rest, and 1.9+/-1.3% after isometric effort. Patients: 15 patients (88%) were positive on masseteric RNS; in 3 of these it was the only positive RNS test. The extent of decrement observed in masseter muscle was significantly greater than in trapezius muscle. CONCLUSIONS: Masseteric RNS is a simple and well-tolerated procedure; it offers a new possibility in testing the cranial muscles in disorders of neuromuscular transmission.