Concentric and single fiber needle electrodes yield comparable jitter results in myasthenia gravis

The single fiber needle electrode (SFNE), which is designed to isolate single muscle fiber action potentials, has played an important role in the diagnosis of myasthenia gravis (MG). However, the concentric needle electrode (CNE) has been recently adopted by some workers to study neuromuscular instability in MG, and reference data have also been obtained in healthy subjects. In this study we wanted to establish whether data acquired using the SFNE is comparable to that obtained using the CNE when studying patients with MG. We established reference data for our laboratory using the CNE for orbicularis oculi (OO) and extensor digitorum communis (EDC). We compared data from 24 MG patients using both SFNE and CNE and found no significant differences in mean jitter values for either muscles. We correlated the neurophysiological data obtained by either electrode with various clinical assessments, the ice pack test, OO and EDC strength measurement, and MGFA classification of disease, and we found no significant relation. We compared discomfort scores for the two needle electrodes for each muscle and found that the discomfort scores for CNE are significantly lower (P = 0.0004). We conclude that the CNE is a useful alternative electrode for studying single fiber potentials, but more reference data from normal control subjects is desirable. Muscle Nerve, 2008     

Single-fiber EMG with a concentric needle electrode: validation in myasthenia gravis

We performed a retrospective study to validate whether a disposable concentric needle electrode (CNE) can be used in place of a single-fiber (SF) electrode for jitter measurements in myasthenia gravis (MG). Normal values for voluntary contraction of orbicularis oculi (OO) and extensor digitorum communis (EDC) were collected from 20 healthy subjects. The method was validated by a retrospective analysis of 56 consecutive MG patients, the "gold standard" being a positive acetylcholine receptor (AChR) antibody titer at the time of the electrophysiological (electromyography) study and the clinical diagnosis. Receiver operating characteristic (ROC) curves were constructed to define maximal sensitivity and specificity of the technique. The sensitivity was 96.4% (95% confidence interval 87.5%-99.6%), with no false-positive results, similar to traditional SF EMG and confirming that the disposable CNE is a justifiable alternative.     

Characterization of acetylcholine receptor antibodies in a patient with primary biliary cirrhosis

Antibodies against the acetylcholine receptor were found in a patient with primary biliary cirrhosis. The patient had no clinical or electrophysiological evidence of disturbed neuromuscular function. The antibodies were of both IgG and IgM isotype. Following passive transfer, these antibodies showed the same capacity to bind in vivo to mouse muscle receptors as immunoglobulins from patients with myasthenia gravis. The affinity of the antibodies was high and comparable to that found in myasthenia gravis patients.     

Single-fiber electromyography in limb and facial muscles in muscle-specific kinase antibody and acetylcholine receptor antibody myasthenia gravis

We examined the findings from single-fiber electromyography in extensor digitorum communis (EDC) and orbicularis oculi (OOc) in 13 myasthenia gravis (MG) patients with muscle-specific kinase antibodies (MuSK-MG) and 12 MG patients with acetylcholine receptor antibodies (AChR-MG) with similar clinical scores. More than 70% of AChR-MG patients had abnormal jitter in both EDC and OOc, but the majority of MuSK-MG patients had normal jitter in EDC despite abnormal jitter in OOc. These findings demonstrate clear differences between the neurophysiology of MuSK-MG and AChR-MG.     

Effect of myasthenic IgG on degradation of junctional acetylcholine receptor

We investigated the effect of the lgG from patients with myasthenia gravis (MG) on the degradation of normal rat junctional acetylcholine receptor (AChR) labeled with ¹²⁵l-α-bungarotoxin (BuTx) and calculated the degradation rate (DR). The DR for the lgG from these patients was significantly higher than that from healthy volunteers and patients with other autoimmune diseases. For MG, DR was significantly correlated with the severity of the disease but not with anti-AChR antibody titer. DR was accelerated by lgG from patients with generalized MG whose antibody titers were in the normal range and by lgG from patients with ocular MG. These results indicate that measurement of the DR of junctional AChR in normal rats is more closely correlated with the severity of the disease than is measurement of anti-AChR antibody and that the former is a sensitive and confirmatory method for evaluating MG. © 1993 John Wiley & Sons, Inc.     

Acetylcholine receptor antibody in myasthenia gravis

Radioimmunoassay techniques were used to detect antibodies to the acetylcholine receptor (AAChR) in 164 patients with adult-onset myasthenia gravis. AAChR levels above 0.6 nM/l were considered pathological and were found in 67% of the patients with an average value of 58.99 +/- 125.02 nM/l (0.6-900.0). Correlation, with clinical functional status, the histopathological thymus alterations and the different therapeutics used did not disclose any statistically significant differences.     

The B-cell repertoire in myasthenia gravis includes all four acetylcholine receptor subunits

By enumerating cells secreting IgG antibodies of particular specificities using an enzyme-linked immunospot (ELISPOT) assay, the B-cell responses to Torpedo acetylcholine receptor (AChR) and its α-, β-, γ- and δ-subunits in peripheral blood from patients with myasthenia gravis (MG), and controls with other neurological diseases (OND) as well as healthy subjects were determined. Compared to controls, the patients with MG had elevated numbers of B cells secreting antibodies against AChR and its α-, β-, γ- and δ-subunits in peripheral blood in parallel. The mean numbers of anti-AChR antibody secreting cells were about 17 per 10⁵ blood MNC, and for the subunits 10 to 15 in MG patients, compared to between 0.8 and 1.9 per 10⁵ blood MNC in OND patients, and 0.1 to 0.3 in healthy controls. Such B cells detected in controls probably represent naturally occurring B cells responded to AChR and its subunits. The finding that most (60%) MG patients had B cells predominantly recognizing the α-subunit may be an indirect argument for the existence of a main immunogenic region (MIR). In the remaining 40% of patients with MG the predominant B-cell responses were directed to β-, γ- or δ-subunit. The data suggest that all four AChR subunits may function as strong immunogens in MG, though the α-subunit may be the major immune target in a substantial proportion of MG patients.     

Immunochemical properties of junctional and extrajunctional acetylcholine receptor

Immunological assays were performed to compare two distinct forms of the nicotinic acetylcholine receptor (AChR): junctional (JR) and extrajunctional receptor (EJR). Antibodies from myasthenia gravis patients' sera inhibited the binding of [¹²⁵I]α-bungarotoxin (BGT), to EJR more effectively than binding to JR. Immunological differences between JR and EJR were confirmed by other assay methods. In all cases, EJR appeared to have antigenic determinants not found on JR. It was established that enzymatic removal of carbohydrates from EJR caused it to more closely resemble JR. Thus differences between JR and EJR may be due, in part, to carbohydrate residues found on EJR that are absent on JR. The extent of antibody binding to EJR was examined by gel filtration methods. Immunochemical studies of bands from SDS gels showed that antibodies are present in myasthenic serum which react with the 3 subunits (42, 53, 64 kdaltons) of AChR to varying degrees.     

Myotonic dystrophy type 1 coexisting with myasthenia gravis and thymoma

Myotonic dystrophy type 1 (DM1) is an autosomal-dominant multisystemic disorder that may rarely be associated with benign and malignant neoplasms. Cases of both thymoma and myasthenia gravis in association with DM1 are extremely rare. A literature review revealed only three prior reports. We present a 51-year-old man with a family history of DM1 and fluctuating diplopia and ptosis, who was found to have acetylcholine receptor-binding antibodies, thymoma, and a clinical presentation compatible with ocular myasthenia gravis as well as positive genetic testing for DM1. Needle electromyographic (EMG) study demonstrated diffuse runs of myotonic discharges in multiple muscles, consistent with the diagnosis of DM1. Single-fiber EMG showed both increased jitter and blocking. Due to somatic instability, which has been shown previously in DM1, the myotonin protein kinase (DMPK) gene appears to act as a tumor suppressor. Therefore, abnormal CTG repeat expansions in the gene could lead to the development of thymoma and myasthenia gravis.     

Concentric needle jitter on stimulated frontalis and extensor digitorum in 20 myasthenia gravis patients

Introduction: Our objective was to study jitter parameters using a concentric needle electrode (CNE) in the extensor digitorum (ED) and frontalis (FR) muscles. Methods: Twenty myasthenia gravis (MG) patients, mean age 44.5 years, were studied. Percutaneous (FR) and intramuscular needle (ED) stimulation approaches were used. Jitter was expressed as the mean consecutive difference (MCD). The filter settings were from 1000 HZ to 10 kHZ . Results: Abnormal MCD was found in 85% for both ED and FR and in 90% when combining the two muscles. An abnormal percentage of outliers was found in 90% for ED and 85% for FR. The mean MCD did not show a difference for ED and FR, but the percentage of outliers and blocking were higher in FR. Abnormality was found in 93.7% (generalized) and in 75% (ocular) of MG cases. For ED outliers abnormality was greater than the MCD. Conclusion: CNE jitter is reliable for investigation of MG, although borderline findings should be judged with caution. Muscle Nerve 2011     

Determining neuromuscular jitter using a monopolar electrode.

Neuromuscular jitter was determined in the extensor digitorum communis (EDC) of 41 healthy control subjects and 8 patients with myasthenia gravis (MG). Standard single-fiber electromyographic (SFEMG) techniques were used, except that a monopolar electrode (MPE) was substituted for a single-fiber electrode (SFE). In normals, mean jitter for 20 pairs was 22.4 +/- 2.8 microseconds and the mean jitter for an individual pair was 22 +/- 5.6 microseconds. In the age range tested (18 to 49 years), jitter did not change with increasing age. When MPE jitter studies were repeated in 16 normals, mean jitter usually varied by less than 10% (mean 7.4% +/- 6.2%) and remained normal. Jitter was significantly increased in MG compared to normals 73 +/- 56 microseconds versus 22 +/- 5.6 microseconds (F = 149.4, P less than 0.0001). Using an analog pain scale, the discomfort during electromyography using MPE and SFE was compared between the left and right arms in 35 normals. MPEs caused less discomfort than SFEs (P = 0.0031), and were preferred (71% versus 20%) to SFEs (chi 2 = 9.21, P = 0.01). Based on these results, we conclude that MPE determined jitter studies are reproducible, can distinguish between normals and MG, and are associated with less discomfort than SFE.     

放射免疫法定量检测乙酰胆碱受体抗体与重症肌无力患者临床特征的相关性

目的探讨乙酰胆碱受体抗体(AChR-Ab)与重症肌无力(MG)临床特征的相关性。方法采用放射免疫法检测115例MG患者及92例对照组(非MG神经系统疾病患者42例,健康体检者50名)血清AChRAb浓度,应用临床绝对评分记录MG患者病情严重程度。分析各组血清AChR-Ab浓度的差异,以及AChR-Ab浓度与MG患者临床特征的相关性。采用ROC工作特征曲线探讨AChR-Ab诊断MG的敏感度和特异度。结果MG患者血清AChR-Ab浓度中位数(四分位数间距,下同)为3.45(39.38)nmol/L,较非MG神经系统疾病患者[0(0)nmol/L]和健康体检者[0(0)nmol/L]增高(P0.01)。全身型MG(GMG)患者AChR-Ab浓度[25.45(46.14)nmol/L]较眼肌型MG(OMG)患者[0.58(3.56)nmol/L]增高(P0.01)。用ROC曲线法分析显示,以血清AChR-Ab浓度≥0.50nmol/L作为诊断MG界值时灵敏度为72.17%,特异度为100%,曲线下面积(AUC)=0.895(95%CI:0.849~0.941)。AChR-Ab浓度与发病年龄、病程及改良Osserman分型呈正相关(r=0.220,P0.05;r=0.184,P0.05;r=0.382,P0.01),但相关性较弱(均r0.5),与临床绝对记分无相关性(r=0.147,P0.05)。结论用放射免疫法检测血清AChR-Ab浓度诊断MG的灵敏度和特异度均高,有助于减少MG的漏诊率及误诊率,值得临床推广。     

Single‐fiber EMG with concentric electrodes in lambert‐eaton myasthenia

Introduction: We analyzed jitter recordings made with concentric needle electrode (CNE) single‐fiber electromyography (SFEMG) in Lambert‐Eaton myasthenia (LEM). Methods: Fifteen subjects diagnosed with LEM were studied using CNE‐SFEMG in the extensor digitorum (ED) and tibialis anterior (TA) muscles. CNE‐SFEMG in the ED and TA was also used to evaluate 12 and 10 healthy controls (HCs), respectively. Results: Ten men and 5 women were diagnosed with LEM based on an increase of 100% in compound muscle action potential amplitude during 50 Hz repetitive nerve stimulation. All patients exhibited markedly greater jitter in the ED (88.8 ± 23.2 µs) and TA (92.2 ± 30.2 µs) than HCs (28.3 ± 3.4 µs and 30.9 ± 5.1 µs, respectively). Conclusions: CNE‐SFEMG is sensitive for discovering abnormalities in neuromuscular transmission in LEM. Muscle Nerve 56 : 253–257, 2017     

Use of stimulated electromyography in the analysis of the neuromuscular junction in children

A screening test is required to diagnose disorders of the neuromuscular junction (NMJ) in children. This Review describes the development of stimulation potential analysis with concentric needle electrodes (SPACE). This nomenclature was chosen to distinguish the technique from single‐fiber methodology because of the difficulties in identifying single‐fiber potentials in most studies, particularly those with the most severe abnormalities of the NMJ. Performed on orbicularis oculi in children with proven or probable disorders of the NMJ, it demonstrated a sensitivity of 84%, specificity of 71%, negative predictive value of 95%, and positive predictive value of 36%. It is well tolerated and within the capability of any clinical neurophysiologist. When combined with a full electrodiagnostic examination, SPACE provides invaluable information about children with NMJ disorders, whose diagnosis often is difficult. Muscle Nerve 56 : 841–847, 2017     

Concentric needle jitter in stimulated frontalis in 20 healthy subjects

Normative data for jitter parameters using a disposable concentric needle have been presented in a few studies. Jitter, expressed as the mean consecutive difference (MCD), was measured in the frontalis muscle in 20 subjects by percutaneous bar stimulation of the temporal nerve branch. The mean MCD for individual studies (20) and for all potentials (600) were 16.05 ± 2.73 μs and 16.05 ± 5.96 μs, respectively. The suggested limit for mean MCD is 22 μs and for outliers is 28 μs.     

乙酰胆碱受体抗体阳性重症肌无力外周血单个核细胞miRNA表达谱

目的本研究对比乙酰胆碱受体抗体阳性重症肌无力患者(AchR-MG)和正常对照组外周血单个核细胞miRNA,预测对AchR-MG发病可能产生影响的通路,为进一步探讨发病机制打下基础。方法采用病例对照研究方法,基于高通量测序,筛选了AchR-MG特异性表达的miRNA。利用TargetScan、miRanda进行靶基因交叉预测,利用基因条目(GO)和京都基因与基因组百科全书(KEGG)进行富集分析。结果共筛选出差异性miRNA 28种,其中上调17种,下调11种。差异最显著的前5个为:mmu-miR-3968、miR-4785、miR-210-3p、miR-664a-3p、miR-2277-5p。miR-4785预测到METTL22、TMEM38A、ZNF324、ITGB4、CDC34等395种靶基因。最终识别了319条GO term(P 0.01),获得了119个的风险通路(P0.05)。结论 AchR-MG特异性表达miR-4785、miR-210-3p、miR-664a-3p、miR-2277-5p等28种miRNA。以Wnt信号通路为代表的多种通路可能参与AchR-MG的发病。     

Concentric needle jitter on voluntary activated frontalis in 20 healthy subjects

Introduction: Normative data for jitter parameters using a disposable concentric needle have been described in a few studies. Methods: Jitter, expressed as the mean consecutive difference (MCD), was measured in the frontalis muscle in 20 subjects by voluntary contraction. Results: Mean MCD for individual studies (20, Gaussian), all potentials (400, non‐Gaussian), and 18th highest value (20, Gaussian) were 19.9 ± 2.9 μs, 19.9 ± 6.6 μs, and 26.9 ± 4.4 μs, respectively. Conclusion: The suggested upper normal limit for mean MCD is 26 μs and for outliers is 36 μs. Muscle Nerve 47:440‐442, 2013     

乙酰胆碱受体抗体阳性重症肌无力外周血单个核细胞miRNA表达谱

目的 本研究对比乙酰胆碱受体抗体阳性重症肌无力患者（AchR-MG）和正常对照组外周血单个核细胞miRNA,预测对AchR-MG发病可能产生影响的通路,为进一步探讨发病机制打下基础。方法 采用病例对照研究方法,基于高通量测序,筛选了AchR-MG特异性表达的miRNA。利用TargetScan、miRanda进行靶基因交叉预测,利用基因条目（GO）和京都基因与基因组百科全书（KEGG）进行富集分析。结果 共筛选出差异性miRNA 28种,其中上调17种,下调11种。差异最显著的前5个为：mmu-miR-3968、miR-4785、miR-210-3p、miR-664a-3p、miR-2277-5p。miR-4785预测到METTL22、TMEM38A、ZNF324、ITGB4、CDC34等395种靶基因。最终识别了319条GO term（P<0.01）,获得了119个的风险通路（P<0.05）。结论 AchR-MG特异性表达miR-4785、miR-210-3p、miR-664a-3p、miR-2277-5p等28种miRNA。以Wnt信号通路为代表的多种通路可能参与AchR-MG的发病。