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.     

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.     

Age-related susceptibility to experimental autoimmune myasthenia gravis: Immunological and electrophysiological aspects

Susceptibility to experimental autoimmune myasthenia gravis (EAMG) was found to decrease with aging in both Lewis and Brown Norway (BN) rats. In this study, the difference in susceptibility between young and aged Lewis and BN rats was used to analyze factors determining the clinical severity of EAMG. The incidence and severity of muscular weakness did not correlate with acetylcholine receptor (AChR) loss nor with the ability of antibodies to interfere with AChR function. Aged rats showed significantly lower anti-rat AChR antibody titers than young rats and developed less severe or no clinical signs of disease. In individual young or aged rats, however, no significant correlation was found between the clinical signs of disease and anti-rat AChR titer. Neuromuscular transmission was found to change with aging as measured by single-fiber electromyography (SFEMG). In aged BN rats, increased jitter and blockings were found even before EAMG induction. Despite this disturbed neuromuscular transmission, these aged BN rats were clinically resistant against induction of EAMG. The results of this study indicate that the age-related susceptibility to EAMG is influenced by factors determined by the immune attack as well as mechanisms at the level of the neuromuscular junction. © 1997 John Wiley & Sons, Inc. Muscle Nerve 20: 1091–1101, 1997     

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.     

Engineered agrin attenuates the severity of experimental autoimmune myasthenia gravis

Introduction: Agrin is essential for the formation and maintenance of neuromuscular junctions (NMJs). NT‐1654 is a C‐terminal fragment of mouse neural agrin. In this study, we determined the effects of NT‐1654 on the severity of experimental autoimmune myasthenia gravis (EAMG). Methods: EAMG was induced in female Lewis rats by immunization with the Torpedo acetylcholine receptor (tAChR) and complete Freund's adjuvant (CFA). NT‐1654 was dissolved in phosphate‐buffered saline (PBS) and injected daily subcutaneously into tAChR immunized rats during the first 10 days after immunization, and then every other day for the following 20 days. Results: We showed that NT‐1654 attenuated clinical severity, effectively promoted the clustering of AChRs at NMJs, and alleviated the impairment of NMJ transmission and the reduction of muscle‐specific kinase (MuSK) in EAMG rats. Discussion: We demonstrated that NT‐1654 attenuated clinical severity, effectively promoted the clustering of AChRs at NMJs, and alleviated the impairment of NMJ transmission and the reduction of muscle‐specific kinase (MuSK) in EAMG rats. Muscle Nerve 57 : 814–820, 2018     

Single fiber electromyography in myasthenia gravis during pregnancy

We report the use of single fiber electromyography (SFEMG) to demonstrate changes in the physiologic abnormality of myasthenia gravis (MG) during pregnancy. A 23-year-old became pregnant 15 months after the onset of mild ocular weakness. On initial evaluation, SFEMG jitter measurements demonstrated a slight abnormality of neuromuscular transmission. There was no change in severity of clinical disease or jitter measurements until the third trimester, when she improved. Jitter measurements at that time were normal. Labor was normal and she delivered a normal male. Three days postpartum, myasthenic weakness recurred temporarily and jitter measurements showed worsening. At 16 days and 6 weeks postpartum, she had only minimal medial rectus weakness and jitter studies were normal. Three months postpartum, ocular symptoms recurred and jitter measurements were slightly abnormal. She continued to worsen, developing limb muscle and severe ocular muscle weakness at 4 months postpartum. She was treated with plasma exchange and thymectomy. Prednisone was added 2 months after thymectomy due to continued worsening and development of oropharyngeal weakness. Three years postpartum she was taking prednisone 10 mg every other day and had only slight weakness of neck flexors, and jitter studies were again normal. © 1993 John Wiley & Soncs, Inc.     

Single fiber EMG and repetitive stimulation of the same muscle in myasthenia gravis

We performed RNS and SFEMG studies of the same muscle in 46 patients with myasthenia gravis. Maximum decrement to 3–5-Hz stimulation before and after maximum voluntary exercise, percentage of action potential pairs with increased jitter and blocking, and mean MCD in each study were compared. A significant decrement (> 10% decrease in CMAP area or amplitude between the first and fourth response) was never found without increased jitter and impulse blocking on SFEMG. Increased jitter, blocking, and mean MCD were each correlated with maximum decrement (r > 0.61, P < 0.0001). We conclude that decrement to RNS and impulse blocking on SFEMG result from the same physiologic phenomenon, and that SFEMG is more sensitive at detecting disordered neuromuscular transmission given its ability to detect impulse blocking at levels below the resolution of RNS and increased neuromuscular jitter when there is not blocking. © 1994 John Wiley & Sons, Inc.     

Comparison of diagnosis value for new onset myasthenia gravis by many clinical auxiliary examinations

BACKGROUND: The clinical values of neostigmine test, clinical electrophysiologic study and acetylcholine receptor antibody detection in diagnosing myasthenia gravis (MG) found newly are unclear in China. OBJECTIVE: To investigate the reference value of common clinical diagnosis parameters in correctly diagnosing untreated MG found newly. DESIGN: Retrospective case analysis. SETTING: Department of Neurology, Beijing Hospital, Ministry of Health. PARTICIPANTS: Totally 156 outpatients with MG admitted to Department of Neurology, Beijing Hospital, Ministry of Health between January 1999 and December 2002. The involved patients, 72 males and 84 females, were aged 2–79 years. They were classified according to Osserman's criteria: ⅡA 72，ⅡB 76, Ⅲ 3 and Ⅳ 5. They were all subjected to being inquired of disease history, neostigmine test, and acetylcholine receptor antibody detection, met the diagnosis criteria of Neuroimmunology Committee of China, and confirmed by clinical electrophysiologic detections; Informed consents were obtained from all the involved subjects. METHODS: ①After admission, every patient was intramuscularly injected with 1.5 mg neostigmine; If the patient was a child, the injection dose was decreased according to his/her age. If his/her score of any observation index after injection was improved ≥ 50% as compared with before injection , his positive index was set as positive. Positive neostigmine test was set if there was one positive index. ②Repetitive nerve stimulation and single fiber electromyography were performed with Dantec Keypoint electromyogram (EMG) apparatus. ③Acetylcholine receptor antibody was detected by ELISA method. MAIN OUTCOME MEASURES: Clinical absolute and relative scores of MG, acetylcholine receptor antibody level, and repetitive nerve stimulation and single fiber electromyography examination results. RESULTS: The positive rates of neostigmine test, repetitive nerve stimulation and single fiber electromyography examination for MG were 86.5%, 82.6%, and 69.2%, respectively, and the positive rate of acetylcholine receptor antibody was 78.8%. CONCLUSION: Standardized neostigmine test has the highest sensitivity to diagnose MG.     

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.     

Concentric-needle single-fiber electromyography for the diagnosis of myasthenia gravis

The goal of this study was to estimate the accuracy of concentric-needle single-fiber electromyography (CN-SFEMG) for the diagnosis of myasthenia gravis (MG). A consecutive series of patients referred for CN-SFEMG was evaluated by an investigator blinded to the results of CN-SFEMG in order to determine the presence or absence of MG using an independent reference standard. Sensitivity, specificity, predictive values, and likelihood ratios were calculated. The study population included 51 patients (21 with MG). CN-SFEMG was normal in 34 patients (67%) and abnormal in 17 (33%). The sensitivity of CN-SFEMG for the diagnosis of MG was 0.67 and the specificity was 0.96. The positive likelihood ratio was 16.8 and the negative likelihood ratio was 0.34. The positive and negative predictive values were 0.93 and 0.76, respectively. These results indicate that CN-SFEMG showing abnormal jiggle is extremely useful for confirming the diagnosis of MG, but that CN-SFEMG showing normal jiggle has limited utility in excluding the diagnosis.     

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.     

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.     

重症肌无力患者针电极肌电图肌源性受损表现的临床意义

目的分析重症肌无力(myasthenia gravis,MG)患者针电极肌电图(needle electrode electromyography,NEMG)检查结果的临床意义。方法回顾性分析2011-01-01—2013-12-31期间在解放军第309医院神经内科住院治疗的335例确诊MG患者的NEMG检查结果和临床资料,根据NEMG检查是否出现肌源性受损表现将患者分为两组,对比分析两组患者的临床特点。结果29例(8.7%)NEMG出现肌源性受损表现,异常NEMG均无自发电位,仅表现为运动单位电位(motor unit potential,MUP)波幅降低、时限缩短。NEMG检查有肌源性受损表现组临床绝对评分(20.8±7.3)高于无肌源性受损表现组(14.9±9.0,t=1.79,P0.05)。NEMG检查无肌源性受损表现者多以眼外肌无力为首发症状(85.62%),以肢体和球部肌肉起病者比例较低(14.38%);与无肌源性受损表现者相比,有肌源性受损表现者以眼外肌为首发症状者比例较低(55.17%),多以肢体和球部肌肉受累起病(44.83%),两组差异有统计学意义(χ2=9.79,P0.01)。两组间比较,性别、发病年龄、病程、Osserman分型及胸腺病理类型差异均无统计学意义(均P0.05)。结论 NEMG检测表现为肌源性受损者病情较无肌源性受损表现者重。电生理检查可在一定程度上提示MG病情的严重程度。     

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.     

Diagnostic yield of stimulation and voluntary single-fiber electromyography in myasthenia gravis

Voluntary and stimulation single-fiber electromyography were performed in the extensor digitorum communis muscle of 15 myasthenic patients. The increase in mean and individual mean consecutive difference as well as the proportion of blocking in the volitional activation were greater than in the stimulation method. These differences may be explained in part by the different degree of alteration in large as compared with small motor units in patients with myasthenia gravis. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21:1081–1083, 1998.     

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.     

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.     

Changes in acetylcholinesterase in experimental autoimmune myasthenia gravis and in response to treatment with a specific antisense

Controlled regulation of synaptic nicotinic acetylcholine receptors (AChRs) and acetylcholinesterase (AChE), together with maintenance of a dynamic balance between them, is a requirement for proper function of cholinergic synapses. In the present study we assessed whether pathological changes in AChR perturb this balance, and whether such changes can be corrected. We studied the influence of AChR loss, caused by experimental autoimmune myasthenia gravis (EAMG), on muscle AChE, as well as the reciprocal effect of an antisense targeted towards AChE on both AChR and AChE at the neuromuscular synapse. The extensor digitorum longus (EDL) muscles of EAMG Lewis rats were isolated, and AChE levels and isoform compositions were examined. Although AChE levels in the muscles of healthy and EAMG rats were similar, marked changes were observed in isoform composition. Healthy EDL muscles contained globular (G_1,2, G₄) and asymmetric (primarily A₁₂) isoforms. G_1,2‐AChE was significantly reduced in EAMG muscles, whereas both G₄‐ and A₁₂‐AChE remained unchanged. Treatment of EAMG rats with the antisense EN101 resulted in decreased total muscle AChE, with recovery in G_1,2 and reduction in A₁₂‐AChE. AChE/AChR ratios were determined at the neuromuscular junctions (NMJ). The decrease in AChR levels that occurred as the disease progressed resulted in a dramatic increase in this ratio, and a significant recovery towards normal ratios occurred after EN101 treatment. This improvement was primarily due to increased synaptic AChR content. Our findings emphasise the tight connection between AChR and AChE at the myasthenic NMJ, and the importance of the AChE/AChR ratio in maintaining the required cholinergic balance.     

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     

AAEM minimonograph #25: Single-fiber electromyography

Single-fiber electromyography (SFEMG) is a selective recording technique in which a needle electrode with a small recording surface in the side is used to identify action potentials from individual muscle fibers. The SFEMG parameters of greatest clinical use are fiber density (FD) and neuromuscular jitter. FD reflects the local organization of muscle fibers within the motor unit; jitter reflects the safety factor of neuromuscular transmission at individual neuromuscular junctions. SFEMG can be of great value in demonstrating or excluding abnormalities in mild or questionable disease of nerve, muscle, or the neuromuscular junction. The neuromuscular jitter may be measured during nerve stimulation, which is particularly useful in uncooperative patients or when it is desirable to control the firing rate precisely, or during voluntary muscle activation, which is less subject to technical artifact. The SFEMG findings may not be specific to a particular diseases, but they frequently increase understanding of the disease process by demonstrating abnormal neuromuscular transmission or rearrangement of muscle fibers within the motor unit, which complements information from more conventional EMG examinations. © 1996 American Association of Electrodiagnostic Medicine. Published by John Wiley & Sons, Inc.