Electrophysiological evaluation of the neuromuscular junction: a brief review / Avaliação eletrofisiológica da junção neuromuscular: breve revisão

Abstract The nerve terminal and muscle membrane compose the neuromuscular junction. After opening the voltage-gated calcium channels, action potentials from the motor axons provoke a cascade for the acetylcholine release from synaptic vesicles to the synaptic cleft, where it binds to its receptor at the muscle membrane for depolarization. Low amplitude compound muscle action potential typically presents in presynaptic disorders, increasing by more than 100% after a 10-second effort in the Lambert-Eaton myasthenic syndrome and less in botulism. Needle electromyography may show myopathic motor unit action potentials and morphological instability ("jiggle") due to impulse blocking. Low-frequency repetitive nerve stimulation (RNS) is helpful in postsynaptic disorders, such as myasthenia gravis and most congenital myasthenic syndromes, where the number of functioning acetylcholine receptors is reduced. Low-frequency RNS with a decrement >10% is abnormal when comparing the 4th to the first compound muscle action potential amplitude. High-frequency RNS is helpful in presynaptic disorders like Lambert-Eaton myasthenic syndrome, botulism, and some rare congenital myasthenic syndromes. The high-frequency RNS releases more calcium, increasing the acetylcholine with a compound muscle action potential increment. Concentric needle records apparent single-fiber action potentials (spikes). A voluntary activation measures the jitter between spikes from two endplates. An electrical activation measures the jitter of one spike (one endplate). The jitter is the most sensitive test for detecting a neuromuscular junction dysfunction. Most neuromuscular junction disorders are responsive to treatment.

Resumo O nervo terminal e a membrana muscular compõem a junção neuromuscular. Após a abertura dos canais de cálcio dependentes de voltagem, os potenciais de ação do axônio motor provocam uma cascata de eventos que libera acetilcolina das vesículas para a fenda sináptica, ligando-se ao receptor na membrana muscular para despolarização. O potencial de ação muscular composto de baixa amplitude ocorre nas desordens pré-sinápticas, aumentando em mais de 100% após esforço de 10 segundos na síndrome miastênica de Lambert-Eaton e menos no botulismo. A eletromiografia pode mostrar potenciais de ação da unidade motora miopáticos e instabilidade morfológica ("jiggle") devido ao bloqueio do impulso. Estimulação nervosa repetitiva (ENR) de baixa frequência é útil nos distúrbios pós-sinápticos, como miastenia gravis e a maioria das síndromes miastênicas congênitas, quando há número reduzido de receptores de acetilcolina funcionantes. ENR de baixa frequência com decremento >10% é anormal comparando-se à amplitude do quarto com o primeiro potencial de ação muscular composto. ENR de alta frequência é útil nas doenças pré-sinápticas, como síndrome miastênica de Lambert-Eaton, botulismo e algumas síndromes miastênicas congênitas raras. ENR de alta frequência libera mais cálcio, aumenta acetilcolina, resultando em incremento do potencial de ação muscular composto. O eletrodo de agulha concêntrico registra potenciais de ação aparente de fibra única (PAAFU). Ativação voluntária mede jitter entre dois PAAFUs (duas junções neuromusculares). Ativação elétrica mede jitter de um PAAFU (uma junção neuromuscular). Jitter é o teste mais sensível para detectar disfunção de junção neuromuscular. A maioria dos distúrbios juncionais é responsiva ao tratamento.

Stimulation single fiber electromyography in orbicularis oculi in ocular myasthenia gravis / 中华神经科杂志

Objective:To establish the reference values of stimulation single fiber electromyography (SFEMG) in orbicularis oculi, and to explore its sensitivity in repetitive nerve stimulation (RNS) negative ocular myasthenia gravis (OMG) patients, and the relationship between jitter and various clinical parameters.Methods:Thirty-two healthy volunteers were included to establish the reference value of normal controls from January 2019 to December 2019. From December 2019 to January 2023, 36 OMG patients with negative RNS were collected. Quantitative MG score (QMGS) was performed, neostigmine test and antibody titers as well as thymus CT results were recorded. One side of the orbicularis oculi muscle was tested with a disposable concentric needle electrode in stimulation SFEMG, and the mean consecutive difference (MCD) value was calculated, which was compared with the average MCD value and upper limit of individual values in normal controls to evaluate whether the jitter was abnormal. Spearman correlation analysis of abnormal mean MCD values with QMGS and antibody titer was conducted.Results:Among the 32 healthy volunteers, there were 13 males and 19 females, the age was (46.8 ±18.7) years, and the MCD was (19.0 ±4.4) μs. The upper limit of the reference value was 27.7 μs for average MCD, and 37.4 μs for 10% individual values. Among 36 OMG patients negative at RNS tests, 20 were male and 16 were female, with a age of (37.2 ±17.0) years. The MCD was (29.9 ±14.7) μs, and Jitter was abnormal in 29 patients (81%). Among them, 20 (20/25) patients were antibody positive, 6 (6/26) patients had thymic hyperplasia, and 7 (7/26) patients had thymoma. The QMGS was 3(2, 4). There were 7 patients (19%) with normal jitter, whose QMGS was 3(2, 4). Among the patients with normal Jitter, 5 (5/5) patients were antibody positive, 2 (2/6) patients had thymic hyperplasia. There was no statistically significant difference in clinical indicators between the two groups of patients with abnormal or normal jitter. There was no significant correlation in antibody titer or QMGS with abnormal mean MCD value. Conclusions:The upper limit of the mean MCD value in the normal controls is 27.7 μs. The upper limit of a single value is 37.4 μs. Its sensitivity for OMG patients with RNS negative is 81%, and the abnormal mean MCD value does not show a significant correlation with various clinical indicators. Abnormal jitter indicates dysfunction of neuromuscular junction transmission, which is an important neuroelectrophysiological indicator for MG patients and is suitable for RNS negative patients. Orbicularis oculi muscle stimulation SFEMG provides a reliable and sensitive electrophysiological means for functional evaluation of neuromuscular junction.

Acupuncture combined with western medication for ocular myasthenia gravis: a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the clinical efficacy between acupuncture combined with western medication and simple western medication for ocular myasthenia gravis (OMG), and to explore its possible mechanism.@*METHODS@#A total of 60 patients of ocular myasthenia gravis were randomized into an acupuncture combined with western medication group (30 cases, 1 case dropped off) and a western medication group (30 cases, 2 cases dropped off). Oral pyridostigmine bromide tablet and prednisone acetate tablet were given in the western medication group. On the basis of the treatment in the western medication group, Tongdu Tiaoqi acupuncture (acupuncture for unblocking the governor vessel and regulating qi ) was applied at Baihui (GV 20), Fengfu (GV 16), Hegu (LI 4), Zusanli (ST 36), etc. in the acupuncture combined with western medication group, once a day, 6 days a week. The treatment was given 8 weeks in both groups. Before and after treatment, the OMG clinical absolute score was observed, electrophysiological indexes of orbicularis oculi (value of mean jitter, percentage of jitter >55 μs and percentage of blocks) were measured by single-fiber electromyography (SFEMG), serum levels of acetylcholine receptor antibody (AChR-Ab), interferon-gamma (IFN-γ) and interleukin-4 (IL-4) were detected by ELISA method.@*RESULTS@#After treatment, the OMG clinical absolute scores, values of mean jitter, percentages of jitter >55 μs, percentages of blocks and serum levels of AChR-Ab, IFN-γ and IL-4 were decreased compared before treatment in both groups (P<0.05), and those in the acupuncture combined with western medication group were lower than the western medication group (P<0.05).@*CONCLUSION@#Acupuncture combined with western medication can effectively improve ptosis, palpebra superior fatigability, eye movement disorder and neuromuscular junction dysfunction in patients with ocular myasthenia gravis, the therapeutic effect is superior to simple western medication. Its mechanism may be related to down-regulating serum levels of AChR-Ab, IFN-γ and IL-4 and promoting the recovery of orbicularis oculi function.

Utility of single fiber electromyography in the differential diagnosis of hyperthyroidism associated with ocular myasthenia gravis and Graves ophthalmopathy / 临床神经病学杂志

Objective To assess the utility of single fiber EMG (SFEMG)in the differential diagnosis of hyperthyroidism associated with ocular myasthenia gravis (OMG)and Graves ophthalmopathy.Methods SFEMG was performed in orbicularis oculi muscle of 2 groups of patients.including 32 patients with hyperthyroidism associated with OMG,and 35 patients with Graves ophthalmopathy.The parameters of SFEMG between different groups were compared.Results The mean jitter was (96.2 ± 23.7),(42.8 ± 12.6)μs in hyperthyroidism associated with OMG and patients with Graves Orbitopathy. M50of the percentage of jitter ＞55 μs was 92% and 5% in the 2 groups respectively.M50of the percentage of block was 25% and 0 in the 2 groups respectively.Fiber density was (1.9 ± 0.4)and (1.7 ± 0.5)in the 2 groups respectively.There was significant difference in those parameters of SFEMG between the patients in 2 groups(t＝15.56,Z＝9.26,Z＝7.35,all P＜0.01).Conclusion SFEMG of orbicularis oculi muscle shows significantly increased jitter and block in hyperthyroidism associated with OMG,which can help to differentiate hyperthyroidism associated with OMG from Graves ophthalmopathy.

Stimulated jitter with concentric needle in 42 myasthenia gravis patients / Jitter estimulado obtido com agulha concêntrica em 42 pacientes com miastenia gravis

Objective: To estimate jitter parameters in myasthenia gravis in stimulated frontalis and extensor digitorum muscles using the concentric needle electrode. Methods: Forty-two confirmed myasthenia gravis patients, being 22 males (aged 45.6±17.2 years-old) were studied. Jitter was expressed as the mean consecutive difference (MCD). Results: MCD in extensor digitorum was 61.6 µs (abnormal in 85.7%) and in frontalis 57.3 µs (abnormal in 88.1%). Outliers represented 90.5% for extensor digitorum and 88.1% for frontalis. At least one jitter parameter was abnormal in 90.5% of the combined studies. Acetylcholine receptor antibody was abnormal in 85.7% of the cases. Conclusions: Stimulated jitter recordings measured from muscles using concentric needle electrode can be used for myasthenia gravis diagnosis with high sensitivity. Extensive normative studies are still lacking and, therefore, borderline findings should be judged with great caution. .

Objetivo: Mensurar os valores do jitter em pacientes com miastenia gravis nos músculos frontalis e extensor digitorum pela técnica estimulada, utilizando-se eletrodo de agulha concêntrica. Métodos: Foram estudados 42 pacientes, sendo 22 homens (idade 45,6±17,2 anos), com miastenia gravis confirmada. O jitter foi expresso como a média das diferenças consecutivas (MDC). Resultados: A MDC para o extensor digitorum foi 61,6 µs (anormal em 85,7%) e para o frontalis 57,3 µs (anormal em 88,1%). Outliers representaram 90,5% para o extensor digitorum e 88,1% para o frontalis. Pelo menos um parâmetro do jitter foi anormal em 90,5% dos estudos combinados. Anticorpo receptor de acetilcolina estava anormal em 85,7% dos casos. Conclusões: Jitter estimulado mensurado por meio de eletrodo de agulha concêntrica pode ser utilizado para diagnóstico de miastenia gravis com elevada sensibilidade. Estudos normativos mais amplos ainda são necessários e, portanto, valores limítrofes devem ser avaliados com cautela. .

A study of the terminal sprouting after intramuscular injection of Botulinum toxin type A / 中华物理医学与康复杂志

Objective To investigate the pathological and electro-physiological process of terminal sprouting after muscle injection of Botulinum toxin type A(BTXA) in rats. Methods Sprague-Dawley rats were randomly divided into a BTXA group and a control group. Five unit of BTXA was injected into the right gastrocnemius of the rats in BTXA group, instead of 0.9% saline in the control group. The morphologic axon analysis and SFEMG (mean consecutive difference and fiber density) were measured at 1,4,8,12 week after injection. Results The mean consecutive difference was prolonged in 1-4 week, and got better at 8 week, recovered at 12 week. It was revealed of the recovery of neuromuscular junction at 12 week after BTXA injection. The results of fiber density and morphologic axon analysis demonstrated terminal sprouting after injection of BTXA. Conclusion Motor nerve terminal sprouting could appear after BTXA injection and the function of neuromuscular junction could become recovered at 12 week.

A comparative study of single fiber electromyography and repetitive nerve stimulation of the same extensor digitorum communis muscle in patients with myasthenia gravis / 中华物理医学与康复杂志

Objective To investigate the possible causes of the different diagnostic sensitivity of voluntary single fiber electromyography (SFEMG) and repetitive nerve stimulation(RNS) in patients with myasthenia gravis (MG). Methods The voluntary SFEMG and RNS at low rates were recorded successively from the same extensor digitorum communis (EDC) muscle on the same day in 67 patients with MG. Results The diagnostic sensitivity of SFEMG and RNS was 92.5% and 50.7%, respectively, with the former statistically significantly higher than the later. The percentage of decrement of RNS was positively correlated with 3 SFEMG parameters, i.e. the mean jitter, percentage of abnormal pairs of potential and percentage of impulse blocking. Among the 34 cases with significant decrement on RNS, 2 had no impulse blocking and the maximum decrement reached 62%, while 33 cases with normal RNS had up to 58% of impulse blocking. Conclusion The voluntary SFEMG was more sensitive than RNS in diagnosing MG even in the same muscle. The blocking phenomenon observed in voluntary SFEMG was not completely corresponding to the decrement in RNS.The possible explanations were partly because that RNS recorded the total muscle fibers response in surface of the muscle and SFEMG examined the increasing or blocking at individual motor end-plates, and partly because that the voluntary SFEMG and RNS might explored endplates belonging to different motor units.

Sensitivity of Diagnostic Tests and Therapeutic Outcome in Ocular Myasthenia Gravis

PURPOSE: To compare the sensitivity of various diagnostic tests, and to assess the efficacy of therapy in the management of myasthenia gravis (MG). METHODS: Thirty-two patients with ocular findings with MG were examined by Stimulated Single Fiber Electromyograhy (SFEMG), Repetitive Nerve Stimulation (RNS) test, Edrophonium (Tensilon) test, anti-acethylcholine receptor antibody titer. We also studied retrospectively clinical characteristics and efficacy RESULTS: Mean age of patients was 32 years (range 1 to 63 years). Twenty (62.5%) were females and 12 (37.5%) were males. Mean duration of symptoms was 17 months (range 5 months to 10 years). Associated ocular findings were ptosis 31 eyes (97%), diplopia 20 eyes (63%), and ocular limitation 19 eyes (59%). The value of diagnostic sensitivity was 97% in SFEMG, 94% in tensilon test, 75% in RNS test, and 69% in anti-acetylcholine receptor antibody assay. Nine of 10 cases who were treated with thymectomy and pyridostigmine were markedly improved. Eight cases (25%) subsequently developed generalized type of myasthenia gravis. CONCLUSIONS: Ptosis and diplopia were most frequently associated with ocular myasthenia gravis. For diagnosis of ocular myasthenia gravis, SFEMG or tensilon test was the most sensitive test. Thymectomy combined with pyridostigmine bromide seemed to be an effective therapeutic modality.

Diagnostic value of single fiber electromyography in diabetic peripheral neuropathy / 临床神经病学杂志

Objective To study the diagnostic value of single fiber electromyography (SFEMG) in diabetic peripheral neuropathy (DPN).Methods The values of jitter and fiber density (FD) in 36 patients with diabetes mellitus of 2 type were determined by Viking Ⅳ, while conventional nerve conduction studies (NCS) were performed,and the fasting blood glucose and glycosylated hemoglobin A 1C (HbA 1C ) were measured.Results The values of jitter were associated with FD, and both jitter and FD were positively related to HbA 1C .18 cases with abnormal NCS showed increased jitter(11 cases with block),and increased FD in 14 cases; the remaining 18 cases with normal NCS,7 cases with increased jitter(3 cases with block),the increased FD in 5 cases.Conclusion Denervation reinnervation reflected by jitter and FD was associated with the metabolic status. SFEMG could be served as sensitive means to early diagnosis of DPN, and might detect subclinical peripheral neuropathy of diabetes.

Clinical Significance of Axonal Stimulation Single Fiber Electromyography in Patients with Myasthenia Gravis

BACKGROUND: The axonal stimulation single fiber electromyography (S-SFEMG) is a relatively new electrophysio-logical technique and has several advantages over conventional voluntarily activated single fiber electromyography (V-SFEMG). This study was performed in patients with myasthenia gravis (MG) in order to analyze their neuromuscular transmission defects and thus to verify the usefulness of the S-SFEMG technique. METHODS: In 44 patients with MG, S-SFEMG was performed on the extensor digitorum communis muscle. The repetitive nerve stimulation test (RNST) on orbicularis oculi, trapezius, flexor carpi ulnaris, and abductor digiti quinti muscles was also performed at the same time. The results of the RNS and S-SFEMG were then analysed in detail. RESULTS: The S-SFEMG was found abnormal in 84.1%, while RNST was found abnormal in 75.0% of the patients tested. The normal S-SFEMG result was observed exclusively among 7 ocular type MG patients. The mean of the mean consecutive difference (MCD) value, % of fibers with blocking and % of fibers with abnormal jitter, was more increased in patients with generalized type MG than those with ocular type MG. This difference was statistically significant (P<0.01) in all 3 variables. CONCLUSIONS The S-SFEMG is a highly sensitive and useful diagnostic tool in MG. Although it demands more strict technical consideration than V-SFEMG, it is less time-consuming and applicable to uncooperative patients including children. Our study shows S-SFEMG to be especially useful in patients with ocular type MG whose RNST results do not show definite decremen-tal responses.

Correlations between electrophysiological parameters of repetitive nerve stimulation and single fiber electromyography tests in myasthenia gravis

BACKGROUND AND PURPOSE: For diagnosis of acquired autoimmune myasthenia gravis (MG), single fiber electromyography (SFEMG) is known to be much more sensitive than repetitive nerve stimulation test (RNST) in demonstrating the electrophysiological defects of neuromuscular transmission. Neuromuscular blocking in SFEMG is presumed to have the same physiologic basis with decremental response in RNST. The authors performed the study to know the correlations between the electrophysiological parameters of the RNST (decremental response) and the SFEMG (jitter and blocking) and to understand the basic physiological mechanisms in MG. METHODS: In 28 patients with definite MG (12 : ocular MG, 16 : generalized MG), RNST and SFEMG tests were done in orbicularis oculi and abductor digiti quinti and in extensor digitorum communis, respectively. The correlations between several factors, such as maximum decremental response (%) in RNST, mean value of mean consecutive differences (MCD's) (?sec) and blocking pairs (%) were analyzed. RESULTS: In 12 ocular MG patients, RNST and SFEMG abnormalities were found in 4 (33.3%) and in 10 (83.3%), respectively. In 16 generalized MG patients, abnormal decremental responses were found in 13 (81.3%) and increased jitters in 15 (93.8%). SFEMG showed significant correlations between blockings and mean MCD's (R=0.54, p<0.01). When the correlation between RNST and SFEMG was analyzed, increased percentage of blockings in extensor digitorum communis were correlated with maximum degree of decremental responses in abductor digiti quinti or orbicularis oculi (R=0.60, p<0.001). The degree of mean MCD's was poorly correlated with maximum decremental responses (R=0.23, p=0.229). But the correlation became significant (R=0.43, p<0.05) by analyzing mean MCD's and maximum decremental responses only from abductor digiti quinti, reflecting that blockings have similar electrophysiological meanings with increased mean MCD's. CONCLUSION: The good correlation between decremental response in RNST and blocking or mean MCD's in SFEMG was found. Therefore the authors concluded that the parameters of the RNST and the SFEMG show similar electrophysiologic phenomena of the abnormal neuromuscular transmission in MG.