[Steroid pulse therapy was effective against anti-muscle-specific kinase antibody-positive myasthenia gravis crisis: a case report].

A 50-year-old woman experienced cardiopulmonary arrest. Although the arrest lasted for 4 min, she could not be withdrawn from the mechanical ventilator because of low tidal volume, despite being awake and alert after admission. The results of the anti-acetylcholine receptor antibody and repetitive nerve stimulation tests were negative, and the anti-muscle-specific kinase antibody levels revealed myasthenia gravis. We recommended therapeutic plasma exchange; however, the patient refused the treatment as she did not want to use blood products. Consequently, we initially attempted steroid pulse therapy, which enabled the patient to be withdrawn from the mechanical ventilator. Thus, steroid pulse therapy was beneficial for the crisis associated with the anti-muscle-specific kinase antibody in the absence of therapeutic plasma exchange.

The longest reported sibling survivors of a severe form of congenital myasthenic syndrome with the ALG14 pathogenic variant.

Congenital myasthenic syndromes (CMS) is a group of diseases that causes abnormalities at the neuromuscular junction owing to genetic anomalies. The pathogenic variant in ALG14 results in a severe pathological form of CMS causing end-plate acetylcholine receptor deficiency. Here, we report the cases of two siblings with CMS associated with a novel variant in ALG14. Immediately after birth, they showed hypotonia and multiple joint contractures with low Apgar scores. Ptosis, low-set ears, and high-arched palate were noted. Deep tendon reflexes were symmetrical. They showed worsening swallowing and respiratory problems; hence, nasal feeding and tracheotomy were performed. Cranial magnetic resonance imaging scans revealed delayed myelination and cerebral atrophy. Exome sequencing indicated that the siblings had novel compound heterozygous missense variants, c.590T>G (p.Val197Gly) and c.433G>A (p.Gly145Arg), in exon 4 of ALG14. Repetitive nerve stimulation test showed an abnormal decrease in compound muscle action potential. After treatment with pyridostigmine, the time off the respirator increased. Their epileptic seizures were well controlled by anti-epileptic drugs. Their clinical course is stable even now at the ages of 5 and 2 years, making them the longest reported survivors of a severe form of CMS with the ALG14 variant thus far.

Initial Repetitive Nerve Stimulation Test Predicts Conversion of Ocular Myasthenia Gravis to Generalized Myasthenia Gravis.

BACKGROUND AND PURPOSE: A major concern with ocular myasthenia gravis (MG) is the potential conversion to generalized MG. This study was conducted to determine if the repetitive nerve stimulation (RNS) test could predict the conversion from ocular to generalized MG. METHODS: The RNS test was conducted in a consistent manner on five muscles in the face and limbs in every patient. Subjects were divided into those who remained as ocular MG (ROMG group) and those who experienced conversion to generalized MG during follow-up (GOMG group). RESULTS: Conversion to generalized MG occurred in 24 (21.4%) of 112 MG patients with ocular onset. The proportion of patients displaying abnormal decreases in responses in the trapezius, abductor digiti minimi, or flexor carpi ulnaris muscles on the RNS test was higher in the GOMG group (p<0.001, p=0.002, and p<0.001, respectively). The Cox proportional-hazards model revealed that an abnormal result on the RNS test was significantly associated with conversion to generalized MG [hazard ratio (HR)=3.13, 95% confidence interval (CI)=1.18-8.32]. Notably, the HR was higher for abnormal results on the RNS test for the limb muscles, at 5.19 (95% CI=2.09-12.90). CONCLUSIONS: An abnormal result on the RNS test, especially in the limb muscles, is an independent predictor of the conversion from ocular to generalized MG. Applying the RNS test to limb muscles could be useful for predicting the conversion to generalized MG in patients with ocular onset.

Assessment of the compound muscle action potential amplitude return time between exercises or tests in the repetitive nerve stimulation test for Lambert-Eaton myasthenic syndrome.

INTRODUCTION: When performing postexercise facilitation (PEF) as part of the repetitive nerve stimulation (RNS) test in Lambert-Eaton myasthenic syndrome (LEMS), it is important to avoid any influence of the previous exercise or RNS test on the compound muscle action potential (CMAP) amplitude. METHODS: To measure the CMAP amplitude return time (ART) to that at rest, a single CMAP was obtained every 30 seconds until the amplitude was within 5% of that at rest in three exercise periods (10, 20, and 30 seconds) and in 10-second postexercise (PE) 3-Hz RNS testing with 17 tests in 10 LEMS patients. RESULTS: Adequate ART between tests is 150 seconds for 10-second exercise (Ex) and 10-second PE 3-Hz RNS test, 120 seconds for 20-second Ex, and 90 seconds for 30-second Ex. DISCUSSION: We recommend 150 seconds as adequate ART between the PEF test and the next test when performing RNS test in LEMS.

Repetitive nerve stimulation test in myasthenic crisis.

INTRODUCTION: Herein we report our experience with the repetitive nerve stimulation (RNS) test in myasthenia gravis (MG) crisis. METHODS: The various parameters of the RNS tests in 26 patients with MG crisis were analyzed. RESULTS: In 18 (69%) patients, MG crisis is the first manifestation of MG. RNS tests were abnormal in 24 (92%) patients by decrement at low-rate stimulation in any of 4 tested muscles. Three patterns of abnormality were found: MG pattern (decrement at low-rate stimulation) in 23 patients; Lambert-Eaton myasthenic syndrome pattern in 1 patient; and cholinergic crisis pattern in 1 patient. DISCUSSION: During MG crisis, the RNS test can serve as a rapid and sensitive diagnostic tool for MG in a majority of patients. Muscle Nerve 59:544-544, 2019.

One-minute exercise is best for evaluation of postexercise exhaustion in myasthenia gravis.

INTRODUCTION: To find the best exercise duration for postexercise exhaustion by decrement (PEE-D) in myasthenia gravis (MG). METHODS: In 32 tests in 32 MG patients, repetitive nerve stimulation was performed in the abductor digiti quinti muscle. The 3 Hz responses for 2 s were obtained with supramaximal stimulation at rest, and immediately after (PE0), 30 s after (PE30s), and 1, 2, 3, and 4 min after 10-s, 30-s, and 1-min exercises. RESULTS: Compared with the decrement at rest, a significantly greater decrement was found at PE2m and PE3m after 30-s exercise, and at PE2m, PE3m, and PE4m after 1-min exercise. In 11 patients who showed a decremental response only with exercise, PEE-D was observed in 5 after 30-s exercise and in 8 after 1-min exercise. CONCLUSIONS: One-minute exercise is best for evaluation of PEE-D in MG.

Repetitive nerve stimulation test in amyotrophic lateral sclerosis with predominant oropharyngeal manifestations.

BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis (ALS) patients display easy fatigability and abnormal decrements on repetitive nerve stimulation (RNS) test of clinically involved limb muscles, which can result in ALS being misdiagnosed as myasthenia gravis. We retrospectively analyzed the RNS tests of ten ALS patients with only or predominant oropharyngeal symptoms without ocular or facial weakness. METHODS: RNS tests were performed on the abductor digiti quinti, flexor carpi ulnaris, orbicularis oculi (OO), nasalis and trapezius muscles at low-rate stimulation frequencies of 3 and 5-Hz. Decrements greater than 10% of the compound muscle action potential amplitude on the fifth stimulation compared to the first was regarded as abnormal. RESULTS: Six patients complained of muscular fatigue or diurnal fluctuation. Among the ten patients, three exhibited abnormal decrements during low-rate stimulation in the facial muscles but not in the limb muscles, two exhibited abnormal decrements in the OO and nasalis muscles, and one exhibited abnormal decrements in the OO muscle. CONCLUSIONS: These findings show that the facial muscles may be involved in some early oropharyngeal forms of ALS, although facial weakness may not be clinically evident. We confirm herein that abnormal decrement of facial muscles to RNS test cannot make a definite diagnose for myasthenia gravis.

Repetitive Nerve Stimulation Test in Amyotrophic Lateral Sclerosis with Predominant Oropharyngeal Manifestations

BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis (ALS) patients display easy fatigability and abnormal decrements on repetitive nerve stimulation (RNS) test of clinically involved limb muscles, which can result in ALS being misdiagnosed as myasthenia gravis. We retrospectively analyzed the RNS tests of ten ALS patients with only or predominant oropharyngeal symptoms without ocular or facial weakness. METHODS: RNS tests were performed on the abductor digiti quinti, flexor carpi ulnaris, orbicularis oculi (OO), nasalis and trapezius muscles at low-rate stimulation frequencies of 3 and 5-Hz. Decrements greater than 10% of the compound muscle action potential amplitude on the fifth stimulation compared to the first was regarded as abnormal. RESULTS: Six patients complained of muscular fatigue or diurnal fluctuation. Among the ten patients, three exhibited abnormal decrements during low-rate stimulation in the facial muscles but not in the limb muscles, two exhibited abnormal decrements in the OO and nasalis muscles, and one exhibited abnormal decrements in the OO muscle. CONCLUSIONS: These findings show that the facial muscles may be involved in some early oropharyngeal forms of ALS, although facial weakness may not be clinically evident. We confirm herein that abnormal decrement of facial muscles to RNS test cannot make a definite diagnose for myasthenia gravis.

Iatrogenic Botulism After Intramuscular Injection of Botulinum Toxin Type A

Botulinum toxin type A (BTA) is widely used for both medical treatment and cosmetic purposes. A 46-year-old woman presented with progressive generalized weakness and dysphagia. The patient had injected BTA into her both of her calves by herself for cosmetic purposes. Repetitive nerve stimulation of the right facial nerve demonstrated reduced compound muscle action potential amplitudes of the orbicularis oculi and nasalis muscles, and a reduced response to low-frequency, repetitive stimulation. The possibility of iatrogenic botulism should be considered when using BTA.

Electrophysiological Changes in Lambert-Eaton Myasthenic Syndrome With Intravenous Immunoglobulin Therapy

No abstract available.

Electrophysiologic Responses of Neuromuscular Junction by High Dose of Botulinum Toxin A Injection: Local and Distant Effects

OBJECTIVE: The purpose of this study was to measure the local and distant effects of BTX-A of different dosage through the electrophysiologic study. METHOD: Sixteen Sprague-Dawley rats were used and divided into four groups by the dosage of BTX-A (Botox , Allergan Co.): 2, 4, 6, 8 U for each of the four rats. BTX-A was injected into tibialis anterior (TA) muscles. Slow rate (3 Hz) and fast rate (20 Hz) repetitive nerve stimulation test (RNST) was performed before and after BTX-A injection. The schedule of postinjection was as follows: 2 days after the injection, every seven days till 10 weeks postinjection, once a month for 4 months. RESULTS: In the fast rate RNST of the treated TA muscle, dose-dependent increments were seen on the 2nd day postin jection and thereafter dose-dependent decrements appeared and weakened over the course of time. In the slow rate RNST of the treated TA, dose-dependent decrements were observed through ten weeks postinjection in all groups. In the fast rate RNST of the untreated TA, incremental responses were produced in all groups in a dose-dependent manner. In the slow rate RNST of the untreated TA, there were no changes. CONCLUSION: The BTX-A injection causes local paralysis in the treated muscles and presynaptic dysfunction of the neuro muscular junction in the distant untreated muscles in a dosedependent manner. This study could not be differentiated between neuromuscular dysfunction, myopathy or neuropathy through these RNST studies.

Diagnostic Sensitivity of Several Muscles in Repetitive Nerve Stimulation Test for Myasthenia Gravis / 영남의대학술지

BACKGROUND: This study was undertaken to evaluate the diagnostic sensitivity of several muscles in repetitive nerve stimulation test (RNST) for myasthenia gravis (MG) patients. MATERIALS AND METHODS: The study population consisted of 39 MG patients classified by modified Ossermann's classification. Using Stalberg's method, RNST was systematically performed in facial (orbicularis oculi and nasalis) and upper extremity (flexor carpi ulnaris, abductor digiti quinti and anconeus) muscles. RESULTS: The significant electrodecremental response of RNST were noted in orbicularis oculi (58.9%), nasalis (51.3%), flexor carpi ulnaris (42%), anconeus (41%) and abductor digiti quinti muscles (27%). Among the 3 muscles of upper extremity (abductor digiti quinti, flexor carpi ulnaris and anconeus), the positive electrodecremental response of anconeus muscles was significantly higher than other two muscles (p<0.05) in type IIa, IIb and there were no statistical differences of the positive electrodecremental response between orbicularis oculi and nasalis muscles. The facial muscles showed more prominent decremental responses than upper extremity muscles in type I MG(p<0.05). In type IIa MG patients, there were no significant statistical differences between facial and upper extremity muscles but significant statistical differences among upper extremity muscles. In type IIb MG patients, there were no significant statistical differences in all tested muscles in spite of the increased positive electrodecremental response of RNST. CONCLUSION: On the basis of this study, RNST would be initially performed for the orbicularis or nasalis in type I MG and for the anconeus in type IIa or IIb MG.

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.

Re-evaluation of Repetitive Nerve Stimulation Test in Myasthenia Gravis and Myasthenic Syndrome

BACKGROUND: The repetitive nerve stimulation (RNS) test is a useful tool in the evaluation of neuromuscular transmission disorders. In our laboratory, we frequently use Oh's method, which tests 5 kinds of muscles (flexor carpi ulnaris (FCU), abductor digiti quinti (ADQ), orbicularis oculi, nasalis and trapezius) with 3 kinds of low rate stimulation (LRS) and high rate stimulation (HRS). This method has the advantage of high sensitivity, but is time consuming and painful to patients. So, we tried to reestablish the stage of RNS to overcome this problem and to create a useful test. METHODS: We analyzed RNS data from 369 patients, retrospectively. The number of patients with myasthenia gravis (MG) was 357 and the number with myasthenic syndrome was 12. We compared the sensitivity of individual muscle as well as individual stimulation rate. And we analyzed the results of MG and myasthenic syndrome to verify the usefulness of HRS. RESULTS: The sensitivity of RNS (LRS) was 69.7% in MG (generalized symptom 86.4%, only ocular symptom 40.3%). The sensitivity was higher with 3 pps and 5 pps than with 2 pps, while the exclusion of 2 pps did not affect the sensitivity. We found only 3 cases (1.0%) with post-tetanic exhaustion (PTE) in MG patients with negative results on LRS. The distributions of resting CMAP and post-exercise CMAP were different between MG and myasthenic syndrome. In most cases of myasthenic syndrome, the resting CMAP of ADQ and FCU was below 4.0 mV and post-exercise CMAP of ADQ and FCU was above 50%. CONCLUSIONS: LRS may be done with only 3 and 5 pps, and HRS of the ulnar nerve was helpful only if there was a suspicion of myasthenic syndrome (resting CMAP50%, in ADQ & FCU) or a borderline decremental response in LRS.

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.

Comparison between the Electric and Magnetic Stimulations for a Repetitive Nerve Stimulation Test

The low rate repetitive nerve stimulation test(RST) using the electric stimulation has been known the best procedure among the electroliagnostic evaluations for the neuromuscular transmission. However, the electric stimulation often causes a considerable discomfort and pain during the procedure. On the contrary, the magnetic stimulation is much easier and less painful in activating to activate the deep seated nerves. The purpose of this study was to compare the effect of repetitive magnetic and electric stimulation for the induction of compound muscle action potentials(CMAP) of abductor digiti quinti and deltoid muscles in 25 healthy subjects. The results were showed there were no significant differences in the amplitudes of CMAP of axillary and ulnar nerves between the magnetic and electric stimulations. And there were no significant differences in the decremental ratio of CMAP between the magnetic and electric stimulations. The magnetic stimulations were less painful for the subjects than electric stimulations in both proximal and distal muscles. In conclusion, the magnetic stimulation proved to be a useful method for repetitive nerve stimulations in the diagnosis of neuromuscular disease.

The Effect of Botulinum Toxin Injection on Compound Action Potentials and Repetitive Nerve Stimulation in Rat Gastrocnemius Muscle

Botulinum toxin develops muscular paralysis through the inhibition of acetylcholine release from presynaptic membrane in neuromuscular junction. It has been used clinically to treat strabismus, blepharospasm and spasmodic dysphonia. Recently it was introduced for the treatment of limb spasticity as well. Serial compound muscle action potential(CMAP) amplitudes were measured and repetitive nerve stimulation test(RNST) was performed with 2Hz and 30Hz on the rat gastrocnemius muscle to observe the effect of muscle paralysis. Also, Periodic acid Schiff (PAS) staining sections of the muscle for glycogen was studied to quantify the degree of muscular paralysis. Thirty Sprague-Dawley rats, 10 for control and 20 for experimental group were studied for 12 weeks. Normal saline 0.025 ml and 0.125 ml was injected into gastrocnemius muscle in cotrol group 1 and 2, respectively. Botulinum toxin type A(Botox) was injected 5.0U/0.025 ml in experimental group 1, 2.5U/0.025 ml in group 2, 2.5U/0.125 ml in group 3, and 0.5U/0.025 ml in group 4. The amplitudes of CMAP declined markedly by 81.1% to 96.5% of basal amplitudes on the first week after Botox injection, but slightly recovered on 12th week by 20.8% to 42.2% with greater recovery in lower dose group. RNST with 2Hz produced no remarkable 1 : 5 amplitude change in experimental group. RNST with 30Hz produced marked increment in 1 : 5 amplitude up to 24.4%. PAS staining for muscle sections showed residual glycogen after tetanic stimulation due to neuromuscular block by Botox.