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JTO Clinical and Research Reports Nov 2022Immune checkpoint inhibitors including atezolizumab and durvalumab have been approved as the first-line treatment in extensive-stage SCLC. However, immune checkpoint...
Immune checkpoint inhibitors including atezolizumab and durvalumab have been approved as the first-line treatment in extensive-stage SCLC. However, immune checkpoint inhibitors can cause immune-related adverse events, which will lead to the shelving of follow-up treatment and the progression and deterioration of SCLC. Myasthenia gravis (MG) is a relatively rare and fatal presentation of immune-related adverse events, and experience with immune-related MG in patients with SCLC is limited. Herein we present a patient who developed generalized MG after receiving three cycles of treatment with etoposide, carboplatin, and atezolizumab. Immune-related MG was identified, with pyridostigmine bromide, intravenous immunoglobulin, and glucocorticoids given in time. Fortunately, the patient's MG was relieved, and treatment of SCLC was restarted subsequently.
PubMed: 36246044
DOI: 10.1016/j.jtocrr.2022.100354 -
Neuromuscular Disorders : NMD Oct 2022Pyridostigmine is the most commonly used drug in the symptomatic treatment of myasthenia gravis (MG); however, research into its effectiveness and side effects is...
Pyridostigmine is the most commonly used drug in the symptomatic treatment of myasthenia gravis (MG); however, research into its effectiveness and side effects is scarce. The aim of this study was to assess the effectiveness, prevalence of side effects and net benefit of pyridostigmine. All MG patients participating in the Dutch-Belgian myasthenia patient registry were included. A dynamic online questionnaire was developed to assess the effectiveness, side effects and net benefit of pyridostigmine. Out of 642 invited patients, 410 patients (64%) fully completed the questionnaire; 61% reported that they currently used pyridostigmine, 36% had discontinued pyridostigmine and 2% reported to never have used pyridostigmine. Patients reported a median effectiveness of 60, IQR 28-78 and net benefit of 65, IQR 45-84. Of all patients currently using pyridostigmine, 91% reported side effects (vs. 55% in the control group). Most frequently reported side effects were flatulence, urinary urgency, muscle cramps, blurred vision and hyperhidrosis. In the group of patients who discontinued pyridostigmine, side effects were the reason for discontinuation in 26%. Diarrhea, abdominal cramps and muscle twitching were the most frequently cited reasons to discontinue pyridostigmine. These results can be used to guide shared decision making prior to starting symptomatic treatment for MG.
Topics: Humans; Pyridostigmine Bromide; Cross-Sectional Studies; Myasthenia Gravis; Muscle Weakness
PubMed: 36184373
DOI: 10.1016/j.nmd.2022.09.002 -
Journal of Biomolecular Structure &... 2023Nerve agent poisoning is still a threat to civilization. Nerve agents function by binding with the enzyme acetylcholinesterase irreversibly. Accumulation of...
Nerve agent poisoning is still a threat to civilization. Nerve agents function by binding with the enzyme acetylcholinesterase irreversibly. Accumulation of acetylcholine in the synapse causes over-stimulation of muscarinic and nicotinic acetylcholinergic receptors. Thus miosis, glandular hyper secretion, bronchoconstriction, vomiting, diarrhea and bradycardia occurs (by M1-M5 receptors stimulation); whereas convulsion and seizures occur due to the nicotinic receptors. Atropine is a non-selective muscarinic antagonists but no nicotinic antagonists are known. Seizures are controlled by diazepam. Enzyme aging occurs without treatment which causes the enzyme resistant to oxime therapy. Though numerous wet-lab based works has carried out, however, recent time there is an over-growing trend to make comparative assessment of drugs and toxicants. Here we made a molecular docking based comparative assessments between nerve agents toxicity and efficacy of different drugs to prevent this toxicity. Our results suggest that VX is the most harmful organophosphate nerve agents and HI-6 is the best drug followed by Obidoxime and Pralidoxime to free acetylcholinestarase. Docking results correspond the data trend of different experiments for the assessment of severity of different nerve agents and/or effectiveness of different antidote drugs. Our study reinforces the utility of pretreatment of the enzyme with a carbamic acid derivative like Pyridostigmine bromide which inhibits the enzyme reversibly to a smaller extent and thus, prevent the enzyme from aging and the nerve agent binding.Communicated by Ramaswamy H. Sarma.
PubMed: 36152998
DOI: 10.1080/07391102.2022.2125904 -
BMJ Case Reports Sep 2022We present a case of pyridostigmine-induced coronary artery spasm in a woman with early-onset myasthenia gravis (MG) who suffered from acute chest discomfort a few days...
We present a case of pyridostigmine-induced coronary artery spasm in a woman with early-onset myasthenia gravis (MG) who suffered from acute chest discomfort a few days after pyridostigmine dose up-titration. Twelve-lead ECG demonstrated ST-segment elevation in inferior limb leads together with sinus arrest. Sublingual nitrate was immediately given, which rapidly relieved her symptoms concomitantly with the resolution of abnormal ECG findings. Coronary angiography showed normal coronary arteries reflecting the transient nature of the disease. A small dose of pyridostigmine was rechallenged under close monitoring in the coronary care unit and reproduced her chest discomfort. After the substitution of pyridostigmine with immunosuppressive agents and prescription of long-acting nitrate, she had no recurrence of chest discomfort, as well as well-controlled MG symptoms.
Topics: Coronary Vasospasm; Coronary Vessels; Female; Humans; Myasthenia Gravis; Nitrates; Pyridostigmine Bromide; Spasm
PubMed: 36104035
DOI: 10.1136/bcr-2022-249819 -
Journal of Traditional Chinese Medicine... Oct 2022To investigate the clinical efficacy of Fufang Huangqi decoction in combination with pyridostigmine bromide tablets, prednisone, and tacrolimus in the treatment of type...
Effect of treatment with Fufang Huangqi decoction on dose reductions and discontinuation of pyridostigmine bromide tablets, prednisone, and tacrolimus in patients with type I or II myasthenia gravis.
OBJECTIVE
To investigate the clinical efficacy of Fufang Huangqi decoction in combination with pyridostigmine bromide tablets, prednisone, and tacrolimus in the treatment of type I and II myasthenia gravis (MG) through changes in the clinical symptom scores of 100 patients with type I and II MG. This study also aimed to examine dose reductions and dis-continuation of these 3 Western medicines after administration of Fufang Huangqi decoction.
METHODS
The clinical data on 100 patients with type I or II MG who were treated in the outpatient department of the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, China, between June 2017 and June 2020 were collected. The patients were divided into 4 groups based on whether they had taken pyridostigmine bromide tablets, prednisone, and/or tacrolimus at the time of their hospital visit: the Fufang Huangqi decoction group (group A), the pyridostigmine bromide tablets + Fufang Huangqi decoction group (group B), the pyridostigmine bromide tablets + prednisone + Fufang Huangqi decoction group (group C), and the pyridostigmine bromide tablets + tacrolimus + Fufang Huangqi decoction group (group D). The average treatment time was (15.6 ± 11.5) months (range: 0.5-55 months). Changes in the clinical symptom scores of the 4 groups of patients after medication administration and dose reductions and discontinuation of the 3 Western medicines were analyzed.
RESULTS
An overall effectiveness rate of 86.00% was achieved in the 100 patients after treatment for (15.6 ± 11.5) months (range 0.5-55 months). The effectiveness rates were 85.71% in group A, 88.24% in group B, 76.92% in group C, and 80.00% in group D. The dosage of pyridostigmine bromide was reduced for 69.12% of the patients in group B for the first time after (4.2 ± 4.1) months, and 45.59% of the patients in group B discontinued pyridostigmine bromide after (8.8 ± 6.1) months. The dosage of pyridostigmine bromide was reduced for 46.15% of the patients in group C for the first time after (5.3 ± 3.4) months, and 23.08% of the patients in group C discontinued pyridostigmine bromide after (19.8 ± 11.0) months; 76.92% reduced hormone dosage after (2.8 ± 1.9) months, and 23.08% discontinued hormone treatment after (6.7 ± 2.9) months. The dosage of pyridostigmine bromide was reduced for 1 patient in group D after 1 month; this patient discontinued pyridostigmine bromide after 3 months and reduced tacrolimus dosage after 5 months. One patient in group D discontinued pyridostigmine bromide and tacrolimus on his own initiative at 0.5 months and took Fufang Huangqi decoction for 2 months without discontinuing Western medicine.
CONCLUSION
Fufang Huangqi decoction is effective for the treatment of type I and II MG and improves the associated clinical symptoms. Moreover, this agent is conducive to dose reductions and discontinuation of basic Western medicines, thereby reducing the side effects experienced by patients.
Topics: Drug Tapering; Drugs, Chinese Herbal; Hormones; Humans; Myasthenia Gravis; Prednisone; Pyridostigmine Bromide; Tablets; Tacrolimus
PubMed: 36083490
DOI: 10.19852/j.cnki.jtcm.20220719.004 -
The Journal of International Medical... Jul 2022Myasthenia gravis (MG) is an acquired autoimmune disease. Its clinical manifestations comprise ptosis, diplopia, dysarthria, dysphagia, limb weakness, and in severe... (Review)
Review
Myasthenia gravis (MG) is an acquired autoimmune disease. Its clinical manifestations comprise ptosis, diplopia, dysarthria, dysphagia, limb weakness, and in severe cases, respiratory muscle involvement. Dysarthria as an exclusive initial and primary complaint in MG is rare and seldom reported. In this paper, we report a case of type IIIb MG with isolated dysarthria as the only clinical manifestation and we review the relevant literature. The patient was a 62-year-old man who presented with episodes of slurred speech for 20 days that had worsened in the previous 9 days. His medical history comprised hypertension, diabetes mellitus, and coronary heart disease. The initial diagnosis on admission was transient ischemic attack. Careful re-examination of the patient's history revealed that his symptoms mainly involved increasingly worse slurred speech episodes without drinking or swallowing difficulties, and no significant improvement with rest was observed. Electromyography and autoantibody profiling led to a diagnosis of type IIIb MG. His symptoms improved after the oral administration of pyridostigmine bromide 60 mg. Laryngeal MG is important to differentiate from stroke. It is necessary to perform a computerized voice analysis when encountering patients with atypical symptoms of MG.
Topics: Blepharoptosis; Deglutition Disorders; Dysarthria; Humans; Male; Middle Aged; Myasthenia Gravis; Pyridostigmine Bromide
PubMed: 35915860
DOI: 10.1177/03000605221109395 -
Child's Nervous System : ChNS :... Oct 2022Achondroplasia is the commonest skeletal dysplasia of autosomal dominant inheritance caused by "gain of function" mutations in the fibroblast growth factor receptor 3... (Review)
Review
BACKGROUND
Achondroplasia is the commonest skeletal dysplasia of autosomal dominant inheritance caused by "gain of function" mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. Foramen magnum compression due to accelerated ossification and spinal canal stenosis secondary to reduced interpedicular distance is a hallmark of achondroplasia, driven by G380R nucleotide pair substitution. In severe cases, limb weakness and neurogenic claudication will require surgical decompression. Rarely, a neurological condition may mimic the compressive spinal dysfunction and therefore, non-surgical causes must also be considered in cases of acute neurological deterioration in children with achondroplasia. Myasthenia gravis (MG) is an autoimmune condition resulting in fatigable muscle weakness. There are no reported cases of myasthenia gravis in achondroplasia in the literature.
RESULTS
We report a child with achondroplasia scheduled for decompressive surgery for severe lumbar canal stenosis presenting with neurological claudication and knee weakness. While waiting for surgery during the COVID-19 pandemic, she developed generalized fatigability and severe weakness raising concerns of acute worsening of cord compression. Urgent investigations ruled out spinal cord compression but identified an unexpected concurrent myasthenia gravis with positive antibodies to acetylcholine receptors. The surgical intervention was postponed averting the potential risk of life-threatening anaesthetic complications. She was successfully managed with a combination of pyridostigmine, steroids, azathioprine, and plasma exchange.
CONCLUSION
We report the first case of myasthenia gravis in achondroplasia and review implications in the management.
Topics: Achondroplasia; Anesthetics; Azathioprine; COVID-19; Child; Constriction, Pathologic; Female; Humans; Myasthenia Gravis; Nucleotides; Pandemics; Pyridostigmine Bromide; Receptor, Fibroblast Growth Factor, Type 3; Receptors, Cholinergic; Spinal Cord Compression
PubMed: 35908138
DOI: 10.1007/s00381-022-05617-1 -
Zhongguo Zhen Jiu = Chinese Acupuncture... Jul 2022To compare the clinical efficacy between acupuncture combined with western medication and simple western medication for ocular myasthenia gravis (OMG), and to explore... (Randomized Controlled Trial)
Randomized Controlled Trial
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, acupuncture (acupuncture for unblocking the governor vessel and regulating ) 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 (<0.05), and those in the acupuncture combined with western medication group were lower than the western medication group (<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.
Topics: Acupuncture Therapy; Facial Muscles; Humans; Interferon-gamma; Interleukin-4; Myasthenia Gravis
PubMed: 35793884
DOI: 10.13703/j.0255-2930.20210908-k0003 -
Muscle & Nerve Oct 2022We studied the progression of myasthenia gravis (MG) disease burden and medication adjustment among MG Patient Registry participants.
INTRODUCTION/AIMS
We studied the progression of myasthenia gravis (MG) disease burden and medication adjustment among MG Patient Registry participants.
METHODS
Participants diagnosed with MG (age ≥18 years), registered between July 1, 2013 and July 31, 2018 and completing both 6- and 12-month follow-up surveys, were included in this investigation. Participants were grouped into high-burden (Myasthenia Gravis Activity of Daily Living scale [MG-ADL] score ≥6) and low-burden (MG-ADL <6) groups based on MG-ADL scores at enrollment. Demographics and disease history were compared between groups. MG-ADL score change and medication changes (escalation, no change, de-escalation) between enrollment and 12-month follow-up were compared between groups. Minimal symptom expression (MSE, MG-ADL <2) at 12 months was compared between groups. Logistic regression analysis was performed to study factors associated with MSE at 12 months.
RESULTS
In total, 520 participants (56% female) were included in high-burden (n = 248) and low-burden (n = 272) groups. Those in the high-burden group were more likely to be younger, female, and have shorter disease duration. At 12 months, MSE was achieved in 6% of the high-burden group and newly achieved (42 of 201, 21%) or maintained (52 of 71, 73%) in the low-burden group. In the multivariable analysis, being in the high-burden group and use of pyridostigmine were associated with less likelihood of MSE, whereas MG-ADL score improvement (>2 or >20%) at 6 months significantly increased the likelihood of achieving MSE at 12 months (P = .0004).
DISCUSSION
In both groups, but more so in the high-burden group, patients infrequently achieved MSE after 1 year of MG treatment. Baseline low disease burden, improvement at 6 months and no pyridostigmine use were associated with a higher likelihood of MSE at 12 months.
Topics: Activities of Daily Living; Adolescent; Cost of Illness; Female; Follow-Up Studies; Humans; Male; Myasthenia Gravis; Pyridostigmine Bromide; Registries
PubMed: 35673964
DOI: 10.1002/mus.27659 -
Frontiers in Pediatrics 2022Myasthenia gravis is an autoimmune disease mediated by B cells and is associated with acetylcholine receptor (AChR) and muscle-specific receptor tyrosine kinase (MuSK)...
Myasthenia gravis is an autoimmune disease mediated by B cells and is associated with acetylcholine receptor (AChR) and muscle-specific receptor tyrosine kinase (MuSK) antibodies in the postsynaptic membrane at the neuromuscular junction. The presence of both antibodies in the serum of patients with myasthenia gravis has been rarely reported. Case description: A 9-year-old girl was admitted to our hospital with the chief complaints of reduced facial expression for 3 months and unclear speech and choking from drinking water for 2 months. The diagnosis of generalized myasthenia gravis was made based on clinical manifestations, repetitive electrical nerve stimulation, neostigmine tests, specific antibody tests and other auxiliary examinations. We found the rare coexistence of two key antibodies (anti-AChR and anti-MuSK antibodies) in the patient's serum. The patient experienced myasthenic crisis and received respiratory support even though she was taking prednisone therapy. Due to the poor response to treatment with pyridostigmine bromide, glucocorticoids and IVIG, we administered rituximab therapy, and she responded well and achieved clinical remission. This suggests that clinicians should pay more attention to atypical cases and antibody detection. Rituximab should be considered when conventional treatment fails.
PubMed: 35633954
DOI: 10.3389/fped.2022.788353