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Molecular Medicine (Cambridge, Mass.) Nov 2022Respiratory failure in severe coronavirus disease 2019 (COVID-19) is associated with a severe inflammatory response. Acetylcholine (ACh) reduces systemic inflammation in... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Respiratory failure in severe coronavirus disease 2019 (COVID-19) is associated with a severe inflammatory response. Acetylcholine (ACh) reduces systemic inflammation in experimental bacterial and viral infections. Pyridostigmine increases the half-life of endogenous ACh, potentially reducing systemic inflammation. We aimed to determine if pyridostigmine decreases a composite outcome of invasive mechanical ventilation (IMV) and death in adult patients with severe COVID-19.
METHODS
We performed a double-blinded, placebo-controlled, phase 2/3 randomized controlled trial of oral pyridostigmine (60 mg/day) or placebo as add-on therapy in adult patients admitted due to confirmed severe COVID-19 not requiring IMV at enrollment. The primary outcome was a composite of IMV or death by day 28. Secondary outcomes included reduction of inflammatory markers and circulating cytokines, and 90-day mortality. Adverse events (AEs) related to study treatment were documented and described.
RESULTS
We recruited 188 participants (94 per group); 112 (59.6%) were men; the median (IQR) age was 52 (44-64) years. The study was terminated early due to a significant reduction in the primary outcome in the treatment arm and increased difficulty with recruitment. The primary outcome occurred in 22 (23.4%) participants in the placebo group vs. 11 (11.7%) in the pyridostigmine group (hazard ratio, 0.47, 95% confidence interval 0.24-0.9; P = 0.03). This effect was driven by a reduction in mortality (19 vs. 8 deaths, respectively).
CONCLUSION
Our data indicate that adding pyridostigmine to standard care reduces mortality among patients hospitalized for severe COVID-19.
Topics: Adult; Male; Humans; Middle Aged; Female; Pyridostigmine Bromide; SARS-CoV-2; Respiration, Artificial; Inflammation; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 36348276
DOI: 10.1186/s10020-022-00553-x -
Brain and Behavior Dec 2022This review highlights the potential mechanisms of neuromuscular manifestation of COVID-19, especially myasthenia gravis (MG). (Review)
Review
INTRODUCTION
This review highlights the potential mechanisms of neuromuscular manifestation of COVID-19, especially myasthenia gravis (MG).
METHODS
An extensive literature search was conducted by two independent investigators using PubMed/MEDLINE and Google Scholar from its inception to December 2020.
RESULTS
Exacerbations of clinical symptoms in patients of MG who were treated with some commonly used COVID-19 drugs has been reported, with updated recommendations of management of symptoms of neuromuscular disorders. Severe acute respiratory syndrome coronavirus 2 can induce the immune response to trigger autoimmune neurological disorders.
CONCLUSIONS
Further clinical studies are warranted to indicate and rather confirm if MG in the setting of COVID-19 can pre-existent subclinically or develop as a new-onset disease.
Topics: Humans; SARS-CoV-2; COVID-19; Myasthenia Gravis
PubMed: 36306401
DOI: 10.1002/brb3.2789 -
Acta Neuropathologica Communications Oct 2022Chemical and pharmaceutical exposures have been associated with the development of Gulf War Illness (GWI), but how these factors interact with the pathophysiology of...
Chemical and pharmaceutical exposures have been associated with the development of Gulf War Illness (GWI), but how these factors interact with the pathophysiology of traumatic brain injury (TBI) remains an area of study that has received little attention thus far. We studied the effects of pyridostigmine bromide (an anti-nerve agent) and permethrin (a pesticide) exposure in a mouse model of repetitive mild TBI (r-mTBI), with 5 impacts over a 9-day period, followed by Gulf War (GW) toxicant exposure for 10 days beginning 30 days after the last head injury. We then assessed the chronic behavioral and pathological sequelae 5 months after GW agent exposure. We observed that r-mTBI and GWI cumulatively affect the spatial memory of mice in the Barnes maze and result in a shift of search strategies employed by r-mTBI/GW exposed mice. GW exposure also produced anxiety-like behavior in sham animals, but r-mTBI produced disinhibition in both the vehicle and GW treated mice. Pathologically, GW exposure worsened r-mTBI dependent axonal degeneration and neuroinflammation, increased oligodendrocyte cell counts, and increased r-mTBI dependent phosphorylated tau, which was found to colocalize with oligodendrocytes in the corpus callosum. These results suggest that GW exposures may worsen TBI-related deficits. Veterans with a history of both GW chemical exposures as well as TBI may be at higher risk for worse symptoms and outcomes. Subsequent exposure to various toxic substances can influence the chronic nature of mTBI and should be considered as an etiological factor influencing mTBI recovery.
Topics: Mice; Animals; Gulf War; Brain Concussion; Pyridostigmine Bromide; Permethrin; Disease Models, Animal; Brain Injuries, Traumatic; Pesticides; Pharmaceutical Preparations
PubMed: 36258255
DOI: 10.1186/s40478-022-01449-x -
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 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 -
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