Myasthenic crisis.
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ABSTRACT:
SUBMITTER: Wendell LC
PROVIDER: S-EPMC3726100 | biostudies-other | 2011 Jan
REPOSITORIES: biostudies-other
Publications
Myasthenic crisis is a complication of myasthenia gravis characterized by worsening of muscle weakness, resulting in respiratory failure that requires intubation and mechanical ventilation. Advances in critical care have improved the mortality rate associated with myasthenic crisis. This article reviews the epidemiology of myasthenic crisis and discusses patient evaluation. Therapeutic options including mechanical ventilation and pharmacological and surgical treatments are also discussed. ...[more]
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Project description:Objective Myasthenic crisis (MC) is considered the most severe adverse event in patients with myasthenia gravis. The present retrospective study was performed to evaluate the predictors of clinical outcomes in patients with MC. Methods The medical charts of 33 patients (19 women, 14 men) with 76 MC attacks from 2002 to 2014 were retrospectively reviewed. Early extubation (?7 days) and prolonged ventilation (>15 days) during the MC were used to assess patient outcomes. Results Among the 33 patients, 24 (72.7%) had positive acetylcholine receptor antibody test results and 20 (60.6%) experienced recurrent MC attacks (?2 episodes) during follow-up (median 83.6 months, range 1.5-177 months). Plasma exchange during an MC was significantly associated with early extubation. Male sex, older age (>50 years), atelectasis, and ventilator-associated pneumonia significantly contributed to prolonged ventilation. In 22 patients who underwent thymectomy, both the duration between MC attacks and the mean number of MC attacks were significantly reduced after surgery. Conclusions Plasma exchange during MC attacks was found to be important for early extubation; older patients and those with atelectasis or ventilator-associated pneumonia were more vulnerable to prolonged ventilation. Thymectomy may be useful to prevent recurrence of MC.
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| S-EPMC7415338 | biostudies-literature
Project description:Mechanical ventilation in myasthenic crisis is not standardized and is at high risk of failure. We investigated liberation from mechanical ventilation during myasthenic crisis using a prolonged spontaneous breathing trials (SBT) and sequential pulmonary function tests (PFT). In this retrospective monocenter study, we included patients admitted for a first episode of myasthenic crisis between January 2001 and January 2018. The primary outcome was the incidence of weaning failure upon first extubation in our cohort of patients with MC. Secondary objectives were to determine risk factors and outcome associated with weaning failure upon first extubation in MC. We also compared the characteristics of patients with prolonged weaning. 126 episodes of MC were analyzed. Patient's age was 64 [42-76] years with 72/126 (56.5%) being women. The median delay between weaning initiation and first extubation was 6 [3-10] days and the median total length of MV was 14 [10-23] days. 118/126 (93.7%) patients underwent prolonged SBT of 8 h or more prior to first extubation. The overall weaning failure rate was 18/126 (14.3%). Extubation was more often successful when the factor precipitating the myasthenic crisis was identified (86/108 (79.6%) vs. 8/18 (44.4%); p = 0.004), whereas PFT was similar in failure or successes. Most weaning failures upon first extubation attempt (11/18; 61%) were attributed to an insufficient stabilization of myasthenia gravis. Duration of mechanical ventilation, an infectious trigger and maximal inspiratory pressure upon intubation were independent risk factors for prolonged weaning. In myasthenic crisis, a standardized protocol including prolonged SBT and respiratory function tests might improve the success of first extubation without prolonging mechanical ventilation. The results of this single center study warrant further evaluation in interventional trials.
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Project description:ObjectiveMyasthenia gravis (MG) is an autoimmune disease caused by autoantibodies against neuromuscular junctions. Myasthenic crisis (MC) represents the most severe state of MG with high in-hospital mortality. We aimed to identify immune signatures using in-depth profiling in MC, and to assess the correlations between immune biomarkers with clinical severity longitudinally.MethodsWe studied 181 participants including 57 healthy controls, 96 patients with MG who never experienced crisis and 28 MC patients from December 2018 through June 2020. Follow-up visits occurred prospectively from crisis to 6 months off-mechanical ventilation. The frequencies of 20 CD4+ T subpopulations and 18 serum cytokines were associated with clinical scores using correlations and principal component analysis.ResultsPatients in crisis exhibited a proinflammatory CD4+ T response with elevated Th1 (P = 0.026), and Th17 cells (P = 0.032); decreased T follicular helper 2 (Tfh2) cells (P < 0.001), Tnaive in Tfh cells (P < 0.001), ICOS- Tfh cells (P = 0.017), and T central memory in Tfh (P = 0.022) compared with controls, and increased frequencies of Tregs (P = 0.026) and Tfh17 (P = 0.045) compared with non-crisis MG. Cytokine cascade was identified in crisis including the ones associated with Th1 (IL-1β/2/12p70/18/27/IFN-γ/TNF-α), Th2 (IL-4/5/13), Th17 (IL-6/17A/21/22/23/GM-CSF), Th9 (IL-9), and Treg (IL-10). Longitudinally, seven immune biomarkers including Tregs, IL-2/4/17A/IFN-γ/TNF-α/GM-CSF had significant correlations with MG-activities of daily living score.InterpretationVigorous inflammatory CD4+ T signatures were identified in MC and are associated with clinical severity. Future research is needed to explore its potential candidacy for therapeutic intervention and predicting impending crisis.
| S-EPMC8045923 | biostudies-literature
Project description:BackgroundMyasthenia gravis (MG) is the most prevalent autoimmune disorder affecting the neuromuscular junction. A rapid deterioration in respiratory muscle can lead to a myasthenic crisis (MC), which represents a life-threatening condition with high mortality in MG. Multiple CD4+ T subsets and hypercytokinemia have been identified in the peripheral pro-inflammatory milieu during the crisis. However, the pathogenesis is complicated due to the many types of cells involved, leaving the underlying mechanism largely unexplored.MethodsWe conducted single-cell transcriptomic and immune repertoire sequencing on 33,577 peripheral blood mononuclear cells (PBMCs) from two acetylcholine receptor antibody-positive (AChR +) MG patients during MC and again three months post-MC. We followed the Scanpy workflow for quality control, dimension reduction, and clustering of the single-cell data. Subsequently, we annotated high-resolution cell types utilizing transfer-learning models derived from publicly available single-cell immune datasets. RNA velocity calculations from unspliced and spliced mRNAs were applied to infer cellular state progression. We analyzed cell communication and MG-relevant cytokines and chemokines to identify potential inflammation initiators.ResultsWe identified a unique subset of monocytes, termed monocytes 3 (FCGR3B+ monocytes), which exhibited significant differential expression of pro-inflammatory signaling pathways during and after the crisis. In line with the activated innate immune state indicated by MC, a high neutrophil-lymphocyte ratio (NLR) was confirmed in an additional 22 AChR + MC patients in subsequent hemogram analysis and was associated with MG-relevant clinical scores. Furthermore, oligoclonal expansions were identified in age-associated B cells exhibiting high autoimmune activity, and in CD4+ and CD8+ T cells demonstrating persistent T exhaustion.ConclusionsIn summary, our integrated analysis of single-cell transcriptomics and TCR/BCR sequencing has underscored the role of innate immune activation which is associated with hypercytokinemia in MC. The identification of a specific monocyte cluster that dominates the peripheral immune profile may provide some hints into the etiology and pathology of MC. However, future functional studies are required to explore causality.
| S-EPMC10464341 | biostudies-literature
Project description:Immune checkpoint inhibitors (ICIs) have emerged in recent years as promising treatment options for several malignant tumors. However, ICI therapy has also been associated with various immune-related adverse events (irAEs), especially for patients with preexisting autoimmune status, which sometimes can be life-threatening. A 68-year-old woman diagnosed with metastatic thymoma was treated with camrelizumab, a new ICI, as her antitumor protocol. Eleven days after the first dose of camrelizumab, the patient was admitted to our hospital with symptoms of dyspnea, fatigue, and poor appetite. Workups on admission indicated dramatically elevated transaminase, troponin I, creatine kinase, and a new-onset conduction abnormality on electrocardiography. After detailed evaluation, ICI-related myocarditis, myositis, and hepatitis were diagnosed, and therapies including intravenous methylprednisolone were administered. Coronary angiography was performed to exclude acute coronary syndrome due to dynamic electrocardiography changes on day 3. She lapsed into a coma with respiratory muscle failure on the next day, which was highly suspected of myasthenic crisis. Mechanical ventilation and higher dose of methylprednisolone plus intravenous immunoglobulin were applied immediately. However, the third atrioventricular block occurred within the same day, and an urgent temporary pacemaker was placed. More seriously, refractory ventricular tachycardia (VT) occurred subsequently, and even multiple antiarrhythmic drugs used in combination failed to alleviate the VT storm. On day 5 of hospitalization, she suffered from ventricular fibrillation and died of cardiac arrest. In clinical practice, close follow-up should be conducted after ICI treatment, especially for patients already with or at high risk for autoimmune disorders. A multidisciplinary team approach is of importance for better management of patients with multiple organ involvement.
| S-EPMC9411010 | biostudies-literature
Project description:Myasthenia gravis (MG) is a neurological autoimmune disorder characterized by muscle weakness and fatigue. It is a B cell-mediated disease caused by pathogenic antibodies directed against various components of the neuromuscular junction (NMJ). Despite the wide range of adverse effects, current treatment is still based on non-specific immunosuppression, particularly on long-term steroid usage. The increasing knowledge regarding the pathogenic mechanisms of MG has however allowed to create more target-specific therapies. A very attractive therapeutic approach is currently offered by monoclonal antibodies (mAbs), given their ability to specifically and effectively target different immunopathological pathways, such as the complement cascade, B cell-related cluster of differentiation (CD) proteins, and the human neonatal Fc receptor (FcRn). Up to now, eculizumab, a C5-directed mAb, has been approved for the treatment of generalized MG (gMG) and efgartigimod, a FcRn inhibitor, has just been approved by the U.S. Food and Drug Administration for the treatment of anti-acetylcholine receptor (AChR) antibody positive gMG. Other mAbs are currently under investigation with encouraging preliminary results, further enriching the new range of therapeutic possibilities for MG. This review article provides an overview of the present status of mAb-based therapies for MG, which offer an exciting promise for better outcomes by setting the basis of a precision medicine approach.
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Project description:Background:Myasthenic crisis can induce Takotsubo cardiomyopathy leading to transient systolic and diastolic left ventricular dysfunction and wall-motion abnormalities, including the characteristic apical ballooning. We aimed to define the clinical features of this disease entity. Methods:A systematic review was conducted to examine the characteristics of Takotsubo cardiomyopathy presenting in myasthenia gravis patients. Case reports were accessed by searching MEDLINE/PubMed, Google Scholar, CINAHL, and Web of Science databases. 523 articles were identified and 14 were selected for review. Results:Takotsubo cardiomyopathy presenting in myasthenia gravis' patients tends to affect women between the ages of 40 to 77. History of atrial fibrillation or hypertension was found in a minority of cases. Generalized weakness, fatigue, dysphagia and respiratory distress were common at presentation. Vital signs demonstrated normal blood pressure without tachycardia or bradycardia. Elevated values of troponins, creatine kinase (CK), and CK-MB isoenzymes were recorded. ST-segment elevation followed by T-wave inversion were predominantly found on electrocardiograms. Apical abnormalities in the form of ballooning, hypokinesia, or sparing and reduced left ventricular ejection fraction (?45%) were observed using transthoracic echocardiogram or left ventriculography. Coronary angiography demonstrated no obstructive lesions. Ventilatory support, cholinesterase inhibitors and glucocorticoids resulted in the recovery or improvement of the left ventricular ejection fraction and hemodynamic stability. Only a minority of patients died of refractory heart failure. Treatment with inotropes and/or vasopressors led to poorer outcomes, including death or intractable heart failure. Conclusion:The management of Takotsubo cardiomyopathy developing in myasthenia gravis patients should focus on addressing the myasthenic crisis, while proving supportive care in and intensive care setting.
| S-EPMC6728802 | biostudies-literature
Project description:BackgroundMyasthenic crisis (MC) and disease exacerbation in myasthenia gravis (MG) are associated with significant lethality and continue to impose a high disease burden on affected patients. Therefore, we sought to determine potential predictors for MC and exacerbation as well as to identify factors affecting outcome.MethodsWe examined a retrospective, observational cohort study of patients diagnosed with MG between 2000 and 2021 with a mean follow-up of 62.6 months after diagnosis from eight tertiary hospitals in Germany. A multivariate Cox regression model with follow-up duration as the time variable was used to determine independent risk factors for MC and disease exacerbation.Results815 patients diagnosed with MG according to national guidelines were included. Disease severity at diagnosis (quantitative MG score or Myasthenia Gravis Foundation of America class), the presence of thymoma and anti-muscle specific tyrosine kinase-antibodies were independent predictors of MC or disease exacerbation. Patients with minimal manifestation status 12 months after diagnosis had a lower risk of MC and disease exacerbation than those without. The timespan between diagnosis and the start of immunosuppressive therapy did not affect risk. Patients with a worse outcome of MC were older, had higher MGFA class before MC and at admission, and had lower vital capacity before and at admission. The number of comorbidities, requirement for intubation, prolonged mechanical ventilation, and MC triggered by infection were associated with worse outcome. No differences between outcomes were observed comparing treatments with IVIG (intravenous immunoglobulin) vs. plasma exchange vs. IVIG together with plasma exchange.ConclusionsMC and disease exacerbations inflict a substantial burden of disease on MG patients. Disease severity at diagnosis and antibody status predicted the occurrence of MC and disease exacerbation. Intensified monitoring with emphasis on the prevention of infectious complications could be of value to prevent uncontrolled disease in MG patients.
| S-EPMC9005160 | biostudies-literature
Project description:BackgroundMyasthenic crisis (MC) often requires admission to an intensive care unit (ICU).MethodsWe retrospectively investigated 113 consecutive patients with first MC admitted to the neurological ICU. Patients' demographic, clinical and other characteristics were examined, as well as therapeutic interventions, mortality and functional outcome.ResultsMC patients at first onset admitted to neurological ICU had a mortality rate of 18.6%. PCO2 level before intubation and score on Myasthenia Gravis-Activities of Daily Living (MG-ADL) scale at MC onset correlated with duration of ventilation and length of ICU stay. Compared with patients with good functional outcome, patients with intermediate or poor functional outcome were older at first MC onset, had lower pH and PO2, and had higher PCO2 before intubation. Multivariate logistic analysis identified pre-intubation PCO2 level as an independent predictor of survival. Cox regression showed that age at first MC onset requiring ICU management was the factor which significantly influenced the mortality.ConclusionsOur results suggest that PCO2 before intubation and MG-ADL score at MC onset may be useful indicators of more severe disease likely to require extensive respiratory support and ICU management. Higher pre-intubation PCO2 indicates chronic respiratory acidosis that can increase risk of severe disability and death, especially in patients with older age at first MC onset.
| S-EPMC6642475 | biostudies-literature