Dynamic changes of peripheral inflammatory markers link with disease severity and predict short-term poor outcome of myasthenia gravis.

The relationship between peripheral inflammatory markers, their dynamic changes, and the disease severity of myasthenia gravis (MG) is still not fully understood. Besides, the possibility of using it to predict the short-term poor outcome of MG patients have not been demonstrated. This study aims to investigate the relationship between peripheral inflammatory markers and their dynamic changes with Myasthenia Gravis Foundation of America (MGFA) classification (primary outcome) and predict the short-term poor outcome (secondary outcome) in MG patients. The study retrospectively enrolled 154 MG patients from June 2016 to December 2021. The logistic regression was used to investigate the relationship of inflammatory markers with MGFA classification and determine the factors for model construction presented in a nomogram. Finally, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were utilized to evaluate the incremental capacity. Logistic regression revealed significant associations between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), aggregate index of systemic inflammation (AISI) and MGFA classification (p = 0.013, p = 0.032, p = 0.017, respectively). Incorporating dynamic changes of inflammatory markers into multivariable models improved their discriminatory capacity of disease severity, with significant improvements observed for NLR, systemic immune-inflammation index (SII) and AISI in NRI and IDI. Additionally, AISI was statistically associated with short-term poor outcome and a prediction model incorporating dynamic changes of inflammatory markers was constructed with the area under curve (AUC) of 0.953, presented in a nomograph. The inflammatory markers demonstrate significant associations with disease severity and AISI could be regarded as a possible and easily available predictive biomarker for short-term poor outcome in MG patients.

Serum amyloid A facilitates expansion of CD4+ T cell and CD19+ B cell subsets implicated in the severity of myasthenia gravis patients.

Serum amyloid A (SAA) is a clinically useful inflammatory marker involved in the pathogenesis of autoimmune diseases. This study aimed to explore the SAA levels in a cohort of patients with myasthenia gravis (MG) in relation to disease-related clinical parameters and myasthenic crisis (MC) and elucidate the effects of SAA on immune response. A total of 82 MG patients including 50 new-onset MG patients and 32 MC patients were enrolled in this study. Baseline data and laboratory parameters of all enrolled MG patients were routinely recorded through electronic medical systems. SAA levels were measured by enzyme-linked immunosorbent assay (ELISA) kit. CD4+ T and CD19+ B cell subsets were analyzed by flow cytometry. In vitro, human recombinant SAA (Apo-SAA) was applied to stimulate peripheral blood mononuclear cells (PBMCs) from MG patients to observe the effect on T and B cell differentiation. Our results indicated that SAA levels in new-onset MG patients were higher than those in controls and were positively correlated with QMG score, MGFA classification, plasmablast cells, IL-6, and IL-17 levels. Subgroup analysis revealed that SAA levels were increased in generalized MG (GMG) patients than in ocular MG (OMG), as well as elevated in late-onset MG (LOMG) than in early-onset MG (EOMG) and higher in MGFA III/IV compared with MGFA I/II. The ROC curve demonstrated that SAA showed good diagnostic value for MC, especially when combined with NLR. In vitro, Apo-SAA promoted the Th1 cells, Th17 cells, plasmablast cells, and plasma cells differentiation in MG PBMCs. The present findings suggested that SAA was increased in MG patients and promoted expansion of CD4+ T cell and CD19+ B cell subsets, which implicated in the severity of MG patients.

Clinical outcome and peripheral immune profile of myasthenic crisis with omicron infections: A prospective cohort study.

The impact of Omicron infections on the clinical outcome and immune responses of myasthenia gravis (MG) remained largely unknown. From a prospective multicenter MG cohort (n = 189) with 197 myasthenic crisis (MC), we finally included 41 independent MG patients to classify into two groups: the Omicron Group (n = 13) and the Control Group (n = 28). In this matched cohort study, all-cause mortality was 7.69% (1/13) in Omicron Group and 14.29% (4/28) in Control Group. A higher proportion of elevated serum IL-6 was identified in the Omicron Group (88.89% vs 52.38%, P = 0.049). In addition, the proportions of CD3+CD8+T in lymphocytes and Tregs in CD3+CD4+ T cells were significantly elevated in the Omicron Group (both P = 0.0101). After treatment, the Omicron Group exhibited a marked improvement in MG-ADL score (P = 0.026) and MG-QoL-15 (P = 0.0357). MCs with Omicron infections were associated with elevated serum IL-6 and CD3+CD8+T response. These patients tended to present a better therapeutic response after fast-acting therapies and anti-IL-6 treatment.

Burden of illness and costs in patients with myasthenia gravis currently receiving treatment in the United States.

INTRODUCTION/AIMS: If myasthenia gravis (MG) symptoms are inadequately controlled, patients may experience exacerbations or life-threatening myasthenic crises. Patients with inadequately controlled MG symptoms tend to be treated with chronic intravenous immunoglobulin (IVIg) therapy and/or multiple immunosuppressant therapies (ISTs). This study aimed to examine disease burden, healthcare resource utilization, and associated costs in these patients. METHODS: This was a retrospective observational study using a claims database. Patients with MG were classified into three cohorts based on treatment over a 1-y follow-up period: (a) treated with four or more IVIg episodes (chronic IVIg cohort); (b) received two or more non-steroidal ISTs (NSISTs) sequentially (multiple NSIST cohort); (c) received neither chronic IVIg nor multiple NSISTs (reference cohort). Incidences of crises and exacerbations and annual healthcare costs in each cohort were estimated. RESULTS: In total, 3516 patients with MG were included in the analysis. Compared with the reference cohort (n = 2992), the MG crisis rate was approximately twice as high in both the chronic IVIg (n = 324) and multiple NSIST (n = 291) cohorts (p < 0.001); and the MG exacerbation rate was approximately four-fold higher in the chronic IVIg cohort (p < 0.001) and three-fold higher in the multiple NSIST cohort (p < 0.001). Median annual MG-related inflation-adjusted total healthcare costs were higher in the chronic IVIg ($81,900) and multiple NSIST ($30,300) cohorts than in the reference cohort ($2540). DISCUSSION: The burden of crises/exacerbations was substantially higher and healthcare costs were considerably greater in patients with MG treated with chronic IVIg or multiple NSISTs than in patients not receiving these treatments.

Peripheral immune landscape for hypercytokinemia in myasthenic crisis utilizing single-cell transcriptomics.

BACKGROUND: Myasthenia 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. METHODS: We 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. RESULTS: We 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. CONCLUSIONS: In 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.

Myasthenic crisis.

Myasthenic crisis (MC) is a life-threatening manifestation of myasthenia gravis (MG) defined by respiratory insufficiency that requires the use of invasive or non-invasive ventilation. This is often the result of respiratory muscle weakness but can also be due to bulbar weakness with upper airway collapse. MC occurs in approximately 15%-20% of patients with MG usually within the first 2 to 3 y of the disease course. Many crises have a specific trigger with respiratory infections being most common; however, no specific trigger is found in 30%-40% of patients. MG patients with a history of MC, severe disease, oropharyngeal weakness, muscle-specific kinase (MuSK) antibodies and thymoma appear to be at higher risk. Most episodes of MC do not occur suddenly, providing a window of opportunity for prevention. Immediate treatment is directed toward airway management and removing any identified triggers. Plasmapheresis is preferred over intravenous immune globulin as the treatments of choice for MC. The majority of patients are able to be weaned from mechanical ventilation within 1 mo and the outcomes of MC are generally favorable. The mortality rate in United States cohorts is less than 5% and mortality in MC seems to be driven by age and other medical co-morbidities. MC does not appear to affect long-term prognosis as many patients are able to eventually achieve good MG control.

Treatment patterns in myasthenia gravis: A United States health claims analysis.

INTRODUCTION/AIMS: Limited knowledge exists on treatment patterns in clinical practice in patients with myasthenia gravis (MG). In this study we examined MG treatment patterns in the United States. METHODS: Adult patients newly diagnosed with MG were identified from the IBM MarketScan insurance claims database. Patients with ≥2 MG International Classification of Disease diagnosis codes ≥3 months apart were retrospectively followed from the date of their first MG diagnosis record or start of treatment with acetylcholinesterase inhibitors (AChEI), intravenous (IV) or subcutaneous (SC) immunoglobulin (Ig), or plasma exchange (PLEx) therapy. Based on treatment received at any time during the follow-up period, patients were segmented into six main treatment cohorts. Exacerbations and use of IVIg, SCIg, or PLEx after the index date were identified. RESULTS: During 2010 to 2019, 7,194 patients were followed for up to 10 (median, 2.3) years. Of 6,539 treated patients, 6,462 (99%) were ever treated with AChEI and/or corticosteroids (CS); 95% were first treated with AChEI and/or CS only; 33% received ≥1 nonsteroid immunosuppressive treatment (IST) and 2% received a biologic. During treatment with first IST (n = 2,166), patients experienced 42% and 94% higher incidence rates of exacerbations and IVIg, respectively, compared with AChEI and/or CS (n = 6,242), and 33% and 23% higher, respectively, compared with a second IST (n = 353). DISCUSSION: Many patients experienced exacerbations and received rescue therapy despite treatment, suggesting current treatments may not provide adequate disease control for some patients and that additional treatment options should be explored.

Myasthenia gravis and independent risk factors for recurrent infection: a retrospective cohort study.

BACKGROUND: Approximately 10% to 20% of myasthenia gravis (MG) patients have experienced a myasthenic crisis (MC), which contributes to morbidity and mortality. MC triggered by infection is associated with poor outcomes. However, there is a lack of prognostic factors that clinicians can utilize to target interventions for preventing recurrent infection-triggered MC. This study aimed to characterize clinical manifestations, comorbidities, and biochemical profiles associated with recurrent infection-triggered MC in MG patients. METHODS: This retrospective study included 272 MG patients hospitalized with an infection requiring at least 3 days of antibiotics from January 2001 to December 2019. Patients were further stratified into non-recurrent or recurrent infection groups. Clinical features such as gender, age, concomitant diseases, acetylcholine receptor antibodies and biochemical data (including electrolytes and coagulants), muscle strength of pelvic and shoulder girdle, bulbar and respiratory function, management with an endotracheal tube, Foley catheter, or plasmapheresis, duration of hospitalization, and culture pathogens were recorded. RESULTS: The recurrent infection group was significantly older than the non-recurrent group (median age, 58.5 versus 52.0 years). Pneumonia was the most common infection and Klebsiella pneumoniae was the most common pathogen. The presence of concomitant diabetes mellitus, activated partial thromboplastin time prolongation, the duration of hospitalization, and hypomagnesaemia were independently associated with recurrent infection. The presence of deep vein thrombosis, thymic cancer, and electrolyte imbalances i.e., hypokalemia, and hypoalbuminemia were significantly associated with a risk for infection. The influence of endotracheal intubation, anemia, and plasmapheresis during hospitalization were inconsistent. CONCLUSIONS: The independent risk factors for recurrent infections in MG patients identified in this study include the presence of concomitant diabetes mellitus, hypomagnesaemia, activated partial thromboplastin time prolongation, and longer duration of hospitalization, highlighting the need for targeted interventions to prevent recurrent infections in this population. Further research and prospective studies are warranted to validate these findings and refine interventions for optimizing patient care.

Analysis of length of stay and treatment emergent complications in hospitalized myasthenia gravis patients with exacerbation.

INTRODUCTION: AIMS Myasthenia Gravis (MG) is an autoimmune neuromuscular disease in which patients suffer from recurrent exacerbation. There are insufficient data measuring the effects of the resources employed before and during acute exacerbation on subsequent disease outcomes. This study aims to identify factors which lead to lengthened hospital stay. METHODS: This is a retrospective chart review of acute MG exacerbations requiring hospitalization. Exacerbations were identified using ICD-9/ICD-10 codes and considered the following variables: age and Myasthenia Gravis Foundation of America (MGFA) class at initial MG diagnosis, age and MGFA class at exacerbation, sex, thymectomy, cause of exacerbation, treatment regimen at time of exacerbation, inpatient treatment regimen, length of hospital stay (LOS), intubation, use of noninvasive ventilation, complications, and disposition. RESULTS: Seventy patients with 141 hospitalizations were identified. Crisis management characterized by intubation and plasmapheresis positively correlated with LOS (both p < .001). Almost 1/5 hospitalizations required intubation. Previous thymectomy negatively correlated with LOS (p < .05). In contrast, male sex correlated with longer LOS (p < .05). One-third of hospital stays were followed by discharge to a post-acute care facility, 7% home with home health, and 1 hospitalization resulted in death. DISCUSSION: Plasmapheresis, intubation, and male sex were associated with increased LOS in acute MG exacerbation. Intubation appears to be the strongest predictor of LOS. Those with previous thymectomy had shorter hospital stays. The role of thymectomy in the acute setting merits further analysis.

Starting eculizumab as rescue therapy in refractory myasthenic crisis.

INTRODUCTION: Myasthenia gravis is a long-lasting autoimmune neuromuscular disease caused by antibodies attacking the neuromuscular junction, which can result in muscle weakness, fatigue, and respiratory failure in severe cases. Myasthenic crisis is a life-threatening event that requires hospitalization and treatments with intravenous immunoglobulin or plasma exchange. We reported the case of an AChR-Ab-positive myasthenia gravis patient with refractory myasthenic crisis, in which starting eculizumab as rescue therapy led to a complete resolution of the acute neuromuscular condition. CASE PRESENTATION: A 74-year-old man diagnosed with myasthenia gravis. ACh-receptor antibodies positivity comes to our observation for a recrudescence of symptoms, unresponsive to conventional rescue therapies. Due to the clinical worsening over the following weeks, the patient was admitted to intensive care unit, where he underwent therapy with eculizumab. About 5 days after the treatment, there was a significant and complete recovery of clinical condition with weaning-off from invasive ventilation and discharge to outpatient regimen, with reduction of steroid intake and biweekly maintenance with eculizumab. DISCUSSION: Eculizumab, a humanized monoclonal antibody that inhibits complement activation, is now approved as treatment for refractory generalized myasthenia gravis with anti-AChR antibodies. The use of eculizumab in myasthenic crisis is still investigational, but this case report suggests that it may be a promising treatment option for patients with severe clinical condition. Ongoing clinical trials will be needed to further evaluate the safety and efficacy of eculizumab in myasthenic crisis.

Plasma exchange versus intravenous immunoglobulin in AChR subtype myasthenic crisis: A prospective cohort study.

Myasthenic crisis (MC) is a life-threatening state with respiratory failure in patients with myasthenia gravis (MG). The fast-acting immunomodulatory therapies for treating MC included plasma exchange (PE) and intravenous immunoglobulin (IVIG). However, the efficacy and the impact on antibody changes remained unknown. We prospectively followed 40 anti-acetylcholine receptors (AChR) antibody-positive MC patients who received either PE (n = 12) or IVIG (n = 28) at crisis. PE was associated with a reduced ICU stay length (p = 0.018) and an early response by the average changes in MGFA-QMG (p = 0.003), MMT (p = 0.020), and ADL (p = 0.011) at one-week off-ventilation. However, the clinical efficacy was equally comparable in both groups after 1 month. Post-treatment hemoglobin drop was significant in both groups, while IVIG was associated with a significant reduction in anti-AChR antibody titers (p < 0.001). This analysis provides real-world evidence in supporting the use of PE as a fast-acting therapy for shortening the ICU stay in AChR-associated MC.

Independent risk factors for myasthenic crisis and disease exacerbation in a retrospective cohort of myasthenia gravis patients.

BACKGROUND: Myasthenic 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. METHODS: We 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. RESULTS: 815 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. CONCLUSIONS: MC 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.

Poor responses and adverse outcomes of myasthenia gravis after thymectomy: Predicting factors and immunological implications.

Myasthenia gravis (MG) has been recognized as a series of heterogeneous but treatable autoimmune conditions. As one of the indispensable therapies, thymectomy can achieve favorable prognosis especially in early-onset generalized MG patients with seropositive acetylcholine receptor antibody. However, poor outcomes, including worsening or relapse of MG, postoperative myasthenic crisis and even post-thymectomy MG, are also observed in certain scenarios. The responses to thymectomy may be associated with the general characteristics of patients, disease conditions of MG, autoantibody profiles, native or ectopic thymic pathologies, surgical-related factors, pharmacotherapy and other adjuvant modalities, and the presence of comorbidities and complications. However, in addition to these variations among individuals, pathological remnants and the abnormal immunological milieu and responses potentially represent major mechanisms that underlie the detrimental neurological outcomes after thymectomy. We underscore these plausible risk factors and discuss the immunological implications therein, which may be conducive to better managing the indications for thymectomy, to avoiding modifiable risk factors of poor responses and adverse outcomes, and to developing post-thymectomy preventive and therapeutic strategies for MG.

A retrospective longitudinal cohort study of the clinical burden in myasthenia gravis.

BACKGROUND: Patients with generalized myasthenia gravis (MG) often experience debilitating exacerbations, with the possibility of life-threatening respiratory crises requiring hospitalization. Long-term longitudinal studies are needed to understand the burden of MG, including in patients whose disease is refractory to conventional treatment. METHODS: A retrospective, longitudinal, cohort study was conducted of patients in England aged ≥ 18 years with treatment-refractory or non-refractory MG, using data recorded during 1997-2016 in the Clinical Practice Research Datalink and the Hospital Episode Statistics databases. A control cohort of patients without MG, matched to the patients in the treatment-refractory MG cohort, was also identified. Outcome measures included myasthenic crises, MG exacerbations, MG-related hospitalizations, comorbidities, and all-cause mortality. Descriptive statistics were calculated for the overall MG population. For continuous variables, between-cohort comparisons were made using t tests for normally distributed data and Mann-Whitney U tests for non-normally distributed data. For categorical data, the comparisons were made by chi-squared tests. Differences in clinical outcomes between cohorts were modeled using negative binomial regression. RESULTS: A total of 1149 patients with MG were included. Overall, 18.4% of patients experienced myasthenic crises, 24.6% experienced exacerbations, and 38.6% underwent MG-related hospitalizations. Most of these events occurred within 2-3 years of diagnosis. Patients with MG refractory to conventional treatment (n = 66) experienced more exacerbations and MG-related hospitalizations than patients with non-refractory disease (n = 1083). Patients with refractory MG experienced a higher frequency of renal disease and hypertension compared with patients with non-refractory MG, and with matched patients without MG. They were also more likely to have diabetes and congestive heart failure than the matched controls. Rates of all-cause mortality during the follow-up period did not differ between patients with refractory MG and non-refractory MG. CONCLUSIONS: These results show that conventional treatments for MG are not adequately managing patients' symptoms and that patients with refractory MG are more likely to experience certain comorbidities than those with non-refractory MG or matched controls without MG. Future research should focus on the impact of newer targeted therapies on long-term clinical outcomes and comorbid conditions.

Early Tracheostomy Is Associated With Shorter Ventilation Time and Duration of ICU Stay in Patients With Myasthenic Crisis-A Multicenter Analysis.

BACKGROUND: Myasthenic crisis (MC) requiring mechanical ventilation (MV) is a rare and serious complication of myasthenia gravis. Here we analyzed the frequency of performed tracheostomies, risk factors correlating with a tracheostomy, as well as the impact of an early tracheostomy on ventilation time and ICU length of stay (LOS) in MC. METHODS: Retrospective chart review on patients treated for MC in 12 German neurological departments between 2006 and 2015 to assess demographic/diagnostic data, rates and timing of tracheostomy and outcome. RESULTS: In 107 out of 215 MC (49.8%), a tracheostomy was performed. Patients without tracheostomy were more likely to have an early-onset myasthenia gravis (27 [25.2%] vs 12 [11.5%], p = 0.01). Patients receiving a tracheostomy, however, were more frequently suffering from multiple comorbidities (20 [18.7%] vs 9 [8.3%], p = 0.03) and also the ventilation time (34.4 days ± 27.7 versus 7.9 ± 7.8, p < 0.0001) and ICU-LOS (34.8 days ± 25.5 versus 12.1 ± 8.0, p < 0.0001) was significantly longer than in non-tracheostomized patients. Demographics and characteristics of the course of the disease up to the crisis were not significantly different between patients with an early (within 10 days) compared to a late tracheostomy. However, an early tracheostomy correlated with a shorter duration of MV at ICU (26.2 days ± 18.1 versus 42.0 ± 33.1, p = 0.006), and ICU-LOS (26.2 days ± 14.6 versus 42.3 ± 33.0, p = 0.003). CONCLUSION: Half of the ventilated patients with MC required a tracheostomy. Poorer health condition before the crisis and late-onset MG were associated with a tracheostomy. An early tracheostomy (≤ day 10), however, was associated with a shorter duration of MV and ICU-LOS by 2 weeks.

Myasthenia gravis exacerbation and myasthenic crisis associated with COVID-19: case series and literature review.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction that can be exacerbated by many viral infections, including COVID-19. The management of MG exacerbations is challenging in this scenario. We report 8 cases of MG exacerbation or myasthenic crisis associated with COVID-19 and discuss prognosis and treatment based on a literature review. RESULTS: Most patients were female (7/8), with an average age of 47.1 years. Treatment was immunoglobulin (IVIG) in 3 patients, plasma exchange (PLEX) in 2 patients, and adjustment of baseline drugs in 3. In-hospital mortality was 25% and 37.5% in 2-month follow-up. DISCUSSION: This is the largest case series of MG exacerbation or myasthenic crisis due to COVID-19 to this date. Mortality was considerably higher than in myasthenic crisis of other etiologies. Previous treatment for MG or acute exacerbation treatment did not seem to interfere with prognosis, although sample size was too small to draw definitive conclusions. Further studies are needed to understand the safety and effectiveness of interventions in this setting, particularly of PLEX, IVIG, rituximab, and tocilizumab.

Perioperative Management of Patients With Myasthenia Gravis Undergoing Robotic-Assisted Thymectomy-A Retrospective Analysis and Clinical Evaluation.

OBJECTIVE: Postoperative myasthenic crisis with respiratory failure is a potentially lethal complication, warranting careful perioperative planning and extended postoperative surveillance of patients. Data on the incidence of postoperative respiratory failure and optimal management of patients after robotic-assisted thymectomy are limited. The objective of this study was to evaluate the incidence of respiratory complications and the need for intensive care unit (ICU) capacities after robotic-assisted thymectomy in patients with myasthenia gravis. DESIGN: Retrospective cohort study. SETTING: Single University hospital in Vienna, Austria, from January 2014 to December 2019. PARTICIPANTS: The authors included adult patients who underwent robotic-assisted thymectomy due to myasthenia gravis. MAIN RESULTS: Of 72 patients, 4 patients (5.6%) developed postoperative respiratory failure, needing noninvasive ventilation/intubation. Respiratory failure occurred within the first hours after extubation when patients still were under surveillance in the recovery room or in the ICU. One patient (1.4%) suffered from worsened myasthenic symptoms several days after surgery, and was treated with plasmapheresis. Sixty-five patients (90.3%) were extubated in the operating room, 35 of these (48.6%) were transferred to the ICU, and 30 patients (41.7%) primarily were transferred to the recovery room. Fourteen patients (19.4%) were transferred to the surgical ward after extended observation in the recovery room. Furthermore, after implementation of a standardized perioperative algorithm in 2020, a reduction of ICU admissions was achieved. CONCLUSIONS: After careful patient selection, planning, and postoperative patient evaluation, robotic-assisted thymectomy can be performed safely without postoperative surveillance in an ICU.

Takotsubo cardiomyopathy in the setting of a myasthenic crisis.

BACKGROUND: Myasthenic crisis is characterized by severe weakness in bulbar and respiratory muscles leading to respiratory failure and can be a natural result of myasthenia gravis or precipitate due to infections, surgeries, and pregnancy. It has been shown that stressful emotional events can lead to stress, or takotsubo cardiomyopathy. Takotsubo cardiomyopathy is characterized by transient reversible left ventricular dysfunction in the absence of obstructive artery disease with hypo- or akinesis of the apex with hypercontractility of the base. METHODS: Case report and review of literature. RESULTS: We report a 77-year old man with myasthenia gravis that was admitted to the neurological intensive care unit due to a myasthenic crisis. During the course of his treatment with plasma exchange, he developed hypotension with a reduced cardiac ejection fraction found on transthoracic electrocardiography. Repeat echocardiography 2 and 8 days later showed a normal ejection fraction and resolved cardiac function. CONCLUSION: While takotsubo cardiomyopathy rarely presents concurrently with a myasthenic crisis, its consideration is warranted in the face of cardiovascular decompensation. Given that several cardiac complications are known to be associated with myasthenic crisis, cardiac monitoring is advised. Nine reports describe takotsubo cardiomyopathy occurring concurrently with a myasthenic crisis; however, only one report demonstrates this association in the absence of concomitant comorbidities or significant emotional distress.

How to manage MuSK antibody-positive myasthenic crisis during pregnancy?

Myasthenia gravis (MG) is an autoimmune disease that is characterised by the formation of antibodies against acetylcholine receptors in the postsynaptic membrane of the neuromuscular junction. The course of the disease cannot be predicted during pregnancy. A subtype of MG with positive muscle-specific receptor tyrosine kinase (anti-MuSK) antibodies exhibits more localised clinical characteristics and a poor response to treatment compared with the disease subtype that involves positivity for acetylcholine receptor antibodies. Myasthenic crisis is more frequently observed in anti-MuSK-positive myasthenia patients. Anti-MuSK-positive myasthenic crisis management is very difficult and a risky situation during pregnancy. The reported case was 30 years old, female, 9 weeks pregnant and musk antibody positive. She stopped her treatment without asking her doctor because she was planning pregnancy in the 6-month period before her hospitalization. She was intubated for a long time in the intensive care unit due to myasthenic crisis and was very resistant to treatment. During this period, her pregnancy was terminated due to fetal anomaly. Plasmapheresis, IVIg and immunosuppressive treatments were applied. Our patient was discharged after a period of about 10 weeks. We share our treatment management.

Pharmacosafety of fluoroquinolone and macrolide antibiotics in the clinical care of patients with myasthenia gravis.

INTRODUCTION/AIMS: Anecdotal case reports have suggested a potential association of fluoroquinolones and macrolides with myasthenia gravis (MG) exacerbation, prompting warnings against the use of these drugs in this population. However, large-scale and reliable population-based data that demonstrate this association are lacking. This study aims to examine the association between outpatient treatment with fluoroquinolones or macrolides and MG-related hospitalization. METHODS: A retrospective cohort study consisting of adult MG patients was conducted using a large de-identified healthcare claims database. Antibiotic prescription claims were identified, and MG-related hospitalizations were assessed at 15, 30, and 90 days after the date of prescription. We used mixed effects survival regression with log-logistic distribution and independent covariance matrix to estimate odds ratios (ORs) of hospitalization for each potentially exacerbating antibiotic using beta-lactam as the reference and adjusting for covariates. RESULTS: Among 1556 MG patients receiving 894 fluoroquinolone prescriptions, 729 macrolide prescriptions, and 1608 beta-lactam prescriptions during the study period, there was no difference in 15, 30, or 90-day odds of MG-related hospitalization between fluoroquinolone or macrolide users compared to prescribed beta-lactams. However, estimates were higher for fluoroquinolones than macrolides, even after covariate adjustment (adjusted OR [aOR] 4.60, 95% confidence interval [CI] 0.55-38.57 for fluoroquinolones and OR 0.56, 95% CI 0.32-0.97 for macrolides, respectively, at 15 days). DISCUSSION: Fluoroquinolone and macrolide antibiotics are prescribed frequently to patients with MG. While statistical imprecision precludes a definitive conclusion, elevated ORs for fluoroquinolones raise the possibility of an underpowered association that merits further investigation.