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Mediastinum (Hong Kong, China) 2024Thymectomy as a management strategy for juvenile myasthenia gravis (JMG) has been increasingly adopted with the advent of minimally invasive surgical techniques. This... (Review)
Review
BACKGROUND AND OBJECTIVE
Thymectomy as a management strategy for juvenile myasthenia gravis (JMG) has been increasingly adopted with the advent of minimally invasive surgical techniques. This review evaluates existing evidence regarding the surgical management of JMG, including the benefits of surgical compared to medical therapy, important considerations when evaluating surgical candidacy and determining optimal timing of intervention. In addition, we provide an overview of the open, thoracoscopic and robotic surgical approaches available for thymectomy and compare the existing data to characterize optimal surgical management.
METHODS
A thorough literature review was conducted for full length research articles, including systematic reviews, retrospective cohort studies and case series, published between January 2000 and July 2023 regarding open, thoracoscopic or robotic thymectomy for management of JMG. Reference lists of the identified articles were manually searched for additional studies. Evidence was summarized in a narrative fashion with the incorporation of the authors' knowledge gained through clinical experience.
KEY CONTENT AND FINDINGS
Although data specific to JMG are limited to small retrospective cohort studies, available evidence supports equal to greater disease control following thymectomy versus pharmacologic management. Furthermore, outcomes may be optimized when surgery is performed earlier in the disease course, particularly for patients who are post-pubertal with generalized or severe disease and those necessitating high-dose steroid administration thereby limiting its metabolic and growth inhibitory effects. Open transsternal resection is the historic gold-standard; however, as surgeons become more comfortable with thoracoscopic and robotic-assisted thymectomy, an increasing proportion of patients are expected to undergo thymectomy. At present, the data available is unable to support conclusions regarding which surgical approach is superior; however, minimally invasive approaches may be non-inferior while offering superior cosmesis and decreased morbidity.
CONCLUSIONS
Higher-level investigation through the use of multi-institutional databases and randomized prospective trials is warranted in order to understand which child warrants thymectomy, at what point in their disease course and their development, and which surgical approach will optimize postoperative outcomes.
PubMed: 38881806
DOI: 10.21037/med-23-41 -
Mediastinum (Hong Kong, China) 2024Myasthenia gravis (MG) is a well-elucidated autoimmune disorder affecting the neuromuscular junction. Given the relationship between MG and thymic pathologies, with T... (Review)
Review
BACKGROUND AND OBJECTIVE
Myasthenia gravis (MG) is a well-elucidated autoimmune disorder affecting the neuromuscular junction. Given the relationship between MG and thymic pathologies, with T cell and antibody-mediated pathogenesis, surgical (i.e., thymectomy) and non-surgical approaches remain a mainstay of management of the disease. This review seeks to outline the involvement of the thymus in the development of lymphocytes leading to MG.
METHODS
Different databases were searched exploring the role of thymectomy in treatment and outcomes in various MG patient subpopulations, including in ocular versus generalized disease, different age groups, and antibody status.
KEY CONTENT AND FINDINGS
Overall, the findings of multiple studies and reviews provide evidence to support the efficacy and long-term success of thymectomy in the management of MG; outcomes have included remission status, symptom severity, and need for adjunctive therapy. However, the heterogeneity in the MG population suggests that there are multiple factors that may confound the results of thymectomy and still need further examination. Separately, other autoimmune diseases develop following thymectomy, and further research is required to elucidate this susceptibility. Finally, our review will discuss the different surgical approaches for thymectomy, including their advantages, limitations, and perioperative complications.
CONCLUSIONS
Overall, in light of the known pathogenesis and association of the thymus with MG, thymectomy remains an extremely effective approach for long-term management and improved clinical outcomes.
PubMed: 38881805
DOI: 10.21037/med-23-43 -
ImmunoTargets and Therapy 2024Cytokines act a vital role in autoimmune neuroinflammatory diseases (ANDs) with undetermined causal relationships. Mendelian randomization (MR) analysis was performed to...
BACKGROUND
Cytokines act a vital role in autoimmune neuroinflammatory diseases (ANDs) with undetermined causal relationships. Mendelian randomization (MR) analysis was performed to estimate the causal effects of circulating levels of cytokines on the risk of ANDs.
METHODS
The causal relationship between 34 circulating cytokines and 4 kinds of ANDs, including multiple sclerosis (MS), neuromyelitis optica (NOM), chronic inflammatory demyelinating polyneuropathy (CIDP) and myasthenia gravis (MG) were explored using four methods of MR analysis. MR-PRESSO, MR-Egger regression methods and Cochran's Q statistic were utilized to identify the instrumental variables (IVs) with potential pleiotropy and heterogeneity. The Bonferroni correction was used for multiple group comparisons. -value less than 3.68E-04 (0.05/ (34*4)) was considered statistically significant.
RESULTS
Negative causal effects of circulating levels of interleukin (IL)-8 (OR = 0.648, 95% CI: 0.494-0.851, = 0.002) on risk of MS, chemokine (C-C Motif) ligand (CCL)-5 (OR = 0.295, 95% CI: 0.103-0.841, = 0.022) and stem cell growth factor-beta (SCGF-β) (OR = 0.745, 95% CI: 0.565-0.984, = 0.038) on risk of CIDP, as well as positive causal effects of circulating levels of IL-2 receptor α (IL-2Rα) (OR = 1.216, 95% CI: 1.120-1.320, = 3.20E-06) and chemokine C-X-C motif ligand (CXCL)-10 (OR = 1.404, 95% CI: 1.094-1.803, = 0.008) on MS were observed. Nevertheless, only IL-2Rα still had a causal effect on MS after Bonferroni correction.
CONCLUSION
The results identify a genetically predicted causal effect of IL-2Rα, IL-8 and CXCL-10 on MS, CCL-5 and SCGF-β on CIDP.
PubMed: 38881648
DOI: 10.2147/ITT.S456326 -
Frontiers in Neurology 2024The pattern of extraocular muscle involvement in ocular myasthenia gravis varies across different reports, diverging from our own observations. Thus, we employed two...
Investigation of the differential susceptibility of extraocular muscles in patients diagnosed with ocular myasthenia gravis based on the computerized diplopia test and the Ocular Motor Nerve Palsy Scale.
INTRODUCTION
The pattern of extraocular muscle involvement in ocular myasthenia gravis varies across different reports, diverging from our own observations. Thus, we employed two novel tools to discern this pattern.
METHODS
A retrospective analysis was conducted to collect and organize clinical data from 43 patients diagnosed with ocular myasthenia gravis. Each patient underwent both the computerized diplopia test and the Ocular Motor Nerve Palsy Scale assessment to evaluate the involvement of extraocular muscles.
RESULTS
Among the patients, there were 30 male and 13 female individuals, with a total of 113 affected extraocular muscles identified. Among all the affected extraocular muscles, the involvement of the levator palpebrae superioris muscle accounted for 35.40%, medial rectus muscle 7.7%, lateral rectus muscle 16.81%, superior rectus muscle 13.27%, inferior rectus muscle 12.39%, superior oblique muscle 1.77%, and inferior oblique muscle 2.65% of the total affected extraocular muscles. The positivity rates of the Neostigmine test were 89.19%, AChR antibody detection was 59.38%, and repetitive nerve stimulation was 34.38%. The AChR antibody positive rate among patients with only diplopia was 100%; among those with only ptosis, it was 80%; and among those with both diplopia and ptosis, it was 86.67%.
CONCLUSION
The involvement of the extraocular muscles is not uniform. The levator palpebrae superioris exhibits the highest incidence rate, followed by the four rectus muscles and two oblique muscles. The inferior oblique involvement typically occurs when four or more EOMs are affected. Moreover, the levator palpebrae superioris and medial rectus show a higher tendency for bilateral involvement compared with other extraocular muscles.
PubMed: 38872815
DOI: 10.3389/fneur.2024.1353248 -
Neuromuscular Disorders : NMD Jun 2024Decreased cough strength in myasthenia gravis (MG) leads to aspiration and increases the risk of MG crisis. The aim of this study was to clarify the reliability and...
Decreased cough strength in myasthenia gravis (MG) leads to aspiration and increases the risk of MG crisis. The aim of this study was to clarify the reliability and validity of cough peak flow (CPF) measurements in MG. A total of 26 patients with MG who underwent CPF measurements using the peak flow meter by themselves were included. MG symptoms were evaluated by pulmonary function tests and clinical MG assessment scales before and after immune-treatments. The relationship between CPF and pulmonary function tests and MG comprehensive were assessed. The cut-off value of CPF for aspiration risk was determined and the area under the curve (AUC) was calculated. The intraclass correlation coefficient was more than 0.95 for pre-and post-treatment. Positive correlations were found between CPF and almost all spirometric values as well as between the differences of pre-and post-treatment in CPF and quantitative myasthenia gravis score. The CPF for identifying the aspiration risk was used to calculate the CPF cut-off value of 205 L/min with a sensitivity of 0.77, specificity of 0.90, and AUC of 0.85. The CPF, a convenient measure by patients themselves, has a high reliability in patients with MG, and is a useful biomarker reflecting MG symptoms.
PubMed: 38870650
DOI: 10.1016/j.nmd.2024.06.003 -
Cureus May 2024A myasthenic crisis denotes a severe exacerbation of myasthenia gravis, leading a patient to enter a life-threatening state due to progressing muscle weakness that...
A myasthenic crisis denotes a severe exacerbation of myasthenia gravis, leading a patient to enter a life-threatening state due to progressing muscle weakness that ultimately results in respiratory failure. A crisis can require intubation, mechanical ventilation, and additional critical care to prevent further decompensation and potentially death. Numerous well-documented precipitating factors exist, such as infections, surgery, stress, and various medications. We present the case of a 43-year-old woman recently diagnosed with myasthenia gravis who has experienced two myasthenic crises since diagnosis without evident triggers such as surgery, changes in medication, or infection. Following an unremarkable initial diagnostic test and continued treatment for the crisis, we sought additional information from the patient's family member at the bedside. We were informed that two weeks prior to both times of crisis with intubation, the patient had dyed her hair blue. The common chemical component in the two different hair dyes used was methylisothiazolinone, which is suspected to have contributed to the exacerbation of the patient's myasthenia gravis. As more evidence for new precipitating factors of myasthenic crises develops, it is crucial for physicians to quickly identify signs and symptoms of a crisis so appropriate intervention can occur in a time-sensitive manner. In addition, myasthenia gravis patients should be made aware to be cautious of precipitating factors of a crisis, including but not limited to new beauty products.
PubMed: 38868287
DOI: 10.7759/cureus.60186 -
Clinical Case Reports Jun 2024Immune checkpoint inhibitors can rarely lead to occurrence of myositis, myocarditis, and myasthenia gravis (MG). Early recognition and multidisciplinary management are...
KEY CLINICAL MESSAGE
Immune checkpoint inhibitors can rarely lead to occurrence of myositis, myocarditis, and myasthenia gravis (MG). Early recognition and multidisciplinary management are crucial for optimal outcomes. Vigilance for overlapping toxicities is essential in patients receiving combination immunotherapy.
ABSTRACT
The use of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, but it is associated with immune-related adverse events (IRAEs) affecting various organ systems. The simultaneous occurrence of MG, myocarditis, and myositis highlights the complex nature of IRAEs. Early recognition and comprehensive multidisciplinary management are crucial for optimal patient outcomes. We present a unique case report of a 76-year-old male patient with advanced melanoma who developed concurrent myositis, myocarditis, and MG while receiving combination immunotherapy with Nivolumab and Ipilimumab. This case underscores the significance of recognizing and addressing the "Terrible Triad" of IRAEs in patients receiving ICIs. Healthcare providers should maintain a high index of suspicion for overlapping toxicities and promptly initiate appropriate interventions.
PubMed: 38863868
DOI: 10.1002/ccr3.8968 -
Frontiers in Neurology 2024Our aim was to translate, adapt and validate the Myasthenia Gravis Activities of Daily Living scale into the Latvian language and to evaluate this instrument (MG-ADL-L)...
INTRODUCTION
Our aim was to translate, adapt and validate the Myasthenia Gravis Activities of Daily Living scale into the Latvian language and to evaluate this instrument (MG-ADL-L) in terms of construct validity and reliability.
METHODS
We enrolled patients with a confirmed MG diagnosis, who could speak Latvian fluently. We performed translation and adaptation according to the cross-cultural adaptation guidelines for self-reported measures. The patients were evaluated by a physician according to the Myasthenia Gravis Foundation of America classification (MGFA) and using the Myasthenia Gravis Composite Score (MGCS). Patients were asked to complete the MG-ADL-L and the 15-item Myasthenia Gravis Quality of Life (MGQOL15) Internal consistency was evaluated based on Cronbach's α, reproducibility-Cohen's weighted kappa and construct validity-Spearman's correlation between the MG-ADL-L and the MGQOL15 and MGCS. We used the Kruskal-Wallis H test to compare the MG-ADL-L score distribution between the MGFA groups.
RESULTS
38 enrolled patients in the study. There was an acceptable internal consistency (Cronbach's α = 0.76) and moderate to very good agreement between the test and retest scores (Cohen's weighted kappa = 0.54 and 0.81). The MG-ADL-L showed a moderate positive correlation with the MGQOL15 (r = 0.5, = 0.001) and the MGCS (r = 0.62, < 0.001). There was a significant difference in MG-ADL-L scores between the MGFA groups ( = 0.007).
DISCUSSION
The MG-ADL-L is a valid and reliable self-reported scale to assess and evaluate symptom severity and the impact of the disease on the lives of patients with MG.
PubMed: 38859974
DOI: 10.3389/fneur.2024.1397603 -
Cureus May 2024The widespread use of immune checkpoint inhibitors (ICIs) for the treatment of various types of cancer has led to increasing reports of associated adverse effects. The...
The widespread use of immune checkpoint inhibitors (ICIs) for the treatment of various types of cancer has led to increasing reports of associated adverse effects. The use of the ipilimumab/nivolumab/sacituzumab combination is currently under study in patients with metastatic urothelial carcinoma, given their potential synergism for immunogenic cell death. Information regarding the toxicity spectrum of this combination is lacking. Here, we describe a patient with urothelial carcinoma who had a severe multisystem autoimmune-like toxicity and myasthenia gravis-like syndrome in response to the ipilimumab/nivolumab/sacituzumab combination therapy. We also briefly describe the literature regarding the association between combined immunotherapy use and systemic and neurological autoimmunity.
PubMed: 38854361
DOI: 10.7759/cureus.60003 -
BMC Neurology Jun 2024Myasthenia gravis (MG) is a long-term autoimmune disorder that affects the neuromuscular junction, causing muscle weakness and fatigue as its primary clinical features....
BACKGROUND
Myasthenia gravis (MG) is a long-term autoimmune disorder that affects the neuromuscular junction, causing muscle weakness and fatigue as its primary clinical features. Vitamin D is crucial for both the autoimmune response and skeletal muscle function.
CASE PRESENTATION
Here, we presented a case report documenting the substantial improvement in symptoms experienced by a patient who underwent subtotal gastrectomy for gastric cancer following high-dose Vitamin D supplementation. The patient developed generalized MG two months after the surgery and did not respond adequately to pyridostigmine therapy, experiencing a progressive deterioration of the condition. A significant reduction in vitamin D concentration was observed following subtotal gastrectomy. In response, high-dose vitamin D supplementation was administered to the patient. Within one week of treatment, swallowing symptoms improved, enabling the consumption of a small amount of liquid food. By the second week, substantial swallowing and neck function improvements were evident. After one month, the patient regained the ability to straighten the neck while walking and consumed a regular diet despite persistent difficulties chewing hard food.
CONCLUSIONS
This case underscores the therapeutic potential of vitamin D in alleviating MG symptoms, particularly in individuals with compromised vitamin D levels following gastrectomy. The observed improvements present a new perspective on the possible involvement of vitamin D supplementation in the management of postoperative MG cases.
Topics: Humans; Gastrectomy; Myasthenia Gravis; Vitamin D; Stomach Neoplasms; Male; Female; Aged; Middle Aged; Dietary Supplements
PubMed: 38840065
DOI: 10.1186/s12883-024-03687-z