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Proceedings of the National Academy of... Jun 2024Treatment with autologous chimeric antigen receptor (CAR) T cells has emerged as a highly effective approach in neuroimmunological disorders such as myasthenia gravis....
Treatment with autologous chimeric antigen receptor (CAR) T cells has emerged as a highly effective approach in neuroimmunological disorders such as myasthenia gravis. We report a case of successful anti-CD19 CAR T cell use in treatment-refractory stiff-person syndrome (SPS). To investigate clinical and immunological effects of anti-CD19 CAR T cell use in treatment-refractory SPS, a 69-y-old female with a 9-y history of treatment-refractory SPS with deteriorating episodes of stiffness received an infusion of autologous anti-CD19 CAR T cells (KYV-101) and was monitored clinically and immunologically for more than 6 mo. CAR T cell infusion resulted in reduced leg stiffness, drastic improvement in gait, walking speed increase over 100%, and daily walking distance improvement from less than 50 m to over 6 km within 3 mo. GABAergic medication (benzodiazepines) was reduced by 40%. KYV-101 CAR T cells were well tolerated with only low-grade cytokine release syndrome. This report of successful use of anti-CD19 CAR T cells in treatment-refractory SPS supports continued exploration of this approach in SPS and other B cell-related autoimmune disorders.
Topics: Humans; Stiff-Person Syndrome; Female; Aged; Immunotherapy, Adoptive; Antigens, CD19; Receptors, Chimeric Antigen; T-Lymphocytes; Treatment Outcome
PubMed: 38885382
DOI: 10.1073/pnas.2403227121 -
Clinical Case Reports Jun 2024The co-occurrence of myasthenia gravis (MG) and lichen planus (LP) is a rare phenomenon, with only 13 cases reported in the English literature between 1971 and 2024....
KEY CLINICAL MESSAGE
The co-occurrence of myasthenia gravis (MG) and lichen planus (LP) is a rare phenomenon, with only 13 cases reported in the English literature between 1971 and 2024. Patients with MG or LP, regardless of the thymoma status, require close monitoring for other autoimmune diseases.
ABSTRACT
Myasthenia gravis (MG) is an uncommon autoimmune disease, resulting in fatigable muscle weakness in the ocular, bulbar, and respiratory muscles, as well as muscles of the extremities. Lichen planus (LP) is an autoimmune mucocutaneous disease, presenting with pruritic and violaceous plaques on the skin and mucosal surfaces. So far, MG and LP co-occurrence is only reported in anecdotal individuals. This study reports a patient with MG and LP and systematically reviews the English literature on this rare co-occurrence from 1971 to 2024, indicating only 13 cases with similar conditions. A 67-year-old man presented with ocular and progressive bulbar symptoms, a year after being diagnosed with generalized LP. Laboratory evaluations were normal except for the high anti-AchR-Ab titer and a positive ANA titer. Neurologic examinations revealed asymmetric bilateral ptosis, weakness and fatigability in proximal muscles, and a severe reduction in the gag reflex. He was diagnosed with late-onset, seropositive MG. The treatment included pyridostigmine (60 mg, three times daily), intravenous immunoglobulin (25 g daily for 5 days), and oral prednisolone. There was no evidence of thymoma in the chest x-ray and CT scan without contrast. However, a CT scan with contrast was not performed due to the patient's unstable condition. A common autoimmune mechanism may underlie the unclear pathophysiology of MG and LP co-occurrence, with or without thymoma. Patients with MG, LP, or thymoma require close monitoring and assessment for other possible autoimmune diseases.
PubMed: 38883218
DOI: 10.1002/ccr3.9065 -
Cureus May 2024Myasthenia gravis (MG) is a rare disorder that most commonly presents with ocular symptoms. Despite the highly sensitive blood work that can be used to diagnose the...
Myasthenia gravis (MG) is a rare disorder that most commonly presents with ocular symptoms. Despite the highly sensitive blood work that can be used to diagnose the disease, it is frequently misdiagnosed until the disease becomes systemic. Literature, however, shows that those who begin treatment with acetylcholinesterase inhibitors before systemic presentation have a better prognosis. We discuss the case of a patient who presented to the clinic with a chief complaint of diplopia that was subsequently referred to ophthalmology. It was not until lab work was done by a subspecialist that the diagnosis of MG was made. The patient quickly responded to an acetylcholinesterase inhibitor and has since had a great prognosis. Here, we are advocating for the inclusion of routine lab work in the evaluation of patients who present to the primary care setting with diplopia in the absence of red flag symptoms. This approach aids in deciphering the potential involvement of MG in diplopia or ptosis. While such symptoms justify referral to ophthalmology, logistical challenges often hinder a prompt evaluation. Early diagnosis with the incorporation of routine lab work offers the potential to expedite the diagnosis of a rare disease. In doing so, providers can improve prognosis and potentially mitigate additive medical consultations.
PubMed: 38882969
DOI: 10.7759/cureus.60521 -
Frontiers in Pharmacology 2024Myasthenia gravis (MG) is an antibody-mediated autoimmune disease with a prevalence of 150-250 cases per million individuals. Autoantibodies include long-lived... (Review)
Review
Myasthenia gravis (MG) is an antibody-mediated autoimmune disease with a prevalence of 150-250 cases per million individuals. Autoantibodies include long-lived antibodies against the acetylcholine receptor (AChR), mainly of the IgG1 subclass, and IgG4, produced almost exclusively by short-lived plasmablasts, which are prevalent in muscle-specific tyrosine kinase (MuSK) myasthenia gravis. Numerous investigations have demonstrated that MG patients receiving conventional medication today still do not possess satisfactory symptom control, indicating a substantial disease burden. Subsequently, based on the type of the autoantibody and the pathogenesis, we synthesized the published material to date and reached a conclusion regarding the literature related to personalized targeted therapy for MG. Novel agents for AChR MG have shown their efficacy in clinical research, such as complement inhibitors, FcRn receptor antagonists, and B-cell activating factor (BAFF) inhibitors. Rituximab, a representative drug of anti-CD20 therapy, has demonstrated benefits in treatment of MuSK MG patients. Due to the existence of low-affinity antibodies or unidentified antibodies that are inaccessible by existing methods, the treatment for seronegative MG remains complicated; thus, special testing and therapy considerations are necessary. It may be advantageous to initiate the application of novel biologicals at an early stage of the disease. Currently, therapies can also be combined and individualized according to different types of antibodies. With such a wide range of drugs, how to tailor treatment strategies to patients with various conditions and find the most suitable solution for each MG profile are our necessary and urgent aims.
PubMed: 38881870
DOI: 10.3389/fphar.2024.1370411 -
Mediastinum (Hong Kong, China) 2024Thymectomy with median sternotomy is the gold standard for thymoma and myasthenia gravis, although minimally invasive procedures such as robot-assisted surgery have... (Review)
Review
BACKGROUND AND OBJECTIVE
Thymectomy with median sternotomy is the gold standard for thymoma and myasthenia gravis, although minimally invasive procedures such as robot-assisted surgery have recently become more common. However, the superiority of these approaches has not been established, and they are infrequently recommended for localized lesions. The International Thymic Malignancies Interest Group warned that despite the perceived reduction in length of hospital stay and pain, the benefits of these approaches compared to the open approach have not been fully substantiated and that prospective collaborative data collection is critical in defining the value of these techniques. Whether thymectomy is necessary for stage I thymomas in the absence of myasthenia gravis or anti-acetylcholine receptor antibodies is also unclear. This study reviews and discusses the literature on this subject.
METHODS
A narrative review was conducted using PubMed and Scopus databases. Original research articles comparing robotic to video-assisted thoracic surgery or to open thymectomy for thymomas were included. A comparison of partial resection and total thymectomy (thymothymectomy) for thymomas was also conducted.
KEY CONTENT AND FINDINGS
Perioperative outcomes such as blood loss, operative duration, complications, and length of hospital stay were better for robot-assisted resection of early-stage thymomas than for open thymoma surgery. It would be premature to consider partial resection as an appropriate treatment option for thymomas.
CONCLUSIONS
Robotic thymothymectomy is safe with effective and promising long-term results and oncological and surgical outcomes in patients with thymoma. Robotic thymectomy can become the standard procedure in patients with early-stage thymomas.
PubMed: 38881811
DOI: 10.21037/med-23-37 -
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