Acupuncture and moxibustion treatment for myasthenia gravis: A systematic review and meta-analysis.

BACKGROUND: Myasthenia gravis (MG) is a common autoimmune disease that often involves the skeletal muscle of the whole body and seriously affects patients' quality of life. Acupuncture and moxibustion treatment of MG has unique advantages, the aim is to evaluate the clinical effect of acupuncture and moxibustion on MG. METHODS: The literature on acupuncture and moxibustion treating MG in PubMed, CochraneLibrary, EMBASE, SCI, China Academic Journals full-text database, China Biology Medicine disc, VIP and Wanfang database were searched through computers from the establishment of the database to December 2022. RESULTS: A total of 11 studies were included, involving 658 patients, where 330 in the treatment group and 328 in the control group. The results of the meta-analysis showed that the treatment group performed better than the control group in improving the total clinical response rate (OR = 3.26, 95%[2.04,5.21], P < .01). Additionally, the treatment group outperformed the control group in raising the absolute clinical score (MD = -3.48, 95%CI[-5.17, -1.78], P < .01). However, there was no significant difference between the treatment group and the control group in improving the level of serum interleukin-6 receptor (MD = -1.45,95%CI[-6.85,3.95], P > .05) and OMG quantitative score (MD = -2.16,95%CI[-4.85,0.52], P > .05). The total clinical effective rate was tested for publication bias, which showed that the 2 sides of the funnel plot were asymmetrical, suggesting the possible existence of publication bias. CONCLUSION: Acupuncture and moxibustion has a good effect on MG, which is better than conventional Western medicine in improving the total clinical effective rate and absolute clinical score.

[AChR Antibody-Positive Myasthenia Gravis].

Herein, we describe the mechanisms, diagnostic procedures, and treatment options for acetylcholine receptor (AChR) antibody-positive myasthenia gravis (MG). The upstream pathomechanism of this condition involves AChR-sensitized T cell-dependent B cell proliferation and the subsequent production of pathogenic autoantibodies. Downstream molecules include AChR antibodies that activate complement pathways, resulting in the destruction of motor endplates. We further introduce newly-developed molecular targeted drugs for the treatment of MG that aims to secure patients' health-related quality of life.

[Muscle-Specific Receptor Tyrosine Kinase Antibody Positive Myasthenia Gravis].

Reportedly, patients with muscle-specific kinase (MuSK) antibody-positive myasthenia gravis (MG) account for approximately 3.0% of all patients with MG in Japan. Compared with patients who have acetylcholine receptor antibody-positive MG, those with MuSK antibody-positive MG show young-onset disease with female predominance, a low rate of ocular involvement (5.9%), and greater severity of dysphagia. The aforementioned types of MG are indistinguishable based on clinical symptoms and electrophysiological tests, and measurement of MuSK antibodies is essential for diagnosis. Thymectomy and complement inhibitors are not indicated for treatment, and acetylcholinesterase inhibitors, steroids, immunosuppressants, plasma exchange, intravenous immunoglobulin therapy, and neonatal Fc receptor inhibitors are used.

The intricate dance of non-coding RNAs in myasthenia gravis pathogenesis and treatment.

Myasthenia gravis (MG) stands as a perplexing autoimmune disorder affecting the neuromuscular junction, driven by a multitude of antibodies targeting postsynaptic elements. However, the mystery of MG pathogenesis has yet to be completely uncovered, and its heterogeneity also challenges diagnosis and treatment. Growing evidence shows the differential expression of non-coding RNAs (ncRNAs) in MG has played an essential role in the development of MG in recent years. Remarkably, these aberrantly expressed ncRNAs exhibit distinct profiles within diverse clinical subgroups and among patients harboring various antibody types. Furthermore, they have been implicated in orchestrating the production of inflammatory cytokines, perturbing the equilibrium of T helper 1 cells (Th1), T helper 17 cells (Th17), and regulatory T cells (Tregs), and inciting B cells to generate antibodies. Studies have elucidated that certain ncRNAs mirror the clinical severity of MG, while others may hold therapeutic significance, showcasing a propensity to return to normal levels following appropriate treatments or potentially foretelling the responsiveness to immunosuppressive therapies. Notably, the intricate interplay among these ncRNAs does not follow a linear trajectory but rather assembles into a complex network, with competing endogenous RNA (ceRNA) emerging as a prominent hub in some cases. This comprehensive review consolidates the landscape of dysregulated ncRNAs in MG, briefly delineating their pivotal role in MG pathogenesis. Furthermore, it explores their promise as prospective biomarkers, aiding in the elucidation of disease subtypes, assessment of disease severity, monitoring therapeutic responses, and as novel therapeutic targets.

[Myasthenia Gravis - Update]. / Myasthenia gravis ­ Update.

Myasthenia gravis - still a challenge for sufferers and doctors in 2023. But which therapy is best suited? Our clinically experienced experts have summarized the current guidelines for diagnosis and treatment in order to provide optimal support for those affected. Find out how you can carry out a quick and targeted diagnosis and which treatment options are available to alleviate the course of the disease.

[Novel immunomodulatory therapies in myasthenia gravis]. / Myasthénie grave : nouvelles thérapies immunosuppressives.

Myasthenia gravis (MG) is an autoimmune disease characterized by fluctuating weakness of skeletal muscles. Despite current treatments, a significant percentage of patients remain symptomatic. This review explores new immunosuppressive therapies and ongoing clinical trials in MG, including depletion of B lymphocytes with agents such as rituximab and inebilizumab, as well as the use of eculizumab, efgartigimod, satralizumab, tocilizumab, and CAR-T (Chimeric Antigen Receptor-T) cell therapy. These advancements aim to improve disease control and patients' quality of life.

La myasthénie grave (MG) est une maladie auto-immune caractérisée par une faiblesse fluctuante des muscles squelettiques. Malgré les traitements classiques, un pourcentage significatif de patients reste symptomatique. Cet article explore les nouvelles thérapies immunosuppressives et les essais cliniques en cours pour la MG, notamment la déplétion des lymphocytes B avec des agents tels que le rituximab et l'inébilizumab, ainsi que l'utilisation de l'éculizumab, de l'efgartigimod, du satralizumab, du tocilizumab et de la thérapie par cellules CAR-T (Chimeric Antigen Receptor-T). Ces avancées visent à améliorer le contrôle de la maladie et la qualité de vie des patients.

Promising therapies for the treatment of myasthenia gravis.

INTRODUCTION: Myasthenia gravis (MG) is an autoimmune condition targeting the neuromuscular junction, which manifests with neuromuscular symptoms of varying severity and significant morbidity. The mainstay of treatment in MG is mitigation of the immune cascade with steroids and non-steroidal immunosuppressive therapies. The therapeutic strategies in MG are transitioning from broad and indiscriminate immunosuppression to novel agents targeting key steps in MG pathogenesis, including T cell activation, B cell proliferation, complement activation, maintenance of pathogenic antibody production, and proinflammatory cytokine production. AREAS COVERED: In this review, an overview of the pathogenesis of MG and traditional MG therapies is presented, followed by a discussion of the novel MG drugs that have been evaluated in phase 3 clinical trials with an emphasis on those which have received regulatory approval. EXPERT OPINION: Novel MG therapeutics belonging to the classes of complement inhibitors, neonatal Fc receptor (FcRn) inhibitors and B cell depletors, as well as the other emerging MG drugs in the pipeline constitute promising treatment strategies with potentially better efficacy and safety compared to the conventional MG treatments. However, further long-term research is needed in order to optimize the implementation of these new treatment options for the appropriate patient populations.

Myasthenia gravis-Pathophysiology, diagnosis, and treatment.

Myasthenia gravis (MG) is an autoimmune disease characterized by dysfunction of the neuromuscular junction resulting in skeletal muscle weakness. It is equally prevalent in males and females, but debuts at a younger age in females and at an older age in males. Ptosis, diplopia, facial bulbar weakness, and limb weakness are the most common symptoms. MG can be classified based on the presence of serum autoantibodies. Acetylcholine receptor (AChR) antibodies are found in 80%-85% of patients, muscle-specific kinase (MuSK) antibodies in 5%-8%, and <1% may have low-density lipoprotein receptor-related protein 4 (Lrp4) antibodies. Approximately 10% of patients are seronegative for antibodies binding the known disease-related antigens. In patients with AChR MG, 10%-20% have a thymoma, which is usually detected at the onset of the disease. Important differences between clinical presentation, treatment responsiveness, and disease mechanisms have been observed between these different serologic MG classes. Besides the typical clinical features and serologic testing, the diagnosis can be established with additional tests, including repetitive nerve stimulation, single fiber EMG, and the ice pack test. Treatment options for MG consist of symptomatic treatment (such as pyridostigmine), immunosuppressive treatment, or thymectomy. Despite the treatment with symptomatic drugs, steroid-sparing immunosuppressants, intravenous immunoglobulins, plasmapheresis, and thymectomy, a large proportion of patients remain chronically dependent on corticosteroids (CS). In the past decade, the number of treatment options for MG has considerably increased. Advances in the understanding of the pathophysiology have led to new treatment options targeting B or T cells, the complement cascade, the neonatal Fc receptor or cytokines. In the future, these new treatments are likely to reduce the chronic use of CS, diminish side effects, and decrease the number of patients with refractory disease.

Current state of research on exercise for the treatment of myasthenia gravis: A scoping review.

OBJECTIVE: To provide a comprehensive overview of existing evidence, research gaps, and future research priorities concerning the treatment of myasthenia gravis (MG) using exercise therapies. METHOD: Clinical studies on exercise treatment for MG were searched in nine databases to conduct a scoping review. Two independent researchers screened the literature and comprehensively analyzed the characteristics and limitations of the included articles. RESULTS: A total of 5725 studies were retrieved, of which 24 were included. The included studies were conducted in 16 different countries/regions and 456 patients were enrolled. Study designs included both interventional and observational studies. Exercise interventions included aerobic exercise, resistance exercise, balance training, and stretch training, and are typically administered in conjunction with medication, usual care, or some other interventions. The intensity, frequency, and duration of exercise interventions varied hugely among studies. Six-minute walk test, adverse events, muscle strength, MG quality of life-15 scale, forced vital capacity, quantitative MG scale, and MG activities of daily living scale were the most frequently used outcomes. All studies reported results in favor of the efficacy and safety of exercise in MG, and exercise-related adverse events were reported in two studies. CONCLUSION: This scoping review provides an overview of the evidence concerning exercise treatment for MG. Key gaps in evidence include a limited number of participants, complex interventions, variability in outcome selection, and insufficient reporting in publications. The promotion of exercise treatment for MG still encounters several obstacles. A larger population, rigorous study design and conduction, standardized interventions and outcomes, and standardized reporting are essential.

[Myasthenia gravis-Gender aspects and family planning]. / Myasthenia gravis ­ Genderaspekte und Familienplanung.

BACKGROUND: There is evidence that gender-specific differences can influence the diagnostics, treatment and long-term disease course of myasthenia gravis (MG). In women the diagnosis is often made during childbearing age. OBJECTIVE: Gender-specific differences in MG and relevant aspects in routine clinical practice are presented. In addition, current studies on family planning, pregnancy and childbirth in MG are highlighted and treatment recommendations are derived. MATERIAL AND METHODS: Narrative literature review. RESULTS: In addition to sociodemographic data, gender-specific differences encompass clinical as well as paraclinical factors, such as disease severity and antibody status. With few exceptions pregnancy is possible with good maternal and neonatal outcome. During pregnancy and peripartum, children of MG patients should be closely monitored for early detection and treatment of potential syndromes caused by diaplacental transfer of maternal antibodies. CONCLUSION: Gender-specific factors can influence the course of MG. Adequate medical counselling and multidisciplinary collaboration are essential for MG patients who wish to have children.

B cell lineage reconstitution underlies CAR-T cell therapeutic efficacy in patients with refractory myasthenia gravis.

B-cell maturation antigen (BCMA), expressed in plasmablasts and plasma cells, could serve as a promising therapeutic target for autoimmune diseases. We reported here chimeric antigen receptor (CAR) T cells targeting BCMA in two patients with highly relapsed and refractory myasthenia gravis (one with AChR-IgG, and one with MuSk-IgG). Both patients exhibited favorable safety profiles and persistent clinical improvements over 18 months. Reconstitution of B-cell lineages with sustained reduced pathogenic autoantibodies might underlie the therapeutic efficacy. To identify the possible mechanisms underlying the therapeutic efficacy of CAR-T cells in these patients, longitudinal single-cell RNA and TCR sequencing was conducted on serial blood samples post infusion as well as their matching infusion products. By tracking the temporal evolution of CAR-T phenotypes, we demonstrated that proliferating cytotoxic-like CD8 clones were the main effectors in autoimmunity, whereas compromised cytotoxic and proliferation signature and profound mitochondrial dysfunction in CD8+ Te cells before infusion and subsequently defect CAR-T cells after manufacture might explain their characteristics in these patients. Our findings may guide future studies to improve CAR T-cell immunotherapy in autoimmune diseases.

Thymoma-associated autoimmune encephalitis with myasthenia gravis: Case series and literature review.

OBJECTIVES: This comprehensive review aimed to compile cases of patients with thymoma diagnosed with both autoimmune encephalitis (AE) and myasthenia gravis (MG), and describe their clinical characteristics. METHODS: Clinical records of 3 AE patients in the first affiliated hospital of Sun Yat-sen University were reviewed. All of them were diagnosed with AE between 1 November 2021 and 1 March 2022, and clinical evidence about thymoma and MG was found. All published case reports were searched for comprehensive literature from January 1990 to June 2022. RESULTS: A total of 18 cases diagnosed with thymoma-associated autoimmune encephalitis (TAAE) and thymoma-associated myasthenia gravis (TAMG) were included in this complication, wherein 3 cases were in the first affiliated hospital of Sun Yat-sen University and the other 15 were published case reports. 5/18 patients had alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antibody (AMPAR-Ab) in their serum and cerebrospinal fluid (CSF). All of them had positive anti-acetylcholine receptor antibody (AChR-Ab). And 12/18 patients showed a positive response to thymectomy and immunotherapy. Besides, thymoma recurrences were detected because of AE onset. And the shortest interval between operation and AE onset was 2 years in patients with thymoma recurrence. CONCLUSIONS: There was no significant difference in the clinical manifestations between these patients and others with only TAMG or TAAE. TAAE was commonly associated with AMPAR2-Ab. Significantly, AE more commonly heralded thymoma recurrences than MG onset. And the intervals of thymectomy and MG or AE onset had different meanings for thymoma recurrence and prognoses of patients.

Peripheral nervous system and neuromuscular disorders in the emergency department: A review.

INTRODUCTION: Acute presentations and emergencies in neuromuscular disorders (NMDs) often challenge clinical acumen. The objective of this review is to refine the reader's approach to history taking, clinical localization and early diagnosis, as well as emergency management of neuromuscular emergencies. METHODS: An extensive literature search was performed to identify relevant studies. We prioritized meta-analysis, systematic reviews, and position statements where possible to inform any recommendations. SUMMARY: The spectrum of clinical presentations and etiologies ranges from neurotoxic envenomation or infection to autoimmune disease such as Guillain-Barré Syndrome (GBS) and myasthenia gravis (MG). Delayed diagnosis is not uncommon when presentations occur "de novo," respiratory failure is dominant or isolated, or in the case of atypical scenarios such as GBS variants, severe autonomic dysfunction, or rhabdomyolysis. Diseases of the central nervous system, systemic and musculoskeletal disorders can mimic presentations in neuromuscular disorders. CONCLUSIONS: Fortunately, early diagnosis and management can improve prognosis. This article provides a comprehensive review of acute presentations in neuromuscular disorders relevant for the emergency physician.

The epidemiology and societal costs of myasthenia gravis in Norway: A non-interventional study using national registry data.

BACKGROUND AND PURPOSE: With the emergence of new treatment options for myasthenia gravis (MG), there is a need for information regarding epidemiology, healthcare utilization, and societal costs to support economic evaluation and identify eligible patients. We aimed to enhance the understanding of these factors using nationwide systematic registry data in Norway. METHODS: We received comprehensive national registry data from five Norwegian health- and work-related registries. The annual incidence and prevalence were estimated for the period 2013-2021 using nationwide hospital and prescription data. The direct, indirect (productivity losses) and intangible costs (value of lost life-years [LLY] and health-related quality of life [HRQoL]) related to MG were estimated over a period of 1 year. RESULTS: In 2021, the incidence of MG ranged from 15 to 16 cases per year per million population depending on the registry used, while the prevalence varied between 208.9 and 210.3 per million population. The total annual societal costs of MG amounted to EUR 24,743 per patient, of which EUR 3592 (14.5%) were direct costs, EUR 8666 (35.0%) were productivity loss, and EUR 12,485 (50.5%) were lost value from LLY and reduced HRQoL. CONCLUSION: The incidence and prevalence of MG are higher than previously estimated, and the total societal costs of MG are substantial. Our findings demonstrate that productivity losses, and the value of LLY and HRQoL constitute a considerable proportion of the total societal costs.

Systematic review of the patient burden of generalised myasthenia gravis in Europe, the Middle East, and Africa.

BACKGROUND: Myasthenia gravis (MG) is a rare autoimmune disease characterised by muscle weakness, and progression from ocular (oMG) to generalised (gMG) symptoms results in a substantial negative impact on quality of life (QoL). This systematic review aimed to provide an overview of the patient burden experienced by people living with gMG. METHODS: Electronic database searches (conducted March 2022), supplemented by interrogation of grey literature, were conducted to identify studies reporting patient burden outcomes in patients with gMG in Europe, the Middle East and Africa. Results were synthesised narratively due to the heterogeneity across trials. RESULTS: In total, 39 patient burden publications (representing 38 unique studies) were identified as relevant for inclusion in the systematic review, consisting of 37 publications reporting formal patient-reported outcome measures (PROMs), and two publications describing alternative qualitative assessments of patient experience. The studies included a variety of measures including generic and disease-specific PROMs, as well as symptom-specific PROMs focusing on key comorbidities including depression, anxiety, fatigue and sleep disturbance. The findings showed some variation across studies and PROMs; however, in general there was evidence for worse QoL in patients with gMG than in healthy controls or in patients with oMG, and a trend for worsening QoL with increasing MG severity. CONCLUSIONS: This review highlights the importance of considering patient QoL when developing and assessing treatment and management plans for patients with gMG. However, the heterogeneity identified across studies illustrates the need for further representative and well-powered studies in large cohorts administering consistent, validated questionnaires. TRIAL REGISTRATION: The protocol for this systematic review was registered in PROSPERO: CRD42022328444.

[Clinical Features of Myasthenia Gravis as an Immune-related Adverse Event].

Neurological and muscular immune-related adverse events (irAEs) associated with cancer treatment using immune checkpoint inhibitors (ICIs) may show a diverse clinical presentation. Myasthenia gravis (MG) represents a serious irAE associated with the aforementioned therapy. Recent studies have discussed the clinical features of MG that occurs as an irAE (irAE-MG). The incidence of irAE-MG is estimated to be 1%. This complication occurs during the early phase of ICI treatment and rapidly worsens, resulting in severe bulbar muscle involvement and myasthenic crisis and significantly elevated serum creatine kinase levels. MG and myositis, which may occur concomitantly as irAEs are often indistinguishable. Myocarditis is occasionally observed in patients with irAE-MG and can cause severe heart failure and lethal arrhythmias, with a fatal outcome. Kv1.4 antibodies serve as biomarkers of severe irAE-MG and myocarditis. Immunotherapy with corticosteroids is effective for management of irAE-MG and should be initiated promptly. Collaboration between consulting neurologists is necessary for safe management of cancer immunotherapy.