Systemic lupus erythematosus is considered a prototype of human autoimmune disease based on the appearance of multiple autoantibodies, some of which can have a direct pathogenic effect on tissues. Most therapeutic modalities aim to check the enhanced humoral responses by targeting T and B cells with conventional or biologic drugs. However, in some cases, the clinical response is limited and frequently takes a high toll of toxicity in patients. The last 2 decades have brought up novel discoveries showing profound disturbances of innate immune cell function in systemic lupus erythematosus, including dysregulated NETosis, increased apoptosis, type 1 interferon, and granulopoiesis signatures that are grounded in basic cell biology abnormalities, including response to excessive oxidative stress, mitochondrial dysfunction, and upregulation of the cGAS-STING pathway. Whether the prominent autoimmunity component of lupus patients is sufficient to drive this chronic disease or follows a breakdown of innate immune homeostasis in response to the environmental factors triggering disease is the subject of this revision.

Ocular myasthenia gravis (OMG) is a localized form of myasthenia gravis (MG) that primarily affects the extraocular muscles, causing symptoms such as ptosis and diplopia. Without treatment, patients with OMG can progress to generalized MG (gMG), which involves systemic muscle weakness and can lead to severe complications. Immunosuppressive therapy aims to modulate the autoimmune response that underlies MG by reducing the production of pathogenic autoantibodies against the acetylcholine receptors (AChRs) or related neuromuscular junction components. This systematic review and meta-analysis evaluated the effectiveness of immunosuppressive therapy in preventing progression from OMG to gMG. A comprehensive literature search was conducted across PubMed, Web of Science, and Embase databases for studies published through January 2025. Ten retrospective observational studies met inclusion criteria, comprising 1,458 participants, with 761 receiving immunosuppression therapy. The meta-analysis revealed that immunosuppressive therapy significantly reduced the risk of generalization compared to control groups (OR: 0.23, 95%CI: 0.15-0.38, I2: 34%), representing a 77% decrease in progression rate. Sensitivity analyses demonstrated robust findings, with consistent ORs ranging from 0.21 to 0.27 after sequential removal of individual studies. The funnel plot showed no significant publication bias. However, the review was limited by the retrospective nature of included studies, moderate heterogeneity, and predominant focus on Western populations. These findings support the use of immunosuppressive therapy in preventing OMG progression, though further research through multicenter randomized controlled trials is needed to establish optimal treatment protocols, particularly in Asian populations. Future studies should also investigate biomarkers for treatment response and compare effectiveness between different immunosuppressive regimens.

The last 10 years has brought transformative developments in the effective treatment of myasthenia gravis (MG). Beginning with the randomized trial of thymectomy in myasthenia gravis that demonstrated efficacy of thymectomy in nonthymomatous MG, several new treatment approaches have completed successful clinical trials and regulatory launch. These modalities, including B cell depletion, complement inhibition, and blockade of the neonatal Fc receptor, are now in use, offering prospects of sustained remission and neuromuscular protection in what is a long-term disease. In this review, we update our clinico-immunological review of 2016 with these important advances, examine their role in treatment algorithms, and focus attention on key issues of biomarkers for prognostication and the growing cohort of older patients, both those with long-term disease, and late-onset MG ('LOMG'). We close by expressing our four hopes for the next 5-10 years: improvements in laboratory medicine to facilitate rapid diagnosis, effective strategies for neuromuscular protection, more research into and better understanding of pathophysiology and treatment response in older individuals, and the potentially transformative role of therapies aimed at delivering a durable response such as chimeric antigen receptor (CAR) T cells. Our postscript summarizes some emerging themes in the field of serological and online biomarkers, which may develop greater stature in the next epoch.

Myasthenia gravis (MG) is an acquired autoimmune disease characterized by impaired transmission at the neuromuscular junction, primarily manifesting as fluctuating muscle weakness, fatigability, and partial paralysis. Due to its long disease course, treatment resistance, and frequent relapses, it places a significant burden on patients and their families. In recent years, advances in molecular biology have provided growing evidence that mitochondrial dysfunction impairs muscle function and affects immune cell proliferation and differentiation in patients. Mitochondria, as the cell's energy source, play a critical role in various pathological processes in MG, including oxidative stress, dynamic abnormalities, mitophagy, and mitochondrial metabolism. The role of mitochondrial dysfunction in the pathogenesis of MG has garnered increasing attention. This manuscript primarily explores mitochondrial function and abnormal morphological changes in MG, as well as mitochondrial quality control, metabolic reprogramming, and their potential mechanisms in the pathological changes of the disease. It also reviews the current status of drug therapies aimed at improving mitochondrial function. The goal is to provide novel perspectives and strategies for future mitochondrial-targeted therapies in MG.

Myasthenia gravis (MG) is an acquired autoimmune disease that is mediated by humoral immunity, supplemented by cellular immunity, along with participation of the complement system. The pathogenesis of MG is complex; although autoimmune dysfunction is clearly implicated, the specific mechanism remains unclear. Long non-coding RNAs (lncRNAs) are a class of non-coding RNA molecules with lengths greater than 200 nucleotides, with increasing evidence of their rich biological functions and high-level structure conservation. LncRNAs can directly interact with proteins and microRNAs to regulate the expression of target genes at the transcription and post-transcription levels. In recent years, emerging studies have suggested that lncRNAs play roles in the differentiation of immune cells, secretion of immune factors, and complement production in the human body. This suggests the involvement of lncRNAs in the occurrence and progression of MG through various mechanisms. In addition, the differentially expressed lncRNAs in peripheral biofluid may be used as a biomarker to diagnose MG and evaluate its prognosis. Moreover, with the development of lncRNA expression regulation technology, it is possible to regulate the differentiation of immune cells and influence the immune response by regulating the expression of lncRNAs, which will provide a potential therapeutic option for MG. Here, we review the research progress on the role of lncRNAs in different pathophysiological events contributing to MG, focusing on specific lncRNAs that may largely contribute to the pathophysiology of MG, which could be used as potential diagnostic biomarkers and therapeutic targets.

Myasthenia gravis (MG) is a typical autoimmune disease of the nervous system. It is characterized by skeletal muscle weakness and fatigue due to impaired neuromuscular junction transmission mediated by IgG autoantibodies. Muscle-specific receptor tyrosine kinase-associated MG (MuSK-MG), a rare and severe subtype of MG, is distinguished by the presence of anti-MuSK antibodies; it responds poorly to traditional therapies. Recent research on MuSK-MG treatment has focused on specific targeted therapies. Since B cells play a critical pathogenic role in producing autoantibodies and inflammatory mediators, they are often considered the preferred target for treating MuSK-MG. Currently, various B cell-targeted drugs have been developed to treat MuSK-MG; they have shown good therapeutic effects. This review explores the evolving landscape of B cell-targeted therapies in MuSK-MG, focusing on their mechanisms, efficacy, and safety, and the current limitations associated with their use. We discuss current B cell-targeted therapies aimed at depleting or modulating B cells via both direct and indirect approaches. Furthermore, we focus on novel and promising strategies such as Chimeric Autoantibody Receptor T cell therapy, which explicitly targets MuSK-specific B cells without compromising general humoral immunity. Finally, this review provides an outlook on the potential benefits and limitations of B cell-targeted therapy in developing new therapies for MuSK-MG. We conclude by discussing future research efforts needed to optimize these therapies, expand treatment options, and improve long-term outcomes in MuSK-MG management.

Acquired myasthenia gravis (MG) is an autoimmune disease targeting the specific proteins in the postsynaptic muscle membrane. 50% of ocular and 80% of generalized MG have acetylcholine receptor antibodies (AChR Abs). 1-10% of MG patients have antibodies against muscle-specific kinase (MuSK), and 2-50 % of seronegative MG cases have antibodies against lipoprotein-receptor-related protein4 antibodies (LRP4 Abs). Serological testing is crucial for diagnosing and determining the appropriate therapeutic approach for MG patients. The radioimmunoprecipitation assay (RIPA) method is a historical standard test for detecting the AChR Abs and MuSK Abs. While it has nearly 100% specificity in the AChR Abs detection, its sensitivity is between 50--92%. The sensitivity and specificity of RIPA for detecting MuSK Abs is much lower. The fixed and live Cell-Based assays (f-CBA and L- CBA) have higher sensitivity than RIPA. With advancements in the serological diagnosis and management of MG, we now recommend a complete reflex testing algorithm on the first pretreatment sample of a suspected MG patient, starting with the binding and blocking assays for AChR Abs by RIPA and/ or f-CBA. If AChR Ab is negative, then reflex to MuSK Abs by RIPA and/ or CBAs. If AChR and MuSK Abs are negative, then use clustered L-CBA by request.

Autoimmune autonomic ganglionopathy (AAG) is a rare disease wherein autoantibodies target the ganglionic acetylcholine receptor (gAChR). Current diagnosis in the United States depends upon clinical symptoms and positive autoantibody detection using a radioimmunoprecipitation assay (RIA). Here we offer a proof-of-principle study on an alternative method, fluorescence-detection size-exclusion-chromatography (FSEC). We show FSEC can detect autoantibodies against gAChR from patient sera but not healthy controls or samples from other autoimmune diseases. We compare FSEC to RIA and find good correlation. We discuss potential advantages of using FSEC as an alternative or as a first-step diagnostic prior to pursuing existing methodologies.

The 275th ENMC workshop on the diagnosis and management of seronegative myasthenia gravis (SNMG) was held on February 9-11, 2024. The participants included experts in the field of adult and pediatric MG together with patient representatives. This workshop aimed to redefine SNMG in view of recent diagnostic and therapeutic updates and to identify patient unmet needs. The workshop has highlighted considerable challenges in the SNMG diagnostic work-up. To date, SNMG confirmation is often controversial, given the absence of specific diagnostic tests; no recommendations from international panels of experts are available in literature; myopathies, congenital myasthenic syndromes and functional disorders are the commonest misdiagnoses. Improving the disease diagnosis is crucial to avoid long delays in receiving appropriate treatment. To this purpose, a comprehensive diagnostic algorithm achieved consensus. Moreover, a remarkable variability in SNMG response to therapy and long-term prognosis has also been highlighted.

Fatigue is a common complaint among patients with myasthenia gravis (MG). In this study, we investigated the alterations in muscle morphology in patients with MG experiencing fatigue using quantitative electromyography (QEMG), and explored the relationship between electrophysiological findings and the severity of both fatigue and disease.

We performed QEMG of the biceps brachii muscle using the peak ratio method and multi-motor unit potential (MUP) analysis across three groups: 18 MG patients with fatigue, 34 MG patients without fatigue, and 33 healthy subjects. Stimulated single-fiber EMG was performed on the frontalis muscle. The severity of perceived fatigue and disease was subsequently assessed using the quantitative myasthenia gravis (QMG) score, the MG-activities of daily living (MG-ADL) profile, self-reported fatigue questionnaires, and handgrip strength measurements.

The QEMG study revealed a reduced mean MUP duration and size index (SI), in addition to an increased peak ratio in patients with MG (p < 0.05), which tended to be more pronounced in those experiencing fatigue. Compared to healthy subjects, MG patients with fatigue displayed a myopathic pattern characterised by a high peak ratio, short duration, and small-amplitude MUPs, without any increase in the number of phases or small time intervals. The mean peak ratio was positively correlated with the QMG, MG-ADL, and Fatigue Impact Scale total and physical subscores (p < 0.05). Further, MG patients with fatigue exhibited reduced maximum grip strength, which was positively correlated with the mean MUP duration, amplitude, SI, and thickness, and negatively correlated with the mean peak ratio (p < 0.05). No significant differences were observed in the jitter or block measurements (p > 0.05).

The present study investigated electrophysiological findings that were not considered or theorised in prior studies on patients with MG experiencing fatigue. The results of this study suggest that myopathic changes may be a critical pathophysiological component underlying the fatigue associated with MG.

Myasthenia gravis (MG) is a multifaceted autoimmune disorder affecting the postsynaptic neuromuscular junction. In this study, we examined CD4+ and CD8+ T lymphocyte levels and ratios within peripheral blood mononuclear cells (PBMCs) in MG patients. Additionally, we assessed lymphocytes for the expression of CD71, which functions as a transferrin receptor mediating the uptake of iron into the cells. Building on recent discussions regarding CD20 depletion treatments in MG, we also scrutinized lymphocytes for CD20 expression. Comparative analyses were conducted among healthy controls, newly diagnosed MG patients, those undergoing pyridostigmine treatment alone, and MG patients receiving combination therapies. In the patients, the ratio of CD3+CD4+ T lymphocytes to CD3+ T lymphocytes was found to be decreased compared to the healthy controls, while the ratio of CD3+CD8+ cells to CD3+CD4+ cells increased. An increase in the percentage of CD71-expressing lymphocytes was observed in MG patients compared to the healthy control group, while CD20+ lymphocytes exhibited no statistical changes. Moreover, heightened serum lipid peroxidation levels were found in MG patients. These results suggest a possible relationship between iron metabolism, levels of CD71-expressing cells, and lipid peroxidation in MG. Conversely, pyridostigmine treatment reduced the levels of CD71-expressing cells and lipid peroxidation, suggesting potential immunomodulatory and antioxidant impacts of pyridostigmine in MG, either directly or indirectly.

Myasthenia gravis (MG) is chronic autoimmune disorder characterized primarily by muscle weakness and fatigue, due to autoantibodies targeting acetylcholine receptor at neuromuscular junction. Herein, it was aimed to evaluate nonmotor symptoms in MG patients and compare them with disease duration, severity, and clinical features.

This prospective study was conducted with two groups: 35 MG patients and 35 healthy volunteers. The patient group comprised 17 females and 18 males with a mean age of 52.9 ± 13.6 years. The control group comprised 23 females and 12 males with a mean age of 46.9 ± 12.2 years. The Myasthenia Gravis Foundation of America clinical classification and Myasthenia Gravis Composite and Turkish version of the Myasthenia Gravis Quality of Life 15 scales were applied to the patient group. To assess nonmotor functions, questionnaires evaluating the symptoms of headache, pain, depression, anxiety, sleep, physical activity, cognition, smell, and taste were applied to both the patient and control groups.

The results revealed prevalent and diverse nonmotor symptoms in the MG group. The Montreal Cognitive Assessment (MoCA) score and degree of olfactory function in cinnamon was statistically significantly (p < 0.05) lower in the patient group than in the control group. The degree of impairment on the MoCA, headache rate, Beck depression score, depression rate, Beck anxiety score, anxiety rate, Pittsburgh Sleep Quality Index (PSQI) score, and poor sleep quality rate were significantly higher (p < 0.05) in the patient group than in the control group.

In conclusion, this study emphasizes the importance of recognizing and managing nonmotor symptoms in MG patients, advocating for a multidisciplinary approach to care that addresses both motor and nonmotor manifestations. By expanding our understanding of the systemic impact of MG and exploring new treatment modalities, we can improve the lives of those living with this complex autoimmune disorder. Further research is needed to elucidate the pathogenic mechanisms underlying these nonmotor manifestations, which will be pivotal in developing more targeted and effective therapeutic strategies.

Olfactory loss accompanies at least 139 neurological, somatic, and congenital/hereditary conditions. This observation leads to the question of whether these associations are correlations or whether they are ever causal. Temporal precedence and prospective predictive power suggest that olfactory loss is causally implicated in many medical conditions. The causal relationship between olfaction with memory dysfunction deserves particular attention because this sensory system has the only direct projection to memory centers. Mechanisms that may underlie the connections between medical conditions and olfactory loss include inflammation as well as neuroanatomical and environmental factors, and all 139 of the medical conditions listed here are also associated with inflammation. Olfactory enrichment shows efficacy for both prevention and treatment, potentially mediated by decreasing inflammation.

Myasthenia gravis is an autoimmune disease with high prevalence of thymus disorders, in which, thymectomy is considered one of the therapeutic approaches in improving the patients' clinical outcomes. Today, thoracoscopic thymectomy has received significant attention than the classic transsternal approach due to fewer complication. Therefore, this study was designed with the aim of investigating the therapeutic outcomes of thymectomy in patients with myasthenia gravis in the Afzalipour Hospital of Kerman between 2011 and 2021.

The current study is a descriptive analytical study on patients with myasthenia gravis who underwent surgical thymectomy within 2011-2021. Demographic and clinical characteristics of patients from the time of operation to three years of follow-up were extracted and recorded from clinical records or by phone calls. Data were analyzed using SPSS software.

The data of 70 patients who underwent surgical thymectomy were analyzed. Thymectomy caused a significant reduction in the severity of the disease according to the Osserman classification (P = 0.001). It also significantly reduced the use of corticosteroids (P = 0.001) and IVIG (P = 0.015) compared to the time before the surgery. Sixty-two patients (88.57%) needed to take less medicine than before surgery. Left VATS was associated with less post-operative severity of the disease (P = 0.023). There were only two deaths during the follow-up period.

Overall, the findings of the present study demonstrated that thoracoscopic thymectomy is a useful surgical approach that leads to faster recovery, reducing the severity of the disease, need for medication, and complications in patients with myasthenia gravis, In comparison with the transsternal approach.

Cholinesterase (ChE) inhibitors are crucial therapeutic agents for the symptomatic treatment of certain chronic neurodegenerative diseases linked to functional disorders of the cholinergic system. Significant research efforts have been made to develop novel derivatives of classical ChE inhibitors and ChE inhibitors with novel scaffolds. Over the past decade, ruthenium complexes have emerged as promising novel therapeutic alternatives for the treatment of neurodegenerative diseases. Our research group has investigated a number of newly synthesized organoruthenium(II) complexes for their inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Three complexes (C1a, C1-C, and C1) inhibit ChE in a pharmacologically relevant range. C1a reversibly inhibits AChE and BChE without undesirable peripheral effects, making it a promising candidate for the treatment of Alzheimer's disease. C1-Cl complex reversibly and competitively inhibits ChEs, particularly AChE. It inhibits nerve-evoked skeletal muscle twitch and tetanic contraction in a concentration-dependent manner with no effect on directly elicited twitch and tetanic contraction and is promising for further preclinical studies as a competitive neuromuscular blocking agent. C1 is a selective, competitive, and reversible inhibitor of BChE that inhibits horse serum BChE (hsBChE) without significant effect on the peripheral neuromuscular system and is a highly species-specific inhibitor of hsBChE that could serve as a species-specific drug target. This research contributes to the expanding knowledge of ChE inhibitors based on ruthenium complexes and highlights their potential as promising therapeutic candidates for chronic neurodegenerative diseases.

Myasthenia gravis (MG) is a neuromuscular disease of autoimmune etiology and chronic evolution. In addition to the muscle weakness and fatigue that characterize MG, in some studies patients show an inferior performance in cognitive tasks and difficulties in recognizing basic emotions from facial expressions. However, it remains unclear if these difficulties are due to anxious-depressive symptoms that these patients present or related to cognitive abilities, such as facial recognition. This study had a descriptive cross-sectional design with a sample of 92 participants, 52 patients with MG and 40 healthy controls. The data collection protocol included measures to assess recognition of facial expressions (BRFT), facial emotional expression (FEEL), and levels of anxiety and depression (HADS). The MG group had worse performance than the control group in recognizing "fear" (p = 0.001; r = 0.344), "happiness" (p = 0.000; r = 0.580), "disgust" (p = 0.000; r = 0.399), "surprise" (p = 0.000; r = 0.602), and "anger" (p = 0.007; r = 0.284). Likewise, the MG group also underperformed in facial recognition (p = 0.001; r = 0.338). These difficulties were not related to their levels of anxiety and depression. Alterations were observed both in the recognition of facial emotions and in facial recognition, without being mediated by emotional variables. These difficulties can influence the interpersonal interaction of patients with MG.

Myasthenia gravis (MG) is one of the most well characterised autoimmune disorders affecting the neuromuscular junction with autoantibodies targeting the acetylcholine receptor (AChR) complex. The vast majority of patients present with ocular symptoms including double vision and ptosis, but may progress on to develop generalised fatiguable muscle weakness. Severe involvement of the bulbar muscles can lead to dysphagia, dysarthria and breathing difficulties which can progress to myasthenic crisis needing ventilatory support. Given the predominant ocular onset of the disease, it is important that ophthalmologists are aware of the differential diagnosis, investigations and management including evolving therapies. When the disease remains localised to the extraocular muscles (ocular MG) IgG1 and IgG3 antibodies against the AChR (including clustered AChR) are present in nearly 50% of patients. In generalised MG this is seen in nearly 90% patients. Other antibodies include those against muscle specific tyrosine kinase (MuSK) and lipoprotein receptor related protein 4 (LRP4). Even though decremental response on repetitive nerve stimulation is the most well recognised neurophysiological abnormality, single fibre electromyogram (SFEMG) in experienced hands is the most sensitive test which helps in the diagnosis. Initial treatment should be using cholinesterase inhibitors and then proceeding to immunosuppression using corticosteroids and steroid sparing drugs. Patients requiring bulbar muscle support may need rescue therapies including plasma exchange and intravenous immunoglobulin (IVIg). Newer therapeutic targets include those against the B lymphocytes, complement system, neonatal Fc receptors (FcRn) and various other elements of the immune system.

Serological testing for anti-acetylcholine receptor (AChR) autoantibodies is not only crucial for the diagnosing, disease monitoring, and treatment management of patients with myasthenia gravis (MG) but also for preclinical studies utilizing MG disease models. However, there are no specific guidelines on which methods to use in clinical diagnostic or research laboratories to detect or quantify any MG-specific autoantibodies. Conventional autoantibody assays, particularly those for anti-AChR antibodies, are varied and mostly laboratory-specific. Here, we report our new nonradioactive immunoprecipitation-immunoblotting method for assessing autoantibodies (anti-AChR antibodies) in a mouse model of MG. This simple, efficient, reproducible, and cost-effective assay appears superior to the enzyme-linked immunosorbent assay but comparable to the radioimmunoprecipitation or cell-based assay in specificity and sensitivity. Thus, the newly developed assay can serve as a valuable alternative to classical assays and is suitable for routine testing of AChR-specific autoantibodies in preclinical studies. The further optimization of our assay may facilitate its application in the diagnosis and therapeutic management of patients with MG.

Myasthenia gravis (MG) is the most frequent transmission disease in the neuromuscular junction. Juvenile myasthenia gravis (JMG) is an autoimmune antibody-mediated disease of postsynaptic endplate defined as MG presentation in patients before the age of 18 years old. While many clinical features of JMG are identical to the adults, there are some significant differences between them regarding presentation, clinical course, antibody level, and thymus histopathology. In JMG, ocular symptoms are more frequent, the clinical course is comparably benign, and the outcome is better than adult MG. Antibodies attack the muscle endplate proteins in the postsynaptic membrane and interfere with transmission. These antibodies in most patients are against the acetylcholine receptors, but they may also be directed toward muscle-specific kinase, lipoprotein-related protein 4, and agrin. Findings show racial influences and genetic effects on the occurrence of JMG. The essential clinical symptom is fatigable weakness of muscles that can be in the form of isolated ocular type or more disseminated weakness. The diagnosis of JMG is essentially clinical, with fluctuating patterns of weakness and easy fatigability, but a series of diagnostic evaluations can confirm the diagnosis. Precise diagnostic evaluation and distinction from congenital myasthenic syndromes is critical. The treatment plan is conducted according to the clinical course (ocular or generalized), antibody type, and disease severity. The mainstay of treatment includes symptomatic therapy, long-lasting immunosuppressive treatment and treatment of myasthenic crisis. Novel medications are introduced and conducted to the specific pathophysiologic mechanisms of the disease, and they are used primarily in the refractory MG.

Myasthenia Gravis (MG) is a chronic disabling autoimmune disease caused by autoantibodies to the neuromuscular junction (NMJ), characterized clinically by fluctuating weakness and early fatigability of ocular, skeletal and bulbar muscles. Despite being commonly considered a prototypic autoimmune disorder, MG is a complex and heterogeneous condition, presenting with variable clinical phenotypes, likely due to distinct pathophysiological settings related with different immunoreactivities, symptoms' distribution, disease severity, age at onset, thymic histopathology and response to therapies. Current treatment of MG based on international consensus guidelines allows to effectively control symptoms, but most patients do not reach complete stable remission and require life-long immunosuppressive (IS) therapies. Moreover, a proportion of them is refractory to conventional IS treatment, highlighting the need for more specific and tailored strategies. Precision medicine is a new frontier of medicine that promises to greatly increase therapeutic success in several diseases, including autoimmune conditions. In MG, B cell activation, antibody recycling and NMJ damage by the complement system are crucial mechanisms, and their targeting by innovative biological drugs has been proven to be effective and safe in clinical trials. The switch from conventional IS to novel precision medicine approaches based on these drugs could prospectively and significantly improve MG care. In this review, we provide an overview of key immunopathogenetic processes underlying MG, and discuss on emerging biological drugs targeting them. We also discuss on future direction of research to address the need for patients' stratification in endotypes according with genetic and molecular biomarkers for successful clinical decision making within precision medicine workflow.

Generalized myasthenia gravis (gMG) continues to present significant challenges for clinical management due to an unpredictable disease course, frequent disease fluctuations, and varying response to therapy. The recent availability of new pharmacologic therapies presents a valuable opportunity to reevaluate how this disease is classified, assessed, and managed and identify new ways to improve the clinical care of patients with gMG.

Narrative review was made of publications identified via searches of PubMed and selected congresses (January 2000-September 2022).

New consensus definitions are required to ensure consistency, to better characterize patients, and to identify patients who will benefit from specific drugs and earlier use of these agents. There is a need for more frequent, standardized patient assessment to identify the cause of motor function deficits, provide a clearer picture of the disease burden and its impact on daily living and quality of life (QoL), and better support treatment decision-making. Novel approaches that target different components of the immune system will play a role in more precise treatment of patients with gMG, alongside the development of new algorithms to guide individualized patient management.

gMG has a physical, mental, and social impact, resulting in a considerable burden of disease and substantially decreased QoL, despite standard treatments. The availability of novel, targeted treatments that influence key pathological mediators of gMG, together with new biomarkers, offers the potential to optimize patient management and ultimately enables a greater number of patients to achieve minimal manifestation status and a reduced burden of disease.

Myasthenia gravis (MG) is one of the most common autoimmune diseases and can occur at any age. The study aimed to evaluate the influence of loneliness and anxiety levels on MG-specific quality of life in patients with myasthenia gravis during the COVID-19.

This was a cross sectional study and the population consisted of patients with MG throughout Turkey between August 1 and October 31, 2021. The study was completed with 149 patients who met the inclusion criteria and agreed to participate in the research.

The mean MG-specific quality of life score was 44.15 ± 13.77, the mean UCLA loneliness scale was 56.13 ± 11.55, and the mean Beck Anxiety Inventory score was 24.63 ± 13.78. There was a moderately positive linear relationship between the participants' MG-specific quality of life (r = 0.589; p < 0.001) and the Beck Anxiety Inventory, and there was a weak negative linear relationship with the UCLA loneliness scale (r = 0.323; p < 0.001). The variables affecting the MG-specific quality of life were the following: anxiety, loneliness, employment status, income level, symptom levels, and having another chronic disease; a multiple regression model was created with these variables, and it was observed that anxiety and loneliness affected participants' MG-specific quality of life. The variables in the model explained 52.9% of the MG-specific quality of life, and the model was statistically significant (p < 0.001).

The study determined that the participants had intense loneliness, moderate anxiety, and a moderate MG-specific quality of life. The participants' MG-specific quality of life has decreased as their anxiety has increased, and the participants' MG-specific quality of life has increased as their loneliness has increased.

Muscle-specific kinase (MuSK)- myasthenia gravis (MG) is caused by pathogenic autoantibodies against MuSK that correlate with disease severity and are predominantly of the IgG4 subclass. The first-line treatment for MuSK-MG is general immunosuppression with corticosteroids, but the effect of treatment on IgG4 and MuSK IgG4 levels has not been studied.

We analyzed the clinical data and sera from 52 MuSK-MG patients (45 female, 7 male, median age 49 (range 17-79) years) from Italy, the Netherlands, Greece and Belgium, and 43 AChR-MG patients (22 female, 21 male, median age 63 (range 2-82) years) from Italy, receiving different types of immunosuppression, and sera from 46 age- and sex-matched non-disease controls (with no diagnosed diseases, 38 female, 8 male, median age 51.5 (range 20-68) years) from the Netherlands. We analyzed the disease severity (assessed by MGFA or QMG score), and measured concentrations of MuSK IgG4, MuSK IgG, total IgG4 and total IgG in the sera by ELISA, RIA and nephelometry.

We observed that MuSK-MG patients showed a robust clinical improvement and reduction of MuSK IgG after therapy, and that MuSK IgG4 concentrations, but not total IgG4 concentrations, correlated with clinical severity. MuSK IgG and MuSK IgG4 concentrations were reduced after immunosuppression in 4/5 individuals with before-after data, but data from non-linked patient samples showed no difference. Total serum IgG4 levels were within the normal range, with IgG4 levels above threshold (1.35g/L) in 1/52 MuSK-MG, 2/43 AChR-MG patients and 1/45 non-disease controls. MuSK-MG patients improved within the first four years after disease onset, but no further clinical improvement or reduction of MuSK IgG4 were observed four years later, and only 14/52 (26.92%) patients in total, of which 13 (93.3%) received general immunosuppression, reached clinical remission.

We conclude that MuSK-MG patients improve clinically with general immunosuppression but may require further treatment to reach remission. Longitudinal testing of individual patients may be clinically more useful than single measurements of MuSK IgG4. No significant differences in the serum IgG4 concentrations and IgG4/IgG ratio between AChR- and MuSK-MG patients were found during follow-up. Further studies with larger patient and control cohorts are necessary to validate the findings.

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.

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.

Narrative literature review.

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.

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.

Myasthenia gravis (MG) is an autoimmune disease in which autoantibodies target structures within the neuromuscular junction, affecting neuromuscular transmission. Muscle-specific tyrosine kinase receptor-associated MG (MuSK-MG) is a rare, often more severe, subtype of the disease with different pathogenesis and specific clinical features. It is characterized by a more severe clinical course, more frequent complications, and often inadequate response to treatment. Here, we review the current state of knowledge about potential pathomechanisms of the MuSK-MG and their therapeutic implications as well as ongoing research in this field, with reference to key points of immune-mediated processes involved in the background of myasthenia gravis.

The neuromuscular junction (NMJ) is a crucial structure that connects the cholinergic motor neurons to the muscle fibers and allows for muscle contraction and movement. Despite the interruption of the supraspinal pathways that occurs in spinal cord injury (SCI), the NMJ, innervated by motor neurons below the injury site, has been found to remain intact. This highlights the importance of studying the NMJ in rodent models of various nervous system disorders, such as amyotrophic lateral sclerosis (ALS), Charcot-Marie-Tooth disease (CMT), spinal muscular atrophy (SMA), and spinal and bulbar muscular atrophy (SBMA). The NMJ is also involved in myasthenic disorders, such as myasthenia gravis (MG), and is vulnerable to neurotoxin damage. Thus, it is important to analyze the integrity of the NMJ in rodent models during the early stages of the disease, as this may allow for a better understanding of the condition and potential treatment options. The spinal cord also plays a crucial role in the functioning of the NMJ, as the junction relays information from the spinal cord to the muscle fibers, and the integrity of the NMJ could be disrupted by SCI. Therefore, it is vital to study SCI and muscle function when studying NMJ disorders. This review discusses the formation and function of the NMJ after SCI and potential interventions that may reverse or improve NMJ dysfunction, such as exercise, nutrition, and trophic factors.

Myasthenia gravis (MG) is a T cell-dependent, B cell-mediated, and complement-dependent autoimmune disease. Lymphocyte activation gene-3 (LAG-3; CD223) is an immune checkpoint protein that plays an important role in maintaining autoimmune tolerance and homeostasis. To investigate the cytokine-regulated expression pattern of LAG-3, CD4+T cells were sorted from the peripheral blood of healthy volunteers by density gradient centrifugation and stimulated with various cytokines in vitro. The expression of membrane LAG-3 (mLAG-3), membrane a disintegrin and metallopeptidase domain10 (mADAM10) and membrane ADAM17 (mADAM17) on CD4+T cells was detected by flow cytometry; the concentration of soluble LAG-3 (sLAG-3) was detected by ELISA; and the relative expression of genes at the transcriptional level was detected by fluorescence quantitative RT-PCR (qRT-PCR). sLAG-3 levels were significantly increased in the peripheral plasma of AChR Ab-positive patients with MG compared to healthy volunteers, while the percentage of mLAG-3 expression on CD4+T lymphocytes in the peripheral blood of patients with MG was significantly reduced. IL-18 inhibited mLAG-3 levels on CD4+T cells in a concentration-dependent manner. Additionally, the concentration of sLAG-3 in the supernatant increased. After PHA and IL-18 stimulation, ADAM10 and ADAM17 also increased compared to those in the PHA-active group. Moreover, there were significant differences in the expression of mADAM10 and mADAM17 in CD4+T lymphocytes between patients with MG and healthy volunteers. These results suggest that IL-18 may regulate the expression pattern of mLAG-3 in CD4+T cells and sLAG-3 via ADAM10- and ADAM17-mediated pathways, thus affecting the immune effects of CD4+T cells. This study provides a preliminary exploration of the upstream regulatory molecules of the LAG-3 and IL-18/LAG-3 signalling pathways for potential targeted therapy of autoimmune diseases in the future.

The mechanism of action of low-density lipoprotein receptor related protein 4 (LRP4) is mediated largely via the Agrin-LRP4-MuSK signalling pathway in the nervous system. LRP4 contributes to the development of synapses in the peripheral nervous system (PNS). It interacts with signalling molecules such as the amyloid beta-protein precursor (APP) and the wingless type protein (Wnt). Its mechanisms of action are complex and mediated via interaction between the pre-synaptic motor neuron and post-synaptic muscle cell in the PNS, which enhances the development of the neuromuscular junction (NMJ). LRP4 may function differently in the central nervous system (CNS) than in the PNS, where it regulates ATP and glutamate release via astrocytes. It mayaffect the growth and development of the CNS by controlling the energy metabolism. LRP4 interacts with Agrin to maintain dendrite growth and density in the CNS. The goal of this article is to review the current studies involving relevant LRP4 signaling pathways in the nervous system. The review also discusses the clinical and etiological roles of LRP4 in neurological illnesses, such as myasthenia gravis, Alzheimer's disease and epilepsy. In this review, we provide a theoretical foundation for the pathogenesis and therapeutic application of LRP4 in neurologic diseases.

It has become increasingly clear that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect most organs in the human body, including the neurologic and ophthalmic systems. Vaccination campaigns have been developed at rapid pace around the world to protect the population from the fast-mutating virus. This review seeks to summarise current knowledge of the neuro-ophthalmic manifestations of both COVID-19 infection and vaccination.

Electronic searches for published literature were conducted using EMBASE and MEDLINE on the 30th of July 2023. The search strategy comprised of controlled vocabulary and free-text synonyms for the following terms in various combinations: "coronavirus, COVID-19, SARS-CoV-2, 2019-nCoV, vaccination, vaccine, immunisation and neuro-ophthalmology". No time range limits were set for the literature search. Published English abstracts for articles written in a different language were screened if available.

A total of 54 case reports and case series were selected for use in the final report. 34 articles documenting neuro-ophthalmic manifestations following COVID-19 infection and 20 articles with neuro-ophthalmic complications following COVID-19 vaccination were included, comprising of 79 patients in total. The most commonly occurring condition was optic neuritis, with 25 cases following COVID-19 infection and 27 cases following vaccination against COVID-19.

The various COVID-19 vaccines that are currently available are part of the global effort to protect the most vulnerable of the human population. The incidence of neuro-ophthalmic consequences following infection with COVID-19 is hundred-folds higher and associated with more harrowing systemic effects than vaccination against the virus.

  Myasthenia gravis (MG) is an autoimmune disease usually caused by antibodies against the acetylcholine receptor (AChR-Abs), muscle-specific tyrosine kinase (MuSK-Abs), or low-density lipoprotein receptor-related protein 4 (LRP4-Abs). However, there are MG patients who do not have these antibodies and are thus said to have triple-seronegative (triple-SN) MG.

 This study aims to describe the frequency and clinical and epidemiological characteristics of patients with triple-SN MG.

 This was a retrospective cross-sectional study carried out through the analysis of medical records. Descriptive and analytical statistical analysis was performed comparing subgroups of myasthenic patients, classified according to serological profile.

 The sample population consisted of 93 MG patients: 85 were positive for antibodies, 80 (86%) with AChR-Abs, 5 (5.4%) with MuSK-Abs, and no MG patients with LRP4-Abs. Eight patients (8.6%) had triple-SN MG; they had a median age at disease onset of 30 years (21-45). Their most common initial symptoms were ptosis, diplopia, and generalized weakness. Most patients presented with mild symptoms at their last visit, reflecting a median MG composite scale score of 4 (0-6), and 75% of patients had an adequate response to treatment.

 Our study showed a low frequency of triple-SN MG in Brazilian MG patients. Triple-SN MG was predominant in females, who presented with ptosis, diplopia, and generalized weakness, and most patients had an adequate response to immunosuppressive treatment. There was no significant difference between triple-SN MG and the other subgroups.

Dysrhythmia is a term referring to the occurrence of spontaneous and repetitive changes in potentials with parameters deviating from those considered normal. The term refers to heart anomalies but has a broader meaning. Dysrhythmias may concern the heart, neurological system, digestive system, and sensory organs. Ion currents conducted through ion channels are a universal phenomenon. The occurrence of channel abnormalities will therefore result in disorders with clinical manifestations depending on the affected tissue, but phenomena from other tissues and organs may also manifest themselves. A similar problem concerns the implementation of pharmacotherapy, the mechanism of which is related to the impact on various ion currents. Treatment in this case may cause unfavorable effects on other tissues and organs. Drugs acting through the modulation of ion currents are characterized by relatively low tissue specificity. To assess a therapy's efficacy and safety, the risk of occurrences in other tissues with similar mechanisms of action must be considered. In the present review, the focus is shifted prominently onto a comparison of abnormal electrical activity within different tissues and organs. This review includes an overview of the types of dysrhythmias and the basic techniques of clinical examination of electrophysiological disorders. It also presents a concise overview of the available pharmacotherapy in particular diseases. In addition, the authors review the relevant ion channels and their research technique based on patch clumping.

The pathophysiology of myasthenia gravis (MG) has been largely elucidated over the past half century, and treatment methods have advanced. However, the number of cases of childhood-onset MG is smaller than that of adult MG, and the treatment of childhood-onset MG has continued to be based on research in the adult field. Research on pathophysiology and treatment methods that account for the unique growth and development of children is now desired. According to an epidemiological survey conducted by the Ministry of Health, Labour and Welfare of Japan, the number of patients with MG by age of onset in Japan is high in early childhood. In recent years, MG has been reported from many countries around the world, but the pattern of the number of patients by age of onset differs between East Asia and Western Europe, confirming that the Japanese pattern is common in East Asia. Furthermore, there are racial differences in autoimmune MG and congenital myasthenic syndromes according to immunogenetic background, and their pathophysiology and relationships are gradually becoming clear. In addition, treatment options are also recognized in different regions of the world. In this review article, I will present recent findings focusing on the differences in pathophysiology.

Myasthenia gravis (MG) is a type of autoimmune disease caused by the blockage of neuromuscular junction transmission owing to the attack of autoantibodies on transmission-related proteins. Related antibodies, such as anti-AChR, anti-MuSK and anti-LRP4 antibodies, can be detected in most patients with MG. Although traditional therapies can control most symptoms, several challenges remain to be addressed, necessitating the development of more effective and safe treatment strategies for MG. With the in-depth exploration on the mechanism and immune targets of MG, effective therapies, especially therapies using biologicals, have been reported recently. Given the important roles of immune cells, cytokines and intercellular interactions in the pathological process of MG, B-cell targeted therapy, T-cell targeted therapy, proteasome inhibitors targeting plasma cell, complement inhibitors, FcRn inhibitors have been developed for the treatment of MG. Although these novel therapies exert good therapeutic effects, they may weaken the immunity and increase the risk of infection in MG patients. This review elaborates on the pathogenesis of MG and discusses the advantages and disadvantages of the strategies of traditional treatment and biologicals. In addition, this review emphasises that combined therapy may have better therapeutic effects and reducing the risk of side effects of treatments, which has great prospects for the treatment of MG. With the deepening of research on immunotherapy targets in MG, novel opportunities and challenges in the treatment of MG will be introduced.

To evaluate the association of COVID-19 infection and vaccination with neuro-ophthalmic adverse events.

In this nationwide population-based retrospective cohort study, 8,498,353 patients were classified into three groups: control, COVID-19 infection, and COVID-19 vaccination. We conducted separate analyses for the early phase (within 60 days) and late phases (61-180 days) to estimate the incidence rates and hazard ratio (HR) for each neuro-ophthalmic adverse event. The adverse events included in this analysis were optic neuritis, papilledema, ischemic optic neuropathy, third nerve palsy, fourth nerve palsy, sixth nerve palsy, facial palsy, nystagmus, ptosis, blepharospasm, anomalies of pupillary function, and Guillain-Barré syndrome/Miller Fisher syndrome (GBS/MFS).

Neuro-ophthalmic adverse events other than ptosis and GBS/MFS exhibited no significant increase after COVID-19, and their incidence was extremely low. The incidence rate of ptosis in both phases was significantly higher in patients administered COVID-19 vaccination (HR = 1.65 in the early phase and HR = 2.02 in the late phase) than in the control group. Additionally, BNT162b2 conferred a lower ptosis risk than ChAdOx1. GBS/MFS had a significantly higher incidence rate in the early phase (HR = 5.97) in patients with COVID-19 infection than in the control group.

Ptosis was associated with COVID-19 vaccination, particularly with the ChAdOx1 vaccine, while GBS/MFS was associated with COVID-19 infection. In contrast, no association was found between other neuro-ophthalmic adverse events and COVID-19 infection or vaccination. These results may provide helpful insights for diagnosing and treating the neuro-ophthalmological adverse events after COVID-19.

Myasthenia gravis (MG) is a heterogeneous autoimmune disease, which is characterized by a postsynaptic neuromuscular transmission defect, with antibodies directly targeting the acetylcholine receptor (AChR) or other structural proteins of the neuromuscular junction. The majority of MG cases are associated with thymic pathologies, including thymoma, thyroiditis, autoimmune diseases or malignant hematologic neoplasia. The present study reported a rare case of AChR-positive and late-onset ocular MG, which rapidly progressed to a generalized myasthenic syndrome as an initial presentation of a pancreatic neuroendocrine neoplasia (pNEN). Following complete surgical resection of the pNEN, the myasthenic syndrome was improved and the anti-AChR antibody titers were reduced. It has been reported that MG is a paraneoplastic syndrome in thymic neoplasms and less common in hematologic malignancies. However, currently, only few cases of MG as initial presentation of a solid tumor, and more particular of a neuroendocrine neoplasm, have been reported in the literature. In conclusion, surveillance for extrathymic solid malignancies in newly diagnosed patients with MG could promote the early diagnosis of associated tumor diseases.

There are an increasing number of reports of autoantibodies (AAbs) against host proteins such as G-protein coupled receptors (GPCRs) and the renin-angiotensin system (RAS) in COVID-19 disease. Here we have undertaken a systematic review and meta-analysis of all reports of AAbs against GPCRs and RAS in COVID-19 patients including those with long-COVID or post-COVID symptoms.

PubMed, Embase, Web of Science, and Scopus databases were searched to find papers on the role of GPCR and RAS AAbs in the presence and severity of COVID-19 or post- COVID symptoms available through March 21, 2023. Data on the prevalence of AngII or ACE, comparing AngII or ACE between COVID-19 and non-COVID-19, or comparing AngII or ACE between COVID-19 patients with different disease stages were pooled and a meta-analysed using random- or fixed-effects models were undertaken.

The search yielded a total of 1042 articles, of which 68 studies were included in this systematic review and nine in the meta-analysis. Among 18 studies that investigated GPCRs and COVID-19 severity, 18 distinct AAbs were detected. In addition, nine AAbs were found in case reports that assessed post- COVID, and 19 AAbs were found in other studies that assessed post- COVID or long- COVID symptoms. Meta-analysis revealed a significantly higher number of seropositive ACE2 AAbs in COVID-19 patients (odds ratio = 7.766 [2.056, 29.208], p = 0.002) and particularly in severe disease (odds ratio = 11.49 [1.04, 126.86], p = 0.046), whereas AngII-AAbs seropositivity was no different between COVID-19 and control subjects (odds ratio = 2.890 [0.546-15.283], p = 0.21).

GPCR and RAS AAbs may play an important role in COVID-19 severity, the development of disease progression, long-term symptoms COVID and post- COVID symptoms.

Muscle-specific kinase (MuSK) Myasthenia Gravis (MG) represents a prototypical antibody-mediated disease characterized by predominantly focal muscle weakness (neck, facial, and bulbar muscles) and fatigability. The pathogenic antibodies mostly belong to the immunoglobulin subclass (Ig)G4, a feature which attributes them their specific properties and pathogenic profile. On the other hand, acetylcholine receptor (AChR) MG, the most prevalent form of MG, is characterized by immunoglobulin (Ig)G1 and IgG3 antibodies to the AChR. IgG4 class autoantibodies are impotent to fix complement and only weakly bind Fc-receptors expressed on immune cells and exert their pathogenicity via interfering with the interaction between their targets and binding partners (e.g. between MuSK and LRP4). Cardinal differences between AChR and MuSK-MG are the thymus involvement (not prominent in MuSK-MG), the distinct HLA alleles, and core immunopathological patterns of pathology in neuromuscular junction, structure, and function. In MuSK-MG, classical treatment options are usually less effective (e.g. IVIG) with the need for prolonged and high doses of steroids difficult to be tapered to control symptoms. Exceptional clinical response to plasmapheresis and rituximab has been particularly observed in these patients. Reduction of antibody titers follows the clinical efficacy of anti-CD20 therapies, a feature implying the role of short-lived plasma cells (SLPB) in autoantibody production. Novel therapeutic monoclonal against B cells at different stages of their maturation (like plasmablasts), or against molecules involved in B cell activation, represent promising therapeutic targets. A revolution in autoantibody-mediated diseases is pharmacological interference with the neonatal Fc receptor, leading to a rapid reduction of circulating IgGs (including autoantibodies), an approach already suitable for AChR-MG and promising for MuSK-MG. New precision medicine approaches involve Chimeric autoantibody receptor T (CAAR-T) cells that are engineered to target antigen-specific B cells in MuSK-MG and represent a milestone in the development of targeted immunotherapies. This review aims to provide a detailed update on the pathomechanisms involved in MuSK-MG (cellular and humoral aberrations), fostering the understanding of the latest indications regarding the efficacy of different treatment strategies.

The coronavirus disease 2019 (COVID-19) infection commonly presents with symptoms of fever, cough, and anosmia. However, there have been case reports of unusual symptoms associated with COVID-19. We encountered one such case where a 55-year-old male who tested positive for COVID-19 was noted to have, along with cough and vomiting, a new onset of left eyelid ptosis. COVID-19 infection and ptosis association is seldom seen and very few similar studies are reported.

An altered gut microbiota is a possible contributing pathogenic factor in myasthenia gravis (MG), an autoimmune neuromuscular disease. However, the significance of the fungal microbiome is an understudied and neglected part of the intestinal microbiome in MG. We performed a sub-analysis of the MYBIOM study including faecal samples from patients with MG (n = 41), non-inflammatory neurological disorder (NIND, n = 18), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP, n = 6) and healthy volunteers (n = 12) by sequencing the internal transcribed spacer 2 (ITS2). Fungal reads were obtained in 51 out of 77 samples. No differences were found in alpha-diversity indices computed between the MG, NIND, CIDP and HV groups, indicating an unaltered fungal diversity and structure. Overall, four mould species (Penicillium aurantiogriseum, Mycosphaerella tassiana, Cladosporium ramonetellum and Alternaria betae-kenyensis) and five yeast species (Candida. albicans, Candida. sake, Candida. dubliniensis, Pichia deserticola and Kregervanrija delftensis) were identified. Besides one MG patient with abundant Ca. albicans, no prominent dysbiosis in the MG group of the mycobiome was found. Not all fungal sequences within all groups were successfully assigned, so further sub-analysis was withdrawn, limiting robust conclusions.

The aim of this study was to compare the effects of the pandemic on health-related quality of life (HRQoL), anxious-depressive symptoms, feelings of loneliness, and fear of COVID-19 between people with myasthenia gravis (MG) and healthy controls. We also wanted to know in which group the variable fear of COVID-19 interfered the most with the results. This cross-sectional study involved 60 people with MG and 60 healthy controls. Participants using an online platform completed a sociodemographic questionnaire, the Short Form-36 Health Survey (SF-36), the Hospital Anxiety and Depression Scale (HADS), the revised UCLA Loneliness Scale and the Fear of COVID19 Scale (FCV- 19S). The MG group reported worse levels in HRQoL indicators (p = 0.043- <.001), more severe anxiety-depressive symptoms (p = 0.002), and greater fear of COVID-19 (p < 0.001), but there were no differences in feelings of loneliness (p = 0.002). Furthermore, after controlling for the effect of the fear of COVID-19 variable, the differences remained for physical health indicators, but not for the most of psychosocial indicators (Social Functioning p = 0.102, η²_p = 0.023; Role Emotional p = 0.250, η²_p = 0.011; and HADS Total p = 0.161, η²_p = 0.017). The harmful effect of the COVID-19 pandemic was greater in the MG group, and the perceived fear of COVID-19 had also a greater impact among this group, which has increased its negative effect on their psychosocial health.

To describe clinical manifestations and short-term prognosis of ocular motility disorders following coronavirus disease-2019 (COVID-19) vaccination.

Ocular motility disorders were diagnosed by clinical assessment, high-resolution magnetic resonance imaging, and laboratory testing. Clinical manifestations, short-term prognosis, and rate of complete recovery were analyzed.

Sixty-three patients (37 males, 26 females) with a mean age of 61.6 ± 13.3 years (range, 22-81 years) were included in this study. Among 61 applicable patients with sufficient information regarding medical histories, 38 (62.3%) had one or more significant underlying past medical histories including vasculopathic risk factors. The interval between initial symptoms and vaccination was 8.6 ± 8.2 (range, 0-28) days. Forty-two (66.7%), 14 (22.2%), and 7 (11.1%) patients developed symptoms after the first, second, and third vaccinations, respectively. One case of internuclear ophthalmoplegia, 52 cases of cranial nerve palsy, two cases of myasthenia gravis, six cases of orbital diseases (such as myositis, thyroid eye disease, and IgG-related orbital myopathy), and two cases of comitant vertical strabismus with acute onset diplopia were found. Among 42 patients with follow-up data (duration: 62.1 ± 40.3 days), complete improvement, partial improvement, no improvement, and exacerbation were shown in 20, 15, 3, and 4 patients, respectively.

This study provided various clinical features of ocular motility disorders following COVID-19 vaccination. The majority of cases had a mild clinical course while some cases showed a progressive nature. Close follow-up and further studies are needed to elucidate the underlying mechanisms and long-term prognosis.

Muscle-specific kinase (MuSK) is the key regulator of neuromuscular junction development. MuSK acts via several distinct pathways and is responsible for pre- and postsynaptic differentiation. MuSK is unique among receptor tyrosine kinases as activation and signaling are particularly tightly regulated. Initiation of kinase activity requires Agrin, a heparan sulphate proteoglycan derived from motor neurons, the low-density lipoprotein receptor-related protein-4 (Lrp4) and the intracellular adaptor protein Dok-7. There is a great knowledge gap between MuSK activation and downstream signaling. Recent studies using omics techniques have addressed this knowledge gap, thereby greatly contributing to a better understanding of MuSK signaling. Impaired MuSK signaling causes severe muscle weakness as described in congenital myasthenic syndromes or myasthenia gravis but the underlying pathophysiology is often unclear. This review focuses on recent advances in deciphering MuSK activation and downstream signaling. We further highlight latest break-throughs in understanding and treatment of MuSK-related disorders and discuss the role of MuSK in non-muscle tissue.