Comparison of juvenile and adult myasthenia gravis in a French cohort with focus on thymic histology.

Myasthenia gravis (MG) is an autoimmune disease characterized by muscle fatigability due to acetylcholine receptor (AChR) autoantibodies. To better characterize juvenile MG (JMG), we analyzed 85 pre- and 132 post-pubescent JMG (with a cutoff age of 13) compared to 721 adult MG patients under 40 years old using a French database. Clinical data, anti-AChR antibody titers, thymectomy, and thymic histology were analyzed. The proportion of females was higher in each subgroup. No significant difference in the anti-AChR titers was observed. Interestingly, the proportion of AChR+ MG patients was notably lower among adult MG patients aged between 30 and 40 years, at 69.7%, compared to over 82.4% in the other subgroups. Thymic histological data were examined in patients who underwent thymectomy during the year of MG onset. Notably, in pre-JMG, the percentage of thymectomized patients was significantly lower (32.9% compared to more than 42.5% in other subgroups), and the delay to thymectomy was twice as long. We found a positive correlation between anti-AChR antibodies and germinal center grade across patient categories. Additionally, only females, particularly post-JMG patients, exhibited the highest rates of lymphofollicular hyperplasia (95% of cases) and germinal center grade. These findings reveal distinct patterns in JMG patients, particularly regarding thymic follicular hyperplasia, which appears to be exacerbated in females after puberty.

Economic burden of generalized myasthenia gravis (MG) in the United States and the impact of common comorbidities and acute MG-events.

BACKGROUND: This study assessed the incremental healthcare costs and resource utilization (HRU) associated with generalized myasthenia gravis (gMG), as well as variability in these outcomes among patients with gMG and common comorbidities and acute MG-related events. METHODS: Adults with gMG and without MG were identified from a large US database (2017-2021). The index date was the first MG diagnosis (gMG cohort) or random date (non-MG cohort). Cohorts were propensity score matched 1:1. The gMG cohort included subgroups of patients with a 12-month pre-index (baseline) cardiometabolic or psychiatric comorbidity, or a post-index MG exacerbation/crisis. Monthly healthcare costs (2021 USD) and HRU were compared post-index between gMG and non-MG cohorts. RESULTS: The gMG and matched non-MG cohorts each contained 2,739 patients. Mean incremental healthcare costs associated with MG were $4,155 (gMG: $5,567; non-MG: $1,411), with differences driven by incremental inpatient costs of $2,166 (gMG: $2,617; non-MG: $452); all p < 0.001. The gMG versus non-MG cohort had 4.36 times more inpatient admissions and 2.26 times more outpatient visits; all p < 0.001. Among patients with gMG in cardiometabolic (n = 1,859), psychiatric (n = 1,308), and exacerbation/crisis (n = 419) subgroups, mean monthly healthcare costs were $6,660, $7,443, and $17,330, respectively. CONCLUSIONS: gMG is associated with substantial incremental costs and HRU, with inpatient costs driving the total incremental costs. Costs increased by 20% and 34% among patients with cardiometabolic and psychiatric conditions, respectively, and over three times among those with acute MG-related events. gMG is a complex disease requiring management of comorbidities and treatment options that can prevent acute symptomatic events.

Generalized myasthenia gravis (gMG) is a rare long-standing condition that affects the junctions between nerves and muscles, causing them to be weak. In a serious case, the diaphragm ­ a muscle that helps with breathing ­ becomes so weak that a patient will need a machine to breathe for them. This is called MG exacerbation or crisis. In this study, we used a large insurance database in the United States to look at how much money healthcare payers paid for gMG patients on average and what healthcare resources patients with gMG used. We compared these findings with patients without gMG. Also, among patients with gMG, we reported these findings specifically for patients who also had heart, blood, or blood vessel disease; patients who had a mental illness; and patients who had MG exacerbation or crisis later on. We found that patients with gMG used $5,567 per month on average ($4,155 more than patients without gMG), mostly from overnight hospital stays. Patients with gMG also had four times more overnight hospital stays and two times more hospital day visits when we compared them to patients without gMG. Patients with gMG and other health conditions used even more money and resources per month. Patients with MG exacerbation or crisis used $17,330 per month on average. Our results showed that gMG led to higher healthcare cost and resource use. In order to reduce cost and resources, doctors also need to control for other health conditions as they treat patients with gMG, and to prevent patients from having MG exacerbation or crisis later on.

Epidemiology of myasthenia gravis in France: Incidence, prevalence, and comorbidities based on national healthcare insurance claims data.

BACKGROUND: The European literature has reported high variability in the incidence and prevalence rates of myasthenia gravis (MG), but no specific epidemiological data for France have been published. This study aimed to assess the incidence and prevalence rates of myasthenia gravis in France based on data extracted from the French National Health Insurance Claims Database (the SNIIRAM database). METHODS: We conducted a retrospective repeated cross-sectional population study from 2008 to 2018 using a representative sample of the French population (Échantillon généraliste des bénéficiaires) covered by health insurance. We calculated the incidence, prevalence, and sex ratio of MG and screened for comorbidities associated with MG (standardized to the general population). RESULTS: In total, 331 MG patients were identified between 2008 and 2018. The average incidence of MG in France was 50 per million person-years, while the mean prevalence was 465 per million people. The female-to-male ratio was 1.33. The Incidence of MG gradually increased from 40years of age for women and 60 for men. Thymoma was present for 5.1% of MG patients and a thymectomy was performed for 4.7%. Thyroid disease was the most prevalent autoimmune comorbidity, affecting approximately 8.5% of cases. MG patients had an increased cancer risk, with a standardized rate ratio of 2.38 (95% CI: 1.64-3.46). CONCLUSION: The incidence and prevalence rates of MG are significantly higher than those previously reported in the literature and the incidence increases with age. The excess risk of cancer raises concerns for MG patients, in particular, concerning the management of immunosuppressive drugs.

COVID-19 in patients with myasthenia gravis: a single-center retrospective study in China.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been a great concern since 2019. Patients with myasthenia gravis (MG) may be at higher risk of COVID-19 and a more severe disease course. We examined the associations between COVID-19 and MG. METHODS: This single-center retrospective cohort study involved 134 patients who were diagnosed with MG from June 2020 to November 2022 and followed up until April 2023. They were divided into a COVID-19 group and non-COVID-19 group. Logistic regression analysis was used to detect factors potentially associating COVID-19 with MG. RESULTS: Of the 134 patients with MG, 108 (80.6%) had COVID-19. A higher number of comorbidities was significantly associated with an increased risk of COVID-19 (p = 0.040). A total of 103 patients (95.4%) had mild/moderate COVID-19 symptoms, and 4 patients (3.7%) were severe/critical symptoms (including 2 deaths). Higher age (p = 0.036), use of rituximab (p = 0.037), tumors other than thymoma (p = 0.031), Hashimoto's thyroiditis (p = 0.011), more comorbidities (p = 0.002), and a higher baseline MG activities of daily living (MG-ADL) score (p = 0.006) were risk factors for severe COVID-19 symptoms. The MG-ADL score increased by ≥ 2 points in 16 (15.7%) patients. Dry cough and/or expectoration (p = 0.011), use of oral corticosteroids (p = 0.033), and use of more than one kind of immunosuppressant (p = 0.017) were associated with the increase of the post-COVID-19 MG-ADL score. CONCLUSION: Most patients with MG have a mild course of COVID-19. However, patients with older age, many comorbidities, a high MG-ADL score, and use of a variety of immunosuppressants during COVID-19 may be more prone to severe symptoms.

Ten-year fracture risk in Japanese patients with myasthenia gravis: A comprehensive assessment using the fracture risk assessment tool.

BACKGROUND: Myasthenia gravis (MG) is an immune disorder that causes muscle weakness with an increasing prevalence, particularly among the elderly in Japan. Glucocorticoid treatment for MG is problematic for bone health because of reduced bone density and increased fracture risk. The fracture risk assessment tool (FRAX®) can estimate fracture risk, but its applicability in patients with MG remains uncertain. METHODS: A prospective cohort study was conducted on 54 patients with MG between April and July 2012. Bone mineral density (BMD) was measured, and FRAX® scores were calculated with and without BMD. We also adjusted FRAX® scores based on glucocorticoid dosage. Patients were monitored for major osteoporotic fractures (MOF) until June 2022. Statistical analyses included Kaplan-Meier curves and Cox proportional hazards models. RESULTS: The study group included 12 men and 42 women with a mean age of 62 years. Higher FRAX® scores correlated with increased fracture risk, particularly in the hip and lumbar regions. The 10-year fracture-free rate was significantly lower in the high-FRAX® score group. The FRAX® score using BMD is a significant predictor of MOF risk. The hazard ratio for FRAX® scores was 1.17 (95% CI 1.10-1.26). CONCLUSION: We demonstrated the effectiveness of the FRAX® tool in assessing fracture risk among patients with MG. High FRAX® scores correlated with increased fracture risk, emphasizing its importance. These findings support the incorporation of FRAX® assessment into clinical management to enhance patient care and outcomes. However, the small sample size and observational nature suggest a need for further research.

Taste disorders and alopecia in myasthenia gravis.

BACKGROUND: Non-motor symptoms in myasthenia gravis (MG) are rarely confirmed. Although there are some small cohort studies, a large-systemic survey has not yet been performed. METHODS: We investigated the incidence and clinical characteristics of patients with MG who had taste disorders and alopecia using data of 1710 patients with MG enrolled in the Japan MG Registry 2021. RESULTS: Among them, 104 (6.1%) out of 1692 patients and 138 (8.2%) out of 1688 patients had histories of taste disorders and alopecia, respectively. Among the patients with MG, taste disorders were significantly more common in women, those with severe symptoms, refractory MG, or thymoma-associated MG, and were less common in those with ocular MG. The taste disorders often occurred after the onset of MG and often responded to MG treatments. Alopecia was more common in MG patients with a history of bulbar palsy and thymoma, and it often occurred before the onset of MG and sometimes responded to MG treatments. Multivariate logistic regression analysis revealed taste disturbance was associated with worst quantitative MG score and thymoma-associated MG; and alopecia was associated with thymoma-associated MG. CONCLUSION: Clinicians should be aware of the non-motor symptoms in MG, especially in patients with severe myasthenic symptoms and thymoma-associated MG.

Pregnancy in myasthenia gravis: a retrospective analysis of maternal and neonatal outcome from a large tertiary care centre in Germany.

PURPOSE: Myasthenia gravis (MG) is a rare, potentially life-threatening autoimmune disease with fluctuating muscle weakness frequently affecting women of childbearing age. MG can affect maternal as well as neonatal outcome with risk of worsening of myasthenic symptoms in the mothers and risk of transient neonatal myasthenia gravis (TNMG) and arthrogryposis multiplex congenita (AMC) or foetal acetylcholine receptor antibody-associated disorders (FARAD) in the neonates. METHODS: Retrospective analysis of maternal and neonatal outcome in a cohort of pregnant MG patients treated at a tertiary care centre in Germany. RESULTS: Overall, 66 pregnancies were analysed. During 40 (63%) pregnancies, women experienced a worsening of myasthenic symptoms, of whom 10 patients (15.7%) needed acute therapy with IVIg or plasma exchange. There was no case of myasthenic crisis. Rate of caesarean section was comparable to the overall C-section rate at our centre (38% vs. 40%). However, there was a slightly higher rate for operative vaginal delivery (15% vs. 10%) as potential indicator for fatiguing striated musculature in MG patients during the expulsion stage. Rate of TNMG as well as AMC was 3% (two cases each). CONCLUSIONS: Maternal and neonatal outcome in our cohort was favourable with a low rate of myasthenic exacerbations requiring acute therapies and a low rate of TNMG and AMC/FARAD. Our data might help neurologists and obstetricians to advice MG patients with desire to have children.

Risk of fracture in patients with myasthenia gravis: a nationwide cohort study in Korea.

Myasthenia gravis (MG) is an autoimmune disorder that affects the neuromuscular junctions, resulting in muscle weakness and fatigue. Muscle weakness, restricted mobility, and frequent use of corticosteroids in patients with MG may predispose them to a higher risk of fractures. However, studies on the impact of MG on bone health and the associated fracture risk are scarce. Utilizing claim database of the Korean National Health Insurance Service collected between 2002 and 2020, we compared the risk of major osteoporotic fracture between 23 118 patients with MG and 115 590 individuals as an age- and sex-matched control group using multivariable Cox proportional hazard models. Over a median follow-up duration of 5.58 years, the MG group (mean age 53.7 years; 55% women) had higher risk of major osteoporotic fracture compared with controls (incidence rate 13.59 versus 9.74 per 10 000 person-years), which remained independent of age, sex, comorbidities, drug use including anti-osteoporotic agents, and previous fracture history (adjusted hazard ratio [aHR] 1.19, P < 0.001; subdistributed HR 1.14, P < 0.001 adjusted for mortality as competing risk). Subgroup analyses showed a greater association between MG and major osteoporotic fracture risk in younger (age 50 or younger) than older individuals (aHR 1.34 vs. 1.17) and in men compared with women (aHR 1.32 vs. 1.15; P for interaction < 0.05 for all). An imminent divergence of the fracture risk curve between MG and controls was observed for vertebral fracture, while there was time delay for non-vertebral sites, showing site-specific association. Factors associated with higher fracture risk in patients with MG were older age, female gender, high dose glucocorticoid use (>7.5 mg/day), immunosuppressant use, and previous history of fracture. In summary, patients with MG had higher risk of major osteoporotic fracture compared with controls, which calls further preventive actions in this patient group.

Epidemiology of seropositive myasthenia gravis in Sardinia: A population-based study in the district of Sassari.

INTRODUCTION/AIMS: The global incidence and prevalence of myasthenia gravis (MG) range between 6-31/million and 10-37/100,000, respectively. Sardinia is a high-risk region for different immune-mediated disorders, but the epidemiology of MG remains unclear. We determined the epidemiology of MG with acetylcholine receptor (AChR)-immunoglobulin G (IgG) and muscle-specific tyrosine kinase (MuSK)-IgG in the district of Sassari (North-Western Sardinia; population, 325,288). METHODS: From the laboratory of the University Hospital of Sassari (reference for AChR/MuSK-IgG testing in Sardinia since 1998) and the main neurology units in Sardinia, we retrospectively identified MG patients with (1) AChR-IgG and/or MuSK-IgG positivity by radioimmunoprecipitation assay; and (2) residency in the district of Sassari. Incidence (January 2010-December 2019) and prevalence (December 31, 2019) were calculated. RESULTS: A total of 202 patients were included (incident, 107; prevalent, 180). Antibody specificities were AChR (n = 187 [93%]) and MuSK (n = 15 [7%]). The crude MG incidence (95% confidence interval) was 32.6 (26.8-39.2)/million, while prevalence was 55.3 (47.7-63.9)/100,000. After age-standardization to the world population, incidence decreased to 18.4 (14.3-22.5)/million, while prevalence decreased to 31.6 (26.1-37.0)/100,000. Among incident cases, age strata (years) at MG onset were: <18 (2%), 18-49 (14%), 50-64 (21%), and ≥65 (63%). DISCUSSION: Sardinia is a high-risk region for MG, with a prevalence that exceeds the European threshold for rare disease. Identification of the environmental and genetic determinants of this risk may improve our understanding of disease pathophysiology.

Comorbidity in myasthenia gravis: multicentric, hospital-based, and controlled study of 178 Italian patients.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disorder with fluctuating weakness that causes significant disability and morbidity. Comorbidities may influence the course of MG, particularly in specific subgroups. The aim of this study is to investigate the frequency of comorbidities in MG patients compared to healthy controls (HC) and to evaluate their distribution according to age at disease onset, sex, and disease severity. METHODS: MG patients attending the University Hospital "Paolo Giaccone" in Palermo and "SS Annunziata" Hospital in Chieti were enrolled; HC were enrolled from the general population. Non-parametric statistics and logistic regression were used to assess the association of specific comorbidities according to age at disease onset, sex, disease subtypes, and severity of the disease. RESULTS: A total of 356 subjects were included in the study: 178 MG patients (46% F; median age 60 years [51-71]) and 178 sex- and age-matched HC (46% F, median age 59 years [50-66]). Overall, 86% of MG patients and 76% of HC suffered from comorbidities, and MG patients had a higher number of comorbidities compared to HC. Patients with late-onset suffered from more comorbidities than those with early-onset MG. Hypertension was more common in male patients with MG, while thymic hyperplasia, osteoporosis, and autoimmune diseases were more common in females. Respiratory disorders and thymoma were more common in patients with more severe disease (p < 0.05 for all comparisons). CONCLUSION: MG patients, particularly those with late onset, showed a higher prevalence of comorbidities than HC. Assessment of comorbidities in MG is an essential issue to identify the appropriate treatment and achieve the best management.

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.

Myasthenia gravis concurrent with Parkinson's disease in a Spanish cohort. Causation or correlation?

BACKGROUND: Comorbidity between myasthenia gravis (MG) and other autoimmune diseases is well-documented. However, concurrent MG and Parkinson's disease (PD) have rarely been described. This concurrence has mostly been considered coincidental in cases reported to date. MATERIAL/METHODS: We characterized patients with concurrent MG and PD within a cohort of 631 MG patients by gender, age, MGFA class, quantitative MG score at diagnosis, UPDRS score at diagnosis, and the DaTSCAN uptake pattern, to determine the frequency and the phenotype of individuals with these two concurrent entities. Meta-analysis of cases in the literature was used for comparison with our series. RESULTS: Eighteen cases were identified in which the two diseases were concurrent. The major characteristics of the phenotype are male prevalence, late-onset MG, and frequent initial symptoms of dropped head and oculobulbar involvement. DAT confirmed reduced bilateral uptake in eleven patients and reduced unilateral uptake in the others. CONCLUSIONS: To our knowledge, this is the largest reported series of concurrent MG and PD. This concurrence is more common than expected (2.85%). Either MG or PD may appear first. We found no iatrogenic relationship for the order of appearance. The overlapping of symptoms sometimes leads physicians to overlook the second disease, instead viewing it as a deterioration of the first. This study describes patients with well-documented diagnoses of both MG and PD, thus providing further indications of a shared etiology of these two diseases. Prospective studies including genetic, immunological, and environmental analysis are necessary to identify possible common pathogenic mechanisms.

Burden of disease in Lambert-Eaton myasthenic syndrome: taking the patient's perspective.

BACKGROUND: Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune-mediated neuromuscular disorder leading to muscle weakness, autonomic dysregulation and hyporeflexia. Psychosocial well-being is affected. Previously, we assessed burden of disease for Myasthenia gravis (MG). Here, we aim to elucidate burden of disease by comparing health-related quality of life (HRQoL) of patients with LEMS to the general population (genP) as well as MG patients. METHODS: A questionnaire-based survey included sociodemographic and clinical data along with standardized questionnaires, e.g. the Short Form Health (SF-36). HRQoL was evaluated through matched-pairs analyses. Participants from a general health survey served as control group. RESULTS: 46 LEMS patients matched by age and gender were compared to 92 controls from the genP and a matched cohort of 92 MG patients. LEMS participants showed lower levels of physical functioning (SF-36 mean 34.2 SD 28.6) compared to genP (mean 78.6 SD 21.1) and MG patients (mean 61.3 SD 31.8). LEMS patients showed lower mental health sub-scores compared to genP (SF-36 mean 62.7 SD 20.2, vs. 75.7 SD 15.1) and MG patients (SF-36 mean 62.7 SD 20.2, vs. 66.0 SD 18.). Depression, anxiety and fatigue were prevalent. Female gender, low income, lower activities of daily living, symptoms of depression, anxiety and fatigue were associated with a lower HRQoL in LEMS. DISCUSSION: HRQoL is lower in patients with LEMS compared to genP and MG in a matched pair-analysis. The burden of LEMS includes economic and social aspects as well as emotional well-being. TRIAL REGISTRATION INFORMATION: drks.de: DRKS00024527, submitted: February 02, 2021, https://drks.de/search/en/trial/DRKS00024527 .

Triple-seronegative myasthenia gravis: clinical and epidemiological characteristics.

BACKGROUND: 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. OBJECTIVE: This study aims to describe the frequency and clinical and epidemiological characteristics of patients with triple-SN MG. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

ANTECEDENTES: A Miastenia gravis (MG) é uma desordem autoimune geralmente causada por anticorpos antirreceptores de acetilcolina (anti-RACh), tirosina quinase músculo-específica (anti-MuSK) ou proteína 4 relacionada ao receptor de lipoproteína de baixa densidade (anti-LRP4). No entanto, em uma parcela dos pacientes, nenhum destes três anticorpos pôde ser detectado, sendo estes casos denominados "triplo-soronegativos". OBJETIVO: Descrever a frequência, bem como as características clínicas e epidemiológicas dos pacientes com MG triplo-soronegativa. MéTODOS: Consiste em um estudo transversal e restrospectivo, realizado através da análise de prontuários médicos. Foi realizada análise estatística descritiva e analítica entre os subgrupos de pacientes, classificados de acordo com o perfil sorológico. RESULTADOS: A população consistiu de 93 pacientes com MG: 85 pacientes apresentavam positividade para anticorpos, sendo 80 (86%) com anticorpos anti-RACh, cinco (5,4%) com anti-MuSK, e não foram encontrados pacientes com anti-LRP4. Oito (8,6%) eram pacientes triplo-soronegativos, que apresentaram idade média de início da doença de 30 anos (21-45), e com sintomas iniciais mais comuns de ptose, diplopia e fraqueza generalizada. 75% dos pacientes triplo-soronegativos apresentaram resposta adequada ao tratamento. CONCLUSãO: O estudo demonstrou uma baixa frequência da pacientes com MG triplo-soronegativa na população brasileira. A MG triplo-soronegativa foi predominante nas mulheres, que se apresentaram com ptose, diplopia ou fraqueza generalizada, e a maioria dos pacientes apresentou resposta adequada ao tratamento imunossupressor. Não houve diferença significativa entre a MG triplo-soronegativa e os demais subgrupos.

Autoimmune thyroid disease and myasthenia gravis: a study bidirectional Mendelian randomization.

Background: Previous studies have suggested a potential association between AITD and MG, but the evidence is limited and controversial, and the exact causal relationship remains uncertain. Objective: Therefore, we employed a Mendelian randomization (MR) analysis to investigate the causal relationship between AITD and MG. Methods: To explore the interplay between AITD and MG, We conducted MR studies utilizing GWAS-based summary statistics in the European ancestry. Several techniques were used to ensure the stability of the causal effect, such as random-effect inverse variance weighted, weighted median, MR-Egger regression, and MR-PRESSO. Heterogeneity was evaluated by calculating Cochran's Q value. Moreover, the presence of horizontal pleiotropy was investigated through MR-Egger regression and MR-PRESSO. Results: The IVW method indicates a causal relationship between both GD(OR 1.31,95%CI 1.08 to 1.60,P=0.005) and autoimmune hypothyroidism (OR: 1.26, 95% CI: 1.08 to 1.47, P =0.002) with MG. However, there is no association found between FT4(OR 0.88,95%CI 0.65 to 1.18,P=0.406), TPOAb(OR: 1.34, 95% CI: 0.86 to 2.07, P =0.186), TSH(OR: 0.97, 95% CI: 0.77 to 1.23, P =0.846), and MG. The reverse MR analysis reveals a causal relationship between MG and GD(OR: 1.50, 95% CI: 1.14 to 1.98, P =3.57e-3), with stable results. On the other hand, there is a significant association with autoimmune hypothyroidism(OR: 1.29, 95% CI: 1.04 to 1.59, P =0.019), but it is considered unstable due to the influence of horizontal pleiotropy (MR PRESSO Distortion Test P < 0.001). MG has a higher prevalence of TPOAb(OR: 1.84, 95% CI: 1.39 to 2.42, P =1.47e-5) positivity and may be linked to elevated TSH levels(Beta:0.08,95% CI:0.01 to 0.14,P =0.011), while there is no correlation between MG and FT4(Beta:-9.03e-3,95% CI:-0.07 to 0.05,P =0.796). Conclusion: AITD patients are more susceptible to developing MG, and MG patients also have a higher incidence of GD.

Mendelian randomization analyses of known and suspected risk factors and biomarkers for myasthenia gravis overall and by subtypes.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease that affects neuromuscular junction. The literature suggests the involvement of circulating cytokines (CK), gut microbiota (GM), and serum metabolites (SM) with MG. However, this research is limited to observational trials, and comprehensive causal relationship studies have not been conducted. Based on published datasets, this investigation employed Mendelian Randomization (MR) to analyze the known and suspected risk factors and biomarkers causal association of MG and its subtypes. METHODS: This research used two-sample MR and linkage disequilibrium score (LDSC) regression of multiple datasets to aggregate datasets acquired from the genome-wide association studies (GWAS) to assess the association of MG with 41-CK, 221-GM, and 486-SM. For sensitivity analysis and to validate the robustness of the acquired data, six methods were utilized, including MR-Egger regression, inverse variance weighting (IVW), weighted median, and MR-PRESSO. RESULTS: The MR method identified 20 factors significantly associated with MG, including 2 CKs, 6 GMs, and 9 SMs. Further analysis of the factors related to the two MG subtypes, early-onset MG (EOMG) and late-onset MG (LOMG), showed that EOMG had a high overlap with MG in the intestinal flora, while LOMG had a greater similarity in CKs and SMs. Furthermore, LDSC regression analysis indicated that Peptococcaceae, oxidized biliverdin, and Kynurenine had significant genetic correlations with general MG, whereas EOMG was highly correlated with Intestinibacter, while LOMG had significant genetic associations with Kynurenine and Glucose. CONCLUSION: This research furnishes evidence for the potential causal associations of various risk factors with MG and indicates a heterogeneous relationship between CKs, GMs, and SMs with MG subtypes.

Association between myasthenia gravis and Alzheimer's disease. / Miastenia gravis y enfermedad de Alzheimer: una asociación a estudio.

INTRODUCTION: Myasthenia gravis (MG) and Alzheimer's disease (AD) are two of the most important diseases where the dysregulation of acetylcholine activity plays a crucial role. In the first, this dysregulation happens at the level of the neu-romuscular junction and in the second, in the central nervous system (CNS). AIM: To analyze the possible relationship between these two pathologies, analyzing the prevalence and the odds ratio of AD within patients previously diagnosed with MG. We will compare these data with respect to the prevalence of AD in the general population. PATIENTS AND METHODS: We examined the data obtained by the electronic medical records of patients in the health care system of Castilla La Mancha using the Natural Language Process provided by a clinical platform of artificial intelligence known as the Savana Manager?. RESULTS: We identified 970,503 patients over the age of 60 years, of which 1,028 were diagnosed with MG. The proportion of the patients diagnosed with AD within this group (4.28%) was greater than the rest of the population (2.82%) (p = 0,0047) with an odds ratio of 1.54 (confidence interval at 95% 1.13-2.08; p = 0.0051) without finding significant differences in the bivariate analysis for the rest of the most important actual known risk factors for AD. CONCLUSION: Our results suggest that there might be an increase in the prevalence of AD in patients previously diagnosed with MG.

TITLE: Miastenia gravis y enfermedad de Alzheimer: una asociación a estudio.Introducción. La miastenia gravis (MG) y la enfermedad de Alzheimer (EA) son dos de las enfermedades neurológicas en cuya fisiopatología interviene la acetilcolina en distintos niveles. En la primera, la alteración de este neurotransmisor se produce en la unión neuromuscular, y en la segunda, en el sistema nervioso central. Objetivo. Analizar la posible relación entre dichas patologías estudiando la prevalencia y la odds ratio de la EA dentro de los pacientes diagnosticados de MG con respecto a la prevalencia de EA en la población general. Pacientes y métodos. Se han examinado datos de las historias clínicas electrónicas del sistema de salud de Castilla-La Mancha utilizando el procesamiento de lenguaje natural a través de la plataforma clínica de inteligencia artificial Savana Manager?. Resultados. Se ha identificado a 970.503 pacientes mayores de 60 años, de los que 1.028 tenían diagnóstico de MG. La proporción de pacientes con diagnóstico de EA dentro de este grupo (4,28%) es mayor que en el resto de la población (2,82%; p = 0,0047), con una odds ratio de 1,54 (intervalo de confianza al 95%: 1,13-2,08; p = 0,0051), sin que se encuentren diferencias significativas en el análisis bivariante del resto de los factores de riesgo para EA más importantes conocidos hasta ahora. Conclusiones. Nuestros resultados sugieren que podría existir un aumento de la prevalencia de EA en pacientes con MG.

Myasthenia gravis and five autoimmune diseases: a bidirectional Mendelian randomization study.

BACKGROUND: The association between myasthenia gravis (MG) and other autoimmune diseases is well established. In this study, we aimed to investigate the causal effects between MG and five other autoimmune diseases, including autoimmune thyroid disease (AITD), multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and type 1 diabetes (T1DM). METHODS: We conducted a bidirectional Mendelian randomization (MR) study by using seven published genome-wide association studies (GWAS), including MG (1873 patients versus 36,370 controls), AITD (autoimmune hypothyroidism) (22,997 patients versus 175,475 controls), AITD (autoimmune hyperthyroidism) (962 patients versus 172,976 controls), MS (47,429 patients versus 68,374 controls), RA (14,361 patients versus 43,923 controls), SLE (4222 patients versus 8431 controls), and T1DM (9266 patients versus 15,574 controls). We used the inverse-variance-weighted (IVW) method, weighted-median (WM) estimator, MR-Egger regression, and MR PRESSO in our analyses. We also carried out detailed sensitivity analyses for each direction using the aforementioned methods. RESULTS: When MG was treated as the exposure, MR evidence suggested a causal relationship between MG and T1DM, SLE, AITD (both hypothyroidism and hyperthyroidism), and MS (excluding RA). Using the IVW method, we found that MG was associated with increased risk of T1DM (OR = 1.94; 95% CI, 1.16-3.26; p = 0.012), SLE (OR = 1.47; 95% CI, 1.02-2.13; p = 0.04), AITD (hypothyroidism) (OR = 1.31; 95% CI, 1.02-1.68; p = 0.039), AITD (hyperthyroidism) (OR = 1.55; 95% CI, 1.15-2.09; p = 0.004), and MS (OR = 1.46; 95% CI, 1.01-2.09; p = 0.041). When MG was treated as the outcome, MR evidence suggested that RA, T1DM, and SLE were causal factors in MG. Using the IVW method, we found that the risk of MG increased with exposure to RA (OR = 1.21; 95% CI, 1.08-1.37; p = 0.002), T1DM (OR = 1.09; 95% CI, 1.02-1.16; p = 0.006), and SLE (OR = 1.12; 95% CI, 1.02-1.23; p = 0.018). CONCLUSIONS: This study demonstrated a causal relationship between MG and several other autoimmune diseases. Our results supported a bidirectional causal association between MG and SLE/T1DM. Our findings also provided reliable evidence that MG is associated with increased risk of AITD. Meanwhile, we also showed that RA is a possible causal driver of MG risk.

Environmental factors affecting the risk of generalization for ocular-onset myasthenia gravis: a nationwide cohort study.

BACKGROUND: The environmental effects on the prognosis of ocular myasthenia gravis (OMG) remain largely unexplored. AIM: To investigate the association between specific environmental factors and the generalization of OMG. DESIGN: The cohort study was conducted in China based on a nationwide multicenter database. METHODS: Adult patients with OMG at onset, who were followed up for at least 2 years until May 2022, were included. We collected data on demographic and clinical factors, as well as environmental factors, including latitude, socioeconomic status (per capita disposable income [PDI] at provincial level and education) and smoking. The study outcome was the time to the development of generalized myasthenia gravis (GMG). Cox models were employed to examine the association between environmental exposures and generalization. Restricted cubic spline was used to model the association of latitude with generalization risk. RESULTS: A total of 1396 participants were included. During a median follow-up of 5.15 (interquartile range [IQR] 3.37-9.03) years, 735 patients developed GMG within a median of 5.69 (IQR 1.10-15.66) years. Latitude of 20-50°N showed a U-shaped relation with generalization risk, with the lowest risk at around 30°N; both higher and lower latitudes were associated with the increased risk (P for non-linearity <0.001). Living in areas with lower PDI had 1.28-2.11 times higher risk of generalization. No significant association was observed with education or smoking. CONCLUSIONS: Latitude and provincial-level PDI were associated with the generalization of OMG in China. Further studies are warranted to validate our findings and investigate their potential applications in clinical practice and health policy.