Myasthenia Gravis Patients Research Articles

Dynamic changes of peripheral inflammatory markers link with disease severity and predict short-term poor outcome of myasthenia gravis.

The relationship between peripheral inflammatory markers, their dynamic changes, and the disease severity of myasthenia gravis (MG) is still not fully understood. Besides, the possibility of using it to predict the short-term poor outcome of MG patients have not been demonstrated. This study aims to investigate the relationship between peripheral inflammatory markers and their dynamic changes with Myasthenia Gravis Foundation of America (MGFA) classification (primary outcome) and predict the short-term poor outcome (secondary outcome) in MG patients. The study retrospectively enrolled 154 MG patients from June 2016 to December 2021. The logistic regression was used to investigate the relationship of inflammatory markers with MGFA classification and determine the factors for model construction presented in a nomogram. Finally, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were utilized to evaluate the incremental capacity. Logistic regression revealed significant associations between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), aggregate index of systemic inflammation (AISI) and MGFA classification (p = 0.013, p = 0.032, p = 0.017, respectively). Incorporating dynamic changes of inflammatory markers into multivariable models improved their discriminatory capacity of disease severity, with significant improvements observed for NLR, systemic immune-inflammation index (SII) and AISI in NRI and IDI. Additionally, AISI was statistically associated with short-term poor outcome and a prediction model incorporating dynamic changes of inflammatory markers was constructed with the area under curve (AUC) of 0.953, presented in a nomograph. The inflammatory markers demonstrate significant associations with disease severity and AISI could be regarded as a possible and easily available predictive biomarker for short-term poor outcome in MG patients.

Diurnal cognitive functioning in patients with myasthenia gravis with the role of chronotype and depression: a pilot study.

Myasthenia gravis (MG) is an autoimmune disease manifested by fatigue and weakness of the skeletal muscles. Recent research has indicated that MG patients perform significantly worse than healthy controls in cognitive domains such as attention, verbal fluency, visual learning, and memory. This study aimed to investigate the diurnal fluctuations in cognitive performance in patients with myasthenia gravis in relation to selected clinical and socioeconomic parameters of the disease course, along with the role of chronotype and depression. The participants were recruited from a neurology outpatient clinic. Patients' cognitive functions were assessed twice: in the morning and the evening of the same day. Neuropsychological diagnosis included attention, memory, executive, verbal, and visuospatial abilities. Mood was measured with the Beck Depression Inventory-II and Positive and Negative Affect Schedule. The Morningness-Eveningness Questionnaire was used to examine chronotype. The analyses performed showed no significant differences between subjects and within subjects, apart from semantic fluency. Patients receiving antidepressant treatment obtained better results on attention and working memory tasks. The data obtained show that diurnal neuropsychological performance in MG patients is associated with depression. Routine assessment and treatment of mood disorders could significantly improve cognitive functioning in myasthenia gravis patients.

Safety and efficacy of immune checkpoint inhibitors (ICI) in patients (pts) with pre-existing neurologic autoimmune diseases (NAID) and Parkinson's disease.

2653 Background: Patients with pre-existing NAID often flare with ICIs; neurological (neuro) immune related adverse events (irAEs) are often morbid or fatal, and little is known about safety of ICI in pts with NAID and other neuro conditions (e.g. Parkinson’s). Thus, we aimed to determine their safety and efficacy in these contexts. Methods: We retrospectively analyzed 71 pts from 5 institutions receiving ICIs with NAIDs and Parkinson’s disease. NAIDs included multiple sclerosis (MS), myasthenia gravis (MG), inflammatory neuropathy, transverse myelitis, Lambert-Eaton, myotonic dystrophy, and multifocal motor neuropathy. We collected demographics, cancer outcomes, NAID characteristics, and safety outcomes. We used descriptive statistics to analyze treatment outcomes, NAID flares, and irAEs. Results: We collected 71 pts, 40 with NAID and 31 with Parkinson’s. 24 had melanoma, 12 non-small cell lung cancer (NSCLC), 3 small cell lung cancer (SCLC), 6 urothelial/bladder, 4 renal cell carcinoma, and 22 other; 60 had metastatic and 11 had localized disease. Median age at ICI start was 72 years (61% male, 39% female); 8 received combination ICI and 63 received monotherapy. Of 40 pts with NAID, 30% had either NAID flares or neurologic irAEs and 33% experienced other (non-neuro) irAEs (Table). Toxicities were particularly severe in MG; 70% (n=7) had MG flare/neuro irAE, 3 of which were fatal. In addition, 31 had Parkinson’s; of these, 12.9% (n=4) had Parkinson’s flares, 3% (n=1) had neuro-irAEs, and 42% (n=13) had other irAEs. One pt died of grade 5 myocarditis/myositis following combination ICI (Table). 5 MS patients responded to therapy (23%), but none were those with NAID flare/neuro irAE. Both MG patients who had non-neuro irAEs responded to treatment. Conclusions: In this cohort of ICI treated pts with prior neuro disorders, we demonstrated that MG pts have high rates of MG flare/neuro irAEs, hospitalizations, and fatalities, but low response rates. In contrast, other NAID (particularly MS) as well as Parkinson’s appeared to have modest risks of flares/neuro irAEs. Notably, Parkinson’s pts had high rates of non-neuro irAEs and response rates. [Table: see text]

Physiological and pathological roles of the thymus and value of thymectomy in myasthenia gravis: a narrative review.

Myasthenia gravis (MG) is a well-elucidated autoimmune disorder affecting the neuromuscular junction. Given the relationship between MG and thymic pathologies, with T cell and antibody-mediated pathogenesis, surgical (i.e., thymectomy) and non-surgical approaches remain a mainstay of management of the disease. This review seeks to outline the involvement of the thymus in the development of lymphocytes leading to MG. Different databases were searched exploring the role of thymectomy in treatment and outcomes in various MG patient subpopulations, including in ocular versus generalized disease, different age groups, and antibody status. Overall, the findings of multiple studies and reviews provide evidence to support the efficacy and long-term success of thymectomy in the management of MG; outcomes have included remission status, symptom severity, and need for adjunctive therapy. However, the heterogeneity in the MG population suggests that there are multiple factors that may confound the results of thymectomy and still need further examination. Separately, other autoimmune diseases develop following thymectomy, and further research is required to elucidate this susceptibility. Finally, our review will discuss the different surgical approaches for thymectomy, including their advantages, limitations, and perioperative complications. Overall, in light of the known pathogenesis and association of the thymus with MG, thymectomy remains an extremely effective approach for long-term management and improved clinical outcomes.

Inter-alpha-trypsin inhibitor heavy chain H3 is a potential biomarker for disease activity in myasthenia gravis

Myasthenia gravis is a chronic antibody-mediated autoimmune disease disrupting neuromuscular synaptic transmission. Informative biomarkers remain an unmet need to stratify patients with active disease requiring intensified monitoring and therapy; their identification is the primary objective of this study. We applied mass spectrometry-based proteomic serum profiling for biomarker discovery. We studied an exploration and a prospective validation cohort consisting of 114 and 140 anti-acetylcholine receptor antibody (AChR-Ab)-positive myasthenia gravis patients, respectively. For downstream analysis, we applied a machine learning approach. Protein expression levels were confirmed by ELISA and compared to other myasthenic cohorts, in addition to myositis and neuropathy patients. Anti-AChR-Ab levels were determined by a radio receptor assay. Immunohistochemistry and immunofluorescence of intercostal muscle biopsies were employed for validation in addition to interactome studies of inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3). Machine learning identified ITIH3 as potential serum biomarker reflective of disease activity. Serum levels correlated with disease activity scores in the exploration and validation cohort and were confirmed by ELISA. Lack of correlation between anti-AChR-Ab levels and clinical scores underlined the need for biomarkers. In a subgroup analysis, ITIH3 was indicative of treatment responses. Immunostaining of muscle specimens from these patients demonstrated ITIH3 localization at the neuromuscular endplates in myasthenia gravis but not in controls, thus providing a structural equivalent for our serological findings. Immunoprecipitation of ITIH3 and subsequent proteomics lead to identification of its interaction partners playing crucial roles in neuromuscular transmission. This study provides data on ITIH3 as a potential pathophysiological-relevant biomarker of disease activity in myasthenia gravis. Future studies are required to facilitate translation into clinical practice.

Quantification of saccadic fatigability and diagnostic efficacy for myasthenia gravis.

The diagnostic challenge of myasthenia gravis (MG) is exacerbated by the variable efficacy of current testing methodologies, necessitating innovative approaches to accurately identify the condition. This study aimed to assess ocular muscle fatigue in patients with MG using video-oculography (VOG) by examining repetitive saccadic eye movements and comparing these metrics to those of healthy control participants. This prospective, cross-sectional study was conducted at a tertiary care center and involved 62 patients diagnosed with MG (48 with ocular MG and 14 with generalized MG) and a control group of 31 healthy individuals, matched for age and sex. The assessment involved recording saccadic eye movements within a ± 15° range, both horizontally and vertically, at a rate of 15 saccades per minute over a 5-min period, resulting in 75 cycles. Participants were afforded a 3-min rest interval between each set to mitigate cumulative fatigue. The primary outcome was the detection of oculomotor fatigue, assessed through changes in saccadic waveforms, range, peak velocity, latency, and the duration from onset to target, with a focus on comparing the second saccade against the average of the last five saccades. In the evaluation of repetitive saccadic movements, patients with MG exhibited a reduced saccadic range and a prolonged duration to reach the target, compared to healthy subjects. Furthermore, a significant elevation in the frequency of multistep saccades was observed among MG patients, with a marked rise observed over consecutive trials. Receiver operating characteristic (ROC) analysis revealed the discriminative performance of multistep saccade frequency, in conjunction with variations in saccadic range and duration from onset to target achievement between the second saccade and the mean of the final five saccades, as effective in distinguishing MG patients from healthy subjects. Although alterations in peak saccadic velocity and latency were less pronounced, they were nevertheless detectable. The utilization of VOG for repetitive saccadic testing in the diagnosis of MG has demonstrated considerable diagnostic precision. This methodology affords significant accuracy in evaluating ocular muscle fatigue in MG patients, providing class III evidence supportive of its clinical application.

Diagnostic value of antibody concentration ratio for treatment-refractory myasthenia gravis.

This study aimed to assess the diagnostic potential of the Antibody concentration ratio in identifying treatment-refractory myasthenia gravis (MG). A retrospective analysis was conducted on 116 MG patients who underwent antibody detection at least twice between June 1, 2015, and June 1, 2023. Demographic and clinical characteristics were collated to ascertain their association with refractory MG. The Antibody Concentration Ratio was applied to determine treatment response, using the International Consensus Guidance criteria as the reference standard. The area under nonparametric receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy were calculated to assess the diagnostic efficacy of the Antibody concentration ratio following consecutive immunotherapy relative to initial antibody concentrations for refractory MG. 19 out of 116 patients were unequivocally diagnosed with refractory MG. A significant correlation was found between the Antibody Concentration Ratio and refractory MG status in treatment-refractory and treatment-responsive patients. Subsequently, the AUC demonstrated the robust diagnostic capability of the Antibody concentration ratio for refractory MG, with an AUC of 0.8709 (95% CI: 0.7995-0.9422, p < 0.0001). The optimal cut-off value stood at 0.8903, exhibiting a sensitivity of 94.74% (95% CI: 75.36%-99.73%), a specificity of 68.04% (95% CI: 58.23%-76.48%), and accuracy of 72.41% (95% CI: 64.28%-80.54%). Elevated Antibody Concentration Ratio is intrinsically linked with refractory MG and exhibits potential as an diagnostic biomarker for the condition.

Thymic gene expression analysis reveals a potential link between HIF-1A and Th17/Treg imbalance in thymoma associated myasthenia gravis

Myasthenia gravis (MG) is an immune-mediated disease frequently associated with thymic changes. Increased T helper 17 (Th17) cell activity and dysfunctional regulatory T (Treg) cells have been demonstrated in subgroups of MG. On the other hand, hypoxia-inducible factor 1 (HIF-1) has been shown to regulate the Th17/Treg balance by inducing Th17 differentiation while attenuating Treg development. To identify the underlying mechanisms of different thymic pathologies in MG development, we evaluated thymic samples from thymoma-associated myasthenia gravis (TAMG), MG with hyperplasia (TFH-MG) and thymoma without MG (TOMA) patients. Differential gene expression analysis revealed that TAMG and TFH-MG cells are associated with different functional pathways. A higher RORC/FOXP3 ratio provided evidence for Th17/Treg imbalance in TAMG potentially related to increased HIF1A. The hypoxic microenvironment in thymoma may be a driver of TAMG by increasing HIF1A. These findings may lead to new therapeutic approaches targeting HIF1A in the development of TAMG.

Office-based respiratory assessment in patients with generalized myasthenia gravis

Patients with myasthenia gravis (MG) can present with respiratory dysfunction, ranging from exercise intolerance to overt respiratory failure, increased fatigue, or sleep-disordered breathing. To investigate the value of multiple respiratory tests in MG, we performed clinical and respiratory assessments in patients with mild to moderate generalized disease. One-hundred and thirty-six patients completed the myasthenia gravis quality-of-life score(MG-QOL-15), myasthenia gravis impairment index(MGII), Epworth sleepiness scale(ESS), University of California-San Diego Shortness of Breath Questionnaire(UCSD-SOB), Modified Medical Research Council Dyspnea Scales(MRC-DS), supine and upright forced vital capacity(FVC), maximal inspiratory pressures(MIPs) and sniff nasal inspiratory pressures(SNIP). Seventy-three (54 %) had respiratory and/or bulbar symptoms and 45 (33 %) had baseline abnormal FVC, with no significant postural changes (p = 0.89); 55 (40.4 %) had abnormal MIPs and 50 (37 %) had abnormal SNIPs. Overall, there were low scores on respiratory and disability scales. Females had increased odds of presenting with abnormal FVC (OR 2.89, p = 0.01) and MIPs (OR 2.48, p = 0.022). There were significant correlations between MIPs, FVC and SNIPs; between MGII/MG-QOL15 and UCSD-SOB/MRC-DS and between ESS and respiratory scales in the whole group. Our data suggests that office-based respiratory measurements are a useful screening method for stable MG patients, even when presenting with minimal respiratory symptoms and no significant disability.

A predictive nomogram for short-term outcomes of myasthenia gravis patients treated with low-dose rituximab.

This study aims to establish and validate a predictive nomogram for the short-term clinical outcomes of myasthenia gravis (MG) patients treated with low-dose rituximab. We retrospectively reviewed 108 patients who received rituximab of 600 mg every 6 months in Huashan Hospital and Tangdu Hospital. Of them, 76 patients from Huashan Hospital were included in the derivation cohort to develop the predictive nomogram, which was externally validated using 32 patients from Tangdu Hospital. The clinical response is defined as a ≥ 3 points decrease in QMG score within 6 months. Both clinical and genetic characteristics were included to screen predictors via multivariate logistic regression. Discrimination and calibration were measured by the area under the receiver operating characteristic curve (AUC-ROC) and Hosmer-Lemeshow test, respectively. Disease duration (OR = 0.987, p = 0.032), positive anti-muscle-specific tyrosine kinase antibodies (OR = 19.8, p = 0.007), and genotypes in FCGR2A rs1801274 (AG: OR = 0.131, p = 0.024;GG:OR = 0.037, p = 0.010) were independently associated with clinical response of post-rituximab patients. The nomogram identified MG patients with clinical response with an AUC-ROC (95% CI) of 0.875 (0.798-0.952) in the derivation cohort and 0.741(0.501-0.982) in the validation cohort. Hosmer-Lemeshow test showed a good calibration (derivation: Chi-square = 3.181, p = 0.923; validation: Chi-square = 8.098, p = 0.424). The nomogram achieved an optimal prediction of short-term outcomes in patients treated with low-dose rituximab.

Accuracy of Repetitive Ocular Vestibular-Evoked Myogenic Potentials to Diagnose Myasthenia Gravis in Patients With Ptosis or Diplopia.

We developed repetitive ocular vestibular-evoked myogenic potentials (roVEMP) as an electrophysiologic test that allows us to elicit the characteristic decrement of extraocular muscles in patients with ocular myasthenia gravis (OMG). Case-control studies demonstrated that roVEMP reliably differentiates patients with OMG from healthy controls. We now aimed to evaluate the diagnostic accuracy of roVEMP for OMG diagnosis in patients with ptosis and/or diplopia. In this blinded prospective diagnostic accuracy trial, we compared roVEMP in 89 consecutive patients presenting with ptosis and/or diplopia suspicious of OMG with a multimodal diagnostic approach, including clinical examination, antibodies, edrophonium testing, repetitive nerve stimulation of accessory and facial nerves, and single-fiber EMG (SFEMG). We calculated the roVEMP decrement as the ratio between the mean of the first 2 responses compared with the mean of the sixth-ninth responses in the train and used cutoff of >9% (unilateral decrement) in a 30 Hz stimulation paradigm. Following a complete diagnostic work-up, 39 patients (44%) were diagnosed with ocular MG, while 50 patients (56%) had various other neuro-ophthalmologic conditions, but not MG (non-MG). roVEMP yielded 88.2% sensitivity, 30.2% specificity, 50% positive predictive value (PPV), and 76.5% negative predictive value (NPV). For comparison, SFEMG resulted in 75% sensitivity, 56% specificity, 55.1% PPV, and 75.7% NPV. All other diagnostic tests (except for the ice pack test) also yielded significantly higher positive results in patients with MG compared with non-MG. The study revealed a high sensitivity of 88.2% for roVEMP in OMG, but specificity and PPV were too low to allow for the OMG diagnosis as a single test. Thus, differentiating ocular MG from other neuro-ophthalmologic conditions remains challenging, and the highest diagnostic accuracy is still obtained by a multimodal approach. In this study, roVEMP can complement the diagnostic armamentarium for the diagnosis of MG. This study provides Class I evidence that in patients with diplopia and ptosis, roVEMP alone does not accurately distinguish MG from non-MG disorders. ClinicalTrials.gov: NCT03049956.

Taste disorders and alopecia in myasthenia gravis

BackgroundNon-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.MethodsWe 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.ResultsAmong 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.ConclusionClinicians should be aware of the non-motor symptoms in MG, especially in patients with severe myasthenic symptoms and thymoma-associated MG.

Long-Term Healthcare Resource Utilization and Costs among Patients with Myasthenia Gravis: A Swedish Nationwide Population-Based Study

Introduction: Healthcare costs and societal impact of myasthenia gravis (MG), a potentially life-threatening rare, chronic neuromuscular disease, are sparsely studied. We assessed healthcare resource utilization (HCRU) and associated costs among patients with newly diagnosed (ND) and preexisting (PE) MG in Sweden. Methods: This observational, retrospective cohort study used data from four linkable Swedish nationwide population-based registries. Adult MG patients receiving pharmacological treatment for MG and having ≥24-month follow-up during the period January 1, 2010, to December 31, 2017, were included. Results: A total of 1,275 patients were included in the analysis, of which 554 patients were categorized into the ND MG group and 721 into the PE MG group. Mean (±SD) age was 61.3 (±17.4) years, and 52.3% were female. In the first year post-diagnosis, ND patients had significantly higher utilization of acetylcholinesterase inhibitors (96.0% vs. 83.9%), corticosteroids (59.6% vs. 45.8%), thymectomy (12.1% vs. 0.7%), and plasma exchange (3.8% vs. 0.6%); had higher all-cause (70.9% vs. 35.8%) and MG-related (62.5% vs. 18.4%) hospitalization rates with 11 more hospitalization days (all p < 0.01) and an increased risk of hospitalization (odds ratio [95% CI] = 4.4 [3.43, 5.64]) than PE MG. In year 1 post-diagnosis, ND MG patients incurred EUR 7,302 (p < 0.01) higher total all-cause costs than PE MG, of which 84% were estimated to be MG-related and the majority (86%) were related to inpatient care. These results remained significant also after controlling for baseline demographics and comorbidities (p < 0.01). In year 2 post-diagnosis, the all-cause medical costs decreased by ∼55% for ND MG from year 1 and were comparable with PE MG. Conclusion: In this population-based study, MG patients required significantly more healthcare resources in year 1 post-diagnosis than PE MG primarily due to more pharmacological treatments, thymectomies, and associated hospitalizations. These findings highlight the need to better understand potential factors including disease characteristics associated with increased health resource use and costs and need for more efficacious treatments early in the disease course.

B-cell immune dysregulation with low soluble CD22 levels in refractory seronegative myasthenia gravis.

Myasthenia gravis (MG), primarily caused by acetylcholine receptor (AChR) autoantibodies, is a chronic autoimmune disorder causing severe muscle weakness and fatigability. In particular, seronegative MG constitutes 10%-15% of MG cases and presents diagnostic challenges especially in early-onset female patients who often show severe disease and resistance to immunosuppressive therapy. Furthermore, the immunopathology of seronegative MG remains unclear. Thus, in this study, we aimed to elucidate the pathogenic mechanism of seronegative MG using scRNA-seq analysis and plasma proteome analysis; in particular, we investigated the relationship between immune dysregulation status and disease severity in refractory seronegative MG. Employing single-cell RNA-sequencing and plasma proteome analyses, we analyzed peripheral blood samples from 30 women divided into three groups: 10 healthy controls, 10 early-onset AChR-positive MG, and 10 refractory early-onset seronegative MG patients, both before and after intravenous immunoglobulin treatment. The disease severity was evaluated using the MG-Activities of Daily Living (ADL), MG composite (MGC), and revised 15-item MG-Quality of Life (QOL) scales. We observed numerical abnormalities in multiple immune cells, particularly B cells, in patients with refractory seronegative MG, correlating with disease activity. Notably, severe MG cases had fewer regulatory T cells without functional abnormalities. Memory B cells were found to be enriched in peripheral blood cells compared with naïve B cells. Moreover, plasma proteome analysis indicated significantly lower plasma protein levels of soluble CD22, expressed in the lineage of B-cell maturation (including mature B cells and memory B cells), in refractory seronegative MG patients than in healthy donors or patients with AChR-positive MG. Soluble CD22 levels were correlated with disease severity, B-cell frequency, and RNA expression levels of CD22. In summary, this study elucidates the immunopathology of refractory seronegative MG, highlighting immune disorders centered on B cells and diminished soluble CD22 levels. These insights pave the way for novel MG treatment strategies focused on B-cell biology.

Depression and anxiety among Filipino myasthenia gravis patients seen in a public tertiary hospital in Metro Manila

Anxiety and depression complicate treatment of Myasthenia Gravis (MG) as it overlaps with somatic symptoms related to the disease itself. While both are established factors for disease severity in developed countries, similar research in underdeveloped regions is lacking. This study aims to determine the prevalence of anxiety and depression in patients with MG in a tertiary hospital in the Philippines, and to identify the sociodemographic and illness related factors that affect both mental disorders. Locally validated Hospital Anxiety Depression Scale-Pilipino (HADS-P) questionnaires were administered to 59 consenting MG patients to screen for anxiety and depression. Those who scored more than 8 for each subset of HADS-P were presumed to have anxiety, depression or both. The prevalence of anxiety and depression was 50.9% and 15.3%, respectively. Among the factors analyzed, only the female sex had a significant association with anxiety (p=0.019). The total HADS-P score (p=0.009) and HADS-P score for anxiety (p=0.008) had significant positive correlation with MGFA class. The high prevalence of anxiety and depression in MG warrants proper screening and recognition to institute proper treatment and management. This will also prevent confusion with somatic symptoms associated with MG.

Explainable machine learning model for identifying key gut microbes and metabolites biomarkers associated with myasthenia gravis

Diagnostic markers for myasthenia gravis (MG) are limited; thus, innovative approaches are required for supportive diagnosis and personalized care. Gut microbes are associated with MG pathogenesis; however, few studies have adopted machine learning (ML) to identify the associations among MG, gut microbiota, and metabolites. In this study, we developed an explainable ML model to predict biomarkers for MG diagnosis. We enrolled 19 MG patients and 10 non-MG individuals. Stool samples were collected and microbiome assessment was performed using 16S rRNA sequencing. Untargeted metabolic profiling was conducted to identify fecal amplicon significant variants (ASVs) and metabolites. We developed an explainable ML model in which the top ASVs and metabolites are combined to identify the best predictive performance. This model uses the SHapley Additive exPlanations method to generate both global and personalized explanations. Fecal microbe–metabolite composition differed significantly between groups. The key bacterial families were Lachnospiraceae and Ruminococcaceae, and the top three features were Lachnospiraceae, inosine, and methylhistidine. An ML model trained with the top 1 % ASVs and top 15 % metabolites combined outperformed all other models. Personalized explanations revealed different patterns of microbe–metabolite contributions in patients with MG. The integration of the microbiota-metabolite features and the development of an explainable ML framework can accurately identify MG and provide personalized explanations, revealing the associations between gut microbiota, metabolites, and MG. An online calculator employing this algorithm was developed that provides a streamlined interface for MG diagnosis screening and conducting personalized evaluations.

A Real-life Experience with Eculizumab and Efgartigimod in Generalized Myasthenia Gravis Patients (P4-11.009)

A Real-life Experience with Eculizumab and Efgartigimod in Generalized Myasthenia Gravis Patients (P4-11.009)

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

BackgroundThe 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). MethodsWe 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). ResultsIn 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). ConclusionThe 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.

Social support and medication adherence among adult myasthenia gravis patients in China: the mediating role of mental health and self-efficacy

BackgroundMyasthenia gravis (MG), a rare chronic neuromuscular disorder, is characterized by progressive physical decline and requires long-term pharmacological treatment. Due to the decline of physical and social abilities, MG patients are in great need of social support, including tangible and emotional support. This study aims to examine the association between social support and medication adherence and the possible mediating effects of mental health and self-efficacy among MG patients.MethodsA cross-sectional analysis of a nationwide MG registry was conducted on 865 patients under oral medication treatment in China between June and July 2022. Validated scales were used to measure the respondent’s mental distress (Four-item Patient Health Questionnaire), social support (Modified Medical Outcomes Study Social Support Scale), self-efficacy for medication use (Self-efficacy for Appropriate Medication Use Scale), and medication adherence (Morisky Medication Adherence Scale, MMAS).ResultsThe association between social support and medication adherence and possible mediating effects of mental distress and self-efficacy were tested by structural equation model, with significant demographic and disease-related factors adjusted. The respondents showed a very low level of medication adherence (71.2% poor adherence; 1.4% high adherence; mean MMAS = 4.65). The level of social support was positively associated with medication adherence, and such association was fully mediated by two indirect pathways: through self-efficacy (β = 0.07, proportion mediated = 63.8%); and through mental distress and then self-efficacy (β = 0.01, proportion mediated = 6.7%).ConclusionProvision of social support and interventions on mental health with emphasis on improving self-efficacy for medication use may effectively improve medication adherence among MG patients.

Systemic Inflammatory Response Index, a Potential Inflammatory Biomarker in Disease Severity of Myasthenia Gravis: A Pilot Retrospective Study.

Myasthenia gravis (MG) is a chronic autoimmune disease caused by neuromuscular junction (NMJ) dysfunction. Our current understanding of MG's inflammatory component remains poor. The systemic inflammatory response index (SIRI) presents a promising yet unexplored biomarker for assessing MG severity. This study aimed to investigate the potential relationship between SIRI and MG disease severity. We conducted a retrospective analysis of clinical data from 171 MG patients admitted between January 2016 and June 2021. Patients with incomplete data, other autoimmune diseases, or comorbidities were excluded. Disease severity was evaluated using the Myasthenia Gravis Foundation of America (MGFA) classification and Myasthenia Gravis Activities of Daily Living (MG-ADL) on admission. The association between SIRI and disease severity was assessed through logistic regression analysis, along with receiver operating characteristic (ROC) curve and decision curve analysis (DCA) comparisons with established inflammation indicators. After exclusion, 143 patients were analyzed in our study. SIRI levels significantly differed between patients with higher and lower disease severity (p < 0.001). Univariate logistic regression showed that SIRI had a significant effect on high disease severity (OR = 1.376, 95% CI 1.138-1.664, p = 0.001). This association remained significant even after adjusting for age, sex, disease duration, history of MG medication and thymoma (OR = 1.308, 95% CI 1.072-1.597, p = 0.008). Additionally, a positive correlation between SIRI and MG-ADL was observed (r = 0.232, p = 0.008). Significant interactions were observed between SIRI and immunosuppressor (p interaction = 0.001) and intravenous immunoglobulin (p interaction = 0.005). DCA demonstrated the superior net clinical benefit of SIRI compared to other markers when the threshold probability was around 0.2. Our findings indicate a strong independent association between SIRI and disease severity in MG, suggesting SIRI's potential as a valuable biomarker for MG with superior clinical benefit to currently utilized markers.