Myasthenia Gravis Patients Research Articles

C-reactive protein/albumin ratio as a prognostic biomarker in myasthenia gravis

Aims: Limited research has explored novel inflammatory targets in myasthenia gravis (MG). This study aimed to investigate the role of the C-reactive protein (CRP)/albumin ratio (CAR) in disease activity and prognosis in MG patients. Methods: CRP, albumin, and CAR levels were compared between MG patients and healthy controls. The relationships of these parameters with MG activities of daily living (MG-ADL) scores and mortality were examined. Results: Sixty-six patients and 51 controls participated. CRP and CAR levels were significantly higher in the patient group (p=0.002, 0.003). No significant difference was found in albumin levels (p=0.154). A positive correlation was observed between the MG-ADL stage and both CRP and CAR levels (p=0.000 for both), with these markers increasing as MG-ADL worsened. A negative correlation was found between the MG-ADL stage and albumin (p=0.003). CRP, CAR, and albumin levels were significantly associated with mortality (p=0.000, 0.000, 0.005). Conclusion: Elevated CRP and CAR levels in MG patients suggest acute inflammation contributing to clinical decline. Albumin’s decrease with worsening MG-ADL suggests its value as a prognostic marker rather than a diagnostic. CAR proved to be a stronger marker than albumin for disease diagnosis, severity monitoring, and mortality prediction. Our findings could help illuminate inflammatory mechanisms in MG and other neuromuscular diseases.

Seasonal variation in myasthenia gravis incidence.

Environmental factors may contribute to myasthenia gravis (MG) development, sometimes with seasonal patterns of exposure. However, whether seasonality has an impact on MG incidence remains unclear. We aimed to investigate the association between seasonality and MG onset. We reviewed data of MG patients with acetylcholine receptor (AChR)-IgG and disease onset between January 2010-December 2019, from two Italian cohorts: 1) an hospital-based cohort and 2) a population-based cohort. MG cases were assigned to four season-trimesters based on month of onset to determine seasonal association with MG incidence. We enrolled 316 patients:214 in the hospital-based and 102 in the population-based cohort. Median age at onset was 66years (range, 8-92); Female accounted for 41.1%. The median number of new MG cases per season-trimester was significantly higher in summer than other trimesters (p=0.009), and associated with higher environmental temperatures. Our findings suggest that MG onset may be more common in summer and at higher environmental temperatures. Identifying the determinants of this association may improve our understanding of disease pathophysiology.

Sirt6, Deubiquitinated and Stabilised by USP9X, Takes Essential Actions on the Pathogenesis of Experimental Autoimmune Myasthenia Gravis by Regulating CD4+ T Cells.

Myasthenia gravis (MG) presents with symptoms that significantly affect patients' daily lives. Long-term MG therapies may lead to substantial side effects, predominantly due to prolonged immune suppression. Sirt6, which plays a vital role in maintaining cellular homeostasis and is recognised for its involvement in cytokine production in immune cells, has not yet been explored in relation to MG. PBMCs and CD4+ T cells were isolated from blood samples. RT-qPCR, western blot and ELISA were used to assess the expression of target genes and proteins. Flow cytometry was used to identify the subsets of T helper cells. Co-IP was conducted to investigate the interaction between USP9X and Sirt6. Finally, the experimental autoimmune myasthenia gravis (EAMG) model was established. In MG patients, Sirt6 levels were downregulated compared to healthy controls. Sirt6 overexpression led to a reduction in Th1 and Th17 cell populations while augmenting Treg cells in PBMCs. USP9X interacted with Sirt6, leading to its deubiquitination and stabilisation. Elevated Sirt6 levels subsequently mitigated symptoms in the EAMG model. The stabilisation of Sirt6, mediated by USP9X, has been found to relieve symptoms of EAMG by influencing the subtypes of T helper cells. This highlights the promising potential of Sirt6 as a viable therapeutic target in the treatment of MG.

Short-term and long-term prognoses in AChR-Ab positive very-late-onset myasthenia gravis patients.

Very-late-onset myasthenia gravis (VLOMG) refers to myasthenia gravis (MG) with onset at age 65 or older. Current research on VLOMG prognosis remains limited, especially regarding factors influencing outcomes. To identify the clinical factors that affect the short- and long-term prognosis of MG patients with an onset age ⩾65 years. This was a single-center, retrospective cohort study of AChR-ab positive VLOMG patients, classified into two subgroups based on age of onset: sub-very-late-onset MG (S-VLOMG, onset age ⩾65 and <75 years), and super-late-onset MG (SLOMG, onset age ⩾75 years). A total of 93 patients were included, including 75 in the S-VLOMG group and 18 in the SLOMG group. Clinical, therapeutic, and prognosis data were reviewed, and the Cox regression model was used to identify factors influencing short- and long-term prognosis. Patient characteristics were well balanced between the groups. Overall, 49.5% of patients achieved minimal symptom expression (MSE) within 6 months and 86% within 24 months. There was no significant difference between the groups in the proportion achieving MSE at 6 months (p = 0.635) or 24 months (p = 0.714). The median time to achieve MSE was also comparable between the S-VLOMG and SLOMG groups (199.0 days vs 280.5 days, p = 0.463). Low baseline MG-ADL score and steroid therapy were associated with better short-term prognosis (p = 0.007 and p = 0.002, respectively). For long-term prognosis, baseline bulbar and limb involvement, time to treatment initiation, and use of immunosuppressants were significant factors (p = 0.025, p = 0.004, p = 0.025, and p < 0.0001, respectively). There were no significant differences in side effects or drug withdrawal rates between two groups. This study demonstrated that AChR-ab positive VLOMG patients have a favorable prognosis and responded well to medication, with age and comorbidities showing no significant impact.

The impacts of the COVID-19 pandemic on Australia's myasthenia gravis patients: A self-reported survey study.

Previous studies have demonstrated high morbidity and mortality in patients with myasthenia gravis (MG) who acquired COVID-19. We aimed to identify the impact of the pandemic on MG disease control, treatment and quality of life. A prospective observational cohort study was conducted to identify the impact of the COVID-19 pandemic on Australian patients with MG. We conducted an online survey through Myasthenia Alliance Australia from May 2022 to July 2022. Among the 229 patients who responded to the survey, most patients had three (80; 34.9%) or four (116; 50.7%) doses of the COVID-19 vaccines, 65 (28.4%) had contracted COVID-19, with 6 patients (9.4%) requiring hospitalisation. A large proportion of patients responded that the pandemic had no impact on their MG disease control (123; 53.7%) or treatment (111; 48.5%). Most patients felt the pandemic had either a mild (111; 48.5%) or moderate (50; 21.8%) impact on their mood. Our study provides a snapshot of the types of impacts experienced by myasthenic patients during the pandemic, in particular the psychosocial effects. As we continue to live with COVID-19, clinicians should consider its various impacts in the holistic management of their patients.

Diabetes mellitus in patients with myasthenia gravis: a systematic review and meta-analysis.

With the prolongation of life expectancy in patients with myasthenia gravis, the number of comorbidities is increasing. Diabetes mellitus is one of the main comorbidities faced by patients with myasthenia gravis. However, there is not enough epidemiological information on diabetes mellitus. Given these limitations, the purpose of this study was to review the prevalence of diabetes mellitus in patients with myasthenia gravis and whether the myasthenia gravis is associated with an increased risk of gestational diabetes mellitus. PubMed, Embase, and Web of Science were searched for articles published prior to February 2024. Endnote 21 software was used to manage all relevant records. Review Manager version 5.4 and Stata version 18.0 software were used for the statistical analysis. Funnel plots and Egger's test were used to assess publication bias. Twenty-four articles met the inclusion criteria and were included in the study. Among 23,516 myasthenia gravis patients, the prevalence of diabetes mellitus was 17% (95% CI 12~22%). In addition, the meta-analysis of the two studies showed that myasthenia gravis was significantly associated with an increased risk of gestational diabetes mellitus (OR = 1.56, 95% CI 1.26~1.93, p < 0.01). Among the comorbidities of myasthenia gravis patients, diabetes mellitus is common, and the risk of gestational diabetes mellitus is increased in myasthenia gravis patients. These findings remind us that diabetes mellitus seems to be an important issue in the clinical management of myasthenia gravis patients and requires more attention.

Cutoffs on severity metrics for minimal manifestations or better status in patients with generalized myasthenia gravis

International consensus guidance and Japanese clinical guidelines for myasthenia gravis (MG) recommend achieving minimal manifestations or better status (MM-or-better) as the severity component of the treatment goal. However, the subjective nature of determining MM can result in ambiguity regarding this category in clinical practice and clinical trials. This study analyzed severity metrics in a large number of MG patients to propose criteria for MM-or-better. We utilized data obtained from 3800 MG patients who participated in nationwide cross-sectional surveys in Japan. Among these, 2784 patients with generalized MG were divided into two groups based on MG Foundation of America postintervention status: MM-or-better status (n = 1432); and improved-or-worse (I-or-worse) status (n = 1352). We compared severity metrics (MG-activities of daily living scale [MG-ADL], quantitative MG score [QMG], and MG composite scale [MGC]) between groups and calculated cutoff values to separate the two groups. Using these cutoffs, patients subjectively assigned as MM-or-better were classified into strict MM-or-better (below a cutoff) or optimistic MM-or-better (above a cutoff) groups, and clinical characteristics were then compared. Cutoff values for strict MM-or-better were MG-ADL ≤2, QMG ≤7, and MGC ≤4 (sensitivity 82.0%, 88.7%, and 87.4%; specificity 85.0%, 70.0%, and 77.9%; and accuracy 91.2%, 88.7%, and 90.7%, respectively). Mean values of the revised 15-item MG quality of life scale were significantly lower in the strict MM-or-better group than in the optimistic MM-or-better group. Quantitative criteria for MM-or-better appear likely to be useful in the context of rigorous clinical trials and also as reference information in clinical settings.

Myasthenia Gravis Misunderstood - Identifying the historical misinterpretations, miscommunication, and misconceptions

Myasthenia Gravis (MG) is a serious disease and can present clinically with very severe symptoms in many patients; however, the fluctuating severity of MG results in the disease being commonly misdiagnosed as other conditions, including conversion disorder. The earliest recorded literature on MG provides evidence of the variability of signs and symptoms, including many patients who appeared to have mild symptoms initially but died suddenly and unexpectedly from MG. Often, these patients were initially believed to be suffering from hysteria. This review analyzes some of the most prominent MG literature still cited today. It found that many communication errors have led to today’s misunderstandings and have continued to cause difficulties in diagnosis and difficulty in understanding the MG patients’ lived experiences. These errors include the intended meaning for ‘gravis’ being misinterpreted as ‘severe’ instead of the intended meaning of ‘a painful weight in the limbs’, the false belief that ‘gravis’ is Latin for ‘grave’ and how the miscommunication of the early 1900’s MG autopsy studies added to this confusion, where MG continued to be referred to as a ‘grave’ condition. The continued omission of the sensory symptoms associated with MG from the literature has also been miscommunicated for decades, however such symptoms are now becoming recognized as a result of increasing patient led research. Myasthenia Gravis should continue to be regarded as a serious disease, due to the devastating effect on quality of life for many people, and the unpredictability of the myasthenic crisis potentially occurring in all people living with MG, including those who are undiagnosed. The dismissing of mild symptoms results in many MG patients remaining undiagnosed. The possibility that individuals in this group go on to become victims of Sudden Adult Unexplained Death (SUD) is yet to be investigated, and there is a need for research in this area. Miscommunication also includes omitting ‘old knowledge,’ not listening to the patient’s lived experience, and failing to integrate relevant interdisciplinary knowledge. Good examples of these are The Mary Walker Effect, and combining patient lived experience with ocular anatomy and physiology knowledge to develop new MG-specific ocular motility clinical tests. A new test is presented for evaluating MG eye signs utilizing knowledge of the ‘Safety Factor,’ and is referred to as The SLOWLY Test (Significant Level Of Weakness, Loci in Y Axis). Awareness of the historical misinterpretations, miscommunications, and misconceptions is crucial to preventing delay in diagnosis in MG patients, developing new clinical tests, rehabilitation interventions, and helping doctors and others understand the lived experience of MG patients

AChR-blocking antibodies and complement system dynamics: evaluating their interplay and clinical implications in myasthenia gravis.

Myasthenia gravis (MG) is an autoimmune disorder characterised by autoantibodies (abs) targeting proteins at the neuromuscular junction, primarily the acetylcholine receptor (AChR). While the role of AChR-binding abs is well-established, the pathogenicity and clinical relevance of AChR-blocking antibodies in MG, and their association with complement system, remain less understood. This study aims to provide comprehensive insights into the prevalence and interplay of AChR-blocking antibodies and the complement system in an Argentinian MG cohort, investigating their relationships with disease activity. We studied 75 MG patients with detectable AChR-binding abs, assessing the presence of AChR-blocking abs and complement components C3, C4, and C5a. We also examined clinical severity using the Activities of Daily Living and MG Composite scores. Correlation analyses were made to elucidate associations. AChR-blocking abs were detected in 49.3% of the patients. An inverse correlation was found between AChR-blocking abs titres and disease severity, with a higher titre associated with milder symptoms. Complement analysis revealed higher C4 levels in the AChR-blocking abs positive group, indicating reduced complement activation. Our study provides valuable insights into the prevalence of AChR-blocking antibodies. Higher AChR-blocking abs titres were associated with less severe MG and reduced complement system activation, indicating a potential protective mechanism for those abs. These findings suggest that AChR-blocking abs could serve as a potential biomarker for a milder disease course and highlight the need for further research to understand their role in MG pathology, which will improve strategies for clinical management and diagnosis.

Medical costs of treating myasthenia gravis in patients who need intravenous immunoglobulin (IVIg) – a register-based study

BackgroundSeveral innovative treatments are expected for myasthenia gravis (MG) in the coming years. Healthcare payers usually require cost-effectiveness analyses before reimbursement. We aimed to investigate resource utilization and direct medical costs for patients with MG treated with intravenous immunoglobulin (IVIg) to inform such analyses.MethodsWe identified patients with MG in the Norwegian Patient Registry based on at least two hospital encounters with an MG diagnosis (ICD-10 G70.0) from 1 Jan 2010 to 31 Dec 2021. IVIg treatment was identified by medical procedure and Anatomical Therapeutic Chemical (ATC) codes (RPGM05 and J06BA02). Using Diagnosis-Related Group (DRG) cost weights, we estimated direct medical costs for each year following the first MG diagnosis.ResultsOver the study period, 1083 patients were diagnosed with MG in Norway, of whom 155 (14.3%) were treated with IVIg. No significant differences in age or sex were observed between IVIg and non-IVIg patients. Compared with non-IVIg patients, IVIg-patients had 2.3 times higher direct medical costs during the first year after MG diagnosis (EUR 35,714 vs. EUR 15,457) and 3.1 times higher costs during the second year (EUR 19,119 vs. EUR 6256). In the fifth year after diagnosis, IVIg-patients still had higher costs and resource utilization than non-IVIg patients (EUR 9953 vs. EUR 5634).ConclusionIVIg treatment represents an important marker for high direct medical costs among patients with MG. The costs continue to be high during the first five years after MG diagnosis.

Impact of SARS-CoV-2 infection on patients with myasthenia gravis: a retrospective study in a Chinese population.

Myasthenia gravis (MG) is characterized by fluctuating muscle weakness due to immune-mediated damage to acetylcholine receptors. Viral infections can exacerbate symptoms of muscle weakness, and the clinical status of patients with MG may influence the outcomes of such infections. Here, we identified factors of symptom exacerbation, severe SARS-CoV-2 infection, and pneumonia in patients with MG who are infected with SARS-CoV-2. The clinical characteristics and outcomes of 341 MG patients infected with SARS-CoV-2 across multiple regions in China were determined. The median age of the patients was 49 years (range: 35-60 years) and the median disease duration was 4 years (range: 2-8 years). Among the patients, 67 (49.0%) were male and 174 (51.0%) were female. Multivariate analysis indicated that thymectomy [OR, 1.654 (95% CI, 1.036-2.643); p = 0.035], severe SARS-CoV-2 infection [OR, 4.275 (95% CI, 2.206-8.286); p < 0.001], and pyridostigmine bromide [OR, 1.955 (95% CI, 1.192-3.206); p = 0.008] were associated with exacerbation of MG symptoms in patients infected with SARS-CoV-2. Age was significantly associated with severe SARS-CoV-2 infection [OR, 1.023 (95% CI, 1.001-1.046); p = 0.008], while patients with cardiac/vascular comorbidities exhibited an increased likelihood of severe SARS-CoV-2 infection [OR, 3.276 (95% CI, 1.027-10.449); p = 0.045]. Likewise, steroid treatment [OR, 6.140 (95% CI, 2.335-16.140); p < 0.001] was associated with a significantly increased likelihood of severe SARS-CoV-2 infection compared with symptomatic treatment. Additionally, gender [OR, 0.323 (95% CI, 0.120-0.868); p = 0.025] and SARS-CoV-2 severity [OR, 6.067 (95% CI, 1.953-18.850); p = 0.002] were associated with the occurrence of pneumonia. We identified factors that were associated with the exacerbation of MG symptoms in patients infected with SARS-CoV-2, including thymectomy, severe SARS-CoV-2 infection, and the use of pyridostigmine bromide. Due to the retrospective nature of the study, these findings should be interpreted as associations rather than predictive factors. However, the results confirm the established relationships between severe SARS-CoV-2 infection and age, cardiovascular comorbidities, and the use of steroid treatment, suggesting that these factors should be considered when managing MG patients during SARS-CoV-2 infection.

HLA Class I and II Alleles in Anti-Acetylcholine Receptor Antibodies Positive and Double-Seronegative Myasthenia Gravis Patients of Romanian Descent.

Background: Several significant associations between certain Human Leukocyte Antigen (HLA) alleles and myasthenia gravis (MG) subtypes were established in populations from Western Europe and North America and, to a lesser extent, from China and Japan. However, such data are scarcely available for Eastern Europe. This study aimed to analyze the associations of HLA Class I and II alleles with MG and its serological subtypes (with anti-acetylcholine receptor autoantibodies, RAch+MG, and double-seronegative, dSNMG) in myasthenic patients of Romanian descent. Methods: We consecutively enrolled adult Romanian unrelated myasthenic patients, which were genotyped by next-generation sequencing for HLA-A, -B, -C, -DRB1 and -DQB1. The descent-matched controls were represented by two separate groups of random normal subjects genotyped for the main five HLA loci at the two-digit and four-digit levels, respectively, collected from the Allele Frequency Net Database. Results: A total of 40 patients (females: 80.00%; median age at onset: 42.5 years, range: 1-78; RAch+MG: 75.00%; dSNMG: 22.50%) were included. We were able to confirm previously acknowledged allelic associations: positive for HLA-B*08, DRB1*14:54 and DRB1*16:01 and negative for DRB1*13. However, we found some potential novel significant positive associations between MG and the HLA-A*02:36, B*47, B*73, B*44:27 and B*57:02 alleles. All alleles positively associated with MG remained significantly associated with RAch+MG, regardless of the patients' clinical and thymic heterogeneity. We found significant positive associations between dSNMG and the HLA-B*47, B*44:27 and DRB1*14:54 alleles that are shared with RAch+MG. Conclusions: These results suggest both distinct and common etiopathogenic mechanisms between dSNMG and RAch+MG. Our study pioneers allele associations in Romanian MG patients.

The telemedical platform MyaLink for remote monitoring in myasthenia gravis – rationale and protocol for a proof of concept study

Rationale: Myasthenia gravis (MG) is a rare, chronic neurological disorder leading to fluctuating muscle weakness and potentially life-threatening crises. Patients often require life-long specialized treatment, but timely interventions are frequently hindered by the limited availability of specialists. Telemedical solutions at specialized centers enabling patient-physician interaction hold promise in bridging this gap, but are not yet available for MG. We developed ‘MyaLink,’ a remote monitoring platform tailored for MG, and outline the study design assessing the platform and clinical outcomes regarding telemedical intervention. Additionally, we present study results on care-related aspects in MG prior to telemedical intervention to identify challenges in the current care provision process. Design: The platform comprises a patient app and a physician portal, enabling systematic symptom monitoring using data from patient-reported outcome measures (PROMs), coupled devices and a communication module. The randomized controlled study included 45 study participants (SP) over a 12-weeks period, including a group receiving standard care (15 MG patients) and a group with additional telemedical treatment (30 MG patients) including assessment of PROMs, wearable data collection and telemedical check-ups. Questions regarding care-related aspects were assessed at baseline visit. Results: Many SP (N = 33, 73.3%) communicate with the physician managing their MG via email. 73.3% (N = 33) of SP identify areas for improvement in their MG care including symptom monitoring (N = 23, 69.7%), specialist appointment availability (N = 22, 66.7%), medication (N = 22, 66.7%) and specialist accessibility (N = 20, 60.6%). Additionally, 73.3% (N = 33) reported that the effort required to manage their MG was high. Conclusion: Our results emphasize the high demand of affected MG patients for continuous telemedicine services. MyaLink can provide such a service through personalized support based on the exchange of health data. Telemedicine solutions such as MyaLink promise to improve myasthenia care by providing accessible, patient-centred care that enables early detection of worsening symptoms and non-response to treatment. Trial registration: The study was registered under DRKS00029907 on August 19, 2022.

HHV-6B, HHV-7, and B19V Are Frequently Found DNA Viruses in the Human Thymus but Show No Definitive Link with Myasthenia Gravis.

Myasthenia gravis (MG) is a rare autoimmune disorder characterised by muscle weakness resulting from autoantibody-mediated disruption of the neuromuscular junction. Notably, it is also frequently associated with thymic pathology. This study explores the relationship between MG and DNA viruses in the thymus, employing targeted NGS and qPCR to analyse thymic tissue samples from both MG patients and healthy controls. We detected HHV-6B, HHV-7, EBV, and B19V across various tissue groups. However, no significant enrichment of these viruses was observed in the thymic tissue of MG patients. Additionally, we confirmed a dormant persistence of B19V within the thymus of seropositive individuals. These findings indicate that DNA viruses are unlikely to serve as primary environmental triggers for MG.

Decreased serum IL-16 and increased serum TSG-14 levels in myasthenia gravis

Background: Myasthenia gravis (MG) is an autoimmune disease characterized by an imbalance between inflammatory mediators and immune cells. The diagnosis and assessment of disease severity require the aid of more specific biomarkers. Methods: Utilizing the Luminex assay, we quantified the serum levels of CD137, galectin-9, MMP12, TSG14, IL-16, IL-31, and IL-34 in a cohort of 157 participants, which comprised 98 patients with MG and 59 healthy controls (HCs). Correlation analyses were performed to examine the relationship between serum IL-16 and TSG-14 levels and clinical outcomes. Results: Serum levels of IL-16 were significantly lower in MG patients compared to the HC group (median [inter-quartile range (IQR)], 102.1 [73.58–126.7] pg/mL versus 162.4 [95.72–312.7] pg/ mL, P &lt; 0.0001). Conversely, the serum concentration of TSG-14 was significantly higher in MG patients than in HCs (1249 [809.3–2134] pg/mL versus 883.0 [512.5–1264] pg/mL, P = 0.0035). No significant differences were observed in the serum levels of CD137, galectin-9, IL-31, IL-34, and MMP12 between MG patients and HCs. Correlation analysis revealed a negative correlation between serum IL-16 levels and Quantitative Myasthenia Gravis (QMG) scores, as well as Activities of Daily Living (ADL) scores; TSG-14 displayed a positive correlation with QMG scores. Conclusion: Serum IL-16 concentrations were reduced, whereas TSG-14 concentrations were elevated in MG patients. These findings suggest that these serum proteins can potentially serve as biomarkers for assessing disease severity in MG patients.

SPOON: an observational, cross-sectional study of perceptions and expectations of adults with generalised myasthenia gravis in France

ObjectivesTo capture patient perceptions about living with myasthenia gravis (MG) with respect to aspirations and ways to improve treatment.DesignOnline patient survey.SettingPatients recruited by MG patient associations or at MG reference...

Tocilizumab for the management of corticosteroid-resistant GO combined with OMG: a case series

PurposeTo highlight the safety and efficacy of tocilizumab (TCZ) in Graves’ ophthalmopathy (GO) combined with ocular myasthenia gravis (OMG) patients refractory to steroids and cholinesterase inhibitor (CEI).MethodsThis was retrospective case series. We reviewed the health records of patients with GO combined with OMG, ten of whom were refractory to corticosteroids and CEI treatment and received intravenous injection of TCZ. Ten patients were treated with four injections of TCZ (intravenously, 8 mg per kilogram of body weight, once a month). We analyzed the efficacy and safety of TCZ treatment for this subset of patients with GO and OMG.ResultsThe main outcomes including quality of life questionnaire in Graves’ orbitopathy (GO-QoL) score, Clinical Activity Score (CAS), Myasthenia Gravis Activities of Daily Living profile (MG-ADL) score, proptosis, diplopia and ptosis were assessed at 3 time points: “Baseline” (before the TCZ injection), “4th month” (after fourth time TCZ injection), “Follow up” (Last follow-up). Comparing parameters at 4th month vs. at baseline, all indicators improved at 4th month including GO-QoL score of visual functioning subscale (82.29 ± 13.71 vs. 35.98 ± 20.66, P < 0.001), GO-QoL score of the appearance subscale (80 ± 8.75 vs. 40.63 ± 17.95, P < 0.001), CAS (1.3 ± 0.46 vs. 4.5 ± 0.81, P < 0.001), MG-ADL (2.5 ± 1.56 vs. 5.11 ± 1.14, P < 0.001). Furthermore, proptosis decreased from 19.73 ± 2.84 to 17.93 ± 2.26 mm at 4th month (P < 0.0001). Diplopia and ptosis were also resolved at 4th month. After following up for a minimum of 11 months, the patients had no signs of relapse. In addition, we observed that all analyzed patients exhibited no significant drug reactions following the administration of TCZ.ConclusionTocilizumab maybe a useful therapeutic option in refractory GO coexisting with OMG. However, considering the limitation of a retrospective study, short follow up period and small sample size of this study, randomized controlled studies are needed to validate our results.

Frequency of upper respiratory tract infections in patients with myasthenia gravis compared to the general population

IntroductionPatients with myasthenia gravis (MG) undergoing immunomodulating therapies are at an increased risk of serious infections. However, the risk of developing self-limited infections, particularly upper respiratory tract infections (URTI), remains unclear. This study aimed to determine the frequency of URTI among patients with MG compared to the general population and to identify potential predisposing factors. MethodsA monthly questionnaire was administered to patients with MG and a control group over a period of 6 months. The questionnaire assessed the presence of URTI symptoms within the previous month. Statistical analysis was conducted using a chi-square or Fischer exact test, as appropriate. ResultsThe study included 161 participants (50 MG patients and 111 control subjects). The frequency of URTI was comparable between the MG group (70 %) and controls (82 %) (p = 0.09). Among patients with MG, a higher proportion of patients who received rituximab developed URTI (93 %) than those who did not (61 %), P = 0.04. ConclusionThe frequency of URTI was similar in patients with MG compared to the general population. Due to the small sample size and several other limitations, further research is warranted to validate these findings and explore associations between rituximab and URTI.

Efgartigimod treatment in patients with anti-MuSK-positive myasthenia gravis in exacerbation.

The prevalence of patients positive for muscle-specific kinase antibody (hereafter, MuSK-Ab) accounts for 5-8% of all myasthenia gravis (MG) cases. Currently, efgartigimod has shown good therapeutic effects in MUSK-Ab-positive MG patients in a phase III clinical trial. However, phase III clinical trials tend to exclude MG patients in exacerbation, and there are only few real-world studies on the efficacy of efgartigimod in MuSK-Ab-positive myasthenic crisis (MC) patients. This retrospective, real-world study aimed to explore the efficacy of efgartigimod in MuSK-Ab-positive MG with exacerbation. We reviewed the clinical data of four MuSK-Ab-positive patients with exacerbation of MG who received efgartigimod at the First Affiliated Hospital of Sun Yat-sen University, including two patients with MC. All patients were admitted between September 2023 and May 2024. Most patients are simultaneously undergoing rituximab treatment. Each patient completed one cycle of efgartigimod. After the first administration, four patients showed a clinically meaningful decrease in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score (a reduction of more than 4 points compared to baseline), and all patients showed a decrease in IgG levels after one cycle of efgartigimod. Regarding safety, none of the patients experienced any obvious adverse effects. At the final follow-up, all patients achieved the minimal symptom expression status (an MG-ADL score of 0 or 1) following the first administration of efgartigimod for 8.75 ± 5.56 weeks. This article presents a case involving a patient who exhibited prompt alleviation of symptoms following the administration of a high dose of efgartigimod (20 mg/kg, given on days 1 and 5), without the use of any other fast-acting treatment. This retrospective real-world study demonstrates the effectiveness and safety of efgartigimod in these four MuSK-Ab-positive, female Asian patients with exacerbation of MG, as well as in patients experiencing MC. It is important to note that efgartigimod should not be viewed as a substitute for foundational immunotherapy; rather, it is intended as a rescue treatment during exacerbations and as an adjunctive therapy in the context of long-term immunotherapy. This non-invasive approach has the potential to become another treatment option for MuSK-Ab-positive MG patients.

Induction cyclophosphamide with maintenance immunosuppression in high-risk myasthenia gravis: long-term follow-up and safety profile

BackgroundPatients with refractory or high-risk myasthenia gravis (MG) respond poorly to conventional immunosuppressive therapy, requiring rescue therapies and often experiencing treatment toxicity. Rescue and injectable therapies do not induce remission...