Generalized Myasthenia Gravis Patients Research Articles

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)

Macrophage migration inhibitory factor: A noval biomarker upregulates in myasthenia gravis and correlates with disease severity and relapse

ObjectiveTo explore the relationship between macrophage migration inhibitory factor (MIF) and disease severity and relapse in patients with myasthenia gravis (MG). Methods145 MG patients including 79 new-onset patients, 30 remission patients and 36 relapse patients were enrolled in this study. The detailed characteristics of all enrolled MG patients were routinely recorded, including gender, age, type, MGFA classification, antibody, thymic status, clinical score, treatment, MGFA-PIS and B cell subsets (memory B cells, plasmablast cells and plasma cells) detected by flow cytometry. Serum MIF levels were measured by enzyme-linked immunosorbent assay (ELISA) kit. The correlation of MIF levels with clinical subtypes, disease severity and B cell subsets were investigated. Moreover, logistic regression analysis was applied to assess the factors affecting relapse of generalized MG (GMG). ResultsSerum MIF levels were higher in new-onset MG patients than those in controls and were positively associated with QMG score, MGFA classification and memory B cells. Subgroup analysis revealed that MIF levels were increased in GMG patients than in ocular MG (OMG), as well as elevated in MGFA III/IV compared with MGFA I/II. With the remission of the disease, the expression of serum MIF decreased. The multivariate logistic regression models indicated that high MIF and thymoma was a risk factor for relapse of GMG, and rituximab could prevent disease relapse. ConclusionsMIF can be used as a novel biomarker to reflect disease severity and predict disease relapse in MG patients.

Unveiling Myasthenia Gravis: A Comprehensive Analysis of Diagnostic Tools and Clinical Insights

Objective: This research offers a comprehensive analysis of Myasthenia Gravis (MG), uncovering the remarkable accuracy of spinal accessory, ulnar, and facial nerve repetitive nerve stimulation (RNS), along with the precision of single fiber electromyography (SF-EMG) in MG diagnosis. We also embark on an exploration of clinical features and autoantibody test results in generalized MG patients.
 Methods: In this prospective study, we welcomed 31 individuals definitively diagnosed with generalized MG into our quest. The categorization of patients was conducted in accordance with the criteria set by the Myasthenia Gravis Foundation of America (MGFA). We examined patients' trapezius, nasalis, and abductor digiti minimi (ADM) muscles using RNS. We meticulously recorded the presence of MG autoantibodies, clinical subtypes based on affected muscle groups, and SF-EMG jitter rates.
 Results: The mean age of the 31 patients of whom 19 (61.3%) were male, was 64 ± 13.9 years. Among them, 20 showed positivity in the Anti-AChR antibody test. In 28 patients, accounting for 90.3% of the study group, single fiber electromyography (EMG) displayed increased jitter. There were 4 (12.9%), 24 (77.4%) and 12 (38.7%) patients featuring a decremental response of exceeding 10% in ADM, trapezius and nasalis muscles, respectivelyOur investigation revealed notable findings, such as the absence of substantial correlations between decremental response rates and age, gender, duration of complaints, antibody test results, thymus abnormalities, affected muscle types, familial history, or increased jitter rates in SF-EMG (p>0.05).
 Conclusion: As our findings clearly show, we can confidently attest to the remarkable sensitivity of RNS in MG diagnosis when muscle selection is precise. A gem discovered on our study is the high sensitivity of the spinal accessory nerve, a revelation that should guide the course of routine RNS studies, particularly for those facing ocular-onset myasthenia.

Diaphragmatic ultrasonography as a predictor of respiratory muscle fatigue in myasthenia gravis.

Easy fatigability, the clinical hallmark of generalized myasthenia gravis (GMG), cannot be detected in a dynamic way. The aim of this study was to assess respiratory function dynamically through diaphragmatic ultrasonography (DUS) in GMG patients. GMG patients and controls were recruited in a 1:1 ratio. DUS was performed during one quiet breath and 15 consecutive deep breaths. The diaphragm thicknesses were measured at different positions. Diaphragm thickening fraction (TFdi) and the maximal change in diaphragm thickness (Tmax) during 15 consecutive deep breaths were calculated and transformed to normality, named N-TFdi and N-Tmax, respectively. The percentages of changes in TFdi and Tmax compared with baseline were named ΔTFdi and ΔTmax, respectively. The diagnostic parameter for respiratory muscle fatigue was chosen from ΔTFdi and ΔTmax at different deep breath times according to their ability to distinguish GMG patients from controls and the interrater reliability of TFdi and Tmax. Thirty-four GMG patients and 30 healthy controls were enrolled. N-TFdi and N-Tmax significantly changed as the number of deep breaths increased (p < .001) in GMG patients, but not in controls. ΔTmax of the 15th deep breath (ΔTmax15) was selected as the diagnostic parameter for respiratory muscle fatigue. There were no significant differences in percentage of predicted values of forced vital capacity and arterial partial pressure of carbon dioxide between patients with normal and abnormal ΔTmax15. DUS could identify diaphragm fatiguability in GMG patients, which may be more reliable and sensitive in assessment of diaphragm fatigue than conventional methods.

Study of serum exosome miRNA as a biomarker for early onset adult ouclar myastthenia gravis

BackgroundBy extracting and sequencing miRNAs from serum exosomes of patients with early-onset ocular myasthenia gravis (OMG), generalized myasthenia gravis (GMG) and healthy controls, we screened differentially expressed miRNAs and explored the possibility as potential biomarkers for early-onset OMG. MethodsPeripheral blood samples were collected from patients with early-onset OMG, early-onset GMG, and age-matched healthy subjects, with 6 samples in each group. All these patients were diagnosed as MG for the first time and did not undergo any treatment. Exosomes miRNAs were extracted from the serum and performed deep sequencing; the differentially expressed miRNAs were compared and analyzed between OMG, GMG, and healthy control groups using edgeR. The differential expression standard was set to | log2FC |>1, p < 0.05. Target prediction of mRNAs were performed using miRTarBase, TargetScan, and miRDB databases, and a protein–protein interaction (PPI) network was constructed subsequently. The miRNAs with a significant difference were validated using RT-qPCR (10 early-onset OMG patients, 10 early-onset GMG patients and 10 age-sex-matched healthy subjects), and the value of the area under the ROC curve (AUC) was used to assess the diagnostic accuracy and evaluate clinical prognostic value. ResultsIn total, one upregulated (miR-130a-3p) miRNA was obtained through the upregulated intersection between control vs OMG and OMG vs GMG; four downregulated (miR-4712-3p; miR-6752-5p; miR-320d; miR-3614-3p) miRNAs were obtained through the downregulated intersection between control vs OMG and OMG vs GMG. A total of 408 target genes were predicted for the five differentially expressed miRNAs. The mTOR signaling pathway and Rap1 signaling pathway were significantly enriched based on the enrichment results. RT-qPCR findings revealed that for the OMG, the expression of miR-320d, miR-4712-3p and miR-3614-3p was markedly up-/down-regulated as compared to GMG and healthy control group. The AUC for the three miRNAs between OMG and healthy control groups were 0.78, 0.79 and 0.79 respectively; the AUC between OMG and GMG was 0.84. ConclusionsThe present study identified three novel miRNAs as candidate biomarkers for early-onset OMG patients and it was expected to provide a possibility and a new orientation for serum exosomal miRNAs as OMG diagnostic biomarkers.

A skewed ratio of free light chains is more common in patients with late-onset than early-onset myasthenia gravis

Myasthenia gravis (MG) is an autoantibody-mediated neuromuscular disease with an unpredictable clinical course. Serum free light chains (FLCs) have risen as a promising biomarker for MG, but their role in different subtypes of MG and in predicting disease progression is still uncharted.We investigated plasma from 58 generalized MG patients during post-thymectomy follow-up to determine κ and λ FLC and κ/λ ratio. In a subcohort of 30 patients, we examined the expression of 92 proteins associated with immuno-oncology using Olink. We further studied the ability of FLCs or proteomic markers to differentiate disease severity.Patients with late-onset MG (LOMG) displayed significantly higher mean κ/λ ratio than patients with early-onset MG (P = 0.004). Inducible T-cell co-stimulator ligand (ICOSLG), matrix metalloproteinase 7 (MMP7), hepatocyte growth factor (HGF), and arginase 1 (ARG1) were differentially expressed in MG patients compared to healthy controls. There were no significant associations between clinical outcomes and FLCs or the assayed proteins.In conclusion, an elevated κ/λ ratio suggests long-lasting aberrant clonal plasma cell function in LOMG. Immuno-oncology-related proteomic analysis showed alterations in immunoregulatory pathways. Our findings pinpoint the FLC ratio as a biomarker for LOMG and call for further investigation of the immunoregulatory pathways in MG.

Serum Cytokines Levels in Patients with Myasthenia Gravis and Their Changes After Treatment (P7-8.003)

<h3>Objective:</h3> To evaluate serum levels of Tfh and Th17 related cytokines/molecules in patients with myasthenia gravis (MG). <h3>Background:</h3> The role of cytokines associated with Th1 and Th2 cells in the pathogenesis of myastenia gravis (MG) is well-studied. However, there is no data about the role of Tfh and Th17-related cytokines in MG pathogenesis. <h3>Design/Methods:</h3> Blood samples were collected from generalized MG patients in remission (MG), and from MG patients with myasthenic crisis (cMG) before rescue treatment (plasmapheresis or IVIg) and 24 hours after the last dose/session of the treatment. The disease severity and treatment response were assessed by MGFA classification. Serum levels of IL-21, IL-22, IL-17A, CXCL13, sPD-L1, sICOSLG and sCD40L were analyzed by ELISA. <h3>Results:</h3> Ten MG patients in remission and twelve cMG patients (6 treated with IVIg, 6 with plasmapheresis) were included. CXCL13 levels tended to be lower in MG patients (p=0,056) and it was inversely correlated with disease severity (r=0,429, p&lt;0,05). However, IL-17A levels were significantly higher in cMG patients (p&lt;0,001) and correlated with disease severity (r=0,678, p=0.001). sPDL1, sICOSLG, IL22 levels did not differ between MG and cMG groups. In addition, significant decrease was observed in sPDL1, sICOSLG and CXCL13 serum levels in treated cMG patients (p&lt;0,05), regardless of the treatment method, whereas IL22 levels increased significantly after treatment (p&lt;0,05). <h3>Conclusions:</h3> High serum IL-17A levels seem to contribute to disease severity of MG. Decrease in serum CXCL13 level after treatment may demonstrate its role in myasthenic crisis. Lastly, increase in serum IL-22 levels after treatment, highlight its protective effect in MG. <b>Disclosure:</b> Doruk Arslan has nothing to disclose. Zeynep Ergül Ülger has nothing to disclose. Mrs. Goksen has nothing to disclose. Gunes Esendagli has nothing to disclose. Sevim Erdem-Ozdamar has nothing to disclose. Dr. Tan has nothing to disclose. Can Ebru Kurt has nothing to disclose.

Methotrexate in generalized myasthenia gravis: a systematic review.

Current myasthenia gravis guidelines recommend the use of azathioprine as first-line steroid sparing agent. However, due to its high cost, compliance to azathioprine is low in developing countries. To determine the efficacy and safety of the cheaper methotrexate as an alternative immunosuppressant, Medline/Pubmed, Embase and Cochrane databases and references were searched for clinical trials and observational studies using the search terms: "Myasthenia OR Myasthenia Gravis OR anti AchR antibody positive Myasthenia Gravis OR anti-MuSK antibody Myasthenia Gravis OR MG" AND "Methotrexate". Of 78 possible articles, only 4 were selected using the following eligibility criteria: population: generalized MG patients; intervention: methotrexate; and outcome: effectiveness, steroid sparing efficacy and adverse effects. Two clinical trials and one observational study noted improvement in different MG outcomes in patients given methotrexate. While one randomized controlled clinical trial concluded that methotrexate has no steroid sparing benefit, a single blinded clinical trial established that methotrexate was a better steroid sparing agent than azathioprine starting at 10th month of use. Adverse effects were rare with non-specific pain and elevated transaminases as the most common complaints. Based on available evidence, MTX may be a safe and effective alternative to AZA as steroid sparing agent in developing countries.

Effects of comorbid diseases on clinical outcomes in patients with myasthenia gravis.

This cross-sectional study was undertaken to evaluate the existence and distribution of comorbid disorders among myasthenia gravis (MG) patients according to subgroups and to identify the effects of the comorbid diseases of MG patients on clinical outcomes. The patients were divided into six subgroups according to serum antibodies, age at onset, and thymoma presence. All patients were treated in line with the International Consensus Guidance for Management of Myasthenia Gravis. To assess the clinical outcome after treatment for MG, we used the MGFA Post-intervention Status. In generalized MG patients, the good prognosis group included patients who were classified as having minimal-manifestation status or better. In ocular MG patients, the remission subgroup included patients who were classified as having complete stable remission or pharmacological remission status. Our study included 168 MG patients, 85 were female while 83 were male. Comorbid diseases were present in 124 (73.8%) MG cases. After at least 1year of follow-up, 106 (86.8%) of the generalized MG patients were in the good prognosis group and 16 (13.2%) generalized MG patients were in the poor prognosis group. 27 (58.6%) ocular MG patients were in the remission group and 19 (41.3%) ocular MG patients were in the non-remission group. Hypertension increased the risk of poor prognosis by 3.55-fold among patients with generalized MG and type 2 DM increased the risk of not achieving remission by 9.32-fold among patients with ocular MG. Hypertension and type 2 DM had negative effects on the clinical outcomes of MG.

The Clinical Outcome in AChR-Positive Generalized Myasthenia Gravis: A Retrospective Observational Study.

Myasthenia gravis (MG) is an autoimmune disease affecting the neuromuscular junction, and in over 80% of cases, antibodies are identified against the nicotinic type of acetylcholine receptor (AChR) on the muscle endplate. Despite the availability of various treatment options, patients with MG experience relapses and remission during the course of the disease. Aims and Objective: To understand the clinical profile, predictors of outcomes in acetyl choline receptor (AChR) antibody positive generalized MG. This is a retrospective, single-centre, observational study of 108 patients with AChR positive generalized MG. We collected data on clinical and demographical profiles, treatments received, and treatment responses from those who fulfilled inclusion criteria over a mean follow up period of 33.75 ±7.30 months. Clinical outcomes were studied in terms of the type of remission and crisis or disease exacerbations patients had, considering different variables and treatment received. We found the commonest initial symptoms were ocular or oculo-bulbar, which progressed to generalized MG in the first year of disease onset. 36 (33.3%) patients experienced a crisis requiring mechanical ventilation within a mean period of 9.4 ±4.77 months from the disease onset. Multivariate regression analysis showed late-onset MG (age of onset between 50-70 years) and treatment with rituximab were better correlated with remission, (odd ratio of 4.7; 95 % CI ,1.12 -12.6; P value < 0.05 and odd ratio of 4.56; 95 % CI ,1.2 -10.04; P value < 0.05) respectively. While treatment with Mycofenolate Mofetile (MMF) was associated with a higher number of relapses (odd ratio of 1.8; 95 % CI ,0.08 -0.96; P value < 0.05). Treatment with Rituximab showed a higher rate of remission as compared to treatment refractory (TR) on conventional immunosuppressant therapy (IST). Out of 35(32 %) thymoma patients, 21 patients underwent thymectomy and these patients showed significantly greater rate of remission as compared both thymoma patients who denied thymectomy as a treatment option (N = 10 ;55.60 % vs N = 4; 23.50%). In this study of AChR antibody positive generalized MG patients, we found that nearly one-third of them experienced myasthenic crisis despite receiving the best medical care. Rituximab appeared to be effective in the treatment of refractory MG and those who failed thymectomy. Thymectomy was associated with better outcomes in patients, both with or without a thymoma.

Immunotherapy for ocular myasthenia gravis: an observational study in Japan.

Treatment for ocular myasthenia gravis (OMG) has not yet been well established. Few reports have been published on the clinical practice and outcomes of OMG. We investigated treatment of OMG and its outcomes in Japan.We investigated treatment of OMG and its outcomes in Japan. We performed a retrospective cross-sectional survey of OMG patients from eight hospitals in Japan. Clinical information, including sex, age at onset, initial symptoms, autoantibodies, clinical course, treatment history, complications, and outcomes, was obtained. In addition, we recorded the total number of patients with MG and OMG separately. In total, 135 patients with OMG (67 men, 68 women) were included. Treatment of OMG was not simple and involved various immunotherapeutic strategies. Eight patients went into remission spontaneously without immunotherapy. A total of 117 patients showed improvements after treatment, whereas 10 patients showed refractory responses to treatment. Overall outcomes were good; however, symptoms persisted in 60.7% of patients even after treatment. Among 90 patients who received immunotherapy, only two showed a refractory response. Meanwhile, for 45 patients who did not receive immunotherapy, 8 were refractory. Thus, the rate of refractory disease in the group with immunotherapy was significantly lower (p = 0.001, u-test) than in the group without immunotherapy. The proportion of generalized MG patients among all MG cases was low in medical centers where immunotherapy for OMG was frequently performed. Although the overall prognosis for patients with OMG was good, symptoms remained in more than half of the patients. Immunotherapy, including corticosteroids, may be beneficial for patients with OMG. Is immunosuppressive therapy beneficial for myasthenia gravis patients with ocular symptoms only? Patients with ocular myasthenia gravis (OMG) have only eye symptoms for more than 2 years. Whether this condition is an initial stage of the disease before eventually progressing to generalized myasthenia gravis (gMG) is still uncertain. Different from gMG, OMG is not life-threatening. But eye symptoms often cause troublesome problems in life. Doctors have treated OMG patients similarly to patients with gMG. There is no standard clinical practice for OMG. In this study, we examined how patients with OMG were treated at eight different specialist centers in Japan. In 135 patients with OMG, 8 patients became symptom free without treatment, 117 patients showed improvements after treatment, whereas 10 patients did not get well. Overall outcomes were good, but symptoms remained in 60.7% of patients even after treatment. Among 90 patients who received one or more immunotherapies, only 2 did not get well. Meanwhile, for 45 patients who did not receive immunotherapy, 8 remained ill. We found that treatment of OMG was not simple and often needed multiple immunotherapies. Administering immunotherapy, including corticosteroids, may be beneficial for patients with OMG.

BNT162b2 mRNA COVID-19 Vaccine Three-Dose Safety and Risk of COVID-19 in Patients With Myasthenia Gravis

Objective To study the COVID-19 vaccine three-dose safety and risk of COVID-19 in patients with myasthenia gravis Background Various vaccines, including those against SARS-CoV-2, were reported to trigger or exacerbate myasthenia gravis (MG). As COVID-19 may potentially contribute to the tendency of MG patients to develop respiratory failure, it is important to study the safety of vaccines against SARS-CoV-2 and assess the risk of COVID-19 in MG patients. Design/Methods Among 215 MG patients treated in Tel Aviv Medical Center, 160 were interviewed about their response to the three-dose BNT162b2 mRNA vaccine. We assessed exacerbation rate and safety in a period of up to 6 weeks from each vaccine dose, as well as patient morbidity and mortality during COVID-19 compared to the general population. Results 430 vaccine doses were administered across 150 patients. Thirteen patients (8.7%) complained of exacerbation within 6 weeks (risk period) of each vaccine dose, 8 (5.3%) confirmed by physician report. The exacerbation rates were similar during the risk period (5.6%) compared to corresponding period the previous year (4.8%). MG onset rates during the vaccination period were unaffected compared to previous years. Exacerbation rate among 15 patients who had COVID-19 was significantly higher (40%) compared to rate in the risk period following vaccination, with higher severe or lethal COVID-19 (26.7%) compared to the general population (0.96%), occurring in unvaccinated, steroid-treated, generalized MG patients. Conclusions Three-dose BNT162b2 vaccination is neither associated with exacerbation nor the new onset of MG, whereas COVID-19 is associated with severe disease and death in unvaccinated, steroid-treated generalized MG patients. Hence, it is strongly recommended for generalized MG patients to get vaccinated

Serum Autoantibody Lowering by the Anti-FcRn Monoclonal Antibody, Nipocalimab, Correlates With Clinical Improvement in Generalized Myasthenia Gravis Patients

Objective To evaluate the relationship between clinical improvement in Myasthenia Gravis-Activities of Daily Living (MG-ADL) scores and the pharmacodynamic effects of IgG autoantibody lowering induced by nipocalimab in the Vivacity MG Phase 2 study. Background Nipocalimab is a fully human, aglycosylated, effectorless IgG1 anti-FcRn monoclonal antibody that targets the neonatal Fc receptor (FcRn) with high affinity, thereby lowering IgG pathogenic antibodies in autoimmune disease. Design/Methods The relationship between the reduction in acetylcholine-receptor (AChR)- and Muscle-Specific-Tyrosine-Kinase (MuSK)- autoantibodies with improvement in MG-ADL scores were explored across the four nipocalimab dose arms in the Vivacity MG Phase 2 Study in generalized myasthenia gravis (gMG) patients. Results Of the 68 patients enrolled, 54 were randomized to one of the four nipocalimab dosing arms. 51 (94%) were seropositive for anti-AChR, 3 (6%) for anti-MuSK. Nipocalimab was well-tolerated and achieved substantial, dose-dependent and rapid reductions in serum total IgG, including all IgG subtypes and anti-AChR autoantibodies. These reductions were associated with dose-dependent, durable and rapid MG-ADL responses in all nipocalimab-treated groups. A similar trend in IgG4 reduction was noted, though the sample size of MuSK positive patients was small. Conclusions The results support the rapid, dose-dependent and predictable effect of nipocalimab in lowering pathogenic autoantibodies and inducing clinical improvement in patients with gMG. In addition, the close correlation between serum IgG, anti-AChR and clinical response suggest the potential of using serial serum IgG levels as a biomarker in management of gMG patients treated with nipocalimab; this will be tested in the ongoing Phase 3 gMG trial.

VP.38 A double-blinded, randomized, placebo-controlled phase II study of FcRn antagonist batoclimab in Chinese generalized myasthenia gravis patients

A randomized, double-blind, placebo-controlled, parallel phase II study was conducted for generalized myasthenia gravis (gMG) in Chinese population to evaluate the efficacy and safety of batoclimab as a novel anti-FcRn therapy. Eligible patients were randomized in a 1:1:1 ratio to placebo, batoclimab 340 mg, 680 mg groups, respectively. In double-blinded period, patients received batoclimab or placebo on days 1, 8, 15, 22, 29, and 36. In the open-label period, all patients received batoclimab 340 mgon days 50, 64, and 78. In follow-up period, patients were examined on days 92, 106, and 120. The primary endpoint was myasthenia gravis activities of daily living (MG-ADL) score change on day 43 from baseline. Secondary endpoints included assessment on Quantitative Myasthenia Gravis (QMG), Myasthenia Gravis Composite (MGC), Myasthenia Gravis Quality of Life (MG-QoL), pharmacokinetics, pharmacodynamics and safety events. Totally 30 subjects were randomized, with 9,10 and 11 in the placebo, batoclimab 340mg and 680mg groups respectively.MG-ADL score changes from baseline to day 43 were -2.2±0.9, -4.7±0.6, and -4.4±1.0 in the placebo, batoclimab 340 mg, and 680 mg groups, respectively. Similar changes were observed in QMG, MGC, and MG-QoL scores. The proportion of patients with clinically significant improvement on day 43 was higher in batoclimab groups. In open-label period, symptom recurrence and IgG levels rise again except the former placebo group. On day 120 the placebo group had more improvement compared to batoclimab groups, with IgG levels reaching a plateau. Treatment-emergent adverse events (TEAEs) were comparable among the three groups. No death or TEAEs leading to study discontinuation was observed. The batoclimab groups experienced mild-to-moderate albumin reductions and total cholesterol elevation, all returned to baseline in follow-up without clinical interference. In conclusion, batoclimab is effective and safe in Chinese patients with gMG.

Outcome of thymectomy in myasthenia gravis patients at Neurological Institute of Thailand

Background &amp; Objective: Myasthenia gravis is the most common neuromuscular junction disorders and is caused by autoantibodies against acetylcholine receptors at the postsynaptic muscle endplate. Although thymectomy is current standard treatment but the benefit in long-term outcomes and in non- thymomatous generalized MG patients with negative AChR antibody are still unclear. The objective is to determine the treatment outcomes of thymectomy in non-thymomatous generalized MG patients with or without AChR antibody and identify features related to remission. Methods: Retrospective chart review of the patients diagnosed with non-thymomatous generalized MG from January 1st, 2014 to December 31th, 2018. Patients were classified into two groups: patients with thymectomy (thymectomy group) and patients with no thymectomy (medication group). Results: Seventy-six patients were included. All baseline clinical features, investigations and treatment response were compared. At 6 and 12 months follow up, most patients in both groups had a good response to treatment. At 24 months follow up, ratio of patients in thymectomy group with complete stable remission is higher than in medication group (25% vs. 7.5%) and all patients in this group had positive acetylcholine receptor antibody. The patients in thymectomy group required lower dosage of prednisone, azathioprine and cholinesterase inhibitors than in medication group. Conclusion: Thymectomy was associated with a high probability of achieving remission, reduced cholinesterase inhibitors and immunosuppressive drugs when compared to medication group. Therefore, thymectomy should be strongly considered for non-thymomatous generalized MG patient with positive AChR antibody; and may be considered in non-thymomatous generalized MG patients with negative AChR antibody.

Expression of TRAF6 in peripheral blood B cells of patients with myasthenia gravis

BackgroundTumor necrosis factor receptor-associated factor 6 (TRAF6) can regulate the activation of inflammatory signaling pathways by acting as an E3 ubiquitin ligase, which enhances B cell activation. This study aimed to evaluate the expression of TRAF6 in the peripheral blood B cells of myasthenia gravis (MG) patients and analyze the relationships between TRAF6 expression and clinical characteristics.MethodIn our study, the expression level of TRAF6 in peripheral blood B cells of 89 patients was measured by flow cytometry compared with that of healthy subjects. The effects of disease severity, MG classification and immunotherapy on TRAF6 expression level were also analyzed.ResultsIn our study, TRAF6 expression was elevated in CD19+ B cells and CD19+CD27+ memory B cells in generalized MG (GMG) patients compared with ocular MG (OMG) patients (p = 0.03 and p = 0.03, respectively). There was a significant positive correlation between the TRAF6 expression level and disease severity in both OMG patients and GMG patients (CD19+ B cells: OMG: p < 0.001, r = 0.89; GMG: p = 0.001, r = 0.59; CD29+CD27+ B cells: OMG: p = 0.001, r = 0.80; GMG: p = 0.048, r = 0.38). TRAF6 expression was significantly elevated in CD19+ B cells and CD19+CD27+ memory B cells in GMG with acute aggravation compared with GMG in MMS (p = 0.009 and p = 0.028, respectively). In the eleven MG patients who were followed, TRAF6 expression in B cells and memory B cells was significantly decreased after treatment (p = 0.03 and p < 0.01, respectively).ConclusionTRAF6 is potentially a useful biomarker of inflammation in patients with MG, and might be used to evaluate the effectiveness of treatment.

BNT162b2 mRNA COVID-19 vaccine three-dose safety and risk of COVID-19 in patients with myasthenia gravis during the alpha, delta, and omicron waves.

COVID-19 affects the respiratory parenchyma and may potentially contribute to the tendency of myasthenia gravis (MG) patients to develop respiratory failure. It is, therefore, important to study the safety of vaccines against SARS-CoV-2 and to assess the risk of COVID-19 in MG patients. The safety of the three-dose BNT162b2 mRNA vaccine and outcomes of COVID-19 during the alpha, delta, and omicron waves were studied in MG patients as well as the rate of exacerbations and safety for a period of up to 6 weeks from each vaccine dose and patient morbidity and mortality during COVID-19 compared to the general population. 430 vaccine doses were administered across 150 patients. Thirteen patients (8.7%) complained of exacerbation within 6 weeks of each vaccine dose. Both MG onset rate and exacerbation rate were similar to previous years. MG exacerbation rate among fifteen patients who had COVID-19 was significantly higher (40%) compared to the rate following vaccination. During the alpha and delta waves, COVID-19 mortality and severe disease were significantly higher (26.7%) compared to the general population (0.96%). All of them were unvaccinated and had generalized MG. During the omicron wave, all the MG patients who contracted COVID-19 were vaccinated and had mild disease. We concluded that COVID-19 is hazardous for generalized MG patients, while the vaccination did not raise the risk for either exacerbation or new onset of MG and was associated with a reduced risk for severe COVID-19. Hence, it is recommended for generalized MG patients to get vaccinated.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00415-022-11303-8.

Changes in the amplitude decremental response to repetitive nerve stimulation following fast‐acting treatment in patients with myasthenia gravis during hospitalization

Objectives The aim was to determine the amplitude changes in repetitive nerve stimulation (RNS) decrement values after fast-acting treatments (FTs), including plasmapheresis, high-dose intravenous methylprednisolone and intravenous immunoglobulin, in patients with myasthenia gravis (MG). Methods We retrospectively enrolled 41 patients with MG who received RNS after FT. The median, ulnar, facial, accessory and axillary nerves were tested. An improvement in the quantitative MG score of ≥3 or in the MG activities of daily living scale score of ≥2 was used to define clinical improvement posttreatment. A decrement of ≥10% was defined as abnormal. Results Among 41 enrolled patients (ocular type 13 and generalized type 28), 22 (53.7%) showed clinical improvement after treatment. Among generalized MG patients, the proportion of improvement of abnormal RNS decrement in the proximal muscles, including frontalis, trapezius and deltoid, was significantly greater in the group with clinical improvement than in the group without clinical improvement (46.7% vs 0%, P = 0.005). Logistic regression analysis showed that the quantitative myasthenia gravis score at admission and improvement in abnormal amplitude decrement were associated with a response to FT (P = 0.015 and P = 0.045, respectively). Conclusions The changes in amplitude decrements detected by RNS reflected the therapeutic effect of FT in patients with generalized MG. RNS responses in the proximal muscles might be potentially useful as an objective measure of improvement after aggressive immunotherapy in patients with MG during hospitalization.

Lymphoplasma Exchange Improves Myasthenia Gravis Exacerbations: A Retrospective Study in a Chinese Center.

BackgroundLymphoplasma exchange (LPE), a technique combining plasma exchange with leukapheresis, is emerging as promising treatment for autoimmune diseases. Data on the efficacy and safety of LPE in myasthenia gravis (MG) therapy are scarce. In this study, we aimed to comprehensively review the clinical efficacy, safety, and immunological characteristics of LPE therapy in MG patients.Study Design and MethodsA Chinese cohort of 276 generalized MG patients in state of exacerbation, including impeding crisis, myasthenia crisis, and preparation for thoracic exsection between January 2014 and December 2020, were evaluated in this study.ResultsA total of 276 patients with a median age of 45.5 ± 16.7 years underwent a total of 635 LPE sessions. Clinical scales of Quantitative Myasthenia Gravis (QMG) scores, Myasthenia Gravis Specific Manual Muscle Testing (MMT) scores, activities of daily living (ADL) scores, and quality of life (QOL) scores were improved during 4 weeks’ follow-up. Adverse effects occurred in 20 out of 276 patients, with 14 patients having one adverse event each. Independent predictive factors for good response to LPE therapy were symptom onset before LPE therapy ≤3 days and age on LPE therapy <50 years of age. LPE decreased the serum levels of antibodies, immunoglobulins, and complements 4 weeks after the first replacement, with decreased levels of interleukin (IL)-17A and interferon (IFN)-γ and increased level of IL-10.ConclusionLPE is an effective treatment for MG patients in state of exacerbation and preparation for thymectomy. Early use of LPE on early-onset MG may have good therapeutic effects. The potential mechanism for LPE is the polarization of cytokines from IL-17A, IFN-γ, into IL-10.

Generalized myasthenia gravis patients infected with COVID-19 should continue eculizumab

Eculizumab, a humanized monoclonal antibody, is a complement inhibitor indicated for refractory generalized myasthenia gravis (MG). However, there are limited data on the safety of eculizumab for MG during coronavirus disease 2019 (COVID-19) infection. We report a case in which eculizumab was continued for MG after contracting COVID-19, followed by a favorable outcome.