Myasthenia Gravis Exacerbation Research Articles

Association between COVID-19 vaccination and myasthenia gravis: A population-based, nested case-control study.

Existing data regarding the link between COVID-19 vaccine and myasthenia gravis (MG) are scarce. We aimed to assess the association between Pfizer-BioNTech vaccine with both new-onset MG and MG exacerbation. For the first aim, we conducted a nested case-control study in a cohort of 3,052,467 adults, without a diagnosis of MG, from the largest healthcare provider in Israel. Subjects were followed from January 1, 2021 until June 30, 2022 for the occurrence of MG. Ten randomly selected controls were matched to each case of new-onset MG on age and sex. For the second aim, a nested case-control study was conducted in a cohort of 1446 MG patients. Four randomly selected MG patients (controls) were matched to each case of MG exacerbation. Exposure to COVID-19 vaccine in the prior 4 weeks was assessed in cases and controls. Overall, 332 patients had new-onset MG and were matched with 3320 controls. Multivariable conditional logistic regression models showed that the odds ratio (OR) for new-onset MG, associated with COVID-19 vaccine, was 1.14 (95% CI 0.73-1.78). The results were consistent in sensitivity analysis that used more stringent criteria to define MG. Overall, 62 patients with MG exacerbation were matched to 248 MG controls. The multivariable OR for MG exacerbation, associated with COVID-19 vaccine, was 1.35 (95% CI 0.37-4.89). All results were similar when the prior exposure to COVID-19 vaccine was extended to 8 weeks. This study suggests that Pfizer-BioNTech vaccine is not associated with increased risk of new-onset nor exacerbation of MG.

A decentralized, prospective, observational study to collect real-world data from patients with myasthenia gravis using smartphones.

We conducted a 3-month, prospective study in a population of patients with Myasthenia Gravis (MG), utilizing a fully decentralized approach for recruitment and monitoring (ClinicalTrials.gov Identifier: NCT04590716). The study objectives were to assess the feasibility of collecting real-world data through a smartphone-based research platform, in order to characterize symptom involvement during MG exacerbations. Primary data collection included daily electronically recorded patient-reported outcomes (ePROs) on the presence of MG symptoms, the level of symptom severity (using the MG-Activities of Daily Living assessment, MG-ADL), and exacerbation status. Participants were also given the option to contribute data on their physical activity levels from their own wearable devices. The study enrolled and onboarded 113 participants across 37 US states, and 73% (N= 82) completed the study. The mean age of participants was 53.6 years, 60% were female. Participants were representative of a moderate to severe MG phenotype, with frequent exacerbations, high symptom burden and multiple comorbidities. 55% of participants (N=45) reported MG exacerbations during the study, with an average of 6.3 exacerbation days per participant. Median average MG-ADL scores for participants during self-reported exacerbation and non-exacerbation periods were 7 (interquartile range 4-9, range 1-19) and 0.3 (interquartile range 0-0.8, range 0-9), respectively. Analyses examining relationships between patient-reported and patient-generated health data streams and exacerbation status demonstrated concordance between self-reported MG-ADL scores and exacerbation status, and identified features that may be used to understand and predict the onset of MG symptom exacerbations, including: 1.) dynamic changes in day-to-day symptom reporting and severity 2.) daily step counts as a measure of physical activity and 3.) clinical characteristics of the patient, including the amount of time since their initial diagnosis and their active medications related to MG treatment. Finally, application of unsupervised machine learning methods identified unique clusters of exacerbation subtypes, each with their own specific representation of symptoms and symptom severity. While these symptom signatures require further study and validation, our results suggest that digital phenotyping, characterized by increased multidimensionality and frequency of the data collection, holds promise for furthering our understanding of clinically significant exacerbations and reimagining the approach to treating MG as a heterogeneous condition.

Clinical Characteristics of Myasthenia Gravis Patients with COVID-19 in Guangxi, China: A Case-Control Study.

With the adjustment of prevention strategies in December 2022, coronavirus disease 2019 (COVID-19) became widely prevalent in China. This study is aimed to describe the clinical characteristics of myasthenia gravis (MG) patients with COVID-19 and identify risk factors of exacerbation in MG patients with COVID-19 in Guangxi. A total of 489 MG patients and 587 control subjects in Guangxi during the COVID-19 pandemic were enrolled in this case-control study. After contacting the participants, the clinical data of MG patients and the control group were analyzed. The clinical characteristics of MG patients with COVID-19 were described. Multivariable logistic regression analysis was used for discovering independent risk factors of MG exacerbation in the patients with MG and COVID-19. A total of 311 (75.30%) MG patients and 428 (72.91%) control subjects were infected with COVID-19, and 64.31% of MG patients with COVID-19 were women. The median age at the time of interview was 41 (IQR: 28, 54) years old, and median onset age was 36 (IQR: 24, 51), both of which were lower than those in MG patients without COVID-19. MG duration was 24 (IQR: 9, 72) months. About 44.69% of patients were generalized MG (GMG). About 11.90% of MG patients with COVID-19 showed severe COVID-19 symptoms and the duration of symptomatic COVID-19 was 9.57 ± 6.79 days, higher than those in the control group. About 35.69% MG patients with immunosuppressive drugs were infected with COVID-19, which is higher than those in the non-infected MG patients (21.57%). A total of 120 (38.59%) MG patients with COVID-19 had comorbidities. About 21 (20.19%) of the 104 MG patients without vaccination showed severe COVID-19 symptoms. Multivariable logistic regression analysis showed that baseline MG activities of daily living profile (MG-ADL, OR 1.280, 95% CI: 1.010-1.621, p = 0.041), duration of COVID-19 (OR 1.158, 95% CI: 1.100-1.220, p < 0.001), GMG (OR 2.331, 95% CI: 1.228, 4.426, p = 0.010), and lack of COVID vaccination (OR 2.075, 95% CI: 1.152, 3.738, p = 0.015) were independent factors of exacerbation in MG patients with COVID-19. MG patients with immunosuppressive drugs, younger onset, longer MG duration, or comorbidities are more susceptible to COVID-19. The baseline MG-ADL, duration of symptomatic COVID-19, GMG, and lack of COVID-19 vaccination are independent risk factors of exacerbation in MG patients with COVID-19.

COVID-19 infection in myasthenia gravis: Clinical course and outcomes.

Myasthenia gravis (MG) patients have been predicted to have high rates of coronavirus disease-2019 (COVID-19) complications due to frequent involvement of respiratory muscles in MG and frequent use of immunosuppressive therapies. We investigated outcomes of MG patients infected with SARS-CoV-2 to identify risk factors for exacerbation and severe disease. This was a retrospective analysis of 39 MG patients with SARS-CoV-2 infection from January March 1, 2020 to October 25, 2021 at Emory University. Patients' records were queried for demographic data, MG history, and COVID-19 treatments and hospitalizations. At the time of infection, 8 of 39 were vaccinated, 30 of 39 unvaccinated, and 1 unknown. Average age was 52.6 years. Twenty-seven patients were receiving immunomodulatory treatments at the time of infection. Thirty-five of 39 were symptomatic, 21 were hospitalized, and 7 required ventilations. MG exacerbations occurred in 5 and were treated with therapeutic plasma exchange (n = 1), intravenous immunoglobulin (IVIg) (n = 1), and prednisone taper (n = 5). Four hospitalized patients died from COVID-related lung injuries. No deaths were attributed to MG exacerbation; however, one patient receiving IVIg for MG exacerbation had a pulmonary embolism. There were no deaths in fully vaccinated patients, and only one vaccinated patient was admitted to the intensive care unit. High rates of COVID-19 complications and death were observed in this cohort of MG patients. Some patients with MG and COVID-19 also had an exacerbation during infection. Further studies are needed to determine whether MG patients are at higher risk for complications than the rest of the population.

Fatal triad of checkpoint inhibitors: Pembrolizumab induced myasthenia gravis with myositis and myocarditis in a patient with thymoma

Pembrolizumab is an immune checkpoint inhibitor that acts by blocking programmed cell death proteins, however, its use is limited in patients with thymoma. We describe a 31-year-old woman with thymoma who developed myocarditis, myositis and exacerbation of myasthenia gravis due to use of pembrolizumab. There were elevations of creatine phosphokinase, troponin T, CK-MB, alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase. Electrophysiologic studies showed a myopathic pattern and more than 10% decremental response on repetitive nerve stimulation. Steroid and intravenous immunoglobulin treatment was initiated. Because of a lack of improvement she received 5 cycles of plasma exchange. The patient benefited significantly from plasmapheresis and was discharged with noninvasive mechanical ventilation after one hundred and fifteen days of hospitalization. Plasmapheresis in the early period can be an effective treatment option in patients who develop severe neurological symptom with use of checkpoint inhibitors.

Clinical and immune-related factors associated with exacerbation in adults with well-controlled generalized myasthenia gravis.

To describe the clinical predictors and immune-related factors for exacerbation in adults with well-controlled generalized myasthenia gravis (GMG). We conducted a retrospective analysis of 585 adults with well-controlled GMG from our institution to explore the risk factors for exacerbation. Furthermore, propensity score matching (PSM) was used to compare the proportions of lymphocyte subsets, and the levels of immunoglobulin, complement, and anti-acetylcholine receptor antibody (AChR-ab) in the peripheral blood of 111 patients with exacerbations and 72 patients without exacerbations. A total of 404 patients (69.1%) experienced at least one exacerbation, and the median (interquartile range) time to the first exacerbation was 1.5 years (0.8-3.1 years). Multivariable Cox regression analysis showed that age at onset, disease duration before enrollment, Myasthenia Gravis Foundation of America classification (MGFA) class III vs. class II, MGFA class IV-V vs. class II, AChR-ab levels, anti-muscle specific kinase antibody levels, thymus hyperplasia, prednisone plus immunosuppressants vs. prednisone treatment, and thymectomy were independent predictors for exacerbations [hazard ratio (HR) = 1.011, 1.031, 1.580, 1.429, 2.007, 2.033, 1.461, 0.798, and 0.651, respectively]. Propensity-matched analysis compared 51 patient pairs. After PSM, the peripheral blood proportions of CD3-CD19+ B cells, ratios of CD3+CD4+/CD3+CD8+ T cells, and AChR-ab levels were significantly increased, and the peripheral blood proportions of CD3+CD8+ T and CD4+CD25+CD127low+ regulatory T cells (Tregs) were significantly lower in patients with exacerbation than in those without exacerbation (all p < 0.05). Myasthenia gravis (MG) exacerbations were more frequent in those patients with older onset age, longer disease duration, more severe MGFA classification, positive AChR-ab, and lack of combined immunotherapy or thymectomy treatment. On the other hand, CD3-CD19+ B cells, CD3+CD8+ T cells, Tregs, and AChR-ab in peripheral blood may be involved in the course of GMG exacerbation.

Outcomes of COVID-19 Infection and Vaccination Among Individuals With Myasthenia Gravis

There are limited data regarding COVID-19 outcomes and vaccine uptake and safety among people with myasthenia gravis (MG). To investigate COVID-19-related outcomes and vaccine uptake among a population-based sample of adults with MG. This population-based, matched cohort study in Ontario, Canada, used administrative health data from January 15, 2020, and August 31, 2021. Adults with MG were identified using a validated algorithm. Each patient was matched by age, sex, and geographic area of residence to 5 controls from the general population and from a cohort of individuals with rheumatoid arthritis (RA). Patients with MG and matched controls. Main outcomes were COVID-19 infection and related hospitalizations, intensive care unit admissions, and 30-day mortality among patients with MG vs controls. Secondary outcomes were uptake of COVID-19 vaccination among patients with MG vs controls. Among 11 365 233 eligible Ontario residents, 4411 patients with MG (mean [SD] age, 67.7 [15.6] years; 2274 women [51.6%]) were matched to 22 055 general population controls (mean [SD] age, 67.7 [15.6] years; 11 370 women [51.6%]) and 22 055 controls with RA (mean [SD] age, 67.7 [15.6] years; 11 370 women [51.6%]). In the matched cohort, 38 861 of 44 110 individuals (88.1%) were urban residents; in the MG cohort, 3901 (88.4%) were urban residents. Between January 15, 2020, and May 17, 2021, 164 patients with MG (3.7%), 669 general population controls (3.0%), and 668 controls with RA (3.0%) contracted COVID-19. Compared with general population controls and controls with RA, patients with MG had higher rates of COVID-19-associated emergency department visits (36.6% [60 of 164] vs 24.4% [163 of 669] vs 29.9% [200 of 668]), hospital admissions (30.5% [50 of 164] vs 15.1% [101 of 669] vs 20.7% [138 of 668]), and 30-day mortality (14.6% [24 of 164] vs 8.5% [57 of 669] vs 9.9% [66 of 668]). By August 2021, 3540 patients with MG (80.3%) vs 17 913 general population controls (81.2%) had received 2 COVID-19 vaccine doses, and 137 (3.1%) vs 628 (2.8%), respectively had received 1 dose. Of 3461 first vaccine doses for patients with MG, fewer than 6 individuals were hospitalized for MG worsening within 30 days of vaccination. Vaccinated patients with MG had a lower risk than unvaccinated patients with MG of contracting COVID-19 (hazard ratio, 0.43; 95% CI, 0.30-0.60). This study suggests that adults with MG who contracted COVID-19 had a higher risk of hospitalization and death compared with matched controls. Vaccine uptake was high, with negligible risk of severe MG exacerbations after vaccination, as well as evidence of effectiveness. The findings support public health policies prioritizing people with MG for vaccination and new COVID-19 therapeutics.

Myasthenia Gravis Exacerbation Following COVID-19 Vaccine: A Case Report

Background: Vaccination remains the mainstay of strategy for prevention of Coronavirus Disease-2019 (COVID-19). AZD1222 (AstraZeneca vaccine) was distributed in Sudan by the COVID-19 Vaccines Global Access facility in March 2021. It was added to the emergency use list by the WHO in mid-February 2021. However, vaccine safety among patients with autoimmune diseases, such as myasthenia gravis (MG), is yet to be established. MG is a relatively rare illness that could result in life-threatening complications. Myasthenic crisis is considered the most serious complication of MG that can lead to death due to aspiration and respiratory failure. The case: We report the case of a 37-year-old Sudanese female who presented to the emergency room with an exacerbation of her normally well-controlled MG following her second dose of AZD1222 vaccination. She continued to deteriorate and was admitted to the intensive care unit, where she was intubated and placed on a mechanical ventilator. The low-income setting was a major barrier in obtaining intravenous immunoglobulin until the patient died. Our study aims to present an MG case with features of MG exacerbation following administration of a second dose of AZD1222. Conclusion: Little is known about the effect of different COVID-19 vaccines on subgroups of patients with autoimmune diseases like MG. In our case, an exacerbation of MG may have been precipitated by the COVID-19 AstraZeneca vaccine. Therefore, more efforts and experimental studies may be needed, with closer vigilance in MG patients

New Onset of Myasthenia Gravis following COVID-19 Vaccination: A Case Report

Myasthenia gravis (MG) is a rare autoimmune disease and the most common neuromuscular junction disorder. The most common symptoms are diplopia, ptosis, and fluctuating weakness of ocular and limb muscles. Here we report a case of MG after COVID-19 vaccination. A 37-year-old Iranian lady presented with generalized weakness, diplopia, and ptosis after three days from taking the second dose of COVID-19 vaccine. Symptoms began three days after taking the second dose of Sinopharm BIBP COVID-19 vaccine (BBIBP-CorV) and worsened within a week. Her past medical history included migraine-type headaches and gastric reflux. She was consuming Rizatriptan and Nortriptyline for her migraine headache and Pantoprazole, Domperidone, and Sertraline for stomach reflux. She had a family history of Essential tremor in her father, uncle, and grandfather. Antibody against the acetylcholine receptor (AChR-Ab) was more than eight times compared to the normal range. The pattern of repetitive nerve stimulation was suggestive for MG. Treatment with corticosteroid, azathioprine, and pyridostigmin led to amelioration of symptoms. Follow-up testing revealed AChR-Ab returned to the normal range. There are some case reports in that a chronic autoimmune disorder flared up after the COVID1-9 infection or its vaccination. There are several reports of MG exacerbations, acute respiratory distress syndrome, higher ICU admission, and mortality rate and worsening neurological symptoms after COVID-19 infection. There is still debate about the association between neuromuscular disorders and COVID-19 infection and vaccination. This matter is more doubtful for myasthenia gravis.

Myasthenia Gravis Exacerbation Following COVID-19 Vaccine: A Case Report

Background: As of December 2021, the World Health Organization (WHO) reports that Coronavirus disease 2019 (COVID-19) led to about 5,403,662 deaths. While COVID-19 has resulted in millions of deaths worldwide to date, vaccination remains the mainstay of infection control. AZD1222 (AstraZeneca vaccine) was distributed in Sudan by the COVID-19 Vaccines Global Access facility in March 2021. It was added to the emergency use list by WHO in the middle of February 2021. However, vaccine safety among patients with autoimmune diseases, such as myasthenia gravis (MG), is yet to be established. MG is a relatively rare illness that could result in life-threatening complications. Myasthenic crisis is considered the most serious complication of MG that can lead to death due to aspiration and respiratory failure. Plasma exchange (PLEX), Immunoadsorption (IA), and intravenous Immunoglobulin (IVIG) are the first-line treatment for myasthenic crisis. It is proven that cortisone has a positive effect when used as add-on therapy with PLEX/IA and IVIG.&#x0D; &#x0D; The case: We report the case of a 37-year-old Sudanese female who presented to the emergency room with an exacerbation of her previously well-controlled MG following her second dose of AZD1222 vaccination. The exacerbation symptoms at time of presentation were severe generalized body weakness that increasing overtime and shortness of breath. Computerized tomography of the chest was performed, and it revealed no evidence of COVID-19. Management at the ER started with rehydration and IV methylprednisolone 1g, followed by IV hydrocortisone 200mg. She continued to deteriorate and was admitted to the intensive care unit where she was intubated and placed on a mechanical ventilator. IVIG was requested but couldn't be obtained due to the low-income setting, and fourteen days after admission patient died due to circulatory collapse. Our study aims to present an MG case with features of MG exacerbation following the administration of the second dose of AZD1222.&#x0D; &#x0D; Conclusion: Little is known about the effect of different COVID-19 vaccines on subgroups of patients with autoimmune diseases like MG. Although the safety profile of AZD1222 is generally reassuring, people with severe underlying diseases were excluded from trials. Therefore, more efforts and experimental studies may be needed, with closer vigilance in MG patients. It has not been elucidated how the COVID-19 vaccine might provoke autoimmunity, but several theories have been proposed. Molecular mimicry theory can explain how the genetic material of a virus could provoke autoimmunity, it describes the cross-reactivity of antibodies produced against proteins that are encoded by viral genetic material with the proteins located at the post-synaptic membrane. There is a debate about whether vaccine benefit outweighs the risk in MG patients or not. However, we believed that MG patients should be informed about the benefit and risks of COVID-19 vaccination.&#x0D;

Peripheral nervous system adverse events associated with immune checkpoint inhibitors

BackgroundImmune checkpoint inhibitors (ICIs) represent an effective cancer immunotherapy yet are associated with immune-related adverse events (irAEs). The aim of this study was to characterize irAEs involving the peripheral nervous system (PNS-irAEs) in a real-world cohort of ICI-treated patients.MethodsCancer patients treated with ICIs between January 2014 and March 2022 were included. Patients with PNS-irAEs were identified and divided into two groups: (1) cranial/peripheral neuropathies and (2) myasthenia gravis (MG) and/or myositis. Clinical characteristics and outcomes, measured with the modified Rankin Scale (mRS), were compared among the two groups.ResultsAmong 920 ICI-treated patients, 20 patients (2.17%) developed a PNS-irAEs. The median latency from ICI exposure was 8.8 weeks and the median time from onset to clinical nadir was 3.5 weeks. Eleven patients developed a neuropathy: polyneuropathy (n = 4), cranial neuropathy (n = 3), small-fiber neuropathy (n = 3), brachial plexopathy (n = 1). Nine patients presented MG and/or myositis: concomitant MG and myositis (n = 6), isolated myositis (n = 2), exacerbation of MG (n = 1). Immunosuppressive treatment and/or ICI withdrawal determined a significant clinical improvement, expressed by a mRS reduction, in the neuropathy group (p = 0.004), but not in the MG/myositis group (p = 0.11). Overall, death due to irAEs occurred in four patients (20%), all with MG/myositis. Compared to patients with neuropathies, those with MG/myositis had a shorter latency onset (p = 0.036), developed more frequently concomitant non-neurologic irAEs (p = 0.028) and showed a higher mortality rate (p = 0.026).ConclusionsIn our large cohort of ICI-treated patients, 2.17% developed PNS-irAEs. Compared to ir-neuropathies, ir-MG/myositis tend to occur earlier from ICI exposure and present a worse response to treatment and a higher mortality.

A real-world analysis of factors associated with high healthcare resource utilization and costs in patients with myasthenia gravis receiving second-line treatment

Despite current treatments, patients with myasthenia gravis (MG) experience unpredictable and inadequately controlled symptoms, lending to variability in the clinical and economic burden of disease. However, limited data are available on MG healthcare costs, and specifically, no data on patients initiating second-line therapy. Using claims data from the IBM® MarketScan® database, we assessed patient characteristics, healthcare resource utilization, and costs among MG patients initiating second-line therapy, and identified potential factors associated with high healthcare costs over a two-year follow-up period. We identified 1498 patients, of whom 49% and 31% received chronic steroids and non-steroidal immunosuppressants (NSISTs) as their second-line therapy, respectively. During follow-up, 49% experienced ≥1 MG exacerbation. Among all patients, mean all-cause total healthcare cost was $106,821 per patient during follow-up, with $88,040 and $18,780 attributed to medical and pharmacy costs, respectively. In a multivariable analysis, variables significantly associated with high cost included use of high-dose steroids, chronic intravenous immunoglobulin (IVIg, ≥6 cycles), and 1 and ≥ 4 (but not 2–3) MG exacerbations in the first year after second-line therapy initiation. Any number of exacerbations were associated with high cost in a univariable analysis. A stratified cost analysis showed that patients with >1 exacerbation, ≥1 treatment switch, and high-dose steroid use in this first year experienced $198,487, $114,037, and $79,752 mean MG-related total healthcare spend during follow-up, respectively. These data suggest that patients receiving chronic IVIg or NSISTs for MG experience significant economic burden. Disease characteristics including exacerbation and treatment history may be an indicator of future high costs.

Discussion

Discussion

Impact of the COVID-19 pandemic on patients with myasthenia gravis: A survey of the Myasthenia Gravis Foundation of America MG patient registry.

Factors associated with coronavirus disease 2019 (COVID-19) infection among the myasthenia gravis (MG) population are incompletely understood. This study aimed to characterize the behavior of MG patients during the pandemic and to examine risk factors associated with COVID-19 infection. A "COVID-19 Survey" was sent to MG Patient Registry participants in the summer of 2020 (CSS20) and winter of 2021 (CWS21). Survey results were summarized descriptively. Demographics, disease characteristics, medication use, and survey results were compared between those reporting COVID-19 diagnosis (COVID), COVID-19 like symptoms without diagnosis (COVID-Like), and asymptomatic participants. A total of 454 and 665 participants completed the CSS20 and CWS21 surveys respectively; 326 participants completed both. Most continued follow-up visits and MG treatments. The frequency of COVID-like symptoms was similar between CSS20 and CWS21, while COVID-19 exposure (6% vs. 27%), COVID-19 testing among symptomatic individuals (35% vs. 78%), and COVID-19 diagnosis (0.2% vs. 6%) were higher in the CWS21. Cough, fever, fatigue, myalgia, anosmia/ageusia, and hospital and intensive care unit (ICU) admissions were more frequent in the COVID compared to the COVID-Like group. COVID-19 exposure (odds ratio [OR] 7.88), number of people in the household (OR 1.31), and report of MG exacerbation before the pandemic (OR 2.6) were independently associated with COVID-19 infection. COVID-19 affected MG patients increasingly through the early pandemic. While face-to-face contact with a COVID-19 infected individual was an obvious risk factor, MG patients who had more people in the household and unstable disease were at elevated risk for COVID-19 infection.

Nomogram for the acute exacerbation of acetylcholine receptor antibody-positive generalized myasthenia gravis.

An acute exacerbation of myasthenia gravis (MG) can lead to the life-threatening myasthenia crisis which can increase the in-hospital mortality. This study aimed to clarify the correlative factor of the severity and activity of MG and the predictors of its exacerbation. A prospective study was conducted to compare the clinical characteristics of acetylcholine receptor antibody (AChR-Ab)-positive generalized MG during acute exacerbation (AE) and in a stable state (SS). Logistic regression was used to determine risk factors, and a nomogram was developed. A total of 97 AChR-Ab MG patients were enrolled, of whom 44 had AE and 53 were in SS. The concentrations of AChR-Ab were 35.24 (23.26, 42.52) nmol/L and 19.51 (8.30, 36.93) nmol/L in the AE and SS groups (P = 0.005), respectively. The receiver operating characteristic curve showed that a single AChR-Ab predicted severity and acute exacerbation, with an area under the curve (AUC) of 0.679. Logistic regression analysis showed that, in addition to AChR-Ab (P = 0.018), bulbar symptoms (P = 0.001), interleukin (IL)-6 (P = 0.025), CD4+/CD8+ T cell ratio (P = 0.031), and CD19+ B cell proportion (P = 0.019) were independent risk factors for acute exacerbation of MG. The developed nomogram had an AUC of 0.878. The Hosmer and Lemeshow chi-square test was 4.37 (P = 0.929). AChR-Ab concentration was positively correlated with the severity and activity of MG. AChR-Ab concentration, alongside bulbar symptoms, IL-6 concentration, CD4+/CD8+ T cell ratio, and CD19+ B cell proportion can predict the acute exacerbation of MG.

Risk factors associated with adverse pregnancy outcomes and postpartum exacerbation in women with myasthenia gravis.

Myasthenia gravis (MG), an autoimmune neuromuscular disease affecting women of childbearing age, exerts an impact on pregnancy, and vice versa. The purposes of the study were to evaluate adverse pregnancy outcomes and postpartum exacerbation in a cohort of Asian MG women, and to explore the predictors for these outcomes. Thirty-seven MG pregnancies of 33 women followed in Xiangya and the second Xiangya hospitals between January 2012 and January 2022, were included in this study. Baseline maternal data, maternal complications, and neonatal outcomes were extracted from medical records. MG courses were evaluated during pregnancy and postpartum 1 year. In 5.4% of cases, MG exacerbation was reported during gestation, mostly in the third trimester, and in 38.9% in the postpartum period. Maternal complications were measured in 59.5% of women, gestational diabetes mellitus (GDM) taking the lead (29.7%) followed by premature rupture of membranes (PROMs) (18.9%). Transient neonatal MG (TNMG) and hyperbilirubinemia (HB) were seen in 24.3% of newborns. Body mass index (BMI) was the only independent predictor for maternal obstetric complications (p=.017), while thyroid disorders for GDM (p=.006). Younger mothers tended to give birth to babies with TNMG (p=.015). Primipara was the only risk factor for HB (p=.015). Higher gestational BMI gain (GBG) (p=.049) and without thyroid disorder (p=.017) were independent risk factors for puerperal exacerbation. Activated partial thromboplastin time and thyroid-stimulating hormone levels could be reliable to predict puerperal exacerbation. Most MG patients have unaffected courses during pregnancy but face a higher rate of maternal and fetal complications. Risk factors identified in our study aid the management of pregnancy in MG women.

Developing and validating a nomogram to predict myasthenia gravis exacerbation in patients with postoperative thymoma recurrence.

Myasthenia gravis (MG) is one of the most common accessory syndromes for thymoma patients. To reduce MG exacerbation and guide clinical practice, we developed a nomogram for predicting MG exacerbation in patients with postoperative thymoma recurrence. Retrospective study of 176 patients with recurrence following thymoma resection who were admitted to the People's Hospital of Shijiazhuang's Center of Treatment of Myasthenia Gravis between 2013 and 2021. Among them, 120 patients with recurrent thymoma from 2013 to 2020 were selected as the training cohort, and 56 patients in 2021 as the validation cohort. Univariate and multivariate logical regression was used to determine the risk factors and draw the nomogram, and the parameters in the nomogram were proportionally assigned from 0 to 100 points. Finally, the performance of the model is evaluated by internal inspection and external inspection. Multivariate analysis revealed that postoperative treatment plan and the pathologic classification of the thymoma were independent predictors of MG exacerbation in the training cohort (n=120), so they were used to create the nomogram, which had a well-fit calibration curve and good concordance index of 0.77 [95% confidence interval (CI): 0.69-0.86] for the training cohort and 0.74 (95% CI: 0.58-0.91) for the validation cohort, respectively. Calculations were made to determine the nomogram's sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV). The training cohort were 75.7% (95% CI: 66.1-83.4%), 64.7% (95% CI: 38.6-84.7%), 92.9% (95% CI: 84.5-97.1%) and 30.6% (95% CI: 16.9-48.3%) respectively, while the corresponding validation cohort were 84.1% (95% CI: 69.3-92.8%), 66.7% (95% CI: 35.4-88.7%), 90.2% (95% CI: 75.9-96.8%) and 53.3% (95% CI: 27.4-77.7%) respectively. We identified the risk factors for MG exacerbation in patients with postoperative recurrence of thymoma and drew a nomogram, which can be used to calculate the probability of MG exacerbation and guide clinicians to choose post-operative treatment.

Clinical features and outcomes of patients with myasthenia gravis affected by COVID-19: A single-center study

IntroductionMyasthenia Gravis (MG) is an autoimmune disorder that can exacerbate for various reasons including infections. In this study, we describe clinical symptoms, outcomes, and management of MG patients affected by COVID-19 infection. MethodsThis observational retrospective study was performed on patients previously diagnosed as MG, presenting with COVID-19 in the clinic or emergency department between April 2020 and August 2021. The clinical data, outcome, and therapeutic interventions were assessed in 83 patients with MG and COVID-19 infection. ResultsSeventy-seven patients performed PCR testing for COVID-19, of which 73 (94.8 %) were positive. Seven patients had the positive serologic test for COVID-19 (IgG and IgM). Fifty-seven (68.7 %) patients had lung involvement. Thirty-five (42.1 %) of patients were admitted to the hospital. Twelve (14.5 %) patients needed hospitalization in an intensive care unit (ICU), with a mean stay of 7.36 ± 5.6 days (rang: 2–20 days). Four (4.8 %) patients were intubated and required mechanical ventilation. Sixteen (19.3 %) patients experienced an exacerbation of myasthenia gravis and were treated with PLEX (n = 2), IVIG (n = 7), and intravenous (IV) methylprednisolone (n = 7). The outcome was favorable in 79 patients and fatal in four patients, three of whom had other comorbidities. One patient died due to severe COVID-19 involvement. ConclusionThe findings from our study demonstrated that patients with previous MG concurrence with COVID-19 have favorable clinical outcomes. Most patients did not need to be hospitalized and more than 80 % of patients did not display MG exacerbation.

Myasthenia gravis treated in the neurology intensive care unit: a 14-year single-centre experience.

Severe myasthenia gravis (MG) exacerbation with respiratory failure and/or dysphagia usually requires monitoring and treatment in the neurology intensive care unit (NICU). The aim of our study was to identify all patients with severe MG exacerbation treated in the NICU in order to assessed potential factors affecting patients' need for mechanical ventilation, occurrence of complications and the final outcome. We retrospectively included all patients with severe exacerbation of MG who required management in the NICU during a 14-year period. Baseline sociodemographic and clinical features, data on medication, comorbidities and outcome were obtained by reviewing medical records and institutional databases. Our study comprised 130 severe MG exacerbations detected in 118 patients. Median age of patients was 61.5years, and women accounted for 58.5% of the patients. Half of the patients required mechanical ventilation during hospitalization. Lethal outcome was observed in 12.3% of severe MG exacerbations. Only elder age was an independent negative predictor of survival (OR 0.89, 95% CI 0.82-0.97, p < 0.01). Complications during hospitalization were detected in 50% of patients. A higher number of comorbidities (OR 1.09, 95% CI 1.60-2.35, p = 0.01) and mechanical ventilation (OR 28.48, 95% CI 8.56-94.81, p < 0.01) were independent predictors of complications during hospitalization. Patients with a severe MG exacerbation who do not require mechanical ventilation have a good outcome after treatment in the NICU. Elder age is an independent predictor of lethal outcome in patients with severe MG exacerbation. Mechanical ventilation and a higher number of comorbidities lead to more frequent complications.

Rituximab in Myasthenia Gravis- Experience from a Low- and Middle-Income Country (LMIC) Setting.

Myasthenia gravis (MG) is an immune-mediated disorder of the neuromuscular junction. About 10% are refractory to immunosuppressive therapy. To analyze the response of patients with generalized MG to rituximab. A retrospective review of patients with MG who received rituximab was carried out (n = 13, M:F = 6:7, mean age: 44.84 ± 15.73 years). Myasthenia Gravis Foundation of America (MGFA), MGFA post-intervention status (MGFA-PIS), and Myasthenia Gravis Status and Treatment Intensity (MGSTI) were assessed before and after rituximab. The duration of MG was 104.07 ± 92.25 months. Before rituximab, the MGFA was IIA/IIB/IIIA/IIIB/IVB/V in 1/1/2/6/2/1 patients and MGSTI was four in eight patients and six in three patients. The mean duration of follow up was 20.92 ± 14.06 months (range, 4 to 42 months). Dose reduction or discontinuation of cholinesterase inhibitors could be achieved 12 patients. Complete stable remission (CSR) and pharmacologic remission (PR) were achieved in one and four patients respectively and five patients had minimal manifestations. Most patients attained level 0, 1 or 2 MGSTI at last follow up. No rituximab infusion-related adverse events were noted. Three patients had exacerbation of MG between one to five weeks after rituximab administration. Three patients died, one each due to a cardiac event unrelated to MG or treatment, complications related to myasthenic crisis, and coronavirus disease. Rituximab was effective in bringing about remission in MG and can be considered as a first-line agent. However, it has to be administered under close supervision as some patients develop exacerbation of MG akin to steroid-induced worsening.