Myasthenia Gravis Exacerbation Research Articles

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.

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.

Are There Racial Differences in Inpatient Outcomes and Treatment Utilization following Hospitalization for Myasthenia Gravis Exacerbation?

Introduction: Little is known about racial differences in inpatient outcomes following hospitalizations for myasthenia gravis (MG). In this study, we used a claims-based database to assess racial differences in outcomes in hospitalized myasthenics. Methods: The 2006–2014 National Inpatient Sample database was queried using the International Classification of Diseases 9th Edition diagnosis code (358.01) to identify adult patients (age >17 years) undergoing hospitalization for MG. Race was categorized into – white, black/African American (AA), Asian or Pacific Islander, Hispanic, Native American, and other. Complications assessed included urinary tract infections, acute renal failure, cardiac complications, systemic infection, deep venous thrombosis, and pulmonary embolism. Multivariate logistic regression analyses were used to assess whether race was associated with a difference in outcomes, after controlling for baseline demographics, hospital characteristics, and treatment factors. Results: A total of 56,189 patient admissions, using a weighted sample, underwent hospitalization for MG between 2006 and 2014. Black/AA patients had significantly higher odds of experiencing systemic infections (odds ratio [OR] 1.35 [95% confidence intervals [CI] 1.16–1.58]; p < 0.001), deep venous thrombosis (OR 2.11 [95% CI 1.36–3.27]; p = 0.001), and renal failure (OR 1.19 [95% CI 1.05–1.35]; p = 0.005). Black/AA patients were more likely to be intubated (OR 1.09 [95% CI 1.01–1.19]; p = 0.028) and receive noninvasive mechanical ventilation (OR 1.62 [95% CI 1.46–1.79]; p < 0.001), however, were less likely to receive intravenous immunoglobulin (OR 0.77 [95% CI 0.73–0.82]; p < 0.001) and plasmapheresis (OR 0.77 [95% CI 0.72–0.82]; p < 0.001). Black/AA and Hispanic patients had lower mortality (OR 0.74 [95% CI 0.59–0.94; p = 0.012]. Conclusions: Significant racial differences exist in both treatment utilization and inpatient outcomes for patients hospitalized for MG.

Effects of Plasma Exchange Combined with Immunoglobulin Therapy on Consciousness, Immune Function, and Prognosis in Patients with Myasthenia Gravis Crisis: A Prospective Randomized Test

Background Myasthenia gravis (MG) is an acquired autoimmune disease. The main clinical features of MG are skeletal muscle fatigue and pathological fatigue, which worsen at night or after fatigue, such as dyspnea, dysphagia, and systemic weakness. Plasma exchange (PE) is often used in patients with acute exacerbation of MG. Intravenous immunoglobulin (IVIG) is a collection of immunoglobulins from thousands of donors. IVIG can replace a variety of immunosuppressants or PE. However, the effect of PE or IVIG on patients' consciousness, immune function, and prognosis is not clear. Objective A prospective randomized test of the effects of PE combined with immunoglobulin on consciousness, immune function, and prognosis in patients with myasthenia gravis crisis (MGC). Methods Sixty patients with MGC treated from February 2019 to April 2021 were enrolled in our hospital. The cases who received PE were set as the PE group, and those who received PE combined with immunoglobulin were set as the PE+immunoglobulin group. The efficacy, clinical score, state of consciousness, immune function, acetylcholine receptor antibody (AChR-Ab), lymphocyte (LYM), albumin (ALB) levels, and the incidence of adverse reactions were compared. Results The improvement rate was 100.005% in the treatment group and 83.33% in the PE group. After treatment, the clinical score of the PE+immunoglobulin group was lower than that of the PE group, and the clinical relative score of the PE+immunoglobulin group was higher than that of the PE group (P < 0.05). The number of conscious people in the PE+immunoglobulin group was more than that in the PE group (P < 0.05). Immunoglobulin A, immunoglobulin M, immunoglobulin G, and immunoglobulin G in the PE+immunoglobulin group were higher than those in the PE group (P < 0.05). The levels of AChR-Ab and ALB in the PE+immunoglobulin group were higher than those in the PE group, while the level of LYM in the PE+immunoglobulin group was lower than that in the PE group. The incidence of skin system, gastrointestinal system, nervous system, and systemic damage in the PE+immunoglobulin group was lower than that in the PE group (P < 0.05). Conclusion The treatment of MGC with PE combined with immunoglobulin can not only effectively enhance the consciousness and immune function of patients but also effectively promote the prognosis, and the safety of treatment can be guaranteed.

Academic and Employment Status in Patients With Generalized Myasthenia Gravis Treated With Eculizumab: A Case Series.

Objectives:To evaluate the impact of treatment with eculizumab, a terminal complement inhibitor, on academic and employment status in patients with refractory generalized myasthenia gravis (MG).Methods:Case review of 7 US patients.Results:Six patients were aged ≤65 years; one was a full-time student and the remainder were in employment before MG diagnosis. After diagnosis, all patients gave up work (n = 3) or reduced their study/working hours (n = 4). In the 12 months after eculizumab initiation, patients who had stopped work resumed working in some capacity, whereas those who had changed their work/study hours returned to their original work/study pattern. Patients also experienced a reduction in the number of MG exacerbations, and a clinically significant improvement in MG–Activities of Daily Living scores, and were able to reduce other MG medications.Conclusions:These results suggest that treatment with eculizumab may help maintain education/employment activity in patients with refractory generalized MG.

A retrospective longitudinal cohort study of the clinical burden in myasthenia gravis

BackgroundPatients with generalized myasthenia gravis (MG) often experience debilitating exacerbations, with the possibility of life-threatening respiratory crises requiring hospitalization. Long-term longitudinal studies are needed to understand the burden of MG, including in patients whose disease is refractory to conventional treatment.MethodsA retrospective, longitudinal, cohort study was conducted of patients in England aged ≥ 18 years with treatment-refractory or non-refractory MG, using data recorded during 1997–2016 in the Clinical Practice Research Datalink and the Hospital Episode Statistics databases. A control cohort of patients without MG, matched to the patients in the treatment-refractory MG cohort, was also identified. Outcome measures included myasthenic crises, MG exacerbations, MG-related hospitalizations, comorbidities, and all-cause mortality. Descriptive statistics were calculated for the overall MG population. For continuous variables, between-cohort comparisons were made using t tests for normally distributed data and Mann–Whitney U tests for non-normally distributed data. For categorical data, the comparisons were made by chi-squared tests. Differences in clinical outcomes between cohorts were modeled using negative binomial regression.ResultsA total of 1149 patients with MG were included. Overall, 18.4% of patients experienced myasthenic crises, 24.6% experienced exacerbations, and 38.6% underwent MG-related hospitalizations. Most of these events occurred within 2–3 years of diagnosis. Patients with MG refractory to conventional treatment (n = 66) experienced more exacerbations and MG-related hospitalizations than patients with non-refractory disease (n = 1083). Patients with refractory MG experienced a higher frequency of renal disease and hypertension compared with patients with non-refractory MG, and with matched patients without MG. They were also more likely to have diabetes and congestive heart failure than the matched controls. Rates of all-cause mortality during the follow-up period did not differ between patients with refractory MG and non-refractory MG.ConclusionsThese results show that conventional treatments for MG are not adequately managing patients’ symptoms and that patients with refractory MG are more likely to experience certain comorbidities than those with non-refractory MG or matched controls without MG. Future research should focus on the impact of newer targeted therapies on long-term clinical outcomes and comorbid conditions.

Refractory Myasthenia Gravis Exacerbation associated with Marginal Zone Lymphoma (P7-13.009)

Refractory Myasthenia Gravis Exacerbation associated with Marginal Zone Lymphoma (P7-13.009)

Robotic-assisted minimally invasive thymectomy for myasthenia gravis with thymoma.

Robotic-assisted minimally invasive thymectomy for myasthenia gravis with thymoma.

COVID-19 pandemic year in a sample of Polish myasthenia gravis patients: an observational study.

Coronavirus disease 2019 (COVID-19) incidence, mortality, recovery and hospitalisation rates vary in different countries. This study aimed to present the clinical characteristics of a sample of unvaccinated Polish myasthenia gravis (MG) patients during the first year of the COVID-19 pandemic, taking into account the number of MG exacerbations, a detailed description of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection course, and the need to modify immunosuppressive therapies. Clinical rationale for the study: To assess the impact of the first COVID-19 pandemic year on MG course in a sample of unvaccinated patients. A retrospective observational study involving 30 unvaccinated Polish MG patients consulted in a neurological outpatient clinic on 11-31 March, 2020 (baseline) and 11-31 March, 2021 (endpoint). During the period of evaluation, exacerbation of MG requiring hospitalisation was reported in 11 patients. Among them, four were treated with intravenous immunoglobulin and another six required plasma exchange. In the study group, COVID-19 was identified in 10 patients. Of them, seven experienced a mild course of SARSCoV-2 infection with spontaneous recovery. In the remaining three patients, both MG exacerbation and SARS-CoV-2 infection were reported. These patients experienced MG exacerbation in the preceding month or concurrently with COVID-19 and were aged over 50 years. Due to the SARS-CoV-2 infection, they required antibiotic and oxygen therapy, and hospitalisation was necessary in the case of two obese patients. None of the patients died due to COVID-19, and nor did any require discontinuation of immunosuppressive therapies during the study period. In total, 12 patients in the study group experienced neither MG exacerbation nor SARS-CoV-2 infection. In the presented sample of Polish MG patients, favourable outcomes of COVID-19 were observed. Further studies are needed to evaluate the reliable course of COVID-19 taking into account international differences, the types of treatment applied, and the ratio of vaccinated to unvaccinated MG patients.

Myasthenia gravis exacerbation and myasthenic crisis associated with COVID-19: case series and literature review.

BackgroundMyasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction that can be exacerbated by many viral infections, including COVID-19. The management of MG exacerbations is challenging in this scenario. We report 8 cases of MG exacerbation or myasthenic crisis associated with COVID-19 and discuss prognosis and treatment based on a literature review.ResultsMost patients were female (7/8), with an average age of 47.1 years. Treatment was immunoglobulin (IVIG) in 3 patients, plasma exchange (PLEX) in 2 patients, and adjustment of baseline drugs in 3. In-hospital mortality was 25% and 37.5% in 2-month follow-up.DiscussionThis is the largest case series of MG exacerbation or myasthenic crisis due to COVID-19 to this date. Mortality was considerably higher than in myasthenic crisis of other etiologies. Previous treatment for MG or acute exacerbation treatment did not seem to interfere with prognosis, although sample size was too small to draw definitive conclusions. Further studies are needed to understand the safety and effectiveness of interventions in this setting, particularly of PLEX, IVIG, rituximab, and tocilizumab.

Myasthenia gravis in pregnancy: Systematic review and case series.

BackgroundMyasthenia gravis is an autoimmune disease which can impact pregnancy.MethodsSix databases were systematically searched for studies with at least five subjects reporting pregnancy outcomes for women with myasthenia gravis in pregnancy. Assessment of bias was performed for all included studies. Forty-eight cases from our own centre were also included in the analysis.ResultsIn total, 32 publications met inclusion criteria for systematic review, for a total of 33 unique data sets including 48 cases from our institution. Outcome data was available for 824 pregnancies. Spontaneous vaginal delivery occurred in 56.3% of pregnancies. Overall risk of myasthenia gravis exacerbation was 33.8% with a 6.4% risk of myasthenic crisis in pregnancy and 8.2% postpartum. The incidence risk of transient neonatal myasthenia gravis was 13.0%.ConclusionsThe current systematic review provides the best estimates of risk currently available to aid in counselling women with myasthenia gravis in pregnancy.

Methotrexate Use in Generalized Autoimmune Myasthenia Gravis: A Case series

Methotrexate (MTX) is an inexpensive and well-tolerated immunosuppressive medication that is used anecdotally in autoimmune myasthenia gravis (MG). However, the efficacy in MG is unclear at this time. This retrospective analysis describes six patients with acetylcholine receptor antibody positive MG who were treated with MTX and corticosteroids. The efficacy of MTX was measured by steroid-sparing effect and the Myasthenia Gravis Foundation of America (MGFA) classification. MTX initiation was associated with a reduction in prednisone dosage in all patients. Minimal manifestation status was reached at an average duration of 10 months in 5 patients. No patients were hospitalized for myasthenia gravis exacerbations. There were no major side effects experienced with MTX use. This retrospective analysis suggests that MTX is safe and probably efficacious as a corticosteroid-sparing agent in the management of MG.

154 Transient left ventricular systolic dysfunction during intravenous immunoglobulins treatment for myasthenia gravis exacerbation

Abstract A 61-year-old man suffering from myasthenia gravis with predominant bulbar involvement since 10 months before admission, was diagnosed with thymoma in April 2021. He had no relevant comorbidities except for history of polymorphic ventricular ectopic beats. In this regard, in 2019 he had undergone transthoracic echocardiogram and coronary computed tomography angiography, which resulted both normal. After 1 month, due to poor response to standard medical therapy with prednisone and pyridostigmine and in preparation for thymectomy, an intravenous immunoglobulins (IVIG) treatment was prescribed leading to mild clinical improvement (Myasthenia Gravis Foundation of America Clinical Classification IIIA—MGFA). Two weeks later, the patient underwent robotic-assisted thoracoscopic thymectomy without complications. Pathological findings were consistent with type B1 Thymoma classified as Masaoka Stage IIB (TNM Stage pT1a). After discharge the patient complained a rapid worsening of neurological symptoms (MGFA IIIB) leading to an urgent hospitalization for Myasthenia Gravis exacerbation in the middle of June. On admission Intravenous Immunoglobulins (IVIG) treatment was immediately started. After administration of the second IVIG dose, he had a myasthenic crisis complicated by refractory heart failure with significant increase of cardiac troponin up to 5.768 ng/L, requiring invasive ventilation, inotropic support and urgent transfer to the Cardiac Intensive Care Unit (CICU). The 2D echo showed severe left ventricular systolic dysfunction (LVEF 20%) with diffuse hypokinesis. The patient underwent cardiac catheterization and coronary angiography that confirmed severe reduction of the LVEF (LVEF 23%) with embolic occlusion of the distal posterior descending coronary artery (PDA) without other significant coronary artery stenosis. An endomyocardial biopsy was performed, which revealed cardiomyocytes of normal dimensions with sporadic cytoplasmic vacuolization and excluded signs of inflammation, fibrosis, necrosis and viral myocarditis. The day after the patient completed IVIG treatment. During the following days, despite persistence of severe left ventricular systolic dysfunction, he was successfully weaned form inotropic and ventilatory support. At neurological evaluation he reported persistence of severe bulbar involvement with upper and lower limbs weakness. Five days later, the patient had a sudden cardiac arrest for pulseless electrical activity. Advanced cardiac life support requiring inotropes and invasive ventilation was performed for 28 min before returning to spontaneous circulation. The echocardiogram excluded pulmonary embolism and mechanical complications but showed severe left ventricular systolic dysfunction. A new coronary angiography showed clear coronary arteries including PDA. Because of severe haemodynamic compromise, an Impella CP device was implanted and set at maximum support level (P8 flow, &amp;gt;3 L/min). A neurological exam revealed no severe neurological sequelae. As a result of the long CPR the patient had a massive left haemothorax, initially treated with multiple blood transfusions and pleural drainage. Two days later, due to persistence of haemodynamic instability and active pleural bleeding with incessant severe anaemia the case underwent a Heart Team discussion where it was decided to escalate Impella CP device to Veno-Arterial Extracorporeal Membrane Oxygenation (VA-ECMO) and then perform a video-assisted thoracoscopic evacuation of the haemothorax. Both procedures were carried out without complications. The patient had an immediate haemodynamic improvement which led to rapid weaning from inotropic support. Haemoglobin was stable. The 2D echo showed significant improvement of the LVEF (40%). After 3 days, given the persistence of haemodynamic stability, ECMO device was removed and invasive ventilation stopped shortly afterwards. Eleven days later, another 2D echo demonstrated complete recovery of left ventricular systolic function (LVEF 59%). Notwithstanding, the patient reported a progressive worsening of neurological symptoms with generalized myasthenia and severe bulbar involvement (MGFA IVB) along with episodes of respiratory muscle fatigue requiring non-invasive ventilation. For this reason, the patient was transferred to Subintensive Respiratory Unit and the case underwent a new multidisciplinary discussion involving neurologists, cardiologists and haematologists. Specialists agreed upon potential causal role of IVIG treatment in transient left ventricular dysfunction and considered re-administration absolutely contraindicated. Thus, they prescribed five plasmapheresis treatments and up-titration of corticosteroid therapy (methylprednisolone up to 60 mg od). An immediate and outstanding improvement of neurological symptoms was obtained (MGFA IIIA) and the patient was discharged from hospital 1 week later.

AB011. Rescue chemotherapy in a patient with thymoma and severe symptoms of myasthenia gravis: a case report

: Thymomas often co-exist with myasthenia gravis (MG). The exacerbation of MG can be related to the thymoma progression, surgery or chemotherapy. We are presenting a case of a thymoma patient effectively treated with a rescue chemotherapy due to aggravated symptoms of MG. The 50-year-old female presented the symptoms of MG. Radiologically thymic tumor was detected and the patient underwent video thoracoscopic thymectomy. Type B2, Masaoka-Koga stage II thymoma, pR0 was diagnosed. The patient did not approve adjuvant radiotherapy. Neurological symptoms were controlled by pyridostigmine for 15 months, then exacerbated—speech impairment, dysphagia, muscular fatigue and shortness of breath occurred. CT scan revealed a pleural dissemination of the thymoma. Despite immunoglobulin and prednisone therapy, respiratory failure progressed, and the patient required mechanical ventilation and plasmapheresis. Temporary clinical improvement was achieved. Then the patient again required mechanical ventilation, plasmaphereses, higher doses of pyridostigmine and prednisone. The symptoms diminished, but the patient performance status was moderate (ECOG 3), still presented bulbar symptoms and needed a home-care respirator and enteral nutrition (PEG). An X-ray scan revealed the regression of tumors (an effect of the prednisone treatment). The patient was qualified to rescue chemotherapy: cisplatin-etoposide. Stabilization of the disease was achieved (RECIST 1.1) with significant improvement of neurological condition. Three weeks later the patient could cease using the respirator and started to eat blended meals. After 3 courses of chemotherapy, the patient underwent re-thoracotomy and multiple pleural and mediastinal tumors were removed. The tumors revealed combined morphology of type B3B2 thymoma. No aggravation of MG symptoms was observed in the perioperative period. Within the next 4 years of follow-up the thymoma relapsed 3 times and all episodes were accompanied by severe myasthenic crises with respiratory failure requiring periodic ventilation. The recurrences were treated surgically and by two lines of palliative chemotherapy: paclitaxel/carboplatin, doxorubicin/cyclophosphamide. Currently, the patient is in good condition, ECOG 1. The regression of the tumor achieved due to high doses of prednisone and chemotherapy led to significant clinical improvement of neurological symptoms. Patients with thymomas accompanied by MG need multidisciplinary care and close collaboration of surgeons, oncologists, neurologists and anesthesiologists.

Update on Intravenous Immunoglobulin in Neurology: Modulating Neuro-autoimmunity, Evolving Factors on Efficacy and Dosing and Challenges on Stopping Chronic IVIg Therapy

In the last 25 years, intravenous immunoglobulin (IVIg) has had a major impact in the successful treatment of previously untreatable or poorly controlled autoimmune neurological disorders. Derived from thousands of healthy donors, IVIg contains IgG1 isotypes of idiotypic antibodies that have the potential to bind pathogenic autoantibodies or cross-react with various antigenic peptides, including proteins conserved among the “common cold”-pre-pandemic coronaviruses; as a result, after IVIg infusions, some of the patients’ sera may transiently become positive for various neuronal antibodies, even for anti-SARS-CoV-2, necessitating caution in separating antibodies derived from the infused IVIg or acquired humoral immunity. IVIg exerts multiple effects on the immunoregulatory network by variably affecting autoantibodies, complement activation, FcRn saturation, FcγRIIb receptors, cytokines, and inflammatory mediators. Based on randomized controlled trials, IVIg is approved for the treatment of GBS, CIDP, MMN and dermatomyositis; has been effective in, myasthenia gravis exacerbations, and stiff-person syndrome; and exhibits convincing efficacy in autoimmune epilepsy, neuromyelitis, and autoimmune encephalitis. Recent evidence suggests that polymorphisms in the genes encoding FcRn and FcγRIIB may influence the catabolism of infused IgG or its anti-inflammatory effects, impacting on individualized dosing or efficacy. For chronic maintenance therapy, IVIg and subcutaneous IgG are effective in controlled studies only in CIDP and MMN preventing relapses and axonal loss up to 48 weeks; in practice, however, IVIg is continuously used for years in all the aforementioned neurological conditions, like is a “forever necessary therapy” for maintaining stability, generating challenges on when and how to stop it. Because about 35-40% of patients on chronic therapy do not exhibit objective neurological signs of worsening after stopping IVIg but express subjective symptoms of fatigue, pains, spasms, or a feeling of generalized weakness, a conditioning effect combined with fear that discontinuing chronic therapy may destabilize a multi-year stability status is likely. The dilemmas of continuing chronic therapy, the importance of adjusting dosing and scheduling or periodically stopping IVIg to objectively assess necessity, and concerns in accurately interpreting IVIg-dependency are discussed. Finally, the merit of subcutaneous IgG, the ineffectiveness of IVIg in IgG4-neurological autoimmunities, and genetic factors affecting IVIg dosing and efficacy are addressed.

Precision Intravenous Immunoglobulin Dosing and Clinical Outcomes: A Retrospective Chart Review.

Intravenous immunoglobulin (IVIg) is used for treatment of acute neurologic conditions such as Guillain-Barre syndrome, chronic inflammatory demyelinating polyradiculoneuropathy relapse, and myasthenia gravis exacerbation. Precision dosing (adjusted or ideal body weight) is proposed to conserve IVIg. There have been no published studies comparing clinical outcomes in traditional dosing (actual body weight) with precision dosing. In 2014, our institution began dosing patients with precision dosing. This decision was largely performed by administration rather than physicians' preference. We sought to analyze our retrospective data to understand the change in dosing methods with neurologic outcomes. We performed a retrospective review of all patients hospitalized at a single center who received IVIg for myasthenia gravis, Guillain-Barre syndrome, and chronic inflammatory demyelinating polyradiculoneuropathy from January 2010 to October 2017. We collected baseline information and clinical outcomes including mortality, readmission, need for second rescue treatment, length of stay, discharge disposition, treatment-related adverse events, and modified research council posttreatment sum score. Length of stay was significantly shorter with precision dosing. There was no statistically significant difference in discharge disposition, readmission, rescue treatment, or modified research council posttreatment sum score with precision dosing. Precision dosing did not adversely affect short-term neurologic outcomes.

COVID-19 in patients with myasthenia gravis

Various infections can frequently lead to the exacerbation of myasthenia gravis (MG). COVID19 infection characterized by lung impairment with respiration failure, massive inflammatory reaction and high mortality may lead to worsening of many neuromuscular disorders including MG. Published series of patients with MG and COVID-19 are considerably variable and differ in disease severity and selected therapeutic approach. In our group of 11 MG patients, substantial worsening was present in 3 patients, and in 4 there was a mild worsening of clinical myasthenic symptoms. In 3 patients, we used high doses of methylprednisolone intravenously, in 2 patients, the oral doses of prednisone were increased to 40 mg/60 mg a day, 1 patient was treated with intravenous immunoglobulin (2 g/kg), and 1 was treated with remdesivir. An 88-year-old woman was diagnosed with MG after COVID-19 infection. A 77-year-old man died after 6 days of mechanical ventilation. COVID-19 infection leads to an exacerbation of clinical symptoms in a large proportion of MG patients with ventilation disorder due to increased muscle fatigue and inflammatory changes in the lung parenchyma.

P-PN019. Pneumonia in a pregnant woman with excacerbated myasthenia gravis

Introduction . Myasthenia gravis (MG) occurs in 10-20 persons per 1 million people per year and in women twice as much as men. Pitfalls in MG therapy include numerous drugs and conditions that could worsen muscle weakness, leading to myasthenic crisis. One of the most common exacerbating conditions is infection, especially pneumonia. This case report will discuss the management of exacerbated MG with pneumonia in a pregnant woman. Results . Mrs. I, 35 years old and 12 weeks pregnant, visited Emergency Room of Dr. Iskak General Hospital with the chief complaint of shortness of breath for two days. There were fever, productive cough, and nausea. A week prior, she forgot to take her pyridostigmine. There was history of dyspnea in her first pregnancy. Her vital signs showed tachypnea and fever, peripheral saturation was normal, and patient was fully alert. There was neither weakness in extremities nor difficulty in swallowing. Remarkable laboratory results were leucocytosis and neutrophilia. She was diagnosed as pneumonia and exacerbated MG. Treatments during hospitalization included cefadroxil 2x500 mg, pyridostigmine 6x60 mg, paracetamol 3x500 mg, O2 nasal cannule 3 L/m, Ventolin nebulization, and ambroxol 3x30 mg. Conclusion . Mrs. I’s clinical features pointed towards pneumonia, but MG exacerbation cannot be fully excluded since pneumonia can worsen the muscle weakness. Therefore, the main purposes of treatment should be to eradicate the bacteria and prevent MG from worsening to myasthenic crisis. Cefadroxil was chosen since it is not teratogenic and does not induce myasthenic crisis. Pyridostigmine was given twice the normal dose, which was in the safe range for not causing microcephaly. In short, dyspnea in a MG patient should be assessed like any other dyspnea case with several differential diagnoses instead of focusing to the MG itself. Treatment of this patient should consider the teratogenic effect to the pregnancy and the exacerbating effect to the MG.

Risk factors for potential drug–drug interactions in patients with myasthenia gravis

ABSTRACT Objectives: Our aim was to determine risk factors for and frequency of potential drug-drug interactions (pDDIs) among hospitalized patients with myasthenia gravis (MG). Methods: This was a retrospective cross-sectional study of the-first time hospitalized MG patients or patients hospitalized because of the exacerbation of MG at the Neurology Clinic of the Clinical Center of Serbia, Belgrade. Medical records and discharge summaries of hospitalized MG patients over a 10-year period were reviewed. The pDDIs were identified by means of Micromedex, and multivariate regression methods were used to reveal potential predictors of number of pDDIs per patient. Results: The study included 687 patients with MG. In total, 2041 pDDIs were detected in 608 (88.5%) patients. Among the discovered pDDIs, 329 different pDDIs were observed. The most frequent pDDIs were pyridostigmine-prednisone (487patients/70.9%) and aspirin-prednisone (90 patients/13.1%) classified as moderate, and enalapril-potassium chloride (71patients/10.3%) classified as major pDDI. Five drugs (aspirin, insulin, prednisone, cyclosporine, metformin) were responsible for 22.6% of different pDDIs. Dyspnea, generalized form of MG, diabetes mellitus, hypertension, total number of drugs-used, use of antiplatelets were identified as the relevant risk factors for total number of pDDIs (R2 = 0.626,F = 73.797, p < 0.001), while age of patients and history of cancer were inversely correlated with such an outcome. Conclusion: The frequency of the pDDIs in hospitalized MG patients is high, and adversely influenced by dyspnea, generalized MG, diabetes mellitus, hypertension, total number of drugs-used and use of antiplatelets.