What Is in the Neuromuscular Junction Literature?

ABSTRACT: This update covers recommendations for myasthenia gravis (MG) in patients with coronavirus 2019 disease as well as reports of the clinical features of patients with MG and coronavirus 2019. Updated advisory committee recommendations for the use of thymectomy in generalized MG are also provided. Other MG topics include lipoprotein receptor-4 and agrin antibody associations, factors influencing conversion of ocular to generalized MG, the use of rituximab for more recent onset disease, immunoglobulins for maintenance therapy, and fatigue and depression.

COVID-19 in patients with myasthenia gravis.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has rapidly become a global pandemic, but little is known about its potential impact on patients with myasthenia gravis (MG). METHODS: We studied the clinical course of COVID-19 in five hospitalized patients with autoimmune MG (four with acetylcholine receptor antibodies, one with muscle-specific tyrosine kinase antibodies) between April 1, 2020-April 30-2020. RESULTS: Two patients required intubation for hypoxemic respiratory failure, whereas one required significant supplemental oxygen. One patient with previously stable MG had myasthenic exacerbation. One patient treated with tocilizumab for COVID-19 was successfully extubated. Two patients were treated for MG with intravenous immunoglobulin without thromboembolic complications. DISCUSSION: Our findings suggest that the clinical course and outcomes in patients with MG and COVID-19 are highly variable. Further large studies are needed to define best practices and determinants of outcomes in this unique population.

Safety of inactivated SARS-CoV-2 vaccines in myasthenia gravis: A survey-based study.

Background: Vaccination remains the most effective measure to prevent SARS-CoV-2 infection and worse outcomes. However, many myasthenia gravis (MG) patients are hesitant to receive vaccine due to fear of worsening. Methods: MG patients were consecutively enrolled in two MG centers in North China. The "worsening" after vaccination was self-reported by MG patients, and severity was measured with a single simple question. The general characteristics and disease status immediately prior to the first dose were compared between the worsening and non-worsening groups. Independent factors associated with worsening were explored with multivariate regression analysis. Results: One hundred and seven patients were included. Eleven patients (10.3%) reported worsening after vaccination, including eight patients with mild or moderate worsening and three patients with severe worsening. Only one of them (0.9%) needed an escalation of immunosuppressive treatments. There were significant differences between the worsening and non-worsening groups in terms of Myasthenia Gravis Foundation of America classes immediately before the first dose and intervals since the last aggravation. Precipitating factors might contribute to the worsening in some patients. Logistic regression revealed that only interval since the last aggravation ≤6 months was associated with worsening after SARS-CoV-2 vaccination (P = 0.01, OR = 8.62, 95% CI: 1.93-38.46). Conclusion: SARS-CoV-2 vaccines (an overwhelming majority were inactivated vaccines) were found safe in milder Chinese MG patients who finished two doses. Worsening after vaccination was more frequently seen in patients who were presumed as potentially unstable (intervals since last aggravation ≤6 months). However, mild worsening did occur in patients who were presumed to be stable. Precipitating factors should still be sought and treated for better outcome.

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

INTRODUCTION: Myasthenia 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. METHODS: This 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. RESULTS: Seventy-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. CONCLUSION: The 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.

What is in the Neuromuscular Junction Literature?

ABSTRACT: This update covers a number of treatment topics starting with Fc receptor inhibitors and the Federal Drug Administration approval of efgartigimod. Some uncertainties regarding the use of corticosteroids are addressed, namely the risk of exacerbation with initiation of treatment and how to taper. The presence and potential importance of antibody overshoot following plasmapheresis is noted and the evolving increase in usefulness of acetylcholine receptor antibodies in diagnosing ocular myasthenia. Several recent series and case reports regarding coronavirus 2019 and myasthenia gravis are reviewed. The topics of myasthenia gravis and pregnancy, and another look at thymectomy in MG are provided. Finally, a couple of case reports on Lambert-Eaton myasthenic syndrome concentrate on the ice pack test and an autoantibody association with paraneoplastic cerebellar degeneration and Lambert-Eaton myasthenic syndrome in the same patient.

TREATMENT OF MYASTHENIA GRAVIS PATIENTS WITH COVID-19: REVIEW OF THE LITERATURE.

Coronavirus disease 2019 (COVID-19), caused by the late 2019 outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causes a respiratory disease which could put myasthenia gravis (MG) patients at a greater risk of developing severe disease course, since infections and some drugs are a well-recognized trigger of symptom exacerbation in MG patients. Out of ten most commonly used past and present drugs used in COVID-19 treatment, two (quinolone derivatives and azithromycin) are known to worsen MG symptoms, whereas another two (tocilizumab and eculizumab) might have positive effect on MG symptoms. Colchicine, remdesivir, lopinavir, ritonavir and favipiravir seem to be safe to use, while data are insufficient for bamlanivimab, although it is also probably safe to use. Considering MG treatment options in patients infected with SARS-CoV-2, acetylcholine esterase inhibitors are generally safe to use with some preliminary studies even demonstrating therapeutic properties in regard to COVID-19. Corticosteroids are in general safe to use, even recommended in specific circumstances, whereas other immunosuppressive medications (mycophenolate mofetil, azathioprine, cyclosporine, methotrexate) are probably safe to use. The only exception is rituximab since the resulting B cell depletion can lead to more severe COVID-19 disease. Concerning plasmapheresis and intravenous immunoglobulins, both can be used in COVID-19 while taking into consideration thromboembolic properties of the former and hemodynamic disturbances of the latter. As current data suggest, all known COVID-19 vaccines are safe to use in MG patients.

Characteristics, treatment, and outcomes of Myasthenia Gravis in COVID-19 patients: A systematic review.

OBJECTIVE: Recent studies suggest that the clinical course and outcomes of patients with coronavirus disease 2019 (COVID-19) and myasthenia gravis (MG) are highly variable. We performed a systematic review of the relevant literature with a key aim to assess the outcomes of invasive ventilation, mortality, and hospital length of stay (HLoS) for patients presenting with MG and COVID-19. METHODS: We searched the PubMed, Scopus, Web of Science, and MedRxiv databases for original articles that reported patients with MG and COVID-19. We included all clinical studies that reported MG in patients with confirmed COVID-19 cases via RT-PCR tests. We collected data on patient background characteristics, symptoms, time between MG and COVID-19 diagnosis, MG and COVID-19 treatments, HLoS, and mortality at last available follow-up. We reported summary statistics as counts and percentages or mean±SD. When necessary, inverse variance weighting was used to aggregate patient-level data and summary statistics. RESULTS: Nineteen studies with 152 patients (mean age 54.4 ± 12.7 years; 79/152 [52.0%] female) were included. Hypertension (62/141, 44.0%) and diabetes (30/141, 21.3%) were the most common comorbidities. The mean time between the diagnosis of MG and COVID-19 was7.0 ± 6.3 years. Diagnosis of COVID-19 was confirmed in all patients via RT-PCR tests. Fever (40/59, 67.8%) and ptosis (9/55, 16.4%) were the most frequent COVID-19 and MG symptoms, respectively. Azithromycin and ceftriaxone were the most common COVID-19 treatments, while prednisone and intravenous immunoglobulin were the most common MG treatments. Invasive ventilation treatment was required for 25/59 (42.4%) of patients. The mean HLoS was 18.2 ± 9.9 days. The mortality rate was 18/152 (11.8%). CONCLUSION: This report provides an overview of the characteristics, treatment, and outcomes of MG in COVID-19 patients. Although COVID-19 may exaggerate the neurological symptoms and worsens the outcome in MG patients, we did not find enough evidence to support this notion. Further studies with larger numbers of patients with MG and COVID-19 are needed to better assess the clinical outcomes in these patients.

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

BACKGROUND: Myasthenia 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. RESULTS: Most 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. DISCUSSION: This 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.

Clinical course and outcome of an outpatient clinic population with myasthenia gravis and COVID-19.

INTRODUCTION/AIMS: Coronavirus disease-2019 (COVID-19) may have a more severe course in patients with myasthenia gravis (MG). We aimed to assess severity of the infection and factors contributing to its severity in a group of MG patients, most of whom were not hospitalized. METHODS: One hundred forty outpatients with MG followed between March 2020 and April 2021 were included in our study. Patients were asked to respond to a brief questionnaire in person, by telemedicine, or through electronic messages. RESULTS: Nineteen patients tested positive for COVID-19 by polymerase chain reaction. Two were asymptomatic. Of the 17 symptomatic patients, 11 had mild symptoms. They either had no treatment or received antivirals, antibiotics, and anticoagulants. Their myasthenia was well-controlled before infection and was unaffected by COVID-19. Three patients with moderate COVID-19 required hospitalization, but not intensive care, and had full recovery. Three other patients, the oldest in the cohort, had severe disease: One patient with a postsurgery myasthenic exacerbation before the infection needed intensive care without intubation, but recovered completely; two morbidly obese patients with comorbidities required intubation and died. Corticosteroids were increased in four of the six moderate/severely affected patients. Immunosuppressive (IS) agents were generally continued. Hydroxychloroquine (HCQ) for COVID-19 was used in one patient. DISCUSSION: Most patients had mild COVID-19 and all but two patients recovered. The design of the study made it possible to capture mild cases. Having well-controlled MG before infection and absence of comorbidities likely affected the course of the infection favorably. IS did not influence the progression.

Advances and ongoing research in the treatment of autoimmune neuromuscular junction disorders.

Myasthenia gravis and Lambert-Eaton myasthenic syndrome are antibody-mediated autoimmune diseases of the neuromuscular junction that usually present with weakness in ocular muscles and in proximal muscles of the limb and trunk. Prognosis regarding muscle strength, functional abilities, quality of life, and survival is generally good. However, some patients do not respond to treatment. Symptomatic drugs, corticosteroids, and steroid-sparing immunosuppressive drugs remain the cornerstone of treatment. In the past few years, new biological agents against complement, the FcRn receptor, or B-cell antigens have been tested in clinical trials. These new therapies extend the possibilities for targeted immunotherapies and promise exciting new options with a relatively rapid mode of action. Challenges in their use might occur, with barriers due to an increase in cost of care and additional considerations in the choice of drugs, and potential consequences of infection and vaccination due to the COVID-19 pandemic.

Predictors of outcome in patients with myasthenic crisis undergoing non-invasive mechanical ventilation: A retrospective 20 year longitudinal cohort study from a single Italian center.

About 20% of patients with myasthenia gravis (MG) may develop myasthenic crisis (MC) requiring ventilation, either invasive (MV) or non-invasive (NIV) and intensive unit care (ICU). NIV failure in patients with MC can occur up to 60% of cases admitted to ICU. Moreover it is not known the outcome of MC receiving NIV. Purpose of this study was to identify predictors of outcome in MC who underwent non-invasive ventilator support outside ICU setting. We enrolled 90 patients, 53 females and 37 males admitted to University Hospital of Modena (Italy) between January 2000 and September 2020. Median age at MC was 65 years. Thirty-four patients (37.8%) required MV. Thymectomy was performed in 45 cases, associated with thymoma in 55%, with hyperplastic thymus in 33%. First-line treatment was plasmaexchange (38.8%) or intravenous immunoglobulins (45.6%). Males exhibited higher risk of MV than females .Patients in MV were treated with plasmaexchange as first-line therapy . Our in-hospital mortality rate was low. Nine patients underwent tracheostomy which was significantly related to male gender. Comorbidities had significant effect on length of ICU .Our study confirms as predictors of prognosis in our patients male gender, older age at onset, infections as trigger, pneumonia.

Myasthenia gravis and telemedicine: a lesson from COVID-19 pandemic.

COVID-19 pandemic has induced an urgent reorganization of the healthcare system to ensure continuity of care for patients affected by chronic neurological diseases including myasthenia gravis (MG). Due to the fluctuating nature of the disease, early detection of disease worsening, adverse events, and possibly life-threatening complications is mandatory. This work analyzes the main unresolved issues in the management of the myasthenic patient, the possibilities offered so far by digital technologies, and proposes an online evaluation protocol based on 4 simple tests to improve MG management. Telemedicine and Digital Technology might help neurologists in the clinical decision-making process of MG management, avoiding unnecessary in presence consultations and allowing a rational use of the time and space reduced by the pandemic.

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

AIM OF THE 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. MATERIALS AND METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Telemedicine visits in myasthenia gravis: Expert guidance and the Myasthenia Gravis Core Exam (MG-CE).

INTRODUCTION/AIMS: Telemedicine may be particularly well-suited for myasthenia gravis (MG) due to the disorder's need for specialized care, its hallmark fluctuating muscle weakness, and the potential for increased risk of virus exposure among patients with MG during the coronavirus disease 2019 (COVID-19) pandemic during in-person clinical visits. A disease-specific telemedicine physical examination to reflect myasthenic weakness does not currently exist. METHODS: This paper outlines step-by-step guidance on the fundamentals of a telemedicine assessment for MG. The Myasthenia Gravis Core Exam (MG-CE) is introduced as a MG-specific, telemedicine, physical examination, which contains eight components (ptosis, diplopia, facial strength, bulbar strength, dysarthria, single breath count, arm strength, and sit to stand) and takes approximately 10 minutes to complete. RESULTS: Pre-visit preparation, remote ascertainment of patient-reported outcome scales and visit documentation are also addressed. DISCUSSION: Additional knowledge gaps in telemedicine specific to MG care are identified for future investigation.

Myasthenia gravis and COVID-19: A case series and comparison with literature.

OBJECTIVE: To describe presenting symptoms, clinical outcomes, and therapeutic management of concurrent Coronavirus disease 2019 (COVID-19) infections in patients with a pre-existing myasthenia gravis (MG). METHODS: We conducted a retrospective study in patients with preexisting MG presenting with concurrent COVID-19 between September 21st and November 4th, 2020 when attending the emergency department or routine neurology consultation at the National Institute Mongi Ben Hamida of Neurology of Tunis, Tunisia. RESULTS: Five patients were identified. The Myasthenia Gravis Foundation of America scores (MGFA) prior to COVID-19 infection were class I in one patient, class II (IIa, IIb) in two patients, and class IIIb in one patient. Four patients had mild to moderate courses of COVID-19 infection. One patient presented a critical infection with acute respiratory disease syndrome (ARDS) requiring mechanical ventilation. Two of them also demonstrated signs of MG exacerbation requiring the use of intravenous immunoglobulin in one case. We maintained immunosuppressant therapy to MG in all our patients. All our patients received Azithromycin (AZM) as a part of specific drug treatment of COVID-19 infection. Outcome was favorable in 4 patients and rapidly fatal evolution was observed in the patient with ADRS. DISCUSSIONS AND CONCLUSION: The results from our study suggest that prior MG activity could partially influence the subsequent clinical outcomes. It emerged also that ongoing long-term immunosuppressive immunotherapy to MG should be maintained during the COVID-19 pandemic and that AZM can be used safely in MG patients and concurrent COVID-19 infection.

Telephone consultation for myasthenia gravis care during the COVID-19 pandemic: Assessment of a novel virtual myasthenia gravis index.

INTRODUCTION/AIMS: The aim of the study was to determine the association between the virtual Myasthenia Gravis Impairment Index (vMGII) with other patient-reported outcomes (PROs) of myasthenia gravis (MG) and its usefulness in telephone consultations with MG patients. METHODS: This was a retrospective case series in which vMGII score along with virtual Single Simple Question (vSSQ), virtual Patient-Acceptable Symptom State PASS (vPASS) response, and patient disease status based on Myathenia Gravis Foundation of America postintervention status were collected during telephone consultation along with the MGII, SSQ, and PASS responses during the preceding in-person clinic visits. RESULTS: In 214 patients, the mean difference of vMGII between the vPASS "Yes" and "No" groups was -14.2 ± 1.4 (95% confidence interval, -16.9 to -11.3; P < .001) with mean vMGII for vPASS "Yes" group being 6.4 ± 7.7 and vPASS "No" being 20.5 ± 11.5. A vMGII of 11.5 or higher predicted vPASS "yes" response with a sensitivity of 78.7% and specificity of 81.4%. A strong negative correlation was found between the vMGII and vSSQ (r = -.667; P < .001). The mean vMGII was 0.48 ± 1.42 for patients in remission, and 9.31 ± 10.93 for improved, 9.32 ± 8.79 for stable, and 22.58 ± 14.04 for worsened groups (P < .001). These associations were the same as those obtained during the preceding in-person clinic visit and the direction of change in MGII scores also indicated change in disease status. DISCUSSION: vMGII is an effective measure to assess an MG patient's disease status in telephone consultations and relates well with other PRO measures. The vMGII remains reliable for assessing MG disease status even with removal of the physical examination component.

Description of 3 patients with myasthenia gravis and COVID-19.

BACKGROUND: The COVID-19 pandemic presents two main concerns for patients with myasthenia gravis (MG); chronic immunosuppression may put them at greater risk, and some proposed treatments for COVID-19 could cause MG exacerbation. CASE DESCRIPTION: We present three patients with generalized seropositive MG who developed COVID-19. All patients had a favorable outcome, with only one patient experiencing exacerbation. In this case, exacerbation began before COVID-19; she required ICU admission, non-invasive ventilatory support, and received hydroxychloroquine, lopinavir and ritonavir which were well tolerated. One patient received IVIG in place of scheduled plasma exchange. CONCLUSION: Outcome was favorable in all cases despite immunosuppressive therapy, use of experimental COVID-19 medication and switching of plasma exchange for IVIG.