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.

Cogan's sign in a patient with suspected post-COVID-19 vaccine-associated myasthenia gravis.

The Cogan's sign is indicative of myasthenia gravis. This is the first report of neurological signs in a patient with post-COVID-19 vaccine-associated myasthenia gravis in Brazil. In this case, a previously healthy 68-year-old woman presented with proximal limb weakness, left ptosis, and diplopia 1 month after receiving her fourth dose of the COVID-19 vaccine. Neurological examination revealed the presence of Cogan's sign, and she recovered rapidly after treatment. To our knowledge, this is the first reported case of myasthenia gravis associated with the COVID-19 vaccine in Brazil.

An observational study on the safety of COVID-19 vaccination in patients with myasthenia gravis.

OBJECTIVE: There is concern that the coronavirus disease (COVID-19) vaccine may trigger or worsen autoimmune diseases. The objective of this study was to determine the impacts of COVID-19 vaccination on symptom severity in patients with myasthenia gravis (MG). METHODS: A total of 106 enrolled patients with MG who were vaccinated against COVID-19 were followed up, and a questionnaire was used to document in detail the exacerbation of muscle weakness after vaccination and all other uncomfortable reactions after vaccination. Demographic, clinical characteristics, medication, and vaccination data were collected by follow-up interview. The main observation outcome was whether the MG symptoms of patients were exacerbated. The definition of exacerbation is according to the subjective feeling of the patient or a 2-point increase in daily life myasthenia gravis activity score relative to before vaccination, within 30 days after vaccination. RESULTS: Of 106 enrolled patients [median age (SD) 41.0 years, 38 (35.8%) men, 53 (50.0%) with generalized MG, 74 (69.8%) positive for acetylcholine receptor antibody, and 21 (19.8%) with accompanying thymoma], muscle weakness symptoms were stable in 102 (96.2%) patients before vaccine inoculation. Muscle weakness worsened in 10 (9.4%) people after vaccination, of which 8 patients reported slight symptom worsening that resolved quickly (within a few days). Two (1.9%) of patients showed serious symptom aggravation that required hospitalization. CONCLUSION: Our results suggest that inactivated virus vaccines against COVID-19 may be safe for patients with MG whose condition is stable. Patients with generalized MG may be more likely to develop increased muscle weakness after vaccination.

COVID-19 and autoimmune diseases of the nervous system - an update.

INTRODUCTION: Due to a similar pathomechanism, COVID-19 infection may significantly affect the course of autoimmune diseases (AIDs). In our review, we aimed to assess the severity of SARS-CoV-2 infection, response to treatment, and the impact of COVID-19 infection on the course of the underlying disease in patients with neuroimmune diseases. STATE OF THE ART: In the time of the COVID-19 pandemic, it was important to determine the influence of COVID-19 infection on the course of autoimmune diseases due to the weakened immune system and immunosuppressive therapies. CLINICAL IMPLICATIONS: Many reports have indicated that in patients with AIDs, the existence of the disease is not associated with a worse prognosis in the course of the viral infection. Patients in advanced stages of the disease, elderly patients, and those with comorbidities are at risk of more frequent hospitalisations and higher mortality in the course of COVID-19. Moreover, some drugs used in AIDs have been tested for their efficacy in SARS-CoV-2 infection. Episodes of newly diagnosed myasthenia gravis, Guillain-Barré syndrome, acute disseminated encephalomyelitis (ADEM), and neuromyelitis optica spectrum disorder (NMOSD) secondary to COVID-19 or vaccination have also been reported. Vaccination against this pathogen is highly recommended in most patients with AIDs. FUTURE DIRECTIONS: Despite many studies on the association between COVID-19 and neuroimmune diseases, more specific data is needed. The approach to patients with AIDs should be individual, since many issues remain unresolved despite the long-lasting pandemic.

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.

Clinical course and outcome of Covid-19 in patients with myasthenia gravis.

OBJECTIVES: To analyze the prognosis and outcomes of COVID-19 in patients with MG and to determine factors associated with COVID-19 severity in patients with MG. METHODS: Information concerning COVID-19 occurrence in patients with MG was collected in this single-center observational study. Univariate and multivariate analyses were used to identify factors associated with severe Covid-19. RESULTS: Two hundred seventy-five of the 386 records of MG were included in this study. Eighty-two (29.8%) patients had concurrent COVID-19 . The patients' mean age was 50.3 ± 1.6 years, and the mean duration of MG was 6.7 ± 5.4 years. MG was diagnosed after COVID-19 in five cases. Covid-19 was mild in 45 patients (54.9%), moderate in 23 (28.1%), and severe in 14 (17.07%), while mortality occurred in four of the severe cases (4.9%). Three of the exitus patients were receiving rituximab therapy. Pre-Covid MG Activity of Daily Living (MG-ADL) severity scores were significantly high in severe cases. A history of myasthenic crisis was also higher in severe cases. Similarly, univariate and multivariate analyses revealed an association between severe COVID-19 and myasthenic crisis history and high pre-Covid MG-ADL. The type of MG treatment had no independent effect on COVID-19 severity. CONCLUSION: The vast majority of the MG patients made a good recovery from Covid-19. The risk of severe COVID-19 is high in patients with high MG-ADL severity scores and a history of myasthenic crisis.

Pneumonia in myasthenia gravis: Microbial etiology and clinical management.

Introduction: Patients with myasthenia gravis (MG) are prone to the development of pneumonia due to the long-term immunotherapies they receive and a tendency for aspiration. Pneumonia remains a risk factor for MG worsening and is the most prevalent cause of mortality in MG patients. Classification of the pathogens involved and exploration of the risk factors for mechanical ventilation (MV) could aid in improving clinical outcomes. Methods: Between January 2013 and October 2022, we performed an inpatient database review for MG patients with pneumonia concurrence in a tertiary research center specializing in neuromuscular disorders. The clinical and microbiological characteristics of 116 MG patients with pneumonia were retrospectively analyzed. Results: In our cohort, 90.32% (112/124) of organisms were bacteria and 42.86% (48/112) of pathogenic bacteria were carbapenem-resistant. A high abundance of Epstein-Barr virus (EBV) was detected using next-generation sequencing (NGS) in 12 patients, while cytomegalovirus (CMV) was detected in 8 patients. Non-fermentative Gram-negative bacilli were the most prevalent microorganisms, in which ampicillin, sulfamethoxazole-trimethoprim (SMZ-TMP), piperacillin, cefoperazone, ceftazidime, and cefepime may have an anti-infectious effect. Moreover, peripheral lymphocyte percentage [odds ratio (OR) 0.88, 95% CI 0.75-0.96, p = 0.02] and serum globulin (OR 1.16, 95% CI 1.02-1.35, p = 0.03) were significantly associated with the risk of MV demand. Discussion: Our identification of the microbial etiology of pneumonia in MG patients may provide future perspectives on accurate antibiotic options and enable early interventions when risk factors are present.

[COVID-19-associated damage of the peripheral nervous system]. / COVID-19-assotsiirovannye porazheniya perifericheskoi nervnoi sistemy.

Based on the available literature data, the article discusses the prevalence of various forms of damage of the peripheral nervous system in COVID-19 and in the post-COVID period. Information about the clinical features and the course of individual cranial neuropathies, chronic dysimmune neuropathies, Guillain-Barré syndrome, drug-induced neuropathies, fine fiber neuropathy, myasthenia gravis and polyneuropathy of critical conditions was systemized in the context of coronavirus infection. SARS-CoV-2 can trigger various stages of pathogenesis, including neuroimmune ones, which cause long-term consequences of COVID-19, including those associated with the damage of the peripheral nervous system. Awareness of COVID-19-associated pathological conditions will allow assessment of the possible risks of damage of the peripheral nervous system, recognize them at early stages and develop more effective approaches for treatment.

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.

Manifestation of Ocular Myasthenia Gravis as an Initial Symptom of Coronavirus Disease 2019: A Case Report.

For a while, coronavirus disease-2019 (COVID-19) has been a major global pandemic. It primarily affects the respiratory system but has extrapulmonary manifestations such as gastrointestinal and neurological symptoms. Data on myasthenia gravis (MG), as a complication of COVID-19, are limited. We herein report the manifestation of ocular MG as an initial symptom of COVID-19. In November 2020, a 31-year-old healthy woman was referred to Firoozgar Hospital (Tehran, Iran) with left upper eyelid ptosis and diplopia as well as general weakness, myalgia, fever, and nasal congestion for four days prior to admission. Although the acetylcholine receptor antibody in her serum was negative, increased jitter in several muscles led to the diagnosis of ocular MG. Nasal swab reverse transcription-polymerase chain reaction (RT-PCR) assay tested positive for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. Computed tomography (CT) scan of the chest revealed bilateral ground-glass opacities and some foci of consolidation formation, but the thymus was normal. The patient was successfully treated with remdesivir and dexamethasone. The patient was eventually discharged in good condition and with improved neurological symptoms. A limited number of studies have suggested a possible association between MG and COVID-19. Therefore, further data are required to substantiate the proposed association. Clinicians should be aware of ocular MG during the COVID-19 pandemic to better diagnose and manage patients with SARS-CoV-2 infection.

SARS-CoV-2 vaccination and new-onset myasthenia gravis: A report of 7 cases and review of the literature.

Myasthenia gravis (MG) is an antibody-mediated immune disorder of the neuromuscular junction. SARS-CoV-2 is now recognised as a trigger factor for autoimmune diseases and to cause immune-mediated dysregulation, likely due to molecular mimicry induced by viral antigens. SARS-CoV-2 vaccination, similarly, results in exposure to viral antigen. Here we report 7 cases of new-onset myasthenia gravis in timely association with SARS-CoV-2 vaccination, including the first paediatric case identified to date. We also reviewed the literature for other new-onset MG cases reported within 4 weeks of SARS-CoV-2 vaccination and discuss our findings in the context of altered (auto)immunity following SARS-CoV-2 vaccination and/or infection.

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.

Myasthenia gravis complicating the surgical management of achondroplasia: a case-based update.

BACKGROUND: Achondroplasia is the commonest skeletal dysplasia of autosomal dominant inheritance caused by "gain of function" mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. Foramen magnum compression due to accelerated ossification and spinal canal stenosis secondary to reduced interpedicular distance is a hallmark of achondroplasia, driven by G380R nucleotide pair substitution. In severe cases, limb weakness and neurogenic claudication will require surgical decompression. Rarely, a neurological condition may mimic the compressive spinal dysfunction and therefore, non-surgical causes must also be considered in cases of acute neurological deterioration in children with achondroplasia. Myasthenia gravis (MG) is an autoimmune condition resulting in fatigable muscle weakness. There are no reported cases of myasthenia gravis in achondroplasia in the literature. RESULTS: We report a child with achondroplasia scheduled for decompressive surgery for severe lumbar canal stenosis presenting with neurological claudication and knee weakness. While waiting for surgery during the COVID-19 pandemic, she developed generalized fatigability and severe weakness raising concerns of acute worsening of cord compression. Urgent investigations ruled out spinal cord compression but identified an unexpected concurrent myasthenia gravis with positive antibodies to acetylcholine receptors. The surgical intervention was postponed averting the potential risk of life-threatening anaesthetic complications. She was successfully managed with a combination of pyridostigmine, steroids, azathioprine, and plasma exchange. CONCLUSION: We report the first case of myasthenia gravis in achondroplasia and review implications in the management.

Immune Response and Safety of SARS-CoV-2 mRNA-1273 Vaccine in Patients With Myasthenia Gravis.

BACKGROUND AND OBJECTIVES: Evidence regarding the safety and efficacy of messenger RNA (mRNA) vaccines in patients with myasthenia gravis (MG) after immunosuppressive therapies is scarce. Our aim is to determine whether the mRNA-1273 vaccine is safe and able to induce humoral and cellular responses in patients with MG. METHODS: We performed an observational, longitudinal, prospective study including 100 patients with MG of a referral center for MG in our country, conducted from April 2021 to November 2021 during the vaccination campaign. The mRNA-1273 vaccine was scheduled for all participants. Blood samples were collected before vaccination and 3 months after a second dose. Clinical changes in MG were measured using the MG activities of daily life score at baseline and 1 week after the first and second doses. A surveillance of all symptoms of coronavirus disease 2019 (COVID-19) was conducted throughout the study. Humoral and cellular immune responses after vaccination were assessed using a spike-antibody ELISA and interferon gamma release assay in plasma. The primary outcomes were clinically significant changes in MG symptoms after vaccination, adverse events (AEs), and seroconversion and T-cell immune response rates. RESULTS: Ninety-nine patients completed the full vaccination schedule, and 98 had 2 blood samples taken. A statistically significant worsening of symptoms was identified after the first and second doses of the mRNA-1273 vaccine, but this was not clinically relevant. Mild AEs occurred in 14 patients after the first dose and in 21 patients after the second dose. Eighty-seven patients developed a humoral response and 72 patients showed a T-cell response after vaccination. A combined therapy with prednisone and other immunosuppressive drugs correlated with a lower seroconversion ratio (OR = 5.97, 95% CI 1.46-24.09, p = 0.015) and a lower T-cell response ratio (OR = 2.83, 95% CI 1.13-7.13, p = 0.024). DISCUSSION: Our findings indicate that the mRNA vaccination against COVID-19 is safe in patients with MG and show no negative impact on the disease course. Patients achieved high humoral and cellular immune response levels. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that patients with MG receiving the mRNA-1273 vaccine did not show clinical worsening after vaccination and that most of the patients achieved high cellular or immune response levels.

Vaccines and myasthenia gravis: a comprehensive review and retrospective study of SARS-CoV-2 vaccination in a large cohort of myasthenic patients.

INTRODUCTION: Myasthenia gravis (MG) is an autoimmune disease, for which the risk of exacerbation after vaccines is debated. The aim of this study is to review the available literature concerning safety and efficacy of vaccines in MG. In addition, we also conducted a retrospective research of MG exacerbations and new onset MG after anti-SARS-CoV-2 vaccination in a large cohort of patients. METHODS: A study of the available literature regarding vaccines and MG was carried out through research in the online database "Pubmed". We also retrospectively collected data from 80 MG patients, who were followed at the Treviso Hospital and completed an anti-SARS-CoV-2 vaccination cycle. For each patient, we recorded MG exacerbations between first and second doses and within a window period of 1 day - 6 weeks after the second dose. RESULTS: We found 26 relevant articles about influenza, SARS-CoV-2 and other vaccines. No clear associations between most vaccines and MG exacerbations were found. Moreover, cases of new onset post-vaccine MG are mostly anecdotal, except for Japanese encephalitis virus vaccine. Concerning our cohort, 4/80 (5%) MG patients experienced an exacerbation within the post-vaccine window period. In addition, we report a case of new onset post-vaccine MG. DISCUSSION: Inactivated and subunit vaccines are safe and effective in MG. Although some of them, such as anti-SARS-CoV-2 vaccine, might uncommonly cause MG exacerbations, data from our review suggest that benefits still outweigh by far the potential risks, thus they should be recommended to these patients. Nevertheless, large prospective studies are needed for further investigations.