New-onset Myasthenia Gravis after SARS-CoV-2 infection: case report and literature review.

We report the case of a 19-year-old female patient who developed Myasthenia Gravis 13 days after SARS-CoV-2 infection with positive RT-PCR testing. Her symptoms initially involved the oculo-bulbar district, but they gradually worsened in 3 months converting into a generalized form of Myasthenia Gravis complicated with a myasthenic crisis. A high level of anti-acetylcholine receptor antibodies was found in the serum, while anti-MuSK antibodies were negative; Repetitive Nerve Stimulation and Single-fiber Electromyography were suggestive of Myasthenia Gravis. Intravenous immunoglobulin courses and specific therapy were able to improve her symptoms, but thymic resection was needed to control the disease. This is a report of new-onset Myasthenia Gravis correlated to COVID-19 in which thymic resection was described and the histologic analysis of the thymus was performed showing thymic hyperplasia despite negative thoracic Magnetic Resonance Imaging. SARS-CoV-2 infection releases inflammatory cytokines that could dysregulate the immune system and lead to Myasthenia Gravis in susceptible subjects.

COVID-19 and Sepsis in an Atypical Case of Mixed Connective Tissue Disorder Presenting With a Myasthenic Crisis.

Myasthenia gravis (MG) is an autoimmune illness that causes neuromuscular junctions to be damaged by anti-acetylcholine receptor antibodies. It is a very rare condition that is more common among women. Fatigable fluctuating diplopia or ptosis is the characteristic early appearance of this condition. Dysphagia or dysphonia may be present in rare cases. This illness can affect any group of skeletal muscles, including those in the neck and upper limbs. It can also affect the muscles that help you breathe, which can lead to breathing failure. We present a case of a 20-year-old female diagnosed with mixed connective tissue disease presenting with acute respiratory failure as the initial presentation of MG. Clinicians have to have a high index of suspicion for myasthenia when patients arrive with fatigable muscle weakness. This will cut down on the amount of money spent on investigations and the risk of morbidity.

The Cumulative Detrimental Effect of COVID-19 Pneumonia in a Patient with Myasthenic Crisis: A Case Report and Overview of the Literature.

BACKGROUND: As the COVID-19 pandemic reached its peak, it became unavoidable that patients with other risk factors for severe pulmonary impairment (such as neuromuscular illnesses) would become afflicted. While the subject of myasthenic crisis secondary to COVID-19 pneumonia represents an interesting topic in the literature, we could not find consistent data that include, as a novel therapeutic approach, both intravenous immunoglobulin and plasma exchange therapy for the treatment of these two concurrent diseases. CASE SUMMARY: A 69-year-old man with known seropositive generalized myasthenia gravis, hypertension, ischaemic heart disease, NYHA class II-III heart failure, cerebrovascular disease, and recurrent urinary tract infections, was admitted to the ICU for mixed acute respiratory failure, elevated serum lactate and liver function enzymes, and severe thrombocytopenia. A SARS-CoV-2 PCR test was positive, despite a previous COVID-19 pneumonia episode, 10 months prior to the current one. The patient had a recent ICU admission for a myasthenic crisis, which required non-invasive mechanical ventilation and intravenous immunoglobulin therapy. He received supportive therapy, as well as etiological (intravenous remdesivir, plasmapheresis and intravenous dexamethasone). Fifteen days after admission, the patient was transferred to the neurological ward, whence he left 20 days later, with no apparent sequelae. CONCLUSIONS: Subsequent intravenous immunoglobulins and plasma exchange therapy appear to be effective and safe in patients with simultaneous acute myasthenic episode and COVID-19 pneumonia.

Acute neuromuscular syndromes with respiratory failure during COVID-19 pandemic: Where we stand and challenges ahead.

Coronavirus disease 2019 (COVID-19), a disease caused by the novel betacoronavirus SARS-COV-2, has become a global pandemic threat. SARS- COV-2 is structurally similar to SARS-COV, and both bind to the angiotensin-converting enzyme 2 (ACE2) receptor to enter human cells. While patients typically present with fever, shortness of breath, sore throat, and cough, in some cases neurologic manifestations occur due to both direct and indirect involvement of the nervous system. Case reports include anosmia, ageusia, central respiratory failure, stroke, acute necrotizing hemorrhagic encephalopathy, toxic-metabolic encephalopathy, headache, myalgia, myelitis, ataxia, and various neuropsychiatric manifestations. Some patients with COVID-19 may present with concurrent acute neuromuscular syndromes such as myasthenic crisis (MC), Guillain-Barré syndrome (GBS) and idiopathic inflammatory myopathies (IIM); these conditions coupled with respiratory failure could trigger a life-threatening condition. Here, we review the current state of knowledge on acute neuromuscular syndromes with respiratory failure related to COVID-19 infection in an attempt to clarify and to manage the muscle dysfunction overlapping SARS-COV-2 infection.

Impact of COVID-19 in AChR Myasthenia Gravis and the Safety of Vaccines: Data from an Italian Cohort.

BACKGROUND AND AIMS: Patients with Myasthenia gravis (MG) are considered vulnerable as they may present with respiratory muscle weakness and because they are on immunosuppressive treatment; thereby, COVID-19 may have a detrimental effect on these patients. Vaccines against COVID-19 are currently available and it has been shown as they can prevent severe COVID-19 in vulnerable patients. Notwithstanding their efficacy, vaccine hesitancy has not been completely dispelled in the general population. Unfortunately, there is limited data about the safety of these vaccines in MG patients. The aims of this study are to evaluate the impact of COVID-19 in a MG cohort, the adherence to COVID-19 vaccination in Italy and vaccine safety in MG patients. METHODS: A retrospective cohort study of MG patients attending the Neuromuscular Clinic of the University Hospital "Paolo Giaccone" of Palermo, Italy, was performed. Patients underwent telephone interviews with a dedicated questionnaire on SARS-CoV-2 vaccination and infection. Vaccine safety was assessed though the evaluation of vaccine-related adverse events (AEs) and comparisons of MG-ADL scores before and after vaccination. Patient worsening was defined as two or more point increases in MG-ADL scores. RESULTS: From a total of 90 participants, 75 answered the questionnaire and 70.5% of them (n = 53) received the vaccine; ten patients did not receive vaccination and 3 patients were partially vaccinated. Among the vaccinated patients, about 45% (n = 24) experienced at least one AE, with a complete resolution within one week. No serious AEs and life-threatening conditions were observed. Globally, MG-ADL scores did not worsen after vaccination. Nine unvaccinated patients experienced SARS-CoV2 infection and four of them (44%) died-one patient required respiratory support, whereas three patients were asymptomatic. CONCLUSIONS: COVID-19 significantly impacted MG patients with an increase in mortality due to respiratory sequelae. Vaccines against SARS-CoV-2 showed good short-term safety in MG patients, who may take advantage of vaccination to avoiding life-threatening complications such as COVID-19 pneumonia.

An Interesting Case of Fatal Myasthenic Crisis Probably Induced by the COVID-19 Vaccine.

A myasthenic crisis is a severe, life-threatening exacerbation of myasthenia gravis that causes a rapid onset of muscle weakness and fatigue that may result in tetraparesis, dyspnea, respiratory insufficiency, aspiration, and death. Bulbar muscle functions are markedly affected resulting in depressed cough reflex, swallowing, and speech. Thus, mechanical ventilation, supportive feeding, and critical care are essential for the survival of patients in a myasthenic crisis. Numerous precipitating factors of this condition are well known and include infections, various medications, pregnancy, and childbirth. Patients with myasthenia gravis are at a considerably higher risk of developing a debilitating coronavirus disease 2019 (COVID-19) infection due to the associated immunosuppression resulting from long-term corticosteroid use, which makes vaccination of such individuals necessary. However, the relationship between an exacerbation of myasthenia gravis and the COVID-19 vaccination is currently unknown. In this paper, we report the case of a 55-year-old male patient who developed a myasthenic crisis after receiving the first dose of the ChAdOx1-S (recombinant) vaccine (AstraZeneca batch number 210157; AstraZeneca plc, Cambridge, United Kingdom). Despite the administration of aggressive and intensive treatment over a period of 29-day hospitalization, the myasthenic crisis could not be reversed and the patient ultimately deteriorated and succumbed from multiple myocardial infarction events and organ failures. While it is still uncommon, evidence associating the effects of the vaccine to the development of a crisis is mounting; therefore, it is crucial for clinicians to promptly identify clinical features that suggest an exacerbation of myasthenia gravis in order to intervene at the earliest possible stage for a more favorable outcome. The myasthenia gravis patient should be informed about the possible association between COVID-19 vaccination and the development of a myasthenic crisis.

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.

COVID-19 in Patients with Myasthenia Gravis: Mechanisms of Respiratory Failure.

This report describes a patient with thymomatous myasthenia gravis (MG) with aplastic anemia in pharmacological remission and COVID-19 who developed respiratory failure in the course of the disease and reviews the published literature on this topic. Analysis of the clinical characteristics of the eight patients with MG including our patient suggests two possible mechanisms for respiratory failure: myasthenic crisis (MC) or pulmonary complications of COVID-19. Patients with MC were young women in high-grade MGFA Class whereas patients with respiratory failure due to pulmonary complications of COVID-19 were elderly men in pharmacological remission or MGFA Class I. These observations suggest that COVID-19, like other infections, may precipitate MC in patients with severe grade MG before COVID-19. The only differentiating feature between the two types of failure was severity myasthenic weakness. This clinical distinction has management implications. These observations need to be validated in a larger sample.

A Complicated Case of Postpartum Myasthenic Crisis.

Myasthenia gravis (MG) is the most common autoimmune disorder affecting the neuromuscular junction (NMJ) of voluntary skeletal muscle. This disease is characterized by ptosis, diplopia, facial muscle weakness, bulbar muscle involvement including dysphagia and difficulty chewing, dysarthria, hypophonia, respiratory muscle fatigue, and sometimes generalized weakness. A myasthenic crisis (MC) is a complication of MG. MC is defined as severe worsening of respiratory function necessitating the need for mechanical ventilation. Precipitating factors include infection, certain drugs, pregnancy, childbirth, surgery, discontinuation of medical therapy, or even spontaneously with no inciting event. Here we present a complicated case of a 24-year-old patient with a long history of controlled who encounters many events that lead to an MC necessitating mechanical intubation, plasmapheresis, and high dose immunosuppressive therapy. She recently gave birth to a child, had an occult perforated appendicitis with multiple abscesses needing emergent exploratory laparotomy, and had an overlying COVID-19 infection. The complexity of this disease and its complications warrants careful consideration by physicians in any branch of specialty.

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 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.

Myasthenia gravis at the crossroad of COVID-19: focus on immunological and respiratory interplay.

Coronavirus disease 2019 (COVID-19), a disease caused by the novel betacoronavirus (SARS-CoV-2) has become a global pandemic threat. COVID-19 caused by SARS-CoV-2 is reported to originate in December 2019 in Wuhan, China and spreading rapidly around world. SARS-CoV-2 is structurally similar to the other coronaviruses, causing the severe respiratory syndrome (SARS-CoV) and the middle east respiratory syndrome (MERS-CoV), both binding to the angiotensin-converting enzyme 2 (ACE2) receptor to enter human cells. ACE 2 is widely expressed in several cells including, neural tissue. COVID-19 presents with fever and respiratory symptoms, possibly leading to acute respiratory distress (ARDS) but there are several published reports of acute cerebrovascular diseases, seizures, olfactory and gustatory dysfunctions, isolated involvement of cranial nerves, myositis/rabdhomyolisis as well myasthenic crisis (MC) and Guillain-Barré syndrome (GBS). The ARDS described during COVID-19 pandemic, coupled with respiratory muscle failure occurring in myasthenia gravis (MG), may result in a life-threatening condition, challenging for intensivists, pulmonologists and neurologists. Infections are recognized trigger of exacerbations and crisis in MG and patients with MG probably exhibit a mortality higher than the general population during this COVID-19 pandemic. We review the current state of knowledge on MG during the COVID-19 pandemic to focus the immunological and respiratory interplay between these two conditions.