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Neurology Jan 2021To update the 2016 formal consensus-based guidance for the management of myasthenia gravis (MG) based on the latest evidence in the literature. (Review)
Review
OBJECTIVE
To update the 2016 formal consensus-based guidance for the management of myasthenia gravis (MG) based on the latest evidence in the literature.
METHODS
In October 2013, the Myasthenia Gravis Foundation of America appointed a Task Force to develop treatment guidance for MG, and a panel of 15 international experts was convened. The RAND/UCLA appropriateness method was used to develop consensus recommendations pertaining to 7 treatment topics. In February 2019, the international panel was reconvened with the addition of one member to represent South America. All previous recommendations were reviewed for currency, and new consensus recommendations were developed on topics that required inclusion or updates based on the recent literature. Up to 3 rounds of anonymous e-mail votes were used to reach consensus, with modifications to recommendations between rounds based on the panel input. A simple majority vote (80% of panel members voting "yes") was used to approve minor changes in grammar and syntax to improve clarity.
RESULTS
The previous recommendations for thymectomy were updated. New recommendations were developed for the use of rituximab, eculizumab, and methotrexate as well as for the following topics: early immunosuppression in ocular MG and MG associated with immune checkpoint inhibitor treatment.
CONCLUSION
This updated formal consensus guidance of international MG experts, based on new evidence, provides recommendations to clinicians caring for patients with MG worldwide.
Topics: Antibodies, Monoclonal, Humanized; Consensus; Disease Management; Humans; Immune Checkpoint Inhibitors; Immunosuppressive Agents; Methotrexate; Myasthenia Gravis; Rituximab; Thymectomy
PubMed: 33144515
DOI: 10.1212/WNL.0000000000011124 -
Neurologic Clinics May 2018With specialized care, patients with myasthenia gravis can have very good outcomes. The mainstays of treatment are acetylcholinesterase inhibitors, and immunosuppressive... (Review)
Review
With specialized care, patients with myasthenia gravis can have very good outcomes. The mainstays of treatment are acetylcholinesterase inhibitors, and immunosuppressive and immunomodulatory therapies. There is good evidence thymectomy is beneficial in thymomatous and nonthymomatous disease. Nearly all of the drugs used for MG are considered "off-label." The 2 exceptions are acetylcholinesterase inhibitors and complement inhibition with eculizumab, which was recently approved by the US Food and Drug Administration for myasthenia gravis. This article reviews the evidence base and provides a framework for the treatment of myasthenia gravis, highlighting recent additions to the literature.
Topics: Humans; Immunosuppressive Agents; Myasthenia Gravis; Thymectomy
PubMed: 29655452
DOI: 10.1016/j.ncl.2018.01.011 -
Arquivos de Neuro-psiquiatria May 2022Myasthenia gravis is largely a treatable disease, but it can result in significant morbidity and even mortality, which can usually be avoided, or at least mitigated,... (Review)
Review
BACKGROUND
Myasthenia gravis is largely a treatable disease, but it can result in significant morbidity and even mortality, which can usually be avoided, or at least mitigated, with timely diagnosis and appropriate treatment of the disease. Objective: this review aims to summarize the main practical aspects of the diagnostic approach, treatment and care of myasthenic patients.
METHODS
The authors performed a non-systematic critical review summarizing the main practical aspects of myasthenia gravis.
RESULTS
Most patients with myasthenia have autoantibodies targeted at acetylcholine receptors or, less commonly, muscle-specific kinase - MuSK. Electrophysiology plays an important role in the diagnosis of neuromuscular junction dysfunction. The central clinical manifestation of myasthenia gravis is fatigable muscle weakness, which can affect eye, bulbar, respiratory, and limb muscles. With rare exceptions, patients have a good response to symptomatic treatment, but corticosteroids and/or immunosuppressants are usually also necessary to obtain good control of the manifestations of the disease.
CONCLUSION
Knowledge of the peculiar aspects of their clinical and electrophysiological presentations is important for the diagnosis. Likewise, specific treatment and response time to each drug are crucial for proper care.
Topics: Autoantibodies; Humans; Muscle Weakness; Myasthenia Gravis; Neuromuscular Junction; Receptor Protein-Tyrosine Kinases; Receptors, Cholinergic
PubMed: 35976295
DOI: 10.1590/0004-282X-ANP-2022-S105 -
Journal of Medicine and Life 2021Neuromuscular junction (NMJ) disorders include several dysfunctions that ultimately lead to muscle weakness. Myasthenia gravis (MG) is the most prevalent NMJ disorder... (Review)
Review
Neuromuscular junction (NMJ) disorders include several dysfunctions that ultimately lead to muscle weakness. Myasthenia gravis (MG) is the most prevalent NMJ disorder with a highly polymorphic clinical presentation and many different faces. Being an autoimmune disease, MG correlates with the presence of detectable antibodies directed against the acetylcholine receptor, muscle-specific kinase, lipoprotein-related protein 4, agrin, titin, and ryanodine in the postsynaptic membrane at the NMJ. MG has become a prototype serving to understand both autoimmunity and the function of the NMJ better. The aim of this review is to synthesize some of the epidemiological data available. Epidemiological data regarding MG are important for postulating hypotheses regarding its etiology and facilitating the description of MG subtypes. Thus, adequate documentation through broad databases is essential. The incidence and prevalence of MG reported around the globe have been rising steadily and consistently over the past decades. Ethnic aspects, gender-related differences, and environmental risk factors have been described, implying that these might contribute to a specific phenotype, further suggesting that MG may be considered an umbrella term that covers several clinical entities.
Topics: Age Factors; Genetic Predisposition to Disease; Humans; Incidence; Myasthenia Gravis; Prevalence; Risk Factors
PubMed: 33767779
DOI: 10.25122/jml-2020-0145 -
Cleveland Clinic Journal of Medicine Feb 2023Myasthenia gravis is a disorder of neuromuscular junction transmission, the result of antibodies against the post-synaptic aspect of the neuromuscular junction. Its... (Review)
Review
Myasthenia gravis is a disorder of neuromuscular junction transmission, the result of antibodies against the post-synaptic aspect of the neuromuscular junction. Its clinical hallmark is fatigable weakness of skeletal muscles, which tends to vary in location and severity among patients. It is treated with pyridostigmine, immunotherapy, and thymectomy. Treatment is often individualized according to disease severity, antibody status, comorbidities, and other factors. This review uses a question-and-answer format to provide up-to-date, high-yield, clinically relevant information on myasthenia gravis.
Topics: Humans; Myasthenia Gravis; Muscle, Skeletal; Muscle Weakness
PubMed: 36724914
DOI: 10.3949/ccjm.90a.22017 -
Clinical & Experimental Optometry Mar 2022Myasthenia gravis is a rare autoimmune disease characterised by autoantibodies preventing normal function of acetylcholine receptors at the post-synaptic membrane of the... (Review)
Review
Myasthenia gravis is a rare autoimmune disease characterised by autoantibodies preventing normal function of acetylcholine receptors at the post-synaptic membrane of the neuromuscular junction. This causes weakness of skeletal muscles that can be variable and fatigable, and often manifests as ptosis and/or diplopia, with 60% of patients demonstrating ocular features at onset, and thus may present initially to eye care practitioners. Approximately 15% of patients have ocular myasthenia gravis, where symptoms remain restricted to this distribution. The majority of patients have blocking antibodies against the acetylcholine receptor, but antibodies directed against other related targets account for a smaller proportion and are associated with specific phenotypes. Associations with both thymoma and with other autoimmune phenomena (particularly thyroid disease) can occur. Clinical examination can identify characteristic findings including fatigable ptosis and Cogan's lid twitch sign. Investigations to confirm the diagnosis include simple office-based procedures such as the ice test, and testing for serum autoantibodies, as well as electrophysiological testing such as repetitive nerve stimulation and single-fibre electromyography. The management of ocular myasthenia gravis is discussed, including non-pharmacological options, pyridostigmine, corticosteroids, other immunosuppressive agents, and thymectomy. The goals of management are to alleviate symptoms, and where possible prevent chronic disability or progression to generalised myasthenia gravis.
Topics: Diplopia; Humans; Immunosuppressive Agents; Myasthenia Gravis
PubMed: 35157811
DOI: 10.1080/08164622.2022.2029683 -
Revista de Neurologia Sep 2022Myasthenia gravis is characterized by skeletal muscle weakness, the most common initial presentation includes ocular weakness with asymmetric ptosis and binocular... (Review)
Review
INTRODUCTION
Myasthenia gravis is characterized by skeletal muscle weakness, the most common initial presentation includes ocular weakness with asymmetric ptosis and binocular diplopia. Around 19-50% of pregnant women with myasthenia gravis will experience a worsening of the disease. The objective of this article was to review the current information regarding the interrelation between MG and pregnancy; as well as its approach.
DEVELOPMENT
Bibliographic search in databases such as PubMed, ScienceDirect, SciELO, Google Scholar and medRxiv. Original articles, reviews, series and case reports between 2013 and 2022 are included.
CONCLUSIONS
Myasthenia gravis would not significantly effects on pregnancy; however, pregnancy can exacerbate the disease, especially during the first trimester or after delivery. The approach to pregnant women with myasthenia gravis must be multidisciplinary and involves the adjustment of pharmacological treatment and constant monitoring.
Topics: Blepharoptosis; Diplopia; Eye; Female; Humans; Muscle Weakness; Myasthenia Gravis; Pregnancy
PubMed: 35880965
DOI: 10.33588/rn.7505.2022207 -
Frontiers in Immunology 2023Myasthenia gravis (MG) is a neuromuscular autoimmune disorder characterized by chronic but intermittent fatigue of the eye- and general body muscles. Muscle weakness is... (Review)
Review
Myasthenia gravis (MG) is a neuromuscular autoimmune disorder characterized by chronic but intermittent fatigue of the eye- and general body muscles. Muscle weakness is caused primarily by the binding of an autoantibody to the acetylcholine receptors, resulting in blockage of normal neuromuscular signal transmission. Studies revealed substantial contributions of different proinflammatory or inflammatory mediators in the pathogenesis of MG. Despite these findings, compared to therapeutic approaches that target autoantibody and complements, only a few therapeutics against key inflammatory molecules have been designed or tested in MG clinical trials. Recent research focuses largely on identifying unknown molecular pathways and novel targets involved in inflammation associated with MG. A well-designed combination or adjunct treatment utilizing one or more selective and validated promising biomarkers of inflammation as a component of targeted therapy may yield better treatment outcomes. This review briefly discusses some preclinical and clinical findings of inflammation associated with MG and current therapy approaches and suggest the potential of targeting important inflammatory marker(s) along with current monoclonal antibody or antibody fragment based targeted therapies directed to a variety of cell surface receptors.
Topics: Humans; Myasthenia Gravis; Receptors, Cholinergic; Autoantibodies; Muscles; Inflammation
PubMed: 36793733
DOI: 10.3389/fimmu.2023.1110499 -
Journal of Veterinary Internal Medicine Sep 2020Myasthenia, a syndrome of impaired neuromuscular transmission, occurs as either an acquired or congenital condition. Myasthenia gravis (MG) is an acquired autoimmune... (Review)
Review
Myasthenia, a syndrome of impaired neuromuscular transmission, occurs as either an acquired or congenital condition. Myasthenia gravis (MG) is an acquired autoimmune disorder with autoantibodies against the neuromuscular junction (NMJ) of skeletal muscle whereas congenital myasthenic syndromes (CMSs) are a clinically heterogeneous group of genetic disorders affecting the NMJ with a young age of onset. Both conditions are diseases for which recognition is important with regard to treatment and outcome. We review the published literature on MG and CMSs in dogs and cats, and by comparison with published classification used in humans, propose a classification system for MG and CMSs in dogs and cats. Myasthenia gravis is first classified based on focal, generalized, or acute fulminating presentation. It then is subclassified according to the autoimmune disease mechanism or seronegativity. Autoimmune disease mechanism relates to the presence or absence of a thymoma, or administration of thiourylene medication in cats. Congenital myasthenic syndromes are classified according to the affected NMJ component, the mechanism of the defect of neuromuscular transmission, the affected protein, and ultimately the mutated gene responsible. In proposing this categorization of MG and CMSs, we hope to aid recognition of the disease groups for both conditions, as well as guide treatment, refine prognosis, and provide a framework for additional studies of these conditions.
Topics: Animals; Cat Diseases; Cats; Dog Diseases; Dogs; Myasthenia Gravis; Myasthenic Syndromes, Congenital; Neuromuscular Junction
PubMed: 32668077
DOI: 10.1111/jvim.15855 -
Journal of Neurology Apr 2016Myasthenia gravis (MG) is the archetypic disorder of both the neuromuscular junction and autoantibody-mediated disease. In most patients, IgG1-dominant antibodies to... (Review)
Review
Myasthenia gravis (MG) is the archetypic disorder of both the neuromuscular junction and autoantibody-mediated disease. In most patients, IgG1-dominant antibodies to acetylcholine receptors cause fatigable weakness of skeletal muscles. In the rest, a variable proportion possesses antibodies to muscle-specific tyrosine kinase while the remainder of seronegative MG is being explained through cell-based assays using a receptor-clustering technique and, to a lesser extent, proposed new antigenic targets. The incidence and prevalence of MG are increasing, particularly in the elderly. New treatments are being developed, and results from the randomised controlled trial of thymectomy in non-thymomatous MG, due for release in early 2016, will be of particular clinical value. To help navigate an evidence base of varying quality, practising clinicians may consult new MG guidelines in the fields of pregnancy, ocular and generalised MG (GMG). This review focuses on updates in epidemiology, immunology, therapeutic and clinical aspects of GMG in adults.
Topics: Female; Humans; Male; Myasthenia Gravis
PubMed: 26705120
DOI: 10.1007/s00415-015-7963-5