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Medicina Clinica Aug 2023Myasthenia gravis is an autoimmune disease caused by the presence of specific antibodies targeting different postsynaptic components of the neuromuscular junction, and... (Review)
Review
Myasthenia gravis is an autoimmune disease caused by the presence of specific antibodies targeting different postsynaptic components of the neuromuscular junction, and is clinically characterized by the presence of fatigueable muscle weakness. In the etiopathogenesis plays a central role the thymus and the most frequently detected pathogenic autoantibodies are targeted to the acetylcholine receptor. The increase in the knowledge of the immunological components of the neuromuscular junction in the last two decades has been fundamental to identify new pathogenic antibodies, reduce the percentage of patients with seronegative myasthenia, and propose a classification of patients into subgroups with clinical-therapeutic interest. In addition, in recent years, new drugs have been developed for the treatment of patients with myasthenia gravis that are refractory to conventional immunosuppressive treatment.
Topics: Humans; Myasthenia Gravis; Neuromuscular Junction; Receptors, Cholinergic; Autoantibodies; Immunosuppressive Agents; Muscle Weakness
PubMed: 37248131
DOI: 10.1016/j.medcli.2023.04.006 -
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 -
The Lancet. Neurology Feb 2022Autoimmune neuromuscular junction disorders are rare. However, myasthenia gravis is being increasingly recognised in people older than 50 years. In the past 5-10 years,... (Review)
Review
Autoimmune neuromuscular junction disorders are rare. However, myasthenia gravis is being increasingly recognised in people older than 50 years. In the past 5-10 years, epidemiological studies worldwide suggest an incidence of acetylcholine receptor antibody-positive myasthenia gravis of up to 29 cases per 1 million people per year. Muscle-specific tyrosine kinase antibody-positive myasthenia gravis and Lambert-Eaton myasthenic syndrome are about 20 times less common. Several diagnostic methods are available for autoimmune neuromuscular junction disorders, including serological antibody, electrophysiological, imaging, and pharmacological tests. The course of disease can be followed up with internationally accepted clinical scores or patient-reported outcome measures. For prognostic purposes, determining whether the disease is paraneoplastic is of great importance, as myasthenia gravis can be associated with thymoma and Lambert-Eaton myasthenic syndrome with small-cell lung cancer. However, despite well defined diagnostic parameters to classify patients into subgroups, objective biomarkers for use in the clinic or in clinical trials to predict the course of myasthenia gravis and Lambert-Eaton myasthenic syndrome are needed.
Topics: Autoantibodies; Biomarkers; Humans; Lambert-Eaton Myasthenic Syndrome; Myasthenia Gravis; Neuromuscular Junction Diseases
PubMed: 35065040
DOI: 10.1016/S1474-4422(21)00297-0 -
Neuromuscular Disorders : NMD Mar 2021Myasthenia gravis is characterized by muscle weakness and fatigue. As sustained muscle use increases the weakness, the value of physical training programs has previously... (Review)
Review
Myasthenia gravis is characterized by muscle weakness and fatigue. As sustained muscle use increases the weakness, the value of physical training programs has previously been questioned. This is a review to clarify the safety and usefulness of systematic training in myasthenia gravis, based on a systematic search in available databases using the relevant key words. Ten intervention studies including 159 patients with generalized disease have been published regarding the effect of systematic physical training, three of them on respiratory muscles. Muscle strength improved, and in the majority of the studies also daily function and quality of life. The feeling of fatigue not directly related to actual muscle weakness was less influenced by physical training. Continuous training was necessary to maintain the improved function. Physical training and exercise are safe in myasthenia gravis. This can improve both muscle strength and daily function. Type and intensity of systematic training should be adapted in the individual patient. A minimum of 150 min of exercise per week is recommended for myasthenia gravis patients with mild and moderate disease.
Topics: Exercise; Fatigue; Female; Humans; Male; Muscle Strength; Muscle Weakness; Myasthenia Gravis; Physical Conditioning, Human; Quality of Life; Respiratory Muscles
PubMed: 33461846
DOI: 10.1016/j.nmd.2020.12.004 -
Drugs Feb 2022Efgartigimod (efgartigimod alfa-fcab, Vyvgart) is a first-in-class neonatal Fc receptor antagonist being developed by argenx for the treatment of autoimmune diseases... (Review)
Review
Efgartigimod (efgartigimod alfa-fcab, Vyvgart) is a first-in-class neonatal Fc receptor antagonist being developed by argenx for the treatment of autoimmune diseases including myasthenia gravis. In December 2021, intravenous efgartigimod received its first approval in the USA for the treatment of generalized myasthenia gravis in adults who are anti-acetylcholine receptor (AChR) antibody positive. Intravenous efgartigimod has also been evaluated for generalized myasthenia gravis in various other countries, with the agent subsequently approved in Japan in January 2022 for generalized myasthenia gravis patients regardless of antibody status and in preregistration stage in the EU. Several clinical studies of intravenous and subcutaneous formulation of efgartigimod are also being investigated for other autoimmune diseases including bullous pemphigoid, chronic inflammatory demyelinating polyradiculoneuropathy, immune thrombocytopenia, autoimmune myositis and pemphigus. This article summarizes the milestones in the development of efgartigimod leading to this first approval for generalized myasthenia gravis.
Topics: Adult; Antibodies, Monoclonal, Humanized; Autoantibodies; Humans; Infant, Newborn; Myasthenia Gravis; Purpura, Thrombocytopenic, Idiopathic; Receptors, Cholinergic
PubMed: 35179720
DOI: 10.1007/s40265-022-01678-3 -
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 -
Current Opinion in Rheumatology Nov 2019This article provides an update on the most recent advances in diagnostic procedures and therapeutic approaches for myasthenia gravis, spanning from autoantibody and... (Review)
Review
PURPOSE OF REVIEW
This article provides an update on the most recent advances in diagnostic procedures and therapeutic approaches for myasthenia gravis, spanning from autoantibody and neuroelectrophysiological tests as diagnostic tools, to innovative and promising treatments based on biological drugs.
RECENT FINDINGS
Novel studies performed by cell-based assays (CBAs) indicate an improvement in the chance of identifying serum autoantibodies in myasthenic patients. Clinical trials on the use of biological drugs were recently concluded, providing important data on safety and efficacy of eculizumab, efgartigimod and amifampridine phosphate: the first, a complement blocker, showed long-term safety and efficacy in acetylcholine receptor (AChR)-positive myasthenic patients with refractory generalized disease; the second, the neonatal Fc receptor blocker, was well tolerated and clinically effective in both AChR-specific and muscle-specific kinase receptor (MuSK)-positive patients; the third, a blocker of presynaptic potassium channels, was found to be well tolerated and effective in MuSK-positive patients.
SUMMARY
CBAs can lead to a significant reduction of seronegative patients, improving myasthenia gravis diagnostic process. New biological drugs offer innovative approaches to treat myasthenic patients with generalized disease, promising to change the paradigm of treatment and to significantly enhance therapeutic success within a precision medicine framework.
Topics: Autoantibodies; Biological Factors; Electromyography; Humans; Immunosuppressive Agents; Myasthenia Gravis; Treatment Outcome
PubMed: 31385879
DOI: 10.1097/BOR.0000000000000647 -
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 -
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 -
Neurologic Clinics Feb 2021Myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) are the most common disorders of neuromuscular transmission in clinical practice. Disorders of the... (Review)
Review
Myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) are the most common disorders of neuromuscular transmission in clinical practice. Disorders of the neuromuscular junction (NMJ) are characterized by fluctuating and fatigable weakness and include autoimmune, toxic, and genetic conditions. Adults with NMJ disorders are most often antibody mediated, with MG being the most common, having a prevalence of approximately 1 in 10,000, and with women being affected about twice as often as men. This article focuses on advances in management of autoimmune MG and LEMS.
Topics: Adult; Female; Humans; Lambert-Eaton Myasthenic Syndrome; Male; Myasthenia Gravis
PubMed: 33223079
DOI: 10.1016/j.ncl.2020.09.007