Myasthenia Gravis

2013 ◽  
Author(s):  
Aaron E. Miller ◽  
Teresa M. DeAngelis
Keyword(s):  
Surgical Treatment ◽  
Neuromuscular Junction ◽  
Myasthenia Gravis ◽  
Acetylcholine Receptors ◽  
Diagnostic Testing ◽  
Autoimmune Disorder ◽  
Postsynaptic Membrane ◽  
Treatment Recommendations ◽  
Clinical Findings

Myasthenia gravis (MG) is an autoimmune disorder that results in loss of functional acetylcholine receptors (AChR) on the postsynaptic membrane of the neuromuscular junction caused by the presence of antibodies to the AChR. In this chapter, we review the cardinal clinical findings of MG, the standard diagnostic testing including electrophysiological features, and the medical and surgical treatment recommendations.

Other Proven and Putative Autoimmune Disorders of the Peripheral Nervous System

2017 ◽  
Author(s):  
Doris G. Leung
Keyword(s):  
Neuromuscular Junction ◽  
Myasthenia Gravis ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Autoimmune Disorder ◽  
Synaptic Proteins ◽  
Disease Treatment ◽  
Nicotinic Acetylcholine ◽  
System P ◽  
Presynaptic Calcium

Myasthenia gravis is in most cases an autoimmune disorder of the neuromuscular junction in which antibodies are directed at nicotinic acetylcholine receptors or other synaptic proteins, such as the MusK protein that is involved in the formation of the formation and maturation of the motor endplate. Less commonly, myasthenia gravis can result from antibodies directed to presynaptic calcium channels as a side effect of paraneoplastic antibodies (Lambert-Eaton syndrome) or from a developmental paucity of acetylcholine receptors in the neonatal form of the disease. Treatment is usually a combination of aceetylcoholinesterase inhibitors such as pyridostigmine to prolong the life of acetylcholine released at the neuromuscular junction and/or drugs such as corticosteroids aimed at reducing inflammation.

Rituximab in AChR subtype of myasthenia gravis: systematic review

2020 ◽  
Vol 91 (4) ◽  
pp. 392-395 ◽  
Author(s):  
Vincenzo Di Stefano ◽  
Antonino Lupica ◽  
Marianna Gabriella Rispoli ◽  
Antonio Di Muzio ◽  
Filippo Brighina ◽  
...  
Keyword(s):  
Systematic Review ◽  
Neuromuscular Junction ◽  
Myasthenia Gravis ◽  
Acetylcholine Receptor ◽  
Autoimmune Disorder ◽  
Postsynaptic Membrane ◽  
Receptor Subtype ◽  
Registration Number ◽  
Randomised Controlled ◽  
Time To Relapse

Myasthenia gravis (MG) is a chronic autoimmune disorder of the neuromuscular junction characterised by an autoantibody against acetylcholine receptor (AChR-Ab), autoantibody against muscle-specific kinase (MuSK-Ab), lipoprotein-related protein 4 or agrin in the postsynaptic membrane at the neuromuscular junction. Many patients are resistant to conventional treatment and effective therapies are needed. Rituximab (RTX) is a monoclonal antibody directed against CD20 antigen on B cells which has been successfully employed in anti-MuSK-Ab+MG, but the efficacy in anti-AChR-Ab+MG is still debated. The purpose of this systematic review was to describe the best evidence for RTX in the acetylcholine receptor subtype. The authors undertook a literature search during the period of 1999–2019 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analys methodology, employing (myasthenia)+(gravis)+(RTX) as search terms. The analysis was confined to studies that include at least five patients with confirmed anti-AChR-Ab+MG. Thirteen studies have been selected, showing a good safety. The data obtained were heterogeneous in terms of posology, administration scheme and patients’ evaluation, ranging from a minimum of two to a maximum of three cycles. RTX led to a sustained clinical improvement with prolonged time to relapse, in parallel to a reduction or discontinuation of other immunosuppressive therapies. Treatment with RTX appears to work in some but not all patients with anti-AChR-Ab+MG, but randomised controlled trials are needed. Future studies should take into account the subtype of MG and employ reliable measures of outcome and severity focusing on how to identify patients who may benefit from the treatment. Trial registration number: NCT02110706.

MYASTHENIA GRAVIS: A SERUM FACTOR BLOCKING ACETYLCHOLINE RECEPTORS OF THE HUMAN NEUROMUSCULAR JUNCTION

The Lancet ◽  
1975 ◽  
Vol 305 (7907) ◽  
pp. 607-609 ◽  
Author(s):  
AdamN Bender ◽  
W King Engel ◽  
StevenP Ringel ◽  
MathewP Daniels ◽  
Zvi Vogel
Keyword(s):  
Neuromuscular Junction ◽  
Myasthenia Gravis ◽  
Acetylcholine Receptors ◽  
Serum Factor

scholarly journals Processing of ARIA and release from isolated nerve terminals

1999 ◽  
Vol 354 (1381) ◽  
pp. 411-416 ◽  
Author(s):  
Bomie Han ◽  
Gerald D. Fischbach
Keyword(s):  
Neuromuscular Junction ◽  
Action Potential ◽  
Acetylcholine Receptors ◽  
Molecular Layer ◽  
Postsynaptic Membrane ◽  
High Density ◽  
Small Contribution ◽  
Presynaptic Nerve Terminal ◽  
Voltage Gated

The neuromuscular junction is a specialized synapse in that every action potential in the presynaptic nerve terminal results in an action potential in the postsynaptic membrane, unlike most interneuronal synapses where a single presynaptic input makes only a small contribution to the population postsynaptic response. The postsynaptic membrane at the neuromuscular junction contains a high density of neurotransmitter (acetylcholine) receptors and a high density of voltage–gated Na + channels. Thus, the large acetylcholine activated current occurs at the same site where the threshold for action potential generation is low. Acetylcholine receptor inducing activity (ARIA), a 42 kD protein, that stimulates synthesis of acetylcholine receptors and voltage–gated Na + channels in cultured myotubes, probably plays the same roles at developing and mature motor endplates in vivo . ARIA is synthesized as part of a larger, transmembrane, precursor protein called proARIA. Delivery of ARIA from motor neuron cell bodies in the spinal cord to the target endplates involves several steps, including proteolytic cleavage of proARIA. ARIA is also expressed in the central nervous system and it is abundant in the molecular layer of the cerebellum. In this paper we describe our first experiments on the processing and release of ARIA from subcellular fractions containing synaptosomes from the chick cerebellum as a model system.

scholarly journals Fc-Receptor Targeted Therapies for the Treatment of Myasthenia gravis

2021 ◽  
Vol 22 (11) ◽  
pp. 5755
Author(s):  
Christian W. Keller ◽  
Marc Pawlitzki ◽  
Heinz Wiendl ◽  
Jan D. Lünemann
Keyword(s):  
Myasthenia Gravis ◽  
Acetylcholine Receptors ◽  
Postsynaptic Membrane ◽  
Fc Receptor ◽  
Igg Antibodies ◽  
Effector Functions ◽  
Disease Remission ◽  
Disease Mechanisms ◽  
First Choice ◽  
Complement Deposition

Myasthenia gravis (MG) is an autoimmune disease in which immunoglobulin G (IgG) antibodies (Abs) bind to acetylcholine receptors (AChR) or to functionally related molecules in the postsynaptic membrane at the neuromuscular junction. IgG crystallizable fragment (Fc)-mediated effector functions, such as antibody-dependent complement deposition, contribute to disease development and progression. Despite progress in understanding Ab-mediated disease mechanisms, immunotherapy of MG remained rather unspecific with corticosteroids and maintenance with immunosuppressants as first choice drugs for most patients. More specific therapeutic IgG Fc-based platforms that reduce serum half-life or effector functions of pathogenic MG-related Abs are currently being developed, tested in clinical trials or have recently been successfully translated into the clinic. In this review, we illustrate mechanisms of action and clinical efficacies of emerging Fc-mediated therapeutics such as neonatal Fc receptor (FcRn)-targeting agents. Furthermore, we evaluate prospects of therapies targeting classical Fc receptors that have shown promising therapeutic efficacy in other antibody-mediated conditions. Increased availability of Fc- and Fc receptor-targeting biologics might foster the development of personalized immunotherapies with the potential to induce sustained disease remission in patients with MG.

Neuromuscular Junction in Myasthenia Gravis: Decreased Acetylcholine Receptors

Science ◽  
1973 ◽  
Vol 182 (4109) ◽  
pp. 293-295 ◽  
Author(s):  
D. M. Fambrough ◽  
D. B. Drachman ◽  
S. Satyamurti
Keyword(s):  
Neuromuscular Junction ◽  
Myasthenia Gravis ◽  
Acetylcholine Receptors

scholarly journals Pathogenesis of myasthenia gravis: update on disease types, models, and mechanisms

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 1513 ◽  
Author(s):  
William D. Phillips ◽  
Angela Vincent
Keyword(s):  
Neuromuscular Junction ◽  
Myasthenia Gravis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Respiratory Muscles ◽  
Postsynaptic Membrane ◽  
Synaptic Function ◽  
Density Lipoprotein Receptor ◽  
Synapse Maintenance ◽  
Muscle Groups

Myasthenia gravis is an autoimmune disease of the neuromuscular junction (NMJ) caused by antibodies that attack components of the postsynaptic membrane, impair neuromuscular transmission, and lead to weakness and fatigue of skeletal muscle. This can be generalised or localised to certain muscle groups, and involvement of the bulbar and respiratory muscles can be life threatening. The pathogenesis of myasthenia gravis depends upon the target and isotype of the autoantibodies. Most cases are caused by immunoglobulin (Ig)G1 and IgG3 antibodies to the acetylcholine receptor (AChR). They produce complement-mediated damage and increase the rate of AChR turnover, both mechanisms causing loss of AChR from the postsynaptic membrane. The thymus gland is involved in many patients, and there are experimental and genetic approaches to understand the failure of immune tolerance to the AChR. In a proportion of those patients without AChR antibodies, antibodies to muscle-specific kinase (MuSK), or related proteins such as agrin and low-density lipoprotein receptor-related protein 4 (LRP4), are present. MuSK antibodies are predominantly IgG4 and cause disassembly of the neuromuscular junction by disrupting the physiological function of MuSK in synapse maintenance and adaptation. Here we discuss how knowledge of neuromuscular junction structure and function has fed into understanding the mechanisms of AChR and MuSK antibodies. Myasthenia gravis remains a paradigm for autoantibody-mediated conditions and these observations show how much there is still to learn about synaptic function and pathological mechanisms.

scholarly journals Muscle-Specific Tyrosine Kinase-Associated Myasthenia Gravis: A Neuromuscular Surprise

2021 ◽  
Vol 2021 ◽  
pp. 1-3
Author(s):  
Hassam Ali ◽  
Rahul Pamarthy ◽  
Nayab Ahsan ◽  
WashmaAwan ◽  
Shiza Sarfraz
Keyword(s):  
Neuromuscular Junction ◽  
Tyrosine Kinase ◽  
Myasthenia Gravis ◽  
Muscle Weakness ◽  
Acetylcholine Receptors ◽  
Muscular Contraction ◽  
Skeletal Muscle Weakness ◽  
Hypoxic Respiratory Failure ◽  
Receptor Antibodies

Myasthenia gravis is a neuromuscular autoimmune disease that results in skeletal muscle weakness that worsens after periods of activity and improves after rest. Myasthenia gravis means “grave (serious), muscle weakness.” Although not completely curable, it can be managed well with a relatively high quality of life and expectancy. In myasthenia gravis, antibodies against the acetylcholine receptors at the neuromuscular junction interfere with regular muscular contraction. Although most commonly caused by antibodies to the acetylcholine receptor, antibodies against MuSK (muscle-specific kinase) protein can also weaken transmission at the neuromuscular junction. Muscle-specific tyrosine kinase myasthenia gravis (MuSK-Ab MG) is a rare subtype of myasthenia gravis with distinct pathogenesis and unique clinical features. Diagnosis can be challenging due to its atypical presentation as compared to seropositive myasthenia gravis. It responds inconsistently to steroids, but plasma exchange and immunosuppressive therapies have shown promising results. We report a case of a 49-year-old female who presented with acute hypoxic respiratory failure. Our patient experienced progressive, undiagnosed MuSK-Ab MG for years without a diagnosis.

scholarly journals Specific features of anesthesia in patients with myasthenia gravis

2016 ◽  
Vol 69 (9-10) ◽  
pp. 305-311
Author(s):  
Ivana Spasojevic ◽  
Danica Hajdukovic ◽  
Milena Komarcevic ◽  
Stanislava Petrovic ◽  
Jelena Jovanovic ◽  
...  
Keyword(s):  
Surgical Treatment ◽  
Conservative Treatment ◽  
Myasthenia Gravis ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Surgical Interventions ◽  
Different Types ◽  
Increased Sensitivity ◽  
Tensilon Test

Introduction. Myasthenia gravis is an autoimmune disease caused by antibodies leading to the destruction of nicotinic acetylcholine receptors on the neuromuscular junction. It is characterized by muscle weakness that gets aggravated with physical activity and improves at rest. Myasthenia Gravis Foundation of America made the clinical classification of Myasthenia gravis which is still in use today. ?Tensilon test? is still the gold standard for the diagnosis of Myasthenia gravis. In addition to this test repeated muscular stimulation can be used as well as the analysis of specific autoantibodies. Treatment of Myasthenia Gravis. In conservative treatment of Mysthenia gravis anticholinesterases, immunosuppressants and plasmapheresis can be used. If conservative treatment does not lead to the desired remission, surgical treatment is indicated. The most accepted indication for thymectomy is the presence of thymoma with generalized form of Myasthenia gravis in adults. How to Distinguish Myasthenic From Cholinergic Crisis. The following is important to make a difference between these two crises: knowledge of the events that preceded the crisis, the size of pupils as well as the presence of muscarinic signs and tensilon test. Specific Features of Anesthesia in Patients with Myasthenia Gravis. Mechanism of the disease development is the reason for the increased sensitivity or resistance of these patients to certain types of drugs used in anesthesia. Protocol of Perioperative Anesthesia in Patients with Myasthenia Gravis. Based on 35 years of experience in the surgical treatment of patients with Myasthenia gravis anesthesiologists at the Department of Thoracic Surgery, Institute for Pulmonary Diseases of Vojvodina, made the protocol of anesthesia and perioperative treatment for these patients. Conclusion. Anesthesiologists may have to deal with a patient with myasthenia gravis in different types of surgical interventions. The protocol for anesthesia and perioperative management of these patients herewith presented may greatly help them in their clinical practice.

scholarly journals Myasthenia Gravis Exacerbation and Myasthenic Crisis Associated With COVID19: Case Series and Literature Review.

2021 ◽  
Author(s):  
Cleonisio Leite Rodrigues ◽  
Hermany Capistrano Freitas ◽  
Paulo Reges Oliveira Lima ◽  
Pedro Helder de Oliveira Junior ◽  
José Marcelino Aragão Fernandes ◽  
...  
Keyword(s):  
Literature Review ◽  
Neuromuscular Junction ◽  
Hospital Mortality ◽  
Myasthenia Gravis ◽  
Viral Infections ◽  
Case Series ◽  
Previous Treatment ◽  
Autoimmune Disorder ◽  
Myasthenic Crisis

Abstract Myasthenia Gravis (MG) is an autoimmune disorder of the neuromuscular junction that can be exacerbated by many viral infections, including COVID19. Management of MG exacerbations is challenging in this scenario. We report 8 cases of MG exacerbation or myasthenic crisis associated with COVID19 and discuss prognosis and treatment based on a literature review. 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. This is the largest case series of MG exacerbation or myasthenic crisis due to COVID19 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.

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