Diagnosis, assessment, and management of myasthenia gravis and paramyasthenic syndromes

2016 ◽  
Author(s):  
Ugan Reddy ◽  
Nicholas Hirsch
Keyword(s):  
Autoimmune Disease ◽  
Myasthenia Gravis ◽  
Muscle Weakness ◽  
Motor Nerve ◽  
Neuromuscular Blocking ◽  
Myasthenic Crisis ◽  
Igg Antibodies ◽  
Limb Weakness ◽  
Myasthenic Syndrome ◽  
Long Acting

Diseases that affect the neuromuscular junction (NMJ) interfere with normal nerve transmission and cause weakness of voluntary muscles. The two most commonly encountered are acquired myasthenia gravis (MG) and the Lambert–Eaton myasthenic syndrome (LEMS). Acquired MG is an autoimmune disease in which antibodies are directed towards receptors at the NMJ. In 85% of patients, IgG antibodies against the postsynaptic acetylcholine receptor (AChR) are found (seropositive MG). The thymus gland appears to be involved in the production of these which cause an increase rate of degradation of AChR resulting in a decreased receptor density resulting in a reduced postsynaptic end-plate potential following motor nerve stimulation and leading to muscle weakness. Although all voluntary muscles can be affected, ocular, bulbar, respiratory, and proximal limb weakness predominates. In the majority of seronegative patients, an antibody directed towards a NMJ protein called muscle specific tyrosine kinase (MUSK) is found. Anti-MUSK MG is characterized by severe bulbar and respiratory muscle weakness. Diagnosis of MG requires a high degree of clinical suspicion coupled with pharmacological and electrophysiological testing, and detection of the various causative antibodies. Treatment of MG involves enhancing neuromuscular transmission with long-acting anticholinesterase agents and immunosuppression. Acute exacerbations are treated with either plasma exchange or intravenous immunoglobulin. Myasthenic crisis is associated with severe muscle weakness that necessitates tracheal intubation and mechanical ventilation. LEMS is an autoimmune disease in which IgG antibodies are directed towards the pre-synaptic voltage-gated calcium channels at the NMJ. It is often associated with malignant disease (usually small cell carcinoma of the lung). Autonomic dysfunction is prominent and patients show abnormal responses to neuromuscular blocking drugs.

Myasthenia Gravis Patient Presenting for Ureteroscopy

2018 ◽  
pp. 287-294
Author(s):  
Theresa J. Barnes ◽  
Amanda Moraska Benson ◽  
Ashish K. Khanna
Keyword(s):  
Myasthenia Gravis ◽  
Muscle Weakness ◽  
Respiratory Insufficiency ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Neuromuscular Blocking ◽  
Myasthenic Crisis ◽  
Respiratory Impairment ◽  
Skeletal Muscle Weakness ◽  
Autoimmune Condition

Myasthenia gravis (MG) is an autoimmune condition, most commonly affecting middle-aged women and older males, caused by antibody-mediated attack of the postsynaptic nicotinic acetylcholine receptors at the neuromuscular junction. The resulting skeletal muscle weakness can be highly variable, ranging from fatigue of ocular muscles only to significant respiratory impairment with peripheral muscle weakness. MG has multiple important implications for anesthesiologists. This surgical case explores the pathophysiology of MG, common treatments, preoperative anesthetic assessment, intraoperative considerations, implications for anesthetic drug interactions, predictors of postoperative respiratory insufficiency, and a review of postoperative concerns and complications. Topics covered include myasthenic crisis, postoperative respiratory insufficiency, anticholinesterase, neuromuscular blocking drugs, thymectomy, and extubation criteria.

Expecting the unexpected.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14066-e14066
Author(s):  
Blessie Elizabeth Nelson ◽  
Adrian Gerard Murphy ◽  
Jacquelyn W. Zimmerman
Keyword(s):  
Myasthenia Gravis ◽  
Muscle Weakness ◽  
De Novo ◽  
Early Recognition ◽  
Compound Muscle Action Potential ◽  
Care Center ◽  
Tertiary Care ◽  
Sudden Onset ◽  
Shoulder Abduction ◽  
Myasthenic Crisis

e14066 Background: Myasthenia gravis is an autoimmune neuro-muscular disorder traditionally seen in bi-modal distribution in young women or older men. Discovery of immunotherapy has brought hope in survival outcomes for patients with malignant melanoma, lung, renal and head/neck cancers but it also opens Pandora’s box of immune-related toxicities for which early recognition and appropriate clinical management are paramount. Here we describe a case of immunotherapy induced myasthenia gravis de novo. Methods: A 77-year-old man with HPV+ stage IVA squamous cell carcinoma of the tongue presented with sudden onset orthopnea and dyspnea on exertion for the past day. One week ago, he received his second cycle of nivolumab as part of his neoadjuvant therapy. He was seen at an outside hospital and was found to be acute hypercapnic respiratory failure and placed on BiPAP. He was started on antibiotics for community-acquired pneumonia with levofloxacin and doxycycline and transferred to a tertiary care center for further management. On further evaluation, he endorsed diplopia, blurry vision, fluctuating muscle weakness that is worse at the end of the day, change in voice and proximal muscle weakness. His exam was consistent with bilateral ptosis, weak hip flexion and shoulder abduction, positive sniff test and poor vital capacity and negative inspiratory force values suggestive of impending respiratory and diaphragmatic failure secondary to myasthenic crisis. He was admitted to the ICU and placed on BiPAP and frequent NIF and VC monitoring. He was started on pyridostigmine but showed no clinical improvement on day 1 and hence was initiated on plasmapheresis from day 2 for a total of 10 days. Results: Investigations showed positivity of Ach-R modulating and binding and blocking antibodies with negative voltage gated calcium channel antibodies. EMG revealed decrement of the compound muscle action potential in the repetitive stimulation test indicative of myasthenia gravis. He responded well to the above treatment and underwent successful left partial glossectomy and weaned off mechanical ventilation and has been cancer free so far. He is doing well on maintenance prednisone and pyridostigmine. Conclusions: There is a significant 30.4% MG-specific-related mortality due to immunotherapy alone which this case demonstrates the importance of vigilance and early detection for effective treatment and management. It highlights need for the oncological world and our colleagues in various other disciplines of healthcare to identify and mitigate the effects of immunotherapy which has become our hope in beating cancer.

scholarly journals Functional monovalency amplifies the pathogenicity of anti-MuSK IgG4 in myasthenia gravis

2021 ◽  
Vol 118 (13) ◽  
pp. e2020635118
Author(s):  
Dana L. E. Vergoossen ◽  
Jaap J. Plomp ◽  
Christoph Gstöttner ◽  
Yvonne E. Fillié-Grijpma ◽  
Roy Augustinus ◽  
...  
Keyword(s):  
Stochastic Process ◽  
Autoimmune Disease ◽  
Myasthenia Gravis ◽  
Muscle Weakness ◽  
Binding Sites ◽  
Antiinflammatory Activity ◽  
Autoimmune Response ◽  
Cross Link ◽  
Muscle Specific Kinase ◽  
Opposing Effects

Human immunoglobulin (Ig) G4 usually displays antiinflammatory activity, and observations of IgG4 autoantibodies causing severe autoimmune disorders are therefore poorly understood. In blood, IgG4 naturally engages in a stochastic process termed “Fab-arm exchange” in which unrelated IgG4s exchange half-molecules continuously. The resulting IgG4 antibodies are composed of two different binding sites, thereby acquiring monovalent binding and inability to cross-link for each antigen recognized. Here, we demonstrate that this process amplifies autoantibody pathogenicity in a classic IgG4-mediated autoimmune disease: muscle-specific kinase (MuSK) myasthenia gravis. In mice, monovalent anti-MuSK IgG4s caused rapid and severe myasthenic muscle weakness, whereas the same antibodies in their parental bivalent form were less potent or did not induce a phenotype. Mechanistically this could be explained by opposing effects on MuSK signaling. Isotype switching to IgG4 in an autoimmune response thereby may be a critical step in the development of disease. Our study establishes functional monovalency as a pathogenic mechanism in IgG4-mediated autoimmune disease and potentially other disorders.

scholarly journals Clinical features of neuromuscular disorders in patients with N-type voltage-gated calcium channel antibodies

2016 ◽  
Vol 26 (4) ◽  
Author(s):  
Andreas Totzeck ◽  
Petra Mummel ◽  
Oliver Kastrup ◽  
Tim Hagenacker
Keyword(s):  
Myasthenia Gravis ◽  
Calcium Channel ◽  
Muscle Weakness ◽  
Neuromuscular Disorders ◽  
Intravenous Immunoglobulins ◽  
Voltage Gated ◽  
Dropped Head Syndrome ◽  
Seronegative Myasthenia Gravis ◽  
Myasthenic Syndrome ◽  
Voltage Gated Calcium Channel

Neuromuscular junction disorders affect the pre- or postsynaptic nerve to muscle transmission due to autoimmune antibodies. Members of the group like myasthenia gravis and Lambert-Eaton syndrome have pathophysiologically distinct characteristics. However, in practice, distinction may be difficult. We present a series of three patients with a myasthenic syndrome, dropped-head syndrome, bulbar and respiratory muscle weakness and positive testing for anti-N-type voltage-gated calcium channel antibodies. In two cases anti-acetylcholin receptor antibodies were elevated, anti-P/Q-type voltage-gated calcium channel antibodies were negative. All patients initially responded to pyridostigmine with a non-response in the course of the disease. While one patient recovered well after treatment with intravenous immunoglobulins, 3,4-diaminopyridine, steroids and later on immunosuppression with mycophenolate mofetil, a second died after restriction of treatment due to unfavorable cancer diagnosis, the third patient declined treatment. Although new antibodies causing neuromuscular disorders were discovered, clinical distinction has not yet been made. Our patients showed features of pre- and postsynaptic myasthenic syndrome as well as severe dropped-head syndrome and bulbar and axial muscle weakness, but only anti-N-type voltage-gated calcium channel antibodies were positive. When administered, one patient benefited from 3,4-diaminopyridine. We suggest that this overlap-syndrome should be considered especially in patients with assumed seronegative myasthenia gravis and lack of improvement under standard therapy.

scholarly journals Myasthenic Crisis in an Elderly Patient with Positive Antibodies against Acetylcholine and Anti-MuSK, Successfully Treated with Noninvasive Mechanical Ventilation

2015 ◽  
Vol 2015 ◽  
pp. 1-4 ◽  
Author(s):  
José A. Fernández ◽  
Antonio Fernández-Valiñas ◽  
Daniel Hernández ◽  
Joel Orozco ◽  
Antonio Lugo
Keyword(s):  
Mechanical Ventilation ◽  
Myasthenia Gravis ◽  
Muscle Weakness ◽  
Noninvasive Ventilation ◽  
Ventilatory Support ◽  
Neurological Impairment ◽  
Respiratory Therapy ◽  
Myasthenic Crisis ◽  
Noninvasive Mechanical Ventilation ◽  
Myasthenic Patient

Myasthenia gravis is an autoimmune disease characterized by muscle weakness. Subjects with antibodies against acetylcholine usually have greater ocular symptoms, lower bulbar weakness, and fewer respiratory complications, compared to individuals with anti-MuSK antibodies. The presence of positivity to both types of antibodies in the same patient is uncommon, and the clinical behavior of these individuals is uncertain. A myasthenic crisis is characterized by respiratory and bulbar muscle weakness, causing acute respiratory failure which requires mechanical ventilatory support. We present the case of a 73-year-old man with a medical history of myasthenia gravis and positive antibody titers against acetylcholine and anti-MuSK, who sought for medical assessment because of respiratory tract infection symptoms, dysphagia, and generalized weakness. Initially, no respiratory distress was found. After 24 hours the patient showed respiratory deterioration and neurological impairment. Endotracheal intubation was rejected, so ventilatory support with noninvasive ventilation was started. The patient was supported by intense respiratory therapy, and infusion of immunoglobulin was initiated. The individual responded favorably, improving his general condition. Weaning from noninvasive mechanical ventilation was possible after six days. Our case illustrates that noninvasive ventilation, properly supported by intense respiratory therapy, can be a great option to avoid intubation in the myasthenic patient.

scholarly journals The Lambert-Eaton Myasthenic Syndrome — an Overview

2018 ◽  
Vol 02 (01) ◽  
pp. E40-E45
Author(s):  
Siegfried Kohler ◽  
Andreas Meisel
Keyword(s):  
Myasthenia Gravis ◽  
Case Reports ◽  
Compound Muscle Action Potential ◽  
Small Cell Lung Carcinoma ◽  
Immunosuppressive Treatment ◽  
Myasthenic Crisis ◽  
Cell Lung Carcinoma ◽  
Myasthenic Syndrome ◽  
Exercise Induced

AbstractThe Lambert Eaton myasthenic syndrome (LEMS) has a prevalence of around 5/100 0000 and is around 10–20 times rarer than myasthenia gravis (MG). Although LEMS does have a number of similarities to MG, there are important differences. The syndrome is characterized by a mostly proximally localised exercise induced muscle weakness that can lead to respiratory failure often accompanied by autonomous dysfunction. Disease symptoms are caused by autoantibodies directed against P/Q type voltage gated calcium channels (VGCC) that are expressed in the presynaptic motoric nerve terminals. The diagnosis of LEMS is based on the detection of the pathogenic anti-VGCC antibodies as well as the observation of an increment of at least 60% in the electrophysiological examination of an affected muscle. An increment is defined by an increase of the at rest reduced compound muscle action potential (CMAP) either after voluntary maximal innervation or after high frequent (≥20 Hz) stimulation. In almost one third LEMS is of paraneoplastic origin. Therefore an intensive tumor screening is necessary after diagnosis.There are some differences in the clinical presentation between paraneoplastic (pLEMS) and the exclusively autoimmune (aiLEMS) form of LEMS. With respect to this the DELTA-P-Score and the detection of SOX1-antibody are important. The most frequent tumor associated with LEMS is small cell lung carcinoma (SCLC). Therapy is based on the initial distinction between paraneoplastic and autoimmune ethiology. pLEMS necessitates therapy of underlying neoplasia. Usually, aiLEMS- as well as pLEMS patients respond well to 3,4 diaminopyridine (3,4 DAP) often augmented by pyridostigmine. Similar to treatment of myasthenia gravis long-term immunosuppressive treatment is usually required to control symptoms effectively. Myasthenic crisis in LEMS can be controlled by intensive care and immunoglobulins, plasmaphereses or immunoadsorption. Based on case reports more specific immunomodulatory treatment approaches such as the B-cell depleting therapeutic antibody rituximab should be considered in therapy refractory courses of LEMS. Long-term prognosis of autoimmune LEMS with respect to clinical stabilization with (pharmacological) remission is good, although in around 75% of patients significant reductions in quality of life remain. Prognosis of tumor-associated LEMS is largely determined by the tumor and its effective therapy. Curative treatment of the tumour as well as complete remission of pLEMS are possible.

scholarly journals Demyelinating disease in patients with myasthenia gravis

2008 ◽  
Vol 66 (1) ◽  
pp. 5-7 ◽  
Author(s):  
Denis Bernardi Bichuetti ◽  
Tatiane Martins de Barros ◽  
Enedina Maria Lobato Oliveira ◽  
Marcelo Annes ◽  
Alberto Alain Gabbai
Keyword(s):  
Autoimmune Disease ◽  
Autoimmune Diseases ◽  
Myasthenia Gravis ◽  
Muscle Weakness ◽  
Neuromyelitis Optica ◽  
Neuromuscular Transmission ◽  
Demyelinating Disease ◽  
Demyelinating Diseases

Myasthenia gravis (MG) is an autoimmune disease characterized by fluctuating muscle weakness, caused by impaired neuromuscular transmission. Patients with MG can present other autoimmune diseases in association, commonly hypo or hyperthyroidism. The association of MG to demyelinating disease is rare and has been described before. We report on three Brazilian patients with MG that presented distinct demyelinating diseases, two monophasic and one recurrent neuromyelitis optica, several years after the diagnosis of MG, and discuss their clinical courses.

scholarly journals Application of the Technique of Extracorporeal Membrane Oxygenation in a Patient With Respiratory Distress Syndrome Associated With Myasthenia Gravis

2021 ◽  
Vol 10 (2) ◽  
pp. 393-400
Author(s):  
N. M. Kruglyakov ◽  
D. G. Levitova ◽  
G. I. Bagzhanov ◽  
K. K. Gubarev ◽  
S. S. Ochkin ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Respiratory Failure ◽  
Extracorporeal Membrane Oxygenation ◽  
Myasthenia Gravis ◽  
Muscle Weakness ◽  
High Mortality ◽  
Respiratory Support ◽  
Myasthenic Crisis ◽  
Social Significance ◽  
Membrane Oxygenation

Myasthenia gravis is an autoimmune neuromuscular disease characterized by pathologically rapid fatigue of striated muscles [1]. The main symptom of myasthenia gravis is the presence of pathological muscle weakness with involvement of the ocular, bulbar and skeletal muscles in the pathological process. The provoking factors for the development of myasthenia gravis can be infectious diseases, surgery, drugs [2, 3]. The main danger is represented by myasthenic and cholinergic crises, which are characterized by a severe course and high mortality; therefore, the problems of treating myasthenia gravis are still of high medical and social significance. The prevalence of myasthenia gravis is 17.5–20.3 per 100 thousand population, and the number of patients is increasing by 5–10% annually [4, 5]. In recent years, there has been a steady increase in morbidity with an increase in age over 50 years [6, 7]. Myasthenia gravis is a serious disease with a high mortality rate of up to 30–40% [3]. There are difficulties in the early differential diagnosis of muscle weakness in patients with respiratory failure between myasthenia gravis, myasthenic syndrome and critical illness polyneuropathy. These difficulties and insufficient awareness of patients and doctors of various specialties about myasthenia gravis can lead to the choice of the wrong treatment tactics and the development of myasthenic crisis, which is manifested by respiratory failure, requiring respiratory support. The progression of respiratory failure against the background of myasthenic crisis may require the use of extracorporeal membrane oxygenation (ECMO).It is necessary to expand the differential diagnosis of muscle weakness in a patient during the period of resolution of respiratory failure, allowing to move away from compulsory respiratory support, termination of ECMO. 

scholarly journals Invasive medullary thymoma associated with myasthenia gravis: an unusual case

2000 ◽  
Vol 58 (4) ◽  
pp. 1110-1114 ◽  
Author(s):  
JORGE S. REIS FILHO ◽  
MARIA FERNANDA MILANEZI ◽  
CHRISTIANO G. MOREIRA ◽  
LINEU C. WERNECK ◽  
PAULO BOSCARDIN ◽  
...  
Keyword(s):  
Autoimmune Disease ◽  
Myasthenia Gravis ◽  
Unusual Case ◽  
Clinical Behavior ◽  
Histological Types ◽  
Morphological Heterogeneity ◽  
Myasthenic Syndrome ◽  
Frequent Variant ◽  
Clinical Associations ◽  
Hematological Abnormalities

Thymomas are tumors characterized by a remarkable morphological heterogeneity and variable clinical behavior. This tumor has unique clinical associations, most notably with hematological abnormalities and myasthenia gravis. According with the Müller-Hermelink criteria, there are significant differences between the histological types of thymomas and the association with myasthenia gravis. Among the different histological types, medullary thymoma is the least frequent variant associated with this autoimmune disease. In this report we describe a case of medullary thymoma presenting in a 71-year- old woman with a myasthenic syndrome.

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