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Myasthenia Gravis: Clinical Manifestations, Epidemiology, Pathophysiology, Diagnosis, Current and Future Therapies

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Clinical Neurology".

Deadline for manuscript submissions: closed (31 May 2021) | Viewed by 137965

Special Issue Editor

Dr. Kourosh Rezania

E-Mail Website
Guest Editor
Department of Neurology, University of Chicago, Chicago, IL, USA
Interests: myasthenia gravis; amyotrophic lateral sclerosis; amyloidosis; neuropathy; myopathy

Special Issue Information

Dear Colleagues,

Myasthenia gravis (MG) is the most common disease of neuromuscular transmission. It is caused by production of antibodies against receptors in the neuromuscular junction. The incidence rate of MG is estimated to be 0.3–2.8 per 100,000, with an estimated prevalence rate of 5.35–35 per 100,000. While MG is often a mild disease localized to the extraocular muscles, it may result in weakness affecting the bulbar, limb, or respiratory muscles. MG is a treatable condition, but patients very often suffer from significant morbidity, though this rarely results in mortality. Treatment of MG consists of symptomatic management and immunomodulatory treatment. MG is currently the focus of extensive research, aimed both at unraveling the pathophysiological mechanisms and also the discovery of new therapeutic approaches that are more effective and have less adverse effects than the currently available treatments. In this issue, the authors will discuss the epidemiology, clinical manifestations, differential diagnosis, pathophysiology, diagnostic approach, current pharmacological treatment, and oncoming therapies, i.e., drugs in the pipeline.

Dr. Kourosh Rezania
Guest Editor

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Keywords

  • Myasthenia Gravis
  • AChR
  • MuSK
  • Immunotherapy
  • Prednisone
  • Eculizumab
  • Pyridostigmine
  • Tacrolimus
  • Rituximab
  • Complement
  • Neonatal FC receptor

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Published Papers (6 papers)

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Research

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13 pages, 738 KiB  
Article
Clinical Predictors of Prolonged Hospital Stay in Patients with Myasthenia Gravis: A Study Using Machine Learning Algorithms
by Che-Cheng Chang, Jiann-Horng Yeh, Yen-Ming Chen, Mao-Jhen Jhou and Chi-Jie Lu
J. Clin. Med. 2021, 10(19), 4393; https://doi.org/10.3390/jcm10194393 - 26 Sep 2021
Cited by 19 | Viewed by 3239
Abstract
Myasthenia gravis (MG) is an autoimmune disorder that causes muscle weakness. Although the management is well established, some patients are refractory and require prolonged hospitalization. Our study is aimed to identify the important factors that predict the duration of hospitalization in patients with [...] Read more.
Myasthenia gravis (MG) is an autoimmune disorder that causes muscle weakness. Although the management is well established, some patients are refractory and require prolonged hospitalization. Our study is aimed to identify the important factors that predict the duration of hospitalization in patients with MG by using machine learning methods. A total of 21 factors were chosen for machine learning analyses. We retrospectively reviewed the data of patients with MG who were admitted to hospital. Five machine learning methods, including stochastic gradient boosting (SGB), least absolute shrinkage and selection operator (Lasso), ridge regression (Ridge), eXtreme gradient boosting (XGboost), and gradient boosting with categorical features support (Catboost), were used to construct models for identify the important factors affecting the duration of hospital stay. A total of 232 data points of 204 hospitalized MG patients admitted were enrolled into the study. The MGFA classification, treatment of high-dose intravenous corticosteroid, age at admission, treatment with intravenous immunoglobulins, and thymoma were the top five significant variables affecting prolonged hospitalization. Our findings from machine learning will provide physicians with information to evaluate the potential risk of MG patients having prolonged hospital stay. The use of high-dose corticosteroids is associated with prolonged hospital stay and to be used cautiously in MG patients. Full article
(This article belongs to the Special Issue Myasthenia Gravis: Clinical Manifestations, Epidemiology, Pathophysiology, Diagnosis, Current and Future Therapies)
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14 pages, 970 KiB  
Article
Changes in Physical Fitness and Body Composition Associated with Physical Exercise in Patients with Myasthenia Gravis: A Longitudinal Prospective Study
by Che-Cheng Chang, Yen-Kung Chen, Hou-Chang Chiu and Jiann-Horng Yeh
J. Clin. Med. 2021, 10(17), 4031; https://doi.org/10.3390/jcm10174031 - 6 Sep 2021
Cited by 8 | Viewed by 4286
Abstract
There is a lack of guidelines for physical exercise in patients with myasthenia gravis (MG). A few pilot studies have shown that exercise can be safely applied to patients with MG. However, how physical exercise affects body composition, disease function, and disease severity [...] Read more.
There is a lack of guidelines for physical exercise in patients with myasthenia gravis (MG). A few pilot studies have shown that exercise can be safely applied to patients with MG. However, how physical exercise affects body composition, disease function, and disease severity remains unknown. In this prospective study, we enrolled 34 patients with MG with stable condition and evaluated the disease severity, physical fitness parameters, and body composition (measured using whole-body dual-energy X-ray absorptiometry (DXA)), before and after conducting a 24-week physical exercise regimen of aerobic and resistance strength training. The outcomes were measured by DXA, quantitative MG (QMG) score, quality of life score, handgrip strength and walking speed. During the training regimen, participants were free to decide how many exercise sessions per week and regularly reported their weekly exercise time. The physical exercise program was well tolerated by the participants, the parameters of the QMG score and handgrip strength improved, and participants’ body composition did not change significantly. The high exercise group experienced greater deterioration in muscle mass in the arms, but exhibited a greater improvement in forced vital capacity, walking speed, and symptom severity. The group with low QMG scores improved more in terms of physical fitness, including walking speed. These findings indicate that physical exercise is well tolerated by patients with MG, and is accompanied by improved muscular and physical functions. We propose that physical exercise is safe, effective, and appropriate for patients with well-regulated MG. Full article
(This article belongs to the Special Issue Myasthenia Gravis: Clinical Manifestations, Epidemiology, Pathophysiology, Diagnosis, Current and Future Therapies)
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Review

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23 pages, 1210 KiB  
Review
Current Treatment of Myasthenia Gravis
by Mohammed K. Alhaidar, Sumayyah Abumurad, Betty Soliven and Kourosh Rezania
J. Clin. Med. 2022, 11(6), 1597; https://doi.org/10.3390/jcm11061597 - 14 Mar 2022
Cited by 69 | Viewed by 30656
Abstract
Myasthenia gravis (MG) is the most extensively studied antibody-mediated disease in humans. Substantial progress has been made in the treatment of MG in the last century, resulting in a change of its natural course from a disease with poor prognosis with a high [...] Read more.
Myasthenia gravis (MG) is the most extensively studied antibody-mediated disease in humans. Substantial progress has been made in the treatment of MG in the last century, resulting in a change of its natural course from a disease with poor prognosis with a high mortality rate in the early 20th century to a treatable condition with a large proportion of patients attaining very good disease control. This review summarizes the current treatment options for MG, including non-immunosuppressive and immunosuppressive treatments, as well as thymectomy and targeted immunomodulatory drugs. Full article
(This article belongs to the Special Issue Myasthenia Gravis: Clinical Manifestations, Epidemiology, Pathophysiology, Diagnosis, Current and Future Therapies)
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17 pages, 1383 KiB  
Review
Myasthenia Gravis: Epidemiology, Pathophysiology and Clinical Manifestations
by Laura Dresser, Richard Wlodarski, Kourosh Rezania and Betty Soliven
J. Clin. Med. 2021, 10(11), 2235; https://doi.org/10.3390/jcm10112235 - 21 May 2021
Cited by 199 | Viewed by 53002
Abstract
Myasthenia gravis (MG) is an autoimmune neurological disorder characterized by defective transmission at the neuromuscular junction. The incidence of the disease is 4.1 to 30 cases per million person-years, and the prevalence rate ranges from 150 to 200 cases per million. MG is [...] Read more.
Myasthenia gravis (MG) is an autoimmune neurological disorder characterized by defective transmission at the neuromuscular junction. The incidence of the disease is 4.1 to 30 cases per million person-years, and the prevalence rate ranges from 150 to 200 cases per million. MG is considered a classic example of antibody-mediated autoimmune disease. Most patients with MG have autoantibodies against the acetylcholine receptors (AChRs). Less commonly identified autoantibodies include those targeted to muscle-specific kinase (MuSK), low-density lipoprotein receptor-related protein 4 (Lrp4), and agrin. These autoantibodies disrupt cholinergic transmission between nerve terminals and muscle fibers by causing downregulation, destruction, functional blocking of AChRs, or disrupting the clustering of AChRs in the postsynaptic membrane. The core clinical manifestation of MG is fatigable muscle weakness, which may affect ocular, bulbar, respiratory and limb muscles. Clinical manifestations vary according to the type of autoantibody, and whether a thymoma is present. Full article
(This article belongs to the Special Issue Myasthenia Gravis: Clinical Manifestations, Epidemiology, Pathophysiology, Diagnosis, Current and Future Therapies)
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16 pages, 7109 KiB  
Review
Diagnosis of Myasthenia Gravis
by Rossen T. Rousseff
J. Clin. Med. 2021, 10(8), 1736; https://doi.org/10.3390/jcm10081736 - 16 Apr 2021
Cited by 34 | Viewed by 19938
Abstract
The diagnosis of autoimmune Myasthenia Gravis (MG) remains clinical and rests on the history and physical findings of fatigable, fluctuating muscle weakness in a specific distribution. Ancillary bedside tests and laboratory methods help confirm the synaptic disorder, define its type and severity, classify [...] Read more.
The diagnosis of autoimmune Myasthenia Gravis (MG) remains clinical and rests on the history and physical findings of fatigable, fluctuating muscle weakness in a specific distribution. Ancillary bedside tests and laboratory methods help confirm the synaptic disorder, define its type and severity, classify MG according to the causative antibodies, and assess the effect of treatment objectively. We present an update on the tests used in the diagnosis and follow-up of MG and the suggested approach for their application. Full article
(This article belongs to the Special Issue Myasthenia Gravis: Clinical Manifestations, Epidemiology, Pathophysiology, Diagnosis, Current and Future Therapies)
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20 pages, 1255 KiB  
Review
Drugs That Induce or Cause Deterioration of Myasthenia Gravis: An Update
by Shuja Sheikh, Usman Alvi, Betty Soliven and Kourosh Rezania
J. Clin. Med. 2021, 10(7), 1537; https://doi.org/10.3390/jcm10071537 - 6 Apr 2021
Cited by 76 | Viewed by 23800
Abstract
Myasthenia gravis (MG) is an autoimmune neuromuscular disorder which is characterized by presence of antibodies against acetylcholine receptors (AChRs) or other proteins of the postsynaptic membrane resulting in damage to postsynaptic membrane, decreased number of AChRs or blocking of the receptors by autoantibodies. [...] Read more.
Myasthenia gravis (MG) is an autoimmune neuromuscular disorder which is characterized by presence of antibodies against acetylcholine receptors (AChRs) or other proteins of the postsynaptic membrane resulting in damage to postsynaptic membrane, decreased number of AChRs or blocking of the receptors by autoantibodies. A number of drugs such as immune checkpoint inhibitors, penicillamine, tyrosine kinase inhibitors and interferons may induce de novo MG by altering the immune homeostasis mechanisms which prevent emergence of autoimmune diseases such as MG. Other drugs, especially certain antibiotics, antiarrhythmics, anesthetics and neuromuscular blockers, have deleterious effects on neuromuscular transmission, resulting in increased weakness in MG or MG-like symptoms in patients who do not have MG, with the latter usually being under medical circumstances such as kidney failure. This review summarizes the drugs which can cause de novo MG, MG exacerbation or MG-like symptoms in nonmyasthenic patients. Full article
(This article belongs to the Special Issue Myasthenia Gravis: Clinical Manifestations, Epidemiology, Pathophysiology, Diagnosis, Current and Future Therapies)
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