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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 -
Indian Journal of Ophthalmology Oct 2014Myasthenia gravis (MG) is a disease that affects the neuro-muscular junction resulting in classical symptoms of variable muscle weakness and fatigability. It is called... (Review)
Review
Myasthenia gravis (MG) is a disease that affects the neuro-muscular junction resulting in classical symptoms of variable muscle weakness and fatigability. It is called the great masquerader owing to its varied clinical presentations. Very often, a patient of MG may present to the ophthalmologist given that a large proportion of patients with systemic myasthenia have ocular involvement either at presentation or during the later course of the disease. The treatment of ocular MG involves both the neurologist and ophthalmologist. Thus, the aim of this review was to highlight the current diagnosis, investigations, and treatment of ocular MG.
Topics: Disease Management; Global Health; Humans; Morbidity; Myasthenia Gravis
PubMed: 25449931
DOI: 10.4103/0301-4738.145987 -
Journal For Immunotherapy of Cancer Nov 2019Myasthenia gravis (MG) is a rare but life-threatening adverse event of immune checkpoint inhibitors (ICI). Given the limited evidence, data from a large cohort of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Myasthenia gravis (MG) is a rare but life-threatening adverse event of immune checkpoint inhibitors (ICI). Given the limited evidence, data from a large cohort of patients is needed to aid in recognition and management of this fatal complication.
METHODS
We reviewed our institutional databases to identify patients who had cancer and MG in the setting of ICI. We systematically reviewed the literature through August 2018 to identify all similar reported patients. We collected data on clinical and diagnostic features, management, and outcomes of these cases.
RESULTS
Sixty-five patients were identified. Median age was 73 years; 42 (65%) were males, 31 (48%) had metastatic melanoma, and 13 (20%) had a preexisting MG before ICI initiation. Most patients received anti-PD-1 (82%). Sixty-three patients (97%) developed ICI-related MG (new onset or disease flare) after a median of 4 weeks (1 to 16 weeks) of ICI initiation. Twenty-four patients (37%) experienced concurrent myositis, and respiratory failure occurred in 29 (45%). ICI was discontinued in 61 patients (97%). Death was reported in 24 patients (38%); 15 (23%) due to MG complication. A better outcome was observed in patients who received intravenous immunoglobulin (IVIG) or plasmapheresis (PLEX) as first-line therapy than in those who received steroids alone (95% vs 63% improvement of MG symptoms, p = 0.011).
CONCLUSIONS
MG is a life-threatening adverse event of acute onset and rapid progression after ICI initiation. Early use of IVIG or PLEX, regardless of initial symptoms severity, may lead to better outcomes than steroids alone. Our data suggest the need to reassess the current recommendations for management of ICI-related MG until prospective longitudinal studies are conducted to establish the ideal management approach for these patients.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Immunological; Biomarkers; Disease Progression; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Molecular Targeted Therapy; Myasthenia Gravis; Neoplasms; Symptom Assessment
PubMed: 31753014
DOI: 10.1186/s40425-019-0774-y -
Journal of Neurology Aug 2016Myasthenia gravis (MG) is an autoimmune antibody-mediated disorder of neuromuscular synaptic transmission. The clinical hallmark of MG consists of fluctuating... (Review)
Review
Myasthenia gravis (MG) is an autoimmune antibody-mediated disorder of neuromuscular synaptic transmission. The clinical hallmark of MG consists of fluctuating fatigability and weakness affecting ocular, bulbar and (proximal) limb skeletal muscle groups. MG may either occur as an autoimmune disease with distinct immunogenetic characteristics or as a paraneoplastic syndrome associated with tumors of the thymus. Impairment of central thymic and peripheral self-tolerance mechanisms in both cases is thought to favor an autoimmune CD4(+) T cell-mediated B cell activation and synthesis of pathogenic high-affinity autoantibodies of either the IgG1 and 3 or IgG4 subclass. These autoantibodies bind to the nicotinic acetylcholine receptor (AchR) itself, or muscle-specific tyrosine-kinase (MuSK), lipoprotein receptor-related protein 4 (LRP4) and agrin involved in clustering of AchRs within the postsynaptic membrane and structural maintenance of the neuromuscular synapse. This results in disturbance of neuromuscular transmission and thus clinical manifestation of the disease. Emphasizing evidence from clinical trials, we provide an updated overview on immunopathogenesis, and derived current and future treatment strategies for MG divided into: (a) symptomatic treatments facilitating neuromuscular transmission, (b) antibody-depleting treatments, and
Topics: Disease Management; Germany; Humans; Myasthenia Gravis; Societies, Medical
PubMed: 26886206
DOI: 10.1007/s00415-016-8045-z -
Muscle & Nerve Feb 2018Myasthenia gravis (MG) is an archetypal autoimmune disease. The pathology is characterized by autoantibodies to the acetylcholine receptor (AChR) in most patients or to... (Review)
Review
Myasthenia gravis (MG) is an archetypal autoimmune disease. The pathology is characterized by autoantibodies to the acetylcholine receptor (AChR) in most patients or to muscle-specific tyrosine kinase (MuSK) in others and to a growing number of other postsynaptic proteins in smaller subsets. A decrease in the number of functional AChRs or functional interruption of the AChR within the muscle end plate of the neuromuscular junction is caused by pathogenic autoantibodies. Although the molecular immunology underpinning the pathology is well understood, much remains to be learned about the cellular immunology contributing to the production of autoantibodies. This Review documents research concerning the immunopathology of MG, bringing together evidence principally from human studies with an emphasis on the role of adaptive immunity and B cells in particular. Proposed mechanisms for autoimmunity, which take into account that different types of MG may incorporate divergent immunopathology, are offered. Muscle Nerve 57: 172-184, 2018.
Topics: B-Lymphocytes; Humans; Immunotherapy; Myasthenia Gravis; Neoplasms; T-Lymphocytes
PubMed: 28940642
DOI: 10.1002/mus.25973 -
Journal of Translational Medicine Dec 2021Myasthenia gravis is a neuromuscular autoimmune disorder characterized by weakness and disability in the voluntary muscles. There have been several preliminary studies... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Myasthenia gravis is a neuromuscular autoimmune disorder characterized by weakness and disability in the voluntary muscles. There have been several preliminary studies on the epidemiology of myasthenia gravis in different parts of the world and the effectiveness of common drugs in its treatment, but there has been no comprehensive study of the efficacy of common drugs in the treatment of myasthenia gravis. Therefore, this study aimed to determine the epidemiology of myasthenia gravis globally and the effectiveness of common drugs in its treatment using systematic review and meta-analysis.
METHODS
Research studies were extracted from IranDoc, MagIran, IranMedex, SID, ScienceDirect, Web of Sciences (WoS), ProQuest, Medline (PubMed), Scopus and Google Scholar based on Cochran's seven-step guidelines using existing keywords extracted in MeSH browser. The I test was used to calculate the heterogeneity of studies, and Begg and Mazumdar rank correlation tests were used to assess publication bias. Data were analyzed using Comprehensive Meta-Analysis software (Version 2).
RESULTS
In the search for descriptive studies based on the research question, 7374 articles were found. After deleting articles unrelated to the research question, finally, 63 articles with a sample size of 1,206,961,907 people were included in the meta-analysis. The prevalence of MG worldwide was estimated to be 12.4 people (95% CI 10.6-14.5) per 100,000 population. For analytical studies on the effectiveness of common myasthenia gravis drugs, 4672 articles were found initially, and after removing articles unrelated to the research question, finally, 20 articles with a sample size of 643 people in the drug group and 619 people in the placebo group were included in the study. As a result of the combination of studies, the difference between the mean QMGS score index after taking Mycophenolate and Immunoglobulin or plasma exchange drugs in the group of patients showed a significant decrease of 1.4 ± 0.77 and 0.62 ± 0.28, respectively (P < 0.01).
CONCLUSION
The results of systematic review of drug evaluation in patients with myasthenia gravis showed that Mycophenolate and Immunoglobulin or plasma exchange drugs have positive effects in the treatment of MG. It also represents the positive effect of immunoglobulin or plasma exchange on reducing SFEMG index and QMGS index and the positive effect of Mycophenolate in reducing MG-ADL index, SFEMG and Anti-AChR antibodies index. In addition, based on a meta-analysis of the random-effect model, the overall prevalence of MG in the world is 12.4 people per 100,000 population, which indicates the urgent need for attention to this disease for prevention and treatment.
Topics: Humans; Immunosuppressive Agents; Myasthenia Gravis; Plasma Exchange; Prevalence
PubMed: 34930325
DOI: 10.1186/s12967-021-03185-7 -
Neuromuscular Disorders : NMD Oct 2022Pyridostigmine is the most commonly used drug in the symptomatic treatment of myasthenia gravis (MG); however, research into its effectiveness and side effects is...
Pyridostigmine is the most commonly used drug in the symptomatic treatment of myasthenia gravis (MG); however, research into its effectiveness and side effects is scarce. The aim of this study was to assess the effectiveness, prevalence of side effects and net benefit of pyridostigmine. All MG patients participating in the Dutch-Belgian myasthenia patient registry were included. A dynamic online questionnaire was developed to assess the effectiveness, side effects and net benefit of pyridostigmine. Out of 642 invited patients, 410 patients (64%) fully completed the questionnaire; 61% reported that they currently used pyridostigmine, 36% had discontinued pyridostigmine and 2% reported to never have used pyridostigmine. Patients reported a median effectiveness of 60, IQR 28-78 and net benefit of 65, IQR 45-84. Of all patients currently using pyridostigmine, 91% reported side effects (vs. 55% in the control group). Most frequently reported side effects were flatulence, urinary urgency, muscle cramps, blurred vision and hyperhidrosis. In the group of patients who discontinued pyridostigmine, side effects were the reason for discontinuation in 26%. Diarrhea, abdominal cramps and muscle twitching were the most frequently cited reasons to discontinue pyridostigmine. These results can be used to guide shared decision making prior to starting symptomatic treatment for MG.
Topics: Humans; Pyridostigmine Bromide; Cross-Sectional Studies; Myasthenia Gravis; Muscle Weakness
PubMed: 36184373
DOI: 10.1016/j.nmd.2022.09.002 -
Neuromuscular Disorders : NMD Feb 2020Myasthenia gravis is an autoimmune disease characterized by dysfunction of the neuromuscular junction. Current treatment is based on lifestyle advice, symptomatic... (Review)
Review
Myasthenia gravis is an autoimmune disease characterized by dysfunction of the neuromuscular junction. Current treatment is based on lifestyle advice, symptomatic treatment, immunosuppressive drugs and thymectomy. Corticosteroids remain the cornerstone of treatment beside symptomatic medication due to their low cost, wide availability and fast mode of action. However, long term steroid use carries substantial risks of severe adverse side effects. Therefore, non-steroidal immunosuppressive drugs are commonly added to the treatment. Unfortunately, they have a delayed-onset effect and evidence of their efficacy appears to be difficult to obtain. Several trials using drugs that have had clear positive results in other immunological disorders have failed in myasthenia. This failure may in part be related to difficulties in the design of clinical trial for myasthenia, which has a fluctuating disease course involving weakness that may be difficult to assess quantitively. This problem is exacerbated by the tendency of most clinical trials to select patients with a stable, but severe disease. Future trials should: select patients with weakness and fatigability that is completely explained by their myasthenia gravis, use a design that avoids the exclusion of patients with recent changes in medication, and explore the possibilities to completely avoid the use of corticosteroids.
Topics: Adrenal Cortex Hormones; Antibodies, Monoclonal; Exercise Therapy; Humans; Immunosuppressive Agents; Myasthenia Gravis; Proteasome Inhibitors; Thymectomy
PubMed: 32007304
DOI: 10.1016/j.nmd.2019.12.003 -
Medicina 2019Juvenile myasthenia gravis is a rare autoimmune disease, which has made it difficult to collect data from prospective randomized controlled trials to evaluate the...
Juvenile myasthenia gravis is a rare autoimmune disease, which has made it difficult to collect data from prospective randomized controlled trials to evaluate the efficacy and results of different treatments. Although there are differences between the juvenile myasthenia gravis and that of the adult, the data provided by some researches in adults in the treatment of juvenile myasthenia gravis have been used. The different therapeutic options will be evaluated, with the different evidences that sustain it and a treatment algorithm will be elaborated keeping always in mind that each patient offers us different challenges.
Topics: Child; Cholinesterase Inhibitors; Humans; Immunosuppressive Agents; Myasthenia Gravis; Steroids; Thymectomy
PubMed: 31603848
DOI: No ID Found -
Journal of Neuroinflammation Apr 2022Myasthenic crisis (MC) and disease exacerbation in myasthenia gravis (MG) are associated with significant lethality and continue to impose a high disease burden on... (Observational Study)
Observational Study
BACKGROUND
Myasthenic crisis (MC) and disease exacerbation in myasthenia gravis (MG) are associated with significant lethality and continue to impose a high disease burden on affected patients. Therefore, we sought to determine potential predictors for MC and exacerbation as well as to identify factors affecting outcome.
METHODS
We examined a retrospective, observational cohort study of patients diagnosed with MG between 2000 and 2021 with a mean follow-up of 62.6 months after diagnosis from eight tertiary hospitals in Germany. A multivariate Cox regression model with follow-up duration as the time variable was used to determine independent risk factors for MC and disease exacerbation.
RESULTS
815 patients diagnosed with MG according to national guidelines were included. Disease severity at diagnosis (quantitative MG score or Myasthenia Gravis Foundation of America class), the presence of thymoma and anti-muscle specific tyrosine kinase-antibodies were independent predictors of MC or disease exacerbation. Patients with minimal manifestation status 12 months after diagnosis had a lower risk of MC and disease exacerbation than those without. The timespan between diagnosis and the start of immunosuppressive therapy did not affect risk. Patients with a worse outcome of MC were older, had higher MGFA class before MC and at admission, and had lower vital capacity before and at admission. The number of comorbidities, requirement for intubation, prolonged mechanical ventilation, and MC triggered by infection were associated with worse outcome. No differences between outcomes were observed comparing treatments with IVIG (intravenous immunoglobulin) vs. plasma exchange vs. IVIG together with plasma exchange.
CONCLUSIONS
MC and disease exacerbations inflict a substantial burden of disease on MG patients. Disease severity at diagnosis and antibody status predicted the occurrence of MC and disease exacerbation. Intensified monitoring with emphasis on the prevention of infectious complications could be of value to prevent uncontrolled disease in MG patients.
Topics: Disease Progression; Humans; Immunoglobulins, Intravenous; Myasthenia Gravis; Retrospective Studies; Risk Factors
PubMed: 35413850
DOI: 10.1186/s12974-022-02448-4