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Cureus Dec 2023Myasthenia gravis (MG), a rare disease, is the most common neuromuscular junction problem. It's the quintessential autoimmune disease with ocular, bulbar, respiratory,... (Review)
Review
Myasthenia gravis (MG), a rare disease, is the most common neuromuscular junction problem. It's the quintessential autoimmune disease with ocular, bulbar, respiratory, axial, and limb muscles exhibiting a typical fatigable weakening due to the development of antibodies against the acetylcholine receptor (AChR). Infections, stress, surgeries, thymus gland anomalies, and pharmaceutical side effects can also cause it. Ocular symptoms are initially experienced by most of the sufferers. The majority of the sufferers will go through at least one episode of symptom exacerbation during their illness. The immune system in MG interferes with nerve-muscle communication, causing muscles to become weak and tired quickly. The actual cause is not yet known, but a problem in the thymus gland may be the cause. In a person suffering from this disease, the size of the thymus becomes larger than normal, which is also called thymic hyperplasia. It is more common for women to have early-onset MG (EOMG) than for males to have late-onset MG (LOMG). Merely clinical evidence, encompassing the patients' medical history and physical indications of fluctuating muscle weakness in a specific region, is utilized to diagnose MG. Complementary diagnostic procedures and lab techniques aid in confirming the synaptic dysfunction and characterizing its kind and degree. Early diagnosis and the availability of effective treatments have reduced the burden of severe impairment and high mortality previously associated with MG. Current immunomodulation-based therapies come with side effects brought on by persistent immune suppression. Improved knowledge of this relatively uncommon but curable condition is required among primary carers. The objective of this review is to provide information about MG and to help people recognize its symptoms and start treatment without panic so that the progression of this disease can be stopped and complications can be avoided.
PubMed: 38186498
DOI: 10.7759/cureus.50017 -
European Journal of Neurology Dec 2023Therapy for myasthenia gravis (MG) is undergoing a profound change, with new treatments being tested. These include complement inhibitors and neonatal Fc receptor (FcRn)... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND PURPOSE
Therapy for myasthenia gravis (MG) is undergoing a profound change, with new treatments being tested. These include complement inhibitors and neonatal Fc receptor (FcRn) blockers. The aim of this study was to perform a meta-analysis and network meta-analysis of randomized and placebo-controlled trials of innovative therapies in MG with available efficacy data.
METHODS
We assessed statistical heterogeneity across trials based on the Cochrane Q test and I values, and mean differences were pooled using the random-effects model. Treatment efficacy was assessed after 26 weeks of eculizumab and ravulizumab, 28 days of efgartigimod, 43 days of rozanolixizumab, 12 weeks of zilucoplan, and 16, 24 or 52 weeks of rituximab treatment.
RESULTS
We observed an overall mean Myasthenia Gravis-Activities of Daily Living scale (MG-ADL) score change of -2.17 points (95% confidence interval [CI] -2.67, -1.67; p < 0.001) as compared to placebo. No significant difference emerged between complement inhibitors and anti-FcRn treatment (p = 0.16). The change in Quantitative Myasthenia Gravis scale (QMG) score was -3.46 (95% CI -4.53, -2.39; p < 0.001), with a higher reduction with FcRns (-4.78 vs. -2.60; p < 0.001). Rituximab did not significantly improve the MG-ADL (-0.92 [95% CI -2.24, 0.39]; p = 0.17) or QMG scores (-1.9 [95% CI -3.97, 0.18]; p = 0.07). In the network meta-analysis, efgartigimod had the highest probability of being the best treatment, followed by rozanolixizumab.
CONCLUSION
Anti-complement and FcRn treatments both proved to be effective in MG patients, whereas rituximab did not show a significant benefit for patients. Within the limitations of this meta-analysis, including efficacy time points, FcRn treatments showed a greater effect on QMG score in the short term. Real-life studies with long-term measurements are needed to confirm our results.
Topics: Infant, Newborn; Humans; Rituximab; Network Meta-Analysis; Activities of Daily Living; Myasthenia Gravis; Complement Inactivating Agents; Therapies, Investigational
PubMed: 37204031
DOI: 10.1111/ene.15872 -
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 Functional Morphology and... Sep 2020Myasthenia gravis is a rare neuromuscular disorder characterized by muscle weakness and fatigue. This review analyzes the most recent evidence regarding the... (Review)
Review
Myasthenia gravis is a rare neuromuscular disorder characterized by muscle weakness and fatigue. This review analyzes the most recent evidence regarding the effectiveness and safety of different rehabilitative approaches to the disease. The review was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 365 articles were found in the main scientific databases. Applying the inclusion/exclusion criteria, 11 studies were admitted to the final phase of the review. Three different rehabilitative approaches were identified: physical training, respiratory training, and balance training. All rehabilitative modalities contributed to enhancing functional outcomes, reducing fatigue, and improving quality of life, but currently none can be recommended over another for the lack of cross-comparative studies. The included studies showed methodological quality from low to fair. Despite the range of rehabilitative interventions available, there is a lack of high-quality evidence. However, this review suggests that a multidisciplinary rehabilitation approach should be recommended to people with myasthenia gravis, and above all, for those with mild to moderate symptomatology.
PubMed: 33467286
DOI: 10.3390/jfmk5040071 -
Frontiers in Immunology 2019During the past years biologic agents (also termed biologicals or biologics) have become a crucial treatment option in immunological diseases. Numerous articles have...
During the past years biologic agents (also termed biologicals or biologics) have become a crucial treatment option in immunological diseases. Numerous articles have been published on biologicals, which complicates the decision making process on the use of the most appropriate biologic for a given immune-mediated disease. This systematic review is the first of a series of articles assessing the safety and efficacy of B cell-targeting biologics for the treatment of immune-mediated diseases. To evaluate rituximab's safety and efficacy for the treatment of immune-mediated disorders compared to placebo, conventional treatment, or other biologics. The PRISMA checklist guided the reporting of the data. We searched the PubMed database between 4 October 2016 and 26 July 2018 concentrating on immune-mediated disorders. The literature search identified 19,665 articles. After screening titles and abstracts against the inclusion and exclusion criteria and assessing full texts, 105 articles were finally included in a narrative synthesis. Rituximab is both safe and effective for the treatment of acquired angioedema with C1-inhibitor deficiency, ANCA-associated vasculitis, autoimmune hemolytic anemia, Behçet's disease, bullous pemphigoid, Castleman's disease, cryoglobulinemia, Goodpasture's disease, IgG4-related disease, immune thrombocytopenia, juvenile idiopathic arthritis, relapsing-remitting multiple sclerosis, myasthenia gravis, nephrotic syndrome, neuromyelitis optica, pemphigus, rheumatoid arthritis, spondyloarthropathy, and systemic sclerosis. Conversely, rituximab failed to show an effect for antiphospholipid syndrome, autoimmune hepatitis, IgA nephropathy, inflammatory myositis, primary-progressive multiple sclerosis, systemic lupus erythematosus, and ulcerative colitis. Finally, mixed results were reported for membranous nephropathy, primary Sjögren's syndrome and Graves' disease, therefore warranting better quality trials with larger patient numbers.
Topics: Animals; Antigens, CD20; B-Lymphocytes; Disease Progression; Humans; Immune System Diseases; Immunotherapy; Lymphocyte Depletion; Rituximab; Treatment Outcome
PubMed: 31555262
DOI: 10.3389/fimmu.2019.01990 -
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 -
The Oncologist Dec 2021The development of immune checkpoint inhibitors (ICIs) represents a paradigm shift in the treatment of cancers. Despite showing remarkable efficacy, these agents can be...
BACKGROUND
The development of immune checkpoint inhibitors (ICIs) represents a paradigm shift in the treatment of cancers. Despite showing remarkable efficacy, these agents can be associated with life-threatening immune-related adverse events. In recent years, several cases of myocarditis with myositis and/or myasthenia gravis overlap syndrome (IM3OS) have been reported. However, given the rarity, the clinical features and outcomes of these cases remain poorly understood. We, therefore, attempted to systematically review and summarize all cases of IM3OS reported in the literature.
MATERIALS AND METHODS
Studies reporting IM3OS were identified in Embase and MEDLINE. Only case reports and case series published in journals or presented at conferences were included. We conducted a systematic review according to the PRISMA Harms guidelines.
RESULTS
A total of 60 cases were eligible. The patients' median age was 71 years, and the majority (67%) were males; melanoma was the most common indication for ICIs (38%). The most-reported symptoms were fatigue (80%) and muscle weakness (78%). The median number of doses to the development of IM3OS was one. The average creatine kinase level was 9,645 IU/L. Cardiac arrhythmias occurred in 67% of patients, and 18% had depressed ejection fraction. Initial treatment consisted of immunosuppression with high-dose steroids and supportive therapies. Sixty percent of the patients died in hospital because of acute complications.
CONCLUSION
IM3OS can be associated with significant mortality and morbidity. Prospective studies are needed to understand the optimal approach to diagnose and manage these patients and to develop biomarkers to predict the occurrence and severity of this rare but serious condition.
IMPLICATIONS FOR PRACTICE
Clinicians should suspect coexisting myositis and/or myasthenia gravis in all patients with immune checkpoint inhibitor-induced myocarditis, given their propensity to occur together. Early recognition and prompt treatment with the help of a multidisciplinary team might help improve the outcomes of this life-threatening condition.
Topics: Aged; Humans; Immune Checkpoint Inhibitors; Myasthenia Gravis; Myocarditis; Myositis
PubMed: 34378270
DOI: 10.1002/onco.13931 -
Neurology Feb 2021Introduction and validation of a phenotypic classification of neurogenic dysphagia based on flexible endoscopic evaluation of swallowing (FEES).
OBJECTIVE
Introduction and validation of a phenotypic classification of neurogenic dysphagia based on flexible endoscopic evaluation of swallowing (FEES).
METHODS
A systematic literature review was conducted, searching MEDLINE from inception to May 2020 for FEES findings in neurologic diseases of interest. Based on a retrospective analysis of FEES videos in neurologic diseases and considering the results from the review, a classification of neurogenic dysphagia was developed distinguishing different phenotypes. The classification was validated using 1,012 randomly selected FEES videos of patients with various neurologic disorders. Chi-square tests were used to compare the distribution of dysphagia phenotypes between the underlying neurologic disorders.
RESULTS
A total of 159 articles were identified, of which 59 were included in the qualitative synthesis. Seven dysphagia phenotypes were identified: (1) "premature bolus spillage" and (2) "delayed swallowing reflex" occurred mainly in stroke, (3) "predominance of residue in the valleculae" was most common in Parkinson disease, (4) "predominance of residue in the piriform sinus" occurred only in myositis, motoneuron disease, and brainstem stroke, (5) "pharyngolaryngeal movement disorder" was found in atypical Parkinsonian syndromes and stroke, (6) "fatigable swallowing weakness" was common in myasthenia gravis, and (7) "complex disorder" with a heterogeneous dysphagia pattern was the leading mechanism in amyotrophic lateral sclerosis. The interrater reliability showed a strong agreement (kappa = 0.84).
CONCLUSION
Neurogenic dysphagia is not a symptom, but a multietiologic syndrome with different phenotypic patterns depending on the underlying disease. Dysphagia phenotypes can facilitate differential diagnosis in patients with dysphagia of unclear etiology.
Topics: Deglutition Disorders; Humans; Nervous System Diseases
PubMed: 33318164
DOI: 10.1212/WNL.0000000000011350 -
Pharmacological Reviews Apr 2021The complement system was discovered at the end of the 19th century as a heat-labile plasma component that "complemented" the antibodies in killing microbes, hence the...
The complement system was discovered at the end of the 19th century as a heat-labile plasma component that "complemented" the antibodies in killing microbes, hence the name "complement." Complement is also part of the innate immune system, protecting the host by recognition of pathogen-associated molecular patterns. However, complement is multifunctional far beyond infectious defense. It contributes to organ development, such as sculpting neuron synapses, promoting tissue regeneration and repair, and rapidly engaging and synergizing with a number of processes, including hemostasis leading to thromboinflammation. Complement is a double-edged sword. Although it usually protects the host, it may cause tissue damage when dysregulated or overactivated, such as in the systemic inflammatory reaction seen in trauma and sepsis and severe coronavirus disease 2019 (COVID-19). Damage-associated molecular patterns generated during ischemia-reperfusion injuries (myocardial infarction, stroke, and transplant dysfunction) and in chronic neurologic and rheumatic disease activate complement, thereby increasing damaging inflammation. Despite the long list of diseases with potential for ameliorating complement modulation, only a few rare diseases are approved for clinical treatment targeting complement. Those currently being efficiently treated include paroxysmal nocturnal hemoglobinuria, atypical hemolytic-uremic syndrome, myasthenia gravis, and neuromyelitis optica spectrum disorders. Rare diseases, unfortunately, preclude robust clinical trials. The increasing evidence for complement as a pathogenetic driver in many more common diseases suggests an opportunity for future complement therapy, which, however, requires robust clinical trials; one ongoing example is COVID-19 disease. The current review aims to discuss complement in disease pathogenesis and discuss future pharmacological strategies to treat these diseases with complement-targeted therapies. SIGNIFICANCE STATEMENT: The complement system is the host's defense friend by protecting it from invading pathogens, promoting tissue repair, and maintaining homeostasis. Complement is a double-edged sword, since when dysregulated or overactivated it becomes the host's enemy, leading to tissue damage, organ failure, and, in worst case, death. A number of acute and chronic diseases are candidates for pharmacological treatment to avoid complement-dependent damage, ranging from the well established treatment for rare diseases to possible future treatment of large patient groups like the pandemic coronavirus disease 2019.
Topics: COVID-19; Collectins; Complement Activating Enzymes; Complement C3; Complement Inactivating Agents; Complement System Proteins; Genetic Therapy; Humans; Inflammation Mediators; Lectins; Mannose-Binding Protein-Associated Serine Proteases; Pandemics; Rare Diseases; SARS-CoV-2; Synapses; Ficolins
PubMed: 33687995
DOI: 10.1124/pharmrev.120.000072 -
Autoimmunity Reviews Mar 2022Corticosteroids are the first-line treatment for several common autoimmune neurological diseases. Other therapeutic approaches, including intravenous immunoglobulin... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Corticosteroids are the first-line treatment for several common autoimmune neurological diseases. Other therapeutic approaches, including intravenous immunoglobulin (IVIg) and plasmapheresis, have shown mixed results in patient improvement.
OBJECTIVE
To compare the efficacy of IVIg administration with that of corticosteroids, plasmapheresis, and placebo in autoimmune neurological diseases like Guillain-Barré syndrome, myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, optic neuritis, and multiple sclerosis.
METHODS
A systematic review was performed on the databases PubMed, MEDLINE, Embase, and Cochrane. Controlled, randomized studies comparing the efficacy of IVIg with placebo, plasmapheresis, and/or glucocorticoid administration were selected. Only studies reporting the number of patients who improved after treatment were included, irrespective of language or publication year. In total, 23 reports were included in the meta-analysis study.
RESULTS
Our meta-analysis showed a beneficial effect of IVIg administration on patient improvement over placebo (OR = 2.79, CI [95%] = 1.40-5.55, P = 0.01). Meanwhile, IVIg administration showed virtually identical effects to plasmapheresis (OR = 0.83, CI [95%] = 0.45-1.55, P < 0.01). Finally, no significant differences were found in the efficacy of IVIg and glucocorticoid administration (OR = 0.98, Cl [95%] = 0.58-1.68, P = 0.13).
CONCLUSION
IVIg can be regarded as a viable therapeutic approach, either as a first- or second-line therapy, and as an adjuvant therapy for autoimmune neurological diseases.
Topics: Guillain-Barre Syndrome; Humans; Immunoglobulins, Intravenous; Myasthenia Gravis; Plasma Exchange; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
PubMed: 34920107
DOI: 10.1016/j.autrev.2021.103019