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Neurological Sciences : Official... Apr 2021In the last years, significant advances have improved the knowledge of myasthenia gravis (MG) immunopathogenesis and have enabled to realize new molecules with a... (Review)
Review
In the last years, significant advances have improved the knowledge of myasthenia gravis (MG) immunopathogenesis and have enabled to realize new molecules with a selective action targeting compounds of the immunological system. This review discusses emerging treatments for MG, including complement inhibitors, neonatal Fc receptor targeting agents, and B cell interfering drugs, focusing on benefit and danger. In the second section of the review, several related adverse events of immunotherapy, including MGonset, are debated.
Topics: B-Lymphocytes; Humans; Immunologic Factors; Immunotherapy; Infant, Newborn; Myasthenia Gravis
PubMed: 33543421
DOI: 10.1007/s10072-021-05077-6 -
Neuromuscular Disorders : NMD May 2024Azathioprine is recommended as the first-line steroid-sparing immunosuppressive agent for myasthenia gravis. Mycophenolate and methotrexate are often considered as...
Azathioprine is recommended as the first-line steroid-sparing immunosuppressive agent for myasthenia gravis. Mycophenolate and methotrexate are often considered as second-line choices despite widespread consensus on their efficacy. We aimed to gather real-world data comparing the tolerability and reasons for discontinuation for these agents, by performing a national United Kingdom survey of side effects and reasons for discontinuation of immunosuppressants in myasthenia gravis. Of 235 patients, 166 had taken azathioprine, 102 mycophenolate, and 40 methotrexate. The most common side effects for each agent were liver dysfunction for azathioprine (23 %), diarrhoea for mycophenolate (14 %), and fatigue for methotrexate (18 %). Women were generally more likely to experience side effects of immunosuppressants. Azathioprine was significantly more likely to be discontinued than mycophenolate and methotrexate due to side effects. There was no significant difference in treatment cessation due to lack of efficacy. This study highlights the significant side-effect burden of treatment for myasthenia gravis. Mechanisms to reduce azathioprine toxicity should be utilised, however mycophenolate and methotrexate appear to be good treatment choices if teratogenicity is not a concern. Women are disadvantaged due to higher frequency of side effects and considerations around pregnancy and breastfeeding. Treatments with improved tolerability are needed.
Topics: Humans; Myasthenia Gravis; Methotrexate; Female; Mycophenolic Acid; Azathioprine; Immunosuppressive Agents; Male; Middle Aged; Adult; Aged; United Kingdom
PubMed: 38626662
DOI: 10.1016/j.nmd.2024.03.010 -
CNS Neuroscience & Therapeutics Feb 2024This comprehensive review aimed to compile cases of patients with thymoma diagnosed with both autoimmune encephalitis (AE) and myasthenia gravis (MG), and describe their... (Review)
Review
OBJECTIVES
This comprehensive review aimed to compile cases of patients with thymoma diagnosed with both autoimmune encephalitis (AE) and myasthenia gravis (MG), and describe their clinical characteristics.
METHODS
Clinical records of 3 AE patients in the first affiliated hospital of Sun Yat-sen University were reviewed. All of them were diagnosed with AE between 1 November 2021 and 1 March 2022, and clinical evidence about thymoma and MG was found. All published case reports were searched for comprehensive literature from January 1990 to June 2022.
RESULTS
A total of 18 cases diagnosed with thymoma-associated autoimmune encephalitis (TAAE) and thymoma-associated myasthenia gravis (TAMG) were included in this complication, wherein 3 cases were in the first affiliated hospital of Sun Yat-sen University and the other 15 were published case reports. 5/18 patients had alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antibody (AMPAR-Ab) in their serum and cerebrospinal fluid (CSF). All of them had positive anti-acetylcholine receptor antibody (AChR-Ab). And 12/18 patients showed a positive response to thymectomy and immunotherapy. Besides, thymoma recurrences were detected because of AE onset. And the shortest interval between operation and AE onset was 2 years in patients with thymoma recurrence.
CONCLUSIONS
There was no significant difference in the clinical manifestations between these patients and others with only TAMG or TAAE. TAAE was commonly associated with AMPAR2-Ab. Significantly, AE more commonly heralded thymoma recurrences than MG onset. And the intervals of thymectomy and MG or AE onset had different meanings for thymoma recurrence and prognoses of patients.
Topics: Humans; Thymoma; Thymus Neoplasms; Myasthenia Gravis; Encephalitis; Hashimoto Disease
PubMed: 38421083
DOI: 10.1111/cns.14568 -
Neurological Sciences : Official... Apr 2022Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction that can be exacerbated by many viral infections, including COVID-19. The management of MG... (Review)
Review
BACKGROUND
Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction that can be exacerbated by many viral infections, including COVID-19. The management of MG exacerbations is challenging in this scenario. We report 8 cases of MG exacerbation or myasthenic crisis associated with COVID-19 and discuss prognosis and treatment based on a literature review.
RESULTS
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.
DISCUSSION
This is the largest case series of MG exacerbation or myasthenic crisis due to COVID-19 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.
Topics: COVID-19; Female; Humans; Middle Aged; Myasthenia Gravis; Plasma Exchange; SARS-CoV-2
PubMed: 35039987
DOI: 10.1007/s10072-021-05823-w -
Frontiers in Pediatrics 2022Myasthenia gravis is an organ-specific autoimmune disease. Currently there is no universal guidelines for childhood-onset myasthenia gravis, therefore, treatment...
Myasthenia gravis is an organ-specific autoimmune disease. Currently there is no universal guidelines for childhood-onset myasthenia gravis, therefore, treatment strategies are usually based on the guidelines from adult myasthenia gravis patients. In order to contribute in the process of the development of the universal childhood-onset myasthenia gravis guideline, we have summarized the clinical characteristics, treatment strategies, outcome and the related predictors of childhood-onset myasthenia gravis. We recruited 343 childhood-onset myasthenia gravis cases who were followed up at the Department of Pediatrics, Xiangya Hospital from June, 2010 to December, 2019. The data about clinical characteristics, treatments and outcome were collected and analyzed. Among of the 343 cases, 164 cases were followed up for longer than 2 years, of whom 142 still remained with ocular myasthenia gravis at the endpoint. About the treatments, 27 cases (27/164) accepted pyridostigmine only while the rest accepted glucocorticoid and/or other immunosuppressants. At the endpoint, the proportion of optimal outcome was 66.2% in the group remaining with ocular myasthenia gravis and 31.8% in the generalized myasthenia gravis group. Multivariate logistic regression analysis revealed that generalized myasthenia gravis type and positive status of antibodies against acetylcholine receptors were the independent risk factors for poor outcome. In conclusion, our childhood-onset myasthenia gravis patients present mainly as ocular myasthenia gravis, adequate immunotherapy improve the long-term outcome, and generalized myasthenia gravis phenotype as well as positive status of antibodies against acetylcholine receptors relate to poor outcome.
PubMed: 36245736
DOI: 10.3389/fped.2022.996213 -
Neurology India 2020Myasthenic crisis (MC) is mainly managed by invasive ventilation (IV) which is associated with prolonged intubation and ventilation and respiratory complication.
BACKGROUND
Myasthenic crisis (MC) is mainly managed by invasive ventilation (IV) which is associated with prolonged intubation and ventilation and respiratory complication.
AIM
To report the characteristics of patients who can be managed by noninvasive ventilation (NIV) and also predictors of NIV in myasthenia gravis (MG).
PATIENTS AND METHODS
In a retrospective study at tertiary care hospital in India during 2013-2015, patients with MG were evaluated. MG was diagnosed by clinical, repetitive nerve stimulation, and acetylcholine receptor antibodies. Patients were intubated based on arterial blood gas criteria. Demographic variables, Myasthenia Gravis Foundation of America (MGFA) score, and clinical examination were done. NIV success was defined if patient did not need mechanical ventilation (MV) in the management or for 72 h after extubation and was considered unsuccessful if patients required MV during this period.
RESULTS
Twenty three out of 68 MG patients had MC, 16 patients were given NIV, and 16 IV. Median intensive care unit stay was 18 (4-94) days. Predictors of crisis were infection, bulbar weakness, MGFA > 2b, and history of crisis. NIV was the only respiratory support in 7 patients and reintubation was prevented in 3 patients. NIV failed in 9 patients. Comparison of NIV success and failure did not reveal any difference.
CONCLUSION
With NIV, intubation was prevented in 7 and reintubation in 3 patients. NIV has lower incidence of complications. NIV should be tried in patients with impending MC.
Topics: Humans; India; Intensive Care Units; Myasthenia Gravis; Noninvasive Ventilation; Respiration, Artificial; Respiratory Insufficiency; Retrospective Studies
PubMed: 32643679
DOI: 10.4103/0028-3886.289001 -
Neurology and Therapy Oct 2023This article provides a summary of a previously published paper: Terminal Complement Inhibitor Ravulizumab in Generalized Myasthenia Gravis. The paper reported the...
This article provides a summary of a previously published paper: Terminal Complement Inhibitor Ravulizumab in Generalized Myasthenia Gravis. The paper reported the results of the CHAMPION-MG trial which investigated the drug ravulizumab in the rare disease, myasthenia gravis. Terminal Complement Inhibitor Ravulizumab in Generalized Myasthenia Gravis (MP4 594600 KB).
PubMed: 37351816
DOI: 10.1007/s40120-023-00514-4 -
Frontiers in Neurology 2022Myasthenia gravis (MG) appears to have a similar incidence among adult populations worldwide. However, epidemiological and phenotypic differences have been noted among... (Review)
Review
Myasthenia gravis (MG) appears to have a similar incidence among adult populations worldwide. However, epidemiological and phenotypic differences have been noted among children and juveniles with MG. We reviewed the literature on childhood- and juvenile-onset MG among different populations, with the focus on ocular involvement, antibody profiles, the genetic susceptibility to juvenile MG phenotypes, the use of immune treatments, and the reported responses of extraocular muscles to therapies. Although epidemiological studies used different methodologies, reports from Asia, compared to Europe, showed more than two-fold higher proportions of prepubertal onset (before 12 years) vs. postpubertal-onset juveniles with MG. Compared to European children, ocular MG was 4-fold more frequent among Asian children, and 2-3-fold more frequent among children with African ancestry both in prepubertal and postpubertal ages at onset. These results suggest genetic influences. In Asia, and appeared overrepresented in children with ocular MG. In Europe, children with MG had a significantly higher rate of transforming from ocular to generalized disease and with an overrepresentation of . Although treatment regimens vary widely and the responses to immune therapies of the ocular muscles involved in MG were generally poorly described, there were indications that earlier use of steroid therapy may have better outcomes. Reports of treatment-resistant ophthalmoplegia may be more frequent in African and Asian juvenile MG cohorts compared to Europeans. Genetic and muscle gene expression studies point to dysregulated muscle atrophy signaling and mitochondrial metabolism pathways as pathogenetic mechanisms underpinning treatment-resistant ophthalmoplegia in susceptible individuals. In conclusion, phenotypic differences in juveniles with ocular manifestations of MG were evident in different populations suggesting pathogenetic influences. Treatment responses in MG-associated ocular disease should attract more careful descriptive reports. In MG, extraocular muscles may be vulnerable to critical periods of poor force generation and certain individuals may be particularly susceptible to developing treatment-resistant ophthalmoplegia. The development of prognostic biomarkers to identify these susceptible individuals is an unmet need.
PubMed: 35280301
DOI: 10.3389/fneur.2022.834212 -
Frontiers in Neurology 2020Timely and accurate diagnosis of myasthenia gravis, particularly in patients with fluctuating, isolated ocular involvement, remains challenging. Serological antibody... (Review)
Review
Timely and accurate diagnosis of myasthenia gravis, particularly in patients with fluctuating, isolated ocular involvement, remains challenging. Serological antibody testing and repetitive nerve stimulation of peripheral muscles usually have low sensitivity in these patients. Edrophonium testing may cause adverse events, single-fiber electromyography (SFEMG) is time-consuming and both tests are often unavailable outside specialized institutions. Repetitive ocular vestibular evoked myogenic potential (roVEMP) stimulation has recently been introduced to facilitate the diagnosis of myasthenia gravis. Similar to repetitive nerve stimulation, roVEMPs detect muscle decrements with the benefit of being non-invasive and allowing for direct measurement of the extraocular muscles. This review summarizes the clinical evidence of the diagnostic value of roVEMP for myasthenia. Prospective clinical trials have demonstrated high sensitivity and specificity. RoVEMPs are of particular interest in challenging myasthenia subgroups with isolated ocular involvement, negative serology, and/or negative conventional electrophysiological results. Optimal roVEMP repetition rates of 20-30 Hz have been identified. This promising novel diagnostic tool merits further attention and investigation to establish its value as a clinical test for myasthenia.
PubMed: 32903498
DOI: 10.3389/fneur.2020.00861