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Neurology Jan 2021To update the 2016 formal consensus-based guidance for the management of myasthenia gravis (MG) based on the latest evidence in the literature. (Review)
Review
OBJECTIVE
To update the 2016 formal consensus-based guidance for the management of myasthenia gravis (MG) based on the latest evidence in the literature.
METHODS
In October 2013, the Myasthenia Gravis Foundation of America appointed a Task Force to develop treatment guidance for MG, and a panel of 15 international experts was convened. The RAND/UCLA appropriateness method was used to develop consensus recommendations pertaining to 7 treatment topics. In February 2019, the international panel was reconvened with the addition of one member to represent South America. All previous recommendations were reviewed for currency, and new consensus recommendations were developed on topics that required inclusion or updates based on the recent literature. Up to 3 rounds of anonymous e-mail votes were used to reach consensus, with modifications to recommendations between rounds based on the panel input. A simple majority vote (80% of panel members voting "yes") was used to approve minor changes in grammar and syntax to improve clarity.
RESULTS
The previous recommendations for thymectomy were updated. New recommendations were developed for the use of rituximab, eculizumab, and methotrexate as well as for the following topics: early immunosuppression in ocular MG and MG associated with immune checkpoint inhibitor treatment.
CONCLUSION
This updated formal consensus guidance of international MG experts, based on new evidence, provides recommendations to clinicians caring for patients with MG worldwide.
Topics: Antibodies, Monoclonal, Humanized; Consensus; Disease Management; Humans; Immune Checkpoint Inhibitors; Immunosuppressive Agents; Methotrexate; Myasthenia Gravis; Rituximab; Thymectomy
PubMed: 33144515
DOI: 10.1212/WNL.0000000000011124 -
Journal of Clinical Medicine Mar 2022Myasthenia 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... (Review)
Review
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.
PubMed: 35329925
DOI: 10.3390/jcm11061597 -
Cleveland Clinic Journal of Medicine Feb 2023Myasthenia gravis is a disorder of neuromuscular junction transmission, the result of antibodies against the post-synaptic aspect of the neuromuscular junction. Its... (Review)
Review
Myasthenia gravis is a disorder of neuromuscular junction transmission, the result of antibodies against the post-synaptic aspect of the neuromuscular junction. Its clinical hallmark is fatigable weakness of skeletal muscles, which tends to vary in location and severity among patients. It is treated with pyridostigmine, immunotherapy, and thymectomy. Treatment is often individualized according to disease severity, antibody status, comorbidities, and other factors. This review uses a question-and-answer format to provide up-to-date, high-yield, clinically relevant information on myasthenia gravis.
Topics: Humans; Myasthenia Gravis; Muscle, Skeletal; Muscle Weakness
PubMed: 36724914
DOI: 10.3949/ccjm.90a.22017 -
The New England Journal of Medicine Aug 2023The function of the thymus in human adults is unclear, and routine removal of the thymus is performed in a variety of surgical procedures. We hypothesized that the adult...
BACKGROUND
The function of the thymus in human adults is unclear, and routine removal of the thymus is performed in a variety of surgical procedures. We hypothesized that the adult thymus is needed to sustain immune competence and overall health.
METHODS
We evaluated the risk of death, cancer, and autoimmune disease among adult patients who had undergone thymectomy as compared with demographically matched controls who had undergone similar cardiothoracic surgery without thymectomy. T-cell production and plasma cytokine levels were also compared in a subgroup of patients.
RESULTS
After exclusions, 1420 patients who had undergone thymectomy and 6021 controls were included in the study; 1146 of the patients who had undergone thymectomy had a matched control and were included in the primary cohort. At 5 years after surgery, all-cause mortality was higher in the thymectomy group than in the control group (8.1% vs. 2.8%; relative risk, 2.9; 95% confidence interval [CI], 1.7 to 4.8), as was the risk of cancer (7.4% vs. 3.7%; relative risk, 2.0; 95% CI, 1.3 to 3.2). Although the risk of autoimmune disease did not differ substantially between the groups in the overall primary cohort (relative risk, 1.1; 95% CI, 0.8 to 1.4), a difference was found when patients with preoperative infection, cancer, or autoimmune disease were excluded from the analysis (12.3% vs. 7.9%; relative risk, 1.5; 95% CI, 1.02 to 2.2). In an analysis involving all patients with more than 5 years of follow-up (with or without a matched control), all-cause mortality was higher in the thymectomy group than in the general U.S. population (9.0% vs. 5.2%), as was mortality due to cancer (2.3% vs. 1.5%). In the subgroup of patients in whom T-cell production and plasma cytokine levels were measured (22 in the thymectomy group and 19 in the control group; mean follow-up, 14.2 postoperative years), those who had undergone thymectomy had less new production of CD4+ and CD8+ lymphocytes than controls (mean CD4+ signal joint T-cell receptor excision circle [sjTREC] count, 1451 vs. 526 per microgram of DNA [Pā=ā0.009]; mean CD8+ sjTREC count, 1466 vs. 447 per microgram of DNA [P<0.001]) and higher levels of proinflammatory cytokines in the blood.
CONCLUSIONS
In this study, all-cause mortality and the risk of cancer were higher among patients who had undergone thymectomy than among controls. Thymectomy also appeared be associated with an increased risk of autoimmune disease when patients with preoperative infection, cancer, or autoimmune disease were excluded from the analysis. (Funded by the Tracey and Craig A. Huff Harvard Stem Cell Institute Research Support Fund and others.).
Topics: Humans; Adult; Thymectomy; Thymus Gland; CD8-Positive T-Lymphocytes; Cytokines; Autoimmune Diseases
PubMed: 37530823
DOI: 10.1056/NEJMoa2302892 -
Clinical & Experimental Optometry Mar 2022Myasthenia gravis is a rare autoimmune disease characterised by autoantibodies preventing normal function of acetylcholine receptors at the post-synaptic membrane of the... (Review)
Review
Myasthenia gravis is a rare autoimmune disease characterised by autoantibodies preventing normal function of acetylcholine receptors at the post-synaptic membrane of the neuromuscular junction. This causes weakness of skeletal muscles that can be variable and fatigable, and often manifests as ptosis and/or diplopia, with 60% of patients demonstrating ocular features at onset, and thus may present initially to eye care practitioners. Approximately 15% of patients have ocular myasthenia gravis, where symptoms remain restricted to this distribution. The majority of patients have blocking antibodies against the acetylcholine receptor, but antibodies directed against other related targets account for a smaller proportion and are associated with specific phenotypes. Associations with both thymoma and with other autoimmune phenomena (particularly thyroid disease) can occur. Clinical examination can identify characteristic findings including fatigable ptosis and Cogan's lid twitch sign. Investigations to confirm the diagnosis include simple office-based procedures such as the ice test, and testing for serum autoantibodies, as well as electrophysiological testing such as repetitive nerve stimulation and single-fibre electromyography. The management of ocular myasthenia gravis is discussed, including non-pharmacological options, pyridostigmine, corticosteroids, other immunosuppressive agents, and thymectomy. The goals of management are to alleviate symptoms, and where possible prevent chronic disability or progression to generalised myasthenia gravis.
Topics: Diplopia; Humans; Immunosuppressive Agents; Myasthenia Gravis
PubMed: 35157811
DOI: 10.1080/08164622.2022.2029683 -
Frontiers in Neurology 2020Juvenile Myasthenia Gravis (JMG) is a rare disorder, defined as myasthenia gravis in children younger than 18 years of age. While clinical phenotypes are similar to... (Review)
Review
Juvenile Myasthenia Gravis (JMG) is a rare disorder, defined as myasthenia gravis in children younger than 18 years of age. While clinical phenotypes are similar to adults, there are a number of caveats that influence management: broader differential diagnoses; higher rates of spontaneous remission; and the need to initiate appropriate treatment early, to avoid the long-term physical and psychosocial morbidity. Current practice is taken from treatment guidelines for adult MG or individual experience, with considerable variability seen across centers. We discuss our approach to treating JMG, in a large specialist JMG service, and review currently available evidence and highlight potential areas for future research. First-line treatment of generalized JMG is symptomatic management with pyridostigmine, but early use of immunosuppression, where good control is not achieved is important. Oral prednisolone is used as first-line immunosuppression with appropriate prevention and monitoring of side effects. Second-line therapies including azathioprine and mycophenolate may be considered where there is: no response to steroids, inability to wean to a reasonable minimum effective dose or if side-effects are intolerable. Management of ocular JMG is similar, but requires close involvement of ophthalmology in young children to prevent amblyopia. Muscle-specific tyrosine kinase (MuSK)-JMG show a poorer response to pyridostigmine and anecdotal evidence suggests that rituximab should be considered as second-line immunosuppression. Thymectomy is indicated in any patient with a thymoma, and consideration should be given in acetylcholine receptor (AChR) positive JMG allowing time for spontaneous remission. The benefit is less clear in ocular JMG and is not advised in MuSK-JMG. Children experiencing a myasthenic crisis require urgent hospital admission with access to the intensive care unit. PLEX is preferred over IVIG due to rapid onset of action, but this needs to be balanced with feasibility in very young children. Key questions remain in the management of JMG: when to initiate both first- and second-line treatments, choosing between steroid-sparing agents, and determining the optimal dose and treatment duration. We feel that given the rarity of this disease, the establishment of national registries and collaboration across groups will be needed to address these issues and facilitate future drug trials in JMG.
PubMed: 32793107
DOI: 10.3389/fneur.2020.00743 -
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 -
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 -
Frontiers in Endocrinology 2023Secondary hyperparathyroidism (SHPT) is a major problem for patients with chronic kidney disease and can cause many complications, including osteodystrophy, fractures,... (Review)
Review
Secondary hyperparathyroidism (SHPT) is a major problem for patients with chronic kidney disease and can cause many complications, including osteodystrophy, fractures, and cardiovascular diseases. Treatment for SHPT has changed radically with the advent of calcimimetics; however, parathyroidectomy (PTx) remains one of the most important treatments. For successful PTx, removing all parathyroid glands (PTGs) without complications is essential to prevent persistent or recurrent SHPT. Preoperative imaging studies for the localization of PTGs, such as ultrasonography, computed tomography, and Tc-Sestamibi scintigraphy, and intraoperative evaluation methods to confirm the removal of all PTGs, including, intraoperative intact parathyroid hormone monitoring and frozen section diagnosis, are useful. Functional and anatomical preservation of the recurrent laryngeal nerves can be confirmed intraoperative nerve monitoring. Total or subtotal PTx with or without transcervical thymectomy and autotransplantation can also be performed. Appropriate operative methods for PTx should be selected according to the patients' need for kidney transplantation. In the case of persistent or recurrent SHPT after the initial PTx, localization of the causative PTGs with autotransplantation is challenging as causative PTGs can exist in the neck, mediastinum, or autotransplanted areas. Additionally, the efficacy and cost-effectiveness of calcimimetics and PTx are increasingly being discussed. In this review, medical and surgical treatments for SHPT are described.
Topics: Humans; Parathyroidectomy; Hyperparathyroidism, Secondary; Parathyroid Glands; Parathyroid Hormone; Neck
PubMed: 37152972
DOI: 10.3389/fendo.2023.1169793 -
The Primary Care Companion For CNS... May 2022eneralized myasthenia gravis (gMG) is a disease resulting from impaired neuromuscular transmission due to presence of antibodies that block acetylcholine receptors.... (Review)
Review
eneralized myasthenia gravis (gMG) is a disease resulting from impaired neuromuscular transmission due to presence of antibodies that block acetylcholine receptors. Autoantibodies to acetylcholine receptors directly impair the activity of ion channels that conduct nerve impulses, and cross-link acetylcholine receptors resulting in complement-mediated destruction, further worsening functional impairment and patient quality of life. Although current treatments for gMG include thymectomy, immunosuppressive therapies, intravenous immunoglobulins, and plasmapheresis, among other strategies, none of these treatments reduces all immunoglobulin G subfractions. However, with the novel neonatal Fc receptor antagonist efgartigimod, levels of all immunoglobulin G subfractions are reduced, addressing an important aspect of the underlying pathophysiology of gMG. Through this program, clinicians will consider novel mechanisms in gMG therapy, learn to counsel patients on the changing landscape of gMG therapies, and find ways to incorporate the latest efficacy and safety data into practice.
Topics: Autoantibodies; Humans; Immunoglobulin G; Infant, Newborn; Myasthenia Gravis; Quality of Life; Receptors, Cholinergic
PubMed: 35621832
DOI: 10.4088/PCC.AR21018WC2C