Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Randomised and controlled treatment studies of juvenile-onset myasthenia gravis have not been published. We therefore report our retrospective analysis of 79 patients with juvenile-onset myasthenia gravis observed for as long as 30 years. The mean age at onset was 13.7 years and median follow-up 7.7 years. The initial presentation was generalised disease in 90% and ocular disease in the remaining patients. Sixty-five patients (82%) were thymectomised. In 14 of these, treatment consisted of a combination of azathioprine (2-3 mg/kg), corticosteroids (prednisolone up to 60 mg for a maximum duration of 12 months with subsequent tapering) and acetylcholinesterase (AChE) inhibitors, and of azathioprine and AChE inhibitors in 27 patients. One patient received azathioprine and 22 AChE inhibitors only; in another no further medication was necessary. In the severely affected group (n = 16), plasmapheresis was performed additionally before thymectomy and continued for some time after the operation. Treatment was started between 1 and 14 months (mean 2.4 months) after the onset of myasthenic symptoms. No thymectomy was done in 14 patients, and immunosuppressive treatment and AChE inhibitors were given in 9 of these cases. One patient received azathioprine only; 4 patients received AChE inhibitors only. The histology of the thymus gland showed follicular hyperplasia in 89% of the 65 thymectomised patients and normal findings in the remainder. Remission occurred in 60% of patients who underwent thymectomy and in 29% of those who were not thymectomised. Hyperthyroidism (6 patients, 8%), diabetes mellitus (2 patients, 3%) and rheumatoid arthritis (2 patients, 3%) were the most frequent associated immune-mediated diseases. Epileptic seizures and neoplasia were coincident diseases in 2 (3%) and 3 (4%) patients, respectively. There were no deaths from thymectomy or from immunosupression. This open, retrospective analysis suggests that juvenile-onset myasthenia gravis can be treated satisfactorily in most patients by the use of thymectomy and/or immunosupressive medication.
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PMID:Outcome in juvenile-onset myasthenia gravis: a retrospective study with long-term follow-up of 79 patients. 930 59

Ocular myasthenia gravis is a not uncommon autoimmune disorder causing diplopia, ptosis, and weakness of lid closure. The predilection of myasthenia for the ocular muscles may be related to differences between limb and extraocular muscles in either physiological function or antigenicity. Clinically, ocular myasthenia can mimic any form of pupil-sparing ocular motility disorder. Dynamic abnormalities of myasthenic eye movements may reflect the primary hallmarks of the disease, which are fatigability and variability in strength, or secondary adaptive effects by the central nervous system. Tests to confirm the diagnosis include edrophonium challenge, repetitive nerve stimulation, single-fiber electromyography (EMG) of the frontalis, and assays for antibody directed against the acetylcholine receptor: all are less sensitive for ocular myasthenia than for generalized myasthenia. There is a higher incidence of other autoimmune conditions in myasthenia, notably thymoma and thyroid dysfunction. The differential diagnosis includes other diseases of the neuromuscular junction, such as Lambert-Eaton syndrome and botulism. Treatment consists of symptomatic use of acetylcholinesterase inhibitors and immunosuppression with steroids or azathioprine. Between 50 and 70% of patients with ocular myasthenia will eventually develop generalized disease: there is some retrospective data that steroids or azathioprine may reduce this by about 75%. The role of thymectomy in ocular myasthenia remains unclear.
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PMID:Ocular aspects of myasthenia gravis. 1087 73

The term seronegative myasthenia gravis (SNMG) refers to the generalized disease without detectable anti-acetylcholine receptor (anti-AChR) antibodies. In these patients, IgG antibodies against the muscle-specific kinase (MuSK) have been described, which reduced agrin-induced AChR clustering in vitro. We have assayed anti-MuSK antibodies in 78 patients with SNMG, who have been followed for many years in our Institution. Here we describe the clinical phenotype of the 37 patients whose results were positive on this assay. MG with anti-MuSK antibodies was characterized by a striking prevalence of female patients (eight men and 29 women). Age of onset ranged from 6 to 68 years, with 56.8% of patients presenting under 40 years of age. All these patients shared a similar pattern of muscle weakness, with prevalent involvement of cranial and bulbar muscles and a high frequency of respiratory crises; the involvement of limb muscles was comparatively less severe and inconsistent. Single-fibre-EMG confirmed the most sensitive examination in the EMG diagnosis of MuSK-positive disease, while, owing to weakness topography, repetitive nerve stimulation in limb muscles was diagnostic in 56.8% of cases. The effect of edrophonium (or neostigmine) injection was equivocal or negative in 11 of 37 patients (29.7%), and the response to oral pyridostigmine was even more unsatisfactory, ranging from mild benefit to overt intolerance. In thymectomized patients, thymus was normal for age or atrophied, and no benefit from surgery was noticed. Thirty-five of 37 patients were given immunosuppressive therapy and 22 received plasma-exchange. The course of the disease was often characterized by periodic exacerbation phases requiring hospitalization and even assisted ventilation; plasma-exchange produced marked improvement in these cases. At the end of the observation period, most patients, although improved, were still symptomatic, having developed permanent facial and pharyngeal weakness together with some atrophy of facial muscles. MuSK-negative disease was comparatively more heterogeneous. Most patients were affected with mild to moderate symptoms and responded well to pharmacological treatment; however, a few subjects in this group had severe refractory disease, poorly responsive to both acetylcholinesterase inhibitors and immunosuppressants.
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PMID:Clinical correlates with anti-MuSK antibodies in generalized seronegative myasthenia gravis. 1282 9

Myasthenia gravis (MG) is an autoimmune disease causing muscle weakness due to impaired transmission at the neuromuscular junction. MG or a MG-like condition may be triggered or exacerbated by several drugs used for treatment of other diseases. Drugs may interfere with the neuromuscular transmission through several mechanisms, either by affecting pre- or postsynaptic ion channels or by affecting acetylcholinesterase. Based on a literature search in PubMed and the authors' own clinical experiences, we provide an overview focusing on the most frequently used drugs that may exacerbate weakness in patients with MG. In our experience, symptomatic MG-patients who have a generalised disease are especially vulnerable to drug-induced exacerbations, while stable MG patients with few symptoms more seldom are. Nevertheless, patients with MG must receive treatment for co-existing conditions. It is important to be aware of a possible increase in muscle weakness when introducing a new drug. If the patient deteriorates, the new treatment must be withdrawn or the dose reduced.
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PMID:[Drugs that may trigger or exacerbate myasthenia gravis]. 2338 Nov 66

The detection of low density lipoprotein-4 (LRP4) antibodies in double seronegative (dSN) myasthenia gravis (MG) patients has provided new insights in the diagnosis and treatment of MG. However, there are limited data regarding the clinical presentation and treatment response in dSN MG patients with LRP4-antibodies. We present a case series of three Caucasian dSN MG patients with positive LRP4-antibodies sharing a common ethnic background that presented with isolated ocular symptoms (MGFA I). The demographic and clinical characteristics, the diagnostic work-up as well as the treatment response during a follow-up period of 12-24 months are described in detail. All patients were treated successfully with acetylcholinesterase inhibitors (AcheI) and prednisone with two exhibiting full remission of their symptoms, while the remaining exhibited mild residual diplopia. Notably, we documented no signs of generalized disease progression, while no patient required immunosuppressive treatment. In conclusion, the distinct clinical phenotype of our patients highlights the clinical relevance of screening for LRP4-antibodies in patients presenting with isolated ocular MG independent of age and gender, since it may lead to the timely diagnosis of MG and prompt initiation of effective therapy with ACheI and corticosteroids.
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PMID:Double seronegative myasthenia gravis with low density lipoprotein-4 (LRP4) antibodies presenting with isolated ocular symptoms. 2524 51

Myasthenia gravis (MG) is an autoimmune disease involving the neuromuscular junction. Autoantibodies to the acetylcholine receptor or, less frequently, to muscle-specific kinase, attack against the postsynaptic junctional proteins, resulting in fluctuating and variable weakness of muscles. Extraocular, levator palpebrae superioris, and orbicularis oculi muscles are particularly susceptible. The majority of patients with MG present with purely ocular symptoms including ptosis and diplopia initially. About half of these patients progress to generalized disease within 2 years. The prevalence of MG in Taiwan is 140 per million with male to female ratio of 0.7. The incidence rate is higher in the elderly. Several immune-related diseases such as lymphoid malignancy, diabetes, and thyroid diseases are associated with MG in the national population-based studies in Taiwan. Ice pack test, rest test, Tensilon/neostigmine test, circulating antibody measurement, and electrophysiological studies are useful diagnostic tools with variable sensitivity and specificity. For the patients with ocular MG, acetylcholinesterase inhibitors are usually the first-line treatment. Corticosteroids and immunosuppressant could provide better disease control and may reduce the risk of conversion to generalized form although there is still some controversy. A thymectomy is also beneficial for ocular MG, especially in refractory cases. The correction of ptosis and strabismus surgery could improve the visual outcome but should be performed only in stable disease.
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PMID:Update on ocular myasthenia gravis in Taiwan. 3003 84

When the diagnosis of myasthenia gravis (MG) has been secured, the aim of management should be prompt symptom control and the induction of remission or minimal manifestations. Symptom control, with acetylcholinesterase inhibitors such as pyridostigmine, is commonly employed. This may be sufficient in mild disease. There is no single universally accepted treatment regimen. Corticosteroids are the mainstay of immunosuppressive treatment in patients with more than mild MG to induce remission. Immunosuppressive therapies, such as azathioprine are prescribed in addition to but sometimes instead of corticosteroids when background comorbidities preclude or restrict the use of steroids. Rituximab has a role in refractory MG, while plasmapheresis and immunoglobulin therapy are commonly prescribed to treat MG crisis and in some cases of refractory MG. Data from the MGTX trial showed clear evidence that thymectomy is beneficial in patients with acetylcholine receptor (AChR) antibody positive generalized MG, up to the age of 65 years. Minimally invasive thymectomy surgery including robotic-assisted thymectomy surgery has further revolutionized thymectomy and the management of MG. Ocular MG is not life-threatening but can be significantly disabling when diplopia is persistent. There is evidence to support early treatment with corticosteroids when ocular motility is abnormal and fails to respond to symptomatic treatment. Treatment needs to be individualized in the older age-group depending on specific comorbidities. In the younger age-groups, particularly in women, consideration must be given to the potential teratogenicity of certain therapies. Novel therapies are being developed and trialed, including ones that inhibit complement-induced immunological pathways or interfere with antibody-recycling pathways. Fatigue is common in MG and should be duly identified from fatigable weakness and managed with a combination of physical therapy with or without psychological support. MG patients may also develop dysfunctional breathing and the necessary respiratory physiotherapy techniques need to be implemented to alleviate the patient's symptoms of dyspnoea. In this review, we discuss various facets of myasthenia management in adults with ocular and generalized disease, including some practical approaches and our personal opinions based on our experience.
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PMID:A Practical Approach to Managing Patients With Myasthenia Gravis-Opinions and a Review of the Literature. 3273 60