Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine the potential importance of an immune response directed against the acetylcholine receptor in myasthenia gravis, we studied cell-mediated immunity to receptor as measured by lymphocyte stimulation in 21 myasthenic patients and 21 controls, including five with amyotrophic lateral sclerosis. The mean (+/- S.E.M.) stimulation index was 5.3 +/- 1.3 for patients and 1.2 +/- 0.3 for controls (P less than 0.005). Fourteen patients had indexes greater than 2.0 (nine of 11 males, five of 10 females, 10 of 11 elderly patients, and five of six with thymoma). Stimulation index correlated with disease activity (rs = 0.71, P less than 0.01). Peripheral blood lymphocytes from one of three young female myasthenic patients responded to autologous thymocytes but not to receptor; peripheral blood lymphocytes from the other two responded to receptor but not to autologous thymocytes. Our findings are further evidence that autoimmunity to the acetylcholine receptor plays a central part in myasthenia gravis.
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PMID:Cellular immunity in myasthenia gravis. Response to purified acetylcholine receptor and autologous thymocytes. 12 5

Acetylcholine receptor (AChR) binding and AChR modulating antibodies were found with approximately the same frequency (86%) in 349 patients with myasthenia gravis (MG). However, the total yield of positive serological results was significantly improved (90%) by assaying AChR modulating antibodies when AChR binding antibodies were not detected, because in 27 patients (8%) only one of the two tests was positive. The immunoprecipitation test for AChR blocking antibodies yielded fewer positive results (52%), but there was a significant correlation between the degree of AChR blockade and generalization of muscle weakness. In no patient was this the only positive test, because the test for AChR modulating antibodies in this study detected both AChR blocking and modulating antibodies. Human muscle AChR was used as antigen in all tests. False positive results were rare and were attributed to unexplained antibodies to 125I-alpha-Bgt (AChR binding antibody assay) and recent general anesthesia using muscle relaxants (AChR blocking and AChR modulating antibody assays). Unexplained positive results, documented previously in 5% of patients with the Lambert-Eaton myasthenic syndrome and amyotrophic lateral sclerosis (ALS), were found in this study in two of 22 patients with ALS, but in none of 427 patients with miscellaneous neurological diseases. Patients with severe generalized MG and/or thymoma tended to have higher titers of AChR binding antibodies and greater AChR modulating antibody activity. However, some patients with severe muscle weakness had low titers of antibodies, and some patients in remission or with only ocular manifestations had high titers. These seemingly paradoxical results reflect heterogeneity in the specificities, affinities, and isotypes of anti-AChR antibodies. To effect pathogenicity, antibodies must have access in vivo to extracellular antigenic sites on the AChR. One would anticipate that antibodies with greatest pathophysiological potential would be of an IgG with greatest pathophysiological potential would be of an IgG subclass that activates complement, or of a specificity that competes for acetylcholine's binding site on the receptor or readily cross-links two AChR molecules to trigger receptor modulation (e.g., by binding to sites on the duplicated alpha-subunit). In patients with suspected MG who lack serological evidence of anti-AChR antibodies, motor endplate biopsy is required for microelectrophysiological, immunochemical, and ultrastructural studies to establish with certainty whether or not the condition is acquired MG.
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PMID:Clinical correlations of antibodies that bind, block, or modulate human acetylcholine receptors in myasthenia gravis. 347 35

A case of amyotrophic lateral sclerosis was observed developing three months after thymectomy in a woman aged 52 years. The patient had been referred for thymectomy because of myasthenic signs increasing in intensity since 2 years. Myasthenia was confirmed by electrophysiological investigations, and the diagnosis was: myasthenic syndrome and suspected thymoma. During nearly 5 years of follow-up the following observations were made: there was a correlation between thymectomy and the development of ALS syndrome, thymosine administration produced clinical improvement, thymosine administration improved the function of thymus-dependent lymphocytes, thymosine withdrawal (due to non-availability) produced exacerbation of symptoms.
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PMID:[Syndrome of amyotrophic lateral sclerosis after thymectomy performed for myasthenic syndrome]. 402 38

Increasing numbers of patients are being recognized with neurological abnormalities associated with the immunochemical changes of plasma cell disease. To illustrate the wide spectrum of clinical disorders that can be found, I discuss in detail 5 patients: 2 with neuropathy, 3 with amyotrophic lateral sclerosis (ALS), all of whom had serum monoclonal paraproteinemia. In addition, I report in tabular form 6 patients with paraproteinemia and the following clinical presentations: 1) systemic lupus with polyneuropathy and severe cerebritis, 2) myasthenia gravis with thymoma, 3) polymyositis, 4) polymyositis, arthritis and Grave's disease, 5) relapsing polyneuritis (one of the original patients diagnosed by Austin) and 6) ALS, dystonia and parkinsonism. Major improvements in clinical condition occurred sometimes, but not always, coincident with reductions in the levels of the paraprotein using prednisone, cyclophosphamide, chlorambucil and plasma exchange treatments even in some of the patients who had the clinical appearance of ALS. Patients with neuromuscular diseases should be routinely screened with serum immunoelectrophoresis for monoclonal gammopathy. If a monoclonal gammopathy is found and if the disease is serious, then those patients should be treated as if they had an autoimmune disorder.
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PMID:Neuropathy and motor neuron syndromes associated with plasma cell disease. 647 86

Ptosis is not a feature observed in amyotrophic lateral sclerosis (ALS). We describe two old women with bulbar-onset ALS and rapid progression, in whom ptosis and diplopia were noted. They did not improve on pyridostigmine or steroids. Antibodies against acetylcholine receptor were negative, thymoma was excluded, but neurophysiological showed marked neuromuscular transmission failure in orbicularis oculi. We discuss the association between ALS and ocular myasthenia gravis in these cases.
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PMID:Amyotrophic lateral sclerosis patients and ocular ptosis. 1792 Jan 89

An adult male with thymomatous myasthenia gravis (MG) and a motor neuron syndrome simulating amyotrophic lateral sclerosis is reported. After thymectomy and corticosteroid therapy, the MG remitted. During 4 years of follow-up, the lower motor neuronsigns in the upper limbs and upper motor neuron signs in the lower limbs remained unchanged. Literature concerning paraneoplastic neurological syndromes associated with thymoma has been reviewed.
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PMID:Myasthenia gravis, motor neuron syndrome and thymoma. 2950 83