103,375 research outputs found
Miastenia gravis: perfil clínico de uma série de 20 casos.
No full textTrabalho de Conclusão de Curso - Universidade Federal de Santa Catarina. Curso de Medicina. Dapartamento de Clínica Cirúrgica
Fatigue and Muscle Atrophy in a Mouse Model of Myasthenia Gravis Is Paralleled by Loss of Sarcolemmal nNOS
No full textMyasthenia Gravis (MG) patients suffer from chronic fatigue of skeletal muscles, even after initiation of proper immunosuppressive medication. Since the localization of neuronal nitric oxide synthase (nNOS) at the muscle membrane is important for sustained muscle contraction, we here study the localization of nNOS in muscles from mice with acetylcholine receptor antibody seropositive (AChR+) experimental autoimmune MG (EAMG). EAMG was induced in 8 week-old male mice by immunization with AChRs purified from torpedo californica. Sham-injected wild type mice and mdx mice, a model for Duchenne muscular dystrophy, were used for comparison. At EAMG disease grade 3 (severe myasthenic weakness), the triceps, sternomastoid and masseter muscles were collected for analysis. Unlike in mdx muscles, total nNOS expression as well as the presence of its binding partner syntrophin ?-1, were not altered in EAMG. Immunohistological and biochemical analysis showed that nNOS was lost from the muscle membrane and accumulated in the cytosol, which is likely the consequence of blocked neuromuscular transmission. Atrophy of all examined EAMG muscles were supported by up-regulated transcript levels of the atrogenes atrogin-1 and MuRF1, as well as MuRF1 protein, in combination with reduced muscle fiber diameters. We propose that loss of sarcolemmal nNOS provides an additional mechanism for the chronic muscle fatigue and secondary muscle atrophy in EAMG and MG
Comparison of diagnostic tests in myasthenia gravis
No full textResults of 3 tests, intravenous edrophonium chloride, EMG, and acetylcholine receptor antibody testing, were compared in patients with generalised and ocular myasthenia gravis. None of the 3 tests was positive in any patient with a diagnosis other than myasthenia. However, equivocal results were obtained with edrophonium and EMG testing in some patients with myasthenia gravis and in patients with other diseases. It is concluded from this survey that antibody and edrophonium testing were equally efficient in detecting generalised myasthenia gravis. Edrophonium testing was superior in ocular myasthenia gravis. Although the yields from each test varied, all 3 tests were needed for the evaluation of some myasthenia gravis patients as each test may provide additional information
Antibodies to acetylcholine receptor in parous women with myasthenia: evidence for immunization by fetal antigen
No full textThe weakness in myasthenia gravis (MG) is mediated by autoantibodies against adult muscle acetylcholine receptors (AChR) at the neuromuscular junction; most of these antibodies also bind to fetal AChR, which is present in the thymus. In rare cases, babies of mothers with MG, or even of asymptomatic mothers, develop a severe developmental condition, arthrogryposis multiplex congenita, caused by antibodies that inhibit the ion channel function of the fetal AChR while not affecting the adult AChR. Here we show that these fetal AChR inhibitory antibodies are significantly more common in females sampled after pregnancy than in those who present before pregnancy, suggesting that they may be induced by the fetus. Moreover, we were able to clone high-affinity combinatorial Fab antibodies from thymic cells of two mothers with MG who had babies with arthrogryposis multiplex congenita. These Fabs were highly specific for fetal AChR and did not bind the main immunogenic region that is common to fetal and adult AChR. The Fabs show strong biases to VH3 heavy chains and to a single Vk1 light chain in one mother. Nevertheless, they each show extensive intraclonal diversification from a highly mutated consensus sequence, consistent with antigen-driven selection in successive steps. Collectively, our results suggest that, in some cases of MG, initial immunization against fetal AChR is followed by diversification and expansion of B cells in the thymus; maternal autoimmunity will result if the immune response spreads to the main immunogenic region and other epitopes common to fetal and adult AChR
Acetylcholine receptor antibody in the diagnosis of myasthenia gravis
No full textThe acetylcholine receptor (AchR) antibody assay has a key role in the diagnosis of myasthenia gravis. In this article, the role of AchR antibody assay in the diagnosis of ocular and generalized myasthenia gravis is reviewed, and compared to standard means of diagnosing the disease by clinical and electrophysiological methods
Clinical and functional studies of autoimmune disorders of neuromuscular transmission
No full textInherited and acquired disorders of the neuromuscular junction are an important cause of muscle weakness and fatigability. In this thesis I focus on the autoimmune disorders of neuromuscular transmission. Myasthenia Gravis (MG) is the most common of these diseases and is typically caused by antibodies against the post-synaptic acetylcholine receptor. Lambert Eaton Myasthenic Syndrome (LEMS) is a pre-synaptic disorder typically caused by antibodies against voltage gated calcium channels (VGCC). With regard to LEMS, my main aim was to gain a more complete understanding of the pathomechanisms of the disease. To date, the direct effect of LEMS IgG on presynaptic neurotransmitter release had not been investigated in detail. I examined how LEMS IgG affects neurotransmitter release by imaging action potential dependent vesicle exocytosis using a fluorescent dye. I found that LEMS IgG significantly inhibited the rate of synaptic vesicle release but this effect was lost in synapses from a Cacna1a knockout mouse. These data provide direct evidence that LEMS is caused by impaired neurotransmitter release due to an effect on P/Q-type VGCCs. With regard to MG, I studied the long-term outcome of patients with thymomatous and non-thymomatous MG after thymectomy and found that in general the outcome was favourable in the majority of patients with 34% of patients achieving complete stable remission. I also reviewed the long-term outcome of patients after a severe exacerbation of MG requiring ITU admission. Despite the significant mortality associated with severe exacerbations of MG, it was found that specialised neuro-intensive care was associated with a good long-term prognosis in the majority of patients. There were no significant differences in outcome in those with early or late onset MG. Overall the data presented in this thesis provide new insights into the pathomechanisms of LEMS IgG and provide new information regarding the long-term outcome of patients with MG
Myasthenia gravis with a monoclonal gammopathy--report of a case
No full textAn elderly man with relapsing myasthenia gravis was found to have hypergammaglobulinaemia, a monoclonal peak of gamma mobility and paraproteinaemia IgG, type K. Bence-Jones proteinuria, type K was present. This is the fourth report of myasthenia gravis associated with a monoclonal gammopathy. Myasthenia gravis is considered to be an autoimmune disease. Recent findings implicate a dysfunction of cellular immunity in the pathogenesis of both immunoproliferative and autoimmune disease. We suggest that the association of myasthenia gravis and monoclonal gammopathy in our patient might have stemmed from a disorder of T lymphocyte function
Inheritance of congenital myasthenia gravis in smooth fox terrier dogs
No full textThe phenotypes with respect to congenital myasthenia gravis of 132 Smooth Fox Terrier dogs from 25 matings were analysed. These included both prospective and retrospective matings. It was determined that congenital myasthenia gravis in this breed is inherited in an autosomal recessive manner with complete penetrance. The symbol mg is proposed for the gene for congenital myasthenia gravis in the smooth fox terrier. Attempts to maintain live affected dogs to adulthood were unsuccessful and it is concluded that this is a lethal trait..RE: 35 ref.; SC: ZA; CA; VE; BE; 0V; 7V; 0I; 0ASource type: Electronic(1) http://upei-resolver.asin-risa.ca?sid=SP:CABI&id=pmid:&id=&issn=0022-1503&isbn=&volume=75&issue=3&spage=163&pages=163-166&date=1984&title=Journal%20of%20Heredity&atitle=Inheritance%20of%20congenital%20myasthenia%20gravis%20in%20smooth%20fox%20terrier%20dogs.&aulast=Miller&pid=%3Cauthor%3EMiller%2c%20L%20M%3bHegreberg%2c%20G%20A%3bPrieur%2c%20D%20J%3bHamilton%2c%20M%20J%3C%2Fauthor%3E%3CAN%3E19842246429%3C%2FAN%3E%3CDT%3EJournal%20article%3C%2FDT%3
Perioperative evaluation of myastenia gravis
No full textA. Cardone, E. Congedo, P, Aceto, R. Sicuranza, E. Chinè, F. Caliandro, G. De Cosmo
Ann.Ital.Chir 2007; Vol. 78 / 5 – pag. 359-366
Myasthenia gravis (MG) is the prototype of antibody mediated autoimmune disease and results from the production of autoantibodies against the acetylcholine receptor (AChR) of the neuromuscular synapse. Adequate preoperative evaluation of the myasthenic patient must be carried out carefully. Age, sex, onset and duration of the disease as well as the presence of thymoma may determine the response to thymectomy. Specific attention should be paid to voluntary and respiratory muscle strength. The preoperative preparation of MG patients is essential for the success of surgery. It depends on the severity of clinical status and changes if myasthenic patients receive anticholinesterase therapy. Myasthenic patients may have little respiratory reserve, and hence depressant drugs for preoperative premedication should be used with caution and avoided in patients with bulbar symptoms. The anaesthetic management of myasthenic patient must be individualized in according to the severity of the disease and the type of surgery required. The use of regional or local anaesthesia seems warranted whenever possible. General anaesthesia can be performed safely when patient is optimally prepared and neuromuscular transmission is adequately monitored during and after surgery. Adequate postoperative pain control, pulmonary toilet, and avoidance of drugs that interfere with neuromuscular transmission will facilitate tracheal extubation. Myasthenia gravis is a disease with many implications for the safe administration of anaesthesia. The potential for respiratory compromise in these patients requires the anaesthesiologist to be familiar with the underlying disease state, as well as the interaction of anaesthetic and non-anaesthetic drugs with MG
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