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At least 451 records · Page 25Linked to original sources

PubMed1978

Prolonged neonatal myasthenia gravis: electrophysiological studies.

A female infant with neonatal myasthenia gravis remained weak for an excessively long period compared to the usual situation in this disease process. At 71 days of age, electrophysiological studies revealed evidence of a defect in neuromuscular transmission that improved with intravenous Tensilon therapy. Repeat study at 183 days of age was normal. This case represents an unusually long time for an affected infant to have neonatal myasthenia gravis. Electrophysiological studies are of value in the diagnosis and management of patients with neonatal myasthenia gravis.

Edrophonium↗

PubMed1981

Myasthenia induced by monoclonal anti-acetylcholine receptor antibodies: clinical and electrophysiological aspects.

To investigate individual components of the humoral immune response directed against the acetylcholine receptor in experimental myasthenia, we injected monoclonal antireceptor antibody into normal rats. These antibodies were produced by cloned hybridoma lines formed by fusion of immune spleen cells with the myeloma cell line P3-X63-Ag8. Antibodies from two of seven clones induced acute experimental myasthenia, manifested by clinical weakness, decremental electromyographic response to repetitive nerve stimulation, and diminished mean amplitudes of miniature end-plate potentials (mepps): 0.55 +/- 0.02 mv (SEM) versus 0.71 mv for controls (p less than 0.001). In clinically affected animals, mepp amplitudes from the diaphragm correlated with decremental responses in the gastronemius muscle (r = -0.91, p less than 0.01). The results suggest that binding of a single antibody species to a single determinant on the acetylcholine receptor molecule is sufficient to induce acute experimental myasthenia gravis.

Animals↗

PubMed1982

Monoclonal antibody analysis of blood T-cell subsets in myasthenia gravis.

Analysis of peripheral blood T -cell subsets and B-cells in patients with myasthenia gravis was performed using monoclonal antibodies and antibody against surface immunoglobulins (SIg) in an immunofluorescent technique. We found a modest but significant decrease in percentages of OKT3- and OKT8-positive cells (thought to represent total T-cells and T-suppressor/cytotoxic cells, respectively) in myasthenics as a group. The percentage of OKT3-positive cells was significantly decrease in patients with late-onset disease (greater than 35 years old), while the percentage of OKT8-positive cells was significantly reduced in those with early-onset myasthenia (greater than 35 years old). Both thymectomized and nonthymectomized patients exhibited a decreased percentage of OKT3-positive cells. No significant difference was found between the percentages of SIg-positive cells in myasthenics and controls. Our results suggest that only modest imbalances of circulating immunoregulatory lymphocytes occur in myasthenia gravis; however, it is conceivable that the small differences observed in this study may reflect pathogenetically important reductions in a functionally distinct lymphocyte subpopulation.

Adolescent↗

PubMed1983

Myasthenia gravis in children: long-term follow-up.

We report observations made on 149 patients with juvenile myasthenia gravis studied from onset of disease for as long as 40 years. Median follow-up was 17 years; minimum was 4 years. Eight other patients with congenital myasthenia gravis were studied separately. Of the juvenile myasthenic patients, 85 (57%) underwent thymectomy because of diseases severity. In juvenile myasthenia gravis, a spontaneous remission rate of 22.4 per 1,000 person-years was observed, regardless of disease duration. A remission rate of 260 per 1,000 person-years was seen during the first year after thymectomy, with a rate of 95 per 1,000 person-years during the next 2 years. Early surgery, presence of bulbar symptoms, absence of ocular signs or generalized symptoms, onset of symptoms between ages 12 and 16, and presence of other immune disease were associated with increased postoperative remission rates. Epilepsy (4 patients) and neoplasia (7 patients) were the most frequent associated nonimmune disorders; rheumatoid arthritis (5 patients), juvenile-onset diabetes mellitus (3 patients), asthma (3 patients), and thyroid disease (3 patients) were the most frequent associated immune diseases.

Adolescent↗

PubMed1983

Prognosis of ocular myasthenia.

A retrospective study of 108 patients with myasthenia gravis who had solely ocular symptoms and signs at onset was carried out to identify factors influencing prognosis. Increasing duration of pure ocular myasthenia was associated with a decreasing risk of late generalized symptoms; only 9 (15%) of the observed generalizations occurred after more than 2 years of solely ocular symptoms. Increasing age at onset was associated with greater risk of respiratory crisis or death caused by myasthenia, whereas patients younger at onset had a greater chance of a benign outcome. Neither systemic curare tests nor responses to repetitive nerve stimulation had prognostic value.

Adolescent↗

PubMed1986

Effect of thymectomy on blood T-cell subsets in myasthenia gravis.

We studied peripheral blood mononuclear T-cell subsets in 23 patients with myasthenia gravis who had undergone thymectomy at least one year before study. An increase in the T4+/T8+ (helper-inducer/suppressor-cytotoxic cell) ratio was seen, similar to that previously reported in nonthymectomized patients with myasthenia gravis. Six patients were studied before and after thymectomy and no consistent alteration in the pattern of T-cell subsets was detected. We were not able to demonstrate a quantitative effect of thymectomy on peripheral blood mononuclear T-cell subsets in patients with myasthenia gravis.

Adult↗

PubMed1986

The pathophysiology of penicillamine-induced myasthenia gravis.

The temporal course and pathophysiology of penicillamine-induced myasthenia gravis were studied in detail in a typical case. Our results suggest that this disorder and idiopathic autoimmune myasthenia gravis share the same essential pathophysiological features, including the presence of anti-acetylcholine receptor (AChR) antibody, serum-induced blockade of AChRs, antibody-mediated accelerated degradation of AChRs, and a resultant quantitative reduction in available junctional AChRs. An initial severe reduction in junctional AChRs was reversed and the patient recovered, both within 8 months of stopping penicillamine. Our data suggest that penicillamine probably produced myasthenia gravis by initiating a new autoimmune response rather than by enhancing ongoing autoimmunity.

Animals↗

PubMed1997

Altered intrathymic T-cell repertoire in human myasthenia gravis.

In myasthenia gravis, the thymus is thought to be the primary site of autosensitization. We investigated the V beta T-cell repertoire at different intrathymic differentiation stages in 17 patients with myasthenia gravis and 8 age-matched control subjects by tricolor immunofluorescence, using a panel of six anti-V beta antibodies. We observed an increased expression of V beta 5.1 and V beta 8 subfamilies in the patients compared to the control subjects. These increases were observed not only in mature cells but also in the latest thymic precursors of mature cells (double-positive CD3 high), while there was no change in intermediate precursors (double-positive CD3 low), pointing to biased selection during intrathymic differentiation. In addition, there was a strong correlation between the percentage of V beta 5.1+ and V beta 8+ cells among both the CD4 and CD8 subsets in the patients, but not in control subjects, suggesting that thymic events relevant to the disease lead to these selected populations. Finally, location studies of V beta 5.1+ cells on thymic sections indicated that these cells were overrepresented both in the core of germinal centers and in perifollicular areas of hyperplastic thymuses, suggesting a role in the autoimmune response. Taken together, these findings are compatible with the hypothesis of a biased intrathymic selection in myasthenia gravis.

Adolescent↗

PubMed1980

Inhibition of alpha-bungarotoxin binding to acetylcholine receptors by antisera from animals with experimental autoimmune myasthenia gravis.

Conditions are described for an assay that allows the percent inhibition of alpha-bungarotoxin binding to acetylcholine receptors by antisera and monovalent antigen-binding fragments of antibody molecules (Fab) to be determined. Anti-Torpedo californica acetylcholine-receptor antisera, prepared in New Zealand White rabbits and Lewis rats, were tested for the ability to inhibit [125I]-alpha-bungarotoxin binding to membrane-associated and detergent-solubilized T californica acetylcholine receptors. Similar inhibition studies were performed using rabbit antisera and antigen-binding fragments prepared against each of the four acetylcholine receptor subunits. Antisera and antigen-binding fragments prepared against intact receptor could inhibit a maximum of 50% of the alpha-bungarotoxin binding to solubilized receptor. The results using monovalent antigen-binding fragments indicated that the inhibition was not due to antibody-mediated aggregation of receptor molecules. Rabbits and rats immunized with receptor denatured by sodium dodecyl sulfate all produced antisera that could bind to nondenatured receptor, but none of these animals developed experimental autoimmune myasthenia gravis. These results suggest that the antigenic determinants present on acetylcholine receptors responsible for induction of experimental autoimmune myasthenia gravis are lost with sodium dodecyl sulfate denaturation. A strong correlation was also observed between the presence of experimental autoimmune myasthenia gravis in rats and rabbits and the ability of the antisera from these animals to inhibit 50% of alpha-bungarotoxin binding to solubilized acetylcholine receptors.

Animals↗

PubMed2003

Maximal voluntary ventilation in myasthenia gravis.

Assessment of respiratory muscle weakness is important at all stages of myasthenia gravis. The maximal voluntary ventilation (MVV) is an objective dynamic method for measuring the working capacity of respiratory muscles. The clinical value of this method was studied in 24 newly diagnosed patients with myasthenia gravis, classified according to Osserman criteria (grades I, IIa, and IIb). The MVV values were normal in group I, whereas a characteristic "myasthenic pattern" of decremental respiratory volumes was demonstrated during MVV in group IIa and IIb patients, with or without dyspnea. Despite some limitations and lack of specificity, MVV may be a valuable tool in the assessment of respiratory dysfunction in patients with myasthenia gravis. Muscle Nerve, 27: 715-719, 2003

Adrenal Cortex Hormones↗

PubMed2005

Pulmonary function tests and blood gases in worsening myasthenia gravis.

The aim of this study was to determine whether pulmonary function tests have a role in predicting the need for ventilation support in myasthenia gravis. Medical records were reviewed for 42 patients with severe myasthenia gravis who required 55 admissions to the intensive care unit. Patients with a vital capacity of more than 20 ml/kg, a maximal expiratory pressure more than 40 cm H(2)O, or a maximal inspiratory pressure more negative than -40 cm H(2)O are unlikely to require mechanical ventilation. A decline of 30% or more in maximal inspiratory pressure predicted a group at higher risk of requiring mechanical or noninvasive ventilation. Hypercapnia was frequent and was more common in patients who required mechanical ventilation. Worsening of these pulmonary function and blood gas values in patients with myasthenia gravis may guide decisions about intubation and ventilatory support.

Blood Gas Analysis↗

PubMedDate not supplied

Myasthenia gravis: a personal view of pathogenesis and mechanism, part 1.

A review of our current knowledge of the etiology and pathogenesis of myasthenia gravis is presented, with particular emphasis on the immunological aspects of the disease. Part 1, published in this issue, deals with the clinical and genetic features of myasthenia gravis which led to the autoimmune theory of the etiology of this disease. Various theories in this field are reviewed, and recent advances in our knowledge of the acetylcholine receptor protein, and its immunology, are examined. Part 2, which will appear in the March/April issue, provides a review of the dysfunction of physiology, pharmacology, and structure of the neuromuscular junction in myasthenia gravis, and the part played by the autoimmune process.

Adult↗

PubMedDate not supplied

Myasthenia gravis: a personal view of pathogenesis and mechanism, part 2.

A review of our current knowledge of the etiology and pathogenesis of myasthenia gravis is presented, with particular emphasis on the immunological aspects of the disease. Part 1, published in the January/February issue of MUSCLE & NERVE, dealt with the clinical and genetic features of myasthenia gravis which led to the autoimmune theory of the etiology of the disease. Part 2, which appears in this issue, provides a review of the dysfunction of physiology, pharmacology, and structure of the neuromuscular junction in myasthenia gravis, and the part played by the autoimmune process.

Autoimmune Diseases↗

PubMedDate not supplied

Acetylcholine receptor antibodies in the diagnosis of human and experimental myasthenia gravis.

Aspects of acetylcholine receptor immunology and circulating receptor antibodies are reviewed with regard to both human and experimental myasthenia gravis. Receptor antibodies that have negligible cross-reactivity with skeletal muscle receptor can nonetheless cause destruction of the postsynaptic motor endplate area. Antibodies to mammalian skeletal muscle receptor can bind in-situ receptors. Transfer of myasthenic IgG increases neurophysiologic symptoms in rabbits showing slight signs of experimental myasthenia gravis, suggesting a block of in-situ receptors. Determination of receptor antibodies using RIA tests and partially purified human skeletal muscle receptor has been evaluated in the diagnosis of myasthenia gravis. Ninety percent of Swedish myasthenic patients in one study were found to have receptor antibodies. A rough correlation has been found between antibody titer and the severity of disease. Immunosuppressive treatment and thymectomy decrease the titer. In patients with thymoma, high antibody titers remain. When taken together, antibody-titer determination and electrophysiologic tests--particularly single-fiber electromyography--are very valuable diagnostic tools.

Animals↗

PubMedDate not supplied

Acquired canine myasthenia gravis: immunocytochemical localization of immune complexes at neuromuscular junctions.

In the acquired form of myasthenia gravis in dogs, there are circulating antibodies to acetylcholine receptors (AChRs) and a reduction in the number of AChRs in the postsynaptic membrane. In this study, immune complexes were localized at the neuromuscular junctions in biopsy samples from 10 myasthenic dogs by immunocytochemical means employing conjugates of staphylococcal protein A and horseradish peroxidase. Immune complexes were observed in approximately 70% of the neuromuscular junctions studied in both type 1 and type 2 myofibers. Thus, acquired canine myasthenia gravis appears to involve immune-mediated mechanisms that destroy AChRs in a manner similar to myasthenia gravis in humans. Protein A was also observed to bind principally to elastic fibers in small arteries and arterioles of some myasthenic and control dogs; however, the significance of that localization is unknown.

Animals↗

PubMed1994

Passive transfer of seronegative myasthenia gravis to mice.

Muscle weakness in myasthenia gravis is due to autoantibody-induced loss of functional acetylcholine receptors (AChR). About 15% of myasthenia gravis patients, however, do not have detectable anti-AChR antibodies. To investigate the effect of their plasma immunoglobulins on neuromuscular transmission, mice were injected with plasma (and in some cases purified immunoglobulin G (IgG)) from 7 "seronegative" myasthenia gravis (SMG) patients, and neuromuscular transmission parameters were examined. When injected for 15 days, all patients' plasma caused reductions in miniature endplate potential amplitudes, while endplate potential quantal content was significantly reduced by plasma from 4 of the 7 patients. There were no changes in ACh-induced depolarization or single channel properties, and 125I-alpha-bungarotoxin binding studies showed no effect on AChR number, except in 1 case. Purified IgG injected for 3 days had similar effects to plasma injected for 15 days. Our findings confirm that SMG is autoantibody mediated and that there are pathogenic IgG antibodies. SMG appears to be a heterogeneous disorder and the target(s) for the antibodies may be diverse.

Acetylcholine↗

PubMed1999

Identification of autoantibodies associated with rippling muscles and myasthenia gravis that recognize skeletal muscle proteins: possible relationship of antigens and stretch-activated ion channels.

The role of mechanosensitive calcium channels in skeletal muscle physiology is not understood. This study takes advantage of an autoimmune neuromuscular disorder (myasthenia gravis associated with rippling muscles) to identify components in the skeletal muscle myocyte that may play a role in mechanosensitive calcium channel activity. Rippling muscles are characterized by stretch or percussion activated wave-like muscle contractions that do not require motor unit action potentials for propagation. Autoantibodies from the sera of patients with autoimmune rippling muscles (associated with myasthenia gravis) are directed against high molecular weight muscle proteins. Some of these proteins are uniquely recognized by antisera from patients with autoimmune rippling muscles. This suggests these autoantigens are distinct from those normally associated with myasthenia gravis, and may play a role in the mechanosensitive activation of muscle contraction.

Autoantibodies↗

PubMed1993

Suppression of experimental autoimmune myasthenia gravis by epitope-specific neonatal tolerance to synthetic region alpha 146-162 of acetylcholine receptor.

A gene conversion event between Ebb and Abb in the B6.C-H-2bm12 (bm12) strain, which alters three amino acids in the C-terminal half of the first domain of Abb (Ile-67-->Phe; Arg-70-->Gln; Thr-71-->Lys) resulted in resistance to experimental autoimmune myasthenia gravis (EAMG) pathogenesis. To study the effect of bm12 mutation on the T-cell responses to epitopes of acetylcholine receptor (AChR)-alpha subunit, C57BL6 (B6) and bm12 mice were primed with Torpedo californica AChR, and the profiles of T-lymphocyte proliferation were determined with 18 synthetic overlapping peptides encompassing the entire extracellular portion of the AChR-alpha subunit. The proliferative responses of AChR-primed bm12 lymphocytes were markedly reduced to two (alpha 146-162 and alpha 182-198) of the three AChR peptides (alpha 111-126, alpha 146-162, and alpha 182-198) that are immunodominant in B6 mice. Thus, the Ab residues encompassing the region 67-71 determine the immunogenicity of two of the AChR-alpha subunit T-cell epitopes. To test the involvement of AChR-alpha chain epitopes within peptide alpha 146-162 in EAMG pathogenesis, B6 mice were neonatally tolerized with soluble peptide alpha 146-162, and subsequently immunized with AChR in complete Freund's adjuvant. Neonatal tolerance to AChR or to peptide alpha 146-162 reduced the incidence of clinical myasthenia gravis and suppressed serum anti-AChR antibodies. This indicates the involvement of T-cell epitopes within AChR-alpha subunit region alpha 146-162 in EAMG pathogenesis. Neonatal tolerance to peptide alpha 146-162 could have caused specific clonal deletion, and/or clonal anergy, and/or recruited suppressor cells to prevent clinical EAMG. Presumably, epitope(s) with AChR alpha 146-162, in the context of Ab encompassing region 67-71, stimulate specific T helper cells which interact with specific B cells to produce pathogenic antibodies, the primary culprit causing the end plate lesion in patients with myasthenia gravis.

Amino Acid Sequence↗