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PubMed1987

[Acute effect of prostigmin on lung function and breathing of patients with myasthenia gravis at rest and following ergometric exercise].

The acute effects of a single intravenous Prostigmin injection (0.5 mg) on lung function and gas exchange during rest and bicycle ergometry were measured in 26 patients with myasthenia gravis. The mean age of the patients was 44.6 +/- 17.6 years and the mean duration of myasthenia gravis 5.4 +/- 6.3 years. Lung function parameters obtained from 15 patients showed a normal total lung capacity with an increase in functional residual capacity and residual volume, while vital capacity was diminished. While the application of Prostigmin showed no acute effects on these lung volumes, there was a significant increase in airway resistance, even into the pathologic range. Data obtained during spiro-ergometry concerning gas exchange, circulation and muscle metabolism correspond to those expected from healthy individuals; application of Prostigmin did only influence the heart rate, which can be explained by parasympathomimetic activity. We conclude that dyspnoea in patients with myasthenia gravis need not necessarily be a symptom of the illness itself but can also be caused by therapy; in the latter case bronchodilatators are required.

Adult↗

PubMed1980

Effect of adult thymectomy on the development of 1-chloro-2,4-dinitrobenzene contact sensitivity and other T lymphocyte functions in patients with myasthenia gravis.

1-Chloro-2,4-dinitrobenzene (DNCB) contact sensitivity and other T lymphocyte functions were studied in thymectomized and non-thymectomized patients with myasthenia gravis. The ability to develop contact sensitivity was reduced in patients with myasthenia gravis and was further reduced after thymectomy. Memory lymphocyte function, as measured by skin tests with common microbial antigens, was intact. A positive phytohemagglutinin (PHA) skin test was found mainly in those patients who also developed contact sensitivity to DNCB. The number of rosette-forming T cells in the peripheral blood as well as mitogen stimulation with PHA was found to be normal in thymectomized as well as non-thymectomized patients. In the thymectomized group, mitogen stimulation with concanavalin A and staphylococcal protein A was also within the normal range, while increased stimulation was obtained with pokeweed mitogen (PWM) and purified protein derivative (PPD). No alteration in mixed lymphocyte culture reactivity or immunoglobulin levels was obtained compared with healthy blood donors. On the basis of these results, it is concluded that non-thymectomized as well as thymectomized patients with myasthenia gravis may have a defective subpopulation of T cells possibly residing in the TH1-positive population. Furthermore, the increased lymphocyte stimulation obtained with PPD and PWM may indicate a reduction of suppressor cell activity after thymectomy.

Adolescent↗

PubMed1979

Symptom changes during the psychotherapy of patients with myasthenia gravis.

Four patients with myasthenia gravis were treated psychotherapeutically: two who suffered from generalized myasthenia gravis were treated without additional medical treatment. During the course of the therapy a clear correspondence of the patients' behavior and the severity of symptoms could be observed. The symptoms would improve, or even disappear, depending on the developed 'ego-strength' and the possibility of being aggressive and creative during therapy and also depending on the degree to which the 'meaning' of the symptoms could be understood. There seems to be a possibility of influencing decisively the course of myasthenia gravis by psychotherapy.

Adult↗

PubMed1989

Molecular mimicry and myasthenia gravis. An autoantigenic site of the acetylcholine receptor alpha-subunit that has biologic activity and reacts immunochemically with herpes simplex virus.

The large majority of patients with the autoimmune disease myasthenia gravis characteristically have detectable antibodies against the acetylcholine receptor (AChR). We used synthetic peptides to identify antibodies in sera of myasthenia gravis patients reactive with the human acetylcholine receptor (HuAChR) alpha-subunit, residues 160-167. Affinity purification of these antibodies, using the HuAChR alpha-subunit 157-170 peptide immobilized on thiopropyl-Sepharose, yielded IgG antibodies that bound to the native AChR and inhibited the binding of alpha-bungarotoxin to the receptor. The HuAChR alpha-subunit 160-167 peptide demonstrated specific immunological cross-reactivity with a shared homologous domain on herpes simplex virus glycoprotein D, residues 286-293, by both binding and inhibition studies. Thus, HuAChR alpha-subunit, residues 160-167, elicits antibodies in myasthenic patients that binds to the native AChR protein and is capable of eliciting a biologic effect. Immunologic cross-reactivity of this "self" epitope with herpes simplex virus suggest that this virus may be associated with the initiation of some cases of myasthenia.

Amino Acids↗

PubMed1997

Prevention of experimental myasthenia gravis by nasal administration of synthetic acetylcholine receptor T epitope sequences.

T cell tolerization prevents and improves T cell-mediated experimental autoimmune diseases. We investigated here whether similar approaches could be used for antibody (Ab)-mediated autoimmune diseases. Myasthenia gravis, caused by IgG Ab against muscle acetylcholine receptor (AChR), is perhaps the best characterized of them. We used an animal model, experimental myasthenia gravis induced in C57Bl/6 mice by immunization with Torpedo acetylcholine receptor (TAChR), to demonstrate that nasal administration of synthetic sequences of the TAChR alpha-subunit- forming epitopes recognized by anti-TAChR CD4+ T helper cells (residues alpha150-169, alpha181-200, and alpha360-378), given before and during immunization with TAChR, causes decreased CD4+ responsiveness to those epitopes and to TAChR, reduced synthesis of anti-TAChR Ab, and prevented experimental myasthenia gravis. These effects were not induced by nasal administration of synthetic epitopes of diphtheria toxin. Secretion of IL-2, IL-4, and IL-10 by spleen T cells from TAChR immunized mice, in response to challenge with TAChR in vitro, indicated that in sham-tolerized mice only Th1 cells responded to TAChR, while peptide-treated mice had also an AChR-specific Th2 response. The TAChR peptide treatment induced also in vitro anergy to the TAChR of the spleen T cells, which was reversed by IL-2.

Administration, Intranasal↗

PubMedDate not supplied

Voice spectrography in the evaluation of myasthenia gravis of the larynx.

Myasthenia gravis is a neuromuscular disorder that affects striated muscles especially those innervated by the cranial nerves. The standard diagnostic regimen is to find a reversal of symptoms by acetylcholine esterase administration. The permanent and objective recording of this effect is the key to an accurate assessment of this test. The voice spectrograph is a noninvasive means of evaluating the voice. It has been used successfully to make a clear and specific diagnosis of myasthenia gravis as it affects the larynx. The test can be used to distinguish myasthenia gravis from other functional, anatomical and neuromuscular laryngeal disorders.

Adult↗

PubMed2003

Thymectomy for myasthenia gravis: 12-year experience.

Thymectomy has been shown to be effective in the treatment of myasthenia gravis. The logical goal of operation is the complete removal of the thymus, but there is no consensus on the selection criteria of patients for surgery and the choice of surgical approach. We retrospectively reviewed 56 patients with myasthenia gravis who had been treated surgically by transsternal radical thymectomy between January 1990 and March 2002. The patients were symptomatically grouped according to the modified Osserman clinical classification. There was 1 hospital death, and 53 patients had been followed up for between 1 month and 12 years. Improvement after thymectomy was observed in 1 of 4 patients (25%) in Osserman group I, 25 of 34 patients (74%) in Osserman group IIA, and 16 of 18 patients (89%) in combined Osserman groups IIB and IIC. Transsternal radical thymectomy is an effective therapy for myasthenia gravis. Sustained improvement is achievable in female patients with moderate to severe symptoms and in patients with thymic hyperplasia.

Adolescent↗

PubMed2002

The ProSeal laryngeal mask in myasthenia gravis.

This case describes the anaesthesia management of a patient with myasthenia gravis who required mastectomy with axillary lymph node clearance. After withholding medical therapy for the myasthenia preoperatively on the day of surgery, anaesthesia was maintained with halothane, nitrous oxide and a remifentanil infusion. Muscle relaxants were avoided, facilitated by the use of a ProSeal (Intravent, Orthofix, Maidenhead, United Kingdom) laryngeal mask airway for positive pressure ventilation. The ProSeal laryngeal mask airway is a new laryngeal mask device with a modified cuff and a drainage tube which has been shown to have advantages over older designs for use during positive pressure ventilation. The rationale for the management of this patient with myasthenia is discussed.

Aged↗

PubMed2004

Is the degree of sensitivity to nondepolarizing muscle relaxants related to requirements for postoperative ventilation in patients with myasthenia gravis?

The purpose of this study was to examine whether the degree of sensitivity to nondepolarizing muscle relaxants is related to the requirement for postoperative ventilatory support in patients with myasthenia gravis. Thirty-six patients with myasthenia gravis undergoing trans-sternal thymectomy were monitored by electromyography in order to assess the neuromuscular response to vecuronium. After calibration to 100% of baseline electromyographic response values using an EMG monitor, incremental doses of 5, 10 and 20 microg/kg of vecuronium were administrated to produce 95% neuromuscular blockade and to obtain a cumulative dose-response curve for each patient. A univariable logistic regression with odds ratio was used to examine the predictive variables of prolonged postoperative ventilation. Depending on their postoperative ventilatory needs, patients were divided into an early extubation group and a prolonged ventilatory group. There were no significant differences between the two groups in terms of vecuronium ED95 (prolonged ventilation group: 23.2 +/- 18 microg/kg; early extubation group: 23.2 +/- 18 microg/kg P=0.129) and vecuronium requirement to maintain less than 25% neuromuscular blockade (prolonged ventilation group: 24 +/- 1.7 mg/kg; early extubation group: 3.8 +/- 4.5 mg/kg P=0.249). There were, however, significant differences in the incidence of a history of previous respiratory crises and the presence of bulbar palsy between the early extubation and prolonged ventilation groups. History of previous respiratory crisis (odds ratio (OR), 3.5; 95% confidence interval (CI), 1.0-13; P=0.03) and presence of bulbar palsy (OR, 3.7; 95%CI, 0.9-15; P=0.049) were associated with the need for prolonged postoperative ventilation. However, we failed to demonstrate that the degree of sensitivity to nondepolarizing muscle relaxants was related to an increased requirement for postoperative ventilation in patients with myasthenia gravis.

Dose-Response Relationship, Drug↗

PubMedDate not supplied

Association of myasthenia gravis and antisynthetase syndrome: a case report.

Myasthenia gravis is a chronic disease of neuromuscular transmission caused by loss of acetylcholine receptors. It can be found in association with other autoimmune disorders. We report the case of a 47-yr-old woman affected by Myasthenia gravis who complained of fever, progressive weakness of proximal limb muscle, arthritis and Raynauds phenomenon and dyspnea. Chest X-rays and CT scan showed an interstitial lung disease; laboratory data indicated an inflammatory picture and increased serum muscle enzymes. Evaluation for infectious, metabolic, iatrogenic and neoplastic aetiologies was unrevealing. The patients clinical condition together with positive results on antisynthetase antibody assay lead to the diagnosis of antisynthetase syndrome. To our knowledge, this is the first report on the association of Myasthenia gravis with antisynthetase syndrome.

Anti-Inflammatory Agents↗

PubMed2005

Postinfectious myasthenia gravis: report of two children.

We report two children with transient myasthenia gravis preceded by viral illnesses. The first is a 5-year-old boy who developed oculobulbar weakness 2 weeks following a varicella-zoster infection. The second is a 4-year-old boy who developed facial diplegia and dysarthria several weeks following a viral pharyngitis. Myasthenia gravis was diagnosed based on the substantial decremental changes on 3 Hz repetitive motor nerve stimulation studies for the first child and on the positive edrophonium test and complete improvement in symptoms during pyridostigmine therapy for both children. In both cases, the symptoms gradually resolved and have not recurred following discontinuation of pyridostigmine. Molecular mimicry between the acetylcholine receptor and viral proteins might provide the nidus for the immune response in this variant of myasthenia gravis.

Chickenpox↗

PubMed2003

The role of thymomas in the development of myasthenia gravis.

Thymic pathology occurs in 80-90% of myasthenia gravis patients. Significant associations between different thymic alterations and clinical findings are discussed. To highlight peculiarities in thymoma-associated myasthenia gravis, we briefly review myasthenia gravis associated with thymic lymphofollicular hyperplasia (TFH) and thymic atrophy.

Animals↗

PubMed2003

Three forms of immune myasthenia.

We propose a new classification for immune myasthenia based on antibody pattern. The types of immune myasthenia presently characterized by known antibody targets segregate into three groups: type 1, in which the muscle target is the acetylcholine receptor only; type 2, in which titin antibodies are present in addition to acetylcholine receptor antibodies; and type 3, in which muscle-specific kinase antibodies are present in the absence of acetylcholine receptor antibodies. The immune target is unknown in the patients with immune myasthenia not associated with these antibodies. This classification has advantages over the present classifications as regards homogeneity of groups, etiology, mechanism of disease, and prognosis.

Antibodies↗

PubMed1976

Immunologic studies of a case of myasthenia gravis associated with pemphigus vulgaris after thymomectomy.

A case of myasthenia gravis was associated with thymoma and pemphigus vulgaris. The bullous lesions developed after partial thymomectomy, cobalt (60Co) irradiation, and 3 days' extensive sunbathing, although a retrospective study of the patient's sera by quantitative indirect immunofluorescence method indicated that antiepithelial antibody already was positive before the clinical appearance of pemphigus vulgaris. Serial observation of the patient's clinical course and titrations of antiepithelial, antimuscle, and antithymus antibodies suggested a reverse relationship between the severity of myasthenia gravis and titers of antimuscle and anitithymus antibodies, and a parallel relationship between pemphigus vulgaris and antiepithelial antibody. Review of the literature suggests a close relationship between pemphigus vulgaris and myasthenia gravis and thymoma, particularly thymoma injured by medical procedures.

Adult↗

PubMed1976

Multiple sclerosis and myasthenia gravis. A case report with single fiber electromyography.

A 34-year-old woman with long-standing multiple sclerosis had a 2-year history and physical signs of myasthenia gravis. The edrophonium chloride (Tensilon) test was positive. Repetitive stimulation of the ulnar nerve at 3 Hz did not show evidence of myasthenic response; however, a single-fiber electromyography demonstrated evidence of neuromuscular block as seen in myasthenia gravis, which was reversed to normal after intravenously administered edrophonium. The patient improved on anticholinesterase medication. It is suggested that patients with multiple sclerosis who have unusual features such as in the patient reported here should be investigated for the presence of myasthenia gravis to ensure proper treatment.

Adult↗

PubMed1977

Ultrastructural localization of the acetylcholine receptor in myasthenia gravis and in its experimental autoimmune model.

Peroxidase-conjugated alpha-bungarotoxin (P-BGT) was used for the ultrastructural localization of the acetylcholine receptor in end-plates in external intercostal muscles of four patients with myasthenia gravis, in forelimb digit extensor muscles of rats with advanced chronic experimental autoimmune myasthenia gravis, and in suitable human and rat controls. In control end-plates, the previously reported localization of acetylcholine receptor on the terminal expansions of the postsynaptic folds and, in traces, on the presynaptic membrane was confirmed. By contrast, in myasthenia gravis some postsynaptic regions bound no P-BGT; in other regions, the folds displayed only faint traces of the reaction product, or only some segments of the postsynaptic membrane showed the reaction product; finally, in some regions there was no apparent decrease in reaction product. In general, those postsynaptic regions showing the greatest decrease in P-BGT binding were also the simplest or showed the most degenerative changes, and the presynaptic staining was decreased in proportion to the decrease in the adjacent postsynaptic P-BGT binding. In the experimental animals, the abnormalities in the amount and distribution of the acetylcholine receptor were essentially like those in the more severely affected patients. Morphometric estimates of the postsynaptic acetylcholine receptor surface correlated well with the patients' clinical status and linearly with the miniature end-plate potential amplitude.

Action Potentials↗

PubMed1979

Myasthenia gravis and monoclonal IgG gammopathy.

Monoclonal IgG gammopathy of the lambda light-chain type was detected in a 51-year-old woman who had unexplained fever, muscle fatigue, and myalgia. One year later, myasthenia gravis was diagnosed. There was no evidence of myelomatosis or other malignancy. On the assumption that her M-component (gammopathic paraprotein) was related to myasthenia, she was treated with melphalan and cyclophosphamide, but her clinical condition was not improved. Despite therapeutic trials of other agents and a time course of 6 years, the quantity of the M-component remained unchanged. Serum AChR antibody activity was not located in the paraprotein peak. The findings do not support a relationship between the M-component and myasthenia gravis.

Acetylcholine↗

PubMed1979

Antibody to acetylcholine receptor in canine and human myasthenia gravis: differential cross-reactivity with human and rabbit receptor.

Anti-acetylcholine receptor (AChR) antibody (ab) was found in the serum of a dog with acute myasthenia gravis (MG) by the use of Cowan 1 strain Staphylococcus aureus to bind radiolabeled anti-AChR ab-AChR immune complexes. Fifteen months later, when the dog was in remission, there was only a very low level of the anti-AChR ab. These observations strengthen the contention that anti-AChR ab is important in the pathophysiology of myasthenia gravis. Higher titers of the canine ab were measured with rabbit than with human AChR, whereas 17 human MG sera, selected to represent a wide range of anti-AChR ab titers, were all more reactive with human AChR. The degree of cross-reactivity of human anti-AChR ab with rabbit AChR varied widely, indicating a heterogeneous population of anti-AChR ab molecules in human myasthenia gravis sera.

Animals↗