Immunobiology of myasthenia gravis, experimental autoimmune myasthenia gravis, and Lambert-Eaton syndrome.
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Animals↗
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Content of acetylcholine receptor and antibodies bound to receptor in myasthenia gravis, experimental autoimmune myasthenia gravis, and Eaton-Lambert syndrome.
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Adult↗
Immunological similarities between an experimental autoimmune myasthenia gravis model and human myasthenia gravis.
The induction of experimental autoimmune myasthenia gravis (EAMG) in rabbits after immunization with an acetylcholine (ACh) conjugate was found to possess immunological similarities with human myasthenia gravis. Anti-ACh antibodies, present in human sera, recognized the antigenic determinant, glutarylcholine, used to raise anti-ACh antibodies in rabbits. Identification of anti-anti-ACh antibodies in MG patients enabled us to test for recognition of the anti-ACh antibodies present in rabbit sera. The reverse, the recognition of rabbit auto-anti-anti-ACh antibodies by human anti-ACh antibodies was also tested and found to be specific.
Acetylcholine↗
The significance of titin antibodies in myasthenia gravis--correlation with thymoma and severity of myasthenia gravis.
Myasthenia gravis (MG) is caused by autoantibodies to acetylcholine receptors (AChR). Non-AChR muscle autoantibodies, such as titin antibodies, are present in sera of many MG patients. To study the correlation between titin antibodies and the features of MG, the cDNA segment encoding MGT-30 was amplified and sequenced. The cloned MGT-30 cDNA was expressed in vector pET-30a, and then transfected into E.coli. BL21. We examined titin antibodies in sera of 265 normal subjects, 154 MG patients with different thymic pathology and 48 patients with other neurological diseases. Titin antibodies occurred more frequently in MGT, especially in MG with epithelial predominant-thymoma, and were correlated with the severity of disease. The levels of titin antibodies were reduced 6 months after thymectomy. The specificity of titin antibodies for the detection of thymoma was higher than that of CT examination in MG with thymoma. These results suggest that titin antibodies could be useful in both diagnosis and follow-up of MG patients with thymoma.
Adolescent↗
Immunotherapy of ocular myasthenia gravis reduces conversion to generalized myasthenia gravis.
BACKGROUND: Several retrospective studies have suggested that immunotherapy, including prednisolone, azathioprine and thymectomy, reduces progression of ocular myasthenia gravis to generalized myasthenia gravis. This study examines the effect of immunotherapy on generalization rates in ocular myasthenia patients who are acetylcholine receptor (AChR) antibody-positive. METHODS: Retrospective record review of 34 patients from three university-based hospitals with neurology and neuro-ophthalmology services in Australia. In all patients, positive AChR antibodies were recorded, the initial symptoms were purely ocular, and all had at least 2 years of follow-up. The patients who developed generalized myasthenia gravis were compared with those who remained purely ocular. RESULTS: There were 21 patients who developed generalized myasthenia gravis. Of these 21, only 2 (9.5%) had received prior immunotherapy. Among the 13 patients whose symptoms remained purely ocular, 10 (76.9%) had received prior immunotherapy. CONCLUSIONS: In this study, most of the patients who progressed from ocular myasthenia to generalized myasthenia had not received prior immunotherapy. This study adds weight to the call for a prospective trial of early immunotherapy in patients with ocular myasthenia.
Adult↗
[Late onset forms of myasthenia gravis. Comparison with early-onset myasthenia gravis].
INTRODUCTION: The incidence of myasthenia gravis appears to be increasing in elderly but few studies have been devoted to late onset myasthenia gravis. PATIENTS AND METHODS: We retrospectively compared myasthenic patients with an age at onset above or below 35 years which were observed in two departments of Neurology from 1980 to 2002. RESULTS: 81 cases were included, 28 of which were late onset myasthenia gravis. The two populations were similar in terms of sex-ratio, clinical symptoms, course of the disease and therapeutic response. There was a trend for older patients to present more frequently at onset with dysphagia and axial or proximal involvement, and to have extra-ocular symptoms more quickly. Antibodies against acetylcholine receptor and striated muscle were statistically more frequent in elder patients. CONCLUSIONS: A late onset is not a factor of poor prognosis in myasthenia gravis and older patients must be treated in the same way than younger ones.
Adolescent↗
The motor end plate in myasthenia gravis and in experimental autoimmune myasthenia gravis. A quantitative ultrastructural study.
Neuromuscular junction ultrastructure in rat forelimb digit extensor muscle was sequentially and quantitatively investigated in experimental autoimmune myasthenia gravis (EAMG). Experimental animals received a single dose of highly purified eel-electroplax acetylcholine receptor protein plus complete Freund's adjuvant and B. pertussis organisms. During the first 7 days (latent period) after immunization the experimental end plates remained normal. Between day 7 and 11 (acute phase) mononuclear cells infiltrated those regions of muscle where the end plates were located and the was sudden degeneration of the postsynaptic regions with splitting away of the abnormal junctional folds from the underlying muscle fibers. Macrophages entered the gaps arising between the muscle fibers and the separating postsynaptic folds and removed the degenerating folds by phagocytosis. The nerve terminals were displaced from their usual location but maintained their structural integrity. After day 11 (chronic phase) the inflammatory reaction subsided and the nerve terminals returned to the highly simplified postsynaptic regions. Subsequently the postsynaptic folds were reconstituted and again they degenerated. The degeneration involved especially the tips of the folds where acetylcholine receptor sites are concentrated. Immature junctions with poorly differentiated postsynaptic regions and nerve sprouts near end plates were also observed. In two animals that relapsed on day 27 and 33, respectively, degeneration of the postsynaptic folds was more intense than in the remaining animals that had not relapsed during the chronic phase. Morphometric analysis of the end plates demonstrated significant decreases in the postsynaptic membrane length, in the postsynaptic membrane density and in the postsynaptic to presynaptic membrane length ratio in chronic EAMG. In addition, the concentration of synaptic vesicles in the nerve terminals was increased in acute and chronic EAMG while the nerve terminal area was decreased in acute EAMG. The alterations in the nerve terminal may be secondary to the postsynaptic changes. The postsynaptic region is the primary target of the autoimmune reaction in EAMG and the ultrastructural and morphometric abnormalities of the end plate in the chronic phase of the syndrome closely resemble those which have been observed in human myasthenia gravis.
Animals↗
Intravenous immunoglobulin for myasthenia gravis.
BACKGROUND: Myasthenia gravis is an autoimmune disease in which autoantibodies interfere with neuromuscular transmission. As with other autoimmune diseases, people with myasthenia gravis would be expected to benefit from intravenous immunoglobulin. OBJECTIVES: The objective of this review was to examine the efficacy of intravenous immunoglobulin for treating exacerbations of myasthenia gravis or for chronic myasthenia gravis. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group trials register (March 2005) and MEDLINE (January 1966 to March 2005) using 'myasthenia gravis' and 'intravenous immunoglobulin' as the search terms. SELECTION CRITERIA: We included all randomised or quasi-randomised trials in which intravenous immunoglobulin was compared with no treatment, placebo or plasma exchange, in people with myasthenia gravis. DATA COLLECTION AND ANALYSIS: One author extracted the data and the two others checked these data and the source from which they were derived. For methodological reasons, no formal meta-analysis was performed. MAIN RESULTS: We identified five randomised controlled trials, all of which investigated short-term benefit. The first study of 87 participants with exacerbation found no statistically significant difference between immunoglobulin and plasma exchange after two weeks. The second study of 12 participants with moderate or severe myasthenia gravis treated in a crossover design trial found no statistically significant difference in the efficacy of immunoglobulin and plasma exchange after four weeks. The third study with 15 participants with mild or moderate myasthenia gravis found no statistically significant difference in efficacy of intravenous immunoglobulin and placebo after six weeks. The fourth study terminated early. It included 33 participants with moderate exacerbations of myasthenia gravis and showed no statistically significant difference in the efficacy of intravenous immunoglobulin and methylprednisolone. The fifth trial including 173 people with myasthenia gravis exacerbations, showed no superiority of intravenous immunoglobulin 1 g/kg on two consecutive days over intravenous immunoglobulin 1 g/kg on a single day. AUTHORS' CONCLUSIONS: In severe exacerbations of myasthenia gravis, one randomised controlled trial did not show a significant difference between intravenous immunoglobulin and plasma exchange. Another showed no significant difference in efficacy between 1 g/kg and 2 g/kg of intravenous immunoglobulin. A further trial showed no significant difference between intravenous immunoglobulin and oral methylprednisolone. In chronic myasthenia gravis, there is insufficient evidence from randomised trials to determine whether intravenous immunoglobulin is efficacious. More research is needed to determine whether intravenous immunoglobulin reduces the need for steroids as suggested by two case series.
Humans↗
Intravenous immunoglobulin for myasthenia gravis.
BACKGROUND: Myasthenia gravis is an autoimmune disease. In up to 90 per cent of cases IgG autoantibodies to the nicotinic acetylcholine receptor are detectable which mediate the neuromuscular transmission disorder. As with other autoimmune diseases, patients would be expected to benefit from intravenous immunoglobulin. Case series and two randomised controlled trials suggest that intravenous immunoglobulin may be beneficial. OBJECTIVES: The objective of this review is to examine the efficacy of intravenous immunoglobulin for treating exacerbations of myasthenia gravis or for chronic myasthenia gravis. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group trials register (21 July 2002) and MEDLINE (January 1966 to July 2002) using 'myasthenia gravis' and 'intravenous immunoglobulin' as the search terms. SELECTION CRITERIA: All randomised or quasi-randomised trials in which intravenous immunoglobulin was compared with no treatment, placebo or plasma exchange, in people with myasthenia gravis who were diagnosed by an internationally accepted definition. DATA COLLECTION AND ANALYSIS: One author extracted the data and the two others checked these data and the source from which they were derived. For methodological reasons, no formal meta-analysis was performed. MAIN RESULTS: We identified four randomised controlled trials (147 participants in total), all investigating short-term benefit. In the first study of 87 people with myasthenia gravis exacerbation, comparing intravenous immunoglobulin and plasma exchange, there was no statistically significant difference between the efficacy of the two treatments after two weeks. In the second study 12 people with moderate or severe myasthenia gravis were treated in a cross-over design trial with intravenous immunoglobulin or plasma exchange: no statistically significant difference in the efficacy of the two treatments was found after four weeks. In the third study 15 people with mild or moderate myasthenia gravis received intravenous immunoglobulin or a placebo: no significant difference in efficacy of intravenous immunoglobulin or placebo was found six weeks after treatment. The last study, which included 33 people with moderate exacerbations of myasthenia gravis, compared intravenous immunoglobulin and methylprednisolone and showed no statistically significant difference in the efficacy of the two treatments. REVIEWER'S CONCLUSIONS: One randomised controlled trial did not show a significant difference between intravenous immunoglobulin and plasma exchange for treatment of severe exacerbations of myasthenia gravis. There is no evidence from randomised controlled trials to determine whether intravenous immunoglobulin for moderate or severe myasthenia gravis improves functional outcome or has a sparing effect on steroid dosage, nor is there sufficient evidence to favour intravenous immunoglobulin over steroids in moderate exacerbations. Further randomised controlled trials are needed.
Humans↗
Myasthenia gravis: familial occurrence. A study of 1100 myasthenia gravis patients.
Eleven-hundred myasthenia gravis cases observed by the author in a period of 37 years are reviewed. The ratio of familial incidence was 4.23%. Transitory (neonatal) myasthenia in new-born babies should be separated from the familial cases. In familial myasthenia gravis both maternal and paternal line can occur. The majority of the cases are similar to the generalized, acquired myasthenia gravis, still there are some myasthenic familial congenital patients, too. Some rare instances are reported, among them a unique family with six sisters suffering from myasthenia gravis. Genetic line and HLA antigens' role are dealt with. Observation of familial myasthenia cases may contribute to the knowledge of the immunologic and clinicopathologic background of the disease.
Adolescent↗
Establishment of a mouse model of myasthenia gravis which mimics human myasthenia gravis pathogenesis for immune intervention.
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Animals↗
Freeze-fracture, labelled-replica, and electrophysiological studies of junctional fold destruction in myasthenia gravis and experimental autoimmune myasthenia gravis.
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Adult↗
The role of major histocompatibility complex genes in myasthenia gravis and experimental autoimmune myasthenia gravis pathogenesis.
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Animals↗
Active management in patients with ocular manifestations of myasthenia gravis.
PURPOSE: Myasthenia gravis can cause variable strabismus with disabling diplopia and/or poor cosmesis. A retrospective study of a group of patients with myasthenia gravis or 'myasthenia gravis like' syndromes was made. METHODS: The study group consisted of patients who had undergone botulinum toxin treatment and/or surgery for disabling diplopia, poor cosmesis or both. Surgical treatment was by conventional techniques including recess/resect, posterior fixation, superior oblique tenotomy and adjustable sutures. RESULTS: There were 9 patients in the study group (8 female, 1 male). Age at surgery ranged from 21 to 59 years (mean 46 years). Six were symptom-free following treatment. Two, although symptomatically improved, had occasional diplopia. One patient failed treatment and required an occlusive contact lens. CONCLUSIONS: The ocular manifestations of myasthenia gravis or 'myasthenia gravis like' syndromes may respond to surgery and/or botulinum toxin injection. Active intervention should be considered when deviations become stable. To our knowledge this is the first report of the use of botulinum toxin in such patients.
Adolescent↗
Plasma exchange for myasthenia gravis.
BACKGROUND: Myasthenia gravis is an autoimmune disease mediated by auto-antibodies direct against the nicotinic receptor for acetylcholine. Patients would be expected to benefit from plasma exchange. Non-randomised studies suggest that plasma exchange is beneficial in the short term. OBJECTIVES: To examine the efficacy of plasma exchange in the short and long term treatment of myasthenia gravis. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group register (searched 17 July 2002) and MEDLINE (January 1966 to June 2002) for randomised controlled trials using myasthenia gravis as the search term. We checked the bibliographies in reports of randomised trials and contacted one author to identify additional published or unpublished data. SELECTION CRITERIA: Types of studies: All randomised or quasi-randomised studies. TYPES OF PARTICIPANTS: All patients with myasthenia gravis who were diagnosed by an internationally accepted definition. Types of intervention: Treatment with plasma exchange alone or combined with steroids or immunosuppressive drugs. Types of outcome measures: PRIMARY OUTCOME MEASURE: ~bullet~patients treated for exacerbation: change in a specific muscle score after plasma exchange; ~bullet~patients treated for chronic myasthenia gravis: change in a functional scale. SECONDARY OUTCOME MEASURES: ~bullet~patients treated for exacerbation: change in a functional scale and percentage weaned from mechanical ventilation; ~bullet~patients treated for chronic myasthenia gravis: percentage in remission by the end of one year after first plasma exchange; ~bullet~adverse events. DATA COLLECTION AND ANALYSIS: One author extracted the data and the two others checked them. Since there was only one trial no formal meta-analysis was required. MAIN RESULTS: We identified one randomised controlled trial. Improvement in a quantitative muscle score was not significantly greater in patients treated with plasma exchange and prednisone than in patients treated with prednisone alone one month after onset of treatment. More relapses were observed in the plasma exchange and prednisone group in the first year as compared with the prednisone alone group. Problems in recruitment and matching of patients entered into this trial limit the conclusions that can be drawn. On the other hand,experience from many non-randomised studies suggests that plasma exchange is beneficial in myasthenia gravis. Consequently the relative benefits of plasma exchange are still unconfirmed. REVIEWER'S CONCLUSIONS: There are no adequate randomised controlled trials but many case series report short-term benefit from plasma exchange in myasthenia gravis, especially in myasthenic crisis. There are no adequate randomised controlled trials to determine whether plasma exchange improves the long-term outcome for myasthenia gravis. Further research is need to compare plasma exchange with alternative short-term treatments for myasthenic crisis and to determine the value of long-term plasma exchange for treating myasthenia gravis.
Combined Modality Therapy↗
Clinical and pathologic predictors of outcome in thymoma-associated myasthenia gravis.
BACKGROUND: Myasthenia gravis is by far the most common paraneoplastic syndrome of thymomas. There is little information regarding the influence of clinical variables and thymoma-associated factors on biologic development of myasthenia gravis. The aim of the study was to determine independent predictors of clinical outcome in thymoma with myasthenia gravis. METHODS: We studied 108 patients with thymoma-associated myasthenia gravis undergoing removal of the mediastinal mass between 1967 and 2000. Clinical and pathologic variables associated with clinical outcome of myasthenia were assessed by multivariate Cox regression analysis. RESULTS: Patients were followed for a mean period of 10 years (9 months to 33 years). A total of 38 patients died (35.2%), in 14 cases (37%) because of myasthenia gravis and in 6 (16%) because of recurrence of thymoma. With respect to clinical outcome of myasthenia gravis, at the end of the follow-up period, the rate of remission was 16% (n = 17). Of the 91 patients in whom remission was not achieved, 55 had no symptoms with immunosuppressive medication and 36 had symptoms with medication. CONCLUSIONS: In patients with thymoma-associated myasthenia gravis, well-differentiated thymic carcinoma (Müller-Hermelink system), age more than 55 years, and interval from the onset of symptoms to thymectomy of less than 1 year were found to be independent predictors of nonremission of myasthenia gravis after thymectomy.
Adolescent↗
Breathing pattern and central ventilatory drive in mild and moderate generalised myasthenia gravis.
BACKGROUND: Myasthenia gravis is a specific autoimmune disease characterised by weakness and fatigue. Respiratory muscle weakness has been studied using the determination of maximal respiratory pressures, but the response of respiratory centres is not well characterised. This study was undertaken to determine the breathing pattern and the central ventilatory drive in patients with mild and moderate generalised myasthenia gravis. METHODS: Twenty four patients with myasthenia gravis were studied, divided into two groups. Group 1 included 13 subjects (eight women and five men aged 23-64) with mild generalised myasthenia gravis, and group 2 was composed of 15 patients (11 women and four men aged 23-69) with moderate generalised myasthenia gravis. A control group comprised 15 healthy persons with a similar age and sex distribution. Spirometric measurements and maximal respiratory pressures were performed under basal conditions in all subjects, and the rate and depth of breathing and the inspiratory occlusion pressure in the mouth in the first 0.1 second (P0.1) were measured. RESULTS: No difference was detected for parameters of breathing pattern between patients in group 1 and control subjects, although P0.1 was higher in those in group 1. Subjects in group 2 had a lower tidal ventilation, shorter inspiratory time, and a higher frequency with a higher P0.1 than control subjects. CONCLUSIONS: Mild myasthenia gravis causes increased neuromuscular drive with a normal breathing pattern. Moderate myasthenia gravis is characterised by a more rapid shallow breathing pattern.
Adult↗
[Neonatal myasthenia gravis].
BACKGROUND: Myasthenia gravis, an autoimmune disease of young women, is due to the dysfunction of neuromuscular transmission. The newborn of a myasthenic mother inconstantly presents a transitory neonatal myasthenic syndrome. Maternal aggravation, or even myasthenic crisis with respiratory failure, can occur in the first three months post-partum. CASE REPORT: Mrs. S., para two without appreciable medical history, delivered normally a boy weighing 4 kg with an Apgar score of 10/10. At 3 h of life the newborn was admitted to the neonatal care unit for grunting and axial hypotonia. Diagnoses of maternal-fetal infection and fetal distress were excluded. The dissociated pattern of neurological disorders (refusal to drink, axial hypotonia, hypomimia, but good contact and normal alertness) led to search for neuromuscular causes or poison. Myasthenia gravis was then considered and confirmed by maternal electromyography, allowing the diagnosis of transient neonatal myasthenia gravis and early diagnosis and treatment of the maternal myasthenic crisis in a specialized care unit. The outcome of both mother and child was favorable under treatment. CONCLUSION: Lack of maternal myasthenia gravis history should not result in excluding the diagnosis of transitory neonatal myasthenia gravis when evocative neonatal neurological signs are present. The symptomatology in the newborn may indeed reveal maternal myasthenia gravis, allowing an early diagnosis in both the mother and the newborn.
Adult↗