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Myasthenia gravis is characterised by muscle weakness and fatigability, particularly of the facial and extremity muscles, deteriorating during the day. During pregnancy, myasthenia gravis is rare and the course of illness is unpredictable. The present case illustrates that first diagnosed during pregnancy, recurrent exacerbations can appear and lead to life-threatening situations.
Myasthenia gravis is a chronic neuromuscular disease characterized by muscular weakness and fatigability. Dental management of patients diagnosed with myasthenia gravis presents a challenge to the dental profession. A MEDLINE search of the English medical (limited to provision in dental care) and dental literature on myasthenia gravis and dental management published between 1975 and 2004 was conducted. In the dental literature, 12 articles were found, and only a few focused on myasthenia gravis and dental care. The purpose of this article was to review and summarize the clinical signs and symptoms associated with myasthenia gravis, highlighting the role of the dental profession in the process of the diagnosis and management of the oral and dental complications that might be associated with the disease, while avoiding myasthenic crisis.
Transient neonatal myasthenia gravis is a postsynaptic neuromuscular transmission defect occurring in 21% of infants born to women with active (and, less commonly, in remission) acquired myasthenia gravis. Although passive-transfer acetylcholine receptor (AChR) antibodies are found in the majority of these newborns, their pathogenic role is questionable because only some infants are symptomatic. Pathogenesis in infants without AChR antibodies is unknown. There is still no biologic marker for prenatal identification of this subpopulation of newborns, although HLA typing may be a promising tool. Sucking, swallowing, and respiratory difficulties are the most common presenting signs in the first day of life. Final diagnosis is done when administration of acetylcholinesterase agents transiently corrects the neuromuscular transmission defect. Serum AChR antibody titers follow the same pattern as their mothers. Supportive management and anticholinesterase agents prior to feedings are necessary in about 80% of patients. In the majority of infants the condition resolves spontaneously.
Experimental autoimmune myasthenia gravis (EAMG) is caused by autoantibodies against the nicotinic acetylcholine receptor (AChR) at the neuromuscular postsynaptic membrane and represents an animal model of myasthenia gravis in human. Recent studies highlighted the roles of TH1 cytokines (IFN-gamma, IL-12), rather than TH2 cytokines (IL-4), in the pathogenesis of EAMG by using homozygous (-/-) knockout mice with an EAMG-susceptible genetic background. To further evaluate a role for IFN-gamma, we injected recombinant rat IFN-gamma (rrIFN-gamma) at the time of immunization with AChR in complete Freund's adjuvant to EAMG-susceptible Lewis rats and EAMG-resistant Wistar Furth (WF) rats. RrIFN-gamma enhanced Lewis rat EAMG. The exacerbated muscular weakness was associated with higher levels of anti-AChR IgG and enhanced TNF-alpha responses. Anti-AChR IgG antibody levels were augmented to a similar extent as in Lewis rats, however, the identical immunization and IFN-gamma injection induced only mild and transient EAMG in WF rats due to the default TH3 phenotype development and inherent low TH1 responses. We conclude that IFN-gamma plays a major role in the pathogenesis of EAMG in the Lewis rat, but fails to break disease resistance in the WF rat.
Hybridomas secreting monoclonal antibodies directed against the nicotinic acetylcholine receptor have been developed from rats with experimental autoimmune myasthenia gravis and from a patient with myasthenia gravis. Rat monoclonal antibodies were characterized by their ability to bind to electroblotted acetylcholine receptor subunits. Of 34 tested, 22 bound to the alpha subunit. Three bound to other subunits, and the remainder appeared to bind only to the native molecule. The human monoclonal antibodies were analyzed with respect to their binding to membrane-bound and solubilized acetylcholine receptor. Many bound with greater affinity to the membrane-bound form of the antigen. Two rat monoclonal antibodies capable of passively transferring experimental autoimmune myasthenia gravis, and with reactivities to the alpha subunit of the acetylcholine receptor, were employed to produce isogeneic monoclonal antiidiotypic antibodies. When they were injected prior to immunization with acetylcholine receptor, two of the antiidiotypic antibodies directed against framework determinants prevented the development of experimental autoimmune myasthenia gravis. This observation raises the possibility that the human monoclonal antibodies will be useful in the development of idiotypic treatment of the human disease.
Acquired myasthenia gravis was diagnosed in 6 Newfoundlands from 2 distinct lineages. Three dogs, including 1 pair of littermates, from each lineage were affected. History and clinical signs did not differ from that reported for other dogs with acquired myasthenia gravis. Although a genetic predisposition for development of certain autoimmune diseases in several species has been identified, the immunopathogenesis of myasthenia gravis is multifactorial and includes hormonal, environmental, and infectious disease factors. The high incidence of myasthenia gravis in these 2 distinct lineages of Newfoundlands, a breed with a low relative risk for development of this disease, suggests an underlying genetic mechanism. However, mode of inheritance could not be determined from this small number of dogs. Regardless, breeders should be alerted to this disorder, and they should consider removing Newfoundlands with acquired myasthenia gravis from breeding programs.
Myasthenia gravis is an acquired disorder of the neuromuscular junction characterised by fatiguable weakness of the limbs, bulbar and facial muscles and may be complicated by respiratory muscle weakness and failure. One often confirms the diagnosis by a simple serological test looking for the presence of the nicotinic acetylcholine receptor antibody. However, seronegative myasthenia constitutes about 20% of cases and in the case of ocular myasthenia, only 50% will have the antibody. Therefore, the diagnosis can be less than straightforward especially if the patient presents with vague symptoms such as fatigue or presents to specialities other than neurology or ophthalmology. The fact that the diagnosis may prove to be challenging, compounded by the fact that the condition is relatively rare and that the antibody to the acetylcholine receptor is not always present, epidemiological data is often less than precise and indeed difficult to acquire. We felt it was necessary to try to establish the epidemiological data on seropositive myasthenia gravis in Tayside, (this has never been carried out) bearing in mind the above pitfalls, and see how the incidence compares with similar and previous studies.
Myasthenia gravis and pemphigus are both considered to have an autoimmune basis. Although immunological and clinical studies have been performed on large numbers of patients with myasthenia gravis, the coexistence of myasthenia gravis and pemphigus foliaceus has rarely been described. We recently have the opportunity to study a 33-year-old female patient having both of these autoimmune diseases confirmed by various diagnostic methods. This rare coexistence of myasthenia gravis and pemphigus foliaceus has not been previously documented in Korea.
Familial Autoimmune Myasthenia Gravis (FAMG) is rarely reported. We present a mother and son with late-onset mild to moderate ocular disease, low acetylcholine receptor antibody titre and the absence of a thymoma. Both responded well to low doses of anticholinesterase. HLA typing revealed that they did not share the usual HLA antigens or haplotypes with that previously reported in Caucasian and Chinese sporadic Myasthenia Gravis. Chinese FAMG may be associated with HLA antigens different from that of sporadic MG.
Myasthenia gravis is an autoimmune disease that is associated with antibodies to acetylcholine receptors. It is associated with other autoimmune diseases such as thyroiditis (10%), systemic lupus erythematosus (2-8%), rheumatoid arthritis (4-7%), Sjögren's syndrome and polymyositis. It is not commonly found with scleroderma. We describe a case of scleroderma developing in a patient 6 years after the onset of myasthenia gravis. HLA-B8/DR3 may play a role in the association of the 2 conditions.
Experimental autoimmune myasthenia gravis (EAMG) is induced by a single injection of acetylcholine receptor (AChR) with complete Freund's adjuvant and represents a useful animal model for studying the mechanisms by which autoimmune responses to AChR and its subunits are coupled to the development of human myasthenia gravis. Using an immunospot assay, we enumerated cells secreting IgG antibodies against Torpedo AChR and the alpha-, beta-, gamma- and delta-subunits of Torpedo AChR in lymph nodes, spleen and thymus from Lewis rats over the course of EAMG. Cells secreting IgG antibodies to AChR and to all four subunits were detected at higher numbers in the three immune organs in EAMG compared to controls. Numbers were highest in lymph nodes followed by spleen and thymus. Cells secreting IgG antibodies against native AChR were always higher than those against individual subunits. The immunogenicity between the four subunits did not differ, with the exception that the alpha-subunit induced a slightly higher B cell response in thymus and lymph nodes. The patterns of B cell responses were similar when analyzed over the course of EAMG from week 2 to week 5, and there was no restriction of the B cell repertoire early in EAMG. Anti-AChR and anti-subunit antibody-secreting cells were also detected in control animals immunized with adjuvant only, but at numbers which were much lower, and which were within the same level as numbers of cells secreting IgG antibodies to the control antigen myelin basic protein, probably reflecting naturally occurring autoimmune B cells.
Studies in myasthenia gravis (MG) patients demonstrate that polymorphism at the HLA-DQ locus influences the development of MG. Several studies using the mouse models also demonstrate the influence of class II molecules, especially the H2-A, which is the mouse homologue of HLA-DQ, in experimental autoimmune myasthenia gravis (EAMG). We used transgenic mice expressing two different DQ molecules, DQ8 (DQA1*0301/B1*0302) and DQ6 (DQA1*0103/B1*0601), to evaluate the role of HLA-DQ genes in MG. These mice do not express endogenous mouse class II molecules since they contain the mutant H2-A beta0 gene. The mice were immunized with Torpedo acetylcholine receptor, and EAMG was assessed by clinical evaluation and was confirmed by electrophysiology. Clinical scores for EAMG were highest in HLA-DQ8 transgenic mice, whereas the scores of HLA-DQ6 mice rarely exceeded grade 1. There was no incidence of EAMG in class II-deficient (H2-A beta0) mice. These results demonstrate that polymorphism at the HLA-DQ locus affects the incidence and the severity of EAMG. The manifestation of susceptibility to EAMG in the context of human class II molecules underscores the important roles of these molecules in the initiation and perpetuation of EAMG.
Myasthenia gravis is rare in childhood. In the last 12 years, we have treated eight children under 16 years of age for this disease. There were six girls and two boys, a ratio of 3:1. Age of presentation of symptoms ranged from 10 to 16 years (mean 11 3/4). There was no significant family history and there were no significant associated diseases. Antibodies were measured in six patients and were all negative. All patients were given cholinergic drugs and five had corticosteroids as well. Three underwent tracheostomies because of severe respiratory insufficiency. There was clinical deterioration or no improvement in spite of increasing doses of medication; hence, thymectomy was performed in all after an average duration of symptoms of 12 months (range 4 to 17). All thymectomies were done through median sternotomy. There was no postoperative morbidity or mortality. No thymoma was found. Four had lymphoid hyperplasia, in three, the thymus looked normal and in one it looked very atrophic. Dramatic amelioration with eventual complete recovery was seen in six, with an average follow-up of 7.3 years (3 to 11) after thymectomy. Two patients are only one year after thymectomy and are improving progressively. We recommend early thymectomy in myasthenia gravis of childhood on the basis of very encouraging results.
Experimental autoimmune myasthenia gravis (EAMG) was studied in 39 rabbits which were repeatedly immunized with purified membrane-bound Torpedo (Nacine timilei) acetylcholine receptor (N-AchR). These rabbits invariably formed anti-AChR antibodies and some of them developed muscular weakness or flaccid paralysis. Pharmacological, physiological and ultrastructural studies showed that the pathological features of EAMG in rabbits closely resembled those of human myasthenia gravis. Antibody titer to AChR of the rabbit sera was determined with ELISA. In some of the rabbits, a rise in antibody Level occurred without appearance of weakness, while it is still likely that AChR antibody could be necessary for the induction of neuromuscular blockage. The sensitivity to curare was found to correlates closely with the severity of the disease. Typical electromyographic changes were found only in some of the EAMG rabbits with these studies. It was considered that anti-AChR concentration would not be the single pathological factor in EAMG.
Twenty four myasthenia gravis patients, 14 females and 10 males, aged between 5 and 65 years (average 29) were studied electrocardiographically. The abnormalities found in the ECG were: prolonged "Q-T" intervals (10 cases, 44.1%), sinus tachycardias (5 cases, 20.8%), sinus arrhythmias (5 cases, 20.8%), right bundle branch block (4 cases, 16.6%), and non-specific "T" wave changes (2 cases, 8.3%). Among our 24 patients with myasthenia gravis, in contrast to previous reports, only two had non-specific "T" wave abnormalities. But prolonged "Q-T" intervals, right bundle branch block, sinus tachycardias and sinus arrhythmias, when compared to normal population incidence, were found to be quite significant. In pathogenesis, primary myocardial histo-pathological abnormalities, and the role of extracardiac factors in producing the changes were discussed.
Patients with myasthenia gravis undergo lifelong treatment with anticholinesterase agents. While the heart is usually unaffected by this disease, clinicians should bear in mind the potential adverse interaction between cardiac function and the underlying myasthenic disease or its specific medications. In the present article we report, to the best of our knowledge for the first time in the literature, a case of vasospastic acute myocardial infarction due to iatrogenic hypercholinergic crisis secondary to anticholinesterase therapy in an elderly female with myasthenia gravis. This clinical vignette emphasizes the importance of taking into account the potential vasospastic effect of anticholinesterase drugs. Indeed, prompt recognition of the pathophysiology of myocardial ischemia due to iatrogenic hypercholinergic crisis is pivotal to the timely and appropriate management of this medical emergency, as well as prevention of future recurrences.
Human autoimmune myasthenia gravis (MG) is associated with the IL-1beta TaqI RFLP allele 2. Individuals positive for this allele have high levels of inducible IL-1beta in their peripheral blood. Here, we have characterized MG induction and the immune response elicited by Torpedo acetylcholine receptor (AChR) immunization in wild-type and IL-1beta deficient (-/-) mice. Compared with wild-type mice, IL-1beta-/- mice were relatively resistant to induction of clinical experimental autoimmune myasthenia gravis (EAMG). Draining lymph node cells from IL-1beta-/- mice showed poor proliferative capacity upon AChR stimulation in vitro. Both Th1 (IFN-gamma, IL-2) and Th2 (IL-4) cytokine responses were reduced and levels of serum anti-AChR antibodies decreased in IL-1beta-/- mice compared to wild-type mice. Taken together, these results reveal a critical role for IL-1beta in the induction of MG in mice, and support a role for IL-1beta in the pathogenesis of MG in man.
Myasthenia gravis is considered to be an autoimmune disorder of neuromuscular transmission. Thymectomy is an effective mode of treatment which produces either remission or stabilization of symptoms especially in young female patients with short duration of disease. The present study, records the experience in ten pediatric patients with early thymectomy done via the transcervical approach. There were no operative deaths or serious complications. Follow-up for a mean of 37 months has shown one to be in complete remission requiring no medication and eight to have improved or stable symptoms. Thymectomy via the transcervical approach is an effective mode of treatment for patients with myasthenia gravis. Since this approach involves a small dissection and avoids sternotomy, the transcervical approach results in a very short postoperative recovery period. It is ideal for those patients not in respiratory failure. It can also be safely done in patients requiring intubation for acute respiratory failure preoperatively.