A case of Lambert-Eaton myasthenic syndrome with possible myasthenia gravis

Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder of neuromuscular transmission (NMJ) that shares many clinical features with myasthenia gravis (MG). We report a 73 year-old lady who presented 10 years previously with stiffness of both calves, dry mouth, fatigue, proximal weakness and areflexia in lower limbs. Neurophysiological studies were consistent with LEMS. Her work up for an underlying neoplasm was negative. She recently developed unilateral ptosis and diplopia which dramatically improved with pyridostigmine suggesting concomitant MG.     

A case of myasthenia gravis proven by ultrastructural study

Although light microscopic features of muscle are not pathognomonic in most cases of myasthenia gravis (MG), careful examination of neuromuscular junction by electron microscopy (EM) can reveal important clues for this disease. We report here a case of MG confirmed by EM study to emphasize that tissue diagnosis is still the best adjuvant to confirm the diagnosis. An 18-year-old female visited our hospital complaining of progressive muscle weakness for 3 years. She had difficulty in running, going upstairs and doing routine activities. Symptoms were aggravated with continuous work and resolved after rest. She had weakness of bilateral masseter and facial muscles and proximal portions of extremities without definite diurnal variation. Electromyography showed myopathic changes in proximal muscles of extremities. MG was considered but tensilon test was equivocal. Repetitive nerve stimulation tests revealed 20-30 percent decrease in responses to low and high rate stimulation. Muscle biopsy revealed selective type 2 atrophy. Ultrastructurally, abnormalities of neuromuscular junctions, i.e., wide primary synaptic cleft, and wide and shallow secondary synaptic clefts with mild myopathic features were present. These findings were pathognomonic for MG. Later, her symptoms were improved completely 3 months after thymectomy. The histologic finding of thymus was follicular hyperplasia.     

The immunological effects of thymectomy in myasthenia gravis.

Thymus-derived (T) lymphocytes in the peripheral blood and cellular immune function have been studied in ten patients with myasthenia gravis and in fifteen different myasthenic patients more than 10 years after thymectomy. The results were compared with those of a normal control population. The non-thymectomized myasthenic patients had normal T lymphocyte concentrations measured by rosetting with native sheep red cells. These patients also showed normal sensitization and recall of delayed hypersensitivity, phytohaemagglutinin (PHA) induced lymphocyte transformation and antibody-assisted (K cell) cytotoxicity; however, PHA-induced cytotoxicity was markedly reduced (P less than 0.001). The thymectomized group exhibited a lower mean percentage and absolute number of E-rosette-forming cells, which returned toward normal after in vitro treatment with thymosin. PHA-induced lymphocyte cytotoxicity, however, was normal in the patients who had undergone thymectomy, as were lymphocyte transformation, antibody-assisted cytotoxicity and sensitization to dinitrochlorobenzene (DNCB); there was a decrease in recall of established delayed hypersensitivity. Adult thymectomy in man, therefore, produces a partial and dissociated decrease in T cell responses and it is unlikely that the beneficial effect of this operation in myasthenia gravis is related to immunosuppression.     

Fetal alcohol syndrome and myasthenia gravis

Alcohol is increasingly being described in the literature as a teratogenic agent producing dysmorphism and multisystem problems. The child described herein demonstrates the occurrence of myasthenia gravis and mitral incompetence with fetal alcohol syndrome. The association of myasthenia gravis in this case is unique, and could be suggestive of an immunological component to this syndrome.     

Isaac's syndrome associated with myasthenia gravis and thymoma

A 65-year-old male developed fatigable weakness of ocular and bulbar muscle and positive anti-acetyl cholinesterase antibodies suggesting the diagnosis of myasthenia gravis. His condition responded to anticholinesterase and immunotherapy. However, 18 months later, he developed painful paresthesiae, muscle cramps with hyperhiderosis, and was diagnosed as having Isaac's syndrome (neuromyotonia, continuous muscle fibre activity). Computed tomography of the chest revealed a thymic mass, which was confirmed after surgery and histopathology as thymic cell carcinoma. The co-occurrence of myasthenia gravis and continuous muscle fiber activity should prompt the consideration of the occurrence of these disorders as one of the paraneoplastic manifestations, most often due to a thymic neoplasm. Both these conditions respond to treatment of underlying thymoma. This case is a very rare presentation worth reporting.     

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.     

Pathogenesis of myasthenia gravis

 Various studies over the last 25 years in Man and animal models have revealed many steps in the pathogenesis of myasthenia gravis (MG) which is now considered the classical organ specific, autoantibody mediated and T cell dependent human autoimmune disease. Though not a disease entity, MG is associated with pathological alterations of the thymus in about 80% of cases. These are described here with reference to distinct models of autoimmunization against the acetylcholine receptor (AChR). In MG with thymitis, intrathymic production of AChR-specific autoantibodies is the result of a classical antigen-driven immune reaction that occurs completely inside the thymus and probably involves AChR on myoid cells as the triggering (myasthenogenic) antigen. Genetic factors contribute essentially to the pathogenesis of this form of MG. In thymoma-associated MG genetic factors are probably of marginal significance. Neither intratumour autoantibody production nor T cell activation seem to occur and the AChR is not the myasthenogenic antigen. Instead, abnormal neurofilaments that share epitopes with the AChR and other autoantigen targets in paraneoplastic MG are expressed in thymomas and may trigger autoantigen-specific, non-tolerogenic T cell selection by molecular mimicry. These data support the hypothesis that initial steps in the pathogenesis of most MG cases take place within abnormal thymic microenvironments, be they inflammatory or neoplastic. Where these initial steps occur in MG cases without thymic pathology is not known. Likewise, the factors involved in the initial triggering of MG remain enigmatic in all MG subtypes. Received: 16 September 1996 / Accepted: 28 October 1996     

A membrane-associated autoantibody in a case of myasthenia gravis with chronic hepatitis.

A new antibody reacting with a cell membrane-related antigen is described in a patient with myasthenia gravis and chronic liver disease. The antibody gave a striking peripheral immunofluorescence in all cells tested and did not react with smooth muscle fibres, being distinct from anti-actin and anti-myosin antibodies. The antigen was widely distributed in human and animal tissues. The exact relationship of this antibody to the clinical condition is not obvious but its presence is further evidence of widespread disturbances of humoral immunity in myasthenia gravis.     

Misdiagnosis of myasthenia gravis

Patients with myasthenia gravis (MG) are too often misdiagnosed as having another disorder. Three patients are presented who were thought to have amyotrophic lateral sclerosis, velopharyngeal incompetence, and no diagnosis of MG, but actually each had myasthenia gravis. Their histories illustrate how the diagnosis of myasthenia gravis can be easily missed.     

Autoantibodies in d-penicillamine-induced myasthenia gravis: A comparison with idiopathic myasthenia and rheumatoid arthritis

The distribution of autoantibodies was studied in patients with rheumatoid arthritis (RA) treated by d-penicillamine and who developed myasthenia gravis (MG). The anti-human acetylcholine receptor (AChR) antibodies were specifically associated with clinical symptoms of MG without any difference in the pattern of specificities in idiopathic (id-MG) or in induced MG (DPen-MG). Conversely, anti-nuclear antibodies were elevated in DPen-MG sera compared to id-MG sera (P < 0.001) but were also compared to patients with RA treated by d-penicillamine (or thiopronine) and who did not develop MG. Anti-denatured DNA antibodies were enhanced in sera from treated patients, whether they had presented or not a MG disease. Anti-histone antibodies were associated with RA. These observations suggest that the immunological imbalance in RA patients, can be increased by a drug treatment which may trigger the appearance of a second autoimmune disease such as MG, where anti-AChR antibodies are associated with anti-nuclear antibodies.     

血气监测指导药物滴定治疗重症肌无力危象1例

重症肌无力 （Myasthenia Gravis,MG） 是一种以神经肌肉接头处突触后膜功能障碍为特征的自身免疫性疾病, 该病以肌肉疲劳和无力为特征,其主要抗原靶点为乙酰胆碱受体 （Acetylcholine Receptor,AChR）。当累及膈肌等呼吸肌引起呼吸衰竭需要有创或无创通气时称之为肌无力危象 （Myasthenic Crisis,MC）,通气不足引起CO₂大量潴留、PCO₂升高及颅内压升高,进而导致意识障碍。因此,及时监测动态血气并采取精确治疗显得尤为重要。滴定抗胆碱酯酶剂治疗的目的是为药物转化提供合适的剂量,处理好“剂末现象”,为危象患者呼吸功能好转后提供更好的脱机条件。本文报道1例因感染引起吞咽困难、呼吸困难及意识障碍的抗AChR抗体阳性的重症肌无力危象患者,经动态监测血气、呼吸机辅助通气、控制感染及滴定抗胆碱酯酶药物治疗后好转出院。     

Poly-autoimmunity in patients with myasthenia gravis: A single-center experience

Abstract

We evaluated the co-occurrence of autoimmune diseases (ADs) in a large population of myasthenia gravis (MG) patients from a single center. Our survey included 984 patients, 904 with anti-acetylcholine receptor antibodies and 80 with anti-muscle specific kinase antibodies. The anti-acetylcholine receptor positive population included patients with early-onset (age at onset ≤50 years), late-onset and thymoma-associated disease. Follow-up ranged 2–40 years. Two-hundred and fourteen ADs were diagnosed in 185 patients; 26 of them had two or more ADs in association with MG. Thyroid disorders were the most common and, together with vitiligo and thrombocytopenia, occurred in all disease subsets. Otherwise, there was a broad variability with partial overlap among patient groups. The highest rate of ADs was observed in early-onset patients, while clusters, i.e. 2 or more ADs other than MG in the same individual, were more common among thymoma cases. Thirty-four diseases were diagnosed at the same time, 88 occurred before and 92 after the onset of MG. On multivariate analysis, immunosuppressive treatment was the only independent variable which negatively influenced the risk of developing other ADs in our cohort.     

Treatment of experimental myasthenia gravis with cyclosporin A

Cyclosporin A (CsA) is an immunosuppressive agent that has recently been used to prevent rejection of transplanted tissues. The effects of CsA treatment of rats with experimental autoimmune myasthenia gravis (EAMG), an antibody-mediated autoimmune disorder of acetylcholine receptors (AChRs) at neuromuscular junctions, have been studied. CsA treatment at the time of primary immunization suppressed the antibody responses to AChR virtually completely. Following 12 weeks of CsA, the AChR-immunized rats responded like naive controls to a further challenge of AChR. Treatment of ongoing EAMG resulted in a reduction of AChR antibody by more than 50%. The secondary response to a challenge of AChR was prevented by CsA treatment, but a very large challenge dose in adjuvant partially overwhelmed the effect of CsA. CsA treatment also prevented the loss of AChRs at neuromuscular junctions, as compared with untreated EAMG controls (P less than 0.02). The efficacy of CsA in suppressing ongoing and secondary hetero- and autoimmune responses against AChR in EAMG encourages its ultimate application in autoimmune diseases of man, such as MG. Its usefulness will depend on the ability to determine effective doses of CsA that are well tolerated.