Myasthenia gravis

Adult-onset myasthenia gravis is an acquired autoimmune disorder of neuromuscular transmission in which acetylcholine receptor antibodies attack the postsynaptic membrane of the neuromuscular junction. Although the cause of this disease is unknown, the role of immune responses in its pathogenesis is well established. Circulating acetylcholine receptor antibodies are present in 80% to 90% of patients with the generalized form of myasthenia gravis. Most patients have ptosis, diplopia, dysarthria and dysphagia. The weakness and fatigue worsen on exertion and improve with rest. Respiratory muscle and limb weakness are rare at the onset of the disease. For the past two decades, there has been considerable progress in understanding the diagnosis and management of myasthenia gravis. The diagnosis is based on clinical presentation, neurologic examination, and confirmation by means of electrophysiologic testing and immunologic studies. Myasthenia gravis mimics many neuromuscular diseases and even illnesses such as depression and chronic fatigue syndrome. One should always exclude drug-induced myasthenia gravis for all patients. With the introduction of new modalities of treatment, particularly immunosuppressive or immunomodulating drugs, plasma exchange and thymectomy, the morbidity and mortality of myasthenia gravis have decreased dramatically to the point that myasthenia gravis should not be considered as serious a disease as it once was. Although the several therapeutic options are usually effective and have meant independence in daily life to many patients with myasthenia gravis, well-designed, controlled, prospective studies are still lacking.     

Myasthenia gravis presenting as isolated respiratory failure

We present 2 cases of idiopathic CD4+ T-lymphocytopenia (ICL) in elderly patients. Case 1, a 73-year-old man, with pneumonia had received several antibiotics with unsuccessful results at another hospital. On admission, his CD4+ T-lymphocyte count was 109/microl and Pneumocystis carinii was detected by bronchoalveolar lavage fluid staining. No evidence of human immunodeficiency virus (HIV) infection was found. Despite therapy, the patient died of respiratory failure. Case 2, a 72-year-old man, contracted severe pneumonia, and Hemophillus influenzae was believed to be the pathogen. On admission, his CD4+ T-lymphocyte count was 238/microl. No evidence of HIV infection was found. He received antibiotics and improved successfully. We suggest that ICL may currently be incubating in a number of elderly pneumonia patients.     

Myasthenia gravis as a prototype autoimmune receptor disease

We recorded full-field electroretinograms before and after vitrectomy in 18 eyes of 18 patients with idiopathic macular hole. The results were compared between affected and fellow eyes in the preoperative and early (within 10 days) and late (3 to 6 months) postoperative periods. No significant changes between affected and control eyes were found in the amplitude of the rod electroretinogram, mixed cone-rod electroretinogram, cone electroretinogram a- and b-waves or 30-Hz flicker electroretinogram in all stages of the study. The peak implicit times of the cone electroretinogram (a- and b-wave) and dark- and light- adapted oscillatory potential (O1-O4), however, were delayed. Also, the amplitude of the oscillatory potentials (O1+O2+O3+O4) was significantly reduced in the early postoperative period. By the late period, all of these changes had resolved. We concluded that electrophysiologic changes were derived from a transitory dysfunction of the inner retina. The possible causes of the electroretinographic changes would include mechanical trauma of the surgery, intravitreous air tamponade or the changes in vitreous electrolytes after surgery. Oscillatory potentials were more sensitive than a- and b-waves in eliciting dysfunction of the inner retina in operate on eyes.     

Myasthenia gravis in old age. A retrospective study of 58 patients

The course in 58 cases of myasthenia gravis in subjects over 50 years of age is reported. They total about 30% of cases in all age-groups. 36.2% of the patients died after an average period of illness of 3.4 years. 58.6% initially showed only ocular symptoms and in 58.8% of these the myasthenia was likewise located only in the eyes in the further course of the illness. The prognosis of ocular myasthenia is very good if the myasthenic process does not extend to other muscle groups in the first or second year of illness. 41.2% of primary ocular myasthenia turned into other types, in most cases a generalized type, and these had a poor prognosis. 69.2% of these patients died after an average period of illness of 1.5 years due to myasthenia-induced complications. Cases of myasthenia which initially are of the generalized type, in which the average duration is only 2.7 years until death, and to some extent the bulbar types, also have a poor prognosis. Ocular myasthenic cases generally need only small doses of cholinesterase inhibitors. Some patients had no medical treatment because there was no subjective or objective need for it. Several patients were given doses of cholinesterase inhibitors which were too large; excessive doses are to be avoided because of the proven negative influence of cholinesterase inhibitors on the myoneural system. It is recommended that types of myasthenia with a poor prognosis be treated early with corticoids, ACTH or azathioprin, if the cholinesterase inhibitors have proved ineffective or it their effect is unsatisfactory. Thymectomy is advisable only in patients under 60 years of age.     

Myasthenia gravis and primary squamous cell carcinoma of the thymus

Occurrence of primary squamous cell carcinoma of the thymus gland in a 65-year-old man with myasthenia gravis is reported. Histologic and immunohistochemical studies confirmed the diagnosis of a differentiated squamous cell carcinoma. Extensive clinical investigations ruled out another primary site for the tumor. The patient made a full recovery postoperatively. Only three cases of primary squamous cell carcinoma of the thymus gland in association with myasthenia gravis have been reported in the literature.     

Myasthenia gravis associated with small-cell carcinoma of the lung

A 49-year-old man complained of a 3-month history of progressive generalized muscle weakness. He was diagnosed as having small-cell lung carcinoma at the same time. He received an intravenous injection of edrophonium chloride with remarkable improvement of muscle strength. Electromyographic studies revealed a compound muscle action potential that decreased after repetitive stimulation. These findings were considered representative of myasthenia gravis (MG), and inconsistent with Eaton-Lambert syndrome. The appearance of MG with small-cell lung carcinoma seems to be very rare, but possible.     

Myasthenia gravis after allogeneic bone marrow transplantation. A case report and a review of the literature

PURPOSE: The treatment of infant acute lymphoblastic leukemia (ALL) continues to be a significant challenge for pediatric oncologists due to the high incidence of early relapses. Salvage regimens used to date have met limited success. We describe two cases of relapsed infant ALL who have achieved long-term survival with an intensive antimetabolite-based salvage regimen. PATIENTS AND METHODS: Two consecutive infants with relapsed ALL presented at our institution and were treated with an antimetabolite-based regimen. Both cases exhibited clinical and biological phenotypes previously associated with infantile ALL. RESULTS: Both patients have achieved prolonged and sustained remissions 48 and 30 months EFS respectively following therapy with intensive antimetabolite-based salvage regimen. CONCLUSIONS: An intensive multiagent antimetabolite based salvage regimen resulted in prolonged EFS in two cases of relapsed infant ALL. Dose intensification was achieved by administering repeated cycles of the same treatment schema using high dose chemotherapy throughout therapy. These infants were spared prophylactic cranial irradiation without a negative impact on outcome. The use of L-asparaginase, timed after high-dose Cytarabine (ARA-C) throughout therapy, might have contributed to their cure.     

Myasthenia gravis: another autoimmune disease associated with hepatitis C virus infection

We report on a male Egyptian patient who developed myasthenia gravis with typical symptoms, beneficial response to pyridostigmine, and the presence of anti-acetylcholine receptor antibodies and anti-striated muscle antibodies during the course of a chronic hepatitis C infection complicated by liver cirrhosis. As also reported for the herpes simplex and for the HIV virus, hepatitis C may lead to myasthenia gravis via a mechanism of cross-reactivity between viral epitopes and the acetylcholine receptor.     

Myasthenia gravis: recognition of a human autoantigen at the molecular level

The symptoms of myasthenia gravis are primarily or exclusively due to an autoimmune response against the muscle nicotinic acetylcholine receptor (AChR) and this has been the object of intensive investigations for almost 20 years. A detailed picture at the molecular level of the interaction of this autoantigen with the key elements involved in the autoimmune response, such as anti-AChR antibodies, the T-cell receptor and restricting major histocompatibility complex molecules, is now emerging for both human myasthenia gravis and its experimental model, experimental autoimmune myasthenia gravis. Here, Maria Pia Protti and colleagues focus on the molecular interactions occurring in human myasthenia gravis and summarize recent information on pathogenic mechanisms of the autoimmune response, and the structure of epitopes recognized by B cells and CD4+ T cells of myasthenic patients on the AChR molecule.     

A randomized double-blind trial of prednisolone alone or with azathioprine in myasthenia gravis. Myasthenia Gravis Study Group

Noninvasive alternatives to esophageal pressure (Pes) are needed to evaluate respiratory effort during sleep. Pulse transit time (PTT) is the time taken for pulse pressure to travel from the aortic valve to the periphery. PTT has been shown to be inversely correlated with blood pressure, and can reveal acute changes generated by high pleural pressure swings during pulsus paradoxus. A close relationship has been demonstrated between the increase in Pes and a progressive rise in the amplitude of PTT oscillations. The aim of the present study was to assess the accuracy of PTT for the classification of sleep respiratory events as central or obstructive. Respiratory events occurring during sleep were randomly chosen from 13 unselected male patients (mean apnea-hypopnea index [AHI] = 25.1 per hour of sleep; age = 47.3 yr, body mass index [BMI] = 27.1 kg/m2). Two observers experienced in polysomnography classified 177 events on the basis of the "gold standard method": the measurement of Pes. For 167 events about which the observers agreed, the PTT signal was analyzed visually and independently by the two observers blinded to Pes, in order to reclassify the same sleep respiratory events. The two observers were in agreement for 94.6% of the events scored visually on PTT recordings. We evaluated sensitivity (Se) (Observer 1: 94%, Observer 2: 91%), specificity (Sp) (97% and 95%, respectively), negative predictive value (NPV) (95% and 92%, respectively), and positive predictive value (PPV) (96% and 94%, respectively), of PTT with Pes as the reference. Misclassifications of respiratory episodes were usually due to artifacts or baseline variations of the PTT signal (57%), and occurred during rapid eye movement (REM) sleep (42.8%). PTT has shown a high sensitivity and specificity in differentiating obstructive and central respiratory events, and may become the reference noninvasive tool for this purpose.     

Myasthenia gravis: pathogenesis and therapeutic approach on the basis of molecular structure and immunogenicity of acetylcholine receptor

Recent research for myasthenia gravis has been advanced by the availability of primary sequence of acetylcholine receptor (AChR) precursor and AChR transmembrane topography. (1) Synthetic peptides of AChR alpha-subunit defined myasthenogenic sites recognized by blocking or modulating antibody; their capability of inducing an animal model suggests that synthetic antigens contain not only B-cell sites but also T-cell sites which interact with restricted MHC class II molecules. (2) In view of the conformation-dependent B-cell site expected at beta-turn and the MHC-restricted T-cell site expected at amphipathic alpha-helix, conformationally modified peptides were synthesized by linking them; some were in combination with artificially sequenced peptide to favor an enhanced beta-turn. (3) Experiments by the use of these synthetic peptides demonstrated that such antigens were enhanced in myasthenogenicity. However, the immunogenic conformation for the induction of animal model did not necessarily assume that for the detection of antibody in native AChR-immunized rats. (4) Peptides synthesized to assume specifically for binding with antibody were used as a tool for immunoadsorption via plasma perfusion in myasthenic patients, resulting in clinical improvement.     

Familial myasthenia gravis. Report of four cases

Total entry rate of blood glucose and the rate of irreversible loss of blood acetate and its oxidation have been examined in sheep at rest and while walking on a horizontal treadmill at 5 km/h for 2 h. Sheep were given their daily ration of 1000 g chaff in 24 eaual portions at hourly intervals and received multiple intravenous injections of [2-3H]glucose and intravenous infusions of [1-14C]acetate and NaH14CO3. At rest the total entry rate of blood glucose was 0-44 +/- 0-03 mmol/min (values given as mean +/- s.e.m. for four sheep), the glucose pool was 23 +/- 1 mmol and the rate of irreversible loss of blood acetate was 2-3 +/- 0-1 mmol/min. During exercise, the total entry rate of blood glucose was 0-84 +/- 0-04 mmol/min, the glucose pool was 27 +/- 2 mmol and the rate of irreversible loss of blood acetate was 2-6 +/- 0-1 mmol/min. Gluconeogenesis apparently increased markedly in response to exercise as indicated by the incorporation of 14C from blood bicarbonate into blood glucose. Despite the substantial increase in the rate of irreversible loss of blood bicarbonate (from 11-6 +/- 1 to 20-2 +/- 2 mmol C/min), and hence energy expenditure with exercise, only a slight change was recorded in the proportion of the irreversible loss rate of acetate that was oxidized.     

Myasthenia in an epileptic patient

The author described a case of myasthenia and epilepsy in a female aged 36 years. The relationship between myasthenia and epilepsy was discussed. The additional factor which made the diagnosis difficult is bilateral deafness.     

Rapid eye movements in myasthenia gravis. II. Electro-oculographic analysis

Voluntary saccades were studied by electro-oculography in ten patients with myasthenia gravis (MG) and in eight patients with other types of ophthalmoplegia. Despite limited range of eye movements, maximum velocities of 20 degree and 40 degree saccades in patients with MG were not significantly different from those in normal individuals, whereas maximum velocities in patients with other types of ophthalmoplegia were significantly decreased. In some myasthenic patients, small amplitude saccades were hypermetric and had high velocities, appearing clinically as "quiver" movements characteristic of MG. In MG the preservation of saccades with high initial velocities, even in the presence of severe ophthalmoplegia, suggests that muscle fibers generating rapid movements during saccades (twitch fibers) can be relatively spared when muscle fibers responsible for maintenance of excentric gaze (tonic fibers) are severely affected.     

Acquired myasthenia gravis

Myasthenia gravis, an antibody-mediated disorder of neuromuscular transmission that produces clinical weakness, may be ocular or generalized. Clinical diagnostic evaluation may be supplemented by electrophysiologic studies and antibody testing. Therapeutic options, including anticholinesterase inhibitors, immunosuppressive agents, plasmapheresis and thymectomy, are tailored for the individual patient. This article emphasizes the key aspects of the clinical evaluation, diagnosis, and therapy.