Myasthenia gravis: lung-function studies without and with edrophonium chloride.

25 myasthenia gravis-afflicted patients (14 crisis-endangered and 11 not endangered) were investigated with respect to their respiratory function and reaction of the respiratory parameters to Tensilon (edrophonium chloride). Results show that the vital capacity and the value of respiratory function parameters, measured under forced conditions, were partly significantly lower than those given as predicted values for healthy individuals. Maximal inspiratory flows indicated the greatest decrease. After intravenously administered Tensilon, the pathologically reduced maximal inspiratory flows increased. This positive effect of Tensilon can mark the alteration of the respiratory muscles and also the undertreatment of the patients. The observation that Tensilon may increase -- with some permanency -- the respiratory flow resistance and may decrease the maximal expiratory flow values, draws attention to the side effect (causing obstruction of the bronchi) of the drug, limiting its therapeutic use for patients in myasthenic crisis, especially in those complicated by obstructive lung disease.     

Myasthenia gravis. A survey

Myasthenia gravis is a chronic disease characterized by a fluctuating weakness of voluntary muscle, with a preference for the muscles innervated by cranial nerves. The pathophysiological mechanism is a loss of postsynaptic acetylcholine receptors to less than 20–30% so that the safety margin of neuromuscular transmission is lost. It is probable that the function of the remaining acetylcholine receptors is impaired by antibodies against receptor proteïn, which can be demonstrated in the serum in 80–90% of the patients, and which are highly specific for the disease. An experimental autoimmune myasthenia can be induced in many animal species by immunization with purified receptor proteïn and this disease is remarkably similar to the human myasthenia with exception of the fluctuating course. The human disease has to be considered as an autoimmune disease, although the initiating mechanism is unknown.The occurrence of tumors of the thymus in 10–15% and the presence of germinal centres in about 70% of the thymus glands removed by operation are highly suggestive of the importance of the thymus in the pathogenesis, but the definite mechanism (harbouring of an abnormal antigen in myoid cells, or/and false instruction of thymocytes with lack of suppressor cells) is essentially unknown.In most patients the disease tends to have a favourable course from 5–10 years after onset and complete remissions occur in about 20% after 10–20 years.Therapy with anticholinesterases, providing an increase in acetylcholine, is of partial benefit in most patients. Thymectomy has an excellent effect in about 30% of the patients without thymoma under the age of 40 during the first three years of the disease, and is of benefit in still another 30–40%. The use of prednisone and immuno-suppressive drugs has improved the prognosis of the 20% of the patients with severe life threatening symptoms, half of whom have a thymoma.     

Myasthenia gravis with features of the myasthenic syndrome. An investigation with electrophysiologic methods including single-fiber electromyography.

A 47-year-old woman had myasthenia gravis with only moderate weakness and a consistently poor response to anticholinesterase medication. She was investigated with routine electrophysiologic studies and single-fiber electromyography. The studies showed a limited effect of anticholinesterase medication. There was a decrement to 2 Hz stimulation of not less than 25 percent regardless of medication and administration of edrophonium. With faster rates of stimulation (10 to 20 Hz), there was a facilitation up to 190 percent. In addition, with postcontractive or post-tetanic potentiation the action potential in the abductor digiti minimi muscle was increased from the initial value of 2.5 mv or less to up to 6 mv. Single-fiber electromyographic investigations showed increased jitter and blocking with little response to drugs, as well as facilitation in a large number of motor end-plates in association with both voluntary activity and repetitive stimulation. The findings indicated a mixture of phenomena seen in myasthenia gravis and the myasthenic syndrome.     

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.     

Myasthenia gravis and pregnancy

Treatment considerations for women who have MG and are of childbearing age are complicated. When possible, before pregnancy, establishing a plan for therapy is ideal, recognizing the potential concerns for the patient and the fetus. Decisions about treatment during pregnancy must balance the potential complications for the fetus, the patient, and even the integrity of the pregnancy. Most women who have MG are able to complete pregnancy successfully and deliver a healthy baby; however, there always is some risk that NMG may occur. Pregnant patients who have MG are served best at centers capable of providing coordinated expert care from neurologic, obstetric, and pediatric providers.     

Myasthenia gravis and pregnancy

Myasthenia gravis (MG) is an autoimmune disorder with bimodal age of presentation, occurring in young women of reproductive age and at an older age in men. Occasionally, MG is diagnosed during pregnancy. Management of MG includes symptomatic treatment with cholinesterase inhibitors and immunosuppressive therapy for controlling the disease activity. Treatment of MG in women of reproductive age, who may be contemplating pregnancy, requires discussion regarding the choice of medication as well as the understanding of risks/adverse effects involved with various treatments. During the peripartum period, it is essential to ensure careful monitoring of the disease state along with the well-being of the mother and fetus and to coordinate neonatal monitoring overseen by a multidisciplinary team comprising a high-risk maternal fetal medicine specialist, a neurologist familiar with these complex issues, and a neonatologist.     

Myasthenia gravis and pregnancy

Myasthenia gravis is an autoimmune disease characterised by fluctuating muscle weakness, which worsens during activity. It affects particularly scapular and pelvic girdles, axial and bulbar muscles. Myasthenia gravis is twice more frequent in women and symptoms often appear in the second and third decade of life. Thus, a growing number of women affected by this condition become pregnant. To minimise the effects of myasthenia gravis on pregnancy and the newborn, and to avoid myasthenia crisis in the post-partum, the pregnancy must be planned as far as possible. During pregnancy, treatment must be reviewed due to the threat of teratogenic effects (mycophenolate mofetil, rituximab), and the follow-up must be multidisciplinary.     

Myasthenia gravis. Immunological studies in a young child treated with thymectomy and immunosuppressive drugs

A case of severe myasthenia gravis diagnosed in a 12-month-old girl is described. Thymectomy at 15 months of age had only a negligible effect on the course of the disease. Treatment with cholinesterase inhibitors, prednisolone and azathioprine was started. After one year of combined treatment she was symptomfree and 3 years later treatment with cholinesterase inhibitors and prednisolone was discontinued. Attempts to withdraw azathioprine have so far been unsuccessful, leading to relapse of the disease. IgG-antibodies against cholinergic receptors were lowered to near normal, whereas the levels of total plasma immunoglobulins remained normal. The proportion of T-lymphocytes in peripheral blood was reduced during the first weeks after thymectomy, but has since been normal. Lymphocyte function measured by PHA stimulation remained normal all the time. The girl grew and developed normally without complicating infectious diseases in spite of her severe disease, thymectomy and immunosuppressive treatment.     

Myasthenia gravis in the dog

An account is given of four cases of myasthenia gravis in the dog. All animals showed fatigue, and considerably reduced tolerance to exercise. Recovery followed rest or treatment with neostigmine. Three animals, two of which are still alive, had dilatation of the oesophagus. The fourth eventually died from an aortic body tumour. The occurrence of myasthenia in the dog may be of value in elucidating the cause of the disease in man.     

Myasthenia gravis: steroid-induced effects on lymphocyte subpopulations in myasthenia gravis.

Lymphocyte subpopulations from patients with myasthenia gravis were evaluated during chronic steroid therapy. A marked lymphocytopenia (10-70%) was initially (day 3-21) noticed as well as a preferential depletion of thymus-derived cells which paralleled the clinical deterioration. Thus there was a relative increase in B cells, although their absolute number remained rather constant. These changes were reverted within 2-4 weeks in spite of continuous treatment. These findings are compatible with a release of myasthenic factors (anti-acetylcholine receptor antibodies?) during the initial steroid-induced cell damage, the long-term beneficial effects being due to loss or suppression of autoreactive helper t cells.     

Myasthenia gravis occurring in twins

Myasthenia gravis in one member each of two sets of twins is described. A 17 year old girl developed generalized myasthenia gravis at the age of 14 years, while her monozygotic twin sister has remained in good health during a three year period of observation. Another patient was a 19 year old woman with the onset of generalized myasthenia gravis at the age of 11 years, and her dizygotic twin sister has been in good health.