Treatment of Myasthenia Gravis

Abstract

Myasthenia gravis is a rare disease. Viets 1 has estimated that the total number of cases in the United States is about 1,500. In spite of this, there is widespread interest in the disease because of the challenge presented with regard to its cause and treatment, because of the complex nature of the pathologic physiology involved and because modern advances in biologic chemistry have afforded a new array of technics for its study. Consequently, there is considerable literature dealing with the condition from groups of investigators with widely differing interests and approaches. CLINICAL FEATURESThe classic clinical picture of myasthenia gravis permits its easy recognition. The undue fatigue of voluntary muscles after exercise, their return to normal or near normal after rest, the absence of muscular atrophy, the mildness of symptoms in the forenoon as compared with the afternoon and evening, the variable clinical course which may be interspersed with spontaneous remissions and relapses and the failure on neurologic examination to demonstrate evidence of structural changes either in the central nervous system or periph¬ eral nerves have enabled physicians accurately to diag¬ nose the disease long before the advent of specific measures for its detection.The muscles most frequently affected are those con¬ cerned with extraocular movements, the involvement of which results in ptosis, strabismus and diplopia in approximately 60 per cent of cases. Then in order of frequency occur generalized weakness, weakness of the extremities, dysarthria, dysphagia, difficulty in masti¬ cation, weakness of the facial muscles and weakness of the muscles of the neck. There may be many variable combinations of muscle group weakness which may show shifting from one set of muscles to another as the disease progresses. Untreated, the disease runs a fatal course in 50 to 75 per cent of cases in a fewyears, but under present methods of therapy the mor¬ tality rate is probably about 10 per cent.1 Death usually results from respiratory paralysis or bronchopneumonia of the aspiration type. DIAGNOSISTo make the diagnosis certain, several highly specific procedures are available. The most satisfactory of these is the intramuscular administration of 1.5 mg.neostigmine methylsulfate with 0.65 mg. atropine sulfate, to prevent gastrointestinal symptoms, accord¬ ing to the plan devised by Viets.2 Recently Tether :; has recommended that the diagnostic test be performed by giving 0.5 mg. of neostigmine intravenously instead of 1.5 mg. intramuscularly. He believes that the intra¬ venous method gives superior results. These tests will result in the abolition of symptoms, or in severe cases their decided amelioration, in from fifteen to thirty minutes by the intramuscular route or in five minutes by the intravenous method. In no other form of muscular asthenia does a response of comparable magnitude occur after the injection of neostigmine. In patients with difficulty in swallowing the correction of the weakness of the pharyngeal muscles by this method c...

Multiple smooth muscle hypertrophies in a newborn infant.

“…As smooth muscle hypertrophy has never been described in newborn infants of myasthenic mothers having neostigmine, particularly in high doses (Stone and Rider, 1949;Tether, 1955;Fraser and Turner, 1963), we accept that smooth muscle hypertrophy in an infant born to a myasthenic mother so treated may be a chance combination. But in view of the pharmacological actions of neostigmine we consider that a large maternal dose of neostigmine (800 mg. daily) crossing the placenta to the foetus could explain the findings in this case.…”

“Crisis” in myasthenia gravis: An historical perspective

“…Use of the singular word “crisis” as a stage of MG occurs in a 1949 review by Stone and Rider19: “In the stage of crisis intravenous neostigmine is indicated and can be given in large amounts.” Viets's 1944 record22 of 31 mg neostigmine intramuscularly daily was topped in 1951 by Rider et al,15 who gave 336 mg of intramuscular neostigmine over 24 hours! The latter authors described their patient as being in what they called “a typical myasthenic crisis—dyspnea, weakness and much mucus and saliva which she could not expectorate or swallow.” Nowadays, we would consider that their patient might actually have been suffering from too much anticholinesterase medication, a so‐called “cholinergic crisis.”…”

Neonatal Myasthenia Gravis

“…She was last seen in November, 1950, when she was again symptom-free and doing all her own housework as well as looking after her 2-year-old child; the blood pressure was 130/80. Twelve cases of myasthenia gravis occurring in newborn infants of myasthenic mothers have been reported (Strickroot et al, 1942;Wilson and Stoner, 1944;La Branche and Jefferson, 1949;Levin, 1949;Nilsby, 1949;Stone and Rider, 1949;Geddes and Kidd, 1951;Holt and Hansen, 1951 ;McKeever, 1951). In view of the rarity of the condition we think it justifiable to present a further case.…”