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Treatment of some chronic muscular diseases

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        Abstract

        Dr. Travell: The list of chronic diseases of the skeletal muscles which we have considered today includes myasthenia gravis, myotonia congenita, myotonia atrophica, familial periodic paralysis, amyotrophic lateral sclerosis, progressive muscular atrophy, progressive muscular dystrophy, the myopathies of Graves' disease, dermatomyositis and fibromyositis (fibromyalgia).
        These conditions are distinguished from each other by a variety of clinical features and their differential diagnosis is not ordinarily difficult. However myasthenic symptoms may sometimes complicate the picture of Graves' disease and raise the question of the coexistence of a primary muscular dystrophy and hyperthyroidism. The fact that iodine administration in Graves' disease reduces the spontaneous creatinuria and increases the retention of creatine often serves to differentiate the two. Neostigmine relieves the myasthenic symptoms in both conditions and does not influence creatine excretion in either. In view of the diagnostic, and at times prognostic value of the creatine tolerance test, the normal values and standard conditions for this test are discussed.
        The causes of the chronic muscular diseases listed above are unknown and their treatment is, for the most part, unsatisfactory. The drugs and measures which received special consideration are neostigmine, thymectomy, quinine, ephedrine, epinephrine, calcium, potassium chloride, cytochrome C, vitamin E with accessory factors and glycine.
        In myasthenia gravis, removal of the thymus appears to cure a small proportion of cases. Neostigmine is highly effective in relieving the muscular weakness and fatigue. It is a double-edged sword and proper dosage is a matter of the greatest importance. There was a belief that the therapeutic effect resulted from its inhibition of cholinesterase, but now there is new evidence indicating that the beneficial effect is due to direct stimulation of the muscle, and that excessive doses may increase the weakness through the anticholinesterase action which gives rise to a curare-like effect of the increased acetylcholine at the muscle.
        In familial periodic paralysis, an oral dose of 5 Gm. of potassium chloride often relieves the attack promptly, and doses of 2 to 4 Gm. daily may prevent recurrences.
        In myotonia congenita, quinine, in oral doses of from 0.3 to 0.6 Gm. several times daily, often accelerates the muscular relaxation after a movement. Epinephrine and calcium are also sometimes of value.
        There are preliminary observations indicating that daily intravenous doses of 50 mg. of cytochrome C may control the muscular disability of amyotrophic lateral sclerosis and related diseases.
        New observations suggest that in progressive muscular dystrophy and dermatomyositis certain “accessory substances” are needed for the utilization of vitamin E, as indicated by diminished urinary excretion of creatine, following their administration. Preparations which when fed together with vitamin E to patients with these disorders have been shown to have an effect on creatine excretion, include normal gastric juice, certain sugars present in pectin and wheat germ, and also gastric mucin which contains some of the polysaccharides shown to act as “accessory substances.” The clinical importance of these dietary factors has not as yet been satisfactorily demonstrated. The results open up the vista, however, that the etiology of these, and possibly of other members of this group of diseases, may be specific nutritional defects, and point the way to new lines of investigation for the solution of the vexing problems of therapy in these progressive muscular diseases.
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