DIAGNOSIS OF MUSCLE DISEASE
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As already stated, the symptoms and signs of muscle disease are most helpful when considered in connection with the age of the patient at the time of onset, their mode of evolution and course, and the presence or absence of familial occurrence Since many of these diseases are hereditary, a careful family history is important Stated differently, the familial occurrence of a muscle disease practically always indicates a genetic causation The pattern of inheritance has diagnostic signi cance, and, if genetic counseling or prenatal diagnosis is a consideration, a detailed genealogic tree becomes essential Historical data may be insuf cient; it is often necessary to examine siblings and parents of the proband The molecular genetics and other genetic aspects of the heritable muscle diseases subjects of intense interest in recent years are discussed at appropriate points in the chapters that follow As also stated earlier, of importance from a diagnostic standpoint is the principle that primary diseases of muscle seldom if ever are the cause of acute, widespread paralysis Paralytic states evolving over the period of a few days are usually due to the GuillainBarre syndrome, less frequently to other neuropathies, and now very rarely to poliomyelitis; one must also consider certain spinal cord diseases (Chaps 44 and 46) Nevertheless, there are exceptions, the most notable being disorders of neuromuscular transmission and myopathy in critically ill patients who have been exposed to high doses of corticosteroids Botulinum toxin can paralyze muscles within a few hours by blocking ACh release, and rarely myasthenia gravis or a myasthenic syndrome related to aminoglycoside antibiotic therapy may develop over days or less Also, in the rare disorder known as thyroid storm, there may be the rapid evolution of widespread muscle weakness, the defect evidently in the contractile mechanism of the muscle bers Hypokalemic paralysis, as in hyperaldosteronism, and an attack of familial periodic paralysis due to either hypo- or hyperkalemia may come on within a few hours Severe cases of toxic myopathy, especially those due to alcohol or to statin drugs can be at times quite severe and occasionally abrupt in onset Finally, a paroxysm of myoglobinuria, due to an infection or a metabolic myopathy, especially if there has been unusually strenuous exertion, may be followed within hours by a rapidly developing paresis of limb muscles, usually in association with severe pain Thus the occurrence of acute paralysis raises the consideration more of neurologic than of myologic disease In the relatively rare instances of acute generalized myopathy, diagnostic suspicions are con rmed by measurements of electrolytes, muscle enzymes (CK and aldolase), the appearance of myoglobin in the urine and by nerve conduction studies and needle electrode examination of mus-
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Nonmuscular Abnormalities in Muscular Diseases
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Clinical studies have divulged the involvement of many organs in certain diseases formerly thought to be purely myopathic Some of the nonmuscular abnormalities, such as dislocation of the hips in several of the congenital myopathies, are secondary to the inadequate action of immature muscles More important is the evidence that an abnormal gene and a depletion or other abnormality of the gene product may affect many systems to such a degree that they assume diagnostic importance For example, in congenital dystrophy of the Fukuyama type and in Duchenne and myotonic dystrophies, cerebral development may be impaired with resulting mental retardation In congenital muscular dystrophy of the Walker-Warburg and the Santavuori types, there is maldevelopment of both eye and brain The cardiac musculature or conducting system is often damaged in Duchenne dystrophy, myotonic dystrophy, Emery-Dreifuss dystrophy, Friedreich ataxia, Kearns-Sayre disease, and other mitochondrial disorders; in carnitine de ciency; and in some other adult dystrophies In addition, a myocarditis may be quite prominent in polymyositis
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