Cases Of Progressive Muscular Dystrophy Research Articles

Ribosuria in muscular dystrophy.

MINOT, Frank, and Dziewiatkowski 1 in 1949 reported on the discovery of pentose- and phosphorus-containing complexes in the urine of patients with progressive muscular dystrophy. They found that when 8 to 10 drops of urine from a patient with a disorder of this type was heated in a boiling water bath for 45 minutes with 5 cc. of Benedict's qualitative solution, reduction was invariably obtained. The substance responsible for this reduction was identified as d -ribose, which is excreted as a phosphorus-containing complex. Orr and Minot 2 suggested that this observation could be made the basis of a diagnostic test for muscular dystrophy. They examined specimens of urine from 26 cases of progressive muscular dystrophy of all types, from 6 of dystrophia myotonica, from 5 of myotonia congenita, and from 3 of amyotonia congenita and discovered ribose in all of them. On the other hand, a negative result was obtained

Osseous changes in myopathy.

The skeletal changes observed on radiographic examination in 38 cases of progressive muscular dystrophy (22 Duchenne type, 8 facioscapulohumeral, 8 juvenile), 17 cases of dystrophia myotonica and 6 of myotonia congenita are reported and are related to the findings of other authors. Constant findings in early cases of muscular dystrophy included narrowing of the shafts and rarefaction of the ends of long bones, impaired development of flat bones, and coxa valga. At a later stage of the disease, scoliosis, widespread decalcification with disorganisation of cancellous structure and loss of the lines of force were noted and sometimes progressed to gross distortion and disorganisation of the skeletal system. The severity of the changes depended upon the age of onset and the rate of progress of the disease. Similar appearances were noted in the wasted limbs of four patients who had suffered from poliomyelitis at an early age and in one case of dermatomyositis. It is concluded that the osseous changes in muscular dystrophy are not due to an associated genetic factor or to a “progressive osteomyopathy”. They can be entirely related to disuse, to the absence of the stresses and strains imposed upon the bones by muscular attachments in the normal individual, and to the development of abnormal postures of the body and extremeties as a result of muscular weakness and/or contractures. In the cases of dystrophia myotonica, bone changes were confined to the skull. The dimensions of the sella turcica and the thickness of the skull vault in these cases were compared statistically with those in 60 normal control subjects of comparable age and sex. The sella turcica was found to be significantly smaller and the skull vault significantly thicker in the dystrophic individuals. These changes became progressively more marked with age and increased duration of the disease. The measurements in six cases of myotonia congenita and in six unaffected relatives of myotonic individuals did not differ significantly from those in the normals on the one hand or from those in dystrophic patients on the other, but all six cases of myotonia congenita were comparatively young. Cranial hyperostoses, bridging of the sella turcica and intracranial calcification did not occur more often in the dystrophic cases than in the controls. The paranasal sinuses were large and the jaw was prognathous in two cases, but again it was not possible to say that these features were significantly more common in the patients. In confirmation of the work of other authors it can be said that reduction in size of the sella turcica and increase in thickness of the skull vault are constant features in cases of dystrophia myotonica. Cranial hyperostosis and some of the other features previously described may be due to a different gene, associated by chance in certain dystrophic families.

Inorganic phosphate response to intravenous glucose administration in progressive muscular dystrophy.

One outstanding biochemical finding in progressive muscular dystrophy (P.M.D.) is excessive creatinuria. Much of the experimental work on the disease therefore has been centered on creatinecreatinine metabolism. The conclusion has now been reached that the creatinuria in this condition arises from a normal endogenous creatine production in the presence of impaired removal of creatine from the blood stream as a result of the severe diminution of muscle mass (1). It has been furthermore inferred that such parts of the muscles which survive, remove creatine at a normal rate. This decrease in functional muscle mass appears to be a common feature in all distinct cases of progressive muscular dystrophy. In view of the well established role of carbohydrates as a source of energy in muscular activity, it is surprising that until now hardly any evidence has become available of a disturbance of carbohydrate metabolism in P.M.D. Abnormalities in glucose metabolism have been reported, including hypoglycemia, by McCrudden and Sargent (2, 3), reduced sugar tolerance by Janney, Goodhart, and Isaacson (4), and increased utilization of glucose by Magee (5), but more careful studies by Shank, Gilder, and Hoagland failed to confirm these results (6). In evaluating these negative findings of oral and intravenous glucose tolerance studies, it should be kept in mind that in the process of the removal of glucose from the blood stream in fasting subjects, the capacity of the liver is probably large enough to compensate for any deficiency on the part of the musculature. However, a crude measure of the respectiye portions removed by these tissues seems to be possible by the simultaneous recording of inorganic serum phosphate during the glucose tolerance test. Pollack and his coworkers (7) have demonstrated that phosphate is removed from a glucose and phosphate-containing perfusion fluid by the isolated hind limb, but not by the isolated liver of the dog. Recently, the estimation of a blood glucose and inorganic phosphate curve, after an oral or intravenous glucose load, has been used for diagnostic purposes in diabetes mellitus, various forms of liver dysfunction and in the study of glucose resorption in tropical sprue (Forsham and Thorn [8], Volk and Lazarus [9], and Fourman [10]). In the present report, this method has been used in the study of five cases of P.M.D., and the results have been compared to those obtained in normal subjects.

Inheritance of diseases primary in the muscles

1. 1. Hereditary muscular diseases can best be studied in large family groups in which the variety of expressions of the same gene can be identified. Extending examinations by physicians to greater numbers of individuals in kindreds being studied will also add much to our understanding of these diseases and our knowledge of the pattern of their inheritance. 2. 2. Progressive muscular dystrophy is perhaps the most important and best known group of muscular disorders. 3. 3. Most cases of progressive muscular dystrophy can be classified into two general groups, the facioscapulohumeral type and the childhood type. Each of these is inherited as a separate genetic entity following a different pattern of inheritance. 4. 4. Facioscapulohumeral progressive muscular dystrophy varies in its form of expression. Its age of onset is usually between seven and twenty years. It is inherited as an autosomal dominant. 5. 5. Childhood progressive muscular dystrophy differs from facioscapulohumeral muscular dystrophy both in its mode of inheritance and in its pattern of expression. The age of onset is usually about three years. There is good evidence that it is inherited as a sex-linked recessive trait. 6. 6. The gene producing childhood muscular dystrophy has a high mutation rate. Its minimum mutation rate is roughly estimated at one in 10,000 (approximately 1 × 10 −5). 7. 7. Three types of myotonia are discussed, myotonia congenita (Thomsen's Disease), paramyotonia and myotonia dystrophica. 8. 8. Myotonia congenita is not a common disease. It is congenital or can be identified at a very early age. It is inherited as an autosomal dominant. 9. 9. Paramyotonia is a rare disease. It is expressed as an immobility of the muscles brought on by cold. It can be detected when a child is but a few months old and is inherited as an autosomal dominant. 10. 10. Myotonia dystrophica is the most common as well as the most severe form of the myotonias. It is inherited as an autosomal dominant with a wide variability of expression. 11. 11. It is evident that all cases of family periodic paralysis described in the literature are not due to the same mutation. In the kindred studied at the University of Utah the defect was inherited as an autosomal dominant. 12. 12. Since the traits described as being due to autosomal dominant genes have not occurred in the homozygous condition it cannot be determined whether or not dominance is complete or what the expression of the homozygoteis T able II Statistical, Comparison of data on kindred with periodic paralysis with the theoretic behavior of a dominant trait ∗ Phenotypes Observed Calculated Deviation Standard Error D/SE Normal (pp) 36 34 2 4.12 485 Affected (Pp) 32 34 2 Total 68 68 ∗ From Tyler, Stephens, Gunn and Perkoff, J. Clin. Investigation, 1951.

Proceedings of the Pediatric Society of South Sweden

Brita Mannerheim: Dermatomyositis treated with cortisone. Vera Oldfelt: Oligophrenic children treated with glutamic acid. J. Löfvenberg: Two cases of progressive muscular dystrophy treated with insulin and a carbohydrate‐rich diet. G. IIerliz: Some cases of hypertension in children. G. Herlitz: Some investigations on circular caries.

The heart in progressive muscular dystrophy.

A case of progressive muscular dystrophy with cardiac involvement in a young Negro man is reported. The presenting problem was cardiomegaly and congestive heart failure. It was not until compensation was achieved that the underlying myopathy became apparent. Death was unexpected and presumably sudden. An unusual finding at the postmortem examination was the marked thickening of the endocardium. The literature in regard to the clinical and pathologic manifestations of cardiac involvement in this myopathy is reviewed.

Acetylcholine sensitivity in diseases of the motor system with special regard to myasthenia gravis

In normal subjects the threshold amount of acetylcholine which could produce a motor response by intra-arterial injection was 100–350 μg. (33 persons). In 17 out of 18 cases of myasthenia the acetylcholine sensitivity was less than normal. Treatment with prostigmine increased the acetylcholine sensitivity both in normal and myasthenic persons. Eight out of 10 cases of progressive muscular dystrophy showed a reduced acetylcholine sensitivity. In one case of myotonia (Thomsen) an extreme increase in the sensitivity to acetylcholine was found. As is the case in annual experiments, denervation in man is accompanied by an increase in acetylcholine sensitivity. In amyotrophic lateral sclerosis and traumatic lesions of peripheral nerve the sensitivity was considerably increased. The use of intra-arterially injected acetylcholine as an aid in the differential diagnosis between neurogenic and myogenic affections is discussed.

The Occurrence of Unusual Amounts of Estrogens in the Urine of Boys with Progressive Muscular Dystrophy1

IN VIEW OF RECENT reports (1, 2, 3) that large doses of vitamin E cause improvement in certain cases of progressive muscular dystrophy we have been interested in the problem of what factors might increase the demands for vitamin E or might be antagonistic to the biological action of alpha toco’ pherol. The suggestion has been made (4, 5) and later criticised (6) that the presence of excessive amounts of estrogenic substances may have such an effect. Without entering this controversy it suffices at the present time to state that these reports led us to study the excretion of estrogens in the urine of several young boys with typical pseudohypertrophic progressive muscular dystrophy. Our procedure for the extraction and bioassay of estrogens was essentially that described by Cherry and Bernstein (7). A liter or less of urine from these patients, acidified by the addition of 5 cc. of concentrated HC1 to each 100 cc. of urine, was boiled with a reflux condenser for 1 hour. After cooling the urine was vigorousl...

CREATINURIA IN ADOLESCENT MALES: II. THE EFFECTS OF THE ORAL ADMINISTRATION OF EPHEDRINE SULPHATE

Edgeworth 1 reported the first case of myasthenia gravis in which ephedrine sulphate was used with beneficial results. Since this publication, ephedrine sulphate has at times been employed in conjunction with glycine in the treatment of this disease. Studies of its effects, when used alone, on the creatine excretion in cases of myasthenia gravis have to our knowledge not been made. Reinhold and his associates 2 report a probable case of progressive muscular dystrophy in which ephedrine was used in conjunction with glycine with a resulting definite increase in the twenty-four hour creatine excretion. In this paper are reported the results obtained when ephedrine was administered orally to healthy adolescent males known to excrete creatine. These boys were all students engaged in a similar daily routine of study, exercise and diet during the period of investigation. METHOD OF INVESTIGATION The preformed and total creatinine determinations were made according to the

THE PATHOLOGIC FINDINGS IN THE HEART MUSCLE IN PROGRESSIVE MUSCULAR DYSTROPHY

While observing the clinical course of several cases of progressive muscular dystrophy, my attention was called to the manner in which patients who had remained in statu quo for fairly long periods of time, would, without warning, suddenly develop in rapid succession hypostatic pneumonia, pulmonary edema, hydropericardium and hydrothorax, culminating in death. Cardiovascular disturbance seemed best to explain these phenomena, and in two cases reported by Goodhart and myself,1lesions were found in the heart muscle, essentially of the same character as those found in the skeletal muscles. In remarkably few cases of pseudohypertrophic muscular atrophy has a study of the heart muscle been made. Oppenheim,2referring to the few cases recorded,3without giving reason for his opinion, says that he considers myopathic involvement of the heart muscle doubtful. Marinesco,3in his splendid monograph on the disease of muscles, devotes a few paragraphs to the changes

CHEMICAL CHANGES IN THE BLOOD AND URINE IN PROGRESSIVE MUSCULAR DYSTROPHY, PROGRESSIVE MUSCULAR ATROPHY AND MYASTHENIA GRAVIS

In May, 1916, we 1 reported the following findings in a case of progressive muscular dystrophy: (1) low blood sugar; (2) low cholesterin content of the blood; (3) creatinuria; (4) a rise in the sugar content of the blood accompanied by a corresponding increase, in muscular strength following treatment. We now submit further data 2 regarding the first patient, and figures for the glucose and cholesterin content of the blood and the creatin content of the urine in other cases of progressive muscular dystrophy, in progressive muscular atrophy, in myasthenia gravis, and — as controls — in conditions not accompanied by myasthenia of any form. 3 BLOOD SUGAR The blood sugar in these cases (nephritis, progressive muscular dystrophy and myasthenia gravis excepted) falls between 0.09 and 0.13 per cent.6 Since but few of these patients were in good health, the figures are not offered as normal standards; but other investigators have found approximately

HYPOGLYCEMIA AND PROGRESSIVE MUSCULAR DYSTROPHY

We recently made urine and blood examinations in a typical case of progressive muscular dystrophy which was being studied clinically by Drs. Goldthwait and Spear of Boston. The clinical findings are to be made the subject of a separate report, but the chemical findings seem well worth recording, even though they represent the data from but one case, since, if confirmed in other cases, they constitute a distinct contribution to our knowledge of carbohydrate metabolism. They are, therefore, published in the hope that similar examinations will be made by any other investigators who may observe a case of this uncommon disease. <h3>THE OBSERVATIONS</h3> The patient was a man 33 years of age who showed no abnormalities except progressive muscular weakness. He was put on a constant diet; the urine was saved and examined quantitatively for calcium, magnesium, nitrogen, creatinin, creatin, uric acid, and ammonia ; and the blood for