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The heart and lungs in myotonic muscular dystrophy
The Heart
and Lungs in Myotonic
Muscular
Dystrophy* PAUL J. New
CANNON,
York,
New
VOL.
32,
MAY
1962
York
abnormalities of the heart and lungs which were observed in eleven patients studied at the Columbia-Presbyterian Medical Center, The patients were not selected because of their cardiopulmonary problems but constitute a group either admitted to the medical wards or followed in the clinics because of their skeletal muscle disease during the years 1956-1960. Emphasis will be placed on the case histories of four of these, including two who came to autopsy, in whom the cardiac or pulmonary abnormality was a prominent feature of the clinical course.
muscular dystrophy (dystrophia myotonica) [ 11 is a familial disorder characterized by myotonia, a peculiar delay in the relaxation of contracted muscle, and by progressive muscular atrophy and wasting. The entity was originally separated from myotonia congenita in 1909 by Steinert [ 71 (hence the eponym, Steinert’s disease) and the classic clinical picture was described by Adie and Greenfield [Z] in 1923. The main features include apparent onset at about twenty to thirty years of age, muscular atrophy of the face, neck and forearm, myotonia confined to a few muscles (usually hand grasp alone) and progressive loss of tendon reflexes, in the face of unimpaired sensation. Various extramuscular phenomena contribute to the clinical picture, particularly cataracts, frontal alopecia, general wasting and testicular atrophy. In 1911 Griffith [3] provided a clinical description of a patient with dystrophia myotonica who had a pulse rate of 46 to 30 per minute; since that time an increasing number of reports have appeared describing cardiac abnormalities in patients with the disease [4]. Subsequently, Waring, Ravin and Walker [5] considered in detail the cardiovascular abnormalities in thirteen patients with this disorder, and commented on the tendency to hypotension, bradycardia and vasomotor phenomena. They also noted electrocardiographic abnormalities in six of eight patients in whom electrocardiograms were taken. More recent studies [6,7] have demonstrated the occurrence of cardiopulmonary insufficiency with alveolar hypoventilation. This clinical experience has led to the modern view that the abnormality of skeletal muscle in myotonic dystrophy is only one facet of a generalized disorder. It is the purpose of this paper to report the YOTONIC
* From the Department
M.D.
CLINICAL
SUMMARY
Table I summarizes the clinical, pulmonary and cardiovascular findings of the eleven patients. As can be seen, none were hypertensive. Eight of the eleven had electrocardiographic abnormalities (73 per cent; these included first degree heart block, atria1 flutter and ~brillation, abnormal intraventricular conduction, right and left bundle branch block, and abnormal T waves>. In two of the three patients with atria1 flutter or fibrillation, the ventricular rate was below 100 per minute even though the patients were receiving no medication. In two of the eleven patients (R. R. and K. D.) the onset of the cardiac arrhythmia anteceded recognition of the neurologic disease. Three patients had left-sided heart failure, three cardiomegaly. Only one patient (A. S.) had a murmur which was considered to be clinically significant; this was a grade 2 systolic murmur localized between the left sternal border and apex. There was no consistent correlation between the degree of electrocardiographic or cardiac abnormality and the severity of the skeletal muscular disease. Four patients had pneumonia. The one patient
of Medicine, Columbia University College of Physicians and Surgeons, and the Presbyterian Hospital, New York, New York. Manuscript received June 14,1961.
765
‘rresent
Present
Present
0
i
0
k5 yr. c&a&%; 14 yr. dyapnea; If yr. weaknnesn.un,
As life, baidness lwotonb; 3 yr mrlness; 2 montha drag& of right foot
zjegiitin
P&in,
Poeitive
‘resent
0
ktb; 3 yr. ptonis; 2yr.fbilblgYision
I5 yr. ptais, genorsliced weaknes% ewe&IlY of leg and amu
‘resent
Positive
oeumonia
IN
TABLE FUNCTION
H.B.,37, white female
of
weak-
:a&& nhouldor Birdlo, upper and lower extremity musculature; absent deep tendon refiexw; myotenia
WI,
atrophyof
PULMONARY
i.araIi~
AND
baitire
Symptoma and Dumtirm
OF CARDIAC
L B., 47, white, fednsle
andSex M.Q.,43, Nego, mlrle
.- ,.
INDICES
I PATIENTS
WTH
‘es
Normal heart and lungs
0
Normal heart and lungs
Normal heart and lunga
atiag blood ugat Iwel 147 mg. per rent
0
rlormal heart and lungs, Ghan complex
DYSTROPHY
Diabetes
MUSCULAR
0
0
WYOTONIC
-
__
. .
sinw rhythm; left axis deviation; P-R 0.18 second; QRa 0.08 second. withinnamal limits I\Tormsl
fibrillation; no axis deviation; premature WIItrioalar oontractiom from 2 foci; QI@ 0.12 meond, dot Ti.n, sin., WP. dipbasic Ta, inverted T h vs.._,; d~ycdin~n~~d Vu b1omwl sinus rhythm with no axis deltiatioq P-R 0.18 wcoad, QBa 0.w necond, S ia Vu, T inverted a%, low VW; abaormrl record with probsble termiwl intmventxicular Maduction defect ELinus bmdycsrdia; P-R 0.12 second, gas a.03 scoon&, no axis deviation: within normal sits Eiormalainoe rhythm with &St degree heart b&k; P-R 0.22 second; left nxic devi&an; left bundle branob block QRS O.l2 second I rtormai sinus rhythm; right axis deviation; P-R O.XJ second, QRS 0.09 second: within normal limits
AWi
Electrocrrk~
1
Myotonic Muscular Dystrophy-Cmwon
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-
-
-7
-
-
-
-
-I I
P
-7
‘a
cl
-L
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-
VOL.
32,
MAY
Myotonic
Muscular
(C. G.) with alveolar hypoventilation will be considered subsequently. The following four case histories illustrate certain cardiac and pulmonary complications of dystrophia myotonica: PATIENT K. r). (No. 733-08-07). A twenty-seven year old single Negro female domestic was admitted to Columbia-Presbyterian Medical Center for the first time on February 25, 1959, with .the chief complaint of palpitations and shortness of breath of one month’s duration. No member of the patient’s family suffered from neurologic disease. The past history was completely within normal limits except for a positive reaction to a Wassermann test ten years prior to admission. Because of this, the patient had been treated for ten days with parenteral penicillin. The patient was in good health until one year prior to admission when she noted the gradual onset of exertional dyspnea. One month prior to admission the dyspnea increased and she noted palpitations. The patient was a well nourished, well developed woman in no distress. The temperature was 98%., pulse 72 per minute and irregular, blood pressure 104/68 mm. Hg, respirations 16 per minute. The fundi were normal, the neck veins were flat. The thyroid gland was not enlarged; a firm nodule was felt in the left parotid gland. The lungs were clear to percussion and auscultation, and the heart was not enlarged. The second aortic sound was equal to the second pulmonic sound, the first mitral sound fluctuated in intensity, and a soft localized systolic murmur was heard at the apex. There was no diastolic murmur. Abdominal examination was within normal limits except for the finding of an enlarged uterus consistent with a pregnancy of three months. The erythrocyte sedimentation rate was 11 mm. in one hour; complete blood count and urinalysis were normal. A reaction to a blood serologic test for syphilis was positive while that of the cerebrospinal fluid was negative. The antistreptolysin titer was 12 units. The serum protein-bound iodine was 5.9 pg. per 100 ml. X-ray examination of the chest showed the heart and lungs to be within normal limits. Electrocardiography revealed atrial flutter with varying atrioventricular response; the atria1 rate was 300 per minute, the ventricular rate about 85 per minute. The QRS was 0.08 second and there was no axis deviation. The patient was given digitalis and maintained on digitoxin, 0.2 mg. given orally daily. Because of persistence of the arrhythmia, an attempt was made to restore normal sinus rhythm by quinidine, given orally. A total dose of 1 gm. during the first day of the trial produced no alteration in rhythm. On the second day the patient received divided doses of quinidine totaling 0.8 gm. following which the electrocardiogram revealed atria1 flutter with 2: 1 atrioventricular block, the atrial rate was 200 per minute and the ventricular rate was 100 per minute.
~ys~ophy-cu~~~~ Shortly thereafter the patient had a Stokes-Adams attack and became pulseless. She responded to vigorous pounding on the chest and the electrocardiogram again revealed atria1 flutter with 2: 1 block. This rhythm was followed by a slow nodal or His bundle rhythm with absent P waves. Four hours later the patient had ventricular fibrillation and again became unresponsive. Emergency thoractomy, cardiac massage and direct external defibrillation were successful in restoring normal sinus rhythm. Her subsequent course was uneventful. After recovery the electrocardiogram revealed a normal sinus rhythm with a rate of 81 per minute, with incomplete A-V block (prolonged P-R interval of 0.24 second). The cause of the arrythmia remained unknown. The patient was readmitted on June 2, 1959, to the obstetrical service after an episode of syncope. In the interim she had received 9.G million units of penicillin as antisyphilitic treatment. Electrocardiogram revealed sinus arrhythmia with sinus bradycardia (rate varying between 40 and 80 per minute). Incomplete A-V block appeared during the episodes of bradycardia, at which time the P-R interval increased from 0.20 to 0.24 second; minor ST-T wave changes were noted. It was then established that during the preceding year the patient had noticed difficulty in opening a clenched fist’and difficulty in seeing out of her right eye. Myopathic facies was noted, with atrophy of temporalis, masseter and orbicularis oculi muscles. The patient had a cataract in the right eye, weakness of neck flexors, mild weakness of the proxima1 muscles of both upper extremities and the shoulder girdles, and myotonia of the muscles of both hands. Reflexes were equal bilaterally, plantar responses were flexor, and sensation was intact. Electromyo~aphy confirmed the presence of myotonia. In September 1959 she was uneventfuily delivered of a normal child. She was seen again in November 1959 for resection of an asymptomatic left parotid mixed tumor. The electrocardiogram then revealed sinus bradycardia with a rate of 55 per minute and a P-R interval of 0.20 second and QRS of 0.08 second. Comment: This patient illustrates the point that a cardiac arrhythmia or other cardiac symptoms may antedate recognized disorder of skeletal muscle as manifestations of dystrophia myotonica. During the patient’s hospitalization two Stokes-Adams attacks occurred during an attempt at conversion to normal sinus rhythm from atria1 flutter with digitalis and quinidine therapy. PATSENT R. R. (No. 742-85-87). This sixty year old semiretired executive was admitted in July 1959 with the chief complaints of inability to walk of four days’ duration, and shortness of breath of four hours’ duration. The patient’s grandfather had had cataracts ABIERlCAN
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~yotonic
Muscular dystrophy ----Canner
his father was bald; one cousin had “muscular difficulty” and his son had documented dystrophia myotonica. There was no family history of diabetes. The patient had been in good health until 1942 at which time he was hospitalized for “‘tachycardia with an irregular pulse.” At that time there was no basis for a diagnosis of hypertensive, arteriosclerotic, rheumatic or thyrotoxic heart disease. His irregular pulse persisted. In 1946, after an episode of infiuenza, he became aware of generalized weakness, and his own physician observed sluggish relaxation of his grip. A diagnosis of dystrophia myotonica was made. Subsequently, the patient noted a gradual increase in weakness. In June 1959 he was admitted to ColumbiaPresbyterian Medical Center for the first time for insertion of a suprapubic tube for relief of chronic prostatic obstruction. While in the hospital, glycosuria and a diabetic glucose tolerance curve were revealed atria1 recorded. An electrocardiogram flutter with varying degrees of A-V block, left axis deviation and right bundle branch block. The patient did well until four days prior to admission when he noted dizziness, difficulty in moving his left leg, and a low grade fever; four hours prior to admission he became extremely dyspneic. On examination the patient was an acutely ill, moderately obese man. The temperature was 101.8O~., blood pressure 84/68 mm. Hg; pulse 96 per minute and irregular, respirations 26 per minute. There was slight cyanosis of the lips and nail beds. Frontal baldness was prominent. No cataracts were noted. Examination of the fundi revealed tortuous arterioles with no other evidence of retinopathy. The neck veins were flat, the thyroid was not enlarged. There was poor thoracie expansion with diminished fremitus, dullness over the lower third of the right posterior lung where thick inspiratory rales were heard. Coarse rhonchi were evident throughout. The patient’s heart was not enlarged and the heart sounds were distant. The abdomen was normal. A suprapubic catheter was in place. Neurologic examination showed myopathic facies, generalized weakness with poor tone and atrophy of the muscles of the extremities. There was left facial weakness, a left flaccid hemiparesis, a positive Babinski sign on the left and absent deep tendon reflexes. Sensation was intact. Myotonia was present in both hands. The erythrocyte sedimentation rate was 82 mm. in one hour. The hemogram on admission was as follows: hemoglobin 16.3 gm. per cent, white blood cell count 5,100 per cu. mm., polymorphonuclear cells 87 per cent, lymphocytes 12 per cent. The blood urea nitrogen was 28 mg. per cent; a reaction to a Wassermann test was negative. The venous blood CO% content was 25 mEq. per L., and a two hour postprandial blood sugar was 171 mg. per cent. Urinalysis revealed 2-plus albumin; many white blood cells were present in the urinary sediment. A roentgenogram of the chest showed pneumonia of the VOL.
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769
lower lobe of the right lung and suggested slight left ventricular enlargement. Electrocardiogram showed atria1 flutter with varying A-V response, left axis deviation, right bundle branch block. The QRS interval measured 0.16 second and the ST-T wave changes were considered to be consistent with myocardial disease. Despite massive antibiotic therapy the patient pursued a downhill course. The major difficulty was his inability to raise his bronchial secretions. Repeated tracheal aspirations produced large amounts of purulent material. He died one week following admission. At postmortem examination (Autopsy No. 19,700) the changes in skeletal muscle were characteristic of dystrophia myotonica. Examination of the brain revealed recent encephalomalacia in the basilar portion of the pons and in the anterior commissure. There was moderate arteriosclerosis, but no occlusion of the vessels to the involved areas or of the right internal carotid was found. The upper right lung showed early acute bronchopneumonia. The lower lung field revealed bronchopneumonia with abscess formation, organization and several areas of granulomatous response with giant cells. The pericardial cavity contained 10 cc. of straw-colored fluid; the surfaces were clear and glistening without abnormality. The heart weighed 360 gm., all chambers were moderately dilated. The epicardium was normal in appearance as were the valves and the valve orifices. On gross inspection the myocardium appeared to be normal. The thickness of the left ventricular was 1.2 cm., that of the right ventricle 0.2 cm. The root of the aorta was dilated, and the intima showed mild arteriosclerotic change. The coronary arteries were patent throughout and there was no gross evidence of myocardial abnormality. Microscopic examination (Fig. 1) revealed minimally atherosclerotic coronary vessels. The myocardium of the left and right ventricles was histologically normal save for scattered small areas of focal subendocardial fibrosis. Section of the A-V node area failed to demonstrate an anatomic lesion. The Purkinje tissue was normal. Comment: The patient had a cardiac arrhythmia approximately four years prior to the onset of weakness and the diagnosis of dystrophia myotonica. Thus, cardiac symptoms and signs preceded evidence of muscular disease. During this hospitalization, left ventricular prominence was noted on roentgenogram, and atria1 flutter with varying A-V response, right bundle branch block and non-specific changes of myocardial disease were found on electrocardiography. Inability to raise bronchial secretions, presumably as a result of weakness of the thoracic musculature, complicated management of his
770
Myotonic Muscular Dystrophy-Cannon
FIG. 1. Patient R. R. Microscopic section erate atherosclerosis of a coronary vessel.
terminal. pneumonia. Examination of the heart at autapsy failed to provide an anatomic basis for the electrocardiographic abnormalities. PATIENT C. G. (No. 92-20-85). A sixty-four year old Cuban-born’ man was admitted to ColumbiaPresbyterian Medical Center for the fourth time in February 1960 for regulation of his diabetes. The patient’s brother, son and two nephews were said to have dystrophia myotonica. In 1937 the patient was seen at another hospital because of weakness and poor general coordination. A diagnosis of dystrophia myotonica was made, and the patient was treated for a short while with quinine, which was discontinued because of its failure to augment his muscular strength. A progressive disturbance of gait, speech and swallowing ensued during the subsequent years. In 1957 the patient was admitted to Columbia-Presbyterian Medical Center for the first time because of generalized weakness. The venous blood COa content was 33 mEq. per L. The hemoglobin was 16.3 gm. per cent. The fasting blood sugar was 103 mg. per cent. The chest roentgenogram was within normal limits. In 1957, because of complaints of dyspnea and orthopnea with the finding of cardiomegaly, the patient was given digitalis. In 1958 he was admitted because of pneumonia; at this time his two hour postprandial sugar level was 200 mg. per cent. Because of increasing glycosuria the patient was readmitted for diabetic regulation in February 1960. On physical examination the patient appeared chronically ill. Baldness was noted. The temperature was 98%., pulse 80 per minute, blood pressure 120/60 mm. Hg; respirations 18 per minute. The extraocular movements were normal. Fine dust-like
of the left ventricle
revealing
mod-
particles were noted in the posterior one-third of each lens. The fundi were normal. The thyroid was not enlarged and the neck veins were flat. Thoracic expansion was poor, breath sounds were distant, and no rales were heard. The left border of cardiac dullness was 1 cm. to the left of the mid-clavicular line in the sixth intercostal interspace. The second aortic sound was equal to the second pulmonic sound. There was a localized, grade 1 apical systolic murmur. Abdominal examination was within normal limits. There was marked atrophy of the facial muscles, of the sternocleidomastoids, and of the musculature of the extremities. Cyanosis of lips and of the nail beds was evident. There was no clubbing of the fingers. Deep tendon reflexes were equal and the plantar responses were flexor. Hair distribution was normal. The testicles were small. The erythrocyte sedimentation rate was 5 mm. in one hour. The hemogram was as follows: hemoglobin 18.6 gm. per cent, hematocrit 57 per cent, white blood cell count 7,900 per cu. mm. with a normal differential. &inalysis revealed a Specific gravity of 1.014, with l-plus glucose. The blood urea nitrogen was 16 mg. per cent, and the two hour postprandial blood sugar level was 243 mg. per cent. A chest roentgenogram revealed clear lung fields except for a minute area of fleck-like atelectasis at the right base, and moderate cardiomegaly with a cardiac contour suggestive of left ventricular enlargement. Electrocardiogram showed sinus rhythm at a rate of 75 per minute with incomplete A-V block (prolonged P-R of 0.24 second) and rare premature ventricular contractions, left axis deviation, intraventricular conduction defect with a QRS of 0.14 second. Arterial blood studies revealed an oxygen saturation of 78 per Cent, pH 7.39, hematocrit 48.3 per cent, Cop content 70 AMZRICAN
JOURNAL
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MEDICINE
Myotonic
Muscular
volumes per cent, CO2 tension of 62 mm. Hg. The patient’s diabetes was controlled with Orinase.@ He signed out of the hospital before pulmonary studies could be completed.
Comment: This rence
dystrophy. lips
and
fingers, breath
polycythemia, an
diagnosis
was based
diminished arterial
pCOz
cardiomegaly, interval,
poor
clear
oxygen
of left-sided and
ventricular
also
hypo-
of cyanosis expansion, lung
fields,
unsaturation Hg. heart
the
occur-
myotonic
alveolar
thoracic
of 62 mm.
intraventricular
premature
of
the in
on the findings sounds,
arterial
was his history
illustrates
hypoventilation
The
ventilation of
patient
of alveolar
failure
increased
conduction contractions
and
Of note also
defect found
and
P-R and on
electrocardiography. PATIENT M. G. (No. Z-93-08). This forty-three year old Negro mechanic was admitted to the Columbia-Presbyterian Medical Center for the first time in 1955 following a clinic study of epigastric pain. The patient was well until 1945, at which time he noticed weakness of the right leg and of the hands, which progressed during the ensuing years making it difficult for him to obtain jobs. In 1952 a lymphoepithelioma of the pharynx was treated successfully with 20,900 roentgens in air. In 1956 he was seen in the clinic with a history of two years of postprandial mid-epigastric pain (relieved by taking alkali) and a 30 pound weight loss. No history of hypertension, angina, rheumatic fever, diphtheria, myocarditis or other cardiac difficulty was elicited. Ear, nose and throat examination was within normal limits. A chest roentgenogram showed generalized cardiomegaly. Electrocardiography revealed atria1 fibrillation with multifocal ventricular premature contractions, a ventricular rate of approximately 60 per minute, a QRS complex of 0.12 second and a Q-T interval of 0.43 second. Low T waves were present in leads I, aVL and V+ Gastrointestinal series revealed a “neurogenic disturbance of swallowing” and an ulcer of the lesser curvature of the stomach. The patient was admitted to the hospital. On physical examination the patient was an emaciated, chronically ill man with dysarthric speech. The vital signs were temperature, normal; blood pressure 100/60 mm. Hg; pulse 62; respiraticns, normal. The patient had bilateral cataracts, normal fundi and was without distended neck veins or thyromegaly. The lungs were clear. The left border of cardiac dullness was halfway between the mid-clavicular and anterior axillary lines. The second aortic sound was greater than the second pulmonic sound, and there were no murmurs. Abdominal examination was within normal limits. There was testicular atrophy. There was atrophy of the facial muscles, of the
VOL.
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771
shoulder girdle muscles and of the musculature of the upper and lower extremities. The patient had generalized muscular weakness, inability to relax his grip, and diminished to absent deep tendon reflexes. The sensory examination was within normal limits. The erythrocyte sedimentation rate was 55 mm. in one hour. The hemoglobin was 9.5 gm. per cent; urinalysis was normal. The blood urea nitrogen was 28 mg. per cent. A two hour postprandial blood sugar was 83 mg. per cent. The basal metabolic rate was -39 per cent. Radioactive iodine uptake was 22 per cent at twenty-four hours. The serum cholesterol was 173 mg. per cent. A prostigmine test result was negative. It was concluded that the patient had dystrophia myotonica, gastric ulcer and cardiac disease of uncertain etiology. He responded symptomatically to an ulcer regimen and there was radiologic evidence of ulcer healing. After three months, however, roentgenograms suggested the development of a new gastric ulcer on the lesser curvature. In January 1957 the patient had shortness of breath, marked orthopnea, cough and hemoptysis. On admission he was found to be acutely ill with a temperature of 103’F., an apical pulse of 150 per minute, blood pressure 11 O/60 mm. Hg, and respirations of 30 per minute. Roentgenograms revealed a moderately enlarged heart with a prominent pulmonary artery segment. The lungs were congested bilaterally and a density noted in the lower right lung field suggested bronchopneumonia; in this area clinically coarse inspiratory rales were heard. Staphylococcus aureus was cultured from the patient’s sputum. The white blood cell count rose to 22,000 per cu. mm. He was treated with antibiotics and digitalis. Electrocardiography at this time showed atria1 fibrillation with a ventricular rate of 80 per minute, no axis deviation, and frequent premature ventricular contractions from two foci. Since the previous tracing, T waves in leads II, aVF and V4 had become flat, and inverted in leads Vs and Vs. After a period of initial improvement, on the fifth hospital day he passed a guaiac positive stool. Although it was suspected that he was bleeding from a gastric ulcer, it was decided to treat him supportively because of his poor general condition. Despite transfusions he continued to have episodes of hypotension, vomiting, coughing and hemoptysis. On January 17, 1957, the patient died. Postmortem examination (Autopsy No. 18,663) revealed skeletal muscle characteristic of dystrophia myotonica, associated with cataracts, testicular atrophy and frontal alopecia. Focal atrophy and gliosis were present in the right superior gyrus and right hippocampus. There were gastric ulcers with secondary massive gastrointestinal hemorrhage. Examination of the lungs revealed “generalized congestion and moderate edema fluid, and there was organizing and resolving pneumonia which in some areas had elicited a slight giant cell foreign body response.” The pericardial cavity contained about
772
Myotonic Muscular ~ystrophy-c~~~o~
Fro. 2. Patient M. G. Microscopic section of the left ventricular myocardium of patient. A distinct cardiomyopathy analogous to the degeneration of skeletal muscle which occurs in myotonic muscular dystrophy is apparent. 50 cc. of pale yellow fluid and the surfaces were
smooth and glistening. The heart weighed 600 gm.,
the epicardium was smooth and the usual amount of epicardial fat was present. All the cardiac chambers appeared to be somewhat dilated. The endocardium was smooth and glistening. The valves were delicate and the valve dimensions were normal. The myocardium of the right and left ventricles appeared to be somewhat thickened; left ventricle 2.5 cm., right ventricle 0.4 cm., but the myocardium of the atria appeared thin and of a firm consistency. The coronary vessels arose and were distributed normally; the vessels were widely patent throughout and were entirely free of atheromatous clot or intimal thickening. Microscopic examination of the heart (Fig. 2) revealed prominent interstitial edema with a slight increase in the interstitial connective tissue. There were small areas of focal interstitial fibrosis and about these areas the myocardial fibers appeared atrophic and/or necrotic. There were also occasional minute areas in which the myocardial fibers seemed to have dropped out. In these there was a loose meshwork of fibroblasts and lymphocytes and the surrounding myocardial fibers appeared somewhat atrophic. There was marked variation in fiber size and a great majority of the surrounding fibers exhibited hyper-
trophy. The myocardial nuclei also varied considerabIy in size, and were frequently large and pyknotic. Comment: This forty-three year old patient with moderately advanced dystrophia myotonica had evidence of extensive cardiac abnormality when first seen, i.e., atria1 fibrillation,
intraventricular conduction defect, muftiple ventricular premature contractions, cardiomegaly and, terminally, left-sided congestive heart failure. Striking histologic changes of the myocardium were present. COMMENTS
Significant abnormalities of the heart and lungs are apparent in this series of eleven patients with dystrophia myotonica. The pulmonary complications of the disease consisted of repeated episodes of pneumonia and, in one instance, of alveolar hypoventilation; the cardiac complications included electrocardiographic abnormalities, arrhythmias, Stokes-Adams attacks and left-sided heart failure. A distinct cardiomyopathy was demonstrated in one patient at autopsy. Pulmonary Complicatioas. In two of the four patients with pneumonia, the pneumonitis occurred during the terminal illness. Muscular weakness with a resultant diminished cough reflex and retention of bronchial secretions undoubtedly contributed to the poor response to antibiotic administration. No characteristic pulmonary abnormality has been noted in myotonic dystrophy at postmortem examination. Other than pneumonia in both, and congestion in one, the lungs of two autopsied patients herein described were non-contributory. Alveolar hypoventilation was present in one AMERICAN
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Myotonic Muscular Dys~ophy-Gu~~~~ patient (C. G.). This may be the result of insufficient ventilatory drive at one of four sites [8]. The defect may occur in: (1) The stimulus to respiration; (2) the respiratory center; (3) neuromuscular coordination or; (4) in the action of the chest bellows. In recent years clinical studies of patients with the syndrome of alveolar hypoventilation caused by defects at each of these various sites have been reported [o-74]. In myotonic dystrophy the defect appears to lie in the action of the chest bellows. Bashour et al. [I4 reported the case of a fifty-seven year old man with myotonic dystrophy who presented with polycythemia and cyanosis; he was found to have pulmonary function abnormalities suggestive of inadequate alveolar ventilation. Kilburn et al. [S] described a thirty-one year old man with dystrophia myotonica and mild obesity who showed marked somnolence, cyanosis and CheyneStokes breathing. Studies of this patient revealed a diminished vital capacity and a small expiratory reserve capacity and total lung capacity. The maximum breathing capacity was reduced to less than half of the predicted value. Arterial oxygen saturation ranged between 80 and 89 per cent and rose to 96 per cent after inhalation of 100 per cent oxygen for five minutes. The arterial pC0~ ranged from 56 to 60 mm. Hg, and the pH from 7.30 to 7.35. These findings were considered to be consistent with alveolar hypoventilation. Additional investigation by these workers [7] in nine other patients with dystrophia myotonica yielded similar results: reduction in total lung capacity, vital capacity and maximum breathing capacity, reduced minute ventilation, retention of CO2 and systemic arterial hypoxemia. These changes were attributed to the limited expansion of the chest bellows arising from weakness of the thoracic muscles and of the diaphragm [%?I. Myotonia of these structures, by increasing the work of breathing, could also contribute to the production of alveolar hypoventilation. One patient [77] has been described who, on fluoroscoPy> showed diminished excursions and irregular jerking movements of the diaphragm on ascent and descent, which raised the question of myotonia of the diaphragm; this patient also exhibited myotonia of the intercostal muscles on electromyography. In common with all other types of hypercapnea, the ventilatory response to carbon VOL.
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773
dioxide inhalation in patients with myotonic dystrophy and the hypoventilation syndrome was demonstrated to be subnormal 173. In contrast with another group of patients with progressive muscular dystrophy, Kilburn et al. [7] noted that the breathing of 100 per cent oxygen was accompanied by a fall in resting minute ventilation in patients with dystrophia myotonica, despite only mild hypercapnea. This observation led these authors to postulate a respiratory center depression in the disease, in addition to the obvious thoracic wall dysfunction. However, such a thesis is difficult to validate in the presence of abnormal chest mechanics [ 73,741. Cardiac ~O~~liG~~~o~s. Eight of the eleven patients described had abnormal electrocardiograms. Several observers since Griffith [3] have commented on the incidence of arrhythmias and electrocardiographic abnormalities in dystrophia myotonia. Evans [78] in 1944 noted prolonged P-R intervals in ten of thirteen patients, Spillane [19] in 1951 described sixteen patients in whom electr~ardio~aphic studies revealed low voltage T waves in eight patients, a P-R interval longer than 0.20 second in six, and slurring of the QRS complex in four. In reviewing the literature on this subject in 1951, Fisch [ZO] summarized the electrocardiographic findings in eighty-five described patients, and in 68 per cent of these, significant abnormalities were found. In 91 per cent of this group the alteration consisted of a conduction defect or a disturbance of rhythm, or both. Forty-eight per cent of the patients showed an alteration of the P-R interval, 12 per cent a prolonged QRS complex. Atria1 flutter or fibrillation was present in 2 per cent. Other abnormalities occurred but these were less frequent. Moreover, the frequency of electrocardiographic abnormalities did not vary significantly among the various age groups from twenty to over fifty years of age. The high incidence of electrocardiographic changes, and the absence of age-dependence, led Fisch to suspect that these changes were a part of myotonic dystrophy rather than a coincidental finding. One patient (K. D.), when first hospitalized had two apparent Stokes-Adams attacks; the second was secondary to ventricular fibrillation. The role of quinidine therapy in causing her attacks is speculative. In favor of the view that the drug was toxic to an abnormal myocardium
774
Myotonic Muscular Dystrophy-Camon
is the report of one patient with myotonic dystrophy and intermittent atria1 fibrillation who was given quinidine in an attempt to restore normal sinus rhythm [S]. Administration of the drug was associated with hypotension on one occasion and with paroxysmal ventricular tachycardia on another. Stokes-Adams attacks occur in untreated dystrophia myotonica. Brain [27] states that complete heart block has been seen in the disease. One of Evans’ [78] thirteen patients had two probable Stokes-Adams attacks with an interval electrocardiogram revealing a P-R interval of 0.30 second and an atypical bundle branch block. Litchfield [Z?] describes a fortytwo year old woman with dystrophia myotonica who presented with seven years of Stokes-Adams attacks causing unconsciousness, and no other cardiac symptoms. Electrocardiography showed varying degrees of A-V conduction from sinus bradycardia to complete A-V block. The ventricular complex, always abnormal, varied from right bundle branch block to left bundle branch block indiscriminately; an electrocardiogram taken during one attack while the patient was in the hospital showed probable ventricular tachycardia which, on recovery, was followed by complete A-V block. Other cardiovascular abnormalities are Iess common but can be clinically significant. In the present series these included cardiomegaly and left-sided heart failure. Similar reports have been published by others. “Sudden and unexpected death from heart failure” in a patient with myotonic dystrophy prompted Spillane’s [79] report. Cantwell [23] reported a thirty-six year old woman who first presented with left ventricular failure and pneumonia. The association of left-sided congestive heart failure, electrocardiographic conduction defect together with cataracts raised the clinical suspicion which led to neurologic evaluation and the eventual diagnosis of dystrophia myotonica. Evans [ 781 in 1944 had suggested that cardiovascular findings contribute to the earlier and easier diagnosis of this disease. The cardiac changes found at postmortem in one patient (M. G.) were distinctive and provided ample explanation for this heart failure. They resembled the characteristic changes in skeletal muscle in myotonic dystrophy [Za], i.e., enlargement of scattered muscle fibers with centrally placed muscle nuclei, isolated fibers with nuclear proliferation, and staining of
cytoplasm. In the late stages atrophy is prominent, with rows and clusters of dark-staining nuclear remnants lying in connective tissue and between fat cells. Few pathologic studies on heart muscle in this disease have appeared in the literature. Keschner and Davison [ZZj in 1933 noted in one patient that the myocardium was better preserved than the striated musculature: “the muscle fibers of the right ventricle were replaced by fat”. . . (there was) “destruction of single muscle fibers with fatty replacement, increase in sarcolemma nuclei and loss of striation.” The heart is mentioned briefly in five autopsied cases by Black and Ravin [.%I. All were within normal limits on gross examination. One heart showed “moderate variability in size of fibers with variation in nuclear size and shape.” Only left ventricular dilatation was noted in a patient of Spillane [ 191 who died from sudden ventricular failure. Fisch and Evans [27] in 1954 related in some detail the pathologic findings in a forty-one year old man with myotonic muscular dystrophy who had no cardiac symptoms or cardiomegaly but did have atria1 flutter and varying A-V block. The patient died suddenly. At postmortem the lungs were severely congested and edematous; the heart was soft and flabby, and weighed 340 gm. The coronary vessels were normal as were the valves and valve leaflets. The walls of the left and right ventricles were 1.2 and 0.4 cm. thick, respectively, with a few small hemorrhagic and mottled gray areas scattered throughout the myocardium. On microscopic examination the left atrium showed a moderate amount of fatty infiltration; sections of the myocardium revealed “diffuse fibrosis with separation of muscle fibers by fairly dense fibrous connective tissue. Hypertrophied muscle fibers with large rectangular nuclei were scattered throughout.” In one patient (R. R.) the heart was found to be normal (including the A-V node) except for moderate coronary arteriosclerosis and small areas of subendocardial fibrosis which might be expected in a patient of this age. Another patient (M. G.) had normal coronary arteries and valves. histologically, the myocardium showed changes which resembled an earlier stage of the lesion described by Fisch and Evans. Undoubtedly, such changes are unusual. However, they may represent anatomically a more severe degree of deranged myocardial metabolism than was present in the described patients with AMERICAN
JOURNAL
OF
MEDICINE
Myotonic
Muscular
myotonic dystrophy who had lesser cardiac abnormalities (arrhythmias and/or conduction defects) and no histologic changes in the myocardium. The possibility exists that the disturbances of cardiac function and cardiac anatomy noted in patients with dystrophia myotonica are, along with cataracts, baldness, and testicular atrophy, genetically determined manifestations of an inherited disorder which most obviously affects skeletal muscle. SUMMARY
Cardiac and pulmonary manifestations are reported in a group of eleven patients with myotonic muscular dystrophy. The detailed case histories of four patients in whom abnormality of the heart or lungs was prominent are presented. The pulmonary complications, frequent pneumonias and development of the syndrome of alveolar hypoventilation, are discussed. The cardiac complications, abnormal electrocardiograms, arrhythmias, Stokes-Adams attacks and left ventricular failure, are enumerated and the pertinent literature is reviewed. The postmortem findings in two of the patients are presented. In one there was a distinct cardiomyopathy analogous to the degeneration of skeletal muscle which occurs in the disease. It is suggested that the cardiopathy seen in dystrophia myotonica represents, along with atrophy of skeletal muscle, baldness, cataracts, another genetically determined manifestation of this hereditary disorder. REFERENCES
1. STEINERT, H. Uber das klinische und anatomische Bild des Muskelschwundes der Myotoniker. Deutsche Ztschr. Nervenh., 37: 38, 1909. 2. ADIE, W. J. and GREENFIELD,J. G. Dystrophia myotonica. Brain, 46: 73, 1923. 3. GRIFFITH, T. W. On myotonica. Quart. J. Med., 5: 229, 1911. 4. GUILLAIN, G. and ROUGUES, L. Le coeur dans la myotonie atrophique. Ann. mid., 31: 158, 1932. 5. WARING, J., RAVIN, A. and WALKER, C. Studies in dystrophia myotonica. II. Clinical features. Arch. Znt. Med., 65: 763, 1940. 6. KILBURN, K. H., EACAN, J. T. and HEYMAN, A. Cardiopulmonary insufficiency associated with myotonic dystrophy. Am. J. Med., 26: 929, 1959.
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7. KILBURN, K. H., EAGAN, J. T. and SIEKER, II. Cardiopulmonary insufficiency in myotonic and progressive muscular dystrophy. New England J. Med., 261: 1089,1959. 8. FISHMAN, A. P., TURINO, G. M. and BERGOFSKY, E. H. Editorial: The syndrome of alveolar hypoventilation. Am. J. Med., 23: 333, 1957. E. J., TURINO, G. M. and FISHMAN,A. P. 9. BERGOFSKY, Cardiorespiratory failure in kyphoscoliosis. il4edicine, 38: 263, 1959. 10. LUK,Q, D. S. and PLUM,F. Pulmonary function in patients convalescing from acute poliomyelitis with resoiratorv naralvsis. Am. J. Med., 12: 388, 1952. 11. CARROLL, D: ‘A peculiar type of c&diopulmonary failure associated with obesity. Am. J. Med., 21: 819, 1956. 12. BURWELL, C. S., ROBIN, E. D., WHALEY, R. D. and BICKELMANN,A. F. Extreme obesity associated with alveolar hypoventilation: A Pickwickian syndrome. Am. j: Med., 21: 811, 1956. 13. RICHTER. T.. WEST. J. R. and FISHMAN.A. P. The syndrome of alveolar hypoventilation and diminished sensitivity of the respiratory center. New England J. Med., 256: 1165, 1957. 14. RODMAN,T. and CLOSE,P. The primary hypoventilation syndrome. Am. J. Med., 26: 808, 1959. 15. BASHOUR, F., WINCHELL, P. and REDDINGTON,J. Myotonia atrophica and cyanosis. New England J. Med., 252: 768, 1955. 16. CAUGHEY,J. E. and GRAY, W. G. Unilateral elevation of diaphragm in dystrophia myotonica. Thorax, 9: 67, 1954. 17. BENAIM, S. and WORSTER-DROUGHT, C. Myotonic dystrophy with myotonia of the diaphragm causing pulmonary hypoventilation with anoxaemia and secondary polycythemia. M. Zllus., 8: 221, 1956. 18. EVANS, W. The heart in myotonia atrophica. Brit. Heart J., 6: 41, 1944. 19. SPILLANE, J. D. The heart in myotonia atrophica. Brit. Heart J., 13: 343, 1951. 20. FISCH, C. The heart in dystrophia myotonica. Am. Heart J., 41: 525, 1951. 21. BRAIN, R. Diseases of the Nervous System, 5th ed., p. 843. London, 1956, Oxford University Press. 22. LITCHFIELD, J. A. A-V dissociation in dystrophia myotonica. Brit. Heart J., 15: 357, 1953. 23. CANTMTELL,D. and HICKEY, K. Dystrophia myotonica with cardiac symptoms. Irish J. M. SC., 6: 360, 1954. 24. ADAMS, R. D., DENNY-BROWN, D. and PEARSON, C. M. Diseases of Muscle, A study in Pathology, p. 270. New York, 1953. Paul B. Hoeber. and DAVISON, C. Dystrophia 25. KESCHNER, M. myotonica. Arch. Neural. & Psych&., 30: 1260, 1933. 26. BLACK, W. C. and RAVIN, A. Studies in dystrophia myotonica. VII. Autopsy observations in 5 cases. Arch. Path., 44: 176, 1947. 27. FISCH, C. and EVANS, P. The heart in dystrophia myotonica. New England J. Med., 251: 527, 1954. I
I
and Lungs in Myotonic
Muscular
Dystrophy* PAUL J. New
CANNON,
York,
New
VOL.
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MAY
1962
York
abnormalities of the heart and lungs which were observed in eleven patients studied at the Columbia-Presbyterian Medical Center, The patients were not selected because of their cardiopulmonary problems but constitute a group either admitted to the medical wards or followed in the clinics because of their skeletal muscle disease during the years 1956-1960. Emphasis will be placed on the case histories of four of these, including two who came to autopsy, in whom the cardiac or pulmonary abnormality was a prominent feature of the clinical course.
muscular dystrophy (dystrophia myotonica) [ 11 is a familial disorder characterized by myotonia, a peculiar delay in the relaxation of contracted muscle, and by progressive muscular atrophy and wasting. The entity was originally separated from myotonia congenita in 1909 by Steinert [ 71 (hence the eponym, Steinert’s disease) and the classic clinical picture was described by Adie and Greenfield [Z] in 1923. The main features include apparent onset at about twenty to thirty years of age, muscular atrophy of the face, neck and forearm, myotonia confined to a few muscles (usually hand grasp alone) and progressive loss of tendon reflexes, in the face of unimpaired sensation. Various extramuscular phenomena contribute to the clinical picture, particularly cataracts, frontal alopecia, general wasting and testicular atrophy. In 1911 Griffith [3] provided a clinical description of a patient with dystrophia myotonica who had a pulse rate of 46 to 30 per minute; since that time an increasing number of reports have appeared describing cardiac abnormalities in patients with the disease [4]. Subsequently, Waring, Ravin and Walker [5] considered in detail the cardiovascular abnormalities in thirteen patients with this disorder, and commented on the tendency to hypotension, bradycardia and vasomotor phenomena. They also noted electrocardiographic abnormalities in six of eight patients in whom electrocardiograms were taken. More recent studies [6,7] have demonstrated the occurrence of cardiopulmonary insufficiency with alveolar hypoventilation. This clinical experience has led to the modern view that the abnormality of skeletal muscle in myotonic dystrophy is only one facet of a generalized disorder. It is the purpose of this paper to report the YOTONIC
* From the Department
M.D.
CLINICAL
SUMMARY
Table I summarizes the clinical, pulmonary and cardiovascular findings of the eleven patients. As can be seen, none were hypertensive. Eight of the eleven had electrocardiographic abnormalities (73 per cent; these included first degree heart block, atria1 flutter and ~brillation, abnormal intraventricular conduction, right and left bundle branch block, and abnormal T waves>. In two of the three patients with atria1 flutter or fibrillation, the ventricular rate was below 100 per minute even though the patients were receiving no medication. In two of the eleven patients (R. R. and K. D.) the onset of the cardiac arrhythmia anteceded recognition of the neurologic disease. Three patients had left-sided heart failure, three cardiomegaly. Only one patient (A. S.) had a murmur which was considered to be clinically significant; this was a grade 2 systolic murmur localized between the left sternal border and apex. There was no consistent correlation between the degree of electrocardiographic or cardiac abnormality and the severity of the skeletal muscular disease. Four patients had pneumonia. The one patient
of Medicine, Columbia University College of Physicians and Surgeons, and the Presbyterian Hospital, New York, New York. Manuscript received June 14,1961.
765
‘rresent
Present
Present
0
i
0
k5 yr. c&a&%; 14 yr. dyapnea; If yr. weaknnesn.un,
As life, baidness lwotonb; 3 yr mrlness; 2 montha drag& of right foot
zjegiitin
P&in,
Poeitive
‘resent
0
ktb; 3 yr. ptonis; 2yr.fbilblgYision
I5 yr. ptais, genorsliced weaknes% ewe&IlY of leg and amu
‘resent
Positive
oeumonia
IN
TABLE FUNCTION
H.B.,37, white female
of
weak-
:a&& nhouldor Birdlo, upper and lower extremity musculature; absent deep tendon refiexw; myotenia
WI,
atrophyof
PULMONARY
i.araIi~
AND
baitire
Symptoma and Dumtirm
OF CARDIAC
L B., 47, white, fednsle
andSex M.Q.,43, Nego, mlrle
.- ,.
INDICES
I PATIENTS
WTH
‘es
Normal heart and lungs
0
Normal heart and lungs
Normal heart and lunga
atiag blood ugat Iwel 147 mg. per rent
0
rlormal heart and lungs, Ghan complex
DYSTROPHY
Diabetes
MUSCULAR
0
0
WYOTONIC
-
__
. .
sinw rhythm; left axis deviation; P-R 0.18 second; QRa 0.08 second. withinnamal limits I\Tormsl
fibrillation; no axis deviation; premature WIItrioalar oontractiom from 2 foci; QI@ 0.12 meond, dot Ti.n, sin., WP. dipbasic Ta, inverted T h vs.._,; d~ycdin~n~~d Vu b1omwl sinus rhythm with no axis deltiatioq P-R 0.18 wcoad, QBa 0.w necond, S ia Vu, T inverted a%, low VW; abaormrl record with probsble termiwl intmventxicular Maduction defect ELinus bmdycsrdia; P-R 0.12 second, gas a.03 scoon&, no axis deviation: within normal sits Eiormalainoe rhythm with &St degree heart b&k; P-R 0.22 second; left nxic devi&an; left bundle branob block QRS O.l2 second I rtormai sinus rhythm; right axis deviation; P-R O.XJ second, QRS 0.09 second: within normal limits
AWi
Electrocrrk~
1
Myotonic Muscular Dystrophy-Cmwon
-
-
-
-7
-
-
-
-
-I I
P
-7
‘a
cl
-L
-
-
VOL.
32,
MAY
Myotonic
Muscular
(C. G.) with alveolar hypoventilation will be considered subsequently. The following four case histories illustrate certain cardiac and pulmonary complications of dystrophia myotonica: PATIENT K. r). (No. 733-08-07). A twenty-seven year old single Negro female domestic was admitted to Columbia-Presbyterian Medical Center for the first time on February 25, 1959, with .the chief complaint of palpitations and shortness of breath of one month’s duration. No member of the patient’s family suffered from neurologic disease. The past history was completely within normal limits except for a positive reaction to a Wassermann test ten years prior to admission. Because of this, the patient had been treated for ten days with parenteral penicillin. The patient was in good health until one year prior to admission when she noted the gradual onset of exertional dyspnea. One month prior to admission the dyspnea increased and she noted palpitations. The patient was a well nourished, well developed woman in no distress. The temperature was 98%., pulse 72 per minute and irregular, blood pressure 104/68 mm. Hg, respirations 16 per minute. The fundi were normal, the neck veins were flat. The thyroid gland was not enlarged; a firm nodule was felt in the left parotid gland. The lungs were clear to percussion and auscultation, and the heart was not enlarged. The second aortic sound was equal to the second pulmonic sound, the first mitral sound fluctuated in intensity, and a soft localized systolic murmur was heard at the apex. There was no diastolic murmur. Abdominal examination was within normal limits except for the finding of an enlarged uterus consistent with a pregnancy of three months. The erythrocyte sedimentation rate was 11 mm. in one hour; complete blood count and urinalysis were normal. A reaction to a blood serologic test for syphilis was positive while that of the cerebrospinal fluid was negative. The antistreptolysin titer was 12 units. The serum protein-bound iodine was 5.9 pg. per 100 ml. X-ray examination of the chest showed the heart and lungs to be within normal limits. Electrocardiography revealed atrial flutter with varying atrioventricular response; the atria1 rate was 300 per minute, the ventricular rate about 85 per minute. The QRS was 0.08 second and there was no axis deviation. The patient was given digitalis and maintained on digitoxin, 0.2 mg. given orally daily. Because of persistence of the arrhythmia, an attempt was made to restore normal sinus rhythm by quinidine, given orally. A total dose of 1 gm. during the first day of the trial produced no alteration in rhythm. On the second day the patient received divided doses of quinidine totaling 0.8 gm. following which the electrocardiogram revealed atria1 flutter with 2: 1 atrioventricular block, the atrial rate was 200 per minute and the ventricular rate was 100 per minute.
~ys~ophy-cu~~~~ Shortly thereafter the patient had a Stokes-Adams attack and became pulseless. She responded to vigorous pounding on the chest and the electrocardiogram again revealed atria1 flutter with 2: 1 block. This rhythm was followed by a slow nodal or His bundle rhythm with absent P waves. Four hours later the patient had ventricular fibrillation and again became unresponsive. Emergency thoractomy, cardiac massage and direct external defibrillation were successful in restoring normal sinus rhythm. Her subsequent course was uneventful. After recovery the electrocardiogram revealed a normal sinus rhythm with a rate of 81 per minute, with incomplete A-V block (prolonged P-R interval of 0.24 second). The cause of the arrythmia remained unknown. The patient was readmitted on June 2, 1959, to the obstetrical service after an episode of syncope. In the interim she had received 9.G million units of penicillin as antisyphilitic treatment. Electrocardiogram revealed sinus arrhythmia with sinus bradycardia (rate varying between 40 and 80 per minute). Incomplete A-V block appeared during the episodes of bradycardia, at which time the P-R interval increased from 0.20 to 0.24 second; minor ST-T wave changes were noted. It was then established that during the preceding year the patient had noticed difficulty in opening a clenched fist’and difficulty in seeing out of her right eye. Myopathic facies was noted, with atrophy of temporalis, masseter and orbicularis oculi muscles. The patient had a cataract in the right eye, weakness of neck flexors, mild weakness of the proxima1 muscles of both upper extremities and the shoulder girdles, and myotonia of the muscles of both hands. Reflexes were equal bilaterally, plantar responses were flexor, and sensation was intact. Electromyo~aphy confirmed the presence of myotonia. In September 1959 she was uneventfuily delivered of a normal child. She was seen again in November 1959 for resection of an asymptomatic left parotid mixed tumor. The electrocardiogram then revealed sinus bradycardia with a rate of 55 per minute and a P-R interval of 0.20 second and QRS of 0.08 second. Comment: This patient illustrates the point that a cardiac arrhythmia or other cardiac symptoms may antedate recognized disorder of skeletal muscle as manifestations of dystrophia myotonica. During the patient’s hospitalization two Stokes-Adams attacks occurred during an attempt at conversion to normal sinus rhythm from atria1 flutter with digitalis and quinidine therapy. PATSENT R. R. (No. 742-85-87). This sixty year old semiretired executive was admitted in July 1959 with the chief complaints of inability to walk of four days’ duration, and shortness of breath of four hours’ duration. The patient’s grandfather had had cataracts ABIERlCAN
JOURNAL
OF
MEDlClNE
~yotonic
Muscular dystrophy ----Canner
his father was bald; one cousin had “muscular difficulty” and his son had documented dystrophia myotonica. There was no family history of diabetes. The patient had been in good health until 1942 at which time he was hospitalized for “‘tachycardia with an irregular pulse.” At that time there was no basis for a diagnosis of hypertensive, arteriosclerotic, rheumatic or thyrotoxic heart disease. His irregular pulse persisted. In 1946, after an episode of infiuenza, he became aware of generalized weakness, and his own physician observed sluggish relaxation of his grip. A diagnosis of dystrophia myotonica was made. Subsequently, the patient noted a gradual increase in weakness. In June 1959 he was admitted to ColumbiaPresbyterian Medical Center for the first time for insertion of a suprapubic tube for relief of chronic prostatic obstruction. While in the hospital, glycosuria and a diabetic glucose tolerance curve were revealed atria1 recorded. An electrocardiogram flutter with varying degrees of A-V block, left axis deviation and right bundle branch block. The patient did well until four days prior to admission when he noted dizziness, difficulty in moving his left leg, and a low grade fever; four hours prior to admission he became extremely dyspneic. On examination the patient was an acutely ill, moderately obese man. The temperature was 101.8O~., blood pressure 84/68 mm. Hg; pulse 96 per minute and irregular, respirations 26 per minute. There was slight cyanosis of the lips and nail beds. Frontal baldness was prominent. No cataracts were noted. Examination of the fundi revealed tortuous arterioles with no other evidence of retinopathy. The neck veins were flat, the thyroid was not enlarged. There was poor thoracie expansion with diminished fremitus, dullness over the lower third of the right posterior lung where thick inspiratory rales were heard. Coarse rhonchi were evident throughout. The patient’s heart was not enlarged and the heart sounds were distant. The abdomen was normal. A suprapubic catheter was in place. Neurologic examination showed myopathic facies, generalized weakness with poor tone and atrophy of the muscles of the extremities. There was left facial weakness, a left flaccid hemiparesis, a positive Babinski sign on the left and absent deep tendon reflexes. Sensation was intact. Myotonia was present in both hands. The erythrocyte sedimentation rate was 82 mm. in one hour. The hemogram on admission was as follows: hemoglobin 16.3 gm. per cent, white blood cell count 5,100 per cu. mm., polymorphonuclear cells 87 per cent, lymphocytes 12 per cent. The blood urea nitrogen was 28 mg. per cent; a reaction to a Wassermann test was negative. The venous blood CO% content was 25 mEq. per L., and a two hour postprandial blood sugar was 171 mg. per cent. Urinalysis revealed 2-plus albumin; many white blood cells were present in the urinary sediment. A roentgenogram of the chest showed pneumonia of the VOL.
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lower lobe of the right lung and suggested slight left ventricular enlargement. Electrocardiogram showed atria1 flutter with varying A-V response, left axis deviation, right bundle branch block. The QRS interval measured 0.16 second and the ST-T wave changes were considered to be consistent with myocardial disease. Despite massive antibiotic therapy the patient pursued a downhill course. The major difficulty was his inability to raise his bronchial secretions. Repeated tracheal aspirations produced large amounts of purulent material. He died one week following admission. At postmortem examination (Autopsy No. 19,700) the changes in skeletal muscle were characteristic of dystrophia myotonica. Examination of the brain revealed recent encephalomalacia in the basilar portion of the pons and in the anterior commissure. There was moderate arteriosclerosis, but no occlusion of the vessels to the involved areas or of the right internal carotid was found. The upper right lung showed early acute bronchopneumonia. The lower lung field revealed bronchopneumonia with abscess formation, organization and several areas of granulomatous response with giant cells. The pericardial cavity contained 10 cc. of straw-colored fluid; the surfaces were clear and glistening without abnormality. The heart weighed 360 gm., all chambers were moderately dilated. The epicardium was normal in appearance as were the valves and the valve orifices. On gross inspection the myocardium appeared to be normal. The thickness of the left ventricular was 1.2 cm., that of the right ventricle 0.2 cm. The root of the aorta was dilated, and the intima showed mild arteriosclerotic change. The coronary arteries were patent throughout and there was no gross evidence of myocardial abnormality. Microscopic examination (Fig. 1) revealed minimally atherosclerotic coronary vessels. The myocardium of the left and right ventricles was histologically normal save for scattered small areas of focal subendocardial fibrosis. Section of the A-V node area failed to demonstrate an anatomic lesion. The Purkinje tissue was normal. Comment: The patient had a cardiac arrhythmia approximately four years prior to the onset of weakness and the diagnosis of dystrophia myotonica. Thus, cardiac symptoms and signs preceded evidence of muscular disease. During this hospitalization, left ventricular prominence was noted on roentgenogram, and atria1 flutter with varying A-V response, right bundle branch block and non-specific changes of myocardial disease were found on electrocardiography. Inability to raise bronchial secretions, presumably as a result of weakness of the thoracic musculature, complicated management of his
770
Myotonic Muscular Dystrophy-Cannon
FIG. 1. Patient R. R. Microscopic section erate atherosclerosis of a coronary vessel.
terminal. pneumonia. Examination of the heart at autapsy failed to provide an anatomic basis for the electrocardiographic abnormalities. PATIENT C. G. (No. 92-20-85). A sixty-four year old Cuban-born’ man was admitted to ColumbiaPresbyterian Medical Center for the fourth time in February 1960 for regulation of his diabetes. The patient’s brother, son and two nephews were said to have dystrophia myotonica. In 1937 the patient was seen at another hospital because of weakness and poor general coordination. A diagnosis of dystrophia myotonica was made, and the patient was treated for a short while with quinine, which was discontinued because of its failure to augment his muscular strength. A progressive disturbance of gait, speech and swallowing ensued during the subsequent years. In 1957 the patient was admitted to Columbia-Presbyterian Medical Center for the first time because of generalized weakness. The venous blood COa content was 33 mEq. per L. The hemoglobin was 16.3 gm. per cent. The fasting blood sugar was 103 mg. per cent. The chest roentgenogram was within normal limits. In 1957, because of complaints of dyspnea and orthopnea with the finding of cardiomegaly, the patient was given digitalis. In 1958 he was admitted because of pneumonia; at this time his two hour postprandial sugar level was 200 mg. per cent. Because of increasing glycosuria the patient was readmitted for diabetic regulation in February 1960. On physical examination the patient appeared chronically ill. Baldness was noted. The temperature was 98%., pulse 80 per minute, blood pressure 120/60 mm. Hg; respirations 18 per minute. The extraocular movements were normal. Fine dust-like
of the left ventricle
revealing
mod-
particles were noted in the posterior one-third of each lens. The fundi were normal. The thyroid was not enlarged and the neck veins were flat. Thoracic expansion was poor, breath sounds were distant, and no rales were heard. The left border of cardiac dullness was 1 cm. to the left of the mid-clavicular line in the sixth intercostal interspace. The second aortic sound was equal to the second pulmonic sound. There was a localized, grade 1 apical systolic murmur. Abdominal examination was within normal limits. There was marked atrophy of the facial muscles, of the sternocleidomastoids, and of the musculature of the extremities. Cyanosis of lips and of the nail beds was evident. There was no clubbing of the fingers. Deep tendon reflexes were equal and the plantar responses were flexor. Hair distribution was normal. The testicles were small. The erythrocyte sedimentation rate was 5 mm. in one hour. The hemogram was as follows: hemoglobin 18.6 gm. per cent, hematocrit 57 per cent, white blood cell count 7,900 per cu. mm. with a normal differential. &inalysis revealed a Specific gravity of 1.014, with l-plus glucose. The blood urea nitrogen was 16 mg. per cent, and the two hour postprandial blood sugar level was 243 mg. per cent. A chest roentgenogram revealed clear lung fields except for a minute area of fleck-like atelectasis at the right base, and moderate cardiomegaly with a cardiac contour suggestive of left ventricular enlargement. Electrocardiogram showed sinus rhythm at a rate of 75 per minute with incomplete A-V block (prolonged P-R of 0.24 second) and rare premature ventricular contractions, left axis deviation, intraventricular conduction defect with a QRS of 0.14 second. Arterial blood studies revealed an oxygen saturation of 78 per Cent, pH 7.39, hematocrit 48.3 per cent, Cop content 70 AMZRICAN
JOURNAL
OR
MEDICINE
Myotonic
Muscular
volumes per cent, CO2 tension of 62 mm. Hg. The patient’s diabetes was controlled with Orinase.@ He signed out of the hospital before pulmonary studies could be completed.
Comment: This rence
dystrophy. lips
and
fingers, breath
polycythemia, an
diagnosis
was based
diminished arterial
pCOz
cardiomegaly, interval,
poor
clear
oxygen
of left-sided and
ventricular
also
hypo-
of cyanosis expansion, lung
fields,
unsaturation Hg. heart
the
occur-
myotonic
alveolar
thoracic
of 62 mm.
intraventricular
premature
of
the in
on the findings sounds,
arterial
was his history
illustrates
hypoventilation
The
ventilation of
patient
of alveolar
failure
increased
conduction contractions
and
Of note also
defect found
and
P-R and on
electrocardiography. PATIENT M. G. (No. Z-93-08). This forty-three year old Negro mechanic was admitted to the Columbia-Presbyterian Medical Center for the first time in 1955 following a clinic study of epigastric pain. The patient was well until 1945, at which time he noticed weakness of the right leg and of the hands, which progressed during the ensuing years making it difficult for him to obtain jobs. In 1952 a lymphoepithelioma of the pharynx was treated successfully with 20,900 roentgens in air. In 1956 he was seen in the clinic with a history of two years of postprandial mid-epigastric pain (relieved by taking alkali) and a 30 pound weight loss. No history of hypertension, angina, rheumatic fever, diphtheria, myocarditis or other cardiac difficulty was elicited. Ear, nose and throat examination was within normal limits. A chest roentgenogram showed generalized cardiomegaly. Electrocardiography revealed atria1 fibrillation with multifocal ventricular premature contractions, a ventricular rate of approximately 60 per minute, a QRS complex of 0.12 second and a Q-T interval of 0.43 second. Low T waves were present in leads I, aVL and V+ Gastrointestinal series revealed a “neurogenic disturbance of swallowing” and an ulcer of the lesser curvature of the stomach. The patient was admitted to the hospital. On physical examination the patient was an emaciated, chronically ill man with dysarthric speech. The vital signs were temperature, normal; blood pressure 100/60 mm. Hg; pulse 62; respiraticns, normal. The patient had bilateral cataracts, normal fundi and was without distended neck veins or thyromegaly. The lungs were clear. The left border of cardiac dullness was halfway between the mid-clavicular and anterior axillary lines. The second aortic sound was greater than the second pulmonic sound, and there were no murmurs. Abdominal examination was within normal limits. There was testicular atrophy. There was atrophy of the facial muscles, of the
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shoulder girdle muscles and of the musculature of the upper and lower extremities. The patient had generalized muscular weakness, inability to relax his grip, and diminished to absent deep tendon reflexes. The sensory examination was within normal limits. The erythrocyte sedimentation rate was 55 mm. in one hour. The hemoglobin was 9.5 gm. per cent; urinalysis was normal. The blood urea nitrogen was 28 mg. per cent. A two hour postprandial blood sugar was 83 mg. per cent. The basal metabolic rate was -39 per cent. Radioactive iodine uptake was 22 per cent at twenty-four hours. The serum cholesterol was 173 mg. per cent. A prostigmine test result was negative. It was concluded that the patient had dystrophia myotonica, gastric ulcer and cardiac disease of uncertain etiology. He responded symptomatically to an ulcer regimen and there was radiologic evidence of ulcer healing. After three months, however, roentgenograms suggested the development of a new gastric ulcer on the lesser curvature. In January 1957 the patient had shortness of breath, marked orthopnea, cough and hemoptysis. On admission he was found to be acutely ill with a temperature of 103’F., an apical pulse of 150 per minute, blood pressure 11 O/60 mm. Hg, and respirations of 30 per minute. Roentgenograms revealed a moderately enlarged heart with a prominent pulmonary artery segment. The lungs were congested bilaterally and a density noted in the lower right lung field suggested bronchopneumonia; in this area clinically coarse inspiratory rales were heard. Staphylococcus aureus was cultured from the patient’s sputum. The white blood cell count rose to 22,000 per cu. mm. He was treated with antibiotics and digitalis. Electrocardiography at this time showed atria1 fibrillation with a ventricular rate of 80 per minute, no axis deviation, and frequent premature ventricular contractions from two foci. Since the previous tracing, T waves in leads II, aVF and V4 had become flat, and inverted in leads Vs and Vs. After a period of initial improvement, on the fifth hospital day he passed a guaiac positive stool. Although it was suspected that he was bleeding from a gastric ulcer, it was decided to treat him supportively because of his poor general condition. Despite transfusions he continued to have episodes of hypotension, vomiting, coughing and hemoptysis. On January 17, 1957, the patient died. Postmortem examination (Autopsy No. 18,663) revealed skeletal muscle characteristic of dystrophia myotonica, associated with cataracts, testicular atrophy and frontal alopecia. Focal atrophy and gliosis were present in the right superior gyrus and right hippocampus. There were gastric ulcers with secondary massive gastrointestinal hemorrhage. Examination of the lungs revealed “generalized congestion and moderate edema fluid, and there was organizing and resolving pneumonia which in some areas had elicited a slight giant cell foreign body response.” The pericardial cavity contained about
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Fro. 2. Patient M. G. Microscopic section of the left ventricular myocardium of patient. A distinct cardiomyopathy analogous to the degeneration of skeletal muscle which occurs in myotonic muscular dystrophy is apparent. 50 cc. of pale yellow fluid and the surfaces were
smooth and glistening. The heart weighed 600 gm.,
the epicardium was smooth and the usual amount of epicardial fat was present. All the cardiac chambers appeared to be somewhat dilated. The endocardium was smooth and glistening. The valves were delicate and the valve dimensions were normal. The myocardium of the right and left ventricles appeared to be somewhat thickened; left ventricle 2.5 cm., right ventricle 0.4 cm., but the myocardium of the atria appeared thin and of a firm consistency. The coronary vessels arose and were distributed normally; the vessels were widely patent throughout and were entirely free of atheromatous clot or intimal thickening. Microscopic examination of the heart (Fig. 2) revealed prominent interstitial edema with a slight increase in the interstitial connective tissue. There were small areas of focal interstitial fibrosis and about these areas the myocardial fibers appeared atrophic and/or necrotic. There were also occasional minute areas in which the myocardial fibers seemed to have dropped out. In these there was a loose meshwork of fibroblasts and lymphocytes and the surrounding myocardial fibers appeared somewhat atrophic. There was marked variation in fiber size and a great majority of the surrounding fibers exhibited hyper-
trophy. The myocardial nuclei also varied considerabIy in size, and were frequently large and pyknotic. Comment: This forty-three year old patient with moderately advanced dystrophia myotonica had evidence of extensive cardiac abnormality when first seen, i.e., atria1 fibrillation,
intraventricular conduction defect, muftiple ventricular premature contractions, cardiomegaly and, terminally, left-sided congestive heart failure. Striking histologic changes of the myocardium were present. COMMENTS
Significant abnormalities of the heart and lungs are apparent in this series of eleven patients with dystrophia myotonica. The pulmonary complications of the disease consisted of repeated episodes of pneumonia and, in one instance, of alveolar hypoventilation; the cardiac complications included electrocardiographic abnormalities, arrhythmias, Stokes-Adams attacks and left-sided heart failure. A distinct cardiomyopathy was demonstrated in one patient at autopsy. Pulmonary Complicatioas. In two of the four patients with pneumonia, the pneumonitis occurred during the terminal illness. Muscular weakness with a resultant diminished cough reflex and retention of bronchial secretions undoubtedly contributed to the poor response to antibiotic administration. No characteristic pulmonary abnormality has been noted in myotonic dystrophy at postmortem examination. Other than pneumonia in both, and congestion in one, the lungs of two autopsied patients herein described were non-contributory. Alveolar hypoventilation was present in one AMERICAN
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Myotonic Muscular Dys~ophy-Gu~~~~ patient (C. G.). This may be the result of insufficient ventilatory drive at one of four sites [8]. The defect may occur in: (1) The stimulus to respiration; (2) the respiratory center; (3) neuromuscular coordination or; (4) in the action of the chest bellows. In recent years clinical studies of patients with the syndrome of alveolar hypoventilation caused by defects at each of these various sites have been reported [o-74]. In myotonic dystrophy the defect appears to lie in the action of the chest bellows. Bashour et al. [I4 reported the case of a fifty-seven year old man with myotonic dystrophy who presented with polycythemia and cyanosis; he was found to have pulmonary function abnormalities suggestive of inadequate alveolar ventilation. Kilburn et al. [S] described a thirty-one year old man with dystrophia myotonica and mild obesity who showed marked somnolence, cyanosis and CheyneStokes breathing. Studies of this patient revealed a diminished vital capacity and a small expiratory reserve capacity and total lung capacity. The maximum breathing capacity was reduced to less than half of the predicted value. Arterial oxygen saturation ranged between 80 and 89 per cent and rose to 96 per cent after inhalation of 100 per cent oxygen for five minutes. The arterial pC0~ ranged from 56 to 60 mm. Hg, and the pH from 7.30 to 7.35. These findings were considered to be consistent with alveolar hypoventilation. Additional investigation by these workers [7] in nine other patients with dystrophia myotonica yielded similar results: reduction in total lung capacity, vital capacity and maximum breathing capacity, reduced minute ventilation, retention of CO2 and systemic arterial hypoxemia. These changes were attributed to the limited expansion of the chest bellows arising from weakness of the thoracic muscles and of the diaphragm [%?I. Myotonia of these structures, by increasing the work of breathing, could also contribute to the production of alveolar hypoventilation. One patient [77] has been described who, on fluoroscoPy> showed diminished excursions and irregular jerking movements of the diaphragm on ascent and descent, which raised the question of myotonia of the diaphragm; this patient also exhibited myotonia of the intercostal muscles on electromyography. In common with all other types of hypercapnea, the ventilatory response to carbon VOL.
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dioxide inhalation in patients with myotonic dystrophy and the hypoventilation syndrome was demonstrated to be subnormal 173. In contrast with another group of patients with progressive muscular dystrophy, Kilburn et al. [7] noted that the breathing of 100 per cent oxygen was accompanied by a fall in resting minute ventilation in patients with dystrophia myotonica, despite only mild hypercapnea. This observation led these authors to postulate a respiratory center depression in the disease, in addition to the obvious thoracic wall dysfunction. However, such a thesis is difficult to validate in the presence of abnormal chest mechanics [ 73,741. Cardiac ~O~~liG~~~o~s. Eight of the eleven patients described had abnormal electrocardiograms. Several observers since Griffith [3] have commented on the incidence of arrhythmias and electrocardiographic abnormalities in dystrophia myotonia. Evans [78] in 1944 noted prolonged P-R intervals in ten of thirteen patients, Spillane [19] in 1951 described sixteen patients in whom electr~ardio~aphic studies revealed low voltage T waves in eight patients, a P-R interval longer than 0.20 second in six, and slurring of the QRS complex in four. In reviewing the literature on this subject in 1951, Fisch [ZO] summarized the electrocardiographic findings in eighty-five described patients, and in 68 per cent of these, significant abnormalities were found. In 91 per cent of this group the alteration consisted of a conduction defect or a disturbance of rhythm, or both. Forty-eight per cent of the patients showed an alteration of the P-R interval, 12 per cent a prolonged QRS complex. Atria1 flutter or fibrillation was present in 2 per cent. Other abnormalities occurred but these were less frequent. Moreover, the frequency of electrocardiographic abnormalities did not vary significantly among the various age groups from twenty to over fifty years of age. The high incidence of electrocardiographic changes, and the absence of age-dependence, led Fisch to suspect that these changes were a part of myotonic dystrophy rather than a coincidental finding. One patient (K. D.), when first hospitalized had two apparent Stokes-Adams attacks; the second was secondary to ventricular fibrillation. The role of quinidine therapy in causing her attacks is speculative. In favor of the view that the drug was toxic to an abnormal myocardium
774
Myotonic Muscular Dystrophy-Camon
is the report of one patient with myotonic dystrophy and intermittent atria1 fibrillation who was given quinidine in an attempt to restore normal sinus rhythm [S]. Administration of the drug was associated with hypotension on one occasion and with paroxysmal ventricular tachycardia on another. Stokes-Adams attacks occur in untreated dystrophia myotonica. Brain [27] states that complete heart block has been seen in the disease. One of Evans’ [78] thirteen patients had two probable Stokes-Adams attacks with an interval electrocardiogram revealing a P-R interval of 0.30 second and an atypical bundle branch block. Litchfield [Z?] describes a fortytwo year old woman with dystrophia myotonica who presented with seven years of Stokes-Adams attacks causing unconsciousness, and no other cardiac symptoms. Electrocardiography showed varying degrees of A-V conduction from sinus bradycardia to complete A-V block. The ventricular complex, always abnormal, varied from right bundle branch block to left bundle branch block indiscriminately; an electrocardiogram taken during one attack while the patient was in the hospital showed probable ventricular tachycardia which, on recovery, was followed by complete A-V block. Other cardiovascular abnormalities are Iess common but can be clinically significant. In the present series these included cardiomegaly and left-sided heart failure. Similar reports have been published by others. “Sudden and unexpected death from heart failure” in a patient with myotonic dystrophy prompted Spillane’s [79] report. Cantwell [23] reported a thirty-six year old woman who first presented with left ventricular failure and pneumonia. The association of left-sided congestive heart failure, electrocardiographic conduction defect together with cataracts raised the clinical suspicion which led to neurologic evaluation and the eventual diagnosis of dystrophia myotonica. Evans [ 781 in 1944 had suggested that cardiovascular findings contribute to the earlier and easier diagnosis of this disease. The cardiac changes found at postmortem in one patient (M. G.) were distinctive and provided ample explanation for this heart failure. They resembled the characteristic changes in skeletal muscle in myotonic dystrophy [Za], i.e., enlargement of scattered muscle fibers with centrally placed muscle nuclei, isolated fibers with nuclear proliferation, and staining of
cytoplasm. In the late stages atrophy is prominent, with rows and clusters of dark-staining nuclear remnants lying in connective tissue and between fat cells. Few pathologic studies on heart muscle in this disease have appeared in the literature. Keschner and Davison [ZZj in 1933 noted in one patient that the myocardium was better preserved than the striated musculature: “the muscle fibers of the right ventricle were replaced by fat”. . . (there was) “destruction of single muscle fibers with fatty replacement, increase in sarcolemma nuclei and loss of striation.” The heart is mentioned briefly in five autopsied cases by Black and Ravin [.%I. All were within normal limits on gross examination. One heart showed “moderate variability in size of fibers with variation in nuclear size and shape.” Only left ventricular dilatation was noted in a patient of Spillane [ 191 who died from sudden ventricular failure. Fisch and Evans [27] in 1954 related in some detail the pathologic findings in a forty-one year old man with myotonic muscular dystrophy who had no cardiac symptoms or cardiomegaly but did have atria1 flutter and varying A-V block. The patient died suddenly. At postmortem the lungs were severely congested and edematous; the heart was soft and flabby, and weighed 340 gm. The coronary vessels were normal as were the valves and valve leaflets. The walls of the left and right ventricles were 1.2 and 0.4 cm. thick, respectively, with a few small hemorrhagic and mottled gray areas scattered throughout the myocardium. On microscopic examination the left atrium showed a moderate amount of fatty infiltration; sections of the myocardium revealed “diffuse fibrosis with separation of muscle fibers by fairly dense fibrous connective tissue. Hypertrophied muscle fibers with large rectangular nuclei were scattered throughout.” In one patient (R. R.) the heart was found to be normal (including the A-V node) except for moderate coronary arteriosclerosis and small areas of subendocardial fibrosis which might be expected in a patient of this age. Another patient (M. G.) had normal coronary arteries and valves. histologically, the myocardium showed changes which resembled an earlier stage of the lesion described by Fisch and Evans. Undoubtedly, such changes are unusual. However, they may represent anatomically a more severe degree of deranged myocardial metabolism than was present in the described patients with AMERICAN
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Muscular
myotonic dystrophy who had lesser cardiac abnormalities (arrhythmias and/or conduction defects) and no histologic changes in the myocardium. The possibility exists that the disturbances of cardiac function and cardiac anatomy noted in patients with dystrophia myotonica are, along with cataracts, baldness, and testicular atrophy, genetically determined manifestations of an inherited disorder which most obviously affects skeletal muscle. SUMMARY
Cardiac and pulmonary manifestations are reported in a group of eleven patients with myotonic muscular dystrophy. The detailed case histories of four patients in whom abnormality of the heart or lungs was prominent are presented. The pulmonary complications, frequent pneumonias and development of the syndrome of alveolar hypoventilation, are discussed. The cardiac complications, abnormal electrocardiograms, arrhythmias, Stokes-Adams attacks and left ventricular failure, are enumerated and the pertinent literature is reviewed. The postmortem findings in two of the patients are presented. In one there was a distinct cardiomyopathy analogous to the degeneration of skeletal muscle which occurs in the disease. It is suggested that the cardiopathy seen in dystrophia myotonica represents, along with atrophy of skeletal muscle, baldness, cataracts, another genetically determined manifestation of this hereditary disorder. REFERENCES
1. STEINERT, H. Uber das klinische und anatomische Bild des Muskelschwundes der Myotoniker. Deutsche Ztschr. Nervenh., 37: 38, 1909. 2. ADIE, W. J. and GREENFIELD,J. G. Dystrophia myotonica. Brain, 46: 73, 1923. 3. GRIFFITH, T. W. On myotonica. Quart. J. Med., 5: 229, 1911. 4. GUILLAIN, G. and ROUGUES, L. Le coeur dans la myotonie atrophique. Ann. mid., 31: 158, 1932. 5. WARING, J., RAVIN, A. and WALKER, C. Studies in dystrophia myotonica. II. Clinical features. Arch. Znt. Med., 65: 763, 1940. 6. KILBURN, K. H., EACAN, J. T. and HEYMAN, A. Cardiopulmonary insufficiency associated with myotonic dystrophy. Am. J. Med., 26: 929, 1959.
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7. KILBURN, K. H., EAGAN, J. T. and SIEKER, II. Cardiopulmonary insufficiency in myotonic and progressive muscular dystrophy. New England J. Med., 261: 1089,1959. 8. FISHMAN, A. P., TURINO, G. M. and BERGOFSKY, E. H. Editorial: The syndrome of alveolar hypoventilation. Am. J. Med., 23: 333, 1957. E. J., TURINO, G. M. and FISHMAN,A. P. 9. BERGOFSKY, Cardiorespiratory failure in kyphoscoliosis. il4edicine, 38: 263, 1959. 10. LUK,Q, D. S. and PLUM,F. Pulmonary function in patients convalescing from acute poliomyelitis with resoiratorv naralvsis. Am. J. Med., 12: 388, 1952. 11. CARROLL, D: ‘A peculiar type of c&diopulmonary failure associated with obesity. Am. J. Med., 21: 819, 1956. 12. BURWELL, C. S., ROBIN, E. D., WHALEY, R. D. and BICKELMANN,A. F. Extreme obesity associated with alveolar hypoventilation: A Pickwickian syndrome. Am. j: Med., 21: 811, 1956. 13. RICHTER. T.. WEST. J. R. and FISHMAN.A. P. The syndrome of alveolar hypoventilation and diminished sensitivity of the respiratory center. New England J. Med., 256: 1165, 1957. 14. RODMAN,T. and CLOSE,P. The primary hypoventilation syndrome. Am. J. Med., 26: 808, 1959. 15. BASHOUR, F., WINCHELL, P. and REDDINGTON,J. Myotonia atrophica and cyanosis. New England J. Med., 252: 768, 1955. 16. CAUGHEY,J. E. and GRAY, W. G. Unilateral elevation of diaphragm in dystrophia myotonica. Thorax, 9: 67, 1954. 17. BENAIM, S. and WORSTER-DROUGHT, C. Myotonic dystrophy with myotonia of the diaphragm causing pulmonary hypoventilation with anoxaemia and secondary polycythemia. M. Zllus., 8: 221, 1956. 18. EVANS, W. The heart in myotonia atrophica. Brit. Heart J., 6: 41, 1944. 19. SPILLANE, J. D. The heart in myotonia atrophica. Brit. Heart J., 13: 343, 1951. 20. FISCH, C. The heart in dystrophia myotonica. Am. Heart J., 41: 525, 1951. 21. BRAIN, R. Diseases of the Nervous System, 5th ed., p. 843. London, 1956, Oxford University Press. 22. LITCHFIELD, J. A. A-V dissociation in dystrophia myotonica. Brit. Heart J., 15: 357, 1953. 23. CANTMTELL,D. and HICKEY, K. Dystrophia myotonica with cardiac symptoms. Irish J. M. SC., 6: 360, 1954. 24. ADAMS, R. D., DENNY-BROWN, D. and PEARSON, C. M. Diseases of Muscle, A study in Pathology, p. 270. New York, 1953. Paul B. Hoeber. and DAVISON, C. Dystrophia 25. KESCHNER, M. myotonica. Arch. Neural. & Psych&., 30: 1260, 1933. 26. BLACK, W. C. and RAVIN, A. Studies in dystrophia myotonica. VII. Autopsy observations in 5 cases. Arch. Path., 44: 176, 1947. 27. FISCH, C. and EVANS, P. The heart in dystrophia myotonica. New England J. Med., 251: 527, 1954. I
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