Heart Block in Kearns-Sayre Syndrome

Eng! J Med 290:1413-1420, 1458-1469, 1974 4 Pilch YH, Myers GH, Sparks FC, et al: Prospects for the immunotherapy of cancer. Curr Probl Surg Jan : l-46, Feb 1-61, 1975 5 Morton DL, Eilber FR, Holmes EC, et al: BCG immunotherapy of melanoma: Summary of a seven year experience. Ann Surg 180:635-643, 1974 6 Sparks FC, O'Connell TX, Breeding JH, et al: BCG immunotherapy given as an adjuvant to operation: Prevention of death from metastases from mammary adenocarcinoma in rats. J Nat! Cancer lnst 53: 1825-1826, 1974 7 Gutterman JU, Mavligit G, Gottleib ], et a!: Chemoimmunotherapy of disseminated malignant melanoma with dimethyl triazeno imidazole carboxomide ( DTIC) and bacillus Calmette-Guerin ( BCG) . N Eng! J Med 291:592-597, 1974 8 Eilber FR, Morton DL: Impaired immunologic reactivity and recurrence following cancer surgery. Cancer 25:362367, 1970 9 Sparks FC: BCG in cancer treatment. N Eng! J Med 290:343, 1973 10 McKhann CF, Hendrickson CG, Spitler LE, et al: Immunotherapy of melanoma with BCG: Two fatalities following intralesional injection. Cancer 35:514-520, 1975 11 Levy NL, Mahaley MS Jr, Day ED: Serum-mediated blocking of cell-mediated anti-tumor immunity in a melanoma patient: Association with BCG immunotherapy and clinical deterioration. lnt J Cancer 10:244-248, 1972 12 Bornstein RS, Mastrangelo MJ, Sulit H, et al: Immunotherapy of malignant melanoma with intralesional BCG. Nat! Cancer Inst Monogr 39:213-220, 1973 13 Sparks FC, Breeding JH : Varied effects of immunotherapy with BCG and tumor regression and enhancement resulting from immunotherapy with bacillus Calmette-Guerin and neuramidinase. Cancer Res 34:32623269, 1974 14 Baier RL, Levine BB : Adverse cutaneous reactions to drugs. In Dermatology in General Medicine (Fitzpatrick TB, Arndt KA, Clark WH, et al eds). New York, McGrawHill Inc, 1971, p 1282

Heart Block m Kearns-Sayre Syndrome* Electrophysiologic-Pathologic Correlation DanielS. Clark, M.D.; Robert]. Myerburg, M.D.; Azorides R. Morales, M.D.; Benjamin Befeler, M.D., F.C.C.P.; Francisco A. Hernandez, M.D., F.C.C.P.; and Henry Gelband, M.D.

A 13-year-old boy with Keams-Sayre syndrome, consisting of retinitis pigmentosa, external ophthalmoplegia, and myocardial fibrosis, ls presented. A review of the clinical findings and electrocardiographic changes over a period of three years showed progressive atrioventricular and intraventricular conduction-system distur°From the Departments of Pediatrics, Medicine, and Pathology, University of Miami School of Medicine, Miami. Reprint requests: Dr. Myerburg, University of Miami School of Medicine, PO Box 520876 Biscayne Annex, Miami 33152

CHEST, 68: 5, NOVEMBER, 1975

bances. Electrophysiologic documentation by His bundle recordings localized the atrioventricular (A V) block distal to the A V node. Postmortem examination revealed microscopic degeneration and fibrosis in the distal portion of the bundle of His and the right and left bundle branches. An approach to cardiac evaluation and therapy ls discussed.

T

he clinical triad of retinitis pigmentosa, external ophthalmoplegia, and complete heart block was initially described in 1958. 1 The ominous prognostic importance of the cardiac lesion in this syndrome was stressed by Keams in 1965. 2 Subsequently, progression of documented disturbances in cardiac conduction lead-

For editorial comment, see page 614 ing to symptomatic heart block and death 2 • 3 has been reported in some cases, but there have been no electrophysiologic-pathologic correlations to date. In the patient presented in this report, His bundle recordings localized the site of heart block distal to the atrioventricular (A V) node, and this was eventually confirmed at postmortem examination with identification of fibrotic lesions in the His bundle and proximal bundle branches. CASE REPORT

A ten-year-old white boy was first seen at the University of Miami Hospitals in 1968 for the evaluation of bilateral ptosis of the eyelids of four years' duration, proximal myopathy, and external ophthalmoplegia. He weighed 29 kg ( 64 Ib) and was 130 em ( 4 ft 3 in) tall. Vital signs were within normal limits. Ophthalmologic examination revealed bilateral ptosis, marked external ophthalmoplegia with severely restricted horizontal and vertical eye movements, and retinitis pigmentosa. Neurologic abnormalities consisted of impaired function of cranial nerves 3, 4, and 6; mild motor weakness of the muscles of the upper extremities, masseter, and pterygoid muscles; symmetric hyporeflexia; and cerebellar dysmetria. Cardiac examination revealed no abnormalities. The electrocardiogram showed normal sinus rhythm with complete right bundle branch block and left anterior hemiblock ( Fig 1 ) . Deltoid muscle biopsy disclosed scattered necrotic muscle fibers consistent with a myopathy. The electroencephalogram was normal. During the following three years, the physical findings remained constant until the patient experienced an episode of dizziness and syncope for which he was hospitalized. The pulse rate at this time was 40 to 50 beats per minute with premature contractions. ECG demonstrated sinus bradycardia with complete right bundle branch block, left anterior hemiblock, and premature atrial extrasystoles. Subsequent electrocardiographic recordings demonstrated short periods of 2 :1 and 3 :1 AV block. A right heart catheterization was within normal limits. A His bundle recording (Fig 2) demonstrated a very prolonged His-ventricle ( H-V) interval ( 105 msec) of the conducted beats, with 2: I infra nodal AV block. Thus, the electrophysiologic picture was that of trifascicular block, consisting of complete right bundle branch block (prolonged QRS duration of 140 msec), left anterior hemiblock (abnormal left axis deviation), and a prolonged HV interval ( 105 msec), suggesting delayed conduction in

HEART BLOCK IN KEARNS-SAYRE SYNDROME 727

I

T'

-

•

V4

ft

V5

I

-

Ill

Vl

V3

V6

FIGURE l. Scalar 12-lead ECG demonstrating normal sinus rhythm, complete right bundle branch block, and left anterior hemiblock. Atrial rate, 60; ventricular rate, 60; P-R interval, 0.20 sec; QRS duration, 0.14 sec; and QRS axis, -60• .

either the distal His bundle or the posterior division of the left bundle branch . Because of the syncope and electrophysiologic changes, a permanent demand transvenous ven-

tricular pacemaker was inserted, which resulted in improvement in the clinical symptoms. The patient remained well for five months. He was then hospitalized again because of the

ATRIAL RATE ' 89 per min ( P. P. 680 m sec) QRS 140 msec AH 65 msec HV 105 msec

II

AH

v.

AH

A

v

HBE

RVE I sec

4-17-72

BB 1001

2. His bundle recording. Simultaneous recording of His bundle electrogram ( HBE) and standard lead 2 ( II) demonstrated Mobitz 2 infranodal 2 : 1 AV block and trifascicular bundle branch block. Trifa~cicular block is shown by complete right bundle branch block (prolonged QRS duration, 140 msec), left anterior hemiblock (abnormal left axis deviation), and prolonga-· tion of the H-V interval ( 105 msec) . RVE, right ventricular electrogram. FIGURE

728 CLARK ET AL

CHEST, 68: 5, NOVEMBER, 1975

sudden onset of polyuria, polydipsia, dehydration, and disorientation considered to represent diabetic ketoacidosis, presumably precipitated by the steroid therapy he had been receiving for his myopathy. Shortly after admission, cardiopulmonary arrest occurred, and the patient could not be resuscitated. Postmortem examination revealed widespread spongy degeneration of the cerebral white matter, basal ganglia, brain stem, and cervical spinal cord. Prominent histopathologic changes were present in the skeletal muscles of the upper and lower extremities, neck, and shoulder girdle and in the abdominal wall, intercostal muscles, diaphragm, and ocular muscles. These changes, which were more pronounced in the ocular muscles, consisted of severe atrophy with granul~rity and vacuolization of muscle fibers, loss of cross striations, and proliferation of sarcolemmic nuclei. Muscle fibers showed considerable variation in size and shape and an increase in interstitial connective tissue. The heart weighed 190 gm and showed no gross structural abnormalities. The coronary arteries arose in their normal positions and were grossly normal. The tricuspid, pulmonic, mitral, and aortic valves measured 10.2, 6.4, 9.5, and 5.0 em, respectively, and their leaflets were thin and pliable. The plastic-coated pacemaker wire was found embedded within the columnae cameae of the right ventricle. The endocardium was thin and smooth throughout, except for minimal thickening in the subaortic area. The myocardium was pale brown. The ventricular wall measured 0.3 on the right and 1.3 em on the left. Microscopic examination showed no abnormalities of the working myocardium. The cardiac conduction system was dissected and serially sectioned following previously reported techniques.4.11 Sinus and AV nodes were normal. However, extensive changes were present in the distal portion of the bundle of His extending to the origin of the bundle branches. In these segments of the specialized tissue, the muscle fibers varied slightly in size and were vacuolated and replaced to a great extent by fibrous connective tissue and adipose tissue without an inflammatory cell reaction ( Fig 3 and 4).

em

FIGURE 3. Marked segmental degeneration of bundle of His (arrow) . F, Central fibrous body; VS, ventricular septum (hematoxylin-eosin, original magnification X 27 ) .

DISCUSSION

FIGURE 4. Extensive fat infiltration in proximal portion of left bundle branch ( LBB) . RBB, Right bundle branch ( hematoxylin-eosin, original magnification X 65 ).

CHEST, 68: 5, NOVEMBER, 1975

The clinical triad of retinitis pigmentosa, external ophthalmoplegia, and cardiomyopathy as described by Keams and Sayre 1 in 1958 has been reported in adolescents and young adults. There is equal sex distribution and no apparent hereditary influence. Frequently assoCiated with the syndrome is weakness of facial and peripheral muscles, deafness, small stature, abnormal electroencephalographic findings, and increased protein level of the cerebrospinal fluid. The central role played by the cardiomyopathy in the syndrome has already been mentioned. 2 As in our case, it is not unusual to note progression of the conduction abnormality to the point of clinical symptoms. 2 • 3 •6 • 7 At least two deaths have been attributed to sudden complete heart block. 2,a Partial bilateral bundle branch block (right bundle branch block and left anterior hemiblock) is a common finding in this syndrome. It often precedes the development of symptomatic high-degree AV block. His bundle studies 8 and pathologic studies 9 • 10 of partial bilateral bundle-branch block in other clinical settings have demonstrated extensive involvement of both bundle

HEART BLOCK IN KEARNS-SAYRE SYNDROME 729

branches. Morriss et al 6 have described His bundle findings in one patient with this syndrome; and, as in our case, they showed extensive His-Purkinje system disease ( trifascicular block and Mobitz 2 AV block). Among the 16 cases we have found in the literature, 1 • 3 •6 ·7 · 11 pathologic studies have been infrequent.'· 3 In these few cases, no abnormalities have been described in the cardiac conduction system to explain the clinically observed conduction abnormality, prior to the present case report. The focal nature of the changes, limited to the distal His bundle and proximal bundle branches, emphasize the necessity for meticulous histologic examination of the entire conduction system. Clinical evaluation of the site 1 2 • 13 and the extent 8 of the conduction system impairment is available by means of the routine scalar ECG and the His-bundle catheter method. 14 Such detailed studies should assist the physician in determining the appropriate time to insert a demand transvenous pacemaker. REFERENCES

2

3

4 5 6 7 8

9 10

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12

13 14

Kearns TP, Sayre GP: Retinitis pigmentosa, external ophthalmoplegia and complete heart block. Arch Ophthalmol 60:280, 1958 Kearns TP : External ophthalmoplegia, pigmentary degeneration of the retina and cardiomyopathy: A newly recognized syndrome. Trans Am Ophthalmol Soc 63:559, 1965 Jager BV, Fred HL, Butler RB, et al: Occurrence of retinal pigmentation, ophthalmoplegia, ataxia, deafness and heart block. Am J Med 29:808, 1960 James TN: Anatomy of the human sinus node. Anat Rec 141 : 109, 1961 James TN : Morphology of the human atrioventricular node, with remarks pertinent to its electrophysiology. Am Heart J 62:756, 1961 Morriss JH, Eugster GS, Nora ]J, et al: His bundle recording in progressive external ophthalmoplegia. J Pediatr 8l :ll67, 1972 Uppal SC: Keams' syndrome, a new form of cardicr myopathy. Br Heart J 35:766-769, 1973 Narula OS, Samet P : Right bundle branch block with normal, left or right axis deviation. Am J Med 51:432, 1971 Strauss S, Langendorf R: Bilateral partial bundle branch block. Am J Sci 205:233, 1943 Unger PN, Lesser ME, Kugel VH, et al: Concept of "masquerading" bundle branch block: An electrocardiographic pathological correlation. Circulation 17 :397, 1958 Daroff RB, Solitare GB, Pincus JH, et al: Spongiform encephalopathy with chronic progressive external ophthalmoplegia. Neurology 16: 161, 1966 Narula OS, Scherlag BJ, Samet P, et al: Atrioventricular block : Localization and classification by His bundle recordings. Am J Med 50: 146, 1971 Barold SS, Friedberg DH: Second degree atrioventricular block. Am J Cardiol 33 :311, 1974 Scherlag BJ, Lau SH, Helfant RH, et al: Catheter technique for recording His bundle activity in man. Circulation 39:13, 1969

730 MAHAJAN, KUPFERER, VAN ORDSTRAND

Pneumothorax* A Rare Manifestation of Primary Lung Cancer Vi;ay Maha;an, M.D.; Carl F. Kupferer, D.O.; and HowardS. Van Ordstrand, M.D., F .C C . .P.

Spontaneous pneumothorax rarely occurs with primary lung cancer. A case of giant cell carcinoma of the lung is reported, in which pneumothorax was the presenting feature. The rarity of this association is stressed. A limited review of the English literature Is included.

P

neumothorax is a rare manifestation of bronchogenic carcinoma. Few cases have been reported in the literature. We are reporting a case of primary giant cell carcinoma of the lung in which spontaneous pneumothorax was the presenting feature.

CASE

REPoRT

This 39-year-old black man, a cosmetologist, was in good health until six weeks prior to his admission to the Cleveland Clinic Hospital. He reported to the emergency room because of the onset of acute severe pain localized to the anterior and lateral aspects of the lower right hemithorax. This pain had awakened him from sleep and increased in severity with respiratory excursions. Further questioning revealed that he had experienced increasing effort dyspnea, a dry nonproductive cough, and a 9.5-kg ( 20.9-lb) weight loss during the preceding six weeks. The patient had also noted a low-grade intermittent fever for the past three weeks. There was no history of hemoptysis, orthopnea, paroxysmal nocturnal dyspnea, or any chest pain prior to this present episode. He had a 20-year history of smoking but had stopped with the onset of his illness. The physical examination revealed that the patient was pale and tachypneic. There was early clubbing of the fingers . Examination of the chest showed a diminished percussion note in the right infrascapular and mammary areas and increased resonance at the right apex. Breath sounds were diminished over the entire right hemithorax, and a pleural friction rub was audible in the right infrascapular area. Examination of the other systems revealed no significant abnormality. The chest roentgenogram (Fig I) revealed a large 18-cm mass occupying the lower three-fourths of the right hemithorax. Increased translucency due to pneumothorax was noted at the right base and apex. The left lung appeared normal. There was no mediastinal shift. Laboratory studies at the time of admission revealed significant anemia, leukocytosis, slight hypoxemia, hypocapnia, and respiratory alkalosis. A clinical diagnosis of probable bronchogenic carcinoma of the right lung with spontaneous pneumothorax was made. A transthoracic aspiration needle biopsy was performed under image-intensification fluoroscopy. The material obtained was noted to be necrotic, and the cytologic findings were suggestive of malignancy. The results of sputum examination for aerobic and anaerobic bacteria, acid-fast bacilli, and fungi •From the Department of Pulmonary Disease, the Cleveland Clinic Foundation and the Cleveland Clinic Educational Foundation, Cleveland. Reprint requests.: Dr. Mahafan, Cleveland Clinic Foundation, Cleveland 44106

CHEST, 68: 5, NOVEMBER, 1975