Cardiac Involvement in the Kugelberg-Welander
HIROMITSU TANAKA, NOBUHIRO UEMURA, YOSHIFUMI TOYAMA, AK10 KUDO, MD YOHSUKE OHKATSU, TAKUYA KANEHISA,
MD MD MD MD* MD
From the First Department and the Third Department of Internal Medicine, Faculty of Medicine, Kagoshima University, Kagoshima, Japan. This study was supported in part by a research grant for cardiomyopathy from the Ministry of Health and Welfare, Tokyo, Japan. Manuscript received December 4, 1975; revised manuscript received April 7, 1976, accepted April 14, 1976. Address for reprints: Hiromitsu Tanaka, MD, The First Department of Internal Medicine, Faculty of Medicine, Kagoshima University, Kagoshima, 890, Japan.
528
October 1978
Syndrome
Two cases of the Kugelberg-Welander syndrome (juvenile form of progressive spinal muscular atrophy) associated with cardiomyopathy and cardiomegaly are presented. The first patient, a 24 year old man, had atrial flutter with complete atrioventricular (A-V) block due to A-H block. Echocardiography revealed an increase in the left atrial and right ventricular dimensions. The second patient was a 26 year old man whose electrocardiogram revealed an A-V junctional rhythm, deep Q wave in leads I, aVL and Vs to Vs and an RS pattern in lead VI. Histologic examination of the myocardium in Case 2 showed slight interstitial fibrosis. Review of previously reported cases shows that (1) the atrium, the ventricular myocardium and A-V conducting tissue may be involved, and (2) atrial arrhythmias, A-V conduction disturbances and congestive heart failure may occur in the Kugelberg-Welander syndrome.
Among heredofamilial degenerative neuromuscular diseases, Friedreich’s ataxia,’ myotonic dystrophy2a3 and Duchenne’s muscular dystrophy4*5 are very often associated with cardiomyopathy. The heart has also been reported to be involved in other neuromuscular diseases including the Roussy-Levy syndrome,6 familial spastic paraplegia,7 the cerebellar form of spinocerebellar degenerations peroneal muscular atrophy,g spinal scapuloperoneal muscular atrophy, lo limb-girdle muscular dystrophy,5 facioscapulohumeral muscular dystrophy,5 distal myopathy,ll ocular myopathy12 and scapuloperoneal dystrophy.13 Study of the cardiomyopathy associated with these diseases is of importance, not only from the standpoint of clinical practice but also from the standpoint of contributing to the etiology of idiopathic cardiomyopathy, especially regarding genetic factors in the development of familial cardiomyopathy. The Kugelberg-Welander syndrome is a juvenile form of progressive spinal muscular atrophy described by Wohlfart et a1.14 and Kugelberg and Welander.15 The characteristic features are (1) onset in childhood or adolescence, (2) atrophy and weakness of proximal limb muscles followed by involvement of distal muscles, (3) slowly progressive clinical course, (4) occurrence of fasciculation and electromyographic and muscle biopsy evidence of lower motor neuron lesion, and (5) nonsex-linked recessive mode of inheritance. There have been only a few case reports of cardiac changes in this syndrome. In this paper, we present two cases of Kugelberg-Welander syndrome with cardiac involvement. Methods of Cardiovascular
Examination
His bundle electrography: His bundle electrograms were recorded by the method of Scherlag et a1.16using a no. 6 tripolar probe (Castillo) and a multichannel recorder (rectigraph and visigraph, Sanei Sokki Co., Ltd.) with the frequency response set at 500 hertz and the time constant at 0.003 second. The paper speed was either 100 or 125 mm/set. Atria1 pacing was performed with a second catheter positioned against the lateral wall of the right atrium, using
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CARDIAC INVOLVEMENT IN KUGELBERG-WELANDER SYNDROME-TANAKA
a Medtronic 5880 A pacemaker. The P-A, A-H and H-V intervals were measured according to the method of Narula et al.” Echocardiography: Echocardiograms were obtained using a sonolayergraph model SSL-51 H (Toshiba Co., Ltd.) and a 2.0 megahertz transducer with a diameter of 1 cm. They were recorded on a strip chart recorder (model OR-OlA, Toshiba Co., Ltd.). Right ventricular dimension, left ventricular internal dimension, left ventricular and interventricular septal wall thicknesses, left atria1 dimension, aortic root and E-F slope and amplitude of the anterior mitral valve leaflet were measured according to the method of Feigenbaum.18 Endomyocardial biopsy: Myocardial biopsy was performed using a Konno-Sakakibara endomyocardial bioptome.lg Histologic sections of the biopsy specimens were stained with hematoxylin-eosin.
Case 1
Presentation
of Cases
A 24 year old tailor was admitted to Kagoshima University Hospital because of arrhythmias in October 1974. He seemed normal until age 6 years, when it was noted that he was clumsy in running. Proximal weakness of the arms was noted several years before admission. He was found to have bradycardia at age 19 years but he did not experience syncope or palpitation. Several weeks before his admission, precordial distress developed. One uncle and one cousin were reported to be affected by neurologic disorders.
ET AL.
On admission, he was well developed. The pulse was 44/min and regular. The blood pressure was 120/60 mm Hg. A grade 2/6 systolic murmur was heard at the cardiac base. A soft and smooth liver was palpable 3 cm below the right costal margin. The spleen was not palpable. Neurologic examination disclosed muscular weakness and atrophy in the proximal portion of the arms and both proximal and distal portions of the legs. Fasciculations were seen. Only the Achilles tendon reflexes were elicited. The gait was waddling. The sensory examination was normal. Pes cavus was noted. The electromyogram showed a neurogenic pattern. Muscle biopsy revealed neurogenie muscular atrophy. The nerve conduction velocity was 60 m/set in the left ulnar nerve. The serum glutamic oxaloacetic transaminase (SGOT) was 108 units, glutamic pyruvic transaminase (SGPT) was 156 units and creatine phosphokinase (CPK) ranged from 57.5 to 84 units (normal less than 35 units). Measurements of serum cholesterol, beta lipoprotein, triglycerides, electrolytes, protein fractions and blood glucose were all within normal range. The chest X-ray film revealed moderate cardiomegaly with normal lung fields. The electrocardiogram on admission (Fig. 1) revealed atria1 flutter with complete atrioventricular (A-V) block. A His bundle electrogram (Fig. 2) showed a sharp and diphasic His bundle potential (H) preceding each V wave. The H-V interval was 50 msec. No A wave was followed by a His bundle potential. The rate of V waves was 40fmin. Thus it was demonstrated that the A-V block was due to A-H block.17 An
FIGURE 1. Case 1. Electrocardiogram showing atrial flutter with complete A-V block. The R-R intervals are almost regular and measure 1.4 seconds.
/
.a
FIGURE 2. Case 1. His bundle electrogram and electrocardiogram (lead II) showing atrial flutter with complete A-V block due to A-H block. The His bundle potential is recorded before each V wave. The H-V interval is 50 msec.
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FIGURE 3. Case 1. Echocardiograms. Left, an undulatorypattern synchronous with the flutter waves in the electrocardiogram is present in the anterior (AMV) and posterior (PMV) mitral valve leaflets and interventricular septum (IVS). Right, tricuspid valve echoes (TV) show the same pattern.
echocardiogram (Fig. 3) showed an undulatory pattern of mitral valve leaflets, tricuspid valve leaflets and interventricular septum. Right ventricular and left atria1 dimensions (1.4 and 2.3 cm/m2, respectively) were increased. The electrocardiogram taken several weeks later revealed sinus bradycardia with complete A-V block. Right heart catheterization revealed normal intracardiac pressures and no intracardiac shunt.
Case 2 A 26 year old man was admitted for further evaluation of heart disease in July 1973. He had had difficulty in running since childhood. At age 16 years he noticed proximal muscular atrophy of the limbs and since then had had slowly progressive difficulty in walking. Three months before admission, he was
told that he had cardiomegaly and an abnormal electrocardiogram. He complained of exertional palpitation. An uncle and a cousin were reported to have similar abnormality of the musculature. On admission, he was moderately developed and well nourished. The pulse was 84/min and regular. The blood pressure was 132/84 mm Hg. On auscultation, a grade 2/6 systolic murmur at the apex and a grade l/6 systolic murmur at the base were audible. Muscular atrophy and weakness of the proximal type were noted. The deep tendon reflexes were normal or slightly diminished. The gait was waddling. The sensation was normal. The electromyogram revealed a mixed neurogenic and myogenic pattern. Muscle biopsy of the right quadriceps femoris muscle revealed mixed neurogenic and myogenic muscular atrophy. The serum electrolytes, SGOT, SGPT, serum protein fraction and serum cholesterol were all within normal range. The serum CPK ranged from 49.2 to 156.5 units. Serologic tests for syphilis were negative. The chest X-ray film (Fig. 4) showed cardiomegaly. The electrocardiogram (Fig. 5) revealed an A-V junctional rhythm. The mean QRS axis was about 0’. There were deep Q waves in leads I, aVL and V5 to Vs, and an RS in VI. Small notches in the QRS complex were seen in leads II, III, aVL and aVF. His bundle electrograms showed normal values; the P-A interval was 30 msec, the A-H interval 56 msec and the H-V interval 40 msec. The A-V conducting response to atrial pacing was also normal.20 Right heart catheterization revealed no abnormality. A biopsy specimen obtained from the right ventricle showed a slight interstitial fibrosis.
Discussion
FIGURE 4. Case 2. Chest X-ray film showing cardiomegaly. The cardiothoracic ratio is 0.587.
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Cardiac involvement: There have been only a few reports of the cardiac changes in the KugelbergWelander syndrome (Table I). In 1971, Sterz et a1.21 described two brothers with the Kugelberg-Welander syndrome who had atrial fibrillation. The older brother, aged 35 years, manifested Adams-Stokes syndrome, atria1 fibrillation and A-V block with idioventricular rhythm; he was successfully treated with implantation of an artificial cardiac pacemaker. The younger brother
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had atria1 fibrillation and cardiomegaly. Descriptions of three patients with Kugelberg-Welander disease and cardiomyopathy have appeared in Japanese. Matsumoto et a1.22 described a 23 year old man with this disease in 1971. The patient had cardiomegaly, ascites, hepatomegaly and edema. The electrocardiogram revealed atria1 standstill and low voltage of the QRS complexes. Sugimura et a1.23 described two other patients with this disease. The first was a 23 year old woman who complained of exertional palpitation. The electrocardiogram revealed first degree A-V block, atrial premature beats and paroxysmal atrial tachycardia. His bundle electrograms revealed prolongation of the A-H interval. Fibrosis of the right atrium was demonstrated
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ET AL.
by endomyocardial biopsy. The second patient, a 31 year old man, had dyspnea. The electrocardiogram showed transient atria1 fibrillation, atria1 premature beats, left axis deviation and T waves suggesting coronary disease. Patient 1 in our study had precordial distress, cardiomegaly and atria1 flutter with complete A-V block due to A-H block; Patient 2 had exertional dyspnea, cardiomegaly, A-V junctional rhythm and abnormal Q waves. Thus, among seven patients with symptomatic heart disease, atria1 arrhythmias were found in six, cardiac conduction disturbances in four, cardiomegaly in five and frank heart failure in two. The atria1 arrhythmias frequently found in patients with the Kugelberg-Welander syndrome may indicate
FIGURE 5. Case 2. Electrocardiogram showing A-V junctional rhythm with abnormal Q waves and QRS notching.
TABLE Reported case “0.
I Cases of the Kugelberg-Welander
Syndrome
with Symptomatic
Cardiomyopathy
Age (vr) Reference
& sex
Cardiac Symptoms
1
Sterz et al?’
35M
Exertional dyspnea, Adams-Stokes syndrome
2 3
Sterz et al.” Matsumoto et al.232
29M 23M
Cardiomegaly Cardiomegaly, ascites, hepatomegaly, edema
4
Sugimura
et al.23
23F
Exertional
palpitation
5
Sugimura
et al.*s
31M
Dyspnea,
cardiomegaly
6
Present report
24M
7
Present report
26M
Precordial distress, cardiomegaly Exertional palpitation, cardiomegaly
ECG A Fib, A-V block with idioventricular rhythm, implanted cardiac pacemaker A Fib Atrial standstill with A-V nodal rhythm, low voltage of QRS SVPB, 1” A-V block, PAT, A-V nodal rhythm A Fib, APB, left axis deviation, coronary type T wave, slurred R AF, complete A-V block Deep Q in leads I, aVL, V, to V,, notched QRS, RS in V,
HBE
Biopsy
-
-
-
-
A-H block -
A-H block Normal
Fibrosis of RA; normal RV -
Fibrosis of RV
AF = atrial flutter; A Fib = atrial fibrillation; APB = atrial premature beats; A-V = atrioventricular; ECG = electrocardiogram; HBE = His bundle electrogram: LVH = left ventricular hypertrophy; PAT = paroxysmal atrial tachycardia; RA = right atrium; RV = right ventricle; SVPB = supraventricular premature beats.
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the presence of atrial disease because right atrial fibrosis was demonstrated in a patient who had this disease and atria1 arrhythmias (Sugimura’s Case 1)23 and because atria1 standstill was observed in another patient (Matsumoto’s case).22 Conduction disturbances (particularly advanced A-V block, found in two patients (Sterz’s case21 and Case 2 in our study) suggest the presence of organic lesions in the A-V conducting system in this syndrome. Cardiomegaly, frank heart failure and the pathologic changes in the right ventricle demonstrated in our study indicate that the ventricular myocardium also may be involved. We also observed some degenerated myocytes showing preferential loss of myosin filaments24 in the myocardium from a patient with Kugelberg-Welander. syndrome (unpublished data). Therefore, the atrium, the A-V conducting system and the ventricular muscle may be involved together, although atrial arrhythmias are the most frequent clinical findings. Echocardiogram: Echocardiographic findings in the Kugelberg-Welander syndrome have not previously been reported. Both the right ventricular and left atria1 dimensions were increased m Case 1, suggesting right ventricular and left atria1 enlargement. An undulatory pattern of both mitral valve leaflets, both tricuspid valve leaflets and interventricular septum occurred during atria1 flutter with A-V block. The pattern is caused by
ET AL.
atrial flutter.25 To our knowledge, this is the first report of such a pattern in the tricuspid valve. Neurogenic and myopathic changes: From studies of muscle biopsy specimens, electromyograms and blood chemistry data, both neurogenic and myopathic changes have been found in the skeletal muscle in this syndrome.2s-“8 However, it is controversial whether the primary site of the lesion is the anterior horn cells or both the anterior horn cells and the skeletal muscle itself.262s It remains to be determined whether the lesion of the anterior horn cells, with or without dystrophic changes in skeletal muscle, is related to that of atrial and ventricular working myocardium and the A-V conduction system of patients with the Kugelberg-Welander syndrome. It seems necessary from the practical and etiologic standpoints that more attention be drawn to the cardiac changes in the heredofamilial degenerative diseases, including those in which the association with cardiomyopathy is thought to be uncommon. Acknowledgment We gratefully acknowledge the critical review of the manuscript by Dr. V. J. Ferrans, Section of Pathology, National Institute of Health. We also thank Dr. A. Igata, Director of the Third Department of Internal Medicine, Faculty of Medicine, Kagoshima University and Dr. S. Terashi, the First Department of Pathology, Faculty of Medicine, Kagoshima University, for their advice.
References 1. Thoren C: Cardiomyopathy in Friedreich’s ataxia. With studies of cardiovascular and respiratory function. Acta Paediatr Stand [Suppl] 153:1-131, 1964 2. Church SC: The heart in myotonia atrophica. Arch Intern Med 119:176-181, 1967 3. Uemura N, Tanaka H, Niimura T, et al: Electrophysiological and histological abnormalities of the heart in myotonic dystrophy. Am Heart J 86:616-624, 1973 4. Gilroy J, Cahalm JL, Berman R, et al: Cardiac and pulmonary complications in Duchenne’s progressive muscular dystrophy. Circulation 27:484-493, 1963 5. Perloff JK, de Leon AC, O’Doherty D: The cardiomyopathy of progressive muscular dystrophy. Circulation 33:625-648, 1966 6. Lascelles RG, Barker IA, Thomas PK: Hereditary polyneuropathy of Roussy-Levy type with associated cardiomyopathy. Guy’s Hosp Rep 119:253-262, 1970 7. Sutterland JM: Familial spastic paraplegia. Its relation to mental and cardiac abnormalities. Lancet 2:169-l 70, 1957 8. Tanaka H, Niimura T, Kashima T, et al: Cardiomyopathy with hereditary cerebellar ataxia. Report of an autopsied case. Jpn Heart J 13:369-377, 1972 9. Littler WA: Heart block and peroneal muscular atrophy. A family study. Q J Med 39:431-439, 1970 10. Mawatari S, Katayama K: Scapuloperoneal muscular atrophy with cardiopathy. An X-linked recessive trait. Arch Neurol 28:55-59, 1973 11. Markesberg WI?, Griggs RC, Leach RP, et al: Late onset hereditary distal myopathy. Neurology (Minneap) 24:127-134, 1974 12. Uppal SC: Kearns’ syndrome, a new form of cardiomyopathy. Br Heart J 351766-769, 1973 13. Takahashi T, Nakamura H, Nakashima R: Scapuloperoneal dystrophy associated with neurogenic changes. J Neurol Sci 23: 575-583, 1974 14. Wohlfarl G, Fex J, Eliassert S: Hereditary proximal spinal muscular atrophy: a clinical entity simulating progressive muscular dystrophy. Acta Psychiatr Neurol Stand 30:395-406, 1955 15. Kugelberg E, Welander L: Heredofamilial juvenile muscular atrophy simulating muscular dystrophy. Arch Neurol Psychiatr 75:500-509, 1956
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16. Scherlag BJ, Lau SH, Helfant RH, et al: Catheter technique for recording of His bundle activity in man. Circulation 39:13-18, 1969 17. Narula OS, Scherlag BJ, Samet P, et al: Atrioventricular block. Localization and classification by His bundle recordings. Am J Med 50:146-165, 1971 18. Feigenbaum H: Echocardiography. Philadelphia, Lea & Febiger, 1973, p 216 19. Konno S, Sakakibara S: Endomyocardial biopsy. Dis Chest 44: 345-350, 1963 20. Rosen KM: The contribution of His bundle recording to the understanding of cardiac conduction in man. Circulation 43:961-966, 1971 21. Sterz H, Harrer G, Marchet HP, et al: Primare und neurogene Skeletmuskelerkrankungen bzw.-paralysen mit schweren kardialen Rhythmstbrungen. Z Kreislaufforsch 60: l- 13, 197 1 22. Matsumoto K, Kakiuchi F, Kaklhana M, et al: Kugelberg-Welander disease with cardiopathy of unknown etiology. Clinical report of a case. Respiration and Circulation 19:863-870, 1971 (in Japanese with English abstract) 23. Sugimura F, lijima M, Ozawa Y, et al: Two cases of KugelbergWelander’s disease with cardiopathy. Clin Neurol (Tokyo) 13: 79-86, 1973 (in Japanese with English abstract) 24. Maron BJ, Ferrans VC, Roberts WC: Ultrastructural features of degenerated cardiac muscle cells in patients with cardiac hypertrophy. Am J Pathol 79:387-434, 1975 25. Zoneraich S, Zoneraich 0, Rhee JJ: Echocardiographic findings in atrial flutter. Circulation 52:455-459, 1975 26. Hausmanowa-Petrusewicz I, Askanas W, Badurska B, et al: Infantile and juvenile spinal muscular atrophy. J Neurol Sci 6: 269-287, 1968 27. Kondo K: Beitrag zur “pseudodystrophischen” Natur der Amyotrophie bei der Wohlfart-Kugelberg-Welanderschen Krankheit. Acta Neuropathol (Berl) 13:29-42, 1969 28. Mastaglia FL, Walton JN: Histological and histochemical changes in skeletal muscle from cases of chronic juvenile and early adult spinal muscular atrophy (the Kugelberg-Welander syndrome). J Neurol Sci 12:15-44, 1971
Volume 39
HIROMITSU TANAKA, NOBUHIRO UEMURA, YOSHIFUMI TOYAMA, AK10 KUDO, MD YOHSUKE OHKATSU, TAKUYA KANEHISA,
MD MD MD MD* MD
From the First Department and the Third Department of Internal Medicine, Faculty of Medicine, Kagoshima University, Kagoshima, Japan. This study was supported in part by a research grant for cardiomyopathy from the Ministry of Health and Welfare, Tokyo, Japan. Manuscript received December 4, 1975; revised manuscript received April 7, 1976, accepted April 14, 1976. Address for reprints: Hiromitsu Tanaka, MD, The First Department of Internal Medicine, Faculty of Medicine, Kagoshima University, Kagoshima, 890, Japan.
528
October 1978
Syndrome
Two cases of the Kugelberg-Welander syndrome (juvenile form of progressive spinal muscular atrophy) associated with cardiomyopathy and cardiomegaly are presented. The first patient, a 24 year old man, had atrial flutter with complete atrioventricular (A-V) block due to A-H block. Echocardiography revealed an increase in the left atrial and right ventricular dimensions. The second patient was a 26 year old man whose electrocardiogram revealed an A-V junctional rhythm, deep Q wave in leads I, aVL and Vs to Vs and an RS pattern in lead VI. Histologic examination of the myocardium in Case 2 showed slight interstitial fibrosis. Review of previously reported cases shows that (1) the atrium, the ventricular myocardium and A-V conducting tissue may be involved, and (2) atrial arrhythmias, A-V conduction disturbances and congestive heart failure may occur in the Kugelberg-Welander syndrome.
Among heredofamilial degenerative neuromuscular diseases, Friedreich’s ataxia,’ myotonic dystrophy2a3 and Duchenne’s muscular dystrophy4*5 are very often associated with cardiomyopathy. The heart has also been reported to be involved in other neuromuscular diseases including the Roussy-Levy syndrome,6 familial spastic paraplegia,7 the cerebellar form of spinocerebellar degenerations peroneal muscular atrophy,g spinal scapuloperoneal muscular atrophy, lo limb-girdle muscular dystrophy,5 facioscapulohumeral muscular dystrophy,5 distal myopathy,ll ocular myopathy12 and scapuloperoneal dystrophy.13 Study of the cardiomyopathy associated with these diseases is of importance, not only from the standpoint of clinical practice but also from the standpoint of contributing to the etiology of idiopathic cardiomyopathy, especially regarding genetic factors in the development of familial cardiomyopathy. The Kugelberg-Welander syndrome is a juvenile form of progressive spinal muscular atrophy described by Wohlfart et a1.14 and Kugelberg and Welander.15 The characteristic features are (1) onset in childhood or adolescence, (2) atrophy and weakness of proximal limb muscles followed by involvement of distal muscles, (3) slowly progressive clinical course, (4) occurrence of fasciculation and electromyographic and muscle biopsy evidence of lower motor neuron lesion, and (5) nonsex-linked recessive mode of inheritance. There have been only a few case reports of cardiac changes in this syndrome. In this paper, we present two cases of Kugelberg-Welander syndrome with cardiac involvement. Methods of Cardiovascular
Examination
His bundle electrography: His bundle electrograms were recorded by the method of Scherlag et a1.16using a no. 6 tripolar probe (Castillo) and a multichannel recorder (rectigraph and visigraph, Sanei Sokki Co., Ltd.) with the frequency response set at 500 hertz and the time constant at 0.003 second. The paper speed was either 100 or 125 mm/set. Atria1 pacing was performed with a second catheter positioned against the lateral wall of the right atrium, using
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CARDIAC INVOLVEMENT IN KUGELBERG-WELANDER SYNDROME-TANAKA
a Medtronic 5880 A pacemaker. The P-A, A-H and H-V intervals were measured according to the method of Narula et al.” Echocardiography: Echocardiograms were obtained using a sonolayergraph model SSL-51 H (Toshiba Co., Ltd.) and a 2.0 megahertz transducer with a diameter of 1 cm. They were recorded on a strip chart recorder (model OR-OlA, Toshiba Co., Ltd.). Right ventricular dimension, left ventricular internal dimension, left ventricular and interventricular septal wall thicknesses, left atria1 dimension, aortic root and E-F slope and amplitude of the anterior mitral valve leaflet were measured according to the method of Feigenbaum.18 Endomyocardial biopsy: Myocardial biopsy was performed using a Konno-Sakakibara endomyocardial bioptome.lg Histologic sections of the biopsy specimens were stained with hematoxylin-eosin.
Case 1
Presentation
of Cases
A 24 year old tailor was admitted to Kagoshima University Hospital because of arrhythmias in October 1974. He seemed normal until age 6 years, when it was noted that he was clumsy in running. Proximal weakness of the arms was noted several years before admission. He was found to have bradycardia at age 19 years but he did not experience syncope or palpitation. Several weeks before his admission, precordial distress developed. One uncle and one cousin were reported to be affected by neurologic disorders.
ET AL.
On admission, he was well developed. The pulse was 44/min and regular. The blood pressure was 120/60 mm Hg. A grade 2/6 systolic murmur was heard at the cardiac base. A soft and smooth liver was palpable 3 cm below the right costal margin. The spleen was not palpable. Neurologic examination disclosed muscular weakness and atrophy in the proximal portion of the arms and both proximal and distal portions of the legs. Fasciculations were seen. Only the Achilles tendon reflexes were elicited. The gait was waddling. The sensory examination was normal. Pes cavus was noted. The electromyogram showed a neurogenic pattern. Muscle biopsy revealed neurogenie muscular atrophy. The nerve conduction velocity was 60 m/set in the left ulnar nerve. The serum glutamic oxaloacetic transaminase (SGOT) was 108 units, glutamic pyruvic transaminase (SGPT) was 156 units and creatine phosphokinase (CPK) ranged from 57.5 to 84 units (normal less than 35 units). Measurements of serum cholesterol, beta lipoprotein, triglycerides, electrolytes, protein fractions and blood glucose were all within normal range. The chest X-ray film revealed moderate cardiomegaly with normal lung fields. The electrocardiogram on admission (Fig. 1) revealed atria1 flutter with complete atrioventricular (A-V) block. A His bundle electrogram (Fig. 2) showed a sharp and diphasic His bundle potential (H) preceding each V wave. The H-V interval was 50 msec. No A wave was followed by a His bundle potential. The rate of V waves was 40fmin. Thus it was demonstrated that the A-V block was due to A-H block.17 An
FIGURE 1. Case 1. Electrocardiogram showing atrial flutter with complete A-V block. The R-R intervals are almost regular and measure 1.4 seconds.
/
.a
FIGURE 2. Case 1. His bundle electrogram and electrocardiogram (lead II) showing atrial flutter with complete A-V block due to A-H block. The His bundle potential is recorded before each V wave. The H-V interval is 50 msec.
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FIGURE 3. Case 1. Echocardiograms. Left, an undulatorypattern synchronous with the flutter waves in the electrocardiogram is present in the anterior (AMV) and posterior (PMV) mitral valve leaflets and interventricular septum (IVS). Right, tricuspid valve echoes (TV) show the same pattern.
echocardiogram (Fig. 3) showed an undulatory pattern of mitral valve leaflets, tricuspid valve leaflets and interventricular septum. Right ventricular and left atria1 dimensions (1.4 and 2.3 cm/m2, respectively) were increased. The electrocardiogram taken several weeks later revealed sinus bradycardia with complete A-V block. Right heart catheterization revealed normal intracardiac pressures and no intracardiac shunt.
Case 2 A 26 year old man was admitted for further evaluation of heart disease in July 1973. He had had difficulty in running since childhood. At age 16 years he noticed proximal muscular atrophy of the limbs and since then had had slowly progressive difficulty in walking. Three months before admission, he was
told that he had cardiomegaly and an abnormal electrocardiogram. He complained of exertional palpitation. An uncle and a cousin were reported to have similar abnormality of the musculature. On admission, he was moderately developed and well nourished. The pulse was 84/min and regular. The blood pressure was 132/84 mm Hg. On auscultation, a grade 2/6 systolic murmur at the apex and a grade l/6 systolic murmur at the base were audible. Muscular atrophy and weakness of the proximal type were noted. The deep tendon reflexes were normal or slightly diminished. The gait was waddling. The sensation was normal. The electromyogram revealed a mixed neurogenic and myogenic pattern. Muscle biopsy of the right quadriceps femoris muscle revealed mixed neurogenic and myogenic muscular atrophy. The serum electrolytes, SGOT, SGPT, serum protein fraction and serum cholesterol were all within normal range. The serum CPK ranged from 49.2 to 156.5 units. Serologic tests for syphilis were negative. The chest X-ray film (Fig. 4) showed cardiomegaly. The electrocardiogram (Fig. 5) revealed an A-V junctional rhythm. The mean QRS axis was about 0’. There were deep Q waves in leads I, aVL and V5 to Vs, and an RS in VI. Small notches in the QRS complex were seen in leads II, III, aVL and aVF. His bundle electrograms showed normal values; the P-A interval was 30 msec, the A-H interval 56 msec and the H-V interval 40 msec. The A-V conducting response to atrial pacing was also normal.20 Right heart catheterization revealed no abnormality. A biopsy specimen obtained from the right ventricle showed a slight interstitial fibrosis.
Discussion
FIGURE 4. Case 2. Chest X-ray film showing cardiomegaly. The cardiothoracic ratio is 0.587.
530
October 1976
The American Journal of CARDIOLOGY
Cardiac involvement: There have been only a few reports of the cardiac changes in the KugelbergWelander syndrome (Table I). In 1971, Sterz et a1.21 described two brothers with the Kugelberg-Welander syndrome who had atrial fibrillation. The older brother, aged 35 years, manifested Adams-Stokes syndrome, atria1 fibrillation and A-V block with idioventricular rhythm; he was successfully treated with implantation of an artificial cardiac pacemaker. The younger brother
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CARDIAC INVOLVEMENT
had atria1 fibrillation and cardiomegaly. Descriptions of three patients with Kugelberg-Welander disease and cardiomyopathy have appeared in Japanese. Matsumoto et a1.22 described a 23 year old man with this disease in 1971. The patient had cardiomegaly, ascites, hepatomegaly and edema. The electrocardiogram revealed atria1 standstill and low voltage of the QRS complexes. Sugimura et a1.23 described two other patients with this disease. The first was a 23 year old woman who complained of exertional palpitation. The electrocardiogram revealed first degree A-V block, atrial premature beats and paroxysmal atrial tachycardia. His bundle electrograms revealed prolongation of the A-H interval. Fibrosis of the right atrium was demonstrated
IN KUGELBERGWELANDER
SYNDROME-TANAKA
ET AL.
by endomyocardial biopsy. The second patient, a 31 year old man, had dyspnea. The electrocardiogram showed transient atria1 fibrillation, atria1 premature beats, left axis deviation and T waves suggesting coronary disease. Patient 1 in our study had precordial distress, cardiomegaly and atria1 flutter with complete A-V block due to A-H block; Patient 2 had exertional dyspnea, cardiomegaly, A-V junctional rhythm and abnormal Q waves. Thus, among seven patients with symptomatic heart disease, atria1 arrhythmias were found in six, cardiac conduction disturbances in four, cardiomegaly in five and frank heart failure in two. The atria1 arrhythmias frequently found in patients with the Kugelberg-Welander syndrome may indicate
FIGURE 5. Case 2. Electrocardiogram showing A-V junctional rhythm with abnormal Q waves and QRS notching.
TABLE Reported case “0.
I Cases of the Kugelberg-Welander
Syndrome
with Symptomatic
Cardiomyopathy
Age (vr) Reference
& sex
Cardiac Symptoms
1
Sterz et al?’
35M
Exertional dyspnea, Adams-Stokes syndrome
2 3
Sterz et al.” Matsumoto et al.232
29M 23M
Cardiomegaly Cardiomegaly, ascites, hepatomegaly, edema
4
Sugimura
et al.23
23F
Exertional
palpitation
5
Sugimura
et al.*s
31M
Dyspnea,
cardiomegaly
6
Present report
24M
7
Present report
26M
Precordial distress, cardiomegaly Exertional palpitation, cardiomegaly
ECG A Fib, A-V block with idioventricular rhythm, implanted cardiac pacemaker A Fib Atrial standstill with A-V nodal rhythm, low voltage of QRS SVPB, 1” A-V block, PAT, A-V nodal rhythm A Fib, APB, left axis deviation, coronary type T wave, slurred R AF, complete A-V block Deep Q in leads I, aVL, V, to V,, notched QRS, RS in V,
HBE
Biopsy
-
-
-
-
A-H block -
A-H block Normal
Fibrosis of RA; normal RV -
Fibrosis of RV
AF = atrial flutter; A Fib = atrial fibrillation; APB = atrial premature beats; A-V = atrioventricular; ECG = electrocardiogram; HBE = His bundle electrogram: LVH = left ventricular hypertrophy; PAT = paroxysmal atrial tachycardia; RA = right atrium; RV = right ventricle; SVPB = supraventricular premature beats.
October 1976
The American Journal of CARDIOLOGY
Volume 36
531
CARDIAC
INVOLVEMENT
IN KUGELBERG-WELANDER
SYNDROME-TANAKA
the presence of atrial disease because right atrial fibrosis was demonstrated in a patient who had this disease and atria1 arrhythmias (Sugimura’s Case 1)23 and because atria1 standstill was observed in another patient (Matsumoto’s case).22 Conduction disturbances (particularly advanced A-V block, found in two patients (Sterz’s case21 and Case 2 in our study) suggest the presence of organic lesions in the A-V conducting system in this syndrome. Cardiomegaly, frank heart failure and the pathologic changes in the right ventricle demonstrated in our study indicate that the ventricular myocardium also may be involved. We also observed some degenerated myocytes showing preferential loss of myosin filaments24 in the myocardium from a patient with Kugelberg-Welander. syndrome (unpublished data). Therefore, the atrium, the A-V conducting system and the ventricular muscle may be involved together, although atrial arrhythmias are the most frequent clinical findings. Echocardiogram: Echocardiographic findings in the Kugelberg-Welander syndrome have not previously been reported. Both the right ventricular and left atria1 dimensions were increased m Case 1, suggesting right ventricular and left atria1 enlargement. An undulatory pattern of both mitral valve leaflets, both tricuspid valve leaflets and interventricular septum occurred during atria1 flutter with A-V block. The pattern is caused by
ET AL.
atrial flutter.25 To our knowledge, this is the first report of such a pattern in the tricuspid valve. Neurogenic and myopathic changes: From studies of muscle biopsy specimens, electromyograms and blood chemistry data, both neurogenic and myopathic changes have been found in the skeletal muscle in this syndrome.2s-“8 However, it is controversial whether the primary site of the lesion is the anterior horn cells or both the anterior horn cells and the skeletal muscle itself.262s It remains to be determined whether the lesion of the anterior horn cells, with or without dystrophic changes in skeletal muscle, is related to that of atrial and ventricular working myocardium and the A-V conduction system of patients with the Kugelberg-Welander syndrome. It seems necessary from the practical and etiologic standpoints that more attention be drawn to the cardiac changes in the heredofamilial degenerative diseases, including those in which the association with cardiomyopathy is thought to be uncommon. Acknowledgment We gratefully acknowledge the critical review of the manuscript by Dr. V. J. Ferrans, Section of Pathology, National Institute of Health. We also thank Dr. A. Igata, Director of the Third Department of Internal Medicine, Faculty of Medicine, Kagoshima University and Dr. S. Terashi, the First Department of Pathology, Faculty of Medicine, Kagoshima University, for their advice.
References 1. Thoren C: Cardiomyopathy in Friedreich’s ataxia. With studies of cardiovascular and respiratory function. Acta Paediatr Stand [Suppl] 153:1-131, 1964 2. Church SC: The heart in myotonia atrophica. Arch Intern Med 119:176-181, 1967 3. Uemura N, Tanaka H, Niimura T, et al: Electrophysiological and histological abnormalities of the heart in myotonic dystrophy. Am Heart J 86:616-624, 1973 4. Gilroy J, Cahalm JL, Berman R, et al: Cardiac and pulmonary complications in Duchenne’s progressive muscular dystrophy. Circulation 27:484-493, 1963 5. Perloff JK, de Leon AC, O’Doherty D: The cardiomyopathy of progressive muscular dystrophy. Circulation 33:625-648, 1966 6. Lascelles RG, Barker IA, Thomas PK: Hereditary polyneuropathy of Roussy-Levy type with associated cardiomyopathy. Guy’s Hosp Rep 119:253-262, 1970 7. Sutterland JM: Familial spastic paraplegia. Its relation to mental and cardiac abnormalities. Lancet 2:169-l 70, 1957 8. Tanaka H, Niimura T, Kashima T, et al: Cardiomyopathy with hereditary cerebellar ataxia. Report of an autopsied case. Jpn Heart J 13:369-377, 1972 9. Littler WA: Heart block and peroneal muscular atrophy. A family study. Q J Med 39:431-439, 1970 10. Mawatari S, Katayama K: Scapuloperoneal muscular atrophy with cardiopathy. An X-linked recessive trait. Arch Neurol 28:55-59, 1973 11. Markesberg WI?, Griggs RC, Leach RP, et al: Late onset hereditary distal myopathy. Neurology (Minneap) 24:127-134, 1974 12. Uppal SC: Kearns’ syndrome, a new form of cardiomyopathy. Br Heart J 351766-769, 1973 13. Takahashi T, Nakamura H, Nakashima R: Scapuloperoneal dystrophy associated with neurogenic changes. J Neurol Sci 23: 575-583, 1974 14. Wohlfarl G, Fex J, Eliassert S: Hereditary proximal spinal muscular atrophy: a clinical entity simulating progressive muscular dystrophy. Acta Psychiatr Neurol Stand 30:395-406, 1955 15. Kugelberg E, Welander L: Heredofamilial juvenile muscular atrophy simulating muscular dystrophy. Arch Neurol Psychiatr 75:500-509, 1956
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16. Scherlag BJ, Lau SH, Helfant RH, et al: Catheter technique for recording of His bundle activity in man. Circulation 39:13-18, 1969 17. Narula OS, Scherlag BJ, Samet P, et al: Atrioventricular block. Localization and classification by His bundle recordings. Am J Med 50:146-165, 1971 18. Feigenbaum H: Echocardiography. Philadelphia, Lea & Febiger, 1973, p 216 19. Konno S, Sakakibara S: Endomyocardial biopsy. Dis Chest 44: 345-350, 1963 20. Rosen KM: The contribution of His bundle recording to the understanding of cardiac conduction in man. Circulation 43:961-966, 1971 21. Sterz H, Harrer G, Marchet HP, et al: Primare und neurogene Skeletmuskelerkrankungen bzw.-paralysen mit schweren kardialen Rhythmstbrungen. Z Kreislaufforsch 60: l- 13, 197 1 22. Matsumoto K, Kakiuchi F, Kaklhana M, et al: Kugelberg-Welander disease with cardiopathy of unknown etiology. Clinical report of a case. Respiration and Circulation 19:863-870, 1971 (in Japanese with English abstract) 23. Sugimura F, lijima M, Ozawa Y, et al: Two cases of KugelbergWelander’s disease with cardiopathy. Clin Neurol (Tokyo) 13: 79-86, 1973 (in Japanese with English abstract) 24. Maron BJ, Ferrans VC, Roberts WC: Ultrastructural features of degenerated cardiac muscle cells in patients with cardiac hypertrophy. Am J Pathol 79:387-434, 1975 25. Zoneraich S, Zoneraich 0, Rhee JJ: Echocardiographic findings in atrial flutter. Circulation 52:455-459, 1975 26. Hausmanowa-Petrusewicz I, Askanas W, Badurska B, et al: Infantile and juvenile spinal muscular atrophy. J Neurol Sci 6: 269-287, 1968 27. Kondo K: Beitrag zur “pseudodystrophischen” Natur der Amyotrophie bei der Wohlfart-Kugelberg-Welanderschen Krankheit. Acta Neuropathol (Berl) 13:29-42, 1969 28. Mastaglia FL, Walton JN: Histological and histochemical changes in skeletal muscle from cases of chronic juvenile and early adult spinal muscular atrophy (the Kugelberg-Welander syndrome). J Neurol Sci 12:15-44, 1971
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