Journal of
J. Neurol. 214, 301--304 (1977)
rOoc
~) by Springer-Verlag1977
Probable Thomsen's Disease with Cardiac Involvement Case Report Milne Anderson The Queen Elizabeth Hospital, Birmingham B 15 2 TH, England
Zusammenfassung. Pathologische Myocardver~inderungen in Myotonia dystrophica sind bekannt. Es gibt keine Berichte tiber pathologische Ver~inderungen des Myocards bei der Myotonia congenita (Thomsen). Ein Fall von m/Sglicher Thomsenscher Krankheit, kompliziert durch Herzsch~idigung, bei einem M a n n mit episodischen HerzrhythmusstSrungen mit Bewul~tlosigkeit wird beschrieben. Key words: Myotonia congenita - Thomsen's disease - Cardiac dysrhythmia Heart block.
Myotonia congenita has been recognized as a clinical entity since its description by Thomsen in 1867 [l l]. It is characterized by autosomal dominant inheritance, early appearance of myotonia and association with diffuse hypertrophy of muscle. In contrast, the typical m y o p a t h y of myotonia dystrophica affects the muscles of face and neck, and predominates distally in the limbs. A further distinction from myotonia dystrophica is that Thomsen's disease does not share the nonneurological abnormalities of the former: frontal baldness, cataracts, gonadal atrophy, and dysfunction of insulin and immunoglobulin metabolism. Cardiac involvement is c o m m o n in myotonia dystrophica, and is said not to occur in Thomsen's disease. The details of a patient with myotonia congenita, who suffered from syncopal attacks due to episodes of cardiac dysrhythmia caused by heart block, are reported.
Case Report Born in 1938 he was first seen in a medical clinic at the age of 16, when he complained of 'stiffness of his muscles', and noticed that, when he seized an object with his hands and came to release it, his muscles would not relax. Initially his symptoms were felt to be hysterical. Ten years later, aged 26, he complained of short-lived attacks of retrosternal and right upper quadrant abdominal pain, unrelated to food or exercise, and not relieved by antacids.
302
M. Anderson
Fig. 1. ECG LEADS V~ and V 2 showing 2nd degree heart block with Wenckebach's phenomenon
Examination revealed myotonia of grip, percussion myotonia, and irregularity oftbe pulse, but no other abnormality. Investigation showed normal values of plasma urea, electrolytes, calcium, phosphorus, sugar, and protein electrophoresis. X-ray of the chest and a barium meal were normal. Electrocardiography (ECG) on several occasions showed normal QRS complexes and second degree heart block with Wenckebach's phenomenon (Fig. 1), and on other occasions normal sinus rhythm. The other members of his family were examined. His father, who was clinically well, had first degree heart block, the PR interval being 0.28 sec. His mother, three sisters, and two brothers, were all normal, with normal ECGs. None showed evidence of myotonia. No treatment was considered necessary, and he failed to attend for review. Three years later he was seen at another hospital. His complaint now was of 'blackouts', of which he had suffered 12 attacks in the preceding 16 years. He experienced no warning or prodromal symptoms, lost consciousness for up to 5 min at a time, and exhibited no convulsive manifestations. A year before he had received treatment for depression with 'nerve tablets' in a psychiatric hospital. Examination once again showed myotonia of grip and on percussion, no evidence of dystrophy, and the pulse was irregular. X-rays of the chest and skull were normal; an ECG again showed Wenkebach's phenomenon, and an electroencephalogram (EEG) showed a slight excess of theta activity and was otherwise normal. It was unclear whether these episodes were epileptic or a form of Stokes-Adams attacks related to heart block. Treatment with phenytoin was recommended (with the hope that myotonia would be improved as well), and he was kept under review. The attacks continued and treatment was changed to long-acting isoprenaline, but he was unable to tolerate this, and was readmitted to hospital in 1972. Examination as before revealed widespread myotonia provoked by muscular activity and percussion; there was no evidence of dystrophy, and his pulse remained irregular. Results of haematological and biochemical investigations, including creatine kinase, were normal. X-rays of chest and skull, and an EEG were normal, as was the cerebrospinal fluid. Electromyography showed myotonic discharges in all the muscles sampled, and there were no features of myopathy. He refused muscle biopsy. ECG again showed second degree heart block with Wenckebach's phenomenon. His bundle electrography (Dr. D. O. Williams) demonstrated an intermittent Wenckebach conduction disturbance at AV nodal level; intraventricular conduction was normal. It was felt that his syncopal attacks were related to cardiac dysrhythmia, and treatment with an implanted pacemaker was offered but this the patient refused. He failed to attend again for review.
Discussion T h a t t h e d i a g n o s i s i n t h i s c a s e is o f T h o m s e n ' s d i s e a s e r a t h e r t h a n m y o t o n i a d y s t r o p h i c a s e e m s h i g h l y p r o b a b l e s i n c e b y t h e a g e o f 38, 20 y e a r s a f t e r m y o t o n i a
Probable Thomsen's Disease with Cardiac Involvement
303
was initially diagnosed, no features of m y o p a t h y have been found clinically or electromyographically and the blood creatine kinase level has remained normal. Unfortunately we have been unable to obtain a muscle biopsy. Further pointers in favor of Thomsen's disease are the absence of the non-neurological features of myotonia dystrophica: frontal baldness, gonadal atrophy, cataracts, and immunoglobulin abnormalities. Involvement of the heart has been a well-recognized feature of myotonia dystrophica [2, 5, 7, 8, 10] since its description by Griffiths in 1911 [6] and it is clinically recognizable in about 66% of patients. It takes the form of disturbances of conduction which may be intermittent, most commonly prolongation of the P R interval or QRS complex, and left bundle branch block. Syncope has been attributed to these abnormalities [3, 9] while in other cases cardiomegaly and congestive cardiac failure have occurred. Pathologically, the findings have been non-specific: fatty infiltration and replacement of myocardium, interstitial fibrosis, and varying degrees of destruction of muscle fibres. In one case with atrial fibrillation and flutter and various forms of intraventricular and AV block, serial sections of the pacemaker systems showed fibrosis and myocardial cell degeneration of the SA and AV nodes, and of the bundle of His to a lesser degree. Adjacent arteries showed varying degrees of cystic degeneration involving the ground substance of the tunica media [12]. Electronmicroscopy of another case disclosed vacuolation of sarcoplasmic reticulum and damage to mitochondria, and the suggestion was made that damage to the sarcoplasmic reticulum, which is associated with intracellular impulse transmission, may be responsible for the conduction defects [1]. Most authorities believe that the c o m m o n factors between the neurological and cardiac abnormalities are genetically determined, perhaps biochemical. The same hypothesis has been advanced for other neurological syndromes with cardiac involvement, such as Friedrich's ataxia and other muscular dystrophies. It has been stated that cardiac abnormality does not occur with myotonia congenita [7, 8, 10]. In the present case of myotonia congenita there were abnormalities of cardiac conduction similar to those found with myotonia dystrophica. The possibility exists that this is a chance coincidence of congenital heart block with myotonia congenita, but the likelihood that they are reflections of a c o m m o n genetically determined abnormality is more tempting. Perhaps more extensive cardiac investigation of patients with myotonia congenita will show that involvement of the heart is more c o m m o n than is now recognized.
Acknowledgements. Thanks are due to Dr. Michael Small for helpful comment, to Mr. T. F. Dee for photography, and to Mrs. Margaret Spanswick for secretarial help. References I. Bulloch, R. T., Davis, J. L., Hara, M.: Dystrophia myotonia with heart block: a light and electron microscopic study. Arch. Pathol. 84, 130--140 (1967) 2. Cannon, P. J.: The heart and lungs in myotonic muscular dystrophy. Am. J. Med. 32, 765--775 (1962) 3. Church, S. C.: The heart in myotonia atrophica. Arch. Intern. Med. 119, 176--181 (1967)
304
M. Anderson
4. DeWind, L. T., Jones, R. J.: Cardiovascular observations in dystrophia myotonica. J. Am. med. Ass. 144, 299--303 (1950) 5. Fisch, C.: The heart in dystrophia myotonica. Am. Heart J. 41, 525--538 (1951) 6. Griffith, T. W.: On myotonia. Q. J. Med. 5, 229--249 (1911) 7. Orndahl, G., Thulesius, O., Enestrom, S., Dehlin, O.: The heart in myotonic disease. Acta med. Scand. 176, 479--491 (1964) 8. Perloff, J. K.: Cardiomyopathy. In: Cardiovascular Clinics. Vol. 4. No. 1. Philadelphia: Davis 1972 9. Petrovich, N. J., Dunn, M., Reed, W.: Myotonia dystrophica with A-V dissociation and Stokes-Adams attacks. Am. Heart J. 68, 391 (1964) 10. Spillane, J. D.: The heart in myotonia atrophica. Br. Heart J. 13, 343--347 (1951) 11. Thomsen, J.: Tonische Kr~impfe in willktirlich beweglichen Muskeln in Folge von ererbter psychischer Disposition (Ataxia muscularis?). Arch. f. Psychiat. 6, 702--718 (1876) 12. Thomson, A. M. P.: Dystrophia cordis myotonica studied by serial histology of the pacemaker and conduction system. J. Pathol. Bacteriol. 96, 285--295 (1968)
Received September 17, 1976
J. Neurol. 214, 301--304 (1977)
rOoc
~) by Springer-Verlag1977
Probable Thomsen's Disease with Cardiac Involvement Case Report Milne Anderson The Queen Elizabeth Hospital, Birmingham B 15 2 TH, England
Zusammenfassung. Pathologische Myocardver~inderungen in Myotonia dystrophica sind bekannt. Es gibt keine Berichte tiber pathologische Ver~inderungen des Myocards bei der Myotonia congenita (Thomsen). Ein Fall von m/Sglicher Thomsenscher Krankheit, kompliziert durch Herzsch~idigung, bei einem M a n n mit episodischen HerzrhythmusstSrungen mit Bewul~tlosigkeit wird beschrieben. Key words: Myotonia congenita - Thomsen's disease - Cardiac dysrhythmia Heart block.
Myotonia congenita has been recognized as a clinical entity since its description by Thomsen in 1867 [l l]. It is characterized by autosomal dominant inheritance, early appearance of myotonia and association with diffuse hypertrophy of muscle. In contrast, the typical m y o p a t h y of myotonia dystrophica affects the muscles of face and neck, and predominates distally in the limbs. A further distinction from myotonia dystrophica is that Thomsen's disease does not share the nonneurological abnormalities of the former: frontal baldness, cataracts, gonadal atrophy, and dysfunction of insulin and immunoglobulin metabolism. Cardiac involvement is c o m m o n in myotonia dystrophica, and is said not to occur in Thomsen's disease. The details of a patient with myotonia congenita, who suffered from syncopal attacks due to episodes of cardiac dysrhythmia caused by heart block, are reported.
Case Report Born in 1938 he was first seen in a medical clinic at the age of 16, when he complained of 'stiffness of his muscles', and noticed that, when he seized an object with his hands and came to release it, his muscles would not relax. Initially his symptoms were felt to be hysterical. Ten years later, aged 26, he complained of short-lived attacks of retrosternal and right upper quadrant abdominal pain, unrelated to food or exercise, and not relieved by antacids.
302
M. Anderson
Fig. 1. ECG LEADS V~ and V 2 showing 2nd degree heart block with Wenckebach's phenomenon
Examination revealed myotonia of grip, percussion myotonia, and irregularity oftbe pulse, but no other abnormality. Investigation showed normal values of plasma urea, electrolytes, calcium, phosphorus, sugar, and protein electrophoresis. X-ray of the chest and a barium meal were normal. Electrocardiography (ECG) on several occasions showed normal QRS complexes and second degree heart block with Wenckebach's phenomenon (Fig. 1), and on other occasions normal sinus rhythm. The other members of his family were examined. His father, who was clinically well, had first degree heart block, the PR interval being 0.28 sec. His mother, three sisters, and two brothers, were all normal, with normal ECGs. None showed evidence of myotonia. No treatment was considered necessary, and he failed to attend for review. Three years later he was seen at another hospital. His complaint now was of 'blackouts', of which he had suffered 12 attacks in the preceding 16 years. He experienced no warning or prodromal symptoms, lost consciousness for up to 5 min at a time, and exhibited no convulsive manifestations. A year before he had received treatment for depression with 'nerve tablets' in a psychiatric hospital. Examination once again showed myotonia of grip and on percussion, no evidence of dystrophy, and the pulse was irregular. X-rays of the chest and skull were normal; an ECG again showed Wenkebach's phenomenon, and an electroencephalogram (EEG) showed a slight excess of theta activity and was otherwise normal. It was unclear whether these episodes were epileptic or a form of Stokes-Adams attacks related to heart block. Treatment with phenytoin was recommended (with the hope that myotonia would be improved as well), and he was kept under review. The attacks continued and treatment was changed to long-acting isoprenaline, but he was unable to tolerate this, and was readmitted to hospital in 1972. Examination as before revealed widespread myotonia provoked by muscular activity and percussion; there was no evidence of dystrophy, and his pulse remained irregular. Results of haematological and biochemical investigations, including creatine kinase, were normal. X-rays of chest and skull, and an EEG were normal, as was the cerebrospinal fluid. Electromyography showed myotonic discharges in all the muscles sampled, and there were no features of myopathy. He refused muscle biopsy. ECG again showed second degree heart block with Wenckebach's phenomenon. His bundle electrography (Dr. D. O. Williams) demonstrated an intermittent Wenckebach conduction disturbance at AV nodal level; intraventricular conduction was normal. It was felt that his syncopal attacks were related to cardiac dysrhythmia, and treatment with an implanted pacemaker was offered but this the patient refused. He failed to attend again for review.
Discussion T h a t t h e d i a g n o s i s i n t h i s c a s e is o f T h o m s e n ' s d i s e a s e r a t h e r t h a n m y o t o n i a d y s t r o p h i c a s e e m s h i g h l y p r o b a b l e s i n c e b y t h e a g e o f 38, 20 y e a r s a f t e r m y o t o n i a
Probable Thomsen's Disease with Cardiac Involvement
303
was initially diagnosed, no features of m y o p a t h y have been found clinically or electromyographically and the blood creatine kinase level has remained normal. Unfortunately we have been unable to obtain a muscle biopsy. Further pointers in favor of Thomsen's disease are the absence of the non-neurological features of myotonia dystrophica: frontal baldness, gonadal atrophy, cataracts, and immunoglobulin abnormalities. Involvement of the heart has been a well-recognized feature of myotonia dystrophica [2, 5, 7, 8, 10] since its description by Griffiths in 1911 [6] and it is clinically recognizable in about 66% of patients. It takes the form of disturbances of conduction which may be intermittent, most commonly prolongation of the P R interval or QRS complex, and left bundle branch block. Syncope has been attributed to these abnormalities [3, 9] while in other cases cardiomegaly and congestive cardiac failure have occurred. Pathologically, the findings have been non-specific: fatty infiltration and replacement of myocardium, interstitial fibrosis, and varying degrees of destruction of muscle fibres. In one case with atrial fibrillation and flutter and various forms of intraventricular and AV block, serial sections of the pacemaker systems showed fibrosis and myocardial cell degeneration of the SA and AV nodes, and of the bundle of His to a lesser degree. Adjacent arteries showed varying degrees of cystic degeneration involving the ground substance of the tunica media [12]. Electronmicroscopy of another case disclosed vacuolation of sarcoplasmic reticulum and damage to mitochondria, and the suggestion was made that damage to the sarcoplasmic reticulum, which is associated with intracellular impulse transmission, may be responsible for the conduction defects [1]. Most authorities believe that the c o m m o n factors between the neurological and cardiac abnormalities are genetically determined, perhaps biochemical. The same hypothesis has been advanced for other neurological syndromes with cardiac involvement, such as Friedrich's ataxia and other muscular dystrophies. It has been stated that cardiac abnormality does not occur with myotonia congenita [7, 8, 10]. In the present case of myotonia congenita there were abnormalities of cardiac conduction similar to those found with myotonia dystrophica. The possibility exists that this is a chance coincidence of congenital heart block with myotonia congenita, but the likelihood that they are reflections of a c o m m o n genetically determined abnormality is more tempting. Perhaps more extensive cardiac investigation of patients with myotonia congenita will show that involvement of the heart is more c o m m o n than is now recognized.
Acknowledgements. Thanks are due to Dr. Michael Small for helpful comment, to Mr. T. F. Dee for photography, and to Mrs. Margaret Spanswick for secretarial help. References I. Bulloch, R. T., Davis, J. L., Hara, M.: Dystrophia myotonia with heart block: a light and electron microscopic study. Arch. Pathol. 84, 130--140 (1967) 2. Cannon, P. J.: The heart and lungs in myotonic muscular dystrophy. Am. J. Med. 32, 765--775 (1962) 3. Church, S. C.: The heart in myotonia atrophica. Arch. Intern. Med. 119, 176--181 (1967)
304
M. Anderson
4. DeWind, L. T., Jones, R. J.: Cardiovascular observations in dystrophia myotonica. J. Am. med. Ass. 144, 299--303 (1950) 5. Fisch, C.: The heart in dystrophia myotonica. Am. Heart J. 41, 525--538 (1951) 6. Griffith, T. W.: On myotonia. Q. J. Med. 5, 229--249 (1911) 7. Orndahl, G., Thulesius, O., Enestrom, S., Dehlin, O.: The heart in myotonic disease. Acta med. Scand. 176, 479--491 (1964) 8. Perloff, J. K.: Cardiomyopathy. In: Cardiovascular Clinics. Vol. 4. No. 1. Philadelphia: Davis 1972 9. Petrovich, N. J., Dunn, M., Reed, W.: Myotonia dystrophica with A-V dissociation and Stokes-Adams attacks. Am. Heart J. 68, 391 (1964) 10. Spillane, J. D.: The heart in myotonia atrophica. Br. Heart J. 13, 343--347 (1951) 11. Thomsen, J.: Tonische Kr~impfe in willktirlich beweglichen Muskeln in Folge von ererbter psychischer Disposition (Ataxia muscularis?). Arch. f. Psychiat. 6, 702--718 (1876) 12. Thomson, A. M. P.: Dystrophia cordis myotonica studied by serial histology of the pacemaker and conduction system. J. Pathol. Bacteriol. 96, 285--295 (1968)
Received September 17, 1976
