Acta Med Scand 203: 39-42, 1978
Third Degree Atrioventricular Block, Chronic Progressive External Ophthalmoplegia and Pigmentary Degeneration of Retina Case Report and Survey of the Literature
Erik la Cour Petersen From the Department of Cardiology, University Hospital, Arhus, Denmark
ABSTRACT. A woman was noted to have chronic progressive external ophthalmoplegia, pigmentary degeneration of retina and third degree AV block. She was admitted to hospital because of syncopes and was successrUUy treated with a permanent pacemaker. Since 1958, 12 similar cases have been noted. Three of 7 patients without pacemaker treatment died, and 5 were successfully treated with pacemaker. The disturbances in AV conduction are not thought to be a mere coincidence to the ocular disorder. Cardiomyopathy has been suggested.
It is well known that cardiac involvement is an often recognized feature of different kinds of neuromuscular disorders. Since 1958, AV conduction disturbances have been described in patients with cronic progressive external ophthalmoplegia (CPEO) and pigmentary degeneration of retina. AV block is a lifethreatening complication to a harmless disorder of the ocular muscles.
CASE REPORT A 24-year-old female sewer had for 12 years noticed a gradually developing ptosis on both eyes. She and her family never thought it abnormal or unusual and never went to see a doctor. There was a family history of hemicrania, and from earliest childhood the patient had had attacks of headache accompanied by vomiting and photophobia. The patient had for 6 months suffered from spells of unconsciousness, when she was admitted to a local hospital in March 1974 after such an attack. She had third
degree A V block with a ventricular rate of 20/min and was immediately transferred to our Department of Cardiology. Examination at the time of admission showed a woman of small stature, exhausted and apathetic. ECG revealed third degree AV block with a ventricular rate of 24/min (Fig. I). A transvenous right ventricular pacing catheter, type Elema 588, was inserted and connected to an external pacemaker. A few days later an Elema 154 demand pacemaker was inserted subcutaneously on the left side of thorax. At the primary examination a grade 2 soft systolic murmur was heard at theleft sternal border. The murmur disappeared during artificial pacing. Chest X-ray on admission showed increased heart size (13/22 cm). One week later heart size was normal (10.Y22.5 cm). Neurological and ophthalmological examinations showed bilateral ptosis (Fig. 2) and severely restricted movements of the eyes both in vertical and horizontal plane and in convergence. Ophthalmoscopy showed a thin atrophic retina with scattered spots of pigment. The visual field was normal with preserved central vision, contrary to what is typically found in the classic retinitis pigmentosa. The skeletal muscles were somewhat poorly developed, but muscle strength and reflexes were within normal limits. During the pacemaker operation, a sample of skin and muscle was removed for examination. Histological examination showed no signs of neuromuscular disorder. No psychological test was carried out, but the IQ was estimated to be at the lower normal limit. The patient was shy and timid and, due to this, ocular muscle biopsy and spinal fluid examination were not carried out. Laboratory data, including complete RBC investigation, electrolytes in plasma, renal function, S-GOT,LDH, antistrcptolysin titer, antistreptococcal. hyaluronidase reaction, LE cell preparation, antinuclear factor and thyroid function, were all within normal limits. The patient has been followed in our Out-Patient Cliriic for 30 months. There have been no spells of fainting or dizziness. The AV block has been permanent, and the Acra Med Scand 203
40
E. la Cow Petersen
Fig. 1 . ECG showing third degree AV block with a ventricular rate of 24/mln.
pacemaker is functioning. There have been no cardiopulmonary symptoms and no other signs of cardiac involvement.
COMMENTS Heart disease is common in primary myopathies (9, 12, 15). Post mortem examinations have shown myocardial changes similar to those found in skeletal muscles. James (4) also found degenerative changes in the vessels supplying the sinus node and the AV node. CPEO starts with ptosis in the first or second decade of life, followed by increasing immobility of the extraocular muscles. The pupil is spared. Except for weakness of the facial muscles in some cases, involvement of skeletal muscles cannot be demonstrated. CPEO is often associated with a peculiar pigmentation of retina different from retinitis pigmentosa (5). Von Graefe was the first to describe the disorder in 1868 (2), and since then, a number of similar cases have been published. At first it was considered a disorder of the nervous system, but in 1946 Sandifer (13) demonstrated, with a rectus externus biopsy, that it seemed to be a myopathy rather than a disorder of the nervous system. His patient had bradycardia and bundle branch block, and so he was the first to suggest a possible heart involvement in CPEO. In 1958 Kearns and Sayre (6) published two cases of CPEO and pigmentary degeneration of retina complicated with third degree AV block. Since then a few similar cases have been published. Including the present case, the total number is 13. Table I shows relevant clinical data from all the cases published with CPEO, pigmentary degeneration of retina and third degree AV block, the latter verified at least once. Cases with only lesser disturAcro Med Scond 203
bances of conduction (5) are omitted. Females and males are equally represented. Ocular symptoms in most cases preceded cardiac symptoms by several years, but the latter were the most common reason for admission to hospital. Table I 1 shows histopathological findings in some of the cases. Skeletal muscle biopsy or necropsy disclosed abnormalities in two cases of 6 examined. Ocular muscle biopsy or necropsy showed changes similar to those found in primary myopathy in all 4 cases examined. In all 3 fatal cases, post mortem examination of the heart was performed. In two of them (2, 6) no abnormalities were disclosed, but in the third case ( 5 ) examination showed enlarged hyperchromatic muscle nucleus, focal subendothe-
Fig. 2. The patient with apparent bilateral ptosis and restricted movements of the eyes.
AV block, CPEO and pigmentary degeneration of retina
41
Table I. Clinical data on 13 patients with chronic progressive external ophthalmoplegia, pigmentary degeneration of retina and third degree AV block Case no. author, year, ref. no.
Duration of eye symptoms
(Y.)
Sex
(Y.)
Duration ofheart symptoms
34
d
14
8 years
Syncope
None
-
None
17
6
14
2 months
Syncope
Epinephrine
None
13
8
3
None
Ocular disease
Ephedrine, isoproterenol
+ +
None
4 Kearns 1965 (5)
35
0
19
2 weeks
Ptosis, syncope
None
-
None
5 Kearns 1965 (5)
34
d
17
17 years
None Cardiac incompensation
-
None
17
d
14
2 months
Syncope
None
+
None
16
0
8
1 year
Ocular disease, syncope
Isoproterenol
-
None
27
d
14
4 months
Syncope
Pacemaker
-
None
23
d
10
6 months
Syncope
Pacemaker
-
None
17
0
II
2 days
Syncope
Pacemaker
-
20 months
16
0
5
None
Pacemaker
-
None
12 Pilling & Nanton 1974 (10)
Ocular disease
23
P
3
Few hours
Syncope
Pacemaker
-
20 months
13 Present author 1977
24
P
12
6 months
Syncope
Pacemaker
-
30 months
1 Kearns& Sayre 1958 (6) 2 Kearns & Sayre 1958 (6) 3 Jageretal. 1960 (3)
6 Kearns 1965 (5) 7 Drachman 1(1) 8 Drachman 1(1) 9 Ross et al. 1969 (1 1) 10 Shastri et al. 1971 (14) 1 I Moniss et al. 1972 (8)
Age
lial fibrosis and a slightly thickened endocardium. The changes were believed to be responsible for the conduction disturbances. Six cases, all diagnosed after 1%5, received pacemaker treatment. Followup data are available on 3 patients. The pacemaker treatment had eliminated the tendency to syncope. Without pacemaker treatment the prognosis seems to be serious. Before the pacemaker era, 3 patients out of 7 died due to syncope. Treatment with pacemaker seems to improve the prognosis, though follow-up information is available on half of the cases only. It may be questioned, whether the cases published until now (Table I) represent a clinical entity. However, other features than AV block and ocular involvement were present in all cases: The
Cause of admission
Treatment of AV block
Death
UP
Follow-
patients were small and slightly built, with poorly developed skeletal muscles. IQ was estimated to be at the lower end of the normal range. Increased protein in the spinal fluid was found in all patients who had this examination. Chromosome analysis turned out normal. No familiar predisposition has been demonstrated. The ocular disease without cardiac involvement seems to be rather infrequent. Kiloh and Nevin (7) found reports of 99 cases. It is generally regarded as an inconvenient but harmless disorder, but when complicated with third degree AV block, the condition becomes dangerous. It demands prompt pacemaker therapy. In patients with ptosis or other signs of ocular myopathy, ECG must be recommended in order to disclose AV conduction disturActa Med Scond 203
42
E . la Cour Petersen
Table 11. Histopathological findings in patients with chronic progressive external ophthalmoplegia, pigmentary degeneration of retina and third degree AV block Case no.
3 4
10 11 12 13
Skeletal muscle examination
Ocular muscle examination
Histological examination of the heart
None Necropsy : normal Necropsy : normal Biopsy: myopath y None None
None Necropsy : myopathy Necropsy: myopathy None
None Necropsy : normal Necropsy: normal None
None Necropsy : myopath y None Biopsy: myopathy None
None Necropsy"
None None None None
None None None None
None Biopsy: normal Biopsy: nearly normal None None None Biopsy: normal
None None None
Enlarged hyperchromatic muscle nucleus, focal subendothelial fibrosis and a slightly thickened endocardium.
(I
bances before progression to third degree block. Morriss et al. (8) showed that His bundle recording can be of some aid in doubtful cases.
REFERENCES I . Drachrnan, D. A.: Ophthalmoplegia plus. The neurodegenerative disorders associated with progressive external ophthalrnoplegia. Arch Neurol 18: 654, 1968.
Acta Med Scand 203
2. von Graefe, A.: Verhandlungen aerztlicher Gesellschaften. Berl Klin Wochenschr 5: 125, 1868. 3. Jager, B. V., Fred, H. L., Butler, R. B. & Carnes, W. H.: Occurrence of retinal pigmentation, ophthalrnoplegia, ataxia, deafness and heart block. Am J Med 29:888, 1960. 4. James, T. N.: Observations on cardiovascular involvement, including cardiac conducting system, in progressive muscular dystrophy. Am Heart J 63: 48, 1962. 5. Kearns, T. P.: External ophthalmoplegia, pigmentary degeneration of the retina, and cardiomyopathy: A newly recognized syndrome. Trans Am Ophthalmol SOC63: 559, 1%5. 6. Kearns, T. P. & Sayre, G. P.: Retinitis pigmentosa, external ophthalmoplegia and complete heart block. Arch Ophthalmol60: 280, 1958. 7. Kiloh, L. G. & Nevin, S.: Progressive dystrophy of the external ocular muscles (ocular myopathy). Brain 74: 115, 1951. 8. Morriss, J. H., Eugster, G. S., Nora, J. J. & Pryor, R.: His bundle recording in progressive external ophthalmoplegia. J Pediatr 81: 1167, 1972. 9. Perloff, J. K., De Leon, A. C., J r & ODoherty, D.: The cardiomyopathy of progressive muscular dystrophy. Circulation 33: 625, 1966. 10. Pilling, J. B. & Nanton, M. A.: Progressive external ophthalmoplegia and heart block. Br Med J 1:492, 1974. 1 1 . Ross, A,, Lipschutz, D., Austin, J. & Smith, J., Jr: External ophthalmoplegia and complete heart block. N Engl J Med 280: 313, 1%9. 12. Rubin, I . L. & Buchberg, A. S.: The heart in progressive muscular dystrophy. Am Heart J 43: 161, 1952. 13. Sandifer, P. H.: Cronic progressive ophthalmoplegia of myopathic origin. J Neurol Neurosurg Psychiatry 9:81, 1946. 14. Shastri, S. D., Tulgan, H., Budnitz, J. & Colker, J. L.: Progressive ophthalmoplegia, retinitis pigmentosa, and complete heart block, NY State J Med 71: 587, 1971. 15. Weisenfeld, S. & Messinger, W. J.: Cardiac involvement in progressive muscular dystrophy. Am Heart J 45: 170. 1952.
Third Degree Atrioventricular Block, Chronic Progressive External Ophthalmoplegia and Pigmentary Degeneration of Retina Case Report and Survey of the Literature
Erik la Cour Petersen From the Department of Cardiology, University Hospital, Arhus, Denmark
ABSTRACT. A woman was noted to have chronic progressive external ophthalmoplegia, pigmentary degeneration of retina and third degree AV block. She was admitted to hospital because of syncopes and was successrUUy treated with a permanent pacemaker. Since 1958, 12 similar cases have been noted. Three of 7 patients without pacemaker treatment died, and 5 were successfully treated with pacemaker. The disturbances in AV conduction are not thought to be a mere coincidence to the ocular disorder. Cardiomyopathy has been suggested.
It is well known that cardiac involvement is an often recognized feature of different kinds of neuromuscular disorders. Since 1958, AV conduction disturbances have been described in patients with cronic progressive external ophthalmoplegia (CPEO) and pigmentary degeneration of retina. AV block is a lifethreatening complication to a harmless disorder of the ocular muscles.
CASE REPORT A 24-year-old female sewer had for 12 years noticed a gradually developing ptosis on both eyes. She and her family never thought it abnormal or unusual and never went to see a doctor. There was a family history of hemicrania, and from earliest childhood the patient had had attacks of headache accompanied by vomiting and photophobia. The patient had for 6 months suffered from spells of unconsciousness, when she was admitted to a local hospital in March 1974 after such an attack. She had third
degree A V block with a ventricular rate of 20/min and was immediately transferred to our Department of Cardiology. Examination at the time of admission showed a woman of small stature, exhausted and apathetic. ECG revealed third degree AV block with a ventricular rate of 24/min (Fig. I). A transvenous right ventricular pacing catheter, type Elema 588, was inserted and connected to an external pacemaker. A few days later an Elema 154 demand pacemaker was inserted subcutaneously on the left side of thorax. At the primary examination a grade 2 soft systolic murmur was heard at theleft sternal border. The murmur disappeared during artificial pacing. Chest X-ray on admission showed increased heart size (13/22 cm). One week later heart size was normal (10.Y22.5 cm). Neurological and ophthalmological examinations showed bilateral ptosis (Fig. 2) and severely restricted movements of the eyes both in vertical and horizontal plane and in convergence. Ophthalmoscopy showed a thin atrophic retina with scattered spots of pigment. The visual field was normal with preserved central vision, contrary to what is typically found in the classic retinitis pigmentosa. The skeletal muscles were somewhat poorly developed, but muscle strength and reflexes were within normal limits. During the pacemaker operation, a sample of skin and muscle was removed for examination. Histological examination showed no signs of neuromuscular disorder. No psychological test was carried out, but the IQ was estimated to be at the lower normal limit. The patient was shy and timid and, due to this, ocular muscle biopsy and spinal fluid examination were not carried out. Laboratory data, including complete RBC investigation, electrolytes in plasma, renal function, S-GOT,LDH, antistrcptolysin titer, antistreptococcal. hyaluronidase reaction, LE cell preparation, antinuclear factor and thyroid function, were all within normal limits. The patient has been followed in our Out-Patient Cliriic for 30 months. There have been no spells of fainting or dizziness. The AV block has been permanent, and the Acra Med Scand 203
40
E. la Cow Petersen
Fig. 1 . ECG showing third degree AV block with a ventricular rate of 24/mln.
pacemaker is functioning. There have been no cardiopulmonary symptoms and no other signs of cardiac involvement.
COMMENTS Heart disease is common in primary myopathies (9, 12, 15). Post mortem examinations have shown myocardial changes similar to those found in skeletal muscles. James (4) also found degenerative changes in the vessels supplying the sinus node and the AV node. CPEO starts with ptosis in the first or second decade of life, followed by increasing immobility of the extraocular muscles. The pupil is spared. Except for weakness of the facial muscles in some cases, involvement of skeletal muscles cannot be demonstrated. CPEO is often associated with a peculiar pigmentation of retina different from retinitis pigmentosa (5). Von Graefe was the first to describe the disorder in 1868 (2), and since then, a number of similar cases have been published. At first it was considered a disorder of the nervous system, but in 1946 Sandifer (13) demonstrated, with a rectus externus biopsy, that it seemed to be a myopathy rather than a disorder of the nervous system. His patient had bradycardia and bundle branch block, and so he was the first to suggest a possible heart involvement in CPEO. In 1958 Kearns and Sayre (6) published two cases of CPEO and pigmentary degeneration of retina complicated with third degree AV block. Since then a few similar cases have been published. Including the present case, the total number is 13. Table I shows relevant clinical data from all the cases published with CPEO, pigmentary degeneration of retina and third degree AV block, the latter verified at least once. Cases with only lesser disturAcro Med Scond 203
bances of conduction (5) are omitted. Females and males are equally represented. Ocular symptoms in most cases preceded cardiac symptoms by several years, but the latter were the most common reason for admission to hospital. Table I 1 shows histopathological findings in some of the cases. Skeletal muscle biopsy or necropsy disclosed abnormalities in two cases of 6 examined. Ocular muscle biopsy or necropsy showed changes similar to those found in primary myopathy in all 4 cases examined. In all 3 fatal cases, post mortem examination of the heart was performed. In two of them (2, 6) no abnormalities were disclosed, but in the third case ( 5 ) examination showed enlarged hyperchromatic muscle nucleus, focal subendothe-
Fig. 2. The patient with apparent bilateral ptosis and restricted movements of the eyes.
AV block, CPEO and pigmentary degeneration of retina
41
Table I. Clinical data on 13 patients with chronic progressive external ophthalmoplegia, pigmentary degeneration of retina and third degree AV block Case no. author, year, ref. no.
Duration of eye symptoms
(Y.)
Sex
(Y.)
Duration ofheart symptoms
34
d
14
8 years
Syncope
None
-
None
17
6
14
2 months
Syncope
Epinephrine
None
13
8
3
None
Ocular disease
Ephedrine, isoproterenol
+ +
None
4 Kearns 1965 (5)
35
0
19
2 weeks
Ptosis, syncope
None
-
None
5 Kearns 1965 (5)
34
d
17
17 years
None Cardiac incompensation
-
None
17
d
14
2 months
Syncope
None
+
None
16
0
8
1 year
Ocular disease, syncope
Isoproterenol
-
None
27
d
14
4 months
Syncope
Pacemaker
-
None
23
d
10
6 months
Syncope
Pacemaker
-
None
17
0
II
2 days
Syncope
Pacemaker
-
20 months
16
0
5
None
Pacemaker
-
None
12 Pilling & Nanton 1974 (10)
Ocular disease
23
P
3
Few hours
Syncope
Pacemaker
-
20 months
13 Present author 1977
24
P
12
6 months
Syncope
Pacemaker
-
30 months
1 Kearns& Sayre 1958 (6) 2 Kearns & Sayre 1958 (6) 3 Jageretal. 1960 (3)
6 Kearns 1965 (5) 7 Drachman 1(1) 8 Drachman 1(1) 9 Ross et al. 1969 (1 1) 10 Shastri et al. 1971 (14) 1 I Moniss et al. 1972 (8)
Age
lial fibrosis and a slightly thickened endocardium. The changes were believed to be responsible for the conduction disturbances. Six cases, all diagnosed after 1%5, received pacemaker treatment. Followup data are available on 3 patients. The pacemaker treatment had eliminated the tendency to syncope. Without pacemaker treatment the prognosis seems to be serious. Before the pacemaker era, 3 patients out of 7 died due to syncope. Treatment with pacemaker seems to improve the prognosis, though follow-up information is available on half of the cases only. It may be questioned, whether the cases published until now (Table I) represent a clinical entity. However, other features than AV block and ocular involvement were present in all cases: The
Cause of admission
Treatment of AV block
Death
UP
Follow-
patients were small and slightly built, with poorly developed skeletal muscles. IQ was estimated to be at the lower end of the normal range. Increased protein in the spinal fluid was found in all patients who had this examination. Chromosome analysis turned out normal. No familiar predisposition has been demonstrated. The ocular disease without cardiac involvement seems to be rather infrequent. Kiloh and Nevin (7) found reports of 99 cases. It is generally regarded as an inconvenient but harmless disorder, but when complicated with third degree AV block, the condition becomes dangerous. It demands prompt pacemaker therapy. In patients with ptosis or other signs of ocular myopathy, ECG must be recommended in order to disclose AV conduction disturActa Med Scond 203
42
E . la Cour Petersen
Table 11. Histopathological findings in patients with chronic progressive external ophthalmoplegia, pigmentary degeneration of retina and third degree AV block Case no.
3 4
10 11 12 13
Skeletal muscle examination
Ocular muscle examination
Histological examination of the heart
None Necropsy : normal Necropsy : normal Biopsy: myopath y None None
None Necropsy : myopathy Necropsy: myopathy None
None Necropsy : normal Necropsy: normal None
None Necropsy : myopath y None Biopsy: myopathy None
None Necropsy"
None None None None
None None None None
None Biopsy: normal Biopsy: nearly normal None None None Biopsy: normal
None None None
Enlarged hyperchromatic muscle nucleus, focal subendothelial fibrosis and a slightly thickened endocardium.
(I
bances before progression to third degree block. Morriss et al. (8) showed that His bundle recording can be of some aid in doubtful cases.
REFERENCES I . Drachrnan, D. A.: Ophthalmoplegia plus. The neurodegenerative disorders associated with progressive external ophthalrnoplegia. Arch Neurol 18: 654, 1968.
Acta Med Scand 203
2. von Graefe, A.: Verhandlungen aerztlicher Gesellschaften. Berl Klin Wochenschr 5: 125, 1868. 3. Jager, B. V., Fred, H. L., Butler, R. B. & Carnes, W. H.: Occurrence of retinal pigmentation, ophthalrnoplegia, ataxia, deafness and heart block. Am J Med 29:888, 1960. 4. James, T. N.: Observations on cardiovascular involvement, including cardiac conducting system, in progressive muscular dystrophy. Am Heart J 63: 48, 1962. 5. Kearns, T. P.: External ophthalmoplegia, pigmentary degeneration of the retina, and cardiomyopathy: A newly recognized syndrome. Trans Am Ophthalmol SOC63: 559, 1%5. 6. Kearns, T. P. & Sayre, G. P.: Retinitis pigmentosa, external ophthalmoplegia and complete heart block. Arch Ophthalmol60: 280, 1958. 7. Kiloh, L. G. & Nevin, S.: Progressive dystrophy of the external ocular muscles (ocular myopathy). Brain 74: 115, 1951. 8. Morriss, J. H., Eugster, G. S., Nora, J. J. & Pryor, R.: His bundle recording in progressive external ophthalmoplegia. J Pediatr 81: 1167, 1972. 9. Perloff, J. K., De Leon, A. C., J r & ODoherty, D.: The cardiomyopathy of progressive muscular dystrophy. Circulation 33: 625, 1966. 10. Pilling, J. B. & Nanton, M. A.: Progressive external ophthalmoplegia and heart block. Br Med J 1:492, 1974. 1 1 . Ross, A,, Lipschutz, D., Austin, J. & Smith, J., Jr: External ophthalmoplegia and complete heart block. N Engl J Med 280: 313, 1%9. 12. Rubin, I . L. & Buchberg, A. S.: The heart in progressive muscular dystrophy. Am Heart J 43: 161, 1952. 13. Sandifer, P. H.: Cronic progressive ophthalmoplegia of myopathic origin. J Neurol Neurosurg Psychiatry 9:81, 1946. 14. Shastri, S. D., Tulgan, H., Budnitz, J. & Colker, J. L.: Progressive ophthalmoplegia, retinitis pigmentosa, and complete heart block, NY State J Med 71: 587, 1971. 15. Weisenfeld, S. & Messinger, W. J.: Cardiac involvement in progressive muscular dystrophy. Am Heart J 45: 170. 1952.
