1321
Our fmdings confirm that the FSHD gene lies on the distal long of chromosome 4 and suggests that there is a single genetic locus for this disease. This homogeneity accords with analyses of the clinical patterns in these and other families.8 The family in which FSH-type spinal muscular atrophy was diagnosed in some members had linkage results concordant with those in families classified as a muscular dystrophy. An analogous diagnostic misclassification has happened in patients with Becker muscular dystrophy, recognised by dystrophin gene deletion but previously categorised as X-linked spinal muscular atrophy.9 In FSHD families with tight linkage, probe D4S 139 looks to be a suitable marker for presymptomatic, carrier, and antenatal testing. arm
We thank Dr George Padberg (Leiden) for telling us about the linkage result with D4S171; Dr E. Milner and Dr J. Murray for donating DNA probes; the clinicians who referred families (especially Prof R. Edwards and Dr Robin Fitzsimons); Prof Alistair Compston for encouragement and clinical guidance; the Muscular Dystrophy Group of Great Britain for funding and the many patients and families for their cooperation. Institute of Medical Genetics, University of Wales College of Medicine,
Cardiff
(UWCM)
M. UPADHYAYA
Institute of Medical Genetics UWCM, and Bristol Children’s Hospital
P. W. LUNT
Department of Pediatrics, University of Connecticut Health Center, Framington, Connecticut, USA
M. SARFARAZI
Institute of Medical Genetics, UWCM
W. BROADHEAD J. DANIELS
Institute of Medical Genetics, and Department of Psychological Medicine, UWCM
M. OWEN
Institute of Medical Genetics, UWCM, Cardiff CF4 4XN, UK
P. S. HARPER
1. Walton J, Gardner-Medwin D. The muscular dystrophies. In: Walton J, ed. Disorders of voluntary muscle, 5th ed. Edinburgh: Churchill Livingstone, 1988:
chap 15. 2. Lunt PW. A workshop on facioscapulohumeral (Landouzy-Dejerine) disease. J Med Genet 1989. 26: 535-37. 3. Sarfarazi M, Upadhyaya M, Padberg G, et al. An exclusion map for facioscapulohumeral (Landouzy-Dejerine) disease. J Med Genet 1989; 26: 481-84. 4. Upadyaya M, Sarfarazi M, Lunt PW, Broadhead W, Harper PS. A genetic linkage study of facioscapulohumeral (Landouzy-Dejerine) disease with 24 polymorphic DNA probes. J Med Genet 1989; 26: 490-93. 5. Lunt PW, Compston DAS, Harper PS. Estimation of age dependent penetrance in facioscapulohumeral muscular dystrophy by minimising ascertainment bias. J Med Genet 1989; 26: 755-60. 6. Weber JL, May PE. Dinucleotide repeat polymorphism at D5S171 locus. Nucleic Add Res 1990; 18: 2202. 7. Milner ECB, Lotshaw CL, Van Dijk W, et al. Isolation and mapping of a polymorphic DNA sequence pH30 on chromosome 4. Nucleic Acid Res 1989; 17: 4002. 8. Lunt PW. Facioscapulohumeral disease: heterogeneity or homogeneity? Abstracts of the VIIth International Congress on Neuromuscular Diseases (Munich, Sept 16-22, 1990). J Neurol Sci 1990; 98 (suppl): 196. 9. Lunt PW, Cumming WJC, Kingston H, et al. DNA probes in differential diagnosis of Becker muscular dystrophy and spinal muscular atrophy Lancet 1989; i: 46-47. 10. Boyes JW, Fraser FC, Lawler SD, McKenzie HJ. A pedigree of progressive muscular dystrophy. Ann Eugen 1950; 15: 46-51.
IIIJI]]II!III’II!" r 1,1,11!I!ill’III’IIIIII’!IIIII!II’I’1111111BII’1111111JIIIII
Continuous 2-lead ECG during apomorphine infusion.
days a continuous 8-hour iv infusion of apomorphine, at a constant rate of 3 mg/h, was given alone (day 2) and in association with oral domperidone (day 3). No other drugs were given. A continuous 2-lead ECG (Holter) was applied and systolic/diastolic blood pressure was recorded every 15 min, with an automatic noninvasive device. In this patient the trial had to be interrupted on the second day (apomorphine without domperidone) because of a syncopal attack 11 min after the infusion was started, which was preceded by a rapidly progressive fall in blood pressure (from 120/80 mm Hg to a minimum recorded value of 60/40 mm Hg). The infusion was immediately stopped and the patient’s condition promptly stabilised without management. 10 min after the start of the infusion (at onset of mild nausea) a progressive and striking sinus was seen (figure) (heart rate 34 bpm), culminating, simultaneously with the syncope, in a 17 s sinus arrest, interrupted
bradycardia
only by one junctional escape beat at 5 s. The restoration of normal sinus rhythm was preceded by a transient junctional escape rhythm, at 30 bpm. No hypokinetic arrhythmias were seen on the first day and during a subsequent 48-h Holter recording. Repeated standard 12-lead ECG and enzyme values, including creatine kinase-MB, were normal. Vagal stimulation (Valsalva manoeuvre, carotid sinus pressure) done a week later did not induce hypokinetic arrhythmias or significant bradycardia. It is well known that apomorphine can induce a dose-dependent reduction in blood pressure and heart rate, probably because of peripheral DAz receptor stimulation. The simultaneous administration of domperidone, a potent selective peripheral DA antagonist, seems to counteract these effects, besides neutralising the nausea and vomiting induced by apomorphine.4,5 However, despite premedication with domperidone, postural hypotension and vasovagal response with sc apomorphine has been reported in 9 of 100 patients with parkinsonism.6 No other cases of apomorphine-related hypokinetic arrhythmias have been documented. However, some reported adverse cardiovascular events might be related to misdiagnosed arrhythmia. Although there are other possibilities, the rapid onset of symptoms, the very low dose of apomorphine infused (03 mg), and the absence of cardiovascular risk factors, lead us to believe that the cardiac arrest we describe was related to individual drug hypersensitivity and therefore was not predictable. ANTONIO ATTANASIO
Transient cardiac arrest during continuous intravenous infusion of apomorphine
SIR,-Apomorphine is a potent dopamine receptor agonist that can be used parenterally in Parkinson’s disease.1,2 Because of the similar pharmacokinetics of subcutaneous (sc) and intravenous (iv) apomorphine a rapid onset of clinical effects can be achieved by both routes.3 We report a transient cardiac arrest in a patient with parkinsonism while he was receiving an iv infusion of apomorphine. A 41-year-old man, who had had Parkinson’s disease for 8 months, but who was not having treatment, was included in a trial to evaluate the cardiovascular effects of iv apomorphine. He was otherwise healthy, normotensive, and had no postural hypotension. Standard electrocardiography (ECG) showed a sinus rhythm with a heart
of 72 beats per minute (bpm); blood tests, chest and M-mode and two dimensional echocardiogram were normal. The drug trial was for three consecutive days: on day 1 an 8-hour iv infusion of saline (placebo) was given; during the next 2 rate
radiography,
Medical Clinic, Department of Internal Medicine, Tor Vergata University, 00161 Rome, Italy, and First Neurology Clinic, Department of Neurological Sciences, La Sapienza University, Rome
1. Stibe
AMBROGIO CAPRIA GIUSEPPE LEGGIADRO MASSIMO MICHISANTI DARIO CANNATA FABRIZIO STOCCHI STEFANO RUGGIERI
CMH, Lees AJ, Kempster PA, Stem GM. Subcutaneous apomorphine in parkinsonian on-off oscillations. Lancet 1988; i: 403-06. 2. Oertel WH, Gasser T, Ippish R, Trenkwalder C, Poewe W. Apomorphine test for dopaminergic responsiveness. Lancet 1989; i: 1262-63. 3. Gancher ST, Woodward WR, Boucher B, Nutt JG. Peripheral pharmacokinetics of apomorphine in humans. Ann Neurol 1989; 26: 232-38. 4. Rascol OJ, Montastruc JL. Cardiovascular effects of apomorphine in humans: evidence for peripheral mechanisms. Clin Neuropharmacol 1986; 9: 566-69. 5. Pollack P, Mallaret M, Gaio JM, Hommel M, Perret J. Blood pressure effects of apomorphine and domperidone in parkinsonism. In: Yahr MD, Bergmann KJ, eds. Advances in neurology. New York: Raven Press, 1986: 263-66. 6. Hughes AJ, Lees AJ, Stem GM. Apomorphine test to predict dopaminergic responsiveness in parkinsonian syndromes. Lancet 1990; 356: 32-34.
Our fmdings confirm that the FSHD gene lies on the distal long of chromosome 4 and suggests that there is a single genetic locus for this disease. This homogeneity accords with analyses of the clinical patterns in these and other families.8 The family in which FSH-type spinal muscular atrophy was diagnosed in some members had linkage results concordant with those in families classified as a muscular dystrophy. An analogous diagnostic misclassification has happened in patients with Becker muscular dystrophy, recognised by dystrophin gene deletion but previously categorised as X-linked spinal muscular atrophy.9 In FSHD families with tight linkage, probe D4S 139 looks to be a suitable marker for presymptomatic, carrier, and antenatal testing. arm
We thank Dr George Padberg (Leiden) for telling us about the linkage result with D4S171; Dr E. Milner and Dr J. Murray for donating DNA probes; the clinicians who referred families (especially Prof R. Edwards and Dr Robin Fitzsimons); Prof Alistair Compston for encouragement and clinical guidance; the Muscular Dystrophy Group of Great Britain for funding and the many patients and families for their cooperation. Institute of Medical Genetics, University of Wales College of Medicine,
Cardiff
(UWCM)
M. UPADHYAYA
Institute of Medical Genetics UWCM, and Bristol Children’s Hospital
P. W. LUNT
Department of Pediatrics, University of Connecticut Health Center, Framington, Connecticut, USA
M. SARFARAZI
Institute of Medical Genetics, UWCM
W. BROADHEAD J. DANIELS
Institute of Medical Genetics, and Department of Psychological Medicine, UWCM
M. OWEN
Institute of Medical Genetics, UWCM, Cardiff CF4 4XN, UK
P. S. HARPER
1. Walton J, Gardner-Medwin D. The muscular dystrophies. In: Walton J, ed. Disorders of voluntary muscle, 5th ed. Edinburgh: Churchill Livingstone, 1988:
chap 15. 2. Lunt PW. A workshop on facioscapulohumeral (Landouzy-Dejerine) disease. J Med Genet 1989. 26: 535-37. 3. Sarfarazi M, Upadhyaya M, Padberg G, et al. An exclusion map for facioscapulohumeral (Landouzy-Dejerine) disease. J Med Genet 1989; 26: 481-84. 4. Upadyaya M, Sarfarazi M, Lunt PW, Broadhead W, Harper PS. A genetic linkage study of facioscapulohumeral (Landouzy-Dejerine) disease with 24 polymorphic DNA probes. J Med Genet 1989; 26: 490-93. 5. Lunt PW, Compston DAS, Harper PS. Estimation of age dependent penetrance in facioscapulohumeral muscular dystrophy by minimising ascertainment bias. J Med Genet 1989; 26: 755-60. 6. Weber JL, May PE. Dinucleotide repeat polymorphism at D5S171 locus. Nucleic Add Res 1990; 18: 2202. 7. Milner ECB, Lotshaw CL, Van Dijk W, et al. Isolation and mapping of a polymorphic DNA sequence pH30 on chromosome 4. Nucleic Acid Res 1989; 17: 4002. 8. Lunt PW. Facioscapulohumeral disease: heterogeneity or homogeneity? Abstracts of the VIIth International Congress on Neuromuscular Diseases (Munich, Sept 16-22, 1990). J Neurol Sci 1990; 98 (suppl): 196. 9. Lunt PW, Cumming WJC, Kingston H, et al. DNA probes in differential diagnosis of Becker muscular dystrophy and spinal muscular atrophy Lancet 1989; i: 46-47. 10. Boyes JW, Fraser FC, Lawler SD, McKenzie HJ. A pedigree of progressive muscular dystrophy. Ann Eugen 1950; 15: 46-51.
IIIJI]]II!III’II!" r 1,1,11!I!ill’III’IIIIII’!IIIII!II’I’1111111BII’1111111JIIIII
Continuous 2-lead ECG during apomorphine infusion.
days a continuous 8-hour iv infusion of apomorphine, at a constant rate of 3 mg/h, was given alone (day 2) and in association with oral domperidone (day 3). No other drugs were given. A continuous 2-lead ECG (Holter) was applied and systolic/diastolic blood pressure was recorded every 15 min, with an automatic noninvasive device. In this patient the trial had to be interrupted on the second day (apomorphine without domperidone) because of a syncopal attack 11 min after the infusion was started, which was preceded by a rapidly progressive fall in blood pressure (from 120/80 mm Hg to a minimum recorded value of 60/40 mm Hg). The infusion was immediately stopped and the patient’s condition promptly stabilised without management. 10 min after the start of the infusion (at onset of mild nausea) a progressive and striking sinus was seen (figure) (heart rate 34 bpm), culminating, simultaneously with the syncope, in a 17 s sinus arrest, interrupted
bradycardia
only by one junctional escape beat at 5 s. The restoration of normal sinus rhythm was preceded by a transient junctional escape rhythm, at 30 bpm. No hypokinetic arrhythmias were seen on the first day and during a subsequent 48-h Holter recording. Repeated standard 12-lead ECG and enzyme values, including creatine kinase-MB, were normal. Vagal stimulation (Valsalva manoeuvre, carotid sinus pressure) done a week later did not induce hypokinetic arrhythmias or significant bradycardia. It is well known that apomorphine can induce a dose-dependent reduction in blood pressure and heart rate, probably because of peripheral DAz receptor stimulation. The simultaneous administration of domperidone, a potent selective peripheral DA antagonist, seems to counteract these effects, besides neutralising the nausea and vomiting induced by apomorphine.4,5 However, despite premedication with domperidone, postural hypotension and vasovagal response with sc apomorphine has been reported in 9 of 100 patients with parkinsonism.6 No other cases of apomorphine-related hypokinetic arrhythmias have been documented. However, some reported adverse cardiovascular events might be related to misdiagnosed arrhythmia. Although there are other possibilities, the rapid onset of symptoms, the very low dose of apomorphine infused (03 mg), and the absence of cardiovascular risk factors, lead us to believe that the cardiac arrest we describe was related to individual drug hypersensitivity and therefore was not predictable. ANTONIO ATTANASIO
Transient cardiac arrest during continuous intravenous infusion of apomorphine
SIR,-Apomorphine is a potent dopamine receptor agonist that can be used parenterally in Parkinson’s disease.1,2 Because of the similar pharmacokinetics of subcutaneous (sc) and intravenous (iv) apomorphine a rapid onset of clinical effects can be achieved by both routes.3 We report a transient cardiac arrest in a patient with parkinsonism while he was receiving an iv infusion of apomorphine. A 41-year-old man, who had had Parkinson’s disease for 8 months, but who was not having treatment, was included in a trial to evaluate the cardiovascular effects of iv apomorphine. He was otherwise healthy, normotensive, and had no postural hypotension. Standard electrocardiography (ECG) showed a sinus rhythm with a heart
of 72 beats per minute (bpm); blood tests, chest and M-mode and two dimensional echocardiogram were normal. The drug trial was for three consecutive days: on day 1 an 8-hour iv infusion of saline (placebo) was given; during the next 2 rate
radiography,
Medical Clinic, Department of Internal Medicine, Tor Vergata University, 00161 Rome, Italy, and First Neurology Clinic, Department of Neurological Sciences, La Sapienza University, Rome
1. Stibe
AMBROGIO CAPRIA GIUSEPPE LEGGIADRO MASSIMO MICHISANTI DARIO CANNATA FABRIZIO STOCCHI STEFANO RUGGIERI
CMH, Lees AJ, Kempster PA, Stem GM. Subcutaneous apomorphine in parkinsonian on-off oscillations. Lancet 1988; i: 403-06. 2. Oertel WH, Gasser T, Ippish R, Trenkwalder C, Poewe W. Apomorphine test for dopaminergic responsiveness. Lancet 1989; i: 1262-63. 3. Gancher ST, Woodward WR, Boucher B, Nutt JG. Peripheral pharmacokinetics of apomorphine in humans. Ann Neurol 1989; 26: 232-38. 4. Rascol OJ, Montastruc JL. Cardiovascular effects of apomorphine in humans: evidence for peripheral mechanisms. Clin Neuropharmacol 1986; 9: 566-69. 5. Pollack P, Mallaret M, Gaio JM, Hommel M, Perret J. Blood pressure effects of apomorphine and domperidone in parkinsonism. In: Yahr MD, Bergmann KJ, eds. Advances in neurology. New York: Raven Press, 1986: 263-66. 6. Hughes AJ, Lees AJ, Stem GM. Apomorphine test to predict dopaminergic responsiveness in parkinsonian syndromes. Lancet 1990; 356: 32-34.
