189
arterial hypotension. SVT was treated by intravenous adenosine, with a dose schedule of 50 Lg/kg body weight increasing in 50 ug increments at 2 min intervals to a total of 250 pg/kg body weight, with no benefit. Each dose of adenosine resulted in a decreased mean intra-arterial pressure (MAP) and an associated rise in ICP, which was dose related. The initial ICP was 15-20 cm CSF, rising to 30-35 cm CSF with a dose of 150 ltg/kg, and 40 cm CSF with 250 g/kg. On each occasion the rise in ICP lasted about 2 min and returned to the baseline value with no further treatment. The dysrhythmia was not corrected by verapamil subsequently, but was successfully ended with direct current counter shock. It was noted that verapamil substantially lowered MAP but did not raise ICP. This case suggests that intravenous adenosine raises ICP and that caution should be used in patients in whom ICP is already high. Departments of Medicine and Intensive Care Unit,
K. W. CLARKE S. G. BREAR S. P. HANLEY
North Manchester General Hospital, Manchester M8 6RB, UK
1. Sollevi A, Ericson K, Enksson L, Lindqvist C, Langerkranse M, Stone-Elander S. Effect of adenosine of human cerebral blood flow as determined by positron emission tomography. J Cereb Blood Flow Metab 1987; 7: 673-78.
Our concern,
therefore, should
not
be directed towards the
"cytotoxic" effects of long-term levodopa but to the restoration of normal synaptic dopamine function. There is ample evidence that peripheral pharmacokinetic factors contribute to the complex response to levodopa,’’ notably the erratic and slowed gastric emptying that emerges after long-term use. Other limitations on the availability of levodopa for the brain are inefficient absorption from the small intestine, variable peripheral metabolism, and competition with large neutral aminoacids for transport across the blood-brain barrier. In contrast to 3-0-methyldopa, levodopa is not stored in
muscle,’O
so
muscle
cannot
contribute
to
the continuous
availability of levodopa. A harmful effect of long-term levodopa cannot explain fluctuations in motor performance, and levodopa should be introduced at the earliest opportunity. Department of Neurology, University Hospital, B-1090 Brussels, Belgium
DIRK DELEU
1. Yahr MD, Wolf A, Antunes JL,
parkinsonism following
treatment
Miyoshi K, Duffy P. Autopsy findings m with levodopa Neurology 1970; 6 (suppl 1):
55-66.
Quinn N, Parkes JD, Janota I, Marsden CD. Preservation of substantia nigra and locus coeruleus in a patient receiving levodopa (2 kg) plus decarboxylase inhibitor over a four-year period. Mov Disord 1986; 1: 65-68. 3. Bergman KJ, Mendoza MR, Yahr MD. Parkinson’s disease and long-term levodopa therapy Adv Neurol 1986, 45: 463-67 4. Caracem T, Scigliano G, Musicco M. The occurrence of motor fluctuations in parkinsonian patients treated long term with levodopa. role of early treatment and disease progression. Neurology 1991; 41: 380-84. 5. Deleu D, Ebinger G, Michotte Y. A clinical and pharmacokinetic comparison of oral and duodenal delivery of levodopa/carbidopa in patients with Parkinson’s disease with fluctuating responses to levodopa. Eur J Clin Pharmacol 1991; 41: 453-58. 6. Nutt JG. On-off phenomenon: relation to levodopa pharmacokinetics and pharmacodynamics. Ann Neurol 1987; 22: 535-40 7. Langston JW, Ballard P Parkinsonism induced by 1-methyl-4-phenyl-1-2,3,6tetrahydropyridine (MPTP): implications for treatment and the pathogenesis of Parkinson’s disease. Can JNeurol Sci 1984; 11 (suppl): 160-65. 8. Markham CH. The choreoathetoid movement disorder induced by levodopa. Clin 2.
Infantile spasms SIR,-Dr Rosenthal and Dr Belhnan (Dec 24, p 1532) are 100 years out in ascribing the first record of infantile spasms in The Lancet as having been made 50 years ago. In 1841 West’ wrote that inhis own son at 4 months of age "I first observed slight bobbings of the head forward, which I then regarded as a trick, but were in fact, the first indications of the disease; for these bobbings increased in frequency, and at length became so frequent and powerful, as to cause a complete heaving of the head forward towards his knees, and then immediately relaxing into the upright position". I have lately seen a 1-year-old whose articulate mother gave a strikingly similar description of seizures at 7 months of age. When she mentioned this to a medical practitioner she was told that "babies do these sort of things". The child has tuberous sclerosis. I wish to emphasise the repetitive nature of the spasms and suggest that any child who has repeated stereotyped movements should be referred for specialist opinion.
Department of Paediatric Neurology, Hospital for Sick Children,
LINDSAY J. SMITH
London WC1, UK
1 West WJ. On a peculiar form of infantile convulsions
Lancet 1841; i 724-25.
Levodopa SIR,-Dr Arts and colleagues (Nov 9, p 1210) conclude that levodopa had no harmful effect in non-parkinsonian patients. This is not surprising: neither in laboratory animals nor in parkinsonian patients’ is there pathological evidence to support the hypothesis that long-term levodopa administration induces degeneration of pigmented dopaminergic neurons of the substantia nigra or accelerates the progression of Parkinson’s disease. Loss of dopaminergic neurons, not the duration of levodopa treatment, is the key factor in the emergence of fluctuations in motor performance. These fluctuations are more commonly observed in patients with advanced disease, in whom delayed initiation of levodopa therapy not only increases the likelihood of dyskinesia33 and other response fluctuations4 but also shortens the latency at which they appear after treatment begins. Secondly, there is a good correlation between plasma levodopa concentrations and clinical status in advanced Parkinson’s disease.s Thirdly, the nervous system of patients with motor response fluctuations retains the capacity to respond clinically to levodopa.6 Fourthly, Langston and Ballard’ observed response fluctuations within a few months of instituting levodopa therapy in several patients with parkinsonism due to 1-methyl-4-phenyl-1-2,3,6-tetrahydropyridine exposure, a chemical which destroys selectively the pigmented dopaminergic cells of the substantia nigra. Finally, Markham8 noted that dyskinesias were occurring in the most symptomatic limbs in patients with Parkinson’s disease, basically corresponding to those areas with prominent dopaminergic cell loss.
Pharmacol Ther 1971; 12: 340-43. 9 Nutt JG, Fellman JH. Pharmacokinetics of levodopa. Clin Neuropharmacol 1984, 7: 35-49. 10. Deleu D, Sarre S, Ebinger G, Michotte Y. In vivo pharmacokinetics of levodopa and 3-O-methyldopa in muscle: a microdialysis study. Naunyn-Schmiedeberg’s Arch
Pharmacol 1991; 344: 514-19.
Social
care
of children born to HIV-infected
parents SIR,-More than 95 % of children reported to the Italian register of paediatric HIV infection are born to HIV-positive mothers, most of whom are intravenous drug users (IVDU).’ About 15% of these infants are infected by HIV.2 Uninfected children are, however, also affected by their parents’ disease. A large proportion of these children will be orphaned before they are 10 years old. Moreover, many are born into socially disadvantaged families in which one or both parents are often IVDUs. Some babies are abandoned just after delivery and many are affected by the drug use of their parents; HIV infection is just one aspect of that. In Padova, from 1984, 177 children born to HIV-positive mothers were followed from birth according to a standard protocol. About 80% of the mothers had a history of IVDU and an additional 12% were sexual partners of drug users. Most parents were free of symptoms at the time of the birth. The figure shows the percentage of children living with at least one of their biological parents, estimated by survival analysis. 34 (19%) children were abandoned at birth or soon afterwards and were cared for by adoptive or foster parents. In addition, 20% of the remaining 143 children lost their parents before they were 6 years old, either because their parents died from AIDS or drug overdose, or because they were abandoned. No difference in the conditions of care between HIV infected and uninfected children was seen. Most (90%) of the orphaned children were living with other relatives, usually grandparents. In the absence of a cure for HIV infection an increasing number of children of HIV-positive mothers will not be living with their biological parents. If the characteristics of our cohort are representative, we can assume that in Italy over the next 2 years several hundred children
arterial hypotension. SVT was treated by intravenous adenosine, with a dose schedule of 50 Lg/kg body weight increasing in 50 ug increments at 2 min intervals to a total of 250 pg/kg body weight, with no benefit. Each dose of adenosine resulted in a decreased mean intra-arterial pressure (MAP) and an associated rise in ICP, which was dose related. The initial ICP was 15-20 cm CSF, rising to 30-35 cm CSF with a dose of 150 ltg/kg, and 40 cm CSF with 250 g/kg. On each occasion the rise in ICP lasted about 2 min and returned to the baseline value with no further treatment. The dysrhythmia was not corrected by verapamil subsequently, but was successfully ended with direct current counter shock. It was noted that verapamil substantially lowered MAP but did not raise ICP. This case suggests that intravenous adenosine raises ICP and that caution should be used in patients in whom ICP is already high. Departments of Medicine and Intensive Care Unit,
K. W. CLARKE S. G. BREAR S. P. HANLEY
North Manchester General Hospital, Manchester M8 6RB, UK
1. Sollevi A, Ericson K, Enksson L, Lindqvist C, Langerkranse M, Stone-Elander S. Effect of adenosine of human cerebral blood flow as determined by positron emission tomography. J Cereb Blood Flow Metab 1987; 7: 673-78.
Our concern,
therefore, should
not
be directed towards the
"cytotoxic" effects of long-term levodopa but to the restoration of normal synaptic dopamine function. There is ample evidence that peripheral pharmacokinetic factors contribute to the complex response to levodopa,’’ notably the erratic and slowed gastric emptying that emerges after long-term use. Other limitations on the availability of levodopa for the brain are inefficient absorption from the small intestine, variable peripheral metabolism, and competition with large neutral aminoacids for transport across the blood-brain barrier. In contrast to 3-0-methyldopa, levodopa is not stored in
muscle,’O
so
muscle
cannot
contribute
to
the continuous
availability of levodopa. A harmful effect of long-term levodopa cannot explain fluctuations in motor performance, and levodopa should be introduced at the earliest opportunity. Department of Neurology, University Hospital, B-1090 Brussels, Belgium
DIRK DELEU
1. Yahr MD, Wolf A, Antunes JL,
parkinsonism following
treatment
Miyoshi K, Duffy P. Autopsy findings m with levodopa Neurology 1970; 6 (suppl 1):
55-66.
Quinn N, Parkes JD, Janota I, Marsden CD. Preservation of substantia nigra and locus coeruleus in a patient receiving levodopa (2 kg) plus decarboxylase inhibitor over a four-year period. Mov Disord 1986; 1: 65-68. 3. Bergman KJ, Mendoza MR, Yahr MD. Parkinson’s disease and long-term levodopa therapy Adv Neurol 1986, 45: 463-67 4. Caracem T, Scigliano G, Musicco M. The occurrence of motor fluctuations in parkinsonian patients treated long term with levodopa. role of early treatment and disease progression. Neurology 1991; 41: 380-84. 5. Deleu D, Ebinger G, Michotte Y. A clinical and pharmacokinetic comparison of oral and duodenal delivery of levodopa/carbidopa in patients with Parkinson’s disease with fluctuating responses to levodopa. Eur J Clin Pharmacol 1991; 41: 453-58. 6. Nutt JG. On-off phenomenon: relation to levodopa pharmacokinetics and pharmacodynamics. Ann Neurol 1987; 22: 535-40 7. Langston JW, Ballard P Parkinsonism induced by 1-methyl-4-phenyl-1-2,3,6tetrahydropyridine (MPTP): implications for treatment and the pathogenesis of Parkinson’s disease. Can JNeurol Sci 1984; 11 (suppl): 160-65. 8. Markham CH. The choreoathetoid movement disorder induced by levodopa. Clin 2.
Infantile spasms SIR,-Dr Rosenthal and Dr Belhnan (Dec 24, p 1532) are 100 years out in ascribing the first record of infantile spasms in The Lancet as having been made 50 years ago. In 1841 West’ wrote that inhis own son at 4 months of age "I first observed slight bobbings of the head forward, which I then regarded as a trick, but were in fact, the first indications of the disease; for these bobbings increased in frequency, and at length became so frequent and powerful, as to cause a complete heaving of the head forward towards his knees, and then immediately relaxing into the upright position". I have lately seen a 1-year-old whose articulate mother gave a strikingly similar description of seizures at 7 months of age. When she mentioned this to a medical practitioner she was told that "babies do these sort of things". The child has tuberous sclerosis. I wish to emphasise the repetitive nature of the spasms and suggest that any child who has repeated stereotyped movements should be referred for specialist opinion.
Department of Paediatric Neurology, Hospital for Sick Children,
LINDSAY J. SMITH
London WC1, UK
1 West WJ. On a peculiar form of infantile convulsions
Lancet 1841; i 724-25.
Levodopa SIR,-Dr Arts and colleagues (Nov 9, p 1210) conclude that levodopa had no harmful effect in non-parkinsonian patients. This is not surprising: neither in laboratory animals nor in parkinsonian patients’ is there pathological evidence to support the hypothesis that long-term levodopa administration induces degeneration of pigmented dopaminergic neurons of the substantia nigra or accelerates the progression of Parkinson’s disease. Loss of dopaminergic neurons, not the duration of levodopa treatment, is the key factor in the emergence of fluctuations in motor performance. These fluctuations are more commonly observed in patients with advanced disease, in whom delayed initiation of levodopa therapy not only increases the likelihood of dyskinesia33 and other response fluctuations4 but also shortens the latency at which they appear after treatment begins. Secondly, there is a good correlation between plasma levodopa concentrations and clinical status in advanced Parkinson’s disease.s Thirdly, the nervous system of patients with motor response fluctuations retains the capacity to respond clinically to levodopa.6 Fourthly, Langston and Ballard’ observed response fluctuations within a few months of instituting levodopa therapy in several patients with parkinsonism due to 1-methyl-4-phenyl-1-2,3,6-tetrahydropyridine exposure, a chemical which destroys selectively the pigmented dopaminergic cells of the substantia nigra. Finally, Markham8 noted that dyskinesias were occurring in the most symptomatic limbs in patients with Parkinson’s disease, basically corresponding to those areas with prominent dopaminergic cell loss.
Pharmacol Ther 1971; 12: 340-43. 9 Nutt JG, Fellman JH. Pharmacokinetics of levodopa. Clin Neuropharmacol 1984, 7: 35-49. 10. Deleu D, Sarre S, Ebinger G, Michotte Y. In vivo pharmacokinetics of levodopa and 3-O-methyldopa in muscle: a microdialysis study. Naunyn-Schmiedeberg’s Arch
Pharmacol 1991; 344: 514-19.
Social
care
of children born to HIV-infected
parents SIR,-More than 95 % of children reported to the Italian register of paediatric HIV infection are born to HIV-positive mothers, most of whom are intravenous drug users (IVDU).’ About 15% of these infants are infected by HIV.2 Uninfected children are, however, also affected by their parents’ disease. A large proportion of these children will be orphaned before they are 10 years old. Moreover, many are born into socially disadvantaged families in which one or both parents are often IVDUs. Some babies are abandoned just after delivery and many are affected by the drug use of their parents; HIV infection is just one aspect of that. In Padova, from 1984, 177 children born to HIV-positive mothers were followed from birth according to a standard protocol. About 80% of the mothers had a history of IVDU and an additional 12% were sexual partners of drug users. Most parents were free of symptoms at the time of the birth. The figure shows the percentage of children living with at least one of their biological parents, estimated by survival analysis. 34 (19%) children were abandoned at birth or soon afterwards and were cared for by adoptive or foster parents. In addition, 20% of the remaining 143 children lost their parents before they were 6 years old, either because their parents died from AIDS or drug overdose, or because they were abandoned. No difference in the conditions of care between HIV infected and uninfected children was seen. Most (90%) of the orphaned children were living with other relatives, usually grandparents. In the absence of a cure for HIV infection an increasing number of children of HIV-positive mothers will not be living with their biological parents. If the characteristics of our cohort are representative, we can assume that in Italy over the next 2 years several hundred children
