Abstract
Marked fluctuations in mobility, known as the on-off phenomenon, frequently emerge during the course of chronic treatment with levodopa in patients with Parkinson's disease. Similar fluctuations in mobility and mental status have been observed in a 10-year-old Japanese girl with tetrahydrobiopterin deficiency (BH4 deficiency) while receiving neurotransmitter and biopterin supplement. In order to define the underlying mechanisms for the phenomenon in our patient, we studied the temporal relationship between plasma levodopa levels and clinical status during oral (2.0 mg/kg per day) and continuous intravenous (2.0 mg/kg per 12 h) administration of the drug. Following each oral levodopa dose, the plasma concentration of levodopa peaked at 60–90 ng/ml within 60 min and fell to 5–15 ng/ml within 2 h. The clinical state of the patient varied acutely in parallel with the plasma levodopa concentrations. The clinical swings completely disappeared when the plasma levodopa concentrations were stabilized between 120–150 ng/ml by continuous infusion. Paradoxically, on awakening from sleep, she was invariably ambulatory despite very low plasma levodopa levels (<10 ng/ml). These observations indicate that the on-off phenomenon in our patient reflect the fluctuations of plasma levodopa levels as demonstrated in Parkinson's disease, but there may be substantial differences in levodopa transport across the blood-brain barrier and/or striatal dopamine-receptor interaction between Parkinson's disease and BH4 deficiency.
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Abbreviations
- BH4 :
-
tetrahydrobiopterin
References
Agid Y, Agid FJ, Ruberg M (1987) Biochemistry of neurotrasmitters in Parkinsons's disease. In: Marsden CD, Fahn S (eds) Movement disorders 2. Butterworths, London, pp 166–230
Chase TN, Juncos J, Seratti C, Fabbrini G, Bruno G (1986) Fluctuation in response to chronic levodopa therapy: pathogenic and therapeutic considerations. Adv Neurol 45:477–480
Fahn S (1982) Fluctuation of dsability in Parkinson's disease: pathophysiology. In: Marsden CD, Fahn S (eds) Movement disorders. Butterworths, London, pp 123–145
Hansson C, Agrup G, Rorsman H, Rosengren AM, Rosengren E (1979) Analysis of cystenyldopas, dopa, dopamine, noradrenaline and adrenaline in serum and urine using high-performance liquid chromatography and electrochemical detection. J Chromatogr 162:7–22
Hardie R, Lees AJ, Stern GM (1986) Pharmacokinetics of levodopa and motor fluctuations. Adv Neurol 45:487–492
Hornykiewicz O, Kish SJ (1986) Biochemical pathophysiology of Parkinson's disease. Adv Neurol 45:19–34
Sweet RD, McDowell FH (1974) Plasma dopa concentrations and the “on-off” effect after chronic treatment of Parkinson's disease. Neurology 24:953–956
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Tanaka, Y., Matsuo, N., Tsuzaki, S. et al. On-off phenomenon in a child with tetrahydrobiopterin deficiency due to 6-pyruvoyl tetrahydropterin synthase deficiency (BH4 deficiency). Eur J Pediatr 148, 450–452 (1989). https://doi.org/10.1007/BF00595911
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DOI: https://doi.org/10.1007/BF00595911