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We studied the temporal patterns of chorea and plasma levodopa profiles in 30 patients with Parkinson's disease whose motor fluctuations were difficult to characterize and treat on the basis of observation alone. We were able to determine whether chorea was associated with high levodopa concentrations or low levodopa concentrations or both. We found the following patterns of levodopa-associated chorea: chorea due to inadequate levodopa levels, chorea due to biphasic levodopa absorption, chorea associated with either rapid or slow levodopa absorption, and chorea due to long-duration levodopa absorption mimicking a sustained-release preparation. Seven patients benefited after their dosing schedules were rearranged as a result of information gained from monitoring. We conclude that any patient with levodopa-associated chorea who cannot be regulated on the basis of observation alone should be studied with simultaneous plasma levodopa measurements and clinical monitoring to detect an unusual plasma levodopa pattern that may be improved by adjustment of dosing schedule.

We report the clinical spectrum of 3 patients with Parkinson's disease who experienced complex patterns of levodopa-related dystonia. Dystonia was unrelieved by multiple medication regimens but responded well to continuous, duodenal levodopa infusions. Patients were able to remain mobile without severe dystonia despite a very narrow window of benefit between the levodopa concentration necessary to achieve the "on" state and that which caused the onset of dystonic spasms.

Buspirone, an azospirone compound, is a nonsedative anxiolytic that has achieved wide usage since its introduction in 1987. Although relatively free of side-effects, there have been several instances of dyskinesia and dystonia associated with the use of buspirone. We report two patients with persistent movement disorders that developed after prolonged treatment with the drug. One patient developed a lasting problem of cervical-cranial dystonia and tremors after treatment with buspirone at a dosage of 40 mg/day for several weeks. Another, receiving 30 mg/day for 6 weeks, experienced an exacerbation of preexisting spasmodic torticollis and tardive dyskinesia as well as the onset of involuntary phonations. As shown by these and other examples, buspirone poses the risk for inducing or exacerbating several types of movement disorders.

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Recently we reported that the rate of protein breakdown decreases during development. Breakdown rates were calculated from the rates of protein synthesis and the changes in brain protein content with age. A different study, measuring breakdown by monitoring the loss of label from brain protein after an H14CO3- pulse, came to the opposite conclusion: that the rate of breakdown is low in immature brain and increases during development. We have now investigated some of the factors (the distribution of label in protein and the potential for recycling) that might introduce errors into these measurements. The specific radioactivities of both protein-bound and free amino acids were determined in the brains of young rats several days after an intraperitoneal pulse of H14CO3-. For a number of amino acids the specific radioactivity of the free amino acid is high compared with that of the protein-bound amino acid, and therefore recycling could result in an underestimate of the degradation rate. Because glutamic acid had a relatively low specific-radioactivity ratio, [1-14C]glutamic acid was used in a pulse-labelling experiment to measure degradation. The rate so obtained, 0.6% . h-1, is twice the rate found with H14CO3- labelling (based on total protein-bound radioactivity). Insofar as recycling is a possible complication, 0.6% . h-1 may be a minimum value. Although somewhat higher degradation rates are found after labelling with an intracranial pulse, which was considered as a possible route to limit recycling, there are difficulties in interpreting these data.

Ten patients with Parkinson’s disease and severe motor fluctuations were given Sinemet (25/100) for 4 weeks followed by 4 weeks of Sinemet (CR-4). After each drug preparation was optimized, patients were rated by neurological examination and plasma levodopa (LD) measured at hourly intervals (9 a.m.-4 p.m.). For the group as a whole, variations throughout the day of plasma LD and clinical state were no different on the 2 formulations. Three patients whose fluctuations responded well to CR-4 had either much less variable plasma LD levels on CR-4 or were able to maintain plasma LD above a minimum threshold. In severe fluctuators, a major benefit from CR-4 can be expected only in those patients who can maintain steady plasma LD levels above the threshold for achieving the ‘on’ state.

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