The management of fluctuations in motor function complicating advanced Parkinson's disease with continuously administered dopaminomimetics was studied in 12 patients. In response to 7 to 12 days of round-the-clock intravenous infusions of levodopa, fluctuations in motor performance gradually diminished, ultimately by more than 40%. The beneficial effect persisted for about 6 days after withdrawal of continuous parenteral treatment and resumption of standard oral therapy. Clinical improvement was associated with changes in several pharmacological indices: Acute dose-response studies of intravenous levodopa showed a shift of the curve to the right in the immediate postinfusion phase compared to preinfusion studies; the therapeutic index improved significantly as patients demonstrated about 76% increased beneficial antiparkinsonian response with an equal degree of toxic dyskinetic effects; and the duration of action of levodopa was prolonged by 30%. These results suggest that changes in central dopaminergic mechanisms contributing to motor complications in advanced Parkinson's disease can be modified by procedures that provide continuous dopamine replacement. Presumably these modifications underlie the gradual amelioration of motor fluctuations over several days of round-the-clock therapy. Results of the present study also suggest potential deleterious effects of chronic intermittent oral treatment in the development of motor complications and thus support the role of long-term, continuous administration of dopaminomimetics.
Validation of the 12-item AST with the TULIA showed a remarkable diagnostic reliability with high specificity, sensitivity and positive predictive value, for the presence and severity of apraxia. The AST is shown to be a reliable and valid bedside test in patients with stroke, allowing a straightforward assessment of apraxia within a few minutes.
Patients with Parkinson's disease (PD) often show impaired manual dexterity even when being only minimally bradykinetic, suggesting that they may have limb kinetic apraxia (LKA), that is, a loss of fine motor skill not explained by elemental motor deficits. To explore this dissociation, we investigated the differential dopaminergic responsiveness of dexterity and bradykinesia in PD. Twelve patients with PD (4 women, age 64.4 +/- 8.3, mean + SD) and 12 matched healthy controls (64.8 +/- 8.9) were tested twice in ON vs. OFF and 1st vs. 2nd trial, respectively. A coin rotation (CR) task was applied to assess dexterity and a finger tapping (FT) task to assess bradykinesia. Performance was followed by video recording and analyzed by measuring the frequency of CR and FT during three 10-second periods. Statistical analysis was done by a mixed factorial design with group (PD vs. controls) as between-subject factor and medication (ON- vs. OFF-state or 1st vs. 2nd trial), task (FT vs. CR), and handedness (dominant vs. nondominant) as within-subject factors. In patients with PD, regardless of hand involved, dopaminergic treatment only mildly improved CR performance, in contrast to the strong increase in FT scores (up to the level of controls), as demonstrated by the significant triple interaction of the factors group, medication, and task (F(1,22) = 7.9, P = 0.01; eta(2) = 0.26). Furthermore, CR scores were considerably lower, both in OFF and ON, than in normal controls, pointing to a substantial impairment of dexterity in PD (P < 0.001). In conclusion, impaired manual dexterity showing significantly diminished response to dopaminergic treatment suggests that dextrous deficits in PD are related to LKA rather than bradykinesia.
Abnormal involuntary movements complicate the management of a majority of patients with advanced Parkinson's disease. The ability of levodopa to induce dyskinesias and alleviate parkinsonism has generally been considered a continuous dose-dependent pharmacological spectrum. In this study, the acute dose-response profile of intravenously administered levodopa for both inducing dyskinesia and alleviating parkinsonism, and its duration of action on these motor manifestations were evaluated in 52 parkinsonian patients. The minimum dose of levodopa required to produce mild dyskinetic movements was significantly lower in patients with fluctuations in motor response compared with those who had a stable response to standard oral therapy; the minimum dose for antiparkinsonian benefit, however, failed to show significant differences. The rate of disappearance of dyskinetic movements was faster than the rate of reappearance of parkinsonian signs following withdrawal of a steady-state infusion of levodopa. The dissociation of the pharmacodynamic profile of the two major motor effects of levodopa suggests their mediation through two different central pharmacological mechanisms, perhaps involving the two classes of dopamine receptors or other transmitter systems, and could have important implications for the design of future antiparkinsonian agents.
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