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OBJECTIVE To quantify the effects of deep brain stimulation (DBS) of globus pallidus interna (GPi) and subthalamic nucleus (STN) on motor fluctuations and dyskinesia in PD and to determine how the response to levodopa was modified by DBS. BACKGROUND Patients report that DBS reduces levodopa-induced motor fluctuations and dyskinesia throughout the day, but(More)
To determine whether tolerance to the antiparkinsonian actions of levodopa develops during longterm levodopa therapy, we compared the response to 2-hour levodopa infusions before and after 2- to 4-day levodopa holidays using tapping and walking speeds and tremor/dyskinesia scores as measures of response in 17 parkinsonian patients with a fluctuating(More)
The cause of motor fluctuations occurring during constant-rate levodopa infusions is unknown. We examined whether known pharmacokinetic factors could explain the fluctuations and looked for clues to pharmacodynamic causes. Eleven subjects with stage III-V Parkinson's disease (PD) and a fluctuating response to levodopa underwent constant-rate infusions for(More)
We examined the response to 2-hour levodopa infusions in 18 Parkinson's disease subjects before starting long-term levodopa treatment and after 6 and 12 months of treatment using tapping speed as an index of bradykinesia. The long-duration response (LDR), measured as the increase in baseline (overnight without levodopa) tapping speed, increased by 29 +/- 18(More)
The short-duration response, long-duration response, and dyskinetic response to levodopa change during long-term levodopa therapy. How these responses evolve, and which changes contribute to the emergence of motor fluctuations, remain unclear. We studied 18 subjects with Parkinson's disease before they began levodopa therapy and after 6, 12, 24, and 48(More)
Pilot data on mood and anxiety changes in 15 Parkinson's disease patients with motor fluctuations are described based on ratings every 30 min for 5 h bracketing a 2-h constant-rate levodopa infusion. Robust mood and anxiety effects slightly preceded but temporally paralleled fluctuations in motor tapping scores. Research nurse ratings blind to patient(More)
The authors investigated the ability of daytime infusions of apomorphine, a D-1 and D-2 dopamine agonist, to sustain the long-duration response (LDR) in seven subjects with fluctuating PD in whom L-DOPA was discontinued for 3 days. Apomorphine maintained the LDR to the extent that it kept the subjects "on" during the day. This observation suggests that the(More)
We investigated the effect of levodopa on mood and anxiety in eight Parkinson's disease patients with motor fluctuations. Each patient received 0.0-, 0.5-, and 1.0-mg/kg/hr levodopa infusions in randomly assigned order under double-blind conditions on consecutive days. Mood elevation and anxiety reduction based on half-hourly patient rating and a(More)
BACKGROUND Dyskinesias are a frequent adverse effect of long-term levodopa therapy. The relative contribution of dopamine D(1) and D(2) receptor function to the pathophysiology of levodopa-induced dyskinesias remains a matter of controversy. OBJECTIVE To establish whether a selective D(1) dopamine agonist induces more or less dyskinesia than levodopa in(More)