Pallidal vs subthalamic nucleus deep brain stimulation in Parkinson disease.

Background: Deep brain stimulation (DBS) of the globus pallidus interna (GPi) and subthalamic nucleus (STN) has been reported to relieve motor symptoms and levodopa-induced dyskinesia in patients with advanced Parkinson disease (PD). Although it has been suggested that stimulation of the STN may be superior to stimulation of the GPi, comparative trials are limited.

Objective: To extend our randomized, blinded pilot comparison of the safety and efficacy of STN and GPi stimulation in patients with advanced PD.

Pramipexole vs levodopa as initial treatment for Parkinson disease: a 4-year randomized controlled trial.

Background: The best way to initiate dopaminergic therapy for early Parkinson disease remains unclear.

Objective: To compare initial treatment with pramipexole vs levodopa in early Parkinson disease, followed by levodopa supplementation, with respect to the development of dopaminergic motor complications, other adverse events, and functional and quality-of-life outcomes.

Design: Multicenter, parallel-group, double-blind, randomized controlled trial.

Parkinson's disease: surgical options.

The introduction of levodopa revolutionized the treatment of Parkinson's disease. However, complications of therapy that diminish functional capacity eventually develop in the majority of patients. Studies in animal models have demonstrated that the parkinsonian state is associated with overactivity in the output nuclei of the basal ganglia.

Interactions between deep brain stimulation and levodopa in Parkinson's disease.

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 this has not been objectively measured. Further, the means by which DBS alters the response to levodopa to improve motor fluctuations is unknown.

Networks mediating the clinical effects of pallidal brain stimulation for Parkinson's disease: a PET study of resting-state glucose metabolism.

Employing [(18)F]fluorodeoxyglucose (FDG) and PET, we have found previously that stereotaxic ablation of the internal globus pallidus (GPi) for Parkinson's disease causes resting metabolic changes in brain regions remote from the lesion site. In this study we determined whether similar metabolic changes occur in Parkinson's disease patients treated with deep brain stimulation (DBS) of the GPi. We studied seven Parkinson's disease patients with FDG-PET to measure resting regional cerebral glucose utilization on and off GPi stimulation.

DBS and diathermy interaction induces severe CNS damage.

Pulse-modulated radiofrequency diathermy treatment to the maxilla produced permanent diencephalic and brainstem lesions and a vegetative state in a patient with PD with implanted subthalamic electrodes for deep brain stimulation.

Assessments of axial motor control during deep brain stimulation in parkinsonian patients.

Objective: We tested the hypothesis that bilateral deep brain stimulation (DBS) in the globus pallidus internus or the subthalamic nucleus improves various components of postural and oromotor function and that some of the components correlate with changes in the Unified Parkinson's Disease Rating Scale (UPDRS) in patients with Parkinson's disease.

Methods: Six patients with Parkinson's disease were evaluated for four postural and two orofacial UPDRS items, and quantitative tests of posture adjustments and oromotor control were performed while the patients were on and off DBS. Measurements of postural adjustments included reactive force and latency before a voluntary step.

Functional correlates of pallidal stimulation for Parkinson's disease.

We measured regional cerebral blood flow with H2 15O and positron emission tomography (PET) scanning at rest and during a motor task to study the mechanism of motor improvement induced by deep brain stimulation of the internal globus pallidus in Parkinson's disease. Six right-handed patients with Parkinson's disease were scanned while performing a predictable paced sequence of reaching movements and while observing the same screen displays and tones. PET studies were performed ON and OFF stimulation in a medication-free state.

A randomized, controlled trial of remacemide for motor fluctuations in Parkinson's disease.

Background: Preclinical studies suggest that glutamate antagonists help ameliorate motor fluctuations in patients with PD treated with levodopa.

Methods: In a multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study, the authors assessed the safety, tolerability, and efficacy of the glutamate receptor blocker remacemide hydrochloride in 279 patients with motor fluctuations treated with levodopa. The primary objective was to assess the short-term tolerability and safety of four dosage levels of remacemide during 7 weeks of treatment.

Outcome of unilateral and bilateral pallidotomy for Parkinson's disease: patient assessment.

Objective: Pallidotomy has recently regained acceptance as a safe and effective treatment for Parkinson's disease symptoms. The goal of this study was to obtain the patients' perspective on their results after undergoing this procedure. Special attention was focused on the potential complications and the respective advantages and risks of unilateral versus bilateral pallidotomy.

Comparison of pallidal and subthalamic nucleus deep brain stimulation for advanced Parkinson's disease: results of a randomized, blinded pilot study.

Objective: Deep brain stimulation (DBS) of the globus pallidus internus (GPi) and subthalamic nucleus (STN) has been reported to be effective in alleviating the symptoms of advanced Parkinson's disease (PD). Although recent studies suggest that STN stimulation may be superior to GPi stimulation, a randomized, blinded comparison has not been reported. The present study was designed to provide a preliminary comparison of the safety and efficacy of DBS at either site.

Ropinirole for the treatment of early Parkinson disease: a 12-month experience. Ropinirole Study Group.

Objective: To evaluate ropinirole hydrochloride as dopaminergic monotherapy in patients with early Parkinson disease.

Design: A 6-month extension of a double-blind, placebo-controlled study.

Setting: Ambulatory care at 22 different sites in the United States.

Ropinirole for the treatment of early Parkinson's disease. The Ropinirole Study Group.

A prospective, randomized, placebo-controlled, double-blind, parallel-group, 6-month study assessed the efficacy and safety of ropinirole, a nonergoline D2-dopamine agonist, in patients with early Parkinson's disease (n = 241; Hoehn & Yahr stages I to III) with limited or no prior dopaminergic therapy. Patients (mean age, 62.8 years), stratified by concomitant use of selegiline, were randomized to ropinirole (n = 116) or placebo (n = 125).

Solution structure of reduced plastocyanin from the blue-green alga Anabaena variabilis.

The three-dimensional solution structure of plastocyanin from Anabaena variabilis (A.v.PCu) has been determined by nuclear magnetic resonance spectroscopy.

Jaw movement dysfunction related to Parkinson's disease and partially modified by levodopa.

Objectives: To test the hypotheses that Parkinson's disease can differentially produce deficits in voluntary and rhythmic jaw movements, which involve different neuronal circuits, and that levodopa treatment improves specific components of the motor deficit.

Methods: Patients with idiopathic Parkinson's disease and control subjects were tested on a series of jaw motor tasks that included simple voluntary movement, isometric clenching, and natural and paced rhythmic movements. Jaw movements were measured by changes in electromagnetic fields and EMG activity.

Patterns of asymmetry do not change over the course of idiopathic parkinsonism: implications for pathogenesis.

We investigated the asymmetry of focal deficits of bradykinesia in a cross-sectional study of 198 patients with idiopathic parkinsonism. We have analyzed the difference in Unified Parkinson's Disease Rating Scale (UPDRS) scores between the more and less affected sides in these patients, whose duration of symptoms ranged from 1 to 15 years. There was no significant change in the asymmetry or focality over this period; the deficit for each side progressed faster initially and then approached the normal age-related linear rate of decline.

Controlled release levodopa/carbidopa 25/100 (Sinemet CR 25/100): pharmacokinetics and clinical efficacy in untreated parkinsonian patients.

The pharmacokinetics of the clinically determined optimal dose of controlled release levodopa/carbidopa 25/100 (Sinemet CR 25/100) after 12 weeks of therapy was studied in nine parkinsonian patients without prior exposure to levodopa. The pharmacokinetics of single oral doses of controlled release levodopa/carbidopa 25/100 and 50/200 were also compared. As predicted from the plasma half-life (1.

Clinical observations on the rate of progression of idiopathic parkinsonism.

The time course of evolution of clinical deficits has been a traditional guide to the nature of the aetiopathogenesis of neurological disease. We studied the influence of ageing and duration of disease on the natural history of idiopathic parkinsonism (IP). Two hundred and thirty-eight patients with IP were examined while off medication.

Effect of peripheral catechol-O-methyltransferase inhibition on the pharmacokinetics and pharmacodynamics of levodopa in parkinsonian patients.

Catechol-O-methyltransferase (COMT) metabolizes a portion of administered levodopa and thus makes it unavailable for conversion to dopamine in the brain. In an open-label trail, we examined the effects of entacapone, a peripheral inhibitor of COMT, administered acutely or for 8 weeks, on the pharmacokinetics and pharmacodynamics of levodopa in 15 parkinsonian subjects with a fluctuating response to levodopa. Acutely and chronically administered entacapone similarly decreased the plasma elimination of orally and intravenously administered levodopa.

Dihydroergotamine nasal spray for the acute treatment of migraine.

We conducted a multicenter, double-blind, parallel-group study to compare the efficacy and safety of dihydroergotamine (DHE) nasal spray and placebo over 4 hours in the treatment of migraine. Of the 112 patients enrolled, 100 were included in the "intent-to-treat" efficacy analysis. The patients self-administered either 2.

Tendon jerks in Parkinson's disease.

Tendon reflexes were examined in 119 patients with idiopathic parkinsonism (IP) and 40 spouse controls to estimate the type and frequency of any alterations in the reflexes. Forty one of 119 patients and 2 of 40 controls had reflex ratings of 3+ at two or more sites (p < 0.001).

The transport of L-6-fluorodopa and its metabolites from blood to cerebrospinal fluid and brain.

The transport of L-6-fluorodopa and its major metabolites from the blood to the brain, cerebrospinal fluid (CSF), and muscle was studied in carbidopa-pretreated cynomolgus monkeys. A bolus intravenous injection of 18F-L-6-fluorodopa was followed by serial positron emission tomography scans and sampling of cisternal CSF and arterial blood. The relative concentrations of L-6-fluorodopa and its metabolites were determined in blood plasma and CSF by high-performance liquid chromatography.

Does tolerance develop to levodopa? Comparison of 2- and 21-H levodopa infusions.

To determine if acute tolerance to levodopa develops, we compared the response to 2- and 21-h levodopa infusions with the rate adjusted during the long infusion to yield the same plasma concentration as at the end of the 2-h infusion. The duration of response after discontinuing the long infusions was briefer than after discontinuing the short infusion, suggesting the development of tolerance. Furthermore, dyskinesia severity was greater during long infusions.