Parkinson's treatment

OBJECTIVE: We tested the hypothesis that dopamine-dependent motor learning mechanism underlies the long-duration response to levodopa in Parkinson disease (PD) based on our studies in a mouse model. By data-mining the motor task performance in dominant and nondominant hands of the subjects in a double-blind randomized trial of levodopa therapy, the effects of activity and dopamine therapy were examined. METHODS: We data-mined the Earlier versus Later Levodopa Therapy in Parkinson's Disease (ELLDOPA) study published in 2005 and performed statistical analysis comparing the effects of levodopa and dominance of handedness over 42 weeks...

BACKGROUND: A systematic assessment of potential disease-modifying compounds for Parkinson's disease concluded that pioglitazone could hold promise for the treatment of patients with this disease. We assessed the effect of pioglitazone on the progression of Parkinson's disease in a multicentre, double-blind, placebo-controlled, futility clinical trial. METHODS: Participants with the diagnosis of early Parkinson's disease on a stable regimen of 1 mg/day rasagiline or 10 mg/day selegiline were randomly assigned (1:1:1) to 15 mg/day pioglitazone, 45 mg/day pioglitazone, or placebo...

Psychotic symptoms occur in up to 40% of patients with Parkinson's disease (PD). Clozapine and quetiapine, two atypical antipsychotic drugs, at doses markedly lower than those effective in schizophrenia, which, nevertheless, still cause sedation, hypotension, and other side effects, are widely used to treat psychotic symptoms in patients with PD psychosis (PDP), although quetiapine has never been shown to be effective in a placebo-controlled study. The demonstrated efficacy of clozapine in PDP has been attributed to serotonin (5-HT(2A)) receptor blockade...

We have shown that routine biopsies of the ascending colon obtained at colonoscopy allow the detection of Lewy neurites (LN) in the enteric nervous system (ENS) of Parkinson's disease (PD) patients. Although colonoscopy is a relatively safe procedure, it requires colon preparation and anesthesia. The present study was therefore undertaken to evaluate whether descending colon and rectal biopsies that are obtainable by rectosigmoidoscopy allow the detection of Lewy pathology in the ENS. A total of 9 controls and 26 PD patients were included and analyzed...

Loss of dopaminergic neurons from the substantia nigra characterizes the classical pathology of Parkinson's disease, but persistent activation of N-methyl-D-aspartate receptors is also a major component. During difficult airway management in a patient with advanced Parkinson's disease, the use of low-dose (20 mg) i.v. ketamine resulted in complete abolition of severe tremor and dysarthria. This led to the current case report in which low-dose ketamine was used for preoperative sedation and dyskinesia attenuation...

Rasagiline is an irreversible monoamine oxidase type B (MAO-B) inhibitor indicated for the treatment of the signs and symptoms of idiopathic Parkinson disease as initial monotherapy and as adjunct therapy to levodopa. Pharmacologic inhibition of monoamine oxidase type A (MAO-A), but not MAO-B, poses a risk of the "cheese effect," a hypertensive response to excess dietary tyramine, a biogenic sympathomimetic amine. Tyramine challenge studies, conducted to characterize rasagiline selectivity for the MAO-B enzyme and tyramine sensitivity, demonstrate that rasagiline, when used at the recommended dose, is selective for MAO-B and is not associated with heightened tyramine sensitivity...

OBJECTIVE: To evaluate the association between diagnosis of Parkinson disease (PD) and risk factors or early symptoms amenable to population-based screening. METHODS: A systematic review and meta-analysis of risk factors for PD. RESULTS: The strongest associations with later diagnosis of PD were found for having a first-degree or any relative with PD (odds ratio [OR], 3.23; 95% confidence interval [CI], 2.65-3.93 and OR, 4.45; 95% CI, 3.39-5...

OBJECTIVE: To assess whether risk factors for Parkinson disease and dementia with Lewy bodies increase rate of defined neurodegenerative disease in idiopathic rapid eye movement (REM) sleep behavior disorder (RBD). METHODS: Twelve centers administered a detailed questionnaire assessing risk factors for neurodegenerative synucleinopathy to patients with idiopathic RBD. Variables included demographics, lifestyle factors, pesticide exposures, occupation, comorbid conditions, medication use, family history, and autonomic/motor symptoms...

STUDY OBJECTIVES: To investigate the capacity of neuropsychological deficits in idiopathic rapid eye movement sleep behavior disorder (iRBD) to predict the development of dementia and/or parkinsonism. DESIGN: Prospective longitudinal follow-up study. SETTING: Tertiary sleep center. PATIENTS: Twenty patients with initial iRBD (19 males, mean age 66.1 ± 7.1) underwent a clinical and neuropsychological follow-up within a mean of 43 ± 19 months...

IMPORTANCE: Little is known about the relative contributions of multisystem degenerative processes across the spectrum of predemented cognitive decline in Parkinson disease (PD). OBJECTIVE: To investigate the relative frequency of caudate nucleus dopaminergic and forebrain cholinergic deficits across a spectrum of cognitively impaired patients with PD to explore their relative, individual, and combined contributions to cognitive impairment in PD. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study at an academic movement disorders clinic that included a predominantly nondemented cohort of 143 patients with PD...

BACKGROUND AND PURPOSE: Deep brain stimulation (DBS) for severe Parkinson's disease (PD) outperforms the best medical treatment in controlling motor symptoms and improving quality of life. Nevertheless disease progression cannot be controlled, and the development of dementia over time is nearly inevitable, often resulting in nursing home placement. Ten-year survival, development of hallucinations, dementia and nursing home placement were examined and adverse events were assessed. METHOD: Patient files were scrutinized from baseline up to 10 years of treatment or death on all 79 PD patients treated with DBS of the subthalamic nucleus from 1998 to 2003 at Aarhus University Hospital...

Since brain stem regions associated with early Parkinson's disease (PD) pathology encroach upon those involved in taste function, the ability to taste may be compromised in PD. However, studies on this point have been contradictory. We administered well-validated whole-mouth and regional taste tests that incorporated multiple concentrations of sucrose, citric acid, caffeine, and sodium chloride to 29 early stage PD patients and 29 age-, sex-, and race-matched controls. Electrogustometry was also performed on the anterior tongue...

BACKGROUND AND PURPOSE: Cerebral microbleeds (CMBs) have been extensively studied in healthy controls and patients with cerebrovascular disease and Alzheimer's disease. Our aim was to characterize the clinical and radiological features of CMBs in idiopathic Parkinson's disease (IPD). METHODS: This cross-sectional study included consecutive parkinsonian patients who attended the authors' movement disorders clinic from March 2010 to February 2012 and underwent a standard magnetic resonance imaging (MRI) protocol with gradient recalled echo taken with a 3 T MRI machine...

BACKGROUND: In models of dopaminergic neuronal loss, the dopamine agonist pramipexole has exhibited neuroprotective properties. The Pramipexole On Underlying Disease (PROUD) study was designed to identify whether early versus delayed pramipexole initiation has clinical and neuroimaging benefits in patients with Parkinson's disease (PD). METHODS: Between May 24, 2006, and April 22, 2009, at 98 centres, we recruited patients with PD diagnosed within 2 years and aged 30-79 years...

Freezing of gait (FOG) is a disabling motor symptom experienced by a large proportion of patients with Parkinson's disease (PD). While it is known that FOG contributes to lower health-related quality of life (HRQoL), previous studies have not accounted for other important factors when measuring the specific impact of this symptom. The aim of this study was to examine FOG and HRQoL while controlling for other factors that are known to impact patient well-being, including cognition, motor severity, sleep disturbance and mood...

IMPORTANCE: Symptoms in the genital region, such as pain, discomfort, tingling, and burning sensations, have rarely been reported in Parkinson disease (PD), and the previous cases were attributed to nonmotor off symptoms. We report a patient with PD and severe genital discomfort unrelated to motor fluctuations but compatible with restless genital syndrome. OBSERVATIONS: A 65-year-old woman with PD experienced a disabling discomfort in her pelvis and genital region for 3 years...

Apathy is a behavioural disturbance occurring alone or in concomitance with depression in Parkinson's disease (PD). Here we present a validation study for the self-report version of the Apathy Evaluation Scale (AES-S), carried out in a sample of 60 non-demented, non-depressed untreated, drug-naïve, de novo PD patients; 20 patients of the sample (33.3%) were classified as apathetic according to current clinical criteria. All enrolled patients completed the AES-S and a neurological and cognitive assessment. Mean AES-S score was 34...

In this study, we investigated the effect of dopaminergic medication on reactive stepping responses to forward and backward balance perturbations in patients with moderately severe Parkinson's disease (PD). Twelve PD patients, Hoehn and Yahr stage ranging from 2 to 3, and 15 healthy controls were exposed to multidirectional translational stance perturbations on a moveable platform. Perturbations were unpredictable in terms of amplitude, timing and direction. Patients were tested in the medication ON and OFF (at least 12 h of dopaminergic medication withdrawal) state on two separate days...

OBJECTIVE: To assess whether being able to quit smoking is an early marker of Parkinson disease (PD) onset rather than tobacco being "neuroprotective," we analyzed information about ease of quitting and nicotine substitute use. METHODS: For this case-control study, we identified 1,808 patients with PD diagnosed between 1996 and 2009 from Danish registries, matched 1,876 population controls on sex and year of birth, and collected lifestyle information. We estimated odds ratios and 95% confidence intervals with logistic regression adjusting for matching factors and confounders...

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