We present a clinimetric assessment of the Movement Disorder Society (MDS)-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS). The MDS-UDPRS Task Force revised and expanded the UPDRS using recommendations from a published critique. The MDS-UPDRS has four parts, namely, I: Non-motor Experiences of Daily Living; II: Motor Experiences of Daily Living; III: Motor Examination; IV: Motor Complications. Twenty questions are completed by the patient/caregiver. Item-specific instructions and an appendix of complementary additional scales are provided. Movement disorder specialists and study coordinators administered the UPDRS (55 items) and MDS-UPDRS (65 items) to 877 English speaking (78% non-Latino Caucasian) patients with Parkinson's disease from 39 sites. We compared the two scales using correlative techniques and factor analysis. The MDS-UPDRS showed high internal consistency (Cronbach's alpha 5 0.79-0.93 across parts) and correlated with the original UPDRS (q 5 0.96). MDS-UPDRS acrosspart correlations ranged from 0.22 to 0.66. Reliable factor structures for each part were obtained (comparative fit index > 0.90 for each part), which support the use of sum scores for each part in preference to a total score of all parts. The combined clinimetric results of this study support the validity of the MDS-UPDRS for rating PD.2008 Movement Disorder Society

This article presents the revision process, major innovations, and clinimetric testing program for the Movement

No abstract

Background:The risk of Parkinson disease (PD) and its rate of progression may decline with increasing concentration of blood urate, a major antioxidant.Objective: To determine whether serum and cerebrospinal fluid concentrations of urate predict clinical progression in patients with PD.Design, Setting, and Participants: Eight hundred subjects with early PD enrolled in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) trial. The pretreatment urate concentration was measured in serum for 774 subjects and in cerebrospinal fluid for 713 subjects.Main Outcome Measures: Treatment-, age-, and sexadjusted hazard ratios (HRs) for clinical disability requiring levodopa therapy, the prespecified primary end point of the original DATATOP trial. Results:The HR of progressing to the primary end point decreased with increasing serum urate concentrations (HR for highest vs lowest quintile = 0.64; 95% confidence interval [CI], 0.44-0.94; HR for a 1-SD Author Affiliations are listed at the end of this article.

Oxidant-mediated damage is suspected to be involved in the pathogenesis of several neurodegenerative disorders . Iron promotes conversion of hydrogen peroxide to hydroxyl radical and, thus, may contribute to oxidant stress . We measured iron and its transport protein transferrin in caudate, putamen, globus pallidus, substantia nigra, and frontal cortex of subjects with Alzheimer's disease (n = 14) and Parkinson's disease (n = 14), and in younger adult (n = 8) and elderly (n = 8) normal controls . Although there were no differences between control groups with regard to concentrations of iron and transferrin, iron was significantly increased (p < 0 .05) in Alzheimer's disease globus pallidus and frontal cortex and Parkinson's disease globus pallidus, and transferrin was significantly increased in Alzheimer's disease frontal cortex, compared with elderly controls . The transferrin/ iron ratio, a measure of iron mobilization capacity, was decreased in globus pallidus and caudate in both disorders . Regional transferrin and iron concentrations were generally more highly correlated (Pearson's correlation coefficient) in elderly controls than in Alzheimer's and Parkinson's disease . The altered relationship between iron and transferrin provides further evidence that a disturbance in iron metabolism may be involved in both disorders .

The brain requires a ready supply of iron for normal neurological function, but free iron is toxic . Consequently, iron bioavailability must be stringently regulated . Recent evidence has suggested that the brain iron regulatory system is dysfunctional in neurological disorders such as Alzheimer's and Parkinson's diseases (AD and PD, respectively) . A key component of the iron regulatory system in the brain is ferritin . Ferritin consists of 24 subunits, which are distinguished as either a heavy-chain (H) or light-chain (L) isoform . These peptide subunits are genetically and functionally distinct . Thus, the ability to investigate separately the types of ferritin in brain should provide insight into iron management at both the cellular and the molecular level . In this study, the ratio of isoferritins was determined in select regions of adult elderly AD and PD human brains . The H-rich ferritin was more abundant in the young brain, except in the globus pallidus where the ratio of H/L ferritin was 1 :1 . The balance of H/ L isoferritins was influenced by age, brain region, and disease state . With normal aging, both H and L ferritin increased ; however, the age-associated increase in isoferritins generally failed to occur in AD and PD brain tissue . The imbalance in H/L isoferritins was disease and region specific . For example, in frontal cortex, there was a dramatic (fivefold) increase in the ratio of H/L ferritin in AD brains but not in PD brains . In PD, caudate and putamen H/L ratios were higher than in AD and the elderly control group . The analysis of isoferritin expression in brain provides insight into regional iron regulation under normal conditions and suggests a loss of ability to maintain iron homeostasis in the two disease states. This latter observation provides further evidence of dysfunction of iron homeostatic mechanisms in AD and PD and may contribute significantly to understanding the underlying pathogenesis of each, particularly in relation to iron-induced oxidative damage . Key Words : Neurological disorders-Oxidative damage-Iron-CNS-Basal ganglia . J. Neurochem. 65, 717-724 (1995) .Ferritin is the major iron storage protein and consists of different ratios of predominantly two isoforms . The

Objective: Based on new understanding of nondopaminergic pathways involved in Parkinson's disease (PD) pathophysiology, a selective adenosine A 2A receptor antagonist, istradefylline, shows promise for the treatment of PD. Methods: Istradefylline (40mg/day) was studied in levodopa-treated PD subjects experiencing prominent wearing-off motor fluctuations. At 23 North American sites, 196 subjects were randomized in a double-blind, 12-week outpatient clinical trial of istradefylline (114 completing the trial) or placebo (58 completing the trial). The primary efficacy measure was change from baseline to end point in the percentage of daily awake "off" time, recorded by subjects using a patient PD diary. Secondary end points evaluated "on" time (including "on time with dyskinesia"), the Unified Parkinson's Disease Rating Scale, and a Clinical Global Impression-Improvement of Illness score. Clinical laboratory, electrocardiograms, vital signs, and adverse event monitoring comprised the safety monitoring. Results: After randomization, approximately 88% of subjects completed the double-blind period. Compared with baseline, the decrease of daily awake "off" time for istradefylline was a mean (Ϯ standard deviation) of Ϫ10.8 Ϯ 16.6% (95% confidence interval, Ϫ13.46 to Ϫ7.52) and for placebo, Ϫ4.0 Ϯ 15.7% (95% confidence interval, Ϫ7.73-0.31; p ϭ 0.007 using two-way analysis of variance). This effect corresponded to changes from baseline in total daily awake "off" time of Ϫ1.8 Ϯ 2.8 hours for istradefylline and Ϫ0.6 Ϯ 2.7 hours for placebo ( p ϭ 0.005). Treatment-emergent adverse effects with istradefylline were generally mild. Interpretation: Istradefylline was safe, well tolerated, and offered a clinically meaningful reduction in "off" time without increased troublesome dyskinesia. Neurol 2008;63:295-302 Although Parkinson's disease (PD) has several treatment options that initially can provide excellent symptomatic relief, 1 control of its disabilities typically declines over time. Because PD is characterized by loss of dopaminergic neurons projecting from substantia nigra to striatal nuclei, the most rational and effective therapy for restoring dopaminergic neurotransmission has been the dopamine precursor L-dopa. Ann2 Two years after starting L-dopa therapy, however, many patients start to experience fluctuations that interrupt control of parkinsonism, sometimes for up to several hours per day. 3,4 Adjusting the effects of L-dopa (by dosing changes or extenders such as catechol-Omethyltransferase or monoamine oxidase B inhibitors) or adding other dopaminergic drugs can improve "off" (undermedicated) states. Despite these options, inadequate control of motor fluctuations is a major source of disability for chronically treated PD.Beyond restoring dopaminergic input to striatal neurons, other pharmacological interventions can influence From the

This study compares the sensitivity of a Patient Questionnaire versus information gathered by clinicians at a routine clinic visit in recognizing symptoms of wearing-off in early Parkinson's disease (PD). This Patient Questionnaire, containing 32 items representing a wide spectrum of motor and nonmotor wearing-off symptoms, was administered to subjects attending two PD clinics. The Patient Questionnaire results were compared to the information gathered by the clinician from the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV, Question 36 and from a specific Clinical Assessment Question regarding loss of medication efficacy, wearing-off, sleepiness, dyskinesias, psychiatric complications, morning akinesia, other dopaminergic side effects, or none of the above. Examiners were blinded to study hypothesis and survey contents. Three hundred consecutive subjects with PD of <5 years duration were evaluated; the mean subject age was 72 +/- 9.6 years and 60.2% were men. Subjects reporting wearing-off were significantly younger (69.9 vs. 74.7 years) and differed regarding duration of PD symptoms (3.7 vs. 3.1 years). Wearing-off was found in 181 subjects (62.6%) by one or more of the three measures. The most sensitive tool was the Patient Questionnaire, with 165 subjects (57.1%) indicating symptoms of wearing-off. Question 36 of the UPDRS was positive in 127 subjects (43.9%), and the Clinical Assessment Question identified 85 subjects (29.4%) as experiencing wearing-off. All of these results were found to differ significantly. The mean number of wearing-off symptoms reported by the 165 subjects indicating wearing-off on the clinical survey was 6.25, with tremor being the most common motor feature and tiredness the most common nonmotor feature.