Total Unified Parkinson's Disease Rating Scale Score Research Articles

Meta-Analysis of Creatine for Neuroprotection Against Parkinson's Disease.

Creatine is an antioxidant agent that showed neuroprotective effects in animal models of Parkinson's disease (PD). Creatine was selected by the National Institute of Neurological Disorders and Stroke as a possible disease modifying agent for Parkinson's disease. Therefore, many clinical trials evaluated the efficacy of creatine for patients with PD. The aim of this systematic review and meta-analysis is to synthesize evidence from published randomized controlled trials (RCTs) about the efficacy of Creatine for patients with PD. We followed PRISMA statement guidelines during the preparation of this systematic review and meta-analysis. A computer literature search for PubMed, EBSCO, web of science and Ovid Midline was carried out. We included RCTs comparing creatine with placebo in terms of motor functions and quality of life. Outcomes of total Unified Parkinson's Disease Rating Scale (UPDRS), UPDRS I, UPDRS II, and UPDRS III were pooled as mean difference (MD) between two groups from baseline to the endpoint. Statistical heterogeneity was assessed by visual inspection of the forest plot and measured by chi-square and I square tests. Three RCTs (n=1935) were included in this study. The overall effect did not favor either of the two groups in terms of: UPDRS total score (MD 1.07, 95% CI [3.38 to 1.25], UPDRS III (MD 0.62, 95% CI [2.27 to 1.02]), UPDRS II (MD 0.03, 95% CI [0.81 to 0.86], or UPDRS I (MD 0.03, 95% CI [0.33 to 0.28]). Current evidence does not support the use of creatine for neuroprotection against PD. Future well-designed, randomized controlled trials are needed.

A review of disease progression models of Parkinson's disease and applications in clinical trials.

Quantitative disease progression models for neurodegenerative disorders are gaining recognition as important tools for drug development and evaluation. In Parkinson's disease (PD), several models have described longitudinal changes in the Unified Parkinson's Disease Rating Scale (UPDRS), one of the most utilized outcome measures for PD trials assessing disease progression. We conducted a literature review to examine the methods and applications of quantitative disease progression modeling for PD using a combination of key words including "Parkinson disease," "progression," and "model." For this review, we focused on models of PD progression quantifying changes in the total UPDRS scores against time. Four different models reporting equations and parameters have been published using linear and nonlinear functions. The reasons for constructing disease progression models of PD thus far have been to quantify disease trajectories of PD patients in active and inactive treatment arms of clinical trials, to quantify and discern symptomatic and disease-modifying treatment effects, and to demonstrate how model-based methods may be used to design clinical trials. The historical lack of efficiency of PD clinical trials begs for model-based simulations in planning for studies that result in more informative conclusions, particularly around disease modification. © 2016 International Parkinson and Movement Disorder Society.

Metabolic Covariant Network in Relation to Nigrostriatal Degeneration in Carbon Monoxide Intoxication-Related Parkinsonism.

Presence of parkinsonian features after carbon monoxide (CO) intoxication is well known and the severity was found to relate to the pre-synaptic dopaminergic deficits. There is no systemic study to analyse the functional network involved in CO-related Parkinsonism. Forty-five CO-related parkinsonism patients and 25 aged-matched controls completed the 3D T1-weighted imaging and 18F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET). Voxel-based morphometry (VBM) was performed to assess the structural and functional brain differences between the patients and controls. Spatial covariant networks responsible for distinguishing patients and controls were constructed using independent component analysis. For validation, the pre-synaptic dopaminergic functional network was established by regression model using striatal TRODAT-1 SPECT as the independent variable. The clinical significance of both networks was determined by correlation with the Unified Parkinson's Disease Rating Scale (UPDRS). Compared with controls, the spatial covariant signals of FDG-PET were significantly lower in the medial and lateral frontal, caudate nucleus, dorsomedial prefrontal areas, and temporal-parietal regions while the spatial intensities correlated significantly with UPDRS total scores. The functional network that correlated with striatum pre-synaptic dopaminergic uptakes included the midbrain, thalamus, caudate, lateral frontal cortex, ventral striatum, ventral, or dorsal anterior cingulate cortex. Both networks overlapped considerably and the topographies reflected structural damage pattern. Our study provides evidence that glucose metabolism in CO-parkinsonism patients pertains to an organized covariant pattern in the cortical regions that is spatially coherent with the cortical map of pre-synaptic dopamine deficits. As the fronto-temporal, striatum, and temporal-parietal areas were involved, the unique metabolic covariant network suggests a different pathophysiology in CO-related parkinsonism.

Efficacy of rasagiline in early Parkinson's disease: a meta-analysis of data from the TEMPO and ADAGIO studies

Aim of the study: To evaluate the efficacy of rasagiline versus placebo in a pooled population of patients with early Parkinson's disease (PD). Materials and methods: TEMPO and ADAGIO were Phase III studies that evaluated the symptomatic efficacy of rasagiline versus placebo in patients with early PD. This meta-analysis included Unified Parkinson's Disease Rating Scale (UPDRS) observations from weeks 12, 24 and 36 in ADAGIO and from weeks 14 and 26 in TEMPO; TEMPO visits were recoded to weeks 12 and 24, respectively. The present analysis includes all patients who received rasagiline 1 mg/day, 2 mg/day or placebo, and had ≥1 post-baseline observations and a subgroup of patients whose baseline UPDRS Total scores were ≥27 (Upper Quartile population). Change from baseline in UPDRS scores were evaluated using mixed models repeated measures analyses. Results: Of the 1578 patients randomized to the two studies, 1546 patients met criteria for inclusion in the meta-analysis. Effects on UPDRS Total, motor and activities of daily living scores were significantly better for both doses of rasagiline compared with placebo at all time periods. The Upper Quartile population included 402 patients with a UPDRS Total score ≥27 at baseline. These patients generally demonstrated a larger magnitude of treatment effect than was seen in the full population. Conclusions: This meta-analysis confirms the efficacy of rasagiline monotherapy over 36 weeks. Although TEMPO and ADAGIO are considered studies of “very early” PD, both contained a sizeable pool of patients with more severe disease. In addition, the meta-analysis showed a larger magnitude of effect in patients with more severe baseline disease.

Association Between Change in Body Mass Index, Unified Parkinson's Disease Rating Scale Scores, and Survival Among Persons With Parkinson Disease: Secondary Analysis of Longitudinal Data From NINDS Exploratory Trials in Parkinson Disease Long-term Study 1.

Greater body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) is associated with improved survival among persons with Huntington disease or amyotrophic lateral sclerosis. Weight loss is common among persons with Parkinson disease (PD) and is associated with worse quality of life. To explore the association between change in BMI, Unified Parkinson's Disease Rating Scale (UPDRS) motor and total scores, and survival among persons with PD and to test whether there is a positive association between BMI at randomization and survival. Secondary analysis (from May 27, 2014, to October 13, 2015) of longitudinal data (3-6 years) from 1673 participants who started the National Institute of Neurological Disorders and Stroke Exploratory Trials in PD Long-term Study-1 (NET-PD LS-1). This was a double-blind randomized placebo-controlled clinical trial of creatine monohydrate (10 g/d) that was performed at 45 sites throughout the United States and Canada. Participants with early (within 5 years of diagnosis) and treated (receiving dopaminergic therapy) PD were enrolled from March 2007 to May 2010 and followed up until September 2013. Change across time in motor UPDRS score, change across time in total UPDRS score, and time to death. Generalized linear mixed models were used to estimate the effect of BMI on the change in motor and total UPDRS scores after controlling for covariates. Survival was analyzed using Cox proportional hazards models of time to death. A participant's BMI was measured at randomization, and BMI trajectory groups were classified according to whether participants experienced weight loss ("decreasing BMI"), weight stability ("stable BMI"), or weight gain ("increasing BMI") during the study. Of the 1673 participants (mean [SD] age, 61.7 [9.6] years; 1074 [64.2%] were male), 158 (9.4%) experienced weight loss (decreasing BMI), whereas 233 (13.9%) experienced weight gain (increasing BMI). After adjusting for covariates, we found that the weight-loss group's mean (SE) motor UPDRS score increased by 1.48 (0.28) (P < .001) more points per visit than the weight-stable group's mean (SE) motor UPDRS score. The weight-gain group's mean (SE) motor UPDRS score decreased by -0.51 (0.24) (P = .03) points per visit, relative to the weight-stable group. While there was an unadjusted difference in survival between the 3 BMI trajectory groups (log-rank P < .001), this was not significant after adjusting for covariates. Change in BMI was inversely associated with change in motor and total UPDRS scores in the NET-PD LS-1. Change in BMI was not associated with survival; however, these results were limited by the low number of deaths in the NET-PD LS-1. clinicaltrials.gov Identifier: NCT00449865.

Coenzyme Q10 for Patients with Parkinson's Disease: A Systematic Review and Meta-Analysis.

Coenzyme Q10 (CoQ10) is an antioxidant that enhances the activity of complex I and II in the Electron Transport Chain. Many preclinical and clinical studies evaluated CoQ10 for neuroprotection against Parkinson's disease (PD). The aim of this study is to synthesize evidence from published randomized controlled trials (RCTs) about the benefit of CoQ10 supplementation for patients with Parkinson's disease. We followed the PRISMA statement guidelines during the preparation of this systematic review and metaanalysis. A computer literature search for (PubMed, EBSCO, Web of science and Ovid Midline) was carried out. We included RCTs comparing CoQ10 with placebo in terms of motor functions and quality of life. Outcomes of total Unified Parkinson's Disease Rating Scale (UPDRS), UPDRS I, UPDRS II, UPDRS III and Schwab and England scores were pooled as standardized mean difference (SMD) between two groups from baseline to the endpoint. Five RCTs (981 patients) were included in this study. The overall effect did not favor either of the two groups in terms of: total UPDRS score (SMD -0.05, 95%CI [-0.10, 0.15]), UPDRS I (SMD -0.03, 95% CI [-0.23, 0.17]), UPDRS II (SMD -0.10, 95%CI [-0.35, 0.15]), UPDRS III (SMD -0.05, 95%CI [-0.07, 0.17]) or Schwab and England score (SMD 0.08, 95%CI [-0.13, 0.29]). CoQ10 supplementation does not slow functional decline nor provide any symptomatic benefit for patients with Parkinson's disease.

Cognitive and Motor Aspects of Parkinson's Disease Associated with Dysphagia.

Dysphagia is a common symptom and an important prognostic factor in Parkinson's disease (PD). Although cognitive and motor dysfunctions may contribute to dysphagia in patients with PD, any specific association between such problems and swallowing functions is unclear. Here, we examined the potential relationship between cognitive/motor components and swallowing functions in PD. We evaluated the contributions of cognition and motor function to the components of swallowing via video fluoroscopic swallowing (VFS) experiments. We prospectively enrolled 56 patients without dementia having PD. Parkinson's disease severity was assessed by the Unified Parkinson's Disease Rating Scale (UPDRS). All participants received neuropsychological tests covering general mental status, visuospatial function, attention, language, learning and memory, and frontal executive function. The well-validated "modified barium swallow impairment profile" scoring system was applied during VFS studies to quantify swallowing impairments. Finally, correlations between neuropsychological or motor functions and impairment in swallowing components were calculated. The most significant correlations were found between the frontal/executive or learning/memory domains and the oral phase of swallowing, though a minor component of the pharyngeal phase correlated with frontal function as well. Bradykinesia and the UPDRS total score were associated with both the pharyngeal and oral phases. Our findings suggest that cognitive dysfunctions are associated with the oral phase of swallowing in patients with early stage PD while the severity of motor symptoms may be associated with overall swallowing function.

Randomized, double-blind, placebo-controlled pilot trial of reduced coenzyme Q10 for Parkinson's disease.

Mitochondrial complex I deficiencies have been found in post-mortem brains of patients with Parkinson's disease (PD). Coenzyme Q10 (CoQ10) is the electron acceptor found in complexes I and II, and is a potent antioxidant. A recent trial of the oxidized form of CoQ10 for PD failed to show benefits; however, the reduced form of CoQ10 (ubiquinol-10) has shown better neuroprotective effects in animal models. Randomized, double-blind, placebo-controlled, parallel-group pilot trials were conducted to assess the efficacy of ubiquinol-10 in Japanese patients with PD. Participants were divided into two groups: PD experiencing wearing off (Group A), and early PD, without levodopa (with or without a dopamine agonist) (Group B). Participants took 300 mg of ubiquinol-10 or placebo per day for 48 weeks (Group A) or 96 weeks (Group B). In Group A, total Unified Parkinson's Disease Rating Scale (UPDRS) scores decreased in the ubiquinol-10 group (n = 14; mean ± SD [-4.2 ± 8.2]), indicating improvement in symptoms. There was a statistically significant difference (p < 0.05) compared with the placebo group (n = 12; 2.9 ± 8.9). In Group B, UPDRS increased in the ubiquinol-10 group (n = 14; 3.9 ± 8.0), as well as in the placebo group (n = 8; 5.1 ± 10.3). This is the first report showing that ubiquinol-10 may significantly improve PD with wearing off, as judged by total UPDRS scores, and that ubiquinol-10 is safe and well tolerated.

Continuous dopaminergic stimulation (CDS)-based treatment in Parkinson's disease patients with motor complications: a systematic review and meta-analysis.

A systematic review of the literature was conducted to identify randomized trials involving continuous dopaminergic stimulation (CDS) in PD patients with motor complications. Difference between n groups was assessed by partitioning heterogeneity and using the χ2 distribution with n-1 degrees of freedom, where n equals the number of groups. We looked for publication bias using funnel plotting, Egger's test and Begg's test. Twenty Randomized Controlled Trials (RCTs) were included. The results showed that CDS could evidently improve the Unified Parkinson's Disease Rating Scale (UPDRS) Part II (p < 0.0001), part III (P < 0.00001) and UPDRS total score (p < 0.00001). There was also a statistical discrepancy in off time reduction (p < 0.00001) and prolongation of on time (p < 0.00001) by the CDS therapy compared with control groups. Meanwhile, the results of this study showed obvious side effects in the CDS therapy compared with the placebo, especially at the expense of increased dyskinesia (23.4% vs 11.7%). The present study showed that CDS was beneficial in the treatment of PD patients with motor complications. But the incidence of the side events is more common than placebo.

Randomized, controlled trial of rasagiline as an add-on to dopamine agonists in Parkinson's disease.

Dopamine agonists (DA) are often used as first-line monotherapy for the symptomatic control of Parkinson's disease (PD). However, DA monotherapy typically becomes inadequate within a few years, at which time the DA dosage must be increased or other antiparkinsonian medications added. Adding a monoamine oxidase-B (MAO-B) inhibitor to DA monotherapy might improve symptomatic control while maintaining good safety and tolerability. We conducted an 18-week, randomized, double-blind, placebo-controlled trial of rasagiline 1 mg/d as an add-on to DA therapy (ropinirole ≥ 6 mg/d or pramipexole ≥ 1.0 mg/d) in early PD patients whose conditions were not adequately controlled on their current treatment regimen. The primary efficacy variable was the change in total Unified Parkinson Disease Rating Scale (UPDRS) score (sum of parts I, II, and III) from baseline to week 18, comparing rasagiline and placebo groups. The modified intent-to-treat (ITT) population included 321 subjects whose mean ± SD age was 62.6 ± 9.7, and duration of PD was 2.1 ± 2.1 years. Results demonstrated a significantly greater improvement in total UPDRS scores from baseline to week 18 in the rasagiline group compared with the placebo group (least squares [LS] mean difference ± SE, -2.4 ± 0.95; 95% confidence interval [CI], -4.3, -0.5; P = 0.012). Mean improvement (LS mean ± SE) was -3.6 ± 0.68 in the rasagiline group and -1.2 ± 0.68 in the placebo group. Rasagiline was well tolerated, and the most common adverse events (AEs; rasagiline vs. placebo) were dizziness (7.4% vs. 6.1%), somnolence (6.8% vs. 6.7%), and headache (6.2% vs. 4.3%). Rasagiline 1 mg/d provided statistically significant improvement when added to dopamine agonist therapy and was well tolerated.

A Randomized Clinical Trial of High-Dosage Coenzyme Q10 in Early Parkinson Disease

Coenzyme Q10 (CoQ10), an antioxidant that supports mitochondrial function, has been shown in preclinical Parkinson disease (PD) models to reduce the loss of dopamine neurons, and was safe and well tolerated in early-phase human studies. A previous phase II study suggested possible clinical benefit. To examine whether CoQ10 could slow disease progression in early PD. A phase III randomized, placebo-controlled, double-blind clinical trial at 67 North American sites consisting of participants 30 years of age or older who received a diagnosis of PD within 5 years and who had the following inclusion criteria: the presence of a rest tremor, bradykinesia, and rigidity; a modified Hoehn and Yahr stage of 2.5 or less; and no anticipated need for dopaminergic therapy within 3 months. Exclusion criteria included the use of any PD medication within 60 days, the use of any symptomatic PD medication for more than 90 days, atypical or drug-induced parkinsonism, a Unified Parkinson's Disease Rating Scale (UPDRS) rest tremor score of 3 or greater for any limb, a Mini-Mental State Examination score of 25 or less, a history of stroke, the use of certain supplements, and substantial recent exposure to CoQ10. Of 696 participants screened, 78 were found to be ineligible, and 18 declined participation. The remaining 600 participants were randomly assigned to receive placebo, 1200 mg/d of CoQ10, or 2400 mg/d of CoQ10; all participants received 1200 IU/d of vitamin E. Participants were observed for 16 months or until a disability requiring dopaminergic treatment. The prospectively defined primary outcome measure was the change in total UPDRS score (Parts I-III) from baseline to final visit. The study was powered to detect a 3-point difference between an active treatment and placebo. The baseline characteristics of the participants were well balanced, the mean age was 62.5 years, 66% of participants were male, and the mean baseline total UPDRS score was 22.7. A total of 267 participants required treatment (94 received placebo, 87 received 1200 mg/d of CoQ10, and 86 received 2400 mg/d of CoQ10), and 65 participants (29 who received placebo, 19 who received 1200 mg/d of CoQ10, and 17 who received 2400 mg/d of CoQ10) withdrew prematurely. Treatments were well tolerated with no safety concerns. The study was terminated after a prespecified futility criterion was reached. At study termination, both active treatment groups showed slight adverse trends relative to placebo. Adjusted mean changes (worsening) in total UPDRS scores from baseline to final visit were 6.9 points (placebo), 7.5 points (1200 mg/d of CoQ10; P = .49 relative to placebo), and 8.0 points (2400 mg/d of CoQ10; P = .21 relative to placebo). Coenzyme Q10 was safe and well tolerated in this population, but showed no evidence of clinical benefit. clinicaltrials.gov Identifier: NCT00740714.

Actigraphy monitoring of symptoms in patients with Parkinson's disease

Although the Unified Parkinson's Disease Rating Scale (UPDRS) is the “gold-standard” tool in assessing the severity of symptoms in patients with Parkinson's disease (PD), not all activity-related disease symptoms can be accurately captured by the well-established clinical rating scale. Using an alternative approach, this study examined the level of physical activity measured by actigraphy over time and whether change in physical activity was associated with disease severity assessed by UPDRS.We used a longitudinal design in which physical activity and disease severity were assessed repeatedly during a 4-month interval, over a 3-year observational period, in a sample of 61 patients with idiopathic PD and a control group of 32 neurologically intact individuals. Physical activity data during awake-time were analyzed using the power-law exponent (PLE) method. Correlational relationships between changes in maxima values of PLE and scores of total UPDRS, UPDRS—part II (Activities of Daily Living), and UPDRS—part III (Motor Examination) in patients with PD were examined. Results show an increase in maxima values of PLE and the UPDRS total score in PD patients and that there is a positive association between changes in maxima values and total UPDRS score (r=0.746, p=0.032), UPDRS—part II score (r=0.687, p=0.027), and UPDRS—part III score (r=0.893, p=0.018). There was no significant change in the level of physical activity over time for the controls.Findings from this study indicate that change in physical activity, as captured by actigraphy, is associated with increased severity in patients' clinical symptoms of PD over time. Thus, these data suggest that, when used in conjunction with the conventional UPDRS measure, an actigraphic measure of physical activity may provide clinicians an adjunct measurement approach to monitor patients' activity-based disease progression or responses to treatment in outpatient clinic settings.

Relationship Between Cognitive Dysfunction and Behavioural Symptoms in Nigerian Patients with Parkinson's Disease No dementia

There is presently no information on the behavioural symptoms that are related to cognitive dysfunction in African patients with Parkinson's disease. This study highlights the behavioral symptoms that are related to global cognitive dysfunction without dementia, as well as the caregivers' distress they create in a population of Nigerians with idiopathic Parkinson's disease. Fifty patients with idiopathic Parkinson's disease, confirmed using the United Kingdom Parkinson's Disease Society (UKPDS) Brain Bank Clinical Diagnostic Criteria, were cross-sectionally assessed for cognitive functions using the modified Mini-mental State Examination (MMSE), motor symptoms using the Unified Parkinson's disease Rating Scale (UPDRS), as well as neuropsychiatric symptoms and caregivers' distress using the Neuropsychiatric Inventory (NPI). Additional information obtained from all the participants and their caregivers included demographic data, personal history, psychiatric history, medical history and family history. The behavioural, caregivers' distress and motor correlates of cognitive dysfunction were explored. In all, 24.0% of the patients had cognitive dysfunction according to the local norm of the MMSE. Hallucinations (Chi2 = 5.556, p = 0.018) and agitation (Chi2 = 5.556, p = 0.018) were related to cognitive dysfunctions. There was more behaviour related caregivers' distress in those with cognitive dysfunction than those without (Chi2 = 2.208, p = 0.032). The MMSE scores correlated inversely with the score for rigidity (r = -0.506, p = 0.0002), bradykinesia (r = -0.592, p < 0.0001), and the UPDRS total score (r = -0.503, p = 0.0002). The psychotic symptoms of hallucinations and agitations differentiated Parkinson's disease patients with cognitive dysfunction from those with normal cognition. Generally, the presence of behavioural symptom led to more distress in the caregivers of patients with cognitive dysfunction.

Quantitative Evaluation of Movement Disorders by Specified Analysis According to Actigraphy Records

Aim: To evaluate whether the specified analytical objective scale represents disease severity for neurological movement disorders according to the physical activity of the patients. Methods: Eighty-one patients with Parkinsonʹs disease (PD) and sixty-one patients with acute cerebral infarction (ACI) combined with upper limb motor function disorder at the Shuguang hospital, affiliated with the Shanghai TCM university. PD patients and ACI patients were treated according to the international medication guiding principle for PD or ACI respectively. We analysed the power-law exponent (PLE) and the detrended fluctuation analysis (DFA) of the actigraphy records, which were taken on 2 occasions (before drug administration for two groups, 24-38 days for PD patients and 28 days for ACI patients). Efficacy was evaluated by the Unified Parkinson Disease Rating Scale (UPDRS) for PD and by Fugl-Meyer Assessment (FMA) and the Functional Independence Measure (FIM) for ACI patients. We also evaluated the correlation between any changed rates of UPDRS scores and PLE for PD patients, and FMA and FIM scores and DFA for ACI patients. Results: The UPDRS scores and PLE values for PD, and the FMA and FIM scores with the DFA score for ACI were improved after the drug administration; they yielded a linear correlation coefficient of 0.699 and 0.823 between the improvement rates of the total UPDRS scores and the PLE values, and between the UPDRS Part III score and the PLE values, while it yielded a linear correlation coefficient of 0.638 and 0.712 between the improvement rates of the FMA scores and the DFA, and the FIM scores and the DFA respectively. There was no correlation between the UPDRS scores and the DFA values for the PD patients or between the FIM score or the FMA score and the PLE values for ACI patients. Conclusion: Actigraphy records and the analysis of its PLE or DFA might provide useful objective and specific information for controlling PD or ACI patients and for monitoring drug administration respectively.

Treating Parkinson's disease with high and low frequency repetitive transcranial magnetic stimulation: a clinical study

Objective To investigate the therapeutic effects of repeated transcranial magnetic stimulation (rTMS) at high and low frequency for the rigidity and tremors of Parkinson's disease (PD).Methods Sixty-nine patients with PD received rTMS at 5 Hz or 0.5 Hz.The efficacy was assessed using the unified Parkinson's disease rating scale (UPDRS),motor function tests and motor evoked potentials (MEPs).Results Thirty-two patients with rigidity from PD received 5 Hz rTMS therapy,and their UPDRS total scores decreased significantly.Their motor function test results improved significantly and their MEP relaxed motor thresholds were significantly elevated.Thirtyseven patients with tremors from PD received 0.5 Hz rTMS therapy,and their UPDRS total scores were significantly decreased.Their motor function test results improved significantly and their MEP relaxed motor thresholds were significantly elevated.Conclusion High frequency rTMS may improve the symptoms of patients with PD rigidity and low frequency rTMS may improve the symptoms of patients with PD tremors. Key words: Parkinson's disease; Transcranial magnetic stimulation; Motor evoked potentials

The UPDRS-8: A Brief Clinical Assessment Scale for Parkinson's Disease

ABSTRACTWe evaluated a brief, 8-item version of the Unified Parkinson's Disease Rating Scale (UPDRS) using two existing patient databases. One database included 1,445 PD patients. Spearman correlation between UPDRS-8 motor scores and full UPDRS motor scores was .765 (p < .001). Correlation between total UPDRS-8 scores and full UPDRS total scores (parts I–III) was .798 (p < .001). Correlation between total UPDRS-8 scores and total 39-item PD questionnaire (PDQ-39) scores was .629 (p < .001). In 177 patients undergoing deep brain stimulation (DBS), UPDRS-8 motor scores were similarly significantly sensitive to change as full UPDRS motor scores in assessing change from the medication OFF state to the medication ON state at baseline and from the medication OFF state at baseline to the medication OFF/stimulation ON state 1 year post-DBS. The UPDRS-8 focuses on items that are most relevant for clinical decision making. In this study, the UPDRS-8 exhibited good correlation with the full UPDRS and the PDQ-39. We therefore believe that it can provide a useful, rapid assessment of PD patients in clinical practice. Whether it might be useful in clinical trials depends on demonstrating that it is also sensitive to relatively small changes in clinical status.

The Relationship Between the Grooved Pegboard Test and Clinical Motor Symptom Evaluation Across the Spectrum of Parkinson's Disease Severity

The Unified Parkinson's Disease Rating Scale (UPDRS) is the gold standard for assessing Parkinsonian symptoms, yet objective outcome measures are needed to complement the UPDRS in research and clinical practice. This study aimed to investigate the relationship between performance on the Grooved Pegboard Test (GP) and clinical assessment of Parkinson's motor symptoms with the UPDRS. A large sample of individuals with Parkinson's disease (n = 191) were assessed with the GP and UPDRS motor section. The GP was separated into a place (more representative of visuospatial accuracy) and remove phase (general representation of motor speed and bradykinesia). Both tests were completed at peak anti-parkinsonian medication levels, and UPDRS subscores were calculated to represent upper-limb control, rigidity, bradykinesia, and tremor. A subsequent correlation analysis was completed. The strongest relationships were between the GP place phase (both limbs) and total UPDRS motor score (affected: r = 0.604, less-affected: r = 0.587), upper-limb control (affected: r = 0.367, less-affected: r = 0.426), rigidity (affected: r = 0.479, less-affected: r = 0.457) and body bradykinesia (affected: r = 0.375, less-affected: r = 0.438). The GP remove phase had weak positive relationships with total UPDRS scores (affected: r = 0.31, less-affected r = 0.31) and body bradykinesia (r = 0.31). Clinical assessment of upper-limb control, rigidity and bradykinesia are well represented by the GP place phase. Interestingly, it appeared that GP performance of the more affected limb may be more representative of motor severity in the early stages of disease, while more research is needed to understand the utility of the GP in the advanced stages of disease.

Deep brain stimulation of the subthalamic nucleus for advanced Parkinson disease using general anesthesia: long-term results

The authors analyze long-term outcome in a substantial number of patients who underwent subthalamic nucleus (STN) deep brain stimulation (DBS) surgery under general anesthesia. Eighty-two patients underwent bilateral placement of DBS electrodes under general anesthesia for advanced Parkinson disease; the STN was the target in all cases. All patients underwent intraoperative microelectrode recording of the STN. No intraoperative macrostimulation was performed. Unified Parkinson's Disease Rating Scale (UPDRS) data were recorded in 28 patients. Assessment of outcome was performed using the UPDRS (in 28 cases), the electrophysiological recordings (in all 82 cases), medication reduction (in 78 cases), and complications (in 82 cases). There was improvement in UPDRS scores across all measures following surgery. The total UPDRS score, off medication, improved from 68.78 (geometrical mean, 95% CI 61.76-76.60) preoperatively to 45.89 (geometrical mean, 95% CI 34.86-60.41) at 1 year postoperatively (p = 0.003, data available in 26 patients). Improvements were obtained in UPDRS Part II (Activities of Daily Living) off medication (p = 0.001) and also UPDRS Part III (Motor Examination) off medication (p < 0.001). Results for the on-medication and on-stimulation states also showed a statistically significant improvement for UPDRS Part III (p = 0.047). Good microelectrode recording of the STN was obtained under general anesthesia; the median first-track length was 4.0 mm, and the median number of tracks passed per patient was 3.0. The median reduction in levodopa medication was 58.1% (interquartile range 42.9%-73.3%). One patient had an intracerebral hemorrhage in the track of 1 electrode but did not require surgical evacuation. One patient had generalized convulsive seizures 24 hours postoperatively and was intubated for seizure control. Unified Parkinson's Disease Rating Scale scores were obtained in 26 patients at 1 year, 28 patients at 3 years, 17 at 5 years, and 7 at 7 years postoperatively. Up to 7 years postoperatively, there was sustained improvement in the total UPDRS score. The results in these patients showed minimal deterioration in the motor section of the UPDRS over time, up to 7 years following the operation. The authors found no evidence that the UPDRS Part II scores changed significantly over the period of 1-7 years after surgery (p = 0.671, comparison of mean scores at 1 and 7 years using generalized estimating equations). Long-term outcomes confirm that it is both safe and effective to perform STN DBS under general anesthesia. As part of patient choice, this option should be offered to all DBS candidates with advanced Parkinson disease to enable more of these patients to undergo this beneficial surgery.

Determination of minimal clinically important change in early and advanced Parkinson's disease

Two common primary efficacy outcome measures in Parkinson's disease (PD) are change in Unified Parkinson's Disease Rating Scale (UPDRS) scores in early PD and change in "off" time in patients with motor fluctuations. Defining the minimal clinically important change (MCIC) in these outcome measures is important to interpret the clinical relevance of changes observed in clinical trials and other situations. We analyzed data from 2 multicenter, placebo-controlled, randomized clinical trials of rasagiline; TEMPO studied 404 early PD subjects, and PRESTO studied 472 levodopa-treated subjects with motor fluctuations. An anchor-based approach using clinical global impression of improvement (CGI-I) was used to determine MCIC for UPDRS scores and daily "off" time. MCIC was defined as mean change in actively treated subjects rated minimally improved on CGI-I. Receiver operating characteristic (ROC) curves defined optimal cutoffs discriminating between changed and unchanged subjects. MCIC for improvement in total UPDRS score (parts I-III) in early PD was determined to be -3.5 points based on mean scores and -3.0 points based on ROC curves. In addition, we found an MCIC for reduction in "off" time of 1.0 hours as defined by mean reduction in "off" time in active treated subjects self-rated as minimally improved on CGI-I minus mean reduction in "off" time in placebo-treated subjects self-rated as unchanged (1.9-0.9 hours). We hypothesize that many methodological factors can influence determination of the MCIC, and a range of values is likely to emerge from multiple studies.

Use of the Unified Parkinson’s Disease Rating Scale Activities of Daily Living Subscale to Assess Response to Rasagiline in Early Parkinson’s Disease

Various assessment scales are used to measure the severity and rate of progression of Parkinson’s disease (PD)—for example, the Unified Parkinson's Disease Rating Scale (UPDRS) and its Activities of Daily Living (ADL) subscale. The relative merits of these scales for accurately determining the degree of disease progression have recently come under scrutiny. Analyses of data from the recent Attenuation of disease progression with Azilect given once daily (ADAGIO) trial demonstrated that patients receiving early-start rasagiline (Azilect®, Teva Neuroscience, North Wales, PA) 1 mg/day experienced slower disease progression, as assessed by their mean total UPDRS score, than patients receiving placebo followed by delayed-start rasagiline treatment. Subsequent secondary analyses showed that 1 and 2 mg/day doses of early-start rasagiline delayed the need for antiparkinsonian drugs and improved other parameters, including ADL scores and fatigue, when compared with placebo followed by delayed-start rasagiline. Furthermore, the analyses highlighted that, over time, the motor and mentation sections of the UPDRS-ADL subscale increasingly reflect the response to treatment of the early- and delayed-start rasagiline 1 mg/day patient groups. The results from the ADAGIO trial suggest that rasagiline has potential disease-modifying effects, but more clinical data are required to confirm their effect on PD progression.