Comparison of a timed motor test battery to the Unified Parkinson's Disease Rating Scale‐III in Parkinson's disease

The most widely used scale currently available for the clinical evaluation of motor dysfunction in Parkinson's disease (PD)—the Unified Parkinson's Disease Rating Scale‐III (UPDRS‐III) —is time‐consuming, subjective, and has suboptimal sensitivity. A brief timed motor test (TMT) battery could possibly overcome these drawbacks. Two hundred eighty‐eight PD patients (disease duration 3.1 years; preceding dopaminergic treatment initiation) were assessed with the UPDRS‐III and nine TMTs based on aspects of (a) walking, (b) writing, (c) single and double‐handed pegboard performance, (d) finger tapping, and (e) rapid alternating forearm movements. We investigated validity, reliability, responsiveness, and feasibility. Completing the TMT battery took less than 5 minutes. The TMT correlated well with UPDRS‐III and disease duration. Two factors explained 61% of the TMT variance, the first represented mainly upper extremity function, the second mainly axial/lower extremity function. Cronbach's α was equal for the TMT and the UPDRS‐III (0.8). Test–retest reliability of the TMT sumscore was 0.93 to 0.89 for measurements separated by 3 up to 24 months, whereas UPDRS‐III correlations were 0.88 to 0.84. At group level, a trial using “change from baseline” as endpoint requires only 75% of the patients needed with the UPDRS‐III when applying the TMT battery, and 57% using the pegboard dexterity test. At patient level, TMT and UPDRS‐III were equally responsive. The TMT battery described here is valid, reliable, and feasible. Compared to the UPDRS‐III, it is more objective and more sensitive to change. Therefore, it could be a useful tool for both practical and scientific purposes. © 2008 Movement Disorder Society     

Kinematic analysis of dopaminergic effects on skilled handwriting movements in Parkinson’s disease

Summary. Patients with Parkinson’s disease (PD) exhibit impairments in the execution of highly practiced and skilled motor actions such as handwriting. The analysis of kinematic aspects of handwriting movements has demonstrated that size, speed, acceleration and stroke duration are affected in PD. Although beneficial effects of dopaminergic therapy in regard to execution of movements have been reported, the effects of pharmacological therapy on these measures have not been examined in detail. The present study has compared kinematic aspects of handwriting movements of 27 healthy subjects and 27 patients with PD both on their usual dopaminergic treatment and following withdrawal of dopaminergic medication. Healthy subjects were matched with PD patients according to age, sex, handedness and education level. A digitising tablet was used for the assessment of handwriting movements. Subjects were asked to perform a simple writing task. Movement time, distance, velocity, acceleration and measures of fluency of handwriting movements were measured. Compared with healthy subjects, the kinematics of handwriting movements in PD patients were markedly disturbed following withdrawal of dopaminergic medication. Although dopaminergic treatment in PD patients resulted in marked improvements in the kinematics of handwriting movements, PD patients did not reach an undisturbed level of performance. The results suggest that dopamine medication results in partial restoration of automatic movement execution.     

Orodispersible sublingual piribedil to abort OFF episodes: A single dose placebo‐controlled,randomized, double‐blind,cross‐over study

S90049, a novel sublingual formulation of the non‐ergoline D₂‐D₃ agonist piribedil, has a pharmacokinetic profile promising to provide rapid relief on motor signs in Parkinson's disease (PD). We assessed the efficacy and safety of S90049 in aborting OFF episodes responding to subcutaneous apomorphine in PD patients with motor fluctuations. This was a single‐dose double‐blind double‐placebo 3 × 3 cross‐over study. Optimal tested doses were determined during a previous open‐label titration phase (S90049 median dose: 60 mg, apomorphine: 5 mg). Primary endpoint was the maximal change versus baseline in UPDRS motor score (ΔUPDRS III) assessed after drug administration following an overnight withdrawal of antiparkinsonian medications. Thirty patients (age: 60 ± 8 years, PD duration: 12 ± 6 years, UPDRS III OFF: 37 ± 15) participated. S90049 wassuperior to placebo on ΔUPDRS III (?13 ± 12 versus ?7 ± 9 respectively; estimated difference ?5.2, 95% Confidence Interval (CI)[?10.4;0.05], P = 0.05). This was also true for secondary outcomes: number of patients switching from OFF to ON (17 on S90049 vs. 8 on placebo, P = 0.03), time to turn ON (P = 0.013) and duration of the ON phase (P = 0.03). In the 17 patients who switched ON on S90049, ΔUPDRS III was similar on S90049 (?21.2 ± 10.1) and apomorphine (?23.6 ± 14.1) (estimated difference: 4.0 95% CI [?2.9;10.9]). S90049 was well tolerated: no serious or unexpected adverse event occurred. A single dose of up to 60 mg of S90049 given sublingually was superior to placebo in improving UPDRS III and aborting a practical OFF in patients with advanced PD. Testing greater doses might improve response rate. © 2009 Movement Disorder Society     

The changes of exercise pattern and clinical symptoms in patients with Parkinson's disease in the era of COVID-19 pandemic

IntroductionThe coronavirus disease 2019 (COVID-19) pandemic has disrupted everyday life of Parkinson's disease (PD) patients, but its clinical impact has not been illustrated. In this study, we investigated the change in physical activity and subsequently clinical symptoms of PD during the COVID-19 pandemic.MethodsWe enrolled PD patients who were able to ambulate independently and had visited our clinic at Samsung Medical Centre from December 2019 to January 2020 (baseline) and in May 2020 (follow-up during the COVID-19 crisis), and divided them into either ‘the sustained exercise group’ or ‘the reduced exercise group’. Then, we assessed the change in the exercise and clinical features between these two groups over the study period.ResultsA total of 100 subjects were recruited. During the COVID-19 pandemic, the amount, duration and frequency of exercise were reduced. There was decrease in number of patients who do indoor-solo exercise and increase in that of patients who do not exercise. One third reported subjective worsening of both motor and non-motor features, although Unified PD Rating Scale (UPDRS) part 3 score was similar. Additionally, the reduced exercise group reported more motor and non-motor aggravation than the sustained exercise group, despite lack of significant difference in the UPDRS part 3 score.ConclusionThe COVID-19 pandemic had a clear impact on exercise and subjective symptoms in PD patients, with reduced exercise being related to a subjective increase in both motor and non-motor symptoms of PD. Maintaining exercise should therefore be emphasized even in situations like the COVID-19 pandemic.     

Comparison of the effects of a self-supervised home exercise program with a physiotherapist-supervised exercise program on the motor symptoms of Parkinson's disease.

The effects of a self-supervised home exercise program and a physiotherapist-supervised exercise program on motor symptoms in Parkinson's disease (PD) patients were compared in a prospective single-blinded clinical trial. Nineteen subjects (6 women, 13 men; mean age, 65 +/- 8 years) with Hoehn and Yahr Stages 2 to 3 were recruited. Subjects were self-selected into an 8-week exercise program that was self-supervised (HOME group) or physiotherapist-supervised (PT group). The primary outcome measurement was the Unified Parkinson's Disease Rating Scale (UPDRS) Motor subsection score (UPDRSm). The secondary outcome measurements were the Berg Balance Scale, Timed Up and Go Test, UPDRS Total score, and the Activities-specific Balance Confidence Scale. All outcomes were assessed at baseline and at 8 and 16 weeks after the start of the study. The investigators were blinded to the subject treatment group. Bonferroni-corrected paired Student's t test was used to evaluate the change in the UPDRSm from baseline to 8 weeks. Ninety-five percent confidence intervals (CI) were calculated for the change in the secondary outcome measurements from baseline to 8 weeks. There was statistically significant and equal decrease in the UPDRSm from baseline to 8 weeks in both treatment groups. There was no difference in the 95% CI in the change of the secondary outcome measurements. A self-supervised exercise program was found to have similar effectiveness as a physiotherapist-supervised exercise program in improving motor symptoms in PD patients. This finding is important in the counseling of PD patients regarding adjunctive treatment of motor symptoms of PD with exercise.     

The effect of computer-assisted therapeutic practice for children with handwriting deficit: A comparison with the effect of the traditional sensorimotor approach

The objective of this study was to compare the effect of computer-assisted practice with the sensorimotor approach on the remediation of handwriting problems in children with dysgraphia. In a randomized controlled trial, experiments were conducted to verify the intervention effect. Forty two children with handwriting deficit were assigned to computer-assisted instruction, sensorimotor training, or a control group. Handwriting performance was measured using the elementary reading/writing test and computerized handwriting evaluation before and after 6 weeks of intervention. Repeated-measures ANOVA of changed scores were conducted to show whether statistically significant differences across the three groups were present. Significant differences in the elementary reading/writing test were found among the three groups. The computer group showed more significant improvements than the other two groups did. In the kinematic and kinetic analyses, the computer group showed promising results in the remediation of handwriting speed and fluency. This study provided clinical evidence for applying a computer-assisted handwriting program for children with dysgraphia. Clinicians and school teachers are provided with a systematic intervention for the improvement of handwriting difficulties.     

P型和C型多系统萎缩的急性多巴反应性研究

目的研究P型和C型多系统萎缩（MSA）对左旋多巴的急性反应性。方法对P型MSA患者18例、C型MSA患者13例和帕金森病（PD）患者23例行急性阶梯式左旋多巴试验，药物剂量依次为左旋多巴／苄丝肼50mg／12．5mg、100mg／25mg、150mg／37．5mg、200mg／50mg和300mg／75mg。以UPDRS运动分量表作为评价标准，计算UPDRS运动评分平均最大改善率并比较各组患者的多巴反应性。结果左旋多巴／苄丝肼剂量为。100mg／25mg、150．mg／37．5mg、200mg／50mg和300mg／75mg时，MSA-P型组和MSA—C型组韵UPDRS运动评分平均最大改善率均显著低于PD组，MSA-P型组高于MSA-C型组。MSA-P型组患者随服用左旋多巴／苄丝肼剂量增加UPDRS评分平均最大改善率呈逐渐增高趋势，而MSA-C型不同剂量间UPDRS评分平均最大改善率差异无统计学意义。结论MSA-P型组具有剂量依赖的急性多巴反应性，而MSA-C型组基本无急性多巴反应性。     

Changes in kinetics and kinematics of handwriting during a prolonged writing task in children with and without dysgraphia

Handwriting difficulties or dysgraphia have a profound impact on children's psychosocial development, and yet, 10-30% of school-aged children are reported to experience difficulties mastering this skill. Several studies have examined the nature and biomechanical underpinnings of handwriting difficulties in children with and without dysgraphia. While the majority of these studies have considered short handwriting activities involving a sentence or a paragraph, handwriting quality and speed are reported to vary with the length of the writing task. Further, it is suggested that the biomechanics of handwriting also evolve over extended writing periods, and that these changes may be distinct between children with and without dysgraphia. The nature and specificity of these biomechanical alterations remain unknown. To address this knowledge gap, we examined changes in writing speed, grip forces on the pen barrel, and normal forces on the writing surface, over the course of a 10-min writing task, in a large cohort of 4th grade children with and without dysgraphia. Horizontal stroke speed, grip force and normal force increased over time while vertical stroke speed decreased in all children. These biomechanical changes may be attributable to physical and psychological fatigue and the corresponding compensatory processes invoked by the motor system.     

水中运动训练对帕金森病患者运动功能、平衡功能和行走能力的康复作用

目的探讨水中运动训练对帕金森病患者运动功能、平衡功能和行走能力的康复作用。方法共40例原发性帕金森病患者随机接受常规陆上康复训练(陆上组,20例)和水中运动训练(水中组,20例),分别于训练前和训练8周时采用统一帕金森病评价量表第三部分(UPDRSⅢ)评价运动功能、Berg平衡量表(BBS)和起立-行计时走测验(TUGT)评价平衡功能、6分钟步行试验(6MWT)和10米步行试验(10MWT)评价行走能力。结果两组患者训练8周时UPDRSⅢ评分(P=0.000)和TUGT时间(P=0.000)低于训练前,BBS评分(P=0.000)、6MWT时间(P=0.000)和10MWT步速(P=0.000)高于训练前;训练8周时水中组患者UPDRSⅢ评分(P=0.037)和TUGT时间(P=0.013)低于陆上组,BBS评分高于陆上组(P=0.018)。结论常规陆上康复训练和水中运动训练均可以改善帕金森病患者运动功能、平衡功能和行走能力,特别是在运动功能和平衡功能方面水中运动训练效果优于常规陆上康复训练。     

Assuring interrater reliability for the UPDRS motor section: utility of the UPDRS teaching tape.

We assessed rates of successful certification on the motor section of the Unified Parkinson's Disease Rating Scale (UPDRSm) after training with the UPDRS Teaching Tape. The most frequently used clinical scale for PD is the UPDRS, and most clinical trials rely on the motor examination as the primary outcome measure. Whereas the Movement Disorder Society's UPDRS Teaching Tape has been used widely as a training format, outcome data are lacking. We examined data sets from four multicenter studies that required raters to pass the certification exercise of the UPDRS Teaching Tape. Raters viewed the Teaching Tape showing examples of all rating levels for all items (38 minutes), and then took the certification exercise, rating 4 subjects with PD (20 minutes). Certification required scores on all 4 subjects that fit within the 95% confidence interval range established by three experts. We calculated the numbers of raters successfully certified after one or more rating attempts. Only one-half of 226 raters that participated successfully completed certification on their first attempt, but all completed by the third attempt. North American raters scored better than Europeans raters. The most difficult case to rate was the subject with the least impairment. Standardized methods for training UPDRSm application are essential to ensure that raters use the scale uniformly. Raters have the greatest difficulty with the mildest impairment, making training especially important to studies of early PD.     

Randomized trial of safinamide add‐on to levodopa in Parkinson's disease with motor fluctuations

Levodopa is effective for the motor symptoms of Parkinson's disease (PD), but is associated with motor fluctuations and dyskinesia. Many patients require add‐on therapy to improve motor fluctuations without exacerbating dyskinesia. The objective of this Phase III, multicenter, double‐blind, placebo‐controlled, parallel‐group study was to evaluate the efficacy and safety of safinamide, an α‐aminoamide with dopaminergic and nondopaminergic mechanisms, as add‐on to l ‐dopa in the treatment of patients with PD and motor fluctuations. Patients were randomized to oral safinamide 100 mg/day (n = 224), 50 mg/day (n = 223), or placebo (n = 222) for 24 weeks. The primary endpoint was total on time with no or nontroublesome dyskinesia (assessed using the Hauser patient diaries). Secondary endpoints included off time, Unified Parkinson's Disease Rating Scale (UPDRS) Part III (motor) scores, and Clinical Global Impression‐Change (CGI‐C). At week 24, mean ± SD increases in total on time with no or nontroublesome dyskinesia were 1.36 ± 2.625 hours for safinamide 100 mg/day, 1.37 ± 2.745 hours for safinamide 50 mg/day, and 0.97 ± 2.375 hours for placebo. Least squares means differences in both safinamide groups were significantly higher versus placebo. Improvements in off time, UPDRS Part III, and CGI‐C were significantly greater in both safinamide groups versus placebo. There were no significant between‐group differences for incidences of treatment‐emergent adverse events (TEAEs) or TEAEs leading to discontinuation. The addition of safinamide 50 mg/day or 100 mg/day to l ‐dopa in patients with PD and motor fluctuations significantly increased total on time with no or nontroublesome dyskinesia, decreased off time, and improved parkinsonism, indicating that safinamide improves motor symptoms and parkinsonism without worsening dyskinesia. © 2013 International Parkinson and Movement Disorder Society     

The UPDRS-8: a brief clinical assessment scale for Parkinson's disease

We 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.     

Do children with autism and Asperger's disorder have difficulty controlling handwriting size? A kinematic evaluation

Children with autism spectrum disorders (ASD) often show difficulties in controlling letter size and consistent letter formation during handwriting; however, there has been little research into the underlying nature of handwriting impairments in this group. The aim of this study was to assess the ability of children with ASD to regulate the size and consistency of fundamental handwriting movements when using writing guides, and determine whether the kinematic profile during writing is different to typically developing children. Twenty-six boys with ASD (16 with high-functioning autism, 10 with Asperger's disorder) aged 8–13 years (IQ > 75), and 17 typically developing children wrote a series of four cursive letter l's using 10 mm and 40 mm writing guides, using a graphics tablet and stylus. Movement size and consistency was comparable between groups when the writing guides were set at 10 mm; however, handwriting movements of children with ASD were significantly faster and more fluent than typically developing children when writing guides were set at 40 mm. Neuromotor noise was comparable to that of typically developing children across both writing sizes. Clinically, our findings indicate that children with ASD have a well-automated motor plan for simple handwriting movements when writing guides are present and that problems of handwriting legibility in ASD are likely to arise from other factors, such as complex motor chaining (i.e. writing whole words and sentences), or attentional, working memory and linguistic demands when writing.     

Therapeutic effect of repetitive transcranial magnetic stimulation in Parkinson's disease: Analysis of [11C] raclopride PET study

Repetitive transcranial magnetic stimulation (rTMS) has been used as a potential therapeutic tool in Parkinson's disease (PD). However, the therapeutic value and/or the placebo effect of rTMS on PD remain to be elucidated. To investigate the therapeutic value and/or placebo effect of rTMS in PD, we compared the motor section of unified PD rating scale (UPDRS III) and the amount of extracellular dopamine concentration using [¹¹C] raclopride PET before and after two sessions of rTMS in 9 PD patients. During a consecutive 2 days while off‐medication, two series of 15 trains of 5 Hz‐frequency rTMS (intensity, 90% of the resting motor threshold) were applied to the hand area of more severely symptomatic motor cortex (MC). After unilateral rTMS of MC, mean raclopride binding potentials (BPs) were reduced not only in putaminal and caudate areas on the stimulated side (?4.9% and ?6.5%, respectively) (P > 0.05) but also in putaminal and caudate areas of nonstimulated hemispheres (?6.6%, P > 0.05 and ?12.1%, P = 0.049, respectively). UPDRS III scores were significantly decreased (35.0 ± 14.1 to 32.0 ± 13.4, P = 0.049). A reduction of raclopride BP in nonstimulated ventral striatum by unilateral rTMS supports the placebo response during rTMS. © 2007 Movement Disorder Society     

Quantitative measurements of alternating finger tapping in Parkinson's disease correlate with UPDRS motor disability and reveal the improvement in fine motor control from medication and deep brain stimulation.

The Unified Parkinson's Disease Rating Scale (UPDRS) is the primary outcome measure in most clinical trials of Parkinson's disease (PD) therapeutics. Each subscore of the motor section (UPDRS III) compresses a wide range of motor performance into a coarse-grained scale from 0 to 4; the assessment of performance can also be subjective. Quantitative digitography (QDG) is an objective, quantitative assessment of digital motor control using a computer-interfaced musical keyboard. In this study, we show that the kinematics of a repetitive alternating finger-tapping (RAFT) task using QDG correlate with the UPDRS motor score, particularly with the bradykinesia subscore, in 33 patients with PD. We show that dopaminergic medication and an average of 9.5 months of bilateral subthalamic nucleus deep brain stimulation (B-STN DBS) significantly improve UPDRS and QDG scores but may have different effects on certain kinematic parameters. This study substantiates the use of QDG to measure motor outcome in trials of PD therapeutics and shows that medication and B-STN DBS both improve fine motor control.     

帕金森操康复训练的临床疗效观察

目的探讨帕金森健康操对帕金森病患者运动功能和日常生活能力的影响。方法选取2013年4月至2014年7月期间我院收治的帕金森病患者38例。分为两组:治疗组给予临床常规药物治疗及常规康复治疗,并在此基础上教授帕金森健康操,每天2 h;对照组仅给予临床常规药物治疗及常规康复治疗。治疗5月及14月后观察疗效。结果两组治疗5月后UPDRSⅡ评分和UPDRSⅢ评分均较治疗前降低,差异具有统计学意义(P0.05);治疗组在治疗14月后,与治疗前比较降低更加显著(P0.01)。治疗组在治疗14月后与治疗5月后比较也有明显降低,差异具有统计学意义(P0.05)。治疗5月后和治疗14月后治疗组与对照组比较,差异均有统计学意义(P0.05)。结论帕金森健康操能提高帕金森病患者的运动功能,改善患者的日常生活活动能力,特别是长期预后具有较好的临床效果。     

Symptom and gait changes after sensory attention focused exercise vs aerobic training in Parkinson's disease

The current study compared lower‐limb aerobic training and sensory attention focused exercise (PD SAFEx) to a non‐exercise control group with the overall objective of determining which strategy would have a greater benefit for Parkinson's disease (PD) symptoms and gait. PD SAFEx was developed to focus on sensorimotor deficits identified in PD with the aim of increasing sensory feedback and body awareness, while the lower‐limb aerobic training utilized a specially designed semi‐recumbent elliptical device. Intervention groups (PD SAFEx, n = 18; aerobic, n = 13) exercised three times/week for 10–12 weeks, while nonexercise control participants (n = 15) maintained their regular activity level for 12 weeks. Outcome measures included the Unified Parkinson's disease rating scale motor section (UPDRS) administered by a blinded clinician; a posture and gait (PG) score (total of UPDRS items 27–31); the Timed‐Up‐and‐Go (TUG); and spatiotemporal aspects of self‐paced gait. PD SAFEx resulted in an improved UPDRS, PG score, and TUG (reached significance when participants with poor attendance were excluded) but not self‐paced gait. The lower‐limb aerobic training led to increased step length and velocity but had no change to disease severity. Since gait improvements were not combined with symptomatic changes, lower‐limb aerobic exercise may not be optimal for individuals with PD. Conversely, sensory‐based exercise (PD SAFEx) was beneficial, and led to improvement in symptoms and functional movement control. © 2009 Movement Disorder Society     

Efficacy and safety of safinamide as an add-on therapy to L-DOPA for patients with Parkinson's disease: A randomized,double-blind,placebo-controlled,phase II/III study

IntroductionSafinamide is a reversible and selective monoamine oxidase-B (MAO-B) and sodium channel inhibitor with demonstrated efficacy in mid-to late-stage Parkinson's disease (PD) as an adjunct to l-DOPA. This study aimed to confirm the efficacy and safety of safinamide in PD patients with wearing-off.MethodsThis 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study included Japanese PD patients with wearing-off on l-DOPA treatment. Patients were randomized to receive placebo (P), safinamide 50 mg/day (S50), or safinamide 100 mg/day (S100). The primary endpoint was the change from baseline in mean daily ON-time without troublesome dyskinesias (ON-time). Other measures included the changes in mean daily OFF-time, the unified Parkinson's disease rating scale (UPDRS) score, and the PDQ-39 summary index.ResultsA total of 406 subjects were randomized, of whom 349 completed the study. Baseline characteristics were balanced. Differences in the change of mean daily ON-time at Week 24 compared with the P group were 1.39 h (p = 0.0002) in the S50 group and 1.66 h (p < 0.0001) in the S100 group. Changes from baseline in mean daily OFF-time, UPDRS Part II total score (OFF phase), UPDRS Part III total score (ON phase), and UPDRS Part I also showed significant improvements. Adverse events occurred in 58.9%, 60.2%, and 61.4% of the P, S50, and S100 groups, respectively. The most common adverse drug reactions were dyskinesias (2.1%, 8.3%, and 10.6%) and visual hallucinations (1.4%, 3.0%, and 4.5%).ConclusionAs an adjunct to l-DOPA, safinamide safely increased ON-time and improved PD symptoms/signs in PD patients with wearing-off.     

Immediate placebo effect in Parkinson's disease--is the subjective relief accompanied by objective improvement?

BACKGROUND: A recent well-conducted meta-analysis showed that placebo effect is associated with a possible small benefit for subjective outcomes, but has no significant effects on objective outcomes. Objective: Herein, we aimed to investigate the immediate effects of two different types of placebo [placebo pill and sham transcranial magnetic stimulation (TMS)] in Parkinson's disease (PD) patients and compared them to the standard treatment (levodopa) in a proper randomized, double-blind, crossover clinical trial. METHODS: PD patients received three different interventions on different days: levodopa, placebo pill, and sham TMS. The motor function was assessed using simple and choice reaction time, Unified Parkinson's Disease Rating Scale (UPDRS), finger tapping, Purdue Pegboard test, time to button up, walking time and supination-pronation. The subjective motor function was measured by a visual analogue scale (VAS). RESULTS: The results showed that there was a significant motor function in the motor function only after the treatment with levodopa, but not after treatment with placebo pills or sham TMS. However, patients reported a similar subjective improvement in motor function indexed by VAS following these three treatments. CONCLUSION: These results suggest that placebo interventions in PD may have an immediate subjective sensation of improvement but result in no significant objective motor changes compared with levodopa treatment. Although physiological changes are possible after a placebo intervention, our findings suggest that the acute placebo effect in PD may be the result of the subjective change in the motor rating only.     

A randomized, double-blind, placebo-controlled trial of safinamide as add-on therapy in early Parkinson's disease patients

Safinamide is an α-aminoamide with both dopaminergic and nondopaminergic mechanisms of action evaluated as an add-on to dopamine agonist (DA) therapy in early-stage PD. In this 24-week, double-blind study, patients with early PD receiving a stable dose of a single DA were randomized to once-daily safinamide 100 mg, safinamide 200 mg, or placebo. The primary efficacy variable was UPDRS part III (motor examination) total score. Analysis was hierarchical: 200 mg of safinamide versus placebo was tested first; the success of safinamide 100 mg versus placebo was contingent on this. Two hundred sixty-nine patients received safinamide 100 mg (n = 90), safinamide 200 mg (n = 89), or placebo (n = 90); 70, 81, and 81 patients, respectively, completed the study. Mean improvements from baseline to week 24 in UPDRS III total scores were -3.90 for safinamide 200 mg, -6.0 for safinamide 100 mg and -3.60 for placebo. The difference between safinamide 200 mg and placebo was not significant [point estimate: -0.4; 95% confidence interval (CI): -2.3-1.4; P = 0.6504]. Although the difference between 100 mg/day and placebo was significant (point estimate: -1.9; 95% CI: -3.7 to -0.1; P = 0.0419), these results are considered exploratory. No clinically meaningful differences from placebo were observed for any safety variables. This study did not demonstrate a significant improvement of the primary endpoint for safinamide 200 mg/day. Exploratory analysis of the primary endpoint for 100 mg/day demonstrated that the addition of safinamide to a stable dose of DA improves motor symptoms in early PD and warrants further investigation.