Quality of life in early Parkinson's disease treated with levodopa/carbidopa/entacapone

We aimed to investigate whether treatment with levodopa/carbidopa/entacapone when compared with levodopa/carbidopa improves quality of life in Parkinson's disease (PD) patients with no or minimal, nondisabling motor fluctuations. This is a multicenter, randomized, double‐blind study. One hundred eighty‐four patients on 3 to 4 equal doses of 100/25 to 200/50 mg levodopa/carbidopa or levodopa/benserazide, 0 to 3 hours of nondisabling OFF time over a 48 hour period and no dyskinesia were randomized to levodopa/carbidopa/entacapone or levodopa/carbidopa treatment for 12 weeks. The primary outcome measure was quality of life as assessed by the PDQ‐8. Secondary outcome measures were the UPDRS parts I–IV, and the Wearing Off Card. Treatment with levodopa/carbidopa/entacapone resulted in significantly greater improvements in PDQ‐8 scores compared to treatment with levodopa/carbidopa (mean difference 1.4 points, P = 0.021). Statistically significant improvements were seen predominantly in nonmotor domains (depression, personal relationships, communication, stigma, all P < 0.05; dressing P = 0.056). Patients who were randomly assigned to levodopa/carbidopa/entacapone also showed significantly greater improvement in UPDRS part II scores (P = 0.032) with UPDRS part III scores showing borderline significance. Differences in UPDRS parts I and IV and Wearing Off Card scores were not significant. Treatment with levodopa/carbidopa/entacapone results in improved quality of life compared with levodopa/carbidopa in PD patients with mild or minimal, nondisabling motor fluctuations. © 2007 Movement Disorder Society     

Deep Brain Stimulation for Early-Stage Parkinson’s Disease: An Illustrative Case

Objectives: Subthalamic nucleus (STN) deep brain stimulation (DBS) is an effective intervention in advanced Parkinson's disease (PD), but its efficacy and safety in early PD are unknown. We are conducting a randomized pilot trial investigating DBS in early PD. This report describes one participant who received bilateral STN‐DBS. Materials and Methods: Thirty subjects have been randomized to either optimal drug therapy (ODT) or DBS + ODT. Microelectrode recordings from the STN and substantia nigra are collected at implantation. The Unified Parkinson's Disease Rating Scale Motor Subscale (UPDRS‐III) is administered in the ON and OFF states semi‐annually and neuropsychological function and quality of life are assessed annually. We describe a 54‐year‐old man with a two‐year history of PD who was randomized to DBS + ODT and followed for two years. Results: The subject showed a lower STN to substantia nigra ratio of neuronal activity than advanced PD patients, and higher firing rate than non‐PD patients. The subject's total UPDRS and UPDRS‐III scores improved during the two‐year follow‐up, while his OFF UPDRS‐III score and levodopa equivalent daily dose increased. Quality of life, verbal fluency, and verbal learning improved. He did not experience any serious adverse events. Conclusions: This report details the first successful application of bilateral STN‐DBS for early‐stage PD during a clinical trial.     

Repetitive transcranial magnetic stimulation of the primary motor cortex in the treatment of motor signs in Parkinson's disease: A quantitative review of the literature

Parkinson's disease (PD) is a progressive disorder characterized by the emergence of motor deficits. In light of the voluminous and conflicting findings in the literature, the aim of the present quantitative review was to examine the effects of repetitive transcranial magnetic stimulation (rTMS) targeting the primary motor cortex (M1) in the treatment of motor signs in PD. Studies meeting inclusion criteria were analyzed using meta‐analytic techniques and the Unified Parkinson's Disease Rating Scale (UPDRS) sections II and III were used as outcome measures. In order to determine the treatment effects of rTMS, the UPDRS II and III scores obtained at baseline, same day, to 1 day post rTMS treatment (short‐term follow‐up) and 1‐month post stimulation (long‐term follow‐up) were compared between the active and sham rTMS groups. Additionally, the placebo effect was evaluated as the changes in UPDRS III scores in the sham rTMS groups. A placebo effect was not demonstrated, because sham rTMS did not improve motor signs as measured by UPDRS III. Compared with sham rTMS, active rTMS targeting the M1 significantly improved UPDRS III scores at the short‐term follow‐up (Cohen's d of 0.27, UPDRS III score improvement of 3.8 points). When the long‐term follow‐up UPDRS III scores were compared with baseline scores, the standardized effect size between active and sham rTMS did not reach significance. However, this translated into a significant nonstandardized 6.3‐point improvement on the UPDRS III. No significant improvement in the UPDRS II was found. rTMS over the M1 may improve motor signs. Further studies are needed to provide a definite conclusion. © 2015 International Parkinson and Movement Disorder Society     

Intrajejunal levodopa infusion in Parkinson's disease: A pilot multicenter study of effects on nonmotor symptoms and quality of life

Switching from oral medications to continuous infusion of levodopa/carbidopa gel reduces motor complications in advanced Parkinson's disease (PD), but effects on nonmotor symptoms (NMSs) are unknown. In this prospective open‐label observational study, we report the effects of intrajejunal levodopa/carbidopa gel infusion on NMS in PD based on standard assessments utilizing the nonmotor symptoms scale (NMSS) along with the unified Parkinson's disease rating scale (UPDRS 3 motor and 4 complications) and quality of life (QoL) using the Parkinson's disease questionnaire (PDQ‐8). Twenty‐two advanced PD patients (mean age 58.6 years, duration of disease 15.3 years) were followed for 6 months. A statistically significant beneficial effect was shown in six of the nine domains of the NMSS: cardiovascular, sleep/fatigue, attention/memory, gastrointestinal, urinary, and miscellaneous (including pain and dribbling) and for the total score of this scale (NMSST) paralleling improvement of motor symptoms (UPDRS 3 motor and 4 complications in “best on” state) and dyskinesias/motor fluctuations. In addition, significant improvements were found using the Parkinson's disease sleep scale (PDSS) and the PDQ‐8 (QoL). The improvement in PDQ‐8 scores correlated highly significantly with the changes in NMSST, whereas a moderately strong correlation was observed with UPDRS changes. This is the first demonstration that a levodopa‐based continuous dopaminergic stimulation is beneficial for NMS and health‐related quality of life in PD in addition to the reduction of motor fluctuations and dyskinesias. © 2009 Movement Disorder Society     

Motor complications in Parkinson's disease: Ten year follow‐up study

Parkinson's disease (PD) can be symptomatically controlled with standard treatments; however, after a few years, this response typically declines and most patients develop motor complications. We carried out a prospective practice‐based study to evaluate the evolution appearance and evolution of motor complications in 64 de novo PD patients over 5 years and in 38 PD patients over 10 years. We studied untreated patients from initial assessment at basal conditions and evaluated every 6 months thereafter with treatment (levodopa versus other drugs). The follow‐up assessments were performed with the Unified Parkinson's Disease Rating Scale (UPDRS). At each assessment, patients were monitored regarding the development of dyskinesias, motor fluctuations, freezing, loss of postural reflexes, and cognitive impairment. We observed a significant improvement in UPDRS scores during the first year, then a progressive decline, more evident after the third year. Motor complications increased after the third year, and at the end of the survey (tenth year); drug‐induced dyskinesias and motor fluctuations were experienced (71.1 and 94.7%, respectively). After the first decade, many complications arose from the non‐levodopa–responsive features of the disease (cognitive impairment was present in 52.6% and gait freezing in 71.1%). Initial medication may influence medium‐term complications but not long‐term problems. Most long‐term disabling problems of PD were related to non‐levodopa‐responsive features. © 2010 Movement Disorder Society.     

Longitudinal psychometric attributes,responsiveness, and importance of change: An approach using the SCOPA‐Psychosocial questionnaire

The objective of this study was to illustrate the analysis of longitudinal validity, responsiveness, and importance of change, using the SCOPA‐Psychosocial Questionnaire (SCOPA‐PS) as a source of empirical data. Sixty‐seven patients with PD in Hoehn and Yahr (HY) stage 2 were followed up for 1 year and assessed by means of the Schwab and England Scale, Unified PD Rating Scale (UPDRS), Hospital Anxiety and Depression Scale (HADS), PDQ‐39, and SCOPA‐PS. A range of methods was applied to enable each of the target attributes to be analyzed from different conceptual stances. The SCOPA‐PS displayed satisfactory acceptability (no floor or ceiling effect), internal consistency (α = 0.80–0.84), convergent validity (r_S = 0.70–0.82 with PDQ‐39), and precision (SEM = 8.80), both at baseline and at the end of follow‐up. The threshold value for significant change ranged from 17.25 (1.96 SEM) to 24.39 (Smallest real difference and Reliable change index). Threshold values for a clinically meaningful change were 0.73–1.26 (effect size, standardized response mean, responsiveness statistic). Change in SCOPA‐PS scores correlated strongly with change in total UPDRS, HADS, and PDQ‐39 scores, and reliably detected 70% of cases that worsened according to the PDQ‐39. The minimally important change (MIC) for “minimally impaired” patients as per the PDQ39 was 8.30–9.10 points. Indices such as 1.96 SEM, effect size, and correlation with the change in other measures provide useful information about different concepts of responsiveness. The MIC should be determined for each specific setting, using distribution‐ and anchor‐based methods. The SCOPA‐PS showed satisfactory longitudinal attributes and responsiveness in stage‐2 Brazilian patients with PD across 1 year of follow‐up. © 2008 Movement Disorder Society     

Chronic bilateral electrical stimulation of the subthalamic nucleus for the treatment of advanced Parkinson's disease

Preliminary reports in patients with Parkinson's disease (PD) showed that subthalamic nucleus (STN) stimulation was able to reverse parkinsoniam state. Since 1998 we evaluated the safety and the efficacy of STN stimulation in 7 patients affected by advanced PD. All patients were included using CAPIT protocol. Motor functions and quality of life were evaluated, before and after surgery, with UPDRS and PDQ38, respectively. At the 6-month follow-up, the off medication/on stimulation UPDRS motor score improved by 50.6% and the on medication/on stimulation by 20.3%. Motor fluctuations were reduced by 57.2% and dyskinesias by 73.5%. The total D-dopa equivalent daily dose was reduced by 40.7%. PDQ38 ameliorated by 49.9%. We did not observe any perioperatory complication and only mild and tolerable side effects after stimulation.     

Long-term duodenal levodopa infusion in Parkinson’s disease: a 3-year motor and cognitive follow-up study

Duodenal infusion of levodopa/carbidopa gel (Duodopa) is an effective treatment option for advanced Parkinson’s disease (PD). Long-term clinical experience up to 16 years suggests that the safety of this procedure is acceptable, while several observational studies showed that Duodopa reduces motor fluctuations and dyskinesias improving patients’ quality of life (QoL). The aim of this study is to investigate the long-term motor and cognitive outcome of Duodopa treatment in advanced PD patients and its’ impact on the QoL. Twenty-five consecutive PD patients were assessed using the Unified PD rating scale (UPDRS), a battery of neuropsychological tests, and the PD questionnaire (PDQ-39) at baseline and after a mean period of three years of Duodopa treatment. Seventeen out of 25 patients reached the follow-up evaluation; five patients discontinued Duodopa and three patients died of causes unrelated to drug infusion. Duodopa improved motor complications (UPDRS-IV) and quality of life (PDQ-39). A sub-group of subjects (41 %) developed a significant deterioration of cognitive functions over time. The most common adverse events were dislocation and the kinking of the intestinal tube. In conclusion, Duodopa therapy is effective in the long-term treatment of advanced PD patients. Continuous enteral levodopa infusion achieves a reduction of motor fluctuations and dyskinesias improving patients’ QoL, despite the progression of PD motor symptoms and a significant decline in cognitive functions in a sub-group of patients.     

Calibration of unified Parkinson's disease rating scale scores to Movement Disorder Society‐unified Parkinson's disease rating scale scores

The aim of this study was to develop formulas to convert the UPDRS to Movement Disorder Society (MDS)‐UPDRS scores. The MDS‐UPDRS is a revision of the UPDRS with sound clinimetric properties. Reliable formulas to recalculate UPDRS scores into MDS‐UPDRS equivalents are pivotal to the practical transition and definitive adoption of the MDS‐UPDRS. UPDRS and MDS‐UPDRS scores were collected on 875 PD patients. A developmental sample was used to regress UPDRS scores on corresponding MDS‐UPDRS scores based on three H & Y groupings (I/II, III, and IV/V). Regression weighting factors and intercept terms provided formulas for UPDRS conversions to be tested in a validation sample. Concordance between the true MDS‐UPDRS Part scores and those derived from the formulas was compared using Bland‐Altman's plots and Lin's concordance coefficient (LCC). Significant concordance between UPDRS‐estimated MDS‐UPDRS scores was achieved for Parts II (Motor Experiences of Daily Living) (LCC = 0.93) and III (Motor Examination) (LCC = 0.97). The formulas resulted in mean differences between the true MDS‐UPDRS and estimated MDS‐UPDRS scores of less than 1 point for both Parts II and III. Concordance was not achieved for Parts I and IV (Non‐motor Experiences of Daily Living and Complications of Therapy). Formulas allow archival UPDRS Parts II and III individual patient data to be accurately transferred to MDS‐UPDRS scores. Because Part I collects data on much more extensive information than the UPDRS, and because Part IV is structured differently in the two versions, old ratings for these parts cannot be converted. © 2012 Movement Disorder Society     

Movement Disorder Society Unified Parkinson Disease Rating Scale experiences in daily living: Longitudinal changes and correlation with other assessments

The Movement Disorder Society (MDS) commissioned a revision of the UPDRS with the goals of improving instructions and definitions, more accurately evaluating milder features, and assessing patient‐reported outcomes and nonmotor features. To date, no study has evaluated longitudinal changes in components of the MDS‐UPDRS over time or correlated these with changes in other scales of various symptoms. We assessed Parts I and II of the MDS‐UPDRS (non‐Motor and Motor Experiences of Daily Living [nM‐EDL, M‐EDL]) as well as a number of other scales of motor, cognitive and behavioral function in a large population of patients (n = 383) with early‐ to mid‐stage Parkinson's disease (PD) who had previously participated in a trial of a putative disease‐modifying agent. Both parts of a MDS‐UPDRS showed significant change over the 3‐year follow‐up period, with M‐EDL scores declining to a greater extent than nM‐EDL. Both the scores and their changes over time correlated relatively well with other rating scales of similar disease aspects. Modest correlations with the original version of the UPDRS supported the increased attention to nonmotor symptoms as well as milder levels of severity in the MDS‐UPDRS. The M‐EDL was much more sensitive to change over time in these early‐ to mid‐stage patients than the original UPDRS Activities of Daily Living (ADL) scale. Finally, we showed no change over time in a small group of individuals with dopamine transporter single‐photon emission computed tomography scans without evidence for dopamine deficiency. The nM‐EDL and M‐EDL components of the MDS‐UPDRS provide an effective, relevant measure of change in the broad spectrum of symptoms of PD over the first decade of the disease. © 2013 International Parkinson and Movement Disorder Society     

Comparing exercise in Parkinson's disease—the Berlin BIG Study

Physiotherapy is widely used in Parkinson's disease (PD), but there are few controlled studies comparing active interventions. Recently, a technique named “LSVT®BIG” has been introduced. LSVT®BIG is derived from the Lee Silverman Voice Treatment and focuses on intensive exercising of high‐amplitude movements. In the present comparative study, 60 patients with mild to moderate PD were randomly assigned to receive either one‐to‐one training (BIG), group training of Nordic Walking (WALK), or domestic nonsupervised exercises (HOME). Patients in training (BIG) and WALK received 16 hours of supervised training within 4 (BIG) or 8 (WALK) weeks. The primary efficacy measure was difference in change in Unified Parkinson's Disease Rating Scale (UPDRS) motor score from baseline to follow‐up at 16 weeks between groups. UPDRS scores were obtained by blinded video rating. ANCOVA showed significant group differences for UPDRS‐motor score at final assessment (P < 0.001). Mean improvement of UPDRS in BIG was ?5.05 (SD 3.91) whereas there was a mild deterioration of 0.58 (SD 3.17) in WALK and of 1.68 (SD 5.95) in HOME. LSVT®BIG was also superior to WALK and HOME in timed‐up‐and‐go and timed 10 m walking. There were no significant group differences for quality of life (PDQ39). These results provide evidence that LSVT®BIG is an effective technique to improve motor performance in patients with PD. © 2010 Movement Disorder Society     

Movement Disorder Society‐sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS‐UPDRS): Scale presentation and clinimetric testing results

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 = 0.79–0.93 across parts) and correlated with the original UPDRS (ρ = 0.96). MDS‐UPDRS across‐part 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     

A randomized controlled trial of patient‐reported outcomes with tai chi exercise in Parkinson's disease

A previous randomized, controlled trial of tai chi showed improvements in objectively measured balance and other motor‐related outcomes in patients with Parkinson's disease. This study evaluated whether patient‐reported outcomes could be improved through exercise interventions and whether improvements were associated with clinical outcomes and exercise adherence. In a secondary analysis of the tai chi trial, patient‐reported and clinical outcomes and exercise adherence measures were compared between tai chi and resistance training and between tai chi and stretching exercise. Patient‐reported outcome measures were perceptions of health‐related benefits resulting from participation, assessed by the Parkinson's Disease Questionnaire (PDQ‐8) and Vitality Plus Scale (VPS). Clinical outcome measures included motor symptoms, assessed by a modified Unified Parkinson's Disease Rating Scale–Motor Examination (UPDRS‐ME) and a 50‐foot speed walk. Information on continuing exercise after the structured interventions were terminated was obtained at a 3‐month postintervention follow‐up. Tai chi participants reported significantly better improvement in the PDQ‐8 (?5.77 points, P = 0.014) than did resistance training participants and in PDQ‐8 (?9.56 points, P < 0.001) and VPS (2.80 points, P = 0.003) than did stretching participants. For tai chi, patient‐reported improvement in the PDQ‐8 and VPS was significantly correlated with their clinical outcomes of UPDRS‐ME and a 50‐foot walk, but these correlations were not statistically different from those shown for resistance training or stretching. However, patient‐reported outcomes from tai chi training were associated with greater probability of continued exercise behavior than were either clinical outcomes or patient‐reported outcomes from resistance training or stretching. Tai chi improved patient‐reported perceptions of health‐related benefits, which were found to be associated with a greater probability of exercise adherence. The findings indicate the potential of patient perceptions to drive exercise behavior after structured exercise programs are completed and the value of strengthening such perceptions in any behavioral intervention.     

Effectiveness of multidisciplinary care for Parkinson's disease: A randomized,controlled trial

Multidisciplinary care is considered an optimal model to manage Parkinson's disease (PD), but supporting evidence is limited. We performed a randomized, controlled trial (RCT) to establish whether a multidisciplinary/specialist team offers better outcomes, compared to stand‐alone care from a general neurologist. Patients with PD were randomly allocated to an intervention group (care from a movement disorders specialist, PD nurses, and social worker) or a control group (care from general neurologists). Both interventions lasted 8 months. Clinicians and researchers were blinded for group allocation. The primary outcome was the change in quality of life (Parkinson's Disease Questionnaire; PDQ‐39) from baseline to 8 months. Other outcomes were the UPDRS, depression (Montgomery‐Asberg Depression Scale; MADRS), psychosocial functioning (Scales for Outcomes in Parkinson's disease‐Psychosocial; SCOPA‐PS), and caregiver strain (Caregiver Strain Index; CSI). Group differences were analyzed using analysis of covariance adjusted for baseline values and presence of response fluctuations. A total of 122 patients were randomized and 100 completed the study (intervention, n = 51; control, n = 49). Compared to controls, the intervention group improved significantly on PDQ‐39 (difference, 3.4; 95% confidence interval [CI]: 0.5–6.2) and UPDRS motor scores (4.1; 95% CI: 0.8–7.3). UPDRS total score (5.6; 95% CI: 0.9–10.3), MADRS (3.7; 95% CI: 1.4–5.9), and SCOPA‐PS (2.1; 95% CI: 0.5–3.7) also improved significantly. This RCT gives credence to a multidisciplinary/specialist team approach. We interpret these positive findings cautiously because of the limitations in study design. Further research is required to assess teams involving additional disciplines and to evaluate cost‐effectiveness of integrated approaches. © 2012 Movement Disorder Society     

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     

Fluctuating functions related to quality of life in advanced Parkinson disease: effects of duodenal levodopa infusion

Objective – To assess fluctuations in quality of life (QoL) and motor performance in patients with advanced Parkinson disease (PD) treated with continuous daytime duodenal levodopa/carbidopa infusion or conventional therapy. Methods – Of 18 patients completing a 6‐week trial (DIREQT), 12 were followed for up to 6 months and assessed using electronic diaries and the PD Questionnaire‐39 (PDQ‐39). Results – During the trial and follow‐up, major diurnal fluctuations were observed, especially for hyperkinesia, ‘off’ time, ability to walk and depression. Duodenal infusion was associated with significantly more favourable outcomes compared with conventional treatment for satisfaction with overall functioning, ‘off’ time and ability to walk, with improved outcomes with PDQ‐39. Conclusions – Relative to conventional treatment, infusion therapy may stabilize and significantly improve motor function and patient’s QoL. The potential for daily fluctuation in PD symptoms means single measures of treatment effectiveness can result in bias in effect estimates and hence repeated measures are recommended.     

The effect of deprenyl washout in patients with long-standing Parkinson's disease

Summary. Deprenyl, an irreversible MAO-B inhibitor, is known to have a symptomatic effect in de novo patients with Parkinson's disease (PD). It has, however, not been studied thoroughly in patients with advanced PD and response fluctuations. This study evaluated the effect of washout of deprenyl in patients with long-standing PD. Eleven PD patients who were on chronic treatment with deprenyl (mean age 57 ± 8 years, mean disease duration 8.4 ± 2.9 years), seven with response fluctuations, were enrolled in a double-blind study of a novel MAO-B inhibitor. A deprenyl washout period of one month was required prior to initiation of treatment with the trial drug. Patients were evaluated by Unified Parkinson's Disease Rating scale (UPDRS) before and one month after the washout period. Motor function was quantified by computerized tapping speed and movement time test. Results showed that neither total UPDRS scores (22 ± 16 vs. 18 ± 16, respectively) nor tapping speed and movement time changed significantly (4.4 ± 0.5 vs. 4.2 ± 0.3 Hz and 159 ± 45 vs. 161 ± 40 seconds; p > 0.1, respectively). However, eight patients reported various degrees of subjective deterioration, among them were the seven fluctuating patients. Two patients first began to experience response fluctuations during the washout period. It seems that deprenyl has a symptomatic effect, especially in patients with response fluctuations, and it may postpone the appearance of fluctuations in patients with PD. Attempts to discontinue treatment with deprenyl may aggravate disease symptoms. Received October 26, 2001; accepted January 30, 2002     

Nonmotor symptoms are independently associated with impaired health‐related quality of life in Chinese patients with Parkinson's disease

We performed a cross‐sectional study of 82 Chinese patients with Parkinson's disease (PD) enrolled during an 18‐month period using a clinical interview to assess the prevalence of nonmotor symptoms (NMS), the association with disease severity and motor status, and the impact on patients' health‐related quality of life (Hr‐QoL). The patients' NMS, Hr‐QoL, disease severity, and motor status were assessed by the Nonmotor Symptoms Scale (NMSS), the 39‐item Parkinson's Disease Questionnaire (PDQ‐39), the modified Hoehn and Yahr staging scale (H&Y) and the Unified Parkinson's Disease Rating Scale part III (UPDRS III), respectively. We found that 100% of patients with PD presented with NMS. The NMSS significantly correlated with disease duration (Spearman's r_S = 0.276, P = 0.012), H&Y (r_S = 0.230, P = 0.038), and UPDRS III (r_S = 0.350, P = 0.001). Similarly, the PDQ‐39 SI significantly associated with the disease duration (r_S = 0.258, P = 0.019), H&Y (r_S = 0.340, P = 0.002), and UPDRS III (r_S = 0.453, P < 0.001). NMS domains that influenced the PDQ‐39 SI were sleep/fatigue, mood, gastrointestinal, urinary, and miscellaneous symptoms. This strongly suggested that the five domains played a key role in the manifestation of Hr‐QoL. NMSS explains more of the variability in Hr‐QoL than UPDRS III, when both are the model (stepwise multiple linear regression analysis R² change, 47.8% vs. 5.87%, respectively). Therefore, these findings demonstrate that NMS are independently and negatively associated with Hr‐QoL in PD and that improving NMS should be viewed as an important part in the management of PD. © 2010 Movement Disorder Society     

Motor changes during sertraline treatment in depressed patients with Parkinson’s disease*

Background: Pharmacological interventions to treat depressive symptoms associated with Parkinson’s disease (PD) are limited. Whether selective serotonine re‐uptake inhibitors increase parkinsonism or have clinically significant interactions with antiparkinsonian drugs is unresolved. Purpose: We used a naturalistic approach to prospectively investigate the long‐term effects on motor status of adding sertraline in a large sample of community‐dwelling PD patients with depressive symptoms. Methods: Main outcome measure was the motor part of the Unified PD Rating Scale (UPDRS) at baseline and at 1‐, 3‐, and 6‐month follow‐up. Secondary measures were the change in antiparkinsonian drugs expressed as total levodopa equivalent dose and the scores of the Hospital Anxiety and Depression Scale (HADS). Of the 374 patients included, 310 (82%) completed the study. Results: Treatment with sertraline (mean dose 66.0 ± 29.8 mg) resulted in improvement in all UPDRS domains along with a significant decrease of the HADS scores. A modest but significant increase of the total dose of levodopa, without significant change of total levodopa equivalent dose, was observed. Almost 8% of patients discontinued medication for adverse events, mainly related to the gastrointestinal system. Conclusions: Although worsening of tremor was observed in some patients, active management of depression with sertraline appears to have a positive impact on parkinsonism.     

Nonmotor symptoms evolution during 24 months of bilateral subthalamic stimulation in Parkinson's disease

Background: The objective of this study was to investigate 24‐month of effects of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) on nonmotor symptoms in Parkinson's disease (PD). Methods: In this prospective, observational, multicenter, international study including 67 PD patients undergoing bilateral STN‐DBS, we examined the Non‐motor Symptom Scale, Non‐Motor Symptoms Questionnaire, Parkinson's Disease Questionnaire‐8, Scales for Outcomes in Parkinson's Disease‐motor examination, ‐activities of daily living, and ‐complications, and levodopa‐equivalent daily dose preoperatively and at 5 and 24‐month of follow‐up. After checking distribution normality, longitudinal outcome changes were investigated with Friedman tests or repeated‐measures analysis of variance and Bonferroni correction for multiple comparisons using multiple tests. Post hoc, Wilcoxon signed rank t tests were computed to compare visits. The strength of clinical responses was analyzed using effect size. Explorative Spearman correlations of change scores from baseline to 24‐month follow‐up were calculated for all outcomes. Results: The Non‐motor Symptom Scale and all other outcome parameters significantly improved from baseline to the 5‐month follow‐up. From 5 to 24‐month, partial decrements in these gains were found. Nonetheless, comparing baseline with 24‐month follow‐up, significant improvements were observed for the Non‐motor Symptom Scale (small effect), Scales for Outcomes in PD‐motor examination showed a moderate effect, and Scales for Outcomes in Parkinson's Disease‐complications and levodopa‐equivalent daily dose showed large effects. Non‐motor Symptom Scale change scores from baseline to 24‐month follow‐up correlated significantly with Parkinson's Disease Questionnaire‐8, Scales for Outcomes in Parkinson's Disease‐activities of daily living, and ‐motor complications change scores. Conclusions: This study provides evidence of beneficial effects of bilateral STN‐DBS on nonmotor symptoms at 24‐month follow‐up. The extent of nonmotor symptom improvement was directly proportionate to improvements in quality of life, activities of daily living, and motor complications. This study underlines the importance of nonmotor symptoms for holistic assessments of DBS outcomes. © 2018 International Parkinson and Movement Disorder Society