MDS-UPDRS to assess non-motor symptoms after STN DBS for Parkinson's disease

Objective: To determine if the non-motor sections of the Movement Disorder Society's (MDS) version of the Unified Parkinson's Disease Rating Scale (UPDRS) could supplement the original UPDRS as a patient completed assessment of changes in non-motor symptoms in Parkinson's disease (PD) patients after bilateral subthalamic nucleus (STN) deep brain stimulation (DBS). Methods: Thirty PD patients who underwent bilateral STN DBS were assessed using the total UPDRS and the non-motor sections of the MDS-UPDRS prior to surgery and one year following surgery. This study focuses on non-motor symptoms as assessed by Part I of the UPDRS and Part 1A and 1B of the MDS-UPDRS. Results: One year following surgery, no individual non-motor symptoms or the total mentation score of the UPDRS were significantly changed. In comparison, the MDS-UPDRS showed significant improvements in sleep and urinary problems and a trend towards improvement in anxiety, constipation, daytime sleepiness, fatigue and pain. Conclusions: This study provides evidence that the MDS-UPDRS non-motor sections, when completed by the patients, can supplement the original version of the UPDRS as an effective method of measuring changes in non-motor symptoms after DBS. It also reinforces the benefits of bilateral STN DBS on non-motor symptoms of PD.     

Long-term effect of bilateral STN-DBS on non-motor symptoms in Parkinson's disease: A four-year observational,prospective study

BackgroundSeveral studies have shown beneficial effects of bilateral stimulation of the subthalamic nucleus (STN-DBS) on motor as well as on non-motor symptoms (NMS) up to 36 months post-surgery in advanced Parkinson's disease (PD) patients. We set to explore the long-term effect of STN-DBS on NMS in a four-year follow-up, prospective, observational study.MethodsForty patients were enrolled and assessed at baseline. Twenty-eight were followed-up at 6, 12, 24, 36 and 48 months after the operation. The effect of post-operative time on NMS was analyzed by six-level repeated measures ANOVA. In a post-hoc analysis the follow-up scores were compared to baseline using a paired t-test.ResultsThe following scores stayed improved up to 24 months after surgery, presented as baseline/24 months, p-value (t-test): total Non-Motor Symptoms Scale score (54.0 ± 5.6/44.9 ± 5.0, p = 0.029), Hamilton Anxiety Scale (14.3 ± 1.3/11.3 ± 1.2, p = 0.019) and PDQ39 (53.4 ± 4.5/40.2 ± 2.9, p = 0.012). PD Sleep Scale 2 remained improved throughout the study (17.4 ± 2.0/12.8 ± 1.3 at 48 months, p = 0.032), while Beck Depression Inventory only at six months post-surgery (9.5 ± 1.2/6.7 ± 0.7 at 6 months, p = 0.006). Montreal Cognitive Assessment remained stable up to 24 months and then declined at 36 months (26.3 ± 0.5/25.4 ± 0.5 at 36 months, p = 0.003), Starkstein Apathy Scale deteriorated throughout the study (7.6 ± 0.7/12.7 ± 0.9 at 48 months, p = 0.006).ConclusionsWe observed beneficial effect of STN-DBS in several but not all domains of NMS at least up to 24 months post-op in advanced PD. Further long-term studies on larger cohorts of PD patients and longer follow-up need to be conducted to better understand the long-term effect of STN-DBS on NMS.     

Subcutaneous apomorphine and non-motor symptoms in Parkinson's disease

Non-motor symptoms (NMS) are now recognized to occur across all stages of Parkinson's disease (PD) and as a result there has been an increasing focus on their diagnosis, quantification and effective management. While in some subjects, NMS may be present before diagnosis, in advanced PD, NMS can contribute to hospitalization, severe disability and a shortened life expectancy. Strategies for continuous drug delivery have been reported to have a beneficial effect on NMS in PD and while the efficacy of apomorphine on motor function in PD has been confirmed in a number of studies, in addition to its possible anti-dyskinetic effect, a number of reports have also outlined the possible beneficial effect of apomorphine on NMS. This review sets out to examine the efficacy of apomorphine in non-motor aspects of PD, including its effect on neuropsychiatric and gastrointestinal symptoms, sleep (including restless legs syndrome), urinary dysfunction, pain and impulse control disorders. The analysis takes into consideration case reports, and open-label and comparative case–control studies published to date. Results of this review suggest that although data on the effect of apomorphine on NMS in PD patients are limited there is a strong suggestion of a beneficial effect that warrants further investigation in double-blind studies.     

早期初诊帕金森病患者非运动症状的研究

目的探讨早期帕金森病(PD)患者不同年龄分组、不同临床亚型非运动症状(NMS)的特点。方法收集门诊首次就诊且发病在1年内的早期PD患者96例和正常对照者102例,调查临床资料及相关量表并进行比较。结果 91例(93.83%)患者至少出现1项NMS,常见症状依次为近记忆力下降(70.83%,68例)、便秘(48.96%,47例)、注意力下降(47.92%,46例),比例均高于对照组(均P0.01)。年龄≤60岁较年龄60岁感焦虑害怕或恐慌的发生率明显升高(P0.01);强直型尿急的发生率明显高于震颤型(P0.01)。结论早期PD患者非运动症状复杂多样。不同年龄组及不同临床亚型NMS的表现也有所差异。     

帕金森病患者非运动症状波动的临床特点

目的探讨帕金森病(PD)患者非运动症状波动的临床特点。方法采用剂末现象问卷(WOQ-19)评价121例原发性PD患者的运动症状波动和非运动症状波动,并采用视觉模拟评分法(VAS)对WOQ-19的每一项症状进行量化。采集患者的一般信息及服药情况,同时采用统一PD评定量表Ⅲ(UPDRSⅢ)和Hoehn-Yahr量表(H-Y分级)评价患者运动功能及对进行病程分级。结果 121例PD患者中,114例(94.2%)有非运动症状,其中44例(38.6%)有非运动症状波动。非运动症状中,焦虑、情绪低落/思维迟钝、情绪变化的发生率较高。在非运动症状波动中,焦虑、情绪变化、多汗、情绪低落/思维迟钝的症状波动发生率较高。神经精神性症状波动发生率(42.3%)显著高于自主神经性症状(27.9%)与感觉性症状(23.4%)(均P0.05)。患者焦虑、情绪变化、情绪低落/思维迟钝、多汗、疼痛、酸痛、麻木、腹部不适感的VAS评分在服药后明显降低(均P0.05)。非运动症状波动患者病程、服药年限、H-Y分级、UPDRSⅢ开期及关期评分、复方左旋多巴剂量及左旋多巴等效剂量均显著高于无波动患者(均P0.05)。兼有运动症状、非运动症状波动患者UPDRSⅢ关期评分及左旋多巴等效剂量均明显高于单纯运动症状波动患者(均P0.05)。结论 PD患者非运动症状波动发生率约40%,神经精神性非运动症状波动更频繁。非运动症状波动与病程及服药年限长,H-Y分级、UPDRSⅢ评分及左旋多巴等效剂量高,同时兼有运动症状波动等因素有关。     

Influence of istradefylline on non-motor symptoms of Parkinson's disease: A subanalysis of a 1-year observational study in Japan (J-FIRST)

IntroductionThe non-motor symptoms (NMSs) of Parkinson's disease (PD) significantly impact the patient's health-related quality of life. This subanalysis of the J-FIRST study evaluated the effect of istradefylline, a selective adenosine A_2A receptor antagonist, on NMSs in istradefylline-naïve Japanese patients with PD.MethodsPatients with PD and ≥1 NMS and ‘wearing-off’ with their current antiparkinsonian treatment were observed for up to 52 weeks. The effect of istradefylline on NMSs was measured in terms of changes in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part 1 total, individual sub-items scores and the 8 item PD questionnaire (PDQ-8) estimated by the marginal structural model.ResultsOverall, 732 patients were istradefylline-naïve prior to the study, of whom 171 were treated with istradefylline for ≥8 weeks during the observation period (istradefylline-treated patients). At baseline, istradefylline-treated patients were more likely to have a dyskinesia (49.7% vs 40.8%) and received a significantly higher daily dose of levodopa (462.8 mg vs 413.0 mg) than those who did not receive istradefylline (n = 561). MDS-UPDRS Part 1 total score at the end of the 52-week observational period slightly increased in patients who received istradefylline and those who did not (0.49 ± 0.41 vs 0.07 ± 0.20; P = 0.36). There were no statistically significant differences between the two groups of patients in terms of changes in the MDS-UPDRS Part 1 total score or any sub-items, or in the PDQ-8 total score.ConclusionNMSs remained generally controlled in istradefylline-treated Japanese patients with PD who exhibited wearing-off with their current antiparkinsonian treatment. Istradefylline could be a feasible treatment option for patients with advanced PD, without worsening existing NMSs.     

Quantitation of non-motor symptoms in Parkinson's disease

Background:  Disabling non-motor symptoms (NMS) associated with Parkinson's disease (PD), such as dementia and loss of balance, do not respond well to levodopa therapy and can lead to eventual death in patients with the disease. In 2006, a multidisciplinary group of experts and patient representatives developed an NMS screening questionnaire (NMSQuest) and a unified Non-Motor Symptoms Scale (NMSS) to address the need for simple identification and comprehensive assessment of NMS in patients with PD.
Methods and Results:  An international pilot study of 96 healthy controls and 123 patients with various stages of treated and untreated PD was conducted to demonstrate that the NMSQuest is a feasible, valid, and accepted tool.
Conclusion:  The majority of patients and caregivers felt that the questionnaire was clear and relevant to their daily lives. Data from 242 PD patients with no dementia were analysed in a pilot study on the clinimetric validation of NMSS. Similar to the NMSQuest study, the NMSS study revealed a significant correlation between progression of PD and increasing NMS burden. These studies suggest that the NMSQuest accurately detects the NMS, and that the NMSS closely correlates with quality of life for PD patients.     

Response of non-motor symptoms to levodopa in late-stage Parkinson's disease: Results of a levodopa challenge test

BackgroundNon-motor symptoms (NMS) are extremely common among late-stage Parkinson's disease (LSPD) patients. Levodopa (L-dopa) responsiveness seems to decrease with disease progression but its effect on NMS in LSPD still needs to be investigated.ObjectiveTo assess the response of blood pressure (BP), pain, fatigue and anxiety to L-dopa in LSPD patients.Methods20 LSPD patients, defined as Schwab and England ADL Scale <50 or Hoehn Yahr Stage >3 (MED ON) and 22 PD patients treated with subthalamic deep brain stimulation (advanced PD group) underwent an L-dopa challenge. BP and orthostatic hypotension (OH) assessment, a visual analogue scale (VAS) for pain and fatigue and the Strait Trait Anxiety (STAI) were evaluated before and after the L-dopa challenge.ResultsSystolic BP dropped significantly after L-dopa intake (p < 0.05) in LSPD patients, while there was no change in pain, fatigue or anxiety. L-dopa significantly improved (p < 0.05) pain and anxiety in the advanced PD group, whereas it had no effect on BP or fatigue. L-dopa-related adverse effects (AEs), namely OH and sleepiness, were more common among LSPD patients. 40% and 65% of LSPD patients were not able to fill out the VAS and the STAI, respectively, while measurement of orthostatic BP was not possible in four LSPD patients.ConclusionsThis exploratory study concludes that some non-motor variables in LSPD do not benefit from the acute action of L-dopa while it can still induce disabling AEs. There is a need for assessment tools of NMS adapted to these disabled LSPD patients.     

The association between non-motor symptoms in Parkinson's disease and age at onset

Objective

Age at onset is likely to be related to a wide range of problems in Parkinson's disease (PD), including cardinal motor features, motor complications and non-motor symptoms (NMS). This study investigated the effect of the age at onset on NMS.

Methods

Two hundred and thirty patients were examined and classified into one of three groups based on age at onset: early onset PD (EOPD) group (<45 years), middle-age onset group (45–64 years) and old-age onset group (≥65 years). The trends relating to NMS were compared across the three groups. The EOPD and old-age onset groups were separately studied to determine their association to the appearance of non-motor features using logistic regression analysis.

Results

There were upward trends in the occurrence of dribbling (P = 0.009; all P values are stated for trend), impaired taste/smelling (P = 0.016), constipation (P = 0.006), urinary urgency (P = 0.002), nocturia (P = 0.018), hallucinations (P = 0.016) and acting out during dreams (P = 0.011) with the increase of age at onset. Older age at onset is an independent risk factor for dementia (OR = 8.42, CI 3.16–22.44), dribbling (OR = 4.14, CI 1.93–8.87), impaired taste/smelling (OR = 2.23, CI 1.20–4.13), constipation (OR = 3.42, CI 1.88–6.24), incomplete bowel emptying (OR = 2.23, CI 1.19–4.20), urinary urgency (OR = 2.58 CI 1.46–4.57), nocturia (OR = 2.65, CI 1.49–4.71), hallucinations (OR = 5.32, CI 1.78–15.97), dizziness (OR = 3.03, CI 1.59–5.79), falling (OR = 3.60, CI 1.67–7.77), insomnia (OR = 2.29, CI 1.28–4.11), intense vivid dreaming (OR = 2.10, CI 1.21–3.66) and acting out during dreams (OR = 2.23, CI 1.24–4.01).

Conclusions

PD patients with different ages at onset present clinically different symptoms in terms of NMS. Old-age onset PD is characterized by more olfactory and sensory symptoms, autonomic symptoms, sleep disorders, dementia and psychosis compared to EOPD.     

Rotigotine and specific non-motor symptoms of Parkinson's disease: Post hoc analysis of RECOVER

BackgroundNon-motor symptoms of Parkinson's disease (PD) represent major causes of morbidity. RECOVER, a randomized controlled trial of rotigotine transdermal system, was the first prospective controlled trial to use the Non-Motor Symptoms Scale (NMSS) as an exploratory outcome for assessment of treatment effects on non-motor symptoms in PD. Rotigotine improved NMSS total score compared with placebo, and the “Sleep/fatigue” and “Mood/apathy” domains. This post hoc analysis further characterizes the effects of rotigotine on sleep/fatigue and mood/apathy.MethodsPatients with PD and unsatisfactory early-morning motor impairment were randomized to transdermal patches of rotigotine (2–16 mg/24 h) or placebo. Treatment was titrated to optimal dose over 1–8 weeks, maintained for 4 weeks. The NMSS was assessed at baseline and end of treatment. Post hoc analyses are presented for individual items of the “Sleep/fatigue” and “Mood/apathy” domains. The interpretation of p-values is considered exploratory in nature.ResultsOf 287 patients randomized, NMSS data were available for 267 patients (178 rotigotine, 89 placebo). Within the “Sleep/fatigue” domain there was a significant difference, in favor of rotigotine, in change from baseline score in 1 of 5 items: “fatigue (tiredness) or lack of energy” (ANCOVA, p < 0.0001). Within the “Mood/apathy” domain, there were significant differences in favor of rotigotine in 4 of 7 items: “lost interest in surroundings” (p < 0.0001), “lost interest in doing things” (p < 0.0001), “seems sad or depressed” (p < 0.01), and “difficulty experiencing pleasure” (p < 0.05).ConclusionsRotigotine transdermal system may improve non-motor symptoms such as fatigue, symptoms of depression, anhedonia, and apathy in patients with PD; further prospective controlled studies are required to confirm this post hoc analysis.     

The impact of non-motor symptoms on the Health-Related Quality of Life of Parkinson's disease patients from Southwest China

BackgroundThe impact of non-motor symptoms (NMS) on the Health-Related Quality of Life (HRQoL) of patients with Parkinson's disease (PD) in the Chinese population are largely unknown.ObjectivesTo study the impact of NMS on the HRQoL in Chinese PD patients.MethodsA total of 693 PD patients from Southwest China were included in the study. NMS of patients were evaluated by non-motor symptoms scale (NMSS) and Parkinson's disease questionnaire-39 item version (PDQ-39) was used to evaluate the HRQoL of PD.ResultsThe mean total score of NMSS was 37.2 ± 33.0 and the most prevalent NMS domain was sleep/fatigue (79.8%). There was a significant strong positive correlation between total NMSS score (r_s = 0.71, P < 0.01), sleep/fatigue domain (r_s = 0.60, P < 0.01) and PDQ-39 SI. Mood/apathy (r_s = 0.55, P < 0.01), attention/memory (r_s = 0.42, P < 0.01), gastrointestinal (r_s = 0.44, P < 0.01) and Miscellany domains (r_s = 0.46, P < 0.01) moderately correlated with PDQ-39 SI. A strong correlation was found between PDQ-39 SI (r_s = 0.71, P < 0.01), emotional well-being (r_s = 0.62, P < 0.01), cognitions (r_s = 0.62, P < 0.01), and the total score of NMSS. Moderate correlation was found between mobility (r_s = 0.45, P < 0.01), activities of daily living (r_s = 0.43, P < 0.01), stigma (r_s = 0.42, P < 0.01), communication (r_s = 0.47, P < 0.01), bodily discomfort (r_s = 0.46, P < 0.01) and the total score of NMSS. Female, H–Y stage, UPDRS-III and NMSS total score were the potential determinants of worse HRQoL of PD patients.ConclusionsNMS have close association with various aspects of the HRQoL. Severe NMS may be related to dramatic decline of the HRQoL of PD patients.     

Rotigotine transdermal patch in early Parkinson's disease: a randomized, double-blind, controlled study versus placebo and ropinirole.

Rotigotine is a new, non-ergot dopamine agonist formulated in a transdermal delivery system. The present study was to investigate the efficacy and safety of the rotigotine transdermal patch in the treatment of early Parkinson's disease. Patients (n = 561) were randomized to rotigotine, ropinirole, or placebo. The titration period was up to 13 weeks, and there was a minimum dose-maintenance period of 24 weeks for ropinirole and 33 weeks for rotigotine. The primary endpoint was the proportion of patients with a minimum of 20% decrease in the combined Unified Parkinson's Disease Rating Scale Part II and Part III scores. The responder rate in the rotigotine group was significantly higher than in the placebo group (52% vs. 30%, P < 0.0001). Transdermal rotigotine at doses < or =8 mg/24 h did not show noninferiority to ropinirole at doses < or =24 mg/day. In a post-hoc subgroup analysis, rotigotine < or =8 mg/24 hours had a similar efficacy to ropinirole at doses < or =12 mg/day. The rotigotine transdermal patch was well tolerated. The most common adverse events were application-site reactions, nausea, and somnolence. Application-site reactions were predominantly mild or moderate in intensity. In conclusion, the rotigotine transdermal patch represents an effective and safe option for the treatment of patients with early Parkinson's disease.     

Relationship between sleep disorders and other non-motor symptoms in Parkinson's disease

BackgroundThe association between sleep disorders and other non-motor symptoms (NMS) in Parkinson's disease (PD) has been scarcely investigated.ObjectiveTo describe the prevalence of insomnia and hypersomnia in PD and analyze their relationship with other NMS.MethodsCross-sectional, multicenter study including 388 PD patients evaluated with Hoehn and Yahr, Clinical Impression of Severity Index for PD, Scales for Outcomes in Parkinson's Disease (SCOPA)-Sleep(S), SCOPA-Cognition, SCOPA-Psychiatric Complications, SCOPA-Autonomic, Hospital Anxiety and Depression Scale, and fatigue and pain visual analogue scales. Spearman correlation coefficients, Mann–Whitney test and multiple linear regression analysis were applied.ResultsMean age (54% male) was 65.9 ± 11.2 years old, with disease duration of 8.1 ± 6.0 years and median HY = 2 (range: 1–5). Mean SCOPA-S nocturnal sleep (NS) was 5.4 ± 4.0 (range: 0–15), daytime sleepiness (DS) was 3.76 ± 3.04 (range: 0–15). Most of the sample declared nocturnal or daytime sleep problems (87.4%). Weak-to-moderate correlations were found between sleep disturbances and other NMS (range: 0.14–0.37). SCOPA-S subscales showed higher scores with the presence of most other NMS such as psychiatric complications and autonomic dysfunctions (p < 0.05). Regression models showed that fatigue, depression, urinary, cardiovascular, and thermoregulatory dysfunctions were significant determinants of SCOPA-NS score (variance: 23%); cognitive impairment, urinary, cardiovascular, and pupillomotor disorders influenced SCOPA-DS score (variance: 14%).ConclusionsInsomnia and daytime sleepiness are extremely prevalent in PD. Depression, fatigue, cognitive impairment, cardiovascular, urinary and thermoregulatory dysfunctions may contribute to insomnia/hypersomnia. This is the first clinical study to relate cardiovascular and thermoregulatory dysfunctions with sleep in PD.     

Bilateral pallidotomy in Parkinson's disease: a retrospective study.

We evaluated the effects of bilateral pallidotomy in patients with advanced Parkinson's disease. Thirteen patients with Parkinson's disease had a staged bilateral pallidotomy if they had severe response fluctuations, dyskinesias, painful dystonia, or bradykinesia despite optimum pharmacological treatment. Assessment scales were the Unified Parkinson's Disease Rating scale (UPDRS), the Schwab and England scale, and a questionnaire on the effects of disability in activities of daily living and adverse effects. Postoperative magnetic resonance imaging was evaluated for lesion location and extension. The median off-phase UPDRS motor score was reduced from 43.5 to 29 after the first pallidotomy, and it was further reduced to 23.5 after the second pallidotomy (n = 8). The UPDRS activities of daily living off-phase score improved from 28.5 to 20.5 after the first pallidotomy and to 19 after the second pallidotomy (n = 6). The Schwab and England scale off-phase score showed an improvement after both procedures, first from 40 to 60, and thereafter to 90 (n = 8). On-phase dyskinesias were reduced substantially. Eight patients had adverse effects, of whom five had problems with speech. One patient became hemiplegic due to a delayed infarction. Ten patients experienced further benefit from the second procedure. Bilateral pallidotomy reduces dyskinesias. A second contralateral pallidotomy may reduce parkinsonism, although to a lesser degree compared with the first pallidotomy and with an increased risk for adverse effects.     

Smoking and age-at-onset of both motor and non-motor symptoms in Parkinson's disease

IntroductionSeveral evidence suggest that smoking may decrease the risk of Parkinson's disease and is associated with an older age-at-onset of motor signs. The relation between smoking and age-at-onset of non-motor symptoms has never been analyzed. Objective of the study is to evaluate whether smoking habit and pack-years of smoking are associated with a delay of age-at-onset of motor signs, and of some non-motor symptoms.MethodsThe study population consisted of 262 consecutive parkinsonian patients. Information on relevant demographic/clinical data focused on motor signs, REM sleep behavior disorder, constipation, depression, and hyposmia. Patients were stratified according to smoking habit (ever-versus never-smoker) and number of pack-years of smoking was computed. Repeatability of data on age-at-onset was checked 6 months after the initial interview in a randomly recruited subsample.ResultsSmoking habit and number of pack-years smoked were associated with an older in age-at-onset of motor signs, REM sleep behavior disorder and depression. By contrast, smoking did not affect age-at-onset of hyposmia and constipation.Conclusioninformation from this study confirms that smoking may be associated with an older age-at-onset of motor signs, and that a similar effect can be observed on some non-motor symptoms like REM sleep behavior and depression.     

Gender differences in non-motor symptoms in early Parkinson's disease: A 2-years follow-up study on previously untreated patients

BackgroundWe recently showed specific sex-related patterns of non motor symptoms (NMS) in early, drug-naïve PD patients. However, to date studies investigating gender-related effects of dopaminergic treatment on NMS in early PD are lacking.MethodsIn the present study, we first report a prospective assessment of gender-related differences in the spectrum of NMS before (baseline) and after starting dopaminergic therapy (2-year follow-up) in a large cohort of newly diagnosed PD patients. Differences in NMS frequency between baseline and follow-up were evaluated by McNemar test. Spearman's rank test was employed to explore interactions between NMS and drug treatment.ResultsOne-hundred and thirty four PD patients (86M and 48W) were included in the present study. At 2-year follow-up, Sadness/blues presented a significant percentage reduction as compared to baseline in both sexes, while Urgency, Daytime sleepiness, Weight change and Sex drive presented a significant percentage increase only in men. At follow up men complained of a greater number of NMS as compared to women. Occurrence of Weight change was related to therapy in both sexes. Male gender was found to be a risk factor for developing Dribbling and Nocturia, irrespective of therapy and clinical features.ConclusionsIn conclusion, our study showed that mood symptoms improved after the introduction of therapy in both sexes, while men appeared to be more prone to develop some NMS possibly linked to dopaminergic treatment.     

Effects of long-term treatment with rotigotine transdermal system on dyskinesia in patients with early-stage Parkinson's disease

PurposeIn two 6-month, double-blind, placebo-controlled studies, rotigotine transdermal system was well-tolerated and efficacious monotherapy in early-stage PD. This post hoc analysis of the long-term open-label extensions (NCT00594165; NCT00599196) of these studies assessed incidence and severity of dyskinesia in participants treated with rotigotine, with or without concomitant levodopa, for up to 6 years.MethodsOpen-label rotigotine was titrated to optimal dose (≤16 mg/24 h). Concomitant levodopa was permitted. Dyskinesia data, recorded using the Unified Parkinson's Disease Rating Scale Part IV, were pooled from the two open-label studies.ResultsOf 596 participants who received open-label rotigotine, 299 (50%) remained at trial closure; no patient discontinued due to dyskinesia. In the two studies, median exposure to rotigotine was 1910 days (∼5 years, 3 months), and 1564.5 days (∼4 years, 3 months). During up to 6 years of open-label rotigotine, 423/596 (71%) received levodopa. Dyskinesias were reported in 115/596 (19%) participants, 90/115 (78%) of who developed dyskinesia after levodopa was added; 25 reported dyskinesia in the absence of levodopa (includes patients who never received open-label levodopa, and those who reported dyskinesia before starting concomitant levodopa). Dyskinesia severity data were available for 107 of the 115 participants. In 56/107 (52%) participants, dyskinesia was considered ‘not disabling’ for all occurrences; the worst-case severity was ‘mildly disabling’ for 33/107 (31%), and ‘moderately’ or ‘severely disabling’ for 18/107 (17%; 3% of total participants).ConclusionDuring treatment with rotigotine in patients with PD for up to 6 years the incidence of dyskinesia was low, and the dyskinesia was generally ‘not disabling’ or ‘mildly disabling’.     

Qigong exercise for the symptoms of Parkinson's disease: a randomized, controlled pilot study.

Irrespective of limited evidence, not only traditional physiotherapy, but also a wide array of complementary methods are applied by patients with Parkinson's disease (PD). We evaluated the immediate and sustained effects of Qigong on motor and nonmotor symptoms of PD, using an add-on design. Fifty-six patients with different levels of disease severity (mean age/standard deviation [SD], 63.8/7.5 years; disease duration 5.8/4.2 years; 43 men [76%]) were recruited from the outpatient movement disorder clinic of the Department of Neurology, University of Bonn. We compared the progression of motor symptoms assessed by Unified Parkinson's Disease Rating Scale motor part (UPDRS-III) in the Qigong treatment group (n = 32) and a control group receiving no additional intervention (n = 24). Qigong exercises were applied as 90-minute weekly group instructions for 2 months, followed by a 2 months pause and a second 2-month treatment period. Assessments were carried out at baseline, 3, 6, and 12 months. More patients improved in the Qigong group than in the control group at 3 and 6 months (P = 0.0080 at 3 months and P = 0.0503 at 6 months; Fisher's exact test). At 12 months, there was a sustained difference between groups only when changes in UPDRS-III were related to baseline. Depression scores decreased in both groups, whereas the incidence of several nonmotor symptoms decreased in the treatment group only.     

MRI biomarkers of motor and non-motor symptoms in Parkinson's disease

Parkinson's disease is a heterogeneous disorder with both motor and non-motor symptoms that contribute to functional impairment. To develop effective, disease modifying treatments for these symptoms, biomarkers are necessary to detect neuropathological changes early in the disease course and monitor changes over time. Advances in MRI scan sequences and analytical techniques present numerous promising metrics to detect changes within the nigrostriatal system, implicated in the cardinal motor symptoms of the disease, and detect broader dysfunction involved in the non-motor symptoms, such as cognitive impairment. There is emerging evidence that iron sensitive, neuromelanin sensitive, diffusion sensitive, and resting state functional magnetic imaging measures can capture changes within the nigrostriatal system. Iron, neuromelanin, and diffusion sensitive measures demonstrate high specificity and sensitivity in distinguishing Parkinson's disease relative to controls, with inconsistent results differentiating Parkinson's disease relative to atypical parkinsonian disorders. They may also serve as useful monitoring biomarkers, with each possibly detecting different aspects of the disease course (early nigrosome changes versus broader substantia nigra changes). Investigations of non-motor symptoms, such as cognitive impairment, require careful consideration of the nature of cognitive deficits to characterize regional and network specific impairment. While the early, executive dysfunction observed is consistent with nigrostriatal degeneration, the memory and visuospatial impairments, the harbingers of a dementia process reflect dopaminergic independent dysfunction involving broader regions of the brain.