Expanded and independent validation of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS).

PubMed

Martinez-Martin, Pablo; Rodriguez-Blazquez, Carmen; Alvarez-Sanchez, Mario; Arakaki, Tomoko; Bergareche-Yarza, Alberto; Chade, Anabel; Garretto, Nelida; Gershanik, Oscar; Kurtis, Monica M; Martinez-Castrillo, Juan Carlos; Mendoza-Rodriguez, Amelia; Moore, Henry P; Rodriguez-Violante, Mayela; Singer, Carlos; Tilley, Barbara C; Huang, Jing; Stebbins, Glenn T; Goetz, Christopher G

2013-01-01

The Movement Disorder Society-UPDRS (MDS-UPDRS) was published in 2008, showing satisfactory clinimetric results and has been proposed as the official benchmark scale for Parkinson's disease. The present study, based on the official MDS-UPDRS Spanish version, performed the first independent testing of the scale and adds information on its clinimetric properties. The cross-culturally adapted MDS-UPDRS Spanish version showed a comparative fit index ≥ 0.90 for each part (I-IV) relative to the English-language version and was accepted as the Official MDS-UPDRS Spanish version. Data from this scale, applied with other assessments to Spanish-speaking Parkinson's disease patients in five countries, were analyzed for an independent and complementary clinimetric evaluation. In total, 435 patients were included. Missing data were negligible and moderate floor effect (30 %) was found for Part IV. Cronbach's α index ranged between 0.79 and 0.93 and only five items did not reach the 0.30 threshold value of item-total correlation. Test-retest reliability was adequate with only two sub-scores of the item 3.17, Rest tremor amplitude, reaching κ values lower than 0.60. The intraclass correlation coefficient was higher than 0.85 for the total score of each part. Correlation of the MDS-UPDRS parts with other measures for related constructs was high (≥ 0.60) and the standard error of measurement lower than one-third baseline standard deviation for all subscales. Results confirm those of the original study and add information on scale reliability, construct validity, and precision. The MDS-UPDRS Spanish version shows satisfactory clinimetric characteristics.

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

PubMed

Attia; Ahmed, Hussien; Gadelkarim, Mohamed; Morsi, Mahmoud; Awad, Kamal; Elnenny, Mohamed; Ghanem, Esraa; El-Jaafary, Shaimaa; Negida, Ahmed

2017-01-01

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

Dose-Response Analysis of the Effect of Carbidopa-Levodopa Extended-Release Capsules (IPX066) in Levodopa-Naive Patients With Parkinson Disease.

PubMed

Mao, Zhongping Lily; Modi, Nishit B

2016-08-01

Parkinson disease is an age-related disorder of the central nervous system principally due to loss of dopamine-producing cells in the midbrain. Levodopa, in combination with carbidopa, is widely regarded as an effective treatment for the symptoms of Parkinson disease. A dose-response relationship is established for carbidopa-levodopa extended-release capsules (IPX066) in levodopa-naive Parkinson disease patients using a disease progression model. Unified Parkinson Disease Rating Scale (UPDRS) part II plus part III scores from 171 North American patients treated with placebo or IPX066 for approximately 30 weeks from a double-blind, parallel-group, dose-ranging study were used to develop the pharmacodynamic model. The model comprised 3 components: a linear function describing disease progression, a component describing placebo (or nonlevodopa) effects, and a component to describe the effect of levodopa. Natural disease progression in early Parkinson disease as measured by UPDRS was 11.6 units/year and faster in patients with more severe disease (Hoehn-Yahr stage 3). Maximum placebo/nonlevodopa response was 23.0% of baseline UPDRS. Maximum levodopa effect from IPX066 was 76.7% of baseline UPDRS, and the ED50 was 450 mg levodopa. Equilibration half-life for the effect compartment was 62.8 days. Increasing age increased and being female decreased equilibration half-life. The quantitative model allowed description of the entire time course of response to clinical trial intervention. © 2016, The Authors. The Journal of Clinical Pharmacology Published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

Measuring Disease Progression in Early Parkinson Disease: the National Institutes of Health Exploratory Trials in Parkinson Disease (NET-PD) Experience

PubMed Central

Parashos, Sotirios A.; Luo, Sheng; Biglan, Kevin M.; -Wollner, Ivan Bodis; He, Bo; Liang, Grace S.; Ross, G. Webster; Tilley, Barbara C.; Shulman, Lisa M.

2014-01-01

Importance Optimizing assessments of rate of progression in Parkinson Disease (PD) is important in designing clinical trials, especially of potential disease-modifying agents. Objective To examine the value of measures of impairment, disability, and quality of life in assessing progression in early Parkinson disease. Design, Setting, and Participants Inception cohort analysis of data from 413 early, untreated PD patients, who were enrolled in two multicenter, randomized, double-blind clinical trials. Intervention Participants were randomized into five treatments: 67 received creatine, 66 minocycline, 71 Coenzyme Q10, 71 GPI-1485, and 138 placebo. We assessed the association between the rates of change in measures of impairment, disability, and quality of life and time to initiation of symptomatic treatment. Main Outcome Measure Time between baseline assessment and need for the initiation of symptomatic pharmaceutical treatment for PD was the primary indicator of disease progression. Results After adjusting for baseline confounding variables Unified Parkinson Disease Rating Scale (UPDRS) II, UPDRS III, modified Rankin score (mRS), level of education, and treatment group, the rate of change of the following measurements was assessed: UPDRS II, UPDRS III, Schwab and England ADL (S&E), Total Functional Capacity (TFC), Parkinson’s Disease Quality of Life Questionnaire – 39 (PDQ39) ADL and Summary Index (SI), Short Form -12v2 Health Survey (SF12) Physical Summary (PS), and SF12 Mental Summary (MS). Variables reaching statistical threshold in univariate analysis were entered into a multivariable Cox proportional hazards model using time to symptomatic treatment as the dependent variable. More rapid worsening of UPDRS II (HR 1.15, 95% C.I. 1.08 – 1.22 for 1 scale unit change per 6 months), UPDRS III (HR 1.09; 95% C.I. 1.06 – 1.13 for 1 scale unit change per 6 months), and S&E (HR 1.29 95% C.I. 1.12 – 1.48 for 5 percentage point change per 6 months), was associated with earlier need for symptomatic therapy. Conclusions and Relevance In early PD, UPDRS II and III, and S&E can be used to measure disease progression, while the PDQ39 ADL, PDQ39 SI, TFC, SF12 PH, and SF12 MH are not sensitive to change. Trial Registration clinicaltrials.gov identifiers NCT00063193 and NCT00076492 PMID:24711047

Official Japanese Version of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale: validation against the original English version.

PubMed

Kashihara, Kenichi; Kondo, Tomoyoshi; Mizuno, Yoshikuni; Kikuchi, Seiji; Kuno, Sadako; Hasegawa, Kazuko; Hattori, Nobutaka; Mochizuki, Hideki; Mori, Hideo; Murata, Miho; Nomoto, Masahiro; Takahashi, Ryosuke; Takeda, Atsushi; Tsuboi, Yoshio; Ugawa, Yoshikazu; Yamanmoto, Mitsutoshi; Yokochi, Fusako; Yoshii, Fumihito; Stebbins, Glenn T; Tilley, Barbara C; Luo, Sheng; Wang, Lu; LaPelle, Nancy R; Goetz, Christopher G

2014-09-01

The Movement Disorder Society (MDS)-sponsored revision of the Unified Parkinson's Disease (PD) Rating Scale (UPDRS) (MDS-UPDRS) has been developed and is now available in English. Part of the overall program includes the establishment of official non-English translations of the MDS-UPDRS. We present the process for completing the official Japanese translation of the MDS-UPDRS with clinimetric testing results. In this trial, the MDS-UPDRS was translated into Japanese, underwent cognitive pre-testing, and the translation was modified after taking the results into account. The final translation was approved as Official Working Draft of the MDS-UPDRS Japanese version and tested in 365 native-Japanese-speaking patients with PD. Confirmatory analyses were used to determine whether the factor structure for the English-language MDS-UPDRS could be confirmed in data collected using the Official Working Draft of the Japanese translation. As a secondary analysis, we used exploratory factor analyses to examine the underlying factor structure without the constraint of a pre-specified factor organization. Confirmatory factor analysis revealed that Comparative Fit Index for all Parts of the MDS-UPDRS exceeded the minimal standard of 0.90 relative to the English version and therefore Japanese translation met the pre-specified criterion to be designated called an OFFICIAL MDS TRANSLATION. Secondary analyses revealed some differences between the English-language MDS-UPDRS and the Japanese translation, however, these differences were considered to be within an acceptable range. The Japanese version of the MDS-UPDRS met the criterion as an Official MDS Translation and is now available for use (www.movementdisorders.org).

Validation of the Italian version of the Movement Disorder Society--Unified Parkinson's Disease Rating Scale.

PubMed

Antonini, Angelo; Abbruzzese, Giovanni; Ferini-Strambi, Luigi; Tilley, Barbara; Huang, Jing; Stebbins, Glenn T; Goetz, Christopher G; Barone, Paolo; Bandettini di Poggio, Monica; Fabbrini, Giovanni; Di Stasio, Flavio; Tinazzi, Michele; Bovi, Tommaso; Ramat, Silvia; Meoni, Sara; Pezzoli, Gianni; Canesi, Margherita; Martinelli, Paolo; Maria Scaglione, Cesa Lorella; Rossi, Aroldo; Tambasco, Nicola; Santangelo, Gabriella; Picillo, Marina; Morgante, Letterio; Morgante, Francesca; Quatrale, Rocco; Sensi, MariaChiara; Pilleri, Manuela; Biundo, Roberta; Nordera, Giampietro; Caria, Antonella; Pacchetti, Claudio; Zangaglia, Roberta; Lopiano, Leonardo; Zibetti, Maurizio; Zappia, Mario; Nicoletti, Alessandra; Quattrone, Aldo; Salsone, Maria; Cossu, Gianni; Murgia, Daniela; Albanese, Alberto; Del Sorbo, Francesca

2013-05-01

The Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) has been available in English since 2008. As part of this process, the MDS-UPDRS organizing team developed guidelines for development of official non-English translations. We present here the formal process for completing officially approved non-English versions of the MDS-UPDRS and specifically focus on the first of these versions in Italian. The MDS-UPDRS was translated into Italian and tested in 377 native-Italian speaking PD patients. Confirmatory and exploratory factor analyses determined whether the factor structure for the English-language MDS-UPDRS could be confirmed in data collected using the Italian translation. To be designated an 'Official MDS translation,' the Comparative Fit Index (CFI) had to be ≥0.90 relative to the English-language version. For all four parts of the Italian MDS-UPDRS, the CFI, in comparison with the English-language data, was ≥0.94. Exploratory factor analyses revealed some differences between the two datasets, however these differences were considered to be within an acceptable range. The Italian version of the MDS-UPDRS reaches the criterion to be designated as an Official Translation and is now available for use. This protocol will serve as outline for further validation of this in multiple languages.

Safety and Efficacy of Rotigotine for Treating Parkinson's Disease: A Meta-Analysis of Randomised Controlled Trials.

PubMed

Chen, Fei; Jin, Lingjing; Nie, Zhiyu

2017-01-01

We aimed to comprehensively analyse the safety and efficiency of rotigotine for treating Parkinson's disease (PD). We conducted systematic literature searches of Cochrane library, PubMed and Embase databases up to April 2016, with 'Rotigotine', 'Parkinson Disease ' and 'Parkinson's disease' as key searching terms. Outcomes, including Unified Parkinson's Disease Rating Scale (UPDRS) Part III and Part II scores, 'off' time, adverse events (AEs), serious AEs and discontinuation because of AEs, were compared between rotigotine and placebo groups under a fixed or random effect model. For dichotomous and continuous data, risk ratio (RR) and weighted mean difference with their corresponding 95% confidence intervals (95% CIs) were taken as the effect sizes to calculate merged results. Twelve eligible studies were included. For patients with early or advanced PD, rotigotine could significantly improve UPDRS Part III and Part II scores (p < 0.001) and it had significantly higher incidence of AEs than the placebo (p < 0.001). Regarding discontinuation because of AEs, rotigotine showed a significant advantage over placebo in patients with early PD, whereas the overall result demonstrated no statistically significant difference between the groups. Rotigotine can improve daily living and motor ability of patients with PD, although it has higher incidence of AEs. Rotigotine might be more appropriate for patients with advanced PD than for those with early PD. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Validation of the Hebrew version of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale.

PubMed

Zitser, Jennifer; Peretz, Chava; Ber David, Aya; Shabtai, Herzl; Ezra, Adi; Kestenbaum, Meir; Brozgol, Marina; Rosenberg, Alina; Herman, Talia; Balash, Yakov; Gadoth, Avi; Thaler, Avner; Stebbins, Glenn T; Goetz, Christopher G; Tilley, Barbara C; Luo, Sheng T; Liu, Yuanyuan; Giladi, Nir; Gurevich, Tanya

2017-12-01

The Movement Disorders Society (MDS) published the English new Unified Parkinson's Disease Rating Scale (MDS-UPDRS) as the official benchmark scale for Parkinson's disease (PD) in 2008. We aimed to validate the Hebrew version of the MDS-UPDRS, explore its dimensionality and compare it to the original English one. The MDS-UPDRS questionnaire was translated to Hebrew and was tested on 389 patients with PD, treated at the Movement Disorders Unit at Tel-Aviv Medical Center. The MDS-UPDRS is made up of four sections. The higher the score, the worst the clinical situation of the patient is. Confirmatory and explanatory factor analysis were applied to determine if the factor structure of the English version could be confirmed in the Hebrew version. The Hebrew version of the MDS-UPDRS showed satisfactory clinimetric properties. The internal consistency of the Hebrew-version was satisfactory, with Cronbach's alpha values 0.79, 0.90, 0.93, 0.80, for parts 1 to 4 respectively. In the confirmatory factor analysis, all four parts had high (greater than 0.90) comparative fit index (CFI) in comparison to the original English MDS-UPDRS with high factor structure (0.96, 0.99, 0.94, 1.00, respectively), thus confirming the pre-specified English factor structure. Explanatory factor analysis yielded that the Hebrew responses differed from the English one within an acceptable range: in isolated item differences in factor structure and in the findings of few items having cross loading on multiple factors. The Hebrew version of the MDS-UPDRS meets the requirements to be designated as the Official Hebrew Version of the MDS-UPDRS. Copyright © 2017 Elsevier Ltd. All rights reserved.

Orthostatic hypotension predicts motor decline in early Parkinson disease.

PubMed

Kotagal, Vikas; Lineback, Christina; Bohnen, Nicolaas I; Albin, Roger L

2016-11-01

Orthostatic hypotension is increasingly reported as a risk factor for development of late-stage disease features in Parkinson disease (PD). Less is known about its significance in individuals with early PD who are often targeted for neuroprotective trials. Using data from the CALM-PD trial (n = 275), we explored whether early orthostatic hypotension predicts a decline in the Unified Parkinson's Disease Rating Scale (UPDRS) II (activities of daily living) or UDPRS III (motor) score after 102 weeks. We also explored risk factors for worsening orthostatic hypotension over a nearly 2-year period. After controlling for age, disease duration, gender, study drug, change in mini-mental status exam score, levodopa equivalent dose, and baseline UPDRS II or III score respectively, the degree of orthostatic hypotension at enrollment associated with a worsening in UPDRS motor score (t = 2.40, p = 0.017) at week 102 but not with UPDRS ADL score (t = 0.83, p = 0.409). Worsening in orthostatic hypotension during the study associated with longer disease duration (t = 2.37, p = 0.019) and lower body mass index (BMI) (t = -2.96, p = 0.003). Baseline orthostatic hypotension is a predictor of UPDRS motor decline in individuals with early PD and should be accounted for in clinical trial design. Low BMI may predict orthostatic hypotension in PD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Traditional chinese medicine improves activities of daily living in Parkinson's disease.

PubMed

Pan, Weidong; Kwak, Shin; Liu, Yun; Sun, Yan; Fang, Zhenglong; Qin, Baofeng; Yamamoto, Yoshiharu

2011-01-01

We evaluated the effects of a traditional Chinese medicine (TCM), named Zeng-xiao An-shen Zhi-chan 2 (ZAZ2), on patients with Parkinson's disease (PD). Among 115 patients with idiopathic PD enrolled (mean age, 64.7 ± 10.2 years old), 110 patients (M = 65, F = 45; mean age, 64.9 ± 10.7 years old) completed the study. Patients took either ZAZ2 (n = 59) or placebo granule (n = 56) in a blind manner for 13 weeks while maintaining other anti-Parkinson medications unchanged. All participants wore a motion logger, and we analyzed the power-law temporal autocorrelation of the motion logger records taken on 3 occasions (before, one week, and 13 weeks after the drug administration). Drug efficacy was evaluated with the conventional Unified Parkinson Disease Rating Scale (UPDRS), as well as the power-law exponent α, which corresponds to the level of physical activity of the patients. ZAZ2 but not placebo granule improved the awake-sleep rhythm, the UPDRS Part II, Part II + III, and Part IV scores, and the α values. The results indicate that ZAZ2 improved activities of daily living (ADL) of parkinsonism and, thus, is a potentially suitable drug for long-term use.

Impact of 6-month earlier versus postponed initiation of rotigotine on long-term outcome: post hoc analysis of patients with early Parkinson's disease with mild symptom severity.

PubMed

Timmermann, Lars; Asgharnejad, Mahnaz; Boroojerdi, Babak; Dohin, Elisabeth; Woltering, Franz; Elmer, Lawrence W

2015-01-01

Investigate impact of 6-month earlier versus postponed initiation of rotigotine in patients with early Parkinson's disease (PD) with mild symptom severity. Long-term benefit of rotigotine in early-PD has been demonstrated: SP702 (NCT00594165) and SP716 (NCT00599196) were long-term, open-label extensions of double-blind, placebo-controlled studies of 6-month maintenance; rotigotine was well tolerated for up to 6 years, and demonstrated efficacy (Unified Parkinson's Disease Rating Scale [UPDRS] II + III below baseline) for ∼ 2 years (SP702) and ∼ 4 years (SP716). Post hoc analysis of patients at Hoehn and Yahr 1-2; groups defined by treatment received in 6-month double-blind studies: 'Rotigotine-Rotigotine' received rotigotine (n = 221), 'Placebo-Rotigotine' received placebo (n = 125). At the start of open-label rotigotine maintenance, UPDRS II + III mean ± SD change from double-blind baseline was: -8.5 ± 10.6 'Rotigotine-Rotigotine', -7.7 ± 9.0 'Placebo-Rotigotine.' After this initial improvement scores gradually increased: It took ∼ 45 months for mean scores to cross baseline in 'Rotigotine-Rotigotine', and ∼ 21 months in 'Placebo-Rotigotine.' At the time mean UPDRS II + III had crossed baseline in 'Placebo-Rotigotine' (open-label week 84; ∼ 21 months), treatment difference (LS-mean) to 'Rotigotine-Rotigotine' change from baseline was -3.89 (95% CI -6.94, -0.84); p = 0.013. In this post hoc analysis, 6-month earlier initiation of rotigotine resulted in slower return to baseline mean UPDRS II + III; initiation of rotigotine in patients with minimal/no functional disability or impairment may lead to an extended benefit.

Validation of the korean-version of the nonmotor symptoms scale for Parkinson's disease.

PubMed

Koh, Seong-Beom; Kim, Jae Woo; Ma, Hyeo-Il; Ahn, Tae-Beom; Cho, Jin Whan; Lee, Phil Hyu; Chung, Sun Ju; Kim, Joong-Seok; Kwon, Do Young; Baik, Jong Sam

2012-12-01

Non-motor symptoms are common in Parkinson's disease (PD), and are the primary cause of disability in many PD patients. Our aim in this study was to translate the origin non-motor symptoms scale for PD (NMSS), which was written in English, into Korean (K-NMSS), and to evaluate its reliability and validity for use with Korean-speaking patients with PD. In total, 102 patients with PD from 9 movement disorders sections of university teaching hospitals in Korea were enrolled in this study. They were assessed using the K-NMSS, the Unified Parkinson's Disease Rating Scale (UPDRS), the Korean version of the Mini-Mental Status Examination (K-MMSE), the Korean version of the Montgomery-Asberg Depression Rating Scale (K-MADS), the Epworth Sleepiness Scale (ESS), and Parkinson's Disease Questionnaire 39 (PDQ39). Test-retest reliability was assessed over a time interval of 10-14 days in all but one patient. The K-NMSS was administered to 102 patients with PD. The internal consistency and reliability of this tool was 0.742 (mean Cronbach's α-coefficient). The test-retest correlation reliability was 0.941 (Guttman split-half coefficient). There was a moderate correlation between the total K-NMSS score and the scores for UPDRS part I [Spearman's rank correlation coefficient, (rS)=0.521, p<0.001] and UPDRS part II (rS=0.464, p=0.001), but there was only a weak correlation between the total K-NMSS score and the UPDRS part III score (rS=0.288, p=0.003). The total K-NMSS score was significantly correlated with the K-MADS (rS=0.594, p<0.001), K-MMSE (rS=-0.291, p=0.003), and ESS (rS=0.348, p<0.001). The total K-NMSS score was also significantly and positively correlated with the PDQ39 score (rS=0.814, p<0.001). The K-NMSS exhibited good reliability and validity for the assessment of non-motor symptoms in Korean PD patients.

Validation of the Korean-Version of the Nonmotor Symptoms Scale for Parkinson's Disease

PubMed Central

Koh, Seong-Beom; Kim, Jae Woo; Ma, Hyeo-Il; Ahn, Tae-Beom; Cho, Jin Whan; Lee, Phil Hyu; Chung, Sun Ju; Kim, Joong-Seok; Kwon, Do Young

2012-01-01

Background and Purpose Non-motor symptoms are common in Parkinson's disease (PD), and are the primary cause of disability in many PD patients. Our aim in this study was to translate the origin non-motor symptoms scale for PD (NMSS), which was written in English, into Korean (K-NMSS), and to evaluate its reliability and validity for use with Korean-speaking patients with PD. Methods In total, 102 patients with PD from 9 movement disorders sections of university teaching hospitals in Korea were enrolled in this study. They were assessed using the K-NMSS, the Unified Parkinson's Disease Rating Scale (UPDRS), the Korean version of the Mini-Mental Status Examination (K-MMSE), the Korean version of the Montgomery-Asberg Depression Rating Scale (K-MADS), the Epworth Sleepiness Scale (ESS), and Parkinson's Disease Questionnaire 39 (PDQ39). Test-retest reliability was assessed over a time interval of 10-14 days in all but one patient. Results The K-NMSS was administered to 102 patients with PD. The internal consistency and reliability of this tool was 0.742 (mean Cronbach's α-coefficient). The test-retest correlation reliability was 0.941 (Guttman split-half coefficient). There was a moderate correlation between the total K-NMSS score and the scores for UPDRS part I [Spearman's rank correlation coefficient, (rS)=0.521, p<0.001] and UPDRS part II (rS=0.464, p=0.001), but there was only a weak correlation between the total K-NMSS score and the UPDRS part III score (rS=0.288, p=0.003). The total K-NMSS score was significantly correlated with the K-MADS (rS=0.594, p<0.001), K-MMSE (rS=-0.291, p=0.003), and ESS (rS=0.348, p<0.001). The total K-NMSS score was also significantly and positively correlated with the PDQ39 score (rS=0.814, p<0.001). Conclusions The K-NMSS exhibited good reliability and validity for the assessment of non-motor symptoms in Korean PD patients. PMID:23323136

Transdermal Patch of Rotigotine Attenuates Freezing of Gait in Patients with Parkinson's Disease: An Open-Label Comparative Study of Three Non-Ergot Dopamine Receptor Agonists.

PubMed

Ikeda, Ken; Hirayama, Takehisa; Takazawa, Takanori; Kawabe, Kiyokazu; Iwasaki, Yasuo

Objective Parkinson's disease (PD) is characterized by the progressive degeneration of the nigrostriatal dopaminergic neurons. Rotigotine is a non-ergot dopamine receptor agonist (DA). Its transdermal patch maintains the effective concentrations for 24 hours. Freezing of gait (FOG) is a common and devastating symptom in PD patients. Little is known about therapeutic effects of rotigotine on FOG in PD patients. Herein we compared how three non-ergot DAs of rotigotine, pramipexole LA and ropinirole CR influence FOG, besides classical motor deficits in PD patients. Methods Rotigotine (maintenance doses of 9-27 mg/day) was administered in 51 patients, 36 patients received pramipexole LA (1.5-4.5 mg/day) and 35 patients received ropinirole CR (8-16 mg/day). The Unified PD Rating Scale (UPDRS) parts I-IV, FOG questionnaire (16 items) and wearing off time were examined from baseline to 7 months after DA administration. UPDRS parts I-IV were evaluated during on time and FOG was recorded during off time if patients experienced wearing off. Results A total of 111 patients completed the study. UPDRS parts II-III scores and wearing off time were significantly reduced after each DA treatment compared to baseline. FOG was found in 54 patients (49%). Most patients developed FOG during off time only. FOG scores were significantly decreased at 2 months after rotigotine treatment whereas pramipexole LA and ropinirole treatment did not alter FOG scores. Conclusion The present study indicates that transdermal patch of rotigotine attenuated the FOG off time. The similar binding affinities to dopamine receptors between rotigotine and dopamine, and 24 hours steady hemodynamics could contribute to the therapeutic mechanism of rotigotine on FOG in PD patients with wearing off.

Transdermal Patch of Rotigotine Attenuates Freezing of Gait in Patients with Parkinson's Disease: An Open-Label Comparative Study of Three Non-Ergot Dopamine Receptor Agonists

PubMed Central

Ikeda, Ken; Hirayama, Takehisa; Takazawa, Takanori; Kawabe, Kiyokazu; Iwasaki, Yasuo

2016-01-01

Objective Parkinson's disease (PD) is characterized by the progressive degeneration of the nigrostriatal dopaminergic neurons. Rotigotine is a non-ergot dopamine receptor agonist (DA). Its transdermal patch maintains the effective concentrations for 24 hours. Freezing of gait (FOG) is a common and devastating symptom in PD patients. Little is known about therapeutic effects of rotigotine on FOG in PD patients. Herein we compared how three non-ergot DAs of rotigotine, pramipexole LA and ropinirole CR influence FOG, besides classical motor deficits in PD patients. Methods Rotigotine (maintenance doses of 9-27 mg/day) was administered in 51 patients, 36 patients received pramipexole LA (1.5-4.5 mg/day) and 35 patients received ropinirole CR (8-16 mg/day). The Unified PD Rating Scale (UPDRS) parts I-IV, FOG questionnaire (16 items) and wearing off time were examined from baseline to 7 months after DA administration. UPDRS parts I-IV were evaluated during on time and FOG was recorded during off time if patients experienced wearing off. Results A total of 111 patients completed the study. UPDRS parts II-III scores and wearing off time were significantly reduced after each DA treatment compared to baseline. FOG was found in 54 patients (49%). Most patients developed FOG during off time only. FOG scores were significantly decreased at 2 months after rotigotine treatment whereas pramipexole LA and ropinirole treatment did not alter FOG scores. Conclusion The present study indicates that transdermal patch of rotigotine attenuated the FOG off time. The similar binding affinities to dopamine receptors between rotigotine and dopamine, and 24 hours steady hemodynamics could contribute to the therapeutic mechanism of rotigotine on FOG in PD patients with wearing off. PMID:27725534

Rotigotine transdermal patch in Chinese patients with early Parkinson's disease: A randomized, double-blind, placebo-controlled pivotal study.

PubMed

Zhang, Zhen-Xin; Shang, Hui-Fang; Hu, Xingyue; Chen, Shengdi; Zhao, Zhongxin; Du, Xinlu; Surmann, Erwin; Bauer, Lars; Asgharnejad, Mahnaz

2016-07-01

Two phase3 studies (SP512; SP513) involving mostly Caucasian patients showed that rotigotine (≤8 mg/24 h) was efficacious and welltolerated in early-stage Parkinson's disease (PD). We report results from a phase 3 study (SP0914/NCT01646268) investigating rotigotine in Chinese patients with early-stage PD. Patients were randomized 1:1 to rotigotine or placebo, titrated over 1-4 weeks, maintained at optimal/maximum dose (≤8 mg/24 h) for 24 weeks. Primary efficacy variable: change in Unified Parkinson's Disease Rating Scale (UPDRS) II + III total score from Baseline to End-of-Maintenance. Secondary variables: UPDRS II + III responders (≥20% decrease in UPDRS II + III) and changes in UPDRS II (activities of daily living [ADL]) and III (motor examination) subscores. Of 247 patients randomized, 113/124 (91.1%) rotigotine- and 107/123 (87.0%) placebo-treated patients completed the study. mean (SD) age: 59.4 (10.2) years; time since PD diagnosis: 1.01 (1.22) years, 60.7% male. Rotigotine significantly improved UPDRS II + III total score (change from Baseline LSmean [95%CI] treatment difference, -4.82 [-7.18 to -2.45]; P < 0.0001). UPDRS II + III responder rates were higher with rotigotine (42.3% vs 22.3%; P = 0.0006). UPDRS II and III subscores improved with rotigotine (both subscores: P < 0.0005 vs. placebo). Most frequent adverse events (AEs): nausea (8.9% rotigotine, 3.3% placebo), dizziness (8.1%, 5.7%), pruritus (8.1%, 4.1%), somnolence (8.1%, 3.3%), erythema (6.5%, 1.6%), and vomiting (5.6%, 1.6%). Thirteen (5.3%) patients discontinued due to AEs (6 rotigotine, 7 placebo). Rotigotine was efficacious in Chinese patients with early-stage PD, providing benefits to control of ADL and motor function. Rotigotine was generally welltolerated, with similar AEs to those observed in Caucasian patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

A systematic review and mixed treatment comparison of monotherapy in early Parkinson's disease: implications for Latin America.

PubMed

Márquez-Cruz, Maribel; Díaz-Martínez, Juan Pablo; Soto-Molina, Herman; De Saráchaga, Adib Jorge; Cervantes-Arriaga, Amin; Llorens-Arenas, Rodrigo; Rodríguez-Violante, Mayela

2016-01-01

Parkinson's disease (PD) is the second most common neurodegenerative disease. There are no clinical trials comparing all available pharmacological therapies for the treatment of early PD. The objective of this review is to indirectly analyze the efficacy of antiparkinson drugs currently available in Latin America. A systematic review was performed exploring only placebo-controlled randomized trials comparing antiparkinson monotherapy (levodopa, pramipexole, rasagiline, or selegiline) in patients with PD on Hoehn and Yahr stages I through III published from January 1994 to May 2014. The primary outcome was the mean change in the Unified PD Rating Scale (UPDRS) I, II and III. A mixed treatment comparison analysis (indirect comparisons) through a random-effects model was performed. Levodopa demonstrated the highest effects in terms of UPDRS score improvement both from baseline and when compared to other treatments. Levodopa showed a 60.1% probability of granting the greatest reduction in UPDRS I, II and III.

Does integrative medicine enhance balance in aging adults? Proof of concept for the benefit of electroacupuncture therapy in Parkinson's disease.

PubMed

Toosizadeh, Nima; Lei, Hong; Schwenk, Michael; Sherman, Scott J; Sternberg, Esther; Mohler, Jane; Najafi, Bijan

2015-01-01

Postural balance and potentially fall risk increases among older adults living with neurological diseases, especially Parkinson's disease (PD). Since conventional therapies such as levodopa or deep brain stimulation may fail to alleviate or may even worsen balance, interest is growing in evaluating alternative PD therapies. The purpose of the current study was to assess improvement in postural balance in PD patients following electroacupuncture (EA) as an alternative therapy. 15 aging adults (71.2 ± 6.3 years) with idiopathic PD and 44 healthy age-matched participants (74.6 ± 6.5 years) were recruited. The PD participants were randomly assigned (at a ratio of 2:1) to an intervention (n = 10) or to a control group (n = 5). The intervention group received a 30-min EA treatment on a weekly basis for 3 weeks, while the control group received a sham treatment. Outcomes were assessed at baseline and after the final therapy. Measurements included balance assessment, specifically the ratio of medial-lateral (ML) center-of-gravity (COG) sway to anterior-posterior (AP) sway (COGML/AP) and ankle/hip sway during eyes-open, eyes-closed, and eyes-open dual-task trials, the Unified Parkinson's Disease Rating Scale (UPDRS), as well as quality of life, concerns for fall, and pain questionnaires. No difference was observed for the assessed parameters between the intervention and the control group at baseline. After treatment, an improvement in balance performance was observed in the intervention group. Compared with the healthy population, PD patients prior to treatment had larger COGML/AP sway with more dependency on upper-body movements for maintaining balance. Following EA therapy, COGML/AP sway was reduced by 31% and ankle/hip sway increased by 46% in the different conditions (p = 0.02 for the dual-task condition). The clinical rating revealed an overall improvement (p < 0.01) in mentation, behavior, and mood (UPDRS part I, 49%), activities of daily living (UPDRS part II, 46%), and motor examination (UPDRS part III, 40%). There was a significant reduction (p < 0.02) in the specific items regarding UPDRS fall status (67%) and rigidity (48%). Changes were small and nonsignificant in the controls (p > 0.29). This pilot study demonstrates improvement in rigidity and balance following EA. These preliminary results suggest EA could be a promising alternative treatment for balance disturbance in PD. © 2014 S. Karger AG, Basel.

Caffeine as symptomatic treatment for Parkinson disease (Café-PD): A randomized trial.

PubMed

Postuma, Ronald B; Anang, Julius; Pelletier, Amelie; Joseph, Lawrence; Moscovich, Mariana; Grimes, David; Furtado, Sarah; Munhoz, Renato P; Appel-Cresswell, Silke; Moro, Adriana; Borys, Andrew; Hobson, Douglas; Lang, Anthony E

2017-10-24

To assess effects of caffeine on Parkinson disease (PD). In this multicenter parallel-group controlled trial, patients with PD with 1-8 years disease duration, Hoehn & Yahr stages I-III, on stable symptomatic therapy were randomized to caffeine 200 mg BID vs matching placebo capsules for 6-18 months. The primary research question was whether objective motor scores would differ at 6 months (Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale [MDS-UPDRS]-III, Class I evidence). Secondary outcomes included safety and tolerability, motor symptoms (MDS-UPDRS-II), motor fluctuations, sleep, nonmotor symptoms (MDS-UPDRS-I), cognition (Montreal Cognitive Assessment), and quality of life. Sixty patients received caffeine and 61 placebo. Caffeine was well-tolerated with similar prevalence of side effects as placebo. There was no improvement in motor parkinsonism (the primary outcome) with caffeine treatment compared to placebo (difference between groups -0.48 [95% confidence interval -3.21 to 2.25] points on MDS-UPDRS-III). Similarly, on secondary outcomes, there was no change in motor signs or motor symptoms (MDS-UPDRS-II) at any time point, and no difference on quality of life. There was a slight improvement in somnolence over the first 6 months, which attenuated over time. There was a slight increase in dyskinesia with caffeine (MDS-UPDRS-4.1+4.2 = 0.25 points higher), and caffeine was associated with worse cognitive testing scores (average Montreal Cognitive Assessment = 0.66 [0.01, 1.32] worse than placebo). Caffeine did not provide clinically important improvement of motor manifestations of PD (Class I evidence). Epidemiologic links between caffeine and lower PD risk do not appear to be explained by symptomatic effects. NCT01738178. This study provides Class I evidence that for patients with PD, caffeine does not significantly improve motor manifestations. © 2017 American Academy of Neurology.

Efficacy, safety, and tolerance of the non-ergoline dopamine agonist pramipexole in the treatment of advanced Parkinson's disease: a double blind, placebo controlled, randomised, multicentre study.

PubMed

Pinter, M M; Pogarell, O; Oertel, W H

1999-04-01

Pramipexole, a non-ergot dopamine D2/D3 receptor agonist, was investigated as an add on drug in advanced parkinsonian patients with motor fluctuations to assess efficacy, safety, and tolerance. Seventy eight patients of either sex with advanced Parkinson's disease and treatment complications such as motor fluctuations were enrolled into a double blind, placebo controlled, randomised, multicentre study (phase II) and assigned to add on treatment with pramipexole (n=34) versus placebo (n=44) to a previously stabilised antiparkinsonian medication (7 week dose titration interval, 4 week maintenance period). The primary end point of efficacy was the change from baseline in the total score of the unified Parkinson's disease rating scale (UPDRS) in the on "period" (2 hours after intake of study medication). Safety and tolerability were assessed on the basis of adverse events, vital signs, laboratory measurements, and ECG recordings. There was a significant improvement of the pramipexole group in UPDRS total scores, subscores part II, III (activities of daily living and motor examination), and IV (complications of therapy). Mean UPDRS total score decreased by 37.3% under pramipexole compared with 12.2% under placebo (p<0.001). Patients under pramipexole reported an overall reduction in "off" periods of 12%--resulting in 1.7 more hours "on" time a day--compared with an increase in "off" periods of 2% under placebo. There were no unexpected safety results. The adverse event profile disclosed a high tolerability. The most important adverse events under pramipexole were fatigue, dyskinesia, and vivid dreams. Pramipexole administration is an efficacious and well tolerated add on therapy in patients with advanced Parkinson's disease with an improvement in activities of daily living, motor function, and treatment associated complications.

Traditional Chinese Medicine Improves Activities of Daily Living in Parkinson's Disease

PubMed Central

Pan, Weidong; Kwak, Shin; Liu, Yun; Sun, Yan; Fang, Zhenglong; Qin, Baofeng; Yamamoto, Yoshiharu

2011-01-01

We evaluated the effects of a traditional Chinese medicine (TCM), named Zeng-xiao An-shen Zhi-chan 2 (ZAZ2), on patients with Parkinson's disease (PD). Among 115 patients with idiopathic PD enrolled (mean age, 64.7 ± 10.2 years old), 110 patients (M = 65, F = 45; mean age, 64.9 ± 10.7 years old) completed the study. Patients took either ZAZ2 (n = 59) or placebo granule (n = 56) in a blind manner for 13 weeks while maintaining other anti-Parkinson medications unchanged. All participants wore a motion logger, and we analyzed the power-law temporal autocorrelation of the motion logger records taken on 3 occasions (before, one week, and 13 weeks after the drug administration). Drug efficacy was evaluated with the conventional Unified Parkinson Disease Rating Scale (UPDRS), as well as the power-law exponent α, which corresponds to the level of physical activity of the patients. ZAZ2 but not placebo granule improved the awake-sleep rhythm, the UPDRS Part II, Part II + III, and Part IV scores, and the α values. The results indicate that ZAZ2 improved activities of daily living (ADL) of parkinsonism and, thus, is a potentially suitable drug for long-term use. PMID:21687764

Evaluation of rotigotine transdermal patch for the treatment of depressive symptoms in patients with Parkinson's disease.

PubMed

Chung, Sun Ju; Asgharnejad, Mahnaz; Bauer, Lars; Ramirez, Francisco; Jeon, Beomseok

2016-08-01

To evaluate the dopamine receptor agonist, rotigotine, for improving depressive symptoms in patients with Parkinson's disease (PD). Patients were randomized 1:1 to rotigotine or placebo, titrated for ≤7 weeks, and maintained at optimal/maximum dose for 8-weeks. Primary efficacy variable: 17- item Hamilton Depression Rating Scale (HAM-D 17) total score change from baseline to end-of-maintenance. Secondary variables: changes in Beck Depression Inventory-II, Unified Parkinson's Disease Rating Scale (UPDRS) II (activities of daily living [ADL]) and III (motor) subscores, UPDRS II+III total, patient-rated Apathy Scale (AS), and Snaith-Hamilton Pleasure Scale. Of 380 patients randomized, 149/184 (81.0%) rotigotine-treated and 164/196 (83.7%) placebo-treated patients completed the study. mean (±SD) age 65.2 (±8.5) years; time since PD-diagnosis 2.74 (±3.08) years; 42.6% male. The treatment difference (LS mean [95% CI]) in change from baseline HAM-D 17 was -1.12 (-2.56, 0.33; p = 0.1286). UPDRS II, III, II+III and AS scores improved numerically with rotigotine versus placebo. Common adverse events with higher incidence with rotigotine: nausea, application/instillation site reactions, vomiting, and pruritus. Forty-one (10.8%) patients discontinued owing to adverse events (25 rotigotine/16 placebo). No statistically significant improvement in depressive symptoms were observed with rotigotine versus placebo. ADL, motor function, and patient-rated apathy improved numerically. ClinicalTrials.gov: NCT01523301.

A comparison of sumanirole versus placebo or ropinirole for the treatment of patients with early Parkinson's disease.

PubMed

Singer, Carlos; Lamb, Janice; Ellis, Amanda; Layton, Gary

2007-03-15

To assess the safety and efficacy of sumanirole, a highly selective dopamine agonist, versus placebo and demonstrate its noninferiority to ropinirole, 614 patients with early Parkinson's disease (PD) were treated with sumanirole, 1 to 16 mg/day; ropinirole, 0.75 to 24 mg/day; or placebo. Primary end point in this flexible-dose, double-blind, double-dummy, parallel-group study of 40 weeks was the change in total sum of the United Parkinson's Disease Rating Scale (UPDRS) Parts II + III scores from baseline to end of maintenance. Approximately half the subjects in the sumanirole and placebo groups withdrew early from the study, most (51.8% and 68.5%, respectively) due to lack of efficacy. Of the ropinirole subjects who withdrew (50.5%), most discontinued because of adverse events. In sumanirole and ropinirole groups, mean changes from baseline of -2.48 and -5.20 in UPDRS II + III mean scores were significant versus 0.38 in the placebo group (P

Baseline prevalence and longitudinal evolution of non-motor symptoms in early Parkinson's disease: the PPMI cohort.

PubMed

Simuni, Tanya; Caspell-Garcia, Chelsea; Coffey, Christopher S; Weintraub, Daniel; Mollenhauer, Brit; Lasch, Shirley; Tanner, Caroline M; Jennings, Danna; Kieburtz, Karl; Chahine, Lana M; Marek, Kenneth

2018-01-01

To examine the baseline prevalence and longitudinal evolution in non-motor symptoms (NMS) in a prospective cohort of, at baseline, patients with de novo Parkinson's disease (PD) compared with healthy controls (HC). Parkinson's Progression Markers Initiative (PPMI) is a longitudinal, ongoing, controlled study of de novo PD participants and HC. NMS were rated using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I score and other validated NMS scales at baseline and after 2 years. Biological variables included cerebrospinal fluid (CSF) markers and dopamine transporter imaging. 423 PD subjects and 196 HC were enrolled and followed for 2 years. MDS-UPDRS Part I total mean (SD) scores increased from baseline 5.6 (4.1) to 7.7 (5.0) at year 2 in PD subjects (p<0.001) versus from 2.9 (3.0) to 3.2 (3.0) in HC (p=0.38), with a significant difference between the groups (p<0.001). In the multivariate analysis, higher baseline NMS score was associated with female sex (p=0.008), higher baseline MDS-UPDRS Part II scores (p<0.001) and more severe motor phenotype (p=0.007). Longitudinal increase in NMS severity was associated with the older age (0.008) and lower CSF Aβ1-42 (0.005) at baseline. There was no association with the dose or class of dopaminergic therapy. This study of NMS in early PD identified clinical and biological variables associated with both baseline burden and predictors of progression. The association of a greater longitudinal increase in NMS with lower baseline Aβ1-42 level is an important finding that will have to be replicated in other cohorts. ClinicalTrials.gov identifier: NCT01141023. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Only physical aspects of quality of life are significantly improved by bilateral subthalamic stimulation in Parkinson's disease.

PubMed

Drapier, Sophie; Raoul, Sylvie; Drapier, Dominique; Leray, Emmanuelle; Lallement, François; Rivier, Isabelle; Sauleau, Paul; Lajat, Youen; Edan, Gilles; Vérin, Marc

2005-05-01

The well known global improvement of quality of life (QoL) after bilateral high frequency chronic deep brain stimulation of the subthalamic nucleus (STN DBS) in Parkinson's disease (PD) is in contrast to behavioral disturbances as observed after surgery. Indeed the impact of DBS on physical versus mental aspects of QoL in PD remains unknown. To assess the influence of bilateral STN DBS on physical versus mental aspects of QoL in Parkinson's disease. The results of 27 patients for the Unified Parkinson's disease Rating Scale (UPDRS), Parkinson's Disease Questionnaire 39 (PDQ39) and Short Form 36 health survey questionnaire (SF36) were compared before surgery and after 12 months of bilateral STN DBS. Comparing off-dopa conditions before versus 12 months after surgery, both UPDRS part II and part III significantly improved: 32.6% and 52%, respectively. UPDRS part I scores did not change significantly at 12 months. As for PDQ39, the global score significantly improved after surgery (21.1 %) as did four subscores: mobility (25.6 %), activity of daily living (34.5 %), stigma (40.1 %) and bodily discomfort (30 %). Three PDQ39 subscores, however, showed no significant changes: emotional well-being (10.7 %), social support (3.2%) and cognition (8.5 %) and one item even worsened: communication (-7.7 %). In SF36, only physical items significantly improved. Using clinician's based rating scale, bilateral STN DBS showed significant improvement in PD patients at 12 month follow up. However, using patient's self-assessment scales, the clinical benefit of STN DBS was more subtle: physical items of QoL significantly improved, whereas mental items such as emotional well-being, social support, cognition and communication showed no improvement. Our results are suggestive of a dissociation of motor and non-motor symptoms control after bilateral STN DBS in PD patients.

Disability in Activities of Daily Living and Severity of Dyskinesias Determine the Handicap of Parkinson's Disease Patients in Advanced Stage Selected to DBS.

PubMed

Coelho, Miguel; Abreu, Daisy; Correia-Guedes, Leonor; Lobo, Patricia Pita; Fabbri, Margherita; Godinho, Catarina; Domingos, Josefa; Albuquerque, Luisa; Freitas, Vanda; Pereira, João Miguel; Cattoni, Begona; Carvalho, Herculano; Reimão, Sofia; Rosa, Mário M; Ferreira, António Gonalves; Ferreira, Joaquim J

2017-01-01

There is scarce data on the level of handicap in Parkinson's disease (PD) and none in advanced stage PD. To assess the handicap in advanced stage PD patients with disabling levodopa-induced motor complications selected to deep brain stimulation (DBS). Data was prospectively recorded during routine evaluation for DBS. Handicap was measured using London Handicap Scale (LHS) (0 = maximal handicap; 1 = no handicap). Disease severity was evaluated using the Hoehn & Yahr scale and the UPDRS/MDS-UPDRS, during off and on after a supra-maximal dose of levodopa. Schwab and England Scale (S&E) was scored in off and on. Dyskinesias were scored using the modified Abnormal Involuntary Movement Scale (mAIMS). Results concern cross-sectional assessment before DBS. 100 PD patients (mean age 61 (±7.6); mean disease duration 12.20 (±4.6) years) were included. Median score of motor MDS-UPDRS was 54 in off and 25 in on. Mean total LHS score was 0.56 (±0.14). Patients were handicapped in several domains with a wide range of severity. Physical Independence and Social Integration were the most affected domains. Determinants of total LHS score were MDS-UPDRS part II off (β= -0.271; p = 0.020), S&E on (β= 0.264; p = 0.005) and off (β= 0.226; p = 0.020), and mAIMS on (β= -0.183; p = 0.042) scores (R2  = 29.6%). We were able to use handicap to measure overall health condition in advanced stage PD. Patients were moderately to highly handicapped and this was strongly determined by disability in ADL and dyskinesias. Change in handicap may be a good patient-centred outcome to assess efficiency of DBS.

Influence of physiotherapy on severity of motor symptoms and quality of life in patients with Parkinson disease.

PubMed

Cholewa, J; Boczarska-Jedynak, M; Opala, G

2013-01-01

Parkinson disease (PD) is one of the most frequent diseases of the central nervous system. Rehabilitation is one of the factors which may help the patients to maintain higher physical activity in everyday life. The aim of this work was to evaluate the influence of movement rehabilitation on severity of motor symptoms in PD patients. The study included 70 patients suffering from PD according to the Hoehn and Yahr scale. Patients' clinical status was assessed with Unified Parkinson's Disease Rating Scale (UPDRS) parts I-III. Additionally, activity of daily living was evaluated with the Schwab and England scale. The quality of life was evaluated by the Parkinson's Disease Questionnaire (PDQ-39). The examinations were conducted before and after the twelve weeks of the experiment. Patients included in the intervention group (n = 40) took part in 60-minute rehabilitation exercises twice a week, which were aimed at increasing movement ranges, balance improvement, movement agility and walking. The main emphasis was placed on the ability to cope with daily activities. A significant difference in scores of given scales before and after the 12-week period was observed in the intervention group: UPDRS part I score decreased by 17.31%, part II decreased by 22.2%, part III decreased by 18.96%, and PDQ-39 score decreased by 17.12%. Mean score of the Schwab and England scale increased by 9.69%, indicating an improved quality of life. The applied rehabilitation programme decreased the severity of motor symptoms in patients with PD.

Land Plus Aquatic Therapy Versus Land-Based Rehabilitation Alone for the Treatment of Balance Dysfunction in Parkinson Disease: A Randomized Controlled Study With 6-Month Follow-Up.

PubMed

Palamara, Grazia; Gotti, Francesco; Maestri, Roberto; Bera, Rossana; Gargantini, Roberto; Bossio, Fabiola; Zivi, Ilaria; Volpe, Daniele; Ferrazzoli, Davide; Frazzitta, Giuseppe

2017-06-01

To assess whether a specific land-based physical intervention with the inclusion of aquatic therapy is more effective than land-based rehabilitation alone for the treatment of balance dysfunction in patients with Parkinson disease (PD), immediately after therapy and at 6 months' follow-up. Randomized controlled study with 6-month follow-up. A PD and brain injury rehabilitation department in a general hospital. Patients (N=34) with moderate-stage PD. Seventeen patients underwent a land-based rehabilitation protocol called multidisciplinary intensive rehabilitation treatment (MIRT), and 17 underwent MIRT plus aquatic therapy (MIRT-AT). The primary outcome measure was the Berg Balance Scale (BBS); secondary outcome measures were the Unified Parkinson Disease Rating Scale parts II and III (UPDRS II/III) and the Timed Up and Go (TUG) test. These measures were assessed in both groups at admission, at discharge, and after 6 months. BBS improved after treatment in both groups. Even though no statistically significant difference between groups was observed at each observation time, BBS scores at follow-up were significantly higher than at baseline in MIRT-AT patients. Both groups also showed an improvement in UPDRS II/III and TUG at the end of treatment compared with baseline, but these findings were lost at the 6-month follow-up. Aquatic therapy added to land-based rehabilitation could provide a contribution to the treatment of balance dysfunction in patients with moderate-stage PD. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Does Integrative Medicine Enhance Balance in Aging Adults? – Proof of Concept for Benefit of Electro-acupuncture Therapy in Parkinson's Disease

PubMed Central

Toosizadeh, Nima; Lei, Hong; Schwenk, Michael; Sherman, Scott J.; Esternberg, Esther; Mohler, Jane; Najafi, Bijan

2014-01-01

Background Postural balance and potentially fall risk increases among older adults living with neurological diseases, especially Parkinson's disease (PD). Since conventional therapies, such as levodopa or deep brain stimulation may fail to alleviate or may even worsen balance, interest is growing in evaluating alternative PD therapies. Objective The purpose of the current study was to assess improvement in postural balance in PD patients following electro-acupuncture (EA), as an alternative therapy. Methods Fifteen aging adults (70.2 ± 7.3 years) with idiopathic PD and 44 healthy age- matched participants (74.6 ± 6.5 years) were recruited. PD participants were randomly assigned (with a ratio of 2 to 1) to an intervention (n=10) or to a control group (n=5). The intervention group received a 30-minute EA treatment on a weekly basis for three weeks, while the control group received a sham treatment. Outcomes were assessed at baseline and after the final therapy. Measurements included balance assessment, specifically ratio of medial-lateral (ML) center of gravity (COG) sway to anterior-posterior (AP) sway (COGML/AP) and ankle-to-hip sway during eyes-open, eyes-closed, and eyes-open dual-tasks trials, Unified Parkinson's Disease Rating Scale (UPDRS), and quality of life, concerns for fall, and pain questionnaires. Results No difference was observed for assessed parameters between intervention and control groups in baseline. After treatment, improvement in balance performance was observed in the intervention group. Compared with a healthy population, PD patients prior to treatment had larger COGML/AP sway with more dependency on upper-body movements for maintaining balance. Following EA therapy, COGML/AP sway reduced by 31% and Ankle/Hip sway increased by 46% among different conditions (p = 0.02 for dual-task condition). The clinical rating revealed an overall improvement (p < 0.01) in the activity of daily living (UPDRS part II, 46%) and motor examination (UPDRS part III, 40%). There was significant reduction (p < 0.02) in the specific items regarding UPDRS fall status (67%), and rigidity (48%). Changes were small and non-significant in the controls (p > 0.29). Conclusions This pilot study demonstrated improvement in rigidity and balance following EA. These preliminary results suggest EA could be a promising alternative treatment for balance disturbance in PD. PMID:25341431

[123I]beta-CIT SPECT visualizes dopamine transporter loss in de novo parkinsonian patients.

PubMed

Müller, T; Farahati, J; Kuhn, W; Eising, E G; Przuntek, H; Reiners, C; Coenen, H H

1998-01-01

Parkinson's disease (PD) is characterized by degeneration of dopaminergic neurons in the basal ganglia, which may be visualized by single photon emission computed tomography (SPECT) in combination with the cocaine analog methyl-3-beta-(4-beta[123I]iodophenyl)tropane-2beta-carboxylate ([123I]beta-CIT). The aim of our study was to correlate findings of SPECT with clinical data of 34 previously untreated, idiopathic parkinsonian patients [age: 59.58+/-10.03 (mean+/-SD) years; Hoehn and Yahr Scale (HYS) mean range: 1.97+/-0.83, ranges I-III; Unified PD Rating Scale 3.0 (UPDRS, 30.64+/-18.68) and 15 healthy controls (age 47.93+/-10.47 years). SPECT scans were performed with a single-head gamma-camera 24 h after intravenous injection of [123I]beta-CIT. Comparison of the striatum/cerebellum (S/C) ratio of [123I]beta-CIT uptake of controls and parkinsonian subjects, subdivided according to their HYS range, was significant. No influence of age or sex was observed. Significant correlations were found between scores of the HYS, UPDRS parts I-III, part II, part III, and the S/C ratio of [123I]-CIT uptake. Moreover, SPECT with the radiotracer [123I]beta-CIT revealed side-to-side differences in parkinsonian patients and significant associations to contralateral clinical extrapyramidal symptomatology. Our data show that SPECT with [123I]beta-CIT is a valuable tool for estimating disease severity in PD.

Efficacy of antidepressive medication for depression in Parkinson disease: a network meta-analysis

PubMed Central

Zhuo, Chuanjun; Xue, Rong; Luo, Lanlan; Ji, Feng; Tian, Hongjun; Qu, Hongru; Lin, Xiaodong; Jiang, Ronghuan; Tao, Ran

2017-01-01

Abstract Background: Parkinson disease (PD) was considered as the 2nd most prevalent neurodegenerative disorder after Alzheimer disease, while depression is a prevailing nonmotor symptom of PD. Typically used antidepression medication includes tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRI), serotonin and norepinephrine reuptake inhibitors (SNRI), monoamine-oxidase inhibitors (MAOI), and dopamine agonists (DA). Our study aimed at evaluating the efficacy of antidepressive medications for depression of PD. Methods: Web of Science, PubMed, Embase, and the Cochrane library were searched for related articles. Traditional meta-analysis and network meta-analysis (NMA) were performed with outcomes including depression score, UPDRS-II, UPDRS-III, and adverse effects. Surface under the cumulative ranking curve (SUCRA) was also performed to illustrate the rank probabilities of different medications on various outcomes. The consistency of direct and indirect evidence was also assessed by node-splitting method. Results: Results of traditional pairwise meta-analysis were performed. Concerning depression score, significant improvement was observed in AD, MAOI, SSRI, and SNRI compared with placebo. NMA was performed and more information could be obtained. DA was illustrated to be effective over placebo concerning UPDRS-III, MAOI, and SNRI. DA demonstrated a better prognosis in UPDRS-II scores compared with placebo and MAOI. However, DA and SSRI demonstrated a significant increase in adverse effects compared with placebo. The SUCRA value was calculated to evaluate the ranking probabilities of all medications on investigated outcomes, and the consistency between direct and indirect evidences was assessed by node-splitting method. Conclusion: SSRI had a satisfying efficacy for the depression of PD patients and could improve activities of daily living and motor function of patient but the adverse effects are unneglectable. SNRI are the safest medication with high efficacy for depression as well while other outcomes are relatively poor. PMID:28562526

Adherence therapy improves medication adherence and quality of life in people with Parkinson's disease: a randomised controlled trial.

PubMed

Daley, D J; Deane, K H O; Gray, R J; Clark, A B; Pfeil, M; Sabanathan, K; Worth, P F; Myint, P K

2014-08-01

Many factors are associated with medication non-adherence in Parkinson's disease (PD), including complex treatment regimens, mood disorders and impaired cognition. However, interventions to improve adherence which acknowledge such factors are lacking. A phase II randomised controlled trial was conducted investigating whether Adherence Therapy (AT) improves medication adherence and quality of life (QoL) compared with routine care (RC) in PD. Eligible PD patients and their spouse/carers were randomised to intervention (RC plus AT) or control (RC alone). Primary outcomes were change in adherence (Morisky Medication Adherence Scale) and QoL (Parkinson's Disease Questionnaire-39) from baseline to week-12 follow up. Secondary outcomes were MDS-UPDRS (part I, II, IV), Beliefs about Medication Questionnaire (BMQ), EuroQol (EQ-5D) and the Caregiving Distress Scale. Blinded data were analysed using logistic and linear regression models based on the intention-to-treat principle. Seventy-six patients and 46 spouse/carers completed the study (intervention: n = 38 patients, n = 24 spouse/carers). At week-12 AT significantly improved adherence compared with RC (OR 8.2; 95% CI: 2.8, 24.3). Numbers needed to treat (NNT) were 2.2 (CI: 1.6, 3.9). Compared with RC, AT significantly improved PDQ-39 (-9.0 CI: -12.2, -5.8), BMQ general harm (-1.0 CI: -1.9, -0.2) and MDS-UPDRS part II (-4.8 CI: -8.1, -1.4). No significant interaction was observed between the presence of a spouse/carer and the effect of AT. Adherence Therapy improved self-reported adherence and QoL in a PD sample. The small NNT suggests AT may be cost-effective. A larger pragmatic trial to test the efficacy and cost-effectiveness of AT by multiple therapists is required. © 2014 John Wiley & Sons Ltd.

A randomized clinical trial to evaluate the effects of rasagiline on depressive symptoms in non-demented Parkinson's disease patients.

PubMed

Barone, P; Santangelo, G; Morgante, L; Onofrj, M; Meco, G; Abbruzzese, G; Bonuccelli, U; Cossu, G; Pezzoli, G; Stanzione, P; Lopiano, L; Antonini, A; Tinazzi, M

2015-08-01

Depressed mood is a common psychiatric problem associated with Parkinson's disease (PD), and studies have suggested a benefit of rasagiline treatment. ACCORDO (see the ) was a 12-week, double-blind, placebo-controlled trial to evaluate the effects of rasagiline 1 mg/day on depressive symptoms and cognition in non-demented PD patients with depressive symptoms. The primary efficacy variable was the change from baseline to week 12 in depressive symptoms measured by the Beck Depression Inventory (BDI-IA) total score. Secondary outcomes included change from baseline to week 12 in cognitive function as assessed by a comprehensive neuropsychological battery; Parkinson's disease quality of life questionnaire (PDQ-39) scores; Apathy Scale scores; and Unified Parkinson's Disease Rating Scale (UPDRS) subscores. One hundred and twenty-three patients were randomized. At week 12 there was no significant difference between groups for the reduction in total BDI-IA score (primary efficacy variable). However, analysis at week 4 did show a significant difference in favour of rasagiline (marginal means difference ± SE: rasagiline -5.46 ± 0.73 vs. placebo -3.22 ± 0.67; P = 0.026). There were no significant differences between groups on any cognitive test. Rasagiline significantly improved UPDRS Parts I (P = 0.03) and II (P = 0.003) scores versus placebo at week 12. Post hoc analyses showed the statistical superiority of rasagiline versus placebo in the UPDRS Part I depression item (P = 0.04) and PDQ-39 mobility (P = 0.007) and cognition domains (P = 0.026). Treatment with rasagiline did not have significant effects versus placebo on depressive symptoms or cognition in PD patients with moderate depressive symptoms. Although limited by lack of correction for multiple comparisons, post hoc analyses signalled some improvement in patient-rated cognitive and depression outcomes. © 2015 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.

A randomized clinical trial to evaluate the effects of rasagiline on depressive symptoms in non-demented Parkinson’s disease patients

PubMed Central

Barone, P; Santangelo, G; Morgante, L; Onofrj, M; Meco, G; Abbruzzese, G; Bonuccelli, U; Cossu, G; Pezzoli, G; Stanzione, P; Lopiano, L; Antonini, A; Tinazzi, M

2015-01-01

Background and purpose Depressed mood is a common psychiatric problem associated with Parkinson’s disease (PD), and studies have suggested a benefit of rasagiline treatment. Methods ACCORDO (see the 1) was a 12-week, double-blind, placebo-controlled trial to evaluate the effects of rasagiline 1 mg/day on depressive symptoms and cognition in non-demented PD patients with depressive symptoms. The primary efficacy variable was the change from baseline to week 12 in depressive symptoms measured by the Beck Depression Inventory (BDI-IA) total score. Secondary outcomes included change from baseline to week 12 in cognitive function as assessed by a comprehensive neuropsychological battery; Parkinson’s disease quality of life questionnaire (PDQ-39) scores; Apathy Scale scores; and Unified Parkinson’s Disease Rating Scale (UPDRS) subscores. Results One hundred and twenty-three patients were randomized. At week 12 there was no significant difference between groups for the reduction in total BDI-IA score (primary efficacy variable). However, analysis at week 4 did show a significant difference in favour of rasagiline (marginal means difference ± SE: rasagiline −5.46 ± 0.73 vs. placebo −3.22 ± 0.67; P = 0.026). There were no significant differences between groups on any cognitive test. Rasagiline significantly improved UPDRS Parts I (P = 0.03) and II (P = 0.003) scores versus placebo at week 12. Post hoc analyses showed the statistical superiority of rasagiline versus placebo in the UPDRS Part I depression item (P = 0.04) and PDQ-39 mobility (P = 0.007) and cognition domains (P = 0.026). Conclusions Treatment with rasagiline did not have significant effects versus placebo on depressive symptoms or cognition in PD patients with moderate depressive symptoms. Although limited by lack of correction for multiple comparisons, post hoc analyses signalled some improvement in patient-rated cognitive and depression outcomes. PMID:25962410

MRI directed bilateral stimulation of the subthalamic nucleus in patients with Parkinson's disease

PubMed Central

Patel, N; Plaha, P; O'Sullivan, K; McCarter, R; Heywood, P; Gill, S

2003-01-01

Objective: Bilateral chronic high frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) has emerged as an appropriate therapy for patients with advanced Parkinson's disease refractory to medical therapy. Advances in neuroimaging and neurophysiology have led to the development of varied targeting methods for the delivery of this treatment. Intraoperative neurophysiological and clinical monitoring is regarded by many to be mandatory for accurate STN localisation. We have examined efficacy of bilateral STN stimulation using a predominantly magnetic resonance imaging (MRI)-directed technique. Methods: DBS leads were stereotactically implanted into the STN using an MRI directed method, with intraoperative macrostimulation used purely for adjustment. The effects of DBS were evaluated in 16 patients followed up to 12 months, and compared with baseline assessments. Assessments were performed in both off and on medication states, and were based on the Unified Parkinson's Disease Rating Scale (UPDRS) and timed motor tests. Functional status outcomes were examined using the PDQ-39 quality of life questionnaire. A battery of psychometric tests was used to assess cognition. Results: After 12 months, stimulation in the off medication state resulted in significant improvements in Activities of Daily Living and Motor scores (UPDRS parts II and III) by 62% and 61% respectively. Timed motor tests were significantly improved in the off medication state. Motor scores (UPDRS part III) were significantly improved by 40% in the on medication state. Dyskinesias and off duration were significantly reduced and the mean dose of L-dopa equivalents was reduced by half. Psychometric test scores were mostly unchanged or improved. Adverse events were few. Conclusions: An MRI directed targeting method for implantation of DBS leads into the STN can be used safely and effectively, and results are comparable with studies using intraoperative microelectrode neurophysiological targeting. In addition, our method was associated with an efficient use of operating time, and without the necessary costs of microelectrode recording. PMID:14638880

Effect of bilateral subthalamic electrical stimulation in Parkinson's disease.

PubMed

Broggi, G; Franzini, A; Ferroli, P; Servello, D; D'Incerti, L; Genitrini, S; Soliveri, P; Girotti, F; Caraceni, T

2001-08-01

Bilateral high frequency subthalamic stimulation has been reported to be effective in the treatment of Parkinson's disease and levodopa-induced dyskinesias. To analyze the results of this surgical procedure we critically reviewed 17 parkinsonian patients with advanced disease complicated by motor fluctuations and dyskinesias. Between January 1998 and June 1999 these 17 consecutive patients (age 48-68 years; illness duration 8-27 years) underwent bilateral stereotactically guided implantation of electrodes into the subthalamic nucleus in the Department of Neurosurgery of the Istituto Nazionale Neurologico "C. Besta." Parameters used for continuous high-frequency stimulation were: frequency 160 Hz, pulse width 90 microsec, mean amplitude 2.05 +/- 0.45 V. Parts II and III of the UPDRS were used to assess motor performance before and after operation by the neurologic team. The follow-up ranged between 6 and 18 months. At latest examination, mean UPDRS II and III scores had improved by 30% (on stimulation, off therapy) with mean 50% reduction in daily off time. Peak dyskinesias and early morning dystonias also improved in relation to therapy reduction. Side effects were persistent postoperative supranuclear oculomotor palsy and postural instability in one case, worsened off-medication hypophonia in three, and temporary nocturnal confusion episodes in three. Postoperative MRI revealed a clinically silent intracerebral haematoma in one case. One electrode required repositioning. Continuous high frequency STN stimulation is an effective treatment for advanced PD. A functionally useful and safe electrode placement can be performed without microrecording.

Subthalamus stimulation in Parkinson disease: Accounting for the bilaterality of contacts.

PubMed

Lemaire, Jean-Jacques; Pereira, Bruno; Derost, Philippe; Vassal, François; Ulla, Miguel; Morand, Dominique; Coll, Guillaume; Gabrillargues, Jean; Marques, Ana; Debilly, Bérangère; Coste, Jérôme; Durif, Franck

2016-01-01

Deep brain stimulation (DBS) in Parkinson's disease uses bi-hemispheric high-frequency stimulation within the subthalamus, however, the specific impacts of bilaterality of DBS are still not clear. Thus, we aimed to study the individual-level clinical impact of locations of right-left contact pair-up accounting for each subthalamic nucleus (STN) anatomy. Contact locations and effects at 1 year were studied retrospectively in an unselected series of 53 patients operated between 2004 and 2010. Location of contacts was defined relatively to the main axis of STN used to map longitudinal and transversal positions, and STN membership (out meaning out-of-STN). Contact pairings were described via three methods: (i) Unified contact location (UCL) collapsing DBS into an all-in-one contact; (ii) balance of contact pair-up (BCPU), defined as symmetric or asymmetric regardless of laterality; (iii) hemisphere-wise most frequent contact pair-up (MFCP) regardless of BCPU. Clinical data were: mean levodopa equivalent dose, Unified Parkinson's Disease Rating Scale (UPDRS) motor score III without medication, UPDRS II and III speech sub-scores, UPDRS II freezing sub-score, 1 year versus preoperative values, with and without levodopa. Ad-hoc two-sided tests were used for statistical analysis. Worsening speech, was more frequent for UCL_out patients and when the left MFCP contact was rear and/or superolateral, however, it less frequent for BCPU-asymmetric patients. Worsening freezing was more frequent when the right MFCP contact was rear and superolateral. These results point to strategies for minimizing dysarthria and freezing as adverse effects of DBS.

Subthalamus stimulation in Parkinson disease: Accounting for the bilaterality of contacts

PubMed Central

Lemaire, Jean-Jacques; Pereira, Bruno; Derost, Philippe; Vassal, François; Ulla, Miguel; Morand, Dominique; Coll, Guillaume; Gabrillargues, Jean; Marques, Ana; Debilly, Bérangère; Coste, Jérôme; Durif, Franck

2016-01-01

Background: Deep brain stimulation (DBS) in Parkinson's disease uses bi-hemispheric high-frequency stimulation within the subthalamus, however, the specific impacts of bilaterality of DBS are still not clear. Thus, we aimed to study the individual-level clinical impact of locations of right-left contact pair-up accounting for each subthalamic nucleus (STN) anatomy. Methods: Contact locations and effects at 1 year were studied retrospectively in an unselected series of 53 patients operated between 2004 and 2010. Location of contacts was defined relatively to the main axis of STN used to map longitudinal and transversal positions, and STN membership (out meaning out-of-STN). Contact pairings were described via three methods: (i) Unified contact location (UCL) collapsing DBS into an all-in-one contact; (ii) balance of contact pair-up (BCPU), defined as symmetric or asymmetric regardless of laterality; (iii) hemisphere-wise most frequent contact pair-up (MFCP) regardless of BCPU. Clinical data were: mean levodopa equivalent dose, Unified Parkinson's Disease Rating Scale (UPDRS) motor score III without medication, UPDRS II and III speech sub-scores, UPDRS II freezing sub-score, 1 year versus preoperative values, with and without levodopa. Ad-hoc two-sided tests were used for statistical analysis. Results: Worsening speech, was more frequent for UCL_out patients and when the left MFCP contact was rear and/or superolateral, however, it less frequent for BCPU-asymmetric patients. Worsening freezing was more frequent when the right MFCP contact was rear and superolateral. Conclusions: These results point to strategies for minimizing dysarthria and freezing as adverse effects of DBS. PMID:27990316

High-dose transdermal nicotine in Parkinson's disease patients: a randomized, open-label, blinded-endpoint evaluation phase 2 study.

PubMed

Villafane, G; Thiriez, C; Audureau, E; Straczek, C; Kerschen, P; Cormier-Dequaire, F; Van Der Gucht, A; Gurruchaga, J-M; Quéré-Carne, M; Evangelista, E; Paul, M; Defer, G; Damier, P; Remy, P; Itti, E; Fénelon, G

2018-01-01

Studies of the effects of nicotine on motor symptoms in Parkinson's disease (PD) brought out discordant results. The aim of the present study was to evaluate the efficacy and safety of high doses of transdermal nicotine on motor symptoms in PD. Forty PD patients were randomly assigned to a treated and untreated arm in an open-label study. Treated patients received increasing doses of nicotine to reach 90 mg/day by 11 weeks. This dosage was maintained for 28 weeks (W39) and then reduced over 6 weeks. Final evaluation was performed 6 weeks after washout. The main outcome measure was the OFF-DOPA Unified Parkinson's Disease Rating Scale (UPDRS) motor score measured on video recordings by raters blinded to the medication status of the patients. There was no significant difference in OFF-DOPA UPDRS motor scores between the nicotine-treated and non-treated groups, neither at W39 (19.4 ± 9.3 vs. 21.5 ± 14.2) nor considering W39 differences from baseline (-1.5 ± 12.1 vs. +0.9 ± 12.1). The 39-item Parkinson's disease questionnaire scores decreased in nicotine-treated patients and increased in non-treated patients, but the difference was not significant. Overall tolerability was acceptable, and 12/20 treated patients reached the maximal dosage. High doses of transdermal nicotine were tolerated, but our study failed to demonstrate significant improvement in UPDRS motor scores. Improvement in unblinded secondary outcomes (UPDRS-II, UPDRS-IV, doses of l-DOPA equivalents) suggest a possible benefit for patients treated with nicotine, which should be confirmed in larger double blind, placebo-controlled studies. © 2017 EAN.

Differential effects of deep brain stimulation target on motor subtypes in Parkinson's disease.

PubMed

Katz, Maya; Luciano, Marta San; Carlson, Kimberly; Luo, Ping; Marks, William J; Larson, Paul S; Starr, Philip A; Follett, Kenneth A; Weaver, Frances M; Stern, Matthew B; Reda, Domenic J; Ostrem, Jill L

2015-04-01

The Veterans Administration Cooperative Studies Program #468, a multicenter study that randomized Parkinson's disease (PD) patients to either subthalamic nucleus (STN) or globus pallidus internus (GPi) deep brain stimulation (DBS), found that stimulation at either target provided similar overall motoric benefits. We conducted an additional analysis of this data set to evaluate whether PD motor subtypes responded differently to the 2 stimulation targets. We classified 235 subjects by motor subtype: tremor dominant (TD), intermediate (I), or postural instability gait difficulty (PIGD), based on pre-DBS baseline Unified Parkinson's Disease Rating Scale (UPDRS) scores off-medication. The primary outcome was change in UPDRS part III (UPDRS-III) off-medication scores from baseline to 24 months post-DBS, compared among subjects with particular PD motor subtypes and by DBS target (STN vs GPi). Changes in tremor, rigidity, akinesia, and gait scores were also assessed using the UPDRS. TD patients had greater mean overall motor improvement, measured by UPDRS-III, after GPi DBS, compared to STN DBS (17.5 ± 13.0 vs 14.6 ± 14.9, p = 0.02), with improvement in gait accounting for this difference. Regardless of stimulation target, PIGD subjects had lower mean overall improvement in UPDRS-III scores compared with I or TD subjects (8.7 ± 12.2 vs 21.7 ± 11.2 vs 16.3 ± 13.8, p = 0.001). Our results suggest that responsiveness to both GPi and STN DBS is similar among different PD motor subtypes, although the TD motor subtype may have a greater response to GPi DBS with respect to gait. PIGD patients obtained less overall benefit from stimulation. © 2015 American Neurological Association.

Potential reliability and validity of a modified version of the Unified Parkinson’s Disease Rating Scale that could be administered remotely

PubMed Central

Abdolahi, Amir; Scoglio, Nicholas; Killoran, Annie; Dorsey, Ray; Biglan, Kevin M.

2013-01-01

Background By permitting remote assessments of patients and research participants, telemedicine has the potential to reshape clinical care and clinical trials for Parkinson disease. While the majority of the motor Unified Parkinson’s Disease Rating Scale (UPDRS) items can be conducted visually, rigidity and retropulsion pull testing require hands-on assessment by the rater and are less feasible to perform remotely in patients' homes. Methods In a secondary data analysis of the Comparison of the Agonist pramipexole vs. Levodopa on Motor complications in Parkinson’s Disease (CALM-PD) study, a randomized clinical trial, we assessed the cross-sectional (baseline and 2 years) and longitudinal (change from baseline to 2 years) reliability of a modified motor UPDRS (removing rigidity and retropulsion items) compared to the standard motor UPDRS (all items) using intraclass correlation coefficients (ICC), stratified by treatment group. Internal consistency of the modified UPDRS (mUPDRS) was measured using Cronbach’s alpha, and concurrent validity was assessed using Pearson’s correlation coefficient (r) between the standard motor UPDRS and mUPDRS. Results The mUPDRS versus standard motor UPDRS is cross-sectionally (ICC ≥ 0.92) and longitudinally (ICC ≥ 0.92) reliable for both treatment groups. High internal consistencies were also observed (α ≥ 0.96). The mUPDRS had high concurrent validity with the standard UPDRS at both time points and longitudinally (r ≥ 0.93, p < 0.0001). Conclusions A modified version of the motor UPDRS without rigidity and retropulsion pull testing is reliable and valid and may lay the foundation for its use in remote assessments of patients and research participants. PMID:23102808

Potential reliability and validity of a modified version of the Unified Parkinson's Disease Rating Scale that could be administered remotely.

PubMed

Abdolahi, Amir; Scoglio, Nicholas; Killoran, Annie; Dorsey, E Ray; Biglan, Kevin M

2013-02-01

By permitting remote assessments of patients and research participants, telemedicine has the potential to reshape clinical care and clinical trials for Parkinson disease. While the majority of the motor Unified Parkinson's Disease Rating Scale (UPDRS) items can be conducted visually, rigidity and retropulsion pull testing require hands-on assessment by the rater and are less feasible to perform remotely in patients' homes. In a secondary data analysis of the Comparison of the Agonist pramipexole vs. Levodopa on Motor complications in Parkinson's Disease (CALM-PD) study, a randomized clinical trial, we assessed the cross-sectional (baseline and 2 years) and longitudinal (change from baseline to 2 years) reliability of a modified motor UPDRS (removing rigidity and retropulsion items) compared to the standard motor UPDRS (all items) using intraclass correlation coefficients (ICC), stratified by treatment group. Internal consistency of the modified UPDRS (mUPDRS) was measured using Cronbach's alpha, and concurrent validity was assessed using Pearson's correlation coefficient (r) between the standard motor UPDRS and mUPDRS. The mUPDRS versus standard motor UPDRS is cross-sectionally (ICC ≥ 0.92) and longitudinally (ICC ≥ 0.92) reliable for both treatment groups. High internal consistencies were also observed (α ≥ 0.96). The mUPDRS had high concurrent validity with the standard UPDRS at both time points and longitudinally (r ≥ 0.93, p < 0.0001). A modified version of the motor UPDRS without rigidity and retropulsion pull testing is reliable and valid and may lay the foundation for its use in remote assessments of patients and research participants. Copyright © 2012 Elsevier Ltd. All rights reserved.

Evaluation of Parkinson's disease by neuromelanin-sensitive magnetic resonance imaging and 123I-FP-CIT SPECT.

PubMed

Kuya, Keita; Ogawa, Toshihide; Shinohara, Yuki; Ishibashi, Mana; Fujii, Shinya; Mukuda, Naoko; Tanabe, Yoshio

2018-05-01

Background Both neuromelanin-sensitive magnetic resonance imaging (NmMRI) and 123 I-FP-CIT single photon emission computed tomography (SPECT) (DaTSCAN) assist the diagnosis of Parkinson's disease (PD). However, there have been few studies investigating a correlation between them. Purpose To correlate the utility of NmMRI and DaTSCAN and to evaluate the relationship between both imaging findings and the Unified PD rating scale part III (UPDRS III) score for the diagnosis and management of PD. Material and Methods Seventeen patients with PD who underwent both NmMRI and DaTSCAN were included. We measured the volume of the neuromelanin-positive substantia nigra pars compacta (SNc volume) on NmMRI and measured the specific binding ratio (SBR) on DaTSCAN. The asymmetry index (AI) of the SNc volume and SBR were also calculated. We evaluated the relationship between the UPDRS III score and the SNc volume and SBR, respectively. Results The SNc volume showed a significant correlation with the SBR. The AIs of them also showed a significant correlation. Both the mean of the bilateral SBR and the mean of the bilateral SNc volume showed significant negative correlations with the UPDRS III score. However, the correlation between the SBR and the UPDRS III score was stronger than that between the SNc volume and the UPDRS III score. Conclusion Both NmMRI and DaTSCAN are helpful for PD diagnosis. However, we conclude that DaTSCAN is more suitable for the evaluation of the clinical motor severity and would be more useful for the management of PD patients than NmMRI.

Laughter is the best medicine: The Second City® improvisation as an intervention for Parkinson's disease.

PubMed

Bega, Danny; Palmentera, Pamela; Wagner, Abby; Hovde, Matt; Barish, Becca; Kwasny, Mary J; Simuni, Tanya

2017-01-01

Expressive therapies are increasingly incorporated into the management of Parkinson's disease (PD), although there are little objective data assessing their benefits. Develop and study a novel community Improvisation Theater (IT) program for PD in order to improve quality of life. A prospective, rater-blinded, modified cross-over design study of IT for PD. 22 subjects were randomized 1:1 to active-start (AS) or control-start (CS) groups, controlling for age and Hoehn and Yahr stage. Participants were recruited from the Northwestern PD and Movement Disorders Center. 60 min IT sessions were led by The Second City ® faculty weekly for 12 weeks. The primary aim was to assess feasibility, determined as 70% of participants attending at least 75% of the classes. Exploratory data were obtained comparing pre- and post-intervention outcomes using Wilcoxon signed rank test for UPDRS parts I-IV, PDQ-39, and 5 neuro-QoL measures (communication, anxiety, stigma, depression, and wellbeing). All 22 participants completed the study. 21/22 (95%) participants attended at least 80% of the classes. All participants indicated that they would recommend the class to others with PD. 21/22 participants enjoyed the class and felt it was beneficial for their symptoms. A significant improvement pre-to-post intervention was seen with the UPDRS part II ADL measure (mean -1.5, p = 0.019). A novel improvisation program can be well-attended, enjoyable, and improve ADL measures among patients with PD of varying ages and disease severity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cross-Cultural Differences of the Non-Motor Symptoms Studied by the Traditional Chinese Version of the International Parkinson and Movement Disorder Society- Unified Parkinson's Disease Rating Scale.

PubMed

Yu, Rwei-Ling; Wu, Ruey-Meei; Chan, Anne Y Y; Mok, Vincent; Wu, Yih-Ru; Tilley, Barbara C; Luo, Sheng; Wang, Lu; LaPelle, Nancy R; Stebbins, Glenn T; Goetz, Christopher G

2017-01-01

Given the importance of ethnic differences in the evaluation of various aspects of symptoms in patients with Parkinson's disease (PD), we present the formal procedure for completing the traditional Chinese translation of the International and Parkinson and Movement Disorder Society/UPDRS (MDS-UPDRS) and highlight the discrepancy in nonmotor symptoms (NMS) between patients in Eastern and Western countries. A total of 350 native Chinese-speaking PD patients were recruited from multiple hospitals in Eastern countries; they completed the MDS-UPDRS. The translation process was executed and factor analysis was performed to determine the structure of the scale. Chi-squared and t tests were used to compare frequency and severity of PD symptoms between the Chinese-speaking and English-speaking groups (n = 876). NMS and motor symptoms were more severe in the Western population (Part I: t (1205) = 5.36, P < 0.0001; and Part III: t (1205) = 7.64, P < 0.0001); however, the prevalence of cognitive dysfunction and impairments in activities of daily living were more frequent in the Eastern patients. The comparative fit index was 0.93 or greater, and the exploratory factor analysis revealed compatible results between the translated scale and the original version. The traditional Chinese version of the MDS-UPDRS can be designated as an official translation of the original scale, and it is now available for use. Moreover, NMS in PD constitute a major issue worldwide, and the pattern of NMS among the Chinese population is more marked in terms of cognition-based symptoms and activities of daily living.

Motor associations of iron accumulation in deep grey matter nuclei in Parkinson's disease: a cross-sectional study of iron-related magnetic resonance imaging susceptibility.

PubMed

Martin-Bastida, A; Lao-Kaim, N P; Loane, C; Politis, M; Roussakis, A A; Valle-Guzman, N; Kefalopoulou, Z; Paul-Visse, G; Widner, H; Xing, Y; Schwarz, S T; Auer, D P; Foltynie, T; Barker, R A; Piccini, P

2017-02-01

To determine whether iron deposition in deep brain nuclei assessed using high-pass filtered phase imaging plays a role in motor disease severity in Parkinson's disease (PD). Seventy patients with mild to moderate PD and 20 age- and gender-matched healthy volunteers (HVs) underwent susceptibility-weighted imaging on a 3 T magnetic resonance imaging scanner. Phase shifts (radians) in deep brain nuclei were derived from high-pass filtered phase images and compared between groups. Analysis of clinical laterality and correlations with motor severity (Unified Parkinson's Disease Rating Scale, Part III, UPDRS-III) were performed. Phase shifts (in radians) were compared between HVs and three PD subgroups divided according to UPDRS-III scores using analysis of covariance, adjusting for age and regional area. Parkinson's disease patients had significantly (P < 0.001) higher radians than HVs bilaterally in the putamen, globus pallidus and substantia nigra (SN). The SN contralateral to the most affected side showed higher radians (P < 0.001) compared to the less affected side. SN radians positively correlated with UPDRS-III and bradykinesia-rigidity subscores, but not with tremor subscores. ancova followed by post hoc Bonferroni-adjusted pairwise comparisons revealed that SN radians were significantly greater in the PD subgroup with higher UPDRS-III scores compared to both lowest UPDRS-III PD and HV groups (P < 0.001). Increased nigral iron accumulation in PD appears to be stratified according to disease motor severity and correlates with symptoms related to dopaminergic neurodegeneration. This semi-quantitative in vivo iron assessment could prove useful for objectively monitoring PD progression, especially in clinical trials concerning iron chelation therapies. © 2016 EAN.

Gender-, age-, and race/ethnicity-based differential item functioning analysis of the movement disorder society-sponsored revision of the Unified Parkinson's disease rating scale.

PubMed

Goetz, Christopher G; Liu, Yuanyuan; Stebbins, Glenn T; Wang, Lu; Tilley, Barbara C; Teresi, Jeanne A; Merkitch, Douglas; Luo, Sheng

2016-12-01

Assess MDS-UPDRS items for gender-, age-, and race/ethnicity-based differential item functioning. Assessing differential item functioning is a core rating scale validation step. For the MDS-UPDRS, differential item functioning occurs if item-score probability among people with similar levels of parkinsonism differ according to selected covariates (gender, age, race/ethnicity). If the magnitude of differential item functioning is clinically relevant, item-score interpretation must consider influences by these covariates. Differential item functioning can be nonuniform (covariate variably influences an item-score across different levels of parkinsonism) or uniform (covariate influences an item-score consistently over all levels of parkinsonism). Using the MDS-UPDRS translation database of more than 5,000 PD patients from 14 languages, we tested gender-, age-, and race/ethnicity-based differential item functioning. To designate an item as having clinically relevant differential item functioning, we required statistical confirmation by 2 independent methods, along with a McFadden pseudo-R 2 magnitude statistic greater than "negligible." Most items showed no gender-, age- or race/ethnicity-based differential item functioning. When differential item functioning was identified, the magnitude statistic was always in the "negligible" range, and the scale-level impact was minimal. The absence of clinically relevant differential item functioning across all items and all parts of the MDS-UPDRS is strong evidence that the scale can be used confidently. As studies of Parkinson's disease increasingly involve multinational efforts and the MDS-UPDRS has several validated non-English translations, the findings support the scale's broad applicability in populations with varying gender, age, and race/ethnicity distributions. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

The safety and tolerability of rotigotine transdermal system over a 6-year period in patients with early-stage Parkinson's disease.

PubMed

Giladi, Nir; Boroojerdi, Babak; Surmann, Erwin

2013-09-01

This open-label extension (SP716; NCT00599196) of a 6-month, double-blind, randomized study (SP513) investigated the safety and tolerability of rotigotine transdermal system over up to ~6 years in patients with Parkinson's disease (PD; early-stage PD at double-blind enrollment). Eligible patients completing the 6-month study received optimal dose open-label rotigotine (≤ 16 mg/24 h) for up to ~6 years. Adjunctive levodopa was permitted. Primary outcomes included adverse events (AEs) and extent of rotigotine exposure. Analysis of adjunctive levodopa use, dyskinesias [unified Parkinson's disease rating scale (UPDRS) IV], and efficacy (UPDRS II + III total score) were also assessed. Of 381 patients enrolled in the open-label extension, 52 % were still in the study at time of closure; 24 % withdrew because of AEs and 6 % because of lack of efficacy. Patients received rotigotine for a median duration of 1,564.5 days (~4 years, 3 months; range 5-2, 145 days). 69 % of patients started supplemental levodopa; median time to levodopa was 485 days (~1 year, 4 months). Most common AEs (% per patient-year) were somnolence (18 %), application site reactions (12 %), nausea (9 %), peripheral edema (7 %), and fall (7 %). AEs indicative of impulsive-compulsive behavior were recorded in 25 (7 %) patients. Dyskinesias were experienced by 65 (17 %) patients; the majority [47 of 65 (72 %)] reported first dyskinesia after starting levodopa. Mean UPDRS II + III total scores remained below double-blind baseline for 4 years (assessment of all patients). In conclusion, rotigotine was generally well tolerated for up to ~6 years in patients with early-stage PD. The AEs reported were in line with previous studies of rotigotine transdermal system, with typical dopaminergic side effects and application site reactions seen.

Rasagiline for mild cognitive impairment in Parkinson's disease: A placebo-controlled trial.

PubMed

Weintraub, Daniel; Hauser, Robert A; Elm, Jordan J; Pagan, Fernando; Davis, Matthew D; Choudhry, Azhar

2016-05-01

This study's aims were to determine the efficacy and tolerability of rasagiline, a selective monoamine oxidase inhibitor B, for PD patients with mild cognitive impairment. Patients on stable dopaminergic therapy were randomized to adjunct rasagiline 1 mg/day or placebo in this 24-week, double-blind, placebo-controlled, multisite study. The primary endpoint was mean change from baseline to week 24 on the Scales for Outcomes of Parkinson's Disease-Cognition total score. Key secondary measures included changes in cognition, activities of daily living, motor scores, and Clinical Global Impression of Change, as well as safety and tolerability measures. Of the 170 patients randomized, 151 (88.2%) completed the study. Change in Scales for Outcomes of Parkinson's Disease-Cognition scores were not significantly different in the rasagiline and placebo groups (adjusted mean: 1.6 [standard error {SE} = 0.5] vs. 0.8 [SE = 0.5] points; LS means difference = 0.8; 95% confidence interval: -0.48, 2.05; P = 0.22). There were no between-group differences in change in the MoCA (p=0.84) or Penn Daily Activities Questionnaire (P = 0.48) scores or in the distribution of Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change modified for mild cognitive impairment (P = 0.1). Changes in motor (UPDRS part III; P = 0.02) and activities of daily living (UPDRS part II; P < 0.001) scores favored rasagiline. Rasagiline was well tolerated; the most common adverse events in both groups were falls and dizziness. Rasagiline treatment in PD patients with mild cognitive impairment was not associated with cognitive improvement. Rasagiline did not worsen cognition, improved motor symptoms and activities of daily living, and was well tolerated in elderly cognitively impaired patients. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Subthalamic nucleus deep brain stimulation for Parkinson's disease: evidence for effectiveness and limitations from 12 years' experience.

PubMed

Chan, Anne Y Y; Yeung, Jonas H M; Mok, Vincent C T; Ip, Vincent H L; Wong, Adrian; Kuo, S H; Chan, Danny T M; Zhu, X L; Wong, Edith; Lau, Claire K Y; Wong, Rosanna K M; Tang, Venus; Lau, Christine; Poon, W S

2014-12-01

To present the result and experience of subthalamic nucleus deep brain stimulation for Parkinson's disease. Case series. Prince of Wales Hospital, Hong Kong. A cohort of patients with Parkinson's disease received subthalamic nucleus deep brain stimulation from September 1998 to January 2010. Patient assessment data before and after the operation were collected prospectively. Forty-one patients (21 male and 20 female) with Parkinson's disease underwent bilateral subthalamic nucleus deep brain stimulation and were followed up for a median interval of 12 months. For the whole group, the mean improvements of Unified Parkinson's Disease Rating Scale (UPDRS) parts II and III were 32.5% and 31.5%, respectively (P<0.001). Throughout the years, a multidisciplinary team was gradually built. The deep brain stimulation protocol evolved and was substantiated by updated patient selection criteria and outcome assessment, integrated imaging and neurophysiological targeting, refinement of surgical technique as well as the accumulation of experience in deep brain stimulation programming. Most of the structural improvement occurred before mid-2005. Patients receiving the operation before June 2005 (19 cases) and after (22 cases) were compared; the improvements in UPDRS part III were 13.2% and 55.2%, respectively (P<0.001). There were three operative complications (one lead migration, one cerebral haematoma, and one infection) in the group operated on before 2005. There was no operative mortality. The functional state of Parkinson's disease patients with motor disabilities refractory to best medical treatment improved significantly after subthalamic nucleus deep brain stimulation. A dedicated multidisciplinary team building, refined protocol for patient selection and assessment, improvement of targeting methods, meticulous surgical technique, and experience in programming are the key factors contributing to the improved outcome.

Deep brain stimulation may reduce the relative risk of clinically important worsening in early stage Parkinson's disease.

PubMed

Hacker, Mallory L; Tonascia, James; Turchan, Maxim; Currie, Amanda; Heusinkveld, Lauren; Konrad, Peter E; Davis, Thomas L; Neimat, Joseph S; Phibbs, Fenna T; Hedera, Peter; Wang, Lily; Shi, Yaping; Shade, David M; Sternberg, Alice L; Drye, Lea T; Charles, David

2015-10-01

The Vanderbilt pilot trial of deep brain stimulation (DBS) in early Parkinson's disease (PD) enrolled patients on medications six months to four years without motor fluctuations or dyskinesias. We conducted a patient-centered analysis based on clinically important worsening of motor symptoms and complications of medical therapy for all subjects and a subset of subjects with a more focused medication duration. Continuous outcomes were also analyzed for this focused cohort. A post hoc analysis was conducted on all subjects from the pilot and a subset of subjects taking PD medications 1-4 years at enrollment. Clinically important worsening is defined as both a ≥ 3 point increase in UPDRS Part III and a ≥ 1 point increase in Part IV. DBS plus optimal drug therapy (DBS + ODT) subjects experienced a 50-80% reduction in the relative risk of worsening after two years. The DBS + ODT group was improved compared to optimal drug therapy (ODT) at each time point on Total UPDRS and Part III (p = 0.04, p = 0.02, respectively, at 24 months). Total UPDRS, Part IV, and PDQ-39 scores significantly worsened in the ODT group after two years (p < 0.003), with no significant change in the DBS + ODT group. DBS + ODT in early PD may reduce the risk of clinically important worsening. These findings further confirm the need to determine if DBS + ODT is superior to medical therapy for managing symptoms, reducing the complications of medications, and improving quality of life. The FDA has approved the conduct of a large-scale, pivotal clinical trial of DBS in early stage PD. Copyright © 2015 Elsevier Ltd. All rights reserved.

Analysis and Visualization of 3D Motion Data for UPDRS Rating of Patients with Parkinson's Disease.

PubMed

Piro, Neltje E; Piro, Lennart K; Kassubek, Jan; Blechschmidt-Trapp, Ronald A

2016-06-21

Remote monitoring of Parkinson's Disease (PD) patients with inertia sensors is a relevant method for a better assessment of symptoms. We present a new approach for symptom quantification based on motion data: the automatic Unified Parkinson Disease Rating Scale (UPDRS) classification in combination with an animated 3D avatar giving the neurologist the impression of having the patient live in front of him. In this study we compared the UPDRS ratings of the pronation-supination task derived from: (a) an examination based on video recordings as a clinical reference; (b) an automatically classified UPDRS; and (c) a UPDRS rating from the assessment of the animated 3D avatar. Data were recorded using Magnetic, Angular Rate, Gravity (MARG) sensors with 15 subjects performing a pronation-supination movement of the hand. After preprocessing, the data were classified with a J48 classifier and animated as a 3D avatar. Video recording of the movements, as well as the 3D avatar, were examined by movement disorder specialists and rated by UPDRS. The mean agreement between the ratings based on video and (b) the automatically classified UPDRS is 0.48 and with (c) the 3D avatar it is 0.47. The 3D avatar is similarly suitable for assessing the UPDRS as video recordings for the examined task and will be further developed by the research team.

Hyperbaric oxygen treatment for Parkinson's disease with severe depression and anxiety: A case report.

PubMed

Xu, Jin-Jin; Yang, Si-Tong; Sha, Ying; Ge, Yuan-Yuan; Wang, Jian-Meng

2018-03-01

Patients with Parkinson's disease (PD) frequently suffer from psychiatric disorders, and treating these symptom whereas managing the motor symptoms associated with PD can be a therapeutic challenge. We report a case of PD patient with severe depression and anxiety that refused to be treated with dopaminagonists or SSRIs, the most common treatments for PD patients suffering from psychiatric symptoms. Parkinson's disease with severe depression and anxiety. This man was treated with hyperbaric oxygen treatment for 30 days. Clinical assessment scores for depression and anxiety, including Unified Parkinson's Disease Rating ScaleI (UPDRS I), UPDRS II, Hanmilton Depression Rating Scale, and Hamiliton Anxiety Rating Scale, were improved following the hyperbaric oxygen treatment. Hyperbaric oxygen treatment may be a potential therapeutic method for PD patient suffering from depression and anxiety. Further research is needed to validate this finding and explore a potential mechanism.

Parkinsonism signs and symptoms in agricultural pesticide handlers in Washington State

PubMed Central

Nielsen, Susan Searles; Hu, Shu-Ching; Checkoway, Harvey; Negrete, Maria; Palmández, Pablo; Bordianu, Theresa; Racette, Brad A.; Simpson, Christopher D.

2017-01-01

Objectives Examine associations between pesticide exposure and signs or symptoms of parkinsonism. Methods Prior to the 2014 pesticide spray season we examined 38 active pesticide handlers age 35-65 (median 43.5) who participated in the State of Washington's cholinesterase monitoring program in the Yakima Valley, where cholinesterase-inhibiting insecticides are applied in fruit orchards. A movement disorders specialist assessed the workers using the Unified Parkinson's Disease Rating Scale (UPDRS) motor subscore 3 (UPDRS3). Participants also self-reported work and medical histories, including the UPDRS activities of daily living subscore 2 (UPDRS2). We explored the relation between these scores and lifetime occupational pesticide exposure while accounting for age. Results All participants were Hispanic men born in Mexico who had worked in agriculture for 4-43 years (median 21 years, including 11 years applying pesticides, mostly in the U.S.). Ten participants (26%) reported difficulty with one or more UPDRS2 activities of daily living (maximum=2) and nine (24%) had a UPDRS3>0 (maximum=10). The most common symptom and sign, respectively, were excess saliva (n=6) and action tremor (n=5). UPDRS2 and UPDRS3 scores were unrelated to the number of years applying pesticides, but UPDRS3, especially action tremor, was positively associated with living on or by a farm. Conclusions Symptoms and signs of parkinsonism were absent to mild in this small sample of active workers who apply cholinesterase-inhibiting insecticides in Washington State, U.S. Future studies should be larger, and examine older, retired workers with greater cumulative exposure to agricultural pesticides at work and home, including other types of agricultural pesticides. PMID:28418778

Parkinsonism Signs and Symptoms in Agricultural Pesticide Handlers in Washington State.

PubMed

Searles Nielsen, Susan; Hu, Shu-Ching; Checkoway, Harvey; Negrete, Maria; Palmández, Pablo; Bordianu, Theresa; Racette, Brad A; Simpson, Christopher D

2017-01-01

Examine associations between pesticide exposure and signs or symptoms of parkinsonism. Prior to the 2014 pesticide spray season, the authors examined 38 active pesticide handlers aged 35 to 65 (median: 43.5) who participated in the State of Washington's cholinesterase monitoring program in the Yakima Valley, where cholinesterase-inhibiting insecticides are applied in fruit orchards. A movement disorder specialist assessed the workers using the Unified Parkinson's Disease Rating Scale (UPDRS) motor subscore 3 (UPDRS3). Participants also self-reported work and medical histories, including the UPDRS activities of daily living subscore 2 (UPDRS2). The authors explored the relation between these scores and lifetime occupational pesticide exposure while accounting for age. All participants were Hispanic men born in Mexico who had worked in agriculture for 4 to 43 years (median: 21 years, including 11 years applying pesticides, mostly in the United States). Ten participants (26%) reported difficulty with one or more UPDRS2 activities of daily living (maximum = 2), and nine (24%) had a UPDRS3 >0 (maximum = 10). The most common symptom and sign, respectively, were excess saliva (n = 6) and action tremor (n = 5). UPDRS2 and UPDRS3 scores were unrelated to the number of years applying pesticides, but UPDRS3, especially action tremor, was positively associated with living on or by a farm. Symptoms and signs of parkinsonism were absent to mild in this small sample of active workers who apply cholinesterase-inhibiting insecticides in Washington State, USA. Future studies should be larger and examine older, retired workers with greater cumulative exposure to agricultural pesticides at work and home, including other types of agricultural pesticides.

Physical Therapy Versus a General Exercise Programme in Patients with Hoehn Yahr Stage II Parkinson's Disease: A Randomized Controlled Trial.

PubMed

Dipasquale, Savina; Meroni, Roberto; Sasanelli, Francesco; Messineo, Ivan; Piscitelli, Daniele; Perin, Cecilia; Cornaggia, Cesare Maria; Cerri, Cesare G

2017-01-01

Several studies suggest that general exercise (GE) and physical therapy programmes (PT) improve the outcomes of Parkinson's disease (PD) patients; however, the available data do not allow a determination of which treatment is more effective. Our study aims to compare the effects of physiotherapy and general exercise in Parkinson's disease. Design and setting: Randomized controlled trial -general hospital outpatient clinic. The participants were patients with Hoehn Yahr stage II PD. Two randomized groups: one receiving PT and one receiving GE. The outcome measures were the FIM, Hamilton Rating Scale, TUG test, and UPDRS. FIM median scores improved by 3 points in the PT group after treatment, and the improvements were maintained at follow-up. The GE FIM median scores were unchanged after treatment and were reduced by 1 point at follow-up (p < 0.05). The TUG test time was reduced in the PT group but increased in the GE group with a 3-second difference between groups at follow-up, suggesting improved functional mobility after specific physiotherapy (p < 0.05). The UPDRS median score change from baseline was significantly different between the two groups at the end of treatment (6.5 points) and at follow-up (11 points), with a benefit for the physiotherapy group. Physiotherapy seems to be more effective than a generic exercise programme in patients with Hoehn Yahr stage II PD.

Randomized trial of preladenant, given as monotherapy, in patients with early Parkinson disease.

PubMed

Stocchi, Fabrizio; Rascol, Olivier; Hauser, Robert A; Huyck, Susan; Tzontcheva, Anjela; Capece, Rachel; Ho, Tony W; Sklar, Peter; Lines, Christopher; Michelson, David; Hewitt, David J

2017-06-06

To evaluate the adenosine 2a receptor antagonist preladenant as a nondopaminergic drug for the treatment of Parkinson disease (PD) when given as monotherapy. This was a randomized, 26-week, placebo- and active-controlled, parallel-group, multicenter, double-blind trial conducted in adults diagnosed with PD for <5 years who were not yet receiving l-dopa or dopamine agonists. Patients with a Unified Parkinson's Disease Rating Scale (UPDRS) part 3 (motor function) score ≥10 and Hoehn & Yahr score ≤3 were randomized 1:1:1:1:1 to preladenant 2, 5, or 10 mg twice daily, rasagiline 1 mg (active-control) once daily, or placebo. The primary endpoint was the change from baseline at week 26 in the sum of UPDRS parts 2 (activities of daily living) and 3 scores (UPDRS 2+3 ). The number of patients treated was 1,007. Neither preladenant nor rasagiline was superior to placebo after 26 weeks. The differences vs placebo (95% confidence interval) in UPDRS 2+3 scores (with a negative difference indicating improvement vs placebo) were preladenant 2 mg = 2.60 (0.86, 4.30), preladenant 5 mg = 1.30 (-0.41, 2.94), preladenant 10 mg = 0.40 (-1.29, 2.11), and rasagiline 1 mg = 0.30 (-1.35, 2.03). Post hoc analyses did not identify a single causal factor that could explain the finding of a failed trial. Preladenant was generally well-tolerated with few patients discontinuing due to adverse events (preladenant 7%, rasagiline 3%, placebo 4%). No evidence supporting the efficacy of preladenant as monotherapy was observed in this phase 3 trial. The lack of efficacy of the active control rasagiline makes it difficult to interpret the results. Clinicaltrials.gov: NCT01155479. This study provides Class I evidence that for patients with early PD, preladenant is not effective as monotherapy at the doses studied (2, 5, 10 mg). © 2017 American Academy of Neurology.

Comparison of the Efficacy of Different Drugs on Non-Motor Symptoms of Parkinson's Disease: a Network Meta-Analysis.

PubMed

Li, Bao-Dong; Cui, Jing-Jun; Song, Jia; Qi, Ce; Ma, Pei-Feng; Wang, Ya-Rong; Bai, Jing

2018-01-01

A network meta-analysis is used to compare the efficacy of ropinirole, rasagiline, rotigotine, entacapone, apomorphine, pramipexole, sumanirole, bromocriptine, piribedil and levodopa, with placebo as a control, for non-motor symptoms in Parkinson's disease (PD). PubMed, Embase and the Cochrane Library were searched from their establishment dates up to January 2017 for randomized controlled trials (RCTs) investigating the efficacy of the above ten drugs on the non-motor symptoms of PD. A network meta-analysis combined the evidence from direct comparisons and indirect comparisons and evaluated the pooled weighted mean difference (WMD) values and surfaces under the cumulative ranking curves (SUCRA). The network meta-analysis included 21 RCTs. The analysis results indicated that, using the United Parkinson's Disease Rating Scale (UPDRS) III, the efficacies of placebo, ropinirole, rasagiline, rotigotine, entacapone, pramipexole, sumanirole and levodopa in treating PD were lower than that of apomorphine (WMD = -10.90, 95% CI = -16.12∼-5.48; WMD = -11.85, 95% CI = -17.31∼-6.16; WMD = -11.15, 95% CI = -16.64∼-5.04; WMD = -11.70, 95% CI = -16.98∼-5.60; WMD = -11.04, 95% CI = -16.97∼-5.34; WMD = -13.27, 95% CI = -19.22∼-7.40; WMD = -10.25, 95% CI = -15.66∼-4.32; and WMD = -11.60, 95% CI = -17.89∼-5.57, respectively). Treatment with ropinirole, rasagiline, rotigotine, entacapone, pramipexole, sumanirole, bromocriptine, piribedil or levodopa, with placebo as a control, on PD exhibited no significant differences on PD symptoms when the UPDRS II was used for evaluation. Moreover, using the UPDRS III, the SUCRA values indicated that a pomorphine had the best efficacy on the non-motor symptoms of PD (99.0%). Using the UPDRS II, the SUCRA values for ropinirole, rasagiline, rotigotine, entacapone, pramipexole, sumanirole, bromocriptine, piribedil and levodopa treatments, with placebo as a control, indicated that bromocriptine showed the best efficacy on the non-motor symptoms of PD (75.6%). Among ropinirole, rasagiline, rotigotine, entacapone, apomorphine, pramipexole, sumanirole, bromocriptine, piribedil and levodopa, with placebo as a control, apomorphine may be the most efficacious drug for therapy in treating the non-motor symptoms of PD. © 2018 The Author(s). Published by S. Karger AG, Basel.

Predictors of Mortality in Nondemented Patients With Parkinson Disease: Motor Symptoms Versus Nonmotor Symptoms.

PubMed

Santos-García, D; Suárez-Castro, E; Ernandez, J; Expósito-Ruiz, I; Tuñas-Gesto, C; Aneiros-Díaz, M; de Deus-Fonticoba, T; López-Fernández, M; Núñez-Arias, D

2018-01-01

The aim of this study is to identify risk factors for mortality in a community-based cohort of nondemented patients with Parkinson disease (PD) during prospective long-term follow-up, while also comparing the effect of motor complications to nonmotor symptoms (NMS) on risk of mortality. One hundred forty seven nondemented patients with PD (57.1% males; 70.9 ± 8.6 years old) were included in this 48 month follow-up, longitudinal, single, evaluation study. Motor and therapy-related complications were assessed using the Unified Parkinson's Disease Rating Scale/part-IV (UPDRS-IV). Non-Motor Symptoms Scale (NMSS) total score was used to assess NMS burden. Cox proportional hazard models were applied to identify independent predictors of mortality during follow-up. Twenty-two patients of 146 (15.1%) died (1 case without information). Both UPDRS-IV and NMSS total scores were higher at baseline in patients with PD who died (3.5 ± 3.1 vs 2.4 ± 2.4, P = .049 and 96.9 ± 58.6 vs 61.9 ± 51.0, P = .004, respectively). Unadjusted hazard ratios (HRs) associated with UPDRS-IV and NMSS total scores among those who died during follow-up were 1.171 (95% confidence interval [CI]: 1.012-1.357; P = .035) and 1.008 (95% CI: 1.002-1.013; P = .006), respectively. Independent predictors of mortality during follow-up after adjusting for other covariates were UPDRS-IV (HR: 1.224; 95% CI: 1.002-1.494; P = .047), age (HR: 1.231; 95% CI: 1104-1.374; P < .0001), and comorbidity (Charlson Index; HR: 1.429; 95% CI: 1.023-1.994; P = .036), but not NMSS total score (HR: 1.005; 95% CI: 0.996-1.014; P = .263). Both motor complications (UPDRS-IV) and NMS (NMSS) were associated with mortality at 4 years, being motor complications an independent predictor of it.

Patients' perception of Parkinson's disease-associated pain following initiation of rotigotine: a multicenter non-interventional study.

PubMed

Timmermann, Lars; Oehlwein, Christian; Ransmayr, Gerhard; Fröhlich, Holger; Will, Edgar; Schroeder, Hanna; Lauterbach, Thomas; Bauer, Lars; Kassubek, Jan

2017-01-01

To evaluate Parkinson's disease (PD)-associated pain as perceived by the patients (subjective characterization), and how this may change following initiation of rotigotine transdermal patch. SP1058 was a non-interventional study conducted in routine clinical practice in Germany and Austria in patients experiencing PD-associated pain (per the physician's assessment). Data were collected at baseline (ie, before rotigotine initiation) and at a routine visit after ≥25 days (-3 days allowed) of treatment on a maintenance dose of rotigotine (end of study [EoS]). Pain perception was assessed using the 12-item Pain Description List of the validated German Pain Questionnaire (each item ranked 0 = 'not true' to 3 = 'very true'). Primary effectiveness variable: change from baseline to EoS in the sum score of the 4 'affective dimension' items of the Pain Description List. Secondary effectiveness variables: change from baseline to EoS in Unified Parkinson's Disease Rating Scale (UPDRS) II, III, and II+III scores, and Parkinson's Disease Questionnaire (PDQ-8) total score (PD-related quality-of-life). Other variables included scores of the eight 'sensory dimension' items of the Pain Description List. Of 93 enrolled patients (mean [SD] age: 71.1 [9.0] years; male: 48 [52%]), 77 (83%) completed the study, and 70 comprised the full analysis set. The mean (SD) change from baseline in the sum score of the four 'affective dimension' items was -1.3 (2.8) indicating a numerical improvement (baseline: 3.9 [3.4]). In the 'sensory dimension', pain was mostly perceived as 'pulling' at baseline (49/70 [70%]); 'largely true'/'very true'). Numerical improvements were observed in all UPDRS scores (mean [SD] change in UPDRS II+III: -5.3 [10.5]; baseline: 36.0 [15.9]), and in PDQ-8 total score (-2.0 [4.8]; baseline: 10.7 [5.9]). Adverse drug reactions were consistent with dopaminergic stimulation and transdermal administration. The perception of the 'affective dimension' of PD-associated pain numerically improved in patients treated with rotigotine. ClinicalTrials.gov identifier: NCT01606670; https://clinicaltrials.gov/ct2/show/NCT01606670?term=NCT01606670&rank=1.

Eradication of Helicobacter pylori Infection Improves Levodopa Action, Clinical Symptoms and Quality of Life in Patients with Parkinson's Disease

PubMed Central

Hashim, Hasriza; Azmin, Shahrul; Razlan, Hamizah; Yahya, Nafisah Wan; Tan, Hui Jan; Manaf, M. Rizal Abdul; Ibrahim, Norlinah Mohamed

2014-01-01

Background Previous studies have demonstrated a higher prevalence of Helicobacter pylori (H. pylori) infection in patients with Parkinson's disease (PD) compared to controls. H. pylori infection affects levodopa absorption and its eradication significantly improves clinical response to levodopa. Here, we studied the prevalence of H. pylori infection and its eradication effects among our PD patients. Methods A prospective study involving idiopathic PD patients on levodopa therapy. 13C-urea breath test (UBT) was used to detect H. pylori. UBT-positive patients were given standard eradication therapy and followed up at 6 and 12 weeks in an open label single arm design. Repeat UBT was performed at 12 weeks. The UPDRS, PD NMQ, PD NMSS and PDQ-39 were administered at baseline and post-eradication (6 and 12 weeks). Levodopa ‘onset’ time and ON-duration were recorded. Results Of 82 patients recruited, 27 (32.9%) had positive UBT. H. pylori-positive patients had significantly poorer total UPDRS (p = 0.005) and PDQ39 (p<0.0001) scores compared to H. pylori-negative patients. At 12 weeks post-eradication, the mean levodopa onset time shortened by 14 minutes (p = 0.011). The mean ON duration time increased by 56 minutes at week 6 (p = 0.041) and 38 minutes at week 12 (p = 0.035). The total UPDRS scores (p<0.0001), scores for parts II (p = 0.001), III (p<0.0001) and IV (p = 0.009) were significantly better. The total PDQ-39 scores (p = 0.001) and subdomains mobility (p = 0.002), ADL (p = 0.001), emotional well being (p = 0.026) and stigma (p = 0.034) significantly improved. The PD NMSQ did not show significant improvement. Conclusions H. pylori eradication improved levodopa onset time, ON duration, motor severity and quality of life parameters. Screening and eradication of H. pylori is inexpensive and should be recommended in PD patients, particularly those with erratic response to levodopa. Trial Registration ClinicalTrials.gov NCT02112812 PMID:25411976

The subthalamic microlesion story in Parkinson's disease: electrode insertion-related motor improvement with relative cortico-subcortical hypoactivation in fMRI.

PubMed

Jech, Robert; Mueller, Karsten; Urgošík, Dušan; Sieger, Tomáš; Holiga, Štefan; Růžička, Filip; Dušek, Petr; Havránková, Petra; Vymazal, Josef; Růžička, Evžen

2012-01-01

Electrode implantation into the subthalamic nucleus for deep brain stimulation in Parkinson's disease (PD) is associated with a temporary motor improvement occurring prior to neurostimulation. We studied this phenomenon by functional magnetic resonance imaging (fMRI) when considering the Unified Parkinson's Disease Rating Scale (UPDRS-III) and collateral oedema. Twelve patients with PD (age 55.9± (SD)6.8 years, PD duration 9-15 years) underwent bilateral electrode implantation into the subthalamic nucleus. The fMRI was carried out after an overnight withdrawal of levodopa (OFF condition): (i) before and (ii) within three days after surgery in absence of neurostimulation. The motor task involved visually triggered finger tapping. The OFF/UPDRS-III score dropped from 33.8±8.7 before to 23.3±4.8 after the surgery (p<0.001), correlating with the postoperative oedema score (p<0.05). During the motor task, bilateral activation of the thalamus and basal ganglia, motor cortex and insula were preoperatively higher than after surgery (p<0.001). The results became more enhanced after compensation for the oedema and UPDRS-III scores. In addition, the rigidity and axial symptoms score correlated inversely with activation of the putamen and globus pallidus (p<0.0001). One month later, the OFF/UPDRS-III score had returned to the preoperative level (35.8±7.0, p = 0.4).In conclusion, motor improvement induced by insertion of an inactive electrode into the subthalamic nucleus caused an acute microlesion which was at least partially related to the collateral oedema and associated with extensive impact on the motor network. This was postoperatively manifested as lowered movement-related activation at the cortical and subcortical levels and differed from the known effects of neurostimulation or levodopa. The motor system finally adapted to the microlesion within one month as suggested by loss of motor improvement and good efficacy of deep brain stimulation.

The Subthalamic Microlesion Story in Parkinson's Disease: Electrode Insertion-Related Motor Improvement with Relative Cortico-Subcortical Hypoactivation in fMRI

PubMed Central

Urgošík, Dušan; Sieger, Tomáš; Holiga, Štefan; Růžička, Filip; Dušek, Petr; Havránková, Petra; Vymazal, Josef; Růžička, Evžen

2012-01-01

Electrode implantation into the subthalamic nucleus for deep brain stimulation in Parkinson's disease (PD) is associated with a temporary motor improvement occurring prior to neurostimulation. We studied this phenomenon by functional magnetic resonance imaging (fMRI) when considering the Unified Parkinson's Disease Rating Scale (UPDRS-III) and collateral oedema. Twelve patients with PD (age 55.9± (SD)6.8 years, PD duration 9–15 years) underwent bilateral electrode implantation into the subthalamic nucleus. The fMRI was carried out after an overnight withdrawal of levodopa (OFF condition): (i) before and (ii) within three days after surgery in absence of neurostimulation. The motor task involved visually triggered finger tapping. The OFF/UPDRS-III score dropped from 33.8±8.7 before to 23.3±4.8 after the surgery (p<0.001), correlating with the postoperative oedema score (p<0.05). During the motor task, bilateral activation of the thalamus and basal ganglia, motor cortex and insula were preoperatively higher than after surgery (p<0.001). The results became more enhanced after compensation for the oedema and UPDRS-III scores. In addition, the rigidity and axial symptoms score correlated inversely with activation of the putamen and globus pallidus (p<0.0001). One month later, the OFF/UPDRS-III score had returned to the preoperative level (35.8±7.0, p = 0.4). In conclusion, motor improvement induced by insertion of an inactive electrode into the subthalamic nucleus caused an acute microlesion which was at least partially related to the collateral oedema and associated with extensive impact on the motor network. This was postoperatively manifested as lowered movement-related activation at the cortical and subcortical levels and differed from the known effects of neurostimulation or levodopa. The motor system finally adapted to the microlesion within one month as suggested by loss of motor improvement and good efficacy of deep brain stimulation. PMID:23145068

Subthalamic Nucleus Deep Brain Stimulation in Early Stage Parkinson’s Disease

PubMed Central

Charles, David; Konrad, Peter E.; Neimat, Joseph S.; Molinari, Anna L.; Tramontana, Michael G.; Finder, Stuart G.; Gill, Chandler E.; Bliton, Mark J.; Kao, Chris C.; Phibbs, Fenna T.; Hedera, Peter; Salomon, Ronald M.; Cannard, Kevin R.; Wang, Lily; Song, Yanna; Davis, Thomas L.

2014-01-01

Background Deep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinson’s disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD. Methods Thirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50–75, on medication ≥ 6 months but < 4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n=15) or DBS+ODT (n=15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months. Results As hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. The DBS+ODT group took less medication at all time points, and this reached maximum difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS+ODT group suffered serious adverse events; remaining adverse events were mild or transient. Conclusions This study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD. PMID:24768120

Subthalamic nucleus deep brain stimulation in early stage Parkinson's disease.

PubMed

Charles, David; Konrad, Peter E; Neimat, Joseph S; Molinari, Anna L; Tramontana, Michael G; Finder, Stuart G; Gill, Chandler E; Bliton, Mark J; Kao, Chris; Phibbs, Fenna T; Hedera, Peter; Salomon, Ronald M; Cannard, Kevin R; Wang, Lily; Song, Yanna; Davis, Thomas L

2014-07-01

Deep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinson's disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD. Thirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50-75, on medication ≥6 months but ≤4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n = 15) or DBS + ODT (n = 15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months. As hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. Medication requirements in the DBS + ODT group were lower at all time points with a maximal difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS + ODT group suffered serious adverse events; remaining adverse events were mild or transient. This study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD. Copyright © 2014 Elsevier Ltd. All rights reserved.

Voice Tremor in Parkinson's Disease: An Acoustic Study.

PubMed

Gillivan-Murphy, Patricia; Miller, Nick; Carding, Paul

2018-01-30

Voice tremor associated with Parkinson disease (PD) has not been characterized. Its relationship with voice disability and disease variables is unknown. This study aimed to evaluate voice tremor in people with PD (pwPD) and a matched control group using acoustic analysis, and to examine correlations with voice disability and disease variables. Acoustic voice tremor analysis was completed on 30 pwPD and 28 age-gender matched controls. Voice disability (Voice Handicap Index), and disease variables of disease duration, Activities of Daily Living (Unified Parkinson's Disease Rating Scale [UPDRS II]), and motor symptoms related to PD (UPDRS III) were examined for relationship with voice tremor measures. Voice tremor was detected acoustically in pwPD and controls with similar frequency. PwPD had a statistically significantly higher rate of amplitude tremor (Hz) than controls (P = 0.001). Rate of amplitude tremor was negatively and significantly correlated with UPDRS III total score (rho -0.509). For pwPD, the magnitude and periodicity of acoustic tremor was higher than for controls without statistical significance. The magnitude of frequency tremor (Mftr%) was positively and significantly correlated with disease duration (rho 0.463). PwPD had higher Voice Handicap Index total, functional, emotional, and physical subscale scores than matched controls (P < 0.001). Voice disability did not correlate significantly with acoustic voice tremor measures. Acoustic analysis enhances understanding of PD voice tremor characteristics, its pathophysiology, and its relationship with voice disability and disease symptomatology. Copyright © 2018 The Voice Foundation. All rights reserved.

Outcomes from stimulation of the caudal zona incerta and pedunculopontine nucleus in patients with Parkinson's disease.

PubMed

Khan, Sadaquate; Mooney, Lucy; Plaha, Puneet; Javed, Shazia; White, Paul; Whone, Alan L; Gill, Steven S

2011-04-01

Axial symptoms including postural instability, falls and failure of gait initiation are some of the most disabling motor symptoms of Parkinson's disease (PD). We performed bilateral deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) in combination with the caudal zona incerta (cZi) in order to determine their efficacy in alleviating these symptoms. Seven patients with predominant axial symptoms in both the 'on' and 'off' medication states underwent bilateral cZi and PPN DBS. Motor outcomes were assessed using the motor component of the Unified Parkinson's Disease Rating Scale (UPDRS 3) and a composite axial subscore was derived from items 27, 28, 29 and 30 (arising from chair, posture, gait and postural stability). Quality of life was measured using the PDQ39. Comparisons were made between scores obtained at baseline and those at a mean follow-up of 12 months. In both the off and on medication states, a statistically significant improvement in the UPDRS part 3 score was achieved by stimulation of the PPN, cZi and both in combination. In the off medication state, our composite axial subscore of the UPDRS part 3 improved with stimulation of the PPN, cZi and both in combination. The composite axial subscore, in the 'on' medication state, however, only showed a statistically significant improvement when a combination of cZi and PPN stimulation was used. This study provides evidence that a combination of PPN and cZi stimulation can achieve a significant improvement in the hitherto untreatable 'on' medication axial symptoms of PD.

Bladder symptoms assessed with overactive bladder questionnaire in Parkinson's disease.

PubMed

Iacovelli, Elisa; Gilio, Francesca; Meco, Giuseppe; Fattapposta, Francesco; Vanacore, Nicola; Brusa, Livia; Giacomelli, Elena; Gabriele, Maria; Rubino, Alfonso; Locuratolo, Nicoletta; Iani, Cesare; Pichiorri, Floriana; Colosimo, Carlo; Carbone, Antonio; Palleschi, Giovanni; Inghilleri, Maurizio

2010-07-15

In Parkinson's disease (PD) the urinary dysfunction manifests primarily with symptoms of overactive bladder (OAB). The OAB questionnaire (OAB-q) is a measure designed to assess the impact of OAB symptoms on health-related quality of life. In this study, we quantified the urinary symptoms in a large cohort of PD patients by using the OAB-q short form. Possible correlations between the OAB-q and clinical features were tested. Three hundred and two PD patients were enrolled in the study. Correlations between the OAB-q and sex, age, Unified Parkinson's Disease Rating Scale part III (UPDRS-III), Hoehn-Yahr (H-Y) staging, disease duration, and treatment were analyzed. Data were compared with a large cohort of 303 age-matched healthy subjects. The OAB-q yielded significantly higher scores in PD patients than in healthy subjects. In the group of PD patients, all the variables tested were similar between men and women. Pearson's coefficient showed a significant correlation between mean age, disease duration, mean OAB-q scores, UPDRS-III scores, and H-Y staging. A multiple linear regression analysis showed that OAB-q values were significantly influenced by age and UPDRS-III. No statistical correlations were found between OAB-q scores and drug therapy or the equivalent levodopa dose, whilst the items relating to the nocturia symptoms were significantly associated with the equivalent levodopa dose. Our findings suggest that bladder dysfunction assessed by OAB-q mainly correlates with UPDRS-III scores for severity of motor impairment, possibly reflecting the known role of the decline in nigrostriatal dopaminergic function in bladder dysfunction associated with PD and patients' age. Our study also suggests that the OAB-q is a simple, easily administered test that can objectively evaluate bladder function in patients with PD.

Inter-rater variability in motor function assessment in Parkinson's disease between experts in movement disorders and nurses specialising in PD management.

PubMed

de Deus Fonticoba, T; Santos García, D; Macías Arribí, M

2017-05-23

In clinical practice, assessing patients with Parkinson's disease (PD) is a complex, time-consuming task. Our purpose is to provide a rigorous and objective evaluation of how motor function in PD patients is assessed by neurologists specialising in movement disorders, on the one hand, and by nurses specialising in PD management, on the other. We conducted an observational, cross-sectional, single-centre study of 50 patients with PD (52% men; mean age: 64.7 ± 8.7 years) who were assessed between 5 January 2016 and 20 July 2016. A neurologist and a nurse evaluated motor function in the early morning hours using the Unified Parkinson's Disease Rating Scale (UPDRS) parts III and IV and Hoehn & Yahr (H&Y) scale. Tests were administered in the same PD periods (in 48 patients during the 'off' time and in 2 patients during the 'on' time). Inter-rater variability was estimated with the intraclass correlation coefficient (ICC). Forty-nine patients (98%) were classified in the same H&Y stage by both raters. Assessment times were similar for both raters. ICC for UPDRS-IV and UPDRS-III total scores were 0.955 (P<.0001) and 0.954 (P<.0001), respectively. The greatest variability was found for UPDRS-III item 29 (gait; ICC=0.746; P<.0001) and the lowest, for item 30 (postural stability; ICC=0.918; P<.0001). Motor function assessment of PD patients by a trained nurse is equivalent to that made by an expert neurologist and takes the same time to complete. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Proposing a Parkinson's disease-specific tremor scale from the MDS-UPDRS.

PubMed

Forjaz, Maria João; Ayala, Alba; Testa, Claudia M; Bain, Peter G; Elble, Rodger; Haubenberger, Dietrich; Rodriguez-Blazquez, Carmen; Deuschl, Günther; Martinez-Martin, Pablo

2015-07-01

This article proposes an International Parkinson and Movement Disorder Society (MDS)-UPDRS tremor-based scale and describes its measurement properties, with a view to developing an improved scale for assessing tremor in Parkinson's disease (PD). This was a cross-sectional, multicenter study of 435 PD patients. Rasch analysis was performed on the 11 MDS-UPDRS tremor items. Construct validity, precision, and test-retest reliability were also analyzed. After some modifications, which included removal of an item owing to redundancy, the obtained MDS-UPDRS tremor scale showed moderate reliability, unidimensionality, absence of differential item functioning, satisfactory convergent validity with medication, and better precision than the raw sum score. However, the scale displayed a floor effect and a need for more items measuring lower levels of tremor. The MDS-UPDRS tremor scale provides linear scores that can be used to assess tremor in PD in a valid, reliable way. The scale might benefit from modifications and studies that analyze its responsiveness. © 2015 International Parkinson and Movement Disorder Society.

Symptom relief in Parkinson disease by safinamide: Biochemical and clinical evidence of efficacy beyond MAO-B inhibition.

PubMed

Stocchi, F; Vacca, L; Grassini, P; De Pandis, M F; Battaglia, G; Cattaneo, C; Fariello, R G

2006-10-10

In an open pilot study, doses of safinamide (100, 150, and 200 mg once a day, higher than previously tested) were administered to 13 parkinsonian patients along with a stable dose of dopamine (DA) agonist, causing a significant progressive improvement in motor performance as evaluated by the Unified Parkinson Disease Rating Scale (UPDRS) part III over an 8-week period (4.2 points; P < 0.001). In association with levodopa, the same doses of safinamide in another group of patients (N = 11) induced a significant decrease in motor fluctuations (UPDRS part IV, 2.1 points; P < 0.001), accompanied by a dose-proportional increase of the levodopa AUC, up to 77% from baseline. Because MAO-B was fully inhibited (95%) at all doses tested, we suggest that these biochemical and symptomatic dose-dependent effects must be related to additional mechanisms of action, such as inhibition of glutamate release, increased dopamine release, or inhibition of dopamine re-uptake. These hypotheses are under investigation and will pursue confirmation in controlled clinical trials.

[Effects of Chinese herbal medicine Bushen Huoxue Granule on quality of life of patients with Parkinson disease: a randomized, double-blinded and placebo-controlled trial].

PubMed

Li, Min; Yang, Ming-hui; Liu, Yi

2012-03-01

The main clinical symptoms of Parkinson disease (PD) are resting tremor, muscle rigidity and bradykinesia. There is currently no effective treatment for PD, and dyskinesia symptoms affect the quality of life of patients with PD. The Chinese medicine therapy used for reinforcing kidney and activating blood circulation in treatment of PD was reported to achieve good clinical effects. To study the effects of Bushen Huoxue Granule, a compound traditional Chinese herbal medicine, on the quality of life of patients with PD. A total of 120 patients were enrolled from General Hospital of the People's Liberation Army in China and divided into two groups randomly. Patients in the control group were treated with a placebo and in the treatment group with Bushen Huoxue Granule based on treating with levodopa. A double-blinded clinical trial was adopted over a 3-month treatment with a follow-up period lasting 6 months. Unified Parkinson Disease Rating Scale II (UPDRS II), questionnaire-39 (PDQ-39) and Parkinson's disease sleep scale (PDSS) were adopted to measure the quality of life at baseline, after 3 months of treatment and at a 6-month follow-up. Bushen Huoxue Granule showed a higher efficacy than the control in improving life quality of patients with PD by improving scores of UPDRS II, PDQ-39 and PDSS (P<0.05). No adverse effects were found in this trial. Bushen Huoxue Granule can markedly improve the quality of life of patients with PD.

Rotigotine Effects on Early Morning Motor Function and Sleep in Parkinson's Disease: A Double-Blind, Randomized, pLacebo-Controlled Study (RECOVER)

PubMed Central

Trenkwalder, Claudia; Kies, Bryan; Rudzinska, Monika; Fine, Jennifer; Nikl, Janos; Honczarenko, Krystyna; Dioszeghy, Peter; Hill, Dennis; Anderson, Tim; Myllyla, Vilho; Kassubek, Jan; Steiger, Malcolm; Zucconi, Marco; Tolosa, Eduardo; Poewe, Werner; Surmann, Erwin; Whitesides, John; Boroojerdi, Babak; Chaudhuri, Kallol Ray

2011-01-01

In a multinational, double-blind, placebo-controlled trial (NCT00474058), 287 subjects with Parkinson's disease (PD) and unsatisfactory early-morning motor symptom control were randomized 2:1 to receive rotigotine (2–16 mg/24 hr [n = 190]) or placebo (n = 97). Treatment was titrated to optimal dose over 1–8 weeks with subsequent dose maintenance for 4 weeks. Early-morning motor function and nocturnal sleep disturbance were assessed as coprimary efficacy endpoints using the Unified Parkinson's Disease Rating Scale (UPDRS) Part III (Motor Examination) measured in the early morning prior to any medication intake and the modified Parkinson's Disease Sleep Scale (PDSS-2) (mean change from baseline to end of maintenance [EOM], last observation carried forward). At EOM, mean UPDRS Part III score had decreased by −7.0 points with rotigotine (from a baseline of 29.6 [standard deviation (SD) 12.3] and by −3.9 points with placebo (baseline 32.0 [13.3]). Mean PDSS-2 total score had decreased by −5.9 points with rotigotine (from a baseline of 19.3 [SD 9.3]) and by −1.9 points with placebo (baseline 20.5 [10.4]). This represented a significantly greater improvement with rotigotine compared with placebo on both the UPDRS Part III (treatment difference: −3.55 [95% confidence interval (CI) −5.37, −1.73]; P = 0.0002) and PDSS-2 (treatment difference: −4.26 [95% CI −6.08, −2.45]; P < 0.0001). The most frequently reported adverse events were nausea (placebo, 9%; rotigotine, 21%), application site reactions (placebo, 4%; rotigotine, 15%), and dizziness (placebo, 6%; rotigotine 10%). Twenty-four-hour transdermal delivery of rotigotine to PD patients with early-morning motor dysfunction resulted in significant benefits in control of both motor function and nocturnal sleep disturbances. © 2010 Movement Disorder Society PMID:21322021

Deep brain stimulation for patients with Parkinson's disease: Effect on caregiver burden.

PubMed

Crespo-Burillo, J A; Rivero-Celada, D; Saenz-de Cabezón, A; Casado-Pellejero, J; Alberdi-Viñas, J; Alarcia-Alejos, R

2018-04-01

Our aim is to assess the burden on caregivers of patients with Parkinson's disease treated with deep brain stimulation (DBS) compared to those caring for patients at advanced stages and undergoing other treatments. We have also assessed the variables associated with presence of caregiver overload. We included consecutive patients with Parkinson's disease treated with DBS. Our control group included patients in advanced stages of Parkinson's disease undergoing other treatments. Patients were assessed with the following scales: UPDRS-II, UPDRS-III, UPDRS-IV, Hoehn and Yahr, Schwab & England, Barthel, PDQ-39, MoCA, Apathy Evaluation Scale, HADS, and the abbreviated QUIP. Caregiver burden was evaluated with the Zarit caregiver burden interview and their moods were assessed with the HADS scale. We included 11 patients treated with DBS and 11 with other treatments. For patients treated with DBS, we observed a better quality of life according to the PDQ-39 questionnaire (P=.028), and a lower score on the HADS anxiety subscale (P=.010). Caregiver overload was observed in 54.5% of the caregivers of patients in both groups (P=1.000); Zarit scores were similar (P=.835). Caregiver overload was associated with higher scores on the caregiver's Apathy Evaluation Scale (P=.048) and on the HADS anxiety subscale (P=.006). According to our results, treatment with DBS is not associated with lower caregiver burden. Apathy in patients and anxiety in caregivers are factors associated with the appearance of overload. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Rotigotine transdermal system as add-on to oral dopamine agonist in advanced Parkinson's disease: an open-label study.

PubMed

Kim, Jong-Min; Chung, Sun Ju; Kim, Jae Woo; Jeon, Beom Seok; Singh, Pritibha; Thierfelder, Stephan; Ikeda, Junji; Bauer, Lars

2015-02-28

Achieving optimal symptom control with minimal side effects is a major goal in clinical practice. Dual-agent dopamine receptor agonist (DA) therapy in Parkinson's disease (PD) may represent a promising approach to treatment, as the combination of different pharmacokinetic/pharmacological profiles may result in a lesser need for high dosages and, accordingly, may be well tolerated. The objective of the current study was to investigate safety and efficacy of rotigotine transdermal system as add-on to oral DA in patients with advanced PD inadequately controlled with levodopa and low-dose oral DA. PD0015 was an open-label, multinational study in patients with advanced-PD and sleep disturbance or early-morning motor impairment. Patients were titrated to optimal dose rotigotine (≤8 mg/24 h) over 1-4 weeks and maintained for 4-7 weeks (8-week treatment). Dosage of levodopa and oral DA (pramipexole ≤1.5 mg/day, ropinirole ≤6.0 mg/day) was stable. Primary variable was Clinical Global Impressions (CGI) item 4: side effects, assessing safety. Other variables included adverse events (AEs), Patient Global Impressions of Change (PGIC), Unified Parkinson's Disease Rating Scale (UPDRS) II and III, Parkinson's Disease Sleep Scale (PDSS-2), Pittsburgh Sleep Quality Index (PSQI), and "off" time. Of 90 patients who received rotigotine, 79 (88%) completed the study; 5 (6%) withdrew due to AEs. Most (83/89; 93%) had a CGI-4 score <3 indicating that rotigotine add-on therapy did not interfere with functioning; 6 (7%) experienced drug-related AEs that interfered with functioning (score ≥3). AEs occurring in ≥5% were application site pruritus (13%), dizziness (10%), orthostatic hypotension (10%), nausea (8%), dyskinesia (8%), and nasopharyngitis (6%). Numerical improvements in motor function (UPDRS III), activities of daily living (UPDRS II), sleep disturbances (PDSS-2, PSQI), and reduction in "off" time were observed. The majority (71/88; 81%) improved on PGIC. Addition of rotigotine transdermal system to low-dose oral DA in patients with advanced-PD was feasible and may be associated with clinical benefit. ClinicalTrials.gov identifier NCT01723904 . Trial registration date: November 6, 2012.

Clinical outcomes of asleep vs awake deep brain stimulation for Parkinson disease.

PubMed

Brodsky, Matthew A; Anderson, Shannon; Murchison, Charles; Seier, Mara; Wilhelm, Jennifer; Vederman, Aaron; Burchiel, Kim J

2017-11-07

To compare motor and nonmotor outcomes at 6 months of asleep deep brain stimulation (DBS) for Parkinson disease (PD) using intraoperative imaging guidance to confirm electrode placement vs awake DBS using microelectrode recording to confirm electrode placement. DBS candidates with PD referred to Oregon Health & Science University underwent asleep DBS with imaging guidance. Six-month outcomes were compared to those of patients who previously underwent awake DBS by the same surgeon and center. Assessments included an "off"-levodopa Unified Parkinson's Disease Rating Scale (UPDRS) II and III, the 39-item Parkinson's Disease Questionnaire, motor diaries, and speech fluency. Thirty participants underwent asleep DBS and 39 underwent awake DBS. No difference was observed in improvement of UPDRS III (+14.8 ± 8.9 vs +17.6 ± 12.3 points, p = 0.19) or UPDRS II (+9.3 ± 2.7 vs +7.4 ± 5.8 points, p = 0.16). Improvement in "on" time without dyskinesia was superior in asleep DBS (+6.4 ± 3.0 h/d vs +1.7 ± 1.2 h/d, p = 0.002). Quality of life scores improved in both groups (+18.8 ± 9.4 in awake, +8.9 ± 11.5 in asleep). Improvement in summary index ( p = 0.004) and subscores for cognition ( p = 0.011) and communication ( p < 0.001) were superior in asleep DBS. Speech outcomes were superior in asleep DBS, both in category (+2.77 ± 4.3 points vs -6.31 ± 9.7 points ( p = 0.0012) and phonemic fluency (+1.0 ± 8.2 points vs -5.5 ± 9.6 points, p = 0.038). Asleep DBS for PD improved motor outcomes over 6 months on par with or better than awake DBS, was superior with regard to speech fluency and quality of life, and should be an option considered for all patients who are candidates for this treatment. NCT01703598. This study provides Class III evidence that for patients with PD undergoing DBS, asleep intraoperative CT imaging-guided implantation is not significantly different from awake microelectrode recording-guided implantation in improving motor outcomes at 6 months. © 2017 American Academy of Neurology.

An 8-Week Low-Intensity Progressive Cycling Training Improves Motor Functions in Patients with Early-Stage Parkinson's Disease.

PubMed

Chang, Hsiu Chen; Lu, Chin Song; Chiou, Wei Da; Chen, Chiung Chu; Weng, Yi Hsin; Chang, Ya Ju

2018-04-01

The effects of high-intensity cycling as an adjuvant therapy for early-stage Parkinson's disease (PD) were highlighted recently. However, patients experience difficulties in maintaining these cycling training programs. The present study investigated the efficacy of cycling at a mild-to-moderate intensity in early-stage PD. Thirteen PD patients were enrolled for 16 serial cycling sessions over a 2-month period. Motor function was assessed using the Unified Parkinson's Disease Rating Scale part III (UPDRS III) and Timed Up and Go (TUG) test as primary outcomes. The Montreal Cognitive Assessment (MoCA), modified Hoehn and Yahr Stage (mHYS), total UPDRS, Falls Efficacy Scale, New Freezing of Gait Questionnaire, Schwab and England Activities of Daily Living, 39-item Parkinson's Disease Questionnaire, Patient Global Impression of Change, and gait performance were assessed as secondary outcomes. The age and the age at onset were 59.67±7.24 and 53.23±10.26 years (mean±SD), respectively. The cycling cadence was 53.27±8.92 revolutions per minute. The UPDRS III score improved significantly after 8 training sessions (p=0.011) and 16 training sessions (T2) (p=0.001) in the off-state, and at T2 (p=0.004) in the on-state compared to pretraining (T0). The TUG duration was significantly shorter at T2 than at T0 (p<0.05). The findings of MoCA, total UPDRS, double limb support time, and mHYS (in both the off- and on-states) also improved significantly at T2. Our pioneer study has demonstrated that a low-intensity progressive cycling exercise can improve motor function in PD, especially akinesia. The beneficial effects were similar to those of high-intensity rehabilitation programs. Copyright © 2018 Korean Neurological Association.

Multiple balance tests improve the assessment of postural stability in subjects with Parkinson's disease

PubMed Central

Jacobs, J V; Horak, F B; Tran, V K; Nutt, J G

2006-01-01

Objectives Clinicians often base the implementation of therapies on the presence of postural instability in subjects with Parkinson's disease (PD). These decisions are frequently based on the pull test from the Unified Parkinson's Disease Rating Scale (UPDRS). We sought to determine whether combining the pull test, the one‐leg stance test, the functional reach test, and UPDRS items 27–29 (arise from chair, posture, and gait) predicts balance confidence and falling better than any test alone. Methods The study included 67 subjects with PD. Subjects performed the one‐leg stance test, the functional reach test, and the UPDRS motor exam. Subjects also responded to the Activities‐specific Balance Confidence (ABC) scale and reported how many times they fell during the previous year. Regression models determined the combination of tests that optimally predicted mean ABC scores or categorised fall frequency. Results When all tests were included in a stepwise linear regression, only gait (UPDRS item 29), the pull test (UPDRS item 30), and the one‐leg stance test, in combination, represented significant predictor variables for mean ABC scores (r2 = 0.51). A multinomial logistic regression model including the one‐leg stance test and gait represented the model with the fewest significant predictor variables that correctly identified the most subjects as fallers or non‐fallers (85% of subjects were correctly identified). Conclusions Multiple balance tests (including the one‐leg stance test, and the gait and pull test items of the UPDRS) that assess different types of postural stress provide an optimal assessment of postural stability in subjects with PD. PMID:16484639

Effects of deep brain stimulation on rest tremor progression in early stage Parkinson disease.

PubMed

Hacker, Mallory L; DeLong, Mahlon R; Turchan, Maxim; Heusinkveld, Lauren E; Ostrem, Jill L; Molinari, Anna L; Currie, Amanda D; Konrad, Peter E; Davis, Thomas L; Phibbs, Fenna T; Hedera, Peter; Cannard, Kevin R; Drye, Lea T; Sternberg, Alice L; Shade, David M; Tonascia, James; Charles, David

2018-06-29

To evaluate whether the progression of individual motor features was influenced by early deep brain stimulation (DBS), a post hoc analysis of Unified Parkinson's Disease Rating Scale-III (UPDRS-III) score (after a 7-day washout) was conducted from the 2-year DBS in early Parkinson disease (PD) pilot trial dataset. The prospective pilot trial enrolled patients with PD aged 50-75 years, treated with PD medications for 6 months-4 years, and no history of dyskinesia or other motor fluctuations, who were randomized to receive optimal drug therapy (ODT) or DBS plus ODT (DBS + ODT). At baseline and 6, 12, 18, and 24 months, all patients stopped all PD therapy for 1 week (medication and stimulation, if applicable). UPDRS-III "off" item scores were compared between the ODT and DBS + ODT groups (n = 28); items with significant between-group differences were analyzed further. UPDRS-III "off" rest tremor score change from baseline to 24 months was worse in patients receiving ODT vs DBS + ODT ( p = 0.002). Rest tremor slopes from baseline to 24 months favored DBS + ODT both "off" and "on" therapy ( p < 0.001, p = 0.003, respectively). More ODT patients developed new rest tremor in previously unaffected limbs than those receiving DBS + ODT ( p = 0.001). These results suggest the possibility that DBS in early PD may slow rest tremor progression. Future investigation in a larger cohort is needed, and these findings will be tested in the Food and Drug Administration-approved, phase III, pivotal, multicenter clinical trial evaluating DBS in early PD. This study provides Class II evidence that for patients with early PD, DBS may slow the progression of rest tremor. © 2018 American Academy of Neurology.

Validation of the Korean Version of the Scales for Outcomes in Parkinson's Disease-Sleep

PubMed Central

2017-01-01

Background Sleep problems commonly occur in patients with Parkinson's disease (PD), and are associated with a lower quality of life. The aim of the current study was to translate the English version of the Scales for Outcomes in Parkinson's Disease-Sleep (SCOPA-S) into the Korean version of SCOPA-S (K-SCOPA-S), and to evaluate its reliability and validity for use by Korean-speaking patients with PD. Methods In total, 136 patients with PD from 27 movement disorder centres of university-affiliated hospitals in Korea were enrolled in this study. They were assessed using SCOPA, Hoehn and Yahr Scale (HYS), Unified Parkinson's Disease Rating Scale (UPDRS), Parkinson's Disease Sleep Scale 2nd version (PDSS-2), Non-motor Symptoms Scale (NMSS), Montgomery Asberg Depression Scale (MADS), 39-item Parkinson's Disease Questionnaire (PDQ39), Neurogenic Orthostatic Hypotension Questionnaire (NOHQ), and Rapid Eye Movement Sleep Behaviour Disorder Questionnaire (RBDQ). The test-retest reliability was assessed over a time interval of 10–14 days. Results The internal consistency (Cronbach's α-coefficients) of K-SCOPA-S was 0.88 for nighttime sleep (NS) and 0.75 for daytime sleepiness (DS). Test-retest reliability was 0.88 and 0.85 for the NS and DS, respectively. There was a moderate correlation between the NS sub-score and PDSS-2 total score. The NS and DS sub-scores of K-SCOPA-S were correlated with motor scale such as HYS, and non-motor scales such as UPDRS I, UPDRS II, MADS, NMSS, PDQ39, and NOHQ while the DS sub-score was with RBDQ. Conclusion The K-SCOPA-S exhibited good reliability and validity for the assessment of sleep problems in the Korean patients with PD. PMID:29215823

Validation of the Korean Version of the Scales for Outcomes in Parkinson's Disease-Sleep.

PubMed

Sung, Young Hee; Kim, Hee Jin; Koh, Seong Beom; Kim, Joong Seok; Kim, Sang Jin; Cheon, Sang Myung; Cho, Jin Whan; Kim, Yoon Joong; Ma, Hyeo Il; Park, Mee Young; Baik, Jong Sam; Lee, Phil Hyu; Chung, Sun Ju; Kim, Jong Min; Song, In Uk; Kim, Han Joon; Kim, Ji Young; Kwon, Do Young; Lee, Jae Hyeok; Lee, Jee Young; Kim, Ji Seon; Yun, Ji Young; Hong, Jin Yong; Kim, Mi Jung; Youn, Jinyoung; Kim, Ji Sun; Oh, Eung Seok; Yang, Hui Jun; Yoon, Won Tae; You, Sooyeoun; Kwon, Kyum Yil; Park, Hyung Eun; Lee, Su Yun; Kim, Younsoo; Kim, Hee Tae; Ahn, Tae Beom

2018-01-08

Sleep problems commonly occur in patients with Parkinson's disease (PD), and are associated with a lower quality of life. The aim of the current study was to translate the English version of the Scales for Outcomes in Parkinson's Disease-Sleep (SCOPA-S) into the Korean version of SCOPA-S (K-SCOPA-S), and to evaluate its reliability and validity for use by Korean-speaking patients with PD. In total, 136 patients with PD from 27 movement disorder centres of university-affiliated hospitals in Korea were enrolled in this study. They were assessed using SCOPA, Hoehn and Yahr Scale (HYS), Unified Parkinson's Disease Rating Scale (UPDRS), Parkinson's Disease Sleep Scale 2nd version (PDSS-2), Non-motor Symptoms Scale (NMSS), Montgomery Asberg Depression Scale (MADS), 39-item Parkinson's Disease Questionnaire (PDQ39), Neurogenic Orthostatic Hypotension Questionnaire (NOHQ), and Rapid Eye Movement Sleep Behaviour Disorder Questionnaire (RBDQ). The test-retest reliability was assessed over a time interval of 10-14 days. The internal consistency (Cronbach's α-coefficients) of K-SCOPA-S was 0.88 for nighttime sleep (NS) and 0.75 for daytime sleepiness (DS). Test-retest reliability was 0.88 and 0.85 for the NS and DS, respectively. There was a moderate correlation between the NS sub-score and PDSS-2 total score. The NS and DS sub-scores of K-SCOPA-S were correlated with motor scale such as HYS, and non-motor scales such as UPDRS I, UPDRS II, MADS, NMSS, PDQ39, and NOHQ while the DS sub-score was with RBDQ. The K-SCOPA-S exhibited good reliability and validity for the assessment of sleep problems in the Korean patients with PD. © 2018 The Korean Academy of Medical Sciences.

Dose-dependent progression of parkinsonism in manganese-exposed welders

PubMed Central

Searles Nielsen, Susan; Criswell, Susan R.; Sheppard, Lianne; Seixas, Noah; Warden, Mark N.; Checkoway, Harvey

2017-01-01

Objective: To determine whether the parkinsonian phenotype prevalent in welders is progressive, and whether progression is related to degree of exposure to manganese (Mn)-containing welding fume. Methods: This was a trade union–based longitudinal cohort study of 886 American welding-exposed workers with 1,492 examinations by a movement disorders specialist, including 398 workers with 606 follow-up examinations up to 9.9 years after baseline. We performed linear mixed model regression with cumulative Mn exposure as the independent variable and annual change in Unified Parkinson Disease Rating Scale motor subsection part 3 (UPDRS3) as the primary outcome, and subcategories of the UPDRS3 as secondary outcomes. The primary exposure metric was cumulative Mn exposure in mg Mn/m3-year estimated from detailed work histories. Results: Progression of parkinsonism increased with cumulative Mn exposure. Specifically, we observed an annual change in UPDRS3 of 0.24 (95% confidence interval 0.10–0.38) for each mg Mn/m3-year of exposure. Exposure was most strongly associated with progression of upper limb bradykinesia, upper and lower limb rigidity, and impairment of speech and facial expression. The association between welding exposure and progression appeared particularly marked in welders who did flux core arc welding in a confined space or workers whose baseline examination was within 5 years of first welding exposure. Conclusions: Exposure to Mn-containing welding fume may cause a dose-dependent progression of parkinsonism, especially upper limb bradykinesia, limb rigidity, and impairment of speech and facial expression. PMID:28031394

Assessment of voice and speech symptoms in early Parkinson's disease by the Robertson dysarthria profile.

PubMed

Defazio, Giovanni; Guerrieri, Marta; Liuzzi, Daniele; Gigante, Angelo Fabio; di Nicola, Vincenzo

2016-03-01

Changes in voice and speech are thought to involve 75-90% of people with PD, but the impact of PD progression on voice/speech parameters is not well defined. In this study, we assessed voice/speech symptoms in 48 parkinsonian patients staging <3 on the modified Hoehn and Yahr scale and 37 healthy subjects using the Robertson dysarthria profile (a clinical-perceptual method exploring all components potentially involved in speech difficulties), the Voice handicap index (a validated measure of the impact of voice symptoms on quality of life) and the speech evaluation parameter contained in the Unified Parkinson's Disease Rating Scale part III (UPDRS-III). Accuracy and metric properties of the Robertson dysarthria profile were also measured. On Robertson dysarthria profile, all parkinsonian patients yielded lower scores than healthy control subjects. Differently, the Voice Handicap Index and the speech evaluation parameter contained in the UPDRS-III could detect speech/voice disturbances in 10 and 75% of PD patients, respectively. Validation procedure in Parkinson's disease patients showed that the Robertson dysarthria profile has acceptable reliability, satisfactory internal consistency and scaling assumptions, lack of floor and ceiling effects, and partial correlations with UPDRS-III and Voice Handicap Index. We concluded that speech/voice disturbances are widely identified by the Robertson dysarthria profile in early parkinsonian patients, even when the disturbances do not carry a significant level of disability. Robertson dysarthria profile may be a valuable tool to detect speech/voice disturbances in Parkinson's disease.

The frequency of buccopalpebral reflex in Parkinson disease.

PubMed

Eser, Hülya; Ünal, Yasemin; Kutlu, Gülnihal; Öcal, Ruhsen; İnan, Levent Ertuğrul

2016-11-17

This study aimed to define the frequency of a primitive reflex, the buccopalpebral reflex (BPR), and its association with the clinical situation in patients with Parkinson disease. Between May 2010 and May 2011, 222 patients, 115 with Parkinson disease and 107 patients without any sign of neurodegenerative disease, were included in the study. All included patients were examined for BPR and snout reflex and were also evaluated with the Mini Mental State Examination. All patients with Parkinson disease were classified with the Unified Parkinson's Disease Rating Scale (UPDRS) and the Hoehn and Yahr Score to determine their clinical severity. Sixteen patients with Parkinson disease (13.9%) had a BPR (+) and 4 patients in the control group (3.7%) (P < 0.001). The UPDRS score, UPDRS daily life activities score, and UPDRS motor system score were all higher in the group with BPR (+). All patients with a BPR also had a positive snout reflex. BPR is more frequent in patients with Parkinson disease than in patients without a neurodegenerative disease.

Efficacy and safety of adjunctive rasagiline in Japanese Parkinson's disease patients with wearing-off phenomena: A phase 2/3, randomized, double-blind, placebo-controlled, multicenter study.

PubMed

Hattori, Nobutaka; Takeda, Atsushi; Takeda, Shinichi; Nishimura, Akira; Kato, Masafumi; Mochizuki, Hideki; Nagai, Masahiro; Takahashi, Ryosuke

2018-04-27

Rasagiline, a selective, irreversible monoamine oxidase-B inhibitor, is in development in Japan as adjunctive therapy to levodopa. This Phase 2/3 trial evaluated the efficacy and safety of adjunctive rasagiline in Japanese patients with Parkinson's disease (PD) and wearing-off phenomena. Patients aged 30-79 years with diagnosed PD and stable levodopa use were randomized 1:1:1 to rasagiline (0.5/1 mg/day) or placebo for 26 weeks. The primary endpoint was change from baseline in mean daily OFF-time during the treatment period. In total, 141, 134, and 129 patients were randomized to placebo, rasagiline 0.5 mg, or rasagiline 1 mg, respectively. Baseline characteristics were well balanced. Least squares (LS) mean differences vs. placebo for change from baseline in mean daily OFF-time were -0.84 h (rasagiline 1 mg/day) and -0.60 h (rasagiline 0.5 mg/day); both differences were statistically significant. LS mean differences vs. placebo for change from baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II and Part III total scores (in ON-state) and Parkinson's Disease Questionnaire-39 Summary Index Score were: -1.27, -1.74, and -2.51 (0.5 mg/day) and -1.27, -2.14, and -3.84 (1 mg/day); all statistically significant. Treatment-emergent adverse events (TEAEs) occurred in 50.4/69.9/73.6% of the placebo, 0.5 mg/day, and 1 mg/day groups, respectively (most common TEAEs were nasopharyngitis [9.2/18.0/14.7%] and dyskinesia [7.1/8.3/16.3%]). As an adjunct to levodopa, rasagiline reduced OFF-time and improved PD symptoms/signs (MDS-UPDRS scores) and quality of life in Japanese patients with PD and wearing-off phenomena. No important safety concerns were raised. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Movement disorder symptoms associated with Unified ...

EPA Pesticide Factsheets

Objectives: The UPDRS is a commonly used neurological measurement to assess the presence and severity of parkinsonian symptoms. It has also been used to assess symptoms associated with Mn exposure. Objectives: to determine 1) if movement disorder symptoms were associated with UPDRS: Activities of Daily Living (ADL) and Motor abnormalities; and 2) which symptoms were most related to increased abnormalities on these UPDRS subscales. Participants & Methods: Correlations between self-reported movement disorder symptoms from a health questionnaire and scores obtained on UPDRS: ADL and Motor subscales, and the Bradykinesia domain of the Motor subscale, were assessed during a medical examination among 185 Mn-exposed participants from two Ohio towns. Partial correlations were used for statistical analyses, controlling for age, sex, education and a history of musculoskeletal disease.Results: The presence of movement disorder symptoms was positively associated with ADL (pr =0.647, p = <0.001), Motor (pr =0.449, p = <0.001), and Bradykinesia (pr =0.418, p = <0.001) domains on the UPDRS. Specific movement disorder symptoms most strongly associated with increased ADL and Motor scores included having difficulty getting out of chairs (pr =0.458, p = <0.001), writing (pr =0.481, p = <0.001), skilled movements (pr =0.478, p = <0.001), loss of coordination/balance (pr =0.457, p = <0.001), changes in walking (pr =0.412, p = <0.001) and slowness of movement (pr =0.539, p = <0.0

Inducible nitric oxide synthase gene methylation and parkinsonism in manganese-exposed welders

PubMed Central

Nielsen, Susan Searles; Checkoway, Harvey; Criswell, Susan R.; Farin, Federico M.; Stapleton, Patricia L.; Sheppard, Lianne; Racette, Brad A.

2015-01-01

Introduction Neurologist-assessed parkinsonism signs are prevalent among workers exposed to manganese (Mn)-containing welding fume. Neuroinflammation may possibly play a role. Inducible nitric oxide synthase, coded by NOS2, is involved in inflammation, and particulate exposure increases the gene’s expression through methylation of CpG sites in the 5′ region. Methods We assessed DNA methylation at three CpG sites in the NOS2 exon 1 from blood from 201 welders. All were non-Hispanic Caucasian men 25–65 years old who were examined by a neurologist specializing in movement disorders. We categorized the workers according to their Unified Parkinson Disease Rating Scale motor subsection 3 (UPDRS3) scores as parkinsonism cases (UPDRS3 ≥ 15; n = 49), controls (UPDRS3 < 6; n = 103), or intermediate (UPDRS3 ≥6 to <15; n = 49). Results While accounting for age, examiner and experimental plate, parkinsonism cases had lower mean NOS2 methylation than controls (p-value for trend = 0.04), specifically at CpG site 8329 located in an exonic splicing enhancer of NOS2 (p-value for trend = 0.07). These associations were not observed for the intermediate UPDRS3 group (both p-value for trend ≥ 0.59). Conclusions Inflammation mediated by inducible nitric oxide synthase may possibly contribute to the association between welding fume and parkinsonism, but requires verification in a longitudinal study. PMID:25634431

A randomized clinical trial of high-dosage coenzyme Q10 in early Parkinson disease: no evidence of benefit.

PubMed

Beal, M Flint; Oakes, David; Shoulson, Ira; Henchcliffe, Claire; Galpern, Wendy R; Haas, Richard; Juncos, Jorge L; Nutt, John G; Voss, Tiffini Smith; Ravina, Bernard; Shults, Clifford M; Helles, Karen; Snively, Victoria; Lew, Mark F; Griebner, Brian; Watts, Arthur; Gao, Shan; Pourcher, Emmanuelle; Bond, Louisette; Kompoliti, Katie; Agarwal, Pinky; Sia, Cherissa; Jog, Mandar; Cole, Linda; Sultana, Munira; Kurlan, Roger; Richard, Irene; Deeley, Cheryl; Waters, Cheryl H; Figueroa, Angel; Arkun, Ani; Brodsky, Matthew; Ondo, William G; Hunter, Christine B; Jimenez-Shahed, Joohi; Palao, Alicia; Miyasaki, Janis M; So, Julie; Tetrud, James; Reys, Liza; Smith, Katharine; Singer, Carlos; Blenke, Anita; Russell, David S; Cotto, Candace; Friedman, Joseph H; Lannon, Margaret; Zhang, Lin; Drasby, Edward; Kumar, Rajeev; Subramanian, Thyagarajan; Ford, Donna Stuppy; Grimes, David A; Cote, Diane; Conway, Jennifer; Siderowf, Andrew D; Evatt, Marian Leslie; Sommerfeld, Barbara; Lieberman, Abraham N; Okun, Michael S; Rodriguez, Ramon L; Merritt, Stacy; Swartz, Camille Louise; Martin, W R Wayne; King, Pamela; Stover, Natividad; Guthrie, Stephanie; Watts, Ray L; Ahmed, Anwar; Fernandez, Hubert H; Winters, Adrienna; Mari, Zoltan; Dawson, Ted M; Dunlop, Becky; Feigin, Andrew S; Shannon, Barbara; Nirenberg, Melissa Jill; Ogg, Mattson; Ellias, Samuel A; Thomas, Cathi-Ann; Frei, Karen; Bodis-Wollner, Ivan; Glazman, Sofya; Mayer, Thomas; Hauser, Robert A; Pahwa, Rajesh; Langhammer, April; Ranawaya, Ranjit; Derwent, Lorelei; Sethi, Kapil D; Farrow, Buff; Prakash, Rajan; Litvan, Irene; Robinson, Annette; Sahay, Alok; Gartner, Maureen; Hinson, Vanessa K; Markind, Samuel; Pelikan, Melisa; Perlmutter, Joel S; Hartlein, Johanna; Molho, Eric; Evans, Sharon; Adler, Charles H; Duffy, Amy; Lind, Marlene; Elmer, Lawrence; Davis, Kathy; Spears, Julia; Wilson, Stephanie; Leehey, Maureen A; Hermanowicz, Neal; Niswonger, Shari; Shill, Holly A; Obradov, Sanja; Rajput, Alex; Cowper, Marilyn; Lessig, Stephanie; Song, David; Fontaine, Deborah; Zadikoff, Cindy; Williams, Karen; Blindauer, Karen A; Bergholte, Jo; Propsom, Clara Schindler; Stacy, Mark A; Field, Joanne; Mihaila, Dragos; Chilton, Mark; Uc, Ergun Y; Sieren, Jeri; Simon, David K; Kraics, Lauren; Silver, Althea; Boyd, James T; Hamill, Robert W; Ingvoldstad, Christopher; Young, Jennifer; Thomas, Karen; Kostyk, Sandra K; Wojcieszek, Joanne; Pfeiffer, Ronald F; Panisset, Michel; Beland, Monica; Reich, Stephen G; Cines, Michelle; Zappala, Nancy; Rivest, Jean; Zweig, Richard; Lumina, L Pepper; Hilliard, Colette Lynn; Grill, Stephen; Kellermann, Marye; Tuite, Paul; Rolandelli, Susan; Kang, Un Jung; Young, Joan; Rao, Jayaraman; Cook, Maureen M; Severt, Lawrence; Boyar, Karyn

2014-05-01

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

A Randomized Controlled Trial of Chinese Medicine on Nonmotor Symptoms in Parkinson's Disease

PubMed Central

Chua, Ka-Kit; Wong, Adrian; Lau, Yin-Kei; Bian, Zhao-Xiang; Lu, Jia-Hong; Liu, Liang-Feng; Chen, Lei-Lei; Chan, Ka-Ho; Tse, Kim-Pong; Chan, Anne; Wu, Justin; Zhu, Li-Xing

2017-01-01

Nonmotor symptoms (NMS) of Parkinson's disease (PD) have devastating impacts on both patients and their caregivers. Jiawei-Liujunzi Tang (JLT) has been used to treat some NMS of PD based on the Chinese medicine theory since Qing dynasty. Here we report a double-blind, randomized, placebo-controlled, add-on clinical trial aiming at evaluating the efficacy and safety of the JLT in treating NMS in PD patients. We randomly assigned 111 patients with idiopathic PD to receive either JLT or placebo for 32 weeks. Outcome measures were baseline to week 32 changes in Movement Disorder Society-Sponsored Revision of Unified PD Rating Scale (MDS-UPDRS) Parts I–IV and in NMS assessment scale for PD (NMSS). We observed improvements in the NMSS total score (p = 0.019), mood/cognition (p = 0.005), and reduction in hallucinations (p = 0.024). In addition, post hoc analysis showed a significant reduction in constipation (p < 0.001). However, there was no evidence of improvement in MDS-UPDRS Part I total score (p = 0.216) at week 32. Adverse events (AEs) were mild and comparable between the two groups. In conclusion, long-term administration of JLT is well tolerated and shows significant benefits in improving NMS including mood, cognition, and constipation. PMID:28630780

Movement disorder symptoms associated with Unified Parkinson’s Disease Rating Scale (UPDRS) in two manganese (Mn)-exposed communities

EPA Science Inventory

Objectives: The UPDRS is a commonly used neurological measurement to assess the presence and severity of parkinsonian symptoms. It has also been used to assess symptoms associated with Mn exposure. Objectives: to determine 1) if movement disorder symptoms were associated with UP...

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

PubMed

Hauser, Robert A; Auinger, Peggy

2011-04-01

Two common primary efficacy outcome measures in Parkinson's disease (PD) are change in Unified Parkinson's Disease Rating Scale (UPDRS) scores in early PD and change in "off" time in patients with motor fluctuations. Defining the minimal clinically important change (MCIC) in these outcome measures is important to interpret the clinical relevance of changes observed in clinical trials and other situations. We analyzed data from 2 multicenter, placebo-controlled, randomized clinical trials of rasagiline; TEMPO studied 404 early PD subjects, and PRESTO studied 472 levodopa-treated subjects with motor fluctuations. An anchor-based approach using clinical global impression of improvement (CGI-I) was used to determine MCIC for UPDRS scores and daily "off" time. MCIC was defined as mean change in actively treated subjects rated minimally improved on CGI-I. Receiver operating characteristic (ROC) curves defined optimal cutoffs discriminating between changed and unchanged subjects. MCIC for improvement in total UPDRS score (parts I-III) in early PD was determined to be -3.5 points based on mean scores and -3.0 points based on ROC curves. In addition, we found an MCIC for reduction in "off" time of 1.0 hours as defined by mean reduction in "off" time in active treated subjects self-rated as minimally improved on CGI-I minus mean reduction in "off" time in placebo-treated subjects self-rated as unchanged (1.9-0.9 hours). We hypothesize that many methodological factors can influence determination of the MCIC, and a range of values is likely to emerge from multiple studies. Copyright © 2011 Movement Disorder Society.

Orodispersible sublingual piribedil to abort OFF episodes: a single dose placebo-controlled, randomized, double-blind, cross-over study.

PubMed

Rascol, Olivier; Azulay, Jean-Philippe; Blin, Olivier; Bonnet, Anne-Marie; Brefel-Courbon, Christine; Césaro, Pierre; Damier, Philippe; Debilly, Bérengère; Durif, Frank; Galitzky, Monique; Grouin, Jean-Marie; Pennaforte, Sylvie; Villafane, Gabriel; Yaici, Sadek; Agid, Yves

2010-02-15

S90049, a novel sublingual formulation of the non-ergoline D(2)-D(3) 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 x 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 (Delta UPDRS 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 was superior to placebo on Delta UPDRS 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, Delta UPDRS 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. (c) 2009 Movement Disorder Society.

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

PubMed

Hauser, Robert A; Silver, Dee; Choudhry, Azhar; Eyal, Eli; Isaacson, Stuart

2014-07-01

Dopamine agonists (DA) are often used as first-line monotherapy for the symptomatic control of Parkinson's disease (PD). However, DA monotherapy typically becomes inadequate within a few years, at which time the DA dosage must be increased or other antiparkinsonian medications added. Adding a monoamine oxidase-B (MAO-B) inhibitor to DA monotherapy might improve symptomatic control while maintaining good safety and tolerability. We conducted an 18-week, randomized, double-blind, placebo-controlled trial of rasagiline 1 mg/d as an add-on to DA therapy (ropinirole ≥ 6 mg/d or pramipexole ≥ 1.0 mg/d) in early PD patients whose conditions were not adequately controlled on their current treatment regimen. The primary efficacy variable was the change in total Unified Parkinson Disease Rating Scale (UPDRS) score (sum of parts I, II, and III) from baseline to week 18, comparing rasagiline and placebo groups. The modified intent-to-treat (ITT) population included 321 subjects whose mean ± SD age was 62.6 ± 9.7, and duration of PD was 2.1 ± 2.1 years. Results demonstrated a significantly greater improvement in total UPDRS scores from baseline to week 18 in the rasagiline group compared with the placebo group (least squares [LS] mean difference ± SE, -2.4 ± 0.95; 95% confidence interval [CI], -4.3, -0.5; P = 0.012). Mean improvement (LS mean ± SE) was -3.6 ± 0.68 in the rasagiline group and -1.2 ± 0.68 in the placebo group. Rasagiline was well tolerated, and the most common adverse events (AEs; rasagiline vs. placebo) were dizziness (7.4% vs. 6.1%), somnolence (6.8% vs. 6.7%), and headache (6.2% vs. 4.3%). Rasagiline 1 mg/d provided statistically significant improvement when added to dopamine agonist therapy and was well tolerated. © 2014 International Parkinson and Movement Disorder Society.

What increases the risk of malnutrition in Parkinson's disease?

PubMed

Tomic, Svetlana; Pekic, Vlasta; Popijac, Zeljka; Pucic, Tomislav; Petek, Marta; Kuric, Tihana Gilman; Misevic, Sanja; Kramaric, Ruzica Palic

2017-04-15

Parkinson's disease (PD) patients are at a higher risk of malnutrition. The prevalence has been estimated to 0-24%, while 3%-60% of PD patients are reported to be at risk of malnutrition. To date, there is no clear explanation for malnutrition in these patients. The aim of this study was to determine the prevalence of malnutrition and to analyze factors that influence its appearance. The Mini Nutritional Assessment (MNA) was used to determine normal nutritional status; at risk of malnutrition; and already malnourished status. The Unified Parkinson's Disease Rating Scale (UPDRS) parts III and IV, Hoehn and Yahr scale (H&Y scale), Beck Depression Inventory (BDI), Mini Mental State Examination (MMSE), Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale - eating part (QUIP-RS) and Mini Nutritional Assessment (MNA) were used to evaluate the factors affecting patient nutritional status. Out of 96 patients, 55,2% were at risk of malnutrition, while 8,3% had already been malnourished. Age, H&Y scale, UPDRS part III, 'off' periods and depression influence negatively on MNA. More patients with 'off' periods were rigor dominant. Thyroid gland hormone therapy was related to malnutrition, while patients with normal nutritional status used ropinirole more often than pramipexole. Factors affecting nutritional status are age, motor symptoms and stage severity, 'off' states, rigidity dominant type with 'off' states, and thyroid hormone replacement therapy. Ropinirole exhibited the possible 'protective' effect against malnutrition. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of cannabidiol in the treatment of patients with Parkinson's disease: an exploratory double-blind trial.

PubMed

Chagas, Marcos Hortes N; Zuardi, Antonio W; Tumas, Vitor; Pena-Pereira, Márcio Alexandre; Sobreira, Emmanuelle T; Bergamaschi, Mateus M; dos Santos, Antonio Carlos; Teixeira, Antonio Lucio; Hallak, Jaime E C; Crippa, José Alexandre S

2014-11-01

Parkinson's disease (PD) has a progressive course and is characterized by the degeneration of dopaminergic neurons. Although no neuroprotective treatments for PD have been found to date, the endocannabinoid system has emerged as a promising target. From a sample of 119 patients consecutively evaluated in a specialized movement disorders outpatient clinic, we selected 21 PD patients without dementia or comorbid psychiatric conditions. Participants were assigned to three groups of seven subjects each who were treated with placebo, cannabidiol (CBD) 75 mg/day or CBD 300 mg/day. One week before the trial and in the last week of treatment participants were assessed in respect to (i) motor and general symptoms score (UPDRS); (ii) well-being and quality of life (PDQ-39); and (iii) possible neuroprotective effects (BDNF and H(1)-MRS). We found no statistically significant differences in UPDRS scores, plasma BDNF levels or H(1)-MRS measures. However, the groups treated with placebo and CBD 300 mg/day had significantly different mean total scores in the PDQ-39 (p = 0.05). Our findings point to a possible effect of CBD in improving quality of life measures in PD patients with no psychiatric comorbidities; however, studies with larger samples and specific objectives are required before definitive conclusions can be drawn. © The Author(s) 2014.

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

PubMed

Hauser, Robert A; Abler, Victor; Eyal, Eli; Eliaz, Rom E

2016-10-01

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

Impact of motor fluctuations on real-life gait in Parkinson's patients.

PubMed

Silva de Lima, Ana Lígia; Evers, Luc J W; Hahn, Tim; de Vries, Nienke M; Daeschler, Margaret; Boroojerdi, Babak; Terricabras, Dolors; Little, Max A; Bloem, Bastiaan R; Faber, Marjan J

2018-05-01

People with PD (PWP) have an increased risk of becoming inactive. Wearable sensors can provide insights into daily physical activity and walking patterns. (1) Is the severity of motor fluctuations associated with sensor-derived average daily walking quantity? (2) Is the severity of motor fluctuations associated with the amount of change in sensor-derived walking quantity after levodopa intake? 304 Dutch PWP from the Parkinson@Home study were included. At baseline, all participants received a clinical examination. During the follow-up period (median: 97 days; 25-Interquartile range-IQR: 91 days, 75-IQR: 188 days), participants used the Fox Wearable Companion app and streamed smartwatch accelerometer data to a cloud platform. The first research question was assessed by linear regression on the sensor-derived mean time spent walking/day with the severity of fluctuations (MDS-UPDRS item 4.4) as independent variable, controlled for age and MDS-UPDRS part-III score. The second research question was assessed by linear regression on the sensor-derived mean post-levodopa walking quantity, with the sensor-derived mean pre-levodopa walking quantity and severity of fluctuations as independent variables, controlled for mean time spent walking per day, age and MDS-UPDRS part-III score. PWP spent most time walking between 8am and 1pm, summing up to 72 ± 39 (mean ± standard deviation) minutes of walking/day. The severity of motor fluctuations did not influence the mean time spent walking (B = 2.4 ± 1.9, p = 0.20), but higher age (B = -1.3 ± 0.3, p = < 0.001) and greater severity of motor symptoms (B = -0.6 ± 0.2, p < 0.001) was associated with less time spent walking (F(3216) = 14.6, p < .001, R 2  = .17). The severity of fluctuations was not associated with the amount of change in time spent walking in relation to levodopa intake in any part of the day. Analysis of sensor-derived gait quantity suggests that the severity of motor fluctuations is not associated with changes in real-life walking patterns in mildly to moderate affected PWP. Copyright © 2018 Elsevier B.V. All rights reserved.

Association Between Change in Body Mass Index, Unified Parkinson’s Disease Rating Scale Scores, and Survival Among Persons With Parkinson Disease

PubMed Central

Wills, Anne-Marie A.; Pérez, Adriana; Wang, Jue; Su, Xiao; Morgan, John; Rajan, Suja S.; Leehey, Maureen A.; Pontone, Gregory M.; Chou, Kelvin L.; Umeh, Chizoba; Mari, Zoltan; Boyd, James

2017-01-01

IMPORTANCE Greater body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) is associated with improved survival among persons with Huntington disease or amyotrophic lateral sclerosis. Weight loss is common among persons with Parkinson disease (PD) and is associated with worse quality of life. OBJECTIVE To explore the association between change in BMI, Unified Parkinson’s Disease Rating Scale (UPDRS) motor and total scores, and survival among persons with PD and to test whether there is a positive association between BMI at randomization and survival. DESIGN, SETTING, AND PARTICIPANTS Secondary analysis (from May 27, 2014, to October 13, 2015) of longitudinal data (3–6 years) from 1673 participants who started the National Institute of Neurological Disorders and Stroke Exploratory Trials in PD Long-term Study-1 (NET-PD LS-1). This was a double-blind randomized placebo-controlled clinical trial of creatine monohydrate (10 g/d) that was performed at 45 sites throughout the United States and Canada. Participants with early (within 5 years of diagnosis) and treated (receiving dopaminergic therapy) PD were enrolled from March 2007 to May 2010 and followed up until September 2013. MAIN OUTCOMES AND MEASURES Change across time in motor UPDRS score, change across time in total UPDRS score, and time to death. Generalized linear mixed models were used to estimate the effect of BMI on the change in motor and total UPDRS scores after controlling for covariates. Survival was analyzed using Cox proportional hazards models of time to death. A participant’s BMI was measured at randomization, and BMI trajectory groups were classified according to whether participants experienced weight loss (“decreasing BMI”), weight stability (“stable BMI”), or weight gain (“increasing BMI”) during the study. RESULTS Of the 1673 participants (mean [SD] age, 61.7 [9.6] years; 1074 [64.2%] were male), 158 (9.4%) experienced weight loss (decreasing BMI), whereas 233 (13.9%) experienced weight gain (increasing BMI). After adjusting for covariates, we found that the weight-loss group’s mean (SE) motor UPDRS score increased by 1.48 (0.28) (P < .001) more points per visit than the weight-stable group’s mean (SE) motor UPDRS score. The weight-gain group’s mean (SE) motor UPDRS score decreased by −0.51 (0.24) (P = .03) points per visit, relative to the weight-stable group. While there was an unadjusted difference in survival between the 3 BMI trajectory groups (log-rank P < .001), this was not significant after adjusting for covariates. CONCLUSIONS AND RELEVANCE Change in BMI was inversely associated with change in motor and total UPDRS scores in the NET-PD LS-1. Change in BMI was not associated with survival; however, these results were limited by the low number of deaths in the NET-PD LS-1. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00449865 PMID:26751506

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

PubMed

Wills, Anne-Marie A; Pérez, Adriana; Wang, Jue; Su, Xiao; Morgan, John; Rajan, Suja S; Leehey, Maureen A; Pontone, Gregory M; Chou, Kelvin L; Umeh, Chizoba; Mari, Zoltan; Boyd, James

2016-03-01

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

Quantitative Susceptibility Mapping of the Midbrain in Parkinson’s Disease

PubMed Central

Du, Guangwei; Liu, Tian; Lewis, Mechelle M.; Kong, Lan; Wang, Yi; Connor, James; Mailman, Richard B.; Huang, Xuemei

2017-01-01

Background Parkinson’s disease (PD) is marked pathologically by dopamine neuron loss and iron overload in the substantia nigra pars compacta. Midbrain iron content is reported to be increased in PD based on magnetic resonance imaging (MRI) R2* changes. Because quantitative susceptibility mapping is a novel MRI approach to measure iron content, we compared it with R2* for assessing midbrain changes in PD. Methods Quantitative susceptibility mapping and R2* maps were obtained from 47 PD patients and 47 healthy controls. Midbrain susceptibility and R2* values were analyzed by using both voxel-based and region-of-interest approaches in normalized space, and analyzed along with clinical data, including disease duration, Unified Parkinson’s Disease Rating Scale (UPDRS) I, II, and III sub-scores, and levodopa-equivalent daily dosage. All studies were done while PD patients were “on drug.” Results Compared with controls, PD patients showed significantly increased susceptibility values in both right (cluster size = 106 mm3) and left (164 mm3) midbrain, located ventrolateral to the red nucleus that corresponded to the substantia nigra pars compacta. Susceptibility values in this region were correlated significantly with disease duration, UPDRS II, and levodopa-equivalent daily dosage. Conversely, R2* was increased significantly only in a much smaller region (62 mm3) of the left lateral substantia nigra pars compacta and was not significantly correlated with clinical parameters. Conclusion The use of quantitative susceptibility mapping demonstrated marked nigral changes that correlated with clinical PD status more sensitively than R2*. These data suggest that quantitative susceptibility mapping may be a superior imaging biomarker to R2* for estimating brain iron levels in PD. PMID:26362242

Use of Game Console for Rehabilitation of Parkinson's Disease.

PubMed

Özgönenel, Levent; Çağırıcı, Sultan; Çabalar, Murat; Durmuşoğlu, Gülis

2016-07-01

Parkinson's disease (PD) predisposes to falls due to postural instability and decreased coordination. Postural and coordination exercises could ameliorate the incoordination and decrease falls. In this study, we explored the efficiency of a game console as an adjunct to an exercise program in treating incoordination in patients with PD. Case-control study. In this single-blind, prospective clinical trial, rehabilitation with the Xbox (Microsoft; Washington, USA) game console was used as an adjunct to a standard rehabilitation program. Thirty-three patients with PD at stages 1-3 were enrolled in the study. All patients received the three-times weekly exercise program and electrotherapy to back and hip extensors for 5 weeks. Study patients played catch the ball and obstacle games on the Xbox in addition to the standard exercise program. Patients were evaluated based on the scores from the Timed Up-and-Go Test, the Berg Balance Scale (BBS), and the Unified Parkinson's Disease Rating Scale-II (UPDRS-II). Post-treatment scores were compared between groups. Thirty-three patients were enrolled in the study (15 in the game-console group, and 18 controls). Patients in both groups had improvements in all scores. The end-of-treatment scores were significantly better in the study group compared to the control group in all parameters: UPDRS (10±5 versus 16±6, p=0.002), BBS (53±4 versus 47±8, p=0.004), and TUG (11±4 seconds versus 20±8 seconds, p<0.001). Game-exercise with a game-console was noted to be a significant adjunct to the rehabilitation program in patients with PD in this study.

Long-term safety and tolerability of rotigotine transdermal system in patients with early-stage idiopathic Parkinson's disease: a prospective, open-label extension study.

PubMed

Elmer, Lawrence W; Surmann, Erwin; Boroojerdi, Babak; Jankovic, Joseph

2012-06-01

This prospective, open-label extension (SP702; NCT00594165) of a 6-month double-blind, randomized study investigated the long-term safety and tolerability of rotigotine transdermal system in early Parkinson's disease (PD). Patients with early-stage idiopathic PD received transdermal rotigotine for up to 6 years at optimal dose (up to 16 mg/24h). Adjunctive levodopa was allowed. Primary outcomes included adverse events (AEs) and extent of rotigotine exposure. Other outcomes included time to levodopa, incidence of dyskinesias, and efficacy using the Unified Parkinson's Disease Rating Scale (UPDRS) II+III total score. Of 217 patients entering the open-label study, 47% were still in the study upon closure; 24% withdrew because of AEs and 6% because of lack of efficacy. The median exposure to rotigotine was 1910 days (≈ 5 years, 3 months; range 1-2188 days). Most common AEs were somnolence (23% per patient-year), falls (17%), peripheral edema (14%), nausea (12%), and application site reactions (ASRs; 12%). 3% withdrew because of ASRs. 26% patients did not initiate levodopa; of those who did, fewer than half started levodopa in the first year. Dyskinesias were reported by 25% patients; the majority (83%) reported their first episode after initiating levodopa. Mean UPDRS II+III total scores remained below double-blind baseline for up to 2 years of open-label treatment. This is the longest interventional study of rotigotine conducted to date. Transdermal rotigotine was generally well tolerated for up to 6 years; AEs reported were similar to those observed in shorter studies and led to discontinuation in only 24% patients. Copyright © 2012 Elsevier Ltd. All rights reserved.

Improved clinical status, quality of life, and walking capacity in Parkinson's disease after body weight-supported high-intensity locomotor training.

PubMed

Rose, Martin H; Løkkegaard, Annemette; Sonne-Holm, Stig; Jensen, Bente R

2013-04-01

To evaluate the effect of body weight-supported progressive high-intensity locomotor training in Parkinson's disease (PD) on (1) clinical status; (2) quality of life; and (3) gait capacity. Open-label, fixed sequence crossover study. University motor control laboratory. Patients (N=13) with idiopathic PD (Hoehn and Yahr stage 2 or 3) and stable medication use. Patients completed an 8-week (3 × 1h/wk) training program on a lower-body positive-pressure treadmill. Body weight support was used to facilitate increased intensity and motor challenges during treadmill training. The training program contained combinations of (1) running and walking intervals, (2) the use of sudden changes (eg, in body weight support and speed), (3) different types of locomotion (eg, chassé, skipping, and jumps), and (4) sprints at 50 percent body weight. The Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Parkinson's Disease Questionnaire-39 items (PDQ-39), and the six-minute walk test were conducted 8 weeks before and pre- and posttraining. At the end of training, statistically significant improvements were found in all outcome measures compared with the control period. Total MDS-UPDRS score changed from (mean ± 1SD) 58±18 to 47±18, MDS-UPDRS motor part score changed from 35±10 to 29±12, PDQ-39 summary index score changed from 22±13 to 13±12, and the six-minute walking distance changed from 576±93 to 637±90m. Body weight-supported progressive high-intensity locomotor training is feasible and well tolerated by patients with PD. The training improved clinical status, quality of life, and gait capacity significantly. Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Dopa-decarboxylase gene polymorphisms affect the motor response to L-dopa in Parkinson's disease.

PubMed

Devos, David; Lejeune, Stéphanie; Cormier-Dequaire, Florence; Tahiri, Khadija; Charbonnier-Beaupel, Fanny; Rouaix, Nathalie; Duhamel, Alain; Sablonnière, Bernard; Bonnet, Anne-Marie; Bonnet, Cecilia; Zahr, Noel; Costentin, Jean; Vidailhet, Marie; Corvol, Jean-Christophe

2014-02-01

In Parkinson's disease (PD), the response to L-dopa is highly variable and unpredictable. The major pathway for dopamine synthesis from L-dopa is decarboxylation by aromatic L-amino acid decarboxylase (AAAD, encoded by the DDC gene). To determine the motor response to L-dopa in PD patients as a function of the DDC gene promoter polymorphisms (rs921451 T > C polymorphism (DDC(T/C)) and rs3837091 AGAG del (DDC(AGAG/-))). Thirty-three Caucasian PD patients underwent an acute l-dopa challenge together with the peripheral AAAD inhibitor benserazide and were genotyped for rs921451 and rs3837091. The primary efficacy criterion was the motor response to L-dopa, as estimated by the area under the curve for the change in the Unified Parkinson's Disease Rating Scale part III (UPDRS) score relative to baseline (AUCΔUPDRS) in the 4 h following L-dopa administration. Secondary endpoints were pharmacokinetic parameters for plasma levels of L-dopa and dopamine. Investigators and patients were blinded to genotypes data throughout the study. When adjusted for the L-dopa dose, the AUCΔUPDRS was significantly lower in DDC(CC/CT) patients (n = 14) than in DDC(TT) patients (n = 19) and significantly lower in DDC(-/- or AGAG/-) patients (n = 8) than in DDC(AGAG/AGAG) patients (n = 25). There were no significant intergroup differences in plasma pharmacokinetic parameters for L-dopa and dopamine. The rs921451 and rs3837091 polymorphisms of the DDC gene promoter influence the motor response to L-dopa but do not significantly change peripheral pharmacokinetic parameters for L-dopa and dopamine. Our results suggest that DDC may be a genetic modifier of the l-dopa response in Parkinson's disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

The relationship between depression and regional cerebral blood flow in Parkinson's disease and the effect of selegiline treatment.

PubMed

Imamura, K; Okayasu, N; Nagatsu, T

2011-07-01

We examined the relationship between severity of depression in Parkinson's disease (PD) and regional cerebral blood flow (rCBF) using single photon emission computed tomography (SPECT) and the reaction to levodopa-selegiline combination therapy. We evaluated 52 patients with PD and nine age-matched controls with SPECT and the Unified Parkinson's Disease Rating Scale (UPDRS) part III, Mini-Mental State Examination (MMSE), and Beck Depression Inventory (BDI) to evaluate depression severity and its connection with rCBF. Furthermore, we examined rCBF in patients with PD treated with levodopa with or without selegiline. A significant fall in rCBF was observed in the bilateral posterior cingulate, hippocampus, and cuneus and the superior parietal and primary visual areas in PD patients with minor depression and in all regions in those with major depression. Elevations in UPDRS part III and BDI scores and falls in MMSE scores were of significantly lower magnitude in the levodopa-selegiline group than in the levodopa group. Whole brain rCBF fell significantly less in the levodopa-selegiline group than in the levodopa group. These results indicate that selegiline controlled not only worsening of motor function and cognitive function in PD but also aggravation of minor depression, and restrained a fall in whole brain rCBF. © 2010 John Wiley & Sons A/S.

Deep brain stimulation of the subthalamic nucleus improves pain in Parkinson's disease.

PubMed

Pellaprat, Jean; Ory-Magne, Fabienne; Canivet, Cindy; Simonetta-Moreau, Marion; Lotterie, Jean-Albert; Radji, Fatai; Arbus, Christophe; Gerdelat, Angélique; Chaynes, Patrick; Brefel-Courbon, Christine

2014-06-01

In Parkinson's disease (PD), chronic pain is a common symptom which markedly affects the quality of life. Some physiological arguments proposed that Deep Brain Stimulation of the Subthalamic Nucleus (STN-DBS) could improve pain in PD. We investigated in 58 PD patients the effect of STN-DBS on pain using the short McGill Pain Questionnaire and other pain parameters such as the Bodily discomfort subscore of the Parkinson's disease Questionnaire 39 and the Unified Parkinson's Disease Rating Scale section II (UPDRS II) item 17. All pain scores were significantly improved 12 months after STN-DBS. This improvement was not correlated with motor improvement, depression scores or L-Dopa reduction. STN-DBS induced a substantial beneficial effect on pain in PD, independently of its motor effects and mood status of patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Another face of placebo: The lessebo effect in Parkinson disease

PubMed Central

Mestre, Tiago A.; Shah, Prakesh; Marras, Connie; Tomlinson, George

2014-01-01

Objective: To study the impact of negative expectation related to receiving a placebo (the “lessebo effect”) on efficacy outcome measures of symptomatic treatments in Parkinson disease (PD). Methods: We conducted meta-analyses of double-blind randomized controlled trials (RCTs) of dopamine agonists in PD and compared the pooled mean score change of the motor section of the Unified Parkinson's Disease Rating Scale (mUPDRS) across active treatment arms according to the presence of a placebo arm or the probability of placebo assignment (0%, <50%, and 50%) of the original RCT. A mixed-effects model was used. Heterogeneity was assessed by subgroup analyses and meta-regression modeling. Results: A total of 28 study arms were extracted from active-controlled trials (3,277 patients) and 42 from placebo-controlled trials (4,554 patients). The overall difference between groups in the pooled mean score change in the mUPDRS was 1.6 units (95% confidence interval [CI] 0.2, 3.0; p = 0.023), in favor of the active-controlled group. In subgroup analyses, this difference was of higher magnitude in the early PD group without motor fluctuations (3.3 mUPDRS units, 95% CI 1.1, 5.4; p = 0.003) and for study duration ≤12 weeks (4.1 mUPDRS units, 95% CI 1.0, 7.2; p = 0.009). There was no between-group difference using probability of placebo assignment as criterion. Conclusions: This study shows that the use of a placebo can be associated with a clinically significant reduction in the magnitude of change of the mUPDRS after an active treatment in RCTs for PD. These new findings have potential implications in the development of new treatments and appraisal of current treatment options for PD and possibly for other neurologic disorders. PMID:24658930

Effects of disease duration on the clinical features and brain glucose metabolism in patients with mixed type multiple system atrophy.

PubMed

Lyoo, C H; Jeong, Y; Ryu, Y H; Lee, S Y; Song, T J; Lee, J H; Rinne, J O; Lee, M S

2008-02-01

To study the effect of disease duration on the clinical, neuropsychological and [(18)F]-deoxyglucose (FDG) PET findings in patients with mixed type multiple system atrophy (MSA), this study included 16 controls and 37 mixed-type MSA patients with a shorter than a 3-year history of cerebellar or parkinsonian symptoms. We classified the patients into three groups according to the duration of parkinsonian or cerebellar symptoms (Group I =

Rotigotine transdermal system and evaluation of pain in patients with Parkinson's disease: a post hoc analysis of the RECOVER study.

PubMed

Kassubek, Jan; Chaudhuri, Kallol Ray; Zesiewicz, Theresa; Surmann, Erwin; Boroojerdi, Babak; Moran, Kimberly; Ghys, Liesbet; Trenkwalder, Claudia

2014-03-06

Pain is a troublesome non-motor symptom of Parkinson's disease (PD). The RECOVER (Randomized Evaluation of the 24-hour Coverage: Efficacy of Rotigotine; Clintrials.gov: NCT00474058) study demonstrated significant improvements in early-morning motor function (UPDRS III) and sleep disturbances (PDSS-2) with rotigotine transdermal system. Improvements were also reported on a Likert pain scale (measuring any type of pain). This post hoc analysis of RECOVER further evaluates the effect of rotigotine on pain, and whether improvements in pain may be attributable to benefits in motor function or sleep disturbance. PD patients with unsatisfactory early-morning motor impairment were randomized to optimal-dose (up to 16 mg/24 h) rotigotine or placebo, maintained for 4 weeks. Pain was assessed in the early-morning using an 11-point Likert pain scale (rated average severity of pain (of any type) over the preceding 12 hours from 0 [no pain] to 10 [worst pain ever experienced]). Post hoc analyses for patients reporting 'any' pain (pain score ≥1) at baseline, and subgroups reporting 'mild' (score 1-3), and 'moderate-to-severe' pain (score ≥4) were performed. Likert pain scale change from baseline in rotigotine-treated patients was further analyzed based on a UPDRS III/PDSS-2 responder analysis (a responder defined as showing a ≥30% reduction in early morning UPDRS III total score or PDSS-2 total score). As post hoc analyses, all p values presented are exploratory. Of 267 patients with Likert pain data (178 rotigotine, 89 placebo), 187 (70%) reported 'any' pain; of these 87 (33%) reported 'mild', and 100 (37%) 'moderate-to-severe' pain. Change from baseline pain scores decreased with rotigotine compared with placebo in patients with 'any' pain (-0.88 [95% CI: -1.56, -0.19], p = 0.013), and in the subgroup with 'moderate-to-severe' pain (-1.38 [-2.44, -0.31], p = 0.012). UPDRS III or PDSS-2 responders showed greater improvement in pain than non-responders. The results from this post hoc analysis of the RECOVER study suggest that pain was improved in patients with PD treated with rotigotine; this may be partly attributable to benefits in motor function and sleep disturbances. Prospective studies are warranted to investigate this potential benefit and the clinical relevance of these findings.

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

PubMed Central

Gill, Chandler E.; Allen, Laura A.; Konrad, Peter E.; Davis, Thomas L.; Bliton, Mark J.; Finder, Stuart G.; Tramontana, Michael G.; Kao, C. Chris; Remple, Michael S.; Bradenham, Courtney H.; Charles, P. David

2011-01-01

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. Our team is conducting a randomized pilot trial investigating DBS in early PD. This report describes one participant who received bilateral STN-DBS. Materials/Methods Thirty subjects have been randomized to either optimal drug therapy (ODT) or DBS + ODT. Microelectrode recordings from the STN and substantia nigra (SN) 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 SN ratio of neuronal activity than advanced PD patients, and higher firing rate than non-PD patients. The subject's ON total UPDRS and UPDRS-III scores improved during the two-year follow-up, while his OFF UPDRS-III score and levodopa equivalent daily dose (LEDD) 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. PMID:21939467

Therapeutic singing as an early intervention for swallowing in persons with Parkinson's disease.

PubMed

Stegemöller, E L; Hibbing, P; Radig, H; Wingate, J

2017-04-01

For persons with Parkinson's disease (PD), secondary motor symptoms such as swallow impairment impact the quality of life and are major contributors to mortality. There is a present need for therapeutic interventions aimed at improving swallow function during the early stages of PD. The purpose of this pilot study was to examine the effects of a group therapeutic singing intervention on swallowing in persons with PD with no significant dysphagia symptoms. Cohort study. University in the United States. Twenty-four participants with PD. Eight weeks of group therapeutic singing. Electromyography (EMG) was used to assess muscle activity associated with swallow pre and post the group singing intervention. Swallow quality of life (SWAL-QOL) and the Unified Parkinson's Disease Rating Scale (UPDRS) were also obtained pre- and post-intervention. Participants reported minimal difficulty with swallowing, yet results revealed a significant increase in EMG outcome measures, as well as significant improvement in UPDRS total and UPDRS motor scores. No significant differences were revealed for SWAL-QOL. Increases in EMG timing measures may suggest that group singing results in the prolongation of laryngeal elevation, protecting the airway from foreign material for longer periods of time during swallow. Combined with the improvement in UPDRS clinical measures, therapeutic singing may be an engaging early intervention strategy to address oropharyngeal dysphagia while also benefiting additional clinical symptoms of PD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Parkinson's Patients with Dyskinesia Switched from Immediate Release Amantadine to Open‐label ADS‐5102

PubMed Central

Fahn, Stanley; Pahwa, Rajesh; Tanner, Caroline M.; Espay, Alberto J.; Trenkwalder, Claudia; Adler, Charles H.; Patni, Rajiv; Johnson, Reed

2018-01-01

Abstract Background ADS‐5102 (amantadine) extended release capsules (GOCOVRI™) are a treatment for dyskinesia in patients with Parkinson's disease (PD). ADS‐5102 reduced dyskinesia and OFF time in phase 3 controlled trials of up to six months. Amantadine immediate release (IR) is used for dyskinesia, but suboptimal durability and tolerability limit its clinical utility. Methods In an ongoing, open‐label, phase 3 study in the US and Western Europe (NCT02202551), patients with PD received 274 mg of ADS‐5102 (equivalent to 340 mg amantadine HCl) once daily at bedtime for up to two years. Study outcomes included safety and assessment of motor complications, as measured by the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) Part IV. This manuscript focuses on those patients switched to ADS‐5102 from amantadine IR. Results in two groups of patients who previously completed a randomized controlled trial (EASE LID or EASE LID 3) are also presented according to use of ADS‐5102 or placebo in that study before enrollment in the open‐label study. Results Change in MDS‐UPDRS Part IV at week 8 was –0.3 in the previous ADS‐5102 subgroup (n = 61), –3.4 in the previous placebo subgroup (n = 79), and –3.4 in the previous amantadine IR subgroup (n = 32). Effects were maintained to week 64. In the previous amantadine IR subgroup (mean treatment duration, 2.5 years), mean amantadine IR dose was 221 mg. Safety data were consistent with previous randomized controlled trials of ADS‐5102. Conclusion These open‐label data suggest ADS‐5102 provides incremental reduction from baseline in MDS‐UDPRS Part IV score in patients switched directly from amantadine IR, without exacerbating adverse events.

Motor Function in Former Professional Football Players with History of Multiple Concussions.

PubMed

Tarazi, Apameh; Tator, Charles H; Wennberg, Richard; Ebraheem, Ahmed; Green, Robin E A; Collela, Brenda; Saverino, Christina; Khodadadi, Mozghan; Misquitta, Karen; Tartaglia, Maria Carmela

2018-04-15

The objective of this study was to assess the incidence of motor impairment in former professional Canadian Football League (ex-CFL) players with multiple concussions. We investigated motor symptoms and signs in 45 ex-CFL players with multiple concussions and 25 age- and education-matched healthy controls with no history of concussion. Neurological assessment included items from the SCAT3 (Sport Concussion Assessment Tool 3) and the Unified Parkinson's Disease Rating Scale part III (UPDRS-Part III). A performance-based measurement of manual motor function was undertaken using the Grooved Pegboard test. Cognition was measured with patient-reported outcomes for memory, executive and behavioral symptoms as well as performance-based measures of memory and executive function. Symptoms of anxiety and depression were measured using the Personality Assessment Inventory. There was no significant difference between the ex-CFL players and controls on the UPDRS-Part III scores, and neither group reported clinically significant motor complaints. Ex-CFL players did not perform differently from control subjects on the Grooved Pegboard test. In contrast, with regard to cognitive and mood testing, players were more symptomatic: The ex-CFL players reported significantly more memory (77.8% vs. 16%, respectively, p < 0.001), executive (53.3% vs. 8%, respectively, p < 0.001), and behavioral symptoms (66.7% vs. 20%, respectively, p < 0.001). No significant differences were found when comparing ex-CFL players and controls in performance on memory and executive tests. In summary, in a group of retired CFL players who self-reported declines in memory, executive and behavioral symptoms, no motor symptoms were reported and no motor signs were detected.

Fatigue and excessive daytime sleepiness in idiopathic Parkinson's disease differently correlate with motor symptoms, depression and dopaminergic treatment.

PubMed

Valko, P O; Waldvogel, D; Weller, M; Bassetti, C L; Held, U; Baumann, C R

2010-12-01

A comprehensive study of both fatigue and excessive daytime sleepiness (EDS) in association with Parkinson's disease (PD)-related symptoms and treatment has not been performed yet. To assess the frequency and severity of fatigue and EDS in patients with idiopathic PD and to study their relation to motor and non-motor symptoms and dopaminergic treatment. We prospectively assessed Fatigue Severity Scale (FSS) scores, Epworth Sleepiness Scale (ESS) scores, Beck Depression Inventory (BDI) scores, severity (Unified PD Rating Scale, UPDRS, part III; Hoehn & Yahr staging) and duration of the disease, and the current dopaminergic treatment in 88 consecutive patients with idiopathic PD. Fatigue was found in 52 (59%), EDS in 42 (48%), and both complaints in 31 (35%) patients. Fatigued patients had higher UPDRS III scores (23.5 ± 11.1 vs. 18.6 ± 7.6, P = 0.03), higher Hoehn & Yahr staging (2.4 ± 0.9 vs. 2.1 ± 0.7, P = 0.03), and higher BDI scores (13.4 ± 7.1 vs. 9.1 ± 5.8, P = 0.004) than non-fatigued patients. In contrast, UPDRS III, Hoehn & Yahr, and BDI scores did not differ between patients with or without EDS. However, the type of dopaminergic treatment (levodopa monotherapy versus combination of levodopa/dopamine agonists) was associated with significant differences in ESS (8.5 ± 5.2 vs. 10.8 ± 4.3, P = 0.04), but not FSS scores (4.1 ± 1.5 vs. 4.3 ± 1.5, P = 0.55). Disease duration correlated with ESS scores (r = 0.32, P = 0.003), but not with FSS scores (r = -0.02, P = 0.82). In PD, there is a significant overlap of fatigue and EDS, but the two symptoms are differently correlated with the severity of motor symptoms, disease duration, depression, and dopaminergic treatment. © 2010 The Author(s). European Journal of Neurology © 2010 EFNS.

Rotigotine transdermal system and evaluation of pain in patients with Parkinson’s disease: a post hoc analysis of the RECOVER study

PubMed Central

2014-01-01

Background Pain is a troublesome non-motor symptom of Parkinson’s disease (PD). The RECOVER (Randomized Evaluation of the 24-hour Coverage: Efficacy of Rotigotine; Clintrials.gov: NCT00474058) study demonstrated significant improvements in early-morning motor function (UPDRS III) and sleep disturbances (PDSS-2) with rotigotine transdermal system. Improvements were also reported on a Likert pain scale (measuring any type of pain). This post hoc analysis of RECOVER further evaluates the effect of rotigotine on pain, and whether improvements in pain may be attributable to benefits in motor function or sleep disturbance. Methods PD patients with unsatisfactory early-morning motor impairment were randomized to optimal-dose (up to 16 mg/24 h) rotigotine or placebo, maintained for 4 weeks. Pain was assessed in the early-morning using an 11-point Likert pain scale (rated average severity of pain (of any type) over the preceding 12 hours from 0 [no pain] to 10 [worst pain ever experienced]). Post hoc analyses for patients reporting ‘any’ pain (pain score ≥1) at baseline, and subgroups reporting ‘mild’ (score 1–3), and ‘moderate-to-severe’ pain (score ≥4) were performed. Likert pain scale change from baseline in rotigotine-treated patients was further analyzed based on a UPDRS III/PDSS-2 responder analysis (a responder defined as showing a ≥30% reduction in early morning UPDRS III total score or PDSS-2 total score). As post hoc analyses, all p values presented are exploratory. Results Of 267 patients with Likert pain data (178 rotigotine, 89 placebo), 187 (70%) reported ‘any’ pain; of these 87 (33%) reported ‘mild’, and 100 (37%) ‘moderate-to-severe’ pain. Change from baseline pain scores decreased with rotigotine compared with placebo in patients with ‘any’ pain (-0.88 [95% CI: -1.56, -0.19], p = 0.013), and in the subgroup with ‘moderate-to-severe’ pain (-1.38 [-2.44, -0.31], p = 0.012). UPDRS III or PDSS-2 responders showed greater improvement in pain than non-responders. Conclusions The results from this post hoc analysis of the RECOVER study suggest that pain was improved in patients with PD treated with rotigotine; this may be partly attributable to benefits in motor function and sleep disturbances. Prospective studies are warranted to investigate this potential benefit and the clinical relevance of these findings. PMID:24602411

A population-based study of parkinsonism in an Amish community.

PubMed

Racette, Brad A; Good, Laura M; Kissel, Abigail M; Criswell, Susan R; Perlmutter, Joel S

2009-01-01

Parkinson's disease (PD) is a neurodegenerative disorder with unknown cause. Genetic mutations account for a minority of cases but the role of environmental factors is unclear. We performed a population-based screening for PD in subjects in an Amish community over age 60. PD was diagnosed using standard clinical criteria and the Unified Parkinson Disease Rating Scale motor subsection 3 (UPDRS3). Community prevalence was calculated. We constructed a community pedigree and calculated kinship coefficients, a measure of relatedness between 2 subjects, for every pair of subjects in diagnostic categories: clinically definite PD, UPDRS3 score >9, Mini-Mental State Exam (MMSE) score <25, and normal. Of 262 eligible subjects, 213 agreed to participate, 15 had PD, 43 had MMSE <25, 73 had UPDRS3 >9. The prevalence of PD was 5,703/100,000 with increasing prevalence in every decade of age. Excluding first-degree relatives, normal subjects were more related to each other (0.0102, SD = 0.0266) than subjects with clinically definite PD (0.0054, SD = 0.0100; p = 0.00003), subjects with UPDRS >9 (0.0076, SD = 0.0155; p = 0.00001), and subjects with MMSE <25 (0.0090, SD = 0.0180; p = 0.00003). PD and parkinsonian signs are common in this population and the prevalence increases with age. The finding that subjects with PD were not more related than normal subjects suggests that environmental factors may contribute to the parkinsonian phenotype in this community. Copyright 2009 S. Karger AG, Basel.

Increased risk of parkinsonism associated with welding exposure.

PubMed

Racette, Brad A; Criswell, Susan R; Lundin, Jessica I; Hobson, Angela; Seixas, Noah; Kotzbauer, Paul T; Evanoff, Bradley A; Perlmutter, Joel S; Zhang, Jing; Sheppard, Lianne; Checkoway, Harvey

2012-10-01

Manganese (Mn), an established neurotoxicant, is a common component of welding fume. The neurological phenotype associated with welding exposures has not been well described. Prior epidemiologic evidence linking occupational welding to parkinsonism is mixed, and remains controversial. This was a cross-sectional and nested case-control study to investigate the prevalence and phenotype of parkinsonism among 811 shipyard and fabrication welders recruited from trade unions. Two reference groups included 59 non-welder trade workers and 118 newly diagnosed, untreated idiopathic PD patients. Study subjects were examined by a movement disorders specialist using the Unified Parkinson Disease Rating Scale motor subsection 3 (UPDRS3). Parkinsonism cases were defined as welders with UPDRS3 score ≥15. Normal was defined as UPDRS3<6. Exposure was classified as intensity adjusted, cumulative years of welding. Adjusted prevalence ratios for parkinsonism were calculated in relation to quartiles of welding years. The overall prevalence estimate of parkinsonism was 15.6% in welding exposed workers compared to 0% in the reference group. Among welders, we observed a U-shaped dose-response relation between weighted welding exposure-years and parkinsonism. UPDRS3 scores for most domains were similar between welders and newly diagnosed idiopathic Parkinson disease (PD) patients, except for greater frequency of rest tremor and asymmetry in PD patients. This work-site based study among welders demonstrates a high prevalence of parkinsonism compared to nonwelding-exposed workers and a clinical phenotype that overlaps substantially with PD. Copyright © 2012 Elsevier Inc. All rights reserved.

Increased risk of parkinsonism associated with welding exposure

PubMed Central

Racette, Brad A.; Criswell, Susan R.; Lundin, Jessica I.; Hobson, Angela; Seixas, Noah; Kotzbauer, Paul T.; Evanoff, Bradley A.; Perlmutter, Joel S.; Zhang, Jing; Sheppard, Lianne; Checkoway, Harvey

2013-01-01

Objective Manganese (Mn), an established neurotoxicant, is a common component of welding fume. The neurological phenotype associated with welding exposures has not been well described. Prior epidemiologic evidence linking occupational welding to parkinsonism is mixed, and remains controversial. Methods This was a cross-sectional and nested case–control study to investigate the prevalence and phenotype of parkinsonism among 811 shipyard and fabrication welders recruited from trade unions. Two reference groups included 59 non-welder trade workers and 118 newly diagnosed, untreated idiopathic PD patients. Study subjects were examined by a movement disorders specialist using the Unified Parkinson Disease Rating Scale motor subsection 3 (UPDRS3). Parkinsonism cases were defined as welders with UPDRS3 score ≥15. Normal was defined as UPDRS3 < 6. Exposure was classified as intensity adjusted, cumulative years of welding. Adjusted prevalence ratios for parkinsonism were calculated in relation to quartiles of welding years. Results The overall prevalence estimate of parkinsonism was 15.6% in welding exposed workers compared to 0% in the reference group. Among welders, we observed a U-shaped dose–response relation between weighted welding exposure-years and parkinsonism. UPDRS3 scores for most domains were similar between welders and newly diagnosed idiopathic Parkinson disease (PD) patients, except for greater frequency of rest tremor and asymmetry in PD patients. Conclusion This work-site based study among welders demonstrates a high prevalence of parkinsonism compared to nonwelding-exposed workers and a clinical phenotype that overlaps substantially with PD. PMID:22975422

Implantation of Spheramine in advanced Parkinson's disease (PD).

PubMed

Bakay, Roy A E; Raiser, Cathy D; Stover, Natividad P; Subramanian, Thyagarajan; Cornfeldt, Michael L; Schweikert, Alfred W; Allen, Richard C; Watts, Ray

2004-01-01

Evaluation of the safety and efficacy of unilateral stereotactic implantation of cultured human retinal pigment epithelial (hRPE) cells attached to microcarriers (Spheramine) in patients with advanced PD in an open label pilot study. Six patients with advanced PD (3 males; 3 females; mean age 52.2 years; mean duration of PD 10.2 years; mean Hoehn and Yahr stage "off" 3.75) were assessed at baseline and post-operatively using the modified CAPIT. Each patient underwent MRI-guided stereotactic transplantation of 325,000 hRPE cells attached to microcarriers in 5 tracts, 5 mm apart in the post-commissural putamen contralateral to the most affected side. Immunosuppression was not used. The UPDRS Motor (UPDR-M) score in the practically defined "off" state was the primary outcome measure. At 6 months post-op, the mean UPDRS-M (off) score improved to 35 (34%) from a pre-op baseline mean of 52 (p <.001). Secondary outcome measures improved including the total UPDRS (33%), Timed Motor Tests (on, 14%; off, 23%), PDQ39 QOL (30%), and Schwab and England score (on, 11%; off, 30%). Bilateral improvements have been observed in motor symptoms, with the greatest effect seen contralateral to the implants. Three of six patients currently have lower Dyskinesia Rating Scale scores than at baseline, while the scores of the other three are unchanged from baseline values. No "off-state" dyskinesias have been observed. Thus Spheramine implantation therapy appears to be safe and well tolerated for 6 months post-implantation.

Polestriding Intervention Improves Gait and Axial Symptoms in Mild to Moderate Parkinson Disease.

PubMed

Krishnamurthi, Narayanan; Shill, Holly; O'Donnell, Darolyn; Mahant, Padma; Samanta, Johan; Lieberman, Abraham; Abbas, James

2017-04-01

To evaluate the effects of 12-week polestriding intervention on gait and disease severity in people with mild to moderate Parkinson disease (PD). A-B-A withdrawal study design. Outpatient movement disorder center and community facility. Individuals (N=17; 9 women [53%] and 8 men [47%]; mean age, 63.7±4.9y; range, 53-72y) with mild to moderate PD according to United Kingdom brain bank criteria with Hoehn & Yahr score ranging from 2.5 to 3.0 with a stable medication regimen and ability to tolerate "off" medication state. Twelve-week polestriding intervention with 12-week follow-up. Gait was evaluated using several quantitative temporal, spatial, and variability measures. In addition, disease severity was assessed using clinical scales such as Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn & Yahr scale, and Parkinson's Disease Questionnaire-39. Step and stride lengths, gait speed, and step-time variability were improved significantly (P<.05) because of 12-week polestriding intervention. Also, the UPDRS motor score, the UPDRS axial score, and the scores of UPDRS subscales on walking and balance improved significantly after the intervention. Because increased step-time variability and decreased step and stride lengths are associated with PD severity and an increased risk of falls in PD, the observed improvements suggest that regular practice of polestriding may reduce the risk of falls and improve mobility in people with PD. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Quantifying Short-Term Dynamics of Parkinson’s Disease Using Self-Reported Symptom Data From an Internet Social Network

PubMed Central

Wicks, Paul; Vaughan, Timothy; Pentland, Alex

2013-01-01

Background Parkinson’s disease (PD) is an incurable neurological disease with approximately 0.3% prevalence. The hallmark symptom is gradual movement deterioration. Current scientific consensus about disease progression holds that symptoms will worsen smoothly over time unless treated. Accurate information about symptom dynamics is of critical importance to patients, caregivers, and the scientific community for the design of new treatments, clinical decision making, and individual disease management. Long-term studies characterize the typical time course of the disease as an early linear progression gradually reaching a plateau in later stages. However, symptom dynamics over durations of days to weeks remains unquantified. Currently, there is a scarcity of objective clinical information about symptom dynamics at intervals shorter than 3 months stretching over several years, but Internet-based patient self-report platforms may change this. Objective To assess the clinical value of online self-reported PD symptom data recorded by users of the health-focused Internet social research platform PatientsLikeMe (PLM), in which patients quantify their symptoms on a regular basis on a subset of the Unified Parkinson’s Disease Ratings Scale (UPDRS). By analyzing this data, we aim for a scientific window on the nature of symptom dynamics for assessment intervals shorter than 3 months over durations of several years. Methods Online self-reported data was validated against the gold standard Parkinson’s Disease Data and Organizing Center (PD-DOC) database, containing clinical symptom data at intervals greater than 3 months. The data were compared visually using quantile-quantile plots, and numerically using the Kolmogorov-Smirnov test. By using a simple piecewise linear trend estimation algorithm, the PLM data was smoothed to separate random fluctuations from continuous symptom dynamics. Subtracting the trends from the original data revealed random fluctuations in symptom severity. The average magnitude of fluctuations versus time since diagnosis was modeled by using a gamma generalized linear model. Results Distributions of ages at diagnosis and UPDRS in the PLM and PD-DOC databases were broadly consistent. The PLM patients were systematically younger than the PD-DOC patients and showed increased symptom severity in the PD off state. The average fluctuation in symptoms (UPDRS Parts I and II) was 2.6 points at the time of diagnosis, rising to 5.9 points 16 years after diagnosis. This fluctuation exceeds the estimated minimal and moderate clinically important differences, respectively. Not all patients conformed to the current clinical picture of gradual, smooth changes: many patients had regimes where symptom severity varied in an unpredictable manner, or underwent large rapid changes in an otherwise more stable progression. Conclusions This information about short-term PD symptom dynamics contributes new scientific understanding about the disease progression, currently very costly to obtain without self-administered Internet-based reporting. This understanding should have implications for the optimization of clinical trials into new treatments and for the choice of treatment decision timescales. PMID:23343503

Quantifying short-term dynamics of Parkinson's disease using self-reported symptom data from an Internet social network.

PubMed

Little, Max; Wicks, Paul; Vaughan, Timothy; Pentland, Alex

2013-01-24

Parkinson's disease (PD) is an incurable neurological disease with approximately 0.3% prevalence. The hallmark symptom is gradual movement deterioration. Current scientific consensus about disease progression holds that symptoms will worsen smoothly over time unless treated. Accurate information about symptom dynamics is of critical importance to patients, caregivers, and the scientific community for the design of new treatments, clinical decision making, and individual disease management. Long-term studies characterize the typical time course of the disease as an early linear progression gradually reaching a plateau in later stages. However, symptom dynamics over durations of days to weeks remains unquantified. Currently, there is a scarcity of objective clinical information about symptom dynamics at intervals shorter than 3 months stretching over several years, but Internet-based patient self-report platforms may change this. To assess the clinical value of online self-reported PD symptom data recorded by users of the health-focused Internet social research platform PatientsLikeMe (PLM), in which patients quantify their symptoms on a regular basis on a subset of the Unified Parkinson's Disease Ratings Scale (UPDRS). By analyzing this data, we aim for a scientific window on the nature of symptom dynamics for assessment intervals shorter than 3 months over durations of several years. Online self-reported data was validated against the gold standard Parkinson's Disease Data and Organizing Center (PD-DOC) database, containing clinical symptom data at intervals greater than 3 months. The data were compared visually using quantile-quantile plots, and numerically using the Kolmogorov-Smirnov test. By using a simple piecewise linear trend estimation algorithm, the PLM data was smoothed to separate random fluctuations from continuous symptom dynamics. Subtracting the trends from the original data revealed random fluctuations in symptom severity. The average magnitude of fluctuations versus time since diagnosis was modeled by using a gamma generalized linear model. Distributions of ages at diagnosis and UPDRS in the PLM and PD-DOC databases were broadly consistent. The PLM patients were systematically younger than the PD-DOC patients and showed increased symptom severity in the PD off state. The average fluctuation in symptoms (UPDRS Parts I and II) was 2.6 points at the time of diagnosis, rising to 5.9 points 16 years after diagnosis. This fluctuation exceeds the estimated minimal and moderate clinically important differences, respectively. Not all patients conformed to the current clinical picture of gradual, smooth changes: many patients had regimes where symptom severity varied in an unpredictable manner, or underwent large rapid changes in an otherwise more stable progression. This information about short-term PD symptom dynamics contributes new scientific understanding about the disease progression, currently very costly to obtain without self-administered Internet-based reporting. This understanding should have implications for the optimization of clinical trials into new treatments and for the choice of treatment decision timescales.

A long-term self-managed handwriting intervention for people with Parkinson's disease: results from the control group of a phase II randomized controlled trial.

PubMed

Collett, Johnny; Franssen, Marloes; Winward, Charlotte; Izadi, Hooshang; Meaney, Andy; Mahmoud, Wala; Bogdanovic, Marko; Tims, Martin; Wade, Derick; Dawes, Helen

2017-12-01

To report on the control group of a trial primarily designed to investigate exercise for improving mobility in people with Parkinson's disease (pwP). The control group undertook a handwriting intervention to control for attention and time spent practising a specific activity. Secondary analysis of a two-arm parallel phase II randomized controlled trial with blind assessment. Community. PwP able to walk ⩾100 m and with no contraindication to exercise were recruited from the Thames Valley, UK, and randomized (1:1) to exercise or handwriting, via a concealed computer-generated list. Handwriting was undertaken at home and exercise in community facilities; both were delivered through workbooks with monthly support visits and involved practice for 1 hour, twice weekly, over a period of six months. Handwriting was assessed, at baseline, 3, 6 and 12 months, using a pangram giving writing speed, amplitude (area) and progressive reduction in amplitude (ratio). The Movement Disorder Society (MDS)-Unified Parkinson's Disease Rating Scale (UPDRS) item 2.7 measured self-reported handwriting deficits. In all, 105 pwP were recruited (analysed: n  = 51 handwriting, n  = 54 exercise). A total of 40 pwP adhered to the handwriting programme, most completing ⩾1 session/week. Moderate effects were found for amplitude (total area: d = 0.32; 95% confidence interval (CI): -0.11 to 0.7; P = 0.13) in favour of handwriting over a period of12 months; effects for writing speed and ratio parameters were small ≤0.11. Self-reported handwriting difficulties also favoured handwriting (UPDRS 2.7: odds ratio (OR) = 0.55; 95% CI: 0.34 to 0.91; P = 0.02). No adverse effects were reported. PwP generally adhere to self-directed home handwriting which may provide benefit with minimal risk. Encouraging effects were found in writing amplitude and, moreover, perceived ability.

Clinical Impact and Cost-Effectiveness of an Education Program for PD Patients: A Randomized Controlled Trial

PubMed Central

Ory-Magne, Fabienne; Arcari, Céline; Mohara, Christine; Pourcel, Laure; Derumeaux, Hélène; Bérard, Emilie; Bourrel, Robert; Molinier, Laurent; Brefel-Courbon, Christine

2016-01-01

Background Parkinson’s disease (PD) is characterized by its impact on quality of life, constituting a substantial economic burden on society. Education programs implicating patients more in the management of their illness and complementing medical treatment may be a beneficial adjunct in PD. This study assessed the impact of an education program on quality of life and its cost-effectiveness in PD patients. Methods This single-center, prospective, randomized study assessed an education program consisting of individual and group sessions over a 12-month period. A total of 120 PD patients were assigned to either the Treated by Behavioral Intervention group (TTBI) or the no TTBI group. The primary outcome criterion was quality of life assessed using PDQ39. The Unified Parkinson’s Disease Rating Scale (UPDRS) and psychological status were collected. An economic evaluation was performed, including calculations of incremental cost-effectiveness ratios (ICERs). Results After 12 months of follow-up, changes recorded in the PDQ39 between the groups were not significantly different but better changes were observed in each dimension in the TTBI group compared to the no TTBI group. UPDRS I, II and total score were significantly improved in TTBI group compared to the no TTBI group. Mean annual costs did not differ significantly between the two groups. Conclusion This study suggested that the education program positively impacts the perceived health of PD patients without increasing medical costs. PMID:27685455

Freezing during tapping tasks in patients with advanced Parkinson's disease and freezing of gait.

PubMed

Delval, Arnaud; Defebvre, Luc; Tard, Céline

2017-01-01

Parkinson's disease patients with freezing of gait also experience sudden motor blocks (freezing) during other repetitive motor tasks. We assessed the proportion of patients with advanced PD and freezing of gait who also displayed segmental "freezing" in tapping tasks. Fifteen Parkinson's disease patients with freezing of gait were assessed. Freezing of gait was evaluated using a standardized gait trajectory with the usual triggers. Patients performed repetitive tapping movements (as described in the MDS-UPDRS task) with the hands or the feet in the presence or absence of a metronome set to 4 Hz. Movements were recorded with a video motion system. The primary endpoint was the occurrence of segmental freezing in these tapping tasks. The secondary endpoints were (i) the relationship between segmental episodic phenomena and FoG severity, and (ii) the reliability of the measurements. For the upper limbs, freezing was observed more frequently with a metronome (21% of trials) than without a metronome (5%). For the lower limbs, the incidence of freezing was higher than for the upper limbs, and was again observed more frequently in the presence of an auditory cue (47%) than in its absence (14%). Although freezing of the lower limbs was easily assessed during an MDS-UPDRS task with a metronome, it was not correlated with the severity of freezing of gait (as evaluated during a standardized gait trajectory). Only this latter was a reliable measurement in patients with advanced Parkinson's disease.

Effect of high-frequency repetitive transcranial magnetic stimulation on major depressive disorder in patients with Parkinson's disease.

PubMed

Shin, Hae-Won; Youn, Young C; Chung, Sun J; Sohn, Young H

2016-07-01

Major depressive disorder (MDD) occurs in a small proportion of patients with Parkinson's disease (PD) and reduces their quality of life. We performed a randomized sham-controlled study to evaluate the effect of high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) on MDD in patients with PD. Ten patients participated to a real-rTMS group and eight patients to a sham-rTMS group. Evaluations were performed at baseline, 2 and 6 weeks after rTMS treatment. All participants underwent examinations of depression rating scales, including the Hamilton Rating Scale, the Montgomery-Asberg Depression Rating Scale (MADRS), and the Beck Depression Inventory (BDI) and the motor part of the Unified Parkinson Disease Rating Scale (UPDRS-III). The real-rTMS group had improved scores on HRS and the MADRS after 10 sessions, and these beneficial effects persisted for 6 weeks after the initial session. The BDI score did not change immediately after the sessions. The sham-rTMS group had no significant changes in any of the depression rating scales. The UPDRS-III did not change in either group. HF-rTMS of the left DLPFC is an effective treatment for MDD in patients with PD.

The Clinical Findings Useful for Driving Safety Advice for Parkinson's Disease Patients.

PubMed

Ando, Rina; Iwaki, Hirotaka; Tsujii, Tomoaki; Nagai, Masahiro; Nishikawa, Noriko; Yabe, Hayato; Aiba, Ikuko; Hasegawa, Kazuko; Tsuboi, Yoshio; Aoki, Masashi; Nakashima, Kenji; Nomoto, Masahiro

2018-02-28

Objective We conducted a study to obtain information that could be used to provide Parkinson's disease (PD) patients with appropriate advice on safe driving. Methods Consecutive PD patients who visited our office were studied. Among these patients, those who had experienced driving after being diagnosed with PD were interviewed by neurologists and a trained nurse to investigate their previous car accidents, motor function, cognitive function, sleepiness, levodopa equivalent dose (LED), and emotional dysregulation. The rates of major car accidents before and after the onset of PD were compared. Results Fifteen patients had experienced a major car accident resulting in human injury or serious property damage since the onset of PD. When the rates of major car accidents before and after the onset of PD were compared, the ratio was 4.3 (95% CI 1.9-9.7). The incidence of accidents after the onset of PD was correlated with age, disease duration, LED, the cognitive function (MMSE, MoCA-J), but not the motor symptom score (UPDRS part III at the time of the study). The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP) score was also higher in patients with major car accidents. Conclusion The severity of symptoms (Hoehn-Yahr classification), cognitive function, and disease duration were expected to be risk factors for car accidents. However, the motor symptom score (UPDRS part III) was not associated with the incidence of major car accidents. In addition to a low cognitive function and the severity of symptoms, the QUIP score might be an independent factor that can be referenced when advising PD patients to refrain from driving.

Motor outcome and electrode location in deep brain stimulation in Parkinson's disease.

PubMed

Koivu, Maija; Huotarinen, Antti; Scheperjans, Filip; Laakso, Aki; Kivisaari, Riku; Pekkonen, Eero

2018-05-30

To evaluate the efficacy and adverse effects of subthalamic deep brain stimulation (STN-DBS) in patients with advanced Parkinson's disease (PD) and the possible correlation between electrode location and clinical outcome. We retrospectively reviewed 87 PD-related STN-DBS operations at Helsinki University Hospital (HUH) from 2007 to 2014. The changes of Unified Parkinson's Disease Rating Scale (UPDRS) part III score, Hoehn & Yahr stage, antiparkinson medication, and adverse effects were studied. We estimated the active electrode location in three different coordinate systems: direct visual analysis of MRI correlated to brain atlas, location in relation to the nucleus borders and location in relation to the midcommisural point. At 6 months after operation, both levodopa equivalent doses (LEDs; 35%, Wilcoxon signed-rank test = 0.000) and UPDRS part III scores significantly decreased (38%, Wilcoxon signed-rank test = 0.000). Four patients (5%) suffered from moderate DBS-related dysarthria. The generator and electrodes had to be removed in one patient due to infection (1%). Electrode coordinates in the three coordinate systems correlated well with each other. On the left side, more ventral location of the active contact was associated with greater LED decrease. STN-DBS improves motor function and enables the reduction in antiparkinson medication with an acceptable adverse effect profile. More ventral location of the active contact may allow stronger LED reduction. Further research on the correlation between contact location, clinical outcome, and LED reduction is warranted. © 2018 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.

Validity, sensitivity and specificity of the mentation, behavior and mood subscale of the UPDRS.

PubMed

Holroyd, Suzanne; Currie, Lillian J; Wooten, G Frederick

2008-06-01

The unified Parkinson's disease rating scale (UPDRS) is the most widely used tool to rate the severity and the stage of Parkinson's disease (PD). However, the mentation, behavior and mood (MBM) subscale of the UPDRS has received little investigation regarding its validity and sensitivity. Three items of this subscale were compared to criterion tests to examine validity, sensitivity and specificity. Ninety-seven patients with idiopathic PD were assessed on the UPDRS. Scores on three items of the MBM subscale, intellectual impairment, thought disorder and depression, were compared to criterion tests, the telephone interview for cognition status (TICS), psychiatric assessment for psychosis and the geriatric depression scale (GDS). Non-parametric tests of association were performed to examine concurrent validity of the MBM items. The sensitivities, specificities and optimal cutoff scores for each MBM item were estimated by receiver operating characteristic (ROC) curve analysis. The MBM items demonstrated low to moderate correlation with the criterion tests, and the sensitivity and specificity were not strong. Even using a score of 7.0 on the items of the MBM demonstrated a sensitivity/specificity of only 0.19/0.48 for intellectual impairment, 0.60/0.72 for thought disorder and 0.61/0.87 for depression. Using a more appropriate cutoff of 2.0 revealed sensitivities of 0.01, 0.38 and 0.13 respectively. The MBM subscale items of intellectual impairment, thought disorder and depression are not appropriate for screening or diagnostic purposes. Tools such as the TICS and the GDS should be considered instead.

Quantitative Analysis of Voice in Parkinson Disease Compared to Motor Performance: A Pilot Study.

PubMed

Silbergleit, Alice K; LeWitt, Peter A; Peterson, Edward L; Gardner, Glendon M

2015-01-01

Characteristic features of hypokinetic dysarthria develop in Parkinson disease (PD). We hypothesized that quantified acoustic changes of voice might provide a correlate of disease severity. To determine if there are significant differences in acoustic measures of voice between mild and moderate PD; 2) To evaluate correlations between acoustic parameters of voice and subtests of the UPDRS in mild and moderate PD. Twenty six participants with PD underwent vocal acoustic testing while off PD medication, for comparison to 22 healthy controls. Participants with PD were divided into two groups based upon UPDRS activities of daily living (ADL) ratings: summed scores were used to define mild and moderate PD. Participants voiced /i/ ("ee") at comfort, high, and low pitch (3 trials/pitch). The CSpeech Waveform Analysis Program was used to analyze cycle-to-cycle frequency ("jitter") and amplitude ("shimmer") irregularities of the vocal signal, signal-to-noise ratio, and maximum phonation frequency range converted to semitones. Sections of UPDRS scores were correlated to acoustic variables of voice. Key findings included a significant difference between the semitone range of the control subjects and the moderate PD group (p = 0.036). Further analyses revealed significant differences in semitone range for males between the controls vs. mild PD (p = 0.014), and controls vs. moderate PD (p = 0.005). Significant correlations were also found between acoustic findings and both the ADL and motor portions of the UPDRS. Acoustic analysis of voice, particularly frequency range, may provide a quantifiable correlate of disease progression in PD.

Discordance Between Physician Assessment and Patient-Reported Depressive Symptoms in Parkinson Disease.

PubMed

Lachner, Christian; Armstrong, Melissa J; Gruber-Baldini, Ann L; Rezvani, Zahra; Reich, Stephen G; Fishman, Paul S; Salazar, Richard; Shulman, Lisa M

2017-07-01

To assess concordance between physician assessment and patient-reported symptoms when screening for depression in Parkinson disease (dPD). Depression in Parkinson disease is highly prevalent (∼40%) and has a significant impact on quality of life and disability, yet physician recognition and treatment remain inadequate. One thousand seventy-six patients with PD completed the Brief Symptom Inventory-18 (BSI-18), a screening questionnaire for psychiatric symptoms, which was compared to item #3 (depression) on the Unified Parkinson's Disease Rating Scale (UPDRS). The mean BSI-18 depression score was 51.4 (9.7). Of the 170 (16%) patients screening positive for dPD on the BSI-18, 104 (61%) were not recognized as depressed by neurologists on the UPDRS. Factors associated with lower neurologist recognition included male gender, better mental health quality of life, and lack of antidepressant use. More than 60% of patients screening positive for depression on self-report were not recognized by neurologists on the UPDRS. A patient-reported screening tool for depression may improve recognition and management of dPD.

Pharmacokinetics and effect of food after oral administration of prolonged-release tablets of ropinirole hydrochloride in Japanese patients with Parkinson's disease.

PubMed

Hattori, N; Hasegawa, K; Sakamoto, T

2012-10-01

Ropinirole hydrochloride, a dopamine receptor agonist with a non-ergot alkaloid structure, is highly selective for the dopamine D(2) /D(3) receptors. This study was conducted to evaluate the steady-state pharmacokinetics, safety and efficacy after repeated oral administration of prolonged-release tablets of ropinirole hydrochloride in the absence of L-dopa preparations in Japanese patients with Parkinson's disease (PD). This was a multicenter, open-label, uncontrolled study. The total duration of participation in the study ranged from 56 to 63 weeks. In the study, the plasma concentrations of ropinirole, its major metabolite SK&F104557 (N-depropyl ropinirole) and another metabolite SK&F89124 (ropinirole hydroxylated at the seventh position of the indole ring) were assessed. Safety based on adverse events, haematology, biochemistry, urinalysis and electrocardiography (ECG) (standard 12-lead ECG) were evaluated, and vital signs (blood pressure/pulse rate) were measured. Efficacy based on the Japanese version of Unified Parkinson's Disease Rating Scale (UPDRS) Parts III (motor) and II [activities of daily living (ADL)] as well as tolerability was evaluated. After repeated oral administration of prolonged-release tablets of ropinirole hydrochloride in Japanese patients with PD, ropinirole, SK&F104557 and low levels of SK&F89124 were detected in plasma. The trough concentrations of ropinirole and the two metabolites increased in proportion to the dose when ropinirole hydrochloride prolonged-release tablets were administered at doses ranging from 2 to 16 mg/day. The plasma exposure to ropinirole and its two metabolites after intake of normal diet was comparable to that in the fasting state. The most common adverse events (10% or more) were somnolence, nausea, constipation, hallucination and nasopharyngitis. Most adverse events were mild or moderate in severity, and with no death. During the treatment period, serious adverse events were reported in five patients. Efficacy analysis (LOCF) at the final endpoint up to week 16 demonstrated a mean (SD) change from baseline in the Japanese UPDRS III (motor) and II (ADL) scores of -11·3 (8·21) and -3·9 (3·22), respectively, and thereafter remained at similar levels until week 52. After administration of prolonged-release tablets of ropinirole hydrochloride in the absence of L-dopa preparations in Japanese patients with PD, the plasma pharmacokinetics of ropinirole and its metabolites was linear and not affected by food. Compared with the immediate-release (IR) tablet, the prolonged-release tablet can be administered to Japanese patients with PD at a reduced daily dose frequency and adjusted to the maintenance dose after fewer dose changes with a smaller diurnal variation in the plasma ropinirole concentration. © 2012 Blackwell Publishing Ltd.

Using Cognitive Pretesting in Scale Development for Parkinson’s Disease: The Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Example

PubMed Central

Tilley, Barbara C.; LaPelle, Nancy R.; Goetz, Christopher G.; Stebbins, Glenn T.

2016-01-01

Background Cognitive pretesting, a qualitative step in scale development, precedes field testing and assesses the difficulty of instrument completion for examiners and respondents. Cognitive pretesting assesses respondent interest, attention span, discomfort, and comprehension, and highlights problems with the logical structure of questions/response options that can affect understanding. In the past this approach was not consistently used in the development or revision of movement disorders scales. Methods We applied qualitative cognitive pretesting using testing guides in development of the Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). The guides were based on qualitative techniques, verbal probing and “think-aloud” interviewing, to identify problems with the scale from the patient and rater perspectives. English-speaking Parkinson’s disease patients and movement disorders specialists (raters) from multiple specialty clinics in the United States, Western Europe and Canada used the MDS-UPDRS and completed the testing guides. Results Two rounds of cognitive pretesting were necessary before proceeding to field testing of the revised scale to assess clinimetric properties. Scale revisions based on cognitive pretesting included changes in phrasing, simplification of some questions, and addition of a reassuring statement explaining that not all PD patients experience the symptoms described in the questions. Conclusions The strategy of incorporating cognitive pretesting into scale development and revision provides a model for other movement disorders scales. Cognitive pretesting is being used in translating the MDS-UPDRS into multiple languages to improve comprehension and acceptance and in the development of a new Unified Dyskinesia Rating Scale for Parkinson’s disease patients. PMID:24613868

Educational attainment and motor burden in advanced Parkinson's disease - The emerging role of education in motor reserve.

PubMed

Blume, Josefine; Rothenfusser, Eva; Schlaier, Jürgen; Bogdahn, Ulrich; Lange, Max

2017-10-15

To explore the relationship of motor burden and educational attainment in patients with advanced stage PD. We included 102 consecutive patients who underwent a complete evaluation for DBS surgery, including detailed neuropsychological testing and UPDRSIII in a standardized Levodopa challenge. Years of education (YoE) were calculated as the highest grade attained in secondary school plus years for post-secondary training. The OFF medication UPDRS-III score was associated with YoE (p=0.006; t=-2.82) and age (p=0.007; t=-2.75) in our multivariable linear regression model even while including disease duration (p=0.8; t=0.21), presence of mild cognitive impairment (MCI) (p=0.9; t=0.16) or current IQ (p=0.2; t=1.25) as additional covariables. In a subgroup of 60 patients two years after DBS, the ON/ON UPDRS score was associated with YoE (p=0.01; t=-2.42) and diagnosis of PD dementia (p=0.05, t=1.95), while age (p=0.08, t=1.75), disease duration (p=0.6t=0.48) and LEDD (p=0.3; t=1.05) showed no significant association to ON/ON UPDRS score. We found an inverse correlation between years of education and lower (better) UPDRS -III motor score after adjusting for important covariables. Education may lead to an increased ability to compensate disturbances in basal ganglia circuits affecting not only for cognitive, but also for motor aspects of PD. Thus, educational attainment may play an important role in the concept of motor reserve. Copyright © 2017 Elsevier B.V. All rights reserved.

Efficacy, safety and tolerability of rasagiline as adjunctive therapy in elderly patients with Parkinson's disease.

PubMed

Tolosa, E; Stern, M B

2012-02-01

Rasagiline, an MAO-B inhibitor, is indicated for the treatment of Parkinson's disease (PD). In this post hoc analysis, the efficacy, safety and tolerability of rasagiline as an adjunct to levodopa were compared with placebo in elderly (≥70 years) and younger (<70 years) patients with PD. Data were pooled from the Parkinson's Rasagiline: Efficacy and Safety on the Treatment of 'OFF' and Lasting effect in Adjunct therapy with Rasagiline Given Once daily randomized, double-blind, placebo-controlled trials with the primary efficacy end-point being the reduction from baseline in daily OFF time. Secondary efficacy end-points included scores for Clinical Global Improvement (CGI)-Examiner during ON time, Unified Parkinson's Disease Rating Scale (UPDRS)-ADL during OFF time, UPDRS-Motor during ON time and total daily ON time with and without troublesome dyskinesia. Tolerability was evaluated from adverse events (AEs) in the two age groups. Rasagiline decreased daily OFF time versus placebo (P<0.01) and improved CGI-Examiner score (P=0.001) and UPDRS-Motor ON score (P<0.05). Changes in UPDRS-ADL OFF score and total daily ON time without dyskinesia also favoured rasagiline but were not significant. Between-group comparisons (≥70 vs. <70 years) showed that efficacy was unaffected by age for all end-points (P>0.1), and rasagiline was well tolerated amongst both groups of patients with a comparable incidence of total and dopaminergic AEs (P>0.1). Adjunct rasagiline is efficacious and well tolerated in elderly non-demented patients (≥70 years) with moderate to advanced PD. Confirmation of the efficacy and safety of rasagiline in the elderly patient subgroup is especially relevant because of the increasing number of elderly patients with PD. © 2011 The Author(s). European Journal of Neurology © 2011 EFNS.

Effect of rasagiline as adjunct therapy to levodopa on severity of OFF in Parkinson's disease.

PubMed

Stocchi, F; Rabey, J M

2011-12-01

The LARGO study demonstrated that rasagiline 1 mg/day as adjunct to levodopa significantly reduces OFF time to the same magnitude as adjunct entacapone. This substudy of LARGO aimed to assess the effect of rasagiline and entacapone on the motor symptoms of PD during the practically defined OFF state. LARGO was a randomized, double-blind, multicenter trial that assessed the efficacy and safety of rasagiline (1 mg/day), entacapone (200 mg with each levodopa dose), and placebo in 687 levodopa-treated PD patients with motor fluctuations. A substudy of LARGO measured UPDRS motor scores in the practically defined OFF state in 32 rasagiline, 36 entacapone, and 37 placebo patients. Treatment with rasagiline produced a significant improvement over placebo of 5.64 units in UPDRS motor OFF score (P = 0.013 vs. placebo). By contrast, the effect of adjunct entacapone was not significant (P = 0.14 vs. placebo). Whereas rasagiline also showed a trend in reducing the UPDRS-ADL OFF score (P = 0.058 vs. placebo), no such trend was noted for entacapone (P = 0.26 vs. placebo). Retrospective analysis, using the Bonferroni correction, of UPDRS motor subdomains further revealed that rasagiline, but not entacapone, significantly improved bradykinesia (P < 0.001) and showed trends for improvements in facial expression, speech, and axial impairment during OFF time. This study provides the first objectively measured evidence that adjunct rasagiline 1 mg/day is effective in reducing the severity of motor symptoms in the OFF state. This suggests a continuous effect of rasagiline 1 mg/day throughout the day and night and is consistent with its extended duration of therapeutic action. © 2011 The Author(s). European Journal of Neurology © 2011 EFNS.

Testing objective measures of motor impairment in early Parkinson's disease: Feasibility study of an at-home testing device.

PubMed

Goetz, Christopher G; Stebbins, Glenn T; Wolff, David; DeLeeuw, William; Bronte-Stewart, Helen; Elble, Rodger; Hallett, Mark; Nutt, John; Ramig, Lorraine; Sanger, Terence; Wu, Allan D; Kraus, Peter H; Blasucci, Lucia M; Shamim, Ejaz A; Sethi, Kapil D; Spielman, Jennifer; Kubota, Ken; Grove, Andrew S; Dishman, Eric; Taylor, C Barr

2009-03-15

We tested the feasibility of a computer based at-home testing device (AHTD) in early-stage, unmedicated Parkinson's disease (PD) patients over 6 months. We measured compliance, technical reliability, and patient satisfaction to weekly assessments of tremor, small and large muscle bradykinesia, speech, reaction/movement times, and complex motor control. relative to the UPDRS motor score. The AHTD is a 6.5'' x 10'' computerized assessment battery. Data are stored on a USB memory stick and sent by internet to a central data repository as encrypted data packets. Although not designed or powered to measure change, the study collected data to observe patterns relative to UPDRS motor scores. Fifty-two PD patients enrolled, and 50 completed the 6 month trial, 48 remaining without medication. Patients complied with 90.6% of weekly 30-minute assessments, and 98.5% of data packets were successfully transmitted and decrypted. On a 100-point scale, patient satisfaction with the program at study end was 87.2 (range: 80-100). UPDRS motor scores significantly worsened over 6 months, and trends for worsening over time occurred for alternating finger taps (P = 0.08), tremor (P = 0.06) and speech (P = 0.11). Change in tremor was a significant predictor of change in UPDRS (P = 0.047) and was detected in the first month of the study. This new computer-based technology offers a feasible format for assessing PD-related impairment from home. The high patient compliance and satisfaction suggest the feasibility of its incorporation into larger clinical trials, especially when travel is difficult and early changes or frequent data collection are considered important to document.

Functional improvement after subthalamic stimulation in Parkinson's disease: a non-equivalent controlled study with 12-24 month follow up.

PubMed

Capecci, M; Ricciuti, R A; Burini, D; Bombace, V G; Provinciali, L; Iacoangeli, M; Scerrati, M; Ceravolo, M G

2005-06-01

This study aimed to assess the effectiveness of chronic bilateral STN-S in improving the functional status of PD patients compared with patients treated with drugs alone. Controlled study of disability index changes over 12 and 24 month chronic STN stimulation. Of 39 patients with advanced PD meeting CAPSIT criteria for STN-S, 23 underwent surgery; 16 patients decided against surgery and continued on drug schedule adjustments. Functional status was measured using the Activities of Daily Living section of the Unified Parkinson's Disease Rating Scale (UPDRS-ADL), Brown's Disability Scale, and Functional Independence Measure. UPDRS motor score and subscores for selected items, levodopa equivalent daily dose, and Beck Depression Inventory scores were also monitored. T12 follow up data were available for all 39 patients and T24 data for 13 STN-S and 8 control subjects. Compared with controls, STN-S patients experienced significant or highly significant improvements in all independence measures at both 12 and 24 months (time x treatment effect T12: F = 19.5, p = 0.00008; T24: F = 6.2, p = 0.005). Forward stepwise regression for independent predictors of the yearly rate of UPDRS-ADL score modification in the entire sample showed that treatment was the only factor significantly associated with functional status change (beta coefficient -0.54, t value -2.5, p = 0.02), whereas other variables-UPDRS motor score, BDI, and age at disease onset and enrolment-were not in the equation. STN-S is an effective therapeutic option in advanced PD. It induced a consistent improvement of functional abilities over two years to an extent that was not achieved with drug therapy alone.

TESTING OBJECTIVE MEASURES OF MOTOR IMPAIRMENT IN EARLY PARKINSON’S DISEASE: FEASIBILITY STUDY OF AN AT-HOME TESTING DEVICE

PubMed Central

Goetz, Christopher G.; Stebbins, Glenn T.; Wolff, David; DeLeeuw, William; Bronte-Stewart, Helen; Elble, Rodger; Hallett, Mark; Nutt, John; Ramig, Lorraine; Sanger, Terence; Wu, Allan D.; Kraus, Peter H.; Blasucci, Lucia M.; Shamim, Ejaz A.; Sethi, Kapil D.; Spielman, Jennifer; Kubota, Ken; Grove, Andrew S.; Dishman, Eric; Taylor, C Barr

2014-01-01

We tested the feasibility of a computer based at-home testing device (AHTD) in early-stage, unmedicated Parkinson’s disease (PD) patients over 6 months. We measured compliance, technical reliability, and patient satisfaction to weekly assessments of tremor, small and large muscle bradykinesia, speech, reaction/movement times, and complex motor control. relative to the UPDRS motor score. The AHTD is a 6.5 x 10 computerized assessment battery. Data are stored on a USB memory stick and sent by internet to a central data repository as encrypted data packets. Although not designed or powered to measure change, the study collected data to observe patterns relative to UPDRS motor scores. Fifty-two PD patients enrolled, and 50 completed the six month trial, 48 remaining without medication. Patients complied with 90.6% of weekly 30-minute assessments, and 98.5% of data packets were successfully transmitted and decrypted. On a 100-point scale, patient satisfaction with the program at study end was 87.2 (range 80–100). UPDRS motor scores significantly worsened over 6 months, and trends for worsening over time occurred for alternating finger taps (p=.08), tremor (p=.06) and speech (p=.11). Change in tremor was a significant predictor of change in UPDRS (p=0.047) and was detected in the first month of the study. This new computer-based technology offers a feasible format for assessing PD-related impairment from home. The high patient compliance and satisfaction suggest the feasibility of its incorporation into larger clinical trials, especially when travel is difficult and early changes or frequent data collection are considered important to document. PMID:19086085

A Two Year Randomized Controlled Trial of Progressive Resistance Exercise for Parkinson’s Disease

PubMed Central

Corcos, Daniel M.; Robichaud, Julie A.; David, Fabian J.; Leurgans, Sue E.; Vaillancourt, David E.; Poon, Cynthia; Rafferty, Miriam R.; Kohrt, Wendy M.; Comella, Cynthia L.

2013-01-01

Background The effects of progressive resistance exercise (PRE) on the motor signs of Parkinson’s disease have not been studied in controlled trials. Our aim was to compare 6, 12, 18, and 24 month outcomes of patients with Parkinson’s disease who received PRE to a stretching, balance, and strengthening exercise program. Methods We conducted a randomized controlled trial between September 2007 and July 2011. Pairs of patients, matched by sex and off-medication Unified Parkinson’s Disease Rating Scale, motor subscale (UPDRS-III), were randomly assigned to the interventions with a 1:1 allocation ratio. The PRE group performed a weight lifting program. The Modified Fitness Counts (mFC) group performed a stretching, balance, and strengthening exercise program. Patients exercised two days per week for 24 months at a gym. A personal trainer directed both weekly sessions for the first six months and one weekly session after six months. The primary outcome was the off-medication UPDRS-III score. Patients were followed for 24 months at six-month intervals. Results Of 51 patients, 20 in PRE and 18 in mFC completed the trial. At 24 months, the mean off-medication UPDRS-III score decreased more with PRE than with mFC (mean difference: - 7·3 points; 95% CI: -11·3 to -3·6; P < 0·001). The PRE group had ten adverse events. The mFC group had seven adverse events. Conclusions PRE demonstrated a statistically and clinically significant reduction in UPDRS-III scores compared to mFC and is recommended as a useful adjunct therapy to improve Parkinsonian motor signs. PMID:23536417

Levodopa/carbidopa/entacapone versus levodopa/dopa-decarboxyiase inhibitor for the treatment of Parkinson's disease: systematic review, meta-analysis, and economic evaluation.

PubMed

Yi, Zhan-Miao; Qiu, Ting-Ting; Zhang, Yuan; Liu, Na; Zhai, Suo-Di

2018-01-01

To review the evidence for efficacy, safety, and cost-effectiveness of levodopa/carbidopa/entacapone (LCE) compared with levodopa/dopa-decarboxyiase inhibitor (DDCI) for Parkinson's disease (PD). PubMed, Embase, the Cochrane Library, and Chinese databases WangFang Data, Chinese Sci-tech Journals Database and China National Knowledge Infrastructure, as well as ClinicalTrials.gov, were searched for randomized controlled trials with "levodopa/carbidopa/entacapone" as keywords. The search period was from inception to August 2017. We conducted meta-analyses to synthesize the evidence quantitatively. A total of 5,693 records were obtained. We included seven randomized controlled trials and one cost-effectiveness study after the screening process. Compared with levodopa-DDCI, LCE improved patient Unified Parkinson's Disease Rating Scale (UPDRS) II score (mean difference [MD] -1.17, 95% CI -1.64 to -0.71), UPDRS III score (MD -1.55, 95% CI -2.29 to -0.81), and Schwab and England daily activity rating (MD 2.05, 95% CI 0.85-3.26). There was no statistically significant difference in the risk of serious adverse events (AEs) or discontinuation due to AEs in patients with LCE, and the risk of total AEs was higher in the LCE group (risk ratio [RR] 1.33, 95% CI 1.05-1.70). The incremental cost-effectiveness ratio of LCE was £3,105 per quality-adjusted life-year (QALY) gained in the UK. LCE can improve PD patients' motor symptoms and daily living functioning when compared with levodopa/DDCI.

Rotigotine vs ropinirole in advanced stage Parkinson's disease: a double-blind study.

PubMed

Mizuno, Yoshikuni; Nomoto, Masahiro; Hasegawa, Kazuko; Hattori, Nobutaka; Kondo, Tomoyoshi; Murata, Miho; Takeuchi, Masahiro; Takahashi, Masayoshi; Tomida, Takayuki

2014-12-01

To confirm the superiority of transdermal rotigotine up to 16 mg/24 h over placebo, and non-inferiority to ropinirole, in Japanese Parkinson's disease (PD) patients on concomitant levodopa therapy. This trial was a randomized, double-blind, double-dummy, three-arm parallel group placebo- and ropinirole-controlled trial. Four-hundred and twenty PD patients whose motor symptoms were not well controlled by levodopa treatment were randomized 2:2:1 to receive rotigotine, ropinirole (up to 15 mg/day) or placebo during a 16-week treatment period followed by a 4-week taper period. The primary variable was change in the Unified Parkinson's Disease Rating Scale (UPDRS) Part III (ON state) sum score from baseline to the end of the treatment period. The difference in the change in the UPDRS Part III (ON state) sum score from baseline to the end of treatment between rotigotine and placebo groups was -6.4 ± 1.2 (95% CI: -8.7 to -4.1; p < 0.001), indicating superiority of rotigotine over placebo. The difference between rotigotine and ropinirole groups was -1.4 ± 1.0 (95% CI: -3.2 to 0.5), below the non-inferiority margin, indicating the non-inferiority of rotigotine to ropinirole. Application site reaction was seen in 57.7% of the patients in the rotigotine group and in 18.6% in the ropinirole group (P < 0.001). No other safety issue was noted. Rotigotine was well tolerated at doses up to 16 mg/24 h and showed similar efficacy to ropinirole except that the application site reaction was much higher in the rotigotine group. Copyright © 2014. Published by Elsevier Ltd.

The single-leg-stance test in Parkinson's disease.

PubMed

Chomiak, Taylor; Pereira, Fernando Vieira; Hu, Bin

2015-03-01

Timed single-leg-stance test (SLST) is widely used to assess postural control in the elderly. In Parkinson's disease (PD), it has been shown that an SLST around 10 seconds or below may be a sensitive indicator of future falls. However, despite its role in fall risk, whether SLST times around 10 seconds marks a clinically important stage of disease progression has largely remained unexplored. A cross-sectional study where 27 people with PD were recruited and instructed to undertake timed SLST for both legs was conducted. Disease motor impairment was assessed with the Unified Parkinson's Disease Rating Scale Part 3 (UPDRS-III). This study found that: 1) the SLST in people with PD shows good test-retest reliability; 2) SLST values can be attributed to two non-overlapping clusters: a low (10.4 ± 6.3 seconds) and a high (47.6 ± 11.7 seconds) value SLST group; 3) only the low value SLST group can be considered abnormal when age-matched normative SLST data are taken into account for comparison; and 4) lower UPDRS-III motor performance, and the bradykinesia sub-score in particular, are only associated with the low SLST group. These results lend further support that a low SLST time around 10 seconds marks a clinically important stage of disease progression with significant worsening of postural stability in PD.

The Single-Leg-Stance Test in Parkinson’s Disease

PubMed Central

Chomiak, Taylor; Pereira, Fernando Vieira; Hu, Bin

2015-01-01

Background Timed single-leg-stance test (SLST) is widely used to assess postural control in the elderly. In Parkinson’s disease (PD), it has been shown that an SLST around 10 seconds or below may be a sensitive indicator of future falls. However, despite its role in fall risk, whether SLST times around 10 seconds marks a clinically important stage of disease progression has largely remained unexplored. Methods A cross-sectional study where 27 people with PD were recruited and instructed to undertake timed SLST for both legs was conducted. Disease motor impairment was assessed with the Unified Parkinson’s Disease Rating Scale Part 3 (UPDRS-III). Results This study found that: 1) the SLST in people with PD shows good test-retest reliability; 2) SLST values can be attributed to two non-overlapping clusters: a low (10.4 ± 6.3 seconds) and a high (47.6 ± 11.7 seconds) value SLST group; 3) only the low value SLST group can be considered abnormal when age-matched normative SLST data are taken into account for comparison; and 4) lower UPDRS-III motor performance, and the bradykinesia sub-score in particular, are only associated with the low SLST group. Conclusion These results lend further support that a low SLST time around 10 seconds marks a clinically important stage of disease progression with significant worsening of postural stability in PD. PMID:25584104

Impaired frontal lobe functions in patients with Parkinson's disease and psychosis.

PubMed

Thota, Naveen; Lenka, Abhishek; George, Lija; Hegde, Shantala; Arumugham, Shyam Sundar; Prasad, Shweta; Stezin, Albert; Kamble, Nitish; Yadav, Ravi; Pal, Pramod Kumar

2017-12-01

Patients with Parkinson's disease (PD) may develop several non-motor symptoms (NMS). Psychosis is one of the debilitating NMS of PD. The neurobiology of psychosis is not fully understood. This study aims to compare the frontal lobe functions of PD patients with and without psychosis using the Frontal Assessment Battery (FAB). This study included 69 patients with PD; 34 with psychosis (PD-P) and 35 without psychosis (PD-NP). Mini Mental Status Examination (MMSE) was used to screen for cognitive impairment. Unified Parkinson's disease Rating scale part-III (UPDRS-III) was used to measure the severity and Hoehn and Yahr score (H&Y) was used to measure the stage of PD. Frontal lobe functions were assessed by FAB. The PD-P and PD-NP groups were comparable for age (58.7±8.4 vs 55.7±8.2, p=0.14), age at onset of symptoms (51.4±8.1 vs 50.0±8.8, p=0.48), gender distribution (men: 88%vs 80%, p=0.51), MMSE (28.2±1.9 vs 28.7±1.2 p=0.12), levodopa equivalent dose/day (736.0±376.3 vs 625.2±332.2, p=0.19), UPDRS-III OFF-score (36.7±8.8 vs 35.4±13.2, p=0.64), UPDRS-III ON-score (13.2±5.4 vs 12.4±6.6, p=0.44) and H&Y stage (2.3±0.3 vs 2.3±0.3, p=0.07). PD-P group had lower total FAB score compared to PD-NP group (13.9±2.2 vs 16.5±1.8, p<0.01). On the FAB, PD-P group had lower scores compared to PD-NP in lexical fluency (FAB-2), programming (FAB-3), sensitivity to interference (FAB-4) and inhibitory control (FAB-5). Patients with PD-P had significant frontal lobe dysfunction compared to PD-NP. FAB may be a simple and useful bedside tool to assess frontal dysfunction in patients with PD in a busy neurological set up. Copyright © 2017 Elsevier B.V. All rights reserved.

Symptomatic efficacy of rasagiline monotherapy in early Parkinson's disease: post-hoc analyses from the ADAGIO trial.

PubMed

Jankovic, Joseph; Berkovich, Elijahu; Eyal, Eli; Tolosa, Eduardo

2014-06-01

The ADAGIO study included a large cohort of patients with early PD (baseline total-UPDRS = 20) who were initially randomized to rasagiline and placebo, thereby allowing analyses of symptomatic efficacy. Post-hoc analyses comparing the efficacy of rasagiline 1 mg/day (n = 288) versus placebo (n = 588) on key symptoms at 36 weeks, and on total-UPDRS scores over 72 weeks (completer population: rasagiline 1 mg/day n = 221, placebo n = 392) were performed. Treatment with rasagiline resulted in significantly better tremor, bradykinesia, rigidity and postural-instability-gait-difficulty scores at week 36 versus placebo. Whereas the placebo group experienced progressive deterioration from baseline (2.6 UPDRS points at week 36), patients in the rasagiline group were maintained at baseline values at week 60 (UPDRS-change of 0.3 points). At week 72, patients who had received continuous monotherapy with rasagiline experienced a worsening of only 1.6 points. Treatment with rasagiline maintained motor function to baseline values for at least a year with significant benefits observed in all key PD motor symptoms. Copyright © 2014 Elsevier Ltd. All rights reserved.

A randomized trial of a low-dose Rasagiline and Pramipexole combination (P2B001) in early Parkinson's disease.

PubMed

Olanow, C Warren; Kieburtz, Karl; Leinonen, Mika; Elmer, Lawrence; Giladi, Nir; Hauser, Robert A; Klepiskaya, Olga S; Kreitzman, David L; Lew, Mark F; Russell, David S; Kadosh, Shaul; Litman, Pninit; Friedman, Hadas; Linvah, Nurit; The P B Study Group, For

2017-05-01

Rasagiline and pramipexole act to improve striatal dopaminergic transmission in PD via distinct and potentially synergistic mechanisms. We performed a placebo-controlled study to determine whether 2 doses of a novel slow-release, low-dose combination of rasagiline and pramipexole (P2B001) are effective and have a good safety profile in patients with early untreated PD. Previously untreated patients with early PD were randomized (1:1:1) to once-daily treatment with P2B001 (0.3 mg pramipexole/0.75 mg rasagiline), P2B001 (0.6 mg pramipexole/0.75 mg rasagiline) or placebo in a 12-week multicenter double-blind, placebo-controlled trial. The primary endpoint was the change from baseline to final visit in Total-UPDRS score versus placebo. Secondary measures included responder analyses of patients achieving ≥4 UPDRS point reduction, and changes in Parkinson Disease Quality of Life Scale-39 and UPDRS activities of daily living and motor scores. A total of 149 participants were randomized and 136 (91.3%) completed the study. Adjusted mean change from baseline to final visit versus placebo in Total-UPDRS score was -4.67 ± 1.28 points for the P2B001 0.6/0.75 mg group (P = .0004) and -3.84 ± 1.25 points for the 0.3/0.75 mg group (P = .003). Significant benefits were also observed for both doses in the responder analysis (P = .0002 and P = .0001), Parkinson Disease Quality of Life Scale-39 scores (P = .05 and P = .01), and the UPDRS motor (P = .02 and P = .006) and activities of daily living (P = .005 and P = .0004) subscores. Adverse events of P2B001 were comparable to placebo apart from transient nausea and somnolence, which were more common with P2B001 treatment. P2B001 offers a promising treatment option for patients with early PD with good clinical efficacy and a low risk of adverse events. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

Phase II randomised controlled trial of a 6-month self-managed community exercise programme for people with Parkinson's disease.

PubMed

Collett, Johnny; Franssen, Marloes; Meaney, Andy; Wade, Derick; Izadi, Hooshang; Tims, Martin; Winward, Charlotte; Bogdanovic, Marko; Farmer, Andrew; Dawes, Helen

2017-03-01

Evidence for longer term exercise delivery for people with Parkinson's disease (PwP) is deficient. Evaluate safety and adherence to a minimally supported community exercise intervention and estimate effect sizes (ES). 2-arm parallel phase II randomised controlled trial with blind assessment. PwP able to walk ≥100 m and with no contraindication to exercise were recruited from the Thames valley, UK, and randomised (1:1) to intervention (exercise) or control (handwriting) groups, via a concealed computer-generated list. Groups received a 6-month, twice weekly programme. Exercise was undertaken in community facilities (30 min aerobic and 30 min resistance) and handwriting at home, both were delivered through workbooks with monthly support visits. Primary outcome was a 2 min walk, with motor symptoms (Movement Disorder Society Unified Parkinson's Disease Rating Scale, MDS-UPDRS III), fitness, health and well-being measured. Between December 2011 and August 2013, n=53 (n=54 analysed) were allocated to exercise and n=52 (n=51 analysed) to handwriting. N=37 adhered to the exercise, most attending ≥1 session/week. Aerobic exercise was performed in 99% of attended sessions and resistance in 95%. Attrition and adverse events (AEs) were similar between groups, no serious AEs (n=2 exercise, n=3 handwriting) were related, exercise group-related AEs (n=2) did not discontinue intervention. Largest effects were for motor symptoms (2 min walk ES=0.20 (95% CI -0.44 to 0.45) and MDS-UPDRS III ES=-0.30 (95% CI 0.07 to 0.54)) in favour of exercise over the 12-month follow-up period. Some small effects were observed in fitness and well-being measures (ES>0.1). PwP exercised safely and the possible long-term benefits observed support a substantive evaluation of this community programme. NCT01439022. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Quantitative Susceptibility Mapping in Parkinson's Disease.

PubMed

Langkammer, Christian; Pirpamer, Lukas; Seiler, Stephan; Deistung, Andreas; Schweser, Ferdinand; Franthal, Sebastian; Homayoon, Nina; Katschnig-Winter, Petra; Koegl-Wallner, Mariella; Pendl, Tamara; Stoegerer, Eva Maria; Wenzel, Karoline; Fazekas, Franz; Ropele, Stefan; Reichenbach, Jürgen Rainer; Schmidt, Reinhold; Schwingenschuh, Petra

2016-01-01

Quantitative susceptibility mapping (QSM) and R2* relaxation rate mapping have demonstrated increased iron deposition in the substantia nigra of patients with idiopathic Parkinson's disease (PD). However, the findings in other subcortical deep gray matter nuclei are converse and the sensitivity of QSM and R2* for morphological changes and their relation to clinical measures of disease severity has so far been investigated only sparsely. The local ethics committee approved this study and all subjects gave written informed consent. 66 patients with idiopathic Parkinson's disease and 58 control subjects underwent quantitative MRI at 3T. Susceptibility and R2* maps were reconstructed from a spoiled multi-echo 3D gradient echo sequence. Mean susceptibilities and R2* rates were measured in subcortical deep gray matter nuclei and compared between patients with PD and controls as well as related to clinical variables. Compared to control subjects, patients with PD had increased R2* values in the substantia nigra. QSM also showed higher susceptibilities in patients with PD in substantia nigra, in the nucleus ruber, thalamus, and globus pallidus. Magnetic susceptibility of several of these structures was correlated with the levodopa-equivalent daily dose (LEDD) and clinical markers of motor and non-motor disease severity (total MDS-UPDRS, MDS-UPDRS-I and II). Disease severity as assessed by the Hoehn & Yahr scale was correlated with magnetic susceptibility in the substantia nigra. The established finding of higher R2* rates in the substantia nigra was extended by QSM showing superior sensitivity for PD-related tissue changes in nigrostriatal dopaminergic pathways. QSM additionally reflected the levodopa-dosage and disease severity. These results suggest a more widespread pathologic involvement and QSM as a novel means for its investigation, more sensitive than current MRI techniques.

Association of CHRNA4 gene rs1044396 and rs1044397 polymorphisms with Parkinson's disease symptoms and smoking.

PubMed

Zhang, L M; Zhang, X P; Chen, Y Q; Ye, W

2015-05-12

We assessed the CHRNA4 exon 5 rs1044396 and rs1044397 polymorphisms and investigated their relationship with Parkinson's disease (PD) severity and several non-motor symptoms. Ninety-seven patients with primary PD and 108 controls were recruited, and their smoking history identified. Patients with PD were assessed using the unified PD rating scale (UPDRS), Hoehn & Yahr (H&Y) grade, Hamilton depression rating scale (HAMD), visual analogue 10-points scale (VAS), and the Pittsburgh sleep quality index (PSQI). Polymerase chain reaction amplification and direct sequencing was performed on genomic DNA to identify polymorphic variants. Statistical analysis demonstrated that there were no gender differences in rs1044396(C→T) and rs1044397(G→A) frequencies. More smokers were identified among carriers of rs1044396 CT/TT genotypes. We also found no differences between PD and control groups in frequencies of either polymorphism. However, in women, PD onset was latest in rs1044397 GA/AA (P = 0.015). rs1044396 CT/TT genotype carriers and rs1044397 GG genotype patients with PD had higher VAS scores. No differences were found on the course of PD, H&Y grade, or UPDRS-II or -III scores between various genotypes, nor were differences found on scores of HAMD, nocturia, or PSQI in PD patients. Our results suggested that the CHRNA4 rs1044396 CT/TT genotype is related to cigarette smoking, that the rs1044397 polymorphism may associate with PD age of onset in women, and that rs1044396 and rs1044397 may relate to pain in PD patients, but not to the course or severity of disease, or to depression or nocturnal or sleeping disorders.

Self-reported dysphagia and its correlates within a prevalent population of people with Parkinson's disease.

PubMed

Walker, Richard W; Dunn, Janet R; Gray, William K

2011-03-01

Many people with Parkinson's disease (PD) experience dysphagia; however, the prevalence of dysphagia in people with PD is unknown. We studied a prevalent population of PD cases. All of those who consented to participate were assessed for anxiety, depression, cognitive function, and quality of life using standard rating scales. Anyone who answered "yes" to either one of the two questions: Do you have difficulty swallowing food/liquid or tablets? and Do you cough after eating/drinking? was considered to have dysphagia. Question 7 of the Unified Parkinson's Disease Rating Scale (UPDRS) was also used to identify dysphagia. Of 106 prevalent PD cases, 75 (38 males) patients consented to examination and assessment. The prevalence of dysphagia was 32.0% (n=24; 11 males). Using the response to UPDRS Question 7 as an indicator of the impact of swallowing problems on the patient, there were significant correlations with cognitive function, anxiety, depression, quality of life, and UPDRS-reported gait disturbance, postural instability and problems with falling. There was no correlation with disease duration, age, or gender. Almost one third of the participants reported dysphagia. There was a strong correlation between dysphagia and gross motor skills; patients reporting such problems should be screened for swallowing problems. © Springer Science+Business Media, LLC 2010

Sarizotan as a treatment for dyskinesias in Parkinson's disease: a double-blind placebo-controlled trial.

PubMed

Goetz, Christopher G; Damier, Philippe; Hicking, Christine; Laska, Eugene; Müller, Thomas; Olanow, C Warren; Rascol, Olivier; Russ, Hermann

2007-01-15

The objective of this study is to conduct a dose-finding study of sarizotan in Parkinson's disease (PD) patients with dyskinesia to identify a safe dose and to identify a sensitive dyskinesia rating measure. Sarizotan is a novel compound with full 5-HT(1A) agonist properties and additional high affinity for D(3) and D(4) receptors. An open label study documented improvements in PD patients with levodopa-induced dyskinesia. There is no precedent for study designs or outcome measures in pivotal trials of antidyskinesia therapies. The approach used here was a multicenter, randomized, placebo-controlled, double-blind, parallel study. Included were PD patients optimized to levodopa and dopaminergic drugs with moderately disabling dyskinesias present greater than or equal to 25% of the waking day. Interventions included sarizotan 2, 4, or 10 mg/day or matching placebo, given in two doses. There were two outcome measures: the primary measure was change from baseline in diary-based on time without dyskinesia; the secondary measures were change from baseline in scores on the Abnormal Involuntary Movement Scale (AIMS), the composite score of Unified Parkinson's Disease Rating Scale (UPDRS) Items 32+33 (dyskinesia duration and disability) and total UPDRS. A total of 398 subjects were randomized, with 381 included in the intention-to-treat population. No significant changes occurred on sarizotan compared to placebo on any diary-based measure of dyskinesia or the AIMS score. The composite score of UPDRS Items 32+33 was significantly improved with 2 mg/day sarizotan, with a trend at 10 mg/day. Adverse events were not significantly different in sarizotan- and placebo-treated patients, but off time significantly increased with sarizotan 10 mg/day. Sarizotan 2 mg/day is a safe agent in PD patients with dyskinesia. To test its role in abating dyskinesia, future studies should focus on this dose and will use the composite score of UPDRS Items 32+33 as the primary outcome. (c) 2006 Movement Disorder Society.

[Clinical trial on treatment of Parkinson's disease of Gan-Shen yin deficiency type by recipe for nourishing Gan-Shen].

PubMed

Zhao, Hong; Li, Wen-Wei; Gao, Jun-Peng

2007-09-01

To observe the curative effect of the recipe for nourishing Gan-Shen on Parkinson's disease (PD) of Gan-Shen yin deficiency type. One hundred and twenty-one PD patients were ran-domly assigned by blocking design to the control group and the treated group in the ratio of 1:1. All were treated according to the international medication guiding principle for PD treatment, but the treated group was ad-ministered with the recipe for nourishing Gan-Shen additionally. The treatment course lasted for 12 consecutive months, and the end point was the end of the 12th month. The unified Parkinson's disease rating scale (UP-DRS) score, TCM primary and secondary symptom scores were evaluated before treatment, every 3 months of treatment and at the end point. The average daily levodopa dose and the Hoehn & Yahr grading were assessed before treatment and at the end point. After treatment, UPDRS score in both groups showed an ascending trend at a slower rate in the treated groups than in the control group. At the 9th and 12th month of medication, a significant difference was found in UPDRS score between the two groups (P < 0.05), and the TCM symptom score was obviously lower in the treated group than in the control group (P < 0.05). At the end point of the trial, the average daily levodopa dose used was lower in the treated group than in the control group (P < 0.05) and there was no significant difference in the Hoehn & Yahr score between the two groups (P > 0.05). The recipe for norishing Gan-Shen can slow the ascending trend of UPDRS score in the PD patients, improve the symptoms of Gan-Shen yin deficiency, and decrease the daily levodopa dose used, showing a curative effect on PD of Gan-Shen yin deficiency type.

Bee Venom for the Treatment of Parkinson Disease - A Randomized Controlled Clinical Trial.

PubMed

Hartmann, Andreas; Müllner, Julia; Meier, Niklaus; Hesekamp, Helke; van Meerbeeck, Priscilla; Habert, Marie-Odile; Kas, Aurélie; Tanguy, Marie-Laure; Mazmanian, Merry; Oya, Hervé; Abuaf, Nissen; Gaouar, Hafida; Salhi, Sabrina; Charbonnier-Beaupel, Fanny; Fievet, Marie-Hélène; Galanaud, Damien; Arguillere, Sophie; Roze, Emmanuel; Degos, Bertrand; Grabli, David; Lacomblez, Lucette; Hubsch, Cécile; Vidailhet, Marie; Bonnet, Anne-Marie; Corvol, Jean-Christophe; Schüpbach, Michael

2016-01-01

In the present study, we examined the potential symptomatic and/or disease-modifying effects of monthly bee venom injections compared to placebo in moderatly affected Parkinson disease patients. We conducted a prospective, randomized double-blind study in 40 Parkinson disease patients at Hoehn & Yahr stages 1.5 to 3 who were either assigned to monthly bee venom injections or equivalent volumes of saline (treatment/placebo group: n = 20/20). The primary objective of this study was to assess a potential symptomatic effect of s.c. bee venom injections (100 μg) compared to placebo 11 months after initiation of therapy on United Parkinson’s Disease Rating Scale (UPDRS) III scores in the « off » condition pre-and post-injection at a 60 minute interval. Secondary objectives included the evolution of UPDRS III scores over the study period and [123I]-FP-CIT scans to evaluate disease progression. Finally, safety was assessed by monitoring specific IgE against bee venom and skin tests when necessary. After an 11 month period of monthly administration, bee venom did not significantly decrease UPDRS III scores in the « off » condition. Also, UPDRS III scores over the study course, and nuclear imaging, did not differ significantly between treatment groups. Four patients were excluded during the trial due to positive skin tests but no systemic allergic reaction was recorded. After an initial increase, specific IgE against bee venom decreased in all patients completing the trial. This study did not evidence any clear symptomatic or disease-modifying effects of monthly bee venom injections over an 11 month period compared to placebo using a standard bee venom allergy desensitization protocol in Parkinson disease patients. However, bee venom administration appeared safe in non-allergic subjects. Thus, we suggest that higher administration frequency and possibly higher individual doses of bee venom may reveal its potency in treating Parkinson disease. ClinicalTrials.gov NCT01341431.

Bee Venom for the Treatment of Parkinson Disease – A Randomized Controlled Clinical Trial

PubMed Central

Hartmann, Andreas; Müllner, Julia; Meier, Niklaus; Hesekamp, Helke; van Meerbeeck, Priscilla; Habert, Marie-Odile; Kas, Aurélie; Tanguy, Marie-Laure; Mazmanian, Merry; Oya, Hervé; Abuaf, Nissen; Gaouar, Hafida; Salhi, Sabrina; Charbonnier-Beaupel, Fanny; Fievet, Marie-Hélène; Galanaud, Damien; Arguillere, Sophie; Roze, Emmanuel; Degos, Bertrand; Grabli, David; Lacomblez, Lucette; Hubsch, Cécile; Vidailhet, Marie; Bonnet, Anne-Marie

2016-01-01

In the present study, we examined the potential symptomatic and/or disease-modifying effects of monthly bee venom injections compared to placebo in moderatly affected Parkinson disease patients. We conducted a prospective, randomized double-blind study in 40 Parkinson disease patients at Hoehn & Yahr stages 1.5 to 3 who were either assigned to monthly bee venom injections or equivalent volumes of saline (treatment/placebo group: n = 20/20). The primary objective of this study was to assess a potential symptomatic effect of s.c. bee venom injections (100 μg) compared to placebo 11 months after initiation of therapy on United Parkinson’s Disease Rating Scale (UPDRS) III scores in the « off » condition pre-and post-injection at a 60 minute interval. Secondary objectives included the evolution of UPDRS III scores over the study period and [123I]-FP-CIT scans to evaluate disease progression. Finally, safety was assessed by monitoring specific IgE against bee venom and skin tests when necessary. After an 11 month period of monthly administration, bee venom did not significantly decrease UPDRS III scores in the « off » condition. Also, UPDRS III scores over the study course, and nuclear imaging, did not differ significantly between treatment groups. Four patients were excluded during the trial due to positive skin tests but no systemic allergic reaction was recorded. After an initial increase, specific IgE against bee venom decreased in all patients completing the trial. This study did not evidence any clear symptomatic or disease-modifying effects of monthly bee venom injections over an 11 month period compared to placebo using a standard bee venom allergy desensitization protocol in Parkinson disease patients. However, bee venom administration appeared safe in non-allergic subjects. Thus, we suggest that higher administration frequency and possibly higher individual doses of bee venom may reveal its potency in treating Parkinson disease. Trial Registration ClinicalTrials.gov NCT01341431 PMID:27403743

Impact of sleep quality on the quality of life of patients with Parkinson's disease: a questionnaire based study.

PubMed

Pandey, Shweta; Bajaj, Bhupender Kumar; Wadhwa, Ankur; Anand, Kuljeet Singh

2016-09-01

Poor sleep quality contributes to the inferior quality of life of patients with Parkinson's disease (PD) despite appropriate treatment of motor symptoms. The literature about the impact of sleep quality on quality of life of patients with PD is as yet sparse. One hundred patients of PD diagnosed as per UK Brain Bank criteria were assessed for severity and stage of PD using UPDRS and modified Hoehn &Yahr scales. The quality of sleep was assessed by Pittsburgh Sleep Quality Index and excessive daytime somnolence (EDS) was evaluated using Epworth Sleepiness Scale. Parkinson's Disease Questionnaire -39 (PDQ-39) was used to determine quality of life of the patients. Comorbid depression and anxiety were assessed using Inventory of Depressive Symptoms-Self Rated and Hamilton Anxiety Rating Scale. Pearson's correlation and multiple linear regressions were used to analyze relation of sleep quality with quality of life of patients. Fifty patients had poor sleep quality. EDS was present in only 9 patients. Co-morbid depression and anxiety were present in 52 and 34 patients respectively. While the motor severity assessed by UPDRS-III was observed to adversely affect quality of life, it did not negatively impact quality of sleep. Higher score on UPDRS-total and UPDRS IV suggesting advanced disease correlated with poor sleep quality. Depression and anxiety were significantly more frequent in patients with poor sleep quality (p<0.01). Patients with poor sleep quality had worse quality of life (r=0.338, p<0.05). Depression and anxiety were also observed to have significant negative impact on quality of life of PD patients (p<0.01). Poor sleep quality was not found to be an independent predictor of quality of life using multiple linear regression analysis. Poor sleep quality along with comorbid depression, anxiety and advanced stage of disease is associated with poor quality of life. Copyright © 2016 Elsevier B.V. All rights reserved.

Remote Traumatic Brain Injury Is Associated with Motor Dysfunction in Older Military Veterans.

PubMed

Gardner, Raquel C; Peltz, Carrie B; Kenney, Kimbra; Covinsky, Kenneth E; Diaz-Arrastia, Ramon; Yaffe, Kristine

2017-09-01

Traumatic brain injury (TBI) has been identified as a risk factor for Parkinson's disease (PD). Motor dysfunction among TBI-exposed elders without PD has not been well characterized. We sought to determine whether remote TBI is a risk factor for motor dysfunction on exam and functionally relevant motor dysfunction in day-to-day life among independently living elders without PD. This is a cross-sectional cohort study of independently living retired military veterans aged 50 or older with (n = 78) and without (n = 85) prior TBI-all without diagnosed PD. To characterize multidimensional aspects of motor function on exam, the Unified Parkinson's Disease Rating Scale (UPDRS) Motor Examination was performed by a board-certified neurologist and used to calculate a modified UPDRS (mUPDRS) global motor score and four domain scores (tremor, rigidity, bradykinesia, and posture/gait). Functionally relevant motor dysfunction was assessed via self-report of falls within the past year. In analyses adjusted for demographics and comorbidities that differed between groups, compared with veterans without TBI, those with moderate-to-severe TBI were more likely to have fallen in past year (33% vs. 14%, risk ratio 2.5 [95% confidence interval 1.1-5.4]), had higher (worse) mUPDRS global motor (p = .03) and posture/gait scores (p = .02), but not higher tremor (p = .70), rigidity (p = .21), or bradykinesia scores (p = .22). Mild TBI was not associated with worse motor function. Remote moderate-to-severe TBI is a risk factor for motor dysfunction-defined as recent falls and impaired posture/gait-among older veterans. TBI-exposed older adults may be ideal candidates for aggressive fall-screening and prevention strategies. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Subthalamic Nucleus Deep Brain Stimulation for Parkinson Disease in Hong Kong: A Prospective Territory-Wide 2-Year Follow-Up Study.

PubMed

Chan, Danny T M; Zhu, Cannon X L; Lau, Claire K Y; Poon, Tak L; Cheung, Fung C; Lee, Michael; Taw, Benedict; Hung, Kwan N; Choi, Priscilla; AuYeung, Mandy; Chan, Germaine; Cheung, Yuk F; Chan, Anne Y Y; Yeung, Jonas H M; Mok, Vincent C T; Poon, Wai S

2016-09-01

We assessed the effects of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with Parkinson disease at the 1-year and 2-year follow-up evaluations. Unified Parkinson's Disease Rating Scale (UPDRS) motor score at "off" medication ("on" DBS) and quality-of-life assessments (39-item Parkinson's Disease Questionnaire [PDQ-39]) were conducted. The percentage of awake "on" time and awake "off" time and levodopa requirement were also assessed. A 2-year prospective study was conducted of 25 consecutive patients from 3 DBS referral centers in Hong Kong. The patients were treated with bilateral stimulation of the STN. Assessments were performed at 1 year and 2 years after DBS and were compared with the baseline. The 2-year outcome assessments were completed by 18 patients. The mean UPDRS motor score improvement was 57% in the first year and 45% in the second year. PDQ-39 showed significant improvement in quality of life for 2 consecutive years. The levodopa requirement decreased 63% in the first year and 55.9% in the second year. The awake "on" time was doubled in the first year and sustained in the second year. Awake "off" time was reduced from 28.1% to 5.9% in the first year and returned to 10.6% in the second year. Improvement of UPDRS motor score, reduction in awake "off" time, and decrease of daily levodopa dosage all were main factors correlated with the improvement in PDQ-39 summary index. The effects of STN DBS in patients with Parkinson disease in Hong Kong were satisfactory. The results showed that reduction in UPDRS motor score, awake "off"-time, and daily levodopa dosage were the major drivers of overall improvement in PDQ-39. Copyright © 2016 Elsevier Inc. All rights reserved.

Low-dose levodopa therapy in Japanese patients with Parkinson's disease: a retrospective study.

PubMed

Kitagawa, Mayumi; Tashiro, Kunio

2005-09-01

To investigate the efficacy and the rate of adverse events of chronic low-dose levodopa-carbidopa therapy in Japanese patients with Parkinson's disease (PD). A total of 92 Japanese PD patients treated with low doses of levodopa from the outset were studied. Both disease-specific motor disabilities and quality of life (QOL) in the patients were evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) and the Parkinson's Disease 39 Quality of Life Questionnaire (PDQ39), respectively. In the overall patient group, the mean duration of treatment, the mean daily dose of levodopa, the disability scores and the motor scores of UPDRS were 6.2 years, 186.4 mg, 8.0 and 19.2, respectively. The rates of motor fluctuations, dyskinesias and hallucinations were 8.7%, 6.5% and 14.1%, respectively. The mean summary index of PDQ39 scores was 23.1. Patients with motor fluctuations showed a significantly earlier disease onset. Dose of levodopa, age at onset, and treatment duration were not associated with the occurrence of dyskinesias. Patients with hallucination had higher doses of levodopa and dopamine agonist. Our results demonstrate that chronic administration of a low-dose levodopa preparation can provide satisfactory benefit with a low incidence of motor complications, and can result in good QOL in Japanese patients with PD. The concomitant use of a small amount of dopamine agonist and amantadine from the outset has partly contributed to a reduced dose of levodopa and the lesser occurrence of motor complications.

Can Dual Task Walking Improve in Parkinson's Disease After External Focus of Attention Exercise? A Single Blind Randomized Controlled Trial.

PubMed

Beck, Eric N; Intzandt, Brittany N; Almeida, Quincy J

2018-01-01

It may be possible to use attention-based exercise to decrease demands associated with walking in Parkinson's disease (PD), and thus improve dual task walking ability. For example, an external focus of attention (focusing on the effect of an action on the environment) may recruit automatic control processes degenerated in PD, whereas an internal focus (limb movement) may recruit conscious (nonautomatic) control processes. Thus, we aimed to investigate how externally and internally focused exercise influences dual task walking and symptom severity in PD. Forty-seven participants with PD were randomized to either an Externally (n = 24) or Internally (n = 23) focused group and completed 33 one-hour attention-based exercise sessions over 11 weeks. In addition, 16 participants were part of a control group. Before, after, and 8 weeks following the program (pre/post/washout), gait patterns were measured during single and dual task walking (digit-monitoring task, ie, walking while counting numbers announced by an audio-track), and symptom severity (UPDRS-III) was assessed ON and OFF dopamine replacement. Pairwise comparisons (95% confidence intervals [CIs]) and repeated-measures analyses of variance were conducted. Pre to post: Dual task step time decreased in the external group (Δ = 0.02 seconds, CI 0.01-0.04). Dual task step length (Δ = 2.3 cm, CI 0.86-3.75) and velocity (Δ = 4.5 cm/s, CI 0.59-8.48) decreased (became worse) in the internal group. UPDRS-III scores (ON and OFF) decreased (improved) in only the External group. Pre to washout: Dual task step time ( P = .005) and percentage in double support ( P = .014) significantly decreased (improved) in both exercise groups, although only the internal group increased error on the secondary counting task (ie, more errors monitoring numbers). UPDRS-III scores in both exercise groups significantly decreased ( P = .001). Since dual task walking improvements were found immediately, and 8 weeks after the cessation of an externally focused exercise program, we conclude that externally focused exercise may improve on functioning of automatic control networks in PD. Internally focused exercise hindered dual tasking ability. Overall, externally focused exercise led to greater rehabilitation benefits in dual tasking and motor symptoms compared with internally focused exercise.

Levodopa Reduces the Phase lag Index of Parkinson's Disease Patients: A Magnetoencephalographic Study.

PubMed

Cao, Chunyan; Li, Dianyou; Zeng, Ke; Zhan, Shikun; Huang, Peng; Li, Xiaoli; Sun, Bomin

2018-06-01

As a method of measuring the phase difference between 2 signals, the phase lag index (PLI) of the alpha and beta bands in patients with Parkinson's disease (PD) was investigated by using magnetoencephalography (MEG). Eighteen PD patients were measured by MEG in the state of overnight withdrawal of levodopa and after levodopa treatment; meanwhile, Unified Parkinson's Disease Rating Scale (UPDRS) III scale was evaluated. Compared with healthy controls, alpha (8-13 Hz) PLI in the frontal and parietal areas elevated in PD patients, while the elevation was reversed by the levodopa treatment. The alterations of the UPDRS III total scale ( r s = 0.552, P = .013, n = 16) and the changes of akinesia scale ( r s = 0.622, P = .005, n = 16) were correlated to the change of beta (13-30 Hz) PLI in the left parietal area. The change of the UPDRS total scale was negatively correlated to duration of disease ( r s = 0.432, P = .047, n = 16). There was a negative correlation between the age of PD patients and the change of alpha PLI in the left frontal area ( r s = 0.519, P = .020, n = 16). PD patients showed a higher mu PLI in the sensorimotor area relative to the healthy controls. The improvement of motor symptoms of PD patients by levodopa was correlated to the inhibition of beta PLI in the sensorimotor area.

Effects of neurostimulation for advanced Parkinson’s disease patients on motor symptoms: A multiple-treatments meta-analysas of randomized controlled trials

PubMed Central

Xie, Cheng-Long; Shao, Bei; Chen, Jie; Zhou, Yi; Lin, Shi-Yi; Wang, Wen-Wen

2016-01-01

Deep brain stimulation (DBS) is the surgical procedure of choice for patients with advanced Parkinson disease (PD). We aim to evaluate the efficacy of GPi (globus pallidus internus), STN (subthalamic nucleus)-DBS and medical therapy for PD. We conducted a systematic review and multiple-treatments meta-analysis to investigate the efficacy of neurostimulation and medical therapy for PD patients. Sixteen eligible studies were included in this analysis. We pooled the whole data and found obvious difference between GPi-DBS versus medical therapy and STN-DBS versus medical therapy in terms of UPDRS scores (Unified Parkinson’s Disease Rating Scale). Meanwhile, we found GPi-DBS had the similar efficacy on the UPDRS scores when compared with STN-DBS. What is more, quality of life, measured by PDQ-39 (Parkinson’s disease Questionnaire) showed greater improvement after GPi-DBS than STN-DBS. Five studies showed STN-DBS was more effective for reduction in medication than GPi-DBS. Overall, either GPi-DBS or STN-DBS was an effective technique to control PD patients’ symptoms and improved their functionality and quality of life. Meanwhile, the UPDRS scores measuring parkinsonian symptoms revealed no significant difference between GPi-DBS and STN-DBS. STN-DBS was more effective for reduction in medication than GPi-DBS. Alternatively, GPi-DBS was more effective for improving the PDQ-39 score than STN-DBS. PMID:27142183

Association between olfactory identification and parkinsonism in patients with non-affective psychosis.

PubMed

Meijer, Julia H; van Harten, Peter; Meijer, Carin J; Koeter, Maarten W; Bruggeman, Richard; Cahn, Wiepke; Kahn, René S; de Haan, L

2016-10-01

Olfactory identification deficits (OIDs) are seen in schizophrenia patients and individuals at increased risk for psychosis but its pathophysiology remains unclear. Although dopaminergic imbalance is known to lie at the core of schizophrenia symptomatology, its role in the development of OIDs has not been elucidated yet. This study investigated the association between OIDs and symptoms of parkinsonism as a derivative of dopaminergic functioning. In 320 patients diagnosed with non-affective psychosis, olfactory identification performance was assessed by means of the Sniffin' Sticks task. Level of parkinsonian symptoms was assessed by means of the Unified Parkinson's Disease Rating Scale (UPDRS-III). By means of multiple linear regression with bootstrapping, the association between UPDRS and Sniffin' Sticks score was investigated while correcting for potential confounders. A Bonferroni corrected P-value of 0.007 was used. Higher UPDRS scores significantly predicted worse olfactory identification in patients with non-affective psychosis with an unadjusted b = -0.07 (95% CI -0.10 to -0.04) and an adjusted b = -0.04 (95% CI -0.07 to -0.01). Results provide preliminary evidence that the same vulnerability may underlie the development of parkinsonism and OIDs in patients with non-affective psychosis. Further investigation should evaluate the clinical value of OIDs as a marker of dopaminergic vulnerability that may predict psychosis. © 2014 Wiley Publishing Asia Pty Ltd.

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

PubMed Central

Borgohain, Rupam; Szasz, J; Stanzione, P; Meshram, C; Bhatt, M; Chirilineau, D; Stocchi, F; Lucini, V; Giuliani, R; Forrest, E; Rice, P; Anand, R

2014-01-01

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. PMID:24323641

Affective symptoms in multiple system atrophy and Parkinson's disease: response to levodopa therapy

PubMed Central

Fetoni, V; Soliveri, P; Monza, D; Testa, D; Girotti, F

1999-01-01

The objective was to determine the extent to which psychiatric disturbances (especially mood disorders) generally considered poor prognostic factors, are present in patients with striatonigral (SND) type multiple system atrophy (MSA) compared with patients with idiopathic Parkinson's disease (IPD).
The Hamilton depression scale (HAM-D), brief psychiatric rating scale (BPRS), and Unified Parkinson's disease rating scale (UPDRS) were administered to clinically probable non-demented patients with SND-type MSA and patients with IPD matched for age and motor disability, at baseline and after receiving levodopa.
At baseline total HAM-D score was greater in patients with IPD. Overall, BPRS score did not differ between the two groups; however, patients with IPD scored higher on anxiety items of the BPRS, and patients with MSA had higher scores on the item indicating blunted affect. After levodopa, both groups improved significantly in UPDRS and HAM-D total scores (just significant for patients with MSA). Patients with IPD improved significantly in total BPRS score but patients with MSA did not.
At baseline patients with IPD were more depressed and anxious than patients with MSA who, by contrast, showed blunted affect. After levodopa, depression and anxiety of patients with IPD improved significantly whereas the affective detachment of patients with MSA did not change. Major neuronal loss in the caudate and ventral striatum, which are part of the lateral orbitofrontal and limbic circuits, may be responsible for the blunted affect not responsive to levodopa therapy found in patients with MSA.

 PMID:10201434

Apathy in patients with Parkinson disease without dementia or depression: a PET study.

PubMed

Robert, Gabriel; Le Jeune, Florence; Lozachmeur, Clément; Drapier, Sophie; Dondaine, Thibault; Péron, Julie; Travers, David; Sauleau, Paul; Millet, Bruno; Vérin, Marc; Drapier, Dominique

2012-09-11

We sought to identify apathy metabolic bases in Parkinson disease (PD). A total of 45 patients with PD who were not clinically depressed (Montgomery-Åsberg Depression Rating Scale [MADRS] <21) and had no dementia (Mattis Dementia Rating Scale [MDRS] >130) were assessed with the Apathy Evaluation Scale (AES) and underwent a resting-state F-18 fluorodeoxyglucose PET (FDG-PET) scan. A motor assessment comprising the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) was conducted and total levodopa equivalent daily dose (LEDD) was calculated. Imaging data were analyzed with statistical parametric mapping. Age, LEDD, and MDRS scores were introduced as covariates. Positive correlations were observed between the AES score and cerebral metabolism in the right inferior frontal gyrus (Brodmann area [BA] 47), right middle frontal gyrus (BA 10), right cuneus (BA 18), and right anterior insula (BA 13). Negative correlations were observed between the AES score and cerebellar metabolism in the semilunar lobules bilaterally, within the posterior lobe. Using an AES score equal to or above 42 to define clinical apathy, prevalence in our patient group was 17.8%. The AES score was negatively correlated with the MDRS score and positively correlated with the "retardation" subscore of the MADRS. It was not correlated with either UPDRS III or LEDD. Results indicate that the frontal, temporal, and cerebellar areas known to be involved in reward, emotion, and cognition are also implicated in apathy in patients with PD without dementia or depression. Their roles in the etiopathology of apathy are discussed.

Impact of Frontal Lobe Function and Behavioral Changes on Health-Related Quality of Life in Patients with Parkinson's Disease: A Cross-Sectional Study from Southwest China.

PubMed

Guo, Xiaoyan; Song, Wei; Chen, Ke; Chen, Xueping; Zheng, Zhenzhen; Cao, Bei; Huang, Rui; Zhao, Bi; Wu, Ying; Shang, Hui-Fang

2015-01-01

Cognitive impairment may negatively impact the health-related quality of life (HRQoL) in patients with Parkinson's disease (PD). However, information on the effects of frontal lobe function and behavior changes on the HRQoL of the Chinese PD population is limited. Studies on the associations among frontal lobe function, behavioral changes and the HRQoL may help optimize the treatment and improve the HRQoL of PD patients. A total of 309 PD patients were evaluated using the Frontal Assessment Battery, the Frontal Behavioral Inventory (FBI) and the PD Questionnaire 39-item version (PDQ-39). Patients with worse frontal lobe function were older (p < 0.001), had longer disease durations (p = 0.002), higher Unified Parkinson's Disease Rating Scale part III (UPDRS-III) scores (p < 0.001) and higher Hoehn and Yahr (H-Y) stages (p = 0.001), and exhibited significantly higher PDQ-39 summary index (SI; p = 0.001) compared with those who had better frontal lobe function. In addition, the disease duration (p = 0.008), UPDRS-III scores (p < 0.001), H-Y stage (p < 0.001), PDQ-39 SI and scores for each domain of the PDQ-39 (p < 0.001) were higher as the severity of frontal behavioral changes increased. The total FBI score (p < 0.001) was positively correlated with the PDQ-39 SI. Frontal behavioral changes were closely associated with poor HRQoL in Chinese PD patients. © 2015 S. Karger AG, Basel.

Effects of rasagiline on freezing of gait in Parkinson's disease - an open-label, multicenter study.

PubMed

Cibulcik, Frantisek; Benetin, Jan; Kurca, Egon; Grofik, Milan; Dvorak, Miloslav; Richter, Denis; Donath, Vladimir; Kothaj, Jan; Minar, Michal; Valkovic, Peter

2016-12-01

Freezing of gait is a disabling symptom in advanced Parkinson's disease. Positive effects have been suggested with MAO-B inhibitors. We report on an open label clinical study on the efficacy of rasagiline as add-on therapy on freezing of gait and quality of life in patients with Parkinson's disease. Forty two patients with freezing of gait were treated with 1 mg rasagiline daily as an add-on therapy. Patients were assessed at baseline and after 1, 2 and 3 months of treatment. Freezing of gait severity was assessed using the Freezing of Gait Questionnaire, motor impairment by the modified MDS UPDRS part III, and quality of life using the PDQ-39 questionnaire. Patients treated with rasagiline had a statistically significant decrease in FoG-Q score and modified MDS UPDRS score after 1, 2 and 3 months of therapy. A moderately strong (r = 0.686, P = 0.002) correlation between the effects on mobility and freezing of gait was found. We also observed a statistically significant improvement in global QoL and in the subscales mobility, ADL, stigma and bodily discomfort in patients after 3 months of rasagiline therapy. A significant correlation (r = 0.570, P = 0.02) between baseline FoG-Q score and the baseline score for the PDQ Mobility subscale was found. In our study rasagiline as add-on antiparkinsonian therapy significantly improved mobility, freezing of gait and quality of life. The positive effect on freezing of gait appears to be related to improvement of mobility.

The effects of the Kumamoto earthquake on the clinical symptoms of patients with Parkinson's disease.

PubMed

Hori, Hiroko; Kuratomi, Aki; Ishizaki, Masatoshi; Sakamoto, Tetsuro; Nishida, Yasuto; Ando, Yukio

2017-08-31

Our hospital is the designated treatment base for intractable neurological diseases in the Kumamoto Prefecture. It is located in the center of the prefecture where the major 7.3-magnitude Kumamoto earthquake was recorded in 2016. In order to examine whether this earthquake affected the clinical symptoms of patients with Parkinson's disease in this hospital, we investigated outpatients examined up to 4 weeks after the earthquake. The subjects were 26 consecutive patients without any changes in anti-Parkinson's disease treatment or their attending physician during the examination period. All of the items in Part III of the Unified Parkinson's Disease Rating Scale (UPDRS), which is a clinician-scored scale for monitoring and evaluating motor function, were confirmed with the subjects before and after the earthquakes. After the earthquakes, worsened symptoms were found in 7 patients and 7 patients felt better. On the UPDRS, worsened symptoms were most commonly found among the items examining "muscle rigidity" and "slowness of movement and decreased movement" among the 7 patients with exacerbated symptoms. After the earthquake, clinical symptoms worsened significantly in women (P = 0.0188), patients with mild symptoms (P = 0.0111), and those who suffered a high degree of personal loss, such as those whose homes were damaged, who were forced to take refuge, or who had to sleep in their car (P = 0.0184). The mental and emotional burden due to the earthquake might be particularly high in the group of patients with worsened symptoms, suggestive of a relationship between stress and the exacerbation of parkinsonian symptoms.

Validation of an ambulatory capacity measure in Parkinson disease: a construct derived from the Unified Parkinson's Disease Rating Scale.

PubMed

Parashos, Sotirios A; Elm, Jordan; Boyd, James T; Chou, Kelvin L; Dai, Lin; Mari, Zoltan; Morgan, John C; Sudarsky, Lewis; Wielinski, Catherine L

2015-01-01

A construct calculated as the sum of items 13-15, 29, 30 of the Unified Parkinson's Disease Rating Scale (UPDRS) has been used as an "Ambulatory Capacity Measure" (ACM) in Parkinson disease (PD). Its construct validity has never been examined. A similar construct, consisting of the mean value of the same UPDRS items has been used under the acronym PIGD as a measure of postural instability and gait disorder in PD. To examine the construct validity of the ACM and PIGD in PD. We analyzed data in an existing database of 340 PD patients, Hoehn and Yahr stages (HYS) 1-5 who participated in a study of falls. Number of falls (NOF) was recorded over 4 weeks, and UPDRS (mental, ADL, and motor subscales), HYS, Activities Based Confidence Scale (ABC), Freezing of Gait Questionnaire (FOG), Five Times Sit-to-Stand (FTSS), Timed Up-and Go (TUG), Gait Velocity (GV), and Berg Balance Scale (BBS) evaluations were performed. Internal consistency was assessed by Cronbach's alpha. Construct validity was assessed through correlations of the ACM and PIGD to these measures and to their summed-ranks. A coefficient of determination was calculated through linear regression. Mean age was 71.4, mean age at diagnosis 61.4 years; 46% were women; mean UPDRS subscale scores were: Mental 3.7; ADL 15.7; motor: 27.1; mean ACM was 6.51, and mean PIGD 1.30. Cronbach's alpha was 0.78 for both ACM and PIGD. Spearman correlation coefficients between the ACM/PIGD and ABC, FOG, TUG, GV and BBS were 0.69, 0.72, 0.67, 0.58, and 0.70 respectively. Correlation between the ACM/PIGD and summed-ranks of HYS, NOF, ABC, FOG, FTSS, TUG, GV and BBS was high (Spearman r = 0.823, p < 0.0001); 68% of the variability in the summed-ranks was explained by ACM/PIGD. The ACM and the PIGD are valid global measures and accurately reflect the combined effects of the various components of ambulatory capacity in PD patients with HY stages 1-4.

A combined pharmacokinetic/pharmacodynamic model of levodopa motor response and dyskinesia in Parkinson's disease patients.

PubMed

Simon, N; Viallet, F; Boulamery, A; Eusebio, A; Gayraud, D; Azulay, J-P

2016-04-01

Levodopa is the reference treatment for Parkinson's disease. However, after several years of treatment, dyskinesia may occur and strategies to overcome this side effect still need to be explored. We identified a unique population pharmacokinetic/pharmacodynamic model in Parkinson's disease to investigate the relationship and dissociability of motor response and dyskinesia. Thirty parkinsonian patients (Hoehn and Yahr stages 3-4), treated with levodopa and suffering from peak-dose dyskinesia, were included in a prospective open-label study. They received a single dose of levodopa equal to 150 % of their usual daily dose. Blood samples, motor evaluations (UPDRS III scale) and peak-dose dyskinesia (Goetz scale) were examined after administration. A population pharmacokinetic/pharmacodynamic (PK/PD) model was developed using NONMEM software. Pharmacokinetic analysis identified a one-compartment model with the following parameter values [bootstrap 95 % CI]: absorption rate constant (KA) 1.86 1/h [1.08-3.25], clearance 36.6 L/h [31.3-42.8], and volume of distribution 42.9 L [34.3-52.3]. Between-subject variability was 122 % [71-183] and 38 % [26-47] for KA and clearance, respectively. Residual variability was 1120 μg/L [886-1290]. UPDRS III and dyskinesia were best described with an effect compartment and similar KE0 values of 1.37 1/h [1.01-1.77]. For UPDRS III, the E0, EC50, Emax, and Hill coefficient were 31.4 [28.4-35.3], 1410 μg/L [1200-1700], 0.72 [0.71-0.75], and 4.26 [3.20-5.58], respectively. For dyskinesia, the EC50 and Emax were 6280 μg/L [3420-37,900] and 17.9 [12.3-80.8], respectively. Residual variability was 3.15 [2.75-3.53] for UPDRS III and 2.66 [1.94-3.51] for dyskinesia. No covariates influenced the parameters. In patients treated with levodopa and suffering from dyskinesia, the motor response and dyskinesia have close onsets and duration effects. Maximal motor response tends to be inevitably associated with dyskinesia.

Causes and risk factors of falls in patients with Parkinson's disease.

PubMed

Rudzińska, Monika; Bukowczan, Sylwia; Banaszkiewicz, Krzysztof; Stozek, Joanna; Zajdel, Katarzyna; Szczudlik, Andrzej

2008-01-01

Falls are a common and serious problem among Parkinson's disease (PD) patients. However, knowledge about the causes and risk factors of falls is limited. There have been a few attempts to classify the causes of falls. The classification suggested by Olanow seems to be the most comprehensive one. The aim of this study was to analyze retrospectively the causes of falls and risk factors of falls in PD patients. One hundred and four patients with moderately advanced PD were included in the study. The patients were asked to describe the circumstances and consequences of falls which occurred during 12 months preceding the examination. The falls were classified according to the Olanow classification of causes of falls. Fifty-two patients (50%) reported at least one fall during the previous year with a mean number of 1.5 falls per year. The most common causes of falls were environmental factors, sudden falls and postural instability. There were no falls caused by severe dyskinesia, drugs or cardiovascular disorders. The only independent risk factors of the recurrent falls identified in this study were UPDRS part II score (OR 1.17, 95% CI: 1.02-1.37) and Mini Mental State Examination score (OR 0.85, 95% CI: 0.72-0.99). Considering these results we may be able to prevent most falls by means of the education of patients about environmental factors and using adequate rehabilitation techniques concentrating on postural stability and gait.

Verbal and visual memory in patients with early Parkinson's disease: effect of levodopa.

PubMed

Singh, Sumit; Behari, Madhuri

2006-03-01

The effect of initiation of levodopa therapy on the memory functions in patients with Parkinson's disease remains poorly understood. To evaluate the effect of initiation of levodopa therapy on memory, in patients with early Parkinson's disease. Prospective case control study. Seventeen patients with early Parkinson's disease were evaluated for verbal memory using Rey's auditory verbal learning test, and visual memory using the Benton's visual retention test and Form sequence learning test. UPDRS scores, Hoehn and Yahr's Staging and Schwab and England scores of Activities of daily living. Hamilton's depression rating scale and MMSE were also evaluated. Six controls were also evaluated according to similar study protocol. Levodopa was then prescribed to the cases. Same tests were repeated on all the subjects after 12 weeks. The mean age of the patients was 59.8 (+ 12.9 yrs); mean disease duration of 3.26 (+ 2.06 yrs). The mean UPDRS scores of patients were 36.52 (+ 15.84). Controls were of a similar age and sex distribution. A statistically significant improvement in the scores on the UPDRS, Hamilton's depression scale, Schwab and England scale, and a statistically significant deterioration in the scores of visual memory was observed in patients with PD after starting levodopa, as compared to their baseline scores. There was no correlation between degree of deterioration and the dose of levodopa. Initiation of levodopa therapy in patients with early and stable Parkinson's disease is associated with deterioration in visual memory functions, with relative preservation of the verbal memory.

Effects of coordination and manipulation therapy for patients with Parkinson disease.

PubMed

Zhao, Mingming; Hu, Caiyou; Wu, Zhixin; Chen, Yu; Li, Zhengming; Zhang, Mingsheng

2017-09-01

To determine the effects of a new exercise training regimen, i.e. coordination and manipulation therapy (CMT), on motor, balance, and cardiac functions in patients with Parkinson disease (PD). We divided 36 PD patients into the CMT (n = 22) and control (n = 14) groups. The patients in the CMT group performed dry-land swimming (imitation of the breaststroke) and paraspinal muscle stretching for 30 min/workday for 1 year. The control subjects did not exercise regularly. The same medication regimen was maintained in both groups during the study. Clinical characteristics, Unified Parkinson's Disease Rating Scale (UPDRS) scores, Berg balance scale (BBS) scores, mechanical balance measurements, timed up and go (TUG) test, and left ventricular ejection fraction (LVEF) were compared at 0 (baseline), 6, and 12 months. Biochemical test results were compared at 0 and 12 months. The primary outcome was motor ability. The secondary outcome was cardiac function. In the CMT group, UPDRS scores significantly improved, TUG test time and step number significantly decreased, BBS scores significantly increased, and most mechanical balance measurements significantly improved after 1 year of regular exercise therapy (all p < 0.05). In the control group, UPDRS scores significantly deteriorated, TUG test time and step number significantly increased, BBS scores significantly decreased, and most mechanical balance measurements significantly worsened after 1 year (all P < 0.05). LVEF improved in the CMT group only (P = 0.01). This preliminary study suggests that CMT effectively improved mobility disorder, balance, and cardiac function in PD patients over a 1-year period.

Motor impairment predicts falls in specialized Alzheimer care units.

PubMed

Camicioli, Richard; Licis, Lisa

2004-01-01

We sought to identify clinical risk factors for falls in people with advanced Alzheimer disease (AD) in a prospective longitudinal observational study set in specialized AD care units. Forty-two patients with probable or possible AD were recruited. Age, sex, Mini-Mental Status Examination, Clinical Dementia Rating Scale, Neuropsychiatric Inventory/Nursing Home, Morse Fall Scale (MFS), modified Unified Parkinson's Rating Scale (mUPDRS), and gait parameters using a GAITRite Gold Walkway System with and without dual-task performance were examined. Time to a first fall was the primary outcome measure, and independent risk factors were identified. Participating subjects were old (non-fallers age, 82.3 +/- 6.7 years; fallers: 83.1 +/- 9.6 years; p = 0.76) and predominantly women (36 female/6 male). Fallers did not differ from non-fallers on any parameter except the MFS (non-fallers: 35.6 +/- 26.1; fallers: 54.4 +/- 29.8; p = 0.04), the UPDRS (non-fallers: 4.75 +/- 3.98; fallers: 7.61 +/- 4.3, p = 0.03) and cadence (steps per minute: non-fallers: 102.3 +/- 12.3; fallers: 91.7 +/- 16, p = 0.02). Fallers and non-fallers were equally affected by dual-task performance. The hazard ratios for MFS, UPDRS, and cadence were not affected by adjusting for age, sex, MMSE, or NPI scores. In conclusion, falls in advanced AD can be predicted using simple clinical measures of motor impairment or cadence. These measures may be useful for targeting interventions.

Bilateral adaptive deep brain stimulation is effective in Parkinson's disease.

PubMed

Little, Simon; Beudel, Martijn; Zrinzo, Ludvic; Foltynie, Thomas; Limousin, Patricia; Hariz, Marwan; Neal, Spencer; Cheeran, Binith; Cagnan, Hayriye; Gratwicke, James; Aziz, Tipu Z; Pogosyan, Alex; Brown, Peter

2016-07-01

Adaptive deep brain stimulation (aDBS) uses feedback from brain signals to guide stimulation. A recent acute trial of unilateral aDBS showed that aDBS can lead to substantial improvements in contralateral hemibody Unified Parkinson's Disease Rating Scale (UPDRS) motor scores and may be superior to conventional continuous DBS in Parkinson's disease (PD). We test whether potential benefits are retained with bilateral aDBS and in the face of concurrent medication. We applied bilateral aDBS in 4 patients with PD undergoing DBS of the subthalamic nucleus. aDBS was delivered bilaterally with independent triggering of stimulation according to the amplitude of β activity at the corresponding electrode. Mean stimulation voltage was 3.0±0.1 volts. Motor assessments consisted of double-blinded video-taped motor UPDRS scores that included both limb and axial features. UPDRS scores were 43% (p=0.04; Cohen's d=1.62) better with aDBS than without stimulation. Motor improvement with aDBS occurred despite an average time on stimulation (ToS) of only 45%. Levodopa was well tolerated during aDBS and led to further reductions in ToS. Bilateral aDBS can improve both axial and limb symptoms and can track the need for stimulation across drug states. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Abnormal pulmonary function and respiratory muscle strength findings in Chinese patients with Parkinson's disease and multiple system atrophy--comparison with normal elderly.

PubMed

Wang, Yao; Shao, Wei-bo; Gao, Li; Lu, Jie; Gu, Hao; Sun, Li-hua; Tan, Yan; Zhang, Ying-dong

2014-01-01

There have been limited comparative data regarding the investigations on pulmonary and respiratory muscle function in the patients with different parkinsonism disorders such as Parkinson's disease (PD) and multiple system atrophy (MSA) versus normal elderly. The present study is aiming to characterize the performance of pulmonary function and respiratory muscle strength in PD and MSA, and to investigate the association with severity of motor symptoms and disease duration. Pulmonary function and respiratory muscle strength tests were performed in 30 patients with PD, 27 with MSA as well as in 20 age-, sex-, height-, weight-matched normal elderly controls. All the patients underwent United Parkinson's disease rating scale (UPDRS) or united multiple system atrophy rating scale (UMSARS) separately as diagnosed. Vital capacity, forced expiratory volume in 1 second and forced vital capacity decreased, residual volume and ratio of residual volume to total lung capacity increased in both PD and MSA groups compared to controls (p<0.05). Diffusing capacity was decreased in the MSA group, compared with PD and normal elderly control groups (p<0.05). Respiratory muscle strength was lower in both PD and MSA groups than in controls (p<0.05). The values representing spirometry function and respiratory muscle strength were found to have a negative linear correlation with mean score of UPDRS-III in PD and mean score of UMSARS-I in MSA. Respiratory muscle strength showed a negative linear correlation with the mean score of UMSARS-II and disease duration in MSA patients. These findings suggest that respiratory dysfunction is involved in PD and MSA. Respiratory muscle strength is remarkably reduced, and some of the parameters correlate with disease duration and illness severity. The compromised respiratory function in neurodegenerative disorders should be the focus of further researches.

Item Response Theory as an Efficient Tool to Describe a Heterogeneous Clinical Rating Scale in De Novo Idiopathic Parkinson's Disease Patients.

PubMed

Buatois, Simon; Retout, Sylvie; Frey, Nicolas; Ueckert, Sebastian

2017-10-01

This manuscript aims to precisely describe the natural disease progression of Parkinson's disease (PD) patients and evaluate approaches to increase the drug effect detection power. An item response theory (IRT) longitudinal model was built to describe the natural disease progression of 423 de novo PD patients followed during 48 months while taking into account the heterogeneous nature of the MDS-UPDRS. Clinical trial simulations were then used to compare drug effect detection power from IRT and sum of item scores based analysis under different analysis endpoints and drug effects. The IRT longitudinal model accurately describes the evolution of patients with and without PD medications while estimating different progression rates for the subscales. When comparing analysis methods, the IRT-based one consistently provided the highest power. IRT is a powerful tool which enables to capture the heterogeneous nature of the MDS-UPDRS.

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

PubMed

Stocchi, Fabrizio; Borgohain, Rupam; Onofrj, Marco; Schapira, Anthony H V; Bhatt, Mohit; Lucini, Valentina; Giuliani, Rodolfo; Anand, Ravi

2012-01-01

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. Copyright © 2011 Movement Disorder Society.

Comparison of once-daily versus twice-daily combination of ropinirole prolonged release in Parkinson's disease.

PubMed

Yun, Ji Young; Kim, Han-Joon; Lee, Jee-Young; Kim, Young Eun; Kim, Ji Seon; Kim, Jong-Min; Jeon, Beom S

2013-09-02

Ropinirole prolonged release (RPR) is a once-daily formulation. However, there may be individual pharmacokinetic differences so that multiple dosing may be preferred in some individuals. This study compares once-daily and twice-daily RPR in patients with Parkinson's disease. This study was an open-label crossover study. We enrolled Parkinson's disease patients on dopamine agonist therapy with unsatisfactory control such as motor fluctuation, dyskinesia and sleep-related problems. Agonists were switched into equivalent dose of RPR. Subjects were consecutively enrolled into either once-daily first or twice-daily first groups, and received the same amount of RPR in a single and two divided dosing for 8 weeks respectively in a crossover manner without a washout period.The primary outcome was a questionnaire of the preference completed by patients in the last visit. The secondary outcome measures included the Unified Parkinson's Disease Rating Scale part 3 (mUPDRS), Hoehn and Yahr stage (H&Y); sleep questionnaire including overall quality of sleep, nocturnal off symptoms and early morning symptoms; Epworth Sleep Scale (ESS); compliances and patient global impression (PGI). A total of 82 patients were enrolled and 61 completed the study. 31 patients preferred twice-daily regimen, 17 preferred the once-daily regimen, and 13 had no preference. Their mean mUPDRS, H&Y, ESS, sleep quality, compliance and adverse events were not statistically different in both regimens. PGI-improvement on wearing off defined was better in twice-daily dosing regimen. RPR is a once-daily formulation, but multiple dosing was preferred in many patients. Multiple dosing of RPR might be a therapeutic option if once-daily dosing is unsatisfactory.

The Dynamic Gait Index in healthy older adults: the role of stair climbing, fear of falling and gender.

PubMed

Herman, Talia; Inbar-Borovsky, Noit; Brozgol, Marina; Giladi, Nir; Hausdorff, Jeffrey M

2009-02-01

The Dynamic Gait Index (DGI) was developed as a clinical tool to assess gait, balance and fall risk. Because the DGI evaluates not only usual steady-state walking, but also walking during more challenging tasks, it may be an especially sensitive test. The present investigation evaluated the DGI and its association with falls, fear of falling, depression, anxiety and other measures of balance and mobility in 278 healthy elderly individuals. Measures included the DGI, the Berg Balance Test (BBT), the Timed Up and Go (TUAG), the Mini-Mental State Exam (MMSE), the Unified Parkinson's Disease Rating Scale (UPDRS) motor part, the Activities-specific Balance Confidence (ABC) scale and the number of annual falls. The DGI was moderately correlated with the BBT (r=0.53; p<0.001), the TUAG (r=-0.42; p<0.001) and the ABC (r=0.49; p<0.001). Fallers performed worse on the DGI compared to non-fallers (p=0.029). Scores on the DGI were near perfect in men (23.3+/-1.2), but among women, there was a small, but significant (p<0.001) decrease (22.5+/-1.6). The reduction in the DGI score in women was due to stair climbing performance, with many women (65%) choosing to walk while holding a handrail, compared to only 39% of men. Scores on the BBT, the TUAG, the UPDRS and the MMSE were similar in men and women. Conversely, ABC scores and fall history were different. These findings suggest that the DGI, although susceptible to ceiling effects, appears to be an appropriate tool for assessing function in healthy older adults.

Loss of ability to work and ability to live independently in Parkinson's disease.

PubMed

Jasinska-Myga, Barbara; Heckman, Michael G; Wider, Christian; Putzke, John D; Wszolek, Zbigniew K; Uitti, Ryan J

2012-02-01

Ability to work and live independently is of particular concern for patients with Parkinson's disease (PD). We studied a series of PD patients able to work or live independently at baseline, and evaluated potential risk factors for two separate outcomes: loss of ability to work and loss of ability to live independently. The series comprised 495 PD patients followed prospectively. Ability to work and ability to live independently were based on clinical interview and examination. Cox regression models adjusted for age and disease duration were used to evaluate associations of baseline characteristics with loss of ability to work and loss of ability to live independently. Higher UPDRS dyskinesia score, UPDRS instability score, UPDRS total score, Hoehn and Yahr stage, and presence of intellectual impairment at baseline were all associated with increased risk of future loss of ability to work and loss of ability to live independently (P ≤ 0.0033). Five years after initial visit, for patients ≤70 years of age with a disease duration ≤4 years at initial visit, 88% were still able to work and 90% to live independently. These estimates worsened as age and disease duration at initial visit increased; for patients >70 years of age with a disease duration >4 years, estimates at 5 years were 43% able to work and 57% able to live independently. The information provided in this study can offer useful information for PD patients in preparing for future ability to perform activities of daily living. Copyright © 2011 Elsevier Ltd. All rights reserved.

Cannabis for dyskinesia in Parkinson disease: a randomized double-blind crossover study.

PubMed

Carroll, C B; Bain, P G; Teare, L; Liu, X; Joint, C; Wroath, C; Parkin, S G; Fox, P; Wright, D; Hobart, J; Zajicek, J P

2004-10-12

The long-term treatment of Parkinson disease (PD) may be complicated by the development of levodopa-induced dyskinesia. Clinical and animal model data support the view that modulation of cannabinoid function may exert an antidyskinetic effect. The authors conducted a randomized, double-blind, placebo-controlled crossover trial to examine the hypothesis that cannabis may have a beneficial effect on dyskinesia in PD. A 4-week dose escalation study was performed to assess the safety and tolerability of cannabis in six PD patients with levodopa-induced dyskinesia. Then a randomized placebo-controlled crossover study (RCT) was performed, in which 19 PD patients were randomized to receive oral cannabis extract followed by placebo or vice versa. Each treatment phase lasted for 4 weeks with an intervening 2-week washout phase. The primary outcome measure was a change in Unified Parkinson's Disease Rating Scale (UPDRS) (items 32 to 34) dyskinesia score. Secondary outcome measures included the Rush scale, Bain scale, tablet arm drawing task, and total UPDRS score following a levodopa challenge, as well as patient-completed measures of a dyskinesia activities of daily living (ADL) scale, the PDQ-39, on-off diaries, and a range of category rating scales. Seventeen patients completed the RCT. Cannabis was well tolerated, and had no pro- or antiparkinsonian action. There was no evidence for a treatment effect on levodopa-induced dyskinesia as assessed by the UPDRS, or any of the secondary outcome measures. Orally administered cannabis extract resulted in no objective or subjective improvement in dyskinesias or parkinsonism.

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

PubMed

Borgohain, Rupam; Szasz, J; Stanzione, P; Meshram, C; Bhatt, M; Chirilineau, D; Stocchi, F; Lucini, V; Giuliani, R; Forrest, E; Rice, P; Anand, R

2014-02-01

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 The Authors. Movement Disorders published by Wiley on behalf of the International Parkinson and Movement Disorder Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Automated gait and balance parameters diagnose and correlate with severity in Parkinson disease.

PubMed

Dewey, D Campbell; Miocinovic, Svjetlana; Bernstein, Ira; Khemani, Pravin; Dewey, Richard B; Querry, Ross; Chitnis, Shilpa; Dewey, Richard B

2014-10-15

To assess the suitability of instrumented gait and balance measures for diagnosis and estimation of disease severity in PD. Each subject performed iTUG (instrumented Timed-Up-and-Go) and iSway (instrumented Sway) using the APDM(®) Mobility Lab. MDS-UPDRS parts II and III, a postural instability and gait disorder (PIGD) score, the mobility subscale of the PDQ-39, and Hoehn & Yahr stage were measured in the PD cohort. Two sets of gait and balance variables were defined by high correlation with diagnosis or disease severity and were evaluated using multiple linear and logistic regressions, ROC analyses, and t-tests. 135 PD subjects and 66 age-matched controls were evaluated in this prospective cohort study. We found that both iTUG and iSway variables differentiated PD subjects from controls (area under the ROC curve was 0.82 and 0.75 respectively) and correlated with all PD severity measures (R(2) ranging from 0.18 to 0.61). Objective exam-based scores correlated more strongly with iTUG than iSway. The chosen set of iTUG variables was abnormal in very mild disease. Age and gender influenced gait and balance parameters and were therefore controlled in all analyses. Our study identified sets of iTUG and iSway variables which correlate with PD severity measures and differentiate PD subjects from controls. These gait and balance measures could potentially serve as markers of PD progression and are under evaluation for this purpose in the ongoing NIH Parkinson Disease Biomarker Program. Copyright © 2014 Elsevier B.V. All rights reserved.

Automated Gait and Balance Parameters Diagnose and Correlate with Severity in Parkinson Disease

PubMed Central

Dewey, Daniel C.; Miocinovic, Svjetlana; Bernstein, Ira; Khemani, Pravin; Dewey, Richard B.; Querry, Ross; Chitnis, Shilpa; Dewey, Richard B.

2014-01-01

Objective To assess the suitability of instrumented gait and balance measures for diagnosis and estimation of disease severity in PD. Methods Each subject performed iTUG (instrumented Timed-Up-and-Go) and iSway (instrumented Sway) using the APDM® Mobility Lab. MDS-UPDRS parts II and III, a postural instability and gait disorder (PIGD) score, the mobility subscale of the PDQ-39, and Hoehn & Yahr stage were measured in the PD cohort. Two sets of gait and balance variables were defined by high correlation with diagnosis or disease severity and were evaluated using multiple linear and logistic regressions, ROC analyses, and t-tests. Results 135 PD subjects and 66 age-matched controls were evaluated in this prospective cohort study. We found that both iTUG and iSway variables differentiated PD subjects from controls (area under the ROC curve was 0.82 and 0.75 respectively) and correlated with all PD severity measures (R2 ranging from 0.18 to 0.61). Objective exam-based scores correlated more strongly with iTUG than iSway. The chosen set of iTUG variables was abnormal in very mild disease. Age and gender influenced gait and balance parameters and were therefore controlled in all analyses. Interpretation Our study identified sets of iTUG and iSway variables which correlate with PD severity measures and differentiate PD subjects from controls. These gait and balance measures could potentially serve as markers of PD progression and are under evaluation for this purpose in the ongoing NIH Parkinson Disease Biomarker Program. PMID:25082782

Evaluation of the efficacy and safety of adjuvant treatment to levodopa therapy in Parkinson s disease patients with motor complications.

PubMed

Stowe, Rebecca; Ives, Natalie; Clarke, Carl E; Deane, Katherine; Wheatley, Keith; Gray, Richard; Handley, Kelly; Furmston, Alex

2010-07-07

One of the complications of long-term treatment of Parkinson's disease (PD) with levodopa is the development of motor complications. Generally, when motor complications develop, clinicians add in an additional drug (to the levodopa regimen) from one of three other classes of anti-Parkinsonian treatments (dopamine agonists, catechol-O-methyl transferase inhibitors (COMTIs) or monoamine oxidase type B inhibitors (MAOBIs)). However, despite trials having shown that these drugs are beneficial compared to placebo, it remains unclear as to the best way to treat patients experiencing motor complications and whether one class of drug is more effective than another. This meta-analysis aims to assess more reliably the benefits and risks of the three classes of drugs (dopamine agonists, COMTIs and MAOBIs) currently used as adjuvant treatment to levodopa in PD patients suffering from motor complications. The three drug classes were compared with the aim of determining whether one class of drug provides better symptomatic control than another. We searched CENTRAL (The Cochrane Library), MEDLINE, EMBASE, PubMed, LILACS and Web of Science, plus major journals in the field, abstract books, conference proceedings and reference lists of retrieved publications. Randomised trials comparing an orally administered dopamine agonist, COMTI or MAOBI versus placebo, both on a background of levodopa therapy, in PD patients experiencing motor complications. Two authors independently extracted data on off-time, levodopa dose, motor complications, side-effects, treatment concordance, clinician-rated disability, mortality, quality of life and health economic data. Forty-four eligible trials, involving 8436 participants were identified. Compared to placebo, adjuvant therapy significantly reduced off-time (-1.05 hours/day, 95% confidence interval (CI) -1.19 to -0.90; P<0.00001), the required levodopa dose (-55.65 mg/day, CI -62.67 to -48.62; P<0.00001) and improved UPDRS scores (UPDRS ADL score: -1.31 points, CI -1.62 to -0.99; P<0.00001; UPDRS motor score: -2.84 points, CI -3.36 to -2.32; P<0.00001; UPDRS total score: -3.26 points, CI -4.52 to -2.00; P<0.00001). However, dyskinesia (odds ratio (OR) 2.50, CI 2.21 to 2.84; P<0.00001) and side-effects including constipation (OR 3.19, CI 2.17 to 4.68; P<0.00001), dizziness (OR 1.57, CI 1.30 to 1.90; P<0.00001), dry mouth (OR 2.33, CI 1.22 to 4.47; P=0.01), hallucinations (OR 2.16, CI 1.70 to 2.74; P<0.00001), hypotension (OR 1.47, CI 1.18 to 1.83; P=0.0007), insomnia (OR 1.38, CI 1.09 to 1.74; P=0.007), nausea (OR 1.78, CI 1.53 to 2.07; P<0.00001), somnolence (OR 1.87, CI 1.40 to 2.51; P<0.0001) and vomiting (OR 2.56, CI 1.67 to 3.93; P<0.0001) were all increased with adjuvant therapy.Indirect comparisons of the three drug classes suggested that dopamine agonists were more efficacious in reducing off-time (dopamine agonist: -1.54 hours/day; COMTI: -0.83 hours/day; MAOBI: -0.93 hours/day; test for heterogeneity between drug classes P=0.0003) and levodopa dose (dopamine agonist: -116 mg/day; COMTI: -52 mg/day; MAOBI: -29 mg/day; test for heterogeneity between drug classes P<0.00001). UPDRS scores also improved more with dopamine agonists than with COMTI or MAOBI (UPDRS total scores - dopamine agonist: -10.01 points versus COMTI: -1.46 points versus MAOBI: -2.20 points; test for heterogeneity between drug classes P<0.00001), although more dyskinesia were seen with dopamine agonists (OR 2.70) and COMTI (OR 2.50) than with MAOBI (OR 0.94) (test for heterogeneity between drug classes P=0.009). Although the increase in the overall incidence of side-effects was generally more marked with dopamine agonists (OR 1.52) and COMTI (OR 2.0) than with MAOBI (OR 1.32), heterogeneity between drug classes was only of borderline significance (P=0.07). Compared to placebo, adjuvant therapy reduces off-time, levodopa dose, and improves UPDRS scores in PD patients who develop motor complications on levodopa therapy. However, this is at the expense of increased dyskinesia and numerous other side-effects. Indirect comparisons suggest that dopamine agonist therapy may be more effective than COMTI and MAOBI therapy, which have comparable efficacy. However, as indirect comparisons should be interpreted with caution, direct head-to-head randomised trials assessing the impact of these different drug classes on overall patient-rated quality of life are needed.

Predictive Big Data Analytics: A Study of Parkinson's Disease Using Large, Complex, Heterogeneous, Incongruent, Multi-Source and Incomplete Observations.

PubMed

Dinov, Ivo D; Heavner, Ben; Tang, Ming; Glusman, Gustavo; Chard, Kyle; Darcy, Mike; Madduri, Ravi; Pa, Judy; Spino, Cathie; Kesselman, Carl; Foster, Ian; Deutsch, Eric W; Price, Nathan D; Van Horn, John D; Ames, Joseph; Clark, Kristi; Hood, Leroy; Hampstead, Benjamin M; Dauer, William; Toga, Arthur W

2016-01-01

A unique archive of Big Data on Parkinson's Disease is collected, managed and disseminated by the Parkinson's Progression Markers Initiative (PPMI). The integration of such complex and heterogeneous Big Data from multiple sources offers unparalleled opportunities to study the early stages of prevalent neurodegenerative processes, track their progression and quickly identify the efficacies of alternative treatments. Many previous human and animal studies have examined the relationship of Parkinson's disease (PD) risk to trauma, genetics, environment, co-morbidities, or life style. The defining characteristics of Big Data-large size, incongruency, incompleteness, complexity, multiplicity of scales, and heterogeneity of information-generating sources-all pose challenges to the classical techniques for data management, processing, visualization and interpretation. We propose, implement, test and validate complementary model-based and model-free approaches for PD classification and prediction. To explore PD risk using Big Data methodology, we jointly processed complex PPMI imaging, genetics, clinical and demographic data. Collective representation of the multi-source data facilitates the aggregation and harmonization of complex data elements. This enables joint modeling of the complete data, leading to the development of Big Data analytics, predictive synthesis, and statistical validation. Using heterogeneous PPMI data, we developed a comprehensive protocol for end-to-end data characterization, manipulation, processing, cleaning, analysis and validation. Specifically, we (i) introduce methods for rebalancing imbalanced cohorts, (ii) utilize a wide spectrum of classification methods to generate consistent and powerful phenotypic predictions, and (iii) generate reproducible machine-learning based classification that enables the reporting of model parameters and diagnostic forecasting based on new data. We evaluated several complementary model-based predictive approaches, which failed to generate accurate and reliable diagnostic predictions. However, the results of several machine-learning based classification methods indicated significant power to predict Parkinson's disease in the PPMI subjects (consistent accuracy, sensitivity, and specificity exceeding 96%, confirmed using statistical n-fold cross-validation). Clinical (e.g., Unified Parkinson's Disease Rating Scale (UPDRS) scores), demographic (e.g., age), genetics (e.g., rs34637584, chr12), and derived neuroimaging biomarker (e.g., cerebellum shape index) data all contributed to the predictive analytics and diagnostic forecasting. Model-free Big Data machine learning-based classification methods (e.g., adaptive boosting, support vector machines) can outperform model-based techniques in terms of predictive precision and reliability (e.g., forecasting patient diagnosis). We observed that statistical rebalancing of cohort sizes yields better discrimination of group differences, specifically for predictive analytics based on heterogeneous and incomplete PPMI data. UPDRS scores play a critical role in predicting diagnosis, which is expected based on the clinical definition of Parkinson's disease. Even without longitudinal UPDRS data, however, the accuracy of model-free machine learning based classification is over 80%. The methods, software and protocols developed here are openly shared and can be employed to study other neurodegenerative disorders (e.g., Alzheimer's, Huntington's, amyotrophic lateral sclerosis), as well as for other predictive Big Data analytics applications.

Disease progress and response to treatment as predictors of survival, disability, cognitive impairment and depression in Parkinson's disease

PubMed Central

Vu, Thuy C.; Nutt, John G.; Holford, Nicholas H. G.

2012-01-01

AIM To describe the time to clinical events (death, disability, cognitive impairment and depression) in Parkinson's disease using the time course of disease status and treatment as explanatory variables. METHODS Disease status based on the Unified Parkinson's Disease Rating Scale (UPDRS) and the time to clinical outcome events were obtained from 800 patients who initially had early Parkinson's disease. Parametric hazard models were used to describe the time to the events of interest. RESULTS Time course of disease status (severity) was an important predictor of clinical outcome events. There was an increased hazard ratio for death 1.4 (95% CI 1.31, 149), disability 2.75 (95% CI 2.30, 3.28), cognitive impairment 4.35 (95% CI 1.94, 9.74), and depressive state 1.43 (95% CI 1.26, 1.63) with each 10 unit increase of UPDRS. Age at study entry increased the hazard with hazard ratios of 49.1 (95% CI 8.7, 278) for death, 4.76 (95% CI 1.10, 20.6) for disability and 90.0 (95% CI 63.3–128) for cognitive impairment at age 60 years. Selegiline treatment had independent effects as a predictor of death at 8 year follow-up with a hazard ratio of 2.54 (95% CI 1.51, 4.25) but had beneficial effects on disability with a hazard ratio of 0.363 (95% CI 0.132, 0.533) and depression with a hazard ratio of 0.372 (95% CI 0.12, 0.552). CONCLUSIONS Our findings show that the time course of disease status based on UPDRS is a much better predictor of future clinical events than any baseline disease characteristic. Continued selegiline treatment appears to increase the hazard of death. PMID:22300470

Prevalence of fatigue in Parkinson disease and its clinical correlates.

PubMed

Stocchi, Fabrizio; Abbruzzese, Giovanni; Ceravolo, Roberto; Cortelli, Pietro; D'Amelio, Marco; De Pandis, Maria F; Fabbrini, Giovanni; Pacchetti, Claudio; Pezzoli, Gianni; Tessitore, Alessandro; Canesi, Margherita; Iannacone, Claudio; Zappia, Mario

2014-07-15

To assess in a noninterventional setting the prevalence and severity of fatigue in patients with Parkinson disease (PD). This was a cross-sectional study conducted in Italian patients with PD. Objectives included the evaluation of the current prevalence and severity of fatigue in patients with PD measured using the 16-item Parkinson Fatigue Scale (PFS-16), distressing fatigue (defined as a PFS-16 mean score ≥3.3), and assessment of its clinical correlates. A total of 402 patients were enrolled and 394 patients completed the PFS-16 questionnaire with a PFS-16 mean (±SD) score of 2.87 ± 0.99. Of these, 136 patients (33.8%) reported distressing fatigue (PFS-16 mean score ≥3.3). Patients with distressing fatigue were older (p = 0.044) and had a longer duration of PD (p < 0.0001) than those without distressing fatigue. The presence of distressing fatigue was associated with higher total Unified Parkinson's Disease Rating Scale (UPDRS) scores, poorer quality of life (39-item Parkinson's Disease Questionnaire [PDQ-39]), worse social and psychological behaviors, a higher severity of depressive symptoms, and a higher prevalence of sleep disorders (all p < 0.001). Logistic regression analyses revealed that higher total UPDRS scores, female sex, depression, sleep disorders, as well as higher UPDRS activities of daily living scores and PDQ-39 mobility scores increase the likelihood of distressing fatigue in patients with PD. Approximately one-third of patients with PD have distressing fatigue, which is significantly associated with depression and sleep disorders. The fact that the presence of fatigue worsens patient quality of life supports the need to better diagnose and treat this debilitating symptom. © 2014 American Academy of Neurology.

Cognitive impairment in Parkinson's disease: Association between patient-reported and clinically measured outcomes.

PubMed

Mills, Kelly A; Mari, Zoltan; Pontone, Gregory M; Pantelyat, Alexander; Zhang, Angela; Yoritomo, Nadine; Powers, Emma; Brandt, Jason; Dawson, Ted M; Rosenthal, Liana S

2016-12-01

In Parkinson's disease, the association between objective and patient-reported measures of cognitive dysfunction is unknown and highly relevant to research and clinical care. To determine which cognitive domain-specific Montreal Cognitive Assessment (MoCA) subscores are most strongly associated with patient-reported cognitive impairment on question 1 (Q1) of the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). We analyzed data from 759 PD participants and 481 persons without PD with in a retrospective, cross sectional analysis using data from the NINDS Parkinson's Disease Biomarkers Program (PDBP), a longitudinal, multicenter biomarker study. The relationship between a patient-reported cognitive rating (MDS-UPDRS q1.1) and objective cognitive assessments (MoCA) was assessed using multinomial logistic regression modeling and the outcomes reported as conditional odds ratios (cOR's) representing the relative odds of a participant reporting cognitive impairment that is "slight" versus "normal" on MDS-UPDRSq1.1 for a one unit increase in a MoCA sub-score, adjusted for age and education. In PD participants, changes in visuospatial-executive performance and memory had the most significant impact on subjective cognitive impairment. A 1-point increase in visuospatial-executive function decreased the chance of reporting a MDS-UPDRS Q1 score of "slight" versus "normal" by a factor of 0.686 (p < 0.001) and each 1 point improvement in delayed recall decreased the odds of reporting "slight" cognitive impairment by a factor of 0.836 (p < 0.001). Conversion from a PD patient's report of "normal" to "slight" cognitive impairment may be associated with changes in visuospatial-executive dysfunction and memory more than other cognitive domains. Copyright © 2016 Elsevier Ltd. All rights reserved.

Deep Brain Stimulation for Parkinson Disease in the Philippines: Outcomes of the Philippine Movement Disorder Surgery Center.

PubMed

Diestro, Jose Danilo B; Vesagas, Theodor S; Teleg, Rosalia A; Aguilar, Jose A; Anlacan, Joseph P; Jamora, Roland Dominic G

2018-04-28

Deep brain stimulation (DBS) is an established treatment modality for Parkinson disease (PD). The first DBS for PD in the Philippines was performed at the Philippine Movement Disorder Surgery Center in 2006. There are no Philippine data on DBS for PD. We aim to determine the motor improvement and reduction in medication dosage of all patients with PD who underwent DBS at the Philippine Movement Disorder Surgery Center. This is a retrospective study of all patients with PD (n = 17) who underwent DBS from 2006 to 2016. The change in the Unified Parkinson's Disease Rating Scale (UPDRS) motor and levodopa equivalent dose were determined. There was a statistically significant reduction in the UPDRS motor in all patients off medication at 3 months (48.2%; P = 0.004), 1 year (47.3%; P = 0.026), 2 years (48.4%; P = 0.021), and 3 years (66.0%; P = 0.032) after DBS and on medication at 3 months (43.3%; P = 0.023), 6 months (24.7%; P = 0.053), and 1 year (38.1%; P = 0.033). A significant reduction in the dosage of PD medications was also seen until the second year of follow-up (52.3%; P < 0.001). Adverse events included an attempted suicide and a device-related infection. DBS for PD improves the UPDRS motor score in the off-medication and on-medication state, with the maximal benefit seen at 3 years after surgery and reduces PD medication dosage by half. Although the benefit from DBS is undeniable, the high cost of the procedure precludes more patients from benefitting from it. There is a need for government support to expand access to DBS. Copyright © 2018 Elsevier Inc. All rights reserved.

Prediction of individual clinical scores in patients with Parkinson's disease using resting-state functional magnetic resonance imaging.

PubMed

Hou, YanBing; Luo, ChunYan; Yang, Jing; Ou, RuWei; Song, Wei; Wei, QianQian; Cao, Bei; Zhao, Bi; Wu, Ying; Shang, Hui-Fang; Gong, QiYong

2016-07-15

Neuroimaging holds the promise that it may one day aid the clinical assessment. However, the vast majority of studies using resting-state functional magnetic resonance imaging (fMRI) have reported average differences between Parkinson's disease (PD) patients and healthy controls, which do not permit inferences at the level of individuals. This study was to develop a model for the prediction of PD illness severity ratings from individual fMRI brain scan. The resting-state fMRI scans were obtained from 84 patients with PD and the Unified Parkinson's Disease Rating Scale-III (UPDRS-III) scores were obtained before scanning. The RVR method was used to predict clinical scores (UPDRS-III) from fMRI scans. The application of RVR to whole-brain resting-state fMRI data allowed prediction of UPDRS-III scores with statistically significant accuracy (correlation=0.35, P-value=0.001; mean sum of squares=222.17, P-value=0.002). This prediction was informed strongly by negative weight areas including prefrontal lobe and medial occipital lobe, and positive weight areas including medial parietal lobe. It was suggested that fMRI scans contained sufficient information about neurobiological change in patients with PD to permit accurate prediction about illness severity, on an individual subject basis. Our results provided preliminary evidence, as proof-of-concept, to support that fMRI might be possible to be a clinically useful quantitative assessment aid in PD at individual level. This may enable clinicians to target those uncooperative patients and machines to replace human for a more efficient use of health care resources. Copyright © 2016 Elsevier B.V. All rights reserved.

Motor and non-motor symptoms of Parkinson's disease and their impact on quality of life and on different clinical subgroups.

PubMed

Berganzo, K; Tijero, B; González-Eizaguirre, A; Somme, J; Lezcano, E; Gabilondo, I; Fernandez, M; Zarranz, J J; Gómez-Esteban, J C

The aim of the present study is to analyse the influence that motor and non-motor symptoms have on the quality of life (QoL) of patients with Parkinson's disease (PD), and to study the relationship between the two types of symptoms. This cross-sectional study included 103 patients with PD (55 men and 48 women). Quality of life was measured on the PDQ-39 scale. The UPDRS scale (I-IV) was also used, and different items were grouped to analyse the presence of tremor, rigidity, bradykinesia, and axial symptoms. The non-motor symptoms scale (NMSS) was administered to assess non-motor symptoms. We performed correlation analyses between different scales to analyse the influence of motor and non-motor symptoms on QoL. Correlations were observed between the PDQ-39 summary index (PDQ39_SI) and the NMSS (correlation coefficient [cc], 0.56; p<.001), UPDRS III (cc, 0.44; p< .001) and UPDRS IV (cc, 0.37; p<.001) scores. The strongest correlation was between cognitive symptoms and mood. The analysis pointed to a direct relationship between the NMSS score and axial symptoms (cc, 0.384; p<.01), bradykinesia (cc, 0.299; p<.01), and to a lesser extent, rigidity (cc, 0.194; p<.05). No relationship was observed between presence of tremor and the NMSS score. Cognitive symptoms and mood exert the most influence on QoL of patients with PD. We found at least two phenotypes; one with predominantly axial symptoms, with significant involvement of non-motor symptoms, and a tremor-associated phenotype in which these symptoms are less prevalent. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Rasagiline in Parkinson's disease: a review based on meta-analysis of clinical data.

PubMed

Mínguez-Mínguez, Sara; Solís-García Del Pozo, Julián; Jordán, Joaquín

2013-08-01

Rasagiline (Azilect(®)) is a selective and irreversible monoamine oxidase B inhibitor, which is well tolerated, safe, improves motor symptoms, and prevents motor complications in Parkinson's disease (PD). Rasagiline is effective in monotherapy and as an adjunct to levodopa-therapy, with beneficial effects on quality-of-life parameters in early and late stages of PD. In this review, we compare the efficacy of rasagiline versus placebo for decreasing PD symptoms. Major databases (Medline, the Cochrane Library) were systematically searched to identify and select clinical randomized control trials of rasagiline. The Unified Parkinson Disease Rating Scale (UPDRS) for rasagiline monotherapy and reduction in off-time for combined treatment were the outcomes assessed. Rasagiline monotherapy, in early stages of the disease, reduces the UPDRS score [-3.06 (95% CI -3.81 to -2.31, p<0.00001) with rasagiline 1mg/day]. In combination with levodopa, 1mg/day of rasagiline reduced off-time [-0.93h (95% CI -1.17 to -0.69, p<0.00001)]. However, although rasagiline reduces the UPDRS score [-0.89 (95% CI from -1.78 to 0, p=0.05)] in trials with a delayed-start design, we found a disagreement between studies and doses, making it difficult to interpret this result. In conclusion, our results confirm the efficacy of rasagiline in PD, but the clinical significance of these data remains to be established. Furthermore, the delayed-start study design did not establish with certainty the neuroprotective effect of rasagiline. It is advisable to carry out comparative trials with other drugs used in Parkinson's disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

Small fiber neuropathy in Parkinson's disease: A clinical, pathological and corneal confocal microscopy study.

PubMed

Kass-Iliyya, Lewis; Javed, Saad; Gosal, David; Kobylecki, Christopher; Marshall, Andrew; Petropoulos, Ioannis N; Ponirakis, Georgios; Tavakoli, Mitra; Ferdousi, Maryam; Chaudhuri, Kallol Ray; Jeziorska, Maria; Malik, Rayaz A; Silverdale, Monty A

2015-12-01

Autonomic and somatic denervation is well established in Parkinson's disease (PD). (1) To determine whether corneal confocal microscopy (CCM) can non-invasively demonstrate small nerve fiber damage in PD. (2) To identify relationships between corneal nerve parameters, intraepidermal nerve fiber density (IENFD) and clinical features of PD. Twenty-six PD patients and 26 controls underwent CCM of both eyes. 24/26 PD patients and 10/26 controls underwent skin biopsies from the dorsa of both feet. PD patients underwent assessment of parasympathetic function [deep breathing heart rate variability (DB-HRV)], autonomic symptoms [scale for outcomes in Parkinson's disease - autonomic symptoms (SCOPA-AUT)], motor symptoms [UPDRS-III "ON"] and cumulative Levodopa dose. PD patients had significantly reduced corneal nerve fiber density (CNFD) with increased corneal nerve branch density (CNBD) and corneal nerve fiber length (CNFL) compared to controls. CNBD and CNFL but not CNFD correlated inversely with UPDRS-III and SCOPA-AUT. All CCM parameters correlated strongly with DB-HRV. There was no correlation between CCM parameters and disease duration, cumulative Levodopa dose or pain. IENFD was significantly reduced in PD compared to controls and correlated with CNFD and UPDRS-III. However, unlike CCM measures, IENFD correlated with disease duration and cumulative Levodopa dose but not with autonomic dysfunction. CCM identifies corneal nerve fiber pathology, which correlates with autonomic symptoms, parasympathetic deficits and motor scores in patients with PD. IENFD is also reduced and correlates with CNFD and motor symptoms but not parasympathetic deficits, indicating it detects different aspects of peripheral nerve pathology in PD. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

The Effect of Balance Training by Tetraks Interactive Balance System on Balance and Fall Risk in Parkinson's Patients: A Report of Four Cases.

PubMed

Balci, Nilay Çömük; Tonga, Eda; Gülşen, Mustafa

2013-09-01

This pilot study aimed to investigate the effect of balance training by Tetraks Interactive Balance System (TIBS) on balance and fall risk in patients with mild to moderate Parkinson's disease. Four patients with Parkinson's disease between the ages of 56 and 70 years (61.25±6.70) were applied balance training for 3 weeks by TIBS. Sociodemographic features and physical properties of the subjects were recorded. Their motor performance was evaluated by the Unified Parkinson's Disease Rating Scale (UPDRS), balance was measured using the Berg Balance Scale (BBS), Functional Reach Test (FRT), Timed Up and Go Test (TUG), and the Standing on One Leg Balance Test (SOL) and, their fall risks were evaluated by TIBS. Evaluations were performed twice, before and after treatment. Following training, Parkinson's patients showed improvements in UPDRS, TUG, BBS, FRT, SOL and fall risk. Balance training by TIBS has positive effects on balance and decreases fall risk in Parkinson's disease patients.

Is Irish set dancing feasible for people with Parkinson's disease in Ireland?

PubMed

Shanahan, Joanne; Morris, Meg E; Bhriain, Orfhlaith Ni; Volpe, Daniele; Richardson, Margaret; Clifford, Amanda M

2015-02-01

To investigate if community-based Irish set dancing is feasible in Irish adults with Parkinson's disease. Over an eight week period, ten participants attended one set dancing class per week and completed a home programme in parallel. Feasibility was assessed by monitoring adverse effects, participants' verbal feedback, compliance rates and feedback from an exit questionnaire. Participants were assessed using the Berg balance scale, 6-min walk test, UPDRS-3 and PDQ-39, before and after the intervention. No adverse effects were detected. Attendance at classes was 86%. Compliance with the home programme was 67%. Findings from the exit questionnaire showed participants enjoyed participating and reported improvements in aspects of health including balance. Quality of life improved with the dance programme and there was a trend toward improvement on the UPDRS-3. These findings suggest community-based Irish set dancing is a feasible form of exercise that can positively influence quality of life. Copyright © 2014 Elsevier Ltd. All rights reserved.

Subthalamic Synchronized Oscillatory Activity Correlates With Motor Impairment in Patients With Parkinson’s Disease

PubMed Central

Neumann, Wolf-Julian; Degen, Katharina; Schneider, Gerd-Helge; Brücke, Christof; Huebl, Julius; Brown, Peter; Kühn, Andrea A.

2016-01-01

Objective Beta band oscillations in the subthalamic nucleus (STN) have been proposed as a pathophysiological signature in patients with Parkinson’s disease (PD). The aim of this study was to investigate the potential association between oscillatory activity in the STN and symptom severity in PD. Methods Subthalamic local field potentials were recorded from 63 PD patients in a dopaminergic OFF state. Power-spectra were analyzed for the frequency range from 5 to 95 Hz and correlated with individual UPDRS-III motor scores in the OFF state. Results A correlation between total UPDRS-III scores and 8 to 35 Hz activity was revealed across all patients (ρ = 0.44, P <.0001). When correlating each frequency bin, a narrow range from 10 to 15 Hz remained significant for the correlation (false discovery rate corrected P <.05). Conclusion Our results show a correlation between local STN 8 to 35 Hz power and impairment in PD, further supporting the role of subthalamic oscillatory activity as a potential biomarker for PD. PMID:27548068

Changes in spontaneous brain activity in early Parkinson's disease.

PubMed

Yang, Hong; Zhou, Xiaohong Joe; Zhang, Min-Ming; Zheng, Xu-Ning; Zhao, Yi-Lei; Wang, Jue

2013-08-09

Resting state brain activity can provide valuable insights into the pathophysiology of Parkinson's disease (PD). The purpose of the present study was (a) to investigate abnormal spontaneous neuronal activity in early PD patients using resting-state functional MRI (fMRI) with a regional homogeneity (ReHo) method and (b) to demonstrate the potential of using changes in abnormal spontaneous neuronal activity for monitoring the progression of PD during its early stages. Seventeen early PD patients were assessed with the Unified Parkinson's Disease Rating Scale (UPDRS), the Hoehn and Yahr disability scale and the Mini-mental State Examination (MMSE) were compared with seventeen gender- and age-matched healthy controls. All subjects underwent MRI scans using a 1.5T General Electric Signa Excite II scanner. The MRI scan protocol included whole-brain volumetric imaging using a 3D inversion recovery prepared (IR-Prep) fast spoiled gradient-echo pulse sequence and 2D multi-slice (22 axial slices covering the whole brain) resting-state fMRI using an echo planar imaging (EPI) sequence. Images were analyzed in SPM5 together with a ReHo algorithm using the in-house software program REST. A corrected threshold of p<0.05 was determined by AlphaSim and used in statistical analysis. Compared with the healthy controls, the early PD group showed significantly increased ReHo in a number of brain regions, including the left cerebellum, left parietal lobe, right middle temporal lobe, right sub-thalamic nucleus areas, right superior frontal gyrus, middle frontal gyrus (MFG), right inferior parietal lobe (IPL), right precuneus lobe, left MFG and left IPL. Additionally, significantly reduced ReHo was also observed in the early PD patients in the following brain regions: the left putamen, left inferior frontal gyrus, right hippocampus, right anterior cingulum, and bilateral lingual gyrus. Moreover, in PD patients, ReHo in the left putamen was negatively correlated with the UPDRS scores (r=-0.69). These results indicate that the abnormal resting state spontaneous brain activity associated with patients with early PD can be revealed by Reho analysis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Impact of a Weekly Dance Class on the Functional Mobility and on the Quality of Life of Individuals with Parkinson’s Disease

PubMed Central

Heiberger, Lisa; Maurer, Christoph; Amtage, Florian; Mendez-Balbuena, Ignacio; Schulte-Mönting, Jürgen; Hepp-Reymond, Marie-Claude; Kristeva, Rumyana

2011-01-01

Individuals with Parkinson’s disease (PD) mainly suffer from motor impairments which increase the risk of falls and lead to a decline of quality of life. Several studies investigated the long-term effect of dance for people with PD. The aims of the present study were to investigate (i) the short-term effects of dance (i.e., the effect immediately after the dance class) on motor control in individuals with PD and (ii) the long-term effects of 8 months of participation in the weekly dance class on the quality of life of the PD patients and their caregivers. The dance lessons took place in a ballet studio and were led by a professional dancer. Eleven people with moderate to severe PD (58–85 years old) were subjected to a motor and quality of life assessments. With respect to the motor assessments the unified Parkinson disease rating scale III (UPDRS III), the timed up and go test (TUG), and the Semitandem test (SeTa) before and after the dance class were used. With respect to the quality of life and well-being we applied quality of life scale (QOLS) as well as the Westheimer questionnaire. Additionally, we asked the caregivers to fill out the Questionnaire for caregivers. We found a significant beneficial short-term effect for the total score of the UPDRS motor score. The strongest improvements were in rigidity scores followed by significant improvements in hand movements, finger taps, and facial expression. No significant changes were found for TUG and for SeTa. The results of the questionnaires showed positive effects of the dance class on social life, health, body-feeling and mobility, and on everyday life competences of the PD patients. Beneficial effect was also found for the caregivers. The findings demonstrate that dance has beneficial effect on the functional mobility of individuals with PD. Further, dance improves the quality of life of the patients and their caregivers. Dance may lead to better therapeutic strategies as it is engaging and enjoyable. PMID:22013420

Preserved serotonin transporter binding in de novo Parkinson's disease: negative correlation with the dopamine transporter.

PubMed

Strecker, Karl; Wegner, Florian; Hesse, Swen; Becker, Georg-Alexander; Patt, Marianne; Meyer, Philipp M; Lobsien, Donald; Schwarz, Johannes; Sabri, Osama

2011-01-01

Recent imaging and neuropathological studies indicate reduced serotonin transporter (SERT) in advanced Parkinson's disease (PD). However, data on SERT in early PD patients are sparse. Following the hypothesis that the serotonergic system is damaged early in PD, the aim of our study was to investigate SERT availability by means of PET imaging. Since the loss of dopaminergic neurons is the pathologic hallmark of PD and SERT might be associated with psychiatric co-morbidity, we further sought to correlate SERT availability with the availability of dopamine transporter (DAT) and depressive or motor symptoms in early PD. We prospectively recruited nine early PD patients (4 female, 5 male; 42-76 years) and nine age matched healthy volunteers (5 female, 4 male; 42-72 years). Diagnosis of PD was confirmed by the UK brain bank criteria and DAT imaging. SERT availability was measured by means of [11C]DASB PET. For neuropsychiatric assessment done on the day of PET we applied UPDRS parts I, II and III, Beck's Depression Inventory, Hamilton Rating Scale for Depression, Mini-Mental State Examination and Demtect. SERT was not reduced in any of 14 investigated regions of interest in the nine PD patients compared to healthy controls (p>0.13). SERT was negatively associated with DAT in the striatum (r=-0.69; p=0.04) but not within the midbrain. There was no correlation of SERT availability with depressive symptoms. No alteration of SERT binding in our patients suggests that the serotonergic system is remarkably preserved in early PD. Correlation with DAT might point to a compensatory regulation of the serotonergic system in early stages of PD.

Prevalence and clinical correlation of dysphagia in Parkinson disease: a study on Chinese patients.

PubMed

Ding, X; Gao, J; Xie, C; Xiong, B; Wu, S; Cen, Z; Lou, Y; Lou, D; Xie, F; Luo, W

2018-01-01

Dysphagia is relatively common in patients with Parkinson disease (PD) and can have a negative impact on their quality of life; therefore, it is imperative that its prevalence in PD patients is studied. The aim of this study was to explore the prevalence and clinical correlation of dysphagia in Chinese PD patients. We recruited 116 Chinese PD patients. A videofluoroscopic study of swallowing (VFSS) was used to identify dysphagia. Assessments, including water drinking test, relative motor symptoms, non-motor symptoms (NMS) and quality of life, were performed to analyze the risks of dysphagia. The prevalence of dysphagia was 87.1%. The comparison of demographic and clinical features between patients with and without dysphagia included sex, education level, disease course, Mini-mental State Examination (MMSE), Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), Question 6, 7 of the Unified Parkinson Disease Rating Scale (UPDRS Part II), Hoehn-Yahr stage (H&Y), water drinking test, 39-item Parkinson Disease Questionnaire (PDQ-39) and Non-Motor Symptoms Quest (NMSQ). We found significant correlations between dysphagia and age. Using age, disease course, and H&Y stage as the independent variable in our regression analysis for assessing the risk factors of dysphagia in PD patients, age and H&Y stage displayed a strong correlation as the risk factors. The risk of dysphagia in elderly PD patients is 1.078 times greater than that of younger PD patients. Also, the risk of dysphagia in PD patients of a greater H&Y staging is 3.260 times greater than that of lower staging PD patients. Our results suggest that dysphagia is common in Chinese PD patients. Older patients or those in higher H&Y stages are more likely to experience dysphagia. There is no correlation between dysphagia and PD duration.

Axial hypertonicity in Parkinson’s disease: Direct measurements of trunk and hip torque

PubMed Central

Wright, W.G.; Gurfinkel, V.S.; Nutt, J.; Horak, F.B.; Cordo, P.J.

2007-01-01

A cardinal feature of Parkinson’s disease (PD) is muscle hypertonicity, i.e. rigidity. Little is known about the axial tone in PD or the relation of hypertonia to functional impairment. We quantified axial rigidity to assess its relation to motor symptoms as measured by UPDRS and determine whether rigidity is affected by levodopa treatment. Axial rigidity was measured in 12 PD and 14 age-matched controls by directly measuring torsional resistance of the longitudinal axis to twisting (±10°). Feet were rotated relative to fixed hips (Hip Tone) or feet and hips were rotated relative to fixed shoulders (Trunk Tone). To assess tonic activity only, low constant velocity rotation (1°/s) and low acceleration (<12°/s2) were used to avoid eliciting phasic sensorimotor responses. Subjects stood during testing without changing body orientation relative to gravity. Body parts fixed against rotation could translate laterally within the boundaries of normal postural sway, but could not rotate. PD OFF-medication had higher axial rigidity (p<0.05) in hips (5.07 Nm) and trunk (5.30 Nm) than controls (3.51 Nm and 4.46 Nm, respectively), which didn’t change with levodopa (p>0.10). Hip-to-trunk torque ratio was greater in PD than controls (p<0.05) and unchanged by levodopa (p=0.28). UPDRS scores were significantly correlated with hip rigidity for PD OFF-medication (r=0.73, p<0.05). Torsional resistance to clockwise versus counter-clockwise axial rotation was more asymmetrical in PD than controls (p<0.05), however, there was no correspondence between direction of axial asymmetry and side of disease onset. In conclusion, these findings concerning hypertonicity may underlie functional impairments of posture and locomotion in PD. The absence of a levodopa effect on axial tone suggests axial and appendicular tone are controlled by separate neural circuits. PMID:17692315

Clinical Phenotype Predicts Early Staged Bilateral Deep Brain Stimulation in Parkinson’s Disease

PubMed Central

Sung, Victor W.; Watts, Ray L.; Schrandt, Christian J.; Guthrie, Stephanie; Wang, Deli; Amara, Amy W.; Guthrie, Barton L.; Walker, Harrison C.

2014-01-01

Object While many centers place bilateral DBS systems simultaneously, unilateral STN DBS followed by a staged contralateral procedure has emerged as a treatment option for many patients. However little is known about whether the preoperative phenotype predicts when staged placement of a DBS electrode in the opposite subthalamic nucleus will be required. We aimed to determine whether preoperative clinical phenotype predicts early staged placement of a second subthalamic deep brain stimulation (DBS) electrode in patients who undergo unilateral subthalamic DBS for Parkinson's disease (PD). Methods Eighty-two consecutive patients with advanced PD underwent unilateral subthalamic DBS contralateral to the most affected hemibody and had at least 2 years of follow-up. Multivariate logistic regression determined preoperative characteristics that predicted staged placement of a second electrode in the opposite subthalamic nucleus. Preoperative measurements included aspects of the Unified Parkinson Disease Rating Scale (UPDRS), motor asymmetry index, and body weight. Results At 2 years follow-up, 28 of the 82 patients (34%) had undergone staged placement of a contralateral electrode while the remainder chose to continue with unilateral stimulation. Statistically significant improvements in UPDRS total and part 3 scores were retained at the end of the 2 year follow-up period in both subsets of patients. Multivariate logistic regression showed that the most important predictors for early staged placement of a second subthalamic stimulator were low asymmetry index (odds ratio 13.4; 95% confidence interval 2.8, 64.9), high tremor subscore (OR 7.2; CI 1.5, 35.0), and low body weight (OR 5.5; CI 1.4, 22.3). Conclusions This single center study provides evidence that elements of the preoperative PD phenotype predict whether patients will require early staged bilateral subthalamic DBS. These data may aid in the management of patients with advanced PD who undergo subthalamic DBS. PMID:24074493

The Effect of Balance Training by Tetraks Interactive Balance System on Balance and Fall Risk in Parkinson’s Patients: A Report of Four Cases

PubMed Central

BALCI, Nilay Çömük; TONGA, Eda; GÜLŞEN, Mustafa

2013-01-01

This pilot study aimed to investigate the effect of balance training by Tetraks Interactive Balance System (TIBS) on balance and fall risk in patients with mild to moderate Parkinson’s disease. Four patients with Parkinson’s disease between the ages of 56 and 70 years (61.25±6.70) were applied balance training for 3 weeks by TIBS. Sociodemographic features and physical properties of the subjects were recorded. Their motor performance was evaluated by the Unified Parkinson’s Disease Rating Scale (UPDRS), balance was measured using the Berg Balance Scale (BBS), Functional Reach Test (FRT), Timed Up and Go Test (TUG), and the Standing on One Leg Balance Test (SOL) and, their fall risks were evaluated by TIBS. Evaluations were performed twice, before and after treatment. Following training, Parkinson’s patients showed improvements in UPDRS, TUG, BBS, FRT, SOL and fall risk. Balance training by TIBS has positive effects on balance and decreases fall risk in Parkinson’s disease patients. PMID:28360557

Pulse duration settings in subthalamic stimulation for Parkinson's disease

PubMed Central

Steigerwald, Frank; Timmermann, Lars; Kühn, Andrea; Schnitzler, Alfons; Reich, Martin M.; Kirsch, Anna Dalal; Barbe, Michael Thomas; Visser‐Vandewalle, Veerle; Hübl, Julius; van Riesen, Christoph; Groiss, Stefan Jun; Moldovan, Alexia‐Sabine; Lin, Sherry; Carcieri, Stephen; Manola, Ljubomir

2017-01-01

ABSTRACT Background Stimulation parameters in deep brain stimulation (DBS) of the subthalamic nucleus for Parkinson's disease (PD) are rarely tested in double‐blind conditions. Evidence‐based recommendations on optimal stimulator settings are needed. Results from the CUSTOM‐DBS study are reported, comparing 2 pulse durations. Methods A total of 15 patients were programmed using a pulse width of 30 µs (test) or 60 µs (control). Efficacy and side‐effect thresholds and unified PD rating scale (UPDRS) III were measured in meds‐off (primary outcome). The therapeutic window was the difference between patients’ efficacy and side effect thresholds. Results The therapeutic window was significantly larger at 30 µs than 60 µs (P = ·0009) and the efficacy (UPDRS III score) was noninferior (P = .00008). Interpretation Subthalamic neurostimulation at 30 µs versus 60 µs pulse width is equally effective on PD motor signs, is more energy efficient, and has less likelihood of stimulation‐related side effects. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. PMID:29165837

Imaging genetics approach to predict progression of Parkinson's diseases.

PubMed

Mansu Kim; Seong-Jin Son; Hyunjin Park

2017-07-01

Imaging genetics is a tool to extract genetic variants associated with both clinical phenotypes and imaging information. The approach can extract additional genetic variants compared to conventional approaches to better investigate various diseased conditions. Here, we applied imaging genetics to study Parkinson's disease (PD). We aimed to extract significant features derived from imaging genetics and neuroimaging. We built a regression model based on extracted significant features combining genetics and neuroimaging to better predict clinical scores of PD progression (i.e. MDS-UPDRS). Our model yielded high correlation (r = 0.697, p <; 0.001) and low root mean squared error (8.36) between predicted and actual MDS-UPDRS scores. Neuroimaging (from 123 I-Ioflupane SPECT) predictors of regression model were computed from independent component analysis approach. Genetic features were computed using image genetics approach based on identified neuroimaging features as intermediate phenotypes. Joint modeling of neuroimaging and genetics could provide complementary information and thus have the potential to provide further insight into the pathophysiology of PD. Our model included newly found neuroimaging features and genetic variants which need further investigation.

The effect of unilateral electrostimulation of the subthalamic nucleus on respiratory/phonatory subsystems of speech production in Parkinson's disease--a preliminary report.

PubMed

Wang, Emily; Verhagen Metman, Leo; Bakay, Roy; Arzbaecher, Jean; Bernard, Bryan

2003-01-01

This paper reports findings on the respiratory/phonatory subsystems from an on-going study investigating the effect of unilateral electrostimulation of the subthalamic nucleus (STN) on different speech subsystems in people with Parkinson's disease (PD). Speech recordings were made in the medication-off state at baseline, three months post surgery with stimulation-on, and with stimulation-off, in six right-handed PD patients. Subjects completed several speech tasks. Acoustic analyses of the maximally sustained vowel phonation were reported. The results were compared to the scores of the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS-III) obtained under the same conditions. Results showed that stimulation-on improved UPDRS-III scores in all six subjects. While mild improvement was observed for all subjects in the Stimulation-on condition, three subjects received left-STN stimulation showed a significant decline in vocal intensity and vowel duration from their baseline indicating the speech function was very susceptible to micro lesions due to the surgical procedure itself when the surgical site was in the dominant hemisphere.

A randomized controlled trial of movement strategies compared with exercise for people with Parkinson's disease.

PubMed

Morris, Meg E; Iansek, Robert; Kirkwood, Beth

2009-01-15

This randomized controlled clinical trial was conducted to compare the effects of movement rehabilitation strategies and exercise therapy in hospitalized patients with idiopathic Parkinson's disease. Participants were randomly assigned to a group that received movement strategy training or musculoskeletal exercises during 2 consecutive weeks of hospitalization. The primary outcome was disability as measured by the Unified Parkinson's Disease Rating Scale, UPDRS (motor and ADL components). Secondary outcomes were balance, walking speed, endurance, and quality of life. Assessments were carried out by blinded testers at baseline, after the 2 weeks of treatment and 3 months after discharge. The movement strategy group showed improvements on several outcome measures from admission to discharge, including the UPDRS, 10 m walk, 2 minute walk, balance, and PDQ39. However, from discharge to follow up there was significant regression in performance on the 2 minute walk and PDQ39. For the exercise group, quality of life improved significantly during inpatient hospitalization and this was retained at follow-up. Inpatient rehabilitation produces short term reductions in disability and improvements in quality of life in people with Parkinson's disease.

Comparative efficacy of selegiline versus rasagiline in the treatment of early Parkinson's disease.

PubMed

Marconi, S; Zwingers, T

2014-07-01

The monoamine oxidase B inhibitors selegiline and rasagiline have not been compared in head-to-head clinical trials in patients with early Parkinson's disease.  The aim of this review was to compare the efficacy of these two agents in this setting. Randomized, placebo-controlled trials with an endpoint of the mean change from baseline in the Unified Parkinson's Disease Rating Scale (UPDRS) total score were included. Analysis included calculation of the standardized mean differences (SMDs) with 95% confidence intervals (CIs) and Forest Plot analyses for comparisons of pooled results. Five studies with selegiline (n = 1029) and four with rasagiline (n = 820) were included. Treatment duration was 2.5-9 months. Both selegiline and rasagiline showed significant SMDs versus placebo (-0.690, 95% CI -0.811, -0.569 and -1.025, 95% CI -1.230, -0.820; respectively), indicating a significant effect of both drugs on UPDRS. The SMD between selegiline and rasagiline was not significantly different (SMD 0.079; 95% CI -0.010, +0.167). It appears that selegiline and rasagiline have comparable efficacy in improving Parkinsonian symptoms in patients with early stage disease.

Effects of a Flexibility and Relaxation Programme, Walking, and Nordic Walking on Parkinson's Disease

PubMed Central

Reuter, I.; Mehnert, S.; Leone, P.; Kaps, M.; Oechsner, M.; Engelhardt, M.

2011-01-01

Symptoms of Parkinson's disease (PD) progress despite optimized medical treatment. The present study investigated the effects of a flexibility and relaxation programme, walking, and Nordic walking (NW) on walking speed, stride length, stride length variability, Parkinson-specific disability (UPDRS), and health-related quality of life (PDQ 39). 90 PD patients were randomly allocated to the 3 treatment groups. Patients participated in a 6-month study with 3 exercise sessions per week, each lasting 70 min. Assessment after completion of the training showed that pain was reduced in all groups, and balance and health-related quality of life were improved. Furthermore, walking, and Nordic walking improved stride length, gait variability, maximal walking speed, exercise capacity at submaximal level, and PD disease-specific disability on the UPDRS in addition. Nordic walking was superior to the flexibility and relaxation programme and walking in improving postural stability, stride length, gait pattern and gait variability. No significant injuries occurred during the training. All patients of the Nordic walking group continued Nordic walking after completing the study. PMID:21603199

Predictive Big Data Analytics: A Study of Parkinson’s Disease Using Large, Complex, Heterogeneous, Incongruent, Multi-Source and Incomplete Observations

PubMed Central

Dinov, Ivo D.; Heavner, Ben; Tang, Ming; Glusman, Gustavo; Chard, Kyle; Darcy, Mike; Madduri, Ravi; Pa, Judy; Spino, Cathie; Kesselman, Carl; Foster, Ian; Deutsch, Eric W.; Price, Nathan D.; Van Horn, John D.; Ames, Joseph; Clark, Kristi; Hood, Leroy; Hampstead, Benjamin M.; Dauer, William; Toga, Arthur W.

2016-01-01

Background A unique archive of Big Data on Parkinson’s Disease is collected, managed and disseminated by the Parkinson’s Progression Markers Initiative (PPMI). The integration of such complex and heterogeneous Big Data from multiple sources offers unparalleled opportunities to study the early stages of prevalent neurodegenerative processes, track their progression and quickly identify the efficacies of alternative treatments. Many previous human and animal studies have examined the relationship of Parkinson’s disease (PD) risk to trauma, genetics, environment, co-morbidities, or life style. The defining characteristics of Big Data–large size, incongruency, incompleteness, complexity, multiplicity of scales, and heterogeneity of information-generating sources–all pose challenges to the classical techniques for data management, processing, visualization and interpretation. We propose, implement, test and validate complementary model-based and model-free approaches for PD classification and prediction. To explore PD risk using Big Data methodology, we jointly processed complex PPMI imaging, genetics, clinical and demographic data. Methods and Findings Collective representation of the multi-source data facilitates the aggregation and harmonization of complex data elements. This enables joint modeling of the complete data, leading to the development of Big Data analytics, predictive synthesis, and statistical validation. Using heterogeneous PPMI data, we developed a comprehensive protocol for end-to-end data characterization, manipulation, processing, cleaning, analysis and validation. Specifically, we (i) introduce methods for rebalancing imbalanced cohorts, (ii) utilize a wide spectrum of classification methods to generate consistent and powerful phenotypic predictions, and (iii) generate reproducible machine-learning based classification that enables the reporting of model parameters and diagnostic forecasting based on new data. We evaluated several complementary model-based predictive approaches, which failed to generate accurate and reliable diagnostic predictions. However, the results of several machine-learning based classification methods indicated significant power to predict Parkinson’s disease in the PPMI subjects (consistent accuracy, sensitivity, and specificity exceeding 96%, confirmed using statistical n-fold cross-validation). Clinical (e.g., Unified Parkinson's Disease Rating Scale (UPDRS) scores), demographic (e.g., age), genetics (e.g., rs34637584, chr12), and derived neuroimaging biomarker (e.g., cerebellum shape index) data all contributed to the predictive analytics and diagnostic forecasting. Conclusions Model-free Big Data machine learning-based classification methods (e.g., adaptive boosting, support vector machines) can outperform model-based techniques in terms of predictive precision and reliability (e.g., forecasting patient diagnosis). We observed that statistical rebalancing of cohort sizes yields better discrimination of group differences, specifically for predictive analytics based on heterogeneous and incomplete PPMI data. UPDRS scores play a critical role in predicting diagnosis, which is expected based on the clinical definition of Parkinson’s disease. Even without longitudinal UPDRS data, however, the accuracy of model-free machine learning based classification is over 80%. The methods, software and protocols developed here are openly shared and can be employed to study other neurodegenerative disorders (e.g., Alzheimer’s, Huntington’s, amyotrophic lateral sclerosis), as well as for other predictive Big Data analytics applications. PMID:27494614

Non-exercise physical activity attenuates motor symptoms in Parkinson disease independent from nigrostriatal degeneration.

PubMed

Snider, Jonathan; Müller, Martijn L T M; Kotagal, Vikas; Koeppe, Robert A; Scott, Peter J H; Frey, Kirk A; Albin, Roger L; Bohnen, Nicolaas I

2015-10-01

To investigate the relationship between time spent in non-exercise and exercise physical activity and severity of motor functions in Parkinson disease (PD). Increasing motor impairments of PD incline many patients to a sedentary lifestyle. We investigated the relationship between duration of both non-exercise and exercise physical activity over a 4-week period using the Community Health Activities Model Program for Seniors (CHAMPS) questionnaire and severity of clinical motor symptoms in PD. We accounted for the magnitude of nigrostriatal degeneration. Cross-sectional study. PD subjects, n = 48 (40 M); 69.4 ± 7.4 (56-84) years old; 8.4 ± 4.2 (2.5-20) years motor disease duration, mean UPDRS motor score 27.5 ± 10.3 (7-53) and mean MMSE score 28.4 ± 1.9 (22-30) underwent [(11)C]dihydrotetrabenazine (DTBZ) PET imaging to assess nigrostriatal denervation and completed the CHAMPS questionnaire and clinical assessment. Bivariate correlations showed an inverse relationship between motor UPDRS severity scores and duration of non-exercise physical activity (R = -0.37, P = 0.0099) but not with duration of exercise physical activity (R = -0.05, P = 0.76) over 4 weeks. Multiple regression analysis using UPDRS motor score as outcome variable demonstrated a significant regressor effect for duration of non-exercise physical activity (F = 6.15, P = 0.017) while accounting for effects of nigrostriatal degeneration (F = 4.93, P = 0.032), levodopa-equivalent dose (LED; F = 1.07, P = 0.31), age (F = 4.37, P = 0.043) and duration of disease (F = 1.46, P = 0.23; total model (F = 5.76, P = 0.0004). Non-exercise physical activity is a correlate of motor symptom severity in PD independent of the magnitude of nigrostriatal degeneration. Non-exercise physical activity may have positive effects on functional performance in PD. Published by Elsevier Ltd.

Color discrimination errors associate with axial motor impairments in Parkinson's disease.

PubMed

Bohnen, Nicolaas I; Haugen, Jacob; Ridder, Andrew; Kotagal, Vikas; Albin, Roger L; Frey, Kirk A; Müller, Martijn L T M

2017-01-01

Visual function deficits are more common in imbalance-predominant compared to tremor-predominant PD suggesting a pathophysiological role of impaired visual functions in axial motor impairments. To investigate the relationship between changes in color discrimination and motor impairments in PD while accounting for cognitive or other confounder factors. PD subjects (n=49, age 66.7±8.3 years; Hoehn & Yahr stage 2.6±0.6) completed color discrimination assessment using the Farnsworth-Munsell 100 Hue Color Vision Test, neuropsychological, motor assessments and [ 11 C]dihydrotetrabenazine vesicular monoamine transporter type 2 PET imaging. MDS-UPDRS sub-scores for cardinal motor features were computed. Timed up and go mobility and walking tests were assessed in 48 subjects. Bivariate correlation coefficients between color discrimination and motor variables were significant only for the Timed up and go (R S =0.44, P=0.0018) and the MDS-UPDRS axial motor scores (R S =0.38, P=0.0068). Multiple regression confounder analysis using the Timed up and go as outcome parameter showed a significant total model (F (5,43) = 7.3, P<0.0001) with significant regressor effects for color discrimination (standardized β=0.32, t=2.6, P=0.012), global cognitive Z-score (β=-0.33, t=-2.5, P=0.018), duration of disease (β=0.26, t=1.8, P=0.038), but not for age or striatal dopaminergic binding. The color discrimination test was also a significant independent regressor in the MDS-UPDRS axial motor model (standardized β=0.29, t=2.4, P=0.022; total model t (5,43) = 6.4, P=0.0002). Color discrimination errors associate with axial motor features in PD independent of cognitive deficits, nigrostriatal dopaminergic denervation, and other confounder variables. These findings may reflect shared pathophysiology between color discrimination visual impairments and axial motor burden in PD.

CSF Nrf2 and HSPA8 in Parkinson's disease patients with and without LRRK2 gene mutations.

PubMed

Loeffler, David A; Smith, Lynnae M; Coffey, Mary P; Aasly, Jan O; LeWitt, Peter A

2016-03-01

Leucine-rich repeat kinase 2 (LRRK2) gene mutations are the most common genetic cause of Parkinson's disease (PD). CSF specimens from LRRK2 + PD patients and healthy LRRK2 mutation carriers are, therefore, useful for biomarker studies. This study examined the hypothesis that differences are present between subjects with sporadic PD (sPD), PD carriers of LRRK2 mutations (LRRK2 + PD), healthy control subjects lacking LRRK2 mutations (CTL), and LRRK2 mutation-carrying healthy controls (LRRK2 + CTL) for CSF concentrations of six potential PD biomarkers. Two of these proteins, nuclear factor (erythroid-derived 2)-like 2 ("Nrf2") and heat shock 70 kDa protein 8 ("HSPA8"), were detected in preliminary ELISAs, then measured in a larger cohort (60 sPD, 10 LRRK2 + PD, 23 CTL, 31 LRRK2 + CTL). No statistically significant differences were found between the groups (Nrf2 p = 0.13, HSPA8 p = 0.21). Nrf2 concentrations in LRRK2 + PD subjects were strongly positively associated with Unified Parkinson's Disease Rating Scale (UPDRS) total and motor scores [Spearman rho = 0.77 (p = 0.012) and 0.83 (p = 0.005)] and negatively associated with Montreal Cognitive Assessment (MoCA) scores (rho = -0.57; p = 0.11). Partial correlation coefficient calculations indicated that disease duration contributed to the associations of Nrf2 levels with UPDRS scores and with MoCA scores in this group. While CSF Nrf2 and HSPA8 do not appear to offer diagnostic biomarkers for PD, the associations between Nrf2 levels and UPDRS scores in LRRK2 + PD patients merit further investigation.

Non-exercise physical activity attenuates motor symptoms in Parkinson disease independent from nigrostriatal degeneration

PubMed Central

Snider, Jon; Müller, Martijn L.T.M; Kotagal, Vikas; Koeppe, Robert A; Scott, Peter J.H.; Frey, Kirk A; Albin, Roger L.; Bohnen, Nicolaas I.

2015-01-01

Objective To investigate the relationship between time spent in non-exercise and exercise physical activity and severity of motor functions in Parkinson disease (PD). Background Increasing motor impairments of PD incline many patients to a sedentary lifestyle. We investigated the relationship between duration of both non-exercise and exercise physical activity over a 4-week period using the Community Health Activities Model Program for Seniors (CHAMPS) questionnaire and severity of clinical motor symptoms in PD. We accounted for the magnitude of nigrostriatal degeneration. Methods Cross-sectional study. PD subjects, n=48 (40M); 69.4±7.4 (56–84) years old; 8.4±4.2 (2.5–20) years motor disease duration, mean UPDRS motor score 27.5 ± 10.3 (7–53) and mean MMSE score 28.4 ± 1.9 (22–30) underwent [11C]dihydrotetrabenazine (DTBZ) PET imaging to assess nigrostriatal denervation and completed the CHAMPS questionnaire and clinical assessment. Results Bivariate correlations showed an inverse relationship between motor UPDRS severity scores and duration of non-exercise physical activity (R= −0.37, P=0.0099) but not with duration of exercise physical activity (R= −0.05, P= 0.76) over 4 weeks. Multiple regression analysis using UPDRS motor score as outcome variable demonstrated a significant regressor effect for duration of non-exercise physical activity (F=6.15, P=0.017) while accounting for effects of nigrostriatal degeneration (F=4.93, P=0.032), levodopa-equivalent dose (LED; F=1.07, P=0.31), age (F=4.37, P=0.043) and duration of disease (F=1.46, P=0.23; total model (F=5.76, P=0.0004). Conclusions Non-exercise physical activity is a correlate of motor symptom severity in PD independent of the magnitude of nigrostriatal degeneration. Non-exercise physical activity may have positive effects on functional performance in PD. PMID:26330028

Rotigotine for nocturnal hypokinesia in Parkinson's disease: Quantitative analysis of efficacy from a randomized, placebo-controlled trial using an axial inertial sensor.

PubMed

Bhidayasiri, Roongroj; Sringean, Jirada; Chaiwong, Suchapit; Anan, Chanawat; Penkeaw, Nuntiwat; Leaknok, Amarinee; Boonpang, Kamolwan; Saksornchai, Karn; Rattanachaisit, Watchara; Thanawattano, Chusak; Jagota, Priya

2017-11-01

Nocturnal hypokinesia is a common symptom in Parkinson's disease (PD), negatively affecting quality of life of both patients and caregivers. However, evidence-based treatment strategies are limited. To evaluate the efficacy of rotigotine transdermal patch, using a wearable sensor, in the management of nocturnal immobility. 34 PD subjects with nocturnal immobility were randomized to receive rotigotine transdermal patch (mean ± SD of 10.46 ± 4.63 mg/24 h, n = 17) or placebo patch (n = 17). Treatment was titrated to an optimal dose over 1-8 weeks, then maintained for 4 weeks. Primary endpoints were objective parameters assessing axial rotation measured using an axial inertial sensor (the NIGHT-Recorder) over two nights at the patients' home. Scale-based assessments were also performed. There was a significant difference, in favor of rotigotine, in change from baseline score in the number of turns in bed (ANCOVA, p = 0.001), and degree of axial turn (p = 0.042). These objective improvements were mirrored by significantly greater improvements in clinical scale-based assessments, including the Unified Parkinson's Disease Rating Scale (UPDRS) total scores (p = 0.009), UPDRS-motor scores (p < 0.001), UPDRS-axial scores (p = 0.01), the Modified Parkinson's Disease Sleep Scale (p < 0.001), the Nocturnal Akinesia Dystonia and Cramp Scale (p = 0.003) and the eight-item PD Questionnaire (PDQ-8) scores (p = 0.01) from baseline to end of treatment in patients given rotigotine compared to placebo. We show that the rotigotine patch provides a significant improvement in nocturnal symptoms as assessed using both objective measures and clinical rating scales. The study demonstrates the feasibility of using wearable sensors to record objective outcomes in PD-related clinical trials. Copyright © 2017 Elsevier Ltd. All rights reserved.

Multiple-source current steering in subthalamic nucleus deep brain stimulation for Parkinson's disease (the VANTAGE study): a non-randomised, prospective, multicentre, open-label study.

PubMed

Timmermann, Lars; Jain, Roshini; Chen, Lilly; Maarouf, Mohamed; Barbe, Michael T; Allert, Niels; Brücke, Thomas; Kaiser, Iris; Beirer, Sebastian; Sejio, Fernando; Suarez, Esther; Lozano, Beatriz; Haegelen, Claire; Vérin, Marc; Porta, Mauro; Servello, Domenico; Gill, Steven; Whone, Alan; Van Dyck, Nic; Alesch, Francois

2015-07-01

High-frequency deep brain stimulation (DBS) with a single electrical source is effective for motor symptom relief in patients with Parkinson's disease. We postulated that a multiple-source, constant-current device that permits well defined distribution of current would lead to motor improvement in patients with Parkinson's disease. We did a prospective, multicentre, non-randomised, open-label intervention study of an implantable DBS device (the VANTAGE study) at six specialist DBS centres at universities in six European countries. Patients were judged eligible if they were aged 21-75 years, had been diagnosed with bilateral idiopathic Parkinson's disease with motor symptoms for more than 5 years, had a Hoehn and Yahr score of 2 or greater, and had a Unified Parkinson's disease rating scale part III (UPDRS III) score in the medication-off state of more than 30, which improved by 33% or more after a levodopa challenge. Participants underwent bilateral implantation in the subthalamic nucleus of a multiple-source, constant-current, eight-contact, rechargeable DBS system, and were assessed 12, 26, and 52 weeks after implantation. The primary endpoint was the mean change in UPDRS III scores (assessed by site investigators who were aware of the treatment assignment) from baseline (medication-off state) to 26 weeks after first lead implantation (stimulation-on, medication-off state). This study is registered with ClinicalTrials.gov, number NCT01221948. Of 53 patients enrolled in the study, 40 received a bilateral implant in the subthalamic nucleus and their data contributed to the primary endpoint analysis. Improvement was noted in the UPDRS III motor score 6 months after first lead implantation (mean 13·5 [SD 6·8], 95% CI 11·3-15·7) compared with baseline (37·4 [8·9], 34·5-40·2), with a mean difference of 23·8 (SD 10·6; 95% CI 20·3-27·3; p<0·0001). One patient died of pneumonia 24 weeks after implantation, which was judged to be unrelated to the procedure. 125 adverse events were reported, the most frequent of which were dystonia, speech disorder, and apathy. 18 serious adverse events were recorded, three of which were attributed to the device or procedure (one case each of infection, migration, and respiratory depression). All serious adverse events resolved without residual effects and stimulation remained on during the study. The multiple-source, constant-current, eight-contact DBS system suppressed motor symptoms effectively in patients with Parkinson's disease, with an acceptable safety profile. Future trials are needed to investigate systematically the potential benefits of this system on postoperative outcome and its side-effects. Boston Scientific. Copyright © 2015 Elsevier Ltd. All rights reserved.

Association of GBA Mutations and the E326K Polymorphism With Motor and Cognitive Progression in Parkinson Disease

PubMed Central

Davis, Marie Y.; Johnson, Catherine O.; Leverenz, James B.; Weintraub, Daniel; Trojanowski, John Q.; Chen-Plotkin, Alice; Van Deerlin, Vivianna M.; Quinn, Joseph F.; Chung, Kathryn A.; Peterson-Hiller, Amie L.; Rosenthal, Liana S.; Dawson, Ted M.; Albert, Marilyn S.; Goldman, Jennifer G.; Stebbins, Glenn T.; Bernard, Bryan; Wszolek, Zbigniew K.; Ross, Owen A.; Dickson, Dennis W.; Eidelberg, David; Mattis, Paul J.; Niethammer, Martin; Yearout, Dora; Hu, Shu-Ching; Cholerton, Brenna A.; Smith, Megan; Mata, Ignacio F.; Montine, Thomas J.; Edwards, Karen L.; Zabetian, Cyrus P.

2016-01-01

IMPORTANCE Parkinson disease (PD) is heterogeneous in symptom manifestation and rate of progression. Identifying factors that influence disease progression could provide mechanistic insight, improve prognostic accuracy, and elucidate novel therapeutic targets. OBJECTIVE To determine whether GBA mutations and the E326K polymorphism modify PD symptom progression. DESIGN, SETTING, AND PARTICIPANTS The entire GBA coding region was screened for mutations and E326K in 740 patients with PD enrolled at 7 sites from the PD Cognitive Genetics Consortium. Detailed longitudinal motor and cognitive assessments were performed with patients in the on state. MAIN OUTCOMES AND MEASURES Linear regression was used to test for an association between GBA genotype and motor progression, with the Movement Disorder Society–sponsored version of the Unified Parkinson’s Disease Rating Scale Part III (MDS-UPDRS III) score at the last assessment as the outcome and GBA genotype as the independent variable, with adjustment for levodopa equivalent dose, sex, age, disease duration, MDS-UPDRS III score at the first assessment, duration of follow-up, and site. Similar methods were used to examine the association between genotype and tremor and postural instability and gait difficulty (PIGD) scores. To examine the effect of GBA genotype on cognitive progression, patients were classified into those with conversion to mild cognitive impairment or dementia during the study (progression) and those without progression. The association between GBA genotype and progression status was then tested using logistic regression, adjusting for sex, age, disease duration, duration of follow-up, years of education, and site. RESULTS Of the total sample of 733 patients who underwent successful genotyping, 226 (30.8%) were women and 507 (69.2%) were men (mean [SD] age, 68.1 [8.8] years). The mean (SD) duration of follow-up was 3.0 (1.7) years. GBA mutations (β = 4.65; 95% CI, 1.72–7.58; P = .002), E326K (β = 3.42; 95% CI, 0.66–6.17; P = .02), and GBA variants combined as a single group (β = 4.01; 95% CI, 1.95–6.07; P = 1.5 × 10−4) were associated with a more rapid decline in MDS-UPDRS III score. Combined GBA variants (β = 0.38; 95% CI, 0.23–0.53; P = .01) and E326K (β = 0.64; 95% CI, 0.43–0.86; P = .002) were associated with faster progression in PIGD scores, but not in tremor scores. A significantly higher proportion of E326K carriers (10 of 21 [47.6%]; P = .01) and GBA variant carriers (15 of 39 [38.5%]; P = .04) progressed to mild cognitive impairment or dementia. CONCLUSIONS AND RELEVANCE GBA variants predict a more rapid progression of cognitive dysfunction and motor symptoms in patients with PD, with a greater effect on PIGD than tremor. Thus, GBA variants influence the heterogeneity in symptom progression observed in PD. PMID:27571329

Ambulatory monitoring of activities and motor symptoms in Parkinson's disease.

PubMed

Zwartjes, Daphne G M; Heida, Tjitske; van Vugt, Jeroen P P; Geelen, Jan A G; Veltink, Peter H

2010-11-01

Ambulatory monitoring of motor symptoms in Parkinsons disease (PD) can improve our therapeutic strategies, especially in patients with motor fluctuations. Previously published monitors usually assess only one or a few basic aspects of the cardinal motor symptoms in a laboratory setting. We developed a novel ambulatory monitoring system that provides a complete motor assessment by simultaneously analyzing current motor activity of the patient (e.g. sitting, walking) and the severity of many aspects related to tremor, bradykinesia, and hypokinesia. The monitor consists of a set of four inertial sensors. Validity of our monitor was established in seven healthy controls and six PD patients treated with deep brain stimulation (DBS) of the subthalamic nucleus. Patients were tested at three different levels of DBS treatment. Subjects were monitored while performing different tasks, including motor tests of the Unified Parkinsons Disease Rating Scale (UPDRS). Output of the monitor was compared to simultaneously recorded videos. The monitor proved very accurate in discriminating between several motor activities. Monitor output correlated well with blinded UPDRS ratings during different DBS levels. The combined analysis of motor activity and symptom severity by our PD monitor brings true ambulatory monitoring of a wide variety of motor symptoms one step closer..

Variability in Cadence During Forced Cycling Predicts Motor Improvement in Individuals With Parkinson’s Disease

PubMed Central

Ridgel, Angela L.; Abdar, Hassan Mohammadi; Alberts, Jay L.; Discenzo, Fred M.; Loparo, Kenneth A.

2014-01-01

Variability in severity and progression of Parkinson’s disease symptoms makes it challenging to design therapy interventions that provide maximal benefit. Previous studies showed that forced cycling, at greater pedaling rates, results in greater improvements in motor function than voluntary cycling. The precise mechanism for differences in function following exercise is unknown. We examined the complexity of biomechanical and physiological features of forced and voluntary cycling and correlated these features to improvements in motor function as measured by the Unified Parkinson’s Disease Rating Scale (UPDRS). Heart rate, cadence, and power were analyzed using entropy signal processing techniques. Pattern variability in heart rate and power were greater in the voluntary group when compared to forced group. In contrast, variability in cadence was higher during forced cycling. UPDRS Motor III scores predicted from the pattern variability data were highly correlated to measured scores in the forced group. This study shows how time series analysis methods of biomechanical and physiological parameters of exercise can be used to predict improvements in motor function. This knowledge will be important in the development of optimal exercise-based rehabilitation programs for Parkinson’s disease. PMID:23144045

Comparison of chocolate to cacao-free white chocolate in Parkinson's disease: a single-dose, investigator-blinded, placebo-controlled, crossover trial.

PubMed

Wolz, Martin; Schleiffer, Christine; Klingelhöfer, Lisa; Schneider, Christine; Proft, Florian; Schwanebeck, Uta; Reichmann, Heinz; Riederer, Peter; Storch, Alexander

2012-11-01

A previous questionnaire study suggests an increased chocolate consumption in Parkinson's disease (PD). The cacao ingredient contains caffeine analogues and biogenic amines, such as β-phenylethylamine, with assumed antiparkinsonian effects. We thus tested the effects of 200 g of chocolate containing 80 % of cacao on UPDRS motor score after 1 and 3 h in 26 subjects with moderate non-fluctuating PD in a mono-center, single-dose, investigator-blinded crossover study using cacao-free white chocolate as placebo comparator. At 1 h after chocolate intake, mean UPDRS motor scores were mildly decreased compared to baseline in both treatments with significant results only for dark chocolate [-1.3 (95 % CI 0.18-2.52, RMANOVA F = 4.783, p = 0.013¸ Bonferroni p = 0.021 for 1 h values)]. A 2 × 2-cross-over analysis revealed no significant differences between both treatments [-0.54 ± 0.47 (95 % CI -1.50 to 0.42), p = 0.258]. Similar results were obtained at 3 h after intake. β-phenylethylamine blood levels were unaltered. Together, chocolate did not show significant improvement over white cacao-free chocolate in PD motor function.

Predictive model for falling in Parkinson disease patients.

PubMed

Custodio, Nilton; Lira, David; Herrera-Perez, Eder; Montesinos, Rosa; Castro-Suarez, Sheila; Cuenca-Alfaro, Jose; Cortijo, Patricia

2016-12-01

Falls are a common complication of advancing Parkinson's disease (PD). Although numerous risk factors are known, reliable predictors of future falls are still lacking. The aim of this study was to develop a multivariate model to predict falling in PD patients. Prospective cohort with forty-nine PD patients. The area under the receiver-operating characteristic curve (AUC) was calculated to evaluate predictive performance of the purposed multivariate model. The median of PD duration and UPDRS-III score in the cohort was 6 years and 24 points, respectively. Falls occurred in 18 PD patients (30%). Predictive factors for falling identified by univariate analysis were age, PD duration, physical activity, and scores of UPDRS motor, FOG, ACE, IFS, PFAQ and GDS ( p -value < 0.001), as well as fear of falling score ( p -value = 0.04). The final multivariate model (PD duration, FOG, ACE, and physical activity) showed an AUC = 0.9282 (correctly classified = 89.83%; sensitivity = 92.68%; specificity = 83.33%). This study showed that our multivariate model have a high performance to predict falling in a sample of PD patients.

Design of the Park-in-Shape study: a phase II double blind randomized controlled trial evaluating the effects of exercise on motor and non-motor symptoms in Parkinson's disease.

PubMed

van der Kolk, Nicolien M; Overeem, Sebastiaan; de Vries, Nienke M; Kessels, Roy P C; Donders, Rogier; Brouwer, Marc; Berg, Daniela; Post, Bart; Bloem, Bas R

2015-04-16

Parkinson's disease (PD) is a neurodegenerative disorder with a wide range of motor and non-motor symptoms. Despite optimal medical management, PD still results in a high disability rate and secondary complications and many patients lead a sedentary lifestyle, which in turn is also associated with a higher co-morbidity and mortality. Exercise has been explored as a strategy to reduce secondary complications and results suggests that it not only provides general health benefits, but may also provide symptomatic relief. If this holds true exercise would be a very attractive addition to the therapeutic arsenal in PD. The supportive evidence remains incomplete. Here, we describe the design of the Park-in-Shape study, which primarily aims to evaluate whether aerobic exercise affords clinically relevant improvements in motor symptoms in sedentary PD patients. A specific new element is the introduction of gaming to optimize compliance to the exercise intervention. The Park-in-Shape study is a randomized controlled, assessor- and patient-blinded single center study. Two parallel groups will include a total of 130 patients, receiving either aerobic exercise on a home trainer equipped with gaming elements ("exergaming"), or a non-aerobic intervention (stretching, flexibility and relaxation exercises). Both groups are supported by a specifically designed motivational app that uses gaming elements to stimulate patients to exercise and rewards them after having completed the exercise. Both interventions are delivered at home at least 3 times a week for 30-45 minutes during 6 months. Eligible patients are community-dwelling, sedentary patients diagnosed with mild-moderate PD. The primary outcome is the MDS-UPDRS motor score (tested in the off state) after 6 months. Secondary outcomes include various motor and non-motor symptoms, quality of life, physical fitness, and adherence. This Park-in-Shape study is anticipated to answer the question whether high intensity aerobic exercise combined with gaming elements ("exergaming") provides symptomatic relief in PD. Strong elements include the double-blinded randomized controlled trial design, the MDS-UPDRS as valid primary outcome, the large sample size and unique combination of home-based pure aerobic exercise combined with gaming elements and motivational aspects. Dutch trial register NTR4743.

A randomised controlled cross-over trial of aerobic training versus Qigong in advanced Parkinson's disease.

PubMed

Burini, D; Farabollini, B; Iacucci, S; Rimatori, C; Riccardi, G; Capecci, M; Provinciali, L; Ceravolo, M G

2006-09-01

To investigate the effects of an aerobic training in subjects with Parkinson's disease (PD) as compared to a medical Chinese exercise (Qigong). randomized controlled trial with a cross over design. PD out-patients referred to a Neurorehabilitation facility for the management of motor disability. 26 PD patients in Hoehn and Yahr stage II to III under stable medication were randomly allocated to either Group AT1+QG2 (receiving 20 aerobic training sessions followed by 20 ''Qigong'' group sessions with 2 month interval between the interventions), or Group QG1+AT2 (performing the same treatments with an inverted sequence). clinical effects of treatment were sought through the Unified Parkinson's Disease Rating Scale (UPDRS), Brown's Disability Scale (B'DS), six-Minute Walking Test (6MWT), Borg scale for breathlessness, Beck Depression Inventory (BDI) and Parkinson's Disease Questionnaire-39 items (PDQ-39). A spirometry test and maximum cardiopulmonary exercise test (CPET) were also performed to determine the pulmonary function, the metabolic and cardio-respiratory requests at rest and under exercise. All measures were taken immediately before and at the completion of each treatment phase. The statistical analysis focusing on the evolution of motor disability and quality of life revealed a significant interaction effect between group and time for the 6MWT (time x group effect: F: 5.4 P=0.002) and the Borg scale (time x group effect: F: 4.2 P=0.009). Post hoc analysis showed a significant increase in 6MWT and a larger decrease in Borg score after aerobic training within each subgroup, whereas no significant changes were observed during Qigong. No significant changes over time were detected through the analysis of UPDRS, B'DS, BDI and PDQ-39 scores. The analysis of cardiorespiratory parameters showed significant interaction effects between group and time for the Double Productpeak (time x group effect: F: 7.7 P=0.0003), the VO(2peak) (time x group effect: F: 4.8 P=0.007), and the VO(2)/kg ratio (time x group effect: F: 4.3 P=0.009), owing to their decrease after aerobic training to an extent that was never observed after Qigong treatment. Aerobic training exerts a significant impact on the ability of moderately disabled PD patients to cope with exercise, although it does not improve their self-sufficiency and quality of life.

A computer vision framework for finger-tapping evaluation in Parkinson's disease.

PubMed

Khan, Taha; Nyholm, Dag; Westin, Jerker; Dougherty, Mark

2014-01-01

The rapid finger-tapping test (RFT) is an important method for clinical evaluation of movement disorders, including Parkinson's disease (PD). In clinical practice, the naked-eye evaluation of RFT results in a coarse judgment of symptom scores. We introduce a novel computer-vision (CV) method for quantification of tapping symptoms through motion analysis of index-fingers. The method is unique as it utilizes facial features to calibrate tapping amplitude for normalization of distance variation between the camera and subject. The study involved 387 video footages of RFT recorded from 13 patients diagnosed with advanced PD. Tapping performance in these videos was rated by two clinicians between the symptom severity levels ('0: normal' to '3: severe') using the unified Parkinson's disease rating scale motor examination of finger-tapping (UPDRS-FT). Another set of recordings in this study consisted of 84 videos of RFT recorded from 6 healthy controls. These videos were processed by a CV algorithm that tracks the index-finger motion between the video-frames to produce a tapping time-series. Different features were computed from this time series to estimate speed, amplitude, rhythm and fatigue in tapping. The features were trained in a support vector machine (1) to categorize the patient group between UPDRS-FT symptom severity levels, and (2) to discriminate between PD patients and healthy controls. A new representative feature of tapping rhythm, 'cross-correlation between the normalized peaks' showed strong Guttman correlation (μ2=-0.80) with the clinical ratings. The classification of tapping features using the support vector machine classifier and 10-fold cross validation categorized the patient samples between UPDRS-FT levels with an accuracy of 88%. The same classification scheme discriminated between RFT samples of healthy controls and PD patients with an accuracy of 95%. The work supports the feasibility of the approach, which is presumed suitable for PD monitoring in the home environment. The system offers advantages over other technologies (e.g. magnetic sensors, accelerometers, etc.) previously developed for objective assessment of tapping symptoms. Copyright © 2013 Elsevier B.V. All rights reserved.

Evaluation of rotigotine transdermal patch for the treatment of apathy and motor symptoms in Parkinson's disease.

PubMed

Hauser, Robert A; Slawek, Jaroslaw; Barone, Paolo; Dohin, Elisabeth; Surmann, Erwin; Asgharnejad, Mahnaz; Bauer, Lars

2016-06-07

This multicenter, double-blind, placebo-controlled study assessed the efficacy of rotigotine transdermal patch on apathy and motor symptoms in patients with Parkinson's disease (PD). Patients with PD-associated apathy (Unified Parkinson's Disease Rating Scale [UPDRS] I item 4 [motivation] ≥2 and patient-rated Apathy Scale [AS] ≥14) were randomized 1:1:1 to "low-dose" rotigotine (≤6 mg/24 h for early PD [those not receiving levodopa] or ≤8 mg/24 h for advanced PD [those receiving levodopa]), "high-dose" rotigotine (≤8 mg/24 h for early PD or ≤16 mg/24 h for advanced PD), or placebo, and maintained at optimal/maximal dose for 12 weeks. Coprimary efficacy variables were: change from baseline to End of Maintenance in patient-rated AS and UPDRS II + III total score. Recruitment was stopped after an interim futility analysis; therefore, all p values are exploratory. Of 122 patients randomized, 81.1 % completed the study (placebo, n = 32/40 [80.0 %]; low-dose rotigotine, n = 30/41 [73.2 %]; high-dose rotigotine, n = 37/41 [90.2 %]). No treatment difference was observed in the change in patient-rated AS (least squares mean [95 % confidence interval (CI)] difference: low-dose, 0.04 [-2.42, 2.50], p =0.977; high-dose, -0.22 [-2.61, 2.18], p = 0.859). Rotigotine improved UPDRS II + III total scores versus placebo (least squares mean [95 % CI] treatment difference: low-dose, -7.29 [-12.30, -2.28], p = 0.005; high-dose, -6.06 [-10.90, -1.21], p = 0.015), and the "mood/apathy" domain of the Non-Motor Symptom Scale as rated by the investigator (secondary outcome). The most frequent adverse events in rotigotine-treated patients were application site reactions, somnolence, and nausea. Rotigotine did not improve PD-associated apathy as rated by the patient but provided clinically relevant improvement in motor control and activities of daily living. ClinicalTrials.gov identifier NCT01782222 . Trial registration date: January 30, 2013.

TCH346 as a neuroprotective drug in Parkinson's disease: a double-blind, randomised, controlled trial.

PubMed

Olanow, C Warren; Schapira, Anthony H V; LeWitt, Peter A; Kieburtz, Karl; Sauer, Dirk; Olivieri, Gianfranco; Pohlmann, Harald; Hubble, Jean

2006-12-01

There is an important unmet medical need in Parkinson's disease for a neuroprotective treatment that slows or stops disease progression. TCH346 is a potent anti-apoptotic drug that protects against loss of dopaminergic neurons in laboratory models. Our aim was to assess TCH346 as a neuroprotective drug in patients with Parkinson's disease. Patients presenting at 45 international movement disorder clinics with early untreated Parkinson's disease were assessed as part of this parallel-group, double-blind, randomised controlled trial. 301 eligible patients were randomly assigned 12-18 months' treatment with TCH346 at a daily dose of 0.5 mg (n=78), 2.5 mg (n=79), or 10 mg (n=73), or placebo (n=71), followed by a 4 week washout period. The primary outcome measure was time to development of a disability requiring dopaminergic treatment. Secondary outcome measures were the annual rate of change in the unified Parkinson's disease rating scale (UPDRS) and the PDQ-39, a measure of quality of life. Analyses were by intention-to-treat. This study is pending registration with . 255 patients completed the study. TCH346 did not differ from placebo for any of the study outcomes. Treatment was needed in 26 (34%) patients in the TCH346 0.5 mg group, 30 (38%) in the TCH346 2.5 mg group, 24 (33%) in the TCH346 10 mg group, and 23 (32%) in the placebo group. There were no significant differences between groups. There were no differences between groups in the annual change in the UPDRS or PDQ-39 either. Few patients withdrew because of adverse events and none was judged to be related to the study intervention. TCH346 did not show evidence of a neuroprotective effect. The discrepancy between the preclinical promise of TCH346 and the clinical outcome could have arisen because of the use of laboratory models that do not accurately reflect the pathogenesis of Parkinson's disease, the doses of study drug used, insensitive clinical endpoints, and the patient population selected for study.

Long-term effect of low frequency stimulation of STN on dysphagia, freezing of gait and other motor symptoms in PD.

PubMed

Xie, Tao; Bloom, Lisa; Padmanaban, Mahesh; Bertacchi, Breanna; Kang, Wenjun; MacCracken, Ellen; Dachman, Abraham; Vigil, Julie; Satzer, David; Zadikoff, Cindy; Markopoulou, Katerina; Warnke, Peter; Kang, Un Jung

2018-04-13

To evaluate the long-term effect of 60 Hz stimulation of the subthalamic nucleus (STN) on dysphagia, freezing of gait (FOG) and other motor symptoms in patients with Parkinson's disease (PD) who have FOG at the usual 130 Hz stimulation. This is a prospective, sequence randomised, crossover, double-blind study. PD patients with medication refractory FOG at 130 Hz stimulation of the STN were randomised to the sequences of 130 Hz, 60 Hz or deep brain stimulation off to assess swallowing function (videofluoroscopic evaluation and swallowing questionnaire), FOG severity (stand-walk-sit test and FOG questionnaire) and motor function (Unified PD Rating Scale, Part III motor examination (UPDRS-III)) at initial visit (V1) and follow-up visit (V2, after being on 60 Hz stimulation for an average of 14.5 months), in their usual medications on state. The frequency of aspiration events, perceived swallowing difficulty and FOG severity at 60 Hz compared with 130 Hz stimulation at V2, and their corresponding changes at V2 compared with V1 at 60 Hz were set as primary outcomes, with similar comparisons in UPDRS-III and its subscores as secondary outcomes. All 11 enrolled participants completed V1 and 10 completed V2. We found the benefits of 60 Hz stimulation compared with 130 Hz in reducing aspiration frequency, perceived swallowing difficulty, FOG severity, bradykinesia and overall axial and motor symptoms at V1 and persistent benefits on all of them except dysphagia at V2, with overall decreasing efficacy when comparing V2 to V1. The 60 Hz stimulation, when compared with 130 Hz, has long-term benefits on reducing FOG, bradykinesia and overall axial and motor symptoms except dysphagia, although the overall benefits decrease with long-term use. NCT02549859;Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Effect and Potential Mechanism of Electroacupuncture Add-On Treatment in Patients with Parkinson's Disease

PubMed Central

Wang, Fang; Sun, Li; Zhang, Xiao-zhe; Jia, Jun; Liu, Zhuo; Huang, Xi-yan; Yu, Shu-yang; Zuo, Li-jun; Cao, Chen-jie; Wang, Xiao-min; Zhang, Wei

2015-01-01

Objectives. To explore effectiveness and mechanisms of electroacupuncture (EA) add-on treatment in Parkinson's disease (PD) patients. Methods. Fifty PD patients were randomly assigned to drug plus EA (D + EA) group and drug alone (D) group. Subjects in D + EA group received stimulation in points of bilateral fengfu, fengchi, hegu, and central dazhui. Participants were evaluated by scales for motor and nonmotor symptoms. Levels of neuroinflammatory factors and neurotransmitters in serum were detected. Results. EA add-on treatment remarkably reduced scores of Unified Parkinson's Disease Rating Scale (UPDRS) III and its subitems of tremor, rigidity, and bradykinesia and conspicuously decreased UPDRS III scores in patients with bradykinesia-rigidity and mixed types and mild severity. Depression and sleep disturbances were eased, which were reflected by decreased scores of Hamilton Depression Rating Scale, Pittsburgh Sleep Quality Index, and elevated noradrenaline level. Effects of EA add-on treatment on motor symptoms and sleep disturbances were superior to drug alone treatment, markedly improving life quality of PD patients. EA add-on treatment decreased nitric oxide level in serum. Conclusions. EA add-on treatment is effective on most motor symptoms and some nonmotor symptoms and is particularly efficacious in PD patients at early stage. Antineuroinflammation may be a mechanism of EA add-on treatment. PMID:26351515

Subthalamic nucleus stimulation does not influence basal glucose metabolism or insulin sensitivity in patients with Parkinson's disease.

PubMed

Lammers, Nicolette M; Sondermeijer, Brigitte M; Twickler, Th B Marcel; de Bie, Rob M; Ackermans, Mariëtte T; Fliers, Eric; Schuurman, P Richard; La Fleur, Susanne E; Serlie, Mireille J

2014-01-01

Animal studies have shown that central dopamine signaling influences glucose metabolism. As a first step to show this association in an experimental setting in humans, we studied whether deep brain stimulation (DBS) of the subthalamic nucleus (STN), which modulates the basal ganglia circuitry, alters basal endogenous glucose production (EGP) or insulin sensitivity in patients with Parkinson's disease (PD). We studied 8 patients with PD treated with DBS STN, in the basal state and during a hyperinsulinemic euglycemic clamp using a stable glucose isotope, in the stimulated and non-stimulated condition. We measured EGP, hepatic insulin sensitivity, peripheral insulin sensitivity (Rd), resting energy expenditure (REE), glucoregulatory hormones, and Parkinson symptoms, using the Unified Parkinson's Disease Rating Scale (UPDRS). Basal plasma glucose and EGP did not differ between the stimulated and non-stimulated condition. Hepatic insulin sensitivity was similar in both conditions and there were no significant differences in Rd and plasma glucoregulatory hormones between DBS on and DBS off. UPDRS was significantly higher in the non-stimulated condition. DBS of the STN in patients with PD does not influence basal EGP or insulin sensitivity. These results suggest that acute modulation of the motor basal ganglia circuitry does not affect glucose metabolism in humans.

Depression and care-dependency in Parkinson's disease: results from a nationwide study of 1449 outpatients.

PubMed

Riedel, O; Dodel, R; Deuschl, G; Klotsche, J; Förstl, H; Heuser, I; Oertel, W; Reichmann, H; Riederer, P; Trenkwalder, C; Wittchen, H-U

2012-06-01

Parkinson's disease (PD) is frequently compounded by neuropsychiatric complications, increasing disability. The combined effect of motor and mental status on care-dependency in PD outpatients is not well characterized. We conducted a cross-sectional study of 1449 PD outpatients. The assessment comprised the Montgomery-Asberg Depression Rating Scale (MADRS) and the diagnostic criteria for dementia. PD severity and treatment complications were rated using Hoehn and Yahr staging and the Unified Parkinson's Disease Rating Scale (UPDRS) IV. The acknowledged level of care-dependency was documented. Care-dependency was present in 18.3% of all patients. A total of 13.9% had dementia, 18.8% had depression, and 14.3% had both. Regression analyses revealed increasing effects of age, PD duration, and PD severity on care-dependency in all three mental-disorder subgroups with the strongest effects in patients with depression only. Depressed patients with antidepressive treatment still had significantly higher PD severity, higher MADRS and UPDRS-IV scores but were not more likely to be care-dependent than non-depressed patients. Older age, longer duration and increased severity of PD contribute to care-dependency in patients with untreated depression. Treatment of depression is associated with lower rates of care-dependency. Copyright © 2011 Elsevier Ltd. All rights reserved.

Short- and Long-Term Efficacy of Intensive Rehabilitation Treatment on Balance and Gait in Parkinsonian Patients: A Preliminary Study with a 1-Year Followup

PubMed Central

Bertotti, Gabriella; Uccellini, Davide; Boveri, Natalia; Rovescala, R.; Pezzoli, Gianni

2013-01-01

Parkinson's disease (PD) is a neurodegenerative disease in which gait and balance disturbances are relevant symptoms that respond poorly to pharmacological treatment. The aim of this study was to investigate whether a 4-week inpatient multidisciplinary intensive rehabilitation treatment (MIRT) is effective in improving balance and gait and whether improvements persist at a one-year followup. We studied 20 PD inpatients (stage 3 Hoehn-Yahr) who underwent a MIRT. Outcome measures were UPDRS items for balance (30), falls (13), and walk (29), Berg Balance Scale, six-minute walking test, Timed Up and Go Test, and Comfortable-Fast gait speeds. Patients were evaluated at admission, at the end of the 4-week treatment, and at a 1-year followup. Pharmacological therapy was unchanged during MIRT and follow-up. All outcome measures improved significantly at the end of treatment. At 1-year follow-up control, UPDRS walk and Comfortable-Fast gait speeds still maintained better values with respect to admission (P = 0.009, P = 0.03, and P = 0.02, resp.), while the remaining scales did not differ significantly. Our results demonstrate that the MIRT was effective in improving balance and gait and that the improvement in gait performances was partially maintained also after 1 year. PMID:23766927

Programming for Stimulation-Induced Transient Nonmotor Psychiatric Symptoms after Bilateral Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease

PubMed Central

Wu, Xi; Qiu, Yiqing; Simfukwe, Keith; Wang, Jiali; Chen, Jianchun

2017-01-01

Background Stimulation-induced transient nonmotor psychiatric symptoms (STPSs) are side effects following bilateral subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD) patients. We designed algorithms which (1) determine the electrode contacts that induce STPSs and (2) provide a programming protocol to eliminate STPS and maintain the optimal motor functions. Our objective is to test the effectiveness of these algorithms. Materials and Methods 454 PD patients who underwent programming sessions after STN-DBS implantations were retrospectively analyzed. Only STPS patients were enrolled. In these patients, the contacts inducing STPS were found and the programming protocol algorithms used. Results Eleven patients were diagnosed with STPS. Of these patients, two had four episodes of crying, and two had four episodes of mirthful laughter. In one patient, two episodes of abnormal sense of spatial orientation were observed. Hallucination episodes were observed twice in one patient, while five patients recorded eight episodes of hypomania. There were no statistical differences between the UPDRS-III under the final stimulation parameter (without STPS) and previous optimum UPDRS-III under the STPSs (p = 1.000). Conclusion The flow diagram used for determining electrode contacts that induce STPS and the programming protocol employed in the treatment of these symptoms are effective. PMID:28894620

Double-blind, randomized, controlled trial of rasagiline as monotherapy in early Parkinson's disease patients.

PubMed

Stern, Matthew B; Marek, Kenneth L; Friedman, Joseph; Hauser, Robert A; LeWitt, Peter A; Tarsy, Daniel; Olanow, C Warren

2004-08-01

Rasagiline (N-propargyl-1(R)-aminoindan) mesylate is a potent, selective, and irreversible monoamine oxidase-B inhibitor. This study was designed to evaluate the safety, tolerability, and preliminary efficacy of rasagiline monotherapy in early Parkinson's disease (PD) patients not receiving levodopa. The study was performed as a multicenter, parallel-group, double-blind, randomized, placebo-controlled, 10-week study. Fifty-six PD patients were randomly assigned to rasagiline mesylate 1, 2, or 4 mg once daily, or placebo. A 3-week dose-escalation period was followed by a 7-week maintenance phase. At week 10, the mean (+/-SE) changes from baseline in total Unified Parkinson's Disease Rating Scale (UPDRS) score were -1.8 (+/-1.3), -3.6 (+/-1.7), -3.6 (+/-1.2), and -0.5 (+/-0.8) in the rasagiline 1, 2, and 4 mg/day and placebo groups, respectively. Analysis of responders showed that 28% of patients (12 of 43) receiving rasagiline had an improvement in total UPDRS score of greater than 30%, compared with none of the patients receiving placebo (P < 0.05, Fisher's exact test). The frequency and types of adverse events reported by rasagiline-treated and placebo-treated patients were similar. These results suggest that rasagiline monotherapy is well tolerated and efficacious in early PD. Copyright 2004 Movement Disorder Society

Effect of Exercise on Motor and Nonmotor Symptoms of Parkinson's Disease

PubMed Central

Dashtipour, Khashayar; Johnson, Eric; Kani, Camellia; Kani, Kayvan; Hadi, Ehsan; Ghamsary, Mark; Pezeshkian, Shant; Chen, Jack J.

2015-01-01

Background. Novel rehabilitation strategies have demonstrated potential benefits for motor and non-motor symptoms of Parkinson's disease (PD). Objective. To compare the effects of Lee Silverman Voice Therapy BIG (LSVT BIG therapy) versus a general exercise program (combined treadmill plus seated trunk and limb exercises) on motor and non-motor symptoms of PD. Methods. Eleven patients with early-mid stage PD participated in the prospective, double-blinded, randomized clinical trial. Both groups received 16 one-hour supervised training sessions over 4 weeks. Outcome measures included the Unified Parkinson's Disease Rating Scale (UPDRS), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) and Modified Fatigue Impact Scale (MFIS). Five patients performed general exercise and six patients performed LSVT BIG therapy. Post-intervention evaluations were conducted at weeks 4, 12 and 24. Results. The combined cohort made improvements at all follow-up evaluations with statistical significance for UPDRS total and motor, BDI, and MFIS (P < 0.05). Conclusion. This study demonstrated positive effects of general exercise and LSVT BIG therapy on motor and non-motor symptoms of patients with PD. Our results suggest that general exercise may be as effective as LSVT BIG therapy on symptoms of PD for patients not able to readily access outpatient LSVT BIG therapy. PMID:25722915

Association of a neuronal nitric oxide synthase gene polymorphism with levodopa-induced dyskinesia in Parkinson's disease.

PubMed

Santos-Lobato, Bruno Lopes; Borges, Vanderci; Ferraz, Henrique Ballalai; Mata, Ignacio Fernandez; Zabetian, Cyrus P; Tumas, Vitor

2018-04-01

Levodopa-induced dyskinesia (LID) is a common complication of advanced Parkinson's disease (PD). PD physiopathology is associated with dopaminergic and non-dopaminergic pathways, including the nitric oxide system. The present study aims to examine the association of a neuronal nitric oxide synthase gene (NOS1) single nucleotide polymorphism (rs2682826) with LID in PD patients. We studied 186 PD patients using levodopa. The presence of LID was defined as a MDS-UPDRS Part IV score ≥1 on item 4.1. We tested for association between NOS1 rs2682826 and the presence, daily frequency, and functional impact of LID using regression models, adjusting for important covariates. There was no significant association between genotype and any of the LID-related variables examined. Our results suggest that this NOS1 polymorphism does not contribute to LID susceptibility or severity. However, additional studies that include a comprehensive set of NOS1 variants will be needed to fully define the role of this gene in LID. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparison of strength training, aerobic training, and additional physical therapy as supplementary treatments for Parkinson's disease: pilot study.

PubMed

Carvalho, Alessandro; Barbirato, Dannyel; Araujo, Narahyana; Martins, Jose Vicente; Cavalcanti, Jose Luiz Sá; Santos, Tony Meireles; Coutinho, Evandro S; Laks, Jerson; Deslandes, Andrea C

2015-01-01

Physical rehabilitation is commonly used in patients with Parkinson's disease (PD) to improve their health and alleviate the symptoms. We compared the effects of three programs, strength training (ST), aerobic training (AT), and physiotherapy, on motor symptoms, functional capacity, and electroencephalographic (EEG) activity in PD patients. Twenty-two patients were recruited and randomized into three groups: AT (70% of maximum heart rate), ST (80% of one repetition maximum), and physiotherapy (in groups). Subjects participated in their respective interventions twice a week for 12 weeks. The assessments included measures of disease symptoms (Unified Parkinson's Disease Rating Scale [UPDRS]), functional capacity (Senior Fitness Test), and EEG before and after 12 weeks of intervention. The PD motor symptoms (UPDRS-III) in the group of patients who performed ST and AT improved by 27.5% (effect size [ES]=1.25, confidence interval [CI]=-0.11, 2.25) and 35% (ES=1.34, CI=-0.16, 2.58), respectively, in contrast to the physiotherapy group, which showed a 2.9% improvement (ES=0.07, CI=-0.85, 0.99). Furthermore, the functional capacity of all three groups improved after the intervention. The mean frequency of the EEG analysis mainly showed the effect of the interventions on the groups (F=11.50, P=0.0001). ST and AT in patients with PD are associated with improved outcomes in disease symptoms and functional capacity.

CONTRIBUTION OF AXIAL MOTOR IMPAIRMENT TO PHYSICAL INACTIVITY IN PARKINSON'S DISEASE

PubMed Central

Bryant, Mon S; Hou, Jyhgong Gabriel; Collins, Robert L; Protas, Elizabeth J

2015-01-01

Objective To investigate the relationships between motor symptoms of Parkinson’s disease (PD) and activity limitations in persons with PD. Design/Methods Cross-sectional study of persons with mild to moderate PD (N=90). Associations among axial motor features, limb motor signs, the Physical Activity Scale for Elders (PASE), the ability to perform Activities of Daily Living (ADL) and level of ADL dependency were studied. A composite score of axial motor features included the following UPDRS items: speech, rigidity of the neck, arising from chair, posture, gait and postural stability. A composite score of limb motor signs included the following UPDRS items: tremor at rest of all extremities, action tremor, rigidity of all extremities, finger taps, hand movement, rapid alternating hand movements and foot tapping. Results Axial motor features of PD were significantly correlated with physical inactivity (p<.001), decreased ADL (p<.001) and increase in ADL dependency (p<.001). Limb motor signs significantly correlated with decreased ADL (p<.001) and level of ADL dependency (p=.035), but was not correlated with physical inactivity. After controlling for age, gender, disease duration and comorbidity, axial motor features contributed significantly to physical inactivity, decreased ADL and increase in ADL dependency, whereas the limb motor signs did not. Conclusions Axial motor impairment contributed to physical inactivity and decreased ability to perform ADLs in persons with PD. PMID:26368837

Assessment of mental health of carers according to patient stage of idiopathic Parkinson's disease.

PubMed

Olgun Yazar, Hülya; Yazar, Tamer; Yancar Demir, Esra; Cankaya, Soner; Enginyurt, Özgür

2018-05-30

In this study the aim was to collect data to assess the mental health of carers for patients with diagnosis of idiopathic Parkinson's disease (IPD) according to disease stage and to examine precautions to reduce the patient and disease load on carers. The study included 144 patients with staging according to modified Hoehn and Yahr criteria and 144 patient relatives who provided care support for patients every day, for some or all of the day, and who were over the age of 18 years and accepted participation in the research. Our prospective and cross-sectional study performed detailed neurological examination of patients, and after completing the 'Personal Information Form' with the interviewer every patient, with idiopathic Parkinson's disease (IPD) according to 'UK Brain Bank' diagnostic criteria, had the 'Unified Parkinson's Disease Rating Scale (UPDRS)' and 'Modified Hoehn and Yahr scale (HYS)' applied. Carers first completed the 'Personal Information Form' and then had the 'Short Symptom Inventory (SSI)' applied. As the stage of disease increased, the points for all sub-scales of the Short Symptom Inventory increased. With the parallel increase in disease scores and UPDRS stage scores, the points obtained by carers on the SSI sub-scales increased. This data shows that with progressing disease stage, the load on the carer increases and mental health begins to be disrupted.

Association between subthalamic nucleus deep brain stimulation and weight gain: Results of a case-control study.

PubMed

Strowd, Roy E; Herco, Maja; Passmore-Griffin, Leah; Avery, Bradley; Haq, Ihtsham; Tatter, Stephen B; Tate, Jessica; Siddiqui, Mustafa S

2016-01-01

To evaluate whether weight change in patients with Parkinson's disease (PD) is different in those undergoing deep brain stimulation (DBS) of the subthalamic nucleus (STN) compared to those not undergoing DBS. A retrospective case-control study was performed in PD patients who had undergone STN DBS (cases) compared to matched PD patients without DBS (controls). Demographic and clinical data including Unified Parkinson's Disease Rating Scale (UPDRS) motor scores were collected. Repeated measures mixed model regression was used to identify variables associated with weight gain. Thirty-five cases and 34 controls were identified. Baseline age, gender, diagnosis and weight were similar. Duration of diagnosis was longer in cases (6.3 vs 4.9 years, p=0.0015). At 21.3 months, cases gained 2.9 kg (+4.65%) while controls lost 1.8 kg (-3.05%, p<0.02). Postoperative UPDRS motor scores improved by 49% indicating surgical efficacy. Only younger age (p=0.0002) and DBS (p=0.008) were significantly associated with weight gain. In this case-control study, PD patients undergoing STN DBS experienced post-operative weight gain that was significantly different from the weight loss observed in non-DBS PD controls. Patients, especially overweight individuals, should be informed that STN DBS can result in weight gain. Copyright © 2015 Elsevier B.V. All rights reserved.

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

PubMed

Kim, Ji Sun; Youn, Jinyoung; Suh, Mee Kyung; Kim, Tae-Eun; Chin, Juhee; Park, Suyeon; Cho, Jin Whan

2015-11-01

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

Atlas-Independent, Electrophysiological Mapping of the Optimal Locus of Subthalamic Deep Brain Stimulation for the Motor Symptoms of Parkinson Disease.

PubMed

Conrad, Erin C; Mossner, James M; Chou, Kelvin L; Patil, Parag G

2018-05-23

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor symptoms of Parkinson disease (PD). However, motor outcomes can be variable, perhaps due to inconsistent positioning of the active contact relative to an unknown optimal locus of stimulation. Here, we determine the optimal locus of STN stimulation in a geometrically unconstrained, mathematically precise, and atlas-independent manner, using Unified Parkinson Disease Rating Scale (UPDRS) motor outcomes and an electrophysiological neuronal stimulation model. In 20 patients with PD, we mapped motor improvement to active electrode location, relative to the individual, directly MRI-visualized STN. Our analysis included a novel, unconstrained and computational electrical-field model of neuronal activation to estimate the optimal locus of DBS. We mapped the optimal locus to a tightly defined ovoid region 0.49 mm lateral, 0.88 mm posterior, and 2.63 mm dorsal to the anatomical midpoint of the STN. On average, this locus is 11.75 lateral, 1.84 mm posterior, and 1.08 mm ventral to the mid-commissural point. Our novel, atlas-independent method reveals a single, ovoid optimal locus of stimulation in STN DBS for PD. The methodology, here applied to UPDRS and PD, is generalizable to atlas-independent mapping of other motor and non-motor effects of DBS. © 2018 S. Karger AG, Basel.

Screening for early detection of parkinsonism using a self-administered questionnaire: a cross-sectional epidemiologic study.

PubMed

Lundin, Jessica I; Checkoway, Harvey; Criswell, Susan R; Hobson, Angela J; Harris, Rachel C; Swisher, Laura M; Evanoff, Bradley A; Racette, Brad A

2014-12-01

Manganese (Mn) is a common component of welding fume. Exposure to Mn fume has been associated with parkinsonism. A simple and reliable screening tool to evaluate Mn exposed workers for neurotoxic injury would have broad occupational health application. This study investigated 490 occupational welders recruited from a trade union list. Subjects were examined by a movement disorders specialist using the Unified Parkinson Disease Rating Scale motor subsection 3 (UPDRS3). Parkinsonism, intermediate, and normal groups were defined as UPDRS3 score ≥ 15, 6-15, and <6, respectively. Workers completed a health status questionnaire (PDQ39) and a Parkinson disease (PD) Symptoms Questionnaire. Areas under receiver operator curve (AUC) were analyzed based on these scores, adjusted for age, smoking, race, gender, and neurologist, using normal as the reference. The AUC was 0.79 (95% confidence interval [CI]=0.73-0.84) for PDQ39 and 0.78 (95% CI=0.72-0.85) for PD Symptoms Questionnaire score. At 70% sensitivity, the specificity for PDQ39 score and PD Symptoms Questionnaire score for the prediction of parkinsonism was 73.1% and 80.1%, respectively. These results suggest the questionnaires have reasonably good sensitivity and specificity to predict parkinsonism in Mn exposed workers. These questionnaires could be a valuable first step in a tiered screening approach for Mn exposed workers. Copyright © 2013 Elsevier Inc. All rights reserved.

Screening for early detection of parkinsonism using a self-administered questionnaire: a cross-sectional epidemiologic study

PubMed Central

Lundin, Jessica I.; Checkoway, Harvey; Criswell, Susan R.; Hobson, Angela; Harris, Rachel C.; Swisher, Laura M.; Evanoff, Bradley A.; Racette, Brad A.

2013-01-01

Background Manganese (Mn) is a common component of welding fume. Exposure to Mn fume has been associated with parkinsonism. A simple and reliable screening tool to evaluate Mn exposed workers for neurotoxic injury would have broad occupational health application. Methods This study investigated 490 occupational welders recruited from a trade union list. Subjects were examined by a movement disorders specialist using the Unified Parkinson Disease Rating Scale motor subsection 3 (UPDRS3). Parkinsonism, intermediate, and normal groups were defined as UPDRS3 score ≥15, 6–15, and <6, respectively. Workers completed a health status questionnaire (PDQ39) and a Parkinson’s disease (PD) Symptoms Questionnaire. Areas under receiver operator curve (AUC) were analyzed based on these scores, adjusted for age, smoking, race, gender, and neurologist, using normal as the reference. Results The AUC was 0.79 (95% Confidence Interval [CI] = 0.73–0.84) for PDQ39 and 0.78 (95% CI = 0.72–0.85) for PD Symptoms Questionnaire score. At 70% sensitivity, the specificity for PDQ39 score and PD Symptoms Questionnaire score for the prediction of parkinsonism was 73.1% and 80.1%, respectively. Conclusions These results suggest the questionnaires have reasonably good sensitivity and specificity to predict parkinsonism in Mn exposed workers. These questionnaires could be a valuable first step in a tiered screening approach for Mn exposed workers. PMID:24035927

Differentiated effects of deep brain stimulation and medication on somatosensory processing in Parkinson's disease.

PubMed

Sridharan, Kousik Sarathy; Højlund, Andreas; Johnsen, Erik Lisbjerg; Sunde, Niels Aagaard; Johansen, Lars Gottfried; Beniczky, Sándor; Østergaard, Karen

2017-07-01

Deep brain stimulation (DBS) and dopaminergic medication effectively alleviate the motor symptoms in Parkinson's disease (PD) patients, but their effects on the sensory symptoms of PD are still not well understood. To explore early somatosensory processing in PD, we recorded magnetoencephalography (MEG) from thirteen DBS-treated PD patients and ten healthy controls during median nerve stimulation. PD patients were measured during DBS-treated, untreated and dopaminergic-medicated states. We focused on early cortical somatosensory processing as indexed by N20m, induced gamma augmentation (31-45Hz and 55-100Hz) and induced beta suppression (13-30Hz). PD patients' motor symptoms were assessed by UPDRS-III. Using Bayesian statistics, we found positive evidence for differentiated effects of treatments on the induced gamma augmentation (31-45Hz) with highest gamma in the dopaminergic-medicated state and lowest in the DBS-treated and untreated states. In contrast, UPDRS-III scores showed beneficial effects of both DBS and dopaminergic medication on the patients' motor symptoms. Furthermore, treatments did not affect the amplitude of N20m. Our results suggest differentiated effects of DBS and dopaminergic medication on cortical somatosensory processing in PD patients despite consistent ameliorating effects of both treatments on PD motor symptoms. The differentiated effect suggests differences in the effect mechanisms of the two treatments. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Bimanual Force Coordination in Parkinson’s Disease Patients with Bilateral Subthalamic Deep Brain Stimulation

PubMed Central

Gorniak, Stacey L.; McIntyre, Cameron C.; Alberts, Jay L.

2013-01-01

Objective Studies of bimanual actions similar to activities of daily living (ADLs) are currently lacking in evaluating fine motor control in Parkinson’s disease patients implanted with bilateral subthalamic deep brain stimulators. We investigated basic time and force characteristics of a bimanual task that resembles performance of ADLs in a group of bilateral subthalamic deep brain stimulation (DBS) patients. Methods Patients were evaluated in three different DBS parameter conditions off stimulation, on clinically derived stimulation parameters, and on settings derived from a patient-specific computational model. Model-based parameters were computed as a means to minimize spread of current to non-motor regions of the subthalamic nucleus via Cicerone Deep Brain Stimulation software. Patients were evaluated off parkinsonian medications in each stimulation condition. Results The data indicate that DBS parameter state does not affect most aspects of fine motor control in ADL-like tasks; however, features such as increased grip force and grip symmetry varied with the stimulation state. In the absence of DBS parameters, patients exhibited significant grip force asymmetry. Overall UPDRS-III and UPDRS-III scores associated with hand function were lower while patients were experiencing clinically-derived or model-based parameters, as compared to the off-stimulation condition. Conclusion While bilateral subthalamic DBS has been shown to alleviate gross motor dysfunction, our results indicate that DBS may not provide the same magnitude of benefit to fine motor coordination. PMID:24244388

Dual-tasks and walking fast: relationship to extra-pyramidal signs in advanced Alzheimer disease.

PubMed

Camicioli, Richard; Bouchard, Thomas; Licis, Lisa

2006-10-25

Extra-pyramidal signs (EPS) and cadence predicted falls risk in patients with advanced Alzheimer disease (AD). Dual task performance predicts falls with variable success. Dual-task performance and walking fast were examined in advanced AD patients with EPS (EPS+, >3 modified Unified Parkinson's Disease Rating Scale [UPDRS] signs) or without EPS (EPS-, three or less UPDRS signs). Demographics, mental and functional status, behavioral impairment, EPS, and quantitative gait measures (GaitRite) were determined. The effects of an automatic dual-task (simple counting) and of walking fast on spatial and temporal gait characteristics were compared between EPS+ and EPS- subjects using a repeated measures design. Cadence decreased, while stride time, swing time and variability in swing time increased with the dual task. Results were insignificant after adjusting for secondary task performance. With walking fast, speed, cadence and stride length increased while stride time, swing time and double support time decreased. Although EPS+ subjects were slower and had decreased stride length, dual task and walking fast effects did not differ from EPS- subjects. Patient characteristics, the type of secondary task and the specific gait measures examined vary in the literature. In this moderately to severely demented population, EPS did not affect "unconscious" (dual task) or "conscious" (walking fast) gait modulation. Given their high falls risk, and retained ability to modulate walking, EPS+ AD patients may be ideal candidates for interventions aimed at preventing falls.

Remotely Programmed Deep Brain Stimulation of the Bilateral Subthalamic Nucleus for the Treatment of Primary Parkinson Disease: A Randomized Controlled Trial Investigating the Safety and Efficacy of a Novel Deep Brain Stimulation System.

PubMed

Li, Dianyou; Zhang, Chencheng; Gault, Judith; Wang, Wei; Liu, Jianmin; Shao, Ming; Zhao, Yanyan; Zeljic, Kristina; Gao, Guodong; Sun, Bomin

2017-01-01

Deep brain stimulation (DBS) is the most commonly performed surgery for the debilitating symptoms of Parkinson disease (PD). However, DBS systems remain largely unaffordable to patients in developing countries, warranting the development of a safe, economically viable, and functionally comparable alternative. To investigate the efficacy and safety of wirelessly programmed DBS of bilateral subthalamic nucleus (STN) in patients with primary PD. Sixty-four patients with primary PD were randomly divided into test and control groups (1:1), where DBS was initiated at either 1 month or 3 months, respectively, after surgery. Safety and efficacy of the treatment were compared between on- and off-medication states 3 months after surgery. Outcome measures included analysis of Unified Parkinson's Disease Rating Scale (UPDRS) scores, duration of "on" periods, and daily equivalent doses of levodopa. All patients were followed up both 6 and 12 months after surgery. Three months after surgery, significant decrease in the UPDRS motor scores were observed for the test group in the off-medication state (25.08 ± 1.00) versus the control group (4.20 ± 1.99). Bilateral wireless programming STN-DBS is safe and effective for patients with primary PD in whom medical management has failed to restore motor function. © 2017 S. Karger AG, Basel.

Study in Parkinson Disease of Exercise (SPARX): Translating high-intensity exercise from animals to humans

PubMed Central

Moore, Charity G.; Schenkman, Margaret; Kohrt, Wendy M.; Delitto, Anthony; Hall, Deborah A.; Corcos, Daniel

2013-01-01

A burgeoning literature suggests that exercise has a therapeutic benefit in persons with Parkinson disease (PD) and in animal models of PD, especially when animals exercise at high intensity. If exercise is to be prescribed as “first-line” or “add-on” therapy in patients with PD, we must demonstrate its efficacy and dose-response effects through testing phases similar to those used in the testing of pharmacologic agents. The SPARX Trial is a multicenter, randomized, controlled, single-blinded, Phase II study that we designed to test the feasibility of using high-intensity exercise to modify symptoms of PD and to simultaneously test the nonfutility of achieving a prespecified change in patients’ motor scores on the Unified Parkinson Disease Rating Scale (UPDRS). The trial began in May 2102 and is in the process of screening, enrolling, and randomly assigning 126 patients with early-stage PD to 1 of 3 groups: usual care (wait-listed controls), moderate-intensity exercise (4 days/week at 60%–65% maximal heart rate [HRmax]), or high-intensity exercise (4 days/week at 80%–85% HRmax). At 6-month follow-up, the trial is randomly reassigning usual care participants to a moderate-intensity or high-intensity exercise group for the remaining 6 months. The goals of the Phase II trial are to determine if participants can exercise at moderate and high intensities; to determine if either exercise yields benefits consistent with meaningful clinical change (nonfutility); and to document safety and attrition. The advantage of using a non-futility approach allows us to efficiently determine if moderate- or high-intensity exercise warrants further large-scale investigation in PD. PMID:23770108

Novel, high-intensity exercise prescription improves muscle mass, mitochondrial function, and physical capacity in individuals with Parkinson's disease

PubMed Central

Kelly, Neil A.; Ford, Matthew P.; Standaert, David G.; Watts, Ray L.; Bickel, C. Scott; Moellering, Douglas R.; Tuggle, S. Craig; Williams, Jeri Y.; Lieb, Laura; Windham, Samuel T.

2014-01-01

We conducted, in persons with Parkinson's disease (PD), a thorough assessment of neuromotor function and performance in conjunction with phenotypic analyses of skeletal muscle tissue, and further tested the adaptability of PD muscle to high-intensity exercise training. Fifteen participants with PD (Hoehn and Yahr stage 2–3) completed 16 wk of high-intensity exercise training designed to simultaneously challenge strength, power, endurance, balance, and mobility function. Skeletal muscle adaptations (P < 0.05) to exercise training in PD included myofiber hypertrophy (type I: +14%, type II: +36%), shift to less fatigable myofiber type profile, and increased mitochondrial complex activity in both subsarcolemmal and intermyofibrillar fractions (I: +45–56%, IV: +39–54%). These adaptations were accompanied by a host of functional and clinical improvements (P < 0.05): total body strength (+30–56%); leg power (+42%); single leg balance (+34%); sit-to-stand motor unit activation requirement (−30%); 6-min walk (+43 m), Parkinson's Disease Quality of Life Scale (PDQ-39, −7.8pts); Unified Parkinson's Disease Rating Scale (UPDRS) total (−5.7 pts) and motor (−2.7 pts); and fatigue severity (−17%). Additionally, PD subjects in the pretraining state were compared with a group of matched, non-PD controls (CON; did not exercise). A combined assessment of muscle tissue phenotype and neuromuscular function revealed a higher distribution and larger cross-sectional area of type I myofibers and greater type II myofiber size heterogeneity in PD vs. CON (P < 0.05). In conclusion, persons with moderately advanced PD adapt to high-intensity exercise training with favorable changes in skeletal muscle at the cellular and subcellular levels that are associated with improvements in motor function, physical capacity, and fatigue perception. PMID:24408997

Constant Current versus Constant Voltage Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease.

PubMed

Ramirez de Noriega, Fernando; Eitan, Renana; Marmor, Odeya; Lavi, Adi; Linetzky, Eduard; Bergman, Hagai; Israel, Zvi

2015-02-18

Background: Subthalamic nucleus (STN) deep brain stimulation (DBS) is an established therapy for advanced Parkinson's disease (PD). Motor efficacy and safety have been established for constant voltage (CV) devices and more recently for constant current (CC) devices. CC devices adjust output voltage to provide CC stimulation irrespective of impedance fluctuation, while the current applied by CV stimulation depends on the impedance that may change over time. No study has directly compared the clinical effects of these two stimulation modalities. Objective: To compare the safety and clinical impact of CC STN DBS to CV STN DBS in patients with advanced PD 2 years after surgery. Methods: Patients were eligible for inclusion if they had undergone STN DBS surgery for idiopathic PD, had been implanted with a Medtronic Activa PC and if their stimulation program and medication had been stable for at least 1 year. This single-center trial was designed as a double-blind, randomized, prospective study with crossover after 2 weeks. Motor equivalence of the 2 modalities was confirmed utilizing part III of the Unified Parkinson's Disease Rating Scale (UPDRS). PD diaries and multiple subjective and objective evaluations of quality of life, depression, cognition and emotional processing were evaluated on both CV and on CC stimulation. Analysis using the paired t test with Bonferroni correction for multiple comparisons was performed to identify any significant difference between the stimulation modalities. Results: 8 patients were recruited (6 men, 2 women); 1 patient did not complete the study. The average age at surgery was 56.7 years (range 47-63). Disease duration at the time of surgery was 7.5 years (range 3-12). Patients were recruited 23.8 months (range 22.5-24) after surgery. At the postoperative study baseline, this patient group showed an average motor improvement of 69% (range 51-97) as measured by the change in UPDRS part III with stimulation alone. Levodopa equivalent medication was reduced on average by 67% (range 15-88). Patients were poorly compliant with PD diaries, and these did not yield useful information. The minor deterioration in quality-of-life scores (Parkinson's Disease Questionnaire-39, Quality of Life Enjoyment and Satisfaction Questionnaire) with CC stimulation were not statistically significant. Two measures of depression (Hamilton Rating Scale D17, Quick Inventory of Depressive Symptomatology - Self-Report) showed a nonsignificant lower score (less depression) with CC stimulation, but a third (Beck Depression Inventory) showed equivalence. Cognitive testing (Mini Mental State Examination) and emotional processing (Montreal Affective Voices) were equivalent for CC and CV. Conclusion: CC STN DBS is safe. For equivalent motor efficacy, no significant difference could be identified between CC and CV stimulation for nonmotor evaluations in PD patients 2 years after surgery. © 2015 S. Karger AG, Basel.

[Clinical characteristics in Parkinson's disease patients with cognitive impairment and effects of cognitive impairment on sleep].

PubMed

Gong, Yan; Xiong, Kang-ping; Mao, Cheng-jie; Huang, Juan-ying; Hu, Wei-dong; Han, Fei; Chen, Rui; Liu, Chun-feng

2013-09-03

To analyze the clinical characteristics, correlation factors and clinical heterogeneities in Parkinson's disease (PD) patients with cognitive impairment and identify whether cognitive impairment could influence the aspect of sleep. A total of 130 PD outpatients and inpatients of sleep center at our hospital were eligible for participation. According to Montreal cognitive assessment (MOCA), they were divided into cognitive normal group (MOCA ≥ 26) (n = 51) and cognitive impairment group (MOCA < 26) (n = 79). Their clinical characteristics were mainly evaluated by unified Parkinson's disease rating scale (UPDRS) , Hoehn-Yahr (H-Y) stage, Hamilton depression scale (HAMD-24 item) and Epworth sleepiness scale (ESS). And all of them underwent video-polysomnography (PSG). The proportion of cognitive impairment (MOCA < 26) was 60.76%. Compared to those without cognitive impairment, the PD patients with cognitive impairment had significantly higher score of HAMD (10 ± 7 vs 7 ± 4), increased incidence of hallucinations (40.50% vs 19.60%) and REM behavior disorders (RBD) (63.29% vs 39.21%), significantly higher H-Y stage [2.5(2.0-3.0) vs 2.0 (2.0-2.5)] , United Kingdom Parkinson Disease Society (UPDRS) part III (22 ± 10 vs 19 ± 10) and levodopa-equivalent daily dose (LED) (511 ± 302vs 380 ± 272) (all P < 0.05). However, no significant differences existed in the subscores of MOCA between PD patients with different sides of onset and motor subtypes of onset (all P > 0.05). Non-conditional Logistic regression analysis showed that PD duration, score of HAMD and H-Y stage were the major influencing factors of cognition. On PSG, significantly decreased sleep efficiency (57% ± 21% vs 66% ± 17%), higher percentage of non-REM sleep stage 1 (NREMS1) (37% ± 21% vs 27% ± 13%), lower percentage of NREMS2 (40% ± 17% vs 46% ± 13%) and REM sleep (39% ± 28% vs 54% ± 36%) were found for PD patients with cognitive impairment (all P < 0.05). The PD patients with cognitive impairment have more severe disease and partial nonmotor symptoms. And the severity of disease and depression is closely associated with cognitive impairment. Cognitive impairment may also affect sleep to cause decreased sleep efficiency and severe sleep structure disorder.

Real life cost and quality of life associated with continuous intraduodenal levodopa infusion compared with oral treatment in Parkinson patients.

PubMed

Lundqvist, Christofer; Beiske, Antonie Giæver; Reiertsen, Ola; Kristiansen, Ivar Sønbø

2014-12-01

Advanced-stage Parkinson's disease (PD) strongly affects quality of life (QoL). Continuous intraduodenal administration of levodopa (IDL) is efficacious, but entails high costs. This study aims to estimate these costs in routine care. 10 patients with advanced-PD who switched from oral medication to IDL were assessed at baseline, and subsequently at 3, 6, 9 and 12 months follow-up. We used the Unified PD Rating Scale (UPDRS) for function and 15D for Quality of Life (QoL). Costs were assessed using quarterly structured patient questionnaires and hospital registries. Costs per quality adjusted life year (QALY) were estimated for conventional treatment prior to switch and for 1-year treatment with IDL. Probabilistic sensitivity analysis was based on bootstrapping. IDL significantly improved functional scores and was safe to use. One-year conventional oral treatment entailed 0.63 QALY while IDL entailed 0.68 (p > 0.05). The estimated total 1-year treatment cost was NOK419,160 on conventional treatment and NOK890,920 on IDL, representing a cost of NOK9.2 million (€1.18 mill) per additional QALY. The incremental cost per unit UPDRS improvement was NOK25,000 (€3,250). Medication was the dominant cost during IDL (45% of total costs), it represented only 6.4% of the total for conventional treatment. IDL improves function but is not cost effective using recommended thresholds for cost/QALY in Norway.

Partial Body Weight-Supported Treadmill Training in Patients With Parkinson Disease: Impact on Gait and Clinical Manifestation.

PubMed

Ganesan, Mohan; Sathyaprabha, Talakad N; Pal, Pramod Kumar; Gupta, Anupam

2015-09-01

To evaluate the effect of conventional gait training (CGT) and partial weight-supported treadmill training (PWSTT) on gait and clinical manifestation. Prospective experimental research design. Hospital. Patients with idiopathic Parkinson disease (PD) (N=60; mean age, 58.15±8.7y) on stable dosage of dopaminomimetic drugs were randomly assigned into the 3 following groups (20 patients in each group): (1) nonexercising PD group, (2) CGT group, and (3) PWSTT group. The interventions included in the study were CGT and PWSTT. The sessions of the CGT and PWSTT groups were given in patient's self-reported best on status after regular medications. The interventions were given for 30min/d, 4d/wk, for 4 weeks (16 sessions). Clinical severity was measured by the Unified Parkinson Disease Rating Scale (UPDRS) and its subscores. Gait was measured by 2 minutes of treadmill walking and the 10-m walk test. Outcome measures were evaluated in their best on status at baseline and after the second and fourth weeks. Four weeks of CGT and PWSTT gait training showed significant improvements of UPDRS scores, its subscores, and gait performance measures. Moreover, the effects of PWSTT were significantly better than CGT on most measures. PWSTT is a promising intervention tool to improve the clinical and gait outcome measures in patients with PD. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Twice-Daily versus Once-Daily Pramipexole Extended Release Dosage Regimens in Parkinson's Disease.

PubMed

Yun, Ji Young; Kim, Young Eun; Yang, Hui-Jun; Kim, Han-Joon; Jeon, Beomseok

2017-01-01

This open-label study aimed to compare once-daily and twice-daily pramipexole extended release (PER) treatment in Parkinson's disease (PD). PD patients on dopamine agonist therapy, but with unsatisfactory control, were enrolled. Existing agonist doses were switched into equivalent PER doses. Subjects were consecutively enrolled into either once-daily-first or twice-daily-first groups and received the prescribed amount in one or two, respectively, daily doses for 8 weeks. For the second period, subjects switched regimens in a crossover manner. The forty-four patients completed a questionnaire requesting preference during their last visit. We measured the UPDRS-III, Hoehn and Yahr stages (H&Y) in medication-on state, Parkinson's disease sleep scale (PDSS), and Epworth Sleepiness Scale. Eighteen patients preferred a twice-daily regimen, 12 preferred a once-daily regimen, and 14 had no preference. After the trial, 14 subjects wanted to be on a once-daily regimen, 25 chose a twice-daily regimen, and 5 wanted to maintain the prestudy regimen. Main reasons for choosing the twice-daily regimen were decreased off-duration, more tolerable off-symptoms, and psychological stability. The mean UPDRS-III, H&Y, and PDSS were not different. Daytime sleepiness was significantly high in the once-daily regimen, whereas nocturnal hallucinations were more common in the twice-daily. Multiple dosing should be considered if once-daily dosing is unsatisfactory. This study is registered as NCT01515774 at ClinicalTrials.gov.

Cabergoline versus levodopa monotherapy: a decision analysis.

PubMed

Smala, Antje M; Spottke, E Annika; Machat, Olaf; Siebert, Uwe; Meyer, Dieter; Köhne-Volland, Rudolf; Reuther, Martin; DuChane, Janeen; Oertel, Wolfgang H; Berger, Karin B; Dodel, Richard C

2003-08-01

We evaluated the incremental cost-effectiveness of cabergoline compared with levodopa monotherapy in patients with early Parkinson's disease (PD) in the German healthcare system. The study design was based on cost-effectiveness analysis using a Markov model with a 10-year time horizon. Model input data was based on a clinical trial "Early Treatment of PD with Cabergoline" as well as on cost data of a German hospital/office-based PD network. Direct and indirect medical and nonmedical costs were included. Outcomes were costs, disease stage, cumulative complication incidence, and mortality. An annual discount rate of 5% was applied and the societal perspective was chosen. The target population included patients in Hoehn and Yahr Stages I to III. It was found that the occurrence of motor complications was significantly lower in patients on cabergoline monotherapy. For patients aged >/=60 years of age, cabergoline monotherapy was cost effective when considering costs per decreased UPDRS score. Each point decrease in the UPDRS (I-IV) resulted in costs of euro;1,031. Incremental costs per additional motor complication-free patient were euro;104,400 for patients <60 years of age and euro;57,900 for patients >/=60 years of age. In conclusion, this decision-analytic model calculation for PD was based almost entirely on clinical and observed data with a limited number of assumptions. Although costs were higher in patients on cabergoline, the corresponding cost-effectiveness ratio for cabergoline was at least as favourable as the ratios for many commonly accepted therapies. Copyright 20032003 Movement Disorder Society

[Quantitative measurement of axial rigidity, functional status and health-related quality of life in patients with Parkinson's disease].

PubMed

Cano de la Cuerda, Roberto; Vela, Lydia; Miangolarra-Page, Juan Carlos; Macías-Macías, Yolanda; Muñoz-Hellín, Elena

2010-08-16

Rigidity is a cardinal symptom of Parkinson's disease (PD). Clinically, rigidity is usually assessed by passively flexing and extending a patient's limb. Few studies have assessed rigidity in trunk muscles in PD patients. To develop an objective measurement to quantify trunk rigidity in PD patients, and to examine its relationship with disease severity using the Hoehn and Yahr staging score (HY) and the Unified Parkinson's Disease Rating Scale III (UPDRS-III), disease duration, functional status with the Schwab & England activities of daily living scale and health related quality of life (HRQoL) was assessed with the European Quality of Life-5 Dimensions and Parkinson's Disease Questionnaire-39 items (PDQ-39). An isokinetic dynamometer Biodex System 3 was employed to assess trunk rigidity in 36 PD patients. Passive trunk flexion and extension at 3 angular velocities, 30 degrees/s, 45 degrees/s and 60 degrees /s were applied and resistive torques were recorded as trunk flexor and extensors rigidity. Significant correlations between trunk flexors-extensors tone and HY staging score, UPDRS-III, disease duration and functional status at 30 degrees/s, 45 degrees/s and 60 degrees/s were obtained. Trunk rigidity was correlated with the HRQoL assessed with the PDQ-39. Our results suggest that the 30 degrees/s, 45 degrees/s and 60 degrees/s angular velocities of this objective method was valid to assess trunk rigidity and was correlated with disease severity, disease duration, functional status and HRQoL in PD patients.

Comparison of strength training, aerobic training, and additional physical therapy as supplementary treatments for Parkinson’s disease: pilot study

PubMed Central

Carvalho, Alessandro; Barbirato, Dannyel; Araujo, Narahyana; Martins, Jose Vicente; Cavalcanti, Jose Luiz Sá; Santos, Tony Meireles; Coutinho, Evandro S; Laks, Jerson; Deslandes, Andrea C

2015-01-01

Introduction Physical rehabilitation is commonly used in patients with Parkinson’s disease (PD) to improve their health and alleviate the symptoms. Objective We compared the effects of three programs, strength training (ST), aerobic training (AT), and physiotherapy, on motor symptoms, functional capacity, and electroencephalographic (EEG) activity in PD patients. Methods Twenty-two patients were recruited and randomized into three groups: AT (70% of maximum heart rate), ST (80% of one repetition maximum), and physiotherapy (in groups). Subjects participated in their respective interventions twice a week for 12 weeks. The assessments included measures of disease symptoms (Unified Parkinson’s Disease Rating Scale [UPDRS]), functional capacity (Senior Fitness Test), and EEG before and after 12 weeks of intervention. Results The PD motor symptoms (UPDRS-III) in the group of patients who performed ST and AT improved by 27.5% (effect size [ES]=1.25, confidence interval [CI]=−0.11, 2.25) and 35% (ES=1.34, CI=−0.16, 2.58), respectively, in contrast to the physiotherapy group, which showed a 2.9% improvement (ES=0.07, CI=−0.85, 0.99). Furthermore, the functional capacity of all three groups improved after the intervention. The mean frequency of the EEG analysis mainly showed the effect of the interventions on the groups (F=11.50, P=0.0001). Conclusion ST and AT in patients with PD are associated with improved outcomes in disease symptoms and functional capacity. PMID:25609935

Quantitative EEG reflects non-dopaminergic disease severity in Parkinson's disease.

PubMed

Geraedts, Victor J; Marinus, Johan; Gouw, Alida A; Mosch, Arne; Stam, Cornelis J; van Hilten, Jacobus J; Contarino, Maria Fiorella; Tannemaat, Martijn R

2018-05-29

In Parkinson's Disease (PD), measures of non-dopaminergic systems involvement may reflect disease severity and therefore contribute to patient-selection for Deep Brain Stimulation (DBS). There is currently no determinant for non-dopaminergic disease severity. In this exploratory study, we investigated whether quantitative EEG reflects non-dopaminergic disease severity in PD. Sixty-three consecutive PD patients screened for DBS were included (mean age 62.4 ± 7.2 years, 32% females). Relative spectral powers and the Phase-Lag-Index (PLI) reflecting functional connectivity were analysed on routine EEGs. Non-dopaminergic disease severity was quantified using the SENS-PD score and its subdomains; motor-severity was quantified using the MDS-UPDRS III. The SENS-PD composite score correlated with a spectral ratio ((δ + θ)/(α1 + α2 + β) powers) (global spectral ratio Pearson's r = 0.4, 95% Confidence Interval (95%CI) 0.1-0.6), and PLI in the α2 band (10-13 Hz) (r = -0.3, 95%CI -0.5 to -0.1). These correlations seem driven by the subdomains cognition and psychotic symptoms. MDS-UPDRS III was not significantly correlated with EEG parameters. EEG slowing and reduced functional connectivity in the α2 band were associated with non-dopaminergic disease severity in PD. The described EEG parameters may have complementary utility as determinants of non-dopaminergic involvement in PD. Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Impact of Current Antipsychotic Medications on Comparative Mortality and Adverse Events in People With Parkinson Disease Psychosis.

PubMed

Ballard, Clive; Isaacson, Stuart; Mills, Roger; Williams, Hilde; Corbett, Anne; Coate, Bruce; Pahwa, Rajesh; Rascol, Olivier; Burn, David J

2015-10-01

To establish the mortality risk and adverse events associated with the use of atypical antipsychotic medications in people with Parkinson disease psychosis (PDP) in a clinically defined trial cohort. Post hoc analysis of data from a multicenter, open-label extension study of pimavanserin comparing people taking and not taking current antipsychotics. Primary and secondary care medical centers in the United States, Canada, Europe, and India. A total of 459 people with PDP enrolled in the extension study. Participants were between ages 30 and 80 years, and had an established diagnosis of idiopathic Parkinson disease and moderate to severe psychosis. Participants were categorized into 2 groups: those receiving concomitant antipsychotic medications ("concurrent APD") and those who did not take antipsychotic medications at any time during the study ("no APD"). Participants were receiving 40 mg pimavanserin daily in addition to concurrent antipsychotics and Parkinson disease medications. Safety assessments at 2 weeks; 1, 3, 6, 9, and 12 months; and every 6 months thereafter, including evaluation of adverse events (AEs), vital signs, weight, physical examinations, 12-lead electrocardiograms, clinical laboratory tests (serum chemistry, hematology, and urinalysis), and the Unified Parkinson's Disease Rating Scale Parts II and III (UPDRS-II+III, activities of daily living and motor impairment, respectively). Differences between participants taking and not taking current antipsychotics were evaluated using incidence rate ratios (IRRs) with 95% confidence intervals (CIs). There was significant increase in the mortality rate for participants taking concurrent antipsychotics compared with the group not taking antipsychotic medications (IRR 4.20, 95% CI 2.13-7.96). Participants who received a concurrent antipsychotic were also significantly more likely to experience overall a serious AE (IRR 2.95, 95% CI 2.02-4.24), any antipsychotic-related event (IRR 1.66, 95% CI 1.18-2.29), cognition-related events (IRR 2.70, 95% CI 1.19-5.58), infections (IRR 1.97, 95% CI 1.17-3.16), and edema (IRR 2.61, 95% CI 1.09-5.59). The risk of falls, stroke, sedation, orthostatic hypotension, and thromboembolic events was also increased in these individuals but this was not significant. This study highlights a significant risk of mortality, and severe AEs in patients with Parkinson disease receiving atypical antipsychotics. This is similar to or greater than the risks seen in people with Alzheimer disease, although with a less clear-cut risk of stroke and a longer delay to increased mortality. Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

40 CFR 52.2465 - Original identification of plan section.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., 2FSD, and pre-dryer 3FSD from Part IV, Rule EX-4, Section 4.41(i) until December 15, 1981, submitted on...) Appendix K (7) Appendix N (8) Appendix P (9) Appendix R I., II.B., II.D., II.E., II.F., II.G., II.H., II.I...) Amendments to Part I, Subpart 1.01 (Certain Terms Defined) and to Part IV, Section 4.52 (former Section 4.705...

Optimizing care of residents with Parkinsonism in supervised facilities.

PubMed

Makoutonina, Margarita; Iansek, Robert; Simpson, Pam

2010-06-01

People with Parkinsonism (PWP) in residential facilities are usually elderly, cognitively impaired, physically disabled with poor quality of life and a high mortality rate. This paper aims to determine if the care of PWP in residential facilities could be improved by addressing staff knowledge on Parkinson related issues. A curriculum based on the Victorian Comprehensive Parkinson Program (VCPP) was developed and delivered to 118 staff members in 9 facilities across Melbourne. Measures of staff knowledge were undertaken at baseline, 1, 3 and 12 months. Data from a total of 49 residents were used in the analysis. Measures were taken at baseline, 1, 3 and 12 months included dementia screen (MMSE), geriatric depression scale (GDS), quality of life (PDQ39), fatigue (PDFS16), monthly falls diary, Unified Parkinson Disease Rating Scale (I,II,III) Hoehn & Yahr scale (H&Y) and resident/family questionnaire (RFQ) which focused on quality of care provision. It was found that the staff knowledge assessment scores (max = 37) significantly improved post education (P < 0.01) from baseline mean (11.1) and were maintained to 12 months mean (29.0). The residents group improved significantly for all measures at 1 month and these improvements were maintained up to 12 months (except for UPDRS III). This study demonstrated how a simple intervention, resulting in improved staff knowledge, produced a significant and clinically meaningful improvement in the care of PWP.

Effects of parkinsonism on health status in welding exposed workers.

PubMed

Harris, Rachel C; Lundin, Jessica I; Criswell, Susan R; Hobson, Angela; Swisher, Laura M; Evanoff, Bradley A; Checkoway, Harvey; Racette, Brad A

2011-11-01

Previous studies suggest that welders frequently display parkinsonian signs, such as bradykinesia and tremor. Demonstrating that these parkinsonian findings are associated with reductions in quality of life (QoL) or health status could have important repercussions for worker safety and performance. Subjects included 394 active workers exposed to welding fumes and evaluated for parkinsonism by movement disorders experts in a worksite-based epidemiology study. Subjects were diagnosed with parkinsonism if the Unified Parkinson Disease Rating Scale motor subsection part 3 (UPDRS3) score was ≥15. All subjects completed a Parkinson's disease (PD) symptom questionnaire and the PDQ39, a widely used QoL and health status measure for PD. Total PDQ39 score and all subscores were greater in welders with parkinsonism than welders without parkinsonism, with the most significant differences observed for mobility, emotional well-being, and activities of daily living (ADL's). The PDQ39 scores for welding exposed workers with parkinsonism were similar to scores seen in a group of early PD patients. Parkinsonism in active, welding exposed workers is associated with reductions in health status and QoL affecting a broad range of categories and within the range seen in early PD. Copyright © 2011 Elsevier Ltd. All rights reserved.

Effects of Parkinsonism on Health Status in Welding Exposed Workers

PubMed Central

Harris, Rachel C.; Lundin, Jessica I.; Criswell, Susan R.; Hobson, Angela; Swisher, Laura M.; Evanoff, Bradley A.; Checkoway, Harvey; Racette, Brad A.

2011-01-01

Background Previous studies suggest that welders frequently display parkinsonian signs, such as bradykinesia and tremor. Demonstrating that these parkinsonian findings are associated with reductions in quality of life (QoL) or health status could have important repercussions for worker safety and performance. Methods Subjects included 394 active workers exposed to welding fumes and evaluated for parkinsonism by movement disorders experts in a worksite-based epidemiology study. Subjects were diagnosed with parkinsonism if the Unified Parkinson Disease Rating Scale motor subsection part 3 (UPDRS3) score was >15. All subjects completed a Parkinson’s disease (PD) symptom questionnaire and the PDQ39, a widely used QoL and health status measure for PD. Results Total PDQ39 score and all subscores were greater in welders with parkinsonism than welders without parkinsonism, with the most significant differences observed for mobility, emotional well-being, and activities of daily living (ADL’s). The PDQ39 scores for welding exposed workers with parkinsonism were similar to scores seen in a group of early PD patients. Conclusion Parkinsonism in active, welding exposed workers is associated with reductions in health status and QoL affecting a broad range of categories and within the range seen in early PD. PMID:21724446

Effects of medication and subthalamic nucleus deep brain stimulation on tongue movements in speakers with Parkinson's disease using electropalatography: a pilot study.

PubMed

Hartinger, Mariam; Tripoliti, Elina; Hardcastle, William J; Limousin, Patricia

2011-03-01

Parkinson's disease (PD) affects speech in the majority of patients. Subthalamic nucleus deep brain stimulation (STN-DBS) is particularly effective in reducing tremor and rigidity. However, its effect on speech is variable. The aim of this pilot study was to quantify the effects of bilateral STN-DBS and medication on articulation, using electropalatography (EPG). Two patients, PT1 and PT2, were studied under four conditions: on and off medication and ON and OFF stimulation. The EPG protocol consisted of a number of target words with alveolar and velar stops, repeated 10 times in random order. The motor part III of the Unified Parkinson Disease Rating Scale (UPDRS) indicated significantly improved motor scores in the ON stimulation condition in both patients. However, PT1's articulation patterns deteriorated with stimulation whereas PT2 showed improving articulatory accuracy in the same condition. The results revealed different effects of stimulation and medication on articulation particularly with regard to timing. The study quantified less articulatory undershoot for velar stops in comparison to alveolars. Furthermore, the findings provided preliminary evidence that stimulation with medication has a more detrimental effect on articulation than stimulation without medication.

19 CFR Annex II to Part 351 - Deadlines for Parties in Countervailing Administrative Reviews

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 3 2010-04-01 2010-04-01 false Deadlines for Parties in Countervailing Administrative Reviews II Annex II to Part 351 Customs Duties INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE ANTIDUMPING AND COUNTERVAILING DUTIES Pt. 351, Annex II Annex II to Part 351—Deadlines for Parties...

19 CFR Annex II to Part 351 - Deadlines for Parties in Countervailing Administrative Reviews

Code of Federal Regulations, 2011 CFR

2011-04-01

... 19 Customs Duties 3 2011-04-01 2011-04-01 false Deadlines for Parties in Countervailing Administrative Reviews II Annex II to Part 351 Customs Duties INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE ANTIDUMPING AND COUNTERVAILING DUTIES Pt. 351, Annex II Annex II to Part 351—Deadlines for Parties...

19 CFR Annex II to Part 351 - Deadlines for Parties in Countervailing Administrative Reviews

Code of Federal Regulations, 2014 CFR

2014-04-01

... 19 Customs Duties 3 2014-04-01 2014-04-01 false Deadlines for Parties in Countervailing Administrative Reviews II Annex II to Part 351 Customs Duties INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE ANTIDUMPING AND COUNTERVAILING DUTIES Pt. 351, Annex II Annex II to Part 351—Deadlines for Parties...

19 CFR Annex II to Part 351 - Deadlines for Parties in Countervailing Administrative Reviews

Code of Federal Regulations, 2013 CFR

2013-04-01

... 19 Customs Duties 3 2013-04-01 2013-04-01 false Deadlines for Parties in Countervailing Administrative Reviews II Annex II to Part 351 Customs Duties INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE ANTIDUMPING AND COUNTERVAILING DUTIES Pt. 351, Annex II Annex II to Part 351—Deadlines for Parties...

19 CFR Annex II to Part 351 - Deadlines for Parties in Countervailing Administrative Reviews

Code of Federal Regulations, 2012 CFR

2012-04-01

... 19 Customs Duties 3 2012-04-01 2012-04-01 false Deadlines for Parties in Countervailing Administrative Reviews II Annex II to Part 351 Customs Duties INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE ANTIDUMPING AND COUNTERVAILING DUTIES Pt. 351, Annex II Annex II to Part 351—Deadlines for Parties...

10 CFR Appendix II to Part 504 - Fuel Price Computation

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 4 2012-01-01 2012-01-01 false Fuel Price Computation II Appendix II to Part 504 Energy DEPARTMENT OF ENERGY (CONTINUED) ALTERNATE FUELS EXISTING POWERPLANTS Pt. 504, App. II Appendix II to Part 504—Fuel Price Computation (a) Introduction. This appendix provides the equations and parameters...

40 CFR Appendix II to Part 1048 - Large Spark-ignition (SI) Composite Transient Cycle

Code of Federal Regulations, 2010 CFR

2010-07-01

... Transient Cycle II Appendix II to Part 1048 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY.... 1048, App. II Appendix II to Part 1048—Large Spark-ignition (SI) Composite Transient Cycle The following table shows the transient duty-cycle for engines that are not constant-speed engines, as described...

40 CFR Appendix II to Part 261 - [Reserved

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 25 2010-07-01 2010-07-01 false [Reserved] II Appendix II to Part 261 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) IDENTIFICATION AND LISTING OF HAZARDOUS WASTE Appendix II to Part 261 [Reserved] ...

40 CFR Appendix II to Part 600 - Sample Fuel Economy Calculations

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Sample Fuel Economy Calculations II Appendix II to Part 600 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) ENERGY POLICY FUEL ECONOMY AND CARBON-RELATED EXHAUST EMISSIONS OF MOTOR VEHICLES Pt. 600, App. II Appendix II to Part 600—Sample Fuel Economy Calculations (...

10 CFR Appendix II to Part 504 - Fuel Price Computation

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 4 2013-01-01 2013-01-01 false Fuel Price Computation II Appendix II to Part 504 Energy DEPARTMENT OF ENERGY (CONTINUED) ALTERNATE FUELS EXISTING POWERPLANTS Pt. 504, App. II Appendix II to Part... effects of future real price increases for each fuel. The delivered price of an alternate fuel used to...

10 CFR Appendix II to Part 504 - Fuel Price Computation

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 4 2014-01-01 2014-01-01 false Fuel Price Computation II Appendix II to Part 504 Energy DEPARTMENT OF ENERGY (CONTINUED) ALTERNATE FUELS EXISTING POWERPLANTS Pt. 504, App. II Appendix II to Part... (APXi). If an alternate fuel other than coal is proposed the source or the derivation of the index must...

10 CFR Appendix II to Part 504 - Fuel Price Computation

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Fuel Price Computation II Appendix II to Part 504 Energy DEPARTMENT OF ENERGY (CONTINUED) ALTERNATE FUELS EXISTING POWERPLANTS Pt. 504, App. II Appendix II to Part... effects of future real price increases for each fuel. The delivered price of an alternate fuel used to...

Combined Vision and Wearable Sensors-based System for Movement Analysis in Rehabilitation.

PubMed

Spasojević, Sofija; Ilić, Tihomir V; Milanović, Slađan; Potkonjak, Veljko; Rodić, Aleksandar; Santos-Victor, José

2017-03-23

Traditional rehabilitation sessions are often a slow, tedious, disempowering and non-motivational process, supported by clinical assessment tools, i.e. evaluation scales that are prone to subjective rating and imprecise interpretation of patient's performance. Poor patient motivation and insufficient accuracy are thus critical factors that can be improved by new sensing / processing technologies. We aim to develop a portable and affordable system, suitable for home rehabilitation, which combines vision-based and wearable sensors. We introduce a novel approach for examining and characterizing the rehabilitation movements, using quantitative descriptors. We propose new Movement Performance Indicators (MPIs) that are extracted directly from sensor data and quantify the symmetry, velocity, and acceleration of the movement of different body/hand parts, and that can potentially be used by therapists for diagnosis and progress assessment. First, a set of rehabilitation exercises is defined, with the supervision of neurologists and therapists for the specific case of Parkinson's disease. It comprises full-body movements measured with a Kinect device and fine hand movements, acquired with a data glove. Then, the sensor data is used to compute 25 Movement Performance Indicators, to assist the diagnosis and progress monitoring (assessing the disease stage) in Parkinson's disease. A kinematic hand model is developed for data verification and as an additional resource for extracting supplementary movement information. Our results show that the proposed Movement Performance Indicators are relevant for the Parkinson's disease assessment. This is further confirmed by correlation of the proposed indicators with clinical tapping test and UPDRS clinical scale. Classification results showed the potential of these indicators to discriminate between the patients and controls, as well as between the stages that characterize the evolution of the disease. The proposed sensor system, along with the developed approach for rehabilitation movement analysis have a significant potential to support and advance traditional rehabilitation therapy. The main impact of our work is two-fold: (i) the proposition of an approach for supporting the therapists during the diagnosis and monitoring evaluations by reducing subjectivity and imprecision, and (ii) offering the possibility of the system to be used at home for rehabilitation exercises in between sessions with doctors and therapists.

Action Observation Plus Sonification. A Novel Therapeutic Protocol for Parkinson’s Patient with Freezing of Gait

PubMed Central

Mezzarobba, Susanna; Grassi, Michele; Pellegrini, Lorella; Catalan, Mauro; Kruger, Bjorn; Furlanis, Giovanni; Manganotti, Paolo; Bernardis, Paolo

2018-01-01

Freezing of gait (FoG) is a disabling symptom associated with falls, with little or no responsiveness to pharmacological treatment. Current protocols used for rehabilitation are based on the use of external sensory cues. However, cued strategies might generate an important dependence on the environment. Teaching motor strategies without cues [i.e., action observation (AO) plus Sonification] could represent an alternative/innovative approach to rehabilitation that matters most on appropriate allocation of attention and lightening cognitive load. We aimed to test the effects of a novel experimental protocol to treat patients with Parkinson’s disease (PD) and FoG, using functional, and clinical scales. The experimental protocol was based on AO plus Sonification. 12 patients were treated with 8 motor gestures. They watched eight videos showing an actor performing the same eight gestures, and then tried to repeat each gesture. Each video was composed by images and sounds of the gestures. By means of the Sonification technique, the sounds of gestures were obtained by transforming kinematic data (velocity) recorded during gesture execution, into pitch variations. The same 8 motor gestures were also used in a second group of 10 patients; which were treated with a standard protocol based on a common sensory stimulation method. All patients were tested with functional and clinical scales before, after, at 1 month, and 3 months after the treatment. Data showed that the experimental protocol have positive effects on functional and clinical tests. In comparison with the baseline evaluations, significant performance improvements were seen in the NFOG questionnaire, and the UPDRS (parts II and III). Importantly, all these improvements were consistently observed at the end, 1 month, and 3 months after treatment. No improvement effects were found in the group of patients treated with the standard protocol. These data suggest that a multisensory approach based on AO plus Sonification, with the two stimuli semantically related, could help PD patients with FoG to relearn gait movements, to reduce freezing episodes, and that these effects could be prolonged over time. PMID:29354092

10 CFR Appendix II to Part 960 - NRC and EPA Requirements for Preclosure Repository Performance

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 4 2012-01-01 2012-01-01 false NRC and EPA Requirements for Preclosure Repository Performance II Appendix II to Part 960 Energy DEPARTMENT OF ENERGY GENERAL GUIDELINES FOR THE PRELIMINARY SCREENING OF POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Pt. 960, App. II Appendix II to Part 960—NRC and...

10 CFR Appendix II to Part 960 - NRC and EPA Requirements for Preclosure Repository Performance

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false NRC and EPA Requirements for Preclosure Repository Performance II Appendix II to Part 960 Energy DEPARTMENT OF ENERGY GENERAL GUIDELINES FOR THE PRELIMINARY SCREENING OF POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Pt. 960, App. II Appendix II to Part 960—NRC and...

10 CFR Appendix II to Part 960 - NRC and EPA Requirements for Preclosure Repository Performance

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 4 2013-01-01 2013-01-01 false NRC and EPA Requirements for Preclosure Repository Performance II Appendix II to Part 960 Energy DEPARTMENT OF ENERGY GENERAL GUIDELINES FOR THE PRELIMINARY SCREENING OF POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Pt. 960, App. II Appendix II to Part 960—NRC and...

10 CFR Appendix II to Part 960 - NRC and EPA Requirements for Preclosure Repository Performance

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 4 2014-01-01 2014-01-01 false NRC and EPA Requirements for Preclosure Repository Performance II Appendix II to Part 960 Energy DEPARTMENT OF ENERGY GENERAL GUIDELINES FOR THE PRELIMINARY SCREENING OF POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Pt. 960, App. II Appendix II to Part 960—NRC and...

Intermittent theta-burst transcranial magnetic stimulation for treatment of Parkinson disease.

PubMed

Benninger, D H; Berman, B D; Houdayer, E; Pal, N; Luckenbaugh, D A; Schneider, L; Miranda, S; Hallett, M

2011-02-15

To investigate the safety and efficacy of intermittent theta-burst stimulation (iTBS) in the treatment of motor symptoms in Parkinson disease (PD). Progression of PD is characterized by the emergence of motor deficits, which eventually respond less to dopaminergic therapy and pose a therapeutic challenge. Repetitive transcranial magnetic stimulation (rTMS) has shown promising results in improving gait, a major cause of disability, and may provide a therapeutic alternative. iTBS is a novel type of rTMS that may be more efficacious than conventional rTMS. In this randomized, double-blind, sham-controlled study, we investigated safety and efficacy of iTBS of the motor and dorsolateral prefrontal cortices in 8 sessions over 2 weeks (evidence Class I). Assessment of safety and clinical efficacy over a 1-month period included timed tests of gait and bradykinesia, Unified Parkinson's Disease Rating Scale (UPDRS), and additional clinical, neuropsychological, and neurophysiologic measures. We investigated 26 patients with mild to moderate PD: 13 received iTBS and 13 sham stimulation. We found beneficial effects of iTBS on mood, but no improvement of gait, bradykinesia, UPDRS, and other measures. EEG/EMG monitoring recorded no pathologic increase of cortical excitability or epileptic activity. Few reported discomfort or pain and one experienced tinnitus during real stimulation. iTBS of the motor and prefrontal cortices appears safe and improves mood, but failed to improve motor performance and functional status in PD. This study provides Class I evidence that iTBS was not effective for gait, upper extremity bradykinesia, or other motor symptoms in PD.

Backward compared to forward over ground gait retraining have additional benefits for gait in individuals with mild to moderate Parkinson's disease: A randomized controlled trial.

PubMed

Grobbelaar, Roné; Venter, Ranel; Welman, Karen Estelle

2017-10-01

Over ground gait retraining in the reverse direction has shown to be beneficial for neurological rehabilitation, but has not yet been investigated in Parkinson's disease (PD). Backwards walking (BW) might be a useful training alternative to improve PD gait and possibly reduce fall risk during complex multi-directional daily activities. The primary aim was to compare the effect of an eight-week forward (FWG) and backwards (BWG) gait retraining program on gait parameters in PD individuals. Twenty-nine participants (aged 71.0±8.8years; UPDRS-III 38.1±12.3; H&Y 2.7±0.5) were randomly assigned to either the control (FWG; n=14) or experimental group (BWG; n=15). Baseline measures included disease severity (UPDRS III), global cognition (MoCA) and depression (PHQ-9). Outcome measures were selected gait variables on the 10m-instrumented-walk-test (i10mWT) assessed before and after the interventions. Both groups improved usual gait speed (FWG: p=0.03, d=0.35; BWG: p<0.01, d=0.35) and height-normalized gait speed (FWG: p=0.04, d=0.35; BWG: p<0.01, d=0.57). Additionally, the BWG demonstrated improved cadence (p<0.01, d=0.67) and stride length (SL; p=0.02, d=0.39). Both interventions were effective to improved gait speed sufficiently to independently navigate in the community. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of Using the Nintendo Wii Fit Plus Platform in the Sensorimotor Training of Gait Disorders in Parkinson’s Disease

PubMed Central

Gonçalves, Giovanna Barros; Leite, Marco Antônio A.; Orsini, Marco; Pereira, João Santos

2014-01-01

The use of the Nintendo Wii has been considered a good alternative in the motor rehabilitation of individuals with Parkinson’s disease (PD), requiring simultaneous interaction to develop strategies for physical, visual, auditory, cognitive, psychological and social activities in the performing of virtual activities, resulting in improvement in functional performance and gait. The aim of this study was to analyze the effect of virtual sensorimotor activity on gait disorders in people with PD. Fifteen subjects with a clinical diagnosis of PD were submitted to the Unified Parkinson’s Disease Rating Scale (UPDRS III), Schwab and England Activities of Daily Living Scale (SE), Functional Independence Measure (FIM), and biomechanical gait analysis using digital images taken with a video camera before and after the treatment program. The activities with the Nintendo Wii virtual platform were standardized into three categories: aerobics, balance and Wii plus exercises. Participants carried out separate virtual exercises for 40 min, twice a week, for a total of 14 sessions. The program improved sensorimotor performance in PD gait, with an increase in stride length and gait speed, in addition to a reduction in motor impairment, especially in items of rigidity and flexibility of the lower limbs evaluated by UPDRS III, and greater functional independence, as evidenced in the SE and FIM scales. Improvements in items related to locomotion and stair climbing were also observed. The training was effective in motor recovery in chronic neurodegenerative diseases, showing improvement in motor performance and functional independence in individuals with PD. PMID:24744845

Effects of using the nintendo wii fit plus platform in the sensorimotor training of gait disorders in Parkinson's disease.

PubMed

Gonçalves, Giovanna Barros; Leite, Marco Antônio A; Orsini, Marco; Pereira, João Santos

2014-01-17

The use of the Nintendo Wii has been considered a good alternative in the motor rehabilitation of individuals with Parkinson's disease (PD), requiring simultaneous interaction to develop strategies for physical, visual, auditory, cognitive, psychological and social activities in the performing of virtual activities, resulting in improvement in functional performance and gait. The aim of this study was to analyze the effect of virtual sensorimotor activity on gait disorders in people with PD. Fifteen subjects with a clinical diagnosis of PD were submitted to the Unified Parkinson's Disease Rating Scale (UPDRS III), Schwab and England Activities of Daily Living Scale (SE), Functional Independence Measure (FIM), and biomechanical gait analysis using digital images taken with a video camera before and after the treatment program. The activities with the Nintendo Wii virtual platform were standardized into three categories: aerobics, balance and Wii plus exercises. Participants carried out separate virtual exercises for 40 min, twice a week, for a total of 14 sessions. The program improved sensorimotor performance in PD gait, with an increase in stride length and gait speed, in addition to a reduction in motor impairment, especially in items of rigidity and flexibility of the lower limbs evaluated by UPDRS III, and greater functional independence, as evidenced in the SE and FIM scales. Improvements in items related to locomotion and stair climbing were also observed. The training was effective in motor recovery in chronic neurodegenerative diseases, showing improvement in motor performance and functional independence in individuals with PD.

Turo (qi dance) Program for Parkinson's Disease Patients: Randomized, Assessor Blind, Waiting-List Control, Partial Crossover Study.

PubMed

Lee, Hwa-Jin; Kim, Song-Yi; Chae, Younbyoung; Kim, Mi-Young; Yin, Changshik; Jung, Woo-Sang; Cho, Ki-Ho; Kim, Seung-Nam; Park, Hi-Joon; Lee, Hyejung

2018-03-01

Qigong, Tai-chi and dancing have all been proven effective for Parkinson's disease (PD); however, no study has yet assessed the efficacy of Turo, a hybrid qigong dancing program developed to relieve symptoms in PD patients. To determine whether Turo may provide benefit in addressing the symptoms of PD patients. Randomized, assessor blind, waiting-list control, partial crossover study. Kyung Hee University Korean Medicine Hospital, Seoul, Republic of Korea. A total of 32 PD patients (mean age 65.7 ± 6.8). Participants were assigned to the Turo group or the waiting-list control group. The Turo group participated in an 8-week Turo training program (60-minute sessions twice a week). The waiting-list control group received no additional treatment during the same period; then underwent the same 8-week Turo training. The primary outcome was a score on the Unified Parkinson's Disease Rating Scale (UPDRS), and the secondary outcomes included the perceived health status assessed using the Parkinson's disease Quality of Life questionnaire (PDQL), balance function as assessed by the Berg Balance Scale (BBS) and the results of the Beck Depression Inventory (BDI). The Turo group showed statistically significant improvements in the UPDRS (P < 0.01) and PDQL (P < 0.05) as compared to the control group. The changes in BBS scores displayed a tendency toward improvement, but was not statistically significant (P = 0.051). These findings suggest that Turo PD training might improve the symptoms of PD patients. Copyright © 2018. Published by Elsevier Inc.

Connectivity Predicts Deep Brain Stimulation Outcome in Parkinson Disease

PubMed Central

Horn, Andreas; Reich, Martin; Vorwerk, Johannes; Li, Ningfei; Wenzel, Gregor; Fang, Qianqian; Schmitz-Hübsch, Tanja; Nickl, Robert; Kupsch, Andreas; Volkmann, Jens; Kühn, Andrea A.; Fox, Michael D.

2018-01-01

Objective The benefit of deep brain stimulation (DBS) for Parkinson disease (PD) may depend on connectivity between the stimulation site and other brain regions, but which regions and whether connectivity can predict outcome in patients remain unknown. Here, we identify the structural and functional connectivity profile of effective DBS to the subthalamic nucleus (STN) and test its ability to predict outcome in an independent cohort. Methods A training dataset of 51 PD patients with STN DBS was combined with publicly available human connectome data (diffusion tractography and resting state functional connectivity) to identify connections reliably associated with clinical improvement (motor score of the Unified Parkinson Disease Rating Scale [UPDRS]). This connectivity profile was then used to predict outcome in an independent cohort of 44 patients from a different center. Results In the training dataset, connectivity between the DBS electrode and a distributed network of brain regions correlated with clinical response including structural connectivity to supplementary motor area and functional anticorrelation to primary motor cortex (p<0.001). This same connectivity profile predicted response in an independent patient cohort (p<0.01). Structural and functional connectivity were independent predictors of clinical improvement (p<0.001) and estimated response in individual patients with an average error of 15% UPDRS improvement. Results were similar using connectome data from normal subjects or a connectome age, sex, and disease matched to our DBS patients. Interpretation Effective STN DBS for PD is associated with a specific connectivity profile that can predict clinical outcome across independent cohorts. This prediction does not require specialized imaging in PD patients themselves. PMID:28586141

Levodopa-Induced Changes in Electromyographic Patterns in Patients with Advanced Parkinson’s Disease

PubMed Central

Ruonala, Verneri; Pekkonen, Eero; Airaksinen, Olavi; Kankaanpää, Markku; Karjalainen, Pasi A; Rissanen, Saara M

2018-01-01

Levodopa medication is the most efficient treatment for motor symptoms of Parkinson’s disease (PD). Levodopa significantly alleviates rigidity, rest tremor, and bradykinesia in PD. The severity of motor symptoms can be graded with UPDRS-III scale. Levodopa challenge test is routinely used to assess patients’ eligibility to deep-brain stimulation (DBS) in PD. Feasible and objective measurements to assess motor symptoms of PD during levodopa challenge test would be helpful in unifying the treatment. Twelve patients with advanced PD who were candidates for DBS treatment were recruited to the study. Measurements were done in four phases before and after levodopa challenge test. Rest tremor and rigidity were evaluated using UPDRS-III score. Electromyographic (EMG) signals from biceps brachii and kinematic signals from forearm were recorded with wireless measurement setup. The patients performed two different tasks: arm isometric tension and arm passive flexion–extension. The electromyographic and the kinematic signals were analyzed with parametric, principal component, and spectrum-based approaches. The principal component approach for isometric tension EMG signals showed significant decline in characteristics related to PD during levodopa challenge test. The spectral approach on passive flexion–extension EMG signals showed a significant decrease on involuntary muscle activity during the levodopa challenge test. Both effects were stronger during the levodopa challenge test compared to that of patients’ personal medication. There were no significant changes in the parametric approach for EMG and kinematic signals during the measurement. The results show that a wireless and wearable measurement and analysis can be used to study the effect of levodopa medication in advanced Parkinson’s disease. PMID:29459845

Exenatide and the treatment of patients with Parkinson’s disease

PubMed Central

Aviles-Olmos, Iciar; Dickson, John; Kefalopoulou, Zinovia; Djamshidian, Atbin; Ell, Peter; Soderlund, Therese; Whitton, Peter; Wyse, Richard; Isaacs, Tom; Lees, Andrew; Limousin, Patricia; Foltynie, Thomas

2013-01-01

Background. There is increasing interest in methods to more rapidly and cost-efficiently investigate drugs that are approved for clinical use in the treatment of another condition. Exenatide is a type 2 diabetes treatment that has been shown to have neuroprotective/neurorestorative properties in preclinical models of neurodegeneration. Methods. As a proof of concept, using a single-blind trial design, we evaluated the progress of 45 patients with moderate Parkinson’s disease (PD), randomly assigned to receive subcutaneous exenatide injection for 12 months or to act as controls. Their PD was compared after overnight withdrawal of conventional PD medication using blinded video assessment of the Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), together with several nonmotor tests, at baseline, 6 months, and 12 months and after a further 2-month washout period (14 months). Results. Exenatide was well tolerated, although weight loss was common and l-dopa dose failures occurred in a single patient. Single-blinded rating of the exenatide group suggested clinically relevant improvements in PD across motor and cognitive measures compared with the control group. Exenatide-treated patients had a mean improvement at 12 months on the MDS-UPDRS of 2.7 points, compared with mean decline of 2.2 points in control patients (P = 0.037). Conclusion. These results demonstrate a potential cost-efficient approach through which preliminary clinical data of possible biological effects are obtainable, prior to undertaking the major investment required for double-blind trials of a potential disease-modifying drug in PD. Trial registration. Clinicaltrials.gov NCT01174810. Funding. Cure Parkinson’s Trust. PMID:23728174

40 CFR Appendixes I-Ii to Part 268 - [Reserved

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 26 2010-07-01 2010-07-01 false [Reserved] I Appendixes I-II to Part 268 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) LAND DISPOSAL RESTRICTIONS Appendixes I-II to Part 268 [Reserved] ...

40 CFR Appendixes I-Ii to Part 268 - [Reserved

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 27 2011-07-01 2011-07-01 false [Reserved] I Appendixes I-II to Part 268 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) LAND DISPOSAL RESTRICTIONS Appendixes I-II to Part 268 [Reserved] ...

40 CFR Appendixes I-Ii to Part 268 - [Reserved

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 27 2014-07-01 2014-07-01 false [Reserved] I Appendixes I-II to Part 268 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) LAND DISPOSAL RESTRICTIONS Appendixes I-II to Part 268 [Reserved] ...

40 CFR Appendixes I-Ii to Part 268 - [Reserved

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 28 2012-07-01 2012-07-01 false [Reserved] I Appendixes I-II to Part 268 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) LAND DISPOSAL RESTRICTIONS Appendixes I-II to Part 268 [Reserved] ...

40 CFR Appendixes I-Ii to Part 268 - [Reserved

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 28 2013-07-01 2013-07-01 false [Reserved] I Appendixes I-II to Part 268 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) LAND DISPOSAL RESTRICTIONS Appendixes I-II to Part 268 [Reserved] ...

An Analysis of a Finite Element Method for Convection-Diffusion Problems. Part II. A Posteriori Error Estimates and Adaptivity.

DTIC Science & Technology

1983-03-01

AN ANALYSIS OF A FINITE ELEMENT METHOD FOR CONVECTION- DIFFUSION PROBLEMS PART II: A POSTERIORI ERROR ESTIMATES AND ADAPTIVITY by W. G. Szymczak Y 6a...PERIOD COVERED AN ANALYSIS OF A FINITE ELEMENT METHOD FOR final life of the contract CONVECTION- DIFFUSION PROBLEM S. Part II: A POSTERIORI ERROR ...Element Method for Convection- Diffusion Problems. Part II: A Posteriori Error Estimates and Adaptivity W. G. Szvmczak and I. Babu~ka# Laboratory for

Deep Brain Stimulation in Early Parkinson’s Disease: Enrollment Experience from a Pilot Trial

PubMed Central

Charles, PD; Dolhun, RM; Gill, CE; Davis, TL; Bliton, MJ; Tramontana, MG; Salomon, RM; Wang; Hedera, P; Phibbs, FT; Neimat, JS; Konrad, PE

2011-01-01

Background Deep brain stimulation (DBS) of the subthalamic nucleus is an accepted therapy for advanced Parkinson’s disease (PD). In animal models, pharmacologic ablation and stimulation of the subthalamic nucleus have resulted in clinical improvement and, in some cases, improved survival of dopaminergic neurons. DBS has not been studied in the early stages of PD, but early application should be explored to evaluate safety, efficacy, and the potential to alter disease progression. Methods We are conducting a prospective, randomized, single-blind clinical trial of optimal drug therapy (ODT) compared to medication plus DBS (ODT + DBS) in subjects with Hoehn & Yahr Stage II idiopathic PD who are without motor fluctuations or dementia. We report here subject screening, enrollment, baseline characteristics, and adverse events. Results 30 subjects (average age 60 ± 6.9 years, average duration of medicine 2.1 ± 1.3 years, average UPDRS-III scores 14.9 on medication and 27.0 off medication) are enrolled in the ongoing study. Twelve of 15 subjects randomized to DBS experienced perioperative adverse events, the majority of which were related to the procedure or device and resolved without sequelae. Frequently reported adverse events included wound healing problems, headache, edema, and confusion. Conclusion This report demonstrates that subjects with early stage PD can be successfully recruited, consented and retained in a long term clinical trial of DBS. Our ongoing pilot investigation will provide important preliminary safety and tolerability data concerning the application of DBS in early stage PD. PMID:22104012

A Survey of Optometry Graduates to Determine Practice Patterns: Part II: Licensure and Practice Establishment Experiences.

ERIC Educational Resources Information Center

Bleimann, Robert L.; Smith, Lee W.

1985-01-01

A summary of Part II of a two-volume study of optometry graduates conducted by the Association of Schools and Colleges of Optometry is presented. Part II includes the analysis of the graduates' licensure and practice establishment experiences. (MLW)

Brain SPECT can differentiate between essential tremor and early-stage tremor-dominant Parkinson's disease.

PubMed

Song, In-Uk; Park, Jeong-Wook; Chung, Sung-Woo; Chung, Yong-An

2014-09-01

There are no confirmatory or diagnostic tests or tools to differentiate between essential tremor (ET) and tremor in idiopathic Parkinson's disease (PD). Although a number of imaging studies have indicated that there are differences between ET and PD, the functional imaging study findings are controversial. Therefore, we analyzed regional cerebral blood flow (CBF) by perfusion brain single-photon emission computed tomography (SPECT) to identify differences between ET and tremor-dominant Parkinson's disease (TPD). We recruited 33 patients with TPD, 16 patients with ET, and 33 healthy controls. We compared the severity of tremor symptoms by comparing the Fahn-Tolosa-Marin rating scale (FTM) score and the tremor score from Unified Parkinson's Disease Rating Scale (UPDRS) between TPD and ET patients. Subjects were evaluated by neuropsychological assessments, MRI and perfusion SPECT of the brain. Total FTM score was significantly higher in ET patients than TPD patients. However, there was no significant difference in FTM Part A scores between the two patient groups, while the scores for FTM Part B and C were significantly higher in ET patients than TPD patients. Brain SPECT analysis of the TPD group demonstrated significant hypoperfusion of both the lentiform nucleus and thalamus compared to the ET group. Brain perfusion SPECT may be a useful clinical method to differentiate between TPD and ET even during early-phase PD, because the lentiform nucleus and thalamus show differences in regional perfusion between these two groups during this time period. Additionally, we found evidence of cerebellar dysfunction in both TPT and ET. Copyright © 2014 Elsevier Ltd. All rights reserved.

Posterolateral Trajectories Favor a Longer Motor Domain in Subthalamic Nucleus Deep Brain Stimulation for Parkinson Disease.

PubMed

Tamir, Idit; Marmor-Levin, Odeya; Eitan, Renana; Bergman, Hagai; Israel, Zvi

2017-10-01

The clinical outcome of patients with Parkinson disease (PD) who undergo subthalamic nucleus (STN) deep brain stimulation (DBS) is, in part, determined by the length of the electrode trajectory through the motor STN domain, the dorsolateral oscillatory region (DLOR). Trajectory length has been found to correlate with the stimulation-related improvement in patients' motor function (estimated by part III of the United Parkinson's Disease Rating Scale [UPDRS]). Therefore, it seems that ideally trajectories should have maximal DLOR length. We retrospectively studied the influence of various anatomic aspects of the brains of patients with PD and the geometry of trajectories planned on the length of the DLOR and STN recorded during DBS surgery. We examined 212 trajectories and 424 microelectrode recording tracks in 115 patients operated on in our center between 2010 and 2015. We found a strong correlation between the length of the recorded DLOR and STN. Trajectories that were more lateral and/or posterior in orientation had a longer STN and DLOR pass, although the DLOR/STN fraction length remained constant. The STN target was more lateral when the third ventricle was wider, and the latter correlated with older age and male gender. Trajectory angles correlate with the recorded STN and DLOR lengths, and should be altered toward a more posterolateral angle in older patients and atrophied brains to compensate for the changes in STN location and geometry. These fine adjustments should yield a longer motor domain pass, thereby improving the patient's predicted outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

Factors associated with falling in early, treated Parkinson's disease: The NET-PD LS1 cohort.

PubMed

Chou, Kelvin L; Elm, Jordan J; Wielinski, Catherine L; Simon, David K; Aminoff, Michael J; Christine, Chadwick W; Liang, Grace S; Hauser, Robert A; Sudarsky, Lewis; Umeh, Chizoba C; Voss, Tiffini; Juncos, Jorge; Fang, John Y; Boyd, James T; Bodis-Wollner, Ivan; Mari, Zoltan; Morgan, John C; Wills, Anne-Marie; Lee, Stephen L; Parashos, Sotirios A

2017-06-15

Recognizing the factors associated with falling in Parkinson's disease (PD) would improve identification of at-risk individuals. To examine frequency of falling and baseline characteristics associated with falling in PD using the National Institute of Neurological Disorders and Stroke (NINDS) Exploratory Trials in PD Long-term Study-1 (NET-PD LS-1) dataset. The LS-1 database included 1741 early treated PD subjects (median 4year follow-up). Baseline characteristics were tested for a univariate association with post-baseline falling during the trial. Significant variables were included in a multivariable logistic regression model. A separate analysis using a negative binomial model investigated baseline factors on fall rate. 728 subjects (42%) fell during the trial, including at baseline. A baseline history of falls was the factor most associated with post-baseline falling. Men had lower odds of post-baseline falling compared to women, but for men, the probability of a post-baseline fall increased with age such that after age 70, men and women had similar odds of falling. Other baseline factors associated with a post-baseline fall and increased fall rate included the Unified PD Rating Scale (UPDRS) Activities of Daily Living (ADL) score, total functional capacity (TFC), baseline ambulatory capacity score and dopamine agonist monotherapy. Falls are common in early treated PD. The biggest risk factor for falls in PD remains a history of falling. Measures of functional ability (UPDRS ADL, TFC) and ambulatory capacity are novel clinical risk factors needing further study. A significant age by sex interaction may help to explain why age has been an inconsistent risk factor for falls in PD. Copyright © 2017 Elsevier B.V. All rights reserved.

Management of postural sensory conflict and dynamic balance control in late-stage Parkinson's disease.

PubMed

Colnat-Coulbois, S; Gauchard, G C; Maillard, L; Barroche, G; Vespignani, H; Auque, J; Perrin, P P

2011-10-13

Parkinson's disease (PD) is known to affect postural control, especially in situations needing a change in balance strategy or when a concurrent task is simultaneously performed. However, few studies assessing postural control in patients with PD included homogeneous population in late stage of the disease. Thus, this study aimed to analyse postural control and strategies in a homogeneous population of patients with idiopathic advanced (late-stage) PD, and to determine the contribution of peripheral inputs in simple and more complex postural tasks, such as sensory conflicting and dynamic tasks. Twenty-four subjects with advanced PD (duration: median (M)=11.0 years, interquartile range (IQR)=4.3 years; Unified Parkinson's Disease Rating Scale (UPDRS): M "on-dopa"=13.5, IQR=7.8; UPDRS: M "off-dopa"=48.5, IQR=16.8; Hoehn and Yahr stage IV in all patients) and 48 age-matched healthy controls underwent static (SPT) and dynamic posturographic (DPT) tests and a sensory organization test (SOT). In SPT, patients with PD showed reduced postural control precision with increased oscillations in both anterior-posterior and medial-lateral planes. In SOT, patients with PD displayed reduced postural performances especially in situations in which visual and vestibular cues became predominant to organize balance control, as was the ability to manage balance in situations for which visual or proprioceptive inputs are disrupted. In DPT, postural restabilization strategies were often inefficient to maintain equilibrium resulting in falls. Postural strategies were often precarious, postural regulation involving more hip joint than ankle joint in patients with advanced PD than in controls. Difficulties in managing complex postural situations, such as sensory conflicting and dynamic situations might reflect an inadequate sensory organization suggesting impairment in central information processing. Copyright © 2011. Published by Elsevier Ltd.

Prodromal Parkinsonism and Neurodegenerative Risk Stratification in REM Sleep Behavior Disorder

PubMed Central

Lawton, Michael; Rolinski, Michal; Evetts, Samuel; Baig, Fahd; Ruffmann, Claudio; Gornall, Aimie; Klein, Johannes C; Lo, Christine; Dennis, Gary; Bandmann, Oliver; Quinnell, Timothy; Zaiwalla, Zenobia; Ben-Shlomo, Yoav; Hu, Michele TM

2017-01-01

Abstract Objectives Rapid eye movement (REM) sleep behavior disorder (RBD) is the most specific marker of prodromal alpha-synucleinopathies. We sought to delineate the baseline clinical characteristics of RBD and evaluate risk stratification models. Methods Clinical assessments were performed in 171 RBD, 296 control, and 119 untreated Parkinson’s (PD) participants. Putative risk measures were assessed as predictors of prodromal neurodegeneration, and Movement Disorders Society (MDS) criteria for prodromal PD were applied. Participants were screened for common leucine-rich repeat kinase 2 (LRRK2)/glucocerebrosidase gene (GBA) gene mutations. Results Compared to controls, participants with RBD had higher rates of solvent exposure, head injury, smoking, obesity, and antidepressant use. GBA mutations were more common in RBD, but no LRRK2 mutations were found. RBD participants performed significantly worse than controls on Unified Parkinson’s Disease Rating Scale (UPDRS)-III, timed “get-up-and-go”, Flamingo test, Sniffin Sticks, and cognitive tests and had worse measures of constipation, quality of life (QOL), and orthostatic hypotension. For all these measures except UPDRS-III, RBD and PD participants were equally impaired. Depression, anxiety, and apathy were worse in RBD compared to PD participants. Stratification of people with RBD according to antidepressant use, obesity, and age altered the odds ratio (OR) of hyposmia compared to controls from 3.4 to 45.5. 74% (95% confidence interval [CI] 66%, 80%) of RBD participants met the MDS criteria for probable prodromal Parkinson’s compared to 0.3% (95% CI 0.009%, 2%) of controls. Conclusions RBD are impaired across a range of clinical measures consistent with prodromal PD and suggestive of a more severe nonmotor subtype. Clinical risk stratification has the potential to select higher risk patients for neuroprotective interventions. PMID:28472425

Can therapeutic Thai massage improve upper limb muscle strength in Parkinson's disease? An objective randomized-controlled trial.

PubMed

Miyahara, Yuka; Jitkritsadakul, Onanong; Sringean, Jirada; Aungkab, Nicharee; Khongprasert, Surasa; Bhidayasiri, Roongroj

2018-04-01

Muscle weakness is a frequent complaint amongst Parkinson's disease (PD) patients. However, evidence-based therapeutic options for this symptom are limited. We objectively measure the efficacy of therapeutic Thai massage (TTM) on upper limb muscle strength, using an isokinetic dynamometer. A total of 60 PD patients with muscle weakness that is not related to their 'off' periods or other neurological causes were equally randomized to TTM intervention (n = 30), consisting of six TTM sessions over a 3-week period, or standard medical care (no intervention, n = 30). Primary outcomes included peak extension and flexion torques. Scale-based outcomes, including Unified Parkinson's Disease Rating Scale (UPDRS) and visual analogue scale for pain (VAS) were also performed. From baseline to end of treatment, patients in the intervention group showed significant improvement on primary objective outcomes, including peak flexion torque (F = 30.613, p  < .001) and peak extension torque (F = 35.569, p  < .001) and time to maximal flexion speed (F = 14.216, p  = .001). Scale-based assessments mirrored improvements in the objective outcomes with a significant improvement from baseline to end of treatment of the UPDRS-bradykinesia of a more affected upper limb (F = 9.239, p  = .005), and VAS (F = 69.864, p  < .001) following the TTM intervention, compared to the control group. No patients reported adverse events in association with TTM. Our findings provide objective evidence that TTM used in combination with standard medical therapies is effective in improving upper limb muscle strength in patients with PD. Further studies are needed to determine the efficacy of TTM on other motor and non-motor symptoms in PD.

Tracking Parkinson's: Study Design and Baseline Patient Data.

PubMed

Malek, Naveed; Swallow, Diane M A; Grosset, Katherine A; Lawton, Michael A; Marrinan, Sarah L; Lehn, Alexander C; Bresner, Catherine; Bajaj, Nin; Barker, Roger A; Ben-Shlomo, Yoav; Burn, David J; Foltynie, Thomas; Hardy, John; Morris, Huw R; Williams, Nigel M; Wood, Nicholas; Grosset, Donald G

2015-01-01

There is wide variation in the phenotypic expression of Parkinson's disease (PD), which is driven by both genetic and epidemiological influences. To define and explain variation in the clinical phenotype of PD, in relation to genotypic variation. Tracking Parkinson's is a multicentre prospective longitudinal epidemiologic and biomarker study of PD. Patients attending specialist clinics in the United Kingdom with recent onset (<3.5 years) and young onset (diagnosed <50 years of age) PD were enrolled. Motor, non-motor and quality of life assessments were performed using validated scales. Cases are followed up 6 monthly up to 4.5 years for recent onset PD, and up to 1 year for young onset PD. We present here baseline clinical data from this large and demographically representative cohort. 2247 PD cases were recruited (1987 recent onset, 260 young onset). Recent onset cases had a mean (standard deviation, SD) age of 67.6 years (9.3) at study entry, 65.7% males, with disease duration 1.3 years (0.9), MDS-UPDRS 3 scores 22.9 (12.3), LEDD 295 mg/day (211) and PDQ-8 score 5.9 (4.8). Young onset cases were 53.5 years old (7.8) at study entry, 66.9% male, with disease duration 10.2 years (6.7), MDS-UPDRS 3 scores 27.4 (15.3), LEDD 926 mg/day (567) and PDQ-8 score 11.6 (6.1). We have established a large clinical PD cohort, consisting of young onset and recent onset cases, which is designed to evaluate variation in clinical expression, in relation to genetic influences, and which offers a platform for future imaging and biomarker research.

The reorganization of functional architecture in the early-stages of Parkinson's disease.

PubMed

Tuovinen, Noora; Seppi, Klaus; de Pasquale, Francesco; Müller, Christoph; Nocker, Michael; Schocke, Michael; Gizewski, Elke R; Kremser, Christian; Wenning, Gregor K; Poewe, Werner; Djamshidian, Atbin; Scherfler, Christoph; Seki, Morinobu

2018-05-01

The study aim was to identify longitudinal abnormalities of functional connectivity and its relation with motor disability in early to moderately advanced stages of Parkinson's disease patients. 3.0T structural and resting-state functional MRI was performed in healthy subjects (n = 16) and Parkinson's disease patients (n = 16) with mean disease duration of 2.2 ± 1.2 years at baseline with a clinical follow-up of 1.5 ± 0.3 years. Resting-state fMRI analysis included region-to-region connectivity in correlation with UPDRS-III scores and computation of Global Efficiency and Degree Centrality. At baseline, patients' connectivity increased between the cerebellum and somatomotor network, and decreased between motor regions (Rolandic operculum, precentral gyrus, supplementary motor area, postcentral gyrus) and cingulate connectivity. At 1.5 years follow-up, connectivity remained altered in the same regions identified at baseline. The cerebellum showed additional hyperconnectivity within itself and to the caudate nucleus, thalamus and amygdala compared to controls. These differences correlated with UPDRS-III scores. Seed-based connectivity revealed increased involvement of the default mode network with precentral gyrus in patients at follow-up investigation. Resting-state fMRI identified marked disturbances of the overall architecture of connectivity in Parkinson's disease. The noted alterations in cortical motor areas were associated with cerebellar hyperconnectivity in early to moderately advanced stages of Parkinson's disease suggesting ongoing attempts of recovery and compensatory mechanism for affected functions. The potential to identify connectivity alterations in regions related to both motor and attentional functions requires further evaluation as an objective marker to monitor disease progression, and medical, as well as surgical interventions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Parkinson Disease Phenotype in Ashkenazi Jews with and without LRRK2 G2019S mutations

PubMed Central

Alcalay, Roy N.; Mirelman, Anat; Saunders-Pullman, Rachel; Tang, Ming-X; Santana, Helen Mejia; Raymond, Deborah; Roos, Ernest; Orbe-Reilly, Martha; Gurevich, Tanya; Shira, Anat Bar; Weisz, Mali Gana; Yasinovsky, Kira; Zalis, Maayan; Thaler, Avner; Deik, Andres; Barrett, Matthew James; Cabassa, Jose; Groves, Mark; Hunt, Ann L.; Lubarr, Naomi; Luciano, Marta San; Miravite, Joan; Palmese, Christina; Sachdev, Rivka; Sarva, Harini; Severt, Lawrence; Shanker, Vicki; Swan, Matthew Carrington; Soto-Valencia, Jeannie; Johannes, Brooke; Ortega, Robert; Fahn, Stanley; Cote, Lucien; Waters, Cheryl; Mazzoni, Pietro; Ford, Blair; Louis, Elan; Levy, Oren; Rosado, Llency; Ruiz, Diana; Dorovski, Tsvyatko; Pauciulo, Michael; Nichols, William; Orr-Urtreger, Avi; Ozelius, Laurie; Clark, Lorraine; Giladi, Nir; Bressman, Susan; Marder, Karen S

2013-01-01

Background The phenotype of Parkinson disease (PD) patients with and without LRRK2 G2019S mutations is reported to be similar; however large uniformly evaluated series are lacking. Objective To characterize the clinical phenotype of Ashkenazi Jewish (AJ) PD carriers of the LRRK2 G2019S mutation. Methods We studied 553 AJ PD patients, including 65 patients who were previously reported, from three sites (two in New York and one in Tel-Aviv). GBA mutation carriers were excluded. Evaluations included the Montreal Cognitive Assessment (MoCA), the Unified Parkinson's Disease Rating Scale (UPDRS), the geriatric depression scale (GDS) and the non-motor symptoms (NMS) questionnaire. Regression models were constructed to test the association between clinical and demographic features and LRRK2 status (outcome) in 488 newly recruited participants. Results LRRK2 G2019S carriers (n=97) and non-carriers (n=391) were similar in age and age-at-onset of PD. Carriers had longer disease duration (8.6years versus 6.1years, p<0.001), were more likely to be women (51.5% versus 37.9%, p=0.015) and more often reported first symptoms in lower extremities (40.0% versus 19.2%, p<0.001). In logistic models adjusted for age, disease duration, gender, education, and site, carriers were more likely to have lower extremity onset (p<0.001), postural instability gait difficulty (PIGD, p=0.043) and persistent levodopa response for>5 years (p=0.042). Performance on UPDRS, MoCA, GDS and NMS did not differ by mutation status. Conclusion PD in AJ-LRRK2 G2019S mutation carriers is similar to idiopathic PD, but characterized by more frequent lower extremity involvement at onset and PIGD without the associated cognitive impairment. PMID:24243757

Neurotransmitter activity is linked to outcome following subthalamic deep brain stimulation in Parkinson's disease.

PubMed

O'Gorman Tuura, Ruth L; Baumann, Christian R; Baumann-Vogel, Heide

2018-05-01

While the mechanisms underlying the therapeutic effects of deep brain stimulation (DBS) in Parkinson's Disease (PD) are not yet fully understood, DBS appears to exert a wide range of neurochemical effects on the network level, thought to arise from activation of inhibitory and excitatory pathways. The activity within the primary inhibitory (GABAergic) and excitatory (glutamatergic) neurotransmitter systems may therefore play an important role in the therapeutic efficacy of DBS in PD. The purpose of this study was to investigate abnormalities in GABA-ergic and glutamatergic neurotransmission in PD, and to examine the link between neurotransmitter levels and outcome following DBS. Magnetic resonance spectra were acquired from the pons and basal ganglia in sixteen patients with PD and sixteen matched control participants. GABA and glutamate levels were quantified with LCModel, an automated spectral fitting package. Fourteen patients subsequently underwent DBS, and PD symptoms were evaluated with the MDS-UPDRS at baseline and six months after surgery. The efficacy of DBS treatment was evaluated from the percentage improvement in MDS-UPDRS scores. Basal ganglia GABA levels were significantly higher in PD patients relative to control participants (p < 0.01), while pontine glutamate + glutamine (Glx) levels were significantly lower in patients with PD (p < 0.05). While GABA levels were not significantly related to outcome post-surgery, basal ganglia glutamate levels emerged as a significant predictor of outcome, suggesting a possible role for glutamatergic neurotransmission in the therapeutic mechanism of DBS. GABAergic and glutamatergic neurotransmission is altered in PD, and glutamatergic activity in particular may influence outcome post-surgery. Copyright © 2018 Elsevier Ltd. All rights reserved.

Extended "Timed Up and Go" assessment as a clinical indicator of cognitive state in Parkinson's disease.

PubMed

Evans, Tess; Jefferson, Alexa; Byrnes, Michelle; Walters, Sue; Ghosh, Soumya; Mastaglia, Frank L; Power, Brian; Anderton, Ryan S

2017-04-15

To evaluate a modified extended Timed Up and Go (extended-TUG) assessment against a panel of validated clinical assessments, as an indicator of Parkinson's disease (PD) severity and cognitive impairment. Eighty-seven participants with idiopathic PD were sequentially recruited from a Movement Disorders Clinic. An extended-TUG assessment was employed which required participants to stand from a seated position, walk in a straight line for 7m, turn 180° and then return to the start, in a seated position. The extended-TUG assessment duration was correlated to a panel of clinical assessments, including the Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Quality of Life (PDQ-39), Scales for Outcomes in Parkinson's Disease (SCOPA-Cog), revised Addenbrooke's Cognitive Index (ACE-R) and Barratt's Impulsivity Scale 11 (BIS-11). Extended-TUG time was significantly correlated to MDS-UPDRS III score and to SCOPA-Cog, ACE-R (p<0.001) and PDQ-39 scores (p<0.01). Generalized linear models determined the extended-TUG to be a sole variable in predicting ACE-R or SCOPA-Cog scores. Patients in the fastest extended-TUG tertile were predicted to perform 8.3 and 13.4 points better in the SCOPA-Cog and ACE-R assessments, respectively, than the slowest group. Patients who exceeded the dementia cut-off scores with these instruments exhibited significantly longer extended-TUG times. Extended-TUG performance appears to be a useful indicator of cognition as well as motor function and quality of life in PD, and warrants further evaluation as a first line assessment tool to monitor disease severity and response to treatment. Poor extended-TUG performance may identify patients without overt cognitive impairment form whom cognitive assessment is needed. Copyright © 2017 Elsevier B.V. All rights reserved.

Blink rate is associated with drug-induced parkinsonism in patients with severe mental illness, but does not meet requirements to serve as a clinical test: the Curacao extrapyramidal syndromes study XIII.

PubMed

Mentzel, Charlotte L; Bakker, P Roberto; van Os, Jim; Drukker, Marjan; Matroos, Glenn E; Tijssen, Marina A J; van Harten, Peter N

2017-08-25

Drug-induced parkinsonism (DIP) has a high prevalence and is associated with poorer quality of life. To find a practical clinical tool to assess DIP in patients with severe mental illness (SMI), the association between blink rate and drug-induced parkinsonism (DIP) was assessed. In a cohort of 204 SMI patients receiving care from the only mental health service of the previous Dutch Antilles, blink rate per minute during conversation was assessed by an additional trained movement disorder specialist. DIP was rated on the Unified Parkinson's Disease Rating Scale (UPDRS) in 878 assessments over a period of 18 years. Diagnostic values of blink rate were calculated. DIP prevalence was 36%, average blink rate was 14 (standard deviation (SD) 11) for patients with DIP, and 19 (SD 14) for patients without. There was a significant association between blink rate and DIP (p < 0.001). With a blink rate cut-off of 20 blinks per minute, sensitivity was 77% and specificity was 38%. A 10% percentile cut-off model resulted in an area under the ROC curve of 0.61. A logistic prediction model between dichotomous DIP and continuous blink rate per minute an area under the ROC curve of 0.70. There is a significant association between blink rate and DIP as diagnosed on the UPDRS. However, blink rate sensitivity and specificity with regard to DIP are too low to replace clinical rating scales in routine psychiatric practice. The study was started over 20 years ago in 1992, at the time registering a trial was not common practice, therefore the study was never registered.

A Validation Study of a Smartphone-Based Finger Tapping Application for Quantitative Assessment of Bradykinesia in Parkinson’s Disease

PubMed Central

Lee, Chae Young; Kang, Seong Jun; Hong, Sang-Kyoon

2016-01-01

Background Most studies of smartphone-based assessments of motor symptoms in Parkinson’s disease (PD) focused on gait, tremor or speech. Studies evaluating bradykinesia using wearable sensors are limited by a small cohort size and study design. We developed an application named smartphone tapper (SmT) to determine its applicability for clinical purposes and compared SmT parameters to current standard methods in a larger cohort. Methods A total of 57 PD patients and 87 controls examined with motor UPDRS underwent timed tapping tests (TT) using SmT and mechanical tappers (MeT) according to CAPSIT-PD. Subjects were asked to alternately tap each side of two rectangles with an index finger at maximum speed for ten seconds. Kinematic measurements were compared between the two groups. Results The mean number of correct tapping (MCoT), mean total distance of finger movement (T-Dist), mean inter-tap distance, and mean inter-tap dwelling time (IT-DwT) were significantly different between PD patients and controls. MCoT, as assessed using SmT, significantly correlated with motor UPDRS scores, bradykinesia subscores and MCoT using MeT. Multivariate analysis using the SmT parameters, such as T-Dist or IT-DwT, as predictive variables and age and gender as covariates demonstrated that PD patients were discriminated from controls. ROC curve analysis of a regression model demonstrated that the AUC for T-Dist was 0.92 (95% CI 0.88–0.96). Conclusion Our results suggest that a smartphone tapping application is comparable to conventional methods for the assessment of motor dysfunction in PD and may be useful in clinical practice. PMID:27467066

Intermittent theta-burst transcranial magnetic stimulation for treatment of Parkinson disease

PubMed Central

Berman, B.D.; Houdayer, E.; Pal, N.; Luckenbaugh, D.A.; Schneider, L.; Miranda, S.; Hallett, M.

2011-01-01

Objective: To investigate the safety and efficacy of intermittent theta-burst stimulation (iTBS) in the treatment of motor symptoms in Parkinson disease (PD). Background: Progression of PD is characterized by the emergence of motor deficits, which eventually respond less to dopaminergic therapy and pose a therapeutic challenge. Repetitive transcranial magnetic stimulation (rTMS) has shown promising results in improving gait, a major cause of disability, and may provide a therapeutic alternative. iTBS is a novel type of rTMS that may be more efficacious than conventional rTMS. Methods: In this randomized, double-blind, sham-controlled study, we investigated safety and efficacy of iTBS of the motor and dorsolateral prefrontal cortices in 8 sessions over 2 weeks (evidence Class I). Assessment of safety and clinical efficacy over a 1-month period included timed tests of gait and bradykinesia, Unified Parkinson's Disease Rating Scale (UPDRS), and additional clinical, neuropsychological, and neurophysiologic measures. Results: We investigated 26 patients with mild to moderate PD: 13 received iTBS and 13 sham stimulation. We found beneficial effects of iTBS on mood, but no improvement of gait, bradykinesia, UPDRS, and other measures. EEG/EMG monitoring recorded no pathologic increase of cortical excitability or epileptic activity. Few reported discomfort or pain and one experienced tinnitus during real stimulation. Conclusion: iTBS of the motor and prefrontal cortices appears safe and improves mood, but failed to improve motor performance and functional status in PD. Classification of evidence: This study provides Class I evidence that iTBS was not effective for gait, upper extremity bradykinesia, or other motor symptoms in PD. PMID:21321333

Speech and Voice Response to a Levodopa Challenge in Late-Stage Parkinson's Disease.

PubMed

Fabbri, Margherita; Guimarães, Isabel; Cardoso, Rita; Coelho, Miguel; Guedes, Leonor Correia; Rosa, Mario M; Godinho, Catarina; Abreu, Daisy; Gonçalves, Nilza; Antonini, Angelo; Ferreira, Joaquim J

2017-01-01

Parkinson's disease (PD) patients are affected by hypokinetic dysarthria, characterized by hypophonia and dysprosody, which worsens with disease progression. Levodopa's (l-dopa) effect on quality of speech is inconclusive; no data are currently available for late-stage PD (LSPD). To assess the modifications of speech and voice in LSPD following an acute l-dopa challenge. LSPD patients [Schwab and England score <50/Hoehn and Yahr stage >3 (MED ON)] performed several vocal tasks before and after an acute l-dopa challenge. The following was assessed: respiratory support for speech, voice quality, stability and variability, speech rate, and motor performance (MDS-UPDRS-III). All voice samples were recorded and analyzed by a speech and language therapist blinded to patients' therapeutic condition using Praat 5.1 software. 24/27 (14 men) LSPD patients succeeded in performing voice tasks. Median age and disease duration of patients were 79 [IQR: 71.5-81.7] and 14.5 [IQR: 11-15.7] years, respectively. In MED OFF, respiratory breath support and pitch break time of LSPD patients were worse than the normative values of non-parkinsonian. A correlation was found between disease duration and voice quality ( R  = 0.51; p  = 0.013) and speech rate ( R  = -0.55; p  = 0.008). l-Dopa significantly improved MDS-UPDRS-III score (20%), with no effect on speech as assessed by clinical rating scales and automated analysis. Speech is severely affected in LSPD. Although l-dopa had some effect on motor performance, including axial signs, speech and voice did not improve. The applicability and efficacy of non-pharmacological treatment for speech impairment should be considered for speech disorder management in PD.

Predictors of weight loss in early treated Parkinson's disease from the NET-PD LS-1 cohort.

PubMed

Wills, Anne-Marie; Li, Ruosha; Pérez, Adriana; Ren, Xuehan; Boyd, James

2017-08-01

Weight loss is a common symptom of Parkinson's disease and is associated with impaired quality of life. Predictors of weight loss have not been studied in large clinical cohorts. We previously observed an association between change in body mass index and change in Unified Parkinson's Disease Rating Scale (UPDRS) motor and total scores. In this study, we performed a secondary analysis of longitudinal data (1-6 years) from 1619 participants in the NINDS Exploratory Trials in PD Long-term Study-1 (NET-PD LS1) to explore predictors of weight loss in a large prospective clinical trial cohort of early treated Parkinson's disease. The NET-PD LS1 study was a double-blind randomized placebo controlled clinical trial of creatine monohydrate 10 gm/day in early treated PD (within 5 years of diagnosis and within 2 years of starting dopaminergic medications). Linear mixed models were used to estimate the effect of baseline clinical covariates on weight change over time. On average, participants lost only 0.6 kg per year. Higher age, baseline weight, female gender, higher baseline UPDRS scores, greater postural instability, difficulty eating and drinking, lower cognitive scores and baseline levodopa use (compared to dopamine agonists) were all associated with weight loss. Surprisingly baseline difficulty swallowing, dyskinesia, depression, intestinal hypomotility (constipation) and self-reported nausea/vomiting/anorexia were not significantly associated with weight loss in this cohort of early treated Parkinson's disease patients. On average, participants with Parkinson's disease experience little weight loss during the first 1-6 years after starting dopaminergic replacement therapy, however levodopa use and postural instability were both predictors of early weight loss. Trial Registration clinicaltrials.gov identifier# NCT00449865.

Urate predicts rate of clinical decline in Parkinson disease

PubMed Central

Ascherio, Alberto; LeWitt, Peter A.; Xu, Kui; Eberly, Shirley; Watts, Arthur; Matson, Wayne R.; Marras, Connie; Kieburtz, Karl; Rudolph, Alice; Bogdanov, Mikhail B.; Schwid, Steven R.; Tennis, Marsha; Tanner, Caroline M.; Beal, M. Flint; Lang, Anthony E.; Oakes, David; Fahn, Stanley; Shoulson, Ira; Schwarzschild, Michael A.

2009-01-01

Context The risk of Parkinson disease (PD) and its rate of progression may decline with increasing blood urate, a major antioxidant. Objective To determine whether serum and cerebrospinal fluid (CSF) concentrations of urate predict clinical progression in patients with PD. Design, Setting, and Participants 800 subjects with early PD enrolled in the DATATOP trial. Pre-treatment urate was measured in serum for 774 subjects and in CSF for 713. Main Outcome Measures Treatment-, age- and sex-adjusted hazard ratios (HRs) for clinical disability requiring levodopa therapy, the pre-specified primary endpoint. Results The HR of progressing to endpoint decreased with increasing serum urate (HR for 1 standard deviation increase = 0.82; 95% CI = 0.73 to 0.93). In analyses stratified by α-tocopherol treatment (2,000 IU/day), a decrease in the HR for the primary endpoint was seen only among subjects not treated with α-tocopherol (HR = 0.75; 95% CI = 0.62 to 0.89, versus those treated HR = 0.90; 95% CI = 0.75 to 1.08). Results were similar for the rate of change in the United Parkinson Disease Rating Scale (UPDRS). CSF urate was also inversely related to both the primary endpoint (HR for highest versus lowest quintile = 0.65; 95% CI: 0.54 to 0.96) and to the rate of change in UPDRS. As with serum urate, these associations were present only among subjects not treated with α-tocopherol. Conclusion Higher serum and CSF urate at baseline were associated with slower rates of clinical decline. The findings strengthen the link between urate and PD and the rationale for considering CNS urate elevation as a potential strategy to slow PD progression. PMID:19822770

The impact of high intensity physical training on motor and non-motor symptoms in patients with Parkinson's disease (PIP): a preliminary study.

PubMed

Morberg, Bo M; Jensen, Joakim; Bode, Matthias; Wermuth, Lene

2014-01-01

Parkinson's disease (PD) is a neurodegenerative disease caused by loss of dopaminergic nigrostriatal neurons. Several studies have investigated various physical interventions on PD. The effects of a high intensity exercise program with focus on resistance; cardio; equilibrium; and flexibility training have not been evaluated previously. The aim of this study was to investigate the effects of a complex, high intensity physical training program, with a long duration, on motor and non-motor symptoms in patients with PD. 24 patients with PD Hoehn and Yahr stage 1-3 were non-randomly allocated to an intervention group (n = 12) and a control group (n = 12). The intervention group underwent 32 weeks of high intensity personalized physical training twice a week, with an optional extra training session once a week. The control group received general recommendations regarding physical activity. The primary outcomes were the change in Unified Parkinson's Disease Rating Scale Subscores (UPDRS) and the Parkinson's Disease Questionnaire (PDQ-39). At week 32, the training significantly improved both UPDRS motor subscores (p = 0.045), activities of daily living subscores (ADL) (p = 0.006), mentation subscores (p = 0.004) and complication subscores (p = 0.019). The effect on the PDQ39 total score was not statistically significant. The intervention group however experienced a substantial improvement of the PDQ39 items emotional well-being (-11.0) and bodily discomfort (-7.14). The results suggest that a personal high intensity exercise program may favorably influence both motor and non-motor symptoms in patients with mild to moderate PD. More studies with both higher methodology in study design and a follow-up examination are recommended.

Falls in ambulatory non-demented patients with Parkinson's disease.

PubMed

Rascol, Olivier; Perez-Lloret, Santiago; Damier, Philippe; Delval, Arnaud; Derkinderen, Pascal; Destée, Alain; Meissner, Wassilios G; Tison, Francois; Negre-Pages, Laurence

2015-10-01

This study aimed at determining the prevalence of falling in PD patients, to assess generic and disease-specific clinical and pharmacological factors, relationship with health-related quality of life (HR-QoL) and changes in falls from OFF to ON in patients with motor fluctuations. Six-hundred and eighty-three PD patients of the COPARK survey were evaluated (11 had missing data and were excluded from the analysis). Patients with falls were identified as those with a UPDRS Item 13 ≥ 1 in the ON condition. All patients were assessed in a standardized manner [demographics, treatments, Unified PD Rating Scale (UPDRS), Hospital Anxiety and Depression Scale, Pittsburg questionnaire and HR-QoL scales (SF36, PDQ39)]. Falling was reported by 108/672 (16%) PD patients during the ON state and prevalence increased according to PD severity, from 5% in Hoehn and Yahr stage 1-60% in stage 4. Falling was significantly related to lower HR-QoL. Falling correlated with (1) generic factors such as female gender, age at the end of academic studies and diuretics consumption, (2) motor PD-specific factors including disease severity, frozen gait, difficulties when arising from a chair, dyskinesia and higher levodopa daily equivalent dose and (3) non-motor PD-specific factors such as orthostatic hypotension and hallucinations. Falling was more frequent in OFF than in ON in 48/74 (64%) patients with motor fluctuations and remained unchanged in 27 patients (36%). In summary, falling affected a significant proportion of PD patients, especially in advanced stages. It was associated with a variety of generic and PD-specific factors and was related to reduced HR-QoL.

Clinical and Cognitive Phenotype of Mild Cognitive Impairment Evolving to Dementia with Lewy Bodies

PubMed Central

Cagnin, Annachiara; Bussè, Cinzia; Gardini, Simona; Jelcic, Nela; Guzzo, Caterina; Gnoato, Francesca; Mitolo, Micaela; Ermani, Mario; Caffarra, Paolo

2015-01-01

Objective The aim of this study was to determine which characteristics could better distinguish dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) at the mild cognitive impairment (MCI) stage, with particular emphasis on visual space and object perception abilities. Methods Fifty-three patients with mild cognitive deficits that were eventually diagnosed with probable DLB (MCI-DLB: n = 25) and AD (MCI-AD: n = 28) at a 3-year follow-up were retrospectively studied. At the first visit, the patients underwent cognitive assessment including the Qualitative Scoring Mini Mental State Examination Pentagon Test and the Visual Object and Space Perception Battery. The Neuropsychiatric Inventory Questionnaire, Unified Parkinson's Disease Rating Scale (UPDRS) and questionnaires for cognitive fluctuations and sleep disorders were also administered. Results The best clinical predictor of DLB was the presence of soft extrapyramidal signs (mean UPDRS score: 4.04 ± 5.9) detected in 72% of patients, followed by REM sleep behavior disorder (60%) and fluctuations (60%). Wrong performances in the pentagon's number of angles were obtained in 44% of DLB and 3.7% of AD patients and correlated with speed of visual attention. Executive functions, visual attention and visuospatial abilities were worse in DLB, while verbal episodic memory impairment was greater in AD. Deficits in the visual-perceptual domain were present in both MCI-DLB and AD. Conclusions Poor performance in the pentagon's number of angles is specific of DLB and correlates with speed of visual attention. The dorsal visual stream seems specifically more impaired in MCI-DLB with respect to the ventral visual stream, the latter being involved in both DLB and AD. These cognitive features, associated with subtle extrapyramidal signs, should alert clinicians to a diagnostic hypothesis of DLB. PMID:26674638

Different Alterations of Cerebral Regional Homogeneity in Early-Onset and Late-Onset Parkinson's Disease

PubMed Central

Sheng, Ke; Fang, Weidong; Zhu, Yingcheng; Shuai, Guangying; Zou, Dezhi; Su, Meilan; Han, Yu; Cheng, Oumei

2016-01-01

HIGHLIGHTS Eighteen EOPD, 21 LOPD and 37 age-matched normal control subjects participated in the resting state fMRI scans.Age at onset of PD modulates the distribution of cerebral regional homogeneity during resting state.Disproportionate putamen alterations are more prominent in PD patients with a younger age of onset. Objective: Early-onset Parkinson's disease (EOPD) is distinct from late-onset PD (LOPD) as it relates to the clinical profile and response to medication. The objective of current paper is to investigate whether characteristics of spontaneous brain activity in the resting state are associated with the age of disease onset. Methods: We assessed the correlation between neural activity and age-at-onset in a sample of 39 PD patients (18 EOPD and 21 LOPD) and 37 age-matched normal control subjects. Regional homogeneity (ReHo) approaches were employed using ANOVA with two factors: PD and age. Results: In the comparisons between LOPD and EOPD, EOPD revealed lower ReHo values in the right putamen and higher ReHo values in the left superior frontal gyrus. Compared with age-matched control subjects, EOPD exhibited lower ReHo values in the right putamen and higher ReHo values in the left inferior temporal gyrus; However, LOPD showed lower ReHo values in the right putamen and left insula. The ReHo values were negatively correlated with the UPDRS total scores in the right putamen in LOPD, but a correlation between the ReHo value and UPDRS score was not detected in EOPD. Conclusions: Our findings support the notion that age at onset is associated with the distribution of cerebral regional homogeneity in the resting state and suggest that disproportionate putamen alterations are more prominent in patients with a younger age of onset. PMID:27462265

Changes in postural control in patients with Parkinson's disease: a posturographic study.

PubMed

Doná, F; Aquino, C C; Gazzola, J M; Borges, V; Silva, S M C A; Ganança, F F; Caovilla, H H; Ferraz, H B

2016-09-01

Postural instability is one of the most disabling features in Parkinson's disease (PD), and often leads to falls that reduce mobility and functional capacity. The objectives of this study were to analyse the limit of stability (LOS) and influence of the manipulation of visual, somatosensorial and visual-vestibular information on postural control in patients with PD and healthy subjects. Cross-sectional. Movement Disorders Unit, university setting. Eighty-two subjects aged between 37 and 83 years: 41 with Parkinson's disease in the 'on' state and 41 healthy subjects with no neurological disorders. Both groups were matched in terms of sex and age. Unified Parkinson's Disease Rating Scale (UPDRS)-motor score, modified Hoehn and Yahr staging, Dynamic Gait Index (DGI) and posturography with integrated virtual reality. The parameters analysed by posturography were LOS area, area of body centre of pressure excursion and balance functional reserve in the standing position in 10 conditions (open and closed eyes, unstable surface with eyes closed, saccadic and optokinetic stimuli, and visual-vestibular interaction). The mean UPDRS motor score and DGI score were 27 [standard deviation (SD) 14] and 21 (SD 3), respectively. Thirteen participants scored between 0 and 19 points, indicating major risk of falls. Posturographic assessment showed that patients with PD had significantly lower LOS area and balance functional reserve values, and greater body sway area in all posturographic conditions compared with healthy subjects. Patients with PD have reduced LOS area and greater postural sway compared with healthy subjects. The deterioration in postural control was significantly associated with major risk of falls. Copyright © 2015 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Effectiveness of autogenic training in improving motor performances in Parkinson's disease.

PubMed

Ajimsha, M S; Majeed, Nisar A; Chinnavan, Elanchezhian; Thulasyammal, Ramiah Pillai

2014-06-01

Relaxation training can be an important adjunct in reducing symptoms associated with Parkinson's disease (PD). Autogenic Training (AT) is a simple, easily administered and inexpensive technique for retraining the mind and the body to be able to relax. AT uses visual imagery and body awareness to promote a state of deep relaxation. To investigate whether AT when used as an adjunct to Physiotherapy (PT) improves motor performances in PD in comparison with a control group receiving PT alone. Randomized, controlled, single blinded trial. Movement Disorder Clinic and Department of Physiotherapy, Sree Chithira Thirunal Institute of Medical Sciences and Technology in Trivandrum, Kerala, India. Patients with PD of grade 2 or 3 of Hoehn & Yahr (H&Y) scale (N = 66). AT group or control group. The techniques were administered by Physiotherapists trained in AT and consisted of 40 sessions per patient over 8 weeks. Motor score subscale of Unified Parkinson's Disease Rating Scale (UPDRS) was used to measure the motor performances. The primary outcome measure was the difference in Motor score subscale of UPDRS scores between Week 1 (pretest score), Week 8 (posttest score), and follow-up at Week 12 after randomization. The simple main effects analysis showed that the AT group performed better than the control group in weeks 8 and 12 (P < .005). Patients in the AT and control groups reported a 51.78% and 35.24% improvement, respectively, in their motor performances in Week 8 compared with that in Week 1, which persisted, in the follow-up (Week 12) as 30.82% in the AT group and 21.42% in the control group. This study provides evidence that AT when used as an adjunct to PT is more effective than PT alone in improving motor performances in PD patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Family Finance Education; An Interdisciplinary Approach. Volume II.

ERIC Educational Resources Information Center

Gibbs, Mary S., Ed.; And Others, Eds.

Volume II of a two-part series related to family finance education provides materials for study and discussion in the 1968 workshop. In Part I, members of the advisory council present their viewpoints concerning an interdisciplinary approach to education in family finance. Part II presents basic and current information related to principal areas…

10 CFR Appendix II to Part 960 - NRC and EPA Requirements for Preclosure Repository Performance

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false NRC and EPA Requirements for Preclosure Repository... SCREENING OF POTENTIAL SITES FOR A NUCLEAR WASTE REPOSITORY Pt. 960, App. II Appendix II to Part 960—NRC and EPA Requirements for Preclosure Repository Performance Under proposed 40 CFR part 191, subpart A...

A Dynamic Model of the Initial Spares Support List Development Process

DTIC Science & Technology

1979-06-01

S117Z1NOTE NREI -NOT READI END ITERS IIT7INOTE GPEI -QUANTITY OF PARTS M. END ITER 11775NOTE FUSERF -PARTS USE RATE FACTOR U8WOTE OP U -OTHER PARTS USE...FAILURES ’I 1675R PtJER.L=(NREI.K) (QPEI) (PUSERF.K)+OPUR II7HNOTE PUSER -PARTS USE RATE II7t5NOTE NREI -NOT READY END ITEMS II756NOTE GPEI -QUANTITY

46 CFR Appendix II to Part 153 - Metric Units Used in Part 153

Code of Federal Regulations, 2013 CFR

2013-10-01

.../cm2. ......do kPa 1×10 3 N/m 2. Temperature Degree Celsius °C 5/9 (°F-32). Viscosity milli-Pascal... 46 Shipping 5 2013-10-01 2013-10-01 false Metric Units Used in Part 153 II Appendix II to Part 153... common metric Force Newton N 0.225 lbs. Length Meter m 39.37 in. Centimeter cm .3937 in. Pressure Pascal...

46 CFR Appendix II to Part 153 - Metric Units Used in Part 153

Code of Federal Regulations, 2012 CFR

2012-10-01

.../cm2. ......do kPa 1×10 3 N/m 2. Temperature Degree Celsius °C 5/9 (°F-32). Viscosity milli-Pascal... 46 Shipping 5 2012-10-01 2012-10-01 false Metric Units Used in Part 153 II Appendix II to Part 153... common metric Force Newton N 0.225 lbs. Length Meter m 39.37 in. Centimeter cm .3937 in. Pressure Pascal...

46 CFR Appendix II to Part 153 - Metric Units Used in Part 153

Code of Federal Regulations, 2014 CFR

2014-10-01

.../cm2. ......do kPa 1×10 3 N/m 2. Temperature Degree Celsius °C 5/9 (°F-32). Viscosity milli-Pascal... 46 Shipping 5 2014-10-01 2014-10-01 false Metric Units Used in Part 153 II Appendix II to Part 153... common metric Force Newton N 0.225 lbs. Length Meter m 39.37 in. Centimeter cm .3937 in. Pressure Pascal...

78 FR 9057 - Medicare Program; Request for Information on the Use of Clinical Quality Measures (CQMs) Reported...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-07

... Part II: Lifelong Learning and Self-Assessment Part III: Cognitive Expertise Part IV: Practice...: Licensure and Professional Standing Part II: Lifelong Learning and Self-Assessment Part III: Cognitive...\\ The MOC assesses physicians' commitment to lifelong learning according to the following six core...

Amplitude-oriented exercise in Parkinson's disease: a randomized study comparing LSVT-BIG and a short training protocol.

PubMed

Ebersbach, Georg; Grust, Ute; Ebersbach, Almut; Wegner, Brigitte; Gandor, Florin; Kühn, Andrea A

2015-02-01

LSVT-BIG is an exercise for patients with Parkinson's disease (PD) comprising of 16 1-h sessions within 4 weeks. LSVT-BIG was compared with a 2-week short protocol (AOT-SP) consisting of 10 sessions with identical exercises in 42 patients with PD. UPDRS-III-score was reduced by -6.6 in LSVT-BIG and -5.7 in AOT-SP at follow-up after 16 weeks (p < 0.001). Measures of motor performance were equally improved by LSVT-BIG and AOT-SP but high-intensity LSVT-BIG was more effective to obtain patient-perceived benefit.

40 CFR Appendix II to Part 86 - Temperature Schedules

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 19 2010-07-01 2010-07-01 false Temperature Schedules II Appendix II... Appendix II to Part 86—Temperature Schedules (a) Ambient temperature cycle for the diurnal emission portion of the evaporative emission test (see § 86.133). Table I—Temperature Versus Time Sequence Use linear...

40 CFR Appendix II to Part 86 - Temperature Schedules

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 20 2013-07-01 2013-07-01 false Temperature Schedules II Appendix II... Appendix II to Part 86—Temperature Schedules (a) Ambient temperature cycle for the diurnal emission portion of the evaporative emission test (see § 86.133). Table I—Temperature Versus Time Sequence Use linear...

40 CFR Appendix II to Part 86 - Temperature Schedules

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 19 2011-07-01 2011-07-01 false Temperature Schedules II Appendix II... Appendix II to Part 86—Temperature Schedules (a) Ambient temperature cycle for the diurnal emission portion of the evaporative emission test (see § 86.133). Table I—Temperature Versus Time Sequence Use linear...

40 CFR Appendix II to Part 86 - Temperature Schedules

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 20 2012-07-01 2012-07-01 false Temperature Schedules II Appendix II... Appendix II to Part 86—Temperature Schedules (a) Ambient temperature cycle for the diurnal emission portion of the evaporative emission test (see § 86.133). Table I—Temperature Versus Time Sequence Use linear...

17 CFR 405.2 - Reports to be made by registered government securities brokers and dealers.

Code of Federal Regulations, 2010 CFR

2010-04-01

... government securities broker or dealer shall file Part I of Form BD-Y2K (§ 249.618 of this title) prepared as..., shall file Part II of Form BD-Y2K (§ 249.618 of this title). Part II of Form BD-Y2K shall address each... registered government securities broker or dealer that was not required to file Part II of Form BD-Y2K under...

Basic Services for Children: A Continuing Search for Learning Priorities. A Dossier for Initiating a Dialogue--Part II, 1978. Experiments and Innovations in Education No. 37.

ERIC Educational Resources Information Center

United Nations Educational, Scientific, and Cultural Organization, Paris (France).

Both parts I and II of the dossier are collections of selected activities directed toward the deprived young in a developing world. This book, part II, departs from its predecessor in that it takes a more global view of education services to both children and adults in developing countries. Part A discusses the philosophy and scope of the dossier.…

40 CFR Appendix III to Part 266 - Tier II Emission Rate Screening Limits for Free Chlorine and Hydrogen Chloride

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 28 2013-07-01 2013-07-01 false Tier II Emission Rate Screening Limits for Free Chlorine and Hydrogen Chloride III Appendix III to Part 266 Protection of Environment... to Part 266—Tier II Emission Rate Screening Limits for Free Chlorine and Hydrogen Chloride Terrain...

40 CFR Appendix III to Part 266 - Tier II Emission Rate Screening Limits for Free Chlorine and Hydrogen Chloride

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 27 2014-07-01 2014-07-01 false Tier II Emission Rate Screening Limits for Free Chlorine and Hydrogen Chloride III Appendix III to Part 266 Protection of Environment... to Part 266—Tier II Emission Rate Screening Limits for Free Chlorine and Hydrogen Chloride Terrain...

40 CFR Appendix III to Part 266 - Tier II Emission Rate Screening Limits for Free Chlorine and Hydrogen Chloride

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 27 2011-07-01 2011-07-01 false Tier II Emission Rate Screening Limits for Free Chlorine and Hydrogen Chloride III Appendix III to Part 266 Protection of Environment... to Part 266—Tier II Emission Rate Screening Limits for Free Chlorine and Hydrogen Chloride Terrain...

40 CFR Appendix III to Part 266 - Tier II Emission Rate Screening Limits for Free Chlorine and Hydrogen Chloride

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Tier II Emission Rate Screening Limits for Free Chlorine and Hydrogen Chloride III Appendix III to Part 266 Protection of Environment... to Part 266—Tier II Emission Rate Screening Limits for Free Chlorine and Hydrogen Chloride Terrain...

40 CFR Appendix III to Part 266 - Tier II Emission Rate Screening Limits for Free Chlorine and Hydrogen Chloride

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 28 2012-07-01 2012-07-01 false Tier II Emission Rate Screening Limits for Free Chlorine and Hydrogen Chloride III Appendix III to Part 266 Protection of Environment... to Part 266—Tier II Emission Rate Screening Limits for Free Chlorine and Hydrogen Chloride Terrain...

40 CFR Appendix II to Part 1054 - Duty Cycles for Laboratory Testing

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 32 2010-07-01 2010-07-01 false Duty Cycles for Laboratory Testing II.... 1054, App. II Appendix II to Part 1054—Duty Cycles for Laboratory Testing (a) Test handheld engines with the following steady-state duty cycle: G3 mode No. Engine speed a Torque(percent) b Weighting...

AT2 DS II - Accelerator System Design (Part II) - CCC Video Conference

ScienceCinema

None

2017-12-09

Discussion Session - Accelerator System Design (Part II) Tutors: C. Darve, J. Weisend II, Ph. Lebrun, A. Dabrowski, U. Raich Video Conference with the CERN Control Center. Experts in the field of Accelerator science will be available to answer the students questions. This session will link the CCC and SA (using Codec VC).

Subseabed disposal program annual report, January-December 1980. Volume II. Appendices (principal investigator progress reports). Part 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hinga, K.R.

Volume II of the sixth annual report describing the progress and evaluating the status of the Subseabed Disposal Program contains the appendices referred to in Volume I, Summary and Status. Because of the length of Volume II, it has been split into two parts for publication purposes. Part 1 contains Appendices A-Q; Part 2 contains Appendices R-MM. Separate abstracts have been prepared for each appendix for inclusion in the Energy Data Base.

Rasagiline: a review of its use in the treatment of idiopathic Parkinson's disease.

PubMed

Hoy, Sheridan M; Keating, Gillian M

2012-03-26

Rasagiline (Azilect®), a selective, irreversible, monoamine oxidase-B inhibitor, is available in the EU, the US and in several other countries worldwide, including Canada and Israel. It is indicated for the treatment of idiopathic Parkinson's disease as monotherapy or as adjunctive therapy to levodopa in patients [corrected]with end-of-dose fluctuations in the EU and for the treatment of adult patients with the signs and symptoms of idiopathic Parkinson's disease in the US. This article reviews the pharmacological properties, therapeutic efficacy and tolerability of rasagiline as monotherapy or as adjunctive therapy to levodopa in patients with Parkinson's disease. Oral rasagiline as monotherapy or as adjunctive therapy to levodopa was effective in the symptomatic treatment of adult patients with Parkinson's disease participating in double-blind, placebo-controlled, multinational studies. In patients with early Parkinson's disease, monotherapy with rasagiline 1 mg/day (recommended dosage) significantly slowed the rate of worsening (i.e. an increase in the Unified Parkinson's Disease Rating Scale [UPDRS] score) in the ADAGIO and TEMPO studies, with the results from the ADAGIO study for rasagiline 1 mg/day suggesting a slowing of clinical progression. However, at the higher dosage of 2 mg/day, rasagiline met the primary endpoint in the TEMPO study and the first, but not the second, of three hierarchical primary endpoints in the ADAGIO study. Compared with delayed-start rasagiline monotherapy, early initiation was associated with a slower long-term progression of the clinical signs and symptoms of Parkinson's disease in the TEMPO study. As adjunctive therapy to levodopa in the LARGO and PRESTO studies, rasagiline 0.5 and/or 1 mg/day significantly reduced the total daily 'off' time (primary efficacy endpoint) and significantly improved the Clinical Global Impression score, the UPDRS activities of daily living subscale score during 'off' time and the UPDRS motor subscale score during 'on' time compared with placebo in patients with advanced Parkinson's disease. Although rasagiline showed neuroprotective properties both in vitro and in vivo, identifying its potential to slow clinical progression in the clinical setting has been elusive to date and was not definitively demonstrated in the studies discussed in this article. Additional rasagiline studies specifically designed to assess the clinical progression of Parkinson's disease while addressing the potentially confounding factors of the delayed-start study design would therefore be of interest. As monotherapy or as adjunctive therapy to levodopa, rasagiline was generally well tolerated, with the frequency and nature of treatment-emergent adverse events generally similar across clinical studies and between rasagiline and placebo groups. Therapy with rasagiline appears to be associated with a low incidence of cognitive and behavioural adverse events. Thus, oral rasagiline as monotherapy or as adjunctive therapy to levodopa provides a useful option in the treatment of adult patients with Parkinson's disease.

Fourth - generation languages. Volume 2. Representative 4GLs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martin, J.

1986-01-01

The chapters in Part II each describe one representative product marketed by a vendor other than IBM. (Volume III of this work covers IBM languages.) The chapters in Part II cover the following 4GLs: ADS/ONLINE, APPLICATION FACTORY, DATATRIEVE, FOCUS, IDEAL, INTELLECT, MANTIS, MIMER, NATURAL, NOMAD2, RAMIS II, SYSTEM W, and USE-IT. The Perspective section of Part II presents a general overview of the product and describes its role in the marketplace. The Tutorial section describes how a user employs the language in application development.

Functional Ability Improved in Essential Tremor by IncobotulinumtoxinA Injections Using Kinematically Determined Biomechanical Patterns – A New Future

PubMed Central

Samotus, Olivia; Rahimi, Fariborz; Lee, Jack; Jog, Mandar

2016-01-01

Objective Effective treatment for functional disability caused by essential tremor is a significant unmet need faced by many clinicians today. Current literature regarding focal therapy by botulinum toxin type A (BoNT-A) injections uses fixed dosing regimens, which cannot be individualized, provides only limited functional benefit and unacceptable muscle weakness commonly occurs. This 38-week open label study, the longest to-date, demonstrates how kinematic technology addressed all these issues by guiding muscle selection. Method Participants (n = 24) were assessed at weeks 0, 6, 16, 22, 32, and 38 and injected with incobotulinumtoxinA at weeks 0, 16, and 32. Clinical assessments including UPDRS tremor items, Fahn-Tolosa-Marin (FTM) tremor rating scale assessing tremor severity, writing and functional ability, quality of life questionnaire (QUEST) and objective kinematic assessments were completed at every visit. Participants performed two postural and two weight-bearing scripted tasks with motion sensors placed over the wrist, elbow and shoulder joints. These sensors captured angular tremor amplitude (RMS units) and acceleration joint motion that was segmented into directional components: flexion-extension (F/E), pronation-supination and radial-ulnar at the wrist, F/E at the elbow, and F/E and adduction-abduction at the shoulder. Injection parameters were determined using kinematics, followed by the clinician’s determination of which muscles would contribute to the specific upper limb tremor biomechanics and dosing per participant. Results Multi-joint biomechanical recordings allowed individualized muscle selection and showed significant improvement in whole-arm function, FTM parts A-C scores, at week 6 which continued throughout the study. By week 38, the total FTM score statistically significantly reduced from 16.2±4.6 at week 0 to 9.5±6.3 (p<0.0005). UPDRS item 21 score rating action tremor was significantly reduced from 2.6±0.5 at week 0 to 1.6±1.1 (p = 0.01) at week 32. Quality of life (QUEST) significantly improved from 40.3±15.8 at week 0 to 31.1±15.3 (p = 0.035) at week 32 and to 27.8±15.3 (p = 0.028) at week 38. Kinematics provided an objective, secondary outcome measure, which showed a significant decrease in tremor amplitude in the wrist and shoulder joints (p<0.05). Eight participants (40%) self-reported mild weakness in injected muscles but had no interference in arm function. Conclusion Kinematic tremor assessments provide the injector unique insight to objectively individualize and personalize injection parameters demonstrating BoNT-A effectively alleviates functional disability caused by essential tremor. Kinematic technology is a promising method for standardizing assessments and for focal upper limb tremor treatment. Trial Registration ClinicalTrials.gov NCT02427646 PMID:27101283

40 CFR Appendix II to Part 1042 - Steady-State Duty Cycles

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 32 2010-07-01 2010-07-01 false Steady-State Duty Cycles II Appendix..., App. II Appendix II to Part 1042—Steady-State Duty Cycles (a) The following duty cycles apply as specified in § 1042.505(b)(1): (1) The following duty cycle applies for discrete-mode testing: E3 mode No...

40 CFR Table 2 to Subpart II of... - Volatile Organic HAP (VOHAP) Limits for Marine Coatings

Code of Federal Regulations, 2013 CFR

2013-07-01

... for Marine Coatings 2 Table 2 to Subpart II of Part 63 Protection of Environment ENVIRONMENTAL... (Surface Coating) Pt. 63, Subpt. II, Table 2 Table 2 to Subpart II of Part 63—Volatile Organic HAP (VOHAP) Limits for Marine Coatings Coating category VOHAP limits a,b,c Grams/liter coating (minus water and...

40 CFR Table 2 to Subpart II of... - Volatile Organic HAP (VOHAP) Limits for Marine Coatings

Code of Federal Regulations, 2012 CFR

2012-07-01

... for Marine Coatings 2 Table 2 to Subpart II of Part 63 Protection of Environment ENVIRONMENTAL... (Surface Coating) Pt. 63, Subpt. II, Table 2 Table 2 to Subpart II of Part 63—Volatile Organic HAP (VOHAP) Limits for Marine Coatings Coating category VOHAP limits a,b,c Grams/liter coating (minus water and...

40 CFR Table 2 to Subpart II of... - Volatile Organic HAP (VOHAP) Limits for Marine Coatings

Code of Federal Regulations, 2014 CFR

2014-07-01

... for Marine Coatings 2 Table 2 to Subpart II of Part 63 Protection of Environment ENVIRONMENTAL... (Surface Coating) Pt. 63, Subpt. II, Table 2 Table 2 to Subpart II of Part 63—Volatile Organic HAP (VOHAP) Limits for Marine Coatings Coating category VOHAP limits a b c Grams/liter coating (minus water and...

40 CFR Table 2 to Subpart II of... - Volatile Organic HAP (VOHAP) Limits for Marine Coatings

Code of Federal Regulations, 2010 CFR

2010-07-01

... for Marine Coatings 2 Table 2 to Subpart II of Part 63 Protection of Environment ENVIRONMENTAL... (Surface Coating) Pt. 63, Subpt. II, Table 2 Table 2 to Subpart II of Part 63—Volatile Organic HAP (VOHAP) Limits for Marine Coatings Coating category VOHAP limits a,b,c Grams/liter coating (minus water and...

40 CFR Table 2 to Subpart II of... - Volatile Organic HAP (VOHAP) Limits for Marine Coatings

Code of Federal Regulations, 2011 CFR

2011-07-01

... for Marine Coatings 2 Table 2 to Subpart II of Part 63 Protection of Environment ENVIRONMENTAL... (Surface Coating) Pt. 63, Subpt. II, Table 2 Table 2 to Subpart II of Part 63—Volatile Organic HAP (VOHAP) Limits for Marine Coatings Coating category VOHAP limits a,b,c Grams/liter coating (minus water and...

The associations between fatigue, apathy, and depression in Parkinson's disease.

PubMed

Skorvanek, M; Gdovinova, Z; Rosenberger, J; Saeedian, R Ghorbani; Nagyova, I; Groothoff, J W; van Dijk, J P

2015-02-01

Fatigue and apathy are two of the most common and most disabling non-motor symptoms of Parkinson's disease (PD). They have a high coincidence and can often be confused; moreover, their relationship is not fully understood. The aim of our study was to describe the coincidence of apathy with different fatigue domains in the presence/absence of depression and to separately describe the associations of different aspects of primary and secondary fatigue with apathy and other clinical and disease-related factors. A total of 151 non-demented patients with PD were examined using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Starkstein Apathy Scale, Multidimensional Fatigue Inventory (MFI), Beck Depression Inventory-II, and Epworth Sleepiness Scale. The prevalence and severity of fatigue and apathy were significantly higher in depressed PD patients. However, our results show that depression, fatigue, and apathy can be clearly distinguished in PD. Apathy was associated with the MFI's-reduced motivation domain in both depressed and non-depressed patients. However, apathy was associated with mental fatigue aspects only in non-depressed patients, and it was not related to the physical aspects of fatigue in any of the studied groups. Although the pathophysiology of fatigue and apathy in PD is clearly multifactorial, in a proportion of PD patients, these symptoms are associated with depression, dopaminergic depletion in the mesocorticolimbic structures, and disruption of the prefrontal cortex-basal ganglia axis. Therefore, in some PD patients, adequate management of depression and optimal dopaminergic medication may improve both fatigue and apathy. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

31 CFR Appendix II to Part 13 - Form of Bill for Reimbursement

Code of Federal Regulations, 2010 CFR

2010-07-01

... title) of ______ (Country) to participate in the work of ______ (International Organization) or occurring at the _______ (Permanent or observer mission) to ______ (International organization) during the.... II Appendix II to Part 13—Form of Bill for Reimbursement I hereby request that ______ (Governmental...

Effects of soybean ingestion on pharmacokinetics of levodopa and motor symptoms of Parkinson's disease--In relation to the effects of Mucuna pruriens.

PubMed

Nagashima, Yasuhiro; Kondo, Tomoyoshi; Sakata, Mayumi; Koh, Jinsoo; Ito, Hidefumi

2016-02-15

Mucuna pruriens is a levodopa-containing legume and its favorable effects on motor complications in Parkinson disease patients have been reported. The aim of this study was to investigate the effects of another legume, soybeans, on the pharmacokinetics and metabolism of levodopa. Seven parkinsonian patients with the wearing-off phenomenon and dyskinesia and five healthy volunteers participated in this study. We conducted a crossover study of the clinical effects on the participants before and after taking either levodopa (100mg)/carbidopa (10mg) only (LD/CD) or levodopa/carbidopa with 11 g of ground soybeans (LD/CD/soy). Parkinsonism and dyskinesia before and after ingestion of these substances were evaluated using UPDRS part III, the modified Abnormal Involuntary Movement Scale (mAIMS) and a self-rating scale. The concentrations of plasma levodopa and its major metabolites were measured by high-performance liquid chromatography. Clinical assessment and blood sampling were conducted before and three hours after the ingestion of ground soybeans. When the patients took LD/CD/soy, they had a significantly longer on-period (p=0.028) and a lower mAIMS score (p<0.001). From the comparison of the results of pharmacokinetic study before and after taking LD/CD or LD/CD/soy, the estimated marginal mean (EMM) of HVA after LD/CD/soy increased in the PD group. EMMs of 3-OMD after LD/CD/soy significantly decreased both in PD patients and healthy controls. These results indicate that soy partly increased the bioavailability of levodopa and suppressed levodopa degradation through COMT. Soybeans may have favorable effects on the motor complications occurring under current levodopa therapy. Further investigation to clarify the mechanism underlying such effects is required. Copyright © 2015 Elsevier B.V. All rights reserved.

Association Between National Board Dental Examination Part II Scores and Comprehensive Examinations at Harvard School of Dental Medicine.

PubMed

Lee, Min Kyeong; Allareddy, Veerasathpurush; Howell, T Howard; Karimbux, Nadeem Y

2011-01-01

Harvard School of Dental Medicine (HSDM) uses a hybrid problem-based approach to teaching in the predoctoral program. The objective structured clinical examination (OSCE) is a formative examination designed to assess the performance of students in the problem-based learning (PBL) curriculum. At HSDM three comprehensive examinations with OSCE components are administered during the third and fourth years of clinical training. The National Board Dental Examination (NBDE) Part II is taken in the final year of the predoctoral program. This study examines the association between the NBDE Part II and the comprehensive exams held at HSDM. Predoctoral students from the HSDM classes of 2005 and 2006 were included in this study. The outcome variable of interest was the scores obtained by students in the NBDE Part II, and the main independent variable of interest was the performance of students in the comprehensive exams (honors, pass, make-up exam to pass). The Mann-Whitney U-test was used to examine the association between the grades obtained in the each of the three comprehensive exams and the NBDE Part II scores. Multivariable linear regression analysis was also used to examine the association between the NBDE Part II scores and the comprehensive exam grades. The effect of potential confounding factors including age, sex, and race/ethnicity was adjusted. The results suggest that students who performed well in the comprehensive exams performed better on the NBDE Part II, even after adjusting for confounding factors. Future studies will examine the long-term impact of PBL on postdoctoral plans and career choices.

A Study of Mandarin Loanwords: Lexical Stratification, Adaptation and Factors

ERIC Educational Resources Information Center

Kim, Tae Eun

2012-01-01

This dissertation is about Chinese loanwords. It is mainly divided into two parts. Part I is a general discussion about loanwords in Chinese; Chapter I and II belong to the first part. Part II is a discussion about the analyses of Mandarin loanwords originating from English. Chapter III, IV, and V are all related to the second part. Chapter VI is…

Network Centric Operations (NCO) Case Study. The British Approach to Low-Intensity Operations: Part 2

DTIC Science & Technology

2007-02-12

Imperial War Museum Sound Archive, Accession No. 16397 (6 January 1996 ) 46 Jackson, p .45 47 Nagl, p .66-7 48 Stubbs, p .71 49 Nagl, p .93 Part II 16...Coogan, The Troubles, (London: Arrow, 1996 ), p .145 Part II 61 of 246 but there really appeared to be nothing in between to provide workable...Psychological Ops Capability Since 1945’, British Army Review, December 1996 , p .5 Part II 62 of 246 weakness caused by the lack of both numbers and

20 CFR 408.101 - What is this part about?

Code of Federal Regulations, 2011 CFR

2011-04-01

....101 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II... (Special Benefits for Certain World War II Veterans) established a program for the payment of benefits to certain World War II veterans. The regulations in this part are divided into the following subparts...

20 CFR 408.101 - What is this part about?

Code of Federal Regulations, 2014 CFR

2014-04-01

....101 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II... (Special Benefits for Certain World War II Veterans) established a program for the payment of benefits to certain World War II veterans. The regulations in this part are divided into the following subparts...

20 CFR 408.101 - What is this part about?

Code of Federal Regulations, 2013 CFR

2013-04-01

....101 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II... (Special Benefits for Certain World War II Veterans) established a program for the payment of benefits to certain World War II veterans. The regulations in this part are divided into the following subparts...

20 CFR 408.101 - What is this part about?

Code of Federal Regulations, 2012 CFR

2012-04-01

....101 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II... (Special Benefits for Certain World War II Veterans) established a program for the payment of benefits to certain World War II veterans. The regulations in this part are divided into the following subparts...

Verbal Memory Decline following DBS for Parkinson's Disease: Structural Volumetric MRI Relationships.

PubMed

Geevarghese, Ruben; Lumsden, Daniel E; Costello, Angela; Hulse, Natasha; Ayis, Salma; Samuel, Michael; Ashkan, Keyoumars

2016-01-01

Parkinson's disease is a chronic degenerative movement disorder. The mainstay of treatment is medical. In certain patients Deep Brain Stimulation (DBS) may be offered. However, DBS has been associated with post-operative neuropsychology changes, especially in verbal memory. Firstly, to determine if pre-surgical thalamic and hippocampal volumes were related to verbal memory changes following DBS. Secondly, to determine if clinical factors such as age, duration of symptoms or motor severity (UPDRS Part III score) were related to verbal memory changes. A consecutive group of 40 patients undergoing bilateral Subthalamic Nucleus (STN)-DBS for PD were selected. Brain MRI data was acquired, pre-processed and structural volumetric data was extracted using FSL. Verbal memory test scores for pre- and post-STN-DBS surgery were recorded. Linear regression was used to investigate the relationship between score change and structural volumetric data. A significant relationship was demonstrated between change in List Learning test score and thalamic (left, p = 0.02) and hippocampal (left, p = 0.02 and right p = 0.03) volumes. Duration of symptoms was also associated with List Learning score change (p = 0.02 to 0.03). Verbal memory score changes appear to have a relationship to pre-surgical MRI structural volumetric data. The findings of this study provide a basis for further research into the use of pre-surgical MRI to counsel PD patients regarding post-surgical verbal memory changes.

Global Mobility Task: index for evaluating motor impairment and motor rehabilitation programs in Parkinson's disease patients.

PubMed

Peppe, A; Ranaldi, A; Chiavalon, C; Gasbarra, A; Collepardo, A; Romeo, R; Pasqualetti, P; Caltagirone, C

2007-09-01

In this study, the validity of a motor task, i.e., the Global Mobility Task (GMT), was assessed in a group of Parkinson's disease (PD) patients. Fifty-eight PD patients (mean age: 68.7 years) and 18 healthy subjects (mean age: 65.8 years) were enrolled in the study. The GMT measures the ability of an adult to roll over on the floor and stand up in five steps using two parameters: 'Time' and 'Score', i.e., the time needed and the ability to perform each step of the task. As the GMT has never been evaluated before, internal consistency and concurrent and discriminative validity were considered in assessing its characteristics in a group of PD patients at the beginning and at the end of a motor rehabilitation program. To determine whether the GMT could also quantify the extrapyramidal impairment, we compared data collected using this task with data obtained using clinical scales such as the Unified Parkinson's Disease Rating Scale III (UPDRS part III) and Hoehn & Yahr's score. Results showed that the GMT had good consistency and inter-rater reproducibility, was closely related to clinical scales and was able to detect the amelioration of extrapyramidal symptoms at the end of the motor rehabilitation program. we propose the GMT as a tool for measuring impaired mobility in PD patients and for evaluating the objective effects of motor rehabilitation programs.

12 CFR Appendix II to Part 27 - Information for Government Monitoring Purposes

Code of Federal Regulations, 2010 CFR

2010-01-01

... II Appendix II to Part 27 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY... Monitoring Purposes The following language is approved by the Comptroller of the Currency and will satisfy... used separately. This information may also be provided orally by the applicant. The following...

40 CFR Appendix II to Part 86 - Temperature Schedules

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 19 2014-07-01 2014-07-01 false Temperature Schedules II Appendix II... to Part 86—Temperature Schedules (a) Ambient temperature cycle for the diurnal emission portion of the evaporative emission test (see § 86.133). Table I—Temperature Versus Time Sequence Use linear...

25 CFR 547.1 - What is the purpose of this part?

Code of Federal Regulations, 2011 CFR

2011-04-01

... STANDARDS FOR GAMING EQUIPMENT USED WITH THE PLAY OF CLASS II GAMES § 547.1 What is the purpose of this part... other technologic aids in connection with the play of Class II games. This part establishes the minimum...

25 CFR 547.1 - What is the purpose of this part?

Code of Federal Regulations, 2010 CFR

2010-04-01

... STANDARDS FOR GAMING EQUIPMENT USED WITH THE PLAY OF CLASS II GAMES § 547.1 What is the purpose of this part... other technologic aids in connection with the play of Class II games. This part establishes the minimum...

25 CFR 547.1 - What is the purpose of this part?

Code of Federal Regulations, 2012 CFR

2012-04-01

... STANDARDS FOR GAMING EQUIPMENT USED WITH THE PLAY OF CLASS II GAMES § 547.1 What is the purpose of this part... other technologic aids in connection with the play of Class II games. This part establishes the minimum...

Some biodiversity points and suggestions for the Myanmar Protected Area System

Treesearch

Daniel H. Henning

2007-01-01

This paper is divided into a brief background section followed by Part I: Biodiversity Points, and Part II: Suggestions that are needed for the ecological integrity of actual and potential protected areas in Myanmar. Part I consists of general and Myanmar Biodiversity Considerations, and Part II consists of the following suggestions: (l) international financial and...

Understanding Medicines: Conceptual Analysis of Nurses' Needs for Knowledge and Understanding of Pharmacology (Part I). Understanding Medicines: Extending Pharmacology Education for Dependent and Independent Prescribing (Part II).

ERIC Educational Resources Information Center

Leathard, Helen L.

2001-01-01

Part I reviews what nurses need to know about the administration and prescription of medicines. Part II addresses drug classifications, actions and effects, and interactions. Also discussed are the challenges pharmacological issues pose for nursing education. (SK)

Estimating Welfare Effects Consistent with Forward-Looking Behavior. Part I: Lessons from a Simulation Exercise. Part II: Empirical Results.

ERIC Educational Resources Information Center

Keane, Michael P.; Wolpin, Kenneth I.

2002-01-01

Part I uses simulations of a model of welfare participation and women's fertility decisions, showing that increases in per-child payments have substantial impact on fertility. Part II uses estimations of decision rules of forward-looking women regarding welfare participation, fertility, marriage, work, and schooling. (SK)

Multiple regression analysis to assess the role of plankton on the distribution and speciation of mercury in water of a contaminated lagoon.

PubMed

Stoichev, T; Tessier, E; Amouroux, D; Almeida, C M; Basto, M C P; Vasconcelos, V M

2016-11-15

Spatial and seasonal variation of mercury species aqueous concentrations and distributions was carried out during six sampling campaigns at four locations within Laranjo Bay, the most mercury-contaminated area of the Aveiro Lagoon (Portugal). Inorganic mercury (IHg(II)) and methylmercury (MeHg) were determined in filter-retained (IHgPART, MeHgPART) and filtered (<0.45μm) fractions (IHg(II)DISS, MeHgDISS). The concentrations of IHgPART depended on site and on dilution with downstream particles. Similar processes were evidenced for MeHgPART, however, its concentrations increased for particles rich in phaeophytin (Pha). The concentrations of MeHgDISS, and especially those of IHg(II)DISS, increased with Pha concentrations in the water. Multiple regression models are able to depict MeHgPART, IHg(II)DISS and MeHgDISS concentrations with salinity and Pha concentrations exhibiting additive statistical effects and allowing separation of possible addition and removal processes. A link between phytoplankton/algae and consumers' grazing pressure in the contaminated area can be involved to increase concentrations of IHg(II)DISS and MeHgPART. These processes could lead to suspended particles enriched with MeHg and to the enhancement of IHg(II) and MeHg availability in surface waters and higher transfer to the food web. Copyright © 2016 Elsevier B.V. All rights reserved.

40 CFR Appendix II to Part 1045 - Duty Cycles for Propulsion Marine Engines

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 33 2011-07-01 2011-07-01 false Duty Cycles for Propulsion Marine...) AIR POLLUTION CONTROLS CONTROL OF EMISSIONS FROM SPARK-IGNITION PROPULSION MARINE ENGINES AND VESSELS Pt. 1045, App. II Appendix II to Part 1045—Duty Cycles for Propulsion Marine Engines (a) The...

40 CFR Appendix II to Part 1045 - Duty Cycles for Propulsion Marine Engines

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 33 2014-07-01 2014-07-01 false Duty Cycles for Propulsion Marine...) AIR POLLUTION CONTROLS CONTROL OF EMISSIONS FROM SPARK-IGNITION PROPULSION MARINE ENGINES AND VESSELS Pt. 1045, App. II Appendix II to Part 1045—Duty Cycles for Propulsion Marine Engines (a) The...

40 CFR Appendix II to Part 1045 - Duty Cycles for Propulsion Marine Engines

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 34 2013-07-01 2013-07-01 false Duty Cycles for Propulsion Marine...) AIR POLLUTION CONTROLS CONTROL OF EMISSIONS FROM SPARK-IGNITION PROPULSION MARINE ENGINES AND VESSELS Pt. 1045, App. II Appendix II to Part 1045—Duty Cycles for Propulsion Marine Engines (a) The...

40 CFR Appendix II to Part 1045 - Duty Cycles for Propulsion Marine Engines

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 34 2012-07-01 2012-07-01 false Duty Cycles for Propulsion Marine...) AIR POLLUTION CONTROLS CONTROL OF EMISSIONS FROM SPARK-IGNITION PROPULSION MARINE ENGINES AND VESSELS Pt. 1045, App. II Appendix II to Part 1045—Duty Cycles for Propulsion Marine Engines (a) The...

Dissecting Diversity Part II

ERIC Educational Resources Information Center

Matthews, Frank

2005-01-01

This article presents "Dissecting Diversity, Part II," the conclusion of a wide-ranging two-part roundtable discussion on diversity in higher education. The participants were as follows: Lezli Baskerville, J.D., President and CEO of the National Association for Equal Opportunity (NAFEO); Dr. Gerald E. Gipp, Executive Director of the…

Recent Economic Perspectives on Political Economy, Part II*

PubMed Central

Dewan, Torun; Shepsle, Kenneth A.

2013-01-01

In recent years some of the best theoretical work on the political economy of political institutions and processes has begun surfacing outside the political science mainstream in high quality economics journals. This two-part paper surveys these contributions from a recent five-year period. In Part I, the focus is on elections, voting and information aggregation, followed by treatments of parties, candidates, and coalitions. In Part II, papers on economic performance and redistribution, constitutional design, and incentives, institutions, and the quality of political elites are discussed. Part II concludes with a discussion of the methodological bases common to economics and political science, the way economists have used political science research, and some new themes and arbitrage opportunities. PMID:23606754

40 CFR Appendix B to Subpart II of... - Maximum Allowable Thinning Rates as a Function of As Supplied VOC Content and Thinner Density

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 11 2013-07-01 2013-07-01 false Maximum Allowable Thinning Rates as a Function of As Supplied VOC Content and Thinner Density B Appendix B to Subpart II of Part 63 Protection of... Shipbuilding and Ship Repair (Surface Coating) Pt. 63, Subpt. II, App. B Appendix B to Subpart II of Part 63...

40 CFR Appendix B to Subpart II to... - Maximum Allowable Thinning Rates as a Function of As Supplied VOC Content and Thinner Density

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 10 2011-07-01 2011-07-01 false Maximum Allowable Thinning Rates as a Function of As Supplied VOC Content and Thinner Density B Appendix B to Subpart II to Part 63 Protection of... Shipbuilding and Ship Repair (Surface Coating) Pt. 63, Subpt. II, App. B Appendix B to Subpart II to Part 63...

Chimeric Lyssavirus Glycoproteins with Increased Immunological Potential

PubMed Central

Jallet, Corinne; Jacob, Yves; Bahloul, Chokri; Drings, Astrid; Desmezieres, Emmanuel; Tordo, Noël; Perrin, Pierre

1999-01-01

The rabies virus glycoprotein molecule (G) can be divided into two parts separated by a flexible hinge: the NH2 half (site II part) containing antigenic site II up to the linear region (amino acids [aa] 253 to 275 encompassing epitope VI [aa 264]) and the COOH half (site III part) containing antigenic site III and the transmembrane and cytoplasmic domains. The structural and immunological roles of each part were investigated by cell transfection and mouse DNA-based immunization with homogeneous and chimeric G genes formed by fusion of the site II part of one genotype (GT) with the site III part of the same or another GT. Various site II-site III combinations between G genes of PV (Pasteur virus strain) rabies (GT1), Mokola (GT3), and EBL1 (European bat lyssavirus 1 [GT5]) viruses were tested. Plasmids pGPV-PV, pGMok-Mok, pGMok-PV, and pGEBL1-PV induced transient expression of correctly transported and folded antigens in neuroblastoma cells and virus-neutralizing antibodies against parental viruses in mice, whereas, pG-PVIII (site III part only) and pGPV-Mok did not. The site III part of PV (GT1) was a strong inducer of T helper cells and was very effective at presenting the site II part of various GTs. Both parts are required for correct folding and transport of chimeric G proteins which have a strong potential value for immunological studies and development of multivalent vaccines. Chimeric plasmid pGEBL1-PV broadens the spectrum of protection against European lyssavirus genotypes (GT1, GT5, and GT6). PMID:9847325

Unlearning Established Organizational Routines--Part II

ERIC Educational Resources Information Center

Fiol, C. Marlena; O'Connor, Edward J.

2017-01-01

Purpose: The purpose of Part II of this two-part paper is to uncover important differences in the nature of the three unlearning subprocesses, which call for different leadership interventions to motivate people to move through them. Design/methodology/approach: The paper draws on research in behavioral medicine and psychology to demonstrate that…

Aquatic therapy versus conventional land-based therapy for Parkinson's disease: an open-label pilot study.

PubMed

Vivas, Jamile; Arias, Pablo; Cudeiro, Javier

2011-08-01

To assess and compare 2 different protocols of physiotherapy (land or water therapy) for people with Parkinson's disease (PD) focused on postural stability and self-movement, and to provide methodological information regarding progression within the program for a future larger trial. Randomized, controlled, open-label pilot trial. Outpatients, Parkinson's disease Center of Ferrol-Galicia (Spain). Individuals (N=11) with idiopathic PD in stages 2 or 3 according to the Hoehn and Yahr Scale completed the investigation (intervention period plus follow-up). After baseline evaluations, participants were randomly assigned to a land-based therapy (active control group) or a water-based therapy (experimental group). Participants underwent individual sessions for 4 weeks, twice a week, for 45 minutes per session. Both interventions were matched in terms of exercise features, which were structured in stages with clear objectives and progression criteria to pass to the next phase. Participants underwent a first baseline assessment, a posttest immediately after 4 weeks of intervention, and a follow-up assessment after 17 days. Evaluations were performed OFF-dose after withholding medication for 12 hours. Functional assessments included the Functional Reach Test (FRT), the Berg Balance Scale (BBS), the UPDRS, the 5-m walk test, and the Timed Up and Go test. A main effect of both therapies was seen for the FRT. Only the aquatic therapy group improved in the BBS and the UPDRS. In this pilot study, physiotherapy protocols produced improvement in postural stability in PD that was significantly larger after aquatic therapy. The intervention protocols are shown to be feasible and seem to be of value in amelioration of postural stability-related impairments in PD. Some of the methodological aspects detailed here can be used to design larger controlled trials. Copyright © 2011 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Deep Brain Stimulation for Parkinson's Disease with Early Motor Complications: A UK Cost-Effectiveness Analysis.

PubMed

Fundament, Tomasz; Eldridge, Paul R; Green, Alexander L; Whone, Alan L; Taylor, Rod S; Williams, Adrian C; Schuepbach, W M Michael

2016-01-01

Parkinson's disease (PD) is a debilitating illness associated with considerable impairment of quality of life and substantial costs to health care systems. Deep brain stimulation (DBS) is an established surgical treatment option for some patients with advanced PD. The EARLYSTIM trial has recently demonstrated its clinical benefit also in patients with early motor complications. We sought to evaluate the cost-effectiveness of DBS, compared to best medical therapy (BMT), among PD patients with early onset of motor complications, from a United Kingdom (UK) payer perspective. We developed a Markov model to represent the progression of PD as rated using the Unified Parkinson's Disease Rating Scale (UPDRS) over time in patients with early PD. Evidence sources were a systematic review of clinical evidence; data from the EARLYSTIM study; and a UK Clinical Practice Research Datalink (CPRD) dataset including DBS patients. A mapping algorithm was developed to generate utility values based on UPDRS data for each intervention. The cost-effectiveness was expressed as the incremental cost per quality-adjusted life-year (QALY). One-way and probabilistic sensitivity analyses were undertaken to explore the effect of parameter uncertainty. Over a 15-year time horizon, DBS was predicted to lead to additional mean cost per patient of £26,799 compared with BMT (£73,077/patient versus £46,278/patient) and an additional mean 1.35 QALYs (6.69 QALYs versus 5.35 QALYs), resulting in an incremental cost-effectiveness ratio of £19,887 per QALY gained with a 99% probability of DBS being cost-effective at a threshold of £30,000/QALY. One-way sensitivity analyses suggested that the results were not significantly impacted by plausible changes in the input parameter values. These results indicate that DBS is a cost-effective intervention in PD patients with early motor complications when compared with existing interventions, offering additional health benefits at acceptable incremental cost. This supports the extended use of DBS among patients with early onset of motor complications.

Using R in experimental design with BIBD: An application in health sciences

NASA Astrophysics Data System (ADS)

Oliveira, Teresa A.; Francisco, Carla; Oliveira, Amílcar; Ferreira, Agostinho

2016-06-01

Considering the implementation of an Experimental Design, in any field, the experimenter must pay particular attention and look for the best strategies in the following steps: planning the design selection, conduct the experiments, collect observed data, proceed to analysis and interpretation of results. The focus is on providing both - a deep understanding of the problem under research and a powerful experimental process at a reduced cost. Mainly thanks to the possibility of allowing to separate variation sources, the importance of Experimental Design in Health Sciences is strongly recommended since long time. Particular attention has been devoted to Block Designs and more precisely to Balanced Incomplete Block Designs - in this case the relevance states from the fact that these designs allow testing simultaneously a number of treatments bigger than the block size. Our example refers to a possible study of inter reliability of the Parkinson disease, taking into account the UPDRS (Unified Parkinson's disease rating scale) in order to test if there are significant differences between the specialists who evaluate the patients performances. Statistical studies on this disease were described for example in Richards et al (1994), where the authors investigate the inter-rater Reliability of the Unified Parkinson's Disease Rating Scale Motor Examination. We consider a simulation of a practical situation in which the patients were observed by different specialists and the UPDRS on assessing the impact of Parkinson's disease in patients was observed. Assigning treatments to the subjects following a particular BIBD(9,24,8,3,2) structure, we illustrate that BIB Designs can be used as a powerful tool to solve emerging problems in this area. Once a structure with repeated blocks allows to have some block contrasts with minimum variance, see Oliveira et al. (2006), the design with cardinality 12 was selected for the example. R software was used for computations.

Validation of the Bulgarian version of Scales for Outcomes in Parkinson's Disease - Autonomic (SCOPA-AUT-BG).

PubMed

Mantarova, Stefka G; Velcheva, Irena V; Georgieva, Spaska O; Stambolieva, Katerina I

2013-01-01

The last twenty years have witnessed a surge of interest in the autonomic symptoms in Parkinson's disease (PD) and the possibilities to diagnose and treat them. The specialized questionnaire assessing the autonomic symptoms in Parkinson's disease (SCOPA-AUT) has been validated and available in English, Dutch and Spanish. In this study we aim at evaluating the validity, reliability and applicability of the Bulgarian version of SCOPA-AUT (SCOPA-AUT-BG). The study included 55 patients with idiopathic PD (mean age 64.4 +/- 8.9 yrs), and 40 healthy controls (mean age 58.5 +/- 9.4 yrs). Clinical severity and disease stage were assessed by United Parkinson's disease rating scale (UPRDS) and Hoen and Yahr (H&Y). Thirty-two of the PD patients completed SCOPA-AUT-BG again after a 7-day interval. Questionnaire reliability was analyzed by determining the internal consistency, homogeneity, discriminatory and construct validity and test-retest reliability. Analyses showed good internal consistency of the summary evaluation of SCOPA-AUT-BG (coefficient alpha of Cronbach = 0.79), which indicates the high reliability of the questionnaire. The lowest Cronbach's alpha coefficient (0.53) was found for the subscale "cardiovascular functions". A dominant role belongs to the subscales for gastrointestinal and urinary functions (Cronbach's Alpha > 0.7), where a significantly high correlation of PD with the UPDRS scale was observed. We found high test-retest reliability based on the responses associated with dysfunction of the gastrointestinal, urinary, thermoregulatory and pupillary autonomic systems. The correlation of the results of SCOPA-AUT-BG with UPDRS is higher than that with H&Y, and the construct validity is high except for the cardiovascular and pupillomotor functions subscales. The results of this study show that SCOPA-AUT-BG is a valid and reliable specialized questionnaire to evaluate autonomic function in patients with Parkinson's disease. Using it allows for more detailed clinical evaluation of these patients and justifies the need to refer them to specialized examination of autonomic functions.

Verification of a Method for Measuring Parkinson's Disease Related Temporal Irregularity in Spiral Drawings.

PubMed

Aghanavesi, Somayeh; Memedi, Mevludin; Dougherty, Mark; Nyholm, Dag; Westin, Jerker

2017-10-13

Parkinson's disease (PD) is a progressive movement disorder caused by the death of dopamine-producing cells in the midbrain. There is a need for frequent symptom assessment, since the treatment needs to be individualized as the disease progresses. The aim of this paper was to verify and further investigate the clinimetric properties of an entropy-based method for measuring PD-related upper limb temporal irregularities during spiral drawing tasks. More specifically, properties of a temporal irregularity score (TIS) for patients at different stages of PD, and medication time points were investigated. Nineteen PD patients and 22 healthy controls performed repeated spiral drawing tasks on a smartphone. Patients performed the tests before a single levodopa dose and at specific time intervals after the dose was given. Three movement disorder specialists rated videos of the patients based on the unified PD rating scale (UPDRS) and the Dyskinesia scale. Differences in mean TIS between the groups of patients and healthy subjects were assessed. Test-retest reliability of the TIS was measured. The ability of TIS to detect changes from baseline (before medication) to later time points was investigated. Correlations between TIS and clinical rating scores were assessed. The mean TIS was significantly different between healthy subjects and patients in advanced groups ( p -value = 0.02). Test-retest reliability of TIS was good with Intra-class Correlation Coefficient of 0.81. When assessing changes in relation to treatment, TIS contained some information to capture changes from Off to On and wearing off effects. However, the correlations between TIS and clinical scores (UPDRS and Dyskinesia) were weak. TIS was able to differentiate spiral drawings drawn by patients in an advanced stage from those drawn by healthy subjects, and TIS had good test-retest reliability. TIS was somewhat responsive to single-dose levodopa treatment. Since TIS is an upper limb high-frequency-based measure, it cannot be detected during clinical assessment.

A single-blind cross over study investigating the efficacy of standard and controlled release levodopa in combination with entacapone in the treatment of end-of-dose effect in people with Parkinson's disease.

PubMed

Iansek, R; Danoudis, M

2011-08-01

To determine the efficacy of standard levodopa combined with controlled release levodopa and entacapone in controlling end-of-dose symptoms in Parkinson's disease. A single-blind cross over design was used to compare the duration of action for three pharmacological combinations: standard levodopa (L/DDC); standard levodopa combined with entacapone (L/DDC/E); and standard levodopa combined with controlled release levodopa (CR) and entacapone (L/DDC/CR/E). Thirty two participants with wearing-off symptoms and inadequate symptom control with L/DDC/E had their optimum dose of L/DDC determined at base line. Entacapone was added to the optimal L/DDC dose and duration of action determined. Levodopa CR dosage was adjusted to match the optimal L/DDC dose for each participant. All participants were then trialed on L/DDC/CR/E and duration of response calculated. Timed Up and Go (TUG) times and magnitude of extra movements were recorded hourly throughout the day over several days to determine the optimum interval between doses for each combination. The UPDRS (Sections 2 and 3), PDQ39 and fatigue scale, the PDF-16, were recorded at base line and when dosage intervals had stabilized on L/DDC/CR/E. Duration of response was greatest with L/DDC/CR/E compared to L/DDC/E (p < 0.001) and number of daily doses were less on L/DDC/CR/E compared to L/DDC/E (p < 0.001). UPDRS, PDQ39 and fatigue scores also improved on L/DDC/CR/E compared to L/DDC (p < 0.001). Dyskinesia increased on L/DDC/CR/E (p = 0.001) however magnitude was mild. Combining standard levodopa and levodopa CR preparations with entacapone is an additional treatment strategy to manage motor fluctuations in advanced PD. Copyright © 2011 Elsevier Ltd. All rights reserved.

Inhibitory motor dysfunction in parkinson's disease subtypes.

PubMed

Gong, Tao; Xiang, Yuanyuan; Saleh, Muhammad G; Gao, Fei; Chen, Weibo; Edden, Richard A E; Wang, Guangbin

2018-06-01

Parkinson's disease (PD) is divided into postural instability gait difficulty (PIGD) and tremor-dominant (TD) subtypes. Increasing evidence has suggested that the GABAergic neurotransmitter system is involved in the pathogenesis of PD. To evaluate the differences of GABA levels between PD motor subtypes using MEscher-GArwood Point Resolved Spectroscopy (MEGA-PRESS). COHORT.: SUBJECTS: PD patients were classified into PIGD (n = 13) and TD groups (n = 9); 16 age- and sex-matched healthy controls were also recruited. All subjects were right-handed. All subjects underwent an magnetic resonance spectroscopy scan including MEGA-PRESS at 3.0T. The detected GABA signal also contains signal from macromolecules (MM) and homocarnosine, so it is referred to as GABA+. GABA + levels and Creatine (Cr) levels were quantified in the left basal ganglia (BG) using Gannet 2.0 by Tao Gong. Differences in GABA + levels between the three groups were analyzed using analysis of covariance. The relationship between GABA levels and a unified PD rating scale (UPDRS) was also analyzed. GABA + levels were significantly lower in left BG regions of PD patients compared with healthy controls (P < 0.001). In PD patients, the GABA concentration was lower in the TD group than the PIGD group (P = 0.019). Cr levels in PIGD and TD were lower than controls (P = 0.020; P = 0.002). A significant negative correlation was found in PIGD between GABA levels and UPDRS (r = -0.572, P = 0.041), while no correlation was found in TD (r = -0.339, P = 0.372). Low BG GABA levels in PD patients, and differences between PIGD/TD patients, suggest that GABAergic dysfunction may play an important role in the pathogenesis of Parkinson's disease. 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1610-1615. © 2017 International Society for Magnetic Resonance in Medicine.

Assessment of postural control in patients with Parkinson's disease: sway ratio analysis.

PubMed

Błaszczyk, Janusz W; Orawiec, Renata

2011-04-01

Analysis of the postural stability impairments in neurodegenerative diseases is a very demanding task. Age-related declines in posturographic indices are usually superimposed on effects associated with the pathology and its treatment. We present the results of a novel postural sway ratio (SR) analysis in patients with Parkinson's disease (PD) and age-matched healthy subjects. The sway ratios have been assessed based upon center of foot-pressure (CP) signals recorded in 55 parkinsonians (Hoehn and Yahr: 1-3) and 55 age-matched healthy volunteers while standing quiet with eyes open (EO) and then with eyes closed (EC). Complementing classical sway measure abnormalities, the SR exhibited a high discriminative power for all controlled factors: pathology, vision, and direction of sway. Both the anteroposterior (AP) and mediolateral (ML) sway ratios were significantly increased in PD patients when compared to the control group. An additional SR increase was observed in the response to eyes closure. The sway ratio changes documented here can be attributed to a progressive decline of a postural stability control due to pathology. In fact, a significant correlation between the mediolateral SR under EO conditions and Motor Exam (section III) score of the UPDRS was found. The mediolateral sway ratios computed for EO and EC conditions significantly correlated with the CP path length (r = .87) and the mean anteroposterior CP position within the base of support (r = .38). Both indices reflect postural stability decline and fall tendency # in parkinsonians. The tremor-type PD patients (N=34) showed more pronounced relationships between the mediolateral SR and selected items from the UPDRS scale, including: falls (Kendall Tau=.47, p < .05), rigidity (.45, p < .05), postural stability (retropulsion) (.52), and the Motor Exam score (.73). The anteroposterior SR correlated only with tremor (Kendal Tau = .77, p < .05). It seems that in force plate posturography the SR can be recommended as a single reliable measure that allows for a better quantitative assessment of postural stability impairments. Copyright © 2010 Elsevier B.V. All rights reserved.

Drooling in Parkinson's Disease: Evidence of a Role for Divided Attention.

PubMed

Reynolds, Hannah; Miller, Nick; Walker, Richard

2018-05-21

Drooling is a frequently reported symptom in Parkinson's Disease (PD) with significant psychosocial impact and negative health consequences including silent aspiration of saliva with the associated risk of respiratory infections. It is suggested that in PD drooling is associated with inefficient oropharyngeal swallowing which reduces the effective clearance of saliva rather than hyper-salivation. This is compounded by unintended mouth opening and flexed posture increasing anterior loss of saliva. It is reported to occur most frequently during cognitively distracting concurrent tasks suggesting an impact from divided attention in a dual-task situation. However, this supposition has not been systematically examined. This study assessed whether frequency of saliva swallows reduced, and drooling severity and frequency increased, when people with PD engaged in a cognitively distracting task. 18 patients with idiopathic PD reporting daytime drooling on the Unified Parkinson's Disease Rating Scale (UPDRS) were recruited. They completed the Radboud Oral Motor Inventory for PD saliva questionnaire and the Montreal Cognitive Assessment. UPDRS drooling score, disease stage, duration, gender, and age were recorded. Swallow frequency and drooling severity and frequency were measured at rest and during a distracting computer-based language task. There was no significant difference between drooling severity at rest and during distraction (Wilcoxon signed rank test z = - 1.724, p = 0.085). There was a significant difference between at rest and distraction conditions for both drooling frequency (Wilcoxon signed rank test z = - 2.041, p = 0.041) and swallow frequency (Wilcoxon signed rank test z = - 3.054, p = 0.002). Participants swallowed less frequently and drooled more often during the distraction task. The frequency of saliva swallows and drooling are affected by divided attention in a dual-task paradigm. Further studies are needed to explore the exact role of attention in saliva management and the clinical applications in assessment and treatment.

Tai Chi for Reducing Dual-task Gait Variability, a Potential Mediator of Fall Risk in Parkinson's Disease: A Pilot Randomized Controlled Trial.

PubMed

Vergara-Diaz, Gloria; Osypiuk, Kamila; Hausdorff, Jeffrey M; Bonato, Paolo; Gow, Brian J; Miranda, Jose Gv; Sudarsky, Lewis R; Tarsy, Daniel; Fox, Michael D; Gardiner, Paula; Thomas, Cathi A; Macklin, Eric A; Wayne, Peter M

2018-01-01

To assess the feasibility and inform design features of a fully powered randomized controlled trial (RCT) evaluating the effects of Tai Chi (TC) in Parkinson's disease (PD) and to select outcomes most responsive to TC assessed during off-medication states. Two-arm, wait-list controlled RCT. Tertiary care hospital. Thirty-two subjects aged 40-75 diagnosed with idiopathic PD within 10 years. Six-month TC intervention added to usual care (UC) versus UC alone. Primary outcomes were feasibility-related (recruitment rate, adherence, and compliance). Change in dual-task (DT) gait stride-time variability (STV) from baseline to 6 months was defined, a priori, as the clinical outcome measure of primary interest. Other outcomes included: PD motor symptom progression (Unified Parkinson's Disease Rating Scale [UPDRS]), PD-related quality of life (PDQ-39), executive function (Trail Making Test), balance confidence (Activity-Specific Balance Confidence Scale, ABC), and Timed Up and Go test (TUG). All clinical assessments were made in the off-state for PD medications. Thirty-two subjects were enrolled into 3 sequential cohorts over 417 days at an average rate of 0.08 subjects per day. Seventy-five percent (12/16) in the TC group vs 94% (15/16) in the UC group completed the primary 6-month follow-up assessment. Mean TC exposure hours overall: 52. No AEs occurred during or as a direct result of TC exercise. Statistically nonsignificant improvements were observed in the TC group at 6 months in DT gait STV (TC [20.1%] vs UC [-0.1%] group [effect size 0.49; P = .47]), ABC, TUG, and PDQ-39. UPDRS progression was modest and very similar in TC and UC groups. Conducting an RCT of TC for PD is feasible, though measures to improve recruitment and adherence rates are needed. DT gait STV is a sensitive and logical outcome for evaluating the combined cognitive-motor effects of TC in PD.

Subthalamic nucleus stimulation-induced regional blood flow responses correlate with improvement of motor signs in Parkinson disease.

PubMed

Karimi, M; Golchin, N; Tabbal, S D; Hershey, T; Videen, T O; Wu, J; Usche, J W M; Revilla, F J; Hartlein, J M; Wernle, A R; Mink, J W; Perlmutter, J S

2008-10-01

Deep brain stimulation of the subthalamic nucleus (STN DBS) improves motor symptoms in idiopathic Parkinson's disease, yet the mechanism of action remains unclear. Previous studies indicate that STN DBS increases regional cerebral blood flow (rCBF) in immediate downstream targets but does not reveal which brain regions may have functional changes associated with improved motor manifestations. We studied 48 patients with STN DBS who withheld medication overnight and underwent PET scans to measure rCBF responses to bilateral STN DBS. PET scans were performed with bilateral DBS OFF and ON in a counterbalanced order followed by clinical ratings of motor manifestations using Unified Parkinson Disease Rating Scale 3 (UPDRS 3). We investigated whether improvement in UPDRS 3 scores in rigidity, bradykinesia, postural stability and gait correlate with rCBF responses in a priori determined regions. These regions were selected based on a previous study showing significant STN DBS-induced rCBF change in the thalamus, midbrain and supplementary motor area (SMA). We also chose the pedunculopontine nucleus region (PPN) due to mounting evidence of its involvement in locomotion. In the current study, bilateral STN DBS improved rigidity (62%), bradykinesia (44%), gait (49%) and postural stability (56%) (paired t-tests: P < 0.001). As expected, bilateral STN DBS also increased rCBF in the bilateral thalami, right midbrain, and decreased rCBF in the right premotor cortex (P < 0.05, corrected). There were significant correlations between improvement of rigidity and decreased rCBF in the SMA (r(s) = -0.4, P < 0.02) and between improvement in bradykinesia and increased rCBF in the thalamus (r(s) = 0.31, P < 0.05). In addition, improved postural reflexes correlated with decreased rCBF in the PPN (r(s) = -0.38, P < 0.03). These modest correlations between selective motor manifestations and rCBF in specific regions suggest possible regional selectivity for improvement of different motor signs of Parkinson's disease.

Subthalamic nucleus stimulation-induced regional blood flow responses correlate with improvement of motor signs in Parkinson disease

PubMed Central

Karimi, M.; Golchin, N.; Tabbal, S. D.; Hershey, T.; Videen, T. O.; Wu, J.; Usche, J. W. M.; Revilla, F. J.; Hartlein, J. M.; Wernle, A. R.; Mink, J. W.

2008-01-01

Deep brain stimulation of the subthalamic nucleus (STN DBS) improves motor symptoms in idiopathic Parkinson's disease, yet the mechanism of action remains unclear. Previous studies indicate that STN DBS increases regional cerebral blood flow (rCBF) in immediate downstream targets but does not reveal which brain regions may have functional changes associated with improved motor manifestations. We studied 48 patients with STN DBS who withheld medication overnight and underwent PET scans to measure rCBF responses to bilateral STN DBS. PET scans were performed with bilateral DBS OFF and ON in a counterbalanced order followed by clinical ratings of motor manifestations using Unified Parkinson Disease Rating Scale 3 (UPDRS 3). We investigated whether improvement in UPDRS 3 scores in rigidity, bradykinesia, postural stability and gait correlate with rCBF responses in a priori determined regions. These regions were selected based on a previous study showing significant STN DBS-induced rCBF change in the thalamus, midbrain and supplementary motor area (SMA). We also chose the pedunculopontine nucleus region (PPN) due to mounting evidence of its involvement in locomotion. In the current study, bilateral STN DBS improved rigidity (62%), bradykinesia (44%), gait (49%) and postural stability (56%) (paired t-tests: P < 0.001). As expected, bilateral STN DBS also increased rCBF in the bilateral thalami, right midbrain, and decreased rCBF in the right premotor cortex (P < 0.05, corrected). There were significant correlations between improvement of rigidity and decreased rCBF in the SMA (rs = –0.4, P < 0.02) and between improvement in bradykinesia and increased rCBF in the thalamus (rs = 0.31, P < 0.05). In addition, improved postural reflexes correlated with decreased rCBF in the PPN (rs = –0.38, P < 0.03). These modest correlations between selective motor manifestations and rCBF in specific regions suggest possible regional selectivity for improvement of different motor signs of Parkinson's disease. PMID:18697909

Are there adaptive changes in the human brain of patients with Parkinson's disease treated with long-term deep brain stimulation of the subthalamic nucleus? A 4-year follow-up study with regional cerebral blood flow SPECT.

PubMed

Sestini, Stelvio; Pupi, Alberto; Ammannati, Franco; Silvia, Ramat; Sorbi, Sandro; Castagnoli, Antonio

2007-10-01

The aim of this follow-up study was to assess persistent motor and regional cerebral blood flow (rCBF) changes in patients with Parkinson's disease (PD) treated with high-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN). Ten PD patients with STN-DBS underwent three rCBF SPECT studies at rest, once preoperatively in the off-drug condition (T(0)), and twice postoperatively in the off-drug/off-stimulation conditions at 5 +/- 2 (T(1)) and 42 +/- 7 months (T(2)). Patients were assessed using the UPDRS, H&Y and S&E scales. SPM was used to investigate baseline rCBF changes from the preoperative condition to the postoperative conditions and the relationship between rCBF and UPDRS scores used as covariate of interest. Parkinsonian patients showed a clinical improvement which was significant only on follow-up at 42 months. The main effect of treatment from T(0) to T(1) was to produce baseline rCBF increases in the pre-supplementary motor area (pre-SMA), premotor cortex and somatosensory association cortex. From T(1) to T(2) a further baseline rCBF increase was detected in the pre-SMA (p < 0.0001). A correlation was detected between the slight improvement in motor scores and the rCBF increase in the pre-SMA (p < 0.0001), which is known to play a crucial role in clinical progression. Our study suggests the presence of adaptive functional changes in the human brain of PD patients treated with long-term STN-DBS. Such adaptive processes seem to occur in the pre-SMA and to play only a slightly beneficial role in terms of functional compensation of motor impairment.

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

PubMed

Martínez-Martin, Pablo; Carod-Artal, Francisco Javier; da Silveira Ribeiro, Luciola; Ziomkowski, Sofia; Vargas, Antonio Pedro; Kummer, Wladimir; Mesquita, Hudson Mourão

2008-08-15

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 (alpha = 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. (c) 2008 Movement Disorder Society.

Gray matter atrophy associated with mild cognitive impairment in Parkinson's disease.

PubMed

Chen, Fu-Xiang; Kang, De-Zhi; Chen, Fu-Yong; Liu, Ying; Wu, Gang; Li, Xun; Yu, Liang-Hong; Lin, Yuan-Xiang; Lin, Zhang-Ya

2016-03-23

The underlying pathology of brain leading to cognitive impairment in Parkinson's disease (PD) remains poorly understood. The aim of our study was to test the hypothesis that mild cognitive impairment (MCI) in PD may be related to atrophy of special gray matter regions. High-resolution T1-weighted magnetic resonance images of the brains and comprehensive cognitive function tests were acquired in 37 PD patients and 21 healthy controls (HC) from September 2013 to October 2014. Patients were divided into two groups: PD with MCI (PD-MCI, n=18) and PD with normal cognition (PDNC, n=19). Gray matter density differences were analyzed using voxel-based morphometry (VBM). VBM and cognitive results, UPDRS scores and Hoehn-Yahr stages were compared between PD-MCI, PDCN and HC group, and correlation analyses were performed between those brain areas and cognition scores, UPDRS scores and disease duration, which showed significant group differences. The demographic data and motor severity among three groups were similar. However, comprehensive cognitive function results were more severe in PD-MCI than the other two groups. Compared to the HC group, the PDNC group showed reductions in gray matter density in frontal, temporal, parietal, bilateral insula lobes and many other regions of brain. Besides above changes, the PD-MCI group also revealed gray matter concentration decrease in left hippocampus and thalamus, and these changes still remained when compared with the PDNC group. The HC group did not show any more areas of atrophy in gray matter than others. Gray matter loss in PD represented significant correlations with global cognitive scores, motor severity or disease duration in some of these atrophic regions. The initial stages of cognitive function decline in patients with PD is closely associated with gray matter atrophy in left hippocampus and thalamus. These two regions may serve as potential imaging biomarkers for PD-MCI. Copyright © 2016. Published by Elsevier Ireland Ltd.

Clinical Correlates of Apathy in Patients Recently Diagnosed with Parkinson's Disease: The ANIMO Study

PubMed Central

Cubo, Esther; Benito-León, Julián; Coronell, Carlos; Armesto, Diana

2012-01-01

Objective Little is known about apathy in the early stages of Parkinson's disease (PD). We determined the clinical correlates of apathy in a large representative sample of patients recently diagnosed with PD (ANIMO study). Methods PD patients, diagnosed within 2 years of inclusion, were recruited in 102 outpatient clinics situated in 82 populations throughout Spain. Apathy was quantified using the Lille Apathy Rating Scale (LARS). Clinical comparisons and correlations were performed using nonparametric tests. Regression analyses were used to test the association of clinical variables with apathy. Results We recruited 557 PD patients (60.3% men) with a mean age of 68.8 ± 9.7 years, and UPDRS motor score of 21.1 ± 10.8. Apathy only was diagnosed in 186 (33.4%), and apathy and depression in 215 patients (38.6%). Patients with higher comorbidity (OR = 1.10, 95% CI 1.01−1.20, p = 0.001), motor impairment (OR = 1.07, 95% CI 1.03−1.10, p < 0.0001), and lower education (OR = 2.16, 95% CI 1.21−;3.85, p = 0.009) had higher odds of having apathy, in contrast to patients living in a rural environment (OR = 0.35, 95% CI 0.32–0.85, p = 0.01), and left predominant PD motor laterality (OR = 0.34, 95% CI 0.13–0.88, p = 0.01). LARS scores were significantly correlated with UPDRS motor scores (rs = 0.44, p < 0.001), predominantly with axial score (rs = 0.43, p < 0.001). Conclusions In PD, apathy is a very common and disabling nonmotor symptom separable from depression. Patients living in a rural environment, with lower comorbidity and motor impairment, higher education background, and left predominant PD motor laterality are at lower risk of suffering from apathy. PMID:22236943

Does Cognitive Impairment Affect Rehabilitation Outcome in Parkinson’s Disease?

PubMed Central

Ferrazzoli, Davide; Ortelli, Paola; Maestri, Roberto; Bera, Rossana; Giladi, Nir; Ghilardi, Maria Felice; Pezzoli, Gianni; Frazzitta, Giuseppe

2016-01-01

Background: The cognitive status is generally considered as a major determinant of rehabilitation outcome in Parkinson’s disease (PD). No studies about the effect of cognitive impairment on motor rehabilitation outcomes in PD have been performed before. Objective: This study is aimed to evaluate the impact of cognitive decline on rehabilitation outcomes in patients with PD. Methods: We retrospectively identified 485 patients with PD hospitalized for a 4-week Multidisciplinary Intensive Rehabilitation Treatment (MIRT) between January 2014 and September 2015. According to Mini Mental State Examination (MMSE), patients were divided into: group 1—normal cognition (score 27–30), group 2—mild cognitive impairment (score 21–26), group 3—moderate or severe cognitive impairment (score ≤ 20). According to Frontal Assessment Battery (FAB), subjects were divided into patients with normal (score ≥13.8) and pathological (score <13.8) executive functions. The outcome measures were: Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Disability Scale (PDDS), Six Minutes Walking Test (6MWT), Timed Up and Go Test (TUG) and Berg Balance Scale (BBS). Results: All scales had worse values with the increase of cognitive impairment and passing from normal to pathological executive functions. After rehabilitation, all the outcome measures improved in all groups (p < 0.0001). Between groups, the percentage of improvement was significantly different for total UPDRS (p = 0.0009, best improvement in normal MMSE group; p = 0.019, best improvement in normal FAB group), and BBS (p < 0.0001, all pairwise comparisons significant, best improvement in patients with worse MMSE score; p < 0.0001, best improvement in patients with pathological FAB). TUG (p = 0.006) and BBS (p < 0.0001) improved in patients with pathological FAB score, more than in those with normal FAB score. Conclusions: Patients gain benefit in the rehabilitative outcomes, regardless of cognition. Our data suggest that rehabilitation could be effective also in Parkinsonian subjects with cognitive impairment, as well as with dysexecutive syndrome. PMID:27563290

Predictors of Recurrent Falls in People with Parkinson's Disease and Proposal for a Predictive Tool.

PubMed

Almeida, Lorena R S; Valenca, Guilherme T; Negreiros, Nádja N; Pinto, Elen B; Oliveira-Filho, Jamary

2017-01-01

Falls are a debilitating problem for people with Parkinson's disease (PD). To compare clinical and functional characteristics of non-fallers, single and recurrent fallers (≥2 falls); to determine predictors of time to second fall; and to develop a predictive tool for identifying people with PD at different categories of falls risk. Participants (n = 229) were assessed by disease-specific, self-report and balance measures and followed up for 12 months. Area under the receiver operating characteristic curves (AUC), Kaplan-Meier curves and log-rank test were performed. Selected predictors with p < 0.10 in univariate analysis were chosen to be entered into the Cox regression model. Eighty-four (37%) participants had ≥2 falls during the follow-up. Recurrent fallers significantly differed from single fallers. The final Cox model included history of ≥2 falls in the past year (Hazard Ratio [HR] = 3.94; 95% confidence interval [CI] 2.26-6.86), motor fluctuations (HR = 1.91; 95% CI 1.12-3.26), UPDRS activities of daily living (ADL) (HR = 1.10 per 1 point increase; 95% CI 1.06-1.14) and levodopa equivalent dose (LED) (HR = 1.09 per 100 mg increase; 95% CI 1.02-1.16). A 3-predictor tool included history of ≥2 falls in the past year, motor fluctuations and UPDRS ADL >12 points (AUC = 0.84; 95% CI 0.78-0.90). By adding LED >700 mg/day and Berg balance scale ≤49 points, a 5-predictor tool was developed (AUC = 0.86; 95% CI 0.81-0.92). Two predictive tools with moderate-to-high accuracy may identify people with PD at low, medium and high risk of falling recurrently within the next year. However, future studies to address external validation are required.

Effects of rotigotine transdermal patch in patients with Parkinson's disease presenting with non-motor symptoms - results of a double-blind, randomized, placebo-controlled trial.

PubMed

Antonini, A; Bauer, L; Dohin, E; Oertel, W H; Rascol, O; Reichmann, H; Schmid, M; Singh, P; Tolosa, E; Chaudhuri, K Ray

2015-10-01

Non-motor symptoms (NMS) of Parkinson's disease (PD) have a major impact on health-related quality of life. This is the first randomized controlled trial to use the NMS Scale (NMSS) as a primary outcome to assess treatment effects on NMS in PD. In this double-blind trial (NCT01300819), patients with PD and a total NMSS score ≥40 were randomized (2:1) to rotigotine or placebo, titrated over 1-7 weeks to optimal dose (≤8 mg/24 h for patients not receiving levodopa, ≤16 mg/24 h for patients receiving levodopa), maintained for 12 weeks. The primary outcome was change in NMSS total score from baseline to end of maintenance. Secondary outcomes were the nine NMSS domains, Unified Parkinson's Disease Rating Scale (UPDRS) III (motor) and the 39-item Parkinson's Disease Questionnaire (PDQ-39). In total, 283/349 (81.1%) randomized patients completed the trial; 211 rotigotine and 122 placebo were included in the full analysis set. The NMSS total score decreased by 23 (rotigotine) and 19 (placebo) points; the treatment difference was not statistically significant (-3.58; 95% confidence interval -8.43, 1.26; P = 0.147). Numerically greater than placebo improvements were detected in the 'mood/apathy' and 'miscellaneous' NMSS domains (P < 0.05). Treatment differences in UPDRS III (-2.60; -4.27, -0.92; P = 0.002) and PDQ-39 (-2.79; -5.21, -0.37; P = 0.024) favoured rotigotine. Adverse events reported more frequently with rotigotine were nausea, application site reactions, somnolence and headache. Rotigotine improvement in the multi-domain NMSS total score was not superior to placebo. A different sensitivity of individual NMSS domains to dopaminergic therapy and a large placebo effect may have contributed to these findings. © 2015 EAN.

SPECT-evaluation of the monoamine uptake site ligand [123I](1R)-2-beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane ([123I]beta-CIT) in untreated patients with suspicion of Parkinson disease.

PubMed

Eising, E G; Müller, T T; Zander, C; Kuhn, W; Farahati, J; Reiners, C; Coenen, H H

1997-10-01

For a few years, data on SPECT-imaging of dopamine transporters with the cocaine derivate [123I](1R)-2-beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane ([123I] beta-CIT) have been reported mostly in healthy subjects or animals. This study reflects our preliminary results with SPECT-imaging of dopamine transporters using the cocaine analogue 123-beta-CIT in patients with untreated (de novo) parkinsonism. In 33 patients with clinical suspicion of Parkinson disease and 5 healthy controls, SPECT-imaging of dopamine transporters was performed 1, 4, and 24 hours after injection of 180 MBq of 123I-beta-CIT, which was generated by iododestannylation. None of the patients or controls had been treated before with neuroleptical drugs or any other pharmaceuticals with known binding to the dopamine transporters. Clinical symptoms were staged by the scales Hoehn-Yahr (HYS), Unified Parkinson Disease Rating Scale (UPDRS), and the self-rating scale of Beck depression inventory (BDI). For evaluation, striatal/cerebellar ratios were calculated to every time point. Significant correlations of 123I-beta-CIT uptake could be stated compared to UPDRS, HYS, and BDI values (Spearman correlation, p < 0.05). The symptoms of rigor and akinesia showed a significant correlation with the beta-CIT uptake, whereas the symptom of tremor failed, which may be caused by the location of tremor symptoms out of the striatum. Comparing the controls, a significant (p < 0.01) decrease of tracer uptake in parkinsonian patients is stated on the images at 24 hours p.i. In our patients, tracer uptake does not depend significantly on duration of disease and age. 123I-beta-CIT seems to be a promising tool in imaging of untreated parkinsonian patient.

14 CFR Appendix A to Part 91 - Category II Operations: Manual, Instruments, Equipment, and Maintenance

Code of Federal Regulations, 2010 CFR

2010-01-01

... authorization for the type aircraft checked. (3) A schedule that provides for the performance of bench checks..., Equipment, and Maintenance A Appendix A to Part 91 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION... Maintenance 1. Category II Manual (a) Application for approval. An applicant for approval of a Category II...

14 CFR Appendix A to Part 91 - Category II Operations: Manual, Instruments, Equipment, and Maintenance

Code of Federal Regulations, 2013 CFR

2013-01-01

... authorization for the type aircraft checked. (3) A schedule that provides for the performance of bench checks..., Equipment, and Maintenance A Appendix A to Part 91 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION... Maintenance 1. Category II Manual (a) Application for approval. An applicant for approval of a Category II...

14 CFR Appendix A to Part 91 - Category II Operations: Manual, Instruments, Equipment, and Maintenance

Code of Federal Regulations, 2012 CFR

2012-01-01

... authorization for the type aircraft checked. (3) A schedule that provides for the performance of bench checks..., Equipment, and Maintenance A Appendix A to Part 91 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION... Maintenance 1. Category II Manual (a) Application for approval. An applicant for approval of a Category II...

14 CFR Appendix A to Part 91 - Category II Operations: Manual, Instruments, Equipment, and Maintenance

Code of Federal Regulations, 2014 CFR

2014-01-01

... authorization for the type aircraft checked. (3) A schedule that provides for the performance of bench checks..., Equipment, and Maintenance A Appendix A to Part 91 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION... Maintenance 1. Category II Manual (a) Application for approval. An applicant for approval of a Category II...

14 CFR Appendix A to Part 91 - Category II Operations: Manual, Instruments, Equipment, and Maintenance

Code of Federal Regulations, 2011 CFR

2011-01-01

... authorization for the type aircraft checked. (3) A schedule that provides for the performance of bench checks..., Equipment, and Maintenance A Appendix A to Part 91 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION... Maintenance 1. Category II Manual (a) Application for approval. An applicant for approval of a Category II...

40 CFR Appendix B to Subpart A of... - Class II Controlled Substances a

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 18 2014-07-01 2014-07-01 false Class II Controlled Substances a B Appendix B to Subpart A of Part 82 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED..., Subpt. A, App. B Appendix B to Subpart A of Part 82—Class II Controlled Substances a Controlled...

40 CFR Appendix II to Part 1045 - Duty Cycles for Propulsion Marine Engines

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 32 2010-07-01 2010-07-01 false Duty Cycles for Propulsion Marine... Pt. 1045, App. II Appendix II to Part 1045—Duty Cycles for Propulsion Marine Engines (a) The following duty cycle applies for discrete-mode testing: E4 Mode No. Enginespeed 1 Torque(percent) 2...

40 CFR Appendix II to Part 1039 - Steady-State Duty Cycles

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 32 2010-07-01 2010-07-01 false Steady-State Duty Cycles II Appendix... Appendix II to Part 1039—Steady-State Duty Cycles (a) The following duty cycles apply for constant-speed engines: (1) The following duty cycle applies for discrete-mode testing: D2 mode number Engine speed...

Coordinator(a) de Servicios Clinicos. Parte I (Unidad I-IV). Parte II (Unidad V-VI). Guia. Documento de Trabajo (Clinical Services Coordinator. Part I. Units I-IV. Part II. Units V-VI. Guide. Working Document).

ERIC Educational Resources Information Center

Puerto Rico State Dept. of Education, Hato Rey. Area for Vocational and Technical Education.

This guide is intended for instructing secondary students in the occupation of clinical services coordinator in a hospital. The first part contains four units on the following subjects: the occupation of clinical services coordinator; interpersonal relationships; ethical/legal aspects; and communications (telephone, intercom, and others). For each…

Pioglitazone in early Parkinson's disease: a phase 2, multicentre, double-blind, randomised trial

PubMed Central

2015-01-01

Summary Background A systematic assessment of potential disease-modifying compounds for Parkinson's disease concluded that pioglitazone could hold promise for the treatment of patients with this disease. We assessed the effect of pioglitazone on the progression of Parkinson's disease in a multicentre, double-blind, placebo-controlled, futility clinical trial. Methods Participants with the diagnosis of early Parkinson's disease on a stable regimen of 1 mg/day rasagiline or 10 mg/day selegiline were randomly assigned (1:1:1) to 15 mg/day pioglitazone, 45 mg/day pioglitazone, or placebo. Investigators were masked to the treatment assignment. Only the statistical centre and the central pharmacy knew the treatment name associated with the randomisation number. The primary outcome was the change in the total Unified Parkinson's Disease Rating Scale (UPDRS) score between the baseline and 44 weeks, analysed by intention to treat. The primary null hypothesis for each dose group was that the mean change in UPDRS was 3 points less than the mean change in the placebo group. The alternative hypothesis (of futility) was that pioglitazone is not meaningfully different from placebo. We rejected the null if there was significant evidence of futility at the one-sided alpha level of 0.10. The study is registered at ClinicalTrials.gov, number NCT01280123. Findings 210 patients from 35 sites in the USA were enrolled between May 10, 2011, and July 31, 2013. The primary analysis included 72 patients in the 15 mg group, 67 in the 45 mg group, and 71 in the placebo group. The mean total UPDRS change at 44 weeks was 4.42 (95% CI 2.55–6.28) for 15 mg pioglitazone, 5.13 (95% CI 3.17–7.08) for 45 mg pioglitazone, and 6.25 (95% CI 4.35–8.15) for placebo (higher change scores are worse). The mean difference between the 15 mg and placebo groups was −1.83 (80% CI −3.56 to −0.10) and the null hypothesis could not be rejected (p=0.19). The mean difference between the 45 mg and placebo groups was −1.12 (80% CI −2.93 to 0.69) and the null hypothesis was rejected in favour of futility (p=0.09). Planned sensitivity analyses of the primary outcome, using last value carried forward (LVCF) to handle missing data and using the completers' only sample, suggested that the 15 mg dose is also futile (p=0.09 for LVCF, p=0.09 for completers) but failed to reject the null hypothesis for the 45 mg dose (p=0.12 for LVCF, p=0.19 for completers). Six serious adverse events occurred in the 15 mg group, nine in the 45 mg group, and three in the placebo group; none were thought to be definitely or probably related to the study interventions. Interpretation These findings suggest that pioglitazone at the doses studied here is unlikely to modify progression in early Parkinson's disease. Further study of pioglitazone in a larger trial in patients with Parkinson's disease is not recommended. Funding National Institute of Neurological Disorders and Stroke. PMID:26116315

Evaluation of estimated energy conservation measure costs and benefits in the residential multifamily sector

NASA Astrophysics Data System (ADS)

1982-09-01

Supporting data for a policy review to determine how the multifamily buildings subsector is responding to market signals was sought. What role, if any, the federal government should play in encouraging conservation in multifamily buildings is discussed. The policy review seeks to develop an understanding of the current level of and trends in energy conservation activity in multifamily housing. The availability of the required data is determined and information in a form which facilitates its use by policy analysts is compiled. The results are presented in four parts. Part I provides an overview. Part II presents, in tabular form, the cost of selected retrofit items and the resulting energy and cost savings. As an aid to understanding the data in Part II, the salient assumptions underlying the data are also included in this part. Part III describes how the data in Part II were developed.

40 CFR Table II-1 to Subpart II of... - Emission Factors

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 21 2014-07-01 2014-07-01 false Emission Factors II Table II-1 to Subpart II of Part 98 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Industrial Wastewater Treatment Pt. 98, Subpt. II, Table II-1...

40 CFR Table II-1 to Subpart II of... - Emission Factors

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 22 2013-07-01 2013-07-01 false Emission Factors II Table II-1 to Subpart II of Part 98 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING Industrial Wastewater Treatment Pt. 98, Subpt. II, Table II-1...

42 CFR 423.509 - Termination of contract by CMS.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Part D plan in writing 90 days before the intended date of the termination. (ii) The Part D plan... sponsor; (B) The Part D plan sponsor experiences financial difficulties so severe that its ability to make...)(4) of this section. (ii) CMS notifies the MA organization in writing that its contract will be...

5 CFR 330.602 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... equivalent) or below who: (i) Received a reduction in force (RIF) separation notice under part 351 of this... positions; and (ii) Received a RIF separation notice under part 351 of this chapter or a notice of proposed...); or (ii) Received a RIF notice of separation under part 351 of this chapter or a notice of proposed...

5 CFR 330.602 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... equivalent) or below who: (i) Received a reduction in force (RIF) separation notice under part 351 of this... positions; and (ii) Received a RIF separation notice under part 351 of this chapter or a notice of proposed...); or (ii) Received a RIF notice of separation under part 351 of this chapter or a notice of proposed...

5 CFR 330.602 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... equivalent) or below who: (i) Received a reduction in force (RIF) separation notice under part 351 of this... positions; and (ii) Received a RIF separation notice under part 351 of this chapter or a notice of proposed...); or (ii) Received a RIF notice of separation under part 351 of this chapter or a notice of proposed...

Market Analysis and Consumer Impacts Source Document. Part II. Review of Motor Vehicle Market and Consumer Expenditures on Motor Vehicle Transportation

DOT National Transportation Integrated Search

1980-12-01

This source document on motor vehicle market analysis and consumer impacts consists of three parts. Part II consists of studies and review on: motor vehicle sales trends; motor vehicle fleet life and fleet composition; car buying patterns of the busi...

Calculus of Elementary Functions, Part II. Teacher's Commentary. Revised Edition.

ERIC Educational Resources Information Center

Herriot, Sarah T.; And Others

This course is intended for students who have a thorough knowledge of college preparatory mathematics, including algebra, axiomatic geometry, trigonometry, and analytic geometry. This teacher's guide is for Part II of the course. It is designed to follow Part I of the text. The guide contains background information, suggested instructional…

Calculus of Elementary Functions, Part II. Student Text. Revised Edition.

ERIC Educational Resources Information Center

Herriot, Sarah T.; And Others

This course is intended for students who have a thorough knowledge of college preparatory mathematics, including algebra, axiomatic geometry, trigonometry, and analytic geometry. This text, Part II, contains material designed to follow Part I. Chapters included in this text are: (6) Derivatives of Exponential and Related Functions; (7) Area and…

The year 2012 in the European Heart Journal-Cardiovascular Imaging. Part II.

PubMed

Plein, Sven; Knuuti, Juhani; Edvardsen, Thor; Saraste, Antti; Piérard, Luc A; Maurer, Gerald; Lancellotti, Patrizio

2013-07-01

The part II of the best of the European Heart Journal - Cardiovascular Imaging in 2012 specifically focuses on studies of valvular heart diseases, heart failure, cardiomyopathies, and congenital heart diseases.

Methods of Responsibly Managing End-of-Life Foams and Plastics Containing Flame Retardants: Part II.

PubMed

Lucas, Donald; Petty, Sara M; Keen, Olya; Luedeka, Bob; Schlummer, Martin; Weber, Roland; Yazdani, Ramin; Riise, Brian; Rhodes, James; Nightingale, Dave; Diamond, Miriam L; Vijgen, John; Lindeman, Avery; Blum, Arlene; Koshland, Catherine P

2018-06-01

This is Part II of a review covering the wide range of issues associated with all aspects of the use and responsible disposal of foam and plastic wastes containing toxic or potentially toxic flame retardants. We identify basic and applied research needs in the areas of responsible collection, pretreatment, processing, and management of these wastes. In Part II, we explore alternative technologies for the management of halogenated flame retardant (HFR) containing wastes, including chemical, mechanical, and thermal processes for recycling, treatment, and disposal.

Caring communications: how technology enhances interpersonal relations, Part II.

PubMed

Simpson, Roy L

2008-01-01

Part I of this 2-part series about technology's role in interpersonal communications examined how humans interact; proposed a caring theory of communication, collaboration, and conflict resolution; and delineated ways that technology--in general--supports this carative model of interpersonal relations. Part II will examine the barriers to adoption of carative technologies, describe the core capabilities required to overcome them, and discuss specific technologies that can support carative interpersonal relationships.

The relation between plasma α-synuclein level and clinical symptoms or signs of Parkinson's disease.

PubMed

Malec-Litwinowicz, Michalina; Plewka, Andrzej; Plewka, Danuta; Bogunia, Edyta; Morek, Michał; Szczudlik, Andrzej; Szubiga, Michał; Rudzińska-Bar, Monika

2018-03-01

Parkinson disease (PD) is the common neurodegenerative disease. α-Synuclein (ASN), main aggregating protein in neural cells of CNS in PD, was found in peripheral fluids. Testing ASN in plasma is potential test for diagnose PD, but previous studies are controversial. The aim of this study was to investigate if plasma ASN level may be a valuable biomarker, is the level of plasma ASN concentration different in various motor subtypes of diseases, is there a relation between the level of plasma ASN and the severity of motor symptoms. Patients with PD hospitalized in Neurology Department, Medical College were performed sequencing the 8th and 9th exon of GBA gene. Next plasma ASN level was tested in 58 patients with sequenced GBA gene and in 38 healthy volunteers (HV), matched by the age (respectively 68.43 vs. 64.57 years of age) and sex (female %, respectively: 43.10 vs.44.74). Patients were assessed with the scales: UPDRS (II, III, IV), Hoehn-Yahr (HY) and qualified to PIGD or TD subtype. For homogeneity of the group patients with GBA mutation were excluded from the analysis. The ASN level did not differ between patients and HV (respectively: 4.53 vs. 3.73ng/ml) and between patients with different subtypes. There was inverse correlation between ASN and HY in PIGD subtype. Plasma ASN level is not valuable marker of the disease. It does not differ in subtypes of the disease. There is relation between plasma ASN level and the severity of the disease in PIGD subtype. Copyright © 2017. Published by Elsevier Urban & Partner Sp. z o.o.

[Care-Dependency in Parkinson's Disease: More Frequent than Assumed?].

PubMed

Riedel, O

2015-06-01

Parkinson's disease (PD) increases the risk of care-dependency (CDP). While motor functions worsen continuously, the assignment of patients to CDP occurs categorically. It is unknown how many patients are already sufficiently severely impaired to be categorised as CDP yet do not have an officially acknowledged level of CDP. A random sample of 1,449 PD outpatients was clinically characterised by office-based neurologists, including impairments of activities of daily living (ADL with the Unified Parkinson's Disease Rating scale (UPDRS subscale II) as well as regarding the presence of dementia according to DSM-IV criteria and the Mini-Mental State Exam (MMSE). Depression was screened for with the Montgomery-Asberg Depression Rating Scale (MADRS). For each patient the officially acknowledged level of CDP was documented; for patients without official CDP level, the clinician appraised whether the patient was care-dependent anyhow. 266 patients (18.3%) were officially acknowledged as care-dependent, while n=121 patients (8.5%) were not, yet were appraised to be care-dependent according to the clinician. Compared to non-CDP patients, they differed on every measure considered. Compared to patients with an official CDP, their PD duration was significantly shorter (6.0 vs. 8.0 years, p<0.01) and they were less severely impaired in ADL (13.3 vs. 15.5, p<0.01). They did not differ regarding the rates of dementia (52.9 vs. 44.9%, p=0.203) or depression according to the MADRS (13.1 vs. 13.1, p=0.989). ADL impairments are the most important predictor for CDP while dementia and depression are not considered despite the impairments that are additionally caused by them. © Georg Thieme Verlag KG Stuttgart · New York.

Italian validation of the Belastungsfragebogen Parkinson kurzversion (BELA-P-k): a disease-specific questionnaire for evaluation of the subjective perception of quality of life in parkinson's disease.

PubMed

Ortelli, Paola; Maestri, Roberto; Zarucchi, Marianna; Cian, Veronica; Urso, Elisa; Giacomello, Francesca; Ferrazzoli, Davide; Frazzitta, Giuseppe

2017-01-01

Quality of life (QoL) is the sense of well-being perceived by people. The improvement of parkinsonian patient's QoL is a crucial goal for clinicians involved in rehabilitative care. In order to provide an appropriate endpoint for the assessment of the effectiveness of rehabilitation treatments on QoL of patients with Parkinson's Disease (PD), in this study we have first translated and then validated the Belastungsfragebogen Parkinson kurzversion (BELA-P-k). This tool allows evaluating separately two crucial aspects: i) the loss of personal autonomy in activities of daily life and ii) the psychological and psychosocial impact of the disease. The BELA-P-k was translated from Dutch into Italian. Subsequently 202 PD patients filled out the questionnaire. Patients were also evaluated by using the Parkinson Disease Questionnaire -39 (PDQ39), the Unified Parkinson's Disease Rating Scale (UPDRS), the Mini Mental State Examination (MMSE) and the Frontal Assessment Battery (FAB). The internal consistency for total of two different scores Bothered by (Bb) and Need for Help (NfH) was excellent ( p  = 0.91) for both categories. The correlation between Bb and NfH categories was significant and strong, very-strong, ranging from 0.78 to 0.88 (all p  < 0.0001). Finally, the value of Spearman r for the relationship between Bb and NfH items and PDQ 39 values were significant ( p  ≤ 0.003). In conclusion, we validated the BELA-P-k and demonstrated that it is an appropriate and potentially useful tool for assessing QoL in the management of PD. This trial was retrospectively registered with ClinicalTrials.gov, NCT03073044.

Progression of motor and nonmotor features of Parkinson's disease and their response to treatment

PubMed Central

Vu, Thuy C.; Nutt, John G.; Holford, Nicholas H. G.

2012-01-01

AIMS (i) To describe the progression of the cardinal features of Parkinson's disease (PD); (ii) to investigate whether baseline PD subtypes explain disease progression; and (iii) to quantify the symptomatic and disease-modifying effects of anti-parkinsonian treatments. METHODS Data were available for 795 PD subjects, initially untreated, followed for up to 8 years. Cardinal features [tremor, rigidity, bradykinesia, and postural instability and gait disorder (PIGD)] were derived from the total unified Parkinson's disease rating scale (total UPDRS), cognitive status from the mini-mental status exam score (MMSE) and depression status from the Hamilton depression scale (HAM-D). Analysis was performed using a nonlinear mixed effects approach with an asymptotic model for natural disease progression. Treatment effects (i.e. symptomatic and disease modifying) were evaluated by describing changes in the natural history model parameters. RESULTS Tremor progressed more slowly (half-time of 3.9 years) than all other motor features (half-time 2–3 years). The MMSE progression was negligible, while HAM-D progressed with a half-time of 5 years. Levodopa had marked symptomatic effects on all features, but low potency for effect on PIGD (ED50 of 1237 mg day−1 compared with 7–24 mg day−1 for other motor and nonmotor features). Other anti-parkinsonian treatments had much smaller symptomatic effects. All treatments had disease-modifying effects on the cardinal features of PD. Baseline PD subtypes only explained small differences in disease progression. CONCLUSIONS This analysis indicates that tremor progresses more slowly than other cardinal features and that PIGD is less treatment responsive in early PD patients. There was no evidence of baseline PD subtypes as a clinically useful predictor of disease progression rate. Anti-parkinsonian treatments have symptomatic and disease-modifying effects on all major features of PD. PMID:22283961

Kick, Glide, Pole! Cross-Country Skiing Fun (Part II)

ERIC Educational Resources Information Center

Duoos, Bridget A.

2012-01-01

Part I of Kick, Glide, Pole! Cross-Country Skiing Fun, which was published in last issue, discussed how to select cross-country ski equipment, dress for the activity and the biomechanics of the diagonal stride. Part II focuses on teaching the diagonal stride technique and begins with a progression of indoor activities. Incorporating this fun,…

An Occupation and Participation Approach to Reading Intervention (OPARI) Part II: Pilot Clinical Application

ERIC Educational Resources Information Center

Grajo, Lenin C.; Candler, Catherine

2016-01-01

The Occupation and Participation Approach to Reading Intervention (OPARI) is an intervention approach for children with reading difficulties that emphasizes reading as an important occupation of children. Part I presented the theoretical basis of the OPARI. Part II describes a pilot clinical application of the OPARI. Guided by Schkade and…

76 FR 17781 - Guidance Under Section 1502; Amendment of Matching Rule for Certain Gains on Member Stock...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-31

... for part 1 continues to read in part as follows: Authority: 26 U.S.C. 7805. * * * 0 Par. 2. Section 1.1502-13 is amended by revising paragraphs (c)(6)(ii)(C)(2) and (c)(6)(ii)(D)(1) to read as follows: Sec. 1.1502-13 Intercompany transactions. * * * * * (c) * * * (6) * * * (ii) * * * (C) * * * (2) Effect...

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on Subthalamic Nucleus and Globus Pallidus Internus Deep Brain Stimulation for the Treatment of Patients With Parkinson's Disease: Executive Summary.

PubMed

Rughani, Anand; Schwalb, Jason M; Sidiropoulos, Christos; Pilitsis, Julie; Ramirez-Zamora, Adolfo; Sweet, Jennifer A; Mittal, Sandeep; Espay, Alberto J; Martinez, Jorge Gonzalez; Abosch, Aviva; Eskandar, Emad; Gross, Robert; Alterman, Ron; Hamani, Clement

2018-06-01

Is bilateral subthalamic nucleus deep brain stimulation (STN DBS) more, less, or as effective as bilateral globus pallidus internus deep brain stimulation (GPi DBS) in treating motor symptoms of Parkinson's disease, as measured by improvements in Unified Parkinson's Disease Rating Scale, part III (UPDRS-III) scores? Given that bilateral STN DBS is at least as effective as bilateral GPi DBS in treating motor symptoms of Parkinson's disease (as measured by improvements in UPDRS-III scores), consideration can be given to the selection of either target in patients undergoing surgery to treat motor symptoms. (Level I). Is bilateral STN DBS more, less, or as effective as bilateral GPi DBS in allowing reduction of dopaminergic medication in Parkinson's disease? When the main goal of surgery is reduction of dopaminergic medications in a patient with Parkinson's disease, then bilateral STN DBS should be performed instead of GPi DBS. (Level I). Is bilateral STN DBS more, less, or as effective as bilateral GPi DBS in treating dyskinesias associated with Parkinson's disease? There is insufficient evidence to make a generalizable recommendation regarding the target selection for reduction of dyskinesias. However, when the reduction of medication is not anticipated and there is a goal to reduce the severity of "on" medication dyskinesias, the GPi should be targeted. (Level I). Is bilateral STN DBS more, less, or as effective as bilateral GPi DBS in improving quality of life measures in Parkinson's disease? When considering improvements in quality of life in a patient undergoing DBS for Parkinson's disease, there is no basis to recommend bilateral DBS in 1 target over the other. (Level I). Is bilateral STN DBS associated with greater, lesser, or a similar impact on neurocognitive function than bilateral GPi DBS in Parkinson disease? If there is significant concern about cognitive decline, particularly in regards to processing speed and working memory in a patient undergoing DBS, then the clinician should consider using GPi DBS rather than STN DBS, while taking into consideration other goals of surgery. (Level I). Is bilateral STN DBS associated with a higher, lower, or similar risk of mood disturbance than GPi DBS in Parkinson's disease? If there is significant concern about the risk of depression in a patient undergoing DBS, then the clinician should consider using pallidal rather than STN stimulation, while taking into consideration other goals of surgery. (Level I). Is bilateral STN DBS associated with a higher, lower, or similar risk of adverse events compared to GPi DBS in Parkinson's disease? There is insufficient evidence to recommend bilateral DBS in 1 target over the other in order to minimize the risk of surgical adverse events.  The full guideline can be found at: https://www.cns.org/guidelines/deep-brain-stimulation-parkinsons-disease.

Corporate liability: security and violence--Part II.

PubMed

Fiesta, J

1996-04-01

A hospital can be held liable for injuries resulting from failure to provide adequate, reasonable security Part II of "corporate Liability: Security and Violence" addresses negligent hiring and supervision practices, injury and domestic violence in the workplace and communication procedures.

Fourier Transform Infrared Spectroscopy: Part II. Advantages of FT-IR.

ERIC Educational Resources Information Center

Perkins, W. D.

1987-01-01

This is Part II in a series on Fourier transform infrared spectroscopy (FT-IR). Described are various advantages of FT-IR spectroscopy including energy advantages, wavenumber accuracy, constant resolution, polarization effects, and stepping at grating changes. (RH)

Sporting Goods. Part I: Hunting and Fishing Equipment and Part II: Athletic, Marine, and Camping Equipment. A Distributive Education Manual.

ERIC Educational Resources Information Center

Day, Bill D., Comp.

These manuals were prepared to introduce students to the fundamentals of hunting and fishing (Part I) and sports requiring athletic, marine and camping equipment (Part II). The sports salesman is in the position of offering a service to the customer, and he can best do so by understanding the sports and the variety of products which may be sold to…

Interactive Macroeconomics

NASA Astrophysics Data System (ADS)

Di Guilmi, Corrado; Gallegati, Mauro; Landini, Simone

2017-04-01

Preface; List of tables; List of figures, 1. Introduction; Part I. Methodological Notes and Tools: 2. The state space notion; 3. The master equation; Part II. Applications to HIA Based Models: 4. Financial fragility and macroeconomic dynamics I: heterogeneity and interaction; 5. Financial fragility and macroeconomic Dynamics II: learning; Part III. Conclusions: 6. Conclusive remarks; Part IV. Appendices and Complements: Appendix A: Complements to Chapter 3; Appendix B: Solving the ME to solve the ABM; Appendix C: Specifying transition rates; Index.

Design of two-dimensional channels with prescribed velocity distributions along the channel walls

NASA Technical Reports Server (NTRS)

Stanitz, John D

1953-01-01

A general method of design is developed for two-dimensional unbranched channels with prescribed velocities as a function of arc length along the channel walls. The method is developed for both compressible and incompressible, irrotational, nonviscous flow and applies to the design of elbows, diffusers, nozzles, and so forth. In part I solutions are obtained by relaxation methods; in part II solutions are obtained by a Green's function. Five numerical examples are given in part I including three elbow designs with the same prescribed velocity as a function of arc length along the channel walls but with incompressible, linearized compressible, and compressible flow. One numerical example is presented in part II for an accelerating elbow with linearized compressible flow, and the time required for the solution by a Green's function in part II was considerably less than the time required for the same solution by relaxation methods in part I.

40 CFR Appendix II to Part 257 - Appendix II to Part 257

Code of Federal Regulations, 2014 CFR

2014-07-01

... are only add-on in nature. Beta ray irradiation: Sludge is irradiated with beta rays from an accelerator at dosages of at least 1.0 megarad at room temperature (ca. 20 °C). Gamma ray irradiation: Sludge...

40 CFR Appendix II to Part 257 - Appendix II to Part 257

Code of Federal Regulations, 2010 CFR

2010-07-01

... are only add-on in nature. Beta ray irradiation: Sludge is irradiated with beta rays from an accelerator at dosages of at least 1.0 megarad at room temperature (ca. 20 °C). Gamma ray irradiation: Sludge...

40 CFR Appendix II to Part 257 - Appendix II to Part 257

Code of Federal Regulations, 2011 CFR

2011-07-01

... are only add-on in nature. Beta ray irradiation: Sludge is irradiated with beta rays from an accelerator at dosages of at least 1.0 megarad at room temperature (ca. 20 °C). Gamma ray irradiation: Sludge...

40 CFR Appendix II to Part 257 - Appendix II to Part 257

Code of Federal Regulations, 2012 CFR

2012-07-01

... are only add-on in nature. Beta ray irradiation: Sludge is irradiated with beta rays from an accelerator at dosages of at least 1.0 megarad at room temperature (ca. 20 °C). Gamma ray irradiation: Sludge...

40 CFR Appendix II to Part 257 - Appendix II to Part 257

Code of Federal Regulations, 2013 CFR

2013-07-01

... are only add-on in nature. Beta ray irradiation: Sludge is irradiated with beta rays from an accelerator at dosages of at least 1.0 megarad at room temperature (ca. 20 °C). Gamma ray irradiation: Sludge...

Higher Education in Poland Part II: Rules of Admissions, Student Activities, and Curriculums. Bulletin, 1964, No. 22. OE-14099

ERIC Educational Resources Information Center

Rosen, Seymour M.; Apanasewicz, Nellie

1964-01-01

The previously published "Higher Education in Poland, Part I: Organization and Administration," and the present volume constitute an Office of Education study on the Polish system of higher learning. Part II explains the functioning of Polish institutions under control of the Ministry of Higher Education and other ministries, and…

The Mental Health Recovery Movement and Family Therapy, Part II: A Collaborative, Appreciative Approach for Supporting Mental Health Recovery

ERIC Educational Resources Information Center

Gehart, Diane R.

2012-01-01

A continuation of Part I, which introduced mental health recovery concepts to family therapists, Part II of this article outlines a collaborative, appreciative approach for working in recovery-oriented contexts. This approach draws primarily upon postmodern therapies, which have numerous social justice and strength-based practices that are easily…

Institutional Self-Analysis and Long-Range Planning in a Small Liberal Arts College. Part II-- Study Procedure.

ERIC Educational Resources Information Center

Frame, Stanley M.

In the Spring of 1969, Bethany Nazarene College started an intensive self evaluation effort, called the Ten-Year Advance Study. Part I of the report, the Study Design, was published in October 1969. This study, Part II, relates the study activities, the methodology, and sources consulted. The effort involved over 120 administrators, faculty,…

Learning To Read with Private Pete & Sailor Sam in World War II.

ERIC Educational Resources Information Center

Sticht, Thomas G.

Since thousands of the men who entered military service during World War II were illiterate, the Army developed an "Army Reader," a four-part series featuring Private Pete, that led learners through literacy levels 1-4. Part 1 introduced Private Pete and talked about the things the men experienced when they entered the Army. Part 2…

Verbal Memory Decline following DBS for Parkinson’s Disease: Structural Volumetric MRI Relationships

PubMed Central

Geevarghese, Ruben; Lumsden, Daniel E.; Costello, Angela; Hulse, Natasha; Ayis, Salma; Samuel, Michael; Ashkan, Keyoumars

2016-01-01

Background Parkinson’s disease is a chronic degenerative movement disorder. The mainstay of treatment is medical. In certain patients Deep Brain Stimulation (DBS) may be offered. However, DBS has been associated with post-operative neuropsychology changes, especially in verbal memory. Objectives Firstly, to determine if pre-surgical thalamic and hippocampal volumes were related to verbal memory changes following DBS. Secondly, to determine if clinical factors such as age, duration of symptoms or motor severity (UPDRS Part III score) were related to verbal memory changes. Methods A consecutive group of 40 patients undergoing bilateral Subthalamic Nucleus (STN)-DBS for PD were selected. Brain MRI data was acquired, pre-processed and structural volumetric data was extracted using FSL. Verbal memory test scores for pre- and post-STN-DBS surgery were recorded. Linear regression was used to investigate the relationship between score change and structural volumetric data. Results A significant relationship was demonstrated between change in List Learning test score and thalamic (left, p = 0.02) and hippocampal (left, p = 0.02 and right p = 0.03) volumes. Duration of symptoms was also associated with List Learning score change (p = 0.02 to 0.03). Conclusion Verbal memory score changes appear to have a relationship to pre-surgical MRI structural volumetric data. The findings of this study provide a basis for further research into the use of pre-surgical MRI to counsel PD patients regarding post-surgical verbal memory changes. PMID:27557088

An exploratory study of live vs. web-based delivery of a phlebotomy program.

PubMed

Fydryszewski, Nadine A; Scanlan, Craig; Guiles, H Jesse; Tucker, Ann

2010-01-01

Changes in student population and increased Web-based education offerings provided the impetus to assess pedagogy, cognitive outcomes and perceptions of course quality. This study explored cognitive outcomes and students' perception of course quality related to the Seven Principles for Good Practice in Undergraduate Education between live classroom delivery, compared to a Web-based delivery of a phlebotomy program. Quasi-experimental; students self-selected to enroll in live or Web-based program. For cognitive outcomes, no significant difference was found between the groups. Student perception of course quality differed only for Principle One (student-instructor contact). Students in the live classroom rated Principle One higher for the Part I course compared to the Web-based group. For the Part II course, there was no significant difference in perception of course quality related to any of the Seven Principles. The more constructivist pedagogy in the Part II course did not improve cognitive outcomes however, it may have contributed to knowledge retention. The live group rated Principle One in the Part II course evaluation relatively the same as they did for the Part I course evaluation. However, the Web-based group rated Principle One considerable higher for the Part II course than for Part I course. Future studies with a larger sample could explore improved course quality assessment instruments.

Matematicas Para El Primer Ciclo Secundario, Volumen II (Parte 2). Traduccion Preliminar de la Edicion en Ingles Revisada. (Mathematics for Junior High School, Volume II, Part 2. Preliminary Translation of the Revised English Edition).

ERIC Educational Resources Information Center

Anderson, R. D.; And Others

This is part two of a two-part SMSG mathematics text for junior high school students. Key ideas emphasized are structure of arithmetic from an algebraic viewpoint, the real number system as a progressing development, and metric and non-metric relations in geometry. Chapter topics include real numbers, similar triangles, variation, polyhedrons,…

Actualizing system benefits--Part II.

PubMed

Zinn, T K; DiGiulio, L W

1988-05-01

Do benefits impact the psychology of the information system buying decision? Is system success tied to achieving "promoted" benefits? Part II of this series reveals responses from a survey of some 3,000 executives about the importance of qualitative and quantitative benefits in the "buying process."

Revised Olweus Bully/Victim Questionnaire: evaluation in visually impaired.

PubMed

Gothwal, Vijaya K; Sumalini, Rebecca; Irfan, Shaik Mohammad; Giridhar, Avula; Bharani, Seelam

2013-08-01

To explore the psychometric properties of the revised Olweus Bully/Victim Questionnaire (OBVQ) in children with visual impairment (VI) using Rasch analysis. One hundred fifty Indian children with VI between 8 and 16 years (mean age, 11.6 years; 69% male; mean acuity in the better eye of 0.80 logMAR [Snellen, 20/126]) were administered the revised OBVQ. The 40-item revised OBVQ was developed to assess victimization (i.e., being bullied) and bullying (bullying others) in normally sighted schoolchildren. Only 16 items are used for Rasch analysis and are divided into two parts: I (victimization, eight items) and II (bullying others, eight items). Separate Rasch analysis was conducted for both parts, and the psychometric properties investigated included behavior of rating scale, extent to which the items measured a single construct (unidimensionality by fit statistics and principal component analysis [PCA] of residuals); ability to discriminate among participants' victimization and bullying behaviors (measurement precision as assessed by person separation reliability [PSR] minimum recommended value, 0.80); and targeting of items to participants' victimization and bullying. Response categories were misused for both parts I and II, which required repair before further analysis. Measurement precision was inadequate for both parts (PSR, 0.64 for part I and 0.19 for part II), indicating poor discriminatory ability. All items fit the Rasch model well in part I, indicating unidimensionality that was further confirmed using PCA of residuals. However, an item misfit in part II that required deletion following which the remaining items fit and PCA of residuals also supported unidimensionality. Targeting was -0.58 logits for part I, indicating that the items were matched well with the participants' victimization. By comparison, targeting was suboptimal for part II (-1.97 logits). In its current state, the revised OBVQ is not a valid psychometric instrument to assess victimization and bullying among children with VI.

AUTOMOTIVE DIESEL MAINTENANCE L. UNIT XII, PART I--MAINTAINING THE FUEL SYSTEM (PART II), CUMMINS DIESEL ENGINE, PART II--UNIT INSTALLATION (ENGINE).

ERIC Educational Resources Information Center

Human Engineering Inst., Cleveland, OH.

THIS MODULE OF A 30-MODULE COURSE IS DESIGNED TO DEVELOP AN UNDERSTANDING OF THE OPERATION AND MAINTENANCE OF THE DIESEL ENGINE FUEL SYSTEM AND THE PROCEDURES FOR DIESEL ENGINE INSTALLATION. TOPICS ARE FUEL FLOW CHARACTERISTICS, PTG FUEL PUMP, PREPARATION FOR INSTALLATION, AND INSTALLING ENGINE. THE MODULE CONSISTS OF A SELF-INSTRUCTIONAL BRANCH…

Literacy and Deaf Students in Taiwan: Issues, Practices and Directions for Future Research--Part II

ERIC Educational Resources Information Center

Liu, Hsiu Tan; Andrews, Jean F.; Liu, Chun Jung

2014-01-01

In Part I, we underscore the issues surrounding young deaf and hard of hearing (DHH) learners of literacy in Taiwan who use sign to support their learning of Chinese literacy. We also described the linguistic features of Chinese writing and the visual codes used by DHH children. In Part II, we describe the reading and writing practices used with…

48 CFR 3415.406-3 - Part II-Contract clauses.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Part II-Contract clauses. 3415.406-3 Section 3415.406-3 Federal Acquisition Regulations System DEPARTMENT OF EDUCATION ACQUISITION REGULATION CONTRACTING METHODS AND CONTRACT TYPES CONTRACTING BY NEGOTIATION Solicitation and...

Matematicas Para El Primer Ciclo Secundario, Volumen II (Parte 1). Traduccion Preliminar de la Edicion en Ingles Revisada. (Mathematics for Junior High School, Volume II, Part 1. Preliminary Translation of the Revised English Edition).

ERIC Educational Resources Information Center

Anderson, R. D.; And Others

This is part one of a two-part SMSG mathematics text for junior high school students. Key ideas emphasized are structure of arithmetic from an algebraic viewpoint, the real number system as a progressing development, and metric and non-metric relations in geometry. Chapter topics include number line and coordinates, equations, scientific notation,…

Part I: Steady States in Two-Species Particle Aggregation. Part II: Sparse Representations for Multiscale PDE

DTIC Science & Technology

2015-03-01

University of California Los Angeles Part I: Steady States in Two-Species Particle Aggregation Part II: Sparse Representations for Multiscale PDE A ...Highway, Suite 1204, Arlington VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to a ...penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. 1. REPORT DATE MAR 2015

Physiotherapy versus placebo or no intervention in Parkinson's disease.

PubMed

Tomlinson, Claire L; Patel, Smitaa; Meek, Charmaine; Clarke, Carl E; Stowe, Rebecca; Shah, Laila; Sackley, Catherine M; Deane, Katherine H O; Herd, Clare P; Wheatley, Keith; Ives, Natalie

2012-07-11

Despite medical therapies and surgical interventions for Parkinson's disease (PD), patients develop progressive disability. The role of physiotherapy aims to maximise functional ability and minimise secondary complications through movement rehabilitation within a context of education and support for the whole person. The overall aim is to optimise independence, safety and well-being, thereby enhancing quality of life. To assess the effectiveness of physiotherapy intervention compared with no intervention in patients with PD. We identified relevant trials by electronic searches of numerous literature databases (e.g. MEDLINE, EMBASE) and trial registers, plus handsearching of major journals, abstract books, conference proceedings and reference lists of retrieved publications. The literature search included trials published up to end of December 2010. Randomised controlled trials of physiotherapy intervention versus no physiotherapy intervention in patients with PD. Two review authors independently extracted data from each article. We used standard meta-analysis methods to assess the effectiveness of physiotherapy intervention compared with no physiotherapy intervention. Trials were classified into the following intervention comparisons: general physiotherapy, exercise, treadmill training, cueing, dance and martial arts. We used tests for heterogeneity to assess for differences in treatment effect across these different physiotherapy interventions. We identified 33 trials with 1518 participants. Compared with no-intervention, physiotherapy significantly improved the gait outcomes of velocity (mean difference 0.05 m/s, 95% confidence interval (CI): 0.02 to 0.07, P = 0.0002), two- or six-minute walk test (16.40 m, CI: 1.90 to 30.90, P = 0.03) and step length (0.03 m, CI: 0 to 0.06, P = 0.04); functional mobility and balance outcomes of Timed Up & Go test (-0.61 s, CI: -1.06 to -0.17, P = 0.006), Functional Reach Test (2.16 cm, CI: 0.89 to 3.43, P = 0.0008) and Berg Balance Scale (3.36 points, CI: 1.91 to 4.81, P < 0.00001); and clinician-rated disability using the Unified Parkinson's Disease Rating Scale (UPDRS) (total: -4.46 points, CI -7.16 to -1.75, P = 0.001; activities of daily living: -1.36, CI -2.41 to -0.30, P = 0.01; and motor: -4.09, CI: -5.59 to -2.59, P < 0.00001). There was no difference between arms in falls or patient-rated quality of life. Indirect comparisons of the different physiotherapy interventions found no evidence that the treatment effect differed across the physiotherapy interventions for any of the outcomes assessed. Benefit for physiotherapy was found in most outcomes over the short-term (i.e. < three months), but was only significant for velocity, two- or six-minute walk test, step length, Timed Up & Go, Functional Reach Test, Berg Balance Scale and clinician-rated UPDRS. Most of the observed differences between the treatments were small. However, for some outcomes (e.g. velocity, Berg Balance Scale and UPDRS), the differences observed were at, or approaching, what are considered minimally clinical important changes.The review illustrates that a wide range of approaches are employed by physiotherapists to treat PD. However, there was no evidence of differences in treatment effect between the different types of physiotherapy interventions being used, though this was based on indirect comparisons. There is a need to develop a consensus menu of 'best-practice' physiotherapy, and to perform large well-designed randomised controlled trials to demonstrate the longer-term efficacy and cost-effectiveness of 'best practice' physiotherapy in PD.

Expression of vesicular glutamate transporters, VGluT1 and VGluT2, in axon terminals of nociceptive primary afferent fibers in the superficial layers of the medullary and spinal dorsal horns of the rat.

PubMed

Li, Jin-Lian; Fujiyama, Fumino; Kaneko, Takeshi; Mizuno, Noboru

2003-03-10

We examined immunohistochemically whether the vesicular glutamate transporters (VGluTs), VGluT1 and VGluT2, might be expressed in synaptic terminals of nociceptive primary afferent fibers within laminae I and II of the medullary and spinal dorsal horns of the rat. VGluT1 immunoreactivity (IR) was intense in the inner part of lamina II but weak in lamina I and the outer part of lamina II. VGluT2-IR was most intense in lamina I and the outer part of lamina II. Expression of VGluTs in synaptic terminals was confirmed by dual immunofluorescence histochemistry for VGluTs and synaptophysin. Expression of VGluTs in axon terminals of primary afferent fibers terminating in laminae I and II was also confirmed immunohistochemically after unilateral dorsal rhizotomy. The dual immunofluorescence histochemistry indicated expression of VGluTs in substance P (SP)-containing axon terminals in lamina I and the outer part of lamina II. Electron microscopy confirmed the coexpression of VGluTs and SP in axon terminals within laminae I and II; VGluTs was associated with round synaptic vesicles at the asymmetric synapses. It was further observed that isolectin IB4, a marker for unmyelinated axons, often bound with VGluT2-immunopositive structures but rarely with VGluT1-immunopositive structures in lamina II. Thus, the results indicated in laminae I and II of the medullary and spinal dorsal horns that both VGluT1 and VGluT2 were expressed in axon terminals of primary afferent fibers, including SP-containing nociceptive fibers and that VGluT in unmyelinated primary afferent fibers terminating in lamina II was primarily VGluT2. Copyright 2003 Wiley-Liss, Inc.

PACE. A Program for Acquiring Competence in Entrepreneurship. Part II: Becoming an Entrepreneur. Unit G: Resources for Managerial Assistance. Research and Development Series No. 194 B-7.

ERIC Educational Resources Information Center

Ohio State Univ., Columbus. National Center for Research in Vocational Education.

This three-part curriculum for entrepreneurship education is primarily for postsecondary level, including four-year colleges and adult education, but it can be adapted for special groups or vocational teacher education. The emphasis of the seven instructional units in Part II is establishing business. Unit G focuses on obtaining managerial…

Final Report for Dynamic Models for Causal Analysis of Panel Data. Models for Change in Quantitative Variables, Part II Scholastic Models. Part II, Chapter 4.

ERIC Educational Resources Information Center

Hannan, Michael T.

This document is part of a series of chapters described in SO 011 759. Stochastic models for the sociological analysis of change and the change process in quantitative variables are presented. The author lays groundwork for the statistical treatment of simple stochastic differential equations (SDEs) and discusses some of the continuities of…

Innovative Culture, Part 2: Virtual Consultancies - Engaging Talent

DTIC Science & Technology

2016-01-21

Innovative Culture, Part II: Virtual Consultancies – Engaging Talent January 21, 2016 These are the final briefing slides as approved by...Engaging Talent (Innovative Culture, Part II) – Aims to facilitate and capitalize on the vast capacity for internal consultancy within the DoD...for talent with an industry model that values – and makes effective use of – young, fresh, innovative voices  With a huge uniformed workforce

PACE. A Program for Acquiring Competence in Entrepreneurship. Part II: Becoming an Entrepreneur. Unit A: Developing the Business Plan. Research and Development Series No. 194 B-1.

ERIC Educational Resources Information Center

Ohio State Univ., Columbus. National Center for Research in Vocational Education.

This three-part curriculum for entrepreneurship education is primarily for postsecondary level, including four-year colleges and adult education, but it can be adapted for special groups or vocational teacher education. The emphasis of the seven instructional units in Part II is establishing a business. Unit A focuses on developing a business…

40 CFR 52.1078 - Extensions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... second generation On-board Diagnostics (OBD-II) equipped motor vehicles as part of its inspection and...-II checks (for 1996-and-newer OBD-II equipped vehicles) as an element of the Commonwealth's I/M...

Student Performance on the NBME Part II Subtest and Subject Examination in Obstetrics-Gynecology.

ERIC Educational Resources Information Center

Metheny, William P.; Holzman, Gerald B.

1988-01-01

Comparison of the scores of 342 third-year medical students on the National Board of Medical Examiners subject examination and the Part II subtest on obstetrics-gynecology found significantly better performance on the former, suggesting a need to interpret the scores differently. (Author/MSE)

Analysis of Vietnamization: Summary and Evaluation

DTIC Science & Technology

1973-11-01

Ellsberg, Daniel . Some Lessons from Failure in Vietnam, P-4036. Santa Monica: The RAND Corp., July 1969. Fulbright, J. William (ed.). The Vietnam...34 Chira and North Vietnam: Two Revolutionary Paths, " Part I, Current Scene, Vol. IX, No. II (Nov 7, 1971), Part II, Current Scene. Vol. IX, No. IZ (Doc 7

26 CFR 1.856-2 - Limitations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... TAXES Real Estate Investment Trusts § 1.856-2 Limitations. (a) Effective date. The provisions of part II... estate investment trust beginning after December 31, 1960. (b) Election. Under the provisions of section 856(c)(1), a trust, even though it satisfies the other requirements of part II of subchapter M for the...

Department of Defense Index of Specifications and Standards. Part 1. Alphabetical Listing

DTIC Science & Technology

1989-07-01

the Basic DODISS Part II. PART II, Numerical Listing reflects all active documents in document number sequence within document type. The alphabetic...NPFC 106) 5801 Tabor Avenue P ’ - elphia, PA 19120 "The use Index is mandatory on all military activities . This mandatory provision i as thiat the...Class, is also available as follows: Military Activities : Commanding Officer Naval Publications and Forms Center (ATTN: NPODS) 5801 Tabor Avenue

Nursing Care of Patients Undergoing Chemotherapy Desensitization: Part II.

PubMed

Jakel, Patricia; Carsten, Cynthia; Carino, Arvie; Braskett, Melinda

2016-04-01

Chemotherapy desensitization protocols are safe, but labor-intensive, processes that allow patients with cancer to receive medications even if they initially experienced severe hypersensitivity reactions. Part I of this column discussed the pathophysiology of hypersensitivity reactions and described the development of desensitization protocols in oncology settings. Part II incorporates the experiences of an academic medical center and provides a practical guide for the nursing care of patients undergoing chemotherapy desensitization.
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PACE. A Program for Acquiring Competence in Entrepreneurship. Part II: Becoming an Entrepreneur. Unit E: Choosing the Type of Ownership. Research and Development Series No. 194 B-5.

ERIC Educational Resources Information Center

Ohio State Univ., Columbus. National Center for Research in Vocational Education.

This three-part curriculum for entrepreneurship education is primarily for postsecondary level, including four-year colleges and adult education, but it can be adapted for special groups or vocational teacher education. The emphasis of the seven instructional units in Part II is establishing a business. Unit E focuses on the three major types of…

Bases of Classification of Geometric Concepts Used by Children of Varying Characteristics. Report from the Project on Situational Variables and Efficiency of Concept Learning. Part II.

ERIC Educational Resources Information Center

Wiviott, Suzanne Pasch

This document, Part II of a two-part study, is the summary chapter of a report which sought to ascertain the relationship of grade level, achievement level, sex, and method of presentation to the various bases by which children classify geometric concepts. Two tasks, administered consecutively to 96 subjects in grades five, eight, and eleven,…

Starting a hospital-based home health agency: Part II--Key success factors.

PubMed

Montgomery, P

1993-09-01

In Part II of a three-part series, the financial, technological and legislative issues of a hospital-based home health-agency are discussed. Beginning a home healthcare service requires intensive research to answer key environmental and operational questions--need, competition, financial projections, initial start-up costs and the impact of delayed depreciation. Assessments involving technology, staffing, legislative and regulatory issues can help project service volume, productivity and cost-control.

PACE. A Program for Acquiring Competence in Entrepreneurship. Part II: Becoming an Entrepreneur. Unit F: How to Finance the Business. Research and Development Series No. 194 B-6.

ERIC Educational Resources Information Center

Ohio State Univ., Columbus. National Center for Research in Vocational Education.

This three-part curriculum for entrepreneurship education is primarily for postsecondary level, including four-year colleges and adult education, but it can be adapted for special groups or vocational teacher education. The emphasis of the seven instructional units in Part II is establishing a business. Unit F focuses on financing the business. It…

PACE. A Program for Acquiring Competence in Entrepreneurship. Part II: Becoming an Entrepreneur. Unit B: Where to Locate the Business. Research and Development Series No. 194 B-2.

ERIC Educational Resources Information Center

Ohio State Univ., Columbus. National Center for Research in Vocational Education.

This three-part curriculum for entrepreneurship education is primarily for postsecondary level, including four-year colleges and adult education, but it can be adapted for special groups or vocational teacher education. The emphasis of the seven instructional units in Part II is on establishing a business. Unit B focuses on choosing a business…

PACE. A Program for Acquiring Competence in Entrepreneurship. Part II: Becoming an Entrepreneur. Unit D: Government Regulations and Small Businesses. Research and Development Series No. 194 B-4.

ERIC Educational Resources Information Center

Ohio State Univ., Columbus. National Center for Research in Vocational Education.

This three-part curriculum for entrepreneurship education is primarily for postsecondary level, including four-year colleges and adult education, but it can be adapted for special groups or vocational teacher education. The emphasis of the seven instructional units in Part II is establishing a business. Unit D focuses on business regulations at…

PACE. A Program for Acquiring Competence in Entrepreneurship. Part II: Becoming an Entrepreneur. Unit C: Legal Issues and Small Business. Research and Development Series No. 194 B-3.

ERIC Educational Resources Information Center

Ohio State Univ., Columbus. National Center for Research in Vocational Education.

This three-part curriculum for entrepreneurship education is primarily for postsecondary level, including four-year colleges and adult education, but it can be adapted for special groups or vocational teacher education. The emphasis of the seven instructional units in Part II is establishing a business. Unit C focuses on legal issues that affect…