Parkinson’s Disease The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. Complexity Analysis of Electroencephalogram Dynamics in Patients with Parkinson’s Disease Mon, 20 Feb 2017 00:00:00 +0000 In this study, a new combination scheme has been proposed for detecting Parkinson’s disease (PD) from electroencephalogram (EEG) signal recorded from normal subjects and PD patients. The scheme is based on discrete wavelet transform (DWT), sample entropy (SampEn), and the three-way decision model in analysis of EEG signal. The EEG signal is noisy and nonstationary, and, as a consequence, it becomes difficult to distinguish it visually. However, the scheme is a well-established methodology in analysis of EEG signal in three stages. In the first stage, the DWT was applied to acquire the split frequency information; here, we use three-level DWT to decompose EEG signal into approximation and detail coefficients; in this stage, we aim to remove the useless and noise information and acquire the effective information. In the second stage, as the SampEn has advantage in analyzing the EEG signal, we use the approximation coefficient to compute the SampEn values. Finally, we detect the PD patients using three-way decision based on optimal center constructive covering algorithm (O_CCA) with the accuracy about 92.86%. Without DWT as preprocessing step, the detection rate reduces to 88.10%. Overall, the combination scheme we proposed is suitable and efficient in analyzing the EEG signal with higher accuracy. Guotao Liu, Yanping Zhang, Zhenghui Hu, Xiuquan Du, Wanqing Wu, Chenchu Xu, Xiangyang Wang, and Shuo Li Copyright © 2017 Guotao Liu et al. All rights reserved. Association of Gait Characteristics and Depression in Patients with Parkinson’s Disease Assessed in Goal-Directed Locomotion Task Wed, 15 Feb 2017 00:00:00 +0000 Introduction. In the genesis of Parkinson’s disease (PD) clinical phenomenology the exact nature of the association between bradykinesia and affective variables is unclear. In the present study, we analyzed the gait characteristics and level of depression in PD and healthy volunteers. Methods. Patients with PD () and healthy controls () were recruited for the present study. Walking speed, stride length, and cadence were compared between groups while participants completed a goal-directed locomotion task under visually controlled (VC) and visually noncontrolled conditions (VnC). Results. Significantly higher depression scores were found in PD comparing to healthy control groups. In PD, depression was associated with gait components in the VC wherein the place of the target was visible. In contrast, in healthy subjects the depression was associated with gait components in VnC wherein the location and image of the target were memorized and recalled. In patients with PD and depression, the visually deprived multitask augments the rate of cadence and diminishes stride length, while velocity remains relatively unchanged. The depression associated with gait characteristics as a comorbid affective factor in PD, and that impairs the coherence of gait pattern. Conclusion. The relationship between depression and gait parameters appears to indicate that PD not only is a neurological disease but also incorporates affective disturbances that associate with the regulation of gait characteristics. Péter Kincses, Norbert Kovács, Kázmér Karádi, Ádám Feldmann, Krisztina Dorn, Zsuzsanna Aschermann, Sámuel Komoly, Tibor Szolcsányi, Árpád Csathó, and János Kállai Copyright © 2017 Péter Kincses et al. All rights reserved. Determinants of Dyadic Relationship and Its Psychosocial Impact in Patients with Parkinson’s Disease and Their Spouses Tue, 14 Feb 2017 00:00:00 +0000 The caregiver-care receiver relationship (mutuality) in Parkinson’s disease (PD) and its association with motor and non-motors symptoms, health-related quality of life (HRQoL), and caregiver burden have not fully been investigated. The aim of our study was to explore if (1) the level of mutuality perceived by PD-patients and PD-partners differs, (2) different factors are associated with perceived mutuality by PD-patients and PD-partners, and (3) mutuality is associated with PD-patients health-related quality of life (HRQoL) and caregiver burden. We collected data on motor signs (UPDRS III), non-motor manifestations (NMSQuest), PD-patients’ cognition (IQCODE), mutuality scale (MS), PD-patients’ HRQoL (PDQ8), and caregiver burden (CB) from 51 PD dyads. Predictors were identified using multivariate regression analyses. Overall, the dyads rated their own mutuality as high with no significant difference between the dyads except for the dimension of reciprocity. PD-patients’ MS score () and NMSQuest ( ≤ .001) were significant predictors of PDQ8. Strongest predictor of CB was PD-partners’ MS score (<.001) and IQCODE (). In general, it seems that non-motor symptoms contribute to a larger extent to the mutual relationship in PD-affected dyads than motor disabilities. Michaela Karlstedt, Seyed-Mohammad Fereshtehnejad, Dag Aarsland, and Johan Lökk Copyright © 2017 Michaela Karlstedt et al. All rights reserved. Meta-Analysis of the Relationship between Deep Brain Stimulation in Patients with Parkinson’s Disease and Performance in Evaluation Tests for Executive Brain Functions Wed, 08 Feb 2017 00:00:00 +0000 Parkinson’s disease (PD) is a neurodegenerative condition, which compromises the motor functions and causes the alteration of some executive brain functions. The presence of changes in cognitive symptoms in PD could be due to the procedure of deep brain stimulation (DBS). We searched in several databases for studies that compared performance in executive function tests before and after the DBS procedure in PE and then performed a meta-analysis. After the initial search, there were 15 articles that specifically evaluated the functions of verbal fluency, working memory, cognitive flexibility, abstract thinking, and inhibition. It was found that there were differences in the evaluation of the cognitive functions in terms of the protocols, which generated heterogeneity in the results of the meta-analysis. Likewise, a tendency to diminish functions like verbal fluency and inhibition was found, being this consistent with similar studies. In the other functions evaluated, no difference was found between pre- and postsurgery scores. Monitoring of this type of function is recommended after the procedure. A. M. Martínez-Martínez, O. M. Aguilar, and C. A. Acevedo-Triana Copyright © 2017 A. M. Martínez-Martínez et al. All rights reserved. Twice-Daily versus Once-Daily Pramipexole Extended Release Dosage Regimens in Parkinson’s Disease Tue, 07 Feb 2017 08:38:05 +0000 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 Ji Young Yun, Young Eun Kim, Hui-Jun Yang, Han-Joon Kim, and Beomseok Jeon Copyright © 2017 Ji Young Yun et al. All rights reserved. LSVT-BIG Improves UPDRS III Scores at 4 Weeks in Parkinson’s Disease Patients with Wearing Off: A Prospective, Open-Label Study Wed, 01 Feb 2017 09:37:18 +0000 The efficacy of LSVT-BIG for advanced Parkinson’s disease (PD) patients with wearing off remains to be determined. Therefore, we evaluated whether LSVT-BIG improves motor disability in eight PD patients with wearing off. Unified Parkinson’s Disease Rating Scale (UPDRS) scores, daily off time, and mobility assessments were evaluated during the “on” time before and after the LSVT-BIG course. LSVT-BIG significantly improved UPDRS III scores at 4 weeks and UPDRS II scores in the “off” state at 12 weeks, with no changes in the other measures. The findings suggest that LSVT-BIG may be an effective therapy for advanced PD patients with wearing off. Tatsuya Ueno, Megumi Sasaki, Haruo Nishijima, Yukihisa Funamizu, Tomoya Kon, Rie Haga, Akira Arai, Chieko Suzuki, Jin-ichi Nunomura, Masayuki Baba, and Masahiko Tomiyama Copyright © 2017 Tatsuya Ueno et al. All rights reserved. Identification of NURR1 (Exon 4) and FOXA1 (Exon 3) Haplotypes Associated with mRNA Expression Levels in Peripheral Blood Lymphocytes of Parkinson’s Patients in Small Indian Population Tue, 31 Jan 2017 00:00:00 +0000 Here, we study the expression of NURR1 and FOXA1 mRNA in peripheral blood lymphocytes and its haplotypes in coding region in a small Chennai population of India. Thirty cases of Parkinson’s patients (PD) with anti-PD medications (20 males aged and 10 females aged ) and 30 age matched healthy people (20 males aged and 10 females aged ) were included. The expression of NURR1 and FOXA1 in PBL was detected by Q-PCR and haplotypes were identified by PCR-SSCP. In the 30 PD cases examined, NURR1 and FOXA1 expression was significantly reduced in both male and female PD patients. However, NURR1 (57.631% reduced in males; 28.93% in females) and FOXA1 (64.42% in males; 55.76% in females) mRNA expression did differ greatly between male and female PD patients. Polymorphisms were identified at exon 4 of the NURR1 and at exon 3 of the FOXA1, respectively, in both male and female patients. A near significant difference in SSCP patterns between genders of control and PD population was analyzed suggesting that further investigations of more patients, more molecular markers, and coding regions should be performed. Such studies could potentially reveal peripheral molecular marker of early PD and different significance to the respective genders. Jayakrishna Tippabathani, Jayshree Nellore, Vaishnavie Radhakrishnan, Somashree Banik, and Sonia Kapoor Copyright © 2017 Jayakrishna Tippabathani et al. All rights reserved. Impact of Combined Subthalamic Nucleus and Substantia Nigra Stimulation on Neuropsychiatric Symptoms in Parkinson’s Disease Patients Thu, 26 Jan 2017 09:29:23 +0000 The goal of the study was to compare the tolerability and the effects of conventional subthalamic nucleus (STN) and combined subthalamic nucleus and substantia nigra (STN+SNr) high-frequency stimulation in regard to neuropsychiatric symptoms in Parkinson’s disease patients. In this single center, randomized, double-blind, cross-over clinical trial, twelve patients with advanced Parkinson’s disease (1 female; age: years; disease duration: years; Hoehn and Yahr stage: ) were included. Apathy, fatigue, depression, and impulse control disorder were assessed using a comprehensive set of standardized rating scales and questionnaires such as the Lille Apathy Rating Scale (LARS), Modified Fatigue Impact Scale (MFIS), Becks Depression Inventory (BDI-I), Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease Rating Scale (QUIP-RS), and Parkinson’s Disease Questionnaire (PDQ-39). Three patients that were initially assigned to the STN+SNr stimulation mode withdrew from the study within the first week due to discomfort. Statistical comparison of data retrieved from patients who completed the study revealed no significant differences between both stimulation conditions in terms of mean scores of scales measuring apathy, fatigue, depression, impulse control disorder, and quality of life. Individual cases showed an improvement of apathy under combined STN+SNr stimulation. In general, combined STN+SNr stimulation seems to be safe in terms of neuropsychiatric side effects, although careful patient selection and monitoring in the short-term period after changing stimulation settings are recommended. U. Hidding, A. Gulberti, A. Horn, C. Buhmann, W. Hamel, J. A. Koeppen, M. Westphal, A. K. Engel, C. Gerloff, D. Weiss, C. K. E. Moll, and M. Pötter-Nerger Copyright © 2017 U. Hidding et al. All rights reserved. Stigma Experienced by Parkinson’s Disease Patients: A Descriptive Review of Qualitative Studies Tue, 24 Jan 2017 13:16:19 +0000 Parkinson’s disease (PD) is a neurodegenerative disease characterized by motor and nonmotor symptoms. Both of them imply a negative impact on Health-Related Quality of Life. A significant one is the stigma experienced by the parkinsonian patients and their caregivers. Moreover, stigma may affect everyday life and patient’s subjective and relational perception and it may lead to frustration and isolation. Aim of the present work is to qualitatively describe the stigma of PD patients stemming from literature review, in order to catch the subjective experience and the meaning of the stigma construct. Literature review was performed on PubMed database and Google Scholar (keywords: Parkinson Disease, qualitative, stigma, social problem, isolation, discrimination) and was restricted to qualitative data: 14 articles were identified to be suitable to the aim of the present overview. Results are divided into four core constructs: stigma arising from symptoms, stigma linked to relational and communication problems, social stigma arising from sharing perceptions, and caregiver’s stigma. The principal relations to these constructs are deeply analyzed and described subjectively through patients’ and caregiver’s point of view. The qualitative research may allow a better understanding of a subjective symptom such as stigma in parkinsonian patients from an intercultural and a social point of view. Marina Maffoni, Anna Giardini, Antonia Pierobon, Davide Ferrazzoli, and Giuseppe Frazzitta Copyright © 2017 Marina Maffoni et al. All rights reserved. Mutation Analysis of HTRA2 Gene in Chinese Familial Essential Tremor and Familial Parkinson’s Disease Tue, 24 Jan 2017 00:00:00 +0000 Background. HTRA2 has already been nominated as PARK13 which may cause Parkinson’s disease, though there are still discrepancies among these results. Recently, Gulsuner et al.’s study found that HTRA2 p.G399S is responsible for hereditary essential tremor and homozygotes of this allele develop Parkinson’s disease by examining a six-generation family segregating essential tremor and essential tremor coexisting with Parkinson’s disease. We performed this study to validate the condition of HTRA2 gene in Chinese familial essential tremor and familial Parkinson’s disease patients, especially essential tremor. Methods. We directly sequenced all eight exons, exon-intron boundaries, and part of the introns in 101 familial essential tremor patients, 105 familial Parkinson’s disease patients, and 100 healthy controls. Results. No exonic variant was identified, while one exon-intron boundary variant (rs2241028) and one intron variant (rs2241027) were detected, both with no clinical significance and uncertain function. There was no difference in allele, genotype, and haplotype between groups. Conclusions. HTRA2 exonic variant might be rare among Chinese Parkinson’s disease and essential tremor patients with family history, and HTRA2 may not be the cause of familial Parkinson’s disease and essential tremor in China. Ya-Chao He, Pei Huang, Qiong-Qiong Li, Qian Sun, Dun-Hui Li, Tian Wang, Jun-Yi Shen, Juan-Juan Du, Shi-Shuang Cui, Chao Gao, Rao Fu, and Sheng-Di Chen Copyright © 2017 Ya-Chao He et al. All rights reserved. Consensus on the Definition of Advanced Parkinson’s Disease: A Neurologists-Based Delphi Study (CEPA Study) Mon, 23 Jan 2017 00:00:00 +0000 To date, no consensus exists on the key factors for diagnosing advanced Parkinson disease (APD). To obtain consensus on the definition of APD, we performed a prospective, multicenter, Spanish nationwide, 3-round Delphi study (CEPA study). An ad hoc questionnaire was designed with 33 questions concerning the relevance of several clinical features for APD diagnosis. In the first-round, 240 neurologists of the Spanish Movement Disorders Group participated in the study. The results obtained were incorporated into the questionnaire and both, results and questionnaire, were sent out to and fulfilled by 26 experts in Movement Disorders. Review of results from the second-round led to a classification of symptoms as indicative of “definitive,” “probable,” and “possible” APD. This classification was confirmed by 149 previous participating neurologists in a third-round, where 92% completely or very much agreed with the classification. Definitive symptoms of APD included disability requiring help for the activities of daily living, presence of motor fluctuations with limitations to perform basic activities of daily living without help, severe dysphagia, recurrent falls, and dementia. These results will help neurologists to identify some key factors in APD diagnosis, thus allowing users to categorize the patients for a homogeneous recognition of this condition. Maria-Rosario Luquin, Jaime Kulisevsky, Pablo Martinez-Martin, Pablo Mir, and Eduardo S. Tolosa Copyright © 2017 Maria-Rosario Luquin et al. All rights reserved. Benefit from the Chin-Down Maneuver in the Swallowing Performance and Self-Perception of Parkinson’s Disease Patients Thu, 19 Jan 2017 14:24:02 +0000 Aims. To verify the effectiveness of the maneuver application in swallowing therapy with PD. Materials and Method. We performed an open-label trial, with three groups compounds by PD individuals: the experimental group, control group, and orientation group. The study included PD patients with dysphagia. A cognitive screening, through a questionnaire about depression and quality of life, was conducted. Swallowing assessment was performed through (1) fiberoptic endoscopic evaluation of swallowing (FEES); (2) clinical evaluation and Functional Oral Intake Scale (FOIS); and (3) assessment of the quality life related to swallowing (SWALQOL). A therapeutic program, which consisted of chin-down postural maneuver and orientations on feeding, was applied. Both groups (EG and OG) received on-month therapeutic program. Results. A significant improvement in swallowing, evaluated by clinical assessment, was observed in solid () and liquid () consistencies in EG when compared to OG and CG. Patients in EG presented improvement in QoL, with the significant difference in comparison with the other groups, about domain frequency of symptoms () in SWALQOL questionnaire. Conclusion. The postural maneuver chin-down improved swallowing performance and self-perception, but not the laryngeal signs. This trial is registered with registration number NCT02973698. Annelise Ayres, Geraldo Pereira Jotz, Carlos R. M. Rieder, and Maira Rozenfeld Olchik Copyright © 2017 Annelise Ayres et al. All rights reserved. A Case-Control Association Study of RANTES (-28C>G) Polymorphism as a Risk Factor for Parkinson’s Disease in Isparta, Turkey Sun, 18 Dec 2016 14:19:04 +0000 Background. Recent studies have revealed that inflammatory processes are involved in the pathogenesis of Parkinson’s disease (PD). Multiple lines of evidence have suggested that chemokines and their receptors are involved in several neurodegenerative disorders. We have examined whether genetic polymorphisms at the genes encoding chemokines IL-8 (-251A>T), MCP-1 (-2518A/G), and RANTES (-28C>G) and chemokine receptors CCR2 (V64I) and CCR5 (-Δ32) were associated with sporadic PD risk in Isparta, Turkey. Method. The pilot case-control association study included 30 PD patients and 60 control subjects, who were all genotyped with PCR-RFLP for the five polymorphisms. Their genotype and haplotype frequencies were compared statistically. Results. One SNP (-28C>G) in RANTES revealed a significant association with PD (P (allele) < 0.0001, p-trend = 0.0007). The risk allele (G) in the homozygous and dominant models (OR = 17.29 and 32.10, 95% CI = 0.86–347.24 and 1.74–591.937, resp.) suggests additional PD risk. The haplotype TGCAN from the IL-8 (-251A>T), MCP-1 (-2518A>G), RANTES (-28C>G), CCR-2 (V64I), and CCR-5 (-Δ32) has protective effect (OR = 0.08 [CI = 0.01–0.63], ). Conclusions. Our data are the first indication of the role of RANTES (-28C>G) in PD risk. Nilufer Sahin-Calapoglu, Serpil Demirci, Mustafa Calapoglu, and Baris Yasar Copyright © 2016 Nilufer Sahin-Calapoglu et al. All rights reserved. Ophthalmologic Baseline Characteristics and 2-Year Ophthalmologic Safety Profile of Pramipexole IR Compared with Ropinirole IR in Patients with Early Parkinson’s Disease Sun, 18 Dec 2016 11:07:41 +0000 Background. Parkinson’s disease (PD) progressively affects dopaminergic neurotransmission and may affect retinal dopaminergic functions and structures. Objective. This 2-year randomized, open-label, parallel-group, flexible-dose study, NCT00144300, evaluated ophthalmologic safety profiles of immediate-release (IR) pramipexole and ropinirole in patients with early idiopathic PD with ≤6 months’ prior dopamine agonist exposure and without preexisting major eye disorders. Methods. Patients received labeled IR regimens of pramipexole () or ropinirole () for 2 years. Comprehensive ophthalmologic assessments (COA) included corrected acuity, Roth 28-color test, slit-lamp biomicroscopy, intraocular pressure, computerized visual field test, fundus photography, and electroretinography. Results. At baseline, we observed retinal pigmentary epithelium (RPE) hypopigmentation not previously reported in PD patients. The estimated relative risk of 2-year COA worsening with pramipexole versus ropinirole was 1.07 (95% CI: 0.71–1.60). Mean changes from baseline in Unified Parkinson’s Disease Rating System parts II+III total scores (pramipexole: 1 year, −, and 2 years, −, and ropinirole: 1 year, −, and 2 years, −) and Hoehn–Yahr stage distribution showed therapeutic effects on PD symptoms. Safety profiles were consistent with labeling. Conclusions. The risk of retinal deterioration did not differ in early idiopathic PD patients receiving pramipexole versus ropinirole. RPE hypopigmentation at baseline was not previously reported in this population. This trial is registered with NCT00144300. William Seiple, Danna Jennings, Richard B. Rosen, Leona Borchert, Lee Canale, Nora Fagan, and Mark Forrest Gordon Copyright © 2016 William Seiple et al. All rights reserved. Parkinson’s Disease and Cognitive Impairment Mon, 12 Dec 2016 12:44:43 +0000 Parkinson’s disease (PD) is a progressive neurodegenerative disease primarily characterized by the hallmarks of motor symptoms, such as tremor, bradykinesia, rigidity, and postural instability. However, through clinical investigations in patients and experimental findings in animal models of Parkinson’s disease for years, it is now well recognized that Parkinson’s disease is more than just a motor-deficit disorder. The majority of Parkinson’s disease patients suffer from nonmotor disabilities, for instance, cognitive impairment, autonomic dysfunction, sensory dysfunction, and sleep disorder. So far, anti-PD prescriptions and surgical treatments have been mainly focusing on motor dysfunctions, leaving cognitive impairment a marginal clinical field. Within the nonmotor symptoms, cognitive impairment is one of the most common and significant aspects of Parkinson’s disease, and cognitive deficits such as dysexecutive syndrome and visuospatial disturbances could seriously affect the quality of life, reduce life expectancy, prolong the duration of hospitalization, and therefore increase burdens of caregiver and medical costs. In this review, we have done a retrospective study of the recent related researches on epidemiology, clinical manifestation and diagnosis, genetics, and potential treatment of cognitive deficits in Parkinson’s disease, aiming to provide a summary of cognitive impairment in Parkinson’s disease and make it easy for clinicians to tackle this challenging issue in their future practice. Yang Yang, Bei-sha Tang, and Ji-feng Guo Copyright © 2016 Yang Yang et al. All rights reserved. An Integrated Review of Psychological Stress in Parkinson’s Disease: Biological Mechanisms and Symptom and Health Outcomes Mon, 12 Dec 2016 09:13:08 +0000 Parkinson’s disease (PD) is characterized by complex symptoms and medication-induced motor complications that fluctuate in onset, severity, responsiveness to treatment, and disability. The unpredictable and debilitating nature of PD and the inability to halt or slow disease progression may result in psychological stress. Psychological stress may exacerbate biological mechanisms believed to contribute to neuronal loss in PD and lead to poorer symptom and health outcomes. The purpose of this integrated review is to summarize and appraise animal and human research studies focused on biological mechanisms, symptom, and health outcomes of psychological stress in PD. A search of the electronic databases PubMed/Medline and CINAHL from 1980 to the present using the key words Parkinson’s disease and stress, psychological stress, mental stress, and chronic stress resulted in 11 articles that met inclusion criteria. The results revealed significant associations between psychological stress and increased motor symptom severity and loss of dopamine-producing neurons in animal models of PD and between psychological stress and increased symptom severity and poorer health outcomes in human subjects with PD. Further research is needed to fully elucidate the underlying biological mechanisms responsible for these relationships, for the ultimate purpose of designing targeted interventions that may modify the disease trajectory. Kim Wieczorek Austin, Suzanne Weil Ameringer, and Leslie Jameleh Cloud Copyright © 2016 Kim Wieczorek Austin et al. All rights reserved. Event-Related Potentials in Parkinson’s Disease Patients with Visual Hallucination Thu, 08 Dec 2016 11:58:47 +0000 Using neuropsychological investigation and visual event-related potentials (ERPs), we aimed to compare the ERPs and cognitive function of nondemented Parkinson’s disease (PD) patients with and without visual hallucinations (VHs) and of control subjects. We recruited 12 PD patients with VHs (PD-H), 23 PD patients without VHs (PD-NH), and 18 age-matched controls. All subjects underwent comprehensive neuropsychological assessment and visual ERPs measurement. A visual odd-ball paradigm with two different fixed interstimulus intervals (ISI) (1600 ms and 5000 ms) elicited visual ERPs. The frontal test battery was used to assess attention, visual-spatial function, verbal fluency, memory, higher executive function, and motor programming. The PD-H patients had significant cognitive dysfunction in several domains, compared to the PD-NH patients and controls. The mean P3 latency with ISI of 1600 ms in PD-H patients was significantly longer than that in controls. Logistic regression disclosed UPDRS-on score and P3 latency as significant predictors of VH. Our findings suggest that nondemented PD-H patients have worse cognitive function and P3 measurements. The development of VHs in nondemented PD patients might be implicated in executive dysfunction with altered visual information processing. Yang-Pei Chang, Yuan-Han Yang, Chiou-Lian Lai, and Li-Min Liou Copyright © 2016 Yang-Pei Chang et al. All rights reserved. Abdominal Massage for the Relief of Constipation in People with Parkinson’s: A Qualitative Study Thu, 08 Dec 2016 10:23:40 +0000 Objectives. To explore the experiences of people with Parkinson’s (PwP) who suffer from constipation, the impact this has on their lives, and the effect of using lifestyle changes and abdominal massage as a form of constipation management. Method. Fourteen semistructured interviews were completed (8 males and 6 females; mean age 72.2 years) at the end of a care programme, which consisted of either lifestyle advice and abdominal massage (intervention group; ) or lifestyle advice only (control group; ). Data were analysed using constant-comparison techniques and Framework methods. Themes and key quotes were identified to depict major findings. Findings. Four key themes were identified: (i) the adverse impact of bowel problems on quality of life; (ii) positive experience of behaviour adjustments: experimentation; (iii) abdominal massage as a dynamic and relaxing tool: experiential learning (intervention group only); (iv) abdominal massage as a contingency plan: hesitation (control group only). Constipation was reported as having a significant impact on quality of life. Participants in both groups perceived lifestyle advice to relieve symptoms. Specific improvements were described in those who also received the abdominal massage. Conclusions. Both lifestyle advice and abdominal massage were perceived to be beneficial in relieving symptoms of constipation for PwP. D. McClurg, K. Walker, P. Aitchison, K. Jamieson, L. Dickinson, L. Paul, S. Hagen, and A.-L. Cunnington Copyright © 2016 D. McClurg et al. All rights reserved. Gastrointestinal Dysfunctions in Parkinson’s Disease: Symptoms and Treatments Tue, 06 Dec 2016 09:06:30 +0000 A diagnosis of Parkinson’s disease is classically established after the manifestation of motor symptoms such as rigidity, bradykinesia, and tremor. However, a growing body of evidence supports the hypothesis that nonmotor symptoms, especially gastrointestinal dysfunctions, could be considered as early biomarkers since they are ubiquitously found among confirmed patients and occur much earlier than their motor manifestations. According to Braak’s hypothesis, the disease is postulated to originate in the intestine and then spread to the brain via the vagus nerve, a phenomenon that would involve other neuronal types than the well-established dopaminergic population. It has therefore been proposed that peripheral nondopaminergic impairments might precede the alteration of dopaminergic neurons in the central nervous system and, ultimately, the emergence of motor symptoms. Considering the growing interest in the gut-brain axis in Parkinson’s disease, this review aims at providing a comprehensive picture of the multiple gastrointestinal features of the disease, along with the therapeutic approaches used to reduce their burden. Moreover, we highlight the importance of gastrointestinal symptoms with respect to the patients’ responses towards medical treatments and discuss the various possible adverse interactions that can potentially occur, which are still poorly understood. Andrée-Anne Poirier, Benoit Aubé, Mélissa Côté, Nicolas Morin, Thérèse Di Paolo, and Denis Soulet Copyright © 2016 Andrée-Anne Poirier et al. All rights reserved. Marijuana Compounds: A Nonconventional Approach to Parkinson’s Disease Therapy Mon, 05 Dec 2016 13:42:47 +0000 Parkinson’s disease (PD), a neurodegenerative disorder, is the second most common neurological illness in United States. Neurologically, it is characterized by the selective degeneration of a unique population of cells, the nigrostriatal dopamine neurons. The current treatment is symptomatic and mainly involves replacement of dopamine deficiency. This therapy improves only motor symptoms of Parkinson’s disease and is associated with a number of adverse effects including dyskinesia. Therefore, there is unmet need for more comprehensive approach in the management of PD. Cannabis and related compounds have created significant research interest as a promising therapy in neurodegenerative and movement disorders. In this review we examine the potential benefits of medical marijuana and related compounds in the treatment of both motor and nonmotor symptoms as well as in slowing the progression of the disease. The potential for cannabis to enhance the quality of life of Parkinson’s patients is explored. Mariana Babayeva, Haregewein Assefa, Paramita Basu, Sanjeda Chumki, and Zvi Loewy Copyright © 2016 Mariana Babayeva et al. All rights reserved. Deep Brain Stimulation Frequency of the Subthalamic Nucleus Affects Phonemic and Action Fluency in Parkinson’s Disease Mon, 05 Dec 2016 07:46:18 +0000 Introduction. Deep brain stimulation of the subthalamic nucleus (STN-DBS) in Parkinson’s disease (PD) has been linked to a decline in verbal fluency. The decline can be attributed to surgical effects, but the relative contributions of the stimulation parameters are not well understood. This study aimed to investigate the impact of the frequency of STN-DBS on the performance of verbal fluency tasks in patients with PD. Methods. Twenty individuals with PD who received bilateral STN-DBS were evaluated. Their performances of verbal fluency tasks (semantic, phonemic, action, and unconstrained fluencies) upon receiving low-frequency (60 Hz) and high-frequency (130 Hz) STN-DBS were assessed. Results. The performances of phonemic and action fluencies were significantly different between low- and high-frequency STN-DBS. Patients showed a decrease in these verbal fluencies for high-frequency STN-DBS. Conclusion. Low-frequency STN-DBS may be less harmful to the verbal fluency of PD patients. Valéria de Carvalho Fagundes, Carlos R. M. Rieder, Aline Nunes da Cruz, Bárbara Costa Beber, and Mirna Wetters Portuguez Copyright © 2016 Valéria de Carvalho Fagundes et al. All rights reserved. Aerobic Exercise Preserves Olfaction Function in Individuals with Parkinson’s Disease Wed, 23 Nov 2016 12:42:54 +0000 Introduction. Based on anecdotal reports of improved olfaction following aerobic exercise, the aim of this study was to evaluate the effects of an 8-week aerobic exercise program on olfaction function in individuals with Parkinson’s disease (PD). Methods. Thirty-eight participants with idiopathic PD were randomized to either an aerobic exercise group () or a nonexercise control group (). The aerobic exercise group completed a 60-minute cycling session three times per week for eight weeks while the nonexercise control group received no intervention. All participants completed the University of Pennsylvania Smell Identification Test (UPSIT) at baseline, end of treatment, and a four-week follow up. Results. Change in UPSIT scores between the exercise and nonexercise groups from baseline to EOT () and from baseline to EOT+4 () favored the aerobic exercise group. Individuals in the nonexercise group had worsening olfaction function over time, while the exercise group was spared from decline. Discussion. The difference in UPSIT scores suggested that aerobic exercise may be altering central nervous system pathways that regulate the physiologic or cognitive processes controlling olfaction in individuals with PD. While these results provide promising preliminary evidence that exercise may modify the disease process, further systematic evaluation is necessary. Anson B. Rosenfeldt, Tanujit Dey, and Jay L. Alberts Copyright © 2016 Anson B. Rosenfeldt et al. All rights reserved. Blood Plasma of Patients with Parkinson’s Disease Increases Alpha-Synuclein Aggregation and Neurotoxicity Mon, 14 Nov 2016 12:00:55 +0000 A pathological hallmark of Parkinson’s disease (PD) is formation of Lewy bodies in neurons of the brain. This has been attributed to the spread of α-synuclein (α-syn) aggregates, which involves release of α-syn from a neuron and its reuptake by a neighboring neuron. We found that treatment with plasma from PD patients induced more α-syn phosphorylation and oligomerization than plasma from normal subjects (NS). Compared with NS plasma, PD plasma added to primary neuron cultures caused more cell death in the presence of extracellular α-syn. This was supported by the observations that phosphorylated α-syn oligomers entered neurons, rapidly increased accumulated thioflavin S-positive inclusions, and induced a series of metabolic changes that included activation of polo-like kinase 2, inhibition of glucocerebrosidase and protein phosphatase 2A, and reduction of ceramide levels, all of which have been shown to promote α-syn phosphorylation and aggregation. We also analyzed neurotoxicity of α-syn oligomers relative to plasma from different patients. Neurotoxicity was not related to age or gender of the patients. However, neurotoxicity was positively correlated with H&Y staging score. The modification in the plasma may promote spreading of α-syn aggregates via an alternative pathway and accelerate progression of PD. Peng Wang, Xin Li, Xuran Li, Weiwei Yang, and Shun Yu Copyright © 2016 Peng Wang et al. All rights reserved. Median and Ulnar Neuropathy Assessment in Parkinson’s Disease regarding Symptom Severity and Asymmetry Mon, 24 Oct 2016 11:00:23 +0000 Background. While increasing evidence suggests comorbidity of peripheral neuropathy (PNP) and Parkinson’s disease (PD), the pathogenesis of PNP in PD is still a debate. The aim of this article is to search the core PD symptoms such as rigidity and tremor as contributing factors to mononeuropathy development while emphasizing each individual patient’s asymmetric symptom severity. Methods. We studied 62 wrists and 62 elbows of 31 patients (mean age ) and 64 wrists and 64 elbows of 32 age-gender matched healthy controls (mean age , ). The Hoehn and Yahr disability scale and Unified Parkinson’s Disease Rated Scale were used to determine the severity of the disease. Results. According to electrodiagnostic criteria, we confirmed median neuropathy in 16.12% (bilateral in two-thirds of the patients) and ulnar neuropathy in 3.22% of the PD group. While mean age (), age at PD onset (), and H&Y scores () were significant, tremor and rigidity scores were not. The comparison of the mean indices of electrophysiologic parameters indicated subclinical median and ulnar nerve demyelination both at the wrist and at the elbow in the patient groups where a longer disease duration and mild tremor and rigidity scores are prominent, remarkably. Conclusion. A disease related peripheral neurodegeneration beyond symptom severity occurs in PD. Nilgul Yardimci, Ozlem Cemeroglu, Eda Ozturk, Gülsüm Gürlü, Esra Şahin, Saliha Bozkurt, Tugba Cengiz, Gulderen Karali, Hasim Cakirbay, and Atilla İlhan Copyright © 2016 Nilgul Yardimci et al. All rights reserved. Classification and Characteristics of Pain Associated with Parkinson’s Disease Wed, 05 Oct 2016 09:15:22 +0000 Neuropsychiatric symptoms and pain are among the most common nonmotor symptoms of Parkinson’s disease (PD). The correlation between pain and PD has been recognized since its classic descriptions. Pain occurs in about 60% of PD patients, two to three times more frequent in this population than in age matched healthy individuals. It is an early and potentially disabling symptom that can precede motor symptoms by several years. The lower back and lower extremities are the most commonly affected areas. The most used classification for pain in PD defines musculoskeletal, dystonic, central, or neuropathic/radicular forms. Its different clinical characteristics, variable relationship with motor symptoms, and inconsistent response to dopaminergic drugs suggest that the mechanism underlying pain in PD is complex and multifaceted, involving the peripheral nervous system, generation and amplification of pain by motor symptoms, and neurodegeneration of areas related to pain modulation. Although pain in DP is common and a significant source of disability, its clinical characteristics, pathophysiology, classification, and management remain to be defined. Marcelo Rezende Young Blood, Marcelo Machado Ferro, Renato Puppi Munhoz, Hélio Afonso Ghizoni Teive, and Carlos Henrique Ferreira Camargo Copyright © 2016 Marcelo Rezende Young Blood et al. All rights reserved. Patients’ Views on a Combined Action Observation and Motor Imagery Intervention for Parkinson’s Disease Thu, 29 Sep 2016 13:44:28 +0000 Background. Action observation and motor imagery activate neural structures involved in action execution, thereby facilitating movement and learning. Although some benefits of action observation and motor imagery have been reported in Parkinson’s disease (PD), methods have been based on stroke rehabilitation and may be less suitable for PD. Moreover, previous studies have focused on either observation or imagery, yet combining these enhances effects in healthy participants. The present study explores the feasibility of a PD-specific home-based intervention combining observation, imagery, and imitation of meaningful everyday actions. Methods. A focus group was conducted with six people with mild to moderate PD and two companions, exploring topics relating to the utility and feasibility of a home-based observation and imagery intervention. Results. Five themes were identified. Participants reported their experiences of exercise and use of action observation and motor imagery in everyday activities, and the need for strategies to improve movement was expressed. Motivational factors including feedback, challenge, and social support were identified as key issues. The importance of offering a broad range of actions and flexible training was also highlighted. Conclusions. A home-based intervention utilising action observation and motor imagery would be useful and feasible in mild to moderate PD. Judith Bek, Jordan Webb, Emma Gowen, Stefan Vogt, Trevor J. Crawford, Matthew S. Sullivan, and Ellen Poliakoff Copyright © 2016 Judith Bek et al. All rights reserved. N-Acetylcysteine in Combination with IGF-1 Enhances Neuroprotection against Proteasome Dysfunction-Induced Neurotoxicity in SH-SY5Y Cells Wed, 28 Sep 2016 11:58:52 +0000 Ubiquitin proteasome system (UPS) dysfunction has been implicated in the development of many neuronal disorders, including Parkinson’s disease (PD). Previous studies focused on individual neuroprotective agents and their respective abilities to prevent neurotoxicity following a variety of toxic insults. However, the effects of the antioxidant N-acetylcysteine (NAC) on proteasome impairment-induced apoptosis have not been well characterized in human neuronal cells. The aim of this study was to determine whether cotreatment of NAC and insulin-like growth factor-1 (IGF-1) efficiently protected against proteasome inhibitor-induced cytotoxicity in SH-SY5Y cells. Our results demonstrate that the proteasome inhibitor, MG132, initiates poly(ADP-ribose) polymerase (PARP) cleavage, caspase 3 activation, and nuclear condensation and fragmentation. In addition, MG132 treatment leads to endoplasmic reticulum (ER) stress and autophagy-mediated cell death. All of these events can be attenuated without obvious reduction of MG132 induced protein ubiquitination by first treating the cells with NAC and IGF-1 separately or simultaneously prior to exposure to MG132. Moreover, our data demonstrated that the combination of the two proved to be significantly more effective for neuronal protection. Therefore, we conclude that the simultaneous use of growth/neurotrophic factors and a free radical scavenger may increase overall protection against UPS dysfunction-mediated cytotoxicity and neurodegeneration. Benxu Cheng, Pinki Anand, Anxiu Kuang, Feroz Akhtar, and Virginia L. Scofield Copyright © 2016 Benxu Cheng et al. All rights reserved. Brain MR Contribution to the Differential Diagnosis of Parkinsonian Syndromes: An Update Wed, 28 Sep 2016 11:19:15 +0000 Brain magnetic resonance (MR) represents a useful and feasible tool for the differential diagnosis of Parkinson’s disease. Conventional MR may reveal secondary forms of parkinsonism and may show peculiar brain alterations of atypical parkinsonian syndromes. Furthermore, advanced MR techniques, such as morphometric-volumetric analyses, diffusion-weighted imaging, diffusion tensor imaging, tractography, proton MR spectroscopy, and iron-content sensitive imaging, have been used to obtain quantitative parameters useful to increase the diagnostic accuracy. Currently, many MR studies have provided both qualitative and quantitative findings, reflecting the underlying neuropathological pattern of the different degenerative parkinsonian syndromes. Although the variability in the methods and results across the studies limits the conclusion about which technique is the best, specific radiologic phenotypes may be identified. Qualitative/quantitative MR changes in the substantia nigra do not discriminate between different parkinsonisms. In the absence of extranigral abnormalities, the diagnosis of PD is more probable, whereas basal ganglia changes (mainly in the putamen) suggest the diagnosis of an atypical parkinsonian syndrome. In this context, changes in pons, middle cerebellar peduncles, and cerebellum suggest the diagnosis of MSA, in midbrain and superior cerebellar peduncles the diagnosis of PSP, and in whole cerebral hemispheres (mainly in frontoparietal cortex with asymmetric distribution) the diagnosis of Corticobasal Syndrome. Giovanni Rizzo, Stefano Zanigni, Roberto De Blasi, Daniela Grasso, Davide Martino, Rodolfo Savica, and Giancarlo Logroscino Copyright © 2016 Giovanni Rizzo et al. All rights reserved. Mini Review: Anticholinergic Activity as a Behavioral Pathology of Lewy Body Disease and Proposal of the Concept of “Anticholinergic Spectrum Disorders” Thu, 22 Sep 2016 14:49:44 +0000 Given the relationship between anticholinergic activity (AA) and Alzheimer’s disease (AD), we rereview our hypothesis of the endogenous appearance of AA in AD. Briefly, because acetylcholine (ACh) regulates not only cognitive function but also the inflammatory system, when ACh downregulation reaches a critical level, inflammation increases, triggering the appearance of cytokines with AA. Moreover, based on a case report of a patient with mild AD and slightly deteriorated ACh, we also speculate that AA can appear endogenously in Lewy body disease due to the dual action of the downregulation of ACh and hyperactivity of the hypothalamic-pituitary-adrenal axis. Based on these hypotheses, we consider AA to be a behavioral pathology of Lewy body disease. We also propose the concept of “anticholinergic spectrum disorders,” which encompass a variety of conditions, including AD, Lewy body disease, and delirium. Finally, we suggest the prescription of cholinesterase inhibitors to patients in this spectrum of disorders to abolish AA by upregulating ACh. Koji Hori, Kimiko Konishi, Misa Hosoi, Hiroi Tomioka, Masayuki Tani, Yuka Kitajima, and Mitsugu Hachisu Copyright © 2016 Koji Hori et al. All rights reserved. Neuroprotective Effects of Salidroside in the MPTP Mouse Model of Parkinson’s Disease: Involvement of the PI3K/Akt/GSK3β Pathway Wed, 21 Sep 2016 10:58:06 +0000 The degenerative loss through apoptosis of dopaminergic neurons in the substantia nigra pars compacta plays a primary role in the progression of Parkinson’s disease (PD). Our in vitro experiments suggested that salidroside (Sal) could protect against 1-methyl-4-phenylpyridine-induced cell apoptosis in part by regulating the PI3K/Akt/GSK3β pathway. The current study aims to increase our understanding of the protective mechanisms of Sal in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropypridine- (MPTP-) induced PD mouse model. We found that pretreatment with Sal could protect against MPTP-induced increase of the time of turning downwards and climbing down to the floor. Sal also prevented MPTP-induced decrease of locomotion frequency and the increase of the immobile time. Sal provided a protection of in MPTP-induced loss of tyrosine hydroxylase-positive neurons in SNpc and the level of DA, DOPAC, and HVA in the striatum. Furthermore, Sal could increase the phosphorylation level of Akt and GSK3β, upregulate the ratio of Bcl-2/Bax, and inhibit the activation of caspase-3, caspase-6, and caspase-9. These results show that Sal prevents the loss of dopaminergic neurons and the PI3K/Akt/GSK3β pathway signaling pathway may have mediated the protection of Sal against MPTP, suggesting that Sal may be a potential candidate in neuroprotective treatment for PD. Wei Zhang, Hong He, Hujie Song, Junjie Zhao, Tao Li, Leitao Wu, Xiaojun Zhang, and Jianzong Chen Copyright © 2016 Wei Zhang et al. All rights reserved.