Parkinson’s Disease The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. A Randomized Controlled Trial of Chinese Medicine on Nonmotor Symptoms in Parkinson’s Disease Tue, 23 May 2017 06:55:33 +0000 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 (), mood/cognition (), and reduction in hallucinations (). In addition, post hoc analysis showed a significant reduction in constipation (). However, there was no evidence of improvement in MDS-UPDRS Part I total score () 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. Ka-Kit Chua, Adrian Wong, Kam-Wa Chan, Yin-Kei Lau, Zhao-Xiang Bian, Jia-Hong Lu, Liang-Feng Liu, Lei-Lei Chen, Ka-Ho Chan, Kim-Pong Tse, Anne Chan, Ju-Xian Song, Justin Wu, Li-Xing Zhu, Vincent Mok, and Min Li Copyright © 2017 Ka-Kit Chua et al. All rights reserved. Physiotherapy in Parkinson’s Disease: Building ParkinsonNet in Czechia Mon, 22 May 2017 08:19:14 +0000 Objective. We conducted a questionnaire survey to investigate the availability and quality of physiotherapy (PT) for Parkinson’s disease (PD). Background. Despite evidence about the benefits of PT, there is no data regarding its use in Czechia. Methods. Questionnaires were sent to 368 PD patients seen in a single movement disorders centre within two years (inclusion criteria: idiopathic PD, Hoehn and Yahr stage <5, and residence in Prague) and to 211 physical therapists (PTs) registered in Prague. The patient questionnaire evaluated limitations in 6 core areas and in activities of daily living and inquired about experience with PT. The PTs questionnaire evaluated knowledge about PD, number of PD patients treated yearly, and details of therapy. Results. Questionnaires were returned by 248 patients and 157 PTs. PT was prescribed to 70/248 patients. The effects were satisfactory in 79% and lasted >3 months in 60/64. About half of the PTs have no experience with PD patients, 26% reported <3, and 5% see >10 yearly. The most widely used techniques were neurodevelopmental treatments. Conclusion. Present PD healthcare model in Czechia is suboptimal (low PT prescription, non-evidence-based PT). Implementation of European PT Guidelines for PD and the introduction of an efficient model of care are needed. Ota Gal, Martin Srp, Romana Konvalinkova, Martina Hoskovcova, Vaclav Capek, Jan Roth, and Evzen Ruzicka Copyright © 2017 Ota Gal et al. All rights reserved. Effect of a Traditional Chinese Herbal Medicine Formulation on Cell Survival and Apoptosis of MPP+-Treated MES 23.5 Dopaminergic Cells Thu, 18 May 2017 07:40:34 +0000 Progressive degeneration of dopaminergic neurons in the substantia nigra (SN) is implicated in Parkinson’s disease (PD). The efficacy of these currently used drugs is limited while traditional Chinese medicine (TCM) has been used in the management of neurodegenerative diseases for many years. This study was designed to evaluate the effect of a modified traditional Chinese herbal medicine decoction, Cong Rong Jing (CRJ), on cell survival and apoptosis of 1-methyl-4-phenylpyridinium- (MPP+-) treated MES23.5 dopaminergic cells. CRJ was prepared as a decoction from three Chinese herbs, namely, Herba Cistanches, Herba Epimedii, and Rhizoma Polygonati. We reported here that CRJ significantly enhanced the cell survival of MES23.5 cells after the exposure of MPP+ and inhibited the production of intracellular reactive oxygen species (ROS) induced by MPP+. CRJ also prevented the MPP+-treated MES23.5 cells from apoptosis by reducing the externalization of phosphatidylserine and enhancing the Bcl-2/Bax protein expression ratio. Signaling proteins such as JAK2, STAT3, and ERK1/2 were also involved in the action of CRJ. Taken together, these results provide a preliminary mechanism to support clinical application of the TCM formulation in PD and possibly other neurodegenerative diseases associated with ROS injury and apoptosis. Shuifen Ye, Ho Kee Koon, Wen Fan, Yihui Xu, Wei Wei, Chuanshan Xu, and Jing Cai Copyright © 2017 Shuifen Ye et al. All rights reserved. Quantitative Analysis of Motor Status in Parkinson’s Disease Using Wearable Devices: From Methodological Considerations to Problems in Clinical Applications Thu, 18 May 2017 00:00:00 +0000 Long-term and objective monitoring is necessary for full assessment of the condition of patients with Parkinson’s disease (PD). Recent advances in biotechnology have seen the development of various types of wearable (body-worn) sensor systems. By using accelerometers and gyroscopes, these devices can quantify motor abnormalities, including decreased activity and gait disturbances, as well as nonmotor signs, such as sleep disturbances and autonomic dysfunctions in PD. This review discusses methodological problems inherent in wearable devices. Until now, analysis of the mean values of motion-induced signals on a particular day has been widely applied in the clinical management of PD patients. On the other hand, the reliability of these devices to detect various events, such as freezing of gait and dyskinesia, has been less than satisfactory. Quantification of disease-specific changes rather than nonspecific changes is necessary. Masahiko Suzuki, Hiroshi Mitoma, and Mitsuru Yoneyama Copyright © 2017 Masahiko Suzuki et al. All rights reserved. Genetic Variations and mRNA Expression of NRF2 in Parkinson’s Disease Tue, 02 May 2017 09:21:44 +0000 Nuclear factor erythroid 2-like 2 (NRF2) encodes a transcription factor regulating mechanisms of cellular protection and is activated by oxidative stress. NRF2 has therefore been hypothesized to confer protection against Parkinson’s disease and so far an NRF2 haplotype has been reported to decrease the risk of developing disease and delay disease onset. Also NRF2 adopts a nuclear localization in Parkinson’s disease, which is indicative of increased NRF2 activity. We have investigated the association between NRF2 and Parkinson’s disease in a Swedish case-control material and whether NRF2 expression levels correlate with NRF2 genetic variants, disease, or disease onset. Using pyrosequencing, we genotyped one intronic and three promoter variants in 504 patients and 509 control subjects from Stockholm. Further, we quantified NRF2 mRNA expression in EBV transfected human lymphocytes from patients and controls using quantitative real-time reverse transcription PCR. We found that one of the promoter variants, rs35652124, was associated with age of disease onset ( = 14.19, value = 0.0067). NRF2 mRNA expression levels however did not correlate with the rs35652124 genotype, Parkinson’s disease, or age of onset in our material. More detailed studies on NRF2 are needed in order to elucidate how this gene affects pathophysiology of Parkinson’s disease. Caroline Ran, Karin Wirdefeldt, Lovisa Brodin, Mehrafarin Ramezani, Marie Westerlund, Fengqing Xiang, Anna Anvret, Thomas Willows, Olof Sydow, Anders Johansson, Dagmar Galter, Per Svenningsson, and Andrea Carmine Belin Copyright © 2017 Caroline Ran et al. All rights reserved. Ex Vivo and In Vivo Characterization of Interpolymeric Blend/Nanoenabled Gastroretentive Levodopa Delivery Systems Wed, 26 Apr 2017 07:30:03 +0000 One approach for delivery of narrow absorption window drugs is to formulate gastroretentive drug delivery systems. This study was undertaken to provide insight into in vivo performances of two gastroretentive systems (PXLNET and IPB matrices) in comparison to Madopar® HBS capsules. The pig model was used to assess gastric residence time and pharmacokinetic parameters using blood, cerebrospinal fluid (CSF), and urine samples. Histopathology and cytotoxicity testing were also undertaken. The pharmacokinetic parameters indicated that levodopa was liberated from the drug delivery systems, absorbed, widely distributed, metabolized, and excreted. were 372.37, 257.02, and 461.28 ng/mL and MRT were 15.36, 14.98, and 13.30 for Madopar HBS capsules, PXLNET, and IPB, respectively. In addition, X-ray imaging indicated that the gastroretentive systems have the potential to reside in the stomach for 7 hours. There was strong in vitro-in vivo correlation for all formulations with values of 0.906, 0.935, and 0.945 for Madopar HBS capsules, PXLNET, and IPB, respectively. Consequently, PXLNET and IPB matrices have pertinent potential as gastroretentive systems for narrow absorption window drugs (e.g., L-dopa) and, in this application specifically, enhanced the central nervous system and/or systemic bioavailability of such drugs. Ndidi C. Ngwuluka, Yahya E. Choonara, Girish Modi, Lisa C. du Toit, Pradeep Kumar, Leith Meyer, Tracy Snyman, and Viness Pillay Copyright © 2017 Ndidi C. Ngwuluka et al. All rights reserved. Cognitive Function Characteristics of Parkinson’s Disease with Sleep Disorders Tue, 18 Apr 2017 07:21:27 +0000 Objective. The aim of this study was to investigate the cognitive function characteristics of Parkinson’s disease (PD) with sleep disorders. Methods. Consecutive patients with PD (), patients with primary sleep disorders (), and healthy control subjects () were assessed. The patients with PD were classified into sleep disorder (PD-SD) and non-sleep disorder (PD-NSD) groups. Results. Among 96 patients with PD, 69 were diagnosed with a sleep disorder. There were 38 sleep disorder cases, 31 RBD cases, and 27 NSD cases. On the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and MoCA subtests, patients in the PD-SD, primary sleep disorder, and PD-NSD groups exhibited lower scores than those in the control group. Moreover, the PD-SD patients exhibited more significant cognitive impairment than was observed in the primary sleep disorder patients. In the PD-SD subgroup, the attention scores on the MoCA and on MoCA subtests were lower in the PD with RBD group than in the PD with insomnia group. Conclusion. PD with sleep disorders may exacerbate cognitive dysfunction in patients. PD associated with different types of sleep disorders differentially affects cognitive functions, and patients with PD with RBD exhibited poorer cognitive function than was seen in patients with PD with insomnia. Jing Huang, Wenyan Zhuo, Yuhu Zhang, Hongchun Sun, Huan Chen, Peipei Zhu, Xiaobo Pan, Jianhao Yang, and Lijuan Wang Copyright © 2017 Jing Huang et al. All rights reserved. Insights into the Mechanisms Involved in Protective Effects of VEGF-B in Dopaminergic Neurons Mon, 03 Apr 2017 08:11:05 +0000 Vascular endothelial growth factor-B (VEGF-B), when initially discovered, was thought to be an angiogenic factor, due to its intimate sequence homology and receptor binding similarity to the prototype angiogenic factor, vascular endothelial growth factor-A (VEGF-A). Studies demonstrated that VEGF-B, unlike VEGF-A, did not play a significant role in angiogenesis or vascular permeability and has become an active area of interest because of its role as a survival factor in pathological processes in a multitude of systems, including the brain. By characterization of important downstream targets of VEGF-B that regulate different cellular processes in the nervous system and cardiovascular system, it may be possible to develop more effective clinical interventions in diseases such as Parkinson’s disease (PD), Amyotrophic Lateral Sclerosis (ALS), and ischemic heart disease, which all share mitochondrial dysfunction as part of the disease. Here we summarize what is currently known about the mechanism of action of VEGF-B in pathological processes. We explore its potential as a homeostatic protective factor that improves mitochondrial function in the setting of cardiovascular and neurological disease, with a specific focus on dopaminergic neurons in Parkinson’s disease. Beatrice Caballero, Scott J. Sherman, and Torsten Falk Copyright © 2017 Beatrice Caballero et al. All rights reserved. LRRK2 G2019S Mutation: Prevalence and Clinical Features in Moroccans with Parkinson’s Disease Thu, 30 Mar 2017 12:19:16 +0000 Background. The LRRK2 G2019S mutation is the most common genetic determinant of Parkinson’s disease (PD) identified to date. This mutation, reported in both familial and sporadic PD, occurs at elevated frequencies in Maghreb population. In the present study, we examined the prevalence of the G2019S mutation in the Moroccan population and we compared the motor and nonmotor phenotype of G2019S carriers to patients with idiopathic Parkinson’s disease. Methods. 100 PD patients were assessed for motor and nonmotor symptoms, current medication, and motor complication including motor fluctuations and dyskinesia. The LRRK2 G2019S mutation was investigated by direct sequencing in patients and ethnically matched controls, all of Moroccan origin. Results. Among the 100 PD Moroccan patients, 41 (41%) were carriers of the G2019S mutation. The mutation frequency was higher among probands with autosomal dominant inheritance (76%) than among sporadic ones (28%). Interestingly, G2019S mutation was also found in 5% of control individuals. Clinically, patients carrying the G2019S mutation have more dystonia (OR = 4.6, p = 0.042) and more sleep disorders (OR = 2.4, p = 0.045) than noncarriers. Conclusions. The LRRK2 G2019S prevalence in Morocco is the highest in the world reported to date. Some clinical features in G2019S carriers such as dystonia and sleep disturbances are worth noting. Ahmed Bouhouche, Houyam Tibar, Rafiqua Ben El Haj, Khalil El Bayad, Rachid Razine, Sanaa Tazrout, Asmae Skalli, Naima Bouslam, Loubna Elouardi, Ali Benomar, Mohammed Yahyaoui, and Wafa Regragui Copyright © 2017 Ahmed Bouhouche et al. All rights reserved. MRI-Guided Focused Ultrasound in Parkinson’s Disease: A Review Thu, 30 Mar 2017 00:00:00 +0000 MRI-guided focused ultrasound is a new technology that enables intracranial ablation. Since lesioning ameliorates some of the symptoms of PD, this technology is being explored as a possible treatment for medication resistant symptoms in PD patients. The purpose of this paper is to review the clinical use and treatment outcomes of PD patients treated to date with this technology. Ilana Schlesinger, Alon Sinai, and Menashe Zaaroor Copyright © 2017 Ilana Schlesinger et al. All rights reserved. Are Patients Ready for “EARLYSTIM”? Attitudes towards Deep Brain Stimulation among Female and Male Patients with Moderately Advanced Parkinson’s Disease Tue, 28 Mar 2017 07:53:42 +0000 Objective. To explore, in female and male patients with medically treated, moderately advanced Parkinson’s disease (PD), their knowledge and reasoning about Deep Brain Stimulation (DBS). Methods. 23 patients with PD (10 women), aged 46–70, were interviewed at a mean of 8 years after diagnosis, with open-ended questions concerning their reflections and considerations about DBS. The interviews were transcribed verbatim and analysed according to the difference and similarity technique in Grounded Theory. Results. From the patients’ narratives, the core category “Processing DBS: balancing symptoms, fears and hopes” was established. The patients were knowledgeable about DBS and expressed cautious and well considered attitudes towards its outcome but did not consider themselves ill enough to undergo DBS. They were aware of its potential side-effects. They considered DBS as the last option when oral medication is no longer sufficient. There was no difference between men and women in their reasoning and attitudes towards DBS. Conclusion. This study suggests that knowledge about the pros and cons of DBS exists among PD patients and that they have a cautious attitude towards DBS. Our patients did not seem to endorse an earlier implementation of DBS, and they considered that it should be the last resort when really needed. Maria Sperens, Katarina Hamberg, and Gun-Marie Hariz Copyright © 2017 Maria Sperens et al. All rights reserved. Correlation of MRI Visual Scales with Neuropsychological Profile in Mild Cognitive Impairment of Parkinson’s Disease Sun, 19 Mar 2017 10:20:14 +0000 Few studies have evaluated magnetic resonance imaging (MRI) visual scales in Parkinson’s disease-Mild Cognitive Impairment (PD-MCI). We selected 79 PD patients and 92 controls (CO) to perform neurologic and neuropsychological evaluation. Brain MRI was performed to evaluate the following scales: Global Cortical Atrophy (GCA), Fazekas, and medial temporal atrophy (MTA). The analysis revealed that both PD groups (amnestic and nonamnestic) showed worse performance on several tests when compared to CO. Memory, executive function, and attention impairment were more severe in amnestic PD-MCI group. Overall analysis of frequency of MRI visual scales by MCI subtype did not reveal any statistically significant result. Statistically significant inverse correlation was observed between GCA scale and Mini-Mental Status Examination (MMSE), Montreal Cognitive Assessment (MoCA), semantic verbal fluency, Stroop test, figure memory test, trail making test (TMT) B, and Rey Auditory Verbal Learning Test (RAVLT). The MTA scale correlated with Stroop test and Fazekas scale with figure memory test, digit span, and Stroop test according to the subgroup evaluated. Visual scales by MRI in MCI should be evaluated by cognitive domain and might be more useful in more severely impaired MCI or dementia patients. Luiz Felipe Vasconcellos, João Santos Pereira, Marcelo Adachi, Denise Greca, Manuela Cruz, Ana Lara Malak, Helenice Charchat-Fichman, and Mariana Spitz Copyright © 2017 Luiz Felipe Vasconcellos et al. All rights reserved. Rivastigmine as a Symptomatic Treatment for Apathy in Parkinson’s Dementia Complex: New Aspects for This Riddle Sun, 19 Mar 2017 07:06:05 +0000 Over 90% of PDD patients show at least one neuropsychiatric symptom (NPS); in the 60–70% two or more NPS are present. Their incidence is important in terms of prognosis and severity of pathology. However, among all NPS, apathy is often the most disturbing, associated with greater caregiver’s burden. Similar to other NPS, apathy may be due to a dysfunction of the nigrostriatal pathway, even though, not all the PD patients become apathetic, indicating that apathy should not entirely be considered a dopamine-dependent syndrome, and in fact it might also be related to acetylcholine defects. Apathy has been treated in many ways, without sure benefits; among these, Rivastigmine may present benefic properties. We present a series of 48 patients, suffering from PDD, treated with Rivastigmine, and followed-up for one year; they have been devotedly studied for apathy, even though all the other NPS disorders have been registered. Rivastigmine did not have a prolonged benefic effect on apathy, in our work, on the contrary of what had been observed in the literature, probably due to the longer follow-up of our patients. Rita Moretti, Paola Caruso, and Matteo Dal Ben Copyright © 2017 Rita Moretti et al. All rights reserved. Protective Effects of an Ancient Chinese Kidney-Tonifying Formula against H2O2-Induced Oxidative Damage to MES23.5 Cells Sun, 12 Mar 2017 00:00:00 +0000 Oxidative damage plays a critical role in the etiology of neurodegenerative disorders including Parkinson’s disease (PD). In our study, an ancient Chinese kidney-tonifying formula, which consists of Cistanche, Epimedii, and Polygonatum cirrhifolium, was investigated to protect MES23.5 dopaminergic neurons against hydrogen peroxide- (H2O2-) induced oxidative damage. The damage effects of H2O2 on MES23.5 cells and the protective effects of KTF against oxidative stress were evaluated using MTT assay, transmission electron microscopy (TEM), immunocytochemistry (ICC), enzyme-linked immunosorbent assay (ELISA), and immunoblotting. The results showed that cell viability was dramatically decreased after a 12 h exposure to 150 μM H2O2. TEM observation found that the H2O2-treated MES23.5 cells presented cellular organelle damage. However, when cells were incubated with KTF (3.125, 6.25, and 12.5 μg/ml) for 24 h after H2O2 exposure, a significant protective effect against H2O2-induced damage was observed in MES23.5 cells. Using ICC, we found that KTF inhibited the reduction of the tyrosine hydroxylase (TH) induced by H2O2, upregulated the mRNA and protein expression of HO-1, CAT, and GPx-1, and downregulated the expression of caspase 3. These results indicated that KTF may provide neuron protection against H2O2-induced cell damage through ameliorating oxidative stress, and our findings provide a new potential strategy for the prevention and treatment of Parkinson’s disease. Yihui Xu, Wei Lin, Shuifen Ye, Huajin Wang, Tingting Wang, Youyan Su, Liangning Wu, Yuanwang Wang, Qian Xu, Chuanshan Xu, and Jing Cai Copyright © 2017 Yihui Xu et al. All rights reserved. Festination Correlates with SNCA Polymorphism in Chinese Patients with Parkinson’s Disease Sun, 05 Mar 2017 00:00:00 +0000 The genetic basis of festination, a common motor symptom in Parkinson’s disease (PD), remains unclear. Since polymorphism in the alpha-synuclein (SNCA) gene is associated with PD phenotype, we examined whether such polymorphism is also associated with festination. SNCA polymorphisms rs11931074 and rs894278 were genotyped in a consecutive series of 258 patients with PD, of whom 122 (47.3%) suffered festination. Univariate analysis revealed significant differences in genotype and minor allele frequencies at rs11931074 or rs894278 between patients with festination and those without it (all ). Based on logistic regression, a GG or GT genotype at rs11931074 was associated with higher risk of festination among patients with PD (OR 2.077, 95% CI 1.111–3.883, ), as was the TT genotype at rs894278 (OR 2.271, 95% CI 1.246–4.139, ). Therefore, we conclude that festination is associated with polymorphism at rs11931074 or rs894278 among patients with PD. Jinhua Zheng, Xinglong Yang, Quanzhen Zhao, Sijia Tian, Hongyan Huang, Yalan Chen, and Yanming Xu Copyright © 2017 Jinhua Zheng et al. All rights reserved. Systematic Review and Critical Analysis of Cost Studies Associated with Parkinson’s Disease Sun, 05 Mar 2017 00:00:00 +0000 Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease worldwide, affecting more than four million people. Typically, it affects individuals above 45, when they are still productive, compromising both aging and quality of life. Therefore, the cost of the disease must be identified, so that the use of resources can be rational and efficient. Additionally, in Brazil, there is a lack of research on the costs of neurodegenerative diseases, such as PD, a gap addressed in this study. This systematic review critically addresses the various methodologies used in original research around the world in the last decade on the subject, showing that costs are hardly comparable. Nonetheless, the economic and social impacts are implicit, and important information for public health agents is provided. Tânia M. Bovolenta, Sônia Maria Cesar de Azevedo Silva, Roberta Arb Saba, Vanderci Borges, Henrique Ballalai Ferraz, and Andre C. Felicio Copyright © 2017 Tânia M. Bovolenta et al. All rights reserved. Nonmotor Symptoms of Parkinson’s Disease Thu, 02 Mar 2017 07:12:50 +0000 Shey-Lin Wu, Rajka M. Liscic, SangYun Kim, Sandro Sorbi, and Yuan-Han Yang Copyright © 2017 Shey-Lin Wu et al. All rights reserved. Cost of Living with Parkinson’s Disease over 12 Months in Australia: A Prospective Cohort Study Thu, 02 Mar 2017 00:00:00 +0000 Background. Parkinson disease (PD) is a costly chronic condition in terms of managing both motor and nonmotor symptoms. The burden of disease is high for individuals, caregivers, and the health system. The aim of this study is to estimate the annual cost of PD from the household, health system, and societal perspectives. Methods. A prospective cohort study of newly referred people with PD to a specialist PD clinic in Melbourne, Australia. Participants completed baseline and monthly health resource use questionnaires and Medicare data were collected over 12 months. Results. 87 patients completed the 12-month follow-up assessments. The mean annual cost per person to the health care system was $32,556 AUD. The burden to society was an additional $45,000 per annum per person with PD. The largest component of health system costs were for hospitalisation (69% of total costs). The costs for people with moderate to severe disease were almost 4 times those with mild PD ($63,569 versus $17,537 ). Conclusion. PD is associated with significant costs to individuals and to society. Costs escalated with disease severity suggesting that the burden to society is likely to grow with the increasing disease prevalence that is associated with population ageing. Shalika Bohingamu Mudiyanselage, Jennifer J. Watts, Julie Abimanyi-Ochom, Lisa Lane, Anna T. Murphy, Meg E. Morris, and Robert Iansek Copyright © 2017 Shalika Bohingamu Mudiyanselage et al. All rights reserved. The Level of Knowledge of Parkinson’s Disease among Nonprofessional Caregivers in a Movement Disorders Center in Turkey Wed, 01 Mar 2017 10:38:14 +0000 Introduction. Only a few studies have been conducted to determine the level of knowledge among caregivers about Parkinson’s disease (PD). The aim of the current study was to determine the knowledge of PD among caregivers at a movement disorder clinic in Turkey. Methods. We conducted a questionnaire based interview with the subjects in a tertiary care neurology facility in Turkey. The questions were divided into two parts covering the symptomatology and treatment of PD. A questionnaire consisting of 10 questions was applied to the subjects who had to mark the correct option in a stipulated time. Results. Eighty caregivers were included in the study. The caregivers’ mean age was 47.94 years (SD = 12.40). There were 47 female caregivers (58.8%). The most well-known question was that the number of drugs given to the patient may vary with time (76.3%), whereas “the benefit noted in the patient’s treatment decreases over time” was the least known question (11.3%). Discussion. This study is the first in our country and shows the necessity to increase the knowledge of PD among caregivers and the public. Education programs may have a positive role in imparting knowledge to the caregivers of PD patients. Murat Gultekin, Ayse Caglar Sarılar, Ayten Ekinci, Gozde Erturk, and Meral Mirza Copyright © 2017 Murat Gultekin et al. All rights reserved. Correlation of Visuospatial Ability and EEG Slowing in Patients with Parkinson’s Disease Tue, 28 Feb 2017 11:16:13 +0000 Background. Visuospatial dysfunction is among the first cognitive symptoms in Parkinson’s disease (PD) and is often predictive for PD-dementia. Furthermore, cognitive status in PD-patients correlates with quantitative EEG. This cross-sectional study aimed to investigate the correlation between EEG slowing and visuospatial ability in nondemented PD-patients. Methods. Fifty-seven nondemented PD-patients (17 females/40 males) were evaluated with a comprehensive neuropsychological test battery and a high-resolution 256-channel EEG was recorded. A median split was performed for each cognitive test dividing the patients sample into either a normal or lower performance group. The electrodes were split into five areas: frontal, central, temporal, parietal, and occipital. A linear mixed effects model (LME) was used for correlational analyses and to control for confounding factors. Results. Subsequently, for the lower performance, LME analysis showed a significant positive correlation between ROCF score and parietal alpha/theta ratio (, ) and occipital alpha/theta ratio (, ). No correlations were found in the group of patients with normal visuospatial abilities. Conclusion. We conclude that a reduction of the parietal alpha/theta ratio is related to visuospatial impairments in PD-patients. These findings indicate that visuospatial impairment in PD-patients could be influenced by parietal dysfunction. Dominique Eichelberger, Pasquale Calabrese, Antonia Meyer, Menorca Chaturvedi, Florian Hatz, Peter Fuhr, and Ute Gschwandtner Copyright © 2017 Dominique Eichelberger et al. 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.