Parkinson’s Disease The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Deep Brain Stimulation Can Preserve Working Status in Parkinson’s Disease Thu, 30 Jul 2015 11:29:27 +0000 Objectives. Our investigation aimed at evaluating if bilateral subthalamic deep brain stimulation (DBS) could preserve working capability in Parkinson’s disease (PD). Materials. We reviewed the data of 40 young (<60 year-old) PD patients who underwent DBS implantation and had at least 2 years of follow-up. Patients were categorized based on their working capability at time of surgery: “active job” group () and “no job” group (). Baseline characteristics were comparable. Quality of life (EQ-5D) and presence of active job were evaluated preoperatively and 2 years postoperatively. Results. Although similar (approximately 50%) improvement was achieved in the severity of motor and major nonmotor symptoms in both groups, the postoperative quality of life was significantly better in the “active job” group (0.687 versus 0.587, medians, ). Majority (80%) of “active job” group members were able to preserve their job 2 years after the operation. However, only a minimal portion (5%) of the “no job” group members was able to return to the world of active employees (). Conclusions. Although our study has several limitations, our results suggest that in patients with active job the appropriately “early” usage of DBS might help preserve working capability and gain higher improvement in quality of life. Gabriella Deli, István Balás, Tamás Dóczi, József Janszky, Kázmér Karádi, Zsuzsanna Aschermann, Ferenc Nagy, Attila Makkos, Márton Kovács, Edit Bosnyák, Norbert Kovács, and Sámuel Komoly Copyright © 2015 Gabriella Deli et al. All rights reserved. The Diagnostic and Differential Diagnosis Utility of Cerebrospinal Fluid α-Synuclein Levels in Parkinson’s Disease: A Meta-Analysis Wed, 29 Jul 2015 07:32:31 +0000 Several recent studies showed that α-syn might be a potential diagnostic biomarker for PD in human cerebrospinal fluid (CSF), but the results were inconsistent. The purpose of this meta-analysis was to investigate the diagnostic and differential diagnosis efficacy of CSF α-syn in PD. Studies which measured CSF α-syn or α-syn oligomers in patients with PD and met the inclusion criteria were included in the analysis. Results of the meta-analysis indicated that mean concentration of CSF α-syn was significantly lower in PD compared to controls and significantly higher in PD compared to multiple system atrophy (MSA). No significant difference in mean concentration of CSF α-syn was found between PD and dementia with Lewy bodies (DLB). Mean concentration of CSF α-syn was slightly decreased in PD compared to progressive supranuclear palsy (PSP). Mean concentration of CSF α-syn oligomers was significantly higher in PD than control. These results support the findings that CSF α-syn may be a potential diagnostic and differential diagnosis biomarker in PD compared to control and MSA but not DLB. Furthermore, α-syn oligomer may represent a better biomarker for diagnosis of PD. Bo Zhou, Min Wen, Wen-Feng Yu, Chun-Lin Zhang, and Ling Jiao Copyright © 2015 Bo Zhou et al. All rights reserved. Polymorphism in the Vesicular Monoamine Transporter 2 Gene Decreases the Risk of Parkinson’s Disease in Han Chinese Men Sun, 12 Jul 2015 07:11:00 +0000 Background. Polymorphisms rs363371 and rs363324 in the vesicular monoamine transporter 2 (VMAT2) gene have been associated with risk of PD in an Italian population, and our aim is to investigate the association between the two single-nucleotide polymorphisms and PD in Han Chinese. Methods. 561 Han Chinese PD patients and 491 healthy age- and gender-matched controls were genotyped using Ligase detection reaction (LDR) method. Result. Both of patient and control groups showed similar genotype frequencies between patients and controls at both rs363371 and rs363324, as well as similar minor A allele frequencies at rs363371 () and rs363324 (). None of the observed haplotypes showed a significant association with PD. Subgroup analysis by gender and age at onset revealed a significant association between the A allele of rs363371 and PD in Han Chinese males relative to healthy controls (OR 0.799, 95%  CI 0.665 to 0.959, ), and this association remained significant after adjusting for age (OR 0.785, 95%  CI 0.652 to 0.945, ). Conclusion. These results suggest that polymorphism of VMAT2 locus is associated with risk of PD in Han Chinese overall but that the A allele at rs363371 may protect against PD in Han Chinese males. Xinglong Yang, Pingrong Xu, Quanzhen Zhao, Ran An, Hua Jia, Zhuolin Liu, and Yanming Xu Copyright © 2015 Xinglong Yang et al. All rights reserved. Validation of the Official Slovak Version of the Unified Dyskinesia Rating Scale (UDysRS) Thu, 02 Jul 2015 07:17:48 +0000 After successful clinimetric testing of the Unified Dyskinesia Rating Scale (UDysRS), a program for translation and validation of non-English versions of the UDysRS was initiated. The aim of this study was to validate and confirm the factor structure of the Slovak translation of the UDysRS. We examined 251 patients with Parkinson’s disease and dyskinesia using the Slovak version of the UDysRS. The average age of our sample was 65.2 ± 9.2 years and average disease duration was 10.9 ± 5.0 years. Slovak data were compared using confirmatory factor analysis with the Spanish data. To be designated as the official Slovak UDysRS translation, the comparative fit index (CFI) had to be 0.90 relative to the Spanish language version. Exploratory factor analysis was performed to explore the underlying factor structure without the constraint of a prespecified factor structure. For all four parts of the Slovak UDysRS, the CFI, in comparison with the Spanish language factor structure, was 0.98. Isolated differences in the factor structure of the Slovak UDysRS were identified by exploratory factor analysis compared with the Spanish version. The Slovak version of the UDysRS was designated as an official non-English translation and can be downloaded from the website of the International Parkinson and Movement Disorder Society. Matej Skorvanek, Michal Minar, Milan Grofik, Katarina Kracunova, Vladimir Han, Frantisek Cibulcik, Jan Necpal, Ladislav Gurcik, and Peter Valkovic Copyright © 2015 Matej Skorvanek et al. All rights reserved. Corrigendum to “Changes in Vowel Articulation with Subthalamic Nucleus Deep Brain Stimulation in Dysarthric Speakers with Parkinson’s Disease” Thu, 02 Jul 2015 06:12:22 +0000 Vincent Martel Sauvageau, Joël Macoir, Mélanie Langlois, Michel Prud’Homme, Léo Cantin, and Johanna-Pascale Roy Copyright © 2015 Vincent Martel Sauvageau et al. All rights reserved. Self-Reported Executive Functioning in Everyday Life in Parkinson’s Disease after Three Months of Subthalamic Deep Brain Stimulation Thu, 18 Jun 2015 07:09:33 +0000 Objective. Studies on the effect of subthalamic deep brain stimulation (STN-DBS) on executive functioning in Parkinson’s disease (PD) are still controversial. In this study we compared self-reported daily executive functioning in PD patients before and after three months of STN-DBS. We also examined whether executive functioning in everyday life was associated with motor symptoms, apathy, and psychiatric symptoms. Method. 40 PD patients were examined with the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A), the Symptom Checklist 90-Revised (SCL-90-R), and the Apathy Evaluation Scale (AES-S). Results. PD patients reported significant improvement in daily life executive functioning after 3 months of STN-DBS. Anxiety scores significantly declined, while other psychiatric symptoms remained unchanged. The improvement of self-reported executive functioning did not correlate with motor improvement after STN-DBS. Apathy scores remained unchanged after surgery. Only preoperative depressed mood had predictive value to the improvement of executive function and appears to prevent potentially favorable outcomes from STN-DBS on some aspects of executive function. Conclusion. PD patients being screened for STN-DBS surgery should be evaluated with regard to self-reported executive functioning. Depressive symptoms in presurgical PD patients should be treated. Complementary information about daily life executive functioning in PD patients might enhance further treatment planning of STN-DBS. Uyen Ha Gia Pham, Stein Andersson, Mathias Toft, Are Hugo Pripp, Ane Eidahl Konglund, Espen Dietrichs, Ulrik Fredrik Malt, Inger Marie Skogseid, Ira Ronit Hebolt Haraldsen, and Anne-Kristin Solbakk Copyright © 2015 Uyen Ha Gia Pham et al. All rights reserved. The Effect of Visual Feedback on Writing Size in Parkinson’s Disease Wed, 17 Jun 2015 11:57:12 +0000 Parkinson’s disease (PD) leads to impairment in multiple cognitive domains. Micrographia is a relatively early PD sign of visuomotor dysfunction, characterized by a global reduction in writing size and a decrement in size during writing. Here we aimed to investigate the effect of withdrawal of visual feedback on writing size in patients with PD. Twenty-five patients with non-tremor-dominant PD without cognitive dysfunction and twenty-five age-matched controls had to write a standard sentence with and without visual feedback. We assessed the effect of withdrawal of visual feedback by measuring vertical word size (i), horizontal length of the sentence (ii), and the summed horizontal word length without interspacing (iii), comparing patients with controls. In both patients and controls, writing was significantly larger without visual feedback. This enlargement did not significantly differ between the groups. Smaller handwriting significantly correlated with increased disease severity. Contrary to previous observations that withdrawal of visual feedback caused increased writing size in specifically PD, we did not find differences between patients and controls. Both groups wrote larger without visual feedback, which adds insight in general neuronal mechanisms underlying the balance between feed-forward and feedback in visuomotor control, mechanisms that also hold for grasping movements. Adriaan R. E. Potgieser, Elizabeth Roosma, Martijn Beudel, and Bauke M. de Jong Copyright © 2015 Adriaan R. E. Potgieser et al. All rights reserved. Abnormal Cerebrovascular Reactivity in Patients with Parkinson’s Disease Tue, 16 Jun 2015 06:18:28 +0000 Background. Orthostatic hypotension (OH) is an important nonmotor manifestation of Parkinson’s disease (PD). Changes in cerebrovascular reactivity may contribute to this manifestation and can be monitored using transcranial Doppler. Objective. To identify possible changes in cerebrovascular reactivity in patients with OH. Methods. Twenty-two individuals were selected and divided into three groups: with and without OH and controls. Transcranial Doppler was used to assess basal mean blood flow velocity, postapnea mean blood flow velocity, percentage increase in mean blood flow velocity, and cerebrovascular reactivity as measured by the breath-holding index. Results. PD patients had lower values of basal velocity (), postapnea velocity (), percentage increase in velocity (), and breath-holding index () than the controls. Patients with OH had higher values of basal velocity () and postapnea velocity () but lower values of percentage increase in velocity () and breath-holding index () than patients without OH. Conclusions. PD patients present with abnormalities in a compensatory mechanism that regulates cerebral blood flow. OH could be an indicator of these abnormalities. Carlos Henrique Ferreira Camargo, Eduardo Antunes Martins, Marcos Christiano Lange, Henrique Alvaro Hoffmann, Jissa Jeanete Luciano, Marcelo Rezende Young Blood, Marcelo Derbli Schafranski, Marcelo Machado Ferro, and Edmar Miyoshi Copyright © 2015 Carlos Henrique Ferreira Camargo et al. All rights reserved. Orbitofrontal 18F-DOPA Uptake and Movement Preparation in Parkinson’s Disease Thu, 11 Jun 2015 12:22:23 +0000 In Parkinson’s disease (PD) degeneration of mesocortical dopaminergic projections may determine cognitive and behavioral symptoms. Choice reaction time task is related to attention, working memory, and goal-directed behavior. Such paradigm involves frontal cortical circuits receiving mesocortical dopamine which are affected early in PD. The aim of this study is to characterize the role of dopamine on the cognitive processes that precede movement in a reaction time paradigm in PD. We enrolled 16 newly diagnosed and untreated patients with PD without cognitive impairment or depression and 10 control subjects with essential tremor. They performed multiple-choice reaction time task with the right upper limb and brain 18F-DOPA PET/CT scan. A significant inverse correlation was highlighted between average reaction time and 18F-DOPA uptake in the left lateral orbitofrontal cortex. No correlations were found between reaction time and PD disease severity or between reaction time and 18F-DOPA uptake in controls. Our study shows that in PD, but not in controls, reaction time is inversely related to the levels of dopamine in the left lateral orbitofrontal cortex. This novel finding underlines the role of dopamine in the lateral orbitofrontal cortex in the early stages of PD, supporting a relation between the compensatory cortical dopamine and movement preparation. Lucio Marinelli, Arnoldo Piccardo, Laura Mori, Silvia Morbelli, Nicola Girtler, Antonio Castaldi, Agnese Picco, Carlo Trompetto, Maria Felice Ghilardi, Giovanni Abbruzzese, and Flavio Nobili Copyright © 2015 Lucio Marinelli et al. All rights reserved. L-Dopa Pharmacokinetic Profile with Effervescent Melevodopa/Carbidopa versus Standard-Release Levodopa/Carbidopa Tablets in Parkinson’s Disease: A Randomised Study Wed, 10 Jun 2015 12:44:29 +0000 Objectives. To characterize the pharmacokinetic profile of levodopa (L-dopa) and carbidopa after repeated doses of the effervescent tablet of melevodopa/carbidopa (V1512; Sirio) compared with standard-release L-dopa/carbidopa in patients with fluctuating Parkinson’s disease. Few studies assessed the pharmacokinetics of carbidopa to date. Methods. This was a single-centre, randomized, double-blind, double-dummy, two-period crossover study. Patients received V1512 (melevodopa 100 mg/carbidopa 25 mg) or L-dopa 100 mg/carbidopa 25 mg, 7 doses over 24 hours (Cohort 1), 4 doses over 12 hours (Cohort 2), or 2 doses over 12 hours in combination with entacapone 200 mg (Cohort 3). Pharmacokinetic parameters included area under the plasma-concentration time curve (AUC), maximum plasma concentration (), and time to (). Results. Twenty-five patients received at least one dose of study medication. L-dopa absorption tended to be quicker and pharmacokinetic parameters less variable after V1512 versus L-dopa/carbidopa, both over time and between patients. Accumulation of L-dopa in plasma was less noticeable with V1512. Carbidopa exposure and interpatient variability was lower when V1512 or L-dopa/carbidopa was given in combination with entacapone. Both treatments were well tolerated. Conclusions. V1512 provides a more reliable L-dopa pharmacokinetic profile versus standard-release L-dopa/carbidopa, with less drug accumulation and less variability. This trial is registered with NCT00491998. Fabrizio Stocchi, Laura Vacca, Paola Grassini, Stephen Pawsey, Holly Whale, Stefano Marconi, and Margherita Torti Copyright © 2015 Fabrizio Stocchi et al. All rights reserved. Clinical Features Associated with Frozen Shoulder Syndrome in Parkinson’s Disease Tue, 09 Jun 2015 07:26:48 +0000 Background. Frozen shoulder syndrome is a common musculoskeletal disease of idiopathic Parkinson’s disease (PD) that causes long-term pain and physical disability. A better understanding of the associated factors can help identify PD patients who will require prevention to improve their quality of life. Methodology. This prospective study evaluated 60 shoulders of 30 PD patients. Correlation analysis was used to evaluate the relationships between clinical factors and shoulder sonography findings. Results. Frozen shoulder syndrome was found in 14 of 30 PD patients affecting 19 shoulders, including bilateral involvement in five and unilateral involvement in nine. There was a significant positive correlation between the parameters of sonography findings and frozen shoulder syndrome (i.e., thickness of bicipital effusion and tendon thickness of the subscapularis and supraspinatus) and mean ipsilateral Unified Parkinson’s Disease Rating Scale (UPDRS) III and its subscores (tremor, rigidity, and bradykinesia scores). Conclusions. Higher ipsilateral UPDRS and subscores are associated with increased effusion around the biceps tendon, with increased tendon thickness of subscapularis and supraspinatus. Preventing frozen shoulder syndrome in the high-risk PD group is an important safety issue and highly relevant for their quality of life. Ya-Ting Chang, Wen-Neng Chang, Nai-Wen Tsai, Kuei-Yueh Cheng, Chih-Cheng Huang, Chia-Te Kung, Yu-Jih Su, Wei-Che Lin, Ben-Chung Cheng, Chih-Min Su, Yi-Fang Chiang, and Cheng-Hsien Lu Copyright © 2015 Ya-Ting Chang et al. All rights reserved. Mindfulness Training among Individuals with Parkinson’s Disease: Neurobehavioral Effects Tue, 26 May 2015 09:24:43 +0000 Objective. To investigate possible neurobehavioral changes secondary to a mindfulness based intervention (MBI) training for individuals living with Parkinson’s disease (PD). Background. In the context of complementary medicine, MBIs are increasingly being used for stress reduction and in patient populations coping with chronic illness. The use of alternative and complementary medicine may be higher in patients with chronic conditions such as PD. However, behavioral effects of mindfulness training in PD have not yet been reported in the literature and this points to an unmet need and warrants further examination. Methods. A total of 27 out of 30 PD patients completed a randomized controlled longitudinal trial. Questionnaires and the UPDRS I–IV were obtained at baseline and 8-week follow-up. Results. Significant changes after the MBI were found including a 5.5 point decrease on the UPDRS motor score, an increase of 0.79 points on Parkinson’s disease questionnaire (PDQ-39) pain item, and a 3.15 point increase in the Five Facet Mindfulness Questionnaire observe facet. Conclusions. To the best of our knowledge, this is the first quantitative analysis of neurobehavioral effects of MBI in PD. Barbara Pickut, Sven Vanneste, Mark A. Hirsch, Wim Van Hecke, Eric Kerckhofs, Peter Mariën, Paul M. Parizel, David Crosiers, and Patrick Cras Copyright © 2015 Barbara Pickut et al. All rights reserved. Parkinson’s Disease and Home Healthcare Use and Expenditures among Elderly Medicare Beneficiaries Sun, 24 May 2015 11:41:11 +0000 This study estimated excess home healthcare use and expenditures among elderly Medicare beneficiaries (age ≥ 65 years) with Parkinson’s disease (PD) compared to those without PD and analyzed the extent to which predisposing, enabling, need factors, personal health choice, and external environment contribute to the excess home healthcare use and expenditures among individuals with PD. A retrospective, observational, cohort study design using Medicare 5% sample claims for years 2006-2007 was used for this study. Logistic regressions and Ordinary Least Squares regressions were used to assess the association of PD with home health use and expenditures, respectively. Postregression nonlinear and linear decomposition techniques were used to understand the extent to which differences in home healthcare use and expenditures among elderly Medicare beneficiaries with and without PD can be explained by individual-level factors. Elderly Medicare beneficiaries with PD had higher home health use and expenditures compared to those without PD. 27.5% and 18% of the gap in home health use and expenditures, respectively, were explained by differences in characteristics between the PD and no PD groups. A large portion of the differences in home healthcare use and expenditures remained unexplained. Sandipan Bhattacharjee, Aaron Metzger, Cindy Tworek, Wenhui Wei, Xiaoyun Pan, and Usha Sambamoorthi Copyright © 2015 Sandipan Bhattacharjee et al. All rights reserved. Effects of Age and Gender on Hand Motion Tasks Sun, 24 May 2015 07:12:57 +0000 Objective. Wearable and wireless motion sensor devices have facilitated the automated computation of speed, amplitude, and rhythm of hand motion tasks. The aim of this study is to determine if there are any biological influences on these kinematic parameters. Methods. 80 healthy subjects performed hand motion tasks twice for each hand, with movements measured using a wireless motion sensor device (Kinesia, Cleveland Medical Devices Inc., Cleveland, OH). Multivariate analyses were performed with age, gender, and height added into the model. Results. Older subjects performed poorer in finger tapping (FT) speed (, ), hand-grasp (HG) speed (, ), and pronation-supination (PS) speed (, ). Men performed better in FT rhythm , HG speed , HG amplitude , and HG rhythm . Taller subjects performed better in the speed and amplitude components of FT and HG tasks . After multivariate analyses, only age and gender emerged as significant independent factors influencing the speed but not the amplitude and rhythm components of hand motion tasks. Gender exerted an independent influence only on HG speed, with better performance in men . Conclusions. Age, gender, and height are not independent factors influencing the amplitude and rhythm components of hand motion tasks. The speed component is affected by age and gender differences. Wing Lok Au, Irene Soo Hoon Seah, Wei Li, and Louis Chew Seng Tan Copyright © 2015 Wing Lok Au et al. All rights reserved. Person-Centered Care in the Home Setting for Parkinson’s Disease: Operation House Call Quality of Care Pilot Study Tue, 19 May 2015 10:30:59 +0000 Objective. (1) To evaluate the feasibility of implementing and evaluating a home visit program for persons with Parkinson’s disease (PD) in a rural setting. (2) To have movement disorders fellows coordinate and manage health care delivery. Background. The University of Florida, Center for Movement Disorders and Neurorestoration established Operation House Call to serve patients with PD who could not otherwise afford to travel to an expert center or to pay for medical care. PD is known to lead to significant disability, frequent hospitalization, early nursing home placement, and morbidity. Methods. This was designed as a quality improvement project. Movement disorders fellows travelled to the home(s) of underserved PD patients and coordinated their clinical care. The diagnosis of Parkinson’s disease was confirmed using standardized criteria, and the Unified Parkinson’s Disease Rating Scale was performed and best treatment practices were delivered. Results. All seven patients have been followed up longitudinally every 3 to 6 months in the home setting, and they remain functional and independent. None of the patients have been hospitalized for PD related complications. Each patient has a new updatable electronic medical record. All Operation House Call cases are presented during video rounds for the interdisciplinary PD team to make recommendations for care (neurology, neurosurgery, neuropsychology, psychiatry, physical therapy, occupational therapy, speech therapy, and social work). One Operation House Call patient has successfully received deep brain stimulation (DBS). Conclusion. This program is a pilot program that has demonstrated that it is possible to provide person-centered care in the home setting for PD patients. This program could provide a proof of concept for the construction of a larger visiting physician or nurse program. Nawaz Hack, Umer Akbar, Erin H. Monari, Amanda Eilers, Amanda Thompson-Avila, Nelson H. Hwynn, Ashok Sriram, Ihtsham Haq, Angela Hardwick, Irene A. Malaty, and Michael S. Okun Copyright © 2015 Nawaz Hack et al. All rights reserved. Pharmacokinetic Study and Optimal Formulation of New Anti-Parkinson Natural Compound Schisantherin A Sun, 17 May 2015 08:57:49 +0000 Our recent studies showed that schisantherin A (StA) is a promising candidate for PD treatment, but the pharmacokinetic profile of StA is largely unknown. The effects of different formulations on the pharmacokinetics and bioavailability of StA were investigated by HPLC equipped with a vacuum degasser, a quaternary pump, a manual sampler, and an ultraviolet detector. The absolute bioavailability of StA in nanoemulsion formulation was significantly increased from 4.3% to 47.3%. To the best of our knowledge, this is the first report of absolute bioavailability for StA in rats and successful increase of bioavailability of StA by nanoemulsion formulation. The pharmacokinetic profiles of StA could be significantly improved by a safe nanoemulsion formulation. This study provides a successful example of advanced delivery system for improving the bioavailability of potential central nervous system (CNS) drug candidate with poor solubility. This novel approach could be an effective alternative solution to overcome the shortcomings of conventional poor drug delivery of CNS drugs. The results of present study not only indicate that StA has potential to be developed as a promising oral therapeutic agent for the management of PD but also shed light on novel way to improve bioavailability of PD drugs. Fei Sa, Bao Jian Guo, Sai Li, Zai Jun Zhang, Hok Man Chan, Ying Zheng, and Simon Ming Yuen Lee Copyright © 2015 Fei Sa et al. All rights reserved. Visual Hallucinations as Incidental Negative Effects of Virtual Reality on Parkinson’s Disease Patients: A Link with Neurodegeneration? Sun, 10 May 2015 09:53:21 +0000 We followed up a series of 23 Parkinson’s disease (PD) patients who had performed an immersive virtual reality (VR) protocol eight years before. On that occasion, six patients incidentally described visual hallucinations (VH) with occurrences of images not included in the virtual environment. Curiously, in the following years, only these patients reported the appearance of VH later in their clinical history, while the rest of the group did not. Even considering the limited sample size, we may argue that VR immersive systems can induce unpleasant effects in PD patients who are predisposed to a cognitive impairment. Giovanni Albani, Elisa Pedroli, Pietro Cipresso, Daniel Bulla, Veronica Cimolin, Astrid Thomas, Alessandro Mauro, and Giuseppe Riva Copyright © 2015 Giovanni Albani et al. All rights reserved. Association Analysis of COQ2 Variant in Dementia and Essential Tremor Wed, 22 Apr 2015 11:16:28 +0000 Objective. COQ2 mutations have been reported in Japanese multiple system atrophy (MSA) patients. We examined the role of COQ2 in patients with dementia and essential tremor (ET), two common neurodegenerative conditions. Materials & Methods. A total of 2064 subjects, including 560 patients with dementia, 466 patients with ET, and 1038 healthy controls, were included. Genotyping for the COQ2 V393A (T>C) was carried out. Odds ratio (OR) adjusted by age and gender, together with 95% confidence interval (CI), was reported by means of logistic regression. Results. The frequency of the polymorphic variant V393A heterozygous (T/C) was 2.7% in dementia, 1.1% in ET, and 2.5% in controls (OR = 0.70, 95% confidence interval is 0.29–1.72 for dementia, and OR = 0.47, 95% confidence interval is 0.17–1.31, for ET). There was no significant association between V393A variant with dementia and ET. Conclusion. There was no significant association between V393A variant with dementia and ET. COQ2 gene is unlikely to play a significant role in patients with dementia or ET in our population. Yin Xia Chao, Ebonne Yu Lin Ng, Huihua Li, Kandiah Nagaendran, Yuen Yih, Mei Sian Chong, Kumar M. Prakash, Louis Tan, Wing Lok Au, Yi Zhao, Zhi Dong Zhou, Murni Tio, Ratnagopal Pavanni, and Eng King Tan Copyright © 2015 Yin Xia Chao et al. All rights reserved. The Role of α-Synuclein and LRRK2 in Tau Phosphorylation Tue, 21 Apr 2015 13:17:01 +0000 There is now a considerable body of experimental evidence that Parkinson’s disease arises through physiological interaction of causative molecules, leading to tau pathology. In this review, we discuss the physiological role of α-synuclein and LRRK2 in the abnormal phosphorylation of tau. In addition, as recent reports have indicated that heat shock proteins- (HSPs-) inducing drugs can help to ameliorate neurodegenerative diseases associated with tau pathology, we also discuss therapeutic strategies for PD focusing on inhibition of α-synuclein- and LRRK2-associated tau phosphorylation by HSPs. Fumitaka Kawakami and Takafumi Ichikawa Copyright © 2015 Fumitaka Kawakami and Takafumi Ichikawa. All rights reserved. Neurophysiology of Drosophila Models of Parkinson’s Disease Wed, 15 Apr 2015 12:27:33 +0000 We provide an insight into the role Drosophila has played in elucidating neurophysiological perturbations associated with Parkinson’s disease- (PD-) related genes. Synaptic signalling deficits are observed in motor, central, and sensory systems. Given the neurological impact of disease causing mutations within these same genes in humans the phenotypes observed in fly are of significant interest. As such we observe four unique opportunities provided by fly nervous system models of Parkinson’s disease. Firstly, Drosophila models are instrumental in exploring the mechanisms of neurodegeneration, with several PD-related mutations eliciting related phenotypes including sensitivity to energy supply and vesicular deformities. These are leading to the identification of plausible cellular mechanisms, which may be specific to (dopaminergic) neurons and synapses rather than general cellular phenotypes. Secondly, models show noncell autonomous signalling within the nervous system, offering the opportunity to develop our understanding of the way pathogenic signalling propagates, resembling Braak’s scheme of spreading pathology in PD. Thirdly, the models link physiological deficits to changes in synaptic structure. While the structure-function relationship is complex, the genetic tractability of Drosophila offers the chance to separate fundamental changes from downstream consequences. Finally, the strong neuronal phenotypes permit relevant first in vivo drug testing. Ryan J. H. West, Rebecca Furmston, Charles A. C. Williams, and Christopher J. H. Elliott Copyright © 2015 Ryan J. H. West et al. All rights reserved. Clinical Utility of Skin Biopsy in Differentiating between Parkinson’s Disease and Multiple System Atrophy Mon, 06 Apr 2015 07:56:35 +0000 Background. It is often difficult to differentiate Parkinson’s disease (PD) from multiple system atrophy (MSA), especially in their early stages. Objectives. To examine the clinical utility of histopathological analysis of biopsied skin from the chest wall and/or leg in differentiating between the two diseases. Methods. Skin biopsies from the lower leg and/or anterior chest wall were obtained from 38 patients with idiopathic PD (26 treated with levodopa and 12 levodopa-naïve) and 13 age-matched patients with MSA. We sought aggregates of phosphorylated α-synuclein on cutaneous nerve fibers using double fluorescence immunohistochemistry and confocal microscopy and measured intraepidermal nerve fiber density (IENFD). Results. Phosphorylated α-synuclein aggregates were identified on cutaneous nerves in two patients with PD (5.3%) but in none of the patients with MSA, and IENFD was significantly lower in patients with PD when compared to those with MSA. There was no difference in IENFD between levodopa-treated and levodopa-naïve patients with PD. Conclusions. Our findings suggest that an assessment of IENFD in biopsied skin could be a useful means of differentiating between PD and MSA but that detection of α-synuclein aggregates on cutaneous nerves in the distal sites of the body is insufficiently sensitive. Rie Haga, Kazuhiro Sugimoto, Haruo Nishijima, Yasuo Miki, Chieko Suzuki, Koichi Wakabayashi, Masayuki Baba, Soroku Yagihashi, and Masahiko Tomiyama Copyright © 2015 Rie Haga et al. All rights reserved. Iron Accumulation Is Not Homogenous among Patients with Parkinson’s Disease Sun, 05 Apr 2015 12:44:31 +0000 Background. Iron is considered to lead to neurodegeneration and has been hypothesized as a possible cause of Parkinson’s disease (PD). Susceptibility-weighted imaging (SWI) is a powerful tool to measure phase related iron content of brain. Methods. Twelve de novo patients with PD were recruited from the Movement Disorders Clinic, Department of Neurology, Loma Linda University. Twelve age- and sex-matched non-PD subjects were recruited from neurology clinic as controls. Using SWI, the phase related iron content was estimated from different brain regions of interest (ROIs). Results. There was a trend between increasing age and iron accumulation in the globus pallidus and putamen in all subjects. Iron accumulation was not significant in different ROIs in PD patients compared to controls after adjustment for age. Our data revealed heterogeneity of phase values in different brain ROIs among all subjects with an exaggerated trend at SN in PD patients. Conclusions. Our data suggest a nonhomogeneous pattern of iron accumulation in different brain regions among PD patients. Further studies are needed to explore whether this may correlate to the progression of PD. To our knowledge, this is the first study demonstrating the heterogeneity of iron accumulation in the brain, among patients with PD. Khashayar Dashtipour, Manju Liu, Camellia Kani, Pejman Dalaie, Andre Obenaus, Daniel Simmons, Nicole M. Gatto, and Mehran Zarifi Copyright © 2015 Khashayar Dashtipour et al. All rights reserved. Early Postural Changes in Individuals with Idiopathic Parkinson’s Disease Wed, 01 Apr 2015 14:14:38 +0000 Background and Objectives. Postural changes are frequent and disabling complications of Parkinson’s disease (PD). Many contributing factors have been evident either related to disease pathology or to adaptive changes. This study aimed at studying the postural changes in subjects with Parkinson’s disease and its relation to duration of illness and disease severity. Methods. Eighteen patients with PD and 18 healthy matched volunteers represented the sample of the study. The patients were at stage 1 or 1.5 according to the Modified Hoehn and Yahr Staging with duration of illness between 18 and 36 months. Three-dimensional analysis of the back surface was conducted to explore the postural changes in the sagittal and frontal planes in both the patients and the healthy subjects. Results. Kyphotic angle, lordotic angle, fleche cervicale, fleche lombaire, scoliotic angle, and associated vertebral rotation and pelvic obliquity were significantly increased in patients with PD compared to the healthy subjects (). There was no association between the measured postural changes and duration of illness as well as the severity of the IPD (). Conclusion. Postural changes start in the early stages of idiopathic PD and they have no relationship to the duration of illness and disease severity. Mohamed Elsayed Khallaf and Eman Elsayed Fayed Copyright © 2015 Mohamed Elsayed Khallaf and Eman Elsayed Fayed. All rights reserved. Cognitive Reserve in Parkinson’s Disease: The Effects of Welsh-English Bilingualism on Executive Function Wed, 01 Apr 2015 13:58:15 +0000 Objective. Bilingualism has been shown to benefit executive function (EF) and delay the onset of Alzheimer’s disease. This study aims at examining whether a bilingual advantage applies to EF in Parkinson’s disease (PD). Method. In a cross-sectional outpatient cohort of monolingual English () and bilingual Welsh/English () speakers with PD we evaluated the effects of bilingualism compared with monolingualism on performance on EF tasks. In bilinguals we also assessed the effects of the degree of daily usage of each language and the degree of bilingualism. Results. Monolinguals showed an advantage in performance of language tests. There were no differences in performance of EF tests in monolinguals and bilinguals. Those who used Welsh less in daily life had better performance on one test of English vocabulary. The degree of bilingualism correlated with one test of nonverbal reasoning and one of working memory but with no other tests of EF. Discussion. The reasons why the expected benefit in EF in Welsh-English bilinguals with PD was not found require further study. Future studies in PD should include other language pairs, analysis of the effects of the degree of bilingualism, and longitudinal analysis of cognitive decline or dementia together with structural or functional neuroimaging. John V. Hindle, Pamela A. Martin-Forbes, Alexandra J. M. Bastable, Kirstie L. Pye, Anthony Martyr, Christopher J. Whitaker, Fergus I. M. Craik, Ellen Bialystok, Enlli M. Thomas, Virginia C. Mueller Gathercole, and Linda Clare Copyright © 2015 John V. Hindle et al. All rights reserved. Mitochondrial Dysfunction and -Synuclein Synaptic Pathology in Parkinson’s Disease: Who’s on First? Tue, 31 Mar 2015 08:52:55 +0000 Parkinson’s disease (PD) is the most common neurodegenerative movement disorder. Its characteristic neuropathological features encompass the loss of dopaminergic neurons of the nigrostriatal system and the presence of Lewy bodies and Lewy neurites. These are intraneuronal and intraneuritic proteinaceous insoluble aggregates whose main constituent is the synaptic protein α-synuclein. Compelling lines of evidence indicate that mitochondrial dysfunction and α-synuclein synaptic deposition may play a primary role in the onset of this disorder. However, it is not yet clear which of these events may come first in the sequel of processes leading to neurodegeneration. Here, we reviewed data supporting either that α-synuclein synaptic deposition precedes and indirectly triggers mitochondrial damage or that mitochondrial deficits lead to neuronal dysfunction and α-synuclein synaptic accumulation. The present overview shows that it is still difficult to establish the exact temporal sequence and contribution of these events to PD. Michela Zaltieri, Francesca Longhena, Marina Pizzi, Cristina Missale, PierFranco Spano, and Arianna Bellucci Copyright © 2015 Michela Zaltieri et al. All rights reserved. Progesterone Exerts a Neuromodulatory Effect on Turning Behavior of Hemiparkinsonian Male Rats: Expression of 3α-Hydroxysteroid Oxidoreductase and Allopregnanolone as Suggestive of Receptors Involvement Tue, 31 Mar 2015 08:39:53 +0000 There is a growing amount of evidence for a neuroprotective role of progesterone and its neuroactive metabolite, allopregnanolone, in animal models of neurodegenerative diseases. By using a model of hemiparkinsonism in male rats, injection of the neurotoxic 6-OHDA in left striatum, we studied progesterone’s effects on rotational behavior induced by amphetamine or apomorphine. Also, in order to find potential explanatory mechanisms, we studied expression and activity of nigrostriatal 3α-hydroxysteroid oxidoreductase, the enzyme that catalyzes progesterone to its active metabolite allopregnanolone. Coherently, we tested allopregnanolone for a possible neuromodulatory effect on rotational behavior. Also, since allopregnanolone is known as a modulator, we finally examined the action of antagonist bicuculline. We found that progesterone, in addition to an apparent neuroprotective effect, also increased ipsilateral expression and activity of 3α-hydroxysteroid oxidoreductase. It was interesting to note that ipsilateral administration of allopregnanolone reversed a clear sign of motor neurodegeneration, that is, contralateral rotational behavior. A possible involvement modulated by allopregnanolone was shown by the blocking effect of bicuculline. Our results suggest that early administration of progesterone possibly activates genomic mechanisms that promote neuroprotection subchronically. This, in turn, could be partially mediated by fast, nongenomic, actions of allopregnanolone acting as an acute modulator of GABAergic transmission. Roberto Yunes, Sebastián Casas, Eliana Gaglio, and Ricardo Cabrera Copyright © 2015 Roberto Yunes et al. All rights reserved. The Neuroprotective Mechanism of Low-Frequency rTMS on Nigral Dopaminergic Neurons of Parkinson’s Disease Model Mice Wed, 25 Mar 2015 14:17:16 +0000 Background. Parkinson’s disease is a neurodegenerative disease in elder people, pathophysiologic basis of which is the severe deficiency of dopamine in the striatum. The purpose of the present study was to evaluate the neuroprotective effect of low-frequency rTMS on Parkinson’s disease in model mice. Methods. The effects of low-frequency rTMS on the motor function, cortex excitability, neurochemistry, and neurohistopathology of MPTP-induced Parkinson’s disease mice were investigated through behavioral detection, electrophysiologic technique, high performance liquid chromatography-electrochemical detection, immunohistochemical staining, and western blot. Results. Low-frequency rTMS could improve the motor coordination impairment of Parkinson’s disease mice: the resting motor threshold significantly decreased in the Parkinson’s disease mice; the degeneration of nigral dopaminergic neuron and the expression of tyrosine hydroxylase were significantly improved by low-frequency rTMS; moreover, the expressions of brain derived neurotrophic factor and glial cell line derived neurotrophic factor were also improved by low-frequency rTMS. Conclusions. Low-frequency rTMS had a neuroprotective effect on the nigral dopaminergic neuron which might be due to the improved expressions of brain derived neurotrophic factor and glial cell line-derived neurotrophic factor. The present study provided a theoretical basis for the application of low-frequency rTMS in the clinical treatment and recovery of Parkinson’s disease. Qiaoyun Dong, Yanyong Wang, Ping Gu, Rusheng Shao, Li Zhao, Xiqi Liu, Zhanqiang Wang, and Mingwei Wang Copyright © 2015 Qiaoyun Dong et al. All rights reserved. Monoamine Reuptake Inhibitors in Parkinson’s Disease Wed, 25 Feb 2015 10:36:55 +0000 The motor manifestations of Parkinson’s disease (PD) are secondary to a dopamine deficiency in the striatum. However, the degenerative process in PD is not limited to the dopaminergic system and also affects serotonergic and noradrenergic neurons. Because they can increase monoamine levels throughout the brain, monoamine reuptake inhibitors (MAUIs) represent potential therapeutic agents in PD. However, they are seldom used in clinical practice other than as antidepressants and wake-promoting agents. This review article summarises all of the available literature on use of 50 MAUIs in PD. The compounds are divided according to their relative potency for each of the monoamine transporters. Despite wide discrepancy in the methodology of the studies reviewed, the following conclusions can be drawn: (1) selective serotonin transporter (SERT), selective noradrenaline transporter (NET), and dual SERT/NET inhibitors are effective against PD depression; (2) selective dopamine transporter (DAT) and dual DAT/NET inhibitors exert an anti-Parkinsonian effect when administered as monotherapy but do not enhance the anti-Parkinsonian actions of L-3,4-dihydroxyphenylalanine (L-DOPA); (3) dual DAT/SERT inhibitors might enhance the anti-Parkinsonian actions of L-DOPA without worsening dyskinesia; (4) triple DAT/NET/SERT inhibitors might exert an anti-Parkinsonian action as monotherapy and might enhance the anti-Parkinsonian effects of L-DOPA, though at the expense of worsening dyskinesia. Philippe Huot, Susan H. Fox, and Jonathan M. Brotchie Copyright © 2015 Philippe Huot et al. All rights reserved. The Effects of Uric Acid, Serum Vitamin D3, and Their Interaction on Parkinson’s Disease Severity Tue, 24 Feb 2015 12:42:18 +0000 Objectives. In current study, the relationships between serum vitamin D3 levels and serum UA concentrations as well as their interaction with severity of PD were evaluated in a sample of Iranian PD patients. Method. In a cross sectional study at the one of the main referral hospitals in central region of Iran, during September to November 2011, 112 patients were recruited. Severity of PD was evaluated sing H&R stages and UPDRS. Results. The Spearman rank correlation coefficient suggests the negative significant association between serum vitamin D3 and UPDRS in patients aged >62 (, ). No statistically significant association was observed between the UA levels and severity of PD (represented by H&Y categories) in different levels of serum vitamin D3 not only in total sample but also in separate age and sex groups. The linear regression coefficients suggested positive association between UA and serum vitamin D3 with UPDRSIII scores while negative relationship between UA and serum vitamin D3 interaction with UPDRSIII; however it was only statistically significant in age group ≤62 (). Conclusion. Our study revealed a negative correlation between interaction of serum vitamin D3 and UA with severity of PD; other studies are required to confirm our findings. Rokhsareh Meamar, Pooria Shaabani, Seyed Reza Tabibian, Mohammad Reza Aghaye Ghazvini, and Awat Feizi Copyright © 2015 Rokhsareh Meamar et al. All rights reserved. Transdermal Rotigotine Improves Sleep Fragmentation in Parkinson’s Disease: Results of the Multicenter, Prospective SLEEP-FRAM Study Sun, 22 Feb 2015 12:26:05 +0000 Sleep disturbances occur frequently in patients with Parkinson’s disease (PD). The aim of this study was to investigate the effects of rotigotine on sleep fluctuations in a sample of PD patients with self-reported complaints of nocturnal awakenings. This prospective, open-label, observational, and multicenter study enrolled consecutive outpatients with PD and administered rotigotine (mean dose 8.9 mg/day) for 3 months. The primary endpoint was the change from baseline in sleep fragmentation, assessed using the sleep maintenance subscale score of the Parkinson’s Disease Sleep Scale (PDSS). The newly designed Parkinson’s Disease Sleep Fragmentation Questionnaire (PD-SFQ) was used to measure other sleep parameters. A total of 62 patients were enrolled (mean age 70.2 years; 66% male). At 3 months, rotigotine significantly improved sleep fragmentation from baseline on the PDSS-2 sleep maintenance subscale (from to ; ). Rotigotine also significantly improved nocturnal motor symptoms , restless legs-like symptoms , and nocturia . Rotigotine significantly improved self-reported complaints of sleep fragmentation in PD patients and could be a useful treatment to improve this specific sleep problem in PD. However, these results are based on a small and clinically heterogeneous sample so they must be taken cautiously. Javier Pagonabarraga, Gerard Piñol, Adriana Cardozo, Pilar Sanz, Víctor Puente, Pilar Otermín, Inés Legarda, Tania Delgado, Carmen Serrano, Ernest Balaguer, María Aguirregomozcorta, Ramiro Álvarez, and Jaime J. Kulisevsky Copyright © 2015 Javier Pagonabarraga et al. All rights reserved.