Parkinson’s Disease The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. Evolution of Orofacial Symptoms and Disease Progression in Idiopathic Parkinson’s Disease: Longitudinal Data from the Jönköping Parkinson Registry Sun, 16 Jul 2017 09:21:52 +0000 Background. Orofacial symptoms are common in Parkinson’s disease (PD) both as initial manifestations and late markers of disease complications. We aimed to investigate the evolution of orofacial manifestations and their prognostic value throughout PD progression. Methods. Data was obtained from “Jönköping Parkinson Registry” database on routine care visits of 314 people with idiopathic PD in southern Sweden. Information on baseline symptomatology, orofacial features, UPDRS, and medications was recorded at baseline and during each follow-up visit within an average of 4.2 (range: 1–12) years. Results. Hypomimia, affected speech, drooling, and impaired swallowing were present in 37.3%/91.6%, 14.1%/65.5%, 11.7%/55.3%, and 10.2%/34.5% at baseline/follow-up, respectively. Male sex [OR = 2.4 (95% CI: 1.0–5.9)], UPDRS motor scores [OR = 1.2 (95% CI: 1.1–1.3)], dominant rigidity [OR = 5.2 (95% CI: 1.4–19.1)], and autonomic disturbance [OR = 3.4 (95% CI: 1.1–10.9)] were risk factors for drooling. Individuals with more severe orofacial burden at baseline had shorter median time to develop UPDRS-Part III > 28 [3rd tertile = 4.7 yr, 2nd tertile = 6.2 yr, and 1st tertile = 7.8 yr; p = 0.014]. Conclusions. Majority of people with PD manifest orofacial manifestations at either early or late stages of the disease. PD severity, symmetry of motor disturbances, and autonomic disorders correlate with orofacial symptoms. Individuals with more severe orofacial burden at baseline progressed faster to more advanced stages. Seyed-Mohammad Fereshtehnejad, Örjan Skogar, and Johan Lökk Copyright © 2017 Seyed-Mohammad Fereshtehnejad et al. All rights reserved. Genetic Variants in SNCA and the Risk of Sporadic Parkinson’s Disease and Clinical Outcomes: A Review Tue, 11 Jul 2017 07:12:20 +0000 There is increasing evidence of the contribution of genetic susceptibility to the etiology of Parkinson’s disease (PD). Genetic variations in the SNCA gene are well established by linkage and genome-wide association studies. Positive associations of single nucleotide polymorphisms (SNPs) in SNCA and increased risk for PD were found. However, the role of SNCA variants in individual traits or phenotypes of PD is unknown. Here, we reviewed the current literature and identified 57 studies, performed in fourteen different countries, that investigated SNCA variants and susceptibility to PD. We discussed the findings based on environmental factors, history of PD, clinical outcomes, and ethnicity. In conclusion, SNPs within the SNCA gene can modify the susceptibility to PD, leading to increased or decreased risk. The risk associations of some SNPs varied among samples. Of notice, no studies in South American or African populations were found. There is little information about the effects of these variants on particular clinical aspects of PD, such as motor and nonmotor symptoms. Similarly, evidence of possible interactions between SNCA SNPs and environmental factors or disease progression is scarce. There is a need to expand the clinical applicability of these data as well as to investigate the role of SNCA SNPs in populations with different ethnic backgrounds. Clarissa Loureiro das Chagas Campêlo and Regina Helena Silva Copyright © 2017 Clarissa Loureiro das Chagas Campêlo and Regina Helena Silva. All rights reserved. Deep Brain Stimulation in Parkinson’s Disease: New and Emerging Targets for Refractory Motor and Nonmotor Symptoms Thu, 06 Jul 2017 07:05:45 +0000 Parkinson’s disease (PD) is a progressive neurodegenerative condition characterized by bradykinesia, tremor, rigidity, and postural instability (PI), in addition to numerous nonmotor manifestations. Many pharmacological therapies now exist to successfully treat PD motor symptoms; however, as the disease progresses, it often becomes challenging to treat with medications alone. Deep brain stimulation (DBS) has become a crucial player in PD treatment, particularly for patients who have disabling motor complications from medical treatment. Well-established DBS targets include the subthalamic nucleus (STN), the globus pallidus pars interna (GPi), and to a lesser degree the ventral intermediate nucleus (VIM) of the thalamus. Studies of alternative DBS targets for PD are ongoing, the majority of which have shown some clinical benefit; however, more carefully designed and controlled studies are needed. In the present review, we discuss the role of these new and emerging DBS targets in treating refractory axial motor symptoms and other motor and nonmotor symptoms (NMS). Dustin Anderson, Grayson Beecher, and Fang Ba Copyright © 2017 Dustin Anderson et al. All rights reserved. Deep Brain Stimulation of Hemiparkinsonian Rats with Unipolar and Bipolar Electrodes for up to 6 Weeks: Behavioral Testing of Freely Moving Animals Mon, 03 Jul 2017 08:36:26 +0000 Although the clinical use of deep brain stimulation (DBS) is increasing, its basic mechanisms of action are still poorly understood. Platinum/iridium electrodes were inserted into the subthalamic nucleus of rats with unilateral 6-OHDA-induced lesions of the medial forebrain bundle. Six behavioral parameters were compared with respect to their potential to detect DBS effects. Locomotor function was quantified by (i) apomorphine-induced rotation, (ii) initiation time, (iii) the number of adjusting steps in the stepping test, and (iv) the total migration distance in the open field test. Sensorimotor neglect and anxiety were quantified by (v) the retrieval bias in the corridor test and (vi) the ratio of migration distance in the center versus in the periphery in the open field test, respectively. In our setup, unipolar stimulation was found to be more efficient than bipolar stimulation for achieving beneficial long-term DBS effects. Performance in the apomorphine-induced rotation test showed no improvement after 6 weeks. DBS reduced the initiation time of the contralateral paw in the stepping test after 3 weeks of DBS followed by 3 weeks without DBS. Similarly, sensorimotor neglect was improved. The latter two parameters were found to be most appropriate for judging therapeutic DBS effects. Kathrin Badstuebner, Ulrike Gimsa, Immo Weber, Armin Tuchscherer, and Jan Gimsa Copyright © 2017 Kathrin Badstuebner et al. All rights reserved. Comparison of Globus Pallidus Interna and Subthalamic Nucleus in Deep Brain Stimulation for Parkinson Disease: An Institutional Experience and Review Mon, 19 Jun 2017 06:10:10 +0000 Deep Brain Stimulation (DBS) has revolutionized the lives of patients of Parkinson disease, offering therapeutic options to those not benefiting entirely from medications alone. With its proven track record of outperforming the best medical management, the goal is to unlock the full potential of this therapy. Currently, the Globus Pallidus Interna (GPi) and Subthalamic Nucleus (STN) are both viable targets for DBS, and the choice of site should focus on the constellation of symptoms, both motor and nonmotor, which are key determinants to quality of life. Our article sheds light on the specific advantages and drawbacks of the two sites, highlighting the need for matching the inherent properties of a target with specific desired effects in patients. UT Southwestern Medical Center has a robust and constantly evolving DBS program and the narrative from our center provides invaluable insight into the practical realities of DBS. The ultimate decision in selecting a DBS target is complex, ideally made by a multidisciplinary team, tailored towards each patient’s profile and their expectations, by drawing upon scientific evidence coupled with experience. Ongoing research is expanding our knowledge base, which should be dynamically incorporated into an institute’s DBS paradigm to ensure that patients receive the optimal therapy. Shazia Mirza, Umar Yazdani, Richard Dewey III, Neepa Patel, Richard B. Dewey Jr., Svjetlana Miocinovic, and Shilpa Chitnis Copyright © 2017 Shazia Mirza et al. All rights reserved. Economic Burden Analysis of Parkinson’s Disease Patients in China Wed, 14 Jun 2017 00:00:00 +0000 Background and Objective. Parkinson’s Disease (PD) is a progressive neurodegenerative disorder, which is prevalent in people over 65 years old. PD reduces patients’ quality of life and exerts a heavy economic burden on patients and their families. The purpose of this research is to identify the costs of PD and to evaluate the economic distribution of medical care for PD patients in China. Methods. A professional survey was administered to 116 patients with PD. Records of medical cost were reviewed. Direct and indirect costs were analyzed. The main cost-driving factors of PD were identified using multivariate regression analysis. Results. The average annual cost per PD patient in China is $3,225.94, with direct and indirect costs accounting for $2,503.46 and $722.48, respectively. Direct costs consist of $556.27 for surgery, $44.67 for appointment fees, $605.67 for prescription medication, $460.29 for hospitalization, $71.03 for auxiliary examination, $35.64 for transportation, $10.39 for special equipment, and $719.50 for formal care. The total cost is closely related to surgical treatment, dopamine agonist, and levodopa costs. Conclusion. The cost of PD patients in China is considerable and exceeds average economic capacity, especially antiparkinson medication and caring costs. This study may provide a reference for PD healthcare optimization in the future. Jun-Xiu Yang and Lei Chen Copyright © 2017 Jun-Xiu Yang and Lei Chen. All rights reserved. Does Dopamine Depletion Trigger a Spreader Lexical-Semantic Activation in Parkinson’s Disease? Evidence from a Study Based on Word Fluency Tasks Sun, 11 Jun 2017 00:00:00 +0000 It has been hypothesised that, in Parkinson’s disease (PD), dopamine might modulate spreading activation of lexical-semantic representations. We aimed to investigate this hypothesis in individuals with PD without dementia by assessing word frequency and typicality in verbal fluency tasks. We predicted that the average values of both of these parameters would be lower in PD patients with respect to healthy controls (HC). We administered letter-cued and category-cued fluency tasks to early PD patients in two experimental conditions: the tasks were administered both after 12–18 hours of dopaminergic stimulation withdrawal (“OFF” condition) and after the first daily dose of dopaminergic therapy (“ON” condition). HC were also given the two tasks in two conditions with the same intersession delay as PD patients but without taking drugs. Results showed that in both OFF and ON treatment conditions PD patients did not differ from HC in word frequency or typicality. Moreover, in the PD group, no significant difference was found between the experimental conditions. Our results show that semantic spreading was not altered in the PD sample examined; this suggests that in early PD the functioning of the semantic system is relatively independent from the activity of dopamine brain networks. S. Zabberoni, G. A. Carlesimo, A. Peppe, C. Caltagirone, and A. Costa Copyright © 2017 S. Zabberoni et al. All rights reserved. Subthalamic Nucleus Deep Brain Stimulation in Early Stage Parkinson’s Disease Is Not Associated with Increased Body Mass Index Tue, 06 Jun 2017 07:03:20 +0000 Previous studies suggest that deep brain stimulation of the subthalamic nucleus (STN-DBS) for Parkinson’s disease (PD) leads to weight gain. This study analyzes changes in body mass index (BMI) in 29 subjects from a prospective, single-blind trial of DBS in early stage PD (age 50–75, Hoehn & Yahr stage II off medication, treated with antiparkinsonian medications for ≥6 months but <4 years, and without a history of motor fluctuations, dyskinesias, or dementia). Subjects were randomized to DBS plus optimal drug therapy (DBS+ODT; ) or ODT () and followed for 24 months. Weight and height were recorded at baseline and each follow-up visit and used to calculate BMI. BMIs were compared within and between groups using nonparametric -tests. Mean BMI at baseline was 29.7 in the ODT group and 32.3 in the DBS+ODT group (). BMI change over two years was not different between the groups (, ODT = −0.89; DBS+ODT = −0.17). This study suggests that STN-DBS is not associated with weight gain in subjects with early stage PD. This finding will be tested in an upcoming FDA-approved phase III multicenter, randomized, double-blind, placebo-controlled, pivotal clinical trial evaluating DBS in early stage PD ( identifier NCT00282152). Sarah H. Millan, Mallory L. Hacker, Maxim Turchan, Anna L. Molinari, Amanda D. Currie, and David Charles Copyright © 2017 Sarah H. Millan et al. All rights reserved. Colonic Oxidative and Mitochondrial Function in Parkinson’s Disease and Idiopathic REM Sleep Behavior Disorder Sun, 04 Jun 2017 10:58:32 +0000 Objective. To determine potential mitochondrial and oxidative alterations in colon biopsies from idiopathic REM sleep behavior disorder (iRBD) and Parkinson’s disease (PD) subjects. Methods. Colonic biopsies from 7 iRBD subjects, 9 subjects with clinically diagnosed PD, and 9 healthy controls were homogenized in 5% w/v mannitol. Citrate synthase (CS) and complex I (CI) were analyzed spectrophotometrically. Oxidative damage was assessed either by lipid peroxidation, through malondialdehyde and hydroxyalkenal content by spectrophotometry, or through antioxidant enzyme levels of superoxide dismutase-2 (SOD2), glutathione peroxidase-1 (Gpx1), and catalase (CAT) by western blot. The presence of mitochondrial DNA (mtDNA) deletions was assessed by long PCR and electrophoresis. Results. Nonsignificant trends to CI decrease in both iRBD (; 23% decrease) and PD patients (; 37% decrease) were found compared to controls (, : NS). Lipid peroxidation was maintained among groups (iRBD: , PD: , and controls: ; : NS). Antioxidant enzymes SOD2 (iRBD: , PD: , and controls: ) and Gpx1 (iRBD , PD: , and controls: ) did not show significant differences between groups. CAT was only detected in 2 controls and 1 iRBD subject. One iRBD patient presented a single mtDNA deletion. C. Morén, Í. González-Casacuberta, J. Navarro-Otano, D. Juárez-Flores, D. Vilas, G. Garrabou, J. C. Milisenda, C. Pont-Sunyer, M. Catalán-García, M. Guitart-Mampel, E. Tobías, F. Cardellach, F. Valldeoriola, A. Iranzo, and E. Tolosa Copyright © 2017 C. Morén et al. All rights reserved. Sirtuin-2 Protects Neural Cells from Oxidative Stress and Is Elevated in Neurodegeneration Sun, 28 May 2017 07:26:58 +0000 Sirtuins are highly conserved lysine deacetylases involved in ageing, energy production, and lifespan extension. The mammalian SIRT2 has been implicated in Parkinson’s disease (PD) where studies suggest SIRT2 promotes neurodegeneration. We therefore evaluated the effects of SIRT2 manipulation in toxin treated SH-SY5Y cells and determined the expression and activity of SIRT2 in postmortem brain tissue from patients with PD. SH-SY5Y viability in response to oxidative stress induced by diquat or rotenone was measured following SIRT2 overexpression or inhibition of deacetylase activity, along with α-synuclein aggregation. SIRT2 in human tissues was evaluated using Western blotting, immunohistochemistry, and fluorometric activity assays. In SH-SY5Y cells, elevated SIRT2 protected cells from rotenone or diquat induced cell death and enzymatic inhibition of SIRT2 enhanced cell death. SIRT2 protection was mediated, in part, through elevated SOD2 expression. SIRT2 reduced the formation of α-synuclein aggregates but showed minimal colocalisation with α-synuclein. In postmortem PD brain tissue, SIRT2 activity was elevated compared to controls but also elevated in other neurodegenerative disorders. Results from both in vitro work and brain tissue suggest that SIRT2 is necessary for protection against oxidative stress and higher SIRT2 activity in PD brain may be a compensatory mechanism to combat neuronal stress. Preeti Singh, Peter S. Hanson, and Christopher M. Morris Copyright © 2017 Preeti Singh et al. 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.