Parkinson’s Disease The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. Genetic Profile, Environmental Exposure, and Their Interaction in Parkinson’s Disease Sun, 31 Jan 2016 12:13:07 +0000 The discovery of causative mutations for Parkinson’s disease (PD) as well as their functional characterization in cellular and animal models has provided crucial insight into the pathogenesis of this disorder. Today, we know that PD pathogenesis involves multiple related processes including mitochondrial dysfunction, oxidative and nitrative stress, microglial activation and inflammation, and aggregation of α-synuclein and impaired autophagy. However, with the exception of a few families with Mendelian inheritance, the cause of PD in most individuals is yet unknown and the identified genetic susceptibility factors have only small effect size. Epidemiologic studies have found increased risk of PD associated with exposure to environmental toxicants such as pesticides, organic solvents, metals, and air pollutants, while reduced risk of PD associated with smoking cigarettes and coffee consumption. The role of environmental exposure, as well as the contribution of single genetic risk factors, is still controversial. In most of PD cases, disease onset is probably triggered by a complex interplay of many genetic and nongenetic factors, each of which conveys a minor increase in the risk of disease. This review summarizes the current knowledge on causal mutation for PD, susceptibility factors increasing disease risk, and the genetic factors that modify the impact of environmental exposure. Letizia Polito, Antonio Greco, and Davide Seripa Copyright © 2016 Letizia Polito et al. All rights reserved. Postural Stability in Parkinson’s Disease Patients Is Improved after Stochastic Resonance Therapy Tue, 26 Jan 2016 13:55:57 +0000 Background. Postural instability in Parkinson’s disease (PD) increases the risk of falls and is not improved by pharmacological therapy. Objective. We performed a double-blind, randomized sham-controlled study to test the effects of stochastic resonance (whole body vibration) therapy on postural stability in PD. Methods. Fifty-six PD participants were allocated to either experimental or sham groups. The experimental group received four series of vibration over eight days, with each series consisting of six stimulus trains of 60-second duration using a randomized whole body vibration. Participants allocated to the control group received a sham treatment. Results. Within-group analysis revealed that postural stability in the experimental group improved by 17.5% () comparing experimental and sham groups. The between-group analysis of change after treatment comparing both groups also showed a significant improvement of postural stability (). Only in the within-group analysis several items were improved after Bonferroni correction, too, rigor 41.6% (), bradykinesia 23.7% (), tremor 30.8% (), and sum score 23.9% (), but did not reach the level of significance in the between-group analysis. Conclusions. Stochastic resonance therapy significantly enhanced postural stability even in individuals with increased risk of falling. Thus it offers a potential supplementation to canonical treatments of PD. Oliver Kaut, Daniel Brenig, Milena Marek, Niels Allert, and Ullrich Wüllner Copyright © 2016 Oliver Kaut et al. All rights reserved. Risk Factors of Fatigue in Idiopathic Parkinson’s Disease in a Polish Population Tue, 26 Jan 2016 13:47:48 +0000 Introduction. Fatigue syndrome is one of the nonmotor symptoms in Parkinson’s disease (PD). The aim of the study was assessment of prevalence of fatigue syndrome in PD and answering the question what are the independent risk factors connected with intensity of fatigue in PD. Methods. 114 patients with idiopathic PD (mean age 62.2 + 10.8 years) were enrolled. The fatigue was assessed according to the Fatigue Severity Scale (FSS). We analyzed associations between fatigue and sex, age, education, duration and severity of the disease, everyday activity, intensity of the main symptoms, treatment, presence of dyskinesias and fluctuations, depression and excessive sleep during the day, and presence of pain and nycturia. Results. The fatigue syndrome was detected in 57.9% of patients. The score in the FSS was 1 to 7 points, 4.3 average. Greater fatigue intensity correlated with higher total daily levodopa equivalent dose. Patients with moderate depression had significantly greater fatigue. Conclusions. Fatigue syndrome affects 57.9% of patients with PD. Use of higher LED and presence of moderate depression are independent risk factors of greater intensity of fatigue. Monika Gołąb-Janowska, Dariusz Kotlęga, Krzysztof Safranow, Agnieszka Meller, Anna Budzianowska, and Krystyna Honczarenko Copyright © 2016 Monika Gołąb-Janowska et al. All rights reserved. Variations in Incidence and Prevalence of Parkinson’s Disease in Taiwan: A Population-Based Nationwide Study Tue, 19 Jan 2016 14:15:59 +0000 Demographic, socioeconomic, and urbanization level variations in Parkinson’s disease (PD) are rarely investigated, especially in Asia. This study describes an eight-year trend in PD incidence and prevalence in Taiwan as well as assessing the effects of sociodemographics and urbanization on the incidence and prevalence of PD. The data analyzed were acquired from the Taiwan National Health Insurance Research Database (NHIRD) entries between 2002 and 2009. The calendar year, sex, and age-specific rates were standardized, and the effects of the sociodemographics and urbanization on PD were assessed using Poisson regression analysis. PD incidence and prevalence showed a significantly increasing trend, with a greater magnitude noted for prevalence than for incidence (87.3% versus 9.2%). The PD incidence and prevalence increased with age and were slightly higher in men than in women. The people who were not under the labor force (i.e., dependents) or with lower monthly incomes were at significantly increased adjusted incidence rate ratio (1.50–1.56) and adjusted prevalence rate ratio (1.66–1.71) of PD. Moreover, significantly higher PD incidence and prevalence were noted in areas with lesser urbanization. This information emphasizes the need for preventive and clinical care strategies targeting the segment of Taiwanese population that exhibited a greater incidence and prevalence of PD. Chih-Ching Liu, Chung-Yi Li, Pei-Chen Lee, and Yu Sun Copyright © 2016 Chih-Ching Liu et al. All rights reserved. Clinical Pain and Neuropsychological Functioning in Parkinson’s Disease: Are They Related? Wed, 13 Jan 2016 06:49:27 +0000 Introduction. Pain is an important nonmotor symptom of Parkinson’s disease (PD). Brain areas such as the hippocampus and the prefrontal cortex play an important role in the processing of pain. Since these brain areas are also involved in cognitive functioning, for example, episodic memory and executive functions, respectively, we examined whether a relationship exists between cognitive functioning and spontaneous pain in PD. Methods. Forty-eight patients with PD and 57 controls participated. Cognitive functioning was measured by a comprehensive battery of neuropsychological tests. Both the sensory-discriminative aspect and the motivational-affective aspect of pain were assessed. Multiple linear regression analyses were performed to assess a relation between cognition and pain. Results. Cognition was related to neither the sensory nor the affective aspect of pain in our sample of PD patients. Variance in pain measures was primarily explained by symptoms of depression and anxiety. Discussion. The difference between the affective and the sensory aspect of pain might be due to the neuropathology of PD, which is mainly present in areas processing the affective aspect of pain. Pain treatment might improve when mood is taken into account. We provide several explanations for the lack of an association between pain and cognition. Gwenda Engels, Wouter D. Weeda, Annemarie M. M. Vlaar, Henry C. Weinstein, and Erik J. A. Scherder Copyright © 2016 Gwenda Engels et al. All rights reserved. Abnormal Echogenicity of the Substantia Nigra, Raphe Nuclei, and Third-Ventricle Width as Markers of Cognitive Impairment in Parkinsonian Disorders: A Cross-Sectional Study Sun, 10 Jan 2016 09:44:46 +0000 Background. Patients with Parkinson’s disease (PD) have a high risk of cognitive problems. Objective. This study assesses whether abnormal echogenicity of the substantia nigra (SN) and raphe nuclei (RN) and the diameter of third ventricle are markers of cognitive impairment in patients with PD and other forms of parkinsonism. Methods. 126 outpatients with early signs of parkinsonism underwent transcranial sonography (TCS). The scales for the outcome of Parkinson’s disease cognition (SCOPA-COG) were used as cognitive measure. Definite neurological diagnosis was established after two-year follow-up. Results. One-third of the patients with PD and half of those with APS had signs of cognitive impairment. The echogenicity of the SN was not related to cognitive impairment. The diameter of the third ventricle was significantly larger in PD patients with cognitive impairment compared to those without. In patients with APS we found a significantly higher frequency of hypoechogenic RN in patients with cognitive problems. Conclusions. Cognitive impairment is already present in a substantial proportion of patients with PD and APS at first referral. In patients with APS the frequency of hypoechogenic RN points to the direction of other pathophysiology with more emphasis on deficits in the serotonergic neurotransmitter system. The larger diameter of the third ventricle in PD patients with cognitive impairment may reflect Alzheimer like brain atrophy, as has been reported in earlier studies. Angela E. P. Bouwmans, Albert F. G. Leentjens, Werner H. Mess, and Wim E. J. Weber Copyright © 2016 Angela E. P. Bouwmans et al. All rights reserved. Exposure to Early Life Stress Results in Epigenetic Changes in Neurotrophic Factor Gene Expression in a Parkinsonian Rat Model Sun, 03 Jan 2016 11:08:53 +0000 Early life adversity increases the risk of mental disorders later in life. Chronic early life stress may alter neurotrophic factor gene expression including those for brain derived neurotrophic factor (BDNF) and glial cell derived neurotrophic factor (GDNF) that are important in neuronal growth, survival, and maintenance. Maternal separation was used in this study to model early life stress. Following unilateral injection of a mild dose of 6-hydroxydopamine (6-OHDA), we measured corticosterone (CORT) in the blood and striatum of stressed and nonstressed rats; we also measured DNA methylation and BDNF and GDNF gene expression in the striatum using real time PCR. In the presence of stress, we found that there was increased corticosterone concentration in both blood and striatal tissue. Further to this, we found higher DNA methylation and decreased neurotrophic factor gene expression. 6-OHDA lesion increased neurotrophic factor gene expression in both stressed and nonstressed rats but this increase was higher in the nonstressed rats. Our results suggest that exposure to early postnatal stress increases corticosterone concentration which leads to increased DNA methylation. This effect results in decreased BDNF and GDNF gene expression in the striatum leading to decreased protection against subsequent insults later in life. Thabisile Mpofana, Willie M. U. Daniels, and Musa V. Mabandla Copyright © 2016 Thabisile Mpofana et al. All rights reserved. Foetal Cell Transplantation for Parkinson’s Disease: Focus on Graft-Induced Dyskinesia Thu, 31 Dec 2015 13:36:07 +0000 Transplantation of dopamine- (DA-) rich foetal ventral mesencephalic cells emerged as a promising therapy for Parkinson’s disease (PD), as it allowed significant improvement of motor symptoms in several PD patients in open-label studies. However, double-blind clinical trials have been largely disappointing. The general agreement in the field is that the lack of standardization of tissue collection and preparation, together with the absence of postsurgical immunosuppression, played a key role in the failure of these studies. Moreover, a further complication that emerged in previous studies is the appearance of the so-called graft-induced dyskinesia (GID), in a subset of grafted patients, which resembles dyskinesia induced by L-DOPA but in the absence of medication. Preclinical evidence pointed to the serotonin neurons as possible players in the appearance of GID. In agreement, clinical investigations have shown that grafted tissue may contain a large number of serotonin neurons, in the order of half of the DA cells; moreover, the serotonin 5-HT1A receptor agonist buspirone has been found to produce significant dampening of GID in grafted patients. In this paper, we will review the recent preclinical and clinical studies focusing on cell transplantation for PD and on the mechanisms underlying GID. Elisabetta Tronci, Camino Fidalgo, and Manolo Carta Copyright © 2015 Elisabetta Tronci et al. All rights reserved. Clinical and Epidemiological Factors Associated with Mortality in Parkinson’s Disease in a Brazilian Cohort Sun, 27 Dec 2015 13:32:11 +0000 Background. Prognosis of PD is variable. Most studies show higher mortality rates in PD patients compared to the general population. Clinical and epidemiologic factors predicting mortality are poorly understood. Methods. Clinical and epidemiologic features including patient history and physical, functional, and cognitive scores were collected from a hospital-based cohort of PD patients using standardized protocols and clinical scales. Data on comorbidities and mortality were collected on follow-up. Results. During a mean follow-up of 4.71 years (range 1–10), 43 (20.9%) of the 206 patients died. Those who died had higher mean age at disease onset than those still alive at the last follow-up (67.7 years versus 56.3 years; ). In the univariate analysis, age at baseline was associated with decreased survival. In the adjusted Cox proportional hazards model, age at disease onset and race/ethnicity were predictors of mortality. Conclusions. Late age at disease onset and advanced chronological age are associated with decreased survival. Comorbidities and PD characteristics were not associated with decreased survival in our sample. Race/ethnicity was found in our study to be associated with increased hazard of mortality. Our findings indicate the importance of studying survival among different populations of PD patients. Gustavo Costa Fernandes, Mariana Peixoto Socal, Artur Francisco Schumacher Schuh, and Carlos R. M. Rieder Copyright © 2015 Gustavo Costa Fernandes et al. All rights reserved. Postural and Balance Disorders in Patients with Parkinson’s Disease: A Prospective Open-Label Feasibility Study with Two Months of Action Observation Treatment Tue, 22 Dec 2015 06:38:45 +0000 Action observation treatment has been proposed as therapeutic option in rehabilitation of patients affected by Parkinson’s disease (PD) to improve freezing of gait episodes. The purpose of this prospective open-label feasibility study was to evaluate the impact of 8-week action observation training (video-therapy) for the treatment of postural instability and balance impairment in PD patients. Fifteen PD patients aged under 80 years with scores of 1 to 3 on the Hoehn and Yahr staging and without evidence of freezing of gait were recruited. They underwent 24 sessions of video-therapy training based on carefully watching video clips on motor tasks linked to balance, subsequently performing the same observed movements. No statistically significant differences were observed in the identified outcome measures with the Berg Balance Scale and the Activities-Specific Balance Confidence Scale after two months of follow-up. In the present study, a short course of action observation treatment seems to be not effective in reducing balance impairments and postural instability in patients affected by mild to moderate PD. Further studies with larger samples, longer follow-up period, and standardized protocols of action observation treatment are needed to investigate the effects of this rehabilitation technique in the management of postural and balance disorders of PD patients. Andrea Santamato, Maurizio Ranieri, Nicoletta Cinone, Lucia Anna Stuppiello, Giovanni Valeno, Jula Laura De Sanctis, Francesca Fortunato, Vincenzo Solfrizzi, Antonio Greco, Davide Seripa, and Francesco Panza Copyright © 2015 Andrea Santamato et al. All rights reserved. Rehabilitation Procedures in the Management of Parkinson’s Disease Mon, 21 Dec 2015 11:37:59 +0000 Alessandro Picelli, Talia Herman, Serene S. Paul, and Laurie A. King Copyright © 2015 Alessandro Picelli et al. All rights reserved. Dopaminergic Modulation of Medial Prefrontal Cortex Deactivation in Parkinson Depression Thu, 17 Dec 2015 11:23:53 +0000 Parkinson’s disease (PD) is associated with emotional abnormalities. Dopaminergic medications ameliorate Parkinsonian motor symptoms, but less is known regarding the impact of dopaminergic agents on affective processing, particularly in depressed PD (dPD) patients. The aim of this study was to examine the effects of dopaminergic pharmacotherapy on brain activation to emotional stimuli in depressed versus nondepressed Parkinson disease (ndPD) patients. Participants included 18 ndPD patients (11 men, 7 women) and 10 dPD patients (7 men, 3 women). Patients viewed photographs of emotional faces during functional MRI. Scans were performed while the patient was taking anti-Parkinson medication and the day after medication had been temporarily discontinued. Results indicate that dopaminergic medications have opposite effects in the prefrontal cortex depending upon depression status. DPD patients show greater deactivation in the ventromedial prefrontal cortex (VMPFC) on dopaminergic medications than off, while ndPD patients show greater deactivation in this region off drugs. The VMPFC is in the default-mode network (DMN). DMN activity is negatively correlated with activity in brain systems used for external visual attention. Thus dopaminergic medications may promote increased attention to external visual stimuli among dPD patients but impede normal suppression of DMN activity during external stimulation among ndPD patients. Anders H. Andersen, Charles D. Smith, John T. Slevin, Richard J. Kryscio, Catherine A. Martin, Frederick A. Schmitt, and Lee X. Blonder Copyright © 2015 Anders H. Andersen et al. All rights reserved. Parkinsonian Rigidity Depends on the Velocity of Passive Joint Movement Wed, 16 Dec 2015 14:09:43 +0000 Background. It has been long believed that Parkinsonian rigidity is not velocity-dependent based on the neurological examination. However, this has not been verified scientifically. Methods. The elbow joints of 20 Parkinson’s disease patients were passively flexed and extended, and two characteristic values, the elastic coefficient (elasticity) and the difference in bias (difference in torque measurements for extension and flexion), were identified from a plot of the angle and torque characteristics. Flexion and extension were done at two different velocities, 60°/s and 120°/s, and a statistical analysis was performed to determine whether the changes in these characteristic values were velocity-dependent. Results. The elastic coefficient was not velocity-dependent, but the difference in bias increased in a velocity-dependent manner (). Conclusions. The features of rigidity may differ from the conventional definition, which states that they are not dependent on the velocity of joint movement. Takuyuki Endo, Naoya Yoshikawa, Harutoshi Fujimura, and Saburo Sakoda Copyright © 2015 Takuyuki Endo et al. All rights reserved. Association of a BACE1 Gene Polymorphism with Parkinson’s Disease in a Norwegian Population Mon, 14 Dec 2015 12:55:17 +0000 Background. Parkinson’s disease (PD) and Alzheimer’s disease (AD) share pathological features, including amyloid-beta pathology. Amyloid-beta peptide is generated by sequential proteolysis of amyloid precursor protein (APP), and genetic variations in the processing pathway genes have been found to increase the risk of AD; however, the contribution in PD is unknown. Methods. The aim of this study was to investigate whether candidate polymorphisms in five genes (ADAM10, BACE1, BACE2, PSEN2, and CLU) involved in the APP processing pathway affect PD risk in a population-based cohort of patients with incident PD and control subjects from the Norwegian ParkWest study. Results. We found an association of rs638405 in BACE1 with increased risk of PD, thus providing a novel link, at the genetic level, between amyloid-beta pathology and PD. Johannes Lange, Kristin Aaser Lunde, Camilla Sletten, Simon Geir Møller, Ole-Bjørn Tysnes, Guido Alves, Jan Petter Larsen, and Jodi Maple-Grødem Copyright © 2015 Johannes Lange et al. All rights reserved. Sleep Problems in Parkinson’s Disease Mon, 14 Dec 2015 06:57:48 +0000 Koichi Hirata, Birgit Högl, Eng King Tan, and Aleksandar Videnovic Copyright © 2015 Koichi Hirata et al. All rights reserved. EGCG Protects against 6-OHDA-Induced Neurotoxicity in a Cell Culture Model Sun, 06 Dec 2015 14:03:25 +0000 Background. Parkinson’s disease (PD) is a progressive neurodegenerative disease that causes severe brain dopamine depletion. Disruption of iron metabolism may be involved in the PD progression. Objective. To test the protective effect of (−)-epigallocatechin-3-gallate (EGCG) against 6-hydroxydopamine- (6-OHDA-) induced neurotoxicity by regulating iron metabolism in N27 cells. Methods. Protection by EGCG in N27 cells was assessed by SYTOX green assay, MTT, and caspase-3 activity. Iron regulatory gene and protein expression were measured by RT-PCR and Western blotting. Intracellular iron uptake was measured using 55Fe. The EGCG protection was further tested in primary mesencephalic dopaminergic neurons by immunocytochemistry. Results. EGCG protected against 6-OHDA-induced cell toxicity. 6-OHDA treatment significantly () increased divalent metal transporter-1 (DMT1) and hepcidin and decreased ferroportin 1 (Fpn1) level, whereas pretreatment with EGCG counteracted the effects. The increased 55Fe (by 96%, ) cell uptake confirmed the iron burden by 6-OHDA and was reduced by EGCG by 27% (), supporting the DMT1 results. Pretreatment with EGCG and 6-OHDA significantly increased () TH+ cell count (~3-fold) and neurite length (~12-fold) compared to 6-OHDA alone in primary mesencephalic neurons. Conclusions. Pretreatment with EGCG protected against 6-OHDA-induced neurotoxicity by regulating genes and proteins involved in brain iron homeostasis, especially modulating hepcidin levels. Dan Chen, Anumantha G. Kanthasamy, and Manju B. Reddy Copyright © 2015 Dan Chen et al. All rights reserved. Diffusion Kurtosis Imaging of Substantia Nigra Is a Sensitive Method for Early Diagnosis and Disease Evaluation in Parkinson’s Disease Thu, 03 Dec 2015 11:38:15 +0000 Background. To diagnose Parkinson disease (PD) in an early stage and accurately evaluate severity, it is important to develop a sensitive method for detecting structural changes in the substantia nigra (SN). Method. Seventy-two untreated patients with early PD and 72 healthy controls underwent diffusion tensor and diffusion kurtosis imaging. Regions of interest were drawn in the rostral, middle, and caudal SN by two blinded and independent raters. Mean kurtosis (MK) and fractional anisotropy in the SN were compared between the groups. Receiver operating characteristic (ROC) and Spearman correlation analyses were used to compare the diagnostic accuracy and correlate imaging findings with Hoehn-Yahr (H-Y) staging and part III of the Unified Parkinson’s Disease Rating Scale (UPDRS-III). Result. MK in the SN was increased significantly in PD patients compared with healthy controls. The area under the ROC curve was 0.976 for MK in the SN (sensitivity, 0.944; specificity, 0.917). MK in the SN had a positive correlation with H-Y staging and UPDRS-III scores. Conclusion. Diffusion kurtosis imaging is a sensitive method for PD diagnosis and severity evaluation. MK in the SN is a potential biomarker for imaging studies of early PD that can be widely used in clinic. Guohua Zhang, Yuhu Zhang, Chengguo Zhang, Yukai Wang, Guixian Ma, Kun Nie, Haiqun Xie, Jianping Liu, and Lijuan Wang Copyright © 2015 Guohua Zhang et al. All rights reserved. Medical Record Review to Differentiate between Idiopathic Parkinson’s Disease and Parkinsonism: A Danish Record Linkage Study with 10 Years of Follow-Up Thu, 03 Dec 2015 11:08:17 +0000 Background. The electronic medical records provide new and unprecedented opportunities for large population-based and clinical studies if valid and reliable diagnoses can be obtained, to determine what information is needed to distinguish idiopathic PD from Parkinsonism in electronic medical records. Methods. Chart review of complete medical records of 2,446 patients with a hospital discharge diagnosis of PD, who, between 1996 and 2009, were registered in the Danish National Hospital Register as idiopathic PD. All patients were examined in neurology departments. Clinical features were abstracted from charts to determine Parkinsonian phenotypes and disease course, using predefined criteria for idiopathic PD. Results. Chart review verified that 2,068 (84.5%) patients met criteria for idiopathic PD. The most distinguishing features of idiopathic PD patients were asymmetric onset, and fewer atypical features at onset or follow-up compared to Parkinsonism, and the area under the curve (AUC) for these items alone is moderate (0.74–0.77) and the highest AUC (0.91) was achieved when using all clinical features recorded in addition to PD medication use and a follow-up of 5 years or more. Conclusion. To reduce disease misclassification, information extracted from medical record review with at least 5 years of follow-up after first diagnosis was key to improve diagnostic accuracy. Lene Wermuth, Xin Cui, Naomi Greene, Eva Schernhammer, and Beate Ritz Copyright © 2015 Lene Wermuth et al. All rights reserved. Rapid Screening for Cognitive Impairment in Parkinson’s Disease: A Pilot Study Wed, 02 Dec 2015 11:50:58 +0000 Aim. This study sought to establish the discriminant validity of a rapid cognitive screen, that is, the National Institute of Neurological Disease and Stroke-Canadian Stroke Network (NINDS-CSN) 5-minute protocol, and compare its discriminant validity to the Montreal Cognitive Assessment (MoCA) and Mini Mental State Examination (MMSE) in detecting cognitive impairment (CI) in PD patients. Methods. One hundred and one PD patients were recruited from a movement disorders clinic in Singapore and they received the NINDS-CSN 5-minute protocol, MoCA, and MMSE. No cognitive impairment (NCI) was defined as Clinical Dementia Rating (CDR) = 0 and CI was defined as CDR ≥ 0.5. Results. Area under the receiver operating characteristic curve of NINDS-CSN 5-minute protocol was statistically equivalent to MoCA and larger than MMSE (0.86 versus 0.90, ; 0.86 versus 0.76, ). The sensitivity of NINDS-CSN 5-minute protocol (<9) was statistically equivalent to MoCA (<22) (0.77 versus 0.85, ) and superior to MMSE (<24) (0.77 versus 0.52, ) in detecting CI, while the specificity of NINDS-CSN 5-minute protocol (<9) was statistically equivalent to MoCA (<22) and MMSE (<24) (0.78 versus 0.88, ). Conclusion. The NINDS-CSN 5-minute protocol is time expeditious while remaining statistically equivalent to MoCA and superior to MMSE and therefore is suitable for rapid cognitive screening of CI in PD patients. YanHong Dong, Way Inn Koay, Leonard Leong Litt Yeo, Christopher Li-Hsian Chen, Jing Xu, Raymond Chee Seong Seet, and Erle Chuen Hian Lim Copyright © 2015 YanHong Dong et al. All rights reserved. The Influence of Parkinson’s Disease Motor Symptom Asymmetry on Hand Performance: An Examination of the Grooved Pegboard Task Thu, 26 Nov 2015 12:00:55 +0000 This study examined the influence of motor symptom asymmetry in Parkinson’s disease (PD) on Grooved Pegboard (GP) performance in right-handed participants. The Unified Parkinson’s Disease Rating Scale was used to assess motor symptoms and separate participants with PD into two groups (right-arm affected, left-arm affected) for comparison with a group of healthy older adults. Participants completed the place and replace GP tasks two times with both hands. Laterality quotients were computed to quantify performance differences between the two hands. Comparisons among the three groups indicated that when the nonpreferred hand is affected by PD motor symptoms, superior preferred hand performance (as seen in healthy older adults) is further exaggerated in tasks that require precision (i.e., place task). Regardless of the task, when the preferred hand is affected, there is an evident shift to superior left-hand performance, which may inevitably manifest as a switch in hand preference. Results add to the discussion of the relationship between handedness and motor symptom asymmetry in PD. Sara M. Scharoun, Pamela J. Bryden, Michael D. Sage, Quincy J. Almeida, and Eric A. Roy Copyright © 2015 Sara M. Scharoun et al. All rights reserved. Acute and Chronic Effect of Acoustic and Visual Cues on Gait Training in Parkinson’s Disease: A Randomized, Controlled Study Thu, 26 Nov 2015 06:49:17 +0000 In this randomized controlled study we analyse and compare the acute and chronic effects of visual and acoustic cues on gait performance in Parkinson’s Disease (PD). We enrolled 46 patients with idiopathic PD who were assigned to 3 different modalities of gait training: (1) use of acoustic cues, (2) use of visual cues, or (3) overground training without cues. All patients were tested with kinematic analysis of gait at baseline (T0), at the end of the 4-week rehabilitation programme (T1), and 3 months later (T2). Regarding the acute effect, acoustic cues increased stride length and stride duration, while visual cues reduced the number of strides and normalized the stride/stance distribution but also reduced gait speed. As regards the chronic effect of cues, we recorded an improvement in some gait parameters in all 3 groups of patients: all 3 types of training improved gait speed; visual cues also normalized the stance/swing ratio, acoustic cues reduced the number of strides and increased stride length, and overground training improved stride length. The changes were not retained at T2 in any of the experimental groups. Our findings support and characterize the usefulness of cueing strategies in the rehabilitation of gait in PD. Roberto De Icco, Cristina Tassorelli, Eliana Berra, Monica Bolla, Claudio Pacchetti, and Giorgio Sandrini Copyright © 2015 Roberto De Icco et al. All rights reserved. Knowledge and Attitudes of Parkinson’s Disease in Rural and Urban Mukono District, Uganda: A Cross-Sectional, Community-Based Study Wed, 25 Nov 2015 06:47:27 +0000 Background. Parkinson’s disease (PD) negatively affects the quality of life. There is limited information on PD published from Africa. Lack of adequate knowledge poses a barrier in the provision of appropriate treatment and care for individuals with PD. Methods. A cross-sectional survey was conducted in urban and rural Mukono district, central Uganda. Through the systematic sampling method, data were gathered from 377 adult participants, interviewed on selected aspects of PD knowledge and attitudes. Results. Of the 377 participants, 47% were from urban settings and 68% (260/377) were women with a median age (IQR) of 34 (26–48) years. Half of the study respondents did not know the body part involved in or apparent cause of PD. Nearly 1/3 of individuals believed that PD is a form of insanity and 17% believed that PD is contagious. Rural dwellers were more likely to have incorrect knowledge regarding selected aspects of PD. Conclusions. Understanding the cause of PD is very limited in our setting. Some beliefs about PD aetiology may potentially worsen stigma and social isolation. This study highlights the need for increasing PD awareness in our settings. Public health approaches that improve knowledge are urgently needed to promote care access and community response to Parkinson’s disease. Mark Kaddumukasa, Angelina Kakooza, Martin N. Kaddumukasa, Edward Ddumba, Levi Mugenyi, Martha Sajatovic, and Elly Katabira Copyright © 2015 Mark Kaddumukasa et al. All rights reserved. Pisa Syndrome in Parkinson’s Disease: Electromyographic Aspects and Implications for Rehabilitation Mon, 23 Nov 2015 11:20:37 +0000 Pisa Syndrome (PS) is a real clinical enigma, and its management remains a challenge. In order to improve the knowledge about resting state and during maximal voluntary muscle contraction (MVMC) of the axial muscles, we described the electromyography results of paraspinal muscles, rectus abdominis, external oblique, and quadratus lumborum of both sides of 60 patients. Electromyography was assessed at rest, during MVMC while bending in the opposite direction of the PS and during MVMC while bending in the direction of the PS. The MVMC gave information about the interferential pattern (INT) or subinterferential pattern (sub-INT). We defined asymmetrical activation (AA) when a sub-INT was detected on the muscle on the side opposite to the PS bending and an INT of same muscle in the direction of PS bending. We observed significant AA during MVMC only in the external oblique muscles in 78% of the subjects. Our results of asymmetric ability to generate maximal voluntary force of the external oblique muscles support a central dissynchronisation of axial muscles as a significant contributor for the bending of the spine in erect position. These results could have important implication to physiotherapy and the use of botulinum toxin in the treatment of PS. Giuseppe Frazzitta, Pietro Balbi, Francesco Gotti, Roberto Maestri, Annarita Sabetta, Luca Caremani, Laura Gobbi, Marina Capobianco, Rossana Bera, Nir Giladi, and Davide Ferrazzoli Copyright © 2015 Giuseppe Frazzitta et al. All rights reserved. Impact of Impulse Control Disorders on Sleep-Wake Regulation in Parkinson’s Disease Wed, 18 Nov 2015 11:52:05 +0000 Sleep disturbances are common in patients with Parkinson’s disease (PD) and are even more prevalent in patients with behavioural addictions, such as pathological gambling, compulsive sexual behaviour, compulsive buying, binge eating, punding, and the compulsive use of dopamine replacement therapy. An overview of the relationship between these impulse control disorders and sleep disturbances is given and potential underlying mechanisms and treatment strategies are covered. Atbin Djamshidian, Werner Poewe, and Birgit Högl Copyright © 2015 Atbin Djamshidian et al. All rights reserved. Enhanced Neuroprotective Effects of Coadministration of Tetrandrine with Glutathione in Preclinical Model of Parkinson’s Disease Wed, 18 Nov 2015 09:16:37 +0000 Aim. In this study we examined the influence of tetrandrine (Tet) on the neuroprotective effects of glutathione (GSH) in the 6-hydroxydopamine- (6-OHDA-) lesioned rat model of Parkinson’s disease (PD). Methods. Levels in the redox system, dopamine (DA) metabolism, dopaminergic neuronal survival, and apoptosis of the substantia nigra (SN) and striatum, as well as the rotational behavior of animals were examined after a 50-day administration of GSH + Tet (or GSH) and/or L-3,4-dihydroxyphenylalanine (L-dopa) to PD rats. Ethics Committee of Huashan Hospital, Fudan University approved the protocol (number SYXK2009-0082). Results. Administration of GSH or Tet alone did not show any significant effects on the factors evaluated in the PD rats. However, in the GSH + Tet group, we observed markedly decreased oxidative damage, inhibition of DA metabolism and enhanced DA synthesis, increased tyrosine hydroxylase- (TH-) immunopositive neuronal survival, and delayed apoptosis of dopaminergic neurons in the SN. Animal rotational behavior was improved in the GSH + Tet group. Additionally, coadministration of GSH + Tet appeared to offset the possible oxidative neurotoxicity induced by L-dopa. Conclusion. In this study, we demonstrated that tetrandrine allowed occurrence of the neuroprotective effect of glutathione probably due to inhibition of P-glycoprotein on 6-hydroxydopamine-lesioned rat models of Parkinson’s disease, including rats undergoing long-term L-dopa treatment. Xiang-Yun Li, Guang-Hai Mei, Qiang Dong, Yu Zhang, Zhuang-Li Guo, Jing-Jing Su, Yu-Ping Tang, Xue-Hong Jin, Hou-Guang Zhou, and Yan-Yan Huang Copyright © 2015 Xiang-Yun Li et al. All rights reserved. Potential of Neural Stem Cell-Based Therapy for Parkinson’s Disease Tue, 17 Nov 2015 13:19:34 +0000 Neural stem cell (NSC) transplantation is an emerging strategy for restoring neuronal function in neurological disorders, such as Parkinson’s disease (PD), which is characterized by a profound and selective loss of nigrostriatal dopaminergic (DA) neurons. Adult neurogenesis generates newborn neurons that can be observed at specialized niches where endothelial cells (ECs) play a significant role in regulating the behavior of NSCs, including self-renewal and differentiating into all neural lineage cells. In this minireview, we highlight the importance of establishing an appropriate microenvironment at the target site of NSC transplantation, where grafted cells integrate into the surroundings in order to enhance DA neurotransmission. Using a novel model of NSC-EC coculture, it is possible to combine ECs with NSCs, to generate such a neurovascular microenvironment. With appropriate NSCs selected, the composition of the transplant can be investigated through paracrine and juxtacrine signaling within the neurovascular unit (NVU). With target site cellular and acellular compartments of the microenvironment recognized, guided DA differentiation of NSCs can be achieved. As differentiated DA neurons integrate into the existing nigrostriatal DA pathway, the symptoms of PD can potentially be alleviated by reversing characteristic neurodegeneration. Chung-Hsing Chou, Hueng-Chuen Fan, and Dueng-Yuan Hueng Copyright © 2015 Chung-Hsing Chou et al. All rights reserved. Myocardial 123I-MIBG Uptake and Cardiovascular Autonomic Function in Parkinson’s Disease Sun, 15 Nov 2015 10:00:32 +0000 Introduction. Patients with Parkinson’s disease (PD) showed reduced myocardial 123I-MIBG uptake, which may affect autonomic regulation. We investigated correlation between MIBC accumulation and cardiovascular autonomic function in PD. Methods. We performed myocardial MIBG scintigraphy, heart rate variability (HRV) analysis, and the head-up tilt test (HUT) in 50 PD patients ( years; duration years). Autonomic function tests were also performed in 50 healthy controls ( years). As HRV parameters, a high-frequency power (HF, 0.15–0.4 Hz), a low-frequency power (LF, 0.04–0.15 Hz), and LF/HF ratio were used. Results. Our PD patients had a significant reduction in LF and HF compared with the controls ( and ). In HUT, systolic and diastolic blood pressure falls in the PD group were significantly greater than those in the controls ( and ). The washout rate of MIBG was negatively correlated with blood pressure changes during HUT. Conclusion. Our PD patients showed reduced HRV, blood pressure dysregulation, and reduced MIBG accumulation, which was correlated with blood pressure dysregulation. Orthostatic hypotension in PD may be mainly caused by sympathetic postganglionic degeneration. Akira Katagiri, Masato Asahina, Nobuyuki Araki, Anupama Poudel, Yoshikatsu Fujinuma, Yoshitaka Yamanaka, and Satoshi Kuwabara Copyright © 2015 Akira Katagiri et al. All rights reserved. Impact of Deep Brain Stimulation on Daily Routine Driving Practice in Patients with Parkinson’s Disease Tue, 10 Nov 2015 14:26:54 +0000 Objective. To determine the influence of deep brain stimulation (DBS) on daily routine driving behavior in Parkinson’s disease (PD) patients. Methods. A cross-sectional questionnaire survey was done in 121 DBS-PD patients. The influences of patient characteristics and DBS on current driving and driving at time of surgery and the predictive value of the preoperative levodopa-test on postoperative driving were evaluated. Results. 50% of 110 driving-license holders currently drove. 63.0% rated themselves as safe drivers, 39.4% reported improvement, and 10.9% noted deterioration in driving after DBS surgery. Inactive drivers had quit driving mainly due to disease burden (90.9%). Active drivers were younger, more often males, and less impaired according to H&Y and MMSE, had surgery more recently, and reported more often overall benefit from DBS. H&Y “on” and UPDRS III “off” scores at time of surgery were lower in pre- and postoperative active than in inactive drivers. Tremor and akinesia were less frequent reasons to quit driving after than before DBS surgery. Postoperatively, 22.7% (10/44) of patients restarted and 10.6% (7/66) of patients discontinued driving, independently of H&Y stage. The preoperative levodopa-test was not predictive for the postoperative driving outcome. Conclusion. 50% of PD patients with DBS drive. DBS surgery changes daily routine driving behavior. Carsten Buhmann, Eik Vettorazzi, Christian Oehlwein, Fred Rikkers, Monika Poetter-Nerger, Alessandro Gulberti, Christian Gerloff, Christian K. Moll, and Wolfgang Hamel Copyright © 2015 Carsten Buhmann et al. All rights reserved. Four Copies of SNCA Responsible for Autosomal Dominant Parkinson’s Disease in Two Italian Siblings Mon, 09 Nov 2015 09:26:33 +0000 Background. Parkinson’s disease (PD) is mostly characterized by alpha-synuclein (SNCA) aggregation and loss of nigrostriatal dopamine-containing neurons. In this study a novel SNCA multiplication is described in two siblings affected by severe parkinsonism featuring early onset dyskinesia, psychiatric symptoms, and cognitive deterioration. Methods. SNCA dosage was performed using High-Density Comparative Genomic Hybridization Array (CGH-Array), Multiple Ligation Dependent Probe Amplification (MLPA), and Quantitative PCR (qPCR). Genetic analysis was associated with clinical evaluation. Results. Genetic analysis of siblings showed for the first time a 351 Kb triplication containing SNCA gene along with 6 exons of MMRN1 gene in 4q22.1 and a duplication of 1,29 Mb of a genomic region flanking the triplication. Conclusions. The identification of this family indicates a novel mechanism of SNCA gene multiplication, which confirms the genomic instability in this region and provides data on the genotype-phenotype correlation in PD patients. Rosangela Ferese, Nicola Modugno, Rosa Campopiano, Marco Santilli, Stefania Zampatti, Emiliano Giardina, Annamaria Nardone, Diana Postorivo, Francesco Fornai, Giuseppe Novelli, Edoardo Romoli, Stefano Ruggieri, and Stefano Gambardella Copyright © 2015 Rosangela Ferese et al. All rights reserved. Screening for Mild Cognitive Impairment in Parkinson’s Disease: Comparison of the Italian Versions of Three Neuropsychological Tests Sun, 08 Nov 2015 10:00:29 +0000 Mild cognitive impairment (MCI) is frequent in Parkinson’s disease (PD). Recently proposed criteria for MCI in PD (PD-MCI) indicate level I diagnosis based on abbreviated assessment and level II based on comprehensive neuropsychological evaluation. The study explored the sensitivity and specificity of the Italian versions of three neuropsychological tests for level I diagnosis of PD-MCI. We recruited 100 consecutive PD patients. After screening for inclusion criteria, 43 patients were included. The sensitivity and specificity of the Mini Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), and the Addenbrooke’s Cognitive Examination Revised (ACE-R) in comparison to level II diagnosis of PD-MCI were examined. PD-MCI was diagnosed (level II) in 51% of patients. Disease duration was significantly longer and PD motor scales were more severely impaired in MCI group. The receiver-operator characteristics curve documented nonsignificant difference in the performance of the three tests, with slight advantage of MMSE (corrected data). The time of administration favored MMSE. In Italian-speaking PD patients, MMSE might represent a good screening tool for PD-MCI, because of the shorter time of administration and the performance comparable to those of MoCA and ACE-R. Further studies are needed to validate the new PD-MCI criteria across different languages and cultures. Angela Federico, Alice Maier, Greta Vianello, Daniela Mapelli, Michela Trentin, Giampietro Zanette, Alessandro Picelli, Marialuisa Gandolfi, and Stefano Tamburin Copyright © 2015 Angela Federico et al. All rights reserved.