Parkinson’s Disease The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Parkinson’s Disease Prevalence and Proximity to Agricultural Cultivated Fields Tue, 18 Aug 2015 16:10:13 +0000 The risk for developing Parkinson’s disease (PD) is a combination of multiple environmental and genetic factors. The Negev (Southern Israel) contains approximately 252.5 km2 of agricultural cultivated fields (ACF). We aimed to estimate the prevalence and incidence of PD and to examine possible geographical clustering and associations with agricultural exposures. We screened all “Clalit” Health Services members in the Negev (70% of the population) between the years 2000 and 2012. Individual demographic, clinical, and medication prescription data were available. We used a refined medication tracer algorithm to identify PD patients. We used mixed Poisson models to calculate the smoothed standardized incidence rates (SIRs) for each locality. We identified ACF and calculate the size and distance of the fields from each locality. We identified 3,792 cases of PD. SIRs were higher than expected in Jewish rural localities (median SIR [95% CI]: 1.41 [1.28; 1.53] in 2001–2004, 1.62 [1.48; 1.76] in 2005–2008, and 1.57 [1.44; 1.80] in 2009–2012). Highest SIR was observed in localities located in proximity to large ACF (SIR 1.54, 95% CI 1.32; 1.79). In conclusion, in this population based study we found that PD SIRs were higher than expected in rural localities. Furthermore, it appears that proximity to ACF and the field size contribute to PD risk. Maayan Yitshak Sade, Yair Zlotnik, Itai Kloog, Victor Novack, Chava Peretz, and Gal Ifergane Copyright © 2015 Maayan Yitshak Sade et al. All rights reserved. Changes to Intermediary Metabolites in Sporadic and LRRK2 Parkinson’s Disease Demonstrated by Proton Magnetic Resonance Spectroscopy Tue, 18 Aug 2015 14:32:50 +0000 Background. Parkinson’s disease (PD) remains a clinical diagnosis and biomarkers are needed to detect the disease as early as possible. Genetically determined PD provides an opportunity for studying metabolic differences in connection with disease development. Objectives. To study the levels of intermediary metabolites in cerebrospinal fluid (CSF) from patients with PD, either of sporadic type or in carriers of the LRRK2 p.G2019S mutation. Methods. Results from patients with sporadic PD or LRRK2-PD were compared with asymptomatic LRRK2 mutation carriers and healthy control individuals. CSF was analysed by proton MR spectroscopy (1H-MRS) giving reliable results for 16 intermediary metabolites. Partial least squares discriminant analysis (PLS-DA) was applied to study group differences. Results. PLS-DA distinguished PD patients from healthy individuals based on the metabolites identified in CSF, with 2-hydroxybutyrate, glutamine, and dimethyl sulphone largely contributing to the separations. Conclusion. Speculatively, all three metabolites could alter concentration in response to metabolic changes connected with neurodegeneration; glutamine as a means of removing excess nitrogen from brain, dimethyl sulphone as an anti-inflammatory agent, and 2-hydroxybutyrate in connection with altered glutathione metabolism. Potentially, 1H-MRS is a promising tool for identifying novel biomarkers for PD. Jan O. Aasly, Oddbjørn Sæther, Krisztina K. Johansen, Tone F. Bathen, Guro F. Giskeødegård, and Linda R. White Copyright © 2015 Jan O. Aasly et al. All rights reserved. Addenbrooke’s Cognitive Examination and Individual Domain Cut-Off Scores for Discriminating between Different Cognitive Subtypes of Parkinson’s Disease Mon, 17 Aug 2015 09:50:37 +0000 Objective. The main aim of this study was to verify the sensitivity and specificity of Addenbrooke’s Cognitive Examination-Revised (ACE-R) in discriminating between Parkinson’s disease (PD) with normal cognition (PD-NC) and PD with mild cognitive impairment (PD-MCI) and between PD-MCI and PD with dementia (PD-D). We also evaluated how ACE-R correlates with neuropsychological cognitive tests in PD. Methods. We examined three age-matched groups of PD patients diagnosed according to the Movement Disorder Society Task Force criteria: PD-NC, PD-MCI, and PD-D. ROC analysis was used to establish specific cut-off scores of ACE-R and its domains. Correlation analyses were performed between ACE-R and its subtests with relevant neuropsychological tests. Results. Statistically significant differences between groups were demonstrated in global ACE-R scores and subscores, except in the language domain. ACE-R cut-off score of 88.5 points discriminated best between PD-MCI and PD-NC (sensitivity 0.68, specificity 0.91); ACE-R of 82.5 points distinguished best between PD-MCI and PD-D (sensitivity 0.70, specificity 0.73). The verbal fluency domain of ACE-R demonstrated the best discrimination between PD-NC and PD-MCI (cut-off score 11.5; sensitivity 0.70, specificity 0.73) while the orientation/attention subscore was best between PD-MCI and PD-D (cut-off score 15.5; sensitivity 0.90, specificity 0.97). ACE-R scores except for ACE-R language correlated with specific cognitive tests of interest. Dagmar Berankova, Eva Janousova, Martina Mrackova, Ilona Eliasova, Milena Kostalova, Svetlana Skutilova, and Irena Rektorova Copyright © 2015 Dagmar Berankova et al. All rights reserved. Interleukin-6 May Contribute to Mortality in Parkinson’s Disease Patients: A 4-Year Prospective Study Sun, 16 Aug 2015 13:29:02 +0000 Objectives. The association between abnormal serum immunomarkers and mortality in 53 consecutive Parkinson’s disease patients was studied. Materials and Methods. The plasma level of specific inflammatory cytokines was investigated: mannan-binding lectin (MBL), interleukin- (IL-) 6, and tumor necrosis factor-alpha (TNF-α). The baseline serum immunomarkers obtained from patients who died () during a four-year follow-up period were compared with the data of patients who survived (). Results. The baseline level of IL-6 was significantly higher in the deceased patients than in the survivors. Elevated IL-6 levels and age were major independent contributors to disease mortality. Differences between other plasma cytokine level abnormalities were not significant. Conclusion. This study showed that IL-6 elevation may be a marker of increased mortality risk in Parkinson’s disease patients. The inflammation may act in association with other factors and comorbidities in progressive neurodegenerative pathology. Michal Dufek, Irena Rektorova, Vojtech Thon, Jindrich Lokaj, and Ivan Rektor Copyright © 2015 Michal Dufek et al. All rights reserved. Relationship between Postural Deformities and Frontal Function in Parkinson’s Disease Thu, 13 Aug 2015 12:29:24 +0000 Postural deformities and executive dysfunction (ED) are common symptoms of Parkinson’s disease (PD); however, the relationship between postural deformities and ED in patients with PD remains unclear. This study assessed the relationship between postural deformities and ED in patients with PD. Sixty-five patients with sporadic PD were assessed for the severity of postural deformities and executive function. The severity of postural deformities was scored using the United Parkinson’s Disease Rating Scale item 28 score: no postural deformity (0), mild postural deformities (1), or severe postural deformities (2–4). Executive function was assessed using the Behavioral Assessment of the Dysexecutive Syndrome (BADS) and an age-controlled standardized BADS score <70 was defined as ED. Age-controlled standardized BADS scores were compared across the three groups using the Kruskal-Wallis test. Relationship between ED and the severity of postural deformities was assessed using the Mann-Whitney U test. Age-controlled standardized BADS score significantly differed among the three groups . ED was significantly related to the severity of postural deformities . The severity of postural deformities was associated with a lower age-controlled standardized BADS score and ED, and these findings suggest that postural deformities were associated with frontal dysfunction in patients with PD. Satoko Ninomiya, Akihiko Morita, Hiroko Teramoto, Takayoshi Akimoto, Hiroshi Shiota, and Satoshi Kamei Copyright © 2015 Satoko Ninomiya et al. All rights reserved. Cortex Fraxini (Qingpi) Protects Rat Pheochromocytoma Cells against 6-Hydroxydopamine-Induced Apoptosis Mon, 10 Aug 2015 14:06:52 +0000 Parkinson’s disease (PD) is a chronic neurodegenerative disorder having close relationship with oxidative stress induced by reactive oxygen species (ROS). Cortex Fraxini (QP) is a kind of traditional Chinese medicinal herb with antioxidant properties. It may be a potential candidate for preventing the development of chronic neurodegenerative diseases. Thus, the key objective of the current study was to investigate the neuroprotective effect of QP water extract on 6-hydroxydopamine (6-OHDA) induced apoptosis in rat pheochromocytoma (PC12) cells. It was found that QP water extract possesses strong antioxidant property with SC50 = 0.15 mg/mL. Total phenolic content of QP water extract was found to be 200.78 ± 2.65 mg GAE/g. QP water extract’s free radical scavenging capacity was demonstrated by reversing the increased level of intracellular ROS induced by 6-OHDA, using 2′,7′-dichlorodihydrofluorescein diacetate. Moreover, QP water extract (0.5 mg/mL) could remarkably increase the viability of PC12 cells treated with 6-OHDA. The protective effect of QP water extract was found to be via inhibiting MEK/ERK pathway and reversing PI3-K/Akt/GSK3β pathway. The current results suggest that QP might be a potential candidate for preventing the development of neurodegenerative diseases, such as PD. Jing-Jie Li, Shi-Ya Zhou, Huan Zhang, Kim-Hung Lam, Simon Ming-Yuen Lee, Peter Hoi-Fu Yu, and Shun-Wan Chan Copyright © 2015 Jing-Jie Li et al. All rights reserved. Plasma Prolidase Activity and Oxidative Stress in Patients with Parkinson’s Disease Sun, 09 Aug 2015 08:39:27 +0000 Prolidase deficiency has been related to mental retardation and oxidative stress. The study aimed to observe plasma prolidase activity (PPA), total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI) in patients with Parkinson’s disease (PD). 240 subjects with PD and 150 healthy volunteers were considered as cases and controls, respectively. PPA, TOS, TAS, and OSI were measured spectrophotometrically. PPA and TAS in cases were more significantly decreased than controls , while TOS and OSI were significantly increased . In cases, nonsignificant, positive correlation was observed between PPA and TOS and OSI while significant, negative correlation was observed between PPA and TAS . PPA in cases was nonsignificantly decreased with increased duration of PD while TAS was significantly decreased and TOS and OSI were significantly increased . It was observed that higher age groups had decreased PPA, and TAS and increased TOS and OSI compared to lower age groups in cases. In summary, patients with PD have decreased PPA and increased oxidative stress compared to healthy volunteers. PPA was associated with oxidative stress markers in patients with PD. Decreased PPA and TAS and increased TOS and OSI were associated with progression of disease and higher age. Akhilesh Kumar Verma, Janak Raj, Vivek Sharma, Tej Bali Singh, Shalabh Srivastava, and Ragini Srivastava Copyright © 2015 Akhilesh Kumar Verma et al. All rights reserved. Comparative Proteomic Analysis of Carbonylated Proteins from the Striatum and Cortex of Pesticide-Treated Mice Sun, 09 Aug 2015 07:06:47 +0000 Epidemiological studies indicate exposures to the herbicide paraquat (PQ) and fungicide maneb (MB) are associated with increased risk of Parkinson’s disease (PD). Oxidative stress appears to be a premier mechanism that underlies damage to the nigrostriatal dopamine system in PD and pesticide exposure. Enhanced oxidative stress leads to lipid peroxidation and production of reactive aldehydes; therefore, we conducted proteomic analyses to identify carbonylated proteins in the striatum and cortex of pesticide-treated mice in order to elucidate possible mechanisms of toxicity. Male C57BL/6J mice were treated biweekly for 6 weeks with saline, PQ (10 mg/kg), MB (30 mg/kg), or the combination of PQ and MB (PQMB). Treatments resulted in significant behavioral alterations in all treated mice and depleted striatal dopamine in PQMB mice. Distinct differences in 4-hydroxynonenal-modified proteins were observed in the striatum and cortex. Proteomic analyses identified carbonylated proteins and peptides from the cortex and striatum, and pathway analyses revealed significant enrichment in a variety of KEGG pathways. Further analysis showed enrichment in proteins of the actin cytoskeleton in treated samples, but not in saline controls. These data indicate that treatment-related effects on cytoskeletal proteins could alter proper synaptic function, thereby resulting in impaired neuronal function and even neurodegeneration. Christina Coughlan, Douglas I. Walker, Kelly M. Lohr, Jason R. Richardson, Laura M. Saba, W. Michael Caudle, Kristofer S. Fritz, and James R. Roede Copyright © 2015 Christina Coughlan et al. 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.