Parkinson’s Disease The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Articulatory Changes in Vowel Production following STN DBS and Levodopa Intake in Parkinson’s Disease Wed, 07 Oct 2015 13:42:50 +0000 Purpose. To investigate the impact of deep brain stimulation of the subthalamic nucleus (STN DBS) and levodopa intake on vowel articulation in dysarthric speakers with Parkinson’s disease (PD). Methods. Vowel articulation was assessed in seven Quebec French speakers diagnosed with idiopathic PD who underwent STN DBS. Assessments were conducted on- and off-medication, first prior to surgery and then 1 year later. All recordings were made on-stimulation. Vowel articulation was measured using acoustic vowel space and formant centralization ratio. Results. Compared to the period before surgery, vowel articulation was reduced after surgery when patients were off-medication, while it was better on-medication. The impact of levodopa intake on vowel articulation changed with STN DBS: before surgery, levodopa impaired articulation, while it no longer had a negative effect after surgery. Conclusions. These results indicate that while STN DBS could lead to a direct deterioration in articulation, it may indirectly improve it by reducing the levodopa dose required to manage motor symptoms. These findings suggest that, with respect to speech production, STN DBS and levodopa intake cannot be investigated separately because the two are intrinsically linked. Along with motor symptoms, speech production should be considered when optimizing therapeutic management of patients with PD. Vincent Martel Sauvageau, Johanna-Pascale Roy, Léo Cantin, Michel Prud’Homme, Mélanie Langlois, and Joël Macoir Copyright © 2015 Vincent Martel Sauvageau et al. All rights reserved. The Interaction between Obstructive Sleep Apnea and Parkinson’s Disease: Possible Mechanisms and Implications for Cognitive Function Mon, 05 Oct 2015 14:03:44 +0000 Parkinson’s disease (PD) is a relentlessly progressive neurodegenerative disorder associated with hallmark motor and nonmotor symptoms (NMS) such as sleep disturbances and cognitive dysfunction. While dopaminergic treatments have improved the motor aspects of PD, progression remains inevitable. Research has recently increasingly focused on strategies to modify disease progression and on nonmotor manifestations of PD, given their impact on patients’ quality of life. Obstructive sleep apnea (OSA) is a treatable sleep disorder, common in the general population, associated with excessive daytime sleepiness and neurocognitive deficits. Neuroimaging has demonstrated structural and functional changes in OSA patients; in animal models, OSA causes brain inflammation and oxidative injury, including in key areas involved in PD pathophysiology such as locus coeruleus. The prevalence of OSA in PD has been variable in studies to date, and potential consequences and interrelationship between the two disorders have not been well studied. There is however emerging evidence that OSA is associated with increased NMS in PD, particularly cognitive dysfunction. This review focuses on the possible interrelationship between OSA and PD. Mechanisms promoting OSA in PD will be reviewed, as well as mechanisms whereby OSA can affect the neurodegenerative process in PD. Marta Kaminska, Anne-Louise Lafontaine, and R. John Kimoff Copyright © 2015 Marta Kaminska et al. All rights reserved. Restless Legs Syndrome and Leg Motor Restlessness in Parkinson’s Disease Sun, 04 Oct 2015 12:57:03 +0000 Sleep disturbances are important nonmotor symptoms in Parkinson’s disease (PD) that are associated with a negative impact on quality of life. Restless legs syndrome (RLS), which is characterized by an urge to move the legs accompanied by abnormal leg sensations, can coexist with PD, although the pathophysiology of these disorders appears to be different. RLS and PD both respond favorably to dopaminergic treatment, and several investigators have reported a significant relationship between RLS and PD. Sensory symptoms, pain, motor restlessness, akathisia, and the wearing-off phenomenon observed in PD should be differentiated from RLS. RLS in PD may be confounded by chronic dopaminergic treatment; thus, more studies are needed to investigate RLS in drug-naïve patients with PD. Recently, leg motor restlessness (LMR), which is characterized by an urge to move the legs that does not fulfill the diagnostic criteria for RLS, has been reported to be observed more frequently in de novo patients with PD than in age-matched healthy controls, suggesting that LMR may be a part of sensorimotor symptoms intrinsic to PD. In this paper, we provide an overview of RLS, LMR, and PD and of the relationships among these disorders. Keisuke Suzuki, Masayuki Miyamoto, Tomoyuki Miyamoto, and Koichi Hirata Copyright © 2015 Keisuke Suzuki et al. All rights reserved. A Polysomnographic Study of Parkinson’s Disease Sleep Architecture Sun, 04 Oct 2015 11:32:57 +0000 Sleep disturbance is a common nonmotor phenomenon in Parkinson’s disease (PD) affecting patient’s quality of life. In this study, we examined the association between clinical characteristics with sleep disorders and sleep architecture patterns in a PD cohort. Patients underwent a standardized polysomnography study (PSG) in their “on medication” state. We observed that male gender and disease duration were independently associated with obstructive sleep apnea (OSA). Only lower levodopa equivalent dose (LED) was associated with periodic limb movement disorders (PLMD). REM sleep behavior disorder (RBD) was more common among older patients, with higher MDS-UPDRS III scores, and LED. None of the investigated variables were associated with the awakenings/arousals (A/A). Sleep efficiency was predicted by amantadine usage and age, while sleep stage 1 was predicted by dopamine agonists and Hoehn & Yahr severity. The use of MAO-B inhibitors and MDS-UPDRS part III were predictors of sleep stages 2 and 3. Age was the only predictor of REM sleep stage and gender for total sleep time. We conclude that sleep disorders and architecture are poorly predictable by clinical PD characteristics and other disease related factors must also be contributing to these sleep disturbances. Daniel Martinez-Ramirez, Sol De Jesus, Roger Walz, Amin Cervantes-Arriaga, Zhongxing Peng-Chen, Michael S. Okun, Vanessa Alatriste-Booth, and Mayela Rodríguez-Violante Copyright © 2015 Daniel Martinez-Ramirez et al. All rights reserved. Balance Dysfunction in Parkinson’s Disease: The Role of Posturography in Developing a Rehabilitation Program Sun, 04 Oct 2015 08:08:53 +0000 Balance dysfunction (BD) in Parkinson’s disease (PD) is a disabling symptom, difficult to treat and predisposing to falls. The dopaminergic drugs or deep brain stimulation does not always provide significant improvements of BD and rehabilitative approaches have also failed to restore this condition. In this study, we investigated the suitability of quantitative posturographic indicators to early identify patients that could develop disabling BD. Parkinsonian patients not complaining of a subjective BD and controls were tested using a posturographic platform (PP) with open eyes (OE) and performing a simple cognitive task [counting (OEC)]. We found that patients show higher values of total standard deviation (SD) of body sway and along the medio-lateral (ML) axis during OE condition. Furthermore, total and ML SD of body sway during OE condition and total SD of body sway with OEC were higher than controls also in a subgroup of patients with normal Berg Balance Scale. We conclude that BD in Parkinsonian patients can be discovered before its appearance using a PP and that these data may allow developing specific rehabilitative treatment to prevent or delay their onset. Davide Ferrazzoli, Alfonso Fasano, Roberto Maestri, Rossana Bera, Grazia Palamara, Maria Felice Ghilardi, Gianni Pezzoli, and Giuseppe Frazzitta Copyright © 2015 Davide Ferrazzoli et al. All rights reserved. The Parkinsonian Gait Spatiotemporal Parameters Quantified by a Single Inertial Sensor before and after Automated Mechanical Peripheral Stimulation Treatment Thu, 01 Oct 2015 12:15:01 +0000 This study aims to evaluate the change in gait spatiotemporal parameters in subjects with Parkinson’s disease (PD) before and after Automated Mechanical Peripheral Stimulation (AMPS) treatment. Thirty-five subjects with PD and 35 healthy age-matched subjects took part in this study. A dedicated medical device (Gondola) was used to administer the AMPS. All patients with PD were treated in off levodopa phase and their gait performances were evaluated by an inertial measurement system before and after the intervention. The one-way ANOVA for repeated measures was performed to assess the differences between pre- and post-AMPS and the one-way ANOVA to assess the differences between PD patients and the control group. Spearman’s correlations assessed the associations between patients with PD clinical status (H&Y) and the percentage of improvement of the gait variables after AMPS ( for all tests). The PD group had an improvement of 14.85% in the stride length; 14.77% in the gait velocity; and 29.91% in the gait propulsion. The correlation results showed that the higher the H&Y classification, the higher the stride length percentage of improvement. The treatment based on AMPS intervention seems to induce a better performance in the gait pattern of PD patients, mainly in intermediate and advanced stages of the condition. Ana Kleiner, Manuela Galli, Maria Gaglione, Daniela Hildebrand, Patrizio Sale, Giorgio Albertini, Fabrizio Stocchi, and Maria Francesca De Pandis Copyright © 2015 Ana Kleiner et al. All rights reserved. Living with Parkinson’s and the Emerging Role of Occupational Therapy Thu, 01 Oct 2015 08:49:47 +0000 Parkinson’s disease is a chronic and increasingly complex condition, demanding multidisciplinary management. Over the last twenty years or so, alongside the growth of specialist services and healthcare teams specifically developed for people with Parkinson’s, occupational therapy has grown in recognition as a treatment option, especially since evidence of its efficacy is now slowly emerging. The purpose of this work is to outline the role of occupational therapy clinical practice in the management of people living with Parkinson’s disease and its emergent evidence base, combined with details of current occupational therapy philosophy and process, as applicable to occupational therapy practice for people with Parkinson’s. The Canadian Practice Process Framework is used to structure this overview and was selected because it is a well-recognized, evidence-based tool used by occupational therapists and encompasses the core concepts of human occupation and person-centred practice. The framework employed allows the flexibility to reflect the pragmatic occupational therapy intervention process and so enables the illustration of the individually tailored approach required to accommodate to the complex pathology and personal, domestic, and social impacts, affecting the functioning of Parkinson’s disease patients on a daily basis. Jelka Jansa and Ana Aragon Copyright © 2015 Jelka Jansa and Ana Aragon. All rights reserved. Action Observation and Motor Imagery: Innovative Cognitive Tools in the Rehabilitation of Parkinson’s Disease Thu, 01 Oct 2015 07:02:54 +0000 Parkinson’s disease (PD) is characterized by a progressive impairment of motor skills with deterioration of autonomy in daily living activities. Physiotherapy is regarded as an adjuvant to pharmacological and neurosurgical treatment and may provide small and short-lasting clinical benefits in PD patients. However, the development of innovative rehabilitation approaches with greater long-term efficacy is a major unmet need. Motor imagery (MI) and action observation (AO) have been recently proposed as a promising rehabilitation tool. MI is the ability to imagine a movement without actual performance (or muscle activation). The same cortical-subcortical network active during motor execution is engaged in MI. The physiological basis of AO is represented by the activation of the “mirror neuron system.” Both MI and AO are involved in motor learning and can induce improvements of motor performance, possibly mediated by the development of plastic changes in the motor cortex. The review of available evidences indicated that MI ability and AO feasibility are substantially preserved in PD subjects. A few preliminary studies suggested the possibility of using MI and AO as parts of rehabilitation protocols for PD patients. Giovanni Abbruzzese, Laura Avanzino, Roberta Marchese, and Elisa Pelosin Copyright © 2015 Giovanni Abbruzzese et al. All rights reserved. Pentoxifylline Neuroprotective Effects Are Possibly Related to Its Anti-Inflammatory and TNF-Alpha Inhibitory Properties, in the 6-OHDA Model of Parkinson’s Disease Tue, 29 Sep 2015 11:15:33 +0000 Pentoxifylline (PTX) is a phosphodiesterase inhibitor with anti-TNF-alpha activity, associated with its anti-inflammatory action. Considering Parkinson’s disease (PD) as a neuroinflammatory disorder, the objectives were to evaluate PTX neuroprotective properties, in a model of PD. Male Wistar rats, divided into sham-operated (SO), untreated 6-OHDA, and 6-OHDA treated with PTX (10, 25, and 50 mg/kg) groups, received a unilateral 6-OHDA injection, except the SO group administered with saline. Treatments started 24 h after surgery and continued for 15 days when the animals were submitted to apomorphine-induced rotations, open field, and forced swimming tests. At the next day, they were euthanized and their striata processed for neurochemical (DA and DOPAC determinations), histological, and immunohistochemical (Fluoro-Jade, TH, DAT, OX-42, TNF-alpha, COX-2, and iNOS) studies. PTX reversed the behavioral changes observed in the untreated 6-OHDA animals. Furthermore, PTX partially reversed the decrease in DA contents and improved neuronal viability. In addition, decreases in immunostaining for TH and dopamine transporter (DAT) were reversed. The untreated 6-OHDA group showed intense OX-42, TNF-alpha, COX-2, and iNOS immunoreactivities, which were attenuated by PTX. In conclusion, we demonstrated a neuroprotective effect of PTX, possibly related to its anti-inflammatory and antioxidant actions, indicating its potential as an adjunct treatment for PD. Kelly Rose Tavares Neves, Hélio Vitoriano Nobre Jr., Luzia Kalyne A. M. Leal, Geanne Matos de Andrade, Gerly Anne de Castro Brito, and Glauce Socorro de Barros Viana Copyright © 2015 Kelly Rose Tavares Neves et al. All rights reserved. Potential Biomarkers of the Earliest Clinical Stages of Parkinson’s Disease Mon, 21 Sep 2015 09:03:43 +0000 Parkinson’s disease (PD) is a widespread neurodegenerative disorder. Despite the intensive studies of this pathology, in general, the picture of the etiopathogenesis has still not been clarified fully. To understand better the mechanisms underlying the pathogenesis of PD, we analyzed the expression of 10 genes in the peripheral blood of treated and untreated patients with PD. 35 untreated patients with PD and 12 treated patients with Parkinson’s disease (Hoehn and Yahr scores 1-2) were studied. An analysis of the mRNA levels of ATP13A2, PARK2, PARK7, PINK1, LRRK2, SNCA, ALDH1A1, PDHB, PPARGC1A, and ZNF746 genes in the peripheral blood of patients was carried out using reverse transcription followed by real-time PCR. A statistically significant and specific increase by more than 1.5-fold in the expression of the ATP13A2, PARK7, and ZNF746 genes was observed in patients with PD. Based on these results, it can be suggested that the upregulation of the mRNA levels of ATP13A2, PARK7, and ZNF746 in untreated patients in the earliest clinical stages can also be observed in the preclinical stages of PD, and that these genes can be considered as potential biomarkers of the preclinical stage of PD. Anelya Kh. Alieva, Elena V. Filatova, Aleksey V. Karabanov, Sergey N. Illarioshkin, Petr A. Slominsky, and Maria I. Shadrina Copyright © 2015 Anelya Kh. Alieva et al. All rights reserved. Effect of GBA Mutations on Phenotype of Parkinson’s Disease: A Study on Chinese Population and a Meta-Analysis Wed, 02 Sep 2015 08:52:16 +0000 GBA has been identified as a genetic risk factor for PD. Whether the clinical manifestations of PD patients with or without GBA mutations are different has still not reached a consensus. We firstly detected the GBA mutation L444P in 1147 Chinese PD patients and simultaneously evaluated their corresponding clinical data. Then we compared the phenotypes between 646 PD patients with GBA mutations and 10344 PD patients without GBA mutations worldwide through meta-analysis. Through the method of meta-analysis, there was significant difference in age at onset (MD = −3.10 [95% CI: −4.88, −1.32]), bradykinesia as an initial symptom (OR = 1.49 [95% CI: 1.15, 1.94]), having family history (OR = 1.50 [95% CI: 1.18, 1.91]), and dementia (OR = 3.21 [95% CI: 1.97, 5.24]) during the comparison between PD patients with and without GBA mutations. While, in the aspect of tremor as an initial symptom (OR = 0.81 [95% CI: 0.64, 1.03]), the severity of motor symptoms such as H-Y (MD = 0.06 [95% CI: −0.06, 0.17]) and UPDRS-III (MD = 1.61 [95% CI: −0.65, 3.87]) and having dyskinesia (OR = 1.60 [95% CI: 0.90, 2.84]) during the comparison between the two groups revealed no statistical differences. Our results suggested that the phenotypes of PD patients with GBA mutations are different from GBA noncarriers. Yuan Zhang, Qi-ying Sun, Yu-wen Zhao, Li Shu, Ji-feng Guo, Qian Xu, Xin-xiang Yan, and Bei-sha Tang Copyright © 2015 Yuan Zhang et al. All rights reserved. MRI Guided Focused Ultrasound Thalamotomy for Moderate-to-Severe Tremor in Parkinson’s Disease Wed, 02 Sep 2015 07:26:42 +0000 Background. Thalamotomy is effective in alleviating tremor in Parkinson’s disease (PD). Methods. Seven PD patients, mean age 59.4 ± 9.8 years (range, 46–74) with a mean disease duration of 5.4 ± 2.8 years (range, 2–10) suffering from severe refractory tremor, underwent ventral intermediate nucleus thalamotomy using MRI guided focused ultrasound (MRgFUS), an innovative technology that enables noninvasive surgery. Results. Tremor stopped in the contralateral upper extremity in all patients immediately following treatment. Total UPDRS decreased from 37.4 ± 12.2 to 18.8 ± 11.1 and PDQ-39 decreased from 42.3 ± 16.4 to 21.6 ± 10.8 following MRgFUS. These effects were sustained (mean follow-up 7.3 months). Adverse events during MRgFUS included headache , dizziness , vertigo , and lip paresthesia and following MRgFUS were hypogeusia , unsteady feeling when walking (, resolved), and disturbance when walking tandem (, resolved). Conclusions. Thalamotomy using MRgFUS is safe and effective in PD patients. Large randomized studies are needed to assess prolonged efficacy and safety. Ilana Schlesinger, Ayelet Eran, Alon Sinai, Ilana Erikh, Maria Nassar, Dorith Goldsher, and Menashe Zaaroor Copyright © 2015 Ilana Schlesinger et al. 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.