Parkinson’s Disease The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Targeting Histone Deacetylases: A Novel Approach in Parkinson’s Disease Wed, 28 Jan 2015 14:14:50 +0000 The worldwide prevalence of movement disorders is increasing day by day. Parkinson’s disease (PD) is the most common movement disorder. In general, the clinical manifestations of PD result from dysfunction of the basal ganglia. Although the exact underlying mechanisms leading to neural cell death in this disease remains unknown, the genetic causes are often established. Indeed, it is becoming increasingly evident that chromatin acetylation status can be impaired during the neurological disease conditions. The acetylation and deacetylation of histone proteins are carried out by opposing actions of histone acetyltransferases (HATs) and histone deacetylases (HDACs), respectively. In the recent past, studies with HDAC inhibitors result in beneficial effects in both in vivo and in vitro models of PD. Various clinical trials have also been initiated to investigate the possible therapeutic potential of HDAC inhibitors in patients suffering from PD. The possible mechanisms assigned for these neuroprotective actions of HDAC inhibitors involve transcriptional activation of neuronal survival genes and maintenance of histone acetylation homeostasis, both of which have been shown to be dysregulated in PD. In this review, the authors have discussed the putative role of HDAC inhibitors in PD and associated abnormalities and suggest new directions for future research in PD. Sorabh Sharma and Rajeev Taliyan Copyright © 2015 Sorabh Sharma and Rajeev Taliyan. All rights reserved. Levetiracetam Ameliorates L-DOPA-Induced Dyskinesia in Hemiparkinsonian Rats Inducing Critical Molecular Changes in the Striatum Tue, 27 Jan 2015 14:24:47 +0000 L-DOPA-induced dyskinesias (LID) remain a major problem of long-term therapy of Parkinson’s disease. Levetiracetam, a new antiepileptic drug, has been shown to reduce LID, but the mechanisms underlying its effects are unknown. In this study, we assessed the effect of levetiracetam on key mediators of LID in rats with 6-hydroxydopamine (6-OHDA) lesions. Following chronic administration of L-DOPA (12 mg/kg, twice daily for 14 days), rats developed abnormal involuntary movements (AIMs), but co-administration of levetiracetam (15, 30, and 60 mg/kg) with equivalent L-DOPA dosing significantly reduced AIMs scores in a dose dependent manner. The effects of levetiracetam were associated with changes in striatal expression of FosB, phosphorylated extracellular signal-regulated kinases 1 and 2 (p-ERK1/2), and phosphorylated cAMP-regulated phosphoprotein of 32 kDa (p-DARPP-32). These data support that levetiracetam acts at multiple sites in the pathogenetic cascade of LID, and that further understanding of these actions of antiepileptics may contribute to developing new LID therapies. Huan Du, Shuke Nie, Guiqin Chen, Kai Ma, Yan Xu, Zhentao Zhang, Stella M. Papa, and Xuebing Cao Copyright © 2015 Huan Du et al. All rights reserved. Identification of Changing Lower Limb Neuromuscular Activation in Parkinson’s Disease during Treadmill Gait with and without Levodopa Using a Nonlinear Analysis Index Mon, 19 Jan 2015 13:11:58 +0000 Analysis of electromyographic (EMG) data is a cornerstone of research related to motor control in Parkinson’s disease. Nonlinear EMG analysis tools have shown to be valuable, but analysis is often complex and interpretation of the data may be difficult. A previously introduced algorithm (SYNERGOS) that provides a single index value based on simultaneous multiple muscle activations (MMA) has been shown to be effective in detecting changes in EMG activation due to modifications of walking speeds in healthy adults. In this study, we investigated if SYNERGOS detects MMA changes associated with both different walking speeds and levodopa intake. Nine male Parkinsonian patients walked on a treadmill with increasing speed while on or off medication. We collected EMG data and computed SYNERGOS indices and employed a restricted maximum likelihood linear mixed model to the values. SYNERGOS was sensitive to neuromuscular modifications due to both alterations of gait speed and intake of levodopa. We believe that the current experiment provides evidence for the potential value of SYNERGOS as a nonlinear tool in clinical settings, by providing a single value index of MMA. This could help clinicians to evaluate the efficacy of interventions and treatments in Parkinson’s disease in a simple manner. Amir Pourmoghaddam, Marius Dettmer, Daniel P. O’Connor, William H. Paloski, and Charles S. Layne Copyright © 2015 Amir Pourmoghaddam et al. All rights reserved. Disorders of the Oral Cavity in Parkinson’s Disease and Parkinsonian Syndromes Thu, 15 Jan 2015 11:56:14 +0000 Awareness of nonmotor symptoms of Parkinson’s disease is growing during the last decade. Among these, oral cavity disorders are, although prevalent, often neglected by the patients, their caregivers, and physicians. Some of these disorders include increased prevalence of caries and periodontal disease, sialorrhea and drooling, xerostomia, orofacial pain, bruxism, and taste impairment. Though many of these disorders are not fully understood yet and relatively few controlled trials have been published regarding their treatment, physicians should be aware of the body of evidence that does exist on these topics. This paper reviews current knowledge regarding the epidemiology, pathophysiology, and treatment options of disorders of the oral cavity in Parkinson’s disease patients. Yair Zlotnik, Yacov Balash, Amos D. Korczyn, Nir Giladi, and Tanya Gurevich Copyright © 2015 Yair Zlotnik et al. All rights reserved. MRI Correlates of Parkinson’s Disease Progression: A Voxel Based Morphometry Study Tue, 06 Jan 2015 07:02:12 +0000 We investigated structural brain differences between a group of early-mild PD patients at different phases of the disease and healthy subjects using voxel-based morphometry (VBM). 20 mild PD patients compared to 15 healthy at baseline and after 2 years of follow-up. VBM is a fully automated technique, which allows the identification of regional differences in the gray matter enabling an objective analysis of the whole brain between groups of subjects. With respect to controls, PD patients exhibited decreased GM volumes in right putamen and right parietal cortex. After 2 years of disease, the same patients confirmed GM loss in the putamen and parietal cortex; a significant difference was also observed in the area of pedunculopontine nucleus (PPN) and in the mesencephalic locomotor region (MLR). PD is associated with brain morphological changes in cortical and subcortical structures. The first regions to be affected in PD seem to be the parietal cortex and the putamen. A third structure that undergoes atrophy is the part of the inferior-posterior midbrain, attributable to the PPN and MLR. Our findings provide new insight into the brain involvement in PD and could contribute to a better understanding of the sequence of events occurring in these patients. Valentina Fioravanti, Francesca Benuzzi, Luca Codeluppi, Sara Contardi, Francesco Cavallieri, Paolo Nichelli, and Franco Valzania Copyright © 2015 Valentina Fioravanti et al. All rights reserved. Altered Brain Activation in Early Drug-Naive Parkinson’s Disease during Heat Pain Stimuli: An fMRI Study Mon, 05 Jan 2015 14:20:13 +0000 Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by motor and nonmotor signs and symptoms. To date, many studies of PD have focused on its cardinal motor symptoms. To study the nonmotor signs of early PD, we investigated the reactions solicited by heat pain stimuli in early untreated PD patients without pain using fMRI. The activation patterns of contact heat stimuli (51°C) were assessed in 14 patients and 17 age- and sex-matched healthy controls. Patients with PD showed significant decreases in activation of the superior temporal gyrus (STG) and insula compared with controls. In addition, a significant relationship between activation of the insula and STG and the pain scores was observed in healthy controls but not in PD. This study provided further support that the insula and STG are important parts of the somatosensory circuitry recruited during the period of pain. The hypoactivity of the STG and insula in PD implied that functions including affective, cognitive, and sensory-discriminative processes, which are associated with the insula and STG, were disturbed. This finding supports the view that leaving early PD untreated could be tied directly to central nervous system dysfunction. Ying Tan, Juan Tan, Cheng Luo, Wenjuan Cui, Hui He, Yi Bin, Jiayan Deng, Rui Tan, Wenrong Tan, Tao Liu, Nanlin Zeng, Ruhui Xiao, Dezhong Yao, and Xiaoming Wang Copyright © 2015 Ying Tan et al. All rights reserved. Comparison of the Psychological Symptoms and Disease-Specific Quality of Life between Early- and Typical-Onset Parkinson’s Disease Patients Mon, 29 Dec 2014 09:57:50 +0000 The impact of Parkinson’s disease (PD) on psychological status and quality of life (QoL) may vary depending on age of disease onset. The aim of this study was to compare psychological symptoms and disease-specific QoL between early onset versus the rest of the PD patients. A total number of 140 PD patients with the mean current age of 61.3  yr were recruited in this study. PD patients with the onset age of ≤50 yr were defined as “early-onset” (EOPD) group , while the ones with >50 yr at the time of diagnosis were categorized as the “typical-onset” (TOPD) patients . Different questionnaires and scales were used for between-group comparisons including PDQ39, HADS (hospital anxiety and depression scale), FSS (fatigue severity scale), MNA (mininutritional assessment), and the UPDRS. Depression score was significantly higher in EOPD group (6.3 versus 4.5 , ). Among different domains of QoL, emotion score was also significantly higher in the EOPD group (32.3 versus 24.4 , ). Our findings showed more severe depression and more impaired emotional domain of QoL in early-onset PD patients. Depression and anxiety play an important role to worsen QoL among both EOPD and TOPD patients, while no interaction was observed in the efficacy of these two psychiatric symptoms and the onset age of PD patients. Seyed-Mohammad Fereshtehnejad, Hasti Hadizadeh, Farzaneh Farhadi, Gholam Ali Shahidi, Ahmad Delbari, and Johan Lökk Copyright © 2014 Seyed-Mohammad Fereshtehnejad et al. All rights reserved. Polysomnographic Features of Sleep Disturbances and REM Sleep Behavior Disorder in the Unilateral 6-OHDA Lesioned Hemiparkinsonian Rat Thu, 25 Dec 2014 06:14:42 +0000 Sleep pattern disruption, specifically REM sleep behavior disorder (RBD), is a major nonmotor cause of disability in PD. Understanding the pathophysiology of these sleep pattern disturbances is critical to find effective treatments. 24-hour polysomnography (PSG), the gold standard for sleep studies, has never been used to test sleep dysfunction in the standard 6-OHDA lesioned hemiparkinsonian (HP) rat PD model. In this study, we recorded 24-hour PSG from normal and HP rats. Recordings were scored into wake, rapid eye movement (REM), and non-REM (NREM). We then examined EEG to identify REM periods and EMG to check muscle activity during REM. Normal rats showed higher wakefulness (70–80%) during the dark phase and lower wakefulness (20%) during the light phase. HP rats showed 30–50% sleep in both phases, less modulation and synchronization to the light schedule , and more long run lengths of wakefulness . HP rats also had more REM epochs with muscle activity than control rats . Our findings that the sleep architecture in the HP rat resembles that of PD patients demonstrate the value of this model in studying the pathophysiological basis of PD sleep disturbances and preclinical therapeutics for PD related sleep disorders including RBD. Quynh Vo, Timothy P. Gilmour, Kala Venkiteswaran, Jidong Fang, and Thyagarajan Subramanian Copyright © 2014 Quynh Vo et al. All rights reserved. Measuring Hemoglobin Levels in the Optic Disc of Parkinson’s Disease Patients Using New Colorimetric Analysis Software Tue, 23 Dec 2014 06:31:50 +0000 Objective. To evaluate a new method of measuring hemoglobin (Hb) levels and quantifying the color changes in the optic nerve head of Parkinson’s disease (PD) patients. We also compared differences in retinal nerve fiber layer (RNFL) thicknesses obtained using spectral domain optical coherence tomography (OCT) device between PD group and healthy group. Methods. One hundred and fifty-five PD patients and 91 sex- and age-matched healthy subjects were included in this cross-sectional study. OCT examinations and one photograph of the optic disc were performed. The Laguna ONhE (“optic nerve hemoglobin”; Insoft SL, Tenerife, Spain) software was used to analyze the Hb level on the acquired optic disc photographs. Results. PD patients exhibited significantly reduced mean optic disc Hb percentages (57.56% in PD, 67.63% in healthy subjects; ) as well as reduced Hb in almost all analyzed sectors, with the largest differences detected in the inferior and nasal sectors. RNFL parameters were significantly reduced in PD patients compared with healthy subjects, especially in the inferior quadrant. Conclusions. Measurements of optic disc Hb levels obtained with the Laguna ONhE software had good ability to detect optic nerve color changes (more papillary paleness and consequently this could suggest optic atrophy and axonal loss) in PD patients. Maria Pilar Bambo, Elena Garcia-Martin, Maria Satue, Susana Perez-Olivan, Silvia Alayon, Marta Gonzalez-Hernandez, Vicente Polo, Jose Manuel Larrosa, and Manuel Gonzalez-De la Rosa Copyright © 2014 Maria Pilar Bambo et al. All rights reserved. Effect of Centella asiatica Leaf Extract on the Dietary Supplementation in Transgenic Drosophila Model of Parkinson’s Disease Thu, 27 Nov 2014 00:10:08 +0000 The role of Centella asiatica L. leaf extract was studied on the transgenic Drosophila model flies expressing normal human alpha synuclein (h-αS) in the neurons. The leaf extract was prepared in acetone and was subjected to GC-MS analysis. C. asiatica extract at final concentration of 0.25, 0.50, and 1.0 μL/mL was mixed with the diet and the flies were allowed feeding on it for 24 days. The effect of extract was studied on the climbing ability, activity pattern, lipid peroxidation, protein carbonyl content, glutathione content, and glutathione-S-transferase activity in the brains of transgenic Drosophila. The exposure of extract to PD model flies results in a significant delay in the loss of climbing ability and activity pattern and reduced the oxidative stress () in the brains of PD flies as compared to untreated PD flies. The results suggest that C. asiatica leaf extract is potent in reducing the PD symptoms in transgenic Drosophila model of Parkinson’s disease. Yasir Hasan Siddique, Falaq Naz, Smita Jyoti, Ambreen Fatima, Saba Khanam, Rahul, Fahad Ali, Syed Faiz Mujtaba, and Mohammad Faisal Copyright © 2014 Yasir Hasan Siddique et al. All rights reserved. Recurrent Falls in People with Parkinson’s Disease without Cognitive Impairment: Focusing on Modifiable Risk Factors Sun, 23 Nov 2014 08:03:21 +0000 Falls can be considered a disabling feature in Parkinson’s disease. We aimed to identify risk factors for falling, testing simultaneously the ability of disease-specific and balance-related measures. We evaluated 171 patients, collecting demographic and clinical data, including standardized assessments with the Unified Parkinson’s Disease Rating Scale (UPDRS), activities of daily living (ADL) and motor sections, modified Hoehn and Yahr Scale, Schwab and England, eight-item Parkinson’s Disease Questionnaire, Activities-specific Balance Confidence Scale, Falls Efficacy Scale-International (FES-I), Berg Balance Scale, Dynamic Gait Index, Functional Reach, and Timed Up and Go. ROC curves were constructed to determine the cutoff scores for all measures. Variables with entered a logistic regression model. The prevalence of recurrent falls was 30% (95% CI 24%–38%). In multivariate analysis, independent risk factors for recurrent falls were () levodopa equivalent dose (OR = 1.283 per 100 mg increase; 95% CI = 1.092–1.507), UPDRS-ADL > 16 points (OR = 10.0; 95% CI = 3.6–28.3), FES-I > 30 points (OR = 6.0; 95% CI = 1.6–22.6), and Berg ≤ 48 points (OR = 3.9; 95% CI = 1.2–12.7).We encourage the utilization of these modifiable risk factors in the screening of fall risk. Lorena R. S. Almeida, Guilherme T. Valença, Nádja N. Negreiros, Elen B. Pinto, and Jamary Oliveira-Filho Copyright © 2014 Lorena R. S. Almeida et al. All rights reserved. Parkinson’s Disease: Low-Dose Haloperidol Increases Dopamine Receptor Sensitivity and Clinical Response Thu, 20 Nov 2014 07:01:36 +0000 Background. It is known that ultra-low doses of haloperidol can cause dopamine supersensitivity of dopamine D2 receptors and related behaviour in animals. Objective. The objective was to determine whether a daily ultra-low dose of 40 micrograms of haloperidol could enhance the clinical action of levodopa in Parkinson’s disease patients. Method. While continuing their daily treatment with levodopa, 16 patients with Parkinson’s disease were followed weekly for six weeks. They received an add-on daily dose of 40 micrograms of haloperidol for the first two weeks only. The SPES/SCOPA scale (short scale for assessment of motor impairments and disabilities in Parkinson’s disease) was administered before treatment and weekly throughout the trial. Results. The results showed a mean decrease in SPES/SCOPA scores after one week of the add-on treatment. Conclusion. SCOPA scores decreased after the addition of low-dose haloperidol to the standard daily levodopa dose. This finding is consistent with an increase in sensitivity of dopamine D2 receptors induced by haloperidol. Such treatment for Parkinson’s disease may possibly permit the levodopa dose to be reduced and, thus, delay the onset of levodopa side effects. Craig J. Hudson, Philip Seeman, and Mary V. Seeman Copyright © 2014 Craig J. Hudson et al. All rights reserved. Is the MDS-UPDRS a Good Screening Tool for Detecting Sleep Problems and Daytime Sleepiness in Parkinson’s Disease? Mon, 17 Nov 2014 07:47:27 +0000 Movement Disorder Society-sponsored Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) has separate items for measuring sleep problems (item 1.7) and daytime sleepiness (1.8). The aim of our study was to evaluate the screening sensitivity and specificity of these items to the PD Sleep Scale 2nd version (PDSS-2) and Epworth Sleepiness Scale (ESS). In this nationwide, cross-sectional study 460 PD patients were enrolled. Spearman’s rank correlation coefficients were calculated between the individual items, domains, and the total score of PDSS-2 and item 1.7 of MDS-UPDRS. Similarly, the items and the total score of ESS were contrasted to item 1.8 of MDS-UPDRS. After developing generalized ordinal logistic regression models, the transformed and observed scores were compared by Lin’s Concordance Correlation Coefficient. Only item 3 difficulties staying asleep and the “disturbed sleep” domain of PDSS-2 showed high correlation with “sleep problems” item 1.7 of the MDS-UPDRS. Total score of PDSS-2 had moderate correlation with this MDS-UPRDS item. The total score of ESS showed the strongest, but still moderate, correlation with “daytime sleepiness” item 1.8 of MDS-UPDRS. As intended, the MDS-UPDRS serves as an effective screening tool for both sleep problems and daytime sleepiness and identifies subjects whose disabilities need further investigation. Krisztina Horváth, Zsuzsanna Aschermann, Péter Ács, Edit Bosnyák, Gabriella Deli, Endre Pál, József Janszky, Béla Faludi, Ildikó Késmárki, Sámuel Komoly, Magdolna Bokor, Eszter Rigó, Júlia Lajtos, Péter Klivényi, György Dibó, László Vécsei, Annamária Takáts, Adrián Tóth, Piroska Imre, Ferenc Nagy, Mihály Herceg, Anita Kamondi, Eszter Hidasi, and Norbert Kovács Copyright © 2014 Krisztina Horváth et al. All rights reserved. Oleanolic Acid Enhances the Beneficial Effects of Preconditioning on PC12 Cells Thu, 13 Nov 2014 07:10:28 +0000 Preconditioning triggers endogenous protection against subsequent exposure to higher concentrations of a neurotoxin. In this study, we investigated whether exposure to oleanolic acid (OA) enhances the protective effects of preconditioning on PC12 cells exposed to 6-hydroxydopamine (6-OHDA). A concentration response curve was constructed using 6-OHDA (50, 150, 300, and 600 μM). The experiment consisted of 6 groups: untreated, OA only, Group 1: cells treated with 6-OHDA (50 μM) for 1 hour, Group 2: cells treated with 6-OHDA (150 μM) for 1 hour, Group 3: cells treated with 6-OHDA (50 μM) for 30 minutes followed 6 hours later by treatment with 6-OHDA (150 μM) for 30 minutes, and Group 4: cells treated as in group 3 but also received OA immediately after the second 6-OHDA treatment. Cell viability and apoptotic ratio were assessed using the MTT and Annexin V staining tests, respectively. In preconditioned cells, we found that cell viability remained high following exposure to 6-OHDA (150 μM). OA treatment enhanced the protective effects of preconditioning. Similarly, with the annexin V apoptosis test, preconditioning protected the cell and this was enhanced by OA. Therefore, preexposure of PC12 cells to low 6-OHDA concentration can protect against subsequent toxic insults of 6-OHDA and OA enhances this protection. Babongile C. Ndlovu, Willie M. U. Daniels, and Musa V. Mabandla Copyright © 2014 Babongile C. Ndlovu et al. All rights reserved. Validation of the Persian Translation of the Swallowing Disturbance Questionnaire in Parkinson’s Disease Patients Mon, 27 Oct 2014 08:45:05 +0000 Dysphagia, as a common finding in Parkinson’s disease (PD) patients, was estimated to be present in 80–95% of this population during different stages of the disease. The Swallowing Disturbance Questionnaire (SDQ) was created as a self-rated dysphagia screening tool in PD. According to the guidelines for cross-cultural adaptation, Persian version of this questionnaire (SDQ-P) was developed. 59 Persian patients (39 men and 20 women) participated in the study. They responded to the SDQ-P and underwent videofluoroscopic swallowing study (VFSS). Aspiration during VFSS was compared with questionnaire results for each individual. Cronbach’s alpha coefficient for the questionnaire was 0.86 and based on SDQ-P 15 patients (25.4%) were dysphagic, while 10 patients (16.9%) showed aspiration during VFSS. SDQ-P sensitivity and specificity in predicting aspiration were 96.7 and 91.2%; therefore, the SDQ-P could be a prognostic tool for aspiration. The positive predictive value (PPV), the negative predictive value (NPV), and the pre- and posttest probabilities of aspiration were 0.67, 1, 16.9%, and 66.7%, respectively. In summary, this study demonstrated the reliability and also the feasibility of SDQ-P for screening of aspiration in Iranian patients with PD. Further evaluation of SDQ-P in larger subject population would be suggested. Ali Rajaei, S. Abolfazl Azargoon, Mohammad Hussein Nilforoush, Ebrahim Barzegar Bafrooei, Fereshteh Ashtari, and Ahmad Chitsaz Copyright © 2014 Ali Rajaei et al. All rights reserved. Independent Validation of the SEND-PD and Correlation with the MDS-UPDRS Part IA Thu, 23 Oct 2014 06:32:03 +0000 Introduction. Neuropsychiatric symptoms in Parkinson’s disease can be assessed by the MDS-UPDRS part IA. The Scale for Evaluation of Neuropsychiatric Disorders in Parkinson’s disease (SEND-PD) has been recently developed to assess the severity of some neuropsychiatric symptoms. The objective of this study is to compare the performance of the SEND-PD with the corresponding items of the MDS-UPDRS part IA. Methods. Patients with Parkinson’s disease were evaluated using the MDS-UPDRS and the SEND-PD by independent raters. Partial SEND-PD and neuropsychiatric MDS-UPDRS part IA were constructed with equivalent items for comparison. Results. A total of 260 consecutive patients were included. Overall, 61.2% of the patients did not report any psychotic symptom and 83.5% did not report any ICD symptom. On the other hand, 78.5% of the patients did report at least one symptom related to apathy, depression, or anxiety. The partial SEND-PD score was (range from 0 to 16). The neuropsychiatric MDS-UPDRS part IA score was (range from 0 to 14). The correlation coefficient between corresponding items ranged from 0.67 to 0.98 and between both summary indexes was (all, ). Conclusion. A high association between equivalent items of the SEND-PD and the MDS-UPDRS was found. Mayela Rodríguez-Violante, Amin Cervantes-Arriaga, Salvador Velázquez-Osuna, Rodrigo Llorens-Arenas, Humberto Calderón-Fajardo, Dan Piña-Fuentes, and Pablo Martinez-Martin Copyright © 2014 Mayela Rodríguez-Violante et al. All rights reserved. Changes in Vowel Articulation with Subthalamic Nucleus Deep Brain Stimulation in Dysarthric Speakers with Parkinson’s Disease Tue, 21 Oct 2014 11:17:58 +0000 Purpose. To investigate changes in vowel articulation with the electrical deep brain stimulation (DBS) of the subthalamic nucleus (STN) in dysarthric speakers with Parkinson’s disease (PD). Methods. Eight Quebec-French speakers diagnosed with idiopathic PD who had undergone STN DBS were evaluated ON-stimulation and OFF-stimulation (1 hour after DBS was turned off). Vowel articulation was compared ON-simulation versus OFF-stimulation using acoustic vowel space and formant centralization ratio, calculated with the first () and second formant () of the vowels /i/, /u/, and /a/. The impact of the preceding consonant context on articulation, which represents a measure of coarticulation, was also analyzed as a function of the stimulation state. Results. Maximum vowel articulation increased during ON-stimulation. Analyses also indicate that vowel articulation was modulated by the consonant context but this relationship did not change with STN DBS. Conclusions. Results suggest that STN DBS may improve articulation in dysarthric speakers with PD, in terms of range of movement. Optimization of the electrical parameters for each patient is important and may lead to improvement in speech fine motor control. However, the impact on overall speech intelligibility may still be small. Clinical considerations are discussed and new research avenues are suggested. Vincent Martel Sauvageau, Joël Macoir, Mélanie Langlois, Michel Prud’Homme, Léo Cantin, and Johanna-Pascale Roy Copyright © 2014 Vincent Martel Sauvageau et al. All rights reserved. Cognitive Status Correlates with CXCL10/IP-10 Levels in Parkinson’s Disease Wed, 15 Oct 2014 10:11:16 +0000 Cognitive impairment and depressive symptoms are of great interest in Parkinson’s disease (PD), since they are very common and lead to increased disability with poor quality of life. Inflammatory mechanisms have been implicated in PD and its nonmotor symptoms. In the current pilot study, we aimed to evaluate plasma levels of chemokines in PD patients and to analyze the putative association of chemokines with depressive symptoms and cognitive performance. We hypothesized that higher chemokines levels are associated with worse cognitive performance and increased depressive symptoms in PD. For this purpose, 40 PD patients and 25 age- and gender-matched controls were subjected to a clinical evaluation including cognitive and mood tests. Peripheral blood was drawn and plasma levels of CCL2/MCP-1, CCL11/eotaxin, CCL24/eotaxin-2, and CXCL10/IP-10 were measured by enzyme-linked immunosorbent assay. PD patients and control individuals presented comparable plasma concentrations of all the evaluated chemokines. In PD patients, CXCL10/IP-10 plasma levels correlated positively with Hoehn and Yahr staging scale. In addition, the higher CXCL10/IP-10 levels, the worse performance on cognitive tests. Although there was no significant difference between PD patients and control individuals regarding chemokines levels, our preliminary results showed that CXCL10/IP-10 may be associated with cognitive status in PD. Natália Pessoa Rocha, Paula Luciana Scalzo, Izabela Guimarães Barbosa, Mariana Soares Souza, Isabela Boechat Morato, Érica Leandro Marciano Vieira, Paulo Pereira Christo, Antônio Lúcio Teixeira, and Helton José Reis Copyright © 2014 Natália Pessoa Rocha et al. All rights reserved. Random Whole Body Vibration over 5 Weeks Leads to Effects Similar to Placebo: A Controlled Study in Parkinson’s Disease Mon, 13 Oct 2014 09:12:05 +0000 Background. Random whole body vibration (WBV) training leads to beneficial short-term effects in patients with Parkinson’s disease (PD). However, the effect of WBV lasting several weeks is not clear. Objectives. The aim of this study was to assess a random WBV training over 5 weeks in PD. Methods. Twenty-one participants with PD were allocated to either an experimental or a placebo group matched by age, gender, and Hoehn&Yahr stage. The WBV training consisted of 5 series, 60 s each. In the placebo group, vibration was simulated. The primary outcome was the change of performance in Functional reach test (FRT), step-walk-turn task, biomechanical Gait Analysis, Timed up and go test (TUG), and one leg stance. Findings. In most of the parameters, there was no significant interaction of “timegroup.” Both groups improved significantly in Gait parameters, TUG, and one leg stance. Only in the FRT [; ] and in the TUG [; ] the experimental group performed significantly better than the placebo group. Conclusions. Random WBV training over 5 weeks seems to be less effective than reported in previous studies performing short-term training. The slight improvements in the FRT and TUG are not clinically relevant. Heiko Gaßner, Annette Janzen, Ansgar Schwirtz, and Petra Jansen Copyright © 2014 Heiko Gaßner et al. All rights reserved. Are Branded and Generic Extended-Release Ropinirole Formulations Equally Efficacious? A Rater-Blinded, Switch-Over, Multicenter Study Tue, 26 Aug 2014 12:49:27 +0000 The aim of this study was to compare the efficacy of the branded and a generic extended-release ropinirole formulation in the treatment of advanced Parkinson’s disease (PD). Of 22 enrolled patients 21 completed the study. A rater blinded to treatment evaluated Unified Parkinson’s Disease Rating Scale, Fahn-Tolosa-Marin Tremor Rating Scale, Nonmotor Symptoms Assessment Scale, and a structured questionnaire on ropinirole side effects. Besides, the patients self-administered EQ-5D, Parkinson’s Disease Sleep Scale (PDSS-2), and Beck Depression Inventories. Branded and generic ropinirole treatment achieved similar scores on all tests measuring severity of motor symptoms (primary endpoint, UPDRS-III: 27.0 versus 28.0 points, ). Based on patient diaries, the lengths of “good time periods” were comparable (10.5 and 10.0 hours for branded and generic ropinirole, resp., ). However, generic ropinirole therapy achieved almost 3.0 hours shorter on time without dyskinesia (6.5 versus. 9.5 hours, ) and 2.5 hours longer on time with slight dyskinesia (3.5 versus. 1.0 hours, ) than the branded ropinirole did. Except for gastrointestinal problems, nonmotor symptoms were similarly controlled. Patients did not prefer either formulation. Although this study has to be interpreted with limitations, it demonstrated that both generic and branded ropinirole administration can achieve similar control on most symptoms of PD. Edit Bosnyák, Mihály Herceg, Endre Pál, Zsuzsanna Aschermann, József Janszky, Ildikó Késmárki, Sámuel Komoly, Kázmér Karádi, Tamás Dóczi, Ferenc Nagy, and Norbert Kovács Copyright © 2014 Edit Bosnyák et al. All rights reserved. Active Aging for Individuals with Parkinson’s Disease: Definitions, Literature Review, and Models Mon, 25 Aug 2014 05:24:42 +0000 Active aging has been emerged to optimize different aspects of health opportunities during the aging process in order to enhance quality of life. Yet, most of the efforts are on normal aging and less attention has been paid for the elderly suffering from a chronic illness such as Parkinson’s disease (PD). The aim of this review was to investigate how the concept of “active aging” fit for the elderly with PD and to propose a new model for them using the recent improvements in caring models and management approaches. For this purpose, biomedical databases have been assessed using relevant keywords to find out appropriate articles. Movement problems of PD affect physical activity, psychiatric symptoms lessen social communication, and cognitive impairment could worsen mental well-being in elderly with PD, all of which could lead to earlier retirement and poorer quality of life compared with healthy elderly. Based on the multisystematic nature of PD, a new “Active Aging Model for Parkinson’s Disease” is proposed consisting of self-care, multidisciplinary and interdisciplinary care, palliative care, patient-centered care, and personalized care. These strategies could potentially help the individuals with PD to have a better management approach for their condition towards the concept of active aging. Seyed-Mohammad Fereshtehnejad and Johan Lökk Copyright © 2014 Seyed-Mohammad Fereshtehnejad and Johan Lökk. All rights reserved. Executive Function and Postural Instability in People with Parkinson’s Disease Thu, 17 Jul 2014 09:54:42 +0000 The specific aspects of cognition contributing to balance and gait have not been clarified in people with Parkinson’s disease (PD). Twenty PD participants and twenty age- and gender-matched healthy controls were assessed on cognition and clinical mobility tests. General cognition was assessed with the Mini Mental State Exam and Addenbrooke’s Cognitive Exam. Executive function was evaluated using the Trail Making Tests (TMT-A and TMT-B) and a computerized cognitive battery which included a series of choice reaction time (CRT) tests. Clinical gait and balance measures included the Tinetti, Timed Up & Go, Berg Balance, and Functional Reach tests. PD participants performed significantly worse than the controls on the tests of cognitive and executive function, balance, and gait. PD participants took longer on Trail Making Tests, CRT-Location, and CRT-Colour (inhibition response). Furthermore, executive function, particularly longer times on CRT-Distracter and greater errors on the TMT-B, was associated with worse balance and gait performance in the PD group. Measures of general cognition were not associated with balance and gait measures in either group. For PD participants, attention and executive function were impaired. Components of executive function, particularly those involving inhibition response and distracters, were associated with poorer balance and gait performance in PD. Dong Xu, Michael H. Cole, Kerrie Mengersen, Peter A. Silburn, Feng Qiu, Cara Graepel, and Graham K. Kerr Copyright © 2014 Dong Xu et al. All rights reserved. Temporal Characteristics of High-Frequency Lower-Limb Oscillation during Freezing of Gait in Parkinson’s Disease Wed, 02 Jul 2014 09:32:00 +0000 A cardinal feature of freezing of gait (FOG) is high frequency (3–8 Hz) oscillation of the legs, and this study aimed to quantify the temporal pattern of lower-body motion prior to and during FOG. Acceleration data was obtained from sensors attached to the back, thighs, shanks, and feet in 14 Parkinson’s disease patients performing timed-up-and-go tasks, and clinical assessment of FOG was performed by two experienced raters from video. A total of 23 isolated FOG events, defined as occurring at least 5 s after gait initiation and with no preceding FOG, were identified from the clinical ratings. The corresponding accelerometer records were analyzed within a 4 s window centered at the clinical onset of freezing. FOG-related high-frequency oscillation (an increase in power in the 3–8 Hz band >3 SD from baseline) followed a distal to proximal onset pattern, appearing at the feet, shanks, thighs, and then back over a period of 250 ms. Peak power tended to decrease as the focus of oscillation moved from feet to back. There was a consistent delay (mean 872 ms) between the onset of high frequency oscillation at the feet and clinical onset of FOG. We infer that FOG is characterized by high frequency oscillation at the feet, which progresses proximally and is mechanically damped at the torso. Don A. Yungher, Tiffany R. Morris, Valentina Dilda, James M. Shine, Sharon L. Naismith, Simon J. G. Lewis, and Steven T. Moore Copyright © 2014 Don A. Yungher et al. All rights reserved. Neuroprotective Properties of a Standardized Extract from Myracrodruon urundeuva Fr. All. (Aroeira-Do-Sertão), as Evaluated by a Parkinson’s Disease Model in Rats Wed, 25 Jun 2014 10:28:14 +0000 Myracrodruon urundeuva Fr. All. (Anacardiaceae) is a Brazilian medicinal species, which is common to the Northeastern Brazilian semiarid region, whose stem-bark is widely used in folk medicine. It is an endangered species, presenting as main bioactive components tannins and chalcones. In this work, we studied the neuroprotective effects of a standardized extract from cultivated M. urundeuva (SEMU), in a model of Parkinson’s disease. Thus, a unilateral injection of 6-OHDA was done into the rat right stratum. The animals were submitted to stereotaxic surgery, then treated with SEMU (5, 10, 20, or 40 mg/kg, p.o.) for 2 weeks, subjected to behavioral tests, and euthanized for striata dissections and neurochemical, histological, and immunohistochemical analyses. We showed, for the first time, that SEMU reverted behavioral alterations seen in the 6-OHDA-lesioned group and partially blocked the decrease in DA and DOPAC contents. The numbers of viable neurons and TH immunopositive cells were increased by SEMU. In addition, the SEMU-treated 6-OHDA groups showed lower numbers of GFAP and OX-42 immunopositive cells. The neuroprotective action of SEMU is possibly related to the antioxidant and anti-inflammatory properties of M. urundeuva, pointing out to its potential use in the prevention or treatment of neurodegenerative conditions, such as Parkinson’s disease. Iana Calou, Mary Anne Bandeira, Wellida Aguiar-Galvão, Gilberto Cerqueira, Rafaelly Siqueira, Kelly Rose Neves, Gerly Anne Brito, and Glauce Viana Copyright © 2014 Iana Calou et al. All rights reserved. Serum Leptin Concentrations in Turkish Parkinson’s Disease Population Mon, 28 Apr 2014 08:05:10 +0000 Objectives. To investigate leptin levels and their relationship to body composition and demographic and clinical characteristics of Turkish patients with Parkinson’s disease (PD). Patients and Methods. Forty eligible PD patients and 25 healthy controls were included in the study. Body composition measurements (height, weight, waist circumference (WC), and body mass index (BMI)) of the whole sample and clinical findings of PD patients were evaluated in the on-state. A single 5 mL fasting blood sample was obtained from each participant in the morning. Severity of PD was evaluated using the Hoehn and Yahr scale and the Unified Parkinson’s Disease Rating Scale. Results. The mean age of the patients and controls was and years, while the mean BMI was and and the mean leptin levels were and  ng/mL, respectively. Only age and gender were correlated with leptin levels. There was a significant difference () in leptin levels between male ( ng/mL) and female ( ng/mL) PD patients. Among the male PD patients, older age and higher BMI and WC values were associated with higher mean leptin levels. There was not any significant relationship between leptin levels and clinical findings in PD patients. Conclusion. These results may suggest that leptin levels have no determinative role in the follow-up of PD patients with regard to the severity and clinical prognosis of PD. Betul Ozdilek and Gulay Kenangil Copyright © 2014 Betul Ozdilek and Gulay Kenangil. All rights reserved. Dopamine Cytotoxicity Involves Both Oxidative and Nonoxidative Pathways in SH-SY5Y Cells: Potential Role of Alpha-Synuclein Overexpression and Proteasomal Inhibition in the Etiopathogenesis of Parkinson's Disease Wed, 02 Apr 2014 13:27:56 +0000 Background. The cytotoxic effects of dopamine (DA) on several catecholaminergic cell lines involve DA oxidation products like reactive oxygen species (ROS) and toxic quinones and have implications in the pathogenesis of sporadic Parkinson's disease (PD). However, many molecular details are yet to be elucidated, and the possible nonoxidative mechanism of dopamine cytotoxicity has not been studied in great detail. Results. Cultured SH-SY5Y cells treated with DA (up to 400 M) or lactacystin (5 M) or DA (400 M) plus N-acetylcysteine (NAC, 2.5 mM) for 24 h are processed accordingly to observe the cell viability, mitochondrial dysfunctions, oxidative stress parameters, proteasomal activity, expression of alpha-synuclein gene, and intracellular accumulation of the protein. DA causes mitochondrial dysfunction and extensive loss of cell viability partially inhibited by NAC, potent inhibition of proteasomal activity marginally prevented by NAC, and overexpression with accumulation of intracellular alpha-synuclein partially preventable by NAC. Under similar conditions of incubation, NAC completely prevents enhanced production of ROS and increased formation of quinoprotein adducts in DA-treated SH-SY5Y cells. Separately, proteasomal inhibitor lactacystin causes accumulation of alpha-synuclein as well as mitochondrial dysfunction and cell death. Conclusions. DA cytotoxicity includes both oxidative and nonoxidative modes and may involve overexpression and accumulation of alpha-synuclein as well as proteasomal inhibition. Kalpita Banerjee, Soumyabrata Munshi, Oishimaya Sen, Vishmadeb Pramanik, Tapasi Roy Mukherjee, and Sasanka Chakrabarti Copyright © 2014 Kalpita Banerjee et al. All rights reserved. Minimal Clinically Important Difference in Parkinson’s Disease as Assessed in Pivotal Trials of Pramipexole Extended Release Tue, 01 Apr 2014 12:28:38 +0000 Background. The minimal clinically important difference (MCID) is the smallest change in an outcome measure that is meaningful for patients. Objectives. To calculate the MCID for Unified Parkinson’s Disease Rating Scale (UPDRS) scores in early Parkinson’s disease (EPD) and for UPDRS scores and “OFF” time in advanced Parkinson’s disease (APD). Methods. We analyzed data from two pivotal, double-blind, parallel-group trials of pramipexole ER that included pramipexole immediate release (IR) as an active comparator. We calculated MCID as the mean change in subjects who received active treatment and rated themselves “a little better” on patient global impression of improvement (PGI-I) minus the mean change in subjects who received placebo and rated themselves unchanged. Results. MCIDs in EPD (pramipexole ER, pramipexole IR) for UPDRS II were −1.8 and −2.0, for UPDRS III −6.2 and −6.1, and for UPDRS II + III −8.0 and −8.1. MCIDs in APD for UPDRS II were −1.8 and −2.3, for UPDRS III −5.2 and −6.5, and for UPDRS II + III −7.1 and −8.8. MCID for “OFF” time (pramipexole ER, pramipexole IR) was −1.0 and −1.3 hours. Conclusions. A range of MCIDs is emerging in the PD literature that provides the basis for power calculations and interpretation of clinical trials. Robert A. Hauser, Mark Forrest Gordon, Yoshikuni Mizuno, Werner Poewe, Paolo Barone, Anthony H. Schapira, Olivier Rascol, Catherine Debieuvre, and Mandy Fräßdorf Copyright © 2014 Robert A. Hauser et al. All rights reserved. Nonmotor Symptoms in a Malaysian Parkinson’s Disease Population Tue, 01 Apr 2014 07:52:09 +0000 Background. The nonmotor symptoms are important determinants of health and quality of life in Parkinson’s disease but are not well recognized and addressed in clinical practice. This study was conducted to determine the prevalence of nonmotor symptoms and their impact on quality of life in patients with Parkinson’s disease. Methods. This was a cross-sectional study among patients with idiopathic Parkinson’s disease. Exclusion criteria were a Mini Mental State Examination score of <21/30. Prevalence of nonmotor symptoms was determined using the NMSQuest. The severity of nonmotor symptoms and the quality of life were assessed using validated disease-specific questionnaires (PDQ-39 and NMSS). Results. A total of 113 patients consisting of 60 males and 53 females were recruited. The median duration of illness was 5.0 (2.0–8.0) years. The prevalence rate of nonmotor symptoms in our cohort was 97.3%. The most common reported nonmotor symptom in our cohort was gastrointestinal (76.1%). We found that the severity of the nonmotor symptoms was associated with poorer quality of life scores (: 0.727, ). Conclusions. Nonmotor symptoms were highly prevalent in our patients with Parkinson’s disease and adversely affected the quality of life of our patients. In contrast to western studies, the most common nonmotor symptom is gastrointestinal. The possibility of an Asian diet playing a role in this observation requires further study. Shahrul Azmin, Abdul Manaf Khairul Anuar, Hui Jan Tan, Wan Yahya Nafisah, Azman Ali Raymond, Othman Hanita, Shamsul Azhar Shah, and Mohamed Ibrahim Norlinah Copyright © 2014 Shahrul Azmin et al. All rights reserved. Neuropsychiatric Symptoms in an Inpatient Parkinson’s Disease Sample Wed, 12 Mar 2014 11:37:19 +0000 Background. Neuropsychiatric symptoms are common in idiopathic Parkinson’s disease (PD), and hospitalization for delirium, depression, psychosis, and anxiety is sometimes required. A minimal amount of data exists on these patients. Methods. Charts of all patients admitted to a psychiatric hospital between 2006 and 2009 with a diagnosis of PD were reviewed. Forty-three met entry criteria and were reviewed. Initial and discharge diagnoses, comorbid psychiatric diagnoses, length of stay, and living arrangements before and after hospitalization are described. Results. Consistent with previous research, this study showed evidence of comorbid psychiatric disorders within PD. Conclusions. The long-term goal of this area of study would be to reduce neuropsychiatric symptoms and improve quality of life in order to reduce inpatient hospital stays. Nicole C. R. McLaughlin, Irene Piryatinsky, Gary Epstein-Lubow, Louis Marino, and Joseph H. Friedman Copyright © 2014 Nicole C. R. McLaughlin et al. All rights reserved. Trends in Antiparkinsonian Medication Use in New Zealand: 1995–2011 Tue, 04 Mar 2014 12:58:17 +0000 Prescribing trends for medications are influenced by development of new drugs, changes in knowledge about efficacy and side effects, and priorities set by funding agencies. Changes in the utilization of antiparkinsonian agents in the outpatient community in New Zealand were investigated by using the national prescription database for the period 1995–2011. The dispensed volumes of antiparkinsonian agents were converted into number of defined daily doses per 1000 inhabitants per day for analysis. Increases in the dispensed volumes of levodopa (77%), amantadine (350%), and catechol-o-methyl transferase inhibitors (326%) occurred during the study period. Conversely, decreases in the dispensed volumes of anticholinergics (48%), selegiline (82%), and dopamine agonists (6.2%) were observed. New Zealand has seen a substantial increase of the amount of levodopa dispensed in the past 17 years. This increase appears to be related to an increase in the number of people taking the medication. We are unable to extrapolate this change to an increase in the prevalence of PD, given levodopa is used in the treatment of a number of medical conditions. The changes in other antiparkinsonian medications largely reflect changes in availability (increases in entacapone and ropinirole) and best practice treatment (declines in anticholinergics, selegiline, and tolcapone). T. L. Pitcher, M. R. MacAskill, and T. J. Anderson Copyright © 2014 T. L. Pitcher et al. All rights reserved.