Parkinson’s Disease The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. The Influence of Parkinson’s Disease Motor Symptom Asymmetry on Hand Performance: An Examination of the Grooved Pegboard Task Thu, 26 Nov 2015 12:00:55 +0000 This study examined the influence of motor symptom asymmetry in Parkinson’s disease (PD) on Grooved Pegboard (GP) performance in right-handed participants. The Unified Parkinson’s Disease Rating Scale was used to assess motor symptoms and separate participants with PD into two groups (right-arm affected, left-arm affected) for comparison with a group of healthy older adults. Participants completed the place and replace GP tasks two times with both hands. Laterality quotients were computed to quantify performance differences between the two hands. Comparisons among the three groups indicated that when the nonpreferred hand is affected by PD motor symptoms, superior preferred hand performance (as seen in healthy older adults) is further exaggerated in tasks that require precision (i.e., place task). Regardless of the task, when the preferred hand is affected, there is an evident shift to superior left-hand performance, which may inevitably manifest as a switch in hand preference. Results add to the discussion of the relationship between handedness and motor symptom asymmetry in PD. Sara M. Scharoun, Pamela J. Bryden, Michael D. Sage, Quincy J. Almeida, and Eric A. Roy Copyright © 2015 Sara M. Scharoun et al. All rights reserved. Acute and Chronic Effect of Acoustic and Visual Cues on Gait Training in Parkinson’s Disease: A Randomized, Controlled Study Thu, 26 Nov 2015 06:49:17 +0000 In this randomized controlled study we analyse and compare the acute and chronic effects of visual and acoustic cues on gait performance in Parkinson’s Disease (PD). We enrolled 46 patients with idiopathic PD who were assigned to 3 different modalities of gait training: (1) use of acoustic cues, (2) use of visual cues, or (3) overground training without cues. All patients were tested with kinematic analysis of gait at baseline (T0), at the end of the 4-week rehabilitation programme (T1), and 3 months later (T2). Regarding the acute effect, acoustic cues increased stride length and stride duration, while visual cues reduced the number of strides and normalized the stride/stance distribution but also reduced gait speed. As regards the chronic effect of cues, we recorded an improvement in some gait parameters in all 3 groups of patients: all 3 types of training improved gait speed; visual cues also normalized the stance/swing ratio, acoustic cues reduced the number of strides and increased stride length, and overground training improved stride length. The changes were not retained at T2 in any of the experimental groups. Our findings support and characterize the usefulness of cueing strategies in the rehabilitation of gait in PD. Roberto De Icco, Cristina Tassorelli, Eliana Berra, Monica Bolla, Claudio Pacchetti, and Giorgio Sandrini Copyright © 2015 Roberto De Icco et al. All rights reserved. Knowledge and Attitudes of Parkinson’s Disease in Rural and Urban Mukono District, Uganda: A Cross-Sectional, Community-Based Study Wed, 25 Nov 2015 06:47:27 +0000 Background. Parkinson’s disease (PD) negatively affects the quality of life. There is limited information on PD published from Africa. Lack of adequate knowledge poses a barrier in the provision of appropriate treatment and care for individuals with PD. Methods. A cross-sectional survey was conducted in urban and rural Mukono district, central Uganda. Through the systematic sampling method, data were gathered from 377 adult participants, interviewed on selected aspects of PD knowledge and attitudes. Results. Of the 377 participants, 47% were from urban settings and 68% (260/377) were women with a median age (IQR) of 34 (26–48) years. Half of the study respondents did not know the body part involved in or apparent cause of PD. Nearly 1/3 of individuals believed that PD is a form of insanity and 17% believed that PD is contagious. Rural dwellers were more likely to have incorrect knowledge regarding selected aspects of PD. Conclusions. Understanding the cause of PD is very limited in our setting. Some beliefs about PD aetiology may potentially worsen stigma and social isolation. This study highlights the need for increasing PD awareness in our settings. Public health approaches that improve knowledge are urgently needed to promote care access and community response to Parkinson’s disease. Mark Kaddumukasa, Angelina Kakooza, Martin N. Kaddumukasa, Edward Ddumba, Levi Mugenyi, Martha Sajatovic, and Elly Katabira Copyright © 2015 Mark Kaddumukasa et al. All rights reserved. Pisa Syndrome in Parkinson’s Disease: Electromyographic Aspects and Implications for Rehabilitation Mon, 23 Nov 2015 11:20:37 +0000 Pisa Syndrome (PS) is a real clinical enigma, and its management remains a challenge. In order to improve the knowledge about resting state and during maximal voluntary muscle contraction (MVMC) of the axial muscles, we described the electromyography results of paraspinal muscles, rectus abdominis, external oblique, and quadratus lumborum of both sides of 60 patients. Electromyography was assessed at rest, during MVMC while bending in the opposite direction of the PS and during MVMC while bending in the direction of the PS. The MVMC gave information about the interferential pattern (INT) or subinterferential pattern (sub-INT). We defined asymmetrical activation (AA) when a sub-INT was detected on the muscle on the side opposite to the PS bending and an INT of same muscle in the direction of PS bending. We observed significant AA during MVMC only in the external oblique muscles in 78% of the subjects. Our results of asymmetric ability to generate maximal voluntary force of the external oblique muscles support a central dissynchronisation of axial muscles as a significant contributor for the bending of the spine in erect position. These results could have important implication to physiotherapy and the use of botulinum toxin in the treatment of PS. Giuseppe Frazzitta, Pietro Balbi, Francesco Gotti, Roberto Maestri, Annarita Sabetta, Luca Caremani, Laura Gobbi, Marina Capobianco, Rossana Bera, Nir Giladi, and Davide Ferrazzoli Copyright © 2015 Giuseppe Frazzitta et al. All rights reserved. Impact of Impulse Control Disorders on Sleep-Wake Regulation in Parkinson’s Disease Wed, 18 Nov 2015 11:52:05 +0000 Sleep disturbances are common in patients with Parkinson’s disease (PD) and are even more prevalent in patients with behavioural addictions, such as pathological gambling, compulsive sexual behaviour, compulsive buying, binge eating, punding, and the compulsive use of dopamine replacement therapy. An overview of the relationship between these impulse control disorders and sleep disturbances is given and potential underlying mechanisms and treatment strategies are covered. Atbin Djamshidian, Werner Poewe, and Birgit Högl Copyright © 2015 Atbin Djamshidian et al. All rights reserved. Enhanced Neuroprotective Effects of Coadministration of Tetrandrine with Glutathione in Preclinical Model of Parkinson’s Disease Wed, 18 Nov 2015 09:16:37 +0000 Aim. In this study we examined the influence of tetrandrine (Tet) on the neuroprotective effects of glutathione (GSH) in the 6-hydroxydopamine- (6-OHDA-) lesioned rat model of Parkinson’s disease (PD). Methods. Levels in the redox system, dopamine (DA) metabolism, dopaminergic neuronal survival, and apoptosis of the substantia nigra (SN) and striatum, as well as the rotational behavior of animals were examined after a 50-day administration of GSH + Tet (or GSH) and/or L-3,4-dihydroxyphenylalanine (L-dopa) to PD rats. Ethics Committee of Huashan Hospital, Fudan University approved the protocol (number SYXK2009-0082). Results. Administration of GSH or Tet alone did not show any significant effects on the factors evaluated in the PD rats. However, in the GSH + Tet group, we observed markedly decreased oxidative damage, inhibition of DA metabolism and enhanced DA synthesis, increased tyrosine hydroxylase- (TH-) immunopositive neuronal survival, and delayed apoptosis of dopaminergic neurons in the SN. Animal rotational behavior was improved in the GSH + Tet group. Additionally, coadministration of GSH + Tet appeared to offset the possible oxidative neurotoxicity induced by L-dopa. Conclusion. In this study, we demonstrated that tetrandrine allowed occurrence of the neuroprotective effect of glutathione probably due to inhibition of P-glycoprotein on 6-hydroxydopamine-lesioned rat models of Parkinson’s disease, including rats undergoing long-term L-dopa treatment. Xiang-Yun Li, Guang-Hai Mei, Qiang Dong, Yu Zhang, Zhuang-Li Guo, Jing-Jing Su, Yu-Ping Tang, Xue-Hong Jin, Hou-Guang Zhou, and Yan-Yan Huang Copyright © 2015 Xiang-Yun Li et al. All rights reserved. Potential of Neural Stem Cell-Based Therapy for Parkinson’s Disease Tue, 17 Nov 2015 13:19:34 +0000 Neural stem cell (NSC) transplantation is an emerging strategy for restoring neuronal function in neurological disorders, such as Parkinson’s disease (PD), which is characterized by a profound and selective loss of nigrostriatal dopaminergic (DA) neurons. Adult neurogenesis generates newborn neurons that can be observed at specialized niches where endothelial cells (ECs) play a significant role in regulating the behavior of NSCs, including self-renewal and differentiating into all neural lineage cells. In this minireview, we highlight the importance of establishing an appropriate microenvironment at the target site of NSC transplantation, where grafted cells integrate into the surroundings in order to enhance DA neurotransmission. Using a novel model of NSC-EC coculture, it is possible to combine ECs with NSCs, to generate such a neurovascular microenvironment. With appropriate NSCs selected, the composition of the transplant can be investigated through paracrine and juxtacrine signaling within the neurovascular unit (NVU). With target site cellular and acellular compartments of the microenvironment recognized, guided DA differentiation of NSCs can be achieved. As differentiated DA neurons integrate into the existing nigrostriatal DA pathway, the symptoms of PD can potentially be alleviated by reversing characteristic neurodegeneration. Chung-Hsing Chou, Hueng-Chuen Fan, and Dueng-Yuan Hueng Copyright © 2015 Chung-Hsing Chou et al. All rights reserved. Myocardial 123I-MIBG Uptake and Cardiovascular Autonomic Function in Parkinson’s Disease Sun, 15 Nov 2015 10:00:32 +0000 Introduction. Patients with Parkinson’s disease (PD) showed reduced myocardial 123I-MIBG uptake, which may affect autonomic regulation. We investigated correlation between MIBC accumulation and cardiovascular autonomic function in PD. Methods. We performed myocardial MIBG scintigraphy, heart rate variability (HRV) analysis, and the head-up tilt test (HUT) in 50 PD patients ( years; duration years). Autonomic function tests were also performed in 50 healthy controls ( years). As HRV parameters, a high-frequency power (HF, 0.15–0.4 Hz), a low-frequency power (LF, 0.04–0.15 Hz), and LF/HF ratio were used. Results. Our PD patients had a significant reduction in LF and HF compared with the controls ( and ). In HUT, systolic and diastolic blood pressure falls in the PD group were significantly greater than those in the controls ( and ). The washout rate of MIBG was negatively correlated with blood pressure changes during HUT. Conclusion. Our PD patients showed reduced HRV, blood pressure dysregulation, and reduced MIBG accumulation, which was correlated with blood pressure dysregulation. Orthostatic hypotension in PD may be mainly caused by sympathetic postganglionic degeneration. Akira Katagiri, Masato Asahina, Nobuyuki Araki, Anupama Poudel, Yoshikatsu Fujinuma, Yoshitaka Yamanaka, and Satoshi Kuwabara Copyright © 2015 Akira Katagiri et al. All rights reserved. Impact of Deep Brain Stimulation on Daily Routine Driving Practice in Patients with Parkinson’s Disease Tue, 10 Nov 2015 14:26:54 +0000 Objective. To determine the influence of deep brain stimulation (DBS) on daily routine driving behavior in Parkinson’s disease (PD) patients. Methods. A cross-sectional questionnaire survey was done in 121 DBS-PD patients. The influences of patient characteristics and DBS on current driving and driving at time of surgery and the predictive value of the preoperative levodopa-test on postoperative driving were evaluated. Results. 50% of 110 driving-license holders currently drove. 63.0% rated themselves as safe drivers, 39.4% reported improvement, and 10.9% noted deterioration in driving after DBS surgery. Inactive drivers had quit driving mainly due to disease burden (90.9%). Active drivers were younger, more often males, and less impaired according to H&Y and MMSE, had surgery more recently, and reported more often overall benefit from DBS. H&Y “on” and UPDRS III “off” scores at time of surgery were lower in pre- and postoperative active than in inactive drivers. Tremor and akinesia were less frequent reasons to quit driving after than before DBS surgery. Postoperatively, 22.7% (10/44) of patients restarted and 10.6% (7/66) of patients discontinued driving, independently of H&Y stage. The preoperative levodopa-test was not predictive for the postoperative driving outcome. Conclusion. 50% of PD patients with DBS drive. DBS surgery changes daily routine driving behavior. Carsten Buhmann, Eik Vettorazzi, Christian Oehlwein, Fred Rikkers, Monika Poetter-Nerger, Alessandro Gulberti, Christian Gerloff, Christian K. Moll, and Wolfgang Hamel Copyright © 2015 Carsten Buhmann et al. All rights reserved. Four Copies of SNCA Responsible for Autosomal Dominant Parkinson’s Disease in Two Italian Siblings Mon, 09 Nov 2015 09:26:33 +0000 Background. Parkinson’s disease (PD) is mostly characterized by alpha-synuclein (SNCA) aggregation and loss of nigrostriatal dopamine-containing neurons. In this study a novel SNCA multiplication is described in two siblings affected by severe parkinsonism featuring early onset dyskinesia, psychiatric symptoms, and cognitive deterioration. Methods. SNCA dosage was performed using High-Density Comparative Genomic Hybridization Array (CGH-Array), Multiple Ligation Dependent Probe Amplification (MLPA), and Quantitative PCR (qPCR). Genetic analysis was associated with clinical evaluation. Results. Genetic analysis of siblings showed for the first time a 351 Kb triplication containing SNCA gene along with 6 exons of MMRN1 gene in 4q22.1 and a duplication of 1,29 Mb of a genomic region flanking the triplication. Conclusions. The identification of this family indicates a novel mechanism of SNCA gene multiplication, which confirms the genomic instability in this region and provides data on the genotype-phenotype correlation in PD patients. Rosangela Ferese, Nicola Modugno, Rosa Campopiano, Marco Santilli, Stefania Zampatti, Emiliano Giardina, Annamaria Nardone, Diana Postorivo, Francesco Fornai, Giuseppe Novelli, Edoardo Romoli, Stefano Ruggieri, and Stefano Gambardella Copyright © 2015 Rosangela Ferese et al. All rights reserved. Screening for Mild Cognitive Impairment in Parkinson’s Disease: Comparison of the Italian Versions of Three Neuropsychological Tests Sun, 08 Nov 2015 10:00:29 +0000 Mild cognitive impairment (MCI) is frequent in Parkinson’s disease (PD). Recently proposed criteria for MCI in PD (PD-MCI) indicate level I diagnosis based on abbreviated assessment and level II based on comprehensive neuropsychological evaluation. The study explored the sensitivity and specificity of the Italian versions of three neuropsychological tests for level I diagnosis of PD-MCI. We recruited 100 consecutive PD patients. After screening for inclusion criteria, 43 patients were included. The sensitivity and specificity of the Mini Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), and the Addenbrooke’s Cognitive Examination Revised (ACE-R) in comparison to level II diagnosis of PD-MCI were examined. PD-MCI was diagnosed (level II) in 51% of patients. Disease duration was significantly longer and PD motor scales were more severely impaired in MCI group. The receiver-operator characteristics curve documented nonsignificant difference in the performance of the three tests, with slight advantage of MMSE (corrected data). The time of administration favored MMSE. In Italian-speaking PD patients, MMSE might represent a good screening tool for PD-MCI, because of the shorter time of administration and the performance comparable to those of MoCA and ACE-R. Further studies are needed to validate the new PD-MCI criteria across different languages and cultures. Angela Federico, Alice Maier, Greta Vianello, Daniela Mapelli, Michela Trentin, Giampietro Zanette, Alessandro Picelli, Marialuisa Gandolfi, and Stefano Tamburin Copyright © 2015 Angela Federico et al. All rights reserved. Abnormal Cerebrovascular Reactivity in Parkinson’s Disease Mon, 02 Nov 2015 14:19:32 +0000 Kiran Prakash Copyright © 2015 Kiran Prakash. All rights reserved. Association between Community Ambulation Walking Patterns and Cognitive Function in Patients with Parkinson’s Disease: Further Insights into Motor-Cognitive Links Thu, 29 Oct 2015 09:02:48 +0000 Background. Cognitive function is generally evaluated based on testing in the clinic, but this may not always reflect real-life function. We tested whether parameters derived from long-term, continuous monitoring of gait are associated with cognitive function in patients with Parkinson’s disease (PD). Methods. 107 patients with PD (age: 64.9 ± 9.3 yrs; UPDRS motor sum “off”: 40.4 ± 13.2; 25.23% women) wore a 3D accelerometer on their lower back for 3 days. Computerized measures of global cognitive function, executive function, attention, and nonverbal memory were assessed. Three-day acceleration derived measures included cadence, variability, bilateral coordination, and dynamic postural control. Associations between the acceleration derived measures and cognitive function were determined. Results. Linear regression showed associations between vertical gait variability and cadence and between global cognitive score, attention, and executive function (). Dynamic postural control was associated with global cognitive score and attention (). Nonverbal memory was not associated with the acceleration-derived measures. Conclusions. These findings suggest that metrics derived from a 3-day worn body-fixed sensor reflect cognitive function, further supporting the idea that the gait pattern may be altered as cognition declines and that gait provides a window into cognitive function in patients with PD. Aner Weiss, Talia Herman, Nir Giladi, and Jeffrey M. Hausdorff Copyright © 2015 Aner Weiss et al. All rights reserved. Effects of Night-Time Use of Rotigotine on Nocturnal Symptoms in Parkinson’s Disease Wed, 21 Oct 2015 11:53:39 +0000 Objectives. This open-label study assessed the efficacy and safety of exclusive night-time administration of transdermal rotigotine in patients with nocturnal and early morning PD symptoms. Methods. Patients with PD and nocturnal and early morning symptoms received transdermal rotigotine patches (2–16 mg/24 h) applied in the evening and removed in the morning for 3 months. Sleep disturbance was assessed with modified Parkinson’s Disease Sleep Scale (PDSS-2). Other outcomes included a pain visual analogue scale (VAS) and short-form Parkinson’s Disease Questionnaire (PDQ-8) for quality of life. Results. 74 patients completed treatment in this study. At the end of treatment, PDSS-2 total score had improved by mean 10.9 points from baseline (p < 0.001). All three PDSS-2 domain scores (sleep disturbances, nocturnal motor symptoms, and nocturnal symptoms) were also significantly improved by 41%, 56%, and 48%, respectively (p < 0.001). VAS-pain score decreased from 3.2 to 2.3 (p < 0.001). PDQ-8 score decreased from 23.8 to 18.1 (p < 0.001). The most frequently reported adverse events included nausea (9%), anxiety (4%), and dizziness (4%). Conclusions. Night-time administration of transdermal rotigotine is an effective and well tolerated treatment for nocturnal symptoms in patients with PD. Francesc Vallderiola, Yaroslau Compta, Javier Aparicio, Jaume Tarradellas, Gabriel Salazar, Josep María Oliver, Antonio Callén, Tania Delgado, and Fritz Nobbe Copyright © 2015 Francesc Vallderiola et al. All rights reserved. Mortality in Iranian Patients with Parkinson’s Disease: Cumulative Impact of Cardiovascular Comorbidities as One Major Risk Factor Tue, 20 Oct 2015 13:48:39 +0000 Mortality rate, life expectancy, survival, and the impact of comorbidities on them in people with Parkinson’s disease (PD) need to be assessed in settings with different sociodemographic backgrounds. We investigated mortality features in Iranian PD patients focusing on the role of cardiovascular multimorbidity on their survival. Data on mortality and comorbidity profile was gathered in a cohort of 190 individuals with idiopathic PD referred to a Movement Disorders Clinic. Standardized mortality ratio (SMR) compared to the Tehran general population was 3.44 and the life expectancy at birth was 67.4 (95% CI: 59.1–75.8) yr. Patients with at least one cardiovascular comorbidity had a shorter survival time after PD onset (14.0 versus 29.2 yr, ). The hazard ratio for death increased 2.8 times (95% CI: 1.5–5.2, ) with one additional cardiovascular comorbidity. Among all comorbid conditions, stroke showed the strongest independent effect on mortality in PD patients [HR = 13.1 (95% CI: 2.4–71.7), ]. Conclusively, life expectancy was slightly lower in Iranian PD patients compared to the general population, while the SMR was high. Cardiometabolic multimorbidity substantially decreased survival in people with PD. Our study highlights the need for assessment, prevention, and treatment of cardiovascular morbidities in parkinsonian patients, given their effect on survival. Seyed-Mohammad Fereshtehnejad, Azadeh Shafieesabet, Mahdiyeh Shafieesabet, Gholam Ali Shahidi, Ahmad Delbari, and Johan Lökk Copyright © 2015 Seyed-Mohammad Fereshtehnejad et al. All rights reserved. Diagnosis of Obstructive Sleep Apnea in Parkinson’s Disease Patients: Is Unattended Portable Monitoring a Suitable Tool? Tue, 13 Oct 2015 06:34:22 +0000 Purpose. Obstructive sleep apnea (OSA) is frequent in Parkinson’s disease (PD) and may contribute to nonmotor symptoms. Polysomnography (PSG) is the gold standard for OSA diagnosis. Unattended portable monitoring (PM) may improve access to diagnosis but has not been studied in PD. We assessed feasibility and diagnostic accuracy in PD. Methods. Selected PD patients without known OSA underwent home PM and laboratory PSG. The quality of PM signals (n = 28) was compared with matched controls. PM accuracy was calculated compared with PSG for standard apnea hypopnea index (AHI) thresholds. Results. Technical failure rate was 27.0% and airflow signal quality was lower than in controls. Sensitivity of PM was 84.0%, 36.4%, and 50.0% for AHI cut-offs of 5/h, 15/h, and 30/h, respectively, using the same cut-offs on PM. Specificity was 66.7%, 83.3%, and 100%, respectively. PM underestimated the AHI with a mean bias of 12.4/h. Discrepancy between PM and PSG was greater in those with more motor dysfunction. Conclusion. PM was adequate to “rule in” moderate or severe OSA in PD patients, but the failure rate was relatively high and signal quality poorer than in controls. PM overall underestimated the severity of OSA in PD patients, especially those with greater motor dysfunction. Priti Gros, Victoria P. Mery, Anne-Louise Lafontaine, Ann Robinson, Andrea Benedetti, R. John Kimoff, and Marta Kaminska Copyright © 2015 Priti Gros et al. All rights reserved. Assessment of Nonverbal and Verbal Apraxia in Patients with Parkinson’s Disease Mon, 12 Oct 2015 09:54:28 +0000 Objective. To assess the presence of nonverbal and verbal apraxia in patients with Parkinson’s disease (PD) and analyze the correlation between these conditions and patient age, education, duration of disease, and PD stage, as well as evaluate the correlation between the two types of apraxia and the frequency and types of verbal apraxic errors made by patients in the sample. Method. This was an observational prevalence study. The sample comprised 45 patients with PD seen at the Movement Disorders Clinic of the Clinical Hospital of Porto Alegre, Brazil. Patients were evaluated using the Speech Apraxia Assessment Protocol and PD stages were classified according to the Hoehn and Yahr scale. Results. The rate of nonverbal apraxia and verbal apraxia in the present sample was 24.4%. Verbal apraxia was significantly correlated with education (). The most frequent types of verbal apraxic errors were omissions (70.8%). The analysis of manner and place of articulation showed that most errors occurred during the production of trill (57.7%) and dentoalveolar (92%) phonemes, consecutively. Conclusion. Patients with PD presented nonverbal and verbal apraxia and made several verbal apraxic errors. Verbal apraxia was correlated with education levels. Monia Presotto, Maira Rozenfeld Olchik, Artur Francisco Shumacher Shuh, and Carlos R. M. Rieder Copyright © 2015 Monia Presotto et al. All rights reserved. Minimal Clinically Important Difference on Parkinson’s Disease Sleep Scale 2nd Version Sun, 11 Oct 2015 11:28:31 +0000 Background and Aims. The aim of the present study was to determine the estimates of minimal clinically important difference for Parkinson’s Disease Sleep Scale 2nd version (PDSS-2) total score and dimensions. Methods. The subject population consisted of 413 PD patients. At baseline, MDS-UPDRS, Hoehn-Yahr Scale, Mattis Dementia Rating Scale, and PDSS-2 were assessed. Nine months later the PDSS-2 was reevaluated with the Patient-Reported Global Impression Improvement Scale. Both anchor-based techniques (within patients’ score change method and sensitivity- and specificity-based method by receiver operating characteristic analysis) and distribution-based approaches (effect size calculations) were utilized to determine the magnitude of minimal clinically important difference. Results. According to our results, any improvements larger than −3.44 points or worsening larger than 2.07 points can represent clinically important changes for the patients. These thresholds have the effect size of 0.21 and −0.21, respectively. Conclusions. Minimal clinically important differences are the smallest change of scores that are subjectively meaningful to patients. Studies using the PDSS-2 as outcome measure should utilize the threshold of −3.44 points for detecting improvement or the threshold of 2.07 points for observing worsening. Krisztina Horváth, Zsuzsanna Aschermann, Péter Ács, Gabriella Deli, József Janszky, Sámuel Komoly, Kázmér Karádi, Márton Kovács, Attila Makkos, Béla Faludi, and Norbert Kovács Copyright © 2015 Krisztina Horváth et al. 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.