Parkinson’s Disease The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Parkinson’s Disease and Home Healthcare Use and Expenditures among Elderly Medicare Beneficiaries Sun, 24 May 2015 11:41:11 +0000 This study estimated excess home healthcare use and expenditures among elderly Medicare beneficiaries (age ≥ 65 years) with Parkinson’s disease (PD) compared to those without PD and analyzed the extent to which predisposing, enabling, need factors, personal health choice, and external environment contribute to the excess home healthcare use and expenditures among individuals with PD. A retrospective, observational, cohort study design using Medicare 5% sample claims for years 2006-2007 was used for this study. Logistic regressions and Ordinary Least Squares regressions were used to assess the association of PD with home health use and expenditures, respectively. Postregression nonlinear and linear decomposition techniques were used to understand the extent to which differences in home healthcare use and expenditures among elderly Medicare beneficiaries with and without PD can be explained by individual-level factors. Elderly Medicare beneficiaries with PD had higher home health use and expenditures compared to those without PD. 27.5% and 18% of the gap in home health use and expenditures, respectively, were explained by differences in characteristics between the PD and no PD groups. A large portion of the differences in home healthcare use and expenditures remained unexplained. Sandipan Bhattacharjee, Aaron Metzger, Cindy Tworek, Wenhui Wei, Xiaoyun Pan, and Usha Sambamoorthi Copyright © 2015 Sandipan Bhattacharjee et al. All rights reserved. Effects of Age and Gender on Hand Motion Tasks Sun, 24 May 2015 07:12:57 +0000 Objective. Wearable and wireless motion sensor devices have facilitated the automated computation of speed, amplitude, and rhythm of hand motion tasks. The aim of this study is to determine if there are any biological influences on these kinematic parameters. Methods. 80 healthy subjects performed hand motion tasks twice for each hand, with movements measured using a wireless motion sensor device (Kinesia, Cleveland Medical Devices Inc., Cleveland, OH). Multivariate analyses were performed with age, gender, and height added into the model. Results. Older subjects performed poorer in finger tapping (FT) speed (, ), hand-grasp (HG) speed (, ), and pronation-supination (PS) speed (, ). Men performed better in FT rhythm , HG speed , HG amplitude , and HG rhythm . Taller subjects performed better in the speed and amplitude components of FT and HG tasks . After multivariate analyses, only age and gender emerged as significant independent factors influencing the speed but not the amplitude and rhythm components of hand motion tasks. Gender exerted an independent influence only on HG speed, with better performance in men . Conclusions. Age, gender, and height are not independent factors influencing the amplitude and rhythm components of hand motion tasks. The speed component is affected by age and gender differences. Wing Lok Au, Irene Soo Hoon Seah, Wei Li, and Louis Chew Seng Tan Copyright © 2015 Wing Lok Au et al. All rights reserved. Person-Centered Care in the Home Setting for Parkinson’s Disease: Operation House Call Quality of Care Pilot Study Tue, 19 May 2015 10:30:59 +0000 Objective. (1) To evaluate the feasibility of implementing and evaluating a home visit program for persons with Parkinson’s disease (PD) in a rural setting. (2) To have movement disorders fellows coordinate and manage health care delivery. Background. The University of Florida, Center for Movement Disorders and Neurorestoration established Operation House Call to serve patients with PD who could not otherwise afford to travel to an expert center or to pay for medical care. PD is known to lead to significant disability, frequent hospitalization, early nursing home placement, and morbidity. Methods. This was designed as a quality improvement project. Movement disorders fellows travelled to the home(s) of underserved PD patients and coordinated their clinical care. The diagnosis of Parkinson’s disease was confirmed using standardized criteria, and the Unified Parkinson’s Disease Rating Scale was performed and best treatment practices were delivered. Results. All seven patients have been followed up longitudinally every 3 to 6 months in the home setting, and they remain functional and independent. None of the patients have been hospitalized for PD related complications. Each patient has a new updatable electronic medical record. All Operation House Call cases are presented during video rounds for the interdisciplinary PD team to make recommendations for care (neurology, neurosurgery, neuropsychology, psychiatry, physical therapy, occupational therapy, speech therapy, and social work). One Operation House Call patient has successfully received deep brain stimulation (DBS). Conclusion. This program is a pilot program that has demonstrated that it is possible to provide person-centered care in the home setting for PD patients. This program could provide a proof of concept for the construction of a larger visiting physician or nurse program. Nawaz Hack, Umer Akbar, Erin H. Monari, Amanda Eilers, Amanda Thompson-Avila, Nelson H. Hwynn, Ashok Sriram, Ihtsham Haq, Angela Hardwick, Irene A. Malaty, and Michael S. Okun Copyright © 2015 Nawaz Hack et al. All rights reserved. Pharmacokinetic Study and Optimal Formulation of New Anti-Parkinson Natural Compound Schisantherin A Sun, 17 May 2015 08:57:49 +0000 Our recent studies showed that schisantherin A (StA) is a promising candidate for PD treatment, but the pharmacokinetic profile of StA is largely unknown. The effects of different formulations on the pharmacokinetics and bioavailability of StA were investigated by HPLC equipped with a vacuum degasser, a quaternary pump, a manual sampler, and an ultraviolet detector. The absolute bioavailability of StA in nanoemulsion formulation was significantly increased from 4.3% to 47.3%. To the best of our knowledge, this is the first report of absolute bioavailability for StA in rats and successful increase of bioavailability of StA by nanoemulsion formulation. The pharmacokinetic profiles of StA could be significantly improved by a safe nanoemulsion formulation. This study provides a successful example of advanced delivery system for improving the bioavailability of potential central nervous system (CNS) drug candidate with poor solubility. This novel approach could be an effective alternative solution to overcome the shortcomings of conventional poor drug delivery of CNS drugs. The results of present study not only indicate that StA has potential to be developed as a promising oral therapeutic agent for the management of PD but also shed light on novel way to improve bioavailability of PD drugs. Fei Sa, Bao Jian Guo, Sai Li, Zai Jun Zhang, Hok Man Chan, Ying Zheng, and Simon Ming Yuen Lee Copyright © 2015 Fei Sa et al. All rights reserved. Visual Hallucinations as Incidental Negative Effects of Virtual Reality on Parkinson’s Disease Patients: A Link with Neurodegeneration? Sun, 10 May 2015 09:53:21 +0000 We followed up a series of 23 Parkinson’s disease (PD) patients who had performed an immersive virtual reality (VR) protocol eight years before. On that occasion, six patients incidentally described visual hallucinations (VH) with occurrences of images not included in the virtual environment. Curiously, in the following years, only these patients reported the appearance of VH later in their clinical history, while the rest of the group did not. Even considering the limited sample size, we may argue that VR immersive systems can induce unpleasant effects in PD patients who are predisposed to a cognitive impairment. Giovanni Albani, Elisa Pedroli, Pietro Cipresso, Daniel Bulla, Veronica Cimolin, Astrid Thomas, Alessandro Mauro, and Giuseppe Riva Copyright © 2015 Giovanni Albani et al. All rights reserved. Association Analysis of COQ2 Variant in Dementia and Essential Tremor Wed, 22 Apr 2015 11:16:28 +0000 Objective. COQ2 mutations have been reported in Japanese multiple system atrophy (MSA) patients. We examined the role of COQ2 in patients with dementia and essential tremor (ET), two common neurodegenerative conditions. Materials & Methods. A total of 2064 subjects, including 560 patients with dementia, 466 patients with ET, and 1038 healthy controls, were included. Genotyping for the COQ2 V393A (T>C) was carried out. Odds ratio (OR) adjusted by age and gender, together with 95% confidence interval (CI), was reported by means of logistic regression. Results. The frequency of the polymorphic variant V393A heterozygous (T/C) was 2.7% in dementia, 1.1% in ET, and 2.5% in controls (OR = 0.70, 95% confidence interval is 0.29–1.72 for dementia, and OR = 0.47, 95% confidence interval is 0.17–1.31, for ET). There was no significant association between V393A variant with dementia and ET. Conclusion. There was no significant association between V393A variant with dementia and ET. COQ2 gene is unlikely to play a significant role in patients with dementia or ET in our population. Yin Xia Chao, Ebonne Yu Lin Ng, Huihua Li, Kandiah Nagaendran, Yuen Yih, Mei Sian Chong, Kumar M. Prakash, Louis Tan, Wing Lok Au, Yi Zhao, Zhi Dong Zhou, Murni Tio, Ratnagopal Pavanni, and Eng King Tan Copyright © 2015 Yin Xia Chao et al. All rights reserved. The Role of α-Synuclein and LRRK2 in Tau Phosphorylation Tue, 21 Apr 2015 13:17:01 +0000 There is now a considerable body of experimental evidence that Parkinson’s disease arises through physiological interaction of causative molecules, leading to tau pathology. In this review, we discuss the physiological role of α-synuclein and LRRK2 in the abnormal phosphorylation of tau. In addition, as recent reports have indicated that heat shock proteins- (HSPs-) inducing drugs can help to ameliorate neurodegenerative diseases associated with tau pathology, we also discuss therapeutic strategies for PD focusing on inhibition of α-synuclein- and LRRK2-associated tau phosphorylation by HSPs. Fumitaka Kawakami and Takafumi Ichikawa Copyright © 2015 Fumitaka Kawakami and Takafumi Ichikawa. All rights reserved. Neurophysiology of Drosophila Models of Parkinson’s Disease Wed, 15 Apr 2015 12:27:33 +0000 We provide an insight into the role Drosophila has played in elucidating neurophysiological perturbations associated with Parkinson’s disease- (PD-) related genes. Synaptic signalling deficits are observed in motor, central, and sensory systems. Given the neurological impact of disease causing mutations within these same genes in humans the phenotypes observed in fly are of significant interest. As such we observe four unique opportunities provided by fly nervous system models of Parkinson’s disease. Firstly, Drosophila models are instrumental in exploring the mechanisms of neurodegeneration, with several PD-related mutations eliciting related phenotypes including sensitivity to energy supply and vesicular deformities. These are leading to the identification of plausible cellular mechanisms, which may be specific to (dopaminergic) neurons and synapses rather than general cellular phenotypes. Secondly, models show noncell autonomous signalling within the nervous system, offering the opportunity to develop our understanding of the way pathogenic signalling propagates, resembling Braak’s scheme of spreading pathology in PD. Thirdly, the models link physiological deficits to changes in synaptic structure. While the structure-function relationship is complex, the genetic tractability of Drosophila offers the chance to separate fundamental changes from downstream consequences. Finally, the strong neuronal phenotypes permit relevant first in vivo drug testing. Ryan J. H. West, Rebecca Furmston, Charles A. C. Williams, and Christopher J. H. Elliott Copyright © 2015 Ryan J. H. West et al. All rights reserved. Clinical Utility of Skin Biopsy in Differentiating between Parkinson’s Disease and Multiple System Atrophy Mon, 06 Apr 2015 07:56:35 +0000 Background. It is often difficult to differentiate Parkinson’s disease (PD) from multiple system atrophy (MSA), especially in their early stages. Objectives. To examine the clinical utility of histopathological analysis of biopsied skin from the chest wall and/or leg in differentiating between the two diseases. Methods. Skin biopsies from the lower leg and/or anterior chest wall were obtained from 38 patients with idiopathic PD (26 treated with levodopa and 12 levodopa-naïve) and 13 age-matched patients with MSA. We sought aggregates of phosphorylated α-synuclein on cutaneous nerve fibers using double fluorescence immunohistochemistry and confocal microscopy and measured intraepidermal nerve fiber density (IENFD). Results. Phosphorylated α-synuclein aggregates were identified on cutaneous nerves in two patients with PD (5.3%) but in none of the patients with MSA, and IENFD was significantly lower in patients with PD when compared to those with MSA. There was no difference in IENFD between levodopa-treated and levodopa-naïve patients with PD. Conclusions. Our findings suggest that an assessment of IENFD in biopsied skin could be a useful means of differentiating between PD and MSA but that detection of α-synuclein aggregates on cutaneous nerves in the distal sites of the body is insufficiently sensitive. Rie Haga, Kazuhiro Sugimoto, Haruo Nishijima, Yasuo Miki, Chieko Suzuki, Koichi Wakabayashi, Masayuki Baba, Soroku Yagihashi, and Masahiko Tomiyama Copyright © 2015 Rie Haga et al. All rights reserved. Iron Accumulation Is Not Homogenous among Patients with Parkinson’s Disease Sun, 05 Apr 2015 12:44:31 +0000 Background. Iron is considered to lead to neurodegeneration and has been hypothesized as a possible cause of Parkinson’s disease (PD). Susceptibility-weighted imaging (SWI) is a powerful tool to measure phase related iron content of brain. Methods. Twelve de novo patients with PD were recruited from the Movement Disorders Clinic, Department of Neurology, Loma Linda University. Twelve age- and sex-matched non-PD subjects were recruited from neurology clinic as controls. Using SWI, the phase related iron content was estimated from different brain regions of interest (ROIs). Results. There was a trend between increasing age and iron accumulation in the globus pallidus and putamen in all subjects. Iron accumulation was not significant in different ROIs in PD patients compared to controls after adjustment for age. Our data revealed heterogeneity of phase values in different brain ROIs among all subjects with an exaggerated trend at SN in PD patients. Conclusions. Our data suggest a nonhomogeneous pattern of iron accumulation in different brain regions among PD patients. Further studies are needed to explore whether this may correlate to the progression of PD. To our knowledge, this is the first study demonstrating the heterogeneity of iron accumulation in the brain, among patients with PD. Khashayar Dashtipour, Manju Liu, Camellia Kani, Pejman Dalaie, Andre Obenaus, Daniel Simmons, Nicole M. Gatto, and Mehran Zarifi Copyright © 2015 Khashayar Dashtipour et al. All rights reserved. Early Postural Changes in Individuals with Idiopathic Parkinson’s Disease Wed, 01 Apr 2015 14:14:38 +0000 Background and Objectives. Postural changes are frequent and disabling complications of Parkinson’s disease (PD). Many contributing factors have been evident either related to disease pathology or to adaptive changes. This study aimed at studying the postural changes in subjects with Parkinson’s disease and its relation to duration of illness and disease severity. Methods. Eighteen patients with PD and 18 healthy matched volunteers represented the sample of the study. The patients were at stage 1 or 1.5 according to the Modified Hoehn and Yahr Staging with duration of illness between 18 and 36 months. Three-dimensional analysis of the back surface was conducted to explore the postural changes in the sagittal and frontal planes in both the patients and the healthy subjects. Results. Kyphotic angle, lordotic angle, fleche cervicale, fleche lombaire, scoliotic angle, and associated vertebral rotation and pelvic obliquity were significantly increased in patients with PD compared to the healthy subjects (). There was no association between the measured postural changes and duration of illness as well as the severity of the IPD (). Conclusion. Postural changes start in the early stages of idiopathic PD and they have no relationship to the duration of illness and disease severity. Mohamed Elsayed Khallaf and Eman Elsayed Fayed Copyright © 2015 Mohamed Elsayed Khallaf and Eman Elsayed Fayed. All rights reserved. Cognitive Reserve in Parkinson’s Disease: The Effects of Welsh-English Bilingualism on Executive Function Wed, 01 Apr 2015 13:58:15 +0000 Objective. Bilingualism has been shown to benefit executive function (EF) and delay the onset of Alzheimer’s disease. This study aims at examining whether a bilingual advantage applies to EF in Parkinson’s disease (PD). Method. In a cross-sectional outpatient cohort of monolingual English () and bilingual Welsh/English () speakers with PD we evaluated the effects of bilingualism compared with monolingualism on performance on EF tasks. In bilinguals we also assessed the effects of the degree of daily usage of each language and the degree of bilingualism. Results. Monolinguals showed an advantage in performance of language tests. There were no differences in performance of EF tests in monolinguals and bilinguals. Those who used Welsh less in daily life had better performance on one test of English vocabulary. The degree of bilingualism correlated with one test of nonverbal reasoning and one of working memory but with no other tests of EF. Discussion. The reasons why the expected benefit in EF in Welsh-English bilinguals with PD was not found require further study. Future studies in PD should include other language pairs, analysis of the effects of the degree of bilingualism, and longitudinal analysis of cognitive decline or dementia together with structural or functional neuroimaging. John V. Hindle, Pamela A. Martin-Forbes, Alexandra J. M. Bastable, Kirstie L. Pye, Anthony Martyr, Christopher J. Whitaker, Fergus I. M. Craik, Ellen Bialystok, Enlli M. Thomas, Virginia C. Mueller Gathercole, and Linda Clare Copyright © 2015 John V. Hindle et al. All rights reserved. Mitochondrial Dysfunction and -Synuclein Synaptic Pathology in Parkinson’s Disease: Who’s on First? Tue, 31 Mar 2015 08:52:55 +0000 Parkinson’s disease (PD) is the most common neurodegenerative movement disorder. Its characteristic neuropathological features encompass the loss of dopaminergic neurons of the nigrostriatal system and the presence of Lewy bodies and Lewy neurites. These are intraneuronal and intraneuritic proteinaceous insoluble aggregates whose main constituent is the synaptic protein α-synuclein. Compelling lines of evidence indicate that mitochondrial dysfunction and α-synuclein synaptic deposition may play a primary role in the onset of this disorder. However, it is not yet clear which of these events may come first in the sequel of processes leading to neurodegeneration. Here, we reviewed data supporting either that α-synuclein synaptic deposition precedes and indirectly triggers mitochondrial damage or that mitochondrial deficits lead to neuronal dysfunction and α-synuclein synaptic accumulation. The present overview shows that it is still difficult to establish the exact temporal sequence and contribution of these events to PD. Michela Zaltieri, Francesca Longhena, Marina Pizzi, Cristina Missale, PierFranco Spano, and Arianna Bellucci Copyright © 2015 Michela Zaltieri et al. All rights reserved. Progesterone Exerts a Neuromodulatory Effect on Turning Behavior of Hemiparkinsonian Male Rats: Expression of 3α-Hydroxysteroid Oxidoreductase and Allopregnanolone as Suggestive of Receptors Involvement Tue, 31 Mar 2015 08:39:53 +0000 There is a growing amount of evidence for a neuroprotective role of progesterone and its neuroactive metabolite, allopregnanolone, in animal models of neurodegenerative diseases. By using a model of hemiparkinsonism in male rats, injection of the neurotoxic 6-OHDA in left striatum, we studied progesterone’s effects on rotational behavior induced by amphetamine or apomorphine. Also, in order to find potential explanatory mechanisms, we studied expression and activity of nigrostriatal 3α-hydroxysteroid oxidoreductase, the enzyme that catalyzes progesterone to its active metabolite allopregnanolone. Coherently, we tested allopregnanolone for a possible neuromodulatory effect on rotational behavior. Also, since allopregnanolone is known as a modulator, we finally examined the action of antagonist bicuculline. We found that progesterone, in addition to an apparent neuroprotective effect, also increased ipsilateral expression and activity of 3α-hydroxysteroid oxidoreductase. It was interesting to note that ipsilateral administration of allopregnanolone reversed a clear sign of motor neurodegeneration, that is, contralateral rotational behavior. A possible involvement modulated by allopregnanolone was shown by the blocking effect of bicuculline. Our results suggest that early administration of progesterone possibly activates genomic mechanisms that promote neuroprotection subchronically. This, in turn, could be partially mediated by fast, nongenomic, actions of allopregnanolone acting as an acute modulator of GABAergic transmission. Roberto Yunes, Sebastián Casas, Eliana Gaglio, and Ricardo Cabrera Copyright © 2015 Roberto Yunes et al. All rights reserved. The Neuroprotective Mechanism of Low-Frequency rTMS on Nigral Dopaminergic Neurons of Parkinson’s Disease Model Mice Wed, 25 Mar 2015 14:17:16 +0000 Background. Parkinson’s disease is a neurodegenerative disease in elder people, pathophysiologic basis of which is the severe deficiency of dopamine in the striatum. The purpose of the present study was to evaluate the neuroprotective effect of low-frequency rTMS on Parkinson’s disease in model mice. Methods. The effects of low-frequency rTMS on the motor function, cortex excitability, neurochemistry, and neurohistopathology of MPTP-induced Parkinson’s disease mice were investigated through behavioral detection, electrophysiologic technique, high performance liquid chromatography-electrochemical detection, immunohistochemical staining, and western blot. Results. Low-frequency rTMS could improve the motor coordination impairment of Parkinson’s disease mice: the resting motor threshold significantly decreased in the Parkinson’s disease mice; the degeneration of nigral dopaminergic neuron and the expression of tyrosine hydroxylase were significantly improved by low-frequency rTMS; moreover, the expressions of brain derived neurotrophic factor and glial cell line derived neurotrophic factor were also improved by low-frequency rTMS. Conclusions. Low-frequency rTMS had a neuroprotective effect on the nigral dopaminergic neuron which might be due to the improved expressions of brain derived neurotrophic factor and glial cell line-derived neurotrophic factor. The present study provided a theoretical basis for the application of low-frequency rTMS in the clinical treatment and recovery of Parkinson’s disease. Qiaoyun Dong, Yanyong Wang, Ping Gu, Rusheng Shao, Li Zhao, Xiqi Liu, Zhanqiang Wang, and Mingwei Wang Copyright © 2015 Qiaoyun Dong et al. All rights reserved. Monoamine Reuptake Inhibitors in Parkinson’s Disease Wed, 25 Feb 2015 10:36:55 +0000 The motor manifestations of Parkinson’s disease (PD) are secondary to a dopamine deficiency in the striatum. However, the degenerative process in PD is not limited to the dopaminergic system and also affects serotonergic and noradrenergic neurons. Because they can increase monoamine levels throughout the brain, monoamine reuptake inhibitors (MAUIs) represent potential therapeutic agents in PD. However, they are seldom used in clinical practice other than as antidepressants and wake-promoting agents. This review article summarises all of the available literature on use of 50 MAUIs in PD. The compounds are divided according to their relative potency for each of the monoamine transporters. Despite wide discrepancy in the methodology of the studies reviewed, the following conclusions can be drawn: (1) selective serotonin transporter (SERT), selective noradrenaline transporter (NET), and dual SERT/NET inhibitors are effective against PD depression; (2) selective dopamine transporter (DAT) and dual DAT/NET inhibitors exert an anti-Parkinsonian effect when administered as monotherapy but do not enhance the anti-Parkinsonian actions of L-3,4-dihydroxyphenylalanine (L-DOPA); (3) dual DAT/SERT inhibitors might enhance the anti-Parkinsonian actions of L-DOPA without worsening dyskinesia; (4) triple DAT/NET/SERT inhibitors might exert an anti-Parkinsonian action as monotherapy and might enhance the anti-Parkinsonian effects of L-DOPA, though at the expense of worsening dyskinesia. Philippe Huot, Susan H. Fox, and Jonathan M. Brotchie Copyright © 2015 Philippe Huot et al. All rights reserved. The Effects of Uric Acid, Serum Vitamin D3, and Their Interaction on Parkinson’s Disease Severity Tue, 24 Feb 2015 12:42:18 +0000 Objectives. In current study, the relationships between serum vitamin D3 levels and serum UA concentrations as well as their interaction with severity of PD were evaluated in a sample of Iranian PD patients. Method. In a cross sectional study at the one of the main referral hospitals in central region of Iran, during September to November 2011, 112 patients were recruited. Severity of PD was evaluated sing H&R stages and UPDRS. Results. The Spearman rank correlation coefficient suggests the negative significant association between serum vitamin D3 and UPDRS in patients aged >62 (, ). No statistically significant association was observed between the UA levels and severity of PD (represented by H&Y categories) in different levels of serum vitamin D3 not only in total sample but also in separate age and sex groups. The linear regression coefficients suggested positive association between UA and serum vitamin D3 with UPDRSIII scores while negative relationship between UA and serum vitamin D3 interaction with UPDRSIII; however it was only statistically significant in age group ≤62 (). Conclusion. Our study revealed a negative correlation between interaction of serum vitamin D3 and UA with severity of PD; other studies are required to confirm our findings. Rokhsareh Meamar, Pooria Shaabani, Seyed Reza Tabibian, Mohammad Reza Aghaye Ghazvini, and Awat Feizi Copyright © 2015 Rokhsareh Meamar et al. All rights reserved. Transdermal Rotigotine Improves Sleep Fragmentation in Parkinson’s Disease: Results of the Multicenter, Prospective SLEEP-FRAM Study Sun, 22 Feb 2015 12:26:05 +0000 Sleep disturbances occur frequently in patients with Parkinson’s disease (PD). The aim of this study was to investigate the effects of rotigotine on sleep fluctuations in a sample of PD patients with self-reported complaints of nocturnal awakenings. This prospective, open-label, observational, and multicenter study enrolled consecutive outpatients with PD and administered rotigotine (mean dose 8.9 mg/day) for 3 months. The primary endpoint was the change from baseline in sleep fragmentation, assessed using the sleep maintenance subscale score of the Parkinson’s Disease Sleep Scale (PDSS). The newly designed Parkinson’s Disease Sleep Fragmentation Questionnaire (PD-SFQ) was used to measure other sleep parameters. A total of 62 patients were enrolled (mean age 70.2 years; 66% male). At 3 months, rotigotine significantly improved sleep fragmentation from baseline on the PDSS-2 sleep maintenance subscale (from to ; ). Rotigotine also significantly improved nocturnal motor symptoms , restless legs-like symptoms , and nocturia . Rotigotine significantly improved self-reported complaints of sleep fragmentation in PD patients and could be a useful treatment to improve this specific sleep problem in PD. However, these results are based on a small and clinically heterogeneous sample so they must be taken cautiously. Javier Pagonabarraga, Gerard Piñol, Adriana Cardozo, Pilar Sanz, Víctor Puente, Pilar Otermín, Inés Legarda, Tania Delgado, Carmen Serrano, Ernest Balaguer, María Aguirregomozcorta, Ramiro Álvarez, and Jaime J. Kulisevsky Copyright © 2015 Javier Pagonabarraga et al. All rights reserved. The Genetic Link between Parkinson’s Disease and the Kynurenine Pathway Is Still Missing Tue, 17 Feb 2015 13:52:15 +0000 Background. There is substantial evidence that the kynurenine pathway (KP) plays a role in the normal physiology of the brain and is involved in the pathology of neurodegenerative disorders such as Huntington’s disease and Parkinson’s disease (PD). Objective. We set out to investigate the potential roles in PD of single nucleotide polymorphisms (SNPs) from one of the key enzymes of the KP, kynurenine 3-monooxygenase (KMO). Methods. 105 unrelated, clinically definitive PD patients and 131 healthy controls were enrolled to investigate the possible effects of the different alleles of KMO. Fluorescently labeled TaqMan probes were used for allele discrimination. Results. None of the four investigated SNPs proved to be associated with PD or influenced the age at onset of the disease. Conclusions. The genetic link between the KP and PD is still missing. The investigated SNPs presumably do not appear to influence the function of KMO and probably do not contain binding sites for regulatory proteins of relevance in PD. This is the first study to assess the genetic background behind the biochemical alterations of the kynurenine pathway in PD, directing the attention to this previously unexamined field. Nóra Török, Rita Török, Zoltán Szolnoki, Ferenc Somogyvári, Péter Klivényi, and László Vécsei Copyright © 2015 Nóra Török et al. All rights reserved. Early Freezing of Gait: Atypical versus Typical Parkinson Disorders Sun, 15 Feb 2015 10:35:23 +0000 In 18 months, 850 patients were referred to Muhammad Ali Parkinson Center (MAPC). Among them, 810 patients had typical Parkinson disease (PD) and 212 had PD for ≤5 years. Among the 212 patients with early PD, 27 (12.7%) had freezing of gait (FOG). Forty of the 850 had atypical parkinsonism. Among these 40 patients, all of whom had symptoms for ≤5 years, 12 (30.0%) had FOG. FOG improved with levodopa in 21/27 patients with typical PD but did not improve in the 12 patients with atypical parkinsonism. FOG was associated with falls in both groups of patients. We believe that FOG unresponsive to levodopa in typical PD resembles FOG in atypical parkinsonism. We thus compared the 6 typical PD patients with FOG unresponsive to levodopa plus the 12 patients with atypical parkinsonism with the 21 patients with typical PD responsive to levodopa. We compared them by tests of locomotion and postural stability. Among the patients with FOG unresponsive to levodopa, postural stability was more impaired than locomotion. This finding leads us to believe that, in these patients, postural stability, not locomotion, is the principal problem underlying FOG. Abraham Lieberman, Aman Deep, Rohit Dhall, An Tran, and Ming-Jai Liu Copyright © 2015 Abraham Lieberman et al. All rights reserved. Salivary Acetylcholinesterase Activity Is Increased in Parkinson’s Disease: A Potential Marker of Parasympathetic Dysfunction Thu, 12 Feb 2015 08:48:39 +0000 Introduction. Decreased salivary flow and xerostomia are frequent findings in Parkinson’s disease (PD), possibly caused by alterations in the parasympathetic tonus. Here we explore salivary acetylcholinesterase (AChE) activity as a potential biomarker in PD. Methods. We measured salivary flow, AChE activity, and total protein concentration in 30 PD patients and 49 healthy controls. We also performed exploratory correlation analyses with disease duration, motor symptom severity, autonomic complaints, and other nonmotor symptoms. Results. PD patients displayed significantly decreased salivary flow rate, significantly increased salivary AChE activity, and total protein concentration. Importantly, the AChE activity/total protein ratio was significantly increased in PD patients, suggesting that increased AChE activity cannot be explained solely by upconcentration of saliva. The Unified PD Rating Scale (UPDRS) score displayed significant correlation with total salivary protein () and near-significant correlation with salivary flow (). Color vision test scores were also significantly correlated with AChE activity () and total protein levels (). Conclusion. Salivary AChE activity is increased in PD patients compared to healthy controls. Future studies are needed to elucidate whether this parameter reflects the extent of neuronal damage and parasympathetic denervation in the salivary glands of PD patients. Tatyana Fedorova, Cindy Soendersoe Knudsen, Kim Mouridsen, Ebba Nexo, and Per Borghammer Copyright © 2015 Tatyana Fedorova et al. All rights reserved. Remarkably Few Sputum Cultures from People with Parkinson’s Disease during Hospital In-Patient Admission Thu, 05 Feb 2015 09:19:17 +0000 Although respiratory tract infections can be a common complication in people with Parkinson’s disease (PD), there is little published data on the nature of such infections in this patient group. We wished to investigate whether sputum samples were being taken from PD patients in order to establish whether an infection was present and if so which bacteria were responsible for the infection. We recorded the number of positive sputum samples taken from admission to North Tyneside General Hospital in North-East England across a ten-year period from June 2001 to June 2011. Of 643 in-patient episodes involving people with PD, positive sputum samples were recorded for only 12 episodes (1.9%) in eight patients. All patients were in early stage disease. In all admissions to the NHS Trust running the hospital, there were 23,069 sputum cultures from 1,056,693 in-patient episodes (2.2%). Our findings may reflect the difficultly of expectorating in many people with PD, particularly in late-stage disease. Since people with PD are especially vulnerable to respiratory tract infections, clinicians need to ensure that, where possible, a sputum sample is obtained from people with PD when clinically indicated. Richard W. Walker, Joel English, Grace Tan, Annette Fisher, and William K. Gray Copyright © 2015 Richard W. Walker et al. All rights reserved. Changes of Retina Are Not Involved in the Genesis of Visual Hallucinations in Parkinson’s Disease Tue, 03 Feb 2015 07:00:03 +0000 Parkinson’s disease (PD) is characterized by motor and nonmotor symptoms. Nonmotor symptoms include primarily visual hallucinations (VH). The aim of our study was to establish whether patients with PD and visual hallucinations (PDH+) have structural changes of retina detected by an optical coherence tomography (OCT) in comparison with PD patients without visual hallucinations (PDH−). We examined 52 PD patients (18 with VH, 34 without VH) and 15 age and sex matched healthy controls. Retinal nerve fiber layer (RNFL) thickness and macular thickness and volume were assessed by OCT. Functional impairment of retina was assessed using 2.5% contrast sensitivity test. For OCT outcomes we analyzed 15 PDH+ and 15 PDH− subjects matched for age, gender, and PD duration. For contrast sensitivity we analyzed 8 pairs of patients matched for age, gender, and visual acuity. There was no significant difference in RNFL thickness and macular thickness and macular volume between 15 PDH+ and 15 PDH− subjects, and also between a group of 44 PD patients (both PDH+ and PDH−) and 15 age and gender matched healthy controls. No significant difference was found for 2.5% contrast sensitivity test values between PDH+ and PDH− subjects. Therefore we conclude that functional and structural changes in retina play no role in genesis of VH in PD. Aleš Kopal, Eva Mejzlíková, Jana Lízrová Preiningerová, David Brebera, Olga Ulmanová, Edvard Ehler, and Jan Roth Copyright © 2015 Aleš Kopal et al. All rights reserved. Effect of Exercise on Motor and Nonmotor Symptoms of Parkinson’s Disease Mon, 02 Feb 2015 12:35:26 +0000 Background. Novel rehabilitation strategies have demonstrated potential benefits for motor and non-motor symptoms of Parkinson’s disease (PD). Objective. To compare the effects of Lee Silverman Voice Therapy BIG (LSVT BIG therapy) versus a general exercise program (combined treadmill plus seated trunk and limb exercises) on motor and non-motor symptoms of PD. Methods. Eleven patients with early-mid stage PD participated in the prospective, double-blinded, randomized clinical trial. Both groups received 16 one-hour supervised training sessions over 4 weeks. Outcome measures included the Unified Parkinson’s Disease Rating Scale (UPDRS), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) and Modified Fatigue Impact Scale (MFIS). Five patients performed general exercise and six patients performed LSVT BIG therapy. Post-intervention evaluations were conducted at weeks 4, 12 and 24. Results. The combined cohort made improvements at all follow-up evaluations with statistical significance for UPDRS total and motor, BDI, and MFIS (). Conclusion. This study demonstrated positive effects of general exercise and LSVT BIG therapy on motor and non-motor symptoms of patients with PD. Our results suggest that general exercise may be as effective as LSVT BIG therapy on symptoms of PD for patients not able to readily access outpatient LSVT BIG therapy. Khashayar Dashtipour, Eric Johnson, Camellia Kani, Kayvan Kani, Ehsan Hadi, Mark Ghamsary, Shant Pezeshkian, and Jack J. Chen Copyright © 2015 Khashayar Dashtipour et al. All rights reserved. The Natural History of Depression in Parkinson’s Disease within 30-Month Follow-Up Sun, 01 Feb 2015 11:41:56 +0000 Depression is one of the most common and persistent nonmotor syndromes occurring in 35% of patients diagnosed with PD. However, little information is known about the longitudinal study of its natural history of depression in PD. In this study, we identified 110 patients who are diagnosed with idiopathic PD and recruited them for assessing information about their PD related motor and nonmotor symptoms and rating scales. A follow-up evaluation was performed in 103 patients 30 months later. About 66.7% depressed patients at baseline were still depressed at follow-up, and 24.4% had incident depression among subjects without depression at baseline. Greater decline on MMSE (), higher baseline UPDRS-II () score, change of UPDRS-II (), and female () were associated with the worsening of HDRS scores. Higher baseline HDRS score () and greater decline on MMSE () were related to the occurrence of depression. In conclusion, cognitive decline is a disease related factor of worsening and the occurrence of depression. Activities of Daily Living (ADL) symptoms in PD and female gender may be crucial factors of increasing depressive symptoms. Yuan-Yuan Xu, Sheng-Han Kuo, Zheng Liang, Hui Xu, Wu-Ruo Feng, Cui-Yu Yu, and Wei-Guo Liu Copyright © 2015 Yuan-Yuan Xu et al. All rights reserved. German Translation and Validation of the “Freezing of Gait Questionnaire” in Patients with Parkinson’s Disease Thu, 29 Jan 2015 08:02:51 +0000 Background. Freezing of Gait (FOG) is a disabling parkinsonian symptom. The Freezing of Gait Questionnaire (FOG-Q) reliably detects FOG in patients with Parkinson’s disease (PD). Objectives. The aim of this study was to develop a German translated version of the FOG-Q and to assess its validity. Methods. The translation was accomplished using forward-backward-translation. The construct validity of the FOG-Q was examined in twenty-seven German native speaking PD patients. Convergent validity was assessed by correlating the FOG-Q with the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) II-III, the Parkinson Disease Questionnaire 39 (PDQ-39), and the Timed Up and Go Test (TUG). Divergent validity was assessed by correlating the FOG-Q with the MDS-UPDRS I. The internal consistency was measured using Cronbach’s alpha (Cα). Results. A good internal structure of the FOG-Q was found (). Significant moderate correlations between the FOG-Q and the MDS-UPDRS item 2.13 (freezing) (, ) and between the FOG-Q and the PDQ-39 subscale mobility (, ) were found. The lack of correlation with the MDS-UPDRS I demonstrated good divergent validity. Conclusion. The German FOG-Q is a valid tool to assess FOG in German native speaking PD patients. Anina Vogler, Jorina Janssens, Thomas Nyffeler, Stephan Bohlhalter, and Tim Vanbellingen Copyright © 2015 Anina Vogler et al. All rights reserved. Personality Changes after Deep Brain Stimulation in Parkinson’s Disease Thu, 29 Jan 2015 07:06:03 +0000 Objectives. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a recognized therapy that improves motor symptoms in advanced Parkinson’s disease (PD). However, little is known about its impact on personality. To address this topic, we have assessed personality traits before and after STN-DBS in PD patients. Methods. Forty patients with advanced PD were assessed with the Temperament and Character Inventory (TCI): the Urgency, Premeditation, Perseverance, Sensation Seeking impulsive behaviour scale (UPPS), and the Neuroticism and Lie subscales of the Eysenck Personality Questionnaire (EPQ-N, EPQ-L) before surgery and after three months of STN-DBS. Collateral information obtained from the UPPS was also reported. Results. Despite improvement in motor function and reduction in dopaminergic dosage patients reported lower score on the TCI Persistence and Self-Transcendence scales, after three months of STN-DBS, compared to baseline (; ). Relatives reported significantly increased scores on the UPPS Lack of Premeditation scale at follow-up (). Conclusion. STN-DBS in PD patients is associated with personality changes in the direction of increased impulsivity. Uyen Pham, Anne-Kristin Solbakk, Inger-Marie Skogseid, Mathias Toft, Are Hugo Pripp, Ane Eidahl Konglund, Stein Andersson, Ira Ronit Haraldsen, Dag Aarsland, Espen Dietrichs, and Ulrik Fredrik Malt Copyright © 2015 Uyen Pham et al. 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.