Parkinson’s Disease The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . 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. Disorders of the Oral Cavity in Parkinson’s Disease and Parkinsonian Syndromes Thu, 15 Jan 2015 11:56:14 +0000 Awareness of nonmotor symptoms of Parkinson’s disease is growing during the last decade. Among these, oral cavity disorders are, although prevalent, often neglected by the patients, their caregivers, and physicians. Some of these disorders include increased prevalence of caries and periodontal disease, sialorrhea and drooling, xerostomia, orofacial pain, bruxism, and taste impairment. Though many of these disorders are not fully understood yet and relatively few controlled trials have been published regarding their treatment, physicians should be aware of the body of evidence that does exist on these topics. This paper reviews current knowledge regarding the epidemiology, pathophysiology, and treatment options of disorders of the oral cavity in Parkinson’s disease patients. Yair Zlotnik, Yacov Balash, Amos D. Korczyn, Nir Giladi, and Tanya Gurevich Copyright © 2015 Yair Zlotnik et al. All rights reserved. MRI Correlates of Parkinson’s Disease Progression: A Voxel Based Morphometry Study Tue, 06 Jan 2015 07:02:12 +0000 We investigated structural brain differences between a group of early-mild PD patients at different phases of the disease and healthy subjects using voxel-based morphometry (VBM). 20 mild PD patients compared to 15 healthy at baseline and after 2 years of follow-up. VBM is a fully automated technique, which allows the identification of regional differences in the gray matter enabling an objective analysis of the whole brain between groups of subjects. With respect to controls, PD patients exhibited decreased GM volumes in right putamen and right parietal cortex. After 2 years of disease, the same patients confirmed GM loss in the putamen and parietal cortex; a significant difference was also observed in the area of pedunculopontine nucleus (PPN) and in the mesencephalic locomotor region (MLR). PD is associated with brain morphological changes in cortical and subcortical structures. The first regions to be affected in PD seem to be the parietal cortex and the putamen. A third structure that undergoes atrophy is the part of the inferior-posterior midbrain, attributable to the PPN and MLR. Our findings provide new insight into the brain involvement in PD and could contribute to a better understanding of the sequence of events occurring in these patients. Valentina Fioravanti, Francesca Benuzzi, Luca Codeluppi, Sara Contardi, Francesco Cavallieri, Paolo Nichelli, and Franco Valzania Copyright © 2015 Valentina Fioravanti et al. All rights reserved. Altered Brain Activation in Early Drug-Naive Parkinson’s Disease during Heat Pain Stimuli: An fMRI Study Mon, 05 Jan 2015 14:20:13 +0000 Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by motor and nonmotor signs and symptoms. To date, many studies of PD have focused on its cardinal motor symptoms. To study the nonmotor signs of early PD, we investigated the reactions solicited by heat pain stimuli in early untreated PD patients without pain using fMRI. The activation patterns of contact heat stimuli (51°C) were assessed in 14 patients and 17 age- and sex-matched healthy controls. Patients with PD showed significant decreases in activation of the superior temporal gyrus (STG) and insula compared with controls. In addition, a significant relationship between activation of the insula and STG and the pain scores was observed in healthy controls but not in PD. This study provided further support that the insula and STG are important parts of the somatosensory circuitry recruited during the period of pain. The hypoactivity of the STG and insula in PD implied that functions including affective, cognitive, and sensory-discriminative processes, which are associated with the insula and STG, were disturbed. This finding supports the view that leaving early PD untreated could be tied directly to central nervous system dysfunction. Ying Tan, Juan Tan, Cheng Luo, Wenjuan Cui, Hui He, Yi Bin, Jiayan Deng, Rui Tan, Wenrong Tan, Tao Liu, Nanlin Zeng, Ruhui Xiao, Dezhong Yao, and Xiaoming Wang Copyright © 2015 Ying Tan et al. All rights reserved. Comparison of the Psychological Symptoms and Disease-Specific Quality of Life between Early- and Typical-Onset Parkinson’s Disease Patients Mon, 29 Dec 2014 09:57:50 +0000 The impact of Parkinson’s disease (PD) on psychological status and quality of life (QoL) may vary depending on age of disease onset. The aim of this study was to compare psychological symptoms and disease-specific QoL between early onset versus the rest of the PD patients. A total number of 140 PD patients with the mean current age of 61.3  yr were recruited in this study. PD patients with the onset age of ≤50 yr were defined as “early-onset” (EOPD) group , while the ones with >50 yr at the time of diagnosis were categorized as the “typical-onset” (TOPD) patients . Different questionnaires and scales were used for between-group comparisons including PDQ39, HADS (hospital anxiety and depression scale), FSS (fatigue severity scale), MNA (mininutritional assessment), and the UPDRS. Depression score was significantly higher in EOPD group (6.3 versus 4.5 , ). Among different domains of QoL, emotion score was also significantly higher in the EOPD group (32.3 versus 24.4 , ). Our findings showed more severe depression and more impaired emotional domain of QoL in early-onset PD patients. Depression and anxiety play an important role to worsen QoL among both EOPD and TOPD patients, while no interaction was observed in the efficacy of these two psychiatric symptoms and the onset age of PD patients. Seyed-Mohammad Fereshtehnejad, Hasti Hadizadeh, Farzaneh Farhadi, Gholam Ali Shahidi, Ahmad Delbari, and Johan Lökk Copyright © 2014 Seyed-Mohammad Fereshtehnejad et al. All rights reserved. Polysomnographic Features of Sleep Disturbances and REM Sleep Behavior Disorder in the Unilateral 6-OHDA Lesioned Hemiparkinsonian Rat Thu, 25 Dec 2014 06:14:42 +0000 Sleep pattern disruption, specifically REM sleep behavior disorder (RBD), is a major nonmotor cause of disability in PD. Understanding the pathophysiology of these sleep pattern disturbances is critical to find effective treatments. 24-hour polysomnography (PSG), the gold standard for sleep studies, has never been used to test sleep dysfunction in the standard 6-OHDA lesioned hemiparkinsonian (HP) rat PD model. In this study, we recorded 24-hour PSG from normal and HP rats. Recordings were scored into wake, rapid eye movement (REM), and non-REM (NREM). We then examined EEG to identify REM periods and EMG to check muscle activity during REM. Normal rats showed higher wakefulness (70–80%) during the dark phase and lower wakefulness (20%) during the light phase. HP rats showed 30–50% sleep in both phases, less modulation and synchronization to the light schedule , and more long run lengths of wakefulness . HP rats also had more REM epochs with muscle activity than control rats . Our findings that the sleep architecture in the HP rat resembles that of PD patients demonstrate the value of this model in studying the pathophysiological basis of PD sleep disturbances and preclinical therapeutics for PD related sleep disorders including RBD. Quynh Vo, Timothy P. Gilmour, Kala Venkiteswaran, Jidong Fang, and Thyagarajan Subramanian Copyright © 2014 Quynh Vo et al. All rights reserved. Measuring Hemoglobin Levels in the Optic Disc of Parkinson’s Disease Patients Using New Colorimetric Analysis Software Tue, 23 Dec 2014 06:31:50 +0000 Objective. To evaluate a new method of measuring hemoglobin (Hb) levels and quantifying the color changes in the optic nerve head of Parkinson’s disease (PD) patients. We also compared differences in retinal nerve fiber layer (RNFL) thicknesses obtained using spectral domain optical coherence tomography (OCT) device between PD group and healthy group. Methods. One hundred and fifty-five PD patients and 91 sex- and age-matched healthy subjects were included in this cross-sectional study. OCT examinations and one photograph of the optic disc were performed. The Laguna ONhE (“optic nerve hemoglobin”; Insoft SL, Tenerife, Spain) software was used to analyze the Hb level on the acquired optic disc photographs. Results. PD patients exhibited significantly reduced mean optic disc Hb percentages (57.56% in PD, 67.63% in healthy subjects; ) as well as reduced Hb in almost all analyzed sectors, with the largest differences detected in the inferior and nasal sectors. RNFL parameters were significantly reduced in PD patients compared with healthy subjects, especially in the inferior quadrant. Conclusions. Measurements of optic disc Hb levels obtained with the Laguna ONhE software had good ability to detect optic nerve color changes (more papillary paleness and consequently this could suggest optic atrophy and axonal loss) in PD patients. Maria Pilar Bambo, Elena Garcia-Martin, Maria Satue, Susana Perez-Olivan, Silvia Alayon, Marta Gonzalez-Hernandez, Vicente Polo, Jose Manuel Larrosa, and Manuel Gonzalez-De la Rosa Copyright © 2014 Maria Pilar Bambo et al. All rights reserved. Effect of Centella asiatica Leaf Extract on the Dietary Supplementation in Transgenic Drosophila Model of Parkinson’s Disease Thu, 27 Nov 2014 00:10:08 +0000 The role of Centella asiatica L. leaf extract was studied on the transgenic Drosophila model flies expressing normal human alpha synuclein (h-αS) in the neurons. The leaf extract was prepared in acetone and was subjected to GC-MS analysis. C. asiatica extract at final concentration of 0.25, 0.50, and 1.0 μL/mL was mixed with the diet and the flies were allowed feeding on it for 24 days. The effect of extract was studied on the climbing ability, activity pattern, lipid peroxidation, protein carbonyl content, glutathione content, and glutathione-S-transferase activity in the brains of transgenic Drosophila. The exposure of extract to PD model flies results in a significant delay in the loss of climbing ability and activity pattern and reduced the oxidative stress () in the brains of PD flies as compared to untreated PD flies. The results suggest that C. asiatica leaf extract is potent in reducing the PD symptoms in transgenic Drosophila model of Parkinson’s disease. Yasir Hasan Siddique, Falaq Naz, Smita Jyoti, Ambreen Fatima, Saba Khanam, Rahul, Fahad Ali, Syed Faiz Mujtaba, and Mohammad Faisal Copyright © 2014 Yasir Hasan Siddique et al. All rights reserved. Recurrent Falls in People with Parkinson’s Disease without Cognitive Impairment: Focusing on Modifiable Risk Factors Sun, 23 Nov 2014 08:03:21 +0000 Falls can be considered a disabling feature in Parkinson’s disease. We aimed to identify risk factors for falling, testing simultaneously the ability of disease-specific and balance-related measures. We evaluated 171 patients, collecting demographic and clinical data, including standardized assessments with the Unified Parkinson’s Disease Rating Scale (UPDRS), activities of daily living (ADL) and motor sections, modified Hoehn and Yahr Scale, Schwab and England, eight-item Parkinson’s Disease Questionnaire, Activities-specific Balance Confidence Scale, Falls Efficacy Scale-International (FES-I), Berg Balance Scale, Dynamic Gait Index, Functional Reach, and Timed Up and Go. ROC curves were constructed to determine the cutoff scores for all measures. Variables with entered a logistic regression model. The prevalence of recurrent falls was 30% (95% CI 24%–38%). In multivariate analysis, independent risk factors for recurrent falls were () levodopa equivalent dose (OR = 1.283 per 100 mg increase; 95% CI = 1.092–1.507), UPDRS-ADL > 16 points (OR = 10.0; 95% CI = 3.6–28.3), FES-I > 30 points (OR = 6.0; 95% CI = 1.6–22.6), and Berg ≤ 48 points (OR = 3.9; 95% CI = 1.2–12.7).We encourage the utilization of these modifiable risk factors in the screening of fall risk. Lorena R. S. Almeida, Guilherme T. Valença, Nádja N. Negreiros, Elen B. Pinto, and Jamary Oliveira-Filho Copyright © 2014 Lorena R. S. Almeida et al. All rights reserved. Parkinson’s Disease: Low-Dose Haloperidol Increases Dopamine Receptor Sensitivity and Clinical Response Thu, 20 Nov 2014 07:01:36 +0000 Background. It is known that ultra-low doses of haloperidol can cause dopamine supersensitivity of dopamine D2 receptors and related behaviour in animals. Objective. The objective was to determine whether a daily ultra-low dose of 40 micrograms of haloperidol could enhance the clinical action of levodopa in Parkinson’s disease patients. Method. While continuing their daily treatment with levodopa, 16 patients with Parkinson’s disease were followed weekly for six weeks. They received an add-on daily dose of 40 micrograms of haloperidol for the first two weeks only. The SPES/SCOPA scale (short scale for assessment of motor impairments and disabilities in Parkinson’s disease) was administered before treatment and weekly throughout the trial. Results. The results showed a mean decrease in SPES/SCOPA scores after one week of the add-on treatment. Conclusion. SCOPA scores decreased after the addition of low-dose haloperidol to the standard daily levodopa dose. This finding is consistent with an increase in sensitivity of dopamine D2 receptors induced by haloperidol. Such treatment for Parkinson’s disease may possibly permit the levodopa dose to be reduced and, thus, delay the onset of levodopa side effects. Craig J. Hudson, Philip Seeman, and Mary V. Seeman Copyright © 2014 Craig J. Hudson et al. All rights reserved. Is the MDS-UPDRS a Good Screening Tool for Detecting Sleep Problems and Daytime Sleepiness in Parkinson’s Disease? Mon, 17 Nov 2014 07:47:27 +0000 Movement Disorder Society-sponsored Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) has separate items for measuring sleep problems (item 1.7) and daytime sleepiness (1.8). The aim of our study was to evaluate the screening sensitivity and specificity of these items to the PD Sleep Scale 2nd version (PDSS-2) and Epworth Sleepiness Scale (ESS). In this nationwide, cross-sectional study 460 PD patients were enrolled. Spearman’s rank correlation coefficients were calculated between the individual items, domains, and the total score of PDSS-2 and item 1.7 of MDS-UPDRS. Similarly, the items and the total score of ESS were contrasted to item 1.8 of MDS-UPDRS. After developing generalized ordinal logistic regression models, the transformed and observed scores were compared by Lin’s Concordance Correlation Coefficient. Only item 3 difficulties staying asleep and the “disturbed sleep” domain of PDSS-2 showed high correlation with “sleep problems” item 1.7 of the MDS-UPDRS. Total score of PDSS-2 had moderate correlation with this MDS-UPRDS item. The total score of ESS showed the strongest, but still moderate, correlation with “daytime sleepiness” item 1.8 of MDS-UPDRS. As intended, the MDS-UPDRS serves as an effective screening tool for both sleep problems and daytime sleepiness and identifies subjects whose disabilities need further investigation. Krisztina Horváth, Zsuzsanna Aschermann, Péter Ács, Edit Bosnyák, Gabriella Deli, Endre Pál, József Janszky, Béla Faludi, Ildikó Késmárki, Sámuel Komoly, Magdolna Bokor, Eszter Rigó, Júlia Lajtos, Péter Klivényi, György Dibó, László Vécsei, Annamária Takáts, Adrián Tóth, Piroska Imre, Ferenc Nagy, Mihály Herceg, Anita Kamondi, Eszter Hidasi, and Norbert Kovács Copyright © 2014 Krisztina Horváth et al. All rights reserved. Oleanolic Acid Enhances the Beneficial Effects of Preconditioning on PC12 Cells Thu, 13 Nov 2014 07:10:28 +0000 Preconditioning triggers endogenous protection against subsequent exposure to higher concentrations of a neurotoxin. In this study, we investigated whether exposure to oleanolic acid (OA) enhances the protective effects of preconditioning on PC12 cells exposed to 6-hydroxydopamine (6-OHDA). A concentration response curve was constructed using 6-OHDA (50, 150, 300, and 600 μM). The experiment consisted of 6 groups: untreated, OA only, Group 1: cells treated with 6-OHDA (50 μM) for 1 hour, Group 2: cells treated with 6-OHDA (150 μM) for 1 hour, Group 3: cells treated with 6-OHDA (50 μM) for 30 minutes followed 6 hours later by treatment with 6-OHDA (150 μM) for 30 minutes, and Group 4: cells treated as in group 3 but also received OA immediately after the second 6-OHDA treatment. Cell viability and apoptotic ratio were assessed using the MTT and Annexin V staining tests, respectively. In preconditioned cells, we found that cell viability remained high following exposure to 6-OHDA (150 μM). OA treatment enhanced the protective effects of preconditioning. Similarly, with the annexin V apoptosis test, preconditioning protected the cell and this was enhanced by OA. Therefore, preexposure of PC12 cells to low 6-OHDA concentration can protect against subsequent toxic insults of 6-OHDA and OA enhances this protection. Babongile C. Ndlovu, Willie M. U. Daniels, and Musa V. Mabandla Copyright © 2014 Babongile C. Ndlovu et al. All rights reserved. Validation of the Persian Translation of the Swallowing Disturbance Questionnaire in Parkinson’s Disease Patients Mon, 27 Oct 2014 08:45:05 +0000 Dysphagia, as a common finding in Parkinson’s disease (PD) patients, was estimated to be present in 80–95% of this population during different stages of the disease. The Swallowing Disturbance Questionnaire (SDQ) was created as a self-rated dysphagia screening tool in PD. According to the guidelines for cross-cultural adaptation, Persian version of this questionnaire (SDQ-P) was developed. 59 Persian patients (39 men and 20 women) participated in the study. They responded to the SDQ-P and underwent videofluoroscopic swallowing study (VFSS). Aspiration during VFSS was compared with questionnaire results for each individual. Cronbach’s alpha coefficient for the questionnaire was 0.86 and based on SDQ-P 15 patients (25.4%) were dysphagic, while 10 patients (16.9%) showed aspiration during VFSS. SDQ-P sensitivity and specificity in predicting aspiration were 96.7 and 91.2%; therefore, the SDQ-P could be a prognostic tool for aspiration. The positive predictive value (PPV), the negative predictive value (NPV), and the pre- and posttest probabilities of aspiration were 0.67, 1, 16.9%, and 66.7%, respectively. In summary, this study demonstrated the reliability and also the feasibility of SDQ-P for screening of aspiration in Iranian patients with PD. Further evaluation of SDQ-P in larger subject population would be suggested. Ali Rajaei, S. Abolfazl Azargoon, Mohammad Hussein Nilforoush, Ebrahim Barzegar Bafrooei, Fereshteh Ashtari, and Ahmad Chitsaz Copyright © 2014 Ali Rajaei et al. All rights reserved.