http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2013 , Hindawi Publishing Corporation . All rights reserved. Wed, 08 May 2013 09:40:41 +0000 http://www.hindawi.com/journals/pd/2013/751925/ Background. Parkinson disease (PD) is characterized by hypometric movements resulting from loss of dopaminergic neurons in the substantia nigra. PD leads to decreased activation of the supplementary motor area (SMA); the net result of these changes is a poverty of movement. The present study determined the impact of 5 Hz repetitive transcranial magnetic stimulation (rTMS) over the SMA on a fine motor movement, handwriting (writing cursive “l”s), and on cortical excitability, in individuals with PD. Methods. In a cross-over design, ten individuals with PD were randomized to receive either 5 Hz or control stimulation over the SMA. Immediately following brain stimulation right handed writing was assessed. Results. 5 Hz stimulation increased vertical size of handwriting and diminished axial pressure. In addition, 5 Hz rTMS significantly decreased the threshold for excitability in the primary motor cortex. Conclusions. These data suggest that in the short term 5 Hz rTMS benefits functional fine motor task performance, perhaps by altering cortical excitability across a network of brain regions. Further, these data may provide the foundation for a larger investigation of the effects of noninvasive brain stimulation over the SMA in individuals with PD. Bubblepreet K. Randhawa, Becky G. Farley, and Lara A. Boyd Copyright © 2013 Bubblepreet Kaur Randhawa et al. All rights reserved. Tue, 30 Apr 2013 11:25:20 +0000 http://www.hindawi.com/journals/pd/2013/572134/ Background. It is widely believed that exercise improves mobility in people with Parkinson’s disease (PD). However, it is difficult to determine whether a specific type of exercise is the most effective. The purpose of this study was to determine which outcome measures were sensitive to exercise intervention and to explore the effects of two different exercise programs for improving mobility in patients with PD. Methods. Participants were randomized into either the Agility Boot Camp (ABC) or treadmill training; 4x/week for 4 weeks. Outcome measures were grouped by the International Classification of Function/Disability (ICF). To determine the responsiveness to exercise, we calculated the standardized response means. -tests were used to compare the relative benefits of each exercise program. Results. Four of five variables at the structure/function level changed after exercise: turn duration (), stride velocity (), peak arm speed (), and horizontal trunk ROM during gait (). Most measures improved similarly for both interventions. The only variable that detected a difference between groups was postural sway in ABC group (; ). Conclusion. Outcome measures at ICF body structure/function level were most effective at detecting change after exercise and revealing differences in improvement between interventions. L. A. King, A. Salarian, M. Mancini, K. C. Priest, J. Nutt, A. Serdar, J. Wilhelm, J. Schlimgen, M. Smith, and F. B. Horak Copyright © 2013 L. A. King et al. All rights reserved. Tue, 26 Mar 2013 08:54:34 +0000 http://www.hindawi.com/journals/pd/2013/710839/ Objectives. To explore whether aspects of housing and health among very old people with self-reported Parkinson’s disease (PD) differ from matched controls. Methods. Data from the ENABLE-AGE Survey Study were used to identify people with self-reported PD () and three matched controls/individual (). The matching criteria were age (mean = 82 years), sex, country, and type of housing. The analyses targeted problems in activities of daily living, objective and perceived aspects of housing, for example, number of environmental barriers, accessibility (i.e., person-environment fit), and usability. Results. The number of physical environmental barriers did not differ () between the samples. The PD sample had more () accessibility problems than controls and perceived their homes as less () usable in relation to activities. They were less independent and had more functional limitations (median 5 versus 2; ), and 70% experienced loss of stamina or poor balance. Conclusions. Due to the fact that they have more functional limitations than very old people in general, those with self-reported PD live in housing with more accessibility problems. This explorative study has implications for rehabilitation as well as societal planning, but larger studies including people with a confirmed PD diagnosis are needed. Maria H. Nilsson, Maria Haak, and Susanne Iwarsson Copyright © 2013 Maria H. Nilsson et al. All rights reserved. Tue, 05 Mar 2013 13:58:37 +0000 http://www.hindawi.com/journals/pd/2013/906274/ Most people with Parkinson’s disease (PD) fall and many experience recurrent falls. The aim of this review was to examine the scope of recurrent falls and to identify factors associated with recurrent fallers. A database search for journal articles which reported prospectively collected information concerning recurrent falls in people with PD identified 22 studies. In these studies, 60.5% (range 35 to 90%) of participants reported at least one fall, with 39% (range 18 to 65%) reporting recurrent falls. Recurrent fallers reported an average of 4.7 to 67.6 falls per person per year (overall average 20.8 falls). Factors associated with recurrent falls include: a positive fall history, increased disease severity and duration, increased motor impairment, treatment with dopamine agonists, increased levodopa dosage, cognitive impairment, fear of falling, freezing of gait, impaired mobility and reduced physical activity. The wide range in the frequency of recurrent falls experienced by people with PD suggests that it would be beneficial to classify recurrent fallers into sub-groups based on fall frequency. Given that there are several factors particularly associated with recurrent falls, fall management and prevention strategies specifically targeting recurrent fallers require urgent evaluation in order to inform clinical practice. Natalie E. Allen, Allison K. Schwarzel, and Colleen G. Canning Copyright © 2013 Natalie E. Allen et al. All rights reserved. Sun, 24 Feb 2013 08:06:04 +0000 http://www.hindawi.com/journals/pd/2013/704237/ Introduction. We know little about how environmental challenges beyond home exacerbate difficulty moving, leading to falls among people with Parkinson’s (PwP). Aims. To survey falls beyond home, identifying challenges amenable to behaviour change. Methods. We distributed 380 questionnaires to PwP in Southern England, asking participants to count and describe falls beyond home in the previous 12 months. Results. Among 255 responses, 136 PwP (diagnosed a median 8 years) reported falling beyond home. They described 249 falls in detail, commonly falling forward after tripping in streets. Single fallers (one fall in 12 months) commonly missed their footing, walking, or changing position and recovered to standing alone or with unfamiliar help. Repeat fallers (median falls, two) commonly felt shaken or embarrassed and sought medical advice. Very frequent fallers (falling at least monthly; median falls beyond home, six) commonly fell backward, in shops and after collapse but often recovered to standing alone. Conclusion. Even independently active PwP who do not fall at home may fall beyond home, often after tripping. Falling beyond home may result in psychological and/or physical trauma (embarrassment if observed by strangers and/or injury if falling backwards onto a hard surface). Prevention requires vigilance and preparedness: slowing down and concentrating on a single task might effectively prevent falling. Emma L. Stack and Helen C. Roberts Copyright © 2013 Emma L. Stack and Helen C. Roberts. All rights reserved. Sun, 17 Feb 2013 11:38:45 +0000 http://www.hindawi.com/journals/pd/2013/974964/ Background. Parkinson’s disease (PD) is a neurodegenerative condition with complex subtleties, making it challenging for physicians to fully inform their patients. Given that approximately 50% of Americans access the Internet for health information, the development of a multimedia, web-based application emphasizing targeted needs of people with Parkinson’s disease (PwP) has the potential to change patient’s lives. Objectives. To determine what information PwP perceive could enhance their quality of life. Methods. Group sessions utilizing nominal group technique (NGT) were conducted. Participants were asked “what information do you want to know about that would help you live well with PD?” Silent generation of ideas preceded discussion followed by anonymous ranking of items. A “summary score” (sum of rank × frequency) was calculated. Results. 36 individual items were collapsed into 9 categories. Coping with emotions, changing relationships, and social implications of PD were ranked as most important. Financial supports and skills for self-advocacy were also highly ranked. Conclusions. Qualitative research methodology was utilized to determine the unmet needs of PwP. Results of this survey will inform the development of a patient-oriented, online resource, the goal will be to provide information and strategies to improve symptom management, reduce disability and address all relevant concerns important to those affected by PD. Galit Kleiner-Fisman, Pearl Gryfe, and Gary Naglie Copyright © 2013 Galit Kleiner-Fisman et al. All rights reserved. Wed, 13 Feb 2013 09:22:15 +0000 http://www.hindawi.com/journals/pd/2013/362908/ Treatment options in advanced Parkinson’s disease (PD) include subcutaneous apomorphine, pallidal or subthalamic nucleus Deep Brain Stimulation (DBS), or levodopa/carbidopa intestinal gel (LCIG/Duodopa). In this study, we describe the outcome of 12 PD patients with PD related complications started on LCIG, with respect to their quality of life measured by a disease specific validated scale—the PDQ39, together with diaries recording time spent “On,” “Off,” “Dyskinetic,” or “Asleep.” At the time of latest follow up, improvements were observed in both the PDQ39 Summary index as well as diary reports of PD symptom control following introduction of LCIG, supporting its use in well selected patients. The use of a trial period of LCIG via naso-jejunal administration allows objective evaluation of improvement in PD symptom control in advance of the placement of the more invasive percutaneous jejunostomy procedure. The decision to embark on LCIG, apomorphine or DBS should be supported by input from centres with experience of all 3 approaches. Since LCIG is an expensive option, development of the most appropriate future commissioning of this therapy in the absence of Class 1 evidence requires careful scrutiny of the outcomes of its use in a broad range of published series. T. Foltynie, C. Magee, C. James, G. J. M. Webster, A. J. Lees, and P. Limousin Copyright © 2013 T. Foltynie et al. All rights reserved. Tue, 12 Feb 2013 09:38:17 +0000 http://www.hindawi.com/journals/pd/2013/436481/ Rosa Ana González-Polo, José Manuel Fuentes, Mireia Niso-Santano, and Lydia Álvarez-Erviti Copyright © 2013 Rosa Ana González-Polo et al. All rights reserved. Mon, 11 Feb 2013 15:44:41 +0000 http://www.hindawi.com/journals/pd/2013/742128/ The aim of this study is to investigate the frequency and clinical features of gastroesophageal reflex disease (GERD) in Parkinson’s disease (PD). Consecutively recruited PD patients and controls were questioned about heartburn and GERD with a questionnaire. In PD patients, disease duration and severity, quality of life, and nonmotor symptoms were also examined and then the clinical features of GERD were analyzed. A total of 102 patients and 49 controls were enrolled and 21 patients and 4 controls had heartburn, significantly frequent in PD. The prevalence rate of GERD was 26.5% in PD and the odds ratio was 4.05. Heartburn, bent forward flexion, and wearing-off phenomenon were frequent, and scores of UPDRS, total and part II, PD questionnaire-39, and nonmotor symptom scale were significantly higher in PD patients with GERD than without GERD. Multiple logistic regression analysis revealed statistical significance in UPDRS part II and nonmotor symptom scale. This study suggests that GERD is prevalent in PD. Deterioration of daily living activities and other nonmotor symptoms can imply the presence of GERD. Because clinical symptoms of GERD are usually treatable, the management can improve the patient’s quality of life. Increased attention should be given to detect GERD in PD. Tetsuya Maeda, Ken Nagata, Yuichi Satoh, Takashi Yamazaki, and Daiki Takano Copyright © 2013 Tetsuya Maeda et al. All rights reserved. Thu, 07 Feb 2013 08:12:26 +0000 http://www.hindawi.com/journals/pd/2013/308052/ Parkinson's disease (PD) is a neurodegenerative disorder predominantly affecting the elderly. The aetiology of the disease is not known, but age and environmental factors play an important role. Although more than a dozen gene mutations associated with familial forms of Parkinson's disease have been described, fewer than 10% of all cases can be explained by genetic abnormalities. The molecular basis of Parkinson's disease is the loss of dopamine in the basal ganglia (caudate/putamen) due to the degeneration of dopaminergic neurons in the substantia nigra, which leads to the motor impairment characteristic of the disease. Methamphetamine is the second most widely used illicit drug in the world. In rodents, methamphetamine exposure damages dopaminergic neurons in the substantia nigra, resulting in a significant loss of dopamine in the striatum. Biochemical and neuroimaging studies in human methamphetamine users have shown decreased levels of dopamine and dopamine transporter as well as prominent microglial activation in the striatum and other areas of the brain, changes similar to those observed in PD patients. Consistent with these similarities, recent epidemiological studies have shown that methamphetamine users are almost twice as likely as non-users to develop PD, despite the fact that methamphetamine abuse and PD have distinct symptomatic profiles. Noelia Granado, Sara Ares-Santos, and Rosario Moratalla Copyright © 2013 Noelia Granado et al. All rights reserved. Sun, 27 Jan 2013 13:23:06 +0000 http://www.hindawi.com/journals/pd/2013/258374/ Parkinsonian rigidity has been thought to be constant through a full range of joint angle. The aim of this study was to perform a detailed investigation of joint angle dependency of rigidity. We first measured muscle tone at the elbow joint in 20 healthy subjects and demonstrated that an angle of approximately 60° of flexion marks the division of two different angle-torque characteristics. Then, we measured muscle tone at the elbow joint in 24 Parkinson’s Disease (PD) patients and calculated elastic coefficients in flexion and extension in the ranges of 10°–60° (distal) and 60°–110° (proximal). Rigidity as represented by the elastic coefficient in the distal phase of elbow joint extension was best correlated with the UPDRS rigidity score (). A significant difference between the UPDRS rigidity score 0 group and 1 group was observed in the elastic coefficient in the distal phase of extension (), whereas no significant difference was observed in the proximal phase of extension and in each phase of flexion. Parkinsonian rigidity shows variable properties depending on the elbow joint angle, and it is clearly detected at the distal phase of elbow extension. Takuyuki Endo, Toshimitsu Hamasaki, Ryuhei Okuno, Masaru Yokoe, Harutoshi Fujimura, Kenzo Akazawa, and Saburo Sakoda Copyright © 2013 Takuyuki Endo et al. All rights reserved. Sun, 30 Dec 2012 18:11:45 +0000 http://www.hindawi.com/journals/pd/2012/205471/ Parkinson's disease (PD) has traditionally been characterized by its cardinal motor symptoms of bradykinesia, rigidity, resting tremor, and postural instability. However, PD is increasingly being recognized as a multidimensional disease associated with myriad nonmotor symptoms including autonomic dysfunction, mood disorders, cognitive impairment, pain, gastrointestinal disturbance, impaired olfaction, psychosis, and sleep disorders. Sleep disturbances, which include sleep fragmentation, daytime somnolence, sleep-disordered breathing, restless legs syndrome (RLS), nightmares, and rapid eye movement (REM) sleep behavior disorder (RBD), are estimated to occur in 60% to 98% of patients with PD. For years nonmotor symptoms received little attention from clinicians and researchers, but now these symptoms are known to be significant predictors of morbidity in determining quality of life, costs of disease, and rates of institutionalization. A discussion of the clinical aspects, pathophysiology, evaluation techniques, and treatment options for the sleep disorders that are encountered with PD is presented. Todd J. Swick Copyright © 2012 Todd J. Swick. All rights reserved. Sat, 29 Dec 2012 15:35:55 +0000 http://www.hindawi.com/journals/pd/2012/671261/ Gait impairments are prevalent among people with Parkinson’s disease (PD). Instructions to focus on walking can improve walking in PD, but the use of such a cognitive strategy may be limited under dual-task walking conditions, when walking is performed simultaneously with concurrent cognitive or motor tasks. This study examined how dual-task performance of walking and a concurrent cognitive task was affected by instructions in people with PD compared to healthy young and older individuals. Dual-task walking and cognitive task performance was characterized under two sets of instructions as follows: (1) focus on walking and (2) focus on the cognitive task. People with PD and healthy adults walked faster when instructed to focus on walking. However, when focused on walking, people with PD and young adults demonstrated declines in the cognitive task. This suggests that dual-task performance is flexible and can be modified by instructions in people with PD, but walking improvements may come at a cost to cognitive task performance. The ability to modify dual-task performance in response to instructions or other task and environmental factors is critical to mobility in daily life. Future research should continue to examine factors that influence dual-task performance among people with PD. Valerie E. Kelly, Alexis J. Eusterbrock, and Anne Shumway-Cook Copyright © 2012 Valerie E. Kelly et al. All rights reserved. Sun, 23 Dec 2012 15:26:59 +0000 http://www.hindawi.com/journals/pd/2012/767105/ Sleep disorders are common in Parkinson's disease (PD) and seem to be strongly associated with depression. It has been suggested that sleep disorders as well as depression are caused by a disturbed circadian rhythm. Indeed, PD patients are prone to misalignment of their circadian rhythm due to various factors, and many patients with PD display a phase advance of their circadian rhythm. Current treatment options for sleep disorders and depression in patients with PD are limited and can have serious side effects; alternative treatments are therefore badly needed. Bright light therapy (BLT) restores circadian rhythmicity effectively in mood- and sleep-disturbed patients without PD. The few studies that focused on the efficacy of BLT in patients with PD demonstrated a positive effect of BLT not only on sleep and mood but also on motor function. More research on the neurobiology and efficacy of BLT in PD is warranted. Sonja Rutten, Chris Vriend, Odile A. van den Heuvel, Jan H. Smit, Henk W. Berendse, and Ysbrand D. van der Werf Copyright © 2012 Sonja Rutten et al. All rights reserved. Thu, 20 Dec 2012 11:35:46 +0000 http://www.hindawi.com/journals/pd/2012/190901/ The quality of life (QoL) of informal caregivers can be adversely affected by a number of factors. This issue, however, has not been well explored for carers of people with Parkinson's (PwP), with research largely restricted to the assessment of caregiver burden and caregiver strain. This study aims to determine the main influences on carer QoL in this population and consider results in the context of current clinical guidelines for the management of Parkinson's disease (PD). Carers completed the newly validated PDQ-Carer, and PwP completed the PDQ-39. The sample comprised 238 carers (mean age 68.20 years) and 238 PwP (mean age 71.64). Results suggest multiple influences on caregiver QoL. These include carer age, gender, health status, and duration of the caregiving role. PwP levels of mobility and cognitive impairment are also significant influences on carer QoL. Not only should practitioners and service providers be particularly aware of the heightened impact of PD on carers over time and as PwP symptoms deteriorate, but this should also be reflected in clinical guidelines for the management of PD. D. Morley, S. Dummett, M. Peters, L. Kelly, P. Hewitson, J. Dawson, R. Fitzpatrick, and C. Jenkinson Copyright © 2012 D. Morley et al. All rights reserved. Tue, 18 Dec 2012 17:50:28 +0000 http://www.hindawi.com/journals/pd/2012/541908/ Parkinson's disease (PD) is a progressive neurodegenerative disorder related to the loss or absence of dopaminergic neurons in the brain. These deficits result in slowness of movement, tremor, rigidity, and dysfunction of behaviour. These symptoms negatively influence the patient’s capability to carry out the daily oral hygiene manoeuvres. The aim of this work is to record the oral health condition of PD patients evaluated at the IRCSS Bonino-Puleio in Messina. The oral health of 45 consecutive PD patients (study group) with neurologic diagnosis based on United Kingdom Brain Bank Criteria has been compared with that of another 45 no PD patients of the same age (control group). The evaluation of the general oral condition was recorded underlining tooth loss, active periodontal disease, and presence of untreated caries. The frequency of untreated caries, periodontal diseases, and missing teeth of the study group was significantly higher than in control group. Based on the data results, clinicians should direct high attention to the oral hygiene of patients with PD, above all at the early stages of the caries or periodontal disease, in order to prevent serious evolution of those pathologic dental conditions that may finally result in the tooth extraction event. Marco Cicciù, Giacomo Risitano, Giuseppe Lo Giudice, and Ennio Bramanti Copyright © 2012 Marco Cicciù et al. All rights reserved. Thu, 13 Dec 2012 11:05:18 +0000 http://www.hindawi.com/journals/pd/2012/639080/ Anna Rosa Carta, Andrea Giuffrida, and Gilberto Fisone Copyright © 2012 Anna Rosa Carta et al. All rights reserved. Mon, 03 Dec 2012 09:47:18 +0000 http://www.hindawi.com/journals/pd/2012/324521/ Parkinson's disease is a debilitating neurodegenerative disorder, and its molecular etiopathogenesis remains poorly understood. The discovery of monogenic forms has significantly advanced our understanding of the molecular mechanisms underlying PD, as it allows generation of cellular and animal models carrying the mutant gene to define pathological pathways. Mutations in leucine-rich repeat kinase 2 (LRRK2) cause dominantly inherited PD, and variations increase risk, indicating that LRRK2 is an important player in both genetic and sporadic forms of the disease. G2019S, the most prominent pathogenic mutation, maps to the kinase domain and enhances enzymatic activity of LRRK2, which in turn seems to correlate with cytotoxicity. Since kinases are druggable targets, this has raised great hopes that disease-modifying therapies may be developed around modifying LRRK2 enzymatic activity. Apart from cytotoxicity, changes in autophagy have been consistently reported in the context of G2019S mutant LRRK2. Here, we will discuss current knowledge about mechanism(s) by which mutant LRRK2 may regulate autophagy, which highlights additional putative therapeutic targets. Patricia Gómez-Suaga, Elena Fdez, Marian Blanca Ramírez, and Sabine Hilfiker Copyright © 2012 Patricia Gómez-Suaga et al. All rights reserved. Wed, 21 Nov 2012 11:45:58 +0000 http://www.hindawi.com/journals/pd/2012/850596/ Deep brain stimulation (DBS) has been reported to be successful in relieving the core motor symptoms of Parkinson's disease (PD) and motor fluctuations in the more advanced stages of the disease. However, data on the effects of DBS on speech performance are inconsistent. While there are some series of patients documenting that speech function was relatively unaffected by DBS of the nucleus subthalamicus (STN), other investigators reported on improvements of distinct parameters of oral control and voice. Though, these ameliorations of single speech modalities were not always accompanied by an improvement of overall speech intelligibility. On the other hand, there are also indications for an induction of dysarthria as an adverse effect of STN-DBS occurring at least in some patients with PD. Since a deterioration of speech function has more often been observed under high stimulation amplitudes, this phenomenon has been ascribed to a spread of current-to-adjacent pathways which might also be the reason for the sporadic observation of an onset of dysarthria under DBS of other basal ganglia targets (e.g., globus pallidus internus/GPi or thalamus/Vim). The aim of this paper is to review and evaluate reports in the literature on the effects of DBS on speech function in PD. Sabine Skodda Copyright © 2012 Sabine Skodda. All rights reserved. Wed, 07 Nov 2012 09:28:11 +0000 http://www.hindawi.com/journals/pd/2012/860923/ Parkinson’s disease (PD) has become a major health problem affecting 1.5% of the world’s population over 65 years of age. As life expectancy has increased so has the occurrence of PD. The primary direct consequence of this disease is the loss of dopaminergic (DA) neurons in the substantia nigra and striatum. As the intensity of motor dysfunction increases, the symptomatic triad of bradykinesia, tremors-at-rest, and rigidity occur. Progressive neurodegeneration may also impact non-DA neurotransmitter systems including cholinergic, noradrenergic, and serotonergic, often leading to the development of depression, sleep disturbances, dementia, and autonomic nervous system failure. L-DOPA is the most efficacious oral delivery treatment for controlling motor symptoms; however, this approach is ineffective regarding nonmotor symptoms. New treatment strategies are needed designed to provide neuroprotection and encourage neurogenesis and synaptogenesis to slow or reverse this disease process. The hepatocyte growth factor (HGF)/c-Met receptor system is a member of the growth factor family and has been shown to protect against degeneration of DA neurons in animal models. Recently, small angiotensin-based blood-brain barrier penetrant mimetics have been developed that activate this HGF/c-Met system. These compounds may offer a new and novel approach to the treatment of Parkinson’s disease. John W. Wright and Joseph W. Harding Copyright © 2012 John W. Wright and Joseph W. Harding. All rights reserved. Wed, 31 Oct 2012 08:56:19 +0000 http://www.hindawi.com/journals/pd/2012/923493/ Introduction. We aimed to determine whether gait velocity is as useful as a balance test, a self-report measure of freezing of gait (FOG), and/or a measure of motor symptom severity for predicting falls among people with Parkinson Disease (PD). Methods. Fifty-six individuals with idiopathic PD completed a baseline assessment consisting of these measures: (1) MDS-UPDRS III, (2) Mini-BESTest, (3) gait velocity (forward, backward, dual task, and fast), and (4) FOGQ. Retrospective fall history was collected at baseline and six months later. Participants were considered fallers if they had two or more falls in the surveillance period. Ability of the tests to discriminate between fallers and nonfallers was determined using ROC curves followed by pairwise statistical noninferiority comparisons () of the area under the ROC curve (AUC) for each test. Results. At six months, 22% () of the sample were fallers. Fallers differed significantly from nonfallers on the MDS-UPDRS III, Mini-BESTest, backward gait velocity, and FOGQ. The Mini-BESTest had the highest AUC and was superior to all gait velocity measures at identifying fallers. Conclusion. A single measure of gait velocity, even in a challenging condition, may not be as effective as the Mini-BESTest in identifying fallers among people with PD. Ryan P. Duncan and Gammon M. Earhart Copyright © 2012 Ryan P. Duncan and Gammon M. Earhart. All rights reserved. Mon, 22 Oct 2012 08:34:39 +0000 http://www.hindawi.com/journals/pd/2012/719167/ The motor examination section of the unified Parkinson’s disease rating scale (UPDRS) is widely used in research but few studies have examined whether subscales exist that tap relatively distinct motor abnormalities. We analyzed data from 193 persons enrolled in a population-based study in Central California. Patients were examined after overnight PD medication washout (“OFF” state) and approximately one hour after taking medication (“ON” state). We performed confirmatory factor analysis of the UPDRS for OFF and ON state examinations; correlations, reliability, and relative validity of resulting subscales were evaluated. A model with five factors (gait/posture, tremor, rigidity, bradykinesia affecting the left extremities, bradykinesia affecting the right extremities) fit the data well, with similar results for OFF and ON states. Internal consistency reliability coefficients were 0.90 or higher for all subscales. The gait/posture subscale most strongly discriminated across levels of patient reported PD symptom severity and of how PD affects them on a daily basis. Compared to the right sided bradykinesia subscale, the left sided bradykinesia subscale had higher discrimination across levels of self-reported PD symptom severity and functional impairment. This supports motor UPDRS containing multiple subscales that can be analyzed separately and provide information distinct from the total score that may be useful in clinical studies. Stefanie D. Vassar, Yvette M. Bordelon, Ron D. Hays, Natalie Diaz, Rebecca Rausch, Cherry Mao, and Barbara G. Vickrey Copyright © 2012 Stefanie D. Vassar et al. All rights reserved. Wed, 17 Oct 2012 15:03:20 +0000 http://www.hindawi.com/journals/pd/2012/943159/ Dyskinetic disorders are characterized by excess of motor activity that may interfere with normal movement control. In patients with Parkinson’s disease, the chronic levodopa treatment induces dyskinetic movements known as levodopa-induced dyskinesias (LID). This paper analyzed the pathophysiology, clinical manifestations, pharmacological treatments, and surgical procedures to treat hyperkinetic disorders. Surgery is currently the only treatment available for Parkinson’s disease that may improve both parkinsonian motor syndrome and LID. However, this paper shows the different mechanisms involved are not well understood. J. Guridi, R. González-Redondo, and J. A. Obeso Copyright © 2012 J. Guridi et al. All rights reserved. Wed, 17 Oct 2012 10:00:38 +0000 http://www.hindawi.com/journals/pd/2012/429524/ It is generally accepted that a correlation between neurodegenerative disease and protein aggregation in the brain exists; however, a causal relationship has not been elucidated. In neurons, failure of autophagy may result in the accumulation of aggregate-prone proteins and subsequent neurodegeneration. Thus, pharmacological induction of autophagy to enhance the clearance of intracytoplasmic aggregate-prone proteins has been considered as a therapeutic strategy to ameliorate pathology in cell and animal models of neurodegenerative disorders. However, autophagy has also been found to be a factor in the onset of these diseases, which raises the question of whether autophagy induction is an effective therapeutic strategy, or, on the contrary, can result in cell death. In this paper, we will first describe the autophagic machinery, and we will consider the literature to discuss the neuroprotective effects of autophagy. Ana María Sánchez-Pérez, Berta Claramonte-Clausell, Juan Vicente Sánchez-Andrés, and María Trinidad Herrero Copyright © 2012 Ana María Sánchez-Pérez et al. All rights reserved. Thu, 27 Sep 2012 08:47:08 +0000 http://www.hindawi.com/journals/pd/2012/424285/ Methamphetamine- (MA-) induced neurotoxicity is associated with mitochondrial dysfunction and enhanced oxidative stress. Our previous study demonstrated that MA induces autophagy in a dopaminergic neuronal cell model (N27 cells). The cellular mechanisms underlying MA-induced autophagy and apoptosis remain poorly characterized. In the present study we sought to investigate the importance of GSH redox status in MA-induced neurotoxicity using a thiol antioxidant, N-acetylcysteine (NAC). Morphological and biochemical analysis revealed that MA-induced autophagy in N27 dopaminergic cells was associated with pronounced depletion of GSH levels. Moreover, pretreatment with NAC reduced MA-induced GSH depletion and autophagy, while depletion of GSH using L-buthionine sulfoximine (L-BSO) enhanced autophagy. Furthermore, treatment with NAC significantly attenuated MA-induced apoptotic cell death as well as oxidative stress markers, namely, 3-nitrotyrosine (3-NT) and 4-hydroxynonenal (4-HNE). Together, these results suggest that NAC exhibits significant protective effects against MA-induced dopaminergic cell death, presumably via modulation of the GSH level and autophagy. Collectively, our data provide mechanistic insights into the role of cellular GSH redox status in MA-induced autophagy and apoptotic cell death, and additional studies are needed to determine the therapeutic effectiveness of cellular redox modifiers in attenuating dopaminergic neurodegeneration in vivo. Prashanth Chandramani Shivalingappa, Huajun Jin, Vellareddy Anantharam, Anumantha Kanthasamy, and Arthi Kanthasamy Copyright © 2012 Prashanth Chandramani Shivalingappa et al. All rights reserved. Wed, 26 Sep 2012 07:29:45 +0000 http://www.hindawi.com/journals/pd/2012/969418/ 17α-Ethynyl-androst-5-ene-3β,7β,17β-triol (HE3286) is a synthetic androstenetriol in Phase II clinical development for the treatment of inflammatory diseases. HE3286 was evaluated for blood-brain barrier (BBB) permeability in mice, and efficacy in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) murine model of Parkinson’s disease (PD). We found that HE3286 freely penetrated the BBB. HE3286 treatment significantly improved motor function compared to vehicle in the rotarod test (mean 58.2 sec versus 90.9 sec, ), and reduced inflammatory mediator gene expression in the brain (inducible nitric oxide synthase, 20%, ; tumor necrosis factor α, 40%, , and interleukin-1β, 33%, ) measured by reverse-transcriptase polymerase chain reaction. Brain tissue histopathology and immunohistochemistry showed that HE3286 treatment increased the numbers of tyrosine hydroxylase-positive cells by 17% compared to vehicle (), and decreased the numbers of damaged neurons by 38% relative to vehicle (). L-3,4-dihydroxyphenylalanine (L-DOPA) efficacy was not enhanced by concurrent administration of HE3286. HE3286 administration prior to MPTP did not enhance efficacy. Our data suggest a potential role for HE3286 in PD treatment, and provides incentive for further investigation. Ferdinando Nicoletti, Ingrid Philippens, Paolo Fagone, Clarence N. Ahlem, Christopher L. Reading, James M. Frincke, and Dominick L. Auci Copyright © 2012 Ferdinando Nicoletti et al. All rights reserved. Tue, 18 Sep 2012 13:46:16 +0000 http://www.hindawi.com/journals/pd/2012/907513/ Jessica Calleo, Cristina Burrows, Harvey Levin, Laura Marsh, Eugene Lai, and Michele K. York Copyright © 2012 Jessica Calleo et al. All rights reserved. Sun, 16 Sep 2012 14:16:52 +0000 http://www.hindawi.com/journals/pd/2012/729428/ Yuzuru Imai, Katerina Venderova, and Kah-Leong Lim Copyright © 2012 Yuzuru Imai et al. All rights reserved. Thu, 30 Aug 2012 15:56:03 +0000 http://www.hindawi.com/journals/pd/2012/308097/ Neuropsychiatric symptoms commonly complicate Parkinson’s disease (PD), however the presence of such symptoms in mild cognitive impairment (PD-MCI) specifically has not yet been well described. The objective of this study was to examine and compare the prevalence and profile of neuropsychiatric symptoms in patients with PD-MCI (n = 48) to those with PD and no cognitive impairment (PD-NC, n = 54) and to those with dementia in PD (PDD, n = 25). PD-MCI and PDD were defined using specific consensus criteria, and neuropsychiatric symptoms were assessed with the 12-item Neuropsychiatric Inventory (NPI). Self-rated apathy, depression, and anxiety rating scales were also administered. Over 79% of all participants reported at least one neuropsychiatric symptom in the past month. The proportion in each group who had total NPI scores of ≥4 (“clinically significant”) was as follows: PD-NC, 64.8%; PD-MCI, 62%; PDD 76%. Apathy was reported in almost 50% of those with PD-MCI and PDD, and it was an important neuropsychiatric symptom differentiating PD-MCI from PD-NC. Psychosis (hallucinations and delusions) increased from 12.9% in PD-NC group; 16.7% in PD-MCI group; and 48% in PDD group. Identifying neuropsychiatric symptoms in PD-MCI may have implications for ascertaining conversion to dementia in PD. Iracema Leroi, Hiranmayi Pantula, Kathryn McDonald, and Vijay Harbishettar Copyright © 2012 Iracema Leroi et al. All rights reserved. Thu, 30 Aug 2012 08:43:16 +0000 http://www.hindawi.com/journals/pd/2012/151039/ Parkinson's disease is the second common neurodegenerative disorder, after Alzheimer's disease. It is a clinical syndrome characterized by loss of dopamine-generating cells in the substancia nigra, a region of the midbrain. The etiology of Parkinson's disease has long been through to involve both genetic and environmental factors. Mutations in the leucine-rich repeat kinase 2 gene cause late-onset Parkinson's disease with a clinical appearance indistinguishable from Parkinson's disease idiopathic. Autophagy is an intracellular catabolic mechanism whereby a cell recycles or degrades damage proteins and cytoplasmic organelles. This degradative process has been associated with cellular dysfunction in neurodegenerative processes including Parkinson's disease. We discuss the role of leucine-rich repeat kinase 2 in autophagy, and how the deregulations of this degradative mechanism in cells can be implicated in the Parkinson's disease etiology. José M. Bravo-San Pedro, Rubén Gómez-Sánchez, Elisa Pizarro-Estrella, Mireia Niso-Santano, Rosa A. González-Polo, and José M. Fuentes Rodríguez Copyright © 2012 José M. Bravo-San Pedro et al. All rights reserved.