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  • Brainstem ventilatory dysfunction: A plausible mechanism for dyspnea in Parkinson's Disease?
    Mov. Disord. (IF 8.061) Pub Date : 2020-01-15
    Srimathy Vijayan; Bhajan Singh; Soumya Ghosh; Rick Stell; Frank L Mastaglia

    Dyspnea is an under‐recognized and debilitating symptom that is reported in up to 40% of patients with Parkinson's disease and may have multiple origins. Despite its frequency, it is poorly researched, and there is a general lack of understanding of the pathophysiology of dyspnea and respiratory dysfunction in PD. Consequently, a number of PD patients are labelled as having “unexplained dyspnea.” Studies to date have focused mainly on evaluating ventilatory capacity and lung volumes, and little is known about the effects of the disease on the medullary and pontine ventilatory control centers within the brainstem. This is of particular relevance in view of neuropathological studies demonstrating early involvement of the dorsal medulla and other brainstem structures by the disease process. The possibility that impaired brainstem ventilatory control is a contributory mechanism for dyspnea and could be a premotor manifestation in some PD patients therefore warrants further attention. This review focuses on clinical, pathological, and experimental evidence for the involvement of brainstem respiratory centers in PD. We highlight the need for further research, particularly in PD patients with unexplained dyspnea. © 2019 International Parkinson and Movement Disorder Society

  • Normal temporal discrimination in musician's dystonia is linked to aberrant sensorimotor processing
    Mov. Disord. (IF 8.061) Pub Date : 2020-01-13
    Fiachra Maguire; Richard B. Reilly; Kristina Simonyan

    Alterations in sensory discrimination are a prominent nonmotor feature of dystonia. Abnormal temporal discrimination in focal dystonia is considered to represent its mediational endophenotype, albeit unclear pathophysiological correlates. We examined the associations between the visual temporal discrimination threshold (TDT) and brain activity in patients with musician's dystonia, nonmusician's dystonia, and healthy controls.

  • Subthalamic nucleus stimulation impairs motivation: Implication for apathy in Parkinson's disease
    Mov. Disord. (IF 8.061) Pub Date : 2020-01-13
    Yvan Vachez; Carole Carcenac; Robin Magnard; Lydia Kerkerian‐Le Goff; Pascal Salin; Marc Savasta; Sebastien Carnicella; Sabrina Boulet

    Apathy is one of the most disabling neuropsychiatric symptoms in Parkinson's disease (PD) patients and has a higher prevalence in patients under subthalamic nucleus deep brain stimulation. Indeed, despite its effectiveness for alleviating PD motor symptoms, its neuropsychiatric repercussions have not yet been fully uncovered. Because it can be alleviated by dopaminergic therapies, especially D2 and D3 dopaminergic receptor agonists, the commonest explanation proposed for apathy after subthalamic nucleus deep brain stimulation is a too‐strong reduction in dopaminergic treatments. The objective of this study was to determine whether subthalamic nucleus deep brain stimulation can induce apathetic behaviors, which remains an important matter of concern. We aimed to unambiguously address this question of the motivational effects of chronic subthalamic nucleus deep brain stimulation.

  • Role of glial cell line‐derived neurotrophic factor in the maintenance of adult mesencephalic catecholaminergic neurons
    Mov. Disord. (IF 8.061) Pub Date : 2020-01-13
    Daniel Enterría‐Morales; Ivette López‐López; José López‐Barneo; Xavier d'Anglemont de Tassigny

    The glial cell line‐derived neurotrophic factor has a potent neuroprotective action on mesencephalic dopamine neurons, which are progressively lost in Parkinson's disease. Intrastriatal administration of this factor is a promising therapy for Parkinson's disease. Glial cell line‐derived neurotrophic factor is naturally produced in restricted cerebral regions, such as the striatum, septum, and thalamus; however, its effects in the adult brain remain under debate.

  • CLU rs11136000 promotes early cognitive decline in Parkinson's disease
    Mov. Disord. (IF 8.061) Pub Date : 2020-01-13
    Frederic Sampedro; Juan Marín‐Lahoz; Saul Martínez‐Horta; Rocío Pérez‐González; Javier Pagonabarraga; Jaime Kulisevsky

    The C allele of the rs11136000 genetic variant of the clusterin gene has been associated with increased risk of Alzheimer's disease. However, a comprehensive characterization of the role of this genetic variant in early cognitive deterioration in PD is lacking.

  • Aberrant somatosensory–motor adaptation in musicians' dystonia
    Mov. Disord. (IF 8.061) Pub Date : 2020-01-10
    Shinichi Furuya; André Lee; Takanori Oku; Eckart Altenmüller

    Some forms of movement disorders are characterized by task‐specific manifestations of symptoms. However, its underlying mechanisms are poorly understood. Here we addressed this issue through a novel motor adaptation experimental paradigm.

  • Early‐motor phenotype relates to neuropsychiatric and cognitive disorders in huntington's disease
    Mov. Disord. (IF 8.061) Pub Date : 2020-01-10
    Parunyou Julayanont; Kenneth M. Heilman; Nikolaus R. McFarland

    To determine the relationships between the motor phenotype and the presence of specific neuropsychiatric and neuropsychological disorders in patients with early motor‐manifest Huntington's disease (HD).

  • Loss‐of‐function mutations in NR4A2 cause dopa‐responsive dystonia Parkinsonism
    Mov. Disord. (IF 8.061) Pub Date : 2020-01-10
    Thomas Wirth; Louise Laure Mariani; Gaber Bergant; Michel Baulac; Marie‐Odile Habert; Nathalie Drouot; Emmanuelle Ollivier; Alenka Hodžić; Gorazd Rudolf; Patrick Nitschke; Gabrielle Rudolf; Jamel Chelly; Christine Tranchant; Mathieu Anheim; Emmanuel Roze

    The group of dystonia genes is expanding, and mutations of these genes have been associated with various combined dystonia syndromes. Among the latter, the cause of some dystonia parkinsonism cases remains unknown.

  • Anatomo‐functional mapping of the primate mesencephalic locomotor region using stereotactic lesions
    Mov. Disord. (IF 8.061) Pub Date : 2020-01-10
    Marion Gay; Hayat Belaid; Alister Rogers; Fernando Pérez‐García; Maxime Roustan; Eric Bardinet; Chantal François; Carine Karachi

    Dysfunction of the mesencephalic locomotor region has been implicated in gait disorders. However, the role of its 2 components, the pedunculopontine and the cuneiform nuclei, in locomotion is poorly understood in primates.

  • Pallidal Deep Brain Stimulation Reduces Sensorimotor Cortex Activation in Focal/Segmental Dystonia
    Mov. Disord. (IF 8.061) Pub Date : 2020-01-10
    Andrea Greuel; K. Amande M. Pauls; Anne Koy; Martin Südmeyer; Alfons Schnitzler; Lars Timmermann; Gereon R. Fink; Carsten Eggers

    Although deep brain stimulation of the globus pallidus internus (GPi‐DBS) is an established treatment for many forms of dystonia, including generalized as well as focal forms, its effects on brain (dys‐)function remain to be elucidated, particularly for focal and segmental dystonia. Clinical response to GPi‐DBS typically comes with some delay and lasts up to several days, sometimes even weeks, once stimulation is discontinued.

  • Decreased Penetrance of Parkinson's Disease in Elderly Carriers of Glucocerebrosidase Gene L444P/R Mutations: A Community‐Based 10‐Year Longitudinal Study
    Mov. Disord. (IF 8.061) Pub Date : 2020-01-08
    Shaozhen Ji; Chaodong Wang; Hongwen Qiao; Zhuqin Gu; Ziv Gan‐Or; Edward A. Fon; Piu Chan

    Heterozygous mutations in the glucocerebrosidase gene (GBA) have been shown to be an important genetic risk factor for Parkinson's disease (PD) worldwide. However, the penetrance of GBA heterozygote for L444P, the common mutation for Asian population, is not known in older Chinese people.

  • Brain mitochondrial impairment in early‐onset Parkinson's disease with or without PINK1 mutation
    Mov. Disord. (IF 8.061) Pub Date : 2020-01-02
    Mario Rango; Gabriele Dossi; Letizia Squarcina; Cristiana Bonifati

    PINK1 mutations are likely to affect mitochondrial function. The objective of this study was to study brain mitochondrial function in patients with early‐onset Parkinson's disease, with or without PINK1 mutations.

  • Meta‐analysis of copper and iron in Parkinson's disease brain and biofluids
    Mov. Disord. (IF 8.061) Pub Date : 2019-12-31
    Sian Genoud; Alistair M. Senior; Dominic J. Hare; Kay L. Double

    Variations in study quality and design complicate interpretation of the clinical significance of consistently reported changes in copper and iron levels in human Parkinson's disease brain and biofluids.

  • Metabolic network abnormalities in drug‐naïve Parkinson's Disease
    Mov. Disord. (IF 8.061) Pub Date : 2019-12-24
    Katharina A. Schindlbeck; Olaia Lucas‐Jiménez; Chris C. Tang; Silvia Morbelli; Dario Arnaldi; Matteo Pardini; Marco Pagani; Naroa Ibarretxe‐Bilbao; Natalia Ojeda; Flavio Nobili; David Eidelberg

    An ideal imaging biomarker for a neurodegenerative disorder should be able to measure abnormalities in the earliest stages of the disease.

  • Cardiac noradrenaline turnover and heat shock protein 27 phosphorylation in dyskinetic monkeys
    Mov. Disord. (IF 8.061) Pub Date : 2019-12-24
    Pilar Almela; Lorena Cuenca‐Bermejo; José E. Yuste; Cristina Estrada; Vicente de Pablos; Víctor Bautista‐Hernández; Emiliano Fernández‐Villalba; María‐Luisa Laorden; María‐Trinidad Herrero

    Autonomic dysfunction is a well‐known dominant symptom in the advanced stages of Parkinson's disease. However, the role of cardiac sympathetic nerves still needs to be elucidated.

  • Dyskinesia matters
    Mov. Disord. (IF 8.061) Pub Date : 2019-12-24
    M. Angela Cenci; Sara Riggare; Rajesh Pahwa; David Eidelberg; Robert A. Hauser

    Levodopa‐induced dyskinesia (LID) represents a significant source of discomfort for people with Parkinson's disease (PD). It negatively affects quality of life, it is associated with both motor and nonmotor fluctuations, and it brings an increased risk of disability, balance problems, and falls. Although the prevalence of severe LID appears to be lower than in previous eras (likely owing to a more conservative use of oral levodopa), we have not yet found a way to prevent the development of this complication. Advanced surgical therapies, such as deep brain stimulation, ameliorate LID, but only a minority of PD patients qualify for these interventions. Although some have argued that PD patients would rather be ON with dyskinesia than OFF, the deeper truth is that patients would very much prefer to be ON without dyskinesia. As researchers and clinicians, we should aspire to make that goal a reality. To this end, translational research on LID is to be encouraged and persistently pursued. © 2019 International Parkinson and Movement Disorder Society

  • Little Change in Functional Brain Networks Following Acute Levodopa in Drug‐Naïve Parkinson's Disease
    Mov. Disord. (IF 8.061) Pub Date : 2019-12-19
    Robert L. White; Meghan C. Campbell; Dake Yang; William Shannon; Abraham Z. Snyder; Joel S. Perlmutter

    The objective of this study was to investigate the effects of levodopa on functional brain networks in Parkinson's disease.

  • Quantitative evaluation of iron content in idiopathic rapid eye movement sleep behavior disorder
    Mov. Disord. (IF 8.061) Pub Date : 2019-12-17
    Junyan Sun; Zhaoyu Lai; Jinghong Ma; Linlin Gao; Meijie Chen; Jie Chen; Jiliang Fang; Yangyang Fan; Yan Bao; Dongling Zhang; Piu Chan; Qi Yang; Chenfei Ye; Tao Wu; Ting Ma

    Idiopathic rapid eye movement sleep behavior disorder is an early sign of neurodegenerative disease. This study aimed to quantitatively evaluate iron content in idiopathic rapid eye movement sleep behavior disorder patients using quantitative susceptibility mapping and to examine the potential of this technique to identify the prodromal stage of α‐synucleinopathies.

  • Metabolic correlates of dopaminergic loss in dementia with lewy bodies
    Mov. Disord. (IF 8.061) Pub Date : 2019-12-16
    Maria Huber; Leonie Beyer; Catharina Prix; Sonja Schönecker; Carla Palleis; Boris‐Stephan Rauchmann; Silvia Morbelli; Andrea Chincarini; Rose Bruffaerts; Rik Vandenberghe; Koen Van Laere; Milica G. Kramberger; Maja Trost; Marko Grmek; Valentina Garibotto; Nicolas Nicastro; Giovanni B. Frisoni; Afina W. Lemstra; Jessica van der Zande; Andrea Pilotto; Alessandro Padovani; Sara Garcia‐Ptacek; Irina Savitcheva; Miguel A Ochoa‐Figueroa; Anette Davidsson; Valle Camacho; Enrico Peira; Dario Arnaldi; Matteo Bauckneht; Matteo Pardini; Gianmario Sambuceti; Jonathan Vöglein; Jonas Schnabel; Marcus Unterrainer; Robert Perneczky; Oliver Pogarell; Katharina Buerger; Cihan Catak; Peter Bartenstein; Paul Cumming; Michael Ewers; Adrian Danek; Johannes Levin; Dag Aarsland; Flavio Nobili; Axel Rominger; Matthias Brendel

    Striatal dopamine deficiency and metabolic changes are well‐known phenomena in dementia with Lewy bodies and can be quantified in vivo by 123I‐Ioflupane brain single‐photon emission computed tomography of dopamine transporter and 18F‐fluorodesoxyglucose PET. However, the linkage between both biomarkers is ill‐understood.

  • Glial cell line–derived neurotrophic factor receptor REarranged during transfection agonist supports dopamine neurons in Vitro and enhances dopamine release In Vivo
    Mov. Disord. (IF 8.061) Pub Date : 2019-12-16
    Arun Kumar Mahato; Jaakko Kopra; Juho‐Matti Renko; Tanel Visnapuu; Ilari Korhonen; Nita Pulkkinen; Maxim M. Bespalov; Andrii Domanskyi; Eric Ronken; T. Petteri Piepponen; Merja H. Voutilainen; Raimo K. Tuominen; Mati Karelson; Yulia A. Sidorova; Mart Saarma

    Motor symptoms of Parkinson's disease (PD) are caused by degeneration and progressive loss of nigrostriatal dopamine neurons. Currently, no cure for this disease is available. Existing drugs alleviate PD symptoms but fail to halt neurodegeneration. Glial cell line–derived neurotrophic factor (GDNF) is able to protect and repair dopamine neurons in vitro and in animal models of PD, but the clinical use of GDNF is complicated by its pharmacokinetic properties. The present study aimed to evaluate the neuronal effects of a blood‐brain‐barrier penetrating small molecule GDNF receptor Rearranged in Transfection agonist, BT13, in the dopamine system.

  • Cerebrospinal fluid levels of neurogranin in Parkinsonian disorders
    Mov. Disord. (IF 8.061) Pub Date : 2019-12-13
    Sara Hall; Shorena Janelidze; Henrik Zetterberg; Britta Brix; Niklas Mattsson; Yulia Surova; Kaj Blennow; Oskar Hansson

    CSF concentration of neurogranin has been suggested as a biomarker for synapse dysfunction.

  • Transcranial ultrasound stimulation directly influences the cortical excitability of the motor cortex in Parkinsonian mice
    Mov. Disord. (IF 8.061) Pub Date : 2019-12-12
    Zhijie Wang; Jiaqing Yan; Xingrang Wang; Yi Yuan; Xiaoli Li

    Low‐intensity transcranial ultrasound stimulation is a new noninvasive brain modulation method with high spatial resolution and high penetration depth. However, until now, it was unclear whether transcranial ultrasound stimulation has a significant effect on PD.

  • The role of the cerebellum in degenerative ataxias and essential tremor: Insights from noninvasive modulation of cerebellar activity
    Mov. Disord. (IF 8.061) Pub Date : 2019-12-10
    Roderick P.P.W.M. Maas, Rick C.G. Helmich, Bart P.C. van de Warrenburg

    Over the last three decades, measuring and modulating cerebellar activity and its connectivity with other brain regions has become an emerging research topic in clinical neuroscience. The most important connection is the cerebellothalamocortical pathway, which can be functionally interrogated using a paired‐pulse transcranial magnetic stimulation paradigm. Cerebellar brain inhibition reflects the magnitude of suppression of motor cortex excitability after stimulating the contralateral cerebellar hemisphere and therefore represents a neurophysiological marker of the integrity of the efferent cerebellar tract. Observations that cerebellar noninvasive stimulation techniques enhanced performance of certain motor and cognitive tasks in healthy individuals have inspired attempts to modulate cerebellar activity and connectivity in patients with cerebellar diseases in order to achieve clinical benefit. We here comprehensively explore the therapeutic potential of these techniques in two movement disorders characterized by prominent cerebellar involvement, namely the degenerative ataxias and essential tremor. The article aims to illustrate the (patho)physiological insights obtained from these studies and how these translate into clinical practice, where possible by addressing the association with cerebellar brain inhibition. Finally, possible explanations for some discordant interstudy findings, shortcomings in our current understanding, and recommendations for future research will be provided. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

  • Circulating Brain‐enriched MicroRNAs for detection and discrimination of idiopathic and genetic Parkinson's disease
    Mov. Disord. (IF 8.061) Pub Date : 2019-12-04
    Stylianos Ravanidis, Anastasia Bougea, Nikolaos Papagiannakis, Matina Maniati, Christos Koros, Athina‐Maria Simitsi, Maria Bozi, Ioanna Pachi, Maria Stamelou, George P. Paraskevas, Elisabeth Kapaki, Marina Moraitou, Helen Michelakakis, Leonidas Stefanis, Epaminondas Doxakis

    A minimally invasive test for early detection and monitoring of Parkinson's disease (PD) is a highly unmet need for drug development and planning of patient care. Blood plasma represents an attractive source of biomarkers. MicroRNAs (miRNAs) are conserved noncoding RNA molecules that serve as posttranscriptional regulators of gene expression. As opposed to ubiquitously expressed miRNAs that control house‐keeping processes, brain‐enriched miRNAs regulate diverse aspects of neuron development and function. These include neuron‐subtype specification, axonal growth, dendritic morphogenesis, and spine density. Backed by a large number of studies, we now know that the differential expression of neuron‐enriched miRNAs leads to brain dysfunction.

  • Swimming Is Compromised in Parkinson's Disease Patients
    Mov. Disord. (IF 8.061) Pub Date : 2019-12-04
    Maria Ana Neves, Raquel Bouça‐Machado, Daniela Guerreiro, Verónica Caniça, Filipa Pona‐Ferreira, Joaquim J. Ferreira

    A recent survey reported a high risk of drowning in Parkinson's disease (PD) patients. This study intended to assess PD patients’ swimming ability and explore the disease‐related characteristics that may affect this.

  • Effectiveness of Physiotherapy on Freezing of Gait in Parkinson's Disease: A Systematic Review and Meta‐Analyses
    Mov. Disord. (IF 8.061) Pub Date : 2019-12-04
    Carola Cosentino, Marco Baccini, Martina Putzolu, Diego Ristori, Laura Avanzino, Elisa Pelosin

    Freezing of gait is considered one of the most disabling gait disorders in patients with PD. An effective treatment for freezing of gait is missing, thus current management requires a multidisciplinary approach. Among treatment options, physiotherapy is acknowledged to be crucial; however, a systematic review that demonstrates its efficacy is missing. This review aims at examining the short‐ and long‐term effects of physiotherapy in improving freezing of gait in PD patients. Five electronic databases were searched for English‐language full‐text articles, and only randomized controlled trials were considered. The freezing of gait questionnaire was selected as the primary outcome measure because it is the only validated measure used to evaluate the severity and impact of freezing of gait on patients’ daily life. From 1,130 trials, 19 relevant studies, including 913 patients, were selected. The included studies varied for sample size, methodology, and type of intervention. None of the studies had a low risk of bias, but the majority of randomized control trials presented a low risk for at least 6 of 13 biases. Our findings provide evidence for short‐term effectiveness of physiotherapy in improving freezing of gait (physiotherapy vs. no treatment: effect size = –0.28 [–0.45, –0.11], P = 0.001; physiotherapy vs. control: effect size = 0.43 [–0.65, –0.21], P < 0.0001), particularly when tailored interventions are applied. These results seem to be maintained at the follow‐up examinations (effect size = –0.52 [–0.78, –0.26]; P = 0.001). Promising findings on the potential benefits of physiotherapy in improving freezing of gait were found, although further randomized control trial studies are still needed. Questions remain on the type and duration of intervention that best fits for treating freezing of gait symptom in PD. © 2019 International Parkinson and Movement Disorder Society

  • Salivary microR‐153 and microR‐223 Levels as Potential Diagnostic Biomarkers of Idiopathic Parkinson's Disease
    Mov. Disord. (IF 8.061) Pub Date : 2019-12-04
    Marisa Cressatti, Lamin Juwara, Julia M. Galindez, Ana M. Velly, Eva S. Nkurunziza, Sara Marier, Olivia Canie, Mervyn Gornistky, Hyman M. Schipper

    Parkinson's disease (PD) is the most common movement disorder among adults, affecting 2% of the world population older than 65 years of age. No diagnostic biomarker for routine use in clinical settings currently exists. Dysregulation of microRNAs (miRNAs) has been implicated in various neurodegenerative conditions, including PD. Distinct miRNAs have been demonstrated to be involved in the regulation of α‐synuclein, a key player in PD pathogenesis; miR‐153 and miR‐223 are downregulated in the brain and serum of parkinsonian GFAP.HMOX1 transgenic mice where they directly regulate α‐synuclein.

  • Changes in thalamic dopamine innervation in a progressive Parkinson's disease model in monkeys
    Mov. Disord. (IF 8.061) Pub Date : 2019-12-04
    Mariana H.G. Monje, Javier Blesa, Miguel Ángel García‐Cabezas, José A. Obeso, Carmen Cavada

    Dopamine loss beyond the mesostriatal system might be relevant in pathogenic mechanisms and some clinical manifestations in PD. The primate thalamus is densely and heterogeneously innervated with dopaminergic axons, most of which express the dopamine transporter, as does the nigrostriatal system. We hypothesized that dopamine depletion may be present in the thalamus of the parkinsonian brain and set out to ascertain possible regional differences.

  • Clinical Evaluation of Sibling Pairs With Gaucher Disease Discordant for Parkinsonism
    Mov. Disord. (IF 8.061) Pub Date : 2019-11-30
    Grisel Lopez, Alta Steward, Emory Ryan, Catherine Groden, Edythe Wiggs, Laura Segalà, Gianina M. Monestime, Nahid Tayebi, Ellen Sidransky

    Although the association between mutations in GBA1 and parkinsonism is well established, most GBA1 mutation carriers never develop parkinsonism, implicating the contribution of other genetic, epigenetic, and/or environmental modifiers.

  • Body mass index, diabetes, and the risk of Parkinson's disease
    Mov. Disord. (IF 8.061) Pub Date : 2019-11-30
    Su‐Min Jeong, Kyungdo Han, Dahye Kim, Sang Youl Rhee, Wooyoung Jang, Dong Wook Shin

    There are conflicting findings in the literature regarding the association of body mass index and incidence of PD.

  • Cervical dystonia incidence and diagnostic delay in a multiethnic population
    Mov. Disord. (IF 8.061) Pub Date : 2019-11-27
    Sara C. LaHue, Kathleen Albers, Samuel Goldman, Raymond Lo, Zhuqin Gu, Amethyst Leimpeter, Robin Fross, Kathleen Comyns, Connie Marras, Annelie de Kleijn, Robin Smit, Maya Katz, Laurie J. Ozelius, Susan Bressman, Rachel Saunders‐Pullman, Cynthia Comella, Jeffrey Klingman, Lorene M. Nelson, Stephen K. Van Den Eeden, Caroline M. Tanner

    Current cervical dystonia (CD) incidence estimates are based on small numbers in relatively ethnically homogenous populations. The frequency and consequences of delayed CD diagnosis is poorly characterized.

  • Alcohol intake and Parkinson's disease risk in the million women study
    Mov. Disord. (IF 8.061) Pub Date : 2019-11-26
    Iris Y. Kim, TienYu Owen Yang, Alicia K. Heath, Rachel F. Simpson, Gillian K. Reeves, Jane Green, Sarah Floud, Anna Brown, David J. Hunter, Valerie Beral, Siân Sweetland,

    Alcohol intake may be associated with a lower risk of Parkinson's disease (PD), but findings from previous studies have been inconclusive.

  • Nonpharmacological, Nonsurgical Treatments for Freezing of Gait in Parkinson's Disease: A Systematic Review
    Mov. Disord. (IF 8.061) Pub Date : 2019-11-26
    Manuel Delgado‐Alvarado, Massimo Marano, Ana Santurtún, Ainhoa Urtiaga‐Gallano, Diana Tordesillas‐Gutierrez, Jon Infante

    Freezing of gait is a disabling phenomenon that appears in a substantial number of Parkinson's disease (PD) patients as the disease evolves. It is considered to be one of the most relevant contributing factors to worsening of quality of life. Current pharmacological or surgical treatment options have limited efficacy. Thus, alternative nonpharmacological/nonsurgical approaches have emerged in recent years in an attempt to improve quality of life in PD. This systematic review summarizes studies of such therapies over the past 5 years. Thirty‐five studies were evaluated by use of a qualitative evaluation, while the methodological quality was assessed using validated tools. According to our results, there appear to be two broad categories of nonpharmacological therapies: those that seek a long‐lasting benefit and those that aim to achieve a transient effect to overcome the freezing of gait episode. Among the former, it is possible to differentiate between “passive” therapies, which include transcranial magnetic stimulation or transcranial direct current stimulation, and “active” therapies, which are based on different cognitive or physical training programs. Finally, “transient effect” therapies use different types of cues, such as visual, auditory, or proprioceptive stimuli, to attempt to shift the patient's habitual motor control to a goal‐directed one. In conclusion, a broad spectrum of nonpharmacological/nonsurgical approaches for freezing of gait has emerged in recent years with promising results. © 2019 International Parkinson and Movement Disorder Society

  • Computer Mouse Use Captures Ataxia and Parkinsonism, Enabling Accurate Measurement and Detection
    Mov. Disord. (IF 8.061) Pub Date : 2019-11-25
    Krzysztof Z. Gajos, Katharina Reinecke, Mary Donovan, Christopher D. Stephen, Albert Y. Hung, Jeremy D. Schmahmann, Anoopum S. Gupta

    Objective assessments of movement impairment are needed to support clinical trials and facilitate diagnosis. The objective of the current study was to determine if a rapid web‐based computer mouse test (Hevelius) could detect and accurately measure ataxia and parkinsonism.

  • α‐Synuclein real‐time quaking‐induced conversion in the submandibular glands of Parkinson's disease patients
    Mov. Disord. (IF 8.061) Pub Date : 2019-11-23
    Sireesha Manne, Naveen Kondru, Huajun Jin, Vellareddy Anantharam, Xuemei Huang, Arthi Kanthasamy, Anumantha G. Kanthasamy

    Identification of a peripheral biomarker is a major roadblock in the diagnosis of PD. Immunohistological identification of p‐serine 129 α‐synuclein in the submandibular gland tissues of PD patients has been recently reported.

  • Texture features of magnetic resonance images: A marker of slight cognitive deficits in Parkinson's disease
    Mov. Disord. (IF 8.061) Pub Date : 2019-11-23
    Nacim Betrouni, Renaud Lopes, Luc Defebvre, Albert F. G. Leentjens, Kathy Dujardin

    Cognitive impairment is a frequent nonmotor symptom of Parkinson's disease. Depending on severity, patients are considered to have mild cognitive impairment or dementia. However, among the cognitively intact patients, some may have deficits in a less severe range. The early detection of such subtle symptoms may be important for the initiation of care strategies.

  • Theta‐alpha oscillations characterize emotional subregion in the human ventral subthalamic nucleus
    Mov. Disord. (IF 8.061) Pub Date : 2019-11-23
    Pnina Rappel, Shai Grosberg, David Arkadir, Eduard Linetsky, Muneer Abu Snineh, Atira S. Bick, Idit Tamir, Dan Valsky, Odeya Marmor, Yasmin Abo Foul, Or Peled, Moran Gilad, Chen Daudi, Shiri Ben‐Naim, Hagai Bergman, Zvi Israel, Renana Eitan

    Therapeutic outcomes of STN‐DBS for movement and psychiatric disorders depend on electrode location within the STN. Electrophysiological and functional mapping of the STN has progressed considerably in the past years, identifying beta‐band oscillatory activity in the dorsal STN as a motor biomarker. It also has been suggested that STN theta‐alpha oscillations, involved in impulse control and action inhibition, have a ventral source. However, STN local field potential mapping of motor, associative, and limbic areas is often limited by poor spatial resolution.

  • Deep Brain Stimulation for Freezing of Gait in Parkinson's Disease With Early Motor Complications
    Mov. Disord. (IF 8.061) Pub Date : 2019-11-22
    Michael T. Barbe, Lisa Tonder, Paul Krack, Bettina Debû, Michael Schüpbach, Steffen Paschen, Till A. Dembek, Andrea A. Kühn, Valerie Fraix, Christine Brefel‐Courbon, Lars Wojtecki, David Maltête, Phillippe Damier, Friederike Sixel‐Döring, Daniel Weiss, Marcus Pinsker, Tatiana Witjas, Stephane Thobois, Carmen Schade‐Brittinger, Jörn Rau, Jean‐Luc Houeto, Andreas Hartmann, Lars Timmermann, Alfons Schnitzler, Valerie Stoker, Marie Vidailhet, Günther Deuschl,

    Effects of DBS on freezing of gait and other axial signs in PD patients are unclear.

  • Early‐stage Parkinson's patients show selective impairment in reactive but not proactive inhibition
    Mov. Disord. (IF 8.061) Pub Date : 2019-11-21
    Veronica Di Caprio, Nicola Modugno, Christian Mancini, Enrica Olivola, Giovanni Mirabella

    It is well known that a deficit in inhibitory control is a hallmark of Parkinson's disease (PD). However, inhibition is not a unitary construct, and it is unclear whether patients in the early stage of the disease (Hoehn and Yahr stage 1) exhibit a deficit in outright stopping (reactive inhibition), a deficit in the ability to shape their response strategies according to the context (proactive inhibition), or both.

  • The largest caucasian kindred with dentatorubral‐pallidoluysian atrophy: A founder mutation in italy
    Mov. Disord. (IF 8.061) Pub Date : 2019-11-21
    Silvia Grimaldi, Chiara Cupidi, Nicoletta Smirne, Livia Bernardi, Fabio Giacalone, Giuseppina Piccione, Salvatore Basiricò, Giuseppe Donato Mangano, Rosaria Nardello, Laura Orsi, Enrico Grosso, Valentina Laganà, Micaela Mitolo, Raffaele Giovanni Maletta, Amalia Cecilia Bruni

    Dentatorubral‐pallidoluysian atrophy is a hereditary neurodegenerative disease prevalently reported in Japan but rare in Caucasians. The objective of this study was to reconstruct the pedigree of Italian dentatorubral‐pallidoluysian atrophy familial cases describing their clinical features.

  • Prevalence and clinical aspects of mild cognitive impairment in Parkinson's disease: A meta‐analysis
    Mov. Disord. (IF 8.061) Pub Date : 2019-11-19
    Chiara Baiano, Paolo Barone, Luigi Trojano, Gabriella Santangelo

    Mild cognitive impairment associated with Parkinson's disease (PD) is a risk factor for the development of dementia. Despite the importance of early identification of mild cognitive impairment in PD, its prevalence and clinical correlates are still debated. The present meta‐analysis provides a robust estimate of prevalence rate of mild cognitive impairment in PD according to the Movement Disorder Society clinical criteria and to explore the differences between PD patients with and without mild cognitive impairment in demographic, clinical, and neuropsychiatric features. A systematic literature search was performed up to April 2019 using PsycInfo (PROQUEST), PubMed, and Scopus. From 4706 titles and abstracts, 41 studies were selected (n = 7053 patients). Pooled mild cognitive impairment prevalence was 40% on a total sample of 7053 PD patients (95% confidence interval = 36–44; Q = 490.14, P < 0.0001; I2 = 91.84%) with a higher frequency for the multiple domain subtype (31%; 95% confidence interval = 23–41, Q = 93.24; P < 0.0001; I2 = 92.49%). Meta‐regression analysis revealed that stage of PD moderate prevalence estimates of mild cognitive impairment (β = 2.80; P = 0.008). Mild cognitive impairment in PD was associated with older age, lower education, longer disease duration, higher levodopa equivalent daily dose, more severe motor symptoms, and postural instability/gait difficulty motor subtype, poorer quality of life, higher levels of apathy, and depression. The present meta‐analysis indicated that mild cognitive impairment in PD is a frequent cognitive status deserving to be early detected by means of standardized cognitive assessments in clinical practice. © 2019 International Parkinson and Movement Disorder Society

  • The anterior caudate nucleus supports impulsive choices triggered by pramipexole
    Mov. Disord. (IF 8.061) Pub Date : 2019-11-18
    Eva Martinez, Benjamin Pasquereau, Yosuke Saga, Élise Météreau, Léon Tremblay

    Pramipexole is a dopamine agonist used as a treatment in PD and restless legs syndrome to reduce motor symptoms, but it often induces impulse control disorders. In particular, patients with impulse control disorders tend to make more impulsive choices in the delay discounting task, that is, they choose small immediate rewards over larger delayed ones more often than patients without impulse control disorders and healthy subjects do. Yet the site of action of pramipexole that produces these impulsive choices remains unknown. Based on the heterogeneity of corticostriatal projections and the massive dopamine innervation of the striatum, we hypothesized that impulsive choices triggered by dopamine treatments may be supported by a specific striatal territory.

  • CSF or serum neurofilament light added to α‐Synuclein panel discriminates Parkinson's from controls
    Mov. Disord. (IF 8.061) Pub Date : 2019-11-18
    Linda P. Oosterveld, Inge M.W. Verberk, Nour K. Majbour, Omar M. El‐Agnaf, Henry C. Weinstein, Henk W. Berendse, Charlotte E. Teunissen, Wilma D.J. van de Berg

    Neurofilament light chain is a marker of axonal damage and is of interest as a biofluid biomarker for PD. The objective of this study was to investigate whether CSF or serum neurofilament contributes to a combination of CSF biomarkers in defining the optimal biomarker panel for discriminating PD patients from healthy controls. In addition, we aimed to assess whether CSF and/or serum neurofilament levels are associated with clinical measures of disease severity.

  • Antibiotic exposure and risk of Parkinson's disease in finland: A nationwide case‐control study
    Mov. Disord. (IF 8.061) Pub Date : 2019-11-18
    Tuomas H. Mertsalmi, Eero Pekkonen, Filip Scheperjans

    Gut microbiota alterations have been found in prodromal and established Parkinson's disease (PD). Antibiotic exposure can have long‐term effects on the composition of human intestinal microbiota, but a potential connection between antibiotic exposure and risk of PD has not been studied previously.

  • Distinct subthalamic coupling in the ON state describes motor performance in Parkinson's disease
    Mov. Disord. (IF 8.061) Pub Date : 2019-07-26
    Musa Ozturk, Aviva Abosch, David Francis, Jianping Wu, Joohi Jimenez‐Shahed, Nuri F. Ince

    Cross‐frequency coupling has been reported in the STN of patients with PD, but its significance and functional role are still not well understood. This study investigates pharmacological modulations of subthalamic oscillations and their nonlinear cross‐frequency interactions across three consecutive cycles over unique 24‐hour‐long recordings.

  • Immunomodulatory drugs alleviate l‐dopa‐induced dyskinesia in a rat model of Parkinson's disease
    Mov. Disord. (IF 8.061) Pub Date : 2019-07-23
    Laura Boi, Augusta Pisanu, Nigel H. Greig, Michael T. Scerba, David Tweedie, Giovanna Mulas, Sandro Fenu, Ezio Carboni, Saturnino Spiga, Anna R. Carta

    Thalidomide and closely related analogues are used clinically for their immunomodulatory and antiangiogenic properties mediated by the inhibition of the proinflammatory cytokine tumor necrosis factor α. Neuroinflammation and angiogenesis contribute to classical neuronal mechanisms underpinning the pathophysiology of l‐dopa‐induced dyskinesia, a motor complication associated with l‐dopa therapy in Parkinson's disease. The efficacy of thalidomide and the more potent derivative 3,6′‐dithiothalidomide on dyskinesia was tested in the 6‐hydroxydopamine Parkinson's disease model.

  • Magnetic Resonance Imaging–Visible Perivascular Spaces in Basal Ganglia Predict Cognitive Decline in Parkinson's Disease
    Mov. Disord. (IF 8.061) Pub Date : 2019-07-19
    Yae Won Park, Na‐Young Shin, Seok Jong Chung, Jiwoong Kim, Soo Mee Lim, Phil Hyu Lee, Seung‐Koo Lee, Kook Jin Ahn

    Growing evidence suggests an association between imaging biomarkers of small vessel disease and future cognitive decline in Parkinson's disease (PD). Recently, magnetic resonance imaging–visible perivascular space (PVS) has been considered as an imaging biomarker of small vessel disease, but its effect on cognitive decline in PD is yet to be investigated.

  • Early limbic microstructural alterations in apathy and depression in de novo Parkinson's disease
    Mov. Disord. (IF 8.061) Pub Date : 2019-07-15
    Stéphane Prange, Elise Metereau, Audrey Maillet, Eugénie Lhommée, Hélène Klinger, Pierre Pelissier, Danielle Ibarrola, Rolf A. Heckemann, Anna Castrioto, Léon Tremblay, Véronique Sgambato, Emmanuel Broussolle, Paul Krack, Stéphane Thobois

    Whether structural alterations underpin apathy and depression in de novo parkinsonian patients is unknown. The objectives of this study were to investigate whether apathy and depression in de novo parkinsonian patients are related to structural alterations and how structural abnormalities relate to serotonergic or dopaminergic dysfunction.

  • Young‐onset Parkinson's disease: Hospital utilization and medical comorbidity in a nationwide survey
    Mov. Disord. (IF 8.061) Pub Date : 2006-11-17
    Elan D. Louis, Claire Henchcliffe, Brian T. Bateman, H. Christian Schumacher

    Approximately 10% of Parkinson's disease (PD) patients have young‐onset PD (YOPD). From a public health perspective, YOPD is an important subgroup of PD patients, because they are expected to remain active users of the health care system for many decades. Health care utilization and medical comorbidity during hospitalization have not been assessed in these patients. The objectives of this study were to compare YOPD patients to control patients in terms of (1) hospital utilization and outcomes, and (2) medical comorbidities during hospitalization. The Nationwide Inpatient Sample (NIS) provides yearly data on hospital admissions and discharges from approximately 1,000 hospitals. NIS data sets (1998–2003) were used to identify persons 18 to 40 years of age, including 714 PD patients and 2,007 randomly selected control patients (1:3 ratio). Hospital length of stay (P < 0.001) and number of discharge diagnoses (P < 0.001) were higher in PD than control patients. PD patients were more likely than controls to be discharged to a short‐term hospital (odds ratio [OR], 2.23; 95% confidence interval [CI], 1.30–3.84; P = 0.004) or a skilled nursing facility (OR, 4.14; 95% CI, 3.06–5.61; P < 0.001); 20.4% required transfer to a short‐term hospital or another facility. The most common discharge diagnosis‐related group code in PD patients was psychosis (23% of patients), whereas pneumonia and hip or pelvic fractures were not associated with PD. YOPD patients had greater health care utilization and hospital morbidity than controls. Upon discharge, 1 in 5 required transfer to a short‐term hospital or another facility. Psychosis was the most common comorbidity, whereas several comorbidities associated with older PD patients (e.g., fractures) were not common. © 2006 Movement Disorder Society

  • The vicious cycle between α‐synuclein aggregation and autophagic‐lysosomal dysfunction
    Mov. Disord. (IF 8.061) Pub Date : 2019-11-15
    Giovanni Bellomo, Silvia Paciotti, Leonardo Gatticchi, Lucilla Parnetti

    The accumulation and misfolding of α‐synuclein (α‐syn) represent the main pathological hallmark of PD. Overexpression of α‐syn and failure of cellular protein degradation systems play a major role in α‐syn aggregation. The discovery of PD‐associated genes related to the autophagic‐lysosomal pathway, such as VPS35, LRRK2, GBA1, SMPD1, GALC, ASAH1, SCARB2, CTSD, CTSB, and GLA, confirms the involvement of cellular clearance systems dysfunction in PD pathogenesis. Of importance, lysosomal enzyme activity is altered both in genetic and sporadic PD. Decreased lysosomal enzymes activities were measured in the same brain regions where α‐syn accumulates, suggesting that a crosstalk between α‐syn aggregation and autophagic‐lysosomal impairment may exist. The understanding of autophagic‐lysosomal pathway dysfunctions’ role in the pathogenesis and progression of synucleinopathies opened new perspectives for novel possible therapeutic strategies. In this article, the evidences and mechanisms of the reciprocal relation between autophagic‐lysosomal pathway impairment and misfolded α‐syn aggregation and propagation are reviewed, together with the most promising compounds targeting autophagic‐lysosomal pathway restoration as a disease‐modifying strategy for PD treatment. © 2019 International Parkinson and Movement Disorder Society

  • HDQLIFE and Neuro‐QoL Physical Function Measures: Responsiveness in Persons With Huntington's Disease
    Mov. Disord. (IF 8.061) Pub Date : 2019-11-14
    Noelle E. Carlozzi, Nicholas R. Boileau, Kelvin L. Chou, Rebecca E. Ready, David Cella, Michael K. McCormack, Jennifer A. Miner, Praveen Dayalu

    Huntington's disease (HD) is a neurological disorder that causes severe motor symptoms that adversely impact health‐related quality of life. Patient‐reported physical function outcome measures in HD have shown cross‐sectional evidence of validity, but responsiveness has not yet been assessed.

  • Association Between Toll‐Like Receptor 4 (TLR4) and Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) Genetic Variants and Clinical Progression of Huntington's Disease
    Mov. Disord. (IF 8.061) Pub Date : 2019-11-14
    Romina Vuono, Antonina Kouli, Emilie M. Legault, Lauriane Chagnon, Kieren S. Allinson, Alberto La Spada, , Ida Biunno, Roger A. Barker, Janelle Drouin‐Ouellet

    Although Huntington's disease (HD) is caused by a single dominant gene, it is clear that there are genetic modifiers that may influence the age of onset and disease progression.

  • Temporal discrimination is altered in patients with isolated asymmetric and jerky upper limb tremor
    Mov. Disord. (IF 8.061) Pub Date : 2019-11-13
    Felix Gövert, Jos Becktepe, Bettina Balint, Lorenzo Rocchi, Florian Brugger, Alicia Garrido, Tim Walter, Ricci Hannah, John Rothwell, Rodger Elble, Günther Deuschl, Kailash Bhatia

    Unilateral or very asymmetric upper limb tremors with a jerky appearance are poorly investigated. Their clinical classification is an unsolved problem because their classification as essential tremor versus dystonic tremor is uncertain. To avoid misclassification as essential tremor or premature classification as dystonic tremor, the term indeterminate tremor was suggested.

  • Motor complications in Parkinson's disease: 13‐year follow‐up of the CamPaIGN cohort
    Mov. Disord. (IF 8.061) Pub Date : 2019-11-11
    Han‐Joon Kim, Sarah Mason, Thomas Foltynie, Sophie Winder‐Rhodes, Roger A. Barker, Caroline H. Williams‐Gray

    Long‐term population‐representative data on motor fluctuations and levodopa‐induced dyskinesias in Parkinson's disease is lacking.

  • Multimodal Magnetic Resonance Imaging Quantification of Brain Changes in Progressive Supranuclear Palsy
    Mov. Disord. (IF 8.061) Pub Date : 2019-11-11
    Nadya Pyatigorskaya, Lydia Yahia‐Cherif, Rahul Gaurav, Claire Ewenczyk, Cecile Gallea, Romain Valabregue, Fatma Gargouri, Benoit Magnin, Bertrand Degos, Emmanuel Roze, Eric Bardinet, Cyril Poupon, Isabelle Arnulf, Marie Vidailhet, Stéphane Lehericy

    Progressive supranuclear palsy (PSP) is a neurodegenerative clinically heterogeneous disorder, formal diagnosis being based on postmortem histological brain examination.

  • Functional inhibitory control dynamics in impulse control disorders in Parkinson's disease
    Mov. Disord. (IF 8.061) Pub Date : 2019-11-11
    Pedro M. Paz‐Alonso, I. Navalpotro‐Gomez, P. Boddy, R. Dacosta‐Aguayo, M. Delgado‐Alvarado, A. Quiroga‐Varela, H. Jimenez‐Urbieta, M. Carreiras, Maria C. Rodriguez‐Oroz

    Impulse control disorders related to alterations in the mesocorticolimbic dopamine network occur in Parkinson's disease (PD). Our objective was to investigate the functional neural substrates of reward processing and inhibitory control in these patients.

  • Retina thickness as a marker of neurodegeneration in prodromal lewy body disease
    Mov. Disord. (IF 8.061) Pub Date : 2019-11-11
    Jee‐Young Lee, Jeeyun Ahn, Sohee Oh, Joo Young Shin, Yu Kyeong Kim, Hyunwoo Nam, Beomseok Jeon

    We investigated retinal change and its relationship with neurodegeneration markers in a prodromal Parkinson cohort.

  • Multiple System Atrophy: Recent Developments and Future Perspectives
    Mov. Disord. (IF 8.061) Pub Date : 2019-11-06
    Wassilios G. Meissner, Pierre‐Olivier Fernagut, Benjamin Dehay, Patrice Péran, Anne Pavy‐Le Traon, Alexandra Foubert‐Samier, Miguel Lopez Cuina, Erwan Bezard, François Tison, Olivier Rascol

    Multiple system atrophy (MSA) is a rare and fatal neurodegenerative disorder characterized by a variable combination of parkinsonism, cerebellar impairment, and autonomic dysfunction. The pathologic hallmark is the accumulation of aggregated α‐synuclein in oligodendrocytes, forming glial cytoplasmic inclusions, which qualifies MSA as a synucleinopathy together with Parkinson's disease and dementia with Lewy bodies. The underlying pathogenesis is still not well understood. Some symptomatic treatments are available, whereas neuroprotection remains an urgent unmet treatment need. In this review, we critically appraise significant developments of the past decade with emphasis on pathogenesis, diagnosis, prognosis, and treatment development. We further discuss unsolved questions and highlight some perspectives. © 2019 International Parkinson and Movement Disorder Society

  • Blood biomarkers with Parkinson's disease clusters and prognosis: the oxford discovery cohort
    Mov. Disord. (IF 8.061) Pub Date : 2019-11-06
    Michael Lawton, Fahd Baig, Greg Toulson, Alireza Morovat, Samuel G. Evetts, Yoav Ben‐Shlomo, Michele T. Hu

    Predicting prognosis in Parkinson's disease (PD) has important implications for individual prognostication and clinical trials design and targeting novel treatments. Blood biomarkers could help in this endeavor.

  • Targeting the microglial NLRP3 inflammasome and its role in Parkinson's disease
    Mov. Disord. (IF 8.061) Pub Date : 2019-11-04
    Md. Ezazul Haque, Mahbuba Akther, Md. Jakaria, In‐Su Kim, Shofiul Azam, Dong‐Kug Choi

    Excessive activation of microglia and subsequent release of proinflammatory cytokines play a crucial role in neuroinflammation and neurodegeneration in Parkinson's disease (PD). Components of the nucleotide‐binding oligomerization domain and leucine‐rich‐repeat‐ and pyrin‐domain‐containing 3 inflammasome complex, leucine‐rich‐repeat‐ and pyrin‐domain‐containing 3, caspase‐1, and apoptosis‐associated speck‐like protein containing a CARD, are highly expressed in activated microglia in PD patient brains. Findings suggest that neurotoxins, aggregation of α‐synuclein, mitochondrial reactive oxygen species, and disrupted mitophagy are the key regulators of microglial leucine‐rich‐repeat‐ and pyrin‐domain‐containing 3 inflammasome activation and release of interleukin‐1β and interleukin‐18 caspase‐1‐mediated pyroptotic cell death in the substantia nigra of the brain. Although this evidence suggests the leucine‐rich‐repeat‐ and pyrin‐domain‐containing 3 inflammasome may be a potential drug target for treatment of PD, the exact mechanism of how the microglia sense these stimuli and initiate leucine‐rich‐repeat‐ and pyrin‐domain‐containing 3 inflammasome signaling is unknown. Here, the molecular mechanism and regulation of microglial leucine‐rich‐repeat‐ and pyrin‐domain‐containing 3 inflammasome activation and its role in the pathogenesis of PD are discussed. Moreover, the potential of both endogenous and synthetic leucine‐rich‐repeat‐ and pyrin‐domain‐containing 3 inflammasome modulators, long noncoding RNA, microRNA to develop novel therapeutics to treat PD is presented. Overall, we recommend that the microglial leucine‐rich‐repeat‐ and pyrin‐domain‐containing 3 inflammasome can be a potential target for PD treatment. © 2019 International Parkinson and Movement Disorder Society

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