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Parkinson Disease: HELP
Articles by Birgit Högl
Based on 30 articles published since 2010
(Why 30 articles?)
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Between 2010 and 2020, B. Högl wrote the following 30 articles about Parkinson Disease.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Editorial Sleep apnea in Parkinson's disease: when is it significant? 2010

Högl, Birgit. · ·Sleep Med · Pubmed #20133190.

ABSTRACT: -- No abstract --

2 Review Precision Medicine in Rapid Eye Movement Sleep Behavior Disorder. 2019

Högl, Birgit / Santamaria, Joan / Iranzo, Alex / Stefani, Ambra. ·Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, Innsbruck 6020, Austria. · Neurology Service, Multidisciplinary Sleep Unit, Hospital Clinic de Barcelona, Institut D'Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigacion Biomedica en Red de Enfermedades Neurodegenerativas, Calle Villarroel, 170, Barcelona 08036, Spain. · Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, Innsbruck 6020, Austria. Electronic address: ambra.stefani@i-med.ac.at. ·Sleep Med Clin · Pubmed #31375203.

ABSTRACT: In recent years, the diagnostic approach to rapid eye movement (REM) sleep behavior disorder (RBD) has become more objective and accurate. This was achieved mainly by introduction of methods to exactly quantify electromyographic (EMG) activity in various muscles during REM sleep. The most established muscle combination for RBD diagnosis is the mentalis and upper extremity EMG. Computer-assisted systems for this analysis have been described, and an increasing number of studies looked into analysis of video events. Recently, prodromal phases of isolated RBD have been recognized.

3 Review Restless legs syndrome and periodic leg movements in patients with movement disorders: Specific considerations. 2017

Högl, Birgit / Stefani, Ambra. ·Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. ·Mov Disord · Pubmed #28186669.

ABSTRACT: Restless legs syndrome is a frequent neurological disorder with potentially serious and highly distressing treatment complications. The role and potential implications of periodic leg movements during sleep range from being a genetic risk marker for restless legs syndrome to being a cardiovascular risk factor. The diagnosis of restless legs syndrome in patients with daytime movement disorders is challenging and restless legs syndrome needs to be differentiated from other sleep-related movement disorders. This article provides an update on the diagnosis of restless legs syndrome as an independent disorder and the role of periodic leg movements and reviews the association of restless legs syndrome with Parkinson's disease and other movement disorders. © 2017 International Parkinson and Movement Disorder Society.

4 Review Optimizing odor identification testing as quick and accurate diagnostic tool for Parkinson's disease. 2016

Mahlknecht, Philipp / Pechlaner, Raimund / Boesveldt, Sanne / Volc, Dieter / Pinter, Bernardette / Reiter, Eva / Müller, Christoph / Krismer, Florian / Berendse, Henk W / van Hilten, Jacobus J / Wuschitz, Albert / Schimetta, Wolfgang / Högl, Birgit / Djamshidian, Atbin / Nocker, Michael / Göbel, Georg / Gasperi, Arno / Kiechl, Stefan / Willeit, Johann / Poewe, Werner / Seppi, Klaus. ·Department of Neurology, Medical University Innsbruck, Innsbruck, Austria. · Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London, United Kingdom. · Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands. · Divisions of Human Nutrition, Wageningen University, Wageningen, The Netherlands. · Study Center Confraternitaet-PKJ Vienna, Vienna, Austria. · Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands. · Department of Applied Systems Research and Statistics, Johannes Kepler University Linz, Linz, Austria. · Department of Medical Statistics, Informatics and Health Economics, Medical University Innsbruck, Innsbruck, Austria. · Department of Neurology, Hospital of Bruneck, Bruneck, Italy. · Department of Neurology, Medical University Innsbruck, Innsbruck, Austria. klaus.seppi@uki.at. ·Mov Disord · Pubmed #27159493.

ABSTRACT: INTRODUCTION: The aim of this study was to evaluate odor identification testing as a quick, cheap, and reliable tool to identify PD. METHODS: Odor identification with the 16-item Sniffin' Sticks test (SS-16) was assessed in a total of 646 PD patients and 606 controls from three European centers (A, B, and C), as well as 75 patients with atypical parkinsonism or essential tremor and in a prospective cohort of 24 patients with idiopathic rapid eye movement sleep behavior disorder (center A). Reduced odor sets most discriminative for PD were determined in a discovery cohort derived from a random split of PD patients and controls from center A using L1-regularized logistic regression. Diagnostic accuracy was assessed in the rest of the patients/controls as validation cohorts. RESULTS: Olfactory performance was lower in PD patients compared with controls and non-PD patients in all cohorts (each P < 0.001). Both the full SS-16 and a subscore of the top eight discriminating odors (SS-8) were associated with an excellent discrimination of PD from controls (areas under the curve ≥0.90; sensitivities ≥83.3%; specificities ≥82.0%) and from non-PD patients (areas under the curve ≥0.91; sensitivities ≥84.1%; specificities ≥84.0%) in all cohorts. This remained unchanged when patients with >3 years of disease duration were excluded from analysis. All 8 incident PD cases among patients with idiopathic rapid eye movement sleep behavior disorder were predicted with the SS-16 and the SS-8 (sensitivity, 100%; positive predictive value, 61.5%). CONCLUSIONS: Odor identification testing provides excellent diagnostic accuracy in the distinction of PD patients from controls and diagnostic mimics. A reduced set of eight odors could be used as a quick tool in the workup of patients presenting with parkinsonism and for PD risk indication. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

5 Review Scales to assess sleep impairment in Parkinson's disease: critique and recommendations. 2010

Högl, Birgit / Arnulf, Isabelle / Comella, Cynthia / Ferreira, Joaquim / Iranzo, Alex / Tilley, Barbara / Trenkwalder, Claudia / Poewe, Werner / Rascol, Olivier / Sampaio, Cristina / Stebbins, Glenn T / Schrag, Anette / Goetz, Christopher G. ·Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. birgit.ho@i-med.ac.at ·Mov Disord · Pubmed #20931631.

ABSTRACT: There is a broad spectrum of sleep disturbances observed in Parkinson's disease (PD). A variety of scales have been applied to the evaluation of PD sleep and wakefulness, but only a small number have been assessed specifically for clinimetric properties in the PD population. The movement disorder society has commissioned this task force to examine these scales and to assess their use in PD. A systematic literature review was conducted to explore the use of sleep scales in PD and to determine which scales qualified for a detailed critique. The task force members, all of whom have extensive experience in assessing sleep in PD reviewed each of the scales using a structured proforma. Scales were categorized into recommended, suggested and listed according to predefined criteria. A total of 48 potential scales were identified from the search and reviewed. Twenty-nine were excluded because they did not meet review criteria or were variations of scales already included, leaving 19 scales that were critiqued and rated by the task force based on the rating criteria. Only six were found to meet criteria for recommendation or suggestion by the task force: the PD sleep scale (PDSS) and the Pittsburgh sleep quality index (PSQI) are recommended for rating overall sleep problems to screen and to measure severity, the SCOPA-sleep (SCOPA) is recommended for rating overall sleep problems both to screen and to measure severity, and for rating daytime sleepiness; the Epworth sleepiness scale (ESS) is recommended for rating daytime sleepiness to screen and to measure severity; the inappropriate sleep composite score (ISCS) is suggested for rating severe daytime sleepiness or sleep attacks to screen and to measure severity; and the Stanford sleepiness scale (SSS) is suggested for rating sleepiness and to measure severity at a specific moment. The task force does not recommend the development of new scales, but emphasizes the need for educational efforts to train physicians in sleep interview techniques and polysomnography.

6 Clinical Trial Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: a multicentre study. 2019

Postuma, Ronald B / Iranzo, Alex / Hu, Michele / Högl, Birgit / Boeve, Bradley F / Manni, Raffaele / Oertel, Wolfgang H / Arnulf, Isabelle / Ferini-Strambi, Luigi / Puligheddu, Monica / Antelmi, Elena / Cochen De Cock, Valerie / Arnaldi, Dario / Mollenhauer, Brit / Videnovic, Aleksandar / Sonka, Karel / Jung, Ki-Young / Kunz, Dieter / Dauvilliers, Yves / Provini, Federica / Lewis, Simon J / Buskova, Jitka / Pavlova, Milena / Heidbreder, Anna / Montplaisir, Jacques Y / Santamaria, Joan / Barber, Thomas R / Stefani, Ambra / St Louis, Erik K / Terzaghi, Michele / Janzen, Annette / Leu-Semenescu, Smandra / Plazzi, Guiseppe / Nobili, Flavio / Sixel-Doering, Friederike / Dusek, Petr / Bes, Frederik / Cortelli, Pietro / Ehgoetz Martens, Kaylena / Gagnon, Jean-Francois / Gaig, Carles / Zucconi, Marco / Trenkwalder, Claudia / Gan-Or, Ziv / Lo, Christine / Rolinski, Michal / Mahlknecht, Philip / Holzknecht, Evi / Boeve, Angel R / Teigen, Luke N / Toscano, Gianpaolo / Mayer, Geert / Morbelli, Silvia / Dawson, Benjamin / Pelletier, Amelie. ·Department of Neurology, McGill University, Montreal General Hospital, Montreal, Canada. · Centre d'Études Avancées en Médecine du Sommeil, Hôpital du Sacré-Cœur de Montréal, Montréal, Canada. · Neurology Service, Hospital Clinic de Barcelona, IDIBAPS, CIBERNED, Barcelona, Spain. · Oxford Parkinson's Disease Centre (OPDC) and Oxford University, Oxford, UK. · Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. · Mayo Clinic, Rochester, MN, USA. · Unit of Sleep Medicine and Epilepsy, IRCCS, C.Mondino Foundation, Pavia, Italy. · Department of Neurology, Philipps-Universität, Marburg, Germany. · Sleep disorders unit, Pitie-Salpetriere Hospital, IHU@ICM and Sorbonne University, Paris, France. · Sleep Disorders Center, Department of Neurology, Scientific Institute Ospedale San Raffaele, Vita-Salute University, Milan, Italy. · Sleep Center, Department of Cardiovascular and Neurological Sciences, University of Cagliari, Italy. · Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy. · IRCCS Institute of the Neurological Sciences, Ospedale Bellaria, ASL di Bologna, Bologna, Italy. · Sleep and Neurology Unit, Beau Soleil Clinic, Montpellier, France; EuroMov, University of Montpellier, Montpellier, France. · Clinical Neurology, Dept. of Neuroscience (DINOGMI), University of Genoa, and Polyclinic San Martino Hospital, Genoa, Italy. · Department of Neurosurgery (C.T.) University Medical Center, Göttingen; Paracelsus-Elena-Klinik (B.M., C.T. F. S-D.), Kassel, Germany. · Movement Disorders Unit and Division of Sleep Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, USA. · Department of Neurology and Centre of Clinical Neurosciences of the First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic. · Neuroscience Research Institute, Seoul National University College of Medicine, Department of Neurology, Seoul National University Hospital, Seoul, Korea. · Institute of Physiology Charité-Universitätsmedizin Berlin. Germany. · Sleep Unit, Department of Neurology, Hôpital Gui de Chauliac, Montpellier, INSERM U1061, Montpellier, F-34093 Cedex 5 France. · Department of Biomedical and Neuromotor Sciences, Bellaria Hospital, University of Bologna, Bologna, Italy. · IRCCS Institute of Neurological Sciences of Bologna, Bellaria Hospital, Bologna, Italy. · Brain and Mind Centre University of Sydney, Camperdown, Australia. · National Institute of Mental Health, Klecany, Third Faculty of Medicine, Charles Unviersity, Prague, Czech Republic. · Department of Neurology, Brigham and Women's Hospital, Boston; Harvard Medical School, Boston, USA. · Institute for Sleep Medicine and Neuromuscular Disorders, University Hospital Muenster, Muenster, Germany. · Department of Psychology, Université du Québec à Montréal, Montreal, Quebec, Canada. · Department of Human Genetics, McGill University, Montreal, Canada. · Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Canada. · Department of Neurology, Hephata Klinik, Schwalmstadt-Treysa, Germany. · Nuclear Medicine, Department of Health Sciences (DISSAL), University of Genoa and Polyclinic San Martino Hospital, Genoa, Italy. ·Brain · Pubmed #30789229.

ABSTRACT: Idiopathic REM sleep behaviour disorder (iRBD) is a powerful early sign of Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. This provides an unprecedented opportunity to directly observe prodromal neurodegenerative states, and potentially intervene with neuroprotective therapy. For future neuroprotective trials, it is essential to accurately estimate phenoconversion rate and identify potential predictors of phenoconversion. This study assessed the neurodegenerative disease risk and predictors of neurodegeneration in a large multicentre cohort of iRBD. We combined prospective follow-up data from 24 centres of the International RBD Study Group. At baseline, patients with polysomnographically-confirmed iRBD without parkinsonism or dementia underwent sleep, motor, cognitive, autonomic and special sensory testing. Patients were then prospectively followed, during which risk of dementia and parkinsonsim were assessed. The risk of dementia and parkinsonism was estimated with Kaplan-Meier analysis. Predictors of phenoconversion were assessed with Cox proportional hazards analysis, adjusting for age, sex, and centre. Sample size estimates for disease-modifying trials were calculated using a time-to-event analysis. Overall, 1280 patients were recruited. The average age was 66.3 ± 8.4 and 82.5% were male. Average follow-up was 4.6 years (range = 1-19 years). The overall conversion rate from iRBD to an overt neurodegenerative syndrome was 6.3% per year, with 73.5% converting after 12-year follow-up. The rate of phenoconversion was significantly increased with abnormal quantitative motor testing [hazard ratio (HR) = 3.16], objective motor examination (HR = 3.03), olfactory deficit (HR = 2.62), mild cognitive impairment (HR = 1.91-2.37), erectile dysfunction (HR = 2.13), motor symptoms (HR = 2.11), an abnormal DAT scan (HR = 1.98), colour vision abnormalities (HR = 1.69), constipation (HR = 1.67), REM atonia loss (HR = 1.54), and age (HR = 1.54). There was no significant predictive value of sex, daytime somnolence, insomnia, restless legs syndrome, sleep apnoea, urinary dysfunction, orthostatic symptoms, depression, anxiety, or hyperechogenicity on substantia nigra ultrasound. Among predictive markers, only cognitive variables were different at baseline between those converting to primary dementia versus parkinsonism. Sample size estimates for definitive neuroprotective trials ranged from 142 to 366 patients per arm. This large multicentre study documents the high phenoconversion rate from iRBD to an overt neurodegenerative syndrome. Our findings provide estimates of the relative predictive value of prodromal markers, which can be used to stratify patients for neuroprotective trials.

7 Article Full sequencing and haplotype analysis of MAPT in Parkinson's disease and rapid eye movement sleep behavior disorder. 2018

Li, Jiao / Ruskey, Jennifer A / Arnulf, Isabelle / Dauvilliers, Yves / Hu, Michele T M / Högl, Birgit / Leblond, Claire S / Zhou, Sirui / Ambalavanan, Amirthagowri / Ross, Jay P / Bourassa, Cynthia V / Spiegelman, Dan / Laurent, Sandra B / Stefani, Ambra / Charley Monaca, Christelle / Cochen De Cock, Valérie / Boivin, Michel / Ferini-Strambi, Luigi / Plazzi, Giuseppe / Antelmi, Elena / Young, Peter / Heidbreder, Anna / Labbe, Catherine / Ferman, Tanis J / Dion, Patrick A / Fan, Dongsheng / Desautels, Alex / Gagnon, Jean-François / Dupré, Nicolas / Fon, Edward A / Montplaisir, Jacques Y / Boeve, Bradley F / Postuma, Ronald B / Rouleau, Guy A / Ross, Owen A / Gan-Or, Ziv. ·Department of Neurology, Peking University Third Hospital, Beijing, China. · Montreal Neurological Institute, McGill University, Montréal, QC, Canada. · Department of Neurology and neurosurgery, McGill University, Montréal, QC, Canada. · Sleep Disorders Unit, Pitié Salpêtrière Hospital, Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière and Sorbonne Universities, UPMC Paris 6 univ, Paris, France. · Sleep Unit, National Reference Network for Narcolepsy, Department of Neurology Hôpital-Gui-de Chauliac, CHU Montpellier, INSERM U1061, Montpellier, France. · Oxford Parkinson's Disease Centre (OPDC), University of Oxford, Oxford, United Kingdom. · Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom. · Sleep Disorders Clinic, Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. · Department of Human Genetics, McGill University, H3A 0G4, Montréal, QC, Canada. · University Lille north of France, Department of clinical neurophysiology and sleep center, CHU Lille, Lille, France. · Sleep and neurology unit, Beau Soleil Clinic, Montpellier, France. · EuroMov, University of Montpellier, Montpellier, France. · GRIP, École de psychologie, Université Laval, Québec city, QC, Canada. · Institute of Genetic, Neurobiological and Social Foundations of Child Development, Tomsk State University, Tomsk, Russia. · Department of Neurological Sciences, Università Vita-Salute San Raffaele, Milan, Italy. · Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum, University of Bologna, Bologna, Italy. · IRCCS, Institute of Neurological Sciences of Bologna, Bologna, Italy. · Department of Sleep Medicine and Neuromuscular Disorders, University of Muenster, Muenster, Germany. · Department of Psychiatry and Psychology, Mayo Clinic, Jacksonville, Florida, USA. · Centre d'Études Avancées en Médecine du Sommeil, Hôpital du Sacré-Cœur de Montréal, Montréal, QC, Canada. · Department of Neurosciences, Université de Montréal, Montréal, QC, Canada. · Département de psychologie, Université du Québec à Montréal, Montréal, QC, Canada. · Division of Neurosciences, CHU de Québec, Université Laval, Quebec City, QC, Canada. · Department of Medicine, Faculty of Medicine, Université Laval, Quebec City, QC, Canada. · Department of Psychiatry, Université de Montréal, Montréal, QC, Canada. · Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA. · Department of Neurology, Montreal General Hospital, Montréal, QC, Canada. · Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA. · Department of Clinical Genomics, Mayo Clinic, Jacksonville, Florida, USA. ·Mov Disord · Pubmed #29756641.

ABSTRACT: BACKGROUND: MAPT haplotypes are associated with PD, but their association with rapid eye movement sleep behavior disorder is unclear. OBJECTIVE: To study the role of MAPT variants in rapid eye movement sleep behavior disorder. METHODS: Two cohorts were included: (A) PD (n = 600), rapid eye movement sleep behavior disorder (n = 613) patients, and controls (n = 981); (B) dementia with Lewy bodies patients with rapid eye movement sleep behavior disorder (n = 271) and controls (n = 950). MAPT-associated variants and the entire coding sequence of MAPT were analyzed. Age-, sex-, and ethnicity-adjusted analyses were performed to examine the association between MAPT, PD, and rapid eye movement sleep behavior disorder. RESULTS: MAPT-H2 variants were associated with PD (odds ratios: 0.62-0.65; P = 0.010-0.019), but not with rapid eye movement sleep behavior disorder. In PD, the H1 haplotype odds ratio was 1.60 (95% confidence interval: 1.12-2.28; P = 0.009), and the H2 odds ratio was 0.68 (95% confidence interval: 0.48-0.96; P = 0.03). The H2/H1 haplotypes were not associated with rapid eye movement sleep behavior disorder. CONCLUSIONS: Our results confirm the protective effect of the MAPT-H2 haplotype in PD, and define its components. Furthermore, our results suggest that MAPT does not play a major role in rapid eye movement sleep behavior disorder, emphasizing different genetic background than in PD in this locus. © 2018 International Parkinson and Movement Disorder Society.

8 Article [Frequent neurological diseases associated with the restless legs syndrome]. 2018

Bartl, M / Winkelmann, J / Högl, B / Paulus, W / Trenkwalder, C. ·Klinik für Klinische Neurophysiologie, Universitätsmedizin Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Deutschland. michael.bartl@med.uni-goettingen.de. · Institut für Neurogenomik Helmholtz Zentrum München, 85764, Neuherberg, Deutschland. · Neurologische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, 81675, München, Deutschland. · Munich Cluster for Systems Neurology (SyNergy), München, Deutschland. · Universitätsklinik für Neurologie, Medizinische Universität Innsbruck, Anichstraße 35, 6020, Innsbruck, Österreich. · Klinik für Klinische Neurophysiologie, Universitätsmedizin Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Deutschland. · Zentrum für Parkinson-Syndrome und Bewegungsstörungen, Paracelsus-Elena Klinik, Klinikstr. 16, 34128, Kassel, Deutschland. · Klinik für Neurochirurgie, Universitätsmedizin Göttingen, Robert Koch Str. 40, 37075, Göttingen, Deutschland. ·Nervenarzt · Pubmed #29736677.

ABSTRACT: BACKGROUND: Restless legs syndrome (RLS) is a common neurological disease. Studies have shown that RLS is associated with a variety of medical and neurological disorders. OBJECTIVES: Using the example of three associated neurological diseases, the significance for everyday therapy decisions is assessed. MATERIAL AND METHODS: A systematic search was carried out in PubMed for all studies with the keyword "RLS" in combination with polyneuropathies (PNP), Parkinson's disease (PD) and multiple sclerosis (MS) and classified according to the methodology in high, medium or low study quality. RESULTS: Of 16 studies on RLS and MS, 10 were rated as "high". The high association frequency of RLS in MS between 13.3% and 65.1% (the variability possibly originates from different methods) prevents further statements about the prevalence. Within 30 studies on Parkinson's disease 17 were classified as having a high quality. In patients with Parkinson disease RLS occurs most frequently during therapy and is related to the duration of dopaminergic treatment. In patients with polyneuropathy, only 5 out of 24 studies were classified as being of high quality and an increased RLS prevalence was detected for acquired polyneuropathies with heterogeneous data for hereditary forms. CONCLUSION: There is an increased prevalence of association with RLS for the diseases discussed. This prevalence is possibly determined by the pathophysiology of these disorders. These diseases are possibly characterized by genetic predispositions as well, which can hopefully be classified more accurately in the future.

9 Article LRRK2 protective haplotype and full sequencing study in REM sleep behavior disorder. 2018

Ouled Amar Bencheikh, Bouchra / Ruskey, Jennifer A / Arnulf, Isabelle / Dauvilliers, Yves / Monaca, Christelle Charley / De Cock, Valérie Cochen / Gagnon, Jean-François / Spiegelman, Dan / Hu, Michele T M / Högl, Birgit / Stefani, Ambra / Ferini-Strambi, Luigi / Plazzi, Giuseppe / Antelmi, Elena / Young, Peter / Heidbreder, Anna / Mollenhauer, Brit / Sixel-Döring, Friederike / Trenkwalder, Claudia / Oertel, Wolfgang / Montplaisir, Jacques Y / Postuma, Ronald B / Rouleau, Guy A / Gan-Or, Ziv. ·Montreal Neurological Institute, McGill University, Montréal, QC, H3A 0G4, Canada; Centre de Recherche, Centre Hospitalier de l'Universite de Montreal, Montreal, QC H2X 0A9, Canada. · Montreal Neurological Institute, McGill University, Montréal, QC, H3A 0G4, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, QC, H3A 0G4, Canada, Canada. · Sleep Disorders Unit, Pitié Salpêtrière Hospital, Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière and Sorbonne Universities, UPMC Paris 6 Univ, Paris, 75013, France. · Sleep Unit, National Reference Network for Narcolepsy, Department of Neurology Hôpital-Gui-de Chauliac, CHU Montpellier, INSERM U1061, Montpellier, 34000, France. · University Lille North of France, Department of Clinical Neurophysiology and Sleep Center, CHU Lille, Lille, 59000, France. · Sleep and Neurology Unit, Beau Soleil Clinic, Montpellier, 34070, France; EuroMov, University of Montpellier, Montpellier, 34095, France. · Centre d'Études Avancées en Médecine du Sommeil, Hôpital du Sacré-Cœur de Montréal, Montréal, QC, H4J 1C5, Canada; Département de Psychologie, Université du Québec à Montréal, Montréal, QC, H2L 2C4, Canada. · Oxford Parkinson's Disease Centre (OPDC), University of Oxford, Oxford, OX1 2JD, United Kingdom; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX1 2JD, United Kingdom. · Sleep Disorders Clinic, Department of Neurology, Medical University of Innsbruck, Innsbruck, 6020, Austria. · Department of Neurological Sciences, Università Vita-Salute San Raffaele, Milan, 20132, Italy. · Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum, University of Bologna, Bologna, 40126, Italy; IRCCS, Institute of Neurological Sciences of Bologna, Bologna, 40139, Italy. · Department of Sleep Medicine and Neuromuscular Disorders, University of Muenster, 48149, Germany. · Paracelsus-Elena Clinic, Centre of Parkinsonism and Movement Disorders, Kassel, Germany. · Paracelsus-Elena Clinic, Centre of Parkinsonism and Movement Disorders, Kassel, Germany; University Medical Center Goettingen, Department of Neurology, 37075 Goettingen, Germany. · Department of Neurology, University Clinic, Philipps Universität Marburg, Marburg, Germany; Institute for Neurogenomics, Helmholtz Center for Health and Environment, Munich, Germany. · Centre d'Études Avancées en Médecine du Sommeil, Hôpital du Sacré-Cœur de Montréal, Montréal, QC, H4J 1C5, Canada; Department of Psychiatry, Université de Montréal, Montréal, QC, H3T 1J4, Canada. · Montreal Neurological Institute, McGill University, Montréal, QC, H3A 0G4, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, QC, H3A 0G4, Canada, Canada; Department of Neurology, Montreal General Hospital, Montréal, QC, H3G 1A4, Canada. · Montreal Neurological Institute, McGill University, Montréal, QC, H3A 0G4, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, QC, H3A 0G4, Canada, Canada; Department of Human Genetics, McGill University, H3A 0G4, Montréal, QC, Canada. · Montreal Neurological Institute, McGill University, Montréal, QC, H3A 0G4, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, QC, H3A 0G4, Canada, Canada; Department of Human Genetics, McGill University, H3A 0G4, Montréal, QC, Canada. Electronic address: ziv.gan-or@mcgill.ca. ·Parkinsonism Relat Disord · Pubmed #29576439.

ABSTRACT: BACKGROUND: Individuals with rapid eye movement (REM)-sleep behavior disorder (RBD) are likely to progress to synucleinopathies, mainly Parkinson's disease (PD), dementia with Lewy-bodies (DLB) and multiple system atrophy (MSA). The genetics of RBD only partially overlaps with PD and DLB, and the role of LRRK2 variants in risk for RBD is still not clear. METHODS: The full coding sequence, exon-intron boundaries and 5' and 3' untranslated regions of LRRK2 were sequenced using targeted next-generation sequencing. A total of 350 RBD patients and 869 controls were sequenced, and regression and burden models were used to examine the association between LRRK2 variants and RBD. RESULTS: No pathogenic mutations that are known to cause PD were identified in RBD patients. The p.N551K-p.R1398H-p.K1423K haplotype was associated with a reduced risk for RBD (OR = 0.66, 95% CI 0.44-0.98, p = 0.0055 for the tagging p.N551K substitution). A common variant, p.S1647T, was nominally associated with risk for RBD (OR = 1.28, 95% CI 1.05-1.56, p = 0.029). Burden analysis identified associations with domains and exons that were derived by the variants of the protective haplotype, and no burden of other rare variants was identified. CONCLUSIONS: Carriers of the LRRK2 p.N551K-p.R1398H-p.K1423K haplotype have a reduced risk for developing RBD, yet PD-causing mutations probably have minor or no role in RBD. Additional work is needed to confirm these results and to identify the mechanism associated with reduced risk for RBD.

10 Article Consistency of "Probable RBD" Diagnosis with the RBD Screening Questionnaire: A Follow-up Study. 2017

Stefani, Ambra / Mahlknecht, Philipp / Seppi, Klaus / Nocker, Michael / Mair, Katherina J / Hotter, Anna / Stockner, Heike / Willeit, Johann / Kiechl, Stefan / Rungger, Gregor / Gasperi, Arno / Poewe, Werner / Högl, Birgit. ·Department of Neurology Medical University of Innsbruck Innsbruck Austria. · Department of Neurology Hospital of Bruneck Bruneck Italy. ·Mov Disord Clin Pract · Pubmed #30363451.

ABSTRACT: Introduction: The aim of this study was to evaluate the consistency of "probable RBD" diagnosis with the RBD screening questionnaire (RBDSQ) assessed 2 years apart in a population-based study. Methods: Probable RBD was assessed by RBDSQ in 2008 and in 2010 in the Bruneck Study Cohort, with participants aged ≥60 years. Results: A total of 437 participants completed the RBDSQ in 2008 and 2010. There were 29 (6.6%) and 23 (5.3%) participants with probable RBD in 2008 and in 2010, respectively. Only eight (1.8%) screened positive on both occasions. RBDSQ values 2 years apart showed low correlation with each other (Spearman rank coefficient r = 0.348, Conclusions: We found low agreement between the two assessments. Possible explanations are the fluctuation of untreated RBD expression and the poor utility of the RBDSQ to detect RBD in the general population. Until further PSG validation of the RBDSQ in population-based studies, investigators must be aware of the inherent uncertainty of questionnaire-based RBD diagnosis.

11 Article Dopamine transporter imaging deficit predicts early transition to synucleinopathy in idiopathic rapid eye movement sleep behavior disorder. 2017

Iranzo, Alex / Santamaría, Joan / Valldeoriola, Francesc / Serradell, Monica / Salamero, Manel / Gaig, Carles / Niñerola-Baizán, Aida / Sánchez-Valle, Raquel / Lladó, Albert / De Marzi, Roberto / Stefani, Ambra / Seppi, Klaus / Pavia, Javier / Högl, Birgit / Poewe, Werner / Tolosa, Eduard / Lomeña, Francisco. ·Neurology Service, Hospital Clinic de Barcelona, IDIBAPS, CIBERNED, Barcelona, Spain. · Psychiatry Service, Hospital Clinic de Barcelona, Barcelona, Spain. · Biomedical Research Networking Center of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Barcelona, Spain. · Department of Neurology, Medical University Innsbruck, Austria. · Nuclear Medicine Service, Hospital Clinic Barcelona, IDIBAPS, Barcelona, Spain. ·Ann Neurol · Pubmed #28833467.

ABSTRACT: OBJECTIVE: To determine the usefulness of dopamine transporter (DAT) imaging to identify idiopathic rapid eye movement sleep behavior disorder (IRBD) patients at risk for short-term development of clinically defined synucleinopathy. METHODS: Eighty-seven patients with polysomnography-confirmed IRBD underwent RESULTS: Baseline DAT deficit was found in 51 (58.6%) patients. During follow-up, 25 (28.7%) subjects developed clinically defined synucleinopathy (Parkinson's disease in 11, dementia with Lewy bodies in 13, and multiple system atrophy in 1) with mean latency of 3.2 ± 1.9 years from imaging. Kaplan-Meier survival analysis showed increased risk of incident synucleinopathy in patients with abnormal DAT-SPECT than with normal DAT-SPECT (20% vs 6% at 3 years, 33% vs 18% at 5 years; log rank test, p = 0.006). Receiver operating characteristics curve revealed that reduction of FP-CIT uptake in putamen greater than 25% discriminated patients with DAT deficit who developed synucleinopathy from patients with DAT deficit that remained disease free after 3 years of follow-up. At 5-year follow-up, DAT-SPECT had 75% sensitivity, 51% specificity, 44% positive predictive value, 80% negative predictive value, and likelihood ratio 1.54 to predict synucleinopathy. INTERPRETATION: DAT-SPECT identifies IRBD patients at short-term risk for synucleinopathy. Decreased FP-CIT putamen uptake greater than 25% predicts synucleinopathy after 3 years' follow-up. These observations may be useful to select candidates for disease modification trials in IRBD. Ann Neurol 2017;82:419-428.

12 Article Characterization of patients with longstanding idiopathic REM sleep behavior disorder. 2017

Iranzo, Alex / Stefani, Ambra / Serradell, Monica / Martí, Maria Jose / Lomeña, Francisco / Mahlknecht, Philipp / Stockner, Heike / Gaig, Carles / Fernández-Arcos, Ana / Poewe, Werner / Tolosa, Eduard / Högl, Birgit / Santamaria, Joan / Anonymous7380909. ·From the Neurology Service (A.I., M.S., M.J.M., C.G., A.F.-A., E.T., J.S.) and Nuclear Medicine Service (F.L.), Hospital Clinic de Barcelona, IDIBAPS, CIBERNED, Spain · and Department of Neurology (A.S., P.M., H.S., W.P., B.H.), Medical University Innsbruck, Austria. ·Neurology · Pubmed #28615430.

ABSTRACT: OBJECTIVE: To evaluate the presence of prodromal markers of Parkinson disease (PD) in patients with longstanding idiopathic REM sleep behavior disorder (IRBD), a small subgroup of individuals with IRBD with long-term follow-up thought not to be at risk of developing PD. METHODS: Demographic, clinical, and neuroimaging markers of PD were evaluated in 20 patients with polysomnographic-confirmed longstanding IRBD and in 32 matched controls. RESULTS: Patients were 16 men and 4 women with mean age of 72.9 ± 8.6 years and mean follow-up from IRBD diagnosis of 12.1 ± 2.6 years. Patients more often had objective smell loss (35% vs 3.4%, CONCLUSIONS: Prodromal PD markers are common in individuals with longstanding IRBD, suggesting that they are affected by an underlying neurodegenerative process. This observation may be useful for the design of disease-modifying trials to prevent PD onset in IRBD.

13 Article Longitudinal assessment of excessive daytime sleepiness in early Parkinson's disease. 2017

Amara, Amy W / Chahine, Lama M / Caspell-Garcia, Chelsea / Long, Jeffrey D / Coffey, Christopher / Högl, Birgit / Videnovic, Aleksandar / Iranzo, Alex / Mayer, Geert / Foldvary-Schaefer, Nancy / Postuma, Ron / Oertel, Wolfgang / Lasch, Shirley / Marek, Ken / Simuni, Tanya / Anonymous7160907. ·Department of Neurology, The University of Alabama at Birmingham, Birmingham, Alabama, USA. · Department of Neurology, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. · Department of Biostatistics, The University of Iowa, Iowa City, Iowa, USA. · Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. · Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA. · Neurology Service, Hospital Clinic de Barcelona, IDIBAPS, CIBERNED, Barcelona, Spain. · Department of Neurology, Hephata-Klinik, Hephata Hessisches Diakoniezentrum, e.V., Schwalmstadt-Treysa, Germany. · Cleveland Clinic Neurological Institute, Cleveland, Ohio, USA. · Division of Neurology, McGill University, Montreal, Québec, Canada. · Department of Neurology, Philipps University, Marburg, Germany. · Charitable Hertie Foundation, Frankfurt, Germany. · Institute for Neurodegenerative Disorders, New Haven, Connecticut, USA. · Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. ·J Neurol Neurosurg Psychiatry · Pubmed #28554959.

ABSTRACT: BACKGROUND: Excessive daytime sleepiness (EDS) is common and disabling in Parkinson's disease (PD). Predictors of EDS are unclear, and data on biological correlates of EDS in PD are limited. We investigated clinical, imaging and biological variables associated with longitudinal changes in sleepiness in early PD. METHODS: The Parkinson's Progression Markers Initiative is a prospective cohort study evaluating progression markers in participants with PD who are unmedicated at baseline (n=423) and healthy controls (HC; n=196). EDS was measured with the Epworth Sleepiness Scale (ESS). Clinical, biological and imaging variables were assessed for associations with EDS for up to 3 years. A machine learning approach (random survival forests) was used to investigate baseline predictors of incident EDS. RESULTS: ESS increased in PD from baseline to year 3 (mean±SD 5.8±3.5 to 7.55±4.6, p<0.0001), with no change in HC. Longitudinally, EDS in PD was associated with non-tremor dominant phenotype, autonomic dysfunction, depression, anxiety and probable behaviour disorder, but not cognitive dysfunction or motor severity. Dopaminergic therapy was associated with EDS at years 2 and 3, as dose increased. EDS was also associated with presynaptic dopaminergic dysfunction, whereas biofluid markers at year 1 showed no significant associations with EDS. A predictive index for EDS was generated, which included seven baseline characteristics, including non-motor symptoms and cerebrospinal fluid phosphorylated-tau/total-tau ratio. CONCLUSIONS: In early PD, EDS increases significantly over time and is associated with several clinical variables. The influence of dopaminergic therapy on EDS is dose dependent. Further longitudinal analyses will better characterise associations with imaging and biomarkers.

14 Article Circadian Rhythms and Chronotherapeutics-Underappreciated Approach to Improving Sleep and Wakefulness in Parkinson Disease. 2017

Högl, Birgit. ·Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. ·JAMA Neurol · Pubmed #28241156.

ABSTRACT: -- No abstract --

15 Article The dementia-associated APOE ε4 allele is not associated with rapid eye movement sleep behavior disorder. 2017

Gan-Or, Ziv / Montplaisir, Jacques Y / Ross, Jay P / Poirier, Judes / Warby, Simon C / Arnulf, Isabelle / Strong, Stephanie / Dauvilliers, Yves / Leblond, Claire S / Hu, Michele T M / Högl, Birgit / Stefani, Ambra / Monaca, Christelle Charley / De Cock, Valérie Cochen / Boivin, Michel / Ferini-Strambi, Luigi / Plazzi, Giuseppe / Antelmi, Elena / Young, Peter / Heidbreder, Anna / Barber, Thomas R / Evetts, Samuel G / Rolinski, Michal / Dion, Patrick A / Desautels, Alex / Gagnon, Jean-François / Dupré, Nicolas / Postuma, Ronald B / Rouleau, Guy A. ·Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Human Genetics, McGill University, Montréal, Quebec, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, Quebec, Canada. Electronic address: ziv.gan-or@mail.mcgill.ca. · Centre d'Études Avancées en Médecine du Sommeil, Hôpital du Sacré-Cœur de Montréal, Montréal, Quebec, Canada; Department of Psychiatry, Université de Montréal, Montréal, Quebec, Canada. · Department of Human Genetics, McGill University, Montréal, Quebec, Canada. · Department of Psychiatry, McGill University, Montréal, Quebec, Canada; Douglas Mental Health University Institute, Montréal, Quebec, Canada. · Sleep Disorders Unit, Pitié Salpêtrière Hospital, Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière and Sorbonne Universities, UPMC Paris 6 univ, Paris, France. · Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada. · Sleep Unit, National Reference Network for Narcolepsy, Department of Neurology Hôpital-Gui-de Chauliac, CHU Montpellier, INSERM U1061, Montpellier, France. · Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Human Genetics, McGill University, Montréal, Quebec, Canada. · Oxford Parkinson's Disease Centre (OPDC), University of Oxford, Oxford, UK; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK. · Sleep Disorders Clinic, Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. · Department of Clinical Neurophysiology and Sleep Center, University Lille North of France, CHU Lille, Lille, France. · Sleep and Neurology Unit, Beau Soleil Clinic, Montpellier, France; EuroMov, University of Montpellier, Montpellier, France. · GRIP, École de psychologie, Université Laval, Québec city, Quebec, Canada; Institute of Genetic, Neurobiological and Social Foundations of Child Development, Tomsk State University, Tomsk, Russia. · Department of Neurological Sciences, Università Vita-Salute San Raffaele, Milan, Italy. · Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum, University of Bologna, Bologna, Italy; IRCCS, Institute of Neurological Sciences of Bologna, Bologna, Italy. · Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum, University of Bologna, Bologna, Italy. · Department of Sleep Medicine and Neuromuscular Disorders, University of Muenster, Germany. · Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, Quebec, Canada. · Centre d'Études Avancées en Médecine du Sommeil, Hôpital du Sacré-Cœur de Montréal, Montréal, Quebec, Canada; Department of Neurosciences, Université de Montréal, Montréal, Quebec, Canada. · Centre d'Études Avancées en Médecine du Sommeil, Hôpital du Sacré-Cœur de Montréal, Montréal, Quebec, Canada; Département de psychologie, Université du Québec à Montréal, Montréal, Quebec, Canada. · Faculté de Médecine, Université Laval, CHU de Québec (Enfant-Jésus), Québec, Quebec, Canada. · Department of Neurology and Neurosurgery, McGill University, Montréal, Quebec, Canada; Department of Neurology, Montreal General Hospital, Montréal, Quebec, Canada. · Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Human Genetics, McGill University, Montréal, Quebec, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, Quebec, Canada. ·Neurobiol Aging · Pubmed #27814994.

ABSTRACT: The present study aimed to examine whether the APOE ε4 allele, associated with dementia with Lewy bodies (DLB), and possibly with dementia in Parkinson's disease (PD), is also associated with idiopathic rapid eye movement sleep behavior disorder (RBD). Two single nucleotide polymorphisms, rs429358 and rs7412, were genotyped in RBD patients (n = 480) and in controls (n = 823). APOE ε4 allele frequency was 0.14 among RBD patients and 0.13 among controls (OR = 1.11, 95% CI: 0.88-1.40, p = 0.41). APOE ε4 allele frequencies were similar in those who converted to DLB (0.14) and those who converted to Parkinson's disease (0.12) or multiple system atrophy (0.14, p = 1.0). The APOE ε4 allele is neither a risk factor for RBD nor it is associated with conversion from RBD to DLB or other synucleinopathies.

16 Article The role of the melanoma gene MC1R in Parkinson disease and REM sleep behavior disorder. 2016

Gan-Or, Ziv / Mohsin, Noreen / Girard, Simon L / Montplaisir, Jacques Y / Ambalavanan, Amirthagowri / Strong, Stephanie / Mallett, Victoria / Laurent, Sandra B / Bourassa, Cynthia V / Boivin, Michel / Langlois, Melanie / Arnulf, Isabelle / Högl, Birgit / Frauscher, Birgit / Monaca, Christelle / Desautels, Alex / Gagnon, Jean-François / Postuma, Ronald B / Dion, Patrick A / Dauvilliers, Yves / Dupre, Nicolas / Alcalay, Roy N / Rouleau, Guy A. ·Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Human Genetics, McGill University, Montréal, Quebec, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, Quebec, Canada. Electronic address: ziv.gan-or@mail.mcgill.ca. · Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada. · Department of Human Genetics, McGill University, Montréal, Quebec, Canada. · Centre d'Études Avancées en Médecine du Sommeil, Hôpital du Sacré-Cœur de Montréal, Montréal, Quebec, Canada; Department of Psychiatry, Université de Montréal, Montréal, Quebec, Canada. · Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Human Genetics, McGill University, Montréal, Quebec, Canada. · GRIP, École de Psychologie, Université Laval, Québec City, Quebec, Canada; Institute of Genetics, Neurobiological and Social Foundations of Child Development, Tomsk State University, Tomsk, Russia. · Faculté de Médecine, Université Laval, CHU de Québec (Enfant-Jésus), Québec, Quebec, Canada. · Sleep Disorders Unit, Pitié Salpêtrière Hospital, Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière and Sorbonne Universities, UPMC Paris 6 univ, Paris, France. · Sleep Disorders Clinic, Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. · Department of Clinical Neurophysiology and Sleep Center, CHU Lille, University Lille North of France, Lille, France. · Centre d'Études Avancées en Médecine du Sommeil, Hôpital du Sacré-Cœur de Montréal, Montréal, Quebec, Canada; Department of Neurosciences, Université de Montréal, Montréal, Canada. · Centre d'Études Avancées en Médecine du Sommeil, Hôpital du Sacré-Cœur de Montréal, Montréal, Quebec, Canada; Département de Psychologie, Université du Québec à Montréal, Montréal, Quebec, Canada. · Department of Neurology, Montreal General Hospital, Montréal, Quebec, Canada. · Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, Quebec, Canada. · Sleep Unit, National Reference Network for Narcolepsy, Department of Neurology Hôpital-Gui-de Chauliac, CHU Montpellier, INSERM U1061, Montpellier, France. · Department of Neurology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA. · Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Human Genetics, McGill University, Montréal, Quebec, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, Quebec, Canada. Electronic address: guy.rouleau@mcgill.ca. ·Neurobiol Aging · Pubmed #27131830.

ABSTRACT: The MC1R gene, suggested to be involved in Parkinson disease (PD) and melanoma, was sequenced in PD patients (n = 539) and controls (n = 265) from New York, and PD patients (n = 551), rapid eye movement sleep behavior disorder (RBD) patients (n = 351), and controls (n = 956) of European ancestry. Sixty-eight MC1R variants were identified, including 7 common variants with frequency > 0.01. None of the common variants was associated with PD or RBD in the different regression models. In a meta-analysis with fixed-effect model, the p.R160W variant was associated with an increased risk for PD (odds ratio = 1.22, 95% confidence interval = 1.02-1.47, p = 0.03) but with significant heterogeneity (p = 0.048). Removing one study that introduced the heterogeneity resulted in nonsignificant association (odds ratio = 1.11, 95% confidence interval, 0.92-1.35, p = 0.27, heterogeneity p = 0.57). Rare variants had similar frequencies in patients and controls (10.54% and 10.15%, respectively, p = 0.75), and no cumulative effect of carrying more than one MC1R variant was found. The present study does not support a role for the MC1R p.R160W and other variants in susceptibility for PD or RBD.

17 Article Loss of dorsolateral nigral hyperintensity on 3.0 tesla susceptibility-weighted imaging in idiopathic rapid eye movement sleep behavior disorder. 2016

De Marzi, Roberto / Seppi, Klaus / Högl, Birgit / Müller, Christoph / Scherfler, Christoph / Stefani, Ambra / Iranzo, Alex / Tolosa, Eduardo / Santamarìa, Joan / Gizewski, Elke / Schocke, Michael / Skalla, Elisabeth / Kremser, Christian / Poewe, Werner. ·Department of Neurology, Medical University Innsbruck, Innsbruck, Austria. · Neuroimaging Research Core Facility, Medical University Innsbruck, Innsbruck, Austria. · Neurology Service, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERNED, Barcelona, Spain. · Department of Radiology, Medical University Innsbruck, Innsbruck, Austria. ·Ann Neurol · Pubmed #27016314.

ABSTRACT: We assessed loss of dorsolateral nigral hyperintensity (DNH) on high-field susceptibility-weighted imaging (SWI), a novel magnetic resonance imaging marker for Parkinson's disease (PD), in 15 subjects with idiopathic rapid eye movement sleep behavior disorder (iRBD) and compared findings to 42 healthy controls (HCs) and 104 PD patients. We found loss of DNH in at least two thirds of iRBD subjects, which approaches the rate observed in PD and is in contrast to findings in HCs. We propose that absence of DNH on high-field SWI could identify prodromal degenerative parkinsonism in iRBD. Ann Neurol 2016;79:1026-1030.

18 Article Probable RBD and association with neurodegenerative disease markers: A population-based study. 2015

Mahlknecht, Philipp / Seppi, Klaus / Frauscher, Birgit / Kiechl, Stefan / Willeit, Johann / Stockner, Heike / Djamshidian, Atbin / Nocker, Michael / Rastner, Verena / Defrancesco, Michaela / Rungger, Gregor / Gasperi, Arno / Poewe, Werner / Högl, Birgit. ·Department of Neurology, Medical University of Innsbruck, Austria. · Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London, UK. · Department of Molecular Neuroscience and Reta Lila Weston Institute for Neurological Studies, University of London, London, UK. · Department of Psychiatry, Medical University Innsbruck, Austria. · Department of Neurology, Hospital of Bruneck, Italy. ·Mov Disord · Pubmed #26208108.

ABSTRACT: BACKGROUND: The prevalence of rapid eye movement sleep behavior disorder (RBD) and its association with markers of neurodegeneration in the general population are poorly defined. METHODS: We assessed the prevalence of probable RBD defined by two validated questionnaires, the RBD Screening Questionnaire (RBDSQ) and the Innsbruck RBD-Inventory (RBD-I), and studied its associations with clinical and imaging markers for neurodegeneration in the Bruneck Study cohort aged 60 y or older. RESULTS: Of the 456 participants without Parkinson's disease, 4.6% (RBDSQ; 95%CI, 3.0%-7.0%) and 7.7% (RBD-I; 95%CI, 5.6%-10.5%) had probable RBD. Probable RBD diagnosed with either of the questionnaires was associated with hyposmia (trend; P < 0.1), anxiety (P < 0.05), depression (P < 0.05), antidepressant use (P < 0.05), and self-reported non-motor symptoms (P < 0.01), specifically, dribbling saliva, memory problems, apathy, concentration problems, and anxiety. CONCLUSIONS: Our findings may provide a basis for future studies intending to identify cohorts at risk for Lewy body diseases through screening of the general elderly population for RBD.

19 Article Correlates of excessive daytime sleepiness in de novo Parkinson's disease: A case control study. 2015

Simuni, Tanya / Caspell-Garcia, Chelsea / Coffey, Christopher / Chahine, Lama M / Lasch, Shirley / Oertel, Wolfgang H / Mayer, Geert / Högl, Birgit / Postuma, Ron / Videnovic, Aleksandar / Amara, Amy Willis / Marek, Ken / Anonymous7990833. ·Northwestern University Feinberg School of Medicine, Chicago, IL, USA. · The University of Iowa, Iowa City, IA, USA. · The University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. · Institute for Neurodegenerative Disorders, New Haven, CT, USA. · Charitable Hertie Foundation, Frankfurt/Main, Germany. · Hephata-Klinik, Hephata Hessisches Diakoniezentrum e. V. · Innsbruck Medical University, Innsbruck, Austria. · McGill University, Montréal, Québec, Canada. · Massachusetts General Hospital, Boston, MA, USA. · UAB School of Medicine, Birmingham, AL, USA. ·Mov Disord · Pubmed #26095202.

ABSTRACT: OBJECTIVE: This study was undertaken to determine the frequency and correlates of excessive daytime sleepiness in de novo, untreated Parkinson's disease (PD) patients compared with the matched healthy controls. METHODS: Data were obtained from the Parkinson's Progression Markers Initiative, an international study of de novo, untreated PD patients and healthy controls. At baseline, participants were assessed with a wide range of motor and nonmotor scales, including the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Excessive daytime sleepiness was assessed based on the Epworth Sleepiness scale (ESS), with a cutoff of 10. RESULTS: Four hundred twenty-three PD subjects and 196 healthy controls were recruited into the study. Mean ESS (min, max) score was 5.8 (0, 20) for the PD subjects and 5.6 (0, 19) for healthy controls (P = 0.54). Sixty-six (15.6%) PD subjects and 24 (12%) healthy controls had ESS of at least 10 (P = 0.28). No difference was seen in demographic characteristics, age of onset, disease duration, PD subtype, cognitive status, or utilization of sedatives between the PD sleepiness-positive versus the negative group. The sleepiness-positive group had higher MDS-UPDRS Part I and II but not III scores, and higher depression and autonomic dysfunction scores. Sleepiness was associated with a marginal reduction of A-beta (P = 0.05) but not alpha-synuclein spinal fluid levels in PD. CONCLUSIONS: This largest case control study demonstrates no difference in prevalence of excessive sleepiness in subjects with de novo untreated PD compared with healthy controls. The only clinical correlates of sleepiness were mood and autonomic dysfunction. Ongoing longitudinal analyses will be essential to further examine clinical and biological correlates of sleepiness in PD and specifically the role of dopaminergic therapy.

20 Article Parkinson's Disease Genetic Loci in Rapid Eye Movement Sleep Behavior Disorder. 2015

Gan-Or, Z / Girard, S L / Noreau, A / Leblond, C S / Gagnon, J F / Arnulf, I / Mirarchi, C / Dauvilliers, Y / Desautels, A / Mitterling, T / Cochen De Cock, V / Frauscher, B / Monaca, C / Hogl, B / Dion, P A / Postuma, R B / Montplaisir, J Y / Rouleau, G A. ·Montreal Neurological Institute and McGill University, Montréal, QC, Canada. ·J Mol Neurosci · Pubmed #25929833.

ABSTRACT: Rapid eye movement (REM) sleep behavior disorder (RBD) is a prodromal condition for Parkinson's disease (PD) and other synucleinopathies, which often occurs many years before the onset of PD. We analyzed 261 RBD patients and 379 controls for nine PD-associated SNPs and examined their effects, first upon on RBD risk and second, on eventual progression to synucleinopathies in a prospective follow-up in a subset of patients. The SCARB2 rs6812193 (OR = 0.67, 95 % CI = 0.51-0.88, p = 0.004) and the MAPT rs12185268 (OR-0.43, 95 % CI-0.26-0.72, p = 0.001) were associated with RBD in different models. Kaplan-Meier survival analysis in a subset of RBD patients (n = 56), demonstrated that homozygous carriers of the USP25 rs2823357 SNP had progressed to synucleinopathies faster than others (log-rank p = 0.003, Breslow p = 0.005, Tarone-Ware p = 0.004). As a proof-of-concept study, these results suggest that RBD may be associated with at least a subset of PD-associated genes, and demonstrate that combining genetic and prodromal clinical data may help identifying individuals that are either more or less susceptible to develop synucleinopathies. More studies are necessary to replicate these results, and identify more genetic factors affecting progression from RBD to synucleinopathies.

21 Article Dreaming furiously? A sleep laboratory study on the dream content of people with Parkinson's disease and with or without rapid eye movement sleep behavior disorder. 2015

Valli, Katja / Frauscher, Birgit / Peltomaa, Taina / Gschliesser, Viola / Revonsuo, Antti / Högl, Birgit. ·Centre for Cognitive Neuroscience, Turku Brain and Mind Center, Department of Psychology, University of Turku, Turku, Finland; School of Bioscience, University of Skövde, Skövde, Sweden. Electronic address: katval@utu.fi. · Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. · Centre for Cognitive Neuroscience, Turku Brain and Mind Center, Department of Psychology, University of Turku, Turku, Finland. · Centre for Cognitive Neuroscience, Turku Brain and Mind Center, Department of Psychology, University of Turku, Turku, Finland; School of Bioscience, University of Skövde, Skövde, Sweden. ·Sleep Med · Pubmed #25683562.

ABSTRACT: OBJECTIVE: Rapid eye movement (REM) sleep behavior disorder (RBD) has been related to altered, action-filled, vivid, and aggressive dream content, but research comparing the possible differences in dreams of Parkinson's disease (PD) patients with and without RBD is scarce. The dream content of PD patients with and without RBD was analyzed with specific focus on action-filledness, vividness, emotional valence, and threats. METHODS: A total of 69 REM and NREM dream reports were collected in the sleep laboratory, 37 from nine PD patients with RBD and 32 from six PD patients without RBD. A content analysis of (1) action-filledness (actions and environmental events); (2) vividness (emotions and cognitive activity); (3) intensity of actions, events and emotions; (4) emotional valence, and (5) threatening events was performed on the transcripts. RESULTS: Altogether 563 dream elements expressing action-filledness and vividness were found. There were no significant between-group differences in the number or distribution of elements reflecting action-filledness or vividness, emotional valence or threats. In within-group analyses, PD patients with RBD had significantly more negative compared to positive dreams (p = 0.012) and compared to PD patients without RBD, a tendency to have more intense actions in their dreams (p = 0.066). CONCLUSIONS: Based on the results of this study, there are no major between-group differences in the action-filledness, vividness, or threat content of dreams of PD patients with and without RBD. However, within-group analyses revealed that dreams were more often negatively than positively toned in PD patients with RBD.

22 Article Diagnostic value of the REM sleep behavior disorder screening questionnaire in Parkinson's disease. 2015

Stiasny-Kolster, Karin / Sixel-Döring, Friederike / Trenkwalder, Claudia / Heinzel-Gutenbrunner, Monika / Seppi, Klaus / Poewe, Werner / Högl, Birgit / Frauscher, Birgit. ·Somnomar, Institute for Medical Research and Sleep Medicine, Marburg, Germany; Philipps-University, Marburg, Germany. · Paracelsus-Elena Klinik, Kassel, Germany. · Paracelsus-Elena Klinik, Kassel, Germany; University of Goettingen, Goettingen, Germany. · Department of Child and Adolescent Psychiatry and Psychotherapy, Philipps-University, Marburg, Germany. · Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. · Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. Electronic address: birgit.frauscher@i-med.ac.at. ·Sleep Med · Pubmed #25534709.

ABSTRACT: OBJECTIVE: We aimed to validate the rapid eye movement (REM) sleep behavior disorder (RBD) screening questionnaire (RBDSQ) in 2 independent samples of patients with Parkinson's disease (PD) using different settings when performing the investigations. METHODS: The RBDSQ was administered to two independent samples of 52 and 75 consecutive PD patients investigated with video-polysomnography (vPSG). RESULTS: In sample A, the RBDSQ identified 46/52 (88.5%) patients correctly. In sample B, 50/75 (66.7%) patients were identified correctly. Considering a cut-off score of ≥ 5 as a positive test result, sample A showed a sensitivity of 0.90 and a specificity of 0.87, sample B showed a sensitivity of 0.68 and a specificity of 0.63. Main differences between both groups were that patients of sample A underwent a sleep history including RBD assessment prior to administration of the RBDSQ, whereas in sample B the RBDSQ was administered during routine work-up. CONCLUSIONS: The diagnostic value of the RBDSQ strongly depends on the clinical setting and may be influenced by the individual's awareness on RBD. This finding is a critical issue which deserves clarification before use of this and other questionnaires can be recommended in epidemiological studies.

23 Article Five-year follow-up of substantia nigra echogenicity in idiopathic REM sleep behavior disorder. 2014

Iranzo, Alex / Stockner, Heike / Serradell, Mónica / Seppi, Klaus / Valldeoriola, Francesc / Frauscher, Birgit / Molinuevo, José Luis / Vilaseca, Isabel / Mitterling, Thomas / Gaig, Carles / Vilas, Dolores / Santamaria, Joan / Högl, Birgit / Tolosa, Eduard / Poewe, Werner. ·Neurology Service, Hospital Clinic de Barcelona, IDIBAPS, CIBERNED, Barcelona, Spain. ·Mov Disord · Pubmed #25384461.

ABSTRACT: Hyperechogenicity of the substantia nigra visualized by transcranial sonography occurs in most Parkinson's disease (PD) patients. Idiopathic rapid eye movement (REM) sleep behavior disorder (IRBD) subjects eventually develop PD and other synucleinopathies. This study was undertaken to evaluate whether in IRBD, transcranial sonography identifies subjects who convert to PD and other synucleinopathies, and whether substantia nigra echogenic size changes with time. It was a prospective study in which 55 IRBD patients underwent transcranial sonography at baseline and were invited to follow-up after 5 years. Patients were assessed by the same experienced sonographer who was blinded to clinical data and baseline transcranial sonography results, and used the same equipment and adjustments. Twenty-one (38.2%) subjects were diagnosed with a synucleinopathy (PD in 11, dementia with Lewy bodies in nine, and multiple system atrophy in one). Sensitivity of baseline substantia nigra hyperechogenicity for the development of a synucleinopathy was 42.1%, specificity 67.7%, positive predictive value 44.4%, negative predictive value 65.6%, and relative risk 1.29. No differences were detected between the first and second examination in mean size of the substantia nigra (0.20 ± 0.09 cm(2) vs. 0.19 ± 0.07 cm(2) ; P = 0.777) and in percentage of patients with substantia nigra hyperechogenicity (33.3% vs. 42.8%, P = 0.125). Transcranial sonography of the substantia nigra alone is not a useful tool to identify IRBD subjects at risk for the development of PD or a synucleinopathy after 5 years of follow-up. In IRBD, transcranial sonography cannot be used to monitor the degenerative process in the substantia nigra, because echogenicity size remains stable over time.

24 Article Rapid eye movement sleep behavior disorder: devising controlled active treatment studies for symptomatic and neuroprotective therapy--a consensus statement from the International Rapid Eye Movement Sleep Behavior Disorder Study Group. 2013

Schenck, C H / Montplaisir, J Y / Frauscher, B / Hogl, B / Gagnon, J-F / Postuma, R / Sonka, K / Jennum, P / Partinen, M / Arnulf, I / Cochen de Cock, V / Dauvilliers, Y / Luppi, P-H / Heidbreder, A / Mayer, G / Sixel-Döring, F / Trenkwalder, C / Unger, M / Young, P / Wing, Y K / Ferini-Strambi, L / Ferri, R / Plazzi, G / Zucconi, M / Inoue, Y / Iranzo, A / Santamaria, J / Bassetti, C / Möller, J C / Boeve, B F / Lai, Y Y / Pavlova, M / Saper, C / Schmidt, P / Siegel, J M / Singer, C / St Louis, E / Videnovic, A / Oertel, W. ·Minnesota Regional Sleep Disorders Center, Department of Psychiatry, Hennepin County Medical Center and University of Minnesota Medical School, Minneapolis, MN, USA. schen010@umn.edu ·Sleep Med · Pubmed #23886593.

ABSTRACT: OBJECTIVES: We aimed to provide a consensus statement by the International Rapid Eye Movement Sleep Behavior Disorder Study Group (IRBD-SG) on devising controlled active treatment studies in rapid eye movement sleep behavior disorder (RBD) and devising studies of neuroprotection against Parkinson disease (PD) and related neurodegeneration in RBD. METHODS: The consensus statement was generated during the fourth IRBD-SG symposium in Marburg, Germany in 2011. The IRBD-SG identified essential methodologic components for a randomized trial in RBD, including potential screening and diagnostic criteria, inclusion and exclusion criteria, primary and secondary outcomes for symptomatic therapy trials (particularly for melatonin and clonazepam), and potential primary and secondary outcomes for eventual trials with disease-modifying and neuroprotective agents. The latter trials are considered urgent, given the high conversion rate from idiopathic RBD (iRBD) to Parkinsonian disorders (i.e., PD, dementia with Lewy bodies [DLB], multiple system atrophy [MSA]). RESULTS: Six inclusion criteria were identified for symptomatic therapy and neuroprotective trials: (1) diagnosis of RBD needs to satisfy the International Classification of Sleep Disorders, second edition, (ICSD-2) criteria; (2) minimum frequency of RBD episodes should preferably be ⩾2 times weekly to allow for assessment of change; (3) if the PD-RBD target population is included, it should be in the early stages of PD defined as Hoehn and Yahr stages 1-3 in Off (untreated); (4) iRBD patients with soft neurologic dysfunction and with operational criteria established by the consensus of study investigators; (5) patients with mild cognitive impairment (MCI); and (6) optimally treated comorbid OSA. Twenty-four exclusion criteria were identified. The primary outcome measure for RBD treatment trials was determined to be the Clinical Global Impression (CGI) efficacy index, consisting of a four-point scale with a four-point side-effect scale. Assessment of video-polysomnographic (vPSG) changes holds promise but is costly and needs further elaboration. Secondary outcome measures include sleep diaries; sleepiness scales; PD sleep scale 2 (PDSS-2); serial motor examinations; cognitive indices; mood and anxiety indices; assessment of frequency of falls, gait impairment, and apathy; fatigue severity scale; and actigraphy and customized bed alarm systems. Consensus also was established for evaluating the clinical and vPSG aspects of RBD. End points for neuroprotective trials in RBD, taking lessons from research in PD, should be focused on the ultimate goal of determining the performance of disease-modifying agents. To date no compound with convincing evidence of disease-modifying or neuroprotective efficacy has been identified in PD. Nevertheless, iRBD patients are considered ideal candidates for neuroprotective studies. CONCLUSIONS: The IRBD-SG provides an important platform for developing multinational collaborative studies on RBD such as on environmental risk factors for iRBD, as recently reported in a peer-reviewed journal article, and on controlled active treatment studies for symptomatic and neuroprotective therapy that emerged during the 2011 consensus conference in Marburg, Germany, as described in our report.

25 Article Comparison of the clinical features of rapid eye movement sleep behavior disorder in patients with Parkinson's disease and multiple system atrophy. 2011

Nomura, Takashi / Inoue, Yuichi / Högl, Birgit / Uemura, Yusuke / Yasui, Kenichi / Sasai, Taeko / Namba, Kazuyoshi / Nakashima, Kenji. ·Division of Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University, Yonago, Japan. ntnomura@med.tottori-u.ac.jp ·Psychiatry Clin Neurosci · Pubmed #21507133.

ABSTRACT: AIMS: The aim of this study was to evaluate differences in the clinical presentation and polysomnographic characteristics of rapid eye movement sleep behavior disorder (RBD) between patients with Parkinson's disease (PD) and those with multiple system atrophy (MSA). METHODS: We conducted clinical interviews examining RBD symptoms, including violent and non-violent behaviors, in 49 patients with PD and 16 patients with MSA (as well as their bed partners) and performed polysomnography on all subject patients. RESULTS: Twenty-seven patients with PD (55.1%) and 11 patients with MSA (68.8%) had rapid eye movement sleep without atonia (RWA) on polysomnogram. The relative amounts of RWA were quite similar between the two groups. For most of the RWA-positive patients in both groups, RBD symptoms remained non-violent or silent. RBD symptoms in PD patients seemed to increase with the course of PD, while most of the RBD symptoms in the MSA patients occurred just prior to or at the onset of MSA and then disappeared within a short period. CONCLUSION: Although PD and MSA frequently accompany RWA, RBD symptoms often remain non-violent or silent. Differences in the course of RBD symptoms in patients with PD and MSA may reflect the difference in the degeneration process of the two disorders.

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