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Parkinson Disease: HELP
Articles by Daniel A. Berg
Based on 170 articles published since 2008
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Between 2008 and 2019, D. Berg wrote the following 170 articles about Parkinson Disease.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7
1 Editorial Biomarkers for PD: How can we approach complexity? 2013

Berg, Daniela / Bandmann, Oliver. · ·Neurology · Pubmed #23325899.

ABSTRACT: -- No abstract --

2 Review Cognitive changes in prodromal Parkinson's disease: A review. 2017

Fengler, Sophie / Liepelt-Scarfone, Inga / Brockmann, Kathrin / Schäffer, Eva / Berg, Daniela / Kalbe, Elke. ·Department of Medical Psychology ǀ Neuropsychology and Gender Studies & Center for Neuropsychological Diagnostics and Intervention (CeNDI), University Hospital Cologne, Cologne, Germany. · Psychological Gerontology, Institute of Gerontology, University of Vechta, Vechta, Germany. · Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. · German Center of Neurodegenerative Diseases (DZNE), University of Tübingen, Tübingen, Germany. · Department of Neurology, Christian-Albrechts-University, Kiel, Kiel, Germany. ·Mov Disord · Pubmed #28980730.

ABSTRACT: Although other nonmotor phenomena representing possible prodromal symptoms of Parkinson's disease have been described in some detail, the occurrence and characteristics of cognitive decline in this early phase of the disease are less well understood. The aim of this review is to summarize the current state of research on cognitive changes in prodromal PD. Only a small number of longitudinal studies have been conducted that examined cognitive function in individuals with a subsequent PD diagnosis. However, when we consider data from at-risk groups, the evidence suggests that cognitive decline may occur in a substantial number of individuals who have the potential for developing PD. In terms of specific cognitive domains, executive function in particular and, less frequently, memory scores are reduced. Prospective longitudinal studies are thus needed to clarify whether cognitive, and specifically executive, decline might be added to the prodromal nonmotor symptom complex that may precede motor manifestations of PD by years and may help to update the risk scores used for early identification of PD. © 2017 International Parkinson and Movement Disorder Society.

3 Review Past, present, and future of Parkinson's disease: A special essay on the 200th Anniversary of the Shaking Palsy. 2017

Obeso, J A / Stamelou, M / Goetz, C G / Poewe, W / Lang, A E / Weintraub, D / Burn, D / Halliday, G M / Bezard, E / Przedborski, S / Lehericy, S / Brooks, D J / Rothwell, J C / Hallett, M / DeLong, M R / Marras, C / Tanner, C M / Ross, G W / Langston, J W / Klein, C / Bonifati, V / Jankovic, J / Lozano, A M / Deuschl, G / Bergman, H / Tolosa, E / Rodriguez-Violante, M / Fahn, S / Postuma, R B / Berg, D / Marek, K / Standaert, D G / Surmeier, D J / Olanow, C W / Kordower, J H / Calabresi, P / Schapira, A H V / Stoessl, A J. ·HM CINAC, Hospital Universitario HM Puerta del Sur, Mostoles, Madrid, Spain. · Universidad CEU San Pablo, Madrid, Spain. · CIBERNED, Madrid, Spain. · Department of Neurology, Philipps University, Marburg, Germany. · Parkinson's Disease and Movement Disorders Department, HYGEIA Hospital and Attikon Hospital, University of Athens, Athens, Greece. · Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA. · Department of Neurology, Medical University Innsbruck, Innsbruck, Austria. · Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J Safra Program in Parkinson's Disease, Toronto Western Hospital, Toronto, Canada. · Department of Medicine, University of Toronto, Toronto, Canada. · Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Parkinson's Disease and Mental Illness Research, Education and Clinical Centers (PADRECC and MIRECC), Corporal Michael J. Crescenz Veteran's Affairs Medical Center, Philadelphia, Pennsylvania, USA. · Medical Sciences, Newcastle University, Newcastle, UK. · Brain and Mind Centre, Sydney Medical School, The University of Sydney, Sydney, Australia. · School of Medical Sciences, University of New South Wales and Neuroscience Research Australia, Sydney, Australia. · Université de Bordeaux, Institut des Maladies Neurodégénératives, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5293, Institut des Maladies Neurodégénératives, Bordeaux, France. · China Academy of Medical Sciences, Institute of Lab Animal Sciences, Beijing, China. · Departments of Neurology, Pathology, and Cell Biology, the Center for Motor Neuron Biology and Disease, Columbia University, New York, New York, USA. · Columbia Translational Neuroscience Initiative, Columbia University, New York, New York, USA. · Institut du Cerveau et de la Moelle épinière - ICM, Centre de NeuroImagerie de Recherche - CENIR, Sorbonne Universités, UPMC Univ Paris 06, Inserm U1127, CNRS UMR 7225, Paris, France. · Groupe Hospitalier Pitié-Salpêtrière, Paris, France. · Clinical Sciences Department, Newcastle University, Newcastle, UK. · Department of Nuclear Medicine, Aarhus University, Aarhus, Denmark. · Human Neurophysiology, Sobell Department, UCL Institute of Neurology, London, UK. · Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. · Department of Neurology, Emory University School of Medicine, Atlanta, Georgia, USA. · Morton and Gloria Shulman Movement Disorders Centre and the Edmond J Safra Program in Parkinson's disease, Toronto Western Hospital, University of Toronto, Toronto, Canada. · Movement Disorders and Neuromodulation Center, Department of Neurology, University of California-San Francisco, San Francisco, California, USA. · Parkinson's Disease Research, Education and Clinical Center, San Francisco Veterans Affairs Medical Center, San Francisco, California, USA. · Veterans Affairs Pacific Islands Health Care System, Honolulu, Hawaii, USA. · Parkinson's Institute, Sunnyvale, California, USA. · Institute of Neurogenetics, University of Luebeck, Luebeck, Germany. · Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands. · Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, Texas, USA. · Department of Neurosurgery, Toronto Western Hospital, University of Toronto, Toronto, Canada. · Department of Neurology, Universitätsklinikum Schleswig-Holstein, Christian Albrechts University Kiel, Kiel, Germany. · Department of Medical Neurobiology, Institute of Medical Research Israel-Canada, Jerusalem, Israel. · Edmond and Lily Safra Center for Brain Sciences, The Hebrew University, Jerusalem, Israel. · Department of Neurosurgery, Hadassah University Hospital, Jerusalem, Israel. · Parkinson's Disease and Movement Disorders Unit, Neurology Service, Institut Clínic de Neurociències, Hospital Clínic de Barcelona, Barcelona, Spain. · Department of Medicine, Universitat de Barcelona, IDIBAPS, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) Barcelona, Spain. · Movement Disorders Clinic, Clinical Neurodegenerative Research Unit, Mexico City, Mexico. · Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico. · Department of Neurology, Columbia University Medical Center, New York, New York, USA. · Department of Neurology, McGill University, Montreal General Hospital, Montreal, Quebec, Canada. · Klinik für Neurologie, UKSH, Campus Kiel, Christian-Albrechts-Universität, Kiel, Germany. · Institute for Neurodegenerative Disorders, New Haven, Connecticut, USA. · Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA. · Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA. · Departments of Neurology and Neuroscience, Mount Sinai School of Medicine, New York, New York, USA. · Research Center for Brain Repair, Rush University Medical Center, Chicago, Illinois, USA. · Neuroscience Graduate Program, Rush University Medical Center, Chicago, Illinois, USA. · Neurological Clinic, Department of Medicine, Hospital Santa Maria della Misericordia, University of Perugia, Perugia, Italy. · Laboratory of Neurophysiology, Santa Lucia Foundation, IRCCS, Rome, Italy. · University Department of Clinical Neurosciences, UCL Institute of Neurology, University College London, London, UK. · Pacific Parkinson's Research Centre, Division of Neurology & Djavadf Mowafaghian Centre for Brain Health, University of British Columbia, British Columbia, Canada. · Vancouver Coastal Health, Vancouver, British Columbia, Canada. ·Mov Disord · Pubmed #28887905.

ABSTRACT: This article reviews and summarizes 200 years of Parkinson's disease. It comprises a relevant history of Dr. James Parkinson's himself and what he described accurately and what he missed from today's perspective. Parkinson's disease today is understood as a multietiological condition with uncertain etiopathogenesis. Many advances have occurred regarding pathophysiology and symptomatic treatments, but critically important issues are still pending resolution. Among the latter, the need to modify disease progression is undoubtedly a priority. In sum, this multiple-author article, prepared to commemorate the bicentenary of the shaking palsy, provides a historical state-of-the-art account of what has been achieved, the current situation, and how to progress toward resolving Parkinson's disease. © 2017 International Parkinson and Movement Disorder Society.

4 Review Dopaminergic Therapies for Non-motor Symptoms in Parkinson's Disease. 2017

Schaeffer, Eva / Berg, Daniela. ·Department of Neurology, Christians-Albrechts University, Arnold-Heller-Str. 3, Haus 41, Kiel, 24105, Germany. eva.schaeffer@uksh.de. · Department of Neurology, Christians-Albrechts University, Arnold-Heller-Str. 3, Haus 41, Kiel, 24105, Germany. · Department of Neurodegeneration, Hertie-Institute of Clinical Brain Research, Tuebingen, Germany. ·CNS Drugs · Pubmed #28643183.

ABSTRACT: Apart from the typical motor symptoms, Parkinson's disease is characterized by a wide range of different non-motor symptoms, which are highly prevalent in all stages of the disease and have an incisive influence on quality of life. Moreover, their treatment continues to be challenging. In this review, we critically summarize the evidence for the impact of dopaminergic therapies on non-motor symptoms in Parkinson's disease. We performed a PubMed search to identify relevant clinical studies that investigated the response of non-motor symptoms to dopaminergic therapy. In the domain of neuropsychiatric disturbances, there is increasing evidence that dopamine agonists can ameliorate depression or anxiety. Other neuropsychiatric symptoms such as psychosis or impulse control disorders can also be worsened or even be induced by dopaminergic agents. For the treatment of sleep disturbances, it is essential to identify different subtypes of sleep pathologies. While there is for example profound evidence for the effectiveness of dopaminergic medication for the treatment of restless legs syndrome and sleep fragmentation, evidence for an improvement of rapid eye movement sleep behavior disorder is lacking. With regard to the broad spectrum of autonomic disturbances, response to dopaminergic treatment seems to differ largely, with on the one hand, some evidence for an improvement of sexual function or sweating with dopaminergic treatment, while on the other hand, constipation can be worsened. Finally, the analysis of sensory deficits reveals that some forms of pain, in particular fluctuation-dependent dystonic pain, can be well addressed by adapting the dopaminergic therapy, while no effect has been seen so far for hyposmia or visual deficits. Moreover, the occurrence of non-motor fluctuations is gaining increased attention, as they can be specifically addressed by a more continuous dopaminergic intake. Taken together, there is evidence of a good response of some (but not all) non-motor symptoms to dopaminergic therapy, which must be individually adapted to the special spectrum of symptoms.

5 Review Global, Yet Incomplete Overview of Cohort Studies in Parkinson's disease. 2017

Heinzel, Sebastian / Lerche, Stefanie / Maetzler, Walter / Berg, Daniela. ·Department of Neurology, Christian-Albrechts-University, Kiel, Germany. · German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany. · Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany. ·J Parkinsons Dis · Pubmed #28582871.

ABSTRACT: BACKGROUND: Parkinson's disease (PD) is characterized by heterogeneity and multifactorial longitudinal changes. To identify PD subtypes and factors influencing the disease course, multiple cohort studies have been designed globally. Knowledge about existing cohorts is pivotal to foster collaboration, which may help to advance the understanding of PD. OBJECTIVE: To raise the awareness about PD cohorts and potential global collaboration opportunities. METHODS: Observational cohort studies in clinical PD were identified by a European working group (JPND BioLoC-PD) and through literature search. Using a structured survey investigators of 44 cohorts provided basic information on cohorts and assessments performed. RESULTS: For the 44 cohorts (32% on early/de-novo PD), 14.666 participants (cohorts' median: 138; range: 23-3.090), a median 1.5-year follow-up interval (0.5-4 years) and a median (planned) observational period of 5 years (1-20 years) were indicated. All studies have assessed motor functions often using rating scales (UPDRS-III; 93% of studies) and less frequently quantitative gait/balance (25%) or fine motor assessments (27%). Cognitive (100%), neuropsychiatric (91%), daily living (78%), sleep (70%), sensory (63%), and gastrointestinal/autonomic (55%) assessments were common and often comparable. Neuroimaging data (82%) and biomaterial (69%) have been collected in many studies. Surprisingly, possible disease modifiers, such as sport/physical activity (11%), have rarely been assessed. CONCLUSIONS: Existing data of PD cohorts provide vast collaboration opportunities. We propose to establish a comprehensive, up-to-date, open-access internet platform with easy-to-use search tools of PD cohort descriptions and potentially available data. Bringing researchers together to enable collaborative joint, meta- and replication analyses is timely and necessary to advance PD research ultimately required for an understanding of PD that can be translated into more effective therapies.

6 Review The New Diagnostic Criteria for Parkinson's Disease. 2017

Postuma, Ronald B / Berg, Daniela. ·L7-305 Montreal General Hospital, Montreal, Canada. Electronic address: ron.postuma@mcgill.ca. · Christian-Albrechts-University of Kiel, Kiel, Germany. ·Int Rev Neurobiol · Pubmed #28554421.

ABSTRACT: This chapter summarizes the advances in diagnosis of Parkinson's disease (PD) that were encapsulated in new International Parkinson Disease and Movement Disorders Society diagnostic criteria for PD. Numerous changes in our understanding of PD have occurred, including our understanding of the nonmotor profile of disease, the recognition of PD as a synucleinopathy, identification of genetic causes, novel hypotheses about spread of disease, etc. These have been reflected in a new definition of PD, which includes a clinicogenetic subtype of PD, removes dementia with Lewy Bodies as an exclusion criterion against PD, and recognizes multiple stages of early disease. The Clinical Diagnostic Criteria for PD reflect these changes and offer a new standardized diagnostic method for use in clinical research and even clinical practice. The criteria for prodromal PD use a method not seen in previous diagnostic criteria; they rely upon published studies of PD predictors to calculate the probability that any individual will develop PD. The field of PD is constantly advancing, and our methods of diagnosis need to advance with it; one hopes for a future filled with constant revisions and updates in our diagnostic methodology.

7 Review [New therapy approaches for Parkinson's disease]. 2017

Brockmann, K / Berg, D. ·Zentrum für Neurologie, Abteilung Neurodegeneration, Hertie-Institut für klinische Hirnforschung, Deutsches Zentrum für Neurodegenerative Erkrankungen, Universität Tübingen, Hoppe-Seyler-Straße 3, 72076, Tübingen, Deutschland. kathrin.brockmann@uni-tuebingen.de. · Zentrum für Neurologie, Abteilung Neurodegeneration, Hertie-Institut für klinische Hirnforschung, Deutsches Zentrum für Neurodegenerative Erkrankungen, Universität Tübingen, Hoppe-Seyler-Straße 3, 72076, Tübingen, Deutschland. · Klinik für Neurologie, Christian-Albrechts-Universität, Kiel, Deutschland. ·Nervenarzt · Pubmed #28289790.

ABSTRACT: Over the last years major advances have been made in the identification of specific pathways underlying the pathophysiology of subgroups of patients with Parkinson' disease. These pathways include mitochondrial and lysosomal dysfunction as well as inflammatory patterns and represent the basis for new causative and disease-modifying treatment strategies, possibly not only for the respective subgroups of patients but hopefully also for the majority of patients with idiopathic Parkinson's disease. This article highlights the main treatment strategies focusing on causative and disease course-modifying strategies as well as quality of life.

8 Review Advances in markers of prodromal Parkinson disease. 2016

Postuma, Ronald B / Berg, Daniela. ·Department of Neurology, L7-305 Montreal General Hospital, 1650 Cedar Avenue, Montreal H3G1A4, Canada. · Department of Neurology, Christian-Albrechts-University of Kiel, Arnold-Heller-Straße 3, 24105 Kiel, Germany. · Department of neurodegeneration, Hertie Institute of Clinical Brain Research, Hoppe, Seyler-Straße 3, 72076 Tübingen, Germany. ·Nat Rev Neurol · Pubmed #27786242.

ABSTRACT: Efforts to develop neuroprotective therapy for Parkinson disease (PD) are focusing on the early stages of disease, which offer the best opportunity to intervene. Early PD can be divided into preclinical, prodromal and clinical stages; in this Review, we focus on the prodromal stage and markers that can be used to identify prodromal PD. We consider the necessary properties of a marker, before providing an overview of the proven and potential markers of prodromal PD, including clinical nonmotor markers, clinical motor markers, neuroimaging markers and tissue biomarkers. Markers for which the ability to predict conversion to PD is supported by the strongest evidence include olfactory loss, REM sleep behaviour disorder and constipation. Markers with the highest diagnostic strength include REM sleep behaviour disorder, dopaminergic imaging and subtle motor parkinsonism. The lead time - the period between the appearance of a marker and conversion to PD - is highly variable between markers, ranging from 5 years for impaired motor performance to >20 years for autonomic symptoms. The cost of screening for these markers also varies dramatically: some require just questionnaires, whereas others require sophisticated scanning techniques. Finally, we summarize how prodromal and risk markers can be combined to estimate the probability that an individual has prodromal PD, with a focus on the International Parkinson Disease and Movement Disorders Society (MDS) Prodromal Parkinson Criteria.

9 Review Health-Related Quality of Life in patients with Parkinson's disease--A systematic review based on the ICF model. 2016

van Uem, Janet M T / Marinus, Johan / Canning, Colleen / van Lummel, Rob / Dodel, Richard / Liepelt-Scarfone, Inga / Berg, Daniela / Morris, Meg E / Maetzler, Walter. ·Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, Center of Neurology, University of Tuebingen, Tuebingen, Germany; German Center for Neurodegenerative Diseases, DZNE, Tuebingen, Germany. Electronic address: janet.uem@uni-tuebingen.de. · Department of Neurology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. Electronic address: J.Marinus@lumc.nl. · Clinical and Rehabilitation Sciences Research Group, Faculty of Health Sciences, The University of Sydney, PO Box 170, Lidcombe, Sydney 1825, NSW, Australia. Electronic address: Colleen.canning@sydney.edu.au. · McRoberts, Raamweg 43, 2596 HN The Hague, The Netherlands. Electronic address: R.vanLummel@mcroberts.nl. · Department of Neurology, Philipps-University, Baldingerstrasse, D-35043 Marburg, Germany. Electronic address: Dodel@med.uni-marburg.de. · Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, Center of Neurology, University of Tuebingen, Tuebingen, Germany; German Center for Neurodegenerative Diseases, DZNE, Tuebingen, Germany. Electronic address: inga.liepelt@uni-tuebingen.de. · Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, Center of Neurology, University of Tuebingen, Tuebingen, Germany; German Center for Neurodegenerative Diseases, DZNE, Tuebingen, Germany. Electronic address: daniela.berg@uni-tuebingen.de. · Physiotherapy, School of Allied Health, College of Science, Health and Engineering, La Trobe, Melbourne 3086, VIC, Australia. Electronic address: M.morris@latrobe.edu.au. · Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, Center of Neurology, University of Tuebingen, Tuebingen, Germany; German Center for Neurodegenerative Diseases, DZNE, Tuebingen, Germany. Electronic address: walter.maetzler@uni-tuebingen.de. ·Neurosci Biobehav Rev · Pubmed #26645499.

ABSTRACT: We analyzed features associated with a reduction in Health-Related Quality of Life (HRQoL) in people with idiopathic Parkinson's disease (PD). As a new approach, features were embedded in the WHO framework for measuring health and disability, the ICF model. From 609 articles screened, 114 articles were included. Features aligned with the ICF's body functions and structures domain (BFS) were investigated more often than personal features, activities of daily living, environmental factors, and participation in societal roles (95, 42, 35, 29 and 14 times, respectively). The strongest associations were found for the relationships between HRQoL and "psychosocial functioning" from the participation domain and HRQoL, and "mobility limitations" from the activities domain. For the BFS, non-motor symptoms were more closely associated with reduced HRQoL than motor symptoms. In conclusion, this systematic review (i) provides entirely new insights in the association of HRQoL with PD features, (ii) shows an imbalance between most extensively investigated and most relevant features for HRQoL, and (iii) demonstrates the usefulness of the ICF model for such an approach.

10 Review MDS research criteria for prodromal Parkinson's disease. 2015

Berg, Daniela / Postuma, Ronald B / Adler, Charles H / Bloem, Bastiaan R / Chan, Piu / Dubois, Bruno / Gasser, Thomas / Goetz, Christopher G / Halliday, Glenda / Joseph, Lawrence / Lang, Anthony E / Liepelt-Scarfone, Inga / Litvan, Irene / Marek, Kenneth / Obeso, José / Oertel, Wolfgang / Olanow, C Warren / Poewe, Werner / Stern, Matthew / Deuschl, Günther. ·Department of Neurodegeneration, Hertie-Institute for Clinical Brain Research and German Center for Neurodegenerative Diseases, Tuebingen, Germany. · Department of Neurology, Montreal General Hospital, Montreal, Quebec, Canada. · The Parkinson's Disease and Movement Disorders Center, Department of Neurology, Mayo Clinic, Scottsdale, Arizona, USA. · Department of Neurology, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Nijmegen, The Netherlands. · Xuanwu Hospital of Capitol of Medical University, Beijing, China. · Hopital De La Salpetriere, Paris, France. · Rush University Medical Center, Chicago, Illinois, USA. · Neuroscience Research Australia & University of NSW, Randwick, Australia. · Department of Epidemiology and Biostatistics, McGill University, Montreal, Quebec, Canada. · Division of Neurology, Toronto Western Hospital, Toronto, Ontario, Canada. · Department of Neurosciences, University of California San Diego, La Jolla, California, USA. · Institute for Neurodegenerative Disorders, New Haven, Connecticut, USA. · University of Navarra-FIMA, Pamplona, Spain. · Department of Neurology, Philipps University of Marburg, Marburg, Germany. · Department of Neurology, The Mount Sinai Hospital, New York, New York, USA. · Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. · Penn Neurological Institute, Philadelphia, Pennsylvania, USA. · Department of Neurology, Christian-Albrechts University, Kiel, Germany. ·Mov Disord · Pubmed #26474317.

ABSTRACT: This article describes research criteria and probability methodology for the diagnosis of prodromal PD. Prodromal disease refers to the stage wherein early symptoms or signs of PD neurodegeneration are present, but classic clinical diagnosis based on fully evolved motor parkinsonism is not yet possible. Given the lack of clear neuroprotective/disease-modifying therapy for prodromal PD, these criteria were developed for research purposes only. The criteria are based upon the likelihood of prodromal disease being present with probable prodromal PD defined as ≥80% certainty. Certainty estimates rely upon calculation of an individual's risk of having prodromal PD, using a Bayesian naïve classifier. In this methodology, a previous probability of prodromal disease is delineated based upon age. Then, the probability of prodromal PD is calculated by adding diagnostic information, expressed as likelihood ratios. This diagnostic information combines estimates of background risk (from environmental risk factors and genetic findings) and results of diagnostic marker testing. In order to be included, diagnostic markers had to have prospective evidence documenting ability to predict clinical PD. They include motor and nonmotor clinical symptoms, clinical signs, and ancillary diagnostic tests. These criteria represent a first step in the formal delineation of early stages of PD and will require constant updating as more information becomes available.

11 Review MDS clinical diagnostic criteria for Parkinson's disease. 2015

Postuma, Ronald B / Berg, Daniela / Stern, Matthew / Poewe, Werner / Olanow, C Warren / Oertel, Wolfgang / Obeso, José / Marek, Kenneth / Litvan, Irene / Lang, Anthony E / Halliday, Glenda / Goetz, Christopher G / Gasser, Thomas / Dubois, Bruno / Chan, Piu / Bloem, Bastiaan R / Adler, Charles H / Deuschl, Günther. ·Department of Neurology, Montreal General Hospital, Montreal, Quebec, Canada. · Department of Neurodegeneration, Hertie-Institute for Clinical Brain Research and German Center for Neurodegenerative Diseases, Tuebingen, Germany. · Penn Neurological Institute, Philadelphia, Pennsylvania, USA. · Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. · Department of Neurology, The Mount Sinai Hospital, New York, New York, USA. · Department of Neurology, Philipps University of Marburg, Marburg, Germany. · University of Navarra-FIMA, Pamplona, Spain. · Institute for Neurodegenerative Disorders, New Haven, Connecticut, USA. · Department of Neurosciences, UC San Diego, La Jolla, California, USA. · Division of Neurology, Toronto Western Hospital, Toronto, Ontario, Canada. · Neuroscience Research Australia & University of NSW, Randwick, Australia. · Rush University Medical Center, Chicago, Illinois, USA. · Hopital De La Salpetriere, Paris, France. · Xuanwu Hospital of Capitol of Medical University, Beijing, Peoples Republic of China. · Department of Neurology, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Netherlands. · The Parkinson's Disease and Movement Disorders Center, Department of Neurology, Mayo Clinic, Scottsdale, Arizona, USA. · Department of Neurology, Christian-Albrechts University, Kiel, Germany. ·Mov Disord · Pubmed #26474316.

ABSTRACT: This document presents the Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's disease (PD). The Movement Disorder Society PD Criteria are intended for use in clinical research but also may be used to guide clinical diagnosis. The benchmark for these criteria is expert clinical diagnosis; the criteria aim to systematize the diagnostic process, to make it reproducible across centers and applicable by clinicians with less expertise in PD diagnosis. Although motor abnormalities remain central, increasing recognition has been given to nonmotor manifestations; these are incorporated into both the current criteria and particularly into separate criteria for prodromal PD. Similar to previous criteria, the Movement Disorder Society PD Criteria retain motor parkinsonism as the core feature of the disease, defined as bradykinesia plus rest tremor or rigidity. Explicit instructions for defining these cardinal features are included. After documentation of parkinsonism, determination of PD as the cause of parkinsonism relies on three categories of diagnostic features: absolute exclusion criteria (which rule out PD), red flags (which must be counterbalanced by additional supportive criteria to allow diagnosis of PD), and supportive criteria (positive features that increase confidence of the PD diagnosis). Two levels of certainty are delineated: clinically established PD (maximizing specificity at the expense of reduced sensitivity) and probable PD (which balances sensitivity and specificity). The Movement Disorder Society criteria retain elements proven valuable in previous criteria and omit aspects that are no longer justified, thereby encapsulating diagnosis according to current knowledge. As understanding of PD expands, the Movement Disorder Society criteria will need continuous revision to accommodate these advances.

12 Review Developments in the role of transcranial sonography for the differential diagnosis of parkinsonism. 2015

Pilotto, Andrea / Yilmaz, Rezzak / Berg, Daniela. ·Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. ·Curr Neurol Neurosci Rep · Pubmed #26008814.

ABSTRACT: In the last two decades transcranial sonography (TCS) has developed as a valuable, supplementary tool in the diagnosis and differential diagnosis of movement disorders. In this review, we highlight recent evidence supporting TCS as a reliable method in the differential diagnosis of parkinsonism, combining substantia nigra (SN), basal ganglia and ventricular system findings. Moreover, several studies support SN hyperechogenicity as one of most important risk factors for Parkinson's disease (PD). The advantages of TCS include short investigation time, low cost and lack of radiation. Principal limitations are still the dependency on the bone window and operator experience. New automated algorithms may reduce the role of investigator skill in the assessment and interpretation, increasing TCS diagnostic reliability. Based on the convincing evidence available, the EFNS accredited the method of TCS a level A recommendation for supporting the diagnosis of PD and its differential diagnosis from secondary and atypical parkinsonism. An increasing number of training programmes is extending the use of this technique in clinical practice.

13 Review Pharmacological strategies for the management of levodopa-induced dyskinesia in patients with Parkinson's disease. 2014

Schaeffer, Eva / Pilotto, Andrea / Berg, Daniela. ·Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, University of Tuebingen, Hoppe Seyler-Strasse 3, 72076, Tübingen, Germany. ·CNS Drugs · Pubmed #25342080.

ABSTRACT: L-Dopa-induced dyskinesias (LID) are the most common adverse effects of long-term dopaminergic therapy in Parkinson's disease (PD). However, the exact mechanisms underlying dyskinesia are still unclear. For a long time, nigrostriatal degeneration and pulsatile stimulation of striatal postsynaptic receptors have been highlighted as the key factors for the development of LID. In recent years, PD models have revealed a wide range of non-dopaminergic neurotransmitter systems involved in pre- and postsynaptic changes and thereby contributing to the pathophysiology of LID. In the current review, we focus on therapeutic LID targets, mainly based on agents acting on dopaminergic, glutamatergic, serotoninergic, adrenergic, and cholinergic systems. Despite a large number of clinical trials, currently only amantadine and, to a lesser extent, clozapine are being used as effective strategies in the treatment of LID in clinical settings. Thus, in the second part of the article, we review the placebo-controlled trials on LID treatment in order to disentangle the changing scenario of drug development. Promising results include the extension of L-dopa action without inducing LID of the novel monoamine oxidase B- and glutamate-release inhibitor safinamide; however, this had no obvious effect on existing LID. Others, like the metabotropic glutamate-receptor antagonist AFQ056, showed promising results in some of the studies; however, confirmation is still lacking. Thus, to date, strategies of continuous dopaminergic stimulation seem the most promising to prevent or ameliorate LID. The success of future therapeutic strategies once moderate to severe LID occur will depend on the translation from preclinical experimental models into clinical practice in a bidirectional process.

14 Review The significance of GBA for Parkinson's disease. 2014

Brockmann, Kathrin / Berg, Daniela. ·Department of Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany, Kathrin.Brockmann@uni-tuebingen.de. ·J Inherit Metab Dis · Pubmed #24894157.

ABSTRACT: From the first descriptions of Parkinson's disease (PD) and Gaucher's disease (GD) in the nineteenth century, it took more than 100 years to discover the link between the GBA gene and Parkinsonism. The observation that mutations in the GBA gene represent the most common genetic risk factor for PD so far only came into focus because of astute clinical observation of Gaucher patients and their families. In this review, we (i) outline how GBA was identified as a genetic risk factor for Parkinsonism, (ii) present clinical characteristics of GBA-associated Parkinsonism, (iii) discuss possible mechanisms of the underlying pathogenesis in GBA-associated Parkinsonism, and (iv) provide an outlook on potentially new areas of research and treatment that arise from this important discovery.

15 Review Time to redefine PD? Introductory statement of the MDS Task Force on the definition of Parkinson's disease. 2014

Berg, Daniela / Postuma, Ronald B / Bloem, Bastiaan / Chan, Piu / Dubois, Bruno / Gasser, Thomas / Goetz, Christopher G / Halliday, Glenda M / Hardy, John / Lang, Anthony E / Litvan, Irene / Marek, Kenneth / Obeso, José / Oertel, Wolfgang / Olanow, C Warren / Poewe, Werner / Stern, Matthew / Deuschl, Günther. ·Department of Neurodegeneration, Hertie Institute for Clinical Brain Research and German Center of Neurodegenerative Diseases, Tuebingen, Germany. ·Mov Disord · Pubmed #24619848.

ABSTRACT: With advances in knowledge disease, boundaries may change. Occasionally, these changes are of such a magnitude that they require redefinition of the disease. In recognition of the profound changes in our understanding of Parkinson's disease (PD), the International Parkinson and Movement Disorders Society (MDS) commissioned a task force to consider a redefinition of PD. This review is a discussion article, intended as the introductory statement of the task force. Several critical issues were identified that challenge current PD definitions. First, new findings challenge the central role of the classical pathologic criteria as the arbiter of diagnosis, notably genetic cases without synuclein deposition, the high prevalence of incidental Lewy body (LB) deposition, and the nonmotor prodrome of PD. It remains unclear, however, whether these challenges merit a change in the pathologic gold standard, especially considering the limitations of alternate gold standards. Second, the increasing recognition of dementia in PD challenges the distinction between diffuse LB disease and PD. Consideration might be given to removing dementia as an exclusion criterion for PD diagnosis. Third, there is increasing recognition of disease heterogeneity, suggesting that PD subtypes should be formally identified; however, current subtype classifications may not be sufficiently robust to warrant formal delineation. Fourth, the recognition of a nonmotor prodrome of PD requires that new diagnostic criteria for early-stage and prodromal PD should be created; here, essential features of these criteria are proposed. Finally, there is a need to create new MDS diagnostic criteria that take these changes in disease definition into consideration.

16 Review EFNS/MDS-ES/ENS [corrected] recommendations for the diagnosis of Parkinson's disease. 2013

Berardelli, A / Wenning, G K / Antonini, A / Berg, D / Bloem, B R / Bonifati, V / Brooks, D / Burn, D J / Colosimo, C / Fanciulli, A / Ferreira, J / Gasser, T / Grandas, F / Kanovsky, P / Kostic, V / Kulisevsky, J / Oertel, W / Poewe, W / Reese, J-P / Relja, M / Ruzicka, E / Schrag, A / Seppi, K / Taba, P / Vidailhet, M. ·Dipartimento di Neurologia e Psichiatria and IRCCS NEUROMED Institute, Sapienza, Università di Roma, Rome, Italy. alfredo.berardelli@uniroma1.it ·Eur J Neurol · Pubmed #23279440.

ABSTRACT: BACKGROUND: A Task Force was convened by the EFNS/MDS-ES Scientist Panel on Parkinson's disease (PD) and other movement disorders to systemically review relevant publications on the diagnosis of PD. METHODS: Following the EFNS instruction for the preparation of neurological diagnostic guidelines, recommendation levels have been generated for diagnostic criteria and investigations. RESULTS: For the clinical diagnosis, we recommend the use of the Queen Square Brain Bank criteria (Level B). Genetic testing for specific mutations is recommended on an individual basis (Level B), taking into account specific features (i.e. family history and age of onset). We recommend olfactory testing to differentiate PD from other parkinsonian disorders including recessive forms (Level A). Screening for pre-motor PD with olfactory testing requires additional tests due to limited specificity. Drug challenge tests are not recommended for the diagnosis in de novo parkinsonian patients. There is an insufficient evidence to support their role in the differential diagnosis between PD and other parkinsonian syndromes. We recommend an assessment of cognition and a screening for REM sleep behaviour disorder, psychotic manifestations and severe depression in the initial evaluation of suspected PD cases (Level A). Transcranial sonography is recommended for the differentiation of PD from atypical and secondary parkinsonian disorders (Level A), for the early diagnosis of PD and in the detection of subjects at risk for PD (Level A), although the technique is so far not universally used and requires some expertise. Because specificity of TCS for the development of PD is limited, TCS should be used in conjunction with other screening tests. Conventional magnetic resonance imaging and diffusion-weighted imaging at 1.5 T are recommended as neuroimaging tools that can support a diagnosis of multiple system atrophy (MSA) or progressive supranuclear palsy versus PD on the basis of regional atrophy and signal change as well as diffusivity patterns (Level A). DaTscan SPECT is registered in Europe and the United States for the differential diagnosis between degenerative parkinsonisms and essential tremor (Level A). More specifically, DaTscan is indicated in the presence of significant diagnostic uncertainty such as parkinsonism associated with neuroleptic exposure and atypical tremor manifestations such as isolated unilateral postural tremor. Studies of [(123) I]MIBG/SPECT cardiac uptake may be used to identify patients with PD versus controls and MSA patients (Level A). All other SPECT imaging studies do not fulfil registration standards and cannot be recommended for routine clinical use. At the moment, no conclusion can be drawn as to diagnostic efficacy of autonomic function tests, neurophysiological tests and positron emission tomography imaging in PD. CONCLUSIONS: The diagnosis of PD is still largely based on the correct identification of its clinical features. Selected investigations (genetic, olfactory, and neuroimaging studies) have an ancillary role in confirming the diagnosis, and some of them could be possibly used in the near future to identify subjects in a pre-symptomatic phase of the disease.

17 Review Genetics and iron in the systems biology of Parkinson's disease and some related disorders. 2013

Funke, Claudia / Schneider, Susanne A / Berg, Daniela / Kell, Douglas B. ·Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, University of Tübingen, Otfried-Müller-Strasse 27, 72076 Tübingen, Germany. ·Neurochem Int · Pubmed #23220386.

ABSTRACT: The systems biology approach to complex diseases recognises that a potentially large number of biochemical network elements may be involved in disease progression, especially where positive feedback loops can be identified. Most of these network elements will be encoded by genes, for which different alleles may affect the network(s) differentially. A primary requirement is therefore to determine the relevant gene-network relationships. A corollary of this is that identification of the network should thereby allow one to 'explain' or account for any genetic associations. We apply this approach to Parkinson's disease, a disease characterised by apoptotic death of neurons of the substantia nigra, and coupled significantly to a derangement of iron metabolism. We thereby account for the involvement of various genes and biochemical pathways associated with Parkinsonism, including seemingly unconnected ones involving iron, α-synuclein, parkin, mitochondrial respiration and biology, ceramide production, lysosome biology, Lewy body formation, and so on. Although such an analysis necessarily recognises that there is no unitary 'cause' of Parkinson's, it also recognises that each of the elements contributing can or does effectively converge on a particular mode of apoptotic cell death in dopaminergic neurons, often involving iron-mediated hydroxyl radical formation. Overall, the systems biology approach allows us to propose at least one coherent synthesis of the rather disparate literature surrounding the aetiology of Parkinson's disease, and thereby to suggest some (synergistic) targets for ameliorating the disease and its progression.

18 Review Does structural neuroimaging reveal a disturbance of iron metabolism in Parkinson's disease? Implications from MRI and TCS studies. 2012

Gröger, Adriane / Berg, Daniela. ·Department of Neurodegeneration, Hertie Institute of Clinical Brain Research, and German Center of Neurodegenerative Diseases (DZNE), University of Tübingen, Hoppe-Seyler-Strasse 3, 72076, Tübingen, Germany. adriane.groeger@med.uni-tuebingen.de ·J Neural Transm (Vienna) · Pubmed #22875636.

ABSTRACT: A central role of iron in the pathogenesis of Parkinson's disease (PD) has been discussed for many years. Numerous studies using magnetic resonance imaging and transcranial sonography have been performed to detect alterations in tissue iron content of the substantia nigra. This manuscript reviews the findings of this still controversial issue and indicates that specific abnormalities that are suggested to be related to a disturbance of iron homeostasis may play an early role in the pathogenesis of PD.

19 Review Defining at-risk populations for Parkinson's disease: lessons from ongoing studies. 2012

Berg, Daniela / Marek, Ken / Ross, George W / Poewe, Werner. ·Department of Neurodegeneration, Hertie Institute of Clinical Brain Research and German Center of Neurodegenerative Diseases, University of Tübingen, Tübingen, Germany. daniela.berg@uni-tuebingen.de ·Mov Disord · Pubmed #22508284.

ABSTRACT: It is currently widely acknowledged that the natural history of PD includes a preclinical phase, and there are increasing efforts to identify markers that would allow the identification of individuals at risk for PD. Here, we discuss the issues related to defining at-risk populations for PD and review findings of current population-based cohorts that have reported potential biomarkers for PD, such as the Honolulu-Asia Aging Study (HAAS) and the PRIPS (Prospective Validation of Risk factors for the development of Parkinson Syndromes) study. We also discuss enriched risk cohorts designed to evaluate specificity and predictive value of markers exemplified by the PARS (Parkinson Associated Risk Study) and the TREND (Tübinger evaluation of Risk factors for the Early detection of NeuroDegeneration) study. Although there is still a long way to go, studies designed according to these concepts might eventually provide sufficient data to form the basis for future screening programs for PD risk to be applied at a population level.

20 Review Is pre-motor diagnosis possible? The European experience. 2012

Berg, Daniela. ·Department of Neurodegeneration, Hertie-Institute of Clinical Brain Research and German Center for Neurodegenerative Diseases, University of Tübingen, Tübingen, Germany. daniela.berg@uni-tuebingen.de ·Parkinsonism Relat Disord · Pubmed #22166433.

ABSTRACT: The increasing knowledge about an ongoing neurodegenerative process long before the diagnosis of Parkinson's disease (PD) can be made according to the current diagnostic criteria urges the need for an earlier diagnosis with the final aim of neuromodulatory and neuroprotective therapies. A number of risk, pre-motor and early motor markers are being discussed as potential markers to identify individuals who will develop the full picture of clinical PD. In Europe, studies like the PRIPS study (Prospective validation of Risk factors for the development of Parkinson Syndromes) are performed to determine the sensitivity and predictive value of markers. In enriched risk cohorts like cohorts of individuals with RBD (Rem sleep Behaviour Disorder) or the TREND study (Tübinger evaluation of Risk factors for Early detection of NeuroDegeneration) specificity of markers is determined and further markers are evaluated. Moreover, progression of markers in the pre-motor period is being evaluated in these studies; for example, in the PMPP study (Progression Markers in the suspected Pre-motor Phase) assessments are performed at shorter time intervals. Establishing sensitivity, specificity, predictive value and progression of markers in yet healthy individuals are hoped to lay the basis for future interventional trials before the onset of motor-PD.

21 Review Biomarker candidates of neurodegeneration in Parkinson's disease for the evaluation of disease-modifying therapeutics. 2012

Gerlach, Manfred / Maetzler, Walter / Broich, Karl / Hampel, Harald / Rems, Lucas / Reum, Torsten / Riederer, Peter / Stöffler, Albrecht / Streffer, Johannes / Berg, Daniela. ·Department for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Füchsleinstrasse 15, 97080 Würzburg, Germany. manfred.gerlach@uni-wuerzburg.de ·J Neural Transm (Vienna) · Pubmed #21755462.

ABSTRACT: Reliable biomarkers that can be used for early diagnosis and tracking disease progression are the cornerstone of the development of disease-modifying treatments for Parkinson's disease (PD). The German Society of Experimental and Clinical Neurotherapeutics (GESENT) has convened a Working Group to review the current status of proposed biomarkers of neurodegeneration according to the following criteria and to develop a consensus statement on biomarker candidates for evaluation of disease-modifying therapeutics in PD. The criteria proposed are that the biomarker should be linked to fundamental features of PD neuropathology and mechanisms underlying neurodegeneration in PD, should be correlated to disease progression assessed by clinical rating scales, should monitor the actual disease status, should be pre-clinically validated, and confirmed by at least two independent studies conducted by qualified investigators with the results published in peer-reviewed journals. To date, available data have not yet revealed one reliable biomarker to detect early neurodegeneration in PD and to detect and monitor effects of drug candidates on the disease process, but some promising biomarker candidates, such as antibodies against neuromelanin, pathological forms of α-synuclein, DJ-1, and patterns of gene expression, metabolomic and protein profiling exist. Almost all of the biomarker candidates were not investigated in relation to effects of treatment, validated in experimental models of PD and confirmed in independent studies.

22 Review Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis. 2011

van Es, Michael A / Schelhaas, Helenius J / van Vught, Paul W J / Ticozzi, Nicola / Andersen, Peter M / Groen, Ewout J N / Schulte, Claudia / Blauw, Hylke M / Koppers, Max / Diekstra, Frank P / Fumoto, Katsumi / LeClerc, Ashley Lyn / Keagle, Pamela / Bloem, Bastiaan R / Scheffer, Hans / van Nuenen, Bart F L / van Blitterswijk, Marka / van Rheenen, Wouter / Wills, Anne-Marie / Lowe, Patrick P / Hu, Guo-fu / Yu, Wenhao / Kishikawa, Hiroko / Wu, David / Folkerth, Rebecca D / Mariani, Claudio / Goldwurm, Stefano / Pezzoli, Gianni / Van Damme, Philip / Lemmens, Robin / Dahlberg, Caroline / Birve, Anna / Fernández-Santiago, Rubén / Waibel, Stefan / Klein, Christine / Weber, Markus / van der Kooi, Anneke J / de Visser, Marianne / Verbaan, Dagmar / van Hilten, Jacobus J / Heutink, Peter / Hennekam, Eric A M / Cuppen, Edwin / Berg, Daniela / Brown, Robert H / Silani, Vincenzo / Gasser, Thomas / Ludolph, Albert C / Robberecht, Wim / Ophoff, Roel A / Veldink, Jan H / Pasterkamp, R Jeroen / de Bakker, Paul I W / Landers, John E / van de Warrenburg, Bart P / van den Berg, Leonard H. ·Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, The Netherlands. ·Ann Neurol · Pubmed #22190368.

ABSTRACT: OBJECTIVE: Several studies have suggested an increased frequency of variants in the gene encoding angiogenin (ANG) in patients with amyotrophic lateral sclerosis (ALS). Interestingly, a few ALS patients carrying ANG variants also showed signs of Parkinson disease (PD). Furthermore, relatives of ALS patients have an increased risk to develop PD, and the prevalence of concomitant motor neuron disease in PD is higher than expected based on chance occurrence. We therefore investigated whether ANG variants could predispose to both ALS and PD. METHODS: We reviewed all previous studies on ANG in ALS and performed sequence experiments on additional samples, which allowed us to analyze data from 6,471 ALS patients and 7,668 controls from 15 centers (13 from Europe and 2 from the USA). We sequenced DNA samples from 3,146 PD patients from 6 centers (5 from Europe and 1 from the USA). Statistical analysis was performed using the variable threshold test, and the Mantel-Haenszel procedure was used to estimate odds ratios. RESULTS: Analysis of sequence data from 17,258 individuals demonstrated a significantly higher frequency of ANG variants in both ALS and PD patients compared to control subjects (p = 9.3 × 10(-6) for ALS and p = 4.3 × 10(-5) for PD). The odds ratio for any ANG variant in patients versus controls was 9.2 for ALS and 6.7 for PD. INTERPRETATION: The data from this multicenter study demonstrate that there is a strong association between PD, ALS, and ANG variants. ANG is a genetic link between ALS and PD.

23 Review Substantia nigra hyperechogenicity is a risk marker of Parkinson's disease: yes. 2011

Berg, Daniela. ·Department of Neurodegeneration, Hertie-Institute of Clinical Brain Research and German Center for Neurodegenerative Diseases (DZNE), University of Tuebingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany. daniela.berg@uni-tuebingen.de ·J Neural Transm (Vienna) · Pubmed #21207077.

ABSTRACT: As there is increasing evidence that the neurodegenerative process in Parkinson's disease (PD) starts years to decades before clinical symptoms allow diagnosis, markers for the identification of subjects at risk are eagerly sought after in order to allow an earlier, disease modulating or even neuroprotective therapy. In recent years, transcranial sonography (TCS) has evolved as a useful instrument in the differential diagnosis and also very early diagnosis of PD. The typical hallmark for PD, hyperechogenicity at the anatomical site of the substantia nigra (SN), can also be found in about 10% of healthy subjects. There is accumulating evidence that SN hyperechogenicity discloses a vulnerability of the nigrostriatal system in at least some of these persons. Moreover, an association of the ultrasound sign with a number of risk and premotor markers has been shown. However, the most striking argument for a relevance of SN hyperechogenicity in healthy subjects can be derived from the observation that some initially healthy subjects with SN hyperechogenicity developed PD in the long run, an observation which has led to longitudinal studies on the predictive value of the ultrasound sign for the development of PD. A first follow up after 3 years of a large cohort of at baseline extrapyramidally healthy individuals revealed a relative risk for incident PD 17.37 times higher in subjects with SN hyperechogenicity at baseline compared to those without this echomarker. Taken together, there is encouraging evidence to implement TCS in a screening battery to identify subjects at risk for the development of PD.

24 Review Hyperechogenicity of the substantia nigra: pitfalls in assessment and specificity for Parkinson's disease. 2011

Berg, Daniela. ·Hertie-Institute of Clinical Brain Research and German Center for Neurodegenerative Diseases, Department of Neurodegeneration, University of Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany. daniela.berg@uni-tuebingen.de ·J Neural Transm (Vienna) · Pubmed #20830493.

ABSTRACT: During the last decade, substantia nigra (SN) hyperechogenicity has been established as a valuable supplementary diagnostic marker for Parkinson's disease. As an increasing number of studies indicate that this ultrasound feature may even be evident before motor symptoms of Parkinson's disease occur, longitudinal studies revealing its value as a screening instrument for subjects at risk are awaited with great expectancy. At the same time, other studies have shown that SN hyperechogenicity is not only found in Parkinson's disease but also in other disease entities. Limitations and pitfalls of the method need to be considered to evaluate and compare these studies. Taking these into account, it is important to realize that in some other neurodegenerative diseases as well as in disorders associated with an increased risk for Parkinson's disease hyperechogenicity can be found--usually, however, less prevalent. Interestingly, even in subgroups of patients with non-neurodegenerative disorders, SN hyperechogenicity can be detected. This holds, for example, true for multiple sclerosis patients with a higher rate of disease progression. In this disorder, microglia activation is known to occur, which is also evident in Parkinson's disease. This pathomechanism as well as increased iron content is known to contribute to SN hyperechogenicity. From the studies published so far it can be concluded that, although SN hyperechogenicity is not only found in Parkinson's disease, assessment of the echogenicity of the SN and other ultrasound features is valuable in the differential diagnosis of Parkinsonian syndromes and most probably in subjects at risk. Further elucidation of the cause of the echosignal will not only contribute to the understanding of the pathophysiology of some neurodegenerative diseases but also to an even better implementation in the clinical routine and for scientific studies.

25 Review Transcranial sonography in the premotor diagnosis of Parkinson's disease. 2010

Behnke, Stefanie / Schröder, Ute / Berg, Daniela. ·Department of Neurology, University Hospital of the Saarland, Homburg/Saarland, Germany. ·Int Rev Neurobiol · Pubmed #20692496.

ABSTRACT: Substantia nigra hyperechogenicity (SN+) is a common finding in transcranial ultrasound studies of parkinsonian patients. However, this echofeature is also found in 10% of healthy controls and is here associated with PD risk factors such as male gender and positive family history for PD, as well as with putative premotor symptoms such as hyposmia, depression, sleep disturbances, and subtle neuropsychological and motor impairment. SN+ is hypothesized to indicate an increased risk to develop PD during lifetime. PET studies substantiate this hypothesis, given that SN+ controls showed reduced striatal [(18)Fluoro] Dopa uptake in PET studies. First results of longitudinal follow-up studies show a higher relative risk for future PD in SN+ asymptomatic individuals.

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