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Parkinson Disease: HELP
Articles from Tubingen
Based on 306 articles published since 2008
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These are the 306 published articles about Parkinson Disease that originated from Tubingen during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8 · 9 · 10 · 11 · 12 · 13
1 Editorial Advances in sensor and wearable technologies for Parkinson's disease. 2016

Sánchez-Ferro, Álvaro / Maetzler, Walter. ·HM CINAC, Hospital Universitario HM Puerta del Sur, Móstoles, Madrid, Spain. · Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. · Center for Neurology and Hertie Institute for Clinical Brain Research, Department of Neurodegeneration, University of Tübingen, Tübingen, Germany. walter.maetzler@uni-tuebingen.de. · German Center for Neurodegenerative Diseases, Tübingen, Germany. walter.maetzler@uni-tuebingen.de. ·Mov Disord · Pubmed #27477675.

ABSTRACT: -- No abstract --

2 Editorial Fruit flies, bile acids, and Parkinson disease: a mitochondrial connection? 2015

Greenamyre, J Timothy / Sanders, Laurie H / Gasser, Thomas. ·From the Pittsburgh Institute for Neurodegenerative Diseases and Department of Neurology (J.T.G., L.H.S.), University of Pittsburgh, PA · and the Department of Neurology and Department of Neurodegenerative Diseases (T.G.), Hertie Institute for Clinical Brain Research, University of Tübingen, Germany. ·Neurology · Pubmed #26253445.

ABSTRACT: -- No abstract --

3 Editorial Body-worn sensors--the brave new world of clinical measurement? 2015

Maetzler, Walter / Rochester, Lynn. ·Department of Neurodegeneration, Hertie Institute for Clinical Brain Research (HIH), University of Tuebingen, Tuebingen, Germany. · German Center for Neurodegenerative Diseases (DZNE), Tuebingen, Germany. · Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom. ·Mov Disord · Pubmed #26173577.

ABSTRACT: -- No abstract --

4 Editorial Parkinson disease GWAS: the question of lumping or splitting is back again. 2015

Simón-Sánchez, Javier / Gasser, Thomas. ·From Genetics and Epigenetics of Neurodegeneration (J.S.-S.) and Department of Neurodegenerative Diseases (T.G.), Hertie Institute for Clinical Brain Research, University of Tübingen · and German Center for Neurodegenerative Diseases (J.S.-S., T.G.), Tübingen, Germany. ·Neurology · Pubmed #25663226.

ABSTRACT: -- No abstract --

5 Editorial LRRK2 in Parkinson's disease - drawing the curtain of penetrance: a commentary. 2008

Krüger, Rejko. ·Laboratory of Functional Neurogenomics, Center of Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, Germany. rejko.krueger@uni-tuebingen.de ·BMC Med · Pubmed #18986509.

ABSTRACT: Parkinson's disease is the most common neurodegenerative movement disorder and affects about 2% of the population over the age of 60 years. In 2004, mutations in the LRRK2 gene were first described and turned out to be the most frequent genetic cause of familial and sporadic Parkinson's disease and may account for up to 40% of patients in distinct populations. Based on these findings, Latourelle and colleagues show that the penetrance of the most common LRRK2 mutation is higher in patients with familial compared with sporadic Parkinson's disease and identified a substantial number of affected relatives of mutation carriers not presenting with a LRRK2 mutation themselves. This commentary discusses the role of genetic and/or environmental susceptibility factors modulating the expressivity of the disease trait, how these factors may contribute to the phenomenon of phenocopies in genetically defined Parkinson's disease pedigrees, and how the findings of Latourelle and colleagues, published this month in BMC Medicine, relate to current concepts of genetic counselling.

6 Review Regulation of LRRK2: insights from structural and biochemical analysis. 2018

Gilsbach, Bernd K / Eckert, Marita / Gloeckner, Christian Johannes. ·DZNE-German Center for Neurodegenerative Diseases, Otfried-Müller Str. 23, D-72076 Tübingen, Germany. · University of Tübingen, Institute for Ophthalmic Research, Center for Ophthalmology, Elfriede-Aulhorn-Str. 7, D-72076 Tübingen, Germany. ·Biol Chem · Pubmed #29894291.

ABSTRACT: Leucine-rich repeat kinase 2 (LRRK2) is a multi-domain protein and its mutations can lead to Parkinson's disease. Recent studies on LRRK2 and homologue proteins have advanced our mechanistic understanding of LRRK2 regulation. Here, we summarize the available data on the biochemistry and structure of LRRK2 and postulate three possible layers of regulation, translocation, monomer-dimer equilibrium and intramolecular activation of domains.

7 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.

8 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.

9 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.

10 Review [Genetic risk variants in Parkinson's disease and other movement disorders]. 2017

Brockmann, K / Lohmann, K. ·Zentrum für Neurologie, Abteilung Neurodegeneration, Hertie-Institut für klinische Hirnforschung, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Universität Tübingen, Hoppe Seyler Straße 3, 72076, Tübingen, Deutschland. kathrin.brockmann@uni-tuebingen.de. · Institut für Neurogenetik, Universität zu Lübeck, Lübeck, Deutschland. ·Nervenarzt · Pubmed #28536875.

ABSTRACT: Movement disorders are often genetically complex with genetic risk factors playing a major role. For example, monogenic causes of Parkinson's disease (PD) can be found in only 2-5% of patients who often have an early onset (<40 years). In the majority of patients, common genetic variants seem to contribute to the disease risk. To date, 24 genetic risk factors have been identified. For restless legs syndrome (RLS), six different risk variants have been reported but no monogenic cause is known yet. For the genetic risk factors of essential tremor and dystonia, which are less well studied, only five and two candidate variants, respectively, have been described but their roles still require independent confirmation. In this review, we provide an overview on the involved genes, their function, and discuss possible, disease mechanism-driven therapies.

11 Review Classification of advanced stages of Parkinson's disease: translation into stratified treatments. 2017

Krüger, Rejko / Klucken, Jochen / Weiss, Daniel / Tönges, Lars / Kolber, Pierre / Unterecker, Stefan / Lorrain, Michael / Baas, Horst / Müller, Thomas / Riederer, Peter. ·Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-Sur-Alzette, Luxembourg. rejko.krueger@uni.lu. · Centre Hospitalier de Luxembourg (CHL), Luxembourg, Luxembourg. rejko.krueger@uni.lu. · Molecular Neurology, University of Erlangen, Erlangen, Germany. · Department for Neurodegenerative Diseases and Hertie-Institute for Clinical Brain Research, Center for Neurology, University of Tübingen, Tübingen, Germany. · Department of Neurology of the Ruhr-University Bochum at St Josef-Hospital, Gudrunstrasse 56, 44791 , Bochum, Germany. · Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-Sur-Alzette, Luxembourg. · Centre Hospitalier de Luxembourg (CHL), Luxembourg, Luxembourg. · Center of Mental Health, Clinic and Policlinic of Psychiatry, Psychosomatics and Psychotherapy, University Hospital, Würzburg, Germany. · Nervenarztpraxis Gerresheim, Düsseldorf, Germany. · Department of Neurology, Klinikum Hanau GmbH, Hanau, Germany. · Department of Neurology, St. Joseph Hospital Berlin-Weissensee, Berlin, Germany. ·J Neural Transm (Vienna) · Pubmed #28342083.

ABSTRACT: Advanced stages of Parkinson's disease (advPD) still impose a challenge in terms of classification and related stage-adapted treatment recommendations. Previous concepts that define advPD by certain milestones of motor disability apparently fall short in addressing the increasingly recognized complexity of motor and non-motor symptoms and do not allow to account for the clinical heterogeneity that require more personalized approaches. Therefore, deep phenotyping approaches are required to characterize the broad-scaled, continuous and multidimensional spectrum of disease-related motor and non-motor symptoms and their progression under real-life conditions. This will also facilitate the reasoning for clinical care and therapeutic decisions, as neurologists currently have to refer to clinical trials that provide guidance on a group level; however, this does not always account for the individual needs of patients. Here, we provide an overview on different classifications for advPD that translate into critical phenotypic patterns requiring the differential therapeutic adjustments. New concepts refer to precision medicine approaches also in PD and first studies on genetic stratification for therapeutic outcomes provide a potential for more objective treatment recommendations. We define novel treatment targets that align with this concept and make use of emerging device-based assessments of real-life information on PD symptoms. As these approaches require empowerment of patients and integration into treatment decisions, we present communication strategies and decision support based on new technologies to adjust treatment of advPD according to patient demands and safety.

12 Review [Helpful instrumental examinations in idiopathic Parkinson's disease]. 2017

Walter, U / Zach, H / Liepelt-Scarfone, I / Maetzler, W. ·Klinik und Poliklinik für Neurologie, Universitätsmedizin Rostock, Rostock, Deutschland. · Universitätsklinik für Neurologie, Medizinische Universität Wien, Wien, Österreich. · Donders Institute for Brain, Cognition and Behaviour, Department of Neurology, Radboud University Medical Centre, Nijmegen, Niederlande. · Hertie Institut für klinische Hirnforschung, Universität Tübingen und Deutsches Zentrum für Neurodegenerative Erkrankungen, Tübingen, Deutschland. · Klinik für Neurologie, Universitätsklinikum Schleswig-Holstein, Arnold-Heller-Straße 3, 24105, Kiel, Deutschland. w.maetzler@neurologie.uni-kiel.de. ·Nervenarzt · Pubmed #28289798.

ABSTRACT: BACKGROUND: The clinical diagnosis of idiopathic Parkinson's disease (iPD) can be challenging. In these cases, additional diagnostic methods are available that can help to improve diagnostic accuracy. OBJECTIVES, MATERIAL AND METHODS: This article provides an overview of currently available and promising novel ancillary methods for the early and differential diagnosis of iPD. RESULTS: Imaging tools, such as 1.5 Tesla magnetic resonance imaging (MRI) and computed tomography (CT) are mainly used for the differentiation between iPD and symptomatic parkinsonian syndromes (PS). High-resolution diffusion tensor imaging and iron and neuromelanin-sensitive high-field MRI sequences can become important in the future, particularly for earlier diagnosis. Transcranial B‑mode sonography of the substantia nigra and basal ganglia is established for early and differential diagnostics, especially in the combination of diagnostic markers but necessitates an adequately trained investigator and the use of validated digital image analysis instruments. DATScan can discriminate iPD from essential tremor, medication-induced parkinsonism and psychogenic movement disorder but not iPD from atypical PS. For the latter differential diagnosis, fluorodeoxyglucose positron emission tomography and myocardial metaiodobenzylguanidine scintigraphy can be helpful. Olfactory testing should preferably be used in combination with other diagnostic tests. Genetic, biochemical and histopathological tests are currently not recommended for routine use. Novel sensor-based techniques have a high potential to support clinical diagnosis of iPD but have not yet reached a developmental stage that is sufficient for clinical use. Novel sensor-based techniques have high potential to support clinical diagnosis of iPD, but have not yet reached a development stage that is sufficient for clinical use. CONCLUSION: Ancillary diagnostic methods can support the early and differential diagnosis of iPD.

13 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.

14 Review The Birth of the Modern Era of Parkinson's Disease Genetics. 2017

Singleton, Andrew B / Hardy, John A / Gasser, Thomas. ·Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA. · Department of Molecular Neuroscience, UCL Institute of Neurology, University College London, London, UK. · Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, and German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany. ·J Parkinsons Dis · Pubmed #28282818.

ABSTRACT: -- No abstract --

15 Review [Diagnostics of clinical and prodromal idiopathic Parkinson's disease : New criteria]. 2017

Zach, H / Walter, U / Liepelt-Scarfone, I / Maetzler, W. ·Universitätsklinik für Neurologie, Medizinische Universität Wien, Wien, Österreich. · Donders Institute for Brain, Cognition and Behaviour, Department of Neurology, Radboud University Medical Centre, Nijmegen, Niederlande. · Klinik und Poliklinik für Neurologie, Universitätsmedizin Rostock, Rostock, Deutschland. · Hertie Institut für klinische Hirnforschung, Universität Tübingen und Deutsches Zentrum für Neurodegenerative Erkrankungen, Tübingen, Deutschland. · Klinik für Neurologie, Universitätsklinikum Schleswig-Holstein, Arnold-Heller-Straße 3, 24105, Kiel, Deutschland. w.maetzler@neurologie.uni-kiel.de. ·Nervenarzt · Pubmed #28213756.

ABSTRACT: BACKGROUND: Recently, the Movement Disorder Society (MDS) published an adaptation of the previous United Kingdom Brain Bank Society (UKBBS) criteria for the diagnosis of idiopathic Parkinson's disease (iPD). OBJECTIVES: This article presents the changes in the current clinical diagnostic criteria for IPD. Furthermore, the new MDS criteria for prodromal iPD are discussed. RESULTS: The recently introduced MDS criteria for the clinical diagnosis of iPD include useful novel features (e.g. postural instability is no longer listed as a cardinal symptom, familiar history of iPD and intake of neuroleptics at the first visit no longer lead to exclusion of the diagnosis) and red flags do not lead to exclusion of the diagnosis; however, they must be counterbalanced by the presence of supportive criteria for iPD. The criteria for identification of persons in the prodromal stage are currently established only for scientific investigations. CONCLUSION: The new MDS criteria for the diagnostics of iPD should help to improve the sensitivity and specificity.

16 Review First model of dimeric LRRK2: the challenge of unrevealing the structure of a multidomain Parkinson's-associated protein. 2016

Guaitoli, Giambattista / Gilsbach, Bernd K / Raimondi, Francesco / Gloeckner, Christian Johannes. ·German Center for Neurodegenerative Diseases (DZNE), 72076 Tübingen, Germany. · Institute for Ophthalmic Research, Center for Ophthalmology, Eberhard Karls University, 72076 Tübingen, Germany. · Cell Networks, University of Heidelberg, 69120 Heidelberg, Germany. ·Biochem Soc Trans · Pubmed #27913672.

ABSTRACT: Mutations within the leucine-rich repeat kinase 2 (LRRK2) gene represent the most common cause of Mendelian forms of Parkinson's disease, among autosomal dominant cases. Its gene product, LRRK2, is a large multidomain protein that belongs to the Roco protein family exhibiting GTPase and kinase activity, with the latter activity increased by pathogenic mutations. To allow rational drug design against LRRK2 and to understand the cross-regulation of the G- and the kinase domain at a molecular level, it is key to solve the three-dimensional structure of the protein. We review here our recent successful approach to build the first structural model of dimeric LRRK2 by an integrative modeling approach.

17 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.

18 Review Speech outcomes in Parkinson's disease after subthalamic nucleus deep brain stimulation: A systematic review. 2016

Aldridge, Danielle / Theodoros, Deborah / Angwin, Anthony / Vogel, Adam P. ·School of Health and Rehabilitation Sciences, The University of Queensland, Brisbane, Australia; Asia Pacific Centre for Neuromodulation, Queensland Brain Institute, The University of Queensland, Brisbane, Australia. · School of Health and Rehabilitation Sciences, The University of Queensland, Brisbane, Australia. Electronic address: d.theodoros@uq.edu.au. · School of Health and Rehabilitation Sciences, The University of Queensland, Brisbane, Australia. · Centre for Neuroscience of Speech, The University of Melbourne, Melbourne, Australia; Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, University of Tübingen, Germany. ·Parkinsonism Relat Disord · Pubmed #27693195.

ABSTRACT: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is effective in reducing motor symptoms for many individuals with Parkinson's disease (PD). However, STN DBS does not appear to influence speech in the same way, and may result in a variety of negative outcomes for people with PD (PWP). A high degree of inter-individual variability amongst PWP regarding speech outcomes following STN DBS is evident in many studies. Furthermore, speech studies in PWP following STN DBS have employed a wide variety of designs and methodologies, which complicate comparison and interpretation of outcome data amongst studies within this growing body of research. An analysis of published evidence regarding speech outcomes in PWP following STN DBS, according to design and quality, is missing. This systematic review aimed to analyse and coalesce all of the current evidence reported within observational and experimental studies investigating the effects of STN DBS on speech. It will strengthen understanding of the relationship between STN DBS and speech, and inform future research by highlighting methodological limitations of current evidence.

19 Review New methods for the assessment of Parkinson's disease (2005 to 2015): A systematic review. 2016

Sánchez-Ferro, Álvaro / Elshehabi, Morad / Godinho, Catarina / Salkovic, Dina / Hobert, Markus A / Domingos, Josefa / van Uem, Janet Mt / Ferreira, Joaquim J / Maetzler, Walter. ·HM CINAC, Hospital Universitario HM Puerta del Sur, Móstoles, Madrid, Spain. asferro@mit.edu. · Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. asferro@mit.edu. · Center for Neurology and Hertie Institute for Clinical Brain Research (HIH), Department of Neurodegeneration, University of Tübingen, Tübingen, Germany. · DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany. · Clinical Pharmacology Unit, Instituto de Medicina Molecular, Lisbon, Portugal. · Center of Interdisciplinary Research Egas Moniz (CiiEM), Instituto Superior de Ciências da Saúde Egas Moniz, Monte de Caparica, Portugal. · CNS-Campus Neurológico Sénior, Torres Vedras, Portugal. · Laboratory of Clinical Pharmacology and Therapeutics, Faculty of Medicine, University of Lisbon, Portugal. ·Mov Disord · Pubmed #27430969.

ABSTRACT: BACKGROUND: The past decade has witnessed a highly dynamic and growing expansion of novel methods aimed at improving the assessment of Parkinson's disease with technology (NAM-PD) in laboratory, clinical, and home environments. However, the current state of NAM-PD regarding their maturity, feasibility, and usefulness in assessing the main PD features has not been systematically evaluated. METHODS: A systematic review of articles published in the field from 2005 to 2015 was performed. Of 9,503 publications identified in PubMed and the Web of Science, 848 full papers were evaluated, and 588 original articles were assessed to evaluate the technological, demographic, clinimetric, and technology transfer readiness parameters of NAM-PD. RESULTS: Of the studies, 65% included fewer than 30 patients, < 50% employed a standard methodology to validate diagnostic tests, 8% confirmed their results in a different dataset, and 87% occurred in a clinic or lab. The axial features domain was the most frequently studied, followed by bradykinesia. Rigidity and nonmotor domains were rarely investigated. Only 6% of the systems reached a technology level that justified the hope of being included in clinical assessments in a useful time period. CONCLUSIONS: This systematic evaluation provides an overview of the current options for quantitative assessment of PD and what can be expected in the near future. There is a particular need for standardized and collaborative studies to confirm the results of preliminary initiatives, assess domains that are currently underinvestigated, and better validate the existing and upcoming NAM-PD. © 2016 International Parkinson and Movement Disorder Society.

20 Review [Wearable Technique for the Assessment of Parkinson Symptoms: What's the Future?]. 2016

Maetzler, W / Krüger, R / Müller, T / Oertel, W / Urban, P / Warnecke, T / Klucken, J. ·Neurologie mit Schwerpunkt Neurodegeneration und Hertie Institut für klinische Hirnforschung, Universitätsklinikum Tübingen, Tübingen. · Klinik für Neurologie, St. Joseph Krankenhaus Berlin-Weißensee, Berlin. · Klinik für Neurologie, Universitätsklinikum Gießen und Marburg GmbH, Standort Marburg, Marburg. · Abteilung für Neurologie, Asklepios Klinik Barmbek, Hamburg. · Department für Neurologie, Universitätsklinikum Münster, Münster. · Molekulare Neurologie, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen. ·Fortschr Neurol Psychiatr · Pubmed #27276073.

ABSTRACT: Parkinson's disease (PD) is a multisystem disorder with a plethora of symptoms affecting the quality of life of patients in the home environment. Due to the rapid development of wearable technique in the health and fitness sector, an increasing number of such wearable devices are available to complement diagnostic strategies of PD symptoms not only in the clinical but also in the home environment. This development has clear advantages over clinical evaluation, as the latter is relatively subjective, time-consuming and costly, and provides only a snapshot of the condition. First results about the use of such technology for the assessment of PD symptoms (including bradykinesia, dyskinesia, tremor, daily activity and sleep behavior) in the home environment are promising. They suggest that these techniques can provide complementary information about the symptoms of PD patients, and have the potential to be included in future diagnostic workup concepts of routine care in PD. The use of such technique provides also the opportunity to more actively include patients into medical decision-making processes.

21 Review A clinical view on the development of technology-based tools in managing Parkinson's disease. 2016

Maetzler, Walter / Klucken, Jochen / Horne, Malcolm. ·Hertie Institute for Clinical Brain Research, Department of Neurodegeneration, Center of Neurology, University of Tuebingen, Tuebingen, Germany. walter.maetzler@uni-tuebingen.de. · DZNE, German Center for Neurodegenerative Diseases, Tuebingen, Germany. walter.maetzler@uni-tuebingen.de. · Department of Molecular Neurology, University Hospital Erlangen, Friedrich-Alexander-University (FAU) Erlangen-Nürnberg, Erlangen, Germany. · Florey Institute for Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia. · St. Vincent's, Neurology Department, Fitzroy, Victoria, Australia. ·Mov Disord · Pubmed #27273651.

ABSTRACT: Recently, quantitative, objective, and easy-to-use technology-based tools that can assess PD features over long time periods have been developed and generate clinically relevant and comparable patient information. Herein, we present a clinician's view on technological developments that have the potential to revolutionize clinical management concepts in PD. According to prominent examples in clinical medicine (e.g., blood glycosylated hemoglobin and blood pressure), we argue that the consideration of technology-based assessment in the clinical management of PD must be based on specific assumptions: (1) It provides a valid and accurate parameter of a clinically relevant feature of the disease; (2) there is confirmed evidence that the parameter has an ecologically relevant effect on the specific clinical application; (3) a target range can be defined wherein the parameter reflects the adequate treatment response; and (4) implementation is simple to allow repetitive use. Currently, there are no technology-based tools available that fulfil all these assumptions; however, assessments of akinesia, dyskinesia, motor fluctuations, physical inactivity, gait impairment, and postural instability seem relatively close to the specifications described. An iterative process of integration is recommended to bring technology-based tools into clinical practice. © 2016 International Parkinson and Movement Disorder Society.

22 Review Technology in Parkinson's disease: Challenges and opportunities. 2016

Espay, Alberto J / Bonato, Paolo / Nahab, Fatta B / Maetzler, Walter / Dean, John M / Klucken, Jochen / Eskofier, Bjoern M / Merola, Aristide / Horak, Fay / Lang, Anthony E / Reilmann, Ralf / Giuffrida, Joe / Nieuwboer, Alice / Horne, Malcolm / Little, Max A / Litvan, Irene / Simuni, Tanya / Dorsey, E Ray / Burack, Michelle A / Kubota, Ken / Kamondi, Anita / Godinho, Catarina / Daneault, Jean-Francois / Mitsi, Georgia / Krinke, Lothar / Hausdorff, Jeffery M / Bloem, Bastiaan R / Papapetropoulos, Spyros / Anonymous1111027. ·James J. and Joan A. Gardner Family Center for Parkinson's disease and Movement Disorders, University of Cincinnati, Cincinnati, Ohio, USA. alberto.espay@uc.edu. · Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, Massachusetts, USA. · Department of Neurosciences, University of California San Diego, La Jolla, CA, USA. · Department of Neurodegeneration, Hertie Institute for Clinical Brain Research (HIH), University of Tuebingen, Tübingen, Germany. · DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany. · Davis Phinney Foundation for Parkinson's, Boulder, Colorado, USA. · Department of Molecular Neurology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany. · Digital Sports Group, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany. · Department of Neuroscience "Rita Levi Montalcini", Città della salute e della scienza di Torino, Torino, Italy. · Department of Neurology, Oregon Health & Science University, Portland VA Medical System, Portland, Oregon. · APDM, Inc., Portland, Oregon, USA. · Morton and Gloria Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, Toronto, Canada. · George-Huntington-Institute, Muenster, Germany. · Department of Radiology, University of Muenster, Muenster, Germany. · Department of Neurodegenerative Diseases and Hertie-Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany. · Great Lakes NeuroTechnologies, Cleveland, Ohio, USA. · Neuromotor Rehabilitation Research Group, Department of Rehabilitation Sciences, KU Leuven, Leuven, Belgium. · Global Kinetics Corporation & Florey Institute for Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia. · Department of Mathematics, Aston University, Birmingham, UK. · Media Lab, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. · Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA. · Department of Neurology, University of Rochester Medical Center, Rochester, New York, USA. · Michael J Fox Foundation for Parkinson's Research, New York City, New York, USA. · Department of Neurology, National Institute of Clinical Neurosciences, Budapest, Hungary. · Center of Interdisciplinary Research Egas Moniz (CiiEM), Instituto Superior de Ciências da Saúde Egas Moniz, Monte de Caparica, Portugal. · Apptomics LLC, Wellesley, Massachusetts, USA. · Medtronic Neuromodulation, Minneapolis, Minnesota, USA. · Sackler School of Medicine, Tel Aviv University and Center for the Study of Movement, Cognition, and Mobility, Neurological Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. · Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Department of Neurology, Nijmegen, the Netherlands. · Massachusetts General Hospital, Boston, Massachusetts, USA. ·Mov Disord · Pubmed #27125836.

ABSTRACT: The miniaturization, sophistication, proliferation, and accessibility of technologies are enabling the capture of more and previously inaccessible phenomena in Parkinson's disease (PD). However, more information has not translated into a greater understanding of disease complexity to satisfy diagnostic and therapeutic needs. Challenges include noncompatible technology platforms, the need for wide-scale and long-term deployment of sensor technology (among vulnerable elderly patients in particular), and the gap between the "big data" acquired with sensitive measurement technologies and their limited clinical application. Major opportunities could be realized if new technologies are developed as part of open-source and/or open-hardware platforms that enable multichannel data capture sensitive to the broad range of motor and nonmotor problems that characterize PD and are adaptable into self-adjusting, individualized treatment delivery systems. The International Parkinson and Movement Disorders Society Task Force on Technology is entrusted to convene engineers, clinicians, researchers, and patients to promote the development of integrated measurement and closed-loop therapeutic systems with high patient adherence that also serve to (1) encourage the adoption of clinico-pathophysiologic phenotyping and early detection of critical disease milestones, (2) enhance the tailoring of symptomatic therapy, (3) improve subgroup targeting of patients for future testing of disease-modifying treatments, and (4) identify objective biomarkers to improve the longitudinal tracking of impairments in clinical care and research. This article summarizes the work carried out by the task force toward identifying challenges and opportunities in the development of technologies with potential for improving the clinical management and the quality of life of individuals with PD. © 2016 International Parkinson and Movement Disorder Society.

23 Review Genetics in Parkinson disease: Mendelian versus non-Mendelian inheritance. 2016

Hernandez, Dena G / Reed, Xylena / Singleton, Andrew B. ·Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA. · German Center for Neurodegenerative Diseases (DZNE)-Tübingen, Tübingen, Germany. · Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA. singleta@mail.nih.gov. ·J Neurochem · Pubmed #27090875.

ABSTRACT: Parkinson's disease is a common, progressive neurodegenerative disorder, affecting 3% of those older than 75 years of age. Clinically, Parkinson's disease (PD) is associated with resting tremor, postural instability, rigidity, bradykinesia, and a good response to levodopa therapy. Over the last 15 years, numerous studies have confirmed that genetic factors contribute to the complex pathogenesis of PD. Highly penetrant mutations producing rare, monogenic forms of the disease have been discovered in singular genes such as SNCA, Parkin, DJ-1, PINK 1, LRRK2, and VPS35. Unique variants with incomplete penetrance in LRRK2 and GBA have been shown to be strong risk factors for PD in certain populations. Additionally, over 20 common variants with small effect sizes are now recognized to modulate the risk for PD. Investigating Mendelian forms of PD has provided precious insight into the pathophysiology that underlies the more common idiopathic form of disease; however, no treatment methodologies have developed. Furthermore, for identified common risk alleles, the functional basis underlying risk principally remains unknown. The challenge over the next decade will be to strengthen the findings delivered through genetic discovery by assessing the direct, biological consequences of risk variants in tandem with additional high-content, integrated datasets. This review discusses monogenic risk factors and mechanisms of Mendelian inheritance of Parkinson disease. Highly penetrant mutations in SNCA, Parkin, DJ-1, PINK 1, LRRK2 and VPS35 produce rare, monogenic forms of the disease, while unique variants within LRRK2 and GBA show incomplete penetrance and are strong risk factors for PD. Additionally, over 20 common variants with small effect sizes modulate disease risk. The challenge over the next decade is to strengthen genetic findings by assessing direct, biological consequences of risk variants in tandem with high-content, integrated datasets. This article is part of a special issue on Parkinson disease.

24 Review A Viewpoint on Wearable Technology-Enabled Measurement of Wellbeing and Health-Related Quality of Life in Parkinson's Disease. 2016

van Uem, Janet M T / Isaacs, Tom / Lewin, Alan / Bresolin, Eros / Salkovic, Dina / Espay, Alberto J / Matthews, Helen / Maetzler, Walter. ·Hertie Institute for Clinical Brain Research, Department of Neurodegeneration, Center of Neurology, University of Tuebingen, Tuebingen, Germany. · DZNE, German Center for Neurodegenerative Diseases, Tuebingen, Germany. · The Cure Parkinson's Trust, London, UK. · Gardner Center for Parkinson's disease and Movement Disorders, University of Cincinnati, Cincinnati, Ohio, USA. ·J Parkinsons Dis · Pubmed #27003779.

ABSTRACT: In this viewpoint, we discuss how several aspects of Parkinson's disease (PD) - known to be correlated with wellbeing and health-related quality of life-could be measured using wearable devices ('wearables'). Moreover, three people with PD (PwP) having exhaustive experience with using such devices write about their personal understanding of wellbeing and health-related quality of life, building a bridge between the true needs defined by PwP and the available methods of data collection. Rapidly evolving new technologies develop wearables that probe function and behaviour in domestic environments of people with chronic conditions such as PD and have the potential to serve their needs. Gathered data can serve to inform patient-driven management changes, enabling greater control by PwP and enhancing likelihood of improvements in wellbeing and health-related quality of life. Data can also be used to quantify wellbeing and health-related quality of life. Additionally these techniques can uncover novel more sensitive and more ecologically valid disease-related endpoints. Active involvement of PwP in data collection and interpretation stands to provide personally and clinically meaningful endpoints and milestones to inform advances in research and relevance of translational efforts in PD.

25 Review A systematic review of the characteristics and validity of monitoring technologies to assess Parkinson's disease. 2016

Godinho, Catarina / Domingos, Josefa / Cunha, Guilherme / Santos, Ana T / Fernandes, Ricardo M / Abreu, Daisy / Gonçalves, Nilza / Matthews, Helen / Isaacs, Tom / Duffen, Joy / Al-Jawad, Ahmed / Larsen, Frank / Serrano, Artur / Weber, Peter / Thoms, Andrea / Sollinger, Stefan / Graessner, Holm / Maetzler, Walter / Ferreira, Joaquim J. ·Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028, Lisboa, Portugal. · Center for Interdisciplinary Research Egas Moniz (CiiEM), Instituto Superior de Ciências da Saúde Egas Moniz, Monte de Caparica, Portugal. · CNS-Campus Neurológico Sénior, Torres Vedras, Portugal. · Laboratory of Clinical Pharmacology and Therapeutics, Faculty of Medicine, University of Lisbon, Lisbon, Portugal. · The Cure Parkinson's Trust, London, UK. · HSG-IMIT, Villingen-Schwenningen, Germany. · Norwegian Centre for Telemedicine, Tromso, Norway. · Hasomed GmbH, Magdeburg, Germany. · AbilityNet, London, UK. · Institute for Medical Genetics and Applied Genomics, University of Tuebingen, Tuebingen, Germany. · Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, Center of Neurology, University of Tuebingen, Tuebingen, Germany. · Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028, Lisboa, Portugal. joaquimjferreira@gmail.com. · Laboratory of Clinical Pharmacology and Therapeutics, Faculty of Medicine, University of Lisbon, Lisbon, Portugal. joaquimjferreira@gmail.com. · CNS-Campus Neurológico Sénior, Torres Vedras, Portugal. joaquimjferreira@gmail.com. ·J Neuroeng Rehabil · Pubmed #26969628.

ABSTRACT: BACKGROUND: There is growing interest in having objective assessment of health-related outcomes using technology-based devices that provide unbiased measurements which can be used in clinical practice and scientific research. Many studies have investigated the clinical manifestations of Parkinson's disease using such devices. However, clinimetric properties and clinical validation vary among the different devices. METHODS: Given such heterogeneity, we sought to perform a systematic review in order to (i) list, (ii) compare and (iii) classify technological-based devices used to measure motor function in individuals with Parkinson's disease into three groups, namely wearable, non-wearable and hybrid devices. A systematic literature search of the PubMed database resulted in the inclusion of 168 studies. These studies were grouped based on the type of device used. For each device we reviewed availability, use, reliability, validity, and sensitivity to change. The devices were then classified as (i) 'recommended', (ii) 'suggested' or (iii) 'listed' based on the following criteria: (1) used in the assessment of Parkinson's disease (yes/no), (2) used in published studies by people other than the developers (yes/no), and (3) successful clinimetric testing (yes/no). RESULTS: Seventy-three devices were identified, 22 were wearable, 38 were non-wearable, and 13 were hybrid devices. In accordance with our classification method, 9 devices were 'recommended', 34 devices were 'suggested', and 30 devices were classified as 'listed'. Within the wearable devices group, the Mobility Lab sensors from Ambulatory Parkinson's Disease Monitoring (APDM), Physilog®, StepWatch 3, TriTrac RT3 Triaxial accelerometer, McRoberts DynaPort, and Axivity (AX3) were classified as 'recommended'. Within the non-wearable devices group, the Nintendo Wii Balance Board and GAITRite® gait analysis system were classified as 'recommended'. Within the hybrid devices group only the Kinesia® system was classified as 'recommended'.

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