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Parkinson Disease: HELP
Articles from Medizinische Universitat Innsbruck
Based on 133 articles published since 2008
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These are the 133 published articles about Parkinson Disease that originated from Medizinische Universitat Innsbruck during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6
1 Guideline Collective physician perspectives on non-oral medication approaches for the management of clinically relevant unresolved issues in Parkinson's disease: Consensus from an international survey and discussion program. 2015

Odin, P / Ray Chaudhuri, K / Slevin, J T / Volkmann, J / Dietrichs, E / Martinez-Martin, P / Krauss, J K / Henriksen, T / Katzenschlager, R / Antonini, A / Rascol, O / Poewe, W / Anonymous2260838. ·Department of Neurology, Lund University Hospital, 221 85 Lund, Sweden; Klinikum-Bremerhaven, D-27574 Bremerhaven, Germany. Electronic address: per.odin@med.lu.se. · King's College London, and National Parkinson Foundation Centre of Excellence, Dept of Neurology, King's College Hospital, London, UK. · Department of Neurology, University of Kentucky College of Medicine, Kentucky Clinic L-445, 740 South Limestone Street, Lexington, KY 40536-0284, USA. · Department of Neurology, University Hospital of Würzburg, 97080 Würzburg, Germany. · Department of Neurology, Oslo University Hospital and University of Oslo, N-0424 Oslo, Norway. · National Center for Epidemiology and CIBERNED, ISCIII, Avenida Monforte de Lemos 5, 28029 Madrid, Spain. · Department of Neurosurgery, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. · University Hospital of Bispebjerg, Bispebjerg Bakke 23, 2400 København, NV, Denmark. · Department of Neurology and Karl Landsteiner Institute for Neuroimmunological and Neurodegenerative Disorders, Sozialmedizinisches Zentrum Ost - Donauspital, 1220 Wien Langobardenstraße 122, Austria. · Parkinson and Movement Disorders Unit, IRCCS Hospital San Camillo, Venice, Italy. · Clinical Investigation Center 1436 and Department of Clinical Pharmacology, INSERM and University Hospital of Toulouse, Toulouse University, 37 alées Jules Giesde, 31000 Toulouse, France; Clinical Investigation Center 1436 and Department of Neurosciences, INSERM and University Hospital of Toulouse, Toulouse University, 37 alées Jules Giesde, 31000 Toulouse, France. · Innsbruck Medical University/University Hospital, Anichstrasse 35, A-6020 Innsbruck, Austria. ·Parkinsonism Relat Disord · Pubmed #26233582.

ABSTRACT: Navigate PD was an educational program established to supplement existing guidelines and provide recommendations on the management of Parkinson's disease (PD) refractory to oral/transdermal therapies. It involved 103 experts from 13 countries overseen by an International Steering Committee (ISC) of 13 movement disorder specialists. The ISC identified 71 clinical questions important for device-aided management of PD. Fifty-six experts responded to a web-based survey, rating 15 questions as 'critically important;' these were refined to 10 questions by the ISC to be addressed through available evidence and expert opinion. Draft guidance was presented at international/national meetings and revised based on feedback. Key take-home points are: • Patients requiring levodopa >5 times daily who have severe, troublesome 'off' periods (>1-2 h/day) despite optimal oral/transdermal levodopa or non-levodopa-based therapies should be referred for specialist assessment even if disease duration is <4 years. • Cognitive decline related to non-motor fluctuations is an indication for device-aided therapies. If cognitive impairment is mild, use deep brain stimulation (DBS) with caution. For patients who have cognitive impairment or dementia, intrajejunal levodopa infusion is considered as both therapeutic and palliative in some countries. Falls are linked to cognitive decline and are likely to become more frequent with device-aided therapies. • Insufficient control of motor complications (or drug-resistant tremor in the case of DBS) are indications for device-aided therapies. Levodopa-carbidopa intestinal gel infusions or subcutaneous apomorphine pump may be considered for patients aged >70 years who have mild or moderate cognitive impairment, severe depression or other contraindications to DBS.

2 Editorial Diagnosis of PSP-P: Can a newly developed MRPI make the difference? 2018

Krismer, Florian / Seppi, Klaus. ·Department of Neurology, Medical University Innsbruck, Innsbruck, Austria. · Department of Neurology, Medical University Innsbruck, Innsbruck, Austria; Neuroimaging Research Core Facility, Medical University Innsbruck, Innsbruck, Austria. Electronic address: klaus.seppi@tirol-kliniken.at. ·Parkinsonism Relat Disord · Pubmed #30236828.

ABSTRACT: -- No abstract --

3 Editorial Eldad Melamed 1942-2015: Ave atque--A memorial. 2016

Olanow, C Warren / Poewe, Werner. ·Department of Neurology, Mount Sinai School of Medicine, New York, New York, USA. · Medical University Innsbruck, Innsbruck, Austria. ·Mov Disord · Pubmed #26685050.

ABSTRACT: -- No abstract --

4 Editorial Preface. 2015

Poewe, Werner / Goetz, Christopher G. ·Innsbruck Medical University, Austria. · Rush University Medical Center, Chicago, Illinois. ·Mov Disord · Pubmed #26301896.

ABSTRACT: -- No abstract --

5 Review Diffusion-weighted MRI distinguishes Parkinson disease from the parkinsonian variant of multiple system atrophy: A systematic review and meta-analysis. 2017

Bajaj, Sweta / Krismer, Florian / Palma, Jose-Alberto / Wenning, Gregor K / Kaufmann, Horacio / Poewe, Werner / Seppi, Klaus. ·Department of Neurology, Medical University Innsbruck, Innsbruck, Austria. · Dysautonomia Center, Department of Neurology, New York University School of Medicine, New York, New York, United States of America. · Neuroimaging Research Core Facility, Medical University Innsbruck, Innsbruck, Austria. ·PLoS One · Pubmed #29287113.

ABSTRACT: BACKGROUND: Putaminal diffusivity in brain magnetic resonance diffusion-weighted imaging (DWI) is increased in patients with the parkinsonian variant of multiple system atrophy (MSA-P) compared to Parkinson disease (PD) patients. PURPOSE: We performed a systematic review and meta-analysis to evaluate the diagnostic accuracy of DWI to distinguish MSA-P from PD. METHODS: Studies on DWI were identified through a systematic PubMed and Clarivate Analytics® Web of Science® Core Collection search. Papers were selected based on stringent inclusion criteria; minimum requirement was the inclusion of MSA-P and PD patients and documented true positive, true negative, false positive and false negative rates or overall sample size and reported sensitivity and specificity. Meta-analysis was performed using the hierarchical summary receiver operating characteristics curve approach. RESULTS: The database search yielded 1678 results of which 9 studies were deemed relevant. Diagnostic accuracy of putaminal diffusivity measurements were reported in all of these 9 studies, whereas results of other regions of interest were only reported irregularly. Therefore, a meta-analysis could only be performed for putaminal diffusivity measurements: 127 patients with MSA-P, 262 patients with PD and 70 healthy controls were included in the quantitative synthesis. The meta-analysis showed an overall sensitivity of 90% (95% confidence interval (CI): 76.7%-95.8%) and an overall specificity of 93% (95% CI: 80.0%-97.7%) to distinguish MSA-P from PD based on putaminal diffusivity. CONCLUSION: Putaminal diffusivity yields high sensitivity and specificity to distinguish clinically diagnosed patients with MSA-P from PD. The confidence intervals indicate substantial variability. Further multicenter studies with harmonized protocols are warranted particularly in early disease stages when clinical diagnosis is less certain.

6 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.

7 Review Nonmotor fluctuations: phenotypes, pathophysiology, management, and open issues. 2017

Classen, Joseph / Koschel, Jiri / Oehlwein, Christian / Seppi, Klaus / Urban, Peter / Winkler, Christian / Wüllner, Ullrich / Storch, Alexander. ·Department of Neurology, University of Leipzig, 04103, Leipzig, Germany. joseph.classen@medizin.uni-leipzig.de. · Parkinson-Klinik Ortenau, 77709, Wolfach, Germany. · , Lasurstr. 27, 07551, Gera, Germany. · Department of Neurology, Medical University Innsbruck and Neuroimaging Research Core Facility, Medical University Innsbruck, Innsbruck, Austria. · Department of Neurology, Asklepios Klinik Barmbek, 22291, Hamburg, Germany. · Department of Neurology, Lindenbrunn Hospital, 31863, Coppenbrügge, Germany. · Department of Neurology, University of Bonn, 53127, Bonn, Germany. · German Centre for Neurodegenerative Diseases (DZNE) Rostock, 18147, Rostock, Germany. · Department of Neurology, University of Rostock, 18147, Rostock, Germany. ·J Neural Transm (Vienna) · Pubmed #28702850.

ABSTRACT: Parkinson's disease (PD) is a neurodegenerative multisystem disorder characterized by progressive motor symptoms such as bradykinesia, tremor and muscle rigidity. Over the course of the disease, numerous non-motor symptoms, sometimes preceding the onset of motor symptoms, significantly impair patients' quality of life. The significance of non-motor symptoms may outweigh the burden through progressive motor incapacity, especially in later stages of the disease. The advanced stage of the disease is characterized by motor complications such as fluctuations and dyskinesias induced by the long-term application of levodopa therapy. In recent years, it became evident that various non-motor symptoms such as psychiatric symptoms, fatigue and pain also show fluctuations after chronic levodopa therapy (named non-motor fluctuations or NMFs). Although NMFs have moved into the focus of interest, current national guidelines on the treatment of PD may refer to non-motor symptoms and their management, but do not mention NMF, and do not contain recommendations on their management. The present article summarizes major issues related to NMF including clinical phenomenology and pathophysiology, and outlines a number of open issues and topics for future research.

8 Review Opicapone for the management of end-of-dose motor fluctuations in patients with Parkinson's disease treated with L-DOPA. 2017

Lees, Andrew J / Ferreira, Joaquim / Rascol, Olivier / Reichmann, Heinz / Stocchi, Fabrizio / Tolosa, Eduardo / Poewe, Werner. ·a Reta Lila Weston Institute for Neurological Studies, UCL , London , UK. · b Centro de Estudos Egas Moniz , Hospital de Santa Maria , Lisbon , Portugal. · c Departments of Clinical Pharmacology and Neurosciences, Clinical Investigation Center CIC 1436, NS-Park/FCRIN network and NeuroToul COEN Center , INSERM, Toulouse University Hospital and Toulouse3 University , Toulouse , France. · d Department of Neurology , Technische Universitaet Dresden , Dresden , Germany. · e Institute of Neurology , IRCCS San Raffaele Pisana , Rome , Italy. · f Neurology Service, Centro de Investigación Biomódica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Hospital Clínic, IDIBAPS , Universitat de Barcelona , Barcelona , Spain ​​​​. · g Department of Neurology , Innsbruck Medical University , Innsbruck , Austria. ·Expert Rev Neurother · Pubmed #28580819.

ABSTRACT: INTRODUCTION: Opicapone is a third generation, highly potent and effective catechol O‑methyltransferase (COMT) inhibitor that optimizes the pharmacokinetics and bioavailability of L-DOPA therapy. Areas covered: In this review, the authors describe the preclinical and clinical development of opicapone. In PD patients with motor fluctuations, once daily opicapone administration was well-tolerated and consistently reduced OFF-time and increased ON-time without increasing the frequency of troublesome dyskinesia, and these benefits were maintained over at least a year of continued open-label therapy. Expert commentary: With its convenient once-daily regimen, adjunct opicapone should be considered as an effective option for use in L-DOPA treated PD patients experiencing motor fluctuations.

9 Review Magnetic resonance imaging for the diagnosis of Parkinson's disease. 2017

Heim, Beatrice / Krismer, Florian / De Marzi, Roberto / Seppi, Klaus. ·Department of Neurology, Medical University of Innsbruck, Anichstraße 35, 6020, Innsbruck, Austria. · Department of Neurology, Medical University of Innsbruck, Anichstraße 35, 6020, Innsbruck, Austria. florian.krismer@i-med.ac.at. · Department of Neurology, Medical University of Innsbruck, Anichstraße 35, 6020, Innsbruck, Austria. Klaus.Seppi@tirol-kliniken.at. · Neuroimaging Research Core Facility, Medical University Innsbruck, Innsbruck, Austria. Klaus.Seppi@tirol-kliniken.at. ·J Neural Transm (Vienna) · Pubmed #28378231.

ABSTRACT: The differential diagnosis of parkinsonian syndromes is considered one of the most challenging in neurology and error rates in the clinical diagnosis can be high even at specialized centres. Despite several limitations, magnetic resonance imaging (MRI) has undoubtedly enhanced the diagnostic accuracy in the differential diagnosis of neurodegenerative parkinsonism over the last three decades. This review aims to summarize research findings regarding the value of the different MRI techniques, including advanced sequences at high- and ultra-high-field MRI and modern image analysis algorithms, in the diagnostic work-up of Parkinson's disease. This includes not only the exclusion of alternative diagnoses for Parkinson's disease such as symptomatic parkinsonism and atypical parkinsonism, but also the diagnosis of early, new onset, and even prodromal Parkinson's disease.

10 Review Parkinson disease. 2017

Poewe, Werner / Seppi, Klaus / Tanner, Caroline M / Halliday, Glenda M / Brundin, Patrik / Volkmann, Jens / Schrag, Anette-Eleonore / Lang, Anthony E. ·Department of Neurology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria. · Parkinson's Disease Research Education and Clinical Center, San Francisco Veteran's Affairs Medical Center, San Francisco, California, USA. · Department of Neurology, University of California - San Francisco, San Francisco, California, USA. · Brain and Mind Centre, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia. · Faculty of Medicine, University of New South Wales &Neuroscience Research Australia, Sydney, New South Wales, Australia. · Van Andel Research Institute, Center for Neurodegenerative Science, Grand Rapids, Michigan, USA. · Department of Neurology, University Hospital of Würzburg, Würzburg, Germany. · Department of Clinical Neuroscience, UCL Institute of Neurology, London, UK. · Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada. ·Nat Rev Dis Primers · Pubmed #28332488.

ABSTRACT: Parkinson disease is the second-most common neurodegenerative disorder that affects 2-3% of the population ≥65 years of age. Neuronal loss in the substantia nigra, which causes striatal dopamine deficiency, and intracellular inclusions containing aggregates of α-synuclein are the neuropathological hallmarks of Parkinson disease. Multiple other cell types throughout the central and peripheral autonomic nervous system are also involved, probably from early disease onwards. Although clinical diagnosis relies on the presence of bradykinesia and other cardinal motor features, Parkinson disease is associated with many non-motor symptoms that add to overall disability. The underlying molecular pathogenesis involves multiple pathways and mechanisms: α-synuclein proteostasis, mitochondrial function, oxidative stress, calcium homeostasis, axonal transport and neuroinflammation. Recent research into diagnostic biomarkers has taken advantage of neuroimaging in which several modalities, including PET, single-photon emission CT (SPECT) and novel MRI techniques, have been shown to aid early and differential diagnosis. Treatment of Parkinson disease is anchored on pharmacological substitution of striatal dopamine, in addition to non-dopaminergic approaches to address both motor and non-motor symptoms and deep brain stimulation for those developing intractable L-DOPA-related motor complications. Experimental therapies have tried to restore striatal dopamine by gene-based and cell-based approaches, and most recently, aggregation and cellular transport of α-synuclein have become therapeutic targets. One of the greatest current challenges is to identify markers for prodromal disease stages, which would allow novel disease-modifying therapies to be started earlier.

11 Review Ocular and visual disorders in Parkinson's disease: Common but frequently overlooked. 2017

Ekker, Merel S / Janssen, Sabine / Seppi, Klaus / Poewe, Werner / de Vries, Nienke M / Theelen, Thomas / Nonnekes, Jorik / Bloem, Bastiaan R. ·Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Department of Neurology, Nijmegen, The Netherlands. · Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Department of Neurology, Nijmegen, The Netherlands; University of Twente, MIRA Institute for Biomedical Technology and Technical Medicine, Biomedical Signal and Systems Group, Enschede, The Netherlands. Electronic address: sabineneuro.janssen@radboudumc.nl. · Medizinische Universität Innsbruck, Department of Neurology, Innsbruck, Austria. · Radboud University Medical Centre, Department of Ophthalmology, Nijmegen, The Netherlands. · Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Department of Rehabilitation, Nijmegen, The Netherlands. ·Parkinsonism Relat Disord · Pubmed #28284903.

ABSTRACT: Patients with Parkinson's disease (PD) often compensate for their motor deficits by guiding their movements visually. A wide range of ocular and visual disorders threatens the patients' ability to benefit optimally from visual feedback. These disorders are common in patients with PD, yet they have received little attention in both research and clinical practice, leading to unnecessary - but possibly treatable - disability. Based on a literature search covering 50 years, we review the range of ocular and visual disorders in patients with PD, and classify these according to anatomical structures of the visual pathway. We discuss six common disorders in more detail: dry eyes; diplopia; glaucoma and glaucoma-like visual problems; impaired contrast and colour vision; visuospatial and visuoperceptual impairments; and visual hallucinations. In addition, we review the effects of PD-related pharmacological and surgical treatments on visual function, and we offer practical recommendations for clinical management. Greater awareness and early recognition of ocular and visual problems in PD might enable timely instalment of tailored treatments, leading to improved patient safety, greater independence, and better quality of life.

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

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

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

13 Review Phenomenology and epidemiology of impulsive-compulsive behaviours in Parkinson's disease, atypical Parkinsonian disorders and non-Parkinsonian populations. 2017

Maloney, Eimer M / Djamshidian, Atbin / O'Sullivan, Sean S. ·Department of Neurology, Cork University Hospital, Ireland. Electronic address: eimer.maloney@hse.ie. · Department of Neurology, Medical University Innsbruck, Austria. · Department of Neurology, Cork University Hospital, Ireland; University College Cork, Ireland. ·J Neurol Sci · Pubmed #28108021.

ABSTRACT: Impulsive-compulsive behaviours are common, quality of life affecting consequences of dopamine replacement therapy which are well recognized in patients with idiopathic Parkinson's disease. Details of the occurrence and nature of these disorders in the atypical parkinsonian neurodegenerative disorders, and in non-Parkinson's patients prescribed dopaminergic stimulation for other disease processes, are slowly emerging. Here we review what is known about the phenomenology, epidemiology and risk factors for impulsive-compulsive behaviours in Parkinson's disease and in other, less well studied, patient groups. By analyzing the available published data, this review identifies potential clues as to the underlying neurobiological mechanism of these disorders, and further identifies critical gaps yet to be addressed.

14 Review Apomorphine and levodopa in Parkinson's disease: Two revolutionary drugs from the 1950's. 2016

Djamshidian, Atbin / Poewe, Werner. ·Medical University Innsbruck, Department of Neurology, Innsbruck, Austria. · Medical University Innsbruck, Department of Neurology, Innsbruck, Austria. Electronic address: werner.poewe@i-med.ac.at. ·Parkinsonism Relat Disord · Pubmed #28012951.

ABSTRACT: This article reviews the history of apomorphine and levodopa, which were both discovered in the 1950's and have revolutionized treatment paradigms of Parkinson's disease. Although the discovery of levodopa is a prime example of successful translation of basic neuroscience into clinical routine, the history of apomorphine was based on less solid evidence. Despite this, both drugs are, more than 6 decades after the first clinical experiments, still the two most efficacious medications to treat patients with Parkinson's disease. New and promising delivery strategies for both levodopa and apomorphine are currently under investigation to further improve clinical responses.

15 Review Prodromal Parkinson's disease as defined per MDS research criteria in the general elderly community. 2016

Mahlknecht, Philipp / Gasperi, Arno / Willeit, Peter / Kiechl, Stefan / Stockner, Heike / Willeit, Johann / Rungger, Gregorio / Sawires, Martin / Nocker, Michael / Rastner, Verena / Mair, Katherina J / Hotter, Anna / Poewe, Werner / Seppi, Klaus. ·Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. · Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London, United Kingdom. · Department of Neurology, Hospital of Bruneck, Bruneck, Italy. · King's British Heart Foundation Centre, King's College London, London, United Kingdom. · Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. · Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. Werner.Poewe@i-med.ac.at. · Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. Klaus.Seppi@tirol-kliniken.at. ·Mov Disord · Pubmed #27273736.

ABSTRACT: BACKGROUND: Recently, the International Parkinson and Movement Disorder Society has defined research criteria for prodromal Parkinson's disease (PD), but to date their predictive value has not yet been tested in population-based cohorts. METHODS: We retrospectively applied these criteria to the longitudinal Bruneck Study cohort aged 55-94 years using recorded data on all included risk and prodromal markers that are quick and easily assessable. RESULTS: After excluding participants with idiopathic PD or secondary parkinsonism, prevalence of probable prodromal PD in the remaining 539 participants was 2.2% (95% confidence interval, 1.2%-3.9%). Of 488 participants followed up over 5 years, 11 developed incident PD. Sensitivity of "probable prodromal PD" status for incident PD was 54.6% (95% confidence interval, 28.0%-78.8%), specificity was 99.2% (97.8%-99.8%), positive predictive value was 60.0% (31.2%-83.3%), and negative predictive value was 99.0% (97.5%-99.6%). CONCLUSIONS: Our findings suggest that the new research criteria for prodromal PD are a promising tool to identify cases of incident PD over 5 years, arguing for their usefulness in defining target populations for disease-prevention trials. © 2016 International Parkinson and Movement Disorder Society.

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

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

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

17 Review Interventional trials in atypical parkinsonism. 2016

Eschlböck, S / Krismer, F / Wenning, G K. ·Department of Neurology, Medical University of Innsbruck, Anichstraße 35, 6020, Innsbruck, Austria. · Department of Neurology, Medical University of Innsbruck, Anichstraße 35, 6020, Innsbruck, Austria. Electronic address: gregor.wenning@i-med.ac.at. ·Parkinsonism Relat Disord · Pubmed #26421389.

ABSTRACT: Atypical parkinson disorders (APD) are rapidly progressive neurodegenerative diseases with a variable clinical presentation that may even mimic Parkinson's disease. Multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are commonly summarized under this umbrella term. Significant developments in research have expanded knowledge and have broadened available symptomatic treatments, particularly for the treatment of neurogenic orthostatic hypotension. Nonetheless, symptomatic support still remains limited in all of these disorders. Currently, there exists no effective treatment to delay disease progression and disease-modifying trials have failed to provide coherent and convincing results. Recent trials of rasagiline (in MSA), rifampicin (in MSA), tideglusib (in PSP) and davunetide (in PSP) reported negative results. Nevertheless, large cohorts of patients were recruited for interventional studies in the last few years which improved our understanding of trial methodology in APDs immensely. In addition, remarkable progress in basic research has been reported recently and will provide a solid foundation for future therapeutic trials. In this review, we will summarize published randomized, placebo-controlled clinical trials (RCTs) in APDs. Additionally, the design of ongoing and unpublished interventions will be presented.

18 Review Cerebral autoregulation and white matter lesions in Parkinson's disease and multiple system atrophy. 2015

Indelicato, Elisabetta / Fanciulli, Alessandra / Poewe, Werner / Antonini, Angelo / Pontieri, Francesco E / Wenning, Gregor K. ·Department of Neuroscience, Mental Health and Sensory Organs, "Sapienza" University of Rome, Via di Grottarossa 1035, 00189 Rome, Italy; IRCCS Santa Lucia Foundation, Via Ardeatina 306, 00179 Rome, Italy. Electronic address: indelicato.elisabetta@gmail.it. · Department of Neuroscience, Mental Health and Sensory Organs, "Sapienza" University of Rome, Via di Grottarossa 1035, 00189 Rome, Italy; Department of Neurology, Innsbruck Medical University, Anichstraße 35, 6020 Innsbruck, Austria. · Department of Neurology, Innsbruck Medical University, Anichstraße 35, 6020 Innsbruck, Austria. · IRCCS Ospedale San Camillo, Via Alberoni 70, 30126 Venice, Italy. · Department of Neuroscience, Mental Health and Sensory Organs, "Sapienza" University of Rome, Via di Grottarossa 1035, 00189 Rome, Italy; IRCCS Santa Lucia Foundation, Via Ardeatina 306, 00179 Rome, Italy. ·Parkinsonism Relat Disord · Pubmed #26578037.

ABSTRACT: Cerebral autoregulation is a complex homeostatic process which ensures constant brain blood supply, despite continuous blood pressure fluctuations. Recent evidence suggests that in Parkinson's disease (PD) and multiple system atrophy (MSA) this process is maintained in a broadened range of blood pressure values, consistent with an adaptive mechanism to increase tolerance to orthostatic hypotension. In PD and MSA orthostatic hypotension may be accompanied by supine hypertension which has been recently linked with cerebral white matter lesions in these conditions. We hypothesize that cerebral autoregulation adaptation to chronic orthostatic hypotension may be directly related with an increase susceptibility to hypertensive peaks. Evaluation of cerebral autoregulatory behavior may thus represent a novel approach to simultaneously target orthostatic symptoms and silent end-organ damage in alpha-synucleinopathies, with a beneficial impact on cerebrovascular and cognitive outcome.

19 Review The Concept of Prodromal Parkinson's Disease. 2015

Mahlknecht, Philipp / Seppi, Klaus / Poewe, Werner. ·Department of Neurology, Medical University Innsbruck, Austria. · Sobell Department of Motor Neuroscience, UCL Institute of Neurology, London, UK. ·J Parkinsons Dis · Pubmed #26485429.

ABSTRACT: Parkinson's disease (PD) is currently clinically defined by a set of cardinal motor features centred on the presence of bradykinesia and at least one additional motor symptom out of tremor, rigidity or postural instability. However, converging evidence from clinical, neuropathological, and imaging research suggests initiation of PD-specific pathology prior to appearance of these classical motor signs. This latent phase of neurodegeneration in PD is of particular relevance in relation to the development of disease-modifying or neuroprotective therapies which would require intervention at the earliest stages of disease. A key challenge in PD research, therefore, is to identify and validate markers for the preclinical and prodromal stages of the illness. Currently, several nonmotor symptoms have been associated with an increased risk to develop PD in otherwise healthy individuals and ongoing research is aimed at validating a variety of candidate PD biomarkers based on imaging, genetic, proteomic, or metabolomic signatures, supplemented by work on tissue markers accessible to minimally invasive biopsies. In fact, the recently defined MDS research criteria for prodromal PD have included combinations of risk and prodromal markers allowing to define target populations of future disease modification trials.

20 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.

21 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.

22 Review Asian perspectives on the recognition and management of levodopa 'wearing-off' in Parkinson's disease. 2015

Bhidayasiri, Roongroj / Hattori, Nobutaka / Jeon, Beomseok / Chen, Rou-Shayn / Lee, Moon Keen / Bajwa, Jawad A / Mok, Vincent C T / Zhang, Baorong / Syamsudin, Thamrin / Tan, Louis Chew Seng / Jamora, Roland Dominic G / Pisarnpong, Apichart / Poewe, Werner. ·a 1 Chulalongkorn Centre of Excellence for Parkinson's Disease & Related Disorders, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand. · b 2 Juntendo University School of Medicine, Tokyo, Japan. · c 3 Seoul National University, Seoul, South Korea. · d 4 Chang Gung Memorial Hospital, Lingkou, Taiwan. · e 5 Sunway Medical Centre, Jalan Lagoon Selatan, Bandar Sunway, 46150 Petaling Jaya, Selangor, Malaysia. · f 6 National Neuroscience Institute, King Fahad Medical City, Riyadh, Saudi Arabia. · g 7 Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China. · h 8 Department of Neurology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. · i 9 National Brain Centre Hospital, Jakarta, Indonesia. · j 10 National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore. · k 11 Department of Neurosciences, College of Medicine-Philippine General Hospital, University of the Philippines Manila, Manila, Philippines. · l 12 Movement Disorder Service and Section of Neurology, Institute for Neurosciences, St. Luke's Medical Center-Quezon City and Global City, Philippines. · m 13 Department of Neurology, Bangkok Hospital, Bangkok, Thailand. · n 14 Innsbruck Medical University, Innsbruck, Austria. ·Expert Rev Neurother · Pubmed #26390066.

ABSTRACT: Most Parkinson's disease patients will receive levodopa therapy, and of these, the majority will develop some levodopa-induced complications. For many patients, the first complication to develop is the decline in the duration of therapeutic benefit of each levodopa dose, a phenomenon commonly termed 'wearing-off'. There is already extensive literature documenting the epidemiology and management of wearing-off in Parkinson's disease patients of western descent. However, data derived from these studies might not always apply to patients of Asian descent due to genetic variations, differences in co-morbidities or non-availability of certain drugs. This review summarizes the current literature regarding the epidemiology of wearing-off in Asian (including Arab) patients and discusses the management issues in the context of drug availability in Asia.

23 Review Expert Consensus Group report on the use of apomorphine in the treatment of Parkinson's disease--Clinical practice recommendations. 2015

Trenkwalder, Claudia / Chaudhuri, K Ray / García Ruiz, Pedro J / LeWitt, Peter / Katzenschlager, Regina / Sixel-Döring, Friederike / Henriksen, Tove / Sesar, Ángel / Poewe, Werner / Anonymous6190836 / Baker, Mary / Ceballos-Baumann, Andres / Deuschl, Günther / Drapier, Sophie / Ebersbach, Georg / Evans, Andrew / Fernandez, Hubert / Isaacson, Stuart / van Laar, Teus / Lees, Andrew / Lewis, Simon / Martínez Castrillo, Juan Carlos / Martinez-Martin, Pablo / Odin, Per / O'Sullivan, John / Tagaris, Georgios / Wenzel, Karoline. ·Centre of Parkinsonism and Movement Disorders, Paracelsus-Elena Hospital, Kassel, Germany; Department of Neurosurgery, University Medical Centre, Goettingen, Germany. Electronic address: trenkwalder@pk-mx.de. · National Parkinson Foundation Centre of Excellence, Kings College Hospital, Denmark Hill Campus, London, UK. · Movement Disorders Unit, Department of Neurology, Fundacion Jimenez Diaz, Madrid, Spain. · Wayne State University School of Medicine, Parkinson's Disease and Movement Disorders Program, Henry Ford West Bloomfield Hospital, West Bloomfield, MI, USA. · Department of Neurology and Karl Landsteiner Institute for Neuroimmunological and Neurodegenerative Disorders, Danube Hospital, Vienna, Austria. · Centre of Parkinsonism and Movement Disorders, Paracelsus-Elena Hospital, Kassel, Germany; Department of Neurology, Philipps-University, Marburg, Germany. · Movement Disorder Clinic, Bispebjerg Hospital, Copenhagen, Denmark. · Department of Neurology, Hospital Clínico Universitario, Santiago de Compostela, Spain. · Department of Neurology, Medical University of Innsbruck, Austria. ·Parkinsonism Relat Disord · Pubmed #26189414.

ABSTRACT: Extensive published evidence supports the use of subcutaneously-administered apomorphine as an effective therapy for Parkinson's disease (PD) but to date no consensus recommendations have been available to guide healthcare professionals in the optimal application of apomorphine therapy in clinical practice. This document outlines best-practice recommendations for selecting appropriate candidates for apomorphine intermittent injection (the pen-injection formulation) or apomorphine continuous infusion (the pump formulation), for initiating patients onto therapy and for managing their ongoing treatment. Apomorphine is a suitable therapeutic option for PD patients who experience troublesome 'off' periods despite optimized treatment with oral PD medications. Due to its speed of onset, apomorphine injection is particularly suited to those patients requiring rapid, reliable relief of both unpredictable and predictable 'off' periods, those who require reliable and fast relief when anticipating an 'off', those with levodopa absorption or gastric emptying problems resulting in delayed or failed 'on', or for rapid relief of early morning dystonia or akinesia. Apomorphine infusion(1) is suited for patients whose 'off' periods can no longer be adequately controlled by standard oral PD treatment or for those in whom rescue doses of apomorphine injection are effective but either needed too frequently (more than 4-6 times per day), or are associated with increasing dyskinesia. In addition to treating motor fluctuations, there is evidence that apomorphine infusion may be effective for the management of specific non-motor symptoms of PD associated with 'off' periods. Apomorphine infusion is less invasive than other non-oral treatment options for advancing disease, intrajejunal levodopa infusion and deep-brain stimulation.

24 Review Novel formulations and modes of delivery of levodopa. 2015

Poewe, Werner / Antonini, Angelo. ·Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. ·Mov Disord · Pubmed #25476691.

ABSTRACT: Ever since its early clinical use in the 1960s, levodopa has remained the gold standard of symptomatic efficacy in the drug treatment of Parkinson's disease (PD). Motor response fluctuations and drug-induced dyskinesias seriously compromise the unparalleled symptomatic efficacy of l-dopa during long-term treatment. Discontinuous drug delivery resulting from the short half-life of l-dopa and erratic gastrointestinal absorption plays a major role in the pathophysiology of these motor complications. Several approaches to improve the pharmacokinetics and ways of administration of l-dopa are in different stages of clinical development and include novel formulations as well as nonoral routes of drug delivery. IPX066 is a novel extended-release l-dopa capsule that has successfully completed phase III clinical trials while the l-dopa prodrug XP21279 and a gastric retention formulation ("accordion pill") are in earlier phases of clinical development. Novel enzyme inhibitors enhancing l-dopa efficacy and half-life are also still being developed, including a novel catechol-O-methyltransferase inhibitor with once-daily pharmacokinetics, and there are studies testing the effects of increasing the dose of amino acid decarboxylase inhibitors given concomitantly with l-dopa. Intrajejunal infusion of a gel formulation of l-dopa/carbidopa is in clinical use in Europe, and its efficacy to smooth out motor fluctuations has recently been shown in a randomized, controlled trial. Subcutaneous and intrapulmonal delivery routes of l-dopa have reached phase III of clinical development. After more than 50 years of clinical use, l-dopa not only remains the gold standard of symptomatic efficacy, but it also remains a drug in active clinical development.

25 Review Multiple system atrophy as emerging template for accelerated drug discovery in α-synucleinopathies. 2014

Krismer, Florian / Jellinger, Kurt A / Scholz, Sonja W / Seppi, Klaus / Stefanova, Nadia / Antonini, Angelo / Poewe, Werner / Wenning, Gregor K. ·Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. Electronic address: florian.krismer@i-med.ac.at. · Institute of Clinical Neurobiology, Vienna, Austria. Electronic address: kurt.jellinger@univie.ac.at. · Department of Neurology, The Johns Hopkins Hospital, Baltimore, MD 21287, USA. Electronic address: sonja.w.scholz@googlemail.com. · Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. Electronic address: klaus.seppi@uki.at. · Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. Electronic address: nadia.stefanova@i-med.ac.at. · Department of Parkinson's Disease and Movement Disorders, IRCCS San Camillo, Venice, Italy. Electronic address: angelo3000@yahoo.com. · Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. Electronic address: werner.poewe@i-med.ac.at. · Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. Electronic address: Gregor.Wenning@i-med.ac.at. ·Parkinsonism Relat Disord · Pubmed #24894118.

ABSTRACT: There is evidence that the α-synucleinopathies Parkinson's disease (PD) and the Parkinson variant of multiple system atrophy (MSA-P) overlap at multiple levels. Both disorders are characterized by deposition of abnormally phosphorylated fibrillar α-synuclein within the central nervous system suggesting shared pathophysiological mechanisms. Despite the considerable clinical overlap in the early disease stages, MSA-P, in contrast to PD, is fatal and rapidly progressive. Moreover recent clinical studies have shown that surrogate markers of disease progression can be quantified easily and may reliably depict the rapid course of MSA. We therefore posit that, MSA-P may be exploited as a filter barrier in the development of disease-modifying therapeutic strategies targeting common pathophysiological mechanisms of α-synucleinopathies. This approach might reduce the number of negative phase III clinical trials, and, in turn, shift the available resources to earlier development stages, thereby increasing the number of candidate compounds validated.

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