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Parkinson Disease: HELP
Articles from San Francisco
Based on 234 articles published since 2008
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These are the 234 published articles about Parkinson Disease that originated from San Francisco during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8 · 9 · 10
1 Editorial Mendel and urate: Acid test or random noise? 2018

Brown, Ethan G / Goldman, Samuel M / Tanner, Caroline M. ·Department of Neurology, University of California - San Francisco, San Francisco, CA, USA; Department of Neurology, Weil Institute for Neurosciences, University of California - San Francisco, San Francisco, CA, USA. · Department of Neurology, University of California - San Francisco, San Francisco, CA, USA; Division of Occupational and Environmental Medicine, University of California - San Francisco, San Francisco, CA, USA; Medical Service, San Francisco Veterans Affairs Health Care System, San Francisco, CA, USA. · Department of Neurology, University of California - San Francisco, San Francisco, CA, USA; Department of Neurology, Weil Institute for Neurosciences, University of California - San Francisco, San Francisco, CA, USA; Parkinson's Disease Research, Education and Clinical Center, San Francisco Veterans Affairs Health Care System, San Francisco, CA, USA. Electronic address: Caroline.tanner@ucsf.edu. ·Parkinsonism Relat Disord · Pubmed #30100365.

ABSTRACT: -- No abstract --

2 Editorial Role of Neuroinflammation in Parkinson Disease: The Enigma Continues. 2016

Mehta, Shyamal H / Tanner, Caroline M. ·Department of Neurology, Mayo Clinic, Scottsdale, AZ. Electronic address: mehta.shyamal@mayo.edu. · San Francisco Veterans Affairs Medical Center and Department of Neurology, University of California, San Francisco, CA. ·Mayo Clin Proc · Pubmed #27712631.

ABSTRACT: -- No abstract --

3 Editorial More than just a movement disorder: Why cognitive training is needed in Parkinson disease. 2015

Ventura, Maria I / Edwards, Jerri D / Barnes, Deborah E. ·From the Departments of Geriatrics (M.I.V.) and Psychiatry and Epidemiology & Statistics (D.E.B.), University of California, San Francisco · the School of Aging Studies (J.D.E.), University of South Florida, Tampa · and the San Francisco VA Medical Center (D.E.B.), San Francisco, CA. ·Neurology · Pubmed #26519546.

ABSTRACT: -- No abstract --

4 Editorial Commentary on "Adaptive deep brain stimulation in advanced Parkinson disease". 2013

Starr, Philip A / Ostrem, Jill L. ·Department of Neurosurgery, University of California, San Francisco, San Francisco, CA. ·Ann Neurol · Pubmed #23818322.

ABSTRACT: -- No abstract --

5 Review Flavonoids as Therapeutic Agents in Alzheimer's and Parkinson's Diseases: A Systematic Review of Preclinical Evidences. 2018

de Andrade Teles, Roxana Braga / Diniz, Tâmara Coimbra / Costa Pinto, Tiago Coimbra / de Oliveira Júnior, Raimundo Gonçalves / Gama E Silva, Mariana / de Lavor, Érica Martins / Fernandes, Antonio Wilton Cavalcante / de Oliveira, Ana Paula / de Almeida Ribeiro, Fernanda Pires Rodrigues / da Silva, Amanda Alves Marcelino / Cavalcante, Taisy Cinthia Ferro / Quintans Júnior, Lucindo José / da Silva Almeida, Jackson Roberto Guedes. ·Postgraduate Program in Biotechnology, State University of Feira de Santana, 44036-900 Feira de Santana, BA, Brazil. · Federal University of San Francisco Valley, 56304-205 Petrolina, PE, Brazil. · Postgraduate Program in Neuropsychiatry and Behavioural Sciences, Federal University of Pernambuco, 50740-521 Recife, PE, Brazil. · UMRi CNRS 7266 LIENSs University of La Rochelle, La Rochelle, France. · University of Pernambuco, 56328-903 Petrolina, PE, Brazil. · Department of Physiology, Federal University of Sergipe, 49100-000 São Cristóvão, SE, Brazil. ·Oxid Med Cell Longev · Pubmed #29861833.

ABSTRACT: Alzheimer's and Parkinson's diseases are considered the most common neurodegenerative disorders, representing a major focus of neuroscience research to understanding the cellular alterations and pathophysiological mechanisms involved. Several natural products, including flavonoids, are considered able to cross the blood-brain barrier and are known for their central nervous system-related activity. Therefore, studies are being conducted with these chemical constituents to analyze their activities in slowing down the progression of neurodegenerative diseases. The present systematic review summarizes the pharmacological effects of flavonoids in animal models for Alzheimer's and Parkinson's diseases. A PRISMA model for systematic review was utilized for this search. The research was conducted in the following databases: PubMed, Web of Science, BIREME, and Science Direct. Based on the inclusion criteria, 31 articles were selected and discussed in this review. The studies listed revealed that the main targets of action for Alzheimer's disease therapy were reduction of reactive oxygen species and amyloid beta-protein production, while for Parkinson's disease reduction of the cellular oxidative potential and the activation of mechanisms of neuronal death. Results showed that a variety of flavonoids is being studied and can be promising for the development of new drugs to treat neurodegenerative diseases. Moreover, it was possible to verify that there is a lack of translational research and clinical evidence of these promising compounds.

6 Review iPS cells in the study of PD molecular pathogenesis. 2018

Cobb, Melanie M / Ravisankar, Abinaya / Skibinski, Gaia / Finkbeiner, Steven. ·Gladstone Institutes, the Taube/Koret Center for Neurodegenerative Disease, San Francisco, CA, 94158, USA. · Gladstone Institutes, the Taube/Koret Center for Neurodegenerative Disease, San Francisco, CA, 94158, USA. steve.finkbeiner@gladstone.ucsf.edu. · Department of Neurology, University of California, San Francisco, CA, 94143, USA. steve.finkbeiner@gladstone.ucsf.edu. · Department Physiology, University of California, San Francisco, CA, 94143, USA. steve.finkbeiner@gladstone.ucsf.edu. · Graduate Programs in Neuroscience and Biomedical Sciences, University of California, San Francisco, CA, 94143, USA. steve.finkbeiner@gladstone.ucsf.edu. ·Cell Tissue Res · Pubmed #29234887.

ABSTRACT: Parkinson's disease (PD) is the second most common neurodegenerative disease and its pathogenic mechanisms are poorly understood. The majority of PD cases are sporadic but a number of genes are associated with familial PD. Sporadic and familial PD have many molecular and cellular features in common, suggesting some shared pathogenic mechanisms. Induced pluripotent stem cells (iPSCs) have been derived from patients harboring a range of different mutations of PD-associated genes. PD patient-derived iPSCs have been differentiated into relevant cell types, in particular dopaminergic neurons and used as a model to study PD. In this review, we describe how iPSCs have been used to improve our understanding of the pathogenesis of PD. We describe what cellular and molecular phenotypes have been observed in neurons derived from iPSCs harboring known PD-associated mutations and what common pathways may be involved.

7 Review Pedunculopontine nucleus deep brain stimulation in Parkinson's disease: A clinical review. 2018

Thevathasan, Wesley / Debu, Bettina / Aziz, Tipu / Bloem, Bastiaan R / Blahak, Christian / Butson, Christopher / Czernecki, Virginie / Foltynie, Thomas / Fraix, Valerie / Grabli, David / Joint, Carole / Lozano, Andres M / Okun, Michael S / Ostrem, Jill / Pavese, Nicola / Schrader, Christoph / Tai, Chun-Hwei / Krauss, Joachim K / Moro, Elena / Anonymous621156. ·Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Australia and the Bionics Institute of Australia, Melbourne, Australia. · Movement Disorders Center, Division of Neurology, Centre Hospitalier Universitaire (CHU) Grenoble, Grenoble Alpes University, Grenoble, France. · Department of Neurosurgery, John Radcliffe Hospital, University of Oxford, Oxford, UK. · Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands. · Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Heidelberg, Germany. · Department of Bioengineering, Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, USA. · Department of Neurology, Institut de Cerveau et de la Moelle épinière, Sorbonne Universités, University Pierre-and-Marie-Curie (UPMC) Université, Paris, France. · Sobell Department of Motor Neuroscience, University College London (UCL) Institute of Neurology, United Kingdom. · Department of Neurology, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtière University Hospital, Paris, France. · Department of Neurosurgery, Toronto Western Hospital, University of Toronto, Toronto, Canada. · Departments of Neurology and Neurosurgery, University of Florida Center for Movement Disorders, Gainesville, Florida, USA. · Department of Neurology, UCSF Movement Disorder and Neuromodulation Center, University of California, San Francisco, USA. · Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK. · Department of Clinical Medicine, Centre for Functionally Integrative Neuroscience, University of Aarhus, Aarhus, Denmark. · Department of Neurology, Hannover Medical School, Hannover, Germany. · Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan. · Department of Neurosurgery, Hannover Medical School, Hannover, Germany. ·Mov Disord · Pubmed #28960543.

ABSTRACT: Pedunculopontine nucleus region deep brain stimulation (DBS) is a promising but experimental therapy for axial motor deficits in Parkinson's disease (PD), particularly gait freezing and falls. Here, we summarise the clinical application and outcomes reported during the past 10 years. The published dataset is limited, comprising fewer than 100 cases. Furthermore, there is great variability in clinical methodology between and within surgical centers. The most common indication has been severe medication refractory gait freezing (often associated with postural instability). Some patients received lone pedunculopontine nucleus DBS (unilateral or bilateral) and some received costimulation of the subthalamic nucleus or internal pallidum. Both rostral and caudal pedunculopontine nucleus subregions have been targeted. However, the spread of stimulation and variance in targeting means that neighboring brain stem regions may be implicated in any response. Low stimulation frequencies are typically employed (20-80 Hertz). The fluctuating nature of gait freezing can confound programming and outcome assessments. Although firm conclusions cannot be drawn on therapeutic efficacy, the literature suggests that medication refractory gait freezing and falls can improve. The impact on postural instability is unclear. Most groups report a lack of benefit on gait or limb akinesia or dopaminergic medication requirements. The key question is whether pedunculopontine nucleus DBS can improve quality of life in PD. So far, the evidence supporting such an effect is minimal. Development of pedunculopontine nucleus DBS to become a reliable, established therapy would likely require a collaborative effort between experienced centres to clarify biomarkers predictive of response and the optimal clinical methodology. © 2017 International Parkinson and Movement Disorder Society.

8 Review Genetics of Synucleinopathies. 2018

Nussbaum, Robert L. ·Volunteer Clinical Faculty, UCSF School of Medicine, University of California, San Francisco, San Francisco, California 94143. ·Cold Spring Harb Perspect Med · Pubmed #28213435.

ABSTRACT: Parkinson's disease (PD), diffuse Lewy body disease (DLBD), and multiple system atrophy (MSA) constitute the three major neurodegenerative disorders referred to as synucleinopathies because both genetic and pathological results implicate the α-synuclein protein in their pathogenesis. PD and DLBD are recognized as closely related diseases with substantial clinical and pathological overlap. MSA, on the other hand, has a distinctive clinical presentation and neuropathological profile. In this review, we will summarize the evidence linking α-synuclein to these three disorders. Hundreds of patients with point or copy number mutations in the gene encoding α-synuclein,

9 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.

10 Review Neurodegenerative signaling factors and mechanisms in Parkinson's pathology. 2017

Goswami, Poonam / Joshi, Neeraj / Singh, Sarika. ·Neuronal Cell Death Mechanisms Laboratory, Toxicology Division, CSIR-Central Drug Research Institute, Lucknow, 226031, Uttar Pradesh, India. · Department of Biochemistry and Biophysics, Helen Diller Comprehensive Cancer Center, University of California San Francisco, USA. · Neuronal Cell Death Mechanisms Laboratory, Toxicology Division, CSIR-Central Drug Research Institute, Lucknow, 226031, Uttar Pradesh, India. Electronic address: sarika_singh@cdri.res.in. ·Toxicol In Vitro · Pubmed #28627426.

ABSTRACT: Parkinson's disease (PD) is a chronic and progressive degenerative disorder of central nervous system which is mainly characterized by selective loss of dopaminergic neurons in the nigrostrial pathway. Clinical symptoms of this devastating disease comprise motor impairments such as resting tremor, bradykinesia, postural instability and rigidity. Current medications only provide symptomatic relief but fail to halt the dopaminergic neuronal death. While the etiology of dopaminergic neuronal death is not fully understood, combination of various molecular mechanisms seems to play a critical role. Studies from experimental animal models have provided crucial insights into the molecular mechanisms in disease pathogenesis and recognized possible targets for therapeutic interventions. Recent findings implicate the involvement of abnormal protein accumulation and phosphorylation, mitochondrial dysfunction, oxidative damage and deregulated kinase signaling as key molecular mechanisms affecting the normal function as well survival of dopaminergic neurons. Here we discuss the relevant findings on the PD pathology related mechanisms and recognition of the cell survival mechanisms which could be used as targets for neuroprotective strategies in preventing this devastating disorder.

11 Review The vicious circle of hypometabolism in neurodegenerative diseases: Ways and mechanisms of metabolic correction. 2017

Zilberter, Yuri / Zilberter, Misha. ·Aix-Marseille Université, INSERM UMR1106, Institut de Neurosciences des Systèmes, Marseille, France. · Gladstone Institute of Neurological Disease, 1650 Owens Street, San Francisco, California, 94158, USA. ·J Neurosci Res · Pubmed #28463438.

ABSTRACT: Hypometabolism, characterized by decreased brain glucose consumption, is a common feature of many neurodegenerative diseases. Initial hypometabolic brain state, created by characteristic risk factors, may predispose the brain to acquired epilepsy and sporadic Alzheimer's and Parkinson's diseases, which are the focus of this review. Analysis of available data suggests that deficient glucose metabolism is likely a primary initiating factor for these diseases, and that resulting neuronal dysfunction further promotes the metabolic imbalance, establishing an effective positive feedback loop and a downward spiral of disease progression. Therefore, metabolic correction leading to the normalization of abnormalities in glucose metabolism may be an efficient tool to treat the neurological disorders by counteracting their primary pathological mechanisms. Published and preliminary experimental results on this approach for treating Alzheimer's disease and epilepsy models support the efficacy of metabolic correction, confirming the highly promising nature of the strategy. © 2017 Wiley Periodicals, Inc.

12 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.

13 Review Biomarker-driven phenotyping in Parkinson's disease: A translational missing link in disease-modifying clinical trials. 2017

Espay, Alberto J / Schwarzschild, Michael A / Tanner, Caroline M / Fernandez, Hubert H / Simon, David K / Leverenz, James B / Merola, Aristide / Chen-Plotkin, Alice / Brundin, Patrik / Kauffman, Marcelo A / Erro, Roberto / Kieburtz, Karl / Woo, Daniel / Macklin, Eric A / Standaert, David G / Lang, Anthony E. ·Department of Neurology, UC Gardner Neuroscience Institute, Gardner Center for Parkinson's disease and Movement Disorders, University of Cincinnati, Cincinnati, Ohio, USA. · MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA. · Department of Neurology, University of California-San Francisco and the Parkinson's Disease Research Education and Clinical Center, San Francisco Veterans Affairs Medical Center, San Francisco, California, USA. · Center for Neurological Restoration, Cleveland Clinic, Cleveland, Ohio, USA. · Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA. · Lou Ruvo Center for Brain Health, Neurological Institute, Cleveland Clinic, Cleveland, Ohio, USA. · Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, Michigan, USA. · Consultorio y Laboratorio de Neurogenética, Centro Universitario de Neurología "José María Ramos Mejía" y División Neurología, Hospital JM Ramos Mejía, Facultad de Medicina, UBA, and Programa de Medicina de Precision y Genomica Clinica, Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomédicas, Universidad Austral-CONICET, Pilar, Argentina. · Sobell department of Motor Neuroscience and Movement Disorders, University College London, Institute of Neurology, London, United Kingdom. · Department of Neuroscience, Biomedicine and Movement Science, University of Verona, Verona, Italy. · Department of Neurology and CHET, University of Rochester Medical Center, Rochester, New York, USA. · Department of Neurology and Rehabilitation Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio, USA. · Department of Medicine, Biostatistics Center, Massachusetts General Hospital, Boston, Massachusetts, USA. · Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA. · Morton and Gloria Shulman Movement Disorders Center, Toronto Western Hospital and The Edmond J. Safra Program in PD, Toronto, Ontario, Canada, University of Toronto, Toronto, Ontario, Canada. ·Mov Disord · Pubmed #28233927.

ABSTRACT: Past clinical trials of putative neuroprotective therapies have targeted PD as a single pathogenic disease entity. From an Oslerian clinicopathological perspective, the wide complexity of PD converges into Lewy bodies and justifies a reductionist approach to PD: A single-mechanism therapy can affect most of those sharing the classic pathological hallmark. From a systems-biology perspective, PD is a group of disorders that, while related by sharing the feature of nigral dopamine-neuron degeneration, exhibit unique genetic, biological, and molecular abnormalities, which probably respond differentially to a given therapeutic approach, particularly for strategies aimed at neuroprotection. Under this model, only biomarker-defined, homogenous subtypes of PD are likely to respond optimally to therapies proven to affect the biological processes within each subtype. Therefore, we suggest that precision medicine applied to PD requires a reevaluation of the biomarker-discovery effort. This effort is currently centered on correlating biological measures to clinical features of PD and on identifying factors that predict whether various prodromal states will convert into the classical movement disorder. We suggest, instead, that subtyping of PD requires the reverse view, where abnormal biological signals (i.e., biomarkers), rather than clinical definitions, are used to define disease phenotypes. Successful development of disease-modifying strategies will depend on how relevant the specific biological processes addressed by an intervention are to the pathogenetic mechanisms in the subgroup of targeted patients. This precision-medicine approach will likely yield smaller, but well-defined, subsets of PD amenable to successful neuroprotection. © 2017 International Parkinson and Movement Disorder Society.

14 Review Palliative care and Parkinson's disease: Meeting summary and recommendations for clinical research. 2017

Kluger, Benzi M / Fox, Siobhán / Timmons, Suzanne / Katz, Maya / Galifianakis, Nicholas B / Subramanian, Indu / Carter, Julie H / Johnson, Miriam J / Richfield, Edward W / Bekelman, David / Kutner, Jean S / Miyasaki, Janis. ·Department of Neurology, University of Colorado School of Medicine, Anschutz Medical Campus, 12631 E 17th Ave, Mail Stop B185, Aurora, CO 80045, USA. Electronic address: benzi.kluger@ucdenver.edu. · Centre for Gerontology and Rehabilitation, School of Medicine, University College Cork, The Bungalow, Block 13, St. Finbarr's Hospital, Douglas Road, Cork, Republic of Ireland. · Department of Neurology, University of California San Francisco, 4150 Clement St. #219G, San Francisco, CA 94143, USA. · Department of Neurology, University of California Los Angeles, 300 UCLA Medical Plaza, Suite B200, Los Angeles, CA 90095, USA. · Department of Neurology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, L226, Portland, OR 97239, USA. · Hull York Medical School, University of Hull, Hertford Building, Hull HU6 7RX, UK. · Department of Elderly Medicine, Leeds Teaching Hospitals Trust, UK. · Department of Internal Medicine, University of Colorado School of Medicine, Anschutz Medical Campus, 12401 East 17th Avenue, Mail Stop B180, Aurora, CO 80045, USA; Department of Medicine, VA Eastern Colorado Health Care System, 1055 Clermont Street, Denver, CO 80220, USA. · Department of Internal Medicine, University of Colorado School of Medicine, Anschutz Medical Campus, 12401 East 17th Avenue, Mail Stop B180, Aurora, CO 80045, USA. · Division of Neurology, University of Alberta, 13-103 Clinical Sciences Building, 11350-83 Avenue, Edmonton, Alberta T6G 2R3, Canada. ·Parkinsonism Relat Disord · Pubmed #28108265.

ABSTRACT: INTRODUCTION: Palliative care is an approach to caring for patients and families affected by serious illnesses that focuses on the relief of suffering through the management of medical symptoms, psychosocial issues, advance care planning and spiritual wellbeing. Over the past decade there has been an emerging clinical and research interest in the application of palliative care approaches to Parkinson's disease (PD) and outpatient palliative care services are now offered by several movement disorders centers. METHODS: An International Working Group Meeting on PD and Palliative Care supported by the Parkinson's Disease Foundation was held in October 2015 to review the current state of the evidence and to make recommendations for clinical research and practice. RESULTS: Topics included: 1) Defining palliative care for PD; 2) Lessons from palliative care for heart failure and other chronic illnesses; 3) Patient and caregiver Needs; 4) Needs assessment tools; 5) Intervention strategies; 6) Predicting prognosis and hospice referrals; 7) Choice of appropriate outcome measures; 8) Implementation, dissemination and education research; and 9) Need for research collaborations. We provide an overview of these discussions, summarize current evidence and practices, highlight gaps in our knowledge and make recommendations for future research. CONCLUSIONS: Palliative Care for PD is a rapidly growing area which holds great promise for improving outcomes for PD patients and their caregivers. While clinical research in this area can build from lessons learned in other diseases, there is a need for observational, methodological and interventional research to address the unique needs of PD patients and caregivers.

15 Review The Search for a Peripheral Biopsy Indicator of α-Synuclein Pathology for Parkinson Disease. 2017

Lee, John M / Derkinderen, Pascal / Kordower, Jeffrey H / Freeman, Roy / Munoz, David G / Kremer, Thomas / Zago, Wagner / Hutten, Samantha J / Adler, Charles H / Serrano, Geidy E / Beach, Thomas G. ·Department of Pathology, NorthShore University Health System, University of Chicago, Pritzker School of Medicine, Evanston, Illinois, USA. · Inserm, U913, Nantes F-44035; Nantes University, Nantes F-44035; Department of Neurology, CHU Nantes, Nantes F-44093, France. · Center for Brain Repair, Department of Pathology, Rush Medical College, Chicago, Illinois, USA. · Harvard Medical School; Center for Autonomic and Peripheral Nerve Disorders, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA. · Laboratory Medicine and Keenan Research Centre for Biomedical Research of the Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. · Roche Pharmaceutical Research and Early Development, Nord DTA, Biomarker and Clinical Imaging, Roche Innovation Center, F Hoffman-La Roche, Ltd., Basel, Switzerland. · Prothena Biosciences, Inc., South San Francisco, California · Prothena Biosciences, Inc., South San Francisco, California (WZ); Michael J. Fox Foundation for Parkinson's Research, New York, New York, USA. · Department of Neurology, Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale, Arizona, USA. · Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, Arizona, USA. ·J Neuropathol Exp Neurol · Pubmed #28069931.

ABSTRACT: The neuropathological hallmark of Parkinson disease (PD) is abnormal accumulation of α-synuclein (α-syn). Demonstrating pathological α-syn in live patients would be useful for identifying and monitoring PD patients. To date, however, imaging and biofluid approaches have not permitted premortem assessment of pathological α-syn. α-syn pathology in the peripheral nervous system of patients with PD has been demonstrated in studies dating back more than 40 years. More recent work suggests that colon, submandibular gland and skin biopsies could be useful as expedient biomarkers but histological differentiation of pathological and normal peripheral α-syn has been challenging and multiple research groups have reported variable results. A variety of immunohistochemical methods have been employed but almost all studies to date originated at single centers with no independent, blinded replication. To address these issues, the Michael J. Fox Foundation for Parkinson's Research sponsored a series of meetings and investigations by several research groups with relevant experience. The major finding reported herein was that biopsies can be used to distinguish PD patients from normal subjects. However, full assessment of the clinical potential of biopsy will only be achieved through large, multicenter trials in which both the initial detection methodology and histology have been assessed by blinded panels of pathologists.

16 Review Machine learning for large-scale wearable sensor data in Parkinson's disease: Concepts, promises, pitfalls, and futures. 2016

Kubota, Ken J / Chen, Jason A / Little, Max A. ·Department of Data Science, tranSMART Foundation, Wakefield, Massachusetts, USA. Ken.Kubota@transmartfoundation.org. · Verge Genomics, San Francisco, California, USA. · Interdepartmental Program in Bioinformatics, University of California at Los Angeles, Los Angeles, California, USA. · Aston University, Aston Triangle, Birmingham, United Kingdom. · Media Lab, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. ·Mov Disord · Pubmed #27501026.

ABSTRACT: For the treatment and monitoring of Parkinson's disease (PD) to be scientific, a key requirement is that measurement of disease stages and severity is quantitative, reliable, and repeatable. The last 50 years in PD research have been dominated by qualitative, subjective ratings obtained by human interpretation of the presentation of disease signs and symptoms at clinical visits. More recently, "wearable," sensor-based, quantitative, objective, and easy-to-use systems for quantifying PD signs for large numbers of participants over extended durations have been developed. This technology has the potential to significantly improve both clinical diagnosis and management in PD and the conduct of clinical studies. However, the large-scale, high-dimensional character of the data captured by these wearable sensors requires sophisticated signal processing and machine-learning algorithms to transform it into scientifically and clinically meaningful information. Such algorithms that "learn" from data have shown remarkable success in making accurate predictions for complex problems in which human skill has been required to date, but they are challenging to evaluate and apply without a basic understanding of the underlying logic on which they are based. This article contains a nontechnical tutorial review of relevant machine-learning algorithms, also describing their limitations and how these can be overcome. It discusses implications of this technology and a practical road map for realizing the full potential of this technology in PD research and practice. © 2016 International Parkinson and Movement Disorder Society.

17 Review The best medicine? The influence of physical activity and inactivity on Parkinson's disease. 2016

LaHue, Sara C / Comella, Cynthia L / Tanner, Caroline M. ·Kaiser Permanente San Francisco Medical Center, San Francisco, California, USA. · Rush Medical Center, Neurological Sciences, Chicago, Illinois, USA. · San Francisco Veterans Affairs Medical Center and Department of Neurology, University of California, San Francisco, California, USA. caroline.tanner@ucsf.edu. ·Mov Disord · Pubmed #27477046.

ABSTRACT: The incidence of Parkinson's disease (PD) is expected to increase as our population ages and will likely strain the projected capacity of our health care system. Despite being the most common movement disorder, there have been few noninvasive therapeutic advances for people with PD since the first levodopa clinical trial in 1961. The study of PD pathogenesis, combined with an appreciation for the biochemical mechanisms by which physical activity and exercise may impact physiology, has resulted in emerging hypotheses for new modifiable risk factors for PD. Physical activity and exercise as a means of preventing PD, or maintaining the functionality of people with PD, are a promising area of investigation. Conversely, physical inactivity is implicated in many disease states, some of which are also correlated with the development of PD, such as metabolic syndrome. The primary relationship between these diseases is likely rooted in heightened inflammation and oxidative stress at the cellular level. Physical activity and exercise as a means of attenuating inflammation have led to increased interest in related potential therapeutic targets for PD. Ultimately, these findings may translate into low-cost, universally available therapies for PD disease modification or prevention. © 2016 International Parkinson and Movement Disorder Society.

18 Review Design and Synthesis of Dopaminergic Agonists. 2016

Matute, Maria Soledad / Matute, Rosa / Merino, Pedro. ·Department of Synthesis and Structure of Biomolecules, Faculty of Sciences, University of Zaragoza, Campus San Francisco, 50009 Zaragoza, Spain. pmerino@unizar.es. ·Curr Med Chem · Pubmed #27142290.

ABSTRACT: The use of dopaminergic agonists is key in the treatment of Parkinson's disease and related central nervous system (CNS) neurodegenerative disorders. Despite there are a number of commercialized dopaminergic agonists that are currently being used successfully in the first stages of the disease, they often fail to provide sustained clinical benefit for a long period due to the appearance of side-effects such as augmentation, sleepiness, nausea, hypothension, and compulsive behaviors among others. New dopaminergic agonists with less side effects are being developed. These novel compounds offer an alternative when the disease progresses and patients fail to respond to standard dopaminergic treatments or side-effects increased. Chemistry, and in particular chemical synthesis, has played a major role in bringing synthetic dopaminergic agonists to the clinic and continues to be crucial for the development of new and necessary drugs for long-term treatments with less undesired side effects. A number of structural modifications of parent compounds have led to enhanced agonism but also partial agonism or even antagonism of one or more dopamine receptors. In some cases, these activities are accompanied by agonist effect at serotonin receptors which suggests a potential clinical application in the treatment of schizophrenia In this review, chemical synthesis of dopaminergic agents, their affinity, and the corresponding agonist/antagonist effects will be highlighted.

19 Review Remote Physical Activity Monitoring in Neurological Disease: A Systematic Review. 2016

Block, Valerie A J / Pitsch, Erica / Tahir, Peggy / Cree, Bruce A C / Allen, Diane D / Gelfand, Jeffrey M. ·Graduate Program in Physical Therapy, University of California San Francisco/ San Francisco State University, San Francisco, California, United States of America. · Department of Physical Therapy and Rehabilitation Science, University of California San Francisco, San Francisco, California, United States of America. · University of California San Francisco Library, San Francisco, California, United States of America. · Multiple Sclerosis and Neuroinflammation Center, Department of Neurology, University of California San Francisco, San Francisco, California, United States of America. ·PLoS One · Pubmed #27124611.

ABSTRACT: OBJECTIVE: To perform a systematic review of studies using remote physical activity monitoring in neurological diseases, highlighting advances and determining gaps. METHODS: Studies were systematically identified in PubMed/MEDLINE, CINAHL and SCOPUS from January 2004 to December 2014 that monitored physical activity for ≥24 hours in adults with neurological diseases. Studies that measured only involuntary motor activity (tremor, seizures), energy expenditure or sleep were excluded. Feasibility, findings, and protocols were examined. RESULTS: 137 studies met inclusion criteria in multiple sclerosis (MS) (61 studies); stroke (41); Parkinson's Disease (PD) (20); dementia (11); traumatic brain injury (2) and ataxia (1). Physical activity levels measured by remote monitoring are consistently low in people with MS, stroke and dementia, and patterns of physical activity are altered in PD. In MS, decreased ambulatory activity assessed via remote monitoring is associated with greater disability and lower quality of life. In stroke, remote measures of upper limb function and ambulation are associated with functional recovery following rehabilitation and goal-directed interventions. In PD, remote monitoring may help to predict falls. In dementia, remote physical activity measures correlate with disease severity and can detect wandering. CONCLUSIONS: These studies show that remote physical activity monitoring is feasible in neurological diseases, including in people with moderate to severe neurological disability. Remote monitoring can be a psychometrically sound and responsive way to assess physical activity in neurological disease. Further research is needed to ensure these tools provide meaningful information in the context of specific neurological disorders and patterns of neurological disability.

20 Review Mechanisms of mitophagy: PINK1, Parkin, USP30 and beyond. 2016

Bingol, Baris / Sheng, Morgan. ·Department of Neuroscience, Genentech Inc, South San Francisco, CA 94080, USA. Electronic address: bingol.baris@gene.com. · Department of Neuroscience, Genentech Inc, South San Francisco, CA 94080, USA. ·Free Radic Biol Med · Pubmed #27094585.

ABSTRACT: Mitochondrial quality control is central for maintaining a healthy population of mitochondria. Two Parkinson's disease genes, mitochondrial kinase PINK1 and ubiquitin ligase Parkin, degrade damaged mitochondria though mitophagy. In this pathway, PINK1 senses mitochondrial damage and activates Parkin by phosphorylating Parkin and ubiquitin. Activated Parkin then builds ubiquitin chains on damaged mitochondria to tag them for degradation in lysosomes. USP30 deubiquitinase acts as a brake on mitophagy by opposing Parkin-mediated ubiquitination. Human genetic data point to a role for mitophagy defects in neurodegenerative diseases. This review highlights the molecular mechanisms of the mitophagy pathway and the recent advances in the understanding of mitophagy in vivo.

21 Review AAV viral vector delivery to the brain by shape-conforming MR-guided infusions. 2016

Bankiewicz, Krystof S / Sudhakar, Vivek / Samaranch, Lluis / San Sebastian, Waldy / Bringas, John / Forsayeth, John. ·Interventional Neuro Center, Department of Neurological Surgery, University of California San Francisco, San Francisco, CA 94110, USA. Electronic address: Krystof.Bankiewicz@ucsf.edu. · Interventional Neuro Center, Department of Neurological Surgery, University of California San Francisco, San Francisco, CA 94110, USA. ·J Control Release · Pubmed #26924352.

ABSTRACT: Gene transfer technology offers great promise as a potential therapeutic approach to the brain but has to be viewed as a very complex technology. Success of ongoing clinical gene therapy trials depends on many factors such as selection of the correct genetic and anatomical target in the brain. In addition, selection of the viral vector capable of transfer of therapeutic gene into target cells, along with long-term expression that avoids immunotoxicity has to be established. As with any drug development strategy, delivery of gene therapy has to be consistent and predictable in each study subject. Failed drug and vector delivery will lead to failed clinical trials. In this article, we describe our experience with AAV viral vector delivery system, that allows us to optimize and monitor in real time viral vector administration into affected regions of the brain. In addition to discussing MRI-guided technology for administration of AAV vectors we have developed and now employ in current clinical trials, we also describe ways in which infusion cannula design and stereotactic trajectory may be used to maximize the anatomical coverage by using fluid backflow. This innovative approach enables more precise coverage by fitting the shape of the infusion to the shape of the anatomical target.

22 Review Epigenetic Treatment of Neurodegenerative Disorders: Alzheimer and Parkinson Diseases. 2016

Irwin, Michael H / Moos, Walter H / Faller, Douglas V / Steliou, Kosta / Pinkert, Carl A. ·Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA. · Department of Pharmaceutical Chemistry, School of Pharmacy, University of California San Francisco, San Francisco, CA, USA. · SRI Biosciences, A Division of SRI International, Menlo Park, CA, USA. · Cancer Research Center, Boston University School of Medicine, Boston, MA, USA. · PhenoMatriX, Inc., Boston, MA, USA. · Department of Biological Sciences, College of Arts and Sciences, The University of Alabama, Tuscaloosa, AL, USA. ·Drug Dev Res · Pubmed #26899010.

ABSTRACT: Preclinical Research In this review, we discuss epigenetic-driven methods for treating neurodegenerative disorders associated with mitochondrial dysfunction, focusing on carnitinoid antioxidant-histone deacetylase inhibitors that show an ability to reinvigorate synaptic plasticity and protect against neuromotor decline in vivo. Aging remains a major risk factor in patients who progress to dementia, a clinical syndrome typified by decreased mental capacity, including impairments in memory, language skills, and executive function. Energy metabolism and mitochondrial dysfunction are viewed as determinants in the aging process that may afford therapeutic targets for a host of disease conditions, the brain being primary in such thinking. Mitochondrial dysfunction is a core feature in the pathophysiology of both Alzheimer and Parkinson diseases and rare mitochondrial diseases. The potential of new therapies in this area extends to glaucoma and other ophthalmic disorders, migraine, Creutzfeldt-Jakob disease, post-traumatic stress disorder, systemic exertion intolerance disease, and chemotherapy-induced cognitive impairment. An emerging and hopefully more promising approach to addressing these hard-to-treat diseases leverages their sensitivity to activation of master regulators of antioxidant and cytoprotective genes, antioxidant response elements, and mitophagy. Drug Dev Res 77 : 109-123, 2016. © 2016 Wiley Periodicals, Inc.

23 Review Dopaminergic Neurons and Brain Reward Pathways: From Neurogenesis to Circuit Assembly. 2016

Luo, Sarah X / Huang, Eric J. ·Neuroscience Graduate Program, University of California San Francisco, San Francisco, California; Department of Pathology, University of California San Francisco, San Francisco, California. · Neuroscience Graduate Program, University of California San Francisco, San Francisco, California; Department of Pathology, University of California San Francisco, San Francisco, California; Pathology Service 113B, San Francisco Veterans Affairs Medical Center, San Francisco, California. Electronic address: eric.huang2@ucsf.edu. ·Am J Pathol · Pubmed #26724386.

ABSTRACT: Midbrain dopaminergic (DA) neurons in the substantia nigra pars compacta and ventral tegmental area regulate extrapyramidal movement and important cognitive functions, including motivation, reward associations, and habit learning. Dysfunctions in DA neuron circuitry have been implicated in several neuropsychiatric disorders, including addiction and schizophrenia, whereas selective degeneration of DA neurons in substantia nigra pars compacta is a key neuropathological feature in Parkinson disease. Efforts to understand these disorders have focused on dissecting the underlying causes, as well as developing therapeutic strategies to replenish dopamine deficiency. In particular, the promise of cell replacement therapies for clinical intervention has led to extensive research in the identification of mechanisms involved in DA neuron development. It is hoped that a comprehensive understanding of these mechanisms will lead to therapeutic strategies that improve the efficiency of DA neuron production, engraftment, and function. This review provides a comprehensive discussion on how Wnt/β-catenin and sonic hedgehog-Smoothened signaling mechanisms control the specification and expansion of DA progenitors and the differentiation of DA neurons. We also discuss how mechanisms involving transforming growth factor-β and transcriptional cofactor homeodomain interacting protein kinase 2 regulate the survival and maturation of DA neurons in early postnatal life. These results not only reveal fundamental mechanisms regulating DA neuron development, but also provide important insights to their potential contributions to neuropsychiatric and neurodegenerative diseases.

24 Review Repetitive Transcranial Magnetic Stimulation (rTMS) Therapy in Parkinson Disease: A Meta-Analysis. 2016

Wagle Shukla, Aparna / Shuster, Jonathan J / Chung, Jae Woo / Vaillancourt, David E / Patten, Carolynn / Ostrem, Jill / Okun, Michael S. ·Department of Neurology and Center for Movement Disorders and Neurorestoration, University of Florida, 3450 Hull Road, Gainesville, FL 32607(∗). Electronic address: aparna.shukla@neurology.ufl.edu. · Department of Health Outcomes and Policy, Clinical and Translational Science Institute, University of Florida, Gainesville, FL(†). · Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL(‡). · Department of Neurology and Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, FL; Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL(§). · Brain Rehabilitation Research Center of Excellence and Department of Physical Therapy, University of Florida, Gainesville, FL(‖). · Department of Neurology and Surgical Movement Disorders, University of California, San Francisco, CA(¶). · Department of Neurology and Center for Movement Disorders and Neurorestoration, University of Florida, Gainesville, FL(#). ·PM R · Pubmed #26314233.

ABSTRACT: OBJECTIVE: Several studies have reported repetitive transcranial magnetic stimulation (rTMS) therapy as an effective treatment for the control of motor symptoms in Parkinson disease. The objective of the study is to quantify the overall efficacy of this treatment. TYPES: Systematic review and meta-analysis. LITERATURE SURVEY: We reviewed the literature on clinical rTMS trials in Parkinson disease since the technique was introduced in 1980. We used the following databases: MEDLINE, Web of Science, Cochrane, and CINAHL. PATIENTS AND SETTING: Patients with Parkinson disease who were participating in prospective clinical trials that included an active arm and a control arm and change in motor scores on Unified Parkinson's Disease Rating Scale as the primary outcome. We pooled data from 21 studies that met these criteria. We then analyzed separately the effects of low- and high-frequency rTMS on clinical motor improvements. SYNTHESIS: The overall pooled mean difference between treatment and control groups in the Unified Parkinson's Disease Rating Scale motor score was significant (4.0 points, 95% confidence interval, 1.5, 6.7; P = .005). rTMS therapy was effective when low-frequency stimulation (≤ 1 Hz) was used with a pooled mean difference of 3.3 points (95% confidence interval 1.6, 5.0; P = .005). There was a trend for significance when high-frequency stimulation (≥ 5 Hz) studies were evaluated with a pooled mean difference of 3.9 points (95% confidence interval, -0.7, 8.5; P = .08). rTMS therapy demonstrated benefits at short-term follow-up (immediately after a treatment protocol) with a pooled mean difference of 3.4 points (95% confidence interval, 0.3, 6.6; P = .03) as well as at long-term follow-up (average follow-up 6 weeks) with mean difference of 4.1 points (95% confidence interval, -0.15, 8.4; P = .05). There were insufficient data to statistically analyze the effects of rTMS when we specifically examined bradykinesia, gait, and levodopa-induced dyskinesia using quantitative methods. CONCLUSION: rTMS therapy in patients with Parkinson disease results in mild-to-moderate motor improvements and has the potential to be used as an adjunct therapy for the treatment of Parkinson disease. Future large, sample studies should be designed to isolate the specific clinical features of Parkinson disease that respond well to rTMS therapy.

25 Review Lewy body dementias. 2015

Walker, Zuzana / Possin, Katherine L / Boeve, Bradley F / Aarsland, Dag. ·Division of Psychiatry, University College London, London, UK; North Essex Partnership University NHS Foundation Trust, Epping, UK. Electronic address: z.walker@ucl.ac.uk. · University of California, San Francisco School of Medicine, San Francisco, CA, USA. · Division of Behavioral Neurology, Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN, USA; Division of Movement Disorders, Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN, USA; Center for Sleep Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA. · Centre for Age-Related Diseases, Stavanger University Hospital, Stavanger, Norway; Department of Geriatric Psychiatry, Akershus University Hospital, Oslo, Norway; Department of Neurobiology, Care Sciences and Society, Division of Alzheimer's Disease Research Centre, Karolinska Institute, Stockholm, Sweden. ·Lancet · Pubmed #26595642.

ABSTRACT: The broad importance of dementia is undisputed, with Alzheimer's disease justifiably getting the most attention. However, dementia with Lewy bodies and Parkinson's disease dementia, now called Lewy body dementias, are the second most common type of degenerative dementia in patients older than 65 years. Despite this, Lewy body dementias receive little attention and patients are often misdiagnosed, leading to less than ideal management. Over the past 10 years, considerable effort has gone into improving diagnostic accuracy by refining diagnostic criteria and using imaging and other biomarkers. Dementia with Lewy bodies and Parkinson's disease dementia share the same pathophysiology, and effective treatments will depend not only on successful treatment of symptoms but also on targeting the pathological mechanisms of disease, ideally before symptoms and clinical signs develop. We summarise the most pertinent progress from the past 10 years, outlining some of the challenges for the future, which will require refinement of diagnosis and clarification of the pathogenesis, leading to disease-modifying treatments.

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