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Parkinson Disease: HELP
Articles by Alexander Jon Stoessl
Based on 58 articles published since 2008
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Between 2008 and 2019, A. J. Stoessl wrote the following 58 articles about Parkinson Disease.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Editorial The Saskatchewan Movement Disorders Program: Commitment Pays Off. 2015

Lang, Anthony E / Stoessl, A Jon. · ·Can J Neurol Sci · Pubmed #27482556.

ABSTRACT: -- No abstract --

2 Editorial DAT-SPECT diagnoses dopamine depletion, but not PD. 2014

Stoessl, A Jon / Halliday, Glenda M. ·Pacific Parkinson's Research Centre & National Parkinson Foundation Centre of Excellence, University of British Columbia & Vancouver Coastal Health, Vancouver, BC, Canada. ·Mov Disord · Pubmed #25154601.

ABSTRACT: -- No abstract --

3 Editorial Continuous dopaminergic therapy in Parkinson disease: time to stride back? 2010

Stoessl, A Jon. · ·Ann Neurol · Pubmed #20583222.

ABSTRACT: -- No abstract --

4 Editorial Scans without evidence of dopamine deficiency: the triumph of careful clinical assessment. 2010

Stoessl, A Jon. · ·Mov Disord · Pubmed #20425792.

ABSTRACT: -- No abstract --

5 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.

6 Review Is Axonal Degeneration a Key Early Event in Parkinson's Disease? 2016

Kurowska, Zuzanna / Kordower, Jeffrey H / Stoessl, A Jon / Burke, Robert E / Brundin, Patrik / Yue, Zhenyu / Brady, Scott T / Milbrandt, Jeffrey / Trapp, Bruce D / Sherer, Todd B / Medicetty, Satish. ·Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA. · Renovo Neural Inc., Cleveland, OH, USA. · Research Center for Brain Repair, Rush University Medical Center, Chicago, IL, USA. · Van Andel Research Institute, Center for Neurodegenerative Science, Grand Rapids, MI, USA. · Pacific Parkinson's Research Centre, Division of Neurology and Djavad Mowafaghian Centre for Brain Health, University of British Columbia and Vancouver Coastal Health, BC, Canada. · Departments of Neurology and Pathology & Cell Biology, Columbia University Medical Center, New York City, NY, USA. · Departments of Neurology and Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. · Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL, USA; Marine Biological Laboratory, Woods Hole, MA, USA. · Department of Genetics, Washington University School of Medicine in St. Louis, St. Louis, MO, USA; Hope Center for Neurological Disorders, Washington University School of Medicine in St. Louis, St. Louis, MO, USA. · The Michael J. Fox Foundation for Parkinson's Research, New York, NY, USA. ·J Parkinsons Dis · Pubmed #27497486.

ABSTRACT: Recent research suggests that in Parkinson's disease the long, thin and unmyelinated axons of dopaminergic neurons degenerate early in the disease process. We organized a workshop entitled 'Axonal Pathology in Parkinson's disease', on March 23rd, 2016, in Cleveland, Ohio with the goals of summarizing the state-of-the-art and defining key gaps in knowledge. A group of eight research leaders discussed new developments in clinical pathology, functional imaging, animal models, and mechanisms of degeneration including neuroinflammation, autophagy and axonal transport deficits. While the workshop focused on PD, comparisons were made to other neurological conditions where axonal degeneration is well recognized.

7 Review The role of biomarkers and imaging in Parkinson's disease. 2016

Algarni, Musleh A / Stoessl, A Jon. ·a Pacific Parkinson's Research Centre , University of British Columbia , Vancouver , Canada. · b Department of Medicine , Al Thagher General Hospital , Jeddah , Saudi Arabia. ·Expert Rev Neurother · Pubmed #26829357.

ABSTRACT: The diagnosis of Parkinson's disease (PD) currently relies on the appearance of certain clinical features. However, these features appear only years after the loss of nigral dopaminergic neurons. The progression of PD may be measured using clinical rating scales that are subjective and that have a variable inter-rater consistency. There is a growing need for a biomarker that will allow for early detection of the disease as well as provide a measure of disease progression. In this article, we review different biomarkers, with a focus on functional imaging techniques, which while imperfect, currently provide the best approach to this problem. We also discuss the use of structural imaging and emerging progress in other biochemical and molecular markers. While there is no single biomarker that will satisfy all requirements, a combination is likely to be of great use in identifying those subjects most likely to benefit from neuroprotective therapies, as well as in monitoring the effects of any interventions.

8 Review Optimizing diagnosis in Parkinson's disease: Radionuclide imaging. 2016

Arena, Julieta E / Stoessl, A Jon. ·Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Canada. · Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Canada. Electronic address: jstoessl@mail.ubc.ca. ·Parkinsonism Relat Disord · Pubmed #26439947.

ABSTRACT: Parkinson's disease (PD) and other disorders characterized by basal ganglia dysfunction are often associated with limited structural imaging changes that might assist in the clinical or research setting. Radionuclide imaging has been used to assess characteristic functional changes. Presynaptic dopaminergic dysfunction in PD can be revealed through the imaging of different steps in the process of dopamine synthesis and storage: L-aromatic amino acid decarboxylase (AADC) activity, Vesicular Monoamine Transporter type 2 (VMAT2) binding or its reuptake via the dopamine transporter (DAT). Postsynaptic dopamine dysfunction can also be studied with a variety of different tracers that primarily assess D2-like dopamine receptor availability. The function of other neurotransmitters such as norepinephrine, serotonin and acetylcholine can be imaged as well, giving important information about the underlying pathophysiologic process of PD and its complications. The imaging of metabolic activity and pathologic changes has also provided great advances in the field. Together, these techniques have allowed for a better understanding of PD, may be of aid for differentiating PD from other forms of parkinsonism and will undoubtedly be useful for the establishment of new therapeutic targets.

9 Review Imaging insights into basal ganglia function, Parkinson's disease, and dystonia. 2014

Stoessl, A Jon / Lehericy, Stephane / Strafella, Antonio P. ·Pacific Parkinson's Research Centre and National Parkinson Foundation Centre of Excellence, University of British Columbia and Vancouver Coastal Health, Vancouver, BC, Canada. Electronic address: jstoessl@mail.ubc.ca. · Institut National de la Santé et de la Recherche Médicale, U 1127, F-75013, Paris, France; Centre National de la Recherche Scientifique, Unite Mixte de Recherche 7225, F-75013, Paris, France; Sorbonne Universités, Université Pierre et Marie Curie, Paris 06, Unite Mixte de Recherche S 1127, F-75013, Paris, France; Institut du Cerveau et de la Moelle épinière, ICM (Centre de NeuroImagerie de Recherche, CENIR), F-75013, Paris, France; Assistance Publique, Hopitaux de Paris, Hôpital de la Pitié Salpêtrière, Service de Neuroradiologie F-75013, Paris, France. · Morton and Gloria Shulman Movement Disorder Unit and E J Safra Parkinson Disease Program, University of Toronto, Toronto, ON, Canada; Division of Brain, Imaging and Behaviour-Systems Neuroscience, Toronto Western Hospital and Research Institute, University Health Network, University of Toronto, Toronto, ON, Canada; Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada. ·Lancet · Pubmed #24954673.

ABSTRACT: Recent advances in structural and functional imaging have greatly improved our ability to assess normal functions of the basal ganglia, diagnose parkinsonian syndromes, understand the pathophysiology of parkinsonism and other movement disorders, and detect and monitor disease progression. Radionuclide imaging is the best way to detect and monitor dopamine deficiency, and will probably continue to be the best biomarker for assessment of the effects of disease-modifying therapies. However, advances in magnetic resonance enable the separation of patients with Parkinson's disease from healthy controls, and show great promise for differentiation between Parkinson's disease and other akinetic-rigid syndromes. Radionuclide imaging is useful to show the dopaminergic basis for both motor and behavioural complications of Parkinson's disease and its treatment, and alterations in non-dopaminergic systems. Both PET and MRI can be used to study patterns of functional connectivity in the brain, which is disrupted in Parkinson's disease and in association with its complications, and in other basal-ganglia disorders such as dystonia, in which an anatomical substrate is not otherwise apparent. Functional imaging is increasingly used to assess underlying pathological processes such as neuroinflammation and abnormal protein deposition. This imaging is another promising approach to assess the effects of treatments designed to slow disease progression.

10 Review Developments in neuroimaging: positron emission tomography. 2014

Stoessl, A Jon. ·Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health. Vancouver, Canada. Electronic address: jstoessl@mail.ubc.ca. ·Parkinsonism Relat Disord · Pubmed #24262176.

ABSTRACT: Positron emission tomography (PET) is a powerful technique to quantitatively assess brain function in vivo. In Parkinson's disease (PD), PET can assist in the identification of dopamine deficiency, the characterization of dopamine and other neurotransmitter receptors and transporters, serve as a biomarker and provide insights into motor and non-motor complications of PD. PET can also shed light on mechanisms that underlie disease, such as aberrant protein deposition and neuroinflammation. Emerging developments in multimodal imaging offer the opportunity to study multiple questions concurrently and offer great promise for the future.

11 Review Biomarkers for trials of neuroprotection in Parkinson's disease. 2013

Agarwal, Pankaj A / Stoessl, A Jon. ·Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, British Columbia, Canada. ·Mov Disord · Pubmed #22927101.

ABSTRACT: With increased understanding of disease pathogenesis and the foreseeable reality of disease-modifying therapies, there is a growing need to find biomarkers that will allow early (preferably preclinical) detection of disease and that will provide an independent readout of disease progression. In this article, we review a variety of markers, with a focus on functional imaging techniques, which while imperfect, currently provide the best approach to this problem. We consider the limitations of functional imaging of the dopamine system in assessing the progression of Parkinson's Disease (PD) as well as the potential use of structural imaging and emerging progress in other biochemical and molecular markers. While there is no single biomarker that will satisfy all requirements, some combination is likely to be of great use in identifying those subjects most likely to benefit from neuroprotective therapies, as well as in monitoring the effects of these interventions.

12 Review Neuroimaging: current role in detecting pre-motor Parkinson's disease. 2012

Godau, Jana / Hussl, Anna / Lolekha, Praween / Stoessl, A Jon / Seppi, Klaus. ·Center of Neurology, Hertie Institute for Clinical Brain Research, Department of Neurodegeneration and German Center of Neurodegenerative Diseases (DZNE), University of Tübingen, Tübingen, Germany. ·Mov Disord · Pubmed #22508281.

ABSTRACT: Convergent evidence suggests a pre-motor period in Parkinson's disease (PD) during which typical motor symptoms have not yet developed although dopaminergic neurons in the substantia nigra have started to degenerate. Advances in different neuroimaging techniques have allowed the detection of functional and structural changes in early PD. This review summarizes the state of the art knowledge concerning structural neuroimaging techniques including magnetic resonance imaging (MRI) and transcranial B-mode-Doppler-sonography (TCS) as well as functional neuroimaging techniques using radiotracer imaging (RTI) with different radioligands in detecting pre-motor PD.

13 Review Neuroimaging in Parkinson's disease: from pathology to diagnosis. 2012

Stoessl, A Jon. ·Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, 2221 Wesbrook Mall, Vancouver, BC, Canada. jstoessl@mail.ubc.ca ·Parkinsonism Relat Disord · Pubmed #22166455.

ABSTRACT: Imaging allows a window into the pathology of PD during life, and potentially even prior to the appearance of motor manifestations. Functional imaging using dopaminergic tracers with either PET or SPECT can identify dopamine deficiency but may not reliably differentiate between PD and other akinetic-rigid disorders. On the other hand, dopaminergic tracer imaging can identify pre-motor changes in subjects at high risk of developing PD and may be useful as a biomarker to assess disease progression, with caveats. Glucose or cerebral blood flow imaging can provide complementary information on patterns of cerebral activation and thereby be useful for diagnosis and for the assessment of compensatory strategies. Although traditionally considered to be of limited utility for the study of PD and related disorders, novel magnetic resonance imaging techniques are showing increasing promise for diagnosis and potentially as biomarkers. These applications will be reviewed here, as will the potential use of imaging to assess Braak's hypothesis of caudal to rostral degeneration in vivo.

14 Review Advances in imaging in Parkinson's disease. 2011

Stoessl, A Jon / Martin, Wr Wayne / McKeown, Martin J / Sossi, Vesna. ·Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada. jstoessl@mail.ubc.ca ·Lancet Neurol · Pubmed #22014434.

ABSTRACT: Advances in imaging have made it possible to detect functional and, increasingly, structural changes in Parkinson's disease. Although imaging is not yet routinely used for diagnosis, such an application is becoming increasingly feasible. Of potentially greater interest, however, is the use of imaging as a biomarker to detect premotor disease and disease progression. Imaging also provides insights into complications of Parkinson's disease and its long-term treatment, and the role of dopamine in the normal brain. Furthermore, these techniques can be applied to animal models, to help validate these models and allow their use in the study of potential disease-modifying therapies.

15 Review Neuroimaging in Parkinson's disease. 2011

Stoessl, A Jon. ·Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, British Columbia, Canada. jstoessl@interchange.ubc.ca ·Neurotherapeutics · Pubmed #21274687.

ABSTRACT: Parkinson's disease (PD) is a common disorder in which the primary features can be related to dopamine deficiency. Changes on structural imaging are limited, but a wealth of abnormalities can be detected using positron emission tomography, single photon emission computed tomography, or functional magnetic resonance imaging to detect changes in neurochemical pathology or functional connectivity. The changes detected on these studies may reflect the disease process itself and/or compensatory responses to the disease, or they may arise in association with disease- and/or treatment-related complications. This review will focus mainly on neurochemical and metabolic studies and reviews various approaches to the assessment of dopaminergic function as well as the function of other neurotransmitters that may be affected in PD. A number of clinical applications are highlighted, including diagnostic utility, identification of preclinical disease, changes associated with motor and nonmotor complications of PD, and the effects of various therapeutic interventions.

16 Review Imaging the nigrostriatal system to monitor disease progression and treatment-induced complications. 2010

Kuriakose, Renju / Stoessl, A Jon. ·Pacific Parkinson’s Research Centre, University of British Columbia and Vancouver Coastal Health, Vancouver, BC, Canada. ·Prog Brain Res · Pubmed #20887875.

ABSTRACT: Radiotracer imaging (RTI) techniques such as positron emission tomography (PET) allow the in vivo assessment of nigrostriatal DA function in Parkinson's disease and have provided valuable insights into the mechanisms of nigrostriatal degeneration and the consequent compensatory changes. Moreover, functional imaging serves as an excellent tool in the assessment of the progression of PD and the evolution of treatment-related complications. However, various studies have shown discordance between clinical progression of PD and nigrostriatal degeneration estimated by PET or SPECT, and no RTI technique can be reliably used as a biomarker for progression of PD. Presynaptic dopaminergic imaging has consistently demonstrated an anterior-posterior gradient of dopaminergic dysfunction predominantly affecting the putamen, with side-to-side asymmetry in tracer binding. Dopaminergic hypofunction in the striatum follows a negative exponential pattern with the fastest rate of decline in early disease. Evaluation of central pharmacokinetics of levodopa action by PET has demonstrated the role of increased synaptic dopamine turnover and downregulation of the dopamine transporter in the pathophysiology of levodopa-induced dyskinesias. In PD with behavioral complications such as impulse control disorders, increased levels of dopamine release have been observed in the ventral striatum during performance of a positive reward task, as well as loss of deactivation in orbitofrontal cortex in response to negative reward prediction errors. This suggests that there is a pathologically heightened "reward" response in the ventral striatum together with loss of the capacity to respond to negative outcomes. Overall, functional imaging with PET is an excellent tool for understanding the disease and its complications; however, caution must be applied in interpretation of the results.

17 Review Parkin and Parkinson's disease: differentiated by non-dopaminergic dysfunction? 2010

Stoessl, A Jon. ·Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, 2221 Wesbrook Mall, Vancouver, BC Canada V6T 2B5. ·Exp Neurol · Pubmed #20450912.

ABSTRACT: -- No abstract --

18 Review Functional imaging studies of non-motoric manifestations of Parkinson's Disease. 2009

Stoessl, A Jon. ·Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC, Canada. jstoessl@interchange.ubc.ca ·Parkinsonism Relat Disord · Pubmed #20082973.

ABSTRACT: Positron emission tomography has been widely exploited to study the progression of Parkinson's disease (PD) and the associated motor impairment. It is however now increasingly appreciated that much of the disability of PD arises from non-motor complications, including cognitive and behavioural problems, sleep disturbances, pain and autonomic dysfunction. Recent studies in which these problems were investigated are reviewed in this paper. Although interesting findings are emerging, much work remains to be done. This will depend upon the ability to investigate non dopaminergic mechanisms as well as extra-striatal release of dopamine and the capacity to assess the impact of behaviourally relevant stimuli on neurotransmitter release and on networks of brain activation. Functional imaging studies, including PET, SPECT and functional MRI may provide valuable insights into the pathophysiology of disorders such as Parkinson's disease (PD), where structural changes are limited. Until recently, the major focus of such studies has been either on patterns of cerebral blood flow or glucose metabolism at rest or following a variety of activation paradigms, or on studies of the dopamine (DA) system. This article will review non-motor aspects of PD. While there is an enormous volume of imaging literature on the motor aspects of PD or motoric complications, that will not be addressed here.

19 Review Functional imaging in Parkinson disease. 2008

Nandhagopal, R / McKeown, Martin J / Stoessl, A Jon. ·Pacific Parkinson's Research Center, University of British Columbia, Vancouver Hospital and Health Sciences Center, Purdy Pavilion, 2221 Wesbrook Mall, Vancouver, BC, Canada. ·Neurology · Pubmed #18413571.

ABSTRACT: OBJECTIVE: Functional imaging techniques represent useful tools to assess in vivo the neurochemical alterations and functional connectivity in Parkinson disease (PD). Here, the authors review the various approaches and potential application of these imaging techniques to the study of PD. METHOD: Radiotracer imaging using dopaminergic markers facilitates assessment of pre- and postsynaptic nigrostriatal integrity, while imaging with other appropriate radiotracers explores nondopaminergic neurotransmitter function, local metabolism, blood flow, and mechanisms potentially related to disease progression and pathogenesis. Activation studies using functional MRI detect blood oxygen level dependent signal, as an indirect marker of neuronal activity. RESULT: Functional imaging techniques have been applied to infer the potential role of inflammation and other factors in etiopathogenesis as well as to study compensatory and regulatory mechanisms in early PD and subclinical disease in genetic forms of PD. Imaging studies also help to understand the neurobiological basis of motor and nonmotor complications. Recent reports suggest a role for striatal dopaminergic transmission in modulating neurobehavioral processes including the placebo effect in PD. Although functional imaging has been employed to monitor disease progression, the discordance between clinical outcome and imaging measures after therapeutic interventions precludes their use as surrogate end points in clinical trials. Beyond these limitations and potential challenges, imaging techniques continue to find wide application in the study of PD. CONCLUSION: Functional imaging can provide meaningful insights into mechanisms underlying various aspects of motor and nonmotor dysfunction in Parkinson disease and the role of striatal dopaminergic transmission in behavioral processes beyond motor control. These modalities hold promise to study the preclinical phase and to elucidate further the benefits and complications of surgical interventions and the utility of neuroprotective strategies.

20 Clinical Trial Safety and tolerability of intraputaminal delivery of CERE-120 (adeno-associated virus serotype 2-neurturin) to patients with idiopathic Parkinson's disease: an open-label, phase I trial. 2008

Marks, William J / Ostrem, Jill L / Verhagen, Leonard / Starr, Philip A / Larson, Paul S / Bakay, Roy Ae / Taylor, Robin / Cahn-Weiner, Deborah A / Stoessl, A Jon / Olanow, C Warren / Bartus, Raymond T. ·Department of Neurology, University of California, San Francisco, San Francisco, CA 94143-0138, USA. william.marks@ucsf.edu ·Lancet Neurol · Pubmed #18387850.

ABSTRACT: BACKGROUND: There is an urgent need for therapies that slow or reverse the progression of Parkinson's disease (PD). Neurotrophic factors can improve the function of degenerating neurons and protect against further neurodegeneration, and gene transfer might be a means to deliver effectively these factors to the brain. The aim of this study was to assess the safety, tolerability, and potential efficacy of gene delivery of the neurotrophic factor neurturin. METHODS: In this phase I, open-label clinical trial, 12 patients aged 35-75 years with a diagnosis of PD for at least 5 years in accordance with the UK Brain Bank Criteria received bilateral, stereotactic, intraputaminal injections of adeno-associated virus serotype 2-neurturin (CERE-120). The first six patients received doses of 1.3x10(11) vector genomes (vg)/patient, and the next six patients received 5.4x10(11) vg/patient. This trial is registered with ClinicalTrials.gov, number NCT00252850. FINDINGS: The procedure was well tolerated. Extensive safety monitoring in all patients revealed no clinically significant adverse events at 1 year. Several secondary measures of motor function showed improvement at 1 year; for example, a mean improvement in the off-medication motor subscore of the Unified Parkinson's Disease Rating Scale (UPDRS) of 14 points (SD 8; p=0.000121 [36% mean increase; p=0.000123]) and a mean increase of 2.3 h (2; 25% group mean increase; p=0.0250) in on time without troublesome dyskinesia were seen. Improvements in several secondary measures were not significant, including the timed walking test in the off condition (p=0.053), the Purdue pegboard test of hand dexterity (p=0.318), the reduction in off time (p=0.105), and the activities of daily living subscore (part II) of the UPDRS (p=0.080). (18)F-levodopa-uptake PET did not change after treatment with either dose of CERE-120. INTERPRETATION: The initial data support the safety, tolerability, and potential efficacy of CERE-120 as a possible treatment for PD; however, these results must be viewed as preliminary until data from blinded, controlled clinical trials are available. FUNDING: Ceregene; Michael J Fox Foundation for Parkinson's Research.

21 Article Data-driven, voxel-based analysis of brain PET images: Application of PCA and LASSO methods to visualize and quantify patterns of neurodegeneration. 2018

Klyuzhin, Ivan S / Fu, Jessie F / Hong, Andy / Sacheli, Matthew / Shenkov, Nikolay / Matarazzo, Michele / Rahmim, Arman / Stoessl, A Jon / Sossi, Vesna. ·Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. · Department of Physics and Astronomy, University of British Columbia, Vancouver, British Columbia, Canada. · Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, British Columbia, Canada. · Department of Radiology, Johns Hopkins University, Baltimore, Maryland, United States of America. ·PLoS One · Pubmed #30395576.

ABSTRACT: Spatial patterns of radiotracer binding in positron emission tomography (PET) images may convey information related to the disease topology. However, this information is not captured by the standard PET image analysis that quantifies the mean radiotracer uptake within a region of interest (ROI). On the other hand, spatial analyses that use more advanced radiomic features may be difficult to interpret. Here we propose an alternative data-driven, voxel-based approach to spatial pattern analysis in brain PET, which can be easily interpreted. We apply principal component analysis (PCA) to identify voxel covariance patterns, and optimally combine several patterns using the least absolute shrinkage and selection operator (LASSO). The resulting models predict clinical disease metrics from raw voxel values, allowing for inclusion of clinical covariates. The analysis is performed on high-resolution PET images from healthy controls and subjects affected by Parkinson's disease (PD), acquired with a pre-synaptic and a post-synaptic dopaminergic PET tracer. We demonstrate that PCA identifies robust and tracer-specific binding patterns in sub-cortical brain structures; the patterns evolve as a function of disease progression. Principal component LASSO (PC-LASSO) models of clinical disease metrics achieve higher predictive accuracy compared to the mean tracer binding ratio (BR) alone: the cross-validated test mean squared error of adjusted disease duration (motor impairment score) was 16.3 ± 0.17 years2 (9.7 ± 0.15) with mean BR, versus 14.4 ± 0.18 years2 (8.9 ± 0.16) with PC-LASSO. We interpret the best-performing PC-LASSO models in the spatial sense and discuss them with reference to the PD pathology and somatotopic organization of the striatum. PC-LASSO is thus shown to be a useful method to analyze clinically-relevant tracer binding patterns, and to construct interpretable, imaging-based predictive models of clinical metrics.

22 Article Investigation of serotonergic Parkinson's disease-related covariance pattern using [ 2018

Fu, Jessie Fanglu / Klyuzhin, Ivan / Liu, Shuying / Shahinfard, Elham / Vafai, Nasim / McKenzie, Jessamyn / Neilson, Nicole / Mabrouk, Rostom / Sacheli, Matthew A / Wile, Daryl / McKeown, Martin J / Stoessl, A Jon / Sossi, Vesna. ·Department of Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada. Electronic address: jfu@phas.ubc.ca. · Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada. · Department of Neurobiology, Neurology and Geriatrics, Xuanwu Hospital Capital Medical University, Beijing, China. · Djavad Mowafaghian Centre for Brain Health, Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC, Canada. · Department of Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada. · University of British Columbia, Okanagan Southern Medical Program, Kelowna, BC, Canada. ·Neuroimage Clin · Pubmed #29946508.

ABSTRACT: We used positron emission tomography imaging with [

23 Article The effect of LRRK2 mutations on the cholinergic system in manifest and premanifest stages of Parkinson's disease: a cross-sectional PET study. 2018

Liu, Shu-Ying / Wile, Daryl J / Fu, Jessie Fanglu / Valerio, Jason / Shahinfard, Elham / McCormick, Siobhan / Mabrouk, Rostom / Vafai, Nasim / McKenzie, Jess / Neilson, Nicole / Perez-Soriano, Alexandra / Arena, Julieta E / Cherkasova, Mariya / Chan, Piu / Zhang, Jing / Zabetian, Cyrus P / Aasly, Jan O / Wszolek, Zbigniew K / McKeown, Martin J / Adam, Michael J / Ruth, Thomas J / Schulzer, Michael / Sossi, Vesna / Stoessl, A Jon. ·Djavad Mowafaghian Centre for Brain Health, Pacific Parkinson's Research Centre, University of British Columbia and Vancouver Coastal Health, Vancouver, BC, Canada; Department of Neurobiology, Neurology, and Geriatrics, Xuanwu Hospital Capital Medical University, Beijing, China. · University of British Columbia-Okanagan Southern Medical Program, Kelowna, BC, Canada. · Department of Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada. · Djavad Mowafaghian Centre for Brain Health, Pacific Parkinson's Research Centre, University of British Columbia and Vancouver Coastal Health, Vancouver, BC, Canada. · Department of Neurobiology, Neurology, and Geriatrics, Xuanwu Hospital Capital Medical University, Beijing, China. · Department of Pathology, University of Washington, Seattle, WA, USA. · Veterans Affairs Puget Sound Health Care System and Department of Neurology, University of Washington, Seattle, WA, USA. · Norwegian University of Science and Technology, Trondheim, Norway. · Mayo Clinic, Jacksonville, FL, USA. · Department of Chemistry, University of British Columbia, Vancouver, BC, Canada. · TRIUMF (Tri-University Meson Facility), Vancouver, BC, Canada. · Djavad Mowafaghian Centre for Brain Health, Pacific Parkinson's Research Centre, University of British Columbia and Vancouver Coastal Health, Vancouver, BC, Canada. Electronic address: jstoessl@mail.ubc.ca. ·Lancet Neurol · Pubmed #29456161.

ABSTRACT: BACKGROUND: Markers of neuroinflammation are increased in some patients with LRRK2 Parkinson's disease compared with individuals with idiopathic Parkinson's disease, suggesting possible differences in disease pathogenesis. Previous PET studies have suggested amplified dopamine turnover and preserved serotonergic innervation in LRRK2 mutation carriers. We postulated that patients with LRRK2 mutations might show abnormalities of central cholinergic activity, even before the diagnosis of Parkinson's disease. METHODS: Between June, 2009, and December, 2015, we recruited participants from four movement disorder clinics in Canada, Norway, and the USA. Patients with Parkinson's disease were diagnosed by movement disorder neurologists on the basis of the UK Parkinson's Disease Society Brain Bank criteria. LRRK2 carrier status was confirmed by bidirectional Sanger sequencing. We used the PET tracer N- FINDINGS: We recruited 14 patients with LRRK2 Parkinson's disease, 16 LRRK2 mutation carriers without Parkinson's disease, eight patients with idiopathic Parkinson's disease, and 11 healthy controls. We noted significant between-group differences in rates of acetylcholinesterase hydrolysis in cortical regions (average cortex p=0·009, default mode network-related regions p=0·006, limbic network-related regions p=0·020) and the thalamus (p=0·008). LRRK2 mutation carriers without Parkinson's disease had increased acetylcholinesterase hydrolysis rates compared with healthy controls in the cortex (average cortex, p=0·046). Patients with LRRK2 Parkinson's disease had significantly higher acetylcholinesterase activity in some cortical regions (average cortex p=0·043, default mode network-related regions p=0·021) and the thalamus (thalamus p=0·004) compared with individuals with idiopathic disease. Acetylcholinesterase hydrolysis rates in healthy controls were correlated inversely with age. INTERPRETATION: LRRK2 mutations are associated with significantly increased cholinergic activity in the brain in mutation carriers without Parkinson's disease compared with healthy controls and in LRRK2 mutation carriers with Parkinson's disease compared with individuals with idiopathic disease. Changes in cholinergic activity might represent early and sustained attempts to compensate for LRRK2-related dysfunction, or alteration of acetylcholinesterase in non-neuronal cells. FUNDING: Michael J Fox Foundation, National Institutes of Health, and Pacific Alzheimer Research Foundation.

24 Article Homozygous alpha-synuclein p.A53V in familial Parkinson's disease. 2017

Yoshino, Hiroyo / Hirano, Makito / Stoessl, A Jon / Imamichi, Yoko / Ikeda, Aya / Li, Yuanzhe / Funayama, Manabu / Yamada, Ikuko / Nakamura, Yusaku / Sossi, Vesna / Farrer, Matthew J / Nishioka, Kenya / Hattori, Nobutaka. ·Research Institute for Diseases of Old Age, Graduate School of Medicine, Juntendo University, Tokyo, Japan. · Department of Neurology, Kindai University Sakai Hospital, Sakai, Osaka, Japan. · Pacific Parkinson's Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, British Columbia, Canada. · Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan. · Research Institute for Diseases of Old Age, Graduate School of Medicine, Juntendo University, Tokyo, Japan; Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan. · Department of Physics & Astronomy, University of British Columbia, Vancouver, British Columbia, Canada. · Department of Medical Genetics, Brain Research Centre, University of British Columbia, Vancouver, British Columbia, Canada. · Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan. Electronic address: nishioka@juntendo.ac.jp. · Research Institute for Diseases of Old Age, Graduate School of Medicine, Juntendo University, Tokyo, Japan; Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan. Electronic address: nhattori@juntendo.ac.jp. ·Neurobiol Aging · Pubmed #28666710.

ABSTRACT: We have assessed the frequency of alpha-synuclein (SNCA) mutations in Japanese patients with familial or sporadic Parkinson's disease (PD) and surveyed their associated clinical manifestations. We screened SNCA exon 3 in 988 patients without SNCA multiplications (430 with autosomal dominant PD and 558 with sporadic PD). We detected 1 patient harboring a homozygous SNCA p.A53V substitution albeit with an autosomal dominant pattern of disease inheritance (frequency 2/860 = 0.2%). The proband manifested slow and progressive parkinsonism at 55 years. Later she complicated with cognitive decline and hallucinations. Several of her immediate family members also presented with parkinsonism, cognitive decline, and psychosis. Positron emission tomography imaging of

25 Article Serotonin and dopamine transporter PET changes in the premotor phase of LRRK2 parkinsonism: cross-sectional studies. 2017

Wile, Daryl J / Agarwal, Pankaj A / Schulzer, Michael / Mak, Edwin / Dinelle, Katherine / Shahinfard, Elham / Vafai, Nasim / Hasegawa, Kazuko / Zhang, Jing / McKenzie, Jessamyn / Neilson, Nicole / Strongosky, Audrey / Uitti, Ryan J / Guttman, Mark / Zabetian, Cyrus P / Ding, Yu-Shin / Adam, Mike / Aasly, Jan / Wszolek, Zbigniew K / Farrer, Matthew / Sossi, Vesna / Stoessl, A Jon. ·University of British Columbia, Department of Medicine, Vancouver, BC, Canada. Electronic address: dwile@mail.ubc.ca. · Global Hospitals, Mumbai, India. · Department of Statistics, Vancouver, BC, Canada. · Pacific Parkinson's Research Centre, Vancouver, BC, Canada. · Department of Physics and Astronomy, Vancouver, BC, Canada. · Sagamihara National Hospital, Sagamihara, Japan. · Veterans Affairs Puget Sound Health Care System and Department of Neurology, University of Washington, Seattle, WA, USA. · Mayo Clinic, Jacksonville, FL, USA. · Centre for Movement Disorders, Toronto, ON, Canada. · New York University School of Medicine, New York, NY, USA. · TRIUMF, Vancouver, BC, Canada. · Norwegian University of Science and Technology, Trondheim, Norway. · Department of Medical Genetics, Vancouver, BC, Canada. · University of British Columbia, Department of Medicine, Vancouver, BC, Canada; Pacific Parkinson's Research Centre, Vancouver, BC, Canada. ·Lancet Neurol · Pubmed #28336296.

ABSTRACT: BACKGROUND: People with Parkinson's disease can show premotor neurochemical changes in the dopaminergic and non-dopaminergic systems. Using PET, we assessed whether dopaminergic and serotonin transporter changes are similar in LRRK2 mutation carriers with Parkinson's disease and individuals with sporadic Parkinson's disease, and whether LRRK2 mutation carriers without motor symptoms show PET changes. METHODS: We did two cross-sectional PET studies at the Pacific Parkinson's Research Centre in Vancouver, BC, Canada. We included LRRK2 mutation carriers with or without manifest Parkinson's disease, people with sporadic Parkinson's disease, and age-matched healthy controls, all aged 18 years or older. People with Parkinson's disease were diagnosed by a neurologist with movement disorder training, in accordance with the UK Parkinson's Disease Society Brain Bank criteria. LRRK2 carrier status was confirmed by bidirectional Sanger sequencing. In the first study, LRRK2 mutation carriers with or without manifest Parkinson's disease who were referred for investigation between July, 1999, and January, 2012, were scanned with PET tracers for the membrane dopamine transporter, and dopamine synthesis and storage ( FINDINGS: Between January, 1997, and January, 2012, we obtained data for our first study from 40 LRRK2 mutation carriers, 63 individuals with sporadic Parkinson's disease, and 35 healthy controls. We identified significant group differences in striatal dopamine transporter binding (all age ranges in caudate and putamen, p<0·0001) and INTERPRETATION: Dopaminergic and serotonergic changes progress in a similar fashion in LRRK2 mutation carriers with manifest Parkinson's disease and individuals with sporadic Parkinson's disease, but LRRK2 mutation carriers without manifest Parkinson's disease show increased serotonin transporter binding in the striatum, brainstem, and hypothalamus, possibly reflecting compensatory changes in serotonergic innervation preceding the motor onset of Parkinson's disease. Increased serotonergic innervation might contribute to clinical differences in LRRK2 Parkinson's disease, including the emergence of non-motor symptoms and, potentially, differences in the long-term response to levodopa. FUNDING: Canada Research Chairs, Michael J Fox Foundation, National Institutes of Health, Pacific Alzheimer Research Foundation, Pacific Parkinson's Research Institute, National Research Council of Canada.

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