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Parkinson Disease: HELP
Articles from Imperial College
Based on 201 articles published since 2008
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These are the 201 published articles about Parkinson Disease that originated from Imperial College during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8 · 9
1 Editorial Anatomo-functional basis of nonmotor symptoms in Parkinson disease. 2016

Mano, Tadaaki / Britton, Zelie / Britton, Thomas. ·From Gifu University of Medical Science (T.M.), Japan · Imperial College London (Z.B.) · and King's College Hospital (T.B), London, UK. ·Neurology · Pubmed #27856780.

ABSTRACT: -- No abstract --

2 Editorial Antisaccades and executive dysfunction in PD: Two sides of the same coin? 2015

Malhotra, Paresh A / Bronstein, Adolfo M. ·Division of Brain Sciences, Imperial College, Charing Cross Hospital, Fulham Palace Road, London, W6 8RF, United Kingdom. ·Mov Disord · Pubmed #25772724.

ABSTRACT: -- No abstract --

3 Editorial Dyskinesias after neural transplantation in Parkinson's disease: what do we know and what is next? 2010

Politis, Marios. ·Centre for Neuroscience, Medical Research Council, Hammersmith Hospital, Imperial College London, UK. marios.politis@imperial.ac.uk ·BMC Med · Pubmed #21126348.

ABSTRACT: Since the 1980 s, when cell transplantation into the brain as a cure for Parkinson's disease hit the headlines, several patients with Parkinson's disease have received transplantation of cells from aborted fetuses with the aim of replacing the dopamine cells destroyed by the disease. The results in human studies were unpredictable and raised controversy. Some patients showed remarkable improvement, but many of the patients who underwent transplantation experienced serious disabling adverse reactions, putting an end to human trials since the late 1990 s. These side effects consisted of patients' developing troublesome involuntary, uncontrolled movements in the absence of dopaminergic medication, so-called off-phase, graft-induced dyskinesias. Notwithstanding the several mechanisms having been proposed, the pathogenesis of this type of dyskinesias remained unclear and there was no effective treatment. It has been suggested that graft-induced dyskinesias could be related to fiber outgrowth from the graft causing increased dopamine release, that could be related to the failure of grafts to restore a precise distribution of dopaminergic synaptic contacts on host neurons or may also be induced by inflammatory and immune responses around the graft. A recent study, however, hypothesized that an important factor for the development of graft-induced dyskinesias could include the composition of the cell suspension and specifically that a high proportion of serotonergic neurons cografted in these transplants engage in nonphysiological properties such as false transmitter release. The findings from this study showed serotonergic hyperinnervation in the grafted striatum of two patients with Parkinson's disease who exhibited major motor recovery after transplantation with fetal mesencephalic tissue but later developed graft-induced dyskinesias. Moreover, the dyskinesias were significantly attenuated by administration of a serotonin agonist, which activates the inhibitory serotonin autoreceptors and attenuates transmitter release from serotonergic neurons, indicating that graft-induced dyskinesias were caused by the dense serotonergic innervation engaging in false transmitter release. Here the implications of the recent findings for the development of new human trials testing the safety and efficacy of cell transplantation in patients with Parkinson's disease are discussed.

4 Review Molecular Imaging of Neuroinflammation in Idiopathic Parkinson's Disease. 2018

Roussakis, Andreas-Antonios / Piccini, Paola. ·Imperial College London, Hammersmith Hospital, Neurology Imaging Unit, London, United Kingdom. · Imperial College London, Hammersmith Hospital, Neurology Imaging Unit, London, United Kingdom. Electronic address: paola.piccini@imperial.ac.uk. ·Int Rev Neurobiol · Pubmed #30314603.

ABSTRACT: Neuroinflammation is an important aspect of Parkinson's disease. The study of Parkinson's disease neuroinflammation is quite challenging and is accompanied by controversy. To date, molecular imaging studies have been targeting microglia and more recently astrocytes. In this review article, we discuss the findings from key PET studies with tracers specific for the translocator protein (microglia-specific) and novel evidence from the development of astrocyte-specific PET tracers. We also discuss evidence from pathology studies and in the animal model of Parkinson's disease that form the biological background of current and newer PET neuroinflammation tracers. However, findings from PET imaging studies in microglia have so far not been translated in clinical practice, while no PET study has been conducted in Parkinson's disease specifically targeting astrocytes. Research work is currently focused on (a) identifying new molecular targets for the study of neuroinflammation through PET, (b) assessing the state of neuroinflammation in Parkinson's disease with accuracy and reliability, and (c) developing strategies to modulate the underlying processes of neuroinflammation.

5 Review Overcoming the Blood-Brain Barrier: The Role of Nanomaterials in Treating Neurological Diseases. 2018

Furtado, Denzil / Björnmalm, Mattias / Ayton, Scott / Bush, Ashley I / Kempe, Kristian / Caruso, Frank. ·ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and the Department of Chemical Engineering, The University of Melbourne, Parkville, Victoria, 3010, Australia. · Department of Materials, Department of Bioengineering, and the Institute of Biomedical Engineering, Imperial College London, London, SW7 2AZ, UK. · Melbourne Dementia Research Centre, The Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, 3052, Australia. · Cooperative Research Center for Mental Health, Parkville, Victoria, 3052, Australia. · ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, 3052, Australia. ·Adv Mater · Pubmed #30066406.

ABSTRACT: Therapies directed toward the central nervous system remain difficult to translate into improved clinical outcomes. This is largely due to the blood-brain barrier (BBB), arguably the most tightly regulated interface in the human body, which routinely excludes most therapeutics. Advances in the engineering of nanomaterials and their application in biomedicine (i.e., nanomedicine) are enabling new strategies that have the potential to help improve our understanding and treatment of neurological diseases. Herein, the various mechanisms by which therapeutics can be delivered to the brain are examined and key challenges facing translation of this research from benchtop to bedside are highlighted. Following a contextual overview of the BBB anatomy and physiology in both healthy and diseased states, relevant therapeutic strategies for bypassing and crossing the BBB are discussed. The focus here is especially on nanomaterial-based drug delivery systems and the potential of these to overcome the biological challenges imposed by the BBB. Finally, disease-targeting strategies and clearance mechanisms are explored. The objective is to provide the diverse range of researchers active in the field (e.g., material scientists, chemists, engineers, neuroscientists, and clinicians) with an easily accessible guide to the key opportunities and challenges currently facing the nanomaterial-mediated treatment of neurological diseases.

6 Review Review: Revisiting the human cholinergic nucleus of the diagonal band of Broca. 2018

Liu, A K L / Lim, E J / Ahmed, I / Chang, R C-C / Pearce, R K B / Gentleman, S M. ·Neuropathology Unit, Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK. · Department of Eye Pathology, Institute of Ophthalmology, University College London, London, UK. · Laboratory of Neurodegenerative Diseases, LKS Faculty of Medicine, School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong. · State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Pokfulam, Hong Kong. ·Neuropathol Appl Neurobiol · Pubmed #30005126.

ABSTRACT: Although the nucleus of the vertical limb of the diagonal band of Broca (nvlDBB) is the second largest cholinergic nucleus in the basal forebrain, after the nucleus basalis of Meynert, it has not generally been a focus for studies of neurodegenerative disorders. However, the nvlDBB has an important projection to the hippocampus and discrete lesions of the rostral basal forebrain have been shown to disrupt retrieval memory function, a major deficit seen in patients with Lewy body disorders. One reason for its neglect is that the anatomical boundaries of the nvlDBB are ill defined and this area of the brain is not part of routine diagnostic sampling protocols. We have reviewed the history and anatomy of the nvlDBB and now propose guidelines for distinguishing nvlDBB from other neighbouring cholinergic cell groups for standardizing future clinicopathological work. Thorough review of the literature regarding neurodegenerative conditions reveals inconsistent results in terms of cholinergic neuronal loss within the nvlDBB. This is likely to be due to the use of variable neuronal inclusion criteria and omission of cholinergic immunohistochemical markers. Extrapolating from those studies showing a significant nvlDBB neuronal loss in Lewy body dementia, we propose an anatomical and functional connection between the cholinergic component of the nvlDBB (Ch2) and the CA2 subfield in the hippocampus which may be especially vulnerable in Lewy body disorders.

7 Review Order and disorder in the physiological membrane binding of α-synuclein. 2018

Fusco, Giuliana / Sanz-Hernandez, Maximo / De Simone, Alfonso. ·Department of Life Sciences, Imperial College London, South Kensington SW7 2AZ, London, UK. · Department of Life Sciences, Imperial College London, South Kensington SW7 2AZ, London, UK. Electronic address: adesimon@imperial.ac.uk. ·Curr Opin Struct Biol · Pubmed #29100107.

ABSTRACT: α-Synuclein (αS) is a neuronal protein that localises predominantly at the presynaptic terminals, and whose fibrillar aggregates are the major constituents of Lewy bodies in Parkinson's disease. In vivo αS is partitioned between water-soluble and membrane-bound states, and this highly regulated equilibrium influences its biological behaviour under both physiological and pathological conditions. Here we discuss the sequence and structural determinants underlying the transition between the unstructured cytosolic and partially structured membrane-bound states of αS. The balance between order and disorder in this protein system is crucial for the overall regulation of the membrane affinity, the ability to induce the clustering of synaptic vesicles, and the tendency to self assemble into amyloid fibrils at the surface of biological membranes.

8 Review Restorative Strategies in Movement Disorders: the Contribution of Imaging. 2017

Lao-Kaim, Nicholas P / Piccini, Paola / Tai, Yen F. ·Division of Brain Sciences, Charing Cross Hospital, Imperial College London, Fulham Palace Road, London, W6 8RF, UK. · Division of Brain Sciences, Charing Cross Hospital, Imperial College London, Fulham Palace Road, London, W6 8RF, UK. yen.tai@imperial.ac.uk. ·Curr Neurol Neurosci Rep · Pubmed #29094222.

ABSTRACT: PURPOSE OF REVIEW: The purpose of this review was to review the imaging, particularly positron emission tomography (PET), findings in neurorestoration studies in movement disorders, with specific focus on neural transplantation in Parkinson's disease (PD) and Huntington's disease (HD). RECENT FINDINGS: PET findings in PD transplantation studies have shown that graft survival as reflected by increases in dopaminergic PET markers does not necessarily correlate with clinical improvement. PD patients with more denervated ventral striatum and more imbalanced serotonin-to-dopamine ratio in the grafted neurons tended to have worse outcome. In HD transplantation studies, variable graft survival and clinical responses may be related to host inflammatory/immune responses to the grafts. Information gleaned from imaging findings in previous neural transplantation studies has been used to refine study protocol and patient selection in future trials. This includes identifying suitable candidates for transplantation using imaging markers, employing multiple and/or novel PET tracers to better assess graft functions and inflammatory responses to grafts.

9 Review Osteoporosis: A Hidden Nonmotor Face of Parkinson's Disease. 2017

Metta, Vinod / Sanchez, Tamara C / Padmakumar, Chandrasekhara. ·Imperial College Hospitals NHS, London, United Kingdom; University College London, London, United Kingdom. Electronic address: vinod.metta@nhs.net. · Hospital Universitari Germans Trias i Pujol, Barcelona, Spain. · John Hunter Hospital, Newcastle, NSW, Australia. ·Int Rev Neurobiol · Pubmed #28805587.

ABSTRACT: Osteoporosis is a "hidden nonmotor face" of Parkinson's disease and a cause of considerable morbidity in the older general population and in Parkinson's disease patients. Some regard this as a "hidden epidemic." Women are overrepresented and have considerable problems related to osteoporosis. In general osteoporosis leads to reduced mobility aggravating the motor syndrome of PD. The nonmotor aspects and impact of osteoporosis in PD have remained unexplored. Possible nonmotor consequences include a range of pain syndromes related to local pain, fractures, falls, and injuries as well as pathological fractures and radiculopathy. In addition depression, sleep dysfunction, dementia, as well as fear of falling also complicate the clinical picture. Quality of life deteriorates both for the patient and career. Pathways of care do not always include assessments for osteoporosis and needs to become obligatory particularly in older female PD patients. Active management strategies then need to be undertaken for osteoporosis in PD. Related motor and nonmotor consequences also highlight the importance of multidisciplinary treatment in PD particularly when dealing with osteoporosis.

10 Review Action observation in the modification of postural sway and gait: Theory and use in rehabilitation. 2017

Patel, Mitesh. ·Division of Brain Sciences, Imperial College London, Charing Cross Hospital, London, W6 8RF, UK. Electronic address: Mitesh.Patel1@imperial.ac.uk. ·Gait Posture · Pubmed #28772130.

ABSTRACT: The discovery of cortical neurons responsive to both the observation of another individual's movement and one's own physical movement has spurred scientists into utilising this interplay for rehabilitation. The idea that humans can quickly transfer motor programmes or refine existing motor strategies through observation has only recently gained interest in the context of gait rehabilitation but may offer significant promise as an adjunctive therapy to routine balance training. This review is the first dedicated to action observation in postural control or gait in healthy individuals and patients. The traditional use of action observation in rehabilitation is that the observer has to carefully watch pre-recorded or physically performed actions and thereafter imitate them. Using this approach, previous studies have shown improved gait after action observation in stroke, Parkinson's disease and knee or hip replacement patients. In healthy subjects, action observation reduced postural sway from externally induced balance perturbations. Despite this initial evidence, future studies should establish whether patients are instructed to observe the same movement to be trained (i.e., replicate the observed action(s)) or observe a motor error in order to produce postural countermeasures. The best mode of motor transfer from action observation is yet to be fully explored, and may involve observing live motor acts rather than viewing video clips. Given the ease with which action observation training can be applied in the home, it offers a promising, safe and economical approach as an adjunctive therapy to routine balance training.

11 Review Molecular mechanisms of brain-derived neurotrophic factor in neuro-protection: Recent developments. 2017

Zhao, Hailin / Alam, Azeem / San, Chun-Yin / Eguchi, Shiori / Chen, Qian / Lian, Qingquan / Ma, Daqing. ·Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London, UK. · Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London, UK; Department of Anaesthesiology, Southwest Hospital, Third Military Medical University, Chongqing, China. · Department of Anesthesiology, Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, China. Electronic address: lianqingquanmz@163.com. · Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London, UK. Electronic address: d.ma@imperial.ac.uk. ·Brain Res · Pubmed #28396009.

ABSTRACT: Neuronal cell injury, as a consequence of acute or chronic neurological trauma, is a significant cause of mortality around the world. On a molecular level, the condition is characterized by widespread cell death and poor regeneration, which can result in severe morbidity in survivors. Potential therapeutics are of major interest, with a promising candidate being brain-derived neurotrophic factor (BDNF), a ubiquitous agent in the brain which has been associated with neural development and may facilitate protective and regenerative effects following injury. This review summarizes the available information on the potential benefits of BDNF and the molecular mechanisms involved in several pathological conditions, including hypoxic brain injury, stroke, Alzheimer's disease and Parkinson's disease. It further explores the methods in which BDNF can be applied in clinical and therapeutic settings, and the potential challenges to overcome.

12 Review Molecular imaging to track Parkinson's disease and atypical parkinsonisms: New imaging frontiers. 2017

Strafella, Antonio P / Bohnen, Nicolaas I / Perlmutter, Joel S / Eidelberg, David / Pavese, Nicola / Van Eimeren, Thilo / Piccini, Paola / Politis, Marios / Thobois, Stephane / Ceravolo, Roberto / Higuchi, Makoto / Kaasinen, Valtteri / Masellis, Mario / Peralta, M Cecilia / Obeso, Ignacio / Pineda-Pardo, Jose Ángel / Cilia, Roberto / Ballanger, Benedicte / Niethammer, Martin / Stoessl, Jon A / Anonymous5120895. ·Morton and Gloria Shulman Movement Disorder Unit & E.J. Safra Parkinson Disease Program, Neurology Div/Dept. Medicine, Toronto Western Hospital, UHN; Krembil Research Institute, UHN; Research Imaging Centre, Campbell Family Mental Health Research Institute, CAMH, University of Toronto, Ontario, Canada. · University of Michigan & Veterans Administration Medical Center, Ann Arbor, Michigan, USA. · Neurology, Radiology, Neuroscience, Physical Therapy & Occupational Therapy, Washington University in St. Louis, St. Louis, Missouri, USA. · Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, New York, USA. · Newcastle Magnetic Resonance Centre & Positron Emission Tomography Centre, Newcastle University, Campus for Ageing & Vitality, Newcastle upon Tyne, United Kingdom. · Multimodal Neuroimaging Group-Department of Nuclear Medicine Department of Neurology-University of Cologne, Institute of Neuroscience and Medicine, Jülich Research Center, German Center for Neurodegenerative Diseases (DZNE), Germany. · Neurology Imaging Unit, Centre of Neuroinflammation and Neurodegeneration, Division of Brain Sciences, Hammersmith Campus, Imperial College London, United Kingdom. · Neurodegeneration Imaging Group, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom. · Hospices Civils de Lyon, Hopital Neurologique Pierre Wertheimer, Université Lyon 1; CNRS, Centre de Neurosciences Cognitives, UMR, 5229, Lyon, France. · Department of Clinical and Experimental Medicine, Movement Disorders and Parkinson Center, University of Pisa, Italy. · National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan. · Division of Clinical Neurosciences, Turku University Hospital; Department of Neurology, University of Turku; Turku PET Centre, University of Turku, Turku, Finland. · Cognitive & Movement Disorders Clinic, Sunnybrook Health Sciences Centre; Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada. · Movement Disorder and Parkinson's Disease Program, CEMIC University Hospital, Buenos, Aires, Argentina. · Centro Integral de Neurociencias (CINAC), Hospitales Madrid Puerta del Sur & Centro de Investigación Biomédica en Red, Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. · Parkinson Institute, ASST Gaetano Pini-CTO, Milan, Italy. · INSERM, U1028; CNRS, UMR5292; Lyon Neuroscience Research Center, Neuroplasticity & Neuropathology of Olfactory Perception Team, University Lyon, France. · Pacific Parkinson's Research Centre & National Parkinson Foundation Centre of Excellence, University of British Columbia & Vancouver Coastal Health, Vancouver, British, Columbia, Canada. ·Mov Disord · Pubmed #28150432.

ABSTRACT: Molecular imaging has proven to be a powerful tool for investigation of parkinsonian disorders. One current challenge is to identify biomarkers of early changes that may predict the clinical trajectory of parkinsonian disorders. Exciting new tracer developments hold the potential for in vivo markers of underlying pathology. Herein, we provide an overview of molecular imaging advances and how these approaches help us to understand PD and atypical parkinsonisms. © 2016 International Parkinson and Movement Disorder Society.

13 Review The Cellular Diversity of the Pedunculopontine Nucleus: Relevance to Behavior in Health and Aspects of Parkinson's Disease. 2017

Pienaar, Ilse S / Vernon, Anthony / Winn, Philip. ·1 Centre for Neuroinflammation & Neurodegeneration, Division of Brain Sciences, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, Cane Road, London, UK. · 2 Faculty of Health and Life Sciences, Department of Applied Sciences, Northumbria University, Newcastle upon Tyne, UK. · 3 Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. · 4 Institute of Pharmacy & Biomedical Sciences, University of Strathclyde, Glasgow, UK. ·Neuroscientist · Pubmed #27932591.

ABSTRACT: The pedunculopontine nucleus (PPN) is a rostral brainstem structure that has extensive connections with basal ganglia nuclei and the thalamus. Through these the PPN contributes to neural circuits that effect cortical and hippocampal activity. The PPN also has descending connections to nuclei of the pontine and medullary reticular formations, deep cerebellar nuclei, and the spinal cord. Interest in the PPN has increased dramatically since it was first suggested to be a novel target for treating patients with Parkinson's disease who are refractory to medication. However, application of frequency-specific electrical stimulation of the PPN has produced inconsistent results. A central reason for this is that the PPN is not a heterogeneous structure. In this article, we review current knowledge of the neurochemical identity and topographical distribution of neurons within the PPN of both humans and experimental animals, focusing on studies that used neuronally selective targeting strategies to ascertain how the neurochemical heterogeneity of the PPN relates to its diverse functions in relation to movement and cognitive processes. If the therapeutic potential of the PPN is to be realized, it is critical to understand the complex structure-function relationships that exist here.

14 Review Calcium Channel Antagonists as Disease-Modifying Therapy for Parkinson's Disease: Therapeutic Rationale and Current Status. 2016

Swart, Tara / Hurley, Michael J. ·MIT Sloan Executive Education, Cambridge, MA, 02142, USA. · Neuroepidemiology and Ageing Research, School of Public Health, Imperial College London, Burlington Danes Building, Hammersmith Campus, DuCane Road, London, W12 0NN, UK. m.hurley@imperial.ac.uk. ·CNS Drugs · Pubmed #27826740.

ABSTRACT: Parkinson's disease is a disabling hypokinetic neurological movement disorder in which the aetiology is unknown in the majority of cases. Current pharmacological treatments, though effective at restoring movement, are only symptomatic and do nothing to slow disease progression. Electrophysiological, epidemiological and neuropathological studies have implicated Ca

15 Review Comment on: "Levodopa-Carbidopa Intestinal Gel in Patients with Parkinson's Disease: A Systematic Review". 2016

Lambarth, Andrew T. ·Faculty of Medicine, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK. al3212@ic.ac.uk. ·CNS Drugs · Pubmed #27541607.

ABSTRACT: -- No abstract --

16 Review Registration Accuracy of CT/MRI Fusion for Localisation of Deep Brain Stimulation Electrode Position: An Imaging Study and Systematic Review. 2016

Geevarghese, Ruben / O'Gorman Tuura, Ruth / Lumsden, Daniel E / Samuel, Michael / Ashkan, Keyoumars. ·Department of Neurosurgery, Charing Cross Hospital, London, UK. ·Stereotact Funct Neurosurg · Pubmed #27318464.

ABSTRACT: BACKGROUND: Postoperative imaging is essential for verifying electrode location in patients undergoing deep brain stimulation (DBS). MRI offers better visualisation of brain targets, but concerns about adverse events have limited its use. Preoperative stereotactic MRI fused with a postoperative stereotactic CT, demonstrating the electrode position, is now widely used. OBJECTIVES: The aims of this study were to: (1) evaluate the accuracy of image registration using Neuroinspire, and (2) undertake a systematic review of the literature on CT/MRI fusion techniques to ascertain the accuracy of other software packages. METHODS: Twenty patients who underwent bilateral subthalamic nucleus DBS for Parkinson's disease were selected. The postoperative CT was registered and fused with the preoperative MRI using Neuroinspire. The position of each electrode tip was determined in stereotactic coordinates both in the (unfused) postoperative CT and the fused CT/MRI. The difference in tip position was used to evaluate the registration accuracy. RESULTS: The mean error ± SD of CT/MRI fusion using Neuroinspire was 0.25 ± 0.15, 0.33 ± 0.26 and 0.46 ± 0.55 mm in lateral, anteroposterior and vertical axes. A systematic review suggested that CT/MRI registration with Neuroinspire is more accurate than that achieved with other tested CT/MRI fusion algorithms. CONCLUSION: CT/MRI fusion for localisation of electrode placement offers an accurate, reliable and safe modality for assessing electrode location.

17 Review Imaging Systemic Dysfunction in Parkinson's Disease. 2016

Borghammer, Per / Knudsen, Karoline / Brooks, David J. ·Department of Nuclear Medicine & PET Centre, Institute of Clinical Medicine, Aarhus University Hospital, Norrebrogade 44, building 10, DK-8000, Aarhus C, Denmark. perborgh@rm.dk. · Department of Nuclear Medicine & PET Centre, Institute of Clinical Medicine, Aarhus University Hospital, Norrebrogade 44, building 10, DK-8000, Aarhus C, Denmark. · Division of Neuroscience, Department of Medicine, Imperial College London, London, UK. · Division of Neuroscience, Newcastle University, Newcastle upon Tyne, UK. ·Curr Neurol Neurosci Rep · Pubmed #27072951.

ABSTRACT: Parkinson's disease is now widely recognized to be a multisystem disorder affecting the brain and peripheral autonomic nerves. Extensive pathology is present in both the sympathetic and parasympathetic nervous system and the intrinsic gastrointestinal plexuses in patients. Autonomic pathology and symptoms such as constipation can predate the clinical diagnosis by years or decades. Imaging studies have contributed greatly to our understanding of Parkinson's disease but focused primarily on imaging cerebral pathology. However, given the importance of understanding the nature, chronology, and functional consequences of peripheral pathology, there has been renewed interest in imaging peripheral organs in Parkinson's disease. Suitable imaging tools can be divided into two types: radiotracer studies that directly estimate loss of sympathetic or parasympathetic nerve terminals, and imaging modalities to quantitate dysphagia, gastric emptying, esophageal and intestinal transit times, and anorectal dyssynergia. In this review, we summarize current knowledge about peripheral imaging in Parkinson's disease.

18 Review Imaging synucleinopathies. 2016

Brooks, David J / Tambasco, Nicola. ·Dept of Nuclear Medicine, Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark. · Dept of Medicine, Imperial College London, London, United Kingdom. · Division of Neurology, Newcastle University, Newcastle, United Kingdom. · Dept of Neurology, Azienda Ospedaliera e Universitaria di Perugia, Perugia, Italy. ·Mov Disord · Pubmed #26879635.

ABSTRACT: In this review the structural and functional imaging changes associated with the synucleinopathies PD, MSA, and dementias associated with Lewy bodies are reviewed. The role of imaging for supporting differential diagnosis, detecting subclinical disease, and following disease progression is discussed and its potential use for monitoring disease progression is debated. © 2016 International Parkinson and Movement Disorder Society.

19 Review Molecular imaging of dopamine transporters. 2016

Brooks, David J. ·Dept. of Nuclear Medicine, Aarhus University, Denmark; Division of Neuroscience, Imperial College London, UK; Division of Neuroscience, Newcastle University, UK. Electronic address: dbrooks@clin.au.dk. ·Ageing Res Rev · Pubmed #26802555.

ABSTRACT: The dopamine transporter (DAT) is responsible for clearance of dopamine from the synaptic cleft after its release. Imaging DAT availability provides a measure of dopamine terminal function and a method for detecting the striatal dopamine terminal dysfunction present in idiopathic Parkinson's disease (PD) and atypical neurodegenerative parkinsonian disorders such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). DAT imaging with positron emission tomography (PET) or single photon emission computed tomography (SPECT) can be used to support or refute a diagnosis of dopamine deficient parkinsonism in cases where this is unclear and rationalise a trial of dopamine replacement agents as therapy. It can also detect subclinical dopaminergic dysfunction when present in subjects at risk for PD such as relatives of patients, susceptibility gene mutation carriers, and subjects with late onset hyposmia or sleep disorders. The presence of normal DAT availability on imaging can help categorise "subjects without evidence of dopamine deficiency" (SWEDDs) who on occasion mimic PD and include dystonic tremors, drug-induced and psychogenic parkinsonism in their ranks. Reduced levels of baseline striatal DAT availability on PET or SPECT scanning, however, should be regarded as supportive rather than diagnostic of dopamine deficient parkinsonism.

20 Review Environmental risk factors and Parkinson's disease: An umbrella review of meta-analyses. 2016

Bellou, Vanesa / Belbasis, Lazaros / Tzoulaki, Ioanna / Evangelou, Evangelos / Ioannidis, John P A. ·Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece. · Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece; Department of Biostatistics and Epidemiology, Imperial College London, London, UK; MRC-PHE Centre for Environment and Health, Imperial College London, London, UK. · Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece; Department of Biostatistics and Epidemiology, Imperial College London, London, UK. · Department of Medicine, Stanford Prevention Research Center, Stanford, CA, USA; Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA, USA; Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Stanford, CA, USA; Department of Statistics, Stanford University School of Humanities and Sciences, Stanford, CA, USA. Electronic address: jioannid@stanford.edu. ·Parkinsonism Relat Disord · Pubmed #26739246.

ABSTRACT: BACKGROUND: Parkinson's disease is a neurological disorder with complex pathogenesis implicating both environmental and genetic factors. We aimed to summarise the environmental risk factors that have been studied for potential association with Parkinson's disease, assess the presence of diverse biases, and identify the risk factors with the strongest support. METHODS: We searched PubMed from inception to September 18, 2015, to identify systematic reviews and meta-analyses of observational studies that examined associations between environmental factors and Parkinson's disease. For each meta-analysis we estimated the summary effect size by random-effects and fixed-effects models, the 95% confidence interval and the 95% prediction interval. We estimated the between-study heterogeneity expressed by I(2), evidence of small-study effects and evidence of excess significance bias. RESULTS: Overall, 75 unique meta-analyses on different risk factors for Parkinson's disease were examined, covering diverse biomarkers, dietary factors, drugs, medical history or comorbid diseases, exposure to toxic environmental agents and habits. 21 of 75 meta-analyses had results that were significant at p < 0.001 by random-effects. Evidence for an association was convincing (more than 1000 cases, p < 10(-6) by random-effects, not large heterogeneity, 95% prediction interval excluding the null value and absence of hints for small-study effects and excess significance bias) for constipation, and physical activity. CONCLUSION: Many environmental factors have substantial evidence of association with Parkinson's disease, but several, perhaps most, of them may reflect reverse causation, residual confounding, information bias, sponsor conflicts or other caveats.

21 Review Constipation preceding Parkinson's disease: a systematic review and meta-analysis. 2016

Adams-Carr, Kerala L / Bestwick, Jonathan P / Shribman, Samuel / Lees, Andrew / Schrag, Anette / Noyce, Alastair J. ·Charing Cross Hospital, London, UK. · Wolfson Institute of Preventive Medicine, Barts and The London School of Medicine and Dentistry, London, UK. · National Hospital for Neurology and Neurosurgery, London, UK. · Institute of Neurology, University College London, London, UK. ·J Neurol Neurosurg Psychiatry · Pubmed #26345189.

ABSTRACT: OBJECTIVE: To systematically review published literature to estimate the magnitude of association between premorbid constipation and later diagnosis of Parkinson's disease. BACKGROUND: Constipation is a recognised non-motor feature of Parkinson's and has been reported to predate diagnosis in a number of observational studies. METHODS: A systematic review and meta-analysis was carried out following the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) criteria. A literature search was undertaken in December 2014 using PubMed and the search terms 'Parkinson's disease' and 'constipation'. Articles were screened for suitability and reviewed against inclusion and exclusion criteria. Studies were included if they assessed constipation by means of a structured questionnaire or if constipation/drugs used to treat constipation were coded in patient medical records. Data were extracted using a standardised template and effect size estimates combined using a fixed-effects model. Heterogeneity was explored with the I(2) statistic. RESULTS: 9 studies were included in the meta-analysis, with a combined sample size of 741 593 participants. Those with constipation had a pooled OR of 2.27 (95% CI 2.09 to 2.46) for developing subsequent Parkinson's disease compared with those without constipation. Weak evidence for heterogeneity was found (I(2)=18.9%, p=0.282). Restricting analysis to studies assessing constipation more than 10 years prior to Parkinson's disease gave a pooled OR of 2.13 (95% CI 1.78 to 2.56; I(2)=0.0%). CONCLUSIONS: This systematic review and meta-analysis demonstrates that people with constipation are at a higher risk of developing Parkinson's disease compared with those without and that constipation can predate Parkinson's diagnosis by over a decade.

22 Review Neurodegenerative diseases and therapeutic strategies using iron chelators. 2015

Ward, Roberta J / Dexter, David T / Crichton, Robert R. ·Centre for Neuroinflammation & Neurodegeneration, Imperial College London, Hammersmith Hospital Campus, London W120NN, UK; Universite Catholique de Louvain, Louvain-la-Neuve, Belgium. Electronic address: roberta.ward@uclouvain.be. · Centre for Neuroinflammation & Neurodegeneration, Imperial College London, Hammersmith Hospital Campus, London W120NN, UK. · Universite Catholique de Louvain, Louvain-la-Neuve, Belgium. ·J Trace Elem Med Biol · Pubmed #25716300.

ABSTRACT: This review will summarise the current state of our knowledge concerning the involvement of iron in various neurological diseases and the potential of therapy with iron chelators to retard the progression of the disease. We first discuss briefly the role of metal ions in brain function before outlining the way by which transition metal ions, such as iron and copper, can initiate neurodegeneration through the generation of reactive oxygen and nitrogen species. This results in protein misfolding, amyloid production and formation of insoluble protein aggregates which are contained within inclusion bodies. This will activate microglia leading to neuroinflammation. Neuroinflammation plays an important role in the progression of the neurodegenerative diseases, with activated microglia releasing pro-inflammatory cytokines leading to cellular cell loss. The evidence for metal involvement in Parkinson's and Alzheimer's disease as well as Friedreich's ataxia and multiple sclerosis will be presented. Preliminary results from trials of iron chelation therapy in these neurodegenerative diseases will be reviewed.

23 Review Nucleus basalis of Meynert revisited: anatomy, history and differential involvement in Alzheimer's and Parkinson's disease. 2015

Liu, Alan King Lun / Chang, Raymond Chuen-Chung / Pearce, Ronald K B / Gentleman, Steve M. ·Neuropathology Unit, Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK, king.liu09@imperial.ac.uk. ·Acta Neuropathol · Pubmed #25633602.

ABSTRACT: It has been well established that neuronal loss within the cholinergic nucleus basalis of Meynert (nbM) correlates with cognitive decline in dementing disorders such as Alzheimer's disease (AD). Friedrich Lewy first observed his eponymous inclusion bodies in the nbM of postmortem brain tissue from patients with Parkinson's disease (PD) and cell loss in this area can be at least as extensive as that seen in AD. There has been confusion with regard to the terminology and exact localisation of the nbM within the human basal forebrain for decades due to the diffuse and broad structure of this "nucleus". Also, while topographical projections from the nbM have been mapped out in subhuman primates, no direct clinicopathological correlations between subregional nbM and cortical pathology and specific cognitive profile decline have been performed in human tissue. Here, we review the evolution of the term nbM and the importance of standardised nbM sampling for neuropathological studies. Extensive review of the literature suggests that there is a caudorostral pattern of neuronal loss within the nbM in AD brains. However, the findings in PD are less clear due to the limited number of studies performed. Given the differing neuropsychiatric and cognitive deficits in Lewy body-associated dementias (PD dementia and dementia with Lewy bodies) as compared to AD, we hypothesise that a different pattern of neuronal loss will be found in the nbM of Lewy body disease brains. Understanding the functional significance of the subregions of the nbM could prove important in elucidating the pathogenesis of dementia in PD.

24 Review Urocortin--from Parkinson's disease to the skeleton. 2015

Lawrence, K M / Jackson, T R / Jamieson, D / Stevens, A / Owens, G / Sayan, B S / Locke, I C / Townsend, P A. ·Faculty Institute for Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, St Mary's Hospital, Research Floor, Oxford Road, Manchester M13 9WL, UK; Manchester Centre for Cellular Metabolism, FMHS, UoM, M13 9WL, UK. Electronic address: kevin.lawrence@manchester.ac.uk. · Faculty Institute for Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, St Mary's Hospital, Research Floor, Oxford Road, Manchester M13 9WL, UK; Manchester Centre for Cellular Metabolism, FMHS, UoM, M13 9WL, UK. · Faculty of Life Sciences, Michael Smith Building, University of Manchester, M13 9WL, UK; Biorelate Ltd, Manchester, UK. · Faculty of Medical and Human Sciences, University of Manchester and Royal Manchester Children's Hospital, Manchester M13 9WL, UK. · Department of Biomedical Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK. ·Int J Biochem Cell Biol · Pubmed #25541373.

ABSTRACT: Urocortin (Ucn 1), a 40 amino acid long peptide related to corticotropin releasing factor (CRF) was discovered 19 years ago, based on its sequence homology to the parent molecule. Its existence was inferred in the CNS because of anatomical and pharmacological discrepancies between CRF and its two receptor subtypes. Although originally found in the brain, where it has opposing actions to CRF and therefore confers stress-coping mechanisms, Ucn 1 has subsequently been found throughout the periphery including heart, lung, skin, and immune cells. It is now well established that this small peptide is involved in a multitude of physiological and pathophysiological processes, due to its receptor subtype distribution and promiscuity in second messenger signalling pathways. As a result of extensive studies in this field, there are now well over one thousand peer reviewed publications involving Ucn 1. In this review, we intend to highlight some of the less well known actions of Ucn 1 and in particular its role in neuronal cell protection and maintenance of the skeletal system, both by conventional methods of reviewing the literature and using bioinformatics, to highlight further associations between Ucn 1 and disease conditions. Understanding how Ucn 1 works in these tissues, will help to unravel its role in normal and pathophysiological processes. This would ultimately allow the generation of putative medical interventions for the alleviation of important diseases such as Parkinson's disease, arthritis, and osteoporosis.

25 Review Neuroinflammation in Parkinson's disease: role in neurodegeneration and tissue repair. 2015

Vivekanantham, Sayinthen / Shah, Savan / Dewji, Rizwan / Dewji, Abbas / Khatri, Chetan / Ologunde, Rele. ·a Imperial College School of Medicine, Imperial College London, Exhibition Road, London , United Kingdom. ·Int J Neurosci · Pubmed #25364880.

ABSTRACT: Neuroinflammation in Parkinson's disease [PD] is a process that occurs alongside the loss of dopaminergic neurons, and is associated with alterations to many cell types, most notably microglia. This review examines the key evidence contributing to our understanding of the role of inflammation-mediated degeneration of the dopaminergic (DA) nigrostriatal pathway in PD. It will consider the potential role inflammation plays in tissue repair within the brain, inflammation linked gene products that are associated with sporadic Parkinsonian phenotypes (alpha-synuclein, Parkin and Nurr 1), and developing anti-inflammatory drug treatments in PD. With growing evidence supporting the key role of neuroinflammation in PD pathogenesis, new molecular targets are being found that could potentially prevent or delay nigrostriatal DA neuron loss. Hence, this creates the opportunity for disease modifying treatment, to currently what is an incurable disease.

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