Assignment: Evaluate the Literature Review

Assignment: Evaluate the Literature Review Assignment: Evaluate the Literature Review I need help with evaluate the literature review. I Choose a scholarly peer reviewed dissertation/thesis from database and I evaluate it. Assignment: Evaluate the Literature Review lacunarstroke2017__1_.pdf This thesis has been submitted in fulfilment of the requirements for a postgraduate degree (e.g. PhD, MPhil, DClinPsychol) at the University of Edinburgh. Please note the following terms and conditions of use: This work is protected by copyright and other intellectual property rights, which are retained by the thesis author, unless otherwise stated. A copy can be downloaded for personal non-commercial research or study, without prior permission or charge. This thesis cannot be reproduced or quoted extensively from without first obtaining permission in writing from the author. The content must not be changed in any way or sold commercially in any format or medium without the formal permission of the author. When referring to this work, full bibliographic details including the author, title, awarding institution and date of the thesis must be given. Causes and Consequences of Lacunar Stroke Stephen David James Makin MBChB, MRCP Doctor of Philosophy University of Edinburgh 2017 Declaration I declare that this thesis was composed by me and that the work contained therein is my own except when explicitly stated otherwise in the text. The work within this thesis has not been submitted for any other degree or professional qualification. All figures have been used with permission of Professor Wardlaw, who is attributed in the caption. ii Publications directly related to the results presented in this thesis Makin SD, Turpin S, Dennis MS, Wardlaw JM. Cognitive impairment after lacunar stroke: systematic review and meta-analysis of incidence, prevalence and comparison with other stroke subtypes. J Neurol Neurosurg Psychiatry 2013 August;84(8):893-900. Reproduced in Chapter 2.1 Makin SD, Cook FA, Dennis MS, Wardlaw JM. Cerebral small vessel disease and renal function: systematic review and meta-analysis. Cerebrovasc Dis 2015;39(1):39-52. Reproduced in Chapter 2.2 Makin SD, Doubal FN, Dennis MS, Wardlaw JM. Clinically Confirmed Stroke With Negative Diffusion-Weighted Imaging Magnetic Resonance Imaging: Longitudinal Study of Clinical Outcomes, Stroke Recurrence, and Systematic Review. Stroke 2015 November;46(11):3142-8. Reproduced in Chapter 4.6 Del BA, Makin SDJ, Doubal FN, Inzitari D, Wardlaw JM. Variation in risk factors for recent small subcortical infarcts with infarct size, shape, and location. Stroke 2013;44(11):3000-3006 Reproduced in Chapter 5 – although Dr de Bene is listed as first author I carried out the statistical analysis and extensively re-drafted the text. Assignment: Evaluate the Literature Review I was advised the contribution was extensive enough to consider it as part of my thesis. Four chapters are direct reproductions of these journal articles. As these are articles where I wrote the majority of the text as well as carried out the data analysis I have simply reproduced them in this thesis. I have reformatted the text and tables to fit in with the rest of the thesis layout. Figures which are from other publications have been indicated in the text and are reproduced with the permission of the author. iii Publications arising from the patients recruited in the course of this thesis but where results are not directly reported in this thesis Munoz MS, Chappell FM, Valdes Hernandez MC, Armitage PA, Makin SD, Heye AK, Thrippleton MJ, Sakka E, Shuler K, Dennis MS, Wardlaw JM. Integrity of normal-appearing white matter: Influence of age, visible lesion burden and hypertension in patients with small-vessel disease. J Cereb Blood Flow Metab 2016 Heye AK, Thrippleton MJ, Armitage PA, Valdes Hernandez MC, Makin SD, Glatz A, Sakka E, Wardlaw JM. Tracer kinetic modelling for DCE-MRI quantification of subtle blood-brain barrier permeability. Neuroimage 2016 January 15;125:446-55. Valdes Hernandez MC, Maconick LC, Munoz MS, Wang X, Wiseman S, Armitage PA, Doubal FN, Makin S, Sudlow CL, Dennis MS, Deary IJ, Bastin M, Wardlaw JM. A comparison of location of acute symptomatic vs. ‘silent’ small vessel lesions. Int J Stroke 2015 October;10(7):1044-50. Heye AK, Thrippleton MJ, Chappell FM, Valdes Hernandez MD, Armitage PA, Makin SD, Maniega SM, Sakka E, Flatman PW, Dennis MS, Wardlaw JM. Blood pressure and sodium: association with MRI markers in cerebral small vessel disease. J Cereb Blood Flow Metab 2015 Staals J, Makin SD, Doubal FN, Dennis MS, Wardlaw JM. Stroke subtype, vascular risk factors, and total MRI brain small-vessel disease burden. Neurology 2014 September 30;83(14):1228-34. iv Manuscripts submitted and in preparation Makin SD, Doubal FN, Shuler K, Staals J, Dennis MS, Wardlaw JM. Cognitive impairment is common across ischaemic stroke sub-types, and predicted by premorbid intelligence Submitted to ‘JNNP’ González-Castro V, Valdés Hernández M, Chappell FM, SakkaMakin SD, Armitage PA, Nailon WM Wardlaw JM. Application of texture analysis to the study of the blood-brain barrier in patients with small vessel disease v Acknowledgements This project would never have succeeded without the dedication and teamwork of many people. Above all, I am indebted to the 264 patients and their families for going to so much effort to return to the hospital for MRI scanning and cognitive testing. The stroke clinicians at the Western General Hospital and Stroke Research Network’s Research Nurses identified suitable patients, who were expertly scanned by the radiographers. Professor Ian Deary advised me on the appropriate cognitive tests and Jack Nissan trained me in administering them. Two visiting researchers contributed immensely: Alessandra Del Bene from the University of Florence, who suggested the lesion shape analysis then provided us with the data from Florence; and Julie Staals from The University of Maastricht, who analysed the data from the structural MRI scans. Maria Valdes Hernandez calculated the tissue volumes and Susanna Munoz calculated the FA/MD measurements. Dr. Francesca Chappell extracted the permeability parameters and patiently gave me expert advice on statistics, especially on the analysis of the blood-brain barrier permeability data. Assignment: Evaluate the Literature Review The systematic reviews were ably assisted by: Fabian Cook, then a second-year medical student and now a Foundation year 2 doctor; and Dr. Sarah Turpin, a registrar in medicine for the elderly, who checked my data extraction. I would not have had any data to analyse had Kirsten Shuler not carefully checked the data recorded, flagged up any discrepancies and checked that the cognitive tests were added up correctly. Fergus Doubal, the research fellow on the first Mild Stroke vi Study, kept a close eye on my progress and corrected me if he saw me going astray. Professor Martin Dennis was a constant source of wise advice and experience. The largest credit is due to Professor Joanna Wardlaw, who has tirelessly helped, guided, advised, reviewed, and encouraged. I may not have always been the easiest student to supervise, and she has tirelessly encouraged me to overcome the difficulties we have encountered. And finally, I must thank my wife Ben for her patience and tolerance. vii Abstract Introduction Lacunar strokes are both common and disabling; they cause up to 52 strokes per 100,000 people per year and 29-46% of survivors are disabled. Lacunar stroke is part of the spectrum of small vessel disease (SVD) which also causes cognitive impairment and gait disturbance; together these lead to dementia, falls and disability. Current evidence suggests that SVD is caused by a separate aetiology from large vessel stroke, which may be mediated by blood brain barrier (BBB) permeability and may affect organs other than the brain. We set out to establish whether SVD is a multi-system disorder of primary endothelial function, with leakage of blood-brain barrier leading to lacunar stroke, disability, and cognitive impairment. Methods We recruited 264 patients with a lacunar or cortical stroke (118 lacunar, 146 cortical). All patients received baseline assessment of clinical features, magnetic resonance imaging (MRI), renal function, and assessment of dietary salt. At 1-3 months post-stroke we carried out cognitive testing and contrast MRI to assess blood-brain barrier integrity. We followed patients up at 12 months post-stroke with repeat cognitive testing, MRI, and assessment of disability and recurrent stroke. Results We established that lacunar stroke has a different risk factor profile to cortical stroke, confirming findings from previous cohorts, but adding dietary salt as a risk factor for lacunar stroke and other SVD features. We confirmed that patients with a clinical stroke who did not have a lesion on diffusion-weighted MRI had the same clinical outcomes at 1 year post-stroke as those patients who did have a lesion. We viii established that patients who have a lacunar stroke are at as high a risk of post-stroke cognitive impairment as those with a cortical stroke. We found that blood brain barrier leakage predicted cognitive impairment at one year after lacunar and cortical stroke. We established the rates of disability and cognitive impairment at one-year post-lacunar stroke to estimate the required sample size for future trials. Conclusions Taken together these findings confirm that lacunar stroke is part of a syndrome separate to large vessel stroke and may be mediated through blood brain barrier leakage. Dietary salt is an additional risk factor. The findings support further randomised controlled trials of treatments aimed specifically at lacunar stroke and lifestyle interventions including dietary salt reduction. ix Name of student: Stephen Makin University email: [email protected] Degree sought: P.D. Title of thesis: UUN No. of words in the main text of thesis: Causes and Consequences of Lacunar Stroke S098752 85,005 Insert the lay summary text here – the space will expand as you type. This research looks at the causes and consequences of a lacunar strokes: a type of stroke which causes just over one in six of all strokes. A lacunar stroke effects the very small blood vessels, which supply blood to the white matter (the area deep in the brain that contains long nerve fibres that connect the different parts of the brain together) Because of the way the nerve fibers are grouped together, a small lacunar stroke can cause a lot of damage: e.g. a stroke which is less than 2cm in diameter can cause loss of movement to the whole of one side of the body.Assignment: Evaluate the Literature Review Lacunar strokes are caused by damage to the walls of the small vessels, unlike other strokes which are caused by clots coming from elsewhere. We do not know what causes this damage to the walls of the small blood vessels, but there are several different ideas including high blood pressure, diabetes, inflammation, dietary salt, and leakage of the blood brain barrier. A similar process maybe causing damage in other small blood vessels around the body such as those in the kidney and retina. This thesis contains the results of a study we did in Edinburgh looking at the causes of lacunar stroke: to do this we recruited a group of participants who had recently had a lacunar stroke and compared them to people who had recently had another type of stroke. Each patient had three detailed MRI (magnetic resonance imaging) brain scans to find out the type of stroke, whether there were subtle leaks from the blood vessels in the brain, and how the brain looked a year after a stroke. We also tested our participant’s memory and thinking skills at one month and one year after stroke. . We found that people who had not cut back on salt were less likely to have a lacunar stroke than those who had cut back, but kidney problems were just as common in both types of stroke We looked at the effect that lacunar stroke had on peoples memory and thinking skills. We found that one in three people who had a lacunar stroke had impairments of their memory and thinking (cognitive impairment) similar to those seen in people with dementia. This impairment was just as common as people with other types of stroke. We found that people who were older were more likely to have cognitive impairment than younger people, also that people who had a higher intelligence quotient (IQ) in younger life were less likely to have cognitive impairment after a stroke. We found that leakage across the blood brain barrier increased the risk of cognitive impairment after a lacunar stroke, but not in other types of stroke. We also asked how the participants were doing at a year after their stroke, including whether they had a further stroke, and if they needed help from other people with daily activities. We discussed which outcomes should be considered a ‘negative’ endpoint in a clinical trial, and calculated how big a sample of patients would be needed to detect that a treatment was effective. List of abbreviations ADC – Apparent diffusion coefficient ACA – Anterior cerebral artery ACE-R – Addenbrooke’s Cognitive Examination – Revised AD – Alzheimer’s disease ADAS-Cog – Alzheimer’s Disease Assessment Scale cognitive subscale ADLs – Activities of daily living AF – Atrial Fibrillation ARIC – Atherosclerosis Risk in Communities AVR – arteriole:venule ratio BBB – Blood brain barrier BDI – Beck Depression Inventory BMI – Body mass index BP – Blood pressure BZ – Border zone CADASIL – Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy CABG – Coronary artery bypass graft CCACE – Centre for Cognitive Aging and Cognitive Epidemiology, University of Edinburgh CDR – Clinical Dementia Rating Scale CI – Confidence interval COPD – Chronic obstructive pulmonary disease CRP – C reactive protein CSF – Cerebrospinal fluid CT – Computerised topography DCE-MRI – Dynamic contrast-enhanced magnetic resonance imaging DSM – Diagnostic and Statistical Manual of Mental Disorders DTI – Diffusion tensor imaging DWI – Diffusion weighted imaging DWMH – Deep white matter hyperintensities ECG – Electrocardiogram EFS – Edmonton Frail Scale eGFR – Estimated glomerular filtration rate ESR – Erythrocyte sedimentation rate FA – Fractional anisotropy FFQ – Food frequency questionnaire FLAIR – Fluid attenuated inversion recovery GWAS – Genome wide association study HADS – Hospital Anxiety and Depression Scale ICA – Internal carotid artery ICH – Intracerebral haemorrhage ICV – Intracranial volume IHD – Ischaemic heart disease INR – International normalised ratio IQCODE – Informant Questionnaire on Cognitive Decline in the Elderly ii ISSYS – Investigating Silent Strokes in Hypertensives cohort study LACI – Lacunar anterior circulation infarction LADIS – Leukoaraiosis and DISability Study LBC – Lothian Birth Cohort study LVH – Left ventricular hypertrophy LVSD – Left ventricular systolic dysfunction MA/Cr – Microalbumin/creatinine ratio MCA – Middle cerebral artery MCI – Mild cognitive impairment MCV – Mean cell volume MD – Mean diffusivity MMS-2 – Mild Stroke Study 2 MMSE – Mini-Mental State Examination MoCA – Montreal Cognitive Assessment MoCAE – MoCA equivalent MRI – Magnetic resonance imaging mRS – Modified Rankin Score MS – Multiple sclerosis MSS – Mild Stroke Study Na/Cr – Sodium/creatinine ratio NART – National Adult Reading Test NASCET – North American Symptomatic Carotid Endartectomy Trial NAWM – Normal-appearing white matter NIHSS – Assignment: Evaluate the Literature Review National Institute of Health Stroke Scale iii NINDS – National Institute of Neurological Disorders and Stroke NO – Nitrous oxide NOMAS – Northern Manhattan Study OR – Odds ratio OSCP – Oxfordshire Community Stroke Project PABA – P aminobenzoic acid PACI – Partial anterior circulation infarction PCA – Posterior cerebral artery PET – Positron emission tomography PHQ-9 – Public Health Questionnaire-9 POCI – Posterior circulation infarction PRISMA – Preferred Reporting Items for Systematic Reviews and Meta-Analyses PROSPER – Pravastatin in elderly individuals at risk of vascular disease study PSE – Present State Examination PVS – Perivascular spaces PVWMH – Periventricular white matter hyperintensities QoL – Quality of life R-CAMCOG – Rotterdam Cambridge Cognitive Assessment RCT – Random control trial RIE – Royal Infirmary of Edinburgh ROI – Region of interest RSSI – Recent small sub-cortical infarction iv RUN DMC – Radboud University Nijmegen Diffusion tensor and Magnetic resonance imaging Cohort SCAN – Schedules for Clinical Assessment in Neuropsychiatry SCI – Subjective cognitive impairment SCL-90 – Symptom Checklist-90 SD – Standard deviation SHSPR – Spontaneously hypertensive stroke prone rat SPS3 – Secondary Prevention of Small Subcortical Strokes Trial SSRI – Selective serotonin re-uptake inhibitor SVD – Small vessel disease TIA – Transient ischaemic attack TOAST – Trial of Org 10,172 in Acute Stroke Treatment VAMS – Visual Analogue Mood Scale VCI – Vascular cognitive impairment WGH – Western General Hospital WHO – World Health Organisation WMH – White matter hyperintensities v Table of Contentsi Chapter 1 Introduction …………………………………………………………………………………. 1 Chapter 2 Systematic Reviews …………………………………………………………………….. 61 Chapter 3 Methods for collection of new data…………………………………………….. 118 Chapter 4 Description of cohort ………………………………………………………………… 197 Chapter 5 Variation in risk factors for recent small sub-cortical infarcts, including infarct size, shape and location …………………………………………………… 250 Chapter 6 Results of the cognitive tests ……………………………………………………… 272 Chapter 7 Blood-brain barrier (BBB) leakage and cognition………………………. 346 Chapter 8 Renal Function, SVD and BBB leakage ……………………………………… 373 Chapter 9 Is dietary salt associated with SVD? ………………………………………….. 388 Chapter 10 Clinical findings at one year post-stroke, and estimated sample sizes for clinical trials………………………………………………………………………………………… 403 Chapter 11 Conclusions, implications, and suggestions for future research …. 447 Appendix: PRISMA checklists for systematic reviews in Chapter 2 vi Chapter 1 Introduction This chapter will describe the clinical features and current treatment of lacunar stroke and small vessel disease (SVD) and the evidence for the different proposed causes. What is lacunar stroke and how is it diagnosed? Cerebral small vessel disease (SVD), which causes both lacunar stroke (Figure 1.1) and the background features seen on imaging (including white matter hyperintensities (WMH), lacunes, microbleeds, and perivascular spaces (PVS)) is responsible for a great deal of mortality and morbidity, but the cause is unclear and no specific treatments are available. Stroke is the leading cause of disability in adults and consumes 5% of the healthcare budget; 20% of strokes are lacunar and 25% of lacunar stroke survivors are dependent on others. Lacunar stroke affects around 30,000 people per year in the UK.2 Additionally, background SVD in the absence of symptomatic stroke causes vascular dementia, falls, and disability. Vascular disease is the second commonest cause of dementia. Most lacunar strokes are caused by SVD, whereas other ischaemic stroke subtypes are caused by atheroma of the large vessels or emboli. The cause of SVD is unknown, but various theories have been proposed including chronic hypoperfusion, hypertension, ischemia and blood brain barrier (BBB) permeability. Without knowing the cause of SVD it has been difficult to develop a treatment and currently no specific treatments are available. 1 Lacunar stroke is most accurately diagnosed by assessing both clinical and imaging features. The Oxfordshire Community Stroke Project (OCSP) classi … Assignment: Evaluate the Literature Review Get a 10 % discount on an order above $ 100 Use the following coupon code : NURSING10

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