Show simple item record

dc.contributor.advisorWardlaw, Joanna
dc.contributor.advisorDennis, Martin
dc.contributor.authorMakin, Stephen David James
dc.date.accessioned2017-09-22T14:48:19Z
dc.date.available2017-09-22T14:48:19Z
dc.date.issued2017-07-08
dc.identifier.urihttp://hdl.handle.net/1842/23590
dc.description.abstractIntroduction 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 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.en
dc.language.isoenen
dc.publisherThe University of Edinburghen
dc.relation.hasversionMakin 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.en
dc.relation.hasversionMakin 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.en
dc.relation.hasversionMakin 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.en
dc.relation.hasversionDel 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):3000-3006en
dc.relation.hasversionMunoz 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 2016en
dc.relation.hasversionHeye 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.en
dc.relation.hasversionValdes 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.en
dc.relation.hasversionHeye 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 2015en
dc.relation.hasversionStaals 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.en
dc.subjectstrokeen
dc.subjectlacunar strokeen
dc.subjectdietary salten
dc.subjectlesionsen
dc.subjectwhite matteren
dc.titleCauses and consequences of lacunar strokeen
dc.typeThesis or Dissertationen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD Doctor of Philosophyen


Files in this item

This item appears in the following Collection(s)

Show simple item record