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      Stroke subtype, vascular risk factors, and total MRI brain small-vessel disease burden

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      , MD, PhD, , MBChB, , MBChB, PhD, , MBChB, MD, FRCP, , MBChB, MD, FRCR
      Neurology
      Lippincott Williams & Wilkins

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          Abstract

          Objectives:

          In this cross-sectional study, we tested the construct validity of a “total SVD score,” which combines individual MRI features of small-vessel disease (SVD) in one measure, by testing associations with vascular risk factors and stroke subtype.

          Methods:

          We analyzed data from patients with lacunar or nondisabling cortical stroke from 2 prospective stroke studies. Brain MRI was rated for the presence of lacunes, white matter hyperintensities, cerebral microbleeds, and perivascular spaces independently. The presence of each SVD feature was summed in an ordinal “SVD score” (range 0–4). We tested associations with vascular risk factors, stroke subtype, and cerebral atrophy using ordinal regression analysis.

          Results:

          In 461 patients, multivariable analysis found that age (odds ratio [OR] 1.10, 95% confidence interval [CI] 1.08–1.12), male sex (OR 1.58, 95% CI 1.10–2.29), hypertension (OR 1.50, 95% CI 1.02–2.20), smoking (OR 2.81, 95% CI 1.59–3.63), and lacunar stroke subtype (OR 2.45, 95% CI 1.70–3.54) were significantly and independently associated with the total SVD score. The score was not associated with cerebral atrophy.

          Conclusions:

          The total SVD score may provide a more complete estimate of the full impact of SVD on the brain, in a simple and pragmatic way. It could have potential for patient or risk stratification or early efficacy assessment in clinical trials of interventions to prevent SVD progression and may (after further testing) have a useful role in clinical practice.

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          Most cited references20

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          Classification and natural history of clinically identifiable subtypes of cerebral infarction.

          We describe the incidence and natural history of four clinically identifiable subgroups of cerebral infarction in a community-based study of 675 patients with first-ever stroke. Of 543 patients with a cerebral infarct, 92 (17%) had large anterior circulation infarcts with both cortical and subcortical involvement (total anterior circulation infarcts, TACI); 185 (34%) had more restricted and predominantly cortical infarcts (partial anterior circulation infarcts, PACI); 129 (24%) had infarcts clearly associated with the vertebrobasilar arterial territory (posterior circulation infarcts, POCI); and 137 (25%) had infarcts confined to the territory of the deep perforating arteries (lacunar infarcts, LACI). There were striking differences in natural history between the groups. The TACI group had a negligible chance of good functional outcome and mortality was high. More than twice as many deaths were due to the complications of immobility than to direct neurological sequelae of the infarct. Patients in the PACI group were much more likely to have an early recurrent stroke than were patients in other groups. Those in the POCI group were at greater risk of a recurrent stroke later in the first year after the index event but had the best chance of a good functional outcome. Despite the small anatomical size of the infarcts in the LACI group, many patients remained substantially handicapped. The findings have important implications for the planning of stroke treatment trials and suggest that various therapies could be directed specifically at the subgroups.
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            Progression of cerebral small vessel disease in relation to risk factors and cognitive consequences: Rotterdam Scan study.

            Cerebral white matter lesions and lacunar infarcts are small vessel disease-related lesions, which are associated with cognitive decline and dementia. We aimed to assess the relationship between risk factors, effect modifiers, and progression of these lesions. Furthermore, we studied the cognitive consequences of lesion progression. Six hundred sixty-eight people, aged 60 to 90 years, underwent repeated MRI scanning and neuropsychological testing within 3-year follow-up. We rated incident lacunar infarcts and change in periventricular and subcortical white matter lesion severity with a semiquantitative scale. We assessed the relationships between age, sex, baseline lesion load, risk factors, lesion progression, and change in cognitive function by multivariate regression analyses and additional stratified analyses. Baseline lesion load, higher age, high blood pressure, and current smoking were independently associated with progression of white matter lesions. Women had more marked progression of subcortical white matter lesions and incident lacunar infarcts compared with men. Carotid atherosclerosis was associated with incident lacunar infarcts. Higher blood pressure did not contribute to lesion progression in people with already severe lesions at baseline nor in the very old. Lesion progression was associated with a paralleled decline in general cognitive function and in particular with a decreased information processing speed. Higher age, female sex, cigarette smoking, elevated blood pressure, and baseline lesion load were associated with small vessel disease progression. Age and baseline lesion load influenced the risk relations with blood pressure. Progression of small vessel disease was related to a paralleled decline in cognitive function.
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              Clinical correlates of white matter findings on cranial magnetic resonance imaging of 3301 elderly people. The Cardiovascular Health Study.

              Our aim was to identify potential risk factors for and clinical manifestations of white matter findings on cranial MRI in elderly people. Medicare eligibility lists were used to obtain a representative sample of 5888 community-dwelling people aged 65 years or older. Correlates of white matter findings were sought among 3301 participants who underwent MRI scanning and denied a history of stroke or transient ischemic attack. Participants underwent extensive standardized evaluations at baseline and on follow-up, including standard questionnaires, physical examination, multiple blood tests, electrocardiogram, pulmonary function tests, carotid sonography, and M-mode echocardiography. Neuroradiologists graded white matter findings from 0 (none) to 9 (maximal) without clinical information. Many potential risk factors were related to the white matter grade, but in the multivariate model the factors significantly (all P < .01) and independently associated with increased grade were greater age, clinically silent stroke on MRI, higher systolic blood pressure, lower forced expiratory volume in 1 second (FEV1), and income less than $50,000 per year. If excluded, FEV1 was replaced in the model by female sex, history of smoking, and history of physician-diagnosed hypertension at the baseline examination. Many clinical features were correlated with the white matter grade, especially those indicating impaired cognitive and lower extremity function. White matter findings were significantly associated with age, silent stroke, hypertension, FEV1, and income. The white matter findings may not be considered benign because they are associated with impaired cognitive and lower extremity function.
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                Author and article information

                Contributors
                Journal
                Neurology
                Neurology
                neurology
                neur
                neurology
                NEUROLOGY
                Neurology
                Lippincott Williams & Wilkins (Hagerstown, MD )
                0028-3878
                1526-632X
                30 September 2014
                30 September 2014
                : 83
                : 14
                : 1228-1234
                Affiliations
                From the Centre for Clinical Brain Sciences (S.D.J.M., F.N.D., M.S.D., J.M.W.), University of Edinburgh, UK; and Department of Neurology and Cardiovascular Research Institute Maastricht (J.S.), Maastricht University Medical Centre, the Netherlands.
                Author notes
                Correspondence to Dr. Wardlaw: joanna.wardlaw@ 123456ed.ac.uk

                Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. The Article Processing Charge was paid by funding provided by the Wellcome Trust to the University of Edinburgh for open access charges.

                Article
                NEUROLOGY2014573717
                10.1212/WNL.0000000000000837
                4180484
                25165388
                b5abe05f-18c2-4130-8346-2918afa70fc7
                © 2014 American Academy of Neurology

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 23 January 2014
                : 02 May 2014
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