Isabel C Hostettler1, Ghil Schwarz1, Gareth Ambler1, Duncan Wilson1, Gargi Banerjee1, David J Seiffge1, Clare Shakeshaft1, Surabhika Lunawat1, Hannah Cohen1, Tarek A Yousry1, Rustam Al-Shahi Salman1, Gregory Y H Lip1, Martin M Brown1, Keith W Muir1, Henry Houlden1, Hans Rolf Jäger1, David J Werring2. 1. From the Stroke Research Centre (I.C.H., G.S., D.W., G.B., D.J.S., C.S., S.L., M.M.B., D.J.W.), University College London, Queen Square Institute of Neurology; Department of Neurology (G.S.), Stroke Unit, San Raffaele Hospital, Milan, Italy; Department of Statistical Science (G.A.), University College London, Gower Street, UK; Department of Neurology and Stroke Center (D.J.S.), Inselspital, Bern, Switzerland; Haemostasis Research Unit (H.C.), Department of Haematology, University College London, Chenies Mews; Lysholm Department of Neuroradiology and the Neuroradiological Academic Unit (T.A.Y., H.R.J.), Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, Queen Square, London; Centre for Clinical Brain Sciences (R.A.-S.S.), School of Clinical Sciences, University of Edinburgh; Liverpool Centre for Cardiovascular Science (G.Y.H.L.), Liverpool Heart and Chest Hospital, University of Liverpool; Institute of Neuroscience & Psychology (K.W.M.), University of Glasgow, Queen Elizabeth University Hospital, Glasgow; and Department of Molecular Neuroscience (H.H.), UCL Institute of Neurology and the National Hospital for Neurology and Neurosurgery, Queen Square, London. 2. From the Stroke Research Centre (I.C.H., G.S., D.W., G.B., D.J.S., C.S., S.L., M.M.B., D.J.W.), University College London, Queen Square Institute of Neurology; Department of Neurology (G.S.), Stroke Unit, San Raffaele Hospital, Milan, Italy; Department of Statistical Science (G.A.), University College London, Gower Street, UK; Department of Neurology and Stroke Center (D.J.S.), Inselspital, Bern, Switzerland; Haemostasis Research Unit (H.C.), Department of Haematology, University College London, Chenies Mews; Lysholm Department of Neuroradiology and the Neuroradiological Academic Unit (T.A.Y., H.R.J.), Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, Queen Square, London; Centre for Clinical Brain Sciences (R.A.-S.S.), School of Clinical Sciences, University of Edinburgh; Liverpool Centre for Cardiovascular Science (G.Y.H.L.), Liverpool Heart and Chest Hospital, University of Liverpool; Institute of Neuroscience & Psychology (K.W.M.), University of Glasgow, Queen Elizabeth University Hospital, Glasgow; and Department of Molecular Neuroscience (H.H.), UCL Institute of Neurology and the National Hospital for Neurology and Neurosurgery, Queen Square, London. d.werring@ucl.ac.uk.
Abstract
OBJECTIVE: To determine whether CT-based cerebral small vessel disease (SVD) biomarkers are associated with 6-month functional outcome after intracerebral hemorrhage (ICH) and whether these biomarkers improve the performance of the preexisting ICH prediction score. METHODS: We included 864 patients with acute ICH from a multicenter, hospital-based prospective cohort study. We evaluated CT-based SVD biomarkers (white matter hypodensities [WMH], lacunes, brain atrophy, and a composite SVD burden score) and their associations with poor 6-month functional outcome (modified Rankin Scale score >2). The area under the receiver operating characteristic curve (AUROC) and Hosmer-Lemeshow test were used to assess discrimination and calibration of the ICH score with and without SVD biomarkers. RESULTS: In multivariable models (adjusted for ICH score components), WMH presence (odds ratio [OR] 1.52, 95% confidence interval [CI] 1.12-2.06), cortical atrophy presence (OR 1.80, 95% CI 1.19-2.73), deep atrophy presence (OR 1.66, 95% CI 1.17-2.34), and severe atrophy (either deep or cortical) (OR 1.94, 95% CI 1.36-2.74) were independently associated with poor functional outcome. For the revised ICH score, the AUROC was 0.71 (95% CI 0.68-0.74). Adding SVD markers did not significantly improve ICH score discrimination; for the best model (adding severe atrophy), the AUROC was 0.73 (95% CI 0.69-0.76). These results were confirmed when lobar and nonlobar ICH were considered separately. CONCLUSIONS: The ICH score has acceptable discrimination for predicting 6-month functional outcome after ICH. CT biomarkers of SVD are associated with functional outcome, but adding them does not significantly improve ICH score discrimination. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT02513316.
OBJECTIVE: To determine whether CT-based cerebral small vessel disease (SVD) biomarkers are associated with 6-month functional outcome after intracerebral hemorrhage (ICH) and whether these biomarkers improve the performance of the preexisting ICH prediction score. METHODS: We included 864 patients with acute ICH from a multicenter, hospital-based prospective cohort study. We evaluated CT-based SVD biomarkers (white matter hypodensities [WMH], lacunes, brain atrophy, and a composite SVD burden score) and their associations with poor 6-month functional outcome (modified Rankin Scale score >2). The area under the receiver operating characteristic curve (AUROC) and Hosmer-Lemeshow test were used to assess discrimination and calibration of the ICH score with and without SVD biomarkers. RESULTS: In multivariable models (adjusted for ICH score components), WMH presence (odds ratio [OR] 1.52, 95% confidence interval [CI] 1.12-2.06), cortical atrophy presence (OR 1.80, 95% CI 1.19-2.73), deep atrophy presence (OR 1.66, 95% CI 1.17-2.34), and severe atrophy (either deep or cortical) (OR 1.94, 95% CI 1.36-2.74) were independently associated with poor functional outcome. For the revised ICH score, the AUROC was 0.71 (95% CI 0.68-0.74). Adding SVD markers did not significantly improve ICH score discrimination; for the best model (adding severe atrophy), the AUROC was 0.73 (95% CI 0.69-0.76). These results were confirmed when lobar and nonlobar ICH were considered separately. CONCLUSIONS: The ICH score has acceptable discrimination for predicting 6-month functional outcome after ICH. CT biomarkers of SVD are associated with functional outcome, but adding them does not significantly improve ICH score discrimination. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT02513316.