Anne-Katrin Giese1, Markus D Schirmer1, Adrian V Dalca1, Ramesh Sridharan1, Kathleen L Donahue1, Marco Nardin1, Robert Irie1, Elissa C McIntosh1, Steven J T Mocking1, Huichun Xu1, John W Cole1, Eva Giralt-Steinhauer1, Jordi Jimenez-Conde1, Christina Jern1, Dawn O Kleindorfer1, Robin Lemmens1, Johan Wasselius1, Arne Lindgren1, Tatjana Rundek1, Ralph L Sacco1, Reinhold Schmidt1, Pankaj Sharma1, Agnieszka Slowik1, Vincent Thijs1, Bradford B Worrall1, Daniel Woo1, Steven J Kittner1, Patrick F McArdle1, Braxton D Mitchell1, Jonathan Rosand1, James F Meschia1, Ona Wu1, Polina Golland1, Natalia S Rost. 1. From the Department of Neurology (A.-K.G., M.D.S., K.L.D., M.N., J.R., O.W., N.S.R.), Massachusetts General Hospital, Harvard Medical School, Boston; Program in Medical and Population Genetics (A.K.-G, J.R.), Broad Institute of MIT and Harvard; Computer Science and Artificial Intelligence Lab (M.D.S., A.V.D., R. Sridharan, P.G.), Massachusetts Institute of Technology, Cambridge; Department of Population Health Sciences (M.D.S.), German Centre for Neurodegenerative Diseases, Bonn, Germany; Athinoula A. Martinos Center for Biomedical Imaging (A.V.D., R.I., E.C.M., S.J.T.M., J.R., O.W.), Department of Radiology, Massachusetts General Hospital, Charlestown; Division of Endocrinology, Diabetes and Nutrition (H.X., P.F.M., B.D.M.), Department of Medicine, University of Maryland School of Medicine; Department of Neurology (J.W.C., S.J.K.), University of Maryland School of Medicine and Veterans Affairs Maryland Health Care System, Baltimore; Department of Neurology (E.G.-S., J.J.-C.), Neurovascular Research Group, IMIM-Hospital del Mar (Institut Hospital del Mar d'Investigacions Mèdiques), Universitat Autonoma de Barcelona, Spain; Institute of Biomedicine (C.J.), Sahlgrenska Academy at University of Gothenburg, Sweden; Department of Neurology and Rehabilitation Medicine (D.O.K., D.W.), University of Cincinnati College of Medicine, OH; KU Leuven-University of Leuven (R.L.), Department of Neurosciences, Experimental Neurology; VIB (R.L.), Vesalius Research Center, Laboratory of Neurobiology, University Hospitals Leuven, Department of Neurology, Belgium; Department of Clinical Sciences Lund (J.W., A.L.), Neurology, Lund University; Department of Neurology and Rehabilitation Medicine (A.L.), Neurology, Skåne University Hospital, Lund, Sweden; Department of Neurology (T.R., R.L.S.), Miller School of Medicine, University of Miami, The Evelyn F. McKnight Brain Institute, FL; Department of Neurology (R. Schmidt), Clinical Division of Neurogeriatrics, Medical University Graz, Austria; Institute of Cardiovascular Research (P.S.), Royal Holloway University of London, Egham, UK; Ashford and St Peter's Hospital (P.S.), UK; Department of Neurology (A.S.), Jagiellonian University Medical College, Krakow, Poland; Stroke Division (V.T.), Florey Institute of Neuroscience and Mental Health, University of Melbourne Heidelberg; Department of Neurology (V.T.), Austin Health, Heidelberg, Victoria, Australia; Departments of Neurology and Public Health Sciences (B.B.W.), University of Virginia, Charlottesville; Center for Genomic Medicine (J.R.), Massachusetts General Hospital; Henry and Allison McCance Center for Brain Health (J.R.), Boston, MA; and Department of Neurology (J.F.M.), Mayo Clinic, Jacksonville, FL.
Abstract
OBJECTIVE: To examine etiologic stroke subtypes and vascular risk factor profiles and their association with white matter hyperintensity (WMH) burden in patients hospitalized for acute ischemic stroke (AIS). METHODS: For the MRI Genetics Interface Exploration (MRI-GENIE) study, we systematically assembled brain imaging and phenotypic data for 3,301 patients with AIS. All cases underwent standardized web tool-based stroke subtyping with the Causative Classification of Ischemic Stroke (CCS). WMH volume (WMHv) was measured on T2 brain MRI scans of 2,529 patients with a fully automated deep-learning trained algorithm. Univariable and multivariable linear mixed-effects modeling was carried out to investigate the relationship of vascular risk factors with WMHv and CCS subtypes. RESULTS: Patients with AIS with large artery atherosclerosis, major cardioembolic stroke, small artery occlusion (SAO), other, and undetermined causes of AIS differed significantly in their vascular risk factor profile (all p < 0.001). Median WMHv in all patients with AIS was 5.86 cm3 (interquartile range 2.18-14.61 cm3) and differed significantly across CCS subtypes (p < 0.0001). In multivariable analysis, age, hypertension, prior stroke, smoking (all p < 0.001), and diabetes mellitus (p = 0.041) were independent predictors of WMHv. When adjusted for confounders, patients with SAO had significantly higher WMHv compared to those with all other stroke subtypes (p < 0.001). CONCLUSION: In this international multicenter, hospital-based cohort of patients with AIS, we demonstrate that vascular risk factor profiles and extent of WMH burden differ by CCS subtype, with the highest lesion burden detected in patients with SAO. These findings further support the small vessel hypothesis of WMH lesions detected on brain MRI of patients with ischemic stroke.
OBJECTIVE: To examine etiologic stroke subtypes and vascular risk factor profiles and their association with white matter hyperintensity (WMH) burden in patients hospitalized for acute ischemic stroke (AIS). METHODS: For the MRI Genetics Interface Exploration (MRI-GENIE) study, we systematically assembled brain imaging and phenotypic data for 3,301 patients with AIS. All cases underwent standardized web tool-based stroke subtyping with the Causative Classification of Ischemic Stroke (CCS). WMH volume (WMHv) was measured on T2 brain MRI scans of 2,529 patients with a fully automated deep-learning trained algorithm. Univariable and multivariable linear mixed-effects modeling was carried out to investigate the relationship of vascular risk factors with WMHv and CCS subtypes. RESULTS:Patients with AIS with large artery atherosclerosis, major cardioembolic stroke, small artery occlusion (SAO), other, and undetermined causes of AIS differed significantly in their vascular risk factor profile (all p < 0.001). Median WMHv in all patients with AIS was 5.86 cm3 (interquartile range 2.18-14.61 cm3) and differed significantly across CCS subtypes (p < 0.0001). In multivariable analysis, age, hypertension, prior stroke, smoking (all p < 0.001), and diabetes mellitus (p = 0.041) were independent predictors of WMHv. When adjusted for confounders, patients with SAO had significantly higher WMHv compared to those with all other stroke subtypes (p < 0.001). CONCLUSION: In this international multicenter, hospital-based cohort of patients with AIS, we demonstrate that vascular risk factor profiles and extent of WMH burden differ by CCS subtype, with the highest lesion burden detected in patients with SAO. These findings further support the small vessel hypothesis of WMH lesions detected on brain MRI of patients with ischemic stroke.
Authors: Anna K Bonkhoff; Sungmin Hong; Martin Bretzner; Markus D Schirmer; Robert W Regenhardt; E Murat Arsava; Kathleen Donahue; Marco Nardin; Adrian Dalca; Anne-Katrin Giese; Mark R Etherton; Brandon L Hancock; Steven J T Mocking; Elissa McIntosh; John Attia; Oscar Benavente; John W Cole; Amanda Donatti; Christoph Griessenauer; Laura Heitsch; Lukas Holmegaard; Katarina Jood; Jordi Jimenez-Conde; Steven Kittner; Robin Lemmens; Christopher Levi; Caitrin W McDonough; James Meschia; Chia-Ling Phuah; Arndt Rolfs; Stefan Ropele; Jonathan Rosand; Jaume Roquer; Tatjana Rundek; Ralph L Sacco; Reinhold Schmidt; Pankaj Sharma; Agnieszka Slowik; Martin Soederholm; Alessandro Sousa; Tara M Stanne; Daniel Strbian; Turgut Tatlisumak; Vincent Thijs; Achala Vagal; Johan Wasselius; Daniel Woo; Ramin Zand; Patrick McArdle; Bradford B Worrall; Christina Jern; Arne G Lindgren; Jane Maguire; Polina Golland; Danilo Bzdok; Ona Wu; Natalia S Rost Journal: Neurology Date: 2022-07-08 Impact factor: 11.800
Authors: Hossein Mohammadian Foroushani; Rajat Dhar; Yasheng Chen; Jenny Gurney; Ali Hamzehloo; Jin-Moo Lee; Daniel S Marcus Journal: Front Neuroinform Date: 2021-06-24 Impact factor: 3.739
Authors: Martin Bretzner; Anna K Bonkhoff; Markus D Schirmer; Sungmin Hong; Adrian V Dalca; Kathleen L Donahue; Anne-Katrin Giese; Mark R Etherton; Pamela M Rist; Marco Nardin; Razvan Marinescu; Clinton Wang; Robert W Regenhardt; Xavier Leclerc; Renaud Lopes; Oscar R Benavente; John W Cole; Amanda Donatti; Christoph J Griessenauer; Laura Heitsch; Lukas Holmegaard; Katarina Jood; Jordi Jimenez-Conde; Steven J Kittner; Robin Lemmens; Christopher R Levi; Patrick F McArdle; Caitrin W McDonough; James F Meschia; Chia-Ling Phuah; Arndt Rolfs; Stefan Ropele; Jonathan Rosand; Jaume Roquer; Tatjana Rundek; Ralph L Sacco; Reinhold Schmidt; Pankaj Sharma; Agnieszka Slowik; Alessandro Sousa; Tara M Stanne; Daniel Strbian; Turgut Tatlisumak; Vincent Thijs; Achala Vagal; Johan Wasselius; Daniel Woo; Ona Wu; Ramin Zand; Bradford B Worrall; Jane M Maguire; Arne Lindgren; Christina Jern; Polina Golland; Grégory Kuchcinski; Natalia S Rost Journal: Front Neurosci Date: 2021-07-12 Impact factor: 4.677