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Title: Association of Stroke Lesion Pattern and White Matter Hyperintensity Burden With Stroke Severity and Outcome.
Austin Authors: Bonkhoff, Anna K;Hong, Sungmin;Bretzner, Martin;Schirmer, Markus D;Regenhardt, Robert W;Arsava, E Murat;Donahue, Kathleen;Nardin, Marco;Dalca, Adrian;Giese, Anne-Katrin;Etherton, Mark R;Hancock, Brandon L;Mocking, Steven J T;McIntosh, Elissa;Attia, John;Benavente, Oscar;Cole, John W;Donatti, Amanda;Griessenauer, Christoph;Heitsch, Laura;Holmegaard, Lukas;Jood, Katarina;Jimenez-Conde, Jordi;Kittner, Steven;Lemmens, Robin;Levi, Christopher;McDonough, Caitrin W;Meschia, James;Phuah, Chia-Ling;Rolfs, Arndt;Ropele, Stefan;Rosand, Jonathan;Roquer, Jaume;Rundek, Tatjana;Sacco, Ralph L;Schmidt, Reinhold;Sharma, Pankaj;Slowik, Agnieszka;Soederholm, Martin;Sousa, Alessandro;Stanne, Tara M;Strbian, Daniel;Tatlisumak, Turgut;Thijs, Vincent N ;Vagal, Achala;Wasselius, Johan;Woo, Daniel;Zand, Ramin;McArdle, Patrick;Worrall, Bradford B;Jern, Christina;Lindgren, Arne G;Maguire, Jane;Golland, Polina;Bzdok, Danilo;Wu, Ona;Rost, Natalia S
Affiliation: The Florey Institute of Neuroscience and Mental Health..
Department of Neurology, John Hunter Hospital, Newcastle, NSW, Australia..
Hunter Medical Research Institute, Newcastle, New South Wales, Australia..
School of Medicine and Public Health, University of Newcastle, NSW, Australia..
J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Harvard Medical School, Boston..
Univ. Lille, Inserm, CHU Lille, U1171 Â- LilNCog (JPARC) Â- Lille Neurosciences & Cognition, F-59000, Lille, France..
Clinic for Neuroradiology, University Hospital Bonn, Germany..
Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, Boston, USA..
Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany..
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA..
Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, British Columbia, Canada..
Department of Neurosurgery, Geisinger, Danville, PA, USA..
Department of Emergency Medicine, Washington University School of Medicine, St Louis, MO, USA..
Department of Neurology, Neurovascular Research Group (NEUVAS), IMIM-Hospital del Mar (Institut Hospital del Mar dÂ'Investigacions Mèdiques), Universitat Autonoma de Barcelona, Barcelona, Spain..
Department of Neurology, University of Maryland School of Medicine and Veterans Affairs Maryland Health Care System, Baltimore, MD, USA..
KU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease (LIND), Leuven, Belgium..
Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, Gainesville, FL, USA..
Department of Neurology, Mayo Clinic, Jacksonville, FL, USA..
Department of Neurology, Washington University School of Medicine & Barnes-Jewish Hospital, St Louis, MO, USA..
Centogene AG, Rostock, Germany..
Department of Neurology and Evelyn F. McKnight Brain Institute, Miller School of Medicine, University of Miami, Miami, FL, USA..
Department of Neurology, Clinical Division of Neurogeriatrics, Medical University Graz, Graz, Austria..
Institute of Cardiovascular Research, Royal Holloway University of London (ICR2UL), Egham, UK St PeterÂ's and Ashford Hospitals, UK..
Department of Neurology, Jagiellonian University Medical College, Krakow, Poland..
Department of clinical sciences Malmö, Lund University, Sweden; Department of Neurology, Skåne University Hospital, Lund and Malmö, Sweden..
Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, SP, Brazil..
Department of Laboratory Medicine, Institute of Biomedicine, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden..
Department of Neurology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland..
Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden..
Department of Radiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA..
Department of Clinical Sciences Lund, Radiology, Lund University, Sweden..
Department of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA..
Department of Neurology, Geisinger, Danville, PA, USA..
Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA..
Departments of Neurology and Public Health Sciences, University of Virginia, Charlottesville, VA, USA..
Department of Neurology, Skåne University Hospital, Lund, Sweden..
Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, Boston, USA..
Department of Biomedical Engineering, McConnell Brain Imaging Centre, Montreal Neurological Institute, Faculty of Medicine, School of Computer Science, McGill University, Montreal, Canada..
University of Technology Sydney, Sydney, Australia..
Department of Neurosurgery, Christian Doppler Clinic, Paracelsus Medical University, Salzburg, Austria..
VIB, Vesalius Research Center, Laboratory of Neurobiology, University Hospitals Leuven, Department of Neurology, Leuven, Belgium..
Henry and Allison McCance Center for Brain Health, Massachusetts General Hospital, Boston, MA, USA..
School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil..
Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden..
Department of Radiology, Neuroradiology, Skåne University Hospital, Lund, Sweden..
Department of Clinical Sciences Lund, Neurology, Lund University, Lund, Sweden..
Mila - Quebec Artificial Intelligence Institute, Montreal, Canada..
Issue Date: 8-Jul-2022
Date: 2022
Publication information: Neurology 2022; 10.1212/WNL.0000000000200926
Abstract: To examine whether high white matter hyperintensity (WMH) burden is associated with greater stroke severity and worse functional outcomes in lesion pattern-specific ways. MR neuroimaging and National Institutes of Health Stroke Scale data at index stroke, as well as modified Rankin Scale (mRS) at 3-6 months post-stroke were obtained from the MRI-GENIE study of acute ischemic stroke (AIS) patients. Individual WMH volume was automatically derived from FLAIR-images. Stroke lesions were automatically segmented from DWI-images, parcellated into atlas-defined brain regions and further condensed to ten lesion patterns via machine-learning-based dimensionality reduction. Stroke lesion effects on AIS severity and unfavorable outcomes (mRS>2) were modeled within purpose-built Bayesian linear and logistic regression frameworks. Interaction effects between stroke lesions and a high versus low WMH burden were integrated via hierarchical model structures. Models were adjusted for age, age2, sex, total DWI-lesion and WMH volumes, and comorbidities. Data were split into derivation and validation cohorts. A total of 928 patients with AIS contributed to acute stroke severity analyses (age: 64.8(14.5), 40% women), 698 patients to long-term functional outcome analyses (age: 65.9(14.7), 41% women). Stroke severity was mainly explained by lesions focused on bilateral subcortical and left-hemispherically pronounced cortical regions across patients with both a high and low WMH burden. Lesions centered on left-hemispheric insular, opercular and inferior frontal regions and lesions affecting right-hemispheric temporo-parietal regions had more pronounced effects on stroke severity in case of high compared to low WMH burden. Unfavorable outcomes were predominantly explained by lesions in bilateral subcortical regions. In difference to the lesion location-specific WMH effects on stroke severity, higher WMH burden increased the odds of unfavorable outcomes independent of lesion location. Higher WMH burden may be associated with an increased stroke severity in case of stroke lesions involving left-hemispheric insular, opercular and inferior frontal regions (potentially linked to language functions) and right-hemispheric temporo-parietal regions (potentially linked to attention). Our findings suggest that patients with specific constellations of WMH burden and lesion locations may have greater benefits from acute recanalization treatments. Future clinical studies are warranted to systematically assess this assumption and guide more tailored treatment decisions.
DOI: 10.1212/WNL.0000000000200926
ORCID: 0000-0002-7594-4159
Journal: Neurology
PubMed URL: 35803717
PubMed URL:
Type: Journal Article
Subjects: Acute ischemic stroke
Bayesian hierarchical modeling
functional outcomes
lesion patterns
stroke severity
white matter hyperintensities
Appears in Collections:Journal articles

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