Excessive White Matter Hyperintensity Increases Susceptibility to Poor Functional Outcomes After Acute Ischemic Stroke

Sungmin Hong, J. Philip Kistler Stroke Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.
Anne-Katrin Giese, Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Markus D. Schirmer, J. Philip Kistler Stroke Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.
Anna K. Bonkhoff, J. Philip Kistler Stroke Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.
Martin Bretzner, J. Philip Kistler Stroke Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.
Pamela Rist, Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States.
Adrian V. Dalca, Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, Boston, MA, United States.
Robert W. Regenhardt, J. Philip Kistler Stroke Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.
Mark R. Etherton, J. Philip Kistler Stroke Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.
Kathleen L. Donahue, J. Philip Kistler Stroke Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.
Marco Nardin, J. Philip Kistler Stroke Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.
Steven J. Mocking, Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, United States.
Elissa C. McIntosh, Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, United States.
John Attia, Hunter Medical Research Institute, Newcastle, NSW, Australia.
Oscar R. Benavente, Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
John W. Cole, Department of Neurology, University of Maryland School of Medicine and Veterans Affairs Maryland Health Care System, Baltimore, MD, United States.
Amanda Donatti, School of Medical Sciences, University of Campinas (UNICAMP) and the Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, Brazil.
Christoph J. Griessenauer, Department of Neurosurgery, Geisinger, Danville, PA, United States.
Laura Heitsch, Division of Emergency Medicine, Washington University School of Medicine, St. Louis, MO, United States.
Lukas Holmegaard, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg and Department of Neurology, The Sahlgrenska University Hospital, Gothenburg, Sweden.
Katarina Jood, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg and Department of Neurology, The Sahlgrenska University Hospital, Gothenburg, Sweden.
Jordi Jimenez-Conde, Department of Neurology, Neurovascular Research Group (NEUVAS), IMIM-Hospital del Mar (Institut Hospital del Mar d'Investigacions M'ediques), Universitat Autonoma de Barcelona, Barcelona, Spain.
Jaume Roquer, Department of Neurology, Neurovascular Research Group (NEUVAS), IMIM-Hospital del Mar (Institut Hospital del Mar d'Investigacions M'ediques), Universitat Autonoma de Barcelona, Barcelona, Spain.
Steven J. Kittner, Department of Neurology, University of Maryland School of Medicine and Veterans Affairs Maryland Health Care System, Baltimore, MD, United States.
Robin Lemmens, KU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease (LIND), Leuven, Belgium.
Christopher R. Levi, Hunter Medical Research Institute, Newcastle, NSW, Australia.
Caitrin W. McDonough, Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, Gainesville, FL, United States.
James F. Meschia, Department of Neurology, Mayo Clinic, Jacksonville, FL, United States.
Chia-Ling Phuah, Department of Neurology, Washington University School of Medicine & Barnes-Jewish Hospital, St. Louis, MO, United States.
Arndt Rolfs, Centogene AG, Rostock, Germany.
Stefan Ropele, Department of Neurology, Clinical Division of Neurogeriatrics, Medical University Graz, Graz, Austria.

Document Type

Article

Abstract

To personalize the prognostication of post-stroke outcome using MRI-detected cerebrovascular pathology, we sought to investigate the association between the excessive white matter hyperintensity (WMH) burden unaccounted for by the traditional stroke risk profile of individual patients and their long-term functional outcomes after a stroke. We included 890 patients who survived after an acute ischemic stroke from the MRI-Genetics Interface Exploration (MRI-GENIE) study, for whom data on vascular risk factors (VRFs), including age, sex, atrial fibrillation, diabetes mellitus, hypertension, coronary artery disease, smoking, prior stroke history, as well as acute stroke severity, 3- to-6-month modified Rankin Scale score (mRS), WMH, and brain volumes, were available. We defined the unaccounted WMH (uWMH) burden modeling of expected WMH burden based on the VRF profile of each individual patient. The association of uWMH and mRS score was analyzed by linear regression analysis. The odds ratios of patients who achieved full functional independence (mRS < 2) in between trichotomized uWMH burden groups were calculated by pair-wise comparisons. The expected WMH volume was estimated with respect to known VRFs. The uWMH burden was associated with a long-term functional outcome (β = 0.104, < 0.01). Excessive uWMH burden significantly reduced the odds of achieving full functional independence after a stroke compared to the low and average uWMH burden [OR = 0.4, 95% CI: (0.25, 0.63), < 0.01 and OR = 0.61, 95% CI: (0.42, 0.87), < 0.01, respectively]. The excessive amount of uWMH burden unaccounted for by the traditional VRF profile was associated with worse post-stroke functional outcomes. Further studies are needed to evaluate a lifetime brain injury reflected in WMH unrelated to the VRF profile of a patient as an important factor for stroke recovery and a plausible indicator of brain health.

Publication Date

1-1-2021

Publication Title

Frontiers in neurology

ISSN

1664-2295

Volume

12

First Page

700616

PubMed ID

34566844

Digital Object Identifier (DOI)

10.3389/fneur.2021.700616

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