Outcome after acute ischemic stroke is linked to sex-specific lesion patterns

Anna K. Bonkhoff, J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. abonkhoff@mgh.harvard.edu.
Markus D. Schirmer, J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Martin Bretzner, J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Sungmin Hong, J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Robert W. Regenhardt, J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Mikael Brudfors, School of Biomedical Engineering & Imaging Sciences, King's College London, London, UK.
Kathleen L. Donahue, J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Marco J. Nardin, J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Adrian V. Dalca, Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, Boston, MA, USA.
Anne-Katrin Giese, Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Mark R. Etherton, J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Brandon L. Hancock, Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA.
Steven J. Mocking, Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA.
Elissa C. McIntosh, Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA.
John Attia, Hunter Medical Research Institute, Newcastle, NSW, Australia.
Oscar R. Benavente, Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, BC, Canada.
Stephen Bevan, School of Life Sciences, University of Lincoln, Lincoln, UK.
John W. Cole, Department of Neurology, University of Maryland School of Medicine and Veterans Affairs Maryland Health Care System, Baltimore, MD, USA.
Amanda Donatti, School of Medical Sciences, University of Campinas (UNICAMP) and the Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, Sao Paulo, Brazil.
Christoph J. Griessenauer, Department of Neurosurgery, Geisinger, Danville, PA, USA.
Laura Heitsch, Department of Emergency Medicine, Washington University School of Medicine, St Louis, MO, USA.
Lukas Holmegaard, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Katarina Jood, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Jordi Jimenez-Conde, Department of Neurology, Neurovascular Research Group (NEUVAS), IMIM-Hospital del Mar (Institut Hospital del Mar d'Investigacions Mèdiques), 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, USA.
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, School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia.
Caitrin W. McDonough, Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, Gainesville, FL, USA.
James F. Meschia, Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
Chia-Ling Phuah, Department of Neurology, Washington University School of Medicine & Barnes-Jewish Hospital, St Louis, MO, USA.
Arndt Rolfs, Centogene AG, Rostock, Germany.

Document Type

Article

Abstract

Acute ischemic stroke affects men and women differently. In particular, women are often reported to experience higher acute stroke severity than men. We derived a low-dimensional representation of anatomical stroke lesions and designed a Bayesian hierarchical modeling framework tailored to estimate possible sex differences in lesion patterns linked to acute stroke severity (National Institute of Health Stroke Scale). This framework was developed in 555 patients (38% female). Findings were validated in an independent cohort (n = 503, 41% female). Here, we show brain lesions in regions subserving motor and language functions help explain stroke severity in both men and women, however more widespread lesion patterns are relevant in female patients. Higher stroke severity in women, but not men, is associated with left hemisphere lesions in the vicinity of the posterior circulation. Our results suggest there are sex-specific functional cerebral asymmetries that may be important for future investigations of sex-stratified approaches to management of acute ischemic stroke.

Medical Subject Headings

Aged; Aged, 80 and over; Bayes Theorem; Brain Mapping; Brain Stem (blood supply, diagnostic imaging, pathology); Cerebral Revascularization (methods); Cohort Studies; Female; Humans; Image Processing, Computer-Assisted; Ischemic Stroke (diagnostic imaging, pathology, therapy); Magnetic Resonance Imaging; Male; Middle Aged; Risk Factors; Sensorimotor Cortex (blood supply, diagnostic imaging, pathology); Severity of Illness Index; Sex Factors; Thalamus (blood supply, diagnostic imaging, pathology); Treatment Outcome

Publication Date

6-2-2021

Publication Title

Nature communications

E-ISSN

2041-1723

Volume

12

Issue

1

First Page

3289

PubMed ID

34078897

Digital Object Identifier (DOI)

10.1038/s41467-021-23492-3

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