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

Anna K. Bonkhoff (), Markus D. Schirmer, Martin Bretzner, Sungmin Hong, Robert W. Regenhardt, Mikael Brudfors, Kathleen L. Donahue, Marco J. Nardin, Adrian V. Dalca, Anne-Katrin Giese, Mark R. Etherton, Brandon L. Hancock, Steven J. T. Mocking, Elissa C. McIntosh, John Attia, Oscar R. Benavente, Stephen Bevan, 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, 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, Martin Söderholm, Alessandro Sousa, Tara M. Stanne, Daniel Strbian, Turgut Tatlisumak, Vincent Thijs, Achala Vagal, Johan Wasselius, Daniel Woo, Ramin Zand, Patrick F. McArdle, Bradford B. Worrall, Christina Jern, Arne G. Lindgren, Jane Maguire, Danilo Bzdok, Ona Wu and Natalia S. Rost
Additional contact information
Anna K. Bonkhoff: J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Harvard Medical School
Markus D. Schirmer: J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Harvard Medical School
Martin Bretzner: J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Harvard Medical School
Sungmin Hong: J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Harvard Medical School
Robert W. Regenhardt: J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Harvard Medical School
Mikael Brudfors: School of Biomedical Engineering & Imaging Sciences, King’s College London
Kathleen L. Donahue: J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Harvard Medical School
Marco J. Nardin: J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Harvard Medical School
Adrian V. Dalca: Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology
Anne-Katrin Giese: University Medical Center Hamburg‐Eppendorf
Mark R. Etherton: J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Harvard Medical School
Brandon L. Hancock: Massachusetts General Hospital
Steven J. T. Mocking: Massachusetts General Hospital
Elissa C. McIntosh: Massachusetts General Hospital
John Attia: Hunter Medical Research Institute
Oscar R. Benavente: University of British Columbia
Stephen Bevan: School of Life Sciences, University of Lincoln
John W. Cole: University of Maryland School of Medicine and Veterans Affairs Maryland Health Care System
Amanda Donatti: School of Medical Sciences, University of Campinas (UNICAMP) and the Brazilian Institute of Neuroscience and Neurotechnology (BRAINN)
Christoph J. Griessenauer: Geisinger
Laura Heitsch: Washington University School of Medicine
Lukas Holmegaard: University of Gothenburg
Katarina Jood: University of Gothenburg
Jordi Jimenez-Conde: Universitat Autonoma de Barcelona
Steven J. Kittner: University of Maryland School of Medicine and Veterans Affairs Maryland Health Care System
Robin Lemmens: Experimental Neurology and Leuven Research Institute for Neuroscience and Disease (LIND)
Christopher R. Levi: University of Newcastle
Caitrin W. McDonough: University of Florida
James F. Meschia: Mayo Clinic
Chia-Ling Phuah: Washington University School of Medicine & Barnes-Jewish Hospital
Arndt Rolfs: Centogene AG
Stefan Ropele: Medical University Graz
Jonathan Rosand: J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Harvard Medical School
Jaume Roquer: Universitat Autonoma de Barcelona
Tatjana Rundek: University of Miami
Ralph L. Sacco: University of Miami
Reinhold Schmidt: Medical University Graz
Pankaj Sharma: Institute of Cardiovascular Research, Royal Holloway University of London (ICR2UL)
Agnieszka Slowik: Jagiellonian University Medical College
Martin Söderholm: Lund University
Alessandro Sousa: School of Medical Sciences, University of Campinas (UNICAMP) and the Brazilian Institute of Neuroscience and Neurotechnology (BRAINN)
Tara M. Stanne: the Sahlgrenska Academy at University of Gothenburg
Daniel Strbian: Helsinki University Hospital and University of Helsinki
Turgut Tatlisumak: Sahlgrenska Academy at University of Gothenburg
Vincent Thijs: Florey Institute of Neuroscience and Mental Health
Achala Vagal: University of Cincinnati College of Medicine
Johan Wasselius: Lund University
Daniel Woo: University of Cincinnati College of Medicine
Ramin Zand: Geisinger
Patrick F. McArdle: University of Maryland School of Medicine
Bradford B. Worrall: University of Virginia
Christina Jern: the Sahlgrenska Academy at University of Gothenburg
Arne G. Lindgren: Skåne University Hospital
Jane Maguire: University of Technology Sydney
Danilo Bzdok: McGill University
Ona Wu: Massachusetts General Hospital
Natalia S. Rost: J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Harvard Medical School

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-23492-3

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