Sex-specific lesion pattern of functional outcomes after stroke

Anna K. Bonkhoff; Martin Bretzner; Sungmin Hong; Markus D. Schirmer; Alexander Cohen; Robert W. Regenhardt; 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; Michael D. Fox; Danilo Bzdok; Ona Wu; Natalia S. Rost

doi:10.1093/braincomms/fcac020

Sex-specific lesion pattern of functional outcomes after stroke

Anna K. Bonkhoff, Martin Bretzner, Sungmin Hong, Markus D. Schirmer, Alexander Cohen, Robert W. Regenhardt, 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. GriessenauerLaura 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, Michael D. Fox, Danilo Bzdok, Ona Wu, Natalia S. Rost

Neurology

Research output: Contribution to journal › Article › peer-review

Abstract

Stroke represents a considerable burden of disease for both men and women. However, a growing body of literature suggests clinically relevant sex differences in the underlying causes, presentations and outcomes of acute ischaemic stroke. In a recent study, we reported sex divergences in lesion topographies: specific to women, acute stroke severity was linked to lesions in the left-hemispheric posterior circulation. We here determined whether these sex-specific brain manifestations also affect long-term outcomes. We relied on 822 acute ischaemic patients [age: 64.7 (15.0) years, 39% women] originating from the multi-centre MRI-GENIE study to model unfavourable outcomes (modified Rankin Scale >2) based on acute neuroimaging data in a Bayesian hierarchical framework. Lesions encompassing bilateral subcortical nuclei and left-lateralized regions in proximity to the insula explained outcomes across men and women (area under the curve = 0.81). A pattern of left-hemispheric posterior circulation brain regions, combining left hippocampus, precuneus, fusiform and lingual gyrus, occipital pole and latero-occipital cortex, showed a substantially higher relevance in explaining functional outcomes in women compared to men [mean difference of Bayesian posterior distributions (men - women) = -0.295 (90% highest posterior density interval = -0.556 to -0.068)]. Once validated in prospective studies, our findings may motivate a sex-specific approach to clinical stroke management and hold the promise of enhancing outcomes on a population level.

Original language	English (US)
Article number	fcac020
Journal	Brain Communications
Volume	4
Issue number	2
DOIs	https://doi.org/10.1093/braincomms/fcac020
State	Published - 2022

Keywords

Acute ischaemic stroke
Bayesian hierarchical modelling
Functional outcomes
Lesion patterns
Sex differences

ASJC Scopus subject areas

Neurology
Psychiatry and Mental health
Biological Psychiatry
Cellular and Molecular Neuroscience

Access to Document

10.1093/braincomms/fcac020

Cite this

Bonkhoff, A. K., Bretzner, M., Hong, S., Schirmer, M. D., Cohen, A., Regenhardt, R. W., Donahue, K. L., Nardin, M. J., Dalca, A. V., Giese, A. K., Etherton, M. R., Hancock, B. L., Mocking, S. J. T., McIntosh, E. C., Attia, J., Benavente, O. R., Bevan, S., Cole, J. W., Donatti, A., ... Rost, N. S. (2022). Sex-specific lesion pattern of functional outcomes after stroke. Brain Communications, 4(2), Article fcac020. https://doi.org/10.1093/braincomms/fcac020

Bonkhoff, AK, Bretzner, M, Hong, S, Schirmer, MD, Cohen, A, Regenhardt, RW, Donahue, KL, Nardin, MJ, Dalca, AV, Giese, AK, Etherton, MR, Hancock, BL, Mocking, SJT, McIntosh, EC, Attia, J, Benavente, OR, Bevan, S, Cole, JW, Donatti, A, Griessenauer, CJ, Heitsch, L, Holmegaard, L, Jood, K, Jimenez-Conde, J, Kittner, SJ, Lemmens, R, Levi, CR, McDonough, CW, Meschia, JF, Phuah, CL, Rolfs, A, Ropele, S, Rosand, J, Roquer, J, Rundek, T, Sacco, RL, Schmidt, R, Sharma, P, Slowik, A, Söderholm, M, Sousa, A, Stanne, TM, Strbian, D, Tatlisumak, T, Thijs, V, Vagal, A, Wasselius, J, Woo, D, Zand, R, McArdle, PF, Worrall, BB, Jern, C, Lindgren, AG, Maguire, J, Fox, MD, Bzdok, D, Wu, O & Rost, NS 2022, 'Sex-specific lesion pattern of functional outcomes after stroke', Brain Communications, vol. 4, no. 2, fcac020. https://doi.org/10.1093/braincomms/fcac020

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title = "Sex-specific lesion pattern of functional outcomes after stroke",

abstract = "Stroke represents a considerable burden of disease for both men and women. However, a growing body of literature suggests clinically relevant sex differences in the underlying causes, presentations and outcomes of acute ischaemic stroke. In a recent study, we reported sex divergences in lesion topographies: specific to women, acute stroke severity was linked to lesions in the left-hemispheric posterior circulation. We here determined whether these sex-specific brain manifestations also affect long-term outcomes. We relied on 822 acute ischaemic patients [age: 64.7 (15.0) years, 39% women] originating from the multi-centre MRI-GENIE study to model unfavourable outcomes (modified Rankin Scale >2) based on acute neuroimaging data in a Bayesian hierarchical framework. Lesions encompassing bilateral subcortical nuclei and left-lateralized regions in proximity to the insula explained outcomes across men and women (area under the curve = 0.81). A pattern of left-hemispheric posterior circulation brain regions, combining left hippocampus, precuneus, fusiform and lingual gyrus, occipital pole and latero-occipital cortex, showed a substantially higher relevance in explaining functional outcomes in women compared to men [mean difference of Bayesian posterior distributions (men - women) = -0.295 (90% highest posterior density interval = -0.556 to -0.068)]. Once validated in prospective studies, our findings may motivate a sex-specific approach to clinical stroke management and hold the promise of enhancing outcomes on a population level.",

keywords = "Acute ischaemic stroke, Bayesian hierarchical modelling, Functional outcomes, Lesion patterns, Sex differences",

author = "Bonkhoff, {Anna K.} and Martin Bretzner and Sungmin Hong and Schirmer, {Markus D.} and Alexander Cohen and Regenhardt, {Robert W.} and Donahue, {Kathleen L.} and Nardin, {Marco J.} and Dalca, {Adrian V.} and Giese, {Anne Katrin} and Etherton, {Mark R.} and Hancock, {Brandon L.} and Mocking, {Steven J.T.} and McIntosh, {Elissa C.} and John Attia and Benavente, {Oscar R.} and Stephen Bevan and Cole, {John W.} and Amanda Donatti and Griessenauer, {Christoph J.} and Laura Heitsch and Lukas Holmegaard and Katarina Jood and Jordi Jimenez-Conde and Kittner, {Steven J.} and Robin Lemmens and Levi, {Christopher R.} and McDonough, {Caitrin W.} and Meschia, {James F.} and Phuah, {Chia Ling} and Arndt Rolfs and Stefan Ropele and Jonathan Rosand and Jaume Roquer and Tatjana Rundek and Sacco, {Ralph L.} and Reinhold Schmidt and Pankaj Sharma and Agnieszka Slowik and Martin S{\"o}derholm and Alessandro Sousa and Stanne, {Tara M.} and Daniel Strbian and Turgut Tatlisumak and Vincent Thijs and Achala Vagal and Johan Wasselius and Daniel Woo and Ramin Zand and McArdle, {Patrick F.} and Worrall, {Bradford B.} and Christina Jern and Lindgren, {Arne G.} and Jane Maguire and Fox, {Michael D.} and Danilo Bzdok and Ona Wu and Rost, {Natalia S.}",

note = "Publisher Copyright: {\textcopyright} 2022 The Author(s). Published by Oxford University Press on behalf of the Guarantors of Brain.",

year = "2022",

doi = "10.1093/braincomms/fcac020",

language = "English (US)",

volume = "4",

journal = "Brain Communications",

issn = "2632-1297",

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T1 - Sex-specific lesion pattern of functional outcomes after stroke

AU - Bonkhoff, Anna K.

AU - Bretzner, Martin

AU - Hong, Sungmin

AU - Schirmer, Markus D.

AU - Cohen, Alexander

AU - Regenhardt, Robert W.

AU - Donahue, Kathleen L.

AU - Nardin, Marco J.

AU - Dalca, Adrian V.

AU - Giese, Anne Katrin

AU - Etherton, Mark R.

AU - Hancock, Brandon L.

AU - Mocking, Steven J.T.

AU - McIntosh, Elissa C.

AU - Attia, John

AU - Benavente, Oscar R.

AU - Bevan, Stephen

AU - Cole, John W.

AU - Donatti, Amanda

AU - Griessenauer, Christoph J.

AU - Heitsch, Laura

AU - Holmegaard, Lukas

AU - Jood, Katarina

AU - Jimenez-Conde, Jordi

AU - Kittner, Steven J.

AU - Lemmens, Robin

AU - Levi, Christopher R.

AU - McDonough, Caitrin W.

AU - Meschia, James F.

AU - Phuah, Chia Ling

AU - Rolfs, Arndt

AU - Ropele, Stefan

AU - Rosand, Jonathan

AU - Roquer, Jaume

AU - Rundek, Tatjana

AU - Sacco, Ralph L.

AU - Schmidt, Reinhold

AU - Sharma, Pankaj

AU - Slowik, Agnieszka

AU - Söderholm, Martin

AU - Sousa, Alessandro

AU - Stanne, Tara M.

AU - Strbian, Daniel

AU - Tatlisumak, Turgut

AU - Thijs, Vincent

AU - Vagal, Achala

AU - Wasselius, Johan

AU - Woo, Daniel

AU - Zand, Ramin

AU - McArdle, Patrick F.

AU - Worrall, Bradford B.

AU - Jern, Christina

AU - Lindgren, Arne G.

AU - Maguire, Jane

AU - Fox, Michael D.

AU - Bzdok, Danilo

AU - Wu, Ona

AU - Rost, Natalia S.

PY - 2022

Y1 - 2022

N2 - Stroke represents a considerable burden of disease for both men and women. However, a growing body of literature suggests clinically relevant sex differences in the underlying causes, presentations and outcomes of acute ischaemic stroke. In a recent study, we reported sex divergences in lesion topographies: specific to women, acute stroke severity was linked to lesions in the left-hemispheric posterior circulation. We here determined whether these sex-specific brain manifestations also affect long-term outcomes. We relied on 822 acute ischaemic patients [age: 64.7 (15.0) years, 39% women] originating from the multi-centre MRI-GENIE study to model unfavourable outcomes (modified Rankin Scale >2) based on acute neuroimaging data in a Bayesian hierarchical framework. Lesions encompassing bilateral subcortical nuclei and left-lateralized regions in proximity to the insula explained outcomes across men and women (area under the curve = 0.81). A pattern of left-hemispheric posterior circulation brain regions, combining left hippocampus, precuneus, fusiform and lingual gyrus, occipital pole and latero-occipital cortex, showed a substantially higher relevance in explaining functional outcomes in women compared to men [mean difference of Bayesian posterior distributions (men - women) = -0.295 (90% highest posterior density interval = -0.556 to -0.068)]. Once validated in prospective studies, our findings may motivate a sex-specific approach to clinical stroke management and hold the promise of enhancing outcomes on a population level.

AB - Stroke represents a considerable burden of disease for both men and women. However, a growing body of literature suggests clinically relevant sex differences in the underlying causes, presentations and outcomes of acute ischaemic stroke. In a recent study, we reported sex divergences in lesion topographies: specific to women, acute stroke severity was linked to lesions in the left-hemispheric posterior circulation. We here determined whether these sex-specific brain manifestations also affect long-term outcomes. We relied on 822 acute ischaemic patients [age: 64.7 (15.0) years, 39% women] originating from the multi-centre MRI-GENIE study to model unfavourable outcomes (modified Rankin Scale >2) based on acute neuroimaging data in a Bayesian hierarchical framework. Lesions encompassing bilateral subcortical nuclei and left-lateralized regions in proximity to the insula explained outcomes across men and women (area under the curve = 0.81). A pattern of left-hemispheric posterior circulation brain regions, combining left hippocampus, precuneus, fusiform and lingual gyrus, occipital pole and latero-occipital cortex, showed a substantially higher relevance in explaining functional outcomes in women compared to men [mean difference of Bayesian posterior distributions (men - women) = -0.295 (90% highest posterior density interval = -0.556 to -0.068)]. Once validated in prospective studies, our findings may motivate a sex-specific approach to clinical stroke management and hold the promise of enhancing outcomes on a population level.

KW - Acute ischaemic stroke

KW - Bayesian hierarchical modelling

KW - Functional outcomes

KW - Lesion patterns

KW - Sex differences

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U2 - 10.1093/braincomms/fcac020

DO - 10.1093/braincomms/fcac020

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VL - 4

JO - Brain Communications

JF - Brain Communications

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ER -

Sex-specific lesion pattern of functional outcomes after stroke

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Keywords

ASJC Scopus subject areas

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