Sex-specific lesion pattern of functional outcomes after stroke
Authors: Bonkhoff Anna K. , Bretzner Martin , Hong Sungmin , Schirmer Markus D. , Cohen Alexander , Regenhardt Robert W. , Donahue Kathleen L. , Nardin Marco J. , Dalca Adrian V. , Giese Anne-Katrin , Etherton Mark R. , Hancock Brandon L. , Mocking Steven J. T. , McIntosh Elissa C. , Attia John , Benavente Oscar R. , Bevan Stephen , Cole John W. , Donatti Amanda , Griessenauer Christoph J. , Heitsch Laura , Holmegaard Lukas , Jood Katarina , Jimenez-Conde Jordi , Kittner Steven J. , Lemmens Robin , Levi Christopher R. , McDonough Caitrin W. , Meschia James F. , Phuah Chia-Ling , Rolfs Arndt , Ropele Stefan , Rosand Jonathan , Roquer Jaume , Rundek Tatjana , Sacco Ralph L. , Schmidt Reinhold , Sharma Pankaj , Slowik Agnieszka , Söderholm Martin , Sousa Alessandro , Stanne Tara M. , Strbian Daniel , Tatlisumak Turgut , Thijs Vincent , Vagal Achala , Wasselius Johan , Woo Daniel , Zand Ramin , McArdle Patrick F. , Worrall Bradford B. , Jern Christina , Lindgren Arne G. , Maguire Jane , Fox Michael D. , Bzdok Danilo , Wu Ona , Rost Natalia S. ,   MRI-GENIE and GISCOME Investigators and the International Stroke Genetics Consortium, Bonkhoff Anna K. , Bretzner Martin , Hong Sungmin , Schirmer Markus D. , Cohen Alexander , Regenhardt Robert W. , Donahue Kathleen L. , Nardin Marco J. , Dalca Adrian V. , Giese Anne-Katrin , Etherton Mark R. , Hancock Brandon L. , Mocking Steven J. T. , McIntosh Elissa C. , Attia John , Benavente Oscar R. , Bevan Stephen , Cole John W. , Donatti Amanda , Griessenauer Christoph J. , Heitsch Laura , Holmegaard Lukas , Jood Katarina , Jimenez-Conde Jordi , Kittner Steven J. , Lemmens Robin , Levi Christopher R. , McDonough Caitrin W. , Meschia James F. , Phuah Chia-Ling , Rolfs Arndt , Ropele Stefan , Rosand Jonathan , Roquer Jaume , Rundek Tatjana , Sacco Ralph L. , Schmidt Reinhold , Sharma Pankaj , Slowik Agnieszka , Söderholm Martin , Sousa Alessandro , Stanne Tara M. , Strbian Daniel , Tatlisumak Turgut , Thijs Vincent , Vagal Achala , Wasselius Johan , Woo Daniel , Zand Ramin , McArdle Patrick F. , Worrall Bradford B. , Jern Christina , Lindgren Arne G. , Maguire Jane , Fox Michael D. , Bzdok Danilo , Wu Ona , Rost Natalia S. 
Published: January 2022

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 &gt;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.