Author:
Bonkhoff Anna K.,Schirmer Markus D.,Bretzner Martin,Hong Sungmin,Regenhardt Robert W.,Brudfors Mikael,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,Maguire Jane,Bzdok Danilo,Wu Ona,Rost Natalia S.,
Abstract
AbstractAcute ischemic stroke affects men and women differently in many ways. In particular, women are oftentimes reported to experience a higher acute stroke severity than men. Here, we derived a low-dimensional representation of anatomical stroke lesions and designed a sex-aware Bayesian hierarchical modelling framework for a large-scale, well phenotyped stroke cohort. This framework was tailored to carefully estimate possible sex differences in lesion patterns explaining acute stroke severity (NIHSS) in 1,058 patients (39% female). Anatomical regions known to subserve motor and language functions emerged as relevant regions for both men and women. Female patients, however, presented a more widespread pattern of stroke severity-relevant lesions than male patients. Furthermore, particularly lesions in the posterior circulation of the left hemisphere underlay a higher stroke severity exclusively in women. These sex-sensitive lesion pattern effects could be discovered and subsequently robustly replicated in two large independent, multisite lesion datasets. The constellation of findings has several important conceptual and clinical implications: 1) suggesting sex-specific functional cerebral asymmetries, and 2) motivating a sex-stratified approach to management of acute ischemic stroke. To go beyond sex-averaged stroke research, future studies should explicitly test whether acute therapies administered on the basis of sex-specific cutoff volumes of salvageable tissue will lead to improved outcomes in women after acute ischemic stroke.
Publisher
Cold Spring Harbor Laboratory