Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.25.308742v1?rss=1 Authors: Bonkhoff, A. K., Schirmer, M. D., Bretzner, M., Hong, S., Regenhardt, R., Brudfors, M., Donahue, K., Nardin, M., Dalca, A., Giese, A.-K., Etherton, M., Hancock, B., Mocking, S., McIntosh, E., Attia, J., Benavente, O., Bevan, S., Cole, J., Donatti, A., Griessenauer, C., Heitsch, L., Holmegaard, L., Jood, K., Jimenez-Conde, J., Kittner, S., Lemmens, R., Levi, C., McDonough, C., Meschia, J., Phuah, C.-L., Rolfs, A., Ropele, S., Rosand, J., Roquer, J., Rundek, T., Sacco, R., Schmidt, R., Sharma, P., Slowik, A., Soderholm, M., Sousa, A., Stanne, T., Strbian, D., Tatlisumak, T., Thijs, V., Vagal, A. Abstract: Acute 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. Copy rights belong to original authors. Visit the link for more info