Sex-specific lesion topographies explain outcomesafter acute ischemic stroke

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.

doi:10.1101/2020.09.25.308742

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bioRxiv · 10.1101/2020.09.25.308742

Sex-specific lesion topographies explain outcomesafter acute ischemic stroke

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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.

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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.. 2020-09-27. Sex-specific lesion topographies explain outcomesafter acute ischemic stroke. https://doi.org/10.1101/2020.09.25.308742

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