Sex-specific lesion pattern of functional outcomes after stroke.

Anna K BonkhoffMartin BretznerSungmin HongMarkus D SchirmerAlexander Li CohenRobert W RegenhardtKathleen L DonahueMarco J NardinAdrian V DalcaAnne-Katrin GieseMark R EthertonBrandon L HancockSteven J T MockingElissa C McIntoshJohn AttiaOscar R BenaventeStephen BevanJohn W ColeAmanda DonattiChristoph J GriessenauerLaura HeitschLukas HolmegaardKatharina JoodJordi Jimenez-CondeSteven J KittnerRobin LemmensChristopher R LeviCaitrin W McDonoughJames F MeschiaChia-Ling PhuahArndt RolfsStefan RopeleJonathan RosandJaume RoquerTatjana RundekRalph L SaccoReinhold SchmidtPankaj SharmaAgnieszka SlowikMartin SöderholmAlessandro SousaTara M StanneStrbian DanielTurgut TatlisumakVincent ThijsAchala VagalJohan WasseliusDaniel WooRamin ZandPatrick F McArdleBradford B WorrallChristina JernArne G LindgrenJane MaguireMichael D FoxDanilo BzdokOna WuNatalia S Rostnull null
Published in: Brain communications (2022)
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.