Sex-specific lesion topographies explain outcomes after acute ischemic stroke

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.

Generative lesion pattern decomposition of cognitive impairment after stroke

“… 69–71 Future studies could however choose to add the explicit modelling of white matter effects by quantifying white matter damage within white matter tracts, as was recently done in a lesion-symptom mapping study of acute stroke severity. 72 …”

Generative Lesion Pattern Decomposition of Cognitive Impairment after Stroke

“…[69][70][71] Future studies could however choose to add the explicit modelling of white matter effects by quantifying white matter damage within white matter tracts, as was recently done in a lesion-symptom mapping study of acute stroke severity. 72 Similarly, while beyond the scope of the current work, a promising approach for future research would be to phenotype a large stroke sample, as investigated here, in even greater detail in order to measure fingerprints of small vessel disease, such as white matter hyperintensities, lacunar infarctions, and cerebral atrophy. This avenue will be key given these factors' intricate associations with vascular cognitive impairment.…”