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Acute Ischemic Stroke Outcomes Linked to Sex-Specific Lesion Patterns

Key findings

  • This study examined whether lesion patterns determined on brain MRI contributed to sex differences in the severity of acute ischemic stroke in 555 patients (38% female)
  • Several similarly configured lesion patterns were linked to more severe strokes in women compared with men, and relevant lesion patterns in women were more widespread
  • The strongest sex differences between lesion pattern effects relevant to stroke severity were noted in the left (posterior) hemisphere
  • These main findings were validated in an independent cohort (n=503, 41% female)
  • The study findings could improve care for both men and women; for example, if the sex differences noted here generalize to cerebral reorganization during recovery, sex-specific rehabilitation protocols may be warranted

The severity of acute ischemic stroke is oftentimes found to be higher in women than men even after accounting for age at onset, comorbidities and pre-stroke level of independence. This is true even though men and women have comparable (normalized) lesion sizes on average.

Neuroimaging has recently been used to map the location of ischemic lesions and link them to specific symptoms after stroke. Now, an international team has done similar research that was sex-specific. The researchers showed that outcome after acute ischemic stroke is associated with sex-specific lesion pattern effects, suggesting stroke care could benefit from being sex-informed.

Anna K. Bonkhoff, MD, neurology research fellow, and Natalia S. Rost, MD, MPH, FAAN, chief of the Stroke Division of the Department of Neurology at Massachusetts General Hospital, served as first and senior authors, respectively, of the report published by the MRI-GENIE and GISCOME investigators and the International Stroke Genetics Consortium in Nature Communications.

Study Methods

The team examined clinical and brain MRI data for 555 patients with acute ischemic stroke, of whom 208 (38%) were female. The main outcome of interest was the National Institutes of Health Stroke Scale (NIHSS) score within the first 48 hours after admission.

On the neuroimages, the researchers specified ten different lesion patterns. They created a Bayesian hierarchical model to estimate how each pattern influenced stroke severity, as judged from the NIHSS score.

Key Results

  • There was no difference between women and men in normalized lesion volume
  • Lesions in motor and language regions of the brain (bilateral subcortical and left-hemispheric inferior frontal, superior and middle temporal regions) explained more severe strokes in both women and men
  • Stroke severity in men was predominantly explained by five lesion patterns; stroke severity in women was linked to similar but more substantial lesion patterns and several additional patterns
  • Lesions in left posterior cerebral artery (PCA)-supplied regions, among other regions (left hippocampus and thalamus; left fusiform, lingual and intracalcarine cortex; left precuneus and cuneal cortex) were associated with disproportionally high stroke severity in women compared with men


Similar main results were obtained when the analyses were repeated in an independent cohort of 503 patients with acute ischemic stroke (41% female).

Toward Sex-Aware Management of Acute Ischemic Stroke

The findings of this study could improve care for both men and women:

  • Future studies of thrombolysis and mechanical thrombectomy should test varying cutoffs for the amount of brain tissue rescued; since lesions of any kind explained greater stroke severity in women, rescuing less tissue in women might be sufficient for positive treatment response
  • If thrombectomy is confirmed to be safe and beneficial for distal PCA occlusion stroke, future thrombectomy studies in this setting should evaluate whether women benefit even more than men
  • It may be especially productive to study whether the sex differences noted here generalize to cerebral reorganization during recovery; if so, sex-specific rehabilitation protocols should be investigated

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