Biological Mechanism of Sex Difference in Stroke Manifestation and Outcomes
Wi‐Sun Ryu, Jinyong Chung, Dawid Schellingerhout, Sang‐Wuk Jeong, Hang‐Rai Kim, Jung E. Park, Beom Joon Kim, Joon‐Tae Kim, Keun‐Sik Hong, Kyung‐Bok Lee, Tai Hwan Park, Sang‐Soon Park, Jong‐Moo Park, Kyusik Kang, Yong‐Jin Cho, Hong‐Kyun Park, Byung‐Chul Lee, Kyung‐Ho Yu, Mi Sun Oh, Soo Joo Lee, Jae Guk Kim, Jae‐Kwan Cha, Dae‐Hyun Kim, Jun Lee, Moon‐Ku Han, Man‐Seok Park, Kang‐Ho Choi, Juneyoung Lee, Hee‐Joon Bae, Dong‐Eog Kim
Abstract
<h3>Background and Objectives</h3> Female patients tend to have greater disability and worse long-term outcomes after stroke than male patients. To date, the biological basis of sex difference in ischemic stroke remains unclear. We aimed to 1) assess sex differences in clinical manifestation and outcomes of acute ischemic stroke and 2) investigate whether the sex disparity is due to different infarct locations or different impacts of infarct in the same location. <h3>Methods</h3> This MRI-based multicenter study included 6,464 consecutive patients with acute ischemic stroke (<7-days) from 11-centers in South-Korea (May-2011∼January-2013). Multivariable statistical and brain mapping methods were used to analyze clinical and imaging data collected prospectively: admission National Institutes of Health Stroke Scale (NIHSS)-score, early neurological deterioration within 3-weeks, modified Rankin Scale (mRS)-score at 3-months, and culprit cerebrovascular lesion (symptomatic large artery steno-occlusion and cerebral infarction) locations. <h3>Results</h3> Mean (SD) age was 67.5 (12.6) years, and 2,641 (40.9%) were female patients. Percentage infarct volumes on diffusion-weighted MRI did not differ between female patients and male patients (median 0.14% vs. 0.14%, P=0.35). However, female patients showed higher stroke severity (NIHSS-score, median 4 vs. 3, P<0.001) and had more frequent early neurological deterioration (adjusted-difference 3.5%; P=0.002) than male patients. Female patients had more frequent striatocapsular lesions (43.6% vs. 39.8%, P=0.001) and less frequent cerebrocortical and cerebellar lesions than male patients, which aligned with angiographic findings: female patients had more prevalent symptomatic steno-occlusion of the middle cerebral artery (31.1% vs. 25.3%; P<0.001) compared to male patients, who had more frequent symptomatic steno-occlusion of the extracranial internal carotid artery (14.2% vs. 9.3%; P<0.001) and vertebral artery (6.5% vs. 4.7%; P=0.001). Cortical infarcts in female patients, specifically left-sided parieto-occipital regions, were associated with higher NIHSS-scores than expected for similar infarct volumes in male patients. Consequently, female patients had a higher likelihood of unfavorable functional outcome (mRS-score>2) than male patients (adjusted-absolute-difference 4.5%; 95%-CI 2.0–7.0; P<0.001). <h3>Discussion</h3> Female patients have more frequent middle cerebral artery disease and striatocapsular motor-pathway involvement with acute ischemic stroke, along with left parieto-occipital cortical infarcts showing greater severity for equivalent infarct volumes than in male patients. This leads to more severe initial neurological symptoms, higher susceptibility to neurological worsening, and less 3-month functional independence, when compared with male patients.