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Ischemic Stroke Imaging and Outcomes: Differences between Sexes1Department of Neurology, Dell Medical School at University of Texas, Austin, Austin, TX, United States
Synopsis
Stroke is a treatable disease and neuroimaging can identify salvageable tissue, directly impacting treatment decisions. Women experience stroke differently than men with higher severity, worse outcomes, and varying therapeutic response. We examined the contribution of sex and age to stroke outcome with emphasis on therapeutic targets on MRI. MR images were evaluated for predictive imaging factors. A 90-day mRS was obtained to assess functional independence. Women present more often with treatable ischemic stroke than men as defined by MR imaging factors. Sex modulates the age-dependent stroke outcome but upon stratification for treatment, difference in outcome favoring men was not observed.
Introduction
Stroke is a treatable disease in which neuroimaging can objectively identify properties of salvageable tissue therefore directly impacting treatment decisions. Women experience stroke differently than men with higher severity, worse outcomes, and varying responses to therapies.1, 2 The factors shown to predict clinical severity, clinical outcome, and/or clinical response to acute recanalization therapy include: 1. The ischemic volume of the acutely hypoperfused brain tissue determined by perfusion weighted imaging (PWI); 2. The core volume of irreversibly injured brain within the ischemic region determined by diffusion weighted imaging (DWI); 3. Penumbra volume as the difference in volume of the ischemic and core regions indicating the at-risk but salvageable brain (the ischemic penumbra); 4. Occluded artery that is responsible for the ischemia. These factors predict stroke outcomes such as functional independence as measured by the modified Rankin Scale (mRS) and importantly, they are measurable by clinical magnetic resonance imaging. These imaging factors have not been explored as the basis for sex difference in stroke presentation and outcomes.
Studies indicate age is a confounder and potential mediator of sex differences seen with treatment mitigating sex differences. We have examined the contribution of sex and age to outcome of ischemic stroke with particular emphasis on therapeutic targets on MRI. We hypothesize that sex and age influence target presentation and outcome with women having a greater treatment effect.
Methods
Consecutive ischemic stroke patients presenting within 24 hours of time from last known well (TLKW) were included in the Lesion Evolution in Stroke and Ischemia On Neuroimaging (LESION) Study. The LESION population had a baseline admit National Institutes of Health Stroke Scale (NIHSS) score ≥ 4, an evaluable baseline MRI scan done within 24 hours since TLKW and obtained before any acute intervention. MR images were evaluated for the following predictive factors: ischemic region volume, ischemic core volume, ischemic penumbra volume, and occluded artery. A 90-day mRS was obtained on a subset of the LESION population. Analysis focused on potential for therapy i.e. location of arterial occlusion, the ischemic region, or ischemic penumbra. Imaging-defined therapeutic targets and their effect on outcome were examined for women and men through stratification and adjustment.Results
The LESION study included 1,092 patients and the subset with a recorded 90-day mRS was comprised of 166 patients. The probability of imaging target detection was significantly different between men and women (Fig. 1A), with women more likely to present with all assessed imaging targets, odds ratios between 1.36 – 1.59, p<0.02, adjusted for NIHSS, age, and TLKW to MRI scan. This trend held for the entire 24-hours studied. Multivariate analysis of 90-day mRS found a sex*age interaction when adjusting for stroke severity (admit NIHSS), age, and location of occlusion, indicating that for women only, the average 90-day mRS increases by 1 point for every additional 20 years of onset age (Fig. 1B). Stratification by any treatment (yes/no) eliminated these sex and sex*age effects.Conclusions
Women present more often with treatable ischemic stroke than men as defined by MR imaging factors. The greater probability of potentially viable and/or treatable imaging targets in women at all time points suggests that tissue injury is slower to evolve in women. Sex modulates the age-dependent stroke outcome but upon stratification for treatment, difference in outcome favoring men was not observed. Identification of differences in imaging targets as well as age*sex interaction is a step toward further refining imaging selection of patients for acute reperfusion therapy and trials indicating the power of MRI in the standard of care for this pathology.Acknowledgements
The LESION database was created and funded by the Division of Intramural Research of the National Institutes of Health, National Institute of Neurological Disorders and Stroke. This analysis and publication were also made possible by funding made available by the Texas Legislature to the Lone Star Stroke Clinical Trial Network. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the Government of the United States or the State of Texas.References
1. Reeves MJ, Bushnell CD, Howard G, Gargano JW, Duncan PW, Lynch G, Khatiwoda A, Lisabeth L. Sex differences in stroke: epidemiology, clinical presentation, medical care, and outcomes. The Lancet Neurology 2008;7(10):915-926.
2. Faber JE, Moore SM, Lucitti JL, Aghajanian A, Zhang H. Sex Differences in the Cerebral Collateral Circulation. Transl Stroke Res 2017;8(3):273-283.
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