Sex and Hemisphere - A Neglected, Nature-Determined Relationship in Acute Ischemic Stroke

Sex differences in the structural connectome of the brain are clinically highly relevant, but they have mostly been neglected in stroke trials. We investigated the impact of the interaction sex-by-hemisphere on outcome in stroke patients after intravenous thrombolysis (IVT).

This is an observational study based on consecutively collected supratentorial stroke patients treated with IVT (n = 1,231). The 3-month modified Rankin scale (mRS) was estimated by adjusted binary (mRS 0-2 for good outcome) and ordinal regression analysis. As baseline characteristics differ substantially between the sexes, we aimed for better covariate balance by employing coarsened exact matching.

Sex-by-hemisphere predicted good outcome in the entire cohort (726 left, 505 right hemispheric strokes, p valueinteraction 0.032) and in the matched cohort (338 left, 273 right, p valueinteraction 0.003). Ordinal regression suggested a comparable estimate in the matched cohort (p valueinteraction 0.006). Further investigation revealed relevant between-sex and within-sex risk: right hemispheric strokes in men were 1.54 times (95% confidence intervals (CIs) 1.15-2.01) more likely than in women to achieve mRS 0-2. Women with right hemispheric strokes were 0.72 times (95% CI 0.54-0.92) less likely to reach mRS 0-2 than women with left hemispheric strokes. Conversely, men with right hemispheric strokes were 1.35 times (95% CI 1.06-1.70) more likely to achieve mRS 0-2 than men with left hemispheric strokes.

This study suggests that outcomes are different in both sexes after IVT when different hemispheres are affected. Further consideration of this hypothesis in clinical trials might help in guiding individualized, injury-specific treatment approaches for acute ischemic stroke.