There are several controversies regarding the role of sex and gender in the pathophysiology and management of acute stroke. Assessing the role of sex, i.e., biological/pathophysiological factors, and gender, i.e., sociocultural factors, in isolation is often not possible since they are closely intertwined with each other. To complicate matters even more, the functional baseline status of women and men at the time of their first stroke is substantially different, whereby women have, on average, a poorer reported/ascertained baseline function compared to men. These differences in baseline variables account for a large part of the differences in post-stroke outcomes between women and men. Adjusting for these baseline differences is difficult, and in many cases, residual confounding cannot be excluded. Despite these obstacles, a better understanding of how patient sex and gender differences influence acute stroke and stroke care pathways is crucial to avoid biases and allow us to provide the best possible care for all acute stroke patients. Disregarding patient sex and gender on one hand and ignoring potential confounding factors in sex- and gender-stratified analyses on the other hand, may cause researchers to come to erroneous conclusions and physicians to provide suboptimal care. This review outlines sex- and gender-related factors in key aspects of acute stroke, including acute stroke epidemiology, diagnosis, access to care, treatment outcomes, and post-acute care. We also attempt to outline knowledge gaps, which deserve to be studied in further detail, and practical implications for physicians treating acute stroke patients in their daily practice.

Thrombolysis for acute ischemic stroke has predominantly been with alteplase for over a quarter of a century. In recent years, with trials showing evidence of higher rates of successful reperfusion, similar safety profile and efficacy of tenecteplase (TNK) as compared to alteplase, TNK has now emerged as another potential choice for thrombolysis in acute ischemic stroke. In this review, we will focus on these recent advances, aiming: (1) to provide a brief overview of thrombolysis in stroke; (2) to provide comparisons between alteplase and TNK for clinical, imaging, and safety outcomes; (3) to focus on key subgroups of interest to understand if there is an advantage of using TNK over alteplase or vice-versa, to review available evidence on role of TNK in intra-arterial thrombolysis, as bridging therapy and in mobile stroke units; and (4) to summarize what to expect in the near future from recently completed trials and propose areas for future research on this evolving topic. We present compelling data from several trials regarding the safety and efficacy of TNK in acute ischemic stroke along with completed yet unpublished trials that will help provide insight into these unanswered questions.

Background: and Purpose Infarct volume and other imaging markers are increasingly used as surrogate measures for clinical outcome in acute ischemic stroke research, but how improvements in these imaging surrogates translate into better clinical outcomes is currently unclear. We investigated how changes in infarct volume at 24 hours alter the probability of achieving good clinical outcome (modified Rankin Scale [mRS] 0–2). Methods: Data are from endovascular thrombectomy patients from the randomized controlled ESCAPE-NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischaemic Stroke) trial. Infarct volume at 24 hours was manually segmented on non-contrast computed tomography or diffusion-weighted magnetic resonance imaging. Probabilities of achieving good outcome based on infarct volume were obtained from a multivariable logistic regression model. The probability of good outcome was plotted against infarct volume using linear spline regression. Results: A total of 1,099 patients were included in the analysis (median final infarct volume 24.9 mL [interquartile range: 6.6–92.2]). The relationship between total infarct volume and good outcome probability was nearly linear for infarct volumes between 0 mL and 250 mL. In this range, a 10% increase in the probability of achieving mRS 0–2 required a decrease in infarct volume of approximately 34.0 mL (95% confidence interval: -32.5 to -35.6). At infarct volumes above 250 mL, the probability of achieving mRS 0–2 probability was near zero. The relationships of tissue-specific infarct volumes and parenchymal hemorrhage volume generally showed similar patterns, although variability was high. Conclusion There seems to be a near-linear association between total infarct volume and probability of achieving good outcome for infarcts up to 250 mL, whereas patients with infarct volumes greater than 250 mL are highly unlikely to have a favorable outcome.