Johanna Maria Ospel

BACKGROUND: Restoring blood flow to ischemic tissue is the cornerstone of acute stroke therapy and is usually beneficial. However, when reperfusion is achieved for severely injured tissue, it is often futile and may occasionally cause harm. We aim to determine the prevalence and variables associated with clinical no improvement or acute worsening at 24 hours despite reperfusion in patients with large-vessel occlusion stroke treated with endovascular thrombectomy. METHODS: Data are from ESCAPE-NA1 (Safety and Efficacy of Nerinetide [NA-1] in Subjects Undergoing Endovascular Thrombectomy for Stroke), a randomized trial of nerinetide in patients with acute large-vessel occlusion stroke undergoing endovascular thrombectomy. Patients with unsuccessful recanalization (expanded Thrombolysis in Cerebral Infarction <2b), infarcts in new vascular territories, vessel perforation, or remote parenchymal hemorrhage were excluded. Clinical outcomes after reperfusion were classified by 24-hour National Institutes of Health Stroke Scale changes compared with baseline: improvement (≥4-point improvement), no improvement (±3-point from baseline), and worsening (≥4-point worsening). Baseline variables associated with worsening were identified using logistic regression. In the computed tomography perfusion subgroup, prevalence of parenchymal hemorrhage (any parenchymal hematoma) and infarct progression (final infarct volume exceeding the initial hypoperfused region) were evaluated. RESULTS: A total of 833 patients were included (median age, 70.9 years [interquartile range, 60.7–79.4]; 51.4% men). After reperfusion, 669 (80.3%) patients improved, 135 (16.2%) showed no improvement, and 29 (3.5%) worsened. Independent predictors of worsening were longer onset-to-reperfusion time (adjusted odds ratio, 1.02 [95% CI, 1.00–1.04] per 10-minute increase) and greater degree of sedation (adjusted odds ratio, 1.78 [95% CI, 1.29–2.46] per category of none, conscious sedation, and general anesthesia). In the computed tomography perfusion subgroup (n=414), among patients with worsening after reperfusion, parenchymal hemorrhage was seen in 5 patients (31.3%) and infarct progression in 4 patients (25%). CONCLUSIONS: Clinical worsening in the acute period (ie, early neurological deterioration) despite reperfusion and the absence of procedure-related complications was rare in this selected large-vessel occlusion stroke cohort (3.5%). Factors associated with worsening after reperfusion were a longer time from symptom onset-to-reperfusion and a higher degree of sedation.

Artificial intelligence is increasingly integrated into acute stroke management, demonstrating strong performance in tasks such as large vessel occlusion detection, Alberta Stroke Program Early Computed Tomography Score scoring, and functional outcome prediction. However, concerns persist regarding both the black-box nature of these models and algorithmic bias that may exacerbate disparities in stroke incidence, treatment, and outcomes across racial and socioeconomic subgroups. This review synthesizes the current literature on explainable artificial intelligence and fairness in artificial intelligence applications for acute stroke management, identifies persistent challenges, and outlines recommendations for the development of equitable and trustworthy systems in stroke care. Recent studies have increasingly adopted post hoc explainability methods, though these are limited by approximation and misleading interpretations, especially since explanations are rarely formally tested. Explainability and fairness remain largely disconnected, with fairness evaluation remaining uncommon due to limited demographic metadata, regulatory constraints, and the absence of stroke-specific fairness criteria. Generalizability also remains a concern due to suboptimal data set partitioning strategies and inadequate reporting practices. Responsible artificial intelligence for acute stroke management requires unified evaluation frameworks that jointly assess explainability, fairness, and generalizability.

Purpose: Neurointerventional procedures, which are resource-intensive and generate significant waste, remain a major environmental challenge. This international survey aimed to explore the awareness, practices, and barriers surrounding sustainability in neurointervention. Methods: A cross-sectional online survey was conducted among neurointerventional specialists using a convenience sampling approach. The questionnaire focused on sustainability awareness, surgical gown preferences, workplace sustainability initiatives, perceived barriers, and support for sustainability measures. Results: One-hundred-thirty-eight respondents completed the survey between October 15th, 2025 and December 15th, 2025 (107 [77.5%] male, with a background in neuroradiology [88/138, 63.8%], neurology [32/138, 23.2%], and neurosurgery [16/138, 11.6%]). Results revealed a gap between personal and professional sustainability actions, with respondents engaging more in sustainable practices in private life than at work. While 78.7% prioritized sustainability privately, only 71.7% did so professionally. Key barriers to implementing sustainability included “limited alternatives”, “lack of awareness”, and “inadequate financial incentives”. However, there was strong support for sustainability initiatives, especially in areas such as sustainable procurement and events organized by professional societies. Notably, despite a preference for reusable surgical gowns (75.9%), disposable gowns dominated current practice (76.7%). Conclusion: This study suggests a gap between neurointerventional specialists’ personal sustainability preferences and professional practices, which may be influenced by systemic barriers. While respondents generally expressed support for sustainable initiatives, broader adoption likely requires structural changes at institutional and policy levels.

Background: Infarct evolution on diffusion‐weighted imaging (DWI) after complete recanalization and its relationships to computed tomography perfusion core and outcome remain uncertain. Methods: From a multicenter registry (2014–2024), we identified 189 patients with anterior‐circulation large‐vessel occlusion, modified Thrombolysis in Cerebral Infarction grade 3 recanalization, prethrombectomy computed tomography perfusion, immediate DWI within 24 hours, and delayed DWI at 24 to 168 hours. Robust linear regression identified predictors of DWI volume change; logistic regression assessed 90‐day modified Rankin Scale scores of 0 to 2. Results: DWI volume increased in 162 of 189 patients (85.7%), from a median of 4.8 mL (interquartile range, 1.1–16.4) immediately after thrombectomy to 11.7 mL (interquartile range, 3.8–40.2) on delayed imaging; the median change was 4.4 mL (interquartile range, 0.7–14.8). Baseline computed tomography perfusion core was method‐sensitively associated with greater change in the full model without immediate DWI (β=0.154 [heteroscedasticity‐consistent 95% CI, −0.024 to 0.332]; P =0.09; bootstrap 95% CI, 0.018–0.336; P =0.014) and attenuated after immediate DWI adjustment (β=0.100; P =0.22; bootstrap P =0.077). Each decile increase in volume change was associated with lower odds of functional independence (adjusted odds ratio, 0.81 [95% CI, 0.68–0.97]; P =0.021). Delayed DWI showed the best outcome discrimination. Conclusions: DWI‐defined infarct volume increased after complete recanalization and was associated with functional outcome. The core association was method‐sensitive and attenuated after accounting for immediate DWI, supporting a possible mediated rather than independent pathway.

Endovascular thrombectomy for medium-vessel occlusion (MeVO) stroke has emerged as a major area of clinical and research uncertainty. Unlike large-vessel occlusions, MeVO stroke encompasses substantial heterogeneity in neurological severity, occlusion location, and vessel caliber, complicating both bedside decision-making and trial design. Recent randomized trials of endovascular thrombectomy for MeVO stroke have produced heterogeneous and sometimes conflicting results, leaving clinicians uncertain about patient selection and equipoise. In this review, we examine how differences in occlusion location, vessel size, and baseline National Institutes of Health Stroke Scale across recent MeVO trials may influence observed treatment effects, safety signals, and interpretation of trial results. We review how procedural risk varies across anatomic and clinical phenotypes and summarize subgroup findings that highlight important limitations of treating MeVO stroke as a uniform entity. We then propose a pragmatic, anatomy- and severity-informed framework to guide clinical decision-making and trial design, delineating scenarios where endovascular thrombectomy is beneficial, those where harm likely outweighs benefit, and a broad intermediate group requiring individualized approaches. Lastly, we discuss implications for future trials, including the need for explicit stratification, reconsideration of outcome measures, and exploration of alternative reperfusion strategies in select MeVO populations.

Stroke triggers a multifaceted and dynamic immune response, engaging both innate and adaptive mechanisms that evolve in distinct spatial patterns. While these processes contribute to tissue repair and debris clearance, they also drive secondary injury, shape long-term recovery, and predispose patients to life-threatening complications such as infections and recurrent vascular events. Importantly, preexisting systemic inflammation and immune alterations may interact with the poststroke immune cascade, amplifying risk for complicating outcomes. Despite recent advances, the translation of immunomodulatory therapies remains limited, highlighting the need for a better understanding of immune mechanisms in human stroke. Blood-based biomarkers, including cytokines, chemokines, alarmins, and immune cell profiles, have not only emerged as promising tools to monitor the poststroke immune response but also as potential therapeutic targets. At the same time, advanced neuroimaging techniques are opening new avenues to visualize blood-brain barrier breakdown, microglial activation, and other hallmarks of cerebral inflammation. Together, these circulating and imaging biomarkers offer complementary insights into the evolving brain-immune crosstalk after stroke. This review synthesizes current concepts of poststroke immune responses, systemic interactions, and the role of established and emerging blood-based and imaging biomarkers. We highlight the translational potential of integrative biomarker strategies to improve individualized prognosis, guide precision therapies, and ultimately bridge the gap between mechanistic discovery and clinical application.

During acute ischemic stroke, cerebral tissue undergoes different stages of ischemic damage and evolves towards irreversible injury at a varying pace depending on local perfusion and metabolic factors. This complex ischemic pathological process represents a dynamic continuum that has been historically conceptualized as a binary ischemic core-penumbra model. Although this simplification has proven useful for explaining the evolution of tissue damage in acute stroke, important nuances with clinical implications might be underappreciated. In this review, we critically appraise the pathophysiology and conventional clinical concepts adopted to explain infarct evolution in the early phases of ischemic stroke. We discuss recent mounting evidence that challenges the traditional compartmentalization of the ischemic core, penumbra, and oligemia, calling for more nuanced pathophysiological tissue concepts. For example, clinical benefits and the harmful hemorrhagic transformation associated with reperfusion therapies are observed across a spectrum of core volumes, challenging the deterministic assumptions of the core-penumbra hypothesis. Automated image processing systems reinforce this simplification of stroke pathophysiology, leading to misinterpretation of the range of truth in human imaging. We propose a modified definition of the core-penumbra-oligemia continuum that includes 6 levels of ischemic progression and their corresponding clinical implications: (1) benign oligemia, (2) vulnerable oligemia, (3) durable penumbra, (4) critical penumbra, (5) nonleaky core, and (6) leaky core. This more granular classification could better reflect the continuum of pathological ischemic changes and vulnerability. The proposed 6 levels can provide a framework for future neuroimaging efforts to better understand tissue fate and infarct evolution in ischemic stroke, ultimately informing treatment decision-making and refining targeting for new therapeutic approaches.

Background: As endovascular thrombectomy has become the standard of care for patients with large-vessel occlusion stroke, interest in intra-arterial (IA) selective brain cooling as a method of delivering therapeutic hypothermia has emerged. However, the impact of catheter configuration and competing warm blood flow on IA cooling efficiency is not well understood. Methods: We constructed a closed-loop circulatory system to perform in vitro experiments of IA cooling and tested the impact of seven catheter configurations on cooling efficiency, including single and co-axial catheter setups, non-insulated and insulated catheters, and proximal blood flow control (using balloon guide catheter (BGC) inflation) versus no flow control. Thermal modeling was performed to assess the relationship between catheter and internal carotid artery (ICA) flow rates and predicted brain temperature. Results: After 10 min of delivering chilled infusate, the least effective cooling configuration was administering coolant directly through a non-inflated BGC, achieving a 1.2°C reduction in predicted brain temperature. The most effective cooling configuration was the co-axial combination of an insulated catheter and a fully inflated BGC, achieving a 7.8°C reduction in predicted brain temperature. Without proximal blood flow control (BGC inflation), high catheter flow rates were required to overcome rewarming from native ICA flow. Conclusions: These findings emphasize the impacts of catheter flow rate, catheter insulation, and competing warm blood flow on cooling efficiency.