Tudor G. Jovin

BACKGROUND: The impact of internal carotid artery tortuosity on achieving first-pass effect in mechanical thrombectomy has been described; however, middle cerebral artery (MCA) tortuosity remains understudied. We investigated the association of MCA tortuosity with radiographic and functional outcome using quantitative and qualitative measures. METHODS: The ARISE II study (Analysis of Revascularization in Ischemic Stroke With EmboTrap) was used to identify patients with anterior circulation stroke. MCA tortuosity was calculated using the Inflection Count Metric by 2 readers blinded to the angiographic/clinical outcomes. The total cohort was trichotomized into 3 groups (A, B, and C) based on M1 tortuosity tertiles, with group A representing the lowest tertile and group C representing the highest tertile. The primary efficacy end point was the achievement of first-pass expanded Thrombolysis in Cerebral Ischemia reperfusion ≥2c. A good functional outcome was defined as a 90-day modified Rankin Scale score of 0 to 2. Baseline and procedural data were compared between groups. RESULTS: A total of 168 patients with M1 or M2 occlusion and measurable MCA tortuosity were identified. Patients in group C were more likely to have renal disease and hyperlipidemia, whereas patients in group A were more likely to have hypertension ( P P =0.024). The rate of final expanded Thrombolysis in Cerebral Ischemia reperfusion ≥2c was higher in group A (87.5%) versus in groups B and C (77.8% and 66%, respectively; P =0.026); achieving modified Rankin Scale score of 0 to 2 was more likely in group A (77.8%) versus in groups B and C (74.5% and 52.7%, respectively; P =0.008). There were no differences in distal emboli or symptomatic intracranial hemorrhage. First-pass effect and angiographic outcomes were consistent with standard angle of curvature tortuosity. CONCLUSIONS: Patients with higher MCA tortuosity were less likely to achieve first-pass effect, successful reperfusion, and good functional outcome at 90 days postmechanical thrombectomy for acute ischemic stroke. REGISTRATION: URL: http://clinicaltrials.gov ; Unique identifier: NCT02488915.

BACKGROUND: The past decade has witnessed rapid growth of clinical trial programs in Europe and Asia, with randomized clinical trials (RCTs) publications from these regions outpacing those of the United States. However, limited data exist quantifying their relative influence on practice-defining results. Here, we evaluate these shifts by analyzing the geographic origin, funding source, and clinical impact of practice-changing RCTs. METHODS: From the 2018 and 2026 American Heart Association/American Stroke Association Acute Ischemic Stroke guidelines, we identified RCTs supporting new recommendations and extracted geographic origin (China/Europe/United States/Other), funding source (government/academic/nonprofit versus industry (private/mixed); National Institutes of Health versus non-National Institutes of Health), and research topic (endovascular therapy, thrombolysis, imaging, poststroke care, and prehospital and systems of care). Analyses used unweighted, reference-density-weighted, and clinical-impact-weighted strategies. Temporal trends were assessed using the χ ² /Fisher exact tests, with the Rao-Scott adjusted χ ² tests accounting for weighting. RESULTS: We identified 21 new recommendations (47 RCTs) in 2018 and 45 (89 RCTs) in 2026. In 2018, Europe led (51.1%), followed by the United States (31.9%), while China and other regions contributed minimally. By 2026, Europe remained first (36%), China rose to second (29.2%), and the United States declined to the smallest share (14.6%), across all weighted analyses ( P P <0.01 across all weighted strategies). CONCLUSIONS: In this analysis, we identify a shift in practice-guiding research away from United States–based clinical trials and increasingly towards Europe and China. United States–based RCTs fell from the second most cited to the least cited sources of recommendations. National Institutes of Health–funded RCTs fell from nearly one-quarter of guideline-cited RCTs in 2018 to <5% in 2026, highlighting increasing reliance on non-US studies to inform US clinical care.

Time to endovascular thrombectomy (EVT) is a critical determinant of outcomes for large vessel occlusion (LVO) strokes presenting within 6 hours of onset. Its impact in the extended (6-24-hour) window remains uncertain. We aimed to evaluate the association between treatment times and outcomes in this window. Individual patient-level data from 6 randomized trials enrolling patients in the extended window were pooled. The primary outcome was degree of disability at 90 days (modified Rankin Scale [mRS] 0-6). Secondary outcomes included functional independence (mRS 0-2), mortality, and symptomatic intracranial hemorrhage. Among 505 participants (median age 70 years; baseline NIH Stroke Scale 16; 51.3% female; advanced imaging selection 86.5%), 266 (52.7%) received EVT and 239 (47.3%) medical therapy alone. In EVT-treated patients, longer onset-to-randomization times were not associated with differences in disability (adjusted odds ratio [aOR] per 60 minutes 1.02; 95% CI 0.96-1.08; p = 0.53) or functional independence (aOR 1.06; 95% CI 0.95-1.17; p = 0.28). Conversely, control patients exhibited worse outcomes with increasing onset-to-randomization times (aOR for disability 0.93; 95% CI 0.87-1.00; p = 0.041; functional independence 0.84; 95% CI 0.73-0.97; p = 0.019), resulting in greater treatment benefit at later times (p-interaction = 0.033 and 0.003, respectively). No association was observed between onset-to-puncture or onset-to-reperfusion and outcomes in EVT patients. However, longer randomization-to-reperfusion times correlated with worse disability (aOR 0.58; 95% CI 0.37-0.91; p = 0.018) and lower functional independence (aOR 0.51; 95% CI 0.28-0.96; p = 0.038). This study demonstrates that the benefit of EVT is consistently preserved across the extended (6-24-hour) time window when patients are selected using advanced imaging criteria. In this highly selected population, enriched with slow progressors, the apparent increase in treatment effect with longer onset-to-presentation times reflects the validity of physiologic selection rather than true time insensitivity. However, this observation should not diminish the critical importance of time: imaging-based selection effectively resets the treatment clock, masking the harmful impact of prehospital delays. Notably, longer in-hospital delays were strongly associated with worse outcomes, reinforcing that "time is brain," even in extended-window cohorts.

The Circle of Willis (CoW) is an important collateral pathway, and its anatomy may influence intracranial flow patterns in the setting of atherosclerotic disease. This study describes the distribution of intracranial atherosclerotic disease (ICAD) and evaluates associations between ICAD presence across CoW vessel segments in the Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis - Hemodynamics (CREST-H) cohort. This retrospective analysis included 252 patients from the CREST-H trial with baseline Time-of-flight MR angiography (TOF-MRA) suitable for evaluation. TOF-MRA was used as a luminal surrogate to assess intracranial arterial narrowing and irregularity, rather than as a direct plaque-imaging technique. Intracranial arterial segments were assessed for luminal abnormalities compatible with ICAD, and the CoW was categorized based on circle completeness and anatomical pattern using Ayre's classification. Phi-coefficient was used to evaluate associations in ICAD presence across vessel segment pairs. ICAD was most frequently observed in the right (69.4%) and left (67.1%) intracranial ICA, followed by anterior and posterior circulation CoW segments. Complete, partially complete, and fully incomplete CoW was identified in 17.5%, 73.8%, and 8.7% of patients, respectively. Pairwise associations in ICAD presence were observed between the right ICA and right ACA (ϕ = 0.25, p < 0.001) and between contralateral paired vessels, including right and left ICA, PCA and ACA (all p < 0.001). No correlation was found between left ICA and left ACA (ϕ = 0.10, p = 0.08). In the atherosclerosis-enriched CREST-H cohort, ICAD was common and was most frequently seen in intracranial ICAs. Associations in ICAD presence were observed between selected ipsilateral and contralateral CoW vessel pairs. These findings are descriptive and may help provide preliminary data for future studies of intracranial atherosclerotic distribution in patients with carotid atherosclerotic disease.

BACKGROUND: Detection of large vessel occlusions using a deep learning (DL) algorithm for the anterior circulation has shown promising results. However, the role of DL algorithms in detecting posterior circulation large vessel occlusion (PC-LVO) remains uncertain. We aimed to evaluate the diagnostic performance of a DL algorithm (Methinks PC-LVO) for detecting PC-LVO using noncontrast computed tomography. METHODS: This is a retrospective, multicenter, observational cohort study that included patients with PC-LVO who underwent both noncontrast computed tomography and computed tomography angiography. The diagnostic performance of the DL algorithm was assessed by analyzing sensitivity, specificity, and area under the curve for PC-LVO detection of consecutive PC-LVO strokes. For comparative analysis, the area under the curve of the DL algorithm was also evaluated against the performance of a neuroradiologist interpreting noncontrast computed tomography. Ground truth labels were established through consensus readings by expert neuroradiologists. Subgroup analyses were performed according to clot location (proximal posterior cerebral artery and basilar artery) and National Institutes of Health Stroke Scale (NIHSS) score (NIHSS score ≥6, NIHSS score ≥8, and NIHSS score ≥10). RESULTS: A total of 196 patients were included, of whom 74 patients had PC-LVO. Among these, 43 had basilar artery occlusions, and 34 had proximal posterior cerebral artery occlusions. The overall sensitivity and specificity of the software were 55.4% and 80.9%, respectively, with an area under the curve of 0.72. The neuroradiologist achieved a sensitivity of 27.4% and specificity of 91.8%. Among patients with proximal posterior cerebral artery occlusion, sensitivity was 55.9%, whereas for basilar artery occlusion, it was 53.5%. When stratified by NIHSS score ≥10, sensitivity in the proximal posterior cerebral artery was 56.2%, and for the basilar artery with NIHSS score ≥10, it increased to 61.5%. CONCLUSIONS: Our initial experience with a DL algorithm for the detection of PC-LVO showed promising results. However, further improvements are required before the algorithm can be implemented in clinical practice.

BACKGROUND: Endovascular thrombectomy (EVT) has demonstrated benefits in patients with ischemic stroke and large-vessel occlusions, but its efficacy and safety in patients with the largest baseline infarcts (Alberta Stroke Program Early Computed Tomography Score [ASPECTS] 0–2), remain controversial. This study aimed to evaluate the efficacy and safety of EVT in early presenting patients with ASPECTS 0 to 2 compared with medical care alone. METHODS: This post hoc analysis of the multicenter, randomized LASTE trial ([Large Stroke Therapy Evaluation]; patients ≤80 years, ASPECTS 0–5, proximal anterior circulation large-vessel occlusion, randomization within 6.5 hours of last known well) evaluated the subgroup with ASPECTS 0 to 2, representing those with large baseline infarcts without an upper size limit, randomized to receive EVT plus medical care or medical care alone. Primary outcomes included the distribution of the modified Rankin Scale score at 90 days. Secondary outcomes included mortality, infarct volume growth at 24 hours, the incidence of symptomatic intracranial hemorrhage and modified Rankin Scale score at 180 days. The LASTE trial was conducted and reported in accordance with the CONSORT guidelines (Consolidated Standards of Reporting Trials). RESULTS: Median age was 72 years and 55.8% were women. Among the 181 patients with ASPECTS 0 to 2 (median core volume 156 mL [25th–75th percentiles, 121–204 mL]), at 90 days after randomization, EVT improved functional outcomes (generalized odds ratio, 1.81 [95% CI, 1.32–2.47]) and reduced mortality (38.4% versus 59.6%; relative risk, 0.64 [95% CI, 0.47–0.89]), which translated predominantly into an increase in the proportion of modified Rankin Scale score of 0 to 3 in the EVT group (31.4% versus 8.5%; relative risk, 3.69 [95% CI, 1.77–7.68]). A significant reduction in infarct growth volume was observed in the EVT group compared with medical care (mean difference, −70.3 mL [95% CI, −94.2 to −46.3]). Rates of symptomatic intracranial hemorrhage were 12.9% versus 4.5%, respectively (relative risk, 2.85 [95% CI, 0.94–8.60]). CONCLUSIONS: EVT improves functional outcomes and reduces mortality in patients with ASPECTS 0 to 2. These findings support the concept that in patients aged <80 years presenting within early time window (6.5 hours) with unlimitedly large infarct (predominantly selected using magnetic resonance imaging), the infarct size in isolation should not be used to disqualify patients from endovascular treatment. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03811769.

BACKGROUND: Adherence to healthy dietary patterns has been related to lower cardiovascular disease risk. However, few studies have examined prospective associations between adherence to different healthy dietary scores and the incidence of stroke and its subtypes. The aim of this study was to prospectively examine the associations between adherence to 4 recognized healthy dietary patterns and the risk of total and ischemic stroke in an existing dietary-based randomized controlled trial. METHODS: This is a secondary observational cohort analysis of 7447 participants at high cardiovascular disease risk enrolled in the PREDIMED trial (Prevención Con Dieta Mediterranea). Dietary scores for 4 healthy dietary patterns, including the Mediterranean, Dietary Approaches to Stop Hypertension (DASH), Mediterranean-DASH Diet Intervention for Neurodegenerative Delay diets, and the Planetary Health Diet Index, were derived from repeated food frequency questionnaires. Participants were classified into quintiles of cumulative average adherence of the 4 dietary scores. Multivariable-adjusted Cox proportional hazards models were used to estimate hazard ratios and 95% CIs for associations with the healthy dietary scores and risk of stroke and stroke subtypes. RESULTS: During a total of 31 024 person-years of follow-up (median, 4.3 years), 135 stroke cases were documented (112 ischemic and 23 hemorrhagic strokes). Comparing the highest versus the lowest quintile of dietary scores, the multivariable-adjusted hazard ratio of total stroke was 0.26 (95% CI, 0.14–0.51) for Mediterranean diet and 0.25 (95% CI, 0.13–0.51) for Mediterranean-DASH Diet Intervention for Neurodegenerative Delay diet, while no significant associations were observed for the DASH diet (adjusted hazard ratio, 0.76 [95% CI, 0.42–1.39]) or the Planetary Health Diet Index (adjusted hazard ratio, 0.57 [95% CI, 0.30–1.08]). Similar associations were observed for ischemic stroke. CONCLUSIONS: In individuals at high cardiovascular disease risk, greater adherence to the Mediterranean and Mediterranean-DASH Diet Intervention for Neurodegenerative Delay diets was associated with a lower risk of total stroke and ischemic stroke. REGISTRATION: URL: https://www.isrctn.com/ ; Unique identifier: ISRCTN35739639.

BACKGROUND: While rescue stenting (RS) is a recognized bailout strategy following failed endovascular thrombectomy for acute ischemic stroke with large vessel occlusion, first-line stenting (FLS) has emerged as a potential alternative to avoid vascular injury and improve outcomes. However, direct comparisons between these strategies remain limited. We conducted a comparative analysis of FLS versus RS using data from a large, multicenter international registry to evaluate their relative safety and effectiveness. METHODS: We conducted a comparative analysis of FLS versus RS using data from the RESISTANT registry (Registry of Endovascular Salvage for Intracranial Stenting in Thrombectomy-Refractory Stroke), a multicenter, international, retrospective cohort of patients with acute ischemic stroke treated with intracranial stenting during endovascular thrombectomy (2016–2023). Patients were categorized by stenting strategy: FLS (stent placed without prior thrombectomy) or RS (stent placed after failed thrombectomy). The primary effectiveness outcome was functional independence (modified Rankin Scale score, 0–2) at 90 days; the primary safety outcome was symptomatic intracranial hemorrhage. Propensity score inverse probability of treatment weighting was used to adjust for baseline differences. RESULTS: Among 827 patients, 723 were in the RS cohort (median age, 67 [interquartile range, 59–77] years; 64.2% male) and 104 in the FLS cohort (median age, 65.5 [interquartile range, 58.8–77] years; 72.1% male). Using FLS as the reference strategy, inverse probability of treatment weighting–adjusted analyses did not detect significant differences in functional independence (odds ratio [OR], 0.64 [95% CI, 0.38–1.07]) or symptomatic intracranial hemorrhage (OR, 0.93 [95% CI, 0.34–2.59]). No significant differences were observed in secondary outcomes, including successful reperfusion, mortality, or procedural complications. In the anterior circulation cohort (n=589), outcomes were likewise comparable (functional independence: OR, 0.62 [95% CI, 0.60–1.25]; symptomatic intracranial hemorrhage: OR, 0.81 [95% CI, 0.30–2.18]). Similarly, in the posterior circulation cohort (n=234), no significant differences were found (functional independence: OR, 0.82 [95% CI, 0.32–2.10]; symptomatic intracranial hemorrhage: OR, 0.81 [95% CI, 0.30–2.18]). CONCLUSIONS: In this study, no significant differences in safety or effectiveness were detected between FLS and RS strategies during endovascular thrombectomy for acute ischemic stroke. Prospective, randomized trials are needed to better define optimal treatment approaches.

Background: The past decade has witnessed rapid growth of clinical-trial programs in Europe and Asia, with randomized clinical trials (RCTs) publications from these regions outpacing those of the U.S. However, limited data exist quantifying their relative influence on practice-defining results. Here, we evaluate these shifts by analyzing geographic origin, funding source, and clinical impact of practice-changing RCTs. Methods: From the 2018 and 2026 American Heart Association/American Stroke Association (AHA/ASA) Acute Ischemic Stroke (AIS) Guidelines, we identified RCTs supporting new recommendations and extracted geographic origin (China/Europe/USA/Other), funding source (government/academic/non-profit vs. industry (private/mixed); NIH vs. non-NIH), and research topic (endovascular therapy (EVT), thrombolysis, imaging, poststroke care, and prehospital and systems of care). Analyses used unweighted, reference-density-weighted, and clinical-impact-weighted strategies. Temporal trends were assessed using the chi-square/Fisher’s exact tests, with Rao-Scott adjusted chi-square tests accounting for weighting. Results: We identified 21 new recommendations (47 RCTs) in 2018 and 45 (89 RCTs) in 2026. In 2018, Europe led (51.1%), followed by the U.S. (31.9%), while China and other regions contributed minimally. By 2026, Europe remained first (36%), China rose to second (29.2%), and the U.S. declined to the smallest share (14.6%), across all weighted analyses (p<0.01). NIH-funded trials declined significantly from 21.3% (unweighted), 27.4% (reference-density-weighted), and 27.3% (clinical-impact-weighted) in 2018 to 4.5%, 4.8%, and 3.4%, respectively in 2026 (p<0.01 across all weighted strategies). Conclusion: In this analysis, we identify a shift away from U.S.-based clinical trials and increasing contributions from China. U.S.-based RCTs fell from the second most cited to the least cited sources of practice-changing recommendations. NIH-funded research fell from nearly one-quarter in 2018 to <5% in 2026, highlighting increasing dependence on non-U.S. studies for U.S.-based care. These findings raise questions about the effectiveness of current AIS research paradigms in the U.S.

Purpose: The optimal anesthetic approach for intracranial stenting in acute stroke remains unclear. We compared outcomes of patients under general anesthesia (GA) versus local anesthesia or conscious sedation. Methods: The RESISTANT registry is a multicenter observational study on acute intracranial stenting during thrombectomy. Patients treated between January 2016 and June 2023 were included and stratified into GA and local anestesia/conscious sedation groups. The primary outcome was an adjusted shift analysis of the modified Rankin Scale (mRS) at 90 days. Secondary outcomes included mRS 0–2 at 90 days and final modified Thrombolysis in Cerebral Infarction (mTICI) 2c/3 scores. Safety outcomes were symptomatic intracranial hemorrhage (sICH) and mortality. Adjusted ordinal and logistic regression with mixed-effects models were performed. Results: Of 876 patients, 445 (50.8%) received GA. Median age was 67 years [59–77]; 567 (64.8%) were men. No differences were found in 90-day mRS (adjusted common OR = 1.256 [0.887–1.780], p = 0.199). Rates of functional independence (39.0% vs 44.5%; aOR = 0.956 [0.606–1.507], p = 0.846), mTICI 2c/3 (68.9% vs 68.7%; aOR = 0.941 [0.602–1.471], p = 0.790), and sICH (8.0% vs 8.6%; aOR = 0.769 [0.374–1.584], p = 0.477) were comparable. In-hospital (23.0% vs 12.0%; aOR = 2.39 [1.35–4.22], p = 0.003) and 90-day mortality (33.3% vs 21.1%; aOR = 2.017 [1.227–3.315], p = 0.006) were higher in the GA group. Conclusion: In patients undergoing intracranial stenting during thrombectomy, anesthesia modality was not associated with better outcomes. GA was linked to higher mortality, likely due to indication bias.