Multiomics reveals fatty acid metabolism and immune remodeling in retinal artery occlusion.

The efficacy of endovascular treatment for acute large vessel occlusion strokes has been demonstrated, but whether it can improve functional outcomes in patients with acute ischemic stroke (AIS) who only present with severe large vessel stenosis without occlusion has not yet been studied. This study investigates the effectiveness of immediate angioplasty or stenting on functional outcomes in AIS patients with severe intracranial stenosis without occlusion. We retrospectively included patients with AIS with symptom onset within 24 hours and imaging-confirmed severe intracranial stenosis (70%-99%, Warfarin Asprin Symptomatic Intracranial Disease criteria) of the culprit vessel from 7 centers in China between January 1, 2020, and December 31, 2024. We compared patients undergoing immediate angioplasty or stenting with those receiving standard medical treatment (SMT) alone. The primary outcome was the distribution of modified Rankin Scale (mRS) scores at 90 days. The treatment effect was estimated through multivariable adjusted models and inverse probability of treatment weighting (IPTW). Safety outcomes included symptomatic intracranial hemorrhage (sICH) within 24 hours and mortality within 90 days. A total of 242 patients were included, with a mean age of 65.7 years, and 86 patients (35.5%) were female. Ninety-six (39.7%) patients underwent immediate angioplasty or stenting, and 146 (60.3%) received SMT. The median 90-day mRS score was 1 (interquartile range 0-3) in the immediate angioplasty or stenting group and 1 (interquartile range 1-3) in the SMT group. The immediate angioplasty or stenting group showed a shift toward better functional outcomes on the mRS scores (adjusted common odds ratio [OR] 2.73 [95% CI 1.49-5.00], p = 0.001; after IPTW, OR 2.50 [95% CI 1.72-3.63], p < 0.001). There was no significant difference in the incidence of sICH (1.0% vs 1.4%; adjusted risk ratio 0.36 [95% CI 0.02-5.35], p = 0.46) or mortality (2.1% vs 1.4%; adjusted hazard ratio 1.01 [95% CI 0.92-1.11], p = 0.93). Among patients with AIS with severe intracranial stenosis without occlusion, immediate angioplasty or stenting was associated with improved 90-day functional outcomes compared with SMT alone. No significant difference was observed in the incidence of sICH or mortality. This study provides Class III evidence that in AIS patients with severe intracranial stenosis, immediate angioplasty or stenting was associated with improved 90-day functional outcomes compared with SMT.

Recent randomized trials reported no overall functional benefit of endovascular treatment (EVT) for distal medium-vessel occlusion (DMVO) and did not identify consistent effect modifiers to guide patient selection. Consequently, the role of EVT-particularly for M2 occlusions-remains controversial. We investigated whether baseline clinical severity modifies the association between successful recanalization and 90-day outcome in patients with M2 occlusion. Multicenter retrospective cohort study at 2 tertiary stroke centers including consecutive adults with acute ischemic stroke due to M2 occlusion (January 2015-January 2023) triaged by multimodal CT and treated with EVT. The primary end point was functional independence (modified Rankin Scale [mRS] ≤ 2) at 90 days. Secondary end points included symptomatic intracerebral hemorrhage (sICH), mRS 0-1, and penumbra salvage volume (PSV). The primary analysis used multivariable logistic regression with baseline National Institutes of Health Stroke Scale (NIHSS) modeled linearly and an NIHSS×recanalization (modified Thrombolysis in Cerebral Infarction [mTICI] ≥2b) interaction term. Johnson-Neyman probing and inverse probability weighting (IPW) were applied; a supplementary restricted cubic spline analysis was performed to explore potential nonlinearity. Among 147 patients, 85 (58%) achieved successful recanalization. The mean age was 74 years (SD 13), and 47% were female. Higher baseline NIHSS (adjusted odds ratio [aOR] 0.83 per point, 95% CI 0.73-0.94) and older age (aOR 0.96 per year, 95% CI 0.94-0.99) were associated with lower odds of functional independence. NIHSS significantly modified the association between recanalization and outcome (interaction p = 0.03). The magnitude of the association between successful recanalization and functional independence was larger at higher NIHSS. Model-based estimates suggested a descriptive crossover around NIHSS 10, whereas statistical evidence of benefit emerged only at higher NIHSS values. Successful recanalization was associated with greater PSV (+33 mL, p = 0.01). In the PSV interaction model, onset-to-imaging time differed by recanalization status (p < 0.01): time was positively associated with PSV in the mTICI ≤2a group, but near zero in mTICI ≥2b. IPW analyses were concordant. sICH occurred in 8.2% vs 4.8% (p = 0.42). In M2 occlusions, the magnitude of the association between successful recanalization and functional independence was larger at higher NIHSS and not reliably demonstrable at lower NIHSS. These findings support a severity-informed, individualized EVT approach while remaining hypothesis-generating rather than prescriptive for specific NIHSS thresholds. Major limitations include the retrospective observational design and potential residual confounding.

Growing evidence for reperfusion therapies in pediatric acute ischemic stroke (AIS) increases the importance of timely diagnosis within treatment windows. We therefore aimed to describe 24-year trends and associated factors of diagnostic delay. We conducted a nationwide retrospective cross-sectional study including 314 children aged 28 days to 16 years from the Swiss Neuropediatric Stroke Registry (2000-2023). The primary outcome was time from stroke onset to diagnosis (TOD). Trends for diagnoses beyond intravenous thrombolysis (≥4.5 hours) and thrombectomy (≥24 hours) windows were assessed with multivariable logistic regression, and for continuous TOD with robust linear regression. Prespecified covariates were retained in multivariable models if associated with the outcome in univariable analyses. Analyses were stratified by AIS onset location (out-of-hospital and in-hospital). Median TOD was 26.9 hours (interquartile range, 10.1-91.5) between 2000 and 2023. During this period, the proportion diagnosed beyond the thrombolysis window decreased significantly in the overall cohort from 90.9% to 77.5% (adjusted odds ratio per calendar year 0.94 [95% CI, 0.88-1.00]) and in out-of-hospital AIS from 88.1% to 74.1% (adjusted odds ratio, 0.91 [0.84-1.00]). No significant change was observed beyond the thrombectomy window diagnoses. Continuous TOD decreased significantly only in in-hospital AIS (β=-4.3 [-7.2 to -1.5]). Older age (β=-1.8 [-2.9 to -0.8]), higher pediatric National Institutes of Health Stroke Scale (β=-1.2 [-2.1 to -0.4]), and facial palsy (β=-19.4 [-30.2 to -8.5]) were associated with shorter TOD, and nonspecific symptoms (β=110.0 [72.5-147.5]) with longer TOD. Out-of-hospital TOD was shorter when patients presented to a stroke center compared with other presentation sites. Posterior-stroke symptoms were associated with diagnoses beyond the thrombolysis window. Despite decreasing proportions of beyond-thrombolysis window diagnoses in out-of-hospital AIS and decreasing TOD in in-hospital AIS, most diagnoses occur beyond reperfusion windows. Goals to decrease delay include raising awareness of posterior-stroke signs and AIS in younger children, and strengthening direct-to-stroke center pathways.

Multiparametric AI-based perfusion analysis outperforms Tmax thresholding for critically hypoperfused tissue estimation in acute ischemic stroke undergoing admission MRI.

As new evidence on the evaluation and management of patients with acute ischemic stroke continues to emerge, the American Heart Association/ American Stroke Association released its latest guidelines for the early management of acute ischemic stroke. These guidelines, for the first time, incorporate evidence-based recommendations for assessment and interventional management of pediatric patients with acute ischemic stroke. This update emphasizes on the new pediatric-specific recommendations and also discusses key differences from other pediatric stroke guidelines.

Disparities in interfacility transfer of patients with acute ischemic stroke have been identified at the regional level, but a national analysis has not been conducted. This study aims to evaluate patient-level trends and disparities in transfer rates based on sex, race, ethnicity, and insurance status using the Get With The Guidelines-Stroke registry. The Get With The Guidelines-Stroke registry was used to identify patients admitted with acute ischemic stroke between January 2016 and December 2021. We examined patient transfer rate by race/ethnicity groups and by patient insurance status. Odds of transferring out among each demographic group were calculated using a multivariable generalized linear mixed-effect model accounting for patient- and hospital-level confounders. Models were stratified by sex to test for any potential interaction between sex and race/ethnicity or insurance status. Among 776 556 patients transferred out of 1333 sites, Hispanic and Black patients had lower odds of being transferred compared with non-Hispanic White patients among both men and women after adjustment for stroke severity and hospital characteristics (odds ratio [OR], 0.79 [95% CI, 0.74-0.84] for Hispanic women; OR, 0.88 [95% CI, 0.83-0.93] for Hispanic men; OR, 0.80 [95% CI, 0.76-0.83] for Black women; and OR, 0.84 [95% CI, 0.81-0.88] for Black men). Differences in transfer frequency were also noted based on insurance status. In the unadjusted model and model adjusted for stroke severity, patients of all non-Medicare payment groups had higher odds of being transferred out compared with Medicare patients. However, after also adjusting for hospital characteristics, patients with Medicaid had a lower frequency of transfer compared with patients with Medicare among men and women (OR, 0.75 [95% CI, 0.71-0.78] for women with Medicaid; OR, 0.78 [95% CI, 0.75-0.82] for men with Medicaid). In this large, nationwide cohort of patients with acute ischemic stroke, Black and Hispanic patients were less likely to be transferred than non-Hispanic White patients, and patients with Medicaid were less likely to be transferred than patients with Medicare. Further work is needed to understand the contributors to this disparity and the impact on access to high-quality stroke care.

Atrial fibrillation/flutter at presentation is associated with worse functional outcome in acute ischemic stroke patients treated with thrombolytic therapy: A multicenter retrospective cohort study.

This study investigates the degree of the perceived risk of intravenous thrombolysis in acute cerebral infarction among surrogate decision-makers and the factors influencing their propensity to make decisions about thrombolysis. An investigation was conducted on a cross-sectional basis. We recruited participants using a purposive sampling technique. All participants were recruited from the Advanced Stroke Centre in a tertiary care general hospital from January 2022 to December 2022. A total of 201 Surrogate Decision-Makers completed the survey. Using a self-designed questionnaire, the instrument of this survey contains three aspects of general information including risk perception level survey, propensity for thrombolysis, and consisting of 18 questions. Risk perception consists of three dimensions: economic risk perception, psychosocial risk perception, and physical functioning risk perception, and each dimension is scored in the range of 3-15 points. Higher scores indicate stronger risk perception. The mean risk perception score of acute ischemic stroke surrogate decision-makers was (11.26 ± 2.72). The average score of psychosocial risk perception was (10.71 ± 2.34); the score of physical function risk perception was (11.00 ± 2.37). The highest proportion of those choosing conservative treatment was 46.8%. The percentage of those willing to thrombolize was 27.4%, and those who were unsure about it was 25.9%. The degree of perceived economic risk, perceived psychosocial risk, and perceived physical function risk all had a significant negative effect on the propensity to make decisions about thrombolysis after excluding the confounding interference of different ages, education levels, and monthly per capita household income. This study found a significant effect of risk-perception of the surrogate decision-maker on treatment propensity. Healthcare professionals should pay attention to guiding surrogate decision-makers to establish correct disease perception and risk-perception through effective communication during thrombolysis communication in acute ischemic stroke to relieve their decision-making pressure, shorten decision-making time and reduce Door-to-Needle time to improve patient prognosis and increase the rate of thrombolytic therapy. This study is a questionnaire survey conducted by the investigator and no patient or public participation is required. The risk perception of surrogate decision-makers is likely to play an essential role in the decision-making process. However, increased risk perception and prolonged thrombolysis are due to a lack of knowledge about thrombolysis among surrogate decision-makers. Generalizing the need for intravenous thrombolysis may improve the rate of thrombolysis and thus provide clinical benefit to patients.

Blood pressure variability (BPV) has emerged as a prognostic hemodynamic marker in acute ischemic stroke (AIS), with observational studies consistently associating early systolic fluctuations with infarct progression, neurological deterioration, hemorrhagic transformation, and worse functional outcomes. Whether BPV directly mediates injury or primarily reflects underlying stroke severity and physiological instability remains uncertain. Biologically plausible mechanisms exist in the context of impaired cerebral autoregulation, where systemic pressure fluctuations may translate into cerebral perfusion instability, particularly in the ischemic penumbra and during reperfusion. Despite consistent associations, clinical interpretation of BPV is limited by substantial heterogeneity in measurement methods, monitoring frequency, and analytic approaches. Most studies derive BPV from intermittently sampled oscillometric measurements, which may miss rapid fluctuations and are susceptible to artifacts. BPV is also strongly influenced by stroke severity, treatment intensity, and hemodynamic interventions, raising the possibility that observed variability reflects disease burden rather than an independent injury mechanism. This review summarizes evidence linking BPV to outcomes in AIS, examines methodological variability in its measurement, and highlights limitations restricting its translation into standardized monitoring or therapeutic strategies. BPV should be interpreted as a prognostic marker of disease severity rather than a confirmed causal mediator of injury, and its role as a modifiable treatment target remains unestablished. The HOPE randomized trial provided the first evidence that a reperfusion-guided, individualized systolic BP strategy may improve functional outcomes after endovascular thrombectomy (EVT), though findings require confirmation in larger trials.

Adjunctive Shuxuetong following thrombolysis in patients with acute ischemic stroke: A multicenter target trial emulation study.

Accurate identification and early warning of cognitive impairment after stroke.

Atrial fibrillation as an independent predictor of early epileptic seizures after acute ischemic stroke.

Sex differences in stroke cause, vessel anatomy, and thrombus composition are well established, yet whether these factors influence the efficacy of specific endovascular thrombectomy (EVT) techniques remains unknown. Here, we investigate sex-based differences in reperfusion outcomes across EVT techniques. Consecutive patients with anterior circulation large vessel occlusion including intracranial internal carotid artery and the M1 and M2 segments of the middle cerebral artery treated with EVT across 4 comprehensive stroke centers in the Greater Houston area (January 2021 to June 2024) were included from a prospectively maintained registry. EVT techniques were categorized as stent retriever, contact aspiration, or combined technique. The primary outcome was the first-pass effect (modified Thrombolysis in Cerebral Infarction 2c/3 after 1 pass). Secondary outcomes included achieving modified Thrombolysis in Cerebral Infarction 2c/3 within 2 passes, 90-day modified Rankin Scale score (0-2), intracerebral hemorrhage, symptomatic intracerebral hemorrhage, and mortality. Multivariable logistic regressions were used for binary outcomes adjusted for age, National Institutes of Health Stroke Scale score, atrial fibrillation, smoking, and prior thrombolysis. Linear regression was used for the number of thrombectomy passes. Among 724 patients that met inclusion criteria, 47% were female patients, the median age was 68 (interquartile range, 54-78) years, and the National Institutes of Health Stroke Scale score was 16 (interquartile range, 11-21). Presentation characteristics were balanced except for a greater rate of atrial fibrillation in female patients (23.0% versus 16.6%; P<0.05) and lower rates of intravenous thrombolysis in female patients (31% versus 40%; P<0.05). EVT techniques were comparable between sexes. The first-pass effect across the cohort was similar (female versus male patients, 37.9% versus 36.3%). In female patients, contact aspiration yielded higher odds of first-pass effect (adjusted odds ratio, 2.17 [1.07-4.35]) and modified Thrombolysis in Cerebral Infarction 2c/3 within 2 passes (adjusted odds ratio, 2.63 [1.32-5.26]) versus stent retriever, with fewer passes overall (β, 0.28; P<0.05). No difference in reperfusion outcomes was seen between EVT techniques in the male patients subgroup. Among patients receiving stent retriever as their first pass, female sex was associated with lower odds of achieving reperfusion within 2 passes (adjusted odds ratio, 0.43 [0.19-0.99]). This multicenter analysis provides the first evidence that EVT technique performance differs by sex. In female patients, contact aspiration achieved superior reperfusion with fewer passes than stent retriever. These findings highlight the importance of sex-stratified EVT trials and support individualized, precision-based device selection in acute ischemic stroke.

Acute ischemic stroke is a major cause of death and disability. Although reperfusion therapies are effective, early and lasting alterations in the microvasculature can limit recovery. Research has largely focused on microvascular impairment, whereas the pial arterial network remains relatively underexplored. Using the middle cerebral artery occlusion model and in vivo microscopy in mice, we assessed pial vessel dynamics during occlusion, recanalization, and the first 24 h of reperfusion. We analyzed vessel diameter, irregularity, resistance, blood flow, and microthrombus formation. Results revealed marked vasoconstriction throughout the pial network during occlusion, which persisted after recanalization, with vessel diameters reduced to 72 ± 27% (SD) of baseline at 24 h. Smaller pial vessels (<30 µm) reacted differently over time compared with larger vessels. Vessel irregularity and resistance increased and peaked at 24 h. A considerable proportion of vessels had impaired flow and microthrombi at all time points. Thrombosis risk in daughter vessels rose when a mother vessel contained a thrombus. In conclusion, recanalization is insufficient to avert early and persistent vascular dysfunction in this model. Our findings underscore the role of pial artery impairment in disturbed reperfusion and point to the need for complementary strategies to restore adequate blood flow and improve outcomes.NEW & NOTEWORTHY This study investigated vasoconstriction in the larger pial arteries, a network relatively underexplored in vascular stroke research, during and after ischemic stroke. By measuring vessel diameters along the entire vessel length, we uncovered effects of local constriction on vessel irregularity and resistance not reported before in vascular literature. By imaging during occlusion and hyperacutely after reperfusion, this study investigated thrombi formation and flow impairments at critical time points, providing insight lacking in prior research.

Ischemic stroke, the second leading cause of death and a primary source of severe disability in adults worldwide, is associated with high morbidity and mortality rates that correlate closely with the extent of neuronal damage. A critical strategy for improving patient outcomes is the early identification and rescue of the ischemic penumbra, a region at risk but potentially salvageable. However, accurately identifying and visualizing this penumbra poses a significant challenge in treatment and is crucial for predicting patient prognosis. Conventional magnetic resonance imaging (MRI) techniques often fail to delineate viable tissue effectively.Cleaved Caspase-3 (c-Casp3), a key executor of apoptosis, is specifically and highly expressed within the penumbra, making it an ideal molecular target for precise imaging. To address this challenge, we designed and constructed a multifunctional, enzyme-responsive MRI nanoprobe (FGAPT) for the molecular imaging of the ischemic penumbra. This probe capitalizes on the elevated expression of activated Caspase-3 during ischemic neuronal apoptosis, facilitating its specific accumulation and activation at the lesion site. As a result, there is a significant enhancement of the T1-weighted imaging signal, allowing for accurate delineation of the penumbra. This study establishes an imaging strategy for the precise identification of the ischemic penumbra, thereby presenting a paradigm for guiding individualized thrombolytic and neuroprotective interventions in ischemic stroke. The proposed methodology lays a robust imaging foundation for transitioning stroke management from a generalized therapeutic approach to personalized treatment optimization. STATEMENT OF SIGNIFICANCE: The precise delineation of the ischemic penumbra is critical for guiding therapy in acute ischemic stroke, yet remains a challenge for conventional imaging. To address this, we developed an enzyme-responsive magnetic resonance imaging (MRI) nanoprobe, FGAPT, for the molecular visualization of this salvageable tissue. This smart probe is engineered around a MRET mechanism, linking a superparamagnetic quencher (Fe₃O₄) and a paramagnetic enhancer (Gd-DOTA) with a peptide sequence specifically cleaved by activated Caspase-3-a key executor of apoptosis upregulated in the penumbra. Surface conjugation of a brain-targeting aptamer ensures blood-brain barrier penetration. In a rodent stroke model, the probe achieved high-contrast, specific T1-signal enhancement exclusively within the penumbra, as confirmed by spatial colocalization with histologically verified apoptotic cells. This Caspase-3-activated imaging strategy enables accurate differentiation between the infarct core and the ischemic penumbra. By directly visualizing a pivotal molecular determinant of cellular fate, our work provides a novel tool to advance stroke management from a rigid "time window" paradigm toward a precision "tissue window" approach.

Rapid local ischemic postconditioning may protect the brain after acute ischemic stroke, but its safety and optimal dosing in successfully reperfused patients after mechanical thrombectomy remain undefined. This investigator-initiated, prospective, adaptive, multicenter phase I single-arm dose-finding trial employed a Bayesian Optimal Interval (Bayesian Optimal Interval Phase I/II) design. Patients with anterior circulation large-vessel occlusion and modified Thrombolysis in Cerebral Infarction 2b/3 reperfusion were enrolled without randomization. Within 5 minutes of recanalization, rapid local ischemic postconditioning was delivered via a balloon-guiding catheter positioned at the ipsilateral C1-intracranial internal carotid artery, alternating inflation/deflation to interrupt antegrade flow. Six dose levels were prespecified by inflation/deflation durations and cycles: 15/15s ×5; 1/1, 2/2, 3/3, 4/4, and 5/5 minutes ×4. The dose-limiting toxicity (including malignant infarction, procedure-related complications requiring treatment, or other procedure-attributable serious adverse events) threshold was 15%. The efficacy target (absence of infarct growth >10 mL at 72 hours) was 60%. Doses were eliminated if the posterior probability that toxicity exceeded 15% was ≥0.95 or efficacy <60% was ≥0.90. The dose with the highest utility meeting these criteria was selected. Five cohorts (n=25, 5 each) were enrolled. Four cohorts received 2/2 minutes×4 (n=20): 14 met the efficacy end point (posterior probability true efficacy <60%, ≈0.15), and 1 had a dose-limiting toxicity due to large infarction growth (probability true toxicity >15%, ≈0.16). One cohort received 3/3 minutes×4 (n=5): 3 met the efficacy end point (probability true efficacy <60%, ≈0.31) and 2 had dose-limiting toxicities due to large infarction growth (probability true toxicity >15%, ≈0.95). This triggered the predefined safety rule, preventing further testing at 3/3-minute and higher doses. Bayesian Optimal Interval Phase I/II selected 2/2 minutes×4 as the optimal regimen with a favorable efficacy-toxicity profile. Rapid local ischemic postconditioning initiated immediately after thrombectomy was feasible. The 2/2 minutes×4 regimen met prespecified safety and efficacy thresholds and warrants evaluation in a larger, definitive trial. URL: https://www.clinicaltrials.gov; Unique identifier: NCT06526429.

A five-year comparative analysis of attending physician and non-attending initiated code stroke activations in a primary stroke center emergency department.

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.

Cerebral ischemia triggers a cascade of molecular events over minutes to days, which activate immune cells, inflammation, and coagulation, promoting cell death. These processes critically influence both short- and long-term outcomes in patients with stroke. In this review, we address the role of immune molecular and cellular factors, and the therapeutic approaches predicted to be targetable by specific agents under a timely application. We will focus on translational efforts targeting (thrombo)-inflammatory mechanisms, highlighting past missteps and current opportunities. Finally, we outline key mechanistic and methodological questions that may define a path forward.