Neuropathological hallmarks during the chronic phase of ischemic stroke in mice and humans.

An-Gong-Niu-Huang-Wan ameliorates neurovascular uncoupling and facilitates recovery after cerebral ischemic stroke by mediating P2X7 receptor inhibition.

Neurologic outcomes after pediatric large vessel occlusion (LVO) stroke are poor. In the absence of a pediatric randomized clinical trial, cohort and registry studies have demonstrated improved outcomes with thrombectomy compared with medical management alone. However, the benefit of thrombectomy in children with LVO and mild presenting symptoms remains uncertain. Our objective was to determine if thrombectomy is associated with superior functional outcomes compared with medical management alone in pediatric patients with acute LVO stroke and mild presenting symptoms. We undertook a case-control study pooling individual patient data from 4 published cohort studies on pediatric LVO stroke (Save ChildS, Save ChildS Pro, KidClot, Pediatric LVO Stroke Study), with patients treated at 75 centers across Europe, North America, and Australia between 2000 and 2023. Patients ≤18 years of age with acute LVO stroke on imaging and pediatric NIH Stroke Scale score ≤5 on admission were included. Patients treated with endovascular thrombectomy were compared with those treated with medical management alone. The primary clinical outcome was the functional status at 3 months after stroke, measured using the pediatric modified Rankin Scale and compared between groups using ordinal regression analysis. The primary safety outcome was the rate of symptomatic intracerebral hemorrhage. Pooled data identified 63 pediatric patients (female: n = 21, 33.3%; mean age 9.6 years, SD 5.1, range 0.5-18.0) who met the inclusion criteria. The cohorts were well balanced for IV thrombolysis status, age, sex, site and side of occlusion, ASPECTS, and stroke etiology. Thrombectomy treated patients (n = 25) had significantly better pediatric modified Rankin Scale scores at 3 months than medically managed patients (n = 38; odds ratio 5.5 [95% CI 1.22-24.81]; p = 0.027). In the medical management group, n = 13 (34.2%) of patients had early neurologic deterioration in the first 24 hours, compared with only one patient in the thrombectomy group (4%, p = 0.005). No symptomatic intracerebral hemorrhages occurred in either group. Thrombectomy in pediatric LVO stroke with mild presenting symptoms results in improved clinical outcomes compared with medical management alone and may prevent early neurologic deterioration. These findings can assist treating teams with acute clinical decision making in this complex clinical situation. This study provides Class III evidence that in pediatric patients with acute LVO stroke and mild presenting symptoms, thrombectomy results in better functional outcomes compared with medical management alone.

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.

Relationship between β-arrestin1-GAPDH interaction and the DADLE-mediated protection of brain microvascular endothelial cells from hypoxia-ischemic/reperfusion injury.

Despite major advances in intravenous thrombolysis and endovascular thrombectomy, nearly half of patients with acute ischemic stroke fail to achieve functional recovery even after technically successful recanalization. The recanalization-reperfusion gap-the discordance between angiographic vessel opening and tissue-level perfusion recovery-has brought thromboinflammation, the pathological interplay of coagulation and innate immunity, to the forefront of stroke biology. Neutrophil extracellular traps, platelet-leukocyte aggregates, complement activation, and vessel wall inflammation render clots resistant to lysis, promote microvascular obstruction and the no-reflow phenomenon, and amplify ischemia-reperfusion injury. These insights reframe stroke not solely as a problem of reopening arteries, but as an inflammatory disorder in which thrombus biology, microcirculatory flow, and inflammatory injury determine outcome. In this review, we outline the key thromboinflammatory challenges-recanalization resistance, no-reflow, and reperfusion injury-and discuss therapeutic opportunities that emerge from this framework. These include enzymatic neutrophil extracellular traps-targeting, adjunctive anti-inflammatory agents, biomarker-guided precision approaches, and novel device technologies that exploit or mitigate thrombus biology. Collectively, these strategies support a paradigm shift in stroke care: from procedure-focused reperfusion to biologically informed interventions that integrate vascular and immune determinants of outcome.

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.

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.

Focal cerebral arteriopathy-inflammatory type (FCA-i) is a leading cause of pediatric arterial ischemic stroke, but diagnostic challenges persist, particularly in East Asian populations where moyamoya disease (MMD) prevalence is high. The focal cerebral arteriopathy severity score quantifies arteriopathy severity but has not been validated in East Asian cohorts. We aimed to validate the focal cerebral arteriopathy severity score in Korean pediatric patients with FCA-i and compare temporal progression patterns with unilateral MMD. We conducted a retrospective cohort study of children with arterial ischemic stroke presenting to Seoul National University Hospital between January 2002 and December 2024. Patients were classified according to the Childhood Arterial Ischemic Stroke Standardized Classification and Diagnostic Evaluation criteria. The focal cerebral arteriopathy severity score was applied to serial magnetic resonance angiograms at baseline, peak severity, and final follow-up. Among 216 children with arterial ischemic stroke, 132 patients (61.1%) demonstrated arteriopathy, including 49 with FCA-i (median age, 8.6 [interquartile range (IQR), 6.4-11.3] years; 55% male), 60 with MMD (median age, 5.7 [IQR, 3.1-9.2] years; 43% male), and 13 with arterial dissection (median age, 7.0 [IQR, 3.1-10.4] years; 62% male). In FCA-i patients, the severity score correlated significantly with baseline infarct burden (ρ=0.42; P=0.0069) and exhibited characteristic monophasic evolution with early peak at 2 months followed by gradual recovery reaching lowest values at 11 months. Patients with unilateral MMD demonstrated consistently higher severity scores at all timepoints compared with FCA-i (baseline: 6.0 versus 2.0; final: 8.0 versus 3.0; P<0.001) without radiographic recovery. A baseline severity score ≥8.0 predicted contralateral progression in unilateral MMD with an area under the curve of 0.962 (sensitivity, 0.83; specificity, 0.91). The focal cerebral arteriopathy severity score demonstrates validity as a dynamic biomarker for monitoring FCA-i in Korean pediatric patients, exhibiting characteristic monophasic recovery patterns that distinguish it from progressive unilateral MMD.

This cross sectional analytical study was aimed to compare the in-hospital outcome (changes in LVEF, TIMI flow after PCI, major bleeding, acute stroke, mortality, re-infarction, hypotension, cardiogenic shock and arrhythmia) of pharmacoinvasive strategy versus pPCI in STEMI patients. This study was conducted in Ibrahim Cardiac Hospital and Research Institute (ICHRI), Dhaka, Bangladesh from January 2020 to June 2022; to compare the in-hospital outcome of pharmacoinvasive strategy using Tenecteplase with that of pPCI in the management of patients with STEMI. The study included a total of 100 cases of STEMI - randomized to pPCI (n=50) and pharmacoinvasive strategy (n=50). The in-hospital outcome (efficacy and safety) of the two strategies were studied, where efficacy was determined in terms of positive outcome (changes in LVEF and TIMI flow after PCI) and complications (death, re-infarction, acute stroke, hypotension, major episode of bleeding, cardiogenic shock and arrhythmia) experienced by the two groups. The mean age of the pPCI group was 52.9 years and that of pharmacoinvasive group was 56.2 years (p=0.139). Males were predominant in both the study groups; however, males were considerably higher in the pPCI group than that in the pharmacoinvasive group (p=0.054). Although insignificant changes in LVEF and TIMI grade flow (TIMI; p=0.380) between two groups but significant changes of LVEF and TIMI flow were observed in individual group in respect to pre and post PCI (LVEF; pPCI= 0.004 PhI, p=0.005 and TIMI flow; pPCI=0.005, PhI, p=0.004). The distributions of risk factors were almost alike between the two study groups. However, DVD and TVD were significantly higher in pharmacoinvasive group than those in the pPCI group (p=0.010). As outcome was compared between groups, the incidences of death (6.0%) and stroke (8.5%) were observed in pharmacoinvasive group alone. The incidence of hypotension was much higher in the pharmacoinvasive group (42.5%) than that in the pPCI group (16.0%) (p=0.004). Major bleeding episode was much higher in the pharmacoinvasive group (8.5%) than that in the pPCI group (2.0%) (p= 0.162). While pPCI receiving STEMI patients regain nearly full-patency of the culprit vessel. Almost similar result observed in patients received pharmacoinvasive strategy. However; small proportions of patients in pharmacoinvasive strategy cause stroke which may be fatal. Hypotension and major bleeding are also common in pharmacoinvasive strategy than that in pPCI strategy. The pPCI is preferred to pharmacoinvasive strategy if STEMI patients present themselves early in PCI-capable center. However, pharmacoinvasive strategy is a reasonable alternative for patients where pPCI could not be done within the recommended time.

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

Corrigendum to "Exploring the Evolution of Cortical Excitability Following Acute Stroke".

Acute haemorrhagic strokes are most common in people with hypertension, which causes high morbidity and mortality in Bangladesh. In this study, we investigated that whether serum potassium level is associated with risk of haemorrhagic strokes in hypertensive patients or not. We conducted a cross-sectional descriptive study that was carried out in the Department of Medicine and Neurology of Mymensingh Medical College Hospital, Mymensingh from December 2019 to May 2020. Total 100 patients (Mean age: 59.5±15 years, 58% male and 42% female) of hypertension with acute haemorrhagic stroke were enrolled in this study considering inclusion (both sex, CT scan proven stroke) and exclusion criteria (patients with congestive cardiac failure, conn's syndrome and kidney diseases). Our results showed that significant number of patients (34.0%) had potassium imbalance, with hypokalaemia (k+ <3.5) present in 31.0% study patients and hyperkalaemia (k+ >5) found in 3.0% patients. The present study also revealed that majority of patients having potassium imbalance had lower ICH score. From these findings we can conclude that hypokalemia may be responsible for subsequent increase in hemorrahagic stroke incidents in hypertensive patients. However, association between severity of acute hemorrahagic stroke and potassium imbalance was found not significant.

Mobile stroke units (MSUs) aim to expedite acute stroke management when compared with conventional emergency medical services (EMS). Despite the growing body of evidence surrounding MSUs and acute ischemic stroke, experience with intracerebral hemorrhage (ICH) in MSUs has been lacking. We aimed to evaluate the impact of MSU transportation, compared with EMS, on times to diagnosis and goal-directed treatment in patients with ICH. Retrospective analysis of patients with acute ICH triaged by MSU or EMS from January 2018 to December 2022 was performed at 2 tertiary institutions, the Cleveland Clinic (OH) and Stony Brook University (NY). In the EMS cohort, only patients seen between 08:00 and 20:00, corresponding to the operating hours of MSU, were included. Primary outcomes included diagnosis by computed tomography, administration of antihypertensives, and time to goal systolic blood pressure (<160 mm Hg). Analyses included descriptive statistics and multivariable regression modeling of log-transformed time metrics, adjusting for important patient demographic and clinical characteristics. Among 540 patients screened with ICH, after removing those with exclusion criteria, 218 MSU patients were compared with 192 EMS patients. Cohorts had similar baseline demographics, majority male (53.7% MSU versus 49.5% EMS), mean age 67±14 and 68±16, respectively. MSUs reduced time to diagnosis by 28% (β=0.72 [95% CI, 0.62-0.82]; P<0.001). Antihypertensives were administered to 78% of MSU patients, whereas not routinely given to EMS-transported patients until emergency department arrival. This facilitated a time reduction of 54% in the administration time of antihypertensive medications in MSU compared with EMS transported patients (β, 0.46 [95% CI, 0.36-0.59]; P<0.001). With 87% of MSU patients achieving blood pressure goal within 1 hour from last known well, compared with 60% in EMS (P<0.001). MSUs provide faster diagnosis and medical treatment for patients with acute ICH than patients transported by conventional EMS.

Acute stroke is frequently complicated by new-onset cardiac or thromboembolic events, referred to as Stroke-Heart Syndrome (SHS). The role of stroke subtype and lesion location in determining SHS risk remains underexplored. We conducted a retrospective analysis of data from the hospital-based Perugia Stroke Registry (March 2005-September 2019). Patients with acute neurological symptoms were classified as ischaemic stroke (IS) or haemorrhagic stroke (HS) based on neuroimaging. Logistic regression identified predictors of stroke subtype and in-hospital complications. Subgroup analyses compared first-ever versus recurrent strokes, and lesion location (lacunar, non-lacunar anterior, or non-lacunar posterior for IS; typical versus atypical for HS). The primary outcome was a composite of all-cause death, cardiac events and venous thromboembolic events during Stroke Unit stay. Secondary outcomes were each component. Among 2080 patients (mean age 72.8 ± 12.5 years; 57% male), 1788 (86%) had IS and 292 (14%) HS. During Stroke Unit stay (median 8 days, IQR 5-14), HS patients had higher rates of the composite outcome (26% vs 14%) and all-cause death (21.2% vs 8.8%) than IS. In IS, non-lacunar posterior and anterior strokes were associated with increased risk of composite outcome (OR 1.97, 95%CI 1.10-3.63; OR 1.61, 95%CI 0.96-2.81) and all-cause death (OR 3.35, 95%CI 1.35-9.51; OR 2.90, 95%CI 1.28-7.79) versus lacunar strokes. Among HS, atypical lesions increased risk of composite outcome (OR 2.51, 95%CI 1.24-5.22) and all-cause death (OR 2.80, 95%CI 1.31-6.17). Lesion location is a key determinant of SHS. Non-lacunar posterior stroke and atypical HS predict higher mortality and cardiovascular complications.

Long-term Complications of Venous Thromboembolism: A Practical Guide.

BackgroundStroke remains a leading cause of long-term disability worldwide. Robotic-assisted rehabilitation, particularly with the Hybrid Assistive Limb (HAL), has emerged as an innovative approach to enhance motor recovery and functional outcomes. HAL is a wearable exoskeleton that detects bioelectrical signals and provides real-time support, offering unique opportunities for task-specific and intensive neurorehabilitation.ObjectiveThis narrative review summarizes recent clinical evidence on the application of HAL in stroke rehabilitation, focusing on its effects on gait, upper limb recovery, activities of daily living (ADL), and safety, while discussing its limitations and future directions.MethodsA literature search of PubMed and Scopus was conducted for studies investigating HAL-assisted rehabilitation in stroke patients. Eligible studies included randomized controlled trials, systematic reviews, pilot studies, and relevant narrative reviews.ResultsEvidence from randomized and non-randomized studies suggests that HAL-assisted rehabilitation can improve gait velocity, balance, and, to a lesser extent, upper limb function in both acute and chronic stroke populations. Several systematic reviews and RCTs (2022-2025) have confirmed its potential benefits compared to conventional physiotherapy, though findings remain heterogeneous. HAL is generally safe and well tolerated, but high costs, limited availability, and methodological variations across studies constrain generalizability.ConclusionHAL-assisted rehabilitation represents a promising adjunct to conventional stroke therapy, with growing evidence supporting its efficacy in motor recovery. However, current data are limited by small sample sizes, inconsistent protocols, and lack of long-term follow-up. Large-scale, multicenter randomized controlled trials are warranted to establish its clinical utility, cost-effectiveness, and integration into routine care.

The optimal antiplatelet regimen for branch atheromatous disease (BAD)-related stroke remains uncertain. This study aimed to compare the clinical outcomes of dual antiplatelet therapy (DAPT) vs. single antiplatelet therapy (SAPT) in these patients. From the multicenter prospective BAD-study, we collected consecutive patients with BAD who received DAPT and SAPT. Propensity score matching (PSM) was used to balance baseline characteristics. The primary efficacy endpoint was an excellent outcome, defined as a modified Rankin Scale score of 0 to 1 at 90 days. The safety endpoint was bleeding events within 7 or 90 days. A total of 449 patients were enrolled in the analysis, with a median age of 60 years and a median National Institutes of Health Stroke Scale score of 3 at admission. After PSM, there were 112 patients in the SAPT group and 171 patients in the DAPT group, with well-balanced baseline characteristics. Excellent outcome occurred in 69.6% of the SAPT group and 79.5% of the DAPT group (odds ratio, 0.590; 95% confidence interval, 0.341 to 1.022; p = 0.059). No significant differences were observed in other efficacy outcomes between the two groups. In exploratory subgroup analysis, no significant treatment-by-subgroup interactions were observed, and after correction for multiple comparisons, no within-subgroup differences remained statistically significant. No increased bleeding risk was observed in DAPT. In acute BAD-related stroke, DAPT was safe but not statistically superior to SAPT for excellent functional outcome; however, its numerical trend toward benefit warrants further investigation.

Cardiovascular Complications During Delivery Hospitalizations in Patients With Infective Endocarditis.

Risk Stratification in Patients with TASC II D Aortoiliac Occlusive Disease Undergoing Revascularization: Validation of the CHA2DS2-VA Score for Long-Term Outcomes.