Stroke最新文献

Background: Cerebral angiography cannot directly assess the intimal surface of a vessel. The MicroAngioscope is a small and flexible catheter that allows visualization of the inside of the cerebral vasculature. Our objective is to report our first-in-human experience with the live visualization of intracranial vasculature using the MicroAngioscope.

Methods: This was a prospective, single-arm, national multi-center observational study of consecutive intracranial endovascular cases treated using the MicroAngioscope as an adjunct. This first-in-human study aimed at assessing the safety of the technology by prospectively collecting any procedural complications. A secondary end point was the successful visualization of the vasculature and the implants.

Results: The MicroAngioscope, used in 31 cases, was successfully delivered to the location of interest and allowed for a direct live visualization of the condition and the implant that had been deployed. There was no vessel injury based on cerebral angiography. The cases included 9 cases of carotid stent, 6 cases of flow diversion, 11 cases of transverse sinus stenting, 2 cases of aneurysm intrasaccular flow-disruption, 1 case of aneurysm treatment with stent-assisted coiling, and 2 cases of mechanical thrombectomy. All cases were successfully completed without complications. All patients were neurologically unchanged following their respective procedures. Angioscopy was helpful in making the diagnosis in the case of the carotid web, assessing vessel wall apposition immediately after flow diverter and venous stent deployment, and assessing the degree of strut coverage in both arterial and venous stents in follow-up.

Conclusions: This First-in-Human study demonstrated the early feasibility and safety of the MicroAngioscope in neurointerventional procedures. Further studies are needed to determine its relevance in daily practice.

Background: Abundant data link ApoE (apolipoprotein E)-ε2 with favorable outcomes in several neurological settings and in healthy subjects, but studies in relation to stroke outcomes are few. ApoE-ε2 activities are associated with poststroke cortical oscillations, which themselves are correlated with poststroke outcomes. The aim of this cohort study was to determine whether cortical oscillations could represent an endophenotype mediating the effects of ApoE-ε2 on poststroke function.

Methods: In 33 patients with recent stroke, resting EEG activity (3 minutes), APOE genotype, and functional outcome (GG scores) were measured. ANCOVAs and partial Pearson correlations were performed to validate the prerequisites for mediation analyses, in which EEG cortical power was tested as a mediator of the relationship between APOE-ε2 and functional outcome.

Results: ApoE-ε2 carriers showed higher ipsilesional beta power and lower ipsilesional theta power, both of which were linked to better functional outcomes. The principal mediation analysis revealed an indirect effect of ApoE-ε2 on functional outcome via ipsilesional M1 beta power (ACME, 14.79 [0.9-34.6], P=0.03*), explaining 14% of the average outcome. Exploratory mediation analyses further highlighted an indirect effect of ApoE-ε2 on functional outcome via ipsilesional M1 theta power (ACME, 48.2 [13.3-89.6], P=0.017*, explaining 43% of the average outcome. Ipsilesional M1 power in other frequency bands (delta, alpha, gamma) and contralesional M1 power across all frequency bands did not reveal significant mediation effects.

Conclusions: The mediation analysis results suggests that ApoE-ε2 supports a pro-repair environment, which may translate into more favorable cortical dynamics after stroke. Cortical oscillatory activity may be considered as an endophenotype that mediates the effects of ApoE-ε2 on functional outcome and could potentially be leveraged as a biomarker to develop personalized interventions targeting stroke recovery.

Background: Infants and toddlers with perinatal arterial ischemic stroke face a high risk for lifelong neuromotor impairments and multiple disabilities. Phase 3 clinical trial evidence is urgently needed to identify efficacious treatment to improve outcomes.

Methods: The I-ACQUIRE Phase 3 trial (Perinatal Arterial Stroke: A Multisite RCT of Intensive Infant Rehabilitation) is a 15-site randomized clinical trial of 2 dosages of I-ACQUIRE, a multicomponent, therapist-delivered intervention including key components of constraint-induced movement therapy compared with usual and customary treatment. The trial recruited children 8 to 36 months old with parent-reported perinatal arterial ischemic stroke, hemiparesis, good health, and no prior botulinum toxin or constraint-induced movement therapy. Central 1:1:1 randomization assigned children to High-dose I-ACQUIRE (6-hour sessions, 5 days/wk, 4 weeks), Moderate-dose I-ACQUIRE (3-hour sessions, 5 days/wk, 4 weeks), and Usual and Customary Treatment. Blinded assessments at baseline, end-of-treatment, and 6-months later include the Emerging Behaviors Scale (success defined as % with gains ≥7 points), the primary outcome for unilateral skills on the paretic arm-and-hand; and the Mini-Assisting Hand Assessment, the secondary outcome for bimanual activities. Parents also rate children's motor skills, treatment responses, and stress. Statistical analyses include 2-sample binomial tests for group differences and linear mixed regression models. The registered trial adheres to international trial reporting guidelines and has a parent council.

Results: This study protocol describes intervention components plus training and monitoring of treatment fidelity. The trial recruited N=216 children; 198 completed baseline assessments, and 168 (85 boys and 83 girls) qualified for the modified intent-to-treat sample. The mean age was 18.0 (SD=7.6) months. A majority had right-sided paresis (70%); 51% had seizures/epilepsy. Children varied widely in functional classification levels and parent ratings.

Conclusions: The trial sets a unique high threshold for efficacy and proposes sensitivity and exploratory analyses to consider differential response patterns to treatment. If 1 or both I-ACQUIRE dosages lead to significant improvements, then Phase 3 evidence will assist in infant/toddler rehabilitation decision-making.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03910075.

Background: Despite antiplatelet therapy, plaque-induced strokes recur frequently. This recurrence may reflect thrombus heterogeneity driven by peri-stenotic stagnation and red blood cell (RBC) entrapment. The clinical implications of such variations for stroke outcomes remain unclear. We investigated whether plaque-derived RBC-rich thrombi, indicated by the clot sign, were associated with recurrence, lesion volume, and stenosis-related hemodynamics.

Methods: Because asymptomatic plaque rupture limits direct evaluation of hemodynamics and thrombus compositions, we performed a hybrid human-animal study. In humans, we conducted a retrospective case-control study across 2 tertiary stroke centers in the Republic of Korea between April 2017 and March 2024, evaluating stroke recurrence and lesion volume by clot sign, using inverse probability of treatment weighting. We included artery-to-artery embolization confirmed by diffusion weighted imaging, excluding other etiologies. In animals, thrombus compositions were histologically analyzed in an FeCl₃-induced stenosis model across 3 segments (ascent, peak, and descent). Peri-stenotic hemodynamics, including wall shear stress and relative residence time, were assessed using ultrafast ultrasound imaging to evaluate whether RBC entrapment correlated with elevated relative residence time.

Results: In humans, clot sign-positive patients exhibited higher recurrence risk (hazard ratio, 2.76 [95% CI, 1.32-5.74]; P=0.007), and larger lesion (mean difference, 16.14 [95% CI, 5.03-27.25]; P=0.005). In animals, RBCs proportion was increased in the descent (ascent, 23.89±15.91%; peak, 12.33±11.19%; descent, 59.58±35.09%; P=0.019), correlating with a 3-fold higher relative residence time in the descent than the other regions (ascent, 1.25±0.75 au; peak, 1.55±0.55 au; descent, 4.50±2.74 au; P=0.001).

Conclusions: Peri-stenotic stagnation was associated with RBC-rich thrombi formation under both clinical and experimental conditions, providing mechanistic insight into stroke recurrence and larger lesion volumes. Identifying peri-stenotic stagnation using ultrafast ultrasound imaging may help stratify high-risk patients; however, its therapeutic implications require validation in prospective randomized studies.

Ischemic stroke is a major global health burden, leading to considerable mortality and long-term disability. Endovascular thrombectomy and mechanical recanalization have revolutionized acute stroke care. Nonetheless, many patients experience poor long-term neurological outcomes, which are often attributed to the no-reflow phenomenon and activation of inflammatory cascades. The perioperative period of endovascular thrombectomy, managed under either general anesthesia or conscious sedation, represents a critical window where anesthetic strategies may influence recovery through hemodynamic control and possibly immune modulation. This consensus review was generated by an international multidisciplinary expert group and synthesizes preclinical and clinical evidence to evaluate the promise of various immunomodulatory strategies for improving functional outcomes in patients with ischemic stroke following endovascular thrombectomy. Our goal is to provide a foundational reference for future research and development of novel perioperative immune therapies for patients with endovascular thrombectomy.

About 10% to 15% of patients with ischemic stroke have a history of cancer, half of whom have active malignancy at the time of stroke. With improved cancer treatments extending patient survival, the coprevalence of these diseases has increased steadily since 2000. This has sparked considerable growth in research and knowledge on this topic. Approximately half of ischemic strokes in patients with active cancer are due to conventional mechanisms, although cancer-related factors may contribute. The remaining half of ischemic strokes in this population are typically classified as cryptogenic or attributed to cancer-specific mechanisms. These cryptogenic strokes often have characteristic risk markers and clinical features and are extremely high risk for recurrent stroke and other adverse events, distinguishing them from other stroke subgroups. Recent epidemiological, translational, and histopathological data indicate that many of these events are likely caused by the cancer itself through multifactorial prothrombotic processes. In this scientific statement incorporating multidisciplinary expertise, we critically appraise and synthesize recent evidence and provide clinical suggestions on the epidemiology, presentation, evaluation, pathophysiology, and treatments for ischemic stroke in patients with active cancer. In addition, we propose a novel classification for ischemic stroke attributed to cancer itself, which we define as cancer-related stroke to enable consistent nomenclature and to harmonize stroke classification across clinical practice and research. This system is based on routinely available clinical data and includes different categories for certainty of causality, relating to the patient's distinctive clinical features and estimated risk for recurrent thromboembolism. We hope this framework spurs dedicated controlled trials to address areas of clinical uncertainty.

Background: Maternal stroke is an uncommon but serious complication of pregnancy. This study assessed the incidence, temporal trends, and outcomes of maternal stroke in the United States using the Cosmos Epic database.

Methods: We conducted a retrospective analysis of pregnancies resulting in births between January 1, 2016, and January 1, 2024, using the Cosmos Epic database, which includes deidentified electronic health records from >1800 US hospitals and 41 500 clinics. Maternal stroke was defined as any inpatient admission with a stroke diagnosis during pregnancy or within 6 weeks postpartum. The primary outcome was maternal stroke incidence; secondary outcomes included maternal mortality, delivery complications, and neonatal outcomes. Propensity score matching (1:1) was applied to adjust for confounding.

Results: Among 5 404 933 pregnancies, 2637 were complicated by stroke, yielding an incidence of 48.8 per 100 000 pregnancies. Ischemic stroke was most common (52.6%), followed by hemorrhagic stroke (40.7%). The overall rate remained stable though ischemic stroke showed an upward trend. Women with stroke were older and more likely to be Black, and had higher rates of hypertension, dyslipidemia, congenital heart disease, and eclampsia. In the matched cohort (n=1200 pairs), the stroke group had higher mortality (1.7% versus 0%), more delivery complications, lower birth weight, and longer neonatal hospital stays. Among 409 subsequent pregnancies, recurrent stroke occurred in 14.7% but with no maternal mortality and favorable neonatal outcomes.

Conclusions: Maternal stroke, though rare, carries substantial risks. The increasing ischemic stroke trend warrants targeted prevention and multidisciplinary perinatal management.

Background: The utility of 24- to 48-hour follow-up infarct volume (FIV) as a surrogate outcome in late time-window acute ischemic stroke is unclear. We aimed to determine associations of 24- to 48-hour FIV and clinical outcome in patients presenting >6 hours from last known well with and without endovascular treatment (EVT).

Methods: Post hoc analysis of the AURORA (Thrombectomy for Anterior Circulation Stroke Beyond 6 h From Time Last Known Well) patient-level meta-analysis of 6 randomized trials of late-window EVT. Patients were randomized to EVT or the control arm (best medical care). FIV was assessed on follow-up computed tomography or magnetic resonance imaging at 24 to 48 hours. Multivariable binary logistic regression with adjustment for key covariates was performed to estimate probabilities of achieving functional independence (modified Rankin Scale [mRS] score, 0-2 at 90 days) based on FIV. Mediation analysis was performed to determine the proportion of the EVT effect that is explained by FIV reduction.

Results: Four hundred forty-nine patients of 505 patients (88.9%) had available FIV and 90-day mRS and were included. Patients with worse outcomes at 90 days had larger FIV (median FIV in 90-day mRS score, 1:13.7 mL [interquartile range, 6.1-31.3] versus mRS score, 6:59.6 [18.8-145.0]; P<0.01). In the EVT arm, the estimated probability of achieving an mRS score of 0 to 2 declined with increasing FIV, from 65% at 0 mL FIV to 4% at 200 mL. In the control arm, this association was weaker, and the mRS score of 0 to 2 probabilities were overall lower. Only 5.9% of EVT's effect on clinical outcome was explained by FIV reduction.

Conclusions: FIV mediated only a small proportion of the EVT effect on clinical outcome, and the association of FIV and outcomes was much weaker; overall outcomes were worse in the control arm compared with the EVT arm. For FIV up to 100 mL, EVT results in substantially better clinical outcomes than best medical management given the same FIV. The utility of FIV as a surrogate outcome in late time-window stroke may be limited.

Background: Evidence-based practice relies on clinical guidelines, whose recommendations depend on the quality, relevance, and validity of supporting research. We evaluated the class/strength and level of evidence (LOE) or quality of evidence (QOE) supporting American Heart Association/American Stroke Association and European Stroke Organisation guideline recommendations, and examined temporal changes in LOE.

Methods: Stroke guidelines from American Heart Association/American Stroke Association (1995-2025) and European Stroke Organisation (2014-2025) were identified through society websites and EMBASE/MEDLINE. Eligible documents contained recommendations with class/strength and LOE/QOE. Consensus statements were excluded. Since 2006, American Heart Association/American Stroke Association has classified LOE as A (multiple or large randomized-controlled trials), B (single trial or observational studies), or C (expert opinion). European Stroke Organisation applies the Grading of Recommendations Assessment, Development, and Evaluation system (high, moderate, low, and very low QOE).

Results: Across 1102 recommendations in 9 current American Heart Association/American Stroke Association stroke guidelines, 156 (14.2%) were supported by LOE A, 559 (50.7%) by LOE B, and 387 (35.1%) by LOE C. Of 407 class I recommendations (ie, should do), and 117 class III recommendations (ie, should not do), 116 (22.1%), 258 (49.2%), and 150 (28.6%) were supported by LOE A, B, and C, respectively. Although the number of recommendations increased across guideline updates (median, 22 [interquartile range, 25th-75th percentiles, 18.0-42.0]), the proportion supported by LOE A declined (median, -4.6% [interquartile range, -7.8 to -0.8]). Across 260 recommendations in 30 European Stroke Organisation guidelines, 19 (7.3%) were supported by high, 62 (23.8%) by moderate, 81 (31.2%) by low, and 98 (37.7%) by very low QOE. Among 90 strong recommendations, 18 (20.0%) were supported by high QOE, and 66.7% of guideline topics had no recommendations supported by high QOE. There was insufficient evidence to make recommendations for 123 (32.7%) clinical questions.

Conclusions: Due to limited randomized data for many important clinical questions, most stroke guideline recommendations are based on low-to-moderate-quality evidence. These findings emphasize the need to improve the funding, design, and delivery of efficient, patient-focused clinical trials.

Background: The non-immunogenic staphylokinase is a recombinant staphylokinase with low immunogenicity, high thrombolytic activity, and fibrin selectivity approved in Russia for the acute ischemic stroke (AIS) thrombolytic therapy within 4.5 hours after symptom onset. We evaluated safety and efficacy outcomes of the non-immunogenic staphylokinase usage in patients with AIS in the Fortelyzin Population Investigation registry.

Methods: Between March 2021 and October 2024, patients with AIS treated with the non-immunogenic staphylokinase were enrolled in the prospective, open-label, internet-based, monitored, observational Fortelyzin Population Investigation registry. Demographics, risk factors, baseline stroke severity (defined by National Institutes of Health Stroke Scale), and onset to treatment time were recorded. Safety outcomes included symptomatic intracerebral hemorrhage (according to the ECASS III [European Cooperative Acute Stroke Study III] and SITS-MOST [Safe Implementation of Thrombolysis in Stroke-Monitoring Study] criteria) within 36 hours and all-cause mortality on day 90. Efficacy outcome was evaluated by functional independence using of modified Rankin Scale score of 0 to 2 on day 90.

Results: A total of 17 636 patients with AIS were treated with the non-immunogenic staphylokinase in 329 centers participated in the Fortelyzin Population Investigation registry during the study period (median age 68 [60-75]; 56% male; median baseline National Institutes of Health Stroke Scale score, 11 [8-16] points; median onset to treatment time, 2.4 hours [1.8-3.1]). The rate of symptomatic intracerebral hemorrhage according to the ECASS III criteria was 2% (356/17 636; 1.8-2.2), to the SITS-MOST criteria, 2% (330/17 636; 1.8-2.1). All-cause mortality on day 90 was 9% (1588/17 636; 8.6-9.4). The number of patients with a modified Rankin Scale score of 0 to 2 on day 90 was 61% (10 799/17 636; 60.5-61.9). These safety and efficacy outcomes were comparable with FRIDA (Fortelyzin Randomized Investigation Compared With Alteplase) randomized clinical trial results.

Conclusions: The presented data suggest that intravenous thrombolysis with the non-immunogenic staphylokinase is safe and effective in routine clinical practice when used within 4.5 hours of AIS symptoms onset. These findings should encourage the wider usage of thrombolytic therapy with the non-immunogenic staphylokinase for suitable patients.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT06707987.