Stroke最新文献

Aim: The "2026 Guideline for the Early Management of Patients With AIS" replaces the "2018 Guidelines for the Early Management of Patients With AIS" and the 2019 update to reflect recent advances in evidence. This updated guideline is intended to provide a comprehensive, up-to-date, evidence-based set of recommendations, advising management from prehospital evaluation through acute treatment and early in-hospital management of complications and initiation of early secondary prevention measures. The intended audience includes prehospital care professionals, physicians, allied health professionals, and hospital administrators.

Methods: A search for literature derived from research principally involving human subjects, published in English since the last AIS guideline in 2018 and the 2019 update, and indexed in MEDLINE, PubMed, Cochrane Library, and other selected databases relevant to this guideline, was conducted between September and December 2024. Additional high impact studies and articles published through March 2025 were added later, where appropriate.

Structure: This guideline represents the most current and comprehensive evidence available in AIS care. Key updates include the incorporation of new evidence related to thrombolytic choice and eligibility, determination of eligibility for endovascular thrombectomy, and management of hyperglycemia and dysphagia; a focused consideration of the pediatric population; and modification of the approach to thrombolysis contraindications. Although this guideline reflects significant advances, it also highlights gaps in knowledge and underscores the urgent need for continued research to further refine and improve treatment strategies.

Background: Intermittent hypoxia (IH) preconditioning enhances brain resilience, thereby protecting against subsequent ischemic injury, yet its precise mechanisms remain elusive. We tested the novel hypothesis that peripheral paracrine mechanisms mediate IH-induced neuroprotection.

Methods: A total of 492 C57BL/6J mice were used: 434 young males (2-3 months), 29 young females (2-3 months), and 29 aged males (18 months). A 2-week IH regimen (13% O₂, 5-minute intervals, 10 cycles/d) was applied to generate IH-derived plasma (IHP). To test the hypothesis, IHP or normoxic plasma (100 μL/injection) was intravenously administered every 3 days (6 doses total) before distal middle cerebral artery occlusion. For therapeutic evaluation, plasma was administered daily for 3 days after distal middle cerebral artery occlusion or 60-minute transient MCAO, followed by additional doses every 3 days for 6 doses in long-term transient MCAO studies. Infarct volume and neurological deficits were primary outcomes. Candidate circulating mediators were identified via proteomics and validated by antibody-mediated depletion and recombinant protein supplementation. Blood-brain barrier integrity was further examined.

Results: Systemic IHP administration protected against acute brain injury after distal middle cerebral artery occlusion, reducing infarct volume and improving sensorimotor performance. Poststroke administration of IHP conferred acute and sustained neuroprotection in transient MCAO, but not distal middle cerebral artery occlusion, improving sensorimotor and cognitive recovery and reducing brain atrophy up to 4 weeks after stroke. Proteomic profiling identified 120 IH-upregulated plasma proteins, notably PF4 (platelet factor 4), a cytokine with potent neuroprotective properties. PF4 immunodepletion abolished IHP-induced neuroprotection, whereas recombinant PF4 replicated these benefits across sex and age. Furthermore, PF4 treatment protected against blood-brain barrier disruption after tMCAO, attenuating IgG extravasation and loss of endothelial expression of zonula occludens-1.

Conclusions: These findings identify PF4 as a key paracrine mediator of IH-induced neuroprotection and support the therapeutic potential of both IHP and PF4-based interventions for ischemic stroke.

Background: Stroke burden and structural inequities in stroke education among US Spanish-speaking Hispanic and Latino (SSHL) adults suggest a need for culturally appropriate education. Existing Spanish stroke recognition acronyms need to be evaluated among SSHL adults.

Methods: A 3-phase exploratory sequential design was used. To inform design of AHORA (Andar [Walk] or Alzar [Raise], Hablar [Talk], Ojos [Eyes], Rostro [Face], Ambos Brazos [Both Arms] or Activar [Activate]), PARA Stroke (Palabras [Words], Alzar [Raise], Rostro [Face], Avisar [Warn]), and RÁPIDO (Rostro Caído [Face Drooping], Alteración Del Equilibrio [Loss of Balance], Pérdida de Fuerza en el Brazo o Una Pierna [Loss of Strength in an Arm or Leg], Impedimento Visual [Visual Impairment], Dificultad PARA Stroke Hablar [Difficulty Speaking], Obtén Ayuda [Get Help]) before a randomized, parallel, 4-group prepost efficacy study involving 1105 SSHL participants (phase 3), interviews with health care professionals (n=15; phase 1) in May-June 2022 and focus groups with SSHL individuals (n=24; phase 2) were conducted in June-July 2022. Participants viewed a 1-minute video that included AHORA, PARA Stroke, RÁPIDO, or usual care (education without an acronym). Stroke knowledge and intent to contact 9-1-1 were examined pre- and 30 days post-video exposure via online questionnaires. Ordinal regression analyses were completed to determine acronym performances in improving stroke recognition, and binomial regression analyses were completed to determine increasing intention to call 9-1-1. Post hoc repeated measures ANOVA was used to determine if any acronym led to the greatest increase in intention to call 9-1-1.

Results: At 30 days post-video (n=367), odds of recognizing more stroke signs compared with usual care were given as follows: odds ratio, 0.87 (95% CI, 0.45-1.69; P=0.69), odds ratio, 0.54 (95% CI, 0.28-1.00; P=0.05), and odds ratio, 1.47 (95% CI, 0.73-2.99; P=0.28), and odds of increased intent to call 9-1-1 were given as follows: 1.18 (95% CI, 0.59-2.37; P=0.64), 0.95 (95% CI, 0.49-1.80; P=0.76), and 1.06 (95% CI, 0.54-2.06; P=0.84) for AHORA, PARA Stroke, and RÁPIDO, respectively. The acronyms had significant long-term positive effects on the intent to call 9-1-1 (F[1101]=251.457; P<0.001; MSE=41.321) although no significant differences were observed between the acronyms.

Conclusions: AHORA, PARA Stroke, and RÁPIDO performed comparably to usual care. Healthcare professionals and SSHL consumers preferred a Spanish-language acronym, specifically RÁPIDO and PARA Stroke, compared with an acronym translated verbatim from English to Spanish.

Background: Clinical scores indicating large vessel occlusion (LVO) in acute stroke patients could streamline triage of patients with suspected LVO to endovascular centers. GFAP (glial fibrillary acidic protein) is a promising blood biomarker for indicating intracerebral hemorrhage in acute stroke. This study evaluates whether positive LVO score results combined with a prehospital negative GFAP test (thereby excluding intracerebral hemorrhage) could improve the accuracy of LVO detection.

Methods: This retrospective diagnostic accuracy study (DETECT LVO) is based on the prospective DETECT study (2022-2024, tertiary care hospital RKH Klinikum Ludwigsburg, Germany), which evaluated the rapid intracerebral hemorrhage detection in acute stroke, measuring prehospital plasma GFAP levels on a point-of-care platform (i-STAT Alinity Abbott). For DETECT LVO 5, established LVO scores (Rapid Arterial Occlusion Evaluation, Field Assessment Stroke Triage for Emergency Destination, 3-Item Stroke Scale, Emergency Medical Stroke Assessment, Cincinnati Prehospital Stroke Scale) were retrospectively calculated from paramedic protocols. LVOs were diagnosed with CT-angiography as follows: occlusion of the internal carotid artery, middle cerebral artery, and basilar artery. Diagnostic accuracy for LVO detection was determined using the area under the curve, sensitivity, specificity, positive predictive values, and negative predictive values.

Results: Three hundred fifty-three patients suspected of acute stroke (ischemic stroke, n=258; intracerebral hemorrhage, n=76; stroke mimics, n=19) with a mean age of 74.6 years were included. One hundred one patients with ischemic stroke suffered from LVO (internal carotid artery=23.8%; middle cerebral artery=64.4%; and basilar artery=11.9%). Integrating GFAP to LVO scores significantly increased area under the curve (95% CI) for LVO detection (Field Assessment Stroke Triage for Emergency Destination, 0.859 [0.818-0.893] to 0.899 [0.862-0.928]; Rapid Arterial Occlusion Evaluation, 0.845 [0.802-0.880] to 0.892 [0.855-0.923]; 3-Item Stroke Scale, 0.788, [0.741-0.829] to 0.865 [0.824-0.898]; Emergency Medical Stroke Assessment, 0.840 [0.796-0.875] to 0.870 [0.830-0.910]; Cincinnati Prehospital Stroke Scale, 0.827 [0.784-0.865] to 0.862 [0.821-0.896]; P<0.001).

Conclusions: Integrating LVO scores combined with GFAP measurements into the prehospital work-up of patients with acute stroke improves diagnostic accuracy for LVO prediction. In the future, this could enable direct transfers of patients with suspected LVO to endovascular centers with reduced misdiagnosis rates. Independent replication in diverse prehospital cohorts is warranted to confirm these findings.

Background: Lp-PLA2 (lipoprotein-associated phospholipase A2) is a sensitive biomarker of vascular inflammation and atherosclerosis. This study evaluated the influence of Lp-PLA2 activity on the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin among patients with minor stroke or transient ischemic attack carrying CYP2C19 loss-of-function alleles.

Methods: The CHANCE-2 trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events-II) randomized 6412 patients with minor stroke or transient ischemic attack carrying CYP2C19 loss-of-function alleles to receive ticagrelor-aspirin or clopidogrel-aspirin. This subgroup study included patients with available baseline Lp-PLA2 activity measurements, stratified by the median value of 188.4 nmol/min per milliliter. The primary efficacy and safety outcomes were stroke recurrence and severe or moderate bleeding events within 90 days. Associations between treatment and outcomes were assessed using multivariable Cox proportional hazards models, adjusting for a history of hyperlipidemia.

Results: A total of 5919 patients were included (mean age, 64.4 years; 33.9% female). Among patients with low Lp-PLA2 activity, ticagrelor-aspirin reduced the 90-day risk of recurrent stroke compared with clopidogrel-aspirin (5.4% versus 7.4%; adjusted hazard ratio, 0.72 [95% CI, 0.54-0.97]). In patients with high Lp-PLA2 activity, no significant difference was observed (6.9% versus 8.2%; adjusted hazard ratio, 0.84 [95% CI, 0.65-1.09]). The P value was 0.45 for the treatment × Lp-PLA2 activity interaction effect on stroke recurrence. The risk of bleeding associated with ticagrelor-aspirin did not differ across Lp-PLA2 activity levels.

Conclusions: In patients with minor stroke or transient ischemic attack carrying CYP2C19 loss-of-function alleles, elevated Lp-PLA2 activity did not significantly modify the efficacy or safety of dual antiplatelet therapy. Further research is needed to clarify the potential role of Lp-PLA2 in guiding individualized treatment decisions.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04078737.