Barbagallo M, Zahn M, Zimmermann J, Klövekorn R, Held J, Nemeth B, Reolon B, Bellomo J, Schwarz A, Veerbeek J M, Van Niftrik C H B, Sebök M, Piccirelli M, Michels L, Luft A R, Kulcsar Z, Regli L, Esposito G, Fierstra J, Thurner P, Schubert T, Wegener S
Department of Neurology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Clinical Neuroscience Center, University of Zurich, Zurich, Switzerland.
Front Neurol. 2025 Aug 22;16:1639880. doi: 10.3389/fneur.2025.1639880. eCollection 2025.
Reperfusion failure (RF) describes a condition in which patients suffering a large vessel occlusion (LVO) stroke present insufficient tissue reperfusion and recovery despite optimal mechanical thrombectomy (MT) results. Approximately 50% of patients suffering from LVO are affected. Our current understanding of the underlying pathomechanisms is limited and mostly based on rodent models. The goal of this study was to further characterize RF by applying advanced multimodal hemodynamic imaging in stroke patients.
Patients from the IMPreST study with LVO stroke and successful recanalization [corresponding to thrombolysis in cerebral ischemia grade (TICI) 2b-3] were included. Follow-ups with blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) and non-invasive optimal vessel analysis (NOVA) imaging were performed (<72 h, 7 days and 90 days). Demographic and clinical data (NIHSS and mRS) were collected.
Of the 49 patients included in IMPreST, 18 patients met the inclusion criteria. Based on the perfusion weighted imaging (PWI) of the affected area compared to the contralateral side after MT, patients were stratified into three groups: hypoperfusion ( = 3), normalization ( = 8), and hyperperfusion ( = 7). The hyperperfusion group tended to show poorest clinical outcome (mRS 3 months: 2.5 [Q1-Q3 2.0-3.0] vs. normalization: 1 [Q1-Q3 0.75-3.0], = 0.169) and had significantly lower BOLD-CVR values at visit one and two compared to hypoperfusion and normalization groups, indicating impaired cerebrovascular reactivity (visit1 hyperperfusion group -0.01 [Q1-Q3-0.02 - 0.07], normalization group 0.12 [0.09, 0.19], hypoperfusion group, 0.09 [0.09, 0.11] = 0.049, visit2 hyperperfusion group 0.07 [Q1-Q3 0.03-0.10], normalization group 0.17 [0.16, 0.18], hypoperfusion group 0.10 [0.09, 0.11], = 0.014).
We found three patterns of reperfusion after successful MT of LVO stroke: normalization, hypo- and hyperperfusion of the ischemic area on days at < 72 h after stroke. There was substantial inhomogeneity in perfusion and clinical outcomes between the three groups. Next to poorest clinical outcome, the hyperperfusion-group showed poorest cerebrovascular reserve, reflecting findings of RF in rodent models. Thus, we suggest that RF includes both hypo- as well as hyperperfusion. Early detection using advanced imaging would allow a better identification of patients at risk for poor clinical outcome.
http://clinicaltrials.gov, Identifier (NCT04035746).
再灌注失败（RF）是指尽管进行了最佳机械取栓（MT），但患有大血管闭塞（LVO）性卒中的患者仍存在组织再灌注不足和恢复不佳的情况。约50%的LVO患者受其影响。我们目前对其潜在病理机制的理解有限，且大多基于啮齿动物模型。本研究的目的是通过对卒中患者应用先进的多模态血流动力学成像进一步表征RF。
纳入来自IMPreST研究的LVO性卒中和成功再通[相当于脑缺血溶栓分级（TICI）2b - 3级]的患者。进行血氧水平依赖性功能磁共振脑血管反应性（BOLD - CVR）和无创最佳血管分析（NOVA）成像随访（<72小时、7天和90天）。收集人口统计学和临床数据（美国国立卫生研究院卒中量表[NIHSS]和改良Rankin量表[mRS]）。
在IMPreST纳入的49例患者中，18例符合纳入标准。根据MT后患侧与对侧的灌注加权成像（PWI）结果，将患者分为三组：灌注不足组（n = 3）、灌注正常组（n = 8）和灌注过度组（n = 7）。灌注过度组的临床结局往往最差（3个月时mRS：2.5[四分位间距（Q1 - Q3）2.0 - 3.0]，而灌注正常组为1[Q1 - Q3 0.75 - 3.0]，P = 0.169）；与灌注不足组和灌注正常组相比，灌注过度组在首次和第二次随访时的BOLD - CVR值显著更低，表明脑血管反应性受损（首次随访时，灌注过度组为 - 0.01[Q1 - Q3 - 0.02 - 0.07]，灌注正常组为0.12[0.09，0.19]，灌注不足组为0.09[0.09，0.11]，P = 0.049；第二次随访时，灌注过度组为0.07[Q1 - Q3 0.03 - 0.10]，灌注正常组为0.17[0.16，0.18]，灌注不足组为0.10[0.09，0.11]，P = 0.014）。
我们发现LVO性卒中成功MT后存在三种再灌注模式：卒中后<72小时内缺血区域的灌注正常、灌注不足和灌注过度。三组之间的灌注和临床结局存在显著异质性。除了最差的临床结局外，灌注过度组还表现出最差的脑血管储备，这与啮齿动物模型中RF的研究结果一致。因此，我们认为RF包括灌注不足和灌注过度。使用先进成像技术进行早期检测将有助于更好地识别临床结局不佳风险的患者。
