Dipartimento di Scienze dell'Invecchiamento, Neurologiche, Ortopediche e della Testa-Collo, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
Catholic University of Sacred Heart, Rome, Italy.
J Neurol Sci. 2022 May 15;436:120206. doi: 10.1016/j.jns.2022.120206. Epub 2022 Feb 23.
Cerebral edema (CED) is a common complication of ischemic stroke in Intensive Care Unit. Although frequently observed in patients undergoing intravenous thrombolytic (IVT) treatment, the pathogenic role of recombinant tissue plasminogen activator (rtPA) in CED induction has not yet been definitively clarified. The aim of our study is to verify the relationship between CED and rtPA in patients affected by acute ischemic stroke, without reperfusion signs, evaluating the CED growth rate in the first week after stroke onset. In this single-center, retrospective observational study, we included all consecutive patients with acute stroke undergone multi-parameter monitoring of vital signs in the sub-intensive care Unit. We included both patients undergoing systemic IVT and standard medical treatment (n-IVT) with the following time of CT scan: within 4.5 h onset, 24 ± 12 h, 72 ± 24 h and 120 ± 24 h from the stroke onset. Of 1753 with acute ischemic stroke patients screened, 810 patients were included in the study (218 IVT and 592 n-IVT). No significant difference was observed at baseline in age, gender, NIHSS score or infarcted area, while hemorrhagic transformation rate was significantly higher in IVT than in n-IVT group. We observed a significant increase of CED growth rate in IVT patients compared to n-IVT patients only between 24 and 72 h from the ischemic event (respectively 1.85cm/h and 0.89cm/h; p = 0.031) regardless of the presence of HT. No significant difference was observed in growth rate between 3 and 5 days following rtPA administration or in overall growth rate. Although the pathogenetic mechanism of rtPA determining CED remains uncertain, our data suggests rtPA can act as a "trigger" of edema onset and progression. Therefore, drugs interfering with specific molecular pathways, such as kallikrein-kinin cascade, could constitute an effective strategy to reduce the risk of development and progression of rtPA-related cerebral edema in patients with acute stroke. Further studies are needed to define the molecular pathways involved in the genesis of CE in humans and to verify the efficacy of specific drugs.
脑水肿（CED）是重症监护病房中缺血性脑卒中的常见并发症。尽管在接受静脉溶栓（IVT）治疗的患者中经常观察到，但重组组织纤溶酶原激活剂（rtPA）在 CED 诱导中的致病作用尚未得到明确阐明。我们的研究旨在验证急性缺血性脑卒中患者中 CED 与 rtPA 之间的关系，这些患者没有再灌注迹象，评估脑卒中发病后第一周 CED 的增长率。在这项单中心、回顾性观察性研究中，我们纳入了所有在亚重症监护病房接受生命体征多参数监测的急性脑卒中连续患者。我们纳入了接受全身 IVT 和标准药物治疗的患者（n-IVT），并在以下时间进行 CT 扫描：发病后 4.5 小时内、24 ± 12 小时、72 ± 24 小时和 120 ± 24 小时。在筛选出的 1753 例急性缺血性脑卒中患者中，810 例患者纳入了研究（218 例 IVT 和 592 例 n-IVT）。在基线时，年龄、性别、NIHSS 评分或梗死面积无显著差异，而 IVT 组的出血转化发生率显著高于 n-IVT 组。我们观察到，与 n-IVT 患者相比，仅在缺血事件后 24 至 72 小时之间，IVT 患者的 CED 增长率显著增加（分别为 1.85cm/h 和 0.89cm/h；p=0.031），无论是否存在 HT。在 rtPA 给药后 3 至 5 天或总体增长率方面，增长率无显著差异。尽管 rtPA 确定 CED 的发病机制尚不确定，但我们的数据表明 rtPA 可以作为水肿发作和进展的“触发因素”。因此，干扰特定分子途径的药物，如激肽释放酶-激肽系统，可能是减少急性脑卒中患者 rtPA 相关脑水肿发生和进展风险的有效策略。需要进一步研究以确定人类 CED 发病的分子途径，并验证特定药物的疗效。
