Ischaemic strokes have traditionally been classified according to the TOAST criteria, in which strokes with unclear aetiology are classified as cryptogenic strokes. However, the definition of cryptogenic stroke did not meet the operational criteria necessary to define patient populations for randomized treatment trials. To address this problem, the concept of embolic stroke of undetermined source (ESUS) was developed and published in 2014. A hypothesis that underpinned this concept was that most strokes in patients with ESUS are caused by embolic events, perhaps many cardioembolic, and that anticoagulation would prevent secondary ischaemic events. On this basis, two large randomized trials were conducted to compare the non-vitamin K antagonist oral anticoagulants (NOACs) dabigatran and rivaroxaban with aspirin. Neither NOAC was superior to aspirin in these trials, although subgroups of patients with ESUS seemed to benefit specifically from anticoagulation or antiplatelet therapy. The neutral results of the trials of anticoagulation and insights into ESUS from research conducted since the concept was introduced warrant reassessment of the ESUS construct as a research concept and a treatment target. In this Review, we discuss the evidence produced since the concept of ESUS was introduced, and propose updates to the criteria and diagnostic algorithm in light of the latest knowledge.

传统上，缺血性中风根据 TOAST 标准进行分类，其中病因不明的中风被归类为隐源性中风。然而，隐源性卒中的定义不符合为随机治疗试验定义患者人群所必需的操作标准。为了解决这个问题，2014 年提出并发表了来源不明的栓塞性卒中 (ESUS) 的概念。支持这一概念的假设是，大多数 ESUS 患者的卒中是由栓塞事件引起的，可能很多是心源性栓塞，并且抗凝治疗将防止继发性缺血事件。在此基础上，进行了两项大型随机试验，比较非维生素 K 拮抗剂口服抗凝药 (NOAC) 达比加群和利伐沙班与阿司匹林的疗效。在这些试验中，NOAC 均不优于阿司匹林，尽管 ESUS 患者亚组似乎特别受益于抗凝或抗血小板治疗。抗凝试验的中立结果和自引入概念以来进行的研究对 ESUS 的见解保证了对 ESUS 结构作为研究概念和治疗目标的重新评估。在这篇综述中，我们讨论了自引入 ESUS 概念以来产生的证据，并根据最新知识提出了对标准和诊断算法的更新。抗凝试验的中立结果和自引入概念以来进行的研究对 ESUS 的见解保证了对 ESUS 结构作为研究概念和治疗目标的重新评估。在这篇综述中，我们讨论了自引入 ESUS 概念以来产生的证据，并根据最新知识提出了对标准和诊断算法的更新。抗凝试验的中立结果和自引入概念以来进行的研究对 ESUS 的见解保证了对 ESUS 结构作为研究概念和治疗目标的重新评估。在这篇综述中，我们讨论了自引入 ESUS 概念以来产生的证据，并根据最新知识提出了对标准和诊断算法的更新。