Thrombolysis with recombinant tissue plasminogen activator in acute ischemic stroke aims to restore compromised blood flow and prevent further neuronal damage. Despite the proven clinical efficacy of this treatment, little is known about the short-term effects of systemic thrombolysis on structural brain connectivity. In this secondary analysis of the WAKE-UP trial, we used MRI-derived measures of infarct size and estimated structural network disruption to establish that thrombolysis is associated not only with less infarct growth, but also with reduced loss of large-scale connectivity between grey-matter areas after stroke. In a causal mediation analysis, infarct growth mediated a non-significant 8.3% (CI_95% [−8.0, 32.6]%) of the clinical effect of thrombolysis on functional outcome. The proportion mediated jointly through infarct growth and change of structural connectivity, especially in the border zone around the infarct core, however, was as high as 33.4% (CI_95% [8.8, 77.4]%). Preservation of structural connectivity is thus an important determinant of treatment success and favourable functional outcome in addition to lesion volume. It might, in the future, serve as an imaging endpoint in clinical trials or as a target for therapeutic interventions.

在急性缺血性中风中使用重组组织纤溶酶原激活剂进行溶栓旨在恢复受损的血流并防止进一步的神经元损伤。尽管这种治疗已被证明具有临床疗效，但对于全身性溶栓对结构性脑连接的短期影响知之甚少。在 WAKE-UP 试验的二次分析中，我们使用 MRI 衍生的梗死面积测量和估计的结构网络破坏来确定溶栓不仅与更少的梗死生长相关，而且与减少灰色之间的大规模连接损失有关。 - 中风后的重要区域。在因果中介分析中，梗塞生长介导了不显着的 8.3% (CI _95%[−8.0, 32.6]%) 溶栓对功能结果的临床影响。然而，通过梗塞生长和结构连接性变化共同介导的比例，特别是在梗塞核心周围的边界区域，高达 33.4% (CI _95% [8.8, 77.4]%)。因此，除了病变体积外，保持结构连接性是治疗成功和良好功能结果的重要决定因素。将来，它可能会作为临床试验中的成像终点或作为治疗干预的目标。