PhD defence V. (Vasiliki) Andreou-Chalos

Summary:

Ischemic stroke occurs when blood supply to a part of the brain is reduced or disrupted. It causes acute neurological deficits and results in high mortality and morbidity worldwide. In order to prevent irreversible damage of the brain tissue, patients should be treated as soon as possible to recover blood flow (‘time is brain’). For over two decades, intravenous thrombolysis (IVT) with alteplase had been the standard of care for all patients without contra-indications. In 2015, endovascular treatment (EVT) was proven effective and safe in patients with a large vessel occlusion of the anterior circulation. Although this resulted in a drastic improvement of functional outcome at group level, almost half of these patients do not recover to functional independence. Outcome prediction for individual patients remains challenging, as outcomes vary between patients and are based on multiple factors. Clinical prediction models combine multiple characteristics to estimate the probability of an outcome of interest for individual patients. They can be used by physicians to select which patients may benefit from EVT, but also to inform physicians, patients and their family members about the extent of recovery they can expect after EVT has been performed. In addition, it clearly recognized that EVT needs to be refined to further improve outcome. Optimizing macrovascular and microvascular reperfusion by modifying the pre-procedural intravenous alteplase and peri-procedural antithrombotic treatment strategies, could potentially improve outcomes. New evidence from clinical studies is needed to assess the potential benefit of these two approaches. This includes data from observational research, but ideally from randomized controlled trials (RCTs). Next to defining the primary objective of an RCT, important considerations in the design and execution of future RCTs regarding EVT include the selection of a primary outcome measure and the informed consent procedure.

The overall aim of the research presented in this thesis was to predict outcome of patients with ischemic stroke (Part I) and to find ways to further improve outcome of EVT by optimizing reperfusion (Part II) and by improving trial design and execution (Part III).