Reperfusion Injury after Endovascular Stroke Treatment

Stroke is a leading cause of death and disability worldwide. In Austria, around 25.000 people are affected by a stroke each year. In particular, stroke due to the occlusion of large vessels supplying the brain is associated with severe disability or even death. Fortunately, newly- developed treatment approaches have revolutionized the therapy of severe stroke in recent years. This new therapy is called mechanical thrombectomy and works as follows: via puncture of an artery in the groin region, a small catheter is directed to the brain circulation and to the occluded artery under radiological control. Afterwards, the blood clot that is occluding the vessel is removed either by aspiration or by using so called stent retrievers (=mechanical removal of the clot to restore the blood supply to the brain). While this treatment is technically highly effective 90% of vessel occlusions can be recanalized there are also some important complications that need to be considered after mechanical thrombectomy. The most important immediate complication is bleeding into brain, a situation that occurs in every 4th thrombectomy patient and that is related to an increased risk of poor neurological prognosis. The exact mechanisms why some patients develop brain hemorrhage after mechanical thrombectomy are still largely unclear. In first pilot studies, we and other research groups found that simple and complication-free ultrasound examinations of the brain arteries are helpful to predict the risk for brain bleeding after acute stroke treatment as patients who later developed brain hemorrhage had elevated blood flow velocities in the arteries that were just re-opened by mechanical thrombectomy (deleterious elevated blood circulation). In this Austrian multicenter study conducted in Graz, Innsbruck and Salzburg, we now aim to get further insights into the important complication of brain hemorrhage after endovascular stroke treatment. We will use serial ultrasound examinations of the brain arteries to study blood flow velocities and changes as well as novel MRI techniques to investigate brain tissue alterations related to blood flow changes. Furthermore, we intend to identify potential blood markers that might be associated with complications and prognosis after modern stroke treatment. Our overarching goal is to identify patients at risk for stroke complications and poor outcome, and in the long-term, to develop treatment approaches to avoid such complications.

In our research project, we investigated how cerebral blood flow changes after modern stroke treatment. The focus was on mechanical thrombectomy, a procedure in which blood clots are removed from blocked brain arteries in order to restore blood supply as quickly as possible. Over the past years, this treatment has revolutionized the care of patients with severe stroke. Nevertheless, some patients develop complications or recover less well than expected despite successful reopening of the vessel. The aim of our project was therefore to identify early warning signs for such complications. To achieve this, we examined more than 200 stroke patients using a specialized ultrasound technique ("transcranial duplex sonography") combined with advanced MRI perfusion imaging. Our results showed that, after successful reopening of a brain vessel, a temporary "hyperperfusion" - an excessive increase in blood flow - frequently occurs in the affected brain region. These changes could be detected directly at the patient's bedside using ultrasound. Importantly, we demonstrated that the ultrasound findings correlated very well with the considerably more complex MRI examinations. This showed that ultrasound represents a simple, rapid, and reliable method for monitoring cerebral blood flow after stroke. Furthermore, patients with pronounced hyperperfusion more often developed larger brain infarcts, brain swelling, or intracranial bleeding and overall had a higher risk of unfavorable clinical outcome. The study therefore provides important evidence that not only successful reopening of the blocked vessel is crucial, but also the subsequent regulation of cerebral blood flow. The findings of our project contribute to improving the treatment of stroke patients. In the long term, ultrasound monitoring may help identify high-risk patients at an early stage and allow more individualized treatment strategies, such as blood pressure management or intensive care monitoring. This may help reduce complications and improve recovery after stroke. Further studies from this multicenter project (Medical Universities of Graz and Innsbruck as well as PMU Salzburg) focus on blood biomarkers for the prediction and early detection of stroke-related complications and will be published in the near future.