WAKE-UP study a wake-up call for acute stroke care

Some solutions are simple, though not necessarily obvious. The WAKE-UP study, which included 70 participating European stroke centers, has now studied a relatively simple procedure to manage the acute care of stroke patients and avoid potential long-term effects. Best of all, it is available wherever MRI is offered.

In this MEDICA-tradefair.com interview, Prof. Götz Thomalla talks about the use of thrombolysis to treat acute stroke, explains how two different MRI sequences can effectively improve the treatment and reveals what this means for the guidelines in acute treatment.

Prof. Thomalla, what was the reason behind the WAKE-UP study?

Prof. Götz Thomalla: Patients who have had a stroke with unknown time of onset – patients who go to sleep and awaken with stroke symptoms for example – have so far been excluded from acute thrombolytic treatment for stroke, that being a treatment that opens blocked blood vessels to dissolve a blood clot. Currently, thrombolysis is still the only approved and recommended treatment within 4.5 hours of stroke onset since it becomes less effective if carried out after this time window and it involves a slight risk of bleeding.

In the study, we researched whether these patients can be effectively and safely treated using MRI scans to detect and diagnose recent stroke, even if the actual time of symptom onset is unknown. This would subsequently also render an effective treatment option for this group of patients. After all, this would affect one in five stroke patients and could prevent long-term neurological complications or impairments.

What types of MRI exams did you perform on the patients?

Thomalla: The first exam is the diffusion-weighted imaging technique or DWI. It safely and very accurately indicates a probable stroke within a few minutes after the onset of restricted blood flow, so that we were able to clearly show that the patient has had a stroke and identify the location of the disturbance.

The second exam involves the "fluid-attenuated inversion recovery" (FLAIR) MRI sequence, which indicates edema in tissue, the accumulation of water. This edema does not appear until several hours after stroke onset.

The mismatch between the two sequences – when we see a definitive stroke via DWI, but no distinct changes in the FLAIR sequence yet – tells us that the stroke onset was less than four or five hours ago. This means the patient is very likely still within the treatment window where he/she can benefit from thrombolysis.

Thomalla: That is a great question and we wondered the same thing. DWI and FLAIR are common sequences that are readily available in MRI diagnostics. They do not take long and do not require complicated post-processing or assessment. You simply have to view them from a “stroke” perspective.

The main reason for using imaging during the acute phase of stroke is always to clinically differentiate cerebral hemorrhage from ischemic stroke, a disturbed blood flow due to vascular occlusion. A CT scan can show this quite well, which has become the standard test in this instance, and ensures that a patient with hemorrhagic stroke is not mistakenly treated with anticoagulant thrombolytic therapy. Patients with an unknown time of symptom onset have so far not been researched and considered in studies. Perhaps the view has been that they cannot be effectively treated at that moment without running the risks of thrombolysis.

Nine years ago, we already published our idea to use the deviation between DWI and FLAIR sequences for analysis. A number of research papers have reviewed our findings, but there had not been a major clinical trial that illustrated that this concept can also be used to effectively manage the treatment and lead to a better outcome.

How will your findings change the way acute stroke is being treated?

Thomalla: In order to achieve a comprehensive use in clinical practice, national and international guidelines must incorporate our findings. The concept already became known during the study and now a number of centers have already integrated it into their routine practice. Many centers told us they implement the concept because they feel very confident about it. We use it in clinical routine practice as well.

Over the past three or four years, we have seen dramatic improvements in stroke treatment thanks to thrombectomy, a procedure that involves the removal of occlusive thrombi (blood clots) with a catheter. This is a vast improvement, especially for patients affected by a blocked large artery in the brain.

Our treatment approach is a wonderful addition to this. After all, in clinical practice patients are being treated with either thrombolysis or thrombolysis and thrombectomy. Now our study findings will benefit a patient population that is moderately or even just mildly affected and that would not be considered candidates for thrombectomy.

What other research questions are you going to review as part of the WAKE-UP study?

Thomalla: We want to study if and how we can better manage the treatment by further evaluating whether certain patient subgroups benefit at a higher degree or whether there are subgroups that do not benefit at all or are even at increased risk.

Another question pertains to CT diagnostics. Unlike an MRI procedure, it is more commonly used in clinical practice. Even though a percentage of the changes we detect via an MRI can also be seen on a CT scan, we cannot actually see all of them. That’s why we need to study whether similar results can also be achieved with CT scans. For many centers, our findings will definitely translate into changing guidelines since CT diagnostics has seen an increased use during the acute phase in recent years. Generally, a CT angiography is usually effective to determine thrombectomy treatment in stroke. Our study now provides data that clearly shows that patients with an unknown time of stroke onset should primarily undergo an MRI scan.