European Stroke Organisation Conference
May 22–24, 2019
Lina Palaiodimou, MD
In general, this year’s European Stroke Organisation Conference was characterized by the presentation of numerous clinical dilemmas and highlighted the need for new research targeted to their resolution, which is most likely to be found on the ground of personalized medicine. The session “Future Directions on Thrombolysis” provided some insight about subjects regarding management of acute ischemic stroke that have perpetually troubled clinicians during everyday practice.
The first talk, by William Whiteley, confirmed safety and efficacy of intravenous thrombolysis using data from the analysis of pooled stroke thrombolysis trials. Specifically, it was confirmed that the proportional benefits of alteplase increase with earlier treatment, and this association is independent of age and stroke severity. There is, of course, an increased risk of death from intracerebral hemorrhage (ICH) in the alteplase treated patients, but there is no significant effect on other causes of early or later death. Among those patients treated earlier, there is a suggestion that the early hazard due to death from ICH may be compensated by a later benefit regarding death from any cause within 90 days. Whiteley finally concluded, presenting a well-intelligible graph, that the absolute balance of benefit versus risk depends chiefly on treatment delay and stroke severity.
Ewgenia Barow gave the second talk, titled “Thrombolysis in lacunar stroke (including results from the MRI-based randomized controlled WAKE-UP trial)”. No specific recommendations about lacunar stroke acute treatment exist in guidelines, and this has been a longstanding clinical dilemma. The main concern about thrombolysis in lacunar stroke is the vascular pathology itself, which was considered to be unsusceptible to thrombolysis and even more prone to ICH. These considerations with the addition of the generally low scores of NIHSS and the rapid recovery and favorable prognosis in lacunar strokes led to withholding acute reperfusion treatment in those patients by many clinicians. Barow presented a secondary analysis of the WAKE-UP trial with the aim to explore safety and efficacy of intravenous thrombolysis in patients with lacunar infarcts. Regarding efficacy, it was shown that treatment with alteplase is associated with higher odds of favorable outcome (mRS score 0-1) at 90 days and with a favorable shift towards better functional outcome at 90 days after stroke as well. On the other hand, rates of mortality and ICH are low. Of special interest is the fact that among patients with lacunar strokes enrolled in the WAKE-UP trial, 8% also had concurrent embolic infracts, so, as Barow suggested, the lacunar pathophysiological hypothesis should be challenged, and possible embolic mechanisms should be assessed. The above presentation by Barow gave enough evidence that intravenous thrombolysis should not be withheld in patients with lacunar infarcts.
“Off-label thrombolysis in acute ischemic stroke” by Niaz Ahmed was the third talk. Ahmed presented a series of contraindications to thrombolysis and showed evidence of how they can be overcome. First of all, the time limit of 4.5 hours, which used to be an absolute threshold, is now outdated due to strong evidence provided by WAKE-UP and the EXTEND trial. Of course, this approach is personalized and based on imaging criteria. Clinicians may also withhold thrombolysis in patients with low NIHSS scores, but it was actually shown that minor-stroke patients treated with alteplase have higher odds of favorable outcome. Regarding high NIHSS scores, stroke patients with NIHSS ≥ 22 also have higher odds of favorable outcome when treated with alteplase than controls, based on observational data. Other usual contraindications were also discussed, such as previous stroke <3 months and history of diabetes mellitus and stroke, and observational data also showed that alteplase is safe and effective compared to control. Previous anticoagulation treatment as a contraindication for thrombolysis was also assessed, and Ahmed pointed out that observational studies provide good safety data, but recommendations regarding the time point of last dose taken are lacking.
Georgios Tsivgoulis provided a lecture about thrombolysis and cerebral microbleeds, the presence of which have troubled many clinicians regarding alteplase treatment. Tsivgoulis stressed that the risk of symptomatic ICH after intravenous thrombolysis is higher when there is a high cerebral microbleed burden, that is more than 10, based on different meta-analyses and prospective observational studies as well. The most probable pathophysiological mechanism is that high cerebral microbleeds burden actually reflect arteriolar injury, which in turn permits the extravasation of blood. Strict control of blood pressure before, during and after thrombolysis in these cases is of upmost importance. All things considered, in otherwise eligible patients who had a previously demonstrated small number (1-10) of cortical microbleeds on MRI, administration of IV alteplase is reasonable, according to the recent American Heart Association/American Stroke Association recommendations. Recent data were also provided about the occurrence of new cerebral microbleeds in patients that received thrombolysis for previous stroke. Finally, Tsivgoulis drew the attention to cases of absolute contraindications for thrombolysis that can be associated with microbleeds on MRI; those were infective endocarditis and aortic dissection.
Sanne Zinkstok gave the final talk about thrombolysis in stroke mimics. Following the motto “time is brain” and reducing door-to-needle time resulted inevitably in thrombolysing more cases of stroke mimics. However, safety is not an issue in those cases; costs are. For that reason, Zinkstok suggested the use of different stroke mimic predictors, such as the “FABS” score and “TeleStroke Mimic Scores” and stated that CT-perfusion might be helpful as well, despite the presence of certain pitfalls of this imaging method that should be kept in mind.
The “Future Directions on Thrombolysis” session provided important data regarding certain groups of acute ischemic stroke patients and clinical scenarios that have tormented most clinicians at some point. Considering these directions can give the opportunity to overcome some previous contraindications for thrombolysis in patients fulfilling certain clinical and radiological criteria, and result in better clinical outcomes of stroke survivors.