By: Anke Wouters, Rustam Al-Shahi Salman

ESO European Stroke Science Workshop 2023

Session 5: Too much, too young


Keynote Lecture: Stroke in the young: what are we missing?

Speaker: Frank-Erik De Leeuw, RadboudUMC

Professor De Leeuw, gave an excellent keynote lecture summarizing the missing aspects of stroke in the young. Stroke patients of 18-50y old were considered as young strokes. The increase in the incidence of more than 50% during the last years is very worrisome. In his talk, prof. De Leeuw summarized three key factors about young stroke that we are currently missing: Cryptogenic causes, prognosis and adverse events.

  • How can we find the unknown causes of these strokes in the young?

Data from the Odyssey study were shown in which 1322 young ischemic stroke patients were included between 2013 and 2017 in 17 centers in the Netherlands. Around 25-30% of these patients had a cryptogenic stroke according to the TOAST-classification. However, risk factors like high temperature, physical exercise, flu-like episodes… all increased the risk of having a cryptogenic stroke in those young patients. Furthermore, according to geographical data, patients living in rural areas were at a greater risk compared to those living in urban areas in the Netherlands. Cancer was another important risk factor that was addressed. In stroke patients, the excess risk of having cancer was higher in young patients compared to older stroke patients. Probably it is not useful to screen all young stroke patients for cancer but only selected patients who are at the highest risk. Known risk factors are anemia, cryptogenic stroke and stroke in three brain regions.

  • What are we missing about prognosis?

It is important to keep in mind that all individual patients are different, and that the recurrence stroke risk depend on the underlying cause of the stroke. For example, after cervical artery dissection the recurrence risk is very high in the first two weeks, but the risk of recurrence is very low in the long-term, in contrast for patients with underlying atherosclerosis the risk is always high and will increase further over the years. This information can help to inform patients more accurately in clinical practice.

  • What about the secondary prevention?

Probably the use of antithrombotic therapy should be managed individually depending on both the bleeding and ischemic stroke risk. From the data collected in the Netherlands, the bleeding and ischemic risk are very similar after 5-10 years. Hence, the European guidelines suggest that you can discuss stopping secondary prevention with your patients after 3-5 years if a complete etiological work-up didn’t reveal a cause. Evidence from future clinical trials might be needed to more accurately define if and when we can stop antithrombotic treatment.

This excellent keynote lecture was followed by a lively discussion.

Why is the incidence of stroke in the young rising?

Speaker: Linxin Li (UK)

Dr. Li nicely described the rising incidence of ischemic stroke in the young patients in the last 20 years based on data from the Oxford vascular study. Although the absolute incidence of young stroke showed considerable levels of inconsistencies in other high-income countries, this was consistently less favorable compared to older ages. She nicely demonstrated that the time-trend in the young stroke could not be explained by changes in diagnostic work-up, stroke definition and adjudication, patient behaviour, hospital admission policy or changes in traditional vascular risk factors. Although there is still a high prevalence in modifiable risk factors in young stroke patients which are under-recognized and under-treated. Next, still a lot of research should be done regarding the role of emerging risk factors (migraine, previous auto-immune disease, exercise,…).

Novel types of hereditary small vessel disease: evidence for a unifying mechanism?

Speaker: Elisabeth Tournier-Lasserve

Professor Tournier-Lasserve focused on hereditary causes of small vessel disease. Causative mutations are only identified in 20-25% of the referred patients. Perturbation of the cerebrovascular matrisome is a convergent pathway but through different mechanisms. She nicely demonstrated with the COL4A1 example (HANAC and PADMAL phenotypes), how mutational consequences can be distinct from one class of mutations to another and lead to different small vessel disease (SVD) phenotypes. Many other anomalies can cause an up or down regulation of COL4A1/2 genes and might explain some unresolved SVD cases in the future. Probably a combination of DNA sequencing and functional protein/mRNA fibroblast analysis will be needed to identify them.

Closing comments: PFO as a window on heterogeneity of treatment effect.

Speaker: Guillaume Turc

Professor Turc talked about the selection of people with ischaemic stroke who should undergo PFO closure. The PFO-Associated Stroke Causal Likelihood (PASCAL) classification system is mostly used in clinical practice to select patients for PFO-closure. 15% of young people with ischaemic stroke would be included in the `unlikely` PASCAL category, meaning the stroke was probably not caused by the PFO. Hence these patients are unlikely to derive any benefit from PFO closure (but 95% CI are wide). To determine patients at a high risk for recurrent stroke, a detailed PFO anatomy is important. Data show that patients with both a large shunt and an atrial septal aneurysm are at the highest risk of having a recurrent stroke (SCOPE collaboration) and have the highest treatment effect of PFO closure. Therefore, in the current 2021 AHA/ASA guidelines PFO anatomy has a central role in stratifying patients for PFO closure.

After a lengthy and insightful discussion, the second day of the ESSW was wrapped up.