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Numerous biological mechanisms contribute to outcome after stroke, including brain injury, inflammation, and repair mechanisms. Clinical genetic studies have the potential to discover biological mechanisms affecting stroke recovery in humans and identify intervention targets. Large sample sizes are needed to detect commonly occurring genetic variations related to stroke brain injury and recovery. However, this usually requires combining data from multiple studies where consistent terminology, methodology, and data collection timelines are essential. Our group of expert stroke and rehabilitation clinicians and researchers with knowledge in genetics of stroke recovery here present recommendations for harmonizing phenotype data with focus on measures suitable for multicenter genetic studies of ischemic stroke brain injury and recovery. Our recommendations have been endorsed by the International Stroke Genetics Consortium.

Background and aims: Increased risk of stroke, particularly large artery stroke (LAS), has been observed in patients with COVID-19. The biological processes underlying the observed higher risk are still unknown. We explored the association between stroke subtypes and COVID-19 susceptibility to understand whether biological mechanisms specific to SARS-CoV-2 uptake/infection could be leading to excess stroke risk in this population. Patients and methods: We constructed a polygenic risk score (PRS) of COVID-19 susceptibility and tested its association with stroke subtypes using individual- and summary-level genetic data (SiGN, MEGASTROKE). We generated co-expression networks of genes involved in SARS-CoV-2 uptake/infection (ACE2, TMPRSS2, BEST3, ISLR2 and ADAM17) based on existing tissue expression libraries. Gene-based association testing was performed using S-PrediXcan and VEGAS2. Permutation independence tests were performed to assess SARS-CoV-2-related gene enrichment in stroke and its subtypes. Results: Our PRS demonstrated an association between COVID-19 susceptibility and LAS in SiGN (OR = 1.05 per SD increase, 95% CI: (1.00, 1.10), p = 0.04) and MEGASTROKE (β = 0.510, 95% CI: (0.242, 0.779), FDR-p = 0.0019). The SARS-CoV-2 risk-related ISLR2 co-expression gene network was significantly associated with genetic risk of LAS in aorta, tibial arteries, and multiple brain regions (P < 0.05). Conclusion: Presence of genetic correlation and significant pathway enrichment suggest that increases in LAS risk reported in COVID-19 patients may be intrinsic to the viral infection, rather than a more generalized response to severe illness. [ABSTRACT FROM AUTHOR]

Rationale Long-term risk of vascular disease is substantially increased after stroke with several models proposed to predict subsequent stroke and other vascular events after an index event. However, recent validation studies demonstrate limited predictive properties of available prognostic models. Aims We aim to determine prediction models of different complexity for the combined vascular end-point of stroke, myocardial infarction, and vascular death at three-years after first-ever stroke. An independent external validation of the developed models will be performed. Design Prospective observational hospital-based cohort study of patients after first-ever stroke. Methods The new predictive models will be developed using the following steps: (1) Development of a basic score based on clinical history data (e.g. hypertension, myocardial infarction, and atrial fibrillation); (2) Development of an advanced score including additional factors such as blood-based biomarkers and results of vascular imaging; (3) Comparing the models fit using different methods (discrimination, calibration); (4) Assessment of clinical utility of an advanced score using methods based on reclassification tables (e.g. net reclassification improvement, integrated discrimination improvement, decision curve analysis); and (5) Investigation of external validity. Outcomes Primary outcome is a combined vascular end-point composed of stroke, myocardial infarction, and vascular death at three-years after stroke. Furthermore, each component of the composite end-point will be investigated individually and the patterns and time points of risk transitions between vascular end-points and stroke sub-types will be determined. [ABSTRACT FROM AUTHOR]

Background and aims Acute occlusions of the large intracranial arteries are relatively resistant to intravenous thrombolysis. Therefore, multimodal approaches combining intravenous thrombolysis with endovascular mechanical recanalization are increasingly being applied. In this setting, intravenous thrombolysis may facilitate subsequent mechanical thrombectomy. To test this hypothesis, we analyzed the influence of intravenous thrombolysis on net intervention time in subsequent endovascular mechanical recanalization. Methods In this retrospective single-center analysis, we compared net intervention time with and without preceding intravenous thrombolysis in patients treated by endovascular mechanical recanalization between 01/2003 and 06/2010. The net intervention time was defined as the interval between the onset of endovascular thrombus manipulation and successful vessel recanalization. Results We identified 65 eligible patients, 35 of whom were treated by intravenous thrombolysis before mechanical therapy. Recanalization was achieved in 26 patients with (74%) and 23 patients without preceding intravenous thrombolysis (77%). In the case of successful recanalization, the net intervention time was significantly shorter in patients with preceding intravenous thrombolysis (24·8 ± 22·8 vs. 44·2 ± 40·5 min; P<0·05). This difference remained significant after restricting the analysis to the patients treated by the Penumbra Stroke System© ( n=32). After three-months, patients with preceding intravenous thrombolysis were more likely to be functionally independent (modified Rankin Scale≤2) than those without ( P<0·05). Conclusions Our findings suggest that preceding intravenous thrombolysis may reduce the intervention time in patients treated by endovascular mechanical recanalization. However, due to the retrospective design of our study, these findings have to be interpreted with caution and need confirmation in a larger patient population. [ABSTRACT FROM AUTHOR]