FROM QUESTION TO CURE: CEREBRAL VENOUS THROMBOSIS AND THE BEAST STUDY

Abstract Background Cerebral venous thrombosis is a rare cause of stroke that primarily affects young women of reproductive age, with a death or dependency rate ranging from 6%–15%. We evaluated the adult cerebral venous thrombosis population of European ancestry to determine how factors such as age, gender, and risk factors, including genetic mutation influence the onset, severity, and long-term outcomes of cerebral venous thrombosis. Methods The BEAST study (Biorepository to Establish the Aetiology of Sinovenous Thrombosis) is a prospective observational study that recruited 1309 cerebral venous thrombosis patients (aged ≥18 years) of European ancestry from 11 countries in the UK, Europe, the USA, and Mexico from 2000 to 2018. Additionally, a meta-analysis evaluated 25 studies involving 2301 patients and compares the safety and effectiveness of direct oral anticoagulants (DOACs) and warfarin for the long-term (≥6 months) treatment of cerebral venous thrombosis. Results Women suffered cerebral venous thrombosis 9 years earlier than men, and women with ≥1 risk factor suffer cerebral venous thrombosis ~12 years earlier than those with no identifiable risk factors. Further, the likelihood of cerebral venous thrombosis is ~4 times higher at ≥45 years in those with malignancy (Odds Ratio [OR]: 3.6, 95% CI 1.4–9.0; P = 0.006). Furthermore, using genome wide analyses we identify PROC (protein C) SNPs (rs1799810, rs41280570, rs1158867, rs2069919, and rs5937) as potential genetic determinants linked to an increased risk (OR ~ 1.3) of cerebral venous thrombosis in Europeans. Although cerebral venous thrombosis is a female-dominant disease, we observed that men are ~2-fold more likely to suffer from coma compared to women. Additionally, a meta-analysis found comparable long-term outcomes represented by good clinical outcomes between the DOACs and warfarin arms. However, a subgroup analysis found that the recurrence of venous thrombosis was lower in the rivaroxaban group than in warfarin (2.2% vs. 8.5%, RR = 0.33, 95% CI = 0.11–0.98; P = 0.05). Conclusion Early diagnosis and effective management strategies are essential for enhancing the prognosis in adult cerebral venous thrombosis, a disease that has previously been poorly studied.