Introduction: Cerebral venous sinus thrombosis (CVST) occurs in 3-4 per 1 million individuals per year, accounting for approximately 1% of all strokes. Multiple etiologic risk factors for CVST have been identified, with known inherited thrombophilias accounting for 22% of cases. In 15% of cases, no known risk factor is identified. Studying the genetics of CVST holds the potential to identify at-risk groups, determine disease severity and prognosis, and consider novel therapies. BEAST is an international effort to identify genetic determinants of CVST, from which a recent discovery genome-wide association study (GWAS) identified 2 new associated loci.
Methods: We are enrolling patients at least 18 years of age with a diagnosis of CVST who are willing to provide informed consent and a biospecimen to a central DNA repository. Patients are identified prospectively in clinical practice, and retrospectively using the Univ of Virginia clinical data repository.
Results: Since 2012, twenty-eight patients have been enrolled. Demographic and phenotypic data are presented in the Table. Patients range in age from 19 to 65 years, with a mean of 40.5 (SD 14). Headache was the most common presenting symptom, occurring in 60%, followed by seizure (25%), mental status disturbance (21%), aphasia (11%) and mono- or hemiparesis (7%). Imaging revealed focal cerebral edema and/or venous infarction in 7 patients (25%) and hemorrhage in 5 patients (18%); no arteriovenous fistulae were identified. Acute treatments included intravenous or low molecular weight heparin (25/28, 89%) and anti-epileptic medications (7/28, 25%); three patients underwent local thrombolysis or endovascular intervention (11%).
Conclusion: Understanding the association between phenotype and genetic determinants of CVST has the potential to advance the diagnosis and management of this challenging entity. Enrollment in BEAST continues and a replication cohort GWAS is anticipated in the near future.