Association of enlarged perivascular spaces and anticoagulant-related intracranial hemorrhage.

Objective To investigate whether enlarged perivascular spaces within the basal ganglia or deep cerebral white matter are risk factors for intracranial hemorrhage in patients taking oral anticoagulants (OAC), independent of established clinical and radiological risk factors, we conducted a post hoc analysis of CROMIS-2 (AF), a prospective inception cohort study. Methods Patients with atrial fibrillation and recent TIA or ischaemic stroke underwent standardised MR imaging prior to starting OAC. We rated basal ganglia (BGPVS) and centrum semiovale (CSOPVS) perivascular spaces, cerebral microbleeds (CMBs), white matter hyperintensities and lacunes. We dichotomized the PVS rating using a threshold of >10 PVS in the relevant region of either cerebral hemisphere. The primary outcome was symptomatic intracranial hemorrhage (sICH). We identified risk factors for sICH using Cox regression. Results 1386 participants with available clinical and imaging variables were followed up for a mean of 2.34 years. 14 sICH occurred (11 intracerebral). In univariable analysis, diabetes, CMB presence, lacune presence and >10 BGPVS, but not CSOPVS, were associated with sICH. In a multivariable model incorporating all variables with significant associations in univariable analysis, >10 BGPVS (HR 8.96, 95% CI 2.41 – 33.4, p = 0.001) and diabetes (HR 3.91, 95% CI 1.34 – 11.4) remained significant risk factors for sICH. Conclusion Enlarged BGPVS might be a novel risk factor for OAC-related ICH. The strength of this association and potential use in predicting ICH in clinical practice should be investigated in larger cohorts.