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

Jonathan G Best,David J Werring,Carmen Barbato,Tarek A Yousry,Hannah Cohen,Henry Houlden,Gargi Banerjee,Duncan Wilson,Martin M Brown,Gareth Ambler,Houwei Du,Clare Shakeshaft,Rustam Al-Shahi Salman,Hans Rolf Jäger,Gregory Y.H Lip,Keith W Muir

doi:10.1212/wnl.0000000000010788

Abstract

ObjectiveTo investigate whether enlarged perivascular spaces (PVS) within the basal ganglia or deep cerebral white matter are risk factors for intracranial hemorrhage in patients taking oral anticoagulants (OACs), independent of established clinical and radiologic risk factors, we conducted a post hoc analysis of Clinical Relevance of Microbleeds in Stroke (CROMIS-2) (atrial fibrillation [AF]), a prospective inception cohort study.MethodsPatients with atrial fibrillation and recent TIA or ischemic stroke underwent standardized MRI prior to starting OAC. We rated basal ganglia PVS (BGPVS) and centrum semiovale PVS (CSOPVS), 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.ResultsA total of 1,386 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 (hazard ratio [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.ConclusionEnlarged 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.

Highlights

Patients with atrial fibrillation and recent TIA or ischemic stroke underwent standardized MRI prior to starting oral anticoagulants (OACs)
In a multivariable model incorporating all variables with significant associations in univariable analysis, >10 basal ganglia PVS (BGPVS) and diabetes (HR 3.91, 95% CI 1.34–11.4) remained significant risk factors for symptomatic intracranial hemorrhage (sICH)
Enlarged BGPVS might be a novel risk factor for OAC-related intracerebral hemorrhage (ICH). The strength of this association and potential use in predicting ICH in clinical practice should be investigated in larger cohorts

Summary

Methods

Patients with atrial fibrillation and recent TIA or ischemic stroke underwent standardized MRI prior to starting OAC. The primary outcome was symptomatic intracranial hemorrhage (sICH). Study design We conducted a post hoc analysis of the Clinical Relevance of Microbleeds in Stroke (CROMIS-2) (AF) study, a multicenter prospective inception cohort study of the relationship between CMBs and anticoagulant-related symptomatic intracranial hemorrhage (sICH). The design, full description of the cohort, and primary results of this study have been published elsewhere.[11] Briefly, we recruited adult patients with AF initiating oral anticoagulation after recent ischemic stroke or TIA from 79 hospitals in the United Kingdom and 1 in the Netherlands between August 2011 and July 2015. The primary outcome was sICH, defined as brain imaging evidence of nontraumatic spontaneous intracranial hemorrhage with appropriate clinical symptoms

Results

Discussion

Conclusion