Association of enlarged perivascular spaces and anticoagulant-related intracranial hemorrhage
Jonathan G. Best, Carmen Barbato, Gareth Ambler, Houwei Du, Gargi Banerjee, Duncan Wilson, Clare Shakeshaft, Hannah Cohen, Tarek Yousry, Rustam Al‐Shahi Salman, Gregory Y.H. Lip, Henry Houlden, Martin M. Brown, Keith W. Muir, Hans Rolf Jäger, David J. Werring, P. Adrian, Chris Patterson, Christopher Price, Abduelbaset Elmarimi, Anthea Parry, Arumug Nallasivam, Azlisham Mohd Nor, Bernard Esis, Fábio A. Nascimento, David Bruce, Biju Bhaskaran, Christine Roffe, Claire Cullen, Clare Holmes, David Cohen, Claire Cullen, Claire Cullen, Claire Cullen, Claire Cullen, Claire Cullen, Claire Cullen, Claire Cullen, Claire Cullen, Claire Cullen, Claire Cullen, Claire Cullen, Claire Cullen, David Hargroves, David Mangion, Dinesh Chadha, Djamil Vahidassr, Dulka Manawadu, Elio Giallombardo, Elizabeth A. Warburton, Enrico Flossman, Gunaratam Gunathilagan, Harald Proschel, Hedley Emsley, Ijaz Anwar, Ilse Burger, James Okwera, Janet Putterill, Janice O’Connell, John Bamford, John Corrigan, Jon Scott, Jonathan Birns, Karen Kee, Kari Saastamoinen, Kath Pasco, Krishna Dani, Lakshmanan Sekaran, Lillian Choy, Liz Iveson, Maam Mamun, Mahmud Sajid, Martin Cooper, Matthew B. Burn, Matthew Smith, Mick Power, Michelle Davis, Nigel Smyth, Roland Veltkamp, Pankaj Sharma, Paul Guyler, Paul O’Mahony, Peter Wilkinson, Prabel Datta, Prasanna Aghoram, Rachel Marsh, Robert Luder, Sanjeevikumar Meenakishundaram, Santhosh Subramonian, Simon Leach, Sissi Ispoglou, Sreeman Andole, Timothy J. England, Aravindakshan Manoj, Frances Harrington, Habiba Rehman, Jane Sword, Julie Staals, Karim Mahawish, Kirsty Harkness
Abstract
<h3>Objective</h3> To 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. <h3>Methods</h3> Patients 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. <h3>Results</h3> A 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, <i>p</i> = 0.001) and diabetes (HR 3.91, 95% CI 1.34–11.4) remained significant risk factors for sICH. <h3>Conclusion</h3> 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.