. 2020 Oct 20;95(16):e2192-e2199.

doi: 10.1212/WNL.0000000000010788. Epub 2020 Sep 15.

Association of enlarged perivascular spaces and anticoagulant-related intracranial hemorrhage

Jonathan G Best¹, Carmen Barbato¹, Gareth Ambler¹, Houwei Du¹, Gargi Banerjee¹, Duncan Wilson¹, Clare Shakeshaft¹, Hannah Cohen¹, Tarek A Yousry¹, Rustam Al-Shahi Salman¹, Gregory Y H Lip¹, Henry Houlden¹, Martin M Brown¹, Keith W Muir¹, Hans Rolf Jäger¹, David J Werring²; Clinical Relevance of Microbleeds in Stroke (CROMIS-2) collaborators

Collaborators, Affiliations

Collaborators

Clinical Relevance of Microbleeds in Stroke (CROMIS-2) collaborators:
Parry-Jones Adrian, Chris Patterson, Christopher Price, Abduelbaset Elmarimi, Anthea Parry, Arumug Nallasivam, Azlisham Mohd Nor, Bernard Esis, Fabio 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 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 Burn, Matthew Smith, Michael Power, Michelle Davis, Nigel Smyth, Roland Veltkamp Prof, 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 England, Aravindakshan Manoj, Frances Harrington, Habiba Rehman, Jane Sword, Julie Staals Prof, Karim Mahawish, Kirsty Harkness, Louise Shaw, Michael McCormich, Nikola Sprigg Prof, Syed Mansoor, Vinodh Krishnamurthy

Affiliations

¹ From the Stroke Research Center (J.G.B., C.B., H.D., G.B., D.W., C.S., M.M.B., D.J.W.) and Lysholm Department of Neuroradiology and the Neuroradiological Academic Unit (T.A.Y., H.R.J.), Department of Brain Repair and Rehabilitation, UCL Queen Square Institute of Neurology; Department of Statistical Science (G.A.), Haemostasis Research Unit, Department of Haematology (H.C.), University College London, UK; Stroke Research Center, Department of Neurology (H.D.), Fujian Medical University Union Hospital, Fuzhou, China; Center for Clinical Brain Sciences, School of Clinical Sciences (R.A.-S.S.), University of Edinburgh; Liverpool Center for Cardiovascular Science (G.Y.H.L.), University of Liverpool and Liverpool Heart and Chest Hospital, UK; Aalborg Thrombosis Research Unit, Department of Clinical Medicine (G.Y.H.L.), Aalborg University, Denmark; Department of Molecular Neuroscience (H.H.), UCL Queen Square Institute of Neurology and the National Hospital for Neurology and Neurosurgery, London; and Institute of Neuroscience & Psychology (K.W.M.), University of Glasgow, Queen Elizabeth University Hospital, UK.
² From the Stroke Research Center (J.G.B., C.B., H.D., G.B., D.W., C.S., M.M.B., D.J.W.) and Lysholm Department of Neuroradiology and the Neuroradiological Academic Unit (T.A.Y., H.R.J.), Department of Brain Repair and Rehabilitation, UCL Queen Square Institute of Neurology; Department of Statistical Science (G.A.), Haemostasis Research Unit, Department of Haematology (H.C.), University College London, UK; Stroke Research Center, Department of Neurology (H.D.), Fujian Medical University Union Hospital, Fuzhou, China; Center for Clinical Brain Sciences, School of Clinical Sciences (R.A.-S.S.), University of Edinburgh; Liverpool Center for Cardiovascular Science (G.Y.H.L.), University of Liverpool and Liverpool Heart and Chest Hospital, UK; Aalborg Thrombosis Research Unit, Department of Clinical Medicine (G.Y.H.L.), Aalborg University, Denmark; Department of Molecular Neuroscience (H.H.), UCL Queen Square Institute of Neurology and the National Hospital for Neurology and Neurosurgery, London; and Institute of Neuroscience & Psychology (K.W.M.), University of Glasgow, Queen Elizabeth University Hospital, UK. d.werring@ucl.ac.uk.

PMID: 32934168
PMCID: PMC7713790
DOI: 10.1212/WNL.0000000000010788

Association of enlarged perivascular spaces and anticoagulant-related intracranial hemorrhage

Jonathan G Best et al. Neurology. 2020.

. 2020 Oct 20;95(16):e2192-e2199.

doi: 10.1212/WNL.0000000000010788. Epub 2020 Sep 15.

Authors

Collaborators

Clinical Relevance of Microbleeds in Stroke (CROMIS-2) collaborators:
Parry-Jones Adrian, Chris Patterson, Christopher Price, Abduelbaset Elmarimi, Anthea Parry, Arumug Nallasivam, Azlisham Mohd Nor, Bernard Esis, Fabio 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 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 Burn, Matthew Smith, Michael Power, Michelle Davis, Nigel Smyth, Roland Veltkamp Prof, 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 England, Aravindakshan Manoj, Frances Harrington, Habiba Rehman, Jane Sword, Julie Staals Prof, Karim Mahawish, Kirsty Harkness, Louise Shaw, Michael McCormich, Nikola Sprigg Prof, Syed Mansoor, Vinodh Krishnamurthy

Affiliations

¹ From the Stroke Research Center (J.G.B., C.B., H.D., G.B., D.W., C.S., M.M.B., D.J.W.) and Lysholm Department of Neuroradiology and the Neuroradiological Academic Unit (T.A.Y., H.R.J.), Department of Brain Repair and Rehabilitation, UCL Queen Square Institute of Neurology; Department of Statistical Science (G.A.), Haemostasis Research Unit, Department of Haematology (H.C.), University College London, UK; Stroke Research Center, Department of Neurology (H.D.), Fujian Medical University Union Hospital, Fuzhou, China; Center for Clinical Brain Sciences, School of Clinical Sciences (R.A.-S.S.), University of Edinburgh; Liverpool Center for Cardiovascular Science (G.Y.H.L.), University of Liverpool and Liverpool Heart and Chest Hospital, UK; Aalborg Thrombosis Research Unit, Department of Clinical Medicine (G.Y.H.L.), Aalborg University, Denmark; Department of Molecular Neuroscience (H.H.), UCL Queen Square Institute of Neurology and the National Hospital for Neurology and Neurosurgery, London; and Institute of Neuroscience & Psychology (K.W.M.), University of Glasgow, Queen Elizabeth University Hospital, UK.
² From the Stroke Research Center (J.G.B., C.B., H.D., G.B., D.W., C.S., M.M.B., D.J.W.) and Lysholm Department of Neuroradiology and the Neuroradiological Academic Unit (T.A.Y., H.R.J.), Department of Brain Repair and Rehabilitation, UCL Queen Square Institute of Neurology; Department of Statistical Science (G.A.), Haemostasis Research Unit, Department of Haematology (H.C.), University College London, UK; Stroke Research Center, Department of Neurology (H.D.), Fujian Medical University Union Hospital, Fuzhou, China; Center for Clinical Brain Sciences, School of Clinical Sciences (R.A.-S.S.), University of Edinburgh; Liverpool Center for Cardiovascular Science (G.Y.H.L.), University of Liverpool and Liverpool Heart and Chest Hospital, UK; Aalborg Thrombosis Research Unit, Department of Clinical Medicine (G.Y.H.L.), Aalborg University, Denmark; Department of Molecular Neuroscience (H.H.), UCL Queen Square Institute of Neurology and the National Hospital for Neurology and Neurosurgery, London; and Institute of Neuroscience & Psychology (K.W.M.), University of Glasgow, Queen Elizabeth University Hospital, UK. d.werring@ucl.ac.uk.

PMID: 32934168
PMCID: PMC7713790
DOI: 10.1212/WNL.0000000000010788

Abstract

Objective: 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.

Methods: 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.

Results: 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, 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.

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Figures

**Figure 1. Study flowchart**
CROMIS-2 (AF) = Clinical Relevance of Microbleeds in Stroke (atrial fibrillation); FLAIR = fluid-attenuated inversion recovery; HTN = hypertension.

**Figure 2. Cumulative probability of symptomatic intracranial hemorrhage by basal ganglia (BG) perivascular space (PVS) rating**

See this image and copyright information in PMC

Comment in

MRI-visible enlarged perivascular spaces: Beyond microbleeds to predict intracerebral hemorrhage.
Raposo N, Viswanathan A. Raposo N, et al. Neurology. 2020 Oct 20;95(16):709-710. doi: 10.1212/WNL.0000000000010790. Epub 2020 Sep 15. Neurology. 2020. PMID: 32934173 No abstract available.

References

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Association of enlarged perivascular spaces and anticoagulant-related intracranial hemorrhage

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Association of enlarged perivascular spaces and anticoagulant-related intracranial hemorrhage

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