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 A Yousry; Rustam Al-Shahi Salman; Gregory Y H Lip; Henry Houlden; Martin M Brown; Keith W Muir; Hans Rolf Jäger; David J Werring; Clinical relevance of Microbleeds in Stroke (CROMIS-2) collaborators

doi:10.1212/WNL.0000000000010788

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 A Yousry, Rustam Al-Shahi Salman, Gregory Y H Lip, Henry Houlden, Martin M Brown, Keith W Muir, Hans Rolf Jäger, David J Werring, Clinical relevance of Microbleeds in Stroke (CROMIS-2) collaborators

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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.

Original language	English
Journal	Neurology
Volume	95
Issue number	16
Pages (from-to)	e2192-e2199
ISSN	0028-3878
DOIs	https://doi.org/10.1212/WNL.0000000000010788
Publication status	Published - 20 Oct 2020

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Best et al. (2020) Association of enlarged perivascular spaces and anticoagulant-related intracranial hemorrhageFinal published version, 360 KBLicence: CC BY 4.0

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Best, J. G., Barbato, C., Ambler, G., Du, H., Banerjee, G., Wilson, D., Shakeshaft, C., Cohen, H., Yousry, T. A., Salman, R. A-S., Lip, G. Y. H., Houlden, H., Brown, M. M., Muir, K. W., Jäger, H. R., Werring, D. J., & Clinical relevance of Microbleeds in Stroke (CROMIS-2) collaborators (2020). Association of enlarged perivascular spaces and anticoagulant-related intracranial hemorrhage. Neurology, 95(16), e2192-e2199. Advance online publication. https://doi.org/10.1212/WNL.0000000000010788

@article{3c9aa1378bda4024be82e8fc36a8290f,

title = "Association of enlarged perivascular spaces and anticoagulant-related intracranial hemorrhage",

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.",

author = "Best, {Jonathan G} and Carmen Barbato and Gareth Ambler and Houwei Du and Gargi Banerjee and Duncan Wilson and Clare Shakeshaft and Hannah Cohen and Yousry, {Tarek A} and Salman, {Rustam Al-Shahi} and Lip, {Gregory Y H} and Henry Houlden and Brown, {Martin M} and Muir, {Keith W} and J{\"a}ger, {Hans Rolf} and Werring, {David J} and {Clinical relevance of Microbleeds in Stroke (CROMIS-2) collaborators}",

year = "2020",

month = oct,

day = "20",

doi = "10.1212/WNL.0000000000010788",

language = "English",

volume = "95",

pages = "e2192--e2199",

journal = "Neurology",

issn = "0028-3878",

publisher = "Lippincott Williams & Wilkins",

number = "16",

}

Best, JG, Barbato, C, Ambler, G, Du, H, Banerjee, G, Wilson, D, Shakeshaft, C, Cohen, H, Yousry, TA, Salman, RA-S, Lip, GYH, Houlden, H, Brown, MM, Muir, KW, Jäger, HR, Werring, DJ & Clinical relevance of Microbleeds in Stroke (CROMIS-2) collaborators 2020, 'Association of enlarged perivascular spaces and anticoagulant-related intracranial hemorrhage', Neurology, vol. 95, no. 16, pp. e2192-e2199. https://doi.org/10.1212/WNL.0000000000010788

TY - JOUR

T1 - Association of enlarged perivascular spaces and anticoagulant-related intracranial hemorrhage

AU - Best, Jonathan G

AU - Barbato, Carmen

AU - Ambler, Gareth

AU - Du, Houwei

AU - Banerjee, Gargi

AU - Wilson, Duncan

AU - Shakeshaft, Clare

AU - Cohen, Hannah

AU - Yousry, Tarek A

AU - Salman, Rustam Al-Shahi

AU - Lip, Gregory Y H

AU - Houlden, Henry

AU - Brown, Martin M

AU - Muir, Keith W

AU - Jäger, Hans Rolf

AU - Werring, David J

AU - Clinical relevance of Microbleeds in Stroke (CROMIS-2) collaborators

PY - 2020/10/20

Y1 - 2020/10/20

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85093894470&partnerID=8YFLogxK

U2 - 10.1212/WNL.0000000000010788

DO - 10.1212/WNL.0000000000010788

M3 - Journal article

C2 - 32934168

SN - 0028-3878

VL - 95

SP - e2192-e2199

JO - Neurology

JF - Neurology

IS - 16

ER -

Association of enlarged perivascular spaces and anticoagulant-related intracranial hemorrhage

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