Microbleeds, Cerebral Hemorrhage, and Functional Outcome after Stroke Thrombolysis: Individual Patient Data Meta-Analysis

Andreas Charidimou, Guillaume Turc, Catherine Oppenheim, Shenqiang Yan, Jan F. Scheitz, Hebun Erdur, Pascal P. Klinger-Gratz, Marwan El-Koussy, Wakoh Takahashi, Yusuke Moriya, Duncan Wilson, Stella Kidwell, Jeffrey L. Saver, Asma Sallem, Solene Moulin, Myriam Edjlali-Goujon, Vincent Thijs, Zoe Fox, Ashkan Shoamanesh, Gregory W. AlbersHeinrich P. Mattle, Oscar R. Benavente, H. Rolf Jäger, Gareth Ambler, Junya Aoki, Jean Claude Baron, Kazumi Kimura, Wataru Kakuda, Shunya Takizawa, Simon Jung, Christian H. Nolte, Min Lou, Charlotte Cordonnier, David J. Werring

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background and Purpose-We assessed whether the presence, number, and distribution of cerebral microbleeds (CMBs) on pre-intravenous thrombolysis MRI scans of acute ischemic stroke patients are associated with an increased risk of intracerebral hemorrhage (ICH) or poor functional outcome. Methods-We performed an individual patient data meta-analysis, including prospective and retrospective studies of acute ischemic stroke treated with intravenous tissue-type plasminogen activator. Using multilevel mixed-effects logistic regression, we investigated associations of pre-treatment CMB presence, burden (1, 2-4, ≥5, and >10), and presumed pathogenesis (cerebral amyloid angiopathy defined as strictly lobar CMBs and noncerebral amyloid angiopathy) with symptomatic ICH, parenchymal hematoma (within [parenchymal hemorrhage, PH] and remote from the ischemic area [remote parenchymal hemorrhage, PHr]), and poor 3-to 6-month functional outcome (modified Rankin score >2). Results-In 1973 patients from 8 centers, the crude prevalence of CMBs was 526 of 1973 (26.7%). A total of 77 of 1973 (3.9%) patients experienced symptomatic ICH, 210 of 1806 (11.6%) experienced PH, and 56 of 1720 (3.3%) experienced PHr. In adjusted analyses, patients with CMBs (compared with those without CMBs) had increased risk of PH (odds ratio: 1.50; 95% confidence interval: 1.09-2.07; P=0.013) and PHr (odds ratio: 3.04; 95% confidence interval: 1.73-5.35; P<0.001) but not symptomatic ICH. Both cerebral amyloid angiopathy and noncerebral amyloid angiopathy patterns of CMBs were associated with PH and PHr. Increasing CMB burden category was associated with the risk of symptomatic ICH (P=0.014), PH (P=0.013), and PHr (P<0.00001). Five or more and >10 CMBs independently predicted poor 3-to 6-month outcome (odds ratio: 1.85; 95% confidence interval: 1.10-3.12; P=0.020; and odds ratio: 3.99; 95% confidence interval: 1.55-10.22; P=0.004, respectively). Conclusions-Increasing CMB burden is associated with increased risk of ICH (including PHr) and poor 3-to 6-month functional outcome after intravenous thrombolysis for acute ischemic stroke.

Original languageEnglish (US)
Pages (from-to)2084-2090
Number of pages7
JournalStroke
Volume48
Issue number8
DOIs
StatePublished - Aug 1 2017

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Cerebral Hemorrhage
Meta-Analysis
Stroke
Hemorrhage
Odds Ratio
Confidence Intervals
Cerebral Amyloid Angiopathy
Tissue Plasminogen Activator
Hematoma
Retrospective Studies
Logistic Models
Magnetic Resonance Imaging
Prospective Studies

Keywords

  • cerebral hemorrhage
  • cerebral small vessel disease
  • magnetic resonance imaging
  • prevalence
  • stroke

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

Cite this

Charidimou, A., Turc, G., Oppenheim, C., Yan, S., Scheitz, J. F., Erdur, H., ... Werring, D. J. (2017). Microbleeds, Cerebral Hemorrhage, and Functional Outcome after Stroke Thrombolysis: Individual Patient Data Meta-Analysis. Stroke, 48(8), 2084-2090. https://doi.org/10.1161/STROKEAHA.116.012992

Microbleeds, Cerebral Hemorrhage, and Functional Outcome after Stroke Thrombolysis : Individual Patient Data Meta-Analysis. / Charidimou, Andreas; Turc, Guillaume; Oppenheim, Catherine; Yan, Shenqiang; Scheitz, Jan F.; Erdur, Hebun; Klinger-Gratz, Pascal P.; El-Koussy, Marwan; Takahashi, Wakoh; Moriya, Yusuke; Wilson, Duncan; Kidwell, Stella; Saver, Jeffrey L.; Sallem, Asma; Moulin, Solene; Edjlali-Goujon, Myriam; Thijs, Vincent; Fox, Zoe; Shoamanesh, Ashkan; Albers, Gregory W.; Mattle, Heinrich P.; Benavente, Oscar R.; Jäger, H. Rolf; Ambler, Gareth; Aoki, Junya; Baron, Jean Claude; Kimura, Kazumi; Kakuda, Wataru; Takizawa, Shunya; Jung, Simon; Nolte, Christian H.; Lou, Min; Cordonnier, Charlotte; Werring, David J.

In: Stroke, Vol. 48, No. 8, 01.08.2017, p. 2084-2090.

Research output: Contribution to journalArticle

Charidimou, A, Turc, G, Oppenheim, C, Yan, S, Scheitz, JF, Erdur, H, Klinger-Gratz, PP, El-Koussy, M, Takahashi, W, Moriya, Y, Wilson, D, Kidwell, S, Saver, JL, Sallem, A, Moulin, S, Edjlali-Goujon, M, Thijs, V, Fox, Z, Shoamanesh, A, Albers, GW, Mattle, HP, Benavente, OR, Jäger, HR, Ambler, G, Aoki, J, Baron, JC, Kimura, K, Kakuda, W, Takizawa, S, Jung, S, Nolte, CH, Lou, M, Cordonnier, C & Werring, DJ 2017, 'Microbleeds, Cerebral Hemorrhage, and Functional Outcome after Stroke Thrombolysis: Individual Patient Data Meta-Analysis', Stroke, vol. 48, no. 8, pp. 2084-2090. https://doi.org/10.1161/STROKEAHA.116.012992
Charidimou, Andreas ; Turc, Guillaume ; Oppenheim, Catherine ; Yan, Shenqiang ; Scheitz, Jan F. ; Erdur, Hebun ; Klinger-Gratz, Pascal P. ; El-Koussy, Marwan ; Takahashi, Wakoh ; Moriya, Yusuke ; Wilson, Duncan ; Kidwell, Stella ; Saver, Jeffrey L. ; Sallem, Asma ; Moulin, Solene ; Edjlali-Goujon, Myriam ; Thijs, Vincent ; Fox, Zoe ; Shoamanesh, Ashkan ; Albers, Gregory W. ; Mattle, Heinrich P. ; Benavente, Oscar R. ; Jäger, H. Rolf ; Ambler, Gareth ; Aoki, Junya ; Baron, Jean Claude ; Kimura, Kazumi ; Kakuda, Wataru ; Takizawa, Shunya ; Jung, Simon ; Nolte, Christian H. ; Lou, Min ; Cordonnier, Charlotte ; Werring, David J. / Microbleeds, Cerebral Hemorrhage, and Functional Outcome after Stroke Thrombolysis : Individual Patient Data Meta-Analysis. In: Stroke. 2017 ; Vol. 48, No. 8. pp. 2084-2090.
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abstract = "Background and Purpose-We assessed whether the presence, number, and distribution of cerebral microbleeds (CMBs) on pre-intravenous thrombolysis MRI scans of acute ischemic stroke patients are associated with an increased risk of intracerebral hemorrhage (ICH) or poor functional outcome. Methods-We performed an individual patient data meta-analysis, including prospective and retrospective studies of acute ischemic stroke treated with intravenous tissue-type plasminogen activator. Using multilevel mixed-effects logistic regression, we investigated associations of pre-treatment CMB presence, burden (1, 2-4, ≥5, and >10), and presumed pathogenesis (cerebral amyloid angiopathy defined as strictly lobar CMBs and noncerebral amyloid angiopathy) with symptomatic ICH, parenchymal hematoma (within [parenchymal hemorrhage, PH] and remote from the ischemic area [remote parenchymal hemorrhage, PHr]), and poor 3-to 6-month functional outcome (modified Rankin score >2). Results-In 1973 patients from 8 centers, the crude prevalence of CMBs was 526 of 1973 (26.7{\%}). A total of 77 of 1973 (3.9{\%}) patients experienced symptomatic ICH, 210 of 1806 (11.6{\%}) experienced PH, and 56 of 1720 (3.3{\%}) experienced PHr. In adjusted analyses, patients with CMBs (compared with those without CMBs) had increased risk of PH (odds ratio: 1.50; 95{\%} confidence interval: 1.09-2.07; P=0.013) and PHr (odds ratio: 3.04; 95{\%} confidence interval: 1.73-5.35; P<0.001) but not symptomatic ICH. Both cerebral amyloid angiopathy and noncerebral amyloid angiopathy patterns of CMBs were associated with PH and PHr. Increasing CMB burden category was associated with the risk of symptomatic ICH (P=0.014), PH (P=0.013), and PHr (P<0.00001). Five or more and >10 CMBs independently predicted poor 3-to 6-month outcome (odds ratio: 1.85; 95{\%} confidence interval: 1.10-3.12; P=0.020; and odds ratio: 3.99; 95{\%} confidence interval: 1.55-10.22; P=0.004, respectively). Conclusions-Increasing CMB burden is associated with increased risk of ICH (including PHr) and poor 3-to 6-month functional outcome after intravenous thrombolysis for acute ischemic stroke.",
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TY - JOUR

T1 - Microbleeds, Cerebral Hemorrhage, and Functional Outcome after Stroke Thrombolysis

T2 - Individual Patient Data Meta-Analysis

AU - Charidimou, Andreas

AU - Turc, Guillaume

AU - Oppenheim, Catherine

AU - Yan, Shenqiang

AU - Scheitz, Jan F.

AU - Erdur, Hebun

AU - Klinger-Gratz, Pascal P.

AU - El-Koussy, Marwan

AU - Takahashi, Wakoh

AU - Moriya, Yusuke

AU - Wilson, Duncan

AU - Kidwell, Stella

AU - Saver, Jeffrey L.

AU - Sallem, Asma

AU - Moulin, Solene

AU - Edjlali-Goujon, Myriam

AU - Thijs, Vincent

AU - Fox, Zoe

AU - Shoamanesh, Ashkan

AU - Albers, Gregory W.

AU - Mattle, Heinrich P.

AU - Benavente, Oscar R.

AU - Jäger, H. Rolf

AU - Ambler, Gareth

AU - Aoki, Junya

AU - Baron, Jean Claude

AU - Kimura, Kazumi

AU - Kakuda, Wataru

AU - Takizawa, Shunya

AU - Jung, Simon

AU - Nolte, Christian H.

AU - Lou, Min

AU - Cordonnier, Charlotte

AU - Werring, David J.

PY - 2017/8/1

Y1 - 2017/8/1

N2 - Background and Purpose-We assessed whether the presence, number, and distribution of cerebral microbleeds (CMBs) on pre-intravenous thrombolysis MRI scans of acute ischemic stroke patients are associated with an increased risk of intracerebral hemorrhage (ICH) or poor functional outcome. Methods-We performed an individual patient data meta-analysis, including prospective and retrospective studies of acute ischemic stroke treated with intravenous tissue-type plasminogen activator. Using multilevel mixed-effects logistic regression, we investigated associations of pre-treatment CMB presence, burden (1, 2-4, ≥5, and >10), and presumed pathogenesis (cerebral amyloid angiopathy defined as strictly lobar CMBs and noncerebral amyloid angiopathy) with symptomatic ICH, parenchymal hematoma (within [parenchymal hemorrhage, PH] and remote from the ischemic area [remote parenchymal hemorrhage, PHr]), and poor 3-to 6-month functional outcome (modified Rankin score >2). Results-In 1973 patients from 8 centers, the crude prevalence of CMBs was 526 of 1973 (26.7%). A total of 77 of 1973 (3.9%) patients experienced symptomatic ICH, 210 of 1806 (11.6%) experienced PH, and 56 of 1720 (3.3%) experienced PHr. In adjusted analyses, patients with CMBs (compared with those without CMBs) had increased risk of PH (odds ratio: 1.50; 95% confidence interval: 1.09-2.07; P=0.013) and PHr (odds ratio: 3.04; 95% confidence interval: 1.73-5.35; P<0.001) but not symptomatic ICH. Both cerebral amyloid angiopathy and noncerebral amyloid angiopathy patterns of CMBs were associated with PH and PHr. Increasing CMB burden category was associated with the risk of symptomatic ICH (P=0.014), PH (P=0.013), and PHr (P<0.00001). Five or more and >10 CMBs independently predicted poor 3-to 6-month outcome (odds ratio: 1.85; 95% confidence interval: 1.10-3.12; P=0.020; and odds ratio: 3.99; 95% confidence interval: 1.55-10.22; P=0.004, respectively). Conclusions-Increasing CMB burden is associated with increased risk of ICH (including PHr) and poor 3-to 6-month functional outcome after intravenous thrombolysis for acute ischemic stroke.

AB - Background and Purpose-We assessed whether the presence, number, and distribution of cerebral microbleeds (CMBs) on pre-intravenous thrombolysis MRI scans of acute ischemic stroke patients are associated with an increased risk of intracerebral hemorrhage (ICH) or poor functional outcome. Methods-We performed an individual patient data meta-analysis, including prospective and retrospective studies of acute ischemic stroke treated with intravenous tissue-type plasminogen activator. Using multilevel mixed-effects logistic regression, we investigated associations of pre-treatment CMB presence, burden (1, 2-4, ≥5, and >10), and presumed pathogenesis (cerebral amyloid angiopathy defined as strictly lobar CMBs and noncerebral amyloid angiopathy) with symptomatic ICH, parenchymal hematoma (within [parenchymal hemorrhage, PH] and remote from the ischemic area [remote parenchymal hemorrhage, PHr]), and poor 3-to 6-month functional outcome (modified Rankin score >2). Results-In 1973 patients from 8 centers, the crude prevalence of CMBs was 526 of 1973 (26.7%). A total of 77 of 1973 (3.9%) patients experienced symptomatic ICH, 210 of 1806 (11.6%) experienced PH, and 56 of 1720 (3.3%) experienced PHr. In adjusted analyses, patients with CMBs (compared with those without CMBs) had increased risk of PH (odds ratio: 1.50; 95% confidence interval: 1.09-2.07; P=0.013) and PHr (odds ratio: 3.04; 95% confidence interval: 1.73-5.35; P<0.001) but not symptomatic ICH. Both cerebral amyloid angiopathy and noncerebral amyloid angiopathy patterns of CMBs were associated with PH and PHr. Increasing CMB burden category was associated with the risk of symptomatic ICH (P=0.014), PH (P=0.013), and PHr (P<0.00001). Five or more and >10 CMBs independently predicted poor 3-to 6-month outcome (odds ratio: 1.85; 95% confidence interval: 1.10-3.12; P=0.020; and odds ratio: 3.99; 95% confidence interval: 1.55-10.22; P=0.004, respectively). Conclusions-Increasing CMB burden is associated with increased risk of ICH (including PHr) and poor 3-to 6-month functional outcome after intravenous thrombolysis for acute ischemic stroke.

KW - cerebral hemorrhage

KW - cerebral small vessel disease

KW - magnetic resonance imaging

KW - prevalence

KW - stroke

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