Risk of symptomatic intracerebral hemorrhage after intravenous thrombolysis in patients with acute ischemic stroke and high cerebral microbleed burden ameta-analysis

Georgios Tsivgoulis, Ramin Zand, Aristeidis H. Katsanos, Guillaume Turc, Christian H. Nolte, Simon Jung, Charlotte Cordonnier, Jochen B. Fiebach, Jan F. Scheitz, Pascal P. Klinger-Gratz, Catherine Oppenheim, Nitin Goyal, Apostolos Safouris, Heinrich P. Mattle, Anne Alexandrov, Peter D. Schellinger, Andrei Alexandrov

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

IMPORTANCE Cerebral microbleeds (CMBs) have been established as an independent predictor of cerebral bleeding. There are contradictory data regarding the potential association of CMB burden with the risk of symptomatic intracerebral hemorrhage (sICH) in patients with acute ischemic stroke (AIS) treated with intravenous thrombolysis (IVT). OBJECTIVE To investigate the association of high CMB burden (>10 CMBs on a pre-IVT magnetic image resonance [MRI] scan) with the risk of sICH following IVT for AIS. DATA SOURCES Eligible studies were identified by searching Medline and Scopus databases. No language or other restrictions were imposed. The literature search was conducted on October 7, 2015. This meta-analysis has adopted the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was written according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) proposal. STUDY SELECTION Eligible prospective study protocols that reported sICH rates in patients with AIS who underwent MRI for CMB screening prior to IVT. DATA EXTRACTION AND SYNTHESIS The reported rates of sICH complicating IVT in patients with AIS with pretreatment MRIwere extracted independently for groups of patients with 0 CMBs (CMB absence), 1 or more CMBs (CMB presence), 1 to 10 CMBs (lowto moderate CMB burden), and more than 10 CMBs (high CMB burden). An individual-patient data meta-analysiswas also performed in the included studies that provided complete patient data sets. MAIN OUTCOMES AND MEASURES Symptomatic intracerebral hemorrhage based on the European Cooperative Acute Stroke Study-II definition (any intracranial bleed with≥4 points worsening on the National Institutes of Health Stroke Scale score). RESULTS We included 9 studies comprising 2479 patients with AIS. The risk of sICH after IVT was found to be higher in patients with evidence of CMB presence, compared with patients without CMBs (risk ratio [RR], 2.36; 95%CI, 1.21-4.61; P = .01). A higher risk for sICH after IVT was detected in patients with high CMB burden (>10 CMBs) when compared with patients with 0 to 10 CMBs (RR, 12.10; 95%CI, 4.36-33.57; P < .001) or 1 to 10 CMBs (RR, 7.01; 95%CI, 3.20-15.38; P < .001) on pretreatment MRI. In the individual-patient data meta-analysis, high CMB burden was associated with increased likelihood of sICH before (unadjusted odds ratio, 31.06; 95%CI, 7.12-135.44; P < .001) and after (adjusted odds ratio, 18.17; 95%CI, 2.39-138.22; P = .005) adjusting for potential confounders. CONCLUSIONS AND RELEVANCE Presence ofCMBand highCMBburdens on pretreatment MRI were independently associated with sICH in patients with AIS treated with IVT. High CMB burden may be included in individual risk stratification scores predicting sICH risk following IVT for AIS.

Original languageEnglish (US)
Pages (from-to)675-683
Number of pages9
JournalJAMA Neurology
Volume73
Issue number6
DOIs
StatePublished - Jun 1 2016

Fingerprint

Cerebral Hemorrhage
Stroke
Odds Ratio
Meta-Analysis
National Institutes of Health (U.S.)
Observational Studies
Epidemiology
Magnetic Resonance Spectroscopy
Language
Magnetic Resonance Imaging

All Science Journal Classification (ASJC) codes

  • Clinical Neurology

Cite this

Risk of symptomatic intracerebral hemorrhage after intravenous thrombolysis in patients with acute ischemic stroke and high cerebral microbleed burden ameta-analysis. / Tsivgoulis, Georgios; Zand, Ramin; Katsanos, Aristeidis H.; Turc, Guillaume; Nolte, Christian H.; Jung, Simon; Cordonnier, Charlotte; Fiebach, Jochen B.; Scheitz, Jan F.; Klinger-Gratz, Pascal P.; Oppenheim, Catherine; Goyal, Nitin; Safouris, Apostolos; Mattle, Heinrich P.; Alexandrov, Anne; Schellinger, Peter D.; Alexandrov, Andrei.

In: JAMA Neurology, Vol. 73, No. 6, 01.06.2016, p. 675-683.

Research output: Contribution to journalArticle

Tsivgoulis, G, Zand, R, Katsanos, AH, Turc, G, Nolte, CH, Jung, S, Cordonnier, C, Fiebach, JB, Scheitz, JF, Klinger-Gratz, PP, Oppenheim, C, Goyal, N, Safouris, A, Mattle, HP, Alexandrov, A, Schellinger, PD & Alexandrov, A 2016, 'Risk of symptomatic intracerebral hemorrhage after intravenous thrombolysis in patients with acute ischemic stroke and high cerebral microbleed burden ameta-analysis', JAMA Neurology, vol. 73, no. 6, pp. 675-683. https://doi.org/10.1001/jamaneurol.2016.0292
Tsivgoulis, Georgios ; Zand, Ramin ; Katsanos, Aristeidis H. ; Turc, Guillaume ; Nolte, Christian H. ; Jung, Simon ; Cordonnier, Charlotte ; Fiebach, Jochen B. ; Scheitz, Jan F. ; Klinger-Gratz, Pascal P. ; Oppenheim, Catherine ; Goyal, Nitin ; Safouris, Apostolos ; Mattle, Heinrich P. ; Alexandrov, Anne ; Schellinger, Peter D. ; Alexandrov, Andrei. / Risk of symptomatic intracerebral hemorrhage after intravenous thrombolysis in patients with acute ischemic stroke and high cerebral microbleed burden ameta-analysis. In: JAMA Neurology. 2016 ; Vol. 73, No. 6. pp. 675-683.
@article{80d758d6f733446986b450fc3cec7ebc,
title = "Risk of symptomatic intracerebral hemorrhage after intravenous thrombolysis in patients with acute ischemic stroke and high cerebral microbleed burden ameta-analysis",
abstract = "IMPORTANCE Cerebral microbleeds (CMBs) have been established as an independent predictor of cerebral bleeding. There are contradictory data regarding the potential association of CMB burden with the risk of symptomatic intracerebral hemorrhage (sICH) in patients with acute ischemic stroke (AIS) treated with intravenous thrombolysis (IVT). OBJECTIVE To investigate the association of high CMB burden (>10 CMBs on a pre-IVT magnetic image resonance [MRI] scan) with the risk of sICH following IVT for AIS. DATA SOURCES Eligible studies were identified by searching Medline and Scopus databases. No language or other restrictions were imposed. The literature search was conducted on October 7, 2015. This meta-analysis has adopted the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was written according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) proposal. STUDY SELECTION Eligible prospective study protocols that reported sICH rates in patients with AIS who underwent MRI for CMB screening prior to IVT. DATA EXTRACTION AND SYNTHESIS The reported rates of sICH complicating IVT in patients with AIS with pretreatment MRIwere extracted independently for groups of patients with 0 CMBs (CMB absence), 1 or more CMBs (CMB presence), 1 to 10 CMBs (lowto moderate CMB burden), and more than 10 CMBs (high CMB burden). An individual-patient data meta-analysiswas also performed in the included studies that provided complete patient data sets. MAIN OUTCOMES AND MEASURES Symptomatic intracerebral hemorrhage based on the European Cooperative Acute Stroke Study-II definition (any intracranial bleed with≥4 points worsening on the National Institutes of Health Stroke Scale score). RESULTS We included 9 studies comprising 2479 patients with AIS. The risk of sICH after IVT was found to be higher in patients with evidence of CMB presence, compared with patients without CMBs (risk ratio [RR], 2.36; 95{\%}CI, 1.21-4.61; P = .01). A higher risk for sICH after IVT was detected in patients with high CMB burden (>10 CMBs) when compared with patients with 0 to 10 CMBs (RR, 12.10; 95{\%}CI, 4.36-33.57; P < .001) or 1 to 10 CMBs (RR, 7.01; 95{\%}CI, 3.20-15.38; P < .001) on pretreatment MRI. In the individual-patient data meta-analysis, high CMB burden was associated with increased likelihood of sICH before (unadjusted odds ratio, 31.06; 95{\%}CI, 7.12-135.44; P < .001) and after (adjusted odds ratio, 18.17; 95{\%}CI, 2.39-138.22; P = .005) adjusting for potential confounders. CONCLUSIONS AND RELEVANCE Presence ofCMBand highCMBburdens on pretreatment MRI were independently associated with sICH in patients with AIS treated with IVT. High CMB burden may be included in individual risk stratification scores predicting sICH risk following IVT for AIS.",
author = "Georgios Tsivgoulis and Ramin Zand and Katsanos, {Aristeidis H.} and Guillaume Turc and Nolte, {Christian H.} and Simon Jung and Charlotte Cordonnier and Fiebach, {Jochen B.} and Scheitz, {Jan F.} and Klinger-Gratz, {Pascal P.} and Catherine Oppenheim and Nitin Goyal and Apostolos Safouris and Mattle, {Heinrich P.} and Anne Alexandrov and Schellinger, {Peter D.} and Andrei Alexandrov",
year = "2016",
month = "6",
day = "1",
doi = "10.1001/jamaneurol.2016.0292",
language = "English (US)",
volume = "73",
pages = "675--683",
journal = "JAMA Neurology",
issn = "2168-6149",
publisher = "American Medical Association",
number = "6",

}

TY - JOUR

T1 - Risk of symptomatic intracerebral hemorrhage after intravenous thrombolysis in patients with acute ischemic stroke and high cerebral microbleed burden ameta-analysis

AU - Tsivgoulis, Georgios

AU - Zand, Ramin

AU - Katsanos, Aristeidis H.

AU - Turc, Guillaume

AU - Nolte, Christian H.

AU - Jung, Simon

AU - Cordonnier, Charlotte

AU - Fiebach, Jochen B.

AU - Scheitz, Jan F.

AU - Klinger-Gratz, Pascal P.

AU - Oppenheim, Catherine

AU - Goyal, Nitin

AU - Safouris, Apostolos

AU - Mattle, Heinrich P.

AU - Alexandrov, Anne

AU - Schellinger, Peter D.

AU - Alexandrov, Andrei

PY - 2016/6/1

Y1 - 2016/6/1

N2 - IMPORTANCE Cerebral microbleeds (CMBs) have been established as an independent predictor of cerebral bleeding. There are contradictory data regarding the potential association of CMB burden with the risk of symptomatic intracerebral hemorrhage (sICH) in patients with acute ischemic stroke (AIS) treated with intravenous thrombolysis (IVT). OBJECTIVE To investigate the association of high CMB burden (>10 CMBs on a pre-IVT magnetic image resonance [MRI] scan) with the risk of sICH following IVT for AIS. DATA SOURCES Eligible studies were identified by searching Medline and Scopus databases. No language or other restrictions were imposed. The literature search was conducted on October 7, 2015. This meta-analysis has adopted the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was written according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) proposal. STUDY SELECTION Eligible prospective study protocols that reported sICH rates in patients with AIS who underwent MRI for CMB screening prior to IVT. DATA EXTRACTION AND SYNTHESIS The reported rates of sICH complicating IVT in patients with AIS with pretreatment MRIwere extracted independently for groups of patients with 0 CMBs (CMB absence), 1 or more CMBs (CMB presence), 1 to 10 CMBs (lowto moderate CMB burden), and more than 10 CMBs (high CMB burden). An individual-patient data meta-analysiswas also performed in the included studies that provided complete patient data sets. MAIN OUTCOMES AND MEASURES Symptomatic intracerebral hemorrhage based on the European Cooperative Acute Stroke Study-II definition (any intracranial bleed with≥4 points worsening on the National Institutes of Health Stroke Scale score). RESULTS We included 9 studies comprising 2479 patients with AIS. The risk of sICH after IVT was found to be higher in patients with evidence of CMB presence, compared with patients without CMBs (risk ratio [RR], 2.36; 95%CI, 1.21-4.61; P = .01). A higher risk for sICH after IVT was detected in patients with high CMB burden (>10 CMBs) when compared with patients with 0 to 10 CMBs (RR, 12.10; 95%CI, 4.36-33.57; P < .001) or 1 to 10 CMBs (RR, 7.01; 95%CI, 3.20-15.38; P < .001) on pretreatment MRI. In the individual-patient data meta-analysis, high CMB burden was associated with increased likelihood of sICH before (unadjusted odds ratio, 31.06; 95%CI, 7.12-135.44; P < .001) and after (adjusted odds ratio, 18.17; 95%CI, 2.39-138.22; P = .005) adjusting for potential confounders. CONCLUSIONS AND RELEVANCE Presence ofCMBand highCMBburdens on pretreatment MRI were independently associated with sICH in patients with AIS treated with IVT. High CMB burden may be included in individual risk stratification scores predicting sICH risk following IVT for AIS.

AB - IMPORTANCE Cerebral microbleeds (CMBs) have been established as an independent predictor of cerebral bleeding. There are contradictory data regarding the potential association of CMB burden with the risk of symptomatic intracerebral hemorrhage (sICH) in patients with acute ischemic stroke (AIS) treated with intravenous thrombolysis (IVT). OBJECTIVE To investigate the association of high CMB burden (>10 CMBs on a pre-IVT magnetic image resonance [MRI] scan) with the risk of sICH following IVT for AIS. DATA SOURCES Eligible studies were identified by searching Medline and Scopus databases. No language or other restrictions were imposed. The literature search was conducted on October 7, 2015. This meta-analysis has adopted the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was written according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) proposal. STUDY SELECTION Eligible prospective study protocols that reported sICH rates in patients with AIS who underwent MRI for CMB screening prior to IVT. DATA EXTRACTION AND SYNTHESIS The reported rates of sICH complicating IVT in patients with AIS with pretreatment MRIwere extracted independently for groups of patients with 0 CMBs (CMB absence), 1 or more CMBs (CMB presence), 1 to 10 CMBs (lowto moderate CMB burden), and more than 10 CMBs (high CMB burden). An individual-patient data meta-analysiswas also performed in the included studies that provided complete patient data sets. MAIN OUTCOMES AND MEASURES Symptomatic intracerebral hemorrhage based on the European Cooperative Acute Stroke Study-II definition (any intracranial bleed with≥4 points worsening on the National Institutes of Health Stroke Scale score). RESULTS We included 9 studies comprising 2479 patients with AIS. The risk of sICH after IVT was found to be higher in patients with evidence of CMB presence, compared with patients without CMBs (risk ratio [RR], 2.36; 95%CI, 1.21-4.61; P = .01). A higher risk for sICH after IVT was detected in patients with high CMB burden (>10 CMBs) when compared with patients with 0 to 10 CMBs (RR, 12.10; 95%CI, 4.36-33.57; P < .001) or 1 to 10 CMBs (RR, 7.01; 95%CI, 3.20-15.38; P < .001) on pretreatment MRI. In the individual-patient data meta-analysis, high CMB burden was associated with increased likelihood of sICH before (unadjusted odds ratio, 31.06; 95%CI, 7.12-135.44; P < .001) and after (adjusted odds ratio, 18.17; 95%CI, 2.39-138.22; P = .005) adjusting for potential confounders. CONCLUSIONS AND RELEVANCE Presence ofCMBand highCMBburdens on pretreatment MRI were independently associated with sICH in patients with AIS treated with IVT. High CMB burden may be included in individual risk stratification scores predicting sICH risk following IVT for AIS.

UR - http://www.scopus.com/inward/record.url?scp=84974625093&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84974625093&partnerID=8YFLogxK

U2 - 10.1001/jamaneurol.2016.0292

DO - 10.1001/jamaneurol.2016.0292

M3 - Article

VL - 73

SP - 675

EP - 683

JO - JAMA Neurology

JF - JAMA Neurology

SN - 2168-6149

IS - 6

ER -