Georgios Tsivgoulis1, Ramin Zand2, Aristeidis H Katsanos3, Guillaume Turc4, Christian H Nolte5, Simon Jung6, Charlotte Cordonnier7, Jochen B Fiebach5, Jan F Scheitz5, Pascal P Klinger-Gratz8, Catherine Oppenheim9, Nitin Goyal2, Apostolos Safouris10, Heinrich P Mattle11, Anne W Alexandrov12, Peter D Schellinger13, Andrei V Alexandrov2. 1. Department of Neurology, The University of Tennessee Health Science Center, Memphis2Second Department of Neurology, Attikon Hospital, School of Medicine, University of Athens, Athens, Greece3International Clinical Research Center, Department of Neurology. 2. Department of Neurology, The University of Tennessee Health Science Center, Memphis. 3. Second Department of Neurology, Attikon Hospital, School of Medicine, University of Athens, Athens, Greece4Department of Neurology, University of Ioannina School of Medicine, Ioannina, Greece. 4. Department of Neurology, Hôpital Sainte-Anne, Université Paris Descartes, Sorbonne Paris Cité, Inserm UMR S894, Départements Hospitalo-Universitaires Neurovasc, Paris, France. 5. Klinik und Hochschulambulanz für Neurologie and Center for Stroke Research, Charité-Universitätsmedizin Berlin, Berlin, Germany. 6. Department of Diagnostic and Interventional Neuroradiology, Inselspital, University Hospital Bern, University of Bern, Bern, Switzerland8Department of Neurology, Inselspital, University Hospital Bern, University of Bern, Bern, Switzerland. 7. University Lille, Inserm, Centre Hospitalier Régional Universitaire de Lille, U1171, Degenerative and Vascular Cognitive Disorders, Lille, France. 8. Department of Diagnostic and Interventional Neuroradiology, Inselspital, University Hospital Bern, University of Bern, Bern, Switzerland. 9. Department of Radiology, Hôpital Sainte-Anne, Université Paris Descartes, Sorbonne Paris Cité, Inserm UMR S894, Départements Hospitalo-Universitaires Neurovasc, Paris, France. 10. Second Department of Neurology, Attikon Hospital, School of Medicine, University of Athens, Athens, Greece11Acute Stroke Unit, Metropolitan Hospital, Piraeus, Greece. 11. Department of Neurology, Inselspital, University Hospital Bern, University of Bern, Bern, Switzerland. 12. Department of Neurology, The University of Tennessee Health Science Center, Memphis12Australian Catholic University, Sydney, Australia. 13. Departments of Neurology and Neurogeriatry, Johannes Wesling Medical Center, Minden, Germany.
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 MRI were extracted independently for groups of patients with 0 CMBs (CMB absence), 1 or more CMBs (CMB presence), 1 to 10 CMBs (low to moderate CMB burden), and more than 10 CMBs (high CMB burden). An individual-patient data meta-analysis was 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 of CMB and high CMB burdens 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.
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 MRI were extracted independently for groups of patients with 0 CMBs (CMB absence), 1 or more CMBs (CMB presence), 1 to 10 CMBs (low to moderate CMB burden), and more than 10 CMBs (high CMB burden). An individual-patient data meta-analysis was 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 of CMB and high CMB burdens 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.
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