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, Chelsea S.
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.
N1 - Funding Information:
Dr Albers has undertaken consultancy for iSchemaView, with an equity interest and consultancy for Medtronic. Dr Cordonnier is a member of the Institut Universitaire de France. Dr Nolte received funding from the German Federal Ministry of Education and Research via the grant Center for Stroke Research Berlin (01 EO 0801). Dr Scheitz participates in the Charité Clinical Scientist Program funded by the Charité Universitätsmedizin Berlin and the Berlin Institute of Health. Dr Saver has consulted on stroke prevention clinical trial design and conduct for Boehringer Ingelheim. Dr Werring has received funding from Bayer, Allergan, and Ixico. This work was partly undertaken at University College London Hospitals/University College London
Funding Information:
who received a proportion of funding from the Department of Health’s National Institute of Health Research Biomedical Research Centers funding scheme. The other authors report no conflicts.
Funding Information:
Dr Albers has undertaken consultancy for iSchemaView, with an equity interest and consultancy for Medtronic. Dr Cordonnier is a member of the Institut Universitaire de France. Dr Nolte received funding from the German Federal Ministry of Education and Research via the grant Center for Stroke Research Berlin (01 EO 0801). Dr Scheitz participates in the Charité Clinical Scientist Program funded by the Charité Universitätsmedizin Berlin and the Berlin Institute of Health. Dr Saver has consulted on stroke prevention clinical trial design and conduct for Boehringer Ingelheim. Dr Werring has received funding from Bayer, Allergan, and Ixico.
Publisher Copyright:
© 2017 American Heart Association, Inc.
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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U2 - 10.1161/STROKEAHA.116.012992
DO - 10.1161/STROKEAHA.116.012992
M3 - Article
C2 - 28720659
AN - SCOPUS:85025141540
VL - 48
SP - 2084
EP - 2090
JO - Stroke
JF - Stroke
SN - 0039-2499
IS - 8
ER -