title: Number of cerebral microbleeds and risk of intracerebral hemorrhage after intravenous thrombolysis.
abstract: OBJECTIVE
  Cerebral microbleeds (CMBs) are found in a substantial proportion of patients with ischemic stroke eligible for treatment with intravenous thrombolysis. Until now, there is limited data on the impact of multiple CMBs on occurrence of intracerebral hemorrhage (ICH) after intravenous thrombolysis.
  
  
  METHODS
  Between 2008 and 2013, all patients receiving MRI-based intravenous thrombolysis were identified within our prospective thrombolysis register. Number of CMBs was rated on pretreatment T2*-weighted MRI by a rater blinded to clinical data and follow-up. Outcomes of interest were occurrence of symptomatic ICH (sICH) and parenchymal hemorrhage (PH).
  
  
  RESULTS
  Among 326 included patients, 52 patients had a single CMB (16.0%), 19 had 2 to 4 CMBs (5.8%), and 10 had ≥5 CMBs (3.1%). Frequency of sICH/PH was 1.2%/5.7% in patients without CMBs, 3.8%/3.8% in patients with a single CMB, 10.5%/21.1% in patients with 2 to 4 CMBs, and 30.0%/30.0% in patients with ≥5 CMBs, respectively (each P for trend<0.01). The unadjusted odds ratio per additional CMB for sICH was 1.19 (95% confidence interval, 1.07-1.33; P<0.01) and for PH was 1.13 (95% confidence interval, 1.03-1.24; P=0.01). Compared with patients without CMBs, both patients with 2 to 4 CMBs (P=0.02/P=0.02) and patients with ≥5 CMBs (P<0.01/P<0.01) had significantly increased odds ratios for sICH and PH, whereas in patients with a single CMB, odds ratios were not significantly increased (P=0.21/P=0.59). The association of CMB burden with sICH/PH remained significant after adjustment for possible confounders (age, age-related white matter changes score, atrial fibrillation, onset-to-treatment time, prior statin use, and systolic blood pressure on admission).
  
  
  CONCLUSIONS
  Our findings indicate a higher risk of sICH and PH after intravenous thrombolysis when multiple CMBs are present, with a graded relationship to increasing baseline CMB number.
authors.affiliation: From the Klinik und Hochschulambulanz für Neurologie (S.D., J.F.S., M.R., H.E., C.H.N.), Center for Stroke Research (J.F.S., M.R., P.B., J.B.F., C.H.N.), and Excellence Cluster NeuroCure (J.F.S.), Charité-Universitätsmedizin Berlin, Berlin, Germany; Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London, United Kingdom (D.J.W.); and The National Hospital for Neurology and Neurosurgery, London, United Kingdom (D.J.W.).
authors.forename: Steffen
authors.initials: S
authors.lastname: Dannenberg
authors.affiliation: From the Klinik und Hochschulambulanz für Neurologie (S.D., J.F.S., M.R., H.E., C.H.N.), Center for Stroke Research (J.F.S., M.R., P.B., J.B.F., C.H.N.), and Excellence Cluster NeuroCure (J.F.S.), Charité-Universitätsmedizin Berlin, Berlin, Germany; Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London, United Kingdom (D.J.W.); and The National Hospital for Neurology and Neurosurgery, London, United Kingdom (D.J.W.). jan-friedrich.scheitz@charite.de.
authors.forename: Jan F
authors.initials: JF
authors.lastname: Scheitz
authors.affiliation: From the Klinik und Hochschulambulanz für Neurologie (S.D., J.F.S., M.R., H.E., C.H.N.), Center for Stroke Research (J.F.S., M.R., P.B., J.B.F., C.H.N.), and Excellence Cluster NeuroCure (J.F.S.), Charité-Universitätsmedizin Berlin, Berlin, Germany; Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London, United Kingdom (D.J.W.); and The National Hospital for Neurology and Neurosurgery, London, United Kingdom (D.J.W.).
authors.forename: Michal
authors.initials: M
authors.lastname: Rozanski
authors.affiliation: From the Klinik und Hochschulambulanz für Neurologie (S.D., J.F.S., M.R., H.E., C.H.N.), Center for Stroke Research (J.F.S., M.R., P.B., J.B.F., C.H.N.), and Excellence Cluster NeuroCure (J.F.S.), Charité-Universitätsmedizin Berlin, Berlin, Germany; Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London, United Kingdom (D.J.W.); and The National Hospital for Neurology and Neurosurgery, London, United Kingdom (D.J.W.).
authors.forename: Hebun
authors.initials: H
authors.lastname: Erdur
authors.affiliation: From the Klinik und Hochschulambulanz für Neurologie (S.D., J.F.S., M.R., H.E., C.H.N.), Center for Stroke Research (J.F.S., M.R., P.B., J.B.F., C.H.N.), and Excellence Cluster NeuroCure (J.F.S.), Charité-Universitätsmedizin Berlin, Berlin, Germany; Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London, United Kingdom (D.J.W.); and The National Hospital for Neurology and Neurosurgery, London, United Kingdom (D.J.W.).
authors.forename: Peter
authors.initials: P
authors.lastname: Brunecker
authors.affiliation: From the Klinik und Hochschulambulanz für Neurologie (S.D., J.F.S., M.R., H.E., C.H.N.), Center for Stroke Research (J.F.S., M.R., P.B., J.B.F., C.H.N.), and Excellence Cluster NeuroCure (J.F.S.), Charité-Universitätsmedizin Berlin, Berlin, Germany; Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London, United Kingdom (D.J.W.); and The National Hospital for Neurology and Neurosurgery, London, United Kingdom (D.J.W.).
authors.forename: David J
authors.initials: DJ
authors.lastname: Werring
authors.affiliation: From the Klinik und Hochschulambulanz für Neurologie (S.D., J.F.S., M.R., H.E., C.H.N.), Center for Stroke Research (J.F.S., M.R., P.B., J.B.F., C.H.N.), and Excellence Cluster NeuroCure (J.F.S.), Charité-Universitätsmedizin Berlin, Berlin, Germany; Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London, United Kingdom (D.J.W.); and The National Hospital for Neurology and Neurosurgery, London, United Kingdom (D.J.W.).
authors.forename: Jochen B
authors.initials: JB
authors.lastname: Fiebach
authors.affiliation: From the Klinik und Hochschulambulanz für Neurologie (S.D., J.F.S., M.R., H.E., C.H.N.), Center for Stroke Research (J.F.S., M.R., P.B., J.B.F., C.H.N.), and Excellence Cluster NeuroCure (J.F.S.), Charité-Universitätsmedizin Berlin, Berlin, Germany; Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London, United Kingdom (D.J.W.); and The National Hospital for Neurology and Neurosurgery, London, United Kingdom (D.J.W.).
authors.forename: Christian H
authors.initials: CH
authors.lastname: Nolte
mesh_terms: D061605:Administration, Intravenous; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000473:pathology*; D002196:Capillaries / Q000473:pathology*; D002543:Cerebral Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D008297:Male; D012306:Risk; D020521:Stroke / Q000188:drug therapy; D015912:Thrombolytic Therapy / Q000009:adverse effects*
chemical_list: D005343:Fibrinolytic Agents
keywords: cerebral hemorrhage; cerebral microbleeds; cerebral small vessel diseases; magnetic resonance imaging; stroke; thrombolytic therapy