title: Leukoaraiosis, intracerebral hemorrhage, and functional outcome after acute stroke thrombolysis.
abstract: OBJECTIVE
  To perform a systematic review and pooled meta-analysis of published studies to assess whether the presence of leukoaraiosis on neuroimaging before treatment with thrombolysis (IV or intra-arterial) is associated with an increased risk of symptomatic intracerebral hemorrhage (sICH) or poor functional outcome.
  
  
  METHODS
  We included studies of patients with acute ischemic stroke, treated with IV or intra-arterial thrombolysis, which assessed functional outcome (3-month modified Rankin Scale [mRS]) or sICH in relation to leukoaraiosis on pretreatment neuroimaging (CT or MRI). We used random-effects models to calculate pooled relative risks (RR) of sICH and poor functional outcome (mRS ≥ 2) for any vs no leukoaraiosis (using any rating scale) and for no to mild vs moderate to severe leukoaraiosis (using the Van Swieten or Fazekas Schmidt scale).
  
  
  RESULTS
  We identified 15 studies (total n = 6,967). For sICH outcome, the RR was 1.65 (n = 5,551; 95% confidence interval [CI] 1.26-2.16,p= 0.001) with an absolute risk (AR) increase of 2.5% for any leukoaraiosis vs none. The RR was 2.4 (n = 4,192; 95% CI 1.83-3.14,p= 0.001) with an AR increase of 6.2% for moderate to severe vs no to mild leukoaraiosis. For poor functional outcome; the RR was 1.30 (n = 3,401; 95% CI 1.19-1.42,p= 0.001) with an AR increase of 15.4% for any leukoaraiosis vs none. The RR was 1.31 (n = 3,659; 95% CI 1.22-1.42,p= 0.001) with an AR increase of 17.5% for moderate to severe vs no to mild leukoaraiosis. No statistical heterogeneity was noted for any of the analyses.
  
  
  CONCLUSIONS
  Leukoaraiosis presence and severity are consistently associated with an increased risk of sICH and poor functional outcome after IV or intra-arterial thrombolysis for acute ischemic stroke.
authors.affiliation: From the Stroke Research Centre (K.K., D.W., D.J.W.), Department of Brain Repair and Rehabilitation, UCL Institute of Neurology and The National Hospital for Neurology and Neurosurgery, Queen Square, London, UK; Division of Neurology, Department of Medicine, Faculty of Medicine (K.K., N.K., S.T.), and North-Eastern Stroke Research Group (K.K., N.K., S.T.), Khon Kaen University, Thailand; UCL School of Life & Medical Sciences (F.J.), London, UK; Stroke Unit (V.P.), Department of Neurology, Careggi University Hospital, Florence, Italy; Hotchkiss Brain Institute (M.D.H.), Cumming School of Medicine, University of Calgary, Canada; Radcliffe Department of Medicine (A.M.B.), University of Oxford, John Radcliffe Hospital, UK; Department of Neurology (S.J., H.P.M.), Inselspital, University of Bern, Switzerland; and Departments of Neurology and Psychiatry (N.H.), University of Massachusetts Medical School, Worcester.
authors.forename: Kannikar
authors.initials: K
authors.lastname: Kongbunkiat
authors.affiliation: From the Stroke Research Centre (K.K., D.W., D.J.W.), Department of Brain Repair and Rehabilitation, UCL Institute of Neurology and The National Hospital for Neurology and Neurosurgery, Queen Square, London, UK; Division of Neurology, Department of Medicine, Faculty of Medicine (K.K., N.K., S.T.), and North-Eastern Stroke Research Group (K.K., N.K., S.T.), Khon Kaen University, Thailand; UCL School of Life & Medical Sciences (F.J.), London, UK; Stroke Unit (V.P.), Department of Neurology, Careggi University Hospital, Florence, Italy; Hotchkiss Brain Institute (M.D.H.), Cumming School of Medicine, University of Calgary, Canada; Radcliffe Department of Medicine (A.M.B.), University of Oxford, John Radcliffe Hospital, UK; Department of Neurology (S.J., H.P.M.), Inselspital, University of Bern, Switzerland; and Departments of Neurology and Psychiatry (N.H.), University of Massachusetts Medical School, Worcester.
authors.forename: Duncan
authors.initials: D
authors.lastname: Wilson
authors.affiliation: From the Stroke Research Centre (K.K., D.W., D.J.W.), Department of Brain Repair and Rehabilitation, UCL Institute of Neurology and The National Hospital for Neurology and Neurosurgery, Queen Square, London, UK; Division of Neurology, Department of Medicine, Faculty of Medicine (K.K., N.K., S.T.), and North-Eastern Stroke Research Group (K.K., N.K., S.T.), Khon Kaen University, Thailand; UCL School of Life & Medical Sciences (F.J.), London, UK; Stroke Unit (V.P.), Department of Neurology, Careggi University Hospital, Florence, Italy; Hotchkiss Brain Institute (M.D.H.), Cumming School of Medicine, University of Calgary, Canada; Radcliffe Department of Medicine (A.M.B.), University of Oxford, John Radcliffe Hospital, UK; Department of Neurology (S.J., H.P.M.), Inselspital, University of Bern, Switzerland; and Departments of Neurology and Psychiatry (N.H.), University of Massachusetts Medical School, Worcester.
authors.forename: Narongrit
authors.initials: N
authors.lastname: Kasemsap
authors.affiliation: From the Stroke Research Centre (K.K., D.W., D.J.W.), Department of Brain Repair and Rehabilitation, UCL Institute of Neurology and The National Hospital for Neurology and Neurosurgery, Queen Square, London, UK; Division of Neurology, Department of Medicine, Faculty of Medicine (K.K., N.K., S.T.), and North-Eastern Stroke Research Group (K.K., N.K., S.T.), Khon Kaen University, Thailand; UCL School of Life & Medical Sciences (F.J.), London, UK; Stroke Unit (V.P.), Department of Neurology, Careggi University Hospital, Florence, Italy; Hotchkiss Brain Institute (M.D.H.), Cumming School of Medicine, University of Calgary, Canada; Radcliffe Department of Medicine (A.M.B.), University of Oxford, John Radcliffe Hospital, UK; Department of Neurology (S.J., H.P.M.), Inselspital, University of Bern, Switzerland; and Departments of Neurology and Psychiatry (N.H.), University of Massachusetts Medical School, Worcester.
authors.forename: Somsak
authors.initials: S
authors.lastname: Tiamkao
authors.affiliation: From the Stroke Research Centre (K.K., D.W., D.J.W.), Department of Brain Repair and Rehabilitation, UCL Institute of Neurology and The National Hospital for Neurology and Neurosurgery, Queen Square, London, UK; Division of Neurology, Department of Medicine, Faculty of Medicine (K.K., N.K., S.T.), and North-Eastern Stroke Research Group (K.K., N.K., S.T.), Khon Kaen University, Thailand; UCL School of Life & Medical Sciences (F.J.), London, UK; Stroke Unit (V.P.), Department of Neurology, Careggi University Hospital, Florence, Italy; Hotchkiss Brain Institute (M.D.H.), Cumming School of Medicine, University of Calgary, Canada; Radcliffe Department of Medicine (A.M.B.), University of Oxford, John Radcliffe Hospital, UK; Department of Neurology (S.J., H.P.M.), Inselspital, University of Bern, Switzerland; and Departments of Neurology and Psychiatry (N.H.), University of Massachusetts Medical School, Worcester.
authors.forename: Fatima
authors.initials: F
authors.lastname: Jichi
authors.affiliation: From the Stroke Research Centre (K.K., D.W., D.J.W.), Department of Brain Repair and Rehabilitation, UCL Institute of Neurology and The National Hospital for Neurology and Neurosurgery, Queen Square, London, UK; Division of Neurology, Department of Medicine, Faculty of Medicine (K.K., N.K., S.T.), and North-Eastern Stroke Research Group (K.K., N.K., S.T.), Khon Kaen University, Thailand; UCL School of Life & Medical Sciences (F.J.), London, UK; Stroke Unit (V.P.), Department of Neurology, Careggi University Hospital, Florence, Italy; Hotchkiss Brain Institute (M.D.H.), Cumming School of Medicine, University of Calgary, Canada; Radcliffe Department of Medicine (A.M.B.), University of Oxford, John Radcliffe Hospital, UK; Department of Neurology (S.J., H.P.M.), Inselspital, University of Bern, Switzerland; and Departments of Neurology and Psychiatry (N.H.), University of Massachusetts Medical School, Worcester.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Palumbo
authors.affiliation: From the Stroke Research Centre (K.K., D.W., D.J.W.), Department of Brain Repair and Rehabilitation, UCL Institute of Neurology and The National Hospital for Neurology and Neurosurgery, Queen Square, London, UK; Division of Neurology, Department of Medicine, Faculty of Medicine (K.K., N.K., S.T.), and North-Eastern Stroke Research Group (K.K., N.K., S.T.), Khon Kaen University, Thailand; UCL School of Life & Medical Sciences (F.J.), London, UK; Stroke Unit (V.P.), Department of Neurology, Careggi University Hospital, Florence, Italy; Hotchkiss Brain Institute (M.D.H.), Cumming School of Medicine, University of Calgary, Canada; Radcliffe Department of Medicine (A.M.B.), University of Oxford, John Radcliffe Hospital, UK; Department of Neurology (S.J., H.P.M.), Inselspital, University of Bern, Switzerland; and Departments of Neurology and Psychiatry (N.H.), University of Massachusetts Medical School, Worcester.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Hill
authors.affiliation: From the Stroke Research Centre (K.K., D.W., D.J.W.), Department of Brain Repair and Rehabilitation, UCL Institute of Neurology and The National Hospital for Neurology and Neurosurgery, Queen Square, London, UK; Division of Neurology, Department of Medicine, Faculty of Medicine (K.K., N.K., S.T.), and North-Eastern Stroke Research Group (K.K., N.K., S.T.), Khon Kaen University, Thailand; UCL School of Life & Medical Sciences (F.J.), London, UK; Stroke Unit (V.P.), Department of Neurology, Careggi University Hospital, Florence, Italy; Hotchkiss Brain Institute (M.D.H.), Cumming School of Medicine, University of Calgary, Canada; Radcliffe Department of Medicine (A.M.B.), University of Oxford, John Radcliffe Hospital, UK; Department of Neurology (S.J., H.P.M.), Inselspital, University of Bern, Switzerland; and Departments of Neurology and Psychiatry (N.H.), University of Massachusetts Medical School, Worcester.
authors.forename: Alastair M
authors.initials: AM
authors.lastname: Buchan
authors.affiliation: From the Stroke Research Centre (K.K., D.W., D.J.W.), Department of Brain Repair and Rehabilitation, UCL Institute of Neurology and The National Hospital for Neurology and Neurosurgery, Queen Square, London, UK; Division of Neurology, Department of Medicine, Faculty of Medicine (K.K., N.K., S.T.), and North-Eastern Stroke Research Group (K.K., N.K., S.T.), Khon Kaen University, Thailand; UCL School of Life & Medical Sciences (F.J.), London, UK; Stroke Unit (V.P.), Department of Neurology, Careggi University Hospital, Florence, Italy; Hotchkiss Brain Institute (M.D.H.), Cumming School of Medicine, University of Calgary, Canada; Radcliffe Department of Medicine (A.M.B.), University of Oxford, John Radcliffe Hospital, UK; Department of Neurology (S.J., H.P.M.), Inselspital, University of Bern, Switzerland; and Departments of Neurology and Psychiatry (N.H.), University of Massachusetts Medical School, Worcester.
authors.forename: Simon
authors.initials: S
authors.lastname: Jung
authors.affiliation: From the Stroke Research Centre (K.K., D.W., D.J.W.), Department of Brain Repair and Rehabilitation, UCL Institute of Neurology and The National Hospital for Neurology and Neurosurgery, Queen Square, London, UK; Division of Neurology, Department of Medicine, Faculty of Medicine (K.K., N.K., S.T.), and North-Eastern Stroke Research Group (K.K., N.K., S.T.), Khon Kaen University, Thailand; UCL School of Life & Medical Sciences (F.J.), London, UK; Stroke Unit (V.P.), Department of Neurology, Careggi University Hospital, Florence, Italy; Hotchkiss Brain Institute (M.D.H.), Cumming School of Medicine, University of Calgary, Canada; Radcliffe Department of Medicine (A.M.B.), University of Oxford, John Radcliffe Hospital, UK; Department of Neurology (S.J., H.P.M.), Inselspital, University of Bern, Switzerland; and Departments of Neurology and Psychiatry (N.H.), University of Massachusetts Medical School, Worcester.
authors.forename: Heinrich P
authors.initials: HP
authors.lastname: Mattle
authors.affiliation: From the Stroke Research Centre (K.K., D.W., D.J.W.), Department of Brain Repair and Rehabilitation, UCL Institute of Neurology and The National Hospital for Neurology and Neurosurgery, Queen Square, London, UK; Division of Neurology, Department of Medicine, Faculty of Medicine (K.K., N.K., S.T.), and North-Eastern Stroke Research Group (K.K., N.K., S.T.), Khon Kaen University, Thailand; UCL School of Life & Medical Sciences (F.J.), London, UK; Stroke Unit (V.P.), Department of Neurology, Careggi University Hospital, Florence, Italy; Hotchkiss Brain Institute (M.D.H.), Cumming School of Medicine, University of Calgary, Canada; Radcliffe Department of Medicine (A.M.B.), University of Oxford, John Radcliffe Hospital, UK; Department of Neurology (S.J., H.P.M.), Inselspital, University of Bern, Switzerland; and Departments of Neurology and Psychiatry (N.H.), University of Massachusetts Medical School, Worcester.
authors.forename: Nils
authors.initials: N
authors.lastname: Henninger
authors.affiliation: From the Stroke Research Centre (K.K., D.W., D.J.W.), Department of Brain Repair and Rehabilitation, UCL Institute of Neurology and The National Hospital for Neurology and Neurosurgery, Queen Square, London, UK; Division of Neurology, Department of Medicine, Faculty of Medicine (K.K., N.K., S.T.), and North-Eastern Stroke Research Group (K.K., N.K., S.T.), Khon Kaen University, Thailand; UCL School of Life & Medical Sciences (F.J.), London, UK; Stroke Unit (V.P.), Department of Neurology, Careggi University Hospital, Florence, Italy; Hotchkiss Brain Institute (M.D.H.), Cumming School of Medicine, University of Calgary, Canada; Radcliffe Department of Medicine (A.M.B.), University of Oxford, John Radcliffe Hospital, UK; Department of Neurology (S.J., H.P.M.), Inselspital, University of Bern, Switzerland; and Departments of Neurology and Psychiatry (N.H.), University of Massachusetts Medical School, Worcester. d.werring@ucl.ac.uk.
authors.forename: David J
authors.initials: DJ
authors.lastname: Werring
mesh_terms: D002545:Brain Ischemia / Q000000981:diagnostic imaging / Q000188:drug therapy*; D002543:Cerebral Hemorrhage / Q000000981:diagnostic imaging / Q000209:etiology*; D006801:Humans; D049292:Leukoaraiosis / Q000150:complications* / Q000000981:diagnostic imaging; D011379:Prognosis; D012306:Risk; D020521:Stroke / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy*; D015912:Thrombolytic Therapy / Q000009:adverse effects*; D016896:Treatment Outcome