title: Effect of alteplase on the CT hyperdense artery sign and outcome after ischemic stroke.
abstract: OBJECTIVE
  To investigate whether the location and extent of the CT hyperdense artery sign (HAS) at presentation affects response to IV alteplase in the randomized controlled Third International Stroke Trial (IST-3).
  
  
  METHODS
  All prerandomization and follow-up (24-48 hours) CT brain scans in IST-3 were assessed for HAS presence, location, and extent by masked raters. We assessed whether HAS grew, persisted, shrank, or disappeared at follow-up, the association with 6-month functional outcome, and effect of alteplase. IST-3 is registered (ISRCTN25765518).
  
  
  RESULTS
  HAS presence (vs absence) independently predicted poor 6-month outcome (increased Oxford Handicap Scale [OHS]) on adjusted ordinal regression analysis (odds ratio [OR] 0.66, p < 0.001). Outcome was worse in patients with more (vs less) extensive HAS (OR 0.61, p = 0.027) but not in proximal (vs distal) HAS (p = 0.420). Increasing age was associated with more HAS growth at follow-up (OR 1.01, p = 0.013). Treatment with alteplase increased HAS shrinkage/disappearance at follow-up (OR 0.77, p = 0.006). There was no significant difference in HAS shrinkage with alteplase in proximal (vs distal) or more (vs less) extensive HAS (p = 0.516 and p = 0.580, respectively). There was no interaction between presence vs absence of HAS and benefit of alteplase on 6-month OHS (p = 0.167).
  
  
  CONCLUSIONS
  IV alteplase promotes measurable reduction in HAS regardless of HAS location or extent. Alteplase increased independence at 6 months in patients with and without HAS.
  
  
  METHODS
  This study provides Class I evidence that for patients within 6 hours of ischemic stroke with a CT hyperdense artery sign, IV alteplase reduced intra-arterial hyperdense thrombus.
authors.affiliation: From the Division of Neuroimaging Sciences (G.M., Z.M., A.J.F., G.C., J.M.W.) and the Division of Clinical Neurosciences (P.A.G.S.), University of Edinburgh, UK; the Department of Neuroradiology (R.v.K.), Dresden University Stroke Centre, Germany; Danderyd Hospital (A.v.H.), Stockholm, Sweden; Neuroradiology (N.B.), James Cook University Hospital, Middlesborough, UK; School of Pathology and Laboratory Medicine (L.C.), University of Western Australia, Perth; Cliniques Universitaires St Luc (A.P.), Neurologie, Belgium; Stroke Center (A.A.), Sacro Cuore-Don Calabria Hospital, Negrar, Italy; the Department of Neuroradiology (G.P.), Salford Royal NHS Foundation Trust, Manchester, UK; and the Westmead Hospital Clinical School and The George Institute for Global Health (R.I.L.), University of Sydney, Australia.
authors.forename: Grant
authors.initials: G
authors.lastname: Mair
authors.affiliation: From the Division of Neuroimaging Sciences (G.M., Z.M., A.J.F., G.C., J.M.W.) and the Division of Clinical Neurosciences (P.A.G.S.), University of Edinburgh, UK; the Department of Neuroradiology (R.v.K.), Dresden University Stroke Centre, Germany; Danderyd Hospital (A.v.H.), Stockholm, Sweden; Neuroradiology (N.B.), James Cook University Hospital, Middlesborough, UK; School of Pathology and Laboratory Medicine (L.C.), University of Western Australia, Perth; Cliniques Universitaires St Luc (A.P.), Neurologie, Belgium; Stroke Center (A.A.), Sacro Cuore-Don Calabria Hospital, Negrar, Italy; the Department of Neuroradiology (G.P.), Salford Royal NHS Foundation Trust, Manchester, UK; and the Westmead Hospital Clinical School and The George Institute for Global Health (R.I.L.), University of Sydney, Australia.
authors.forename: Rüdiger
authors.initials: R
authors.lastname: von Kummer
authors.affiliation: From the Division of Neuroimaging Sciences (G.M., Z.M., A.J.F., G.C., J.M.W.) and the Division of Clinical Neurosciences (P.A.G.S.), University of Edinburgh, UK; the Department of Neuroradiology (R.v.K.), Dresden University Stroke Centre, Germany; Danderyd Hospital (A.v.H.), Stockholm, Sweden; Neuroradiology (N.B.), James Cook University Hospital, Middlesborough, UK; School of Pathology and Laboratory Medicine (L.C.), University of Western Australia, Perth; Cliniques Universitaires St Luc (A.P.), Neurologie, Belgium; Stroke Center (A.A.), Sacro Cuore-Don Calabria Hospital, Negrar, Italy; the Department of Neuroradiology (G.P.), Salford Royal NHS Foundation Trust, Manchester, UK; and the Westmead Hospital Clinical School and The George Institute for Global Health (R.I.L.), University of Sydney, Australia.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Morris
authors.affiliation: From the Division of Neuroimaging Sciences (G.M., Z.M., A.J.F., G.C., J.M.W.) and the Division of Clinical Neurosciences (P.A.G.S.), University of Edinburgh, UK; the Department of Neuroradiology (R.v.K.), Dresden University Stroke Centre, Germany; Danderyd Hospital (A.v.H.), Stockholm, Sweden; Neuroradiology (N.B.), James Cook University Hospital, Middlesborough, UK; School of Pathology and Laboratory Medicine (L.C.), University of Western Australia, Perth; Cliniques Universitaires St Luc (A.P.), Neurologie, Belgium; Stroke Center (A.A.), Sacro Cuore-Don Calabria Hospital, Negrar, Italy; the Department of Neuroradiology (G.P.), Salford Royal NHS Foundation Trust, Manchester, UK; and the Westmead Hospital Clinical School and The George Institute for Global Health (R.I.L.), University of Sydney, Australia.
authors.forename: Anders
authors.initials: A
authors.lastname: von Heijne
authors.affiliation: From the Division of Neuroimaging Sciences (G.M., Z.M., A.J.F., G.C., J.M.W.) and the Division of Clinical Neurosciences (P.A.G.S.), University of Edinburgh, UK; the Department of Neuroradiology (R.v.K.), Dresden University Stroke Centre, Germany; Danderyd Hospital (A.v.H.), Stockholm, Sweden; Neuroradiology (N.B.), James Cook University Hospital, Middlesborough, UK; School of Pathology and Laboratory Medicine (L.C.), University of Western Australia, Perth; Cliniques Universitaires St Luc (A.P.), Neurologie, Belgium; Stroke Center (A.A.), Sacro Cuore-Don Calabria Hospital, Negrar, Italy; the Department of Neuroradiology (G.P.), Salford Royal NHS Foundation Trust, Manchester, UK; and the Westmead Hospital Clinical School and The George Institute for Global Health (R.I.L.), University of Sydney, Australia.
authors.forename: Nick
authors.initials: N
authors.lastname: Bradey
authors.affiliation: From the Division of Neuroimaging Sciences (G.M., Z.M., A.J.F., G.C., J.M.W.) and the Division of Clinical Neurosciences (P.A.G.S.), University of Edinburgh, UK; the Department of Neuroradiology (R.v.K.), Dresden University Stroke Centre, Germany; Danderyd Hospital (A.v.H.), Stockholm, Sweden; Neuroradiology (N.B.), James Cook University Hospital, Middlesborough, UK; School of Pathology and Laboratory Medicine (L.C.), University of Western Australia, Perth; Cliniques Universitaires St Luc (A.P.), Neurologie, Belgium; Stroke Center (A.A.), Sacro Cuore-Don Calabria Hospital, Negrar, Italy; the Department of Neuroradiology (G.P.), Salford Royal NHS Foundation Trust, Manchester, UK; and the Westmead Hospital Clinical School and The George Institute for Global Health (R.I.L.), University of Sydney, Australia.
authors.forename: Lesley
authors.initials: L
authors.lastname: Cala
authors.affiliation: From the Division of Neuroimaging Sciences (G.M., Z.M., A.J.F., G.C., J.M.W.) and the Division of Clinical Neurosciences (P.A.G.S.), University of Edinburgh, UK; the Department of Neuroradiology (R.v.K.), Dresden University Stroke Centre, Germany; Danderyd Hospital (A.v.H.), Stockholm, Sweden; Neuroradiology (N.B.), James Cook University Hospital, Middlesborough, UK; School of Pathology and Laboratory Medicine (L.C.), University of Western Australia, Perth; Cliniques Universitaires St Luc (A.P.), Neurologie, Belgium; Stroke Center (A.A.), Sacro Cuore-Don Calabria Hospital, Negrar, Italy; the Department of Neuroradiology (G.P.), Salford Royal NHS Foundation Trust, Manchester, UK; and the Westmead Hospital Clinical School and The George Institute for Global Health (R.I.L.), University of Sydney, Australia.
authors.forename: André
authors.initials: A
authors.lastname: Peeters
authors.affiliation: From the Division of Neuroimaging Sciences (G.M., Z.M., A.J.F., G.C., J.M.W.) and the Division of Clinical Neurosciences (P.A.G.S.), University of Edinburgh, UK; the Department of Neuroradiology (R.v.K.), Dresden University Stroke Centre, Germany; Danderyd Hospital (A.v.H.), Stockholm, Sweden; Neuroradiology (N.B.), James Cook University Hospital, Middlesborough, UK; School of Pathology and Laboratory Medicine (L.C.), University of Western Australia, Perth; Cliniques Universitaires St Luc (A.P.), Neurologie, Belgium; Stroke Center (A.A.), Sacro Cuore-Don Calabria Hospital, Negrar, Italy; the Department of Neuroradiology (G.P.), Salford Royal NHS Foundation Trust, Manchester, UK; and the Westmead Hospital Clinical School and The George Institute for Global Health (R.I.L.), University of Sydney, Australia.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Farrall
authors.affiliation: From the Division of Neuroimaging Sciences (G.M., Z.M., A.J.F., G.C., J.M.W.) and the Division of Clinical Neurosciences (P.A.G.S.), University of Edinburgh, UK; the Department of Neuroradiology (R.v.K.), Dresden University Stroke Centre, Germany; Danderyd Hospital (A.v.H.), Stockholm, Sweden; Neuroradiology (N.B.), James Cook University Hospital, Middlesborough, UK; School of Pathology and Laboratory Medicine (L.C.), University of Western Australia, Perth; Cliniques Universitaires St Luc (A.P.), Neurologie, Belgium; Stroke Center (A.A.), Sacro Cuore-Don Calabria Hospital, Negrar, Italy; the Department of Neuroradiology (G.P.), Salford Royal NHS Foundation Trust, Manchester, UK; and the Westmead Hospital Clinical School and The George Institute for Global Health (R.I.L.), University of Sydney, Australia.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Adami
authors.affiliation: From the Division of Neuroimaging Sciences (G.M., Z.M., A.J.F., G.C., J.M.W.) and the Division of Clinical Neurosciences (P.A.G.S.), University of Edinburgh, UK; the Department of Neuroradiology (R.v.K.), Dresden University Stroke Centre, Germany; Danderyd Hospital (A.v.H.), Stockholm, Sweden; Neuroradiology (N.B.), James Cook University Hospital, Middlesborough, UK; School of Pathology and Laboratory Medicine (L.C.), University of Western Australia, Perth; Cliniques Universitaires St Luc (A.P.), Neurologie, Belgium; Stroke Center (A.A.), Sacro Cuore-Don Calabria Hospital, Negrar, Italy; the Department of Neuroradiology (G.P.), Salford Royal NHS Foundation Trust, Manchester, UK; and the Westmead Hospital Clinical School and The George Institute for Global Health (R.I.L.), University of Sydney, Australia.
authors.forename: Gillian
authors.initials: G
authors.lastname: Potter
authors.affiliation: From the Division of Neuroimaging Sciences (G.M., Z.M., A.J.F., G.C., J.M.W.) and the Division of Clinical Neurosciences (P.A.G.S.), University of Edinburgh, UK; the Department of Neuroradiology (R.v.K.), Dresden University Stroke Centre, Germany; Danderyd Hospital (A.v.H.), Stockholm, Sweden; Neuroradiology (N.B.), James Cook University Hospital, Middlesborough, UK; School of Pathology and Laboratory Medicine (L.C.), University of Western Australia, Perth; Cliniques Universitaires St Luc (A.P.), Neurologie, Belgium; Stroke Center (A.A.), Sacro Cuore-Don Calabria Hospital, Negrar, Italy; the Department of Neuroradiology (G.P.), Salford Royal NHS Foundation Trust, Manchester, UK; and the Westmead Hospital Clinical School and The George Institute for Global Health (R.I.L.), University of Sydney, Australia.
authors.forename: Geoff
authors.initials: G
authors.lastname: Cohen
authors.affiliation: From the Division of Neuroimaging Sciences (G.M., Z.M., A.J.F., G.C., J.M.W.) and the Division of Clinical Neurosciences (P.A.G.S.), University of Edinburgh, UK; the Department of Neuroradiology (R.v.K.), Dresden University Stroke Centre, Germany; Danderyd Hospital (A.v.H.), Stockholm, Sweden; Neuroradiology (N.B.), James Cook University Hospital, Middlesborough, UK; School of Pathology and Laboratory Medicine (L.C.), University of Western Australia, Perth; Cliniques Universitaires St Luc (A.P.), Neurologie, Belgium; Stroke Center (A.A.), Sacro Cuore-Don Calabria Hospital, Negrar, Italy; the Department of Neuroradiology (G.P.), Salford Royal NHS Foundation Trust, Manchester, UK; and the Westmead Hospital Clinical School and The George Institute for Global Health (R.I.L.), University of Sydney, Australia.
authors.forename: Peter A G
authors.initials: PA
authors.lastname: Sandercock
authors.affiliation: From the Division of Neuroimaging Sciences (G.M., Z.M., A.J.F., G.C., J.M.W.) and the Division of Clinical Neurosciences (P.A.G.S.), University of Edinburgh, UK; the Department of Neuroradiology (R.v.K.), Dresden University Stroke Centre, Germany; Danderyd Hospital (A.v.H.), Stockholm, Sweden; Neuroradiology (N.B.), James Cook University Hospital, Middlesborough, UK; School of Pathology and Laboratory Medicine (L.C.), University of Western Australia, Perth; Cliniques Universitaires St Luc (A.P.), Neurologie, Belgium; Stroke Center (A.A.), Sacro Cuore-Don Calabria Hospital, Negrar, Italy; the Department of Neuroradiology (G.P.), Salford Royal NHS Foundation Trust, Manchester, UK; and the Westmead Hospital Clinical School and The George Institute for Global Health (R.I.L.), University of Sydney, Australia.
authors.forename: Richard I
authors.initials: RI
authors.lastname: Lindley
authors.affiliation: From the Division of Neuroimaging Sciences (G.M., Z.M., A.J.F., G.C., J.M.W.) and the Division of Clinical Neurosciences (P.A.G.S.), University of Edinburgh, UK; the Department of Neuroradiology (R.v.K.), Dresden University Stroke Centre, Germany; Danderyd Hospital (A.v.H.), Stockholm, Sweden; Neuroradiology (N.B.), James Cook University Hospital, Middlesborough, UK; School of Pathology and Laboratory Medicine (L.C.), University of Western Australia, Perth; Cliniques Universitaires St Luc (A.P.), Neurologie, Belgium; Stroke Center (A.A.), Sacro Cuore-Don Calabria Hospital, Negrar, Italy; the Department of Neuroradiology (G.P.), Salford Royal NHS Foundation Trust, Manchester, UK; and the Westmead Hospital Clinical School and The George Institute for Global Health (R.I.L.), University of Sydney, Australia. joanna.wardlaw@ed.ac.uk.
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Wardlaw
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001158:Arteries / Q000473:pathology*; D002545:Brain Ischemia / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D020521:Stroke / Q000175:diagnosis / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed / Q000379:methods; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator