Effect of alteplase on the CT hyperdense artery sign and functional outcome after ischemic stroke

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 5 0.027) but not in proximal (vs distal) HAS (p 5 0.420). Increasing age was associated with more HAS growth at follow-up (OR 1.01, p 5 0.013). Treatment with alteplase increased HAS shrinkage/disappearance at follow-up (OR 0.77, p5 0.006). There was no significant difference in HAS shrinkage with alteplase in proximal (vs distal) or more (vs less) extensive HAS (p5 0.516 and p5 0.580, respectively). There was no interaction between presence vs absence of HAS and benefit of alteplase on 6-month OHS (p 5 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. Classification of evidence: 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. Neurology® 2016;86:1–8 GLOSSARY ACA 5 anterior cerebral artery; CI 5 confidence interval; HAS 5 hyperdense artery sign; HU 5 Hounsfield units; ICA 5 internal carotid artery; IST-3 5 Third International Stroke Trial; MCA 5 middle cerebral artery; NIHSS 5 NIH Stroke Scale; OHS5Oxford Handicap Scale;OR5 odds ratio; PCA5 posterior cerebral artery; SIRS5 Systematic Image Review System. Arterial hyperattenuation on noncontrast CT, the hyperdense artery sign (HAS), is a consistently recognized CT sign of acute ischemic stroke. HAS is highly specific and moderately sensitive for intracranial arterial obstruction by thrombus. HAS is associated with increased stroke severity at presentation and worse long-term outcomes. There are, however, limited data on how the location, extent, or persistence of HAS relates to functional outcome following stroke, and importantly whether patients with (vs without) HAS benefit differently from IV thrombolysis with alteplase. 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. Coinvestigators are listed on the Neurology® Web site at Neurology.org. Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. The Article Processing Charge was paid by the MRC. This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2015 American Academy of Neurology 1 a 2015 American Academy of Neurology. Unauthorized reproduction of this article is prohibited. Published Ahead of Print on December 9, 2015 as 10.1212/WNL.0000000000002236