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Original research
Brain imaging abnormalities and outcome after acute ischaemic stroke: the ENCHANTED trial
  1. Candice Delcourt1,2,3,4,
  2. Xia Wang1,2,3,
  3. Zien Zhou1,5,
  4. Joanna M Wardlaw6,
  5. Grant Mair6,
  6. Thompson G Robinson7,
  7. Xiaoying Chen1,3,
  8. Sohei Yoshimura1,8,
  9. Takako Torii-Yoshimura1,9,10,
  10. Cheryl Carcel1,2,3,
  11. Zeljka Calic11,
  12. Wee Yong Tan12,
  13. Alejandra Malavera1,
  14. Craig S Anderson1,2,3,4,
  15. Richard I Lindley1,3
  1. 1 The George Institute for Global Health, Sydney, New South Wales, Australia
  2. 2 University of New South Wales, Sydney, New South Wales, Australia
  3. 3 Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia
  4. 4 Department of Neurology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
  5. 5 Radiology Department, Shanghai Jiao Tong University, Shanghai, China
  6. 6 Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, UK
  7. 7 Department of Cardiovascular Sciences, and NIHR Biomedical Research Unit for Cardiovascular Diseases, University of Leicester, Leicester, Leicestershire, UK
  8. 8 Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
  9. 9 Department of Stroke and Cerebrovascular Diseases, National Cerebral and Cardiovascular Center, Osaka, Japan
  10. 10 Department of Neurology and Neuroscience, Nagoya City University Graduate School of Medical Science, Nagoya, Japan
  11. 11 Department of Neurophysiology, Liverpool Hospital, Liverpool, New South Wales, Australia
  12. 12 Thomson Hospital Kota Damansara, Petaling Jaya, Selangor, Malaysia
  1. Correspondence to Professor Richard I Lindley, The George Institute for Global Health, Camperdown, NSW 2050, Australia; rlindley{at}georgeinstitute.org.au

Abstract

Objective To test the hypothesis that imaging signs of ‘brain frailty’ and acute ischaemia predict clinical outcomes and symptomatic intracranial haemorrhage (sICH) after thrombolysis for acute ischaemic stroke (AIS) in the alteplase dose arm of ENhanced Control of Hypertension ANd Thrombolysis strokE stuDy (ENCHANTED).

Methods Blinded assessors coded baseline images for acute ischaemic signs (presence, extent, swelling and attenuation of acute lesions; and hyperattenuated arteries) and pre-existing changes (atrophy, leucoaraiosis and old ischaemic lesions). Logistic regression models assessed associations between imaging features and death at 7 and 90 days; good recovery (modified Rankin Scale scores 0–2 at 90 days) and sICH. Data are reported with adjusted ORs and 95% CIs.

Results 2916 patients (67±13 years, National Institutes of Health Stroke Scale 8 (5–14)) were included. Visible ischaemic lesions, severe hypoattenuation, large ischaemic lesion, swelling and hyperattenuated arteries were associated with 7-day death (OR (95% CI): 1.52 (1.06 to 2.18); 1.51 (1.01 to 2.18); 2.67 (1.52 to 4.71); 1.49 (1.03 to 2.14) and 2.17 (1.48 to 3.18)) and inversely with good outcome. Severe atrophy was inversely associated with 7-day death (0.52 (0.29 to 0.96)). Atrophy (1.52 (1.08 to 2.15)) and severe leucoaraiosis (1.74 (1.20 to 2.54)) were associated with 90-day death. Hyperattenuated arteries were associated with sICH (1.71 (1.01 to 2.89)). No imaging features modified the effect of alteplase dose.

Conclusions Non-expert-defined brain imaging signs of brain frailty and acute ischaemia contribute to the prognosis of thrombolysis-treated AIS patients for sICH and mortality. However, these imaging features showed no interaction with alteplase dose.

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Footnotes

  • Contributors CD designed and conceptualised study, had a major role in the acquisition of data, analysed the data, interpreted the data, drafted the manuscript for intellectual content, revised the manuscript for intellectual content and takes responsibility for the overall content. XW analysed the data and revised the manuscript for intellectual content. ZZ designed and conceptualised study, had a major role in the acquisition of data, interpreted the data, drafted the manuscript for intellectual content and revised the manuscript for intellectual content. JMW designed and conceptualised study, interpreted the data and revised the manuscript for intellectual content. GM designed and conceptualised study, interpreted the data and revised the manuscript for intellectual content. TGR designed and conceptualised study, interpreted the data and revised the manuscript for intellectual content. XC had a major role in the acquisition of data and revised the manuscript for intellectual content. SY had a major role in the acquisition of data, revised the manuscript for intellectual content. TT-Y had a major role in the acquisition of data and revised the manuscript for intellectual content. CC had a major role in the acquisition of data and revised the manuscript for intellectual content. ZC had a major role in the acquisition of data and revised the manuscript for intellectual content. WYT had a major role in the acquisition of data and revised the manuscript for intellectual content. AM had a major role in the acquisition of data and revised the manuscript for intellectual content. CSA designed and conceptualised study, interpreted the data and revised the manuscript for intellectual content. RIL designed and conceptualised study, interpreted the data, drafted the manuscript for intellectual content, revised the manuscript for intellectual content and takes responsibility for the overall content.

  • Funding The study was supported by grants from the Stroke Association of the UK (TSA 2012/01 and 2015/01), the National Health and Medical Research Council (NHMRC) of Australia (project grant numbers 1020462 and 1101113), the Ministry of Health and the National Council for Scientific and Technological Development of Brazil (CNPQ: 467322/2014-7, 402388/2013-5), the Ministry for Health, Welfare and Family Affairs of the Republic of Korea (HI14C1985) (for the alteplase dose arm) and a research grant from Takeda to support the conduct of the study in China. The research team received the support of the National Institute for Health Research Clinical Research Network (NIHR CRN) for conduct of the trial in England, UK. CSA is a Senior Principal Research Fellow for the NHMRC. TGR is an NIHR Senior Investigator.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request. Individual de-identified participant data used in these analyses will be shared by request from any qualified investigator via the Research Office of the George Institute for Global Health, Australia.

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