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Diffusion-weighted imaging lesions and risk of recurrent stroke after intracerebral haemorrhage
  1. Kim Wiegertjes1,
  2. Lynn Dinsmore2,
  3. Jonathan Drever2,
  4. Aidan Hutchison2,
  5. Jacqueline Stephen3,
  6. Maria C Valdés Hernández2,4,5,
  7. Priya Bhatnagar6,
  8. David P Minks6,
  9. Mark A Rodrigues2,5,
  10. David J Werring7,
  11. Frank-Erik de Leeuw1,
  12. Catharina JM Klijn1,
  13. Rustam Al-Shahi Salman2,3,
  14. Phillip M White8,
  15. Joanna M Wardlaw2,4,5,9
  1. 1 Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands
  2. 2 Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, UK
  3. 3 Edinburgh Clinical Trials Unit, Usher Institute, The University of Edinburgh, Edinburgh, UK
  4. 4 Row Fogo Centre for Research into Ageing and the Brain, The University of Edinburgh, Edinburgh, UK
  5. 5 Edinburgh Imaging, The University of Edinburgh, Edinburgh, UK
  6. 6 Department of Neuroradiology, Newcastle-upon-Tyne Hospitals NHS Trust, Newcastle-upon-Tyne, UK
  7. 7 Stroke Research Centre, Queen Square Institute of Neurology, University College London, London, UK
  8. 8 Translational and Clinical Research Institute, The University of Newcastle, Newcastle-upon-Tyne, UK
  9. 9 Dementia Research Institute, The University of Edinburgh, Edinburgh, UK
  1. Correspondence to Professor Rustam Al-Shahi Salman, The University of Edinburgh Centre for Clinical Brain Sciences, Edinburgh, UK; rustam.al-shahi{at}ed.ac.uk

Abstract

Objective To determine whether the presence of diffusion-weighted imaging-positive (DWI+) lesions is associated with recurrent stroke after intracerebral haemorrhage (ICH).

Methods The REstart or STop Antithrombotics Randomised Trial (RESTART) assessed the effect of restarting versus avoiding antiplatelet therapy after ICH on major vascular events for up to 5 years. We rated DWI sequences of MRI done before randomisation for DWI+ lesion presence, masked to outcome and antiplatelet use. Cox proportional hazards regression models were used to quantify associations.

Results Of 537 participants in RESTART, 247 (median (IQR) age 75.7 (69.6–81.1) years; 170 men (68.8%); 120 started vs 127 avoided antiplatelet therapy) had DWI sequences on brain MRI at a median of 57 days (IQR 19–103) after ICH, of whom 73 (30%) had one or more DWI+ lesion. During a median follow-up of 2 years (1–3), 18 participants had recurrent ICH and 21 had ischaemic stroke. DWI+ lesion presence was associated with all stroke, (adjusted HR 2.2 (95% CI 1.1 to 4.2)) and recurrent ICH (4.8 (95% CI 1.8 to 13.2)), but not ischaemic stroke (0.9 (95% CI 0.3 to 2.5)). DWI+ lesion presence (0.5 (95% CI 0.2 to 1.3)) vs absence (0.6 (95% CI 0.3 to 1.5), pinteraction=0.66) did not modify the effect of antiplatelet therapy on a composite outcome of recurrent stroke.

Conclusions DWI+ lesion presence in ICH survivors is associated with recurrent ICH, but not with ischaemic stroke. We found no evidence of modification of effects of antiplatelet therapy on recurrent stroke after ICH by DWI+ lesion presence. These findings provide a new perspective on the significance of DWI+ lesions, which may be markers of microvascular mechanisms associated with recurrent ICH.

Trial registration number ISRCTN71907627.

Data availability statement

Data are available upon reasonable request. An anonymised version of the RESTART data set will be available from 22 May 2020 (1 year after publication of the primary findings), upon request to the members of the RESTART trial steering committee by using the online data request form (https://www.research.ed.ac.uk/portal/en/datasets/restart-data-request-form(54c98845-fdbc-45ea-a5fc-495df837ad25).html).

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Data availability statement

Data are available upon reasonable request. An anonymised version of the RESTART data set will be available from 22 May 2020 (1 year after publication of the primary findings), upon request to the members of the RESTART trial steering committee by using the online data request form (https://www.research.ed.ac.uk/portal/en/datasets/restart-data-request-form(54c98845-fdbc-45ea-a5fc-495df837ad25).html).

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Footnotes

  • Twitter @BleedingStroke

  • Contributors RA-SS (chief investigator), PW and DJW obtained funding for RESTART. RA-SS, PW and JW designed the imaging substudy of RESTART, and realised and managed the imaging data collection and rating. PW, DPM, MR and PB performed imaging assessments in RESTART. KW assessed diffusion-weighted imaging sequences for these analyses. LD, JD and AH assisted with data collection. JW informed on methods and contributed to the design of the imaging assessment, advised on and supported the acquisition, collection, management, assessment, rating, analysis and interpretation of the imaging data. KW, JS, MdCVH, RA-SS, PW and JW contributed to data analysis and interpretation. KW, RA-SS, F-EdL, CJMK and JW drafted the report. All authors commented on drafts and approved the final version. KW, RA-SS, JS, and JW had full access to all the data.

  • Competing interests MdCVH and JW are supported by the Row Fogo Charitable Trust who funds the Row Fogo Charitable Trust Centre for Research into the Ageing and the Brain Re No: AD.ROW4.35.BRO-D.FID 3668413. DJW reports personal fees from Bayer and JFB Consulting, outside the submitted work (no award/grant number). F-EdL was supported by a clinical established investigator grant of the Dutch Heart Foundation (grant 2014T060), and by a VIDI innovational grant from The Netherlands Organisation for Health Research and Development, ZonMw (grant 016126351). CJMK is supported by a clinical established investigator grant of the Dutch Heart Foundation (grant no. 2012 T077) and an Aspasia grant from The Netherlands Organization for Health Research and Development (ZonMw grant no. 015.008.048). RA-SS reports a grant from the British Heart Foundation (SP/12/2/29422) paid to the University of Edinburgh for the conduct of RESTART, and grants from the Stroke Association, Chest Heart and Stroke Scotland and GE Healthcare Limited, outside the submitted work (no award/grant number). PW reports personal fees from Stryker Global Advisory Board on Hemorrhagic Stroke and MicroVention-Terumo, and a grant from MicroVention-Terumo outside the submitted work (no award/grant number). JW is supported by European Union Horizon 2020, PHC-03-15, project No 666881, ‘SVDs@Target’, Fondation Leducq Transatlantic Network of Excellence for the Study of Perivascular Spaces in Small Vessel Disease, ref no. 16 CVD 05, the UK Dementia Research Institute which receives its funding from DRI, funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK, and by grants from the EU Framework 7, Medical Research Council and the British Heart Foundation, outside the submitted work (no award/grant number).

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

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