Article Text

Download PDFPDF
Short report
Circadian rhythm of ischaemic core progression in human stroke
  1. Paul Reidler1,
  2. Alex Brehm2,
  3. Peter B. Sporns2,3,
  4. Vanessa Granja Burbano4,
  5. Lena Stueckelschweiger1,
  6. Gabriel Broocks3,
  7. Thomas Liebig5,
  8. Marios-Nikos Psychogios2,
  9. Jens Ricke1,
  10. Konstantinos Dimitriadis4,6,
  11. Martin Dichgans4,7,8,
  12. Wolfgang G. Kunz1,
  13. Steffen Tiedt4,8
  1. 1Department of Radiology, University Hospital, LMU Munich, Munich, Germany
  2. 2Department of Neuroradiology, Clinic for Radiology & Nuclear Medicine, University Hospital Basel, Basel, Switzerland
  3. 3Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  4. 4Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany
  5. 5Institute of Neuroradiology, University Hospital, LMU Munich, Munich, Germany
  6. 6Department of Neurology, University Hospital, LMU Munich, Munich, Germany
  7. 7SyNergy, Munich Cluster for Systems Neurology, Munich, Germany
  8. 8Consortium International pour la Recherche Circadienne sur l'AVC (CIRCA), Munich, Germany
  1. Correspondence to Dr Steffen Tiedt, Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany; steffen.tiedt{at}


Introduction Experimental stroke studies suggest an influence of the time of day of stroke onset on infarct progression. Whether this holds true after human stroke is unknown, but would have implications for the design of randomised controlled trials, especially those on neuroprotection.

Methods We pooled data from 583 patients with anterior large-vessel occlusion stroke from three prospectively recruited cohorts. Ischaemic core and penumbra volumes were determined with CT perfusion using automated thresholds. Core growth was calculated as the ratio of core volume and onset-to-imaging time. To determine circadian rhythmicity, we applied multivariable linear and sinusoidal regression analysis adjusting for potential baseline confounders.

Results Patients with symptom onset at night showed larger ischaemic core volumes on admission compared with patients with onset during the day (median, 40.2 mL vs 33.8 mL), also in adjusted analyses (p=0.008). Sinusoidal analysis indicated a peak of core volumes with onset at 11pm. Core growth was faster at night compared with day onset (adjusted p=0.01), especially for shorter onset-to-imaging times. In contrast, penumbra volumes did not change across the 24-hour cycle.

Discussion These results suggest that human infarct progression varies across the 24-hour cycle with potential implications for the design and interpretation of neuroprotection trials.

  • stroke

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Twitter @SteffenTiedt

  • Correction notice This article has been corrected since it appeared Online First. Contributor statement has been updated for minor changes.

  • Contributors Significant contribution to: conception and design of the study (PR, WGK, ST), acquisition and analysis of data (PR, AB, PBS, VGB, LS, GB, TL, MNP, JR, KD, MD, WGK and ST), participation in drafting a significant portion of the manuscript or figures (PR, WGK and ST). All authors approved the final version of the manuscript. PR and AB contributed equally to this paper.

  • Funding ST was supported by a grant from the Corona foundation.

  • Competing interests TL reports personal fees from Stryker, Medtronic, Acandis, Cerus, Phenox, Pfizer and Microvention, all outside the submitted work. All other authors declare no competing interests.

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