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.
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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.