Experimental stroke studies suggest an influence of the time of day of stroke onset on infarct progression (Esposito et al. Nature 2020). Whether this holds true after human stroke is unknown, but would have implications for the design of randomized controlled trials, especially those on neuroprotection.
We pooled data from 583 patients with anterior large-vessel occlusion stroke from three prospectively recruited cohorts. Ischemic 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 age, onset-to-imaging time, collateral score, and center.
Patients with symptom onset at night showed larger ischemic core volumes upon admission compared to 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 to day onset (adjusted p=0.01), especially for shorter onset-to-imaging times. In contrast, penumbra volumes did not change across the 24-h cycle.
These results suggest that human infarct progression varies across the 24-h cycle with potential implications for the design and interpretation of neuroprotection trials.
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