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Background: Ischemic and hemorrhagic stroke onset exhibit is known to exhibit diurnal variation throughout the 24-hour cycle. But whether this variation differs on weekdays compared with weekends/holidays has not been well delineated. Methods: We evaluated consecutive patients with acute cerebral ischemia [(ACI), including ischemic stroke (IS) and transient ischemic attack (TIA)] and intraparenchymal hemorrhage (IPH) enrolled during ambulance transport to 60 receiving stroke centers in the NIH FAST-MAG trial. Enrollment required onset within the prior 2 hours, excluding confounding by wake-up and unwitnessed onset strokes. The patterns of time of onset were analyzed: 1) hourly, 2) in 4-hour increments, and 3) daytime (08:00-19:59) vs. night-time (20:00-07:59). Diurnal variation in presenting demographic/clinical features were assessed using ANOVA, Kruskal-Wallis, t-tests, and Wilcoxon Rank-Sum. Results: Among 1615 patients (1202 enrolled on weekdays and 442 on weekends/holidays), 64% had IS, 12.5% TIA, and 23.5% IPH. ACI patients had different patterns of onset time (Figure). During weekdays, a broad plateau of highest rates of onset occurred 09:00-22:00. Conversely, during weekends/holidays, a unimodal peak was observed between 14:00-16:00. In contrast, patterns of onset time in IPH patients were broadly similar, with bimodal peaks on both weekdays and weekends/holidays. However, the first peak occurred earlier on weekdays (09:00-12:00 vs. 11:00-13:00), with the second peak occurring within 17:00-20:00 in both groups. Conclusion: Acute cerebral ischemia shows marked, and intraparenchymal hemorrhage minor, pattern differences in onset times on weekdays vs. weekends/holidays, likely related to variations in times of greater physical activity and stress. These findings can inform EMS resource allocation to stroke, aligned with weekday vs. weekend/holiday onset patterns.

Background: Circadian variations in stroke onset provide critical information for allocation of prehospital and hospital resources in clinical care and clinical trials. Studies of stroke circadian timing have had conflicting findings, and understanding would benefit from analysis confined to patients with defined onset in waking and clearly distinguished ischemic and hemorrhagic stroke subtypes. Methods: We analyzed all patients enrolled in the NIH FAST-MAG phase 3 trial of field-initiated neuroprotective agent in patients with hyperacute stroke within 2h of onset (last known well). Onset times were analyzed in 1h time blocks throughout the 24h day-night cycle. Patient demographic and clinical features, medical history, imaging characteristics, and stroke deficit severity were evaluated for association with onset times. Results: Among 1632 patients, final diagnoses were acute cerebral ischemia in 76.2% and intracranial hemorrhage in 23.7%. Hourly circadian variation in onset is shown in the Figure. Acute cerebral ischemia (ACI) had a unimodal distribution with peak onset at midday (12:00-12:59); intracerebral hemorrhage (ICH) a bimodal distribution with peaks at mid-morning (08:00-08:59) and early evening (18:00-18:59). Events were markedly reduced in early morning, with only 3.4% starting in the 25% of the day between 00:00-05:59. The proportion of events that were hemorrhagic was higher in the first 8h of the day (00:00-07:59) than the remaining 16h, 33.3% vs 22.5%, p=0.006. Both among ACI and ICH patients, vascular risk factors, presenting deficit severity, and initial brain imaging findings were fairly homogenous throughout all day-night time periods. Conclusion: There is marked, more than 10-fold, circadian variation in onset of acute cerebrovascular disease, and circadian variation in the ratio of ischemic to hemorrhagic neurovascular events. These findings can inform resource planning for regional systems of acute stroke care.