Abstract WP9: Ischemic Stroke Progression After Witnessed Onset in Daytime vs Night-Time

Abstract

Introduction: Early neurologic deterioration (END) and poor functional outcomes are more frequent with night than daytime onset of ischemic stroke. This variation may be related to: 1) circadian variation endogenous bodily rhythms and/or 2) extrinsic environmental time cues. Methods: To assess the contribution of extrinsic environmental time to ischemic stroke course, we evaluated patients with acute cerebral ischemia (ACI) onset within last 2h, enrolled in the NIH FAST-MAG trial of prehospital neuroprotection, consisting of patients with witnessed/wake onset. Results: Among 1235 ACI patients (ischemic stroke 1033, TIA 202), age was 70.8 [±13.2], 45.3% female, initial NIHSS 7 (IQR 2-15), LKW to randomization 59 mins (IQR 46-80), and 473 (38%) treated with IV lytics. Onset occurred during clock daytime (07:00-22:59) in 1147 (92.9%) and night-time (23:00-06:59) in 88 (7.1%). Patients were similar in 18 baseline characteristics, but night-onset had higher initial SBP (162 vs 155, p=0.01) and longer onset to paramedic times (33m vs 23m, p = 0.0002). Among non-lytic patients, both unadjusted and adjusted clinical outcomes were similar in night vs daytime patients, including END (13.6% vs 16.4%), 90d mRS 0-2 (63.6% vs 58.5%), and 90d mortality (10.2% vs 12.8%). Among lytic patients, clinical outcomes were also similar in night vs daytime onset patients, including unadjusted END (36% vs 21.7%), 90d mRS 0-2 (52% vs 46.9%), and 90d mortality (12% vs 17.4%). Night vs daytime onset did not modify the effect of magnesium vs placebo on outcome among either non-thrombolytic or thrombolytic-treated patients (Figure). Conclusion: Among acute cerebral ischemia patients, efficacy, safety, and neuroprotective agent response outcomes were not modified by witnessed onset during active versus inactive phase clock times. These findings suggest biological wake-sleep state rather than chronologic clock time is the driver of known circadian rhythmicity in stroke course.