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CIRCADIAN TIME OF ISCHEMIC STROKE ONSET AFFECTS PRESENTING SEVERITY, ACUTE PROGRESSION, AND LONG-TERM OUTCOME
Abstract
Background and Aims
Preclinical data suggest circadian variation in ischemic stroke progression, with more active cell death and infarct growth in rodent models with inactive phase (daytime) than active phase (nighttime) stroke onset. We aimed to examine the association of stroke onset time with presenting severity, early neurological deterioration (END), and long-term functional outcome in human ischemic stroke.
Methods
This nationwide multi-center study included 17,461 consecutive patients with witnessed ischemic stroke within 6 hours of onset. We assessed circadian effects on initial stroke severity (National Institutes of Health Stroke Scale [NIHSS] score at admission), END, and favorable functional outcome (3-month modified Rankin Scale [mRS] score 0-2 versus 3-6).
Results
Mean age was 66.9 (SD 13.4) years, and 6,900 (39.5%) were women. When stroke onset times were grouped by 4-hour intervals, a monotonic gradient in presenting NIHSS score was noted, rising from a nadir in 06:00 to 10:00 to a peak in 02:00 to 06:00. The 18:00 to 22:00 and 22:00 to 02:00 onset stroke patients were more likely to experience END than the 06:00 to 10:00 onset stroke patients. At 3 months, there was a monotonic gradient in the rate of favorable functional outcome, falling from a peak at 06:00 to 10:00 to a nadir at 22:00 to 02:00.
Conclusions
Night-onset stroke, compared with day-onset stroke, is associated with higher presenting neurologic severity, more frequent END, and worse 3-month functional outcome. Therefore, circadian time of onset is an important additional variable for inclusion in epidemiologic natural history studies and in therapeutic trials for acute ischemic stroke.