Unknown onset ischemic strokes in patients last-seen-well >4.5 h: differences between wake-up and daytime-unwitnessed strokes

Patients with unknown time of stroke onset (UOS) represent around one-third of ischemic stroke patients. These are patients with wake-up stroke (WUS) or daytime-unwitnessed stroke (DUS), often presenting outside the time-window for reperfusion therapy. UOS patients presenting between 4.5 and 12 h after time of last-seen-well were included. Clinical and imaging characteristics were compared between WUS and DUS patients. Good functional outcome was defined as a modified Rankin scale of ≤2 at follow-up. Sixty-one UOS patients were included: 42 WUS and 19 DUS patients. Stroke severity at presentation was mild to moderate with a median National Institutes of Health Stroke Scale of 5 in WUS and 6 in DUS patients. Time between last-seen-well and presentation at the hospital was shorter in patients with DUS compared to WUS (506 vs 362 min, p < 0.01). CT imaging results were similar, with a median Alberta Stroke Program Early CT Score of 10 for both WUS and DUS patients. After correction for age and NIHSS at presentation, no difference in good functional outcome was found between WUS (52%) and DUS (22%). In patients with unknown onset ischemic strokes presenting between 4.5 and 12 h after time of last-seen-well, clinical and radiological features were in large part similar between WUS and DUS. The outcome in the overall cohort was rather poor despite a favorable neuroimaging profile at presentation. These findings underscore the need for clinical trials in patients in whom stroke onset time is unknown.