What is the prevalence of wake-up strokes and strokes of unknown onset?

Prevalence of Wake-Up Strokes and Strokes of Unknown Onset

Wake-up strokes account for approximately 25% of all ischemic strokes, while strokes of unknown onset collectively represent about one-third of the total stroke population. 1, 2, 3

Wake-Up Strokes

• Wake-up strokes (WUS) are defined as strokes that are first noticed upon awakening, when the exact time of symptom onset is unknown 3
• They represent approximately 20-25% of all ischemic stroke cases 1, 3
• This high prevalence is likely related to the circadian morning predominance of stroke occurrence 4
• The chronobiological pattern shows higher frequency in the first morning hours, associated with circadian fluctuations in blood pressure, heart rate, hemostatic processes, and atrial fibrillation episodes 3

Strokes of Unknown Onset

• Strokes of unknown onset (UOS) collectively represent approximately one-third of all ischemic stroke patients 2
• This category includes both wake-up strokes (WUS) and daytime-unwitnessed strokes (DUS) 2
• Daytime-unwitnessed strokes occur during waking hours but without witnesses to determine the exact onset time 2
• Time between last-seen-well and hospital presentation is typically shorter in DUS patients compared to WUS patients (362 vs 506 minutes in one study) 2

Clinical and Imaging Characteristics

• Stroke severity at presentation is often mild to moderate in both WUS and DUS patients 2
• CT imaging results are frequently similar between WUS and DUS patients 2
• There is considerable prevalence of CT perfusion mismatch and intracranial artery occlusions in patients with wake-up strokes, suggesting salvageable brain tissue 1
• Clinical and radiological features are largely similar between WUS and DUS patients presenting between 4.5 and 12 hours after time of last-seen-well 2

Treatment Implications

• Traditionally, patients with unknown stroke onset time were excluded from thrombolytic therapy due to uncertain time windows 3
• The WAKE-UP trial demonstrated the utility of MRI diffusion and fluid-attenuated inversion recovery (FLAIR) mismatch to identify patients eligible for thrombolysis when onset time is unknown 5
• Using this criterion could potentially increase the overall treatment rate with intravenous thrombolytics by 9% 5
• Perfusion-based imaging has identified patients with thrombolysis treatment potential up to 9 hours from symptom onset 5
• These imaging/tissue-based strategies provide opportunities for patients with unknown onset time, including those awakening from anesthesia with focal deficits 5

Clinical Approach to Unknown Onset Strokes

• For patients unable to provide onset time information or who awaken with stroke symptoms, the time of onset is defined as when the patient was last known to be "normal" 5
• Creative questioning to establish time anchors may allow treatment of patients initially identified as "onset time unknown" 5
• These include inquiring about pre-stroke or post-stroke cellular phone use (identifying call time stamps) or using television programming times 5
• Patients with "wake-up" strokes may identify a time point when they were ambulatory to the bathroom or kitchen 5

Emerging Treatment Approaches

• Recent clinical trials are enrolling wake-up stroke patients based on imaging findings, using either DWI-FLAIR mismatch or penumbral imaging 6
• There is a shift from rigid time-frame based therapy to a tissue-based individualized treatment approach 4
• Advanced imaging techniques are increasingly used to identify salvageable brain tissue regardless of known onset time 1, 6