Treatment Concepts for Wake-Up Stroke and Stroke With Unknown Time of Symptom Onset.

Abstract

Patients waking up with stroke symptoms represent a distinct but underprivileged subgroup of patients with stroke. Because in wake-up stroke the time of symptom onset is unknown these patients are a challenge to acute stroke treatment. On the basis of licensing criteria and international guideline recommendations, the unknown time window since symptom onset excludes the majority of patients with wake-up stroke from reperfusion treatment with intravenous thrombolysis.1,2 The same applies for endovascular reperfusion treatment that recently was demonstrated to be effective in 5 randomized controlled trials (RCTs).3–7 In 3 of these trials, treatment was restricted to a time window of <6 hours onset, and in the others the vast majority of patients was also treated within 6 hours of symptom onset. Thus, the time point when a patient with wake-up stroke was last seen well usually also lies beyond the time window within which endovascular stroke treatment was demonstrated to be safe and effective. However, a relevant number of these patients might benefit from reperfusion treatment. In this review, we will give an overview on brain imaging concepts suggested to guide reperfusion treatment in patients with unknown time of symptom onset. We will summarize available information on reperfusion treatment and provide an update on ongoing clinical trials of intravenous thrombolysis and endovascular treatment in these patients. Wake-up stroke is a frequent condition, affecting ≈20% of patients with stroke.8–11 Adding cases with unknown time of symptom onset for other reasons, for example, nonwitnessed stroke with aphasia or disturbance of consciousness, to these numbers, in ≤30% of patients with acute stroke time of symptom onset is unknown.8–11 Imaging studies suggest that stroke onset may have occurred only shortly before waking up in a large proportion of these patients, as frequency …