Wake-up stroke and stroke of unknown onset: a critical review.

Patients, who wake up with an ischemic stroke, account for a large number of the total stroke population, due to circadian morning predominance of stroke. Currently, this subset of patients is excluded from revascularization-therapy since no exact time of onset is known. A large group of these patients might be eligible for therapy. In this review, we assessed the current literature about the hypothesis that wake-up-strokes occur just prior on awakening and if this subgroup differs in characteristics compared to the overall stroke population. We looked at the safety and efficacy of thrombolysis and interventional techniques in the group of patients with unknown stroke-onset. We performed a meta-analysis of the diagnostic accuracy of the diffusion-FLAIR mismatch in identifying stroke within 3 and 4.5 h. The different imaging-selection criteria that can be used to treat these patients are discussed. Additional research on imaging findings associated with recent stroke and penumbral imaging will eventually lead to a shift from a rigid time-frame based therapy to a tissue-based individualized treatment approach.