Wake-up or unclear-onset strokes: are they waking up to the world of thrombolysis therapy?

Wake-up or unclear-onset strokes occur in up to one-fourth of patients with ischemic stroke. Although stroke severity and clinical outcomes appear to be poorer in wake-up strokes than nonwake-up strokes, many patients with wake-up strokes do not receive thrombolytic therapy because stroke onset time cannot be determined. Recent studies have suggested, however, that the actual onset time of wake-up stroke is close to the wake-up time. Furthermore, advanced imaging technologies may enable us to identify patients with favorable risk-benefit profiles for thrombolysis. Indeed, empirical thrombolytic treatments have suggested safety and feasibility of such therapy in these patients. Based on these promising results and the development of multimodal imaging methods, prospective thrombolysis trials using predefined imaging criteria are currently under way to test the safety and efficacy of thrombolysis in patients with wake-up or unclear-onset strokes. The establishment of optimal acute treatment strategies in this important yet so far neglected group of patients is eagerly awaited.