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The dawn of unknown‐onset strokes

We read with interest the article by Escalard et al. [1]; it aimed to evaluate the results of thrombectomy for unknownonset strokes (UOS) treated after a diffusion weighted imaging/fluid attenuated inversion recovery (DWI-FLAIR) mismatch based selection compared with known-onset strokes (KOS). They found that thrombectomy of UOS with anterior circulation occlusion and DWI-FLAIR mismatch appears to be as safe and efficient as thrombectomy of KOS within 6 h from onset. If this conclusion can be confirmed as safe and efficient in the ongoing randomized trials, it will result in more UOS patients, who have been excluded from thrombolytic therapy before, being treated effectively. However, we note that patients who had an acute ischaemic stroke with an unknown time of symptom onset in this study included wake-up strokes (WUS) and day-time unwitnessed strokes (DUS), and there was no subgroup analysis between these two different groups. The available evidence showed that ischaemic stroke subtypes were different between WUS and DUS. Cardioembolism was more frequent in DUS patients, whereas small vessel occlusive disease was more frequently observed in WUS patients [2]. Meanwhile, other research has shown that haemodynamic changes in cerebral blood flow during sleep contribute to the pathogenesis of WUS; lower arterial pressure during sleep with concomitant vascular stenosis may play an important role in the manifestation of stroke [3]. This might indicate that DUS could benefit more from thrombectomy treatment. Cardioembolic stroke usually causes a sudden onset of neurological deficit and large infarction, and presents severe stroke symptoms [4], so DUS patients always present with more severe neurological deficit and arrive at the hospital earlier after symptom onset recognition compared to WUS patients, and this may result in DUS patients being more likely to receive treatment. Due to the different characteristics and pathophysiology mentioned above between DUS and WUS, subgroup analysis in this study may be important in deciding which group could result in greater benefit from thrombectomy. The study by Escalard et al. [1] suggests that DWI-FLAIR mismatch for patient selection rather than time from onset can be safely and efficiently applied to select eligible patients when the time of onset is unknown. But it remains unclear which, DUS or WUS patients, could benefit more from this treatment pattern. Further work is warranted to validate its effectiveness and security.