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Introduction: It is uncertain whether lowered head position improves penumbral perfusion in ischemic stroke. Although a transcranial Doppler trial in large vessel occlusion (LVO) patients suggested improvement, a large pragmatic clinical trial in mixed stroke patients was neutral. We tested the tolerability and effect on penumbral perfusion of 20-degree head-down (Trendelenburg) positioning in patients with acute LVO stroke using automated quantitative CT perfusion (CTP). Methods: We enrolled LVO patients aged ≥60, 0-24h after onset, with ≥30mL anterior circulation CTP lesion volume (delay time [DT]>3, MISTAR software). CTP was repeated after 5 minutes of 20-degree Trendelenburg positioning using a custom-designed foam wedge. Neurological status (National Institutes of Health Stroke Scale [NIHSS]) and blood pressure were recorded in routine (30 degree up) and Trendelenburg position. Trendelenburg positioning was maintained for 24h if perfusion lesion volume significantly decreased (≥5mL) and reperfusion treatment was suboptimal. Results: The target of 25 patients were enrolled (14 [56%] male, median age 76 (interquartile range [IQR]71-84), baseline modified Rankin scale score 0 [IQR0-0], median NIHSS 20 [IQR 13-24]). Most patients (15/25 [60%]) had an acute M1 middle cerebral artery (MCA) occlusion, 6 (24%) an occluded M2 MCA and 4 (16%) an occluded ICA. Stroke etiology was predominantly (15/25 [60%]) cardioembolic.Median (IQR) DT>3seconds lesion volume was significantly reduced by Trendelenburg compared with conventional horizontal CT positioning (114mL [94-204] vs 149mL [76-153] p=0.0027)). This was not explained by changes in blood pressure, which was unaltered (mean 148mmHg (+/- standard deviation 29) vs 143 (+/-27); p=0.129). Head position did not alter clinical severity (NIHSS 13 [IQR 9-28]) in both positions). A significant lesion volume reduction with Trendelenburg positioning was seen in 15/25 patients (60%); 7 received continued Trendelenburg positioning due to incomplete reperfusion. Head down positioning was well tolerated in the majority (4/7 [57%]), without serious adverse events. Conclusion: Head-down (Trendelenburg) positioning improves penumbral perfusion in acute LVO ischemic stroke and is well-tolerated.

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