Melbourne Brain Centre, Royal Melbourne Hospital, University of Melbourne, Parkville, Australia (F.C.N., N.Y., G.S., S.M.D., B.C.V.C.).
Austin Health, Heidelberg, Australia (F.C.N.).
Stroke. 2022 Aug;53(8):2628-2636. doi: 10.1161/STROKEAHA.121.037073. Epub 2022 Apr 22.
Cerebral edema after large hemispheric infarction is associated with poor functional outcome and mortality. Net water uptake (NWU) quantifies the degree of hypoattenuation on unenhanced-computed tomography (CT) and is increasingly used to measure cerebral edema in stroke research. Hemorrhagic transformation and parenchymal contrast staining after thrombectomy may confound NWU measurements. We investigated the correlation of NWU measured postthrombectomy with volumetric markers of cerebral edema and association with functional outcomes.
In a pooled individual patient level analysis of patients presenting with anterior circulation large hemispheric infarction (core 80-300 mL or Alberta Stroke Program Early CT Score ≤5) in the HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke trials) data set, cerebral edema was defined as the volumetric expansion of the ischemic hemisphere expressed as a ratio to the contralateral hemisphere(rHV). NWU and midline-shift were compared with rHV as the reference standard on 24-hour follow-up CT, adjusted for hemorrhagic transformation and the use of thrombectomy. Association between edema markers and day 90 functional outcomes (modified Rankin Scale) was assessed using ordinal logistic regression.
Overall (n=144), there was no correlation between NWU and rHV (r=0.055, =0.51). In sub-group analyses, a weak correlation between NWU with rHV was observed after excluding patients with any degree of hemorrhagic transformation (r=0.211, =0.015), which further improved after excluding thrombectomy patients (r=0.453, =0.001). Midline-shift correlated strongly with rHV in all sub-group analyses (r>0.753, =0.001). Functional outcome at 90 days was negatively associated with rHV (adjusted common odds ratio, 0.46 [95% CI, 0.32-0.65]; <0.001) and midline-shift (adjusted common odds ratio, 0.85 [95% CI, 0.78-0.92]; <0.001) but not NWU (adjusted common odds ratio, 1.00 [95% CI, 0.97-1.03]; =0.84), adjusted for age, baseline National Institutes of Health Stroke Scale, and thrombectomy. Prognostic performance of NWU improved after excluding patients with hemorrhagic transformation and thrombectomy (adjusted odds ratio, 0.90 [95% CI, 0.80-1.02]; =0.10).
NWU correlated poorly with conventional markers of cerebral edema and was not associated with clinical outcome in the presence of hemorrhagic transformation and thrombectomy. Measuring NWU postthrombectomy requires validation before implementation into clinical research. At present, the use of NWU should be limited to baseline CT, or follow-up CT only in patients without hemorrhagic transformation or treatment with thrombectomy.
大脑半球大面积梗死后脑水肿与不良功能预后和死亡率相关。净水分摄取量（NWU）量化了 CT 平扫时的低衰减程度，越来越多地用于评估中风研究中的脑水肿。血栓切除术后的出血转化和实质对比染色可能会干扰 NWU 的测量。我们研究了血栓切除术后测量的 NWU 与脑水肿的容积标志物之间的相关性，以及与功能结局的关系。
在 HERMES（多血管内中风试验中高效再灌注评估）数据集内，对前循环大脑半球大面积梗死（核心体积 80-300ml 或 Alberta 中风计划早期 CT 评分≤5）患者进行个体患者水平的汇总分析，将脑水肿定义为缺血半球的容积扩张，用同侧半球的比值（rHV）表示。将 NWU 和中线移位与 24 小时随访 CT 上的 rHV 进行比较，对出血转化和血栓切除术的使用进行了调整。使用有序逻辑回归评估水肿标志物与第 90 天功能结局（改良 Rankin 量表）之间的关系。
总体（n=144）中，NWU 与 rHV 之间无相关性（r=0.055，=0.51）。在亚组分析中，在排除任何程度出血转化的患者后，NWU 与 rHV 之间存在较弱的相关性（r=0.211，=0.015），在排除血栓切除术患者后，相关性进一步改善（r=0.453，=0.001）。中线移位在所有亚组分析中与 rHV 高度相关（r>0.753，=0.001）。90 天时的功能结局与 rHV 呈负相关（调整后的共同优势比，0.46[95%可信区间，0.32-0.65]；<0.001）和中线移位（调整后的共同优势比，0.85[95%可信区间，0.78-0.92]；<0.001），但与 NWU 无关（调整后的共同优势比，1.00[95%可信区间，0.97-1.03]；=0.84），调整因素为年龄、基线国立卫生研究院中风量表和血栓切除术。在排除出血转化和血栓切除术患者后，NWU 的预后性能有所改善（调整后的优势比，0.90[95%可信区间，0.80-1.02]；=0.10）。
NWU 与脑水肿的常规标志物相关性差，且在存在出血转化和血栓切除术的情况下与临床结局无关。在实施到临床研究之前，需要对血栓切除术后的 NWU 测量进行验证。目前，NWU 的使用应仅限于基线 CT 或无出血转化或接受血栓切除术治疗的患者的随访 CT。
