Du Yili, Mallinger Leigh Ann, Reinert Allyson L, Chatzidakis Stefanos, Ibrahim Nawal J, Wirth Gabriella, Kumar Atul, Avula Amrit, Cheng Huimin, Greer David M, Dhar Rajat, Ong Charlene
Boston University School of Public Health.
BMC: Boston Medical Center.
Res Sq. 2025 Sep 17:rs.3.rs-7207393. doi: 10.21203/rs.3.rs-7207393/v1.
Cerebral edema is a life-threatening complication of large ischemic stroke. Imaging assessment of global and hemispheric cerebrospinal fluid (CSF) volumetrics quantifies edema progression, while quantitative pupillometry provides real-time bedside assessment of neurologic decline. However, the relationship between the two and their combined value for predicting neurologic deterioration remains unclear.
We conducted a retrospective study of patients with large middle cerebral artery strokes admitted to Boston Medical Center between 2019 and 2024. Eligible patients had ≥1 head CT and ≥3 pupillometry measurements. Total and hemispheric CSF volumes were extracted using an automated image analysis pipeline. Average pupillometry variables, including the Neurological Pupil index (NPi) and dilation velocity, were aligned to imaging within ±1 hour and within the subsequent 24-hours of each image. Associations between pupillometry and CSF volumetrics were evaluated using Spearman's correlations and linear mixed-effects models adjusted for age, sex, and standardized baseline brain volume. Cox proportional hazards models with time-dependent covariates were used to assess the predictive value of CSF and pupillometry markers for time-to-neurologic deterioration. We compared model performance using likelihood ratio tests and time-dependent area under the curve (AUC) metrics.
Seventy-one patients (mean age 66 ±16 years; 59% women) with 249 CT images were included. Pupillometry and CSF measures were significantly correlated in the first 48-hours post-stroke. In adjusted models, lower hemispheric CSF volume ratio was associated with lower NPi (β=1.55, p=0.02) and greater NPi difference (β=-1.53, p<0.01). Thirty-two (46%) of 69 eligible patients experienced neurologic deterioration. Models including CSF volume and pupillometry outperformed those with pupillometry only (AUC 83.5% v. 81.0%; χ=4.63, =0.03).
Pupillometry and imaging-derived CSF volumetrics are temporally aligned biomarkers that improve prediction of neurologic deterioration, supporting their complementary roles in monitoring cerebral edema.
脑水肿是大面积缺血性中风的一种危及生命的并发症。对全脑和半球脑脊液（CSF）容量的影像学评估可量化水肿进展，而定量瞳孔测量可在床边实时评估神经功能衰退。然而，两者之间的关系及其对预测神经功能恶化的综合价值仍不明确。
我们对2019年至2024年间入住波士顿医疗中心的大脑中动脉大面积中风患者进行了一项回顾性研究。符合条件的患者有≥1次头部CT和≥3次瞳孔测量。使用自动化图像分析流程提取全脑和半球CSF容量。平均瞳孔测量变量，包括神经瞳孔指数（NPi）和扩张速度，在每次图像的±1小时内以及随后的24小时内与影像学数据进行匹配。使用Spearman相关性分析和调整了年龄、性别和标准化基线脑容量的线性混合效应模型评估瞳孔测量与CSF容量之间的关联。使用具有时间依赖性协变量的Cox比例风险模型评估CSF和瞳孔测量标志物对神经功能恶化时间的预测价值。我们使用似然比检验和时间依赖性曲线下面积（AUC）指标比较模型性能。
纳入了71例患者（平均年龄66±16岁；59%为女性），共249张CT图像。中风后48小时内，瞳孔测量与CSF测量显著相关。在调整模型中，较低的半球CSF体积比与较低的NPi（β=1.55，p=0.02）和较大的NPi差异（β=-1.53，p<0.01）相关。69例符合条件的患者中有32例（46%）出现神经功能恶化。包括CSF容量和瞳孔测量的模型优于仅使用瞳孔测量的模型（AUC 83.5%对81.0%；χ=4.63，p=0.03）。
瞳孔测量和影像学衍生的CSF容量是时间上匹配的生物标志物，可改善对神经功能恶化的预测，支持它们在监测脑水肿中的互补作用。
