Supplementary Material for: Predictors of early versus delayed neurological deterioration after thrombolysis for ischemic stroke: ENCHANTED study

Background and Purpose: We aimed to determine predictors of early (END) and delayed neurological deterioration (DND) and their association with functional outcome in patients with acute ischemic stroke (AIS) who participated in the international Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED).
Methods: END and DND were defined as scores of a ≥2 point increase on the National Institutes of Health Stroke Scale (NIHSS) or ≥1 point decrease on Glasgow coma scale, or death, from baseline to 24 hours and 24 hours to 72 hours, respectively. Multivariable logistic regression models were used to determine independent predictors of END and DND and their association with 90-day outcomes (dichotomous scores on the modified Rankin scale [mRS] of 2-6 vs 0-1 and 3-6 vs 0-2, and death).
Results: Of 4496 patients, 871 (19.4%) and 302 (8.4%) patients experienced END and DND, respectively. Higher baseline NIHSS score, older age, large artery occlusion due to significant atheroma, cardioembolic stroke subtype, hemorrhagic infarction and parenchymatous hematoma within 24 hours, were all independent predictors for both END (all P ≤0.01) and DND (all P ≤0.024). Moreover, higher baseline systolic blood pressure (BP) (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.02-1.12), higher diastolic BP variability within 24 hours (OR 1.07, 95% CI 1.04-1.09), patients from Asia (OR 1.25, 95% CI 1.03-1.52) were the only independent predictors for END. However, Asian ethnicity was negatively associated with DND (OR 0.64, 95% CI 0.47-0.86). Hemorrhagic infarction and parenchymatous hematoma within 24 hours were the key predictor of END across all stroke subtypes. END and DND were all associated with a poor functional outcome at 90 days (all P<0.001).
Conclusions: We identified overlapping and unique demographic and clinical predictors of END and DND after thrombolysis for acute ischemic stroke. Both END and DND predict unfavorable outcomes at 90 days.

研究背景与目的：本研究旨在明确参与国际强化血压控制与溶栓卒中研究（Enhanced Control of Hypertension and Thrombolysis Stroke Study, ENCHANTED）的急性缺血性卒中（acute ischemic stroke, AIS）患者的早期神经功能恶化（early neurological deterioration, END）与迟发性神经功能恶化（delayed neurological deterioration, DND）的预测因素，及其与患者功能预后的关联。
研究方法：本研究分别将基线至24小时内、24小时至72小时内，美国国立卫生研究院卒中量表（National Institutes of Health Stroke Scale, NIHSS）评分升高≥2分或格拉斯哥昏迷量表（Glasgow Coma Scale）评分降低≥1分，或死亡，定义为END与DND。采用多变量logistic回归模型，分析END与DND的独立预测因素，及其与90天预后的关联：改良Rankin量表（modified Rankin Scale, mRS）评分二分法为2~6分 vs 0~1分、3~6分 vs 0~2分，以及死亡结局。
研究结果：共纳入4496例患者，其中871例（19.4%）与302例（8.4%）分别发生END与DND。较高的基线NIHSS评分、高龄、严重动脉粥样硬化所致大动脉闭塞、心源性卒中亚型、24小时内出现出血性梗死及脑实质血肿，均为END（所有P≤0.01）与DND（所有P≤0.024）的共同独立预测因素。此外，较高的基线收缩压[比值比（odds ratio, OR）=1.07，95%置信区间（confidence interval, CI）：1.02~1.12]、24小时内舒张压变异性升高（OR=1.07，95%CI：1.04~1.09）、亚洲籍患者（OR=1.25，95%CI：1.03~1.52）为END仅有的独立预测因素。然而，亚洲裔与DND呈负相关（OR=0.64，95%CI：0.47~0.86）。24小时内出现的出血性梗死与脑实质血肿是所有卒中亚型中END的关键预测因素。END与DND均与90天不良功能预后显著相关（所有P<0.001）。
研究结论：本研究明确了急性缺血性卒中溶栓治疗后END与DND的重叠及独特的人口学与临床预测因素。END与DND均可预测患者90天的不良功能预后。