From the Hospices Civils de Lyon (A.B.-S., L.M., C.D.B., T.-H.C., M.C., R.A., M.H., L.D., N.N., Y.B.); and Olea Medical (A.M., T.B.), La Ciotat, France.
Neurology. 2023 Aug 1;101(5):e502-e511. doi: 10.1212/WNL.0000000000207460. Epub 2023 Jun 8.
The aim of this study was to investigate the relationship between baseline blood-brain barrier (BBB) permeability and the kinetics of circulating inflammatory markers in a cohort of acute ischemic stroke (AIS) patients treated with mechanical thrombectomy.
The CoHort of Patients to Identify Biological and Imaging markerS of CardiovascUlar Outcomes in Stroke includes AIS patients treated with mechanical thrombectomy after admission MRI and undergoing a sequential assessment of circulating inflammatory markers. Baseline dynamic susceptibility perfusion MRI was postprocessed with arrival time correction to provide K2 maps reflecting BBB permeability. After coregistration of apparent diffusion coefficient and K2 maps, the 90th percentile of K2 value was extracted within baseline ischemic core and expressed as a percentage change compared with contralateral normal-appearing white matter. Population was dichotomized according to the median K2 value. Univariable and multiple variable logistic regression analyses were performed to investigate factors associated with increased pretreatment BBB permeability in the whole population and in patients with symptom onset <6 hours.
In the whole population (n = 105 patients, median K2 = 1.59), patients with an increased BBB permeability had higher serum levels of matrix metalloproteinase (MMP)-9 at H48 ( = 0.02), a higher C-reactive protein (CRP) serum level at H48 ( = 0.01), poorer collateral status ( = 0.01), and a larger baseline ischemic core ( < 0.001). They were more likely to have hemorrhagic transformation ( = 0.008), larger final lesion volume ( = 0.02), and worst neurologic outcome at 3 months ( = 0.04). The multiple variable logistic regression indicated that an increased BBB permeability was associated only with ischemic core volume (odds ratio [OR] 1.04, 95% CI 1.01-1.06, < 0.0001). Restricting analysis to patients with symptom onset <6 hours (n = 72, median K2 = 1.27), participants with an increased BBB permeability had higher serum levels of MMP-9 at H0 ( = 0.005), H6 ( = 0.004), H24 ( = 0.02), and H48 ( = 0.01), higher CRP levels at H48 ( = 0.02), and a larger baseline ischemic core ( < 0.0001). The multiple variable logistic analysis showed that increased BBB permeability was independently associated with higher H0 MMP-9 levels (OR 1.33, 95% CI 1.12-1.65, = 0.01) and a larger ischemic core (OR 1.27, 95% CI 1.08-1.59, = 0.04).
In AIS patients, increased BBB permeability is associated with a larger ischemic core. In the subgroup of patients with symptom onset <6 hours, increased BBB permeability is independently associated with higher H0 MMP-9 levels and a larger ischemic core.
本研究旨在探讨急性缺血性脑卒中（AIS）患者接受机械取栓治疗后，基线血脑屏障（BBB）通透性与循环炎症标志物动力学之间的关系。
该队列研究纳入了接受机械取栓治疗的 AIS 患者，这些患者在入院 MRI 后进行了连续的循环炎症标志物评估。采用到达时间校正对动态磁敏感对比灌注 MRI 进行后处理，以提供反映 BBB 通透性的 K2 图。在表观弥散系数和 K2 图的配准后，在基线缺血核心内提取 K2 值的第 90 百分位数，并表示为与对侧正常表现的白质相比的百分比变化。根据 K2 值的中位数将人群分为两组。对整个人群（n=105 例，K2中位数=1.59）和发病<6 小时的患者进行单变量和多变量逻辑回归分析，以探讨与预处理 BBB 通透性增加相关的因素。
在整个人群中，K2 增加的患者在 H48 时的基质金属蛋白酶（MMP）-9 血清水平更高（=0.02），H48 时 C 反应蛋白（CRP）血清水平更高（=0.01），侧支循环状态较差（=0.01），基线缺血核心更大（<0.001）。他们更有可能发生出血性转化（=0.008）、最终病变体积更大（=0.02）和 3 个月时神经功能预后更差（=0.04）。多变量逻辑回归表明，增加的 BBB 通透性仅与缺血核心体积相关（优势比[OR]1.04，95%置信区间[CI]1.01-1.06，<0.0001）。将分析限制在发病<6 小时的患者（n=72，K2中位数=1.27）中，K2 增加的患者在 H0（=0.005）、H6（=0.004）、H24（=0.02）和 H48（=0.01）时的 MMP-9 血清水平更高，在 H48 时 CRP 水平更高（=0.02），且基线缺血核心更大（<0.0001）。多变量逻辑分析表明，增加的 BBB 通透性与较高的 H0 MMP-9 水平（OR 1.33，95%CI 1.12-1.65，=0.01）和较大的缺血核心（OR 1.27，95%CI 1.08-1.59，=0.04）独立相关。
在 AIS 患者中，增加的 BBB 通透性与较大的缺血核心有关。在发病<6 小时的亚组患者中，增加的 BBB 通透性与较高的 H0 MMP-9 水平和较大的缺血核心独立相关。
