Department of Neurosciences and Mental Health (Neurology), Hospital de Santa Maria/CHULN, Universidade de Lisboa, Lisbon, Portugal.
Institute of Anatomy, Faculdade de Medicina, University of Lisbon, Lisbon, Portugal.
Thromb Haemost. 2021 Nov;121(11):1476-1482. doi: 10.1055/s-0041-1726094. Epub 2021 Mar 23.
Elucidating mechanisms of brain damage in cerebral venous thrombosis (CVT) would be instrumental to develop targeted therapies and improve prognosis prediction. Matrix metalloproteinase-9 (MMP-9), a gelatinase that degrades major components of the basal lamina, has been associated to blood-brain barrier disruption. We aimed to assess, in patients with CVT, the temporal change in serum concentrations of MMP-9 and its association with key imaging and clinical outcomes.
Pathophysiology of Venous Infarction-PRediction of InfarctiOn and RecanalIzaTion in CVT (PRIORITy-CVT) was a multicenter prospective cohort study of patients with newly diagnosed CVT. Serial collection of peripheral blood samples performed on day 1, 3, and 8, and standardized magnetic resonance imaging on day 1, 8, and 90. MMP-9 was quantified using enzyme-linked immunosorbent assay in 59 patients and 22 healthy controls. Primary outcomes were parenchymal brain lesion, early evolution of brain lesion, early recanalization, and functional outcome on day 90.
CVT patients with parenchymal brain lesion had higher baseline concentrations of MMP-9 compared with controls (adjusted = 0.001). The area under receiver operating characteristic curve value for MMP-9 for predicting brain lesion was 0.71 (95% confidence interval [CI]: 0.57-0.85, = 0.009). Patients with venous recanalization showed early decline of circulating MMP-9 and significantly lower levels on day 8 ( = 0.021). Higher MMP-9 on day 8 was associated with persistent venous occlusion (odds ratio: 1.20 [per 20 ng/mL], 95% CI: 1.02-1.43, = 0.030).
We report a novel relationship among MMP-9, parenchymal brain damage, and early venous recanalization, suggesting that circulating MMP-9 is a dynamic marker of brain tissue damage in patients with CVT.
阐明脑静脉血栓形成（CVT）中脑损伤的机制对于开发靶向治疗和改善预后预测至关重要。基质金属蛋白酶-9（MMP-9）是一种能够降解基底膜主要成分的明胶酶，与血脑屏障破坏有关。我们旨在评估 CVT 患者中 MMP-9 的血清浓度随时间的变化及其与关键影像学和临床结局的关系。
静脉梗死的病理生理学-预测 CVT 中的梗死和再通（PRIORITy-CVT）是一项多中心前瞻性队列研究，纳入了新诊断为 CVT 的患者。在第 1、3 和 8 天连续采集外周血样本，并在第 1、8 和 90 天进行标准化磁共振成像。在 59 例患者和 22 例健康对照者中使用酶联免疫吸附试验定量 MMP-9。主要结局是实质脑病变、脑病变早期演变、早期再通和 90 天的功能结局。
与对照组相比，有实质脑病变的 CVT 患者基线 MMP-9 浓度更高（调整后 = 0.001）。MMP-9 预测脑病变的受试者工作特征曲线下面积为 0.71（95%置信区间：0.57-0.85， = 0.009）。静脉再通的患者显示循环 MMP-9 早期下降，第 8 天的水平显著降低（ = 0.021）。第 8 天高 MMP-9 与持续性静脉闭塞相关（优势比：1.20 [每 20ng/mL]，95%置信区间：1.02-1.43， = 0.030）。
我们报告了 MMP-9、实质脑损伤和早期静脉再通之间的新关系，表明循环 MMP-9 是 CVT 患者脑组织损伤的动态标志物。
