Landreneau Margaret J, Mullen Michael T, Messé Steven R, Cucchiara Brett, Sheth Kevin N, McCullough Louise D, Kasner Scott E, Sansing Lauren H
Department of Neurology Yale University School of Medicine New Haven Connecticut.
Department of Neurology Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania.
Ann Clin Transl Neurol. 2018 Jul 3;5(8):962-970. doi: 10.1002/acn3.595. eCollection 2018 Aug.
Intracerebral hemorrhage carries a high mortality and survivors are frequently left with significant disability. Immunological mechanisms may play an important role in hemorrhage-induced brain injury, however, research linking these mechanisms with clinical outcome remains limited. We aim to identify serum inflammatory mediators that are associated with outcome after intracerebral hemorrhage in order to translate data from experimental models to a patient cohort and identify potential targets worthy of reverse translation.
A prospective cohort study at two comprehensive stroke centers enrolled patients with spontaneous intracerebral hemorrhage. Peripheral blood was collected at 6, 24, and 72 h from onset. Functional outcome was assessed at 90 days using the modified Rankin Scale (mRS). Serum inflammatory mediators were measured using multiplex ELISA. Multivariable modeling identified serum biomarkers independently associated with functional outcome at 90 days.
115 patients completed the study. At 6 h after onset, patients with elevated CCL2 had worse mRS score at day 90 (OR 4.07, 95% CI 1.27-13.10, = 0.02) after adjusting for age, gender, ICH volume, IVH, infratentorial location and NIHSS score. At 24 and 72 h after onset, elevation in CXCL10 was independently associated with worse 90 days mRS score (24 h: OR 8.08, 95% CI 2.69-24.30, < 0.001; 72 h: OR 3.89, 95% CI 1.12-13.49, = 0.03).
Acute and subacute elevations in specific immune factors are associated with poor outcome, highlighting potential pathways that may contribute to ongoing brain injury in patients with intracerebral hemorrhage.
脑出血死亡率高，幸存者常伴有严重残疾。免疫机制可能在出血性脑损伤中起重要作用，然而，将这些机制与临床结局联系起来的研究仍然有限。我们旨在确定与脑出血后结局相关的血清炎症介质，以便将实验模型的数据转化为患者队列，并确定值得反向转化的潜在靶点。
在两个综合卒中中心进行的一项前瞻性队列研究纳入了自发性脑出血患者。发病后6、24和72小时采集外周血。使用改良Rankin量表（mRS）在90天时评估功能结局。使用多重ELISA测量血清炎症介质。多变量模型确定了与90天时功能结局独立相关的血清生物标志物。
115名患者完成了研究。发病后6小时，在校正年龄、性别、脑出血体积、脑室内出血、幕下位置和美国国立卫生研究院卒中量表（NIHSS）评分后，CCL2升高的患者在第90天的mRS评分更差（OR 4.07，95%CI 1.27-13.10，P = 0.02）。发病后24和72小时，CXCL10升高与90天mRS评分更差独立相关（24小时：OR 8.08，95%CI 2.69-24.30，P < 0.001；72小时：OR 3.89，95%CI 1.12-13.49，P = 0.03）。
特定免疫因子的急性和亚急性升高与不良结局相关，突出了可能导致脑出血患者持续脑损伤的潜在途径。
