Bernstein Jacob E, Browne Jonathan D, Savla Paras, Wiginton James, Patchana Tye, Miulli Dan E, Wacker Margaret Rose, Duong Jason
Neurosurgery, Riverside University Health System Medical Center, Moreno Valley, USA.
School of Medicine, California University of Science and Medicine, Colton, USA.
Cureus. 2021 Jan 10;13(1):e12605. doi: 10.7759/cureus.12605.
Introduction Spontaneous intracerebral hemorrhage (ICH) results in significant morbidity and mortality. The pathogenesis of brain injury after ICH is thought to be due to mechanical damage followed by ischemic, cytotoxic, and inflammatory changes in the underlying and surrounding tissue. Various inflammatory and non-inflammatory biomarkers have been studied as predictors and potential therapeutic targets for intracerebral hemorrhage. Our prior study showed an association with low vascular endothelial growth factor (VEGF) levels and increased mortality. This current study looks to expand on our prior results and will look at the relationship between tumor necrosis factor alpha (TNFα), C-reactive protein (CRP), VEGF, Homocysteine (Hcy), and CRP to albumin ratio (CAR) in predicting outcomes and severity in spontaneous intracerebral hemorrhage. Methods We conducted a retrospective chart review of patients with spontaneous intracerebral hemorrhage with TNFα, CRP, VEGF, Hcy levels drawn on admission. Albumin and CRP levels on admission were used to calculate CAR. Ninety-nine patients were included in the study. Primary outcomes included death, early neurologic decline (END), and hemorrhage size. Secondary outcomes included late neurologic decline (LND), Glasgow Coma Scale (GCS) on admission, GCS on discharge, ICH score, change in hemorrhage size, need for surgical intervention, and length of ICU stay. Results A total of 99 patients were included in this study, with 42% requiring surgical intervention and an overall mortality of 16%. Basal ganglia hemorrhage was seen in 41% of patients. Hcy and CAR were significantly correlated with ICH size in basal ganglia patients (r-=0.36, p=0.03; r=0.43, p=0.03, respectively). CAR was significantly correlated with ICH score (r=0.33, p=0.007874). Admission VEGF levels less than 45 pg/ml had 8.4-fold increase in mortality (odds ratio [OR] 8.4545, p=0.0488). Patients with TNFα levels greater than 1.40 pg/ml had a 4.1-fold increase in mortality (OR 4.1, p=0.04) Conclusion Our study demonstrated that low levels (<45 pg/ml) of VEGF were associated with an 8.4-fold increase in mortality, supporting the neuroprotective effect of this protein. Elevated Hcy and CAR levels were associated with an increase in hemorrhage size in patients with basal ganglia hemorrhages. TNFα levels greater than 1.40 pg/ml were associated with a 4.1-fold increase in mortality, and this together with CAR being correlated with increased hemorrhage size and ICH score further demonstrate the inflammatory consequences after intracerebral hemorrhage. Future studies directed at lowering CRP, TNFα, and Hcy and/or increasing VEGF in intracerebral hemorrhage patients are needed and may be beneficial.
引言 自发性脑出血（ICH）会导致显著的发病率和死亡率。脑出血后脑损伤的发病机制被认为是由于机械损伤，随后在其下方及周围组织发生缺血、细胞毒性和炎症变化。各种炎症和非炎症生物标志物已被研究作为脑出血的预测指标和潜在治疗靶点。我们之前的研究表明低血管内皮生长因子（VEGF）水平与死亡率增加有关。本研究旨在扩展我们之前的结果，并将研究肿瘤坏死因子α（TNFα）、C反应蛋白（CRP）、VEGF、同型半胱氨酸（Hcy）以及CRP与白蛋白比值（CAR）之间的关系，以预测自发性脑出血的预后和严重程度。
方法 我们对入院时检测了TNFα、CRP、VEGF、Hcy水平的自发性脑出血患者进行了回顾性病历审查。入院时的白蛋白和CRP水平用于计算CAR。99名患者纳入研究。主要结局包括死亡、早期神经功能恶化（END）和出血大小。次要结局包括晚期神经功能恶化（LND）、入院时格拉斯哥昏迷量表（GCS）评分、出院时GCS评分、脑出血评分、出血大小变化、手术干预需求以及重症监护病房（ICU）住院时间。
结果 本研究共纳入99名患者，42%的患者需要手术干预，总体死亡率为16%。41%的患者出现基底节区出血。在基底节区出血患者中，Hcy和CAR与脑出血大小显著相关（分别为r = 0.36，p = 0.03；r = 0.43，p = 0.03）。CAR与脑出血评分显著相关（r = 0.33，p = 0.007874）。入院时VEGF水平低于45 pg/ml的患者死亡率增加8.4倍（比值比[OR] 8.4545，p = 0.0488）。TNFα水平大于1.40 pg/ml的患者死亡率增加4.1倍（OR 4.1，p = 0.04）
结论 我们的研究表明，低水平（<45 pg/ml）的VEGF与死亡率增加8.4倍有关，支持了该蛋白的神经保护作用。Hcy和CAR水平升高与基底节区出血患者的出血大小增加有关。TNFα水平大于1.40 pg/ml与死亡率增加4.1倍有关，这与CAR与出血大小增加和脑出血评分相关，进一步证明了脑出血后的炎症后果。未来需要针对降低脑出血患者的CRP、TNFα和Hcy水平和/或增加VEGF水平开展研究，这可能会带来益处。
