James Michael L, Blessing Robert, Bennett Ellen, Laskowitz Daniel T
Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
J Stroke Cerebrovasc Dis. 2009 Mar-Apr;18(2):144-9. doi: 10.1016/j.jstrokecerebrovasdis.2008.09.012.
To address the mechanisms by which apoE polymorphism affects functional outcome after intracerebral hemorrhage in humans, we tested the hypothesis that the presence of the APOE4 allele results in amplified inflammatory responses and increased cerebral edema.
We prospectively enrolled and collected data on 21 adult patients consecutively admitted to Duke University Hospital with supratentorial intracerebral hematoma including hemorrhage volume, midline shift, modified Rankin Score, Glasgow Outcome Score, and APOE genotype. Hemorrhage size (cm(3)) and midline shift (mm), at the level of the thalamus, were measured by computed tomography within 36 hours of admission. Rankin and Glasgow Scores were determined at discharge. Student's t-test was used to analyze hemorrhage size, midline shift, and Glasgow Outcome Score and logistical regression were used to measure allele affect on modified Rankin Score. When analyzing modified Rankin Score, patients were grouped by favorable outcome (0-2) or unfavorable (3-6).
Out of 21 patients, 11 possessed at least 1 APOE4 allele (APOE4+). There was no difference in hemorrhage volume (25.8 v 38.3 mm for APOE4- v APOE4+, respectively) between the groups, but there was a significant difference in midline shift (P = .04, 0.7 v 4 mm). Functional outcomes were worse for the patients possessing at least 1 APOE4 allele (P = .04)
The presence of APOE4 is associated with poor functional outcomes in humans after intracerebral hemorrhage. Our data suggest that the mechanism for this may be increased cerebral edema and not larger hematoma volume.
为了探究载脂蛋白E(apoE)基因多态性影响人类脑出血后功能转归的机制,我们检验了如下假设:APOE4等位基因的存在会导致炎症反应增强和脑水肿加重。
我们前瞻性地纳入并收集了21例连续入住杜克大学医院的幕上脑出血成年患者的数据,包括出血量、中线移位、改良Rankin评分、格拉斯哥预后评分和APOE基因型。入院36小时内通过计算机断层扫描测量丘脑水平的出血大小(立方厘米)和中线移位(毫米)。出院时确定Rankin评分和格拉斯哥评分。采用学生t检验分析出血大小、中线移位和格拉斯哥预后评分,并采用逻辑回归分析等位基因对改良Rankin评分的影响。在分析改良Rankin评分时,将患者按良好预后(0 - 2分)或不良预后(3 - 6分)分组。
21例患者中,11例至少携带1个APOE4等位基因(APOE4+)。两组间出血量无差异(APOE4-组和APOE4+组分别为25.8立方厘米和38.3立方厘米),但中线移位有显著差异(P = 0.04,分别为0.7毫米和4毫米)。至少携带1个APOE4等位基因的患者功能转归较差(P = 0.04)。
APOE4的存在与人类脑出血后的不良功能转归相关。我们的数据表明,其机制可能是脑水肿加重而非血肿体积增大。