中性粒⁃淋巴细胞比值与脑白质疏松相关

目的：探讨脑白质疏松（leukoaraiosis,LA）的相关危险因素。方法：回顾性收集110例住院患者临床资料,所有患者均接受核磁共振检查,应用液体衰减恢复序列检查LA,根据Fazekas量表评估其严重程度,采用Logistic回归分析方法确定LA的危险因素。结果：110例患者中59例患者表现为无~轻度LA,51例表现为中~重度LA。多因素回归分析示年龄（OR=1.07,95%CI：1.02~1.12,P=0.003）、高血压（OR=2.51,95%CI：1.03~6.14,P=0.043）、中性粒?淋巴细胞比值（OR=1.34,95%CI：1.02~1.76,P=0.039）和中性粒细胞计数（P=0.010）与LA相关。结论：年龄、高血压、中性粒?淋巴细胞比值和中性粒细胞计数是LA的独立危险因素。     

Leukoaraiosis is associated with genes regulating blood–brain barrier homeostasis in ischaemic stroke patients

Background: The biologic agents causing leukoaraiosis are unknown. Our aim was to study the genetic basis of leukoaraiosis. Methods: We analyzed 212 single nucleotide polymorphisms (SNPs) in 142 patients with ischaemic stroke, generating a total of 30 104 genotypes. Seventy‐nine subjects (55.6%) presented leukoaraiosis measured by the Fazekas scale and 69 (48.6%) by ARWMC scale. We analyzed the presence of synergic associations between SNPs using the hfcc software. Finally, functional studies were performed in 56 subjects. The Ingenuity Pathways software (ipa ) was used to examine the role of the identified genes. Results: Six SNPs were associated with leukoaraiosis using both measuring scales. After logistic regression adjusted for leukoaraiosis risk factors, the rs2252070 of MMP13 (OR = 4.9, 95%CI: 1.34–17.9, P = 0.016), rs662 of PON1 (OR = 0.37, 95%CI: 0.15–0.87, P = 0.024) and rs1800779 of NOS3 (OR = 3.9, 95%CI: 1.38–11.38, P = 0.01) were independently associated with leukoaraiosis under a dominant/recessive model and the rs2290608 of IL5RA (OR = 0.46, 95%CI: 0.25–0.85, P = 0.013) and rs669 of A2M (OR = 2.5, 95%CI: 1.36–4.83, P = 0.004) under an additive model. Computational analysis showed a synergic association of rs10497212‐AA of ITGB6 and rs2290608‐GG of IL5RA with leukoaraiosis using both scales. (i) ARWMC (P = 1.3 × 10⁻⁴) and (ii) Fazekas (P = 4.5 × 10⁻⁵). Functional studies showed that the rs669 SNP was associated with plasma levels of A2M (P = 0.012) and A2M levels with leukoaraiosis in Fazekas scale (P = 0.02). ipa analysis revealed that the genes associated with leukoaraiosis were involved in blood–brain barrier (BBB) homeostasis. Conclusions: Amongst patients with ischaemic stroke, several genes associated with BBB homeostasis could be involved with a higher risk of leukoaraiosis.     

Reduced blood flow in normal white matter predicts development of leukoaraiosis

The purpose of this study was to investigate whether low cerebral blood flow (CBF) is associated with subsequent development of white matter hyperintensities (WMH). Patients were included from a longitudinal magnetic resonance (MR) imaging study of minor stroke/transient ischemic attack patients. Images were co-registered and new WMH at 18 months were identified by comparing follow-up imaging with baseline fluid-attenuated inversion recovery (FLAIR). Regions-of-interest (ROIs) were placed on FLAIR images in one of three categories: (1) WMH seen at both baseline and follow-up imaging, (2) new WMH seen only on follow-up imaging, and (3) regions of normal-appearing white matter at both time points. Registered CBF maps at baseline were used to measure CBF in the ROIs. A multivariable model was developed using mixed-effects logistic regression to determine the effect of baseline CBF on the development on new WMH. Forty patients were included. Mean age was 61±11 years, 30% were female. Low baseline CBF, female sex, and presence of diabetes were independently associated with the presence of new WMH on follow-up imaging. The odds of having new WMH on follow-up imaging reduces by 0.61 (95% confidence interval=0.57 to 0.65) for each 1 mL/100 g per minute increase in baseline CBF. We conclude that regions of white matter with low CBF develop new WMH on follow-up imaging.     

小鼠慢性脑血流低灌注状态的行为学检测及病理学观察

目的 观察小鼠慢性脑血流低灌注状态下行为学及其病理学变化.方法 62只C57BL/6小鼠均分为模型组和假手术组.模型组:采用内径为0.18 mm的微型弹簧圈套C57BL/6小鼠双侧颈总动脉,造成血管狭窄导致全脑血流低灌注状态;假手术组:仅暴露双侧颈总动脉,不圈套微型弹簧.在成模30 d时两组各取8只小鼠,采用八臂迷宫实验检测小鼠认知功能的改变,并在成模7、14 d和30 d时分别处死动物,采用Kluver-Barrera染色观察神经纤维改变及免疫组化观察胶质细胞增生程度,同时用Evans Blue荧光观察血脑屏障通透性的变化.结果 建模30 d后模型组八臂迷宫实验工作记忆错误显著多于假手术组(P<0.05).在成模7 d时未见显著病理变化,在14、30 d时观察到模型组脑白质区域神经纤维稀疏[胼胝体神经纤维损伤分级分别为(1.13±0.05)和(1.96±0.08),P<0.05],星形胶质细胞和小胶质细胞显著增生[胼胝体星型胶质细胞计数分别为(104.52±12.31)和(192.57±24.23),小胶质细胞计数分别为(98.25±15.27)和(172.36±18.29),P<0.01],Evans Blue荧光观察到脑内微血管血液成分外渗.结论 慢性脑血流低灌注状态导致小鼠的认知功能下降、胼胝体等白质神经纤维稀疏及胶质细胞增生.     

Cerebral leukoaraiosis in patients with stroke or TIA: clinical correlates and 1-year outcome

Background and purpose:  Cerebral leukoaraiosis is frequently observed in patients with acute stroke, but its clinical consequences on functional recovery remain incompletely defined. We evaluated the clinical correlates of leukoaraiosis, and its association with stroke-outcome in a cohort of consecutively hospitalized patients.
Methods:  One-thousand twenty-four consecutive patients with acute stroke or transient ischemic attack (TIA) undergoing brain CT were included in this single-center study. Patients were systematically evaluated at hospitalization and followed-up for 1 year. Mortality, functional outcome, quality of life (QoL), psychological distress, community integration, and patient perception of recovery were evaluated by leukoaraiosis severity. Adjusted ORs (95%CI) were calculated.
Results:  Moderate/severe leukoaraiosis was diagnosed in 177 patients (17.3%) and mild leukoaraiosis in 362 patients (35.3%). After 1 year, adjusted ORs for moderate/severe leukoaraiosis compared with no leukoaraiosis were 2.0 (95%CI 1.1–4.0) for Barthel Index ≤75; 1.9 (95%CI 0.9–4.0) for help needed in ADL; 2.5 (95%CI 1.0–6.3) for not feeling totally recovered; 2.0 (95%CI 1.1–4.1) for low QoL; 1.9 (95%CI 1.0–3.5) for psychological distress, and 1.6 (95%CI 0.9–2.9) for reduced community integration.
Conclusions:  In a large cohort of consecutive patients hospitalized for stroke or TIA, leukoaraiosis predicted poor functional recovery, worse QoL and community integration, and higher psychological distress during the first year following stroke onset.     

Cranial computed tomography associated with development of functional dependence in a community-based elderly population

OBJECTIVE: To investigate whether changes at computed tomography (CT) imaging in the ageing brain are associated with future risks for functional dependence. SUBJECTS: 160 residents aged 69 years and older at the cranial CT and were independently living in a rural community in Hokkaido, Japan. METHODS: Cranial CT was performed between 1991 and 1993, graded for ventricular enlargement, sulcal enlargement, white matter change, and small infarction. Functional status was reassessed in 1998 in each participant. Multiple logistic regression analysis was performed to estimate the association of CT changes in the ageing brain with development of functional dependence over six years. RESULTS: Functional dependence was found in 19 residents at the second survey. After adjusting for age, sex, medical conditions, and cognitive functioning, small infarction and ventricular enlargement were significantly associated with development of functional dependence (adjusted odds ratio = 9.27 and 4.62). CONCLUSIONS: After controlling for age, the age-related changes on cranial CT have significant association on development of functional dependence.     

脑白质疏松症伴发痴呆的危险因素分析

目的：研究脑白质疏松症（LA）伴发痴呆和血管性痴呆（VD）的危险因素。方法：LA组137例,对照组52例。采用简易精神状态检查法（MMSE）评分标准分为痴呆组和非痴呆组;参照Hachinski缺血量表评分又分为VD、非血管性痴呆和混合性痴呆三组。全部病例详细询问病史并进行相关的实验室检查。采用Logistic回归单因素分析痴呆、VD的危险因素,逐步Logistic回归多因素分析痴呆、VD存在的独立危险因素。结果：单因素分析LA、高血压、心脏病、血糖和痴呆发生有关;高血压、脑血管病与VD发生有关。多因素分析LA和高血压与痴呆发生有关;脑血管病与VD发生有关。结论：LA用高血压可能是痴呆的独立危险因素,脑血管病可能是VD的独立危险因素。     

老年脑白质疏松症患者血清脂质及载脂蛋白水平变化

测定８５例老年脑白质疏松患者和８０例正常人的血清脂质，载脂蛋白，结果发现，脑白质疏松患者血清甘油三酯，载脂蛋白水平明显提高；高密度脂蛋白胆固醇，载脂蛋白Ａ１水平及ＡｐｏＡ１／ＡｐｏＢ比值明显降低。