缺血性脑白质高信号患者脑微出血的危险因素分析

目的 探讨缺血性脑白质高信号(White Matter Hyperintensities,WMH)患者脑微出血(Cerebral Microbleeds,CMBs)的危险因素,进一步明确WMH患者CMBs的严重程度与服用阿司匹林持续时间的相关性。方法连续收集2016年6月-2017年9月在首都医科大学附属北京朝阳医院神经内科住院、并经头部MRI证实的WMH患者,分为无CMBs组、轻度CMBs组和中重度CMBs组,收集所有患者的临床资料,分析CMBs的危险因素,并进一步将服用阿司匹林的WMH患者进行亚组分析。结果 本研究入组357例WMH患者,其中无CMBs组189例,轻度CMBs组94例,中重度CMBs组74例。3组间性别、急性缺血性卒中、高血压病史、既往缺血性卒中病史、入院舒张压、服用阿司匹林持续时间≥2 y、同型半胱氨酸水平及WMH的严重程度相比较有显著差异(P 0. 05)。将服用阿司匹林的WMH患者(263例)进行亚组分析,发现随着CMBs的严重程度增加,重度WMH患者所占比例逐渐增高,服用阿司匹林持续时间≥2 y的比例逐渐增加。结论 WMH的严重程度与WMH患者CMBs的严重程度相关;男性、高血压与服用阿司匹林持续时间≥2 y是WMH患者CMBs的危险因素,并且WMH患者服用阿司匹林的时间越长,CMBs越严重。     

急性缺血性卒中预后评分的研究进展

急性缺血性卒中对人类生命和健康的危害极大,其发病率和死亡率在我国疾病谱中一直
处于前三位,给患者及其家庭带来沉重的生活障碍和经济负担。若能够早期判断急性缺血性卒中患
者的预后,积极干预,可有效降低不良预后的风险。最近国内外学者一直致力于急性缺血性卒中预
后评分的研发及应用。本文就急性缺血性卒中预后评分研究现状做一综述,期待帮助临床神经科
医师在接诊急性缺血性卒中患者时,对患者预后进行快速评判并指导决策。     

院内缺血性卒中的诊疗现状与挑战

院内卒中是指因其他疾病住院的患者在住院期间发生的急性卒中,其中最常见的类型是缺血性卒中.与社区卒中相比,院内缺血性卒中的危险因素和发病机制更为复杂,除了栓塞、低灌注、高凝状态,医源性因素也是重要的致病原因之一.院内缺血性卒中患者的不良功能预后和死亡率均较社区患者显著增高,研究提示基础疾病较多、围手术期栓塞所致脑梗死范围...     

总胆固醇/高密度脂蛋白胆固醇比值与缺血性卒中复发关系研究

目的 探讨急性缺血性卒中90 d内复发与TC/HDL-C比值的关系。 方法 利用急性缺血性卒中患者氧化应激水平临床观察研究（Study on Oxidative Stress in Patients with Acute Ischemic Stroke,SOS-Stroke）数据库的3605例患者作为研究对象,采用多因素Logistic回归 分析急性缺血性卒中患者90 d卒中复发的影响因素。 结果 该研究人群中有231例（6.40%）患者90 d卒中复发,多因素Logistics回归结果显示：年龄（OR 1.02,95%CI 1.00～1.03,P =0.011）、糖尿病史（OR 1.44,95%CI 1.00～2.07,P =0.048）是卒中复发的 危险因素,住院期间服用降脂药物（OR 0.60,95%CI 0.40～0.90,P =0.012）则是卒中复发的保护因素, 急性缺血性卒中患者中TC/HDL-C比值不是卒中复发的预测因素。 结论 TC/HDL-C比值不能预测急性缺血性卒中90 d内复发的风险。     

急性腔隙性卒中患者血压的变异性及节律与脑白质高信号的相关性研究

目的 探索急性腔隙性卒中患者脑白质高信号与血压变异性及血压节律的关联。方法 回顾性纳入2017年1月-2019年1月于武汉市中西结合医院神经内科收治的急性腔隙性卒中患者156例,根据患者的头部MRI检查结果,采用Fazekas评分法将入组患者分为轻度白质病变组(n=76)和中重度白质病变组(n=80)。收集2组患者的一般信息、血管危险因素、实验室指标和其他检查结果,通过24 h ABPM获取血压变异性指标和血压节律,比较和分析影响急性腔隙性卒中患者WMH的相关因素。结果 中重度WMH组的既往卒中史(P=0.005)、急性腔隙性梗死灶数目(P=0.021)、颈动脉斑块等级积分(P=0.041)均高于轻度WMH组;中重度WMH组的全天SBP-SD(P=0.01)、日间SBP-SD(P=0.004)、日间SBP-CV(P=0.018)、日间DBP-SD(P=0.028)均明显升高;在两组血压昼夜节律比较中,中重度WMH组反杓型血压节律的比例显著升高(P=0.03),轻度WMH组杓型血压比例更高(P=0.045)。多因素Logistic回归分析发现,急性腔梗病灶数目(OR=2.114,95%C...     

脑灌注成像预测溶栓后出血转化风险的研究进展

出血转化是缺血性卒中的常见并发症之一,其中溶栓治疗导致继发性出血转化风险明显 增加是困扰临床医生的重要问题。目前认为血脑屏障的破坏在出血转化的发生中起到关键的作用。 近来研究显示,急性期的灌注影像检查对于出血转化高风险人群检出可能具有更高的敏感性和其 他优势。本文针对灌注成像在预测急性缺血性卒中患者溶栓后出血转化的研究进展方面做一综述。     

踝臂指数、臂踝脉搏波传导速度在缺血性卒中的研究进展

正外周动脉疾病(PAD)包括一系列由脑部、内脏器官和肢体结构和功能改变而导致的非冠状动脉综合征,即指除冠状动脉之外的主动脉及其分支动脉的狭窄、闭塞或瘤样扩张。缺血性卒中是指各种原因所致脑部血液供应障碍,导致局部脑组织缺血、缺氧坏死,从而出现相应神经功能缺损的一类综合征。PAD是急性缺血性卒中的重要危险因素。据报道~([1-2])在急性缺血性卒中患者中PAD的患病率高达40%以上,急性     

自主神经功能障碍对卒中后睡眠障碍的影响

目的 探讨急性脑卒中睡眠觉醒障碍的早期诊断与自主神经系统(ANS)功能障碍的关系。方法 本研究是一项横断面观察研究,使用Ewing试验评估ANS功能障碍的严重程度,并应用PSQI评分评估脑卒中后3个月的失眠程度。分析首次缺血性脑卒中后自主神经系统功能变化与睡眠障碍的相关性。将缺血性卒中患者的脑成像标志物与自主神经系统(ANS)功能障碍联系起来,分析缺血性卒中合并ANS功能障碍、睡眠障碍对预后的影响以及相关因素。结果 本研究共纳入52例急性缺血性脑卒中患者,其中男44例(84.6%),年龄(58.85±9.52)岁。ANS功能障碍的比例高达90.4%,10例(19.2%)严重ANS功能障碍患者在脑干卒中患者中睡眠障碍的发生率最高。经过3个月的随访,发现与非严重ANS功能障碍组相比,严重ANS功能障碍组的神经功能障碍和日常生活能力受损更严重,但未发现严重的ANS功能障碍与睡眠障碍之间的联系。结论 急性缺血性脑卒中普遍存在ANS功能障碍,尚未发现严重的ANS功能障碍与睡眠障碍之间的关系。ANS调节可能是急性缺血性脑卒中的一个治疗方向。     

机器学习基于不平衡数据预测急性新发缺血性卒中患者院内死亡模型研究

目的 探索利用机器学习基于不平衡数据预测急性新发缺血性卒中患者的院内死亡风险,并比较机器学习模型和传统logistic模型的预测性能.方法 以中国卒中联盟多中心登记数据库中急性新发缺血性卒中患者为研究对象,分别基于机器学习[XGBoost模型、CatBoost模型、随机森林模型、支持向量机(support vector...     

合并颅内外血管病变的缺血性卒中患者相关危险因素的回顾性研究

目的 研究卒中危险因素在缺血性卒中合并/不合并颅内/外大血管病变患者中的分布.方法 根据头部血管影像学(B超、CTA、MRA及DSA)对304例急性缺血性卒中患者是否合并有责任的大血管狭窄进行分组,回顾性分析在不同分组间各个危险因素的差异及相对危险度.结果 对比腔隙性缺血性卒中(lacunar stroke,Lac-s),年龄>65岁的患者发生大动脉粥样硬化性缺血性卒中(large artery artherosclerosis stroke,LAA-s)的风险增高2倍;在吸烟人群中,这种风险增高2.3倍,血糖稳定机制异常患者发生LAA-s的风险比Lac-s高近2.8倍,而糖尿病人群中这种风险增高2.3倍,其他卒中危险因素在两组间的分布未见统计学差异(P>0.05).在缺血性卒中合并责任和非责任大血管病变间,各种危险因素分布无差别.在缺血性卒中合并颅外责任血管病变(Stroke with extracranial artery artheroscloerosis,ECAA-s)组和合并颅内责任血管病变(Stroke with intracranial artery artheroscloerosis,ICAA-s)组间,男性与ECAA-s组相关性更加密切(P=0.001,OR=0.15),男性发生ECAA-s的风险是发生ICAA-s的6.7倍;血糖增高的患者显示出ICAA-s的高风险(P=0.012,OR=2.61).结论 年龄>65岁、吸烟和糖尿病患者更容易发生大动脉粥样硬化性缺血性卒中;血糖的异常增高带来缺血性卒中合并颅内大血管风险的增高,男性卒中患者更加容易发生颅外大血管责任性病变.     

Higher blood–brain barrier permeability is associated with higher white matter hyperintensities burden

The pathogenesis of white matter hyperintensities (WMH) is incompletely understood but blood–brain barrier (BBB) dysfunction may play a key role. This study aimed to investigate the relationship between BBB permeability and the severity of WMH burden. Consecutive participants without symptomatic stroke history presented for physical examination were recruited in this cross-sectional study and divided into three WMH burden groups according to total Fazekas scores. They received dynamic contrast-enhanced-magnetic resonance imaging to measure BBB permeability, and received Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). A total of 102 participants aged 49–90 years (mean age of 69.82 years) were enrolled (36 with low WMH burden, 35 with medium WMH burden, and 31 with high WMH burden). Multivariable linear regression analyses revealed that participants with higher WMH burden had significantly higher BBB leakage rate and area under the leakage curve in normal-appearing white matter, WMH, cortical gray matter, and deep gray matter (DGM) after adjustment for age, sex, and vascular risk factors. Scores on MMSE and MoCA decreased with increasing leakage rate in WMH and DGM after adjustment for age, sex, WMH burden, and education years. We found that higher BBB permeability is associated with higher WMH burden and cognitive decline. The compromised BBB integrity may be a critical contributor to the pathogenesis of WMH and part of a series of pathological processes that finally lead to cognitive impairment.     

Cerebral white matter hyperintensities on MRI: Current concepts and therapeutic implications

BACKGROUND: White matter hyperintensities (WMH) are commonly observed MRI abnormalities in the elderly, which generally reflect covert vascular brain injury. WMH cumulatively produce substantial neurologic, psychiatric, and medical morbidity. This review provides an overview of current knowledge on vascular WMH, and describes some pharmacological agents that may have a role in mitigating this condition. SUMMARY OF REVIEW: This review has two main focus areas. The first is a discussion of currently available knowledge regarding the public health burden, pathogenesis, and various risk factors associated with the presence of vascular white matter lesions noted on brain MRI. The second section of the article details the mechanistic and clinical basis for promising pharmacological treatment modalities that could potentially prevent progression of ischemic cerebral white matter brain injury. Many of these therapies are already of proven efficacy in preventing recurrent stroke. CONCLUSIONS: Individuals with vascular white matter lesions on MRI may represent a potential target population likely to benefit from secondary stroke prevention therapies.     

Cornea: A Window to White Matter Changes in Stroke; Corneal Confocal Microscopy a Surrogate Marker for the Presence and Severity of White Matter Hyperintensities in Ischemic Stroke

PurposeThe presence of white matter hyperintensities (WMH) on MRI imaging confers an increased risk of stroke, dementia, and death. Corneal confocal microscopy (CCM) can detect nerve injury non-invasively and may be a useful surrogate marker for WMH. The objective is to determine whether corneal nerve pathology identified using CCM is associated with the presence of WMH in patients with acute ischemic stroke.MethodsThis is a cross-sectional study where 196 consecutive individuals with acute ischemic stroke were enrolled and underwent neurological examination, MRI brain imaging and CCM. Participants underwent blinded quantification of WMH and corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD) and corneal nerve fiber length (CNFL).ResultsThe prevalence of hypertension [P = .013] was significantly higher and CNFD [P = .031] was significantly lower in patients with WMH compared to those without WMH. CNFD and CNFL were significantly lower in patients with DM without WMH [P = .008, P = .019] and in patients with DM and WMH [P = .042, P = .024] compared to patients without DM or WMH, respectively. In a multivariate model, a 1-unit decrease in the CNFD increased the risk of WMH by 6%, after adjusting for age, DM, gender, dyslipidemia, metabolic syndrome, smoking, and HbA1c. DM was associated with a decrease in all CCM parameters but was not a significant independent factor associated with WMH.ConclusionsCCM demonstrates corneal nerve pathology, which is associated with the presence of WMH in participants with acute ischemic stroke. CCM may be a useful surrogate imaging marker for the presence and severity of WMHs.     

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.     

Small vessel disease burden predicts functional outcomes in patients with acute ischemic stroke using machine learning

Aims

Our purpose is to assess the role of cerebral small vessel disease (SVD) in prediction models in patients with different subtypes of acute ischemic stroke (AIS).

Methods

We enrolled 398 small-vessel occlusion (SVO) and 175 large artery atherosclerosis (LAA) AIS patients. Functional outcomes were assessed using the modified Rankin Scale (mRS) at 90 days. MRI was performed to assess white matter hyperintensity (WMH), perivascular space (PVS), lacune, and cerebral microbleed (CMB). Logistic regression (LR) and machine learning (ML) were used to develop predictive models to assess the influences of SVD on the prognosis.

Results

In the feature evaluation of SVO-AIS for different outcomes, the modified total SVD score (Gain: 0.38, 0.28) has the maximum weight, and periventricular WMH (Gain: 0.07, 0.09) was more important than deep WMH (Gain: 0.01, 0.01) in prognosis. In SVO-AIS, SVD performed better than regular clinical data, which is the opposite of LAA-AIS. Among all models, eXtreme gradient boosting (XGBoost) method with optimal index (OI) has the best performance to predict excellent outcome in SVO-AIS. [0.91 (0.84–0.97)].

Conclusions

Our results revealed that different SVD markers had distinct prognostic weights in AIS patients, and SVD burden alone may accurately predict the SVO-AIS patients' prognosis.     

Superficial white matter microstructure affects processing speed in cerebral small vessel disease

White matter hyperintensities (WMH) are a typical feature of cerebral small vessel disease (CSVD), which contributes to about 50% of dementias worldwide. Microstructural alterations in deep white matter (DWM) have been widely examined in CSVD. However, little is known about abnormalities in superficial white matter (SWM) and their relevance for processing speed, the main cognitive deficit in CSVD. In 141 CSVD patients, processing speed was assessed using Trail Making Test Part A. White matter abnormalities were assessed by WMH burden (volume on T2‐FLAIR) and diffusion MRI measures. SWM imaging measures had a large contribution to processing speed, despite a relatively low SWM WMH burden. Across all imaging measures, SWM free water (FW) had the strongest association with processing speed, followed by SWM mean diffusivity (MD). SWM FW was the only marker to significantly increase between two subgroups with the lowest WMH burdens. When comparing two subgroups with the highest WMH burdens, the involvement of WMH in the SWM was accompanied by significant differences in processing speed and white matter microstructure. Mediation analysis revealed that SWM FW fully mediated the association between WMH volume and processing speed, while no mediation effect of MD or DWM FW was observed. Overall, results suggest that the SWM has an important contribution to processing speed, while SWM FW is a sensitive imaging marker associated with cognition in CSVD. This study extends the current understanding of CSVD‐related dysfunction and suggests that the SWM, as an understudied region, can be a potential target for monitoring pathophysiological processes.     

Cerebral white matter hyperintensities in the prediction of cognitive decline and incident dementia

Abstract

Cerebral white matter hyperintensities (WMH), detected in vivo with magnetic resonance imaging (MRI), are commonly used to assess cerebrovascular burden in cognitive impairment. However, the association between WMH and cognition is not consistent across the literature. The present review examines evidence from published longitudinal studies. We reviewed the PubMed data base from January 1990 to March 2013 and included studies investigating the association of WMH with (1) the risk of dementia in the general population, (2) the risk of conversion to dementia in the mild cognitive impairment (MCI) population, and (3) cognitive decline in the general population. WMH were associated with all types of dementia in the general population, but not in MCI patients. Results are discrepant for global decline. WMH appear to be early predictors of the risk of dementia, but this association appears to be modulated by cognitive reserve, age and the spatial distribution of lesions. There are, however, some limits in the use of WMH as a marker of vascular burden. In addition to their ischaemic origin, WMH may be the result of co-occurring morbidity. Further research is needed to elucidate to what extent WMH actually reflect vascular risk to evaluate the likely efficacy of interventions specifically targeting WMH reduction.     

Cardiovascular risk factors and small vessel disease of the brain: Blood pressure,white matter lesions,and functional decline in older persons

Several potential vascular risk factors exist for the development and accumulation of subcortical white matter disease in older people. We have reported that in older people followed for up to 4 years white matter hyperintensity (WMH) lesions on magnetic resonance imaging nearly doubled in volume and were associated with alterations in mobility and cognitive function. Herein we review the genetic, metabolic, and vascular risk factors that have been evaluated in association with the development and pathogenesis of WMH in older persons. Our research efforts have focused on systemic hypertension, particularly in the out-of-office setting as 24-hour ambulatory blood pressure (BP) has proven to be a stronger indicator of the progression of WMH in older people and the associated functional decline than doctor’s office BP. Based on relations between 24-hour systolic BP levels, the accrual of WMH, and functional decline, we have designed the INFINITY trial, the first interventional study to use ambulatory BP to guide antihypertensive therapy to address this problem in the geriatric population.     

Adaptive metabolic changes in CADASIL white matter

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an important genetic cause of stroke, but pathogenic mechanisms and functional alterations remain poorly characterized. The purpose of this study was to investigate adaptive metabolic and functional changes in white matter hyperintensities and normal-appearing white matter in CADASIL patients using ¹H-magnetic resonance spectroscopic imaging (MRSI). Eight CADASIL patients and eight matched healthy controls were studied. ¹H-MRSI data were acquired on a 3T scanner using high-resolution multi-spin echo spectroscopic imaging (T _E = 288 ms) and non-accelerated medium-resolution MRSI (T _E = 35 ms). MRI of all CADASIL patients demonstrated characteristic white matter hyper-intensities (WMH) in the subcortical periventricular white matter. Cre/Cho, Glx/Cho and Glx/Cre ratios were significantly decreased in WMH compared to normal-appearing white matter (NAWM) in patients, while Glx/Cre and mI/Cho ratios in NAWM showed a significant increase compared to healthy controls. In severely affected patients derived spectra reflected a decrease of NAA concentrations inside WMH when compared to healthy white matter. Metabolic abnormalities in WMH of CADASIL patients are compatible with axonal loss due to chronic micro-infarctions. Increased Glx/Cre and mI/Cho ratios in NAWM indicate an augmented glial cell density and decreased neuronal cell density. This altered tissue composition might be interpreted as adaptation to hypoperfusion and impaired vasoreactivity in NAWM of CADASIL patients. Our data might contribute to the general understanding of adaptive processes induced by hypoperfusion and chronic ischemia.     

White matter hyperintensities correlate to cognition and fiber tract integrity in older adults with HIV

Our aim was to examine the clinical relevance of white matter hyperintensities (WMH) in HIV. We used an automated approach to quantify WMH volume in HIV seropositive (HIV+; n = 65) and HIV seronegative (HIV?; n = 29) adults over age 60. We compared WMH volumes between HIV+ and HIV? groups in cross-sectional and multiple time-point analyses. We also assessed correlations between WMH volumes and cardiovascular, HIV severity, cognitive scores, and diffusion tensor imaging variables. Serostatus groups did not differ in WMH volume, but HIV+ participants had less cerebral white matter (mean: 470.95 [43.24] vs. 497.63 [49.42] mL, p = 0.010). The distribution of WMH volume was skewed in HIV+ with a high proportion (23%) falling above the 95th percentile of WMH volume defined by the HIV? group. Serostatus groups had similar amount of WMH volume growth over time. Total WMH volume directly correlated with measures of hypertension and inversely correlated with measures of global cognition, particularly in executive functioning, and psychomotor speed. Greater WMH volume was associated with poorer brain integrity measured from diffusion tensor imaging (DTI) in the corpus callosum and sagittal stratum. In this group of HIV+ individuals over 60, WMH burden was associated with cardiovascular risk and both worse diffusion MRI and cognition. The median total burden did not differ by serostatus; however, a subset of HIV+ individuals had high WMH burden.