Stroke：降血压治疗对脑白质高信号的作用

正脑小血管病(small vessel disease,SVD)是一个复合术语,神经影像上脑小血管损害是其特征,包括白质高信号(white matter hyperintensities,WMH)、腔隙、微出血、血管周围间隙扩大、急性皮层下小梗死和脑萎缩。随着严重程度的增加,SVD与认知功能和步态障碍有关。高血压是脑小血管病的重要危险因素。抗高血压药物(antihypertensive medication,     

缺血性卒中后白质微血管完整性的性别特异性差异

Stroke and Vascular Neurology(SVN)2019年12月上线文章“Sex-specific differences in white matter microvascular integrity after ischemic stroke”,由美国哈佛大学医学院附属麻省总医院神经内科Mark R Etherton等完成。作者回顾分析了105例男性和79例女性急性缺血性卒中患者的影像学资料。     

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.     

Prestroke Statins,Progression of White Matter Hyperintensities,and Cognitive Decline in Stroke Patients with Confluent White Matter Hyperintensities

Cerebral white matter hyperintensities (WMH) are a consequence of cerebral small vessel disease. Statins have been shown to reduce recurrent stroke among patients with various stroke subtypes, including lacunar stroke, which also arises from small vessel disease. In this study, we investigated the hypothesis that prestroke statin use would reduce the progression of WMH and/or cognitive decline among stroke patients with confluent WMH. Patients (n?=?100) were participants of the VITAmins To Prevent Stroke magnetic resonance imaging substudy. All patients had confluent WMH on magnetic resonance imaging at baseline. Eighty-one patients completed the 2-year follow-up. We assessed general cognition and executive function using the mini-mental state examination and Mattis dementia rating scale–initiation/perseveration subscale, respectively. We compared the change in volume of WMH and cognition between prestroke statin use and prestroke nonstatin use groups. We also evaluated the effects of prestroke statin use on incident lacunes and microbleeds. The prestroke statin use group (n?=?51) had less WMH volume progression (1.54?±?4.52 cm³ vs 5.01?±?6.00 cm³, p?=?0.02) compared with the prestroke nonstatin use group (n?=?30). Multivariate linear regression modeling identified prestroke statin use as an independent predictor of WMH progression (β?=?–0.31, p?=?0.008). Prestroke statin use was also associated with less decline (Mattis dementia rating scale–initiation/perseveration subscale; β?=?0.47, p?=?0.001). No association was observed with changes in mini-mental state examination scores. There were no between group differences on incident lacunes or incident microbleeds. Prestroke statin use may reduce WMH progression and decline in executive function in stroke patients with confluent WMH.     

Prestroke Statins,Progression of White Matter Hyperintensities,and Cognitive Decline in Stroke Patients with Confluent White Matter Hyperintensities

Cerebral white matter hyperintensities (WMH) are a consequence of cerebral small vessel disease. Statins have been shown to reduce recurrent stroke among patients with various stroke subtypes, including lacunar stroke, which also arises from small vessel disease. In this study, we investigated the hypothesis that prestroke statin use would reduce the progression of WMH and/or cognitive decline among stroke patients with confluent WMH. Patients (n = 100) were participants of the VITAmins To Prevent Stroke magnetic resonance imaging substudy. All patients had confluent WMH on magnetic resonance imaging at baseline. Eighty-one patients completed the 2-year follow-up. We assessed general cognition and executive function using the mini-mental state examination and Mattis dementia rating scale–initiation/perseveration subscale, respectively. We compared the change in volume of WMH and cognition between prestroke statin use and prestroke nonstatin use groups. We also evaluated the effects of prestroke statin use on incident lacunes and microbleeds. The prestroke statin use group (n = 51) had less WMH volume progression (1.54 ± 4.52 cm³vs 5.01 ± 6.00 cm³, p = 0.02) compared with the prestroke nonstatin use group (n = 30). Multivariate linear regression modeling identified prestroke statin use as an independent predictor of WMH progression (β = –0.31, p = 0.008). Prestroke statin use was also associated with less decline (Mattis dementia rating scale–initiation/perseveration subscale; β = 0.47, p = 0.001). No association was observed with changes in mini-mental state examination scores. There were no between group differences on incident lacunes or incident microbleeds. Prestroke statin use may reduce WMH progression and decline in executive function in stroke patients with confluent WMH.

Electronic supplementary material

The online version of this article (doi:10.1007/s13311-014-0270-5) contains supplementary material, which is available to authorized users.     

卒中后轻度认知功能障碍与脑白质病变的研究

脑白质病变,在影像学中又称为脑白质疏松症,是脑微血管病变的一种重要类型。有大量研究表明,卒中后轻度认知功能障碍与脑白质病变存在明显的相关性。弥散张量成像对白质纤维的显示具有一定的优势,成为卒中后认知功能障碍研究的重要工具。本文对近年来卒中后认知功能障碍与脑白质病变的相关研究予以综述。     

Neurodevelopmental and Neurodegenerative Models of Schizophrenia: White Matter at the Center Stage

Schizophrenia is a disorder of cerebral disconnectivity whose lifetime course is modeled as both neurodevelopmental and neurodegenerative. The neurodevelopmental models attribute schizophrenia to alterations in the prenatal-to-early adolescent development. The neurodegenerative models identify progressive neurodegeneration as its core attribute. Historically, the physiology, pharmacology, and treatment targets in schizophrenia were conceptualized in terms of neurons, neurotransmitter levels, and synaptic receptors. Much of the evidence for both models was derived from studies of cortical and subcortical gray matter. We argue that the dynamics of the lifetime trajectory of white matter, and the consistency of connectivity deficits in schizophrenia, support white matter integrity as a promising phenotype to evaluate the competing evidence for and against neurodevelopmental and neurodegenerative heuristics. We develop this perspective by reviewing normal lifetime trajectories of white and gray matter changes. We highlighted the overlap between the age of peak of white matter development and the age of onset of schizophrenia and reviewed findings of white matter abnormalities prior to, at the onset, and at chronic stages of schizophrenia. We emphasized the findings of reduced white matter integrity at the onset and findings of accelerated decline in chronic stages, but the developmental trajectory that precedes the onset is largely unknown. We propose 4 probable lifetime white matter trajectory models that can be used as the basis for separation between the neurodevelopmental and neurodegenerative etiologies. We argue that a combination of the cross-sectional and longitudinal studies of white matter integrity in patients may be used to bridge the neurodevelopment and degeneration heuristics to advance schizophrenia researchKey words: white matter integrity, etiology of schizophrenia, diffusion tensor imaging     

缺血性卒中合并脑白质病变的危险因素研究

目的 探讨缺血性卒中合并脑白质病变的患病情况及相关危险因素,通过对其干预以降低脑白质病变的发生率。方法 本研究连续入选2007年8月至2008年10月在北京天坛医院神经内科住院的缺血性卒中患者共483例,依据有无脑白质病变分成伴脑白质病变组和无白质病变两组,得出我院住院的缺血性卒中患者合并脑白质病变的患病率,以有无脑白质病变作为因变量,各种血管病危险因素作为自变量进行Logistic回归多因素分析。结果 我院住院的缺血性卒中患者脑白质病变的患病率为53.8%,随年龄增长发生率和病变严重程度增加（P均<0.01）。Logistic回归显示高龄［比值比（odds ratio,OR）=1.03,95%可信区间（confidence interval,CI）1.00～1.05,P<0.05］、高血压病（OR=1.77,95%CI 1.07～2.91,P<0.05）、卒中病史（OR=1.71,95%CI 1.02～2.88,P<0.05）、高血糖（OR=1.07,95%CI 1.00～1.15,P<0.05）和腔隙性脑梗死（OR=1.89,95%CI 1.17～3.06,P<0.05）是脑梗死患者合并脑白质病变的独立危险因素。结论 随年龄增长,脑白质病变的患病率和严重程度增加;高龄、高血压病、卒中病史、高血糖和腔隙性脑梗死是缺血性卒中患者合并脑白质病变的独立危险因素。     

脑小血管病脑白质损伤动物模型

脑小血管病是导致认知功能减退、步态情感障碍和痴呆的重要脑血管疾病,脑白质弥漫 性损伤是该病的重要影像学特征。结合国内外近年来相关研究内容,本文对不同的脑小血管病白质 损伤动物模型制作进行了系统性回顾,包括单一型动物模型如双侧颈总动脉狭窄模型、脑淀粉样血 管病模型、Notch3 转基因小鼠模型、自发性高血压大鼠模型、易卒中型肾血管性高血压大鼠模型,以 及由两个或两个以上单一型动物模型组合而成的复合型动物模型等。     

Prospectively Collected Cardiovascular Biomarkers and White Matter Hyperintensity Volume in Ischemic Stroke Patients

Background: Few prospective cohort studies collect detailed information on stroke characteristics among individuals who experience ischemic stroke, including white matter hyperintensity volume, and thus cannot explore how prospectively collected biomarkers prior to the stroke influence white matter hyperintensity volume. We explored the association between a large panel of prospectively collected lipid and inflammatory biomarkers and white matter hyperintensity volume among participants in the Women's Health Study with incident ischemic stroke. Methods: Among Women's Health Study participants with first ischemic stroke who had baseline serum biomarkers and available magnetic resonance imaging, we measured white matter hyperintensity volume using a validated semi-automated method. Linear regression was used to explore the associations between biomarkers and log-transformed white matter hyperintensity volume. Results: After multivariate adjustment, a 1% increment in HbA1c% was associated with an increase in white matter hyperintensity volume (P value = .05). Evidence of a nonlinear association between high density lipoprotein cholesterol levels and ApoA1 levels with white matter hyperintensity volume was noted (P values for nonlinearity = .01 and .001, respectively). No other biomarkers were significantly associated with white matter hyperintensity volume. Conclusions: Chronic hyperglycemia as evidenced by HbA1c levels measured years prior to stroke is associated with white matter hyperintensity volume at the time of stroke. Additional research is needed to explain why low levels of high density lipoprotein cholesterol levels and ApoA1 may be associated with similar white matter hyperintensity volume as high levels.     

脑白质病变临床特点与白质传导束关系研究进展

脑白质病变(WML)是脑小血管病的一种,与年龄、高血压等血管危险因素相关。WML与脑卒中、记忆、语言、步态及情绪等有密切联系,而且其进展预示着临床预后较差。利用MR微细结构成像技术了解到脑白质传导束的病变与其多样化的临床表现相关。MRI技术为WML的病理生理机制提供了依据,为进一步了解WML多样化临床表现提供了新视角。     

急性缺血性卒中患者血尿酸水平与脑白质病变的相关性研究

目的 探讨急性缺血性卒中患者血尿酸水平与脑白质病变（white matter lesions,WMLs）的相关性。 方法 连续入选2011年1月～2012年12月发病48 h内的首发缺血性卒中患者进行横断面研究,按 照Ylikoski评分将患者分为两组：重度WMLs组、无或轻度WMLs组。比较两组患者血糖、甘油三酯 （triglyceride,TG）、总胆固醇（total cholesterol,TC）、低密度脂蛋白-胆固醇（low density lipoproteincholesterol, LDL-C）、高密度脂蛋白-胆固醇（high density lipoprotein-cholesterol,HDL-C）及血尿酸水 平,并行Logistic回归分析重度WMLs危险因素。 结果 共入选急性缺血性卒中患者321例,其中重度WMLs组159例,无或轻度WMLs组162例。重度 WMLs组患者年龄（P＜0.001）、糖尿病发生率（P =0.011）、血糖（P＜0.001）、血尿酸水平（P＜0.001）、 高尿酸血症发生率（P =0.002）均高于无或轻度WMLs组（P均＜0.05）,两组性别、高血压发生率、收 缩压、舒张压、心房颤动发生率、血TG、TC、LDL-C、HDL-C水平、吸烟史比例无显著差异。校正年 龄、性别、血压、伴发高血压、糖尿病、心房颤动、血糖、血脂及吸烟史后,年龄［比值比（odds ratio, OR）1.062,95%可信区间（confidence interval,CI）1.0008～1.119,P =0.023］、血尿酸水平（OR 1.531, 95%CI 1.186～1.975,P =0.001）和高尿酸血症（OR 1.131,95%CI 1.047～1.222,P =0.002）是急性缺血 性卒中患者发生重度WMLs的独立危险因素。 结论 血尿酸水平和高尿酸血症是急性缺血性卒中患者伴发重度WMLs的独立危险因素     

Novel Protective Effects of Histone Deacetylase Inhibition on Stroke and White Matter Ischemic Injury

Understanding how epigenetics influences the process and progress of a stroke could yield new targets and therapeutics for use in the clinic. Experimental evidence suggests that inhibitors of zinc-dependent histone deacetylases can protect neurons, axons, and associated glia from the devastating effects of oxygen and glucose deprivation. While the specific enzymes involved have yet to be clearly identified, there are hints from somewhat selective chemical inhibitors and also from the use of specific small hairpin RNAs to transiently knockdown protein expression. Neuroprotective mechanisms implicated thus far include the upregulation of extracellular glutamate clearance, inhibition of p53-mediated cell death, and maintenance of mitochondrial integrity. The histone deacetylases have distinct cellular and subcellular localizations, and discrete substrates. As a number of chemical inhibitors are already in clinical use for the treatment of cancer, repurposing for the stroke clinic should be expedited.