Comparison of the pathology of cerebral white matter with post-mortem magnetic resonance imaging (MRI) in the elderly brain

White matter lesions (WML) on magnetic resonance imaging (MRI) brain scans are associated with ageing. They are unrelated to specific disorders, and their impact on cognitive and other brain functions is poorly characterized. Pathological studies often omit systematic survey of WML because of the need to study multiple full coronal tissue blocks, and uncertainty over the significance of lesions identified in periventricular and deep subcortical regions. Post-mortem MRI provides a means of mapping WML but the sensitivity and specificity of the method are unresolved. In this study post-mortem MRI of WML in fixed brain slices was compared with pathology in 33 brains donated to the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS). This study shows that MRI detection of WML was less sensitive than pathology: periventricaular lesions (PVL) sensitivity = 95% (87-99%), specificity = 71% (44-90%); deep subcortical lesions (DSCL) sensitivity = 86% (79-93%), specificity = 80% (72-88%). False negative MRI was associated with milder pathology, but lesions detected by myelin attenuation alone showed both microglial and endothelial activation. Therefore post-mortem MRI of formalin-fixed brain slices is a reliable method to obtain systematic data on the severity and distribution of cerebral white matter disease, and appears to detect those WML most likely to have clinical impact.     

White matter hyperintensities and rating scales—observer reliability varies with lesion load

Abstract.Background: Cerebral white matter hyperintensities (WMHs) are common in older people. Their presence correlates with cognitive decline and vascular risk factors. Various scales have been developed to quantify the amount and type of WMH, but with few observer reliability studies. We evaluated several scales in different cohorts to determine their observer reliability.Methods: Two observers independently rated T2-weighted MR images from five groups (total n = 494: normal older subjects [97]; patients with minor stroke [221]; young insulin dependent diabetics [141]; maturity onset diabetics [10]; and hepatic encephalopathy [25]), using seven rating scales (Breteler, Fazekas, Longstreth, Mirsen, Shimada, Van Swieten and Wahlund). Inter-observer reliability was determined using Kappa statistics.Results: Patients with maturity onset diabetes had the most WMHs and young insulin-dependent diabetics the least. Inter-observer reliability varied with the amount of WMH. In maturity onset diabetics (most WMHs) the weighted Kappas were: Breteler 0.74; Fazekas 0.89 and 0.72; Van Swieten 0.76 and 0.88; and in young insulin-dependent diabetics (least WMH): Breteler 0.3; Fazekas 0.2 and 0.24; Van Swieten 0.39 and 0.30. These findings were consistent across the groups.Conclusion: WMH rating scale performance varied with WMH prevalence, and hence with subject cohort. In patients with most WMHs the apparent better kappas may reflect a ceiling effect rather than true better agreement. These factors should be considered in studies where risk factors for, or associations with, the early development of WMHs are being determined.     

皮质下缺血性血管病患者平均血小板体积水平变化及其意义

目的 探讨皮质下缺血性血管病(SIVD)患者平均血小板体积(MPV)水平的变化及其意义.方法 选取340例SIVD患者(SIVD组)和同期健康体检者(对照组)160例,根据头颅MRI将SIVD组分为多发性腔隙性脑梗死(LI)组(n=124)和脑白质疏松(LA)组(n=216),按照Fazekas的评分标准将LA组LA严重程度分为3级;采用血液分析仪检测所有受试者MPV值,比较SIVD组及其亚组与对照组之间MPV水平的变化,并分析MPV与LA程度的相关性.结果SIVD组MPV水平显著高于对照组,差异有统计学意义(P<0.01).在校正年龄因素后,LI组和LA组MPV水平均显著高于对照组,差异有统计学意义(P<0.01),且LA组MPV水平显著高于LI组,差异有统计学意义(P<0.05).将LA组进一步分组后显示,LA等级越高者,MPV水平越高,差异有统计学意义(P<0.05);相关分析显示,MPV水平与LA等级呈显著正相关性(rs=0.596,P<0.01).多元回归分析显示,在控制各项危险因素后,MPV水平与SIVD的发病仍密切相关(OR=3.461,95%CI:2.653~4.515,P<0.01).结论 MPV增高可能是SIVD的独立危险因素,且MPV水平与LA严重程度密切相关.     

孤立性侧脑室后角旁白质疏松对认知功能的影响及其神经心理特征

目的 探讨孤立性侧脑室后角旁白质疏松对认知功能的影响及其神经心理特征.方法 纳入30例孤立性侧脑室后角旁白质疏松(后角组)、32例大脑半球多部位白质疏松(混合组)以及33例颅脑MRI证实无脑实质结构性改变的受试者(对照组),采用简易精神状态量表(mini-mental state examination scale,MMSE)和蒙特利尔认知评估量表(Montreal cognitive assessment,MoCA,北京版),评价受试者总体认知功能,韦氏成人智力量表中数字广度测验分项目评估注意能力,临床记忆量表评估记忆能力,对比分析侧脑室后角旁白质疏松所致认知损害特征.结果 与对照组比较,后角组MMSE和MoCA总分较低(P＜0.01),定向力、短时记忆、延迟记忆、指向记忆和语言测试单项评分也明显降低(P ＜0.05,P＜0.01),而其他认知方面单项评分差异无统计学意义(P＞0.05);混合组MMSE和MoCA总分较低(P＜0.01),定向力、记忆力、注意能力、视觉空间与执行、语言测试和抽象认知单项评分也明显降低(P ＜0.05,P＜0.01).结论 孤立性侧脑室后角旁白质疏松导致以定向力、记忆力和语言能力减退为特征的认知功能损害.     

脑白质疏松症对脑梗塞患者康复的影响

目的探讨脑白质疏松症对脑梗塞后神经功能状态的影响.方法选择1994-1999年间79例合并脑白质疏松症的脑梗塞患者,并按1∶1配对原则,以年龄及性别相匹配的无脑白质疏松症的脑梗塞患者进行病例对照研究,比较两组患者入院及康复3个月时的神经功能状态积分,并进行多因素Logistic回归分析.结果两组患者入院时神经功能积分无显著性差异(P＞0.05),但康复3个月时合并脑白质疏松症的脑梗塞患者神经功能积分明显高于对照组(P＜0.01);对高血压病、冠心病及吸烟史等因素调整后,脑白质疏松症仍独立于其他因素影响脑梗塞康复3个月时的神经功能结果(r=0.43,P＜0.05).结论脑白质疏松症可能影响脑梗塞患者神经功能的康复.     

Population-specific spectrum of <Emphasis Type="Italic">NOTCH3</Emphasis> mutations,MRI features and founder effect of CADASIL in Chinese

Background and purpose   Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary disorder caused by NOTCH3 mutations and characterized by recurrent subcortical infarctions, dementia and leukoencephalopathy. So far, most clinical, molecular and neuroimaging information has come from Caucasians. Therefore, we investigated the spectrum of NOTCH3 mutations and MRI features in CADASIL patients of Chinese origin on Taiwan. Methods   Mutational analysis of NOTCH3 exons 2 to 23 by direct nucleotide sequencing was performed in patients with clinically suspected CADASIL. MRI findings were retrospectively evaluated and scored using a modified Schelten’s scale. Results   Nine different point mutations of NOTCH3 were identified in 21 unrelated patients. Intriguingly, 47.6 % were in exon 11, and 19 % in each of exon 4 and 18. R544C was very common and present in all patients with a mutation in exon 11. Many patients with NOTCH3 R544C share the same haplotype linked to the mutation using markers D19S929 and D19S411, which flank the NOTCH3. The sensitivity of T2-weighted MRI detecting anterior temporal abnormality was only 42.9 %. Furthermore, the neuroimaging evidence of intracerebral hemorrhage (ICH) was present in 23.8 % of the 21 patients. Conclusions   A population-specific mutational spectrum of CADASIL was found in the Chinese patients on Taiwan. The Chinese patients carrying NOTCH3 R544C may descend from a common ancestor. Anterior temporal hyperintensity on T2-weighted MRI may not be a sensitive marker for CADASIL. ICH is a relatively common manifestation of CADASIL in East Asians, especially in the presence of hypertension.     

Leukoaraiosis is associated with arterial wall thickness: A quantitative analysis

Leukoaraiosis refers to an age‐related, abnormal appearance of the brain white matter on neuroimaging. The association between leukoaraiosis and cerebrovascular disease suggests that ischemia may be an important contributing factor; however, the pathogenesis of the condition remains controversial. We hypothesized that physical abnormalities of blood vessels might be culpable and compared the external and internal measurements of blood vessel walls between brains that demonstrated leukoaraiosis on imaging and normal control brains. Fourteen brains of individuals who had been diagnosed as having severe leukoaraiosis and five non‐leukoaraiosis control brains were studied. Arterial cross‐sections were evaluated by length measurements with an image analysis device. Arterial wall thickness and the ratio of the outer and inner diameters of the vessel were measured. We measured a total of 108 vessels in the leukoaraiosis group and 95 vessels in the control group. The vessel walls of the leukoaraiosis patients were an average of 5.5 µm thicker than the walls of control vessels of the same inside diameter (P = 0.0000, 95% CI 3.01–8.08) and an average of 2.3 µm thicker than walls of control vessels of the same outside diameter (P = 0.016, 95% CI 0.48–4.17). Our data provide evidence that leukoaraiosis is associated with vessel wall thickening in an additive fashion and indicate that structural vascular abnormalities are associated with leukoaraiosis.     

Correlations between MRS and DTI in cerebral small vessel disease

Cerebral small vessel disease results in lacunar infarcts and cognitive impairment. Diffusion tensor imaging (DTI) demonstrates a reduction in fractional anisotropy and increase in mean diffusivity, which correlates more strongly with cognition than conventional MRI. The underlying pathological basis for these DTI changes is not known. In this study magnetic resonance spectroscopy was used to determine the biochemical basis of these DTI alterations. Twenty-five patients with lacunar stroke and radiological leukoaraiosis were recruited. Chemical shift imaging (CSI) and DTI were performed on a 1.5 T MRI scanner. A region of interest was positioned in the white matter of the centrum semiovale. Multivoxel CSI data were processed and the metabolite ratios estimated. DTI parameters corresponding to the exact region of tissue excited by CSI were obtained. Mean spectroscopy data and DTI values for each subject were correlated. Univariate analysis revealed a positive correlation between N-acetyl aspartate-creatine (NAA/Cr) and fractional anisotropy (r = 0.52, p = 0.008), and a negative correlation with mean diffusivity (r = -0.51, p = 0.009). Results remained little changed after controlling for mean percentage lesion and mean percentage white matter per voxel (with fractional anisotropy r = 0.54, p = 0.008, and with mean diffusivity r = -0.52, p = 0.01). These findings are consistent with axonal loss or dysfunction, or both, accounting for at least part of the DTI abnormalities found in patients with small vessel disease. It provides evidence that DTI identifies axonal disruption in white matter tracts.     

脑白质疏松轻度认知障碍证候学研究

目的探讨脑白质疏松轻度认知障碍(LACI)的主要证候要素,为该病的辨证论治提供依据。方法设计前瞻性观察方案,选取脑白质疏松轻度认知障碍患者103例(LACI组),脑白质疏松无认知障碍患者100例(对照组),观察中医四诊信息,通过因子分析方法,提取证候要素。结果因子分析结果得出LACI组15个公因子(证候要素)、对照组12个公因子,对各例患者证候要素分布情况进行分析,发现LACI组中阳虚占33.98%,痰占22.33%,阴虚占19.42%,气虚占10.68%,火占9.71%,血虚、血瘀占3.88%;对照组中阳虚占31.00%,气虚占27.00%,阴虚、火占24.00%,血虚、血瘀占12.00%,阳虚、痰、血虚占6.00%。结论 LACI的主要证候要素是阳虚、痰、阴虚、火,次要证候要素为气虚、血虚、血瘀。主要涉及肾、脾两脏,次要脏腑为肝、心,以虚为发病基础,痰、火等病理因素为其发展和加重的关键,复合证候要素多,病情复杂。