脑白质疏松症弥散张量成像的探讨

脑白质疏松症发病率逐渐增高,其相关的神经功能障碍严重影响生活质量,因此早期发现LA患者存在的隐匿性损伤对早期治疗及预防有重要临床意义。LA的病理生理学特点为血管内皮细胞的受损引起血管通透性的改变,从而使周围组织的弥散程度发生改变,细胞外水分子运动对信号的改变起主导作用。DTI是目前检测脑白质唯一的无创性方法,可从量和方向上反映成像的体素内水分子扩散的变化,可以测量组织中扩散的各向异性。DTI较传统的MR能更好的反应神经系统白质的超微结构的改变,为影像学与其病理生理的相关性研究提供新的方法。目前对脑白质疏松的研究主要集中在与神经功能相关区域DTI量化指标的改变,因此本文对脑白质疏松的DTI技术的应用及发展趋势进行综述。     

血清UA、CysC、Lp-PLA2与急性脑梗死合并脑白质疏松症患者预后的关系研究

摘要 目的：探讨血清尿酸（UA）、胱抑素C（CysC）、脂蛋白相关磷脂酶 A2（Lp-PLA2）水平与急性脑梗死合并脑白质疏松症患者预后的关系。方法：选择2020年3月至2022年12月中国人民解放军联勤保障部队第九六0医院收治的113例急性脑梗死合并脑白质疏松症患者,检测血清UA、CysC、Lp-PLA2水平。随访1个月,根据改良Rankin量表（mRS）评分将患者分为预后良好组（0～2分,75例）和预后不良组（3分及以上,38例）。多因素Logistic回归分析急性脑梗死合并脑白质疏松症患者预后不良的危险因素,受试者工作特征曲线（ROC）分析血清UA、CysC、Lp-PLA2对急性脑梗死合并脑白质疏松症患者预后不良的预测价值。结果：预后不良组血清UA、CysC、Lp-PLA2水平高于预后良好组（P＜0.05）。多因素Logistic回归分析显示重度脑白质病变、高入院时NIHSS评分,高血清UA、CysC、Lp-PLA2水平是急性脑梗死合并脑白质疏松症患者预后不良的危险因素（P＜0.05）。联合血清UA、CysC、Lp-PLA2预测急性脑梗死合并脑白质疏松症患者预后的曲线下面积（AUC）为0.916,高于单独预测。结论：急性脑梗死合并脑白质疏松症患者血清UA、CysC、Lp-PLA2水平增高且与预后不良有关,联合血清UA、CysC、Lp-PLA2预测急性脑梗死合并脑白质疏松症患者预后不良价值较高。     

急性脑梗死合并脑白质疏松症患者血清CP、MBP、MCP-1与病情严重程度和预后的关系

摘要 目的：探究急性脑梗死（ACI）合并脑白质疏松症（LA）患者血清C肽（CP）、髓鞘碱性蛋白（MBP）、单核细胞趋化蛋白-1（MCP-1）水平与病情严重程度和预后关系。方法：选取南京鼓楼医院集团宿迁医院于2021年3月至2023年3月期间收治的ACI合并LA患者117例作为观察组,根据根据LA严重程度分为重度组39例、中度组40例和轻度组38例。另选取同期体检健康人120例纳入对照组。检测血清CP、MBP、MCP-1水平。对ACI合并LA患者行6个月的随访。多因素Logistic回归分析ACI合并LA患者预后不良的影响因素。受试者特征曲线（ROC）分析血清CP、MBP和MCP-1对ACI合并LA患者预后的预测价值。结果：与对照组相比,观察组MBP、MCP-1更高,CP更低（P<0.05）。重度组血清CP显著低于轻度组和中度组,MBP、MCP-1水平显著高于轻度组和中度组;中度组血清CP显著低于轻度组,MBP、MCP-1水平显著高于轻度组（均P<0.05）。与预后良好组相比,预后不良组CP更低,MBP、MCP-1更高（P<0.05）。多因素Logistic回归分析显示NIHSS评分升高、MBP升高、MCP-1升高是ACI合并LA患者预后不良的独立危险因素,CP升高是保护因素（P<0.05）。ROC分析结果显示CP、MBP和MCP-1联合预测ACI合并LA患者预后不良的曲线下面积（AUC）为0.916,高于CP、MBP和MCP-1单独预测。结论：ACI合并LA患者血清CP较健康群体更低,血清MBP、MCP-1水平较健康群体更高,且CP、MBP和MCP-1与患者病情程度存在密切联系。血清CP、MBP和MCP-1联合检测对ACI合并LA患者预后有较高预测价值。     

艾地苯醌联合石杉碱甲治疗脑梗死合并脑白质疏松认知功能障碍的疗效观察

目的观察艾地苯醌联合石杉碱甲治疗脑梗死合并脑白质疏松症认知功能障碍的疗效。方法将我院收治的58例脑梗死合并脑白质疏松症患者随机分为治疗组和对照组各29例,对照组在脑梗死的常规治疗上加用口服石杉碱甲100μg,每天2次,疗程1个月;治疗组在对照组的基础上加用艾地苯醌30mg,每天3次,连续1个月。观察比较两组疗效及治疗前后MMSE量表评分变化情况。结果治疗1个月后,两组患者的疗效及MMSE量表评分均优于治疗前,差异均有统计学意义(均P0.05);而且治疗组的疗效优于对照组,差异亦有统计学意义(P0.05)。结论艾地苯醌联合石杉碱甲治疗脑梗死合并脑白质疏松症认知功能障碍的疗效优于石杉碱甲单独给药的对照组,具有增效作用。     

产后与非产后抑郁症患者事件相关电位P300的对比研究

目的:探讨产后抑郁症与非产后抑郁症患者事件相关电位P300的差异,为产后抑郁症的预防提供参考指标。方法:选择2011年1月~2012年10月解放军第三医院精神科收治的35例产后抑郁症患者(产后组)和36例非产后抑郁症患者(非产后组)为研究对象,并检测其事件相关电位P300,并与36名健康志愿者(对照组)的结果进行比较。结果:(1)与对照组相比,产后组、非产后组P2、N2、P3潜伏期均显著延迟,P2、N2、P3波幅均明显降低,差异均有统计学意义(P0.05)。(2)与产后组相比,非产后组P2、N2、P3潜伏期差异均无统计学意义(P0.05)。P2、N2波幅均偏高,差异均有统计学意义(P2[(5.0±2.1)ms vs.(3.9±1.8)μV],N2[(3.2±1.7)μV vs.(2.1±1.0)μV],P0.05),P3波幅差异无统计学意义(P0.05)。结论:产后与非产后抑郁症患者认知功能均受损,非产后抑郁患者受损程度大于产后抑郁患者;产后抑郁的外界感知能力和早期注意受损程度大于非产后抑郁患者。     

用P300评价连续工作记忆能力差异的研究

目的：评价长时间连续工作记忆的行为学表现与事件相关电位（Event-related potential,ERP）的关系。方法：对16位健康男性青年（平均年龄21.4岁）,连续进行1h的3-back数字倒背实验,记录ERP。结果：受试者的行为学表现明显差异,记录的ERP的P300波幅存在显著性差异（P〈0.01）。结论：ERP的P300成分可以客观评价行为学上的差异。     

"新异刺激"模型和P300

事件相关电位中的P30 0成分反映了大脑的基本认知功能 ,并且在科学研究和临床中得到了广泛应用。P30 0成分通常由“新异刺激 (oddball)”模型引出。本文主要介绍了新异刺激模型 ,以及该模型在视觉、听觉和痛觉刺激模式中的应用     

脑梗死患者的脑白质病变危险因素分析

目的：探索脑梗死患者中脑白质病变的危险因素。方法：以2012 年1 月至2014 年12 月我院神经内科收治的837 例脑梗死 患者为研究对象,采用Fazekas量表评价核磁共振T2WI脑室旁白质和皮质下白质病变严重程度。分别比较不同程度脑室旁白质 病变、皮质下白质病变患者间各个危险因素的差异,采用Logistic 回归分析脑白质病变的危险因素。结果：年龄、高血压是脑室旁 白质（OR 年龄=1.090,95%CI:0.073-0.099,P＜0.05;OR 高血压=1.699,95%CI:0.242-0.818,P＜0.05）和皮质下白质病变（OR 年龄 =1.074,95%CI:0.059-0.083,P＜0.05;OR高血压=1.353,95%CI:0.017-0.588,P＜0.05）共同的危险因素。收缩压（OR=1.008,95%CI: 0.001-0.015,P＜0.05）是皮质下白质病变的危险因素。结论：在脑梗死患者中,年龄、高血压是脑室旁白质病变、皮质下白质病变共 同的危险因素,收缩压是皮质下白质病变的危险因素。     

琥珀酸索利那新对女性膀胱活跃症患者P2X3受体表达的影响

目的:探讨琥珀酸索利那新对女性膀胱活跃症患者的治疗效果及对膀胱内P2X3受体的表达的影响。方法:选取我院收治的女性膀胱活跃症患者76例,随机分为两组,对照组38例,予托特罗定2 mg,早晚日2次口服;实验组38例,予琥珀酸索利那新5mg,日1次口服,2周为1个疗程,治疗2个疗程。比较两组患者的24 h排尿次数和尿急次数情况,初始尿意容量、最大尿流率、最大膀胱压容量的变化,以及膀胱内P2X3受体的表达情况。结果:治疗前两组患者尿急次数、排尿次数、尿意容量、最大尿流率及最大膀胱压容量无统计学差异,P0.05;治疗后,患者尿急次数及排尿次数降低,尿意容量、最大尿流率、最大膀胱压容量升高,与对照组比较,实验组改善更明显,差异具有统计学意义,P0.05。P2X3受体主要表达于膀胱黏膜层和黏膜下层,染色为棕黄色或金黄色;实验组P2X3表达低于正常组,差异具有统计学意义,P0.05。结论:琥珀酸索利那新能够缓解女性膀胱活跃症患者临床症状,其治疗机制可能为抑制了P2X3受体的表达。     

噪声暴露对大鼠事件相关电位P300的影响及其海马水平的机制

目的：研究噪声暴露对大鼠事件相关电位（ERP）的影响及海马水平的机制。方法：雄性SD大鼠,随机均分为正常对照组（C组）、噪声暴露组（N组）。暴露条件：105dB白噪声2．5h／d×20d。观察试验过程中第0、7、14和20d ERP各波的峰潜伏期以及峰峰幅度值,并检测海马神经元尼氏体、NMDAR2B及胞内钙浓度的变化。结果：在实验第14d、第20d,噪声暴露组动物ERP P3a、P3和P3b的峰潜伏期显著增长,而且在噪声暴露20d后,大鼠海马齿状回以及CA1区尼氏体显著减少（P〈0．01）,齿状回、CA1及CA3区NMDAB2B的免疫反应强度显著降低（P〈0．01）,神经元胞内钙浓度显著升高（P〈0．01）。结论：噪声暴露可致事件相关电位的改变,这可能与其海马神经元尼氏体、NMDAR2B以及胞内钙的变化有关。     

Defective translation initiation causes vanishing of cerebral white matter

Leukoencephalopathy with vanishing white matter (VWM) is one of the most prevalent inherited white-matter disorders, especially in Caucasian populations. VWM is unusual because of its sensitivity to febrile infections and minor head trauma. The basic defect of this enigmatic brain disease resides in the regulation of initiation of protein synthesis. Recently, undue activation of the unfolded-protein response has emerged as an important factor in the pathophysiology of VWM. Here, we discuss the mechanisms that might be responsible for the selective involvement of the brain white matter in VWM. At present, VWM research is in need of an animal model to study disease mechanisms and therapeutic interventions.     

P300 values in patients diagnosed with primary Sjogren syndrome

Purpose: Primary Sjogren syndrome (PSS) is an autoimmune disease characterized by symptoms of a dry mouth and eyes, in which other organs and systems are widely involved. Central nervous system (CNS) involvement in PSS is reported in a wide range between 2.5–60%. The reason is that the clinical picture can remain asymptomatic despite the presence of CNS involvement in the disease process. In this study, our aim was to evaluate subclinical cognitive impairment in patients with PSS by investigating P300 potential parameters.

Method: Forty-three female patients with PSS (mean age: 52.6?±?11.4 years) and 35 healthy female controls (mean age: 54.5?±?8.09 years) were included in the study. Mini-Mental State evaluations (MMSE) and brain MRI were performed in the patient and control groups. An event-related evoked potentials test (P300) was applied to those with normal MMSE.

Results: The P300 latencies of patients with PSS were significantly longer compared with the control group (p?=?.019). In patients with PSS, there was no difference in P300 parameters between ANA, Anti-SSA, Anti-SSB-positive and negative patients, and patients with or without sedimentation and CRP elevation. In addition, brain MRI revealed no statistically significant difference between patients with PSS with and without ischemic gliotic lesions (p=.48).

Conclusion: In our study, P300 latency was also found to be significantly longer in patients who had no white matter change. We believe that prolonged P300 potential latencies without associated white matter lesions in brain imaging may be associated with subclinical CNS involvement.     

Clock genes associate with white matter integrity in depressed bipolar patients

Human genetic studies have implicated specific genes that constitute the molecular clock in the manifestation of bipolar disorder (BD). Among the clock genes involved in the control system of circadian rhythms, CLOCK 3111 T/C and Period3 (PER3) influence core psychopathological features of mood disorders, such as patterns of sleep, rest, and activity, diurnal preference, cognitive performances after sleep loss, age at the onset of the illness, and response to antidepressant treatment. Furthermore, several studies pointed out that bipolar symptomatology is associated with dysfunctions in white matter (WM) integrity, suggesting these structural alterations as a possible biomarker of the disorder. We hypothesise that CLOCK and PER3 polymorphisms could be potential factors affecting WM microstructure integrity in bipolar patients. The relationship between these clock genes and DTI measures of WM integrity in a sample of 140 (53 M; 87 F) patients affected by BD type I was studied. Tract-based spatial statistics analyses on DTI measures of WM integrity were performed for each clock gene polymorphism, between the genetic groups. We accounted for the effect of nuisance covariates known to influence WM microstructure: age, sex, lithium treatment, age at the onset of the illness, and the number of illness episodes. We found that compared to T homozygotes, CLOCK C carriers showed a widespread increase of the mean diffusivity in several WM tracts. Compared with PER3^5/5 homozygotes, PER3^4/4 homozygotes showed significantly increased radial diffusivity and reduced fractional anisotropy in several brain WM tracts. No significant difference was observed between heterozygotes and the other subgroups. Altogether, this pattern of results suggests WM disruption in CLOCK C carrier and in PER3⁴ homozygotes. Sleep promotes myelination and oligodendrocyte precursor cell proliferation and associates with higher expression of genes coding for phospholipid synthesis and myelination in oligodendrocytes. These clock genes play a pivotal role in maintaining circadian rhythms and the sleep-wake cycle. Thus, it may be suggested that CLOCK rs1801260*C and PER3^4/4 influence myelination processes by regulating sleep quality and quantity.     

Antidepressant treatment normalizes white matter volume in patients with major depression

Objective

To investigate white matter volume abnormalities in patients with major depression and the effects of antidepressant treatment on white matter volume.

Method

Magnetic resonance imaging (MRI) was performed on 32 treatment-naïve depressed patients, 17 recovered patients who had received antidepressant treatment and subsequently achieved clinical recovery and 34 matched controls.

Results

Relative to the healthy controls, the treatment-naïve depressed patients showed increased white matter volumes in the left dorsolateral prefrontal cortex (DLPFC) and left putamen and reduced white matter volumes in the left cerebellum posterior lobe and left inferior parietal lobule. For the treatment-naïve patients, the length in months of the current depressive episode was positively correlated with the white matter volumes in both the left DLPFC and left putamen. In the recovered patients, the differences in white matter volume were no longer statistically significant relative to healthy controls. No significant difference was found in the total white matter volume among the three groups.

Conclusions

This study demonstrates that there were alterations in the white matter volumes of depressed patients, which might disrupt the neural circuits that are involved in emotional and cognitive function and thus contribute to the pathophysiology of depression. The finding of the significant correlations between refractoriness and the white matter volumes in the left DLPFC and left putamen combined with the finding that antidepressant treatment normalized the white matter volume of recovered patients, suggests that a quantitative, structural MRI measurement could act as a potential biomarker in depression therapy for individual subjects.     

Lipid composition of human cerebral white matter and myelin in phenylketonuria

Abstract— White matter and purified myelin from cerebral tissue obtained at autopsy from four phenylketonuric and five non-phenylketonuric mentally-retarded patients were analysed for lipids, DNA and protein. The lipid composition of the white matter and myelin was compared with that of a representative non-myelin component of white matter, the crude mitochondrial fraction. The total lipid content was significantly lower and the ratio of cholesterol to galactolipid was significantly higher in the white matter from the PKU patients than in that from the non-PKU patients. The lipid compositions of the myelin and ‘mitochondrial’ fraction, although differing from each other, did not exhibit appreciable differences between the PKU and non-PKU brain samples. However, the amount of myelin recovered from the brains of the PKU patients was, on the average, 40 percent lower than that recovered from non-PKU brains. The abnormal cholesterol: galactolipid ratio of PKU white matter could be accounted for by the altered proportion of myelin to non-myelin lipid components. The finding in PKU brains of a normal composition of lipids in the purified myelin and the absence of cholesterol esters in the white matter suggest that the deficiency in myelin may reflect an early arrest of myelination.     

Diffusion tensor imaging of cerebral white matter integrity in cognitive aging

In this article we review recent research on diffusion tensor imaging (DTI) of white matter (WM) integrity and the implications for age-related differences in cognition. Neurobiological mechanisms defined from DTI analyses suggest that a primary dimension of age-related decline in WM is a decline in the structural integrity of myelin, particularly in brain regions that myelinate later developmentally. Research integrating behavioral measures with DTI indicates that WM integrity supports the communication among cortical networks, particularly those involving executive function, perceptual speed, and memory (i.e., fluid cognition). In the absence of significant disease, age shares a substantial portion of the variance associated with the relation between WM integrity and fluid cognition. Current data are consistent with one model in which age-related decline in WM integrity contributes to a decreased efficiency of communication among networks for fluid cognitive abilities. Neurocognitive disorders for which older adults are at risk, such as depression, further modulate the relation between WM and cognition, in ways that are not as yet entirely clear. Developments in DTI technology are providing a new insight into both the neurobiological mechanisms of aging WM and the potential contribution of DTI to understanding functional measures of brain activity. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.     

Sex-dependent influences of obesity on cerebral white matter investigated by diffusion-tensor imaging

Several studies have shown that obesity is associated with changes in human brain function and structure. Since women are more susceptible to obesity than men, it seems plausible that neural correlates may also be different. However, this has not been demonstrated so far. To address this issue, we systematically investigated the brain''s white matter (WM) structure in 23 lean to obese women (mean age 25.5 y, std 5.1 y; mean body mass index (BMI) 29.5 kg/m², std 7.3 kg/m²) and 26 lean to obese men (mean age 27.1 y, std 5.0 y; mean BMI 28.8 kg/m², std 6.8 kg/m²) with diffusion-weighted magnetic resonance imaging (MRI). There was no significant age (p>0.2) or BMI (p>0.7) difference between female and male participants. Using tract-based spatial statistics, we correlated several diffusion parameters including the apparent diffusion coefficient, fractional anisotropy (FA), as well as axial (λ_∥) and radial diffusivity (λ_⊥) with BMI and serum leptin levels. In female and male subjects, the putative axon marker λ_∥ was consistently reduced throughout the corpus callosum, particularly in the splenium (r = −0.62, p<0.005). This suggests that obesity may be associated with axonal degeneration. Only in women, the putative myelin marker λ_⊥ significantly increased with increasing BMI (r = 0.57, p<0.005) and serum leptin levels (r = 0.62, p<0.005) predominantly in the genu of the corpus callosum, suggesting additional myelin degeneration. Comparable structural changes were reported for the aging brain, which may point to accelerated aging of WM structure in obese subjects. In conclusion, we demonstrate structural WM changes related to an elevated body weight, but with differences between men and women. Future studies on obesity-related functional and structural brain changes should therefore account for sex-related differences.