1H-MRS评估慢性肝病脑部代谢异常与肝硬化的相关性

目的:利用~1H-MRS研究慢性肝病脑部代谢改变,并探讨~1H-MRS评估慢性肝病脑部代谢异常与肝硬化Child-Pugh分级的相关性。方法:选取经临床确诊为慢性肝炎肝硬化患者42例(child A 19例,child B14例,child C 9例)及健康志愿者15例(对照组),行磁共振平扫及磁共振单体素~1H-MRS检查,计算相关代谢物N-乙酰天门冬氨酸(NAA)、谷氨酰胺复合物(Glx)、胆碱(Cho)、肌醇(mI)和肌酸(Cr)的峰下面积及前四项指标与Cr的比值(NAA/Cr、Glx/Cr、Cho/Cr、mI/Cr),并进行统计学分析,同时对相关代谢物的变化与肝硬化Child-Pugh分级及肝硬化Child-Pugh分级与肝性脑病的关系进行相关性分析。结果:~1HMRS分析显示与正常对照组相比,慢性肝炎肝硬化组Glx/Cr值升高,Cho/Cr与mI/Cr值降低,且差异均有统计学意义(P0.05);不同程度肝硬化病例组对比显示,Glx/Cr值均随着肝硬化程度加重而增大,且Glx/Cr值的差异在child A、child B、child C组中均有统计学意义(P0.05);肝性脑病(HE)组与非肝性脑病组脑代谢物峰下面积比值Glx/Cr、Cho/Cr、mI/Cr比较,差异有统计学意义(P0.05);Child-Pugh分级与Glx/Cr呈正相关,与Cho/Cr、mI/Cr呈负相关;随着肝硬化程度加重,肝性脑病出现概率越高,差异有统计学意义(P0.05)。结论:~1H-MRS作为一种无创性的评价手段,能够反映慢性肝硬化及肝性脑病患者存在脑代谢物浓度异常改变,可作为早期诊断肝硬化、肝性脑病及评价肝硬化、肝性脑病严重程度的一项指标,在一定程度上评估肝性脑病与肝硬化分级具有相关性。     

人参皂苷Rb1对Aβ_(1-42)导致的Tau蛋白异常磷酸化的影响

为探讨人参皂苷Rb1对Aβ_(1-42)所致小鼠脑片微管相关蛋白(Tau)异常磷酸化的抑制作用及其可能机制,采用Aβ_(1-42)诱导小鼠海马脑片建立Tau蛋白过度磷酸化模型,运用免疫印迹方法观察人参皂苷Rb1对Aβ1-42导致小鼠脑片p-Tau、p-Erk1/2、Erk1/2蛋白水平的影响。实验结果显示,模型组p-Tau、p-Erk1/2表达水平明显高于空白对照组(P0.01);与模型组比较,人参皂苷Rb1各剂量组p-Tau、p-Erk1/2表达水平显著性降低(P0.01或P0.05),且大、中剂量组优于小剂量组;人参皂苷Rb1呈一定的剂量依赖性下调Aβ_(1-42)导致的p-Tau、p-Erk1/2的蛋白水平。本研究表明,人参皂苷Rb1可能通过抑制Erk1/2的激活逆转Aβ_(1-42)所导致的Tau蛋白水平的升高来减少神经纤维缠结。     

脑出血患者脑脊液Abeta水平检测及其临床意义

目的:探讨脑出血患者脑脊液中amylid-beta(Aβ)40和Aβ42水平及其与出血量以及血肿周围低密体积相关性。方法:采集73例脑出血患者及72例健康对照的脑脊液标本,采用酶联免疫吸附法(Elisa)检测脑脊液中的Aβ40和Aβ42的水平,分析其与出血量和血肿周围低密度体积的相关性。结果:(1)脑出血患者脑脊液Aβ40和Aβ42水平显著高于健康对照组(P0.01)。(2)脑出血患者脑脊液Aβ40(r=0.549,P0.01;r=0.791,P0.01)和Aβ42(r=0.450,P0.01;r=0.440,P0.01)水平与出血量及血肿周围低密度体积呈正相关。结论:Aβ40和Aβ42水平为神经元损害的标志物,本研究提示脑脊液Aβ40和Aβ42水平对于判断脑出血严重程度具有临床参考价值。     

持续脑电双频指数监测在脓毒症相关性脑病患者中的应用价值

目的:探讨持续脑电双频指数监测(Bispectral Index,BIS)用于脓毒症相关性脑病患者诊断及病情评估的临床应用价值。方法:选择2015年1月-2018年6月我院重症加强治疗病房(Intensive Care Unit,ICU)收治的脓毒症患者90例,其中38例患者出现脓毒症相关性脑病(脑病组),其余52例患者为非脓毒症相关性脑病(非脑病组)。所有患者在入住ICU后进行BIS持续监测24 h,并比较两组患者的血清降钙素原(procalcitonin,PCT)、S100β水平,并分析BIS与格拉斯哥昏迷评分(glasgow coma scale,GCS)、APACHE-Ⅱ的相关性。结果:脑病组患者的血清PCT、S100β水平及急性生理健康与慢性疾病评分(Acute Physiology and Chronic Health EvaluationⅡscore,APACHE-II)均明显高于非脑病组(P0.05),而BIS值、GCS评分均明显低于非脑病组(P0.05)。脓毒症相关性脑病患者BIS值与GCS评分呈正显著相关性(r=0.487,P=0.013),与APACHE-II评分呈明显负相关性(r=-0.682,P=0.027)。结论:采用BIS监测脓毒症患者利于相关性脑病的及早诊断,结合检测血清PCT、S100β水平变化可能有助于判断患者的病情严重程度。     

婴儿肝炎综合征甲状腺素与Child-Pugh分级的关系

目的:肝脏是甲状腺激素降解、排泄及转化的场所,参与甲状腺结合球蛋白的合成.肝脏及肝脏疾病与甲状腺激素关系方面的文献很多,但有关婴儿肝炎综合征(infantile hepatitis syndrome,IHS)甲状腺素水平的报道很少.本文研究IHS患儿血清甲状腺素水平与Child-Pugh肝功能分级的关系,探讨甲状腺素水平对于指导肝功能的分级、评价肝脏储备功能及其预后的临床意义.方法:收集住院的IHS患儿38例,选择20例健康儿作为正常对照组.应用放射免疫法检测各组血清促甲状腺素(TSH)、游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)水平.检测IHS患儿血清白蛋白(ALB)、总胆红素(TBIL)、凝血酶原时间(PT),并记录腹水、肝性脑病等临床情况,按成人Child-Pugh分级标准,将患儿分为A、B、C三级,并将Child-Pugh积分与其甲状腺功能各指标做相关性分析.结果:1、IHS组患儿血清FT3、FT4水平显著低于正常对照组(P＜0.05),TSH水平高于正常对照组水平(P＜0.05);FT3、FT4水平随Child-Pugh积分增加而下降,A、B、C三级组间比较有显著性差异(P＜0.05);TSH水平在三级组间无统计学差异(P＞0.05).2、HIS患儿的血清FT3、FT4水平与Child-Pugh积分呈负相关(r=-0.619～-0.80,P＜0.01),与TSH无相关性(P＞0.05).结论:本研究结果显示婴儿肝炎综合征患儿的血清FT3、FT4水平降低,且与其肝脏受损程度有明显的相关性,因此检测血清FT3、FT4水平,对正确评估婴儿肝炎综合征病情严重程度及其预后具有重要的参考价值.     

NT-proBNP在慢性充血性心力衰竭中的表达及与NYHA分级和LVEF的关系

目的:探讨血浆氨基末端脑钠肽前体(NT-proBNP)在慢性充血性心力衰竭(CHF)中的表达及与心功能分级(NYHA)和左室射血分数(LVEF)的关系。方法:选择我院收治的100例CHF患者作为研究组,同时选择同期在我院体检的健康者100例作为对照组,分别检测两组NT-proBNP及LVEF,并对研究组患者NT-proBNP与NYHA分级和LVEF进行相关性分析。结果:研究组NT-proBNP水平明显高于对照组,LVEF水平明显低于对照组,差异均有统计学意义(t=9.82,7.63;P0.01)。研究组血浆NT-proBNP水平随着NYHA分级的升高而显著升高,同时LVEF水平随NYHA分级的升高而显著下降(P0.01)。研究组NT-proBNP水平与NYHA分级呈正相关性(r=0.812,P0.01),与LVEF呈明显负相关性(r=-0.623,P0.01)。结论:血浆NT-proBNP水平可早期反映出局部心脏结构改变造成的心功能变化,可与NYHA及LVEF联合检测作为临床诊断CHF的指标。     

血清胱抑素C 与乙型肝炎性肝硬化肝功能损害程度的相关性分析

目的:探讨血清胱抑素C(Cys C)与乙型肝炎性肝硬化患者肝功能损伤程度的相关性分析。方法:将98例乙型肝炎性肝硬化患者按照肝功能分级的Child-Pugh评分将分为A组(Child A级,n=45例)、B组(Child B级,n=33例)、C组(Child C级,n=20例),同期选取本院门诊正常健康体检者为对照组,检测所有受试者的血清Cys C水平,比较各种之间相关指标的差异。结果:A组、B组、C组、对照组丙氨酸氨基转移酶(ALT)、天门冬氨酸转移酶(AST)、血清白蛋白(ALB)、血清Cys C及血清Cys C阳性率均有统计学差异(P0.05),C组血清Cys C、血清Cys C阳性率高于对照组(P0.05)、A组、B组,而B组高于对照组、A组(P0.05);血清Cys C阳性组与阴性组中含有Child A级、Child B级、Child C级患者的构成比具有统计学意义(P0.05),Cys C阳性组中的Child C级患者比例高于阴性组(P0.05);血清Cys C与Child-Pugh评分呈正相关(P0.05);Child-Pugh评分、ALT、AST与患者血清Cys C阳性呈正相关(P0.05);而ALB则与其呈负相关(P0.05);结论:乙型肝炎性肝硬化患者血清Cys C水平与肝功能损伤程度呈一定相关性,早期检测血清Cys C水平对于评估乙型肝炎性肝硬化患者的肝功能损害具有一定的临床意义。     

新生儿缺氧缺血性脑病脑脊液和血浆IL-1β和TNF-α水平的检测及临床意义

目的:检测缺新生儿氧缺血性脑病(HIE)脑脊液和血浆白细胞介素1β(IL-1β)和肿瘤坏死因子α(TNF-α)水平,探讨IL-1β和TNF-α水平与HIE严重程度之间的关系.方法:采用ELISA法测定HIE组(28例)和对照组(13例)新生儿出生后24h内脑脊液和血浆IL-1β和TNF-α水平.结果:HIE组脑脊液和血浆IL-1β和TNF-α水平均明显高于对照组(p<0.01或者0.05),其脑脊液和血浆IL-1β水平比是4.05,TNF-α水平比是2.15.重度HIE组脑脊液IL-1β和TNF-α水平较轻和中度HIE组明显升高(p<0.01或者0.05).脑脊液IL-1β水平与HIE分度相关性(r=0.68,P<0.01)较脑脊液TNF-α水平与HIE分度相关性好(r=0.42,p<0.01).结论:新生儿缺氧缺血性脑病脑脊液和血浆IL-1β和TNF-α水平均升高.较高的脑脊液和血浆IL-1β水平比和TNF-α水平比暗示这些因子产生于缺氧缺血性脑病新生儿的受损脑组织.脑脊液IL-1β水平与HIE分度相关性较TNF-α水平好.     

PTVE 与TIPS治疗肝硬化门静脉高压合并食管胃底静脉曲张破裂出血 的疗效比较

目的:研究经皮胃底曲张静脉栓塞术(PTVE)和经颈静脉肝内门体分流术(TIPS)治疗肝硬化门静脉高压合并食管胃底静脉曲张破裂出血的临床疗效,为临床治疗提供依据。方法:选取2001年4月到2015年4月我院肝硬化门静脉高压合并食管胃底静脉曲张破裂患者169例,根据手术方式分为PTVE组(行PTVE治疗)141例和TIPS组(行TIPS治疗)28例,比较两组术前、术后门静脉压力,术前、术后3个月、6个月以及1年两组Child-Pugh评分、白蛋白以及直接胆红素,并比较两组再出血和肝性脑病发生率。结果:TIPS组术后门静脉压力较术前显著降低,比较差异具有统计学意义(P0.05),术后PTVE组及TIPS组组间比较差异具有统计学意义(P0.05);两组术前和术后各时间直接胆红素无统计学意义(P0.05);PTVE组术后1年白蛋白水平显著升高,与术前和TIPS组比较差异具有统计学意义(P0.05),TIPS组术后白蛋白有所升高,但各时间比较差异无统计学意义(P0.05),PTVE组术后各时间Child-Pugh评分较术前明显改善,比较差异具有统计学意义(P0.05),TIPS组术后3个月和术后6个月Child-Pugh评分较术前明显改善,比较差异具有统计学意义(P0.05);两组术后再出血发生率比较无统计学意义(P0.05),PTVE组肝性脑病发生率显著低于TIPS组,比较差异具有统计学意义(P0.05)。结论:PTVE和TIPS治疗肝硬化门静脉高压合并食管胃底静脉曲张破裂出血效果相当,TIPS能显著降低门静脉压,PTVE能降低肝性脑病的发生率,改善患者Child-Pugh评分。     

类风湿关节炎患者血脂水平与疾病活动度的相关性研究

目的:观察类风湿关节炎(RA)患者血脂的变化,以及血脂水平与疾病活动度之间的相关性。方法:对71例RA患者和77例正常对照的血脂水平进行回顾性分析,并对RA患者的血脂水平与其疾病活动度进行相关性分析。结果:RA患者的血清总胆固醇(TC)、甘油三酯(TG)水平均高于正常对照组(P0.01),高密度脂蛋白(HDL)水平降低(P0.01)。DAS28评分与TC(r=0.49,P0.01)、TG(r=0.38,P0.01)和LDL(r=0.55,P0.01)呈正相关,与HDL呈负相关(r=-0.57,P0.01),血沉与TC(r=0.26,P=0.03)、TG(r=0.28,P=0.02)呈正相关,C反应蛋白与TC(r=0.65,P0.01)、TG(r=0.30,P=0.01)和LDL(r=0.39,P0.01)均呈正相关。结论:RA患者存在血脂水平异常,且与疾病活动度相关。对血脂进行干预可能改善RA患者的长期预后。     

Cerebrospinal Fluid PKR Level Predicts Cognitive Decline in Alzheimer’s Disease

The cerebrospinal fluid (CSF) levels of the proapoptotic kinase R (PKR) and its phosphorylated PKR (pPKR) are increased in Alzheimer’s disease (AD), but whether CSF PKR concentrations are associated with cognitive decline in AD patients remain unknown. In this study, 41 consecutive patients with AD and 11 patients with amnestic mild cognitive impairment (aMCI) from our Memory Clinic were included. A lumbar puncture was performed during the following month of the clinical diagnosis and Mini-Mental State Examination (MMSE) evaluations were repeated every 6 months during a mean follow-up of 2 years. In AD patients, linear mixed models adjusted for age and sex were used to assess the cross-sectional and longitudinal associations between MMSE scores and baseline CSF levels of Aβ peptide (Aβ 1-42), Tau, phosphorylated Tau (p-Tau 181), PKR and pPKR. The mean (SD) MMSE at baseline was 20.5 (6.1) and MMSE scores declined over the follow-up (-0.12 point/month, standard error [SE] = 0.03). A lower MMSE at baseline was associated with lower levels of CSF Aβ 1–42 and p-Tau 181/Tau ratio. pPKR level was associated with longitudinal MMSE changes over the follow-up, higher pPKR levels being related with an exacerbated cognitive deterioration. Other CSF biomarkers were not associated with MMSE changes over time. In aMCI patients, mean CSF biomarker levels were not different in patients who converted to AD from those who did not convert.These results suggest that at the time of AD diagnosis, a higher level of CSF pPKR can predict a faster rate of cognitive decline.     

RNA Interference Silencing of Glycogen Synthase Kinase 3β Inhibites Tau Phosphorylation in Mice with Alzheimer Disease

To explore the effect of glycogen synthase kinase 3β (GSK-3β) silencing on Tau-5 phosphorylation in mice suffering Alzheimer disease (AD). GSK-3β was firstly silenced in human neuroblastoma SH-SY5Y cells using special lentivirus (LV) and the content of Tau (A-12), p-Tau (Ser396) and p-Tau (PHF-6) proteins. GSK-3β was also silenced in APP/PS1 mouse model of AD mice, which were divided into three groups (n = 10): AD, vehicle, and LV group. Ten C57 mice were used as control. The memory ability of mice was tested by square water maze, and the morphological changes of hippocampus and neuron death were analyzed by haematoxylin–eosin staining. Moreover, the levels of Tau and phosphorylated Tau (p-Tau) were detected by western blotting and immunohistochemistry, respectively. The lentivirus-mediated GSK-3β silencing system was successfully developed and silencing GSK-3β at the cellular level reduced Tau phosphorylation obviously. Moreover, GSK-3β silence significantly improved the memory ability of AD mice in LV group compared with AD group (P < 0.05) according to the latency periods and error numbers. As for the hippocampus morphology and neuron death, no significant change was observed between LV group and normal control. Immunohistochemical detection and western blotting revealed that the levels of Tau and p-Tau were significantly down-regulated after GSK-3β silence. Silencing GSK-3β may have a positive effect on inhibiting the pathologic progression of AD through down-regulating the level of p-Tau.

     

Label‐free analysis of human cerebrospinal fluid addressing various normalization strategies and revealing protein groups affected by multiple sclerosis

The aims of the study were to: (i) identify differentially regulated proteins in cerebrospinal fluid (CSF) between multiple sclerosis (MS) patients and non‐MS controls; (ii) examine the effect of matching the CSF samples on either total protein amount or volume, and compare four protein normalization strategies for CSF protein quantification. CSF from MS patients (n = 37) and controls (n = 64), consisting of other noninflammatory neurological diseases (n = 50) and non neurological spinal anesthetic subjects (n = 14), were analyzed using label‐free proteomics, quantifying almost 800 proteins. In total, 122 proteins were significantly regulated (p < 0.05), where 77 proteins had p‐value <0.01 or AUC value >0.75. Hierarchical clustering indicated that there were two main groups of MS patients, those with increased levels of inflammatory response proteins and decreased levels of proteins involved in neuronal tissue development (n = 30), and those with normal protein levels for both of these protein groups (n = 7). The main subgroup of controls clustering with the MS patients showing increased inflammation and decreased neuronal tissue development were patients suffering from chronic fatigue. Our data indicate that the preferable way to quantify proteins in CSF is to first match the samples on total protein amount and then normalize the data based on the median intensities, preferably from the CNS‐enriched proteins.     

Extracellular Tau Levels Are Influenced by Variability in Tau That Is Associated with Tauopathies

Tauopathies are a class of neurodegenerative diseases marked by intracellular aggregates of hyperphosphorylated Tau. These diseases may occur by sporadic mechanisms in which genetic variants represent risk factors for disease, as is the case in Alzheimer disease (AD). In AD, cerebrospinal fluid (CSF) levels of soluble Tau/pTau-181 are higher in cases compared with controls. A subset of frontotemporal dementia (FTD) cases occur by a familial mechanism in which MAPT, the gene that encodes Tau, mutations are dominantly inherited. In symptomatic FTD patients expressing a MAPT mutation, CSF Tau levels are slightly elevated but are significantly lower than in AD patients. We sought to model CSF Tau changes by measuring extracellular Tau in cultured cells. Full-length, monomeric extracellular total Tau and pTau-181 were detectable in human neuroblastoma cells expressing endogenous Tau, in human non-neuronal cells overexpressing wild-type Tau, and in mouse cortical neurons. Tau isoforms influence the rate of Tau release, whereby the N terminus (exons 2/3) and microtubule binding repeat length contribute to Tau release from the cell. Compared with cells overexpressing wild-type Tau, cells overexpressing FTD-associated MAPT mutations produce significantly less extracellular total Tau without altering intracellular total Tau levels. This study demonstrates that cells actively release Tau in the absence of disease or toxicity, and Tau release is modified by changes in the Tau protein that are associated with tauopathies.     

Tauopathic changes in the striatum of A53T α-synuclein mutant mouse model of Parkinson's disease

Tauopathic pathways lead to degenerative changes in Alzheimer's disease and there is evidence that they are also involved in the neurodegenerative pathology of Parkinson's disease [PD]. We have examined tauopathic changes in striatum of the α-synuclein (α-Syn) A53T mutant mouse. Elevated levels of α-Syn were observed in striatum of the adult A53T α-Syn mice. This was accompanied by increases in hyperphosphorylated Tau [p-Tau], phosphorylated at Ser202, Ser262 and Ser396/404, which are the same toxic sites also seen in Alzheimer's disease. There was an increase in active p-GSK-3β, hyperphosphorylated at Tyr216, a major and primary kinase known to phosphorylate Tau at multiple sites. The sites of hyperphosphorylation of Tau in the A53T mutant mice were similar to those seen in post-mortem striata from PD patients, attesting to their pathophysiological relevance. Increases in p-Tau were not due to alterations on protein phosphatases in either A53T mice or in human PD, suggesting lack of involvement of these proteins in tauopathy. Extraction of striata with Triton X-100 showed large increases in oligomeric forms of α-Syn suggesting that α-Syn had formed aggregates the mutant mice. In addition, increased levels of p-GSK-3β and pSer396/404 were also found associated with aggregated α-Syn. Differential solubilization to measure protein binding to cytoskeletal proteins demonstrated that p-Tau in the A53T mutant mouse were unbound to cytoskeletal proteins, consistent with dissociation of p-Tau from the microtubules upon hyperphosphorylation. Interestingly, α-Syn remained tightly bound to the cytoskeleton, while p-GSK-3β was seen in the cytoskeleton-free fractions. Immunohistochemical studies showed that α-Syn, pSer396/404 Tau and p-GSK-3β co-localized with one another and was aggregated and accumulated into large inclusion bodies, leading to cell death of Substantia nigral neurons. Together, these data demonstrate an elevated state of tauopathy in striata of the A53T α-Syn mutant mice, suggesting that tauopathy is a common feature of synucleinopathies.     

Brain-derived proteins in the CSF, do they correlate with brain pathology in CJD?

Background

Brain derived proteins such as 14-3-3, neuron-specific enolase (NSE), S 100b, tau, phosphorylated tau and Aβ_1–42 were found to be altered in the cerebrospinal fluid (CSF) in Creutzfeldt-Jakob disease (CJD) patients. The pathogenic mechanisms leading to these abnormalities are not known, but a relation to rapid neuronal damage is assumed. No systematic analysis on brain-derived proteins in the CSF and neuropathological lesion profiles has been performed.

Methods

CSF protein levels of brain-derived proteins and the degree of spongiform changes, neuronal loss and gliosis in various brain areas were analyzed in 57 CJD patients.

Results

We observed three different patterns of CSF alteration associated with the degree of cortical and subcortical changes. NSE levels increased with lesion severity of subcortical areas. Tau and 14-3-3 levels increased with minor pathological changes, a negative correlation was observed with severity of cortical lesions. Levels of the physiological form of the prion protein (PrP^c) and Aβ_1–42 levels correlated negatively with cortical pathology, most clearly with temporal and occipital lesions.

Conclusion

Our results indicate that the alteration of levels of brain-derived proteins in the CSF does not only reflect the degree of neuronal damage, but it is also modified by the localization on the brain pathology. Brain specific lesion patterns have to be considered when analyzing CSF neuronal proteins.     

Prion protein in exosomes: partnering Aβ peptides and driving fibrilization

Alterations of the cerebrospinal fluid (CSF) composition are useful clinical diagnostic tools as well as a source of candidates for new biomarkers of neurodegenerative disorders. This Editorial highlights a study by Rodrigues and colleagues in which the authors try to establish Tau as a new biomarker for Huntington´s disease (HD). The study confirmed in two independent, age‐controlled patient populations at various disease stages, asymptomatic mutation carriers and healthy controls, that CSF total Tau concentrations in HD gene mutation carriers are increased compared with healthy controls. This is a strong evidence that CSF total Tau concentration is associated with phenotypic variability in HD. Read the highlighted article ‘Cerebrospinal fluid total tau concentration predicts clinical phenotype in Huntington's disease’ on page 22 .     

Ubiquitin Carboxy-Terminal Hydrolase L1 (UCH-L1) is increased in cerebrospinal fluid and plasma of patients after epileptic seizure

ABSTRACT: BACKGROUND: Clinical and experimental studies have demonstrated that seizures can cause molecular and cellular responses resulting in neuronal damage. At present, there are no valid tests for assessing organic damage to the brain associated with seizure. The aim of this study was to investigate cerebrospinal fluid (CSF) and plasma concentrations of Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), a sensitive indicator of acute injury to brain neurons, in patients with tonic--clonic or partial secondarily generalized seizures due to various etiologies. METHODS: CSF and plasma concentrations of UCH-L1 were assessed in 52 patients within 48 hours after epileptic seizure and in 19 controls using ELISA assays. RESULTS: CSF obtained within 48 hours after seizure or status epilepticus (SE) presented significantly higher levels of UCH-L1 compared to controls (p = 0.008). Plasma UCH-L1 concentrations were negatively correlated with time to sample withdrawal. An analysis conducted using only the first 12 hours post-seizure revealed significant differences between concentrations of UCH-L1 in plasma and controls (p = 0.025). CSF and plasma concentrations were strongly correlated with age in patients with seizure, but not in control patients. Plasma UCH-L1 levels were also significantly higher in patients after recurrent seizures (n = 4) than in those after one or two seizures (p = 0.013 and p = 0.024, respectively). CONCLUSION: Our results suggest that determining levels of neuronal proteins may provide valuable information on the assessment of brain damage following seizure. These data might allow clinicians to make more accurate therapeutic decisions, to identify patients at risk of progression and, ultimately, to provide new opportunities for monitoring therapy and targeted therapeutic interventions.     

Amyloid beta peptide ratio 42/40 but not A beta 42 correlates with phospho-Tau in patients with low- and high-CSF A beta 40 load

Neurochemical dementia diagnostics (NDD) can significantly improve the clinically based categorization of patients with early dementia disorders, and the cerebrospinal fluid (CSF) concentrations of amyloid beta peptides ending at the amino acid position of 42 (A beta x-42 and A beta 1-42) are widely accepted biomarkers of Alzheimer's disease (AD). However, in subjects with constitutively high- or low-CSF concentrations of total A beta peptides (tA beta), the NDD interpretation might lead to erroneous conclusions as these biomarkers seem to correlate better with the total A beta load than with the pathological status of a given patient in such cases. In this multicenter study, we found significantly increased CSF concentrations of phosphorylated Tau (pTau181) and total Tau in the group of subjects with high CSF A beta x-40 concentrations and decreased A beta x-42/x-40 concentration ratio compared with the group of subjects with low CSF A beta x-40 and normal A beta ratio (p<0.001 in both cases). Furthermore, we observed significantly decreased A beta ratio (p<0.01) in the group of subjects with APOE epsilon 4 allele compared with the group of subjects without this allele. Surprisingly, patients with low-A beta x-40 and the decreased A beta ratio characterized with decreased pTau181 (p<0.05), and unaltered total Tau compared with the subjects with high A beta x-40 and the A beta ratio in the normal range. We conclude that the amyloid beta concentration ratio should replace the 'raw' concentrations of corresponding A beta peptides to improve reliability of the neurochemical dementia diagnosis.