Sensory evoked potentials in patients with Rett syndrome through the lens of animal studies: Systematic review

ObjectiveSystematically review the abnormalities in event related potential (ERP) recorded in Rett Syndrome (RTT) patients and animals in search of translational biomarkers of deficits related to the particular neurophysiological processes of known genetic origin (MECP2 mutations).MethodsPubmed, ISI Web of Knowledge and BIORXIV were searched for the relevant articles according to PRISMA standards.ResultsERP components are generally delayed across all sensory modalities both in RTT patients and its animal model, while findings on ERPs amplitude strongly depend on stimulus properties and presentation rate. Studies on RTT animal models uncovered the abnormalities in the excitatory and inhibitory transmission as critical mechanisms underlying the ERPs changes, but showed that even similar ERP alterations in auditory and visual domains have a diverse neural basis. A range of novel approaches has been developed in animal studies bringing along the meaningful neurophysiological interpretation of ERP measures in RTT patients.ConclusionsWhile there is a clear evidence for sensory ERPs abnormalities in RTT, to further advance the field there is a need in a large-scale ERP studies with the functionally-relevant experimental paradigms.SignificanceThe review provides insights into domain-specific neural basis of the ERP abnormalities and promotes clinical application of the ERP measures as the non-invasive functional biomarkers of RTT pathophysiology.     

阿尔茨海默病患者脑白质损害与认知功能的关系

目的用磁共振扩散张量成像(DTI)研究阿尔茨海默病(AD)患者脑白质损害的特点及其与认知功能改变的相关性。方法对16例AD患者和12名年龄及性别相当的健康老年人行DTI、T1液体衰减反转恢复序列(FLAIR)及T2-FLAIR检查,测量胼胝体膝部和压部、内囊前肢和后肢、额颞顶枕叶白质的部分各向异性分数值(FA)和平均弥散度(MD),分析FA、MD值与简易精神状态量表(MMSE)评分之间的相关关系。结果AD患者胼胝体压部、额叶、顶叶、颞叶FA值分别为0.602±0.043、0.270±0.034、0.294±0.043、0.302±0.032,与健康老人组相比显著下降(P<0.05),且与MMSE评分呈正相关关系,而内囊前后肢、枕叶、胼胝体膝部的FA值则无明显变化(P>0.05);胼胝体压部、顶叶白质的MD值分别为(0.918±0.029)、(0.826±0.015)×10-9m2/s,与健康老人组相比显著升高(P<0.01),且与MMSE评分呈负相关,而内囊前后肢、额叶、颞叶、枕叶和胼胝体膝部的MD值则无明显变化(P>0.05)。结论AD患者表现为脑白质的选择性损害,且损害程度与认知功能密切相关;这种选择性损害反映了AD病理机制中皮质-皮质及皮质-皮质下联系的丢失;DTI技术可以用来监测疾病的进展情况及评价AD治疗药物的临床疗效。     

Structural white matter abnormalities in patients with idiopathic dystonia

We investigated whether structural white matter abnormalities, in the form of disruption of axonal coherence and integrity as measured with diffusion tensor imaging (DTI), constitute an underlying pathological mechanism of idiopathic dystonia (ID), independent of genotype status. We studied seven subjects with ID: all had cervical dystonia as their main symptom (one patient also had spasmodic dysphonia and two patients had concurrent generalized dystonia, both DYT1‐negative). We compared DTI MR images of patients with 10 controls, evaluating differences in mean diffusivity (MD) and fractional anisotropy (FA). ID was associated with increased FA values in the thalamus and adjacent white matter, and in the white matter underlying the middle frontal gyrus. ID was also associated with increase in MD in adjacent white matter to the pallidum and putamen bilaterally, left caudate, and in subcortical hemispheric regions, including the postcentral gyrus. Abnormal FA and MD in patients with ID indicate that abnormal axonal coherence and integrity contribute to the pathophysiology of dystonia. These findings suggest that ID is not only a functional disorder, but also associated with structural brain changes. Impaired connectivity and disrupted flow of information may contribute to the impairment of motor planning and regulation in dystonia. © 2006 Movement Disorder Society     

The effect of ionic strength on the kinetics of rigor development in skinned fast-twitch skeletal muscle fibres

 Recent atomic 3-D reconstructions of the acto-myosin interface suggest that electrostatic interactions are important in the initial phase of cross-bridge formation. Earlier biochemical studies had also given strong evidence for the ionic strength dependence of this step in the cross-bridge cycle. We have probed these interactions by altering the ionic strength (Γ/2) of the medium mainly with K⁺, imidazole⁺ and EGTA^2– to vary charge shielding. We examined the effect of ionic strength on the kinetics of rigor development at low Ca²⁺ (experimental temperature 18–22°C) in chemically skinned single fast-twitch fibres of mouse extensor digitorum longus (EDL) muscle. On average the delay before rigor onset was 10 times longer, the maximum rate of rigor tension development was 10 times slower, the steady-state rigor tension was 3 times lower and the in-phase stiffness was 2 times lower at high (230 mM) compared to low (60 mM) ionic strength. These results were modelled by calculating ATP depletion in the fibre due to diffusional loss of ATP and acto-myosin Mg.ATPase activity. The difference in delay before rigor onset at low and high ionic strength could be explained in our model by assuming a 15 times higher Mg.ATPase activity and a threefold increase in K _m in relaxing conditions at low ionic strength. Activation by Ca²⁺ induced at different time points before and during onset of rigor confirmed the calculated time course of ATP depletion. We have also investigated ionic strength effects on rigor development with the activated troponin/tropomyosin complex. ATP withdrawl at maximum activation by Ca²⁺ induced force transients which led into a ”high rigor” state. The peak forces of these force transients were very similar at low and high ionic strength. The subsequent decrease in tension was only 10% slower and steady-state ”high rigor” tension was reduced by only 27% at high compared to low ionic strength. Addition of 10 mM phosphate to lower cross-bridge attachment strongly suppressed the transient increases in force at high ionic strength and reduced the steady-state rigor tension by 17%. A qualitatively similar but smaller effect of phosphate was observed at low ionic strength where steady-state rigor force was reduced by 10%. The data presented in this study show a very strong effect of ionic strength on rigor development in relaxed fibres whereas the ionic strength dependence of rigor development after thin filament activation was much less. The data confirm the importance of electrostatic interactions in cross-bridge attachment and cross-bridge-attachment-induced activation of thin filaments. Received: 3 September 1997 / Received after revision and accepted: 12 December 1997     

Impact of Ultrafiltration on Back-Diffusion in Hemodialyzer

Abstract: Ultrafiltration of water from blood to dialysate decreases the rate of back–diffusion of solutes from dialysate to blood. Therefore, back–clearance ( bK ) of hemodialyzers may be expressed as bK = bK _o – bTrQ _u, where bK _o is the diffusive back–clearance, bTr is the "back–"transmittance coefficient, and Qu is the net ultrafiltration rate. A formula for bK was derived from the one–dimensional theory of hemodialyzer, and bTr was described as a function of bK _o and the Staverman reflection coefficient. The transport parameters, bK _o and bTr , for creatinine and vitamin B₁₂ were measured in two types of hemodialyzers with negligible back–filtration, using water solutions, and compared with the transport parameters, K _o and Tr , for the case of both diffusion and ultrafiltration from blood to dialysate. bK _o was in general equal to K_o. bTr was not different from Tr for creatinine whereas bTr was lower than Tr for vitamin B₁₂. Experimental values of bTr for vitamin B₁₂ were in general agreement with theoretical predictions. However, experimental values of bTr for creatinine were lower than predicted values. We conclude that the impact of ultrafiltration on back–clearance for slowly diffusing solutes is weaker than on their clearance.     

Diffusion-weighted magnetic resonance imaging for demonstration of cerebral infarcts

Summary Forty-one patients demonstrating clinical symptoms for cerebral infarction were investigated by magnetic resonance imaging with diffusion-weighted echo-planar imaging (DWI) and T2-weighted imaging (T2WI). In 8 patients only DWI showed the cerebral lesions clearly. One patient with positive DWI and T2WI suffered from HSV encephalitis. DWI is superior to T2WI in assessment of small cortical infarcts and cerebral infarction in patients with preexisting vascular lesions. DWI is not specific, so other causes like cerebral hematoma and encephalitis have to be considered.      

颅内表皮样囊肿的常规T_1WI、T_2WI、FLAIR及DWI对比分析

目的:通过定性分析和定量比较来探讨颅内表皮样囊肿(ECs)的FLAIR和DWI特征。方法:ECs16例,测量其T1WI、T2WI、FLAIR及DWI上病灶信号强度和ADC值,计算组织间对比度(CR)和对比噪声比(CNR)。结果:在FLAIR上ECs平均信号强度高于脑脊液(CSF),低于脑组织。在T1WI上,表皮样囊肿与脑脊液间的CR和CNR分别是0.11±0.06和1.02±1.11;在T2WI上,ECs与CSF间的CR和CNR分别是0.05±0.04和1.05±0.58;而在DWI上,ECs与CSF间的CR是12.56±2.87,CNR是18.23±5.42。16例患者示踪DWI图像上均呈明显高信号。ECs平均ADC值明显低于CSF(P<0.001),而高于脑白质(P=0.002)。结论:FLAIR对颅内表皮样囊肿显示优于常规MRI序列,DWI描述ECs轮廓优于其它MRI序列。     

MR扩散加权成像鉴别脑结核瘤及高级星形细胞瘤和脑转移瘤的价值

目的探讨MR扩散加权成像（DWI）在脑结核瘤、高级星形细胞瘤和脑转移瘤鉴别诊断中的价值。方法14例脑结核瘤、15例脑高级星形细胞瘤和21例脑转移瘤患者，在术前或接受治疗前行常规MRI和DWI。测量并计算3种疾病瘤体、瘤周围水肿带的平均表观扩散系数（ADC）值和病灶与对侧相应部位正常脑白质区ADC值的比值（rADC值）。结果脑结核瘤瘤体平均ADC值和rADC值分别为（1．2±0．2）×10^-3mm^2·s^-1和1．6±0．3，高级星形细胞瘤瘤体平均ADC值和rADC值分别为（0．8±0．1）×10^-3mm^2·s^-1和1．1±0．1，转移瘤瘤体平均ADC值和rADC值分别为（0．8±0．1）×10^-3mm^2·s^-1和1．0±0．2。3种疾病瘤体平均ADC值（F=33．57，P〈0．01）之间和rADC值（F=33．27，P〈0．01）之间差异均有统计学意义。脑结核瘤瘤周水肿带平均ADC值和rADC值分别为（1．8±0．1）×10^-3mm^2·s^-1和2．5±0．2，脑高级星形细胞瘤瘤周水肿带平均ADC值和rADC值分别为（1．4±0．2）×10^-3mm^2·s^-1和1．8±0．3，脑转移瘤瘤周水肿带平均ADC值和rADC值分别为（1．9±0．2）×10^-3mm^2·s^-1和2．3±0．5。3种疾病瘤周围水肿带平均ADC值（F=23．17，P〈0．01）之间和rADC值（F=5．94，P〈0．01）之间差异均有统计学意义。结论结合MRI、DWI检测方法，根据病灶瘤体和瘤周水肿带的ADC和rADC值可帮助鉴别脑结核瘤、脑高级星形细胞瘤和脑转移瘤。     

弥散张量磁共振成像方法概述

弥散张量成像(diffusion tensor imaging,DTI)是一种根据组织内水分子的弥散特性来探测有机体的微观结构和病理改变的核磁共振成像方法,目前已经成为临床评估和生命科学研究重要的工具。本文结合近年来的文献综述了弥散张量成像的基本原理,列举了目前常用的成像方法,分析了它们的优缺点以及用途,并对弥散张量成像的发展方向作了一些展望。