关键词： Neurological examination   Medical education   Incidental findings  

关键词： neurocritical care   pediatric   predictive modeling   prognostic modeling   traumatic brain injury  

摘要： Predictive modeling is foundational to treatment and long-term management of children with traumatic brain injury (TBI). Assessment of injury severity in the acute-care setting enables early stratification of patients based on their risk of death, lifelong disability, or unfavorable outcome. This review evaluates predictive models that have been developed or validated for pediatric TBI patients. The predictive accuracy of these models, the outcomes and time points predicted, and the variables and statistical methods utilized in model development were compared. Embase, Scopus, MEDLINE(R), and Web of Science were searched for studies that developed statistical models for predicting patient outcomes following pediatric TBI. Studies were excluded if they focused on adults or non-traumatic brain injury, or if they did not assess classification accuracy. A total of 4538 entries were identified and screened, with 7 studies included for analysis. This included five studies in which adult predictive models were validated for use in the pediatric setting, and two in which new models were derived from a pediatric cohort. Trials of adult prediction tools in pediatric cohorts, including the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) and Corticoid Randomisation After Significant Head Injury (CRASH)-TBI models, showed comparable accuracy between classification of adults and children. Models derived from pediatric cohorts showed improved accuracy. Most studies solely focused on clinical variables, with two studies incorporating biochemical and imaging variables. Predictive models for pediatric TBI are primarily based on methods and variables identified in adult studies. Although adult models have proven effective in select pediatric cohorts, they may be suboptimal when compared with models derived or adjusted for children.

关键词： Glutamate receptors   Channelopathy   Endogenous neurosteroid   Translational study   Rescue pharmacology  

摘要： N-methyl-D-aspartate receptors (NMDARs) mediate a slow component of excitatory synaptic transmission that plays important roles in normal brain function and development. A large number of disease-associated variants in the GRIN gene family encoding NMDAR GluN subunits have been identified in patients with various neurological and neuropsychiatric disorders. Many of these variants reduce the function of NMDARs by a range of different mechanisms, including reduced glutamate potency, reduced glycine potency, accelerated deactivation time course, decreased surface expression, and/or reduced open probability. We have evaluated whether three positive allosteric modulators of NMDAR receptor function (24(S)-hydroxycholesterol, pregnenolone sulfate, tobramycin) and three co-agonists (D-serine, L-serine, and D-cycloserine) can mitigate the diminished function of NMDARs harboring GRIN variants. We examined the effects of these modulators on NMDARs that contained 21 different loss-of-function variants in GRIN1 GRIN2A, or GRIN2B, identified in patients with epilepsy, intellectual disability, autism, and/or movement disorders. For all variants, some aspect of the reduced function was partially restored. Moreover, some variants showed enhanced sensitivity to positive allosteric modulators compared to wild type receptors. These results raise the possibility that enhancement of NMDAR function by positive allosteric modulators may be a useful therapeutic strategy.

关键词： maternally expressed gene 3   microRNA-378   growth factor receptor-bound protein 2 (GRB2)   Akt   mTOR signaling pathway   neuronal autophagy   neurological functional impairment   ischemic stroke   stroke   ischemia   neurological disease   autophagy  

摘要： Autophagy has been shown to maintain neural system homeostasis during stroke. However, the molecular mechanisms underlying neuronal autophagy in ischemic stroke remain poorly understood. This study aims to investigate the regulatory mechanisms of the pathway consisting of MEG3 (maternally expressed gene 3), microRNA-378 (miR-378), and GRB2 (growth factor receptor-bound protein 2) in neuronal autophagy and neurological functional impairment in ischemic stroke. A mouse model of the middle cerebral artery occluded-induced ischemic stroke and anin vitromodel of oxygen-glucose deprivation-induced neuronal injury were developed. To understand the role of the MEG3/miR-378/GRB2 axis in the neuronal regulation, the expression of proteins associated with autophagy in neurons was measured by Western blotting analysis, and neuron death was evaluated using a lactate dehydrogenase leakage rate test. First, it was found that the GRB2 gene, up-regulated in middle cerebral artery occluded-operated mice and oxygen-glucose deprivation-exposed neurons, was a target gene of miR-378. Next, miR-378 inhibited neuronal loss and neurological functional impairment in mice, as well as neuronal autophagy and neuronal death by silencing of GRB2. Confirmatoryin vitroexperiments showed that MEG3 could specifically bind to miR-378 and subsequently up-regulate the expression of GRB2, which in turn suppressed the activation of Akt/mTOR pathway. Taken together, these findings suggested that miR-378 might protect against neuronal autophagy and neurological functional impairment and proposed that a MEG3/miR-378/GRB2 regulatory axis contributed to better understanding of the pathophysiology of ischemic stroke.

关键词： G-quadruplexes   Neurological diseases   ATR-X syndrome   Porphyrins   5-aminolevulinic acid  

摘要： Genomic regions with guanine (G)-rich sequences make non-Watson-Crick base pairs, which result in the formation of unique nucleic acid structures called G-quadruplexes (G4s) in cells. Studies have suggested that abnormal G4s are involved in neurological diseases. For example, the formation of G4s caused by expansion of G-rich sequences is implicated in C9orf72-mediated amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD), and fragile X-related tremor/ataxia syndrome (FXTAS). In addition, the disruption and/or mutation of G4 binding proteins (G4BPs), such as heterogeneous nuclear ribonucleoproteins (hnRNPs) and DNA/RNA helicases, is related to neurological diseases. For instance, mutations in a G4BP called ATRX lead to a neurodevelopmental disorder, ATR-X syndrome, which is associated with intellectual disability. We found that porphyrins are potential candidate drugs for treating ATR-X syndrome through their G4 binding ability. Importantly, intracellular porphyrins are produced from 5-aminolevulinic acid (5-ALA) in vivo. Oral administration of 5-ALA improved cognitive dysfunction in an ATR-X syndrome model mouse, and language ability in an ATR-X syndrome patient. In this review, we suggest a novel therapeutic strategy targeting G4s using porphyrins in neurological diseases. (C) 2020 Elsevier Inc. All rights reserved.

关键词： 脑   神经病学   神经科学   病理学   综述  

摘要： 人脑组织库(简称脑库)是通过遗体器官组织捐献渠道进行的脑组织采集、存储、研究并资源共享,为医学研究者开展神经病学和神经科学研究而奠定基础的机构。脑库的发展伴随神经病学发展的始终:神经病学始于对个案脑组织的尸体解剖病理学检查,随着脑库建设可将神经病学再度带入崭新的认知领域,促进神经系统疾病新病种的发现与确定,对探索疾病的发生发展机制和新的治疗手段具有重要作用。本文拟从脑库发展史、国内外发展现状及其与神经病学的时代意义等方面进行阐述,并探讨我国脑库建设的机遇与挑战。

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摘要： 1.请打开本刊网址(htp://***),点击“投稿及审稿办公系统”,进行在线注册。2.注册后登录系统,并以第一作者的中文姓名在线提交稿件(请勿以通讯作者或姓名拼音提交稿件)。3.在网站首页下载中心下载《版权转让确认书》,签字并加盖公章后拍照或扫描成电子版发至2105933141@***,并在邮件主题中注明“第一作者姓名”及“投稿”字样,如“张三-投稿”。

摘要： 《临床神经病学杂志》系国家级神经病学专业性学术期刊。国内统一刊号CN 32-1337/R,国际标准刊号ISSN 1004-1648。曾荣获第二届全国优秀科技期刊奖及连续多次江苏省优秀期刊奖,并已入选中国科技核心期刊。2005年-2006年先后被美国化学文摘(CA)、俄罗斯文摘杂志(PK)、波兰哥白尼索引(IC)以及美国《乌利希国际期刊指南》四大数据库收录。本刊始终坚持“面向临床、面向基层、注重实用”的办刊宗旨.多年来已成为广大医务工作者.特别是神经科临床医师进行学术交流、更新知识的学术园地。

关键词： Aphasia   facial innervation   palate innervation   paralysis agitans   Parkinson's disease   William Rutherford Sanders  

摘要： William Rutherford Sanders (1828-1881) was an Edinburgh physician who occupied the Chair of Pathology at the University of Edinburgh from 1869 to 1881. All of his published output between 1865 and 1868 was concerned with neurology. In arguing that a patient did not have paralysis agitans, Sanders (1865) employed the term "Parkinson's disease" for the first time in the English-language literature to distinguish between the disorder that Parkinson (1817) termed "paralysis agitans" and other types of shaking palsies. He contributed a major chapter on the same topic to Russell Reynolds's A System of Medicine (1868). Sanders also investigated the innervation of the palate and facial muscles (1865), and in 1866 recorded the autopsy findings in two cases of aphasia. Here, for the first time in the English-language literature, he described findings that supported Broca's location of the representation of speech to a particular area of the left cerebral hemisphere.