Neurologic disease

神经系统疾病
  • 文章类型: Journal Article
    高级别神经胶质瘤(HGG)是最常见的原发性脑癌。它们的特征是宿主大脑的侵袭性生长和弥漫性浸润模式,严重限制了常规治疗的疗效和患者的预后。总体上仍然很穷。最近的工作描述了HGG相互作用的一套机制,主要是双向的,宿主大脑中的各种细胞类型,包括神经元,胶质细胞,免疫细胞,和血管元素来驱动肿瘤生长和侵袭。这些见解有可能激发急需的HGG治疗的新方法。这篇综述探讨了HGG与宿主大脑的相互作用,并考虑了它们是否以及如何被利用来获得治疗收益。
    High-grade gliomas (HGGs) are the commonest primary brain cancers. They are characterized by a pattern of aggressive growth and diffuse infiltration of the host brain that severely limits the efficacy of conventional treatments and patient outcomes, which remain generally poor. Recent work has described a suite of mechanisms via which HGGs interact, predominantly bidirectionally, with various cell types in the host brain including neurons, glial cells, immune cells, and vascular elements to drive tumor growth and invasion. These insights have the potential to inspire novel approaches to HGG therapy that are critically needed. This review explores HGG-host brain interactions and considers whether and how they might be exploited for therapeutic gain.
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  • 文章类型: Journal Article
    尽管下一代测序(NGS)取得了进展,对于许多神经系统综合征患者,基因诊断仍然难以捉摸。长读测序(LRS)和光学基因组作图(OGM)技术改进了重复DNA结构变异的检测和解释的现有能力。在单个单倍型上,同时还提供增强的断点分辨率。我们对两名已知染色体重排且不确定Sanger或NGS的患者进行了LRS和OGM。第一个病人,患有癫痫和发育迟缓的人,在两个染色体之间有复杂的易位,包括插入和倒置事件。第二个病人,有运动障碍的人,单个染色体上的倒位被多个较小的倒位和插入破坏。重排的序列水平分辨率确定了具有相关神经表型(MBD5,NKX2-1)的已知致病基因中或附近的非编码序列中的致病性断裂。这些特定的变体以前没有报道过,但预期的分子后果与以前报道的病例一致.随着LRS和OGM技术在临床试验中的使用增加和数据分析变得更加标准化,这些方法以及用于验证非编码变异效应的多组数据将提高诊断率,并增加具有与神经遗传病相关的已知基因的可检测致病变异的先证者的比例.
    Despite advances in next generation sequencing (NGS), genetic diagnoses remain elusive for many patients with neurologic syndromes. Long-read sequencing (LRS) and optical genome mapping (OGM) technologies improve upon existing capabilities in the detection and interpretation of structural variation in repetitive DNA, on a single haplotype, while also providing enhanced breakpoint resolution. We performed LRS and OGM on two patients with known chromosomal rearrangements and inconclusive Sanger or NGS. The first patient, who had epilepsy and developmental delay, had a complex translocation between two chromosomes that included insertion and inversion events. The second patient, who had a movement disorder, had an inversion on a single chromosome disrupted by multiple smaller inversions and insertions. Sequence level resolution of the rearrangements identified pathogenic breaks in noncoding sequence in or near known disease-causing genes with relevant neurologic phenotypes (MBD5, NKX2-1). These specific variants have not been reported previously, but expected molecular consequences are consistent with previously reported cases. As the use of LRS and OGM technologies for clinical testing increases and data analyses become more standardized, these methods along with multiomic data to validate noncoding variation effects will improve diagnostic yield and increase the proportion of probands with detectable pathogenic variants for known genes implicated in neurogenetic disease.
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  • 文章类型: Journal Article
    需要进一步研究以确定脑室腹膜分流术(VP)产妇最安全的分娩方式和麻醉管理。先前建议在有脑室腹膜分流的妇女中分娩是剖宫产。然而,对于VP分流功能正常的女性,阴道分娩和神经轴麻醉均被证明是安全的.我们介绍了一系列患有VP分流的产妇。确定了有VP分流的产妇,并指示了VP分流的位置,怀孕期间的神经系统症状,交货方式,麻醉类型,并对产后并发症进行了回顾。确定了40名患者,包括15名妇女和20名分娩。两名妇女在怀孕期间出现神经系统症状,一名妇女因视力模糊和共济失调而需要产后分流术。有十例剖宫产分娩和十例阴道分娩(八例正常自发,一个真空辅助,和一个镊子辅助)。进行了辅助阴道分娩以减少Valsalva,包括与分流功能障碍有关的神经系统症状的患者。阴道分娩,6人(60%)进行了硬膜外镇痛。剖宫产的麻醉包括神经轴麻醉(n=5)和全身麻醉(n=5)。在我们的队列中,接受VP分流术的女性接受了神经轴阻滞,无并发症.应向功能正常的VP分流的女性提供神经轴技术。
    Further study is needed to determine the safest mode of delivery and anesthetic management for parturients with ventriculoperitoneal shunts (VP). Prior recommendation for delivery in women with ventriculoperitoneal shunts was cesarean delivery. However, both vaginal delivery and neuraxial anesthesia have been shown to be safe in women with appropriately functioning VP shunts. We present a case series of parturients with VP shunt. Parturients with VP shunts were identified and VP shunt placement indications, neurologic symptoms during pregnancy, delivery mode, anesthetic type, and postpartum complications were reviewed. Forty patients were identified, and fifteen women with twenty deliveries were included. Two women experienced neurological symptoms during pregnancy and one required postpartum shunt revision for blurry vision and ataxia. There were ten cesarean deliveries and ten vaginal deliveries (eight normal spontaneous, one vacuum assisted, and one forceps assisted). Assisted vaginal deliveries were performed to decrease Valsalva including the patient with neurological symptoms related to shunt malfunction. Of the vaginal deliveries, six (60%) had epidural analgesia. Anesthesia for cesarean delivery included neuraxial anesthesia (n = 5) and general anesthesia (n = 5). In our cohort, women with VP shunt received neuraxial blockade without complication. Neuraxial techniques should be offered to women with appropriately functioning VP shunt.
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  • 文章类型: Journal Article
    本文讨论了患有神经源性下尿路功能障碍(NTUTD)的患者的理想神经源性膀胱管理团队。它强调了多元化团队的重要性,包括泌尿科医生,理疗师,神经科医生和其他人,协同工作,以防止并发症和提高患者的结果。由于各种神经状况和NULTD功能障碍模式的独特细微差别,概述了跨学科团队中不同专家的角色。本文介绍了3个团队模型:多学科,跨学科,和跨学科的,强调协作方法的好处。
    This article discusses the ideal neurogenic bladder management team for patients who have neurogenic lower urinary tract dysfunction (NLUTD). It emphasizes the importance of a diverse team, including urologists, physiatrists, neurologist and others, working collaboratively to prevent complications and enhance patient outcomes. Owing to the unique nuances of the various neurologic conditions and patterns of NLUTD dysfunction, the roles of different specialists in the interdisciplinary team are outlined. This article describes 3 team models: multidisciplinary, interdisciplinary, and transdisciplinary, highlighting the benefits of collaborative approaches.
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  • 文章类型: Review
    三甲胺-N-氧化物(TMAO)是一种常见的肠代谢产物。营养素中的胆碱在肠道微生物群的作用下形成TMA,它通过肝脏并最终形成TMAO。TMAO的初步研究集中在心血管疾病,但随着研究的进展,发现TAMO的作用是多系统的,与神经系统疾病的发展密切相关。肠道是人体内细菌浓度最高的器官,肠道菌群的组成和代谢会影响人体健康。作为连接中枢神经系统和胃肠道的双向通信轴,脑-肠轴为TMAO发挥作用提供了结构基础。本文将对TMA/TMAO与神经系统疾病的相关性进行综述,以期为神经系统疾病的治疗寻找新方向和新靶点。
    Trimethylamine-N-oxide (TMAO) is a common intestinal metabolite. The Choline in the nutrient forms TMA under the action of the gut microbiota, which passes through the liver and eventually forms TMAO. Initial studies of TMAO focused on cardiovascular disease, but as research progressed, TAMO\'s effects were found to be multisystem and closely related to the development of neurological diseases. Intestinal tract is the organ with the largest concentration of bacteria in human body, and the composition and metabolism of gut microbiota affect human health. As a two-way communication axis connecting the central nervous system and the gastrointestinal tract, the brain-gut axis provides the structural basis for TMAO to play its role. This article will review the correlation between TMA/TMAO and neurological diseases in order to find new directions and new targets for the treatment of neurological diseases.
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  • 文章类型: Journal Article
    脑脊液的分析有诊断意义,预后,和治疗马的神经系统疾病的价值。有不同的获取脑脊液的方法,C1和C2椎骨之间的收集是一种较新的方法,这使得手术可以在站立的病人身上进行,没有全身麻醉的限制,并且血液对样品的污染较低,把自己作为一个实际的选择。这项研究评估了通过寰枢椎穿刺进行脑脊液收集的健康马匹的局部硬脑膜阻滞的有效性和安全性,以及通过该程序获得的样品的质量。被提交给身体,化学,和细胞学分析。考虑到疼痛等方面对动物进行评估,灵敏度,水肿的存在,温度变化,和收集后的超声改变。穿刺后观察到局部离散变化,并且该程序被认为是安全且易于执行的。利多卡因阻滞可以减少针头通过硬脑膜引起的反应,获得的样品显示出令人满意的质量,实验室结果与文献中汇编的值一致。在硬脑膜阻滞组的动物中有70%(7/10)观察到短暂的高温,和80%(8/10)的患者来自对照组,总共75%的个体被评估。手术后4至12小时观察到直肠温度的变化,并且在没有干预的情况下通过24小时评估完全解决。
    The analysis of cerebrospinal fluid has diagnostic, prognostic, and therapeutic value in neurological illnesses in horses. There are different methods for obtaining cerebrospinal fluid, with the collection between the C1 and C2 vertebrae being a more recent methodology, which allows the procedure to be performed in standing patients, without the limitations of general anesthesia and with a low contamination of the sample with blood, presenting itself as a practical alternative. This study evaluated the efficacy and safety of a local dural blockade in healthy horses submitted to cerebrospinal fluid collection by atlantoaxial puncture and the quality of the samples obtained by this procedure, which were submitted to physical, chemical, and cytological analyses. The animals were evaluated considering aspects such as pain, sensitivity, the presence of edema, temperature variations, and ultrasonographic alterations post-collection. Discrete local changes were observed after the puncture, and the procedure was considered safe and simple to perform. Lidocaine blockade could reduce the reaction elicited by the needle passing through the dura mater, and the samples obtained showed satisfactory quality and laboratory results consistent with the values compiled in the literature. Transient hyperthermia was observed in 70% (7/10) of the animals in the dural blockade group, and 80%(8/10) of the patients from the control group, totalizing 75% of all individuals evaluated. The rectal temperature alteration was observed 4 to 12 hours after the procedure and was entirely resolved without intervention by the 24-hour evaluation.
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  • 文章类型: Journal Article
    随着全球人口老龄化,神经退行性疾病的患病率正在激增。这些疾病有多方面的发病机制,与遗传和环境因素交织在一起。新兴的研究强调了饮食对健康状况的发展和进展的深远影响。间歇性禁食(IF),一种越来越被接受和推荐的饮食模式,已证明在改善神经生理功能和减轻病理损伤方面具有潜力,而不良反应很少。虽然IF的有益影响的确切机制尚未完全了解,肠道微生物群及其代谢物被认为是介导这些作用的关键。这篇综述试图彻底检查当前关于由IF引起的肠道微生物群和代谢物谱变化的研究,以及它们对神经健康的可能后果。它还强调了饮食策略作为神经系统疾病患者的临床考虑的重要性。
    As the global population ages, the prevalence of neurodegenerative diseases is surging. These disorders have a multifaceted pathogenesis, entwined with genetic and environmental factors. Emerging research underscores the profound influence of diet on the development and progression of health conditions. Intermittent fasting (IF), a dietary pattern that is increasingly embraced and recommended, has demonstrated potential in improving neurophysiological functions and mitigating pathological injuries with few adverse effects. Although the precise mechanisms of IF\'s beneficial impact are not yet completely understood, gut microbiota and their metabolites are believed to be pivotal in mediating these effects. This review endeavors to thoroughly examine current studies on the shifts in gut microbiota and metabolite profiles prompted by IF, and their possible consequences for neural health. It also highlights the significance of dietary strategies as a clinical consideration for those with neurological conditions.
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  • 文章类型: Journal Article
    氧化甾醇和植物甾醇是在健康个体的组织和血清中以显著低水平存在的甾醇化合物。大量证据表明,它们可以用作人类疾病或胆固醇吸收的生物标志物。越来越多的报道表明循环或组织氧固醇是心血管和神经退行性疾病或癌症的推定生物标志物。到目前为止,大多数研究都是在小型研究人群中进行的。为了实现常规生物标志物的使用,大型前瞻性队列研究是绝对必要的.这个,再次,将需要在不同实验室对氧固醇分析方法进行彻底标准化,现在采用不同的技术,导致测量的氧固醇水平不一致。氧固醇生物标志物的常规使用还需要开发适用于高通量平台的新的靶向分析方法。植物甾醇作为生物标志物的最重要用途涉及它们作为胆固醇吸收标志物的用途。为了实现这一点,(1)它们的定量分析应在常规脂质实验室中进行,(2)应该普遍承认,胆固醇代谢的概况可以揭示动脉粥样硬化性心血管疾病(ASCVD)发展的风险,(3)ASCVD风险调查中应包括对胆固醇代谢概况的筛查.这应该这样做,例如在有早期发作或频繁ASCVD病史的家庭和18-20岁的年轻人,排除高胆固醇吸收的存在。高胆固醇吸收家庭中的个体需要从年轻成年期开始的预防措施,以抑制动脉粥样硬化的可能发展和进展。
    Oxysterols and phytosterols are sterol compounds present at markedly low levels in tissues and serum of healthy individuals. A wealth of evidence suggests that they could be employed as biomarkers for human diseases or for cholesterol absorption.An increasing number of reports suggest circulating or tissue oxysterols as putative biomarkers for cardiovascular and neurodegenerative diseases or cancers. Thus far most of the studies have been carried out on small study populations. To achieve routine biomarker use, large prospective cohort studies are absolutely required. This, again, would necessitate thorough standardization of the oxysterol analytical methodology across the different laboratories, which now employ different technologies resulting in inconsistencies in the measured oxysterol levels. Routine use of oxysterol biomarkers would also necessitate the development of a new targeted analytical methodology suitable for high-throughput platforms.The most important use of phytosterols as biomarkers involves their use as markers for cholesterol absorption. For this to be achieved, (1) their quantitative analyses should be available in routine lipid laboratories, (2) it should be generally acknowledgment that the profile of cholesterol metabolism can reveal the risk of the development of atherosclerotic cardiovascular diseases (ASCVD), and (3) screening of the profile of cholesterol metabolism should be included in the ASCVD risk surveys. This should be done e.g. in families with a history of early onset or frequent ASCVD and in young adults aged 18-20 years, to exclude the presence of high cholesterol absorption. Individuals in high cholesterol absorption families need preventive measures from young adulthood to inhibit the possible development and progression of atherosclerosis.
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  • 文章类型: Randomized Controlled Trial
    肥胖是发生多发性硬化症(MS)和MS相关残疾的危险因素。在MS(pwMS)患者中,行为减肥干预的有效性仍然未知。
    检查基于小组的远程健康减肥干预是否会在pwMS和肥胖症中产生临床上显着的体重减轻。
    将71例pwMS随机分配到体重减轻干预或照常治疗(TAU)。为期6个月的计划促进了减少卡路里和增加体力活动的既定指南。人体测量,移动性任务,自我报告问卷,和加速度测量法用于评估随访时的变化。
    与TAU组的0.7%相比,治疗组的平均体重减轻百分比为8.6%(p<.001)。65%的干预参与者实现了临床上有意义的体重减轻(5%)。与TAU参与者相比,治疗组的参与者每周进行46.2分钟的中度至剧烈的体育锻炼(p=0.017),并显示出生活质量的改善(p=0.012)。体重减轻与改善的活动性(p=.003)和降低的疲劳性(p=.008)相关。
    研究结果表明,行为干预对pwMS和肥胖的有效性,在治疗条件下,三分之二的参与者具有临床上显着的体重减轻。体重减轻还可导致改善的活动能力和生活质量。
    UNASSIGNED: Obesity is a risk factor for developing multiple sclerosis (MS) and MS-related disability. The efficacy of behavioral weight loss interventions among people with MS (pwMS) remains largely unknown.
    UNASSIGNED: Examine whether a group-based telehealth weight loss intervention produces clinically significant weight loss in pwMS and obesity.
    UNASSIGNED: Seventy-one pwMS were randomized to the weight loss intervention or treatment-as-usual (TAU). The 6-month program promoted established guidelines for calorie reduction and increased physical activity. Anthropometric measurements, mobility tasks, self-report questionnaires, and accelerometry were used to assess changes at follow-up.
    UNASSIGNED: Mean percent weight loss in the treatment group was 8.6% compared to 0.7% in the TAU group (p < .001). Sixty-five percent of participants in the intervention achieved clinically meaningful weight loss (⩾ 5%). Participants in the treatment group engaged in 46.2 minutes/week more moderate-to-vigorous physical activity than TAU participants (p = .017) and showed improvements in quality of life (p = .012). Weight loss was associated with improved mobility (p = .003) and reduced fatiguability (p = .008).
    UNASSIGNED: Findings demonstrate the efficacy of a behavioral intervention for pwMS and obesity, with clinically significant weight loss for two-thirds of participants in the treatment condition. Weight loss may also lead to improved mobility and quality of life.
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  • 文章类型: Journal Article
    中风是世界上第三个长期残疾的原因。大约80%的中风患者有生物运动功能受损,超过一半的患者无法恢复手臂功能,导致运动控制障碍,严重丧失社会独立性。因此,康复在减少患者残疾方面起着关键作用,3D打印(3DP)在相关领域显示出有趣的改进,由于生产定制的可能性,生态可持续和成本有效的矫形器。这项研究调查了3DP矫形器在康复中的临床使用与传统矫形器相比,关注3DP技术之间的相关性,治疗和结果。我们筛选了来自PubMed的138篇文章,Scopus和WebofScience,选择符合纳入标准的10篇文章,随后对其进行了系统审查。结果表明,3DP提供了大量的优势,在上肢矫形器设计的病人的需要。此外,七项研究活动使用可生物降解/可回收材料,强调经过验证的3DP解决方案在临床康复环境中的巨大潜力。这项研究的目的是强调3DP如何克服标准医疗设备的局限性,以支持临床医生。实施医疗保健4.0期间的生物工程师和创新经理。
    Stroke represents the third cause of long-term disability in the world. About 80% of stroke patients have an impairment of bio-motor functions and over half fail to regain arm functionality, resulting in motor movement control disorder with serious loss in terms of social independence. Therefore, rehabilitation plays a key role in the reduction of patient disabilities, and 3D printing (3DP) has showed interesting improvements in related fields, thanks to the possibility to produce customized, eco-sustainable and cost-effective orthoses. This study investigated the clinical use of 3DP orthosis in rehabilitation compared to the traditional ones, focusing on the correlation between 3DP technology, therapy and outcomes. We screened 138 articles from PubMed, Scopus and Web of Science, selecting the 10 articles fulfilling the inclusion criteria, which were subsequently examined for the systematic review. The results showed that 3DP provides substantial advantages in terms of upper limb orthosis designed on the patient\'s needs. Moreover, seven research activities used biodegradable/recyclable materials, underlining the great potential of validated 3DP solutions in a clinical rehabilitation setting. The aim of this study was to highlight how 3DP could overcome the limitations of standard medical devices in order to support clinicians, bioengineers and innovation managers during the implementation of Healthcare 4.0.
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