Neurological

Neurological
  • DOI:
    文章类型: Journal Article
    Neuroplasticity is an essential mechanism by which the nervous system shapes and adapts according to functional requirements. Evidence suggests that physical exercise induces a cascade of cellular processes that favours brain plasticity. The Brain Derived Neurotrophic Factor (BDNF) is a neurotrophin closely linked to neuroplasticity that can be increased due to exercise. To verify the effects of therapeutic exercise on neuroplasticity and/or peripheral BDNF levels in neurological conditions in adults, such as stroke, Parkinson\'s and Alzheimer\'s diseases and mild cognitive impairment and address its clinical relevance in the treatment of neurological dysfunctions. A systematic review was carried using PUBMED, Web of Science and Scopus databases. Inclusion criteria were: randomized controlled trials or pilot studies; humans with age > 18 yrs with neurological condition; English language; score ≥ 6 in PEDro Scale (moderate to high quality). Reviews, meta-analyses and other articles that did not meet the criteria were excluded. The PRISMA methodology was applied for studies\' selection. A total of 9 studies were selected for a systematic and comprehensive analysis. According to these studies, moderate to high intensity aerobic exercise (AE), increases the level of peripheral BDNF and positively influences functional gains in neurological conditions. Larger outcomes are observed in protocols with minimum session duration of 30 minutes, frequency of 3 times/week and intervention duration of 4 weeks. Current evidence shows that moderate to high intensity AE induces neuroplasticity in neurological patients, thus being a fundamental therapeutic strategy to include in interventions aiming to repair/delay neurological dysfunctions.
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  • 文章类型: Journal Article
    需要靶向中枢神经系统(CNS)的高效腺相关病毒(AAV)来为遗传性神经障碍提供安全有效的治疗。本研究的目的是比较两种AAV衣壳在三种不同递送途径中的器官特异性转导效率。我们在小鼠中使用以下递送途径将AAV9-CBA-fLucYFP与AAV-DJ-CBA-fLucYFP进行了比较:脑室内(ICV)1×1012vg/kg,鞘内(IT)1×1012vg/kg,静脉注射(IV)1×1013vg/kg体重。我们的评估显示,在ICV和IT管理部门之后,与AAV9相比,AAV-DJ显示整个CNS中载体基因组(vg)摄取显著增加。通过IV路线,AAV9显示CNS中vg摄取显著增加。然而,与AAV9相比,在使用IT和IV递送途径施用AAV-DJ后,在脱靶器官(肾脏和肝脏)中检测到显著更少的vg。vgs的分布与转基因转录水平密切相关,荧光素酶酶活性,和YFP的免疫荧光检测。总的来说,在两个向量之间,AAV-DJ导致在CNS组织中更好的靶向和表达,同时在肝脏和肾脏中脱靶和表达降低。我们的发现支持进一步检查AAV-DJ作为治疗神经系统疾病的基因治疗衣壳。
    Highly efficient adeno associated viruses (AAVs) targeting the central nervous system (CNS) are needed to deliver safe and effective therapies for inherited neurological disorders. The goal of this study was to compare the organ-specific transduction efficiencies of two AAV capsids across three different delivery routes. We compared AAV9-CBA-fLucYFP to AAV-DJ-CBA-fLucYFP using the following delivery routes in mice: intracerebroventricular (ICV) 1 × 1012 vg/kg, intrathecal (IT) 1 × 1012 vg/kg, and intravenous (IV) 1 × 1013 vg/kg body weight. Our evaluations revealed that following ICV and IT administrations, AAV-DJ demonstrated significantly increased vector genome (vg) uptake throughout the CNS as compared to AAV9. Through the IV route, AAV9 demonstrated significantly increased vg uptake in the CNS. However, significantly fewer vgs were detected in the off-target organs (kidney and liver) following administration of AAV-DJ using the IT and IV delivery routes as compared to AAV9. Distributions of vgs correlate well with transgene transcript levels, luciferase enzyme activities, and immunofluorescence detection of YFP. Overall, between the two vectors, AAV-DJ resulted in better targeting and expression in CNS tissues paired with de-targeting and reduced expression in liver and kidneys. Our findings support further examination of AAV-DJ as a gene therapy capsid for the treatment of neurological disorders.
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  • 文章类型: Journal Article
    背景:对于软脑膜转移(LM)患者的临床神经学评估,尚无有效的工具。然而,疾病过程中的临床检查指导医疗管理,是临床试验反应评估的一部分。因为神经影像学可能并不总是由于快速的临床恶化而获得,LM的临床神经学评估至关重要,标准化对于最大限度地减少评估者的分歧很重要。
    方法:RANO-LM组启动了一个两步流程,旨在改善和规范LM患者的临床评估。我们在此报告第一步:建立共识记分卡。工作组举行了9次虚拟会议,以定义有关神经系统评估的一般建议以及应进行测试的选定感兴趣领域。
    结果:选择了十四个神经症状和体征领域:意识水平,认知,恶心和呕吐,愿景,眼球运动,面部力量,听力,吞咽,演讲,肢体力量,肢体共济失调,走路,膀胱肠功能。对于每个项目,关于如何执行评估的明确说明提供了0和2之间的评分标准。患者的一般临床状况和类固醇的使用情况,止痛药,和抗催吐剂应该记录在案。以前的脑转移或癌症治疗的神经系统后遗症应在基线评估时进行评估;当症状或体征可能与LM以外的其他疾病有关时,应指定。
    结论:已建立了用于临床评估的经修订的NANO-LM共识记分卡。该提案的国际前瞻性验证研究目前正在进行中(NCT06417710)。
    BACKGROUND: There are no validated tools for the clinical neurological assessment of patients with leptomeningeal metastases (LM). However, clinical examination during the course of the disease guides medical management and is part of response assessment in clinical trials. Because neuroimaging may not always be obtained owing to rapid clinical deterioration, clinical neurological assessment of LM is essential, and standardization Is important to minimize rater disagreement.
    METHODS: The RANO-LM group launched a 2-steps process, aiming at improving and standardizing the clinical assessment of patients with LM. We report here on the first step: the establishment of a consensus scorecard. The task force had 9 virtual meetings to define general recommendations on neurological assessment and selected domains of interest that should be tested.
    RESULTS: Fourteen domains of neurological symptoms and signs were selected: level of consciousness, cognition, nausea and vomiting, vision, eye movement, facial strength, hearing, swallowing, speech, limb strength, limb ataxia, walking, bladder bowel functions. For each item, a clear instruction on how to perform the assessment is provided with scoring criteria between 0 and 2. The general clinical status of the patient and use of steroids, pain medications, and anti-emetics should be documented. Neurological sequelae from previous brain metastases or cancer treatment should be rated at the baseline evaluation; it should be specified when symptoms or signs may be related to a condition other than LM.
    CONCLUSIONS: A revised NANO-LM consensus scorecard for clinical assessment has been established. An international prospective validation study of the proposal is currently ongoing (NCT06417710).
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  • 文章类型: Journal Article
    最近,磁场(MF)由于其潜在的治疗应用和生物学效应而受到了广泛的关注。这篇综述全面分析了MFs的细胞和分子影响,专注于体外和体内研究。我们研究了MFs影响细胞行为的机制,包括基因表达的修饰,蛋白质合成,和细胞信号通路。MFs与细胞成分如离子通道的相互作用,膜,分析细胞骨架,以及它们对细胞增殖等过程的影响,分化,和凋亡。分子洞察提供了MFs如何调节氧化应激和炎症反应,在各种病理条件下至关重要。此外,我们探索了MF在再生医学中的治疗潜力,癌症治疗,和神经退行性疾病。通过综合目前的发现,本文旨在阐明MFs的复杂生物效应,从而促进其在医学和生物技术领域的优化应用。
    Recently, magnetic fields (MFs) have received major attention due to their potential therapeutic applications and biological effects. This review provides a comprehensive analysis of the cellular and molecular impacts of MFs, with a focus on both in vitro and in vivo studies. We investigate the mechanisms by which MFs influence cell behavior, including modifications in gene expression, protein synthesis, and cellular signaling pathways. The interaction of MFs with cellular components such as ion channels, membranes, and the cytoskeleton is analyzed, along with their effects on cellular processes like proliferation, differentiation, and apoptosis. Molecular insights are offered into how MFs modulate oxidative stress and inflammatory responses, which are pivotal in various pathological conditions. Furthermore, we explore the therapeutic potential of MFs in regenerative medicine, cancer treatment, and neurodegenerative diseases. By synthesizing current findings, this article aims to elucidate the complex bioeffects of MFs, thereby facilitating their optimized application in medical and biotechnological fields.
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  • 文章类型: Case Reports
    背景:韦尼克脑病是一种由硫胺素缺乏引起的神经系统疾病,常见于酒精人群,但也涉及其他可能导致硫胺素缺乏的情况。Wernicke脑病的识别通常取决于临床医生敏锐的能力来检测其典型的三联征;然而,大多数情况下没有完整的星座,这使Wernicke脑病的及时识别复杂化。
    方法:本病例报告描述了一名鼻咽癌患者,在同步放化疗后出现了异常的眼部功能和共济失调,没有酗酒史.在放射检查的帮助下,他得到了及时的诊断和治疗;然而,他的症状在随访期间没有完全缓解.
    结论:对于有神经系统症状的恶性肿瘤患者,临床医生应考虑韦尼克脑病的可能性,并提供预防性硫胺素治疗.
    BACKGROUND: Wernicke encephalopathy is a neurological disorder caused by thiamine deficiency, commonly seen in alcoholic populations but also involving other circumstances that may lead to thiamine deficiency. The recognition of Wernicke encephalopathy often depends on clinicians\' keen ability to detect its typical triad of features; however, most cases do not present with the full constellation of signs, which complicates the timely identification of Wernicke encephalopathy.
    METHODS: This case report describes a patient with nasopharyngeal carcinoma who developed abnormal ocular function and ataxia following concurrent chemoradiotherapy, without a history of alcohol abuse. With the aid of radiological examinations, he received a timely diagnosis and treatment; however, his symptoms did not fully resolve during follow-up.
    CONCLUSIONS: For patients with malignant tumors exhibiting neurological symptoms, clinicians should consider the possibility of Wernicke encephalopathy and provide prophylactic thiamine therapy.
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  • 文章类型: Journal Article
    背景:利妥昔单抗(RTX)用于肾外活动的系统性红斑狼疮(SLE)难治性病例,包括神经和/或精神病(N/P)表现。然而,随机对照试验的证据有限.
    目的:本研究旨在对RTX治疗成人难治性SLE伴N/P表现的有效性和安全性进行综合分析。
    方法:本研究进行数据库电子检索和统计分析。
    结果:PubMed中的电子搜索,认识论,2023年5月,ICTRP确定了20项研究(25份报告)。共纳入59名患者(53名女性;90%),平均年龄为33.5±10.6岁,中位病程为3.5年(范围,0.08至25.0),在RTX治疗后随访,中位时间为12个月(范围,3.0to46.2).临床反应(部分或主要)率为90%(95%CI,83至96)(n=57例患者)。三分之一的应答者在中位时间9.5个月后复发(范围,3.0至33.0)。系统性红斑狼疮疾病活动指数(SLEDAI)(n=13)的RTX前/RTX后汇总评分为19±15/7±5,而神经系统性不列颠群岛狼疮评估组(BILAG)(n=29)为A/D(13),A/C(5),B/D(7),B/C(2),A/A(2)。没有情绪障碍的患者有更高的机会临床反应{相对风险(RR)1.4(1.03至1.48)}。从RTX治疗中获益最多的患者是精神病患者(出现重大临床反应的机会较高;RR1.9(1.02至2.34)),无急性混淆状态(复发机会较低;RR0.08(0.006至0.791)),并且病程<3年(复发机会较低;RR0.18(0.014至0.992))。治疗期间感染率为33%(7/21)。
    结论:RTX治疗效果良好。安全性结果的汇总证据有限且确定性低。
    Rituximab (RTX) is used off-label for refractory cases of systemic lupus erythematosus (SLE) with extrarenal activity, including neurological and/or psychiatric (N/P) presentations. However, evidence from randomized controlled trials is limited.
    This study aimed to conduct a pooled analysis of the effectiveness and safety of RTX therapy for adult refractory SLE with N/P manifestations.
    Electronic searches in PubMed, Epistemonikos, and ICTRP databases and statistical analysis were conducted in May 2023.
    Electronic searches identified 20 studies (25 reports). A total of 59 patients (53 females; 90%) were included, with a mean age of 33.5±10.6 years and a median disease duration of 3.5 years (range, 0.08 to 25.0) who were followed up post-RTX therapy for a median time of 12 months (range, 3.0 to 46.2). The rate of clinical response (partial or major) was 90% (95% CI, 83 to 96) (n = 57 patients). A third of responders relapsed after a median time of 9.5 months (range, 3.0 to 33.0). Pooled pre-RTX/post-RTX scores for Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) (n = 13) were 19±15/7±5 and for neurological British Isles Lupus Assessment Group (BILAG) (n = 29) were A/D (13), A/C (5), B/D (7), B/C (2), and A/A (2). Patients without mood disorder had a higher chance of clinical response {relative risk (RR) 1.4 (1.03 to 1.48)}. Patients who benefited the most from RTX therapy were those with psychosis (a higher chance of major clinical response; RR 1.9 (1.02 to 2.34)), without acute confusional state (a lower chance of relapse; RR 0.08 (0.006 to 0.791)), and with disease duration <3 years (a lower chance of relapse; RR 0.18 (0.014 to 0.992)). Infection rate during treatment was 33% (7/21).
    RTX therapy had good effectiveness. The pooled evidence for safety outcomes was limited and of low certainty.
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  • 文章类型: Case Reports
    目的:报道一例重度溴甲灵中毒猫初次成功治疗后延迟死亡的病例。
    方法:一只2岁的雄性家养短毛猫因溴甲烷中毒和进行性神经系统衰退而转诊。在转诊时,这只猫是非卧床四足动物,所有四个肢体的运动功能都很弱,并表现出迟钝的状态。在住院的前4小时内,猫的神经状态继续迅速下降,和渗透疗法,皮质类固醇,和脂质内给药。治疗方案还包括左乙拉西坦,硫胺素,胆甾胺,维生素E,还有银杏叶.摄入溴甲基灵六天后,这只猫表现出明显的神经系统改善,接近正常的状态和轻度的四轻瘫,并已出院。猫继续在家里做得很好,改善了神经状况和功能。出院后9天,那只猫在抵达时被发现死亡。尸检显示,白质海绵状变性继发的经椎间孔脑疝和颅内压升高是死亡的原因。
    对于作者的知识,这是一只猫在接受重度溴甲灵中毒治疗后,尽管最初的神经系统有所改善,但仍延迟死亡的第一份报告。
    OBJECTIVE: To report a case of delayed death after initial successful treatment of severe bromethalin intoxication in a cat.
    METHODS: A 2-year-old neutered male domestic shorthair cat presented as a referral for bromethalin toxicosis and progressive neurological decline. At the time of referral, the cat was nonambulatory tetraparetic with minimal motor function in all 4 limbs and exhibited a dull mentation. Within the first 4 hours of hospitalization, the cat\'s neurological status continued to rapidly decline, and osmotherapy, corticosteroids, and intralipids were administered. The treatment regimen also included levetiracetam, thiamine, cholestyramine, vitamin E, and gingko biloba. Six days after bromethalin ingestion, the cat displayed marked neurological improvement with near normal mentation and mild tetraparesis and was discharged. The cat continued to do well at home with improving neurological status and function. Nine days after discharge, the cat was presented dead on arrival. Postmortem examination revealed transforaminal brain herniation secondary to spongy degeneration of the white matter and increased intracranial pressure as the cause of death.
    UNASSIGNED: To the authors\' knowledge, this is the first report of a cat that suffered delayed death despite initial neurological improvement after being treated for severe bromethalin toxicosis.
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  • 文章类型: Journal Article
    谷氨酸激活NMDAR,显著影响多个过程,如学习,记忆,突触整合,和中枢神经系统的兴奋性传递。NMDAR的不受控激活是突触功能障碍的重要原因。具有正常功能的NMDAR和突触对于维持神经元通信至关重要。此外,NMDAR和突触功能的功能障碍可能导致神经元水平的神经系统疾病的发展;因此,用拮抗剂靶向NMDAR对抗神经系统疾病是一种有希望的途径.最近发表的关于中风等不同类型脑部疾病的动物研究结果,癫痫,耳鸣,共济失调,老年痴呆症,帕金森病,和脊髓损伤已证明有希望的治疗范围。几种NMDA受体拮抗剂,比如美金刚,MK801氯胺酮,ifenprodil,加环利定,金刚烷胺,胍丁胺,等。,对不同的脑疾病小鼠模型显示出令人鼓舞的结果。鉴于神经元组织良好的NMDA受体系统的不同亚基的独特表达。它可能会导致开发专门针对某些受体亚型的药物。对于未来的研究员来说,开展更具针对性的研究和试验对于充分了解和开发具有良好临床效果和潜在神经保护特性的高度特异性药物至关重要。
    Glutamate activates the NMDARs, significantly affecting multiple processes such as learning, memory, synaptic integration, and excitatory transmission in the central nervous system. Uncontrolled activation of NMDARs is a significant contributor to synaptic dysfunction. Having a properly functioning NMDAR and synapse is crucial for maintaining neuronal communication. In addition, the dysfunction of NMDAR and synapse function could contribute to the development of neurological disorders at the neuronal level; hence, targeting NMDARs with antagonists in the fight against neurological disorders is a promising route. Recently published results from the animal study on different kinds of brain diseases like stroke, epilepsy, tinnitus, ataxia, Alzheimer\'s disease, Parkinson\'s disease, and spinal cord injury have demonstrated promising therapeutic scopes. Several NMDA receptor antagonists, such as memantine, MK801, ketamine, ifenprodil, gacyclidine, amantadine, agmatine, etc., showed encouraging results against different brain disease mouse models. Given the unique expression of different subunits of the well-organized NMDA receptor system by neurons. It could potentially lead to the development of medications specifically targeting certain receptor subtypes. For a future researcher, conducting more targeted research and trials is crucial to fully understand and develop highly specific medications with good clinical effects and potential neuroprotective properties.
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  • 文章类型: Journal Article
    弓形虫病作为一种人畜共患疾病,在世界范围内分布,可以感染广泛的动物宿主,以及至少三分之一的世界人口。这种疾病在免疫功能正常的个体中通常是轻度或无症状的,但是休眠的组织囊肿在宿主的寿命中存活,特别是在大脑中,称为潜伏弓形虫病(LT)。最近的研究表明,LT可以具有某些神经系统,对人类包括精神分裂症的免疫心理和行为影响,双相情感障碍,老年痴呆症,抑郁症,自杀焦虑和睡眠障碍。LT效应是有争议的,它们的确切作用机制尚未完全了解。这篇综述旨在概述潜在的影响,它们的基本机制包括神经递质水平的改变,中枢神经系统的免疫激活和氧化应激的诱导。此外,LT的有益效果,并在操纵假设的框架内解释影响,最后,讨论了当前研究的挑战和局限性。
    Toxoplasmosis as a zoonotic disease has a worldwide distribution and can infect a wide range of animal hosts, as well as at least one third of the world\'s human population. The disease is usually mild or asymptomatic in immunocompetent individuals, but dormant tissue cysts survive especially in the brain for the host lifespan, known as latent toxoplasmosis (LT). Recent studies suggest that LT can have certain neurological, immunological psychological and behavioural effects on human including schizophrenia, bipolar disorder, Alzheimer\'s disease, depression, suicide anxiety and sleeping disorders. LT effects are controversial, and their exact mechanisms of action is not yet fully understood. This review aims to provide an overview of the potential effects, their basic mechanisms including alteration of neurotransmitter levels, immune activation in the central nervous system and induction of oxidative stress. Additionally, beneficial effects of LT, and an explanation of the effects within the framework of manipulation hypothesis, and finally, the challenges and limitations of the current research are discussed.
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  • 文章类型: Journal Article
    背景:脊髓灰质炎患者全膝关节置换术(TKA)的生存率仍然是一个有争议的话题,原因是术后复发的高复发率。本研究旨在报道TKA在脊髓灰质炎患者中的长期生存率。使用意大利假体植入学注册的数据。
    方法:进行了一项基于注册的人群研究,利用EmiliaRomagna矫形外科植入物注册(RIPO-注册植入前Ortopedica)的数据。该队列包括71例接受TKA的脊髓灰质炎相关关节炎患者。该研究评估和分析了人口统计数据,植入物类型,固定方法,插入类型,和约束水平。此外,收集了术前和术后临床和功能膝关节学会评分(KSS)的差异。
    结果:八个植入物需要翻修手术(16%),3名患者死亡(6.1%),10年生存率为86.6%,15年生存率为53.9%。无菌性松动是翻修的主要原因,占故障的37.5%,其次是刀片磨损(25%)。在约束水平和植入物存活之间没有发现统计学上显著的相关性(p=0.0887,log-rank)。术后临床和功能KSS均有改善。
    结论:TKA是膝关节固定术的可行替代方法,在适当选择的患者中,由于其高生存率,可能是关节变性的首选治疗方法。尽管这些案件很复杂,TKA能有效缓解关节疼痛,不稳定性,和角度偏差,从而保持膝关节功能。
    BACKGROUND: The survival of total knee arthroplasty (TKA) in patients with poliomyelitis remains a debated topic due to the high recurrence of postoperative genu recurvatum. This study aims to report the long-term survival of TKA in patients with poliomyelitis, using data from the Italian Register of Prosthetic Implantology.
    METHODS: A registry-based population study was conducted, utilizing data from the Emilia Romagna orthopedic arthroplasty implants registry (RIPO - Registro Implantologia Protesica Ortopedica). The cohort consisted of 71 patients with poliomyelitis-related arthritis who underwent TKA. The study assessed and analyzed demographic data, implant type, fixation method, insert type, and level of constraint. Additionally, variations in preoperative and postoperative both clinical and functional Knee Society Scores (KSS) were collected.
    RESULTS: Eight implants required revision surgery (16%), and three patients died (6.1%), resulting in a 10-year survival rate of 86.6% and a 15-year survival rate of 53.9%. Aseptic loosening was the primary cause of revision, accounting for 37.5% of failures, followed by insert wear (25%). No statistically significant correlation was found between the level of constraint and implant survival (p=0.0887, log-rank). Both the clinical and functional KSS improved postoperatively.
    CONCLUSIONS: TKA is a viable alternative to knee arthrodesis and, in properly selected patients, might represent the first-choice treatment for articular degeneration due to its high survivorship. Despite the complexity of these cases, TKA can effectively alleviate articular pain, instability, and angular deviation, thereby preserving knee functionality.
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