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Application of Muscle Synergies for Gait Rehabilitation After Stroke: Implications for Future Research. 中风后步态康复中肌肉协同作用的应用:对未来研究的启示
IF 3.2 Q2 CLINICAL NEUROLOGY Pub Date : 2024-11-13 DOI: 10.3390/neurolint16060108
Jaehyuk Lee, Kimyung Kim, Youngchae Cho, Hyeongdong Kim

Background/objective: Muscle synergy analysis based on machine learning has significantly advanced our understanding of the mechanisms underlying the central nervous system motor control of gait and has identified abnormal gait synergies in stroke patients through various analytical approaches. However, discrepancies in experimental conditions and computational methods have limited the clinical application of these findings. This review seeks to integrate the results of existing studies on the features of muscle synergies in stroke-related gait abnormalities and provide clinical and research insights into gait rehabilitation.

Methods: A systematic search of Web of Science, PubMed, and Scopus was conducted, yielding 10 full-text articles for inclusion.

Results: By comprehensively reviewing the consistencies and differences in the study outcomes, we emphasize the need to segment the gait cycle into specific phases (e.g., weight acceptance, push-off, foot clearance, and leg deceleration) during the treatment process of gait rehabilitation and to develop rehabilitation protocols aimed at restoring normal synergy patterns in each gait phase and fractionating reduced synergies.

Conclusions: Future research should focus on validating these protocols to improve clinical outcomes and introducing indicators to assess abnormalities in the temporal features of muscle synergies.

背景/目的:基于机器学习的肌肉协同分析极大地推动了我们对中枢神经系统运动控制步态机制的理解,并通过各种分析方法发现了中风患者的异常步态协同。然而,实验条件和计算方法的差异限制了这些发现的临床应用。本综述旨在整合现有关于中风相关步态异常中肌肉协同特征的研究成果,为步态康复提供临床和研究启示:方法:对 Web of Science、PubMed 和 Scopus 进行了系统检索,共收录了 10 篇全文文章:通过全面回顾研究结果的一致性和差异性,我们强调在步态康复治疗过程中,有必要将步态周期划分为特定阶段(如体重接受、推起、足部清理和腿部减速),并制定康复方案,旨在恢复每个步态阶段的正常协同模式,并分化减弱的协同作用:未来的研究应侧重于验证这些方案,以改善临床效果,并引入指标来评估肌肉协同作用的时间特征异常。
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引用次数: 0
Utilization of Single-Pulse Transcranial-Evoked Potentials in Neurological and Psychiatric Clinical Practice: A Narrative Review. 单脉冲经颅诱发电位在神经和精神科临床实践中的应用:叙述性综述。
IF 3.2 Q2 CLINICAL NEUROLOGY Pub Date : 2024-11-11 DOI: 10.3390/neurolint16060106
Hilla Fogel, Noa Zifman, Mark Hallett

Background: The utility of single-pulse TMS (transcranial magnetic stimulation)-evoked EEG (electroencephalograph) potentials (TEPs) has been extensively studied in the past three decades. TEPs have been shown to provide insights into features of cortical excitability and connectivity, reflecting mechanisms of excitatory/inhibitory balance, in various neurological and psychiatric conditions. In the present study, we sought to review and summarize the most studied neurological and psychiatric clinical indications utilizing single-pulse TEP and describe its promise as an informative novel tool for the evaluation of brain physiology. Methods: A thorough search of PubMed, Embase, and Google Scholar for original research utilizing single-pulse TMS-EEG and the measurement of TEP was conducted. Our review focused on the indications and outcomes most clinically relevant, commonly studied, and well-supported scientifically. Results: We included a total of 55 publications and summarized them by clinical application. We categorized these publications into seven sub-sections: healthy aging, Alzheimer's disease (AD), disorders of consciousness (DOCs), stroke rehabilitation and recovery, major depressive disorder (MDD), Parkinson's disease (PD), as well as prediction and monitoring of treatment response. Conclusions: TEP is a useful measurement of mechanisms underlying neuronal networks. It may be utilized in several clinical applications. Its most prominent uses include monitoring of consciousness levels in DOCs, monitoring and prediction of treatment response in MDD, and diagnosis of AD. Additional applications including the monitoring of stroke rehabilitation and recovery, as well as a diagnostic aid for PD, have also shown encouraging results but require further evidence from randomized controlled trials (RCTs).

背景:在过去的三十年里,人们对单脉冲 TMS(经颅磁刺激)诱发的脑电图电位(TEPs)的效用进行了广泛的研究。研究表明,TEPs 可以帮助人们深入了解大脑皮层的兴奋性和连通性特征,反映出各种神经和精神疾病的兴奋/抑制平衡机制。在本研究中,我们试图回顾和总结利用单脉冲 TEP 研究最多的神经和精神疾病临床适应症,并描述其作为评估大脑生理学的信息新工具的前景。研究方法在 PubMed、Embase 和 Google Scholar 上对利用单脉冲 TMS-EEG 和 TEP 测量的原始研究进行了全面搜索。我们的综述重点关注与临床最相关、研究最普遍、科学依据最充分的适应症和结果。结果:我们共收录了 55 篇出版物,并按临床应用进行了总结。我们将这些出版物分为七个小部分:健康老龄化、阿尔茨海默病 (AD)、意识障碍 (DOC)、中风康复和恢复、重度抑郁障碍 (MDD)、帕金森病 (PD),以及治疗反应的预测和监测。结论TEP 是对神经元网络基础机制的有效测量。它可用于多种临床应用。其最突出的用途包括监测 DOC 的意识水平、监测和预测 MDD 的治疗反应以及诊断 AD。其他应用包括监测中风康复和恢复,以及辅助诊断帕金森病,这些应用也取得了令人鼓舞的结果,但还需要随机对照试验(RCT)的进一步证明。
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引用次数: 0
Survival After Shunt Therapy in Normal-Pressure Hydrocephalus: A Meta-Analysis of 1614 Patients. 正常压力脑积水患者分流治疗后的存活率:对 1614 例患者的 Meta 分析。
IF 3.2 Q2 CLINICAL NEUROLOGY Pub Date : 2024-11-11 DOI: 10.3390/neurolint16060107
Johannes Wach, Agi Güresir, Erdem Güresir, Martin Vychopen

Background: Ventriculoperitoneal (VP) shunt therapy is a crucial intervention for normal-pressure hydrocephalus (NPH). This meta-analysis delves into survival time and the impact of baseline symptom burden on survival after VP shunt therapy for NPH, employing reconstructed pooled survival curves and a one-stage meta-analysis.

Methods: IPD regarding overall survival (OS) were acquired from published Kaplan-Meier charts, utilizing the R package IPDfromKM in R (Version 4.3.1, the R Foundation for Statistical Computing). Reconstructed Kaplan-Meier charts were then generated from the pooled IPD data. Both one-stage and two-stage meta-analyses were executed, with hazard ratios (HRs) employed as metrics to evaluate effectiveness.

Results: From the initial screening of 216 records, five articles encompassing 1614 patients met the eligibility criteria for inclusion. In two of the five included studies, overall survival was stratified by gait score (1-4 vs. ≥4) in 1043 patients, continence score (1-3 vs. ≥4) in 1022 patients, and mRS (0-2 vs. ≥3) in 956 patients. Patients with good gait demonstrated a mean survival of 8.24 years, while those with poor gait had a mean survival of 6.19 years (log-rank test: p < 0.001). The HR for gait was 2.25 (95% CI: 1.81-2.81, p < 0.001). Continence score stratification revealed a significant difference in survival time (log-rank test: p < 0.001), with an HR of 1.66 (95% CI: 1.33-2.06, p < 0.001). Similarly, mRS stratification demonstrated a significant survival difference (log-rank test: p < 0.001), with an HR of 2.21 (95% CI: 1. 74-2.80, p < 0.001). The reconstructed survival curves for all NPH patients treated with VP shunt therapy, pooling data from five studies, revealed a median survival time of 8.82 years (95% CI: 8.23-9.40). Survival rates at 1, 3, 5, 7, 9, 11, and 13 years were 95.7%, 83.8%, 70.5%, 59.5%, 48.7%, 35.8%, and 25.4%, respectively. Comparison with a general control population showed an HR of 1.79 (95% CI: 1.62-1.98, p < 0.001).

Conclusions: This comprehensive meta-analysis underscores the influence of baseline symptom burden on survival after VP shunt therapy in NPH. Therapy in the early stages for those without significant comorbidities may enhance survival.

背景:脑室腹腔(VP)分流疗法是治疗正常压力脑积水(NPH)的重要干预措施。这项荟萃分析采用重建的集合生存曲线和单阶段荟萃分析,探讨了正常压力脑积水 VP 分流治疗后的生存时间和基线症状负担对生存的影响:方法:利用R软件包IPDfromKM in R(4.3.1版,R Foundation for Statistical Computing)从已发表的Kaplan-Meier图表中获取有关总生存期(OS)的IPD。然后根据汇集的 IPD 数据生成重建的 Kaplan-Meier 图表。同时进行了单阶段和双阶段荟萃分析,并将危险比(HRs)作为评估疗效的指标:结果:在初步筛选的 216 条记录中,有五篇文章(涵盖 1614 名患者)符合纳入研究的资格标准。在纳入的五项研究中的两项研究中,根据步态评分(1-4分与≥4分)对1043名患者的总生存率进行了分层,根据失禁评分(1-3分与≥4分)对1022名患者的总生存率进行了分层,根据mRS(0-2分与≥3分)对956名患者的总生存率进行了分层。步态良好患者的平均生存期为 8.24 年,而步态不良患者的平均生存期为 6.19 年(对数秩检验:P < 0.001)。步态的 HR 为 2.25(95% CI:1.81-2.81,p < 0.001)。连续性评分分层显示生存时间存在显著差异(对数秩检验:P < 0.001),HR 为 1.66(95% CI:1.33-2.06,P < 0.001)。同样,mRS 分层也显示出显著的生存率差异(对数秩检验:P < 0.001),HR 为 2.21(95% CI:1.74-2.80,P < 0.001)。汇总五项研究的数据后,所有接受 VP 分流治疗的 NPH 患者的重建生存曲线显示,中位生存时间为 8.82 年(95% CI:8.23-9.40)。1、3、5、7、9、11 和 13 年的存活率分别为 95.7%、83.8%、70.5%、59.5%、48.7%、35.8% 和 25.4%。与普通对照人群相比,HR 为 1.79(95% CI:1.62-1.98,P <0.001):这项综合荟萃分析强调了基线症状负担对NPH患者VP分流治疗后存活率的影响。在早期阶段对无明显合并症的患者进行治疗可提高生存率。
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引用次数: 0
Evaluating the Usability of a Remote Ischemic Conditioning Device for Pre-Hospital Stroke Management: Insights from Paramedic Simulations. 评估用于院前中风管理的远程缺血调理设备的可用性:辅助医务人员模拟训练的启示。
IF 3.2 Q2 CLINICAL NEUROLOGY Pub Date : 2024-11-09 DOI: 10.3390/neurolint16060105
Bogna Anna Drozdowska, Kaden Lam, Cody Doolan, Efrem Violato, Aravind Ganesh

Background/objectives: In acute stroke, often-prolonged hospital transport times present an opportunity for early interventions to salvage brain tissue. Remote ischemic conditioning (RIC), where brief cycles of ischemia-reperfusion in a limb are induced to protect the brain, is a promising treatment for this setting. We assessed the usability of a novel RIC system in a simulated emergency response scenario.

Methods: Paramedics were asked to use the RIC device in an emergency stroke care and ambulance transport simulation, overseen by a confederate. Feedback on device use was collected through questionnaires, including the System Usability Scale (SUS) and the NASA Task Load Index (NASA-TLX), and a semi-structured interview. Questionnaire responses were summarized using descriptive statistics; interview transcripts were analyzed thematically.

Results: Nine paramedics (including the confederate) participated, with a mean of 10.0 ± 10.3 years of professional experience. Questionnaire responses indicated high device usability (mean SUS score: 85.3 ± 12.9 out of 100) and low task-related demands, effort, and frustration (mean NASA-TLX domain scores: ≤3.9 out of 20). Seven paramedics stated they would use the device in daily practice. They expressed concerns related to display screen clarity, interference with standard procedures, cable management, device fragility, and patient discomfort. Suggested improvements included adding indicators of device performance and refining the cuff design.

Conclusions: While the device was considered easy to use, paramedics also identified important areas of improvement. With a small, localized study sample, our findings are primarily applicable to the refinement of the RICovery system for use in future clinical trials in the same healthcare setting. However, feedback on the importance of mitigating potential interference of newly introduced procedures with those already established, robustness of equipment, and effective paramedic-patient communication may also help inform the design of other pre-hospital interventions.

背景/目的:在急性中风患者中,医院转运时间往往较长,这为早期干预抢救脑组织提供了机会。远程缺血调理(RIC)是在肢体中诱导短暂的缺血再灌注循环以保护大脑,是一种很有前景的治疗方法。我们在模拟急救场景中评估了新型 RIC 系统的可用性:方法:要求辅助医务人员在一名助手的监督下,在中风急救和救护车运送模拟场景中使用 RIC 设备。通过问卷调查(包括系统可用性量表(SUS)和 NASA 任务负荷指数(NASA-TLX))和半结构化访谈收集设备使用反馈。问卷回答采用描述性统计方法进行总结;访谈记录采用主题分析方法:九名护理人员(包括共事者)参加了调查,平均专业经验为 10.0 ± 10.3 年。问卷调查结果显示,设备可用性高(平均 SUS 得分:85.3 ± 12.9,满分 100 分),与任务相关的需求、努力和挫折感低(平均 NASA-TLX 领域得分:≤3.9,满分 20 分)。七名护理人员表示他们将在日常工作中使用该设备。他们对显示屏的清晰度、对标准程序的干扰、电缆管理、设备的易损性和病人的不适感表示担忧。改进建议包括增加设备性能指标和改进袖带设计:虽然该设备被认为易于使用,但护理人员也指出了需要改进的重要方面。由于研究样本较少且局限于本地,我们的研究结果主要适用于改进 RICovery 系统,以便在未来的临床试验中用于相同的医疗环境。然而,关于减少新引入程序对已确立程序的潜在干扰的重要性、设备的坚固性以及医护人员与患者之间的有效沟通等方面的反馈意见也有助于为其他院前干预措施的设计提供参考。
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引用次数: 0
Effectiveness and Feasibility of Blood Flow Restriction Training for People with Multiple Sclerosis: A Systematic Review. 多发性硬化症患者血流限制训练的有效性和可行性:系统回顾
IF 3.2 Q2 CLINICAL NEUROLOGY Pub Date : 2024-11-07 DOI: 10.3390/neurolint16060104
Aitor Blázquez-Fernández, Selena Marcos-Antón, Roberto Cano-de-la-Cuerda
<p><strong>Background: </strong>Multiple sclerosis (MS) is an immune-mediated inflammatory disease that primarily targets the myelin of axons. Extremities are frequently affected, resulting in a negative impact on both activities of daily living (ADL) and quality of life. In recent years, there has been increasing interest in the potential benefits of exercise and blood flow restriction training (BFRT) programs as a therapeutic tool in people with neurological disorders. The aim of the present systematic review was to know the clinical effects of BFRT programs in people with MS.</p><p><strong>Methods: </strong>A systematically comprehensive literature search was conducted and registered in PROSPERO prior to its execution under the reference number CRD42024588963. The following data sources were used: Pubmed, Scopus, Web of Science (WOS) and the Cochrane Library. The following data were extracted from the papers: study design, sample, interventions, dosage, outcome measures and results. To assess the methodological quality of the papers included, the Quality Index of Downs and Black was used. Additionally, the articles were classified according to the levels of evidence and grades of recommendation for diagnosis studies established by the Oxford Center for Evidence-Based Medicine. Also, the Cochrane Handbook for Systematic Reviews of Interventions was used by two independent reviewers to assess risk of bias, assessing the six different domains.</p><p><strong>Results: </strong>Seven articles with a total of 71 participants were included in the review. Of the seven articles, five papers studied the effectiveness of BFRT combined with strengthening exercises and two papers studied the effect of BFRT combined with aerobic exercise. Of the five articles that analyzed BFRT combined with strengthening exercises, only two presented a control group. Both performed a low-load resistance training in combination with BFRT with four series, 30/15/15/15 repetitions and a rest of 1 min between the series and 3 min between the exercises. The control groups to which they were compared performed a high intensity strengthening exercise protocol which had the same exercises, sets, rests and duration of the protocol as the experimental groups. For those two papers which investigated the effects of BFRT combined with aerobic training, exercise was performed in two sessions per week for a period of 8 and 6 weeks, respectively. In both studies, the experimental protocol began with a warm-up phase and ended with a cool-down phase, and there were differences in cuff management. All these investigations found positive effects in the interventions that combined exercise with BFRT. The characteristics, outcome measures, effects of the interventions and the assessment of the methodological quality of the included studies and risk of bias are shown in the tables.</p><p><strong>Conclusions: </strong>BFRT in people with MS appears to be effective and safe for people with MS. BFRT
背景:多发性硬化症(MS)是一种免疫介导的炎症性疾病,主要针对轴突的髓鞘。多发性硬化症患者的四肢经常受到影响,从而对日常生活活动(ADL)和生活质量造成负面影响。近年来,人们越来越关注运动和血流限制训练(BFRT)项目作为治疗工具对神经系统疾病患者的潜在益处。本系统综述旨在了解血流限制训练计划对多发性硬化症患者的临床效果:我们进行了系统全面的文献检索,并在执行前在 PROSPERO 中进行了注册,参考编号为 CRD42024588963。使用了以下数据源:Pubmed、Scopus、Web of Science (WOS) 和 Cochrane 图书馆。从论文中提取了以下数据:研究设计、样本、干预措施、剂量、结果测量和结果。为了评估所收录论文的方法学质量,采用了唐斯和布莱克的质量指数。此外,还根据牛津循证医学中心(Oxford Center for Evidence-Based Medicine)为诊断研究制定的证据等级和推荐等级对文章进行了分类。此外,两位独立审稿人还使用了《科克伦干预措施系统综述手册》来评估偏倚风险,并对六个不同的领域进行了评估:结果:共有七篇文章、71 名参与者参与了此次综述。在这 7 篇文章中,有 5 篇研究了 BFRT 与强化运动相结合的效果,有 2 篇研究了 BFRT 与有氧运动相结合的效果。在分析阻力训练与强化训练相结合的五篇文章中,只有两篇文章提出了对照组。这两篇文章都在进行低负荷阻力训练的同时结合了 BFRT,训练分为四个系列,重复次数为 30/15/15/15,每个系列之间休息 1 分钟,每个练习之间休息 3 分钟。与实验组进行比较的对照组则进行了高强度强化训练,其练习、组数、休息时间和持续时间与实验组相同。有两篇论文对 BFRT 与有氧训练相结合的效果进行了研究,这两篇论文中的运动分别持续了 8 周和 6 周,每周两次。在这两项研究中,实验方案均以热身阶段开始,以冷却阶段结束,袖带管理也有所不同。所有这些研究都发现,结合运动和 BFRT 的干预措施具有积极的效果。表中显示了纳入研究的特点、结果测量、干预效果以及方法学质量评估和偏倚风险:在多发性硬化症患者中进行 BFRT 似乎对多发性硬化症患者有效且安全。BFRT可能会对力量、肥大和平衡结果产生积极的临床影响。然而,由于所分析的研究存在较高的偏倚风险和方法学局限性,未来的研究应采用质量更高的方法,以确保BFRT对多发性硬化症患者的潜在益处。
{"title":"Effectiveness and Feasibility of Blood Flow Restriction Training for People with Multiple Sclerosis: A Systematic Review.","authors":"Aitor Blázquez-Fernández, Selena Marcos-Antón, Roberto Cano-de-la-Cuerda","doi":"10.3390/neurolint16060104","DOIUrl":"https://doi.org/10.3390/neurolint16060104","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Multiple sclerosis (MS) is an immune-mediated inflammatory disease that primarily targets the myelin of axons. Extremities are frequently affected, resulting in a negative impact on both activities of daily living (ADL) and quality of life. In recent years, there has been increasing interest in the potential benefits of exercise and blood flow restriction training (BFRT) programs as a therapeutic tool in people with neurological disorders. The aim of the present systematic review was to know the clinical effects of BFRT programs in people with MS.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A systematically comprehensive literature search was conducted and registered in PROSPERO prior to its execution under the reference number CRD42024588963. The following data sources were used: Pubmed, Scopus, Web of Science (WOS) and the Cochrane Library. The following data were extracted from the papers: study design, sample, interventions, dosage, outcome measures and results. To assess the methodological quality of the papers included, the Quality Index of Downs and Black was used. Additionally, the articles were classified according to the levels of evidence and grades of recommendation for diagnosis studies established by the Oxford Center for Evidence-Based Medicine. Also, the Cochrane Handbook for Systematic Reviews of Interventions was used by two independent reviewers to assess risk of bias, assessing the six different domains.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Seven articles with a total of 71 participants were included in the review. Of the seven articles, five papers studied the effectiveness of BFRT combined with strengthening exercises and two papers studied the effect of BFRT combined with aerobic exercise. Of the five articles that analyzed BFRT combined with strengthening exercises, only two presented a control group. Both performed a low-load resistance training in combination with BFRT with four series, 30/15/15/15 repetitions and a rest of 1 min between the series and 3 min between the exercises. The control groups to which they were compared performed a high intensity strengthening exercise protocol which had the same exercises, sets, rests and duration of the protocol as the experimental groups. For those two papers which investigated the effects of BFRT combined with aerobic training, exercise was performed in two sessions per week for a period of 8 and 6 weeks, respectively. In both studies, the experimental protocol began with a warm-up phase and ended with a cool-down phase, and there were differences in cuff management. All these investigations found positive effects in the interventions that combined exercise with BFRT. The characteristics, outcome measures, effects of the interventions and the assessment of the methodological quality of the included studies and risk of bias are shown in the tables.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;BFRT in people with MS appears to be effective and safe for people with MS. BFRT","PeriodicalId":19130,"journal":{"name":"Neurology International","volume":"16 6","pages":"1385-1404"},"PeriodicalIF":3.2,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Differential Effects of Extracellular Vesicles from Two Different Glioblastomas on Normal Human Brain Cells. 两种不同胶质母细胞瘤的细胞外小泡对正常人脑细胞的不同影响
IF 3.2 Q2 CLINICAL NEUROLOGY Pub Date : 2024-11-06 DOI: 10.3390/neurolint16060103
Mary Wang, Arin N Graner, Bryne Knowles, Charlotte McRae, Anthony Fringuello, Petr Paucek, Michael Gavrilovic, McKenna Redwine, Caleb Hanson, Christina Coughlan, Stacey Grimaldo-Garcia, Brooke Metzger, Vince Bolus, Timothy J Kopper, Marie Smith, Wenbo Zhou, Morgan Lenz, Aviva Abosch, Steven Ojemann, Kevin O Lillehei, Xiaoli Yu, Michael W Graner

Background/Objectives: Glioblastomas (GBMs) are dreadful brain tumors with abysmal survival outcomes. GBM extracellular vesicles (EVs) dramatically affect normal brain cells (largely astrocytes) constituting the tumor microenvironment (TME). We asked if EVs from different GBM patient-derived spheroid lines would differentially alter recipient brain cell phenotypes. This turned out to be the case, with the net outcome of treatment with GBM EVs nonetheless converging on increased tumorigenicity. Methods: GBM spheroids and brain slices were derived from neurosurgical patient tissues following informed consent. Astrocytes were commercially obtained. EVs were isolated from conditioned culture media by ultrafiltration, concentration, and ultracentrifugation. EVs were characterized by nanoparticle tracking analysis, electron microscopy, biochemical markers, and proteomics. Astrocytes/brain tissues were treated with GBM EVs before downstream analyses. Results: EVs from different GBMs induced brain cells to alter secretomes with pro-inflammatory or TME-modifying (proteolytic) effects. Astrocyte responses ranged from anti-viral gene/protein expression and cytokine release to altered extracellular signal-regulated protein kinase (ERK1/2) signaling pathways, and conditioned media from EV-treated cells increased GBM cell proliferation. Conclusions: Astrocytes/brain slices treated with different GBM EVs underwent non-identical changes in various omics readouts and other assays, indicating "personalized" tumor-specific GBM EV effects on the TME. This raises concern regarding reliance on "model" systems as a sole basis for translational direction. Nonetheless, net downstream impacts from differential cellular and TME effects still led to increased tumorigenic capacities for the different GBMs.

背景/目标:胶质母细胞瘤(GBM)是一种可怕的脑肿瘤,存活率极低。GBM 细胞外囊泡(EVs)会显著影响构成肿瘤微环境(TME)的正常脑细胞(主要是星形胶质细胞)。我们询问来自不同 GBM 患者衍生球状细胞系的 EV 是否会不同程度地改变受体脑细胞表型。事实证明确实如此,用 GBM EVs 治疗的净结果还是趋向于增加致瘤性。方法GBM 球形细胞和脑切片来自神经外科患者的知情同意组织。星形胶质细胞通过商业途径获得。通过超滤、浓缩和超速离心从条件培养基中分离出 EVs。通过纳米粒子跟踪分析、电子显微镜、生化标记和蛋白质组学对 EVs 进行表征。在进行下游分析之前,用 GBM EVs 处理星形胶质细胞/脑组织。结果来自不同GBM的EV诱导脑细胞改变具有促炎或TME修饰(蛋白水解)作用的分泌物组。星形胶质细胞的反应包括抗病毒基因/蛋白表达和细胞因子释放,以及细胞外信号调节蛋白激酶(ERK1/2)信号通路的改变。结论经不同 GBM EV 处理的星形胶质细胞/脑片在各种全息图读数和其他检测中发生了不相同的变化,这表明肿瘤特异性 GBM EV 对 TME 的影响是 "个性化 "的。这引起了人们对依赖 "模型 "系统作为转化方向唯一依据的担忧。尽管如此,不同细胞和肿瘤组织生长因子效应的净下游影响仍然导致不同 GBM 的致瘤能力增加。
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引用次数: 0
Painful Legs and Moving Toes Syndrome: Case Report and Review. 腿痛和脚趾移动综合征:病例报告与回顾
IF 3.2 Q2 CLINICAL NEUROLOGY Pub Date : 2024-11-04 DOI: 10.3390/neurolint16060102
Mihael Tsalta-Mladenov, Vladina Dimitrova, Silva Andonova

Introduction: Painful legs and moving toes (PLMT) syndrome is a rare movement disorder characterized by defuse lower limb neuropathic pain and spontaneous abnormal, involuntary toe movements.

Objective: The objective was to present a rare case of PLMT syndrome with a triggering area in an adult patient due to multilevel discogenic pathology, to make a thorough review of this disorder and to provide a practical approach to its management.

Case presentation: A 59-years-old male was admitted to the neurology ward with symptoms of defuse pain in the lower-back and the right leg accompanied by involuntary movements for the right toes intensified by tactile stimulation in the right upper thigh. Magnetic resonance imaging (MRI) revealed a multilevel discogenic pathology of the lumbar and cervical spine, with myelopathy at C5-C7 level. A medication with Pregabalin 300 mg/daily significantly improved both the abnormal toe movements and the leg pain. The clinical effect was constant during the 90-day follow-up without any adverse effects.

Conclusion: Painful legs and moving toes (PLMT) is a condition that greatly affects the quality of life of patients, but which still remains less known by clinicians. Spontaneous resolution is rare, and oral medications are the first-line treatment. Pregabalin is a safe and effective treatment option for PLMT that should be considered early for the management of this condition. Other medication interventions, such as botulinum toxin injections, spinal blockade, or non-pharmacological treatment options like spinal cord stimulation, and surgical decompressions, are also recommended when the conservative treatment is ineffective in well-selected patients.

简介:疼痛性腿和脚趾运动综合征(PLMT)是一种罕见的运动障碍疾病,其特征是下肢神经病理性疼痛缓解和自发性异常不自主脚趾运动:疼痛性腿和脚趾运动综合征(PLMT)是一种罕见的运动障碍,其特征是下肢神经病理性疼痛和自发性异常、不自主脚趾运动:目的:介绍一例罕见的成年患者因多层次椎间盘病变导致的具有触发区的 PLMT 综合征,对该疾病进行全面回顾,并提供实用的治疗方法:一名 59 岁的男性因下腰和右腿疼痛加剧,伴有右脚趾不自主运动,右大腿上部触觉刺激加剧的症状被送入神经内科病房。磁共振成像(MRI)显示,腰椎和颈椎存在多级椎间盘病变,C5-C7水平存在脊髓病变。服用普瑞巴林 300 毫克/天的药物后,脚趾异常运动和腿部疼痛都得到了明显改善。临床效果在90天的随访中保持不变,且无任何不良反应:结论:腿痛和脚趾移动(PLMT)是一种严重影响患者生活质量的疾病,但临床医生对这种疾病的了解仍然较少。自发缓解的情况很少见,口服药物是一线治疗方法。普瑞巴林是一种安全有效的 PLMT 治疗选择,应尽早考虑用于治疗这种疾病。当保守治疗无效时,也建议对经过严格筛选的患者采取其他药物干预措施,如注射肉毒杆菌毒素、脊髓阻滞或脊髓刺激、手术减压等非药物治疗方案。
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引用次数: 0
The Role of Neuropeptide Y in the Pathogenesis of Alzheimer's Disease: Diagnostic Significance and Neuroprotective Functions. 神经肽 Y 在阿尔茨海默病发病机制中的作用:诊断意义和神经保护功能。
IF 3.2 Q2 CLINICAL NEUROLOGY Pub Date : 2024-11-01 DOI: 10.3390/neurolint16060100
Ksenia Shapovalova, Yana Zorkina, Olga Abramova, Alisa Andryushchenko, Vladimir Chekhonin, Georgy Kostyuk

Background. Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. It has been suggested that the factors that cause pathologic changes and lead to the development of AD may also include changes in certain neuropeptides. The implication of the neuropeptide (NPY) in the pathogenesis of AD and its potential therapeutic role is possible due to the following properties: involvement in adult neurogenesis, regulatory effects on the immune system, the inhibition of potential-dependent Ca2+ channels, and the reduction in glutamate excitotoxicity. The aim of our review was to summarize recent data on the role of NPY in AD development and to explore its potential as a biomarker and a possible therapeutic target. Materials and methods. We performed a systematic review of studies, for which we search using the keywords "Alzheimer's disease and neuropeptide Y", "Alzheimer's disease and NPY", "AD and NPY", "Neuropeptide Y and Neurodegenerative disease". Nineteen articles were included in the review. Results. The NPY levels in cerebrospinal fluid and plasma have been found to be reduced or unchanged in AD patients; however, these findings need to be confirmed in more recent studies. Data obtained in transgenic animal models support the role of NPY in AD pathogenesis. The neuroprotective effects of NPY have been demonstrated in vitro and in vivo in AD models. Conclusion. The findings may open new possibilities for using NPY as a diagnostic marker to detect AD at earlier stages of the disease or as a potential therapeutic target due to its neuroprotective properties.

背景。阿尔茨海默病(AD)是最常见的神经退行性疾病之一。有研究认为,引起病理变化并导致阿尔茨海默病发病的因素可能还包括某些神经肽的变化。神经肽(NPY)具有以下特性,可能与 AD 的发病机制有关,并具有潜在的治疗作用:参与成人神经发生、对免疫系统的调节作用、抑制电位依赖性 Ca2+ 通道以及降低谷氨酸兴奋毒性。我们的综述旨在总结有关 NPY 在老年痴呆症发展过程中的作用的最新数据,并探讨其作为生物标志物和可能的治疗靶点的潜力。材料和方法。我们使用关键词 "阿尔茨海默病与神经肽 Y"、"阿尔茨海默病与 NPY"、"AD 与 NPY"、"神经肽 Y 与神经退行性疾病 "对相关研究进行了系统性综述。19篇文章被纳入综述。结果。研究发现,AD 患者脑脊液和血浆中的 NPY 水平降低或保持不变;然而,这些发现还需要更多最新研究的证实。转基因动物模型获得的数据支持 NPY 在 AD 发病机制中的作用。NPY 的神经保护作用已在 AD 模型的体外和体内得到证实。结论。这些发现为将 NPY 用作诊断标记物以在疾病早期阶段检测出 AD 或因其神经保护特性而将其用作潜在治疗靶点提供了新的可能性。
{"title":"The Role of Neuropeptide Y in the Pathogenesis of Alzheimer's Disease: Diagnostic Significance and Neuroprotective Functions.","authors":"Ksenia Shapovalova, Yana Zorkina, Olga Abramova, Alisa Andryushchenko, Vladimir Chekhonin, Georgy Kostyuk","doi":"10.3390/neurolint16060100","DOIUrl":"https://doi.org/10.3390/neurolint16060100","url":null,"abstract":"<p><p><b>Background</b>. Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. It has been suggested that the factors that cause pathologic changes and lead to the development of AD may also include changes in certain neuropeptides. The implication of the neuropeptide (NPY) in the pathogenesis of AD and its potential therapeutic role is possible due to the following properties: involvement in adult neurogenesis, regulatory effects on the immune system, the inhibition of potential-dependent Ca<sup>2+</sup> channels, and the reduction in glutamate excitotoxicity. The aim of our review was to summarize recent data on the role of NPY in AD development and to explore its potential as a biomarker and a possible therapeutic target. <b>Materials and methods</b>. We performed a systematic review of studies, for which we search using the keywords \"Alzheimer's disease and neuropeptide Y\", \"Alzheimer's disease and NPY\", \"AD and NPY\", \"Neuropeptide Y and Neurodegenerative disease\". Nineteen articles were included in the review. <b>Results</b>. The NPY levels in cerebrospinal fluid and plasma have been found to be reduced or unchanged in AD patients; however, these findings need to be confirmed in more recent studies. Data obtained in transgenic animal models support the role of NPY in AD pathogenesis. The neuroprotective effects of NPY have been demonstrated in vitro and in vivo in AD models. <b>Conclusion</b>. The findings may open new possibilities for using NPY as a diagnostic marker to detect AD at earlier stages of the disease or as a potential therapeutic target due to its neuroprotective properties.</p>","PeriodicalId":19130,"journal":{"name":"Neurology International","volume":"16 6","pages":"1318-1331"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effects of Respiratory Training on Pulmonary Function, Cough, and Functional Independence in Patients with Amyotrophic Lateral Sclerosis. 呼吸训练对肌萎缩侧索硬化症患者肺功能、咳嗽和功能独立性的影响
IF 3.2 Q2 CLINICAL NEUROLOGY Pub Date : 2024-11-01 DOI: 10.3390/neurolint16060101
Eleonora Magni, Anja Hochsprung, Rocío Cáceres-Matos, Manuel Pabón-Carrasco, Beatriz Heredia-Camacho, Ignacio Solís-Marcos, Carlos Luque-Moreno

Background: Respiratory complications in patients with amyotrophic lateral sclerosis (ALS), due to the involvement of respiratory muscles, are the leading cause of death, and respiratory physiotherapy (RP) focuses on addressing these complications.

Objectives: The objective was to evaluate the effectiveness of an RP intervention that combines the four specific techniques (inspiratory muscle training, lung volume recruitment, manually assisted coughing, and diaphragmatic breathing training) in patients with ALS.

Methods: A quasi-experimental study was carried out, and a specific RP programme was implemented in 15 patients with ALS (12 sessions, 30 min/session, one session/week, duration of three months), based on directed ventilation techniques, lung volume recruitment, manually assisted coughing, and the use of incentive spirometry and a cough assist device, along with a daily home exercise programme. Respiratory functions were assessed (pre- and post-intervention, with follow-up at three months) using Forced Vital Capacity (FVC) and Peak Expiratory Cough Flow (PECF); functionality was assessed using the Revised ALS Functional Rating Scale (ALSFRS-R) and the Modified Barthel Index by Granger.

Results: FVC experienced an increase after three months of the intervention initiation (p = 0.30), which was not sustained at the three-month follow-up after the intervention ended. All other variables remained practically constant after treatment, with their values decreasing at follow-up.

Conclusion: A specific RP intervention could have beneficial effects on respiratory functions, potentially preventing pulmonary infections and hospitalisations in patients with ALS. It may improve FVC and help stabilize the patient's functional decline. Considering the progressive and degenerative nature of the disease, this finding could support the usefulness of these techniques in maintaining respiratory function.

背景:肌萎缩性脊髓侧索硬化症(ALS)患者因呼吸肌受累引起的呼吸系统并发症是死亡的主要原因,而呼吸物理治疗(RP)的重点就是解决这些并发症:目的:评估结合四种特定技术(吸气肌训练、肺容量募集、人工辅助咳嗽和横膈膜呼吸训练)的呼吸理疗干预对 ALS 患者的效果:开展了一项准实验研究,对 15 名 ALS 患者实施了一项特定的 RP 计划(12 次课,每次课 30 分钟,每周一次课,为期三个月),该计划以定向通气技术、肺容积募集、人工辅助咳嗽、激励肺活量测定和咳嗽辅助装置的使用为基础,并配合日常家庭锻炼计划。使用强制生命容量(FVC)和呼气咳嗽峰值流量(PECF)评估呼吸功能(干预前和干预后,随访三个月);使用修订版 ALS 功能评定量表(ALSFRS-R)和格兰杰改良巴特尔指数评估功能:结果:干预开始三个月后,肺活量增加(p = 0.30),但在干预结束后的三个月随访中,肺活量并未持续增加。所有其他变量在治疗后基本保持不变,其数值在随访时有所下降:结论:特定的 RP 干预可对 ALS 患者的呼吸功能产生有益影响,并有可能预防肺部感染和住院治疗。它可以改善肺活量(FVC),有助于稳定患者的功能衰退。考虑到该疾病的渐进性和退行性,这一发现可能会支持这些技术在维持呼吸功能方面的作用。
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引用次数: 0
Cyproheptadine Treatment in Children and Adolescents with Migraine: A Retrospective Study in Japan. 儿童和青少年偏头痛患者的赛庚啶治疗:日本的一项回顾性研究
IF 3.2 Q2 CLINICAL NEUROLOGY Pub Date : 2024-10-30 DOI: 10.3390/neurolint16060099
Hideki Shimomura, Sachi Tokunaga, Eisuke Terasaki, Naoko Taniguchi, Yohei Taniguchi, Saeka Yoshitake, Yuki Terakita, Kenji Inoue, Masumi Okuda, Takeo Kato, Yasuhiro Takeshima

Objective: Evidence on prophylactic drugs for pediatric migraine is limited, especially when comorbid conditions contribute to treatment resistance. This study evaluated the efficacy of cyproheptadine in children with migraine and explored the impact of comorbid neurodevelopmental disorders and orthostatic intolerance (OI).

Methods: We retrospectively analyzed pediatric migraine patients treated with cyproheptadine. Efficacy was assessed based on the reduction in headache frequency, with responders defined as patients experiencing at least a 50% reduction in headache episodes. Fisher's exact test analyzed the relationship between efficacy and comorbid conditions or treatment sequence. Multiple logistic regression was performed to identify factors associated with adverse events.

Results: In total, 155 children (71 males, 84 females) aged 3-15 years were included. Comorbid neurodevelopmental disorders and OI were present in 27 (17.4%) and 22 (14.2%) patients, respectively. Efficacy was evaluated in 148 patients, with 68.9% classified as responders. Patients with comorbid conditions showed lower efficacy. Responders required a lower dose of cyproheptadine (p = 0.039). Multiple logistic regression identified headache frequency, cyproheptadine dose, and comorbid OI and neurodevelopmental disorders as factors influencing treatment efficacy.

Conclusions: Cyproheptadine is effective in treating pediatric migraine, though patients with neurodevelopmental disorders and OI demonstrated reduced efficacy.

目的:有关小儿偏头痛预防性药物的证据有限,尤其是当合并症导致治疗抵抗时。本研究评估了环丙沙星在儿童偏头痛患者中的疗效,并探讨了合并神经发育障碍和正压性不耐受(OI)的影响:我们对接受环丙沙星治疗的儿童偏头痛患者进行了回顾性分析。疗效根据头痛次数的减少情况进行评估,头痛发作次数至少减少 50%的患者即为应答者。费雪精确检验分析了疗效与合并症或治疗顺序之间的关系。为确定与不良事件相关的因素,进行了多元逻辑回归:共纳入 155 名 3-15 岁儿童(71 名男性,84 名女性)。分别有27名(17.4%)和22名(14.2%)患者合并神经发育障碍和OI。对 148 名患者进行了疗效评估,68.9% 的患者被列为应答者。合并症患者的疗效较低。应答者所需的环丙沙星剂量较低(p = 0.039)。多元逻辑回归确定头痛频率、环丙氯雷定剂量、合并OI和神经发育障碍是影响疗效的因素:结论:环丙雷他定对治疗小儿偏头痛有效,但对患有神经发育障碍和OI的患者疗效较差。
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引用次数: 0
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Neurology International
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