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Changes in contractile characteristics of rat skeletal muscles associated with P2-receptor activation after spinal cord transection 脊髓横断后与 P2 受体激活相关的大鼠骨骼肌收缩特性的变化
Q3 Multidisciplinary Pub Date : 2024-07-08 DOI: 10.17816/acen.1012
A. E. Khairullin, D. V. Efimova, M. A. Mukhamedyarov, M. Baltin, T. Baltina, S. Grishin, A. Ziganshin
Introduction. Traumatic spinal cord and peripheral-nerve injury is associated with release of proinflammatory cytokines and chemokines, which may stimulate neuronal activity. Adenosine triphosphoric acid (ATP) is an important pain mediator involved in the acute and chronic neuropathic pain development. Its excessive release from primary injured tissue leads to activation of P2-receptors, which may further start secondary injury mechanisms. Although the effects of ATP on the peripheral nervous system are relatively well studied, the pathophysiological role of purinergic signaling after spinalization remains unclear. The study was aimed at assessing the post-spinalization effects of P2-receptors on the contractile characteristics of rat skeleton muscles. Materials and methods. The objects of the study were the soleus muscle, the extensor digitorum longus (EDL) muscle, and diaphragm in intact rats and spinalized rats. Seven days after laminectomy followed by spinal cord transection, animals were anesthetized, exsanguinated, and their muscles with nerve stumps were isolated. Contractile response parameters were recorded using mechanomyography (MMG). To study effects of ATP on ligand binding, ATP was added to a bath and mechanical responses in the rat muscles were assessed 7 min after. After washing with Krebs–Henseleit solution, the preparations were incubated with suramin solution for 20 min with subsequent ATP application. Then the mechanical responses in the muscles were again recorded. Statistical significance was assessed using Student's t-test for independent (unpaired) and paired samples. Results. We found a significant (p 0.05) decrease in the modulating activity of ATP, as the main endogenous signaling agent, in the cholinergic synapse of the soleus muscle from 32.4 to 5.8% and from 13.7 to 5.6% for the EDL muscle after the spinalization (spinal cord injury at the Th6–Th7 level) compared with intact animals. No such dramatic changes were observed in the diaphragm. Conclusions. Abnormal ATP-mediated modulation of neuromuscular transmission demonstrated in this study supports the involvement of purinergic signaling in the neurotrophic control and functioning of various motor units.
简介创伤性脊髓和外周神经损伤与促炎细胞因子和趋化因子的释放有关,这些因子可刺激神经元活动。三磷酸腺苷(ATP)是一种重要的疼痛介质,参与急性和慢性神经病理性疼痛的发展。它从原发性损伤组织中过度释放,导致 P2 受体被激活,从而可能进一步启动继发性损伤机制。虽然 ATP 对周围神经系统的影响研究相对较多,但脊髓化后嘌呤能信号的病理生理作用仍不清楚。本研究旨在评估脊髓化后 P2 受体对大鼠骨骼肌收缩特性的影响。材料和方法。研究对象是完整大鼠和脊髓化大鼠的比目鱼肌、伸肌和膈肌。在椎板切除术和脊髓横断术后七天,对动物进行麻醉、放血,并分离带神经残端的肌肉。使用机械肌电图(MMG)记录收缩反应参数。为了研究 ATP 对配体结合的影响,将 ATP 加入水浴中,7 分钟后评估大鼠肌肉的机械反应。用克雷布斯-亨斯莱特溶液清洗后,将制备物与苏拉明溶液孵育 20 分钟,随后加入 ATP。然后再次记录肌肉的机械反应。采用学生 t 检验法对独立样本(非配对)和配对样本进行统计意义评估。结果我们发现,与完整动物相比,脊髓化(Th6-Th7水平脊髓损伤)后比目鱼肌胆碱能突触中作为主要内源性信号物质的 ATP 的调节活性明显降低(p 0.05),从 32.4% 降至 5.8%,EDL 肌从 13.7% 降至 5.6%。在膈肌中没有观察到如此显著的变化。结论本研究证明 ATP 介导的神经肌肉传导调节异常支持嘌呤能信号参与各种运动单元的神经营养控制和功能。
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引用次数: 0
Surgical Treatment Options for Degenerative Lumbosacral Spinal Stenosis 退行性腰骶椎管狭窄症的手术治疗方案
Q3 Multidisciplinary Pub Date : 2024-04-05 DOI: 10.54101/acen.2024.1.9
Adilya R. Yusupova, A. Gushcha, S. Arestov, D. Petrosyan, R. Kartavykh, A. Simonyan, Andrey A. Kiselev
Degenerative spinal stenosis is the most common type of degenerative and dystrophic spine disease. The clinical picture of stenosis, which may include axial pain syndrome, leg pain, intermittent claudication syndrome, weakness and loss of sensitivity in the legs, and impaired pelvic functions, can significantly worsen patients’ quality of life and reduce their ability to work and lead an active lifestyle. Degenerative spinal stenosis mostly affects the elderly. Therapeutic and neurological communities have stereotypes about spine surgery being too traumatic and invasive, and, therefore, they believe that their use should be contraindicated to and limited in elderly patients. However, surgeons are increasingly giving preference to minimally invasive interventions with high efficacy and safety together with a low risk of complications. We aimed at reviewing current treatment methods for degenerative lumbosacral spinal stenosis with an emphasis on surgical treatment methods.
退行性椎管狭窄症是最常见的退行性和萎缩性脊柱疾病。椎管狭窄症的临床表现可能包括轴性疼痛综合征、腿痛、间歇性跛行综合征、腿部无力和失去知觉、骨盆功能受损等,会严重恶化患者的生活质量,降低其工作和积极生活的能力。退行性椎管狭窄症主要影响老年人。治疗界和神经病学界对脊柱手术的刻板印象是创伤性和侵入性太大,因此认为老年患者应禁忌和限制使用脊柱手术。然而,外科医生越来越倾向于采用疗效好、安全性高、并发症风险低的微创介入疗法。我们旨在回顾目前治疗退行性腰骶椎管狭窄症的方法,重点是手术治疗方法。
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引用次数: 0
Changes in Clinical and Network Functional Connectivity Parameters in Motor Networks and Cerebellum Based on Resting-State Functional Magnetic Resonance Imaging Data in Patients with Post-Stroke Hemiparesis Receiving Interactive Brain Stimulation Neurotherapy 基于静息态功能磁共振成像数据的脑卒中后偏瘫患者接受交互式脑刺激神经疗法后运动网络和小脑的临床和网络功能连接参数的变化
Q3 Multidisciplinary Pub Date : 2024-04-05 DOI: 10.54101/acen.2024.1.4
Nadezhda A. Khrushcheva, K. Kalgin, Andrey A. Savelov, A. V. Shurunova, E. V. Predtechenskaya, M. Shtark
Introduction. Interactive brain stimulation (IBS) neurotherapy is an advanced neurofeedback technology (NFB) that involves the organization of a feedback “target” based on signals recorded by functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). The NFB allows patients to volitionally self-regulate their current brain activity and may therefore be a useful treatment option for diseases with altered activation and functional connectivity (FC) patterns. Our objective was to assess the effects of IBS on the FC changes in motor networks and correlations between clinical and network parameters in patients with post-stroke hand paresis. Materials and methods. Patients with a history of stroke 2 months were randomized into a main group (n = 7) and a control group (n = 7). All the patients followed the stroke physical rehabilitation for 3 weeks. The main group received IBS training, where the patients learned to imagine movements of the paretic hand trying to amplify the fMRI signal from the primary motor cortex (M1) and the supplementary motor area (SMA) on the lesion side with simultaneous desynchronizing the μ- and β-2 EEG rhythms in the central leads. Clinical tests and MRI were performed prior to and immediately after the treatment. FC matrices were constructed using CONN software based on resting-state fMRI data. Results. By the end of the training, M1–M1 functional connectivity in the control group weakened, while no changes were observed in the main group. The FC strength was positively correlated with the grip strength (ρ = 0.69; p 0.01) and with the results of the Box and Blocks test (BBT score, ρ = 0.72; p 0.01) and the Fugl-Meyer assessment for upper extremity (FM-UE score, ρ = 0.87; p 0.005). Ipsilesional SMA connectivity with contralesional cerebellum weakened (p 0.05 in the main group). Its strength was negatively correlated with the BBT and FM-UE scores (both tests ρ = –0.44; p 0.05). Conclusions. Volitional control of M1 and SMA activity in the lesion hemisphere during the post-stroke IBS training alters the architecture of the entire motor network affecting clinically significant FC types. We studied a possible mechanism of this technology and its potential use in treatment programs.
简介交互式脑刺激(IBS)神经疗法是一种先进的神经反馈技术(NFB),它根据功能性磁共振成像(fMRI)和脑电图(EEG)记录的信号组织反馈 "目标"。NFB 允许患者自愿地自我调节当前的大脑活动,因此可能是治疗激活和功能连接(FC)模式改变的疾病的有效方法。我们的目的是评估 IBS 对中风后手部瘫痪患者运动网络 FC 变化的影响,以及临床参数和网络参数之间的相关性。材料与方法将有中风病史 2 个月的患者随机分为主要组(n = 7)和对照组(n = 7)。所有患者均接受为期 3 周的中风物理康复训练。主组接受 IBS 训练,患者学会想象瘫痪手的动作,尝试放大病变侧初级运动皮层(M1)和辅助运动区(SMA)的 fMRI 信号,同时使中央导联的μ-和β-2 EEG 节律不同步。治疗前后均进行了临床测试和磁共振成像。根据静息态 fMRI 数据,使用 CONN 软件构建 FC 矩阵。结果显示训练结束后,对照组的 M1-M1 功能连通性减弱,而主要组则未观察到任何变化。功能连接强度与握力(ρ = 0.69; p 0.01)、方框和块测试结果(BBT 分数,ρ = 0.72; p 0.01)和 Fugl-Meyer 上肢评估(FM-UE 分数,ρ = 0.87; p 0.005)呈正相关。SMA与对侧小脑的连接减弱(主要组中 p 0.05)。其强度与 BBT 和 FM-UE 评分呈负相关(两项测试的 ρ = -0.44; p 0.05)。结论在脑卒中后 IBS 训练中,对病变半球 M1 和 SMA 活动的意志控制改变了整个运动网络的结构,影响了具有临床意义的 FC 类型。我们研究了这项技术的可能机制及其在治疗计划中的潜在用途。
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引用次数: 0
Efficacy and Safety of PEGylated Interferons for Relapsing-Remitting Multiple Sclerosis in Adult Patients: Results of Matching-Adjusted Indirect Comparison PEG 化干扰素治疗成人复发性多发性硬化症的疗效和安全性:匹配调整间接比较的结果
Q3 Multidisciplinary Pub Date : 2024-04-05 DOI: 10.54101/acen.2024.1.5
T. Simaniv, M. Zakharova, K. V. Sapozhnikov, D. Tolkacheva, Valeriia D. Sokolova, N. Sableva, O. Mironenko, Taras V. Khimich
Introduction. Beta interferons are effective and safe agents for the treatment of relapsing-remitting multiple sclerosis (RRMS). PEGylated interferons have been developed in order to increase patient adherence. Direct comparisons of the efficacy and safety of PEGylated interferons have not yet been conducted. Our objective was to evaluate the efficacy and safety of SamPEG-IFN-β1a versus PEG-IFN-β1a in adult patients with RRMS. Materials and methods. We conducted a systematic search of randomized clinical trials (RCTs) using the PubMed, Embase and eLIBRARY.RU databases. Efficacy was assessed based on the proportion of patients with disease relapses and the annualized relapse rate (ARR) during the 1st and the 2nd years of treatment. Safety was assessed by the number of patients with adverse events (AEs), serious AEs (SAEs), and any AEs that led to the treatment discontinuation. We conducted pairwise matching-adjusted indirect comparison (MAIC) to assess comparative efficacy of PEGylated IFNs. To evaluate the efficacy, hypotheses of non-inferiority of SamPEG-IFN-β1a to PEG-IFN-β1a and superiority of SamPEG-IFN-β1a over PEG-IFN-β1a were tested. Results. Based on results of the systematic review, four articles were selected wherein the results of phase 3 clinical trial of PEG-IFN-β1a and phase 2–3 clinical trial of SamPEG-IFN-β1a were described. In PEG-IFN-β1a group (n = 512) the agent was administered once every 2 weeks, in SamPEGIFN-β1a group (n = 114) the agent was administered at a dose of 240 μg. The analysis results confirmed the hypothesis of SamPEG-IFN-β1a non-inferiority to PEG-IFN-β1a in efficacy, while SamPEG-IFN-β1a superiority over PEG-IFN-β1a in efficacy was not confirmed. The hypothesis of SamPEG-IFN-β1a superiority over PEG-IFN-β1a in safety was also confirmed based on a significantly lower incidence of SAEs and any AEs that led to treatment discontinuation. Conclusions. The proportion of patients with relapses and the ARR in 1 year and in 2 years of therapy indicates that SamPEG-IFN-β1a is non-inferior to PEG-IFN-β1a in efficacy. SamPEG-IFN-B1a demonstrated a more favourable safety profile than PEG-IFN-B1a as showing less odds of SAEs and AEs leading to treatment discontinuation.
导言。β干扰素是治疗复发缓解型多发性硬化症(RRMS)的有效而安全的药物。为了提高患者的依从性,已开发出 PEG 化干扰素。目前尚未对 PEG 化干扰素的疗效和安全性进行直接比较。我们的目标是评估 SamPEG-IFN-β1a 与 PEG-IFN-β1a 在 RRMS 成年患者中的疗效和安全性。材料与方法。我们使用 PubMed、Embase 和 eLIBRARY.RU 数据库对随机临床试验 (RCT) 进行了系统检索。疗效根据治疗第一年和第二年复发患者的比例和年复发率(ARR)进行评估。安全性根据出现不良事件(AEs)、严重不良事件(SAEs)和任何导致治疗中止的不良事件的患者人数进行评估。我们进行了配对调整间接比较 (MAIC),以评估 PEG 化 IFNs 的疗效比较。为了评估疗效,我们检验了 SamPEG-IFN-β1a 对 PEG-IFN-β1a 的非劣效性假设和 SamPEG-IFN-β1a 对 PEG-IFN-β1a 的优效性假设。结果。根据系统综述的结果,选取了四篇文章,分别介绍了 PEG-IFN-β1a 3 期临床试验和 SamPEG-IFN-β1a 2-3 期临床试验的结果。PEG-IFN-β1a 组(n = 512)每两周给药一次,SamPEGIFN-β1a 组(n = 114)给药剂量为 240 μg。分析结果证实了 SamPEG-IFN-β1a 疗效不劣于 PEG-IFN-β1a 的假设,而 SamPEG-IFN-β1a 疗效优于 PEG-IFN-β1a 的假设未得到证实。在安全性方面,SamPEG-IFN-β1a优于PEG-IFN-β1a的假设也得到了证实,因为SAEs和导致治疗中断的AEs的发生率显著降低。结论治疗 1 年和 2 年的复发患者比例和 ARR 表明,SamPEG-IFN-β1a 的疗效不劣于 PEG-IFN-β1a。与 PEG-IFN-B1a 相比,SamPEG-IFN-B1a 的安全性更佳,因为出现 SAE 和导致治疗中断的 AE 的几率更低。
{"title":"Efficacy and Safety of PEGylated Interferons for Relapsing-Remitting Multiple Sclerosis in Adult Patients: Results of Matching-Adjusted Indirect Comparison","authors":"T. Simaniv, M. Zakharova, K. V. Sapozhnikov, D. Tolkacheva, Valeriia D. Sokolova, N. Sableva, O. Mironenko, Taras V. Khimich","doi":"10.54101/acen.2024.1.5","DOIUrl":"https://doi.org/10.54101/acen.2024.1.5","url":null,"abstract":"Introduction. Beta interferons are effective and safe agents for the treatment of relapsing-remitting multiple sclerosis (RRMS). PEGylated interferons have been developed in order to increase patient adherence. Direct comparisons of the efficacy and safety of PEGylated interferons have not yet been conducted. \u0000Our objective was to evaluate the efficacy and safety of SamPEG-IFN-β1a versus PEG-IFN-β1a in adult patients with RRMS. \u0000Materials and methods. We conducted a systematic search of randomized clinical trials (RCTs) using the PubMed, Embase and eLIBRARY.RU databases. Efficacy was assessed based on the proportion of patients with disease relapses and the annualized relapse rate (ARR) during the 1st and the 2nd years of treatment. Safety was assessed by the number of patients with adverse events (AEs), serious AEs (SAEs), and any AEs that led to the treatment discontinuation. We conducted pairwise matching-adjusted indirect comparison (MAIC) to assess comparative efficacy of PEGylated IFNs. To evaluate the efficacy, hypotheses of non-inferiority of SamPEG-IFN-β1a to PEG-IFN-β1a and superiority of SamPEG-IFN-β1a over PEG-IFN-β1a were tested. \u0000Results. Based on results of the systematic review, four articles were selected wherein the results of phase 3 clinical trial of PEG-IFN-β1a and phase 2–3 clinical trial of SamPEG-IFN-β1a were described. In PEG-IFN-β1a group (n = 512) the agent was administered once every 2 weeks, in SamPEGIFN-β1a group (n = 114) the agent was administered at a dose of 240 μg. The analysis results confirmed the hypothesis of SamPEG-IFN-β1a non-inferiority to PEG-IFN-β1a in efficacy, while SamPEG-IFN-β1a superiority over PEG-IFN-β1a in efficacy was not confirmed. The hypothesis of SamPEG-IFN-β1a superiority over PEG-IFN-β1a in safety was also confirmed based on a significantly lower incidence of SAEs and any AEs that led to treatment discontinuation. \u0000Conclusions. The proportion of patients with relapses and the ARR in 1 year and in 2 years of therapy indicates that SamPEG-IFN-β1a is non-inferior to PEG-IFN-β1a in efficacy. SamPEG-IFN-B1a demonstrated a more favourable safety profile than PEG-IFN-B1a as showing less odds of SAEs and AEs leading to treatment discontinuation.","PeriodicalId":36946,"journal":{"name":"Annals of Clinical and Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140740037","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
Neuroplasticity, music, and human brain 神经可塑性、音乐和人脑
Q3 Multidisciplinary Pub Date : 2024-04-05 DOI: 10.54101/acen.2024.1.8
I. Bogolepova, M. Krotenkova, R. N. Konovalov, P. A. Agapov, I. G. Malofeeva, A. T. Bikmeev
Introduction. Studying the influence of music on the human brain is one of the key topics in neuroscience as it allows extending our understanding of brain neuroplasticity. This study aimed to investigate structural brain organization in professional musicians. Materials and methods. We investigated 27 brains (i.e. 54 hemispheres) of male musicians, female musicians, male non-musicians, and female non-musicians by magnetic resonance imaging. All study participants were aged 20 to 30 years and did not have any mental or neurological disorders. Gray matter volume and cortex thickness in different cortical structures of the right and left hemispheres were measured. Results. We found major changes in the brain structure in professional musicians (both male and female) vs. non-musicians. We found differences in the macroscopic structure of the triangular region in the Broca’s motor speech area in musicians’ brain. Increases in gray matter volume in the brain of musicians and its individual cortical structures were shown in the superior temporal region, Broca’s motor speech area, hippocampus, superior parietal lobule, and other structures. We found increased thickness of cortical structures in musicians vs. non-musicians. Conclusions. Practicing music regularly was shown to change structural brain organization; we found significant increases in gray matter volume and cortex thickness in various cortical structures in the right and left brain hemispheres of musicians vs. non-musicians.
简介研究音乐对人脑的影响是神经科学的关键课题之一,因为它能扩展我们对脑神经可塑性的理解。本研究旨在调查专业音乐家的大脑结构组织。材料和方法我们通过磁共振成像对男性音乐家、女性音乐家、男性非音乐家和女性非音乐家的 27 个大脑(即 54 个半球)进行了研究。所有研究对象的年龄都在 20 至 30 岁之间,没有任何精神或神经方面的疾病。研究人员测量了左右半球不同皮质结构的灰质体积和皮质厚度。结果显示我们发现职业音乐家(包括男性和女性)与非音乐家相比,大脑结构发生了重大变化。我们发现音乐家大脑中布罗卡运动语言区三角形区域的宏观结构存在差异。在颞上区、布罗卡运动言语区、海马、顶叶上部和其他结构中,我们发现音乐家大脑灰质体积及其个别皮质结构有所增加。我们发现音乐家与非音乐家相比,大脑皮层结构的厚度有所增加。我们得出了结论。我们发现,与非音乐家相比,音乐家左右大脑半球的灰质体积和各种皮质结构的皮层厚度显著增加。
{"title":"Neuroplasticity, music, and human brain","authors":"I. Bogolepova, M. Krotenkova, R. N. Konovalov, P. A. Agapov, I. G. Malofeeva, A. T. Bikmeev","doi":"10.54101/acen.2024.1.8","DOIUrl":"https://doi.org/10.54101/acen.2024.1.8","url":null,"abstract":"Introduction. Studying the influence of music on the human brain is one of the key topics in neuroscience as it allows extending our understanding of brain neuroplasticity. \u0000This study aimed to investigate structural brain organization in professional musicians. \u0000Materials and methods. We investigated 27 brains (i.e. 54 hemispheres) of male musicians, female musicians, male non-musicians, and female non-musicians by magnetic resonance imaging. All study participants were aged 20 to 30 years and did not have any mental or neurological disorders. Gray matter volume and cortex thickness in different cortical structures of the right and left hemispheres were measured. \u0000Results. We found major changes in the brain structure in professional musicians (both male and female) vs. non-musicians. We found differences in the macroscopic structure of the triangular region in the Broca’s motor speech area in musicians’ brain. Increases in gray matter volume in the brain of musicians and its individual cortical structures were shown in the superior temporal region, Broca’s motor speech area, hippocampus, superior parietal lobule, and other structures. We found increased thickness of cortical structures in musicians vs. non-musicians. \u0000Conclusions. Practicing music regularly was shown to change structural brain organization; we found significant increases in gray matter volume and cortex thickness in various cortical structures in the right and left brain hemispheres of musicians vs. non-musicians.","PeriodicalId":36946,"journal":{"name":"Annals of Clinical and Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140736200","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
Neuroimaging Markers for Differential Diagnosis Between Multifocal Motor Neuropathy and Multifocal Acquired Demyelinating Sensory and Motor Neuropathy 用于鉴别诊断多灶性运动神经病和多灶性获得性脱髓鞘感觉和运动神经病的神经影像标志物
Q3 Multidisciplinary Pub Date : 2024-04-05 DOI: 10.54101/acen.2024.1.3
T. Tumilovich, V. V. Sinkova, D. Grishina, N. Suponeva, S. Morozova, M. Krotenkova, Anna V. Mansurova, A. Chechetkin
Introduction. Similar asymmetric patterns of motor disorders and neurophysiological changes complicate the differential diagnosis between multifocal motor neuropathy (MMN) and multifocal acquired demyelinating sensory and motor neuropathy (MADSAM) as two chronic dysimmune neuropathies with significantly different treatment approaches. The lack of specific paraclinical markers often result in misdiagnosis and selection of ineffective specific therapy. Identification of specific neuroimaging biomarkers to differentiate these conditions may improve diagnostic approaches. Objective: To identify neuroimaging markers for the differential diagnosis between MMN and MADSAM. Materials and methods. The study included 65 participants, particularly 30 individuals with MMN and 35 individuals with MADSAM followed up in the Center of Peripheral Nervous System Diseases, Research Center of Neurology, Moscow, Russia. We retrospectively analyzed their clinical and epidemiological characteristics as well as ultrasonography and magnetic resonance imaging (MRI) findings. Results. Ultrasonography was performed on the peripheral nerves of the upper extremities, the spinal nerves, and the brachial plexus. The results showed that participants with MADSAM had significantly greater cross-sectional areas (CSAs) and a higher incidence of intraneural ultrasonographic abnormalities compared to participants with MMN. CSA thresholds of the median nerves were identified using ROC analysis to differentiate between MMN and MADSAM. MRI scans of the brachial plexus revealed no abnormalities in 41.4% of the individuals with MMN and 27.3% of the individuals with MADSAM. Meanwhile, STIR hyperintense signal from the brachial plexus was most typical ( 70%) for the MADSAM group. Conclusions. This was the first detailed comparative analysis of neuroimaging findings in a large sample of patients with either MMN or MADSAM in Russia. Ultrasonographic markers for differential diagnosis have been determined. The advantages and limitations of ultrasonography and MRI of the brachial plexus and the spinal and peripheral nerves in diagnosing multifocal chronic dysimmune neuropathies have been demonstrated.
导言。多灶性运动神经病变(MMN)和多灶性获得性脱髓鞘感觉和运动神经病变(MADSAM)是两种慢性免疫功能紊乱性神经病,两者的运动障碍和神经生理学改变具有相似的非对称性,这使得两者之间的鉴别诊断变得更加复杂,两者的治疗方法也大相径庭。缺乏特异性临床旁标志物往往会导致误诊和选择无效的特异性疗法。鉴定特异性神经影像生物标志物以区分这些病症可改善诊断方法。目的确定用于鉴别诊断 MMN 和 MADSAM 的神经影像标志物。材料和方法。本研究包括 65 名参与者,其中 30 名 MMN 患者和 35 名 MADSAM 患者在俄罗斯莫斯科神经病学研究中心周围神经系统疾病中心接受随访。我们对他们的临床和流行病学特征以及超声波和磁共振成像(MRI)结果进行了回顾性分析。研究结果对上肢周围神经、脊神经和臂丛神经进行了超声波检查。结果显示,与 MMN 患者相比,MADSAM 患者的横截面积(CSA)明显更大,神经内超声异常的发生率更高。利用 ROC 分析确定了正中神经的 CSA 临界值,以区分 MMN 和 MADSAM。41.4% 的 MMN 患者和 27.3% 的 MADSAM 患者的臂丛核磁共振扫描未发现异常。同时,在MADSAM组中,来自臂丛的STIR高强度信号最为典型(70%)。结论。这是俄罗斯首次对大样本 MMN 或 MADSAM 患者的神经影像学结果进行详细比较分析。确定了用于鉴别诊断的超声标记。在诊断多灶性慢性免疫异常神经病时,臂丛神经和脊髓及周围神经的超声波和磁共振成像的优势和局限性已得到证实。
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引用次数: 0
Cell-Mediated Immunity in Multiple Sclerosis Patients Who Discontinued Therapy with an Integrin Inhibitor 停止整合素抑制剂治疗的多发性硬化症患者的细胞介导免疫功能
Q3 Multidisciplinary Pub Date : 2024-04-05 DOI: 10.54101/acen.2024.1.2
Yuliana A. Belova, Y. Chuksina, S. V. Kotov, I. A. Vasilenko
Introduction. Natalizumab (NTZ) is a humanized monoclonal antibody (mAb) that selectively inhibits α4-integrin adhesion molecule located on the surface of lymphocytes and prevents their trafficking into the central nervous system (CNS). The aim of this study was to identify characteristics of lymphocyte population and subpopulation pattern in the peripheral blood (PB) of multiple sclerosis (MS) patients who discontinued NTZ due to an increased risk of developing developing progressive multifocal leukoencephalopathy. Materials and methods. We conducted an open-label prospective observational study in 26 MS patients. Of those, 6 patients had rapidly progressive MS, 10 patients discontinued NTZ and had confirmed relapses afterwards, and 10 patients received NTZ and had no relapses during the washout period. Ten apparently healthy individuals were used as controls. Cell-mediated immunity parameters were evaluated by flow cytometry using a panel of mAbs to differentiation antigens of PB lymphocytes. Results. Patients who discontinued NTZ had significantly decreased absolute lymphocyte counts in PB, decreased T-cytotoxic, NKT and B1 lymphocyte subpopulation levels, and decreased activated T-cell (CD3+HLA–DR+) levels, which may be related to their redistribution, passing through the blood-brain barrier, and trafficking into the central nervous system. CD20+ В-cell levels did not differ from normal. Additional immune predictors of MS relapses after NTZ discontinuation can include decreased absolute count of PB lymphocytes and decreased percentage of CD3+CD8+ T-cell, NKT-cell, and B1-cell (CD19+CD5+) subpopulations. Significantly increased levels of CD25+- and CD38+-activated B-cells compared with the normal levels in naïve patients and subjects without relapses after NTZ discontinuation may suggest a high activation potential of the circulating B-cell pool and, therefore, a high risk of MS relapses. Conclusions. The changes in the lymphocyte subpopulation pattern in the PB of MS patients after NTZ discontinuation may have a prognostic value for assessing the risk of relapses; they justified switching patients to anti-B-cell therapy.
简介纳他珠单抗(NTZ)是一种人源化单克隆抗体(mAb),可选择性地抑制淋巴细胞表面的α4-整合素粘附分子,阻止淋巴细胞向中枢神经系统(CNS)迁移。本研究旨在确定多发性硬化症(MS)患者外周血(PB)中淋巴细胞群的特征和亚群模式,这些患者因患进行性多灶性白质脑病的风险增加而停用 NTZ。材料与方法。我们对 26 名多发性硬化症患者进行了开放标签前瞻性观察研究。其中,6 名患者为快速进展型多发性硬化症患者,10 名患者停用 NTZ 后确诊复发,10 名患者接受 NTZ 治疗后在冲洗期未复发。10 名表面健康的人作为对照组。采用流式细胞术评估了细胞介导的免疫参数,并使用了一组针对PB淋巴细胞分化抗原的mAbs。结果显示停用NTZ的患者PB中淋巴细胞绝对计数明显降低,T-细胞毒性、NKT和B1淋巴细胞亚群水平降低,活化T细胞(CD3+HLA-DR+)水平降低,这可能与它们重新分布、通过血脑屏障并进入中枢神经系统有关。CD20+ В-细胞水平与正常值无差异。NTZ停药后多发性硬化复发的其他免疫预测因素还包括PB淋巴细胞绝对数量的减少以及CD3+CD8+ T细胞、NKT细胞和B1细胞(CD19+CD5+)亚群百分比的降低。与正常水平相比,新患者和停用 NTZ 后未复发的受试者体内 CD25+- 和 CD38+- 活化 B 细胞的水平显著升高,这可能表明循环 B 细胞池具有很高的活化潜能,因此多发性硬化症复发的风险很高。结论停用NTZ后,多发性硬化症患者PB中淋巴细胞亚群模式的变化可能对评估复发风险具有预后价值;这些变化为患者转用抗B细胞疗法提供了依据。
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引用次数: 0
PreventS-MD®: a New Digital Technology to Maintain Cardiovascular Prevention in Routine Clinical Practice PreventS-MD®:在常规临床实践中保持心血管预防的新型数字技术
Q3 Multidisciplinary Pub Date : 2024-04-05 DOI: 10.54101/acen.2024.1.10
Mikhail A. Kravchenko, E. Gnedovskaya, Valery L. Feigin, M. Piradov
Stroke, myocardial infarction (MI), and other main non-communicable diseases (NCDs) remain major causes of mortality and disability globally. Up to 80% of cardiovascular events and up to 60% of NCDs are associated with potentially controlled risk factors (RFs). State-of-the-art digital technologies can help bridge the gap between evidence-based prevention methods and their critically low availability in routine clinical practice. An innovative digital platform named PreventS-MD® is a specially developed tool for healthcare professionals to be used under time constraints. With PreventS-MD®, clinicians can estimate patient's 10-year cardiovascular risk within several minutes. Then, they automatically get adapted results and recommendations to address identified RFs as well as graphical representation of specific RF contribution to overall stroke and MI risks. If some additional time is available, the clinician and the patient can collaboratively set customized achievable goals to correct modifiable RFs. An integrated analytical module provides healthcare managers with current digital risk profiles of the relevant population to evaluate prevention effectiveness and to forecast the load throughout the healthcare levels. PreventS-MD® has several unique advantages, including time-saving design, the function to activate motivated RF correction, individually tailored recommendations, and information on personally changed digital profiles of vascular risks. As cardiovascular diseases and main NCDs have a lot of common RFs, PreventS-MD® implemented into routine clinical practice will utilize a complex approach to the prevention of main NCDs, decreasing both stroke and MI burden and addressing complications of chronic pulmonary and kidney disease, tumors of any type, dementia, etc.
在全球范围内,中风、心肌梗塞(MI)和其他主要非传染性疾病(NCDs)仍然是导致死亡和残疾的主要原因。多达 80% 的心血管事件和多达 60% 的非传染性疾病与可能受控的风险因素 (RF) 有关。最先进的数字技术可以帮助弥合循证预防方法与这些方法在常规临床实践中极少使用之间的差距。名为 PreventS-MD® 的创新数字平台是专门为医疗保健专业人员开发的工具,可在时间有限的情况下使用。通过 PreventS-MD®,临床医生可以在几分钟内估算出患者 10 年的心血管风险。然后,他们会自动获得调整后的结果和建议,以解决已识别的射频问题,并以图表形式显示特定射频对总体中风和心肌梗死风险的影响。如果有额外的时间,临床医生和患者可以共同制定可实现的定制目标,以纠正可改变的射频。综合分析模块为医疗保健管理人员提供了相关人群的当前数字风险概况,以评估预防效果并预测整个医疗保健水平的负荷。PreventS-MD® 有几个独特的优势,包括省时设计、启动主动射频校正功能、量身定制的建议以及有关个人血管风险数字档案变化的信息。由于心血管疾病和主要非传染性疾病有许多共同的射频信号,因此将 PreventS-MD® 应用到常规临床实践中,将采用一种复杂的方法来预防主要非传染性疾病,减少中风和心肌梗死的负担,并解决慢性肺病和肾病、各种肿瘤、痴呆症等并发症。
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引用次数: 0
Key Risk Factors for Intracerebral Hemorrhage According to Regional Population-Based Stroke Registry 地区人群脑卒中登记显示的脑内出血主要风险因素
Q3 Multidisciplinary Pub Date : 2024-04-05 DOI: 10.54101/acen.2024.1.1
M. Yu. Maksimova, S. A. Chugunova
Introduction. Intracerebral hemorrhage (ICH) registry data allow assessing epidemiological parameters and risk factors in different age, gender, race, ethnicity, and other subgroups. This study aimed to evaluate the prevalence of key risk factors in a group of Yakutsk residents with primary hypertensive ICH included in the regional population-based stroke registry from 2015 to 2017. Materials and methods. This study of risk factors was conducted in patients with hypertensive ICH (n = 251) from the regional population-based stroke registry, including 133 (53%) men and 118 (47%) women of Asian or Caucasian races. We performed statistical analysis of data. Results. The analysis of risk factors showed that the prevalence of smoking and excessive alcohol consumption was higher in men with ICH compared with women (p 0.001). There were no statistically significant differences in the incidence of hypertension, history of myocardial infarction, dyslipidemia, or diabetes mellitus in patients with ICH in gender or ethnicity subgroups. Fibrillation and other heart diseases were more common in Caucasian patients than in Asian (p = 0.005). ICH was associated with high levels of low-density lipoproteins and triglycerides with low levels of total cholesterol and high-density lipoproteins compared with healthy individuals. Conclusions. We described gender and ethnic differences in the prevalence of risk factors in patients with hypertensive ICH.
导言。脑出血(ICH)登记数据可以评估不同年龄、性别、种族、民族和其他亚群的流行病学参数和风险因素。本研究旨在评估 2015 年至 2017 年期间纳入地区人群中风登记册的原发性高血压 ICH 雅库茨克居民群体中主要风险因素的患病率。材料与方法。这项风险因素研究的对象是来自地区人口中风登记处的高血压 ICH 患者(n = 251),其中包括 133 名(53%)男性和 118 名(47%)亚裔或高加索裔女性。我们对数据进行了统计分析。结果显示风险因素分析表明,与女性相比,男性 ICH 患者吸烟和过度饮酒的比例更高(P 0.001)。ICH患者中高血压、心肌梗死病史、血脂异常或糖尿病的发病率在性别或种族亚组中没有明显的统计学差异。白种人比亚洲人更容易患心颤和其他心脏病(P = 0.005)。与健康人相比,ICH 患者的低密度脂蛋白和甘油三酯水平较高,而总胆固醇和高密度脂蛋白水平较低。结论。我们描述了高血压 ICH 患者危险因素发生率的性别和种族差异。
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引用次数: 0
3,5-Dimethyladamantan-1-amine Restores Short-term Synaptic Plasticity by Changing Function of Excitatory Amino Acid Transporters in Mouse Model of Spinocerebellar Ataxia Type 1 3,5-二甲基金刚烷-1-胺通过改变兴奋性氨基酸转运体的功能恢复脊髓小脑共济失调 1 型小鼠模型的短期突触可塑性
Q3 Multidisciplinary Pub Date : 2024-04-05 DOI: 10.54101/acen.2024.1.7
O. Belozor, A. A. Vasilev, Alexandra G. Mileiko, Liudmila D. Mosina, Ilya G. Mikhailov, A. Shuvaev, A. Shuvaev
Introduction. Memantine is an agent that used for treatment of Alzheimer's type dementia. Memantine considerably reduces the effects of neurodegeneration, may potentially slow down the neurodegenerative changes in the cerebellum and may act as treatment of choice for spinocerebellar ataxia type 1 (SCA 1). Our objective was to study molecular mechanisms of the short-term synaptic plasticity improvement associated with long-term memantine use in SCA 1 transgenic mice. Materials and methods. The experiments were performed on 12-week-old CD1 mice. We created a mouse model of cerebellar astrogliosis after expression of mutant ataxin-1 (ATXN1[Q85]) in the Bergmann glia (BG). To model the astrocyte-mediated neurodegeneration in the cerebellum, the mice were injected with LVV GFAP-Flag-ATXN1[Q85] lentiviral vector (LVV) constructs intracortically. Some of the mice received 0.35 mg/kg memantine dissolved in drink water once daily for 9 weeks. The control animals were administered LVV GFAP-ATXN1[Q2]-Flag. Changes of the excitatory postsynaptic currents amplitudes from Purkinje cells (PC) were recorded by patch clamp. Expression of anti-EAAT1 in the cerebellar cortex was assessed using immunohistochemistry. Results. The reactive glia of the cerebellar cortex in SCA1 mice is characterized by a decrease in the immunoreactivity of anti-EAAT1, while chronic memantine use restores this capacity. The decay time of the excitatory postsynaptic current amplitude in the parallel fiber-Purkinje cell (PF-PC) synapses of the SCA1 mice is considerably longer, which indicates the slowing of glutamate reuptake and EAAT1 dysfunction. The prolonged presence of increased neurotransmitter levels in the synaptic cleft facilitates activation of the mGluR1 signaling and restoration of mGluR1-dependent synaptic plasticity in Purkinje cells of the SCA1 mice. Conclusions. The slowing of neurotransmitter reuptake associated with long-term memantine treatment improves mGluR1-dependent short-term synaptic plasticity of the Purkinje cells in the SCA1 mice. Restoration of synaptic plasticity in these animals may underlie partial reduction of ataxic syndrome.
简介美金刚是一种用于治疗阿尔茨海默型痴呆症的药物。美金刚能显著减轻神经退行性变的影响,有可能减缓小脑神经退行性变,并可作为治疗脊髓小脑共济失调 1 型(SCA 1)的首选药物。我们的目的是研究在 SCA 1 转基因小鼠中长期使用美金刚的短期突触可塑性改善的分子机制。材料和方法。实验在 12 周大的 CD1 小鼠身上进行。我们在伯格曼胶质细胞(BG)中表达突变型共济失调素-1(ATXN1[Q85])后建立了小脑星形胶质细胞病变的小鼠模型。为了模拟小脑星形胶质细胞介导的神经变性,小鼠皮质内注射了 LVV GFAP-Flag-ATXN1[Q85] 慢病毒载体(LVV)构建体。其中一些小鼠接受了溶于饮用水中的 0.35 mg/kg 美金刚,每天一次,持续 9 周。对照组动物则接受 LVV GFAP-ATXN1[Q2]-Flag 的治疗。通过膜片钳记录来自浦肯野细胞(PC)的兴奋性突触后电流振幅的变化。用免疫组化方法评估小脑皮质中抗EAAT1的表达。结果显示SCA1小鼠小脑皮质反应性神经胶质的特点是抗EAAT1的免疫活性降低,而长期服用美金刚则可恢复这种能力。SCA1 小鼠平行纤维-浦肯野细胞(PF-PC)突触中兴奋性突触后电流幅度的衰减时间大大延长,这表明谷氨酸再摄取减慢和 EAAT1 功能障碍。突触间隙中神经递质水平的长期增高促进了 mGluR1 信号的激活,并恢复了 SCA1 小鼠浦肯野细胞中依赖于 mGluR1 的突触可塑性。结论长期美金刚治疗可减缓神经递质的再摄取,从而改善 SCA1 小鼠普肯列细胞的 mGluR1 依赖性短期突触可塑性。这些动物突触可塑性的恢复可能是共济失调综合征部分减轻的原因。
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引用次数: 0
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Annals of Clinical and Experimental Neurology
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