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Independent risk factors for in-hospital outcome of myasthenic crisis: a prospective cohort study. 肌无力危象院内预后的独立风险因素:一项前瞻性队列研究。
IF 5.9 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-02-09 eCollection Date: 2024-01-01 DOI: 10.1177/17562864241226745
Yuan Wang, Xiao Huan, Xinfang Zhu, Jie Song, Chong Yan, Lei Yang, Caihua Xi, Yafang Xu, Jianying Xi, Chongbo Zhao, Rong Xia, Sushan Luo

Background: Myasthenic crisis (MC) is a life-threatening condition for myasthenia gravis (MG). Therapeutic plasma exchange (TPE) and intravenous immunoglobulin (IVIg) efficaciously treat patients with MC. However, not every MC responds well to rescue therapies, and the determinants for outcome with the evidence from prospective cohorts are still lacking.

Objectives: To explore the risk factors for in-hospital outcomes in patients with MC.

Methods: Using a national neuromuscular center-based cohort of MG with prospective follow-ups from the crisis to the post-crisis phase, we finally included 90 MC episodes from 76 independent patients who received a standard regimen of rescue therapies.

Results: The mean admission age was 52.89 ± 15.72 years. With a female predominance of 63.16% (48/76) and a high proportion of thymoma-associated MG (TMG) of 63.16% (48/76), the overall in-hospital mortality was 2.63% (2/76) and the average duration for mechanical ventilation (MV) use was 17.09 ± 13.36 days (0-53 days). In contrast to the patients with anti-acetylcholine receptor (AChR) antibodies, muscle-specific tyrosine kinase (MuSK)-associated MC exhibited a shorter MV support (5.20 ± 5.07 versus 17.40 ± 13.24 days, p = 0.023), length of intensive care units (ICU) stay (6.00 ± 4.64 versus 19.16 ± 17.54 days, p = 0.046), and hospital stay (16.00 ± 4.12 versus 34.43 ± 20.48 days, p = 0.011). Thymoma [odds ratio (OR): 0.200, 95% confidence interval (CI): 0.058-0.687, p = 0.011], partial pressure of carbon dioxide (PCO2) in blood gas before MV (OR: 1.238, 95% CI: 1.015-1.510, p = 0.035), and pneumonia (OR: 0.204, 95% CI: 0.049-0.841, p = 0.028) were identified as independent risk factors for prolonged MV use. TMG patients with thymoma burden exhibited a notable longer MV use (22.08 ± 17.54 versus 8.88 ± 6.79 days, p = 0.001), a prolonged hospital stay (40.40 ± 26.13 versus 23.67 ± 13.83 days, p = 0.009) compared with non-TMG. Even with complete thymoma resection (R0), TMG exhibited an unfavorable outcome versus non-TMG.

Conclusion: With timely rescue therapies and prospective follow-ups, the in-hospital outcome of MCs was substantially improved. Thymoma, PCO2 in blood gas before MV, and pneumonia were identified as independent risk factors for prolonged MV use.

背景:肌无力危象(MC)是一种危及重症肌无力(MG)患者生命的疾病。治疗性血浆置换(TPE)和静脉注射免疫球蛋白(IVIg)可有效治疗 MC 患者。然而,并不是每一位重症肌无力患者都能对抢救疗法做出良好反应,而且目前仍缺乏前瞻性队列研究的证据来确定治疗结果的决定因素:目的:探讨MC患者院内预后的风险因素:我们使用了一个基于全国神经肌肉中心的 MG 队列,从危机到危机后阶段进行了前瞻性随访,最终纳入了 76 名独立患者的 90 次 MC 事件,这些患者接受了标准的抢救治疗方案:平均入院年龄为(52.89 ± 15.72)岁。女性占 63.16%(48/76),胸腺瘤相关 MG(TMG)占 63.16%(48/76),院内总死亡率为 2.63%(2/76),使用机械通气(MV)的平均时间为 17.09 ± 13.36 天(0-53 天)。与抗乙酰胆碱受体(AChR)抗体患者相比,肌肉特异性酪氨酸激酶(MuSK)相关 MC 的机械通气支持时间更短(5.20 ± 5.07 对 17.40 ± 13.36 天,P = 0.0.0)。24 天,p = 0.023)、重症监护室(ICU)住院时间(6.00 ± 4.64 对 19.16 ± 17.54 天,p = 0.046)和住院时间(16.00 ± 4.12 对 34.43 ± 20.48 天,p = 0.011)。胸腺瘤[几率比(OR):0.200,95% 置信区间(CI):0.058-0.687,p = 0.011]、MV 前血气中二氧化碳分压(PCO2)(OR:1.238,95% CI:1.015-1.510,p = 0.035)和肺炎(OR:0.204,95% CI:0.049-0.841,p = 0.028)被确定为延长 MV 使用时间的独立风险因素。与非胸腺瘤患者相比,有胸腺瘤负担的 TMG 患者使用 MV 的时间明显更长(22.08 ± 17.54 对 8.88 ± 6.79 天,p = 0.001),住院时间也更长(40.40 ± 26.13 对 23.67 ± 13.83 天,p = 0.009)。即使胸腺瘤完全切除(R0),TMG与非TMG相比也显示出不利的预后:结论:通过及时的抢救治疗和前瞻性随访,MC 的院内预后得到了显著改善。胸腺瘤、中风前血气中的 PCO2 和肺炎被确定为中风使用时间延长的独立风险因素。
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引用次数: 0
Prognostic relevance of MRI in early relapsing multiple sclerosis: ready to guide treatment decision making? 磁共振成像对早期复发性多发性硬化症的预后相关性:能否为治疗决策提供指导?
IF 5.9 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-02-07 eCollection Date: 2024-01-01 DOI: 10.1177/17562864241229325
Olaf Hoffmann, Ralf Gold, Sven G Meuth, Ralf A Linker, Thomas Skripuletz, Heinz Wiendl, Mike P Wattjes

Magnetic resonance imaging (MRI) of the brain and spinal cord plays a crucial role in the diagnosis and monitoring of multiple sclerosis (MS). There is conclusive evidence that brain and spinal cord MRI findings in early disease stages also provide relevant insight into individual prognosis. This includes prediction of disease activity and disease progression, the accumulation of long-term disability and the conversion to secondary progressive MS. The extent to which these MRI findings should influence treatment decisions remains a subject of ongoing discussion. The aim of this review is to present and discuss the current knowledge and scientific evidence regarding the utility of MRI at early MS disease stages for prognostic classification of individual patients. In addition, we discuss the current evidence regarding the use of MRI in order to predict treatment response. Finally, we propose a potential approach as to how MRI data may be categorized and integrated into early clinical decision making.

大脑和脊髓的磁共振成像(MRI)在多发性硬化症(MS)的诊断和监测中起着至关重要的作用。有确凿证据表明,疾病早期阶段的脑和脊髓磁共振成像检查结果也能为个体预后提供相关信息。这包括预测疾病活动和疾病进展、长期残疾的累积以及向继发性进展多发性硬化症的转化。这些 MRI 检查结果应在多大程度上影响治疗决策仍是一个持续讨论的话题。本综述旨在介绍和讨论有关磁共振成像在早期多发性硬化症疾病阶段用于个体患者预后分类的实用性的现有知识和科学证据。此外,我们还讨论了有关使用 MRI 预测治疗反应的现有证据。最后,我们就如何对 MRI 数据进行分类并将其整合到早期临床决策中提出了一种可能的方法。
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引用次数: 0
Promising advances in Alzheimer's treatment: donanemab's impact on disease progression and amyloid clearance. 阿尔茨海默氏症治疗有望取得进展:多那尼单抗对疾病进展和淀粉样蛋白清除的影响。
IF 4.7 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-01-30 eCollection Date: 2024-01-01 DOI: 10.1177/17562864241228650
Abdul Wahid, Wajiha Fatima Khan, Yusra Khan
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引用次数: 0
Intrinsic brain activity differences in perampanel-responsive and non-responsive drug-resistant epilepsy patients: an EEG microstate analysis. 对 perampanel 有反应和无反应的耐药性癫痫患者大脑活动的内在差异:脑电图微状态分析。
IF 4.7 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-01-30 eCollection Date: 2024-01-01 DOI: 10.1177/17562864241227293
Chaofeng Zhu, Juan Li, Dazhu Wei, Luyan Wu, Yuying Zhang, Huapin Huang, Wanhui Lin

Background: Drug-resistant epilepsy (DRE) patients exhibit aberrant large-scale brain networks. Perampanel may be a therapeutic option for controlling seizures in these patients.

Objective: We aim to explore the differences of resting-state electroencephalogram (EEG) microstate in perampanel-responsive and non-responsive DRE patients.

Design: Retrospective study.

Methods: Clinical data were collected from DRE patients who received perampanel treatment at the Fujian Medical University Union Hospital from June 2020 to September 2021, with a minimum follow-up of 6 months. Patients were classified into three groups based on the extent of reduction in seizure frequency: non-responsive (seizure reduction <50%), responsive (seizure reduction >50% but not seizure-free), and seizure-free. Resting-state EEG data sets of all participants were subjected to EEG microstate analysis. The study comprehensively compared the mean duration, frequency per second, and temporal coverage of each microstate among the three groups.

Results: A total of 76 perampanel-treated DRE patients were categorized into three groups based on their response to treatment: non-responsive (n = 20), responsive (n = 36), and seizure-free (n = 20), according to the degree of seizure frequency reduction. The results of EEG microstate analysis revealed no statistically significant distinctions in frequency, duration, and coverage of microstate D in these DRE patients. However, the seizure-free group showed significantly increased duration and coverage of microstate A, frequency and coverage of microstate B, and significantly decreased duration, frequency, and coverage of microstate C when compared with the other groups.

Conclusion: Microstate A, B, and D is associated with the sensorimotor network, visual network, salience network, and attention network, respectively. This study demonstrates statistically significant differences in the sensorimotor, visual, and salience networks, but not in the attention network, between perampanel-responsive and non-responsive DRE patients.

背景:耐药性癫痫(DRE)患者表现出异常的大规模大脑网络。佩兰帕奈可能是控制这些患者癫痫发作的一种治疗选择:目的:我们旨在探索对培南帕尼有反应和无反应的 DRE 患者静息态脑电图(EEG)微状态的差异:设计:回顾性研究:收集2020年6月至2021年9月在福建医科大学附属协和医院接受培南治疗的DRE患者的临床资料,随访至少6个月。根据癫痫发作频率的减少程度将患者分为三组:无应答组(癫痫发作减少 50%,但未达到无发作)和无发作组。对所有参与者的静息态脑电图数据集进行了脑电图微状态分析。研究全面比较了三个组别中每个微状态的平均持续时间、每秒频率和时间覆盖范围:根据患者对治疗的反应,共将76名接受过perampanel治疗的DRE患者分为三组:无反应组(20人)、有反应组(36人)和无发作组(20人)。脑电图微状态分析结果显示,这些 DRE 患者在微状态 D 的频率、持续时间和覆盖范围方面没有明显的统计学差异。然而,与其他组相比,无癫痫发作组的微状态 A 的持续时间和覆盖范围、微状态 B 的频率和覆盖范围明显增加,而微状态 C 的持续时间、频率和覆盖范围则明显减少:结论:微状态 A、B 和 D 分别与感觉运动网络、视觉网络、显著性网络和注意力网络有关。本研究表明,对培南有反应和对培南无反应的眩晕症患者在感觉运动网络、视觉网络和显著性网络方面存在统计学意义上的显著差异,但在注意力网络方面没有差异。
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引用次数: 0
Efficacy of bortezomib, cyclophosphamide, and dexamethasone for newly diagnosed POEMS syndrome patients. 硼替佐米、环磷酰胺和地塞米松对新诊断的 POEMS 综合征患者的疗效。
IF 4.7 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-01-27 eCollection Date: 2024-01-01 DOI: 10.1177/17562864231219151
Fang Fang, Xiao-Xi Lan, Rong-Hua Hu, Wu-Han Hui, Hong Zhao, Yi-Xian Guo, Bing-Xin Ji, Hong-Jun Liu, Li Su, Wan-Ling Sun

Background: Due to the rarity of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, the best first-line treatment has not been established, although there are several options in guidelines. The preferred treatments vary according to the preference of the physician and anecdote.

Objectives: First, to analyze the efficacy of a new treatment mode in POEMS syndrome that uses the four-cycle treatment as the induction regimen, followed by sequential transplantation as the consolidation regimen for transplantation-eligible patients, or received another two-cycle treatment for transplantation-ineligible patients. Second, to compare the efficacy and safety of regimens with a proteasome inhibitor (bortezomib-cyclophosphamide-dexamethasone, BCD) or without a proteasome inhibitor (cyclophosphamide-dexamethasone ± thalidomide, CD ± T).

Design: We conducted a retrospective study using real-world data from Capital Medical University, Xuanwu Hospital.

Methods: A total of 34 newly diagnosed POEMS syndrome patients met Dispenzieri's diagnostic criteria, and those who completed at least four cycles of treatment from July 2013 to March 2021 were included.

Results: The overall vascular endothelial growth factor (VEGF) response rate of this new treatment mode was 100%. The cumulative VEGF complete remission (CRV) rate was 67.9%, and the cumulative complete hematological response (CRH) rate was 55.6%. During the median 49-month follow-up, the 5-year-overall survival (OS) rate was 90.7%, the 3-year-progression-free survival (PFS) rate was 78.4%, and the 5-year-PFS rate was 73.8%. The BCD regimen achieved a 75% CRV rate (median time from diagnosis to CRV = 130 days) and 66.7% CRH rate (median time from diagnosis to CRH = 218 days). In addition, the VEGF response was less than the partial remission (PRV) after four-cycle induction treatment, which, together with a decrease on the Overall Neurological Limitation Scale of less than three points 1 year after consolidation treatment, was an independent poor prognostic factor.

Conclusion: Bortezomib was well-tolerated by patients with POEMS syndrome. Compared with CD ± T regimen, BCD as the induction regimen achieved better VEGF response and earlier hematological remission. Autologous stem cell transplantation used as consolidation therapy further improved the neurological and hematological remission rates, resulting in better OS and PFS.

背景:由于多发性神经病、器官肥大、内分泌病、单克隆丙种球蛋白病和皮肤改变(POEMS)综合征的罕见性,尽管指南中有多种选择,但最佳的一线治疗方法尚未确定。首选治疗方法因医生的偏好和轶事而异:首先,分析一种新的 POEMS 综合征治疗模式的疗效,该模式以四周期治疗作为诱导治疗方案,然后对符合移植条件的患者以序贯移植作为巩固治疗方案,或对不符合移植条件的患者接受另一种两周期治疗。其次,比较使用蛋白酶体抑制剂(硼替佐米-环磷酰胺-地塞米松,BCD)或不使用蛋白酶体抑制剂(环磷酰胺-地塞米松±沙利度胺,CD±T)的治疗方案的疗效和安全性:我们利用首都医科大学宣武医院的真实数据进行了一项回顾性研究:方法:共纳入34例符合Dispenzieri诊断标准的新诊断POEMS综合征患者,这些患者在2013年7月至2021年3月期间完成了至少4个周期的治疗:这种新治疗模式的血管内皮生长因子(VEGF)总反应率为100%。累积血管内皮生长因子完全缓解(CRV)率为67.9%,累积完全血液学反应(CRH)率为55.6%。在中位 49 个月的随访中,5 年总生存期(OS)为 90.7%,3 年无进展生存期(PFS)为 78.4%,5 年无进展生存期(PFS)为 73.8%。BCD方案的CRV率为75%(从诊断到CRV的中位时间=130天),CRH率为66.7%(从诊断到CRH的中位时间=218天)。此外,四周期诱导治疗后,VEGF反应低于部分缓解(PRV),再加上巩固治疗1年后神经功能总限制量表下降少于3分,这是一个独立的不良预后因素:结论:POEMS综合征患者对硼替佐米耐受性良好。结论:硼替佐米对POEMS综合征患者的耐受性良好,与CD±T方案相比,BCD作为诱导方案可获得更好的血管内皮生长因子反应和更早的血液学缓解。自体干细胞移植作为巩固治疗进一步提高了神经和血液学缓解率,从而改善了OS和PFS。
{"title":"Efficacy of bortezomib, cyclophosphamide, and dexamethasone for newly diagnosed POEMS syndrome patients.","authors":"Fang Fang, Xiao-Xi Lan, Rong-Hua Hu, Wu-Han Hui, Hong Zhao, Yi-Xian Guo, Bing-Xin Ji, Hong-Jun Liu, Li Su, Wan-Ling Sun","doi":"10.1177/17562864231219151","DOIUrl":"10.1177/17562864231219151","url":null,"abstract":"<p><strong>Background: </strong>Due to the rarity of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, the best first-line treatment has not been established, although there are several options in guidelines. The preferred treatments vary according to the preference of the physician and anecdote.</p><p><strong>Objectives: </strong>First, to analyze the efficacy of a new treatment mode in POEMS syndrome that uses the four-cycle treatment as the induction regimen, followed by sequential transplantation as the consolidation regimen for transplantation-eligible patients, or received another two-cycle treatment for transplantation-ineligible patients. Second, to compare the efficacy and safety of regimens with a proteasome inhibitor (bortezomib-cyclophosphamide-dexamethasone, BCD) or without a proteasome inhibitor (cyclophosphamide-dexamethasone ± thalidomide, CD ± T).</p><p><strong>Design: </strong>We conducted a retrospective study using real-world data from Capital Medical University, Xuanwu Hospital.</p><p><strong>Methods: </strong>A total of 34 newly diagnosed POEMS syndrome patients met Dispenzieri's diagnostic criteria, and those who completed at least four cycles of treatment from July 2013 to March 2021 were included.</p><p><strong>Results: </strong>The overall vascular endothelial growth factor (VEGF) response rate of this new treatment mode was 100%. The cumulative VEGF complete remission (CR<sub>V</sub>) rate was 67.9%, and the cumulative complete hematological response (CR<sub>H</sub>) rate was 55.6%. During the median 49-month follow-up, the 5-year-overall survival (OS) rate was 90.7%, the 3-year-progression-free survival (PFS) rate was 78.4%, and the 5-year-PFS rate was 73.8%. The BCD regimen achieved a 75% CR<sub>V</sub> rate (median time from diagnosis to CR<sub>V</sub> = 130 days) and 66.7% CR<sub>H</sub> rate (median time from diagnosis to CR<sub>H</sub> = 218 days). In addition, the VEGF response was less than the partial remission (PR<sub>V</sub>) after four-cycle induction treatment, which, together with a decrease on the Overall Neurological Limitation Scale of less than three points 1 year after consolidation treatment, was an independent poor prognostic factor.</p><p><strong>Conclusion: </strong>Bortezomib was well-tolerated by patients with POEMS syndrome. Compared with CD ± T regimen, BCD as the induction regimen achieved better VEGF response and earlier hematological remission. Autologous stem cell transplantation used as consolidation therapy further improved the neurological and hematological remission rates, resulting in better OS and PFS.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864231219151"},"PeriodicalIF":4.7,"publicationDate":"2024-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10823847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139576258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effect of altered gene expression in lipid metabolism on cognitive improvement in patients with Alzheimer's dementia following fecal microbiota transplantation: a preliminary study. 粪便微生物群移植后脂质代谢基因表达的改变对阿尔茨海默氏症痴呆患者认知能力改善的影响:一项初步研究。
IF 5.9 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-01-19 eCollection Date: 2024-01-01 DOI: 10.1177/17562864231218181
Jun-Seob Kim, Hyelim Park, Jung-Hwan Lee, Jongbeom Shin, Boram Cha, Kye Sook Kwon, Yong Woon Shin, Yerim Kim, YeoJin Kim, Jong Seok Bae, Ju-Hun Lee, Seok-Jin Choi, Tae Jung Kim, Sang-Bae Ko, Soo-Hyun Park

Background: The brain-gut axis has emerged as a potential target in neurodegenerative diseases, including dementia, as individuals with dementia exhibit distinct gut microbiota compositions. Fecal microbiota transplantation (FMT), the transfer of fecal solution from a healthy donor to a patient, has shown promise in restoring homeostasis and cognitive enhancement.

Objective: This study aimed to explore the effects of FMT on specific cognitive performance measures in Alzheimer's dementia (AD) patients and investigate the relationship between cognition and the gut microbiota by evaluating changes in gene expression following FMT.

Methods: Five AD patients underwent FMT, and their cognitive function [Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB)] was assessed before and after FMT. The patients' fecal samples were analyzed with 16S rRNA to compare the composition of their gut microbiota. We also assessed modifications in the serum mRNA expression of patients' genes related to lipid metabolism using serum RNA sequencing and quantitative real-time polymerase chain reaction.

Results: Significant improvements in cognitive function, as measured by the MMSE (pre- and post-FMT was 13.00 and 18.00) and MoCA were seen. The MoCA scores at 3 months post-FMT (21.0) were the highest (12.0). The CDR-SOB scores at pre- and post-FMT were 10.00 and 5.50, respectively. Analysis of the gut microbiome composition revealed changes via 16S rRNA sequencing with an increase in Bacteroidaceae and a decrease in Enterococcaceae. Gene expression analysis identified alterations in lipid metabolism-related genes after FMT.

Conclusion: These findings suggest a link between alterations in the gut microbiome, gene expression related to lipid metabolism, and cognitive function. The study highlights the importance of gut microbiota in cognitive function and provides insights into potential biomarkers for cognitive decline progression. FMT could complement existing therapies and show potential as a therapeutic intervention to mitigate cognitive decline in AD.

背景:大脑-肠道轴已成为包括痴呆症在内的神经退行性疾病的潜在靶点,因为痴呆症患者表现出不同的肠道微生物群组成。粪便微生物群移植(FMT),即把健康捐赠者的粪便溶液转移到患者体内,已显示出恢复平衡和提高认知能力的前景:本研究旨在探讨肠道微生物群移植对阿尔茨海默氏症痴呆症(AD)患者特定认知表现指标的影响,并通过评估肠道微生物群移植后基因表达的变化,研究认知与肠道微生物群之间的关系:五名阿尔茨海默氏痴呆症(AD)患者接受了肠道微生物治疗,并在肠道微生物治疗前后评估了他们的认知功能[迷你精神状态检查(MMSE)、蒙特利尔认知评估(MoCA)和临床痴呆评定量表方格总和(CDR-SOB)]。用 16S rRNA 分析了患者的粪便样本,以比较其肠道微生物群的组成。我们还使用血清 RNA 测序和定量实时聚合酶链反应评估了患者血清中与脂质代谢相关基因的 mRNA 表达变化:通过MMSE(FMT前后分别为13.00和18.00)和MoCA测量,患者的认知功能有明显改善。FMT 术后 3 个月的 MoCA 评分(21.0)最高(12.0)。FMT前后的CDR-SOB得分分别为10.00和5.50。通过 16S rRNA 测序分析,肠道微生物组的组成发生了变化,类杆菌科(Bacteroidaceae)的微生物增加,肠球菌科(Enterococcaceae)的微生物减少。基因表达分析发现,FMT后脂质代谢相关基因发生了改变:这些研究结果表明,肠道微生物组的改变、脂质代谢相关基因的表达与认知功能之间存在联系。该研究强调了肠道微生物群在认知功能中的重要性,并为认知功能衰退进展的潜在生物标志物提供了见解。FMT可以补充现有疗法的不足,并显示出作为一种治疗干预措施缓解AD认知功能衰退的潜力。
{"title":"Effect of altered gene expression in lipid metabolism on cognitive improvement in patients with Alzheimer's dementia following fecal microbiota transplantation: a preliminary study.","authors":"Jun-Seob Kim, Hyelim Park, Jung-Hwan Lee, Jongbeom Shin, Boram Cha, Kye Sook Kwon, Yong Woon Shin, Yerim Kim, YeoJin Kim, Jong Seok Bae, Ju-Hun Lee, Seok-Jin Choi, Tae Jung Kim, Sang-Bae Ko, Soo-Hyun Park","doi":"10.1177/17562864231218181","DOIUrl":"10.1177/17562864231218181","url":null,"abstract":"<p><strong>Background: </strong>The brain-gut axis has emerged as a potential target in neurodegenerative diseases, including dementia, as individuals with dementia exhibit distinct gut microbiota compositions. Fecal microbiota transplantation (FMT), the transfer of fecal solution from a healthy donor to a patient, has shown promise in restoring homeostasis and cognitive enhancement.</p><p><strong>Objective: </strong>This study aimed to explore the effects of FMT on specific cognitive performance measures in Alzheimer's dementia (AD) patients and investigate the relationship between cognition and the gut microbiota by evaluating changes in gene expression following FMT.</p><p><strong>Methods: </strong>Five AD patients underwent FMT, and their cognitive function [Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB)] was assessed before and after FMT. The patients' fecal samples were analyzed with 16S rRNA to compare the composition of their gut microbiota. We also assessed modifications in the serum mRNA expression of patients' genes related to lipid metabolism using serum RNA sequencing and quantitative real-time polymerase chain reaction.</p><p><strong>Results: </strong>Significant improvements in cognitive function, as measured by the MMSE (pre- and post-FMT was 13.00 and 18.00) and MoCA were seen. The MoCA scores at 3 months post-FMT (21.0) were the highest (12.0). The CDR-SOB scores at pre- and post-FMT were 10.00 and 5.50, respectively. Analysis of the gut microbiome composition revealed changes <i>via</i> 16S rRNA sequencing with an increase in Bacteroidaceae and a decrease in Enterococcaceae. Gene expression analysis identified alterations in lipid metabolism-related genes after FMT.</p><p><strong>Conclusion: </strong>These findings suggest a link between alterations in the gut microbiome, gene expression related to lipid metabolism, and cognitive function. The study highlights the importance of gut microbiota in cognitive function and provides insights into potential biomarkers for cognitive decline progression. FMT could complement existing therapies and show potential as a therapeutic intervention to mitigate cognitive decline in AD.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"17 ","pages":"17562864231218181"},"PeriodicalIF":5.9,"publicationDate":"2024-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10799597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139511726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genetic and phenotypic analyses of PRRT2 positive and negative paroxysmal kinesigenic dyskinesia. PRRT2 阳性和阴性阵发性运动障碍的遗传和表型分析。
IF 5.9 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-01-18 eCollection Date: 2024-01-01 DOI: 10.1177/17562864231224110
Yingying Zhang, Jiechuan Ren, Tianhua Yang, Weixi Xiong, Linyuan Qin, Dongmei An, Fayun Hu, Dong Zhou

Background: Paroxysmal kinesigenic dyskinesia (PKD) is a rare neurological disorder, characterized by attacks of involuntary movements triggered by sudden action. Variants in proline-rich transmembrane protein 2 (PRRT2) are the most common genetic cause of PKD.

Objective: The objective was to investigate the clinical and genetic characteristics of PKD and to establish genotype-phenotype correlations.

Methods: We enrolled 219 PKD patients, documented their clinical information and performed PRRT2 screening using Sanger sequencing. Whole exome sequencing was performed on 49 PKD probands without PRRT2 variants. Genotype-phenotype correlation analyses were conducted on the probands.

Results: Among 219 PKD patients (99 cases from 39 families and 120 sporadic cases), 16 PRRT2 variants were identified. Nine variants (c.879+4A>G, c.879+5G>A, c.856G>A, c.955G>T, c.884G>C, c.649C>T, c.649dupC, c.649delC and c.696_697delCA) were previously known, while seven were novel (c.367_403del, c.347_348delAA, c.835C>T, c.116dupC, c.837_838insC, c.916_937del and c.902G>A). The mean interval from onset to diagnosis was 7.94 years. Compared to patients without PRRT2 variants, patients with the variants were more likely to have a positive family history, an earlier age of onset and a higher prevalence of falls during pre-treatment attacks (27.14% versus 8.99%, respectively). Patients with truncated PRRT2 variants tend to have bilateral attacks. We identified two transmembrane protein 151A (TMEM151A) variants including a novel variant (c.368G>C) and a reported variant (c.203C>T) in two PRRT2-negative probands with PKD.

Conclusion: These findings provide insights on the clinical characteristics, diagnostic timeline and treatment response of PKD patients. PKD patients with truncated PRRT2 variants may tend to have more severe paroxysmal symptoms. This study expands the spectrum of PRRT2 and TMEM151A variants. Carbamazepine and oxcarbazepine are both used as a first-line treatment choice for PKD patients.

背景:阵发性运动障碍(PKD)是一种罕见的神经系统疾病,其特征是由突然动作引发的不自主运动。富脯氨酸跨膜蛋白 2(PRRT2)的变异是 PKD 最常见的遗传病因:目的:研究 PKD 的临床和遗传特征,并建立基因型与表型之间的相关性:我们招募了219名PKD患者,记录了他们的临床信息,并使用桑格测序法进行了PRRT2筛查。对49名没有PRRT2变异的PKD疑似患者进行了全外显子测序。结果显示,在219名PKD患者中(99人),PRRT2变异率为0.9%,而PKD患者的PRRT2变异率为0.9%:结果:在219例PKD患者中(99例来自39个家族,120例为散发性病例),发现了16个PRRT2变异。9个变异(c.879+4A>G、c.879+5G>A、c.856G>A、c.955G>T、c.884G>C、c.649C>T、c.649dupC、c.649delC和c.696697delCA),而 7 个是新发现的(c.367_403del、c.347_348delAA、c.835C>T、c.116dupC、c.837_838insC、c.916_937del 和 c.902G>A)。从发病到确诊的平均间隔时间为 7.94 年。与没有PRRT2变异体的患者相比,有变异体的患者更可能有阳性家族史,发病年龄更早,在治疗前发作时跌倒的发生率更高(分别为27.14%和8.99%)。具有截短PRRT2变异体的患者往往双侧发病。我们在两名PRRT2阴性的PKD患者中发现了两个跨膜蛋白151A(TMEM151A)变异体,包括一个新变异体(c.368G>C)和一个已报道的变异体(c.203C>T):这些发现为PKD患者的临床特征、诊断时限和治疗反应提供了启示。具有截短PRRT2变异的PKD患者可能会有更严重的阵发性症状。这项研究扩大了PRRT2和TMEM151A变体的范围。卡马西平和奥卡西平都是PKD患者的一线治疗选择。
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引用次数: 0
Tenecteplase for the treatment of acute ischemic stroke in the extended time window: a systematic review and meta-analysis 延长时间窗内治疗急性缺血性脑卒中的替奈普酶:系统综述和荟萃分析
IF 5.9 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-01-01 DOI: 10.1177/17562864231221324
L. Palaiodimou, A. Katsanos, Guillaume Turc, Michele Romoli, Aikaterini Theodorou, R. Lemmens, Simona Sacco, G. Velonakis, C. Vlachopoulos, G. Tsivgoulis
Background: Outcome data regarding the administration of tenecteplase (TNK) to acute ischemic stroke (AIS) patients presenting in the extended time window are limited. Objectives: We aimed to assess the current evidence regarding the efficacy and safety of TNK at a dose of 0.25 mg/kg for AIS treatment in the extended time window. Design: A systematic review and meta-analysis was conducted including all available randomized-controlled clinical trials (RCTs) that compared TNK 0.25 mg/kg versus no thrombolysis in AIS patients presenting in the extended time window (>4.5 h after last-seen-well or witnessed onset). Data sources and methods: Eligible studies were identified by searching Medline, Scopus, and international conference abstracts. The predefined efficacy outcomes of interest were 3-month excellent functional outcome [defined as the modified Rankin Scale (mRS) score ⩽1; primary outcome], 3-month good functional outcome (mRS ⩽ 2), 3-month reduced disability (⩾1-point reduction across all mRS scores). We determined symptomatic intracranial hemorrhage (sICH), any ICH and 3-month mortality as safety endpoints. A random-effects model was used to calculate risk ratios (RRs) and common odds ratios (cORs) with corresponding 95% confidence intervals (CIs). Results: Three RCTs were included comprising 556 patients treated with TNK versus 560 controls. TNK 0.25 mg/kg was associated with a higher likelihood of 3-month excellent functional outcome compared to controls (RR = 1.17; 95% CI = 1.01–1.36; I2 = 0%), whereas there was no difference regarding good functional outcome (RR = 1.05; 95% CI = 0.94–1.17; I2 = 0%) and reduced disability (adjusted cOR = 1.14; 95% CI = 0.92–1.40; I2 = 0%) at 3 months. The risks of sICH (RR = 1.67; 95% CI = 0.70–4.00; I2 = 0%), any ICH (RR = 1.08; 95% CI = 0.90–1.29; I2 = 0%) and 3-month mortality (RR = 1.10; 95% CI = 0.81–1.49; I2 = 0%) were similar between the groups. Conclusion: Based on data from three RCTs showing increased efficacy and a favorable safety profile of TNK in the treatment of AIS in the extended time window, continuing efforts of ongoing RCTs in the field are clearly supported. Trial registration: PROSPERO registration ID: CRD42023448707.
背景:有关在延长时间窗内对急性缺血性卒中(AIS)患者使用替奈普酶(TNK)的结果数据有限。目的:我们旨在评估目前有关替奈普酶疗效的证据:我们的目的是评估目前有关 0.25 mg/kg 剂量的 TNK 在延长时间窗治疗 AIS 的有效性和安全性的证据。设计:我们进行了一项系统性回顾和荟萃分析,包括所有可用的随机对照临床试验(RCT),这些试验比较了 TNK 0.25 mg/kg 与不溶栓治疗在延长时间窗(最后一次见井或目击发病后 >4.5 小时)出现的 AIS 患者的效果。数据来源和方法:通过检索 Medline、Scopus 和国际会议摘要确定符合条件的研究。预定义的疗效结果为 3 个月的极佳功能结果[定义为改良 Rankin 量表(mRS)评分⩽1;主要结果]、3 个月的良好功能结果(mRS ⩽2)、3 个月的残疾程度降低(所有 mRS 评分均降低⩾1 分)。我们将症状性颅内出血(sICH)、任何 ICH 和 3 个月死亡率作为安全性终点。我们采用随机效应模型计算风险比 (RR) 和常见几率比 (cOR),并得出相应的 95% 置信区间 (CI)。结果:共纳入三项研究,包括556名接受TNK治疗的患者和560名对照组患者。与对照组相比,TNK 0.25 mg/kg与3个月的优良功能预后相关(RR = 1.17;95% CI = 1.01-1.36;I2 = 0%),而在3个月的优良功能预后(RR = 1.05;95% CI = 0.94-1.17;I2 = 0%)和残疾减少(调整后的cOR = 1.14;95% CI = 0.92-1.40;I2 = 0%)方面没有差异。各组间发生 sICH(RR = 1.67;95% CI = 0.70-4.00;I2 = 0%)、任何 ICH(RR = 1.08;95% CI = 0.90-1.29;I2 = 0%)和 3 个月死亡率(RR = 1.10;95% CI = 0.81-1.49;I2 = 0%)的风险相似。结论根据三项 RCT 的数据显示,TNK 在延长时间窗内治疗 AIS 的疗效增强,安全性良好,因此该领域正在进行的 RCT 显然得到了支持。试验注册:PROSPERO 注册号:CRD4202344870CRD42023448707。
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引用次数: 0
Guideline for the management of myasthenic syndromes. 肌萎缩综合征治疗指南。
IF 5.9 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2023-12-26 eCollection Date: 2023-01-01 DOI: 10.1177/17562864231213240
Heinz Wiendl, Angela Abicht, Andrew Chan, Adela Della Marina, Tim Hagenacker, Khosro Hekmat, Sarah Hoffmann, Hans-Stefan Hoffmann, Sebastian Jander, Christian Keller, Alexander Marx, Arthur Melms, Nico Melzer, Wolfgang Müller-Felber, Marc Pawlitzki, Jens-Carsten Rückert, Christiane Schneider-Gold, Benedikt Schoser, Bettina Schreiner, Michael Schroeter, Bettina Schubert, Jörn-Peter Sieb, Fritz Zimprich, Andreas Meisel

Myasthenia gravis (MG), Lambert-Eaton myasthenic syndrome (LEMS), and congenital myasthenic syndromes (CMS) represent an etiologically heterogeneous group of (very) rare chronic diseases. MG and LEMS have an autoimmune-mediated etiology, while CMS are genetic disorders. A (strain dependent) muscle weakness due to neuromuscular transmission disorder is a common feature. Generalized MG requires increasingly differentiated therapeutic strategies that consider the enormous therapeutic developments of recent years. To include the newest therapy recommendations, a comprehensive update of the available German-language guideline 'Diagnostics and therapy of myasthenic syndromes' has been published by the German Neurological society with the aid of an interdisciplinary expert panel. This paper is an adapted translation of the updated and partly newly developed treatment guideline. It defines the rapid achievement of complete disease control in myasthenic patients as a central treatment goal. The use of standard therapies, as well as modern immunotherapeutics, is subject to a staged regimen that takes into account autoantibody status and disease activity. With the advent of modern, fast-acting immunomodulators, disease activity assessment has become pivotal and requires evaluation of the clinical course, including severity and required therapies. Applying MG-specific scores and classifications such as Myasthenia Gravis Activities of Daily Living, Quantitative Myasthenia Gravis, and Myasthenia Gravis Foundation of America allows differentiation between mild/moderate and (highly) active (including refractory) disease. Therapy decisions must consider age, thymic pathology, antibody status, and disease activity. Glucocorticosteroids and the classical immunosuppressants (primarily azathioprine) are the basic immunotherapeutics to treat mild/moderate to (highly) active generalized MG/young MG and ocular MG. Thymectomy is indicated as a treatment for thymoma-associated MG and generalized MG with acetylcholine receptor antibody (AChR-Ab)-positive status. In (highly) active generalized MG, complement inhibitors (currently eculizumab and ravulizumab) or neonatal Fc receptor modulators (currently efgartigimod) are recommended for AChR-Ab-positive status and rituximab for muscle-specific receptor tyrosine kinase (MuSK)-Ab-positive status. Specific treatment for myasthenic crises requires plasmapheresis, immunoadsorption, or IVIG. Specific aspects of ocular, juvenile, and congenital myasthenia are highlighted. The guideline will be further developed based on new study results for other immunomodulators and biomarkers that aid the accurate measurement of disease activity.

重症肌无力(MG)、兰伯特-伊顿肌无力综合征(LEMS)和先天性肌无力综合征(CMS)是一组病因异构的(非常)罕见慢性疾病。MG 和 LEMS 的病因是自身免疫介导,而 CMS 则是遗传性疾病。神经肌肉传递障碍导致的(应变依赖性)肌无力是其共同特征。全身性 MG 需要越来越多的差异化治疗策略,并考虑到近年来治疗方面的巨大发展。为了纳入最新的治疗建议,德国神经病学协会在跨学科专家小组的协助下,对现有的德语指南《肌无力综合征的诊断和治疗》进行了全面更新。本文是对更新版和部分新制定的治疗指南的改编翻译。该指南将肌无力患者迅速实现疾病完全控制作为治疗的核心目标。标准疗法和现代免疫疗法的使用应根据自身抗体状态和疾病活动情况分阶段进行。随着现代速效免疫调节剂的出现,疾病活动性评估变得至关重要,需要对临床病程(包括严重程度和所需疗法)进行评估。应用MG专用评分和分类,如日常生活活动肌无力、定量肌无力和美国肌无力基金会,可以区分轻度/中度和(高度)活动性(包括难治性)疾病。治疗决策必须考虑年龄、胸腺病理、抗体状态和疾病活动性。糖皮质激素和经典免疫抑制剂(主要是硫唑嘌呤)是治疗轻度/中度至(高度)活动性全身性 MG/幼年 MG 和眼部 MG 的基本免疫疗法。胸腺切除术适用于治疗胸腺肿瘤相关性 MG 和乙酰胆碱受体抗体(AChR-Ab)阳性的全身性 MG。对于乙酰胆碱受体抗体(AChR-Ab)阳性的(高度)活动性全身性 MG,建议使用补体抑制剂(目前为 eculizumab 和 ravulizumab)或新生儿 Fc 受体调节剂(目前为 efgartigimod);对于肌肉特异性受体酪氨酸激酶(MuSK)-Ab 阳性的 MG,建议使用利妥昔单抗。肌无力危象的特殊治疗需要进行浆细胞分离、免疫吸附或静脉注射免疫球蛋白。本指南还强调了眼肌型、幼年型和先天性肌无力症的具体治疗方法。该指南将根据其他免疫调节剂和有助于准确测量疾病活动性的生物标志物的新研究结果进一步完善。
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引用次数: 0
Late-onset stiff-person syndrome: challenges in diagnosis and management. 晚发僵人综合征:诊断和管理方面的挑战。
IF 5.9 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2023-12-25 eCollection Date: 2023-01-01 DOI: 10.1177/17562864231214315
Marinos C Dalakas, Jessica Yi

Background: Stiff person syndrome (SPS) is a rare slowly progressive autoimmune neuronal hyperexcitability disease with very-high GAD-65 antibody titers that most commonly presents above the age of 20, with muscle stiffness, painful muscle spasms, slow gait, and falls leading to disability. In other autoimmune disorders, late-onset disease has different symptom-spectrum and outcomes, but there is no information regarding late-onset SPS (LOSPS).

Objective: Highlight delayed diagnosis and poor tolerance or incomplete response to therapies of patients with LOSPS and outline how best to increase disease awareness early at onset.

Design a retrospective chart reviewmethods: We reviewed GAD-positive SPS patients with symptom onset above age 60, identified among 54 SPS patients, examined, treated and followed-up by the same clinicians, focused on clinical presentation, misdiagnoses, response and tolerance to therapies, and evolved disability.

Results: Nine patients had LOSPS with symptom onset at median age of 61 years (range 60-78), and current median age of 73. The median time from symptom onset to SPS diagnosis was 3 years; prior to diagnosis, five patients were treated for lumbosacral radiculopathies (one with laminectomy), two for Parkinson's disease, one for multiple sclerosis, and another for cerebellar degeneration. Progressive decline occurred rapidly in all patients; at time of diagnosis, six patients were already using a cane or walker and two were wheelchair-bound. Tolerance and response to treatment were limited; two patients did not respond to IVIg, two discontinued IVIg despite early response due to comorbidities (cardiac disease, thrombosis), four others partially responded to IVIg and one to rituximab; several could not tolerate high doses of oral antispasmodics due to somnolence; and two patients died.

Conclusions: LOSPS is almost always misdiagnosed for other similar conditions commonly seen in the elderly. Patients with LOSPS decline quickly to clinically severe disease due to delayed treatment initiation, poor response or tolerance, other comorbidities, and possibly immunosenescence. Increased awareness that SPS can occur in the elderly mimicking other disorders is important for early diagnosis and treatment, even necessitating earlier immunotherapy initiation, compared to their younger counterparts, to prevent faster-evolving severe disability.

背景:僵人综合征(SPS)是一种罕见的缓慢进展性自身免疫性神经元过度兴奋疾病,GAD-65抗体滴度非常高,最常见于20岁以上,表现为肌肉僵硬、肌肉痉挛疼痛、步态缓慢、跌倒导致残疾。在其他自身免疫性疾病中,晚发型疾病具有不同的症状谱和预后,但目前还没有关于晚发型 SPS(LOSPS)的信息。目的:强调晚发型 SPS 患者的诊断延迟、耐受性差或对治疗反应不完全,并概述如何在发病早期提高对疾病的认识:我们回顾了54名SPS患者中发病年龄在60岁以上的GAD阳性SPS患者,由相同的临床医生进行检查、治疗和随访,重点关注临床表现、误诊、对疗法的反应和耐受性以及逐渐发展的残疾:九名患者患有 LOSPS,发病年龄中位数为 61 岁(60-78 岁不等),目前年龄中位数为 73 岁。从症状出现到确诊为 SPS 的中位时间为 3 年;确诊前,5 名患者接受过腰骶部神经根病治疗(其中 1 人接受了椎板切除术),2 人接受过帕金森病治疗,1 人接受过多发性硬化治疗,还有 1 人接受过小脑变性治疗。所有患者的病情都在迅速恶化;确诊时,六名患者已经需要使用拐杖或助行器,两名患者需要坐轮椅。患者对治疗的耐受性和反应有限;两名患者对IVIg无反应,两名患者因合并症(心脏病、血栓)而在早期出现反应后停用了IVIg,另外四名患者对IVIg有部分反应,一名患者对利妥昔单抗有反应;几名患者因嗜睡而无法耐受大剂量口服解痉剂;两名患者死亡:结论:LOSPS几乎总是被误诊为其他常见于老年人的类似疾病。由于延迟开始治疗、反应差或耐受性差、其他并发症以及可能的免疫衰老,LOSPS 患者的病情很快恶化为临床重症。提高对 SPS 可模拟其他疾病发生在老年人身上的认识,对于早期诊断和治疗非常重要,甚至有必要比年轻人更早开始免疫治疗,以防止严重残疾的快速发展。
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引用次数: 0
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Therapeutic Advances in Neurological Disorders
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