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A novel de novo variant in POLR3B gene associated with a primary axonal involvement of the largest nerve fibers POLR3B基因的一种新的从头变异与最大神经纤维的原发性轴突受累有关。
IF 3.8 3区 医学 Q1 Medicine Pub Date : 2023-10-28 DOI: 10.1111/jns.12602
Alessandro Geroldi, Stefano Tozza, Chiara Fiorillo, Maria Nolano, Paola Fossa, Floriana Vitale, Regi Domi, Andrea Gaudio, Alessia Mammi, Serena Patrone, Andrea La Barbera, Paola Origone, Clarissa Ponti, Francesca Sanguineri, Federico Zara, Matteo Cataldi, Vincenzo Salpietro, Consuelo Barbara Venturi, Sara Massucco, Angelo Schenone, Fiore Manganelli, Paola Mandich, Emilia Bellone, Fabio Gotta

Background and Aims

POLR3B gene encodes a subunit of RNA polymerase III (Pol III). Biallelic mutations in POLR3B are associated with leukodystrophies, but recently de novo heterozygous mutations have been described in early onset peripheral demyelinating neuropathies with or without central involvement. Here, we report the first Italian case carrying a de novo variant in POLR3B with a pure neuropathy phenotype and primary axonal involvement of the largest nerve fibers.

Methods

Nerve conduction studies, sympathetic skin response, dynamic sweat test, tactile and thermal quantitative sensory testing and brain magnetic resonance imaging were performed according to standard procedures. Histopathological examination was performed on skin and sural nerve biopsies. Molecular analysis of the proband and his relatives was performed with Next Generation Sequencing. The impact of the identified variant on the overall protein structure was evaluated through rotamers method.

Results

Since his early adolescence, the patient presented with signs of polyneuropathy with severe distal weakness, atrophy, and reduced sensation. Neurophysiological studies showed a sensory-motor axonal polyneuropathy, with confirmed small fiber involvement. In addition, skin biopsy and sural nerve biopsy showed predominant large fibers involvement. A trio's whole exome sequencing revealed a novel de novo variant p.(Arg1046Cys) in POLR3B, which was classified as Probably Pathogenic. Molecular modeling data confirmed a deleterious effect of the variant on protein structure.

Interpretation

Neurophysiological and morphological findings suggest a primary axonal involvement of the largest nerve fibers in POLR3B-related neuropathies. A partial loss of function mechanism is proposed for both neuropathy and leukodystrophy phenotypes.

背景和目的:POLR3B基因编码RNA聚合酶III(Pol III)的一个亚基。POLR3B中的双等位基因突变与白细胞营养不良有关,但最近在伴有或不伴有中枢受累的早发性外周脱髓鞘神经病中描述了新发杂合突变。在这里,我们报道了意大利首例携带POLR3B从头变异的病例,该病例具有纯神经病变表型和最大神经纤维的原发性轴突受累。方法:按照标准程序进行神经传导研究、交感神经皮肤反应、动态汗液测试、触觉和热定量感觉测试以及脑MRI。对皮肤和腓肠神经活检进行组织病理学检查。先证者及其亲属的分子分析采用下一代测序法进行。通过轮调异构体方法评估鉴定的变体对整体蛋白质结构的影响。结果:自青少年早期以来,患者就表现出多发性神经病的症状,伴有严重的远端无力、萎缩和感觉减退。神经生理学研究显示一种感觉运动轴突多发性神经病,证实有小纤维受累。此外,皮肤活检和腓肠神经活检显示主要的大纤维受累。三人组的全外显子组测序(WES)揭示了POLR3B中一种新的从头变异p。(Arg1046Cys),被归类为可能致病。分子建模数据证实了该变体对蛋白质结构的有害影响。解释:神经生理学和形态学结果表明,POLR3B相关神经病中最大神经纤维的原发性轴突受累。神经病变和白细胞营养不良表型的部分功能丧失机制被提出。这篇文章受版权保护。保留所有权利。
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引用次数: 0
Unveiling the clinical and electrophysiological profile of CMTX6: Insights from two Brazilian families 揭示CMTX6的临床和电生理特征:来自两个巴西家族的见解。
IF 3.8 3区 医学 Q1 Medicine Pub Date : 2023-10-17 DOI: 10.1111/jns.12601
Victor Augusto Zanesi Maciel, Gustavo Maximiano-Alves, Rodrigo Siqueira Soares Frezatti, Anna Letícia De Moraes Alves, Bianca Mara Alves Andrade, Rita De Cassia Carvalho Leal, Pedro José Tomaselli, Mary M. Reilly, Wilson Marques
BACKGROUND AND AIMSX-linked Charcot-Marie-Tooth disease type 6 (CMTX6) is an extremely rare condition associated with mutations in the PDK3 gene. To date, only three families from different countries have been reported (Australia, South Korea and Germany). In this study, we sought to provide a comprehensive clinical and electrophysiological characterization of two Brazilian families.METHODSWe conducted comprehensive clinical assessments, extensive electrophysiological evaluations, and performed whole-exome sequencing in the probands to investigate the genetic basis of the disease.RESULTSMales in the family carrying the Arg162His mutation displayed early-onset motor and/or sensory axonal neuropathy, absence of tendon jerks, pes cavus, and frequently reported pain. Females in the same family exhibited a milder phenotype of the disease with later onset and some remained asymptomatic into their 50s. In the unrelated family with a single affected male, the clinical presentation was characterized by severe progressive sensorimotor polyneuropathy accompanied by neuropathic pain.INTERPRETATIONWe report two Brazilian families with CMTX6 including one harboring a previously unpublished variant in the PDK3 gene, which co-segregates with the disease as expected in a X-linked disease. Notably, the clinical presentations across the five families with available descriptions, including our study, share striking similarities. Furthermore, the proximity of the three reported mutations suggests potential functional similarities and common underlying mechanisms. This study contributes to the growing knowledge of CMTX6 and underscores the importance of international collaborations in studying rare genetic disorders. This article is protected by copyright. All rights reserved.
背景和目的:6型X连锁Charcot-Marie Tooth病(CMTX6)是一种极为罕见的与PDK3基因突变有关的疾病。迄今为止,只报告了来自不同国家的三个家庭(澳大利亚、韩国和德国)。在这项研究中,我们试图提供两个巴西家庭的全面临床和电生理特征。方法:我们对先证者进行了全面的临床评估、广泛的电生理评估,并进行了全外显子组测序,以研究该疾病的遗传基础。结果:携带Arg162His突变的家族中的男性表现出早发性运动和/或感觉轴索神经病变,没有肌腱痉挛、空腔炎和经常报告的疼痛。同一家族的女性表现出较温和的疾病表型,发病较晚,一些女性在50多岁时仍无症状。在有一名患病男性的无关家族中,临床表现为严重的进行性感觉运动性多发性神经病伴神经性疼痛。解释:我们报道了两个患有CMTX6的巴西家族,其中一个家族在PDK3基因中携带一个先前未发表的变体,该变体与X连锁疾病中预期的疾病共分离。值得注意的是,包括我们的研究在内的五个有可用描述的家族的临床表现有着惊人的相似之处。此外,报告的三种突变的接近性表明了潜在的功能相似性和共同的潜在机制。这项研究有助于增加对CMTX6的了解,并强调了国际合作在研究罕见遗传疾病方面的重要性。这篇文章受版权保护。保留所有权利。
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引用次数: 0
Identification of blood metabolic biomarkers associated with diabetic distal symmetric sensorimotor polyneuropathy in patients with type 2 diabetes mellitus 2型糖尿病患者中与糖尿病远端对称性感觉运动多发性神经病相关的血液代谢生物标志物的鉴定。
IF 3.8 3区 医学 Q1 Medicine Pub Date : 2023-10-13 DOI: 10.1111/jns.12600
Kuo-Hsuan Chang, Chiung-Mei Chen, Chia-Ni Lin, Sung-Sheng Tsai, Rong-Kuo Lyu, Chun-Che Chu, Long-Sun Ro, Ming-Feng Liao, Hong-Shiu Chang, Yi-Ching Weng, Jawl-Shan Hwang, Hung-Chou Kuo

Background

Distal symmetric sensorimotor polyneuropathy (DSPN) is a common neurologic complication of type 2 diabetes mellitus (T2DM), but the underlying mechanisms and changes in serum metabolites remain largely undefined. This study aimed to characterize the plasma metabolite profiles of participants with T2DM using targeted metabolomics analysis and identify potential biomarkers for DSPN.

Methods

A combined liquid chromatography MS/MS and direct flow injection were used to quantify plasma metabolite obtained from 63 participants with T2DM, 81 with DSPN, and 33 nondiabetic control participants. A total of 130 metabolites, including amino acids, biogenic amines, sphingomyelins (SM), phosphatidylcholines, carnitines, and hexose, were analyzed.

Results

A total of 16 plasma metabolites and 3 cholesterol-related laboratory parameters were found to have variable importance in the projection score >1.0 and false discovery rate <5.0% between control, T2DM, and DSPN. Among these variables, five serum metabolites, including phenylalanine (AUC = 0.653), alanine (AUC = 0.630), lysine (AUC = 0.622) tryptophan (AUC = 0.620), and SM C16:0 (AUC = 0.630), are potential biomarkers (all p < .05) in distinguishing T2DM with DSPN from those without (AUC = 0.720).

Conclusions

In this cross-sectional study, derangement of several metabolites in the plasma was observed in T2DM with and without DSPN, and these metabolites may be potential biomarkers for predicting DSPN. Longitudinal studies are warranted.

背景:远端对称性感觉运动性多发性神经病(DSPN)是2型糖尿病(T2DM)常见的神经并发症,但其潜在机制和血清代谢产物的变化在很大程度上尚不清楚。本研究旨在通过靶向代谢组学分析来表征T2DM参与者的血浆代谢产物谱,并确定DSPN的潜在生物标志物。方法:采用液相色谱MS/MS和直接流式注射相结合的方法对63名T2DM患者、81名DSPN患者和33名非糖尿病对照组患者的血浆代谢产物进行定量。共分析了130种代谢产物,包括氨基酸、生物胺、鞘磷脂(SM)、磷脂酰胆碱、肉碱和己糖。结果:共发现16种血浆代谢物和3种胆固醇相关实验室参数在预测得分中具有可变重要性> 1.0和错误发现率结论:在这项横断面研究中,在有和没有DSPN的T2DM患者中观察到血浆中几种代谢产物的紊乱,这些代谢产物可能是预测DSPN的潜在生物标志物。有必要进行纵向研究。这篇文章受版权保护。保留所有权利。
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引用次数: 0
European Academy of Neurology/Peripheral Nerve Society Guideline on diagnosis and treatment of Guillain–Barré syndrome 欧洲神经病学学会/外周神经学会格林-巴利综合征诊断和治疗指南。
IF 3.8 3区 医学 Q1 Medicine Pub Date : 2023-10-10 DOI: 10.1111/jns.12594
Pieter A. van Doorn, Peter Y. K. Van den Bergh, Robert D. M. Hadden, Bert Avau, Patrik Vankrunkelsven, Shahram Attarian, Patricia H. Blomkwist-Markens, David R. Cornblath, H. Stephan Goedee, Thomas Harbo, Bart C. Jacobs, Susumu Kusunoki, Helmar C. Lehmann, Richard A. Lewis, Michael P. Lunn, Eduardo Nobile-Orazio, Luis Querol, Yusuf A. Rajabally, Thirugnanam Umapathi, Haluk A. Topaloglu, Hugh J. Willison

Guillain–Barré syndrome (GBS) is an acute polyradiculoneuropathy. Symptoms may vary greatly in presentation and severity. Besides weakness and sensory disturbances, patients may have cranial nerve involvement, respiratory insufficiency, autonomic dysfunction and pain. To develop an evidence-based guideline for the diagnosis and treatment of GBS, using Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology, a Task Force (TF) of the European Academy of Neurology (EAN) and the Peripheral Nerve Society (PNS) constructed 14 Population/Intervention/Comparison/Outcome questions (PICOs) covering diagnosis, treatment and prognosis of GBS, which guided the literature search. Data were extracted and summarised in GRADE Summaries of Findings (for treatment PICOs) or Evidence Tables (for diagnostic and prognostic PICOs). Statements were prepared according to GRADE Evidence-to-Decision (EtD) frameworks. For the six intervention PICOs, evidence-based recommendations are made. For other PICOs, good practice points (GPPs) are formulated. For diagnosis, the principal GPPs are: GBS is more likely if there is a history of recent diarrhoea or respiratory infection; CSF examination is valuable, particularly when the diagnosis is less certain; electrodiagnostic testing is advised to support the diagnosis; testing for anti-ganglioside antibodies is of limited clinical value in most patients with typical motor-sensory GBS, but anti-GQ1b antibody testing should be considered when Miller Fisher syndrome (MFS) is suspected; nodal–paranodal antibodies should be tested when autoimmune nodopathy is suspected; MRI or ultrasound imaging should be considered in atypical cases; and changing the diagnosis to acute-onset chronic inflammatory demyelinating polyradiculoneuropathy (A-CIDP) should be considered if progression continues after 8 weeks from onset, which occurs in around 5% of patients initially diagnosed with GBS. For treatment, the TF recommends intravenous immunoglobulin (IVIg) 0.4 g/kg for 5 days, in patients within 2 weeks (GPP also within 2–4 weeks) after onset of weakness if unable to walk unaided, or a course of plasma exchange (PE) 12–15 L in four to five exchanges over 1–2 weeks, in patients within 4 weeks after onset of weakness if unable to walk unaided. The TF recommends against a second IVIg course in GBS patients with a poor prognosis; recommends against using oral corticosteroids, and weakly recommends against using IV corticosteroids; does not recommend PE followed immediately by IVIg; weakly recommends gabapentinoids, tricyclic antidepressants or carbamazepine for treatment of pain; does not recommend a specific treatment for fatigue. To estimate the prognosis of individual patients, the TF advises using the modified Erasmus GBS outcome score (mEGOS) to assess outcome, and the modified Erasmus GBS Respiratory Insufficiency Score (mEGRIS) to assess the risk of requiring artificial ventilation. Based on the PICOs, available

格林-巴利综合征(GBS)是一种急性多神经根性神经病。症状的表现和严重程度可能有很大差异。除了虚弱和感觉障碍外,患者还可能有脑神经受累、呼吸功能不全、自主神经功能障碍和疼痛。为了制定GBS诊断和治疗的循证指南,使用建议、评估、发展和评估分级(GRADE)方法,欧洲神经病学学会(EAN)和周围神经学会(PNS)的一个工作组(TF)构建了14个群体/干预/比较/结果问题(PICO),涵盖GBS的诊断、治疗和预后,指导了文献检索。数据被提取并汇总在GRADE发现总结(用于治疗PICO)或证据表(用于诊断和预后PICO)中。根据GRADE决策证据(EtD)框架编制报表。对于六个干预PICO,提出了基于证据的建议。对于其他PICO,制定了良好实践要点。就诊断而言,主要的GP是:如果最近有腹泻或呼吸道感染史,GBS更有可能发生;脑脊液检查是有价值的,尤其是当诊断不太确定时;建议使用电诊断测试来支持诊断;抗神经节苷脂抗体检测在大多数典型运动感觉GBS患者中的临床价值有限,但当怀疑Miller Fisher综合征(MFS)时,应考虑抗GQ1b抗体检测;当怀疑自身免疫性多巴胺时,应检测淋巴结旁抗体;非典型病例应考虑MRI或超声成像;如果8年后病情继续恶化,应考虑将诊断改为急性发作的慢性炎症性脱髓鞘多神经根病变(A-CID) 发病数周后,约5%的最初诊断为GBS的患者出现这种情况。对于治疗,TF建议静脉注射免疫球蛋白(IVIg)0.4 g/kg,适用于5 天,患者在2天内 周(GPP也在2-4内 数周),如果无法独立行走,或进行血浆置换(PE)12-15 L在四到五次交换中超过1-2 周,患者在4周内 虚弱发作后数周,如果无法独立行走。TF建议在预后不良的GBS患者中不要进行第二次IVIg疗程;建议不要使用口服皮质类固醇,并强烈建议不要使用静脉注射皮质类固醇;不建议PE后立即IVIg;弱推荐加巴喷丁类、三环类抗抑郁药或卡马西平用于治疗疼痛;不建议对疲劳进行特殊治疗。为了评估个别患者的预后,TF建议使用改良的伊拉斯谟GBS结果评分(mEGOS)来评估结果,并使用改良的埃拉斯谟-GBS呼吸功能不全评分(mEG RIS)来评估需要人工通气的风险。根据PICO、现有文献和其他讨论,我们提供了流程图,以帮助做出诊断、治疗和重症监护室入院需求的临床决策。
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引用次数: 0
PNS Abstracts 2023 PNS摘要2023
IF 3.8 3区 医学 Q1 Medicine Pub Date : 2023-10-09 DOI: 10.1111/jns.12585
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引用次数: 0
Mutational screening of Greek patients with axonal Charcot-Marie-Tooth disease using targeted next-generation sequencing: Clinical and molecular spectrum delineation 使用靶向下一代测序对希腊轴索性Charcot-Marie Tooth病患者进行突变筛查:临床和分子谱描绘。
IF 3.8 3区 医学 Q1 Medicine Pub Date : 2023-09-25 DOI: 10.1111/jns.12598
Zoi Kontogeorgiou, Chrisoula Kartanou, Michail Rentzos, Panagiotis Kokotis, Evangelos Anagnostou, Thomas Zambelis, Elisabeth Chroni, Argyris Dinopoulos, Marios Panas, Georgios Koutsis, Georgia Karadima

Background and Aims

Axonal forms of Charcot-Marie-Tooth disease (CMT) are classified as CMT2, distal hereditary motor neuropathy (dHMN) or hereditary sensory neuropathy (HSN) and can be caused by mutations in over 100 genes. We presently aimed to investigate for the first time the genetic landscape of axonal CMT in the Greek population.

Methods

Sixty index patients with CMT2, dHMN or HSN were screened by a combination of Sanger sequencing (GJB1) and next-generation sequencing custom-made gene panel covering 24 commonly mutated genes in axonal CMT.

Results

Overall, 20 variants classified as pathogenic or likely pathogenic were identified in heterozygous state in 20 index cases, representing 33.3% of the cohort. Of these, 14 were known pathogenic/likely pathogenic and six were designated as such according to ACMG classification, after in silico evaluation, testing for familial segregation and further literature review. The most frequently involved genes were GJB1 (11.7%), MPZ (5%) and MFN2 (5%), followed by DNM2 (3.3%) and LRSAM1 (3.3%). Single cases were identified with mutations in BSCL2, HSPB1 and GDAP1.

Interpretation

A wide phenotypic variability in terms of severity and age of onset was noted. Given the limited number of genes tested, the diagnostic yield of the present panel compares favourably with studies in other European populations. Our study delineates the genetic and phenotypic variability of inherited axonal neuropathies in the Greek population and contributes to the pathogenicity characterization of further variants linked to axonal neuropathies.

背景和目的:Charcot-Marie Tooth病(CMT)的轴索型分为CMT2、远端遗传性运动神经病(dHMN)或遗传性感觉神经病(HSN),可由100多个基因突变引起。我们目前的目标是首次调查希腊人群中轴突CMT的遗传景观。方法:采用Sanger测序(GJB1)和下一代测序定制基因组相结合的方法对60例CMT2、dHMN或HSN指数患者进行筛选,该基因组涵盖了轴突CMT中24个常见突变基因。其中,14例为已知致病性/可能致病性,6例根据ACMG分类,经过计算机评估、家族分离测试和进一步的文献综述后被指定为已知致病/可能致病。最常见的相关基因是GJB1(11.7%)、MPZ(5%)和MFN2(5%),其次是DNM2(3.3%)和LRSAM1(3.3%)。单个病例被鉴定为BSCL2、HSPB1和GDAP1突变。解释:在严重程度和发病年龄方面存在广泛的表型变异。鉴于测试的基因数量有限,本小组的诊断结果与其他欧洲人群的研究相比是有利的。我们的研究描述了希腊人群中遗传性轴索神经病的遗传和表型变异性,并有助于与轴索神经病相关的进一步变异的致病性表征。
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引用次数: 0
Diagnostic value of nerve conduction study in NOTCH2NLC-related neuronal intranuclear inclusion disease 神经传导研究对NOTCH2NLC相关神经元核内包涵体疾病的诊断价值。
IF 3.8 3区 医学 Q1 Medicine Pub Date : 2023-09-25 DOI: 10.1111/jns.12599
Yun Tian, Xuan Hou, Wanqian Cao, Lu Zhou, Bin Jiao, Sizhe Zhang, Qiao Xiao, Jin Xue, Ying Wang, Ling Weng, Liangjuan Fang, Honglan Yang, Yafang Zhou, Fang Yi, Xiaoyu Chen, Juan Du, Qian Xu, Li Feng, Zhenhua Liu, Sen Zeng, Qiying Sun, Nina Xie, Mengchuan Luo, Mengli Wang, Mengqi Zhang, Qiuming Zeng, Shunxiang Huang, Lingyan Yao, Yacen Hu, Hongyu Long, Yuanyuan Xie, Si Chen, Qing Huang, Junpu Wang, Bin Xie, Lin Zhou, Lili Long, Jifeng Guo, Junling Wang, Xinxiang Yan, Hong Jiang, Hongwei Xu, Ranhui Duan, Beisha Tang, Ruxu Zhang, Lu Shen

Background and Aims

Neuronal intranuclear inclusion disease (NIID) is a rare progressive neurodegenerative disorder mainly caused by abnormally expanded GGC repeats within the NOTCH2NLC gene. Most patients with NIID show polyneuropathy. Here, we aim to investigate diagnostic electrophysiological markers of NIID.

Methods

In this retrospective dual-center study, we reviewed 96 patients with NOTCH2NLC-related NIID, 94 patients with genetically confirmed Charcot–Marie-Tooth (CMT) disease, and 62 control participants without history of peripheral neuropathy, who underwent nerve conduction studies between 2018 and 2022.

Results

Peripheral nerve symptoms were presented by 53.1% of patients with NIID, whereas 97.9% of them showed peripheral neuropathy according to electrophysiological examinations. Patients with NIID were characterized by slight demyelinating sensorimotor polyneuropathy; some patients also showed mild axonal lesions. Motor nerve conduction velocity (MCV) of the median nerve usually exceeded 35 m/s, and were found to be negatively correlated with the GGC repeat sizes. Regarding the electrophysiological differences between muscle weakness type (n = 27) and non-muscle weakness type (n = 69) of NIID, nerve conduction abnormalities were more severe in the muscle weakness type involving both demyelination and axonal impairment. Notably, specific DWI subcortical lace sign was presented in only 33.3% of muscle weakness type, thus it was difficult to differentiate them from CMT. Combining age of onset, distal motor latency, and compound muscle action potential of the median nerve showed the optimal diagnostic performance to distinguish NIID from major CMT (AUC = 0.989, sensitivity = 92.6%, specificity = 97.4%).

Interpretation

Peripheral polyneuropathy is common in NIID. Our study suggest that nerve conduction study is useful to discriminate NIID.

背景和目的:神经元核内包涵体病(NIID)是一种罕见的进行性神经退行性疾病,主要由NOTCH2NLC基因内GGC重复序列异常扩增引起。大多数NIID患者表现为多发性神经病。在这里,我们的目的是研究NIID的诊断电生理标志物。方法:在这项回顾性双中心研究中,我们回顾了96名NOTCH2NLC相关NIID患者、94名遗传证实的Charcot-Marie Tooth(CMT)疾病患者和62名无周围神经病变史的对照参与者,他们在2018年至2022年间接受了神经传导研究。结果:53.1%的NIID患者出现了周围神经症状,而根据电生理检查,97.9%的患者表现为周围神经病变。NIID患者的特点是轻度脱髓鞘感觉运动性多发性神经病;一些患者还表现出轻微的轴索损伤。正中神经的运动神经传导速度(MCV)通常超过35 m/s,并且被发现与GGC重复大小呈负相关。关于肌无力类型(n = 27)和非肌无力型(n = 69),神经传导异常在涉及脱髓鞘和轴突损伤的肌无力型中更为严重。值得注意的是,只有33.3%的肌无力类型出现了特定的DWI皮质下系带征,因此很难将其与CMT区分开来。结合发病年龄、远端运动潜伏期和正中神经的复合肌肉动作电位,显示出区分NIID和主要CMT的最佳诊断性能(AUC = 0.989,灵敏度 = 92.6%,特异性 = 97.4%)。解释:周围性多发性神经病在NIID中很常见。我们的研究表明,神经传导研究有助于鉴别NIID。
{"title":"Diagnostic value of nerve conduction study in NOTCH2NLC-related neuronal intranuclear inclusion disease","authors":"Yun Tian,&nbsp;Xuan Hou,&nbsp;Wanqian Cao,&nbsp;Lu Zhou,&nbsp;Bin Jiao,&nbsp;Sizhe Zhang,&nbsp;Qiao Xiao,&nbsp;Jin Xue,&nbsp;Ying Wang,&nbsp;Ling Weng,&nbsp;Liangjuan Fang,&nbsp;Honglan Yang,&nbsp;Yafang Zhou,&nbsp;Fang Yi,&nbsp;Xiaoyu Chen,&nbsp;Juan Du,&nbsp;Qian Xu,&nbsp;Li Feng,&nbsp;Zhenhua Liu,&nbsp;Sen Zeng,&nbsp;Qiying Sun,&nbsp;Nina Xie,&nbsp;Mengchuan Luo,&nbsp;Mengli Wang,&nbsp;Mengqi Zhang,&nbsp;Qiuming Zeng,&nbsp;Shunxiang Huang,&nbsp;Lingyan Yao,&nbsp;Yacen Hu,&nbsp;Hongyu Long,&nbsp;Yuanyuan Xie,&nbsp;Si Chen,&nbsp;Qing Huang,&nbsp;Junpu Wang,&nbsp;Bin Xie,&nbsp;Lin Zhou,&nbsp;Lili Long,&nbsp;Jifeng Guo,&nbsp;Junling Wang,&nbsp;Xinxiang Yan,&nbsp;Hong Jiang,&nbsp;Hongwei Xu,&nbsp;Ranhui Duan,&nbsp;Beisha Tang,&nbsp;Ruxu Zhang,&nbsp;Lu Shen","doi":"10.1111/jns.12599","DOIUrl":"10.1111/jns.12599","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Neuronal intranuclear inclusion disease (NIID) is a rare progressive neurodegenerative disorder mainly caused by abnormally expanded GGC repeats within the <i>NOTCH2NLC</i> gene. Most patients with NIID show polyneuropathy. Here, we aim to investigate diagnostic electrophysiological markers of NIID.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this retrospective dual-center study, we reviewed 96 patients with <i>NOTCH2NLC</i>-related NIID, 94 patients with genetically confirmed Charcot–Marie-Tooth (CMT) disease, and 62 control participants without history of peripheral neuropathy, who underwent nerve conduction studies between 2018 and 2022.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Peripheral nerve symptoms were presented by 53.1% of patients with NIID, whereas 97.9% of them showed peripheral neuropathy according to electrophysiological examinations. Patients with NIID were characterized by slight demyelinating sensorimotor polyneuropathy; some patients also showed mild axonal lesions. Motor nerve conduction velocity (MCV) of the median nerve usually exceeded 35 m/s, and were found to be negatively correlated with the GGC repeat sizes. Regarding the electrophysiological differences between muscle weakness type (<i>n</i> = 27) and non-muscle weakness type (<i>n</i> = 69) of NIID, nerve conduction abnormalities were more severe in the muscle weakness type involving both demyelination and axonal impairment. Notably, specific DWI subcortical lace sign was presented in only 33.3% of muscle weakness type, thus it was difficult to differentiate them from CMT. Combining age of onset, distal motor latency, and compound muscle action potential of the median nerve showed the optimal diagnostic performance to distinguish NIID from major CMT (AUC = 0.989, sensitivity = 92.6%, specificity = 97.4%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Peripheral polyneuropathy is common in NIID. Our study suggest that nerve conduction study is useful to discriminate NIID.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41124576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Management of Guillain–Barré syndrome in Bangladesh: Clinical practice, limitations and recommendations for low- and middle-income countries 孟加拉国格林-巴利综合征的治疗:低收入和中等收入国家的临床实践、局限性和建议。
IF 3.8 3区 医学 Q1 Medicine Pub Date : 2023-09-12 DOI: 10.1111/jns.12597
Nowshin Papri, Zhahirul Islam, Gulshan Ara, Tamal Saha, Sonja E. Leonhard, Hubert P. Endtz, Bart C. Jacobs, Quazi D. Mohammad

Background and Aims

Considerable variation in clinical practice for management of Guillain-Barré syndrome (GBS) has been observed worldwide. Diagnosis and treatment are challenging in low- and middle-income countries (LMIC) due to lack of facilities and treatment availability. We aimed to evaluate current clinical practice and limitations and to provide recommendation for GBS management in low-resource settings.

Methods

We conducted an explanatory-sequential mixed-methods survey among neurologists and internists working in tertiary and secondary government hospitals in Bangladesh. There were two phases: (1) quantitative (cross-sectional survey to evaluate clinical practice and limitations); (2) qualitative (key informant interview to explain certain clinical practice and provide recommendations for GBS management in LMIC). Data were analyzed by frequencies, χ2 test and thematic analysis.

Results

Among 159 physicians (65 neurologists and 94 internists), 11% and 8% physicians used Brighton and NINDS criteria respectively to diagnose GBS. Specific treatment protocols of GBS were used by 12% physicians. Overcrowding of patients, inadequate diagnostic facilities, high costs of standard therapy, and inadequate logistics and trained personnel for intensive care unit and rehabilitation services were considered major challenges for GBS management. In qualitative part, respondents recommended regular training for the physicians, development of cost-effective treatment strategies and appropriate patients' referral and management guideline considering existing limitations in health service delivery and socio-economic status of the country.

Interpretation

Current study design and recommendations might be applied for other LMIC. Such data can assist policymakers to identify areas requiring urgent attention and take required action to improve GBS management in LMIC.

背景和目的:在全球范围内,格林-巴利综合征(GBS)的临床实践存在相当大的差异。由于缺乏设施和治疗,中低收入国家的诊断和治疗具有挑战性。我们旨在评估当前的临床实践和局限性,并为低资源环境下的GBS管理提供建议。方法:我们对孟加拉国三级和二级政府医院的神经科医生和内科医生进行了解释性顺序混合方法调查。分为两个阶段:(1)定量(横断面调查,以评估临床实践和局限性);(2) 定性(关键信息者访谈,解释某些临床实践,并为LMIC的GBS管理提供建议)。采用频率、χ2检验和专题分析等方法对数据进行分析。结果:在159名医生(65名神经科医生和94名内科医生)中,11%和8%的医生分别使用Brighton和NINDS标准诊断GBS。12%的医生使用了GBS的特定治疗方案。患者过度拥挤、诊断设施不足、标准治疗成本高昂、重症监护室和康复服务的后勤和训练有素的人员不足被认为是GBS管理面临的主要挑战。在质量部分,受访者建议对医生进行定期培训,制定具有成本效益的治疗策略,并考虑到该国医疗服务提供和社会经济地位方面的现有限制,制定适当的患者转诊和管理指南。解释:目前的研究设计和建议可能适用于其他LMIC。这些数据可以帮助决策者确定需要紧急关注的领域,并采取必要行动改善LMIC的GBS管理。
{"title":"Management of Guillain–Barré syndrome in Bangladesh: Clinical practice, limitations and recommendations for low- and middle-income countries","authors":"Nowshin Papri,&nbsp;Zhahirul Islam,&nbsp;Gulshan Ara,&nbsp;Tamal Saha,&nbsp;Sonja E. Leonhard,&nbsp;Hubert P. Endtz,&nbsp;Bart C. Jacobs,&nbsp;Quazi D. Mohammad","doi":"10.1111/jns.12597","DOIUrl":"10.1111/jns.12597","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Considerable variation in clinical practice for management of Guillain-Barré syndrome (GBS) has been observed worldwide. Diagnosis and treatment are challenging in low- and middle-income countries (LMIC) due to lack of facilities and treatment availability. We aimed to evaluate current clinical practice and limitations and to provide recommendation for GBS management in low-resource settings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted an explanatory-sequential mixed-methods survey among neurologists and internists working in tertiary and secondary government hospitals in Bangladesh. There were two phases: (1) quantitative (cross-sectional survey to evaluate clinical practice and limitations); (2) qualitative (key informant interview to explain certain clinical practice and provide recommendations for GBS management in LMIC). Data were analyzed by frequencies, χ<sup>2</sup> test and thematic analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 159 physicians (65 neurologists and 94 internists), 11% and 8% physicians used Brighton and NINDS criteria respectively to diagnose GBS. Specific treatment protocols of GBS were used by 12% physicians. Overcrowding of patients, inadequate diagnostic facilities, high costs of standard therapy, and inadequate logistics and trained personnel for intensive care unit and rehabilitation services were considered major challenges for GBS management. In qualitative part, respondents recommended regular training for the physicians, development of cost-effective treatment strategies and appropriate patients' referral and management guideline considering existing limitations in health service delivery and socio-economic status of the country.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Current study design and recommendations might be applied for other LMIC. Such data can assist policymakers to identify areas requiring urgent attention and take required action to improve GBS management in LMIC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10214420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Nodal–paranodal antibodies in HIV-immune mediated radiculo-neuropathies: Clinical phenotypes and relevance HIV免疫介导的神经根性神经病中的结节旁抗体:临床表型和相关性。
IF 3.8 3区 医学 Q1 Medicine Pub Date : 2023-09-07 DOI: 10.1111/jns.12596
K. Moodley, V. B. Patel, A. A. Moodley, P. L. A. Bill, A. Kajee, V. Mgbachi, J. Fehmi, S. Rinaldi

Background

The frequency of nodal–paranodal antibodies in HIV-infected patients with chronic immune-mediated radiculo-neuropathies (IMRN) has not been previously described.

Methods

HIV-infected patients who met the inclusion criteria for chronic IMRN were screened for immunoglobulin G (IgG) antibodies directed against nodal (neurofascin (NF)186) and paranodal (NF155, contactin-1 (CNTN1) and contactin-associated protein(Caspr1)) cell adhesion molecules, using a live, cell-based assay.

To explore potential pathogenicity, binding of human IgG to myelinated co-cultures was assessed by incubation with patients' sera positive for nodal or paranodal antibodies. Normal human serum was added as a source of complement to assess for complement activation as a mechanism for myelin injury.

Results

Twenty-four HIV-infected patients with IMRN were included in the study, 15 with chronic inflammatory demyelinating polyneuropathy (CIDP), 4 with ventral root radiculopathies (VRR), and 5 with dorsal root ganglionopathies (DRG). Five patients with CIDP had combined central and peripheral demyelination (CCPD). Three patients (12.7%) tested positive for neurofascin IgG1 antibodies in the following categories: 1 patient with VRR was NF186 positive, and 2 patients were NF155 positive with DRG and mixed sensory-motor demyelinating neuropathy with optic neuritis, respectively.

Conclusion

The frequency of nodal–paranodal antibodies is similar among IMRN regardless of HIV status. Interpretation of the results in the context of HIV is challenging as there is uncertainty regarding pathogenicity of the antibodies, especially at low titres. Larger prospective immune studies are required to delineate pathogenicity in the context of HIV, and to establish a panel of antibodies to predict for a particular clinical phenotype.

背景:在患有慢性免疫介导的神经根性神经病(IMRN)的HIV感染患者中,结旁抗体的频率以前没有描述过。方法:对符合慢性IMRN纳入标准的HIV感染患者进行免疫球蛋白G(IgG)抗体筛选,该抗体针对淋巴结(神经筋膜素(NF)186)和副淋巴结(NF155,接触蛋白-1(CNTN1)和接触蛋白相关蛋白(Caspr1))细胞粘附分子,采用活细胞法。为了探索潜在的致病性,通过与淋巴结或副结抗体阳性的患者血清孵育来评估人IgG与有髓鞘共培养物的结合。添加正常人血清作为补体来源,以评估补体活化作为髓鞘损伤的机制。结果:24名HIV感染的IMRN患者被纳入研究,其中15名患有慢性炎症性脱髓鞘性多发性神经病(CIDP),4名患有腹根神经根病(VRR),5名患有背根神经节病(DRG)。5例CIDP患者合并中枢和外周脱髓鞘(CCPD)。以下类别中有3名患者(12.7%)的神经筋膜素IgG1抗体检测呈阳性:1名VRR患者为NF186阳性,2名DRG和混合感觉运动脱髓鞘神经病变伴视神经炎患者为NF155阳性。结论:无论HIV状况如何,IMRN中结旁抗体的频率相似。在HIV的背景下解释结果是具有挑战性的,因为抗体的致病性存在不确定性,尤其是在低滴度时。需要更大规模的前瞻性免疫研究来描述HIV的致病性,并建立一组抗体来预测特定的临床表型。
{"title":"Nodal–paranodal antibodies in HIV-immune mediated radiculo-neuropathies: Clinical phenotypes and relevance","authors":"K. Moodley,&nbsp;V. B. Patel,&nbsp;A. A. Moodley,&nbsp;P. L. A. Bill,&nbsp;A. Kajee,&nbsp;V. Mgbachi,&nbsp;J. Fehmi,&nbsp;S. Rinaldi","doi":"10.1111/jns.12596","DOIUrl":"10.1111/jns.12596","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The frequency of nodal–paranodal antibodies in HIV-infected patients with chronic immune-mediated radiculo-neuropathies (IMRN) has not been previously described.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>HIV-infected patients who met the inclusion criteria for chronic IMRN were screened for immunoglobulin G (IgG) antibodies directed against nodal (neurofascin (NF)186) and paranodal (NF155, contactin-1 (CNTN1) and contactin-associated protein(Caspr1)) cell adhesion molecules, using a live, cell-based assay.</p>\u0000 \u0000 <p>To explore potential pathogenicity, binding of human IgG to myelinated co-cultures was assessed by incubation with patients' sera positive for nodal or paranodal antibodies. Normal human serum was added as a source of complement to assess for complement activation as a mechanism for myelin injury.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twenty-four HIV-infected patients with IMRN were included in the study, 15 with chronic inflammatory demyelinating polyneuropathy (CIDP), 4 with ventral root radiculopathies (VRR), and 5 with dorsal root ganglionopathies (DRG). Five patients with CIDP had combined central and peripheral demyelination (CCPD). Three patients (12.7%) tested positive for neurofascin IgG1 antibodies in the following categories: 1 patient with VRR was NF186 positive, and 2 patients were NF155 positive with DRG and mixed sensory-motor demyelinating neuropathy with optic neuritis, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The frequency of nodal–paranodal antibodies is similar among IMRN regardless of HIV status. Interpretation of the results in the context of HIV is challenging as there is uncertainty regarding pathogenicity of the antibodies, especially at low titres. Larger prospective immune studies are required to delineate pathogenicity in the context of HIV, and to establish a panel of antibodies to predict for a particular clinical phenotype.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.12596","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10180465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Vestibular impairment in Guillain-Barré syndrome 格林-巴利综合征的前庭功能障碍
IF 3.8 3区 医学 Q1 Medicine Pub Date : 2023-09-04 DOI: 10.1111/jns.12593
Gülden Akdal, Koray Koçoğlu, Rahmi Tümay Ala, Tural Tanrıverdizade, Pınar Özçelik, İhsan Şükrü Şengün
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引用次数: 0
期刊
Journal of the Peripheral Nervous System
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