Journal of the Peripheral Nervous System最新文献_第8页

Acquired Transthyretin Amyloidosis in Domino Liver Transplantation Treated With Gene-Silencers 基因沉默剂治疗骨牌肝移植后获得性转甲状腺蛋白淀粉样变性

IF 3.9 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Peripheral Nervous System

Pub Date : 2025-05-06 DOI: 10.1111/jns.70023

Alessandro Salvalaggio, Alberto Cipriani, Luisa Frizziero, Manuele Marasca, Mario Cacciavillani, Chiara Briani

引用次数: 0

New Approaches Based on Serial-Block Face Electron Microscopy to Investigate the Peripheral Nervous System 基于序列块面电子显微镜研究外周神经系统的新方法

IF 3.9 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Peripheral Nervous System

Pub Date : 2025-04-19 DOI: 10.1111/jns.70019

Vitalijs Borisovs, Mario Bossi, Laura Matino, Paola Marmiroli, Guido Cavaletti

Background and Aims

Serial block face scanning electron microscopy (SBF-SEM) enables automated 3D imaging of specimens with ultrastructural resolution. However, its application is often restricted due to the complex and labor-intensive nature of the processes involved. This study addresses the challenges associated with sample preparation and the final 3D reconstruction for ultrastructural analysis of peripheral nerves and dorsal root ganglia (DRG) specimens.

Methods

Specimens from the caudal nerve and DRG of mice were prepared for SBF-SEM using three different techniques: (1) manual high molecular weight staining, regarded as the gold standard, (2) automated standard transmission electron microscopy (TEM) preparation, and (3) automated uranyl-free en bloc preparation. The acquired data were processed by combining different software programs for image analysis and 3D rendering.

Results

Upon analyzing all samples, the high molecular weight method demonstrated its superiority. Nonetheless, the two alternative methods produced high-quality images of the caudal nerve. Consequently, 3D rendering was successfully achieved for all samples using an automated approach. The investigation of DRG specimens posed greater challenges with the standard TEM preparation due to the low contrast of smaller organelles compared to the cytosol, whereas the uranyl-free protocol provided significantly improved contrast.

Interpretation

Our findings indicate that automated uranyl-free staining can effectively compete with the traditional gold standard manual and uranyl-based staining methods, albeit with some limitations. Furthermore, high-quality SBF-SEM imaging is attainable, especially in peripheral nerves, using samples prepared via the standard TEM method, thereby facilitating the analysis of previously embedded samples even if they were not specifically prepared for 3D examination.

背景和目的连续块面扫描电子显微镜（SBF-SEM）能够实现具有超微结构分辨率的标本自动三维成像。然而，由于所涉及的过程的复杂性和劳动密集性，其应用往往受到限制。本研究解决了与周围神经和背根神经节（DRG）标本超微结构分析的样品制备和最终3D重建相关的挑战。方法采用三种不同的技术(1)人工高分子量染色作为金标准，(2)自动标准透射电子显微镜（TEM）制备，(3)自动无铀酰整体制备小鼠尾神经和DRG标本进行SBF-SEM制备。将采集到的数据结合不同的软件程序进行图像分析和三维绘制。结果通过对所有样品的分析，证明了高分子量法的优越性。尽管如此，这两种方法都能获得高质量的尾神经图像。因此，使用自动化方法成功实现了所有样本的3D渲染。由于与细胞质溶胶相比，较小的细胞器对比度较低，因此对DRG样品的研究在标准TEM制备中面临更大的挑战，而无铀酰方案可显着提高对比度。我们的研究结果表明，自动化无铀酰染色可以有效地与传统的金标准手工染色和基于铀酰的染色方法竞争，尽管存在一些局限性。此外，使用通过标准TEM方法制备的样品，可以获得高质量的SBF-SEM成像，特别是在周围神经中，从而有助于分析先前嵌入的样品，即使它们不是专门为3D检查准备的。

{"title":"New Approaches Based on Serial-Block Face Electron Microscopy to Investigate the Peripheral Nervous System","authors":"Vitalijs Borisovs, Mario Bossi, Laura Matino, Paola Marmiroli, Guido Cavaletti","doi":"10.1111/jns.70019","DOIUrl":"https://doi.org/10.1111/jns.70019","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Serial block face scanning electron microscopy (SBF-SEM) enables automated 3D imaging of specimens with ultrastructural resolution. However, its application is often restricted due to the complex and labor-intensive nature of the processes involved. This study addresses the challenges associated with sample preparation and the final 3D reconstruction for ultrastructural analysis of peripheral nerves and dorsal root ganglia (DRG) specimens.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Specimens from the caudal nerve and DRG of mice were prepared for SBF-SEM using three different techniques: (1) manual high molecular weight staining, regarded as the gold standard, (2) automated standard transmission electron microscopy (TEM) preparation, and (3) automated uranyl-free en bloc preparation. The acquired data were processed by combining different software programs for image analysis and 3D rendering.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Upon analyzing all samples, the high molecular weight method demonstrated its superiority. Nonetheless, the two alternative methods produced high-quality images of the caudal nerve. Consequently, 3D rendering was successfully achieved for all samples using an automated approach. The investigation of DRG specimens posed greater challenges with the standard TEM preparation due to the low contrast of smaller organelles compared to the cytosol, whereas the uranyl-free protocol provided significantly improved contrast.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Our findings indicate that automated uranyl-free staining can effectively compete with the traditional gold standard manual and uranyl-based staining methods, albeit with some limitations. Furthermore, high-quality SBF-SEM imaging is attainable, especially in peripheral nerves, using samples prepared via the standard TEM method, thereby facilitating the analysis of previously embedded samples even if they were not specifically prepared for 3D examination.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"30 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.70019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143849037","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

Genetic and Clinical Features of 10 Families With Hereditary Sensory Neuropathies 10个家族遗传性感觉神经病变的遗传和临床特征

IF 3.9 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Peripheral Nervous System

Pub Date : 2025-04-10 DOI: 10.1111/jns.70020

Ke Xu, Zhongzheng Li, Mengli Wang, Lei Liu, Sen Zeng, Xiaobo Li, Wanqian Cao, Shunxiang Huang, Huadong Zhao, Yan Yang, Yongzhi Xie, Zhengmao Hu, Beisha Tang, Ruxu Zhang

Background and Objectives

Hereditary sensory neuropathies (HSNs) are a group of genetically and clinically heterogeneous diseases. Our study aims to summarize the genetic and clinical features of HSNs in 10 Chinese families.

Methods

Clinical data from 10 families with HSNs were collected retrospectively. Genetic screening was performed by whole exome sequencing (WES). Repeated-primed PCR and capillary electrophoresis were performed for WES-negative patients to analyze repeat expansions in RFC1.

Results

Among the 10 probands with HSNs, eight cases were sporadic, and two had a positive family history. Six probands had early-onset (onset age < 20 years). Seven probands presented with pure-HSNs type, and three exhibited HSNs-complex type with ataxia. Variants in the NTRK1, SPTLC1, COX20, PUM1, and RFC1 genes were detected in six probands. A novel variant, c.444C>A (p.N148K), in NTRK1 was identified in an autosomal recessive inheritance family with HSAN-IV, and a novel variant, c.182dup (p.H61Qfs*31), in PUM1 was identified in a proband with adult-onset paresthesia and mild cerebellar ataxia. Additionally, biallelic expansion of the pathogenic variant structure (AAGGG)exp repeat amplification in the RFC1 gene was identified in a proband with sensory neuropathy, ataxia, and right vestibular hypofunction.

Conclusions

The novel variants in NTRK1 and PUM1 expanded the genotypic spectrum of HSNs. This study highlights the associations between sensory neuropathies and other symptoms, particularly cerebellar ataxia. Given the ultra-rarity of HSNs, future multicenter studies with larger cohorts may facilitate the identification of novel variants, improve genetic diagnostic rates, and enhance disease recognition.

背景和目的遗传性感觉神经病（hsn）是一组遗传和临床异质性疾病。我们的研究旨在总结10个中国家庭hsn的遗传和临床特征。方法回顾性收集10个HSNs家族的临床资料。采用全外显子组测序（WES）进行遗传筛选。对wes阴性患者进行重复引物PCR和毛细管电泳，分析RFC1重复扩增。结果10例先证者中8例为散发性，2例为阳性家族史。6个先证者早发（发病年龄20岁）。7个先证为纯hsn型，3个先证为hsn复合型伴共济失调。在6个先证者中检测到NTRK1、SPTLC1、COX20、PUM1和RFC1基因的变异。在HSAN-IV常染色体隐性遗传家族中发现了NTRK1的新变异c.444C>A (p.N148K)，在患有成人发病的感觉异常和轻度小脑性共济失调的先证患者中发现了PUM1的新变异c.182dup （p.H61Qfs*31）。此外，在一个感觉神经病变、共济失调和右侧前庭功能减退的先证者中发现了RFC1基因中致病性变异结构（AAGGG）双等位基因扩增exp重复扩增。结论NTRK1和PUM1的新变异扩大了hsn的基因型谱。这项研究强调了感觉神经病变和其他症状之间的联系，特别是小脑性共济失调。鉴于hsn的超罕见性，未来的多中心研究和更大的队列可能有助于识别新的变异，提高遗传诊断率，增强疾病识别。

{"title":"Genetic and Clinical Features of 10 Families With Hereditary Sensory Neuropathies","authors":"Ke Xu, Zhongzheng Li, Mengli Wang, Lei Liu, Sen Zeng, Xiaobo Li, Wanqian Cao, Shunxiang Huang, Huadong Zhao, Yan Yang, Yongzhi Xie, Zhengmao Hu, Beisha Tang, Ruxu Zhang","doi":"10.1111/jns.70020","DOIUrl":"https://doi.org/10.1111/jns.70020","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Objectives</h3>\u0000 \u0000 <p>Hereditary sensory neuropathies (HSNs) are a group of genetically and clinically heterogeneous diseases. Our study aims to summarize the genetic and clinical features of HSNs in 10 Chinese families.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Clinical data from 10 families with HSNs were collected retrospectively. Genetic screening was performed by whole exome sequencing (WES). Repeated-primed PCR and capillary electrophoresis were performed for WES-negative patients to analyze repeat expansions in <i>RFC1</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the 10 probands with HSNs, eight cases were sporadic, and two had a positive family history. Six probands had early-onset (onset age < 20 years). Seven probands presented with pure-HSNs type, and three exhibited HSNs-complex type with ataxia. Variants in the <i>NTRK1, SPTLC1, COX20, PUM1,</i> and <i>RFC1</i> genes were detected in six probands. A novel variant, c.444C>A (p.N148K), in <i>NTRK1</i> was identified in an autosomal recessive inheritance family with HSAN-IV, and a novel variant, c.182dup (p.H61Qfs*31), in <i>PUM1</i> was identified in a proband with adult-onset paresthesia and mild cerebellar ataxia. Additionally, biallelic expansion of the pathogenic variant structure (AAGGG)exp repeat amplification in the <i>RFC1</i> gene was identified in a proband with sensory neuropathy, ataxia, and right vestibular hypofunction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The novel variants in <i>NTRK1</i> and <i>PUM1</i> expanded the genotypic spectrum of HSNs. This study highlights the associations between sensory neuropathies and other symptoms, particularly cerebellar ataxia. Given the ultra-rarity of HSNs, future multicenter studies with larger cohorts may facilitate the identification of novel variants, improve genetic diagnostic rates, and enhance disease recognition.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"30 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143818391","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

Diagnosis and Management of Multifocal Motor Neuropathy in the United Kingdom: A Multicentre Survey 英国多局灶性运动神经病的诊断和治疗：一项多中心调查

IF 3.9 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Peripheral Nervous System

Pub Date : 2025-04-10 DOI: 10.1111/jns.70018

Yusuf A. Rajabally, Christina Englezou, Grace Cluett, Roberto Bellanti, Simon Rinaldi, Mow Wei Chin, Robert Hadden, Madalina Roman, Channa Hewamadduma, Ashleigh Murray, Amar Elsaddig, Tim Lavin, Oliver Cousins, Niranjanan Nirmalananthan, Joumana Freiha, Chinar Osman, Matthew Evans, Aisling Carr, James K. L. Holt

Background

We conducted a survey to determine the current diagnosis and treatment of multifocal motor neuropathy (MMN) in the United Kingdom.

Methods

Demographic, diagnostic and treatment data were collected at nine UK neuroscience centres.

Results

Ninety-five subjects were included. Mean age at diagnosis was 49.9 years (SD: 11.4). Males were more commonly affected (ratio: 1.9:1). Diagnostic delay was > 1 year from the time of first neurological assessment, in > 50% of subjects. Applying modified EFNS/PNS 2010 criteria, 69/95 (72.6%) had definite MMN, 10/95 (10.5%) had probable MMN, 15/95 (15.8%) had possible MMN, through treatment responsiveness in 9/15 (60%) and 1/95 (1.1%) did not meet criteria. Cerebrospinal fluid examination, anti-GM1 antibody testing and brachial plexus magnetic resonance imaging were non-contributory. Immunoglobulin response was reported in 90/92 subjects (97.8%), and 84/90 (93.3%) remained on treatment after a mean of 9.4 years, at a mean dose of 26.2 g/week (range: 4–114). Mean long-term immunoglobulin dose was 30%–60% higher than reported in neighbouring countries. Contrasting with previous reports of frequent loss of immunoglobulin response and functional decline, our physician-assessed long-term outcome was favourable (stable or improving) in 74/84 (88.1%) treated subjects.

Interpretation

MMN diagnosis and treatment in the United Kingdom are comparable to that of neighbouring countries and follow existing guidelines. Diagnostic delay after the first neurological assessment is considerable. Electrophysiology shows at least one definite/probable conduction block in nearly 90% of cases. The mean long-term immunoglobulin dose is higher in the United Kingdom than reported elsewhere, although highly variable. Whether higher doses of immunoglobulin may improve long-term outcomes requires further study.

我们进行了一项调查，以确定英国多灶性运动神经病变（MMN）的诊断和治疗现状。方法收集英国9个神经科学中心的人口学、诊断和治疗数据。结果纳入95名受试者。平均诊断年龄为49.9岁（SD: 11.4）。男性更常见（比例：1.9:1）。在50%的受试者中，诊断延迟为首次神经学评估后1年。应用修改后的EFNS/PNS 2010标准，69/95例（72.6%）有明确MMN， 10/95例（10.5%）有可能MMN， 15/95例（15.8%）有可能MMN， 9/15例（60%）和1/95例（1.1%）的治疗反应不符合标准。脑脊液检查，抗gm1抗体检测和臂丛磁共振成像无贡献。92例受试者中有90例（97.8%）出现免疫球蛋白应答，84例（93.3%）在平均9.4年后仍在接受治疗，平均剂量为26.2 g/周（范围：4-114）。平均长期免疫球蛋白剂量比邻国报告的高30%-60%。与先前报道的免疫球蛋白反应频繁丧失和功能下降相比，我们的医生评估的长期结果是有利的（稳定或改善）74/84（88.1%）接受治疗的受试者。英国MMN的诊断和治疗与邻国相当，并遵循现有指南。首次神经学评估后的诊断延迟是相当可观的。电生理学显示近90%的病例至少有一个明确/可能的传导阻滞。英国的平均长期免疫球蛋白剂量高于其他地方的报告，尽管差异很大。更高剂量的免疫球蛋白是否能改善长期疗效还需要进一步研究。

{"title":"Diagnosis and Management of Multifocal Motor Neuropathy in the United Kingdom: A Multicentre Survey","authors":"Yusuf A. Rajabally, Christina Englezou, Grace Cluett, Roberto Bellanti, Simon Rinaldi, Mow Wei Chin, Robert Hadden, Madalina Roman, Channa Hewamadduma, Ashleigh Murray, Amar Elsaddig, Tim Lavin, Oliver Cousins, Niranjanan Nirmalananthan, Joumana Freiha, Chinar Osman, Matthew Evans, Aisling Carr, James K. L. Holt","doi":"10.1111/jns.70018","DOIUrl":"https://doi.org/10.1111/jns.70018","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>We conducted a survey to determine the current diagnosis and treatment of multifocal motor neuropathy (MMN) in the United Kingdom.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Demographic, diagnostic and treatment data were collected at nine UK neuroscience centres.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Ninety-five subjects were included. Mean age at diagnosis was 49.9 years (SD: 11.4). Males were more commonly affected (ratio: 1.9:1). Diagnostic delay was > 1 year from the time of first neurological assessment, in > 50% of subjects. Applying modified EFNS/PNS 2010 criteria, 69/95 (72.6%) had definite MMN, 10/95 (10.5%) had probable MMN, 15/95 (15.8%) had possible MMN, through treatment responsiveness in 9/15 (60%) and 1/95 (1.1%) did not meet criteria. Cerebrospinal fluid examination, anti-GM1 antibody testing and brachial plexus magnetic resonance imaging were non-contributory. Immunoglobulin response was reported in 90/92 subjects (97.8%), and 84/90 (93.3%) remained on treatment after a mean of 9.4 years, at a mean dose of 26.2 g/week (range: 4–114). Mean long-term immunoglobulin dose was 30%–60% higher than reported in neighbouring countries. Contrasting with previous reports of frequent loss of immunoglobulin response and functional decline, our physician-assessed long-term outcome was favourable (stable or improving) in 74/84 (88.1%) treated subjects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>MMN diagnosis and treatment in the United Kingdom are comparable to that of neighbouring countries and follow existing guidelines. Diagnostic delay after the first neurological assessment is considerable. Electrophysiology shows at least one definite/probable conduction block in nearly 90% of cases. The mean long-term immunoglobulin dose is higher in the United Kingdom than reported elsewhere, although highly variable. Whether higher doses of immunoglobulin may improve long-term outcomes requires further study.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"30 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.70018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143818392","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

Neuropathy Progression in Acquired Amyloidosis After Domino Liver Transplantation 骨牌肝移植后获得性淀粉样变性的神经病变进展

IF 3.9 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Peripheral Nervous System

Pub Date : 2025-04-07 DOI: 10.1111/jns.70016

Catarina Falcão de Campos, Miguel Miranda, Isabel Castro, José Castro, Miguel Oliveira Santos, Isabel Conceição

Background and Aims

Domino liver transplantation (DLT) has been used to address the shortage of donor organs. However, recipients of liver grafts from patients with hereditary transthyretin amyloidosis (ATTRv) develop de novo transthyretin (TTR) amyloidosis. Our aim is to describe the clinical presentation of patients with acquired TTR amyloidosis and compare the rate of neuropathy progression (NP) with untreated ATTRv amyloidosis with neuropathy (ATTRv-NP) patients.

Methods

Patients with acquired TTR amyloidosis after DLT followed at a reference centre were evaluated. Medical records were reviewed for clinical characterization and systematic assessment of neuropathy. NP was defined as an increase in neuropathy impairment score of the lower limbs (NIS-LL) at 12 months and compared to a historical control group of untreated ATTRv amyloidosis patients.

Results

Twenty-four patients with acquired ATTR amyloidosis were included. Time from DLT to neuropathy onset was 9 $� � � \pm � � �$ 2.0 years and the majority of patients reported feet sensory changes as first symptom. Thirteen patients with ≥ 2 evaluations with 12-months interval were analysed. Almost all patients developed a neuropathic phenotype with small nerve fibre involvement. Neuropathy progression was similar to untreated ATTRv-NP patients.

Interpretation

Recipients from liver grafts of ATTRv patients develop de novo amyloidosis with clinical presentation and NP similar to untreated ATTRv amyloidosis patients. Study of these patients might help elucidate the pathways for ATTR fibril formation.

背景与目的多米诺骨牌肝移植（DLT）已被用于解决供体器官短缺的问题。然而，遗传性甲状腺转蛋白淀粉样变（ATTRv）患者的肝移植受体会发生新发甲状腺转蛋白淀粉样变（TTR）。我们的目的是描述获得性TTR淀粉样变患者的临床表现，并比较神经病变进展率（NP）与未经治疗的ATTRv淀粉样变伴神经病变（ATTRv-NP）患者。方法对DLT术后获得性TTR淀粉样变患者进行评价。临床特征和系统评估神经病变的医疗记录进行了审查。与未治疗的ATTRv淀粉样变患者的历史对照组相比，NP被定义为在12个月时下肢神经病变损害评分（NIS-LL）的增加。结果纳入24例获得性ATTR淀粉样变患者。从DLT到神经病发作的时间为9±$$ pm $$ 2.0年，大多数患者报告足部感觉改变为第一症状。对13例评价≥2次，间隔12个月的患者进行分析。几乎所有患者都表现为神经病变表型，累及小神经纤维。神经病变进展与未治疗的ATTRv-NP患者相似。解释肝移植后的ATTRv患者发生新发淀粉样变，其临床表现和NP与未治疗的ATTRv淀粉样变患者相似。对这些患者的研究可能有助于阐明ATTR纤维形成的途径。

{"title":"Neuropathy Progression in Acquired Amyloidosis After Domino Liver Transplantation","authors":"Catarina Falcão de Campos, Miguel Miranda, Isabel Castro, José Castro, Miguel Oliveira Santos, Isabel Conceição","doi":"10.1111/jns.70016","DOIUrl":"https://doi.org/10.1111/jns.70016","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Domino liver transplantation (DLT) has been used to address the shortage of donor organs. However, recipients of liver grafts from patients with hereditary transthyretin amyloidosis (ATTRv) develop de novo transthyretin (TTR) amyloidosis. Our aim is to describe the clinical presentation of patients with acquired TTR amyloidosis and compare the rate of neuropathy progression (NP) with untreated ATTRv amyloidosis with neuropathy (ATTRv-NP) patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients with acquired TTR amyloidosis after DLT followed at a reference centre were evaluated. Medical records were reviewed for clinical characterization and systematic assessment of neuropathy. NP was defined as an increase in neuropathy impairment score of the lower limbs (NIS-LL) at 12 months and compared to a historical control group of untreated ATTRv amyloidosis patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twenty-four patients with acquired ATTR amyloidosis were included. Time from DLT to neuropathy onset was 9 <span></span><math>\u0000 <semantics>\u0000 <mrow>\u0000 <mo>±</mo>\u0000 </mrow>\u0000 <annotation>$$ pm $$</annotation>\u0000 </semantics></math> 2.0 years and the majority of patients reported feet sensory changes as first symptom. Thirteen patients with ≥ 2 evaluations with 12-months interval were analysed. Almost all patients developed a neuropathic phenotype with small nerve fibre involvement. Neuropathy progression was similar to untreated ATTRv-NP patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Recipients from liver grafts of ATTRv patients develop de novo amyloidosis with clinical presentation and NP similar to untreated ATTRv amyloidosis patients. Study of these patients might help elucidate the pathways for ATTR fibril formation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"30 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143793606","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

CIDP Treatment Outcomes Correlation With First Nerve Conduction Changes: Ascertainment of Initial and Long-Term Responders CIDP治疗结果与第一神经传导改变的相关性：确定初始和长期应答者

IF 3.9 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Peripheral Nervous System

Pub Date : 2025-04-06 DOI: 10.1111/jns.70017

Thapat Wannarong, Michael P. Skolka, Natthapon Rattanathamsakul, Grace Swart, James B. Dyck, Sarah E. Berini, Divyanshu Dubey, Kamal Shouman, Marcus V. Pinto, Michelle L. Mauermann, Anthony J. Windebank, Nathan P. Staff, Christopher J. Klein

Background and Aims

Nerve conduction studies (NCS) are integral to diagnosing chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), but their role in predicting treatment outcomes remains underexplored. This study evaluates NCS changes at first follow-up (first NCS changes) as predictors of treatment success in CIDP, focusing on their correlation with clinical outcomes over time.

Methods

Newly diagnosed CIDP patients meeting the 2021 EAN/PNS criteria were retrospectively evaluated. Baseline and first follow-up NCS parameters were compared with clinical outcomes, assessed by the Neuropathy Impairment Score (NIS) and Inflammatory Neuropathy Cause and Treatment (INCAT) disability score. All patients received first-line immunotherapy (intravenous immunoglobulin, corticosteroids, or plasma exchange).

Results

Of 39 treated patients, 26 (66.7%) were responders based on improving NIS trends, while 13 (33.3%) were nonresponders. Responders showed significant improvements at the first follow-up in fibular compound muscle action potential (CMAP) amplitude, ulnar CMAP amplitude, summated CMAP amplitudes, and fibular motor conduction velocity. Changes in fibular CMAP amplitude consistently correlated with NIS (R = −0.8 to −0.6, p ≤ 0.004) and INCAT disability score improvements (R = −0.6 to −0.3, p ≤ 0.032) across all follow-up intervals up to 60 months. Ulnar and summated CMAP amplitude changes also correlated with clinical outcomes, though their associations were less sustained than those of fibular CMAP amplitude.

Interpretation

The first change in fibular CMAP amplitude is a reliable biomarker for predicting CIDP treatment response, with ulnar and summated CMAP amplitudes as alternatives when the fibular response is absent. Our findings highlight the utility of first NCS changes in monitoring and predicting treatment outcomes in CIDP.

背景和目的神经传导研究（NCS）是诊断慢性炎症性脱髓鞘多发性神经病（CIDP）不可或缺的一部分，但其在预测治疗效果方面的作用仍未得到充分探索。本研究将首次随访时的 NCS 变化（首次 NCS 变化）作为 CIDP 治疗成功的预测因素进行评估，重点关注其与长期临床结果的相关性。方法对符合 2021 年 EAN/PNS 标准的新诊断 CIDP 患者进行回顾性评估。通过神经病变损害评分（NIS）和炎症性神经病变病因与治疗（INCAT）残疾评分对基线和首次随访的 NCS 参数与临床结果进行了比较。所有患者均接受了一线免疫疗法（静脉注射免疫球蛋白、皮质类固醇或血浆置换）。结果在 39 名接受治疗的患者中，有 26 人（66.7%）根据 NIS 改善趋势确定为应答者，13 人（33.3%）为非应答者。首次随访时，应答者的腓骨复合肌动电位（CMAP）振幅、尺侧 CMAP 振幅、CMAP 振幅总和以及腓骨运动传导速度均有明显改善。在长达 60 个月的所有随访期间，腓骨 CMAP 振幅的变化与 NIS（R = -0.8 至 -0.6，p ≤ 0.004）和 INCAT 残疾评分的改善（R = -0.6 至 -0.3，p ≤ 0.032）始终相关。尺骨和CMAP振幅总和的变化也与临床结果相关，但其关联性不如腓骨CMAP振幅的关联性持久。解释：腓骨 CMAP 振幅的首次变化是预测 CIDP 治疗反应的可靠生物标志物，当腓骨没有反应时，尺骨和加和 CMAP 振幅可作为替代物。我们的研究结果凸显了首次 NCS 变化在监测和预测 CIDP 治疗效果方面的实用性。

{"title":"CIDP Treatment Outcomes Correlation With First Nerve Conduction Changes: Ascertainment of Initial and Long-Term Responders","authors":"Thapat Wannarong, Michael P. Skolka, Natthapon Rattanathamsakul, Grace Swart, James B. Dyck, Sarah E. Berini, Divyanshu Dubey, Kamal Shouman, Marcus V. Pinto, Michelle L. Mauermann, Anthony J. Windebank, Nathan P. Staff, Christopher J. Klein","doi":"10.1111/jns.70017","DOIUrl":"https://doi.org/10.1111/jns.70017","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Nerve conduction studies (NCS) are integral to diagnosing chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), but their role in predicting treatment outcomes remains underexplored. This study evaluates NCS changes at first follow-up (first NCS changes) as predictors of treatment success in CIDP, focusing on their correlation with clinical outcomes over time.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Newly diagnosed CIDP patients meeting the 2021 EAN/PNS criteria were retrospectively evaluated. Baseline and first follow-up NCS parameters were compared with clinical outcomes, assessed by the Neuropathy Impairment Score (NIS) and Inflammatory Neuropathy Cause and Treatment (INCAT) disability score. All patients received first-line immunotherapy (intravenous immunoglobulin, corticosteroids, or plasma exchange).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 39 treated patients, 26 (66.7%) were responders based on improving NIS trends, while 13 (33.3%) were nonresponders. Responders showed significant improvements at the first follow-up in fibular compound muscle action potential (CMAP) amplitude, ulnar CMAP amplitude, summated CMAP amplitudes, and fibular motor conduction velocity. Changes in fibular CMAP amplitude consistently correlated with NIS (<i>R</i> = −0.8 to −0.6, <i>p</i> ≤ 0.004) and INCAT disability score improvements (<i>R</i> = −0.6 to −0.3, <i>p</i> ≤ 0.032) across all follow-up intervals up to 60 months. Ulnar and summated CMAP amplitude changes also correlated with clinical outcomes, though their associations were less sustained than those of fibular CMAP amplitude.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>The first change in fibular CMAP amplitude is a reliable biomarker for predicting CIDP treatment response, with ulnar and summated CMAP amplitudes as alternatives when the fibular response is absent. Our findings highlight the utility of first NCS changes in monitoring and predicting treatment outcomes in CIDP.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"30 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143786813","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

Ultrasound Shear Wave Velocity of Peripheral Nerves: A Possible Non-Invasive Biomarker for Demyelinating Neuropathies 外周神经的超声剪切波速：脱髓鞘神经病变的一种可能的非侵入性生物标志物

IF 3.9 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Peripheral Nervous System

Pub Date : 2025-04-06 DOI: 10.1111/jns.70015

Ricardo J. Andrade, Antoine Nordez, Armelle Magot, Laura Couloume, Jean-Philippe Plançon, Jean-Baptiste Quillard, Robert S. Ware, Michel W. Coppieters, Yann Péréon, François Hug

Background and Aims

Repeated cycles of demyelination and remyelination alter nerve tissue composition, likely affecting its material properties, including stiffness. Using ultrasound shear wave elastography (SWE), we assessed nerve shear wave velocity (SWV), a surrogate measure of stiffness, to determine its potential as a biomarker for demyelinating neuropathies, including chronic inflammatory demyelinating polyneuropathy, Charcot-Marie-Tooth type 1A, and anti-myelin-associated glycoprotein neuropathy.

Methods

This cross-sectional study compared nerve SWV between 20 patients with demyelinating neuropathies (60.2 ± 13.1 years) and 16 age-matched controls (56.8 ± 10.8 years). Each participant underwent bilateral SWE of the proximal and distal segments of four peripheral nerves in the upper (median, ulnar and radial) and lower (sciatic-tibial) limbs. Measurements were conducted in different limb positions to mimic two nerve tensile states, yielding a total of 32 nerve stiffness measurements per participant. Conventional nerve cross-sectional area was further evaluated for each nerve and location.

Results

Individuals with demyelinating polyneuropathy exhibited increased nerve SWV compared to age-matched controls (mean difference = 0.7 m/s, 95%CI [0.5 to 0.9]; p < 0.0001). This difference was observed across all nerves and regions, with the largest difference noted in the tibial. Axial nerve tension amplified these differences. Additionally, moderate to high negative correlations were observed between motor nerve conduction and nerve SWV.

Interpretation

This study identifies significant neuropathy-associated alterations in peripheral nerve elasticity. Our findings suggest that nerve stiffness could be a promising biomarker for demyelinating neuropathies, and provide a basis for the development of standardized peripheral nerve SWE protocols.

背景和目的反复循环的脱髓鞘和再髓鞘化会改变神经组织的组成，从而可能影响其材料特性，包括硬度。我们使用超声剪切波弹性成像（SWE）评估了神经剪切波速度（SWV）--一种硬度的替代测量指标，以确定其作为脱髓鞘性神经病（包括慢性炎症性脱髓鞘性多发性神经病、1A型夏科-玛丽-牙神经病和抗髓鞘相关糖蛋白神经病）生物标志物的潜力。方法该横断面研究比较了 20 名脱髓鞘性神经病患者（60.2 ± 13.1 岁）和 16 名年龄匹配的对照组患者（56.8 ± 10.8 岁）的神经 SWV。每位受试者分别对上肢（正中神经、尺神经和桡神经）和下肢（坐骨神经-胫神经）的四条周围神经的近端和远端进行了双侧SWE测量。测量在不同的肢体位置进行，以模拟两种神经拉伸状态，每位参与者共进行了 32 次神经僵硬度测量。对每个神经和位置的常规神经横截面积进行了进一步评估。结果与年龄匹配的对照组相比，脱髓鞘性多发性神经病患者的神经 SWV 增加（平均差异 = 0.7 m/s，95%CI [0.5 至 0.9]；p < 0.0001）。所有神经和区域都存在这种差异，其中胫神经的差异最大。轴神经张力扩大了这些差异。此外，在运动神经传导和神经 SWV 之间观察到中度到高度的负相关。释义本研究确定了神经病变引起的周围神经弹性的显著改变。我们的研究结果表明，神经僵硬度可能是脱髓鞘神经病的一种有前途的生物标志物，并为制定标准化的外周神经 SWE 方案提供了依据。

{"title":"Ultrasound Shear Wave Velocity of Peripheral Nerves: A Possible Non-Invasive Biomarker for Demyelinating Neuropathies","authors":"Ricardo J. Andrade, Antoine Nordez, Armelle Magot, Laura Couloume, Jean-Philippe Plançon, Jean-Baptiste Quillard, Robert S. Ware, Michel W. Coppieters, Yann Péréon, François Hug","doi":"10.1111/jns.70015","DOIUrl":"https://doi.org/10.1111/jns.70015","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Repeated cycles of demyelination and remyelination alter nerve tissue composition, likely affecting its material properties, including stiffness. Using ultrasound shear wave elastography (SWE), we assessed nerve shear wave velocity (SWV), a surrogate measure of stiffness, to determine its potential as a biomarker for demyelinating neuropathies, including chronic inflammatory demyelinating polyneuropathy, Charcot-Marie-Tooth type 1A, and anti-myelin-associated glycoprotein neuropathy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This cross-sectional study compared nerve SWV between 20 patients with demyelinating neuropathies (60.2 ± 13.1 years) and 16 age-matched controls (56.8 ± 10.8 years). Each participant underwent bilateral SWE of the proximal and distal segments of four peripheral nerves in the upper (median, ulnar and radial) and lower (sciatic-tibial) limbs. Measurements were conducted in different limb positions to mimic two nerve tensile states, yielding a total of 32 nerve stiffness measurements per participant. Conventional nerve cross-sectional area was further evaluated for each nerve and location.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Individuals with demyelinating polyneuropathy exhibited increased nerve SWV compared to age-matched controls (mean difference = 0.7 m/s, 95%CI [0.5 to 0.9]; <i>p</i> < 0.0001). This difference was observed across all nerves and regions, with the largest difference noted in the tibial. Axial nerve tension amplified these differences. Additionally, moderate to high negative correlations were observed between motor nerve conduction and nerve SWV.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>This study identifies significant neuropathy-associated alterations in peripheral nerve elasticity. Our findings suggest that nerve stiffness could be a promising biomarker for demyelinating neuropathies, and provide a basis for the development of standardized peripheral nerve SWE protocols.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"30 2","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143786815","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

Altered Cellular Pathways in the Blood of Patients With Guillain-Barre Syndrome 格林-巴利综合征患者血液中细胞通路的改变

IF 3.9 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Peripheral Nervous System

Pub Date : 2025-03-18 DOI: 10.1111/jns.70012

Marília Fabiana de Oliveira Lima, Viviane Brito Nogueira, Wendy Maury, Mary Edythe Wilson, Mário Emílio Teixeira Dourado Júnior, Diego Gomes Teixeira, Selma Maria Bezerra Jeronimo

Background and Aims

Guillain-Barré syndrome (GBS) is a rare disorder, with a global incidence ranging from 1 to 2 individuals per 100,000 people/year. Infections and vaccines have been implicated as causes triggering GBS. The aim of the study was to identify host genes involved in the pathogenesis of GBS when Zika (ZIKV) and Chikungunya viruses (CHIKV) were introduced in Brazil.

Methods

A case–control study of GBS was performed when ZIKV and CHIKV were introduced into a naïve population. GBS was studied during both acute and postacute phases. RNA sequencing was conducted using whole blood.

Results

GBS typically manifested a week after rash and fever; acute inflammatory demyelinating polyradiculoneuropathy was more frequent. None of the GBS cases had a poor outcome. Serological assays for ZIKV and CHIKV revealed high titers of immunoglobulin G for both viruses in 9 out of 11 subjects. Metatranscriptomic analyses unveiled an increased abundance of reads attributed to Pseudomonas tolaasii and Toxoplasma gondii in the acute phase. Analysis of differentially expressed host genes during the acute phase revealed altered expression of genes associated with axogenesis, synapse assembly, and presynapse organization. Moreover, genes upregulated during acute GBS were primarily related to inflammation and the inflammasome pathways, including AIM2, NLR family genes and LRR-protein genes, and IL-10.

Interpretation

These findings suggest that inflammasome activation via AIM2 could play a role in tissue damage during GBS. Further investigation into the general activation of innate inflammatory responses is warranted to elucidate their potential contribution to the pathology of GBS.

背景和目的吉兰-巴勒综合征（GBS）是一种罕见的疾病，全球发病率为每10万人/年1至2例。感染和疫苗被认为是引发GBS的原因。该研究的目的是鉴定当寨卡病毒（ZIKV）和基孔肯雅病毒（CHIKV）传入巴西时参与GBS发病机制的宿主基因。方法将寨卡病毒和齐卡病毒分别引入naïve人群，进行GBS病例对照研究。在急性期和急性期后对GBS进行研究。采用全血进行RNA测序。结果GBS典型表现为皮疹和发热后1周；急性炎性脱髓鞘性多根神经病变更为常见。所有GBS病例均无不良预后。寨卡病毒和奇卡病毒的血清学检测显示，11名受试者中有9人对这两种病毒的免疫球蛋白G滴度都很高。超转录组学分析揭示了急性期由陶氏假单胞菌和刚地弓形虫引起的reads丰度增加。对急性期宿主基因差异表达的分析显示，与轴生、突触组装和突触前组织相关的基因表达发生了改变。此外，急性GBS期间上调的基因主要与炎症和炎性体通路相关，包括AIM2、NLR家族基因和lrr蛋白基因以及IL-10。这些发现表明，通过AIM2激活炎性小体可能在GBS期间的组织损伤中发挥作用。对先天炎症反应的一般激活的进一步研究是有必要的，以阐明它们对GBS病理的潜在贡献。

{"title":"Altered Cellular Pathways in the Blood of Patients With Guillain-Barre Syndrome","authors":"Marília Fabiana de Oliveira Lima, Viviane Brito Nogueira, Wendy Maury, Mary Edythe Wilson, Mário Emílio Teixeira Dourado Júnior, Diego Gomes Teixeira, Selma Maria Bezerra Jeronimo","doi":"10.1111/jns.70012","DOIUrl":"https://doi.org/10.1111/jns.70012","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Guillain-Barré syndrome (GBS) is a rare disorder, with a global incidence ranging from 1 to 2 individuals per 100,000 people/year. Infections and vaccines have been implicated as causes triggering GBS. The aim of the study was to identify host genes involved in the pathogenesis of GBS when Zika (ZIKV) and Chikungunya viruses (CHIKV) were introduced in Brazil.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A case–control study of GBS was performed when ZIKV and CHIKV were introduced into a naïve population. GBS was studied during both acute and postacute phases. RNA sequencing was conducted using whole blood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>GBS typically manifested a week after rash and fever; acute inflammatory demyelinating polyradiculoneuropathy was more frequent. None of the GBS cases had a poor outcome. Serological assays for ZIKV and CHIKV revealed high titers of immunoglobulin G for both viruses in 9 out of 11 subjects. Metatranscriptomic analyses unveiled an increased abundance of reads attributed to <i>Pseudomonas tolaasii</i> and <i>Toxoplasma gondii</i> in the acute phase. Analysis of differentially expressed host genes during the acute phase revealed altered expression of genes associated with axogenesis, synapse assembly, and presynapse organization. Moreover, genes upregulated during acute GBS were primarily related to inflammation and the inflammasome pathways, including AIM2, NLR family genes and LRR-protein genes, and IL-10.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>These findings suggest that inflammasome activation via AIM2 could play a role in tissue damage during GBS. Further investigation into the general activation of innate inflammatory responses is warranted to elucidate their potential contribution to the pathology of GBS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"30 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638835","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

Feasibility and Reliability of a Monitoring App for Chronic Inflammatory Neuropathies 慢性炎症性神经病监测应用程序的可行性和可靠性

IF 3.9 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Peripheral Nervous System

Pub Date : 2025-03-18 DOI: 10.1111/jns.70005

Doreen L. Lemmen, Ruben P. A. van Eijk, Jordi W. J. van Unnik, Jeffrey A. Allen, Yusuf A. Rajabally, Leonard H. van den Berg, W. Ludo van der Pol, H. Stephan Goedee

Background and Aims

Multifocal motor neuropathy (MMN) and chronic inflammatory demyelinating polyneuropathy (CIDP) are immune-mediated neuropathies characterized by muscle weakness and/or sensory deficits. Identifying treatment response, relapse, and stability can be challenging in these chronic, sometimes unpredictable, conditions. This study explores the potential of a monitoring app designed to address these challenges.

Methods

Patients were monitored weekly or monthly, based on stability and patient preference, using grip strength, modified timed-up-and go (mTUG), and patient-reported outcome measures (PROMs). User experience was evaluated via a questionnaire addressing content and ease of use (scale 0–10). Adherence was measured as the percentage of completed mandatory assessments. We investigated reliability using intra-class correlation coefficients (ICCs) and standard errors of the mean (SEM) of repeated measurements. Longitudinal changes were analyzed using linear mixed-effects models.

Results

We included 38 patients, with a mean follow-up of 11 months (IQR 4.6–19.5). The mean user experience score was 8.35/10 (range 7–10). Adherence was 93% (95% CI: 91.9%–94.1%). Reported remote measurements for grip strength were 1358/1468 (93%), and 1343/1430 (94%) for mTUG. Grip strength and mTUG ICCs were both 0.96 (95% CI: 0.93–0.98 and 0.92–0.99, respectively). The average SEM was 8.46% (95% CI: 6.58–10.28) for grip strength and 8.18% (95% CI: 6.12–10.41) for mTUG. Only grip strength changed significantly, increasing by 3.1 pounds per 6 months (95% CI: 0.61–5.83; p = 0.016).

Interpretation

Our study demonstrates that tele-neuromonitoring is feasible and reliable, showing high adherence, positive user experience and high ICCs. We anticipate tele-neuromonitoring could complement routine follow-up, enabling clinicians to make better-informed treatment decisions.

背景和目的多灶性运动神经病（MMN）和慢性炎症性脱髓鞘多神经病变（CIDP）是一种以肌肉无力和/或感觉缺陷为特征的免疫介导的神经病变。在这些慢性、有时不可预测的疾病中，确定治疗反应、复发和稳定性是具有挑战性的。本研究探讨了一款监测应用程序的潜力，该应用程序旨在应对这些挑战。方法根据稳定性和患者偏好，每周或每月对患者进行监测，使用握力，改良的定时-出发（mTUG）和患者报告的结果测量（PROMs）。用户体验通过一份针对内容和易用性的问卷进行评估（评分0-10）。依从性以完成强制性评估的百分比来衡量。我们使用类内相关系数（ICCs）和重复测量的平均标准误差（SEM）来调查可靠性。纵向变化分析采用线性混合效应模型。结果38例患者，平均随访11个月（IQR 4.6 ~ 19.5）。平均用户体验得分为8.35/10（范围7-10）。依从性为93% （95% CI: 91.9%-94.1%）。据报道mTUG的握力远程测量值分别为1358/1468（93%）和1343/1430（94%）。握力和mTUG icc均为0.96 （95% CI分别为0.93-0.98和0.92-0.99）。握力的平均SEM为8.46% (95% CI: 6.58-10.28)， mTUG的平均SEM为8.18% （95% CI: 6.12-10.41）。只有握力发生了显著变化，每6个月增加3.1磅(95% CI: 0.61-5.83；p = 0.016)。我们的研究表明，远程神经监测是可行和可靠的，具有高依从性，积极的用户体验和高icc。我们期望远程神经监测可以补充常规随访，使临床医生做出更明智的治疗决定。

{"title":"Feasibility and Reliability of a Monitoring App for Chronic Inflammatory Neuropathies","authors":"Doreen L. Lemmen, Ruben P. A. van Eijk, Jordi W. J. van Unnik, Jeffrey A. Allen, Yusuf A. Rajabally, Leonard H. van den Berg, W. Ludo van der Pol, H. Stephan Goedee","doi":"10.1111/jns.70005","DOIUrl":"https://doi.org/10.1111/jns.70005","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Multifocal motor neuropathy (MMN) and chronic inflammatory demyelinating polyneuropathy (CIDP) are immune-mediated neuropathies characterized by muscle weakness and/or sensory deficits. Identifying treatment response, relapse, and stability can be challenging in these chronic, sometimes unpredictable, conditions. This study explores the potential of a monitoring app designed to address these challenges.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients were monitored weekly or monthly, based on stability and patient preference, using grip strength, modified timed-up-and go (mTUG), and patient-reported outcome measures (PROMs). User experience was evaluated via a questionnaire addressing content and ease of use (scale 0–10). Adherence was measured as the percentage of completed mandatory assessments. We investigated reliability using intra-class correlation coefficients (ICCs) and standard errors of the mean (SEM) of repeated measurements. Longitudinal changes were analyzed using linear mixed-effects models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We included 38 patients, with a mean follow-up of 11 months (IQR 4.6–19.5). The mean user experience score was 8.35/10 (range 7–10). Adherence was 93% (95% CI: 91.9%–94.1%). Reported remote measurements for grip strength were 1358/1468 (93%), and 1343/1430 (94%) for mTUG. Grip strength and mTUG ICCs were both 0.96 (95% CI: 0.93–0.98 and 0.92–0.99, respectively). The average SEM was 8.46% (95% CI: 6.58–10.28) for grip strength and 8.18% (95% CI: 6.12–10.41) for mTUG. Only grip strength changed significantly, increasing by 3.1 pounds per 6 months (95% CI: 0.61–5.83; <i>p</i> = 0.016).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Our study demonstrates that tele-neuromonitoring is feasible and reliable, showing high adherence, positive user experience and high ICCs. We anticipate tele-neuromonitoring could complement routine follow-up, enabling clinicians to make better-informed treatment decisions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"30 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.70005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638767","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

Paraneoplastic Leucine Zipper 4 IgG Associated Motor-Predominant Polyradiculoneuropathy 副肿瘤亮氨酸拉链4 IgG相关运动显性多根神经病变

IF 3.9 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Peripheral Nervous System

Pub Date : 2025-03-18 DOI: 10.1111/jns.70013

Alex Panrudkevich, Duaa Jabari, Brendan Putko, Catherine Daley, Richard A. Lewis, Divyanshu Dubey, Marcus V. Pinto

Background and Aims

Leucine Zipper 4 (LUZP4)-immunoglobulin G (IgG) is a novel antibody implicated in germ cell tumor-related paraneoplastic neurologic syndrome. We report a case of painful, progressive tetraparesis associated with testicular seminoma and LUZP4-IgG seropositivity.

Case Report

A 51-year-old male presented with a 5-week history of lower limb predominant progressive weakness. Nerve conduction studies (NCS) and electromyography (EMG) revealed a subacute axonal polyradiculoneuropathy. MRI lumbar spine showed thickening of the cauda equina and enhancement of the lower thoracic spinal cord/conus. Cerebrospinal fluid (CSF) showed a lymphocytic pleocytosis, three oligoclonal bands, and mildly elevated protein. Initial treatment with intravenous immunoglobulin (IVIG) and prednisone produced temporary improvement. CT targeted retroperitoneal lymph node biopsy revealed a seminoma, which was treated with orchiectomy and chemotherapy. The testicular tissue was consistent with a regressed germ cell tumor. His course was subsequently refractory to IVIG, prednisone, and plasma exchange. LUZP4 antibodies were detected in serum, prompting treatment with cyclophosphamide and prednisone. At the 4-month follow-up, the patient had significant improvement in hand strength and had transitioned from walker to cane.

Interpretation

LUZP4-IgG seropositivity and identification of retroperitoneal seminoma confirmed a paraneoplastic neurologic syndrome, which is a CD8+ T-cell-mediated disorder. Aggressive immunotherapy was initiated, resulting in clinical improvement. This case underscores the importance of identifying specific serologic biomarkers that can inform therapeutic decisions and improve outcomes.

背景与目的Leucine Zipper 4 (LUZP4)-免疫球蛋白G （IgG）是一种与生殖细胞肿瘤相关的副肿瘤神经系统综合征有关的新型抗体。我们报告一例疼痛，进行性全萎与睾丸精原细胞瘤和LUZP4-IgG血清阳性。病例报告一名51岁男性，以5周下肢进行性无力为主。神经传导研究（NCS）和肌电图（EMG）显示亚急性轴突多神经根神经病。腰椎MRI显示马尾增厚，胸椎下段脊髓/圆锥增强。脑脊液显示淋巴细胞增多，三个寡克隆带，轻度蛋白升高。最初静脉注射免疫球蛋白（IVIG）和强的松治疗产生了暂时的改善。CT靶向腹膜后淋巴结活检显示精原细胞瘤，并接受睾丸切除术和化疗。睾丸组织符合退行性生殖细胞瘤。随后对IVIG、强的松和血浆置换治疗难治。血清中检出LUZP4抗体，提示给予环磷酰胺和强的松治疗。在4个月的随访中，患者的手部力量有了明显的改善，并且已经从助行器过渡到手杖。LUZP4-IgG血清阳性和腹膜后精原细胞瘤的鉴定证实了一种副肿瘤神经系统综合征，这是一种CD8+ t细胞介导的疾病。积极的免疫治疗开始，导致临床改善。该病例强调了确定特定血清学生物标志物的重要性，这些标志物可以为治疗决策提供信息并改善结果。

{"title":"Paraneoplastic Leucine Zipper 4 IgG Associated Motor-Predominant Polyradiculoneuropathy","authors":"Alex Panrudkevich, Duaa Jabari, Brendan Putko, Catherine Daley, Richard A. Lewis, Divyanshu Dubey, Marcus V. Pinto","doi":"10.1111/jns.70013","DOIUrl":"https://doi.org/10.1111/jns.70013","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Leucine Zipper 4 (LUZP4)-immunoglobulin G (IgG) is a novel antibody implicated in germ cell tumor-related paraneoplastic neurologic syndrome. We report a case of painful, progressive tetraparesis associated with testicular seminoma and LUZP4-IgG seropositivity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case Report</h3>\u0000 \u0000 <p>A 51-year-old male presented with a 5-week history of lower limb predominant progressive weakness. Nerve conduction studies (NCS) and electromyography (EMG) revealed a subacute axonal polyradiculoneuropathy. MRI lumbar spine showed thickening of the cauda equina and enhancement of the lower thoracic spinal cord/conus. Cerebrospinal fluid (CSF) showed a lymphocytic pleocytosis, three oligoclonal bands, and mildly elevated protein. Initial treatment with intravenous immunoglobulin (IVIG) and prednisone produced temporary improvement. CT targeted retroperitoneal lymph node biopsy revealed a seminoma, which was treated with orchiectomy and chemotherapy. The testicular tissue was consistent with a regressed germ cell tumor. His course was subsequently refractory to IVIG, prednisone, and plasma exchange. LUZP4 antibodies were detected in serum, prompting treatment with cyclophosphamide and prednisone. At the 4-month follow-up, the patient had significant improvement in hand strength and had transitioned from walker to cane.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>LUZP4-IgG seropositivity and identification of retroperitoneal seminoma confirmed a paraneoplastic neurologic syndrome, which is a CD8+ T-cell-mediated disorder. Aggressive immunotherapy was initiated, resulting in clinical improvement. This case underscores the importance of identifying specific serologic biomarkers that can inform therapeutic decisions and improve outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"30 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638769","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