Journal of the Peripheral Nervous System最新文献

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.

{"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

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.

{"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

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.

{"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

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.

{"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

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。

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引用次数: 0

Ultrasound Shear Wave Velocity of Peripheral Nerves: A Possible Non-Invasive Biomarker for Demyelinating Neuropathies

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。

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引用次数: 0

Altered Cellular Pathways in the Blood of Patients With Guillain-Barre Syndrome

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.

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引用次数: 0

Feasibility and Reliability of a Monitoring App for Chronic Inflammatory Neuropathies

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.

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引用次数: 0

Paraneoplastic Leucine Zipper 4 IgG Associated Motor-Predominant Polyradiculoneuropathy

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.

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引用次数: 0

Loss of MEGF10 Decreases the Number of Perisynaptic Schwann Cells and Innervation of Neuromuscular Junctions in Aging Mice 缺失 MEGF10 会减少老龄小鼠突触周围许旺细胞的数量和神经肌肉接头的神经支配能力

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.70014

Devin Juros, Robert Louis Hastings, Ariane Pendragon, Jeremy Kay, Gregorio Valdez

Background and Aims

At the neuromuscular junction (NMJ), the synapse between motor neurons and muscle fibers, reside perisynaptic Schwann cells (PSCs) which are specialized glia that regulate the maintenance and repair of this synapse. While we know how PSC morphology and numbers change in aging and various neuromuscular disorders that adversely affect the NMJ, the molecular mechanisms that alter PSC functions remain unknown. In this study, we investigated whether MEGF10 in PSCs modulates NMJ stability in developing, healthy young adult, middle-aged, and axotomized mice. MEGF10 is a glial phagocytic receptor that is enriched in PSCs compared to other Schwann cells (SCs).

Methods

We isolated PSCs from a transgenic reporter mouse line to assess Megf10 expression at different ages and following nerve injury using qPCR. We then used a conditional mouse lacking Megf10 in all SCs, including PSCs (Megf10 SC-KO mice). We examined NMJs and axonal debris clearance in Megf10 SC-KO mice using confocal microscopy.

Results

We found that Megf10 expression in PSCs peaks during development and decreases during aging and following denervation of NMJs. NMJs were morphologically normal in developing and young adult Megf10 SC-KO mice. This was not the case in middle-aged Megf10 SC-KO mice, in which NMJs presented with fewer PSCs, decreased PSC coverage of the endplate, and decreased innervation in comparison to control mice. Following nerve injury-induced damage, axonal debris at the NMJ was cleared faster in Megf10 SC-KO mice; yet, the rate of reinnervation was unchanged compared to control mice.

Interpretation

The data in this study suggest that MEGF10 in PSCs functions to maintain PSC number and NMJ innervation during aging. This study also suggests important roles for MEGF10 in mediating the clearance of axonal debris at NMJs following nerve injury.

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引用次数: 0