首页 > 最新文献

Journal of the Peripheral Nervous System最新文献

英文 中文
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 CLINICAL NEUROLOGY 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。
{"title":"Mutational screening of Greek patients with axonal Charcot-Marie-Tooth disease using targeted next-generation sequencing: Clinical and molecular spectrum delineation","authors":"Zoi Kontogeorgiou,&nbsp;Chrisoula Kartanou,&nbsp;Michail Rentzos,&nbsp;Panagiotis Kokotis,&nbsp;Evangelos Anagnostou,&nbsp;Thomas Zambelis,&nbsp;Elisabeth Chroni,&nbsp;Argyris Dinopoulos,&nbsp;Marios Panas,&nbsp;Georgios Koutsis,&nbsp;Georgia Karadima","doi":"10.1111/jns.12598","DOIUrl":"10.1111/jns.12598","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Sixty index patients with CMT2, dHMN or HSN were screened by a combination of Sanger sequencing (<i>GJB1</i>) and next-generation sequencing custom-made gene panel covering 24 commonly mutated genes in axonal CMT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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 <i>GJB1</i> (11.7%), <i>MPZ</i> (5%) and <i>MFN2</i> (5%), followed by <i>DNM2</i> (3.3%) and <i>LRSAM1</i> (3.3%). Single cases were identified with mutations in <i>BSCL2</i>, <i>HSPB1</i> and <i>GDAP1</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"28 4","pages":"642-650"},"PeriodicalIF":3.8,"publicationDate":"2023-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.12598","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41132239","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
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 CLINICAL NEUROLOGY 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":"28 4","pages":"629-641"},"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 CLINICAL NEUROLOGY 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":"28 4","pages":"564-577"},"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 CLINICAL NEUROLOGY 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":"28 4","pages":"578-585"},"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 CLINICAL NEUROLOGY Pub Date : 2023-09-04 DOI: 10.1111/jns.12593
Gülden Akdal, Koray Koçoğlu, Rahmi Tümay Ala, Tural Tanrıverdizade, Pınar Özçelik, İhsan Şükrü Şengün
{"title":"Vestibular impairment in Guillain-Barré syndrome","authors":"Gülden Akdal,&nbsp;Koray Koçoğlu,&nbsp;Rahmi Tümay Ala,&nbsp;Tural Tanrıverdizade,&nbsp;Pınar Özçelik,&nbsp;İhsan Şükrü Şengün","doi":"10.1111/jns.12593","DOIUrl":"10.1111/jns.12593","url":null,"abstract":"","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"28 4","pages":"677-678"},"PeriodicalIF":3.8,"publicationDate":"2023-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10137303","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
Imbalance and lower limb tremor in chronic inflammatory demyelinating polyradiculoneuropathy: Reply to Letter to the Editor 慢性炎症性脱髓鞘多发性神经病的失衡和下肢震颤:回复致编辑的信
IF 3.8 3区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2023-09-04 DOI: 10.1111/jns.12592
Matthew Silsby, Steve Vucic
{"title":"Imbalance and lower limb tremor in chronic inflammatory demyelinating polyradiculoneuropathy: Reply to Letter to the Editor","authors":"Matthew Silsby,&nbsp;Steve Vucic","doi":"10.1111/jns.12592","DOIUrl":"10.1111/jns.12592","url":null,"abstract":"","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"28 4","pages":"679-680"},"PeriodicalIF":3.8,"publicationDate":"2023-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10500268","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: 2
Corneal confocal microscopy in small and mixed fiber neuropathy—Comparison with skin biopsy and cold detection in a large prospective cohort 小纤维和混合纤维神经病的角膜共焦显微镜与大型前瞻性队列中的皮肤活检和冷检测的比较。
IF 3.8 3区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2023-08-31 DOI: 10.1111/jns.12595
Asger Bjørnkær, Laura M. Gaist, Jakob V. Holbech, David Gaist, Martin Wirenfeldt, Søren H. Sindrup, Thomas Krøigård

Background and Aims

The diagnosis of small fiber neuropathy (SFN) is supported by reduced intraepidermal nerve fiber density (IENFD). The noninvasive method corneal confocal microscopy (CCM) has the potential to be a practical alternative. We aimed to estimate the diagnostic accuracy of CCM compared with IENFD and cold detection thresholds (CDT) in SFN and mixed fiber neuropathy (MFN).

Methods

CCM was performed in an unselected prospective cohort of patients with a clinical suspicion of polyneuropathy. Predefined criteria were used to classify SFN and MFN. Neuropathy scores, including the Utah early neuropathy scale (UENS), were used to describe severity. Patients with established other diagnoses were used for diagnostic specificity calculations.

Results

Data were taken from 680 patients, of which 244 had SFN or MFN. There was no significant difference in sensitivities [95%CI] of CCM (0.44 [0.38–0.51]), IEFND (0.43 [0.36–0.49]), and CDT (0.34 [0.29–0.41]). CCM specificity (0.75 [0.69–0.81]) was lower (p = .044) than for IENFD (0.99 [0.96–1.00]) but not than for CDT (0.81 [0.75–0.86]). The AUCs of the ROC curves of 0.63, 0.63 and 0.74 respectively, was lower for corneal nerve fiber density (p = .0012) and corneal nerve fiber length (p = .0015) compared with IENFD. While UENS correlated significantly with IENFD (p = .0016; R2 = .041) and CDT (p = .0002; R2 = .056), it did not correlate with CCM measures.

Interpretation

The diagnostic utility of CCM in SNF and MFN is limited by the low specificity compared with skin biopsy. Further, CCM is less suitable than skin biopsy and CDT as a marker for neuropathy severity.

背景和目的:表皮内神经纤维密度降低(IENFD)支持小纤维神经病(SFN)的诊断。非侵入性角膜共聚焦显微镜(CCM)有可能成为一种实用的替代方法。我们旨在评估CCM与IENFD和冷检测阈值(CDT)相比对SFN和混合纤维神经病(MFN)的诊断准确性。方法:在临床怀疑为多发性神经病的未经选择的前瞻性队列中进行CCM。使用预定义的标准对SFN和MFN进行分类。神经病变评分,包括犹他州早期神经病变量表(UENS),用于描述严重程度。已确定其他诊断的患者用于诊断特异性计算。结果:数据取自680名患者,其中244名患者患有SFN或MFN。CCM(0.44[0.38-0.51])、IEFND(0.43[0.36-0.49])和CDT(0.34[0.29-0.41])的敏感性[95%CI]没有显著差异。CCM特异性(0.75[0.69-0.81])较低(p = .044),而不是CDT(0.81[0.75-0.86])。ROC曲线的AUC分别为0.63、0.63和0.74,角膜神经纤维密度的AUC较低(p = .0012)和角膜神经纤维长度(p = .0015)与IENFD相比。UENS与IENFD显著相关(p = .0016;R2 = .041)和CDT(p = .0002;R2 = .056),它与CCM测量没有相关性。解释:CCM在SNF和MFN中的诊断作用受到与皮肤活检相比特异性低的限制。此外,CCM不如皮肤活检和CDT适合作为神经病变严重程度的标志物。
{"title":"Corneal confocal microscopy in small and mixed fiber neuropathy—Comparison with skin biopsy and cold detection in a large prospective cohort","authors":"Asger Bjørnkær,&nbsp;Laura M. Gaist,&nbsp;Jakob V. Holbech,&nbsp;David Gaist,&nbsp;Martin Wirenfeldt,&nbsp;Søren H. Sindrup,&nbsp;Thomas Krøigård","doi":"10.1111/jns.12595","DOIUrl":"10.1111/jns.12595","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>The diagnosis of small fiber neuropathy (SFN) is supported by reduced intraepidermal nerve fiber density (IENFD). The noninvasive method corneal confocal microscopy (CCM) has the potential to be a practical alternative. We aimed to estimate the diagnostic accuracy of CCM compared with IENFD and cold detection thresholds (CDT) in SFN and mixed fiber neuropathy (MFN).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>CCM was performed in an unselected prospective cohort of patients with a clinical suspicion of polyneuropathy. Predefined criteria were used to classify SFN and MFN. Neuropathy scores, including the Utah early neuropathy scale (UENS), were used to describe severity. Patients with established other diagnoses were used for diagnostic specificity calculations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Data were taken from 680 patients, of which 244 had SFN or MFN. There was no significant difference in sensitivities [95%CI] of CCM (0.44 [0.38–0.51]), IEFND (0.43 [0.36–0.49]), and CDT (0.34 [0.29–0.41]). CCM specificity (0.75 [0.69–0.81]) was lower (<i>p</i> = .044) than for IENFD (0.99 [0.96–1.00]) but not than for CDT (0.81 [0.75–0.86]). The AUCs of the ROC curves of 0.63, 0.63 and 0.74 respectively, was lower for corneal nerve fiber density (<i>p</i> = .0012) and corneal nerve fiber length (<i>p</i> = .0015) compared with IENFD. While UENS correlated significantly with IENFD (<i>p</i> = .0016; <i>R</i><sup>2</sup> = .041) and CDT (<i>p</i> = .0002; <i>R</i><sup>2</sup> = .056), it did not correlate with CCM measures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>The diagnostic utility of CCM in SNF and MFN is limited by the low specificity compared with skin biopsy. Further, CCM is less suitable than skin biopsy and CDT as a marker for neuropathy severity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"28 4","pages":"664-676"},"PeriodicalIF":3.8,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.12595","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10119871","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
Expanding the genetic and clinical spectrum of SORD-related peripheral neuropathy by reporting a novel variant c.210T>G and evidence of subclinical muscle involvement 通过报告一种新型变体 c.210T>G 和亚临床肌肉受累的证据,扩展了 SORD 相关周围神经病变的遗传和临床范围
IF 3.8 3区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2023-08-16 DOI: 10.1111/jns.12591
Lu Li, Yongzhi Xie, Sen Zeng, Xiaobo Li, Zhiqiang Lin, Shunxiang Huang, Huadong Zhao, Wanqian Cao, Lei Liu, Jun Liu, Pengfei Rong, Ruxu Zhang

Background and Aims

Biallelic variants in the sorbitol dehydrogenase (SORD) gene have been identified as the genetic cause of autosomal recessive (AR) peripheral neuropathy (PN) manifesting as Charcot–Marie–Tooth disease type 2 (CMT2) or distal hereditary motor neuropathy (dHMN). We aim to observe the genetic and clinical spectrum of a cohort of patients with SORD-related PN (SORD-PN).

Methods

A total of 107 patients with AR or sporadic CMT2/dHMN underwent molecular diagnosis by whole-exome sequencing and subsequent Sanger sequencing validation. Available phenotypic data for SORD-PN were collected and analyzed.

Results

Eleven (10.28%) of 107 patients were identified as SORD-PN, including four with CMT2 and seven with dHMN. The SORD variant c.210 T > G;p.His70Gln in F-d3 was firstly reported and subsequent analysis showed that it resulted in loss of SORD enzyme function. Evidence of subclinical muscle involvement was frequently detected in patients with SORD-PN, including mildly to moderately elevated serum creatine kinase (CK) levels in 10 patients, myogenic electrophysiological changes in one patient, and muscle edema in five patients undergoing lower extremity MRI. Fasting serum sorbitol level was 88-fold higher in SORD-PN patients (9.69 ± 1.07 mg/L) than in healthy heterozygous subjects (0.11 ± 0.01 mg/L) and 138-fold higher than in healthy controls (0.07 ± 0.02 mg/L).

Interpretation

The novel SORD variant c.210 T > G;p.His70Gln and evidence of subclinical muscle involvement were identified, which expanded the genetic and clinical spectrum of SORD-PN. Subclinical muscle involvement might be a common but easily overlooked clinical feature. The serum CK and fasting serum sorbitol levels were expected to be sensitive biomarkers confirmed by follow-up cohort study.

背景和目的 已发现山梨醇脱氢酶(SORD)基因的双叶变体是常染色体隐性(AR)周围神经病(PN)的遗传病因,表现为夏科-玛丽-牙病 2 型(CMT2)或远端遗传性运动神经病(dHMN)。我们的目的是观察一组 SORD 相关 PN(SORD-PN)患者的遗传和临床谱系。 方法 共有 107 名 AR 或散发性 CMT2/dHMN 患者接受了全外显子组测序的分子诊断和随后的 Sanger 测序验证。收集并分析了 SORD-PN 的表型数据。 结果 107 例患者中有 11 例(10.28%)被确定为 SORD-PN,其中包括 4 例 CMT2 患者和 7 例 dHMN 患者。F-d3 中的 SORD 变异 c.210 T > G;p.His70Gln 最早被报道,随后的分析表明该变异导致 SORD 酶功能丧失。在 SORD-PN 患者中经常发现亚临床肌肉受累的证据,包括 10 例患者血清肌酸激酶(CK)水平轻度至中度升高,1 例患者出现肌源性电生理改变,5 例患者在接受下肢核磁共振成像检查时出现肌肉水肿。SORD-PN 患者的空腹血清山梨醇水平(9.69 ± 1.07 mg/L)是健康杂合子受试者(0.11 ± 0.01 mg/L)的 88 倍,是健康对照组(0.07 ± 0.02 mg/L)的 138 倍。 解释 发现了新型 SORD 变异 c.210 T > G;p.His70Gln 和亚临床肌肉受累的证据,这扩大了 SORD-PN 的遗传和临床范围。亚临床肌肉受累可能是一种常见但容易被忽视的临床特征。随访队列研究证实,血清肌酸激酶和空腹血清山梨醇水平有望成为敏感的生物标志物。
{"title":"Expanding the genetic and clinical spectrum of SORD-related peripheral neuropathy by reporting a novel variant c.210T>G and evidence of subclinical muscle involvement","authors":"Lu Li,&nbsp;Yongzhi Xie,&nbsp;Sen Zeng,&nbsp;Xiaobo Li,&nbsp;Zhiqiang Lin,&nbsp;Shunxiang Huang,&nbsp;Huadong Zhao,&nbsp;Wanqian Cao,&nbsp;Lei Liu,&nbsp;Jun Liu,&nbsp;Pengfei Rong,&nbsp;Ruxu Zhang","doi":"10.1111/jns.12591","DOIUrl":"10.1111/jns.12591","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Biallelic variants in the sorbitol dehydrogenase (<i>SORD</i>) gene have been identified as the genetic cause of autosomal recessive (AR) peripheral neuropathy (PN) manifesting as Charcot–Marie–Tooth disease type 2 (CMT2) or distal hereditary motor neuropathy (dHMN). We aim to observe the genetic and clinical spectrum of a cohort of patients with SORD-related PN (SORD-PN).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 107 patients with AR or sporadic CMT2/dHMN underwent molecular diagnosis by whole-exome sequencing and subsequent Sanger sequencing validation. Available phenotypic data for SORD-PN were collected and analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Eleven (10.28%) of 107 patients were identified as SORD-PN, including four with CMT2 and seven with dHMN. The <i>SORD</i> variant c.210 T &gt; G;p.His70Gln in F-d3 was firstly reported and subsequent analysis showed that it resulted in loss of SORD enzyme function. Evidence of subclinical muscle involvement was frequently detected in patients with SORD-PN, including mildly to moderately elevated serum creatine kinase (CK) levels in 10 patients, myogenic electrophysiological changes in one patient, and muscle edema in five patients undergoing lower extremity MRI. Fasting serum sorbitol level was 88-fold higher in SORD-PN patients (9.69 ± 1.07 mg/L) than in healthy heterozygous subjects (0.11 ± 0.01 mg/L) and 138-fold higher than in healthy controls (0.07 ± 0.02 mg/L).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>The novel <i>SORD</i> variant c.210 T &gt; G;p.His70Gln and evidence of subclinical muscle involvement were identified, which expanded the genetic and clinical spectrum of SORD-PN. Subclinical muscle involvement might be a common but easily overlooked clinical feature. The serum CK and fasting serum sorbitol levels were expected to be sensitive biomarkers confirmed by follow-up cohort study.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"28 4","pages":"608-613"},"PeriodicalIF":3.8,"publicationDate":"2023-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10037154","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
Genetic, electrophysiological, and pathological studies on patients with SCN9A-related pain disorders 对 SCN9A 相关疼痛疾病患者的遗传学、电生理学和病理学研究
IF 3.8 3区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2023-08-09 DOI: 10.1111/jns.12590
Jun-Hui Yuan, Xiaoyang Cheng, Eiji Matsuura, Yujiro Higuchi, Masahiro Ando, Akihiro Hashiguchi, Akiko Yoshimura, Ryo Nakachi, Jun Mine, Takeshi Taketani, Kenichi Maeda, Saori Kawakami, Ryutaro Kira, Shoko Tanaka, Kazuaki Kanai, Fadia Dib-Hajj, Sulayman D. Dib-Hajj, Stephen G. Waxman, Hiroshi Takashima

Background and Aims

Voltage-gated sodium channel Nav1.7, encoded by the SCN9A gene, has been linked to diverse painful peripheral neuropathies, represented by the inherited erythromelalgia (EM) and paroxysmal extreme pain disorder (PEPD). The aim of this study was to determine the genetic etiology of patients experiencing neuropathic pain, and shed light on the underlying pathogenesis.

Methods

We enrolled eight patients presenting with early-onset painful peripheral neuropathies, consisting of six cases exhibiting EM/EM-like disorders and two cases clinically diagnosed with PEPD. We conducted a gene-panel sequencing targeting 18 genes associated with hereditary sensory and/or autonomic neuropathy. We introduced novel SCN9A mutation (F1624S) into a GFP-2A-Nav1.7rNS plasmid, and the constructs were then transiently transfected into HEK293 cells. We characterized both wild-type and F1624S Nav1.7 channels using an automated high-throughput patch-clamp system.

Results

From two patients displaying EM-like/EM phenotypes, we identified two SCN9A mutations, I136V and P1308L. Among two patients diagnosed with PEPD, we found two additional mutations in SCN9A, F1624S (novel) and A1632E. Patch-clamp analysis of Nav1.7-F1624S revealed depolarizing shifts in both steady-state fast inactivation (17.4 mV, p < .001) and slow inactivation (5.5 mV, p < .001), but no effect on channel activation was observed.

Interpretation

Clinical features observed in our patients broaden the phenotypic spectrum of SCN9A-related pain disorders, and the electrophysiological analysis enriches the understanding of genotype–phenotype association caused by Nav1.7 gain-of-function mutations.

背景和目的 由 SCN9A 基因编码的电压门控钠通道 Nav1.7 与多种疼痛性周围神经病有关,其中以遗传性红斑性肢痛症(EM)和阵发性极度疼痛症(PEPD)为代表。本研究旨在确定神经病理性疼痛患者的遗传病因,并揭示其潜在的发病机制。 方法 我们招募了八名早发性疼痛性周围神经病患者,其中六名表现为 EM/EM 类疾病,两名临床诊断为 PEPD。我们对与遗传性感觉和/或自主神经病变相关的18个基因进行了基因组测序。我们将新型 SCN9A 突变(F1624S)导入 GFP-2A-Nav1.7rNS 质粒,然后将构建体瞬时转染到 HEK293 细胞中。我们使用自动高通量膜片钳系统鉴定了野生型和 F1624S Nav1.7 通道。 结果 我们从两名表现出 EM-like/EM 表型的患者中发现了两个 SCN9A 突变,即 I136V 和 P1308L。在两名被诊断为 PEPD 的患者中,我们发现了 SCN9A 的另外两个突变,即 F1624S(新型)和 A1632E。对 Nav1.7-F1624S 的贴片钳分析表明,稳态快速失活(17.4 mV,p < .001)和慢速失活(5.5 mV,p < .001)均有去极化偏移,但对通道激活没有影响。 解释 我们在患者身上观察到的临床特征拓宽了 SCN9A 相关疼痛疾病的表型谱,电生理分析丰富了对 Nav1.7 功能增益突变引起的基因型-表型关联的理解。
{"title":"Genetic, electrophysiological, and pathological studies on patients with SCN9A-related pain disorders","authors":"Jun-Hui Yuan,&nbsp;Xiaoyang Cheng,&nbsp;Eiji Matsuura,&nbsp;Yujiro Higuchi,&nbsp;Masahiro Ando,&nbsp;Akihiro Hashiguchi,&nbsp;Akiko Yoshimura,&nbsp;Ryo Nakachi,&nbsp;Jun Mine,&nbsp;Takeshi Taketani,&nbsp;Kenichi Maeda,&nbsp;Saori Kawakami,&nbsp;Ryutaro Kira,&nbsp;Shoko Tanaka,&nbsp;Kazuaki Kanai,&nbsp;Fadia Dib-Hajj,&nbsp;Sulayman D. Dib-Hajj,&nbsp;Stephen G. Waxman,&nbsp;Hiroshi Takashima","doi":"10.1111/jns.12590","DOIUrl":"10.1111/jns.12590","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Voltage-gated sodium channel Nav1.7, encoded by the <i>SCN9A</i> gene, has been linked to diverse painful peripheral neuropathies, represented by the inherited erythromelalgia (EM) and paroxysmal extreme pain disorder (PEPD). The aim of this study was to determine the genetic etiology of patients experiencing neuropathic pain, and shed light on the underlying pathogenesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We enrolled eight patients presenting with early-onset painful peripheral neuropathies, consisting of six cases exhibiting EM/EM-like disorders and two cases clinically diagnosed with PEPD. We conducted a gene-panel sequencing targeting 18 genes associated with hereditary sensory and/or autonomic neuropathy. We introduced novel <i>SCN9A</i> mutation (F1624S) into a GFP-2A-Nav1.7rNS plasmid, and the constructs were then transiently transfected into HEK293 cells. We characterized both wild-type and F1624S Nav1.7 channels using an automated high-throughput patch-clamp system.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>From two patients displaying EM-like/EM phenotypes, we identified two <i>SCN9A</i> mutations, I136V and P1308L. Among two patients diagnosed with PEPD, we found two additional mutations in <i>SCN9A</i>, F1624S (novel) and A1632E. Patch-clamp analysis of Nav1.7-F1624S revealed depolarizing shifts in both steady-state fast inactivation (17.4 mV, <i>p</i> &lt; .001) and slow inactivation (5.5 mV, <i>p</i> &lt; .001), but no effect on channel activation was observed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Clinical features observed in our patients broaden the phenotypic spectrum of <i>SCN9A</i>-related pain disorders, and the electrophysiological analysis enriches the understanding of genotype–phenotype association caused by Nav1.7 gain-of-function mutations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"28 4","pages":"597-607"},"PeriodicalIF":3.8,"publicationDate":"2023-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10021484","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
Ophthalmological involvement in wild-type transthyretin amyloidosis: A multimodal imaging study 野生型转甲状腺素淀粉样变性的眼科受累:多模态成像研究
IF 3.8 3区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2023-08-08 DOI: 10.1111/jns.12589
Luisa Frizziero, Alessandro Salvalaggio, Eleonora Cosmo, Alberto Cipriani, Edoardo Midena, Chiara Briani

Background and Aims

Ophthalmological abnormalities have been reported in hereditary transthyretin-related amyloidosis (ATTRv, v for variant) but not in wild-type transthyretin-related amyloidosis (ATTRwt).

Methods

Patients with ATTRwt, ATTRv, and light chain amyloidosis (AL) and healthy subjects (controls) underwent complete eye examination, including optical coherence tomography (OCT), OCT angiography (OCTA), and in vivo corneal confocal microscopy (CCM).

Results

Seventeen ATTRwt, nine ATTRv, two ATTRv carriers, and seven AL patients were enrolled. Compared with other groups, ATTRwt patients had 10 letters lower visual acuity and a higher prevalence of glaucoma, cataract, and retinal pigment epithelium alterations. In the whole group of patients, especially in ATTRwt, we observed (1) a reduced corneal nerve fiber length and more tortuous stromal nerves at CCM, (2) a reduced macular volume and peripapillary nerve fiber layer thickness at OCT, and (3) impairment of peripapillary and macular vascularization at OCTA.

Interpretation

Ophthalmological abnormalities are common in ATTRwt, significantly impairing visual acuity. Noninvasive imaging modalities allow for the identification of small nerve fibers and small vessel damage, which may represent further warning signs for early diagnosis of ATTRwt.

背景和目的 据报道,遗传性转甲状腺素相关淀粉样变性病(ATTRv,v表示变异型)会出现眼部异常,而野生型转甲状腺素相关淀粉样变性病(ATTRwt)不会出现眼部异常。 方法 对 ATTRwt、ATTRv 和轻链淀粉样变性(AL)患者以及健康受试者(对照组)进行全面的眼部检查,包括光学相干断层扫描(OCT)、OCT 血管造影术(OCTA)和活体角膜共聚焦显微镜(CCM)。 结果 共纳入 17 名 ATTRwt 患者、9 名 ATTRv 患者、2 名 ATTRv 携带者和 7 名 AL 患者。与其他组别相比,ATTRwt 患者的视力要低 10 个字母,青光眼、白内障和视网膜色素上皮改变的发病率较高。在整组患者中,尤其是在 ATTRwt 患者中,我们观察到:(1)CCM 观察到角膜神经纤维长度减少,基质神经更加迂曲;(2)OCT 观察到黄斑体积和毛细血管周围神经纤维层厚度减少;(3)OCTA 观察到毛细血管周围和黄斑血管受损。 解释 ATTRwt 常见眼科异常,严重影响视力。无创成像模式可识别小神经纤维和小血管损伤,这可能是早期诊断 ATTRwt 的进一步预警信号。
{"title":"Ophthalmological involvement in wild-type transthyretin amyloidosis: A multimodal imaging study","authors":"Luisa Frizziero,&nbsp;Alessandro Salvalaggio,&nbsp;Eleonora Cosmo,&nbsp;Alberto Cipriani,&nbsp;Edoardo Midena,&nbsp;Chiara Briani","doi":"10.1111/jns.12589","DOIUrl":"10.1111/jns.12589","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Ophthalmological abnormalities have been reported in hereditary transthyretin-related amyloidosis (ATTRv, v for variant) but not in wild-type transthyretin-related amyloidosis (ATTRwt).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients with ATTRwt, ATTRv, and light chain amyloidosis (AL) and healthy subjects (controls) underwent complete eye examination, including optical coherence tomography (OCT), OCT angiography (OCTA), and in vivo corneal confocal microscopy (CCM).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Seventeen ATTRwt, nine ATTRv, two ATTRv carriers, and seven AL patients were enrolled. Compared with other groups, ATTRwt patients had 10 letters lower visual acuity and a higher prevalence of glaucoma, cataract, and retinal pigment epithelium alterations. In the whole group of patients, especially in ATTRwt, we observed (1) a reduced corneal nerve fiber length and more tortuous stromal nerves at CCM, (2) a reduced macular volume and peripapillary nerve fiber layer thickness at OCT, and (3) impairment of peripapillary and macular vascularization at OCTA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Ophthalmological abnormalities are common in ATTRwt, significantly impairing visual acuity. Noninvasive imaging modalities allow for the identification of small nerve fibers and small vessel damage, which may represent further warning signs for early diagnosis of ATTRwt.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"28 4","pages":"586-596"},"PeriodicalIF":3.8,"publicationDate":"2023-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.12589","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10135095","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
期刊
Journal of the Peripheral Nervous System
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1