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Correction to “Earlier diagnosis of peripheral neuropathy in primary care: A call to action” 更正 "基层医疗机构更早地诊断周围神经病变:行动呼吁"。
IF 3.9 3区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-14 DOI: 10.1111/jns.12652

Gad H, Kalra S, Pinzon R, et al. Earlier diagnosis of peripheral neuropathy in primary care: a call to action. J Peripher Nerv Syst. 2024;29(1):28-37. doi:10.1111/jns.12613

It has come to our attention that there was an error in the spelling of one of the co-author's names in the above article. The correct spelling should be Rey-an Nino Garcia instead of Rey-an Nino Gracia. The article has been corrected.

We apologize for this error.

Gad H、Kalra S、Pinzon R 等人.初级保健中周围神经病变的早期诊断:行动呼吁。J Peripher Nerv Syst.2024;29(1):28-37.DOI:10.1111/jns.12613我们注意到,上述文章中一位合著者的姓名拼写有误。正确的拼写应该是 Rey-an Nino Garcia,而不是 Rey-an Nino Gracia。我们对此错误深表歉意。
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引用次数: 0
Diagnostic and clinical utility of comprehensive multigene panel testing for patients with neuropathy 神经病变患者多基因综合面板检测的诊断和临床实用性。
IF 3.9 3区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-14 DOI: 10.1111/jns.12651
Jennifer Roggenbuck, Ana Morales, Colin A. Ellis, Laynie Dratch, Molly Stetler, Christopher A. Tan, Brianna Bucknor, Kathryn E. Hatchell, Swaroop Aradhya, Edward D. Esplin, Yi-Lee Ting, Steven S. Scherer

Background and Aims

Prior to next-generation sequencing (NGS), the evaluation of a patient with neuropathy typically consisted of screening for acquired causes, followed by clinical genetic testing of PMP22, MFN2, GJB1, and MPZ in patients with a positive family history and symptom onset prior to age 50. In this study, we examined the clinical utility of NGS in a large cohort of patients analyzed in a commercial laboratory.

Methods

A cohort of 6849 adult patients underwent clinician-ordered peripheral neuropathy multigene panel testing ranging from 66 to 111 genes that included NGS and intragenic deletion/duplication analysis.

Results

A molecular diagnosis was identified for 8.4% of the cohort (n = 573/6849). Variants in PMP22, MFN2, GJB1, MPZ, and TTR accounted for 73.8% of molecular diagnoses. Results had potential clinical actionability for 398 (69.5%) patients. Our results suggest that 225/573 (39.3%) of molecular diagnoses and 113/398 (28.4%) of clinical interventions would have been missed if the testing approach had been restricted to older guidelines.

Interpretation

Our results highlight the need for expanded genetic testing guidelines that account for the increased number of genes associated with hereditary neuropathy, address the overlap of acquired and hereditary neuropathy, and provide broader access to genetic diagnosis for patients.

背景和目的:在使用新一代测序技术(NGS)之前,对神经病患者的评估通常包括筛查获得性病因,然后对有阳性家族史且在 50 岁之前发病的患者进行 PMP22、MFN2、GJB1 和 MPZ 的临床基因检测。在本研究中,我们在商业实验室分析的一大批患者中考察了 NGS 的临床实用性:6849 名成年患者接受了临床医生要求的周围神经病变多基因组检测,检测范围从 66 个基因到 111 个基因,包括 NGS 和基因内缺失/重复分析:结果:8.4%的患者(n = 573/6849)得到了分子诊断。PMP22、MFN2、GJB1、MPZ 和 TTR 的变异占分子诊断的 73.8%。398例(69.5%)患者的结果具有潜在的临床可操作性。我们的结果表明,如果检测方法仅限于旧版指南,将错过 225/573 例(39.3%)分子诊断和 113/398 例(28.4%)临床干预:我们的研究结果凸显了扩大基因检测指南范围的必要性,这些指南应考虑到与遗传性神经病相关基因数量的增加,解决获得性和遗传性神经病的重叠问题,并为患者提供更广泛的基因诊断途径。
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引用次数: 0
Initial findings using high-resolution magnetic resonance imaging for visualisation of the sural nerve and surrounding anatomy in healthy volunteers at 7 Tesla 使用高分辨率磁共振成像在 7 特斯拉下观察健康志愿者的硬脊膜神经和周围解剖结构的初步发现。
IF 3.9 3区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-07-26 DOI: 10.1111/jns.12645
Amy R. McDowell, Laura Zambreanu, Hamza A. Salhab, Carolynne M. Doherty, Philippa Bridgen, Pete Lally, Sachit Shah, Zimu Huo, Stephen J. Wastling, Tarek Yousry, Jasper Morrow, John S. Thornton, Michael P. Lunn

Background and Aims

Histopathological diagnosis is the gold standard in many acquired inflammatory, infiltrative and amyloid based peripheral nerve diseases and a sensory nerve biopsy of sural or superficial peroneal nerve is favoured where a biopsy is deemed necessary. The ability to determine nerve pathology by high-resolution imaging techniques resolving anatomy and imaging characteristics might improve diagnosis and obviate the need for biopsy in some. The sural nerve is anatomically variable and occasionally adjacent vessels can be sent for analysis in error. Knowing the exact position and relationships of the nerve prior to surgery could be clinically useful and thus reliably resolving nerve position has some utility.

Methods

7T images of eight healthy volunteers' (HV) right ankle were acquired in a pilot study using a double-echo in steady-state sequence for high-resolution anatomy images. Magnetic Transfer Ratio images were acquired of the same area. Systematic scoring of the sural, tibial and deep peroneal nerve around the surgical landmark 7 cm from the lateral malleolus was performed (number of fascicles, area in voxels and mm2, diameter and location relative to nearby vessels and muscles).

Results

The sural and tibial nerves were visualised in the high-resolution double-echo in steady-state (DESS) image in all HV. The deep peroneal nerve was not always visualised at level of interest. The MTR values were tightly grouped except in the sural nerve where the nerve was not visualised in two HV. The sural nerve location was found to be variable (e.g., lateral or medial to, or crossing behind, or found positioned directly posterior to the saphenous vein).

Interpretation

High-resolution high-field images have excellent visualisation of the sural nerve and would give surgeons prior knowledge of the position before surgery. Basic imaging characteristics of the sural nerve can be acquired, but more detailed imaging characteristics are not easily evaluable in the very small sural and further developments and specific studies are required for any diagnostic utility at 7T.

背景和目的:组织病理学诊断是许多获得性炎症、浸润性和淀粉样变性周围神经疾病的金标准,在认为有必要进行活检的情况下,应首选对硬神经或腓浅神经进行感觉神经活检。通过高分辨率成像技术来确定神经病变的解剖和成像特征可能会改善诊断,并使某些患者无需进行活检。鞍神经在解剖学上是多变的,偶尔会错误地将邻近的血管送去分析。手术前了解神经的确切位置和关系可能对临床有用,因此可靠地确定神经位置具有一定的实用性。方法:在一项试验性研究中,使用稳态双回波序列获取了八名健康志愿者(HV)右踝关节的 7T 图像,以获得高分辨率解剖图像。同时还采集了同一区域的磁转移比图像。在距外侧踝骨 7 厘米的手术标志周围对硬神经、胫神经和腓深神经进行了系统评分(筋束数量、体素和平方毫米面积、直径以及与附近血管和肌肉的相对位置):在所有 HV 的高分辨率稳态双回波(DESS)图像中都能看到鞍神经和胫神经。腓深神经并不总能在感兴趣水平上显示出来。除了在两个 HV 中未观察到硬脊膜神经外,其他 MTR 值都是紧密分组的。腓总神经的位置可变(例如,位于隐静脉的外侧或内侧,或穿过隐静脉的后方,或位于隐静脉的正后方):解读:高分辨率的高场图像可清晰显示腓肠神经,使外科医生在手术前就能预先了解其位置。可以获得腓肠神经的基本成像特征,但在非常小的腓肠神经中不容易评估更详细的成像特征,需要进一步开发和具体研究才能在 7T 下进行诊断。
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引用次数: 0
Correction to ‘Serum neurofilament light chain measurements following nerve trauma’ 神经创伤后血清神经丝轻链的测量结果 "的更正。
IF 3.9 3区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-07-11 DOI: 10.1111/jns.12642

Wilcox M, Rayner MLD, Guillemot-Legris O, Platt I, Brown H, Quick T, Phillips JB Serum neurofilament light chain measurements following nerve trauma. J Peripher Nerv Syst. 2023;28(3):500–507. doi:10.1111/jns.12576

There was an error in the analysis of serum NfL data that resulted in the values in Figure 1, Table 1 and Results being expressed incorrectly as 40-fold lower than their correct concentration. The ‘Serum NfL analysis’ section of the Methods should read ‘Serum NfL concentration was measured using the Simoa HD-X Analyser (Quanterix, Billerica, MA) with a Neurology 4-plex B kit (item number: 103345). All samples were randomised across the plates and run in duplicate. All samples measured were above the lower limit of detection (0.0962 pg/mL) with a mean coefficient of variation of 13.2% between duplicates. Intra- and inter-plate coefficients of variation, monitored using 2-4 pooled human internal control samples across each plate, were <10%’. not ‘NfL levels in serum were measured using a SIMOA® SR-X analyser (Quanterix Corporation, Massachusetts) with a SIMOA® NF-light Advantage (SR-X) Kit (Quanterix, No. 103400) according to protocols well described elsewhere (O'Brien, et al., 2021). All samples were run in duplicate and analysers were blinded to the experimental conditions. All samples measured above the lower limit of detection (0.038 pg/mL) with a mean coefficient of variation of 9.15% between duplicates. Furthermore, two control samples were run on each place with a mean coefficient of variation of 6.90%’.

New versions of Figure 1 and Table 1 have been provided. In addition, the second line of the Results section should read 20.33 ± 8.98 pg/mL rather than 0.50 ± 0.2 pg/mL. The third line of the Discussion section should read 20 pg/mL rather than 0.50 pg/mL.

We apologise for this error.

Wilcox M、Rayner MLD、Guillemot-Legris O、Platt I、Brown H、Quick T、Phillips JB 神经创伤后的血清神经丝轻链测量。J Peripher Nerv Syst.doi:10.1111/jns.12576在分析血清神经丝轻链数据时出现错误,导致图 1、表 1 和结果中的数值被错误地表示为比其正确浓度低 40 倍。方法》中的 "血清 NfL 分析 "部分应为 "使用 Simoa HD-X 分析仪(Quanterix, Billerica, MA)和神经学 4-plex B 试剂盒(货号:103345)测量血清 NfL 浓度。所有样品在平板上随机排列,一式两份。所有测定的样品均高于检测下限(0.0962 pg/mL),重复样品之间的平均变异系数为 13.2%。使用每个板上的 2-4 个集合人类内部对照样本监测板内和板间变异系数,结果均为 <10%'。而非'使用 SIMOA® SR-X 分析仪(Quanterix Corporation,马萨诸塞州)和 SIMOA® NF-light Advantage (SR-X) 试剂盒(Quanterix,编号 103400),按照其他地方详细描述的方案(O'Brien 等人,2021 年)测量血清中的 NfL 水平。所有样品均一式两份,分析人员对实验条件保密。所有样本的测量值均高于检测下限(0.038 pg/mL),重复样本之间的平均变异系数为 9.15%。图 1 和表 1 提供了新版本。此外,结果部分第二行应为 20.33 ± 8.98 pg/mL,而不是 0.50 ± 0.2 pg/mL。讨论部分第三行应为 20 pg/mL,而不是 0.50 pg/mL。
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引用次数: 0
Efficacy and safety of eculizumab in Guillain-Barré syndrome: A phase 3, multicenter, double-blind, randomized, placebo-controlled clinical trial 依库珠单抗治疗格林-巴利综合征的有效性和安全性:3期多中心、双盲、随机、安慰剂对照临床试验。
IF 3.9 3区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-07-10 DOI: 10.1111/jns.12646
Satoshi Kuwabara, Susumu Kusunoki, Motoi Kuwahara, Yoshihisa Yamano, Yoichiro Nishida, Hirokazu Ishida, Tomoyuki Kasuya, Erik Kupperman, Qun Lin, Glen Frick, Sonoko Misawa

Background and Aims

Guillain-Barré syndrome (GBS) is an acute, self-limited, immune-mediated peripheral neuropathy. Current treatments for GBS include intravenous immunoglobulin (IVIg) and plasma exchange, which may not sufficiently benefit severely affected patients. This study evaluated the efficacy and safety of eculizumab add-on therapy to IVIg (standard-of-care treatment) in patients with severe GBS.

Methods

This phase 3, multicenter, double-blind, randomized, placebo-controlled clinical trial (NCT04752566), enrolled Japanese adults (age ≥ 18 years) with severe GBS (Hughes functional grade [FG] score FG3 or FG4/FG5 within 2 weeks of onset of GBS). Participants were randomized 2:1 to receive intravenous infusion of eculizumab or placebo (once weekly for 4 weeks) with IVIg treatment with 20 weeks of follow-up. Primary efficacy endpoint was the time to first reach FG score ≤1 (able to run). Key secondary endpoints were proportion of participants achieving FG ≤1 at weeks 8 and 24 and FG improvement ≥3 at week 24. Pharmacodynamic analysis of serum free C5 concentration over time was performed. Safety was evaluated.

Results

The analysis included 57 participants (eculizumab, n = 37; placebo, n = 20). Primary endpoint was not achieved (hazard ratio, 0.9; 95% CI, 0.45–1.97; p = .89). Key secondary endpoints did not reach statistical significance. Serum C5 concentration was reduced by 99.99% at 1 h postdose and sustained to week 5 but returned to baseline at the end of follow-up period. No new safety signals for eculizumab were identified.

Interpretation

Although well tolerated, eculizumab treatment did not show significant effects on motor function recovery compared to placebo in patients with GBS.

背景和目的:吉兰-巴雷综合征(GBS)是一种急性、自限性、免疫介导的周围神经病。目前治疗吉兰-巴雷综合征的方法包括静脉注射免疫球蛋白(IVIg)和血浆置换,但这两种方法可能无法使重症患者充分受益。本研究评估了依库珠单抗作为IVIg(标准疗法)的附加疗法对重症GBS患者的疗效和安全性:这项 3 期、多中心、双盲、随机、安慰剂对照临床试验(NCT04752566)招募了患有重症 GBS(GBS 发病 2 周内休斯功能分级 [FG] 评分 FG3 或 FG4/FG5)的日本成人(年龄≥ 18 岁)。参与者按 2:1 随机分配接受静脉输注 eculizumab 或安慰剂(每周一次,共 4 周),并接受 20 周的 IVIg 治疗。主要疗效终点是首次达到FG评分≤1(能跑步)的时间。主要次要终点是第8周和第24周达到FG≤1的参与者比例,以及第24周FG改善≥3。对血清游离 C5 浓度随时间变化进行药效学分析。对安全性进行了评估:分析包括57名参与者(依库珠单抗,n = 37;安慰剂,n = 20)。主要终点未达到(危险比,0.9;95% CI,0.45-1.97;P = .89)。主要次要终点未达到统计学意义。用药后1小时血清C5浓度降低了99.99%,并持续到第5周,但在随访期结束时又恢复到基线水平。未发现依库珠单抗有新的安全性信号:尽管耐受性良好,但与安慰剂相比,依库珠单抗治疗对GBS患者运动功能的恢复没有显著影响。
{"title":"Efficacy and safety of eculizumab in Guillain-Barré syndrome: A phase 3, multicenter, double-blind, randomized, placebo-controlled clinical trial","authors":"Satoshi Kuwabara,&nbsp;Susumu Kusunoki,&nbsp;Motoi Kuwahara,&nbsp;Yoshihisa Yamano,&nbsp;Yoichiro Nishida,&nbsp;Hirokazu Ishida,&nbsp;Tomoyuki Kasuya,&nbsp;Erik Kupperman,&nbsp;Qun Lin,&nbsp;Glen Frick,&nbsp;Sonoko Misawa","doi":"10.1111/jns.12646","DOIUrl":"10.1111/jns.12646","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Guillain-Barré syndrome (GBS) is an acute, self-limited, immune-mediated peripheral neuropathy. Current treatments for GBS include intravenous immunoglobulin (IVIg) and plasma exchange, which may not sufficiently benefit severely affected patients. This study evaluated the efficacy and safety of eculizumab add-on therapy to IVIg (standard-of-care treatment) in patients with severe GBS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This phase 3, multicenter, double-blind, randomized, placebo-controlled clinical trial (NCT04752566), enrolled Japanese adults (age ≥ 18 years) with severe GBS (Hughes functional grade [FG] score FG3 or FG4/FG5 within 2 weeks of onset of GBS). Participants were randomized 2:1 to receive intravenous infusion of eculizumab or placebo (once weekly for 4 weeks) with IVIg treatment with 20 weeks of follow-up. Primary efficacy endpoint was the time to first reach FG score ≤1 (able to run). Key secondary endpoints were proportion of participants achieving FG ≤1 at weeks 8 and 24 and FG improvement ≥3 at week 24. Pharmacodynamic analysis of serum free C5 concentration over time was performed. Safety was evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The analysis included 57 participants (eculizumab, <i>n</i> = 37; placebo, <i>n</i> = 20). Primary endpoint was not achieved (hazard ratio, 0.9; 95% CI, 0.45–1.97; <i>p</i> = .89). Key secondary endpoints did not reach statistical significance. Serum C5 concentration was reduced by 99.99% at 1 h postdose and sustained to week 5 but returned to baseline at the end of follow-up period. No new safety signals for eculizumab were identified.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Although well tolerated, eculizumab treatment did not show significant effects on motor function recovery compared to placebo in patients with GBS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.12646","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580101","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
Clinical, histologic, and immunologic signatures of Small Fiber Neuropathy in Systemic Lupus Erythematosus 系统性红斑狼疮小纤维神经病的临床、组织学和免疫学特征。
IF 3.9 3区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-07-09 DOI: 10.1111/jns.12644
Eleonora Galosi, Carmelo Pirone, Fulvia Ceccarelli, Nicoletta Esposito, Pietro Falco, Martina Leopizzi, Valeria Di Maio, Lorenzo Tramontana, Gianfranco De Stefano, Giuseppe Di Pietro, Giulia Di Stefano, Cristina Garufi, Caterina Leone, Francesco Natalucci, Valeria Orefice, Cristiano Alessandri, Francesca Romana Spinelli, Andrea Truini, Fabrizio Conti

Background and Objectives

Systemic Lupus Erythematosus (SLE) often causes damage to small nerve fibers, leading to distressing painful and autonomic symptoms. Despite this, Small Fiber Neuropathy (SFN) remains an underrecognized complication for SLE patients. In this cross-sectional study, we aimed to assess SFN in patients with SLE and to explore its correlations with immunologic disease features and clinical manifestations.

Methods

We recruited 50 SLE patients (1 male to 12.5 females, aged 20–80 years) reporting painful disturbances. We conducted a comprehensive clinical and neurophysiological evaluation, using Nerve Conduction Studies and Quantitative Sensory Testing. Additionally, we carried out an extensive laboratory assessment of disease-related serological parameters. We also performed a thorough skin biopsy analysis, investigating somatic and autonomic innervation while detecting complement and inflammatory cell infiltrates within the skin.

Results

Out of 50 patients, 19 were diagnosed with SFN, primarily characterized by a non-length-dependent distribution; 7 had a mixed neuropathy, with both large and small fiber involvement. Patients with SFN were younger than patients with a mixed neuropathy (p = .0143); furthermore, they were more likely to have a history of hypocomplementemia (p = .0058) and to be treated with cyclosporine A (p = .0053) compared to patients without neuropathy. However, there were no significant differences in painful and autonomic symptoms between patients with and without SFN.

Discussion

This study highlights the relevant frequency of SFN with a non-length-dependent distribution among SLE patients experiencing painful symptoms. Indeed, SFN emerges as an early manifestation of SLE-related neuropathy and is closely associated with hypocomplementemia, suggesting a potential pathogenic role of the complement system. Moreover, SFN may be influenced by disease-modifying therapies. However, the precise role of SFN in shaping painful and autonomic symptoms in patients with SLE remains to be fully elucidated.

背景和目的:系统性红斑狼疮(SLE)常常会对小神经纤维造成损伤,导致令人痛苦的疼痛和自主神经症状。尽管如此,小神经纤维病变(SFN)仍然是系统性红斑狼疮患者未得到充分认识的并发症。在这项横断面研究中,我们旨在评估系统性红斑狼疮患者的小纤维神经病变,并探讨其与免疫学疾病特征和临床表现的相关性:方法:我们招募了50名报告有疼痛障碍的系统性红斑狼疮患者(男性1人,女性12.5人,年龄20-80岁)。我们使用神经传导研究和定量感觉测试对患者进行了全面的临床和神经生理学评估。此外,我们还对与疾病相关的血清学参数进行了广泛的实验室评估。我们还进行了全面的皮肤活检分析,研究躯体和自主神经支配,同时检测皮肤内的补体和炎性细胞浸润:在 50 名患者中,19 人被确诊为 SFN,其主要特征是非长度依赖性分布;7 人患有混合型神经病,大纤维和小纤维均受累。与混合型神经病变患者相比,SFN 患者更年轻(p = .0143);此外,与无神经病变患者相比,SFN 患者更可能有低补体血症病史(p = .0058),也更可能接受环孢素 A 治疗(p = .0053)。但是,有SFN和没有SFN的患者在疼痛和自主神经症状方面没有明显差异:讨论:本研究强调了在出现疼痛症状的系统性红斑狼疮患者中,SFN的发生率与长度无关。事实上,SFN 是系统性红斑狼疮相关神经病变的早期表现,与低补体血症密切相关,这表明补体系统具有潜在的致病作用。此外,SFN 还可能受到疾病改变疗法的影响。然而,SFN 在形成系统性红斑狼疮患者疼痛和自主神经症状方面的确切作用仍有待全面阐明。
{"title":"Clinical, histologic, and immunologic signatures of Small Fiber Neuropathy in Systemic Lupus Erythematosus","authors":"Eleonora Galosi,&nbsp;Carmelo Pirone,&nbsp;Fulvia Ceccarelli,&nbsp;Nicoletta Esposito,&nbsp;Pietro Falco,&nbsp;Martina Leopizzi,&nbsp;Valeria Di Maio,&nbsp;Lorenzo Tramontana,&nbsp;Gianfranco De Stefano,&nbsp;Giuseppe Di Pietro,&nbsp;Giulia Di Stefano,&nbsp;Cristina Garufi,&nbsp;Caterina Leone,&nbsp;Francesco Natalucci,&nbsp;Valeria Orefice,&nbsp;Cristiano Alessandri,&nbsp;Francesca Romana Spinelli,&nbsp;Andrea Truini,&nbsp;Fabrizio Conti","doi":"10.1111/jns.12644","DOIUrl":"10.1111/jns.12644","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Objectives</h3>\u0000 \u0000 <p>Systemic Lupus Erythematosus (SLE) often causes damage to small nerve fibers, leading to distressing painful and autonomic symptoms. Despite this, Small Fiber Neuropathy (SFN) remains an underrecognized complication for SLE patients. In this cross-sectional study, we aimed to assess SFN in patients with SLE and to explore its correlations with immunologic disease features and clinical manifestations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We recruited 50 SLE patients (1 male to 12.5 females, aged 20–80 years) reporting painful disturbances. We conducted a comprehensive clinical and neurophysiological evaluation, using Nerve Conduction Studies and Quantitative Sensory Testing. Additionally, we carried out an extensive laboratory assessment of disease-related serological parameters. We also performed a thorough skin biopsy analysis, investigating somatic and autonomic innervation while detecting complement and inflammatory cell infiltrates within the skin.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Out of 50 patients, 19 were diagnosed with SFN, primarily characterized by a non-length-dependent distribution; 7 had a mixed neuropathy, with both large and small fiber involvement. Patients with SFN were younger than patients with a mixed neuropathy (<i>p</i> = .0143); furthermore, they were more likely to have a history of hypocomplementemia (<i>p</i> = .0058) and to be treated with cyclosporine A (<i>p</i> = .0053) compared to patients without neuropathy. However, there were no significant differences in painful and autonomic symptoms between patients with and without SFN.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>This study highlights the relevant frequency of SFN with a non-length-dependent distribution among SLE patients experiencing painful symptoms. Indeed, SFN emerges as an early manifestation of SLE-related neuropathy and is closely associated with hypocomplementemia, suggesting a potential pathogenic role of the complement system. Moreover, SFN may be influenced by disease-modifying therapies. However, the precise role of SFN in shaping painful and autonomic symptoms in patients with SLE remains to be fully elucidated.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563602","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
Identification of cellular and noncellular components of mature intact human peripheral nerve 鉴定成熟完整人类周围神经的细胞和非细胞成分。
IF 3.9 3区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-07-07 DOI: 10.1111/jns.12643
Gabriela I. Aparicio, Jorge E. Quintero, Lauren Plum, Lingxiao Deng, Kristen Wanczyk, Miriam Henry, Evan Lynch, Michael Murphy, Greg A. Gerhardt, Craig G. van Horne, Paula V. Monje

Background and Aims

The goal of this study was to define basic constituents of the adult peripheral nervous system (PNS) using intact human nerve tissues.

Methods

We combined fluorescent and chromogenic immunostaining methods, myelin-selective fluorophores, and routine histological stains to identify common cellular and noncellular elements in aldehyde-fixed nerve tissue sections. We employed Schwann cell (SC)-specific markers, such as S100β, NGFR, Sox10, and myelin protein zero (MPZ), together with axonal, extracellular matrix (collagen IV, laminin, fibronectin), and fibroblast markers to assess the SC's relationship to myelin sheaths, axons, other cell types, and the acellular environment.

Results

Whereas S100β and Sox10 revealed mature SCs in the absence of other stains, discrimination between myelinating and non-myelinating (Remak) SCs required immunodetection of NGFR along with axonal and/or myelin markers. Surprisingly, our analysis of NGFR+ profiles uncovered the existence of at least 3 different novel populations of NGFR+/S100β− cells, herein referred to as nonglial cells, residing in the stroma and perivascular areas of all nerve compartments. An important proportion of the nerve's cellular content, including circa 30% of endoneurial cells, consisted of heterogenous S100β negative cells that were not associated with axons. Useful markers to identify the localization and diversity of nonglial cell types across different compartments were Thy1, CD34, SMA, and Glut1, a perineurial cell marker.

Interpretation

Our optimized methods revealed additional detailed information to update our understanding of the complexity and spatial orientation of PNS-resident cell types in humans.

背景和目的本研究的目的是利用完整的人类神经组织确定成人周围神经系统(PNS)的基本成分:我们结合了荧光和色原免疫染色法、髓鞘选择性荧光团和常规组织学染色法,以确定醛固定神经组织切片中常见的细胞和非细胞元素。我们采用许旺细胞(SC)特异性标记物,如S100β、NGFR、Sox10和髓鞘蛋白零(MPZ),以及轴突、细胞外基质(胶原蛋白IV、层粘连蛋白、纤维连接蛋白)和成纤维细胞标记物来评估SC与髓鞘、轴突、其他细胞类型和无细胞环境的关系:结果:在没有其他染色剂的情况下,S100β和Sox10能显示成熟的SC,而区分髓鞘化和非髓化(Remak)SC则需要免疫检测NGFR以及轴突和/或髓鞘标记物。令人惊奇的是,我们对 NGFR+ 图谱的分析发现,至少存在 3 种不同的新型 NGFR+/S100β- 细胞群,在此称为非神经细胞,它们驻留在所有神经区的基质和血管周围区域。神经细胞的重要组成部分,包括约30%的内膜细胞,由与轴突无关的异源S100β阴性细胞组成。Thy1、CD34、SMA和Glut1(神经周围细胞标志物)是识别不同区段非神经胶质细胞类型定位和多样性的有用标志物:我们的优化方法揭示了更多详细信息,更新了我们对人类 PNS 驻留细胞类型的复杂性和空间定位的认识。
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引用次数: 0
Corneal confocal microscopy detects early nerve regeneration after pharmacological and surgical interventions: Systematic review and meta-analysis 角膜共聚焦显微镜检测药物和手术干预后的早期神经再生:系统回顾和荟萃分析。
IF 3.9 3区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-06-18 DOI: 10.1111/jns.12641
Hoda Gad, Einas Elgassim, Ahamed Lebbe, Ross S. MacDonald, Areej Baraka, Ioannis N. Petropoulos, Georgios Ponirakis, Nada O. Ibrahim, Rayaz A. Malik

Corneal confocal microscopy (CCM) is an ophthalmic imaging technique that enables the identification of corneal nerve fibre degeneration and regeneration. To undertake a systematic review and meta-analysis of studies utilizing CCM to assess for corneal nerve regeneration after pharmacological and surgical interventions in patients with peripheral neuropathy. Databases (EMBASE [Ovid], PubMed, CENTRAL and Web of Science) were searched to summarize the evidence from randomized and non-randomized studies using CCM to detect corneal nerve regeneration after pharmacological and surgical interventions. Data synthesis was undertaken using RevMan web. Eighteen studies including 958 patients were included. CCM identified an early (1–8 months) and longer term (1–5 years) increase in corneal nerve measures in patients with peripheral neuropathy after pharmacological and surgical interventions. This meta-analysis confirms the utility of CCM to identify nerve regeneration following pharmacological and surgical interventions. It could be utilized to show a benefit in clinical trials of disease modifying therapies for peripheral neuropathy.

角膜共聚焦显微镜(CCM)是一种眼科成像技术,能够识别角膜神经纤维的变性和再生。对利用 CCM 评估周围神经病变患者药物和手术干预后角膜神经再生情况的研究进行系统回顾和荟萃分析。检索数据库(EMBASE [Ovid]、PubMed、CENTRAL 和 Web of Science),总结使用 CCM 检测药物和手术干预后角膜神经再生的随机和非随机研究的证据。使用 RevMan 网页进行了数据综合。共纳入 18 项研究,包括 958 名患者。CCM 发现,经过药物和手术干预后,周围神经病变患者的角膜神经指标在早期(1-8 个月)和长期(1-5 年)均有增加。这项荟萃分析证实了 CCM 在药物和手术干预后识别神经再生的实用性。在针对周围神经病变的疾病调整疗法的临床试验中,可以利用它来显示治疗效果。
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引用次数: 0
Monoclonal gammopathy-associated peripheral neuropathies: Uncovering pearls and challenges 单克隆抗体病相关周围神经病:发现珍珠与挑战。
IF 3.9 3区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-06-14 DOI: 10.1111/jns.12638
Trajano Aguiar Pires Gonçalves, Camila Derminio Donadel, Rodrigo Siqueira Soares Frezatti, Pedro Manoel Marques Garibaldi, Rodrigo T. Calado, Wilson Marques Junior, Pedro José Tomaselli

Monoclonal gammopathy-related peripheral neuropathies encompass a spectrum of clinical presentations in which the monoclonal protein directly damages the tissues, including the peripheral nervous system. Given the prevalence of both peripheral neuropathy and monoclonal gammopathy in the general population, these conditions may overlap in clinical practice, posing a challenge for clinicians in determining causality. Therefore, a comprehensive understanding of primary clinical syndromes and their neurophysiological patterns is of great importance for accurate differential diagnoses and effective treatment strategies. In this article, we examine the main forms of monoclonal gammopathies that affect the peripheral nerve. We explore the clinical and electrophysiological aspects and their correlation with each syndrome's corresponding monoclonal protein type. This knowledge is essential for healthcare professionals to diagnose better and manage patients presenting with monoclonal gammopathy-related peripheral nervous system involvement.

单克隆丙种球蛋白病相关周围神经病包括一系列临床表现,其中单克隆蛋白直接损害组织,包括周围神经系统。鉴于周围神经病变和单克隆抗体病在普通人群中的发病率较高,这些病症在临床实践中可能会出现重叠,给临床医生确定因果关系带来了挑战。因此,全面了解原发性临床综合征及其神经生理学模式对于准确鉴别诊断和有效治疗策略至关重要。在本文中,我们将探讨影响周围神经的单克隆丙种球蛋白病的主要形式。我们探讨了临床和电生理学方面的问题,以及它们与每种综合征的相应单克隆蛋白类型之间的相关性。这些知识对于医护人员更好地诊断和管理单克隆丙种球蛋白病相关周围神经系统受累的患者至关重要。
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引用次数: 0
The neurological core features of the infantile-onset multisystem neurologic, endocrine, and pancreatic disease: A novel nonsense mutation in an Italian family 婴儿期发病的多系统神经系统、内分泌和胰腺疾病的神经系统核心特征:一个意大利家族中的新型无义突变。
IF 3.9 3区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-06-14 DOI: 10.1111/jns.12636
Alessia Mammi, Alessandro Geroldi, Serena Patrone, Fabio Gotta, Paola Origone, Andrea Gaudio, Andrea La Barbera, Francesca Sanguineri, Clarissa Ponti, Michele Iacomino, Monica Traverso, Edoardo Ferlazzo, Angelo Schenone, Angelo Pascarella, Oreste Marsico, Paola Mandich, Emilia Bellone

Aim

Biallelic mutations in the PTRH2 gene have been associated with infantile multisystem neurological, endocrine, and pancreatic disease (IMNEPD), a rare autosomal recessive disorder of variable expressivity characterized by global developmental delay, intellectual disability or borderline IQ level, sensorineural hearing loss, ataxia, and pancreatic insufficiency. Various additional features may be included, such as peripheral neuropathy, facial dysmorphism, hypothyroidism, hepatic fibrosis, postnatal microcephaly, cerebellar atrophy, and epilepsy. Here, we report the first Italian family presenting only predominant neurological features.

Methods

Extensive neurological and neurophysiological evaluations have been conducted on the two affected brothers and their healthy mother since 1996. The diagnosis of peripheral neuropathy of probable hereditary origin was confirmed through a sural nerve biopsy. Exome sequencing was performed after the analysis of major neuropathy-associated genes yielded negative results.

Results

Whole-exome sequencing analysis identified the homozygous substitution c.256C>T (p.Gln86Ter) in the PTRH2 gene in the two siblings. According to American College of Medical Genetics and Genomics (ACMG) guidelines, the variant has been classified as pathogenic.

At 48 years old, the proband's reevaluation confirmed a demyelinating sensorimotor polyneuropathy with bilateral sensorineural hearing loss that had been noted since he was 13. Additionally, drug-resistant epileptic seizures occurred when he was 32 years old. No hepatic or endocrinological signs developed. The younger affected brother, 47 years old, has an overlapping clinical presentation without epilepsy.

Interpretation

Our findings expand the clinical phenotype and further demonstrate the clinical heterogeneity related to PTRH2 variants. We thereby hope to better define IMNEPD and facilitate the identification and diagnosis of this novel disease entity.

目的:PTRH2 基因的双倍突变与婴儿多系统神经病、内分泌病和胰腺病(IMNEPD)有关,IMNEPD 是一种罕见的常染色体隐性遗传疾病,其特征为全身发育迟缓、智力障碍或边缘智商水平、感音神经性听力损失、共济失调和胰腺功能不全。该病还可能伴有各种其他特征,如周围神经病变、面部畸形、甲状腺功能减退、肝纤维化、产后小头畸形、小脑萎缩和癫痫。在此,我们报告了第一个仅表现为主要神经系统特征的意大利家族:方法:自 1996 年以来,我们对患病的两兄弟及其健康的母亲进行了广泛的神经学和神经电生理学评估。通过鞍神经活检,确诊为可能遗传性的周围神经病。在对主要神经病相关基因的分析结果呈阴性后,进行了外显子组测序:结果:全外显子组测序分析发现,这对兄妹的 PTRH2 基因中存在 c.256C>T (p.Gln86Ter) 的同源替换。根据美国医学遗传学和基因组学学院(ACMG)的指南,该变异被归类为致病性。48 岁时,该患者的复查证实,他自 13 岁起就患有脱髓鞘性感觉运动性多发性神经病,并伴有双侧感音神经性听力损失。此外,他在 32 岁时出现了耐药性癫痫发作。没有出现肝脏或内分泌症状。受影响的弟弟现年47岁,其临床表现与他相似,但没有癫痫:我们的研究结果扩展了临床表型,进一步证明了与 PTRH2 变异相关的临床异质性。因此,我们希望能更好地定义 IMNEPD,并促进对这种新型疾病实体的识别和诊断。
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引用次数: 0
期刊
Journal of the Peripheral Nervous System
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