Vanessa Daccach, Pedro José Tomaselli, Juliana Secchin Algemiro, Patricia Toscano, André Cleriston José dos Santos, Marco Andrey Cipriano Frade, Wilson Marques Jr.
Background and Aims
Leprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae), an intracellular bacillus that systematically invades the peripheral nerves. Diagnosing leprosy neuropathy is still a defying skill, and late diagnosis and treatment are still a reality. Based on the biological characteristics of M. leprae, particularly its preference for invading the Schwann cells localized at the coldest areas of human body, we hypothesized that these areas have focal demyelination that may escape detection through standard nerve conduction studies (NCSs) protocols.
Methods
Twenty-five patients with confirmed multibacillary leprosy and 14 controls were accessed. A multisegmented NCS protocol (MP) was performed, targeting short segments through the coldest areas, to identify focal areas of slowed conduction velocity. The effectiveness of this multisegmented protocol was compared to the standard protocol (SP) to detect abnormalities.
Results
All leprosy patients presented an abnormal study with the MP, contrasting to 19 with the SP. The most frequent NCS pattern was an asymmetric neuropathy with focal slowing of conduction velocity, found in 23 out of 25 leprosy patients. Significant differences favoring the proposed method were observed when comparing the MP with the SP. Notably, the MP increased the sensitivity to detect abnormalities by 122%, 133%, and 257% for the median, peroneal, and tibial nerves, respectively. MP also increases sensitivity to detect focal abnormalities in the ulnar nerve.
Interpretation
The MP protocol significantly increases the sensitivity of NCSs to detect neurophysiological abnormalities in leprosy neuropathy.
{"title":"Focal slowing of nerve conduction velocity in leprosy patients unveiled through multisegmented nerve analysis","authors":"Vanessa Daccach, Pedro José Tomaselli, Juliana Secchin Algemiro, Patricia Toscano, André Cleriston José dos Santos, Marco Andrey Cipriano Frade, Wilson Marques Jr.","doi":"10.1111/jns.12649","DOIUrl":"10.1111/jns.12649","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Leprosy is a chronic infectious disease caused by <i>Mycobacterium leprae</i> (<i>M. leprae</i>), an intracellular bacillus that systematically invades the peripheral nerves. Diagnosing leprosy neuropathy is still a defying skill, and late diagnosis and treatment are still a reality. Based on the biological characteristics of <i>M. leprae,</i> particularly its preference for invading the Schwann cells localized at the coldest areas of human body, we hypothesized that these areas have focal demyelination that may escape detection through standard nerve conduction studies (NCSs) protocols.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Twenty-five patients with confirmed multibacillary leprosy and 14 controls were accessed. A multisegmented NCS protocol (MP) was performed, targeting short segments through the coldest areas, to identify focal areas of slowed conduction velocity. The effectiveness of this multisegmented protocol was compared to the standard protocol (SP) to detect abnormalities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>All leprosy patients presented an abnormal study with the MP, contrasting to 19 with the SP. The most frequent NCS pattern was an asymmetric neuropathy with focal slowing of conduction velocity, found in 23 out of 25 leprosy patients. Significant differences favoring the proposed method were observed when comparing the MP with the SP. Notably, the MP increased the sensitivity to detect abnormalities by 122%, 133%, and 257% for the median, peroneal, and tibial nerves, respectively. MP also increases sensitivity to detect focal abnormalities in the ulnar nerve.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>The MP protocol significantly increases the sensitivity of NCSs to detect neurophysiological abnormalities in leprosy neuropathy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"29 3","pages":"356-362"},"PeriodicalIF":3.9,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008981","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}
{"title":"PNS Abstracts 2024","authors":"","doi":"10.1111/jns.12648","DOIUrl":"10.1111/jns.12648","url":null,"abstract":"","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"29 S3","pages":"S3-S193"},"PeriodicalIF":3.9,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008982","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}
Yongsheng Zheng, Chong Sun, Yanyin Zhao, Quanhua Meng, Jianian Hu, Kai Qiao, Jian Sun, Jianying Xi, Sushan Luo, Jiahong Lu, Chongbo Zhao, Jie Lin
Objective
To evaluate the efficacy and safety of a low-dose, long-term rituximab regimen in the treatment of idiopathic CIDP.
Methods
This study included 15 CIDP patients treated with rituximab. Patients were administered 600 mg of rituximab intravenously every 6 months. Baseline evaluation was conducted before the initiation of rituximab treatment and subsequent evaluations were conducted 6 months after each rituximab infusion at on-site visits. Clinical improvement was objectively determined by improvement of scale score at least decrease ≥1 INCAT or mRS or increase ≥4 MRC or ≥8 cI-RODS after each infusion compared to baseline evaluation.
Results
Fifteen CIDP patients were included and 10 of them were typical CIDP and five were distal CIDP. Nine in 15 (60%) patients after first infusion and three in six (50%) patients after second infusion exhibited significant clinical improvement compared to baseline evaluation. Additionally, rituximab facilitated a reduction or cessation of other medications in 73% of patients at last visit. The safety profile was favorable, with no reported adverse events.
Conclusion
Rituximab presents a promising therapeutic option for idiopathic CIDP, offering both efficacy and safety with a low-dose, long-term regimen.
{"title":"Long-term and low-dose rituximab treatment for chronic inflammatory demyelinating polyneuropathy","authors":"Yongsheng Zheng, Chong Sun, Yanyin Zhao, Quanhua Meng, Jianian Hu, Kai Qiao, Jian Sun, Jianying Xi, Sushan Luo, Jiahong Lu, Chongbo Zhao, Jie Lin","doi":"10.1111/jns.12653","DOIUrl":"10.1111/jns.12653","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To evaluate the efficacy and safety of a low-dose, long-term rituximab regimen in the treatment of idiopathic CIDP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study included 15 CIDP patients treated with rituximab. Patients were administered 600 mg of rituximab intravenously every 6 months. Baseline evaluation was conducted before the initiation of rituximab treatment and subsequent evaluations were conducted 6 months after each rituximab infusion at on-site visits. Clinical improvement was objectively determined by improvement of scale score at least decrease ≥1 INCAT or mRS or increase ≥4 MRC or ≥8 cI-RODS after each infusion compared to baseline evaluation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fifteen CIDP patients were included and 10 of them were typical CIDP and five were distal CIDP. Nine in 15 (60%) patients after first infusion and three in six (50%) patients after second infusion exhibited significant clinical improvement compared to baseline evaluation. Additionally, rituximab facilitated a reduction or cessation of other medications in 73% of patients at last visit. The safety profile was favorable, with no reported adverse events.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Rituximab presents a promising therapeutic option for idiopathic CIDP, offering both efficacy and safety with a low-dose, long-term regimen.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"29 3","pages":"350-355"},"PeriodicalIF":3.9,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995972","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}
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。
{"title":"Correction to “Earlier diagnosis of peripheral neuropathy in primary care: A call to action”","authors":"","doi":"10.1111/jns.12652","DOIUrl":"10.1111/jns.12652","url":null,"abstract":"<p>Gad H, Kalra S, Pinzon R, et al. Earlier diagnosis of peripheral neuropathy in primary care: a call to action. <i>J Peripher Nerv Syst</i>. 2024;29(1):28-37. doi:10.1111/jns.12613</p><p>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.</p><p>We apologize for this error.</p>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"29 3","pages":"378"},"PeriodicalIF":3.9,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.12652","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982599","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}
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.
{"title":"Diagnostic and clinical utility of comprehensive multigene panel testing for patients with neuropathy","authors":"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","doi":"10.1111/jns.12651","DOIUrl":"10.1111/jns.12651","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>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 <i>PMP22</i>, <i>MFN2</i>, <i>GJB1</i>, and <i>MPZ</i> 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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A molecular diagnosis was identified for 8.4% of the cohort (<i>n</i> = 573/6849). Variants in <i>PMP22</i>, <i>MFN2</i>, <i>GJB1</i>, <i>MPZ</i>, and <i>TTR</i> 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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"29 3","pages":"363-367"},"PeriodicalIF":3.9,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.12651","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976021","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}
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.
{"title":"Initial findings using high-resolution magnetic resonance imaging for visualisation of the sural nerve and surrounding anatomy in healthy volunteers at 7 Tesla","authors":"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","doi":"10.1111/jns.12645","DOIUrl":"10.1111/jns.12645","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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 mm<sup>2</sup>, diameter and location relative to nearby vessels and muscles).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"29 3","pages":"368-375"},"PeriodicalIF":3.9,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.12645","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759521","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}
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.
{"title":"Correction to ‘Serum neurofilament light chain measurements following nerve trauma’","authors":"","doi":"10.1111/jns.12642","DOIUrl":"10.1111/jns.12642","url":null,"abstract":"<p>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</p><p>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%’.</p><p>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.</p><p>We apologise for this error.</p>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"29 3","pages":"376-377"},"PeriodicalIF":3.9,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.12642","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590639","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}
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.
{"title":"Efficacy and safety of eculizumab in Guillain-Barré syndrome: A phase 3, multicenter, double-blind, randomized, placebo-controlled clinical trial","authors":"Satoshi Kuwabara, Susumu Kusunoki, Motoi Kuwahara, Yoshihisa Yamano, Yoichiro Nishida, Hirokazu Ishida, Tomoyuki Kasuya, Erik Kupperman, Qun Lin, Glen Frick, 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":"29 3","pages":"339-349"},"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}
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.
{"title":"Clinical, histologic, and immunologic signatures of Small Fiber Neuropathy in Systemic Lupus Erythematosus","authors":"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","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":"29 3","pages":"315-328"},"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}
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.
{"title":"Identification of cellular and noncellular components of mature intact human peripheral nerve","authors":"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","doi":"10.1111/jns.12643","DOIUrl":"10.1111/jns.12643","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>The goal of this study was to define basic constituents of the adult peripheral nervous system (PNS) using intact human nerve tissues.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Our optimized methods revealed additional detailed information to update our understanding of the complexity and spatial orientation of PNS-resident cell types in humans.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"29 3","pages":"294-314"},"PeriodicalIF":3.9,"publicationDate":"2024-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555047","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}
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