Journal of the Peripheral Nervous System最新文献

{"title":"Two new mouse models of Gjb1-associated Charcot–Marie–Tooth disease type 1X","authors":"A. L. D. Tadenev,&nbsp;C. L. Hatton,&nbsp;B. Pattavina,&nbsp;T. Mullins,&nbsp;R. Schneider,&nbsp;L. P. Bogdanik,&nbsp;Robert W. Burgess","doi":"10.1111/jns.12588","DOIUrl":"10.1111/jns.12588","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Charcot–Marie–Tooth disease type 1X is caused by mutations in <i>GJB1</i>, which is the second most common gene associated with inherited peripheral neuropathy. The <i>GJB1</i> gene encodes connexin 32 (CX32), a gap junction protein expressed in myelinating glial cells. The gene is X-linked, and the mutations cause a loss of function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>A large number of disease-associated variants have been identified, and many result in mistrafficking and mislocalization of the protein. An existing knockout mouse lacking <i>Gjb1</i> expression provides a valid animal model of CMT1X, but the complete lack of protein may not fully recapitulate the disease mechanisms caused by aberrant CX32 proteins. To better represent the spectrum of human CMT1X-associated mutations, we have generated a new <i>Gjb1</i> knockin mouse model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>CRISPR/Cas9 genome editing was used to produce mice carrying the R15Q mutation in <i>Gjb1</i>. In addition, we identified a second allele with an early frame shift mutation in codon 7 (del2). Mice were analyzed using clinically relevant molecular, histological, neurophysiological, and behavioral assays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Both alleles produce protein detectable by immunofluorescence in Schwann cells, with some protein properly localizing to nodes of Ranvier. However, both alleles also result in peripheral neuropathy with thinly myelinated and demyelinated axons, as well as degenerating and regenerating axons, predominantly in distal motor nerves. Nerve conduction velocities were only mildly reduced at later ages and compound muscle action potential amplitudes were not reduced. Levels of neurofilament light chain in plasma were elevated in both alleles. The del2 mice have an onset at ~3 months of age, whereas the R15Q mice had a later onset at 5–6 months of age, suggesting a milder loss of function. Both alleles performed comparably to wild type littermates in accelerating rotarod and grip strength tests of neuromuscular performance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>We have generated and characterized two new mouse models of CMT1X that will be useful for future mechanistic and preclinical studies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"28 3","pages":"317-328"},"PeriodicalIF":3.8,"publicationDate":"2023-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10555766","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":"Benefit of high-dose oral riboflavin therapy in riboflavin transporter deficiency","authors":"Jack R. Fennessy,&nbsp;Kayla M. D. Cornett,&nbsp;Joshua Burns,&nbsp;Manoj P. Menezes","doi":"10.1111/jns.12587","DOIUrl":"10.1111/jns.12587","url":null,"abstract":"<p>Riboflavin transporter deficiency (RTD) is a progressive inherited neuropathy of childhood onset, characterised by pontobulbar palsy, sensorineural deafness, sensory ataxia, muscle weakness, optic atrophy and respiratory failure. Riboflavin supplementation is beneficial in short-term reports, but the quantum of benefit in various clinical domains is not well understood. A PubMed search was conducted, which identified 94 genetically confirmed cases of RTD who received riboflavin supplementation and had follow-up assessments. Information on the clinical and functional status before and after riboflavin supplementation was collected and analysed. Seventy-six of the 94 patients (80.9%) showed an overall improvement after riboflavin supplementation, and the remaining (19.1%) were stable, though some patients had deteriorations in individual domains with no reported deaths. The domains that had the highest rates of response to riboflavin supplementation were gross motor function (93.3% improved), bulbar palsy (91.3%) and ataxia (90.0%). Improvements were also seen in limb muscle weakness, audiology, facial nerve palsy and respiratory function. Despite treatment, many patients required assistance to ambulate and had severe or profound hearing loss and some remained gastrostomy or tracheostomy dependent. Riboflavin supplementation is a lifesaving intervention for patients with RTD and results in a profound improvement in several functional domains, with early diagnosis and treatment further improving outcomes. Despite treatment, patients are left with residual disability. There is a need to accurately measure functional outcomes in children with RTD and develop additional disease-modifying therapies.</p>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"28 3","pages":"308-316"},"PeriodicalIF":3.8,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.12587","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10537716","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}

{"title":"Quantitative sensory testing and skin biopsy findings in late-onset ATTRv presymptomatic carriers: Relationships with predicted time of disease onset (PADO)","authors":"Luca Leonardi,&nbsp;Rocco Costanzo,&nbsp;Francesca Forcina,&nbsp;Stefania Morino,&nbsp;Giovanni Antonini,&nbsp;Marco Salvetti,&nbsp;Marco Luigetti,&nbsp;Angela Romano,&nbsp;Guido Primiano,&nbsp;Valeria Guglielmino,&nbsp;Laura Fionda,&nbsp;Matteo Garibaldi,&nbsp;Antonio Lauletta,&nbsp;Elena Rossini,&nbsp;Laura Tufano,&nbsp;Marco Ceccanti,&nbsp;Nicoletta Esposito,&nbsp;Pietro Falco,&nbsp;Giuseppe di Pietro,&nbsp;Andrea Truini,&nbsp;Eleonora Galosi","doi":"10.1111/jns.12586","DOIUrl":"10.1111/jns.12586","url":null,"abstract":"Hereditary transthyretin amyloidosis polyneuropathy (ATTRv‐PN) presymptomatic carriers often show preclinical abnormalities at small fiber‐related diagnostic tests. However, no validated biomarker is currently available to use for presymptomatic carriers' follow‐up, thus helping therapeutic decision making. Our study aimed at assessing nerve conduction study (NCS), quantitative sensory testing (QST), and skin biopsy parameters in a large cohort of late‐onset ATTRv presymptomatic carriers and to evaluate whether they correlated with predicted age of disease onset (PADO).","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"28 3","pages":"390-397"},"PeriodicalIF":3.8,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.12586","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10183239","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}

{"title":"Differences in the ultrastructure of neurons in the spinal ganglion and dorsal rootlet between rats treated with cisplatin only versus co-administration with a sphingosine 1-phosphate receptor 2 agonist in attenuating neuropathy and allodynia","authors":"Kanokporn Chayaburakul,&nbsp;Wei Yi Ong,&nbsp;Deron R. Herr,&nbsp;Phetnarin Kobutree,&nbsp;Kraisri Chantra","doi":"10.1111/jns.12582","DOIUrl":"10.1111/jns.12582","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Cisplatin is a chemotherapeutic agent for many types of cancer. The neurotoxicity of cisplatin includes neuropathy and allodynia. We aimed to study structural changes by using CYM54-78, attenuating cisplatin-induced neuropathy and blocking the pathogenesis in neurons, and promoting axonal regeneration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>TEM (transmission electron microscopy) was used to distinguish ultrastructural changes in dorsal root ganglion (DRG) and dorsal rootlets (DR) between rats treated with cisplatin alone and rats co-treated with cisplatin and sphingosine -1-phosphate receptor2 (S1P2) agonist, CYM-5478.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In DRG of rats treated with cisplatin alone, TEM micrographs showed necrosis and apoptotic cells. Neuronal cytoplasm showed numerous vacuole (stage C) and swelling (stage B➔C) mitochondrial degeneration. Neurons in DRG from cisplatin+CYM-5478 group showed a higher percentage of healthy mitochondria (from 5.3% to 75.6%) than those treated with cisplatin alone. DR of cisplatin only group showed abnormal axoplasm, axolemma, and focal detached myelin sheaths, especially in Aδ (fast pain) and Aβ (touch) fibers, and revealed collateral branches that sprouted from Aβ fibers, which is characteristic of allodynia. Moreover, vasoconstriction was observed in DRG and DR. Rats in cisplatin+CYM-5478 group showed not only fewer abnormal structures than those in cisplatin only group, but also showed Bands of Büngner and onion bulb-like structures, which are characteristic of nerve regeneration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Together with our previous study, showed that CYM-5478 attenuated neuropathy and allodynia in a rat model of cisplatin-induced neuropathy, these results suggest S1P2 agonists as a potential approach the for treatment of cancer due to the reduction of side effects of cisplatin.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"28 3","pages":"476-489"},"PeriodicalIF":3.8,"publicationDate":"2023-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10186254","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":"Assessing diabetic polyneuropathy in Spanish-speaking patients: Translation and validation of the Toronto Clinical Neuropathy Score","authors":"Juan Francisco Idiáquez Rios,&nbsp;Ignacio Acosta,&nbsp;Alberto Prat,&nbsp;Francesca Gattini,&nbsp;Francisca Pino,&nbsp;Carolina Barnett-Tapia","doi":"10.1111/jns.12577","DOIUrl":"10.1111/jns.12577","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Diabetic sensorimotor polyneuropathy (DSP) is a common complication of diabetes. The Toronto Clinical Neuropathy Score (TCNS) is a useful tool for detecting DSP. However, it is not available in Spanish. The study aimed to translate and culturally adapt the TCNS and modified (mTCNS) scales into Spanish and evaluate their measurement properties.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A multistep forward-backward method was used for translation and cultural adaptation. A panel of physicians subjected the final Spanish versions of TCNS and mTCNS (TCÑS, mTCÑS) to cognitive debriefing. Consecutive patients with diabetes mellitus and DSP were recruited from an outpatient clinic, and the TCÑS and mTCÑS were tested for construct validity, along with other measures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The internal consistency of both TCÑS and mTCÑS was excellent, as evidenced by Cronbach's Alpha coefficients of 0.83 and 0.85, respectively. Furthermore, there was a robust positive correlation between TCÑS and mTCÑS. In addition, TCÑS was found to exhibit a strong negative correlation with sural sensory nerve action potential amplitude (<i>r</i> = −0.9206) and peroneal compound motor action potential amplitude (<i>r</i> = −0.729), while demonstrating a positive and strong correlation with the Michigan Neuropathy Screening Instrument (<i>r</i> = 0.713).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>The TCÑS and mTCÑS are reliable and valid translations of the original TCNS. The TCÑS and mTCÑS can be used to diagnose and measure the severity of neuropathy in Spanish-speaking patients with diabetes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"28 3","pages":"471-475"},"PeriodicalIF":3.8,"publicationDate":"2023-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.12577","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10240899","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}

{"title":"Serum neurofilament light chain measurements following nerve trauma","authors":"Matthew Wilcox,&nbsp;Melissa L. D. Rayner,&nbsp;Owein Guillemot-Legris,&nbsp;Isobel Platt,&nbsp;Hazel Brown,&nbsp;Tom Quick,&nbsp;James B. Phillips","doi":"10.1111/jns.12576","DOIUrl":"10.1111/jns.12576","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Optimal functional recovery following peripheral nerve injuries (PNIs) is dependent upon early recognition and prompt referral to specialist centres for appropriate surgical intervention. Technologies which facilitate the early detection of PNI would allow faster referral rates and encourage improvements in patient outcomes. Serum Neurofilament light chain (NfL) measurements are cheaper to perform, easier to access and interpret than many conventional methods used for nerve injury diagnosis, such as electromyography and/or magnetic resonance imaging assessments, but changes in serum NfL levels following traumatic PNI have not been investigated. This pre-clinical study aimed to determine whether serum NfL levels can: (1) detect the presence of a nerve trauma and (2) delineate between different severities of nerve trauma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A rat sciatic nerve crush and common peroneal nerve crush were implemented as controlled animal models of nerve injury. At 1-, 3-, 7- and 21-days post-injury, serum samples were retrieved for analysis using the SIMOA® NfL analyser kit. Nerve samples were also retrieved for histological analysis. Static sciatic index (SSI) was measured at regular time intervals following injury.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Significant 45-fold and 20-fold increases in NfL serum levels were seen 1-day post-injury following sciatic and common peroneal nerve injury, respectively. This corresponded with an eightfold higher volume of axons injured in the sciatic compared to the common peroneal nerve (<i>p</i> &lt; .001). SSI measurements post-injury revealed greater reduction in function in the sciatic crush group compared with the common peroneal crush group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>NfL serum measurements represent a promising method for detecting traumatic PNI and stratifying their severity. Clinical translation of these findings could provide a powerful tool to improve the surgical management of nerve-injured patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"28 3","pages":"500-507"},"PeriodicalIF":3.8,"publicationDate":"2023-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.12576","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10555338","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}

{"title":"Plasma neurofilament light chain concentrations are elevated in youth-onset type 2 diabetes and associated with neuropathy","authors":"Vera Fridman,&nbsp;Stefan Sillau,&nbsp;Alanna Ritchie,&nbsp;Jacob Bockhorst,&nbsp;Christina Coughlan,&nbsp;Paula Araya,&nbsp;Joaquin M. Espinosa,&nbsp;Keith Smith,&nbsp;Ethan M. Lange,&nbsp;Leslie A. Lange,&nbsp;Laure El Ghormli,&nbsp;Kimberly L. Drews,&nbsp;Philip Zeitler,&nbsp;Jane E. B. Reusch","doi":"10.1111/jns.12575","DOIUrl":"10.1111/jns.12575","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>The lack of easily measurable biomarkers remains a challenge in executing clinical trials for diabetic neuropathy (DN). Plasma Neurofilament light chain (NFL) concentration is a promising biomarker in immune-mediated neuropathies. Longitudinal studies evaluating NFL in DN have not been performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A nested case–control study was performed on participants with youth-onset type 2 diabetes enrolled in the prospective Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. Plasma NFL concentrations were measured at 4-year intervals from 2008 to 2020 in 50 participants who developed DN and 50 participants with type 2 diabetes who did not develop DN.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>NFL concentrations were similar in the DN and no DN groups at the first assessment. Concentrations were higher in DN participants at all subsequent assessment periods (all <i>p</i> &lt; .01). NFL concentrations increased over time in both groups, with higher degrees of change in DN participants (interaction <i>p</i> = .045). A doubling of the NFL value at Assessment 2 in those without DN increased the odds of ultimate DN outcome by an estimated ratio of 2.86 (95% CI: [1.30, 6.33], <i>p</i> = .0046). At the final study visit, positive Spearman correlations (controlled for age, sex, diabetes duration, and BMI) were observed between NFL and HbA1c (0.48, <i>p</i> &lt; .0001), total cholesterol (0.25, <i>p</i> = .018), and low-density lipoprotein (LDL (0.30, <i>p</i> = .0037)). Negative correlations were observed with measures of heart rate variability (−0.42 to −0.46, <i>p</i> = &lt;.0001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>The findings that NFL concentrations are elevated in individuals with youth-onset type 2 diabetes, and increase more rapidly in those who develop DN, suggest that NFL could be a valuable biomarker for DN.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"28 3","pages":"460-470"},"PeriodicalIF":3.8,"publicationDate":"2023-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.12575","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10627947","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}

{"title":"Hyaluronidase-facilitated subcutaneous immunoglobulin 10% as maintenance therapy for chronic inflammatory demyelinating polyradiculoneuropathy: The ADVANCE-CIDP 1 randomized controlled trial","authors":"Vera Bril,&nbsp;Robert D. M. Hadden,&nbsp;Thomas H. Brannagan III,&nbsp;Michal Bar,&nbsp;Elisabeth Chroni,&nbsp;Konrad Rejdak,&nbsp;Alberto Rivero,&nbsp;Henning Andersen,&nbsp;Norman Latov,&nbsp;Todd Levine,&nbsp;Mamatha Pasnoor,&nbsp;Sabrina Sacconi,&nbsp;Nizar Souayah,&nbsp;Colin Anderson-Smits,&nbsp;Kim Duff,&nbsp;Erin Greco,&nbsp;Shabbir Hasan,&nbsp;Zhaoyang Li,&nbsp;Leman Yel,&nbsp;Hakan Ay","doi":"10.1111/jns.12573","DOIUrl":"10.1111/jns.12573","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>ADVANCE-CIDP 1 evaluated facilitated subcutaneous immunoglobulin (fSCIG; human immunoglobulin G 10% with recombinant human hyaluronidase) efficacy and safety in preventing chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) relapse.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>ADVANCE-CIDP 1 was a phase 3, double-blind, placebo-controlled trial conducted at 54 sites in 21 countries. Eligible adults had definite or probable CIDP and adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability scores of 0–7 (inclusive), and received stable intravenous immunoglobulin (IVIG) for ≥12 weeks before screening. After stopping IVIG, patients were randomized 1:1 to fSCIG 10% or placebo for 6 months or until relapse/discontinuation. fSCIG 10% was administered at the same dose (or matching placebo volume) and interval as pre-randomization IVIG. The primary outcome was patient proportion experiencing CIDP relapse (≥1-point increase in adjusted INCAT score from pre-subcutaneous treatment baseline) in the modified intention-to-treat population. Secondary outcomes included time to relapse and safety endpoints.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Overall, 132 patients (mean age 54.4 years, 56.1% male) received fSCIG 10% (<i>n</i> = 62) or placebo (<i>n</i> = 70). CIDP relapse was reduced with fSCIG 10% versus placebo (<i>n</i> = 6 [9.7%; 95% confidence interval 4.5%, 19.6%] vs <i>n</i> = 22 [31.4%; 21.8%, 43.0%], respectively; absolute difference: −21.8% [−34.5%, −7.9%], <i>p</i> = .0045). Relapse probability was higher with placebo versus fSCIG 10% over time (<i>p</i> = .002). Adverse events (AEs) were more frequent with fSCIG 10% (79.0% of patients) than placebo (57.1%), but severe (1.6% vs 8.6%) and serious AEs (3.2% vs 7.1%) were less common.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>fSCIG 10% more effectively prevented CIDP relapse than placebo, supporting its potential use as maintenance CIDP treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"28 3","pages":"436-449"},"PeriodicalIF":3.8,"publicationDate":"2023-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.12573","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10555328","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}

{"title":"EGR2 gene-linked hereditary neuropathies present with a bimodal age distribution at symptoms onset","authors":"Andoni Echaniz-Laguna,&nbsp;Cécile Cauquil,&nbsp;Jean-Baptiste Chanson,&nbsp;Céline Tard,&nbsp;Lucie Guyant-Marechal,&nbsp;Thierry Kuntzer,&nbsp;Ioana Maria Ion,&nbsp;Anne-Sophie Lia,&nbsp;Jérôme Bouligand,&nbsp;Vianney Poinsignon","doi":"10.1111/jns.12572","DOIUrl":"10.1111/jns.12572","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Mutations in the <i>Early-Growth Response 2</i> (<i>EGR2</i>) gene cause various hereditary neuropathies, including demyelinating Charcot–Marie-Tooth (CMT) disease type 1D (CMT1D), congenital hypomyelinating neuropathy type 1 (CHN1), Déjerine–Sottas syndrome (DSS), and axonal CMT (CMT2).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, we identified 14 patients with heterozygous <i>EGR2</i> mutations diagnosed between 2000 and 2022.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Mean age was 44 years (15–70), 10 patients were female (71%), and mean disease duration was 28 years (1–56). Disease onset was before age 15 years in nine cases (64%), after age 35 years in four cases (28%), and one patient aged 26 years was asymptomatic (7%). All symptomatic patients had <i>pes cavus</i> and distal lower limbs weakness (100%). Distal lower limbs sensory symptoms were observed in 86% of cases, hand atrophy in 71%, and scoliosis in 21%. Nerve conduction studies showed a predominantly demyelinating sensorimotor neuropathy in all cases (100%), and five patients needed walking assistance after a mean disease duration of 50 years (47–56) (36%). Three patients were misdiagnosed as inflammatory neuropathy and treated with immunosuppressive drugs for years before diagnosis was corrected. Two patients presented with an additional neurologic disorder, including Steinert's myotonic dystrophy and spinocerebellar ataxia (14%). Eight <i>EGR2</i> gene mutations were found, including four previously undescribed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation.</h3>\u0000 \u0000 <p>Our findings demonstrate <i>EGR2</i> gene-related hereditary neuropathies are rare and slowly progressive demyelinating neuropathies with two major clinical presentations, including a childhood-onset variant and an adult-onset variant which may mimic inflammatory neuropathy. Our study also expands the genotypic spectrum of <i>EGR2</i> gene mutations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"28 3","pages":"359-367"},"PeriodicalIF":3.8,"publicationDate":"2023-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10182562","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":"Nodes of Ranvier in health and disease","authors":"Yael Eshed-Eisenbach,&nbsp;Peter J. Brophy,&nbsp;Elior Peles","doi":"10.1111/jns.12568","DOIUrl":"10.1111/jns.12568","url":null,"abstract":"<p>Action potential propagation along myelinated axons depends on the geometry of the myelin unit and the division of the underlying axon to specialized domains. The latter include the nodes of Ranvier (NOR), the paranodal junction (PNJ) flanking the nodes, and the adjacent juxtaparanodal region that is located below the compact myelin of the internode. Each of these domains contains a unique composition of axoglial adhesion molecules (CAMs) and cytoskeletal scaffolding proteins, which together direct the placement of specific ion channels at the nodal and juxtaparanodal axolemma. In the last decade it has become increasingly clear that antibodies to some of these axoglial CAMs cause immune-mediated neuropathies. In the current review we detail the molecular composition of the NOR and adjacent membrane domains, describe the function of different CAM complexes that mediate axon-glia interactions along the myelin unit, and discuss their involvement and the underlying mechanisms taking place in peripheral nerve pathologies. This growing group of pathologies represent a new type of neuropathies termed “nodopathies” or “paranodopathies” that are characterized by unique clinical and molecular features which together reflect the mechanisms underlying the molecular assembly and maintenance of this specialized membrane domain.</p>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"28 S3","pages":"S3-S11"},"PeriodicalIF":3.8,"publicationDate":"2023-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.12568","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9834540","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}