Arman Çakar, Gulandam Bagırova, Hacer Durmuş, Oya Uyguner, Yeşim Parman
Background and Aims
Homozygous loss-of-function mutations in the RETREG1 gene result in Hereditary Sensory Autonomic Neuropathy Type 2B. Clinical features include pain loss, autonomic disturbances, and upper motor neuron features.
Methods
We evaluated the clinical and genetic features of seven patients from four families with RETREG1 variants.
Results
Five patients were male. The median age of disease onset was 7.00 ± 2.81 (between 2 and 10 years). A combination of painless wounds, trophic changes, and foot ulcerations was the presenting symptom in five patients and walking difficulties in two. Motor symptoms were present in five patients. In a median disease duration of 30.00 ± 12.88 years, five patients had osteomyelitis, and three had toe amputations. A history of renal disease was present in one family. In another family, three affected siblings had short stature and a history of delayed puberty. Although sensory signs predominated the clinical findings, various degrees of motor signs such as muscle weakness, spasticity, and brisk tendon reflexes were noted in all patients. Nerve conduction studies showed axonal sensory-motor neuropathy in five patients and sensory neuropathy in two. Three pathogenic variants were identified in the RETREG1 gene. Two unrelated patients had a homozygous c.433C > T/p.(Gln145*), one a homozygous c.826delA/p.(Ser276Valfs*8), and the last had a novel homozygous c.102delC/p.(Ala35Glnfs*349) variants.
Interpretation
In our study, all patients showed signs and symptoms consistent with pain insensitivity. Although shadowed by sensory symptoms, motor signs were noted in our patients. Further studies are necessary to clarify the causal relationship between extra-neurological features and RETREG1 mutations.
{"title":"Phenotypic features of RETREG1-related hereditary sensory autonomic neuropathy","authors":"Arman Çakar, Gulandam Bagırova, Hacer Durmuş, Oya Uyguner, Yeşim Parman","doi":"10.1111/jns.12581","DOIUrl":"10.1111/jns.12581","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Homozygous loss-of-function mutations in the <i>RETREG1</i> gene result in Hereditary Sensory Autonomic Neuropathy Type 2B. Clinical features include pain loss, autonomic disturbances, and upper motor neuron features.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We evaluated the clinical and genetic features of seven patients from four families with <i>RETREG1</i> variants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Five patients were male. The median age of disease onset was 7.00 ± 2.81 (between 2 and 10 years). A combination of painless wounds, trophic changes, and foot ulcerations was the presenting symptom in five patients and walking difficulties in two. Motor symptoms were present in five patients. In a median disease duration of 30.00 ± 12.88 years, five patients had osteomyelitis, and three had toe amputations. A history of renal disease was present in one family. In another family, three affected siblings had short stature and a history of delayed puberty. Although sensory signs predominated the clinical findings, various degrees of motor signs such as muscle weakness, spasticity, and brisk tendon reflexes were noted in all patients. Nerve conduction studies showed axonal sensory-motor neuropathy in five patients and sensory neuropathy in two. Three pathogenic variants were identified in the <i>RETREG1</i> gene. Two unrelated patients had a homozygous c.433C > T/p.(Gln145*), one a homozygous c.826delA/p.(Ser276Valfs*8), and the last had a novel homozygous c.102delC/p.(Ala35Glnfs*349) variants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>In our study, all patients showed signs and symptoms consistent with pain insensitivity. Although shadowed by sensory symptoms, motor signs were noted in our patients. Further studies are necessary to clarify the causal relationship between extra-neurological features and RETREG1 mutations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"28 3","pages":"351-358"},"PeriodicalIF":3.8,"publicationDate":"2023-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10187773","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}
Aurore Fernandez, Guillaume Graf, Aurélie Lasserre, Jean-Bernard Daeppen, Paul Chu Sin Chung, Chantal Berna, Marc R. Suter
Introduction
Chronic heavy alcohol use is known to cause neurological complications such as peripheral neuropathy. Concerning the pathophysiology, few sural nerve and skin biopsy studies showed that small fibers might be selectively vulnerable to degeneration in alcohol-related peripheral neuropathy. Pain has rarely been properly evaluated in this pathology. The present study aims at assessing pain intensity, potential neuropathic characteristics as well as the functionality of both small and large nerve sensitive fibers.
Methods
In this observational study, 27 consecutive adult patients, hospitalized for alcohol withdrawal and 13 healthy controls were recruited. All the participants underwent a quantitative sensory testing (QST) according to the standardized protocol of the German Research Network Neuropathic Pain, a neurological examination and filled standardized questionnaires assessing alcohol consumption and dependence as well as pain characteristics and psychological comorbidities.
Results
Nearly half of the patients (13/27) reported pain. Yet, pain intensity was weak, leading to a low interference with daily life, and its characteristics did not support a neuropathic component. A functional impairment of small nerve fibers was frequently described, with thermal hypoesthesia observed in 52% of patients. Patients with a higher alcohol consumption over the last 2 years showed a greater impairment of small fiber function.
Discussion
Patients report pain but it is however unlikely to be caused by peripheral neuropathy given the non-length-dependent distribution and the absence of neuropathic pain features. Chronic pain in AUD deserves to be better evaluated and managed as it represents an opportunity to improve long-term clinical outcomes, potentially participating to relapse prevention.
{"title":"Somatosensory profiling of patients undergoing alcohol withdrawal: Do neuropathic pain and sensory loss represent a problem?","authors":"Aurore Fernandez, Guillaume Graf, Aurélie Lasserre, Jean-Bernard Daeppen, Paul Chu Sin Chung, Chantal Berna, Marc R. Suter","doi":"10.1111/jns.12578","DOIUrl":"10.1111/jns.12578","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Chronic heavy alcohol use is known to cause neurological complications such as peripheral neuropathy. Concerning the pathophysiology, few sural nerve and skin biopsy studies showed that small fibers might be selectively vulnerable to degeneration in alcohol-related peripheral neuropathy. Pain has rarely been properly evaluated in this pathology. The present study aims at assessing pain intensity, potential neuropathic characteristics as well as the functionality of both small and large nerve sensitive fibers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this observational study, 27 consecutive adult patients, hospitalized for alcohol withdrawal and 13 healthy controls were recruited. All the participants underwent a quantitative sensory testing (QST) according to the standardized protocol of the German Research Network Neuropathic Pain, a neurological examination and filled standardized questionnaires assessing alcohol consumption and dependence as well as pain characteristics and psychological comorbidities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Nearly half of the patients (13/27) reported pain. Yet, pain intensity was weak, leading to a low interference with daily life, and its characteristics did not support a neuropathic component. A functional impairment of small nerve fibers was frequently described, with thermal hypoesthesia observed in 52% of patients. Patients with a higher alcohol consumption over the last 2 years showed a greater impairment of small fiber function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Patients report pain but it is however unlikely to be caused by peripheral neuropathy given the non-length-dependent distribution and the absence of neuropathic pain features. Chronic pain in AUD deserves to be better evaluated and managed as it represents an opportunity to improve long-term clinical outcomes, potentially participating to relapse prevention.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"28 3","pages":"490-499"},"PeriodicalIF":3.8,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.12578","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10187761","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}
Juan Francisco Idiáquez Rios, Ignacio Acosta, Alberto Prat, Francesca Gattini, Francisca Pino, Carolina Barnett-Tapia
Background and Aims
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.
Methods
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.
Results
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 (r = −0.9206) and peroneal compound motor action potential amplitude (r = −0.729), while demonstrating a positive and strong correlation with the Michigan Neuropathy Screening Instrument (r = 0.713).
Interpretation
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.
{"title":"Assessing diabetic polyneuropathy in Spanish-speaking patients: Translation and validation of the Toronto Clinical Neuropathy Score","authors":"Juan Francisco Idiáquez Rios, Ignacio Acosta, Alberto Prat, Francesca Gattini, Francisca Pino, 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}
Matthew Wilcox, Melissa L. D. Rayner, Owein Guillemot-Legris, Isobel Platt, Hazel Brown, Tom Quick, James B. Phillips
Background
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.
Methods
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.
Results
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 (p < .001). SSI measurements post-injury revealed greater reduction in function in the sciatic crush group compared with the common peroneal crush group.
Conclusions
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.
{"title":"Serum neurofilament light chain measurements following nerve trauma","authors":"Matthew Wilcox, Melissa L. D. Rayner, Owein Guillemot-Legris, Isobel Platt, Hazel Brown, Tom Quick, 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> < .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}
Vera Fridman, Stefan Sillau, Alanna Ritchie, Jacob Bockhorst, Christina Coughlan, Paula Araya, Joaquin M. Espinosa, Keith Smith, Ethan M. Lange, Leslie A. Lange, Laure El Ghormli, Kimberly L. Drews, Philip Zeitler, Jane E. B. Reusch
Background and Aims
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.
Methods
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.
Results
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 p < .01). NFL concentrations increased over time in both groups, with higher degrees of change in DN participants (interaction p = .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], p = .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, p < .0001), total cholesterol (0.25, p = .018), and low-density lipoprotein (LDL (0.30, p = .0037)). Negative correlations were observed with measures of heart rate variability (−0.42 to −0.46, p = <.0001).
Interpretation
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.
{"title":"Plasma neurofilament light chain concentrations are elevated in youth-onset type 2 diabetes and associated with neuropathy","authors":"Vera Fridman, Stefan Sillau, Alanna Ritchie, Jacob Bockhorst, Christina Coughlan, Paula Araya, Joaquin M. Espinosa, Keith Smith, Ethan M. Lange, Leslie A. Lange, Laure El Ghormli, Kimberly L. Drews, Philip Zeitler, 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> < .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> < .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> = <.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}
Vera Bril, Robert D. M. Hadden, Thomas H. Brannagan III, Michal Bar, Elisabeth Chroni, Konrad Rejdak, Alberto Rivero, Henning Andersen, Norman Latov, Todd Levine, Mamatha Pasnoor, Sabrina Sacconi, Nizar Souayah, Colin Anderson-Smits, Kim Duff, Erin Greco, Shabbir Hasan, Zhaoyang Li, Leman Yel, Hakan Ay
Background and Aims
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.
Methods
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.
Results
Overall, 132 patients (mean age 54.4 years, 56.1% male) received fSCIG 10% (n = 62) or placebo (n = 70). CIDP relapse was reduced with fSCIG 10% versus placebo (n = 6 [9.7%; 95% confidence interval 4.5%, 19.6%] vs n = 22 [31.4%; 21.8%, 43.0%], respectively; absolute difference: −21.8% [−34.5%, −7.9%], p = .0045). Relapse probability was higher with placebo versus fSCIG 10% over time (p = .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.
Interpretation
fSCIG 10% more effectively prevented CIDP relapse than placebo, supporting its potential use as maintenance CIDP treatment.
背景与目的ADVANCE-CIDP 1评估促性皮下免疫球蛋白(fSCIG;人免疫球蛋白G 10%联合重组人透明质酸酶预防慢性炎症性脱髓鞘性多根神经病变(CIDP)复发的有效性和安全性。ADVANCE-CIDP 1是一项3期、双盲、安慰剂对照试验，在21个国家的54个地点进行。符合条件的成年人有明确或可能的CIDP，调整炎症性神经病变病因和治疗(INCAT)残疾评分为0-7分(含)，并在筛查前接受稳定静脉注射免疫球蛋白(IVIG)≥12周。停止IVIG后，患者按1:1随机分配至fSCIG 10%或安慰剂组，持续6个月或直到复发/停药。10%的fSCIG以与预随机IVIG相同的剂量(或匹配的安慰剂体积)和间隔给予。主要结局是在修改意向治疗人群中经历CIDP复发的患者比例(与皮下治疗前基线相比，调整后的INCAT评分增加≥1分)。次要终点包括复发时间和安全性终点。结果132例患者(平均年龄54.4岁，56.1%为男性)接受fSCIG 10% (n = 62)或安慰剂(n = 70)治疗。与安慰剂相比，fSCIG组CIDP复发率降低10% (n = 6 [9.7%;95%置信区间4.5%，19.6%]vs n = 22 [31.4%;21.8%， 43.0%];绝对的区别:−−−34.5%,7.9%,21.8% p = .0045)。随着时间的推移，安慰剂组的复发概率比fSCIG组高10% (p = 0.002)。fSCIG组不良事件(ae)发生率为10%(79.0%)高于安慰剂组(57.1%)，但严重(1.6% vs 8.6%)和严重(3.2% vs 7.1%)不良事件发生率较低。解释fSCIG预防CIDP复发的效果比安慰剂高10%，支持其作为维持CIDP治疗的潜力。
{"title":"Hyaluronidase-facilitated subcutaneous immunoglobulin 10% as maintenance therapy for chronic inflammatory demyelinating polyradiculoneuropathy: The ADVANCE-CIDP 1 randomized controlled trial","authors":"Vera Bril, Robert D. M. Hadden, Thomas H. Brannagan III, Michal Bar, Elisabeth Chroni, Konrad Rejdak, Alberto Rivero, Henning Andersen, Norman Latov, Todd Levine, Mamatha Pasnoor, Sabrina Sacconi, Nizar Souayah, Colin Anderson-Smits, Kim Duff, Erin Greco, Shabbir Hasan, Zhaoyang Li, Leman Yel, 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}
Matthew Silsby, Con Yiannikas, Alessandro F. Fois, Karl Ng, Matthew C. Kiernan, Victor S. C. Fung, Steve Vucic
Background and Aims
Imbalance is a prominent symptom of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Although upper limb tremor in CIDP is described, lower limb tremor has not been assessed. The aim of this study was to determine whether lower limb tremor was present in CIDP and assess potential relationships with imbalance.
Methods
This was a cross-sectional observational study of prospectively recruited consecutive patients with typical CIDP (N = 25). Clinical phenotyping, lower limb nerve conduction and tremor studies, and posturography analyses were performed. The Berg Balance Scale (BBS) divided CIDP patients into those with “good” and “poor” balance.
Results
Lower limb tremor was evident in 32% of CIDP patients and associated with poor balance (BBSTremor 35 [23–46], BBSNo Tremor 52 [44–55], p = .035). Tremor frequency was 10.2–12.5 Hz with legs outstretched and on standing, apart from four patients with a lower frequency tremor (3.8–4.6 Hz) while standing. Posturography analysis revealed a high-frequency spectral peak in the vertical axis in 44% of CIDP patients (16.0 ± 0.4 Hz). This was more likely in those with “good” balance (40% vs. 4%, p = .013).
Interpretation
Lower limb tremor is present in one third of CIDP patients and is associated with poor balance. A high-frequency peak on posturography is associated with better balance in CIDP. Lower limb tremor and posturography assessments could serve as important biomarkers of balance in a clinical setting.
{"title":"Imbalance and lower limb tremor in chronic inflammatory demyelinating polyradiculoneuropathy","authors":"Matthew Silsby, Con Yiannikas, Alessandro F. Fois, Karl Ng, Matthew C. Kiernan, Victor S. C. Fung, Steve Vucic","doi":"10.1111/jns.12574","DOIUrl":"10.1111/jns.12574","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Imbalance is a prominent symptom of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Although upper limb tremor in CIDP is described, lower limb tremor has not been assessed. The aim of this study was to determine whether lower limb tremor was present in CIDP and assess potential relationships with imbalance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This was a cross-sectional observational study of prospectively recruited consecutive patients with typical CIDP (<i>N</i> = 25). Clinical phenotyping, lower limb nerve conduction and tremor studies, and posturography analyses were performed. The Berg Balance Scale (BBS) divided CIDP patients into those with “good” and “poor” balance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Lower limb tremor was evident in 32% of CIDP patients and associated with poor balance (BBS<sub>Tremor</sub> 35 [23–46], BBS<sub>No Tremor</sub> 52 [44–55], <i>p</i> = .035). Tremor frequency was 10.2–12.5 Hz with legs outstretched and on standing, apart from four patients with a lower frequency tremor (3.8–4.6 Hz) while standing. Posturography analysis revealed a high-frequency spectral peak in the vertical axis in 44% of CIDP patients (16.0 ± 0.4 Hz). This was more likely in those with “good” balance (40% vs. 4%, <i>p</i> = .013).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Lower limb tremor is present in one third of CIDP patients and is associated with poor balance. A high-frequency peak on posturography is associated with better balance in CIDP. Lower limb tremor and posturography assessments could serve as important biomarkers of balance in a clinical setting.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"28 3","pages":"415-424"},"PeriodicalIF":3.8,"publicationDate":"2023-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.12574","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10184231","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}
Mutations in the Early-Growth Response 2 (EGR2) 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).
Methods
In this study, we identified 14 patients with heterozygous EGR2 mutations diagnosed between 2000 and 2022.
Results
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 pes cavus 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 EGR2 gene mutations were found, including four previously undescribed.
Interpretation.
Our findings demonstrate EGR2 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 EGR2 gene mutations.
{"title":"EGR2 gene-linked hereditary neuropathies present with a bimodal age distribution at symptoms onset","authors":"Andoni Echaniz-Laguna, Cécile Cauquil, Jean-Baptiste Chanson, Céline Tard, Lucie Guyant-Marechal, Thierry Kuntzer, Ioana Maria Ion, Anne-Sophie Lia, Jérôme Bouligand, 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}
Andreas Törnell, Nina Lagerström, Natalia Mossberg, Roberta Kiffin, Helen Farman, Jan Lycke, Oluf Andersen, Markus Axelsson, Kristoffer Hellstrand, Anna Martner
Background and Aims
Guillain–Barré syndrome (GBS) is a rare, acute neuropathy characterized by ascending muscle weakness. Age, axonal GBS variants, and antecedent Campylobacter jejuni infection are associated with severe GBS, but the detailed mechanisms of nerve damage are only partly explored. Pro-inflammatory myeloid cells express NADPH oxidases (NOX) that generate tissue-toxic reactive oxygen species (ROS) that are implicated in neurodegenerative diseases. This study analyzed the impact of variants of the gene encoding the functional NOX subunit CYBA (p22phox) on acute severity, axonal damage, and recovery in adult GBS patients.
Methods
Extracted DNA from 121 patients was genotyped for allelic variation at rs1049254 and rs4673 within CYBA using real-time quantitative polymerase chain reaction. Serum neurofilament light chain was quantified by single molecule array. Patients were followed for severity and motor function recovery for up to 13 years.
Results
CYBA genotypes linked to reduced formation of ROS, i.e. rs1049254/G and rs4673/A, were significantly associated with unassisted ventilation, shorter time to normalization of serum neurofilament light chain and shorter time to regained motor function. Residual disability at follow-up was confined to patients carrying CYBA alleles associated with high formation of ROS.
Interpretation
These findings implicate NOX-derived ROS in GBS pathophysiology and CYBA alleles as biomarkers of severity.
{"title":"CYBA allelic variants are associated with severity and recovery in Guillain–Barré syndrome","authors":"Andreas Törnell, Nina Lagerström, Natalia Mossberg, Roberta Kiffin, Helen Farman, Jan Lycke, Oluf Andersen, Markus Axelsson, Kristoffer Hellstrand, Anna Martner","doi":"10.1111/jns.12571","DOIUrl":"10.1111/jns.12571","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Guillain–Barré syndrome (GBS) is a rare, acute neuropathy characterized by ascending muscle weakness. Age, axonal GBS variants, and antecedent <i>Campylobacter jejuni</i> infection are associated with severe GBS, but the detailed mechanisms of nerve damage are only partly explored. Pro-inflammatory myeloid cells express NADPH oxidases (NOX) that generate tissue-toxic reactive oxygen species (ROS) that are implicated in neurodegenerative diseases. This study analyzed the impact of variants of the gene encoding the functional NOX subunit CYBA (p22<sup>phox</sup>) on acute severity, axonal damage, and recovery in adult GBS patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Extracted DNA from 121 patients was genotyped for allelic variation at rs1049254 and rs4673 within <i>CYBA</i> using real-time quantitative polymerase chain reaction. Serum neurofilament light chain was quantified by single molecule array. Patients were followed for severity and motor function recovery for up to 13 years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p><i>CYBA</i> genotypes linked to reduced formation of ROS, i.e. rs1049254/<b>G</b> and rs4673/<b>A</b>, were significantly associated with unassisted ventilation, shorter time to normalization of serum neurofilament light chain and shorter time to regained motor function. Residual disability at follow-up was confined to patients carrying <i>CYBA</i> alleles associated with high formation of ROS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>These findings implicate NOX-derived ROS in GBS pathophysiology and <i>CYBA</i> alleles as biomarkers of severity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"28 3","pages":"407-414"},"PeriodicalIF":3.8,"publicationDate":"2023-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.12571","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10192841","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}
Yael Eshed-Eisenbach, Peter J. Brophy, Elior Peles
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.
{"title":"Nodes of Ranvier in health and disease","authors":"Yael Eshed-Eisenbach, Peter J. Brophy, 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}
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