Journal of the Peripheral Nervous System最新文献

{"title":"Genetic, electrophysiological, and pathological studies on patients with SCN9A-related pain disorders","authors":"Jun-Hui Yuan,&nbsp;Xiaoyang Cheng,&nbsp;Eiji Matsuura,&nbsp;Yujiro Higuchi,&nbsp;Masahiro Ando,&nbsp;Akihiro Hashiguchi,&nbsp;Akiko Yoshimura,&nbsp;Ryo Nakachi,&nbsp;Jun Mine,&nbsp;Takeshi Taketani,&nbsp;Kenichi Maeda,&nbsp;Saori Kawakami,&nbsp;Ryutaro Kira,&nbsp;Shoko Tanaka,&nbsp;Kazuaki Kanai,&nbsp;Fadia Dib-Hajj,&nbsp;Sulayman D. Dib-Hajj,&nbsp;Stephen G. Waxman,&nbsp;Hiroshi Takashima","doi":"10.1111/jns.12590","DOIUrl":"10.1111/jns.12590","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Voltage-gated sodium channel Nav1.7, encoded by the <i>SCN9A</i> gene, has been linked to diverse painful peripheral neuropathies, represented by the inherited erythromelalgia (EM) and paroxysmal extreme pain disorder (PEPD). The aim of this study was to determine the genetic etiology of patients experiencing neuropathic pain, and shed light on the underlying pathogenesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We enrolled eight patients presenting with early-onset painful peripheral neuropathies, consisting of six cases exhibiting EM/EM-like disorders and two cases clinically diagnosed with PEPD. We conducted a gene-panel sequencing targeting 18 genes associated with hereditary sensory and/or autonomic neuropathy. We introduced novel <i>SCN9A</i> mutation (F1624S) into a GFP-2A-Nav1.7rNS plasmid, and the constructs were then transiently transfected into HEK293 cells. We characterized both wild-type and F1624S Nav1.7 channels using an automated high-throughput patch-clamp system.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>From two patients displaying EM-like/EM phenotypes, we identified two <i>SCN9A</i> mutations, I136V and P1308L. Among two patients diagnosed with PEPD, we found two additional mutations in <i>SCN9A</i>, F1624S (novel) and A1632E. Patch-clamp analysis of Nav1.7-F1624S revealed depolarizing shifts in both steady-state fast inactivation (17.4 mV, <i>p</i> &lt; .001) and slow inactivation (5.5 mV, <i>p</i> &lt; .001), but no effect on channel activation was observed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Clinical features observed in our patients broaden the phenotypic spectrum of <i>SCN9A</i>-related pain disorders, and the electrophysiological analysis enriches the understanding of genotype–phenotype association caused by Nav1.7 gain-of-function mutations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"28 4","pages":"597-607"},"PeriodicalIF":3.8,"publicationDate":"2023-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10021484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ophthalmological involvement in wild-type transthyretin amyloidosis: A multimodal imaging study","authors":"Luisa Frizziero,&nbsp;Alessandro Salvalaggio,&nbsp;Eleonora Cosmo,&nbsp;Alberto Cipriani,&nbsp;Edoardo Midena,&nbsp;Chiara Briani","doi":"10.1111/jns.12589","DOIUrl":"10.1111/jns.12589","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Ophthalmological abnormalities have been reported in hereditary transthyretin-related amyloidosis (ATTRv, v for variant) but not in wild-type transthyretin-related amyloidosis (ATTRwt).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients with ATTRwt, ATTRv, and light chain amyloidosis (AL) and healthy subjects (controls) underwent complete eye examination, including optical coherence tomography (OCT), OCT angiography (OCTA), and in vivo corneal confocal microscopy (CCM).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Seventeen ATTRwt, nine ATTRv, two ATTRv carriers, and seven AL patients were enrolled. Compared with other groups, ATTRwt patients had 10 letters lower visual acuity and a higher prevalence of glaucoma, cataract, and retinal pigment epithelium alterations. In the whole group of patients, especially in ATTRwt, we observed (1) a reduced corneal nerve fiber length and more tortuous stromal nerves at CCM, (2) a reduced macular volume and peripapillary nerve fiber layer thickness at OCT, and (3) impairment of peripapillary and macular vascularization at OCTA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Ophthalmological abnormalities are common in ATTRwt, significantly impairing visual acuity. Noninvasive imaging modalities allow for the identification of small nerve fibers and small vessel damage, which may represent further warning signs for early diagnosis of ATTRwt.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"28 4","pages":"586-596"},"PeriodicalIF":3.8,"publicationDate":"2023-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.12589","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10135095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"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":"Evidence for spontaneous regulation of the humoral IgM anti-GM1 autoimmune response by IgG antibodies in multifocal motor neuropathy patients","authors":"Marianna Di Egidio,&nbsp;Cristian R. Bacaglio,&nbsp;Rocio Arrejoría,&nbsp;Andrés M. Villa,&nbsp;Gustavo A. Nores,&nbsp;Pablo H. H. Lopez","doi":"10.1111/jns.12583","DOIUrl":"10.1111/jns.12583","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Multifocal motor neuropathy (MMN) is a peripheral nerve disorder characterized by slow progressive distal asymmetric weakness with minimal or no sensory impairment. Currently, a vast evidence supports a direct pathogenic role of IgM anti-GM1 antibodies on disease pathogenesis. Patients with MMN seropositive for GM1-specific IgM antibodies have significantly more weakness, disability and axon loss than patients without these antibodies. During the screening for IgM anti-GM1 antibodies in a cohort of patients with neuropathy we noticed an absence or significant reduction of natural IgM anti-GM1 autoreactivity in some patients with MMN, suggesting a mechanism of self-control of autoreactivity. We aim to understand the lack of natural reactivity against GM1 in MMN patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The presence of free IgM anti-GM1 reactivity or its complex to blocking IgG was analysed by combining high performance thin layer chromatography-immunostaining, soluble binding inhibition assays, Protein-G or GM1-affinity columns and dot blot assays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified in MMN patients an immunoregulation of IgM anti-GM1 antibodies mediated by IgG immunoglobulins characterized by: (i) lack of natural IgM anti-GM1 autoreactivity as a result of a immunoregulatory IgG-dependent mechanism; (ii) presence of natural and disease-associated IgM anti-GM1/IgG blocking Ab complexes in sera; and (iii) high levels of IgG blocking against natural IgM anti-GM1 antibodies (Abs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Our observations unmask a spontaneous IgG-dependent mechanism of immunoregulation against IgM anti-GM1 antibodies that could explain, in part, fluctuations in the usually slowly progressive clinical course that characterizes the disease and, at the same time, allows the identification of an autoimmune response against GM1 ganglioside in seronegative patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"28 3","pages":"398-406"},"PeriodicalIF":3.8,"publicationDate":"2023-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10186265","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":"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":"Cardiovascular autonomic neuropathy in patients with type 2 diabetes with and without sensorimotor polyneuropathy","authors":"Emil Peters,&nbsp;Mustapha Itani,&nbsp;Alexander G. Kristensen,&nbsp;Astrid Juhl Terkelsen,&nbsp;Thomas Krøigård,&nbsp;Hatice Tankisi,&nbsp;Troels S. Jensen,&nbsp;Nanna B. Finnerup,&nbsp;Sandra Sif Gylfadottir","doi":"10.1111/jns.12580","DOIUrl":"10.1111/jns.12580","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Cardiovascular autonomic neuropathy (CAN) in patients with diabetes is associated with poor prognosis. We aimed to assess signs of CAN and autonomic symptoms and to investigate the impact of sensorimotor neuropathy on CAN by examining type 2 diabetes patients with (DPN [distal sensorimotor polyneuropathy]) and without distal sensorimotor polyneuropathy (noDPN) and healthy controls (HC). Secondarily, we aimed to describe the characteristics of patients with CAN.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A population of 374 subjects from a previously described cohort of the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) were included. Subjects were examined with the Vagus™ device for the diagnosis of CAN, where two or more abnormal cardiovascular autonomic reflex tests indicate definite CAN. Autonomic symptoms were assessed with Composite Autonomic Symptom Score 31 (COMPASS 31) questionnaire. DPN was defined according to the Toronto consensus panel definition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Definite CAN was present in 22% with DPN, 7% without DPN and 3% of HC, and 91% of patients with definite CAN had DPN. Patients with DPN and definite CAN reported higher COMPASS 31 scores compared to patients with noDPN (20.0 vs. 8.3, <i>p</i> &lt; 0.001) and no CAN (22.1 vs. 12.3, <i>p</i> = 0.01). CAN was associated with HbA1c and age in a multivariate logistic regression analysis but was not associated with IEFND or triglycerides.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>One in five patients with DPN have CAN and specific CAN characteristics may help identify patients at risk for developing this severe diabetic complication. Autonomic symptoms were strongly associated with having both DPN and CAN, but too unspecific for diagnosing CAN.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"28 3","pages":"450-459"},"PeriodicalIF":3.8,"publicationDate":"2023-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.12580","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10182602","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":"Phenotypic features of RETREG1-related hereditary sensory autonomic neuropathy","authors":"Arman Çakar,&nbsp;Gulandam Bagırova,&nbsp;Hacer Durmuş,&nbsp;Oya Uyguner,&nbsp;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 &gt; 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}

{"title":"Somatosensory profiling of patients undergoing alcohol withdrawal: Do neuropathic pain and sensory loss represent a problem?","authors":"Aurore Fernandez,&nbsp;Guillaume Graf,&nbsp;Aurélie Lasserre,&nbsp;Jean-Bernard Daeppen,&nbsp;Paul Chu Sin Chung,&nbsp;Chantal Berna,&nbsp;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}