Journal of the Peripheral Nervous System最新文献

{"title":"VRK1-Related Motor Neuropathy With Upper Motor Neuron Signs and Selective Muscle Involvement","authors":"Manoella Guerra de Albuquerque Bueno, Diogo Fernandes dos Santos, Alexander M. Rossor, Matilde Laura, Alejandro Horga, Rodrigo Siqueira Soares Frezatti, Eduardo Vaz de Sousa Ferreira, Julian C. Blake, Jasper M. Morrow, Mary M. Reilly, Wilson Marques Júnior, Pedro José Tomaselli","doi":"10.1111/jns.70145","DOIUrl":"10.1111/jns.70145","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Hereditary motor neuropathies (HMN) represent a heterogeneous group of disorders with wide clinical and genetic variability. Despite advances in molecular diagnostics, approximately 50% of cases remain genetically unresolved, particularly those where distinguishing length-dependent motor neuropathy from motor neuron disorder with disproportionate segmental involvement is a challenge. Variants in the VRK1 gene, originally described in association with pontocerebellar hypoplasia, are now known to produce a broad clinical spectrum, including amyotrophic lateral sclerosis, dHMN, and less frequently, spastic paraplegia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This study's aim was to characterize the clinical presentation, electrophysiological findings, and muscle MRI patterns associated with VRK1-related motor neuron disease in a cohort of nine patients from five unrelated families.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Five unrelated families with inherited motor neuropathy were investigated using next-generation sequencing techniques, including targeted gene panels or whole-exome sequencing, with subsequent confirmation by Sanger sequencing. A total of nine affected individuals underwent detailed clinical evaluation, nerve conduction studies (NCS), electromyography (EMG), and whole-body muscle MRI (wbMRI).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Nine affected individuals carrying biallelic VRK1 variants were evaluated. In most cases (66%), symptom onset occurred during the first decade of life. All patients presented with gradually progressive distal muscle weakness. Mean Medical Research Council (MRC) scores were 2.8 for ankle dorsiflexion and 1.9 for plantar flexion. Sensory nerve conduction studies were normal in all individuals evaluated (8/9), although mild sensory complaints were reported in four patients. Muscle cramps were observed in two-thirds of the cohort, while fasciculations were uncommon (11%). EMG findings consistently demonstrated a neurogenic pattern with predominant distal involvement, and evidence of both acute and chronic denervation was present in four patients. Whole-body muscle MRI, available for all patients, revealed a consistent pattern of fatty infiltration predominantly affecting posterior muscle compartments, with minimal STIR signal changes. Brain and spinal imaging, performed in all individuals, showed no abnormalities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretations</h3>\u0000 \u0000","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"31 3","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.70145","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148447473","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":"The Erasmus—Polyneuropathy Symptom Score for the Screening of Chronic Axonal Polyneuropathy: A Validation Study","authors":"Noor E. Taams,&nbsp;Merel Huijg,&nbsp;Frederique H. Vermeij,&nbsp;Krista Kuitwaard,&nbsp;Rens Hanewinckel,&nbsp;Janet de Beukelaar,&nbsp;Evan L. Reynolds,&nbsp;Brian C. Callaghan,&nbsp;M. Arfan Ikram,&nbsp;Pieter A. van Doorn","doi":"10.1111/jns.70143","DOIUrl":"10.1111/jns.70143","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Chronic axonal polyneuropathy is a common disorder that often remains undiagnosed. Early detection may enhance treatment of underlying risk factors and prevent long-term complications. The Erasmus-Polyneuropathy symptom score (E-PSS) is a simple and rapid screening tool, consisting of six questions (score ranges 0–14). This study aims to validate the E-PSS in a non-academic population and compare its performance with the commonly used Michigan Neuropathy Screening Instrument questionnaire (MNSIq).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This validation study was performed at two non-academic neurology outpatient clinics in the Netherlands. Patients visiting the outpatient clinic, regardless of the reason for referral, were eligible for inclusion if aged ≥ 18 years and able to fill in the questionnaire. The gold standard definition of chronic axonal polyneuropathy was based on the diagnosis made by the treating physician. The discriminative performance was evaluated using the area under the curve (AUC) of the receiver operating curves (ROC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>From February 2020 until October 2021, 818 participants were included, of whom 222 had chronic axonal polyneuropathy (27%). Median age was 62 years (IQR 49–73) and 59% were female (<i>N</i> = 479). The median E-PSS score in participants with polyneuropathy was 6 (IQR 3–8) and in participants without polyneuropathy 1 (IQR 0–4). The performance of the E-PSS was good (AUC 0.81, 95% CI 0.77–0.84) and better than the MNSIq (AUC 0.65, 95% CI 0.61–0.69) (The DeLong test; <i>p</i> &lt; 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>The E-PSS is a fast and easy-to-use questionnaire with good AUC-determined discriminative performance between participants with and without chronic axonal polyneuropathy in non-academic neurology outpatient settings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"31 3","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.70143","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148437007","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":"Boy in the Barrel: Excruciating Paroxysmal Pain Disorder Associated With an SCN9A Gain-of-Function Variant","authors":"Pedro Jose Tomaselli,&nbsp;Rodrigo Siqueira Soares Frezatti,&nbsp;Christopher J. Record,&nbsp;Maria Cristina Lopes Schiavoni,&nbsp;Natalia Dominik,&nbsp;Jana Vandrovcova,&nbsp;Mary M. Reilly,&nbsp;Wilson Marques Jr","doi":"10.1111/jns.70142","DOIUrl":"10.1111/jns.70142","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Gain-of-function variants in SCN9A, encoding the Nav1.7 sodium channel, cause inherited painful neuropathic disorders. We report a young man with severe childhood-onset heat-triggered paroxysmal pain, autonomic dysfunction, skeletal abnormalities, and a de novo SCN9A p.Ile234Thr variant, emphasizing the diagnostic and therapeutic relevance of comprehensive phenotyping.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case Report</h3>\u0000 \u0000 <p>The patient developed excruciating lower-limb pain in early childhood, partially relieved by prolonged immersion in cold running water. Evaluation demonstrated marked small-fibre dysfunction, absent sympathetic skin responses, impaired sweating, absent lower-limb pain-related evoked potentials, loss of dermal and epidermal nerve fibres, pronounced small myelinated fibre loss on sural nerve biopsy, and mild large-fibre involvement. Whole-exome sequencing identified the de novo pathogenic SCN9A variant c.701 T&gt;C; p.Ile234Thr. Carbamazepine led to more than 90% pain improvement and substantial functional recovery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>This case expands the clinical spectrum associated with SCN9A p.Ile234Thr and illustrates how genetic diagnosis may directly guide treatment. The associated large-fibre abnormalities and acetabular dysplasia are interpreted cautiously, as their relationship to SCN9A dysfunction remains uncertain.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"31 3","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.70142","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148430548","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":"Development and Inter-Laboratory Validation of Multiplex Flow Cytometry Assay for Autoimmune Nodopathy","authors":"Young Gi Min,&nbsp;Paula Llarch,&nbsp;Cinta Lleixà,&nbsp;Woohee Ju,&nbsp;Ha Young Shin,&nbsp;Jae Jun Ban,&nbsp;Luis Querol,&nbsp;Jung-Joon Sung","doi":"10.1111/jns.70137","DOIUrl":"10.1111/jns.70137","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Purpose</h3>\u0000 \u0000 <p>Autoimmune nodopathies (AN) are a group of rare disorders caused by autoantibodies targeting cell-adhesion molecules located at the node of Ranvier. Reliable and efficient antibody testing for AN has become essential for optimal care of autoimmune neuropathies. In this study, we developed a multiplex flow cytometry (FCM) assay capable of simultaneously detecting four major AN antibodies and validated its diagnostic performance through inter-laboratory collaboration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Multiplex FCM assay was established using live cell lines stably expressing each of the four AN targets—neurofascin-155 (NF155), contactin-1 (CNTN1), contactin-associated protein 1 (CASPR1), and NF186. Using this assay, we tested 87 serum samples (46 AN, 39 disease controls, and 2 healthy controls) and compared the results with those obtained by enzyme linked immunosorbent assay (ELISA), fixed and/or live cell-based assay (CBA) conducted at an independent laboratory. IgG4 subclass positivity and autoantibody titers were also analyzed and compared between multiplex FCM assay and ELISA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Multiplex FCM assay demonstrated excellent diagnostic performance, with overall sensitivity of 95.1%, specificity of 97.8%, and accuracy of 99.6%. IgG4 subclass was detected in approximately 80% of AN sera, showing high concordance with ELISA. Antibody titers showed positive correlations between ELISA end-point titers and FCM-derived fluorescence intensity values.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This multiplex FCM assay enables rapid, objective, and quantitative detection of AN autoantibodies and the presence of IgG4 subclass using minimal sample volume. High sensitivity and specificity support its potential utility for routine serological testing for AN.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"31 3","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148430714","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":"Impact of Gut Microbiota Dysbiosis in Treatment Outcomes of Guillain-Barré Syndrome","authors":"Shoma Hayat,&nbsp;Md. Abu Jaher Nayeem,&nbsp;Asaduzzaman Asad,&nbsp;Md. Golam Mostafa,&nbsp;Ruma Begum,&nbsp;Moriam Akter Munni,&nbsp;Ayesha Akter Anjuman,&nbsp;Saima Akhter Sadia,&nbsp;Ismat Jahan Upama,&nbsp;Imran Hasan,&nbsp;Quazi Deen Mohammad,&nbsp;Zhahirul Islam","doi":"10.1111/jns.70141","DOIUrl":"10.1111/jns.70141","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>The gut-microbiota plays a significant role in neuro-autoimmune diseases, like Guillain-Barré syndrome (GBS), a post-infectious disorder of the peripheral nervous system (PNS). By altering host immunity, gut dysbiosis may impact the standard therapeutic efficacy of intravenous immunoglobulin (IVIg) and plasma exchange (PE) and thereby, disease progression in GBS. In this study, we investigated the impact of gut-microbiota diversity on therapeutic outcomes of IVIg and PE in patients with GBS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We enrolled 60 patients with GBS categorized into three treatment groups: IVIg-treated, PE, and supportive-care along with 60 age-sex-matched healthy controls from Bangladesh. Fecal microbial DNA was extracted at different timepoints and sequenced. Clinical and sequenced data were analyzed using the Qiime2-Dada2 pipeline.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Gut-microbial diversity significantly differed in patients with GBS before and after treatment (Shannon: <i>p</i> = 0.037; Evenness: <i>p</i> = 0.012), particularly in IVIg-treated patients, showing significant changes after 6-month treatment (Shannon: <i>p</i> = 0.034; Evenness: <i>p</i> = 0.011). Beta diversity indicated microbiota restoration in IVIg-treated patients toward a healthy state after treatment (<i>p</i> ≤ 0.001). Phylum Actinobacteriota (<i>p</i> = 0.026), genera <i>Bifidobacterium</i> (<i>p</i> = 0.006), and <i>Enterococcus</i> (<i>p</i> ≤ 0.0001) were relatively abundant in severe patients. Mechanically ventilated patients showed significant gut-microbial diversity (Unweighted-UniFrac; <i>p</i> ≤ 0.001). Biomarker analysis identified a higher abundance of Eubacterium, Bacteroides, <i>Escherichia-Shigella</i>, and <i>Actinomyces</i> in GBS patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Our exploratory study indicates that gut microbiota dysbiosis is associated with GBS severity and IVIg-treatment outcomes. IVIg-treatment promoted partial restoration of microbial diversity, suggesting a potential immunomodulatory effect mediated through the microbiota. Further studies using meta-transcriptomics are warranted to define functional consequences of microbial shifts in treatment responses of GBS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"31 3","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148422081","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":"Use of Intravenous Immunoglobulin Therapy for Small Fiber Neuropathy: A Systematic Review of Current Clinical Evidence","authors":"Qin Xiang Ng,&nbsp;Klarisse Man Ling Neo,&nbsp;Boxuan Zhang,&nbsp;Zhao Cheng Yeo,&nbsp;Phireethi Natarajan Anitha,&nbsp;Amanda Chee Yun Chan","doi":"10.1111/jns.70138","DOIUrl":"10.1111/jns.70138","url":null,"abstract":"<div>\u0000 \u0000 <p>Small fiber neuropathy (SFN) is a clinically heterogeneous and difficult-to-manage condition for which intravenous immunoglobulin (IVIG) is increasingly used despite inconsistent evidence and substantial cost. We therefore systematically evaluated the clinical effectiveness of IVIG in SFN, with attention to the variation across etiological subtypes. In accordance with PRISMA 2020 guidelines, the review protocol was registered in PROSPERO (CRD420251247780). PubMed, Embase, and the Cochrane Library databases were searched from inception to 31 August 2025. Eligible studies included adults with clinically or histologically confirmed SFN receiving IVIG, reporting at least one predefined outcome. Two reviewers independently screened and extracted data. Risk of bias was assessed, and certainty of evidence was evaluated using GRADE. Due to heterogeneity, a narrative synthesis was performed. A total of seven studies (2 randomized controlled trials [RCTs], 5 observational studies) involving 165 IVIG-treated patients were included. RCTs in idiopathic or broadly defined SFN showed no significant benefit of IVIG over placebo in pain reduction, autonomic symptoms, quality of life, or intraepidermal nerve fiber density. In contrast, observational studies reported improvements in pain, autonomic function, and, in some cases, nerve fiber density, particularly in autoimmune-associated SFN subtypes. However, these studies were limited by small sample sizes, lack of controls, and high risk of bias. GRADE assessment indicated low to very low certainty of evidence across outcomes. Current evidence does not support routine IVIG use in SFN. Apparent benefits in selected immune-mediated subtypes remain inconclusive and warrant further research with biologically stratified, adequately powered trials.</p>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"31 3","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412275","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":"De Novo MFN2 p.Arg95Met in Severe Charcot-Marie-Tooth Disease Type 2A","authors":"Hsi-Yen Lee,&nbsp;Wen-Ling Cheng,&nbsp;Shin-Hung Pan,&nbsp;Chia-Ju Lee,&nbsp;Yau-Huei Wei,&nbsp;Chin-San Liu","doi":"10.1111/jns.70136","DOIUrl":"https://doi.org/10.1111/jns.70136","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Mitofusin 2 (MFN2)-related Charcot–Marie–Tooth disease type 2A (CMT2A) is often associated with early onset, severe progressive weakness, distal wasting, and reduced motor and sensory response amplitudes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case Report</h3>\u0000 \u0000 <p>We report a 30-year-old Taiwanese woman with infancy-onset, severe axonal sensorimotor neuropathy, progressive distal weakness and wasting, optic atrophy, bilateral sensorineural hearing loss, hypophonia, and wheelchair dependence from adolescence. Nerve conduction study was consistent with severe chronic axonal sensorimotor polyneuropathy. Whole-exome sequencing identified a heterozygous de novo Mitofusin 2 (MFN2) variant, NM_014874.4:c.284G&gt;T, predicting p.Arg95Met.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>This case expands the genotypic spectrum of MFN2-related Charcot–Marie–Tooth disease type 2A and supports the clinical importance of the Arg94/Arg95 region in severe early-onset MFN2 neuropathy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"31 3","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148306136","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":"Autonomic Nervous System Phenotyping Across Chronic Demyelinating Peripheral Neuropathies: A Comparative Study","authors":"Bogdan Bjelica,&nbsp;Teodora Todorovic,&nbsp;Ivo Bozovic,&nbsp;Aleksa Palibrk,&nbsp;Vladimir Jankovic,&nbsp;Ivana Basta,&nbsp;Stojan Peric","doi":"10.1111/jns.70135","DOIUrl":"https://doi.org/10.1111/jns.70135","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>This study aimed to systematically phenotype autonomic nervous system (ANS) involvement in patients with chronic inflammatory demyelinating polyneuropathy (CIDP), monoclonal gammopathy of undetermined significance-associated neuropathy (MGUS-PNP), Charcot–Marie–Tooth disease Type 1A (CMT1A), and hereditary neuropathy with liability to pressure palsies (HNPP).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Autonomic symptoms were assessed using the SCales for Outcomes in Parkinson's Disease-Autonomic Dysfunction (SCOPA-AUT). Muscle strength and functional disability were evaluated using the Medical Research Council (MRC) scale, the Inflammatory Neuropathy Cause and Treatment (INCAT) disability scale, and the Overall Neuropathy Limitation Scale (ONLS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 343 participants were included: 98 with CIDP (mean age: 59.2 ± 13.2 years), 51 with MGUS-PNP (66.0 ± 11.3 years), 51 with CMT1A (51.2 ± 13.1 years), 18 with HNPP (40.6 ± 15.1 years), and 125 healthy controls (58.2 ± 13.3 years). Compared with healthy controls, patients with CIDP, MGUS-PNP, and CMT1A showed significantly higher total SCOPA-AUT scores (<i>p</i> &lt; 0.01). Distinct, disease-specific ANS symptom patterns were observed across neuropathy subtypes. Overall disability was independently associated with overall autonomic symptom burden in MGUS-PNP (<i>β</i> = 0.42, <i>p</i> &lt; 0.05) and CMT1A (<i>β</i> = 0.68, <i>p</i> &lt; 0.05). In CIDP, patients with active disease showed higher autonomic symptom burden than those with inactive disease (12.7 ± 11.7 vs. 8.6 ± 7.9, <i>p</i> = 0.042).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Patients with CIDP, MGUS-PNP, and CMT1A exhibit a substantial autonomic symptom burden with distinct disease-specific ANS patterns. These findings highlight the relevance of autonomic dysfunction in immune-mediated and hereditary neuropathies and warrant further studies to clarify their clinical and prognostic significance.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"31 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.70135","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148282501","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":"Circulating Inflammation-Related Proteins Linked to Corneal Neuroimmune Measures, Neuropathy Deficits, and Symptoms in Type 2 Diabetes","authors":"Georgios Ponirakis,&nbsp;Ibrahim Al-Janahi,&nbsp;Einas Elgassim,&nbsp;Rajaa S. D. Dalloul,&nbsp;Ioannis N. Petropoulos,&nbsp;Hoda Gad,&nbsp;Adnan Khan,&nbsp;Hadeel B. Zaghloul,&nbsp;Hamda Ali,&nbsp;Mashhood A. Siddique,&nbsp;Fatima F. S. Mohamed,&nbsp;Lina H. M. Ahmed,&nbsp;Youssra Dakroury,&nbsp;Abeer M. M. El Shewehy,&nbsp;Ruba Saeid,&nbsp;Fadwa Mahjoub,&nbsp;Muna N. Al-Noubi,&nbsp;Hina Sarwath,&nbsp;Pradipta Paul,&nbsp;Ridhima Kaul,&nbsp;Iuliia Salivon,&nbsp;Mahmoud A. Zirie,&nbsp;Yousuf Al-Ansari,&nbsp;Stephen L. Atkin,&nbsp;Frank Schmidt,&nbsp;Rayaz A. Malik","doi":"10.1111/jns.70134","DOIUrl":"10.1111/jns.70134","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Systemic inflammation plays a key role in diabetic peripheral neuropathy (DPN). This exploratory study investigated circulating inflammation-related proteins associated with corneal neuroimmune measures, neuropathic deficits, and symptoms in patients with type 2 diabetes (T2D).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Participants with T2D (<i>n</i> = 44) underwent assessment of corneal nerve morphology and dendritic cell density (DCD), vibration perception threshold (VPT), electrochemical skin conductance (ESC), DN4 questionnaire, and profiling of 92 plasma proteins using the Olink inflammation panel.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 30 proteins were associated with neuropathy deficits and corneal DCD. Corneal nerve measures showed positive associations with two chemokines, four epithelial-barrier cytokines, and two growth-related mediators, and negative associations with three inflammatory cytokines/receptors, one anti-inflammatory cytokine/receptor, two immune-regulatory molecules, and one chemokine. VPT was positively associated with three inflammatory cytokines/receptors, while ESC showed negative associations with one metabolic–inflammatory enzyme, one chemokine, and one inflammatory receptor. Neuropathic symptoms based on DN4 were positively associated with one immune-regulatory molecule and negatively with one neurotrophic factor and one homeostatic cytokine. Corneal DCD showed positive associations with four inflammatory cytokines and one neurotrophic factor, and a negative association with one epithelial chemokine. Non-branching DCD was negatively associated with corneal nerve branch density (<i>p</i> ≤ 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Neuropathy deficits and corneal DCD in T2D are associated with distinct neuroimmune pathways.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"31 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148218296","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":"A Quantitative Assessment of Upper Limb Motor Function Across Disease Stages in Hereditary Transthyretin Amyloidosis","authors":"Mehrnaz Hamedani,&nbsp;Valeria Prada,&nbsp;Sara Massucco,&nbsp;Edoardo Roveta,&nbsp;Marina Grandis,&nbsp;Chiara Gemelli,&nbsp;Irene Schiavetti,&nbsp;Alessio Signori,&nbsp;Cristina Schenone,&nbsp;Marco Luigetti,&nbsp;Valeria Guglielmino,&nbsp;Maria Ausilia Sciarrone,&nbsp;Francesca Vitali,&nbsp;Luca Guglielmo Pradotto,&nbsp;Fiore Manganelli,&nbsp;Stefano Tozza,&nbsp;Giovanni Palumbo,&nbsp;Anna Mazzeo,&nbsp;Luca Gentile,&nbsp;Massimo Russo,&nbsp;Marcella De Luca,&nbsp;Federica D'Arma,&nbsp;Chiara Pisciotta,&nbsp;Silvia Fenu,&nbsp;Davide Pareyson,&nbsp;Angelo Schenone","doi":"10.1111/jns.70127","DOIUrl":"10.1111/jns.70127","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Hereditary transthyretin amyloidosis (ATTRv) is a multisystemic disease where early neuropathy signs are challenging to detect conventionally. This study aimed to evaluate hand motor performance in ATTRv using the Hand Test System (HTS) across disease stages and examine correlations with standard measures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 113 individuals were enrolled: 74 patients with ATTRv (divided according to Familial Amyloid Polyneuropathy [FAP] stage into FAP0: pre-symptomatic with confirmed <i>TTR</i> mutations, <i>n</i> = 16; FAP1: mild sensory/motor symptoms, <i>n</i> = 40; FAP2: ambulatory with assistance, <i>n</i> = 18) and 39 healthy controls. All participants underwent HTS evaluation; 9-Hole Peg Test (9HPT); handgrip and tripod pinch strength testing; Thumb Opposition Test (TOT); Neuropathy Impairment Score (NIS); Disabilities of the Arm, Shoulder and Hand questionnaire (DASH); and Quality of Life Diabetic Neuropathy (Norfolk QoL-DN) questionnaire. Group differences were analyzed with analysis of covariance and correlations with Pearson's coefficients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>HTS parameters (Touch Duration, Inter-Tapping Interval, Movement Rate) significantly differed across stages between the FAP2 and all other groups, with some parameters distinguishing the FAP1 from the control and FAP0 groups. 9HPT impairment was observed only in the FAP2 group. Grip strength showed subtle changes, especially in the right hands of the FAP1 group, while tripod pinch strength declined during advanced stages. Several HTS parameters were correlated with NIS, DASH, Norfolk QoL-DN, and hand strength. Subclinical carpal tunnel syndrome possibly influenced early-stage results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>HTS detected stage-related motor differences in ATTRv and correlated them with standard measures, offering increased sensitivity to early neuropathic changes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"31 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.70127","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148163784","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}