Journal of the Peripheral Nervous System最新文献

{"title":"Clinical Development of Therapies for Charcot–Marie–Tooth Disease: Recommendations for Trial Design, Endpoints, and Regulatory Pathways","authors":"Charles K. Abrams,&nbsp;Sue Bruhn,&nbsp;Joshua Burns,&nbsp;Rebekah Fleming,&nbsp;Katherine Forsey,&nbsp;Vera Fridman,&nbsp;David N. Herrmann,&nbsp;Brian Lin,&nbsp;Susan McCune,&nbsp;Allison Moore,&nbsp;Susan Ruediger,&nbsp;Michael Shy,&nbsp;Shannon Strom,&nbsp;ToPIC:CMT Steering Committee","doi":"10.1111/jns.70146","DOIUrl":"10.1111/jns.70146","url":null,"abstract":"<p>Charcot–Marie–Tooth disease (CMT) encompasses a heterogeneous group of inherited peripheral neuropathies. Despite being the most common genetic neurological condition, individual CMT subtypes are rare, presenting unique challenges for therapeutic development. The Together Patients Industry Clinicians versus CMT (ToPIC: CMT) Advocacy Group was formed with a diverse group of patient advocacy groups, clinician-scientists who treat patients with CMT, and pharmaceutical industry representatives to develop a common guidance on development of new treatments for CMT with clear expectations for meaningful patient outcomes and objective assessments of improvement. The ToPIC: CMT Group developed recommendations for clinical development of drugs and biological products for treating CMT, addressing trial design considerations for this rare progressive disease. Key challenges in CMT include small patient populations, variable disease progression, and the need for sensitive outcome measures. Recommendations emphasize flexible trial designs including adaptive designs, external controls, and single-participant designs when scientifically justified. Where possible, broad inclusion criteria based on clinical phenotype rather than genetic subtype alone are recommended. Disease-specific, validated outcome measures should assess function across ages and disease stages. Biomarkers reflecting peripheral nervous system health may serve as surrogate endpoints to support accelerated approval pathways. Patient and care partner perspectives are essential throughout development, particularly regarding treatment goals, risk tolerance, and meaningful endpoints. Successful therapeutic development for CMT and related neuropathies requires innovative approaches that balance rigorous scientific standards with the realities of rare disease research. Regulatory flexibility, informed by patient input and natural history data, can facilitate efficient development while maintaining assurance of safety and effectiveness.</p>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"31 3","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13438117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148673966","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 Burden of Small Fiber Neuropathy: Changes in Pain, Costs, and Quality of Life Before and After Diagnosis","authors":"Dennis Kool,&nbsp;Margot Geerts,&nbsp;Lloyd Brandts,&nbsp;Merel Kimman,&nbsp;Caroline M. L. Gorissen-Brouwers,&nbsp;Catharina G. Faber,&nbsp;Ingemar S. J. Merkies,&nbsp;Janneke G. J. Hoeijmakers","doi":"10.1111/jns.70153","DOIUrl":"10.1111/jns.70153","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Small fiber neuropathy (SFN) is a peripheral neuropathy causing neuropathic pain, reduced quality of life (QoL), and high societal costs. Previous studies assessed these societal costs before a definitive diagnosis was established, leaving it unclear whether diagnostic confirmation affects costs, pain intensity, or QoL. This study assessed changes in these outcomes before and after diagnosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients referred to the tertiary SFN expertise center in the Netherlands completed questionnaires before diagnosis (at placement on the waiting list, approximately 7 months before consultation) and at 3 and/or 6 months after confirmation. Healthcare utilization, patient and family costs, and productivity losses were assessed using the iMTA Medical Consumption and Productivity Cost Questionnaires. QoL was measured with the EQ-5D-5L and pain intensity with a numeric rating scale. Missing data were handled using multiple imputation, and changes over time were analyzed using within-subject comparisons and generalized linear mixed models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Eighty-four patients completed both pre- and postdiagnosis questionnaires. After follow-up, total healthcare costs, patient and family costs, productivity losses, pain intensity, and QoL remained unchanged. However, diagnostic confirmation of SFN was associated with fewer medical specialist visits, lower related costs, and improved health perception.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>These findings suggest that diagnostic clarification alone is insufficient to reduce the overall burden of SFN, highlighting the need for more effective symptom management and supportive care strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"31 3","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13429313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663978","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":"Neurophysiological Characteristics of Nitrous Oxide-Induced Polyneuropathy: A Case Series","authors":"Tanya Elisabeth Bentley,&nbsp;Volker Limmroth,&nbsp;Maximilian Zimmermann,&nbsp;Johannes Fabian Holle","doi":"10.1111/jns.70156","DOIUrl":"https://doi.org/10.1111/jns.70156","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Nitrous oxide (N₂O) misuse is a growing health concern, with N₂O-induced neurological disorders increasingly reported across Europe. Among these, N₂O-induced polyneuropathy (PNP) can lead to permanent deficits, yet its neurophysiological characteristics remain inconsistently described. This retrospective case series aimed to characterize the electrophysiological pattern of N₂O-induced polyneuropathy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We reviewed the records of 12 patients with acute neurological symptoms and a history of N₂O abuse, all of whom underwent electrophysiological testing at a German tertiary care hospital between July 2023 and December 2024. Data were analyzed descriptively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Conduction studies revealed evidence of PNP in eight out of 12 patients and the most common pattern was pure motor (5/8). No distinct clinical phenotype could be identified for patients with electrophysiologically confirmed PNP or Pure-Motor PNP. SSEPs were abnormal in all assessable patients, whereas signs of SCD on MRI were present in a smaller proportion. Only three of 10 tested patients had reduced vitamin B12 levels, while all showed elevated methylmalonic acid (MMA) levels. Mean MMA levels were higher in patients with PNP than in those without.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>The reason why N₂O leads to different patterns of PNP remains unclear and a distinct phenotype for N₂O-induced PNP or Pure-Motor PNP was not found in this cohort. MMA represents a more reliable biomarker than serum vitamin B12 in the diagnostic workup of N₂O-induced neurotoxicity. These findings highlight the need for further research into additional neurotoxic properties of N₂O and individual predisposing factors underlying the different electrophysiological patterns of N₂O-induced PNP.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"31 3","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.70156","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148647809","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":"Molecular Mediators Associated With Myelination, Demyelination, and Remyelination in the Peripheral Nervous System","authors":"Kathleen Margaret Hagen,&nbsp;Shalina Sheryl Ousman","doi":"10.1111/jns.70148","DOIUrl":"10.1111/jns.70148","url":null,"abstract":"<p>The peripheral nervous system (PNS) is responsible for innervating all regions of the body outside of the central nervous system (CNS), the latter consisting of the brain, spinal cord, and optic nerves. While myelin is an essential component for the efficient functioning of both CNS and peripheral nerve cells, it is particularly important for PNS neurons since their cell bodies lie at considerable distances from their innervated targets. As such, regulation of myelin content and formation in the PNS is a carefully controlled process that involves many cellular and molecular players. The peripheral nerve is a multicellular environment containing several non-neuronal cell types such as fibroblasts, endothelial cells, pericytes, resident macrophages, and nonmyelinating and myelinating Schwann cells, all of which contribute to PNS homeostasis. This review focuses on the contributions of Schwann cells and macrophages and their molecular mediators in the formation, maintenance, degradation, and reformation of peripheral myelin during homeostasis of, and after damage to the PNS.</p>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"31 3","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148592336","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":"Biallelic SCO2 Variants Presenting as Motor-Predominant Axonal Neuropathy With Complex IV Deficiency","authors":"Adriana P. Rebelo,&nbsp;Katie Lutz,&nbsp;Tiffany Grider,&nbsp;Craig M. Zaidman,&nbsp;Michael E. Shy,&nbsp;Stephan Zuchner","doi":"10.1111/jns.70150","DOIUrl":"10.1111/jns.70150","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p><i>SCO2</i> encodes a mitochondrial copper chaperone required for cytochrome c oxidase (COX) assembly and is classically associated with severe multisystem mitochondrial disease. We characterize a motor-predominant axonal neuropathy presentation associated with biallelic SCO2 variants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Clinical, genetic, and functional studies were performed in a 15-year-old female presenting with axonal neuropathy. Functional studies were conducted in patient-derived fibroblasts, including Western blot analysis and spectrophotometric cytochrome c oxidation assay. Structural modeling was performed using ChimeraX.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The patient presented with a motor-predominant axonal neuropathy consistent with Charcot-Marie-Tooth (CMT) disease. Clinical genetic testing identified compound heterozygous <i>SCO2</i> variants of uncertain significance: a missense variant (p.Arg120Trp) and a frameshift variant (p.Asp252ValfsTer24). Structural modeling predicted disruption of protein stability for both variants. Functional studies in patient-derived fibroblasts demonstrated complete absence of SCO2 protein and reduced mitochondrial complex IV activity, supporting a loss-of-function mechanism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>These findings demonstrate that <i>SCO2</i>-related disease can present as an isolated axonal neuropathy, a phenotype that remains rarely reported. Our study also highlights the value of integrating in silico prediction tools with functional assays to establish pathogenicity in rare sporadic cases of inherited neuropathy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"31 3","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13395627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579133","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":"Spectrum of Hereditary Neuropathies in Adult Patients From Serbia","authors":"Milica Vukojevic,&nbsp;Ana Marjanovic,&nbsp;Vukan Ivanovic,&nbsp;Jovan Pesovic,&nbsp;Ana Kosac,&nbsp;Ayse Candayan,&nbsp;Milena Jankovic,&nbsp;Dusanka Savic-Pavicevic,&nbsp;Albena Jordanova,&nbsp;Ivana Basta,&nbsp;Stojan Peric","doi":"10.1111/jns.70149","DOIUrl":"10.1111/jns.70149","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Hereditary neuropathies are a group of genetically and phenotypically heterogeneous neuropathies. These are classified into: hereditary sensory motor neuropathy (HSMN) aka Charcot–Marie–Tooth disease (CMT), distal motor neuropathy (dMN), hereditary sensory autonomic neuropathy (HSAN), episodic neuropathies and polyneuropathy as part of a complex clinical presentation. The aim of this study was to determine final diagnoses in patients referred from the tertiary center in Serbia under suspicion of hereditary neuropathy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Materials</h3>\u0000 \u0000 <p>This research included 340 patients directed for genetic testing from the Neurology Clinic, University Clinical Center of Serbia during the period from 2009 to 2023, who underwent complete genetic analyses available.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The most prominent demyelinating neuropathy was group consisted of patients with CMT1A (93 (27.3%)), followed by CMT1B (10 (2.9%)). In the group of patients with axonal form of the disease, the most prevalent was the one with pathogenic variant in <i>HINT1</i> (18 (5.3%)). Nineteen (5.6%) patients have had variants in <i>GJB1</i> gene. DMN group was composed of seven (2%) patients. HSAN was final diagnosis in 2 (0.6%) patients. Group of 16 (4.7%) patients have had neuropathy as part of a complex clinical presentation. In 70 (20.6%) patients no significant genetic variant was found, even though clinical presentation was highly suggestive of hereditary neuropathy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>In line with other populations, CMT1A was the most common cause of hereditary neuropathy in Serbia. The axonal cohort predominantly included patients with variants in the HINT1 gene, which represents a population-specific characteristic. These findings highlight the importance of targeted genetic analysis in diagnosing hereditary neuropathies in certain populations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"31 3","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148536431","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":"Late-Onset Tay–Sachs Disease With SMALED-Like Muscle MRI Pattern Despite a Distinct Clinical Phenotype","authors":"Rodrigo Siqueira Soares Frezatti,&nbsp;Trajano Aguiar Pires Gonçalves,&nbsp;Manoella Guerra de Albuquerque Bueno,&nbsp;André Clériston José dos Santos,&nbsp;Lindsay A. Wilson,&nbsp;Natalia Dominik,&nbsp;Michael G. Hanna,&nbsp;Jasper Morrow,&nbsp;Alex M. Rossor,&nbsp;Mary M. Reilly,&nbsp;Pedro José Tomaselli,&nbsp;Wilson Marques Junior","doi":"10.1111/jns.70144","DOIUrl":"https://doi.org/10.1111/jns.70144","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Late-onset Tay–Sachs disease (LOTS) is a rare lysosomal disorder that contrasts with the classical infantile form by presenting with milder and heterogeneous neurological manifestations, including lower motor neuron phenotypes. While muscle MRI fatty infiltration patterns have been described in selected inherited motor neuron disorders, the corresponding imaging features in LOTS remain poorly defined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case</h3>\u0000 \u0000 <p>We report two female patients presenting in the second decade of life with slowly progressive, lower limb–predominant flaccid weakness associated with tremor. Hip flexion and arm extension were disproportionately affected. Electromyography demonstrated a neurogenic pattern. Whole-body muscle MRI (wbMRI) revealed selective fatty infiltration on T1-weighted sequences with normal STIR imaging. At the pelvic and thigh levels, this pattern showed marked overlap with the characteristic fatty infiltration described in SMA with lower extremity predominance (SMALED), including relative sparing of the adductor longus and semimembranosus. In contrast, consistent additional involvement of the iliopsoas and triceps brachii muscles was observed. Whole-exome sequencing identified compound heterozygous pathogenic variants in the HEXA gene in each patient, confirmed to be in trans, and enzymatic testing demonstrated reduced β-hexosaminidase A activity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>LOTS may reproduce key elements of the SMALED muscle MRI fatty infiltration pattern, particularly at the pelvic and thigh levels, while maintaining a distinct clinical presentation. Recognition of this partial radiological overlap, together with its discriminative features, is important to avoid diagnostic misclassification and to guide appropriate genetic testing.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"31 3","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.70144","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148467527","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":"Amyloid-Like Immunoglobulin Deposition Neuropathy","authors":"Christer Sawaya,&nbsp;Mark Fabian,&nbsp;Agustín Sancho Saldaña,&nbsp;Chinar Osman,&nbsp;Robert Hadden,&nbsp;Haider Katifi","doi":"10.1111/jns.70139","DOIUrl":"https://doi.org/10.1111/jns.70139","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Amyloid-like immunoglobulin deposition neuropathy is a rare cause of polyneuropathy, characterised by unique clinical and histological features in combination with proteomics that distinguish it from both amyloidosis and anti-MAG neuropathy. While light microscopic findings resemble amyloidosis with ‘amyloid-like deposits’, they are negative for Congo-red stain and have granular ultrastructure appearances under electron microscopy, unlike the characteristic fibrillary appearance of amyloid.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We present five cases of polyneuropathy associated with IgM paraprotein, without anti-MAG antibodies, with a distinctive phenotype: predominant neuropathic pain, skin changes or neuropathic ulcers, and a progressive distal sensory neuropathy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>All patients demonstrated an axonal sensorimotor neuropathy and histopathology of ‘amyloid-like’ (Congo-red negative) material with predominant granular deposition on electron microscopy consistent with a combination of heavy and light chain deposition. Skin involvement demonstrated similar histological features, but there was no evidence of renal or cardiac involvement. Most patients had treatment for their underlying haematological disorder and subsequently had no further progression in their neuropathy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Amyloid-like immunoglobulin deposition neuropathy is a slowly progressive painful axonal polyneuropathy associated with paraproteinaemia. Diagnosis is made with biopsy and electron microscopy. Treatment targets the source of the paraproteins and controls disease progression, leading to favourable survival compared to AL amyloidosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"31 3","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148467561","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":"Long-Term Safety and Efficacy of Efgartigimod PH20 in Chronic Inflammatory Demyelinating Polyradiculoneuropathy: ADHERE/ADHERE+ Trial Interim Analysis","authors":"Jeffrey A. Allen,&nbsp;Geoffrey Istas,&nbsp;Satoshi Kuwabara,&nbsp;Trevor Mole,&nbsp;Luis Querol,&nbsp;Simon Rinaldi,&nbsp;Mark Stettner,&nbsp;Benjamin Van Hoorick,&nbsp;Richard A. Lewis","doi":"10.1111/jns.70140","DOIUrl":"https://doi.org/10.1111/jns.70140","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>In ADHERE, subcutaneous efgartigimod PH20 (1000 mg once weekly) was effective and well tolerated in participants with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). ADHERE+ is an open-label extension of ADHERE assessing long-term safety and efficacy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Eligible participants from ADHERE run-in period (prior CIDP treatments discontinued), stage A (open-label efgartigimod), and stage B (stage A responders randomized to placebo or efgartigimod) could roll over to ADHERE+ and receive efgartigimod. The primary outcome was to assess long-term safety and tolerability. Efficacy outcomes evaluated adjusted Inflammatory Neuropathy Cause and Treatment (aINCAT) score, Inflammatory Rasch-built Overall Disability Scale (I-RODS) score, and mean grip strength (GS) from ADHERE run-in baseline through ADHERE+ week 36.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>At interim data cut-off (February 16, 2024), 228/229 eligible participants advanced to ADHERE+. Prolonged efgartigimod exposure did not increase the incidence (<i>n</i> = 171/228 [75.0%]) or severity of TEAEs (grade ≥ 3 TEAEs, <i>n</i> = 41/228 [18.0%]); regardless of immunoglobulin G level, there was a low incidence of infections. Stage A responders reported long-term clinically meaningful improvements in mean aINCAT (decreased by 1.2 points), I-RODS centile metric (increase of 8.8 points), and GS scores (increase of 17.5 kPa) from run-in baseline to ADHERE+ week 36, irrespective of stage B treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Interim results from ADHERE+ indicate long-term efgartigimod PH20 treatment in participants with CIDP was well tolerated (maximum exposure = 187.3 weeks; mean (SD) treatment duration = 58.0 [33.8] weeks). Clinically meaningful improvements in disability and strength were observed across assessments, regardless of stage B treatment or prior treatment status, with greater improvements seen over time.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"31 3","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.70140","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148467560","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":"Asymmetric Guillain–Barré Syndrome as a Stroke Mimic","authors":"Guorong Zhang,&nbsp;Yuzhong Wang,&nbsp;Nobuhiro Yuki","doi":"10.1111/jns.70147","DOIUrl":"10.1111/jns.70147","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Guillain–Barré syndrome (GBS) typically presents with symmetric weakness, but marked asymmetry can mimic stroke and delay diagnosis, especially when unilateral onset progresses to bilateral asymmetric involvement. We aimed to characterize this phenotype and identify features that facilitate early recognition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively analyzed 611 consecutive patients with GBS over 10 years. Asymmetry was defined as a difference of ≥ 2 points on the Medical Research Council (MRC) scale between contralateral limbs. Clinical features, electrophysiological subtypes, and diagnostic timelines were compared between asymmetric and symmetric cases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Thirty-two patients (5.2%) exhibited asymmetric onset. Compared with symmetric cases, asymmetric GBS had fewer antecedent respiratory infections (12.5% vs. 32.1%; <i>p</i> = 0.02) and no facial weakness (0% vs. 13.6%; <i>p</i> = 0.049). Twenty-two patients progressed to symmetric weakness; among 10 patients with persistent asymmetry, 6 unilateral onset cases evolved into bilateral asymmetric involvement, all initially misdiagnosed as stroke. Of these 10, 6 (60%) lacked sensory involvement, 7 (70%) had axonal GBS, and 4/7 (57%) were anti-ganglioside antibody positive. Asymmetric GBS was associated with longer diagnostic delays (median 3 vs. 2 days; <i>p</i> &lt; 0.001), longer admission-to-immunotherapy intervals (median 4 vs. 3 days; <i>p</i> &lt; 0.001), and greater disability at nadir (median 4 vs. 3; <i>p</i> = 0.01).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Within asymmetric GBS, unilateral-onset cases that evolve into bilateral asymmetric involvement are the subgroup most likely to mimic stroke. The absence of facial weakness, few antecedent respiratory infections, axonal electrophysiologic subtype, and positive anti-ganglioside antibodies may aid recognition and timely immunotherapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"31 3","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148447377","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}