Journal of the Peripheral Nervous System最新文献

{"title":"Altered Cellular Pathways in the Blood of Patients With Guillain-Barre Syndrome","authors":"Marília Fabiana de Oliveira Lima,&nbsp;Viviane Brito Nogueira,&nbsp;Wendy Maury,&nbsp;Mary Edythe Wilson,&nbsp;Mário Emílio Teixeira Dourado Júnior,&nbsp;Diego Gomes Teixeira,&nbsp;Selma Maria Bezerra Jeronimo","doi":"10.1111/jns.70012","DOIUrl":"https://doi.org/10.1111/jns.70012","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 disorder, with a global incidence ranging from 1 to 2 individuals per 100,000 people/year. Infections and vaccines have been implicated as causes triggering GBS. The aim of the study was to identify host genes involved in the pathogenesis of GBS when Zika (ZIKV) and Chikungunya viruses (CHIKV) were introduced in Brazil.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A case–control study of GBS was performed when ZIKV and CHIKV were introduced into a naïve population. GBS was studied during both acute and postacute phases. RNA sequencing was conducted using whole blood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>GBS typically manifested a week after rash and fever; acute inflammatory demyelinating polyradiculoneuropathy was more frequent. None of the GBS cases had a poor outcome. Serological assays for ZIKV and CHIKV revealed high titers of immunoglobulin G for both viruses in 9 out of 11 subjects. Metatranscriptomic analyses unveiled an increased abundance of reads attributed to <i>Pseudomonas tolaasii</i> and <i>Toxoplasma gondii</i> in the acute phase. Analysis of differentially expressed host genes during the acute phase revealed altered expression of genes associated with axogenesis, synapse assembly, and presynapse organization. Moreover, genes upregulated during acute GBS were primarily related to inflammation and the inflammasome pathways, including AIM2, NLR family genes and LRR-protein genes, and IL-10.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>These findings suggest that inflammasome activation via AIM2 could play a role in tissue damage during GBS. Further investigation into the general activation of innate inflammatory responses is warranted to elucidate their potential contribution to the pathology of GBS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"30 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638835","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":"Feasibility and Reliability of a Monitoring App for Chronic Inflammatory Neuropathies","authors":"Doreen L. Lemmen,&nbsp;Ruben P. A. van Eijk,&nbsp;Jordi W. J. van Unnik,&nbsp;Jeffrey A. Allen,&nbsp;Yusuf A. Rajabally,&nbsp;Leonard H. van den Berg,&nbsp;W. Ludo van der Pol,&nbsp;H. Stephan Goedee","doi":"10.1111/jns.70005","DOIUrl":"https://doi.org/10.1111/jns.70005","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Multifocal motor neuropathy (MMN) and chronic inflammatory demyelinating polyneuropathy (CIDP) are immune-mediated neuropathies characterized by muscle weakness and/or sensory deficits. Identifying treatment response, relapse, and stability can be challenging in these chronic, sometimes unpredictable, conditions. This study explores the potential of a monitoring app designed to address these challenges.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients were monitored weekly or monthly, based on stability and patient preference, using grip strength, modified timed-up-and go (mTUG), and patient-reported outcome measures (PROMs). User experience was evaluated via a questionnaire addressing content and ease of use (scale 0–10). Adherence was measured as the percentage of completed mandatory assessments. We investigated reliability using intra-class correlation coefficients (ICCs) and standard errors of the mean (SEM) of repeated measurements. Longitudinal changes were analyzed using linear mixed-effects models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We included 38 patients, with a mean follow-up of 11 months (IQR 4.6–19.5). The mean user experience score was 8.35/10 (range 7–10). Adherence was 93% (95% CI: 91.9%–94.1%). Reported remote measurements for grip strength were 1358/1468 (93%), and 1343/1430 (94%) for mTUG. Grip strength and mTUG ICCs were both 0.96 (95% CI: 0.93–0.98 and 0.92–0.99, respectively). The average SEM was 8.46% (95% CI: 6.58–10.28) for grip strength and 8.18% (95% CI: 6.12–10.41) for mTUG. Only grip strength changed significantly, increasing by 3.1 pounds per 6 months (95% CI: 0.61–5.83; <i>p</i> = 0.016).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Our study demonstrates that tele-neuromonitoring is feasible and reliable, showing high adherence, positive user experience and high ICCs. We anticipate tele-neuromonitoring could complement routine follow-up, enabling clinicians to make better-informed treatment decisions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"30 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.70005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638767","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":"Paraneoplastic Leucine Zipper 4 IgG Associated Motor-Predominant Polyradiculoneuropathy","authors":"Alex Panrudkevich,&nbsp;Duaa Jabari,&nbsp;Brendan Putko,&nbsp;Catherine Daley,&nbsp;Richard A. Lewis,&nbsp;Divyanshu Dubey,&nbsp;Marcus V. Pinto","doi":"10.1111/jns.70013","DOIUrl":"https://doi.org/10.1111/jns.70013","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Leucine Zipper 4 (LUZP4)-immunoglobulin G (IgG) is a novel antibody implicated in germ cell tumor-related paraneoplastic neurologic syndrome. We report a case of painful, progressive tetraparesis associated with testicular seminoma and LUZP4-IgG seropositivity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case Report</h3>\u0000 \u0000 <p>A 51-year-old male presented with a 5-week history of lower limb predominant progressive weakness. Nerve conduction studies (NCS) and electromyography (EMG) revealed a subacute axonal polyradiculoneuropathy. MRI lumbar spine showed thickening of the cauda equina and enhancement of the lower thoracic spinal cord/conus. Cerebrospinal fluid (CSF) showed a lymphocytic pleocytosis, three oligoclonal bands, and mildly elevated protein. Initial treatment with intravenous immunoglobulin (IVIG) and prednisone produced temporary improvement. CT targeted retroperitoneal lymph node biopsy revealed a seminoma, which was treated with orchiectomy and chemotherapy. The testicular tissue was consistent with a regressed germ cell tumor. His course was subsequently refractory to IVIG, prednisone, and plasma exchange. LUZP4 antibodies were detected in serum, prompting treatment with cyclophosphamide and prednisone. At the 4-month follow-up, the patient had significant improvement in hand strength and had transitioned from walker to cane.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>LUZP4-IgG seropositivity and identification of retroperitoneal seminoma confirmed a paraneoplastic neurologic syndrome, which is a CD8+ T-cell-mediated disorder. Aggressive immunotherapy was initiated, resulting in clinical improvement. This case underscores the importance of identifying specific serologic biomarkers that can inform therapeutic decisions and improve outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"30 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638769","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":"Loss of MEGF10 Decreases the Number of Perisynaptic Schwann Cells and Innervation of Neuromuscular Junctions in Aging Mice","authors":"Devin Juros,&nbsp;Robert Louis Hastings,&nbsp;Ariane Pendragon,&nbsp;Jeremy Kay,&nbsp;Gregorio Valdez","doi":"10.1111/jns.70014","DOIUrl":"https://doi.org/10.1111/jns.70014","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>At the neuromuscular junction (NMJ), the synapse between motor neurons and muscle fibers, reside perisynaptic Schwann cells (PSCs) which are specialized glia that regulate the maintenance and repair of this synapse. While we know how PSC morphology and numbers change in aging and various neuromuscular disorders that adversely affect the NMJ, the molecular mechanisms that alter PSC functions remain unknown. In this study, we investigated whether MEGF10 in PSCs modulates NMJ stability in developing, healthy young adult, middle-aged, and axotomized mice. MEGF10 is a glial phagocytic receptor that is enriched in PSCs compared to other Schwann cells (SCs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We isolated PSCs from a transgenic reporter mouse line to assess <i>Megf10</i> expression at different ages and following nerve injury using qPCR. We then used a conditional mouse lacking <i>Megf10</i> in all SCs, including PSCs (<i>Megf10</i> SC-KO mice). We examined NMJs and axonal debris clearance in <i>Megf10</i> SC-KO mice using confocal microscopy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that <i>Megf10</i> expression in PSCs peaks during development and decreases during aging and following denervation of NMJs. NMJs were morphologically normal in developing and young adult <i>Megf10</i> SC-KO mice. This was not the case in middle-aged <i>Megf10</i> SC-KO mice, in which NMJs presented with fewer PSCs, decreased PSC coverage of the endplate, and decreased innervation in comparison to control mice. Following nerve injury-induced damage, axonal debris at the NMJ was cleared faster in <i>Megf10</i> SC-KO mice; yet, the rate of reinnervation was unchanged compared to control mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>The data in this study suggest that MEGF10 in PSCs functions to maintain PSC number and NMJ innervation during aging. This study also suggests important roles for MEGF10 in mediating the clearance of axonal debris at NMJs following nerve injury.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"30 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638768","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":"Dapagliflozin for Small Nerve Fibre Regeneration in Diabetic Peripheral Neuropathy: A Randomised Controlled Study (DINE)","authors":"Umanath Adhikari,&nbsp;Hoda Gad,&nbsp;Debajyoti Chatterjee,&nbsp;Chintan Malhotra,&nbsp;Sanjay Kumar Bhadada,&nbsp;Rayaz A. Malik,&nbsp;Ashu Rastogi","doi":"10.1111/jns.70011","DOIUrl":"https://doi.org/10.1111/jns.70011","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>There are currently no FDA-approved disease-modifying therapies for diabetic peripheral neuropathy (DPN). We evaluated the effect of the sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin in Type 2 diabetes mellitus (T2DM) with DPN.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Research Design and Methods</h3>\u0000 \u0000 <p>In this prospective, open-label, randomised, controlled study, 40 participants with DPN were randomised to receive add-on 10 mg dapagliflozin OD (Group A) to existing oral antidiabetic drugs (OAD) (<i>n</i> = 22) or continue OADs as a standard of care (Group B) (<i>n</i> = 18). Participants underwent assessment of neuropathic symptoms and signs (MNSI), vibration perception threshold (VPT), corneal confocal microscopy (CCM) to quantify corneal nerve fibre density (CNFD), corneal nerve branch density (CNBD) and corneal nerve fibre length (CNFL) and skin biopsy to assess intraepidermal nerve fibre density (IENFD) and plasma markers of oxidative stress at randomisation and after 6 months.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>HbA1c decreased in Group A (<i>p</i> = 0.002) and Group B (<i>p</i> = 0.003), with no change in weight, body mass index (BMI) or lipids. Total MNSI increased in Group A (<i>p</i> = 0.01) with no change in Group B (<i>p</i> = 0.06). IENFD increased significantly in Group A (<i>p</i> = 0.01) and Group B (<i>p</i> = 0.01), while CNFD (<i>p</i> = 0.002), CNBD (<i>p</i> &lt; 0.001) and CNFL (<i>p</i> = 0.025) increased in Group A with no change in Group B. There was a significant increase in glutathione peroxidase (<i>p</i> = 0.02) in Group A with no change in Group B, and a decrease in malondialdehyde in both groups (<i>p</i> &lt; 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In participants with T2DM and DPN, dapagliflozin was associated with small nerve fibre regeneration and improvement in markers of oxidative stress.</p>\u0000 \u0000 <p><b>Trial Registration:</b> Clinical Trial Registry India, CRTI Reg. No (CTRI/2022/06/043236); ClinicalTrials.gov Identifier: NCT05162690</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"30 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554722","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":"Cytokine Signature Unveils Subgroups of Patients With Immune-Mediated Sensory Neuronopathies","authors":"Christian P. Moritz,&nbsp;Yannick Tholance,&nbsp;Coralie Borowczyk,&nbsp;Fabienne Jospin,&nbsp;Stéphane Paul,&nbsp;Jean-Christophe Antoine,&nbsp;Jean-Philippe Camdessanché","doi":"10.1111/jns.70008","DOIUrl":"https://doi.org/10.1111/jns.70008","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Immune-mediated sensory neuronopathies (SNN) can occur alongside autoimmune disorders (e.g., Sjögren syndrome), involve autoantibodies (such as anti-FGFR3 or anti-AGO antibodies), or present in isolation. The underlying mechanisms remain unclear. This study aimed to investigate the role of proinflammatory cytokines in these conditions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Blood levels of IL-1β, IL-6, IL-17, TNF-α, INF α-2, and INF-γ were measured using a Bioplex T200 platform and the Bio-Plex Pro Reagent Kit III in 113 patients with SNN between 2.4 and 464.4 months after symptom onset, categorized based on disease course (acute, subacute, chronic). Eighteen patients had anti-AGO antibodies, 48 had anti-FGFR3 antibodies, and 14 had an autoimmune disease without detectable anti-AGO or FGFR3 antibodies. Disease extent was measured by the SNN score, while the disease severity was evaluated using the modified Rankin score. Immunoreactivity against IL-6 and INF-γ was measured via ELISA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Multicomponent analysis utilizing cytokines levels identified four distinct patient subgroups characterized by differences in age at onset and SNN score. No significant differences were observed among the subgroups regarding disease course and severity, presence of anti-AGO or anti-FGFR3 antibodies, or association with an autoimmune disease. A small subgroup of three younger patients exhibited the highest levels of TNF-α, IL-6, and IL-1β. Another subgroup of seven patients displayed elevated INF α-2 levels and tended towards highest SNN scores. The largest group (95 subjects) comprised older individuals with relatively lower cytokine levels and decreased anti-IL-6 immunoreactivity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>These cytokine profiles suggest diverse underlying mechanisms within immune-mediated SNN. Further investigation is warranted to determine whether certain profiles, particularly those involving young patients with elevated proinflammatory cytokines, might benefit from targeted treatments.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"30 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.70008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554662","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":"Eculizumab as a Disease-Modifying Therapy in Chronic Inflammatory Demyelinating Polyneuropathy (CIDP): A Case Report","authors":"Edoardo Dalmato Schilke,&nbsp;Diletta Cereda,&nbsp;Maria Letizia Fusco,&nbsp;Lorenzo Stanzani,&nbsp;Laura Marzorati,&nbsp;Michela Ripolone,&nbsp;Letizia Bertolasi,&nbsp;Maura Frigo,&nbsp;Franco Molteni,&nbsp;Nico Farina,&nbsp;Carlo Ferrarese,&nbsp;Guido Cavaletti,&nbsp;Claudia Balducci","doi":"10.1111/jns.70010","DOIUrl":"https://doi.org/10.1111/jns.70010","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare immune-mediated disorder; about 20%–30% of patients do not adequately respond to first-line treatments (immunoglobulins, therapeutic plasmapheresis, and corticosteroids) posing diagnostic and therapeutic challenges.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case Report</h3>\u0000 \u0000 <p>We report the case of a 58-year-old man diagnosed with CIDP. During follow-up, he progressively became refractory to all first-line treatments. Therefore, 20 months after the diagnosis, an add-on therapy with Rituximab was tried. Despite previous works supporting the use of Rituximab in refractory CIDP, in our case, the patient experienced relapses and progressive increases in disability. After the exclusion of potential CIDP mimics and considering the histological findings that showed complement activation, we opted for an innovative therapeutic approach with Eculizumab that granted a significant clinical and neurophysiological benefit that persists after 7 months of follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>CIDP pathogenesis is characterized by a complex interplay of different immunopathological mechanisms, and the complement system may play a major role. The present case supports the role of complement-dependent toxicity in CIDP and suggests that complement-targeted therapies may represent a well-tolerated and effective alternative for CIDP treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"30 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.70010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143530055","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":"Results From a Phase 1 Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of ANX005, a C1q Inhibitor, in Patients With Guillain–Barré Syndrome","authors":"Quazi Deen Mohammad,&nbsp;Zhahirul Islam,&nbsp;Nowshin Papri,&nbsp;Shoma Hayat,&nbsp;Israt Jahan,&nbsp;Khan Abul Kalam Azad,&nbsp;Dean R. Artis,&nbsp;Benjamin Hoehn,&nbsp;Eric Humphriss,&nbsp;Ping Lin,&nbsp;Ted Yednock,&nbsp;Henk-André Kroon","doi":"10.1111/jns.70009","DOIUrl":"https://doi.org/10.1111/jns.70009","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Guillain–Barré syndrome (GBS) is an acute autoimmune peripheral neuropathy driven by autoantibodies and classical complement pathway activation. Despite treatments with intravenous immunoglobulin or plasma exchange, GBS remains characterized by variability in recovery and high incidence of residual disabilities. This randomized, double-blind, placebo-controlled Phase 1 trial evaluated the safety, tolerability, and pharmacokinetics of ANX005, a novel therapeutic targeting the classical complement cascade.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients with recent-onset GBS, who had no access to intravenous immunoglobulin or plasma exchange, received escalating doses of ANX005 or placebo as a single IV infusion. Primary objectives included assessments of safety. Secondary objectives included determination of pharmacokinetic and pharmacodynamic profiles and clinical outcomes through Week 8. Exploratory objectives included an evaluation of serum and cerebrospinal fluid (CSF) complement and tissue damage biomarkers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fifty patients were randomized to receive either ANX005 (<i>n</i> = 38) or placebo (<i>n</i> = 12). ANX005 was well-tolerated across all doses with no dose-limiting toxicities, suggesting an acceptable safety profile. Pharmacodynamic data showed effective C1q inhibition and a reduction in neurofilament light chain levels, suggesting nerve damage mitigation. Exploratory endpoints evaluating clinical outcomes included improvements in Medical Research Council sum scores, GBS-Disability Score, and Overall Neuropathy Limitations Scale with ANX005 compared to placebo, particularly in patients receiving doses that inhibited serum C1q for ≥ 1 week and provided C1q blockade in the CSF.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>These results support ANX005 as a targeted therapy for GBS that modulates the classical complement pathway. Further investigation in a larger Phase 3 trial is warranted to confirm these results and assess the long-term benefits of complement inhibition in patients with GBS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"30 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143489647","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":"Safety and Cost Analysis of Immunoglobulin Cessation Trials in Chronic Inflammatory Demyelinating Polyradiculoneuropathy","authors":"Shiwen Koay,&nbsp;Yi-Chun Chen,&nbsp;George Ransley,&nbsp;Laura Compton,&nbsp;Michael P. Lunn,&nbsp;Aisling S. Carr","doi":"10.1111/jns.70007","DOIUrl":"https://doi.org/10.1111/jns.70007","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is the most common chronic autoimmune neuropathy worldwide. A significant proportion of CIDP patients enter spontaneous or medication-related remission, remaining stable without immunotherapy. Overtreatment of CIDP has clinical and financial implications. We examined performance of IVIg cessation trials in our CIDP cohort and report safety and cost analysis outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In individuals with CIDP on maintenance IVIg treatment, a cessation trial was proposed in clinically stable patients with a static IVIg regimen over a 12-month period. We explored the proportion who were stable off treatment for 12 or more months and the time to recovery in those who declined and were re-treated. We examined cost implications of this approach.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>45/125 individuals met criteria for clinical stability, with median age 58 years, I-RODS 37/48, MRC-SS 69/70 and annual treatment costs £107 000/person. Nine individuals had cessation trials resulting in decline within 2 years prior and were not re-challenged, leaving 36 eligible individuals. 12 of 36 (33.3%) consented to cessation trial and eight of those (66.7%) remained stable off treatment for ≥ 12 months. The successful cessation trials resulted in a cost saving of £855 000/year, with a potential further saving of £1.7 million/year if all the eligible individuals had consented. All patients who deteriorated were rescued to previous baseline on retreatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Individuals with CIDP should be counselled about the natural history of the disease and future scheduled, targeted cessation trials. A dedicated clinical infrastructure is vital to safely perform cessation trials.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"30 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.70007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143438946","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":"Unique Nerve Tissue-Restricted T-Cell Clones in Chronic Inflammatory Demyelinating Polyneuropathy","authors":"G. G. A. van Lieverloo,&nbsp;D. C. Anang,&nbsp;M. E. Adrichem,&nbsp;B. A. Coert,&nbsp;A. E. Aronica,&nbsp;L. Wieske,&nbsp;I. N. van Schaik,&nbsp;N. de Vries,&nbsp;F. Eftimov","doi":"10.1111/jns.70006","DOIUrl":"https://doi.org/10.1111/jns.70006","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Chronic inflammatory demyelinating polyneuropathy (CIDP) is an immune-mediated disorder characterized by peripheral nerve damage. Although T lymphocytes (T-cells) are implicated in the pathogenesis of CIDP, we previously observed that the frequency of highly expanded T-cell clones (HECs) in peripheral blood of CIDP patients was not different from healthy controls. To investigate if local T-cells might be pathogenic, we employed next-generation sequencing to compare the TCRβ repertoire between peripheral blood and nerve tissue of CIDP patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Adaptive immune receptor repertoire sequencing (AIRR-Seq) of the TCRβ chain was conducted on peripheral blood and nerve tissue obtained from three newly diagnosed CIDP patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>All patients showed high numbers of highly expanded TCRβ clones in nerve tissue that were not detected or detected only in very low frequencies in blood, whereas in blood other HECs were found. Clustering analysis based on CDR3-similarity showed that these nerve tissue-restricted TCRβ clones were distinct from blood clones, as evidenced by the absence of prominent clusters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Unique nerve tissue-restricted TCRβ clones may indicate a highly localized immune response with localized expansion and/or retention of T-cells that could contribute to the pathomechanism of CIDP.</p>\u0000 \u0000 <p>Further characterization of the phenotype, antigen target and functionality of these T-cells is essential to determine their pathogenic role.</p>\u0000 </section>\u0000 </div>","PeriodicalId":17451,"journal":{"name":"Journal of the Peripheral Nervous System","volume":"30 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jns.70006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143438945","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}