Journal of neuroimmunology最新文献

{"title":"Clinico-pathological correlation in unilateral cortical encephalitis treated with tocilizumab after first-line treatment failure","authors":"Samir Alkabie ,&nbsp;Samer Ali ,&nbsp;Saeed Asiry ,&nbsp;Ana M. Franceschi ,&nbsp;Derek Chong ,&nbsp;Souhel Najjar","doi":"10.1016/j.jneuroim.2025.578764","DOIUrl":"10.1016/j.jneuroim.2025.578764","url":null,"abstract":"<div><h3>Objectives</h3><div>To characterize clinico-pathologic findings and therapeutic response in a rare case of unilateral cortical encephalitis successfully treated with tocilizumab after first-line treatment failure, highlighting potential immune mechanisms.</div></div><div><h3>Methods</h3><div>Case report.</div></div><div><h3>Results</h3><div>A 49-year-old man developed fever, seizure, and hemicortical deficits. MRI showed right cortical T2-hyperintensity, gyral enhancement, corresponding to ¹⁸F-FDG-PET hypermetabolism, compatible with unilateral cortical encephalitis. Extensive metabolic, infectious, and malignancy workup was unrevealing. Neural autoantibodies were negative. 6-months of progressive cognitive decline, visual, speech, and gait disturbance and an infectious event (appendicitis) preceded acute unihemispheric encephalitic syndrome. Brain biopsy demonstrated increased cortical perineuronal microglial activation, retraction of astrocytic processes from microvessels suggestive of blood-brain barrier disruption, and mainly perivascular CD4⁺T-cell infiltrates, alongside excess circulating interleukin-18 collectively implicating innate and adaptive immune mechanisms. Initial treatment with pulse steroids and intravenous immunoglobulin failed to yield improvement. Tocilizumab as second-line treatment concomitant to weekly pulse steroids led to significant recovery in cognition, gaze deviation, speech, and gait and resolution of imaging abnormalities.</div></div><div><h3>Discussion</h3><div>Tocilizumab—an IL-6 receptor blocker—was selected given the pleiotropic role of IL-6 in proinflammatory CD4⁺T-cell differentiation (Th17/Treg imbalance) and innate immune-driven CNS inflammation. This case illustrates the utility of clinico-pathological correlation and cytokine profiling in guiding immunotherapy selection in antibody-negative autoimmune encephalitis.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578764"},"PeriodicalIF":2.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epstein-Barr virus reactivation is associated with altered immune cell profiles in peripheral blood and cerebrospinal fluid of treatment-naive multiple sclerosis patients","authors":"Vasileios Gouzouasis ,&nbsp;Margaritis Tsifintaris ,&nbsp;Spyros Tastsoglou ,&nbsp;Nikos Markoglou ,&nbsp;Dimitris Karathanasis ,&nbsp;Lila Dimitrakopoulou ,&nbsp;Anastasia Dagkonaki ,&nbsp;Evangelos Korakidis ,&nbsp;George Mpekoulis ,&nbsp;Niki Vassilaki ,&nbsp;Artemis G. Hatzigeorgiou ,&nbsp;Maria Anagnostouli ,&nbsp;Maria Eleftheria Evangelopoulos ,&nbsp;Antonis Giannakakis ,&nbsp;Lesley Probert ,&nbsp;Hellenic Academy of Neuroimmunology","doi":"10.1016/j.jneuroim.2025.578758","DOIUrl":"10.1016/j.jneuroim.2025.578758","url":null,"abstract":"<div><div>Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, with autoimmune and neurodegenerative components, recently linked with Epstein-Barr virus (EBV) infection. To investigate immunological alterations associated with EBV reactivation (EBV-R) in MS we analyzed immune cell profiles in matched peripheral blood (PB) and cerebrospinal fluid (CSF) samples from treatment-naive MS patients, in relation to plasma EBV serology markers. In our Hellenic MS cohort, 12 of 33 patients (39 %) exhibited serological evidence of EBV-R (VCA IgG+ with VCA IgA+, VCA IgM+, or EA(D) IgG+), and 7 of these 12 also tested positive for plasma <em>BZLF1</em> mRNA, indicative of lytic infection. EBV-R patients showed reduced CD19+ B cells in PB and equal proportions in CSF compared to patients with latent EBV infection. Conversely, EBV-R patients showed increased cytotoxic CD56^dim NK cells and CD14⁺ monocytes in PB, while cytotoxic CD56^dim NK cells remained absent in the CSF, regardless of EBV status. Proportions of regulatory CD56^bright NK cells were reduced in both PB and CSF during EBV-R. Our results reveal that MS patients with serological evidence of EBV-R show altered immune responses, with reduced B cell proportions in the PB in the presence of expanded cytotoxic NK cells, and unaffected B cell proportions in CSF in the absence of cytotoxic NK cell surveillance.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578758"},"PeriodicalIF":2.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-NMDAR encephalitis across the lifespan: Clinical, electrophysiological, and prognostic insights from a Latin American cohort","authors":"Mariano Marrodan ,&nbsp;Carolina I. Perez Arana ,&nbsp;Ricardo J. Kirchner ,&nbsp;Francisco J. Varela ,&nbsp;Gabriela I. Orzuza ,&nbsp;Angeles Schteinschnaider ,&nbsp;Miriam G. Chaderevian ,&nbsp;Cristina Vita ,&nbsp;Mauricio F. Farez ,&nbsp;Jorge Correale","doi":"10.1016/j.jneuroim.2025.578766","DOIUrl":"10.1016/j.jneuroim.2025.578766","url":null,"abstract":"<div><h3>Background and objectives</h3><div>Anti-N-Methyl-<span>d</span>-aspartate receptor encephalitis (NMDARE) is the most prevalent autoimmune encephalitis, primarily affecting young females. Its clinical heterogeneity, particularly in underrepresented populations, poses diagnostic and therapeutic challenges. Epidemiological data from Latin America remain limited. This study aimed to characterise the demographic, clinical, and neuroimaging features of NMDARE in Latin American tertiary centres, with a focus on age-related differences.</div></div><div><h3>Methods</h3><div>A retrospective cohort study included NMDARE cases between January 2016 and December 2024. Inclusion criteria required anti-NMDAR antibody positivity in CSF and/or serum. Demographic, clinical, and paraclinical data were systematically collected. Comparisons between paediatric (&lt;18 years) and adult (≥18 years) patients were conducted using appropriate statistical tests.</div></div><div><h3>Results</h3><div>Of 1026 screened patients, 58 tested positive for anti-NMDAR antibodies, and 49 met inclusion criteria. Female predominance was higher among adults (61.5 % vs. 30.4 %; <em>p</em> = 0.03). Adults more frequently presented with confusion (57.7 % vs. 13 %; <em>p</em> = 0.003), mood disturbances (61.5 % vs. 26.1 %; p = 0.03), cognitive impairment (76.9 % vs. 36.1 %; <em>p</em> = 0.001), and dysautonomia (19.2 % vs. 0 %; <em>p</em> = 0.04). Speech disturbances (56.5 % vs. 34.6 %; <em>p</em> = 0.02), movement disorders (56.5 % vs 34.6 %, <em>p</em> = 0.06), and EEG abnormalities (69.6 % vs. 42.3 %; <em>p</em> = 0.01) were more frequent in paediatric patients. CSF pleocytosis was independently associated with ICU admission (OR = 11, p = 0.01). Relapse occurred in 10 % of cases.</div></div><div><h3>Discussion</h3><div>In this Latin American cohort, NMDARE presents distinct age-dependent clinical profiles. While existing diagnostic criteria are broadly applicable, awareness of age-specific features—particularly psychiatric symptoms in adults and EEG abnormalities in children—may improve diagnostic accuracy and guide tailored management strategies. Larger cohort studies in other populations have reported different findings, underscoring the importance of regional studies and the need for additional research to validate and generalize these results.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578766"},"PeriodicalIF":2.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long non-coding RNA NEAT1 modulates microglial NLRP3 inflammasome activation","authors":"Bora Tastan ,&nbsp;Aysen Cotuk ,&nbsp;Burak I. Arioz ,&nbsp;Bilge Karacicek ,&nbsp;Beyza Ture ,&nbsp;Nilsu Tastan ,&nbsp;Sermin Genc","doi":"10.1016/j.jneuroim.2025.578770","DOIUrl":"10.1016/j.jneuroim.2025.578770","url":null,"abstract":"<div><div>Microglia, the resident macrophages in the central nervous system (CNS), play a fundamental role in maintaining CNS homeostasis and responding to immune challenges. Dysregulated microglial activation and subsequent neuroinflammation are associated with various CNS diseases. A key mechanism driving neuroinflammation is the activation of the NLRP3 inflammasome complex triggered by diverse molecular motifs. The microglial NLRP3 inflammasome activation has been implicated in a plethora of diseases, including cardiovascular, autoimmune, and neurodegenerative diseases. Long non-coding RNAs (lncRNAs), particularly Nuclear Enriched Abundant Transcript 1 (NEAT1), have emerged as essential players in gene regulation and inflammation. In this study, we investigated the role of NEAT1 in microglial NLRP3 inflammasome activation utilizing <em>in vitro</em> and <em>in vivo</em> models. Our <em>in vivo</em> studies showed that NEAT1 knockout alleviates NLRP3 inflammasome activation in LPS-injected NEAT1 KO mice. Additionally, our <em>in vitro</em> studies confirmed these findings, demonstrating that NEAT1 expression is upregulated upon NLRP3 inflammasome activation in microglia. Further experiments revealed that NEAT1 depletion with siRNA significantly attenuated NLRP3 inflammasome activation and the release of pro-inflammatory cytokine IL-1β. Mechanistically, we found that NEAT1 interacted with RNA-binding proteins to regulate NLRP3 inflammasome activation. Given the central role of microglial NLRP3 inflammasome activation in neuroinflammation, our findings elaborated the regulatory mechanisms involving NEAT1, thus offering potential therapeutic avenues for CNS disorders.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578770"},"PeriodicalIF":2.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145227060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in the neuroimmune response following heavy, binge-like alcohol exposure in adolescent rats","authors":"Catherine E. Van Doorn ,&nbsp;Natalie Nawarawong ,&nbsp;Deann M. Hopkins ,&nbsp;Hui Peng ,&nbsp;James R. Pauly ,&nbsp;Kimberly Nixon","doi":"10.1016/j.jneuroim.2025.578742","DOIUrl":"10.1016/j.jneuroim.2025.578742","url":null,"abstract":"<div><div>Adolescents who consume alcohol show a high prevalence of binge drinking, which has been linked to brain damage and neuroimmune reactions that increase risk for developing an alcohol use disorder (AUD). Adolescent female drinking patterns have surpassed males, yet little is known about damaging effects of alcohol in females. Known sex differences in neuroimmune reactivity, specifically microglial reactivity, suggest that the female brain will differ from males. Therefore, we examined indicators of neuroimmune activation and neurodegeneration following 2 days of heavy, bingelike exposure in adolescent male and female rats. Translocator protein 18kD (TSPO) expression assessed by [³H]PK-11195 autoradiography revealed that adolescent female rats showed a brief and immediate response in the thalamus, while male rats showed a delayed and sustained increase in the thalamus and hippocampus versus same-sex controls. Neurodegeneration assessed by Fluoro-Jade-B (FJB) dye showed that alcohol-induced cell death was modest for both sexes. Males showed cell death in the entorhinal cortex while females showed greater cell death in the perirhinal and piriform cortices. Additional neuroimmune measures of pro-inflammatory cytokine, IL-6, was decreased in the hippocampus and entorhinal cortex a week after alcohol exposure in females only. No changes in brain-derived neurotrophic factor (BDNF) were found in either sex or region. Overall, these experiments show adolescent females and males display unique neuroimmune responses and neurodegeneration profiles following heavy binge-like exposure. These data imply that females show a impaired neuroimmune response to alcohol that could contribute to sex differences in damage and deficits caused by alcohol.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578742"},"PeriodicalIF":2.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145005085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The hidden toll: Atrophy of key central nervous system relays in African American women with multiple sclerosis","authors":"Nabeela Nathoo ,&nbsp;Nur Neyal ,&nbsp;Jiye Son ,&nbsp;Christopher G. Schwarz ,&nbsp;Elizabeth J. Atkinson ,&nbsp;Holly A. Morrison ,&nbsp;June Kendall Thomas ,&nbsp;John D. Port ,&nbsp;Kejal Kantarci ,&nbsp;Orhun H. Kantarci ,&nbsp;Burcu Zeydan","doi":"10.1016/j.jneuroim.2025.578776","DOIUrl":"10.1016/j.jneuroim.2025.578776","url":null,"abstract":"<div><h3>Background</h3><div>African American persons with MS (AApwMS) have more aggressive clinical and imaging outcomes than White American pwMS (WApwMS), including lower brain and spinal cord (SC) volumes. However, imaging studies are lacking considering the effects of sex, race, and ethnicity together.</div></div><div><h3>Objective</h3><div>Compare MS clinical and imaging features among AApwMS and WApwMS, incorporating the modifying effects of sex, race, and ethnicity.</div></div><div><h3>Methods</h3><div>Clinical variables and MRI were obtained for AApwMS and WApwMS.</div></div><div><h3>Results</h3><div>Thirty-five MRIs in 28 AApwMS (61 % female) and 255 MRIs in 91 WApwMS (68 % female) were evaluated. AApwMS had a shorter MS disease duration (median 5.9 years, IQR 2.7–13.1) compared to WApwMS (9.4 years, IQR 3.8–17.0; <em>p</em> = 0.034). Fewer AApwMS ever used disease modifying therapy (69 %) compared to WApwMS (92 %; <em>p</em> &lt; 0.001), while the likelihood of having progressive MS and developing severe disability were similar between groups (<em>p</em> &gt; 0.05). AA women with MS had smaller thalamus (<em>p</em> = 0.016), cerebellar grey matter (<em>p</em> = 0.025), and SC-C2 (<em>p</em> = 0.005) volumes than WA women with MS. Although multiple brain and SC regions were smaller in AA men than WA men with MS, the differences were not significant.</div></div><div><h3>Conclusion</h3><div>Interaction between sex, race, and ethnicity may influence differences in imaging metrics of key central nervous system relays, likely preceding clinical worsening in MS.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578776"},"PeriodicalIF":2.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145267110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Translational Evidence of Immunomodulation by Addictive Drugs: Mechanisms and Therapeutic Targets","authors":"Luis M. Tuesta ,&nbsp;Cassandra D. Gipson","doi":"10.1016/j.jneuroim.2025.578762","DOIUrl":"10.1016/j.jneuroim.2025.578762","url":null,"abstract":"","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578762"},"PeriodicalIF":2.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of autophagy in chronic pain","authors":"Fu-qi Zhu ,&nbsp;Wen-jun Zhang ,&nbsp;Bao-zhu Guan","doi":"10.1016/j.jneuroim.2025.578757","DOIUrl":"10.1016/j.jneuroim.2025.578757","url":null,"abstract":"<div><div>Pain is the biggest factor affecting patients' daily life, and how to alleviate patients' pain and prevent it from developing into chronic pain has always been a key therapeutic goal for clinicians. There are three main causes of chronic pain, which are inflammation, nerve and tumor. And autophagy, as an important pathway to maintain homeostasis of the organism, not only affects the normal autophagy function, but also plays an important role in anti-inflammation, maintenance of nerve cell homeostasis, and inhibition of cancer occurrence and metastasis. Based on the above characteristics, we believe that autophagy has great potential in reducing and avoiding chronic pain. In this paper, after introducing chronic pain and autophagy-related genes, we delve into the pathological mechanisms of chronic pain generation, search for the relationship between autophagy and the three major causes of chronic pain, and find that autophagy may have a powerful therapeutic effect in reducing pain. We believe that autophagy can be a new target for the treatment of chronic pain.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578757"},"PeriodicalIF":2.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Over-excitation of tyrosine hydroxylase neurons in the paraventricular nucleus of the hypothalamus drives a neuroimmune positive feedback loop in rheumatoid arthritis","authors":"Hongxin Li ,&nbsp;Hongli Yu ,&nbsp;Xiuzhi Zhao ,&nbsp;Jiaxin Xu","doi":"10.1016/j.jneuroim.2025.578773","DOIUrl":"10.1016/j.jneuroim.2025.578773","url":null,"abstract":"<div><h3>Background</h3><div>Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and pain, leading to a significant decline in patients' quality of life. Recent studies suggest that the central nervous system (CNS) may also contribute to disease progression by modulating autonomic and immune functions. However, the precise mechanisms underlying CNS involvement remain unclear.</div></div><div><h3>Objective</h3><div>This study aims to investigate the alterations in the functional state of tyrosine hydroxylase (TH) within the paraventricular nucleus (PVN) in RA and to explore their potential role in regulating peripheral immune responses.</div></div><div><h3>Methods</h3><div>An adjuvant-induced arthritis (AA) mouse model was employed. Changes in PVN-TH neuron excitability were assessed using double immunofluorescence staining, whole-cell patch-clamp recording, and in vivo calcium imaging. Chemogenetic inhibition of PVN-TH neurons was performed to evaluate behavioral manifestations of RA, such as paw swelling, paw withdrawal latency, and joint scoring, as well as the concentration of NE released from sympathetic nerve endings in the popliteal lymph nodes and subsequent immune responses in the popliteal lymph nodes, including T cell proliferation and dendritic cell activation.</div></div><div><h3>Results</h3><div>AA mice displayed pronounced hyperactivity of PVN-TH neurons, as indicated by increased c-Fos⁺ expression, higher action potential firing frequency, and elevated calcium signal amplitudes. Targeted inhibition of these neurons significantly reduced inflammatory symptoms and the concentration of NE released from sympathetic nerve endings in the popliteal lymph nodes, and decreased T cell proliferation and dendritic cell activation in the popliteal lymph nodes.</div></div><div><h3>Conclusion</h3><div>In the RA model, pathological hyperactivity exhibited by PVN-TH neurons may be involved in peripheral immune regulation through central sensitization and inflammatory signaling. These neurons may be key hubs driven by the central nervous system, providing new insights into neuroimmune mechanisms and potential targets for neuroimmunotherapy in RA.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578773"},"PeriodicalIF":2.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145267111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corneal neuro-immune crosstalk in Fabry disease: An in vivo confocal microscopic study","authors":"Xuecong Zhou ,&nbsp;Yingsi Li ,&nbsp;Yawen Zhao ,&nbsp;Xiaoming Yan ,&nbsp;Wei Zhang ,&nbsp;Yuan Wu","doi":"10.1016/j.jneuroim.2025.578759","DOIUrl":"10.1016/j.jneuroim.2025.578759","url":null,"abstract":"<div><h3>Purpose</h3><div>This study aims to assess the corneal nerve damage and corneal immune alteration by <em>in vivo</em> confocal microscopy (IVCM) in Fabry disease (FD)</div></div><div><h3>Methods</h3><div>Sixty-two eyes from 31 patients with FD were analysed and compared with fifty eyes from 25 healthy controls in this prospective, cross-sectional, controlled, single-center study. After evaluating corneal sensation by the Cochet-bonnet esthesiometer, the IVCM was performed to evaluate the sub-basal nerve plexus (CSNP) including density, number, tortuosity and reflectivity of corneal nerve, and the inflammatory cells including mature/immature Langerhans cells (LCs) and leukocytes. The differences between FD and healthy controls, different genders (heterozygous and hemizygous), phenotypes (classical, nonclassical) and Mainz severity score index (MSSI) scores were compared</div></div><div><h3>Results</h3><div>A significant reduction of corneal nerve density, number and reflectivity, as well as an increase of tortuosity occurred in the FD group compared with healthy controls (<em>P</em> &lt; 0.001). The density of LCs was significantly increased in the FD group compared with the healthy controls in the central cornea (<em>P</em> = 0.016) and peripheral cornea (<em>P</em> &lt; 0.001). The more severe corneal neuropathy and higher density of LCs were found in hemizygous males than heterozygous females (<em>P</em> &lt; 0.05). As for the difference between distinct phenotypes and MSSI scores, we did not find significant difference in corneal nerve parameters and LCs density</div></div><div><h3>Conclusions</h3><div>IVCM provides parameters that reliably indicate corneal nerve damage and inflammatory activation in patients with FD</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578759"},"PeriodicalIF":2.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145118971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}