Rheumatoid meningitis (RM) presents a diverse array of symptoms that can mimic stroke or transient ischemic attack (TIA), creating significant challenges for early clinical diagnosis.
Methods
This study reported on a patient who presented with recurrent stroke-like symptoms and was diagnosed with RM. Additionally, a literature review was conducted on PubMed using the terms “rheumatoid arthritis,” “central nervous system,” “meningitis,” and “rheumatoid meningitis” on December 20, 2023.
Results
Nineteen patients diagnosed with RM who exhibited stroke-like symptoms or TIA were included in the analysis. Of these, 58 % were male, with a median age of 65 years (range: 37–87 years). The duration of rheumatoid arthritis (RA) varied from 0 to 12 years. Approximately 80 % of patients showed meningeal enhancement on MRI, with 47 % displaying asymmetric enhancement, 21 % diffuse enhancement, and 5 % a mass-like lesion. CSF analysis revealed mild elevations in white blood cell count and protein in 68 % of patients. Biopsies were performed in 13 out of 19 cases, with 11 cases (85 %) showing chronic inflammation, including 10 with leptomeningitis or pachymeningitis, 1 with vasculitis, and 1 with necrotizing granulomatous meningitis. Corticosteroids were the most commonly used treatment.
Conclusion
For patients presenting with stroke-like or TIA symptoms who have a history of RA, it is crucial to consider RM in the differential diagnosis. Further research is needed to determine the most effective treatment strategies for these patients.
{"title":"Rheumatoid meningitis presented as recurrent stroke-like symptoms: A case report and literature review","authors":"Xin Yang , Shuping Fang , Zilong Hao , Weihong Kuang","doi":"10.1016/j.jneuroim.2025.578763","DOIUrl":"10.1016/j.jneuroim.2025.578763","url":null,"abstract":"<div><h3>Introduction</h3><div>Rheumatoid meningitis (RM) presents a diverse array of symptoms that can mimic stroke or transient ischemic attack (TIA), creating significant challenges for early clinical diagnosis.</div></div><div><h3>Methods</h3><div>This study reported on a patient who presented with recurrent stroke-like symptoms and was diagnosed with RM. Additionally, a literature review was conducted on PubMed using the terms “rheumatoid arthritis,” “central nervous system,” “meningitis,” and “rheumatoid meningitis” on December 20, 2023.</div></div><div><h3>Results</h3><div>Nineteen patients diagnosed with RM who exhibited stroke-like symptoms or TIA were included in the analysis. Of these, 58 % were male, with a median age of 65 years (range: 37–87 years). The duration of rheumatoid arthritis (RA) varied from 0 to 12 years. Approximately 80 % of patients showed meningeal enhancement on MRI, with 47 % displaying asymmetric enhancement, 21 % diffuse enhancement, and 5 % a mass-like lesion. CSF analysis revealed mild elevations in white blood cell count and protein in 68 % of patients. Biopsies were performed in 13 out of 19 cases, with 11 cases (85 %) showing chronic inflammation, including 10 with leptomeningitis or pachymeningitis, 1 with vasculitis, and 1 with necrotizing granulomatous meningitis. Corticosteroids were the most commonly used treatment.</div></div><div><h3>Conclusion</h3><div>For patients presenting with stroke-like or TIA symptoms who have a history of RA, it is crucial to consider RM in the differential diagnosis. Further research is needed to determine the most effective treatment strategies for these patients.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578763"},"PeriodicalIF":2.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154929","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}
Pub Date : 2025-09-23DOI: 10.1016/j.jneuroim.2025.578762
Luis M. Tuesta , Cassandra D. Gipson
{"title":"Translational Evidence of Immunomodulation by Addictive Drugs: Mechanisms and Therapeutic Targets","authors":"Luis M. Tuesta , 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":"2025-09-23","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}
Pub Date : 2025-09-21DOI: 10.1016/j.jneuroim.2025.578758
Vasileios Gouzouasis , Margaritis Tsifintaris , Spyros Tastsoglou , Nikos Markoglou , Dimitris Karathanasis , Lila Dimitrakopoulou , Anastasia Dagkonaki , Evangelos Korakidis , George Mpekoulis , Niki Vassilaki , Artemis G. Hatzigeorgiou , Maria Anagnostouli , Maria Eleftheria Evangelopoulos , Antonis Giannakakis , Lesley Probert , Hellenic Academy of Neuroimmunology
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 BZLF1 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 CD56dim NK cells and CD14+ monocytes in PB, while cytotoxic CD56dim NK cells remained absent in the CSF, regardless of EBV status. Proportions of regulatory CD56bright 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.
{"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 , Margaritis Tsifintaris , Spyros Tastsoglou , Nikos Markoglou , Dimitris Karathanasis , Lila Dimitrakopoulou , Anastasia Dagkonaki , Evangelos Korakidis , George Mpekoulis , Niki Vassilaki , Artemis G. Hatzigeorgiou , Maria Anagnostouli , Maria Eleftheria Evangelopoulos , Antonis Giannakakis , Lesley Probert , 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<sup>dim</sup> NK cells and CD14<sup>+</sup> monocytes in PB, while cytotoxic CD56<sup>dim</sup> NK cells remained absent in the CSF, regardless of EBV status. Proportions of regulatory CD56<sup>bright</sup> 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":"2025-09-21","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}
Pub Date : 2025-09-17DOI: 10.1016/j.jneuroim.2025.578760
Elisha Siwan , Asawin Tungpoomjaruswong , Vera Merheb , Fiona X.Z. Lee , Fakhria Kakar , Mark Acebes , Russell C Dale , David McDonald , Sudarshini Ramanathan , Ming-Wei Lin , David A Brown , Fabienne Brilot
MOG antibody-associated disease (MOGAD) diagnosis rests on seropositivity for MOG antibody (MOG-IgG). Live cell-based assays (CBA) are gold standards. Although flow cytometry live CBAs have high real-world sensitivity, their global implementation and diagnostic deployment have been challenged by perceptions of “in-house” design and custom optimization. Herein, we compared the analytical robustness of flow live MOG-IgG CBA across various cytometers in both research and diagnostic laboratories. Flow live CBAs were performed on three conventional (Fortessa, BDLSRII, Gallios), and two spectral cytometers (Aurora, ID7000). MOG-IgG titers were calculated by median fluorescence intensity (MFI), and intra- and inter assay precisions (CV%) and serostatuses were determined. The MFI detection range on Fortessa, currently used for testing, was significantly lower than spectral ID7000 (4.75-fold, p = 0.04) and Aurora (12-fold, p = 0.0001), albeit all MFIs correlated (p < 0.0001; R2 = 0.99). Interestingly, the high detection range was attributed to technology, not laboratory environments (p > 0.05). Intra- and inter-assay precisions were similar across cytometers. ID7000 and Fortessa had the lowest variation, with 4.6 % and 6.8 % intra-CV, respectively, and 15.7 % inter-CV. FACS ratio, currently reported as MOG-IgG titre, and MFIs were comparable and correlated for all cytometers (p < 0.001; R2 ≤ 0.99), regardless of the analysis software (p < 0.0001, R2 = 0.98). All serostatuses were highly concordant (κ = 1). Our results demonstrate that flow live CBAs can be validated in diagnostic laboratories across a range of flow cytometers with high reproducibility and repeatability. In particular, excellent assay performance on spectral flow cytometry strongly supports the proof-of-concept use of this technology for diagnostic purposes.
{"title":"Live MOG-IgG cell-based assay: Comparison across flow cytometers and diagnostic validation on high-sensitivity full spectrum flow cytometry","authors":"Elisha Siwan , Asawin Tungpoomjaruswong , Vera Merheb , Fiona X.Z. Lee , Fakhria Kakar , Mark Acebes , Russell C Dale , David McDonald , Sudarshini Ramanathan , Ming-Wei Lin , David A Brown , Fabienne Brilot","doi":"10.1016/j.jneuroim.2025.578760","DOIUrl":"10.1016/j.jneuroim.2025.578760","url":null,"abstract":"<div><div>MOG antibody-associated disease (MOGAD) diagnosis rests on seropositivity for MOG antibody (MOG-IgG). Live cell-based assays (CBA) are gold standards. Although flow cytometry live CBAs have high real-world sensitivity, their global implementation and diagnostic deployment have been challenged by perceptions of “in-house” design and custom optimization. Herein, we compared the analytical robustness of flow live MOG-IgG CBA across various cytometers in both research and diagnostic laboratories. Flow live CBAs were performed on three conventional (Fortessa, BDLSRII, Gallios), and two spectral cytometers (Aurora, ID7000). MOG-IgG titers were calculated by median fluorescence intensity (MFI), and intra- and inter assay precisions (CV%) and serostatuses were determined. The MFI detection range on Fortessa, currently used for testing, was significantly lower than spectral ID7000 (4.75-fold, <em>p</em> = 0.04) and Aurora (12-fold, <em>p</em> = 0.0001), albeit all MFIs correlated (<em>p</em> < 0.0001; R<sup>2</sup> = 0.99). Interestingly, the high detection range was attributed to technology, not laboratory environments (<em>p</em> > 0.05). Intra- and inter-assay precisions were similar across cytometers. ID7000 and Fortessa had the lowest variation, with 4.6 % and 6.8 % intra-CV, respectively, and 15.7 % inter-CV. FACS ratio, currently reported as MOG-IgG titre, and MFIs were comparable and correlated for all cytometers (<em>p</em> < 0.001; R<sup>2</sup> ≤ 0.99), regardless of the analysis software (<em>p</em> < 0.0001, R<sup>2</sup> = 0.98). All serostatuses were highly concordant (κ = 1). Our results demonstrate that flow live CBAs can be validated in diagnostic laboratories across a range of flow cytometers with high reproducibility and repeatability. In particular, excellent assay performance on spectral flow cytometry strongly supports the proof-of-concept use of this technology for diagnostic purposes.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578760"},"PeriodicalIF":2.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109170","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}
Pub Date : 2025-09-16DOI: 10.1016/j.jneuroim.2025.578759
Xuecong Zhou , Yingsi Li , Yawen Zhao , Xiaoming Yan , Wei Zhang , Yuan Wu
Purpose
This study aims to assess the corneal nerve damage and corneal immune alteration by in vivo confocal microscopy (IVCM) in Fabry disease (FD)
Methods
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
Results
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 (P < 0.001). The density of LCs was significantly increased in the FD group compared with the healthy controls in the central cornea (P = 0.016) and peripheral cornea (P < 0.001). The more severe corneal neuropathy and higher density of LCs were found in hemizygous males than heterozygous females (P < 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
Conclusions
IVCM provides parameters that reliably indicate corneal nerve damage and inflammatory activation in patients with FD
{"title":"Corneal neuro-immune crosstalk in Fabry disease: An in vivo confocal microscopic study","authors":"Xuecong Zhou , Yingsi Li , Yawen Zhao , Xiaoming Yan , Wei Zhang , 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> < 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> < 0.001). The more severe corneal neuropathy and higher density of LCs were found in hemizygous males than heterozygous females (<em>P</em> < 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":"2025-09-16","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}
Pub Date : 2025-09-13DOI: 10.1016/j.jneuroim.2025.578757
Fu-qi Zhu , Wen-jun Zhang , Bao-zhu Guan
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.
{"title":"The role of autophagy in chronic pain","authors":"Fu-qi Zhu , Wen-jun Zhang , 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":"2025-09-13","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}
Pub Date : 2025-09-11DOI: 10.1016/j.jneuroim.2025.578756
Ümit Atasever , Canan Akünal , Hayriye Soytürk
Background
Immune-mediated polyneuropathies such as acute and chronic inflammatory demyelinating polyneuropathy are challenging to diagnose and treat effectively.
Objective
To investigate the diagnostic value of certain biomarkers associated with neuronal inflammation in patients with inflammatory demyelinating polyneuropathy.
Methods
Medical records of patients who presented to the Neurology Clinic of BAİBÜ Education and Research Hospital between December 2023 and October 2024 and underwent lumbar puncture (LP) for diagnostic purposes were retrospectively reviewed. CSF samples and clinical data of 20 AIDP patients, 18 CIDP patients, and 15 patients with pseudotumor cerebri (PTC), included as the unhealthy control group, were analyzed.
Results
The CSF levels of NfL, NfH, GFAP, SM, and BDNF in the AIDP group were significantly higher than those in the PTC group (p < 0.05). In the CIDP group, CSF NfL, GFAP, and SM levels were significantly elevated compared to the PTC group (p < 0.05), while no significant difference was observed in CSF NfH and BDNF levels between the CIDP and PTC groups. Furthermore, the AIDP group had significantly higher levels of NfH and BDNF in CSF compared to the CIDP group (p < 0.05).
Conclusions
These findings suggest that in AIDP and CIDP patients, the elevation of CSF NfL, NfH, and GFAP levels may be associated with secondary proximal axonal damage. Additionally, SM could serve as an indicator of myelin breakdown and remodeling, while the compensatory effect of BDNF may support remyelination. In conclusion, these five biomarkers may represent promising targets for the early diagnosis and differential diagnosis of AIDP and CIDP.
{"title":"Neuronal inflammation-associated biomarkers in cerebrospinal fluid of patients with acute and chronic inflammatory demyelinating polyneuropathies","authors":"Ümit Atasever , Canan Akünal , Hayriye Soytürk","doi":"10.1016/j.jneuroim.2025.578756","DOIUrl":"10.1016/j.jneuroim.2025.578756","url":null,"abstract":"<div><h3>Background</h3><div>Immune-mediated polyneuropathies such as acute and chronic inflammatory demyelinating polyneuropathy are challenging to diagnose and treat effectively.</div></div><div><h3>Objective</h3><div>To investigate the diagnostic value of certain biomarkers associated with neuronal inflammation in patients with inflammatory demyelinating polyneuropathy.</div></div><div><h3>Methods</h3><div>Medical records of patients who presented to the Neurology Clinic of BAİBÜ Education and Research Hospital between December 2023 and October 2024 and underwent lumbar puncture (LP) for diagnostic purposes were retrospectively reviewed. CSF samples and clinical data of 20 AIDP patients, 18 CIDP patients, and 15 patients with pseudotumor cerebri (PTC), included as the unhealthy control group, were analyzed.</div></div><div><h3>Results</h3><div>The CSF levels of NfL, NfH, GFAP, SM, and BDNF in the AIDP group were significantly higher than those in the PTC group (<em>p</em> < 0.05). In the CIDP group, CSF NfL, GFAP, and SM levels were significantly elevated compared to the PTC group (p < 0.05), while no significant difference was observed in CSF NfH and BDNF levels between the CIDP and PTC groups. Furthermore, the AIDP group had significantly higher levels of NfH and BDNF in CSF compared to the CIDP group (p < 0.05).</div></div><div><h3>Conclusions</h3><div>These findings suggest that in AIDP and CIDP patients, the elevation of CSF NfL, NfH, and GFAP levels may be associated with secondary proximal axonal damage. Additionally, SM could serve as an indicator of myelin breakdown and remodeling, while the compensatory effect of BDNF may support remyelination. In conclusion, these five biomarkers may represent promising targets for the early diagnosis and differential diagnosis of AIDP and CIDP.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578756"},"PeriodicalIF":2.5,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145057158","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}
Pub Date : 2025-09-10DOI: 10.1016/j.jneuroim.2025.578755
A.R. Satvik Iyengar , Peter R. Dunkley, Phillip W. Dickson
Parkinson's disease (PD) is the second most common neurodegenerative disorder. It is characterised by loss of dopaminergic neurons in the mid-brain and accumulation of α-synuclein aggregates referred to as Lewy bodies. PD is a progressive disease and the treatments available are aimed at addressing only its symptomatology. Immune dysregulation is one of the several mechanisms that are hypothesized to contribute towards PD pathogenesis. This review firstly addresses the interaction of innate and adaptive immune components and the role of adaptive immune responses, with a particular focus on T lymphocytes in PD. The review secondly examines the evidence for the involvement of the autoimmune system in PD, including the presence of autoantibodies and the association of autoimmunity with proteins linked with PD (α-synuclein and neuromelanin) and with infections. The review thirdly explores the connection between the gut microbiota the immune system and the impact of this relationship on the pathogenic processes of PD. Finally, this review discusses adaptive immunity based therapeutic strategies for PD, probable PD detection approaches based on autoimmunity, and the potential of gut-microbiome replenishment in PD treatment.
{"title":"Immunity in Parkinson's disease - the role of adaptive and auto-immune responses and gut-microbiome axis","authors":"A.R. Satvik Iyengar , Peter R. Dunkley, Phillip W. Dickson","doi":"10.1016/j.jneuroim.2025.578755","DOIUrl":"10.1016/j.jneuroim.2025.578755","url":null,"abstract":"<div><div>Parkinson's disease (PD) is the second most common neurodegenerative disorder. It is characterised by loss of dopaminergic neurons in the mid-brain and accumulation of α-synuclein aggregates referred to as Lewy bodies. PD is a progressive disease and the treatments available are aimed at addressing only its symptomatology. Immune dysregulation is one of the several mechanisms that are hypothesized to contribute towards PD pathogenesis. This review firstly addresses the interaction of innate and adaptive immune components and the role of adaptive immune responses, with a particular focus on T lymphocytes in PD. The review secondly examines the evidence for the involvement of the autoimmune system in PD, including the presence of autoantibodies and the association of autoimmunity with proteins linked with PD (α-synuclein and neuromelanin) and with infections. The review thirdly explores the connection between the gut microbiota the immune system and the impact of this relationship on the pathogenic processes of PD. Finally, this review discusses adaptive immunity based therapeutic strategies for PD, probable PD detection approaches based on autoimmunity, and the potential of gut-microbiome replenishment in PD treatment.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578755"},"PeriodicalIF":2.5,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145047032","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}
Pub Date : 2025-09-09DOI: 10.1016/j.jneuroim.2025.578754
Lohith Karigowda , David Brown , Chong Wong , Kush Deshpande
Anti -N-methyl-d-aspartate receptor antibody (Anti-NMDAR) encephalitis is a serious autoimmune disease that can occur in patients on anti–TNF-α therapy. Adalimumab is a fully human, recombinant monoclonal antibody that inactivates tumour necrosis factor-alpha (TNFα) and is used to treat various autoimmune diseases. The use of Adalimumab has been reported to be associated with autoimmune demyelinating conditions and increases the risk of malignancies. Anti-NMDAR encephalitis associated with anti–TNF-α therapy responds to high-dose corticosteroids, plasma exchange procedures (PLEX), and subsequently, B-cell depletion by the anti-CD20 monoclonal antibody rituximab. A small subset of patients, however, remains refractory to steroids, plasma exchange and rituximab therapy. In these patients, Bortezomib, a proteasome inhibitor, is a potentially effective treatment for those who fail second-line immune therapies.
Here, we report a case of severe anti-NMDAR encephalitis in a 39-year-old man with psoriatic arthritis who was on Adalimumab treatment for two years before symptom onset. He was refractory to high-dose steroids, plasma exchange, intravenous immunoglobulin (IVIg), and rituximab. Four cycles of Bortezomib were administered 44 days after hospital presentation due to non-resolution of symptoms; following which, we observed gradual neurological recovery, and he was discharged after 94 days of hospital admission. This case demonstrates that Bortezomib may be useful in treating refractory cases of anti-NMDAR encephalitis in patients on Adalimumab.
抗- n -甲基-d-天冬氨酸受体抗体（Anti- nmdar）脑炎是一种严重的自身免疫性疾病，可发生在抗tnf -α治疗的患者中。阿达木单抗是一种完全人源的重组单克隆抗体，可灭活肿瘤坏死因子α (TNFα)，用于治疗各种自身免疫性疾病。据报道，阿达木单抗的使用与自身免疫性脱髓鞘疾病相关，并增加恶性肿瘤的风险。与抗tnf -α治疗相关的抗nmdar脑炎对高剂量皮质类固醇、血浆交换程序（PLEX）以及随后的抗cd20单克隆抗体利妥昔单抗b细胞消耗有反应。然而，一小部分患者对类固醇、血浆置换和利妥昔单抗治疗仍然难治。在这些患者中，硼替佐米，一种蛋白酶体抑制剂，对于那些二线免疫治疗失败的患者是一种潜在的有效治疗方法。在这里，我们报告了一例严重的抗nmdar脑炎，患者为一名患有银屑病关节炎的39岁男性，在症状出现前接受阿达木单抗治疗两年。他对大剂量类固醇、血浆置换、静脉注射免疫球蛋白（IVIg）和利妥昔单抗（rituximab）无效。由于症状未缓解，在入院后44天给予4个周期的硼替佐米；随后，我们观察到神经系统逐渐恢复，住院94天后出院。本病例表明，硼替佐米可能有助于治疗阿达木单抗患者抗nmdar脑炎的难治性病例。
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Pub Date : 2025-09-08DOI: 10.1016/j.jneuroim.2025.578751
Marie Mathilde Hansen , Sahla El Mahdaoui , Malene Bredahl Hansen , Victoria Hyslop Hvalkof , Mie Reith Mahler , Signe Refstrup Husted , Helle Bach Søndergaard , Poul Jennum , Jeppe Romme Christensen , Marina Rode von Essen , Finn Sellebjerg
Background
Mononuclear phagocytes, including monocytes, macrophages, and microglia, play key roles in the immunopathogenesis of multiple sclerosis (MS). While anti-CD20 monoclonal antibody therapies effectively treat relapsing-remitting MS (RRMS), their secondary effects on mononuclear phagocytes remain unclear.
Objective and methods
We analyzed blood and cerebrospinal fluid (CSF) mononuclear phagocytes in patients with RRMS treated with anti-CD20 therapy for 6 months, untreated patients, and controls. Flow cytometry was used to assess the prevalence, phenotype, and cytokine production by blood monocytes. Chitinase-1 (CHIT1) levels in CSF were measured using an enzyme-linked immunosorbent assay.
Results
Blood monocyte frequencies were elevated in untreated and anti-CD20-treated RRMS patients compared with controls. CSF mononuclear phagocytes differed from blood monocytes and were classified as either CD16+ or CD16−, with CD16+ mononuclear phagocytes being enriched in all groups. However, the frequencies of CD16− mononuclear phagocytes in CSF were higher in untreated and anti-CD20-treated RRMS patients compared to controls, and the expression of CD206 and CCR2 on CD16− mononuclear phagocytes differed between untreated patients and controls. Blood monocyte cytokine production did not differ between untreated and anti-CD20-treated patients. CSF CHIT1 levels were elevated in both untreated and anti-CD20-treated patients.
Conclusions
The comparable blood and CSF mononuclear phagocyte phenotypes, along with persistently elevated CHIT1 concentrations in CSF of untreated and anti-CD20-treated patients with RRMS, suggest that residual innate immune activation is not normalized by 6 months of anti-CD20 treatment.
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