Transitioning from sphingosine-1-phosphate modulators, such as fingolimod, to anti-CD20 therapies is common in patients with multiple sclerosis due to suboptimal disease control, progression, or family planning. However, the optimal washout period remains unclear, and cases of disease activity rebound following discontinuation of fingolimod have been documented. We present the case of a 43-year-old woman who developed severe rebound disease activity after transitioning from fingolimod to ofatumumab, despite a washout period of 28 days. The patient experienced a new lesion and neuropsychological impairment, which improved after treatment with high-dose methylprednisolone. Literature review highlights the complexity of factors influencing rebound, including washout duration, lymphocyte count, and disease control during fingolimod therapy. Evidence suggests that initiating ofatumumab treatment without a prolonged washout period may mitigate rebound risk.
{"title":"Wash-out duration and lymphocyte count in switching from fingolimod to ofatumumab: A case report and literature review","authors":"Assunta Bianco , Rosellina Russo , Alessandra Cicia , Sofia Marini , Matteo Lucchini , Massimiliano Mirabella","doi":"10.1016/j.jneuroim.2025.578808","DOIUrl":"10.1016/j.jneuroim.2025.578808","url":null,"abstract":"<div><div>Transitioning from sphingosine-1-phosphate modulators, such as fingolimod, to anti-CD20 therapies is common in patients with multiple sclerosis due to suboptimal disease control, progression, or family planning. However, the optimal washout period remains unclear, and cases of disease activity rebound following discontinuation of fingolimod have been documented. We present the case of a 43-year-old woman who developed severe rebound disease activity after transitioning from fingolimod to ofatumumab, despite a washout period of 28 days. The patient experienced a new lesion and neuropsychological impairment, which improved after treatment with high-dose methylprednisolone. Literature review highlights the complexity of factors influencing rebound, including washout duration, lymphocyte count, and disease control during fingolimod therapy. Evidence suggests that initiating ofatumumab treatment without a prolonged washout period may mitigate rebound risk.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"410 ","pages":"Article 578808"},"PeriodicalIF":2.5,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145615382","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 : 2025-11-14DOI: 10.1016/j.jneuroim.2025.578796
Ruojie He , Zhanhua Zhong , Huiyu Feng, Xiaoli Yao
Objective
To assess the treatment effecitiveness and safety of Chinese patients with chronic inflammatory demyelinating polyneuropathy (CIDP) treated with intravenous efgartigimod in this real-world study.
Methods
This study analyzed data retrospectively from 13 patients with CIDP treated with efgartigimod at the Department of Neurology, First Affiliated Hospital of Sun Yat-Sen University from December 2023 to September 2024. Clinical assessment scales included the Inflammatory Neuropathy Cause and Treatment (INCAT) score and the Medical Research Council (MRC) sum score were utilized to evalutate effecitiveness before and after efgartigimod treatments. Adverse events werer monitored to assess the safety of efgartigimod treatments.
Results
The mean onset age of 13 patients was 38.3 years, and the mean duration from symptom onset to diagnosis was 13.1 months. About 46 % patients in our study were typical CIDP subtype. About 77 % patients experienced relapses before efgartigimod treatments. Clinical improvements were observed in 12 patients (92.3 %) with at least 1-point decrease on INCAT scores at 12 weeks follow-up, indicating efgartigimod treatment effectiveness. Eleven patients (84.6 %) achieved clinical improvements at 24 weeks follow-up. At last follow-up, five patients (38.5 %) had discontinued immunotherapy. Adverse events monitoring revealed that only one patient had pruritus which alleviated spontaneously.
Conclusion
This case series real-world study support the efficacy and safety of efgartigimod treatment in CIDP patients, benefit on partially reducing the usage of glucocorticoids and immunosuppressants. It was well tolerated across age groups. Larger prospective studies are needed to refine dosing and establish guidelines for CIDP management.
{"title":"Efficacy and safety of intravenous efgartigimod for chronic inflammatory demyelinating polyneuropathy: A case series real-world study","authors":"Ruojie He , Zhanhua Zhong , Huiyu Feng, Xiaoli Yao","doi":"10.1016/j.jneuroim.2025.578796","DOIUrl":"10.1016/j.jneuroim.2025.578796","url":null,"abstract":"<div><h3>Objective</h3><div>To assess the treatment effecitiveness and safety of Chinese patients with chronic inflammatory demyelinating polyneuropathy (CIDP) treated with intravenous efgartigimod in this real-world study.</div></div><div><h3>Methods</h3><div>This study analyzed data retrospectively from 13 patients with CIDP treated with efgartigimod at the Department of Neurology, First Affiliated Hospital of Sun Yat-Sen University from December 2023 to September 2024. Clinical assessment scales included the Inflammatory Neuropathy Cause and Treatment (INCAT) score and the Medical Research Council (MRC) sum score were utilized to evalutate effecitiveness before and after efgartigimod treatments. Adverse events werer monitored to assess the safety of efgartigimod treatments.</div></div><div><h3>Results</h3><div>The mean onset age of 13 patients was 38.3 years, and the mean duration from symptom onset to diagnosis was 13.1 months. About 46 % patients in our study were typical CIDP subtype. About 77 % patients experienced relapses before efgartigimod treatments. Clinical improvements were observed in 12 patients (92.3 %) with at least 1-point decrease on INCAT scores at 12 weeks follow-up, indicating efgartigimod treatment effectiveness. Eleven patients (84.6 %) achieved clinical improvements at 24 weeks follow-up. At last follow-up, five patients (38.5 %) had discontinued immunotherapy. Adverse events monitoring revealed that only one patient had pruritus which alleviated spontaneously.</div></div><div><h3>Conclusion</h3><div>This case series real-world study support the efficacy and safety of efgartigimod treatment in CIDP patients, benefit on partially reducing the usage of glucocorticoids and immunosuppressants. It was well tolerated across age groups. Larger prospective studies are needed to refine dosing and establish guidelines for CIDP management.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"410 ","pages":"Article 578796"},"PeriodicalIF":2.5,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145564293","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 : 2025-11-10DOI: 10.1016/j.jneuroim.2025.578806
Young Nam Kwon , Woohee Ju , Jae hyun Jeon , Chorong Hahm , Jung-Joon Sung , Sung-Min Kim
Background
MOG-Ab assay is a sensitive and specific biomarker that is indispensable in diagnosis of MOG antibody-associated disease (MOGAD). However, its accuracy can largely depend on a proper selection of patients also on cut-off value setting. We updated the cut-off value of flow cytometric MOG antibody assay in Korea, into low- and clear-positive, in alignment with 2023 International MOGAD Panel proposal.
Methods
We retrospectively analyzed 695 patients who underwent live cell-based flow cytometric MOG-Ab testing at Seoul National University Hospital from August 2023 to January 2024. Cut-off values for mean fluorescence intensity ratio (MFIr) were determined using disease controls, and diagnostic accuracy was assessed at three thresholds: Low Positive (>2.61), Clear-Positive (>5.66), and High Clear-Positive (>10.0).
Results
Among 671 non-MS/NMOSD patients, 159 had core clinical demyelinating events, and 66 met 2023 international panel criteria for MOGAD. The diagnostic accuracies for low-positive, clear-positive, and high clear-positive results were as follows: sensitivity of 100 %, 59.1 %, and 33.3 %, respectively; specificity of 95.7 %, 95.9 %, and 100 %; positive predictive value (PPV) of 71.0 %, 90.7 %, and 100 %; and negative predictive value of 100 %, 95.9 %, and 93.5 %. In 159 patients with core clinical demyelinating events excluding MS and NMOSD, clear-positive threshold demonstrated a PPV of 100 %.
Conclusion
This study updates the cut-off values of flow cytometric MOG-Ab assay and its diagnostic accuracies in Korea in accordance with the 2023 International Panel recommendation. Our findings can contribute to improving the diagnostic accuracy of MOGAD in Korea and to strengthening the scientific validity of MOGAD research data from Korean cohort.
{"title":"Clear-positive cut off determination of flow cytometric MOG-antibody assay in Korea: Alignment with international MOGAD diagnostic standards","authors":"Young Nam Kwon , Woohee Ju , Jae hyun Jeon , Chorong Hahm , Jung-Joon Sung , Sung-Min Kim","doi":"10.1016/j.jneuroim.2025.578806","DOIUrl":"10.1016/j.jneuroim.2025.578806","url":null,"abstract":"<div><h3>Background</h3><div>MOG-Ab assay is a sensitive and specific biomarker that is indispensable in diagnosis of MOG antibody-associated disease (MOGAD). However, its accuracy can largely depend on a proper selection of patients also on cut-off value setting. We updated the cut-off value of flow cytometric MOG antibody assay in Korea, into low- and clear-positive, in alignment with 2023 International MOGAD Panel proposal.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed 695 patients who underwent live cell-based flow cytometric MOG-Ab testing at Seoul National University Hospital from August 2023 to January 2024. Cut-off values for mean fluorescence intensity ratio (MFIr) were determined using disease controls, and diagnostic accuracy was assessed at three thresholds: Low Positive (>2.61), Clear-Positive (>5.66), and High Clear-Positive (>10.0).</div></div><div><h3>Results</h3><div>Among 671 non-MS/NMOSD patients, 159 had core clinical demyelinating events, and 66 met 2023 international panel criteria for MOGAD. The diagnostic accuracies for low-positive, clear-positive, and high clear-positive results were as follows: sensitivity of 100 %, 59.1 %, and 33.3 %, respectively; specificity of 95.7 %, 95.9 %, and 100 %; positive predictive value (PPV) of 71.0 %, 90.7 %, and 100 %; and negative predictive value of 100 %, 95.9 %, and 93.5 %. In 159 patients with core clinical demyelinating events excluding MS and NMOSD, clear-positive threshold demonstrated a PPV of 100 %.</div></div><div><h3>Conclusion</h3><div>This study updates the cut-off values of flow cytometric MOG-Ab assay and its diagnostic accuracies in Korea in accordance with the 2023 International Panel recommendation. Our findings can contribute to improving the diagnostic accuracy of MOGAD in Korea and to strengthening the scientific validity of MOGAD research data from Korean cohort.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"410 ","pages":"Article 578806"},"PeriodicalIF":2.5,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145564367","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 : 2025-11-10DOI: 10.1016/j.jneuroim.2025.578805
Chiara Marotta , Elisabetta Rolla , Martina Fabris , Rossana Domenis , Jérôme Honnorat , Donatella Iacono , Giuseppe Aprile , Mariarosaria Valente , Alberto Vogrig
Immune checkpoint inhibitors (ICIs) have radically improved cancer therapy but are associated with a spectrum of immune-related adverse events (irAEs), including infrequent (1–3 %) neurological complications. Pembrolizumab, an anti-PD-1 monoclonal antibody, enhances antitumor immunity but may disrupt self-tolerance, leading to autoimmune phenomena. This case report describes a patient with triple metachronous malignancies (cerebral hemangioblastoma, clear cell renal carcinoma, and non-small cell lung cancer, NSCLC), who developed glial fibrillary acidic protein (GFAP)-antibody-associated autoimmune encephalitis following pembrolizumab therapy initiated as NSCLC treatment. The clinical course was marked by subacute neurocognitive decline followed by new-onset refractory status epilepticus (NORSE). Diagnostic workup revealed GFAP antibodies in cerebrospinal fluid as well as serum, with no evidence of tumor progression or infectious causes. Although GFAP astrocytopathy has been rarely linked to ICIs, this appears to be the first report manifesting with NORSE. The temporal association with cancer immunotherapy, the presence of GFAP autoantibodies, and a positive steroid response collectively suggest that ICI-induced immune dysregulation is the primary disease mechanism. This report, in conjunction with other isolated descriptions form the literature with other antibody specificities, paves the way to a new spectrum of etiologies for NORSE, namely iatrogenic causes related to cancer immunotherapy.
{"title":"Iatrogenic NORSE: Immune checkpoint inhibitor-related anti-GFAP autoimmune astrocytopathy","authors":"Chiara Marotta , Elisabetta Rolla , Martina Fabris , Rossana Domenis , Jérôme Honnorat , Donatella Iacono , Giuseppe Aprile , Mariarosaria Valente , Alberto Vogrig","doi":"10.1016/j.jneuroim.2025.578805","DOIUrl":"10.1016/j.jneuroim.2025.578805","url":null,"abstract":"<div><div>Immune checkpoint inhibitors (ICIs) have radically improved cancer therapy but are associated with a spectrum of immune-related adverse events (irAEs), including infrequent (1–3 %) neurological complications. Pembrolizumab, an anti-PD-1 monoclonal antibody, enhances antitumor immunity but may disrupt self-tolerance, leading to autoimmune phenomena. This case report describes a patient with triple metachronous malignancies (cerebral hemangioblastoma, clear cell renal carcinoma, and non-small cell lung cancer, NSCLC), who developed glial fibrillary acidic protein (GFAP)-antibody-associated autoimmune encephalitis following pembrolizumab therapy initiated as NSCLC treatment. The clinical course was marked by subacute neurocognitive decline followed by new-onset refractory status epilepticus (NORSE). Diagnostic workup revealed GFAP antibodies in cerebrospinal fluid as well as serum, with no evidence of tumor progression or infectious causes. Although GFAP astrocytopathy has been rarely linked to ICIs, this appears to be the first report manifesting with NORSE. The temporal association with cancer immunotherapy, the presence of GFAP autoantibodies, and a positive steroid response collectively suggest that ICI-induced immune dysregulation is the primary disease mechanism. This report, in conjunction with other isolated descriptions form the literature with other antibody specificities, paves the way to a new spectrum of etiologies for NORSE, namely iatrogenic causes related to cancer immunotherapy.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"410 ","pages":"Article 578805"},"PeriodicalIF":2.5,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145513088","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}
Autoimmune encephalitis (AE) is increasingly recognized in clinical practice, yet drug-related encephalitic syndromes remain a diagnostic challenge. Immune checkpoint inhibitors (ICIs) are well-established triggers, whereas vascular endothelial growth factor (VEGF) inhibitors such as Bevacizumab are only rarely implicated, with evidence confined to case reports. Awareness of this association is essential as targeted therapies gain prominence in metastatic cancer care.
Case presentation
We describe a 58-year-old woman with hypothyroidism and advanced ovarian carcinoma, who had previously undergone surgery and adjuvant chemotherapy in 2022 and metastasectomy for bowel involvement in 2024. She was in remission under Bevacizumab–chemotherapy combination therapy when, following reoperation for peritoneal adhesions in February 2025, she developed two episodes of transient loss of consciousness. During the attacks, fluctuating blood pressure, visual phenomena, and transient foreign-language speech were observed. MRI initially revealed left occipital leptomeningeal enhancement, and EEG showed lateralized epileptiform discharges and non-convulsive status epilepticus was considered. Although initial events were interpreted as seizure-related changes, follow-up imaging on day 15 revealed persistent abnormalities with new cortical and thalamic FLAIR hyperintensities. Neurological examination demonstrated drowsy consciousness, right homonymous hemianopia, motor aphasia, dystonic posturing of the right hand, and sensory integration deficits. Cerebrospinal fluid cytology, paraneoplastic, and autoimmune antibody panels were negative. Pulse intravenous methylprednisolone was initiated, leading to significant clinical improvement and partial radiologic regression, although word-finding difficulties persisted at last follow-up.
Conclusion
This case illustrates an atypical, steroid-responsive encephalitic syndrome temporally associated with Bevacizumab. Unlike the well-characterized bilateral parieto-occipital patterns of PRES, our patient demonstrated unilateral leptomeningeal and cortical–thalamic involvement. The case underscores the importance of repeated neuroimaging, systematic exclusion of alternative etiologies, and timely immunotherapy in suspected drug-related encephalitis. Accumulation of further cases will be essential to clarify incidence, mechanisms, and optimal management of Bevacizumab-associated encephalitis.
{"title":"Autoimmune encephalitis following bevacizumab therapy in ovarian carcinoma: A case report and review","authors":"Bengül Fatma Gölge , Cansu Sarıkaya , Canan Aykut Bingöl , Berrin Aktekin , Rana Karabudak , Gazanfer Ekinci , Serkan Çelik","doi":"10.1016/j.jneuroim.2025.578804","DOIUrl":"10.1016/j.jneuroim.2025.578804","url":null,"abstract":"<div><h3>Background</h3><div>Autoimmune encephalitis (AE) is increasingly recognized in clinical practice, yet drug-related encephalitic syndromes remain a diagnostic challenge. Immune checkpoint inhibitors (ICIs) are well-established triggers, whereas vascular endothelial growth factor (VEGF) inhibitors such as Bevacizumab are only rarely implicated, with evidence confined to case reports. Awareness of this association is essential as targeted therapies gain prominence in metastatic cancer care.</div></div><div><h3>Case presentation</h3><div>We describe a 58-year-old woman with hypothyroidism and advanced ovarian carcinoma, who had previously undergone surgery and adjuvant chemotherapy in 2022 and metastasectomy for bowel involvement in 2024. She was in remission under Bevacizumab–chemotherapy combination therapy when, following reoperation for peritoneal adhesions in February 2025, she developed two episodes of transient loss of consciousness. During the attacks, fluctuating blood pressure, visual phenomena, and transient foreign-language speech were observed. MRI initially revealed left occipital leptomeningeal enhancement, and EEG showed lateralized epileptiform discharges and non-convulsive status epilepticus was considered. Although initial events were interpreted as seizure-related changes, follow-up imaging on day 15 revealed persistent abnormalities with new cortical and thalamic FLAIR hyperintensities. Neurological examination demonstrated drowsy consciousness, right homonymous hemianopia, motor aphasia, dystonic posturing of the right hand, and sensory integration deficits. Cerebrospinal fluid cytology, paraneoplastic, and autoimmune antibody panels were negative. Pulse intravenous methylprednisolone was initiated, leading to significant clinical improvement and partial radiologic regression, although word-finding difficulties persisted at last follow-up.</div></div><div><h3>Conclusion</h3><div>This case illustrates an atypical, steroid-responsive encephalitic syndrome temporally associated with Bevacizumab. Unlike the well-characterized bilateral parieto-occipital patterns of PRES, our patient demonstrated unilateral leptomeningeal and cortical–thalamic involvement. The case underscores the importance of repeated neuroimaging, systematic exclusion of alternative etiologies, and timely immunotherapy in suspected drug-related encephalitis. Accumulation of further cases will be essential to clarify incidence, mechanisms, and optimal management of Bevacizumab-associated encephalitis.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"410 ","pages":"Article 578804"},"PeriodicalIF":2.5,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145517667","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 : 2025-11-08DOI: 10.1016/j.jneuroim.2025.578802
Nirmalya Ray , Russoti Das , Mithun Sekhar , Debraj Jash , Shramana Deb , Ritwick Mondal , Jayanta Roy , Julián Benito-León
Background
Neurosarcoidosis is a rare inflammatory condition that can occasionally present with recurrent tumefactive lesions resembling those of idiopathic demyelinating diseases. Diagnosis is frequently delayed because clinical and radiological features overlap with demyelinating disorders, and systemic signs may initially be absent.
Case presentation
We report a woman who first presented at 23 years of age with a tumefactive demyelinating-appearing brain lesion and, eight years later, experienced recurrence with new involvement of the brain and spinal cord. The second episode featured a new tumefactive demyelinating-appearing brain lesion, longitudinally extensive transverse myelitis, vertebral enhancement, and systemic manifestations. Imaging revealed mediastinal lymphadenopathy and multiple hypodense lesions in the liver and spleen, while histopathologic examination of a mediastinal lymph node demonstrated noncaseating granulomas, confirming sarcoidosis.
Conclusion
To our knowledge, this is the first detailed report of neurosarcoidosis evolving from an initially isolated tumefactive demyelinating-appearing brain lesion to a later episode characterized by recurrent brain involvement with simultaneous spinal and systemic disease after a prolonged asymptomatic interval. Clinicians should consider neurosarcoidosis in the differential diagnosis of tumefactive demyelinating-appearing brain lesions, particularly when an initially isolated presentation is followed by subsequent brain, spinal, and systemic involvement, even in young patients without systemic features at onset.
{"title":"Neurosarcoidosis masquerading as recurrent tumefactive demyelinating-appearing brain lesions: An 8-year diagnostic odyssey","authors":"Nirmalya Ray , Russoti Das , Mithun Sekhar , Debraj Jash , Shramana Deb , Ritwick Mondal , Jayanta Roy , Julián Benito-León","doi":"10.1016/j.jneuroim.2025.578802","DOIUrl":"10.1016/j.jneuroim.2025.578802","url":null,"abstract":"<div><h3>Background</h3><div>Neurosarcoidosis is a rare inflammatory condition that can occasionally present with recurrent tumefactive lesions resembling those of idiopathic demyelinating diseases. Diagnosis is frequently delayed because clinical and radiological features overlap with demyelinating disorders, and systemic signs may initially be absent.</div></div><div><h3>Case presentation</h3><div>We report a woman who first presented at 23 years of age with a tumefactive demyelinating-appearing brain lesion and, eight years later, experienced recurrence with new involvement of the brain and spinal cord. The second episode featured a new tumefactive demyelinating-appearing brain lesion, longitudinally extensive transverse myelitis, vertebral enhancement, and systemic manifestations. Imaging revealed mediastinal lymphadenopathy and multiple hypodense lesions in the liver and spleen, while histopathologic examination of a mediastinal lymph node demonstrated noncaseating granulomas, confirming sarcoidosis.</div></div><div><h3>Conclusion</h3><div>To our knowledge, this is the first detailed report of neurosarcoidosis evolving from an initially isolated tumefactive demyelinating-appearing brain lesion to a later episode characterized by recurrent brain involvement with simultaneous spinal and systemic disease after a prolonged asymptomatic interval. Clinicians should consider neurosarcoidosis in the differential diagnosis of tumefactive demyelinating-appearing brain lesions, particularly when an initially isolated presentation is followed by subsequent brain, spinal, and systemic involvement, even in young patients without systemic features at onset.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"410 ","pages":"Article 578802"},"PeriodicalIF":2.5,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145495885","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}
Baló's concentric sclerosis (BCS) is a rare demyelinating disorder with concentric ring lesions on MRI, which can mimic tumefactive demyelinating lesions (TDL), especially present in tumefactive multiple sclerosis (TMS). Recent neuropathological studies suggest the involvement of activated microglia and astrocytes in BCS lesion expansion. However, advanced imaging techniques like Quantitative Susceptibility Mapping (QSM) and Magnetic Resonance Spectroscopy (MRS) have not been fully utilized to differentiate BCS from other TDL or explore their metabolic differences.
Methods
We retrospectively analyzed MRI data from 12 BCS patients (mean age 29.6 years, 50 % male) and 16 patients with TDL (mean age 30.9 years, 37.5 % male). MRS and QSM data were stratified into acute/subacute and chronic phases. Long echo-time acquisitions (TE =144 ms) were used for metabolite ratio analysis, while short echo-time (TE =35 ms) allowed absolute quantification of 34 metabolites. Lesion, peri-lesional, and normal-appearing white matter (NAWM) regions were compared. Patients tested positive for MOG or AQP4 were excluded.
Results
In long echo-time MRS, BCS lesions demonstrated lower Cho/Cr (p = 0.0029) and Cho/NAA (p = 0.019) ratios compared to TDL, indicating greater axonal preservation and lower cellular turnover in BCS. When compared to their respective NAWM, BCS lesions exhibited significantly reduced NAA/Cr (p = 0.001) and TDL reduced NAA/Cr (p = 0.002), Cho/Cr (p = 0.001), and increased Cho/NAA (p < 0.0001). Absolute quantification showed increased myo-inositol in BCS lesions, while TDL showed increased glutamate metabolism. Layer-wise QSM analysis revealed a centrifugal gradient in BCS lesions, with the core exhibiting the highest susceptibility.
Conclusion
BCS presents distinct metabolic and structural features compared to TDL, with biomarkers such as lower Cho/Cr ratios, elevated myo-inositol, and centrifugal QSM gradients, which may enhance diagnostic accuracy and provide insight into lesion expansion.
{"title":"Advanced quantitative MRI reveals a unique pattern of metabolic alterations and iron-pathology linked to glial activation in Baló's concentric sclerosis","authors":"Christina-Athanasia Dempegioti , Giorgos Broumpoulis , Maria-Evgenia Brinia , Ioannis Papadopoulos , Efstratios Karavasilis , Maria-Eleftheria Evangelopoulos , Leonidas Stefanis , Christine Stadelmann , Georgios Velonakis , Constantinos Kilidireas , Aigli G. Vakrakou","doi":"10.1016/j.jneuroim.2025.578798","DOIUrl":"10.1016/j.jneuroim.2025.578798","url":null,"abstract":"<div><h3>Background</h3><div>Baló's concentric sclerosis (BCS) is a rare demyelinating disorder with concentric ring lesions on MRI, which can mimic tumefactive demyelinating lesions (TDL), especially present in tumefactive multiple sclerosis (TMS). Recent neuropathological studies suggest the involvement of activated microglia and astrocytes in BCS lesion expansion. However, advanced imaging techniques like Quantitative Susceptibility Mapping (QSM) and Magnetic Resonance Spectroscopy (MRS) have not been fully utilized to differentiate BCS from other TDL or explore their metabolic differences.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed MRI data from 12 BCS patients (mean age 29.6 years, 50 % male) and 16 patients with TDL (mean age 30.9 years, 37.5 % male). MRS and QSM data were stratified into acute/subacute and chronic phases. Long echo-time acquisitions (TE =144 ms) were used for metabolite ratio analysis, while short echo-time (TE =35 ms) allowed absolute quantification of 34 metabolites. Lesion, peri-lesional, and normal-appearing white matter (NAWM) regions were compared. Patients tested positive for MOG or AQP4 were excluded.</div></div><div><h3>Results</h3><div>In long echo-time MRS, BCS lesions demonstrated lower Cho/Cr (<em>p</em> = 0.0029) and Cho/NAA (<em>p</em> = 0.019) ratios compared to TDL, indicating greater axonal preservation and lower cellular turnover in BCS. When compared to their respective NAWM, BCS lesions exhibited significantly reduced NAA/Cr (<em>p</em> = 0.001) and TDL reduced NAA/Cr (<em>p</em> = 0.002), Cho/Cr (p = 0.001), and increased Cho/NAA (<em>p</em> < 0.0001). Absolute quantification showed increased myo-inositol in BCS lesions, while TDL showed increased glutamate metabolism. Layer-wise QSM analysis revealed a centrifugal gradient in BCS lesions, with the core exhibiting the highest susceptibility.</div></div><div><h3>Conclusion</h3><div>BCS presents distinct metabolic and structural features compared to TDL, with biomarkers such as lower Cho/Cr ratios, elevated myo-inositol, and centrifugal QSM gradients, which may enhance diagnostic accuracy and provide insight into lesion expansion.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"410 ","pages":"Article 578798"},"PeriodicalIF":2.5,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145482174","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 : 2025-11-07DOI: 10.1016/j.jneuroim.2025.578800
Minghao Xie , Yuhang Diao , Jing Zhang , Mingyu Hao , Zhitan Wang , Rui Tan , Jing Ma , Xiaojun Hu , Zhenghao Hao , Tao Zhu
Background
Neuroinflammation following spinal cord injury (SCI) is a critical contributor to secondary damage. This inflammatory response disrupts the integrity of the blood-spinal cord barrier (BSCB), leading to neural tissue edema and impaired neural function. Interleukin-33 (IL-33), a tissue-derived cytokine belonging to the IL-1 family, is detectable in both tissues and blood following neural injury. While the neuroprotective effects of exogenous IL-33 have been demonstrated in models of traumatic brain injury (TBI) and epilepsy, its role in spinal cord injury remains unexplored. Therefore, this study employs a mouse spinal cord contusion model to investigate the potential role of exogenous IL-33 in BSCB repair.
Methods
We established a spinal cord contusion model in mice and administered exogenous IL-33 via intraperitoneal injection to investigate its mechanisms in neural repair. Behavioral assessments were conducted on days 1, 3, 7, and 14 post-SCI, revealing the effects of IL-33 on long-term neural function. Additionally, immunofluorescence staining, Western blotting, ELISA, Evans blue leakage assays, TUNEL staining, hematoxylin-eosin (HE) staining, and Nissl staining were performed on day 3 or 7 post-SCI to evaluate the impact of IL-33 on neuroinflammation, BSCB integrity, and neuronal apoptosis.
Results
We found that exogenous IL-33 significantly promoted neural functional recovery in SCI mice, with particularly pronounced effects observed after 7 days. Subsequent analysis confirmed that IL-33 was primarily expressed in the nuclei of astrocytes following SCI and exhibited high expression levels in the spinal cord of SCI mice. Exogenous IL-33 modulated the NF-κB signaling pathway, suppressing the expression of downstream pro-inflammatory cytokines. Additionally, IL-33 inhibited microglial activation and facilitated their polarization toward an anti-inflammatory phenotype, thereby mitigating spinal cord inflammation.Furthermore, the administration of recombinant IL-33 increased the expression of tight junction proteins, including ZO-1, Occludin, and Claudin-5. These changes contributed to BSCB repair, reducing spinal cord edema and improving neurological recovery in mice. Lastly, IL-33 demonstrated a protective effect against neuronal apoptosis, further underscoring its neuroprotective potential.
Concusion
In summary, we demonstrated the anti-inflammatory and anti-apoptotic effects of exogenous IL-33, elucidating its underlying mechanisms. Notably, we identified its role in promoting BSCB repair for the first time. These findings support the potential use of exogenous IL-33 as a therapeutic strategy for early intervention in spinal cord injury.
{"title":"Exogenous IL-33 mitigates inflammatory responses by suppressing the NF-Κb signaling pathway, promoting blood-spinal cord barrier repair and neural functional recovery","authors":"Minghao Xie , Yuhang Diao , Jing Zhang , Mingyu Hao , Zhitan Wang , Rui Tan , Jing Ma , Xiaojun Hu , Zhenghao Hao , Tao Zhu","doi":"10.1016/j.jneuroim.2025.578800","DOIUrl":"10.1016/j.jneuroim.2025.578800","url":null,"abstract":"<div><h3>Background</h3><div>Neuroinflammation following spinal cord injury (SCI) is a critical contributor to secondary damage. This inflammatory response disrupts the integrity of the blood-spinal cord barrier (BSCB), leading to neural tissue edema and impaired neural function. Interleukin-33 (IL-33), a tissue-derived cytokine belonging to the IL-1 family, is detectable in both tissues and blood following neural injury. While the neuroprotective effects of exogenous IL-33 have been demonstrated in models of traumatic brain injury (TBI) and epilepsy, its role in spinal cord injury remains unexplored. Therefore, this study employs a mouse spinal cord contusion model to investigate the potential role of exogenous IL-33 in BSCB repair.</div></div><div><h3>Methods</h3><div>We established a spinal cord contusion model in mice and administered exogenous IL-33 via intraperitoneal injection to investigate its mechanisms in neural repair. Behavioral assessments were conducted on days 1, 3, 7, and 14 post-SCI, revealing the effects of IL-33 on long-term neural function. Additionally, immunofluorescence staining, Western blotting, ELISA, Evans blue leakage assays, TUNEL staining, hematoxylin-eosin (HE) staining, and Nissl staining were performed on day 3 or 7 post-SCI to evaluate the impact of IL-33 on neuroinflammation, BSCB integrity, and neuronal apoptosis.</div></div><div><h3>Results</h3><div>We found that exogenous IL-33 significantly promoted neural functional recovery in SCI mice, with particularly pronounced effects observed after 7 days. Subsequent analysis confirmed that IL-33 was primarily expressed in the nuclei of astrocytes following SCI and exhibited high expression levels in the spinal cord of SCI mice. Exogenous IL-33 modulated the NF-κB signaling pathway, suppressing the expression of downstream pro-inflammatory cytokines. Additionally, IL-33 inhibited microglial activation and facilitated their polarization toward an anti-inflammatory phenotype, thereby mitigating spinal cord inflammation.Furthermore, the administration of recombinant IL-33 increased the expression of tight junction proteins, including ZO-1, Occludin, and Claudin-5. These changes contributed to BSCB repair, reducing spinal cord edema and improving neurological recovery in mice. Lastly, IL-33 demonstrated a protective effect against neuronal apoptosis, further underscoring its neuroprotective potential.</div></div><div><h3>Concusion</h3><div>In summary, we demonstrated the anti-inflammatory and anti-apoptotic effects of exogenous IL-33, elucidating its underlying mechanisms. Notably, we identified its role in promoting BSCB repair for the first time. These findings support the potential use of exogenous IL-33 as a therapeutic strategy for early intervention in spinal cord injury.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"410 ","pages":"Article 578800"},"PeriodicalIF":2.5,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145468396","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 : 2025-11-06DOI: 10.1016/j.jneuroim.2025.578801
Alexandra L. Palmer , Ruiqi Wang , Yohan R. Zonta , Zachary D.J. Bailey , Hedwich F. Kuipers , Shalina S. Ousman
Astrocytes play essential roles during homeostasis as structural and functional components of tripartite synapse signaling, blood brain barrier integrity, and neurotransmitter buffering. However, these glia can become reactive in diseases such as multiple sclerosis (MS), where they can exacerbate pro-inflammatory environments by recruiting and promoting immune cell activity through secretion of cytokines and chemokines and possibly antigen presentation. What is incompletely known are the molecular regulators of astrocyte activation. Variable levels of Cst3 mRNA and Cystatin C (CysC) protein have been recorded in a variety of MS tissues, and CysC plays a detrimental role in the experimental autoimmune encephalomyelitis (EAE) model of MS. Further, CysC promotes glial fibrillary acidic protein (Gfap) expression, and contributes to the number of GFAP-positive cells during development. As such, we investigated if CysC is expressed by astrocytes in MS and EAE central nervous system (CNS) cord tissue, and what the functional consequence may be of CysC expression in these glia. We found that CysC is robustly expressed by astrocytes in MS and EAE CNS tissues, that CysC contributes to cytokine and chemokine production by mixed glial cells enriched in astrocytes, and that these CysC-impacted secretory factors can promote cytokine production by CD4+ T cells in vitro. Thus, CysC expression in astrocytes contributes to activation of these glial cells.
{"title":"Cytokine and chemokine production by astrocytes is influenced by Cystatin C","authors":"Alexandra L. Palmer , Ruiqi Wang , Yohan R. Zonta , Zachary D.J. Bailey , Hedwich F. Kuipers , Shalina S. Ousman","doi":"10.1016/j.jneuroim.2025.578801","DOIUrl":"10.1016/j.jneuroim.2025.578801","url":null,"abstract":"<div><div>Astrocytes play essential roles during homeostasis as structural and functional components of tripartite synapse signaling, blood brain barrier integrity, and neurotransmitter buffering. However, these glia can become reactive in diseases such as multiple sclerosis (MS), where they can exacerbate pro-inflammatory environments by recruiting and promoting immune cell activity through secretion of cytokines and chemokines and possibly antigen presentation. What is incompletely known are the molecular regulators of astrocyte activation. Variable levels of <em>Cst3</em> mRNA and Cystatin C (CysC) protein have been recorded in a variety of MS tissues, and CysC plays a detrimental role in the experimental autoimmune encephalomyelitis (EAE) model of MS. Further, CysC promotes glial fibrillary acidic protein (<em>Gfap</em>) expression, and contributes to the number of GFAP-positive cells during development. As such, we investigated if CysC is expressed by astrocytes in MS and EAE central nervous system (CNS) cord tissue, and what the functional consequence may be of CysC expression in these glia. We found that CysC is robustly expressed by astrocytes in MS and EAE CNS tissues, that CysC contributes to cytokine and chemokine production by mixed glial cells enriched in astrocytes, and that these CysC-impacted secretory factors can promote cytokine production by CD4<sup>+</sup> T cells in vitro. Thus, CysC expression in astrocytes contributes to activation of these glial cells.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"410 ","pages":"Article 578801"},"PeriodicalIF":2.5,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145517670","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 : 2025-11-05DOI: 10.1016/j.jneuroim.2025.578797
Fudong Shi , zhiyi Wu , Jinyan Yin , Yuzhang Liu , Zuoxu Li , Shimin Zhang
Lumbar disc herniation (LDH) is a prevalent degenerative spinal disorder causing chronic low back pain and sciatica through persistent neuroinflammation and central sensitization. Increasing evidence implicates the CXCL12/CXCR4 signaling axis in these processes, yet its modulation by acupuncture remains unclear. To explore this mechanism, a rat model of LDH was established by autologous nucleus pulposus implantation adjacent to the L5 dorsal root ganglion, and behavioral hypersensitivity was assessed using von Frey and plantar tests. LDH induced marked mechanical and thermal hyperalgesia accompanied by upregulation of CXCL12 and CXCR4 in the spinal dorsal horn. CXCL12 localized mainly to neurons and microglia, while CXCR4 was expressed in neurons, astrocytes, and microglia. Pharmacological blockade of CXCR4 with AMD3100 alleviated hypersensitivity and reduced neuronal and glial activation. Acupuncture similarly increased withdrawal thresholds, inhibited c-Fos, GFAP, and Iba-1 expression, and suppressed TNF-α, IL-1β, and IL-6 levels, whereas exogenous CXCL12 reversed these effects. Acupuncture also inhibited ERK1/2 and NF-κB phosphorylation, and selective inhibition of these pathways with PD98059 or PDTC reproduced its analgesic effects. These findings identify the CXCL12/CXCR4–ERK/NF-κB axis as a critical mediator of LDH-induced neuroinflammation and demonstrate that acupuncture mitigates neuropathic pain by suppressing this signaling pathway and glial activation.
{"title":"Acupuncture mitigates sciatic neuropathic pain in lumbar disc herniation via inhibiting spinal CXCL12/CXCR4-driven glial activation and neuroinflammation","authors":"Fudong Shi , zhiyi Wu , Jinyan Yin , Yuzhang Liu , Zuoxu Li , Shimin Zhang","doi":"10.1016/j.jneuroim.2025.578797","DOIUrl":"10.1016/j.jneuroim.2025.578797","url":null,"abstract":"<div><div>Lumbar disc herniation (LDH) is a prevalent degenerative spinal disorder causing chronic low back pain and sciatica through persistent neuroinflammation and central sensitization. Increasing evidence implicates the CXCL12/CXCR4 signaling axis in these processes, yet its modulation by acupuncture remains unclear. To explore this mechanism, a rat model of LDH was established by autologous nucleus pulposus implantation adjacent to the L5 dorsal root ganglion, and behavioral hypersensitivity was assessed using von Frey and plantar tests. LDH induced marked mechanical and thermal hyperalgesia accompanied by upregulation of CXCL12 and CXCR4 in the spinal dorsal horn. CXCL12 localized mainly to neurons and microglia, while CXCR4 was expressed in neurons, astrocytes, and microglia. Pharmacological blockade of CXCR4 with AMD3100 alleviated hypersensitivity and reduced neuronal and glial activation. Acupuncture similarly increased withdrawal thresholds, inhibited c-Fos, GFAP, and Iba-1 expression, and suppressed TNF-α, IL-1β, and IL-6 levels, whereas exogenous CXCL12 reversed these effects. Acupuncture also inhibited ERK1/2 and NF-κB phosphorylation, and selective inhibition of these pathways with PD98059 or PDTC reproduced its analgesic effects. These findings identify the CXCL12/CXCR4–ERK/NF-κB axis as a critical mediator of LDH-induced neuroinflammation and demonstrate that acupuncture mitigates neuropathic pain by suppressing this signaling pathway and glial activation.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"410 ","pages":"Article 578797"},"PeriodicalIF":2.5,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145504620","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}
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