{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:13:59Z","timestamp":1790885639201,"version":"4.1.0"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T00:00:00Z","timestamp":1752710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Immune checkpoint inhibitor (ICI)-associated neurological immune-related adverse events (NAEs) are rare but serious side effects, of which autoimmune encephalitis (AIE) is a potentially fatal central nervous system disorder requiring more attention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a retrospective disproportionality analysis of NAE reports in the FDA Adverse Event Reporting System (FAERS) and the Japanese Adverse Event Reporting Database (JADER) from 2004 to 2024, utilizing reporting odds ratio (ROR), proportional reporting ratio (PRR), the Bayesian confidence propagation neural network BCPNN, and the multi-item gamma Poisson shrinker (MGPS) for signal detection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In total, 3,999 reports of ICI-associated NAEs were identified from the FAERS database, of which 1,998 reports were AIE. 1,558,251 reports of AEs were collected from the JADER database, which contained 890 AIE reports. ICIs, including pembrolizumab, nivolumab, atezolizumab, ipilimumab, and durvalumab, were identified among the top 30 agents in both databases, demonstrating significant signals across all 4 algorithms. Except for noninfectious myelitis, acute disseminated encephalomyelitis, and multiple sclerosis, positive signals were detected in all other preferred terms (PTs). These NAEs accounted for 23.7% of total mortality, with myasthenia gravis (MG) exhibiting the highest mortality rate at 30.63%. Specific PTs, such as aseptic meningitis, AIE, chronic inflammatory demyelinating polyradiculoneuropathy, Guillain-Barr\u00e9 syndrome, MG, myelitis, and immune-related myopathy, were associated with the severity of outcomes, showing significant statistical differences between severe and non-severe cases (p &amp;lt; 0.05).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study found a notable correlation between ICIs and AIE and other specific NAEs, highlighting the demographic characteristics, time to onset, and disease severity of ICI-induced NAEs, thereby facilitating the timely recognition and treatment of these ICI therapy-related complications.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2025.1621045","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T05:25:17Z","timestamp":1752729917000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Immune checkpoint inhibitor-associated autoimmune encephalitis and other neurological immune-mediated adverse events: a pharmacovigilance study using the FAERS and JADER"],"prefix":"10.3389","volume":"15","author":[{"given":"Xiaomeng","family":"Di","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Gai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1186\/s12964-022-00854-y","article-title":"Tumor immunotherapies by immune checkpoint inhibitors (ICIs); the pros and cons","volume":"20","author":"Naimi","year":"2022","journal-title":"Cell Commun Signal CCS"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.113365","article-title":"A comprehensive review of immune checkpoint inhibitors for cancer treatment","volume":"143","author":"Arafat Hossain","year":"2024","journal-title":"Int Immunopharmacol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-020-0160-6","article-title":"Immune-related adverse events of checkpoint inhibitors","volume":"6","author":"Ramos-Casals","year":"2020","journal-title":"Nat Rev Dis Primer"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-022-03997-7","article-title":"Immune-related aseptic meningitis and strategies to manage immune checkpoint inhibitor therapy: A systematic review","volume":"157","author":"Nannini","year":"2022","journal-title":"J Neurooncol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1186\/s12885-018-3997-2","article-title":"Neuromyelitis optica spectrum disorder secondary to treatment with anti-PD-1 antibody nivolumab: The first report","volume":"18","author":"Narumi","year":"2018","journal-title":"BMC Cancer"},{"key":"B6","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1186\/s12883-022-02987-6","article-title":"A case report of neuromyelitis optica spectrum disorder induced by pembrolizumab treatment for lung adenocarcinoma: A clinical and immunohistochemical study","volume":"22","author":"Hirano","year":"2022","journal-title":"BMC Neurol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000200055","article-title":"MOG-IgG-associated demyelination induced by pembrolizumab treatment in a patient with Malignant melanoma","volume":"98","author":"Liu","year":"2022","journal-title":"Neurology"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2025.108265","article-title":"Immune checkpoint inhibitor-related CNS vasculitis - 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