{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T23:24:40Z","timestamp":1789428280327,"version":"build-2803163510"},"reference-count":14,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"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>Neurological immune-related adverse events (N-irAEs) represent rare but potentially fatal complications of immune checkpoint inhibitor (ICI) therapy. Among these, encephalitis associated with paraneoplatic neuronal antibodies poses a major diagnostic and therapeutic challenge, as it blurs the distinction between drug-induced toxicity and tumor-driven autoimmunity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>We report a 61-year-old male diagnosed with unresectable sarcomatoid pleural mesothelioma who was treated with first-line nivolumab plus ipilimumab. Following the third treatment cycle, the patient developed progressive hyperphagia, central sleep apnea, and autonomic dysfunction. Serum testing revealed strong positivity for anti-Ma2\/Ta antibodies, while brain magnetic resonance imaging was unremarkable. Despite discontinuation of immunotherapy and treatment with high-dose corticosteroids and intravenous immunoglobulin, the patient experienced relentless neurological deterioration. Notably, follow-up positron emission tomography demonstrated complete metabolic tumor response. The patient ultimately died from progressive brainstem dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Anti-Ma2\u2013associated encephalitis is classically categorized as a paraneoplastic neurological syndrome mediated by cytotoxic T-cell responses against intracellular neuronal antigens. Recent evidence suggests that ICIs can unmask or accelerate latent paraneoplastic autoimmunity by amplifying pre-existing immune responses. In this context, our case is best interpreted as an ICI-triggered paraneoplastic neurological syndrome rather than a primary immune-related adverse event.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This case highlights a fatal neurological complication occurring in parallel with complete oncologic remission, underscoring the paradox of effective cancer immunotherapy precipitating catastrophic immune-mediated neurotoxicity. Early recognition of prodromal neurological symptoms and heightened awareness of paraneoplastic syndromes in the ICI era are critical to improving patient outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1739494","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T05:29:25Z","timestamp":1773034165000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Case Report: Immune checkpoint inhibitor\u2013triggered anti-Ma2 paraneoplastic encephalitis in sarcomatoid pleural mesothelioma: a fatal case"],"prefix":"10.3389","volume":"16","author":[{"given":"Ilker Nihat","family":"Okten","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, TC Sa\u011fl\u0131k Bakanl\u0131\u011f\u0131 G\u00f6ztepe Prof. Dr. S\u00fcleyman Yal\u00e7\u0131n City Hospital","place":["Istanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuba","family":"Bayda\u015f","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, TC Sa\u011fl\u0131k Bakanl\u0131\u011f\u0131 G\u00f6ztepe Prof. Dr. S\u00fcleyman Yal\u00e7\u0131n City Hospital","place":["Istanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3239","article-title":"The blockade of immune checkpoints in cancer immunotherapy","volume":"12","author":"Pardoll","year":"2012","journal-title":"Nat Rev Cancer"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1703481","article-title":"Immune-related adverse events associated with immune checkpoint blockade","volume":"378","author":"Postow","year":"2018","journal-title":"N Engl J 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Neurology"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25131","article-title":"Autoimmune encephalitis epidemiology and a comparison to infectious encephalitis","volume":"83","author":"Dubey","year":"2018","journal-title":"Ann Neurology"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2025-335998","article-title":"Neurological immune-related adverse events with checkpoint inhibitor therapy: challenges for the neurologist","volume":"96","author":"Willis","year":"2025","journal-title":"J Neurol Neurosurg Psychiatry"}],"container-title":["Frontiers in 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