Case Report: Immune checkpoint inhibitor-triggered anti-Ma2 paraneoplastic encephalitis in sarcomatoid pleural mesothelioma: a fatal case

Our plain-English summary of Case Report: Immune checkpoint inhibitor-triggered anti-Ma2 paraneoplastic encephalitis in sarcomatoid pleural mesothelioma: a fatal case, by I.N. Okten, T. Baydaş (Frontiers in Oncology, 2026).

The study

• Authors: I.N. Okten, T. Baydaş
• Journal: Frontiers in Oncology
• Published: 2026;16:1739494
• Type of article: Case report
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: 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.

Case Presentation: 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.

Discussion: Anti-Ma2-associated 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.

Conclusion: 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.

Copyright © 2026 Okten and Baydaş.

In plain English

This case report described one 61-year-old man with sarcomatoid pleural mesothelioma, diagnosed in February 2024 and judged unresectable. The article does not discuss asbestos exposure. From March 2024 he received six cycles of immunotherapy: nivolumab plus ipilimumab in cycles 1 and 4, and nivolumab alone in cycles 2, 3, 5 and 6. From the fourth cycle onward he developed loud snoring, daytime sleepiness, sudden overeating with weight gain, and episodes of central sleep apnea. In June 2024 he developed urinary retention and autonomic dysfunction and was admitted to intensive care. A brain MRI showed no structural abnormality. A blood test was strongly positive for anti-Ma2/Ta antibodies. Cerebrospinal fluid analysis was not available. Immunotherapy was stopped, and corticosteroids and intravenous immunoglobulin gave only brief benefit. A PET-CT scan in August 2024 showed complete metabolic response of the pleural tumor. He died in February 2025 from progressive brainstem dysfunction, with no evidence of active cancer. The authors concluded that this encephalitis should be regarded as an immunotherapy-triggered paraneoplastic neurological syndrome rather than a primary immune-related adverse event.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Case report of a single patient
• Who was studied: One 61-year-old man with no known neurological history, diagnosed by biopsy with sarcomatoid pleural mesothelioma (stage IIIB, unresectable) in February 2024. The authors are from a medical oncology department in Istanbul, Türkiye.
• Exposure: The exposure examined was immune checkpoint inhibitor therapy, not asbestos. The article does not mention asbestos exposure. Treatment was nivolumab plus ipilimumab at cycles 1 and 4 and nivolumab alone at cycles 2, 3, 5 and 6, given from 15 March to 31 May 2024 following the CheckMate-743 protocol.
• Main results:
  • The patient's neurological symptoms began during treatment. Loud nocturnal snoring started during the fourth cycle and excessive daytime somnolence after the fifth.
  • After the sixth cycle the patient developed rapid-onset hyperphagia (overeating), weight gain and episodes of central sleep apnea. On 4 June 2024 he developed acute urinary retention and autonomic dysfunction and was admitted to intensive care.
  • A brain MRI on 4 June 2024 showed no metastasis, infarction or structural abnormality.
  • Serum immunoblot testing was strongly positive (3+) for anti-Ma2/Ta antibodies. All other paraneoplastic and limbic encephalitis antibodies tested were negative.
  • Immunotherapy was permanently stopped after cycle six. Oral corticosteroids gave no improvement. Intravenous methylprednisolone pulse therapy and intravenous immunoglobulin (total dose 45 g) gave only transient benefit.
  • A PET-CT on 16 August 2024 showed complete metabolic response of the pleural disease, despite ongoing neurological deterioration.
  • The patient died on 16 February 2025 from progressive brainstem dysfunction. At death there was no radiological or clinical evidence of active malignancy.
• The authors' conclusion: The authors concluded that the case supports regarding anti-Ma2-associated encephalitis in the immunotherapy era as a paraneoplastic neurological syndrome triggered by immune checkpoint inhibitors, rather than as a primary immune-related adverse event.
• Limitations the authors state:
  • Antibody testing was done on serum only, by a commercial immunoblot. Cerebrospinal fluid analysis was not available.

Topics

Medical terms in this study, explained in our Lexicon: checkpoint inhibitors, Sarcomatoid, Pleural Mesothelioma, Immune-Related Adverse Events, Unresectable, Nivolumab (Opdivo), Ipilimumab (Yervoy), Immunotherapy.

Related studies

• Paraneoplastic Brachial Amyotrophic Diplegia and Encephalitis With Ma2-IgG During Immune Checkpoint Inhibitor Use for Mesothelioma: A Case Report — S.P. Uysal, S. Badihian, et al. (2026)
• Increased frequency of anti-Ma2 encephalitis associated with immune checkpoint inhibitors — A. Vogrig, M. Fouret, et al. (2019)
• Anti-Ma2-Associated Limbic Encephalitis after Termination of Immune Checkpoint Inhibitor Therapy for Malignant Pleural Mesothelioma — R. Hashimoto, E. Tanabe, et al. (2021)
• Fatal Anti-Ma2 Encephalitis Related to Treatment of Malignant Pleural Mesothelioma With a Combination of Anti-Programmed Death 1 and Anti-Cytotoxic T-Lymphocyte Associated Protein 4 Antibodies — P. Du Rusquec, A. Peyre, et al. (2019)
• Preliminary study highlights the potential of immune checkpoint inhibitors in sarcomatoid mesothelioma — N.K. Brockwell, M. Alamgeer, et al. (2020)
• Dysautonomia and dysosmia associated with anti-Hu antibodies induced by immune checkpoint inhibitors: a case report — M. Fujimoto, K. Igari, et al. (2026)

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