Anti-Ma2-Associated Limbic Encephalitis after Termination of Immune Checkpoint Inhibitor Therapy for Malignant Pleural Mesothelioma

Our plain-English summary of Anti-Ma2-Associated Limbic Encephalitis after Termination of Immune Checkpoint Inhibitor Therapy for Malignant Pleural Mesothelioma, by R. Hashimoto, E. Tanabe, Y. Otsuka, et al (Case Reports in Neurology, 2021).

The study

• Authors: R. Hashimoto, E. Tanabe, Y. Otsuka, Y. Yoneda, Y. Kageyama
• Journal: Case Reports in Neurology
• Published: 2021;13(3):724-728
• Type of article: Case report
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Neurological adverse events of immune checkpoint inhibitor (ICI) therapy mostly develop within 3 months after initiation of ICI treatment. An 82-year-old male with malignant pleural mesothelioma developed anti-Ma2-associated limbic encephalitis at a delay of 18 months after the start of nivolumab therapy (3 months after termination of a 15-month course of ICI treatment). Immunotherapy with steroids and immunoglobulins resulted in moderate neurological improvement. Over the next year, malignant pleural mesothelioma gradually worsened, while the anti-Ma2 antibody test remained positive. Anti-Ma2 paraneoplastic encephalitis may occur after a delay following the discontinuation of ICI therapy.

Copyright © 2021 by S. Karger AG, Basel.

In plain English

This case report, by neurologists at a hospital in Amagasaki, Japan, described an 82-year-old man with biopsy-confirmed stage I malignant pleural mesothelioma. After first-line chemotherapy with carboplatin and pemetrexed, he received 31 courses of the immune checkpoint inhibitor nivolumab over 15 months. When the cancer progressed, he was switched to gemcitabine plus vinorelbine. Eighteen months after his first nivolumab dose, and 3 months after his last, he developed seizures of the right face, memory problems and speech difficulties. His blood tested positive for the anti-Ma2 antibody, brain MRI showed lesions in temporal and frontal regions, and he was diagnosed with anti-Ma2 limbic encephalitis. High-dose steroids improved his cognitive test score from 14/30 to 24/30. Added immunoglobulin brought no further improvement. Chemotherapy was later stopped because of lymph node enlargement. Two months after that, his seizures returned and the antibody was still positive. The authors concluded that this encephalitis may occur even after immune checkpoint inhibitor treatment ends. They stated that they could not scientifically confirm that nivolumab directly caused it. The article does not discuss asbestos exposure.

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 (single patient)
• Who was studied: One 82-year-old man with biopsy-confirmed stage I malignant pleural mesothelioma, reported by the Division of Neurology, Hyogo Prefectural Amagasaki General Medical Center, Japan
• Exposure: The exposure studied was the cancer drug nivolumab, an anti-PD-1 immune checkpoint inhibitor: 31 courses of 240 mg over 15 months as second-line therapy. The article does not mention asbestos or any fiber type.
• Main results:
  • In this patient, neurological symptoms began 18 months after the first nivolumab dose and 3 months after the last dose. They started with right facial seizures and were followed by memory and speech problems.
  • At presentation the patient scored 14/30 on the Mini-Mental State Examination, a test of thinking and memory.
  • Brain MRI showed high-signal lesions in the right mesial temporal and bilateral basal frontal regions.
  • The patient's serum anti-Ma2 antibody was positive, while the other antibodies tested were negative.
  • The patient's testicular ultrasound and tumor marker tests were negative.
  • After high-dose intravenous methylprednisolone, the patient's MMSE score improved to 24/30.
  • Additional intravenous immunoglobulin produced no further improvement in the patient.
  • After 6 more courses of gemcitabine and vinorelbine over 9 months, chemotherapy was stopped because of right hilar lymph node enlargement. Two months later the patient had seizures again, and his serum anti-Ma2 antibody remained positive.
  • After 1 further steroid session the patient had no more seizures and was discharged with a modified Rankin Scale score of 3.
• The authors' conclusion: The authors concluded that autoimmune anti-Ma2 paraneoplastic encephalitis may occur even after immune checkpoint inhibitor treatment has ended. They suggested that prolonged nivolumab treatment overlapping with refractory mesothelioma may have had a cumulative effect.
• Limitations the authors state:
  • The authors stated that they could not scientifically confirm whether nivolumab was directly linked to the encephalitis.
  • No blood samples from before nivolumab therapy were available, so the authors could not tell whether the antibody was already present.
  • The cerebrospinal fluid was not tested for anti-Ma2 antibodies.

Topics

Medical terms in this study, explained in our Lexicon: checkpoint inhibitors, Pleural Mesothelioma, Nivolumab (Opdivo), Immunotherapy.

Related studies

• Increased frequency of anti-Ma2 encephalitis associated with immune checkpoint inhibitors — A. Vogrig, M. Fouret, et al. (2019)
• Case Report: Immune checkpoint inhibitor-triggered anti-Ma2 paraneoplastic encephalitis in sarcomatoid pleural mesothelioma: a fatal case — I.N. Okten, T. Baydaş (2026)
• 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)
• Dysautonomia and dysosmia associated with anti-Hu antibodies induced by immune checkpoint inhibitors: a case report — M. Fujimoto, K. Igari, et al. (2026)
• Pre-treatment soluble PD-L1 as a predictor of overall survival for immune checkpoint inhibitor therapy: a systematic review and meta-analysis — Á. Széles, T. Fazekas, et al. (2023)
• Response to Immune Checkpoint Inhibitor Therapy in Patients with Unresectable Recurrent Malignant Pleural Mesothelioma Shown by FDG-PET and CT — K. Kitajima, M. Maruyama, et al. (2021)

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