Paraneoplastic Brachial Amyotrophic Diplegia and Encephalitis With Ma2-IgG During Immune Checkpoint Inhibitor Use for Mesothelioma: A Case Report

Our plain-English summary of Paraneoplastic Brachial Amyotrophic Diplegia and Encephalitis With Ma2-IgG During Immune Checkpoint Inhibitor Use for Mesothelioma: A Case Report, by S.P. Uysal, S. Badihian, K. Toljan, et al (JTO Clinical and Research Reports, 2026).

The study

• Authors: S.P. Uysal, S. Badihian, K. Toljan, N. Andrapalliyal, J. Stevenson, J. Lee, A. Kunchok
• Journal: JTO Clinical and Research Reports
• Published: 2026;7(5):100980
• Type of article: Case report
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Immune checkpoint inhibitors (ICIs) improve cancer survival but can cause neurologic immune-related adverse events. Ma2-IgG-associated paraneoplastic neurologic syndrome typically presents with central nervous system involvement in patients with testicular or lung cancers. We present a case of paraneoplastic brachial amyotrophic diplegia (BAD) associated with Ma2-IgG which developed after ICI.

Case Report: This is a case report of an 86-year-old man with pleural mesothelioma treated with nivolumab and ipilimumab, who presented with progressive, asymmetric weakness of his upper extremities after 5 cycles of ICI. Examination did not reveal associated sensory deficits. Blood creatine kinase level was normal and acetylcholine receptor antibody testing result was negative. Magnetic resonance imaging revealed findings consistent with bilateral frontal temporal lobe encephalitis, but without concurrent cervical cord lesions. Cerebrospinal fluid analysis revealed mild pleocytosis and oligoclonal bands. Ma2-IgG was present in the cerebrospinal fluid (>1:32) and serum (>1:3200). Electrodiagnostic testing revealed diffuse chronic innervation and active denervation changes involving the upper extremities raising concern for a motor neuron disorder. He was diagnosed with having paraneoplastic BAD and encephalitis. A progressive course ensued, despite initial transient improvement with escalation of immunosuppression.

Conclusion: Paraneoplastic BAD is an uncommon paraneoplastic phenomenon that can occur with Ma2-IgG in the setting of ICI use and atypical tumors.

© 2026 The Authors.

In plain English

This case report described one 86-year-old man with pleural mesothelioma who received the immune checkpoint inhibitors nivolumab and ipilimumab. The article does not discuss asbestos. After 5 cycles, the patient developed weakness in the right arm that progressed to weakness of both arms, without sensory loss. Brain MRI showed changes in the insula and mesial temporal lobes on both sides, with enhancement of both amygdalae. Cervical spine MRI showed no cord lesions. Ma2-IgG antibodies were found in the cerebrospinal fluid (greater than 1:32) and in the blood serum (greater than 1:3200). Nerve and muscle testing of the arms showed active denervation and chronic reinnervation, raising concern for a motor neuron disorder. The patient was diagnosed with paraneoplastic limbic encephalitis and brachial amyotrophic diplegia. The checkpoint inhibitors were stopped. A repeat brain MRI improved, but the arm weakness persisted or worsened despite steroids, intravenous immunoglobulin and cyclophosphamide. The patient moved to hospice care because of cancer progression. The authors concluded that checkpoint inhibitors may unmask such syndromes in tumors not typically linked to them, and that this condition should be considered in cancer patients with progressive asymmetric arm weakness.

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 (one patient)
• Who was studied: One 86-year-old man with pleural mesothelioma, diagnosed 8 months before the neurologic symptoms and previously treated with pemetrexed and carboplatin. The article does not state where or when the patient was treated, beyond the authors' Cleveland Clinic and Boston affiliations.
• Exposure: Treatment with the immune checkpoint inhibitors nivolumab and ipilimumab (5 cycles). Asbestos exposure is not mentioned in the article.
• Main results:
  • The patient developed right upper extremity weakness that progressed to left upper extremity weakness and weakness of both arms (diplegia).
  • Sensory, lower extremity and cerebellar examinations were normal.
  • Brain MRI showed hyperintensities in the bilateral insula and mesial temporal lobes with bilateral amygdala enhancement. Cervical MRI showed mild degenerative changes but no cord lesions.
  • Oligoclonal bands were present in the cerebrospinal fluid. Ma2-IgG was positive in the cerebrospinal fluid (greater than 1:32) and serum (greater than 1:3200), both measured by nanoliter scale immunoassay.
  • Electrodiagnostic testing of the arms showed chronic reinnervation and active denervation, which raised concern for a motor neuron disorder. Testing of the left arm at about 3 to 4 months showed severe active denervation and chronic reinnervation across C5 to T1.
  • The patient was diagnosed with immune checkpoint inhibitor-associated paraneoplastic limbic encephalitis and brachial amyotrophic diplegia (BAD).
  • The checkpoint inhibitor was stopped. Treatment was intravenous methylprednisolone (1 g daily for 5 days) followed by a prednisone taper, then 2 g/kg intravenous immunoglobulin at 2 months, then intravenous cyclophosphamide (750 mg/m2).
  • A repeat brain MRI showed interval improvement. However, the right arm weakness worsened despite treatment, and the patient transitioned to hospice care because of cancer progression.
• The authors' conclusion: The authors concluded that paraneoplastic BAD should be considered in cancer patients with progressive asymmetric upper extremity weakness. They also concluded that immune checkpoint inhibitor therapy may unmask paraneoplastic neurologic syndromes in tumors not typically linked to paraneoplastic autoimmunity, noting that mesothelioma is an uncommon cancer associated with Ma2-IgG syndromes.

Topics

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

Related studies

• Case Report: Immune checkpoint inhibitor-triggered anti-Ma2 paraneoplastic encephalitis in sarcomatoid pleural mesothelioma: a fatal case — I.N. Okten, T. Baydaş (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)
• Immune checkpoint inhibitors in non-small cell lung cancer (NSCLC): Approaches on special subgroups and unresolved burning questions — J. Remon, N. Vilariño, et al. (2018)
• Immune checkpoint inhibitor associated reactivation of primary membranous nephropathy responsive to rituximab — J.S. Lin, D.Y. Wang, et al. (2020)
• Current evidence and future perspectives of immune-checkpoint inhibitors in unresectable malignant pleural mesothelioma — K. Hotta, N. Fujimoto (2020)

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