Case report: Diagnosis of impaired consciousness in a cancer patient using immune checkpoint inhibitors

Our plain-English summary of Case report: Diagnosis of impaired consciousness in a cancer patient using immune checkpoint inhibitors, by D. Cathalifaud, C. Basáez, T. Yáñez (Frontiers in Immunology, 2025).

The study

• Authors: D. Cathalifaud, C. Basáez, T. Yáñez
• Journal: Frontiers in Immunology
• Published: 2025;16:1458686
• Type of article: Case report
• Read it: PubMed · Publisher · Free full text

Abstract

Immune checkpoint inhibitors (ICIs) are drugs that are being increasingly used in the field of oncology; due to their mechanism of action, they can present immune-related adverse effects (IRAEs), with various clinical manifestations, one of which is delirium. We present the case of a patient diagnosed with pleural mesothelioma that started combined palliative immunotherapy two months before admission. She was hospitalized for delirium with psychotic symptoms and a comprehensive neurological and etiological examination for this pathology was performed, revealing undetectable TSH levels, indicating the etiology of the condition as thyrotoxicosis in the context of autoimmune thyroiditis, secondary to treatment with ICIs. Symptomatic treatment with beta-blockers was initiated, leading to progressive improvement. This case brings awareness of impaired consciousness and neuropsychiatric symptoms as manifestation of IRAEs and the difficulty of their diagnosis: there may also be several other causes of impaired consciousness, so the characterization of delirium requires a multifaceted approach to determine the underlying cause, taking into account direct cancer-related complications and those stemming from the treatments received by this group of patients. Endocrinological immune-related adverse events (IRAEs), such as thyroid IRAEs, generally have a low lethality rate, do not necessarily require discontinuation of therapy, and are linked to a more favorable oncological prognosis. Conversely, neurological IRAEs, though rare, constitute a contraindication for further use of ICIs. This clinical case emphasizes the importance of the systematic study of consciousness impairment in cancer patients, and of considering multiple IRAEs that could lead to changes in oncological therapy when establishing possible etiologies.

Copyright © 2025 Cathalifaud, Basáez and Yáñez.

In plain English

This is a case report about one patient: a 64-year-old woman with predominantly epithelioid pleural mesothelioma. The article does not discuss asbestos or the cause of her mesothelioma. She had chemotherapy with pemetrexed and cisplatin in 2016-2017. After the disease later progressed, she began palliative immunotherapy with nivolumab and ipilimumab, drugs called immune checkpoint inhibitors. She was admitted to hospital after two months of worsening confusion, disorientation, forgetfulness and occasional night-time hallucinations, which began when the immunotherapy started. A brain MRI showed no spread of the mesothelioma, the EEG (a test of brain electrical activity) was normal, and a lumbar puncture showed no signs of encephalitis. Tests showed suppressed TSH and raised thyroid hormones. The authors concluded that the delirium was caused by thyrotoxicosis (excess thyroid hormone) from autoimmune thyroiditis brought on by the immunotherapy. Beta-blocker treatment led to gradual improvement. The authors noted that follow-up was lost after discharge. They concluded that an organized, multisystem diagnostic approach is crucial in cancer patients on these drugs who develop impaired consciousness.

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 64-year-old female patient with predominantly epithelioid pleural mesothelioma, previously treated with chemotherapy in 2016-2017. The authors are affiliated with Pontificia Universidad Católica de Chile and Hospital Clínico Red de Salud UC-Christus, Santiago, Chile. The date of admission is not stated.
• Exposure: The exposure studied is not asbestos, which the article does not mention. It is palliative combined immunotherapy with the immune checkpoint inhibitors nivolumab 180 mg (3 mg/kg) and ipilimumab 60 mg (1 mg/kg), started after locoregional progression of the mesothelioma.
• Main results:
  • The patient had a 2-month history of progressive disorientation, inattention, forgetfulness, confusion and sporadic nocturnal visual hallucinations. These symptoms began when the immunotherapy started.
  • A mild urinary tract infection was found and treated. The authors stated that it did not explain the range of symptoms.
  • Brain MRI showed no vascular lesions or spread of the mesothelioma. The EEG was normal, and lumbar puncture showed no encephalitis or leptomeningeal spread.
  • TSH was suppressed and total T4 and T3 were elevated. TRAb and anti-TPO antibodies were absent, anti-thyroglobulin antibodies were present, and thyroid iodine uptake was low.
  • The cause of the delirium was judged to be thyrotoxicosis from autoimmune thyroiditis secondary to immune checkpoint inhibitor treatment.
  • Beta-blocker treatment was followed by gradual improvement of the neurological symptoms.
• The authors' conclusion: The authors concluded that impaired consciousness in cancer patients using immune checkpoint inhibitors is a complex diagnostic challenge. In their view, an organized, multisystemic diagnostic approach is crucial to reach the correct diagnosis.
• Limitations the authors state:
  • Follow-up was lost after discharge. There is no information on further symptom resolution or TSH monitoring after immunotherapy resumed.

Topics

Medical terms in this study, explained in our Lexicon: checkpoint inhibitors, Immune-Related Adverse Events, Pleural Mesothelioma, Palliative Care, Immunotherapy, Pathology, Etiology, Prognosis.

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• Pre-treatment high-sensitivity troponin T for the short-term prediction of cardiac outcomes in patients on immune checkpoint inhibitors — S. Petricciuolo, M.G. Delle Donne, et al. (2021)
• Serum cytokines as a biomarker for immune checkpoint inhibitor toxicity in patients with pleural mesothelioma — S.J. Farooqi, Z. Zhao, et al. (2024)
• Celiac Disease After Administration of Immune Checkpoint Inhibitors: A Case Report — J. Leblanc, S. Hoibian, et al. (2021)
• Efficacy of Immune Checkpoint Inhibitors in Rare Tumours: A Systematic Review — F. Petrelli, F. Consoli, et al. (2021)

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