A Rare Case of Akathisia After Removal of Subdural Hematoma During Treatment for Malignant Pleural Mesothelioma: Akathisia Induced by Brain Injury or Immune Checkpoint Inhibition

Our plain-English summary of A Rare Case of Akathisia After Removal of Subdural Hematoma During Treatment for Malignant Pleural Mesothelioma: Akathisia Induced by Brain Injury or Immune Checkpoint Inhibition, by T. Wada, Y. Yano, E. Miyamoto (Case Reports in Oncological Medicine, 2025).

The study

• Authors: T. Wada, Y. Yano, E. Miyamoto
• Journal: Case Reports in Oncological Medicine
• Published: 2025;2025:8854694
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Akathisia is a movement disorder primarily caused by antipsychotic medications. Although extremely rare, cases caused by immune checkpoint inhibitors or traumatic brain injury have also been reported. We report on the case of an 82-year-old patient with malignant pleural mesothelioma who developed akathisia following subdural hematoma removal and achieved successful symptom control. Three months after receiving nivolumab and ipilimumab, the patient developed incomplete paralysis of the right side of the body. Examination and medical history revealed that a subdural hematoma was the cause of the movement abnormality. Following hematoma removal, the patient became unable to sit still. We suspected the condition as akathisia secondary to traumatic brain injury. Anticholinergic medication successfully controlled the symptoms, allowing treatment for mesothelioma to resume. Neurological immune-related adverse events associated with immune checkpoint inhibitors are often difficult to resolve completely and can lead to discontinuation of cancer treatment. We hope this case report underscores the importance of carefully evaluating the pathophysiology of neurological abnormalities arising during cancer treatment.

Copyright © 2025 Tomomi Wada et al. Case Reports in Oncological Medicine published by John Wiley & Sons Ltd.

In plain English

This article was a case report about one patient, an 82-year-old man with malignant pleural mesothelioma. The article did not describe any asbestos exposure. He received first-line nivolumab and ipilimumab, and his disease progressed after two courses. On admission for second-line treatment, 3 months after his last dose, he had new right arm and leg weakness and incontinence. A brain MRI showed a subdural hematoma (a collection of blood on the brain), which was surgically drained at another hospital. Afterwards he was severely restless, walking around every 2 to 3 minutes and unable to sleep. After mixed delirium was diagnosed, risperidone and then perospirone did not improve his insomnia, agitation or wandering, and signs considered drug-induced parkinsonism appeared. On tiapride he slept 30 minutes to 1 hour, but wandering continued. Interviews suggested the restlessness had begun before any antipsychotics were given, so the authors considered akathisia caused by brain injury. As biperiden was gradually increased, his sleep and inner restlessness improved, and pemetrexed treatment resumed two months after drainage. The authors considered brain damage the cause but could not rule out a link with the immune therapy.

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 82-year-old man with malignant pleural mesothelioma, treated at the National Hospital Organization Osaka Toneyama Medical Center, Japan
• Exposure: Asbestos exposure was not described. The patient had received the immune checkpoint inhibitors nivolumab and ipilimumab (two courses) and developed a subdural hematoma that was surgically drained.
• Main results:
  • On admission for second-line treatment, brain MRI showed a subacute to acute subdural hematoma, and the patient underwent bilateral cranial drainage surgery.
  • After surgery the patient's Glasgow Coma Scale score improved from 11 to 14, but he remained severely restless. At home he walked around every 2 to 3 minutes and could not sleep.
  • The palliative care team diagnosed mixed delirium. Risperidone, a higher risperidone dose and then perospirone did not improve insomnia, agitation or wandering, and signs considered drug-induced parkinsonism from antipsychotic medications appeared.
  • After perospirone was replaced with tiapride, the patient could sleep for 30 minutes to 1 hour, with nighttime delirium and wandering throughout the day. The nocturnal hallucinations took 2 weeks to disappear.
  • Because restlessness and wandering had been present before antipsychotics were used, the authors considered akathisia caused by brain injury. A repeat MRI showed no signs of encephalitis, brain metastasis, or recurrence of blood accumulation.
  • With gradually increased doses of the anticholinergic drug biperiden, the patient's sleep lengthened and his inner agitation improved.
  • Mesothelioma treatment with pemetrexed resumed two months after cranial drainage, and the patient was able to sleep for about 5 hours at night.
• The authors' conclusion: The authors considered the brain damage that caused the subdural hematoma to be the cause of the akathisia, but stated they could not rule out an association with the immune checkpoint inhibitor therapy.
• Limitations the authors state:
  • The authors did not perform detailed investigations such as cerebrospinal fluid analysis or EEG.
  • The authors stated it remains to be confirmed whether stopping biperiden would cause the akathisia to flare up.

Topics

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

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