University of Wisconsin–Madison Medical College of Wisconsin

Case Report of Delayed Encephalopathy From Pembrolizumab

Christopher Kotsis, MD; Brandon H. Hidaka, MD, PhD

WMJ. 2025;124(2):173-175

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ABSTRACT

Introduction: Pembrolizumab is an immune checkpoint inhibitor (ICI) used to treat many types of advanced cancer. ICIs can cause encephalopathy, a severe immune-related adverse event, which is a diagnosis of exclusion. Pembrolizumab immune-related adverse events typically develop early (within a few months) in treatment; presentation after a year is extremely rare.

Case Presentation: A 70-year-old White female with metastatic endometrial cancer treated with pembrolizumab for 19 months presented with generalized weakness that rapidly progressed to confusion, delusions, and hallucinations.

Discussion: After ruling out other causes of encephalopathy via broad-based testing of blood and cerebrospinal fluid and imaging, her neurologic status improved after treatment with high-dose glucocorticoids and intravenous immunoglobulin.

Conclusions: Pembrolizumab is an ICI that can cause encephalopathy, which is challenging to diagnose. While immune-related adverse events typically emerge soon after starting treatment, pembrolizumab-induced encephalopathy can be delayed significantly.


Author Affiliations: Mayo Clinic Health System, Eau Claire, Eau Claire, Wisconsin (Kotsis, Hidaka).
Corresponding Author: Christopher Kotsis, MD, Mayo Clinic Family Medicine Residency, 1400 Bellinger St, Eau Claire, WI 54703; email Kotsis.Christopher@mayo.edu; ORCID ID 0009-0002-7442-1679
Funding/Support: None declared.
Financial Disclosures: None declared.
Acknowledgements: Written informed consent to participate in this case report was obtained from patient’s husband, who is the patient’s surviving spouse. The authors wish to thank their colleagues on the multidisciplinary health care team who provided invaluable expertise.
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