Immune checkpoint inhibitor–induced encephalitis in endometrial carcinoma: Distinguishing immune from infectious causes

Background: Immune checkpoint inhibitors (ICIs) have expanded therapeutic options for advanced gynecologic cancers but can occasionally cause neurologic immune-mediated adverse events such as encephalitis. These presentations can overlap with infectious or metabolic conditions necessitating timely recognition. Case: A 68-year-old woman with stage IIIC1 endometrioid endometrial carcinoma developed progressive encephalopathy 15 days after her fourth cycle of pembrolizumab-based therapy. Initial findings of fever, leukocytosis, and abnormal urinalysis supported urosepsis, and a positive West Nile virus IgM serology further complicated the diagnosis. However, subsequent cerebrospinal fluid studies did not support neuroinvasive West Nile disease. Concurrent severe hypothyroidism further complicated the diagnostic evaluation. Ultimately, negative cerebrospinal fluid cultures, lack of evidence for neuroinvasive disease, and continued neurologic decline despite antimicrobial therapy raised concern for pembrolizumab-induced encephalitis. High-dose intravenous methylprednisolone led to rapid and sustained neurologic improvement, substantiating an immune-mediated etiology. Discussion and conclusion: This case highlights the diagnostic complexity of pembrolizumab-associated encephalitis in the presence of concurrent infectious and endocrine abnormalities. The temporal relationship to immunotherapy, lack of infectious findings, and fast response to corticosteroid treatment were consistent with an immune-mediated etiology. Early recognition of these adverse events is critical to recovery and bolsters the need for a high index of suspicion with these therapies.