Suspected Pembrolizumab-Associated Encephalitis Presenting as Altered Mental Status in an Elderly Patient with Cancer: A Case Report

Abstract

Immune checkpoint inhibitors such as pembrolizumab are increasingly used in cancer therapy and are associated with rare but serious immune-related neurological adverse effects, including autoimmune encephalitis.An 83-year-old woman with stage IV non-Hodgkin lymphoma presented with acute altered mental status---confusion, decreased verbal responsiveness, and inability to follow commands---after a single palliative infusion of pembrolizumab, her first and only dose. She had received no prior chemotherapy, radiation, or other systemic oncologic therapy. On examination, she was somnolent but arousable, disoriented and largely nonverbal, with bilateral upper-extremity weakness, reduced right-sided movement and sensation, and mild spasticity.Laboratory studies, neuroimaging, and cerebrospinal fluid (CSF) analysis were performed to evaluate metabolic, infectious, vascular, and structural causes. Several plausible contributors were identified: Klebsiella urinary tract infection, hyponatremia, hypotensive episodes, COVID-19 infection, and a subsequent left thalamic infarction --- but none fully accounted for the prolonged, fluctuating course. Given recent pembrolizumab exposure, inflammatory CSF findings, and negative CSF infectious studies, pembrolizumab-associated encephalitis was suspected.Empiric treatment for suspected infectious causes produced no significant improvement. Intravenous methylprednisolone 75 mg every 12 hours (1.76 mg/kg/day) was started on hospital day 33; within 24--72 hours the patient became increasingly alert and verbal, able to follow commands, with motor function improving toward baseline. No other major diagnostic or therapeutic change occurred during that period. Corticosteroids were transitioned to oral prednisone 40 mg twice daily with a taper at discharge.Suspected pembrolizumab-associated encephalitis should remain in the differential for altered mental status in patients receiving immune checkpoint inhibitors when infectious, metabolic, hemodynamic, and vascular contributors do not fully explain the clinical course, although response to corticosteroids alone does not establish causality.