Workup of Encephalopathy in Patients Receiving Cancer Immunotherapy

Abstract: Cancer immunotherapy has transformed many areas of oncologic care. Neurological immune-related adverse events, particularly encephalopathy, represent potentially life-threatening complications requiring prompt recognition and intervention. Encephalopathic syndromes occur across immunotherapy modalities, including immune checkpoint inhibitors, chimeric antigen receptor-T cell therapy, and bispecific antibodies. The diagnostic challenge lies in distinguishing immune-mediated neurotoxicity from infection, metabolic derangements, disease progression, and paraneoplastic syndromes. A systematic evaluation incorporates detailed clinical assessment with neuroimaging, cerebrospinal fluid analysis, electroencephalography, and autoimmune antibody testing as appropriate. This review provides a practical approach to recognizing and assessing encephalopathy in patients receiving immunotherapy. Early multidisciplinary collaboration between neurology and oncology teams is critical for recognizing symptoms, managing adverse effects, and guiding cancer-directed treatment.