Abstract
Background/Objectives: Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment of hematologic malignancies, achieving durable remissions in cases refractory to standard therapies. A potentially life-threatening complication is immune effector cell-associated neurotoxicity syndrome (ICANS), which poses significant challenges to clinical management. ICANS encompasses a range of neuropsychiatric symptoms, including delirium, mood disorders, psychosis, seizures, and cerebral edema. The psychiatric dimensions of ICANS remain underreported, and their interplay with neurologic manifestations is poorly understood. This study reviews the psychiatric manifestations of ICANS and presents a case series illustrating its clinical complexity. Methods: A systematic literature search was conducted using PubMed and Google Scholar for studies published between 2020 and 2024. Search terms included “ICANS”, “delirium”, “CAR T-cell”, “neurotoxicity”, and “psychiatric”. The inclusion criteria included studies published in English that focused on adult patients experiencing neuropsychiatric symptoms of ICANS. Two clinical cases of ICANS with prominent psychiatric features are presented. Results: The literature review found three relevant studies, which emphasized agitation, hypoactivity, and mood disturbances as often-overlooked psychiatric symptoms linked to ICANS. The case series highlights psychiatric manifestations, including delirium, irritability, and cognitive impairment. Recovery was supported through interventions such as corticosteroid tapering, antipsychotic treatment, and multidisciplinary care. Conclusions: ICANS is a multifaceted syndrome with significant neuropsychiatric sequelae that complicate its diagnosis and management. An enhanced recognition of its psychiatric dimensions and interdisciplinary approaches are critical to improving outcomes.