Immune effector cell-associated neurotoxicity syndrome: what the intensivist needs to know

Immune effector cell-associated neurotoxicity syndrome (ICANS) is a significant complication of chimeric antigen receptor T-cell (CAR-T) therapy, a revolutionary treatment for hematologic malignancies. This syndrome, which might affect approximately 30% of CAR-T therapy recipients, presents a wide spectrum of neurological symptoms, ranging from mild confusion to life-threatening cerebral edema. In the intensive care unit (ICU), managing ICANS is critical due to its potential severity. Pathophysiology of ICANS is driven by immune-mediated inflammation disrupting the blood-brain barrier, resulting in cerebral cytokine infiltration and glial cell activation. Its severity is associated with elevated cytokine levels in cerebrospinal fluid and serum, which points to the need for specific biomarkers and predictive tools. Standardized assessments, including the Immune Effector Cell-Associated Encephalopathy (ICE) Score, together with brain imaging and adjunctive diagnostic tests, provide clinicians with essential baseline information for the assessment and monitoring of neurological complications. ICU management focuses on supportive care and pharmacologic strategies. Corticosteroids represent the cornerstone of treatment, effectively targeting neuroinflammation while preserving the antitumor efficacy of CAR-T cell therapy. Anticonvulsants, hyperosmolar agents and advanced neurocritical care measures are also pivotal. Recent advances suggest potential benefits of alternative therapies, such as anti-cytokine agents and innovative immune cell products with reduced neurotoxic risks. Despite advancements, challenges persist, including diagnostic ambiguities, resource allocation, and variability in care protocols. This review highlighted challenges in ICANS management for ICU physicians, intending to underline the importance of early detection, rigorous monitoring, and tailored interventions to improve patient outcomes.