The finding:
This is a review article summarizing neurological side effects of CAR-T cell therapy. Most common being immune effector cell-associated neurotoxicity syndrome (ICANS), acute and usually reversible encephalopathy. It presents within 10 days of treatment with confusion, language impairment, seizures, or cerebral edema. It is driven by systemic cytokine surge and blood-brain barrier (BBB) dysfunction. In patients treated for CNS malignancies, site-specific inflammation can produce Tumor inflammation-associated neurotoxicity (TIAN), driven from inflammatory edema or neuronal-immune interactions at the tumor site. It is characterized by focal deficits, hydrocephalus, or herniation.  Finally, some BCMA-targeting CAR-T therapies are linked to delayed complications such as cranial nerve palsies, and Parkinsonism-like syndrome. Management relies on supportive care, steroids, cytokine inhibitors (IL-1 or IL-6 blockade). Novel designs aim to abruptly diminish the number of circulating CAR T cells either by incorporating “suicide switches” that are inducible, or truncated targetable receptors, which could be targeted by monoclonal antibodies in case of severe toxicities. Onset of these novel strategies appears to be slow, limiting the efficacy in patients requiring immediate reversal.

Strengths:
The clarify of classification helps us develop a clinical conceptual framework. It provides a concise summary of current theories on the pathophysiology related to CAR T side effects, clinical correlations, and treatment approaches.

Weaknesses:
It’s a narrative format, evidence weighting, and risk of bias are not explicitly addressed. Many recommendations are drawn from retrospective series, leaving gaps in evidence-based practice.

Relevance:
The inpatient psycho-oncologist will likely receive consults for encephalopathy secondary to CAR T therapies. Getting a good understanding of the typical neuropsychiatric syndromes related to it is important to provide appropriate recommendations to the primary team.