General description

Immune effector cell-associated neurotoxicity syndrome (ICANS) represents a complex neuroinflammatory disorder that occurs following immune effector cell therapies, particularly CAR-T cell therapy. The pathophysiology of ICANS involves multiple interconnected mechanisms that compromise the integrity of the blood-brain barrier and trigger neuroinflammation.

ICANS presents with a characteristic spectrum of neurological symptoms that typically develop within the first week following CAR-T cell infusion, with a median onset of 5-8 days. The clinical presentation follows a stereotypical progression, beginning with mild symptoms and potentially advancing to severe, life-threatening complications.

The initial manifestations of ICANS commonly include aphasia, particularly expressive aphasia affecting object naming, which has been identified as the most specific early sign. Encephalopathy presents as confusion, disorientation, and altered mental status. Patients may experience somnolence, attention deficits, and word-finding difficulties. These symptoms can be subtle initially but progress rapidly.

As ICANS progresses, patients may develop seizures, which can be focal or generalized. The seizures may be brief and self-limited or progress to status epilepticus in severe cases. Hallucinations, both visual and auditory, can occur, along with delirium and mood disturbances. Motor abnormalities may include tremors, myoclonus, asterixis, and in severe cases, focal motor weakness such as hemiparesis or paraparesis.

References

1. Gust, Juliane, et al. "Endothelial activation and blood–brain barrier disruption in neurotoxicity after adoptive immunotherapy with CD19 CAR-T cells." Cancer discovery 7.12 (2017): 1404-1419.