Prospective observational study of magnetic resonance imaging in anti-CD19 CAR T-cell-associated neurotoxicity

Background: Immune effector cell-associated neurotoxicity syndrome (ICANS) is a frequent and potentially severe complication of anti-CD19 CAR T-cell therapy. Nevertheless, its neuroradiological characterization remains insufficiently defined, as most available evidence stems from retrospective cohorts, heterogeneous imaging protocols, or studies limited to pediatric populations. Methods: We conducted a prospective, monocentric study including adult patients with B-cell lymphoproliferative disorders undergoing anti-CD19 CAR T-cell therapy. All patients underwent a standardized neurological and neuroradiological protocol, with brain MRI performed at screening (15–20 days before CAR T-cell infusion), 60 days, and 12 months after infusion, as well as urgently in the event of ICANS. Brain MRI records were reviewed by a panel of expert neuroradiologists. Results: Of 154 treated patients, 112 were included. ICANS occurred in 34 patients (30.4%); 27 underwent urgent MRI, which showed abnormalities in 11 cases (40.7%). Two distinct radiological patterns emerged. The central variant pattern—characterized by symmetric involvement of thalami, hippocampi, brainstem, and variably the geniculate bodies or corpus callosum—was associated with severe ICANS and acute clinical deterioration, including two cases with diffuse centrum semiovale edema and intracranial hypertension. This pattern resolved in most cases on follow-up imaging. The stroke-like pattern consisted of focal cortico-subcortical white matter lesions, often DWI-restricted, appearing in both ICANS and asymptomatic patients, typically in subacute phases. These lesions persisted as non-enhancing FLAIR abnormalities at follow-up. Conclusions: Serial brain MRI enabled identification of two specific ICANS-related imaging signatures with distinct temporal and radiological characteristics. While overall MRI sensitivity for ICANS remains low, pattern recognition improves diagnostic specificity, supports clinicians in the differential diagnosis, and provides insights into underling pathophysiology.