Cytokine storm-associated encephalopathies

Background and Aims: Cytokine storm-associated encephalopathies arise in response to severe inflammatory conditions and include neurotoxicity related to CAR-T cell therapy (ICANS), neuro-COVID, and febrile infection-related epilepsy syndrome (FIRES). This PhD research explores key biomarkers and clinical manifestations associated with each of these disorders, focusing on the roles of EEG in predicting ICANS, S100B and neurofilament light chain (NfL) in neuro-COVID, and anatomo-electroclinical features in FIRES. Methods: a prospective cohort of CAR-T recipients was assessed with a standardized protocol, involving EEGs recorded before and after infusion to investigate their predictive value for ICANS. For neuro-COVID, S100B and NfL serum levels were analyzed in COVID-19 patients with and without neurological symptoms to assess their diagnostic and prognostic utility. FIRES cases were evaluated to characterize clinical and investigative features. Results: among 68 CAR-T therapy patients, 22 (32%) developed ICANS, the majority of whom had features consistent with a frontal-lobe encephalopathy; two died due to fulminant cerebral edema. EEG abnormalities, particularly theta and delta slowing, were predictive of ICANS. In 279 COVID-19 patients, elevated NfL levels corresponded with Neuro-COVID disease severity, whereas S100B results were less consistent. Four FIRES patients had anatomo-electroclinical features consistent with neuroinflammation and was associated with secondary sclerosing cholangitis in critically ill patients. Discussion: this research highlights the significance of identifying biomarkers and electroclinical features in cytokine storm-associated encephalopathies and lays the groundwork for translational studies aiming to apply diagnostic and therapeutic findings across these syndromes. Future research should prioritize validation of multi-biomarker panels and cross-condition comparisons.