Immunotherapy-associated dysgraphia as an early neurocognitive manifestation of immune effector cell-associated neurotoxicity syndrome: clinical characteristics, mechanistic insights, and assessment challenges.

Background: Immune effector cell therapies, including chimeric antigen receptor T-cell (CAR-T) therapy and T-cell-engaging antibodies, are associated with immune effector cell-associated neurotoxicity syndrome (ICANS), a clinically recognized immune-mediated neurotoxicity. Among its neurological manifestations, writing impairment (dysgraphia), including paligraphia and other forms of writing disturbance, has emerged as a potentially sensitive clinical marker of higher-order cortical dysfunction. Objective: This review synthesizes current clinical evidence on ICANS-associated dysgraphia, characterizes its clinical and neurocognitive features, and examines limitations in existing assessment frameworks. Methods: A structured literature search was conducted using PubMed to identify reports describing writing impairment associated with immune effector cell therapies. Studies were selected through title and abstract screening, with additional relevant reports identified through manual reference screening to address limitations of keyword-based indexing. Results: The available evidence consists primarily of case reports and small series describing early-onset dysgraphia, frequently characterized by paligraphia, spatial disorganization, and executive dysfunction. Writing impairment typically emerges within days of infusion and often occurs during the early phase of ICANS. Although its precise frequency remains unknown, published reports suggest that dysgraphia may be under-recognized rather than truly rare. Importantly, these findings indicate that ICANS-associated dysgraphia represents a heterogeneous spectrum of writing abnormalities that is not adequately captured by current assessment tools such as the ICE score, which rely on binary evaluation. Conclusions: Dysgraphia represents an under-recognized but clinically meaningful manifestation of ICANS and may serve as an early and sensitive indicator of higher-order cortical dysfunction. The development of structured and quantitative handwriting assessment strategies may improve early detection and monitoring of neurotoxicity in patients receiving immunotherapy.