Emotional-Behavioral Dysregulation and Cortical Alterations in Pediatric Diffuse Midline Glioma With H3K27M Mutant: A Case-Control Study

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BACKGROUND AND OBJECTIVES: Emotional-behavioral dysregulation (EBD) significantly affects the quality of life of glioma patients, but few studies report their psychopathological state and related cortical changes in children with diffuse midline gliomas (DMGs) with H3K27M mutant, hindering the implementation of interventions. We aim to explore the relationships among H3K27M mutation, EBD, and cortical remodeling. METHODS: In total, 133 children were enrolled in Beijing during 2019-2024, including 66 children with DMGs with H3K27M mutant (DMGs-HM), 17 DMGs with H3K27M wild type (DMGs-HW), alongside 50 healthy controls (HCs). Multimodal data acquisition included T1-weighted magnetic resonance imaging and Child Behavior Checklist (CBCL) assessments. Cortical morphology was analyzed using surface-based morphometry in Computational Anatomy Toolbox 12. Psychopathological and cortical differences between patients and HCs were analyzed using the Mann-Whitney U test and 2-sample t test. Multiple regression analysis was conducted to examine the correlation between psychopathological outcomes and cortical morphology in patients. RESULTS: Significant differences were observed in total problems CBCL and most subscales between DMGs and HCs. DMGs-HM exhibited significantly higher scores than DMGs-HW in total problems CBCL ( P = .02), attention problems ( P = .01), aggressive behaviors ( P = .033), and thought problems ( P = .017). Surface-based morphometry revealed extensive cortical abnormalities in thickness and complexity in DMGs vs HCs. Brain regions, including the right inferior parietal cortex and the left isthmus-cingulate cortex, were associated with attention problems and aggressive behaviors in DMGs-HM. CONCLUSION: Children with DMGs may present with EBD and cortical alterations. DMGs-HM showed a nonsignificantly higher EBD prevalence than DMGs-HW. The reorganization of specific brain regions correlated with EBD in DMGs-HM. These findings enhance clinical insights into comprehensive diagnosis and personalized treatment, while advancing mental health care for pediatric DMGs.

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