Uncovering Individualized Cerebellar Atrophy Pattern and Behavioral Links in Children with Brainstem Tumor
BackgroundBrainstem tumors are rare and result in enduring behavioral issues, posing challenges for patients and surgeons. Despite similarities in symptoms to those resulting from cerebellar injuries, limited research has investigated cerebellar changes in patients with brainstem tumors.

MethodsHere, we employed U-Net-based segmentation to analyze the cerebellum in 26 regions, assessing individual volume deviations. Additionally, we developed a behavior prediction model using the total outlier count (tOC) index and brain volume as features.

FindingsOur normative model results revealed that most patients exhibited negative deviation in most cerebellar regions, particularly in lobule Right V, Left I-III, Right X, and Left X. The results found a significant association between a higher tOC and severe social problems (r = 0.31, p = 0.001) and withdrawal behavior (r = 0.28, p = 0.001). Further analysis showed that smaller cerebellar regions correlated strongly with more pronounced social problems (r = 0.27, p = 0.007) and withdrawal behavior (r = 0.25, p = 0.015). Notably, lobules such as Right X, V, IV, and VIIB, along with Left IX, VIII, and X exerted the greatest influence on social problems, whereas regions including Left V, Right IV, and Vermis VI and VIII were most impactful on withdrawal behavior.

InterpretationIn summary, our study revealed cerebellar atrophy patterns in patients with brainstem tumors, emphasizing the role of both anterior and posterior cerebellar lobes in social problems and withdrawal behavior. This research sheds light on the brain mechanisms underlying complex behavioral disorders in brainstem tumor patients.

FundingThis study was supported by the STI2030-Major Projects 2021ZD0200201 and Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes (grant ID: JYY202X-X).

Research in ContextOur previous neuropsychological research has demonstrated that patients with brainstem tumors exhibit a wide range of cognitive and behavioral abnormalities, which closely resemble cerebellar cognitive affective syndrome (CCAS). Dines et al. hypothesized, based on cognitive impairment observed in patients with brainstem injury, that the brainstem, as an integral part of the cerebellar-cortex pathway, plays a role in cognitive processing. Consequently, brainstem injury may lead to cerebellar dysfunction. Previous studies have also reported that gangliocytoma located in the brainstem can cause ipsilateral cerebellar atrophy. These findings suggest that cerebellar injury may be present in patients with brainstem tumors. However, no systematic studies have investigated the pattern of cerebellar injury in these patients and its association with cognitive and behavioral disorders.

Added value of this studyThis study revealed the pattern of cerebellar heterogeneity in patients with brainstem tumors. Further, this study provides evidences for the cerebellums role beyond motor control, underscoring its involvement in complex social behaviors. This study provides insight into automatic cerebellar segmentation algorithm applied to patients dataset.

Implications of all the available evidenceThis study is first to successfully apply machine learning for segmenting deformed cerebellums, providing a reference for future large-sample studies of diseased cerebellum and brainstems. Moreover, this study provides evidence that the brainstem and cerebellum are involved in complex cognitive processing. Future research should focus on developing personalized treatment and rehabilitation programs for patients with brainstem tumors and cerebellar injury to improve their prognosis.