Glymphatic system dysfunction in pediatric growth hormone deficiency evidenced by multiple MRI metrics

The clearance of brain metabolic waste occurs mainly through the glymphatic system. This study aimed to explore the change of glymphatic function in children with growth hormone deficiency (GHD) using non-invasive imaging methods.

This prospective research recruited 40 cases of pediatric GHD and 40 age- and gender-matched typically developing (TD) children. Glymphatic circulation, which includes the production of cerebrospinal fluid (CSF), represented by choroid plexus volume (CPV), influx, evaluated by perivascular space (PVS) burden, and waste clearance, as indirectly assessed by diffusion tensor imaging-based analysis along the perivascular space (DTI-ALPS), was explored for all participants. Partial correlations were conducted between significant magnetic resonance imaging (MRI) metrics and clinical variables in GHD children.

Considering the production of CSF, decreased CPV was presented in pediatric GHD [0.77±0.15 vs. 0.83±0.19 mL; P_{false discovery rate (FDR)}=0.002]. Considering influx, pediatric GHD exhibited lower PVS burden than did TD children (4.51±1.74 vs. 6.30±3.34 mL; P_FDR=0.01). Considering waste clearance, DTI-ALPS decreased significantly in GHD groups (1.35±0.14 vs. 1.49±0.1; P_FDR<0.001). Moreover, in children with GHD, Social Competence scores were positively correlated with PVS volume (r=0.358, P=0.032), PVS/white matter volume (WMV; r=0.420, P=0.010), and PVS/intracranial volume (ICV; r=0.410, P=0.010), whereas Activity Level was negatively correlated with CPV (r=-0.377, P=0.023).

Our findings suggest that glymphatic dysfunction may be a pathological mechanism in pediatric GHD. Furthermore, our study demonstrates that CPV, PVS volume, and DTI-ALPS index could serve as multiple auxiliary biomarkers for assessing the glymphatic function in pediatric GHD.