Alterations in the coupling between glymphatic function and cortical morphology in children with short stature

To investigate the functional changes in the glymphatic system and cortical morphological features in children with growth hormone deficiency (GHD) and idiopathic short stature (ISS).

In this prospective study, we recruited 28 children with GHD, 89 children with ISS, and 35 age- and sex-matched typically developing (TD) children. The glymphatic system was evaluated using diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index, preprocessed with FMRIB Software Library. Cortical morphological features (sulcal depth, cortical curvature, and cortical thickness) were extracted from three-dimensional T1- weighted magnetization prepared rapid gradient echo (3D-T1 MPRAGE) imaging, preprocessed with fMRIPrep (v1.5.3), and surface reconstruction was performed using FreeSurfer (version 6.0.0). One-way analysis of variance was used for comparisons between multiple groups. Independent-samples t-test and Pearson's correlation analyses were performed, with Bonferroni or false discovery rate corrected-p value.

In comparison with the TD group, the GHD group showed significantly lower DTI-ALPS indexes (p < 0.05). The left-hemisphere and mean DTI-ALPS indexes were significantly lower in the ISS group than in the TD group (p < 0.05). Children with ISS had smaller brain volumes than TD children (1429.07 ± 128.14 vs. 1489.96 ± 122.72; p < 0.05), whereas the brain volume in children with GHD (1467.16 ± 117.28) was not significantly different from that in TD children (p > 0.05). The ISS and GHD groups showed no significant differences in brain volume. With age-related growth, the children with ISS showed more cortical-area changes in cortical curvature, sulcal depth, and thickness than those in the GHD and TD groups. Cortical morphological features in ISS were intermediate between the GHD and TD groups. Sulcal depth correlated with DTI-ALPS indexes primarily in the peripheral regions of the central sulci in the ISS and TD groups, as well as in the combined cohort. In children with GHD, no significant correlations were observed between the DTI-ALPS indexes and cortical morphological features.

Glymphatic function and development failed in children with short stature. Notably, the coupling between glymphatic function and cortical morphology was absent in children with GHD and enhanced in children with ISS. These findings indicate that the CNS developmental patterns differ between children with GHD and those with ISS and imply that the ISS is not an appropriate control group for GHD in CNS research.