Disrupted age-related glymphatic patterns in children with deep gray matter hypoxic-ischemic encephalopathy: a diffusion tensor imaging analysis along the perivascular space study.

PURPOSE: Hypoxic-ischemic encephalopathy (HIE) remains a major cause of pediatric morbidity, with deep gray matter injury reflecting a severe pattern. The glymphatic system, a brain-wide perivascular network facilitating cerebrospinal and interstitial fluid exchange, may be vulnerable to disruption after HIE. We assessed glymphatic function in children with HIE-induced deep gray matter injury using diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) and examined age-related patterns in glymphatic function.

METHODS: DTI-ALPS analysis was retrospectively studied in 38 normative controls (mean ± SD, 26.94 ± 34.03 months) and 25 patients with HIE and deep gray matter injury (20.55 ± 32.49 months). Bilateral ALPS indices were calculated and correlated with age and pediatric cerebral performance category scale (PCPC) scores. Due to non-normal distributions, Spearman correlations and generalized linear models (Gamma distribution, log link) adjusted for age were used for group comparisons. Age-adjusted associations were evaluated using residual-based analyses.

RESULTS: ALPS indices were significantly reduced in HIE patients compared to controls after age adjustment (Left: adjusted difference = 0.248, p < 0.001; Right: adjusted difference = 0.228, p < 0.001). In controls, ALPS indices positively correlated with age (Left: ρ = 0.730, p < 0.001; Right: ρ = 0.615, p < 0.001). After controlling for age using residual-based analyses, ALPS indices in patients negatively correlated with PCPC scores (Left: ρ = -0.468, p = 0.018; Right: ρ = -0.458, p = 0.021).

CONCLUSION: HIE disrupts normal age-related glymphatic patterns, and glymphatic dysfunction is associated with adverse functional outcomes.