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Disrupted age-related glymphatic patterns in children with deep gray matter hypoxic-ischemic encephalopathy: a
Alex Mun-Ching Wong1,2, Tiing-Yee Siow3,4, Ming-Chou Chiang4,5
1Neuroradiology, Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital at Linkou, Linkou, Taiwan. alexmcwchop@yahoo.com.
Insights
Hypoxic-ischemic encephalopathy (HIE) impairs glymphatic system function in children, disrupting normal age-related development. This glymphatic dysfunction correlates with poorer functional outcomes in pediatric patients.
Area of Science:
- Neuroscience
- Pediatric Neurology
- Medical Imaging
Background:
- Hypoxic-ischemic encephalopathy (HIE) is a significant cause of pediatric neurological disability.
- Deep gray matter injury in HIE indicates severe brain damage.
- The glymphatic system, crucial for brain fluid exchange, may be affected by HIE.
Purpose of the Study:
- To assess glymphatic system function in children with HIE-induced deep gray matter injury.
- To investigate the relationship between glymphatic function and age in these children.
- To examine the association between glymphatic dysfunction and functional outcomes.
Main Methods:
- Diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) was used.
- 38 normative controls and 25 HIE patients were analyzed.
- ALPS indices were correlated with age and Pediatric Cerebral Performance Category (PCPC) scores.
Main Results:
- ALPS indices were significantly reduced in HIE patients compared to controls, even after age adjustment.
- In controls, ALPS indices showed a positive correlation with age.
- In HIE patients, age-adjusted ALPS indices negatively correlated with PCPC scores, indicating poorer function.
Conclusions:
- HIE disrupts age-related glymphatic system patterns in children.
- Glymphatic system dysfunction in HIE is linked to adverse functional outcomes.
- DTI-ALPS is a valuable tool for assessing glymphatic function in pediatric HIE.
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.
