Glymphatic system dysfunction in pediatric tourette syndrome Neuroimaging evidence from MRI metrics.

Objective: The glymphatic system, vital for brain waste clearance, is implicated in neurodevelopmental diseases, but its role in pediatric Tourette syndrome (TS) is not well understood. This study investigates structural and functional alterations in the glymphatic system in pediatric TS using non-invasive MRI techniques.

Methods: This case-control study included 37 children with Tourette syndrome (TS) and 37 age- and gender-matched typically developing (TD) controls. We assessed brain volumetric differences and glymphatic function using two MRI metrics: perivascular space (PVS) burden for glymphatic influx and the DTI-ALPS index for waste clearance, with PVS quantified via semi-automated analysis of axial T2-weighted images. Correlations between MRI metrics and clinical symptoms in TS children were analyzed using partial correlations.

Results: Children with Tourette syndrome (TS) exhibited significant reductions in brain parenchymal and white matter volume compared to typically developing (TD) children (all PFDR < 0.001), along with a higher perivascular space (PVS) volume (6.29 ± 3.62 mL vs. 4.76 ± 2.13 mL; PFDR = 0.046), indicating impaired glymphatic influx. The DTI-ALPS index was lower in TS (1.21 ± 0.18 vs. 1.46 ± 0.12; PFDR < 0.001), reflecting reduced waste clearance, and Dzassoc and Dzproj metrics were positively correlated with motor tic severity in TS (all P ≤ 0.02).

Conclusions: Our findings suggest significant glymphatic dysfunction in pediatric TS, indicating its role in the disorder's pathogenesis. Increased PVS burden and decreased DTI-ALPS index may serve as non-invasive biomarkers for diagnosing and understanding TS mechanisms.