Investigation of glymphatic system function in radiologically isolated syndrome

Radiologically Isolated Syndrome (RIS) represents an early radiological manifestation within the Multiple Sclerosis (MS) spectrum, underscoring the critical need for biomarkers to predict disease progression. While glymphatic system (GS) dysfunction is implicated in established MS, its status in the RIS stage remains unclear. The Diffusion Tensor Imaging Analysis Along the Perivascular Space (DTI-ALPS) index is a non-invasive MRI proxy for evaluating perivascular diffusion characteristics.

To investigate glymphatic function in RIS compared to Relapsing-Remitting MS (RRMS) and healthy controls (HC), and to evaluate the DTI-ALPS index as a potential differentiator between RIS and MS.

This prospective cross-sectional study enrolled 46 participants: 15 RIS (mean age 36.7 ± 5.3), 15 RRMS (33.5 ± 5.7), and 16 HC (33.1 ± 4.7). All underwent 3 T brain MRI including Diffusion Tensor Imaging. DTI-ALPS indices were calculated using an automated script with spherical ROIs. Group comparisons were performed using Analysis of Covariance (ANCOVA) to adjust for age and sex.

After adjusting for covariates, DTI-ALPS indices were significantly lower in RRMS patients compared to HCs (p = 0.001) and significantly lower compared to RIS patients (p = 0.043). RIS patients showed no significant difference from HCs (p = 0.266), indicating relatively preserved glymphatic function. Mean DTI-ALPS demonstrated potential in distinguishing RRMS from HCs (AUC=0.804, 95% CI: 0.64-0.96).

Glymphatic function appears preserved in RIS but is significantly impaired in established RRMS. The DTI-ALPS index demonstrates potential to distinguish MS from the RIS, suggesting that glymphatic impairment may be a feature associated with the transition to the clinical disease phase.