Glymphatic Dysfunction Reflects Post-Concussion Symptoms: Changes Within 1 Month and After 3 Months.

OBJECTIVE

Mild traumatic brain injury (mTBI) may alter glymphatic function; however, its progression and variability remain obscure. This study examined glymphatic function following mTBI within 1 month and after 3 months post-injury to determine whether variations in glymphatic function are associated with post-traumatic symptom severity.

METHODS

Glymphatic function was estimated using diffusion tensor image analysis along the perivascular space (DTI-ALPS). This index was measured in 39 individuals with mTBI (47.21 ± 14.88 years) at initial and follow-up assessments, and in 35 age-matched controls (44.62 ± 13.12 years), using manually defined regions of interest at the lateral ventricle level. A linear mixed-effects (LME) model was used to compare ALPS indices among groups. Additional LME analyses evaluated continuous associations between the ALPS index and symptom severity, as assessed by the Rivermead Post-Concussion Symptoms Questionnaire (RPCSQ). Based on ALPS changes, patients were classified into increasing and decreasing subgroups, and comparative analyses of RPCSQ trajectories were conducted.

RESULTS

At baseline, the index did not differ between patients with mTBI and controls; at follow-up, it was significantly lower in the mTBI group. Longitudinal ALPS changes were significantly associated with RPCSQ scores, whereas baseline ALPS showed only a marginal association with initial symptom severity. Individuals in the decreasing ALPS group demonstrated more severe overall symptoms and a slower rate of symptom resolution.

INTERPRETATION: Glymphatic dysfunction, as represented by the ALPS index, may be associated with persistent post-traumatic symptoms. A time-dependent approach incorporating individual recovery trajectories may be essential when assessing glymphatic biomarkers in mTBI.