Glymphatic dysfunction in classical trigeminal neuralgia: DTI-ALPS index stratification from healthy controls to post-MVD.

Background: The diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index is a non-invasive marker of glymphatic function. Its relevance in classical trigeminal neuralgia (CTN), postoperative glymphatic changes after microvascular decompression (MVD), and associations with clinical and structural measures remain unclear. This study aimed to evaluate glymphatic dysfunction in CTN, examine postoperative DTI-ALPS alterations, explore correlations with clinical indicators, and assess relationships with hippocampal, amygdala, and ventricular volumes.

Methods: Fifty-three unilateral CTN patients undergoing MVD and 47 age- and sex-matched healthy controls (HCs) underwent 3.0 T MRI including DTI and 3D T1-weighted imaging. The DTI-ALPS indices were computed preoperatively and at the 6-month follow-up, with volumes of the bilateral hippocampi, amygdalae, and lateral ventricles also being determined. Clinical variables included pain severity (VAS, BNI scales), neurovascular compression (NVC) grades, disease duration, carbamazepine dosage, psychological status (PHQ-9, GAD-7), and sleep quality (PSQI). Statistical methods included independent and paired t-tests, Pearson's and Spearman's correlation analyses, multivariate regression, and ROC curve analysis.

Results: Preoperatively, CTN patients showed significantly lower DTI-ALPS indices compared to healthy controls (HCs) on the left, right, and whole-brain (all p < 0.05). Six months post-MVD, only right-side indices remained reduced (p = 0.044). CTN patients also had smaller hippocampal and amygdala volumes and enlarged lateral ventricles versus HCs (all p < 0.05), with no postoperative recovery (all p > 0.05). Preoperative whole-brain DTI-ALPS indices positively correlated with hippocampal volumes and negatively with lateral ventricular volumes. Multivariate regression identified older age and female sex as predictors of lower DTI-ALPS index. ROC analysis indicated preliminary diagnostic potential for distinguishing CTN from HCs (AUC = 0.609, sensitivity/specificity = 83%).

Conclusions: CTN is characterized by persistent glymphatic impairment and structural atrophy-hippocampal and amygdala volume loss with ventricular enlargement-that do not normalize at 6 months post-MVD. Older age and female sex are key modulators of glymphatic dysfunction, while classic clinical indicators show no correlation. Combined DTI-ALPS and volumetric MRI metrics may serve as biomarkers for central nervous system involvement and long-term monitoring in CTN.