Therapeutic advances in neurological disorders · 2026
Glymphatic dysfunction in drug-resistant epilepsy and its association with vagus nerve stimulation outcomes: a DTI-ALPS study.
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Xu Ziao, Wang Xiaofeng, Liu Bohang, Ji Xuefei, Shan Ming, Cheng Hongwei, Ye Lei
Аннотация
BACKGROUND: The glymphatic system (GS) is critical for interstitial fluid clearance and has been implicated in various neurological disorders. However, its role in drug-resistant epilepsy (DRE) and response to vagus nerve stimulation (VNS) remains unclear.
OBJECTIVES: This study aimed to assess GS function in patients with DRE using diffusion tensor image analysis along the perivascular space (DTI-ALPS) and to explore its association with VNS outcomes.
DESIGN: Data from patients with DRE who underwent VNS were retrospectively analyzed at a single center.
METHODS: Forty patients with DRE and 30 healthy controls were enrolled. ALPS indices were calculated for the left (ALPS-L), right (ALPS-R), and bilateral (ALPS-B) hemispheres. The clinical outcomes after VNS were classified using McHugh outcome classification. Statistical comparisons and logistic regression were used to examine group differences and the predictive value of ALPS indices.
RESULTS: Compared to controls, patients with DRE exhibited significantly reduced ALPS-L (p < 0.001) and ALPS-B (p = 0.005) indices. Among patients with DRE, responders to VNS had significantly higher ALPS-R (p = 0.021) and ALPS-B (p = 0.027) indices than nonresponders. ALPS-L exhibited a positive trend (p = 0.073). In logistic regression analyses, ALPS-R and ALPS-B were significantly associated with favorable VNS outcomes in univariate and multivariate models. After adjusting for age, sex, and disease duration, ALPS-L (p = 0.028, odds ratio (OR) = 2.739), ALPS-R (p = 0.020, OR = 2.802), and ALPS-B (p = 0.020, OR = 3.241) all emerged as independent predictors of VNS response.
CONCLUSION: Glymphatic dysfunction is present in DRE and may influence responsiveness to VNS. Higher ALPS indices predicted better treatment outcomes, supporting ALPS potential as a noninvasive imaging biomarker for presurgical stratification in epilepsy.
OBJECTIVES: This study aimed to assess GS function in patients with DRE using diffusion tensor image analysis along the perivascular space (DTI-ALPS) and to explore its association with VNS outcomes.
DESIGN: Data from patients with DRE who underwent VNS were retrospectively analyzed at a single center.
METHODS: Forty patients with DRE and 30 healthy controls were enrolled. ALPS indices were calculated for the left (ALPS-L), right (ALPS-R), and bilateral (ALPS-B) hemispheres. The clinical outcomes after VNS were classified using McHugh outcome classification. Statistical comparisons and logistic regression were used to examine group differences and the predictive value of ALPS indices.
RESULTS: Compared to controls, patients with DRE exhibited significantly reduced ALPS-L (p < 0.001) and ALPS-B (p = 0.005) indices. Among patients with DRE, responders to VNS had significantly higher ALPS-R (p = 0.021) and ALPS-B (p = 0.027) indices than nonresponders. ALPS-L exhibited a positive trend (p = 0.073). In logistic regression analyses, ALPS-R and ALPS-B were significantly associated with favorable VNS outcomes in univariate and multivariate models. After adjusting for age, sex, and disease duration, ALPS-L (p = 0.028, odds ratio (OR) = 2.739), ALPS-R (p = 0.020, OR = 2.802), and ALPS-B (p = 0.020, OR = 3.241) all emerged as independent predictors of VNS response.
CONCLUSION: Glymphatic dysfunction is present in DRE and may influence responsiveness to VNS. Higher ALPS indices predicted better treatment outcomes, supporting ALPS potential as a noninvasive imaging biomarker for presurgical stratification in epilepsy.