# Glymphatic system dysfunction in temporal lobe epilepsy with hippocampal sclerosis: MRI-based evaluation of circulatory markers and disease progression

**Authors:** Yingpeng Kuang, Dingwen Hu, Hui Chu, Rongyu Zhang, Ziyu Diao, Kun Wang, Xiaomei Yue, Yuna Chen, Shijun Qiu, Jie An

PMC · DOI: 10.3389/fnins.2026.1741257 · Frontiers in Neuroscience · 2026-02-19

## TL;DR

This study uses MRI to show that the glymphatic system is impaired in people with temporal lobe epilepsy and hippocampal sclerosis, with changes linked to disease duration.

## Contribution

The study introduces MRI-based glymphatic markers as potential imaging biomarkers for disease progression in TLE-HS.

## Key findings

- TLE-HS patients showed reduced DTI-ALPS and CPV/TIV compared to healthy controls.
- Longer disease duration was associated with lower DTI-ALPS and higher FW-WM.
- Reduced hippocampal volume correlated with decreased DTI-ALPS and increased CPV.

## Abstract

In this study, several MRI-derived glymphatic markers were utilized to evaluate alterations in glymphatic system (GS) function in patients with temporal lobe epilepsy and hippocampal sclerosis (TLE-HS).

we assessed 160 participants, including 80 patients with TLE-HS and 80 healthy controls (HCs). Glymphatic circulation was evaluated using MRI-based markers, including choroid plexus volume (CPV), perivascular space (PVS) volume, the fraction of white matter free water (FW-WM), and diffusion tensor imaging along the perivascular space (DTI-ALPS) index. Group differences were evaluated using two-sample tests, and associations were assessed using partial Spearman’s rank correlations (ρ).

In patients with TLE-HS, the DTI-ALPS index (t = −2.65, P = 0.001), CPV/TIV (t = −2.65, P = 0.001), and PVS score [χ2,test χ2 (3, N = 160) = 15.21, p = 0.0016] were significantly lower than in HCs, whereas the FW-WM (t = 5.70, P < 0.001) was significantly higher. Additionally, longer disease duration was significantly correlated with a decrease in DTI-ALPS (ρ = −0.375, P = 0.001), an increase in FW-WM (ρ = 0.316, P = 0.001), and an enlargement of CPV (ρ = 0.378, P = 0.001). Furthermore, a reduction in hippocampal volume (HPV) was closely correlative with a decrease in DTI-ALPS (ρ = 0.226, P = 0.048) and an enlargement of CPV (ρ = −0.345, P = 0.002).

This study offers substantiated evidence of GS function in patients with TLE-HS using multiple MRI-derived indices of GS function. Moreover, longer disease duration was significantly associated with lower DTI-ALPS indices, higher FW-WM levels, and enlarged CPV, while reduced HPV was closely linked to decreased DTI-ALPS and increased CPV. These findings indicate that MRI-derived GS indices may serve as potential imaging biomarkers of disease chronicity in TLE-HS.

## Linked entities

- **Diseases:** temporal lobe epilepsy (MONDO:0005115)

## Full-text entities

- **Genes:** APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, AQP4 (aquaporin 4) [NCBI Gene 361] {aka MIWC, MLC4, WCH4, hAQP4}
- **Diseases:** head trauma (MESH:D006259), volume loss (MESH:D016388), neurodegenerative (MESH:D019636), inflammation (MESH:D007249), edema (MESH:D004487), neuroinflammation (MESH:D000090862), intracranial lesions (MESH:D020765), hippocampal atrophy (MESH:D001284), HS (MESH:C567159), ALPS (MESH:D056735), TLE-HS (MESH:D004833), tumors (MESH:D009369), psychiatric disorders (MESH:D001523), neurotoxic (MESH:D020258), structural injury (MESH:D020914), structural abnormalities (MESH:C566527), focal epilepsy (MESH:D004828), cerebral edema (MESH:D001929), sclerosis (MESH:D012598), SLE (MESH:D008180), neurological disorders (MESH:D009461), Seizure (MESH:D012640), small vessel disease (MESH:D059345), Encephalopathy (MESH:D001927), demyelination (MESH:D003711), Epilepsy (MESH:D004827), gliosis (MESH:D005911), HPV (MESH:D000092223), CP (MESH:D020288), circulation (MESH:D009360), GS (MESH:D015619), PVS (MESH:D054973), chronic epilepsy (MESH:D002908), iRBD (MESH:D020187), cognitive impairment (MESH:D003072), epilepsy-related disorders (MESH:D019973), multiple sclerosis (MESH:D009103)
- **Chemicals:** water (MESH:D014867), antiepileptic medications (-), glucose (MESH:D005947)
- **Species:** Homo sapiens (human, species) [taxon 9606], Rodentia (rodent, order) [taxon 9989]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12960557/full.md

## References

60 references — full list in the complete paper: https://tomesphere.com/paper/PMC12960557/full.md

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Source: https://tomesphere.com/paper/PMC12960557