Objectives Peak width of skeletonized mean diffusivity (PSMD) is a neuroimaging biomarker of white matter integrity in cerebral small-vessel disease. However, the significance of PSMD in focal epilepsy remains unclear. This study aimed to investigate alterations in white matter microstructure and glymphatic system function in patients with focal epilepsy by comparing PSMD and the diffusion tensor imaging (DTI) along perivascular spaces (DTI-ALPS) index with healthy controls and by exploring their associations with seizure lateralization and treatment response. Methods We retrospectively analyzed DTI data from 102 patients with focal epilepsy and 88 healthy controls. PSMD values and the DTI-ALPS index were obtained using a standard processing pipeline, and between-group comparisons were performed. Associations between PSMD and clinical characteristics were also evaluated. Results PSMD was significantly higher in patients with focal epilepsy than in healthy controls (2.218 ± 0.355 × 10−4 vs. 2.051 ± 0.176 × 10−4 mm2/s, p < 0.001). In addition, PSMD was significantly higher in the ipsilateral hemisphere than in the contralateral hemisphere (2.239 ± 0.356 × 10−4 vs. 2.109 ± 0.325 × 10−4 mm2/s, p = 0.005). The DTI-ALPS index was significantly lower in patients with focal epilepsy than in healthy controls (1.628 ± 0.256 vs. 1.718 ± 0.305, p = 0.028). PSMD was positively correlated with age in patients (r = 0.417, p < 0.001) and controls (r = 0.343, p = 0.001) and negatively correlated with the DTI-ALPS index in patients (r=-0.376, p < 0.001) and controls (r=-0.409, p < 0.001). Conclusion Our findings suggest that PSMD is increased in patients with focal epilepsy, potentially reflecting microstructural white matter alterations. Increased PSMD in the ipsilateral hemisphere supports its potential role in lateralizing seizure onset. The significant positive correlation between PSMD and age and the inverse relationship between PSMD and the DTI-ALPS index suggest that PSMD is associated with changes in the glymphatic system and white matter microstructure.

White matter and glymphatic system alterations in patients with focal epilepsy: insights from PSMD and DTI-ALPS index

期刊论文
发表日期：

2025年9月30日

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Ho-Joon Lee,
Dong Ah Lee,
Kang Min Park

摘要

Objectives

Peak width of skeletonized mean diffusivity (PSMD) is a neuroimaging biomarker of white matter integrity in cerebral small-vessel disease. However, the significance of PSMD in focal epilepsy remains unclear. This study aimed to investigate alterations in white matter microstructure and glymphatic system function in patients with focal epilepsy by comparing PSMD and the diffusion tensor imaging (DTI) along perivascular spaces (DTI-ALPS) index with healthy controls and by exploring their associations with seizure lateralization and treatment response.

Methods

We retrospectively analyzed DTI data from 102 patients with focal epilepsy and 88 healthy controls. PSMD values and the DTI-ALPS index were obtained using a standard processing pipeline, and between-group comparisons were performed. Associations between PSMD and clinical characteristics were also evaluated.

Results

PSMD was significantly higher in patients with focal epilepsy than in healthy controls (2.218 ± 0.355 × 10⁻⁴ vs. 2.051 ± 0.176 × 10⁻⁴ mm²/s, p < 0.001). In addition, PSMD was significantly higher in the ipsilateral hemisphere than in the contralateral hemisphere (2.239 ± 0.356 × 10⁻⁴ vs. 2.109 ± 0.325 × 10⁻⁴ mm²/s, p = 0.005). The DTI-ALPS index was significantly lower in patients with focal epilepsy than in healthy controls (1.628 ± 0.256 vs. 1.718 ± 0.305, p = 0.028). PSMD was positively correlated with age in patients (r = 0.417, p < 0.001) and controls (r = 0.343, p = 0.001) and negatively correlated with the DTI-ALPS index in patients (r=-0.376, p < 0.001) and controls (r=-0.409, p < 0.001).

Conclusion

Our findings suggest that PSMD is increased in patients with focal epilepsy, potentially reflecting microstructural white matter alterations. Increased PSMD in the ipsilateral hemisphere supports its potential role in lateralizing seizure onset. The significant positive correlation between PSMD and age and the inverse relationship between PSMD and the DTI-ALPS index suggest that PSMD is associated with changes in the glymphatic system and white matter microstructure.