Altered Along-The-Perivascular Space Index in Functional (Psychogenic Non-Epileptic) Seizures: A Diffusion Tensor Imaging Study of Glymphatic System Function Publisher



M Roozbeh MEHRDAD ; Mm Mirbagheri M MEHDI ; M Arbabi MOHAMMAD ; Aa Asadipooya Ali AKBAR ; F Khodagholi FARIBA ; S Amiri SABA
Source: Epilepsia Open Published:2025

Abstract

Objective: The glymphatic system is a critical brain waste-clearance mechanism that facilitates the removal of metabolic byproducts and maintains neural homeostasis. Its dysfunction has been implicated in various neurological disorders; however, its role in functional (psychogenic nonepileptic) seizures (FS/PNES), a functional neurological condition, remains unexplored. This study aimed to indirectly evaluate glymphatic system function using the along the perivascular space (ALPS) index derived from diffusion tensor imaging (DTI) in patients with FS/PNES compared to healthy controls (HCs). Methods: Twenty-one patients with PNES and 21 HCs underwent DTI scans. Glymphatic system function was assessed using the DTI-ALPS method. The DTI-ALPS index was calculated and analyzed for differences between the groups. Correlations with clinical and cognitive measures, including the Addenbrooke's Cognitive Examination (ACE-III), were investigated. Results: Patients with FS/PNES demonstrated significantly lower DTI-ALPS indices compared to those in HCs in the left hemisphere (1.306 ± 0.171 vs. 1.502 ± 0.224, p = 0.005) and the bilateral hemispheric average (1.262 ± 0.174 vs. 1.415 ± 0.195, p = 0.014). No significant correlations were found between the DTI-ALPS index and clinical, demographic, or cognitive assessments. Significance: This study identified alterations in the DTI-ALPS index in patients with FS/PNES, particularly in the left hemisphere. This finding indirectly suggests disrupted perivascular fluid dynamics in FS/PNES and highlights the need for further research to elucidate the neurobiological underpinnings of FS/PNES with particular attention to the potential role of the glymphatic system in functional neurological disorders. Plain Language Summary: The brain has a cleanup system called the glymphatic system, which removes waste to keep it functioning well. In this study, we examined whether this system works differently in people with functional seizures—seizures not caused by epilepsy. We compared brain scans from individuals with functional seizures and healthy controls. The results showed reduced activity in the glymphatic system, especially on the brain's left side, in those with functional seizures. This suggests that their brains may not clear waste as efficiently. Although this finding may point to brain differences in functional seizures, further research is needed to understand the connection. © 2025 Elsevier B.V., All rights reserved.