Authors :
Presenting Author: Priyanka Venkata Sita Illapani, MSc – Children's National Hospital
Lauren Reppert, BS – Texas Children's
Joelle Sarlls, PhD – NIH
William Theodore, MD – National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland, USA
William Gaillard, MD – Children's National Hospital
Madison Berl, PhD – Children's National Hospital
Sara Inati, PhD – National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland, USA
Leigh Sepeta, PhD – Children's National Hospital
Rationale:
The glymphatic system which involves cerebrospinal fluid (CSF), interstitial fluid (ISF), and glial cells, is responsible for removing metabolic waste and maintaining neural health. Diffusion Tensor Imaging–Analysis along the Perivascular Space (DTI-ALPS) is a non-invasive method to assess glymphatic function by measuring fluid diffusivity along perivascular spaces (Taoka et al., 2017). Glymphatic dysfunction has been linked to neuroinflammation, tissue degeneration, and cognitive decline (Corbali et al., 2025). In temporal lobe epilepsy (TLE), prior studies have shown reduced ALPS index correlates with poorer cognitive performance, implicating glymphatic impairment in disease progression (Zhang et al., 2023). Additionally, lateralized glymphatic dysfunction—more pronounced on the side of seizure focus—has been observed in TLE patients. These findings suggest that DTI-ALPS may serve as a sensitive imaging biomarker for neuroinflammatory burden, structural asymmetry, and potential cognitive vulnerability in TLE (Zhao et al., 2023). We aim to use DTI-ALPS to investigate the dysfunction and hemispheric differences in glymphatic system for patients with TLE. We hypothesize that the dysfunction will be reduced ipsilateral to the seizure focus.
Methods:
21 adults with TLE were included from a larger multi scanner NIH study (Mean age (SD) = 35.2(11.9)); nine had left TLE. Data was also acquired from 12 healthy controls for comparison. Participants were scanned in Siemens (3T) scanner to obtain 45 direction multi b shell (3 B0, b-value - 200,500 and 1100) diffusion weighted images and a T1-weighted image. FSL software was used to correct for eddy current induced distortions and movement artifact. A diffusion tensor model was fit voxel-wise to derive fractional anisotropy (FA) and directional diffusivity (x-, y-, z-axis) maps. A combination of linear and non-linear registration techniques was employed to register diffusion images to standard space (MNI152 1mm template). 5mm diameter defined sphere’s on superior corona radiata (SCR) and the superior longitudinal fasciculus (SLF) based on the JHU-ICBM-DTI-81-white-matter were used in native space to calculate bilateral ALPS indexes (Liu et al., 2023). R-studio was used to perform statistical analysis.
Results:
Analysis of variance (ANOVA) revealed a trend-level group effect in left ALPS index across controls, left TLE, and right TLE patients (F(2,31) = 2.66, p = 0.086). Post-hoc Tukey comparisons indicated a trend-level reduction in left ALPS in left TLE compared to controls (p = 0.074), with no significant differences between right TLE and other groups. Right ALPS index did not show any significant group differences.
Conclusions:
These findings suggest a possible lateralized glymphatic disruption in left TLE, particularly affecting the ipsilateral hemisphere, consistent with prior work showing impaired perivascular clearance in focal epilepsy. However, larger samples are needed to confirm these effects, we plan to add more patients with focal epilepsy and healthy controls.
Funding: K23 Award - 5K23NS093152-04