Anti-seizure medication response and the glymphatic system in patients with focal epilepsy

Abstract

Background and purpose: We aimed to evaluate (i) glymphatic system function in patients with focal epilepsy in comparison with healthy controls, and (ii) the association between anti-seizure medication (ASM) response and glymphatic system function by using diffusion tensor image analysis along the perivascular space (DTI-ALPS).

Methods: We retrospectively enrolled 100 patients with focal epilepsy who had normal brain magnetic resonance imaging (MRI) findings, and classified them as "poor" or "good" ASM responders according to their seizure control at the time of brain MRI. We also included 79 age- and sex-matched healthy controls. All patients and healthy controls underwent conventional brain MRI and diffusion tensor imaging. The DTI-ALPS index was calculated using the DSI studio program.

Results: Of the 100 patients with focal epilepsy, 38 and 62 were poor and good ASM responders, respectively. The DTI-ALPS index differed significantly between patients with focal epilepsy and healthy controls and was significantly lower in patients with focal epilepsy (1.55 vs. 1.70; p < 0.001). The DTI-ALPS index also differed significantly according to ASM response and was lower in poor ASM responders (1.48 vs. 1.59; p = 0.047). Furthermore, the DTI-ALPS index was negatively correlated with age (r = -0.234, p = 0.019) and duration of epilepsy (r = -0.240, p = 0.016) in patients with focal epilepsy.

Conclusion: Our study is the first to identify, in focal epilepsy patients, a greater reduction in glymphatic system function among poor ASM responders compared to good responders. To confirm our results, further prospective multicenter studies with large sample sizes are needed.

Keywords: anticonvulsants; diffusion tensor imaging; epilepsy; glymphatic system.

FIGURE 1

Process for calculation of the diffusion tensor image analysis along the perivascular space (DTI‐ALPS) index in this study. Dxxproj, diffusivity along the x‐axis in the projection fiber; Dxxassoci, diffusivity along the x‐axis in the association fiber; Dyyproj, diffusivity along the y‐axis in the projection fiber; Dzzassoci, diffusivity along the z‐axis in the association fiber.

FIGURE 2

Differences in the diffusion tensor image analysis along the perivascular space (DTI‐ALPS) index between patients with focal epilepsy and healthy controls and between poor and good anti‐seizure medication (ASM) responders. The DTI‐ALPS index in patients with focal epilepsy was lower than that in healthy controls (a), and the DTI‐ALPS index in poor ASM responders was lower than that in good ASM responders.

FIGURE 3

Correlation analysis between the diffusion tensor image analysis along the perivascular space (DTI‐ALPS index and clinical characteristics in patients with focal epilepsy. The figures indicate significantly negative correlations between the DTI‐ALPS index and age (a), and between the DTI‐ALPS index and the duration of epilepsy (b).