# Glymphatic dysfunction as a predictor of response to lacosamide add-on therapy in drug-resistant focal epilepsy

## TL;DR

This study shows that a brain imaging measure called DTI-ALPS can predict if patients with drug-resistant epilepsy will respond to lacosamide treatment.

## Contribution

The study introduces DTI-ALPS as a novel noninvasive biomarker for predicting treatment response in drug-resistant focal epilepsy.

## Key findings

- Non-responders to lacosamide had a higher prior medication burden and more epileptiform discharges.
- The DTI-ALPS index was significantly higher in responders compared to non-responders.
- The DTI-ALPS index showed moderate predictive value for lacosamide treatment response.

## Abstract

Drug-resistant epilepsy continues to be a major challenge, as treatment response to additional antiseizure medications is often limited, and early prediction remains crucial. The diffusion tensor image analysis along the perivascular space (DTI-ALPS) index has emerged as a noninvasive imaging method to assess glymphatic function, which plays a key role in brain waste clearance. We aimed to evaluate whether the DTI-ALPS index could serve as a valuable prognostic biomarker of treatment response in patients with drug-resistant focal epilepsy receiving lacosamide (LCM) add-on therapy.

We retrospectively enrolled 155 patients with drug-resistant focal epilepsy who underwent diffusion tensor imaging (DTI) prior to initiating LCM add-on therapy and had at least 12 months of clinical follow-up. Patients were classified into LCM responders and non-responders based on seizure reduction. The DTI-ALPS index was calculated from preprocessed DTI data acquired on a 3 T magnetic resonance imaging scanner and compared between the groups.

Among 155 patients with drug-resistant focal epilepsy, 33 were classified into LCM responders and 122 into LCM non-responders. Non-responders had a higher number of prior antiseizure medication (ASM) burden (3 vs. 2, p < 0.001) and more frequent epileptiform discharges on electroencephalography (78.5% vs. 57.6%, p = 0.015). Additionally, the DTI-ALPS index was significantly greater in responders (1.4022 vs. 1.1936, p = 0.024) than in non-responders, and receiver operating characteristic curve analysis showed its predictive value for LCM response (area under the curve = 0.620, p = 0.015).

DTI-ALPS index was significantly lower in non-responders to LCM add-on therapy among patients with drug-resistant focal epilepsy, suggesting that glymphatic dysfunction may contribute to reduced ASM responsiveness and serve as a potential noninvasive biomarker to aid in treatment prediction.