Objective:The models currently available for predicting the risk of seizure recurrence after antiepileptic drug (AED) withdrawal in adult epilepsy patients include the prediction model developed by Lamberink et al (Lamberink model, 2017) and the Medical Research Council prediction model (MRC model, 1993). However, there was no external validation for the two models. The purpose of this study was to perform an independent external validation and a comparison of the Lamberink model and the MRC model in adult patients. Methods: The study population was recruited from the Wenzhou Epilepsy Follow-up Registry Database (WEFURD). All the predictors of the Lamberink and MRC models and the occurrence of seizure recurrence in the participants were collected based on the WEFURD. Participants' predicted probabilities of seizure recurrence were obtained by a Web-based tool and the prognostic index formula. The external validation of the Lamberink model and the MRC model were quantified by discrimination, calibration, and decision curve analysis (DCA). Results: Of 212 patients, 126 (59.4%) had seizure recurrence after AED withdrawal. The Lamberink 2-year model, the Lamberink 5-year model, the MRC 1-year model, and the MRC 2-year model had areas under the curve of 0.71 (95% confidence interval [CI] = 0.64-0.78), 0.68 (95% CI = 0.60-0.76), 0.60 (95% CI = 0.50-0.69), and 0.58 (95% CI = 0.50-0.66), respectively. Additionally, the Lamberink 2-year model had a significantly better integrated discrimination improvement than the MRC 2-year model (P < .001). Regarding calibration, the Lamberink 2-year model (P = .121) and the MRC 1-year model (P = .264) were well calibrated, but the Lamberink 5-year model (P = .022) and the MRC 2-year model (P = .008) were not. In the DCA, the Lamberink 2-year model performed well at threshold probabilities of 30%-65%. Significance: This external validation shows that the Lamberink 2-year model might be more accurate and has greater clinical benefit than others for guiding drug withdrawal in adult epilepsy clinics. 116 | LIN et aL. K E Y W O R D S adult epilepsy, drug withdrawal, external validation, prediction model, seizure recurrence Key Points • The Lamberink 2-year model had the highest AUC (0.71) among the models in the external validation • The Lamberink 2-year model (P = .121) and the MRC 1-year model (P = .264) were well calibrated, but the other prediction models were not • In the DCA, the Lamberink 2-year model performed well at threshold probabilities of 30%-65%

Background: Epilepsy is a common neurological disease, and neuroinflammation is one of the main contributors to epileptogenesis. Pyroptosis is a type of pro-inflammatory cell death that is related to epilepsy. Agmatine, has anti-inflammatory properties and exerts neuroprotective effects against seizures. Our study investigated the effect of agmatine on the core pyroptosis protein GSDMD in the context of epilepsy.Methods: A chronic epilepsy model and BV2 microglial cellular inflammation model were established by pentylenetetrazole (PTZ)-induced kindling or lipopolysaccharide (LPS) stimulation. H&amp;E and Nissl staining were used to evaluate hippocampal neuronal damage. The expression of pyroptosis and inflammasome factors was examined by western blotting, quantitative real-time PCR, immunofluorescence and enzyme-linked immunosorbent assay (ELISA).Results: Agmatine disrupted the kindling acquisition process, which decreased seizure scores and the incidence of full kindling and blocked hippocampal neuronal damage. In addition, agmatine increased BV2 microglial cell survival in vitro and alleviated seizures in vivo by suppressing the levels of PTZ-induced pyroptosis. Finally, the expression of TLR4, MYD88, phospho-IκBα, phospho-NF-κB and the NLRP3 inflammasome was significantly upregulated in LPS-induced BV2 microglial cells, while agmatine suppressed the expression of these proteins.Conclusions: Our results indicate that agmatine affects epileptogenesis and exerts neuroprotective effects by inhibiting neuroinflammation, GSDMD activation, and pyroptosis. The inhibitory effect of agmatine on pyroptosis was mediated by the suppression of the TLR4/MYD88/NF-κB/NLRP3 inflammasome pathway. Therefore, agmatine may be a potential treatment option for epilepsy.

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Objective: Explore Chinese patients' risk-benefit preferences and willingness-to-pay (WTP) for antiepileptic drugs (AEDs) treatment through the discrete choice experiment (DCE).Method: Six attributes including the efficacy of AEDs, adverse reactions (digestive system, neuropsychic systems, and the effects on the fetus), dosing frequency and drug costs (to estimate patient WTP) were included in the DCE questionnaire based on results collected from literature reviews, expert consultation, and patient survey. The alternative-specific conditional logit model was used to analyze patient preference and WTP for each attribute and its level and to assess the sociodemographic impact and clinical characteristics.Results: A total of 151 valid questionnaires were collected. The result shows that five out of the six attributes are significant, except the dosing frequency. Among the six attributes, the efficacy of AEDs (10.0; 95% CI 8.9–11.1) is mostly concerned by patients, followed by the effects of AEDs on the fetus (8.9; 95% CI 7.7–10.1), duration of side effects in the neuropsychic system (4.9; 95% CI 3.7–6.0) and adverse reactions of the digestive system (3.2; 95% CI 1.5–4.2). The patients surveyed are willing to spend ¥ 1,246 (95% CI, ¥ 632- ¥ 1,861) per month to ensure 100% seizure control, and ¥ 1,112 (95% CI, ¥ 586–¥ 1,658) to reduce the risk of the drug affecting the fetus to 3%. Besides, it was found that personal characteristics including the intention for conception and AEDs treatment regimens have statistical significance.Conclusion: Improving the drug's efficacy and reducing its side effects are predominant considerations for patients with epilepsy in China, especially for those who are concerned about the seizure control and the drug effect on the fetus. This finding is useful to physicians and can encourage shared decision-making between the patients and their doctors in the clinic.