Factors associated with drug-resistant epilepsy in children with epilepsy: a retrospective cohort study

Drug‑resistant epilepsy (DRE) remains a major clinical challenge in children. Understanding clinical factors associated with drug resistance is important for guiding management. We aimed to investigate factors independently associated with DRE in a large cohort of children with epilepsy.

A retrospective cohort study was conducted on children with confirmed epilepsy who received regular follow‑up at two tertiary pediatric epilepsy centers. Patients were classified into DRE [failure of ≥2 adequate anti-seizure medications (ASMs) trials] and non‑DRE groups according to ILAE criteria. Baseline demographic, clinical, electroencephalographic, neuroimaging, and treatment‑related variables were collected. Univariate and multivariate logistic regression analyses were performed to identify factors independently associated with DRE. Treatment‑related variables (number of ASMs tried, maximum concurrent ASMs, and polytherapy at last follow‑up) were excluded from the multivariable model due to their intrinsic relationship with the definition and clinical consequences of DRE. Model discrimination was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC), and calibration was assessed by the Hosmer‑Lemeshow test. The 95% confidence intervals (CIs) for performance metrics were obtained via bootstrap resampling.

A total of 412 children were enrolled, including 100 (24.3%) with DRE. Children with DRE had significantly younger age at onset (4.30±3.40 vs. 6.01±3.50 years, P<0.001), higher baseline seizure frequency, more frequent status epilepticus, neurodevelopmental disorders, and psychiatric comorbidities (all P<0.05). In multivariable analysis excluding treatment‑related variables, generalized seizure type (vs. focal) [adjusted odds ratio (OR) =0.20; 95% CI: 0.04-0.62; P=0.01), history of status epilepticus (adjusted OR =4.86; 95% CI: 2.15-11.13; P<0.001), neurodevelopmental disorder (adjusted OR =3.40; 95% CI: 1.49-7.85; P=0.004), structural etiology (vs. genetic) (adjusted OR =0.25; 95% CI: 0.07-0.92; P=0.040), and older age at onset (adjusted OR =0.91; 95% CI: 0.82-1.00; P=0.046) were independently associated with DRE. The model showed moderate discriminative ability (AUC =0.802; 95% CI: 0.751-0.872).

In this retrospective cohort, seizure type, history of status epilepticus, neurodevelopmental disorder, structural etiology, and older age at onset were independently associated with DRE after excluding treatment‑related variables. These findings suggest that true baseline independently associated variables of DRE are limited, and the diagnosis of DRE itself-failure of two adequate ASM trials-remains the most practical indicator for considering non‑pharmacological therapies. External validation is needed before clinical application.