Background Drug resistant epilepsy (DRE) in children is a common neurological disorder during childhood. Approximately one-third of pediatric epilepsy patients fail to achieve sustained seizure freedom despite receiving two appropriate and well-tolerated antiepileptic drugs. Long-term, recurrent seizures or status epilepticus can severely impact a child's cognition, memory, quality of life, psychosocial development, and physical growth. Additionally, DRE causes multifaceted irreversible damage to a child's neurological development.
Objective To explore risk factors contributing to DRE in children and its impact on the development of different functional regions in pediatric patients.
Methods This study enrolled 250 newly diagnosed pediatric epilepsy patients from the Department of Pediatric Neurology at the Third Affiliated Hospital of Zhengzhou University between January 2023 and October 2024. Based on drug treatment efficacy, they were categorized into a drug-resistant group (n=94) and a non-drug-resistant group (n=156). A control group of 80 typically developing children who underwent the Chinese version of the Griffiths Mental Development Scale (GDS-C) assessment at the same hospital during the same period served as the normal control group. We collected clinical data and GDS-C assessment results for pediatric patients, evaluating six domains: motor, personal and social, language, eye-hand coordination, performance, and practical reasoning. Statistical analysis was performed using SPSS 25.0 software. Multivariate Logistic stepwise regression analysis was employed to explore risk factors for DRE in children. The ROC curve for predicting childhood DRE was plotted using high-risk factors and composite indicators.
Results The drug-resistant group and non-drug-resistant group differed significantly in body weight, age at onset, initial trigger for first seizure, seizure pattern changes, genetic etiology, structural etiology, unknown etiology, pre-treatment seizure duration, pre-treatment seizure frequency, status epilepticus, efficacy of first antiepileptic drug, developmental delay, history of febrile seizures, birth history, fibrinogen, blood ammonia, ceruloplasmin, vitamin D, cranial MRI, initial EEG, EEG after 6 months of treatment, multifocal epileptiform discharges, chromosomal and genetic testing. Differences were statistically significant (P<0.05). Results of the multivariate Logistic stepwise regression analysis revealed that poor efficacy of the first antiepileptic drug (OR=18.928, 95%CI=8.392-42.693, P<0.001), prolonged seizure duration prior to treatment (OR=1.089, 95%CI=1.006-1.180, P=0.036), developmental delay (OR=3.415, 95%CI=1.504-7.754, P=0.003), and and multifocal epileptiform discharges (OR=5.265, 95%CI=2.335-11.873, P<0.001) were identified as high-risk factors for DRE in children. ROC curve analysis revealed that the combined indicators achieved an area under the curve (AUC) of 0.920 (95%CI=0.887-0.953) for predicting childhood DRE, with an optimal cutoff value of 0.316, sensitivity of 0.904, and specificity of 0.801. Comparisons of developmental quotients across six functional domains among children in the control group, refractory group, and non-refractory group revealed statistically significant differences (P<0.05). Specifically, children in the non-refractory group demonstrated higher developmental quotients in motor skills, personal and social skills, language, and hand-eye coordination than those in the refractory group, but lower than those in the control group (P<0.05).
Conclusion Poor response to initial antiepileptic drugs, prolonged seizure duration prior to treatment, developmental delay, and multifocal epileptiform discharges are high risk factors for childhood DRE. The constructed combined indicator prediction model holds clinical reference value; children with DRE exhibit significant developmental lag across multiple functional regions.
