Neurodevelopmental trajectories and clinical outcomes following ultra‐early epilepsy surgery in infants: A matched cohort study

OBJECTIVE: Surgery is increasingly recognized as an effective treatment for drug-resistant epilepsy in children but remains under-utilized. Evidence on its safety and benefits in infants 6 months or younger is very limited, leaving early surgical decision-making insufficiently supported. METHODS: A matched cohort study included 23 infants with age-dependent epileptic encephalopathy (ADEE) and structural brain abnormalities who underwent epilepsy surgery within 6 months and 115 matched non-surgical controls. Neurodevelopment was assessed using developmental quotient (DQ). Multivariable linear regression and propensity score matching (PSM) were used to examine the association between surgery and neurodevelopmental outcomes, whereas surgical safety and long-term seizure control were also evaluated. RESULTS: Among the 23 surgical infants, the median age at seizure onset was .27 months, and all had congenital brain malformations. Hemimegalencephaly was the most common etiology (n = 13). The mean age at surgery was 3.5 months. Hemispherotomy was the most commonly performed surgical procedure (n = 14). No perioperative death or permanent severe complications were observed. Four (17.4%) infants developed transient unilateral limb weakness and 13.6% had postoperative hydrocephalus. The rate of Engel class Ia was 82.6% at 1 year postoperatively and 78.2% at a mean follow-up of 44.4 months. At last follow-up, 69.6% of the infants had discontinued anti-seizure medications (ASMs). The DQ scores of the control group showed a continuous decline over time, whereas the surgical group showed a more favorable trajectory. Multivariable linear regression analysis revealed that surgery was significantly associated with a higher DQ (β = 30.2, 95% confidence interval CI: 19.5-40.9; p < .001). After 1:1 PSM to control confounding variables, the surgical group had significantly higher DQ scores than the control group in all five neurodevelopmental domains (p < .05). SIGNIFICANCE: Epilepsy surgery performed by an experienced team is safe and feasible for very young infants due to congenital brain malformations, without severe perioperative complications. It provides good long-term seizure control, supports ASM withdrawal, and may protect brain development, potentially stabilizing or even improving neurodevelopment in some infants.