Long‐term developmental outcome in infantile epileptic spasms syndrome after high‐dose prednisolone and vigabatrin treatment

OBJECTIVE: To evaluate long-term developmental outcomes and identify independent predictors of favorable developmental outcomes at 3 years of age in children with infantile epileptic spasms syndrome (IESS) treated with a standardized stepwise vigabatrin and high-dose prednisolone protocol. METHODS: This prospective single-center cohort study enrolled 236 children with IESS managed according to a standardized protocol between March 2016 and April 2022 at Severance Children's Hospital. All patients received initial vigabatrin, with high-dose oral prednisolone added for non-vigabatrin responders. Developmental outcome at 3 years was classified as favorable (mental quotient [MQ] ≥ 70 and psychomotor quotient [PMQ] ≥ 70) or unfavorable using the Bayley Scales of Infant and Toddler Development, Second Edition. Independent predictors were identified by multivariable logistic regression using Firth's penalized method to address complete separation. RESULTS: Overall treatment response was achieved in 175 patients (74.2%). At 3 years, 49 patients (20.8%) achieved favorable developmental outcome. On multivariable analysis, etiology and treatment response were the only independent predictors. Compared to unknown etiology, structural etiology (aOR 0.085; 95% CI 0.026-0.281; p < 0.001) and genetic etiology (aOR 0.023; 95% CI 0.002-0.357; p = 0.007) were associated with significantly lower odds of favorable developmental outcome. Unresponsive patients had markedly lower odds compared to vigabatrin responders (aOR 0.030; 95% CI 0.002-0.523; p = 0.02). Notably, none of the 49 patients with genetic etiology and none of the 61 unresponsive patients achieved favorable developmental outcome. Lead time showed a significant univariable association, but this association was attenuated after adjustment for other prognostic factors. SIGNIFICANCE: Etiology and treatment response are the dominant independent predictors of favorable developmental outcome at 3 years in children with IESS. These findings underscore the need for early etiological diagnosis and individualized treatment strategies, particularly in patients with genetic etiology or those unresponsive to first-line therapy. PLAIN LANGUAGE SUMMARY: Infantile epileptic spasms syndrome (IESS) is a severe epilepsy of infancy that often leads to lasting developmental problems. In this study of 236 children with IESS treated with a stepwise vigabatrin and prednisolone protocol, developmental outcome at age 3 was mainly associated with the underlying cause of IESS and response to treatment. Children without an identified underlying cause and those who responded to treatment had better developmental outcomes than children with a structural or genetic cause or those who did not respond. These findings emphasize the importance of careful evaluation and individualized treatment in children with IESS.