Factors influencing efficacy and relapse of adrenocorticotropic hormone in infantile epileptic spasms syndrome

Abstract

Background: Infantile epileptic spasms syndrome (IESS) is a severe epileptic condition characterized by persistent uncontrolled seizures, with some children experiencing recurrent seizures despite multiple pharmacological therapies. The prognostic risk factorsassociated with IESS remain unclear. This study aimed to evaluate the factors influencing the efficacy and relapse of adrenocorticotropic hormone (ACTH) treatment for IESS in infants, as well as to assess the correlation between the Burden of Amplitudes and Epileptiform Discharges (BASED) score and clinical outcomes.

Methods: A retrospective analysis was conducted on a cohort of 88 pediatric patients diagnosed with IESS who received ACTH therapy at our hospital from February 2016 to August 2023. Patients were categorized into response (n = 47) and non-response (n = 41) groups based on their treatment response at day 28. Responders were further classified into relapse and non-relapse groups. A modified Poisson regression model and receiver operating characteristic (ROC) curves were employed to evaluate the positive predictive values.

Results: In this study, a total of 47 patients (53.4 %) responded to ACTH treatment. Patients in the response group demonstrated significantly greater reductions in BASED scores by day 14 of ACTH treatment, yielding an area under the curve (AUC) of 0.859 (95 % CI: 0.782-0.937, P＜0.05), with a sensitivity of 68.1 % and a specificity of 95.1 %. The optimal cut-off point was established at ≥ 2, corresponding to a Youden index of 0.632. Notably, patientswho were on anti-seizure medications (ASMs) before ACTH treatment and those with developmental delay prior to the onset of spasms exhibited lower short-term response rates (P＜0.05), although these factors did not demonstrate predictive value. Among the responders, 20 cases (42.6 %) experienced a relapse, with only those patients showing specific abnormalities on cranial magnetic resonance imaging (MRI) exhibiting a statistically higher proportion of relapse.

Conclusion: Patients receiving ASMs before ACTH treatment and those with developmental delays prior to the onset of spasms may have a less favorable therapeutic response. A reduction in BASED scores of 2 or greater by day 14 of ACTH treatment may signify a potentially positive treatment response. Additionally, patients with IESS who present with specific abnormalities on cranial MRI may have an increased likelihood of relapse following ACTH treatment.

Keywords: Adrenocorticotropic hormone; BASED score; Infantile epileptic spasms syndrome; Prognosis; Relapse.