A. Dressler, L. Bonfanti, P. Trimmel-Schwahofer, B. Porsche, S. Bertoli and C. Male (2025). Role of the Ketogenic Diet Therapy and ACTH as Second Treatments in Drug-Resistant Infantile Epileptic Spasms Syndrome. Nutrients, 17(13). https://doi.org/10.3390/nu17132085

PubMed 40647190

[Abstract]
Objectives: The aim of this study was to evaluate the effectiveness of sequential treatments with adrenocorticotropic hormone (ACTH) or ketogenic diet therapy (KDT) in infants with infantile epileptic spasms syndrome (IESS) who did not achieve seizure freedom after initial treatment with either KDT or ACTH. Methods: We conducted a cohort study following a parallel-cohort randomized controlled trial comparing KDT with ACTH as first-line treatment for IESS. Infants who failed to respond were switched per protocol to the alternative treatment (ACTH or KDT) or, if this was not feasible or unsuccessful, to anti-seizure medications (ASMs). The primary outcome was the frequency of sustained seizure freedom at last follow-up. Results: Of 101 infants allocated to the initial treatment phase, N = 67 required further treatment. Of these, 31% (21/67) achieved sustained seizure freedom after the second treatment phase, and 15% (7/46) after rescue treatment with ASMs. KDT as the second treatment achieved sustained seizure freedom in 50% (12/24), compared to 19% (3/16) with ACTH and 9% (2/22) with ASMs. The cumulative response rate after the first and second treatments was 64% for the KDT-ACTH sequence and 68% for the ACTH-KDT sequence. The cumulative response after all three treatment phases was 78% (KDT-ACTH-ASM) and 72% (ACTH-KDT-ASM), respectively. Conclusions: KDT is at least as effective as ACTH as a second treatment and significantly more effective than ASMs in achieving sustained seizure freedom in infants with IESS.