Efficacy and tolerability of the ketogenic diet versus high‐dose adrenocorticotropic hormone for infantile spasms: A single‐center parallel‐cohort randomized controlled trial

Abstract

Summary Objective To compare the efficacy and safety of the ketogenic diet (KD) with standard adrenocorticotropic hormone (ACTH) treatment in infants with West syndrome. Methods In this parallel‐cohort (PC) randomized controlled trial (RCT), infants were randomly allocated to KD or high‐dose ACTH. Those who could not be randomized were followed in a PC. Primary end point was electroclinical remission at day 28. Secondary end points were time to electroclinical remission, relapse after initial response, seizure freedom at last follow‐up, adverse effects, and developmental progress. Results One hundred one infants were included: 32 in the RCT (16 KD; 16 ACTH) and 69 in the PC (37 KD; 32 ACTH). Electroclinical remission at day 28 was similar between KD and ACTH (RCT: 62% vs 69%; PC: 41% vs 38%; combined cohort: 47% vs 48%; KD vs ACTH, respectively). In the combined cohort, time to electroclinical remission was similar between both treatments (14 days for KD, 16 days for ACTH). However, relapse rates were 16% (KD) and 43% (ACTH, P = 0.09), and seizure freedom at last follow‐up was 40% (KD) and 27% (ACTH, P = 0.18). Adverse effects needing acute medical intervention occurred more often with ACTH (30% with KD, 94% with ACTH, P < 0.001). Age‐appropriate psychomotor development and adaptive behavior were similar. Without prior vigabatrin (VGB) treatment, remission at day 28 was 47% (KD) and 80% (ACTH, P = 0.02); relapse rates were 29% (KD) and 56% (ACTH, P = 0.13). Consequently, seizure freedom at last follow‐up was similar. In infants with prior VGB, seizure freedom at last follow‐up was 48% (KD) and 21% (ACTH, P = 0.05). Significance The study is underpowered; therefore, its results should be interpreted with caution. KD is as effective as ACTH in the long term but is better tolerated. Without prior VGB treatment, ACTH remains the first choice to achieve short‐term remission. However, with prior VGB, KD was at least as effective as ACTH in the short term and was associated with lower relapse rates in the long term; therefore, it represents an appropriate second‐line treatment after VGB.

Ketogenic Dietary Therapy Controversies for Its Second Century

“…10 Some of these conditions do have limited published evidence for early or first-line ketogenic dietary therapy use, primarily for infantile spasms, epilepsy with myoclonic-atonic seizures (Doose syndrome), and glucose transporter type 1 (Glut1) deficiency syndrome. [13][14][15] Genetic testing, especially for SLC2A1 mutations for Glut1 deficiency, may in the future identify patients responsive to ketogenic dietary therapy earlier than ever before, perhaps even before seizures begin.…”

Is adrenocorticotropic hormone (ACTH) therapy loaded with severe side effects? Do not use synthetic ACTH at the same dosages as “natural” ACTH

“…To the Editors: I read with great interest the recent paper by Dressler et al on the efficacy and tolerability of the ketogenic diet versus high-dose adrenocorticotropic hormone (ACTH) for infantile spasms. 1 The conclusions are the following: "KD [ketogenic diet] is as effective as ACTH in the long term but is better tolerated. Adverse effects needing acute medical intervention occurred more often with ACTH (30% with KD, 94% with ACTH, respectively; P < .001)."…”

Response to “Is ACTH therapy loaded with severe side‐effects? Do not use synthetic ACTH with the same dosages as ‘natural’ ACTH”

“…To the Editor-in-Chief of Epilepsia We thank Professor Riikonen for her interest in our study 1 and appreciate the opportunity to respond to her remarks:…”