Department of Pediatrics and Adolescent Health, Medical University of Vienna, Vienna, Austria.
Department of Child and Adolescent Psychiatry, Medical University of Vienna, Vienna, Austria.
Epilepsia. 2019 Mar;60(3):441-451. doi: 10.1111/epi.14679. Epub 2019 Feb 23.
To compare the efficacy and safety of the ketogenic diet (KD) with standard adrenocorticotropic hormone (ACTH) treatment in infants with West syndrome.
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.
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).
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.
比较生酮饮食（KD）与标准促肾上腺皮质激素（ACTH）治疗婴儿 West 综合征的疗效和安全性。
在这项平行队列（PC）随机对照试验（RCT）中，将婴儿随机分配至 KD 或高剂量 ACTH 治疗组。不能进行随机分组的婴儿则进行 PC 随访。主要终点为 28 天的临床电缓解。次要终点为临床电缓解时间、初始反应后的复发、末次随访时的无癫痫发作、不良反应和发育进展。
共纳入 101 例婴儿：32 例纳入 RCT（KD 16 例，ACTH 16 例），69 例纳入 PC（KD 37 例，ACTH 32 例）。28 天的临床电缓解在 KD 和 ACTH 之间相似（RCT：62% vs 69%；PC：41% vs 38%；联合队列：47% vs 48%；KD 与 ACTH 分别比较）。在联合队列中，两种治疗的临床电缓解时间相似（KD 14 天，ACTH 16 天）。然而，复发率分别为 16%（KD）和 43%（ACTH，P = 0.09），末次随访时的无癫痫发作率分别为 40%（KD）和 27%（ACTH，P = 0.18）。需要急性医疗干预的不良反应在 ACTH 治疗组更常见（KD 组 30%，ACTH 组 94%，P < 0.001）。适应行为和年龄适当的精神运动发育相似。无先前加巴喷丁（VGB）治疗时，28 天的缓解率分别为 47%（KD）和 80%（ACTH，P = 0.02）；复发率分别为 29%（KD）和 56%（ACTH，P = 0.13）。因此，末次随访时的无癫痫发作率相似。在有先前 VGB 治疗的婴儿中，末次随访时的无癫痫发作率分别为 48%（KD）和 21%（ACTH，P = 0.05）。
该研究的效力不足；因此，其结果应谨慎解读。KD 在长期内与 ACTH 同样有效，但耐受性更好。无先前 VGB 治疗时，ACTH 仍然是实现短期缓解的首选。然而，有先前 VGB 治疗时，KD 在短期内与 ACTH 同样有效，且长期复发率较低；因此，它是 VGB 后的一种合适的二线治疗。
