A multicenter retrospective cohort study of ketogenic diet therapy in 481 children with infantile spasms
Authors: Ye Yuanzhen , Sun Dan , Li Hua , Zhong Jianmin , Luo Rong , Li Baomin , Zhu Dengna , Li Dan , Huang Shaoping , Jiang Yuwu , Xiao Nong , Chen Yucai , Zhang Yuqin , Yu Mei , Shen Xiaoyun , Gao Li , Zheng Guo , Zhao Congmin , Yuan Baoqiang , Liao Jianxiang , Qin Jiong ,   CAAE KD group
Published: February 2022

Abstract
Background
Ketogenic diet (KD) therapy is one of the main treatments for drug-resistant epilepsy. However, the KD therapy has been applied in only a small number of infantile spasm cases. In this large multicenter study, we investigated the efficacy of KD therapy in the treatment of infantile spasms.

Methods
In this retrospective, multicenter cohort study, clinical data from main epilepsy centers were analyzed. Patients were classified into different groups according to age, type of drug and whether glucocorticoid was used before initiation of KD.

Results
From October 2014 to March 2020, 481 patients (308 males and 173 females) with infantile spasms were treated with the KD therapy. The age of the patients ranged from 2 months to 20 years, with a mean age of 1 year and 10 months. The number of anti-seizure medications (ASMs) used before KD initiation ranged 0–6, with a median of 3. In different time from initiation(1, 3, 6, and 12 months), the rates of seizure freedom after KD were 6.9, 11.6, 16.0 and 16.8%, respectively (χ2 = 27.1772, P < 0.0001). There was a significant difference in the rate of seizure freedom between 3 months and 1 month (χ2 = 6.5498, P = 0.0105) groups, and 6 months and 3 months (χ2 = 3.8478, P = 0.0498) groups, but not between 12 months and 6 months (χ2 = 0.1212, P = 0.7278) groups. The rates of effectiveness were 44.7, 62.8, 49.1 and 32.0% (χ2 = 93.2674, P < 0.0001), respectively. The retention rates were 94.0, 82.5, 55.7 and 33.1% (χ2 = 483.7551, P < 0.0001), correspondingly. The rate of effectiveness and the retention rate of KD were significantly different among the 1, 3, 6 and 12 months. KD treatment was the first choice in 25 patients (5.2%), 55 patients (11.4%) started KD after the failure of the first ASM, 158 patients (32.8%) started KD after the failure of the second ASM, 157 patients (32.6%) started KD after the failure of the third drug, and 86 patients (17.9%) started KD after the failure of the fourth and more. The KD effect was not related to the number of ASMs used before KD startup (P > 0.05). Two hundred and eighteen patients (45.3%) failed to respond to corticotropin or glucocorticoid before initiation. There was no significant difference in the effectiveness rate at different time points between the group of KD therapy after glucocorticoid failure and the group after non-hormone failure (χ2 = 0.8613, P = 0.8348). The rate of adverse events of KD in 1, 3, 6, and 12 months after KD initiation were 22.3, 21.7, 16.8 and 6.9%, respectively. The adverse events mainly occurred during the first 3 months of KD, and the main adverse events were gastrointestinal disturbance and constipation.

Conclusions
The efficacy of the KD treatment for infantile spasms was not affected by age, medication, and glucocorticoid use before initiation. KD is one of the effective treatments for infantile spasms.

Trial registration
ChiCTR-IIR-16008342. Registered on 22 April, 2016 - Retrospectively registered, https://www.chictr.org.cn.