Background

Infantile spasms (West syndrome) is a clinically common epilepsy syndrome of multiple causes, with typical manifestations of spasms, hypsarrhthmia (typical finding on interictal electroencephalogram [EEG]), and psychomotor development delay [1]. Although corticotropin (ACTH) and vigabatrin are used as the first-line treatment for infantile spasms, the epileptic spasms of some patients could not be effectively controlled. In addition, although ACTH is recommended as the first-line treatment in many countries, it has a high incidence of side effects and infantile spasms may relapse in nearly 33–50% of patients, which limits its generalized use [2,3,4]. Ketogenic diet (KD), a dietary model with high fat, low carbohydrate, and appropriate protein and other nutrients, can not only control seizures, but also improve EEG, development and cognition, thus having become an effective non-drug treatment for drug-resistant infantile spasms [5,6,7]. KD has developed rapidly since its introduction in China in 2004 [14, 16, 22,23,24]. Based on this report involving 17 epilepsy centers, although there was no overall difference in the efficiency and retention rate among centers (P > 0.05), in reality, the concept of KD management, the degree of family cooperation and the freedom of patients’ choice of medical treatment can all affect the retention rate. The retention rate further decreased from 3 months of KD, which may be related to the fact that the effect of KD was usually evaluated at 3–6 months. It is often more difficult to adhere to KD when the patient’s family believe that it is ineffective or the effect does not meet the expectation. In the withdrawal analysis, 20.0% of withdrawal were due to poor seizure improvement, which was similar to the previously reported results [6]; 17.1% of patients stopped KD due to family loss of follow-up and poor compliance / poor parental cooperation, which may be related to the difficulty in understanding KD by the elderly of some families or the difficulty of young parents in KD implementation. At the same time, 4.1% of patients received add-on of new ASMs or hospital transferring treatment, which not only reflected the flexibility of medical care, but also indicated that the effect of short-term KD might not meet the expectations of their families. Therefore, how to improve the effectiveness of KD individually, do a good job in the whole process of management, make evaluation of KD quantifiable, and simplify the operation are key issues that should receive more attention and be solved at present, because the KD retention rate is an important prognostic factor for maintenance of the curative effect [6].

In our study, adverse events occurred in some patients, but most of them were transient and tolerable, which were improved by conservative treatment or dietary adjustment. The incidence of hypoproteinemia, kidney stones, high triglycerides or cholesterol was low, and throughout the KD period, the incidence of adverse events was also low (< 2.0%). Good diet management and a reasonable scheme can reduce the occurrence of adverse events and increase the safety. Seizure control effect, expectation and dietary compliance play a key role in the continuation of KD. During KD, 8 patients died from different causes. Although the deaths were not directly caused by KD, careful observation is still needed during diet therapy to reduce complications and ensure a timely and appropriate treatment at its occurrence.

As a multicenter retrospective multicenter cohort study, the data might not be completely accurate. The long-term retention rate and the effectiveness rate, although similar to those reported in a prospective controlled study, were low in this study. In the future, multi-center large-sample clinical trials should be designed to study the related factors of retention rate and effectiveness, and further improve them.

Conclusions

In this study, we analyzed the effect and safety of KD treatment in 481 patients with infantile spasms from multicenter registered trial between 2014 to 2020. Most of the patients had drug-resistant epilepsy. At 1, 3, 6 and 12 months of KD, the seizure freedom rates were 6.9%, 11.6%, 16.0% and 16.8% respectively, and the retention rates were 94.0%, 82.5%, 55.7% and 33.1%, correspondingly. In summary, KD is effective in the treatment of infantile spasms with mild and acceptable side effects, and thus is suitable for clinical application. The anti-seizure effect and cognition improvement of KD therapy need to be further studied.