Authors :
Tianyu Song, MD – Beijing Children's Hospital
Presenting Author: Jie Deng, MD – Beijing Children's Hostipal
Chunhong Chen, MD – Beijing Children's Hospital
Xiaohui Wang, MD – Beijing Children's Hospital
Tongli Han, MD – Beijing Children's Hospital
Xu Wang, MD – Beijing Children's Hospital
Xiaojuan Tian, MD – Beijing Children's Hospital, Capital Medical University, National Center for Children's Health
Hongwei Zhang, MD – Jinan Children's Hospital
Yanli Ma, MD – Henan Children's Hospital
Yushanjiang Niyazi, MD – Xinjiang Children's Hospital
Fang Fang, MD – Beijing Children's Hospital, Capital Medical University
Rationale: To evaluate the effectiveness and tolerability of ketogenic diet therapy (KDT) in infants with genetic developmental epileptic encephalopathy (DEE).
Methods:
We reviewed data from patients with DEE due to a single gene variant and onset within 2 years of age who underwent KDT at Beijing Children's Hospital, Jinan Children's Hospital, Henan Children's Hospital, and Xinjiang Children's Hospital between January 2016 and December 2021. Their prognosis was followed up for at least 2 years, and the efficacy, safety, and influencing factors were statistically analyzed.
Results:
A total of 90 patients were included. Thirty pathogenetic genes were identified, with ion channels being the most common (54.4%). The phenotype was dominated by infantile epileptic spasm syndrome (31.1%) followed by Dravet syndrome (23.3%). The age of onset of epilepsy was 2.0 (0.65, 5.25) months. The age of initiation of KDT was 11.0 (5.75, 21.75) months and the time interval to seizure onset was 8.0 (4.0, 18.25) months. KDT was maintained for 10.0 (5.0, 19.0) months. The peak lipid-nonlipid ratio was (2.414±0.739): 1, and blood β-hydroxybutyrate was 2.541±0.697 mmol/L.
The overall efficacy (≥50% reduction in seizure frequency) of KDT was 70.0%, with 34.5% of patients achieved seizure freedom for at least 6 months. Patients with the
STXBP1 variant had the highest seizure control rate of 80% (4/5); individual differences in efficacy were seen for
CDKL5,
KCNQ2,
KCNT1,
SCN1A and
SCN2A, with seizure control rates of 44.5% (4/9), 33.3% (2/6), 20.0% (1/5), 29.2% (7/24) and 22.2% (2/9), respectively. Genotype and maximum lipid-nonlipid ratio are factors influencing seizure freedom, with patients with ion channel gene variants having lower seizure freedom than the other gene variants; no significant difference in keto levels between patients with different lipid-nonlipid ratios, those with lower ratios having a higher seizure-free rate. Females, short interval between seizure onset and KDT, and patients diagnosed with infantile epileptic spasm syndrome and early infantile DEE also responded better to KDT.
Overall, 65.6% patients experienced adverse reactions during KDT. The most common were gastrointestinal reactions (58.9%) which were usually mild and reversible, followed by mild dyslipidemia (8.9%). The most common reason for discontinuing KDT was dissatisfaction with efficacy (39.9%), followed by adverse reactions (19.2%), and increasing the lipid-nonlipid ratio in a short term is more likely to lead to intolerance and discontinuation.
Conclusions:
In this study, KDT was effective in 70.0% of patients with infantile onset genetic DEE, and nearly half of them achieved seizure freedom. Patients with non-ion channel gene variants were more likely to achieve seizure freedom; patients with
STXBP1 variant have the best effectiveness,
CDKL5,
KCNQ2,
SCN1A and
SCN2A also worth trying KDT, earlier initiation of KDT may be more beneficial. KDT was well tolerated in most young patients, with gastrointestinal adverse reactions being the most common. To ensure the tolerance, it is recommended that the lipid-nonlipid rate is not increased too quickly, and there's no need to aim for a high ratio.
Funding: N/A