Ketogenic Diet Therapy for Drug-Resistant Epilepsy and Cognitive Impairment in Children With Tuberous Sclerosis Complex

Abstract

ObjectiveTuberous sclerosis complex (TSC) is a rare disease with a high risk of epilepsy and cognitive impairment in children. Ketogenic diet (KD) therapy has been consistently reported to be beneficial to TSC patients. In this study, we aimed to investigate the efficacy and safety of KD in the treatment of drug-resistant epilepsy and cognitive impairment in children with TSC.MethodsIn this multicenter study, 53 children (33 males and 20 females) with drug-resistant epilepsy or cognitive impairment caused by TSC were retrospectively recruited from 10 hospitals from January 1, 2010, to December 31, 2020. Intention-to-treat analysis was used to evaluate seizure reduction and cognition improvement as outcomes after KD therapy.ResultsOf the 53 TSC patients included, 51 failed to be seizure-free with an average of 5.0 (range, 4–6) different anti-seizure medications (ASMs), before KD therapy. Although the other two patients achieved seizure freedom before KD, they still showed psychomotor development delay and electroencephalogram (EEG) abnormalities. At 1, 3, 6, and 12 months after the KD therapy, 51 (100%), 46 (90.2%), 35 (68.6%), and 16 patients (31.4%) remained on the diet therapy, respectively. At these time points, there were 26 (51.0%), 24 (47.1%), 22 (43.1%) and 13 patients (25.5%) having ≥50% reductions in seizure, including 11 (21.6%), 12 (23.5%), 9 (17.6%) and 3 patients (5.9%) achieving seizure freedom. In addition, of 51 patients with psychomotor retardation, 36 (36 of 51, 70.6%) showed cognitive and behavioral improvements. During the KD therapy, no serious side effects occurred in any patient. The most common side effects were gastrointestinal disturbance (20 of 53, 37.7%) and hyperlipidemia (6 of 53, 11.3%). The side effects were gradually relieved after adjustment of the ketogenic ratio and symptomatic treatment.ConclusionKD is an effective and safe treatment for TSC-related drug-resistant epilepsy and cognitive impairment in children. KD can reduce seizure frequency and may potentially improve cognition and behavior.

A single-center observational study on long-term neurodevelopmental outcomes in children with tuberous sclerosis complex

“…Furthermore, VNS is established and recommended for the treatment of drug resistant TSC-associated epilepsy [45,46]; however, randomized-controlled trials are missing. Ketogenic diets, which effectively reduced seizure frequency in a small and heterogenous study group of patients with TSC [47,48], were not applied in our patients, which was comparable to other studies in which this treatment option was rare in TSC patients [30,38]. One explanation could be that randomized-controlled studies on these therapeutic options are still lacking.…”

The use of ketogenic diets in children living with drug‐resistant epilepsy, glucose transporter 1 deficiency syndrome and pyruvate dehydrogenase deficiency: A scoping review

“…The most common research type was retrospective cohort study (39.4%, n = 126), 69–194 followed by prospective cohort study (21.9%, n = 70) 195–264 . The remaining quantitative study designs included case series (10.7%, n = 34),…”

Dietary carbohydrates in the management of epilepsy

“…However, this raises the possibility of miscellaneous factors that may have made the 4 : 1 diet more tolerable to these patients, such as the presence of a G-tube [12]. Other studies did not find a significant difference in the efficacy of the ketogenic diet in groups with differing ketogenic ratios [13]. Increasing the ratio of the diet was associated with less compliance in adolescents and adults, though the latter reported an improvement in general health score questionnaires [14].…”