Efficacy and Safety of Dietary Therapies for Childhood Drug-Resistant Epilepsy

Abstract

ImportanceDespite advances in the understanding of dietary therapies in children with drug-resistant epilepsy, no quantitative comparison exists between different dietary interventions.ObjectiveTo evaluate the comparative efficacy and safety of various dietary therapies in childhood drug-resistant epilepsy.Data SourcesSystematic review and network meta-analysis (frequentist) of studies in PubMed, Embase, Cochrane, and Ovid published from inception to April 2022 using the search terms ketogenic diet, medium chain triglyceride diet, modified Atkins diet, low glycemic index therapy, and refractory epilepsy.Study SelectionRandomized clinical trials comparing different dietary therapies (ketogenic diet, modified Atkins diet, and low glycemic index therapy) with each other or care as usual in childhood drug-resistant epilepsy were included. Abstract, title, and full text were screened independently by 2 reviewers.Data Extraction and SynthesisData extraction was conducted following Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. Cochrane risk-of-bias tool was used to assess the study quality. Effect sizes were calculated as odds ratio with 95% CI using random-effects model. The hierarchy of competing interventions was defined using the surface under the cumulative ranking curve.Main Outcomes and MeasuresShort-term (≤3 months) 50% or higher and 90% or higher reduction in seizure frequency and treatment withdrawal due to adverse events were the primary efficacy and safety outcomes.ResultsOf 2158 citations, 12 randomized clinical trials (907 patients) qualified for inclusion. In the short term, all dietary interventions were more efficacious than care as usual for 50% or higher seizure reduction (low glycemic index therapy: odds ratio [OR], 24.7 [95% CI, 5.3-115.4]; modified Atkins diet: OR, 11.3 [95% CI, 5.1-25.1]; ketogenic diet: OR, 8.6 [95% CI, 3.7-20.0]), while ketogenic diet (OR, 6.5 [95% CI, 2.3-18.0]) and modified Atkins diet (OR, 5.1 [95% CI, 2.2-12.0]) were better than care as usual for seizure reduction of 90% or higher. However, adverse event–related discontinuation rates were significantly higher for ketogenic diet (OR, 8.6 [95% CI, 1.8-40.6]) and modified Atkins diet (OR, 6.5 [95% CI, 1.4-31.2]) compared with care as usual. Indirectly, there was no significant difference between dietary therapies in efficacy and safety outcomes.Conclusions and RelevanceThis study found that all dietary therapies are effective in the short term. However, modified Atkins diet had better tolerability, higher probability for 50% or higher seizure reduction, and comparable probability for 90% or higher seizure reduction and may be a sounder option than ketogenic diet. Direct head-to-head comparison studies are needed to confirm these findings.

Landscape of genetic infantile epileptic spasms syndrome—A multicenter cohort of 124 children from India

“…Ketogenic diet, a standard-of-care treatment modality for children with drug-resistant epilepsy was effective in five children and it highlights the need of its trial in resistant cases. 29 The mortality was much less than that reported in IESS, probably due to the lower median age at assessment (18 months). 28,[30][31][32][33][34] Long-term epilepsy outcomes were much better than those reported in previous studies on IESS from India.…”

“…However, response to precision‐based therapy was documented only in children with identified genetic variants in ALDH7A1, PLPBP, PNPO, and SLC2A1 genes. Ketogenic diet, a standard‐of‐care treatment modality for children with drug‐resistant epilepsy was effective in five children and it highlights the need of its trial in resistant cases 29 . The mortality was much less than that reported in IESS, probably due to the lower median age at assessment (18 months) 28,30–34 .…”

Dietary carbohydrates in the management of epilepsy

“…There was no significant difference between the LGIT, MAD, and CKD. However, efficacy outcome was unyielding and lacked good quality robust evidence [22].…”

Gastrointestinal Dysfunction in Genetically Defined Neurodevelopmental Disorders

“…57,58 This is also in striking contrast to the dietary modifications often formulated as comanagement in patients with drug-resistant epilepsy (such as the ketogenic diet or modified Atkins diet). 59 A downside of selective eating is that diets may lack essential nutrients, like zinc. In some studies, the zinc/copper ratio is low in autistic patients, and a twofold higher incidence of zinc deficiency is reported in PMDS versus the general population.…”