Efficacy of ketogenic diet therapy for pediatric drug-resistant epilepsy with monogenic etiology: A single-arm meta-analysis

CONTEXT: Drug-resistant epilepsy poses very difficult treatment challenges worldwide. Findings regarding the connection between ketogenic diet therapy (KDT) and genetic epilepsy are still unclear. OBJECTIVE: In this meta-analysis we sought to examine the efficacy of KDT for drug-resistant epilepsy in patients with genetic mutations. DATA SOURCES: The data were sourced from studies that reported KDT for epilepsy patients with monogenic etiology and were found in PubMed, Embase, Scopus, Web of Science, Cochrane Library, and 4 Chinese databases from database inception until January 2, 2024. DATA ANALYSIS: We determined that 50 studies involving a total of 849 patients who were treated with KDT met the eligibility criteria for inclusion. The meta-analysis revealed that the responder rate was 58% (95% CI, 49%-67%, I2 = 389%, P < .01) and the seizure-free rate was 29% (95% CI, 19%-39%, I2 = 86%, P < .01). In 40 reported studies, comprising 615 patients, specific gene mutations and response rates after KDT were mentioned. The highest responder rate, which occurred among patients with mutations in the solute carrier family 2 member 1 gene, SLC2A1 (n = 87), was 96% (95% CI, 91%-100%, I2 = 0%, P = .72), and the lowest, which occurred among patients with mutations of the sodium voltage-gated channel alpha subunit 8 gene, SCN8A (n = 5), was 15% (95% CI, 0%-60%, I2 = 39%, P = .20). In 39 studies, including 405 patients, specific gene mutations and seizure-free rates after KDT were reported. The highest seizure-free rate, which occurred in patients with mutations in SLC2A1 (n = 80), was 67% (95% CI, 49%-86%, I2 = 78%, P < .01), and the lowest seizure-free rates occurred in patients with mutations in the cyclin-dependent kinase-like 5 gene, CDKL5, (n = 40) and those with mutations in the potassium sodium-activated channel subfamily T member 1 gene, KCNT1 (n = 48), who had seizure-free rates of 0% (95% CI, 0%-6%, I2 = 0%, P = 1.00) and 2% (95% CI, 0%-7%, I2 = 0%, P = .82), respectively. The maximum efficacy of KDT, reflected by the responder rate (72%) and seizure-free rate (46%), was achieved at the 6-month follow-up, at which patients showed outcomes superior to those demonstrated at earlier or later assessments. CONCLUSIONS: The present meta-analysis revealed the efficacy of KDT in the treatment of genetic epilepsies, particularly in epilepsies associated with SLC2A1 and SCN1A mutations, but KDT had relatively poor efficacy in epilepsies related to CDKL5 and KCNT1 mutations. Notably, compared to other follow-up intervals, at the 6-month post-KDT follow-up interval patients showed the highest overall responder and seizure-free rates. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration No. CRD42024610852.