Neurodevelopmental Risk Factors and Comparative Efficacy of Ketogenic Diet in Children With Spike-Wave Activation in Sleep: A Cohort Study.

BACKGROUND

Children with spike-wave activation in sleep (SWAS) face significant neurodevelopmental impairments, including cognitive deficits, oropharyngeal dysfunction and attention-deficit/hyperactivity disorder (ADHD). While SWAS is a known contributor, the impact of specific clinical factors and the comparative efficacy of treatments like ketogenic diet (KD), steroids, and benzodiazepines (BZDs) on outcomes remain unclear.

METHODS

This retrospective cohort study analyzed 134 children with SWAS treated at Children's Hospital of Chongqing Medical University (2015-2024). Clinical data, electroencephalograph, neurodevelopmental assessment, and treatment response were collected.

RESULTS

Treatment included KD (n = 11), steroids (n = 72), BZDs (n = 105, including a high-dose diazepam subgroup n = 5), and antiseizure medication (ASM) adjustments (n = 275). Higher seizure frequency correlated significantly with increased cognitive impairment (P < 0.05), oropharyngeal dysfunction (P < 0.05), ADHD (P < 0.05), and relapse rate (P < 0.05). Earlier seizure onset and SWAS onset predicted higher relapse. Structural abnormalities were associated with earlier seizure onset (P < 0.05) and greater cognitive impairment (P < 0.05). Relapse correlated with earlier onset and higher oropharyngeal dysfunction/ADHD (P < 0.05). Treatment response rates were: KD 81.8% (9/11), steroids 65.3% (47/72), BZDs 47.6% (50/105), ASM adjustments 18.9% (52/275). High-dose diazepam (0.5-1.0 mg/kg/day) achieved 80% (4/5) response. KD, steroids, and BZDs were significantly more effective than ASM adjustments (P < 0.05).

CONCLUSIONS

Seizure frequency is a critical modifiable predictor of neurodevelopmental impairment and relapse in SWAS, independent of SWAS burden. Structural etiology increases cognitive impairment risk. KD demonstrates efficacy for Spike-Wave Index reduction, comparable to steroids and BZDs, with no statistically significant intergroup differences. High-dose diazepam shows promise for refractory cases. ASM adjustments, while less effective for Spike-Wave Index, offer practical seizure control.