Neurodevelopmental Risk Factors and Comparative Efficacy of Ketogenic Diet in Children With Spike-Wave Activation in
Jiannan Ma1, Juan Wang1, Xiaojie Song1
1Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, Department of Neurology, Children's Hospital of Chongqing Medical University, Chongqing, China.
Insights
Higher seizure frequency in children with spike-wave activation in sleep (SWAS) predicts neurodevelopmental issues and relapse. Ketogenic diet (KD), steroids, and benzodiazepines (BZDs) show better efficacy than antiseizure medication adjustments.
Area of Science:
- Pediatric Neurology
- Epilepsy Research
- Neurodevelopmental Disorders
Background:
- Children with spike-wave activation in sleep (SWAS) experience significant neurodevelopmental impairments, including cognitive deficits, oropharyngeal dysfunction, and ADHD.
- The specific clinical factors influencing these impairments and the comparative effectiveness of treatments like ketogenic diet (KD), steroids, and benzodiazepines (BZDs) are not well-understood.
Purpose of the Study:
- To investigate the impact of clinical factors on neurodevelopmental outcomes in children with SWAS.
- To compare the efficacy of different treatment modalities (KD, steroids, BZDs, ASM adjustments) for SWAS.
Main Methods:
- Retrospective cohort study of 134 children diagnosed with SWAS.
- Analysis of clinical data, electroencephalography (EEG), neurodevelopmental assessments, and treatment responses.
- Data collected from Children's Hospital of Chongqing Medical University between 2015 and 2024.
Main Results:
- Higher seizure frequency significantly correlated with increased cognitive impairment, oropharyngeal dysfunction, ADHD, and relapse rates (P < 0.05).
- Ketogenic diet (KD) showed an 81.8% response rate, steroids 65.3%, and benzodiazepines (BZDs) 47.6%, significantly outperforming antiseizure medication (ASM) adjustments (18.9%, P < 0.05).
- High-dose diazepam (0.5-1.0 mg/kg/day) achieved an 80% response rate in a subgroup of refractory cases.
Conclusions:
- Seizure frequency is a critical, modifiable predictor of neurodevelopmental impairment and relapse in SWAS, irrespective of SWAS burden.
- Ketogenic diet (KD), steroids, and BZDs are more effective than ASM adjustments for SWAS treatment, with KD showing comparable efficacy to steroids and BZDs.
- High-dose diazepam shows promise for refractory SWAS, while ASM adjustments provide practical seizure control.
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.
