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What defines response to vagus nerve stimulation in children with drug-resistant epilepsy? A prospective cohort study
Farbod Niazi1,2, Karim Mithani2,3,4, Hrishikesh Suresh2,3,4
1Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada.
Insights
Vagus nerve stimulation (VNS) in children with drug-resistant epilepsy (DRE) shows that seizure severity and frequency timescales, not just the 50% reduction threshold, significantly improve quality of life. These findings highlight a more comprehensive approach to assessing VNS effectiveness.
Area of Science:
- Pediatric Neurology
- Epilepsy Research
- Neurostimulation
Background:
- Drug-resistant epilepsy (DRE) in children poses significant challenges to management.
- Vagus nerve stimulation (VNS) is an established therapy for DRE, but its effectiveness is often narrowly defined by seizure frequency reduction.
- The impact of VNS on seizure severity and health-related quality of life (HRQoL) requires further characterization.
Purpose of the Study:
- To evaluate the effectiveness of VNS in children with DRE beyond the conventional 50% seizure reduction threshold.
- To investigate the relationship between VNS, seizure severity, seizure frequency timescales, and HRQoL.
- To identify key indicators of meaningful treatment response in pediatric DRE.
Main Methods:
- Analysis of data from 67 children (aged 0-18) with DRE treated with VNS across eight North American centers (CONNECTiVOS database).
- Prospective data collection at baseline and 6, 12, and 24 months post-VNS, assessing seizure frequency, seizure severity (Seizure Severity Questionnaire), and HRQoL (Quality of Life in Childhood Epilepsy).
- Utilized linear mixed models to analyze longitudinal changes and the impact of seizure characteristics on HRQoL.
Main Results:
- Only 37.3% of children showed reduced seizure frequency timescales, compared to 55.2% meeting the 50% reduction threshold; 17.9% met the threshold without timescale improvement.
- Significant improvements in seizure severity were observed in 31.9% of children irrespective of seizure timescale reduction.
- HRQoL gains were primarily driven by improvements in seizure frequency timescales (p=0.023) and reduced overall seizure severity (p=0.035), not the 50% threshold.
Conclusions:
- The conventional 50% responder definition inadequately captures meaningful HRQoL improvements in pediatric DRE treated with VNS.
- Seizure frequency timescales and seizure severity are more closely associated with HRQoL gains than the 50% threshold.
- A comprehensive assessment including seizure severity and frequency patterns is crucial for evaluating VNS efficacy in children with DRE.
Objectives:
Responsiveness to vagus nerve stimulation (VNS) in children with drug-resistant epilepsy (DRE) is often defined based on reduction in seizure frequency, typically at the 50% threshold, with limited consideration to the effects of therapy on seizure severity and health-related quality of life (HRQoL). In the current report, we sought to better characterize the effects of VNS beyond seizure frequency in children with DRE.
Methods:
Sixty-seven children from the Connectomic profiling and Vagus nerve stimulation Outcomes Study (CONNECTiVOS) database, a multicenter study including children aged 0-18 who underwent VNS at eight North American centers, were included. Data were collected prospectively at baseline and 6, 12, and 24 months after VNS. Seizure outcomes were assessed using the 50% threshold, percentage change in seizure count and change on a frequency timescale, a categorical measure of seizure occurrence (e.g., daily to weekly seizures). The Seizure Severity Questionnaire and the Quality of Life in Childhood Epilepsy were also collected. Linear mixed models were constructed to study longitudinal changes in seizure severity and HRQoL.
Results:
Among 67 children, 55.2% experienced >50% reduction in seizures, whereas only 37.3% demonstrated reductions in seizure timescales. Notably, 17.9% experienced no reduction in timescales despite meeting the 50% threshold. Furthermore, 31.9% of children experienced a meaningful improvement in seizure severity without any reduction in seizure timescales. HRQoL improvements were driven by the reduction in timescales (mean yearly increase of 3.65; 95% confidence interval [CI]: 0.71-6.52, p = 0.023), rather than responsiveness based on the 50% threshold or percentage change in seizure counts (p > 0.05). Reduced overall seizure severity was also independently associated with higher HRQoL after VNS (p = 0.035).
Significance:
The conventional 50% responder threshold failed to capture meaningful gains in HRQoL, which aligned more closely with seizure timescales. Furthermore, nearly one-third of children realized improvements in seizure severity without any reduction in timescales. Improvements in both seizure frequency timescales and seizure severity drive postoperative HRQoL gains.
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