What defines response to vagus nerve stimulation in children with drug-resistant epilepsy? A prospective cohort study from the CONNECTiVOS collaboration

Farbod Niazi^{1

2}, Karim Mithani^{2

3

4}, Hrishikesh Suresh^{2

3

4}, Simeon M Wong^{2

4}, Ivanna Yau⁵, Lyndsey McRae⁵, Thiemo F Dinger^{2

3}, James T Rutka^{2

3}, Ayako Ochi⁵, Hiroshi Otsubo⁵, Shelly Weiss⁵, Lauren Sham⁵, Elizabeth Donner⁵, Vann Chau⁵, Aristides Hadjinicolaou⁶, Philippe Major⁶, Alexander G Weil⁷, Jignesh Tailor⁸, Taylor J Abel⁹, Madison Remick⁹, Emefa Akwayena⁹, Dewi Schrader¹⁰, Robert J Bollo¹¹, Matthew D Smyth¹², Diana Aum¹², Sean Lew¹³, Shelly Wang¹⁴, Toba Niazi¹⁴, Jeffrey S Raskin¹⁵, Elysa Widjaja¹⁶, Howard L Weiner¹⁷, Nisha Gadgil¹⁷, Melissa A LoPresti¹⁸, Gregory W Albert¹⁹, Aria Fallah²⁰, Elizabeth Kerr²¹, Mary Lou Smith^{2

21

22}, Puneet Jain⁵, George M Ibrahim^{2

3

4}

Affiliations

¹ Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada.
² Neurosciences and Mental Health, SickKids Research Institute, Toronto, Ontario, Canada.
³ Division of Neurosurgery, The Hospital for Sick Children, Toronto, Ontario, Canada.
⁴ Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.
⁵ Division of Neurology, The Hospital for Sick Children, Toronto, Ontario, Canada.
⁶ Division of Neurology, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada.
⁷ Division of Neurosurgery, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada.
⁸ Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, Indiana, USA.
⁹ Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
¹⁰ Department of Pediatrics, British Columbia Children's Hospital, Vancouver, British Columbia, Canada.
¹¹ Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake, Utah, USA.
¹² Division of Neurosurgery, Johns Hopkins All Children's Hospital, St. Petersburg, Florida, USA.
¹³ Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
¹⁴ Department of Neurosurgery, Nicklaus Children's Hospital, Miami, Florida, USA.
¹⁵ Division of Pediatric Neurosurgery, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA.
¹⁶ Department of Medical Imaging, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA.
¹⁷ Division of Pediatric Neurosurgery, Department of Surgery, Texas Children's Hospital, Houston, Texas, USA.
¹⁸ Department of Neurosurgery, University of Rochester Medical Center, Rochester, New York, USA.
¹⁹ Arkansas Children's Hospital, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
²⁰ Department of Neurosurgery, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California, USA.
²¹ Department of Psychology, Hospital for Sick Children, Toronto, Ontario, Canada.
²² Department of Psychology, University of Toronto Mississauga, Mississauga, Ontario, Canada.

PMID: 40574479
DOI: 10.1111/epi.18520

What defines response to vagus nerve stimulation in children with drug-resistant epilepsy? A prospective cohort study from the CONNECTiVOS collaboration

Farbod Niazi et al. Epilepsia. 2025.

. 2025 Jun 26.

doi: 10.1111/epi.18520. Online ahead of print.

Authors

Affiliations

¹ Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada.
² Neurosciences and Mental Health, SickKids Research Institute, Toronto, Ontario, Canada.
³ Division of Neurosurgery, The Hospital for Sick Children, Toronto, Ontario, Canada.
⁴ Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.
⁵ Division of Neurology, The Hospital for Sick Children, Toronto, Ontario, Canada.
⁶ Division of Neurology, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada.
⁷ Division of Neurosurgery, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada.
⁸ Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, Indiana, USA.
⁹ Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
¹⁰ Department of Pediatrics, British Columbia Children's Hospital, Vancouver, British Columbia, Canada.
¹¹ Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake, Utah, USA.
¹² Division of Neurosurgery, Johns Hopkins All Children's Hospital, St. Petersburg, Florida, USA.
¹³ Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
¹⁴ Department of Neurosurgery, Nicklaus Children's Hospital, Miami, Florida, USA.
¹⁵ Division of Pediatric Neurosurgery, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA.
¹⁶ Department of Medical Imaging, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA.
¹⁷ Division of Pediatric Neurosurgery, Department of Surgery, Texas Children's Hospital, Houston, Texas, USA.
¹⁸ Department of Neurosurgery, University of Rochester Medical Center, Rochester, New York, USA.
¹⁹ Arkansas Children's Hospital, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
²⁰ Department of Neurosurgery, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California, USA.
²¹ Department of Psychology, Hospital for Sick Children, Toronto, Ontario, Canada.
²² Department of Psychology, University of Toronto Mississauga, Mississauga, Ontario, Canada.

PMID: 40574479
DOI: 10.1111/epi.18520

Abstract

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.

Keywords: drug‐resistant; epilepsy; epilepsy surgery; pediatric epilepsy; quality of life; vagus nerve stimulation.

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References

REFERENCES

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What defines response to vagus nerve stimulation in children with drug-resistant epilepsy? A prospective cohort study from the CONNECTiVOS collaboration

Affiliations

What defines response to vagus nerve stimulation in children with drug-resistant epilepsy? A prospective cohort study from the CONNECTiVOS collaboration

Authors

Affiliations

Abstract

References

REFERENCES

Grants and funding

LinkOut - more resources

Full Text Sources