Evidence map›Paper›PMID 40574479›Full record

ArticleEpilepsia2025

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

Farbod Niazi, Karim Mithani, Hrishikesh Suresh, Simeon M Wong, Ivanna Yau, Lyndsey McRae, Thiemo F Dinger, James T Rutka, Ayako Ochi, Hiroshi Otsubo and 29 more

Abstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Epilepsia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

39 authors.

Farbod NiaziFaculty of Medicine, Université de Montréal, Montreal, Quebec, Canada.ORCID https://orcid.org/0000-0001-9896-1616
Karim MithaniNeurosciences and Mental Health, SickKids Research Institute, Toronto, Ontario, Canada.ORCID https://orcid.org/0000-0002-8094-3070
Hrishikesh SureshNeurosciences and Mental Health, SickKids Research Institute, Toronto, Ontario, Canada.
Simeon M WongNeurosciences and Mental Health, SickKids Research Institute, Toronto, Ontario, Canada.ORCID https://orcid.org/0000-0001-9070-0665
Ivanna YauDivision of Neurology, The Hospital for Sick Children, Toronto, Ontario, Canada.ORCID https://orcid.org/0000-0002-8549-9618
Lyndsey McRaeDivision of Neurology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Thiemo F DingerNeurosciences and Mental Health, SickKids Research Institute, Toronto, Ontario, Canada.
James T RutkaNeurosciences and Mental Health, SickKids Research Institute, Toronto, Ontario, Canada.
Ayako OchiDivision of Neurology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Hiroshi OtsuboDivision of Neurology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Shelly WeissDivision of Neurology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Lauren ShamDivision of Neurology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Elizabeth DonnerDivision of Neurology, The Hospital for Sick Children, Toronto, Ontario, Canada.ORCID https://orcid.org/0000-0003-1126-0548
Vann ChauDivision of Neurology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Aristides HadjinicolaouDivision of Neurology, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada.
Philippe MajorDivision of Neurology, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada.
Alexander G WeilDivision of Neurosurgery, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada.ORCID https://orcid.org/0000-0003-4162-6096
Jignesh TailorDepartment of Neurological Surgery, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Taylor J AbelDepartment of Neurological Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.ORCID https://orcid.org/0000-0002-5089-460X
Madison RemickDepartment of Neurological Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Emefa AkwayenaDepartment of Neurological Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Dewi SchraderDepartment of Pediatrics, British Columbia Children's Hospital, Vancouver, British Columbia, Canada.
Robert J BolloDepartment of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake, Utah, USA.
Matthew D SmythDivision of Neurosurgery, Johns Hopkins All Children's Hospital, St. Petersburg, Florida, USA.
Diana AumDivision of Neurosurgery, Johns Hopkins All Children's Hospital, St. Petersburg, Florida, USA.ORCID https://orcid.org/0000-0001-5210-3595
Sean LewDepartment of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Shelly WangDepartment of Neurosurgery, Nicklaus Children's Hospital, Miami, Florida, USA.
Toba NiaziDepartment of Neurosurgery, Nicklaus Children's Hospital, Miami, Florida, USA.
Jeffrey S RaskinDivision of Pediatric Neurosurgery, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA.
Elysa WidjajaDepartment of Medical Imaging, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA.ORCID https://orcid.org/0000-0003-0986-5476
Howard L WeinerDivision of Pediatric Neurosurgery, Department of Surgery, Texas Children's Hospital, Houston, Texas, USA.
Nisha GadgilDivision of Pediatric Neurosurgery, Department of Surgery, Texas Children's Hospital, Houston, Texas, USA.
Melissa A LoPrestiDepartment of Neurosurgery, University of Rochester Medical Center, Rochester, New York, USA.
Gregory W AlbertArkansas Children's Hospital, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Aria FallahDepartment of Neurosurgery, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California, USA.ORCID https://orcid.org/0000-0002-9703-0964
Elizabeth KerrDepartment of Psychology, Hospital for Sick Children, Toronto, Ontario, Canada.
Mary Lou SmithNeurosciences and Mental Health, SickKids Research Institute, Toronto, Ontario, Canada.ORCID https://orcid.org/0000-0002-1937-1026
Puneet JainDivision of Neurology, The Hospital for Sick Children, Toronto, Ontario, Canada.ORCID https://orcid.org/0000-0002-6009-0859
George M IbrahimNeurosciences and Mental Health, SickKids Research Institute, Toronto, Ontario, Canada.ORCID https://orcid.org/0000-0001-9068-8184

Funding

Abe Bresver Chair in Functional NeurosurgeryCIHR PJT159561LivaNova
6 · The paper itself

Abstract

objectivesResponsiveness 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.

methodsSixty-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.

resultsAmong 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.

Indexed as

Drug Resistant EpilepsyVagus Nerve StimulationAdolescentChildChild, PreschoolCohort StudiesFemaleHumansInfantMaleProspective StudiesQuality of LifeTreatment Outcomedrug‐resistantepilepsyepilepsy surgerypediatric epilepsyquality of lifevagus nerve stimulation

Identifiers

PMID40574479
PMCPMC12605625

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.