Vagus nerve stimulation for drug-resistant epilepsy: A
European long-term study up to 24 months in 347 children
*Iren Orosz, †David McCormick, ‡Nelia Zamponi, §Sophia Varadkar, ¶Martha Feucht,
#Dominique Parain, **Roger Griens, ††Louis Vall ee, ‡‡Paul Boon, §§Christopher Rittey,
¶¶Amara K. Jayewardene, ¶¶Mark Bunker, ##Alexis Arzimanoglou, and ***Lieven Lagae
Epilepsia, 55(10):1576–1584, 2014
doi: 10.1111/epi.12762
Dr. Iren Orosz is a
pediatric neurologist at
the Pediatric Clinic of
the Medical University
of L€ ubeck, Germany
and currently works as
a Visiting Assistant
Professor in the
Department of
Radiological Sciences
at the David Geffen
School of Medicine at
University California
Los Angeles.
SUMMARY
Objective: To gain insight into the long-term impact of vagus nerve stimulation (with
VNS Therapy) in children with drug-resistant epilepsy, we conducted the largest retro-
spective multicenter study to date over an extended follow-up period of up to 24 months.
Methods: The primary objective was to assess change in seizure frequency of the pre-
dominant seizure type (defined as the most disabling seizure) following VNS device
implantation. Treating physicians collected data from patient records from baseline to
6, 12, and 24 months of follow-up.
Results: The analysis population included 347 children (aged 6 months to 17.9 years
at the time of implant). At 6, 12, and 24 months after implantation, 32.5%, 37.6%, and
43.8%, respectively, of patients had ≥50% reduction in baseline seizure frequency of
the predominant seizure type. The responder rate was higher in a subgroup of patients
who had no change in antiepileptic drugs (AEDs) during the study. Favorable results
were also evident for all secondary outcome measures including changes in seizure
duration, ictal severity, postictal severity, quality of life, clinical global impression of
improvement, and safety. Post hoc analyses demonstrated a statistically significant
correlation between VNS total charge delivered per day and an increase in response
rate. VNS Therapy is indicated as adjunctive therapy in children with focal, structural
epilepsies, who for any reason are not good candidates for surgical treatment following
the trial of two or more AEDs. Children with predominantly generalized seizures from
genetic, structural epilepsies, like Dravet syndrome or Lennox-Gastaut syndrome,
could also benefit from VNS Therapy.
Significance: The results demonstrate that adjunctive VNS Therapy in children with
drug-resistant epilepsy reduces seizure frequency and is well tolerated over a 2-year
follow-up period. No new safety issues were identified. A post hoc analysis revealed a
dose–response correlation for VNS in patients with epilepsy.
KEY WORDS: Clinical trial, Epilepsy, Pediatrics, Quality of life, Vagus nerve
stimulation.
Accepted July 22, 2014; Early View publication September 17, 2014.
*Department of Neuropediatrics, Children's Hospital, University of Leubeck, Leubeck, Germany; †King's College Hospital, London, United
Kingdom; ‡Department of Pediatric Neurology, Riuniti Hospital, Ancona, Italy; §UCL Institute of Child Health, Great Ormond Street Hospital for
Children NHS Foundation Trust, London, United Kingdom; ¶Department of Pediatric Neurology, University of Medicine, Wien, Vienna, Austria;
#Charles Nicolle Department of Neurophysiology, Rouen University Hospital, Rouen, France; **Medisch Spectrum Twente, Enschede, The
Netherlands; ††Pole Child Neuropediatrics Service, Roger-Salengro Hospital, CHRU-University of North France, Lille, France; ‡‡Department of
Neurology, Ghent University Hospital, Ghent, Belgium; §§Sheffield Children's Hospital, Sheffield, United Kingdom; ¶¶Cyberonics, Inc., Houston,
Texas, U.S.A.; ##Epilepsy, Sleep and Pediatric Neurophysiology Department, University Hospitals of Lyon (HCL) and Lyon Neurosciences Research
Center (CRNL), Lyon, France; and ***Gasthuisberg University Hospital, Leuven, Belgium
Address correspondence to Lieven Lagae, Department of Pediatric Neurology, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium.
E-mail: lieven.lagae@uzleuven.be and Alexis Arzimanoglou, Epilepsy, Sleep, and Pediatric Neurophysiology Department, HFME – University Hospitals
of Lyon (HCL), 59 Boulevard Pinel, 69677 Lyon, France. E-mail: aarzimanoglou@orange.fr
Wiley Periodicals, Inc.
© 2014 International League Against Epilepsy
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FULL-LENGTH ORIGINAL RESEARCH