title: A prospective, multicenter study of cardiac-based seizure detection to activate vagus nerve stimulation.
abstract: OBJECTIVE
  This study investigates the performance of a cardiac-based seizure detection algorithm (CBSDA) that automatically triggers VNS (NCT01325623).
  
  
  METHODS
  Thirty-one patients with drug resistant epilepsy were evaluated in an epilepsy monitoring unit (EMU) to assess algorithm performance and near-term clinical benefit. Long-term efficacy and safety were evaluated with combined open and closed-loop VNS.
  
  
  RESULTS
  Sixty-six seizures (n=16 patients) were available from the EMU for analysis. In 37 seizures (n=14 patients) a ≥ 20% heart rate increase was found and 11 (n=5 patients) were associated with ictal tachycardia (iTC, 55% or 35 bpm heart rate increase, minimum of 100 bpm). Multiple CBSDA settings achieved a sensitivity of ≥ 80%. False positives ranged from 0.5 to 7.2/h. 27/66 seizures were stimulated within ± 2 min of seizure onset. In 10/17 of these seizures, where triggered VNS overlapped with ongoing seizure activity, seizure activity stopped during stimulation. Physician-scored seizure severity (NHS3-scale) showed significant improvement for complex partial seizures (CPS) at EMU discharge and through 12 months (p<0.05). Patient-scored seizure severity (total SSQ score) showed significant improvement at 3 and 6 months. Quality of life (total QOLIE-31-P score) showed significant improvement at 12 months. The responder rate (≥ 50% reduction in seizure frequency) at 12 months was 29.6% (n=8/27). Safety profiles were comparable to prior VNS trials.
  
  
  CONCLUSIONS
  The investigated CBSDA has a high sensitivity and an acceptable specificity for triggering VNS. Despite the moderate effects on seizure frequency, combined open- and closed-loop VNS may provide valuable improvements in seizure severity and QOL in refractory epilepsy patients.
authors.affiliation: Department of Neurology, Ghent University Hospital, 185 De Pintelaan, 9000 Ghent, Belgium. Electronic address: Paul.Boon@UGent.be.
authors.forename: Paul
authors.initials: P
authors.lastname: Boon
authors.affiliation: Ghent University Hospital, Gent, Belgium. Electronic address: kristl.vonck@ugent.be.
authors.forename: Kristl
authors.initials: K
authors.lastname: Vonck
authors.affiliation: Cliniques Universitaires St Luc, Brussels, Belgium. Electronic address: kenou.vanrijckevorsel@uclouvain.be.
authors.forename: Kenou
authors.initials: K
authors.lastname: van Rijckevorsel
authors.affiliation: Cliniques Universitaires St Luc, Brussels, Belgium. Electronic address: riem.eltahry@uclouvain.be.
authors.forename: Riem
authors.initials: R
authors.lastname: El Tahry
authors.affiliation: University Hospital Bonn, Bonn, Germany. Electronic address: christian.elger@ukb.uni-bonn.de.
authors.forename: Christian E
authors.initials: CE
authors.lastname: Elger
authors.affiliation: King's College Hospital, London, United Kingdom. Electronic address: nandini.mullatti@nhs.ne.
authors.forename: Nandini
authors.initials: N
authors.lastname: Mullatti
authors.affiliation: University Medical Center Freiburg, Freiburg, Germany. Electronic address: andreas.schulze-bonhage@uniklinik-freiburg.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schulze-Bonhage
authors.affiliation: Academic Center for Epileptology Kempenhaeghe, Heeze, The Netherlands. Electronic address: WagnerL@kempenhaeghe.nl.
authors.forename: Louis
authors.initials: L
authors.lastname: Wagner
authors.affiliation: The National Hospital for Neurology and Neurosurgery, Queen Square, London, United Kingdom. Electronic address: beate.diehl@uclh.nhs.uk.
authors.forename: Beate
authors.initials: B
authors.lastname: Diehl
authors.affiliation: University of Erlangen, Erlangen, Germany. Electronic address: hajo.hamer@uk-erlangen.de.
authors.forename: Hajo
authors.initials: H
authors.lastname: Hamer
authors.affiliation: University of Sheffield, Sheffield, United Kingdom. Electronic address: Markus.Reuber@sth.nhs.uk.
authors.forename: Markus
authors.initials: M
authors.lastname: Reuber
authors.affiliation: Oslo University Hospital, Oslo, Norway. Electronic address: hrisimik@ous-hf.no.
authors.forename: Hrisimir
authors.initials: H
authors.lastname: Kostov
authors.affiliation: Université Libre de Bruxelles, Brussels, Belgium. Electronic address: blegros@ulb.ac.be.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Legros
authors.affiliation: Ludwig Maximilian University of Munich, Munich, Germany. Electronic address: soheyl.noachtar@med.uni-muenchen.de.
authors.forename: Soheyl
authors.initials: S
authors.lastname: Noachtar
authors.affiliation: University of Tübingen, Tübingen, Germany. Electronic address: yvonne.Weber@uni-tuebingen.de.
authors.forename: Yvonne G
authors.initials: YG
authors.lastname: Weber
authors.affiliation: University Medical Center Freiburg, Freiburg, Germany. Electronic address: volker.coenen@uniklinik-freiburg.de.
authors.forename: Volker A
authors.initials: VA
authors.lastname: Coenen
authors.affiliation: Université Catholique de Louvain, Brussels, Belgium. Electronic address: herbert.rooijakkers@uclouvain.be.
authors.forename: Herbert
authors.initials: H
authors.lastname: Rooijakkers
authors.affiliation: Academic Center for Epileptology Kempenhaeghe, Heeze, The Netherlands; Department of Neurosurgery, Maastricht University Medical Center, Maastricht, The Netherlands. Electronic address: o.schijns@mumc.nl.
authors.forename: Olaf E M G
authors.initials: OE
authors.lastname: Schijns
authors.affiliation: King's College Hospital, London, United Kingdom. Electronic address: richard.selway@nhs.net.
authors.forename: Richard
authors.initials: R
authors.lastname: Selway
authors.affiliation: Ghent University Hospital, Gent, Belgium. Electronic address: dirk.vanroost@ugent.be.
authors.forename: Dirk
authors.initials: D
authors.lastname: Van Roost
authors.affiliation: Cyberonics, Inc., Houston, TX, United States. Electronic address: katherine.eggleston@cyberonics.com.
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Eggleston
authors.affiliation: Cyberonics Europe, Brussels, Belgium. Electronic address: wim.vangrunderbeek@cyberonics.com.
authors.forename: Wim
authors.initials: W
authors.lastname: Van Grunderbeek
authors.affiliation: Cyberonics, Inc., Houston, TX, United States. Electronic address: amara.jayewardene@cyberonics.com.
authors.forename: Amara K
authors.initials: AK
authors.lastname: Jayewardene
authors.affiliation: Cyberonics, Inc., Houston, TX, United States. Electronic address: ryan.mcguire@cyberonics.com.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: McGuire
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D000069279:Drug Resistant Epilepsy / Q000175:diagnosis* / Q000503:physiopathology / Q000628:therapy*; D004562:Electrocardiography; D004569:Electroencephalography; D005260:Female; D005500:Follow-Up Studies; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010363:Pattern Recognition, Automated / Q000379:methods; D011446:Prospective Studies; D011788:Quality of Life; D012640:Seizures / Q000175:diagnosis* / Q000503:physiopathology / Q000628:therapy*; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013610:Tachycardia / Q000503:physiopathology; D055536:Vagus Nerve Stimulation / Q000009:adverse effects / Q000379:methods*; D055815:Young Adult
keywords: Cardiac based seizure detection; Ictal tachycardia; Quality of life; Refractory epilepsy; Vagus nerve stimulation