Paul Boon1, Kristl Vonck2, Kenou van Rijckevorsel3, Riem El Tahry4, Christian E Elger5, Nandini Mullatti6, Andreas Schulze-Bonhage7, Louis Wagner8, Beate Diehl9, Hajo Hamer10, Markus Reuber11, Hrisimir Kostov12, Benjamin Legros13, Soheyl Noachtar14, Yvonne G Weber15, Volker A Coenen16, Herbert Rooijakkers17, Olaf E M G Schijns18, Richard Selway19, Dirk Van Roost20, Katherine S Eggleston21, Wim Van Grunderbeek22, Amara K Jayewardene23, Ryan M McGuire24. 1. Department of Neurology, Ghent University Hospital, 185 De Pintelaan, 9000 Ghent, Belgium. Electronic address: Paul.Boon@UGent.be. 2. Ghent University Hospital, Gent, Belgium. Electronic address: kristl.vonck@ugent.be. 3. Cliniques Universitaires St Luc, Brussels, Belgium. Electronic address: kenou.vanrijckevorsel@uclouvain.be. 4. Cliniques Universitaires St Luc, Brussels, Belgium. Electronic address: riem.eltahry@uclouvain.be. 5. University Hospital Bonn, Bonn, Germany. Electronic address: christian.elger@ukb.uni-bonn.de. 6. King's College Hospital, London, United Kingdom. Electronic address: nandini.mullatti@nhs.ne. 7. University Medical Center Freiburg, Freiburg, Germany. Electronic address: andreas.schulze-bonhage@uniklinik-freiburg.de. 8. Academic Center for Epileptology Kempenhaeghe, Heeze, The Netherlands. Electronic address: WagnerL@kempenhaeghe.nl. 9. The National Hospital for Neurology and Neurosurgery, Queen Square, London, United Kingdom. Electronic address: beate.diehl@uclh.nhs.uk. 10. University of Erlangen, Erlangen, Germany. Electronic address: hajo.hamer@uk-erlangen.de. 11. University of Sheffield, Sheffield, United Kingdom. Electronic address: Markus.Reuber@sth.nhs.uk. 12. Oslo University Hospital, Oslo, Norway. Electronic address: hrisimik@ous-hf.no. 13. Université Libre de Bruxelles, Brussels, Belgium. Electronic address: blegros@ulb.ac.be. 14. Ludwig Maximilian University of Munich, Munich, Germany. Electronic address: soheyl.noachtar@med.uni-muenchen.de. 15. University of Tübingen, Tübingen, Germany. Electronic address: yvonne.Weber@uni-tuebingen.de. 16. University Medical Center Freiburg, Freiburg, Germany. Electronic address: volker.coenen@uniklinik-freiburg.de. 17. Université Catholique de Louvain, Brussels, Belgium. Electronic address: herbert.rooijakkers@uclouvain.be. 18. Academic Center for Epileptology Kempenhaeghe, Heeze, The Netherlands; Department of Neurosurgery, Maastricht University Medical Center, Maastricht, The Netherlands. Electronic address: o.schijns@mumc.nl. 19. King's College Hospital, London, United Kingdom. Electronic address: richard.selway@nhs.net. 20. Ghent University Hospital, Gent, Belgium. Electronic address: dirk.vanroost@ugent.be. 21. Cyberonics, Inc., Houston, TX, United States. Electronic address: katherine.eggleston@cyberonics.com. 22. Cyberonics Europe, Brussels, Belgium. Electronic address: wim.vangrunderbeek@cyberonics.com. 23. Cyberonics, Inc., Houston, TX, United States. Electronic address: amara.jayewardene@cyberonics.com. 24. Cyberonics, Inc., Houston, TX, United States. Electronic address: ryan.mcguire@cyberonics.com.
Abstract
PURPOSE: 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.
RCT Entities:
PURPOSE: 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 epilepsypatients.
Authors: Daniel M Goldenholz; Robert Moss; David A Jost; Nathan E Crone; Gregory Krauss; Rosalind Picard; Chiara Caborni; Jose E Cavazos; John Hixson; Tobias Loddenkemper; Tracy Dixon Salazar; Laura Lubbers; Lauren C Harte-Hargrove; Vicky Whittemore; Jonas Duun-Henriksen; Eric Dolan; Nitish Kasturia; Mark Oberemk; Mark J Cook; Mark Lehmkuhle; Michael R Sperling; Patricia O Shafer Journal: Epilepsia Date: 2018-03-31 Impact factor: 5.864
Authors: C Á Szabó; F S Salinas; A M Papanastassiou; J Begnaud; M Ravan; K S Eggleston; R Shade; C Lutz; M De La Garza Journal: Epilepsy Res Date: 2017-10-12 Impact factor: 3.045
Authors: A Schulze-Bonhage; S Böttcher; M Glasstetter; N Epitashvili; E Bruno; M Richardson; K V Laerhoven; M Dümpelmann Journal: Nervenarzt Date: 2019-12 Impact factor: 1.214