Authors :
Presenting Author: Muhammad Zafar, MD, FACNS – Duke University Hospital
Gholam Motamedi, MD – Medstar Georgetown University Hospital
James Wheless, BScPharm, MD, FAAP, FACP, FAAN, FAES – LeBonheur Children’s Hospital
Gaia Giannicola, PhD – LivaNova PLC
Fawzi Babtain, MBBS, MHSc, FRCPC, CSCN (EEG, EMG) – King Faisal Specialist Hospital and Research Centre- Jeddah
Saleh Baeesa, MD – King Faisal Specialist Hospital and Research Centre
Menaka Paranathala, MD – Royal Victoria Infirmary, Newcastle-upon-Tyne,
Riëm El Tahry, MD, PhD – UC Louvain
Gudrun Groeppel, MD – Kepler University Hospital
Terence J. O'Brien, MBBS, MD – Alfred Health
Paul Lyons, MD, PhD – Virginia Commonwealth Epilepsy Program
Kore Liow, MD – University of Hawaii at Manoa
Ryan Verner, PhD – LivaNova PLC (or a subsidiary)
Kathryn Nichol, PhD, MS, MBA – LivaNova PLC
Francesca Beraldi, MS – LivaNova PLC (or a subsidiary)
Charles Gordon, MS – LivaNova PLC (or a subsidiary)
Danielle Urry, MD – LivaNova PLC
Arjune Sen, MD – Oxford University
Rationale:
Vagus nerve stimulation (VNS) was approved for use in pediatric patients with drug resistant epilepsy (DRE) since 2017 and prospective, real-world evidence across this population has been limited. The CORE-VNS is a prospective open-label study of over 800 patients across 16 countries. It represents the first large cohort of prospectively gathered pediatric data on the effectiveness of responsive VNS Therapy for DRE. In this analysis, evidence at 24 months is presented for all implant naïve participants < 18 years of age.
Methods:
Participants were enrolled into a prospective, multicenter, multinational observational study-CORE-VNS (NCT03529045). This real-world study collected data on seizure and non-seizure outcomes following treatment with VNS Therapy. For this pediatric group subgroup analysis, all neuromodulation implant naïve (NIN) < 18 years of age who received a VNS Therapy implant were selected. Seizure frequency for all types of seizures reported and patient-reported outcome measures, such as quality of life and quality of sleep, were collected at baseline and 3, 6, 12, 24, and 36 months. The 24-month outcomes are compared to the pre-implant baseline and presented here.Results: 312 (54% male, 46% female) children were included. Of those who received a VNS Therapy device, 240 (77%) were considered NIN. 40.8% of all children underwent VNS Therapy in Europe, 27.5% in the Americas, and 25.8% in the Western Pacific. The median age for children receiving their first implant was 9.7 years (range 1 to 17.99) and the median duration between epilepsy diagnosis and informed consent was 5.5 years (range 0-16.5 years). The median number of prior failed anti-seizure medications (ASMs) for this group was 6 (range 2-17). In addition, 63.4% of these children had at least moderate cognitive impairment, 87.1% had no prior brain or epilepsy surgery, and 88.3% of NIN children received a responsive VNS Therapy device (i.e., SenTiva, AspireSR). With a median time to labeled target dose (combination of output current and pulse width) of 6 months, the NIN responder rate (≥50% reduction in seizure frequency) at 24 months was 53.9% (all seizures), 54.4% (generalized), and 58.7% (focal seizures). A ≥80% reduction in seizure frequency was also noted in 31.3%, 36.7%, and 39.9% for all seizures, generalized, and focal. The median seizure frequency reduction at 24 months for NIN was 55.3% across all seizures, 61.1% for focal, and 60% for generalized. Most reported either improved quality of life at 24 months (43%) or no change (44.3%). Overall sleep quality trended towards improvement as measured by CSHQ. VNS was well-tolerated, with 24.2% of NIN children reporting at least 1 treatment-emergent adverse event. 3.8% were reported as related to the investigation device or procedure. The most common ( > 5% reported) included respiratory, thoracic, and mediastinal disorders, primarily dysphonia.
Conclusions:
Adjunctive VNS Therapy reduced seizures, regardless of type, over the course of 24 months in NIN children with DRE. The majority of NIN children had a >50% reduction in seizures at 24 months. Quality of life was also improved in 43% of children and remained stable in the remaining.
Funding: LivaNova PLC.