Abstracts

Long-term Adjunctive VNS Therapy Use in Patients with Genetic Epilepsy – 24 M CORE-VNS Outcomes

Abstract number : 1.517
Submission category : 4. Clinical Epilepsy / 4C. Clinical Treatments
Year : 2024
Submission ID : 1498
Source : www.aesnet.org
Presentation date : 12/7/2024 12:00:00 AM
Published date :

Authors :
Presenting Author: Nicola Specchio, MD, PhD – Bambino Gesu’ Children’s Hospital, IRCCS, Full Member of European Reference Network on Rare and Complex Epilepsies EpiCARE

Jose Ferreira, MD – Pediatric Epilepsy and Neurology Specialists, Tampa, Florida, USA
Michal Tzadok, MD – Safra Children's Hospital, Sheba Medical Center
Hadassa Goldberg-Stern, MD – Institute of Pediatric Neurology, Schneider Children's Medical Center of Israel, Petah, Tiqva, Israel
David McCormick, MD – Kings's College Hospital, London, England, United Kingdom
Barbara Mostacci, MD – Istituto delle Scienze Neurologiche di Bologna, Full Member of European Reference Network on Rare and Complex Epilepsies EpiCARE, Bologna, Italy
Youssef Al-Said, MD – Department of Neurosciences, King Faisal Specialist Hospital & Research Center, Jeddah, Saudi Arabia
Maxine Dibue, PhD – LivaNova PLC
Gaia Giannicola, PhD – LivaNova PLC
Paolo Tinuper, MD – Istituto delle Scienze Neurologiche di Bologna, Full Member of European Reference Network on Rare and Complex Epilepsies EpiCARE, Bologna, Italy
Francesca Beraldi, MS – LivaNova PLC (or a subsidiary)

Rationale:

Genetic epilepsies, including developmental and epileptic encephalopathies (DEE), are often characterized by early-onset, severe, drug-resistant seizures. Genetic DEEs are rare and diverse in terms of incidence and genetic variants; therefore, evaluating the efficacy of treatments can be challenging. The analysis aims to assess the effectiveness of adjunctive vagus nerve stimulation (VNS) Therapy in reducing seizures and improving quality of life (QoL) in patients with genetic epilepsies in the CORE-VNS study.



Methods:

Participants were enrolled in a prospective, multicenter, multinational observational study- CORE-VNS (NCT03529045), which assesses the impact of VNS Therapy in a real-world setting in drug-resistant epilepsy patients across all age groups and epilepsy etiologies. For this analysis, participants with confirmed genetic epilepsy (CGE) who received VNS Therapy were selected. Baseline seizure frequency data and patient-reported outcome measures, such as QoL, were analyzed at baseline, 3, 6, 12, 24, and 36 months. The 24-month outcomes following VNS implantation in neuromodulation implant naïve (NIN) patients are compared to the pre-implant baseline and are presented here.



Results:

252 participants in the CORE-VNS study were suspected at baseline to have a genetic epilepsy etiology and therefore underwent testing. Genetic epilepsy was confirmed in 45% (n=114), 82 of which were NIN. The median age at VNS implant in patients with confirmed CGE was 8.33 (range 1-55) years versus 27.93 (range 1-71) years for those not tested. The median duration between epilepsy diagnosis and informed consent was 6.5    and 12.5 years for patients with CGE versus those not tested, respectively.  The median number of failed anti-seizure medications (ASMs) in the CGE group was 7 (range 3 to 20)  and 76.8%  had at least moderate cognitive impairment. At 24 months, 57.9% of patients with CGE were responders ( >50% seizure-frequency reduction) compared to 50.9% of patients who did not undergo genetic testing. In patients with CGE the median percentage change in seizure frequency at 24 months was -60% (95%CI -74.8 to -43.6) for all seizures, -70.5% (95%CI -93.3 to -57.1) for all focal seizures, and -60% (95%CI -100 to -10) for all generalized seizures. For CGE patients with generalized tonic-clonic seizures (GTCs), a reduction of -85.7 (-110 to -10) was noted. The percentage of patients rating their QoL as pretty good or very good increased from 24.4% at baseline to 48.4%.  Seizure frequency and ASM burden impacted QoL less at 24 months. The most common treatment-emergent adverse event in patients with CGE was cough at 6.1%.



Conclusions: Genetic testing and a positive genetic test were associated with earlier use of VNS Therapy. The response of patients with CGE to VNS was robust and comparable to that of patients who did not undergo genetic testing. VNS Therapy was associated with an improvement of QoL in patients with confirmed genetic epilepsies.

Funding:

The CORE-VNS study was supported by LivaNova PLC.



Clinical Epilepsy