Authors :
Presenting Author: Paul Lyons, MD, PhD – Virginia Comprehensive Epilepsy Program
Paul Lyons, MD PhD – Virginia Comprehensive Epilepsy Program; James Wheless, MD – Le Bonheur Children’s Hospital; Ryan Verner, PhD – LivaNova USA Inc.; Jose Ferreira, MD – St. Joseph’s Children’s Hospital; Kore Liow, MD – University of Hawai'i at Mānoa; James Valeriano, MD – Allegheny General Hospital; Gholam Motamedi, MD – Georgetown University Hospital
Rationale:
Lennox-Gastaut Syndrome (LGS) has long term impacts on the lives of patients and caregivers. People living with LGS have severe intractable epilepsy that is difficult to treat with conventional pharmacological and non-pharmacological therapies. Vagus nerve stimulation (VNS) can help manage the seizures associated with LGS. While VNS is commonly used, the prior reported efficacy data has centered primarily on retrospective reviews and the population prevalence of LGS at individual centers has limited the availability of quality prospective cohort data.
Methods: Patients were enrolled into a prospective, multicenter, multinational observational registry called CORE-VNS (NCT03529045). The registry, which is ongoing, aims to collect up to 36 months of data on seizure and non-seizure outcomes following treatment with VNS, and includes both patients receiving an initial VNS implant as well as those undergoing battery replacement. Participants were identified as having a recorded diagnosis of LGS, and those receiving initial VNS implant were identified for analysis. Baseline seizure frequency data (collected from seizure diaries) and patient reported outcome measures such as quality of life (one question Likert scale) and quality of sleep (Pittsburg Sleep Quality Index: PSQI or Children’s Sleep Habit Questionnaire: CSHQ) were collected, and follow-up of these measures were collected at 3, 6, 12, 24, and 36 months. For this interim analysis, the 12-month outcome is compared to the pre-implant baseline.
Results: Fifty-six (56) participants (31 male) in the CORE-VNS registry received an initial implant of VNS to manage their LGS symptoms. The population was geographically and ethnically diverse, with 30.4% European, 28.6% from the Americas, and 26.8% from the Western Pacific. The median age at implant was 12.44 years (range 2.2-47.6) and the study population was predominately children (71.4% vs 28.6% adult). The vast majority of participants have severe cognitive impairment (71.4%). These patients had failed to respond to a median of six anti-seizure medications (range 2-17), and most (83.9%) had not undergone epilepsy surgery. After 12 months of VNS, 62.3% (n=33) of participants had responded to therapy (
≥50% reduction in seizure frequency, all seizures) and 54.7% (n=29) had experienced a
≥80% reduction in seizure frequency.
The overall median seizure frequency reduction at 12 months was 56.7% (95% CI: 41.7%-76.7%), and while specific seizure type data were sparse, the median reduction in focal seizures was 71.3% and the median reduction in generalized seizures was 49.0%. Most subjects reported improvement in quality of life at 12 months (54.17%; n=26/48 non-missing) or no change (41.67%; n=20/48 non-missing). Overall sleep quality was not improved or worsened, on either the PSQI or CSHQ. VNS was generally well tolerated, with only nine of 56 participants (16.1%) reporting at least one treatment emergent adverse event, primarily cough, dysphonia, and oropharyngeal and/or neck pain.
Conclusions: Real world experience with VNS supports its use as an effective treatment that can improve quality of life for patients living with LGS.
Funding:
This work was funded by LivaNova USA Inc.