Abstracts

Rationale: Lennox-Gastaut Syndrome (LGS) is a severe generalized epilepsy in an ongoing feasibility trial with the RNS® System (NCT05339126). LGS is a debilitating form of epilepsy that typically begins in childhood and persists into adulthood, characterized by multiple seizure types. Seizures are often frequent and severe, which can lead to falls and injuries. Individuals with LGS often face developmental delays, intellectual disability, and behavioral problems. This significantly impacts the quality of patients and caregivers, making effective treatment strategies crucial. This feasibility trial aims to generate preliminary safety and effectiveness data for brain-responsive neurostimulation as an adjunctive therapy in reducing the frequency of seizures in individuals aged 12 years or older with LGS who are refractory to antiseizure medications.

Methods: The trial is a prospective randomized single-blind cross-over study, with follow-up for 2 years post-implant. The consecutive trial periods are: pre-implant baseline, post-op, blinded evaluation, open label and long-term follow-up. To assess preliminary safety and effectiveness of the two active stimulation conditions (high-frequency short bursts, low-frequency long bursts), and of a blinded sham stimulation condition, clinical assessments are conducted, including a daily seizure diary and study visit assessments of affect, cognition, and patient quality of life. The trial also assesses caregiver burden and global impression of change from patient, caregiver, and clinician perspectives.

Results: As of June 2024, 16 of planned 20 subjects with LGS, aged between 15-51 (mean age 26), have been enrolled across 6 study sites. Among 16 subjects, 6 are female (37.5%). The mean age of epilepsy diagnosis was 5 years (range: under 1-18). At enrollment, mean number of antiseizure drugs was 5 (range: 4-8). During pre-implant baseline (30-days), subjects had an average of 45 drop seizures. Additional baseline characteristics will be presented.

Due to developmental and intellectual capabilities, many patient-specific assessments could not be completed, including neuropsychological evaluation from NIH toolbox cognition battery, and the Quality of Life in Epilepsy survey. Consequently, seizure diary data, caregiver, and clinician reports serve as primary baseline benchmarks.

Conclusions: Standard measurements used to assess cognitive, behavioral, and affect changes in patients with epilepsy often fall short when applied to patients with LGS. The developmental and intellectual challenges associated with LGS make it difficult to complete these traditional assessments. This highlights the need for a shift in how outcomes are evaluated for this patient populations. Shifting the focus towards more holistic and developmentally appropriate measures and examining the value of a therapy beyond seizure response may lead to more effective treatment strategies, improved quality of life, and reduced caregiver burden.

Funding: NIH NINDS UH3NS109557