Abstracts

Rationale: Brain-responsive neurostimulation has been demonstrated to be safe and effective in reducing the frequency of medically intractable focal-onset seizures (FOS) in adults with medically refractory focal epilepsy (Heck et al., 2014). In clinical trials, treatment resulted in improvements in mood and multiple domains of quality of life (QOL) (Meador et al., 2015). Because frequent FOS can be associated with progressive impairments in mood and QOL, we hypothesized that patients who had a shorter duration of epilepsy before beginning treatment with brain-responsive neurostimulation might also have greater improvements in mood and QOL. Methods: All patients were treated with brain-responsive stimulation while participating in prospective clinical trials of the RNS System (NeuroPace, Mountain View, CA). FOS frequency was obtained from patient-maintained seizure diaries, and reductions in FOS frequency were computed as a percentage relative to baseline. Percent reductions in FOS frequency were not normally distributed, so they were compared across groups using the Mann-Whitney U-test. Mood was assessed using the Beck Depression Inventory-II (BDI), and QOL was assessed using the Quality of Life in Epilepsy Inventory (QOLIE-89) overall score and the derived epilepsy-targeted, cognitive, mental, and physical subscales. For each patient, baseline scores (3-months pre-treatment) were compared to treatment year 2 for the BDI and to treatment year 8 for the QOLIE. Changes in mood and QOL scores were computed for patients who began treatment “early” (within 20 years of onset) and those who began treatment “late” (after 20 years of onset). Mood and QOL score changes were normally distributed; thus, paired 2-tailed T-tests were used to test for a significant change in each score for each group, and two-sample 1-tailed T-tests were used to test for differences between groups. Results: Seizure rate reductions were comparable between the early and late-treatment groups. Namely, patients in the early-treatment group who completed the QOL assessment at both timepoints (N = 67) had a median (inter-quartile range) reduction in seizure rates of 70.0 (62.7)% across those 8 years, compared to 73.3 (44.6)% in the late-treatment patients (N = 76). Patients in the early-treatment group who completed the mood assessment at both timepoints (N = 73) had a median seizure rate reduction of 53.9 (71.1)% across those 2 years, compared to a 55.0 (60.3)% reduction in the late-treatment group (N = 70). However, the early and late-treatment groups differed in their QOL and mood improvements (see Figure). Namely, improvements were significantly greater in the early treatment group than the late treatment group for mood and every QOL outcome measure (except the epilepsy-targeted QOL domain, in which both groups improved). The early-treatment patients had significant improvements in mood and in all domains of QOL (except the QOLIE-Mental domain, for which improvement was not significant). In contrast, patients in the late-treatment group had no significant improvements in mood nor any aspect of QOL, other than the epilepsy-targeted domain. Conclusions: Patients treated with brain-responsive stimulation earlier in the course of their epilepsy had significant improvements in mood and multiple domains of QOL that were not seen in patients treated later in the course of their epilepsy, despite similar durations of treatment and improvements in seizure rates across the 2 groups. These results suggest that early intervention maximizes the opportunity for improvements in mood and QOL; if treatment is delayed for too long, improvements in mood and QOL may no longer be possible. Funding: No funding