Abstracts

Rationale: The RNS® System is a direct brain responsive neurostimulation therapy approved by the U.S. FDA for the adjunctive treatment of adults with medically intractable partial onset seizures (POS). To assess whether specific antiepileptic medications (AEDs) are associated with a more favorable clinical response in patients being treated with responsive neurostimulation, an analysis was conducted to assess the change in seizure frequency when patients receiving direct brain responsive stimulation started a new AED. Methods: Patients were identified who started a new AED during an open-label period of a RNS System clinical trial and remained on a stable dose for ≥3 months. Clinical seizure rates (CSR) were calculated based on the total number of simple partial motor, complex partial and secondarily generalized tonic-clonic seizures as recorded in patient seizure diaries. Comparisons of the CSR were made between 1) the 3-months immediately preceding the AED (PRE) and the pre-implant baseline (PRE: Baseline), and 2) the first 3 months on the AED (AED3M) and the pre-implant baseline (AED3M: Baseline). An additional comparison between AED3M and PRE was performed to further assess the change in CSR attributable to the new AED. Only patients who had at least 70 days of seizure diary data in the analysis windows were included. The % change in the CSR was calculated for the two comparisons ((((PRE or AED3M)-Baseline)/(PRE or AED3M))*100). The responder rate attributable to the AED (AED-RR), independent of the response to neurostimulation, was calculated as the proportion of patients who had a ≥50% reduction in CSR during AED3M compared to PRE. Results: The four most commonly added AEDs were clobazam (CLB, n=41), lacosamide (LAC, n=96), levetiracetam (LEV, n=31), and pregabalin (PGB, n=25). Figure 1 shows the median percent change and interquartile range (IQR) in CSR for patients who started CLB, LAC, LEV, and PGB. The light blue bars show the CSR changes in response to RNS System therapy before the new AED was started (PRE:Baseline) and the dark blue bars show the CSR changes when the new AED was added  to RNS System therapy (AED3M:Baseline). There was a statistically significant additional reduction in CSR when CLB or LEV were added to treatment with the RNS System, but not when LAC and PGB were added. Further, the AED-RR was 53.7% (22/41) for CLO and 51.6% (16/31) for LEV but only 18.8% (18/96) for LAC and 12% (3/25) for PGB. Conclusions: These results suggest that patients with POS treated with responsive neurostimulation may experience additional clinical benefit when treated with specific AEDs. CLB and LEV significantly improved the clinical response already achieved with brain responsive neurostimulation, as assessed by CSR, in contrast to LAC and PGB, which did not. This raises the possibility that certain AEDs could act synergistically with neurostimulation. Whether there is a potential for synergism between neurostimulation and specific AEDs, and whether any effect is related to the AED mechanism of action, warrants further investigation. Funding: None.