Abstracts

Rationale: The RNS System is an FDA approved therapy that provides brain responsive stimulation for the treatment of medically intractable partial onset epilepsy. In order to optimize signal to noise ratios for detection of neural activity, the neurostimulator is implanted in the cranium. Infections related to neurostimulator procedures were assessed in patients treated with the RNS System. The types of infections, the rate over time and the rate with each neurostimulator related procedure are reported here. Methods: All infection related serious adverse events (SAEs) that were not due to a seizure and were adjudicated as device related or of uncertain device relation were identified for the patients in the RNS System trials. SAEs were defined as adverse events requiring a procedure or hospitalization. Rates were calculated as 1) chance of infection per neurostimulator procedure 2) incidence of infection per patient implant year, and 3) rates of infection for the initial implant and for each subsequent replacement (as of 11/01/2015). Infection and erosion rates as a function of the number of neurostimulator procedures were analyzed using the generalized estimating equation (GEE). A constant cohort analysis was also performed for those patients who had at least 4 procedures (McNemar's Test). Rates for patients with more than 4 procedures could not be confidently calculated due to the small number of patients in that group. Results: Patients implanted with the RNS Neurostimulator and Leads (n=265) were followed for an average of 6.9 years (10 days ?" 11 years). The first generation device had a median 2.2 year battery lifespan [1] and the current device is estimated to last 3.9 years [2]. Development of a next generation device with substantially increased battery life has been completed [3]. The rate of SAEs related to infection was 0.018 per implant year (31 events/ 1,715.2 years) and 3.69 % per neurostimulator procedure (n=31/840). The rate of infection did not increase with subsequent procedures (p=0.66, GEE), nor did the rate of erosion (p=0.70, GEE). Having had an infection or erosion at a prior procedure did not significantly increase the risk of having an infection or erosion at a later procedure (p?- 0.05 for all combinations, McNemar's Exact). Infections in all but one of the 28 patients were soft tissue; one patient developed osteomyelitis after a single procedure that included explant of the RNS System, subdural grid mapping, frontal lobe resection, and re-implantation of the RNS System. Culture results were available for 22/31 infections in patients. Agents included Staphylococcus (10), Propionibacterium (5), Serratia (2), Pseudomonas (3), and E. coli (1). 20 patients had the neurostimulator explanted. Four were subsequently re-implanted. [1] RNS-300 model, DN 1014918 Rev 2 ?" Manual, Clinical Summary p.48 [2] RNS-300M model, based on moderate use profile, DN 1015882 Rev 2 - User Manual p. 27 [3] Personal communication from NeuroPace, Inc. Conclusions: A cranial implant offers several advantages over a pectoral implant. The signal to noise ratio is excellent and the implant is not apparent to the patient and others, providing cosmetic advantage. These long-term data suggest that the rates of infection and erosion do not increase with subsequent neurostimulator replacement procedures and that most infections represent skin flora. The rate of implant related infections in the RNS System clinical trials compares favorably to rates with pectorally implanted pulse generators [4][5]. [4] Rate of serious infection in DBS trial for epilepsy = 10.0%. Salanova, V., et al, SANTE Study Group, 2015. Neurology 84, 1017?"1025 [5] Rate of superficial and deep infection for VNS = 5.0% per stimulator procedure. Kahlow H, Olivecrona M. Seizure 2013;22:827-833 Funding: None.