CHRONIC IMPLANTATION OF THE RESPONSIVE NEUROSTIMULATOR (RNS) LEAD SYSTEM IN THE SHEEP MODEL TO DEMONSTRATE ESSENTIAL SAFETY PRIOR TO A HUMAN CLINICAL TRIAL
December 2002
Abstract presented at the Annual Meeting of the American Epilepsy Society
Robert Sweazey, Michael Munz, Harry Vinters, Carla Barrett, Audra Plenys, David Greene.
RATIONALE: The RNS Lead System consists of quadripolar depth and cortical strip leads and are a component of the NeuroPace RNS System, which is intended for chronic implantation as a therapy for intractable epilepsy. The objective of this study is to demonstrate the essential safety of the lead system through chronic implantation and stimulation in the sheep model.
METHODS: Using a protocol approved by the Purdue Animal Use and Care Committee and consistent with FDA and USDA guidelines, a consecutive series of eight male, wethered suffolk sheep (age 5 to 16 months) were bilaterally implanted with strip and depth leads (four leads per animal). Sedation with Xylazine and Sodium Pentothal, followed by intubation and Isoflurane maintenance anesthesia were utilized. Hippocampal depth lead placements were performed stereotactically 5 mm anterior to the interaural canal with the head in a 15-degree down angle. Coordinates were determined via a sheep brain atlas in conjunction with MRI scans performed following two initial feasibility procedures. Lead introduction was made through 14mm burr holes. Sub-dural cortical strip lead placements were performed in the same burr holes with the leads advanced rostrally and located over the parietal and frontal lobes. Leads were stabilized with burr hole covers. To assess the differential neural response resulting from stimulation, one side (consisting of a depth and strip lead) was externalized for periodic electrical stimulation whereas the other side were totally implanted and were not stimulated. Lead position was documented via dual plane x-rays. Post-operative analgesia using IM Torbugesic was administered for 3 days and the animals were allowed to recover for 7 days. The externalized leads received 30 minutes of continuous stimulation per lead each week (50 Hz, 2.5 mA, 300 µs phase duration, biphasic) and weekly impedance measurements and signal recordings were performed. After survival periods ranging from 6-9 months, the brains will undergo histopatological examination at the UCLA Medical Center using multiple staining techniques (hematoxylin and eosin, Kluver-Barrera, glial fibrillary acidic protein, and a microglial marker).
RESULTS: Implantations began in December 2001 and will be completed in May 2002. Initial results (survival to 5 months) show stable impedance and ECOG recordings. Preliminary histopathological data from an animal survived 2 months showed expected reactions consistent with published results for DBS leads. The results from the full series including histopathological examination will be presented.
CONCLUSIONS: The RNS represents a novel approach for the treatment of epilepsy. This study is an important part of the pre-clinical work required to begin the clinical trial of the system in patients.
 Return to Top | Return to Publications
|
