Treatment of Multi-Focal Epilepsy With Resective Surgery Plus Responsive Neurostimulation (RNS): One Institution's Experience.

ORIGINAL RESEARCH published: 29 October 2020 doi: 10.3389/fneur.2020.545074 Treatment of Multi-Focal Epilepsy With Resective Surgery Plus Responsive Neurostimulation (RNS): One Institution’s Experience Diem Kieu Tran 1*, Demi Chi Tran 2 , Lilit Mnatsakayan 2 , Jack Lin 2 , Frank Hsu 1 and Sumeet Vadera 1 1 Department of Neurological Surgery, University of California, Irvine, Irvine, CA, United States, 2 Department of Neurology, University of California, Irvine, Irvine, CA, United States Edited by: Jorge Alvaro Gonzalez-Martinez, University of Pittsburgh, United States Reviewed by: Carlo Di Bonaventura, Sapienza University of Rome, Italy Francesca Izzi, Policlinico Tor Vergata, Italy *Correspondence: Diem Kieu Tran Specialty section: This article was submitted to Epilepsy, a section of the journal Frontiers in Neurology Received: 23 March 2020 Accepted: 31 August 2020 Published: 29 October 2020 Citation: Tran DK, Tran DC, Mnatsakayan L, Lin J, Hsu F and Vadera S (2020) Treatment of Multi-Focal Epilepsy With Resective Surgery Plus Responsive Neurostimulation (RNS): One Institution’s Experience. Front. Neurol. 11:545074. doi: 10.3389/fneur.2020.545074 Frontiers in Neurology | www.frontiersin.org Objective: Patients with medically refractory focal epilepsy can be difficult to treat surgically, especially if invasive monitoring reveals multiple ictal onset zones. Possible therapeutic options may include resection, neurostimulation, laser ablation, or a combination of these surgical modalities. To date, no study has examined outcomes associated with resection plus responsive neurostimulation (RNS, Neuropace, Inc., Mountain View, CA) implantation and we describe our initial experience in patients with multifocal epilepsy undergoing this combination therapy. Methods: A total of 43 responsive neurostimulation (RNS) devices were implanted at UCI from 2015 to 2019. We retrospectively reviewed charts of patients from the same time period who underwent both resection and RNS implantation. Patients were required to have independent or multifocal onset, undergo resection and RNS implantation, and have a minimum of six-months for follow-up to be included in the study. Demographics, location of ictal onset, location of surgery, complications, and seizure outcome were collected. Results: Ten patients met inclusion criteria for the study, and seven underwent both procedures in the same setting. The average age was 36. All patients had multifocal ictal onset on video electroencephalogram or invasive EEG with four patients undergoing subdural grid placement and four patients undergoing bilateral sEEG prior to the definitive surgery. Five patients underwent resection plus ipsilateral RNS placement and the remainder underwent resection with contralateral RNS placement. Two minor complications were encountered in this group. At six months follow up, there was an average of 81% ± 9 reduction in seizures, while four patients experienced complete seizure freedom at 1 year. Conclusion: Patients with multifocal epilepsy can be treated with partial resection plus RNS. The complication rates are low with potential for worthwhile seizure reduction. Keywords: epilepsy, lobectomy, temporal, surgery, robotic, responsive neurostimulation (RNS) 1 October 2020 | Volume 11 | Article 545074 Tran et al. Treatment of Multi-Focal Epilepsy INTRODUCTION areas. This combination approach provides the ability to expand the treatment area outside of what is possible with resection alone. The authors demonstrate their early series of patients who underwent resection and RNS as part of their surgical management. Approximately one-third of epilepsy patients have seizures that are refractory to antiepileptic medications (1, 2). Left untreated, patients are at risk of developing multiple comorbidities, and potentially death (3). For this reason, patients with medically refractory focal epilepsy should be referred to a Level 4 NAEC (National Association of Epilepsy Centers) center to be evaluated for surgical candidacy. The best outcomes are seen with temporal lobectomy for mesial temporal sclerosis (MTS) or other lesional resections, with 68% of patients with MTS becoming seizure free and 50% of neocortical extratemporal resections becoming seizure free at 2 years (4). After being diagnosed with medically refractory epilepsy, pre-surgical evaluation includes video electroencephalography (EEG) monitoring to localize the ictal onset zone(s). If ictal onset is difficult to localize, or if bilateral or eloquent area ictal onset is suspected, the patients move on to have invasive monitoring studies including stereoelectroencephalography (sEEG) or subdural grids (SDG) to better delineate the ictal onset zone(s). Depending upon the location of the onset zone, subsequent resection, neurostimulation, or laser ablation might be performed. However, there are limitations associated with performing resections including the inability to perform bilateral resection of the same lobe and the unfavorable functional outcomes associated with resecting eloquent regions. Therefore, patients with medically refractory epilepsy which involve multiple independent ictal onset zones or eloquent areas can be very difficult to treat surgically. Historically, when there is bilateral or multifocal ictal onset, palliative procedures such as callosotomy or neuromodulation have been performed (5–9). Unfortunately, these rarely result in complete seizure freedom. The authors describe their experience with resection of primary ictal onset zone as well as RNS implantation for additional ictal onset METHODS Patient Selection A total of 43 responsive neurostimulation (RNS) were placed at UCI from 2013 to 2019. To be included in the study, patients must have independent multifocal ictal onset which was demonstrated with video encephalography (vEEG) or invasive monitoring (sEEG or SDG) and undergone resection plus RNS implantation. Resection and RNS implantation were not required to be performed during the same surgical setting. Subjects must also have at least six months of follow up. Between February 2015 to January 2019, 10 patients met inclusion criteria and underwent responsive neurostimulation implantation as well as a resective procedure. Eight out of ten patients underwent phase two invasive monitoring with either SDG placement and sEEG or bilateral sEEG, while two patients underwent definitive treatment without undergoing invasive monitoring (Tables 1, 2). This study was approved by the University of California, Irvine’s Institutional Review Board (IRB). Presurgical Workup All patients completed neuroimaging, neuropsychological testing, and non-invasive vEEG as part of their phase one evaluation. They were then presented and discussed at our institution’s multidisciplinary epilepsy management conference. Epileptologists, neuroradiologists, and neuropsychologists as well as the senior author (SV) were present during these conferences. The (...truncated)