Chronic recording electrocorticography guided resective epilepsy surgery: overview and future directions

Transcription

1 Molecular & Cellular Epilepsy 2014; 1: e RESEARCH HIGHLIGHT Chronic recording electrocorticography guided resective epilepsy surgery: overview and future directions Daniel J. DiLorenzo 1, Erwin Z. Mangubat 1, Marvin A. Rossi 2, Richard W. Byrne 1, 1 Department of Neurosurgery, Rush University Medical Center, Chicago, IL 2 Department of Neurology, Rush University Medical Center, Chicago, IL Correspondence: Daniel J. DiLorenzo djdilore@alum.mit.edu Received: June 18, 2014 Published online: November 07, 2014 Sensing, modeling, and neuromodulation technologies are profoundly advancing the practice of epilepsy surgery. Chronically implanted neural monitoring technologies developed for seizure termination and seizure prediction have each been found to be useful in unintended applications, specifically for the planning of resective surgery. We review and summarize the use of chronic monitoring in an unanticipated context in which it was found to be invaluable in the planning of surgery; this was observed in a pivotal study of a seizure detection and termination system. Monitoring of patients chronically in their normal ambulatory setting, as facilitated by this technology, allows unperturbed assessment of patients while on outpatient medication regimens and without the time and space constraints imposed by cost and infection risk inherent in subacute inpatient invasive monitoring. Five patients in the NeuroPace US pivotal trial underwent resective surgery which was subsequent to and enabled by chronic recordings from the implanted monitoring system. These resective surgeries were independent from the primary intended function of the implanted neural monitoring device. Chronic monitoring facilitated greater anatomical localization of the sources and allowed for a deeper understanding of the dynamic network behavior of interconnected seizure foci, thereby facilitating a substantially more sophisticated approach to resective surgery. In the NeuroPace trial, monitoring and analysis of chronic unlimited recording electrocorticography (CURE) from chronically implanted subdural and depth electrodes facilitated planning of resective surgery that resulted in near or complete seizure freedom in 4 patients. This series suggests that chronic recording of electrocorticographic signals is a therapeutic modality meritorious of further investigation. Keywords: intracranial monitoring; subdural electrodes; intracranial electrodes; seizure focus localization; chronic monitoring; epilepsy surgery; electrocorticography; ECoG Molecular & Cellular Epilepsy 2014; 1: e208. doi: /mce.208; 2014 by Daniel J. DiLorenzo. Introduction Acceptance of irreversible resective epilepsy surgery as a therapeutic modality is generally met with trepidation by patients and only offered by surgeons when the likely benefits exceed the risks. In appropriately selected patients and with sufficiently localized sources and characterized networks, resection offers a high probability of achieving seizure freedom. Clinical workflow with noninvasive anatomical and functional imaging has undergone substantial advancement in the past decade due to both technological progress and to integration of existing technologies into clinical practice. Refinements in MRI, functional MRI (fmri), positron emission tomography (PET), single-photon emission computed tomography (SPECT), subtraction ictal SPECT co-registered to MRI (SISCOM), magnetoencephalography (MEG), and stimulation 1

2 Figure 1. Post-Implantation Pre-Resection Imaging demonstrating chronic recording electrode configurations. Left column images ( i ): Lateral Scout / X-Ray images of patients with chronic monitoring system implanted prior to GURE-guided resective surgery, demonstrating position of implanted recording electrodes. Right column images ( ii ): Axial CT images status post CURE-guided resection. Fig 1A: patient 1. Fig 1B: patient 2. Fig 1C: patient 3. Fig 1D: patient 4. activated SPECT (SAS) continue to improve sensitivity in source detection, accuracy in source localization, and sophistication in network characterization [2, 3]. Nonetheless, a small portion of patients (approximately 12% in our institution) remain insufficiently characterized and do not progress to definitive surgery. The majority of these patients endure [1] progressive worsening of their seizure symptomatology (unpublished data). A new technique, reported independently by two groups, offers promise to this group of patients. Initial and separate reports using two novel chronically implanted neural monitoring technologies, the Responsive Neurostimulator (RNS) developed by NeuroPace [4-6] and the Seizure Advisory System (SAS) developed by NeuroVista, [7-9] have shown initial promise in 5 patients using a new modality of pre-resective identification of the ictal source and circuit. Herein, we summarize our findings in which we utilized chronic recording electrocorticography to plan resective epilepsy surgery and achieve seizure freedom in 4 patients implanted with the NeuroPace system [10]. As part of the multi-center pivotal study for the NeuroPace Responsive Neurostimulation (RNS) System [4], 11 of the 191 patients implanted were treated at Rush. Separate and distinct from the seizure detection and neuromodulatory functions of the device, we analyzed chronically recorded signals to better localize epileptic sources and the dynamics of the seizure network. In 4 patients, a high degree of confidence was gained that further resection could provide improvement in seizure control. In a 5 th patient, with multiple sources in a double band heterotopia, resection was offered and pursued as a palliative option. As part of the First in Man (FIM) study conducted for the NeuroVista Seizure Advisory System (SAS), 15 patients were implanted at 3 centers in Australia. In one of these patients, a previously unidentified seizure source was localized and successfully resected using the chronically recorded signals from the implanted SAS device. Unmet Clinical Need: Approximately 40% of patients with epilepsy remain refractory to medical therapy and are potential candidates for resective or neuromodulatory surgical therapy. Noninvasive pre-surgical evaluation, when anatomically definitive, concordant, and suggestive of non-eloquent regions, is generally sufficient for planning of resective surgery. In approximately 25% of these patients, noninvasive workup is insufficient; and invasive monitoring is required [11] [12]. As reported in the late 1930 s by Penfield [13], monitoring of electrocorticographic (ECoG) signals from subacutely implanted subdural cortical and depth electrodes offers higher spatial resolution and frequency characteristics than that provided by scalp EEG [14] [15] [16] Infection risk limits this modality to typical durations of 5-10 days and maximal durations of 2-4 weeks, severely restricting the potential to record seizures, particularly if infrequent [17]. Cessation of antiepileptic (AED) medications is often required to induce seizures within this time window [18]. In a subset of patients who undergo subacute invasive 2

3 monitoring, estimated to be 12% in an unpublished series at Rush, the recorded data is not sufficient for localization and surgical planning; and these patients do not progress to surgery and endure progressively worsening seizures and declining quality of life. An additional subset progress to but do not achieve seizure freedom. Chronic recording electrocorticography offers promise to both of these subsets of patients. Methods Among the 191 patients implanted in the NeuroPace RNS Pivotal trial [4], 11 were implanted at Rush [5] University. The RNS technology and surgical [19] implantation technique have been described previously. The inclusion criteria for the NeuroPace RNS System pivotal trial were. (1) Disabling motor simple partial seizures, complex partial seizures, or secondarily generalized seizures, (2) failed treatment with a minimum of two anti-seizure medications, (3) an average of three or more seizures every 28 days for three consecutive 28-day periods, (4) between the ages of 18 and 70 years, (5) no more than two epileptogenic regions [10] [20]. Based upon work by Rossi et al., the temporal depth electrodes were placed in peri-hippocampal white matter to facilitate interfacing with tracts believed to comprise part of the ictal circuit and therefore facilitate seizure generation or propagation [1]. As reported by DiLorenzo, Mangubat, Rossi, and Byrne in 2014, entirely separate from the RNS therapeutic aspect of this study, electrocorticographic signals were monitored and analyzed. In four of these 11 patients, presented herein, analysis of these recordings facilitated better characterization of at least one of the ictal source and the ictal circuit [10]. The protocol described herein and the multi-center RNS System Pivotal Clinical Trial were approved by the RUMC Institutional Review Board. All patients voluntarily enrolled in this study. Results The four patients from the NeuroPace pivotal study at Rush who underwent chronic recording electrocorticography-guided therapeutic resection are described below, and the cases are summarized in Table 1. Patient 1 (TS) is a 26 year old right handed female, who was found to have a right temporal astrocytoma at age 13 months, underwent resection x3, subsequently developed seizures at age 13 with semiology comprising staring spells with an alteration in awareness as well as independent prolonged episodes of nausea and vomiting. At age 17, she was diagnosed with epilepsy and was implanted with a VNS system with no improvement. Because of bilateral temporal involvement compounded by aversion to surgery due to left hemiparesis from the previous resections, further resection was not pursued, and she was implanted with an RNS system. She was a responder and realized greater than 50% reduction in the staring spell seizure type with persistence in the nausea and vomiting episodes. The patient and family voiced a strong desire for further improvement in seizure control, particularly the episodes of nausea and vomiting. Chronic recording electrocorticography suggested coupling of the bitemporal circuits and pre-rns workup correlated left temporal and insula activity with these nausea and vomiting episodes; therefore, a right sided completion temporal lobectomy was pursued to eliminate the problematic seizures and interrupt the bitemporal coupling to potentially further reduce or eliminate the contralateral seizures. Post-resection, the patient has been seizure free with the exception of one seizure with tapering of propofol after a GI procedure. She has otherwise been seizure free for 42 months [10]. Patient 2 (CH) is a 29 year old right handed male who had his first seizure at age 17 after being stung by a jellyfish, subsequently developed complex partial and secondarily generalized tonic-clonic seizures. Two years later, he was struck in the left side of the head with a shot-put at a track meet, sustaining traumatic brain injury with a contusion and worsening of his complex partial seizures, which were characterized by an aura in which he feels weird followed by silence and automatisms in the form of staring, smiling, chewing movements, speech arrest, drooling, and coughing, followed by head turning. His bilateral temporal involvement rendered him a poor surgical candidate, and he was implanted with the RNS system, from which he derived improvement in the right temporal seizures and poor control of the left temporal seizures, realizing an approximate 50% reduction in total clinical seizures. Chronic recording electrocorticography monitoring demonstrated persisting uncontrolled clinical and electrographic seizures arising from a left temporal focus and control of the right temporal region with the RNS System, supporting the therapeutic benefit of left temporal resective surgery. A left temporal corticectomy, involving the removal solely of scarred avascular brain, was performed; and the left lateral temporal subdural electrode was repositioned behind the line of resection and sutured to the dura. Following this resection, he has been seizure free for 23 months (1.9 years) [10]. Patient 3 is a 45 year old male, with multiple seizure type beginning at age 14, initially presenting as complex partial seizures and which at age 27, were supplanted by simple partial seizures in the form of a reflex epilepsy characterized by sudden loss of muscle tone and falls triggered by somatosensory stimulation of his left foot, 3

4 such as walking on uneven or textured surfaces, not accompanied by loss of consciousness but occasionally resulting in secondary generalized tonic-clonic seizures. A VNS system was implanted at age 33, provided minimal benefit, and was removed. Because of the eloquent location of his focus in somatosensory area, resective surgery was not recommended or pursued, and he underwent RNS implantation at age 37 with strip electrodes in the interhemispheric fissure and right superior frontal gyrus with subsequent revision to a depth electrode in the right superior frontal gyrus. His seizures with falling persisted, chronic recordings provided greater anatomical localization of the source, and he underwent CURE guided resective surgery at age 42 and has remained seizure free since then for 41 months [10]. Patient 4 (RK) is a 42 year old right handed male with a history of seizure disorder since age 8, beginning as seeing colors in his right visual field followed by loss of vision on that side. At age 24, he received a VNS system as part of the VNS pivotal trial, derived no significant improvement, and has the device removed after 9 months. He subsequently underwent three resective procedures, including left occipital multiple subpial transections at age 28, left occipital cortical focus resection and subpial transection, and further resection at age 34, each with at best only transient improvement followed by persistence of seizures, suggesting presence of dual pathology. Because of the concern for sources in two eloquent regions (left occipital and temporal), further resection was not pursued; and at age 34, he underwent left occipital craniotomy with implantation of an RNS with a subdural electrode strip in the interhemispheric fissure in contact with the left mesial occipital region and a depth electrode in the temporal lobe white matter parallel to the hippocampus. The RNS failed to provide substantive benefit, after only a transient initial improvement for several months; and the RNS was removed 22 months later. Chronic recording electrocorticography signals were consistent with a single occipital source, and he subsequently underwent resective surgery comprising an occipital disconnection procedure at age 36. He has one post-operative seizure during a medication taper and has remained seizure free since then for 69 months [10]. Discussion In each of these 4 cases, prior to chronic intracranial monitoring, anatomical localization or ictal circuit characterization was insufficient to justify progression to resective surgery. In this small set of 4 patients from two separate studies using different intracranial systems, chronic intracranial monitoring facilitated refinement of source localization beyond that realized with available noninvasive and in-hospital intracranial recordings. This chronic data provided the treating neurologists and neurosurgeons with sufficient additional information for anatomical localization or characterization of the ictal circuit such that a satisfactory probability of a curative outcome justified progression with resective surgery. In each of these 4 cases, pre-cure guided surgery quality of life was severely compromised by frequent and refractory seizures; and following surgery, a prolonged seizure-free state was achieved. These 4 cases represent the use of state of the art technology and workflow in the workup and treatment of medically refractory seizures in a major tertiary center and in each, the use of chronic recording electrocorticography monitoring facilitated further characterization of the ictal circuits and dynamics thereof to facilitate safe and efficacious resective surgery. Prolonged seizure-free states were thereby achieved in patients with previously refractory seizures. This review and update demonstrates the experience using one implantable devices (NeuroPace RNS) in a pivotal study. Comparable use of a truly continuous recording system have been noted using the NeuroVista Seizure Advisory System [7]. The utilization of systems in the context of these studies was done in the course of their intended uses and in subsequent clinical care; however, this chronic recording electrocorticography modality alone could potentially be considered as an off label use of the respective technologies. Some subtle differences in these systems is worthy of mention. The RNS System has a limited data storage capability of 6 minutes and records a series of distinct and finite time epochs (typically four 90 second epochs) rather than continuous data; therefore, these ECoG recordings are not truly unlimited but are in fact intermittent. The NeuroVista Seizure Advisory System SAS (acquired by Cyberonics) provides recordings which are continuous in time and which possess simultaneous auditory data, which is useful in confirming clinical seizure activity. Other chronically implanted monitoring systems under development by other groups, and these may also be found to provide comparable utility. Conclusion In the majority of patients referred for surgical treatment, noninvasive and subacute invasive monitoring is able to provide sufficient source and circuit characterization to facilitate resective surgery. A portion of these patents, approximately 10-15%, do not progress to surgery because of insufficient characterization. In this population of patients, chronic monitoring, as described herein and in our initial report [10], may provide 4

5 another opportunity for definitive resective surgery and chance for seizure freedom. We summarize the 4 first cases reported in detail to date in which fully implanted chronic ambulatory recording systems offer the potential to advance the clinical practice in resective epilepsy surgery and thereby expand the potential set of patients who may realize seizure freedom. Conflicting interests The Responsive Neurostimulation (RNS ) System was provided by NeuroPace as part of their pivotal trial. No further support was required for this study. The Seizure Advisory System (SAS ) was provided by NeuroVista (acquired by Cyberonics ) as part of their first In Man trial. One author DJD is the founder of NeuroVista (acquired by Cyberonics ) and has an ownership interest in some intellectual property relating to chronic neural monitoring and to closed-loop neuromodulation. References 1. Rossi, M.A., G. Stebbins, C. Murphy, D. Greene, S. Brinker, D. Sarcu, et al. Predicting white matter targets for direct neurostimulation therapy. Epilepsy Res 2010; 91: So, E.L. Integration of EEG, MRI, and SPECT in Localizing the Seizure Focus for Epilepsy Surgery. Epilepsia 2000; 41: S48-S Ahnlide, J.-A., I. Rosén, P. Lindén-Mickelsson Tech, K. Källén. Does SISCOM Contribute to Favorable Seizure Outcome after Epilepsy Surgery? Epilepsia 2007; 48: Morrell, M.J., for the RNS System in Epilepsy Study Group. Responsive cortical stimulation for the treatment of medically intractable partial epilepsy. Neurology 2011; 77: Tcheng, T.K., M.J. Morrell. Responsive Neurostimulation for Epilepsy: RNS Technology and Clinical Studies, In Neuroengineering. Edited by D.J. DiLorenzo and J.D. Bronzino. Boca Raton, FL: CRC Press / Taylor and Francis Books; 2007: 5-1 to Fischell, R.E., D.R. Fischell, A.R.M. Upton, System for treatment of neurological disorders, Filed: Oct. 27, 1997, A/N: Issued: Jan. 18, 2000, Pat #: 6,016, Cook, M.J., T.J. O'Brien, S.F. Berkovic, M. Murphy, A. Morokoff, G. Fabinyi, et al. Prediction of seizure likelihood with a long-term, implanted seizure advisory system in patients with drug-resistant epilepsy: a first-in-man study. Lancet Neurol 2013; 12: Fisher, R.S. Therapeutic devices for epilepsy. Ann Neurol 2012; 71: DiLorenzo, D.J., Apparatus and method for closed-loop intracranial stimulation for optimal control of neurological disease, Filed: June 25, 1999, A/N: US 09/340,326, Issued: April 2, 2002, Pat #: 6,366, DiLorenzo, D.J., E.Z. Mangubat, M.A. Rossi, R.W. Byrne. Chronic unlimited recording electrocorticography - guided resective epilepsy surgery: technology-enabled enhanced fidelity in seizure focus localization with improved surgical efficacy. Journal of Neurosurgery 2014; 120: Spencer, S.S., P. Guimaraes, A. Shewmon. Intracranial electrodes, In Epilepsy: a comprehensive textbook. Edited by J. Engel Jr and T.A. Pedley. New York, NY: Lippincott Raven; 1998: Nair, D.R., R. Burgess, C.C. McIntyre, H. Luders. Chronic subdural electrodes in the management of epilepsy. Clin Neurophysiol 2008; 119: Morris, H.H., 3rd, H. Luders. Electrodes. Electroencephalogr Clin Neurophysiol Suppl 1985; 37: Luders, H., I. Awad, R. Burgess, E. Wyllie, P. Van Ness. Subdural electrodes in the presurgical evaluation for surgery of epilepsy. Epilepsy Res Suppl 1992; 5: Wyllie, E., H. Luders, H.H. Morris, 3rd, R.P. Lesser, D.S. Dinner, A.D. Rothner, et al. Subdural electrodes in the evaluation for epilepsy surgery in children and adults. Neuropediatrics 1988; 19: Tao, J.X., A. Ray, S. Hawes-Ebersole, J.S. Ebersole. Intracranial EEG substrates of scalp EEG interictal spikes. Epilepsia 2005; 46: Lesser, R.P., N.E. Crone, W.R. Webber. Using subdural electrodes to assess the safety of resections. Epilepsy Behav 2011; 20: Swick, C.T., A. Bouthillier, S.S. Spencer. Seizure occurrence during long-term monitoring. Epilepsia 1996; 37: Fountas, K.N., J.R. Smith. Responsive Neurostimulation for Epilepsy Neurosurgical Experience: Patient Selection and Implantation Technique, In Neuroengineering. Edited by D.J. DiLorenzo and J.D. Bronzino. Boca Raton, FL: CRC Press / Taylor and Francis Books; 2007: 5-1 to NeuroPace, Responsive Neurostimulator (RNS) System Pivotal - A Clinical Investigation Plan p To cite this article: Daniel J. DiLorenzo, et al. Chronic recording electrocorticography guided resective epilepsy surgery: overview and future directions. Mol Cell Epilepsy 2014; 1: e208. doi: /mce

6 Supplementary Files Table 1. Summary of Patient Characteristics, Management, and Outcome. Demographics, neuropathologic features, seizure etiology and semiology, reason for nonsurgical management, chronic recording electrocorticography modalities (electrodes and locations), RNS effects, chronic recording electrocorticography insights pre-resection, resective surgical interventions, and results are presented for each of the 4 patients presented in this review. 6