Abstract BACKGROUND Responsive neurostimulation (RNS) is a relatively new treatment option that has been shown to be effective for patients with medically refractory focal epilepsy when resection is not possible, especially in bilateral mesial temporal onset. Robotic devices are becoming increasingly popular for use in stereotactic procedures such as stereoelectroencephalography, but have yet to be used when implanting RNS devices. OBJECTIVE To show that these 2 forms of advanced technology were compatible and could be used effectively in patient care. METHODS We implanted RNS devices in 3 patients with bilateral mesial temporal lobe epilepsy. Each patient was placed in the prone position, and electrode trajectories were planned via the robotic navigation system via a transoccipital approach. One lead was placed along each amygdalohippocampal complex. A small craniectomy was then created in the parietal region for RNS generator implantation. Actual and expected target locations and distance were calculated for each depth. There were no complications in this group. RESULTS RNS devices with bilateral leads were successfully implanted in all 3 patients, with bilateral mesial temporal lobe onset. Follow-up ranged from 3 to 6 mo, and there were no complications in this group. The median distance between the estimate and actual targets was 2.18 (range = 1.11-3.27) mm. CONCLUSION We show that implanting RNS devices with robotic assistance is feasible with excellent precision and accuracy. The advantages of using robotic assistance include higher flexibility, accuracy, precision, and consistency. RNS system, ROSA robot, Closed loop system ABBREVIATIONS ABBREVIATIONS CT computed tomography DBS deep brain stimulation ECoG electrocorticography MRI magnetic resonance imaging RNS responsive neurostimulation SEEG stereoelectroencephalography vEEG video electroencephalography VNS vagus nerve stimulator Responsive neurostimulation (RNS) is a good option to treat medically refractory focal epilepsy in patients who are not good candidates for resection, such as when ictal onset is close to functional tissue or in the setting of 2 distinct foci (eg, bilateral mesial temporal lobe epilepsy). Forming a closed-loop stimulation system (ie, responsive via feedback), paddle or depth electrodes are implanted in the vicinity of the ictal onset zone and seizures are suppressed by electrically stimulating the epileptogenic focus when epileptiform activity is detected.1 RNS implantation is most commonly performed after localization of the ictal onset zone with invasive monitoring using subdural grids or stereoelectroencephalography (SEEG). RNS has been shown to be an excellent option in patients with bilateral mesial temporal lobe epilepsy.2,3 The use of robotic assistance in stereotactic procedures has become more popular recently. Robotic assistance has been used in a variety of procedures, including deep brain stimulation (DBS),4 laser ablation,5,6 and SEEG,7 and has proven to be an effective tool that excels with spatial information, allowing for accurate and precise placement of electrodes.5 Robot assistance also allows for creation of trajectories that are difficult with frame-based systems and also removes the risks of human error associated with calculations and trajectory planning.7 This report describes the first use of the ROSA stereotactic robot to implant bilateral RNS depth electrodes. Three patients with medically refractory focal epilepsy initially underwent SEEG implantation and were found to have seizures arising from both mesial temporal lobe structures. Subsequently, these patients underwent implantation of bilateral hippocampal leads and central RNS placement with stereotactic robotic guidance using a transoccipital approach to the amygdalohippocampal complex. This is the first described use of robotic assistance to RNS implantation and offers a novel technique for lead implantation for epilepsy surgeons utilizing RNS. METHODS RNS Device (RNS System) The RNS system (NeuroPace, Inc, Mountain View, California) was used in this study. The device was small impulse generator that was implanted via craniectomy into the parietal region of the skull and connected to 2 electrodes, which allowed it to detect epileptiform activity and stimulate the foci when appropriate. Both real-time and stored electrocorticography (ECoG) readings were obtained. Presurgical Workup Three patients with medically refractory focal epilepsy were discussed in Epilepsy Management Conference for possible RNS system placement. All patients underwent inpatient video electroencephalography (vEEG), proton emission tomography, and high-resolution magnetic resonance imaging (MRI); the patients then underwent SEEG depth electrode placement for epileptogenic foci localization (Table 1). Robotic assistance was also used in placing SEEG depth electrodes, which has been standard at our hospital since January 2015. One surgeon (SV) placed all SEEG depth electrodes in all the patients. Bilateral mesial temporal ictal onsets were confirmed in all patients and RNS was offered as primary treatment option. TABLE 1. Result Summary for the Patients Patient Epilepsy onset Age at procedure Refractory AEDs vEEG findings SEEG findings Preoperative MRI Surgical time Complic-ations Seizure frequency reduction at last follow-up 1 32 yr 34 yr Lamotrigine; lacosamide 9 seizures captured; 1 bilateral onset and 8 left temporal onset Bilateral mesial temporal lobe epileptogenic foci No abnormalities 147 min None 50% 2 3 yr 22 yr Valproic acid; carbamazepine; levetiracetam; lamotrigine; zonisamide; topiramate; felbamate; clonazepam 7 seizures captured; right and left hemispheric onset following a prolonged period of background attenuation (right more often than left) Bilateral mesial temporal lobe epileptogenic foci No abnormalities 134 min None 80% 3 21 yr 31 yr Topiramate; levetiracetam; carbamazepine 5 seizures in right middle temporal region; 4 seizures left anterior temporal Bilateral mesial temporal lobe epileptogenic foci Focal gloisis in left lateral temporal gyrus and right mesial temporal sclerosis 165 min None 100% Patient Epilepsy onset Age at procedure Refractory AEDs vEEG findings SEEG findings Preoperative MRI Surgical time Complic-ations Seizure frequency reduction at last follow-up 1 32 yr 34 yr Lamotrigine; lacosamide 9 seizures captured; 1 bilateral onset and 8 left temporal onset Bilateral mesial temporal lobe epileptogenic foci No abnormalities 147 min None 50% 2 3 yr 22 yr Valproic acid; carbamazepine; levetiracetam; lamotrigine; zonisamide; topiramate; felbamate; clonazepam 7 seizures captured; right and left hemispheric onset following a prolonged period of background attenuation (right more often than left) Bilateral mesial temporal lobe epileptogenic foci No abnormalities 134 min None 80% 3 21 yr 31 yr Topiramate; levetiracetam; carbamazepine 5 seizures in right middle temporal region; 4 seizures left anterior temporal Bilateral mesial temporal lobe epileptogenic foci Focal gloisis in left lateral temporal gyrus and right mesial temporal sclerosis 165 min None 100% View Large Procedure Each patient was brought into the operating room and given anesthesia for induction of general anesthesia. The patient was then placed in a Leksell stereotactic head frame (Elekta, Crawley, United Kingdom) and placed in a prone position. The Leksell head frame was not used for stereotactic navigational purposes—rather, it only connected the robot to the patient. We fixed skull fiducials to the patient and then performed intraoperative computed tomography (CT) scan prior to stereotactically registering the patient to the robotic navigation system. Each patient was registered to the robot with the robot's pointer probes and the skull fiducials. The images from the CT were loaded to the robot, where the preoperative MRI and CT were also fused. Upon completion, the surgeon (SV) used the robot to plan 2 appropriate trajectories and distance to the targets through the mesial temporal lobes (Figure 1). FIGURE 1. View largeDownload slide Imaging of a representative patient with RNS implant. Panel A, image of trajectory through the temporal lobe; panel B, radiograph of patient skull with RNS device. FIGURE 1. View largeDownload slide Imaging of a representative patient with RNS implant. Panel A, image of trajectory through the temporal lobe; panel B, radiograph of patient skull with RNS device. Specifically, the robots created the trajectory and the robotic arm was positioned properly. A small incision at the electrode insertion site was then made bilaterally in the occipital region. A 3 mm probe was used to access the cranial vault. A dural probe was used to make a small opening in the dura. A stylet was marked to the appropriate length and placed through the robot arm, creating an intracranial tract. The depth electrode was then placed through the robotic arm and affixed to the bone edge with a small plastic sheath. The robotic arm was used to maintain the trajectory and guide the placement of 2 RNS neurostimulator leads within the mesial temporal lobe bilaterally (see Figure 2 for images). A craniectomy in the shape of the RNS generator was created in the parietal region and the RNS generator was then placed and connected to the leads. The left lead was placed into the “1 position” on the generator and the right lead was placed into the “2 position.” Then, intraoperative testing was performed along with programming. The device was set to “off.” All impedances were within the expected range. A second CT scan showed that the placement was adequate. There were no immediate complications. FIGURE 2. View largeDownload slide Intraoperative photos taken of the surgery. Panel A, image of patient preparation; panel B, image of robot; panel C, image of operation; panel D, image of RNS generator in place. FIGURE 2. View largeDownload slide Intraoperative photos taken of the surgery. Panel A, image of patient preparation; panel B, image of robot; panel C, image of operation; panel D, image of RNS generator in place. Accuracy Data Calculation We uploaded the postoperative thin-cut CT to the ROSA software and calculated actual vs expected target location for each electrode for the right and left electrode for each patient. After picking midline points (AC, PC, interhemispheric point) to orient the robotic software, the software calculated expected target and actual target 3-D coordinates. We then calculated the difference between expected and actual targets in 3-dimension. We also were able to measure the straight linear distance between actual and expected targets. Data Collection We reviewed all the charts retrospectively. The data relevant to technique involving electrode insertion, device implantation, complications, length of surgery, and EcOG data (Figure 3) were collected. The Institutional Review Board at our university has approved the study of these patients. All patients consented to the surgery. FIGURE 3. View largeDownload slide Sample ECoG data obtained from 1 patient showing ictal onset, which correspond to the body of the right hippocampus. FIGURE 3. View largeDownload slide Sample ECoG data obtained from 1 patient showing ictal onset, which correspond to the body of the right hippocampus. For accuracy data, we collected coordinate data of the estimated targets, the actual targets, and the direct linear distances between them for each of the 2 electrodes implanted in our 3 patients. RESULTS The patient results are summarized in Table 1. Seizures in all 3 patients were bilateral and unresponsive to multiple antiepileptic drugs. There were no immediate or unexpected complications postoperatively at 6 mo of surgery for all patients. There was a reduction in seizure frequency for all 3 patients. The results for the accuracy of electrode implantation via robotic assistance are summarized in Table 2. The median distance between the estimate and actual targets was 2.18 (range = 1.11-3.27) mm (see Figure 4). FIGURE 4. View largeDownload slide Example of direct linear distance between estimated and actual targets calculated by the robot. FIGURE 4. View largeDownload slide Example of direct linear distance between estimated and actual targets calculated by the robot. TABLE 2. Summary of Accuracy Results Patient Electrode Expected/actual X-coordinate (mm) Y-coordinate (mm) Z-coordinate (mm) Linear distance (mm) 1 Left Expected –18.07 2.09 –19.14 3.21 Actual –19.90 –1.17 –21.84 Right Expected 17.60 2.09 –16.73 2.53 Actual 17.73 3.46 –18.69 2 Left Expected –18.30 21.63 –15.43 1.71 Actual –19.77 22.18 –16.69 Right Expected 22.53 26.24 –18.79 1.82 Actual 22.58 25.65 –20.60 3 Left Expected –16.45 –1.38 –17.84 1.11 Actual –16.08 –0.43 –18.00 Right Expected 17.08 1.84 –13.24 3.27 Actual 17.69 –1.38 –15.84 Patient Electrode Expected/actual X-coordinate (mm) Y-coordinate (mm) Z-coordinate (mm) Linear distance (mm) 1 Left Expected –18.07 2.09 –19.14 3.21 Actual –19.90 –1.17 –21.84 Right Expected 17.60 2.09 –16.73 2.53 Actual 17.73 3.46 –18.69 2 Left Expected –18.30 21.63 –15.43 1.71 Actual –19.77 22.18 –16.69 Right Expected 22.53 26.24 –18.79 1.82 Actual 22.58 25.65 –20.60 3 Left Expected –16.45 –1.38 –17.84 1.11 Actual –16.08 –0.43 –18.00 Right Expected 17.08 1.84 –13.24 3.27 Actual 17.69 –1.38 –15.84 View Large DISCUSSION This study described the first use of robotic assistance to implant responsive neurostimulator devices in epilepsy patients with medically refractory partial focal seizures. The main advantage of using a robot was that it allowed for high accuracy and precision when placing electrodes, and removed any chance of human error, particularly when calculating the trajectory. Further, use of the robot gives the surgeon more flexibility because the arc-less system allows trajectory freedom across multiple spatial planes.4 Moreover, using RNS is still relatively new, as it received US FDA approval as adjunctive therapy for treating medically refractory epilepsy patients in February 2013.8 By combining these 2 modalities of advanced technology, we were able to provide effective treatment while minimizing potential human error. Our study provided additional evidence that robotic assistance in implanting depth electrodes is accurate despite the long trajectory between the entry point and target. Further, the robot allowed us to make minor adjustments to the entry point in multiple dimensions without causing large deviations from the expected target. Our calculated values were accurate and acceptable. However, our sample size was very small and follow-up was short, which were limitations of this study. We anticipate that the accuracy for implanting RNS electrodes would be similar to that of other procedures (eg, DBS or SEEG electrode implantation), but additional research is required to make this claim. The patients in this study had bilateral mesial temporal lobe epilepsy, thus neither resection nor ablation were an option. We chose the RNS system because evidence has shown that it is safe and effective in this subset of patients.2,3 Further, a study showed that the RNS system is not associated with long-term cognitive decline and that patients may even show cognitive improvements due to lower seizure frequencies.9 There were multiple potential options available,10 such as vagus nerve stimulators (VNS)11 or long-term DBS,12 RNS is a closed-loop system (ie, stimulation that is not continuous) that may be ultimately more effective clinically than VNS or DBS (ie, open loop systems).13 The RNS system may not be completely free of complications. For example, a case series showed that implant-site infection and bone flap osteomyelitis occurred relatively frequently in the authors’ experience.14 They stated that the infection rate was higher than for other implantable devices (eg, DBS devices), and that this complication should be considered when deciding whether RNS is appropriate. Further, the study showed that the infection rate for infection and bone flap osteomyelitis was about 10%. None of our patients have experienced these adverse events, but it could be due to a low sample size and short follow-up. Reducing the likelihood of these events may rely on reducing risk factors (eg, improve battery life, thus reducing frequency of changing it).14 Limitations One limitation of this study is that the follow-up data are short. However, the purpose of this study was to show that robotic assistance is a viable and useful tool for implanting RNS depth electrodes. Several studies have shown that it may take several years to see the RNS system's full effects;15 thus, our patients may not see their full effects in seizure reduction until farther down the road. The main purpose of this study was to show that these 2 advanced technological modalities could be combined. However, whether there are long-term effects in terms of patient outcomes of using robotic assistance in implanting the RNS system is unclear and thus further research is needed to elucidate the possibilities. CONCLUSION Here we present a technical nuance of adding robotic assistance to implanting RNS devices in epilepsy patients. Robotic assistance in stereotactic procedures has been shown to be versatile, accurate, precise, and safe; this study shows that these advantages can be conferred during RNS implantation and that these 2 technological modalities are compatible. Disclosures Dr S Vadera is an advisor for MedTech. The other authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article. REFERENCES 1. Fountas KN, Smith JR, Murro AM, Politsky J, Park YD, Jenkins PD. Implantation of a closed-loop stimulation in the management of medically refractory focal epilepsy. Stereotact Funct Neurosurg . 2005; 83( 4): 153- 158. Google Scholar CrossRef Search ADS PubMed 2. Heck CN, King-Stephens D, Massey AD et al. Two-year seizure reduction in adults with medically intractable partial onset epilepsy treated with responsive neurostimulation: final results of the RNS System Pivotal trial. Epilepsia . 2014; 55( 3): 432- 441. Google Scholar CrossRef Search ADS PubMed 3. Meador KJ, Kapur R, Loring DW, Kanner AM, Morrell MJ. Quality of life and mood in patients with medically intractable epilepsy treated with targeted responsive neurostimulation. Epilepsy Behav . 2015; 45: 242- 247. Google Scholar CrossRef Search ADS PubMed 4. Vadera S, Chan A, Lo T et al. Frameless stereotactic robot-assisted subthalamic nucleus deep brain stimulation: case report. World Neurosurg . 2017; 97: 762.e11- 762.e14. Google Scholar CrossRef Search ADS 5. Gonzalez-Martinez J, Vadera S, Mullin J et al. Robot-assisted stereotactic laser ablation in medically intractable epilepsy: operative technique. Neurosurgery . 2014; 10: 167- 173. Google Scholar CrossRef Search ADS PubMed 6. Chan AY, Tran DK, Gill AS, Hsu FPK, Vadera S. Stereotactic robot-assisted MRI-guided laser thermal ablation of radiation necrosis and high grade glioma in the posterior cranial fossa. Neurosurg Focus . 2016; 41: E5. Google Scholar CrossRef Search ADS PubMed 7. González-Martínez J, Bulacio J, Thompson S et al. Technique, results, and complications related to robot-assisted stereoelectroencephalography. Neurosurgery . 2016; 78( 2): 169- 180. Google Scholar CrossRef Search ADS PubMed 8. FDA. Device approvals and clearances. http://www.epilepsy.com/release/2014/3/fda-approves-responsive-neurostimulation-therapy-neuropace. 2013. 9. Loring DW, Kapur R, Meador KJ, Morrell MJ. Differential neuropsychological outcomes following targeted responsive neurostimulation for partial-onset epilepsy. Epilepsia . 2015; 56( 11): 1836- 1844. Google Scholar CrossRef Search ADS PubMed 10. Chang EF, Englot DJ, Vadera S. Minimally invasive surgical approaches for temporal lobe epilepsy. Epilepsy Behav . 2015; 47: 24- 33. Google Scholar CrossRef Search ADS PubMed 11. Alsaadi TM, Laxer KD, Barbaro NM, Marks WJ Jr, Garcia PA. Vagus nerve stimulation for the treatment of bilateral independent temporal lobe epilepsy. Epilepsia . 2001; 42( 7): 954- 956. Google Scholar CrossRef Search ADS PubMed 12. Boon P, Vonck K, Herdt VD et al. Deep brain stimulation in patients with refractory temporal lobe epilepsy. Epilepsia . 2007; 48( 8): 1551- 1560. Google Scholar CrossRef Search ADS PubMed 13. Sun FT, Morrell MJ. Closed-loop neurostimulation: the clinical experience. Neurotherapeutics . 2014; 11( 3): 553- 563. Google Scholar CrossRef Search ADS PubMed 14. Wei Z, Gordon CR, Bergey GK, Sacks JM, Anderson WS. Implant site infection and bone flap osteomyelitis associated with the NeuroPace Responsive Neurostimulation System. World Neurosurg . 2016; 88: 687e1- 687e6. Google Scholar CrossRef Search ADS 15. Bergey GK, Morrell MJ, Mizrahi EM et al. Long-term treatment with responsive brain stimulation in adults with refractory partial seizures. Neurology . 2015; 84: 810- 817. Google Scholar CrossRef Search ADS PubMed Copyright © 2017 by the Congress of Neurological Surgeons
Operative Neurosurgery – Oxford University Press
Published: Mar 1, 2018
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