Responsive Neurostimulation System Research Articles

Simulated resections and responsive neurostimulator placement can optimize postoperative seizure outcomes when guided by fast ripple networks.

In medication-resistant epilepsy, the goal of epilepsy surgery is to make a patient seizure free with a resection/ablation that is as small as possible to minimize morbidity. The standard of care in planning the margins of epilepsy surgery involves electroclinical delineation of the seizure-onset zone and incorporation of neuroimaging findings from MRI, PET, single-photon emission CT and magnetoencephalography modalities. Resecting cortical tissue generating high-frequency oscillations has been investigated as a more efficacious alternative to targeting the seizure-onset zone. In this study, we used a support vector machine (SVM), with four distinct fast ripple (FR: 350-600 Hz on oscillations, 200-600 Hz on spikes) metrics as factors. These metrics included the FR resection ratio, a spatial FR network measure and two temporal FR network measures. The SVM was trained by the value of these four factors with respect to the actual resection boundaries and actual seizure-free labels of 18 patients with medically refractory focal epilepsy. Leave-one-out cross-validation of the trained SVM in this training set had an accuracy of 0.78. We next used a simulated iterative virtual resection targeting the FR sites that were of highest rate and showed most temporal autonomy. The trained SVM utilized the four virtual FR metrics to predict virtual seizure freedom. In all but one of the nine patients who were seizure free after surgery, we found that the virtual resections sufficient for virtual seizure freedom were larger in volume (P < 0.05). In nine patients who were not seizure free, a larger virtual resection made five virtually seizure free. We also examined 10 medically refractory focal epilepsy patients implanted with the responsive neurostimulator system and virtually targeted the responsive neurostimulator system stimulation contacts proximal to sites generating FR at highest rates to determine if the simulated value of the stimulated seizure-onset zone and stimulated FR metrics would trend towards those patients with a better seizure outcome. Our results suggest the following: (i) FR measures can accurately predict whether a resection, defined by the standard of care, will result in seizure freedom; (ii) utilizing FR alone for planning an efficacious surgery can be associated with larger resections; (iii) when FR metrics predict the standard-of-care resection will fail, amending the boundaries of the planned resection with certain FR-generating sites may improve outcome and (iv) more work is required to determine whether targeting responsive neurostimulator system stimulation contact proximal to FR generating sites will improve seizure outcome.

Centromedian region thalamic responsive neurostimulation mitigatesidiopathic generalized and multifocal epilepsy with focal to bilateral tonic-clonic seizures.

Although >30% of epilepsy patients have drug-resistant epilepsy (DRE), typically those with generalized or multifocal disease have not traditionally been considered surgical candidates. Responsive neurostimulation (RNS) of the centromedian (CM) region of the thalamus now appears to be a promising therapeutic option for this patient population. We present outcomes following CM RNS for 13 patients with idiopathic generalized epilepsy (IGE) and eight with multifocal onsets that rapidly generalize to bilateral tonic-clonic (focal to bilateral tonic-clonic [FBTC]) seizures. A retrospective review of all patients undergoing bilateral CM RNS by the senior author through July 2022 were reviewed. Electrodes were localized and volumes of tissue activation were modeled in Lead-DBS. Changes in patient seizure frequency were extracted from electronic medical records. Twenty-one patients with DRE underwent bilateral CM RNS implantation. For 17 patients with at least 1 year of postimplantation follow-up, average seizure reduction from preoperative baseline was 82.6% (SD = 19.0%, median = 91.7%), with 18% of patients Engel class 1, 29% Engel class 2, 53% Engel class 3, and 0% Engel class 4. There was a trend for average seizure reduction to be greater for patients with nonlesional FBTC seizures than for other patients. For patients achieving at least Engel class 3 outcome, median time to worthwhile seizure reduction was 203.5 days (interquartile range = 110.5-343.75 days). Patients with IGE with myoclonic seizures had a significantly shorter time to worthwhile seizure reduction than other patients. The surgical targeting strategy evolved after the first four subjects to achieve greater anatomic accuracy. Patients with both primary and rapidly generalized epilepsy who underwent CM RNS experienced substantial seizure relief. Subsets of these patient populations may particularly benefit from CM RNS. The refinement of lead targeting, tuning of RNS system parameters, and patient selection are ongoing areas of investigation.

Robot-assisted, CT-guided placement of responsive neurostimulator system with bilateral centromedian thalamus depth electrodes for multifocal intractable epilepsy.

The responsive neurostimulator system has become increasingly popular in the surgical management of refractory epilepsy, with targeting of various thalamic nuclei showing promising results in select patients. A 42-year-old female presented for evaluation of refractory epilepsy consisting of generalized tonic-clonic and focal seizures with preserved awareness. Phase I and II monitoring suggested multifocal bilateral epilepsy with bilateral frontal onset, and the patient underwent robot-guided bilateral centromedian thalamic placement of the RNS System. In this operative video, the authors share their institutional experience and protocol utilizing the ExcelsiusGPS robot in the placement of the RNS System in the thalamus. The video can be found here: https://stream.cadmore.media/r10.3171/2024.4.FOCVID243.

Stereotactic depth electrode placement for chronic subthreshold cortical stimulation: surgical technique video.

Neurostimulation is an increasingly common treatment option for medically intractable epilepsy. SANTE (Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy) and Responsive Neurostimulation (RNS) System are landmark neurostimulation trials that utilized either duty cycle or a responsive stimulation paradigm. A seizure-free outcome is rarely observed with responsive and duty cycle neurostimulation devices. Chronic subthreshold cortical stimulation (CSCS) is a promising treatment for adult drug-resistant epilepsy involving eloquent cortex and has demonstrated safety and efficacy. Herein, the authors describe the surgical technique as well as details of stimulation programming involved in CSCS placement to facilitate the adoption of this promising treatment. The video can be found here: https://stream.cadmore.media/r10.3171/2024.4.FOCVID2422.

Simulated resections and RNS placement can optimize post-operative seizure outcomes when guided by fast ripple networks.

In medication-resistant epilepsy, the goal of epilepsy surgery is to make a patient seizure free with a resection/ablation that is as small as possible to minimize morbidity. The standard of care in planning the margins of epilepsy surgery involves electroclinical delineation of the seizure onset zone (SOZ) and incorporation of neuroimaging findings from MRI, PET, SPECT, and MEG modalities. Resecting cortical tissue generating high-frequency oscillations (HFOs) has been investigated as a more efficacious alternative to targeting the SOZ. In this study, we used a support vector machine (SVM), with four distinct fast ripple (FR: 350-600 Hz on oscillations, 200-600 Hz on spikes) metrics as factors. These metrics included the FR resection ratio (RR), a spatial FR network measure, and two temporal FR network measures. The SVM was trained by the value of these four factors with respect to the actual resection boundaries and actual seizure free labels of 18 patients with medically refractory focal epilepsy. Leave one out cross-validation of the trained SVM in this training set had an accuracy of 0.78. We next used a simulated iterative virtual resection targeting the FR sites that were highest rate and showed most temporal autonomy. The trained SVM utilized the four virtual FR metrics to predict virtual seizure freedom. In all but one of the nine patients seizure free after surgery, we found that the virtual resections sufficient for virtual seizure freedom were larger in volume (p<0.05). In nine patients who were not seizure free, a larger virtual resection made five virtually seizure free. We also examined 10 medically refractory focal epilepsy patients implanted with the responsive neurostimulator system (RNS) and virtually targeted the RNS stimulation contacts proximal to sites generating FR at highest rates to determine if the simulated value of the stimulated SOZ and stimulated FR metrics would trend toward those patients with a better seizure outcome. Our results suggest: 1) FR measures can accurately predict whether a resection, defined by the standard of care, will result in seizure freedom; 2) utilizing FR alone for planning an efficacious surgery can be associated with larger resections; 3) when FR metrics predict the standard of care resection will fail, amending the boundaries of the planned resection with certain FR generating sites may improve outcome; and 4) more work is required to determine if targeting RNS stimulation contact proximal to FR generating sites will improve seizure outcome.

Characterizing Seizure-Onset Patterns With the Responsive Neurostimulation System.

The responsive neurostimulation system (RNS) aims to improve seizures by delivering electrical stimulation in response to epileptiform patterns detected by electrocorticograms. Seizure-onset patterns (SOPs) correspond to outcomes in intracranial EEG (IC-EEG), although whether this is true for RNS is unknown. This study characterizes common RNS SOPs and correlates them with seizure outcomes. Among 40 patients with RNS implants, long-episode electrocorticogram characteristics of each patient's seizures were classified by visual analysis as one of the eight patterns previously described in IC-EEG. Correlation between each type of SOP and eventual seizure outcome was analyzed, with ≥50% improvement in a number of patient-reported seizure counts defined as a favorable outcome. Across 263 LEs analyzed, the most common SOP observed was low-voltage fast activity. There was no difference between the distribution of RNS SOPs and that of IC-EEG SOPs described in the literature (Kolmogorov-Smirnov test, P = 0.98). Additionally, there was no correlation between any particular SOP and favorable outcomes (Fisher's omnibus test, P = 0.997). This initial description of RNS SOPs finds them to be similar to previously described IC-EEG SOPs, which suggests similar prognostic/therapeutic potential. However, we found that RNS efficacy is independent of patient SOP, suggesting that RNS is likely an equally effective treatment for all SOPs. Future research on stimulation parameters for particular RNS SOPs and correlation with IC-EEG SOPs in the same patients would be instrumental in guiding personalized neurostimulation.

271 A Retrospective, Chart Review Study of the Efficacy and Safety of the RNS System in Pediatric Populations for Medically Refractory Focal Epilepsy

INTRODUCTION: The Responsive Neurostimulation System (RNS) (NeuroPace, Mountain View) is a direct intracranial neurostimulator that is FDA-approved for adults with medically refractory focal epilepsy. There currently exists limited data regarding its efficacy and safety in pediatric populations. METHODS: A retrospective chart review was conducted of pediatric patients treated with the RNS System between January 1, 2019 and December 31, 2021 at Rady Children’s Hospital for at least one year. Data collected included percent change in median disabling seizure frequency from baseline at years 1, 2, and 3, as well as device-related serious adverse events. RESULTS: Twenty patients with medically refractory focal epilepsy were identified who had been treated with the RNS System for at least one year. Median duration of follow-up was 24 months (interquartile range [IQR]: 15-35 months) The median percent reduction in disabling seizures was 29% (N = 20, IQR = 0-84%) at 1 year, 53% (N = 12, IQR = -5-81%) at 2 years, and 67% (N = 4, IQR = 25-100%) at 3 years. 40% of patients reported a &gt;90% reduction in median disabling seizure frequency, and 25% were seizure-free at last follow-up. Reductions in median seizure frequency were comparable based on patient age, age at seizure onset, neuroimaging findings, and prior intracranial monitoring. Zero patients experienced implant site infections. One patient (5%) required lead revision, and another patient (5%) had a spontaneous intraparenchymal hemorrhage at the generator site 2 years after implantation that resolved with expectant management. Neither of these events were associated with long-lasting neurological complications. CONCLUSIONS: The RNS System is a safe and efficacious treatment for pediatric patients with medically refractory focal epilepsy.

194 Responsive Neurostimulation Targeting the Centromedian Nucleus of the Thalamus Improves Seizure Control in Idiopathic Generalized Epilepsy and Select Multifocal Disease

INTRODUCTION: Although more than 30% of epilepsy patients are drug resistant, many have not traditionally been considered surgical candidates due to generalized or multifocal disease. However, responsive neurostimulation (RNS) of the centromedian nucleus (CM) of the thalamus appears promising for this patient population. We present outcomes following CM RNS for patients with idiopathic generalized epilepsy (IGE) or multifocal disease, with subgroup analyses of patients’ seizure types and targeting methodology. METHODS: 21 patients with drug resistant epilepsy underwent bilateral CM RNS implantation. Electrodes were localized and volumes of tissue activation (VTAs) were modeled in Lead-DBS. Outcome measures were extracted from electronic medical records. Clinical outcomes over time were compared between patients’ seizure types and RNS recorded long-episodes, and VTA overlap with thalamic nuclei was compared between patients with direct and indirect targeting methodologies. RESULTS: For patients with at least 1-year of follow up, average seizure reduction from pre-operative baseline was 81.3%, with 3 Engel class 1 patients, 5 Engel class 2, 8 Engel class 3, and 0 Engel class 4. Average seizure reduction was greatest for non-lesional multifocal patients. Average time to worthwhile seizure reduction was 217 days, and was shortest for myoclonic IGE patients. Long-episodes were associated with seizure reduction in IGE patients only. Direct targeting led to more anterior and medial electrodes with greater VTA overlap with CM. CONCLUSIONS: CM RNS may provide significant relief for IGE and multifocal epilepsy patients. Subsets of these patient populations may particularly benefit from CM RNS. Direct targeting may facilitate more selective stimulation of the CM. The refinement of stimulation targeting, tuning of RNS system parameters, and deliberate patient selection are ongoing areas of investigation.

Circadian changes in aperiodic activity are correlated with seizure reduction in patients with mesial temporal lobe epilepsy treated with responsive neurostimulation.

Responsive neurostimulation (RNS) is an established therapy for drug-resistant epilepsy that delivers direct electrical brain stimulation in response to detected epileptiform activity. However, despite an overall reduction in seizure frequency, clinical outcomes are variable, and few patients become seizure-free. The aim of this retrospective study was to evaluate aperiodic electrophysiological activity, associated with excitation/inhibition balance, as a novel electrographic biomarker of seizure reduction to aid early prognostication of the clinical response to RNS. We identified patients with intractable mesial temporal lobe epilepsy who were implanted with the RNS System between 2015 and 2021 at the University of Utah. We parameterized the neural power spectra from intracranial RNS System recordings during the first 3 months following implantation into aperiodic and periodic components. We then correlated circadian changes in aperiodic and periodic parameters of baseline neural recordings with seizure reduction at the most recent follow-up. Seizure reduction was correlated significantly with a patient's average change in the day/night aperiodic exponent (r = .50, p = .016, n = 23 patients) and oscillatory alpha power (r = .45, p = .042, n = 23 patients) across patients for baseline neural recordings. The aperiodic exponent reached its maximum during nighttime hours (12 a.m. to 6 a.m.) for most responders (i.e., patients with at least a 50% reduction in seizures). These findings suggest that circadian modulation of baseline broadband activity is a biomarker of response to RNS early during therapy. This marker has the potential to identify patients who are likely to respond to mesial temporal RNS. Furthermore, we propose that less day/night modulation of the aperiodic exponent may be related to dysfunction in excitation/inhibition balance and its interconnected role in epilepsy, sleep, and memory.

A Comparison of Neuropsychological Outcomes following Responsive Neurostimulation and Anterior Temporal Lobectomy in Drug-Resistant Epilepsy.

Neuropsychological outcomes following temporal lobe resection for drug-resistant epilepsy (DRE) are well established. For instance, left anterior temporal lobectomy (LATL) is associated with a greater risk for cognitive morbidity compared to right (RATL). However, the impact of neuromodulatory devices, specifically responsive neurostimulation (RNS), remains an area of active interest. There are currently no head-to-head comparisons of neuropsychological outcomes after surgical resection and neuromodulation. This study reports on a cohort of 21 DRE patients with the RNS System who received comprehensive pre- and post-implantation neuropsychological testing. We compared both cognitive and seizure outcomes in the RNS group to those of 307 DRE patients who underwent LATL (n = 138) or RATL (n = 169). RNS patients had higher seizure rates pre-intervention. While fewer in the RNS group achieved Class I Engel outcomes compared to the ATL cohorts, RNS patients also showed seizure frequency declines from pre- to post-intervention that were similar to those who underwent resective surgery. Moreover, the RNS and RATL groups were similar in their neuropsychological outcomes, showing no significant cognitive decline post-intervention. In contrast, the LATL group notably declined in object naming and verbal list learning. Direct comparisons like this study may be used to guide clinicians in shared decision making to tailor management plans for patients' overall treatment goals.

Long-term outcomes after responsive neurostimulation for treatment of refractory epilepsy: a single-center experience of 100 cases.

Despite antiepileptic drugs, more than 30% of people with epilepsy continue to have seizures. Patients with such drug-resistant epilepsy (DRE) may undergo invasive treatment such as resection, laser ablation of the epileptogenic focus, or vagus nerve stimulation, but many are not candidates for epilepsy surgery or fail to respond to such interventions. Responsive neurostimulation (RNS) provides a neuromodulatory option. In this study, the authors present a single-center experience with the use of RNS over the last 5 years to provide long-term control of seizures in patients with DRE with at least 1 year of follow-up. The authors performed a retrospective analysis of a prospectively collected single-center database of consecutive DRE patients who underwent RNS system implantation from September 2015 to December 2020. Patients were followed-up postoperatively to evaluate seizure freedom and complications. One hundred patients underwent RNS placement. Seven patients developed infections: 2 responded to intravenous antibiotic therapy, 3 required partial removal and salvaging of the system, and 2 required complete removal of the RNS device. No postoperative tract hemorrhages, strokes, device migrations, or malfunctions were documented in this cohort. The average follow-up period was 26.3 months (range 1-5.2 years). In terms of seizure reduction, 8 patients had 0%-24% improvement, 14 had 25%-49% improvement, 29 experienced 50%-74% improvement, 30 had 75%-99% improvement, and 19 achieved seizure freedom. RNS showed significantly better outcomes over time: patients with more than 3 years of RNS therapy had 1.8 higher odds of achieving 75% or more seizure reduction (95% CI 1.07-3.09, p = 0.02). Also, patients who had undergone resective or ablative surgery prior to RNS implantation had 8.25 higher odds of experiencing 50% or more seizure reduction (95% CI 1.05-65.1, p = 0.04). Responsive neurostimulator implantation achieved 50% or more seizure reduction in approximately 80% of patients. Even in patients who did not achieve seizure freedom, significant improvement in seizure duration, severity, or postictal state was reported in more than 68% of cases. Infection (7%) was the most common complication. Patients with prior resective or ablative procedures and those who had been treated with RNS for more than 3 years achieved better outcomes.

Long-Term Intracranial EEG Lateralization of Epileptogenicity in Patients With Confirmed or Suspected Bilateral Mesial Temporal Lobe Onsets During Epilepsy Surgical Evaluation.

The data resulting from epilepsy surgical evaluation are occasionally unclear in cases of mesial temporal lobe (MTL) epilepsy. Long-term intracranial EEG (iEEG) collected by the Responsive Neurostimulation (RNS) System may be an approach for capturing additional seizure data while treating patients with neurostimulation. We reviewed iEEG seizure lateralization and clinical outcomes in bilateral MTL patients at University of Utah. Long-term RNS System iEEG seizure lateralization was compared with pre-RNS System lateralization obtained during surgical evaluation. Safety and clinical outcomes were extracted retrospectively from patient records. Twenty-six patients received an RNS System with bilateral MTL leads. Fifteen of the patients had adequate follow-up to report clinical outcomes ( > 1 year), and 25 patients had enough recorded data ( > 6 months) to perform iEEG analysis. Median percent reduction in clinical seizures at last follow-up was 58%, and 40% reported being seizure-free at last follow-up, for variable durations. The electrographic seizure lateralization (unilateral vs. bilateral) differed between surgical evaluation and long-term iEEG in 44% of our patients. In the subset of eight patients (32%) who had only unilateral seizures recorded during surgical evaluation, but were implanted with bilateral MTL leads based on bilateral interictal epileptiform discharges, 62% (5/8) had bilateral seizures recorded on long-term iEEG. Interestingly, in the 18 patients who had bilateral seizures recorded during surgical evaluation, 28% (5/18) were found to be unilateral on long-term iEEG. Our data suggest that RNS System implantation in suspected bilateral MTL cases may be an option to assess a patient's true seizure lateralization on long-term iEEG. Responsive neuromodulation should be considered before resection or ablation in cases that have evaluation data suggesting bilaterality.

Clinical outcomes following responsive neurostimulation implantation: a single center experience.

Responsive neurostimulation (RNS) is an implantable device for persons with medically refractory focal-onset epilepsy. We report a single-center experience for RNS outcomes with special focus on stereoelectroencephalography (sEEG) for seizure onset localization. We performed retrospective review of patients with drug resistant focal epilepsy implanted with the RNS System for a minimum of six months between July 2014 and July 2019. Records were reviewed for demographic data, epilepsy duration, seizure frequency, number of prior antiepileptic drugs (AEDs), number of AEDs at RNS System implantation, prior epilepsy surgery or device use, previous seizure localization with sEEG, and RNS system information. Clinical response was defined as a 50% reduction in seizures. Differing response rates were calculated using Fisher Exact test. 30 patients met inclusion criteria. Seventeen (57%) underwent previous sEEG. Average clinical follow up was 3.0 years. Overall response rate was 70%. Median seizure reduction was 74.5%. Response rate was 82.3% for patients with sEEG compared to 53.8% without (p = 0.08); 37.5% for prior epilepsy surgery compared to 81.8% without (p = 0.02); 70% for mesial temporal onset; 50% for previous vagal nerve stimulator compared to 77.3% without (p = 0.13). Our response rates match or surpass outcome metrics of previous studies. Although limited by small study size, subpopulation analyses show positive response rates in patients with previous sEEG versus no sEEG and in temporal versus extratemporal pathology. Additional research is needed to evaluate efficacy of RNS in patients with previous epilepsy surgery, and utility of sEEG in this population.

Safety and efficacy of a novel responsive neurostimulation system in China for drug-refractory focal epilepsy: The first-in-man study.

Safety and efficacy of a novel responsive neurostimulation system in China for drug-refractory focal epilepsy: The first-in-man study.

Responsive Neurostimulation for Management of Refractory Precuneus Onset Epilepsy: A Case Report

Posterior quadrant epilepsy is relatively uncommon and refractory seizures from these regions are difficult to diagnose and manage. A 28-year-old woman presented for evaluation of her seizures. Scalp Electroencephalogram (EEG) showed seizures with independent onset over the right posterior and left anterior regions. Positron emission tomography (PET) scans revealed multiple regions of hypometabolism in the brain with maximum decrease in metabolism seen over the left and right precuneus and both occipital lobes. Magnetoencephalography (MEG) revealed epileptogenic dipoles over bilateral precuneus regions. Intracranial EEG revealed seizure onset from the left precuneus and left frontal regions with rapid generalization. She underwent Responsive Neurostimulation System (RNS) implantation targeting the left precuneus and left frontal regions for network modulation. She has had a 90 percent seizure reduction and remains on 2 medications as she continues to follow up in clinic. Posterior quadrant epilepsy remains a challenging condition to manage, and the use of neuromodulation may improve response rates and improve our understanding of these networks. Definite guidelines on location of electrode placement of RNS in such cases remain absent and improved understanding of such seizure networks is expected to improve our ability to target therapeutic nodes accurately to achieve greater seizure control.

Infraclavicular de novo placement of a responsive neurostimulator for a patient with eloquent glioma-associated epilepsy: illustrative case.

The authors present a 50-year-old female with high-grade glioma involving the motor cortex as the cause of her drug-resistant epilepsy (DRE). Responsive neurostimulation (RNS) was chosen for epilepsy treatment. Due to concerns regarding the generator impeding the regular imaging surveillance required for treatment and monitoring of her glioma, surgeons placed the internal pulse generator (IPG) within an infraclavicular chest pocket. Implantation of the RNS device and IPG within the infraclavicular pocket was uneventful. However, both subdural and depth electrodes were used and connected to the IPG, and subdural electrodes are considerably shorter than depth electrodes (37 vs 44 cm). The shorter strip leads presumably generated significant tension, leading to fracture of the leads. Therefore, surgery was repeated using only depth electrodes for more length and less tension. The device has good-quality electrocorticography signals that continue to be used for device programming. The seizure burden was reduced, and quality of life improved for the patient. The RNS system with infraclavicular IPG placement reduced the seizure burden and improved the quality of life of a patient with glioma-associated epilepsy. Surgeons may consider the infraclavicular location as an alternative site for implantation for RNS candidates who require recurrent intracranial magnetic resonance imaging.

Deep net detection and onset prediction of electrographic seizure patterns in responsive neurostimulation.

Managing the progress of drug-resistant epilepsy patients implanted with the Responsive Neurostimulation (RNS) System requires the manual evaluation of hundreds of hours of intracranial recordings. The generation of these large amounts of data and the scarcity of experts' time for evaluation necessitate the development of automatic tools to detect intracranial electroencephalographic (iEEG) seizure patterns (iESPs) with expert-level accuracy. We developed an intelligent system for identifying the presence and onset time of iESPs in iEEG recordings from the RNS device. An iEEG dataset from 24 patients (36 293 recordings) recorded by the RNS System was used for training and evaluating a neural network model (iESPnet). The model was trained to identify the probability of seizure onset at each sample point of the iEEG. The reliability of the net was assessed and compared to baseline methods, including detections made by the device. iESPnet performance was measured using balanced accuracy and the F1 score for iESP detection. The prediction time was assessed via both the error and the mean absolute error. The model was evaluated following a hold-one-out strategy, and then validated in a separate cohort of 26 patients from a different medical center. iESPnet detected the presence of an iESP with a mean accuracy value of 90% and an onset time prediction error of approximately 3.4 s. There was no relationship between electrode location and prediction outcome. Model outputs were well calibrated and unbiased by the RNS detections. Validation on a separate cohort further supported iESPnet applicability in real clinical scenarios. Importantly, RNS device detections were found to be less accurate and delayed in nonresponders; therefore, tools to improve the accuracy of seizure detection are critical for increasing therapeutic efficacy. iESPnet is a reliable and accurate tool with the potential to alleviate the time-consuming manual inspection of iESPs and facilitate the evaluation of therapeutic response in RNS-implanted patients.

ID: 222352 Vasospasm Secondary to Responsive Neurostimulator Placement: A Previously Unreported Complication

The Responsive Neurostimulation (RNS) system is a therapy for patients with drug-resistant epilepsy who are not candidates for surgical resection of a seizure focus. The system involves long-term implantation of subdural or depth lead connected to a neurostimulator that detects incipient epileptic activity and delivers stimulation to control seizure spread. The intra-cranial leads are implanted as close as possible to the epileptic focus or foci to optimize detection and therapeutic stimulation ability. As with other brain-machine interface systems, RNS systems are subject to hardware-related complications. As a relatively new therapy option, the adverse effects of long-term implantation are still being clarified. We present a case report of a patient that developed severe vasospasm after RNS implantation.

ID: 218310 Responsive Neurostimulation (RNS) of Thalamic Nuclei in Pediatric Drug-Resistant Epilepsy (DRE)

Reactive neurostimulation (RNS) is an FDA-approved form of neuromodulation to treat patients with drug-resistant epilepsy (DRE) who are ineligible or refractory to surgical treatment1,2. However, the FDA approval only extends to use in patients with one or two epileptogenic foci3, which would be used as the target locations for neurostimulation. The population of patients with multifocal or non-localizable DRE may also benefit from applying the RNS system. Recent literature has shown possible efficacy (in terms of seizure reduction) of thalamic RNS stimulation in two patients with Lennox-Gastaut syndrome (LGS) and multifocal epilepsy4, particularly targeting the centromedian nucleus. We hypothesized that reactive neurostimulation of thalamic nuclei might be effective in seizure reduction for patients with multifocal or non-localizable DRE, with or without LGS. The purpose of this study is to provide the outcomes for pediatric patients at Texas Children’s Hospital after thalamic RNS implantation.

Vasospasm secondary to responsive neurostimulator placement: a previously unreported complication. Illustrative case.

The Responsive Neurostimulation (RNS) system is an implantable device for patients with drug-resistant epilepsy who are not candidates for resection of a seizure focus. As a relatively new therapeutic, the full spectrum of adverse effects has yet to be determined. A literature review revealed no previous reports of cerebral vasospasm following RNS implantation. A 35-year-old man developed severe angiographic and clinical vasospasm following bilateral mesial temporal lobe RNS implantation. He initially presented with concerns for status epilepticus 8 days after implantation. On hospital day 3, a decline in his clinical examination prompted imaging studies that revealed a left middle cerebral artery (MCA) stroke with angiographic evidence of severe vasospasm of the left internal carotid artery (ICA), MCA, anterior cerebral artery (ACA), and right ICA and ACA. Despite improvements in angiographic vasospasm after appropriate treatment, a thrombus developed in the posterior M2 branch, requiring mechanical thrombectomy. Ultimately, the patient was stabilized and discharged to a rehabilitation facility with residual cognitive and motor deficits. Cerebral vasospasm as a cause of ischemic stroke after uneventful RNS implantation is exceedingly rare, yet demands particular attention given the potential for severe consequences and the growing number of patients receiving RNS devices.