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.

Design of a Multicenter, Randomized Controlled Trial for the Treatment of Peripheral Neuropathic Pain (COMFORT Study) with a Micro-Implantable Pulse Generator.

Peripheral Nerve Stimulation (PNS) is an established therapy for chronic neuropathic pain of peripheral origin, typically following nerve injury. However, there is a paucity of Randomized Controlled Trials (RCTs) demonstrating the therapeutic benefits of PNS. The goals of the current study (COMFORT Study) are to document the safety and efficacy of the Nalu Neurostimulation in a PNS RCT, compared to conventional medical management (CMM). This is a prospective, multicenter, RCT evaluating the treatment of neuropathic pain with PNS therapy. One of the following four regions will be targeted for treatment: low back, shoulder, knee or foot/ankle. Consented subjects will undergo a baseline evaluation, after which they are randomized 2:1 (PNS+CMM arm to CMM arm). Subjects randomized to PNS+CMM arm will undergo a trial implant period using best clinical practices. Subjects who pass the trial phase, by showing a ≥ 50% reduction in pain relative to baseline, will receive the permanent implant. All subjects receiving a permanent implant will be followed for a total of 36 months. At the 3-month primary end point, subjects in CMM arm will be given the option to crossover into PNS+CMM arm, beginning with a trial implant. The study duration is expected to be 5.5 years from first enrollment to last follow-up of last subject and subsequent study closure. Adverse events will be captured throughout the study. The COMFORT study, described here, has the potential to demonstrate the efficacy and safety of the Nalu Neurostimulation System in the treatment of peripheral neuropathy. Results of this study will be the first Level-I evidence, out to 36 months, validating the use of this PNS system in the treatment of chronic pain. This study is designed to enroll the largest cohort, to date, of subjects comparing PNS+CMM vs CMM alone.

A 9-V Wireless Power Receiver IC With 74.2% Power Conversion Efficiency and Integrated Bidirectional Telemetries for Implantable Neurostimulation Systems in Standard CMOS

A 9-V Wireless Power Receiver IC With 74.2% Power Conversion Efficiency and Integrated Bidirectional Telemetries for Implantable Neurostimulation Systems in Standard CMOS

Adverse Events with Hypoglossal Nerve Stimulation in the Treatment of Obstructive Sleep Apnea-A Systematic Review of Clinical Trials and Real-World Data.

Background/Objectives: Hypoglossal nerve stimulation (HNS) emerged as an alternative treatment for patients with obstructive sleep apnea (OSA) a decade ago. Long-term clinical trials and real-world data show that HNS treatment provides significant and sustained improvements in both OSA disease control and quality-of-life measures over time. Given the nature of HNS treatment, with the requirement of using an implantable neurostimulation system, patient safety is a critical domain in the assessment of this technology. The objective of this review was to evaluate adverse events (AEs) and complications with HNS therapy in a systematic review of published evidence. Methods: Medline, Cochrane, and Web of Science were systematically searched to identify randomized controlled and real-world observational studies reporting relevant outcomes with HNS therapy for treatment of OSA that included procedure-, device-, and treatment-related AEs. Results: Out of 418 articles screened, 27 were reviewed for eligibility, and 17 studies, the majority found to have low-to-moderate risk of bias, with data on 1962 patients were included for further analysis. Across included studies, reporting of AEs was heterogeneous with regard to the classifications used and the extent of reporting. Over an average follow-up duration of 17.5 ± 16.9 months, the pooled mortality rate was 0.01% (95% CI = 0.0 to 0.2%), with all reported deaths being unrelated to HNS treatment. The HNS system survival probability over the follow-up time of 60 months was 0.9834 (95% CI = 0.9768 to 0.9882), with infections and request for removal by patients being the most common indications. The pooled surgical revision rate was 0.08% (95% CI 0.0 to 0.2%). Most reported treatment-related side effects were transient stimulation-related discomfort (0.08%, 95% CI = 0.0 to 0.2%) and tongue abrasions (0.07%, 95% CI = 0.0 to 0.2%). Based on the systematic review, a standardized set of endpoints was defined, aiming to harmonize safety data relevant to HNS therapy. Conclusions: In this systematic review, HNS therapy for treatment of OSA is associated with a positive patient safety profile. AEs occur mainly at device implantation and during the treatment acclimatization period. Due to a lack of available evidence, partially implantable HNS systems are underrepresented in this review, which limits the generalizability of the results. Significant heterogeneity was found for adverse event reporting. A framework for reporting HNS outcomes that includes AEs and side effects is proposed to facilitate comparability of the reported data.

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.

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.

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.

50‐3: Invited Paper: An Active‐Matrix High‐Channel‐Count Neurostimulation System Enabled by Flexible Thin‐Film Transistors

Advanced neurostimulation systems require intimate interface with brain or peripheral nervous system to provide a therapeutic modulation for patients experiencing neural function loss. To achieve these, it requires stimulators with high‐channel counts and mechanical flexibility. In this invited paper, we showed a 4T1C neurostimulation pixel circuit with an active‐matrix architecture, offering the opportunity for high‐channel counts. In addition, a 4‐mask photolithographic process for highly uniform organic thin‐film transistor (OTFT) integrated system was demonstrated for mechanical flexibility, which shows a high device yield of 100% (50/50) and small device variation in threshold voltage of 0.64 V and in mobility of 4.9%. By implementing OTFTs to this novel neurostimulation architecture, we fabricated an OTFT‐based high‐channel‐count neurostimulation system, showing a high stimulator yield of 71.0% and small variation of 15.6% for the output stimulation currents among pixels.

Motor Behavior Regulation of Rat Robots Using Integrated Electrodes Stimulated by Micro-Nervous System.

As a cutting-edge technology, animal robots based on living organisms are being extensively studied, with potential for diverse applications in the fields of neuroscience, national security, and civil rescue. However, it remains a significant challenge to reliably control the animal robots with the objective of protecting their long-term survival, and this has seriously hindered their practical implementation. To address this issue, this work explored the use of a bio-friendly neurostimulation system that includes integrated stimulation electrodes together with a remote wireless stimulation circuit to control the moving behavior of rat robots. The integrated electrodes were implanted simultaneously in four stimulation sites, including the medial forebrain bundle (MFB) and primary somatosensory cortex, barrel field (S1BF). The control system was able to provide flexibility in adjusting the following four stimulation parameters: waveform, amplitude, frequency, and duration time. The optimized parameters facilitated the successful control of the rat's locomotion, including forward movement and left and right turns. After training for a few cycles, the rat robots could be guided along a designated route to complete the given mission in a maze. Moreover, it was found that the rat robots could survive for more than 20 days with the control system implanted. These findings will ensure the sustained and reliable operation of the rat robots, laying a robust foundation for advances in animal robot regulation technology.

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.

Prosthetic Visual Acuity with the PRIMA Subretinal Microchip in Patients with Atrophic Age-Related Macular Degeneration at 4 Years Follow-up

ObjectiveTo assess the efficacy and safety of the PRIMA neurostimulation system with a subretinal microchip for improving visual acuity (VA) in patients with geographic atrophy (GA) due to age-related macular degeneration (AMD) at 48-months post-implantation. DesignFirst-in-human clinical trial of the PRIMA subretinal prosthesis in patients with atrophic AMD, measuring best-corrected ETDRS VA (Clinicaltrials.gov NCT03333954). SubjectsFive patients with GA, no foveal light perception and VA of logMAR 1.3 to 1.7 (20/400-20/1000) in their worse-seeing “study” eye. MethodsIn patients subretinally implanted with a photovoltaic neurostimulation array containing 378 pixels of 100 μm in size, the VA was measured with and without the PRIMA system using ETDRS charts at 1 meter. The system’s external components, augmented reality glasses and pocket computer, provide image processing capabilities, including zoom. Main Outcome MeasuresVA using ETDRS charts with and without the system, as well as light sensitivity in the central visual field, measured by Octopus perimetry. Anatomical outcomes demonstrated by fundus photography and optical coherence tomography up to 48-months post-implantation. ResultsAll five subjects met the primary endpoint of light perception elicited by the implant in the scotoma area. In one patient the implant was incorrectly inserted into the choroid. One subject died 18-months post-implantation due to study-unrelated reason. ETDRS VA results for the remaining three subjects are reported herein. Without zoom, VA closely matched the pixel size of the implant: 1.17 ± 0.13 pixels, corresponding to mean logMAR 1.39, or Snellen 20/500, ranging from 20/438 to 20/565. Using zoom at 48 months, subjects improved their VA by 32 ETDRS letters versus baseline (SE 5.1) 95% CI[13.4,49.9], p<0.0001. Natural peripheral visual function in the treated eye did not decline after surgery, nor during the 48 months follow-up period (p=0.08). ConclusionsSubretinal implantation of PRIMA in subjects with GA suffering from profound vision loss due to AMD is feasible and well tolerated, with no reduction of natural peripheral vision up to 48-months. Prosthetic central vision provided by photovoltaic neurostimulation enabled patients to reliably recognize letters and sequences of letters, and with zoom it improved VA of up to eight ETDRS lines.

Abstract 30: Pharyngeal Electric Stimulation: The Initial U.S. Experience With a Novel Device for Treatment of Severe Dysphagia After Stroke

Background: Based on over 20 years of international research, FDA recently granted De Novo classification to the Phagenyx® Neurostimulation System for pharyngeal electrical stimulation (PES) for patients with severe dysphagia post stroke. Subjects &amp; Methods: We report on the design and outcomes of the first U.S. post market multi-center experience with the Phagenyx® Neurostimulation System (Phagenesis Limited, Manchester, UK). Eligible patients were determined to have severe dysphagia post-stroke (ischemic or hemorrhagic) by the treating stroke neurologists (MD) and standard assessments by Speech-Language Pathologists (SLPs). Treatment was implemented in addition to standard of care during hospitalization with institutional informed consents obtained prior to treatment. PES stimulation levels were optimized for each patient and each treatment through sensory threshold and tolerance testing by the SLPs. This was followed by a fixed 10 minute treatment session. The treatment regimen was: 1 treatment per day, 10 min/day x 3 days with interim speech therapy reassessment. Treatment could be extended up to 3 additional treatments for a total of 6 treatments if deemed necessary by medical team. SLPs monitored for adverse events during the optimization and treatment. Results: PES was administered to a minimum of 5 patients at each participating institution during the initial implementation. An instrumental assessment was completed at the conclusion of the treatment period as indicated, showing outcomes that ranged from improved secretion management and diet advancement, to swallow restoration. Patient experiences and suggestions were captured and will be presented. Conclusions: A novel FDA-approved PES device for treatment of severe dysphagia shows a potential to be safely tolerated with the magnitude of swallowing improvement and restoration similar to the pivotal trials conducted overseas. Final results of the multi-center study will be presented at the meeting.

Problems in organizing neurosurgical care for patients with Parkinson's disease in the Russian Federation

Currently, there are some problems in the Russian Federation complicating development of neurosurgical care for patients with Parkinson's disease (PD). In 2022, neurologists - movement disorders specialists were surveyed to analyze situation with PD pharmacological treatment and referral of patients for surgical treatment in Russian constituent entities. Data on neurosurgical treatment of PD were obtained by collecting information on the surgical activity of medical institutions in the Russian Federation. Most hospitals involved in PD treatment took part in this study. The state of neurosurgical care for patients with PD is analyzed and possible ways to improve the quality of treatment are discussed. Over the past 20 years, a system of neurosurgical care for patients with PD has been formed in 14 centers in the Russian Federation (2022). Obstacles to its further development can be divided into 3 categories: problems of patient selection and routing, complexity of organization and financing surgeries, and imperfect postoperative patient management. Ways to overcome these obstacles imply expanding the network of centers for extrapyramidal diseases, development of domestic neurostimulation systems, improving the distribution of quotas taking into account the capabilities of hospitals, specialized training of neurologists for extrapyramidal centers and neurosurgeons for deep brain stimulation centers, adequate financing and systematization of postoperative management of patients with PD.

Adaptive fuzzy iterative learning control based neurostimulation system and in-silico evaluation.

Closed-loop neural stimulation has been an effective treatment for epilepsy patients. Currently, most closed-loop neural stimulation strategies are designed based on accurate neural models. However, the uncertainty and complexity of the neural system make it difficult to build an accurate neural model, which poses a significant challenge to the design of the controller. This paper proposes an Adaptive Fuzzy Iterative Learning Control (AFILC) framework for closed-loop neural stimulation, which can realize neuromodulation with no model or model uncertainty. Recognizing the periodic characteristics of neural stimulation and neuronal firing, Iterative Learning Control (ILC) is employed as the primary controller. Furthermore, a fuzzy optimization module is established to update the internal parameters of the ILC controller in real-time. This module enhances the anti-interference ability of the control system and reduces the influence of initial controller parameters on the control process. The efficacy of this strategy is evaluated using a neural computational model. The simulation results validate the capability of the AFILC strategy to suppress epileptic states. Compared with ILC-based closed-loop neurostimulation schemes, the AFILC-based neurostimulation strategy has faster convergence speed and stronger anti-interference ability. Moreover, the control algorithm is implemented based on a digital signal processor, and the hardware-in-the-loop experimental platform is implemented. The experimental results show that the control method has good control performance and computational efficiency, which provides the possibility for future application in clinical research.

Results From a Prospective, Clinical Study (US-nPower) Evaluating a Miniature Spinal Cord Stimulator for the Management of Chronic, Intractable Pain

BACKGROUND: Chronic, intractable, neuropathic pain is readily treatable with spinal cord stimulation (SCS). Technological advancements, including device miniaturization, are advancing the field of neuromodulation. OBJECTIVES: We report here the results of an SCS clinical trial to treat chronic, low back and leg pain, with a micro-implantable pulse generator (micro-IPG). STUDY DESIGN: This was a single-arm, prospective, multicenter, postmarket, observational study. SETTING: Patients were recruited from 15 US-based comprehensive pain centers. METHODS: This open-label clinical trial was designed to evaluate the performance of the Nalu™ Neurostimulation System (Nalu Medical, Inc., Carlsbad, CA) in the treatment of low back and leg pain. Patients, who provided informed consent and were successfully screened for study entry, were implanted with temporary trial leads. Patients went on to receive a permanent implant of the leads and micro-IPG if they demonstrated a &gt;= 50% reduction in pain during the temporary trial period. Patient-reported outcomes (PROs), such as pain scores, functional disability, mood, patient impression of change, comfort, therapy use profile, and device ease of use, were captured. RESULTS: At baseline, the average pain Visual Analog Scale (VAS) score was 72.1 ± 17.9 in the leg and 78.0 ± 15.4 in the low back. At 90 days following permanent implant (end of study), pain scores improved by 76% (VAS 18.5 ± 18.8) in the leg and 75% (VAS 19.7 ± 20.8) in the low back. Eighty-six percent of both leg pain and low back pain patients demonstrated a &gt;= 50% reduction in pain at 90 days following implant. The comfort of the external wearable (Therapy Disc and Adhesive Clip) was rated 1.16 ± 1.53, on average, at 90 days on an 11-point rating scale (0 = very comfortable, 10 = very uncomfortable). All PROs demonstrated statistically significant symptomatic improvement at 90 days following implant of the micro-IPG. LIMITATIONS: Limitations of this study include the lack of long-term results (beyond 90 days) and a relatively small sample size of 35 patients who were part of the analysis; additionally, there was no control arm or randomization as this was a single-arm study, without a comparator, designed to document the efficacy and safety of the device. Therefore, no direct comparisons to other SCS systems were possible. CONCLUSIONS: This clinical study demonstrated profound leg and low back pain relief in terms of overall pain reduction, as well as the proportion of therapy responders. The study patients reported the wearable aspects of the system to be very comfortable. KEY WORDS: Spinal cord stimulation, chronic pain, radiculopathy, micro-IPG, battery-free, persistent spinal pain syndrome, failed back surgery syndrome, low back pain, leg pain

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.

Does Temporary Externalization of Electrodes After Deep Brain Stimulation Surgery Result in a Higher Risk of Infection?

ObjectivesDeep brain stimulation (DBS) is a well-established surgical therapy for movement disorders that comprises implantation of stimulation electrodes and a pacemaker. These procedures can be performed separately, leaving the possibility of externalizing the electrodes for local field potential recording or testing multiple targets for therapeutic efficacy. It is still debated whether the temporary externalization of DBS electrodes leads to an increased risk of infection. We therefore aimed to assess the risk of infection during and after lead externalization in DBS surgery. Materials and MethodsIn this retrospective study, we analyzed a consecutive series of 624 DBS surgeries, including 266 instances with temporary externalization of DBS electrodes for a mean of 6.1 days. Patients were available for follow-up of at least one year, except in 15 instances. In 14 patients with negative test stimulation, electrodes were removed. All kinds of infections related to implantation of the neurostimulation system were accounted for. ResultsOverall, infections occurred in 22 of 624 surgeries (3.5%). Without externalization of electrodes, infections were noted after 7 of 358 surgeries (2.0%), whereas with externalization, 15 of 252 infections were found (6.0%). This difference was significant (p = 0.01), but it did not reach statistical significance when comparing groups within different diagnoses. The rate of infection with externalized electrodes was highest in psychiatric disorders (9.1%), followed by Parkinson’s disease (7.3%), pain (5.7%), and dystonia (5.5%). The duration of the externalization of the DBS electrodes was comparable in patients who developed an infection (6.1 ± 3.1 days) with duration in those who did not (6.0 ± 3.5 days). ConclusionsAlthough infection rates were relatively low in our study, there was a slightly higher infection rate when DBS electrodes were externalized. On the basis of our results, the indication for electrode externalization should be carefully considered, and patients should be informed about the possibility of a higher infection risk when externalization of DBS electrodes is planned.

An optimization framework for targeted spinal cord stimulation

Objective. Spinal cord stimulation (SCS) is a common neurostimulation therapy to manage chronic pain. Technological advances have produced new neurostimulation systems with expanded capabilities in an attempt to improve the clinical outcomes associated with SCS. However, these expanded capabilities have dramatically increased the number of possible stimulation parameters and made it intractable to efficiently explore this large parameter space within the context of standard clinical programming procedures. Therefore, in this study, we developed an optimization approach to define the optimal current amplitudes or fractions across individual contacts in an SCS electrode array(s). Approach. We developed an analytic method using the Lagrange multiplier method along with smoothing approximations. To test our optimization framework, we used a hybrid computational modeling approach that consisted of a finite element method model and multi-compartment models of axons and cells within the spinal cord. Moreover, we extended our approach to multi-objective optimization to explore the trade-off between activating regions of interest (ROIs) and regions of avoidance (ROAs). Main results. For simple ROIs, our framework suggested optimized configurations that resembled simple bipolar configurations. However, when we considered multi-objective optimization, our framework suggested nontrivial stimulation configurations that could be selected from Pareto fronts to target multiple ROIs or avoid ROAs. Significance. We developed an optimization framework for targeted SCS. Our method is analytic, which allows for the fast calculation of optimal solutions. For the first time, we provided a multi-objective approach for selective SCS. Through this approach, we were able to show that novel configurations can provide neural recruitment profiles that are not possible with conventional stimulation configurations (e.g. bipolar stimulation). Most importantly, once integrated with computational models that account for sources of interpatient variability (e.g. anatomy, electrode placement), our optimization framework can be utilized to provide stimulation settings tailored to the needs of individual patients.

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.