Neuromodulation Devices Research Articles

O122 / #676 VAGUS NERVE STIMULATION TO TREAT RHEUMATOID ARTHRITIS: RATIONALE, OBJECTIVES AND DESIGN OF THE RESET-RA STUDY: TRACK 3: VAGUS NERVE STIMULATION / TOOLS TO INFORM PATIENT CARE

The inflammatory reflex is a centrally integrated physiological mechanism in which signaling through the vagus nerve regulates cytokine production and peripheral inflammation1. Results from a previously reported first-in-human study showed that vagus nerve stimulation (VNS), using a neuromodulation device platform comprising a novel, miniaturized, integrated neurostimulator, improved clinical outcomes and was safe and well-tolerated in patients with multidrug-refractory disease2. Based upon these findings, a pivotal study has been initiated to further evaluate VNS for the treatment of rheumatoid arthritis (RA).

Use of Antibacterial Envelopes for Prevention of Infection in Neuromodulation Implantable Pulse Generators.

Neuromodulation unit placement carries a historic infection rate as high as 12%. Treatment of such requires surgical removal and a long course of systemic antibiotics. Antibiotic-impregnated envelopes have been effective in preventing infection in implantable cardiac devices. At our center, 1 surgeon uses these envelopes with all implanted neuromodulation units. To assess the efficacy of antibacterial envelopes in prevention of infection in neuromodulation device placement. We conducted a retrospective cohort study of consecutive implantable pulse generator (IPG) unit implantation with an antibacterial envelope at a single center between October 2014 and December 2019. We collected demographic data, including postoperative infections, reoperations, and complications, associated with the IPGs. This cohort was then compared with a historical cohort of consecutive patients undergoing surgery before envelope usage (October 2007-April 2014). In the pre-envelope cohort of 151 IPGs placed in 116 patients, there were 18 culture-confirmed infections (11.9%). In the antibacterial envelope cohort of 233 IPGs placed in 185 patients, there were 5 culture-confirmed infections (2.1%). The absolute risk reduction of the antibacterial envelope was 9.85% (95% CI 4.3%-15.4%, P < .01). The number needed to treat was 10.1 (95% CI 6.5-23.1, P < .01) envelopes to prevent 1 IPG infection. We saw a reduced rate of infections in the antibacterial envelope cohort. Although this is likely multifactorial, our results suggest a benefit of antibacterial envelopes on infection after neuromodulation surgery.

Goals, Expectations, and the Definition of Success for Neuromodulation for Pain According to Representatives of Neuromodulation Device Manufacturers.

Representatives of neuromodulation device manufacturers are expected to facilitate the relationship between patients and healthcare providers. Nevertheless, the goals, expectations, and definition of success for neuromodulation for pain have not yet been explored. Representatives present at the 2nd Joint Congress of the INS European Chapters in September 2021 completed a survey to ascertain their opinions about the goals to achieve with neuromodulation, the factors that they expect to change, and their definition of success for neuromodulation. In total, 39 representatives completed the survey. To provide excellent service for patients (22.4%), to become a trusted partner for physicians (21.5%), and to provide excellent service for physicians (20.7%) were the highest ranked goals. The most frequently reported factors that were expected to change were pain intensity (23.1%), patient satisfaction (19.7%), mobility/functioning (14.5%), and capacity to return to work (13.7%). Within the definitions of success, increased quality of life of the patient was stated in 21% of the definitions, closely followed by pain control (19.3%) and happiness/patient satisfaction (15.8%). The goals of representatives of neuromodulation device manufacturers seem to focus on ensuring a good relationship with physicians on the one hand and providing good service towards patients on the other hand, whereby pain control, quality of life, and patient satisfaction seem to be important for company representatives.

Vaginal Lubrication and Pressure Increase Induced by Pudendal Nerve Stimulation in Cats

Vaginal lubrication and contractions are among the top difficulties affecting sexual intercourse in women after spinal cord injury. This study aimed at determining if pudendal nerve stimulation (PNS) can improve vaginal lubrication and induce increases in vaginal pressure. In anesthetized cats, a small piece of cotton was inserted into the vagina for 10 minutes with or without PNS to measure vaginal wetness by the weight increase of the vaginal cotton. Then, a small balloon catheter was inserted into the vagina to measure the pressure increase induced by PNS. Intensity response of the vagina to PNS (30 Hz, 0.2 ms, 5 seconds) was determined at 1-4 times of intensity threshold (T) for PNS to induce an observable vaginal pressure increase. Frequency response was determined at 2T intensity in a range of PNS frequencies (5-50 Hz). Finally, fatigue in vaginal pressure was determined by applying PNS (30 Hz, 2T) either continuously or intermittently (5 seconds on and 5 seconds off) for 4 minutes. The effectiveness of PNS in increasing vaginal wetness and pressure is evaluated. PNS significantly (P=.0327) increased the measurement of vaginal wetness from 15.8 ± 3.8 mg during control without stimulation to 32.4 ± 4.7 mg after stimulation. Vaginal pressure increased as PNS intensity or frequency increased. PNS (30 Hz, 2T) induced vaginal pressure increase ≥80% of the maximal response. Intermittent PNS induced significantly (P=.0354) smaller fatigue (45.6 ± 3.7%) in vaginal pressure than continuous PNS (69.1 ± 3.0%) during the 4-minute stimulation. This study raises the possibility of developing a novel pudendal neuromodulation device to improve female sexual function after spinal cord injury. This study provides preclinical data supporting the development of a novel pudendal neuromodulation device. The limitation includes the lack of chemical analysis of the vaginal secretion. PNS can improve vaginal lubrication and induce increases in vaginal pressure. Chen J, Zhong Y, Wang J, et al. Vaginal Lubrication and Pressure Increase Induced by Pudendal Nerve Stimulation in Cats. J Sex Med 2022;19:1517-1523.

A system of real-time neural recording and stimulation and its potential application in blood pressure modulation.

Hypertension is one of the most prevalent chronic diseases that affects more than 20% of the adult population worldwide, but fortunately, most of their blood pressure can be effectively controlled via drug treatment. However, there still remains 5–30% of patients clinically who do not respond well to conventional medication, while the non-drug treatments currently existing are struggling with major drawbacks like irreversible nerve damage, huge side effects, and even non-effectiveness. In this study, based on the physiological regulation mechanism of blood pressure and state-of-the-art neuromodulation technique, we worked along with the vagus nerve stimulation scheme, developed, and explored whether and how a real-time neural recording and stimulation system could provide an insight into self-adaptive modulation in the blood pressure, in the hope to crack a crevice in the closed-loop treatment for resistant hypertension. Unlike traditional neuromodulation devices, additional signal recording and real-time wireless transmission functions are added to the same device to realize the features of a dynamic monitor and modulator. The system is tested both in vitro and in vivo, showing decent electrical performance of 8 kHz sampling rate and flexible stimulation outputs which sufficiently covers our needs in manipulating neural activities of interest. A relatively stable drop in the blood pressure resulting from stimulation was observed and specific patterns in the vagus nerve signals relating to blood pressure could also be primarily identified. This laid a solid foundation for further studies on the final realization of closed-loop automatic adjustment for resistive hypertension treatment.

Prevention and Management Strategies for Diabetic Neuropathy.

Diabetic neuropathy (DN) is a common complication of diabetes that is becoming an increasing concern as the prevalence of diabetes rapidly rises. There are several types of DN, but the most prevalent and studied type is distal symmetrical polyneuropathy, which is the focus of this review and is simply referred to as DN. It can lead to a wide range of sensorimotor and psychosocial symptoms and is a major risk factor for diabetic foot ulceration and Charcot neuropathic osteoarthropathy, which are associated with high rates of lower limb amputation and mortality. The prevention and management of DN are thus critical, and clinical guidelines recommend several strategies for these based on the best available evidence. This article aims to provide a narrative review of DN prevention and management strategies by discussing these guidelines and the evidence that supports them. First, the epidemiology and diverse clinical manifestations of DN are summarized. Then, prevention strategies such as glycemic control, lifestyle modifications and footcare are discussed, as well as the importance of early diagnosis. Finally, neuropathic pain management strategies and promising novel therapies under investigation such as neuromodulation devices and nutraceuticals are reviewed.

ID:16157 Spinal Cord Stimulation and MRI Compatibility Issue: Calling for Silicon Valley Approach for MRI Safety

Chronic pain is a worldwide problem, often nonresponsive to pharmaceutical therapies, but many patients respond well to neuromodulation therapy. The components of this whole device have ferromagnetic potential which means that the device not only can cause artifacts on imaging but may prevent patients from getting MRI and thus delaying diagnostic workup. The problem is compounded by the fact that utilizing devices or leads from various manufactures affect MRI compatibility. We report a case in which the presence of the neuromodulation device prevented a patient from getting an MRI, thereby complicating the task of completing a workup in the presence of new onset neurological deficit.

ID:16336 Device Explant Disposition: An Institute of Neuromodulation Survey

In 1996 the FDA published Medical Device Reporting for Facilities. This report provided guidance on the disposition of explanted devices for facilities. In 2019 the Institute of Neuromodulation (ION) Committee on Device Disposition convened a meeting to investigate if these guidelines were being routinely implemented in clinical practice. To better understand the prevalence of adoption of these guidelines, an IRB-approved survey was emailed to all NANS members asking how their individual facilities processed explanted neuromodulation devices.

Imaging peripheral nerve micro-anatomy with MUSE, 2D and 3D approaches

Understanding peripheral nerve micro-anatomy can assist in the development of safe and effective neuromodulation devices. However, current approaches for imaging nerve morphology at the fiber level are either cumbersome, require substantial instrumentation, have a limited volume of view, or are limited in resolution/contrast. We present alternative methods based on MUSE (Microscopy with Ultraviolet Surface Excitation) imaging to investigate peripheral nerve morphology, both in 2D and 3D. For 2D imaging, fixed samples are imaged on a conventional MUSE system either label free (via auto-fluorescence) or after staining with fluorescent dyes. This method provides a simple and rapid technique to visualize myelinated nerve fibers at specific locations along the length of the nerve and perform measurements of fiber morphology (e.g., axon diameter and g-ratio). For 3D imaging, a whole-mount staining and MUSE block-face imaging method is developed that can be used to characterize peripheral nerve micro-anatomy and improve the accuracy of computational models in neuromodulation. Images of rat sciatic and human cadaver tibial nerves are presented, illustrating the applicability of the method in different preclinical models.

ID:16073 A Review of the Factors and Outcomes of Institutional Interdisciplinary Neuromodulation Committees: A Multi-Center Experience

The concept of a Neuromodulation Committee was created to enact a collaborative and interdisciplinary approach to neuromodulation. The process has been implemented at the University of California, Davis (UCD) and Stanford University. The committee is composed of implanters, a pain psychologist who completes all pre-procedural psychological assessments, a nurse practitioner or physician assistant who sees patients for preoperative history and physicals, and current pain fellows. The goals of the committee are to weigh the risks and benefits of the neuromodulation device, approach, and patient candidacy.

Memristor-Based Neuromodulation Device for Real-Time Monitoring and Adaptive Control of Neuronal Populations.

Neurons are specialized cells for information transmission and information processing. In fact, many neurologic disorders are directly linked not to cellular viability/homeostasis issues but rather to specific anomalies in electrical activity dynamics. Consequently, therapeutic strategies based on the direct modulation of neuronal electrical activity have been producing remarkable results, with successful examples ranging from cochlear implants to deep brain stimulation. Developments in these implantable devices are hindered, however, by important challenges such as power requirements, size factor, signal transduction, and adaptability/computational capabilities. Memristors, neuromorphic nanoscale electronic components able to emulate natural synapses, provide unique properties to address these constraints, and their use in neuroprosthetic devices is being actively explored. Here, we demonstrate, for the first time, the use of memristive devices in a clinically relevant setting where communication between two neuronal populations is conditioned to specific activity patterns in the source population. In our approach, the memristor device performs a pattern detection computation and acts as an artificial synapse capable of reversible short-term plasticity. Using in vitro hippocampal neuronal cultures, we show real-time adaptive control with a high degree of reproducibility using our monitor-compute-actuate paradigm. We envision very similar systems being used for the automatic detection and suppression of seizures in epileptic patients.

Auditory independent low-intensity ultrasound stimulation of mouse brain is associated with neuronal ERK phosphorylation and an increase of Tbr2 marked neuroprogenitors

Transcranial ultrasound stimulation is an emerging technique for the development of a non-invasive neuromodulation device for the treatment of various types of neurodegenerations and brain damages. However, there are very few studies that have quantified the optimal ultrasound dosage and the long-term associated effects of transcranial ultrasound treatments of brain diseases. In this study, we used a simple ex vivo hippocampal tissues stimulated by different dosages of ultrasound in combination with different chemical treatments to quantify the required energy for a measurable effect. After determining the most desirable ex vivo stimulation conditions, it was then replicated for the in vivo mouse brains. It was discovered that transcranial ultrasound promoted the increase of Tbr2-expressing neural progenitors in an ASIC1a-dependent manner. Furthermore, such effect was observable at least a week after the initial ultrasound treatments and was not abolished by auditory toxicity.

Six-Month Outcomes of Reimplantation of a Coin-Sized Tibial Nerve Stimulator for the Treatment of Overactive Bladder Syndrome With Urgency Urinary Incontinence.

ObjectiveThe eCoin (Valencia Technologies Corporation, Valencia, CA) is a battery-powered, nickel-sized and shaped neuromodulation device for the treatment of overactive bladder, and it is implanted in the lower leg in a short office or outpatient procedure under local anesthesia. A follow-on trial was conducted to evaluate the feasibility, safety, and efficacy of eCoin reimplantation.MethodsThis was a prospective, single-arm, open-label study, including 23 participants with refractory urgency urinary incontinence (UUI) who were previously participants in the eCoin clinical feasibility trial. This follow-on study was conducted at 7 sites in the United States and New Zealand. Participants were reimplanted with a new eCoin device and activated after 4 weeks. Bladder diary data and validated quality-of-life instruments, collected at 12 weeks and 24 weeks postactivation, were compared with baseline.ResultsParticipants of the study were considered responders if they reported a ≥ 50% reduction from baseline in episodes of UUI on a 3-day voiding diary. At 12 weeks of treatment, 74% (95% confidence interval [CI], 52%–90%) of participants were considered responders. At 24 weeks of treatment, 82% (95% CI, 60%–95%) of participants were considered responders with 36% (95% CI, 20%–57%) of participants achieving complete continence. There were no device-related serious adverse events reported during the study.ConclusionsThe reimplantation of eCoin was both safe and effective in treating UUI associated with overactive bladder syndrome. The demonstrated significant reduction or resolution of symptoms with no serious safety concern suggests that eCoin is a convenient and maintainable therapeutic device.

387 Clinical characteristics and psychosocial factors associated with temporary neuromodulation success

OBJECTIVES/GOALS: The present work aims to use baseline data to identify demographic, clinical, and psychosocial factors associated with patients who receive analgesic benefit from temporary neurostimulation. METHODS/STUDY POPULATION: This study presents baseline data from our descriptive, prospective, longitudinal study. Consecutive patients who present to the University of Arkansas for Medical Sciences Interventional Pain Management Clinic for implantation of a neurostimulation device, have met clinical criteria for implantation of a neuromodulation device, and are able to speak and understand English are invited to participate. Prior to the placement of the temporary stimulator, each patient completes demographic and symptom-related questionnaires. Clinical characteristics are obtained through medical record review. RESULTS/ANTICIPATED RESULTS: We anticipate enrolling 50 participants in order to have 30 patients that report analgesic benefit from temporary neurostimulation. Variability in demographics, clinical characteristics, and psychosocial factors will be reported between patients who receive and those who do not receive analgesia following temporary neurostimulation. Gender differences will also be reported. DISCUSSION/SIGNIFICANCE: Despite the use of varying outcome measures, studies to date have not incorporated validated patient reported outcomes or controlled for key demographic and clinical characteristics. Our analysis evaluates clinical and psychosocial variables associated with successful temporary neurostimulation.

New Product Launches, Approvals, And Acquisitions to Expand Pain Management Devices Portfolio Worldwide

Advancements in technology and the approach of innovation by healthcare companies led to considerable improvements in pain management devices over the past years. From management of chronic pain to reliving post-operative pain, innovative devices have been making their way into the world. Leading device manufacturers have been developing and launching their new products that would relive and manage different kinds of pain. From knee braces to cap-sized neuromodulation devices, new products have been launched to help people improve the quality of their lives. Some of the products are in the development stage, while some have been commercialized and launched. The trend of innovation is expected to bring breakthrough devices in the coming years.

Micropyramid structured photo capacitive interfaces

Optically driven electronic neuromodulation devices are a novel tool in basic research and offer new prospects in medical therapeutic applications. Optimal operation of such devices requires efficient light capture and charge generation, effective electrical communication across the device’s bioelectronic interface, conformal adhesion to the target tissue, and mechanical stability of the device during the lifetime of the implant—all of which can be tuned by spatial structuring of the device. We demonstrate a 3D structured opto-bioelectronic device—an organic electrolytic photocapacitor spatially designed by depositing the active device layers on an inverted micropyramid-shaped substrate. Ultrathin, transparent, and flexible micropyramid-shaped foil was fabricated by chemical vapour deposition of parylene C on silicon moulds containing arrays of inverted micropyramids, followed by a peel-off procedure. The capacitive current delivered by the devices showed a strong dependency on the underlying spatial structure. The device performance was evaluated by numerical modelling. We propose that the developed numerical model can be used as a basis for the design of future functional 3D design of opto-bioelectronic devices and electrodes.

127 Accessibility and Ease of Use in Neuromodulation Devices

INTRODUCTION: Inclusive design is an engineering process that requires the product development team to balance the needs and limitations of many stakeholders, including those of the end user, regulatory organizations, and the designing institution. However, some patients confront challenges in using neuromodulation devices. These challenges include visual or hearing impairment and mobility and dexterity limitations that affect operation of the device components. METHODS: A primary set of points based on the seven principles of universal design, Twenty-First Century Communications and Video Accessibility Act (CVAA), Section 508, Web Content Accessibility Guidelines (WCAG), and the Americans with Disabilities Act (ADA) were created to obtain ratings of neuromodulation device characteristics for accessible operation. The author team developed a list of FDA-approved devices for brain, spinal, and peripheral pain neuromodulation available in the United States in 2021 and a standard survey was administered to evaluate each component. Data were gathered from representative patient-operated components of neuromodulation systems including device controllers and chargers to compare and rank the inclusivity of each. RESULTS: A representative number of neuromodulation devices in each category were assessed. Current data show multiple areas to improve the inclusivity of these devices. Multiple disabilities are not adequately considered during design. Inclusivity scores for the considered disabilities are summarized. CONCLUSION: Many currently FDA-approved neuromodulation devices are limited in their utility for disabled patients. Incorporating the recommendations of universal design into future devices will increase quality of care for our diverse and aging population.

Datafied Brains and Digital Twins: Lessons From Industry, Caution For Psychiatry

This paper asks what sorts of ethical caution ought to attach to increasingly data-driven approaches to understanding the brain. This is taken to be an important question especially owing to a likely near future of neuromonitoring and neuromodulation devices with applications in psychiatry. The paper explores this by i) sketching the concept of ‘digital twin,’ ii) drawing a schematic picture of ‘brain datafication’ in general, and iii) developing a means of understanding some challenges present in datafication through the lens of digital twins. One central concern arises from the role algorithmic processing of neural recordings plays in terms of neuroscientific objectivity, with knock on effects for psychiatric ethics. Essentially, this is owing to a way in which algorithmic processing in brain data construction appears to be deductive in character, but is in fact based on a particular scheme of inductive inference. The challenges explored urge ethical caution as they concern epistemological gaps in data-centered neuroscientific progress, as well as knock-on effects for psychiatry.

Essential components of care in a multidisciplinary headache center: Perspectives from headache neurology specialists.

Comprehensive headache care involves numerous specialties and components that have not been well documented or standardized. This study aimed to elicit best practices and characterize important elements of care to be provided in multidisciplinary headache centers. Qualitative, semi-structured telephone interviews with a purposive sample of headache neurology specialists from across the US, using open-ended questions. Interviews were recorded, transcribed, and coded. Coded data were further analyzed using immersion/crystallization techniques for final interpretation. Mean years providing headache care was 17.7 (SD=10.6). Twelve of the 13 participants held United Council for Neurologic Subspecialties headache certification. Six described their practice site as providing multidisciplinary headache care. Participants explained most of their patients had seen multiple doctors over many years, and had tried numerous unsuccessful treatments. They noted patients with chronic headache frequently present with comorbidities and become stigmatized. All participants asserted successful care depends on taking time to talk with and listen to patients, gain understanding, and earn trust. All participants believed multidisciplinary care is essential within a comprehensive headache center, along with staffing enough headache specialists, implementing detailed headache intake and follow-up protocols, and providing the newest medications, neuromodulation devices, botulinum toxin injections, monoclonal antibodies, nerve blocks and infusions, and treatment from a health psychologist. Other essential services for a headache center are other behavioral health practitioners providing cognitive behavioral therapy, mindfulness, biofeedback and pain management; and autonomic neurology, neuropsychology, vestibular audiology, sleep medicine, physical therapy, occupational therapy, exercise physiology, speech therapy, nutrition, complementary integrative health modalities, and highly trained support staff. While headache neurology specialists form the backbone of headache care, experts interviewed for this study maintained their specialty is just one of many types of care needed to adequately treat patients with chronic headache, and this is best provided in a comprehensive, multidisciplinary center.

Time-Series Generative Adversarial Network Approach of Deep Learning Improves Seizure Detection From the Human Thalamic SEEG.

Seizure detection algorithms are often optimized to detect seizures from the epileptogenic cortex. However, in non-localizable epilepsies, the thalamus is frequently targeted for neuromodulation. Developing a reliable seizure detection algorithm from thalamic SEEG may facilitate the translation of closed-loop neuromodulation. Deep learning algorithms promise reliable seizure detectors, but the major impediment is the lack of larger samples of curated ictal thalamic SEEG needed for training classifiers. We aimed to investigate if synthetic data generated by temporal Generative Adversarial Networks (TGAN) can inflate the sample size to improve the performance of a deep learning classifier of ictal and interictal states from limited samples of thalamic SEEG. Thalamic SEEG from 13 patients (84 seizures) was obtained during stereo EEG evaluation for epilepsy surgery. Overall, TGAN generated synthetic data augmented the performance of the bidirectional Long-Short Term Memory (BiLSTM) performance in classifying thalamic ictal and baseline states. Adding synthetic data improved the accuracy of the detection model by 18.5%. Importantly, this approach can be applied to classify electrographic seizure onset patterns or develop patient-specific seizure detectors from implanted neuromodulation devices.