Neuromodulation Devices Research Articles

Development and Validation of an IoT Neurostimulator for the Treatment of Neurogenic Bladder.

Neurogenic bladder is a dysfunction in the lower urinary tract due to damage to the nervous system. One of the treatments that has shown important results is transcutaneous neuromodulation. The neuromodulation equipment available on the market does not allow remote activation or offer many resources for adjusting the parameters of the generated stimulus, as most devices operate with pre-established parameters in closed packages. For this reason, customizing therapy for each individual can be difficult. Therefore, the objective was to develop and validate a neuromodulation device capable of being remotely programmed and properly monitored. Materials and methods for validating devices were used according to the Brazilian Regulatory Standard (NBR), which deals with general requirements for the basic safety and essential performance of electromedical devices. After verifying the reliability of the device, which was capable of generating a biphasic and symmetrical wave, measured by an oscilloscope, considered safe by the technical requirements, it was tested in a real application. Users reported feeling a comfortable stimulus, similar to other previously used devices, and considered the device easy to use. In this way, it was possible to demonstrate the reliability and validity of the developed device.

Epilepsy: physiology, diseases, treatments, products, and market analysis

Epilepsy, a complex neurological disorder characterized by recurrent seizures, poses significant challenges to patients and healthcare providers alike.1 Pharmacotherapy remains a cornerstone of epilepsy treatment, and the paper explores the latest advancements in antiepileptic drugs (AEDs), highlighting novel agents and their mechanisms of action.2 Additionally, it discusses the challenges posed by drug-resistant epilepsy and explores alternative treatment options, such as neurostimulation and neuromodulation devices. Innovative techniques, such as deep brain stimulation (DBS) and vagus nerve stimulation (VNS) are reviewed in detail, emphasizing their potential as adjunctive therapies for seizure control. Surgical interventions, including resective surgery, laser interstitial thermal therapy (LITT), and functional hemispherectomy, are discussed as viable options for patients with medication-resistant epilepsy.3 This review aims to provide an encompassing exploration of types and characteristics of treatment products, and an in-depth analysis of the market, including market size, distribution, and current trends. Additionally, it will conclude by presenting an overview of emerging approaches in epilepsy treatment for potential clinical applications.

Selective recording of physiologically evoked neural activity in a mixed autonomic nerve using a minimally invasive array.

Real-time closed-loop control of neuromodulation devices requires long-term monitoring of neural activity in the peripheral nervous system. Although many signal extraction methods exist, few are both clinically viable and designed for extracting small signals from fragile peripheral visceral nerves. Here, we report that our minimally invasive recording and analysis technology extracts low to negative signal to noise ratio (SNR) neural activity from a visceral nerve with a high degree of specificity for fiber type and class. Complex activity was recorded from the rat pelvic nerve that was physiologically evoked during controlled bladder filling and voiding, in an extensively characterized in vivo model that provided an excellent test bed to validate our technology. Urethane-anesthetized male rats (n = 12) were implanted with a four-electrode planar array and the bladder instrumented for continuous-flow cystometry, which measures urodynamic function by recording bladder pressure changes during constant infusion of saline. We demonstrated that differential bipolar recordings and cross-correlation analyses extracts afferent and efferent activity, and discriminated between subpopulations of fibers based on conduction velocity. Integrated Aδ afferent fiber activity correlated with bladder pressure during voiding (r2: 0.66 ± 0.06) and was not affected by activating nociceptive afferents with intravesical capsaicin (r2: 0.59 ± 0.14, P = 0.54, and n = 3). Collectively, these results demonstrate our minimally invasive recording and analysis technology is selective in extracting mixed neural activity with low/negative SNR. Furthermore, integrated afferent activity reliably correlates with bladder pressure and is a promising first step in developing closed-loop technology for bladder control.

Vestibular Migraine Pathophysiology and Treatment: a Narrative Review.

To review the diagnosis of vestibular migraine (VM) and update the clinician on the most recent developments in our understanding of its pathophysiology and treatment. Functional imaging studies have identified multiple regions of the brain with abnormal activity and connectivity in VM. There is evidence of abnormal sensory processing and integration in VM patients. Calcitonin gene-related peptide (CGRP) has also been found to play a role in trigeminal and vestibular nucleus pathways. Research into treatment modalities has identified several neuromodulation devices that may be effective in VM. There are a growing number of evidence-based preventive options for VM, including medications that target CGRP. VM is best understood as a sensory processing disorder. CGRP appears to play a role, and further research is needed to fully understand its effects. Treatment options are expanding, but there is still a need for more randomly controlled trials in this area.

Navigating the FDA regulatory landscape.

Recent research and technological developments have led to an expanding number of novel and rapidly acting therapeutics being developed across a variety of neuropsychiatric disorders. Novel medical devices range from implantable and non-invasive brain stimulating and recording technologies to digital therapeutics. This perspective provides an overview of FDA regulatory oversight for medical devices, including a discussion of regulatory pathways and the review of neuromodulation devices for psychiatric disorders. We highlight the importance of early engagement with FDA and special programs that may be useful to device developers participating in interactions with the FDA that are solution focused. We explore current novel and rapid treatments for psychiatric disorders and those on the horizon. Lastly, we provide considerations for developers in navigating the regulatory landscape for neuromodulation devices intended for psychiatric disorders, including approaches to incorporating patient perspectives.

Innovations In Neuromodulation Techniques: A Comprehensive Review

Neurostimulation devices, also referred to as neuromodulation devices, have ushered in a transformative era in medical treatment by utilizing electrical impulses to activate specific nerves or brain regions. These devices hold significant promise as therapeutic interventions for a range of medical conditions, encompassing chronic pain, Parkinson's disease, epilepsy, depression, and more. This paper presents a comprehensive review of neurostimulation devices, encompassing their historical evolution, underlying mechanisms, and diverse applications are spanning various medical domains. In particular, the paper delves into the progress achieved in spinal cord stimulators, deep brain stimulators, Vagus nerve stimulators, peripheral nerve stimulators, and transcutaneous electrical nerve stimulators (TENS). The discussion encompasses their clinical efficacy, advantages, and constraints, while also addressing the safety and ethical considerations associated with their implantation.

Effects of Novel Dual Peripheral Nerve Stimulator Therapy: A Case Report

BACKGROUND: Peripheral nerve stimulators (PNS) are currently used for refractory cases of neuralgia, and are associated with single manufacturer use. This is the first case report describing the novel scenario where a patient received 2 neuromodulation devices from 2 different manufacturers. CASE REPORT: We present a 32-year-old woman with spinal muscle atrophy type 2 who received a permanent PNS implant for chronic neuralgia. She experienced gradual treatment failure over 6 months, but continued to have pain relief with subsequent nerve blocks to the same nerves. She underwent semipermanent PNS placement to those same nerves. After the semipermanent PNS was removed, she experienced new, unexpected symptoms after trying to use her permanent PNS again. CONCLUSION: Instances of multiple PNS treating the same area in patients is likely going to be a recurring scenario. More research will be needed to document the potential effects that dual neuromodulation therapy may have. KEY WORDS: Case report, chronic pain, dual therapy, peripheral nerve stimulator

Neuromodulation of the peripheral nervous system: Bioelectronic technology and prospective developments

AbstractThe peripheral nervous system (PNS) is a fascinatingly complex and crucial component of the human body, responsible for transmitting vital signals throughout the body's intricate network of nerves. Its efficient functioning is paramount to our health, with any dysfunction often resulting in serious medical conditions, including motor disorders, neurological diseases, and psychiatric disorders. Recent strides in science and technology have made neuromodulation of the PNS a promising avenue for addressing these health issues. Neuromodulation involves modifying nerve activity using a range of techniques, such as electrical, chemical, optical, and mechanical stimulation. Bioelectronics plays a critical role in this effort, allowing for precise, controlled, and sustained stimulation of the PNS. This paper provides an overview of the PNS, discusses the current state of neuromodulation devices, and presents emerging trends in the field, including advances in wireless power transfer and materials, that are shaping the future of neuromodulation.

Neuromodulation sacrée pour trouble de la vidange vésicale : expérience d’un centre universitaire français

To report the experience of a university hospital center with sacral neuromodulation for patients with bladder voiding disorders. All patients who underwent sacral neuromodulation between 1998 and 2022 for bladder voiding disorders were included. Medical records were analyzed retrospectively, and population, efficacy and follow-up data were collected. A total of 134 patients underwent test implantation and 122 patients were analyzed. 68 patients (56%) were implanted with a definitive neuromodulation device. Mean age was 43±16 years and BMI 25.5±5.4kg/m2. 74% were women. Bladder voiding disorder was due to sphincter hypertonia in 51% of cases, with associated bladder hypocontractility in 29%. The spontaneous micturition rate after implantation increased from 34% to 92%. Implantation results appeared to be better in patients with sphincter hypertonia, whether or not associated with bladder hypocontractility. The benefit was most often present with a frequency of 5Hz (54.4%). Side-effects were present in 52% of cases at 5 years, and in 85% of cases were pain in relation to the implanted devices. They resolved under medical treatment or after revision of the device (27% of cases at 5 years). SNM is effective in micturition recovery, but has side effects. Urodynamic mechanism and etiology may provide clues for modulating NMS box settings and determining predictive factors for NMS success. Data from other centers are needed to identify reliable predictive factors.

Knowledge and Perception Toward Neuromodulation Devices Among Medical Students at Umm Al-Qura University.

Introduction Neurologic and psychiatric disorders affect many people worldwide and are crucial to medical care. It is crucial to note that primary care doctors initially evaluate patients who will eventually require neuromodulation (NM) therapy. There is a growing concern about the extent of medical students' knowledge regarding NM therapy. Insufficient education and limited exposure of future doctors to different treatment approaches can limit their ability to refer patients promptly and appropriately, thereby impeding access to necessary treatment. Methods The study employed a non-probability stratified snowball sampling technique to recruit participants. The population consisted of undergraduate medical students (excluding interns) at Umm Al-Qura University (UQU) in Saudi Arabia. Data collection was conducted through an online questionnaire. Results The sample comprised 301 medical students, with an average age of 21.62±1.54 years (ranging from 18 to 25). The majority were female (65.1%), and in the clinical years (57.8%), a considerable portion of respondents (57.5%) lacked awareness that NM devices are approved by the FDA for treatment. Both pre-clinical and clinical-year students exhibited insufficient knowledge (91.3% and 91.4%, respectively). Females showed a higher proportion (95.9%) of poor attitudes toward NM compared to males (83.8%). Notably, preclinical students showed a higher level of knowledge (11.0%) compared to clinical students (6.3%). Conclusions The study revealed a significant lack of knowledge among medical students regarding NM devices. This is concerning given the growing prevalence of NM devices in clinical practice. To ensure optimal patient care, it is crucial to provide comprehensive education on NM devices to medical students.

Closing the loop and raising the bar: Automated control systems in neuromodulation.

Neuromodulation has emerged as a promising therapy for the management of chronic pain, movement disorders, and other neurological conditions. Spinal cord stimulation (SCS) is a widely used form of neuromodulation that involves the delivery of electrical impulses to the spinal cord to modulate the transmission of pain signals to the brain. In recent years, there has been increasing interest in the use of automation systems to improve the efficacy and safety of SCS. This narrative review summarizes the status of Food and Drug Administration-approved autonomous neuromodulation devices including closed loop, feedforward, and feedback systems. The review discusses the advantages and disadvantages of each system and focuses specifically on the use of these systems for SCS. It is important for clinicians to understand the expanding role of automation in neuromodulation in order to select appropriate therapies founded on automation systems to the specific needs of the patient and the underlying condition. The review also provides insights into the current state of the art in neuromodulation automation systems and discusses potential future directions for research in this field.

Rationale and design of an implant procedure and pivotal study to evaluate safety and effectiveness of Medtronic's tibial neuromodulation device

Percutaneous tibial neuromodulation is a medical guideline recommended therapy for treating symptoms of overactive bladder. Stimulation is delivered to the tibial nerve via a thin needle placed percutaneously for 30 min once a week for 12-weeks, and monthly thereafter. Studies have shown that this therapy can effectively relieve symptoms of overactive bladder; however, the frequent office visits present a barrier to patients and can impact therapy effectiveness. To mitigate the burden of frequent clinic visits, small implantable devices are being developed to deliver tibial neuromodulation. These devices are implanted during a single minimally invasive procedure and deliver stimulation intermittently, similar to percutaneous tibial neuromodulation. Here, we describe the implant procedure and design of a pivotal study evaluating the safety and effectiveness for an implantable tibial neuromodulation device. The Evaluation of Implantable Tibial Neuromodulation (TITAN 2) pivotal study is a prospective, multicenter, investigational device exemption study being conducted at up to 30 sites in the United States and enrolling subjects with symptoms of overactive bladder.

Understanding a decade of safety reporting for sacral neuromodulation in the Food and Drug Administration Manufacturer and User Facility Device Experience database.

Over 350 000 sacral neuromodulation (SNM) devices have been implanted since approval by the Food and Drug Administration (FDA) in 1998. SNM technology and clinical applications have evolved, with minimal safety updates after initial trials. We aim to provide an updated overview of real-world SNM safety. These insights will guide informed consent, preoperative counseling, and patient expectation-setting. The FDA Manufacturer and User Facility Device Experience (MAUDE) database is a repository for medical device safety reports. We performed MAUDE categorical (1/1/98-12/31/10) and keyword (1/1/11-9/30/21) searches for "Interstim." A random sample of 1000 reports was reviewed and categorized by theme. To corroborate our MAUDE database analysis, a legal librarian searched the Public Access to Court Electronic Records (PACER) database, as well as Bloomberg Law's dockets database for all lawsuits related to SNM devices. Our search of the MAUDE database returned 44 122 SNM-related adverse events (AEs). The figure illustrates the prevalence of event categories in the random sample. The largest proportion of reports (25.6%) related to a patient's need for assistance with device use, followed by loss/change of efficacy (19.0%). Interestingly, a fall preceded issue onset in 32% of non-shock pain, 30% of lead/device migration, and 27% of painful shock reports. Our legal search revealed only four lawsuits: one for patient complications after an SNM device was used off-label, one case of transverse myelitis after implant, one for device migration or poor placement, and the fourth claimed the device malfunctioned requiring removal and causing permanent injury. This review confirms the real-world safety of SNM devices and very low complication rates as seen in the original clinical trials. Our findings indicate that 43.2% (95% confidence interval 40.1%-46.3%) of SNM "complications" are not AEs, per se, but rather reflect a need for improved technical support or more comprehensive informed consent to convey known device limitations to the patient, such as battery life. Similarly, the number of lawsuits is shockingly low for a device that has been in the market for 24 years, reinforcing the safety of the device. Legal cases involving SNM devices seem to relate to inappropriate patient selection-including at least one case in which SNM was used for a non-FDA approved indication-lack of appropriate follow-up, and/or provider inability to assist the patient with utilizing the device after implantation.

Denoising and decoding spontaneous vagus nerve recordings with machine learning.

Neural interfaces that electrically stimulate the peripheral nervous system have been shown to successfully improve symptom management for several conditions, such as epilepsy and depression. A crucial part for closing the loop and improving the efficacy of implantable neuromodulation devices is the efficient extraction of meaningful information from nerve recordings, which can have a low Signal-to-Noise ratio (SNR) and non-stationary noise. In recent years, machine learning (ML) models have shown outstanding performance in regression and classification problems, but it is often unclear how to translate and assess these for novel tasks in biomedical engineering. This paper aims to adapt existing ML algorithms to carry out unsupervised denoising of neural recordings instead. This is achieved by applying bandpass filtering and two novel ML algorithms to in-vivo spontaneous, low-SNR vagus nerve recordings. The performance of each approach is compared using the task of extracting respiratory afferent activity and validated using cross-correlation, MSE, and accuracy in terms of extracting the true respiratory rate. A variational autoencoder (VAE) model in particular produces results that show better correlation with respiratory activity compared to bandpass filtering, highlighting that these models have the potential to preserve relevant features in complex neural recordings.

ID: 216731 A Comparison of Neuromodulation Devices in the Setting of Various Primary Headache Disorders

Primary headache disorders are among the most common central nervous system disorders accounting for 98% of all headaches. There exists a large unmet need for non-invasive non-pharmacological treatments for patients who have contraindications to or have failed standard therapy. Over the past two decades non-invasive neuromodulation devices with varying mechanisms have been developed to address this need, but little information is available comparing wearable therapeutic regimens. As such, we sought to explore the current landscape of FDA-approved or FDA-cleared neuromodulation devices.

ID: 214173 Evaluating Physician Understanding of Data Privacy and Cybersecurity in Neuromodulation Systems

Advances in Implantable Medical Devices (IMDs) with wireless communication features have provided healthcare providers with new capabilities, such as remote device programming and patient monitoring.[1] Unfortunately, reliance on software and networks for wireless communication with IMDs allows for vulnerabilities to outside attack. Patients with neuromodulation devices represent a unique group of potential targets to hackers because of the data points these devices collect and can transmit. Healthcare providers bear the responsibility of educating patients on the data privacy and cybersecurity risks involved with IMDs. Little research has been done to learn what practicing physicians understand about these issues. We seek to investigate healthcare provider knowledge of neuromodulation device cybersecurity and data privacy using survey data analysis.

RWD34 Comparison of Implant Surgery and Readmissions Costs for DBS and VNS

Epilepsy affects all ages and is a common, disabling serious neurological disease often associated with comorbidities. The disease presents a heavy clinical, economic, and societal burden with a continued treatment gap that deserves the attention of healthcare decision-makers. A considerable number of patients do not respond satisfactorily to drug treatment and/or are ineligible for resective epilepsy surgery. Implant surgery offers a therapeutic option for these patients. Deep Brain Stimulation (DBS) and Vagus Nerve Stimulation (VNS) are neuromodulation devices that intervene directly in neural circuits and present interesting clinical results in seizure control.

P.098 Antibacterial envelopes prevent post-operative infections in neuromodulation surgery

Background: Neuromodulation unit placement can provide efficacious control of many neurological conditions. They are high risk for infection with a historic infection rate as high as 10%. Treatment of infection requires surgical removal and a long course of systemic antibiotics. <font size=”1”> </font>At our center, one surgeon uses antibacterial envelopes with all implanted neuromodulation devices. Methods: We conducted a retrospective cohort study of consecutive implantable pulse generator (IPG) and intrathecal pump unit implantation with an antibacterial envelope at our center. This cohort was then compared to a historical cohort of consecutive patients undergoing IPG or pump placement or revision prior to the use of the envelopes. Results: IPG: There were 18 (11.9%) class I infections in the pre-envelope cohort compared with 5 (2.1%) in the post-envelope cohort. The absolute risk reduction (ARR) with the use of antibacterial envelopes was 9.85% (95% confidence interval (CI) 4.3-15.4%, p<0.01).Pump: There were 6 (14.6%) class I infections in the pre-envelope cohort compared with 1 (1.7%) in the post-envelope cohort. The ARR with the use of antibacterial envelopes was 12.9% (95% confidence interval 1.6-24.3, p<0.05). Conclusions: Based on our results, we recommend usage of antibacterial envelopes to reduce infection rates in neuromodulation surgery. Further study is needed.

ID: 212903 An Injectable Wire Mesh Electrode (BASMATI Injectrode) Enables Minimally Invasive Stimulation Therapy in Clinical Trial

Individuals suffering from chronic pain undergo surgical procedures to receive neuromodulation devices, often requiring revision surgery to replace an exhausted battery with a new device. There is a need to eliminate revision surgery with a minimally invasive device. The Injectrode is an injectable electrode designed for rapid placement and removal by a minimally invasive procedure. Here we present data from a non-significant risk clinical trial to assess the safety and function of the Injectrode via a subcutaneously placed gold mesh (BASMATI Injectrode) for 28 days.

Perioperative and anesthetic considerations for the management of neuromodulation systems

The use of neuromodulation systems is increasing for the treatment of various pathologies ranging from movement disorders to urinary incontinence to chronic pain syndromes. While the type of neuromodulation devices...