Wireless and Catheter-Free Bladder Pressure and Volume Sensor.

Continuous monitoring of bladder activity during normal daily activities would improve clinical diagnostics and understanding of the mechanisms underlying bladder function, or help validate how differing neuromodulation strategies affect the bladder. This work describes a urological monitor of conscious activity (UroMOCA). The UroMOCA included a pressure sensor, urine impedance-sensing electrodes, and wireless battery recharge and data transmission circuitry. Components were assembled on a circuit board and encapsulated with an epoxy/silicone molded package that allowed Pt-Ir electrode feedthrough for urine contact. Packaged UroMOCAs measured 12 × 18 × 6 mm. UroMOCAs continuously transmitted data from all onboard sensors at 10 Hz at 30 cm range, and ran for up to 44 hours between wireless recharges. After in vitro calibration, implantations were performed in 11 animals. Animals carried the device for 28 days, enabling many observations of bladder behavior during natural, conscious behavior. In vivo testing confirmed the UroMOCA did not impact bladder function after a two-week healing period. Pressure data in vivo were highly correlated to a reference catheter used during an anesthetized follow-up. Static volume sensor data were less accurate, but demonstrated reliable detection of bladder volume decreases, and distinguished between voiding and non-voiding bladder events.

Priorities, needs and willingness of use of nerve stimulation devices for bladder and bowel function in people with spinal cord injury (SCI): an Australian survey.

STUDY DESIGN: Anonymous online survey OBJECTIVES: To investigate the priorities, needs and willingness to adopt nerve stimulation devices for managing neurogenic bladder and bowel function in people with spinal cord injury (SCI) living in Australia. SETTING: Online survey of people living with SCI in Australia. METHODS: This anonymous online survey used Qualtrics and was advertised via standard communication channels, such as advocacy groups representing the SCI community in Australia, social media, attending SCI sporting events and by word-of-mouth. RESULTS: Responses from 62 individuals (32% female, 68% male) were included. Bladder emptying through urethra without catheter was the highest priority for bladder function. Reducing time required for bowel routines and constipation were the top priorities regarding bowel function. The highest concern for internal/implanted devices was the 4% chance of device surgical removal, while wearing wires under the clothes was the main concern for external devices. 53% of respondents were willing to trial an implanted nerve stimulation device, while 70% would trial an external device to improve and gain independence in bladder and bowel function. CONCLUSION: The findings of this study highlighted the potential role in which nerve stimulation can have in addressing bladder and bowel dysfunction in people with SCI, and have also identified that there was a need for Australian physiotherapists to evaluate their role in bladder and bowel dysfunction. Results from this study can help guide further research in nerve stimulation devices for bladder and bowel dysfunction in people with SCI. SPONSORSHIP: n/a.

A Flexible Implant for Multi-Day Monitoring of Colon Segment Activity.

Monitoring of colon activity is currently limited to tethered systems like anorectal manometry. These systems have significant drawbacks, but fundamentally limit the observation time of colon activity, reducing the likelihood of detecting specific clinical events. While significant technological advancement has been directed to mobile sensor capsules, this work describes the development and feasibility of a stationary sensor for describing the coordinated activity between neighboring segments of the colon. Unlike wireless capsules, this device remains in position and measures propagating pressure waves and impedances between colon segments to describe activity and motility. This low-power, flexible, wireless sensor-the colon monitor to capture activity (ColoMOCA) was validated in situ and in vivo over seven days of implantation. The ColoMOCA diameter was similar to common endoscopes to allow for minimally invasive diagnostic placement. The ColoMOCA included two pressure sensors, and three impedance-sensing electrodes arranged to describe the differential pressures and motility between adjacent colon segments. To prevent damage after placement in the colon, the ColoMOCA was fabricated with a flexible polyimide circuit board and a silicone rubber housing. The resulting device was highly flexible and suitable for surgical attachment to the colon wall. In vivo testing performed in eleven animals demonstrated suitability of both short term (less than 3 hours) and 7-day implantations. Data collected wirelessly from animal experiments demonstrated the ColoMOCA described colon activity similarly to wired catheters and allowed untethered, conscious monitoring of organ behavior.

Minimally invasive electrical rectal stimulation promotes bowel emptying in an individual with spinal cord injury.

CONTEXT: Individuals with SCI typically live with neurogenic bowel dysfunction and impaired colonic motility that may significantly impact health and quality of life. Bowel management often includes digital rectal stimulation (DRS) to modulate the recto-colic reflex to promote bowel emptying. This procedure can be time-consuming, caregiver-intensive, and lead to rectal trauma. This study presents a description of using electrical rectal stimulation as an alternative to DRS to help manage bowel emptying in a person with SCI. METHODS: We conducted an exploratory case study with a 65-year-old male with a T4 AIS B SCI who normally relies on DRS as the main component of his regular bowel management strategy. In randomly selected bowel emptying sessions during a 6-week period, the participant received burst-pattern electrical rectal stimulation (ERS) (50 mA, 20 pulses/s at 100 Hz), via a rectal probe electrode until bowel emptying was achieved. The primary outcome measure was number of cycles of stimulation required to complete the bowel routine. RESULTS: 17 sessions were performed using ERS. In 16 sessions, a bowel movement was produced after only 1 cycle of ERS. In 13 sessions, complete bowel emptying was achieved with 2 cycles of ERS. CONCLUSIONS: ERS was associated with effective bowel emptying. This work represents the first time ERS has been used to affect bowel emptying in someone with SCI. This approach could be investigated as a tool to evaluate bowel dysfunction, and it could be further refined as a tool for improving bowel emptying.

Automated closed-loop stimulation to inhibit neurogenic bladder overactivity.

Individuals with spinal cord injury (SCI) usually develop neurogenic detrusor overactivity (NDO), resulting in bladder urgency and incontinence, and reduced quality of life. Electrical stimulation of the genital nerves (GNS) can inhibit uncontrolled bladder contractions in individuals with SCI. An automated closed-loop bladder neuromodulation system currently does not exist but could improve this approach. We have developed a custom algorithm to identify bladder contractions and trigger stimulation from bladder pressure data without need for abdominal pressure measurement. The goal of this pilot study was to test the feasibility of automated closed-loop GNS using our custom algorithm to identify and inhibit reflex bladder contractions in real time. Experiments were conducted in a single session in a urodynamics laboratory in four individuals with SCI and NDO. Each participant completed standard cystometrograms without and with GNS. Our custom algorithm monitored bladder vesical pressure and controlled when GNS was turned on and off. The custom algorithm detected bladder contractions in real time, successfully inhibiting a total of 56 contractions across all four subjects. There were eight false positives, six of those occurring in one subject. It took approximately 4.0 ± 2.6 s for the algorithm to detect the onset of a bladder contraction and trigger stimulation. The algorithm maintained stimulation for approximately 3.5 ± 1.7 s, which was enough to inhibit activity and relieve feelings of urgency. Automated closed-loop stimulation was well-tolerated and subjects reported that algorithm decisions generally matched with their perceptions of bladder activity. The custom algorithm automatically, successfully identified bladder contractions to trigger stimulation to inhibit bladder contractions acutely. Closed-loop neuromodulation using our custom algorithm is feasible, but further testing is needed refine this approach for use in a home environment.

Needs, priorities, and attitudes of individuals with spinal cord injury toward nerve stimulation devices for bladder and bowel function: a survey.

STUDY DESIGN: Survey. OBJECTIVES: To investigate the needs and priorities of people with spinal cord injury for managing neurogenic bladder and bowel function and to determine their willingness to adopt neuromodulation interventions for these functions. METHODS: Anonymous online survey. It was advertised by word-of-mouth by community influencers and social media, and by advertisement in newsletters of advocacy groups. RESULTS: Responses from 370 individuals (27% female, 73% male) were included. Bladder emptying without catheters was the top priority for restoring bladder function, and maintaining fecal continence was the top priority for restoring bowel function. The biggest concerns regarding external stimulation systems were wearing a device with wires connecting to electrodes on the skin and having to don and doff the system daily as needed. The biggest concerns for implanted systems were the chances of experiencing problems with the implant that required a revision surgery or surgical removal of the whole system. Respondents were willing to accept an external (61%) or implanted (41%) device to achieve improved bladder or bowel function. CONCLUSIONS: Bladder and bowel dysfunction remain important unmet challenges for individuals living with SCI who answered our survey. These individuals are willing to accept some potential risks of nerve stimulation approaches given potential benefits. Additional consumer input is critical for guiding both research and translation to clinical use and personalized medicine.

Electrical Colon Stimulation Reflexively Increases Colonic Activity.

OBJECTIVES: Most individuals with spinal cord injury have neurogenic bowel dysfunction, which includes slowed colonic motility and has a significant impact on their health and quality of life. Bowel management typically includes mechanical rectal distension to evoke a recto-colic reflex and promote bowel emptying. Electrical stimulation could replace this mechanical distension. The purpose of this study was to determine the feasibility of evoking colonic activity using electrical stimulation. MATERIALS AND METHODS: Acute experiments were conducted in eight neural-intact cats under chloralose anesthesia. Patterned electrical stimulation was administered via electrodes placed on the surface of the distal colon or proximal colon. Distal and proximal colon pressures were measured using saline-filled balloon catheters. Outcome measures included peak colonic pressure; time to onset of response; and time to peak pressure compared to baseline without stimulation. RESULTS: Stimulation elicited colonic activity in all animals. Peak colon pressures were 15 ± 28 cmH2 O and were proportional to stimulation amplitudes. Time to onset and time to peak pressure were 13 ± 19 s and 37 ± 49 s, respectively, and were not significantly affected by stimulus parameters. Proximal colon stimulation only resulted in pressure responses from the proximal colon, but distal colon stimulation resulted in both proximal and distal responses in 40% of trials. Adding isoflurane anesthesia removed this proximal response to distal stimulation. CONCLUSIONS: Distal colon stimulation evoked colonic activity. The dependence of this response on stimulation location and anesthesia suggests that responses were reflex mediated. Colonic stimulation may have the potential to improve colonic motility for individuals with neurogenic bowel dysfunction.

Interdisciplinary bodyweight management program for persons with SCI.

Objective: Persons with spinal cord injury (SCI) have a higher prevalence of being overweight than the general population, which is thought to be due to a variety of metabolic, physiologic and psychological changes. The quality improvement project described in this work was designed to help overweight persons with SCI lose bodyweight through nutrition, exercise, and behavioral management strategies.Methods: Eighteen persons with SCI who were overweight were enrolled in a 12-week interdisciplinary weight management program. Participants were limited to persons at least one-year post-acute SCI with an established overweight status. Measurements, including a person's weight, body mass index, and waist circumference (WaC), were taken at the program's start, at its end, and six months post program.Results: Seventeen out of 18 participants experienced weight loss, (WaC) decreased (P < 0.001), and the program was effective at reducing weight (P < 0.001). Six months following participation in the program participants did experience a significant change in weight or waist size six months post program, thus indicating that subjects did not regain weight after completion of the program.Conclusion: This quality improvement project provided indications of the benefits of an SCI-specific interdisciplinary weight management program. Clinical research evaluating methods for helping persons with SCI achieve a healthy bodyweight is indicated.

Neural engineering: the process, applications, and its role in the future of medicine.

OBJECTIVE: Recent advances in neural engineering have restored mobility to people with paralysis, relieved symptoms of movement disorders, reduced chronic pain, restored the sense of hearing, and provided sensory perception to individuals with sensory deficits. APPROACH: This progress was enabled by the team-based, interdisciplinary approaches used by neural engineers. Neural engineers have advanced clinical frontiers by leveraging tools and discoveries in quantitative and biological sciences and through collaborations between engineering, science, and medicine. The movement toward bioelectronic medicines, where neuromodulation aims to supplement or replace pharmaceuticals to treat chronic medical conditions such as high blood pressure, diabetes and psychiatric disorders is a prime example of a new frontier made possible by neural engineering. Although one of the major goals in neural engineering is to develop technology for clinical applications, this technology may also offer unique opportunities to gain insight into how biological systems operate. MAIN RESULTS: Despite significant technological progress, a number of ethical and strategic questions remain unexplored. Addressing these questions will accelerate technology development to address unmet needs. The future of these devices extends far beyond treatment of neurological impairments, including potential human augmentation applications. Our task, as neural engineers, is to push technology forward at the intersection of disciplines, while responsibly considering the readiness to transition this technology outside of the laboratory to consumer products. SIGNIFICANCE: This article aims to highlight the current state of the neural engineering field, its links with other engineering and science disciplines, and the challenges and opportunities ahead. The goal of this article is to foster new ideas for innovative applications in neurotechnology.

Effects of Genital Nerve Stimulation Amplitude on Bladder Capacity in Spinal Cord Injured Subjects.

BACKGROUND/PURPOSE: Few studies have investigated the effects of changing the amplitude of dorsal genital nerve stimulation (GNS) on the inhibition of neurogenic detrusor overactivity in individuals with spinal cord injury (SCI). The present study determined the acute effects of changes in GNS amplitude on bladder capacity gain in individuals with SCI and neurogenic detrusor overactivity. METHODS: Cystometry was used to assess the effects of continuous GNS on bladder capacity during bladder filling. The cystometric trials were conducted in a randomized sequence of cystometric fills with continuous GNS at stimulation amplitudes ranging from 1 to 4 times of threshold (T) required to elicit the genitoanal reflex. RESULTS: The bladder capacity increased minimally and maximally by approximately 34% and 77%, respectively, of the baseline bladder capacity at 1.5 T and 3.2 T, respectively. Stimulation amplitude and bladder capacity were significantly correlated (R = 0.55, P = 0.01). CONCLUSION: This study demonstrates a linear correlation between the stimulation amplitude ranging from 1 to 4T and bladder capacity gain in individuals with SCI in acute GNS experiments. However, GNS amplitude out of the range of 1-4T might not be exactly a linear relationship due to subthreshold or saturation factors. Thus, further research is needed to examine this issue. Nevertheless, these results may be critical in laying the groundwork for understanding the effectiveness of acute GNS in the treatment of neurogenic detrusor overactivity.

Neuromodulation for Functional Electrical Stimulation.

This article describes the application of neuromodulation in different ways to motor recovery, to replace lost function, or to improve function of organ systems for those who have experienced spinal cord injury or stroke. Multiple devices have been developed and are currently available for use whereas others are still in the experimental stage. Multiple uses of neuromodulation are described.

At-home genital nerve stimulation for individuals with SCI and neurogenic detrusor overactivity: A pilot feasibility study.

OBJECTIVE: Neurogenic bladder dysfunction, including neurogenic detrusor overactivity (NDO) is one of the most clinically significant problems for persons with spinal cord injury (SCI), affecting health and quality of life. Genital nerve stimulation (GNS) can acutely inhibit NDO-related reflex bladder contractions and increase bladder capacity. However, it is unknown if GNS can improve urinary continence or help meet individuals' bladder management goals during sustained use, which is required for GNS to be clinically effective. DESIGN: Subjects maintained voiding diaries during a one-month control period without stimulation, one month with at-home GNS, and one month after GNS. Urodynamics and quality of life assessments were conducted after each treatment period, and a satisfaction survey was taken at study completion. SETTING: Subject screening and clinical procedures were conducted at the Louis Stokes Cleveland VA Medical Center. Stimulation use and voiding diary entries were conducted in subjects' homes. PARTICIPANTS: Subjects included five men with SCI and NDO. INTERVENTIONS: This study tested one month of at-home portable non-invasive GNS. OUTCOME MEASURES: The primary outcome measure was leakage events per day. Secondary outcome measures included self-reported subject satisfaction, bladder capacity, and stimulator use frequency. RESULTS: GNS reduced the number of leakage events from 1.0 ± 0.5 to 0.1 ± 0.4 leaks per day in the four subjects who reported incontinence data. All study participants were satisfied that GNS met their bladder goals; wanted to continue using GNS; and would recommend it to others. CONCLUSIONS: Short term at-home GNS reduced urinary incontinence and helped subjects meet their bladder management goals. These data inform the design of a long-term clinical trial testing of GNS as an approach to reduce NDO.

An Interdisciplinary Approach to Reducing Opioid Prescriptions to Patients with Chronic Pain in a Spinal Cord Injury Center.

BACKGROUND: The increasing use of prescription opioids has contributed to the epidemic of opioid abuse in the United States. Efforts to reduce opioid prescriptions and offer alternatives for pain management are needed. OBJECTIVE: To determine the success of a multidisciplinary project to manage chronic pain while reducing reliance on opioids in a population of patients with spinal cord injury (SCI). DESIGN: Retrospective analysis. SETTING: This study was conducted in an SCI system of care in northeast Ohio. PARTICIPANTS: Individuals with SCI receiving outpatient care were included. INTERVENTIONS: Clinicians in SCI and pain management specialties developed a plan to manage individuals with SCI, particularly for individuals using opioids, including physical, occupational, recreational, and vocational therapy. These services worked closely with the SCI physicians when chronic pain was identified to help better medically manage their pathology and support efforts to decrease opioid use in a multipronged approach. MAIN OUTCOMES: The primary outcome measures from opioid prescription data from 2008 to 2016 were the percent of outpatients receiving opioids, opioid prescription rates, and opioid prescription doses over time. RESULTS: The percentage of outpatients receiving opioids and the number of opioid prescriptions through the outpatient service significantly decreased, from 39% to 16% and from 2.5 to 1.5 prescriptions per patient per quarter, respectively, correlating with the introduction of the multidisciplinary interventions. The total morphine equivalent quantities of prescription medications, particularly nonmethadone opioids, also decreased significantly. CONCLUSIONS: The multidisciplinary interventional approach was associated with marked decreases in the percentage of patients receiving opioids and the amounts of opioids being prescribed. This reduction could have a significant impact on the opioid crisis. LEVEL OF EVIDENCE: IV.

Sensors Selection for Continuous Monitoring of Bowel State and Activity.

New research and diagnosis tools are needed to continuously measure bowel state and activity. We investigated functionality of several sensors in vivo and in vitro. Five sensor types, including pressure, infrared, color, conductivity and capacitance, were tested to validate functionality inside the colon. Initial wired prototypes were tested and calibrated in benchtop testing and then inserted intraluminally into pig colon and rectum in three acute surgical procedures. The results from both benchtop and in-vivo testing correlate and indicate that pressure, conductivity, and capacitance measurements could provide information on the state of the bowel and its activity.

A Conductance-Based Sensor to Estimate Bladder Volume in Felines.

New research tools are essential to help understand the neural control of the lower urinary tract (LUT). A more nuanced understanding of the neuroanatomy of bladder function could enable new treatment options or neuroprosthesis to eliminate incontinence. Here we describe the design, prototyping and validation of a sensing mechanism for a catheter-free fluid volume estimating system for chronic neurophysiological studies of the lower urinary tract and ambulatory urodynamics. The system consists of two stimulation electrodes, one sensing anode, and a microcontroller for control and recording. The packaged device is small enough to be surgically implanted within the bladder lumen, where it does not inhibit bladder function nor inflict trauma. Benchtop evaluation of the conductance-sensing system in simulated bladder-like conditions has demonstrated that the system can predict intra-vesical fluid volume with $< 5$ mL mean error below 40mL and worst-case mean error of 13mL near full-scale volume. These results indicate that conductance-based volume sensing of the urinary bladder is a feasible method for real-time measurement.

Genital nerve stimulation is tolerable and effective for bladder inhibition in sensate individuals with incomplete SCI.

BACKGROUND: Neurogenic detrusor overactivity after spinal cord injury (SCI) causes urinary incontinence and reduces bladder capacity. Surface electrical genital nerve stimulation (GNS) acutely inhibits reflex bladder contractions. The stimulation amplitude selected for GNS is typically twice the amplitude that is required to evoke the pudendal-anal reflex. There is concern about the ability of persons with sensation to comfortably tolerate effective levels of GNS. The objective of this work is to determine if persons with incomplete SCI are able to tolerate acute GNS for bladder inhibition. METHODS: Twenty-four subjects with neurogenic detrusor overactivity, SCI, and pelvic sensation were enrolled in this case series. The setting was the Spinal Cord Injury Service of a Veterans Affairs Medical Center. Primary outcome measures were sensation threshold and tolerable stimulation amplitude; secondary outcome measures were bladder capacity and bladder contraction inhibition. RESULTS: GNS was tolerable up to 30±16 mA (range 8 mA to ≥60 mA) at amplitudes greater than twice the pudendal-anal (PA) reflex threshold, which was 8±5 mA (range 4 mA to 20 mA). Twelve subjects tolerated GNS at greater than twice the PA, six tolerated 1-1.5 times the PA, and five had no identifiable PA. GNS at tolerable amplitudes inhibited reflexive bladder contractions or increased bladder capacity 135±109 mL (n=23). GNS did not cause autonomic dysreflexia or intolerable spasticity. CONCLUSIONS: GNS is tolerable at amplitudes that effectively inhibit neurogenic detrusor overactivity in individuals with pelvic sensation. GNS therefore is a tool with potential clinical applications for persons with preserved sensation.

Low-cost, Implantable Wireless Sensor Platform for Neuromodulation Research.

The role of peripheral nerves in regulating major organ function in health and disease is not well understood. Elucidating the relationships between biomarkers and neural activity during conditions free form anesthesia is essential to advancing future investigations of autonomic organ control and improving precision for neuromodulation treatment approaches. Here we present a simple, customizable, off-the-shelf component sensor platform to meet research needs for studying different organs under conscious, free movement. The platform consists of a small, rechargeable coin-cell battery, an energy-harvesting IC, a low-power microcontroller, a low-power pressure transducer, customizable number of electrodes with a common anode, inductive recharge input, and OOK inductive transmission. A case study demonstrating a bladder implant for long-term monitoring is presented, utilizing a novel, non-hermetic encapsulation approach. The customized platform uses two sleep modes to minimize battery loading, exhibiting a maximum time-averaged current draw of 125 micro-amps during sensing and transmission, with a quiescent current draw of 95 nano-amps into the microcontroller.

Genital nerve stimulation increases bladder capacity after SCI: A meta-analysis.

BACKGROUND: Neurogenic detrusor overactivity (NDO) often results in decreased bladder capacity, urinary incontinence, and vesico-ureteral reflux. NDO can trigger autonomic dysreflexia and can impair quality of life. Electrical stimulation of the genital nerves (GNS) acutely inhibits reflex bladder contractions and can increase bladder capacity. Quantifying the effect of GNS on bladder capacity and determining what study factors and subject factors influence bladder capacity improvements will inform the design of clinical GNS interventions. METHODS: We measured bladder capacity in 33 individuals with NDO, with and without GNS. These data were combined with data from seven previous GNS studies (n=64 subjects). A meta-analysis of the increase in bladder capacity and potential experimental factors was conducted (n=97 subjects total). RESULTS: Bladder capacity increased 131±101 ml with GNS across subjects in all studies. The number of individuals whose bladder capacity was greater than 300 ml increased from 24% to 62% with GNS. Stimulus amplitude was a significant factor predicting bladder capacity gain. The variance of the bladder capacity gain significantly increased with increasing infusion rate. Other factors did not contribute to bladder capacity gain. CONCLUSION: GNS acutely increases bladder capacity in individuals with NDO. The consistent increase in magnitude of bladder capacities across the eight studies, and the lack of dependence on individual-specific factors, provide confidence that GNS could be an effective tool for many individuals with NDO. Studies of the chronic effect of GNS on bladder control, with clinical measures such as urinary continence, are needed.

The neural response properties and cortical organization of a rapidly adapting muscle sensory group response that overlaps with the frequencies that elicit the kinesthetic illusion.

Kinesthesia is the sense of limb movement. It is fundamental to efficient motor control, yet its neurophysiological components remain poorly understood. The contributions of primary muscle spindles and cutaneous afferents to the kinesthetic sense have been well studied; however, potential contributions from muscle sensory group responses that are different than the muscle spindles have not been ruled out. Electrophysiological recordings in peripheral nerves and brains of male Sprague Dawley rats with a degloved forelimb preparation provide evidence of a rapidly adapting muscle sensory group response that overlaps with vibratory inputs known to generate illusionary perceptions of limb movement in humans (kinesthetic illusion). This group was characteristically distinct from type Ia muscle spindle fibers, the receptor historically attributed to limb movement sensation, suggesting that type Ia muscle spindle fibers may not be the sole carrier of kinesthetic information. The sensory-neural structure of muscles is complex and there are a number of possible sources for this response group; with Golgi tendon organs being the most likely candidate. The rapidly adapting muscle sensory group response projected to proprioceptive brain regions, the rodent homolog of cortical area 3a and the second somatosensory area (S2), with similar adaption and frequency response profiles between the brain and peripheral nerves. Their representational organization was muscle-specific (myocentric) and magnified for proximal and multi-articulate limb joints. Projection to proprioceptive brain areas, myocentric representational magnification of muscles prone to movement error, overlap with illusionary vibrational input, and resonant frequencies of volitional motor unit contraction suggest that this group response may be involved with limb movement processing.