Beneficial carry-over effects of chronic at-home genital nerve stimulation on incontinence in individuals with spinal cord injury: A pragmatic trial.

BACKGROUND: Genital nerve stimulation (GNS) is a promising, but under-researched, alternative treatment for neurogenic detrusor overactivity (NDO) in those with spinal cord injury (SCI). OBJECTIVES: To investigate the urodynamic, quality-of-life (QOL) and carry-over effects of GNS when applied at home for 2 weeks by participants with incomplete SCI and NDO during activities of daily living. METHODS: Seven men and 1 woman participated in this 1-month protocol study. Urodynamic and QOL data were gathered during week 1 (baseline measurements), followed by 2 weeks of daily GNS at home using a portable device. GNS was applied either on-demand or thrice daily, depending on the individual's sensation. At week 4, post-stimulation tests were repeated to record any carry-over effect from the GNS. Participants maintained voiding diaries throughout the study. Assessments were carried out at the end of each protocol period in a randomized order. Clinical procedures were conducted at Taipei Medical University Hospital (Taipei, Taiwan). RESULTS: Everyone completed the study but only 7 of the 8 participants completed their voiding diary. Two weeks after GNS, average cystometric bladder capacity was increased by 30 % compared to baseline (P< 0.05). A 1-week carry-over effect was demonstrated as this capacity remained, on average, 35 % greater than baseline in week 4 after GNS was stopped (P< 0.05). Incontinence frequency significantly decreased by the end of week 3 (P< 0.05) but no significant improvements were recorded for either detrusor pressure or bladder compliance. CONCLUSIONS: Chronic at-home GNS improved cystometric bladder capacity and reduced urinary incontinence for individuals with incomplete SCI and NDO. A carry-over effect of 1 week was observed following GNS treatment. The use of portable GNS treatment that can be applied by the individual at home merits further investigation as alternative treatment for NDO in those with SCI.

Deep-learning segmentation of fascicles from microCT of the human vagus nerve.

Introduction: MicroCT of the three-dimensional fascicular organization of the human vagus nerve provides essential data to inform basic anatomy as well as the development and optimization of neuromodulation therapies. To process the images into usable formats for subsequent analysis and computational modeling, the fascicles must be segmented. Prior segmentations were completed manually due to the complex nature of the images, including variable contrast between tissue types and staining artifacts. Methods: Here, we developed a U-Net convolutional neural network (CNN) to automate segmentation of fascicles in microCT of human vagus nerve. Results: The U-Net segmentation of ~500 images spanning one cervical vagus nerve was completed in 24 s, versus ~40 h for manual segmentation, i.e., nearly four orders of magnitude faster. The automated segmentations had a Dice coefficient of 0.87, a measure of pixel-wise accuracy, thus suggesting a rapid and accurate segmentation. While Dice coefficients are a commonly used metric to assess segmentation performance, we also adapted a metric to assess fascicle-wise detection accuracy, which showed that our network accurately detects the majority of fascicles, but may under-detect smaller fascicles. Discussion: This network and the associated performance metrics set a benchmark, using a standard U-Net CNN, for the application of deep-learning algorithms to segment fascicles from microCT images. The process may be further optimized by refining tissue staining methods, modifying network architecture, and expanding the ground-truth training data. The resulting three-dimensional segmentations of the human vagus nerve will provide unprecedented accuracy to define nerve morphology in computational models for the analysis and design of neuromodulation therapies.

Fascicles split or merge every ∼560 microns within the human cervical vagus nerve.

Objective.Vagus nerve stimulation (VNS) is Food and Drug Administration-approved for epilepsy, depression, and obesity, and stroke rehabilitation; however, the morphological anatomy of the vagus nerve targeted by stimulatation is poorly understood. Here, we used microCT to quantify the fascicular structure and neuroanatomy of human cervical vagus nerves (cVNs).Approach.We collected eight mid-cVN specimens from five fixed cadavers (three left nerves, five right nerves). Analysis focused on the 'surgical window': 5 cm of length, centered around the VNS implant location. Tissue was stained with osmium tetroxide, embedded in paraffin, and imaged on a microCT scanner. We visualized and quantified the merging and splitting of fascicles, and report a morphometric analysis of fascicles: count, diameter, and area.Main results.In our sample of human cVNs, a fascicle split or merge event was observed every ∼560µm (17.8 ± 6.1 events cm-1). Mean morphological outcomes included: fascicle count (6.6 ± 2.8 fascicles; range 1-15), fascicle diameter (514 ± 142µm; range 147-1360µm), and total cross-sectional fascicular area (1.32 ± 0.41 mm2; range 0.58-2.27 mm).Significance.The high degree of fascicular splitting and merging, along with wide range in key fascicular morphological parameters across humans may help to explain the clinical heterogeneity in patient responses to VNS. These data will enable modeling and experimental efforts to determine the clinical effect size of such variation. These data will also enable efforts to design improved VNS electrodes.

Both high fat and high carbohydrate diets impair vagus nerve signaling of satiety.

Obesity remains prevalent in the US. One potential treatment is vagus nerve stimulation (VNS), which activates the sensory afferents innervating the stomach that convey stomach volume and establish satiety. However, current VNS approaches and stimulus optimization could benefit from additional understanding of the underlying neural response to stomach distension. In this study, obesity-prone Sprague Dawley rats consumed a standard, high-carbohydrate, or high-fat diet for several months, leading to diet-induced obesity in the latter two groups. Under anesthesia, the neural activity in the vagus nerve was recorded with a penetrating microelectrode array while the stomach was distended with an implanted balloon. Vagal tone during distension was compared to baseline tone prior to distension. Responses were strongly correlated with stomach distension, but the sensitivity to distension was significantly lower in animals that had been fed the nonstandard diets. The results indicate that both high fat and high carbohydrate diets impair vagus activity.

Sources of off-target effects of vagus nerve stimulation using the helical clinical lead in domestic pigs.

Objective: Clinical data suggest that efficacious vagus nerve stimulation (VNS) is limited by side effects such as cough and dyspnea that have stimulation thresholds lower than those for therapeutic outcomes. VNS side effects are putatively caused by activation of nearby muscles within the neck, via direct muscle activation or activation of nerve fibers innervating those muscles. Our goal was to determine the thresholds at which various VNS-evoked effects occur in the domestic pig­an animal model with vagus anatomy similar to human­using the bipolar helical lead deployed clinically. Approach: Intrafascicular electrodes were placed within the vagus nerve to record electroneurographic (ENG) responses, and needle electrodes were placed in the vagal-innervated neck muscles to record electromyographic (EMG) responses. Main results: Contraction of the cricoarytenoid muscle occurred at low amplitudes (~0.3 mA) and resulted from activation of motor nerve fibers in the cervical vagus trunk within the electrode cuff which bifurcate into the recurrent laryngeal branch of the vagus. At higher amplitudes (~1.4 mA), contraction of the cricoarytenoid and cricothyroid muscles was generated by current leakage outside the cuff to activate motor nerve fibers running within the nearby superior laryngeal branch of the vagus. Activation of these muscles generated artifacts in the ENG recordings that may be mistaken for compound action potentials representing slowly conducting Aδ-, B-, and C-fibers. Significance: Our data resolve conflicting reports of the stimulation amplitudes required for C-fiber activation in large animal studies (>10 mA) and human studies (<250 µA). After removing muscle-generated artifacts, ENG signals with post-stimulus latencies consistent with Aδ- and B-fibers occurred in only a small subset of animals, and these signals had similar thresholds to those that caused bradycardia. By identifying specific neuroanatomical pathways that cause off-target effects and characterizing the stimulation dose-response curves for on- and off-target effects, we hope to guide interpretation and optimization of clinical VNS.

Functional vagotopy in the cervical vagus nerve of the domestic pig: implications for the study of vagus nerve stimulation.

OBJECTIVE: Given current clinical interest in vagus nerve stimulation (VNS), there are surprisingly few studies characterizing the anatomy of the vagus nerve in large animal models as it pertains to on-and off-target engagement of local fibers. We sought to address this gap by evaluating vagal anatomy in the pig, whose vagus nerve organization and size approximates the human vagus nerve. APPROACH: Here we combined microdissection, histology, and immunohistochemistry to provide data on key features across the cervical vagus nerve in a swine model, and compare our results to other animal models (mouse, rat, dog, non-human primate) and humans. MAIN RESULTS: In a swine model we quantified the nerve diameter, number and diameter of fascicles, and distance of fascicles from the epineural surface where stimulating electrodes are placed. We also characterized the relative locations of the superior and recurrent laryngeal branches of the vagus nerve that have been implicated in therapy limiting side effects with common electrode placement. We identified key variants across the cohort that may be important for VNS with respect to changing sympathetic/parasympathetic tone, such as cross-connections to the sympathetic trunk. We discovered that cell bodies of pseudo-unipolar cells aggregate together to form a very distinct grouping within the nodose ganglion. This distinct grouping gives rise to a larger number of smaller fascicles as one moves caudally down the vagus nerve. This often leads to a distinct bimodal organization, or 'vagotopy'. This vagotopy was supported by immunohistochemistry where approximately half of the fascicles were immunoreactive for choline acetyltransferase, and reactive fascicles were generally grouped in one half of the nerve. SIGNIFICANCE: The vagotopy observed via histology may be advantageous to exploit in design of electrodes/stimulation paradigms. We also placed our data in context of historic and recent histology spanning multiple models, thus providing a comprehensive resource to understand similarities and differences across species.

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.

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.

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.

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.

Ultrasound-Guided Steroid Injection of the Pisotriquetral Joint: A Multidisciplinary Effort.

From the perspective of a multidisciplinary team, the authors describe the first reported use of ultrasound guidance for steroid injection into the pisotriquetral joint to relieve wrist pain of a person with spinal cord injury undergoing acute inpatient rehabilitation. Musculoskeletal ultrasound guidance was used to improve the accuracy of a corticosteroid injection of the pisotriquetral joint and the basal thumb in a 70-year-old man with paraplegia experiencing multifocal degenerative wrist pain. There was no bleeding or bruising after the injections, and the patient reported complete pain resolution 1 wk after the injections, which continued for over 1 yr. A multidisciplinary team was key in diagnosis, selection of treatment, and evaluation of treatment effect. Corticosteroid injection of the pisotriquetral joint under ultrasound guidance can be used as a treatment modality for managing wrist pain stemming from that joint. Further investigation and studies evaluating the use of ultrasound versus other imaging modalities for injection of the wrist are indicated.

Suburothelial Bladder Contraction Detection with Implanted Pressure Sensor.

AIMS: Managing bladder pressure in patients with neurogenic bladders is needed to improve rehabilitation options, avoid upper tract damage, incontinence, and their associated co-morbidities and mortality. Current methods of determining bladder contractions are not amenable to chronic or ambulatory settings. In this study we evaluated detection of bladder contractions using a novel piezoelectric catheter-free pressure sensor placed in a suburothelial bladder location in animals. METHODS: Wired prototypes of the pressure monitor were implanted into 2 nonsurvival (feline and canine) and one 13-day survival (canine) animal. Vesical pressures were obtained from the device in both suburothelial and intraluminal locations and simultaneously from a pressure sensing catheter in the bladder. Intravesical pressure was monitored in the survival animal over 10 days from the suburothelial location and necropsy was performed to assess migration and erosion. RESULTS: In the nonsurvival animals, the average correlation between device and reference catheter data was high during both electrically stimulated bladder contractions and manual compressions (r = 0.93±0.03, r = 0.89±0.03). Measured pressures correlated strongly (r = 0.98±0.02) when the device was placed in the bladder lumen. The survival animal initially recorded physiologic data, but later this deteriorated. However, endstage intraluminal device recordings correlated (r = 0.85±0.13) with the pressure catheter. Significant erosion of the implant through the detrusor was found. CONCLUSIONS: This study confirms correlation between suburothelial pressure readings and intravesical bladder pressures. Due to device erosion during ambulatory studies, a wireless implant is recommended for clinical rehabilitation applications.

Restoration from acute urinary dysfunction using Utah electrode arrays implanted into the feline pudendal nerve.

OBJECTIVES: To investigate intrafascicular pudendal nerve stimulation in felines as a means to restore urinary function in acute models of urinary incontinence, overactive bladder, and underactive bladder. MATERIALS AND METHODS: Felines were anesthetized, and high-electrode-count (48 electrodes; 25 electrodes/mm(2) ) electrode arrays were implanted intrafascicularly into the pudendal nerve trunk. Electrodes were mapped for their ability to selectively or nonselectively excite the external anal sphincter, external urethral sphincter, and the detrusor bladder muscle. Statistical analysis was carried out to quantify reflexive voiding efficiencies, mean impedances of the microelectrodes used in this study, and to determine what differences, if any, in bladder contraction amplitudes were evoked by different electrode configurations. RESULTS: Multielectrode arrays implanted into the pudendal nerve trunk were able to selectively and nonselectively excite genitourinary muscles. After inducing urinary incontinence with bilateral pudendal nerve transections (proximal to the implants), electrical stimulation delivered through certain microelectrodes was able to significantly reduce leaking (p = 0.008). Electrical stimulation delivered through detrusor selective electrodes was able to inhibit reflexive bladder contractions and excite bladder contractions, depending on the stimulation frequency. Specific electrode configurations were able to drive significantly (p < 0.001) larger bladder contractions than other electrode configurations, depending on the preparation. Successful reflexively or electrically driven bladder contractions were achieved in 46% and 38% of the preparations, respectively, an observation that has not been noted in previously published feline pudendal stimulation studies. CONCLUSIONS: Multielectrode arrays implanted intrafascicularly into the pudendal nerve trunk may provide a promising new clinical neuromodulation therapy for the restoration of urinary function.

Does patterned afferent stimulation of sacral dermatomes suppress urethral sphincter reflexes in individuals with spinal cord injury?

AIMS: Dyssynergic contractions of the external urethral sphincter prevent efficient bladder voiding and lead to numerous health concerns. Patterned electrical stimulation of the sacral dermatomes reduces urethral sphincter spasms and allows functional bladder emptying in cats after chronic SCI. Reflex suppression in animals is strongly dependent on stimulus location and pattern. The purpose of this study was to determine whether the stimulation patterns and locations effective in animals suppress urethral sphincter spasms in humans with SCI. METHODS: Ten subjects with chronic SCI underwent bladder filling to elicit distention-evoked contractions. During reflex contractions patterned electrical stimulation was applied to the S2 or S3 dermatome in random 25-sec intervals. Bladder and sphincter pressures were simultaneously recorded and compared between control and afferent stimulation periods. RESULTS: Six of the 10 subjects demonstrated both reflex bladder and sphincter contractions with bladder filling. No significant reduction in urethral pressure was observed during stimulation for any stimulus locations and patterns tested. CONCLUSIONS: Stimulation parameters and locations effective in SCI animals did not suppress reflex sphincter activity in these human subjects. It is likely that a broader set of stimulus patterns and dermatome locations will need to be tested to find the effective combination in humans.

Functional electrical stimulation and spinal cord injury.

Spinal cord injuries (SCI) can disrupt communications between the brain and the body, resulting in loss of control over otherwise intact neuromuscular systems. Functional electrical stimulation (FES) of the central and peripheral nervous system can use these intact neuromuscular systems to provide therapeutic exercise options to allow functional restoration and to manage medical complications following SCI. The use of FES for the restoration of muscular and organ functions may significantly decrease the morbidity and mortality following SCI. Many FES devices are commercially available and should be considered as part of the lifelong rehabilitation care plan for all eligible persons with SCI.

Different clinical electrodes achieve similar electrical nerve conduction block.

OBJECTIVE: We aim to evaluate the suitability of four electrodes previously used in clinical experiments for peripheral nerve electrical block applications. APPROACH: We evaluated peripheral nerve electrical block using three such clinical nerve cuff electrodes (the Huntington helix, the Case self-sizing Spiral and the flat interface nerve electrode) and one clinical intramuscular electrode (the Memberg electrode) in five cats. Amplitude thresholds for the block using 12 or 25 kHz voltage-controlled stimulation, onset response, and stimulation thresholds before and after block testing were determined. MAIN RESULTS: Complete nerve block was achieved reliably and the onset response to blocking stimulation was similar for all electrodes. Amplitude thresholds for the block were lowest for the Case Spiral electrode (4 ± 1 Vpp) and lower for the nerve cuff electrodes (7 ± 3 Vpp) than for the intramuscular electrode (26 ± 10 Vpp). A minor elevation in stimulation threshold and reduction in stimulus-evoked urethral pressure was observed during testing, but the effect was temporary and did not vary between electrodes. SIGNIFICANCE: Multiple clinical electrodes appear suitable for neuroprostheses using peripheral nerve electrical block. The freedom to choose electrodes based on secondary criteria such as ease of implantation or cost should ease translation of electrical nerve block to clinical practice.

Electrical stimulation of sacral dermatomes can suppress aberrant urethral reflexes in felines with chronic spinal cord injury.

AIMS: Uncoordinated reflex contractions of the external urethral sphincter (EUS) are a major component of voiding dysfunction after neurologic injury. Patterned stimulation of sacral afferent pathways can reduce abnormal EUS reflexes after acute spinal cord injury (SCI); however, effectiveness following chronic SCI is unknown. METHODS: Four adult male cats were implanted with bilateral extradural sacral root electrodes to allow bladder activation and underwent subsequent spinal transection (T10-12). Nine weeks after SCI urethral and bladder pressures were recorded with and without sacral afferent stimulation. Surface electrodes were applied to sacral and lumbar dermatomes and stimulus amplitude set below the muscle fasciculation threshold. The stimulation pattern was varied by on/off times of fixed frequency at each location. RESULTS: Reflexive EUS contractions were observed in all animals after chronic SCI. Patterned sacral dermatome stimulation reduced EUS reflex rate and amplitude in two of four cats. Suppression was dependent on both the stimulus location and pattern. Sacral locations and a stimulation pattern of (0.75 sec on, 0.25 sec off, 20 Hz) were effective in both responder animals. CONCLUSIONS: Patterned sacral dermatome stimulation can reduce abnormal urethral reflexes following chronic SCI. Reflex suppression is dependent on both the stimulation location and stimulus pattern. Reduction of reflexive EUS activity after chronic SCI with this non-destructive and non-invasive approach may provide an advance for the treatment of detrusor-sphincter-dyssynergia.

Human distal sciatic nerve fascicular anatomy: implications for ankle control using nerve-cuff electrodes.

The design of neural prostheses to restore standing balance, prevent foot drop, or provide active propulsion during ambulation requires detailed knowledge of the distal sciatic nerve anatomy. Three complete sciatic nerves and branches were dissected from the piriformis to each muscle entry point to characterize the branching patterns and diameters. Fascicle maps were created from serial sections of each distal terminus below the knee through the anastomosis of the tibial and common fibular nerves above the knee. Similar branching patterns and fascicle maps were observed across specimens. Fascicles innervating primary plantar flexors, dorsiflexors, invertors, and evertors were distinctly separate and functionally organized in the proximal tibial, common fibular, and distal sciatic nerves; however, fascicles from individual muscles were not apparent at these levels. The fascicular organization is conducive to selective stimulation for isolated and/or balanced dorsiflexion, plantar flexion, eversion, and inversion through a single multicontact nerve-cuff electrode. These neuroanatomical data are being used to design nerve-cuff electrodes for selective control of ankle movement and improve current lower-limb neural prostheses.

High frequency sacral root nerve block allows bladder voiding.

AIMS: Dyssynergic reflexive external urethral sphincter (EUS) activity following spinal cord injury can prevent bladder voiding, resulting in significant medical complications. Irreversible sphincterotomies or neurotomies can prevent EUS activation and allow bladder voiding, but may cause incontinence or loss of sacral reflexes. We investigated whether kilohertz frequency (KF) electrical conduction block of the sacral roots could prevent EUS activation and allow bladder voiding. METHODS: The S2 sacral nerve roots were stimulated bilaterally to generate bladder pressure in six cats. One S1 nerve root was stimulated proximally (20 Hz biphasic pulse trains) to evoke EUS pressure, simulating worst-case dyssynergic EUS reflexes. KF waveforms (12.5 kHz biphasic square wave) applied to an electrode implanted distally on the S1 nerve root blocked nerve conduction, preventing the increase in EUS pressure and allowing voiding. RESULTS: Applying KF waveforms increased bladder voiding in single, limited-duration trials from 3 ± 6% to 59 ± 12%. Voiding could be increased to 82 ± 9% of the initial bladder volume by repeating or increasing the duration of the trials. CONCLUSIONS: Sacral nerve block can prevent EUS activation and allow complete bladder voiding, potentially eliminating the need for a neurotomy. Eliminating neurotomy requirements could increase patient acceptance of bladder voiding neuroprostheses, increasing patient quality of life and reducing the cost of patient care.