Sensing in Sacral Neuromodulation: A Feasibility Study in Subjects With Urinary Incontinence and Retention.

OBJECTIVES: Sacral neuromodulation (SNM) therapy standard of care relies on visual-motor responses and patient-reported sensory responses in deciding optimized lead placement and programming. Automatic detection of stimulation responses could offer a simple, consistent indicator for optimizing SNM. The purpose of this study was to measure and characterize sacral evoked responses (SERs) resulting from sacral nerve stimulation using a commercial, tined SNM lead. MATERIALS AND METHODS: A custom external research system with stimulation and sensing hardware was connected to the percutaneous extension of an implanted lead during a staged (tined lead) evaluation for SNM. The system collected SER recordings across a range of prespecified stimulation settings (electrode configuration combinations for bipolar stimulation and bipolar sensing) during intraoperative and postoperative sessions in 21 subjects with overactive bladder (OAB) and nonobstructive urinary retention (NOUR). Motor and sensory thresholds were collected during the same sessions. RESULTS: SERs were detected in all 21 subjects. SER morphology (number of peaks, magnitude, and timing) varied across electrode configurations within and across subjects. Among subjects and electrode configurations tested, recordings contained SERs at motor threshold and/or sensory threshold in 75% to 80% of subjects. CONCLUSIONS: This study confirmed that implanted SNM leads can be used to directly record SERs elicited by stimulation in subjects with OAB and NOUR. SERs were readily detectable at typical SNM stimulation settings and procedural time points. Using these SERs as possible objective measures of SNM response has the capability to automate patient-specific SNM therapy, potentially providing consistent lead placement, programming, and/or closed-loop therapy.

[Sacral Neuromodulation for Fecal Incontinence and Constipation: Evidence, Programming and Long-term Management]. / Sakralnervmodulation in der Therapie der Stuhlinkontinenz und Obstipation: Evidenz, Programmierung und Langzeitmanagement.

BACKGROUND: Over the last two decades, sacral neuromodulation (SNM) has established its role in the treatment of functional pelvic organ-/pelvic floor disorders. Even though the mode of action is not fully understood, SNM has become the preferred surgical treatment of fecal incontinence. METHODS AND RESULTS: A literature search was carried out on programming sacral neuromodulation and long-term outcomes in treating fecal incontinence and constipation.Sacral neuromodulation was found to be successful in the long term. Over the years, the spectrum of indications has expanded, and now includes patients presenting with anal sphincter lesions. The use of SNM for low anterior resection syndrome (LARS) is currently under clinical investigation. Findings of SNM for constipation are less convincing. In several randomised crossover studies, no success was demonstrated, even though it is possible that subgroups may benefit from the treatment. Currently the application cannot be recommended in general.The pulse generator programming sets the electrode configuration, amplitude, pulse frequency and pulse width. Usually pulse frequency and pulse width follow a default setting (14 Hz, 210 s), while electrode configuration and stimulation amplitude are adjusted individually to the patient need and perception of stimulation.Despite low infection rates and few electrode-/pulse generator dysfunctions, up to 65% of patients require surgical reintervention during long term follow-up - in 50% of cases because of battery depletion, which is an expected event. At least one reprogramming is necessary in about 75% of the patients during the course of the treatment, mostly because of changes in effectiveness, but rarely because of pain. Regular follow-up visits appear to be advisable. CONCLUSION: Sacral neuromodulation can be considered to be a safe and effective long-term therapy of fecal incontinence. To optimise the therapeutic effect, a structured follow-up regime is advisable.

Activation of MrgprA3 and MrgprC11 on Bladder-Innervating Afferents Induces Peripheral and Central Hypersensitivity to Bladder Distension.

Understanding the sensory mechanisms innervating the bladder is paramount to developing efficacious treatments for chronic bladder hypersensitivity conditions. The contribution of Mas-gene-related G protein-coupled receptors (Mrgpr) to bladder signaling is currently unknown. Using male and female mice, we show with single-cell RT-PCR that subpopulations of DRG neurons innervating the mouse bladder express MrgprA3 (14%) and MrgprC11 (38%), either individually or in combination, with high levels of coexpression with Trpv1 (81%-89%). Calcium imaging studies demonstrated MrgprA3 and MrgprC11 agonists (chloroquine, BAM8-22, and neuropeptide FF) activated subpopulations of bladder-innervating DRG neurons, showing functional evidence of coexpression between MrgprA3, MrgprC11, and TRPV1. In ex vivo bladder-nerve preparations, chloroquine, BAM8-22, and neuropeptide FF all evoked mechanical hypersensitivity in subpopulations (20%-41%) of bladder afferents. These effects were absent in recordings from Mrgpr-clusterΔ-/- mice. In vitro whole-cell patch-clamp recordings showed that application of an MrgprA3/C11 agonist mixture induced neuronal hyperexcitability in 44% of bladder-innervating DRG neurons. Finally, in vivo instillation of an MrgprA3/C11 agonist mixture into the bladder of WT mice induced a significant activation of dorsal horn neurons within the lumbosacral spinal cord, as quantified by pERK immunoreactivity. This MrgprA3/C11 agonist-induced activation was particularly apparent within the superficial dorsal horn and the sacral parasympathetic nuclei of WT, but not Mrgpr-clusterΔ-/- mice. This study demonstrates, for the first time, functional expression of MrgprA3 and MrgprC11 in bladder afferents. Activation of these receptors triggers hypersensitivity to distension, a critically valuable factor for therapeutic target development.SIGNIFICANCE STATEMENT Determining how bladder afferents become sensitized is the first step in finding effective treatments for common urological disorders such as overactive bladder and interstitial cystitis/bladder pain syndrome. Here we show that two of the key receptors, MrgprA3 and MrgprC11, that mediate itch from the skin are also expressed on afferents innervating the bladder. Activation of these receptors results in sensitization of bladder afferents, resulting in sensory signals being sent into the spinal cord that prematurely indicate bladder fullness. Targeting bladder afferents expressing MrgprA3 or MrgprC11 and preventing their sensitization may provide a novel approach for treating overactive bladder and interstitial cystitis/bladder pain syndrome.

Sacral neuromodulation for the prevention of a permanent stoma in patients with severe defecation disorder following intersphincteric resection.

PURPOSE: Severe defecation disorder occurs frequently in coloanal anastomosis for low rectal cancer, and may affect quality of life. Sacral neuromodulation (SNM) has been reported to be successful after rectal resection, but there are no results for patients treated with intersphincteric resection (ISR). METHODS: A retrospective single-center study of SNM was performed for patient with defecation disorder following ISR. Pre- and post-treatment bowel frequencies, fecal incontinence episodes, and Wexner, LARS and FIQL scores were assessed to evaluate the efficacy. A good response was defined as ≥ 50% reduction of bowel frequency per day or fecal incontinence episodes per week. RESULTS: 10 patients (7 males, mean age 67.5 years) underwent SNM. All patients had severe fecal incontinence with a median Wexner score of 15 (13-20) and a median LARS score of 41 (36-41). The Wexner score improved after SNM, but not significantly (p = 0.06). LARS and FIQL scores significantly improved after SNM (p = 0.02, p = 0.01). At the end of follow-up, the good response rate was 40%. Three cases without a good response required creation of a permanent stoma. CONCLUSION: Seven out of 10 patients did not require a permanent colostomy after SNM. SNM should be considered before performing a permanent colostomy.

Sacral Neuromodulation: Determining Predictors of Success.

OBJECTIVE: To determine predictors of success for sacral neuromodulation in women with overactive bladder, urinary retention, and fecal incontinence. METHODS: A retrospective chart review was performed on women who underwent a staged sacral neuromodulation implantation between 2007 and 2018. Clinical and procedural characteristics were recorded. Presence of intraoperative motor responses in either all 4 or <4 electrodes were used to group women. Endpoints included completion of stage II implant, tined lead revision, and patient-reported success. RESULTS: In 198 women with a mean age of 62.9 years (SD+/- 14.7), completion of stage II implant occurred in 92.4% of women, and 83.3% of these women reported success at the first postoperative visit. Continued success at 6 months was reported in 70.3%. Lead revision was noted in 23.0%. Age >65 years (odds ratio [OR] = 0.2, 95% confidence interval [CI] = 0.06-0.8) and prior onabotulinumtoxinA (onaBoNT-A) (OR = 0.2, 95% CI = 0.06-0.9) were negative predictors for completion of stage II implant on multivariable analysis. Also, prior pelvic floor physical therapy was a significant negative predictor of postoperative patient-reported success on multivariable analysis (OR = 0.25, 95% CI = 0.1-0.6). There were no differences seen in women who had motor responses with either all 4 electrodes or <4 electrodes in any endpoint (P > .05). CONCLUSION: Patient age >65 and history of prior onaBoNT-A were associated with failure to complete stage II implant. Women with prior pelvic floor physical therapy were less likely to report success after sacral neuromodulation. Motor responses in <4 electrodes during lead testing did not impact patient-reported success.

Fecal Incontinence in the Elderly.

Fecal incontinence can be a challenging and stigmatizing disease with a high prevalence in the elderly population. Despite effective treatment options, most patients do not receive care. Clues in the history and physical examination can assist the provider in establishing the diagnosis. Direct inquiry about the presence of incontinence is key. Bowel disturbances are common triggers for symptoms and represent some of the easiest treatment targets. We review the epidemiology and impact of the disease, delineate a diagnostic and treatment approach for primary care physicians to identify patients with suspected fecal incontinence and describe appropriate treatment options.

Sacral Nerve Stimulation in Parkinson's Disease Patients With Overactive Bladder Symptoms.

OBJECTIVE: To assess the efficacy, safety, and outcomes of sacral nerve stimulation (SNS) for Parkinson's disease (PD) patients with overactive bladder symptoms. METHODS: We retrospectively reviewed PD patients who underwent Stage I SNS. Demographics, urodynamic data, and baseline voiding function were analyzed. Efficacy and safety of treatment were determined by rate of progression to Stage II, explantation, and surgical revision. Long-term outcomes were assessed using voiding diaries and/or clinic notes. RESULTS: Sixty percent (9/15) experienced ≥50% improvement in urinary parameters and proceeded to Stage II. There was no significant difference in age, body mass index, comorbidities, PD disease duration, or levodopa equivalent daily dose between successful and nonsuccessful Stage I patients. However, 100% of female patients experienced Stage I success compared to 44% of male PD patients (P = .04). Individuals with >12-month follow-up experienced an average reduction of 6 voids/day. No patients required revision or explantation of their device at latest clinic follow-up (22.2 ± 7.8 months). Higher maximal urethral closure pressures, detrusor pressure at maximum flow rate (PdetQmax), post-void residual volume, and mean bladder outlet obstruction index were observed in the Stage I trial failures. CONCLUSION: At our institution, PD patients have a similar rate of progression to Stage II compared to the general population. SNS is an effective therapy that should be considered among the treatment options for PD patients with overactive bladder symptoms. Urodynamic parameters associated with obstruction may be predictive of SNS failure in PD patients and may help guide patient selection, however further studies are needed.

Pelvic floor activation upon stimulation of the sacral spinal nerves in sacral neuromodulation patients.

PURPOSE: To assess the activation of the different parts of the pelvic floor muscles (PFM) upon electrical stimulation of the sacral spinal nerves while comparing the different lead electrode configurations. MATERIAL AND METHODS: PFM electromyography (EMG) was recorded using an intravaginal multiple array probe with 12 electrodes pairs, which allows to make a distinction between the different sides and depths of the pelvic floor. In addition concentric needle EMG of the external anal sphincter was performed to exclude far-field recording. A medtronic InterStim tined lead (model 3889) was used as stimulation source. Standard SNM parameters (monophasic pulsed square wave, 210 microseconds, 14 Hz) were used to stimulate five different bipolar electrode configurations (3+0-/3+2-/3+1-/0+3-/1+3-) up to and around the sensory threshold. Of each EMG signal the stimulation intensity needed to evoke the EMG signals as well as its amplitude and latency were determined. Linear mixed models was used to analyse the data. RESULTS: Twenty female patients and 100 lead electrode configurations were stimulated around the sensory response threshold resulting in 722 stimulations and 12 times as many (8664) EMG recordings. A significant increase in EMG amplitude was seen upon increasing stimulation intensity (P < .0001). Large differences were noted between the EMG amplitude recorded at the different sides (ipsilateral>posterior>anterior>contralateral) and depths (deep>center>superficial) of the pelvic floor. These differences were noted for all lead electrodes configurations stimulated (P < .0001). Larger EMG amplitudes were measured when the active electrode was located near the entry point of the sacral spinal nerves through the sacral foramen (electrode #3). No differences in EMG latency could be withheld, most likely due to the sacral neuroanatomy (P > .05). CONCLUSIONS: A distinct activation pattern of the PFM could be identified for all stimulated lead electrode configurations. Electrical stimulation with the most proximal electrode (electrode #3) as the active one elicited the largest PFM contractions.

Sacral nerve stimulation ameliorates colonic barrier functions in a rodent model of colitis.

BACKGROUND: The mucosal barrier damage is recognized as one of the key factors in the pathogenesis of colitis. While sacral nerve stimulation (SNS) was reported to have therapeutic potential for colitis, its mechanisms of actions on colonic permeability remained largely unknown. METHODS: In this study, colitis was induced by intrarectal administration of TNBS in rats. Five days later, they were treated with SNS or sham-SNS for 10 days. The effects of SNS on colonic permeability were assessed by measuring the expression of tight-junction proteins involved in regulating permeability and the FITC-dextran test. The mechanism of actions of SNS was investigated by studying the function of the enteric nervous system (ENS) cells and analyzing the autonomic nervous system. KEY RESULTS: SNS decreased the disease activity index, microscopic and macroscopic scores, myeloperoxidase activity, and pro-inflammatory cytokines (TNF-α, IL-6). SNS increased the expression of Zonula Occludens-1, Occludin, Claudin-1, and Junctional adhesion molecule-A in the colon tissue. The FITC-dextran test showed that the colonic permeability was lower with SCS than sham-SNS. SNS increased ChAT, pancreatic polypeptide, and GDNF and reduced norepinephrine NGF, sub-P, and mast cell overactivation in the colon tissue. Concurrently, SNS increased acetylcholine in colon tissues and elevated vagal efferent activity. CONCLUSIONS & INFERENCES: SNS ameliorates colonic inflammation and enhances colonic barrier function with the proposed mechanisms involving the increase in parasympathetic activity and modulation of the activity of the ENS and immune system, including mast cells.

A novel method of sacral nerve stimulation for colonic inflammation.

BACKGROUND: Vagal nerve stimulation has been reported to treat inflammation with promising results. The aims of our study were to optimize sacral nerve stimulation (SNS) methodologies for colonic inflammation in a rodent model of colitis and to investigate autonomic and cytokine mechanisms. METHODS: Three major efforts were made in optimizing SNS: (a) to determine the best stimulation duration: SNS-0.5h daily, SNS-1h daily, and SNS-3h daily with the parameters set at 5 Hz, 10 seconds on, 90 seconds off; (b) to determine the best stimulation position: bilateral, bipolar, and unipolar stimulation; (c) to determine the best stimulation parameters: our 5 Hz intermittent stimulation vs 14 Hz-210 µs continuous stimulation. Inflammatory responses were assessed by the disease activity index (DAI), histological analyses, and the myeloperoxidase (MPO) activity. Levels of inflammatory cytokines, norepinephrine (NE), and pancreatic polypeptide (PP) in both plasma and colon tissues were assessed. KEY RESULTS: Both SNS-1h and SNS-3h significantly ameliorated intestinal inflammation; SNS-1h was superior to SNS-3h. Bipolar but not bilateral or unipolar stimulation improved the inflammation in colitis. SNS with 5 Hz intermittent stimulation but not the 14 Hz continuous SNS was better for treating colitis in rats. SNS with the optimized stimulation parameters increased vagal activity and decreased sympathetic activity. CONCLUSION & INFERENCES: Bipolar stimulation for 1 hour daily using intermittent 5 Hz parameters is most effective in improving colonic inflammation in TNBS-treated rats by inhibiting pro-inflammatory cytokines and increasing anti-inflammatory cytokines via the modulation of the autonomic function.

Ameliorating effects of sacral neuromodulation on gastric and small intestinal dysmotility mediated via a sacral afferent-vagal efferent pathway.

BACKGROUND/AIMS: In a recent study of sacral nerve stimulation (SNS) for colonic inflammation, a possible spinal-vagal pathway was implicated. The aim of this study was to provide evidence for such a pathway by investigating the effects of SNS on dysmotility of the stomach and duodenum that are not directly innervated by the sacral efferents. METHODS: Twenty-seven rats were chronically implanted with wire electrodes for SNS and gastrointestinal slow waves. SNS was performed in several acute sessions to investigate its effects on gastric/duodenal slow waves and emptying/transit impaired by glucagon and rectal distention (RD). RESULTS: (a) SNS increased the percentage of normal gastric slow waves impaired by glucagon (from 53.9% to 77.0%, P < .0001) and RD (from 64% to 78%, P = .037). This improvement was abolished by atropine. (b) Similar effects were observed with SNS on duodenal slow waves, which was also blocked by atropine. (c) SNS normalized delayed gastric emptying induced by glucagon (control: 61.3%, glucagon: 44.3%, glucagon + SNS: 65.8%) and RD (control: 61.3%, RD: 46.7%, RD + SNS: 64.3%). It also normalized small intestinal transit delayed by RD (P = .001, RD + SNS vs RD; P = .9, RD + SNS vs control). (4) Both glucagon and RD induced an increase in the sympathovagal ratio (P = .007, glucagon vs baseline; P < .001, RD vs baseline) and SNS decreased the ratio (P = .006, glucagon + SNS vs glucagon; P = .04, RD + SNS vs RD). CONCLUSIONS: Neuromodulation of the sacral nerve improves gastric and small intestinal pacemaking activity and transit impaired by glucagon and RD by normalizing the sympathovagal balance via a retrograde neural pathway from the sacral nerve to vagal efferents.

Sacral nerve stimulation increases gastric accommodation in rats: a spinal afferent and vagal efferent pathway.

Impaired gastric accommodation (GA) has been frequently reported in various gastrointestinal diseases. No standard treatment strategy is available for treating impaired GA. We explored the possible effect of sacral nerve stimulation (SNS) on GA and discovered a spinal afferent and vagal efferent mechanism in rats. Sprague-Dawley rats (450-500 g) with a chronically implanted gastric cannula and ECG electrodes were studied in a series of sessions to study: 1) the effects of SNS with different parameters on gastric tone, compliance, and accommodation using a barostat device; two sets of parameters were tested as follows: parameter 1) 5 Hz, 500 µs, 10 s on 90 s off; 90% motor threshold and parameter 2) same as parameter 1 but 25 Hz; 2) the involvement of spinal afferent pathway via detecting c-fos immunoreactive (IR) cells in the nucleus of the solitary tract (NTS) of the brain; 3) the involvement of vagal efferent activity via the spectral analysis of heart rate variability derived from the ECG; and 4) the nitrergic mechanism, Nω-nitro-l-arginine methyl ester (l-NAME), a nitric oxide synthase (NOS) inhibitor, was given before SNS at 5 Hz. Compared with sham-SNS: 1) SNS at 5 Hz inhibited gastric tone and increased gastric compliance and GA. No difference was noted between the stimulation frequencies of 5 and 25 Hz. 2) SNS increased the expression of c-fos in the NTS. 3) SNS increased cardiac vagal efferent activity and decreased the sympathovagal ratio. 4) l-NAME blocked the relaxation effect of SNS. In conclusion, SNS with certain parameters relaxes gastric fundus and improves gastric accommodation mediated via a spinal afferent and vagal efferent pathway.NEW & NOTEWORTHY Currently, there is no adequate medical therapy for impaired gastric accommodation, since medications that relax the fundus often impair antral peristalsis and thus further delay gastric emptying that is commonly seen in patients with functional dyspepsia or gastroparesis. The advantage of the potential sacral nerve stimulation therapy is that it improves gastric accommodation by enhancing vagal activity, and the enhanced vagal activity would lead to enhanced antral peristalsis rather than inhibiting it.

Sacral nerve stimulation with appropriate parameters improves constipation in rats by enhancing colon motility mediated via the autonomic-cholinergic mechanisms.

Although sacral nerve stimulation (SNS) has been applied for treating constipation, its parameters were adopted from SNS for fecal incontinence, its effects are limited, and mechanisms are largely unknown. We investigated the effects and mechanism of SNS with appropriate parameters on constipation in rats treated with loperamide. First, using rectal compliance as an outcome measure, an experiment was performed to derive effective SNS parameters. Then, a 7-day SNS was performed in rats with constipation induced by loperamide. Autonomic functions were assessed by spectral analysis of heart rate variability (HRV) derived from an electrocardiogram. Serum levels of pancreatic polypeptide (PP), norepinephrine (NE), and acetylcholine (ACh) in colon were assessed. 1) Acute SNS at 5 Hz, 100 µs was found effective in enhancing rectal compliance and accelerating distal colon transit (P < 0.05 vs. sham SNS). 2) The 7-day SNS normalized loperamide-induced constipation, assessed by the number, weight, and water content of fecal pellets, and accelerated the distal colon transit (29.4 ± 3.7 min with sham SNS vs. 16.4 ± 5.3 min with SNS but not gastric emptying or intestinal transit. 3) SNS significantly increased vagal activity (P = 0.035) and decreased sympathetic activity (P = 0.012), assessed by spectral analysis of HRV as well as by the serum PP. 4) SNS increased ACh in the colon tissue; atropine blocked the accelerative effect of SNS on distal colon transit. We concluded that SNS with appropriate parameters improves constipation induced by loperamide by accelerating distal colon motility, mediated via the autonomic-cholinergic function.NEW & NOTEWORTHY Although sacral nerve stimulation (SNS) has been applied for treating constipation, its parameters were adopted from SNS for fecal incontinence, effects are limited, and mechanisms are largely unknown. This paper shows that SNS with appropriate parameters improves constipation induced by loperamide by accelerating distal colon motility mediated via the autonomic-cholinergic function.

Spinal Manipulation Therapy Improves Tactile Allodynia and Peripheral Nerve Functionality and Modulates Blood Oxidative Stress Markers in Rats Exposed to Knee-Joint Immobilization.

OBJECTIVE: The purpose of our study was to evaluate the effect of manually assisted lumbar spinal manipulation therapy on tactile allodynia, peripheral nerve functional recovery, and oxidative markers in rats exposed to knee immobilization-inducing hypersensitivity. METHODS: Tactile allodynia and sciatic, tibial, and peroneal functional indices were assessed before the knee joint immobilization, 24 hours after the knee cast removal, and 24 hours after 3 weeks of lumbar therapy with the Activator Adjusting Instrument, model 4 (AAI 4). Subsequently, the blood was collected from each rat, and oxidative markers such as lipid hydroperoxide levels; nitric oxide metabolites; and superoxide dismutase, catalase, and glutathione peroxidase activities were assessed. RESULTS: The AAI 4 improved the immobilization-induced allodynia and recovered the peripheral nerve functional indices impaired after knee immobilization. Immobilized rats treated with AAI 4 therapy presented a lack of significant changes in lipid hydroperoxides and nitric oxide metabolites in the plasma contrasting with rats that were kept freely in their cages, with no therapy applied, which presented elevated lipid hydroperoxides levels. Also, the antioxidant catalase enzymatic activity decreased in the blood of rats immobilized and treated with AAI 4. CONCLUSION: These results suggest that manually assisted lumbar spinal manipulation therapy modulates systemic oxidative stress, which possibly contributes to the analgesia and recovery of peripheral nerve functionality.

Is Sacral Nerve Modulation a Good Option for Fecal Incontinence in Men?

OBJECTIVE: The objective was to assess the efficacy and the safety of sacral nerve modulation (SNM) in men with fecal incontinence (FI) compared with those of SNM in women. METHOD: Prospectively collected data from patients from seven tertiary colorectal units who underwent an implant procedure between January 2010 and December 2015 were reviewed retrospectively. Outcomes and surgical revision and definitive explantation rates were compared between men and women. RESULTS: A total of 469 patients (60 men [12.8%]; mean age = 61.4 ± 12.0 years) were included in the study, 352 (78.1%) (31 men [8.8%]) of whom received a permanent implant. The ratio of implanted/tested men was significantly lower than the ratio of implanted/tested women (p = 0.0004). After a mean follow-up of 3.4 ± 1.9 years, the cumulative successful treatment rates tended to be less favorable in men than in women (p = 0.0514): 88.6% (75.6-95.1), 75.9% (60.9-86.4), 63.9% (48.0-77.3), and 43.9% (26.7-62.7) at one, two, three, and five years, respectively, in men; 92.0% (89.1-94.2), 84.2% (80.3-87.4), 76.8% (72.3-80.7), and 63.6% (57.5-69.3) at one, two, three, and five years, respectively, in women. The revision rate for infection and the definitive explantation rate for infection were higher in men than in women (p = 0.0001 and p = 0.0024, respectively). CONCLUSION: Both short- and long-term success rates of SNM for FI were lower in men than in women. The revision and definitive explantation for long-term infection rates were significantly higher in men.

Outcomes of Sacral Nerve Stimulation for Treatment of Refractory Overactive Bladder Among Octogenarians.

OBJECTIVE: Sacral nerve stimulation (SNS) is an effective treatment for refractory overactive bladder (OAB). However, advanced age is often cited as a reason to avoid SNS in the elderly. This study evaluates the safety and efficacy of SNS for refractory OAB among our octogenarian population. METHODS: A retrospective review from a single institution was performed on all SNS lead placements from December 1998 to June 2017 for refractory OAB. Octogenarians were characterized as 80 years of age or older at the time of Stage I. Efficacy and safety were determined by the rate of progression to Stage II, subsequent need for multimodal therapy, and rate of surgical revision and explantation. All patients were followed for a minimum of 12 months. RESULTS: Of 374 patients in this study, 37 (9.9%) were octogenarians. There was no difference in gender, race, smoking history, or prior OAB treatment regimens between cohorts. The rate of progression to Stage II was 56.8% for octogenarians compared to 60.5% for nonoctogenarians (p = 0.66). The rate of surgical revision, explantation, and need for multimodal therapy did not differ between groups. Subgroup analysis of octogenarians did not reveal any significant differences between successful and nonsuccessful Stage I patients. CONCLUSIONS: The safety and efficacy of SNS was similar between cohorts. This result suggests that SNS is a safe and effective therapy that should be considered among the treatment options for refractory OAB in octogenarian patients. Further studies are needed to determine predictive factors of Stage I success in elderly patients.

Urethral regions with differential tissular composition may underlie urinary continence and voiding function in female rats.

AIMS: To analyze, in female rats, the anatomical and histological features of the urethra and its relationship with the vagina and clitoris, and its innervation. METHODS: Seventeen adult female Wistar rats were used. Gross anatomy and acetylcholinesterase (AchE) histochemistry were performed to describe the urethral features, adjacent structures, and innervation. The histomorphometric characteristics of the urethra were determined in transversal, longitudinal, or coronal sections stained with Masson's Trichrome. RESULTS: The female rat urethra is not a homogeneous tubular organ. The pre-pelvic and pelvic regions are firmly attached to the vagina with belt-like striated fibers forming a urethra-vaginal complex. The bulbar regions have curved segments and a narrow lumen. The clitoral region is characterized by a urethra-clitoral complex surrounded by a vascular plexus. The lumen area and thickness of the urethral layers significantly varied between regions (P < 0.05). Innervation of the urethra arrives from the major pelvic ganglion, the dorsal nerve of the clitoris (DNC), and the motor branch of the sacral plexus (MBSP). CONCLUSIONS: Differential tissular composition of the urethra may underlie urinary continence and voiding dysfunction through different physiological mechanisms. The urethra-vagina complex seems to be the main site controlling urinary continence through active muscular mechanisms, while the bulbar urethra provides passive mechanisms and the urethra-clitoris complex seems to be crucial for distal urethral closure by means of a periurethral vascular network.