Acute Autonomic Nervous System Response to Direct Sacral Nerve Root Stimulation in Lower Urinary Tract Dysfunction: A New Approach to Understand the Mechanism of Action of Sacral Nerve Modulation.

PURPOSE: Our goal was to assess acute autonomic nervous system (ANS) response to direct sacral nerve root (SNR) stimulation in the context of lower urinary tract dysfunction. MATERIALS AND METHODS: In this retrospective monocentric study, patients undergoing 2-stage sacral nerve modulation for overactive bladder, nonobstructive urinary retention, or chronic bladder pain syndrome between March 2022 and June 2023 were analyzed. A standardized stimulation protocol was applied during the lead implantation, each of the 4 contact points being sequentially stimulated at the amplitude required to elicit anal motor response. Stimulations were labeled as StimA, StimB, StimC, and StimD, ordered by ascending order of minimum amplitude required for anal motor response. Heart rate variability parameters were collected using PhysioDoloris Monitor, and computed through the time-domain (standard deviation of normal-to-normal intervals [SDNN], root mean square of successive differences), the frequency-domain (low frequency, high frequency) and the graphical (Analgesia Nociception Index [ANI]) methods. RESULTS: Fifty patients were analyzed, including 35 females. Twelve patients had an underlying neurological disease. Efficacy was deemed achieved in 54% of patients. SDNN variability significantly increased during StimA to StimC, while maximum SDNN significantly increased only during StimA. ANI variability significantly increased during all 4 stimulations, while maximum ANI significantly increased only during StimA. CONCLUSIONS: Direct stimulation of SNR is responsible for a significant increase in ANS and relative parasympathetic nervous system activity, with a greater effect observed when the stimulation was delivered closer to the SNR. These results shed light on potential mechanisms underlying sacral nerve modulation, particularly regarding the treatment of ANS dysregulation in lower urinary tract dysfunction.

Do patients experience decisional regret after sacral neuromodulation for refractory overactive bladder?

OBJECTIVE: Success following urological procedures is traditionally defined through objective endpoints. This approach may not capture the impact on patient satisfaction. There is a paucity of literature evaluating patient-centered metrics such as satisfaction and decisional regret in the field of urology. This study investigates long-term satisfaction and decisional regret amongst patients who underwent sacral neuromodulation (SNM) for the treatment of refractory overactive bladder (OAB). MATERIALS AND METHODS: This study retrospectively reviewed patients who underwent SNM for refractory OAB from 2015 to 2022 at a single institution serving an ethnically diverse and underrepresented community. Demographic data were collected through chart review and surveys conducted via telephone calls. Patient satisfaction and decisional regret was measured with the validated modified SDS-DRS scale (satisfaction with decision scale-decision regret scale). Descriptive statistics, Wilcoxan rank sum, and median regression analyses were performed using STATA 15.0 with p < 0.05 as significant. RESULTS: Out of 191 patients who underwent SNM, 63 were unreachable (wrong number in chart, number not in service, patient did not answer, deceased). Eighty-nine out of 128 patients reached agreed to participate (70% response rate). The mean time since surgery was 37.3 ±25.2 months. The median satisfaction with decision score was 4.0 (IQR: 3.7-4.7) with a score of 1 correlating with low satisfaction and a score of 5 correlating with high satisfaction. The median decisional regret score was 2.0 (IQR: 1.2-2.9) with a score of 1 correlating with low decisional regret and a score of 5 correlating with strong decisional regret. Ten patients reported complications after surgery, which was significantly associated with lower SDS and higher DRS scores (p < 0.01), and persisted after adjusting for age, body mass index, sex, and comorbidities (SDS ß coef: -0.84, 95% CI: -1.5 to 0.15, p = 0.02; DRS ß coef: 1.48, 95% CI: 0.55-2.41, p < 0.01). CONCLUSIONS: Patients who underwent SNM for refractory OAB overall had low regret and high satisfaction with their decision at an average 3 years of follow-up. As expected, those who developed postoperative complications had worse scores. The inclusion of patient-centric outcomes is imperative when determining the success of a surgical procedure and is useful for shared decision-making when advancing to third-line therapy for OAB. Longer-term follow-up is necessary to assess durability of high satisfaction and low regret over time.

Does choice of anesthesia during stage 1 sacral neuromodulation testing influence outcomes?

INTRODUCTION: Staged sacral neuromodulation (SNM) testing has been shown to have a high rate of progression to permanent implantation for the management of voiding dysfunction. Stage 1 lead placement (SNM-I) can be performed under monitored anesthesia care (MAC) or general anesthesia (GA). MAC allows for interpretation of sensory and motor responses to optimize lead placement while GA only permits for motor assessment. However, patient discomfort and movement can make lead placement challenging during MAC. Herein we evaluate whether the anesthesia type impacts the progression rate to permanent implantation (SNM-II). MATERIALS AND METHODS: A retrospective chart review was performed for patients who underwent SNM-I in the operating room for wet overactive bladder between 2005 and 2023. Patients were divided into two groups based on the type of anesthesia used, MAC or GA. Clinical variables and progression to SNM-II were compared between cohorts. Progression to SNM-II was based on ≥50% symptomatic improvement during a 1-2 week trial period following SNM-I. RESULTS: Of 121 patients included in the study, 95 (79%) underwent MAC and 26 (21%) GA for SNM-I. No difference in the progression rate to SNM-II was noted between groups (MAC, 68/95 patients, 72%; GA, 19/26, 73%; p = 0.39). We also found no difference when comparing the GA group to the 26 most recent MAC patients (MAC, 20/26 patients, 77%; GA, 19/26, 73%; p = 0.48). CONCLUSION: Types of anesthesia for SNM-I did not affect rate of progression to SNM-II. The result lends support to the reliance on motor responses alone for lead placement during SNM-I.

Percutaneous tibial neuromodulation initial therapy compliance and subsequent third-line treatment patterns.

PURPOSE: Percutaneous Tibial Neuromodulation (PTNM) is used to treat Overactive Bladder (OAB). This analysis summarizes patient adherence to PTNM treatment and examines trends of other third-line therapy use during and after PTNM. METHODS: Optum's deidentified Clinformatics® Data Mart Database (CDM) and CMS Research Identifiable Files were queried for adults with OAB symptoms and who underwent PTNM treatment (2019-2020). We evaluated the proportion of patients who completed 12 visits within 1 year, and defined patients as treatment compliant if 12 PTNM visits were completed within 12 weeks. We then identified the proportion of patients who used other third-line therapies after PTNM and stratified these patients based on their PTNM therapy compliance status. RESULTS: 2302 patients met selection criteria from CDM and 16,473 patients from CMS. The proportion of patients completing a full PTNM treatment course increased over time; from 16% at week 12% to 42% by week 52 (CDM) and 24% to 38% (CMS). Other third-line therapy use increased over time and was higher for PTNM noncompliant versus compliant patients at 52 weeks: onabotulinumtoxinA was 6.5% versus 5.7% for noncompliant versus compliant (CMS, p = 0.0661) and 6.4% versus 4.9% (CDM, p = 0.035), SNM trial procedure was 6.5% versus 2.5% (CDM, p = 0.002) and 4.2% versus 2.0% (CMS, p = 0.010). CONCLUSIONS: Most patients are noncompliant with recommended PTNM treatment regimen. Albeit low, third-line therapy was pursued more frequently by noncompliant patients. Given low compliance, the effectiveness of PTNM may be compromised. Alternative implantable technologies may be needed to assure effectiveness of neuromodulation.

Sacral neuromodulation device biofilm differs in the absence and presence of infection, harbors antibiotic resistance genes, and is reproducible in vitro.

INTRODUCTION/PURPOSE: Sacral neuromodulation (SNM) is effective therapy for overactive bladder refractory to oral therapies, and non-obstructive urinary retention. A subset of SNM devices is associated with infection requiring surgical removal. We sought to compare microbial compositions of explanted devices in the presence and absence of infection, by testing phase, and other clinical factors, and to investigate antibiotic resistance genes present in the biofilms. We analyzed resistance genes to antibiotics used in commercially-available anti-infective device coating/pouch formulations. We further sought to assess biofilm reconstitution by material type and microbial strain in vitro using a continuous-flow stir tank bioreactor, which mimics human tissue with an indwelling device. We hypothesized that SNM device biofilms would differ in composition by infection status, and genes encoding resistance to rifampin and minocycline would be frequently detected. MATERIALS/METHODS: Patients scheduled to undergo removal or revision of SNM devices were consented per IRB-approved protocol (IRB 20-415). Devices were swabbed intraoperatively upon exposure, with controls and precautions to reduce contamination of the surrounding field. Samples and controls were analyzed with next-generation sequencing and RT-PCR, metabolomics, and culture-based approaches. Associations between microbial diversity or microbial abundance, and clinical variables were then analyzed using t-tests and ANOVA. Reconstituted biofilm deposition in vitro using the bioreactor was compared by microbial strain and material type using plate-based assays and scanning electron microscopy. RESULTS: Thirty seven devices were analyzed, all of which harbored detectable microbiota. Proteobacteria, Firmicutes and Actinobacteriota were the most common phyla present overall. Beta-diversity differed in the presence versus absence of infection (p = 0.014). Total abundance, based on normalized microbial counts, differed by testing phase (p < 0.001), indication for placement (p = 0.02), diabetes mellitus (p < 0.001), cardiac disease (p = 0.008) and history of UTI (p = 0.008). Significant microbe-metabolite interaction networks were identified overall and in the absence of infection. 24% of biofilms harbored the tetA tetracycline/minocycline resistance gene and 53% harbored the rpoB rifampin resistance gene. Biofilm was reconstituted across tested strains and material types. Ceramic and titanium did not differ in biofilm deposition for any tested strain. CONCLUSIONS: All analyzed SNM devices harbored microbiota. Device biofilm composition differed in the presence and absence of infection and by testing phase. Antibiotic resistance genes including to rifampin and tetracycline/minocycline, which are used in commercially-available anti-infective pouches, were frequently detected. Isolated organisms from SNM devices demonstrated the ability to reconstitute biofilm formation in vitro. Biofilm deposition was similar between ceramic and titanium, materials used in commercially-available SNM device casings. The findings and techniques used in this study together provide the basis for the investigation of the next generation of device materials and coatings, which may employ novel alternatives to traditional antibiotics. Such alternatives might include bacterial competition, quorum-sensing modulation, or antiseptic application, which could reduce infection risk without significantly selecting for antibiotic resistance.

Real-world onabotulinumtoxinA treatment patterns in patients with overactive bladder.

PURPOSE: Utilization patterns of third-line onabotulinumtoxinA for overactive bladder (OAB) symptoms-including discontinuation and use of other therapeutic options during or after treatment-are not well understood. This retrospective analysis of administrative claims was designed to characterize the unmet need for OAB treatment. MATERIALS AND METHODS: A retrospective claims analysis of Optum's deidentified Clinformatics® Data Mart Database (2009-2021) was performed among patients with diagnosis of OAB newly starting onabotulinumtoxinA injection (2015-2017). Study measures were evaluated during an 18-month pretreatment baseline and over a minimum of 36 months of follow-up. These included number of injections, days between injections, other measures of onabotulinumtoxinA utilization, use of second-line pharmacologic treatments, use of device and surgical treatment options, and complications. RESULTS: Of 2505 eligible patients, 535 (21.4%; 66.8 ± 13.3 y, 87.3% females) continued onabotulinumtoxinA throughout the study. The remaining 1970 (78.6%; 71.4 ± 11.6 y, 79.1% females) were considered discontinuers. Of continuers, 57% received ≥5 treatments. Of discontinuers, 84% received ≤2 treatments. Anticholinergics and ß3-adrenoceptor agonist medication use declined in all patients from baseline to follow-up; however, the absolute reduction in the proportion with any medication fill was similar across continuers versus discontinuers (21% vs. 18%, p < 0.0001). Sacral neuromodulation was initiated by 15/535 (3%) of continuers and 137/1970 (7%) of discontinuers (p < 0.0001). No patients initiated percutaneous tibial neuromodulation. CONCLUSIONS: Early discontinuation of onabotulinumtoxinA therapy for OAB is common and most discontinuers do not receive alternative treatments. Providers have the opportunity to educate OAB patients with un- or undertreated symptoms regarding alternative options.

Risk factors for complications following sacral neuromodulation for faecal incontinence: Long-term follow-up.

AIM: Sacral neuromodulation (SNM) has become a standard surgical treatment for faecal incontinence (FI). Prior studies have reported various adverse events of SNM, including suboptimal therapeutic response, infection, pain, haematoma, and potential need for redo SNM. The aim of this study was to identify the risk factors associated with long-term complications of SNM. METHOD: This retrospective cohort reviewed patients who underwent two-stage SNM for FI at our institution between 2011-2021. Preoperative baseline characteristics and follow-up were obtained from the medical record and/or by telephone interview. Management and outcome of each postoperative event were evaluated by univariate and multivariate regression analyses. RESULTS: A total of 291 patients (85.2% female) were included in this study. Postoperative complications were recorded in 219 (75.2%) patients and 154 (52.9%) patients required surgical intervention to treat complications. The most common postoperative event was loss of efficacy (46.4%). Other common adverse events were problems at the implant site (pain, infection, etc.) in 16.5% and pain during stimulation in 11.7%. Previous vaginal delivery (OR 2.74, p = 0.003) and anal surgery (OR = 2.46, p = 0.039) were independent predictors for complications. Previous colorectal (OR = 2.04, p = 0.026) and anal (OR = 1.98, p = 0.022) surgery and history of irritable bowel syndrome (IBS) (OR = 3.49, p = 0.003) were independent predictors for loss of efficacy. CONCLUSION: Postoperative adverse events are frequently recorded after SNM. Loss of efficacy is the most common. Previous colorectal or anal surgery, vaginal delivery, and IBS are independent risk factors for complications.

One-stage implant in sacral neuromodulation for faecal incontinence - short-term outcome from a prospective study.

AIM: Sacral neuromodulation (SNM) is approved for the treatment of faecal incontinence (FI) in a two-stage technique. With standardized implantation, approximately 90% of patients undergo successful Stage I operation and proceed to a permanent implant (Stage II). The aim of this work was to explore the feasibility of SNM as a one-stage procedure and report the 24-week efficacy. METHOD: This study included patients diagnosed with idiopathic FI or FI due to an external anal sphincter defect ≤160° and one or more episodes of FI per week despite maximal conservative therapy. Patients were offered a one-stage procedure if a motor response of the external anal sphincter was achieved in three or more poles with at least one at ≤1.5 mA at lead placement. Patients were followed for 24 weeks. Their evaluation included the Wexner/St Mark's Incontinence Score, Faecal Incontinence Quality of Life score (FIQoL), a visual analogue scale (VAS) for assessing patient satisfaction and a bowel habit diary. RESULTS: Seventy-three patients with a median age of 60 years (interquartile range 50-69 years) completed this prospective study. Episodes of FI were significantly reduced at the 24-week follow-up, from 13 (8-23) at baseline to 2 (0-5) (p-value = 0002). A ≥50% reduction in the number of FI episodes was achieved in 92% of participants. The Wexner score improved significantly from 16 (14-17) at baseline to 9 (5-13) (p-value < 0.001), and the St Mark's score improved significantly from 18 (16-20) to 11 (7-16) (p-value < 0.001). All domains in the FIQoL score and VAS for patient satisfaction improved significantly following the one-stage procedure. CONCLUSION: A one-stage implantation procedure is feasible in selected patients with FI, significantly improving continence, quality of life and patient satisfaction after 24 weeks of follow-up.

Effectiveness, safety and cost-effectiveness of sacral neuromodulation for idiopathic slow-transit constipation: a systematic review.

AIM: Sacral neuromodulation (SNM) is a minimally invasive treatment option for functional constipation. Evidence regarding its effectiveness is contradictory, driven by heterogeneous study populations and designs. The aim of this study was to assess the effectiveness, safety and cost-effectiveness of SNM in children and adults with refractory idiopathic slow-transit constipation (STC). METHOD: OVID Medline, OVID Embase, Cochrane Library, the KSR Evidence Database, the NHS Economic Evaluation Database and the International HTA Database were searched up to 25 May 2023. For effectiveness outcomes, randomized controlled trials (RCTs) were selected. For safety outcomes, all study designs were selected. For cost-effectiveness outcomes, trial- and model-based economic evaluations were selected for review. Study selection, risk of bias and quality assessment, and data extraction were independently performed by two reviewers. For the intervention 'sacral neuromodulation' effectiveness outcomes included defaecation frequency and constipation severity. Safety and cost-effectiveness outcomes were, respectively, adverse events and incremental cost-effectiveness ratios. RESULTS: Of 1390 records reviewed, 67 studies were selected for full-text screening. For effectiveness, one cross-over and one parallel-group RCT was included, showing contradictory results. Eleven studies on safety were included (four RCTs, three prospective cohort studies and four retrospective cohort studies). Overall infection rates varied between 0% and 22%, whereas reoperation rates varied between 0% and 29%. One trial-based economic evaluation was included, which concluded that SNM was not cost-effective compared with personalized conservative treatment at a time horizon of 6 months. The review findings are limited by the small number of available studies and the heterogeneity in terms of study populations, definitions of refractory idiopathic STC and study designs. CONCLUSION: Evidence for the (cost-)effectiveness of SNM in children and adults with refractory idiopathic STC is inconclusive. Reoperation rates of up to 29% were reported.

Device-Related Reoperations 8 Years Following Sacral Neuromodulation Implantation in Older Women.

INTRODUCTION AND HYPOTHESIS: The objective was to describe long-term device-related reoperations at 8 years following sacral neuromodulation (SNM) in women older than 65 years for the indications of overactive bladder (OAB), fecal incontinence (FI), and/or idiopathic urinary retention (UR). METHODS: The 2010-2019 Medicare 100% Outpatient Limited Dataset was used to identify women aged 65 years and older who underwent SNM to treat OAB, FI, and/or UR. The primary study outcome was any device-related reoperation within 8 years following initial implantable pulse generator (IPG) implantation defined as: IPG revision or removal; IPG replacement; or neuro-electrode revision or removal. Kaplan-Meier survival analysis was also performed to evaluate time to adverse event. RESULTS: The cohort included 32,454 women with a mean age of 74 years. The most common indication for SNM was OAB (71%) followed by UI and FI (13%) and FI only (8%). Staged SNM procedures were performed more frequently (60%) than percutaneous nerve evaluation/full implants. The overall rate of device-related reoperations was 24% over 8 years: 12% of patients underwent removal or revision of the neuro-electrode, 11% underwent removal or revision of the IPG, and 13% underwent replacement of the IPG. The mean follow-up was 3.9 ± 2.4 years. The cumulative incidence of any device-related reoperations was 9.4% at 1 year, 20% at 3 years, and 43% at 8 years. CONCLUSIONS: In the 8 years following SNM implantation, the rate of device-related reoperation among female Medicare beneficiaries was 43%, and staged implants were associated with a 17% lower likelihood of undergoing any device-related reoperations.

Seminal papers in urology: two-year outcomes of Sacral Neuromodulation Versus OnabotulinumtoxinA for refractory urgency urinary incontinence: a Randomized Trial.

In this critical review, we explore the study design, strengths and limitations of the paper: "Two-Year Outcomes of Sacral Neuromodulation Versus OnabotulinumtoxinA for Refractory Urgency Urinary Incontinence: A Randomized Trial." The paper reports 24 month follow-up data of the landmark ROSETTA trial. This multi-centre, open-labelled parallel randomised trial allocated females 1:1 to receive Sacral Neuromodulation (SNM) or OnabotulinumtoxinA(BTX) 200 units (U). The primary outcome was change in mean daily urinary urgency incontinence episodes (UUIE) over 24 months. The study did not demonstrate a difference between treatments (-3.88 vs. -3.50 episodes per day), however women treated with BTX were more satisfied; but reported higher rates of UTI. The two treatments provide comparable third-line treatment options for patients with refractory urgency urinary incontinence.

Outcomes of sacral neuromodulation in male patients with overactive bladder, chronic pelvic pain, and fecal incontinence.

INTRODUCTION: Despite the growing body of literature on sacral neuromodulation (SNM) outcomes, research focusing on male patients remains limited and often represented by small cohorts nested within a larger study of mostly women. Herein, we evaluated the outcomes of SNM in a male-only cohort with overactive bladder (OAB), fecal incontinence (FI), chronic bladder pain, and neurogenic lower urinary tract dysfunction (NLUTD). MATERIALS AND METHODS: This retrospective cohort study included 64 male patients who underwent SNM insertion between 2013 and 2021 at a high-volume tertiary center. Indications for SNM therapy included OAB, FI, chronic pelvic pain, and NLUTD. Descriptive statistics, Fisher's and t-test were used in analysis. RESULTS: The mean age was 57.7 ± 13.4 years, and the most frequent reason for SNM insertion was idiopathic OAB (72%), FI (16%), pelvic pain (11%), and NLUTD (11%). A majority (84%) of men received treatment prior to SNM insertion. 84% reported satisfaction and 92% symptom improvement within the first year, and these improvements persisted beyond 1 year in 73% of patients. Mean follow up was 52.7 ± 21.0 months. The complication rate was 23%, and the need for adjunct treatments was significantly reduced (73% to 27%, p < 0.001). Treatment outcomes did not differ significantly between various indications for SNM therapy or the presence of benign prostatic hyperplasia (BPH). CONCLUSION: SNM is an effective and safe procedure for male patients with neurogenic and non-neurogenic OAB, pelvic pain, and FI. Over 70% of patients experienced symptomatic improvement and remained satisfied in the mid to long term follow up. BPH does not seem to hinder treatment outcomes.

Outcomes of sequential third-line therapies in patients with refractory overactive bladder.

INTRODUCTION: Sacral neuromodulation (SNM) and onabotulinumtoxinA (BoNTA) injection are third-line therapies for overactive bladder (OAB). Although the efficacy of each third-line treatment has been well established in clinical trials, there is far less information about performing one third-line therapy after the other. Our aim is thus to investigate the outcomes of post-SNM BoNTA and post-BoNTA SNM as "second" third-line treatments. METHODS: We retrospectively reviewed all OAB patients who had both SNM and BoNTA between 2013 and 2022. The primary endpoint was the response rates (>50% improvements) of the second third-line treatments. Secondary endpoints were the proportion of the patients who achieved total dry, the duration of treatments of patients who had significant responses, and risk factors that are associated with treatment response or duration of treatments. RESULTS: A total of 172 patients had two third-line therapies. There were 104 patients who had post-SNM BoNTA and 68 patients who had post-BoNTA SNM. In the post-SNM BoNTA group, 62.5% (65/104) had significant responses after BoNTA treatment. In the post-BoNTA SNM group, 61.8% (44/68) had significant responses after SNM treatment. The proportions of patients who became dry were 21.2% and 23.5%, respectively. In the post-SNM BoNTA group, spinal pathology is associated with a lower probability of a significant response (48.9% vs. 73.7%, p-value = 0.0105). CONCLUSIONS: BoNTA or SNM remains a viable option for refractory OAB after patients fail from one another. Spinal pathology is associated with a poorer response of post-SNM BoNTA.

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.

Early Sacral Neuromodulation Prevented Detrusor Overactivity in Rats With Spinal Cord Injury.

OBJECTIVES: Sacral neuromodulation (SNM) has been shown to alleviate bladder dysfunction in patients with overactive bladder and nonobstructive urinary retention. However, the therapeutic effect and mechanism of SNM in neurogenic bladder dysfunction are still not fully understood. Using a rat model of spinal cord injury (SCI), this study aims to investigate the therapeutic effect of early SNM in the bladder-areflexia phase on neurogenic bladder dysfunction and evaluate its possible mechanism. MATERIALS AND METHODS: Basic physiological parameters such as body/bladder weight, blood pressure, and electrocardiogram results were measured to evaluate the safety of SNM. Enzyme-linked immunosorbent assays and quantitative real-time polymerase chain reaction were used to examine the expression of proinflammatory factors. Hematoxylin and eosin and Masson's trichrome staining were used to observe morphological changes, and cystometry was used to evaluate urodynamic changes after SNM treatment. Western blotting and immunofluorescence staining were used to measure the levels of transient receptor potential vanilloid 1 (TRPV1) and calcitonin gene-related peptide (CGRP) in the L6-S1 dorsal root ganglia (DRGs) and bladder. Capsaicin desensitization was used to investigate whether inhibiting TRPV1 could prevent detrusor overactivity in SCI rats. RESULTS: Early SNM did not affect the body/bladder weight, heart rate, blood pressure, or the expression of proinflammatory cytokines (PGE2, IL-1, IL-2, IL-6, TGF-ß, or TNF-α) in the bladders of SCI rats. Morphologically, early SNM prevented urothelial edema (p = 0.0248) but did not influence collagen/smooth muscle in the bladder. Compared with untreated rats with SCI, the rats treated with SNM exhibited increased bladder capacity (p = 0.0132) and voiding efficiency (p = 0.0179), and decreased nonvoiding contraction (NVC) frequency (p = 0.0240). The maximum pressure, basal pressure, postvoid residual, and NVC amplitude did not change significantly. After the SNM treatment, the expression of TRPV1 in the bladder and CGRP in L6-S1 DRGs weredecreased (L6, p = 0.0160; S1, p = 0.0024) in SCI rats. In capsaicin-desensitized SCI rats, urodynamic results showed an increase in bladder capacity (p = 0.0116) and voiding efficiency (p = 0.0048), and diminished NVC frequency (p = 0.0116), while other parameters did not change significantly. CONCLUSIONS: Early SNM prevented urothelial edema morphologically and detrusor overactivity in SCI rats. Inhibition of TRPV1 in the bladder and DRGs may be one of the potential mechanisms for preventing detrusor overactivity by SNM.

Symptom Assessment of Candidates for Sacral Neuromodulation Therapy With Urologic and Colorectal Conditions: Time for a Holistic Approach? Results and Findings From a Prospective Single-Center Study.

OBJECTIVES: Sacral neuromodulation (SNM) has evolved as a therapeutic intervention for various pelvic floor dysfunctions. However, the traditional approach primarily assesses discipline-specific symptoms, potentially overlooking holistic symptom improvement. We aimed to investigate whether a more comprehensive evaluation of pelvic floor symptoms enhances the assessment of SNM's test phase. MATERIAL AND METHODS: A prospective single-center trial (Optimization of Lower Urinary Tract Symptoms study) assessed SNM efficacy from March 2018 to December 2021 in patients from the urology department (UD) and colorectal surgery department (CRD) with a follow-up of 12 months. Objective and subjective outcomes were examined using diaries and patient-reported outcome measures. Statistical analyses were conducted to determine predictive factors for treatment success, expressed by the patient global impression of change. SPSS 29.0 was used. RESULTS: A total of 85 participants were included, displaying concomitant pelvic floor symptoms. After the first phase, significant improvements on all pelvic floor domains questionnaires were seen for both patients from UD and those from CRD. Although improvements were observed in bladder and bowel diaries, the traditional criteria for success (≥50% improvement in diary variables) did not consistently correlate with the patients' global impression of change. The absolute reductions in bother sum scores from multiple domains were significant predictors for the patients' global impression of change, outperforming discipline-specific assessments. Patients from UD benefit from both a urologic and pelvic pain symptom evaluation, and those from CRD, from both a urologic and bowel symptom evaluation. CONCLUSIONS: SNM shows positive effects across various pelvic floor domains, even beyond the primary intended indication of implantation. The rather rigid approach of patient selection of discipline-specific symptoms alone can be questioned. A more comprehensive evaluation encompassing various pelvic floor symptoms with the emphasis on subjective outcome measures could enhance SNM's efficacy assessment during the test phase. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT05313984.

Sacral Neuromodulation: Device Improvement and Current Applications in Urology.

Sacral neuromodulation (SNM) offers a therapeutic approach to urological patients suffering from idiopathic overactive bladder (OAB) syndrome, with or without incontinence and non-obstructive urinary retention (NOR), who are not responding to or are not compliant with conservative or medical therapies. The exact mechanism of action of SNM is not fully understood but modulation of the spinal cord reflexes and brain networks by peripheral afferents is regarded as the main pathway. Over the years, surgical techniques improved, leading to the development of the modern two-stage implantation technique. The quadripolar lead is positioned percutaneously under fluoroscopy guidance through the third sacral foramen following the trajectory of S3. The procedure can be performed under local or general anesthesia with the patient in prone position. Current applications of sacral neuromodulation in urology are increasing thanks to the recent improvements of the devices that make this a valuable option not only in conditions such as overactive bladder and non-obstructing urinary retention but also neurogenic lower urinary tract dysfunction.

[Prolonged spinal and sacral neurostimulation in children with pelvic organ dysfunction: preliminary analysis]. / Dlitel'naya spinal'naya i sakral'naya neirostimulyatsiya u detei pri narusheniyakh funktsii tazovykh organov: predvaritel'nyi analiz.

OBJECTIVE: To evaluate the clinical efficacy of long-term spinal and sacral programmable neurostimulation for pelvic organ dysfunction in patients with myelodysplasia and chronic dysfunction of the bladder and rectum. MATERIAL AND METHODS: A retrospective study included 32 children aged 1-17 years (mean 10.7) with myelodysplasia, pelvic organ dysfunction and ineffective therapy including botulinum therapy and exclusion of tethered spinal cord syndrome. All children underwent comprehensive urodynamic examination with analysis of bladder and residual urine volume, mean flow rate, intravesical pressure and total urine volume, as well as electromyographic examination. Examination was carried out before surgery, after 6, 12 and 36 months. We applied urinary diary, NBSS questionnaire and urodynamic examination data. All patients underwent neurological examinations (neurological status, magnetic resonance imaging of the spinal cord, computed tomography and radiography of the spine, electroneuromyography). The study was conducted at the neurosurgical department of the Republican Children's Clinical Hospital in Ufa between 2014 and 2022. There were 32 implantations of epidural neurostimulators for pelvic organ dysfunctions. RESULTS: Patients used epidural spinal and sacral stimulation up to 6 times a day for 10-15 min turning on the pulse generator. This method significantly increased urinary volume, decreased episodes of urinary leakage and fecal incontinence, residual volume after urination and number of periodic catheterizations compared to baseline data. Sixteen patients were very satisfied, 10 ones were moderately satisfied, and 2 patients were not satisfied with therapy. The number of bladder catheterizations per day decreased by 51.1%. Urine volume significantly increased from 131.5±16.1 to 236±16.7 ml, intravesical pressure decreased from 23.5±4.2 to 18.5±2.1 cm H2O (by 20.3%). CONCLUSION: Chronic epidural spinal and sacral stimulation can improve the quality of life in patients with pelvic organ dysfunction. This technique may be effective for pelvic organ dysfunction caused by myelodysplasia.

Pathways and parameters of sacral neuromodulation in rats.

The stimulation paradigm for sacral neuromodulation has remained largely unchanged since its inception. We sought to determine, in rats, whether stimulation-induced increases in bladder capacity correlated with the proportion of sensory pudendal (PudS) neurons at each stimulated location (L6, S1). If supported, this finding could guide the choice of stimulation side (left/right) and level (S2, S3, S4) in humans. Unexpectedly, we observed that acute stimulation at clinically relevant (low) amplitudes [1-1.5 × motor threshold (Tm)], did not increase bladder capacity, regardless of stimulus location (L6 or S1). More importantly for the ability to test our hypothesis, there was little anatomic variation, and S1 infrequently contributed nerve fibers to the PudS nerve. During mapping studies we noticed that large increases in PudS nerve activation occurred at amplitudes exceeding 2Tm. Thus, additional cystometric studies were conducted, this time with stimulation of the L6-S1 trunk, to examine further the relationship between stimulation amplitude and cystometric parameters. Stimulation at 1Tm to 6Tm evoked increases in bladder capacity and decreases in voiding efficiency that mirrored those produced by PudS nerve stimulation. Many animal studies involving electrical stimulation of nerves of the lower urinary tract use stimulation amplitudes that exceed those used clinically (∼1Tm). Our results confirm that high amplitudes generate immediate changes in cystometric parameters; however, the relationship to low-amplitude chronic stimulation in humans remains unclear. Additional studies are needed to understand changes that occur with chronic stimulation, how these changes relate to therapeutic outcomes, and the contribution of specific nerve fibers to these changes.NEW & NOTEWORTHY Acute low-amplitude electrical stimulation of sacral nerve (sacral neuromodulation) did not increase bladder capacity in anesthetized CD, obese-prone, or obese-resistant rats. Increasing stimulation amplitude correlated with increases in bladder capacity and pudendal sensory nerve recruitment. It is unclear how the high-amplitude acute stimulation that is commonly used in animal experiments to generate immediate effects compares mechanistically to the chronic low-amplitude stimulation used clinically.

Development of a predictive tool for sacral nerve modulation implantation in the treatment of non-obstructive urinary retention and/or slow urinary stream: a study from the Neuro-Urology Committee of the French Association of Urology.

PURPOSE: This study aimed to seek predictive factors and develop a predictive tool for sacral nerve modulation (SNM) implantation in patients with non-obstructive urinary retention and/or slow urinary stream (NOUR/SS). METHODS: This study was designed as a retrospective study including all patients who have undergone a two-stage SNM for NOUR/SS between 2000 and 2021 in 11 academic hospitals. The primary outcome was defined as the implantation rate. Secondary outcomes included changes in bladder emptying parameters. Univariate and multivariable logistic regression analysis were performed and determined odds ratio for IPG implantation to build a predictive tool. The performance of the multivariable model discrimination was evaluated using the c-statistics and an internal validation was performed using bootstrap resampling. RESULTS: Of the 357 patients included, 210 (58.8%) were finally implanted. After multivariable logistic regression, 4 predictive factors were found, including age (≤ 52 yo; OR = 3.31 CI95% [1.79; 6.14]), gender (female; OR = 2.62 CI95% [1.39; 4.92]), maximal urethral closure pressure (≥ 70 cmH2O; OR: 2.36 CI95% [1.17; 4.74]), and the absence of an underlying neurological disease affecting the lower motor neuron (OR = 2.25 CI95% [1.07; 4.76]). Combining these factors, we established 16 response profiles with distinct IPG implantation rates, ranging from 8.7 to 81.5%. Internal validation found a good discrimination value (c-statistic, 0.724; 95% CI 0.660-0.789) with a low optimism bias (0.013). This allowed us to develop a predictive tool ( https://predictivetool.wixsite.com/void ). CONCLUSION: The present study identified 4 predictive factors, allowing to develop a predictive tool for SNM implantation in NOUR/SS patients, that may help in guiding therapeutic decision-making. External validation of the tool is warranted.