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Importance: Sacral neuromodulation (SNM) is an effective treatment for fecal incontinence (FI). Previous studies found that Black women undergo SNM for urinary incontinence less than White women, but there is less known about racial disparities for FI., Objective: This study assessed differences in Black and White patients' FI treatment; SNM counseling was the primary outcome., Study Design: This was a retrospective cohort study of adult non-Hispanic Black and White patients who received FI treatment at an academic institution from 2011 to 2021. Medical records were queried for treatments, testing, and treating specialties for a 2:1 age-matched cohort of White:Black patients., Results: Four hundred forty-seven women were included: 149 Black women and 298 age-matched White women. A total of 24.4% (109) of patients had documented SNM counseling, significantly fewer in Black patients (14.8% vs 29.2%, P < 0.001). A total of 5.1% (23) of patients received SNM, less frequent in Black patients (2.7% vs 6.4%, P = 0.003). Among patients with SNM counseling, there was no difference between cohorts. Black patients were less likely to be referred for physical therapy (59.7% vs 77.2%, P < 0.001), sphincter imaging (0.7% vs 5.7%, P = 0.011), and defecography (8.1% vs 17.1%, P = 0.009). Different specialties managed the 2 cohorts. Black patients were less likely to see urogynecology and colorectal surgery (21.5% vs 34.6%, P = 0.004; 9.4% vs 15.4%, P = 0.077). Patients seen by these surgeons were more likely to discuss SNM (48.6% vs 8.5%, P < 0.001)., Conclusions: There were differences between Black and White patients' FI treatment, including counseling about SNM. Multidisciplinary work is needed to provide equitable education for this life-altering condition., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2024 American Urogynecologic Society. All rights reserved.)

Background: Organophosphate-Induced Delayed Neuropathy (OPIDN) is a rare neurological disorder triggered by exposure to organophosphorus compounds. These compounds exert their neurotoxic effects by impacting the nervous system, leading to systemic manifestations. Urinary system symptoms are infrequently observed in clinical settings. Currently, effective therapeutic interventions for OPIDN-related urinary symptoms are lacking. Sacral nerve modulation therapy, an FDA-approved approach for managing lower urinary tract symptoms, presents as a promising option. Herein, we present a case of OPIDN-induced lower urinary tract obstruction successfully treated with sacral nerve modulation therapy, resulting in substantial symptom relief., Case Report: A 27-year-old male patient presented with severe bilateral hydronephrosis, attributed to low bladder compliance and accompanied by a fever persisting for 6 days. The patient's medical history revealed accidental ingestion of organophosphate pesticide (Dimethoate) with no concomitant underlying diseases. In consideration of the potential for OPIDN, surgical intervention in the form of sacral neuromodulation (phase I) was undertaken. Subsequent evaluation one month post-surgery revealed notable improvements in both bladder compliance and bilateral hydronephrosis, necessitating sacral neuromodulation (phase II). Presently, following a 5-month follow-up period, the patient remains asymptomatic and in favorable health., Conclusion: This patient achieved long-term relief using sacral neuromodulation., (© 2024. The Author(s).)

Competing Interests: Declaration of competing interest The authors declare no competing interests.

Aims: There is limited evidence to support the efficacy of sacral neuromodulation (SNM) for older adults with overactive bladder (OAB). This study aims to report outcomes following SNM among nursing home (NH) residents, a vulnerable population with high rates of frailty and comorbidity., Methods: This is a retrospective cohort study of long-stay NH residents who underwent a trial of percutaneous nerve evaluation (PNE) or Stage 1 permanent lead placement (Stage 1) between 2014 and 2016. Residents were identified using the Minimum Data Set linked to Medicare claims. The primary outcome of this study was successful progression from trial to implant. Rates of 1-year device explant/revisions were also investigated., Results: Trial of SNM was observed in 1089 residents (mean age: 77.9 years). PNE was performed in 66.9% of residents and 33.2% underwent Stage 1. Of Stage 1 procedures, 23.8% were performed with simultaneous device implant (single-stage). Overall, 53.1% of PNEs and 72.4% of Stage 1 progressed to device implant, which was associated with Stage 1 procedure versus PNE (adjusted relative risk [aRR]: 1.34; 95% confidence interval [95% CI]: 1.21-1.49) and female versus male sex (aRR: 1.26; 95% CI: 1.09-1.46). One-year explant/revision was observed in 9.3% of residents (6.3% for PNE, 10.5% for Stage 1, 20.3% single-stage). Single stage procedure versus PNE was significantly associated with device explant/revision (aRR: 3.4; 95% CI: 1.9-6.2)., Conclusions: In this large cohort of NH residents, outcomes following SNM were similar to previous reports of younger healthier cohorts. Surgeons managing older patients with OAB should use caution when selecting patients for single stage SNM procedures., (© 2024 Wiley Periodicals LLC.)

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., (© 2024 The Author(s). Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

Background: Sacral neuromodulation (SNM) is an effective approach for treating lower urinary tract dysfunction (LUTD), and stimulation programming is essential for successful treatment. However, research on SNM programming for various indications is limited. Thus, the authors aimed to determine whether there were differences in the stimulation parameters for different SNM indications and the appropriate programming recommendations., Materials and Methods: Clinical data were retrospectively collected from patients with LUTD who underwent SNM and completed internal pulse generator implantation. The parameters with the highest patient satisfaction or the most symptom improvement during the test period were considered optimal and used to set the programming after internal pulse generator implantation., Results: After screening, 282 patients were enrolled and categorized into four groups based on the following indications: refractory overactive bladder (OAB) ( n =61), neurogenic lower urinary tract dysfunction (nLUTD) ( n =162), interstitial cystitis/painful bladder syndrome (IC/BPS) ( n =24), and idiopathic nonobstructive urinary retention (NOUR) ( n =35). When analyzing the optimal stimulus parameters, disparities in the stimulation amplitude and pulse frequency were noted among the four groups. The stimulation amplitude in the nLUTD group was higher than that in the idiopathic NOUR group ( P =0.013). Differences in pulse frequency were observed between the refractory OAB and nLUTD groups ( P <0.001) and between the refractory OAB and idiopathic NOUR groups ( P =0.001). No differences in the electrode configuration or pulse width settings existed among the four groups., Conclusions: The stimulation parameters for SNM varied among the different indications. For the initial programming of stage I, most patients are recommended to start with stimulation amplitudes below 2 V, although patients with nLUTD may benefit from higher amplitudes. A standard pulse width of 210 μs is recommended for all patients. However, for individuals experiencing nLUTD or idiopathic NOUR, the pulse frequency can begin above the standard 14 Hz but not exceed 50 Hz., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background & Aims: The enteric nervous system (ENS), the gut's intrinsic nervous system critical for gastrointestinal function and gut-brain communication, is believed to mainly originate from vagal neural crest cells (vNCCs) and partially from sacral NCCs (sNCCs). Resolving the exact origins of the ENS is critical for understanding congenital ENS diseases but has been confounded by the inability to distinguish between both NCC populations in situ. Here, we aimed to resolve the exact origins of the mammalian ENS., Methods: We genetically engineered mouse embryos facilitating comparative lineage-tracing of either all (pan-) NCCs including vNCCs or caudal trunk and sNCCs (s/tNCCs) excluding vNCCs. This was combined with dual-lineage tracing and 3-dimensional reconstruction of pelvic plexus and hindgut to precisely pinpoint sNCC and vNCC contributions. We further used coculture assays to determine the specificity of cell migration from different neural tissues into the hindgut., Results: Both pan-NCCs and s/tNCCs contributed to established NCC derivatives but only pan-NCCs contributed to the ENS. Dual-lineage tracing combined with 3-dimensional reconstruction revealed that s/tNCCs settle in complex patterns in pelvic plexus and hindgut-surrounding tissues, explaining previous confusion regarding their contributions. Coculture experiments revealed unspecific cell migration from autonomic, sensory, and neural tube explants into the hindgut. Lineage tracing of ENS precursors lastly provided complimentary evidence for an exclusive vNCC origin of the murine ENS., Conclusions: sNCCs do not contribute to the murine ENS, suggesting that the mammalian ENS exclusively originates from vNCCs. These results have immediate implications for comprehending (and devising treatments for) congenital ENS disorders, including Hirschsprung's disease., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the efficacy and safety of sacral neuromodulation (SNM) in patients with underlying neurologic conditions and compare outcomes to non-neurogenic patients., Methods: Between 2017-2022 patients undergoing 2-staged implantation of InterStim II were included in a single-center retrospective study. Patients were allocated into two groups: underlying neurologic conditions (group 1) or non-neurogenic (group 2). Efficacy and safety were evaluated by comparing patients' bladder/bowel logs pre- and post-operative. Patients' demographics, indications, preimplantation urodynamic study variables, surgery duration, number of postop visits, and time to revision/removal procedures were compared and included in the data analysis., Results: Sixty-seven patients (64.2% female) with a mean age of 63.23 ± 14.15years were included in the study - 16/67(23.9%) patients assigned to group 1. There is no statistically significant difference between the groups regarding the indication for the treatment. The most common indication was nonobstructing urinary retention (NOUR) in both study groups. The common neurologic pathologies were multiple sclerosis, disc disease, and spinal stenosis. Overall and subgroup (based on an indication for SNM implantation) analyses showed no significant difference in patients' demographics, the surgery duration, or the chances for clinical success with a similar follow-up period. During the follow-up, the device was removed in 4 (25.0%) and 10 (19.6%) of the patients in group 1 and group 2, respectively (P = .912). There was no significant difference between the groups in the time till InterStim II removal (P = .905). All NOUR patients with clinical success in group 1 had an improvement of at least 75% from the baseline compared to 69% of patients in group 2 (P = .42). Univariate analysis in NOUR patients demonstrated that maximal cystometric capacity below 430 mL and the presence of detrusor contraction at voiding were statistically significant predictors of successful SNM. Overall, at the end of the follow-up period, 8 (50.0%) and 29 (56.9%) patients in groups 1 and 2, respectively, were defined as clinical success (P = .775)., Competing Interests: Declaration of Competing Interest Michael Vainrib is a consultant for Medtronic Inc (lectures and tutoring). All other authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Inability to remain motionless owing to pain during magnetic resonance imaging (MRI) may increase the need for sedation and analgesia. Here, we present a case where ultrasound-guided sacral erector spinae plane block (ESPB) was used successfully for pain management during an MRI in a patient suffering from severe sacral pain. Sacral ESPB was performed with a total of 30 mL of 0.25% bupivacaine at the level of the intermediate sacral crest. The patient achieved sensory block in the L5-S4 dermatomes without motor block, resulting in complete pain relief. This case report highlights the feasibility of ultrasound-guided sacral ESPB as a potential pain management technique., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 International Anesthesia Research Society.)

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., (© 2024 The Authors. Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

Objective: Sacral neuromodulation (SNM) has emerged as an effective therapy for refractory lower urinary tract dysfunction (LUTD). Remote programming holds promise in addressing the time and economic burdens associated with outpatient programming, especially for patients in the observation period following Stage I implant surgery (where the lead is implanted first without the pulse generator). The study aimed to explore the effectiveness and patient satisfaction of remote programming for Stage I SNM patients, and analyze the benefits patients gain from remote programming., Methods: This prospective study was conducted at multiple high-level clinical SNM centres in China. Patients requiring SNM implantation were enroled and divided into two groups based on patient preference: remote programming (RP) group and outpatient control (OC) group. Patient attitudes toward RP were assessed through questionnaires, and the degree of symptom improvement was compared between the two groups to explore the usability of RP., Results: A total of 63 participants from 6 centres were included in the study, with 32 belonging to the RP group. The remote programming system presents a high level of usability (98%) and willingness (satisfaction rate: 96.83%) in result of questionnaire. RP showed a significant advantage in improving patients' score of ICSI/ICPI (medianΔICSI/ICPI RP vs. OC= -13.50 vs -2, P =0.015). And slightly ameliorate urinary symptoms such as pain (medianΔVAS RP vs. OC= -1 vs 0, P = 0.164) and urgency (medianΔOBASS -2.5 vs. -1, P = 0.,229), but the difference was not statistically significant. RP did not significantly impact the quality of life of patients ( P =0.113), so do the rate of phase-two conversion ( P = 0.926) or programming parameters., Conclusion: To the best of our knowledge, the presented study is the first multicenter research focusing on the remote programming of Stage I SNM patients. Through the clinical implementation and patient feedback, we demonstrate that remote programming is not inferior to in-person programming in terms of success rate, effectiveness, safety, and patient satisfaction., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

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., (© 2024 The Authors. Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

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., Competing Interests: Conflict of Interest Colin Goudelocke is a paid consultant for Medtronic. Julia P. Slopsema, Lisa M. Jungbauer Nikolas, Katie C. Bittner, Anne E. Miller, and Sarah J. Offutt are employees of Medtronic., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Sacral neuromodulation (SNM) is a common treatment for patients with urinary and faecal incontinence. A close contact of the tined lead electrode with the targeted nerve is likely to improve functional outcome. The aim of this study was to compare the position of the SNM lead in relation to the sacral nerve by comparing different implantation techniques., Methods: This cadaver study was conducted at the Division of Anatomy of Vienna's Medical University in October 2020. We dissected 10 cadavers after bilateral SNM lead implantation (n = 20), using two different standardized implantation techniques. The cadavers were categorized as group A (n = 10), representing the conventional guided implantation group and group B (n = 10), where SNM implantation was conducted with the novel fluoroscopy-guided "H"-technique. The primary goal was to assess the distance between the sacral nerve and the lead placement., Results: The electrodes were inserted at a median angle of 58.5° (46-65°) in group A and 60° (50-65°) in group B, without reaching statistical significance. In 8 cadavers, the lead entered the S3 foramen successfully. The median distance of the lead to the nerve did not show a significant difference between both groups (E0: Group A: 0.0 mm vs. Group B: 0.0 mm, p = 0.969; E1: Group A: 0.0 mm vs. Group B: 0.5 mm p = 0.754; E2: Group A: 2.5 mm vs. Group B: 2.5 mm p = 1.000; E3: Group A: 3.5 mm vs. Group B: 4.0 mm p = 0.675). In 2 cases (20%) of the conventional group A, the lead was misplaced and located at the gluteal muscle. Perforation of the presacral fascia was observed in one lead placement in group A and in two placements in group B., Conclusions: Both standardized implantation techniques may ensure close electrode proximity to the targeted nerve. Misplacement of the electrode was more often observed with the conventional implantation technique., (© 2022. The Author(s).)

Aim: Sacral nerve modulation (SNM) is recommended as a first-line surgical therapy for patients with faecal incontinence (FI). During patient follow-up, it is recommended that stimulation settings be reprogrammed to optimize patient outcomes. The aim of the present study was to evaluate the efficacy of stimulator reprogramming in patients with an implanted SNM device to treat FI., Method: The data from patients who received a permanent SNM implant in a single centre from January 2008 to December 2019 were retrospectively analysed. Symptoms that occurred after implantation, the stimulator settings of the SNM device and changes made at each follow-up visit were noted. The efficacy of reprogramming was determined by assessing patient satisfaction., Results: Of the 117 patients (male/female 4/113; mean age 59.5 ± 11.8 years) with a SNM implant for FI, 84 (72%) had at least one symptom requiring reprogramming of the stimulator, most often during the first year after implantation (p = 0.05). The most frequently reported symptoms were loss of efficacy (68.5%; p = 1 × 10 -3 ) and pain (20.5%; p = 1 × 10 -3 ). Reprogramming was effective 53% of the time when treating loss of efficacy and 76% of the time when treating pain. When the stimulation parameters were reprogrammed at least four consecutive times to correct a symptom, the reprogramming was less effective in treating the symptom (p = 0.02)., Conclusion: Regular follow-up of patients with SNM device implants associated with reprogramming of stimulation parameters to improve the treatment of reported symptoms would optimize the efficacy of SNM., (© 2022 The Association of Coloproctology of Great Britain and Ireland.)

Background: The current approach to performing sacral neuromodulation consists of a two-stage procedure, the first of which includes insertion of the sacral electrode under fluoroscopic visualization of the S3 foramen. Alternatively, in certain situations computed tomography (CT)-guided insertion can be used., Objectives: To evaluate the use of CT in cases of reinsertion of the electrode due to infection, dislocation, or rupture., Methods: Medical records of patients who underwent neuromodulation device reinsertion between 2005 and 2016 for fecal incontinence were reviewed. Study outcomes included procedure course, successful placement, and long-term treatment success., Results: During the study period, we inserted a neuromodulation device in 67 patients. A CT-guided insertion of a sacral electrode was performed in 10 patients. In nine patients, the insertion and the final location of the electrode were successful. In one patient, the electrode migrated upward due to a malformation of the S3 foramen on both sides and had to be placed in S4. In a mean follow-up of 68.4 ± 30.0 months following the re-insertion, there was a significant reduction in the number of incontinence episodes per day (P < 0.001) and the number of pads used per day (P = 0.002)., Conclusions: CT-guided insertion of a sacral electrode is a safe and promising option, especially in recurrent and or selected cases.

Objective: To analyze and quantify sacral spinal excitability through bulbocavernosus reflex (BCR) stimulus-response curves., Methods: Thirty subjects with upper motor neuron lesions (UMN) and nine controls were included in this prospective, monocentric study. Sacral spinal excitability was assessed using stimulus-response curves of the BCR, modeled at different bladder filling volumes relative to the desire to void (as defined by the International Continence Society) during a cystometry. Variations in α (i.e. the slope of the stimulus-response curve) were considered as an indicator of the modulation of sacral spinal excitability., Results: In all subjects, α increased during bladder filling suggesting the modulation of spinal sacral excitability during the filling phase. This increase was over 30% in 96.7% of neurological subjects and 88.9% of controls. The increase was higher before the first sensation to void in the neurological population (163.15%), compared to controls, (29.91%), p < 0.001., Conclusions: We showed the possibility of using BCR stimulus-response curves to characterize sacral spinal response with an amplification of this response during bladder filling as well as a difference in this response amplification in patients with UMN in comparison with a control group., Significance: BCR, through stimulus-response curves, might be an indicator of pelvic-perineal exaggerated reflex response and possibly a tool for evaluating treatment effectiveness., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: Spinal perineural Tarlov's cysts (TCs) are considered incidental findings that occasionally might exert pressure upon nerve roots and correspond with patients' signs and symptoms. Purpose of this meta-analysis is to deliver global incidence and characteristics (location, size, and shape) of TCs., Methods: Following PRISMA checklist, all major databases were searched by two authors for radiologic studies reporting incidence and morphologic features (location, size, and shape) of TCs. Anatomical Quality Assessment tool was applied for risk of bias evaluation. Meta-analysis of random-effects model was employed. Subgroup analysis for regional distribution, gender, sacral levels, age, correspondence with symptoms, and persistent genital arousal disorder (PGAD) were planned ahead., Results: 22 radiologic studies of level 3 evidence involving 13,266 subjects were included. Global pooled prevalence of TCs was 4.18% (95% CI 2.47-6.30). Mean pooled sagittal diameter was 11.86 mm (95% CI 10.78-12.93). Sacral cysts strongly prevailed over the other segments. Of the sacral, S2 level was the most common (46.7% [95% CI 29.4-60.5]). Geographically, the highest incidence was found in Europe (6.07% [95% CI 1.49-13.00]), followed by North America (3.82% [95% CI 0.49-9.44]), and Asia (3.33% [95% CI 1.52-5.75]). TCs were more common in women than in men (5.84% vs 3.03%, p < 0.001, test of homogeneity, χ 2 ). Subjects with PGAD had incidence of 37.87% (95% CI 2.45-81.75). TCs in pediatric population are rare-0.53% (95% CI 0.02-1.51). 15.59% of TCs corresponded with symptoms., Conclusions: Spinal perineural (Tarlov) cysts are found in a minority of population. S2 level of the sacral bone is affected most frequently. There is female predominance. Correspondence with symptoms is seen in less than one-fifth of TCs. Studies with stronger evidence level are needed to corroborate the results. The purported high incidence in PGAD requires confirmation in case-control studies for the risk-ratio calculation.

Storage and voiding of urine from the lower urinary tract (LUT) must be timed precisely to occur in appropriate behavioral contexts. A major part of the CNS circuit that coordinates this activity is found in the lumbosacral spinal cord. Immediate early gene (IEG) activity mapping has been widely used to investigate the lumbosacral LUT-related circuit, but most reports focus on the effects of noxious stimulation in anesthetized female rats. Here we use c-Fos and EGR-1 (Zif268) activity mapping of lumbosacral spinal cord to investigate cystometry-induced micturition in awake female and male rats. In females, after cystometry c-Fos neurons in spinal cord segments L5-S2 were concentrated in the sacral parasympathetic nucleus (SPN), dorsal horn laminae II-IV, and dorsal commissural nucleus (SDCom). Comparisons of cystometry and control groups in male and female revealed sex differences. Activity mapping suggested dorsal horn laminae II-IV was activated in females but showed net inhibition in males. However, inhibition in male rats was not detected by EGR-1 activity mapping, which showed low coexpression with c-Fos. A class of catecholamine neurons in SPN and SDCom neurons were also more strongly activated by micturition in females. In both sexes, most c-Fos neurons were identified as excitatory by their absence of Pax2 expression. In conclusion, IEG mapping in awake male and female rats has extended our understanding of the functional molecular anatomy of the LUT-related circuit in spinal cord. Using this approach, we have identified sex differences that were not detected by previous studies in anesthetized rats., (© 2020 The Authors. The Journal of Comparative Neurology published by Wiley Periodicals, Inc.)

Two female patients aged 70 and 72 with video-urodynamics-confirmed detrusor overactivity and detrusor underactivity (DO-DU) were treated. Patients were refractory to medical therapies and had previously failed intravesical botulinum toxin type A (BoNT-A) at other centers secondary to urinary retention and difficulty with self-catheterization. Placement of an Interstim II device (Medtronic, Minneapolis, Minnesota) for sacral neuromodulation (SNM) as alternative third-line treatment partially improved overactive bladder (OAB) symptoms while significantly improving voiding symptoms. Postvoid residual (PVR) of patients improved from a median of 118 mL (110-125 mL) to 20 mL (18-26 mL) and 213 mL (195-230 mL) to 70 mL (60-73 mL), respectively. Addition of medical therapies post SNM failed to modify OAB symptoms further and a rechallenge with dose-reduced BoNT-A was undertaken.OAB symptoms were significantly improved by addition of BoNT-A, while urinary retention was avoided (median PVR post BoNT-A 38 mL [34-40 mL] and 185 mL [150-205 mL], respectively). Reduction in incontinence pad use as well as resolution of nighttime incontinence in both patients and daytime incontinence in one patient was achieved. DO-DU patients treated by SNM who have improved bladder emptying (PVR <100 mL) but incomplete resolution of OAB symptoms should be trialed on adjunct medical therapies to improve OAB symptoms. If OAB symptoms are still inadequately controlled, consideration of a rechallenge with BoNT-A, particularly with dose reduction, appears to be efficacious and avoids symptomatic retention in this challenging cohort., (© 2020 John Wiley & Sons Australia, Ltd.)

Introduction: Transcutaneous parasacral nerve stimulation (TPNS) via electrodes placed over the sacrum can activate afferent neuronal networks noninvasively, leading to sacral reflexes that may improve colonic motility. Thus, TPNS can be considered a promising, noninvasive, and safe method for the treatment of constipation. However, there is no published study investigating its use in children with functional constipation. This is a single-center, prospective, longitudinal, and interventional study designed to assess the applicability and clinical outcomes of TPNS in functionally constipated children., Patient Concerns: Parents or guardians of patients will be informed of the purpose of the study and will sign an informed consent form. The participants may leave the study at any time without any restrictions., Diagnosis: Twenty-eight children (7-18 years old) who were diagnosed with intestinal constipation (Rome IV criteria) will be included., Interventions: The patients will be submitted to daily sessions of TPNS for a period of 4 or 8 weeks and will be invited to participate in semistructured interviews at 3 or 4 moments: 1 week before the beginning of TPNS; immediately after the 4 and/or 8 weeks of TPNS; and 4 weeks after the end of the intervention period. In these appointments, the aspects related to bowel habits and quality of life will be assessed., Outcomes: This study will evaluate the increase in the number of bowel movements and stool consistency, the decrease in the number of episodes of retentive fecal incontinence, and the indirect improvement in the overall quality of life., Conclusion: we expect that this study protocol can show the efficacy of this promising method to assist the treatment of children with functional constipation., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc.)

Spinal cord injury (SCI) often leads to defecation dysfunction. Sacral nerve electrical stimulation (SNS) therapy could improve defecation function. The present study aimed to assess SNS therapy, with regard to the levels of serotonin (5‑HT) and its receptors (5‑HT3AR and 5‑HT4R) in the colon and sacral cord, a rat model of acute severe SCI was used. This rat model was made using the New York University Impactor device. Model rats were randomized to the SCI and SNS (electrical stimulation on the S3 nerve) groups. After 14 days of treatment, enteric transmission function was assessed. 5‑HT and 5‑HT3AR/5‑HT4R were measured by ELISA, quantitative PCR, immunohistochemistry and western blotting. In SCI rats, SNS significantly increased the quantity of feces, shortened the time to the first fecal passage, and improved fecal texture and colon histology. SNS elevated 5‑HT contents in the colon and spinal cord, and enhanced 5‑HT3AR/5‑HT4R protein expression and distribution in the colonic myenteric plexus and mucosa, sacral intermediolateral nucleus and dorsal horn. SNS upregulated the relative expression levels of 5‑HT3AR/5‑HT4R mRNA and protein in the colon and spinal cord. SNS can improve defecation and accelerate the recovery of colonic transmission functions in rat models of acute SCI. These effects involved upregulation of the 5‑HT/5‑HT3AR/5‑HT4R axes.

Inflammatory bowel disease (IBD) is a common chronic inflammatory disease of the digestive tract that is often debilitating. It affects patients' quality of life and imposes a financial burden. Despite advances in treatment with medications such as biologics, a large proportion of patients do not respond to medical therapy or develop adverse events. Therefore, alternative treatment options such as electrical neuromodulation are currently being investigated. Electrical neuromodulation, also called bioelectronic medicine, is emerging as a potential new treatment for IBD. Over the past decade, advancements have been made in electrical neuromodulation. A number of electrical neuromodulation methods, such as vagus nerve stimulation, sacral nerve stimulation, and tibial nerve stimulation, have been tested to treat IBD. A series of animal and clinical trials have been performed to evaluate efficacy with promising results. Although the exact underlying mechanisms of action for electrical neuromodulation remain to be explored, this modality is promising. Further randomized controlled trials and basic experiments are needed to investigate efficacy and clarify intrinsic mechanisms., (© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Descending neuromodulators from the brainstem play a major role in the development and regulation of spinal sensorimotor functions. Here, the contribution of serotonergic signaling in the lumbar spinal cord was investigated in the context of the generation of locomotor activity. Experiments were performed on in vitro spinal cord preparations from newborn rats (0-5 days). Rhythmic locomotor episodes (fictive locomotion) triggered by tonic electrical stimulations (2Hz, 30s) of a single sacral dorsal root were recorded from bilateral flexor-dominated (L2) and extensor-dominated (L5) ventral roots. We found that the activity pattern induced by sacral stimulation evolves over the 5 post-natal (P) day period. Although alternating rhythmic flexor-like motor bursts were expressed at all ages, the locomotor pattern of extensor-like bursting was progressively lost from P1 to P5. At later stages, serotonin (5-HT) and quipazine (5-HT2A receptor agonist) at concentrations sub-threshold for direct locomotor network activation promoted sacral stimulation-induced fictive locomotion. The 5-HT2A receptor antagonist ketanserin could reverse the agonist's action but was ineffective when fictive locomotion was already expressed in the absence of 5-HT (mainly before P2). Although inhibiting 5-HT7 receptors with SB266990 did not affect locomotor pattern organization, activating 5-HT1A receptors with 8-OH-DPAT specifically deteriorated extensor phase motor burst activity. We conclude that during the first 5 post-natal days in rat, serotonergic signaling in the lumbar cord becomes increasingly critical for the expression of fictive locomotion. Our findings therefore further underline the importance of both descending serotonergic and sensory afferent pathways in shaping locomotor activity during postnatal development. This article is part of the special issue entitled 'Serotonin Research: Crossing Scales and Boundaries'., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Most of knowledge on muscle radicular innervation was from explorations in root/spinal cord pathologies. Direct and individual access to each of the lumbar-sacral -ventral and dorsal- nerve roots during dorsal rhizotomy for spastic diplegia allows precise study of the corresponding muscle innervation. Authors report the lumbo-sacral segmental myotomal organization obtained from recordings of muscle responses to root stimulation in a 20-children prospective series., Methods: Seven key-muscles in each lower limb and anal sphincter were Electromyography (EMG)-recorded and clinically observed by physiotherapist during L2-to-S2 dorsal rhizotomy. Ventral roots (VR), for topographical mapping, and dorsal roots (DR), for segmental excitability testing, were stimulated, just above threshold for eliciting muscular response., Results: In 70% of the muscles studied, VR innervation was pluri-radicular, from 2-to-4 roots, with 1 or 2 roots being dominant at each level. Overlapping was important. Muscle responses to DR stimulation were 1.75 times more extended compared to VR stimulation. Inter-individual variability was important., Conclusions: Accuracy of root identification and stimulation with the used method brings some more precise information to radicular functional anatomy., Significance: Those neurophysiological findings plead for performing Intra-Operative Neuromonitoring when dealing with surgery in the lumbar-sacral roots., Competing Interests: Declaration of competing interest The authors have no conflict of interest, ethical adherence and any financial disclosures., (Copyright © 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

The objective of this review was to compare the efficacy and safety of conservative surgery with or without adjunctive presacral neurectomy (PN) for chronic endometriosis-related pelvic pain. In a systematic review with meta-analysis, randomized or nonrandomized controlled studies of conservative endometriosis surgery with or without adjunctive PN were included. Main outcomes were treatment failure (the proportion of women in which surgery failed to adequately resolve midline pain) and the frequency of operative and postoperative complications. A total of 7 studies with 8 group comparisons (3 randomized) representing 503 women (250 PN; 253 Control) were included. Over 34 months median follow-up, crude rates of treatment failure were 15.0% with PN and 40.9% with Controls (risk ratio = 0.43, 95% CI = 0.30 to 0.60, p < 0.001). The risk of postoperative constipation was higher with PN vs. Controls (12.5% vs. 0%, p = 0.024). No treatment group differences were observed for the risk of operative complications (0.6% vs. 0%, p = 0.498), reoperation (4.1% vs. 3.0%, p = 0.758) or urinary incontinence (5.0% vs. 0%, p = 0.195). Overall, in well-selected patients, conservative surgery with adjunctive PN may provide greater relief from midline pain and a similarly low rate of operative complications relative to conservative surgery alone but may increase the risk of constipation postoperatively. However, results were derived from mainly older and lower quality studies. Since then, surgical techniques to treat endometriosis have been improved and the effect of PN observed in prior studies should be confirmed in future studies in women in whom radical excision of deep infiltrating lesions is obtained.

Rationale: Anterior spinal meningoceles are rare neuroanatomic abnormality formed by protrusion of the spinal meninges through a defect in the vertebral column. Presently, therapeutic options for anterior spinal meningoceles are still controversial. The objective of this study is to discuss the individualized management of giant anterior spinal meningoceles., Patient Concerns and Diagnoses: We analyzed 4 patients with anterior spinal meningoceles between 2007 and 2014 in our department by retrospective chart review, two of whom were anterior sacral meningoceles (ASMs), and another2 were intrathoracic meningoceles (ITMs)., Interventions and Outcomes: Patients mainly presented with compressive symptoms including rectal irritation, dyspnea (patient 3) and fixed neurologic deficits (patient 4). Three out of 4 patients received surgical treatment, one of which underwent reoperation. After surgery, meningoceles in 1 patient completely disappeared. Two patients acquired the stability of the size of the meningoceles., Lessons: Management of anterior spinal meningoceles often requires precise treatment based on the different conditions of each patient. Surgical intervention has been proposed for the treatment of symptomatic anterior spinal meningoceles. The goal of surgery is to safely disconnect the linkage between the cyst and CSF from subarachnoid space to prevent further enlargement of the cyst or reaccumulating of cystic fluid.

Sacral nerve stimulation (SNS) was reported to improve 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. The aim of this study was to investigate whether the SNS anti-inflammatory effect is mediated via the local sacral splanchnic nerve or the spinal afferent-vagal efferent-colon pathway. Under general anesthesia, rats were administrated with TNBS intrarectally, and bipolar SNS electrodes were implanted unilaterally at S 3 . The sacral and vagal nerves were severed at different locations for the assessment of the neural pathway. SNS for 10 days improved colonic inflammation only in groups with intact afferent sacral nerve and vagus efferent nerve. SNS markedly increased acetylcholine and anti-inflammatory cytokines (IL-10) and decreased myeloperoxidase and proinflammatory cytokines (IL-2, IL-17A, and TNF-α) in colon tissues. SNS increased the number of c-fos-positive cells in the brain stem and normalized vagal activity measured by spectral analysis of heart rate variability. SNS exerts an anti-inflammatory effect on TNBS-induced colitis by enhancing vagal activity mediated mainly via the spinal afferent-brain stem-vagal efferent-colon pathway. NEW & NOTEWORTHY Our findings support that there is a possible sacral afferent-vagal efferent pathway that can transmit sacral nerve stimulation to the colon tissue. Sacral nerve stimulation can be carried out by spinal cord afferent to the brain stem and then by the vagal nerve (efferent) to the target organ.

Purpose: Sacral neuromodulation is traditionally performed in 2 stages. Studies have projected that 1-stage sacral neuromodulation is cost-effective if the conversion rate is 61.3% or greater. To our knowledge we present the first case series in the literature to evaluate the cost of 1-stage sacral neuromodulation. The objective of our study was to evaluate outcomes and analyze cost using our institutional experience with 1-stage sacral neuromodulation., Materials and Methods: A total of 15 consecutive 1-stage sacral neuromodulation procedures were performed at a self-insured, integrated health care institution. Cost data were determined using 2019 Medicare reimbursement rates for CPT codes 64581, 64585, 64590 and 64595. Median operative time was derived from actual institutional data., Results: One-stage sacral neuromodulation implantation was performed in 15 patients. Median followup was 14.6 months (IQR 6.9-22.5). Of the 15 cases 14 (93.3%) were successful, defined as a 50% or greater improvement from baseline. Total reimbursement for the 15 patients who underwent 1-stage implantation was $329,430. If these patients had undergone traditional 2-stage implantation with equivalent outcomes, the overall reimbursement was determined to be $414,796. Single-stage sacral neuromodulation implantation provided a calculated total cost savings of $85,366 (p <0.01). Moreover, a projected 233 minutes in operative time was saved by performing 1-stage sacral neuromodulation (p <0.01)., Conclusions: This study demonstrates the potential health care savings of a 1-stage sacral neuromodulation procedure. Moreover, 1-stage sacral neuromodulation may have other added benefits, such as reduced infection rates, patient satisfaction and other indirect cost savings, including reduced time off from work.

Objective: The sacral dorsal rami form the posterior sacrococcygeal plexus (PSCP), which has been scantly studied. This study's goal was to clarify the PSCP s detailed anatomy and discuss its clinical relevance., Methods: Ten sides of 5 fresh-frozen cadavers were dissected for this research. After the muscles covering the sacrum were removed, the PSCP was identified and traced under the operating microscope until the entire plexus was exposed. The contributions to this plexus and its relations to surrounding anatomic structures were recorded., Results: The PSCP was found on all sides and was composed of a medial trunk (MT), communicating branches, and a lateral trunk. Each sacral dorsal ramus's MT formed a series of loops created by adjacent sacral dorsal rami placed between the transverse tubercles and the posterior sacral foramina. The MT, communicating branches, and lateral trunk demonstrated potential entrapment sites., Conclusions: To our knowledge, this is the first anatomic study that provides detailed images that indicate 3 potential sites where surrounding structures could entrap the PSCP. Knowledge of its detailed anatomy might help in better understanding low-back pain, targeting pain sources and guide spine surgeons for avoiding injury to these nerves., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Urgency is a complaint of sudden, compelling desire to pass urine, which is difficult to defer, caused by involuntary contraction of the detrusor muscle during the bladder-filling stage. To enable detrusor inhibition, electrotherapy resources such as transcutaneous tibial nerve stimulation (TTNS) and parasacral transcutaneous electrical stimulation (PTES) have been used. The objective this study is to publish the study protocol that aims to investigate whether urgency decreases after treatment with both of the techniques., Methods: This randomized controlled clinical trial will include 99 women, aged more than 18 years old, with urgency (score ≥ 8 in the Overactive Bladder-Validated 8-Question Awareness Tool [OAB-V8]). Women will be randomly allocated into three groups: TTNS, PTES, and placebo. The following questionnaires will be applied: the Anamnesis Record, the Incontinence Questionnaire Overactive Bladder, the King's Health Questionnaire, the 24-Hour Voiding Diary, and the OAB-V8, at four different time points: at baseline prior to the first session, at the 6th session, the 12th session and at follow-up. The current used for the transcutaneous electrical stimulation will be a symmetrical balanced biphasic pulsed current, for 12 sessions, twice a week, for 20 minutes. Qualitative variables will be displayed as frequency and percentage, quantitative variables as mean and standard deviation. Comparison of urgency severity among groups will be performed with a repeated measures ANOVA, considering the effect of the three groups and the four evaluations, and interactions among them., Discussion: The present study aims to contribute evidence for a more in-depth discussion on electrode positioning for electrostimulation used in urgency treatment. It should be emphasized that, based on the possibility of confirming the hypothesis that urgency will decrease in a similar way after both treatments (TTNS and PTES), the PTES will be used as an option for positioning the electrodes alternatively to the tibial nerve region in special populations, such as amputees or people with severe lower limb sensory impairment., Trial Registration: Brazilian Registry of Clinical Trials (ReBEC) ID: RBR-9rf33n, date of registration: 17 May 2018.

75% of multiple sclerosis (MS) patients have lower urinary tract symptoms. Moreover, up to 80% of asymptomatic patients show abnormalities on urodynamic examination. The objective of this study is to assess the effect of repetitive magnetic stimulation on the motor cortex versus sacral roots in MS patients with lower urinary tract dysfunction (LUTD). 40 MS patients with LUTD were divided according to urodynamic studies (UDS) into two groups (20 patients each): Group A (overactive bladder) and Group B (underactive bladder). Each group was further subdivided into Subgroup (A-I) and (B-I) which received cortical magnetic stimulation and Subgroup (A-II) and (B-II) which received sacral magnetic stimulation. UDS, pelvic ultrasound as well as Incontinence Quality of Life (I-QOL) questionnaire were compared before and after magnetic stimulation sessions in each group as well as between groups. UDS showed significant reduction in bladder capacity, improvement in bladder contractility in all groups and subgroups. Moreover, it showed improvement of urine flow rate only in Group B. Reduction of post-void residual urine was noted in all subgroups except in (Group A-II). I-QOL questionnaire showed improvement in patients with underactive bladder only. Intergroup comparison between A and B showed no difference. Cortical as well as sacral magnetic stimulation showed significant effect on lower urinary tract dysfunction that led to improvement in symptoms in MS patients with underactive bladder, rather than those with overactive bladder.

Objectives: To evaluate the effect of transcutaneous tibial nerve stimulation (TTNS) and transcutaneous parasacral stimulation on the treatment of overactive bladder (OAB) in elderly people and to compare the final results between groups., Methods: Fifty female volunteers, mean age 68.62 (±5.9) years, were randomly allocated into two groups: those receiving TTNS (G1, N=25) and those receiving transcutaneous parasacral stimulation (G2, N=25). The primary outcome was the International Consultation on Incontinence Questionnaire (ICIQ-OAB) score, and secondary outcomes were the International Consultation on Incontinence Questionnaire - short form (ICIQ-SF) score and 3-day bladder diary measurements. Volunteers were assessed before and after the treatment. Clinical Trials (ReBeC): RBR-9Q7J7Y., Results: Both groups' symptoms improved as measured by the ICIQ-OAB (G1 = <0.001; G2 = <0.001) and ICIQ-SF (G1 = <0.001; G2 = <0.001). In the 3-day bladder diary assessments after treatment, G1 showed a reduced number of nocturia (p<0.001), urgency (p<0.001) and urge urinary incontinence episodes (p<0.001), whereas G2 showed only a reduced number of nocturia episodes (p<0.001). No difference between groups was found., Conclusion: Both of the proposed treatments were effective in the improvement of OAB symptoms, but TTNS showed a reduction in a greater number of symptoms as measured by the 3-day bladder diary. No differences were found between groups.

To investigate the efficacy of sacral nerve stimulation (SNS) on nerve growth factor (NGF) mediated visceral sensitivity in normal rat and visceral hypersensitivity model rats. 120 male newborn rats were randomly divided into 6 groups: group A was normal model group; group B ~ F were all sensitized with acetic acid enema and grouped again. Group c2 was given NGF antagonist, d2 group was given NGF agonist, e2 group was given PI3K inhibitor, and f2 group was given PLC-γ inhibitor. After treatment, the expression of NGF, TrKA, PI3K, AKT, PLC-γ, NF-κB, TRPV1, pTRPV1 and intracellular Ca 2+ content were detected. The expression of protein TRPV1 and pTRPV1 was increased, and Ca 2+ was increased in the visceral hypersensitive group. NGF, TrKA in NGF antagonist group, PI3K, AKT, NF-κB in PI3K inhibitor group, PLC-γ in PLC-γ inhibitor group were all almost not expressed. The relative expression of NGF, TrKA, PI3K, AKT, PLC-γ and NF-κB in NGF antagonist group was lower than that in visceral hypersensitivity group and NGF activator group (P < .01). The relative expression of NGF, TrKA, PI3K and AKT mRNA in NGF antagonist group was lower than that in the normal model group (P < .01). There was no significant difference in the relative expression of PLC-γ and NF-κB mRNA (P > .05). The expression level of MAPK, ERK1 and ERK2 in visceral hypersensitivity group was higher than that in PI3K inhibitor group and PLC-γ inhibitor group. The normal group Ca 2+ curve was flat, and the NGF agonist group had the highest Ca 2+ curve peak. Calcium concentration in visceral hypersensitivity group was higher than that in PI3K inhibitor group and that in PLC-γ inhibitor group was higher than that in NGF antagonist group. The binding of TrkA receptor to NGF activates the MAPK/ERK pathway, the PI3K/Akt pathway and the PLC-γ pathway, causing changes in the fluidity of intracellular and extracellular Ca 2+ , resulting in increased sensitivity of visceral tissues and organs., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Aim: Low anterior resection syndrome (LARS) can affect up to 70% of all patients with rectal cancer. In the last two decades, sacral nerve stimulation (SNS) has emerged as an effective treatment for faecal incontinence. There is some encouraging literature on the use of SNS in patients with LARS. The purpose of this review is to provide an up to date review on the utility of SNS on LARS., Method: A literature search was conducted using the MEDLINE, Embase and PubMed databases (January 1981-March 2019). Studies identified were appraised with standard selection criteria. Data points were extracted, and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses., Results: Ten studies met the inclusion criteria and were included in this study. All studies used the Cleveland Clinic Incontinence Score (CCIS), whereas the low anterior resection syndrome score (LARS score) was used in three studies. Overall median improvement in the scoring system was 67.0% (range 35.5%-88.2%) after SNS implantation. There was a significant reduction in CCIS after SNS implantation (mean difference 11.23, 95% confidence interval 9.38-13.07, Z = 11.90, P < 0.00001). The LARS score was also significantly reduced after using SNS in patients with LARS (mean difference 17.87, 95% confidence interval 10.15-25.59, Z = 4.54, P < 0.00001)., Conclusion: Use of SNS may provide symptomatic benefits for patients with LARS refractory to medical therapy. However, the current level of evidence remains limited. A large multicentre study of SNS for LARS using the validated LARS score is warranted. In addition, the cost-effectiveness of SNS for patients with LARS needs further exploration., (Colorectal Disease © 2019 The Association of Coloproctology of Great Britain and Ireland.)

Study Design: Retrospective review of data., Objective: To determine if there is a relationship between the Asia Impairment Scale (AIS) and the bladder and bowel components of the International Standards to Document Remaining Autonomic Function after SCI (ISAFSCI)., Setting: University-Based Academic Rehabilitation Program., Methods: Retrospective cross-sectional study assessing International Standards for Neurologic Classification After SCI (ISNCSCI) examination along with bladder and bowel components of the ISAFSCI., Results: Subjects with AIS A injuries were statistically less likely to have history of bladder control and bowel control per investigator determination and bladder sensation via self-report versus patients categorized with AIS B injuries. Self-reported history of bowel sensation and control of voiding were more likely in subjects with C, D, or E injuries than with B injuries. Bowel and bladder control as determined by investigator and bladder and bowel sensation and control as self-reported were all statistically less likely in persons with AIS A injuries versus CDE., Conclusions: This retrospective study provides initial data regarding components of the bladder and bowel sections of the sacral ISAFSCI and AIS. Further prospective research is needed to further characterize the relationship between retention of bladder and bowel sensation and function and the AIS. We suggest that incorporation of the sacral components of the ISAFSCI into the ISNCSCI may be beneficial to obtain further information about retention of sacral function with specific patterns of injury., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s), under exclusive licence to International Spinal Cord Society 2019.)

Aim: The aim of this study is to evaluate the short- and long-term efficacy of sacral nerve stimulation (SNS) for treating slow-transit constipation (STC)., Method: This is a retrospective cohort analysis of the efficacy of SNS in treating patients affected by STC, who previously failed to respond to conservative therapies. Only patients free of concomitant diseases were enrolled in our study. A temporary stimulation lead was initially implanted; patients with a > 50% symptom reduction were eventually deemed eligible for a permanent implant., Results: This study enrolled 25 patients who underwent a SNS test stimulation; 21 patients (13 women; median age 32 years) eventually got a permanent implant. The median preoperative Cleveland Clinic Constipation Score (CCCS) was 21 (16-25). Preoperative colorectal transit time recorded a median of 10 markers (7-19) retained in the colorectal tract. At 6-month postoperative follow-up, the total number of markers retained in the colorectal tract decreased to 3 (0-4). The CCCS score improved during the first postoperative year (P < 0.001), but progressively worsened over the longer term. The SF-36 questionnaire showed an improvement in all 8 scales measuring physical and psycho-emotional states; all parameters recorded into the bowel diary also improved. Overall, at 60-month follow up, the overall neuromodulator removal rate was 48%., Conclusions: The SNS is a minimally invasive surgical procedure that we tested for treating STC. The short-term outcome was promisingly after 6 months; however, there was a declining trend beyond this interval. Thus, the long-term efficacy of SNS needs to be further assessed.

Background: Sacral nerve stimulation (SNS) is frequently used for constipation and fecal incontinence in the adult literature. The purpose of this study is to perform a systemic review of the literature for SNS for constipation and fecal incontinence in children with emphasis in anorectal malformations., Methods: Systematic literature review was conducted to include all SNS studies in patients < 19 years of age. Studies were separated into those for (1) constipation, (2) bowel and bladder dysfunction, and (3) anorectal malformations., Results: 28 articles were included in the review: (1) 12 constipation (269 patients) and (2) 16 bowel and bladder dysfunction (441 patients). Some studies overlapped groups, as they included some patients with anorectal malformations (4 articles and 29 patients). Constipation studies included slow transit and retention constipation and showed varying degrees of improvement. For bowel and bladder dysfunction, studies also reported varying degrees of improvement using different measures (number of bowel movements per day, transit times, and soiling improvement). There was no specific description of the results in anorectal malformation (ARM) cases and also information regarding specific ARM type, sacral ratio, or presence of tethered cord., Conclusions: SNS for constipation and urinary problems seems to be promising. Data are limited and heterogeneous, and SNS cannot be definitively encouraged or discouraged in patients with ARM, based on current studies. Future studies should include more objective measurements of bowel outcomes and specify outcomes related to patients with anorectal malformations including information regarding their specific malformation, sacral ratio, and presence of tethered cord. Complications' rate is considerable high.

Objectives: Sacral nerve stimulation (SNS) is a surgical treatment of urinary and fecal incontinence. Despite its clinical efficacy, the mechanisms of action of SNS are still poorly known. This may be related to the use of acute stimulation models. Up to date, no rodent model of chronic SNS implants has been developed. Therefore, the aim of this study was to create a fully implantable and remotely controllable stimulating device to establish an animal model of chronic SNS., Materials and Methods: The stimulating device consisted of an implantable pulse generator linked to a platinum electrode. The communication with the device was made through an inductive link which allowed to adjust the stimulation parameters; that is, to turn the device on and off or check the battery status remotely. Rats underwent two surgical procedures. In the first procedure, we achieved chronic sacral stimulation but the implanted electrode was not fixated. In the second procedure, the electrode was fixated in the sacral foramen using dental resin. In both cases, the correct positioning of the electrode was evaluated by computed tomography (CT) imaging and the presence of tail tremor in response to high intensity stimulation. We only tested the function of implanted electrode with fixation using micturition frequency assessment following bipolar or unipolar SNS for three days after recovery., Results: CT imaging showed that implantation of the electrode required fixation as we found that the second surgical procedure yielded a more precise placement of the implanted electrode. The correct placement of implanted electrode observed with imaging was always correlated with a successful tail tremor response in rats, therefore we pursued our next experiments with the second surgical procedure and only assessed the tail tremor response. We found that both bipolar and unipolar SNS reduced micturition frequency., Conclusion: This stimulating device provides an efficient method to perform chronic SNS studies in rats., (© 2018 International Neuromodulation Society.)

Objectives: Incomplete spinal cord injury (SCI) accounts for two-thirds of all SCIs in clinical practice. Preclinical research on the effect of sacral neuromodulation (SNM) on bladder function, however, has been focused only on animal models of complete SCI. We aimed to evaluate the effect of early SNM on bladder responses in a rat model of incomplete SCI., Materials and Methods: Altogether, 21 female Sprague-Dawley rats were equally assigned to control (CTR), SCI + sham stimulation (SHAM), and SCI + SNM (SNM) groups. In the SHAM and SNM groups, incomplete SCI was created by producing a moderate contusion with an NYU-MASCIS impactor at the T9-T10 level of the spine, with needle electrodes implanted bilaterally into the S2 or S3 sacral foramen. Only SNM group underwent electrical stimulation for 28 days, beginning on day 7 after SCI. Cystometry was performed 35 days after SCI., Results: Although the interval between voiding contractions was significantly longer in the SHAM group than the CTR group (25.5 ± 1.4 vs. 12.5 ± 1.7 min; p < 0.05), there were no significant differences between the SNM group (16.5 ± 1.5 min) and the CTR group. Maximum voiding contraction pressure did not differ among the groups. The SNM group had a significantly lower frequency (3.5 ± 0.5 vs. 14.6 ± 2.0; p < 0.05) and maximum pressure (11.4 ± 6.2 vs. 21.3 ± 1.8 cmH 2 O; p < 0.05) of nonvoiding contractions than the SHAM group., Conclusions: Our results provide experimental evidence that early SNM treatment may prevent or diminish bladder dysfunctions (e.g., detrusor overactivity, abnormal micturition reflex) in a clinical condition of incomplete SCI., (© 2018 International Neuromodulation Society.)

Objectives: In rodents, we reported that short pulse-width (PW) neuromodulation might provide more efficient therapy delivery than traditional 0.21 msec PW. Using fully implanted, commercialized systems in the sheep, the goal of this study was to characterize the relationship of electromyographic (EMG) responses of the external anal sphincter (EAS) to different PWs of sacral neuromodulation (SNM)., Materials and Methods: In seven sheep, InterStim® quadripolar tined leads were implanted adjacent to the S3 nerve root bilaterally to deliver SNM and two pairs of intramuscular leads were placed on either side of the EAS for EMG sensing. The EMG responses to SNM with different PWs were examined using variable intensities in both anesthetized and conscious conditions., Results: The EMG responses from ipsilateral EAS (I EAS ) and contralateral EAS (C EAS ) were compared. The area under the curve of EMG responses from I EAS were significantly stronger than that from C EAS. The late component EMGs were more sensitive to nerve stimulation with a higher response amplitude in awake sheep. The response threshold-PW relationship from the I EAS as ascertained visually and with EMG in anesthetized and awake sheep were fitted with a monoexponential nonlinear regression; the resulting chronaxies were of 0.05 msec (n = 6), and 0.04 msec (n = 6), and 0.04 msec (n = 8), respectively., Conclusions: In both anesthetized and awake conditions, a similar motor response may be evoked in the EAS at PWs much shorter (0.04-0.05 msec) than the 0.21 msec typically used with SNM. Potential battery savings manifested by shorter PW would provide more efficient therapy delivery and increased longevity of the stimulator., (© 2018 International Neuromodulation Society.)

Purpose: This five-year, retrospective, multicenter study evaluated the long-term safety and efficiency of sacral neuromodulation (SNM) in Chinese patients with urinary voiding dysfunction., Patients and Methods: This is a Chinese national, multicenter, retrospective study that included 247 patients (51.2% female) who received an implantable pulse generator (IPG) (InterStim, Medtronic, Minneapolis, MN, USA) between 2012 and 2016. Success was considered if the initial ≥50% improvement in any of primary voiding diary variables persisted compared with baseline. The results were further stratified by identifying patients who showed >50% improvement and those although showed <50% improvement but still wanted to receive IPG; these data were collected and analyzed for general improvement., Results: Following test stimulation, 187 patients (43%) declined implantation and 247 (57%) underwent implantation using InterStim®. Among 247 patients, 34 (13.7%) had overactive bladder (OAB), 59 (23.8%) had interstitial cystitis/bladder pain syndrome (IC/BPS), 47 (19%) had idiopathic urinary retention (IUR), and 107 (44.1%) had neurogenic bladder (NB). IPG efficiency rate for OAB, interstitial cystitis/bladder pain syndrome, idiopathic urinary retention, and neurogenic bladder were 42.5, 72.4, 51.6, and 58.8%, respectively. The mean duration of follow-up was 20.1 ± 12.8 months., Conclusions: SNM appears effective in the long term, with a total IPG implantation rate of approximately 57% (ranging between 42.5 and 72.4% depending on indication). Interstitial cystitis/bladder pain syndrome appear to be the best indication for stage I testing. Chinese neurogenic bladder patients are most inclined to choose SNM. SNM is relatively safe, with low postoperation adverse events of 16.1% and reoperation rate of 3.2% during the follow-up period., (© 2019 International Neuromodulation Society.)

Background: Lead placement within the sacral foramen in sacral neuromodulation patients is guided by visual assessment of the contraction of the pelvic floor musculature (PFM) and/or verbal assessment of the sensation and location of sensation upon stimulation. Generally, lead placement is proceeded by needle probing. This study evaluates which location inside a single sacral foramen would be most ideal for the release of the permanent electrode lead, by measuring electromyographic (EMG) motor responses of the PFM upon stimulation of a peripheral nerve evaluation (PNE) needle., Materials and Methods: In eight patients, four standard PNE needles, and in one patient, two PNE needles, were introduced into the same foramen, parallel to the midline and parallel to each other. Position was verified by X-ray. Needles were stimulated (square pulsed waves, 210 μsec, 14 Hz) at increasing amplitudes (1-2-3-5-7-10 mA). PFM EMG was measured using the Multiple Array Probe (MAPLe) placed intravaginally or intrarectally, with 24 derivations. For this study, the mean (normalized) EMG was taken of all electrodes and different positions within the foramen were compared using the Wilcoxon signed rank test., Results: A total of 202 PFM EMG measurements were recorded upon stimulation. EMG motor responses of the PFM for current stimulation = <2 mA showed statistically significant higher mean (normalized) EMG values for needles positioned cranial, medial, and cranial-medial, in comparison to needles positioned caudal, lateral, and caudal-lateral (p = 0.004; p = 0.021; p = 0.002)., Conclusions: Our data suggest stronger PFM contractions are elicit in cranial- and medial-placed PNE needles upon stimulation with clinically relevant current amplitudes (≤ 2 mA). Placement of the lead should aim for this spot in the foramen., (© 2019 International Neuromodulation Society.)

Objectives: High-frequency (kHz) stimulation of preganglionic pelvic nerve afferents can inhibit voiding in both anesthetized and conscious rats. The afferents travel via the S1 sacral nerve root, which is easier to access than the distal pelvic nerve fibers within the abdominal cavity. We therefore investigated whether voiding could be inhibited by high-frequency stimulation at S1 and how this compared to distal pelvic nerve stimulation., Methods: Urethane-anesthetized rats were instrumented to record bladder pressure and abdominal wall electromyogram and to stimulate the distal preganglionic pelvic nerve bundle and S1 sacral root. Saline was infused continuously into the bladder to evoke repeated voiding. Stimulation was initiated within 1-2 sec of the onset of the steep rise in bladder pressure signaling an imminent void., Results: In six rats, stimulation of the distal pelvic nerve bundle (1-3 kHz sinusoidal waveform 1 mA, 60 sec) supressed the occurrence of an imminent void. Voiding resumed within 70 ± 13.0 sec (mean ± SEM) of stopping stimulation. Stimulation (using the same parameters) of the S1 root at the level of the sacral foramen suppressed voiding for the entire stimulation period in three rats and deferred voiding for 35-56 sec (mean 44.0 ± 3.2 sec) in the remaining three. Stimulation at either site when the bladder was approximately half full, as estimated from previous intervoid intervals, had no effect on voiding., Conclusions: This preliminary study provides proof-of-concept for the sacral root as an accessible target for high-frequency stimulation that may be developed as an "on demand" neuromodulation paradigm to suppress unwanted urinary voids., Conflict of Interest: The authors reported no conflict of interest., (© 2019 International Neuromodulation Society.)