Sacral Neuromodulation for Lower Urinary Tract and Bowel Dysfunction in Animal Models: A Systematic Review With Focus on Stimulation Parameter Selection

ObjectiveConventional sacral neuromodulation (SNM) has shown to be an effective treatment for lower urinary tract and bowel dysfunction, but improvements of clinical outcome are still feasible. Currently, in preclinical research, new stimulation parameters are being investigated to achieve better and longer effects. This systematic review summarizes the status of SNM stimulation parameters and its effect on urinary tract and bowel dysfunction in preclinical research.Materials and MethodsThe literature search was conducted using three databases: Ovid (Medline, Embase) and PubMed. Articles were included if they reported on stimulation parameters in animal studies for lower urinary tract or bowel dysfunction as a primary outcome. Methodological quality assessment was performed using the SYRCLE Risk of Bias (RoB) tool for animal studies.ResultsTwenty-two articles were eligible for this systematic review and various aspects of stimulation parameters were included: frequency, intensity, pulse width, stimulation signal, timing of stimulation, and unilateral vs. bilateral stimulation. In general, all experimental studies reported an acute effect of SNM on urinary tract or bowel dysfunction, whereas at the same time, various stimulation settings were used.ConclusionsThe results of this systematic review indicate that SNM has a positive therapeutic effect on lower urinary tract and bowel dysfunction. Using low-frequency-SNM, high-frequency-SNM, bilateral SNM, and higher pulse widths showed beneficial effects on storage and evacuation dysfunction in animal studies. An increased variability of stimulation parameters may serve as a basis for future improvement of the effect of SNM in patients suffering from urinary tract or bowel dysfunction.     

Sacral Neuromodulation in Patients With Neurogenic Lower Urinary Tract Dysfunction: A Multicenter Retrospective Study From China

ObjectivesThis retrospective study aimed to determine the effectiveness of sacral neuromodulation (SNM) on neurogenic lower urinary tract dysfunction (NLUTD) and analyze the predictive factors.Materials and MethodsFrom January 2012 to January 2020, 152 subjects with NLUTD from four medical centers in China received SNM test stimulation. Subjects were assessed via bladder diaries, postvoid residual volumes (PRVs) and neurogenic bowel dysfunction (NBD) scores before and during the testing period. Patients who showed a minimum 50% improvement in symptoms through the SNM test phase were eligible for permanent SNM implantation.ResultsThe pooled success rate for chronic urinary retention was 31.0% (40/129), which was significantly lower (p < 0.05) than the rates for frequency-urgency (64.8%, 59/91), urinary incontinence (65.2%, 30/46), and NBD score (61.7%, 82/133). The results of the risk factor analysis showed that the urinary storage symptom was a statistically significant positive predictor (p = 0.001).ConclusionsIn conclusion, SNM is an effective and reliable method for treating NLUTD, especially in patients with urinary storage symptoms. Although not all of the symptoms in every patient can be resolve, SNM still might be a superior choice together with other treatment procedures.     

Lower Urinary Tract and Bowel Disorders and Multiple Sclerosis: Role of Sacral Neuromodulation: A Preliminary Report

Objective. In the present study we wanted to determine whether sacral neuromodulation benefits patients with bladder and bowel symptoms caused by multiple sclerosis (MS). Methods. At our Institute, five patients with MS underwent unilateral implantation of a sacral neuromodulation system, InterStim (Medtronic Inc., Minneapolis, Minnesota, USA), between April 2001 and June 2002; the mean follow‐up was 30.4 months (range 24–38). The following parameters were evaluated before and after implant of the neurostimulator device: number of daily voidings, number of incontinent episodes, residual urine, Wexner score, quality of life (QoL), and psychological impact. Results. There was an overall 81.4% decrease of urgency and frequency with a significant decrease in the number of upper urinary tract infections and fever; there was a slight improvement in bowel function; there was an overall 51.8% improvement in the QoL and a discernible improvement emotional well‐being. Conclusions. Unilateral chronic sacral neuromodulation can be a valuable treatment for neurogenic bladder and bowel disorders associated with MS.     

Principles of Sacral Nerve Stimulation (SNS) for the Treatment of Bladder and Urethral Sphincter Dysfunctions

Objectives. Sacral nerve stimulation (SNS) (Medtronic, Inc., Minneapolis, MN) is an exciting new treatment for refractory voiding disorders including urinary incontinence, retention, and voiding dysfunction. It is known that both voiding and continence reflex mechanisms are organized in the sacral spinal cord and that pathologic conditions can alter the balance between these two opposing mechanisms. Methods. The background and surgical technique of SNS will be presented. This will be followed by a discussion of hypotheses on how SNS works. Results. The beneficial effects of SNS are most reasonably attributed to activation of somatic afferent axons in the sacral spinal roots. This evoked afferent activity in turn modulates sensory processing and micturition reflex pathways in the spinal cord. Hyperactive voiding can be suppressed by direct inhibition of bladder preganglionic neurons as well as inhibition of interneuroneal transmission in the afferent limb of the micturition reflex. On the other hand, voiding in patients with urinary retention can be facilitated by inhibition of reflex pathways to the urethral outlet (guarding reflexes). Conclusions. SNS, a nonablative, minimally invasive technique for urologists, holds great promise for a large number of patients who suffer debilitating and refractory urinary symptoms.     

Effect and Relationship of Gait on Subcortical Local Field Potentials in Parkinson's Disease: A Systematic Review

ObjectivesDevelopments in deep brain stimulation (DBS) technology have enabled the ability to detect local field potentials (LFPs) in Parkinson disease (PD). Gait dysfunction is one of the most prevalent deficits seen in PD. However, no consensus has been reached on the effect of gait on LFPs and the relationship between LFPs and clinical measures of gait. The objective of this systematic review was to synthesize existing research regarding the relationship between gait dysfunction and LFPs in PD.MethodsA systematic search of the literature yielded a total of ten articles, including 132 patients with PD, which met the criteria for inclusion.ResultsBeta frequency band measures showed low-to-strong correlation to clinical gait measures (r = ?0.50 to 0.82). Two studies found decreased beta power during gait; one found increased beta frequency peaks during gait; and one found higher beta power during dual-task gait than during single-task gait. One of the three studies comparing patients with and without freezing found significantly increased beta burst duration and power during gait in freezers compared with nonfreezers. All studies showed moderate-to-high methodologic quality.ConclusionsThis review highlights the need to consider the effect of gait on LFP recordings, particularly when used to guide DBS programming. Although sample sizes were small, it appears LFPs are associated to and modulated by gait in patients with PD. This evidence suggests that LFPs have the potential to be used as a biomarker of gait dysfunction in PD.     

Efficacy and Effectiveness of Percutaneous Tibial Nerve Stimulation in the Treatment of Pelvic Organ Disorders: A Systematic Review

Objective: This systematic review aimed to determine the efficacy and effectiveness of percutaneous tibial nerve stimulation (PTNS) on symptoms of overactive bladder (OAB) and pelvic organ disorders, pain, adverse events (AEs), and quality of life (QoL). Methods: A literature search was performed in September 2011 in the databases MEDLINE, CINAHL, and EMBASE. Hand searching of references was conducted. Only randomized controlled trials (RCTs) and controlled clinical trials (CCTs) with adult patients were included. Results: Seven studies met the eligibility criteria. Five RCTs indicated improvement (range 36.7–80%) on OAB symptoms, frequency, urgency, nocturia, and incontinence. One CCT reported improvement (mean 15.7) in 53% of the subjects on fecal incontinence (FI) symptoms on an FI Questionnaire (range 0–20). One RCT showed more than 50% improvement on pain (40%) and symptom scores (66.6%) in chronic pelvic pain (CPP). Limitations are the small amount, overall low quality, and variety in outcome measures of included studies. Only minor AEs were reported. No meta‐analysis was performed as a consequence of heterogeneous data. Conclusions: This systematic review provides evidence for the efficacy of PTNS on symptoms, pain, and QoL measures of OAB, FI and category IIIB CP/CPP. Evidence of effectiveness was found on symptoms and QoL for OAB. The total amount of seven included studies, from which even the most favorable study has some potential bias, is too small to draw firm conclusions. Independent high quality RCTs are necessary to confirm and delineate the range of therapeutic effects of PTNS in this region. PTNS is a safe intervention.     

Implant‐Driven Tibial Nerve Stimulation in the Treatment of Refractory Overactive Bladder Syndrome: 12‐Month Follow‐up

Objectives. To investigate feasibility and safety of implant‐driven tibial nerve stimulation. Materials and Methods. Eight patients with refractory overactive bladder were successfully treated with implanted percutaneous tibial nerve stimulation (PTNS). Patients were evaluated with bladder diaries, quality of life questionnaires, and physical examination before implantation, and at 3, 6, and 12 months of follow‐up. The primary objective was ≥ 50% reduction of the number of incontinence episodes and/or voids on bladder diary. The Wilcoxon signed ranks test was used. Results. At 3, 6 and 12 months, respectively five, six, and four patients met the primary objective. At 3‐ and 6‐month follow‐up, voiding and quality of life parameters had significantly (p < 0.05) improved. Urinary tract infection, temporarily walking difficulties, and spontaneous radiating sensations were reported as adverse events and no local infection, erosion, or dislocation. Conclusions. Implant‐driven tibial nerve stimulation seems to be feasible and safe.     

Staphylococcus Aureus Swabbing and Decolonization Before Neuromodulation Procedures: A Systematic Review and Meta-Analysis

IntroductionStaphylococcus aureus (S aureus) is the foremost bacterial cause of surgical-site infection (SSI) and is a common source of neuromodulation SSI. Endogenous colonization is an independent risk factor for SSI; however, this risk has been shown to diminish with screening and decolonization.Materials and MethodsA systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using the PubMed, Cochrane Library, and Embase data bases from inception to January 1, 2022, for the purposes of identifying all studies reporting on the use of S aureus swabbing and/or decolonization before neuromodulation procedures. A random-effects meta-analysis was performed using the metaphor package in R to calculate odds ratios (OR).ResultsFive observational cohort studies were included after applying the inclusion and exclusion criteria. The average study duration was 6.6 ± 3.8 years. Three studies included nasal screening as a prerequisite for subsequent decolonization. Type of neuromodulation included spinal cord stimulation in two studies, deep brain stimulation in two studies, intrathecal baclofen in one study, and sacral neuromodulation in one study. Overall, 860 and 1054 patients were included in a control or intervention (ie, screening and/or decolonization) group, respectively. A combination of nasal mupirocin ointment and a body wash, most commonly chlorhexidine gluconate soap, was used to decolonize throughout. Overall infection rates were observed at 59 of 860 (6.86%) and ten of 1054 (0.95%) in the control and intervention groups, respectively. Four studies reported a significant difference. The OR for intervention (screen and/or decolonization) vs no intervention was 0.19 (95% CI, 0.09–0.37; p < 0.001). Heterogeneity between studies was nonsignificant (I² = 0.43%, τ² = 0.00).ConclusionsPreoperative S aureus swabbing and decolonization resulted in significantly decreased odds of infection in neuromodulation procedures. This measure may represent a worthwhile tool to reduce neuromodulation SSI, warranting further investigation.     

Neuromodulation of the Pudendal,Hypogastric, and Tibial Nerves With Pelvic Floor Muscle Rehabilitation in the Treatment of Urinary Urge Incontinence

ObjectivesThe hypothesis of the study is that adding percutaneous tibial nerve neuromodulation (Urgent PC, Uroplasty Inc., Minneapolis, MN, USA) with pelvic floor muscle rehabilitation (Evadri System, Hollister Inc., Libertyville, IL, USA) is safe, and more successful than either therapy alone for the treatment of urge incontinence.Material and MethodsTwo hundred and fifty-six female patients with urge incontinence or mixed incontinence were included in this investigation. Patients were treated sequentially (on the same day) with both pelvic floor muscle rehabilitation and percutaneous tibial nerve neuromodulation twice per week at the Southern Arizona Urogynecology Center, Tucson, Arizona.ResultsAt three months 93% of the patients were dry. The remaining 7% of patients had a mean improvement of 84% in their incontinence episodes. The median follow-up is now 19 months. There were no adverse side events.ConclusionsNeuromodulation of the pudendal, hypogastric, and tibial nerves is a highly effective treatment for urge incontinence, and superior to either treatment alone by a factor of greater than two times (see Table 1).     

Utility of Electrical Neuromodulation for Treating Chronic Pain Syndromes in the Pediatric Setting: A Systematic Review

ObjectivesChronic pain syndromes in children can carry significant threats to psychological well-being, opioid overuse, functional impairments, and severe disability. While several high-level studies, almost exclusively in adults, have demonstrated the utility of implantable electrical neuromodulation systems for treating various chronic pain syndromes, there exists a paucity of pediatric-specific evidence. Unfortunately, evidence and practice patterns established from adults may not be fully translatable to children given differences in disease manifestations and anatomical variances.Materials and MethodsWe performed a systematic review using conventional PRISMA methodology to identify studies reporting use of implantable electrical neuromodulation systems in children. The primary outcome parameters collected were analgesic relief and functional benefits. Additionally, previous interventions attempted, neuromodulation parameters, and limitations were collected as reported.ResultsA total of 11 studies was identified, which described 19 patients who were refractory to multidisciplinary pain management strategies. The cohort was mostly adolescent (18/19), suffered from CRPS (14/19), and received SCS (17/19). Nearly all patients, both those with CRPS (13/14) and non-CRPS conditions (4/4), reported significant pain relief and functional recovery following neuromodulation. There were no severe complications reported; limitations included suboptimal benefit or loss of analgesia (3/19), lead or device revision (3/19), and subcutaneous infection (1/19), all of which were congruent with adult outcomes.ConclusionThere exist children with chronic pain refractory to standard of care approaches who could be considered for neuromodulation interventions. The existing data, which was limited and from a low tier of evidence, suggest that these interventions are relatively safe and provide meaningful pain reduction and functional improvements. While not previously reported, we recommend careful consideration of the pubertal growth spurt prior to device lead placement—if reasonable and appropriate—given the possibility of inferior lead migration with physiologic growth in patients with SCS devices or foraminal extrusion in patients with dorsal root ganglion stimulation devices.