Sacral neuromodulation for neurogenic lower urinary tract dysfunction: systematic review and meta-analysis

Context

Treatment of neurogenic lower urinary tract dysfunction (LUTD) is a challenge, because conventional therapies often fail. Sacral neuromodulation (SNM) has become a well-established therapy for refractory non-neurogenic LUTD, but its value in patients with a neurologic cause is unclear.

Objective

To assess the efficacy and safety of SNM for neurogenic LUTD.

Evidence acquisition

Studies were identified by electronic search of PubMed, EMBASE, and ScienceDirect (on 15 April 2010) and hand search of reference lists and review articles. SNM articles were included if they reported on efficacy and/or safety of tested and/or permanently implanted patients suffering from neurogenic LUTD. Two reviewers independently selected studies and extracted data. Study estimates were pooled using Bayesian random-effects meta-analysis.

Evidence synthesis

Of the 26 independent studies (357 patients) included, the evidence level ranged from 2b to 4 according to the Oxford Centre for Evidence-Based Medicine. Half (n = 13) of the included studies reported data on both test phase and permanent SNM; the remaining studies were confined to test phase (n = 4) or permanent SNM (n = 9). The pooled success rate was 68% for the test phase (95% credibility interval [CrI], 50–87) and 92% (95% CrI, 81–98%) for permanent SNM, with a mean follow-up of 26 mo. The pooled adverse event rate was 0% (95% CrI, 0–2%) for the test phase and 24% (95% CrI, 6–48%) for permanent SNM.

Conclusions

There is evidence indicating that SNM may be effective and safe for the treatment of patients with neurogenic LUTD. However, the number of investigated patients is low with high between-study heterogeneity, and there is a lack of randomised, controlled trials. Thus, well-designed, adequately powered studies are urgently needed before more widespread use of SNM for neurogenic LUTD can be recommended.     

Nonpharmacological treatment of lower urinary tract dysfunction using biofeedback and transcutaneous electrical stimulation: a pilot study

OBJECTIVE

To report a series of children with lower urinary tract dysfunction (LUTD) whose urge syndrome was treated by electrical stimulation, and their voiding dysfunction by biofeedback; none of the children were using anticholinergic drugs during treatment.

PATIENTS AND METHODS

In all, 36 children who presented with symptoms of urinary urgency and/or daily incontinence completed the treatment and were prospectively evaluated. The mean (range) follow‐up was 13.8 (4–24) months, and their mean age 7 (3–14) years, 17 children were aged <5 years. The children were divided into two groups: group 1, with urge syndrome treated with superficial parasacral electrical stimulation, and group 2, with voiding dysfunction, treated with biofeedback.

RESULTS

In group 1, the mean (range) number of electrical stimulation sessions was 13.1 (4–20). Of the 19 children treated, 12 had a complete clinical improvement, six a significant improvement, and one a mild improvement. In group 2, the mean (range) number of biofeedback sessions was 6 (4–14). Of the 17 children treated, there was complete improvement of symptoms in 10, significant improvement in two and mild improvement in five. Six children who had no resolution of symptoms after biofeedback had salvage therapy with electrical stimulation, after which four had complete improvement of symptoms, and two a 90% and 40% improvement, respectively. Taking the two groups together, after treatment, four children developed isolated episodes of urinary tract infection. Of 21 children with nocturnal enuresis, bed‐wetting continued in 13 (62%) after treatment.

CONCLUSION

In this short‐term follow‐up, the nonpharmacological treatment of voiding dysfunction using biofeedback, and of urge syndrome by electrical stimulation, was effective for treating LUTD in children.

     

Posterior tibial nerve stimulation as neuromodulative treatment of lower urinary tract dysfunction

PURPOSE: Recently, intermittent percutaneous posterior tibial nerve stimulation was introduced as a treatment modality filling the gap between conservative and surgical therapies in patients with certain types of lower urinary tract dysfunction. MATERIALS AND METHODS: In a prospective multicenter trial posterior tibial nerve stimulation was evaluated in 37 patients who presented with symptoms of bladder overactivity, that is the urgency and frequency syndrome and/or urge incontinence, and 12 with nonobstructive urinary retention. Results were recorded in voiding diaries and on quality of life questionnaires before and after treatment. Patients were classified as responders, including those in whom therapy was successful and chose to continue treatment after the initial 12 weeks, and nonresponders, those who chose to stop treatment. RESULTS: Overall, a positive response was seen in 60% of all patients. In patients with bladder overactivity a statistically significant decrease was observed in leakage episodes, number of pads used, voiding frequency and nocturia, and an equal increase in mean and smallest volume voided. Improvements were also seen in nonobstructive urinary retention, including number of catheterizations, total and mean volume catheterized, and total and mean volume voided. Disease specific quality of life and some domains of general quality of life improved, especially of bladder overactivity. Only mild side effects were observed. CONCLUSIONS: Posterior tibial nerve stimulation is a minimally invasive and successful treatment option for patients with certain types of lower urinary tract dysfunction.     

Electrical stimulation for the treatment of lower urinary tract dysfunction after spinal cord injury

Electrical stimulation for bladder control is an alternative to traditional methods of treating neurogenic lower urinary tract dysfunction (NLUTD) resulting from spinal cord injury (SCI). In this review, we systematically discuss the neurophysiology of bladder dysfunction following SCI and the applications of electrical stimulation for bladder control following SCI, spanning from historic clinical approaches to recent pre-clinical studies that offer promising new strategies that may improve the feasibility and success of electrical stimulation therapy in patients with SCI. Electrical stimulation provides a unique opportunity to control bladder function by exploiting neural control mechanisms. Our understanding of the applications and limitations of electrical stimulation for bladder control has improved due to many pre-clinical studies performed in animals and translational clinical studies. Techniques that have emerged as possible opportunities to control bladder function include pudendal nerve stimulation and novel methods of stimulation, such as high frequency nerve block. Further development of novel applications of electrical stimulation will drive progress towards effective therapy for SCI. The optimal solution for restoration of bladder control may encompass a combination of efficient, targeted electrical stimulation, possibly at multiple locations, and pharmacological treatment to enhance symptom control.     

Sacral neuromodulation for treatment of lower urinary tract dysfunction

Despite initial reservations, sacral neuromodulation has begun to develop as a new therapeutic tool for the treatment of lower urinary tract dysfunction. It bridges the gap between conservative treatment options and highly invasive procedures, such as urinary diversion. At present, there are no clinical variables that can reliably predict the efficacy of neuromodulation in an individual patient. All patients, regardless of indication, must therefore undergo a test stimulation before they can be offered chronic sacral neuromodulation with an implanted system. Evaluations in various clinical trials have confirmed that sacral neuromodulation, based on unilateral sacral foramen electrode implantation, has statistically significant therapeutic effects compared to controls, in patients with urge syndromes and failure to empty. The patients most likely to benefit from this treatment are those with detrusor hyperactivity or detrusor hypo-activity. Those with pain syndromes are less likely to respond and to benefit from treatment. Acute and subchronic sacral neuromodulation are associated with very low rates of complications. Complications of chronic sacral neuromodulation are caused either by surgery-related morbidity or hardware problems. Conservative treatment options should be exhausted before neuromodulation is considered. This rule has two purposes: First, it postpones surgery, with its potential morbidity, for as long as possible; second, the long-term efficacy of neuromodulation is still unclear and may be limited in some patients. A fully exploited conservative therapy, in combination with subsequent sacral neuromodulation, may therefore be the optimum way to pursue therapeutic options of relatively low invasiveness.     

Neuromuscular electrical stimulation and the treatment of lower urinary tract dysfunction in multiple sclerosis--a double blind, placebo controlled, randomised clinical trial

AIMS: Lower urinary tract dysfunction affects up to 75% of the multiple sclerosis population. Results from our recent Pilot Study (McClurg et al., 2006) indicated that a combined programme of pelvic floor muscle training, electromyography biofeedback and neuromuscular electrical stimulation modalities may alleviate some of the distressing symptoms within this population. This clinical trial aimed to evaluate further the efficacy of these interventions and to establish the benefit of neuromuscular electrical stimulation above and beyond that of EMG biofeedback and pelvic floor muscle training. METHODS: 74 multiple sclerosis patients who presented with lower urinary tract dysfunction were randomly allocated to one of two groups - Group 1 received Pelvic Floor Muscle Training, Electromyography Biofeedback and Placebo Neuromuscular Electrical Stimulation (n=37), and Group 2 which received Pelvic Floor Muscle Training, Electromyography Biofeedback, and Active Neuromuscular Electrical Stimulation (n=37). Treatment was for nine weeks with outcome measures recorded at weeks 0, 9, 16 and 24. The Primary Outcome Measure was the number of leakage episodes. Within group analysis was by Paired Samples t-test. Group differences were analysed using Repeated Measures Analysis of Variance and Post-hoc tests were used to determine the significance of differences between Groups at each time point. RESULTS: The mean number of incontinence episodes were reduced in Group 2 by 85% (p=0.001) whereas in Group 1 a lesser reduction of 47% (p=0.001) was observed. However, there was a statistically superior benefit in Group 2 when compared to Group 1 (p=0.0028). This superior benefit was evident in all other outcome measures. CONCLUSIONS: The addition of Active Neuromuscular Electrical Stimulation to a programme of Pelvic Floor Muscle Training and Electromyography Biofeedback should be considered as a first-line option in alleviating some of the symptoms of lower urinary tract dysfunction associated with multiple sclerosis.     

bTUNED: transcutaneous tibial nerve stimulation for neurogenic lower urinary tract dysfunction

Objective

To present the protocol for a randomized controlled trial (RCT) evaluating the efficacy and safety of transcutaneous tibial nerve stimulation (TTNS) for refractory neurogenic lower urinary tract dysfunction (NLUTD).

Study Design and Results

bTUNED (bladder and TranscUtaneous tibial Nerve stimulation for nEurogenic lower urinary tract Dysfunction) is an international multicentre, sham-controlled, double-blind RCT investigating the efficacy and safety of TTNS. The primary outcome is success of TTNS, defined as improvements in key bladder diary variables at study end compared to baseline values. The focus of the treatment is defined by the Self-Assessment Goal Achievement (SAGA) questionnaire. Secondary outcomes are the effect of TTNS on urodynamic, neurophysiological, and bowel function outcome measures, as well as the safety of TTNS.

Conclusions

A total of 240 patients with refractory NLUTD will be included and randomized 1:1 into the verum or sham TTNS group from March 2020 until August 2026. TTNS will be performed twice a week for 30 min during 6 weeks. The patients will attend baseline assessments, 12 treatment visits and follow-up assessments at the study end.     

Botulinum A toxin urethral injection for the treatment of lower urinary tract dysfunction

PURPOSE: This study investigates the effectiveness of botulinum A toxin in the treatment of various types of lower urinary tract dysfunction and determines the predictive factors for a successful outcome. MATERIALS AND METHODS: A total of 103 patients with chronic urinary retention (45) or severely difficult urination (58) received urethral injection of botulinum A toxin. The dose was 50 units in 48 patients and 100 units in 55. Clinical effects and urodynamic parameters were compared at baseline and after treatment. RESULTS: The 48 men and 55 women (age range 14 to 86 years) had various types of lower urinary tract dysfunction including detrusor sphincter dyssynergia in 29, dysfunctional voiding in 20, nonrelaxing urethral sphincter in 19, cauda equina lesion in 8, peripheral neuropathy in 14 and idiopathic detrusor underactivity in 13. A total of 40 (39%) patients had an excellent result and 47 (46%) had significant improvement as assessed by the patients. The total success rate was 84.5%. Among these patients mean maximum voiding pressure decreased significantly (62 +/- 40 vs 43 +/- 31 cm H2O, p = 0.000), as did maximal urethral closure pressure (65 +/- 36 vs 48 +/- 31 cm H2O, p = 0.000) and post-void residual (226 +/- 165 vs 89 +/- 112 ml, p = 0.000) at 2 to 4 weeks after treatment. Among 45 patients with urinary retention the indwelling catheters were removed or clean intermittent catheterization was discontinued in 39 (87%). CONCLUSIONS: Botulinum A toxin urethral injections at doses of 50 or 100 units were effective in decreasing urethral sphincter resistance in patients with various types of lower urinary tract dysfunction.     

影像尿动力检查在下尿路排尿障碍疾病诊断中的作用

目的 探讨影像尿动力检查在下尿路排尿障碍疾病中的应用价值.方法 2008年12月至2010年3月对115例下尿路排尿障碍患者行影像尿动力检查,确定排尿障碍类型,分析各类疾病的影像尿动力特点.结果 神经原性膀胱患者37例,男性25例,女性12例.其中逼尿肌无反射(DA)18例,膀胱过度活动(OAB)2例,低顺应性膀胱伴肾积水10例,逼尿肌-外括约肌协同失调7例.非神经原性排尿障碍患者59例,男性34例,女性25例;其中膀胱出口梗阻40例,DA 15例,单纯OAB 4例.膀胱扩大术后复查患者7例,男性4例,女性3例.可控回肠膀胱术后男性患者1例.输尿管再植术后男性患者1例.影像尿动力检查显示膀胱尿道功能基本正常者10例,男性6例,女性4例.结论 影像尿动力检查通过压力-流率曲线与实时影像结合分析,可为各类下尿路排尿障碍疾病提供准确的诊断及治疗依据.     

Sacral neuromodulation for lower urinary tract dysfunction

Objectives

To review the technique, indications, results and working mechanisms of sacral neuromodulation (SNM) for lower urinary tract dysfunction.

Methods

The available literature on SNM for lower urinary tract dysfunction was searched. Based on the information available in the literature and also based on personal experience, the urological indications, technique, mechanisms of action and results of SNM are presented and discussed.

Results

SNM for lower urinary tract dysfunction involves stimulation of the 3rd sacral nerve with an electrode implanted in the sacral foramen and connected to a pulse generator. The technique is accepted by the FDA since 1997. Currently, SNM for lower urinary tract dysfunction has been successfully used in about 26,000 patients with various forms of lower urinary tract dysfunction, including urgency, frequency and urgency incontinence as well as non-obstructive urinary retention. The actual procedure of SNM consists of a minimal invasive technique and is effective in about 70% of the patients who have been implanted with a permanent system. Also, in pelvic pain, interesting results have been described. SNM modulates the micturition reflexes at different levels in the central nervous system.

Conclusions

Sacral neuromodulation is a safe and effective therapy for various forms of lower urinary tract dysfunction, including urgency, frequency and urgency incontinence as well as non-obstructive urinary retention. It should be the first choice after failure of maximal conservative therapy.     

Pathophysiology of lower urinary tract dysfunction

Lower urinary tract dysfunction can be considered in terms of two broad categories: problems caused by abnormalities of the filling and storage phase and problems related to the voiding phase. The author prefaces this discussion with a review of normal anatomy and physiology.     

Prazosin treatment of neurological patients with lower urinary tract dysfunction

Prazosin has a selective alpha-1-adrenoceptor blocking effect and, as a result, reduces maximal urethral pressure. It decreases detrusor contractility and excitability in patients with detrusor hyperreflexia. The clinical effect of prazosin even in a high-dose regimen is only slight, but clinical investigations are at the moment few. Prazosin is well tolerated, with dizziness as the most commonly reported side effect. With this background, further studies should be performed to document a possible clinical effect in subgroups.     

Peripheral afferent nerve stimulation for treatment of lower urinary tract irritative symptoms

OBJECTIVES: To assess the efficacy of posterior tibial nerve stimulation for treatment of lower urinary tract irritative symptoms (urgency, frequency, urge incontinence and pelvic pain). PATIENTS AND METHODS: 51 female patients with a mean age of 55 years were enrolled in the study. The patients presented with the following symptoms: Frequency/urgency 26 patients (50.98%), urge incontinence 22 (43.13%) and interstitial cystitis 3 patients (5.88%).The technique consists in administering low voltage electric stimulation via a 3-5cm needle placed above the tibial malleolus. Patients received weekly stimulations of 30 minutes for a 10-week period. Quality of life questionnaires and voiding diaries before and after treatment were completed. Moreover, the results were evaluated by patients. The variables analysed include: daytime and nighttime voiding frequency, daytime and nighttime voiding volume, daytime and nighttime leakage episodes and hypogastric pain. RESULTS: A statistically significant improvement was seen in all variables, especially remarkable in relation to frequency/urgency, impact on women quality of life and hypogastric pain, being less marked in relation to leakage episodes and voiding volume. CONCLUSIONS: Afferent nerve stimulation offers an alternative treatment for managing lower urinary tract irritative symptoms. However, it would be advisable to confirm the results obtained by means of long-term randomized, follow-up studies.