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Neuromodulation for Neurogenic Lower Urinary Tract Dysfunction: Reviewing the Latest Evidence
By: Marcio A. Averbeck, MD, MSc, PhD, TiSBU | Posted on: 04 Jan 2023
Sacral neuromodulation (SNM) is an established third-line treatment for idiopathic lower urinary tract dysfunction in patients who failed conservative therapies, such as behavioral and pharmacological strategies.1 Most studies on SNM have focused on the role of this minimally invasive treatment in patients presenting with idiopathic overactive bladder (OAB), chronic nonobstructive urinary retention, and chronic pelvic pain. However, there is increasing evidence supporting the use of SNM for patients with adult neurogenic lower urinary tract dysfunction (NLUTD). According to the International Continence Society, neurogenic OAB is characterized by “urgency, with or without urgency urinary incontinence, usually with increased daytime frequency and nocturia in the setting of a clinically relevant neurological disorder with at least partially preserved sensation.”2 Neurogenic OAB is a common presentation of several neurological diseases, including central nervous system lesions (stroke, Parkinson’s disease, tumors, etc) and spinal cord lesions. Studies on SNM for patients with neurological diseases tend to follow the same criteria used for patients with idiopathic lower urinary tract dysfunction.3 This article critically discusses 2 recently published studies, which focused on the role of SNM in neurourological patients.
van Ophoven et al have performed a systematic literature review and meta-analysis of studies reporting the safety and effectiveness of SNM in patients with NLUTD (neurogenic detrusor overactivity, nonobstructive urinary retention, or a combination of both).4 Forty-seven studies were included in the systematic literature review. Twenty-one studies comprised of a total of 887 patients were included in the meta-analysis of test SNM. The pooled success rate of SNM test stimulation was 66.2% (95% CI 56.9-74.4). Depending on neurogenic conditions test success rates varied greatly. Twenty-four studies with a total of 428 patients were included in the meta-analysis of permanent SNM. The success rate of pooled permanent SNM was 84.2% (95% CI 77.8-89.0). Among the identified studies, the most common adverse events were loss of effectiveness, infection, pain at the implant site, and lead migration, with adverse event rates of 4.7%, 3.6%, 3.2%, and 3.2%, respectively. These outcomes are consistent with the meta-analysis published by Kessler et al in 2010,5 which demonstrated a pooled success rate of 68% for the test phase and 92% for permanent SNM implant, with a mean follow-up of 26 months.
More recently, Liechti et al published a sham-controlled, double-blind, multicenter trial, which included patients with refractory NLUTD at four Swiss referral centers.6 Patients underwent SNM test phase with lead placement into the sacral foramina S3 (rarely S4). A neurostimulator was implanted for permanent stimulation only in patients presenting with ≥50% improvement in key bladder diary variables (successful test phase). For 2 months, neuromodulation was optimized using subsensory stimulation with individually adjusted parameters. Thereafter, the neurostimulator remained on (SNM ON) or was switched off (SNM OFF; 1:1 random allocation to group SNM ON or SNM OFF) for 2 months, followed by a neurourological reevaluation. Of 124 patients undergoing SNM test phase, 65 (52%) were classified as therapy responders. Of these, 60 patients were randomly assigned to the intervention. After 2 months of intervention, the SNM ON group demonstrated a success rate of 76%. In the SNM OFF group, 42% of patients showed sustained SNM effects despite their neurostimulator being switched off during the last 2 months (odds ratio, 4.35; 95% confidence interval, 1.43 to 13.21; P = .009). This may be seen as the first well-designed randomized controlled trial demonstrating that SNM effectively corrected refractory NLUTD in the short term in well-selected neurourological patients. Subsensory stimulation allowed switching off the implantable neurostimulator in the control group without jeopardizing blinding. Additionally, this study did not detect notable carryover effects (>2 months), therefore supporting a need for continuous stimulation in neurourological patients. The heterogeneity of the neurological patient population, which precluded a disease-specific analysis, was the main limitation of this trial.
Although SNM is a promising treatment for neurourological patients, most studies on SNM for NLUTD are based on small sample sizes and heterogeneous populations, which are incompletely characterized in terms of severity of neurological impairment, lacking standardized definitions of success and follow-up.3 On the other hand, the need for serial imaging of the central nervous system in selected neurourological patients has represented a major barrier to the dissemination of SNM. The latest technological developments, such as rechargeable and full-body MRI-compatible devices, may help increase the level of evidence in the near future.
- Rios LA, Averbeck MA, Franca W, Sacomani CA, Almeida FG, Gomes CM. Initial experience with sacral neuromodulation for the treatment of lower urinary tract dysfunction in Brazil. Int Braz J Urol. 2016;42(2):312-320.
- Gajewski JB, Schurch B, Hamid R, et al. An International Continence Society (ICS) report on the terminology for adult neurogenic lower urinary tract dysfunction (ANLUTD). Neurourol Urodyn. 2018;37(3):1152-1161.
- Averbeck MA, Moreno-Palacios J, Aparicio A. Is there a role for sacral neuromodulation in patients with neurogenic lower urinary tract dysfunction? Int Braz J Urol. 2020;46(6):891-901.
- van Ophoven A, Engelberg S, Lilley H, Sievert KD. Systematic literature review and meta-analysis of sacral neuromodulation (SNM) in patients with neurogenic lower urinary tract dysfunction (nLUTD): over 20 years’ experience and future directions. Adv Ther. 2021;38(4):1987-2006.
- Kessler TM, La Framboise D, Trelle S, et al. Sacral neuromodulation for neurogenic lower urinary tract dysfunction: systematic review and meta-analysis. Eur Urol. 2010;58(6):865-874.
- Liechti MD, van der Lely S, Knüpfer SC, et al. Sacral neuromodulation for neurogenic lower urinary tract dysfunction. NEJM Evid. 2022;1(11):https://doi.org/10.1056/EVIDoa2200071.
Feature image photo courtesy of Duke University
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