Efficacy and Safety of Sacral Neuromodulation on Patients With Multiple Sclerosis and Lower Urinary Tract Dysfunction: A Systematic Review and Meta‐Analysis

ABSTRACT

Aim

Treating multiple sclerosis (MS)‐related adult neurogenic lower urinary tract dysfunction (ANLUTD) is challenging because conservative treatments are often ineffective. Sacral neuromodulation (SNM) is a promising minimally invasive treatment of ANLUTD. This review assesses the efficacy and safety of SNM for MS‐related ANLUTD.

Methods

Studies were identified through electronic searches of PubMed and Scopus from inception to August 9, 2024, supplemented by backward and forward manual searches. All studies included were original articles investigating the impact of SNM on urinary symptoms in patients with MS and ANLUTD. Three independent reviewers assessed the quality of evidence using the Oxford Centre for Evidence‐Based Medicine criteria and the ROBINS‐I tool.

Results

Seventeen studies involving 192 patients with MS undergoing SNM were included. The analysis revealed overall success rates of 80% (95% CI, 76%–91%) and 74% (95% CI, 62%–86%) for the test phase (stage I) and permanent SNM (stage II), respectively. Subgroup analyses explored limitations and potential sources of heterogeneity, including gender and type of urinary dysfunction, offering deeper insight into the effectiveness of SNM. With respect to safety, the pooled incidence of complications was approximately 7%, the majority of which were minor and manageable.

Conclusions

This systematic review highlights the potential of SNM to improve urinary symptoms in patients with MS‐related ANLUTD, although the quality of evidence remains low. Further adequately powered randomized clinical trials are needed to clarify long‐term efficacy and safety.

1. Introduction

Multiple sclerosis (MS) is a condition that affects the central nervous system. It is characterized by immune‐mediated inflammatory demyelinating lesions that cause a wide range of symptoms, including problems with vision, movement, sensation, balance, and bladder function [1]. MS is the most common neurological disease in people aged 20–40, and 50%–90% of patients with MS experience lower urinary tract symptoms (LUTS) [2]. These patients may develop storage symptoms, such as urinary urgency (40%–99%), urgency incontinence (30%–66%) [3], and voiding dysfunction (25%–45%) [4]. Symptom severity depends on the type and extent of nervous system damage caused by MS. The progression of lower urinary tract dysfunction is typically proportional to MS evolution [5].

Historically, anticholinergics were the primary drugs used to treat neurogenic overactive bladder in patients with MS [3]. However, anticholinergic tolerability can increase the risk of urinary retention and cognitive impairment. A Cochrane review revealed that 20% of patients with MS receiving anticholinergic drugs in clinical trials discontinued treatment because of adverse effects [6]. β3 agonists (e.g., mirabegron), which carry a lower risk of urinary retention and have higher persistence rates than anticholinergics, are an option for patients with neurogenic LUTS who are refractory to antimuscarinic drugs or cannot tolerate their adverse effects [7]. However, despite reported improvement in neurogenic LUTS, mirabegron has not shown significant effects on detrusor pressure or cystometric capacity in patients with MS [8]. Intravesical botulinum toxin injection, a third‐line treatment, is also a key therapy for LUTS in patients with MS, as it improves bladder capacity, urinary frequency, urgency, and incontinence. However, it may decrease bladder voiding efficiency and increase the risk of urinary retention [9]. These adverse effects are particularly problematic for patients with restricted manual dexterity or mobility, particularly in women with MS, who may struggle to perform clean intermittent catheterization [9].

Over the past three decades, sacral neuromodulation (SNM) has become an established treatment for conditions such as refractory non‐obstructive chronic urinary retention and refractory overactive bladder syndrome, following standardization of the surgical technique since its seminal description by Matzel et al. [10, 11] Initially, SNM was considered unsuitable for ANLUTD, however, however, according to the most recent EAU guidelines, SNM is considered a minimally invasive therapeutic option for carefully selected patients with ANLUTD [12]. This review aimed to determine the efficacy of SNM in treating MS‐related ANLUTD.

2. Methods

2.1. Search Strategy

This systematic review and meta‐analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses Protocols (PRISMA‐P) guidelines [13], and the protocol was registered in the International Prospective Registry of Systematic Reviews (PROSPERO; ID:42024588697). Terminology related to adult neurogenic lower urinary tract dysfunction was applied in accordance with ICS standardization reports [14]. The primary objective was to assess the impact of SNM on patients with MS with ANLUTD. A comprehensive search strategy was formulated; the details of the population, intervention, comparison, outcome, and study design (PICOS) elements, along with the corresponding search strings, are available in the Supplementary Material (Appendix B, Supplement A). The electronic searches were supplemented by backward and forward manual searches.

An extensive literature search was systematically conducted across PubMed and Scopus (Appendix A and B) on August 9, 2024. No language or publication date filters were applied to increase the number and range of relevant studies.

2.2. Eligibility Criteria

All included studies were original research articles investigating the impact of SNM on urinary symptoms in patients with MS and neurogenic ANLUTD (Appendix B, Supplement B). In addition, studies were only included if they reported previously unpublished data, included clear outcome measures related to urinary function, and provided data on the clinical symptoms, urodynamic assessment, or quality of life scores before and after SNM treatment.

Duplicate records were eliminated before the screening process through an automated de‐duplication mechanism, facilitated by the screening platform Rayyan (Rayyan Systems, Inc.). Three independent reviewers (P.S., Z.A., and S.F.) conducted the initial title and abstract screening, followed by a full‐text review of potentially eligible studies. Any discrepancies between reviewers were resolved through internal discussion.

2.3. Data Extraction and Quality Assessment

The data extraction process involved thorough documentation of pertinent details, including study characteristics, participant demographics, intervention specifics, and outcomes (Appendix B, Supplement C).

The quality assessment of included studies was based on level 4 evidence, following the Oxford Centre for Evidence‐Based Medicine′s criteria for classifying evidence levels and study types [15]. Additionally, the methodological quality of the nonrandomized studies was evaluated using the ROBINS‐I tool (Table 2) [16].

Table 2.

Risk of bias assessment of included articles.

Authors	Year	Due to confounding	Selection of participants	Classification of interventions	Due to deviations from intended interventions	Due to missing data	Measurement of outcomes	Selection of the reported result
Bosch et al. [21]	1996
Hohenfellner et al. [25]	1998
Chartier‐Kastler et al. [18]	2000
Wallace et al. [26]	2007
Van Rey et al. [30]	2009
Marinkovic et al. [28]	2010
Chaabane et al. [29]	2011
Denzinger et al. [16]	2012
Minardi et al. [23]	2012
Otto et al. [20]	2012
Andretta et al. [22]	2014
Engeler et al. [24]	2015
Al‐Azzawi et al. [17]	2018
Banakhar et al. [19]	2022
Chen et al. [31]	2022
Liechti et al. [32]	2022
Thys et al. [27]	2023
Critical		Serious		Moderate	Low		No information

Note: Color coding represents the level of risk of bias: red = critical; orange = serious; yellow = moderate; green = low; blue = no information.

2.4. Data Synthesis and Analysis

Statistical heterogeneity was assessed using the I² statistic, and a DerSimonian–Laird random‐effects meta‐analysis was conducted when feasible to ensure methodological rigor. Publication bias was assessed using funnel plots and the Egger test (Appendix B, Supplement E). All analyses were performed using R 4.2.0 (R Foundation for Statistical Computing, Vienna, Austria). Statistical significance was set at p < 0.05.

3. Results

The electronic database search yielded 173 records, and an additional seven were identified through manual searches (Figure 1). After de‐duplication, the total number of records was reduced to 169, 152 of which did not meet the eligibility criteria. Studies were excluded for the following reasons: involvement of nonhuman subjects (n = 7), inclusion of patients with neurological diseases other than MS (n = 26), absence of SNM treatment (n = 61), classification as replies or background articles (n = 44), lack of assessment of SNM′s effect on MS‐related NLUTS (n = 10), or patient overlap (n = 4). Thus, 17 records were eligible for comprehensive review.

Figure 1.

Flow diagram of literature searches and results. LUTD, lower urinary tract dysfunction; MS, Multiple Sclerosis; SNM, sacral neuromodulation;

3.1. Study and Patient Characteristics

The level of evidence of the 17 studies included in the meta‐analysis ranged from 1 to 4 (Appendix B, Supplement C). Five were prospective cohort studies [17, 18, 19, 20, 21], 11 were retrospective case series [22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32], and one was a prospective randomized controlled trial with a double‐blind design [33]. Eight articles analyzed only patients with MS who received SNM [22, 23, 24, 25, 28, 29, 30, 31]. The other nine were not MS‐exclusive studies (i.e., they enrolled patients with other neurological diseases) [17, 18, 19, 20, 21, 26, 27, 30, 33]. The studies included a total of 192 patients with MS; 125 patients (65%) were women, 49 (25.5%) were men, and gender was not reported for 18 (9.4%). The mean age ranged from 34 to 55.2, and the mean duration of the underlying neurological disease ranged from 9.3 to 13.6 years in studies that provided these data. Four articles reported the baseline disability status of patients with MS; most were fully ambulatory, while some required continuous assistance or used a wheelchair (Table 1) [22, 23, 25, 29]. Three articles reported the pre‐implantation subtype of MS, specifying that patients had primary or secondary MS without progression in the past 12 months [23, 25, 29]. All articles reported data on the test phase and permanent implantation phase.

Table 1.

The methodological details of the included studies.

Authors	yr of the study	Study type	No. of patients	Female/Male	Mean MS duration, years	EDSS (Range)	Mean follow‐up, mo.	Study included data on	Outcome variables	Success rate
Banakhar et al. [20]	2022	PCS	5	3/2	NR	NR	29	T + P	● Mean voided volume/24 h	66.7%
									● Mean voided frequency/24 h
								T = 60% positive response	● Mean leaking episodes/24 h
									● Overall mean PVR
								3 implanted IPG	● No. of CIC/24 h
									● Patient Satisfaction questionnaire
Chen et al. [32]	2022	RCS	15	13/2	NR	NR	4	T + P	● Questionnaires	80%
									● UDI‐6
								T = 100% response	● IIQ‐7
									● GRA
Chartier‐Kastler et al. [19]	2000	PCS	5	5/0	11.2	NR	43.6	T + P	● mean voided volume/24 h	100%
									● mean voided frequency/24 h
									● mean leaking episodes/24 h
									● Pad Use
								T = 100% positive response	● Max. bladder capacity before leakage (mL)
									● Vol. at first uninhibited contraction
									● Detrusor pressure at max. unstable contraction (
Chaabane et al. [30]	2011	RCS	13	NR	NR	NR	51.6	T + P	● Mean post void residual volume	57.1%
									● Mean maximum flow rate
									● Mean maximum cystometric capacity
								T = 53.8% positive response	● Mean compliance
									● Mean maximum urethral closure pressure
								10 IPGs
Liechti et al. [33]	2022	RCT	15	10/5	NR	NR	2	T + P	● No. of voids/d	100%
								T = 53.3% positive response	● No. leaks/d
								8 IPGs	● Mean post void residual volume
Marinkovic et al. [29]	2010	RCS	14	14/0	9.28	Mean (range) = 4.03 [2.5–7]	51.84	T + P	● Mean CIC volume	100%
								‐T = 85.7 positive respose	● Mean Postovoid residual volume
								12 IPGs
Thys et al. [28]	2023	RCS	5	4/1	NR	NR	8.83	T + P	● M‐ISI	100%
Al‐Azzawi et al. [18]	2018	PCS	1	NR	NR	NR	NS	T + P	● No. voids/d	0%
									● Vol voided/d
									● Leakage episodes/d
									● No. of CICs/d
									● Volume of CICs/d
Wallace et al. [27]	2007	RCS	16	16/0	NR	NR	12.4	T + P	● No. voids/d	61.5%
								T = 81% positive response	● nocturia episodes
									● No. leakage episodes/d
								13 IPGs	● No. of pads/d
									● No. of CICs/d
Denzinger et al. [17]	2011	PCS	3	3/0	NR	NR	NS	T + P	● No. voids/d	100%
								T = 100% positive response	● post void residual volume/d
									● No. of CICs/d
Hohenfellner et al. [26]	1998	RCS	1	1/0	NR	NR	NS	T + P	● Voiding diary	100%
								T = 100%positive response	● urodynamic parameters
Engeler et al. [25]	2015	RCS	17	13/4	8 (median)	Median (range) = 5 (3–7.5)	2	T + P	● Volume voided/d	87.5%
									● post void residual volume
								T = 94.1% positive response	● No. of voids/d
									● No. of leakage episodes/d
								16 IPGs
Minardi et al. [24]	2012	RCS	25	10/15	13.6	NR	49.4	T + P	● Volume voided/d	100%
									● post void residual volume
									● No. of voids/d
								T = 60% positive response	● No. of leakage episodes/d
									● No. of CICs/d
									● I‐QoL
								15 IPGs
Andretta et al. [23]	2014	RCS	17	13/4	13.5	Mean (SD) = 5.8 (1.8)	52	T + P	● No. of voids/d	76.5%
									● No. of leakage episodes/d
								T = 100% positive response	● Symptoms improvement (“After SNM did you detect any significant and lasting improvement in your bladder symptoms?”
									● QoL (“How much your quality of life changed?”)
Bosch et al. [22]	1996	RCS	6	6/0	12.8	Mean (range) = 5.75 (4–7.5)	6	T + P	● No. voids/d	100%
								T = 66.7% positive response	● No. leakage episodes/d
									● No. of pads/d
								4 IPGs	● Mean voided volume/micturation
									● Urodynamic parameters
Van Rey et al. [31]	2009	RCS	30	14/16	16.9	4	24	T + P	● Voiding diary parametersa	21.4%
								T = 56.6% positive response	● No. voids/d
									● No. leakage episodes/d
								17 IPGs	● MS 54 Quality of Life (QoL)
									● Urodynamic parameters
Otto et al. [21]	2012	PCS	4	NS	NS	NR	11 (median)	T + P	● No. voids/d	0%
								T = 100% positive response	● Voided volume/d
								4 IPGs	● No. leakage episodes/d
									● No. of pads

Abbreviations: CIC, clean intermittent catheterization; EDSS, Expanded Disability Status Scale; Global Response Assessment; I‐QoL, Quality of Life Specific to Urinary Incontinence; Incontinence Impact Questionnaire; M‐ISI, Michigan Incontinence Symptom Index; NR, not reported; NS, not specific to MS patients; PCS, Prospective Cohort Study; P, Permanent Sacral Neuromodulation; PVR, Post‐void Residual; RCS, Retrospective Case Series; RCT, Randomized Clinical Trial; T, test phase; UDI‐6, Urogenital Distress Inventory.

^a Voiding diary is a tool to evaluate the number of voids/day, voided volume/day, urge and/or urge‐incontinence episodes, number of leakages, number of pads, post void residual volume and number of clean intermittent catheterizations.

3.2. Efficacy

According to the literature [5], treatments with an improvement of > 50% in bladder diary variables (number of leakages, pad use, number of voids, and number of catheterizations) are considered successful. Two articles did not report bladder diary outcomes; instead, successful outcomes were defined by improvements in symptoms or quality of life [28, 32]. Table 1 summarizes the methodological details of the included studies. The outcomes reported in individual studies are summarized and compared in the Supplementary Material (Appendix B, Supplement F).

Overall, 192 patients across the 17 studies underwent SNM testing. The overall effect estimate was 0.80 (95% CI, 72%–89%), indicating an average success rate of 80% with a relatively narrow confidence interval, suggesting a precise estimate (Figure 2). An I² of 66.99% (Figure 2) indicates moderate to high heterogeneity, suggesting important differences among studies in populations, methods, or other characteristics.

Figure 2.

Efficacy of sacral neuromodulation test (stage I) in patients with MS.

Overall, 143 patients with MS across the 17 studies received permanent SNM implantation, with a mean follow‐up of 26 months. Of these patients, 90.1% (130 of 143) had only one lead implanted, and 9.9% (13 of 143) had bilateral leads. Three patients did not receive implantable pulse generators (IPGs) despite having a positive tined lead test [31].

The overall effect estimate was 0.74 (95% CI, 62%–86%), indicating an average success rate of 74% across the studies (Figure 3). We observed significant heterogeneity (I² = 82.17%), suggesting differences in methodologies, patient populations, or definitions of success across the included studies. Despite this variability, the pooled data suggest a relatively high overall success rate for permanent implantation.

Figure 3.

Efficacy of sacral neuromodulation definitive implantation (stage II) in patients with MS.

Some series did not report SNM outcomes stratified by different patterns of MS‐related ANLUTD, such as urgency, urge incontinence, or urinary retention [18, 20, 21, 23, 27, 30, 32, 33]. However, in six studies that specifically reported success rates for patients with storage symptoms, all 23 patients (100%) demonstrated an improvement of over 50% in bladder diary variables (e.g., reduced episodes of urgency or urge incontinence), symptoms, or quality of life [19, 24, 25, 26, 28, 31]. Conversely, in the three studies [17, 25, 29] reporting outcomes related to voiding dysfunction alone, 29 of 31 patients (93.5%) achieved more than a 50% improvement in bladder diary variables (e.g., number of voids, voided volumes, or number of catheterizations), symptoms, or quality of life. Additionally, three studies [19, 22, 24] reported the success rate of SNM in patients with MS with storage and voiding symptoms; all 17 patients (100%) in these studies showed improvements in clinical or bladder diary parameters. Two studies reported outcomes based on the disability status of patients with MS [23, 25]. One study found that patients with baseline Expanded Disability Status Scale (EDSS) scores below 6 (i.e., able to walk 100 m or more unaided) had significantly greater satisfaction after a 3‐year follow‐up compared with those with EDSS scores of 6 or higher (n = 8 vs. 5, respectively; p = 0.025) [25]. Finally, different subtypes of MS appeared to result in similar outcomes, including in patients with primary or secondary forms, provided there were no relapses in the past 12 months [23, 25, 29].

3.3. Safety

Fifteen articles mentioned complications or adverse events [17, 18, 19, 20, 21, 22, 24, 25, 26, 27, 28, 29, 30, 31, 32]. Nine of these specifically reported adverse events or complications in patients with MS (Supplement D) [19, 20, 22, 24, 25, 28, 29, 31, 32]. Of those, five reported no adverse effects and no need for reintervention [19, 22, 24, 28, 32]. Six articles did not specify whether these complications occurred in patients with MS or those with other neurogenic conditions [17, 18, 21, 26, 27, 30]. No complications were reported during the testing phase.

Ten patients (8.1%) underwent surgical revision during follow‐up due to problems at the electrode site [20, 25, 31]. Three patients (2.4%) underwent reoperations for battery wear during the follow‐up period [29]. Subsequent revisions involving electrode exchange or battery replacement were performed and were effective in all reported cases. One article reported that two patients (13.3%) had the IPG removed after 36 and 42 months, respectively, because of progressive disease and symptom relapse [24]. Eleven patients (11%) had a favorable initial response, but the beneficial effect was not sustained during follow‐up (Supplement D).

4. Discussion

4.1. Main Findings

This analysis of 17 studies involving 192 patients with MS who underwent permanent SNM implantation provides insight into the efficacy of this intervention. The main finding of this review is the high success rate observed across the included studies, with pooled success rates of 80% and 74% for the test and permanent phases, respectively. This indicates that SNM is a promising therapeutic option for patients with MS and ANLUTD.

Despite these encouraging findings, the overall quality of evidence in the included studies was relatively low, highlighting the need for more RCTs. Additionally, demographic characteristics and urinary symptoms in patients with MS may be predictive of success after IPG implantation; however, these factors remain unclear because of the lack of disease‐specific studies.

The overall safety profile of SNM is favorable. Data from the 15 studies documenting adverse events [17, 18, 19, 20, 21, 22, 24, 25, 26, 27, 28, 29, 30, 31, 32] suggest that although complications such as reoperation occur, they are infrequent and generally manageable, supporting the procedure′s safety.

4.2. Findings in the Context of Existing Evidence

Two systematic reviews have evaluated the use of SNM for ANLUTD, including patients with MS. Kessler et al. [34] analyzed four case series, sixteen retrospective studies, and six prospective cohort studies. The pooled success rates were 68% for the test phase and 92% for permanent SNM implants, with a mean follow‐up of 26 months; however, outcomes specific to patients with MS were not detailed [34]. Conversely, Van Ophoven et al. conducted a systematic review and reported a 76.6% success rate (95% CI, 66.7%–84.7%) for permanent SNM among patients with MS [35].

Overall, the findings of our review of patients with MS‐related ANLUTD are consistent with those of the two systematic reviews discussed above [34, 35]. Moreover, the efficacy and safety outcomes for SNM in patients with MS in our review are similar to those of patients with non‐neurogenic dysfunction [12, 36]. Adverse events occurred in 7.3% of patients with MS, and surgical revisions for lead or battery replacement were required in 10.5% of cases. These rates are notably lower than those in the recent large‐scale INSITE study, which reported a 22% rate of undesirable changes in stimulation, a 15% rate of implant site pain, and additional surgical intervention for battery replacement in 33.5% of patients [37].

Most centers now favor unilateral over bilateral implantation (≈90%), reflecting current clinical practice and supported by systematic reviews reporting comparable or superior outcomes with a single electrode [34, 35].

4.3. Implications for Research

Given the heterogeneous nature of MS‐related ANLUTD, research in patients with varying MS presentations, stages, and LUTD patterns is necessary to accurately predict the long‐term outcomes of SNM. The studies reporting gender differences [17, 19, 20, 22, 23, 24, 25, 26, 27, 28, 29, 31, 32, 33] (49 males of 174 patients) reflected the gender prevalence ratio typically observed in MS populations. However, this outcome analysis did not consider gender differences. Moreover, two series in our meta‐analysis reported no success after the permanent implantation [18, 21], and one study [31] reported a success rate of 21.4% after the test phase and permanent implant. These reports highlight the need to determine the best indication for SNM in patients with MS. For example, in the abovementioned study [31], only 17 of 30 patients showed a positive response after the test phase; after a 2‐year follow‐up, 11 patients presented a drop in SNM response due to MS progression. Conversely, Minardi et al. reported a success rate of 60% after a mean follow‐up of 61.2 months (range: 12–108 months) [24]. This suggests that patients with “stable disease” may be more suitable candidates for treatment than those with relapsing progressive MS. The appropriate relapse‐free period to propose SNM to a patient with MS is still debated.

While most studies appear to have employed tined lead testing, very few explicitly specified whether percutaneous nerve evaluation (PNE) or stage I tined lead was performed. Furthermore, no study to date has assessed whether the presence of MS should influence the choice of testing strategy. Prolonged test phases with tined leads may improve patient selection and cumulative success, but this is not specific to MS [38]. Future research should clarify these aspects, as disease progression may affect test outcomes and ultimately guide patient selection.

In the past, SNM was not used in the neurogenic population, especially in patients with MS, as the devices were incompatible with magnetic resonance imaging (MRI). Recent improvements in the devices, including MRI compatibility and the introduction of long‐lasting, rechargeable batteries, make this a valid option for neurogenic patients who do not respond to or decline conservative treatments or short‐term medical therapies such as botulinum toxin A injections [39].

In conclusion, adequately powered RCTs are needed to allow clinicians to draw definitive conclusions about SNM efficacy in patients with MS. Such prospective trials should rigorously assess neurological disease level, disability status, urodynamic parameters, validated disease‐ and condition‐specific quality‐of‐life data, and cost‐effectiveness, with outcomes reported in accordance with the Consolidated Standards of Reporting Trials (CONSORT) guidelines [40].

4.4. Implications for Practice

Growing evidence supports the use of SNM in patients with ANLUTD. Studies on SNM in patients with neurological conditions often apply the same criteria established for idiopathic ANLUTD [41]. However, the progressive nature of MS impacts ANLUTD over time, potentially altering the efficacy of SNM. For example, SNM may be effective initially in a patient with MS but could lose efficacy following MS relapses. Patients should be informed that the device may lose efficacy if the disease progresses rapidly. Several studies in our review did not report the mean follow‐up duration or provide specific follow‐up data for patients with MS, nor did they indicate whether patients experienced relapses. This lack of detailed reporting may limit the reliability of our conclusions regarding the efficacy of SNM in patients with MS.

Notably, the pooled success rate of 74% for managing ANLUTD in patients with MS—particularly after failure of conservative treatments—suggests that SNM is an effective, reversible, minimally invasive option. SNM may enable patients to avoid continence pads, more invasive or repeated surgeries, and lifelong catheterization, which is frequently associated with significant complications. Finally, one study [28] reported outcomes in patients experiencing both ANLUTD and bowel dysfunction. Given SNM′s demonstrated efficacy in treating both conditions, individuals with coexisting dysfunctions may be ideal candidates for SNM, which could improve their quality of life [28].

4.5. Limitations

Several limitations should be noted, including heterogeneity among the included studies, variations in study design, outcomes definitions and differences in SNM protocols. A major concern is the overall low methodological quality, as most studies were retrospective case series or small prospective cohorts. In addition, many included mixed neurological populations, making it difficult to isolate MS‐specific outcomes. Notably, eight of the 17 studies reported fewer than six MS patients, which further limits the robustness and generalizability of the results. Finally, earlier surgical techniques differed markedly from contemporary SNM procedures, which could account for part of the variability in reported success rates.

5. Conclusion

This systematic review highlights the growing evidence supporting the effectiveness of SNM in patients with MS experiencing ANLUTD. However, quality evidence is low and further prospective trials with rigorous study designs are needed. Establishing a central registry for patients with MS undergoing SNM would also provide valuable data to improve patient selection, clinical decision‐making, predictive factors, and outcomes for this population.

Author Contributions

Carlos Ferreira had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study Concept and design: Carlos Ferreira, Paula Soeiro, Sara Fonseca, Zaruhi Arakelyan. Acquisition Data: Carlos Ferreira, Paula Soeiro, Sara Fonseca, Zaruhi Arakelyan. Analysis and interpretation of data: Carlos Ferreira, Paula Soeiro, Sara Fonseca, Zaruhi Arakelyan. Drafting the manuscript:Carlos Ferreira. Critical revision of the manuscript for important intellectual content: Tiago Antunes Lopes, Joana Guimarães, João Silva, Carlos Silva and Francisco Cruz. Statistical analysis: Carlos Ferreira, Paula Soeiro, Sara Fonseca, Zaruhi Arakelyan. Supervision: Tiago Antunes Lopes, Joana Guimarães.

Ethics Statement

This study was approved by the Ethics Committee of Hospital de São João, Porto, Portugal (approval number: 287, date: 23.01.2025).

Consent

The authors have nothing to report.

Conflicts of Interest

The authors declare no conflicts of interest.

Supporting information

Supplement A ‐ Search terms structured using the PICO(s).

Supplement B ‐ Inclusion and Exclusion Criteria.

Supplement C ‐ Data extraction.

Supplement D. Postoperative complications specifically reported amongst MS patients in this meta‐analysis.

Supplement E ‐ Publications Bias Plot.

Supplement F ‐ Matching Outcomes from individual Studies.

supmat.

Appendix A. Search Strategy

(((Multiple Sclerosis) AND (“sacral neuromodulation” OR “sacral nerve modulation” OR “sacral nerve stimulation” OR “neuromodulation” OR “neurostimulation” OR “sacral neurostimulation” OR “S3” OR “Sacral spinal nerve stimulation,”)) AND (“neurogenic lower urinary tract symptoms” OR “neurogenic bladder” OR “overactive bladder” OR “neurogenic overactive bladder” OR “neurogenic urinary tract dysfunction” OR “bladder dysfunction” OR “neurogenic lower urinary tract dysfunction” OR “nlutd”)) NOT (Review OR Comment OR Editorial).

Appendix B. Supplementary data

Supplementary data associated with this article can be found in the online version.

Data Availability Statement

The authors have nothing to report.