Sacral Neuromodulation (SNM) and Percutaneous Tibial Nerve Stimulation (PTNS) have been used in overactive bladder (OAB) patients with multiple sclerosis (MSP) who are refractory to behavior modification and pharmacotherapy, but the data on medium to long-term efficacy and safety of neuromodulation in OAB is very sparse. In addition, most prior studies and review articles have two major flaws: 1) they combine MS with other neurologic conditions, and/or 2) they do not adhere to the ICS definition of OAB in which urinary urgency is the sine qua non for a diagnosis of OAB.
The aim of this systematic review was to assess 1) the efficacy and adverse events of neuromodulation on OAB symptoms in MSP, based on strict inclusion and outcome criteria and 2) the scientific quality of the studies included in the review.

This was an English-language systematic review of the literature on the efficacy of neuromodulation for overactive bladder in patients with multiple sclerosis. Pubmed and Scopus were searched from 2005 to 2022 using the following search terms – “multiple sclerosis or MS,” “overactive bladder or OAB or overactive urinary bladder,” “neurogenic bladder,” “urinary urgency or urge incontinence or urinary incontinence,” and “detrusor overactivity or neurogenic detrusor overactivity or detrusor instability or neurogenic detrusor instability.” The search results were narrowed down by looking for neuromodulation treatment of OAB symptoms in patients with MS.  Non-English language articles, review articles, animal studies, studies on patients with MS with no OAB symptoms, studies on OAB in patients who were not diagnosed with MS or studies that exclude MS patients, and studies on OAB in patients with spinal injury were excluded. Table 1 lists the 6 studies included in this review according to underlying disease and type of treatment.
For the purpose of this study, we evaluated efficacy in two different ways 1) based on the criteria established by the authors of each study (Authors) and 2) criteria established by the authors of this review (Reviewers) which were divided into primary and secondary outcomes. Primary outcomes included metrics that assess the severity of the essential symptoms of OAB – urinary urgency, urge incontinence and/or a validated symptom score that included questions on urgency and/or urge incontinence. If a study failed to assess any of these three criteria, the study was excluded as a measure of OAB efficacy, but could be included in an assessment of secondary OAB outcomes and adverse events. Author’s success was defined by whatever criteria was chosen by the investigators such as a reduction of urge incontinence episodes by 50%. Reviewer’s success is based upon how the results aligned with the methods and success criteria cited above.
Secondary outcome measures are useful from a clinical standpoint, but are not specific measures of OAB treatment efficacy. These include metrics of other OAB symptoms – urinary frequency and nocturia, non-specific LUTS questionnaires, quality of life, bother instruments and effects on physiological parameters such as uroflow (Q), post-void residual urine (PVR) and other urodynamic parameters.
All articles selected for the review were assessed for quality. A quantitative quality assessment tool adapted from Hartmann et al.* was utilized based on two broad sets of criteria: efficacy and safety. The efficacy score had a range of 0-20 and the safety criteria ranged from 0-16. The higher the score the better was the scientific quality of the study. An efficacy score of less than seven was considered to be scientifically invalid. A safety score of less than eight was considered unacceptable.

The database search retrieved 110 articles for review of which 26 met inclusion criteria by title and 14 by abstract, of which 11 were full text articles. Five studies were excluded leaving a total of 6 studies for systematic review.

The most glaring finding of this systematic review was the paucity of studies and the overall poor scientific quality of the studies. Only six of 110 articles met the inclusion criteria and only half of these included sufficient data to permit an assessment of success rate. Furthermore, there were major scientific limitations. None of the studies had a control group and, combining all studies, only 194 total patients were available for review. Furthermore, follow-up was extremely limited – 4 of 6 studies had a follow up of less than 6 months.  
On the positive side, all of the included studies were well designed except for the absence of controls, and all measured at least one of the reviewer’s primary outcome measures, i.e. urgency, urge incontinence episodes and/or validated questionnaires. Accordingly, reviewer and author success rates were identical, ranging from 62 – 83%, so it appears that neuromodulation has, at least  some short term effects on relieving OAB symptoms, but the data does not provide enough support for any long-term conclusions. Nevertheless, neuromodulation was deemed to be safe, with minimal adverse events reported, from 14 to 31%.

There is a serious paucity of quality studies regarding the efficacy of neuromodulation in patients with multiple sclerosis. Although the available data demonstrates short term improvement in overactive bladder symptoms in the majority of patients, the data is limited and does not provide enough evidence to permit robust conclusions.

Hartmann KE, McPheeters ML, Biller DH, et al. Treatment of overactive bladder in women. Evidence Report/technology Assessment. 2009 Aug(187):1-120, v. PMID: 19947666.

Continence 7S1 (2023) 100743
DOI: 10.1016/j.cont.2023.100743