INTRODUCTION
Neurogenic lower urinary tract dysfunction (NLUTD) refers to voiding dysfunction as a result of a neurologic insult [1, 2]. Symptoms of NLUTD depend on the site of neurologic insult and can include detrusor overactivity, atony, loss of sphincter coordination, pain, and urinary retention [1–3]. Millions of patients worldwide suffer from neurological disorders that can affect the lower urinary tract [4]. As many as 72% of Parkinson disease patients and 90% of patients with multiple sclerosis experience NLUTD [5]. As such, there is an immediate need to address the urinary complications in this large patient population.
First-line therapy for neurogenic detrusor overactivity includes anticholinergics and beta-3 agonists. Anticholinergic medications, which work by blocking the neurotransmitter acetylcholine, carry several risks when used chronically. Long-term compliance is generally low due to the intolerable side effects of dry eyes, dry mouth, and constipation [6]. Several anticholinergics cross the blood-brain barrier and accumulate in the central nervous system, leading to adverse effects on brain function and an increased risk of dementia [7].
Intradetrusor onabotulinum toxin A (OnA) is a U.S. Food and Drug Administration-approved treatment option for patients with NLUTD who have failed first-line therapy with medications. The primary benefits of this treatment are an improvement in bladder capacity and a reduction in the number of urinary incontinence episodes. However, it does require repeat injections approximately every 6–9 months to maintain its effectiveness [8]. Treatment with intradetrusor OnA also carries a risk of urinary retention ranging from 15%–44% in patients with NLUTD, depending on the dose [9]. Additionally, patients with some neurologic diagnoses may utilize OnA for treatment of other medical conditions, which can limit the amount available for injection in the bladder.
Implantable neuromodulation is an additional option for the treatment of non-NLUTD. Patients with NLUTD were not included in the original neuromodulation trials as it was believed that an intact neural system was required for neuromodulation to be effective [10]. However, neuromodulation has been shown to improve voiding symptoms in patients with various neurologic disorders including multiple sclerosis and Parkinson disease [11]. Previously, a major deterrent to implantable devices in neurologic patients was the need for possible magnetic resonance imaging (MRI) monitoring of their disease. However, the newest implantable sacral neuromodulation (SNM) devices are now MRI conditional [12]. Despite this advancement, data regarding the use and effectiveness of neuromodulation for NLUTD are still lacking. We aim to describe our experience using sacral and pudendal neuromodulation to treat patients with neurogenic bladder.
METHODS AND MATERIALS
Patient Population
A retrospective chart review of electronic medical records at a single institution for patients from 2008 to 2020 with an ICD-9/10 (International Classification of Diseases, Ninth Revision/ 10th Revision) code of “neurogenic bladder” undergoing implantable neuromodulation was performed. Neuromodulation was performed in 2 stages. Neuromodulation lead placement and stimulation for one week with a temporary external generator is stage 1, and stage 2 is implantable pulse generator (IPG) placement. Patients with urinary retention or fecal incontinence underwent a 2-week stage 1 trial. Patients undergoing stage 1 and stage 2 neuromodulation were included for study. Patients who reported greater than 50% improvement in their baseline symptoms after stage 1 implant advanced to IPG placement (stage 2 implantation).
Clinical Data Collection
Demographic and clinical data were collected. Clinical data obtained includes: the neurologic diagnosis associated with the patient’s lower urinary tract symptoms, the patient’s voiding symptoms (urinary urgency, urge urinary incontinence, or urinary retention), presence of fecal incontinence, duration and characterization of presenting lower urinary tract symptoms, symptoms after stage 1 implantation, prior and concomitant interventions including prior neuromodulation attempts, and patient-reported symptom change. Lead placement site was identified, and change in voiding symptoms after stage 1 implant was quantified based on sacral or pudendal lead placement. In patients with a prior history of neuromodulation, data on the most recent lead placement was included in this study.
RESULTS
Patient Population and Baseline Symptoms
We identified 82 patients with neurogenic bladder who underwent implantable sacral or pudendal neuromodulation. Among these, 55 were female (67.07%) and 27 were male (32.93%). The most common neurologic diagnoses included diabetic cystopathy (17.07%), spinal surgery (17.07%), and spinal cord injury (12.20%) (Table 1).
Voiding symptoms included urinary urgency in 46 (57.5%), urinary urgency as well as urgency urinary incontinence in 44 (55.0%), and urinary retention in 36 patients (45.0%). A total of 16 patients (19.5%) presented with both urgency urinary incontinence and urinary retention. Among patients with urinary retention, 32 (88.9%) performed clean intermittent catheterization (CIC) prior to neuromodulation. Nine patients (11.3%) reported fecal incontinence in addition to voiding symptoms. Additional presenting symptoms included nocturia in 15 patients (18.8%), straining to void in 14 patients (17.5%), and pelvic pain in 7 patients (8.8%).
Prior failed interventions were reported in 65 patients, and included oral anticholinergics or β3-agonists in 34 patients (41.46%), bladder chemodenervation in 12 patients (14.63%), and percutaneous tibial nerve stimulation in 2 patients (2.44%). Twenty-nine patients (35.37%) had more than one prior intervention. Twenty-two patients (26.83%) presented for repeat neuromodulation –20 with prior sacral and 2 with prior pudendal neuromodulation. A total of 17 patients did not have prior interventions, including 8 patients who underwent neuromodulation as first-line therapy for NLUTD, and one who received anticholinergic therapy concomitant with neuromodulation as first-line therapy. We identified 8 patients who were utilizing other therapies at the time of first stage neuromodulation, however prior records were unavailable for review.
Symptom Changes With Neuromodulation
Most recent stage 1 lead placement was sacral in 57 patients (69.51%) and pudendal in 25 patients (30.49%). Indications for pudendal lead placement included failed prior SNM trial, significant concomitant pelvic pain, and abnormal sacral anatomy secondary to spina bifida.
Among the 3 patients with spina bifida, 2 were female and one was male. After stage 1 lead placement, both female patients reported >50% improvement in urinary urgency, frequency, and urgency incontinence and continued to stage 2 IPG implantation. The male patient, whose chief complaint was urinary retention, reported improved bladder sensation but did not have improvement in intermittent catheterization volumes.
Symptom change after stage 1 implantation was subjectively reported in 69 patients (Fig. 1). Urinary urgency resolved in 1 patient, while 38 had over 50% improvement, 6 had less than 50% improvement, and 2 had worsening urgency. Urgency urinary incontinence resolved in 1 patient; 33 had over 50% improvement, and 7 had less than 50% improvement. Nocturia resolved in 1 patient with 15 having over 50% improvement. Straining to void improved over 50% in 10 patients. Three patients had over 50% improvement in pelvic pain and 4 had less than 50% improvement. Fecal incontinence improved over 50% in 6 patients, while 3 had less than 50% improvement. Among patients with urinary retention requiring CIC, 22 patients (75.86%) reported an objective decrease in postvoid CIC volumes of 50% or more.
Overall, 59 patients (71.95%) reported over 50% improvement in symptoms and advanced to stage 2 IPG placement. Of these patients, 24 underwent concomitant therapies with neuromodulation: 14 patients took oral medications, 4 patients underwent bladder chemodenervation, 4 patients utilized pelvic floor directed therapies (including vaginal suppositories, pelvic floor trigger point injections, pudendal nerve blocks, or pelvic floor chemodenervation), 1 patient underwent transurethral resection of the prostate, and 1 underwent suprapubic catheterization. Amongst patients who underwent stage 1 sacral lead placement, 72% advanced to stage 2. Of those who underwent stage 1 pudendal lead placement, 76% advanced to stage 2 IPG placement.
Among the 22 patients who underwent repeat neuromodulation, 20 advanced to stage 2. Reasons for failure include lead migration in 1, requirement for MRI in 2, and IPG battery failure in 4, and a decrease in previously established treatment efficacy in 15 patients. All newly placed neuromodulation units underwent changes in stimulation mode according to the patient’s response. Lead placement was changed in 11 patients, with 9 sacral leads changed to pudendal leads, 1 pudendal lead exchanged for a sacral lead, and 1 replaced pudendal lead. Along with repeat neuromodulation, 3 patients underwent concomitant bladder chemo-denervation and 2 patients underwent pelvic floor directed therapies including trigger point injections and bilateral pudendal nerve blocks.
DISCUSSION
This retrospective chart review demonstrates that neuromodulation can be an effective option for patients with NLUTD. Our findings are consistent with other studies. Lombardi et al. [13] performed SNM on 85 patients with incomplete spinal cord injury. Thirty-six (42.4%) responded to treatment with decreased catheterized volumes, fewer catheterizations, increased flow rates, and decreased postvoid residuals. Studies of similar methodology can be seen in Table 2 [4, 12–26]. Our study revealed success rates consistent with those previously reported with 72% of patients advancing to stage 2 IPG implant.
Van Ophoven et al. [27] in 2021 published a systematic review and meta-analysis. The authors investigated 47 studies on SNM in patients with NLUTD. The pooled success rate for SNM trial was 66.2% which included a total of 887 patients from 21 of these studies. We have a similar success rate of 70% for SNM in our cohort.
When used for the appropriate indications, pudendal neuromodulation proved to have similar or improved efficacy compared to SNM (76% vs. 70%) in our study population. While our institution’s default lead placement is in the S3 foramen, there are some instances where pudendal lead placement is preferred. Our findings implicate that when patients have abnormal sacral anatomy secondary to congenital malformations, have failed a trial of SNM, or have significant concomitant pelvic pain it is reasonable to consider pudendal neuromodulation with a likely successful outcome.
We identified 3 patients with spina bifida who experienced improvement in NLUTD symptoms with neuromodulation. Symptom improvement included decreased catheterization requirements, reduced pain and improvement in fecal incontinence. In a study of 29 patients with fecal incontinence associated with spina bifida, Chen et al. [14] demonstrated a significant decrease in neurogenic bowel dysfunction in patients who underwent neuromodulation. Our findings indicate neuromodulation is feasible, and should be an option for management of NLUTD in patients with spina bifida.
Limitations of this study include its retrospective nature. As such, we cannot investigate potential causality, delve deeply into patient history, and standardize data collection. The small sample size limits the generalizability of the findings. However, the sample size is on par with similar studies that investigate neuromodulation for the management of NLUTD. Additionally, the study was conducted at a single institution, which may restrict the diversity of the patient population.
It is important to acknowledge that due to the focus of our study on the short trial phase, long-term efficacy and adverse events were not specifically recorded or analyzed. In a subsequent meta-analysis that included SNM for nonneurogenic voiding symptoms, the incidence of adverse events was comparable to those reported in the van Ophoven meta-analysis. Therefore, it is reasonable to assume potential long-term adverse events would be consistent with other studies. This highlights the need for future research with prospective designs, larger sample sizes, multicenter collaborations, validated questionnaires, and longer follow-up periods to provide more robust and comprehensive evidence.
In conclusion, although implantable sacral and pudendal neuromodulation is not routinely utilized for the management of NLUTD, 72% of patients showed over 50% improvement in voiding symptoms during their stage 1 trial and advanced to stage 2 IPG placement. Given these findings, we advocate for the use of implantable neuromodulation for patients with a diagnosis of NLUTD.
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