Development of an implant technique and early experience using a novel implantable pulse generator with a quadripolar electrode array at the tibial nerve for refractory overactive bladder.

OBJECTIVES: Tibial nerve stimulation is an effective treatment for overactive bladder (OAB) and has been utilized as an in-person recurring session treatment option for many years. The primary objective of this study was to evaluate the safety and efficacy of a long-term implantable device and the method of utilizing a retrograde approach to place the device (a percutaneous implantable pulse generator [pIPG] with integrated quadripolar electrodes) at the tibial nerve (Protect PNS; Uro Medical Corp.). METHODS: A novel retrograde implant technique was developed through multiple cadaveric dissections to percutaneously implant a chronic, wireless, minimally invasive pIPG device with integrated quadripolar electrodes (now licensed to Uro Medical) at the tibial nerve. A proof-of-concept pIPG device approved as part of an FDA IDE was designed to gain early experience in subjects with refractory OAB. The pIPG was implanted in the office under local anesthesia using the novel retrograde approach, and stimulation was activated using an external wireless energy source called a transmitter. Initially, a pilot study was designed to compare outcomes in subjects randomized to either percutaneous tibial nerve stimulation (PTNS) or Protect PNS. However, due to the small sample sizes available at this time, it was not possible to compare the two groups. Thus, the purpose of this manuscript is to describe the outcome of subjects who underwent implantation of the Protect PNS system. Twelve-month safety and efficacy were evaluated. RESULTS: Nine subjects were enrolled in the randomized pilot study; 5 to the pIPG group and 4 to PTNS, and all completed the 13-week primary endpoint. Subsequently, two subjects in the PTNS group chose to cross over and have the pIPG implanted after 13 weeks. Outcomes of the seven subjects who underwent implantation of the pIPG are described. No complications related to the office procedure were noted. Two of the older model pIPG devices became nonresponsive at 1 and 4 weeks and were replaced. Six minor adverse events were reported and resolved. Subjects reported improvement in urge urinary incontinence (UUI) episodes, OAB symptoms, and quality of life. Subjects impanted with a pIPG reported a 50% reduction in UUI as early as 1 week. CONCLUSIONS: Results of this pilot study suggest that retrograde percutaneous implantation of a pIPG is a safe, minimally invasive one-stage office procedure for treatment for urge incontinence related OAB symptoms, without significant complications after 12 months follow-up. Future studies will be required to compare outcomes among treatment modalities.

Initial experience using a novel nerve stimulator for the management of pudendal neuralgia.

AIMS: In patients with pudendal neuralgia, prior studies have shown efficacy in chronic stimulation with Interstim® (Medtronic, Inc.). This feasibility study reports on the initial experience of using a wireless system to power an implanted lead at the pudendal nerve, StimWave®, to treat pudendal neuralgia. METHODS: Retrospective chart review identified patients with a lead placed at the pudendal nerve for neuralgia and powered wirelessly. Clinical outcomes were assessed at Postoperative visits and phone calls. Administered non-validated follow-up questionnaire evaluated the Global Response Assessment, percentage of pain improvement, satisfaction with device, and initial and current settings of the device (h/day of stimulation). RESULTS: Thirteen patients had the StimWave® lead placed at the pudendal nerve, 12 (92%) female and 1 (7.6%) male. Mean age was 50 years (range: 20-58). Failed prior therapies include medical therapy (100%), pelvic floor physical therapy (92%), pudendal nerve blocks (85%), pelvic floor muscle trigger point injections (69%), neuromodulation (30.7%), or surgeries for urogenital pain (23.1%). After the trial period, 10/13 (76.9%) had >50% improvement in pain with 6/13 (46.1%) reporting 100% pain improvement. Nine underwent permanent lead placement. At last postoperative visit (range, 6-83 days), 5/9 patients reported >50% pain improvement. Seven patients reached for phone calls (22-759 days) reported symptoms to be "markedly improved" (n = 2), "moderately improved" (n = 4), or "slightly improved" (n = 1). At follow up, complications included lead migration (n = 2), broken wire (n = 1), or nonfunctioning antenna (n = 2). CONCLUSION: Complex patients with pudendal neuralgia may benefit from pudendal nerve stimulation via StimWave®.

A Novel Approach to Managing Post Retropubic Vaginal Sling Pain.

OBJECTIVE: To describe a novel technique of using peripheral nerve neuromodulation (PNNM) for the treatment of refractory, mesh-induced chronic pelvic pain. Chronic pelvic pain associated with mesh can be a debilitating complication and there is currently no consensus on treatment. PNNM has been shown to be successful in the treatment of post-traumatic neuralgias but has yet to be studied in mesh complications. MATERIALS AND METHODS: We present a case of a 50-year-old woman who had unrelenting pelvic pain after retropubic sling placement. She failed multiple therapies including medications, mesh removal, pelvic floor physical therapy, pudendal neuromodulation, and pelvic floor onabotulinumtoxinA trigger point injections. RESULTS: The only treatment that provided temporary relief of this patient's pain was transvaginal trigger point injections along with a right pudendal nerve block using 40 mg triamcinolone and 0.5% ropivacaine. To help define if treatment at the site of her pain would provide relief, a series of blocks were done by advancing a needle retropubically to her area of pain and injecting triamcinolone and 0.5% ropivacaine. This injection, which corresponded to the previous tract of her retropubic sling, provided temporary, but profound, relief. PNNM was then done with placement of the electrode in the retropubic space at the site of her pain. This provided instantaneous relief of almost all of her pain symptoms. Twelve months postoperatively, the patient continued to have >90% improvement in her pain. CONCLUSION: Focused PNNM is a simple procedure and can provide symptomatic relief for refractory postvaginal mesh pain.

Transvaginal Trigger Point Injections Improve Pain Scores in Women with Pelvic Floor Hypertonicity and Pelvic Pain Conditions.

OBJECTIVES: Chronic pelvic pain in women often requires multimodal treatment regimens. We describe our method of transvaginal trigger point injections (TPIs) and report outcomes using change in pain scores. METHODS: This was a retrospective review of women treated with in-office pelvic floor muscle injections from January 2012 to August 2015. Lidocaine 1% and 2%, bupivacaine 0.5%, or ropivacaine 0.5% with or without the addition of triamcinolone 40 mg was used for the injections. Pain was reported on a 0- to 10-point numerical rating scale before and after injection. Differences in pretreatment and posttreatment pain scores were analyzed after the first injection and after subsequent injections. Repeated-measures analysis was used to determine if any variable affected treatment response. RESULTS: One hundred one women with a mean age of 44 years had a total of 257 separate visits for pelvic floor muscle injections. Triamcinolone was used at 90.2% (230/255) of the TPI visits. After the initial TPI visit, there was significant decrease in total levator numerical rating scale score (maximum score, 20; mean, -6.21 ± 4.7; P < 0.0001), and 77% (70/91) of patients had improved. These significant improvements were noted at all visits 1 through 4 and whether bilateral or unilateral injections were done. Only the total amount of local anesthestic used had a significant effect on the change in total levator pain scores (P = 0.002). Minor adverse effects including leg numbness, dizziness, nausea, bleeding, and headache occurred at 10% of visits. CONCLUSIONS: Pelvic floor muscle injections decrease pain levels in women with pelvic floor dysfunction.

Does sex matter? A matched pairs analysis of neuromodulation outcomes in women and men.

AIMS: To evaluate whether baseline symptoms and outcomes are influenced by gender in a matched cohort undergoing neuromodulation. METHODS: Patients in our prospective neuromodulation database that had a tined lead placed were reviewed. Those that had implantable pulse generator (IPG) placed were matched on age and urologic diagnosis. History, voiding diaries, satisfaction, Interstitial Cystitis Symptom/Problem Index (ICSIPI), and overactive bladder symptom severity (OABq ss)/health-related quality of life (HRQOL) preimplant and over 3 years were evaluated using descriptive statistics, repeated measures, and matched pair GEE or mixed analyses. RESULTS: Of 590 patients in the database, more women than men received an IPG (450/488; 92.2 vs. 84/102; 82.4%; p = 0.0011). Eighty matched pairs (n = 160; 81% ≥ 50 years old; 56.25% had urgency/frequency with urge incontinence-UI) were identified and evaluated. On voiding diaries, volume/void was greater in women only at baseline (p = 0.040); both groups improved over time (p < 0.0001). Urinary frequency improved in both women and men (p = 0.0010; p = 0.0025). Over 3 years, UI episodes/day improved only in men (p = 0.017) and UI severity improved only in women (p < 0.0001). ICSIPI, OABq ss, and HRQOL scores improved similarly in both groups (p < 0.0001 for all measures in both groups), and although more women were satisfied at 3 months (p = 0.027), groups did not differ at other time points. CONCLUSIONS: More women undergo neuromodulation and have initial success and subsequent IPG implantation. UI episodes improved only in men, and UI severity improved only in women. Both women and men experienced similar levels of symptom improvement on other measures.

Percutaneous Tibial Nerve Stimulation in the Office Setting: Real-world Experience of Over 100 Patients.

OBJECTIVE: To examine the outcomes and compliance with percutaneous tibial nerve stimulation (PTNS) for overactive bladder (OAB) symptoms. METHODS: Adults who had PTNS from June 30, 2011, to October 8, 2015, were retrospectively reviewed for demographics, copay, travel distance, employment status, history, symptoms, and treatments used before, during, and after PTNS. Pearson chi-square test, Fisher exact test, Wilcoxon rank and paired t test were performed. RESULTS: Of 113 patients (mean age 75 ± 12 years), most were women (65.5%), married (78.1%), and retired or unemployed (80.2%). The median distance to the clinic was 8.1 mi, and the median copay was $0. The most common indication for PTNS was nocturia (92.9%) followed by OAB with urgency urinary incontinence (75.2%) and urinary urgency and/or frequency (24.8%). Prior treatments included anticholinergics (75.2%), mirabegron (36.6%), behavioral modification (29.2%), pelvic floor physical therapy (18.6%), and others (19.5%). Patients completed a mean of 10.5 ± 3 of 12 planned weekly PTNS treatments. Of 105 patients, 40 (38.1%) used concomitant treatments (most commonly anticholinergics). Of 87 patients, 62 (71.3%) had decreased symptoms at 6 weeks, and of 85 patients, 60 (70.6%) had decreased symptoms at 12 weeks. The majority (82; 75.6%) completed all 12 weekly treatments and 45 (54.9%) completed 3 (median) monthly maintenance treatments. The most common reason for noncompliance was lack of efficacy. Visit copay, employment status, and distance to the clinic were not associated with failure to complete weekly treatments or progression to monthly maintenance. CONCLUSION: Although most patients' symptoms decreased after weekly PTNS, nonadherence to maintenance and lack of efficacy may limit long-term feasibility. Copay and distance traveled were not associated with noncompliance.

Pudendal Neuromodulation as a Treatment for Persistent Genital Arousal Disorder-A Case Series.

BACKGROUND: Persistent genital arousal disorder (PGAD) is a rare life-altering condition characterized by unwanted, uncomfortable genital sensations or spontaneous orgasms without physical or emotional stimulation. Its etiology remains unclear, and a variety of treatments have been attempted with incomplete resolution. We propose that chronic pudendal neuromodulation (CPN) may be a useful treatment for PGAD symptoms. METHODS: A retrospective chart review was performed for women older than 18 years with a diagnosis of PGAD that had staged neuromodulation with placement of a tined lead at the pudendal nerve. Demographic, operative, and postoperative data were collected. A survey was then sent to these women to assess additional demographic data, preoperative and postoperative symptoms, and patient satisfaction. Descriptive statistics were performed. RESULTS: Six women underwent CPN for PGAD. Mean age was 52 (SD, 9) years. Five (83%) of 6 were still implanted at time of survey, at a mean of 38 months after implantation; 1 device was removed for nonuse. Four of 6 completed surveys and were still using their device. Three of 4 had met their treatment goals and were satisfied with CPN; 3 of 4 felt CPN was the most useful treatment modality they had used overall. Chronic pudendal neuromodulation also improved chronic pelvic pain (4/4), bowel function (3/4), and bladder function (3/4). CONCLUSIONS: Chronic pudendal neuromodulation can be an effective treatment for decreasing frequency of PGAD symptoms and providing symptom relief.

The Impact of Baseline Functional Bladder Capacity on Short-term Neuromodulation Outcomes.

OBJECTIVE: To evaluate the impact of functional bladder capacity (FBC) on clinical outcomes after a staged neuromodulation procedure. MATERIALS AND METHODS: Adults in our prospective neuromodulation database were evaluated. Data were collected from medical records, voiding diaries (FBC defined as average volume per void), Interstitial Cystitis Symptom Index-Problem Index, Overactive Bladder Questionnaire, and Global Response Assessment over 3 months. Descriptive statistics, Pearson's chi-square tests, Wilcoxon rank sum tests, logistic regression, repeated measures analyses, and Spearman correlation coefficients were performed. RESULTS: Of the 216 patients (mean age 59 years; 84% female), most had urinary urgency and frequency with or without urge incontinence (71%), a sacral lead placement (82%), and implantable pulse generator (IPG) implantation (92%). Baseline FBC was similar between implanted and not implanted patients (P = .17); however implanted patients had a median 19 mL increase in FBC after lead placement compared to a 2.7 mL decrease in explanted patients (P = .0014). There was a strong association between percent change in FBC after lead placement and IPG implantation (P = .021; C-statistic 0.68), but baseline FBC (mL) was not associated. Baseline FBC (mL), or percent change in FBC after lead placement, was not related to symptom improvement. When grouped by baseline FBC < 150 mL and FBC ≥ 150 mL, FBC only improved significantly in the <150 group but both demonstrated significant improvements in symptoms. CONCLUSION: FBC improvements were associated with IPG implantation but not other symptom measures. Patients with low FBC (baseline FBC < 150) also achieved significant improvements in symptoms.

The impact of prior back surgery on neuromodulation outcomes: A review of over 500 patients.

AIMS: To evaluate neuromodulation outcomes in patients with prior back surgery. METHODS: Adults in our prospective observational sacral/pudendal neuromodulation study were retrospectively evaluated. History and operative details were reviewed, and outcomes were measured at 3, 6, 12, and 24 months with overactive bladder questionnaire (OAB q) symptom severity (SS)/health related quality of life (HRQOL), interstitial cystitis symptom/problem indices (ICSI - PI), voiding diaries, and global response assessments (GRA). Data were examined with Pearson's χ2 , Fisher's exact, Wilcoxon rank sum tests, and logistic regression multivariate analysis. RESULTS: Five hundred and sixty patients were evaluated (mean age 58.8 ± 17 years; 83% female; 79% had a sacral lead placed), 109 (19%) had history of back surgery; 66 surgeries were lumbar. Back surgery patients were older (mean 63 ± 15 vs. 58 ± 17 years; P = 0.003) and a higher proportion had urge urinary incontinence (UUI) (64% vs. 50% P = 0.008). Generator implant rates were similar (94% vs. 91%; P = 0.34). OABq-SS and HRQOL and ICSI - PI composite scores did not differ between groups at any time point. On bladder diaries, median incontinence episodes daily at baseline and between stages were worse in the prior back surgery group but all bladder diary parameters improved significantly in both groups with the exception of mean voided volume which only improved significantly in the non-back surgery group. Most patients in both groups reported moderate/marked improvement in overall bladder symptoms. CONCLUSIONS: This study suggests that prior back surgery does not appear to impact clinical outcomes; therefore, neuromodulation may be offered in this patient population.

Predictors of reoperation after sacral neuromodulation: A single institution evaluation of over 400 patients.

AIMS: To explore factors that may predispose patients to reoperation after sacral neuromodulation (SNM). METHODS: Patients enrolled in our longitudinal neuromodulation database were reviewed. Medical records data, and voiding diaries, Interstitial Cystitis Symptom-Problem Indices (ICSI-PI), and Overactive Bladder Questionnaires (OAB-q) at baseline and 3 months were analyzed with Pearson's χ2 , Fisher's Exact test, Wilcoxon rank tests, and multivariable logistic regression. RESULTS: Of 407 patients, 134 (33%) had at least one reoperation over median 28.9 months follow-up (range 1.6-121.7); 78/407 (19%) were revised, and 56/407 (14%) were explanted. The most common reason for reoperation was lack of efficacy/worsening symptoms (n = 87). The reoperations group had a higher proportion of women (P = 0.049), lower mean body mass index (BMI; P = 0.010), more reprogramming events (P < 0.0001), longer median follow-up (P = 0.0008), and higher proportions with interstitial cystitis (P = 0.013), using hormone replacement therapy (P = 0.0004), and complications (P < 0.0001). Both reoperations/no reoperations groups had similar improvements in ICSI-PI (P < 0.0001 for both), OAB-q severity (P < 0.0001 for both) and quality of life (P < 0.0001 for both). On multivariate analysis, only longer follow-up (P = 0.0011; OR 1.048; CI 1.019, 1.078) and having a complication (P < 0.0001; OR 23.2; CI 11.47, 46.75) were significant predictors of reoperations. In women only, using HRT at time of implant was also predictive of reoperation (P = 0.0027; OR 3.09; CI 1.48, 6.46). CONCLUSIONS: In this largest known series to date, one third of the patients required reoperation and the most common reason was lack of efficacy/worsening symptoms. Ongoing study is needed as the technology continues to evolve. Neurourol. Urodynam. 36:354-359, 2017. © 2015 Wiley Periodicals, Inc.

Outcomes of Sacral Neuromodulation in Patients with Prior Surgical Treatment of Stress Urinary Incontinence and Pelvic Organ Prolapse.

OBJECTIVES: The aim of this study was to evaluate the efficacy of sacral neuromodulation in patients with prior stress urinary incontinence (SUI) or pelvic organ prolapse (POP) surgery. METHODS: Women in our prospective neuromodulation database were evaluated. Patients with a history of prior SUI/POP surgery were compared to those without. Medical records at baseline were reviewed, and primary outcome was defined as moderate/marked improvement on Global Response Assessment (GRA) at 3 months. Secondary outcomes were measured using bladder diaries and Overactive Bladder Symptom Severity (OABq-SS)/health-related quality of life (HRQOL). Data were analyzed with Pearson χ test, Fisher exact test, Wilcoxon rank-sum test, and repeated-measures analyses. RESULTS: Of 210 subjects, 108 (51%) had prior SUI/POP surgery. Patients with SUI/POP surgery had more prior hysterectomies. At 3 months, there was no difference between groups on GRA outcomes. On the bladder diary, both groups had improvement in median voids per 24 hours, urgency severity, and urge incontinence over 2 years. On the GRA, fewer patients in the SUI/POP group were treatment responders at 12 and 24 months. For urinary urgency, a few in this group were moderately/markedly improved at 6 months, and a higher proportion are reported still leaking urine at 6 and 12 months. Similar proportions in each group reported moderate/marked improvement in leaking. Satisfaction was similar between groups. The OABq-SS/HRQOL scores improved, and there was no difference between the groups. CONCLUSION: Sacral neuromodulation improves bladder symptoms in women with prior SUI/POP surgery, but response may be slightly less in those with prior surgery due to underlying bladder or pelvic floor issues.

Treatment of ulcerative compared to non-ulcerative interstitial cystitis with hyperbaric oxygen: a pilot study.

BACKGROUND: The etiology of interstitial cystitis (IC) is often idiopathic but can be due to Hunner's ulcers. Hyperbaric oxygen (HBO) is used to treat ulcerative disease of the superficial skin. We hypothesized that HBO can treat ulcerative IC (UIC) but would be less efficacious for non-ulcerative IC (NIC). METHODS: Patients with NIC and UIC enrolled in this study. Following informed consent, demographic information was collected. A visual analog pain scale and validated questionnaires were collected; each patient underwent cystoscopy prior to treatment. Each subject met with a hyperbaric specialist and after clearance underwent 30 treatments over 6 weeks. Adverse events were monitored. Patients repeated questionnaires, visual analog pain scale and global response assessment (GRA) immediately, 2 weeks, 3, 6 and 12 months after treatment. Patients also underwent cystoscopy 6 months after treatment. Differences before and after treatment were compared. RESULTS: Nine patients were recruited to this study. One was unable to participate, leaving two subjects with NIC and six with UIC. All patients completed HBO without adverse events. Three patients completed HBO but pursued other therapies 7, 8.5 and 11 months after treatment. On GRA, 83% of patients with UIC were improved. This treatment effect persisted, as 66% of UIC patients remained better at 6 months. In contrast, only one patient in the NIC group improved. Questionnaire scores improved in both groups. Pain scores improved by 2 points in the UIC group but worsened by 1.5 points in the NIC group. Two patients with ulcers resolved at 6-month cystoscopy. CONCLUSION: HBO appeared beneficial for both UIC and NIC. Data shows slightly better benefit in patients with UIC compared to NIC; both groups showed improvement. Given the small sample size, it is difficult to draw definitive conclusions from these data. Larger studies with randomization would be beneficial to show treatment effect.

Novel Use of Pudendal Neuromodulation in a Pediatric Patient With Caudal Regression and Partial Sacral Agenesis for Refractory Bowel Bladder Dysfunction.

Sacral neuromodulation (SNM) has been used off-label in the United States for over a decade in the pediatric population. Many published studies have demonstrated efficacy with SNM in this population; however, a significant number of children with refractory bowel bladder dysfunction (BBD) also have underlying comorbidities. Children with certain spinal abnormalities pose a problem for the urologist treating BBD. Patients with caudal regression can have various sacral anomalies, making SNM challenging or impossible. We present the first case in the United States of pudendal neuromodulation in a pediatric BBD patient with caudal regression.

Number of active electrodes at time of staged tined lead interstim implant does not impact clinical outcomes.

OBJECTIVES: To determine: (1) if obtaining motor response on <4 tined lead electrodes at time of placement affects subjective and objective clinical outcome and (2) voltage requirements to elicit motor response at implant and first postoperative visit number based on number of responding electrodes. METHODS: We reviewed our prospective neuromodulation database to identify patients with unilateral S3 lead placement and motor response (bellows ± toe flexion) on stimulation of 1-4 electrodes, then grouped by number of active electrodes at lead placement. Stage 1 success, reoperation and reprogramming rates, mean voltage at implant and first postoperative visit, and Interstitial Cystitis Symptom/Problem Indices (ICSI-PI) were analyzed using Pearson's Chi-square, Fisher's exact, Kruskal-Wallis or Wilcoxon rank tests. RESULTS: Two hundred forty four patients met inclusion criteria, categorized into 1-2 (n = 25), 3 (n = 48), and 4 active electrodes (n = 171). There were no significant differences between groups in terms of age, indications for neuromodulation, or stage 1 success. At implant, patients with <4 active electrodes required higher mean voltages for motor responses (5.9, 4.9, and 3.9 volts for each group respectively; P < 0.0001). Mean voltages for sensory threshold at first postoperative programming were 1.5 ± 1.5, 0.9 ± 1.0, and 0.8 ± 1.0, respectively (P = 0.08). Overall reoperation rates, and reprogramming sessions at 24 months did not differ (P = 0.72 and P = 0.50). ICSI-PI scores improved similarly in all groups. CONCLUSIONS: Motor response on four electrodes is not necessary for successful stage 1 trial. Despite higher voltage requirements in those with <4 active electrodes at implant, this difference was not observed at initial postoperative programming. Neurourol. Urodynam. 35:625-629, 2016. © 2015 Wiley Periodicals, Inc.

Effect of Sacral Neuromodulation on Outcome Measures and Urine Chemokines in Interstitial Cystitis/Painful Bladder Syndrome Patients.

OBJECTIVES: Sacral neuromodulation (SNM) may improve interstitial cystitis/painful bladder syndrome (IC/BPS) symptoms of urinary frequency, urgency and perhaps even pain, but objective measures of improvement are lacking. We evaluated the potential for urinary chemokines to serve as measures of treatment response over time to SNM. METHODS: Women with IC/BPS undergoing SNM consented for this study. Three-day bladder/pain diaries were collected at baseline and validated Interstitial Cystitis Symptom Problem Index (ICSPI) scores and mid-stream urine specimens were collected at baseline and at 24 weeks after successful implant. Collected urine was screened for infection by dipstick and analyzed for chemokines by luminex xMAP analysis. RESULTS: At baseline (n = 16), urine levels of CXCL-1 positively correlated with pain score (r = 0.63, P = 0.009), urgency (r = 0.61, P = 0.01), ICSPI (r = 0.43, P = 0.09) and daily voids (r = 0.44, P = 0.08). ICSPI and pain scores also positively correlated with sIL-1ra (r = 0.50, P = 0.04) and monocyte chemotactic protein-1 (MCP-1) or CCL2 positively correlated with daily voids (r = 0.45, P = 0.07) only. At 24 weeks, the median ICSPI index fell from 28 to 15 (n = 7, P = 0.008). Urine levels of sIL-1ra (633.8 ± 188.2 vs. 149.9 ± 41.62 pg/mL) and MCP-1 (448.3 ± 11.6 vs. 176.9 ± 46.16 pg/mL) and CCL5 (20.78 ± 4.09 vs. 11.21 ± 4.12 pg/mL) were also significantly reduced at the follow-up relative to baseline values (P = 0.04). Multivariable analysis of data revealed that sIL-1ra and MCP-1 together explained the majority of variance in data. Levels of CXCL-1, CXCL-10, interleukin (IL)-8, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) were also reduced at 24 weeks, but differences were not significant. CONCLUSIONS: Concomitant decrease in urine levels of chemokines especially MCP-1 was associated with treatment response of SNM. These results support the role of chemokines as downstream effectors of neuromodulation response and could serve as potential non-invasive measures of treatment response. CLINICAL TRIAL REGISTRATION NUMBER: NCT01739946.

Pilot Study Exploring Chronic Pudendal Neuromodulation as a Treatment Option for Pain Associated with Pudendal Neuralgia.

OBJECTIVES: Pudendal neuralgia can cause significant voiding and pain symptoms. We explored the effects of chronic pudendal neuromodulation (CPN) and nerve blocks on pain associated with pudendal neuralgia. METHODS: Patients with pudendal neuralgia and tined lead placed at the pudendal nerve were reviewed. History and initial improvement after lead placement were collected from medical records. Demographics, symptom characteristics and changes after various treatments were assessed by mailed survey. Descriptive statistics were performed. RESULTS: Of 19 patients (mean age 54.8 years, 63% female), 6/19 (32%) had previous sacral neuromodulation. Before CPN, 18 patients had 77 nerve blocks (median six blocks per patient); most blocks (60/77; 78%) provided at least some relief. After lead placement, pain relief was complete in three patients, almost complete in three, significant/remarkable in 10, and small/slight in three. All 19 patients had a permanent generator placed. Five were ultimately explanted at (mean) 2.95 years: one had total symptom resolution, one had stopped using the device, and three lost efficacy. Survey respondents (n = 10) indicated that they had been experiencing pain for (median) 4.42 years before CPN. The most helpful pain treatment cited was medication for 6/10 and neuromodulation for 4/10; 8/9 rated neuromodulation as more helpful than nerve block, while one subject felt that the two treatments were equally helpful. Compared to sacral neuromodulation, 3/4 rated CPN as more effective for pain. Overall, 8/10 were satisfied with CPN; only 1/9 was mildly satisfied with nerve block. CONCLUSIONS: Chronic pudendal neuromodulation can improve pain in patients with pudendal neuralgia.

Percutaneous tibial nerve stimulation and sacral neuromodulation: an update.

Neuromodulation is an important treatment modality for a variety of pelvic floor disorders. Percutaneous tibial nerve stimulation (PTNS) and sacral neuromodulation (SNM) are currently the two approved methods for delivering this therapy. Percutaneous tibial nerve stimulation is a minimally invasive office-based procedure that has shown efficacy in the treatment of overactive bladder, fecal incontinence, and pelvic pain. It has the advantage of minimal side effects but is limited by the need for patients to make weekly office visits to receive the series of treatments. Sacral neuromodulation uses an implanted device that stimulates the S3 nerve root and can improve symptoms of overactive bladder, non-obstructive urinary retention, fecal incontinence, and pelvic pain. This paper will review the most recent literature regarding this topic and discuss their advantages and limitations and recent innovations in their use.

Proof of concept trial on changes in current perception threshold after sacral neuromodulation.

OBJECTIVES: Sacral neuromodulation (SNM) is theorized to alter the neural pathways that mediate bladder and urethral sensation. We hypothesize that SNM affects current perception thresholds (CPTs) of afferent sensory nerve pathways. MATERIALS AND METHODS: Eight women were enrolled and completed pre and postoperative testing. A CPT device was used to measure CPT at 5 Hz (C-fibers), 250 Hz (Aδ-fibers), and 2000 Hz (Aß-fibers) on the urethra and bladder prior to and one month after SNM. Index finger readings at 2000 Hz served as controls. RESULTS: SNM had the greatest effect on the bladder at 250 and 2000 Hz, suggesting reduced bladder sensitivity. Significant changes in CPT were seen in the bladder at 2000 Hz with a decrease in sensitivity (p = 0.033). CPT testing was well tolerated, and no adverse events were identified. CONCLUSIONS: With a measurable change in CPT values for Aδ-fibers and Aß-fibers, these findings suggest that SNM modulates large myelinated afferent fibers in the bladder. Notably, little or no changes were found in the C-fiber CPT measurements. More research is needed with a larger sample size to determine the significance of these findings.

Understanding clinic options for overactive bladder.

Overactive bladder (OAB) is a symptom complex of urinary frequency, nocturia and urgency with or without urgency incontinence that adversely impacts patient's quality of life. Conservative management begins in the outpatient clinic, often with significant improvement and patient satisfaction. In this review we will discuss the evaluation of OAB and review treatment options focusing on behavioral modification, medical therapy, and neuromodulation. These treatment options are offered in a stepwise fashion, remembering that more than one may be needed and can be used concomitantly.