Reduction of Overactive Bladder Medications in Spinal Cord Injury With Self-Administered Neuromodulation; a Randomized Trial.

PURPOSE: To evaluate if self-administered bladder neuromodulation with transcutaneous tibial nerve stimulation can safely replace overactive bladder medications in people with spinal cord injury. MATERIALS AND METHODS: We performed a 3-month, randomized, investigator-blinded, tibial nerve stimulation vs sham-control trial in adults with spinal cord injury and neurogenic bladder performing intermittent catheterization and taking overactive bladder medications. The primary outcome was a reduction in bladder medications while maintaining stable bladder symptoms and quality of life based on pre-post Neurogenic Bladder Symptom Score and the Incontinence-QOL questionnaire, respectively. Secondary outcomes included changes in pre-post cystometrogram, 2-day voiding diaries, and an anticholinergic medication side effect survey. RESULTS: Fifty people consented to the study, with 42 completing the trial. No dropouts were due to stimulation issues. All baseline demographics and surveys were comparable at baseline. Cystometrogram parameters were also comparable at baseline, except the stimulation group had a higher proportion of loss of bladder compliance compared to the control group. At the end of the trial, a significantly greater percentage of the tibial nerve stimulation group were able to reduce medications (95% v 68%), by a 26.2% difference in medication reduction (95% confidence interval 1.17%-51.2%). Function and quality of life surveys and cystometrograms at the end of the trial were alike between groups. Transcutaneous tibial nerve stimulation satisfaction surveys and adherence to protocol were high. CONCLUSIONS: In people with chronic spinal cord injury performing intermittent catheterization, transcutaneous tibial nerve stimulation can be an option to reduce or replace overactive bladder medications.

Efficacy and safety of tibial nerve stimulation using a wearable device for overactive bladder.

OBJECTIVE: To evaluate the efficacy and safety of a wearable, smartphone-controlled, rechargeable transcutaneous tibial nerve stimulation (TTNS) device in patients with overactive bladder (OAB). PATIENTS AND METHODS: This multicentre, prospective, single-blind, randomised clinical trial included eligible patients with OAB symptoms who were randomly assigned to the stimulation group or sham group. The primary efficacy outcome was change from baseline in voiding frequency/24 h after 4 weeks of treatment. The secondary efficacy outcomes included changes in bladder diary outcomes (urgency score/void, nocturia episodes/day, micturition volume/void, and incontinence episodes/day), questionnaires on Overactive Bladder Symptom Score (OABSS), Patient Perception of Bladder Condition (PPBC), and American Urological Association Symptom Index Quality of Life Score (AUA-SI-QoL) at baseline and after 4 weeks of treatment. Device-related adverse events (AEs) were also evaluated. RESULTS: In the full analysis set (FAS), the mean (sd) change of voiding frequency/24 h in the stimulation group and sham group at 4 weeks were -3.5 (2.9) and -0.6 (2.4), respectively (P < 0.01). Similar results were obtained in the per-protocol set (PPS): -3.5 (2.9) vs -0.4 (2.3) (P < 0.01). In the FAS and PPS, micturition volume/void significantly improved at 4 weeks (P = 0.01 and P = 0.02). PPBC improvement almost reached significance in the FAS (P = 0.05), while it was significant in the PPS (P = 0.02). In the FAS and PPS, AUA-SI-QoL significantly improved at 4 weeks in the two groups (P < 0.01 and P < 0.01), whereas there were no significant differences in urgency score/void, nocturia episodes/day or OABSS between the groups. Also, no device-related serious AEs were reported. CONCLUSIONS: The non-invasive neuromodulation technique using the novel ambulatory TTNS device is effective and safe for treating OAB. Its convenience and easy maintenance make it a new potential home-based treatment modality. Future studies are warranted to confirm its longer-term efficacy.

Effects of posterior tibial nerve stimulation (PTNS) on lower urinary tract dysfunction: An umbrella review.

BACKGROUND: Lower urinary tract dysfunction (LUTD) is a common, troublesome condition that often negatively affects patients' quality of life. Current literature has long been interested in how posterior tibial nerve stimulation (PTNS) can affect this condition. AIM: To extensively and systematically explore how PTNS affects LUTD based on the most recent systematic reviews. METHODS: A systematic search was conducted in PubMed, Scopus, Web of Science, and Embase according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. All the systematic reviews, with or without meta-analysis that assessed the effects of PTNS on LUTD were retrieved. The quality of the included studies was assessed using the Joanna Briggs Institute tool, and analysis was conducted using the Comprehensive Meta-Analysis version 3 tool. RESULTS: From a total of 3077 citations, 20 systematic reviews entered this study, and 13 of them included meta-analysis. The population of studies varied vastly, for instance, some studies included only children or women while other focused on a specific pathology like multiple sclerosis-induced neurogenic LUTD. The majority of included studies reported an overall improvement in LUTD following percutaneous PTNS, although admitting that these results were derived from moderate to low-quality evidence. CONCLUSION: The findings of this thorough umbrella review showed that the positive benefits of PTNS in treating LUTD are currently supported by low-quality evidence, and it is crucial to interpret them with great care.

Identification of brain functional connectivity during acute transcutaneous tibial nerve stimulation: A 3T fMRI study.

OBJECTIVES: A feasibility proof-of-concept study was conducted to assess the effects of acute tibial nerve stimulation (TNS) on the central nervous system in healthy volunteers using functional magnetic resonance imaging (fMRI). MATERIALS AND METHODS: Fourteen healthy volunteers were included in a prospective, single-site study conducted on a clinical 3T MRI scanner. Four scans of functional MRI, each lasting 6 min, were acquired: two resting-state fMRI scans (prior and following the TNS intervention) and in-between two fMRI scans, both consisting of alternating rest periods and noninvasive acute transcutaneous TNS (TTNS). Whole brain seed-based functional connectivity (FC) correlation analysis was performed comparing TTNS stimulation with rest periods. Cluster-level familywise error (FWE) corrected p and a minimal cluster size of 200 voxels were used to explore FC patterns. RESULTS: Increased FC is reported between inferior frontal gyrus, posterior cingulate gyrus, and middle temporal gyrus with the precuneus as central receiving node. In addition, decreased FC in the cerebellum, hippocampus, and parahippocampal areas was observed. CONCLUSIONS: Altered FC is reported in areas which have been described to be also involved in lower urinary tract control. Although conducted with healthy controls, the assumption that the underlying therapeutic effect of TNS involves the central nervous system is supported and has to be further examined in patients with incomplete spinal cord injury.

Shifts in patient preference of third-line overactive bladder therapy after introduction of the implantable tibial nerve stimulator.

INTRODUCTION: Third-line therapies for overactive bladder (OAB) that are currently recommended include intravesical Onabotulinumtoxin-A injections (BTX-A), percutaneous tibial nerve stimulation (PTNS), and sacral neuromodulation (SNM). The implantable tibial nerve stimulator (ITNS) is a novel therapy that is now available to patients with OAB. OBJECTIVE: The objective of this study was to analyze shifts in patient preference of third-line therapies for OAB after introducing ITNS as an option among the previously established therapies for non-neurogenic OAB. METHODS: A survey was designed and distributed via SurveyMonkey to the platform's audience of U.S. adults of age 18 and older. Screening questions were asked to include only subjects who reported symptoms of OAB. Descriptions of current AUA/SUFU guideline-approved third-line therapies (BTX-A, PTNS, and SNM) were provided, and participants were asked to rank these therapies in order of preference (stage A). Subsequently, ITNS was introduced with a description, and participants were then asked to rank their preferences amongst current guideline-approved therapies and ITNS (stage B). Absolute and relative changes in therapy preferences between stage A and stage B were calculated. Associations between ultimate therapy choice in stage B and participant characteristics were analyzed. RESULTS: A total of 485 participants completed the survey (62.5% female). The mean age was 49.1 ± 36.5 years (SD). The most common OAB symptoms reported were urgency urinary incontinence (UUI) (73.0%) and urinary urgency (68.0%). 29.2% of patients had tried medication for OAB in the past, and 8.0%-10.3% of patients were previously treated with a third-line therapy for OAB. In stage A, participants ranked their first choice of third-line therapy as follows: 28% BTX-A, 27% PTNS, and 13.8% SNM. 26.6% of participants chose no therapy, and 4.5% chose all three equally. In stage B, participants ranked their first choice as follows: 27.6% BTX-A, 19.2% PTNS, 7.8% SNM, and 19.2% ITNS. 21.9% of participants chose no therapy and 4.3% chose all four equally as their first choice. There were both absolute and relative declines in proportions of patients interested in BTX-A, SNM, and PTNS as their first choice of third-line therapy with the introduction of ITNS. Patients originally interested in PTNS in stage A had the greatest absolute change after the introduction of ITNS with 7.8% of participants opting for ITNS in stage B. Those interested in SNM in stage A had the largest relative change in interest, with 43.5% of those originally interested in SNM opting for ITNS in stage B. Finally, with the introduction of ITNS, the number of participants initially not interested in any third-line therapy declined by an absolute change of 4.7% and relative change of 17.6%. Participants experiencing concurrent stress urinary incontinence (SUI) symptoms were more likely to choose a current guideline-approved third-line therapy than ITNS or no therapy at all (p = 0.047). Those who had prior experience with third-line therapies were more likely to choose a third-line therapy other than ITNS as their ultimate choice of therapy in stage B. Of those who had chosen a guideline-approved third-line therapy in stage B (not ITNS), 13.6% had prior experience with BTX-A, 14.7% with PTNS, and 32 (11.2%) with SNM (p < 0.001, p < 0.001, p = 0.009, respectively). CONCLUSION: From our study, it appears that ITNS may attract a subset of patients who would not have otherwise pursued current guideline-approved third-line therapies for OAB. When patients are provided with descriptions of third-line OAB therapies including ITNS as an option, ITNS appears to compete with SNM and PTNS. It is possible that ITNS will provide patients with a different phenotype of neuromodulation therapy that can appeal to a niche OAB population. Given that ITNS devices have been introduced relatively recently to the market, their application will largely depend on cost and payer coverage, provider bias, and patient comorbidities. Further study is needed to understand how these factors interact with and influence patient preference of advanced OAB therapy to understand which patients will most benefit from this treatment modality.

Response to tibial and sacral nerve modulation in overactive bladder: Is there any correlation?

OBJECTIVES: To assess the correlation between the response to transcutaneous tibial nerve stimulation (TTNS) and subsequent response to sacral nerve modulation (SNM) to treat overactive bladder (OAB). MATERIALS AND METHODS: All patients who consecutively received TTNS followed by a two-stage SNM between January 2016 and June 2022 to treat OAB in two university hospital centers were included. The response to each therapy was evaluated with success defined by a 50% or greater improvement in one or more bothersome urinary symptoms from baseline. The primary endpoint was the statistical relationship between the response to TTNS and the response to SNM, assessed by logistic regression. Secondary endpoints were the statistical relationship between the response to TTNS and the response to SNM when controlling for gender, age (<57 years vs. >57 years), presence of an underlying neurological disease, and presence of DO, adding the factor and interaction to the previous regression model. RESULTS: Among the 92 patients enrolled in the study, 68 of them were women (73.9%), and the median age was 57.0 [41.0-69.0] years. The success was reported in 22 patients (23.9%) under TTNS and 66 patients (71.7%) during the SNM test phase. There was no statistical correlation between response to TTNS and response to SNM in the overall population (confidence interval: 95% [0.48-4.47], p = 0.51). Similarly, there was no statistical correlation when controlling for age <57 years or ≥57 years, with p = 1.0 and p = 0.69, respectively. No statistical study could be conducted for the other subpopulations due to small sample sizes. CONCLUSION: The response to TTNS does not predict the response to SNM in the treatment of OAB. TTNS and SNM should be considered as separate therapies, and the decision-making process for OAB treatment should take this into account.

Comparison of tibial nerve pulsed radiofrequency and intralesional radiofrequency thermocoagulation in the treatment of painful calcaneal spur and plantar fasciitis: a randomized clinical trial.

OBJECTIVE: Ultrasound-guided tibial nerve pulsed radiofrequency (US-guided TN PRF) and fluoroscopy-guided intralesional radiofrequency thermocoagulation (FL-guided intralesional RFT) adjacent to the painful calcaneal spur are two interventions for pain management in painful calcaneal spur and plantar fasciitis. This study aimed to compare the effectiveness of the two procedures. DESIGN: A prospective, randomized, single-blind study. SETTING: Single-center pain clinic. SUBJECTS: Forty-nine patients who met the inclusion criteria were randomized into two groups. METHODS: Group U (25 patients) received US-guided TN PRF at 42°C for 240 s, whereas Group F (24 patients) received FL-guided intralesional RFT at 80°C for 90 s. The most severe numeric rating scale (NRS) score during the first morning steps and the American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot scores were used to evaluate the effectiveness of the procedures. The study's primary outcome assessed treatment effectiveness via the NRS, whereas the secondary outcomes included changes in the AOFAS score and the incidence of procedure-related mild adverse events. RESULTS: NRS and AOFAS scores significantly improved in Groups U and F at 1 and 3 months compared with baseline (P < .05), and there was no significant difference between the groups. At month 1, 50% or greater pain relief was achieved in 72% of patients in Group U and 75% of patients in Group F. No significant difference was observed in the incidence of mild adverse events between the groups. CONCLUSIONS: US-guided TN PRF and FL-guided intralesional RFT have shown significant effectiveness in the treatment of painful calcaneal spur and plantar fasciitis. Larger randomized controlled trials are needed. CLINICAL TRIAL NUMBER: NCT06240507.

Effects of Transcutaneous Tibial Nerve Stimulation in Women Refractory to and Never Used Pharmacological Agents for Idiopathic Overactive Bladder.

INTRODUCTION AND HYPOTHESIS: The aim of this study is to compare the effectiveness of transcutaneous tibial nerve stimulation (TTNS) on quality of life (QoL) and clinical parameters related to incontinence in pharmacological agents (PhAs) naive and refractory women with idiopathic overactive bladder (iOAB). METHODS: In this prospective nonrandomized clinical trial, women with resistance to PhAs were included in the first group (n=21), PhA-naive women were included in the second group (n=21). TTNS was performed 2 days a week, a total of 12 sessions for 6 weeks. Every session lasted 30 min. Women were evaluated for the severity of incontinence (Pad test), 3-day voiding diary (voiding frequency, nocturia, incontinence episodes, and number of pads), symptom severity (Overactive Bladder Questionnaire-V8), quality of life (Incontinence Impact Questionnaire-7), treatment satisfaction, positive response, and cure-improvement rates. RESULTS: A statistically significant improvement was found in all parameters for each group at the 6th week compared with the baseline values (p<0.05). It was found that the severity of incontinence, incontinence episodes, symptom severity, treatment satisfaction, and QoL parameters were significantly improved in PhA-naive group compared with the PhA-resistant group at the 6th week (p<0.05). There were no statistically significant differences in the frequency of voiding, nocturia, and number of pads between the two groups (p>0.05). Positive response rates, the primary outcome measure, were statistically significantly higher in the PhA-naive group than in the PhA-resistant group. CONCLUSIONS: Although TTNS is more effective in PhA-naive women with iOAB, it appears to be an effective therapy that can also be used in the management of PhA-resistant women with iOAB.

Posterior Tibial Nerve Stimulation With versus Without Mirabegron: A Randomized Controlled Trial.

INTRODUCTION AND HYPOTHESIS: To compare change in urgency urinary incontinence episodes (UUIEs) in women undergoing posterior tibial nerve stimulation (PTNS) plus mirabegron versus PTNS plus placebo for the treatment of refractory urgency urinary incontinence (UUI). The primary hypothesis was that combination therapy is superior to monotherapy. METHODS: A randomized controlled trial was performed in individuals identifying as female aged ≥ 18 years with UUI symptoms refractory to second-line treatment or who could not tolerate antimuscarinic medications. Both participants and providers were blinded to medication treatment allocation. Participants were randomized (1:1) to PTNS plus mirabegron or PTNS plus placebo. Participants completed a 3-day bladder diary prior to and after 12-week treatment. Validated symptom distress and impact questionnaires were obtained pre- and post-treatment. The primary outcome was change in mean number of UUIEs on a 3-day bladder diary pre- versus post-treatment between arms. Primary and secondary outcomes were analyzed via sample t tests. RESULTS: Fifty-four subjects were randomized, mean ± SD baseline age 56.2±15.6 years and body mass index 35.0±9.4 (kg/m2); no differences were noted in any clinical-demographic characteristics. There was a significant difference between arms in mean pre- to post-treatment UUIEs, 9.4±3.9, mirabegron versus 5.3±5.5, placebo (p=0.007). Significant differences were found pre- compared with post-treatment in urinary frequency, Overactive Bladder Questionnaire Short Form Symptom Bother and Symptom Health-Related Quality of Life scores. CONCLUSIONS: In subjects undergoing PTNS treatment for refractory UUI and OAB-wet symptoms, the addition of a ß-3 agonist produced significant improvement in both objective and subjective overactive bladder symptom outcomes compared with PTNS plus placebo.

Third-Line Therapeutic Interventions for Non-Neurogenic Bladder Dysfunction in Children.

PURPOSE OF REVIEW: The aim of this article is to review considerations and efficacy of third-line treatments for pediatric non-neurogenic bladder dysfunction, including Botulinum toxin A (BoTNA), Posterior Tibial Nerve Stimulation (PTNS), and Sacral Neuromodulation (SNM). RECENT FINDINGS: Federal Drug Administration approval for use of beta-3-agonists in overactive detrusor activity in pediatric patients may provide an additional step prior to third-line therapies. New long-term data on pediatric SNM efficacy, complications, and revision rates will provide valuable information for counseling families. BoTNA offers a safe and efficacious treatment to decrease detrusor contractility and improve bladder capacity but is limited by the half-life of BoNTA agent. Percutaneous or transcutaneous PTNS offers improved voided volumes or cure in some patients but is time-intensive. SNM can be utilized in a variety of LUTD pathology with high success rate and cure but should consider cumulative anesthetic and fluoroscopic exposures for battery replacements and re-positioning for patient growth.

Neuritis ossificans mimicking a malignancy in a child: case report and literature review.

We present the case of a child with neuritis ossificans after acute trauma, treated conservatively. The aim of the review is to compare several parameters in this disease. Emphasis is placed on the clinical-radiological features distinguishing neuritis ossificans from malignancy to avoid unnecessary biopsy and surgery.A literature review was performed. Only 18 cases were described. Except for one, all describe adults, and none had acute trauma. Nearly all were treated surgically.Our 13-year-old patient presented with posterior knee pain after trauma. MRI demonstrated a mass within the tibial nerve with oedema, some lymph nodes and increased avidity on 18fluoro-2-deoxyglucose-positron emission tomography. These findings can be reactive but also associated with malignancy. However, eggshell-like calcifications in the periphery of the mass were seen on CT. Biopsy and resection were proposed. Follow-up visits over the next weeks showed remarkable clinical improvement. Wait-and-scan was advised after international discussion. Follow-up imaging after 2 months showed resolution of the oedema and volume reduction of the mass, suggesting a benign pathology. Diagnosis of neuritis ossificans was proposed based on the clinical and radiological features. There was a favorable course with no complaints after two months. Imaging after seven months showed an almost complete regression.Neuritis ossificans should be considered within a painfull (mono)neuropathy. The initial inflammatory phase may mimic malignancy, misleading clinicians toward biopsy or surgery with the risk of nerve damage. As seen in our case, neuritis ossificans can be a self-limiting process. Therefore, conservative therapy should be considered with a wait-and-scan approach.

Short-term clinical and manometric outcomes of percutaneous tibial nerve stimulation for faecal incontinence: a large single-centre series.

BACKGROUND: Faecal incontinence (FI) is common, with a significant impact on quality of life. Percutaneous tibial nerve stimulation (PTNS) is a therapy for FI; however, its role has recently been questioned. Here we report the short-term clinical and manometric outcomes in a large tertiary centre. METHODS: A retrospective review of a prospective PTNS database was performed, extracting patient-reported FI outcome measures including bowel diary, the St Marks's Incontinence Score (SMIS) and Manchester Health Questionnaire (MHQ). Successful treatment was > 50% improvement in symptoms, whilst a partial response was 25-50% improvement. High-resolution anorectal manometry (HRAM) results before and after PTNS were recorded. RESULTS: Data were available from 135 patients [119 (88%) females; median age: 60 years (range: 27-82years)]. Overall, patients reported a reduction in urge FI (2.5-1) and passive FI episodes (2-1.5; p < 0.05) alongside a reduction in SMIS (16.5-14) and MHQ (517.5-460.0; p < 0.001). Some 76 (56%) patients reported success, whilst a further 20 (15%) reported a partial response. There were statistically significant reductions in rectal balloon thresholds and an increase in incremental squeeze pressure; however, these changes were independent of treatment success. CONCLUSION: Patients report PTNS improves FI symptoms in the short term. Despite this improvement, changes in HRAM parameters were independent of this success. HRAM may be unable to measure the clinical effect of PTNS, or there remains the possibility of a placebo effect. Further work is required to define the role of PTNS in the treatment of FI.

Is percutaneous tibial nerve stimulation (PTNS) effective for fecal incontinence (FI) in adults compared with sham electrical stimulation? A meta-analysis.

BACKGROUND: Sacral nerve neuromodulation (SNM) has been considered the optimal second-line treatment for fecal incontinence (FI). However, SNM involves high cost and requires highly skilled operators. Percutaneous tibial nerve stimulation (PTNS) has emerged as an alternative treatment modality for FI, yielding varying clinical outcomes. We conducted this meta-analysis to evaluate the effectiveness and safety of PTNS compared to sham electrical stimulation for FI. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were searched for studies from May 12, 2012 to May 12, 2022. RESULTS: Four randomized controlled studies were included in this review, involving a total of 439 adult patients with FI (300 in the PTNS group and 194 in the sham electrical stimulation group). Our meta-analysis revealed that PTNS demonstrated superior efficacy in reducing weekly episodes of FI compared to the control groups (MD - 1.6, 95% CI - 2.94 to - 0.26, p = 0.02, I2 = 30%). Furthermore, a greater proportion of patients in the PTNS group reported more than a 50% reduction in FI episodes per week (RR 0.73, 95% CI 0.57-0.94, p = 0.02, I2 = 6%). However, no significant differences were observed in any domains of the FI Quality of Life (QoL) and St Mark's incontinence scores (MD - 2.41, 95% CI - 5.1 to 0.27, p = 0.08, I2 = 67%). Importantly, no severe adverse events related to PTNS were reported in any of the participants. CONCLUSIONS: Our meta-analysis revealed that PTNS was more effective than sham stimulation in reducing FI episodes and led to a higher proportion of patients reporting more than a 50% reduction in weekly FI episodes.

Percutaneous tibial nerve stimulation for the overactive bladder: A single-arm trial.

AIMS: We hypothesise that PTNS is a safe and effective treatment for OAB. Overactive bladder (OAB) is estimated to affect 11.8% of women worldwide, causing diminished quality of life. Lifestyle modifications, muscarinic receptor antagonist and beta-adrenoreceptor agonist remain the mainstay of treatment but are limited by their efficacy and adverse effects. Access to third-line therapies of intravesical botulinum toxin type A or sacral neuromodulation is limited by their invasive nature. Percutaneous tibial nerve stimulation (PTNS) has emerged as a non-invasive treatment option for OAB. METHODS: This study was a single-arm trial of women requesting third-line treatment for OAB. The primary treatment outcome was patient-reported visual analogue score (VAS) improvement of at least 50%. Secondary outcome measures were Urinary Distress Inventory Short Form (UDI-6) score and two-day bladder diary. Patients also provided feedback on adverse effects encountered. RESULTS: In the 84 women recruited, initial treatment protocol showed a success rate of 77.2% among those who completed treatment based on VAS, with a statistically significant improvement in mean UDI-6 score of 20.13 (P < 0.01, standard deviation: 12.52). Continued success following tapering protocol of 60.8% and a mean maintenance protocol of 14.2 months was achieved. No adverse effects were reported. CONCLUSION: The results from this study are in concordance with previously published literature on the effectiveness and safety of PTNS as a treatment modality for OAB. Further randomised controlled trials to evaluate the optimal treatment protocol are warranted to establish a standardised regime.

Immediate and Long-Term Effects of Tibial Nerve Stimulation on the Sexual Behavior of Female Rats.

OBJECTIVES: There are limited treatment options for female sexual dysfunction (FSD). Percutaneous tibial nerve stimulation (PTNS) has shown improvements in FSD symptoms in neuromodulation clinical studies, but the direct effects on sexual function are not understood. This study evaluated the immediate and long-term effects of PTNS on sexual motivation and receptivity in a rat model of menopausal women. Our primary hypothesis was that long-term PTNS would yield greater changes in sexual behavior than short-term stimulation. MATERIALS AND METHODS: In two experiments, after receiving treatment, we placed ovariectomized female rats in an operant chamber in which the female controls access to a male by nose poking. We used five treatment conditions, which were with or without PTNS and no, partial, or full hormone priming. In experiment 1, we rotated rats through each condition twice with behavioral testing immediately following treatment for ten weeks. In experiment 2, we committed rats to one condition for six weeks and tracked sexual behavior over time. We quantified sexual motivation and sexual receptivity with standard measures. RESULTS: No primary comparisons were significant in this study. In experiment 1, we observed increased sexual motivation but not receptivity immediately following PTNS with partial hormone priming, as compared with priming without PTNS (linear mixed effect models; initial latency [p = 0.34], inter-interval latency [p = 0.77], nose poke frequency [p = 0.084]; eight rats). In experiment 2, we observed trends of increased sexual receptivity (linear correlation for weekly group means; mounts [p = 0.094 for trendline], intromissions [p = 0.073], lordosis quotient [p = 0.58], percent time spent with a male [p = 0.39], decreased percent time alone [p = 0.024]; four rats per condition), and some sexual motivation metrics (linear correlation for weekly group means; nose pokes per interval [p = 0.050], nose poke frequency [p = 0.039], decreased initial latency [p = 0.11]; four rats per condition) when PTNS was applied long-term with partial hormone priming, as compared with hormone-primed rats without stimulation. CONCLUSIONS: PTNS combined with hormone priming shows potential for increasing sexual motivation in the short-term and sexual receptivity in the long-term in rats. Further studies are needed to examine variability in rat behavior and to investigate PTNS as a treatment for FSD in menopausal women.

Effects of Posterior Tibial Nerve Stimulation on Fecal Incontinence: An Umbrella Review.

PURPOSE: This study aimed to summarize relevant data from previous systematic reviews (SRs) and conduct comprehensive research on the clinical effects of posterior tibial nerve stimulation (PTNS), via the transcutaneous posterior tibial nerve stimulation (TPTNS) or percutaneous posterior tibial nerve stimulation (PPTNS) method on fecal incontinence (FI). MATERIALS AND METHODS: In adherence to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, a systematic search was conducted on PubMed, Embase, Scopus, and Web of Science databases. We included English-language, full-text SRs reporting outcomes for FI following either PPTNS or TPTNS. The quality of included studies was assessed using the Joanna Briggs Institute checklist. In addition, reanalyzing the meta-analyses was conducted using Comprehensive Meta-Analysis (CMA) software version 3.0 to achieve effect sizes and the level of statistical significance was set at p ≤ 0.05. RESULTS: From a total of 835 citations, 14 SRs met our inclusion criteria. Four of these also conducted a meta-analysis. Most SRs reported an overall improvement in different study parameters, including bowel habits and quality of life. However, there were major inconsistencies across the results. The most studied outcome was FI episodes, followed by incontinence score. The summary outcomes showed no statistically significant changes in comparing PTNS with sham or sacral nerve stimulation (SNS) for FI (p > 0.05). However, the results of subgroup analysis based on the type of intervention in the control group revealed that FI episodes were significantly fewer than in the PTNS arm, whereas PTNS led to fewer episodes of FI than did the sham. In terms of incontinence score, the results showed that PTNS compared with sham did not change the incontinence score; however, SNS improved the score significantly in one eligible study for reanalysis when compared with PTNS (p < 0.001). CONCLUSIONS: The findings of the current umbrella review suggest that PTNS can potentially benefit patients with FI. However, this is concluded from studies with a limited population, disregarding the etiology of FI and with limited follow-up duration. Therefore, caution must be taken in contemplating the results.

Peripheral Nerve Stimulation With a High-Frequency Electromagnetic Coupled Powered Implanted Receiver at the Posterior Tibial Nerve for the Treatment of Chronic Pain in the Foot.

INTRODUCTION: Peripheral neuropathy has several causes, with diabetes being the most common. Conservative management may fail to control pain. Our study aimed at evaluating the use of peripheral nerve stimulation of the posterior tibial nerve for treating peripheral neuropathy. MATERIALS AND METHODS: This was an observational study of 15 patients who received peripheral nerve stimulation at the posterior tibial nerve to treat peripheral neuropathy. Outcomes measured were improvement of pain scores and Patient Global Impression of Change (PGIC) at 12 months compared with before the implant. RESULTS: Mean pain scores with the verbal rating scale were 3 ± 1.8 at >12 months compared with 8.6 ± 1.2 at baseline, a reduction of 65% (p < 0.001). Median satisfaction with the PGIC at >12 months was 7 of 7, with most subjects reporting a 6 (better) or a 7 (a great deal better). CONCLUSION: Peripheral nerve stimulation of the posterior tibial nerve can be a safe and effective modality for treating chronic pain symptoms related to peripheral neuropathy of the foot.

Mechanism of Action of Tibial Nerve Stimulation in the Treatment of Lower Urinary Tract Dysfunction.

BACKGROUND AND OBJECTIVE: Tibial nerve stimulation (TNS) has long been used to effectively treat lower urinary tract dysfunction (LUTD). Although numerous studies have concentrated on TNS, its mechanism of action remains elusive. This review aimed to concentrate on the mechanism of action of TNS against LUTD. MATERIALS AND METHODS: A literature search was performed in PubMed on October 31, 2022. In this study, we introduced the application of TNS for LUTD, summarized different methods used in exploring the mechanism of TNS, and discussed the next direction to investigate the mechanism of TNS. RESULTS AND CONCLUSIONS: In this review, 97 studies, including clinical studies, animal experiments, and reviews, were used. TNS is an effective treatment for LUTD. The study of its mechanisms primarily concentrated on the central nervous system, tibial nerve pathway, receptors, and TNS frequency. More advanced equipment will be used in human experiments to investigate the central mechanism, and diverse animal experiments will be performed to explore the peripheral mechanism and parameters of TNS in the future.

Short-Term Dorsal Genital Nerve Stimulation Increases Subjective Arousal in Women With and Without Spinal Cord Injury: A Preliminary Investigation.

OBJECTIVES: Female sexual dysfunction (FSD) affects an estimated 40% of women. Unfortunately, FSD is understudied, leading to limited treatment options for FSD. Neuromodulation has shown some success in alleviating FSD symptoms. We developed a pilot study to investigate the short-term effect of electrical stimulation of the dorsal genital nerve and tibial nerve on sexual arousal in healthy women, women with FSD, and women with spinal cord injury (SCI) and FSD. MATERIALS AND METHODS: This study comprises a randomized crossover design in three groups: women with SCI, women with non-neurogenic FSD, and women without FSD or SCI. The primary outcome measure was change in vaginal pulse amplitude (VPA) from baseline. Secondary outcome measures were changes in subjective arousal, heart rate, and mean arterial pressure from baseline. Participants attended one or two study sessions where they received either transcutaneous dorsal genital nerve stimulation (DGNS) or tibial nerve stimulation (TNS). At each session, a vaginal photoplethysmography sensor was used to measure VPA. Participants also rated their level of subjective arousal and were asked to report any pelvic sensations. RESULTS: We found that subjective arousal increased significantly from before to after stimulation in DGNS study sessions across all women. TNS had no effect on subjective arousal. There were significant differences in VPA between baseline and stimulation, baseline and recovery, and stimulation and recovery periods among participants, but there were no trends across groups or stimulation type. Two participants with complete SCIs experienced genital sensations. CONCLUSIONS: To our knowledge, this is the first study to measure sexual arousal in response to short-term neuromodulation in women. This study indicates that short-term DGNS but not TNS can increase subjective arousal, but the effect of stimulation on genital arousal is inconclusive. This study provides further support for DGNS as a treatment for FSD.

Low-Intensity Ultrasound Tibial Nerve Stimulation Suppresses Bladder Activity in Rats.

BACKGROUND AND OBJECTIVE: Noninvasive neuromodulation, particularly through low-intensity ultrasound, holds promise in the fields of neuroscience and neuro-engineering. Ultrasound can stimulate the central nervous system to treat neurologic disorders of the brain and activate peripheral nerve activity. The aim of this study is to investigate the inhibitory effect of low-intensity ultrasonic tibial nerve stimulation on both the physiological state and the overactive bladder (OAB) model in rats. MATERIALS AND METHODS: A total of 28 female Sprague-Dawley rats were used in this study. Continuous transurethral instillation of 0.9% normal saline into the bladder was initially performed to stimulate physiological bladder activity. Subsequently, a solution containing 0.3% acetic acid dissolved in saline was instilled to induce rat models of OAB. The study comprised two phases: initial observation of bladder response to low-intensity ultrasound (1 MHz, 1 W/cm2, 50% duty cycle) in seven rats; subsequent exploration of ultrasound frequency (3 MHz) and intensity (2 W/cm2 and 3 W/cm2) effects in 21 rats. The intercontraction intervals (ICIs) were the primary outcome measure. Histologic analysis of tibial nerves and surrounding muscle tissues determined safe ultrasound parameters. RESULTS: Low-intensity ultrasound tibial nerve stimulation significantly inhibited normal and OAB activity. Ultrasound stimulation at 1 MHz, 1 W/cm2, with a 50% duty cycle significantly prolonged the ICI in both normal (p < 0.0001) and OAB rats (p < 0.01), as did transitioning to a 3 MHz frequency (p = 0.001 for normal rats; p < 0.01 for OAB rats). Similarly, at an intensity of 2 W/cm2 and 1 MHz frequency with a 50% duty cycle, ultrasound stimulation significantly prolonged the ICI in both normal (p < 0.01) and OAB rats (p < 0.005). Furthermore, switching to a 3 W/cm2 ultrasound intensity also significantly extended the ICI in both normal (p < 0.05) and OAB rats (p = 0.01). However, after different ultrasound intensities and frequencies, there was no statistical difference in ICI ratios (preultrasound stimulation vs postultrasound stimulation/preultrasound stimulation ∗ 100%) in all rats (p > 0.05). Low-intensity ultrasound tibial nerve stimulation did not influence baseline pressure, threshold pressure, or maximum pressure. In addition, a latency period in bladder reflex inhibition was induced by low-intensity ultrasound tibial nerve stimulation in some rats. Histologic analysis indicated no evident nerve or muscle tissue damage or abnormalities. CONCLUSIONS: This study confirmed the potential of transcutaneous ultrasound tibial nerve stimulation to improve bladder function. According to the findings, the ultrasonic intensities ranging from 1 to 3 W/cm2 and frequencies of 1 MHz and 3 MHz are both feasible and safe treatment parameters. This study portended the promise of low-intensity ultrasound tibial nerve stimulation as a treatment for OAB and provides a basis and reference for future clinical applications.