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Percutaneous tibial nerve stimulation (PTNS) is a new ambulatory therapy for faecal incontinence. Data from case series suggest it has beneficial outcomes in 50–80% patients; however its effectiveness against sham electrical stimulation has not been investigated. We therefore aimed to assess the short-term efficacy of PTNS against sham electrical stimulation in adults with faecal incontinence. We did a double-blind, multicentre, pragmatic, parallel-group, randomised controlled trial (CONtrol of Faecal Incontinence using Distal NeuromodulaTion [CONFIDeNT]) in 17 specialist hospital units in the UK that had the skills to manage patients with faecal incontinence. Eligible participants aged 18 years or older with substantial faecal incontinence for whom conservative treatments (such as dietary changes and pelvic floor exercises) had not worked, were randomly assigned (1:1) to receive either PTNS (via the Urgent PC neuromodulation system) or sham stimulation (via a transcutaneous electrical nerve stimulation machine to the lateral forefoot) once per week for 12 weeks. Randomisation was done with permuted block sizes of two, four, and six, and was stratified by sex and then by centre for women. Patients and outcome assessors were both masked to treatment allocation for the 14-week duration of the trial (but investigators giving the treatment were not masked). The primary outcome was a clinical response to treatment, which we defined as a 50% or greater reduction in episodes of faecal incontinence per week. We assessed this outcome after 12 treatment sessions, using data from patients' bowel diaries. Analysis was by intention to treat, and missing data were multiply imputed. This trial is registered with the ISRCTN registry, number 88559475, and is closed to new participants. Between Jan 23, 2012, and Oct 31, 2013, we randomly assigned 227 eligible patients (of 373 screened) to receive either PTNS (n=115) or sham stimulation (n=112). 12 patients withdrew from the trial: seven from the PTNS group and five from the sham group (mainly because they could not commit to receiving treatment every week). Two patients (one in each group) withdrew because of an adverse event that was unrelated to treatment (exacerbation of fibromyalgia and rectal bleeding). 39 (38%) of 103 patients with full data from bowel diaries in the PTNS group had a 50% or greater reduction in the number of episodes of faecal incontinence per week compared with 32 (31%) of 102 patients in the sham group (adjusted odds ratio 1·28, 95% CI 0·72–2·28; p=0·396). No serious adverse events related to treatment were reported in the trial. Seven mild, related adverse events were reported in each treatment group, mainly pain at the needle site (four in PTNS, three in sham). PTNS given for 12 weeks did not confer significant clinical benefit over sham electrical stimulation in the treatment of adults with faecal incontinence. Further studies are warranted to determine its efficacy in the long term, and in patient subgroups (ie, those with urgency). National Institute for Health Research.

Background Friedreich's ataxia (FRDA) affects both the central and peripheral nervous system. Peripheral nerve involvement manifests predominantly as a progressive sensory neuropathy caused by dorsal root ganglionopathy. An additional direct involvement of peripheral nerves leading to abnormal myelination is increasingly discussed. Here, we characterize lower extremity peripheral nerve involvement in FRDA by quantitative magnetic resonance neurography (MRN). Methods Sixteen genetically confirmed FRDA patients and 16 age‐/sex‐matched controls were prospectively enrolled. Patients underwent neurologic examinations and nerve conduction studies (NCS). Large‐coverage MRN of sciatic and tibial nerves was conducted utilizing dual‐echo turbo‐spin‐echo sequences with spectral fat saturation for T2‐relaxometry, and two gradient‐echo sequences with and without off‐resonance saturation rapid frequency pulses for magnetization transfer contrast imaging. Microstructural and morphometric MRN markers including T2‐relaxation time (T2app), proton spin density (ρ), magnetization transfer ratio (MTR), and cross‐sectional area (CSA) were calculated to characterize nerve lesions. Results Tibial nerve ρ and T2app were markedly decreased in FRDA at the thigh (ρ: 368.4 ± 11.0 a.u.; T2app: 59.5 ± 1.8 ms) and lower leg (ρ: 337.3 ± 12.6 a.u.; T2app: 53.9 ± 1.4 ms) versus controls (thigh, ρ: 458.9 ± 9.5 a.u., p < 0.0001; T2app: 66.3 ± 0.8 ms, p = 0.0019; lower leg, ρ: 449.9 ± 12.1 a.u., p < 0.0001; T2app: 62.4 ± 1.2 ms, p < 0.0001) and correlated well with clinical scores, disease duration, and NCS. MTR and CSA did not differentiate between FRDA and controls. Conclusion Our study results provide a profound characterization of peripheral nerve involvement in FRDA. The identified good correlation between ρ and T2app with clinical symptom scores and NCS suggests that parameters of T2 relaxometry may become relevant biomarkers to monitor disease progression and therapeutic responses in potential future clinical trials.

Surgical reapposition of peripheral nerve results in some axonal regeneration and functional recovery, but the clinical outcome in long distance nerve defects is disappointing and research continues to utilize further interventional approaches to optimize functional recovery. We describe the use of nerve constructs consisting of decellularized vein grafts filled with spider silk fibers as a guiding material to bridge a 6.0 cm tibial nerve defect in adult sheep. The nerve constructs were compared to autologous nerve grafts. Regeneration was evaluated for clinical, electrophysiological and histological outcome. Electrophysiological recordings were obtained at 6 months and 10 months post surgery in each group. Ten months later, the nerves were removed and prepared for immunostaining, electrophysiological and electron microscopy. Immunostaining for sodium channel (NaV 1.6) was used to define nodes of Ranvier on regenerated axons in combination with anti-S100 and neurofilament. Anti-S100 was used to identify Schwann cells. Axons regenerated through the constructs and were myelinated indicating migration of Schwann cells into the constructs. Nodes of Ranvier between myelin segments were observed and identified by intense sodium channel (NaV 1.6) staining on the regenerated axons. There was no significant difference in electrophysiological results between control autologous experimental and construct implantation indicating that our construct are an effective alternative to autologous nerve transplantation. This study demonstrates that spider silk enhances Schwann cell migration, axonal regrowth and remyelination including electrophysiological recovery in a long-distance peripheral nerve gap model resulting in functional recovery. This improvement in nerve regeneration could have significant clinical implications for reconstructive nerve surgery.

The management of childhood constipation is challenging. Pelvic floor dysfunction (PFD) is one of the most common causes of childhood constipation. Percutaneous tibial nerve stimulation (PTNS) with pelvic floor exercises (PFE) has achieved a satisfactory outcome in the elderly individuals and women with PFD. The efficacy of PTNS with PFE in childhood constipation has not been established. A randomized, double-blind, controlled trial with 84 children who met the inclusion criteria was conducted. All participants were randomly assigned to PTNS with PFE or sham PTNS with PFE groups and received their individual intervention for 4 weeks with a 12-week follow-up evaluation. The spontaneous bowel movements (SBM) ≥3 per week were the main outcomes, and the risk ratio (RR) with 95% confidence interval (CI) were calculated. High-resolution anorectal manometry and surface electromyography were used for the assessment of pelvic floor function, and the adverse effects were assessed based on symptoms. At the end of the follow-up period, 26 patients (61.9%) in the PTNS with PFE group and 15 patients (35.7%) in the sham group had ≥3 SBM per week compared with baseline (net difference 26.2%, 95% CI 5.6%-46.8%; RR 2.750, 95% CI 1.384-5.466; P < 0.05). PFD remission occurred in 49 children, 33 (78.6%) in the PTNS with PFE group and 16 (38.1%) in the sham group (RR 2.063, 95% CI 1.360-3.128, P < 0.05). No adverse effects occurred. PTNS with PFE is a safe and effective method in the treatment of childhood constipation, particularly in children with PFD or dyssynergic defecation.

To determine whether percutaneous tibial nerve stimulation (PTNS) is superior to sham stimulation for the treatment of fecal incontinence (FI) in women refractory to first-line treatments. Women aged 18 years or older with ≥3 months of moderate-to-severe FI that persisted after a 4-week run-in phase were randomized 2:1 (PTNS:sham stimulation) to 12 weekly 30-minute sessions in this multicenter, single-masked, controlled superiority trial. The primary outcome was change from baseline FI severity measured by St. Mark score after 12 weeks of treatment (range 0-24; minimal important difference, 3-5 points). The secondary outcomes included electronic bowel diary events and quality of life. The groups were compared using an adjusted general linear mixed model. Of 199 women who entered the run-in period, 166 (of 170 eligible) were randomized, (111 in PTNS group and 55 in sham group); the mean (SD) age was 63.6 (11.6) years; baseline St. Mark score was 17.4 (2.7); and recording was 6.6 (5.5) FI episodes per week. There was no difference in improvement from baseline in St. Mark scores in the PTNS group when compared with the sham group (-5.3 vs -3.9 points, adjusted difference [95% confidence interval] -1.3 [-2.8 to 0.2]). The groups did not differ in reduction in weekly FI episodes (-2.1 vs -1.9 episodes, adjusted difference [95% confidence interval] -0.26 [-1.85 to 1.33]). Condition-specific quality of life measures did not indicate a benefit of PTNS over sham stimulation. Serious adverse events occurred in 4% of each group. Although symptom reduction after 12 weeks of PTNS met a threshold of clinical importance, it did not differ from sham stimulation. These data do not support the use of PTNS as conducted for the treatment of FI in women.

Introduction and hypothesis In randomized trials both percutaneous tibial nerve stimulation (PTNS) and sham result in clinically significant improvements in accidental bowel leakage (ABL). We aimed to identify subgroups who may preferentially benefit from PTNS in women enrolled in a multicenter randomized trial. Methods This planned secondary analysis explored factors associated with success for PTNS vs sham using various definitions: treatment responder using three cutoff points for St. Mark’s score (≥3-, ≥4-, and ≥5-point reduction); Patient Global Impression of Improvement (PGI-I) of ≥ much better; and ≥50% reduction in fecal incontinence episodes (FIEs). Backward logistic regression models were generated using elements with significance of p <0.2 for each definition and interaction terms assessed differential effects of PTNS vs sham. Results Of 166 women randomized, 160 provided data for at least one success definition. Overall, success rates were 65% (102 out of 158), 57% (90 out of 158), and 46% (73 out of 158) for ≥3-, ≥4-, and ≥5-point St Mark’s reduction respectively; 43% (68 out of 157) for PGI-I; and 48% (70 out of 145) for ≥50% FIEs. Of those providing data for all definitions of success, 77% (109 out of 142) met one success criterion, 43% (61 out of 142) two, and 29% (41 out of 142) all three success criteria. No reliable or consistent factors were associated with improved outcomes with PTNS over sham regardless of definition. Conclusions Despite exploring diverse success outcomes, no subgroups of women with ABL differentially responded to PTNS over sham. Success results varied widely across subjective and objective definitions. Further investigation of ABL treatment success definitions that consistently and accurately capture patient symptom burden and improvement are needed.

Purpose. Although many surgeons have anecdotally described reversing the polarity of the autograft with the intent of improving regeneration, the optimal orientation of the autogenous nerve graft remains controversial. The aim of this study was to compare (1) the outcomes of orthodromic and antidromic nerve grafts to clarify the effect of nerve graft polarity and (2) the outcome of either form of nerve grafts with that of nerve repair. Methods. In 14 of the 26 rabbits used in this study, a 1 cm defect was made in the tibial nerve. An orthodromic nerve graft on one side and an antidromic nerve graft on the other were performed using a 1.2 cm long segment of the peroneal nerve. In the remaining 12 rabbits, the tibial nerve was transected completely and then repaired microscopically on one side but left untreated on the other. Electrophysiologic studies were performed in all animals at 8 weeks after surgery, and the sciatic nerves were harvested. Results. Compound motor action potential was visible in all rabbits treated by nerve repair but in only half of the rabbits treated by nerve graft. There was no significant difference in the compound motor action potential, nerve conduction velocity, or total number of axons between the orthodromic and antidromic nerve graft groups. However, in both groups, the outcome was significantly poorer than that of the nerve repair group. Conclusion. There was no significant difference by electromyographic or histologic evaluation between orthodromic and antidromic nerve grafts. Direct nerve repair with moderate tension may be a more effective treatment than nerve grafting.

Most children with functional constipation (FC) improve with conventional treatments. However, a proportion of children have poor treatment outcomes. Management of intractable FC may include botulinum toxin injections, transanal irrigation, antegrade enemas, colonic resections, and in some cases sacral nerve stimulation (SNS). SNS is surgically placed, not readily available and expensive. Posterior tibial nerve stimulation (PTNS) allows transmission of electronic impulses and retrograde stimulation to the sacral nerve plexus in a portable, simple and non-invasive fashion. To assess the efficacy and safety of transcutaneous PTNS for the treatment of FC in children. Single-center, prospective interventional study. Children 4–14 years with Rome IV diagnosis of FC received ten daily PTNS (30 min/day) sessions. Electrodes placed over skin of ankle. Strength of stimulus was below pain threshold. Outcomes were assessed during treatment and 7 days after. Twenty-three subjects enrolled. Two children excluded (acute gastroenteritis, COVID-19 contact). Twenty completed the study (4–14 years), (8.4 ± 3.2 years, 71.4% female). We found significant improvement in the consistency of bowel movements (BM) ( p  = 0.005), fecal incontinence (FI) ( p  = 0.005), abdominal pain presence ( p  = < 0.001) and intensity ( p  = 0.005), and a significant for improvement in blood in stools ( p  = 0.037). There was 86.3% improvement in abdominal pain. 96.7% reported treatment satisfaction. Only one child required rescue therapy. Conclusion: We found significant improvement in stool consistency, FI, abdominal pain, and hematochezia. This suggests that transcutaneous PTNS could be a promising noninvasive treatment for FC in children. Large studies are needed. What is Known: • Functional constipation is one of the most common disorders in children. • Current management of functional constipation consists of an integrative approach that includes medications, diet and behavioral strategies. What is New: • Posterior tibial nerve stimulation is a novel noninvasive and easy to use therapy that can improve stool consistency, fecal incontinence and blood in stools.

Objectives To evaluate the efficacy and safety of a non-invasive low-frequency tibial nerve stimulator (TNS-01) vs sham control in relieving the symptoms of overactive bladder (OAB) patients. Patients Participants who were diagnosed with primary OAB or exhibited at least one OAB symptom. All participants underwent three 30-min intervention sessions weekly. Methods The subjects were 1:1randomized (block randomization with a block size of 4) to either active treatment (TNS-01 group) or sham treatment (sham group). Based on the randomization, the subject will be given either an active or sham device system (systems will only differ in the Instructions for Use and electrode size/shape). During the 12-week study period, all participants underwent three 30-min intervention sessions weekly. The primary endpoint was the change in Overactive Bladder Symptom Score (OABSS) at week 12 from the baseline. Results Of the 109 recruited OAB patients. In the TNS-01 group, the OABSS change from baseline at week 12 was significantly higher than that in the sham group (2.83 ± 2.53 vs 1.62 ± 2.59, p  = 0.02). The absolute and percent changes of average UUI episodes per day from baseline at week 8 in the TNS-01 group were significantly lower from those in the sham group (0.11 ± 1.33 vs 0.68 ± 2.14, p  = 0.01; − 27.82% ± 167.33% vs 87.18% ± 25.20%, p  = 0.04). One treatment-related adverse event (hematuria) was reported by one patient (1.8%) in the sham group. Conclusions The TNS-01 device is effective and safe in relieving OAB symptoms after 12 weeks of stimulation. Trial registration number: NCT04999657.

Background Overactive bladder syndrome is common, with a prevalence of 12–17% among adults. Posterior tibial nerve stimulation is the primary nonpharmacological and conservative treatment for overactive bladder syndrome. While several human brain imaging studies have shown the involvement of supraspinal centers in bladder control, a literature review has found that no research has specifically investigated cortical stimulation through transcranial direct current stimulation as a treatment for overactive bladder syndrome in women. Therefore, this study aims to assess the potential benefits of transcranial direct current stimulation (tDCS) and compare them with the effects of posterior tibial nerve stimulation on overactive bladder syndrome. Methods/design The random allocation method will be used to divide the participants into two groups. Group 1 ( n  = 19) will undergo pelvic floor muscle training and transcutaneous tibial nerve stimulation. Group 2 ( n  = 19) will undergo pelvic floor muscle training and transcranial direct current stimulation. The transcranial direct current stimulation for group 2 will consist of 12 sessions occurring thrice a week, each lasting for 20 min. Anodal tDCS will be administered to FPz targeting the medial prefrontal cortex (mPFC) for 12 sessions, with the cathode electrode positioned between Oz and inion at an intensity of 2 mA for 20 min. Discussion It is believed that utilizing an approach involving non-invasive electrical stimulation of the cortex could lead to a more efficient treatment for individuals with overactive bladder. Additionally, it is theorized that combining the effects of tDCS and pelvic floor muscle training could present an innovative technique for alleviating the negative impacts of overactive bladder syndrome. Ultimately, this new method could provide help for patients who have not responded to conventional therapy. Trial registration Iranian Registry of Clinical Trials (IRCT) ID: IRCT20090301001722N26, registration date: May 17, 2023. https://en.irct.ir/ .