Brain Response Induced by Peroneal Electrical Transcutaneous Neuromodulation Invented for Overactive Bladder Treatment, as Detected by Functional Magnetic Resonance Imaging.

OBJECTIVES: In this study, we aimed to investigate whether peroneal electrical Transcutaneous Neuromodulation invented for overactive bladder (OAB) treatment elicits activation in brain regions involved in neural regulation of the lower urinary tract. MATERIALS AND METHODS: Among 22 enrolled healthy female volunteers, 13 were eligible for the final analysis. Functional magnetic resonance imaging (fMRI) (Siemens VIDA 3T; Erlangen, Germany) was used to compare the brain region activation elicited by peroneal electrical Transcutaneous Neuromodulation with the activation elicited by sham stimulation. Each subject underwent brain fMRI recording during eight 30-second periods of rest, alternating with 30-second periods of passive feet movement using the sham device, mimicking the motor response to peroneal nerve stimulation. Subsequently, fMRI recording was performed during the analogic "off-on" stimulation paradigm using peroneal electrical transcutaneous neuromodulation. Magnetic resonance imaging data acquired during both paradigms were compared using individual and group statistics. RESULTS: During both peroneal electrical Transcutaneous Neuromodulation and sham feet movements, we observed activation of the primary motor cortex and supplementary motor area, corresponding to the cortical projection of lower limb movement. During peroneal electrical Transcutaneous Neuromodulation, we observed significant activations in the brain stem, cerebellum, cingulate gyrus, putamen, operculum, and anterior insula, which were not observed during the sham feet movement. CONCLUSIONS: Our study provides evidence that peroneal electrical Transcutaneous Neuromodulation elicits activation of brain structures that have been previously implicated in the perception of bladder fullness and that play a role in the ability to cope with urinary urgency. Our data suggest that neuromodulation at the level of supraspinal control of the lower urinary tract may contribute to the treatment effect of peroneal electrical Transcutaneous Neuromodulation in patients with OAB.

Transcutaneous Electrical Stimulation of the Abdomen, Ear, and Tibial Nerve Modulates Bladder Contraction in a Rat Detrusor Overactivity Model: A Pilot Study.

PURPOSE: The global prevalence of overactive bladder (OAB) is estimated at 11.8%. Despite existing treatment options such as sacral neuromodulation, a substantial number of patients remain untreated. One potential alternative is noninvasive transcutaneous electrical stimulation. This form of stimulation does not necessitate the implantation of an electrode, thereby eliminating the need for highly skilled surgeons, expensive implantable devices, or regular hospital visits. We hypothesized that alternative neural pathways can impact bladder contraction. METHODS: In this pilot study, we conducted transcutaneous electrical stimulation of the abdominal wall (T6-L1), the ear (vagus nerve), and the ankle (tibial nerve) of 3 anesthetized female Sprague-Dawley rats. Stimulation was administered within a range of 20 Hz to 20 kHz, and its impact on intravesical pressure was measured. We focused on 3 primary outcomes related to intravesical pressure: (1) the pressure change from the onset of a contraction to its peak, (2) the average duration of contraction, and (3) the number of contractions within a specified timeframe. These measurements were taken while the bladder was filled with either saline or acetic acid (serving as a model for OAB). RESULTS: Transcutaneous stimulation of the abdominal wall, ear, and ankle at a frequency of 20 Hz decreased the number of bladder contractions during infusion with acetic acid. As revealed by a comparison of various stimulation frequencies of the tibial nerve during bladder infusion with acetic acid, the duration of contraction was significantly shorter during stimulation at 1 kHz and 3 kHz relative to stimulation at 20 Hz (P = 0.025 and P = 0.044, respectively). CONCLUSION: The application of transcutaneous electrical stimulation to the abdominal wall, ear, and tibial nerve could provide less invasive and more cost-effective treatment options for OAB relative to percutaneous tibial nerve stimulation and sacral neuromodulation. A follow-up study involving a larger sample size is recommended.

Differences between brain responses to peroneal electrical transcutaneous neuromodulation and transcutaneous tibial nerve stimulation, two treatments for overactive bladder.

OBJECTIVES: To compare brain responses to peroneal electrical transcutaneous neuromodulation (peroneal eTNM®) and transcutaneous tibial nerve stimulation (TTNS), two methods for treating overactive bladder (OAB), using functional magnetic resonance imaging (fMRI). The present study was not designed to compare their clinical efficacy. MATERIALS AND METHODS: This study included 32 healthy adult female volunteers (average age 38.3 years (range 22-73)). Brain MRI using 3 T scanner was performed during three 8-min blocks of alternating sequences. During each 8-min block, the protocol alternated between sham stimulation (30 s) and rest (30 s) for 8 repeats; then peroneal eTNM® stimulation (30 s) and rest (30 s) for 8 repeats; then, TTNS stimulation (30 s) and rest (30 s) for 8 repeats. Statistical analysis was performed at the individual level with a threshold of p = 0.05, family-wise error (FWE)-corrected. The resulting individual statistical maps were analyzed in group statistics using a one-sample t-test, p = 0.05 threshold, false discovery rate (FDR)-corrected. RESULTS: During peroneal eTNM®, TTNS, and sham stimulations, we recorded activation in the brainstem, bilateral posterior insula, bilateral precentral gyrus, bilateral postcentral gyrus, left transverse temporal gyrus, and right supramarginal gyrus. During both peroneal eTNM® and TTNS stimulations, but not sham stimulations, we recorded activation in the left cerebellum, right transverse temporal gyrus, right middle frontal gyrus, and right inferior frontal gyrus. Exclusively during peroneal eTNM® stimulation, we observed activation in the right cerebellum, right thalamus, bilateral basal ganglia, bilateral cingulate gyrus, right anterior insula, right central operculum, bilateral supplementary motor cortex, bilateral superior temporal gyrus, and left inferior frontal gyrus. CONCLUSIONS: Peroneal eTNM®, but not TTNS, induces the activation of brain structures that were previously implicated in neural control of the of bladder filling and play an important role in the ability to cope with urgency. The therapeutic effect of peroneal eTNM® could be exerted, at least in part, at the supraspinal level of neural control.

Effect duration of the initial course of peroneal electrical Transcutaneous NeuroModulation in patients with overactive bladder.

PURPOSE: The aim of this prospective 12-month follow-up study is to evaluate the persistence of the treatment effect achieved during the initial course of peroneal electrical Transcutaneous NeuroModulation (peroneal eTNM®) in patients with overactive bladder (OAB). METHODS: This study enrolled 21 female patients who participated in two previous clinical studies designed to assess the efficacy and safety of peroneal eTNM®. The patients were left without subsequent OAB treatment and were invited to attend regular follow-up visits every 3 months. The patient's request for additional treatment was considered an indicator of the withdrawal of the treatment effect of the initial course of peroneal eTNM®. The primary objective was the proportion of patients with persisting treatment effect at follow-up visit 12 months after initial course of peroneal eTNM®. Descriptive statistics are presented using median, correlation analyses were computed using a nonparametric Spearman correlation. RESULTS: The proportion of patients with persistent therapeutic effect of the initial course of peroneal eTNM® was 76%, 76%, 62% and 48% at 3, 6, 9 and 12 months, respectively. There was a significant correlation between patient reported outcomes and the number of severe urgency episodes with or without urgency incontinence as reported by patients at each follow-up visit (p = 0.0017). CONCLUSION: The treatment effect achieved during the initial phase of peroneal eTNM® persists for at least 12 months in 48% of patients. It is likely that the duration of effects is dependent on the length of the initial therapy.

Androgen receptors in the forebrain: A study in adult male cats.

Androgens and their receptors are present throughout the body. Various structures such as muscles, genitals, and prostate express androgen receptors. The central nervous system also expresses androgen receptors. Androgens cross the blood-brain barrier to reach these central areas. In the central nervous system, androgens are involved in multiple functions. The current study investigated in which forebrain areas androgens are expressed in the male cat. Androgen receptor immunoreactive (AR-IR) nuclei were plotted and the results were quantified with a Heidelberg Topaz II + scanner and Linocolor 5.0 software. The density and intensity of the labeled cells were the main outcomes of interest. The analysis revealed a dense distribution of AR-IR nuclei in the preoptic area, periventricular complex of the hypothalamus, posterior hypothalamic area, ventromedial hypothalamic, parvocellular hypothalamic, infundibular, and supramammillary nucleus. Numerous AR-IR cells were also observed in the dorsal division of the anterior olfactory nucleus, lateral septal nucleus, medial and lateral divisions of the bed nucleus of the stria terminalis, lateral olfactory tract nucleus, anterior amygdaloid area, and the central and medial amygdaloid nuclei. AR-IR nuclei were predominantly observed in areas involved in autonomic and neuroendocrinergic responses which are important for many physiological processes and behaviors.

Two-Staged Sacral Neuromodulation for the Treatment of Nonobstructive Urinary Retention: A Multicenter Study Assessing Predictors of Success.

OBJECTIVES: The aims of this study were to 1) determine the success rate of the tined lead test phase in patients with nonobstructive urinary retention (NOUR), 2) determine predictive factors of a successful test phase in patients with NOUR, and 3) determine long-term treatment efficacy and satisfaction in patients with NOUR. MATERIALS AND METHODS: The first part was a multicenter retrospective study at two centers in The Netherlands. Patients with NOUR received a four-week tined lead test phase. Success was defined as a ≥50% reduction of clean intermittent catheterization frequency or postvoid residual. We analyzed possible predictors of success with multivariable logistic regression. Second, all patients received a questionnaire to assess efficacy, perceived health (Patient Global Impression of Improvement), and treatment satisfaction. RESULTS: This study included 215 consecutive patients (82 men and 133 women) who underwent a tined lead test phase for the treatment of NOUR. The success rate in women was significantly higher than in men, respectively 62% (83/133) and 22% (18/82, p < 0.001). In women, age per ten years (odds ratio [OR] 0.74, 95% CI: 0.59-0.93) and a history of psychiatric illness (OR 3.92, 95% CI: 1.51-10.2), including posttraumatic stress disorder (PTSD), significantly predicted first stage sacral neuromodulation (SNM) success. In men, age per ten years (OR 0.43, 95% CI: 0.25-0.72) and previous transurethral resection of the prostate and/or bladder neck incision (OR 7.71, 95% CI: 1.43-41.5) were significant predictors of success. Conversely, inability to void during a urodynamic study (for women, OR 0.79, 95% CI: 0.35-1.78; for men, OR 3.06, 95% CI: 0.83-11.3) was not predictive of success. Of the patients with a successful first stage, 75% (76/101) responded to the questionnaire at a median follow-up of three years. Of these patients, 87% (66/76) continued to use their SNM system, and 92% (70/76) would recommend SNM to other patients. CONCLUSIONS: A history of psychiatric illness, including PTSD, in women with NOUR increased the odds of first stage SNM success 3.92 times. A previous transurethral resection of the prostate and/or bladder neck incision in men increased the odds of success 7.71 times. In addition, a ten-year age increase was associated with an OR of 0.43 in men and 0.74 in women, indicating a 2.3- and 1.3-times decreased odds of success, respectively.

Prospective, Randomized, Multicenter Trial of Peroneal Electrical Transcutaneous Neuromodulation vs Solifenacin in Treatment-naïve Patients With Overactive Bladder.

PURPOSE: We investigated the safety and efficacy of peroneal electrical transcutaneous neuromodulation using the URIS neuromodulation system in a home-based setting in comparison with standard treatment using solifenacin in treatment-naïve female patients with overactive bladder. MATERIALS AND METHODS: A total of 120 patients were screened, of whom 77 were randomized in a 2:1 ratio to 12 weeks of treatment with daily peroneal electrical transcutaneous neuromodulation or solifenacin 5 mg. The primary endpoint was safety; efficacy assessments included proportion of responders, defined as subjects with ≥50% reduction in bladder diary-derived variables; Overactive Bladder-Validated 8-question Screener, and European Quality of Life-5 Dimensions questionnaire; and treatment satisfaction after 12 weeks of therapy. RESULTS: Seventy-one out of 77 randomized patients completed the study. In the peroneal electrical transcutaneous neuromodulation group 6/51 (12%) patients reported a treatment-related adverse event vs 12/25 (48%) in the solifenacin group (P < .001). No clinically significant changes were observed in any other safety endpoint. The proportions of responders in the peroneal electrical transcutaneous neuromodulation group vs the solifenacin group were 87% vs 74% with respect to Patient Perception of Intensity of Urgency Scale grade 3 urgency episodes, 87% vs 75% with respect to grade 3+4 urgency episodes, and 90% vs 94% with respect to urgency incontinence episodes. In post hoc analyses we observed significant improvement over time in multiple efficacy variables in both treatment arms. CONCLUSIONS: Peroneal electrical transcutaneous neuromodulation is a safe and effective method for overactive bladder treatment associated with a significantly lower incidence of treatment-related adverse events compared to solifenacin and a considerably better benefit-risk profile.

Transcutaneous Electrical Nerve Stimulation and Percutaneous Tibial Nerve Stimulation to Treat Idiopathic Nonobstructive Urinary Retention: A Systematic Review.

CONTEXT: Transcutaneous electrical nerve stimulation (TENS) and percutaneous tibial nerve stimulation (PTNS) provide minimally invasive ways to treat idiopathic nonobstructive urinary retention (NOUR). OBJECTIVE: To assess the efficacy of TENS and PTNS for treating idiopathic NOUR. EVIDENCE ACQUISITION: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Embase, Medline, Web of Science Core Collection, and the Cochrane CENTRAL register of trials were searched for all relevant publications until April 2020. EVIDENCE SYNTHESIS: A total of 3307 records were screened based on the title and abstract. Eight studies met the inclusion criteria and none of the exclusion criteria. Five studies, all from the same group, reported the efficacy of PTNS and two that of TENS in adults with idiopathic NOUR. One study reported the efficacy of TENS in children with idiopathic NOUR. Objective success was defined as a ≥50% decrease in the number of catheterizations per 24 h or in the total catheterized volume in 24 h. The objective success rate of PTNS ranged from 25% to 41%. Subjective success was defined as the patient's request for continued chronic treatment with PTNS, and ranged from 46.7% to 59%. Eighty percent of women who underwent transvaginal stimulation reported an improvement such as a stronger stream when voiding. TENS in children reduced postvoid residual and urinary tract infections. CONCLUSIONS: The efficacy of TENS and PTNS in the treatment of idiopathic NOUR is limited and should be verified in larger randomized studies before application in clinical practice. PATIENT SUMMARY: The outcomes of transcutaneous electrical nerve stimulation and percutaneous tibial nerve stimulation for the treatment of urinary retention of unknown origin were reviewed. Whether these treatments are superior to other treatments could not be established.

Acute effect of sacral neuromodulation for treatment of detrusor overactivity on urodynamic parameters.

AIM: The aim of this study is to evaluate the acute effects of sacral neuromodulation (SNM) on various urodynamic parameters. METHODS: Patients with overactive bladder and detrusor overactivity (DO) who were planned for percutaneous nerve evaluation (PNE) were included. Directly after the PNE, a urodynamic study (UDS) was performed. The stimulation was turned off during the first UDS (UDS 1), and during the second filling cycle, stimulation was turned on (UDS 2). The UDS was followed by a test phase of 1 week and the bladder diaries were evaluated during an outpatient clinic visit. Primary outcome measures were the differences in UDS parameter values with SNM off and on. RESULTS: Ten female patients were included in the study and completed the study protocol. Eight patients showed ≥50% improvement of symptoms following a test phase. There were no differences between UDS 1 and UDS 2 in the UDS parameters; bladder volume at first sensation, bladder volume at first DO, highest DO pressure, bladder capacity, maximum flow rate, and pressure at maximum flow rate. DISCUSSION: None of the aforementioned urodynamic parameters was influenced by acute SNM in patients who responded to SNM. To the best of our knowledge, this is the first study investigating the acute effects of SNM on bladder function.

Outcome and complications of adjustable continence therapy (ProACTTM ) in the treatment of urinary incontinence after transurethral resection of the prostate: A multicenter study.

AIM: To evaluate the outcome of adjustable continence balloons in the treatment of stress urinary incontinence (SUI) after transurethral resection of the prostate (TURP). METHODS: In two tertiary centers, adjustable continence balloons were implanted in 29 patients with post-TURP SUI between 2007 and 2018. Endpoints of this retrospective multicenter study were patient-reported changes in pad count and complications. Dry was defined as no pad or one security pad. RESULTS: Preoperative urinary incontinence was mild in 7 (24%), moderate in 12 (41%), and severe in 10 (35%) patients. The median follow-up duration was 21 (interquartile range [IQR], 11-43) months. Within 30 days postoperatively, a Clavien-Dindo grade less than or equal to II complication occurred in 24% of the patients. Reintervention rate was 24%. Six and 12 months after implantation, the International Prostate Symptom Score (IPSS) quality-of-life item improved significantly from 5 (IQR, 5-6) preoperatively to 3 (IQR, 1-4.5) and 1 (IQR, 0-3), respectively. At last visit (median 21 months after implantation), the outcome on continence had improved in 76% of the patients, including, 45% dry patients. After a median follow-up of 28 months (IQR, 13-63; N = 23), all but one patient reported improvement on the Patient Global Impression of Improvement (PGI-I) scale. In detail, 10 patients reported "very much better" condition compared with before the implantation, 10 patients "much better," two patients "a little better," and one patient "no change." Daily pad use decreased from three (IQR, 2-5) to one (IQR, 0-2) pads/day (P < 0.001). CONCLUSIONS: This is hitherto, the first study reporting results of adjustable continence balloons in the treatment of post-TURP SUI. The therapy was found to be safe and efficient. The majority of our study population reported improvement on their condition and greater than or equal to 50% reduction in daily pad use.

Intermittent sacral neuromodulation for idiopathic urgency urinary incontinence in women.

AIMS: SNM has been proven to be effective in the treatment of refractory UUI. Total costs and patient burden due to regular battery changes may prevent broad implementation of this treatment. The aim was to achieve a minimal improvement of 50% in incontinence episodes compared to pre-SNM by using iSNM. METHODS: This prospective cohort study was performed in women with UUI receiving treatment with SNM for a minimum of 6 months. The neurostimulator was programmed to 8 hr "on" and 16 hr "off" per day for 12 weeks. Prior to iSNM, data were collected during no SNM and cSNM. Bladder diaries and various patient reported outcome measures were collected at predetermined time points: 1-5 weeks, and 8, 12, and 16 weeks. Nonparametric tests were used for the statistical analysis. RESULTS: Of the 19 patients 63% showed an improvement of >50% of incontinence episodes during iSNM compared to pre-SNM. Bladder diary parameters showed a difference between pre-SNM and iSNM median (P-value); incontinence episodes/24 hr, 4.1-1.0 (P = 0.04), incontinence severity, 2.0-1.0 (P = 0.001), voiding episodes/24 hr, 13.0-8.0 (P = 0.001), and voided volume, 149-219 ml (P = 0.04). The UDI-6, 50.0-27.8 (P = 0.03), and the IIQ-7 scores, 50.0-9.5 (P = 0.04) also showed a significant improvement. No difference was demonstrated between iSNM and cSNM. CONCLUSIONS: Compared to pre-SNM parameters, iSNM shows an improvement in both objective and subjective outcomes. Specifically no difference was found between iSNM and cSNM, indicating that iSNM could be a feasible and cost-effective alternative. Neurourol. Urodynam. 36:385-389, 2017. © 2015 Wiley Periodicals, Inc.

Transcutaneous Electrical Nerve Stimulation for Treating Neurogenic Lower Urinary Tract Dysfunction: A Systematic Review.

CONTEXT: Transcutaneous electrical nerve stimulation (TENS) is a promising therapy for non-neurogenic lower urinary tract dysfunction and might also be a valuable option in patients with an underlying neurological disorder. OBJECTIVE: We systematically reviewed all available evidence on the efficacy and safety of TENS for treating neurogenic lower urinary tract dysfunction. EVIDENCE ACQUISITION: The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. EVIDENCE SYNTHESIS: After screening 1943 articles, 22 studies (two randomised controlled trials, 14 prospective cohort studies, five retrospective case series, and one case report) enrolling 450 patients were included. Eleven studies reported on acute TENS and 11 on chronic TENS. In acute TENS and chronic TENS, the mean increase of maximum cystometric capacity ranged from 69ml to 163ml and from 4ml to 156ml, the mean change of bladder volume at first detrusor overactivity from a decrease of 13ml to an increase of 175ml and from an increase of 10ml to 120ml, a mean decrease of maximum detrusor pressure at first detrusor overactivity from 18 cmH20 to 72 cmH20 and 8 cmH20, and a mean decrease of maximum storage detrusor pressure from 20 cmH20 to 58 cmH2O and from 3 cmH20 to 8 cmH2O, respectively. In chronic TENS, a mean decrease in the number of voids and leakages per 24h ranged from 1 to 3 and from 0 to 4, a mean increase of maximum flow rate from 2ml/s to 7ml/s, and a mean change of postvoid residual from an increase of 26ml to a decrease of 85ml. No TENS-related serious adverse events have been reported. Risk of bias and confounding was high in most studies. CONCLUSIONS: Although preliminary data suggest TENS might be effective and safe for treating neurogenic lower urinary tract dysfunction, the evidence base is poor and more reliable data from well-designed randomised controlled trials are needed to make definitive conclusions. PATIENT SUMMARY: Early data suggest that transcutaneous electrical nerve stimulation might be effective and safe for treating neurogenic lower urinary tract dysfunction, but more reliable evidence is required.

Tibial Nerve Stimulation for Treating Neurogenic Lower Urinary Tract Dysfunction: A Systematic Review.

CONTEXT: Tibial nerve stimulation (TNS) is a promising therapy for non-neurogenic lower urinary tract dysfunction and might also be a valuable option for patients with an underlying neurological disorder. OBJECTIVE: We systematically reviewed all available evidence on the efficacy and safety of TNS for treating neurogenic lower urinary tract dysfunction (NLUTD). EVIDENCE ACQUISITION: The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. EVIDENCE SYNTHESIS: After screening 1943 articles, 16 studies (4 randomized controlled trials [RCTs], 9 prospective cohort studies, 2 retrospective case series, and 1 case report) enrolling 469 patients (283 women and 186 men) were included. Five studies reported on acute TNS and 11 on chronic TNS. In acute and chronic TNS, the mean increase of maximum cystometric capacity ranged from 56 to 132mL and from 49 to 150mL, and the mean increase of bladder volume at first detrusor overactivity ranged from 44 to 92mL and from 93 to 121mL, respectively. In acute and chronic TNS, the mean decrease of maximum detrusor pressure during the storage phase ranged from 5 to 15cm H2O and from 4 to 21cm H2O, respectively. In chronic TNS, the mean decrease in number of voids per 24h, in number of leakages per 24h, and in postvoid residual ranged from 3 to 7, from 1 to 4, and from 15 to 55mL, respectively. No TNS-related adverse events have been reported. Risk of bias and confounding was high in most studies. CONCLUSIONS: Although preliminary data of RCTs and non-RCTs suggest TNS might be effective and safe for treating NLUTD, the evidence base is poor, derived from small, mostly noncomparative studies with a high risk of bias and confounding. More reliable data from well-designed RCTs are needed to reach definitive conclusions. PATIENT SUMMARY: Early data suggest tibial nerve stimulation might be effective and safe for treating neurogenic lower urinary tract dysfunction, but more reliable evidence is required.

Sacral neuromodulation as treatment for refractory idiopathic urge urinary incontinence: 5-year results of a longitudinal study in 60 women.

PURPOSE: We evaluated the results of sacral neuromodulation after 5-year followup in women with refractory idiopathic urge urinary incontinence. MATERIALS AND METHODS: A neuromodulation system with an original (nontined) lead was implanted by open surgery after a positive percutaneous nerve evaluation in 60 women from 1990 to 2004. Voiding incontinence diary parameters were used to evaluate efficacy. Success was defined as at least a 50% decrease in the number of incontinence episodes or pads used daily. Safety was also evaluated. RESULTS: The success rate gradually decreased from 52 patients (87%) at 1 month to 37 (62%) at 5 years. Complete continence persisted in 15% of patients. The system was still used by 80% of patients at 5 years. In 32 patients a total of 57 adverse events occurred, which were not severe (Clavien grade I and IIIb in 61% and 39%, respectively). CONCLUSIONS: Sacral neuromodulation appears to be a safe technique for refractory idiopathic urge urinary incontinence in women. The success rate gradually decreased to 62% after 5 years with 15% of patients completely continent.

Different brain effects during chronic and acute sacral neuromodulation in urge incontinent patients with implanted neurostimulators.

OBJECTIVE: To compare changes in regional cerebral blood flow (rCBF), using positron emission tomography (PET), during chronic and acute sacral neuromodulation (SN). SN is an effective long-term treatment for chronic urge incontinence due to urinary bladder hyperactivity, as sensory nerves, spinal and supraspinal structures are probably responsible for the action of SN. It is not known which brain areas are involved, and the optimum benefit of SN is not immediate, suggesting that induced plasticity of the brain is necessary. PATIENTS AND METHODS: Brain activity was measured in two groups: 12 urge incontinent patients (11 women and one man; mean age 52 years) in whom an implanted unilateral S3 nerve neurostimulator had been effective for >6 months (mean time after implantation 4.5 years); and eight urge incontinent patients (seven women and one man; mean age 49 years) in whom the neurostimulator was activated for the first time in the PET scanner. RESULTS: During SN in chronically implanted patients, there were significant decreases in rCBF in the middle part of the cingulate gyrus, the ventromedial orbitofrontal cortex, midbrain and adjacent midline thalamus, and rCBF increases in the dorsolateral prefrontal cortex. During acute SN in newly implanted patients, there were significant decreases in rCBF the medial cerebellum, and increases in the right postcentral gyrus cortex, the right insular cortex and the ventromedial orbitofrontal cortex. Group analysis between chronic and newly implanted patients showed significant differences in the associative sensory cortex, premotor cortex and the cerebellum, all three involved in learning behaviour. CONCLUSIONS: These findings suggests that chronic SN influences, presumably via the spinal cord, brain areas previously implicated in detrusor hyperactivity, awareness of bladder filling, the urge to void and the timing of micturition. Furthermore, SN affects areas involved in alertness and awareness. Acute SN modulates predominantly areas involved in sensorimotor learning, which might become less active during the course of chronic SN.