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Introduction: : Sacral neuromodulation (SNM) is an effective treatment modality for several urological problems, including neurogenic bladder. However, the invasiveness of this technique makes it unsuitable for many patients. We present a novel transdermal amplitude-modulated signal (TAMS) that may provide a non-invasive alternative to implantable SNM to treat neurogenic detrusor overactivity (NDO)., Methods: : In this study, we investigated the mechanism of action of non-invasive SNM using TAMS on our established spinal cord injury (SCI) animal model. We demonstrated that spinally transected rats develop urinary bladder hyper-reflexia after 3 weeks of SCI, indicated by the presence of uninhibited contractions, increased resting pressure, increased threshold pressure and increased maximum voiding pressure., Results: : Short-term neurostimulation affected urodynamics parameters by significantly reducing the threshold pressure (p = 0.02). Spinal transection also increased calcitonin gene-related protein (CGRP) concentration in the L6 dorsal root ganglia; whereas, neurostimulation significantly reduced CGRP concentration in L6 (p = 0.03)., Conclusion: : TAMS caused a reduction in NDO by inhibiting C-fibre activity.

Objective: To assess the significance of onabotulinumtoxinA (onabotA) intravesical administration in blocking autonomic dysreflexia (AD) response induced by cystometrogram (CMG) after T4 spinal cord transection (SCT)., Materials and Methods: Female rats were stratified into three groups: a sham group; a SCT-only group; and a SCT with onabotA treatment group. Each group was further subdivided into two subgroups: AD assessment, or nerve growth factor (NGF) assessment via enzyme-linked immunosorbent assay (ELISA). Three weeks after T4-SCT, all groups were assessed. Arterial pressure and heart rate were measured during and after CMG. NGF was also extracted from the bladder and the dorsal root ganglia (DRG) of the T4 root and quantified by ELISA. In the onabotA-treated group, 48 h before assessment, onabotA (1 mL, 20 U/mL in saline) was given using a urethral tube and was left indwelling for 30 min. Univariate anova was used to analyse the data and statistical significance was set at P < 0.05., Results: The maximum voiding pressure and the number of uninhibited contractions were significantly lower in the group treated with intravesical onabotA than in the SCT-only group. Intravesical onabotA significantly blocked the dysreflexia response (high arterial pressure with bradycardia) induced by CMG after SCT. Intravesical onabotA also significantly lowered NGF concentrations in the bladder and the T4 DRG segment., Conclusions: The results of the present study showed that intravesical onabotA controls neurogenic detrusor overactivity and AD after SCT. The findings shed light on the potential benefits of intravesical onabotA treatment in patients with spinal cord injury, and also provide a novel mechanism for the control of AD via a minimally invasive treatment modality., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Aims: This study was sought to evaluate the efficacy and durability of sacral neuromodulation in the treatment of bladder pain syndrome (BPS) patients., Methods: A retrospective chart review was performed of patients who had unilateral sacral nerve stimulator (InterStim®) for refractory BPS between June 2002 and December 2004. Patients were qualified for permanent implantation by showing ≥ 50% improvement in their bladder pain and voiding symptoms 1-week post-percutaneous nerve evaluation (PNE). Voiding diary was completed at pre-implantation, 1 year, and on the last visit. Urinary distress inventory short form was completed pre-implantation and on the last visit. Bladder pain was evaluated by visual analogue scale. Primary outcome was improvement in bladder pain. Differences among groups were compared by one-way ANOVA and t-test. Statistical significance was set at P ≤ 0.05., Results: Twenty-one female patients diagnosed with BPS had PNE; 11 patients (52%) showed ≥ 50% improvement in their bladder pain and voiding symptoms and they consider candidates for permanent implantation (Table I), while 10 patients (48%) failed to show 50% improvement in their voiding symptoms or bladder pain (Table II). In those 11 patients who underwent permanent implantation, the average patient's age was 44.3 ± 8.9 years; average time since diagnosis was 3 ± 0.8 years; the average follow- up was 71.5 ± 9.3 months (Table III). There was significant improvement in the bladder pain and voiding parameters at 1-year follow-up, which was maintained at 5-year follow-up. There was continuous improvement in urgency (1.2 ± 0.68) at 1-year follow-up, and (0.98 ± 0.72) at the last visit. Average voided volume was also continuously improved from 242 ± 62.7 ml at 1-year follow-up to 276 ± 64.7 ml on the last visit., Conclusion: Sacral neuromodulation as part of multimodal treatment provides an effective long-term treatment option for sub-group of refractory BPS., (Copyright © 2011 Wiley-Liss, Inc.)

Objectives:   This study sought to determine the association between stimulation parameters at the time of implantation and loss of efficacy on long-term follow-up., Material and Methods:   Between 2002 and 2007, 143 patients underwent selective sacral nerve root stimulation at our center as a treatment for voiding dysfunction. Nine patients were explanted because of loss of efficacy. The patients' charts were retrospectively reviewed and compared with those of a well-matched group of 12 positive responders. A t-test was used to determine the differences in voiding parameters and stimulation parameters between both groups (at p < 0.05)., Results:   The baseline amplitude levels in the loss of efficacy group were significantly higher than those of the control group (2.08 ± 0.35 V vs. 1.27 ± 0.25 V) (p= 0.008). The impedance levels were significantly higher in the loss of efficacy group than the control (1032.4 ± 181 Ω vs. 590 ± 44.6 Ω) (p= 0.025)., Conclusion:   High stimulation parameters at the time of implantation were associated with loss of efficacy at the long-term follow-up., (© 2011 International Neuromodulation Society.)

The lower urinary tract dysfunction encompasses voiding, postvoiding, and storage symptoms. Conventional treatment modalities include pharmacotherapy and behavioural therapy. Sacral neuromodulation (SNM) is a safe and minimally invasive treatment modality that has recently gained wide acceptance in the management of urinary urge incontinence, urge frequency, and nonobstructive urinary retention, in particular, among those patients with conditions refractory to conventional methods. We searched multiple electronic databases through June 30, 2009 for eligible studies. We examined published clinical and experimental studies concerning the mechanisms of action of SNM. In the first part of the manuscript, we describe the anatomy and functions of the lower urinary tract including the reflexes involved in its functions and then review the pathophysiology of major types of the lower urinary tract dysfunction. In the second part, we discuss different ways for SNM to control various types of voiding dysfunction. The lower urinary tract dysfunctions affect millions of people worldwide and have a severe impact on their quality of life. SNM offers a safe and minimally invasive modality in the treatment of voiding dysfunctions, especially in patients with conditions refractory to conventional therapies.

Objective: To examine the voiding behaviour changes in rats with bladder outlet obstruction (BOO) while inhibiting matrix metalloproteinase (MMP) activity with doxycycline, as increased MMP activity may be involved in obstruction-induced bladder hypertrophy., Materials and Methods: Female Sprague-Dawley were divided into eight groups (three rats in each group): normal control (NC) +/- doxycycline, 3 weeks partial BOO (3WPBOO) +/- doxycycline, 6 weeks PBOO +/- doxycycline, and 3 weeks PBOO followed by 3 weeks de-obstruction (3WOD) +/- doxycycline. All rats received the same food and water and were on the same 12 h dark/light cycle housed in metabolic cages. Treatment groups were given doxycycline 15 mg/kg/day subcutaneously twice daily. The voiding variables measured were average voided volume (AV V) and voiding frequency (VF) in 24 h. After completion of the voiding behaviour studies, the rats were killed and their bladders were excised and weighed., Results: The AV Vs were significantly increased (P < 0.05) in all study groups compared with the NC group except for the 3WPBOO-doxycycline and 3WOD-doxycycline groups. The VF was significantly increased (P < 0.05) only in the 3WOD-doxycycline group. The bladder weights were significantly increased after PBOO in all the study groups (P < 0.05), except for the 3WOD group., Conclusion: These data show that MMP inhibition may affect voiding behaviour during the response to BOO or its relief. This is the first clinical demonstration that interfering with a principal target of bladder muscle wall remodelling may have a direct effect on bladder function.

Introduction: Pelvic neuromodulation is an established method of treating voiding dysfunction. Little is known about the pathophysiology associated with voiding dysfunction. Reports have suggested that a delay in treating patients with sacral neuromodulation therapy can impact the success rate of this type of treatment in voiding dysfunction. We examined patient response to pelvic neuromodulation when it was applied early versus late in the postdiagnosis of voiding dysfunction., Methods: We conducted a retrospective study of 42 patients (38 women and 4 men) with voiding dysfunction who underwent surgery for implant with the Interstim (Medtronic, Minneapolis, Minn.). Prior to implantation, patients were required to pass a percutaneous nerve evaluation (PNE) over a 1-week period. Patients were observed for 20-48 months postimplantation. All patients recorded their voiding parameters at baseline, after screening and every 6 months thereafter. Twenty patients (in the early group) underwent implant surgery with the neurostimulator 2-4 weeks post-PNE, and 22 patients (the late group) had the device implanted 6-24 months post-PNE owing to local logistical circumstances., Results: In the early group, 16 of 20 patients (80%) maintained a good response. In the late group, 13 of 22 (59%) patients showed a good response. Groups were well matched in terms of age, duration of voiding dysfunction and incidence of comorbidity., Conclusion: Patients who were delayed more than 6 months in receiving the neurostimulator implant showed a worse response than did patients who had the device implanted soon after PNE. This indicates the possibility of disease progression, which may limit the response to sacral neuromodulation.

Objectives: Sacral neuromodulation has become an established method to treat voiding dysfunction. Currently the use of implanted sacral nerve stimulators is becoming more popular worldwide. Magnetic resonance imaging (MRI) is an important diagnostic tool for many medical and neurological disorders. Many radiology centers do not perform MRI examinations on patients with implanted sacral nerve stimulator. The basis for this policy is that potential hazards such as motion, dislocation or torquing of the implanted pulse generator (IPG), heating of the leads, and damage to the IPG may occur, resulting in painful stimulation. In contrast, many studies conducted on MRI at 1.5Tesla in patients with implantable devices have found the examination to be safe if the area to be imaged is out of the isocenter of the MRI scanner and other precautions are taken., Methods: Eight MRI examinations at 1.5Tesla were conducted in areas outside the pelvis on six patients with implanted sacral nerve stimulator (InterStim neurostimulator; Medtronic, Inc, Minneapolis, MN, USA). Implanted pulse generators were examined before and after MRI procedures. All patients had their parameters recorded; then the IPGs were put to "nominal" status. Patients were monitored continuously during and after the procedure. After the MRI session, the site of the implanted device was examined and changes were reported. Devices were then re-programmed to their previous setup with the use of a programmer (model 7432; Medtronic, Inc). Voiding diaries were collected after MRI procedures and compared with previous records., Results and Conclusion: During the MRI session, no patient showed symptoms that required stopping the examination. There was no change in perception of the stimulation after re-programming of the implanted sacral nerve stimulator, according to patients' feedback. Devices were functioning properly, and no change in bladder functions was reported after MRI examinations. Finally, we hope that presenting these cases will encourage performance of more comprehensive studies on implanted sacral nerve stimulators on a larger patient population in the near future.