Magdy Hassouna

Long-term results of a multicenter study on sacral nerve stimulation for treatment of urinary urge incontinence, urgency-frequency, and retention☆

Many patients have chronic, debilitating symptoms of voiding dysfunction that are refractory to conventional medical or surgical therapies. This multicenter, prospective study evaluated the long-term effectiveness of sacral nerve stimulation using the implantable Medtronic InterStim therapy for urinary control in patients with otherwise intractable complaints of urinary urge incontinence, urgency-frequency, or retention. Each patient first underwent temporary, percutaneous sacral nerve test stimulation. If at least a 50% reduction in target symptoms was documented for at least 3 days, patients received a permanent Medtronic InterStim sacral nerve stimulation system that includes a surgically implanted lead and neurostimulator. Regular follow-up was conducted with outcome data. We report here on patients who have been observed from 1.5 to 3 years postimplantation. The results demonstrate that after 3 years, 59% of 41 urinary urge incontinent patients showed greater than 50% reduction in leaking episodes per day with 46% of patients being completely dry. After 2 years, 56% of the urgency-frequency patients showed greater than 50% reduction in voids per day. After 1. 5 years, 70% of 42 retention patients showed greater than 50% reduction in catheter volume per catheterization. We conclude that the Medtronic InterStim therapy for urinary control system is an effective therapy with sustained clinical benefit for patients with intractable symptoms of urinary urge incontinence, urgency-frequency, or retention.

SACRAL NERVE ROOT NEUROMODULATION: AN EFFECTIVE TREATMENT FOR REFRACTORY URGE INCONTINENCE

PURPOSE Sacral foramina implants have been recognized recently as a method for treatment of refractory urinary urge incontinence. We study the outcome of the procedure with in-depth analysis of the results of 18 implanted cases. MATERIALS AND METHODS Patients with urinary urge incontinence were subjected to percutaneous nerve evaluation of the S3 roots as a temporary screening test to determine response to neuromodulation. Satisfactory responders were implanted with permanent sacral root neuroprosthesis. The study design included comprehensive voiding diaries for 4 consecutive days twice as a baseline, 1 with percutaneous nerve evaluation screening, 1 after the percutaneous nerve evaluation, 1 at the 1, 3 and 6 post-implantation visits, and every 6 months thereafter. Uroflowmetry and quality of life questionnaires were performed at the same intervals. Urodynamic study was done as a baseline and 6 months after implantation of the neuroprosthesis. RESULTS All 18 patients (16 women and 2 men) with refractory urge incontinence received a sacral foramina neuroprosthesis after demonstrating a good response to the percutaneous nerve evaluation. Average patient age at presentation was 42.3+/-3.3 years (range 22 to 67) and duration of urinary symptoms was 6.6+/-1.3 years (range 1.2 to 18.8). Average followup was 18.8 months (range 3 to 83). Neuromodulation in these patients showed a marked reduction in leakage episodes from 6.49 to 1.98 times per 24 hours and in the leakage severity score. Eight patients became completely dry and 4 had average leakage episodes of 1 or less daily. Patients showed as well a decrease in urinary frequency with an increase in functional bladder capacity. Associated pelvic pain improved substantially. Cystometrograms demonstrated increased volume at first sensation by 50% and increased cystometric capacity by 15% with the disappearance of uninhibited contractions in 1 of the 4 patients who presented with it preoperatively. There was also noticeable improvement in the quality of life. Complication rate was low and none was life threatening. CONCLUSIONS Sacral root neuromodulation is an appealing modality for treatment of urge incontinence refractory to conventional pharmacotherapy. The relative simplicity of the technique, promising results and low complication rate make this therapy a likely alternative.

Sacral root neuromodulation in idiopathic nonobstructive chronic urinary retention.

PURPOSE Sacral root neuromodulation is becoming a superior alternative to the standard treatment of idiopathic nonobstructive urinary retention. We report results in 20 successive patients who underwent sacral foramen implantation to restore bladder function. MATERIALS AND METHODS After an initial, thorough baseline assessment 20 patients 19.43 to 55.66 years old with idiopathic nonobstructive urinary retention underwent percutaneous nerve evaluation. Response was assessed by a detailed voiding diary. Responders underwent implantation with an S3 foramen implant, and were followed 1, 3 and 6 months postoperatively, and every 6 months thereafter. RESULTS Sacral root neuromodulation restored voiding capability in these patients. Bladders were emptied with minimal post-void residual urine, which decreased from 78.3 to 5.5 to 10.2% of the total voided volume from baseline to postoperative followup. These results were reflected in uroflowmetry and pressure-flow studies, which were almost normal after implantation. Furthermore, the urinary tract infection rate decreased significantly and associated pelvic pain improved substantially. The Beck depression inventory and SF-36 quality of life questionnaire indicated some improvement but reached significance in only 1 item. In addition, cystometrography showed no significant difference after 6 months of implantation compared with baseline values. Complications were minimal and within expectations. CONCLUSIONS Sacral root neuromodulation is an appealing, successful modality for nonobstructive urinary retention. Only patients who have a good response to percutaneous nerve evaluation are candidates for implantation. The high efficacy in patients who undergo implantation, relative simplicity of the procedure and low complication rate make this a treatment breakthrough in this difficult group.

Long–Term Effectiveness of Sacral Nerve Stimulation for Refractory Urge Incontinence

Objectives: To evaluate the long–term efficacy of sacral nerve stimulation for refractory urinary urge incontinence. Study Design and Methods: Urge incontinent patients qualified for surgical implantation of a neurostimulator system after trial screening with percutaneous test stimulation. Surgical implantation of the InterStim System (Medtronic Inc., Minneapolis, Minn., USA) was performed in cases where a >50% reduction in incontinence symptoms was documented during the 3– to 7–day test stimulation period. The InterStim System consists of an implantable pulse generator, a transforamenally placed quadripolar lead, and an extension that connects these two devices for unilateral stimulation of the S3 or S4 sacral nerve. Efficacy for 96 implanted patients was based on urinary symptom changes as quantified in voiding diaries collected at baseline and annually after surgical implantation. Results: As compared to baseline, the group of 96 implanted patients demonstrated significant reductions in urge incontinent symptoms at an average of 30.8±14.8 (range 12–60) months with respect to the number of urge incontinent episodes per day, severity of leaking, and the number of absorbent pads/diapers replaced per day due to incontinence (all p<0.0001, respectively). Gender, pretreatment variables, and age were not found to be relevant factors that affected these results. 11 of the 96 patients underwent device explant due to lack of efficacy, pain or bowel dysfunction. These data were conservatively included in the efficacy results. No permanent injuries associated with the devices or therapy were reported. Conclusion: Sacral nerve stimulation is an effective treatment for refractory urge incontinence with sustained long–term benefit through an average of 30.8 months.

Neural Stimulation for Chronic Voiding Dysfunctions

Neural stimulation of the sacral nerve roots could become an acceptable and promising modality in controlling variable forms of difficult voiding dysfunctions. A total of 50 patients who presented with various forms of voiding dysfunction underwent initial screening by percutaneous nerve evaluation of the S3 nerve root guided by movements of the levator ani and toes. Only 17 patients demonstrated a satisfactory response to percutaneous nerve evaluation and subsequent subchronic wire testing for 4 to 5 days, and they were eligible to enter the study. The studied patients (13 women and 4 men) were classified into 2 groups according to presentation. Group 1 included 8 patients who presented mainly with nonobstructive chronic urinary retention. All 8 patients were on intermittent self-catheterization except 1 with a suprapubic tube. The 9 patients in group 2 mainly presented with other forms of voiding dysfunctions, including pain (suprapubic and perineal), frequency and/or urgency. All patients were neurologically free, and had failed pharmacological and surgical attempts to correct the problems. In both groups radiological and ultrasound evaluations of the urinary tract as well as cystourethroscopy were within normal limits. Urodynamic studies were performed preoperatively and postoperatively. Unilateral S3 foramen implantation was performed on the selected side in all patients. Followup ranged from 3 to 52 months. All patients were followed preoperatively and postoperatively by voiding and itemized symptom score diary as well as a quality of life questionnaire. Each symptom and question were given certain grades that reflect the severity or importance to the patient. The symptom scores and the quality of life questionnaires were analyzed preoperatively and postoperatively. In group 1 voided volume (expressed as a percentage of total bladder capacity) was significantly increased at 6 months (23 +/- 7.5% preoperatively versus 81.9 +/- 7.7% postoperatively, p < 0.05) and, accordingly, residual volume (also expressed as a percentage of total bladder capacity) was significantly decreased. The maximum flow rate increased to 18.0 +/- 2.6 ml. per second postoperatively compared to 7.8 +/- 3.1 ml. per second preoperatively. The number of intermittent self-catheterizations per day decreased to 1.3 +/- 0.8 compared to 4.2 +/- 0.6 preoperatively (p < 0.05). Uninhibited bladder contractions with vesicosphincteric dyssynergia disappeared in 1 patient, while they persisted in 1 for up to 6 months. In group 2 the average improvement in pain and difficulty to start voiding was 85%, frequency improved by 37%, urgency by 42%, and leaking episodes and number of diapers per day decreased by 50%. Uninhibited bladder contractions disappeared in 1 patient within 6 months.(ABSTRACT TRUNCATED AT 400 WORDS)

Role of C-afferent fibres in the mechanism of action of sacral nerve root neuromodulation in chronic spinal cord injury

Objective  To determine whether sacral root neuro‐modulation (a promising therapeutic modality in patients with refractory voiding and storage problems) has its effect through the blockade of C‐afferent fibres that form the afferent limb of a pathological reflex arc responsible for the dysfunction of bladder storage.

Urodynamic evaluation of sacral neuromodulation for urge urinary incontinence

To evaluate the urodynamic data before and 6 months after implantation of sacral neuromodulation (SNM, an established treatment for voiding dysfunction, including refractory urge urinary incontinence, UI) and to assess the correlation between the urodynamic data and clinical efficacy in patients with UI.

NEUROMODULATION REDUCES C-FOS GENE EXPRESSION IN SPINALIZED RATS: A DOUBLE-BLIND RANDOMIZED STUDY

PURPOSE Neuromodulation of the sacral nerve roots is effective to treat various voiding dysfunctions, but the underlying mechanism of neuromodulation is not known. The objective of this study is to evaluate whether inhibition of afferent c-fiber activity is the underlying mechanism of sacral nerve root neuromodulation. MATERIALS AND METHODS Twenty-nine female Sprague-Dawley rats weighing 220 to 250 gm. were divided into 4 groups: normal control (normal rats without any procedure; n = 5), sham with saline (spinalized rats at T9 with saline bladder instillation; n = 7), sham with acetic acid (spinalized rats at T9 with acetic acid bladder instillation; n = 8) and stimulation group (spinalized rats at T9 with acetic acid bladder instillation plus electrical stimulation; n = 9). A cystometrogram was performed 10 days after spinal cord transection to confirm the development of bladder hyperreflexia. Bilateral electrode wires were implanted into S1 dorsal foramina and electrical stimulation was performed 8 hours a day for three weeks. The rats were perfused with 4% paraformaldehyde and an immunocytochemical method was used to stain fos-protein that was encoded by c-fos gene. A double-blind method was used in counting fos-protein positive neurons. RESULTS Bladder hyperreflexia developed in all spinalized rats 10 days after spinal cord transection. Peak bladder pressure was found significantly reduced after neuromodulation (30.4 +/- 4.2 cm. water) compared with the same rats before neuromodulation (82.4 +/- 10.2 cm. water; p = 0. 007). The number of fos-protein positive neurons in the L6 spinal cord segment in the neuromodulation group (93.2 +/- 13.3 cells/section) decreased significantly when compared with the sham with acetic acid group (160.6 +/- 25.0 cells/section; p = 0.02). There was no significant difference in c-fos expression between the sham with saline group (90.5 +/- 15.6 cells/section) and the neuromodulation group (p = 0.92). CONCLUSIONS Sacral dorsal root neuromodulation reduces c-fos gene expression and bladder hyperreflexia in spinalized rats, through inhibition of afferent c-fiber activity.

Pathophysiology of overactive bladder.

Overactive bladder (OAB) is a common disorder that negatively affects the quality of life of our patients and carries a large socioeconomic burden. According to the International Continence Society, it is characterized as urinary urgency, with or without urge incontinence, usually, with frequency and nocturia in the absence of causative infection. The pathophysiology of this disease entity varies between neurogenic, myogenic, or idiopathic factors. This paper provides a review of the contemporary theories behind the pathophysiology of OAB.

Neuromodulation reduces urinary frequency in rats with hydrochloric acid-induced cystitis

Objective To evaluate the effect of sacral neuromodulation on interstitial cystitis (IC) and determine the underlying mechanism of neuromodulation in the treatment of IC.