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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.

Acute Disease↗

Permanent sacral nerve modulation for fecal incontinence and associated urinary disturbances.

BACKGROUND AND AIMS: Sacral nerve modulation (SNM) using an implantable pulse generator is gaining increasing acceptance in the treatment of several functional disturbances of the urinary and intestinal tract. This new therapeutic approach offers new possibilities in the treatment of fecal incontinence (FI) by means of its possible effects on anorectal physiology. PATIENTS AND METHODS: Fourteen patients with FI, six of whom had associated urinary disturbances, underwent permanent SNM after successful peripheral nerve evaluation tests. All had a clinical evaluation including FI grading systems (American Medical systems, AMS; Continence Grading System, CGS) and quality of life questionnaires (Fecal Incontinence Quality of Life, FIQL), and anorectal physiology tests performed before and during electrostimulation. Two patients had a lead displacement which was repositioned. Median follow-up was 14 months (range 6-48 months). RESULTS: AMS scores decreased significantly from 101 to 67 after 24 months CGS scores from 15 to 2 after 2 months. The median number of episodes of major incontinence per 2 weeks decreased from 14 to 1 after 24 months. FIQL scores improved significantly in the nine patients tested from an overall score of 1.59 to 3.3, with improvement in all areas of the FIQL. Four of the six patients with associated urinary disturbances had a significant improvement in their symptoms. Anal resting and squeezing tone did not change significantly, nor did rectal volumetry, compliance, rectoanal inhibitory reflex, or length of the anal high-pressure zone, while 24-h rectal manometry showed inhibition of the spontaneous rectal motility complexes after meal and on awakening in the only two patients undergoing this investigation. CONCLUSION: Although the mechanism of action of SMN is still unclear and requires further investigations, clinical results are very encouraging, confirming the role of this new and safe procedure in the treatment of FI and associated urinary disturbances.

Adult↗

Efficacy and safety of sacral nerve stimulation for urinary urge incontinence: a systematic review.

PURPOSE: We systematically reviewed the evidence on the efficacy and safety of sacral nerve stimulation (SNS) for severe urge incontinence. MATERIALS AND METHODS: A systematic review was performed of primary studies of SNS for urge incontinence published in English between 1966 and May 2003, and identified in major electronic databases. Two reviewers independently selected studies, assessed their methodological quality and extracted data. RESULTS: Four randomized controlled trials and 30 case series were identified. Evidence from the randomized controlled trials, involving approximately 120 patients, showed that about 80% achieved continence or greater than 50% improvement in their main incontinence symptoms after SNS compared with about 3% of controls receiving conservative treatments while waiting for an implant. While case series were larger, they were methodologically less reliable. However, they showed similar results with 67% of patients becoming dry or achieving a greater than 50% improvement in symptoms after implantation. Incontinence episodes, leakage severity, voiding frequency and pad use were significantly lower after implantation. Benefits were reported to persist 3 to 5 years after implantation. Adverse events were documented in 27 studies. Overall the reoperation rate in implanted cases was 33%. The most common reason for surgical revision was relocation of the generator because of pain and infection. Common complications were pain at the implant or lead site in 25% of patients, lead related problems such as lead migration in 16%, replacement and repositioning of the implanted pulse generator in 15%, wound problems in 7%, adverse effects on bowel function in 6%, infection in 5% and generator problems in 5%. Permanent removal of the electrodes was reported in 9% of patients. Technical changes with time have been associated with decreased complication rates. CONCLUSIONS: There is evidence indicating that SNS is effective for decreasing symptoms in patients with urge incontinence. Adverse events occurred in about half of the implanted cases and surgical revision was performed in 33%. No major irreversible complications were reported in the studies reviewed. Further research is required on the long-term effects of and quality of life in patients with SNS.

Adult↗

Sacral neuromodulation for neurogenic bladder dysfunction in children.

PURPOSE: We report a prospective randomized controlled study to evaluate the possible benefits of sacral neuromodulation (SNM) for the management of neurogenic bladder dysfunction in children. MATERIALS AND METHODS: We included in the study subjects between the ages of 5 and 21 years presenting with urinary incontinence due to neurogenic bladder. Before study inclusion all previous treatment was discontinued. Patients were randomly divided into the control group treated conventionally and the implant group treated with SNM. Treatment outcome was compared every 3 months for a minimum of 12 months based on clinical examination, voiding diary and urodynamic evaluation. RESULTS: A total of 26 boys and 16 girls with a mean age of 11.9 years were enrolled in this study. There were 21 patients in each group. The main underlying etiology was spina bifida. The 2 groups were comparable with regard to sex, age and urodynamic variables. Total disappearance of urinary leakage was observed in 1 patient who underwent implantation but he still required intermittent catheterization. Comparison of urodynamic variables disclosed no significant statistical difference except with regard to functional bladder capacity which was better in the control group and the leak point pressure which was better in the implant group (p <0.05). Evaluation of interindividual variations in the implant group revealed significant improvement in compliance and functional bladder capacity at 6 and 9 months but not at 12 months. Nine patients in the implant group reported improvement in intestinal transit, 5 total disappearance of urinary infection and 6 persistent sensation of a full bladder. No patient in the control group reported any improvement. Revision surgery was required in 3 cases due to lead migration, faulty connection and wound infection. CONCLUSIONS: SNM is a promising new therapeutic modality. Implant placement is minimally invasive, nondestructive and reversible. Use in children with neurogenic bladder has not been previously reported. Although some improvement was noted in patients treated with SNM, the difference with the control group was not significant. A larger multicenter study is warranted to evaluate SNM.

Adolescent↗

Responses of rat sacral spinal neurons to mechanical and noxious thermal stimulation of the tail.

In this study we investigated the receptive field properties, responses to mechanical and thermal stimuli, and sensitivity to systemic administration of pentobarbital sodium and morphine of single neurons recorded in the sacral spinal cords of pentobarbital-anesthetized rats. Fifty-three neurons responded to innocuous mechanical stimulation of the tail. Of 45 neurons that were additionally tested with noxious thermal stimulation, 62% responded and were classified as wide-dynamic-range or multireceptive neurons. Recording sites were located mainly in the middle layers of the S2-S4 dorsal horn. Mechanosensitive receptive fields on the tail varied widely in size (range 0.14-35 cm2, mean 10.33 cm2) and form, and were in nearly all cases bilateral. Most neurons responded with a high-frequency discharge followed by a more slowly adapting response to pressure stimuli delivered with von Frey hairs. Responses (maximal frequency and total number of impulses) increased in a graded manner to pressure stimuli ranging from 1.2 to 447 g. For neurons responsive to noxious heating of the tail, responses increased in a linear manner over the range of 38-54 degrees C and often leveled off at higher temperatures. Of nine neurons tested with both graded von Frey and noxious heat stimuli, mean responses (maximal frequency and total number of impulses) evoked by the strongest pressure stimuli were larger than those evoked by the most intense heat stimuli, but the difference was not statistically significant. Responses to repeated 48 degrees C stimuli were significantly attenuated within 8 min after systemic administration of morphine (1 or 2 mg/kg ip), reaching maximal suppression (to 37.3%; N = 13) after 18 min, with recovery following systemic naloxone. After morphine (1 and 2 mg/kg ip), the slope of the population stimulus-response function for noxious heat was reduced (51.8%), and the threshold was increased (by 4 degrees C). Responses to noxious heat were significantly depressed (to a mean of 54%; N = 10) by supplemental administration of pentobarbital (mean 17 mg/kg over 5 min). On the basis of similarities between the present data and previous behavioral measures of tail flick stimulus-response functions and their modulation, it is suggested that some of the present neurons might function as interneurons in the tail flick reflex arc.

Analysis of Variance↗

Sacral root neuromodulation in the treatment of refractory urinary urge incontinence: a prospective randomized clinical trial.

OBJECTIVES: To compare the effectiveness of sacral root neuromodulation with that of conservative management in ameliorating symptoms of refractory urinary urge incontinence and enhancing quality of life, to assess the objective response to neuromodulation as revealed by urodynamic testing, and to delineate the long-term outcomes of neuromodulation. METHODS: Forty-four patients with refractory urge incontinence were randomized to undergo neuromodulation with an implantable impulse generator (n = 21) or to continue their prior conservative management (n = 23). At 6 months the control group was eligible for crossover to implant. Patient evaluation included voiding diaries, quality of life questionnaires, urodynamic testing, and documentation of adverse events. Long-term follow-up evaluations were conducted at 6-month intervals up to 36 months. RESULTS: At 6 months mean leakage episodes, leakage severity and pad usage in the implant group were significantly lower by 88% (p < 0.0005), 24% (p = 0.047) and 90% (p < 0.0005), respectively, than the corresponding control group mean values. Improvements in leakage episodes and pad usage of >/=90% were attained by 75 and 85% of the implant group, respectively, but none of the control group. One third of implant patients, but none of the control patients, achieved >/=50% improvement in leakage severity. Over half of the implant patients (56%) were completely dry compared with 1 control patient (4%). Implant patients, but not control patients, exhibited significant improvement with respect to two quality of life measures. Neuromodulation resulted in increases of 220% (p < 0.0005) and 39% (p = 0.013), respectively, in urodynamically assessed bladder volume at first contraction and maximum fill. At 36 months the actuarial rate of treatment failure was 32.4% (95% CI, 17.0-56.0%). Adverse events most frequently involved pain at the implant site, and the incidence of serious complications was low. CONCLUSIONS: Neuromodulation is markedly more effective than conservative management in alleviating symptoms of refractory urge incontinence. Quality of life and urodynamic function are also improved by neuromodulation. The effects of neuromodulation are long-lasting, and associated morbidity is low.

Adult↗

Ropivacaine produces sensory blockade in the lumbar sacral region more frequently than mepivacaine in lower thoracic epidural anesthesia.

PURPOSE: The first sacral nerve has the largest diameter among the spinal nerves and is resistant to local anesthetics. Ropivacaine is a newly developed local anesthetic. There is a possibility that a difference in chemical properties between ropivacaine and other local anesthetics produces a difference in the blockade of the S1 dermatome by lower thoracic epidural anesthesia. Mepivacaine, 2%, is frequently used for epidural anesthesia and produces a level of blockade similar to that of bupivacaine, 0.5%. The purpose of this study was to examine the sensory blockade in the sacral region induced by ropivacaine with that induced by mepivacaine administered in the lower thoracic epidural space. METHODS: Eighteen adults undergoing lower thoracic epidural anesthesia (thoracic 11/12 interspace) were studied in a double-blind fashion. Patients were assigned to one of two groups: those who received 2% mepivacaine, 18 ml (group M; n = 9), and those who received 1% ropivacaine, 12 ml (group R; n = 9). The cephalad levels of sensory blockade to cold, pinprick, and touch in the L2, S1, and S3 dermatomes were assessed at 10, 20, and 35 min after injection. RESULTS: There were no differences in the cephalad levels of sensory block to cold (T4 [range, T4-T2] and T4 [range, T6-T2]), pinprick (T4 [range, T6-T4] and T4 [range, T6-T4]), or touch (T6 [range, T6-T4] and T6 [range, T6-T4]) between group M and group R respectively, at 35 min (P > 0.05). In the L2 and S3 dermatomes, there were no significant differences in the numbers of patients who obtained sensory block to cold or pinprick at 20 and 35 min after study drug administration. However, in the S1 dermatome, significantly higher numbers of patients in group R obtained sensory block to cold at 20 and 35 min after study drug administration than in group M (8 and 0; 9 and 0; P = 0.001 and P < 0.001; 20 min and 35 min after administration, respectively). Also in the S1 dermatome, significantly higher numbers of patients in group R obtained sensory block to pinprick at 20 and 35 min after study drug administration than in group M (6 and 0; 9 and 0; P = 0.027 and P < 0.001; 20 min and 35 min after administration, respectively). A significantly higher number of patients in group R had sensory block to touch in the S3 dermatome at 35 min (7 and 2; group R and group M, respectively; P = 0.01). CONCLUSION: Ropivacaine, 1%, administered in the lower thoracic epidural space, induces sensory blockade to cold and pinprick in the S1 dermatome more frequently than 2% mepivacaine.

Adult↗

Medium-term experience of sacral neuromodulation by tined lead implantation.

OBJECTIVE: To describe patient selection for sacral neuromodulation, also known as Interstim therapy, and the results of tined-lead implantation in the medium term. PATIENTS AND METHODS: In all, 49 patients, 39 with refractory overactive bladder symptoms and 10 with urinary retention, were implanted with the tined lead under local anaesthesia. The mean (sd) test period was 12.4 (5.8) days. Patients were implanted when they had a > or = 50% improvement in voiding diary variables during the test period. The mean follow-up for implanted patients was 15.5 (7.9) months. Changes in voiding variables were compared using a t-test. RESULTS: Ten patients had a one-stage and 39 a two-stage implant; of the latter group, 31 (80%) had a positive response and eight (21%) did not. In all, 31 patients were included in the follow-up. At the last follow-up, 28 (90%) patients had a >50% improvement in diary variables and three (10%) did not. In 21 patients with urgency symptoms the mean (sd) number of voids decreased from 11.7 (8.9)/day at baseline to 7.3 (3.4)/day (P = 0.1); the voided volume increased from 160.2 (70.7) mL to 231.1 (119.5) mL (P = 0.001); and the number of leakages decreased from 9.5 (8.7) to 3.3 (2.2)/day (P = 0.17). In the 10 patients with retention, the number of catheterizations decreased from 5.44 (1.6)/day with a volume of 297.6 (76.8) mL, to 1.2 (1.7)/day and 111.6 (158.1) mL; the mean number of voids increased from 3.7 (3.8)/day with a volume of 123.3 (141.7) mL, to 4.2 (2.4)/day and 248.3 (146.0)mL. There were no significant differences in the variables in the patients with retention. Seven patients had an adverse event. There was one incomplete electrode migration that was treated conservatively. CONCLUSION: This new minimally invasive approach gives positive results in the medium term. Two-stage testing with the tined lead seems more reliable than the classic percutaneous nerve evaluation. The lead anchoring method seems sufficient for fixing the electrode in the medium term.

Adolescent↗