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PubMed1998

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.

Adult↗

PubMed1998

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.

Adult↗

PubMed2001

Sacral nerve neuromodulation in the treatment of refractory motor urge incontinence.

Sacral nerve neuromodulation may be an effective treatment option in patients with motor urge incontinence when conservative therapy fails. The effect of treatment is durable in the majority of patients, but there is also a high failure rate. The cause of failure remains unclear in most cases as it is still unknown exactly how neuromodulation works. The present review summarizes the results of patient treatment and research into the working mechanism of neuromodulation, as well as the technical developments described in the past year.

Electric Stimulation Therapy↗

PubMed2004

Sacral neuromodulation for refractory detrusor overactivity in women with an artificial urinary sphincter.

PURPOSE: We assessed the efficacy of sacral neuromodulation as an alternative therapeutic option in women with an artificial urinary sphincter (AUS) who had de novo irritative urinary symptoms (urgency/frequency) refractory to conventional treatment. MATERIALS AND METHODS: Between 1984 and 2002 we implanted an AUS in 350 women and detrusor overactivity developed in 14. Six of the 14 patients responding positively to a percutaneous nerve evaluation test (greater than 50% subjective/objective improvement) were implanted with an S3 neuromodulator within 42.8 weeks (range 21 to 106) of AUS implantation. Followup included analysis of the voiding diary, a pad test and urodynamic assessment. RESULTS: After 30.5 months followup (range 14 to 40) 1 patient was dry, 4 were improved and treatment failed in 1. At 12 months mean voiding frequency daily had decreased from 17 (range 12 to 23) to 8 (range 4 to 12) and the mean number of leakages episodes daily had decreased from 14.7 (range 8.5 to 17) to 6 (range 4 to 10). Mean voided volume had increased from 121.7 (range 90 to 170) to 180 ml (range 120 to 225), mean first desire to void volume had increased from 117 (range 88 to 190) to 183 ml (range 130 to 275) and mean functional bladder capacity had increased from 325 (range 200 to 530) to 372 ml (range 250 to 580). Uninhibited bladder contractions had resolved in 4 of 5 patients. CONCLUSIONS: In women who already have an AUS with urge incontinence sacral neuromodulation can help resolve symptoms. Because this therapy does not compromise the potential for future treatment, it appears to be an alternative option in these patients. It can postpone or avoid more mutilating surgery and self-catheterization.

Adult↗

PubMed2005

Aging neuromodulation impairs associative binding: a neurocomputational account.

Relative to young adults, older adults are particularly impaired in episodic memory tasks requiring associative binding of separate components into compound episodes, such as tasks requiring item-context and item-item binding. This associative-binding deficit has been attributed to senescent changes in frontal-hippocampal circuitry but has not been formally linked to impaired neuromodulation involving this circuitry. Previous neurocomputational work showed that impaired neuromodulation could result in less distinct neurocognitive representations. Here we extend this computational principle to simulate aging-related deficits in associative binding. As expected, networks with simulated deficiency in neuromodulation resulted in less distinct internal representations than did networks simulating the processing and performance of young adults, and were also more impaired under task conditions that required associative binding. The findings suggest that senescent changes in neuromodulatory mechanisms may play a basic role in aging-related impairment in associative binding by reducing the efficacy of distributed conjunctive coding.

Aged↗

PubMed2005

Objective measurement of bladder sensation: use of a new patient-activated device and response to neuromodulation.

Detrusor overactivity is the primary objective focus of most investigations into the diagnosis and management of patients with urgency incontinence. Patients with an overactive bladder are characteristically troubled by subjective sensations of bladder fullness and urinary urgency, and frequently void at low bladder volumes attained before noticeable detrusor overactivity occurs. Bladder sensations are therefore crucial to understanding voiding patterns and symptoms, but little progress has been made in objectively describing the range of these sensations, and adequate information is lacking about their response to neuromodulation. Towards this end, a keypad 'urge score' device was designed to measure sensations during bladder filling. This patient-activated device gathers information about patient perceptions of bladder filling and the successive stages of increasing bladder sensation, without prompting or intervention by the investigator. The accuracy of the 'urge keypad' during filling cystometrography was validated in patients with urgency incontinence, and compared with data abstracted from patient voiding diaries. The device provides reliable and repeatable measures of different bladder sensations, with excellent, statistically significant consistency between bladder volumes and corresponding levels of sensation. Subsequently, it was shown that the sensation of urgency can be suppressed by neuromodulation in most patients tested; this suppression occurs with improvements in bladder capacity and voided volumes. It is therefore suggested that urodynamics with concurrent sensory evaluation may offer a more useful assessment tool for selecting those patients for therapies such as neuromodulation who present predominantly with the symptom of urgency.

Adult↗

PubMed2003

Neuroprotection trek--the next generation: neuromodulation I. Techniques--deep brain stimulation, vagus nerve stimulation, and transcranial magnetic stimulation.

Neuromodulation denotes controlled electrical stimulation of the central or peripheral nervous system. The three forms of neuromodulation described in this paper-deep brain stimulation, vagus nerve stimulation, and transcranial magnetic stimulation-were chosen primarily for their demonstrated or potential clinical usefulness. Deep brain stimulation is a completely implanted technique for improving movement disorders, such as Parkinson's disease, by very focal electrical stimulation of the brain-a technique that employs well-established hardware (electrode and pulse generator/battery). Vagus nerve stimulation is similar to deep brain stimulation in being well-established (for the treatment of refractory epilepsy), completely implanted, and having hardware that can be considered standard at the present time. Vagus nerve stimulation differs from deep brain stimulation, however, in that afferent stimulation of the vagus nerve results in diffuse effects on many regions throughout the brain. Although use of deep brain stimulation for applications beyond movement disorders will no doubt involve placing the stimulating electrode(s) in regions other than the thalamus, subthalamus, or globus pallidus, the use of vagus nerve stimulation for applications beyond epilepsy-for example, depression and eating disorders-is unlikely to require altering the hardware significantly (although stimulation protocols may differ). Transcranial magnetic stimulation is an example of an external or non-implanted, intermittent (at least given the current state of the hardware) stimulation technique, the clinical value of which for neuromodulation and neuroprotection remains to be determined.

Animals↗

PubMed2005

Intravesical heparin and peripheral neuromodulation on interstitial cystitis.

INTRODUCTION: We wanted to evaluate the therapeutic effect of intravesical heparin and peripheral neuromodulation on patients with interstitial cystitis. MATERIALS AND METHODS: From March 2002 to August 2003, 8 female and 2 male subjects conform to the NIDDK criteria and not responsive to the previous conventional treatments were included in the study. Wisconsin pain scores, maximal cystometric capacities, and night and day voiding frequencies were determined and these studies were repeated in the 2nd and 12th months of the treatment with 10,000 units intravesical heparin and peripheral neuromodulation. Frequency of the treatment was once a week during first 8 weeks, once in 2 weeks in the following 8 weeks, and once in 3 weeks four times. Then, it was decreased to once a month. RESULTS: The mean follow-up period was 13 months (12-16 months). Day and night voiding frequency were significantly better in the 2nd and 12th months, when compared to pretreatment values. The Wisconsin pain scores were 62.5 +/- 13.9% and 62.8 +/- 15.2% in the 2nd and the 12th months, respectively. The average increase in the maximum cystometric capacity was 54.8 +/- 27.4% and 52.5 +/- 31.6% in the 2nd and the 12th months, respectively. CONCLUSIONS: Intravesical heparin and peripheral neuromodulation combination seems to be an alternative for patients with interstitial cystitis not responsive to other treatments.

Administration, Intravesical↗

PubMed2003

Sympathetic augmentation in hypertension: role of nerve firing, norepinephrine reuptake, and Angiotensin neuromodulation.

There is growing evidence that essential hypertension is commonly neurogenic and is initiated and sustained by sympathetic nervous system overactivity. Potential mechanisms include increased central sympathetic outflow, altered norepinephrine (NE) neuronal reuptake, diminished arterial baroreflex dampening of sympathetic nerve traffic, and sympathetic neuromodulation by angiotensin II. To address this issue, we used microneurography and radiotracer dilution methodology to measure regional sympathetic activity in 22 hypertensive patients and 11 normotensive control subjects. The NE transport inhibitor desipramine was infused to directly assess the potential role of impaired neuronal NE reuptake. To evaluate possible angiotensin sympathetic neuromodulation, the relation of arterial and coronary sinus plasma concentrations of angiotensin II to sympathetic activity was investigated. Hypertensive patients displayed increased muscle sympathetic nerve activity and elevated total systemic, cardiac, and renal NE spillover. Cardiac neuronal NE reuptake was decreased in hypertensive subjects. In response to desipramine, both the reduction of fractional transcardiac 3[H]NE extraction and the increase in cardiac NE spillover were less pronounced in hypertensive patients. DNA sequencing analysis of the NE transporter gene revealed no mutations that could account for reduced transporter activity. Arterial baroreflex control of sympathetic nerve traffic was not diminished in hypertensive subjects. Angiotensin II plasma concentrations were similar in both groups and were not related to indexes of sympathetic activation. Increased rates of sympathetic nerve firing and reduced neuronal NE reuptake both contribute to sympathetic activation in hypertension, whereas a role for dampened arterial baroreflex restraint on sympathetic nerve traffic and a peripheral neuromodulating influence of angiotensin II appear to be excluded.

Action Potentials↗

PubMed2001

Increasing sensor flexibility through neuromodulation.

Both biological and man-made motor control networks require input from sensors to allow for modification of the motor program. Real sensory neurons are more flexible than typical robotic sensors because they are dynamic rather than static. The membrane properties of neurons and hence their excitability can be modified by the presence of neuromodulatory substances. In the case of a sensory neuron, this can change, in a functionally significant way, the code used to describe a stimulus. For instance, extension of the neuron's dynamic range or modification of its filtering characteristics can result. This flexibility has an apparent cost. The code used may be situation-dependent and hence difficult to interpret. To address this issue and to understand how neuromodulation is used effectively in a motor control network, I am studying the GPR2 stretch receptor in the crustacean stomatogastric nervous system. Several different neuromodulatory substances can modify its encoding properties. Comparisons of physiological and anatomical evidence suggest that neuromodulation can be effected both by GPR2 itself and by other neurons in the network. These results suggest that the analog of neuromodulation might be useful for improving sensor performance in an artificial motor control system.

Animals↗

PubMed2000

Sacral neuromodulation in the treatment of urgency-frequency symptoms: a multicenter study on efficacy and safety.

PURPOSE: Neuromodulation of sacral nerves has shown promising results in correcting voiding dysfunction. We report the results of a multicenter trial designed to assess the efficacy of sacral nerve neuromodulation in patients presenting with refractory urinary urgency-frequency. MATERIALS AND METHODS: A total of 51 patients from 12 centers underwent baseline assessment, including a detailed voiding diary, urodynamic evaluation and percutaneous test stimulation of the sacral nerves at S3 and/or S4. All patients enrolled in the study had undergone prior conventional treatment, such as pharmacotherapy, hydrodistention and surgical intervention, which failed. All patients demonstrated a satisfactory response to trial stimulation and were randomly divided into a stimulation group (25 patients) and a control group (26). A sacral nerve stimulation device was implanted after 6 months in the control group. Patients were followed at 1, 3 and 6 months, and at 6-month intervals for up to 2 years after implantation of a neuroprosthetic InterStim* system. dagger The study variables included the number of voids daily, volume voided per void and degree of urgency before void. RESULTS: Compared to the control group, 6-month voiding diary results demonstrated statistically significant improvements (p <0.0001) in the stimulation group with respect to the number voids daily (16.9 +/- 9.7 to 9.3 +/- 5.1), volume per void (118 +/- 74 to 226 +/- 124 ml.) and degree of urgency (rank 2.2 +/- 0.6 to 1.6 +/- 0.9). Patients in the control group showed no significant changes in voiding parameters at 6 months. Significant improvements in favor of the stimulation group were noted in various parameters with respect to water cystometry and quality of life (SF-36). At 6 months after implant, neurostimulators were turned off in the stimulation group and urinary symptoms returned to baseline values. After reactivation of stimulation sustained efficacy was documented at 12 and 24 months. CONCLUSIONS: Neuromodulation of the sacral nerves is an effective, safe therapy that successfully treats significant symptoms of refractory urgency-frequency.

Adult↗

PubMed2001

[Neuromodulation and neurostimulation in urology].

Functional voiding disorders, such as urge incontinence and urine retention, have a high prevalence and often lead to stigmatisation and a diminished quality of life. Patients with idiopathic voiding dysfunctions, for whom conservative treatments are insufficient, can currently be treated with sacral neuromodulation. In sacral neuromodulation a pulse generator is implanted; it is a reversible treatment that can be tested beforehand to evaluate if the patient is eligible for it. After implantation a good result is obtained, on average, in 73% of patients. Patients with spinal cord injury may currently be treated with electrical neurostimulation of the anterior sacral roots, which results in the ability to void without a residue, evacuate stools and obtain an erection or vaginal lubrication. Over 80% of the implanted patients with a spinal cord injury void without residual urine. Furthermore, continence is restored and the bladder capacity increases. In patients with therapy-resistant functional micturition disorders and in patients with spinal cord injury, neuromodulation and neurostimulation must be considered before invasive surgery is carried out.

Electric Stimulation Therapy↗

PubMed2001

A pilot study of the home application of transcutaneous neuromodulation in children with urgency or urge incontinence.

PURPOSE: We evaluated the efficacy of transcutaneous neuromodulation to treat urinary urgency and urge incontinence in children with nonneurological bladder dysfunction. MATERIALS AND METHODS: Surface neuromodulation was delivered via skin electrodes away from the genital region for a short duration daily on a home treatment basis. Clinical outcome was measured by 3 tools previously tested for reliability including the frequency volume chart, urgency visual analog scale and accident diary ("Dry Pie"). RESULTS: After at least 1 month of application dryness had improved in 73.3% of children, mean urgency score had improved to equate action at urge as being 'easy to hold on' and there was a significant increase in mean voided volume. CONCLUSIONS: Initial evaluation of the home application of surface neuromodulation in children with urgency and/or urge incontinence revealed positive results and warrants a randomized controlled investigation. The finding that children were not completely dry with this treatment in isolation suggests that further study is needed to identify optimal treatment duration and stimulus intensity.

Child↗

PubMed1999

Sacral electrical neuromodulation as an alternative treatment option for lower urinary tract dysfunction.

Temporary electrical stimulation using anal or vaginal electrodes and an external pulse generator has been a treatment modality for urinary urge incontinence for nearly three decades. In 1981 Tanagho and Schmidt introduced chronic electrical stimulation of the sacral spinal nerves using a permanently implanted sacral foramen electrode and a battery powered pulse generator for treatment of different kinds of lower urinary tract dysfunction, refractory to conservative treatment. At our department chronic unilateral electrical stimulation of the S3 sacral spinal nerve has been used for treatment of vesi-courethral dysfunction in 43 patients with a mean postoperative follow up of 43,6 months. Lasting symptomatic improvement by more than 50 % could be achieved in 13 of 18 patients with motor urge incontinence (72,2 %) and in 18 of the 21 patients with urinary retention (85,7 %). Implants offer a sustained therapeutic effect to treatment responders, which is not achieved by temporary neuromodulation. Chronic neuromodulation should be predominantly considered in patients with urinary retention. Furthermore in patients with motor urge incontinence, refusing temporary techniques or in those requiring too much effort to achieve a sustained clinical effect. Despite high initial costs chronic sacral neuromodulation is an economically reasonable treatment option in the long run, when comparing it to the more invasive remaining therapeutic alternatives.

Journal Article↗

PubMed2003

[Treatment of urge incontinence by sacral neuromodulation in two patients with artificial sphincters].

Patients with stress urinary incontinence due to major sphincter incompetence are sometimes treated by artificial urinary sphincter (AUS). Some patients with AUS subsequently develop urge incontinence that is refractory, to pharmacological treatments. Sacral neuromodulation could constitute an alternative treatment in these cases. The authors report two patients treated by the combined use of these two implants with a follow-up of 24 months. The efficacy of sacral neuromodulation in this indication appears to be satisfactory. The presence of the AUS does not appear to modify the action of the neuromodulator.

Aged↗

PubMed2003

[Two indications for bilateral neuromodulation].

The authors report two cases of patients presenting with complex voiding disorders treated successfully by bilateral neuromodulation. In the first patient, bilateral neuromodulation (left S2 and right S3) was indicated after failure of a first trial of conventional neuromodulation. In the second case, a complementary electrode in addition to the S3 electrode was placed at S1 to treat nerve root pain associated with urinary symptoms. The preoperative and postoperative findings are reported together with the course and possible explanations for the success of this treatment modality.

Adult↗

PubMed2004

[Potential mechanisms of effects of endogenous neuromodulators on the interdependent activity of neurons in various nuclei of the basal ganglia].

A possible mechanism of influence of neuromodulators on interdependent activity of neurons in the diverse basal ganglia nuclei is suggested. According to modulation rules, an activation of postsynaptic Gs- or Gq/11-(Gi/0-) protein coupled receptors promotes induction of long-term potentiation (depression) of excitatory inputs to different neurons and augmentation (lowering) of their activity; an activation of presynaptic Gs- or Gq/11-(Gi/0-) protein coupled receptors promotes a rise (decrease) of release of GABA and co-peptides from striatal terminals and glutamate release from subthalamic terminals in the globus pallidus and output nuclei. It follows from the modulation rules that, since identical receptors are present on striatal neuron and their axon terminals, effects of neuromodulator action in diverse basal ganglia nuclei can be summarized. Neuromodulators released from striato-nigral and striato-pallidal fibers could promote interdependent activity of neurons in "direct" and "indirect" pathways through the basal ganglia due to convergence of these fibers on cholinergic interneurons and pallido-striatal cells.

Animals↗

PubMedDate not supplied

[Complex Regional Pain (CRPS) Syndrome type II. Timing for surgery and therapeutic options: neuromodulation].

OBJECTIVE: The object of this study is to evaluate the importance of a correct timing for surgery, the different strategies of therapy and the use of the neuromodulation in the Complex Regional Pain Syndrome (CRPS) type II. PATIENTS AND METHODS: The last 2 years we observed 8 patients with the clinical picture of a CPRS type II, due to previous peripheral nerve lesions of the upper extremity. All the patients followed a therapeutic protocol of neuromodulation and reconstructive surgical repair. RESULTS: Six patients out of eight had almost a complete recovery of the symptoms 6 months after the surgery. CONCLUSIONS: Our study demonstrates that the patients who underwent surgical repair followed by neuromodulation didn't present any recurrence of the symptoms.

Adult↗