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PubMed1990

Neuromodulation: associative and nonlinear adaptation.

Neuromodulation, the interaction between at least two chemical messengers in the nervous system, serves as a mechanism by which biochemical association can occur. A simple, yet compelling, hypothesis is that the criteria for expression of associative learning and memory are subserved by biochemical events which are also associative in nature. A neuromodulatory interaction that has been linked to memory function and which has been the subject of biochemical inquiry is the interaction between the catecholamine, norepinephrine (NE) and the neuropeptide, vasopressin (AVP). Studies described in this report show that vasopressin acts to potentiate norepinephrine (NE)-induced cyclic adenosine monophosphate (cAMP) accumulation in the hippocampus by a calcium-dependent mechanism. Results of these studies are considered in the context of the nonlinear properties of synergism and conditionality and in the context of the associative learning requirements of spatial and temporal coupling. Secondly, the calcium dependency of AVP-induced neuromodulation is considered in relation to the calcium dependency for induction of associative long-term potentiation. Lastly, the potential for changes in neuronal morphology in response to neuromodulatory events is considered. By using vasopressin potentiation of noradrenalin-induced cAMP formation as a model system, I have applied the theoretical framework of associative learning and memory to test the hypothesis that neuromodulation can serve as a biochemical analog of associative cognitive events.

Adaptation, Physiological↗

PubMed1992

Neuromodulation.

The ability of the nervous system to respond to the environment and to learn depends upon the tuning of neuronal electrical activity, loosely called neuromodulation. The substrates for electrical activity and, therefore, neuromodulation are ion channels which may be either synaptic or extrasynaptic. Neuromodulation is dynamic and most frequently involves neurotransmitters and hormones acting via G-protein-coupled pathways.

Animals↗

PubMed1995

Intrinsic and extrinsic neuromodulation of motor circuits.

Neuromodulation of motor circuits by extrinsic inputs provides enormous flexibility in the production of behavior. Recent work has shown that neurons intrinsic to central pattern-generating circuits can evoke neuromodulatory effects in addition to their neurotransmitting actions. Modulatory neurons often elicit a multitude of different effects attributable to actions at different receptors and/or through the release of co-transmitters. Differences in neuromodulation between species can account for differences in behavior. Modulation of neuromodulation may provide an additional level of flexibility to motor circuits.

Animals↗

PubMed2005

Sacral neuromodulation for the treatment of refractory urinary urge incontinence after stress incontinence surgery.

OBJECTIVE: This study was undertaken to evaluate the response to sacral neuromodulation in women with refractory, nonobstructive urinary urge incontinence after stress incontinence surgery. STUDY DESIGN: We reviewed the medical records of women in whom sacral neuromodulation was performed for worsening or de novo urinary urge incontinence after a stress incontinence procedure. All patients had undergone preliminary test stimulation. Demographics, surgical and urogynecologic history, including bladder diary and pad weight test, and urodynamic parameters were evaluated. RESULTS: Of 34 women, 22 (65%) responded to the test stimulation and underwent permanent lead implant. There was no difference between responders and nonresponders with respect to type of stress incontinence surgery. Incontinence or urodynamic parameters were not different between responders and nonresponders. Factors that were predictive of a positive response were women aged less than 55 years (P = .01), the test stimulation performed within 4 years of the stress incontinence procedure (P = .01), and evidence of pelvic floor muscle activity (P = .03). CONCLUSION: Sacral neuromodulation is a viable option for the treatment of refractory urinary urge incontinence that occurs after stress urinary incontinence surgery. Older women with no pelvic floor activity who are remote from their incontinence surgery may have a suboptimal response.

Electric Stimulation Therapy↗

PubMed2005

Complications and troubleshooting of sacral neuromodulation therapy.

As evident from the authors' series, the complications of sacral neuromodulation have changed with the introduction of the tined lead and the placement of the generator over the back. In the earlier series, most complications were related to pain at the generator site, which was rare in the authors' series. The posterior location of the generator seems to be better tolerated than the anterior location, which could explain the rare need for revisions for pain at the generator site. Lead migration was observed in 8.4% of the original sacral neuromodulation study group series. This was seen rarely in the authors' series in either stage-one or stage-two revisions. As part of the routine work-up of patients who present with decreased function after a successful period response in stage two, the authors obtain a lateral radiograph of the sacrum; the authors have made the diagnosis of lead migration rarely (1/130; 0.6%). Spinelli and colleagues reported on the use of the tined lead in 15 patients, and observed no lead migration during either the screening period (average 38.8 days) or during follow-up of IPG implantation cases (average 11 months). The total infection rate in the whole series was 18/180 (10%), which was slightly higher than that reported by the sacral neuromodulation study group (6.1%). Revision rates for stage one and stage two were 12.2% and 20%, respectively. The revision rate in the original study group was 33.3%. Thus, with advancing technology, new problems may arise, but the implanting physician should be aware of the ways to evaluate and manage these complications and appropriately troubleshoot patients with suboptimal responses.

Algorithms↗

PubMed2005

Sacral neuromodulation: long-term experience of one center.

OBJECTIVES: To perform a retrospective analysis of the long-term results of our experience with neuromodulation. Our center has been involved in the early studies leading to approval of the NeuroStim system of neuromodulation for the treatment of patients presenting with refractory lower urinary symptoms of urgency/frequency with or without incontinence and chronic urinary retention. METHODS: A total of 52 patients have undergone implantation at our center since 1990 using very rigid criteria, including temporary percutaneous nerve evaluation for up to 7 days and a requirement of 50% improvement before consideration for implantation. Patients were followed up closely and a telephone questionnaire was conducted for those patients not seen in the previous 6 months. Of the 52 patients, 11 were not available for evaluation. Of the 41 remaining patients, 22 had urgency/frequency syndrome, 6 had urgency incontinence, 9 had urinary retention, and 4 had interstitial cystitis with intractable pelvic pain. RESULTS: Of the 41 patients, 5 required explantation. These 5 patients were offered reimplantation but declined. Of the 22 patients in the urgency/frequency group, 10 (45%) had persistent improvement. In the urgency incontinence group, 3 of the 6 patients required explantation, and 1 (17%) reported improvement in the frequency of incontinence episodes. Of the 9 patients in the chronic urinary retention group, 7 (78%) had improvement. CONCLUSIONS: The long-term (up to 13 years) results of neuromodulation in patients presenting with urgency/frequency with and without urge incontinence and urinary retention were reviewed. The long-term results in the first two groups were not maintained over time. The patients with chronic urinary retention, although a small sample, fared better.

Adolescent↗

PubMed2005

Sacral neuromodulation for intractable urge incontinence: are there factors associated with cure?

OBJECTIVES: To determine the variables that affect the cure rate in patients with urge incontinence treated with sacral neuromodulation. METHODS: This prospective analysis of patients with refractory urinary urge incontinence who underwent placement of a neuromodulator lead and generator was undertaken between October 2000 and December 2003. Quantitative assessment of the severity of their urinary leakage was assessed by preoperative and postoperative 3-day bladder diaries documenting leakage episodes, number of pads used per day, and a 24-hour pad weight assessment. Cure was defined as no daily leakage episodes after permanent implantation. Subjective outcome was assessed using the Incontinence Impact Questionnaire. Two-sample independent t tests, two-way chi-square tests, and tests of two proportions were performed when appropriate, with P < 0.05 considered significant. RESULTS: The mean postimplantation follow-up was 29 months, and the average age was 60 years (range 29 to 83). The cure rate was associated with age, with individuals younger than 55 years having a statistically significant greater cure rate (65% versus 37% for older individuals; P < 0.05). Having three or more chronic conditions was associated with a lower cure rate in both younger and older individuals. Patients with a neurologic condition also had a lower cure rate, but no specific neurologic condition was associated. CONCLUSIONS: Age older than 55 years and more than three chronic conditions were independent factors associated with a lower cure rate in patients implanted with a sacral neuromodulator for refractory urge incontinence. A neurologic condition may be associated with a decrease in the cure rate.

Adult↗

PubMed2006

Complications and troubleshooting of two-stage sacral neuromodulation therapy: a single-institution experience.

OBJECTIVES: With the increasing use of sacral neuromodulation therapy, urologists are faced with postimplantation challenges. The purpose of this study was to identify these events and their causes and management in our large single-institution experience. METHODS: From July 2002 to September 2004, all patients who underwent sacral neuromodulation therapy for refractory bladder conditions were identified. Their medical records were retrospectively evaluated for history, operative intervention, and programming visits. Events after implantation of the implantable pulse generator (IPG) unit were noted. The evaluation, troubleshooting, management, and resolution of events at the last follow-up visit were extracted. RESULTS: A total of 214 patients underwent sacral neuromodulation therapy at our institution. The mean patient age was 53.5 +/- 15.4 years. Of the 214 patients, 161 underwent IPG implantation during a mean follow-up period of 16 months (range 5 to 30). The second-stage explantation and revision rate was 10.5% and 16.1%, respectively. The indications for explantation were infection (8 of 17) and failure to maintain a response (9 of 17). Revisions were done for decreases in response with abnormal (12 of 26) or normal (5 of 26) impedance measurements, IPG site discomfort (4 of 26), draining sinus at the IPG site (4 of 26), and lead migration (1 of 26). Equalization of impedance measurements was the most commonly observed impedance abnormality. These were managed by drying fluid from the connection in 4 patients and lead change in the rest. CONCLUSIONS: After IPG implantation, a decline in response may occur. Although some were explanted, most were revised, with most of the revisions functional on follow-up. Familiarity with impedance evaluation and development of algorithms for postimplant management are essential for troubleshooting and maintenance of the device.

Electric Stimulation Therapy↗

PubMed1998

Bilateral chronic sacral neuromodulation for treatment of lower urinary tract dysfunction.

PURPOSE: Chronic sacral neuromodulation aims at functional restoration of selected forms of nonneurogenic and neurogenic bladder dysfunction. The original technique, as described by Tanagho and Schmidt, provides unilateral sacral nerve stimulation via an implanted stimulator powering an electrode inserted into a sacral foramen. Its drawback was that the implant failed unpredictably in some patients despite previous successful percutaneous test stimulation. Therefore, we modified the stimulation technique to improve the efficacy of chronic sacral neuromodulation. MATERIALS AND METHODS: Guarded bipolar electrodes powered by an implantable neurostimulator were attached bilaterally directly to the S3 nerves through a sacral laminectomy in 9 women and 2 men (mean age 43.4 years). Of the patients 5 had urinary incontinence due to detrusor hyperactivity and 6 had urinary retention from detrusor hypocontractility. Mean followup with repeated urodynamics was 13 months (range 9 to 28). RESULTS: Four significant complications were encountered in 4 patients. In 10 patients the urological sequelae of the neurological disorder were alleviated significantly (50% or more), including 5 who experienced complete relief of symptoms. CONCLUSIONS: The efficacy of chronic sacral neuromodulation can be improved by bilateral attachment of electrodes directly to the sacral nerves.

Adult↗

PubMed2002

Unilateral versus bilateral sacral neuromodulation in patients with chronic voiding dysfunction.

PURPOSE: Bilateral sacral nerve neuromodulation has been proposed as a more effective treatment for chronic voiding dysfunction. However no comparison with the unilateral approach has been performed. We investigated the possible advantage of bilateral sacral neuromodulation. MATERIALS AND METHODS: In a prospective randomized crossover trial we investigated 33 patients who underwent bilateral implantation of a temporary test lead. Unilateral and bilateral test stimulation was continued for 4 to 6 days in all patients. Patients were randomly assigned to start with bilateral or unilateral stimulation. Between the stimulation episodes a 2-day washout interval was scheduled. Voiding diaries were completed at baseline and during the entire stimulation period. Sacral x-rays were taken to confirm lead positioning or possible migration after implantation and at the end of the test stimulation period. After 10 days the temporary leads were removed and voiding diaries were analyzed. RESULTS: After stimulation sacral x-ray revealed test lead migration in 8 patients, leaving 12 patients with urge incontinence and 13 with voiding difficulty and urinary retention available for review. A statistically significant improvement in voiding parameters was seen during the test stimulation period. However no statistically significant improvement was seen due to bilateral stimulation compared to unilateral stimulation. Two patients with urinary retention only started voiding to completion during bilateral stimulation. CONCLUSIONS: Bilateral is in general not superior to unilateral sacral neuromodulation. However, in some individuals bilateral stimulation may be more effective in relieving symptoms. Therefore, if unilateral percutaneous nerve evaluation fails, a bilateral test should be considered.

Adult↗

PubMed2002

Integrative neurocomputational perspectives on cognitive aging, neuromodulation, and representation.

Besides neuroanatomical changes, neuromodulatory mechanisms are also compromised during aging. Neural network models are suitable tools for exploring the relatively broad and homogenous neuromodulatory influences on cortical function. Computational approaches for understanding neuromodulation of the dynamic properties of cortical function and recent neurocomputational theories relating different aspects of cognitive aging with declines in neuromodulation are reviewed. Considered within an integrative cross-level neurocomputational framework, aging-related decline in dopaminergic neuromodulation reduces the fidelity of neural information and gives rise to less distinctive neural pattern representations that may underlie various facets of aging cognitive and, possibly also, sensorimotor phenomena.

Aging↗

PubMedDate not supplied

Instrumentation for neuromodulation.

The explosion in understanding how the central nervous system (CNS) works affords new opportunities to interact with the nervous system to compensate for dysfunction due to disease or injury. Neuromodulation is a term that describes methods that carry out that interaction based on principles of nerve cell physiology. There currently are two neuromodulation techniques used that require implantable devices-neurostimulation and implantable, chronic drug delivery. This article describes the devices used for neuromodulation, the motivation for the different feature sets of the devices, and the physiological and technological principles underpinning their use.

Electric Stimulation Therapy↗

PubMed2002

[Posterior sacral root neuromodulation in the treatment of chronic urinary dysfunction].

OBJECTIVES: To describe the effectiveness of sacral root neuromodulation in ameliorating symptoms of refractory voiding disfunction in our center. MATERIAL AND METHODS: During the period from december 1998 throught december 2001, 31 Percutaneous Nerve Evaluation (PNE) was performed to 20 patients with refractory voiding dysfunction; a sacral nerve stimulation device was implanted in 10 patients (8 female, 2 male). The median age was 49 years. Refractory voiding dysfunction included: mixed disorders (30%), idiopathic nonobstructive chronic urinary retention (20%), urgency/frequency (20%), faecal and urinary incontinence with absence of sphincter defect (20%) and frequency (10%). RESULTS: The 2 patients with frequency/urgency decreased their symptoms more than 50%, bladders were emptied without post-void residual urine in 2 patients with urinary retention, faecal and urinary incontinence in 2 patients and mixed disorders in other 3, reduced their symptoms more than 90% without residual urine. The frequency improved more than 50% in 1 patient. CONCLUSIONS: Sacral Root Neuromodulation is a successful treatment in some cases of idiopathic chronic micturition dysfunction which don't respond to pharmacotheraphy or bladder retraining. The effects of neuromodulation are long-lasting and associated morbidity is low.

Adolescent↗

PubMed2004

Developing a national continuous quality improvement system for neuromodulation treatment in The Netherlands.

BACKGROUND: Because neuromodulation was not included in the national health insurance system, the Dutch Neuromodulation Group (DNG) developed national standards and a continuous quality improvement (CQI) system for consistency in application of neuromodulation techniques and in the quality of outcomes. DEVELOPING THE NATIONAL QUALITY IMPROVEMENT SYSTEM: A stepwise approach was used in which the following ten steps were taken: (1) selected participating medical specialists and their centers, (2) described the treatment protocol, (3) collected data in a national database, (4) organized feedback sessions for the DNG, (5) formulated quality indicators, (6) adjusted the process of treatment, (7) formalized the structure of the DNG, (8) defined responsibilities, (9) established procedures for future development, and (10) made agreements with payers. DISCUSSION: Making reimbursement for expensive health care interventions contingent on a national CQI system created a powerful financial incentive to continuously provide effective care in an efficient manner.

Anesthesiology↗

PubMed2003

The role of neuromodulation in the management of urinary urge incontinence.

OBJECTIVE: To examine the benefit-risk profile of neuromodulation in treating refractory urinary urge incontinence and other voiding disorders. PATIENTS AND METHODS: The outcome measures from all patients in pivotal clinical trials who had undergone sacral nerve stimulation were analysed retrospectively. RESULTS: Neuromodulation was effective in several clinical studies; the response is durable and the benefit-risk profile good. CONCLUSION: Sacral nerve stimulation is becoming the standard of care for refractory overactive bladder and retention problems. The potential benefit of neuromodulation should be included in female urology and gynaecology training programmes.

Adolescent↗

PubMed2003

[Sacral neuromodulation in patients with nonobstructive, chronic urinary retention: relevance of the carbachol test and influence of associated nerve lession].

OBJECTIVE: Aim of this study was to evaluate whether the carbachol test and the nerve lesions responsible for bladder dysfunction possess predictive value in patients with chronic urinary retention who undergo temporary sacral neuromodulation (PNE test). MATERIAL AND METHODS: In 1999 and 2000, PNE tests were performed in 24 patients with chronic urinary retention and acontractile detrusor previously assessed by urodynamics. In 18 patients, a carbachol test was performed during urodynamics. The diagnosis related to the acontractile detrusor was additionally assessed and compared to the successful outcome of the PNE test. RESULTS: The PNE test was successful in 8 of the 24 patients (33.3 %). The bladder was completely emptied during the PNE test in 3 of the 10 patients with negative carbachol test and in 3 of the 8 patients with positive carbachol test. The highest success rate (80 %) was observed in patients after hysterectomy, whereas after lumbosacral pulposal prolapse or with a CNS tumor, it was only 20 - 33.3 %. CONCLUSIONS: We conclude that sacral neuromodulation is an effective treatment option in patients with nonobstructive urinary retention. The carbachol test does not possess any definitive predictive value with respect to the success rate of sacral neuromodulation in patients with chronic urinary retention. The success rate more likely depends on the localisation of the nerve lesion. PNE tests should be performed in all patients with therapy resistent nonobstructive urinary retention, as no other predictive factors exist.

Adult↗

PubMed1989

Noise in neural networks: thresholds, hysteresis, and neuromodulation of signal-to-noise.

We study a neural-network model including Gaussian noise, higher-order neuronal interactions, and neuromodulation. For a first-order network, there is a threshold in the noise level (phase transition) above which the network displays only disorganized behavior and critical slowing down near the noise threshold. The network can tolerate more noise if it has higher-order feedback interactions, which also lead to hysteresis and multistability in the network dynamics. The signal-to-noise ratio can be adjusted in a biological neural network by neuromodulators such as norepinephrine. Comparisons are made to experimental results and further investigations are suggested to test the effects of hysteresis and neuromodulation in pattern recognition and learning. We propose that norepinephrine may "quench" the neural patterns of activity to enhance the ability to learn details.

Animals↗

PubMed2006

Muscle fibrillation as a sign of electrode damage in sacral neuromodulation.

Sacral root neuromodulation is recognized as an effective therapy for chronic voiding dysfunction. However, knowledge about the neuromodulator in the general medical community is scarce. We report a case of muscle fibrillation caused by current leaking from a neuromodulator lead which had been damaged during disc prolapse surgery.

Adult↗