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PubMed1998

Computational models of neuromodulation.

Computational modeling of neural substrates provides an excellent theoretical framework for the understanding of the computational roles of neuromodulation. In this review, we illustrate, with a large number of modeling studies, the specific computations performed by neuromodulation in the context of various neural models of invertebrate and vertebrate preparations. We base our characterization of neuromodulations on their computational and functional roles rather than on anatomical or chemical criteria. We review the main framework in which neuromodulation has been studied theoretically (central pattern generation and oscillations, sensory processing, memory and information integration). Finally, we present a detailed mathematical overview of how neuromodulation has been implemented at the single cell and network levels in modeling studies. Overall, neuromodulation is found to increase and control computational complexity.

Animals↗

PubMed2006

The current use of neuromodulation for bladder dysfunction.

Neuromodulation utilizes electrical stimulation to alter the function of an organ. Recent advances in technology and improved knowledge of micturition physiology have coincided with the growth of neuromodulation for the treatment of urinary urgency/frequency, urge incontinence and non-obstructive urinary retention. Currently, the most common modality for bladder neuromodulation involves stimulation through the S3 foramen, or sacral neuromodulation. This review will highlight the current indications, patients selection, implantation options/techniques, outcomes and complications of sacral neuromodulation. In addition, other methods of neuromodulation will be discussed.

Electric Stimulation Therapy↗

PubMed2007

Management of refractory urinary urge incontinence following urogynecological surgery with sacral neuromodulation.

AIMS: We sought to explore our patient outcomes utilizing sacral neuromodulation in the management of refractory urinary urge incontinence following urogynecological surgical procedures. METHODS: A total of 25 women with urinary urge incontinence following urogynecological surgery were selected for SNS therapy and retrospectively analyzed. All patients completed a comprehensive urological evaluation. Clinical data was recorded to determine outcomes and identify parameters that would be predictive of response to neuromodulation. Outcomes were determined via subjective patient questionnaire and graded as follows: significant response (> or =80% improvement), moderate response (> or =50% and <80% improvement), and poor response (<50% response). RESULTS: Nineteen patients had a previous pubovaginal sling (10 with concomitant pelvic prolapse repair), 3 a previous retropubic suspension, and 3 a transperitoneal vesicovaginal fistula repair. Urethrolysis was performed in 4 patients to alleviate bladder outlet obstruction prior to sacral neuromodulation. Mean patient age was 59.8 years and length of follow-up was 7.2 months. Twenty-two women (88%) had the IPG placed during a Stage 2 procedure. Twenty patients maintained at least a 50% improvement in clinical symptoms at last follow-up and 6 patients were continent. Overall, the number of pads/day improved from 4.2 to 1.1 (P < 0.001). There were no significant differences in response to neuromodulation based upon age, duration of symptoms, type of surgery, or urodynamic parameters. CONCLUSION: Sacral neuromodulation appears to be an effective therapy in patients with refractory urge incontinence following urogynecological surgery. Larger prospective studies with longer follow-up are needed to assess the durability of this therapeutic modality.

Adult↗

PubMed1999

Sacral root neuromodulation in the treatment of various voiding and storage problems.

This paper reviews the use of sacral neuromodulation as a treatment modality for patients with bladder dysfunction. The dual functions of the urinary bladder are to act as a reservoir and to evacuate under voluntary control. Bladder dysfunction is a descriptive term describing the loss or the impairment of one or both of these functions. In the first part of the manuscript we describe the different components of sacral neuromodulation: the screening test known as percutaneous nerve evaluation (PNE), which involves screening patients who could potentially benefit from the therapy. Those who show a satisfactory response will have a permanent neuroprosthesis implanted. The technical aspects of both components of neuromodulation are described in detail, as well as the technical difficulties encountered. In the second part we present our long-term results in patients with sacral neuromodulation. Sacral neuromodulation is a safe and efficient therapeutic modality that helps patients with refractory voiding dysfunction restore their bladder function.

Electric Stimulation Therapy↗

PubMed2005

Prolonged sacral neuromodulation testing using permanent leads: a more reliable patient selection method?

OBJECTIVE: To assess the effect of prolonged sacral neuromodulation testing using permanent leads comparing the usual evaluation period of 4 to 7 days to a prolonged evaluation period of a minimum of 14 days. PATIENTS AND METHODS: A consecutive series of 20 patients (16 females and 4 males) undergoing prolonged sacral neuromodulation testing using permanent leads between September 2000 and March 2004 were evaluated retrospectively. 10 suffered from urgency-frequency syndrome, 3 from urge incontinence and 7 from non-obstructive chronic urinary retention. Key bladder diary variables at baseline, after the usual and prolonged evaluation period and at the last follow-up were compared. RESULTS: The median age was 52 years (interquartile range (IQR) 38-59) and the median evaluation period 28 days (IQR 18-29). 16 of the 20 patients (80%) had successful prolonged sacral neuromodulation testing and underwent the implantation of the IPG that was placed in the anterior abdominal wall in 6 and in the upper buttock in 10 patients. The eligibility for IPG implantation was significantly (p=0.031) increased from 50% after the usual to 80% after the prolonged evaluation period. At a median follow-up of 22 months (IQR 12-34), sacral neuromodulation was successful in 14 (88%) of the 16 IPG implanted patients but failed in 2. CONCLUSIONS: Prolonged sacral neuromodulation testing using permanent leads is more reliable for accurate patient selection than the usual evaluation period. Therefore, this method is strongly recommended and suggested to become the standard test procedure.

Abdominal Wall↗

PubMed2002

Alterations of cortical electrical activity in patients with sacral neuromodulator.

OBJECTIVES: Sacral neuromodulation represents chronic stimulation of the sacral (S3) nerve. So far, the mode of action and neuro-anatomical basis is unclear. Sacral reflex mechanisms as well as pontine or cortical centers of modulation have been postulated. Our aim was to evaluate possible alterations in electroencephalogram (EEG) activity as an indicator of a supraspinally mediated mechanism of sacral neuromodulation. MATERIALS AND METHODS: We analyzed serial EEGs (apparatus: Kölner Vitaport System) using electrodes placed at Fz, Cz, Cz' and Pz in 10 patients. Subsequently, the sacral (S3) nerve was stimulated by means of an impulse generator (Medtronic, Interstim 3023) using an on-off paradigm with a 1.5s "on" interval followed by a 10s stimulation break. Raw data were analyzed using both Matlab 4.0 software and a specially developed averaging routine. RESULTS: All patients demonstrated a cortical potential complex following sacral root stimulation with an early electronegative component at 50 ms with a mean amplitude of 23 microV followed by a late potential component with a mean latency of 253 ms and a mean amplitude of 5 microV, both with a maximum at Cz, corresponding to the post-central gyrus. This finding occurred irrespective of patient's reports of actually feeling the neuromodulator being switched on and off. CONCLUSION: In neuromodulation responders, both short and long latency cortical potentials can be reproduced with a maximum at the sensory cortical area. Although these potentials are similar to cognitively mediated "event-related potentials", they are clearly distinct from any subjective sensory or even painful response since several patients of this series have not been able to feel any neuromodulator action. Therefore, this pilot study indicates a supraspinally mediated site of modulation, most probably in sensory cortex areas.

Adult↗

PubMed1997

The urodynamic evaluation of neuromodulation in patients with voiding dysfunction.

OBJECTIVES: To determine which patients with voiding dysfunction might be suitable for treatment with neuromodulation, using urodynamics to obtain an objective measure of improvement and to illustrate the effect of neuromodulation on voiding dysfunction. PATIENTS AND METHODS: Patients were selected for implantation of a neuroprosthesis using a urodynamic evaluation before and during subchronic stimulation; 27 such patients (four men and 23 women, mean age 33 years, SD 15) were evaluated. RESULTS: Of the 27 patients, the 17 who responded well to neuromodulation all had hypocontractile detrusors and sphincter hypertonicity; sphincter relaxation during micturition was impaired. The urodynamic evaluation showed that these patients were not obstructed. Of 10 patients with spastic pelvic floor syndrome, nine responded well to the treatment. Those not responding to neuromodulation had mainly acontractile detrusors. CONCLUSION: The ideal candidates for neuromodulation are those patients with a spastic pelvic floor syndrome or with a hypocontractile detrusor, in combination with sphincter instability, and impaired sphincter relaxation. An increase of bladder contractility, enhancement of sphincter relaxation and decrease in bladder capacity and residual urine are the most important features of the response.

Adult↗

PubMed2001

Computerized assessment of detrusor instability in patients treated with sacral neuromodulation.

PURPOSE: We previously described an automatic procedure for diagnosing and grading detrusor instability using a cystometric study. In our current study we applied a modified version of the program in patients with urge incontinence treated with sacral neuromodulation to test its capacity to detect changes after therapeutic intervention and understand the mode of action of neuromodulation. MATERIALS AND METHODS: We analyzed cystometric studies before and after neuromodulation in 26 consecutive patients, including 22 women and 4 men, and evaluated parameter changes. We also assessed the relationship of instability parameters at baseline with symptomatic results, which were derived from voiding-incontinence diaries, in female patients to identify urodynamic prognosticators of success. RESULTS: The automatic procedure correctly diagnosed stability and instability in our patients in 51 of the 52 measurements considered. Neuromodulation had an average suppressive effect on the amplitude of unstable contractions. At baseline the amplitude of the maximum unstable contraction and mean active pressure during unstable episodes were significantly less in the 7 women who achieved stability than in the 15 who did not. However, no urodynamic parameters were identified that predicted the symptomatic outcome of treatment. CONCLUSIONS: Our algorithm accurately diagnoses and grades detrusor instability, and provides parameters with predictive value in regard to the probability that a bladder may or may not become stable with neuromodulation. However, the symptomatic result of this treatment option seems to depend on noncystometric factors.

Algorithms↗

PubMed2005

Changes in brain activity following sacral neuromodulation for urinary retention.

PURPOSE: Sacral nerve stimulation (neuromodulation) can restore bladder sensation and the ability to void in women with urinary retention due to sphincter overactivity (Fowler's syndrome). Modulation of central afferent activity is considered critical to this therapeutic effect but the neural mechanisms are poorly understood. Therefore, we undertook a functional brain imaging study to determine how neuromodulation acts on brain centers involved in the representation and control of bladder function. MATERIALS AND METHODS: Eight patients with Fowler's syndrome and 8 healthy controls underwent brain imaging with positron emission tomography to identify regions of brain activity relating to the perception of bladder fullness and their modulation by sacral nerve stimulation. RESULTS: In healthy controls bladder fullness enhanced activity in brainstem (midbrain) and limbic cortical regions. Women with urinary retention showed no significant brainstem activity but did show enhanced limbic cortical activity when the bladder was full in the absence of neuromodulation. Neuromodulation restored a normal pattern of midbrain activity and decreased cortical activity in this group. CONCLUSIONS: Our study provides novel neuroimaging evidence for the existence of abnormal interaction between brainstem and cortical centers in women with urinary retention. Furthermore, we have been able to show evidence that the therapeutic effect of sacral neuromodulation is achieved through restoration of activity associated with brainstem autoregulation and attenuation of cingulate activity.

Adult↗

PubMed2004

A rat model for studying effects of sacral neuromodulation on the contractile activity of a chronically inflamed bladder.

OBJECTIVE: To develop an animal model in which the effects of electrical stimulation of the sacral nerves (sacral neuromodulation) on a chronic hyperactive urinary bladder can be studied. MATERIALS AND METHODS: In female rats the urinary bladder was instilled with mustard oil (0.4%); after 10 days the animals were anaesthetized with intraperitoneal urethane, the bladder catheterized and connected to a pressure transducer. Stimulating electrodes were placed into the sacral foramina bilaterally. The intensity and duration of sacral electrical stimulation was varied systematically to determine the effects of the sacral neuromodulation on bladder contractions. RESULTS: The main effect of the neuromodulation was an increase in the interval between contractions, i.e. during and for some time after the stimulation the contractions were completely abolished. The duration of the pause increased with the intensity and duration of stimulation. After the contractions had reappeared the frequency of contractions was reduced for a long period. In animals with chronic cystitis the effects of neuromodulation tended to be stronger (the pauses were longer) than in control animals with an intact bladder, but only in one test (increase of pause length with stimulus duration) was the difference statistically significant. CONCLUSIONS: The results show that this animal model is suitable for studying the effects and mechanisms of sacral neuromodulation on a chronic hyperactive urinary bladder.

Animals↗

PubMed1999

Neuromodulation by implant for treating lower urinary tract symptoms and dysfunction.

OBJECTIVE: Patients with irritative micturition complaints, pelvic pain, involuntary urine loss or urinary retention are sometimes difficult to treat. The advent of direct sacral nerve stimulation offers a therapeutic alternative if conservative measures fail and surgery is considered. This paper reviews therapeutic neuromodulation by implant for treating lower urinary tract symptoms and dysfunction. METHODS: The international literature is reviewed on topics such as the physiological basis of neuromodulation, techniques of acute testing and chronic implantation, and clinical results. Future developments and ways for possible improvement are discussed. RESULTS: The mode of action of neuromodulation is probably through restoring the correct balance between excitatory and inhibitory impulses from and to the pelvic organs at a sacral and supra-sacral level. Depending on the predefined success criteria, average success rates of definitive implants vary from 50 to 70%. From the data it seems that patients with urge incontinence and urinary retention are the best candidates for neuromodulation. In the literature the lack of standardisation of selection criteria, stimulation parameters and definitions of success is striking. CONCLUSIONS: Neuromodulation by implant is a useful therapeutic alternative. It should at least be considered in patients with therapy-resistant urge incontinence and urinary retention before proceeding to surgery. Issues such as underlying physiology, methodological standardisation, technical improvements, and patient selection must be addressed in future research.

Animals↗

PubMedDate not supplied

[Temporary sacral neuromodulation in patients with urge incontinence].

We studied the effect of temporary sacral (S3) nerve stimulation in patients with urge incontinence (UI) who were subjected to percutaneous nerve evaluation of the S3 roots as a temporary screening test during 12 days to determine response to neuromodulation. All 18 patients (14 women and 4 men) underwent S3 neuromodulation. The response was assessed by a detailed voiding diary, symptom score and objective outcome was analyzed with urodynamic studies. We noticed a decrease of the average voiding frequency, the number of leakage episodes and pads use per 24 h in 10 days of S3 neuromodulation and returning to baseline symptoms in 20 days after completing S3 neuromodulation. Cystometrograms demonstrated increased cystometric capacity and decreased frequency and amplitude of unstable contractions. Correlation between symptomatic and urodynamic effects was incomplete. Temporary S3 neuromodulation relieved symptoms in UI patients.

Adult↗

PubMedDate not supplied

[A possible mechanism of the influence of neuromodulators and modifiable inhibition on long-term potentiation and long-term depression of excitatory inputs to main hippocampal neurons].

A hypothetic mechanism explaining the influence of various neuromodulators and modifiable disynaptic inhibition on the long-term potentiation and depression (LTP and LTD) of excitatory inputs to granule and pyramidal hippocampal cells is proposed. According to this mechanism, facilitation of the LTD/LTP of excitatory inputs to an inhibitory interneuron caused by the action of a neuromodulator on a receptor bound with Gi/0/(Gs or Gq/11) protein can reduce/augment the GABA release, weaken/intensify the target cell inhibition, and promote the induction of the LTP/LTD of excitatory inputs to this cell. In the absence of the inhibition, the same neuromodulator would promote the LTD/LTP induction in the target cell by activating the same receptor types. The resulting effect of a neuromodulator on a target cell depends on the ratio between the "strengths" of its excitatory and inhibitory inputs, on the presence of receptors of the same or different types at the interneuron and the target cell, and on the neuromodulator concentration due to its different affinity for receptors, interaction with which provide its influence on postsynaptic processes in opposite directions. The consequences of suggested mechanism are in agreement with the known experimental data.

Animals↗

PubMed2001

Quality of life assessment in patients who undergo sacral neuromodulation implantation for urge incontinence: an additional tool for evaluating outcome.

PURPOSE: We investigated the impact of sacral neuromodulation on quality of life and assessed the importance of quality of life for determining the success of sacral neuromodulation in patients with detrusor hyperactivity, including instability and hyperreflexia. We also compared it with parameters documented in a voiding diary. MATERIALS AND METHODS: From May 1998 to December 2000, 82 female and 31 male patients 17 to 79 years old (mean age 51.1) with urge incontinence (63), urgency/frequency (5), voiding disturbance (41) and pelvic pain (4) resistant to conservative treatment were enrolled in a national prospective registry after showing a positive response to percutaneous nerve evaluation testing. Of the patients 47 who were 32 to 79 years old (mean age 59.2) with urge incontinence due to detrusor instability and 16 who were 27 to 51 years old (mean age 51.5) with hyperreflexia were asked to complete a validated self-reporting incontinence domain specific quality of life questionnaire before, and 3, 6, 9, 12, 18, 24 and 36 months after implantation. RESULTS: Compared with baseline the quality of life index significantly improved at each followup, which strongly correlated with the decrease in the number of incontinence episodes. CONCLUSIONS: Evaluating quality of life may be an additional useful tool for assessing the results of sacral neuromodulation for urge incontinence. Our study confirms that sacral neuromodulation is effective therapy for urge incontinence that can have a positive effect on patient quality of life.

Adolescent↗

PubMed2003

Measuring the sensations of urge and bladder filling during cystometry in urge incontinence and the effects of neuromodulation.

AIMS: As urge and urgency contribute greatly to a patient's symptoms, it follows that sensory evaluation combined with noninvasive neuromodulation during urodynamics may provide new criteria for improving patient selection for an implantable stimulator. The purpose of this research was to develop and validate an objective measure of bladder sensations during filling cystometry and then to apply this technique to evaluate the effects of neuromodulation on the sensations of urge measured in this way. METHODS: In study 1 a new patient-activated keypad device was tested during urodynamics to measure bladder sensations according to a 0-4 scale and validated by using a technique adapted from a standard psychophysical sensory threshold testing method. In study 2 the effects of pudendal afferent nerve stimulation on measured sensations of urge were assessed during cystometry with patients as their own controls. Forty-three patients diagnosed with idiopathic detrusor instability were studied; 10 participated in study 1 and 35 in study 2. RESULTS: The new device gave reliable and repeatable measures of sensations with statistically significant differences in bladder volume at each of the urge levels tested (Wilcoxon matched pairs test). Neuromodulation suppressed urinary urge in 89% of the 35 patients. This effect was associated with a statistically significant increase in bladder volume at all urge levels. CONCLUSIONS: A new patient operated key-pad device provided a reliably objective measure of sensations of urge during urodynamics without the need for prompting. Neuromodulation using noninvasive pudendal afferent stimulation suppressed these sensations whilst increasing bladder volume.

Electric Stimulation Therapy↗

PubMed2004

A review of non-invasive electro neuromodulation as an intervention for non-neurogenic bladder dysfunction in children.

AIMS: The use of electrotherapeutics to improve filling and emptying dysfunction of the adult bladder has been well established, however the practice in children is less well known. The purpose of this review is to summarize the rationale behind the use of electro neuromodulation in children, examine the reported efficacy of the intervention for different presentations of dysfunction, and establish the current limitations to knowledge and practice. MATERIALS AND METHODS: A modified systematic review was carried out on all Medline studies identified as considering the use of electrotherapy or neuromodulation in children with bladder problems. Literature relating to use of this approach in adults was also searched in order to present current understanding of the treatment rationale and modes of application. RESULTS: A Medline search and handsearch of relevant conference proceedings revealed six studies of neuromodulation in children with non-neurogenic bladder dysfunction. There were no reports of the intervention in children with isolated pelvic floor dyssynergia, irritative symptoms, structural changes predisposing the pelvic floor to weakness, or monosymptomatic nocturnal enuresis. One report of the favorable effect of neuromodulation on gut dysmotility was identified. Study design and quality generated level 4 evidence. Positive post-intervention changes reported included: increased bladder capacity, decreased severity of urge, improved continence, and decrease frequency of urinary tract infection. Significant improvement in the urodynamic parameters of bladder compliance, number of uninhibited contractions, and bladder volume at first detrusor contraction were also reported. CONCLUSIONS: There are clear benefits from the use of electroneuromodulation in children with differing forms of voiding dysfunction. The treatment approach is independent of cognitive and pharmacological therapy, is minimally invasive, and free of side effects. To date, there are no clinical variables that reliably predict efficacy of electrotherapy in the various presentations of over and under active detrusor, sphincter dyssynergia, or irritative symptoms.

Child, Preschool↗

PubMed2006

Sacral neuromodulation and lower urinary tract dysfunction in cerebral palsy.

Given the emerging role of sacral neuromodulation in treatment of neurogenic voiding dysfunction, the author describes the use of sacral neuromodulation in a patient with voiding dysfunction caused by cerebral palsy (CP). A 45-year-old patient with cerebral palsy presented with progressive complaints of urgency and overflow incontinence and was found to be in retention. She underwent sacral neuromodulation and had complete resolution of her symptoms. The literature of lower urinary tract dysfunction in CP is reviewed. It is concluded that sacral neuromodulation may be a valuable tool in treating storage and voiding disorders associated with CP.

Cerebral Palsy↗

PubMed2003

Minimally invasive sacral neuromodulation implant technique: modifications to the conventional procedure.

PURPOSE: Sacral neuromodulation is a novel treatment for selected urinary and bowel dysfunctions. A new method is described for electrode implantation, the "minimally invasive sacral neuromodulation implant technique." METHODS: After the percutaneous nerve evaluation test, a small longitudinal incision (3 cm) is made, and a catheter cannula segment is inserted through the sacral foramen beside an insulated needle. The electrode is introduced into the catheter cannula, which is then removed and fixed to the sacrum by means of small anchors. The proximal part of the lead is tunneled into the subcutaneous tissue, reaching the pocket made to accommodate the neurostimulator. RESULTS: This procedure was performed in ten patients (5 male; mean age, 50.4 years). In four patients a single electrode was implanted, and in six patients two electrodes were implanted. The minimally invasive technique was significantly faster, saving a mean time of 20 minutes for each electrode. The incision made directly on the sacral foramen was significantly reduced (3 vs. 12 cm), avoiding the wide, blunt dissection of subcutaneous fat tissue. Application of the catheter cannula allowed the electrode to be introduced easily and correctly. The electrode anchors never failed: no cases of lead displacement or suboptimal position of the electrode occurred. A unilateral, sterile subcutaneous seroma occurred in one of the ten patients. CONCLUSIONS: The minimally invasive sacral neuromodulation implant technique seems to be a safe procedure-making sacral neuromodulation implant easier, faster, and safer, in as much as complications could be potentially reduced.

Constipation↗