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.     

Electrical stimulation for the treatment of bladder dysfunction: current status and future possibilities

Electrical stimulation of peripheral nerves can be used to cause muscle contraction, to activate reflexes, and to modulate some functions of the central nervous system (neuromodulation). If applied to the spinal cord or nerves controlling the lower urinary tract, electrical stimulation can produce bladder or sphincter contraction, produce micturition, and can be applied as a medical treatment in cases of incontinence and urinary retention. This article first reviews the history of electrical stimulation applied for treatment of bladder dysfunction and then focuses on the implantable Finetech-Brindley stimulator to produce bladder emptying, and on external and implantable neuromodulation systems for treatment of incontinence. We conclude by summarizing some recent research efforts including: (a) combined sacral posterior and anterior sacral root stimulator implant (SPARSI), (b) selective stimulation of nerve fibers for selective detrusor activation by sacral ventral root stimulation, (c) microstimulation of the spinal cord, and (d) a newly proposed closed-loop bladder neuroprosthesis to treat incontinence caused by bladder overactivity.     

The role of electrical neuromodulation in the therapy of chronic lower urinary tract dysfunction

The electrostimulation techniques may be used as a supplement or an alternative to standard therapy. Electrical therapy for chronic lower tract dysfunction comprises of non-invasive pudendal nerve neuromodulation and invasive sacral nerve stimulation. Short-term functional electrical stimulation seems favourable in selected patients with detrusor hyperreflexia. Sacral nerve stimulation may be a successful treatment option for patients with refractory detrusor overactivity and some forms of urinary retention.     

Sacral Nerve Stimulation for Treatment of Intractable Pain Associated with Cauda Equina Syndrome

Sacral nerve stimulation (SNS) is an effective treatment for bladder and bowel dysfunction, and also has a role in the treatment of chronic pelvic pain. We report two cases of intractable pain associated with cauda equina syndrome (CES) that were treated successfully by SNS. The first patient suffered from intractable pelvic pain with urinary incontinence and fecal incontinence after surgery for a herniated lumbar disc. The second patient underwent surgery for treatment of a burst fracture and developed intractable pelvic area pain, right leg pain, excessive urinary frequency, urinary incontinence, voiding difficulty and constipation one year after surgery. A SNS trial was performed on both patients. Both patients'' pain was significantly improved and urinary symptoms were much relieved. Neuromodulation of the sacral nerves is an effective treatment for idiopathic urinary frequency, urgency, and urge incontinence. Sacral neuromodulation has also been used to control various forms of pelvic pain. Although the mechanism of action of neuromodulation remains unexplained, numerous clinical success reports suggest that it is a therapy with efficacy and durability. From the results of our research, we believe that SNS can be a safe and effective option for the treatment of intractable pelvic pain with incomplete CES.     

Sacral Nerve Root Stimulation for the Treatment of Urge Incontinence and Detrusor Dysfunction Utilizing a Cephalocaudal Intraspinal Method of Lead Insertion: A Case Report

Sacral nerve root stimulation (SNRS) is known to be effective in the treatment of pelvic motor dysfunction( 1 - 4 ). Bladder and urethral motor disorders commonly treated include urinary urge incontinence, voiding/detrusor dysfunction, and urgency/frequency syndromes. To date, neurostimulation specific to bladder and urethral dysfunction has applied a unilateral, trans‐sacral approach. (Interstim, Medtronic, Minneapolis, MN) Despite some success, this method has been associated with technical failures in maintaining electrode position( 5 , 6 ). As an alternative, this case report describes the selective epidural application of a cephalocaudal (“retrograde”) lead insertion method in a patient with severe detrusor dysfunction and urinary urge incontinence( 7 ).     

Existing and emerging applications for the neuromodulation of nerve activity through targeted delivery of electric stimuli

Abstract

The effective treatment of many diseases requires the use of multiple treatment strategies among which neuromodulation is playing an increasingly important role. Neuromodulation devices that act to normalize or modulate nerve activity through the targeted delivery of electrical stimuli will be the focus of this review. These devices encompass deep brain stimulators, vagus nerve stimulators, spinal cord simulators and sacral nerve stimulators. Already neuromodulation has proven successful in the treatment of a broad range of conditions from Parkinson’s disease to chronic pain and urinary incontinence. Many of these approaches seek to exploit the activities of the autonomic nervous system, which influences organ function through the release of neurotransmitters and associated signalling cascades. This review will outline existing and emerging applications for each of these neuromodulation devices, proposed mechanisms of action and clinical studies evaluating both their safety and therapeutic efficacy.     

Temporary sacral and tibial neuromodulation in treating patients with overactive urinary bladder

The effects of temporary sacral (S3) stimulation and posterior tibial nerve stimulation were studied in patients with the overactive urinary bladder. Unilateral temporal (10 days) electrical stimulation of the S3 sacral spinal nerve (32 patients) and posterior tibial nerve stimulation (18 patients) were used to treat this abnormality. There was a decrease in the average frequency of voiding, in the number of leakage episodes and used pads per day after both stimulations. An over 50% symptomatic improvement was achieved in 19 of the 32 patients and after temporary sacral (S3) stimulation and in 14 of the patients following posterior tibial nerve stimulation. Neuromodulation is an effective treatment in patients with the overactive bladder.     

Cortical,Spinal, Sacral,and Peripheral Neuromodulations as Therapeutic Approaches for the Treatment of Lower Urinary Tract Symptoms in Multiple Sclerosis Patients: A Review

IntroductionMultiple sclerosis (MS) is often associated with urological disorders, mainly urinary incontinence and retention, the management of which being necessary to improve patient's quality of life (QOL) and to reduce potential urological complications. Besides the classical treatments based mainly on anticholinergics and/or self-catheterization, several neuromodulation techniques have been tried in recent years to improve these urinary disorders. By this review, we aim at providing an overview of neuromodulation and electrostimulation approaches to manage urinary symptoms in MS patients.Materials and MethodsA literature search using MEDLINE was performed. Only papers in English, and describing the effects of neuromodulation in MS patients, were considered.ResultsA total of 18 studies met inclusion criteria and were reviewed. Of them, four related to sacral neuromodulation (SNM), seven to percutaneous tibial nerve stimulation (PTNS), six to spinal cord stimulation (SCS), and one to transcranial magnetic stimulation (TMS).DiscussionPTNS and SNM seem to be effective and safe therapeutic options for treating lower urinary tract symptoms in MS patients principally in case of overactive bladder (OAB) symptoms. Similarly, also SCS and TMS have been shown to be effective, despite the very limited number of patients and the small number of studies found in the literature. Interestingly, these techniques are effective even in patients who do not respond well to conservative therapies, such as anticholinergics. Furthermore, given their safety and efficacy, stimulations such as PTNS could be considered as a first-line treatment for OAB in MS patients, also considering that they are often preferred by patients to other commonly used treatments.     

Principles of Sacral Nerve Stimulation (SNS) for the Treatment of Bladder and Urethral Sphincter Dysfunctions

Objectives. Sacral nerve stimulation (SNS) (Medtronic, Inc., Minneapolis, MN) is an exciting new treatment for refractory voiding disorders including urinary incontinence, retention, and voiding dysfunction. It is known that both voiding and continence reflex mechanisms are organized in the sacral spinal cord and that pathologic conditions can alter the balance between these two opposing mechanisms. Methods. The background and surgical technique of SNS will be presented. This will be followed by a discussion of hypotheses on how SNS works. Results. The beneficial effects of SNS are most reasonably attributed to activation of somatic afferent axons in the sacral spinal roots. This evoked afferent activity in turn modulates sensory processing and micturition reflex pathways in the spinal cord. Hyperactive voiding can be suppressed by direct inhibition of bladder preganglionic neurons as well as inhibition of interneuroneal transmission in the afferent limb of the micturition reflex. On the other hand, voiding in patients with urinary retention can be facilitated by inhibition of reflex pathways to the urethral outlet (guarding reflexes). Conclusions. SNS, a nonablative, minimally invasive technique for urologists, holds great promise for a large number of patients who suffer debilitating and refractory urinary symptoms.     

Sacral Neuromodulation for Lower Urinary Tract and Bowel Dysfunction in Animal Models: A Systematic Review With Focus on Stimulation Parameter Selection

ObjectiveConventional sacral neuromodulation (SNM) has shown to be an effective treatment for lower urinary tract and bowel dysfunction, but improvements of clinical outcome are still feasible. Currently, in preclinical research, new stimulation parameters are being investigated to achieve better and longer effects. This systematic review summarizes the status of SNM stimulation parameters and its effect on urinary tract and bowel dysfunction in preclinical research.Materials and MethodsThe literature search was conducted using three databases: Ovid (Medline, Embase) and PubMed. Articles were included if they reported on stimulation parameters in animal studies for lower urinary tract or bowel dysfunction as a primary outcome. Methodological quality assessment was performed using the SYRCLE Risk of Bias (RoB) tool for animal studies.ResultsTwenty-two articles were eligible for this systematic review and various aspects of stimulation parameters were included: frequency, intensity, pulse width, stimulation signal, timing of stimulation, and unilateral vs. bilateral stimulation. In general, all experimental studies reported an acute effect of SNM on urinary tract or bowel dysfunction, whereas at the same time, various stimulation settings were used.ConclusionsThe results of this systematic review indicate that SNM has a positive therapeutic effect on lower urinary tract and bowel dysfunction. Using low-frequency-SNM, high-frequency-SNM, bilateral SNM, and higher pulse widths showed beneficial effects on storage and evacuation dysfunction in animal studies. An increased variability of stimulation parameters may serve as a basis for future improvement of the effect of SNM in patients suffering from urinary tract or bowel dysfunction.     

Subcutaneous Peripheral Nerve Stimulation Treatment for Chronic Pelvic Pain

Two cases of chronic pelvic pain of unknown etiology with symptoms referable to the low abdominal wall are presented. These patients are often difficult to manage because of multiple causes and multiple pathways for pain transmission from the pelvis. In these cases, the patients’ complaints were refractory to medication management, as well as diagnostic and therapeutic nerve blockade. After careful evaluation, a successful trial of peripheral nerve stimulation was followed by permanent implantation of low abdominal subcutaneous leads and a pulse generator device. The patients reported excellent relief of their chronic pelvic pain. The use of neuromodulation via peripheral stimulation deserves further investigation as an alternative to spinal cord stimulation for chronic pelvic pain.     

Latency of compound muscle action potentials of the anal sphincter after magnetic sacral stimulation

The aim of this study was to present the failure rate and normal values for motor latency of the anal sphincter after magnetic sacral stimulation (LMSS) using a modified recording technique. A bipolar sponge electrode was placed in the anal canal for recording. A ground electrode was placed in the rectum to reduce stimulus artifact. Magnetic stimulation was induced through a twin coil energized by a Maglite-r25 generator. Two groups were examined: 14 healthy volunteers and 14 patients with a spinal cord injury (SCI) above the conus. Nine of 56 studies (16%) failed. There were no significant differences in latency between right- and left-sided stimulation or between the healthy group and the SCI patients. As described, LMSS measurements are minimally invasive and have a low failure rate. They may be used to test the integrity of the distal motor pathway in patients with bladder or bowel dysfunction who may benefit from continuous electrical sacral root stimulation.     

Sacral nerve stimulation in fecal incontinence; efficacy and safety

Fecal incontinence is common due to various reasons. Conservative therapy of fecal incontinence may sometimes be effective in improving function, but usually many patients require surgery. Sacral nerve stimulation is another treatment modality which gained interest, and appears to be an alternative method that is successful with low morbidity. With the approval of the local ethical committee a total of 14 patients with rectal incontinence had undergone trial stimulation of sacral neuromodulation after failure of conservative treatment modalities. The implantations were performed under surgical sterile conditions with fluoroscopic guidance through the S3 foramen. After correct placement 0.5-2 V, 15 /min, pulse width 210 micro s stimulus was given. The patients had trial period longer than 6 weeks; 9 of 14 patients responded positively to the trial period. Of these 1 had permanent implantation, 3 were booked for permanent implantation, and 2 of the patients had complete incontinence relief from the trial period. Evaluating the data and the results of our study we may conclude that sacral nerve stimulation is an emerging surgical technique to produce a clinically beneficial physiological effect on the lower bowel, pelvic floor and anal canal.     

Sacral Neuromodulation in Patients With Neurogenic Lower Urinary Tract Dysfunction: A Multicenter Retrospective Study From China

ObjectivesThis retrospective study aimed to determine the effectiveness of sacral neuromodulation (SNM) on neurogenic lower urinary tract dysfunction (NLUTD) and analyze the predictive factors.Materials and MethodsFrom January 2012 to January 2020, 152 subjects with NLUTD from four medical centers in China received SNM test stimulation. Subjects were assessed via bladder diaries, postvoid residual volumes (PRVs) and neurogenic bowel dysfunction (NBD) scores before and during the testing period. Patients who showed a minimum 50% improvement in symptoms through the SNM test phase were eligible for permanent SNM implantation.ResultsThe pooled success rate for chronic urinary retention was 31.0% (40/129), which was significantly lower (p < 0.05) than the rates for frequency-urgency (64.8%, 59/91), urinary incontinence (65.2%, 30/46), and NBD score (61.7%, 82/133). The results of the risk factor analysis showed that the urinary storage symptom was a statistically significant positive predictor (p = 0.001).ConclusionsIn conclusion, SNM is an effective and reliable method for treating NLUTD, especially in patients with urinary storage symptoms. Although not all of the symptoms in every patient can be resolve, SNM still might be a superior choice together with other treatment procedures.     

Evoked magnetic fields as a tool to optimize therapeutic electrical stimulation of the sacral surface

Magnetoencephalography (MEG) was used to measure the somatosensory evoked fields in six healthy males undergoing sacral surface therapeutic electrical stimulation, a recently introduced treatment for chronic urinary dysfunction. This study was performed to investigate the utility of MEG to optimize the stimulation parameters. Strong or weak electrical stimuli were applied to small or large surface electrodes placed over the bilateral sacral surfaces. The peak latency and strength of the equivalent current dipole were evaluated at the first peak originating from the primary somatosensory cortex (M30). There was no difference in M30 latency in response to stimulation intensity or electrode size. However, a larger equivalent current dipole strength was obtained in response to higher stimulus intensities, which indicated a more effective stimulus on the sacral surface. The present MEG study shows that stronger stimuli given through large electrodes evoke larger responses than small stimuli through small electrodes. The study also suggests that MEG can be used as an objective tool to monitor whether therapeutic stimulation parameters are appropriate.     

Epidural electrical stimulation for spinal cord injury

A long-standing goal of spinal cord injury research is to develop effective repair strategies, which can restore motor and sensory functions to near-normal levels. Recent advances in clinical management of spinal cord injury have significantly improved the prognosis, survival rate and quality of life in patients with spinal cord injury. In addition, a significant progress in basic science research has unraveled the underlying cellular and molecular events of spinal cord injury. Such efforts enabled the development of pharmacologic agents, biomaterials and stem-cell based therapy. Despite these efforts, there is still no standard care to regenerate axons or restore function of silent axons in the injured spinal cord. These challenges led to an increased focus on another therapeutic approach, namely neuromodulation. In multiple animal models of spinal cord injury, epidural electrical stimulation of the spinal cord has demonstrated a recovery of motor function. Emerging evidence regarding the efficacy of epidural electrical stimulation has further expanded the potential of epidural electrical stimulation for treating patients with spinal cord injury. However, most clinical studies were conducted on a very small number of patients with a wide range of spinal cord injury. Thus, subsequent studies are essential to evaluate the therapeutic potential of epidural electrical stimulation for spinal cord injury and to optimize stimulation parameters. Here, we discuss cellular and molecular events that continue to damage the injured spinal cord and impede neurological recovery following spinal cord injury. We also discuss and summarize the animal and human studies that evaluated epidural electrical stimulation in spinal cord injury.     

Findings with Bilateral Sacral Neurostimulation: Sixty‐two PNE‐Tests in Patients with Neurogenic and Idiopathic Bladder Dysfunctions

We performed bilateral PNE (peripheral nerve evaluation) tests to identify which diagnostic groups are the most likely to profit from bilateral sacral neuromodulation since the results published so far have been obtained exclusively on the basis of unilateral sacral root stimulation. In contrast to the original unilateral technique, we performed bilateral PNE test stimulation in 62 patients (36 with urinary retention symptoms and 26 with overactive detrusor; 21 with idiopathic and 41 with neurogenic bladder dysfunction) over 3–4 days. We used an advanced electrode, model #3057 (Medtronic, Inc. Minneapolis, MN). The stimulation amplitudes were adjusted individually for each side. Retrospectively, we analyzed our data according to diagnostic characteristics (retention vs. overactive bladder and neurogenic vs. idiopathic) of those patients who had positive PNE test results. The PNE test was successful in 32 patients (51.6%). Of these, 27 suffered from neurogenic bladder dysfunction; in five cases the cause was idiopathic. We conclude that bilateral PNE test stimulation with side‐specific amplitude adjustment and the use of advanced PNE electrodes led to a positive PNE result in 51.6% of the patients, which is a substantially increased response rate compared to previous studies. Of the diagnostics groups, the group with neurogenic bladder dysfunctions showed the highest response rate.     

Results of neuromodulation for the management of chronic pain

Background and purpose : Neuromodulative treatment of chronic pain syndromes is a modern mode of treatment of neuropathic and ischaemic pain. Its effectiveness is well documented in the literature. The objective of this work is to present the results of treatment of chronic pain syndromes on the basis of eight-year experience in our department. Material and methods : Since 2002, we have conducted 9 operations of motor cortex stimulation (MCS), 2 of deep brain stimulation (DBS), 45 of spinal cord stimulation (SCS) and 5 of sacral root stimulation (SRS) in the treatment of chronic pain. Results : We obtained good long-term results of neuromodulation in the form of clinical improvement (> 50%) in 4 of 9 patients with MCS (44%), in 13 diagnosed with failed back surgery syndrome (FBSS), 8 with other neuropathic pain, and 11 with angina pectoris from a group of 45 treated with SCS. Sacral root stimulation has been successful in 3 of 5 patients with perianal pain. The best treatment results in SCS, although not statistically significant, were observed in patients treated due to FBSS (13 out of 15) and angina pectoris (11 out of 15) (p = 0.12). In patients with neuropathic pain, peripheral and central, improvement was obtained in 8 out of 15 patients. Conclusions : A good indication for spinal cord stimulation is FBSS and angina pectoris. Motor cortex stimulation is helpful in the treatment of chronic central neuropathic pain. Further observations and a larger group of patients are necessary for a reliable assessment of the effectiveness of neuromodulative treatment of chronic pain in our clinic.     

Multimodal treatment for spinal cord injury: a sword of neuroregeneration upon neuromodulation

Spinal cord injury is linked to the interruption of neural pathways,which results in irreversible neural dysfunction.Neural repair and neuroregeneration are critical goals and issues for rehabilitation in spinal cord injury,which require neural stem cell repair and multimodal neuromodulation techniques involving personalized rehabilitation strategies.Besides the involvement of endogenous stem cells in neurogenesis and neural repair,exogenous neural stem cell transplantation is an emerging effective method for repairing and replacing damaged tissues in central nervous system diseases.However,to ensure that endogenous or exogenous neural stem cells truly participate in neural repair following spinal cord injury,appropriate interventional measures(e.g.,neuromodulation)should be adopted.Neuromodulation techniques,such as noninvasive magnetic stimulation and electrical stimulation,have been safely applied in many neuropsychiatric diseases.There is increasing evidence to suggest that neuromagnetic/electrical modulation promotes neuroregeneration and neural repair by affecting signaling in the nervous system;namely,by exciting,inhibiting,or regulating neuronal and neural network activities to improve motor function and motor learning following spinal cord injury.Several studies have indicated that fine motor skill rehabilitation training makes use of residual nerve fibers for collateral growth,encourages the formation of new synaptic connections to promote neural plasticity,and improves motor function recovery in patients with spinal cord injury.With the development of biomaterial technology and biomechanical engineering,several emerging treatments have been developed,such as robots,brain-computer interfaces,and nanomaterials.These treatments have the potential to help millions of patients suffering from motor dysfunction caused by spinal cord injury.However,large-scale clinical trials need to be conducted to validate their efficacy.This review evaluated the efficacy of neural stem cells and magnetic or electrical stimulation combined with rehabilitation training and intelligent therapies for spinal cord injury according to existing evidence,to build up a multimodal treatment strategy of spinal cord injury to enhance nerve repair and regeneration.