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.     

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.     

Prolonged electrical stimulation causes no damage to sacral nerve roots in rabbits

Previous studies have shown that, anode block electrical stimulation of the sacral nerve root can produce physiological urination and reconstruct urinary bladder function in rabbits. However, whether long-term anode block electrical stimulation causes damage to the sacral nerve root remains unclear, and needs further investigation. In this study, a complete spinal cord injury model was established in New Zealand white rabbits through T9–10 segment transection. Rabbits were given continuous electrical stimulation for a short period and then chronic stimulation for a longer period. Results showed that compared with normal rabbits, the structure of nerve cells in the anterior sacral nerve roots was unchanged in spinal cord injury rabbits after electrical stimulation. There was no significant difference in the expression of apoptosis-related proteins such as Bax, Caspase-3, and Bcl-2. Experimental findings indicate that neurons in the rabbit sacral nerve roots tolerate electrical stimulation, even after long-term anode block electrical stimulation.     

Bladder emptying by intermittent electrical stimulation of the pudendal nerve

Persons with a suprasacral spinal cord injury cannot empty their bladder voluntarily. Bladder emptying can be restored by intermittent electrical stimulation of the sacral nerve roots (SR) to cause bladder contraction. However, this therapy requires sensory nerve transection to prevent dyssynergic contraction of the external urethral sphincter (EUS). Stimulation of the compound pudendal nerve trunk (PN) activates spinal micturition circuitry, leading to a reflex bladder contraction without a reflex EUS contraction. The present study determined if PN stimulation could produce bladder emptying without nerve transection in cats anesthetized with alpha-chloralose. With all nerves intact, intermittent PN stimulation emptied the bladder (64 +/- 14% of initial volume, n = 37 across six cats) more effectively than either distention-evoked micturition (40 +/- 19%, p < 0.001, n = 27 across six cats) or bilateral intermittent SR stimulation (25 +/- 23%, p < 0.005, n = 4 across two cats). After bilateral transection of the nerves innervating the urethral sphincter, intermittent SR stimulation voided 79 +/- 17% (n = 12 across three cats), comparable to clinical results obtained with SR stimulation. Voiding via intermittent PN stimulation did not increase after neurotomy (p > 0.10), indicating that PN stimulation was not limited by bladder-sphincter dyssynergia. Intermittent PN stimulation holds promise for restoring bladder emptying following spinal injury without requiring nerve transection.     

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.     

Long-term anodal block stimulation at sacral anterior roots promoted recovery of neurogenic bladder function in a rabbit model of complete spinal cord injury

A complete spinal cord injury model was established in experimental rabbits using the spinal cord clip compression method.Urodynamic examination was performed 2 weeks later to determine neurogenic bladder status.The rabbits were treated with anodal block stimulation at sacral anterior roots for 4 weeks.Electrical stimulation of sacral anterior roots improved urodynamic parameters of neurogenic bladder in rabbit models of complete spinal cord injury,effectively promoted urinary function,and relieved urinary retention.Immunohistochemistry results showed that a balance was achieved among expression of muscarinic receptor subunits M2,M3,ATP-gated ion channel P2X3 receptors,and β2-adrenergic receptor,and nerve growth factor expression decreased.These results suggested that long-term sacral anterior root stimulation of anodal block could be used to treat neurogenic bladder in a rabbit model of complete spinal cord injury.     

The role of neuropeptides in the sacral autonomic reflex pathways of the cat

Immunohistochemical and pharmacological studies were conducted to examine the origin and function of peptidergic nerves in the sacral autonomic system of the cat. Leucine-enkephalin (L-Enk) immunoreactivity was identified in nerve terminals in peripheral ganglia on the surface of the urinary bladder and in the parasympathetic nucleus in the sacral spinal cord. In colchicine-treated animals L-Enk was also detected in sacral preganglionic neurons (sPGN) identified by retrograde transport of a fluorescent dye. L-Enk terminals in bladder ganglia are believed to arise from sPGN since the terminals were eliminated by transection of the sacral ventral roots. Pharmacological studies indicated that exogenous as well as endogenously released enkephalins have an inhibitory action at both ganglionic and spinal sites in the sacral outflow to the urinary bladder. Peptides were also associated with afferents nerves in the sacral autonomic system. The distribution of substance P, VIP and cholecystokinin in the sacral dorsal horn paralleled the distribution of visceral afferent projections as demonstrated with HRP techniques. Dye labeling combined with immunohistochemistry revealed that some dorsal root ganglion cells projecting to the pelvic viscera contain substance P or VIP.     

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.     

A Portable Device for Experimental Treatment of Neurogenic Detrusor Overactivity

The objective of this study was to evaluate the effect of automatic event‐driven electrical stimulation on the dorsal penile/clitoral nerve for management of neurogenic detrusor overactivity in spinal cord injured subjects. In order to reach the objectives it was necessary to design and realize a portable device for ambulatory urodynamic studies which was able to activate an electrical stimulator when the detrusor pressure exceeded a certain threshold. The developed device was repeatedly tested in a healthy subject and subsequently tested in a spinal cord injured subject. In testing the automatic event‐driven system in the spinal cord injured subject, detrusor contractions were successfully inhibited until a certain bladder volume was reached and no incontinence episodes were observed prior to disabling the system. The preliminary results indicate that automatic event‐driven electrical stimulation on the dorsal penile/clitoral nerve can inhibit involuntary detrusor contractions in spinal cord injured subjects and hereby restore continence and increase bladder capacity.     

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.     

Discharge patterns of motility-regulating neurons projecting in the lumbar splanchnic nerves to visceral stimuli in spinal cats

Reflexes in visceral preganglionic motility-regulating (MR) neurons which project in the lumbar splanchnic nerves were investigated in acutely spinalized cats. Some neurons were analyzed before and after spinalization. The stimuli used were mechanical stimulation of mucosal skin of the anus and of perianal (perigenital) hairy skin, and distension and contraction of urinary bladder and colon. Most MR neurons exhibited a reflex pattern which consists of the following components: excitation upon bladder distension, inhibition or no effect upon colon distension and excitation (or, rarely, no effect) upon anal stimulation. This is the reflex pattern of MR1 neurons. Some neurons were excited by anal stimulation but not affected from the colon and urinary bladder. Some were inhibited by anal and perianal stimulation but otherwise exhibited the reflex patterns of the MR1 neurons. Analysis of the reflexes before and after spinalization showed that, in particular, inhibition elicited by anal, perianal and bladder stimulation was abolished; inhibition elicited from the colon was enhanced after spinalization. It is concluded that the reflexes elicited in preganglionic lumbar visceral neurons by the natural stimuli probably use spinal pathways, with the afferent input occurring at the sacral spinal cord. These spinal reflex pathways are probably controlled by descending inhibitory and excitatory spinal systems from the supraspinal neuraxis.     

The laparoscopic implantation of neuroprothesis to the sacral plexus for therapy of neurogenic bladder dysfunctions after failure of percutaneous sacral nerve stimulation

Objectives: To report about our first short series of laparoscopic implantation of neuroprothesis—LION procedure—to the sacral plexus for treatment of different neurogenic bladder dysfunctions in patients in whom percutaneous sacral nerve stimulation (SNS) failed. Material and Methods: A unilateral sacral LION procedure was performed in four patients with a refractary interstitial cystitis, in 13 patients with refractory bladder overactivity (multiple sclerosis N= 8, spina bifida N= 1, incomplete paraplegia N= 2, diabetic cystopathy N= 1), one patient with a neurogenic bladder incontinence by Parkinson syndrome, and in four patients for treatment for bladder atonia (Fowler's syndrome). In all patients, not only previous medical treatments but also SNS by transforaminal implantation had failed. Laparoscopic exposure of the sacral nerves roots S2 to S4/5 is performed by a transperitoneal approach and a quad electrode is placed perpendicular to the sacral nerve roots for postoperative global stimulation of these sacral nerve roots. Results: All procedures were performed successfully by laparoscopy without any complications. The mean operative time for such a procedure was 34 min. In two patients of the series postoperative neuromodulation failed. In all further 19 patients with an actual follow‐up varying between three months and three years, neuromodulation is still working successfully. Conclusions: Our results underscore that the sacral LION procedure to the sacral plexus is effective and safe for treatment divers neurogenic bladder dysfunctions even after failure of the classical percutaneous technique of implantation.     

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.     

The Laparoscopic Implantation of Neuroprothesis (LION) Procedure to Control Intractable Abdomino‐Pelvic Neuralgia

Objective. To present different aspects and advantages of the laparoscopic implantation of a peripheral nerve stimulator adjacent to the pelvic nerves, aimed at treating intractable pelvic neuralgia by means of neuromodulation—the laparoscopic implantation of neuroprothesis (LION) procedure. Materials and Methods. We report here a series of three patients with different types and etiologies of chronic pelvic neuralgia who underwent laparoscopy for implantation of a peripheral nerve stimulator for neuromodulation, the first for neuromodulation of the ilioinguinal and pudendal nerves, the second for neuromodulation of the sciatic nerve, and the third for neuromodulation of the sacral nerve roots. In all three patients, the neuralgia was refractory to medical management and had profound socioeconomic consequences for the patients. Results. Laparoscopic implantation of neuroelectrodes was successfully performed in all three patients and resulted significant diminution of pain without need for further medical treatment. Conclusions. Laparoscopy allows optimal implantation of electrodes on all pelvic nerves through a minimally invasive approach. In addition, it permits new applications of neuromodulation for pelvic polyneuropathies or mononeuropathy, not covered by classical spinal cord or transcutaneous techniques.     

Bladder and urethral sphincter responses evoked by microstimulation of S2 sacral spinal cord in spinal cord intact and chronic spinal cord injured cats

Urinary bladder and urethral sphincter responses evoked by bladder distention, ventral root stimulation, or microstimulation of S2 segment of the sacral spinal cord were investigated under alpha-chloralose anesthesia in cats with an intact spinal cord and in chronic spinal cord injured (SCI) cats 6-8 weeks after spinal cord transection at T9-T10 spinal segment. Both SCI and normal cats exhibited large amplitude reflex bladder contractions when the bladder was fully distended. SCI cats also exhibited hyperreflexic bladder contractions during filling and detrusor-sphincter dyssynergia during voiding, neither was observed in normal cats. Electrical stimulation of the ventral roots revealed that the S2 sacral spinal cord was the most effective segment for evoking large amplitude bladder contractions or voiding in both types of cats. Microstimulation with a stimulus intensity of 100 microA and duration of 30-60 s via a single microelectrode in the S2 lateral ventral horn or ventral funiculus evoked large amplitude bladder contractions with small urethral contractions in both normal and SCI cats. However, this stimulation evoked incomplete voiding due to either co-activation of the urethral sphincter or detrusor-sphincter dyssynergia. Stimulation in the S2 dorsal horn evoked large amplitude sphincter responses. The effectiveness of spinal cord microstimulation with a single electrode to induce prominent bladder and urethral sphincter responses in SCI animals demonstrates the potential for using microstimulation techniques to modulate lower urinary tract function in patients with neurogenic voiding dysfunctions.     

Restoration of micturition using microelectric current in experimentally induced spastic urinary bladder in rabbits

The 29 rabbits used in this study were divided into three groups, A (A1 and A2), B, and C. In subgroup A1, 4 animals were used in order to verify whether the contact of an electrode to the sacral nerves results in some abnormality of voiding reflex. In subgroups A1 and A2 (4 animals each) we further studied the micturition function using three parameters: (i) urinary bladder fluoroscopy and radiography, (ii) cystomanometry, and (iii) electromyography of the pelvic floor muscles (external sphinter). In group B (9 rabbits) spastic paraplegia and micturition disturbances resulted from spinal cord compression that was induced by inserting a balloon catheter into the T11-T12 intervertebral foramen. In this group the parameters studied revealed a spastic urinary bladder in all animals. Finally, the 12 animals of group C were rendered paraplegic as described in group B, and microelectrodes were placed over the sacral nerves as in subgroup A1. By applying a specific sequence of sacral nerve stimulation we succeeded in satisfactory urinary bladder emptying as confirmed by the micturition parameters studied: The urinary bladder pressure decreased from 65 +/- 3 to 28 +/- 3 mm Hg. The pelvic floor muscle amplitude was lowered from 130 +/- 7 to 20 +/- 3 microV, and finally the radiological bladder size also decreased from 38 cm2 before voiding to 18 +/- 3 cm2 after voiding. These results indicate that microelectric current stimulation of the sacral nerves, when applied under a specific sequence, could rather satisfactorily restore micturition disturbances, at least in this experimental animal.     

The various types of neurogenic bladder dysfunction: an update of current therapeutic concepts

Increased experience with treatment strategies developed during the last 10 years in the field of neurourology justifies an update of current therapeutic concepts. Based on a rather simple, but clinically useful, classification of detrusor-sphincter dysfunction the therapeutic concepts now available for four prototypes of detrusor-sphincter dysfunction are discussed. (1) For the combination of a hyperreflexive detrusor with a hyperreflexive (spastic) sphincter, characteristic for the reflex- and the uninhibited neuropathic bladder, detrusor-sphincter dyssynergia (DSD) is still the greatest problem, and transurethral sphincterotomy is the method of choice if this situation cannot otherwise be managed. One concept is to convert detrusor hyperreflexia into hyporeflexia by adequate pharmacotherapy, which is nowadays available, and to assist or to accomplish bladder emptying by clean intermittent (self-) catheterisation (CIC) with the advantage of dry intervals in between. Japanese colleagues recommend bladder overdistension during the spinal shock phase to achieve detrusor hyporeflexia, but this procedure is rather decisive at an early stage of the disability, leaving the detrusor no chance for further rehabilitation. Another possibility is rhizotomy of the sacral posterior roots to eliminate detrusor hyperreflexia, and the simultaneous implantation of a sacral anterior root stimulator (Brindley) to achieve electrically induced micturition. From our personal experience with 12 patients this concept is ideal for female patients with unbalanced reflex bladder and otherwise uncontrollable reflex incontinence. (2) The combination of a weak detrusor with a spastic sphincter is a clear indication for CIC, as the bladder is emptied regularly, and due to the spastic sphincter, the patient stays continent as long as controlled fluid intake prohibits overflow incontinence. The implantation of an anterior sacral root stimulator is an alternative approach provided that at least weak reflex detrusor contractions are present. (3) With the combination of an areflexive or hyporeflexive detrusor and a flaccid pelvic floor, passive voiding by abdominal straining or by the Credé manoeuvre is usually recommended, but should be replaced by CIC if this mechanism of bladder emptying creates unphysiological high and dangerous intravesical pressures, or if vesico-uretero-renal reflux is present. Neurogenic urinary stress incontinence is usually associated with this type of lesion and can be successfully treated by the implantation of an artificial urinary sphincter (Scott). However in two thirds of the patients with neurogenic bladder dysfunction, additional, usually operative treatment is necessary to meet the criteria for implantation. Moreover, a 30% rate of repair operations must be accepted by patients, but is becoming less frequently required with an improved design of the device.(ABSTRACT TRUNCATED AT 400 WORDS)     

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 ).     

Urological outcome in female patients with spinal cord injury: the effectiveness of intermittent catheterisation

A review of 52 female patients with spinal cord injury is presented. Twenty five of 38 patients seen within 3 months of their injury were discharged on a clean intermittent catheterisation regime. Of the 14 patients seen at an interval of 3 months or greater after the injury, only 3 practised clean intermittent catheterisation but 8 had a long-term indwelling urethral catheter as the method of management. At 49 months median follow-up, only 14 (50%) continue on the programme of intermittent catheterisation and 9 (32%) are dry. This lack of success was due to incontinence, despite drug therapy in 17 patients. Recurrent symptomatic urinary tract infection occurred in 10 (36%). Thirteen of the 14 patients (92%) on long-term indwelling urethral catheter developed complications. Five patients voided normally. Automatic bladder emptying was employed in only 2 patients but was associated with the development of a non-functioning kidney in 1 and severe incontinence in another. Upper tract changes occurred in 7 patients (13%) including 3 on indwelling catheter drainage and 2 on intermittent catheterisation. Four patients have had implantation of the Brindley intradural sacral anterior root stimulator because of recurrent symptomatic urinary tract infections and incontinence in all 4. Post-operatively the incidence of infection has been reduced. Improvement in the degree of incontinence is related to the completion of posterior root section. Those patients who have no alternative to long-term catheter drainage are managed by the suprapubic route to avoid urethral incompetence. This is combined with catheter clamping for 2 hours daily to maintain bladder capacity and anti-cholinergic therapy to reduce detrusor contractility.(ABSTRACT TRUNCATED AT 250 WORDS)