Research priorities for urological care following spinal cord injury: recommendations of an expert panel.

OBJECTIVE: A multidisciplinary panel of experts from Canada and the United States was convened by the Ontario Neurotrauma Foundation (ONF) to establish research priorities in the area of urological care following spinal cord injury (SCI). DESIGN: The panel reviewed a synthesis of published literature in five areas of urology, identified emerging opportunities in the private and public sector, and used a modified Delphi approach to reach consensus on priorities for funding. RESULTS: The panel recommendations included: clinical trials of the safety and efficacy of M3 receptor specific anti-muscarinic agents for bladder hyperactivity in SCI patients; development and testing of protocols for sacral nerve electrostimulation without sacral afferent neurectomy for management of micturition - including selective stimulation of sacral nerve fibers, high frequency blocking of the pudendal nerve to minimize the risk of urethral sphincter co-contraction and genital nerve stimulation for bladder inhibition and incontinence management; clinical trials of the efficacy and safety of intra-urethral valve catheters; trials of the efficacy of probiotics for bacterial interference i.e. to reduce colonization by uropathogens and manage the dual problems of infection and pathogen resistance to anti-microbials: innovations in the prevention or treatment of stone disease (ureteral, bladder and kidney). CONCLUSIONS: The recommendations form the strategic priorities of the ONF SCI grants program for Ontario-based investigators and their partnerships with out-of-province collaborators and organizations.

Use of a neuromuscular stimulator to increase anal sphincter pressure.

OBJECTIVES: The objective of this study was to determine if short periods of electrical stimulation with perianal electrodes could increase anal pressures. MATERIAL AND METHODS: Anorectal responses to electrical stimulation were evaluated in five healthy SCI patients. Anorectal pressures were recorded with a small pressure-recording balloon before, during, and immediately following stimulation. A battery-powered stimulator with self-adhering surface electrodes, two inches in diameter was used. Stimulating parameters consisted of 300 micros pulse duration, 35 Hz stimulating frequency. A current response study was conducted by using short periods of electrical stimulating with currents from 0-100 mA until a maximal pressure was recorded. Each current setting was conducted for 13.2+/-9.7 s before increasing to the next higher current, and fatigue was reduced by including a 5-minute rest between stimulations. RESULTS: Four of the five subjects had strong anal contractions with perianal stimulation. Increases in pressure ranged from 38 to 125 cm H2O based on maximal responses at currents ranges of 60 to 100 ma. Even during the short periods of stimulation used here, fatigue was apparent. There was an average drop of 11% in anal pressure over the 13 s of stimulation. Rectal pressures were unchanged with perianal stimulation. CONCLUSIONS: Perianal stimulation with surface electrodes is an approach that might be considered in the future for management of fecal incontinence in individuals with spinal cord injury. Further studies are needed to assess the feasibility of using chronic perianal surface electrical stimulation to sustain anal sphincter contractions.

Evaluation of a suture electrode for direct bladder stimulation in a lower motor neuron lesioned animal model.

The purpose of this study was to evaluate a "suture" type electrode for direct bladder stimulation in an animal model of a lower motor neuron lesion. During an initial surgery, five male cats were instrumented under anesthesia using multistranded, 316 LVM, stainless-steel, wire electrodes implanted on the bladder wall serosa above the trigone area. Electrodes were constructed with a needle attached to the end that was removed after suturing the electrode in place. Additional instrumentation included urinary bladder catheters (tubes) for pressure recording and filling, and hook type electrodes for leg and pelvic floor electromyography recording. Chronic bladder filling and stimulation studies were conducted in tethered animals three to four weeks following surgery. To test these electrodes in a spinal cord injury model, a lower motor neuron lesion was performed including the sacral cord and complete nerve roots at L6 and below. These animals were evaluated during weeks 3 and 10 after injury. Direct bladder stimulation induced active contractions and voiding both before and after spinal cord injury. Effective stimulation parameters consisted of 40 pulses per s, 300 micros to 1 ms pulse duration, a stimulation period from 3 to 4 s, and a stimulation current from 10 to 40 mA. Fluoroscopy revealed an open membranous urethra during stimulation and following stimulation. A small diameter penile urethra was observed to limit flow. Postmortem evaluation of the suture electrode revealed no abnormalities such as corrosion, migration into the bladder lumen or displacement. These findings indicate that suture electrodes are suitable and effective for short-term implantation in the lower motor neuron animal model.

Optimization of sacral ventral root stimulation following SCI: two case reports with six-month follow-up.

Sacral ventral root stimulation in conjunction with sacral dorsal rhizotomy has been effective in promoting voiding in individuals with upper-motor-neuron spinal cord injury. We report on two patients who had variable voiding responses to stimulation during the first six months after electrode implantation. We used videourodynamic records and daily voiding records to characterize their voiding difficulties. Different methods were used to improve voiding, including seating adjustments and changes in stimulation parameters. The first patient was unable to empty his bladder on a regular basis with stimulation using 24 pulses per sec stimulating frequency for the first two months after implantation. Voiding was substantially improved by using 35 pulses per sec. At the end of six months, he is regularly emptying his bladder with stimulation and is on an every-second-day bowel program. However, his bowel program has been irregular. The second patient had very good voiding when stimulation was applied in bed, but he had poor voiding with high residual volumes when sitting in his wheelchair. Voiding was improved when he used a wheelchair cushion that was cut out in the back or lifted his buttocks off the chair. These procedures appeared to reduce perineal pressures. This patient has bowel care on alternate days and his bowel care time has been reduced following implantation of the device. Neither of the patients experienced an erection with the device. Both patients feel positive about their implant experience.

Multielectrode nerve cuff stimulation of the median nerve produces selective movements in a raccoon animal model.

In this study, an electrode system consisting of twelve small platinum dot electrodes imbedded in a spiral silicone rubber insulating cuff was used to investigate the feasibility of selective (regional) stimulation of the median nerves of the raccoon. Acute experiments in four raccoons consisted of functional responses observations, isometric force recordings from tendon attachments and postmortem fascicular mapping. Functional responses (elbow, wrist and/or digit flexion, pronation and/or thumb abduction) to selective stimulation were noted as dependent upon cuff electrode configuration (longitudinal tripole with and without field steering, as well as a transverse bipolar arrangement) and current level (threshold, 1/2 maximal, maximal). Muscle force recruitment curves (force as a function of stimulus amplitude) were plotted for flexor digitorum superficialis, flexor digitorum profundus, flexor carpi radialis, palmaris longus and pronator teres of three raccoons. Fascicular maps at the level of the nerve cuff were created indicating the approximate position of innervation to each of the aforementioned muscles, as well as other innervation such as paw fascicles, sensory fascicles, and elbow innervation (such as coracobrachialis). The greatest selectivity was observed at or near threshold current levels. In all four raccoons studied, a threshold electrode choice and stimulation strategy could be identified enabling selective production of either digit flexion, wrist flexion and/or digit and wrist flexion. It was possible to elicit a selective pronation response at threshold in three of the four animals. Selective elbow flexion at threshold could be produced in all four experiments. With stronger currents, additional movements were usually induced. The raccoon therefore appears to be a suitable, if challenging, animal model for further development of not only nerve cuff electrode approaches but perhaps other stimulation electrode technologies prior to human neuroprosthetic studies.

Testing peripheral somatosensory neuroprostheses by recording from raccoon cortex.

A topologically organized representation of the body surface exists within the mammalian somatosensory cortical areas such that stimulation of a part of the body surface will produce a response in a localized region of the contralateral somatosensory cortex. Because of this topography, we propose that the selectivity of a peripheral somatosensory neuroprosthetic electrode array can be tested by noting whether the locus of maximum activation in the cortex moves in a consistent manner when differing portions of the array are stimulated. We further propose that the raccoon might well be the ideal animal in which to test this hypothesis, since the raccoon has a rather unique cortical somatosensory area where each digit is represented in individual subgyri around the tri-radiate sulcus. To demonstrate the feasibility of this concept, a pilot study was carried out in one raccoon under barbiturate anesthesia. The median nerve was stimulated via selective quadrants of a nerve cuff array of four tripolar electrodes implanted around the nerve. Cuff stimulation produced short-latency evoked surface potentials in the digit areas of the raccoon first somatosensory cortex. Response selectivity could be demonstrated, as could a separation between thresholds for producing movement or producing cortical evoked potentials. The sensory and motor responses elicited were consistent with the orientation of the median nerve within the cuff as determined by a postmortem identification of the muscle innervation pattern of the nerve.

Do direct current electric fields enhance micturition in the spinal cat?

Changes in micturition behavior and motoneuron ultrastructure were studied in spinal cats to determine the effects of direct current (DC) electric field treatment. Adult cats received a complete injury at T8. A treatment group with an implanted 15 microA DC source and electrodes positioned near the lesion site was compared with non-treatment groups that were either operated or unoperated. Both bladder emptying with Crede and the withdrawal reflex were improved in the treatment group compared with the non-treatment group. Urodynamic procedures showed that high urethral resistance and pelvic floor activity following spinal injury was partially reduced in the stimulated cat, indicating inhibition of the urethral sphincter. The ultrastructural analysis of Onuf's nucleus suggested a similar synaptic input in all three groups. In conclusion, possible activation of inhibitory processes and/or neural plasticity best explain the early improvement of bladder function seen following electrical stimulation.

Effects of low charge injection densities on corrosion responses of pulsed 316LVM stainless steel electrodes.

The safe charge injection density for pulsing of 316LVM electrodes has been reported to be 40 microC/cm2. However, only 20 microC/cm2 is available for nonfaradic charge transfer and double layer charge injection. Therefore, we evaluated long term pulsing at 20 microC/cm2 with capacitor coupling.

Direct bladder stimulation with percutaneous electrodes and impedance monitoring of volume in an SCI animal model.

Bladder responses to percutaneous electrodes were investigated with stimulation in three male spinal cats. The animals had been spinalized (T1 level lesion) 10 weeks prior to these studies and had been instrumented with chronic bladder had been spinalized (T1 level lesion) 10 weeks prior to these studies and had been instrumented with chronic bladder wall electrodes and suprapubic bladder catheters for filling and pressure recording. percutaneous stimulation in tethered animals was conducted wit hook electrodes inserted with a needle in the abdomen bilaterally adjacent to the bladder trigone. Stimulation was conducted with 40 Hz pulse trains of 10 to 30 mA for three seconds. Stimulation with both percutaneous and chronic electrodes induced high bladder pressures and voiding. In addition, with chronically implanted electrodes, impedance monitoring of bladder volume was found to be an effective recording technique.

Evaluation of a thin-film peripheral nerve cuff electrode.

This is a study of the reaction of large nerves to implantation using a flexible, thin-film cuff electrode. Cuff electrodes were implanted on the sciatic nerve of three cats. An implantation period of six weeks allowed sufficient time for any injury responses in the nerve and connective tissue sheath around the cuff to develop. The electrode came off the nerve in one of the cats. In the remaining two cats, gross observation following explantation of the electrodes revealed encapsulation of the cuffs without swelling of nerve tissue. Histological evaluation did not demonstrate nerve injury. The nerve cuff electrodes, which are comprised of titanium and iridium coatings on a fluorocarbon polymer substrate, appeared unaffected by the implantation, and connective tissue encapsulation did not adhere to either the polymer substrate or metallization. Evaluation of the electrodes using activated iridium oxide charge injection sites in more extended studies is now being undertaken.

Management of incontinent SCI patients with penile stimulation: preliminary results.

We investigated dorsal penile stimulation for control of incontinence in nine spinal cord impaired (SCI) patients, using a battery-powered home-use stimulator connected to surface electrodes (Unipatch). The efficacy of the penile stimulation was assessed by urodynamic evaluation (NL-2, LifeTech) and surface electrodes (Unipatch); baseline and repeat cystometries (CMG) with and without stimulation were done. Stimulation for home use was begun at threshold parameters for inducing perineal contractions and, after two weeks, was adjusted based upon results. Two subjects successfully completed the study and became continent. One of these patient's CMG demonstrated hyperreflexia and his volume increased from 110 ml to 150 ml after the stimulation protocol. The most effective stimulating parameters were 5 pps, 250 microsec, pulse width and 40 ma current. The other patient also had a hyperreflexic bladder and improved on the protocol. The remaining seven patients did not complete the study for several reasons. Three patients had CMG's that demonstrated areflexia. Stimulation did not alter their bladder function and they dropped out of the program. Three other subjects withdrew because of bothersome sensations even at subthreshold levels and they complained that the technique was cumbersome. Finally, one patient with significant hyperreflexia and incontinence withdrew after trying unsuccessfully and diligently for 10 days. Our encouraging results in two patients with hyperreflexic bladders and decreased sensation suggest that this modality may be effective in this patient group.

Evaluation of direct bladder stimulation with stainless steel woven eye electrodes.

Encouraged by recent clinical reports of micturition induced in patients by direct bladder stimulation, we conducted a study of optimum methods of direct bladder stimulation. During surgery six male cats received eight large surface-area woven eye electrodes sutured to the bladder wall serosa, four on the bladder dome and four adjacent to the trigone area. Two additional small surface-area single knot electrodes were sutured in the trigone area. Suprapubic and intraperitoneal tubes were placed for pressure recording and bladder filling. Leg and pelvic floor EMG electrodes were also used for tethered recordings. One to eight weeks after surgery, optimum stimulation methods were evaluated as the animal freely moved about a urodynamic recording cage. Electrodes in the trigone region were more effective than electrodes on the dome and induced bladder contractions and voiding similar to spontaneously induced voiding with bladder filing. Large surface area, woven eye electrodes, composed of multistranded 316LVM stainless steel wire, were more effective than smaller surface area single knot electrodes. High stimulating frequencies (40 Hz) were better than lower frequencies (10 to 20 Hz), and a 1 millisecond pulse duration was optimal. Pulsing with stimulating currents from 10 to 25 mA induced effective bladder contractions with voiding when applied for 3 seconds. However, lower currents using longer stimulation periods were also effective. Bipolar electrodes with both electrodes on the bladder wall were superior to monopolar arrangements with the positive ground electrode along the animal's back. We concluded that in the able-bodied cat model, bladder contractile activity for micturition can be induced with direct bladder stimulation and with little discomfort. An effective stimulation protocol consists of capacitor-coupled monophasic pulses with large surface area bipolar electrodes in the trigone region. Stimulating parameters of 40 Hz, 1 msec., 10 to 25 mA applied for 3 seconds were optimal. In addition, based on corrosion resistance observations, the electrodes are quite suitable for long-term studies.

Inhibiting the hyperreflexic bladder with electrical stimulation in a spinal animal model.

Uninhibited bladder contractions are a problem in spinal cord injured patients. Accordingly, methods using electrical stimulation to inhibit the bladder were investigated in chronic spinal cord injured (C6-T1) male cats. In unanesthetized, restrained animals, spontaneous bladder contractions were observed after the bladder was filled above the micturition threshold. In 3 of the 5 cats studied, this bladder activity could be inhibited with stimulation of either sacral nerves or pudendal nerves. Pudendal nerve stimulation, however, was more selective than sacral nerve stimulation for inhibition with fewer side effects such as leg spasms. Tibial nerve stimulation was ineffective and caused leg spasms and increased bladder activity. Finally, high-frequency stimulation (1,000 Hz) of the sacral nerves was shown to block bladder contractions in 2 of 3 cats investigated. However, this method had adverse side effects such as leg flexion and secondary bladder contractions. We conclude that pudendal nerve/pelvic floor stimulation at low frequency is a relatively effective method in this model.

Behavioral therapy for urinary incontinence.

Urinary incontinence is a serious and costly problem that affects many patients, especially the elderly. Because this population is growing, many methods of treatment for urinary incontinence have been developed. However, even though the behavioral techniques have been available for years, only recently has the use of formal behavioral methods become more popular as a less invasive alternative for the treatment of incontinence. These methods have proven effective in several series. This article reviews the treatment of types of urinary incontinence with behavioral therapeutic techniques.

Sacral epidural electrodes for voiding in the chronic spinal dog.

Recent reports have shown that electrical stimulation of the bladder wall or sacral nerves is effective for bladder management in the spinal cord injured (SCI) patient. However, less invasive methods are needed for electrode implantation. A modified percutaneous procedure for implanting needle electrodes in the sacral canal was evaluated. Stimulation with these electrodes were effective for inducing voiding with little residual volume after the recovery of bladder reflexes, 3 weeks after experimental spinal cord injury in the dog. An optimum electrode arrangement involved a single midline monopolar electrode located between sacral foramina L7 and S1. However, at low stimulating current, lateral electrodes adjacent to sacral nerves were more effective than midline electrodes for inducing voiding. Stimulation parameters that were effective for daily voiding were 10 pps, 1.5-5 mA, 0.3 ms pulse duration, and 2- to 3-second stimulation periods.

Surface stimulation techniques for bladder management in the spinal dog.

Electrical stimulation of the bladder wall or sacral nerves may be effective for bladder management in the spinal cord injured patient. However, extensive surgery has been required for electrode implantation. We compared urodynamic responses using surface and minimally invasive epidural stimulating techniques in the chronic spinal male dog. Various surface stimulating techniques were effective: 1) sacral monopolar electrical stimulation with negative electrodes over S2 sacral foramina and positive electrodes on the legs, 2) sacral bipolar electrical stimulation with electrodes only over sacral foramina, 3) perineal monopolar electrical stimulation, and 4) perineal tactile stimulation. Urodynamic responses were similar to those for sacral epidural electrodes implanted adjacent to sacral nerves. Voiding was obtained both during stimulation and poststimulation. Stimulating parameters that were effective for daily voiding with sacral surface electrodes were 10 pps, 30 to 45 ma, 0.6 ms pulse duration, and 2 to 5 sec stimulation train duration.