James S. Walter

Bladder Inhibition by Penile Nerve Stimulation in Spinal Cord Injury Patients

Detrusor hyperreflexia causing voiding dysfunction in spinal cord injury patients is a difficult problem and is not always treated effectively by anticholinergic agents. We have been investigating electrical stimulation methods to inhibit hyperreflexia and dorsal penile nerve stimulation is the most promising. Six chronic suprasacral spinal cord injury men (average age 36 years) underwent stimulation testing with water cystometry before, during and after stimulation. Dorsal penile stimulation was done with carbon rubber butterfly electrodes (Medtronic) with parameters of 5 pulses per second, 0.35 msec. pulse duration, and current at a level above the threshold for pelvic twitching activity and adjusted for optimal bladder effect (range 25 to 70 mamp.). In all 6 patients the cystometrogram during stimulation showed an increase in bladder volume over the prestimulation cystometrogram (range 27 to 150%). In 2 patients there was no detrusor activity after filling to 500 cc. Stimulation was then stopped and a spontaneous contraction occurred. The cystometrogram conducted after the stimulus also had less volume than that performed during stimulation but it was larger than the prestimulation volume. Penile nerve stimulation was painless with no side effects. Penile nerve electrical stimulation is effective for inhibiting bladder hyperreflexia and should be easily adaptable for chronic home use as an alternative to current therapy.

The effect of electrical stimulation on colonic transit following spinal cord injury in cats.

The effect of direct electrical stimulation on colinic transit and manometric recordings following spinal cord injury were assessed in five adult male cats. Intra-colonic catheters were surgically placed, stimulating electrodes were sutured to the colonic serosa and a laminectomy with spinal cord clamping at a T4 level was done to induce spinal cord injury (SCI). Twenty radiopaque markers were inserted through an intra-colonic catheter located 1 cm distal to the cecum and were monitored with daily fluoroscopy as a measure of colonic transit. Transit measurements were compared before SCI, after SCI and after SCI with electrical stimulation of 40 pps, 1 ms, and 0–50 mA. Colonic transit following SCI was significantly prolonged (P<0.05) when compared to the transit before SCI. Electrical stimulation following SCI improved colonic transit to values not significantly different from those before SCI. Spontaneous colonic phasic motor activity was similar both before and after SCI. Manometric defection patterns were also observed to be similar before SCI and after SCI with electrical stimulation. Based on our scoring criteria, the most frequent response to electrical stimulation was an abdominal contraction. These findings demonstrate that colonic transit is prolonged following SCI and that direct electrical stimulation of the colon following SCI improves colonic transit in an animal model.

Diaphragm and accessory respiratory muscle stimulation using intramuscular electrodes

We tested the hypothesis that electrical stimulation of respiratory muscles can be obtained from intramuscular electrodes. In acute anesthetized dogs, suture-type intramuscular electrodes were placed in each hemidiaphragm and needle electrodes were placed in various intercostal regions of the thorax. During a hyperventilation induced period of apnea a 2-second stimulation was applied to the diaphragm or to the thoracic electrodes, followed by a combined thoracic-diaphragm stimulation period. Thoracic expansion and tidal volumes were measured as indices of inspiratory effort. We found that diaphragm stimulation produced tidal volumes between 104% and 180% of spontaneous breathing. Electrodes in the upper thorax produced chest expansion and when combined with diaphragm stimulation increased tidal volumes (p < .05). We conclude that intramuscular electrodes represent a feasible method for long-term electrogenic ventilation. Also, thoracic support for diaphragm pacing in quadriplegics could produce a more effective long-term system that is less prone to fatigue and failure.

Botulinum Toxin Injections for Voiding Dysfunction Following SCI

Botulinum toxin (BT) injections have been used successfully to treat spastic muscle conditions, including detrusor-sphincter dyssynergia (DSD) seen in spinal cord injury (SCI) patients. In our urology clinic, we used BT to treat three SCI patients who had voiding dysfunction, using a transperineal needle with electromyographic (EMG) monitoring. Two of the patients reported excellent results following the treatment. One patient, with whom the staff had difficulty doing intermittent catheterization (IC), improved significantly. The other patient had improved voiding with an external catheter and minimal urinary residual. The third patient had no improvement of leg spasms with his voiding dysfunction and required a sphincterotomy. Although patients may need repeat injections, BT is minimally invasive and easy to administer with no side effects. Overall, BT injection is an excellent method of managing voiding in SCI patients, especially those on continuous external catheters and with IC management who refuse or are not good candidates for surgery.

Female urinary retention

The urodynamic results in 68 females with urinary retention were reviewed. There were two groups: 39 patients with neurologic causes for retention, and 29 patients in whom possible causes for retention included: psychological history (15 patients), gynecologic pathology, and urinary tract infection. Nine patients in the neurogenic group and 13 patients in the non-neurogenic group had undergone urethral dilatation with no improvement. Upper urinary tract evaluation was unremarkable. Detrusor failure was the prominent bladder pattern in both groups. In the neurogenic group, low pressure detrusor activity was also present in 10 patients, 3 of whom had sphincter dyssynergia. Flow rate, surface electromyography, and bethanechol supersensitivity test could not help differentiate neurogenic from non-neurogenic detrusor failure. The notation of abnormal bladder sensation did significantly differ between the groups, but was of limited accuracy as an indicator of neurogenic retention. Self-intermittent catheterization was the most effective treatment for both groups, with some patients voiding adequately in follow-up. Although no one test can accurately differentiate neurogenic from nonneurogenic female urinary retention, careful neurourologic evaluation will help guide us to more appropriate management.

Hypomagnesemia in Hemodialysis Patients: Role of Proton Pump Inhibitors

Background: Recent observations have associated hypomagnesemia with increased risk of cardiovascular morbidity and mortality in hemodialysis patients. Methods: We did a 3-month chart review of 62 chronic hemodialysis patients at a single US hospital. All were dialyzed using a dialysate [Mg] of 0.75-1.0 mEq/l. Patients were divided into two groups: hypomagnesemic (mean predialysis plasma [Mg] <1.5 mEq/l) and non-hypomagnesemic (mean predialysis plasma [Mg] ≥1.5 mEq/l). Results: All patients were male; mean age was 64.3 ± 8.7 years and the majority (73%) diabetic. 24 patients (39%) had hypomagnesemia and 38 (61%) were not hypomagnesemic. There were no significant differences between the two groups in age, diabetes status, blood pressure, duration of dialysis, plasma calcium, phosphorus, albumin, intact parathyroid hormone (PTH), dialysis adequacy (Kt/V), or dietary protein intake (as estimated by normalized protein catabolic rate, nPCR). However, use of proton pump inhibitors (PPIs) was significantly associated with hypomagnesemia (plasma [Mg] 1.48 ± 0.16 mEq/l in the PPI group vs. 1.65 ± 0.26 mEq/l in the non-PPI group, p = 0.007). Adjustment for age, diabetes status, duration of dialysis, plasma albumin, Kt/V, nPCR, and diuretic use did not affect the association between PPI use and hypomagnesemia. Conclusions: Use of PPIs in patients dialyzed using a dialysate [Mg] of 0.75-1.0 mEq/l is associated with hypomagnesemia. We suggest monitoring plasma [Mg] in patients taking PPIs, with discontinuation of the medication if possible and/or adjustment of dialysate [Mg] to normalize plasma [Mg].

Comparison of direct bladder and sacral nerve stimulation in spinal cats

Neuroprosthetic techniques have been used to facilitate voiding via electrical stimulation for bladder management following spinal cord injury (SCI), but high urethral resistance has been a problem. This problem was investigated here in the chronic, spinal, male cat (C6-T1) using direct bladder and sacral nerve stimulation. Direct bladder stimulation was only conducted during terminal procedures with an open abdomen and with four hook electrodes inserted into the bladder wall. Sacral stimulation was conducted daily during the 10 weeks post-SCI and during terminal procedures. Stimulation was conducted with both implanted epidural electrode and surface electrodes over the sacral bone. Both of these sacral methods stimulated anterior and posterior roots. However, these sacral methods were generally ineffective for inducing voiding during the study. In three of the five animals investigated, stimulation did not empty the bladder. In the remaining two animals, the bladder was emptied with sacral stimulation, but only after return of bladder reflex activity, 2 to 4 weeks post-injury. When poor voiding occurred in spite of high bladder pressures, it indicates high urethral resistance. This was confirmed using video cystourethrography where the membranous urethra was observed to remain closed following stimulation. Direct bladder stimulation was then compared to sacral nerve stimulation during terminal procedures. Direct bladder stimulation induced voiding at a high rate both during and after stimulation, whereas sacral nerve stimulation with implanted electrodes induced voiding at a lower rate and only after stimulation. A simple urethral resistance measure, the ratio of bladder pressure to voiding rate, was lower with direct bladder stimulation than sacral nerve stimulation. Stimulation-facilitated voiding has also been associated with the development of bladder wall hypertrophy. This problem was investigated by evaluating bladder wall thickness postmortem in three groups of animals: the first group was the spinal-stimulated animals detailed above; the additional two groups were a spinal-nonstimulated but instrumented group maintained for 10 weeks following injury, and an intact group of animals. The stimulated spinal cats tended to have the thickest bladder wall followed by the nonstimulated spinal cats. The wall thickness of intact animals served as a control.

Idiopathic anejaculation treated by vibratory stimulation

Idiopathic anejaculation is a rare cause of infertility usually treated by psychotherapy. However, electrovibration may be a simple, noninvasive adjunct to the treatment of this disorder. In our two cases, we obtained ejaculate adequate for insemination in one patient and noted some gain in orgasmic sensation in the other. The success in these two infertile patients who had already undergone lengthy psychotherapy is promising. Nevertheless, psychotherapy will continue to be the standard of therapy until we have more experience with penile electrovibration.

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 animals 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.

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.