Selective Detrusor Activation By Electrical Sacral Nerve Root Stimulation in Spinal Cord Injury

0022-5347/97/1574-1504$O03.OO~O THE JOURNAL OF UROLOGY

Vol. 157, 1504-1508, April 1997 Printed in 1J.S.A.

Copyright 0 1997 by AMERICAN UROL~CICAL ASS~CIATION, INC

SELECTIVE DETRUSOR ACTIVATION BY ELECTRICAL SACRAL NERVE ROOT STIMULATION IN SPINAL CORD INJURY N. J . M. RIJKHOFF,* H. WIJKSTRA, P. E. V. VAN KERREBROECK

AND

F. M. J. DEBRUYNE

From the Department of Urology, University Hospital Nijmegen, The Netherlands and the Center for Sensory-Motor Interaction, Aalborg University, Denmark

ABSTRACT

Electrical sacral nerve root stimulation can be used in spinal cord injury patients to induce urinary bladder contraction. However, existing stimulation methods activate simultaneously both the detrusor muscle and the urethral sphincter. Urine evacuation is therefore only possible using poststimulus voiding. Micturition would improve if the detrusor muscle could selectively be activated. The purpose of this study was to demonstrate selective detrusor activation in patients by ventral sacral root stimulation. The stimulation method involves selective activation of the small diameter myelinated nerve fibers and consists of a combination of cathodal excitation and selective anodal blocking using a tripolar electrode. To investigate anodal blocking, the intraurethral pressure response to stimulation was measured in acute experiments performed on 12 patients. The influence of both pulse amplitude and pulse duration on the pressure response was analyzed. I n 8 out of 12 patients anodal blocking of somatic motor fibers was possible. This study also indicates the feasibility of selective detrusor activation by sacral root stimulation. KEY WORDS:electrical stimulation. bladder, sacral nerve roots, anodal block

sor. The somatic fibers have a larger caliber than the parasympathetic fibers6 and as large diameter fibers need a smaller stimulus for their activation than smaller ones:. 10 activation of the smaller fibers is always accompanied by activation of the larger fibers. Brindley was the first to describe that, despite the simultaneous contraction of both the detrusor muscle and the urethral sphincter muscle, urine evacuation is possible by taking advantage of differences in the biomechanical characteristics of smooth and striated muscle tissue.” The relaxation time of the striated external urethral sphincter muscle is shorter than the relaxation time of the smooth detrusor muscle so when stimulating with interrupted pulse trains, voiding is achieved between the pulse trains due t o the sustained high intravesical pressure. This poststimulus voiding principle is used in a commercially available system for bladder control (Finetech Medical Ltd., Welwyn Garden City, UK) which has already been implanted in over 700 patients12 with good clinical results.13 However, the stimulus technique has some drawbacks. Poststimulus voiding is an artificial micturition pattern with voiding in spurts at supranormal intravesical pressures. In addition movement of the lower limbs occurs during stimulation as the ventral sacral roots also contain fibers innervating leg musculature. The micturition pattern would improve if the detrusor is selectively activated. Therefore several attempts have been made to prevent the sphincter from contracting. These include La. interruption of the somatic fibers,14.15 blocking the transmission of motor signals through the pudendal nerve,l6.I7and fatiguing the sphincter muscle.’” A better method for selective detrusor activation without extra surgery or additional electrodes would be selective activation of the small diameter parasympathetic fibers in the ventral sacral roots. This is possible when using a selective anodal block.10~l9320 Selective small fiber activation is obtained using a tripolar cuff electrode consisting of a cathode Accepted for publication November 19, 1996. flanked by two anodes (Fig. 1).Near the cathode all fibers * Requests for reprints: Center for Sensory-Motor Interaction, Aalborg University, Fredrik Bajers Vej 7D, Building D-3, 9220 Aalborg, (small and large) are activated while near the distal anode, the propagation of the action potentials (AF”s) in the large Denmark. Supported by grant C92.1249 from the Dutch Kidney Foundation. fibers is blocked by a selective anodal block. The anodal

Normal function of the lower urinary tract is disturbed in patients with spinal cord injury (SCI). In patients with a suprasacral lesion detrusor hyperreflexia and detrusorsphincter dyssynergia develops.’ Hence a number of complications such as poor urine evacuation, urinary tract infections, incontinence, vesicoureteral reflux and hydronephrosis are regularly found in SCI-patients. As restoration of the neural control, e.g. by spinal cord regeneration, is not yet possible, the goal of treatment is to prevent the urological complications while preserving continence. This can be achieved by creating a bladder with large volume, low pressure urine storage and periodic evacuation of urine at low intravesical pressure. Urine evacuation is usually obtained by intermittent catherisation while a hypo- or areflexic bladder is created either by administration of drugs or by detrusor deafferentation. However, many patients are not able to catheterise themselves or are not willing to depend on catheterisation.2 Furthermore, indwelling catheters are a cause of urinary tract infections. I t is therefore desirable to induce voiding by eliciting a detrusor contraction. To induce a detrusor contraction, artificial electrical stimulation through implanted electrodes can be used. Four different sites are available where application of electrical stimuli results in a detrusor contraction: the bladder wall: the pelvic nerves,4 the sacral nerve roots5.6 and the spinal cord.7 The sacral nerve roots appear to be the most attractive stimulation site because the space within the spinal column facilitates mechanically stable electrode positioning and the long intraspinal course of the nerve roots allows application of insulated tripolar electrodes. However, eliciting a detrusor contraction by ventral sacral nerve root stimulation results in co-activation of the urethral closure mechanism leading to little or no voiding. This is due to the composition of the ventral sacral roots, which contain, among others, somatic fibers innervating the external urethral sphincter and preganglionic parasympathetic fibers innervating the detru-

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SELECTIVE DETRUSOR ACTIVATION IN SPINAL CORD INJURY

A-A

X A Selectwe block

1

Smallfiber

1

Largefiber

Excitation

FIG.1. Principle of selective small fiber activation using a tripolar electrode. Both nerve fibergroups (small and large) are excited near &ode. Produced action potentials pro agate away in both tjons, although only propagation in dista? direction has been drawn. Near anodes propagation of action potentials ma be blocked, deriding on amplitude of anodal current and pulse &ration.As large garneter fibers need less current for their blocking than smaller ones, a selective block is possible.

w-

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nental stimulation the l e a d were disconnected h m the itimulator and the normal operation procedure resumed with implantation of the receiver/stimulator. Stimulation and recording. The self-made stimulator consisting of two synchronized current sources with a common cathode was used to drive the tripolar book electrodes. The ratio between the two anodal currents (Fig. 11, which was adjustable, was set to 1 because the electrode configuration is Isymmetrical. Monophasic rectangular pulses without active charge balancing and without the use of a series capacitor were used. Pressure responses were elicited using pulse trains of 3-5 s length, containing identical pulses at a pulse rate of 25 pulseds. As the S3 and 54 ventral roots contain most of the motor fibers innervating the lower urinary tract, experimental stimulation was limited to these two root pairs. As the roots pairs (left and right) were placed in the same electrode groove the bilateral roots were always simultaneoudy stimulated. The toes and feet were visually observed during the experiment to see whether the nerve block reduced the stimulus induced lower limb movements. A two channel transurethral pressure catheter (7F, Gealtec, UK) was used to measure intravesical and intraurethral pressure. The urethral pressure sensor was positioned at the level of the external sphincter so that in response to suprathreshold stimulation, a maximum pressure response was measured. Pressures were sampled at 8 Hz,displayed on a monitor and stored in a portable datalogger. ARer the experiment the data were transferred to a computer for offline analysis. Prior to the stimulation the bladder was filled with approximately 200 ml. saline using a 16-ch traneurethral tilling catheter.

current causes hyperpolarization of the fiber membrane. m e n sufficiently hyperpolarized AP's cannot pass the hyperpolarized zone and are arrested. "he selective blockade is possible since the large diameter fibers need less current for their blocking then smaller fibers.lO.20 As the AP's in the smaller fibers can pass unhindered, the net result is selective small fiber activation. Since the motoneurons innervating the lower limb musculature would also be blocked, this stimulation method would also reduce the stimulation induced lower limb movement. Simulations with a computer model10 showed the theoretical possibilities of this stimulation technique for activation of the detrusor without activation of the urethral sphincter. RESULTS Based on these theoretical results, tripolar cuff electrodes have been developed and successfully tested in acute experAs expected, in all 12 patients toe and foot movements So far, the method of anodal blocking has were recorded and the intravesical and intraurethral preeiments on never been demonstrated in humans. Only Brindley et al. sure increased upon stimulation of at least one sacral root described the use in patients but their paper does not contain pair, using a small duration stimulus pulse (200pa) with a any results apart from the conclusion =wehave not yet suc- sufficient high amplitude (5 mA). This shows that the efferceeded in making the method well enough in patients for ent nemmuscular system was intact and demonstrates the every day use."23 undesired movements of the lower limbs during stimulation. In this study we investigated the feasibility of a selective In 8 patients the stimulation induced movements of toe and anodal block in patients to obtain selective detrusor activa- feet significantly decreased or were complete absent upon tion and determined the effect of pulse amplitude and pulse Stimulation with long duration pulses (700 &, depending on duration on the anodal block. the pulse amplitude, due to the occurrence of an anodal block. This demonstrates that anodal blocking is capable of reducMATERIALS AND METHODS ing the undesired lower limb movements. Fig. 2 shows a typical intravesical and intraurethd presPatient preparation. In acute experiments, measurements were performed on 12 spinal cord injury patients, who un- sure response to stimulation of an S3 root pair for Merent derwent implantation of a Finetech-Brindley sacral anterior pulse amplitudes using a 700 pa pulse duration. The intraroot stimulator. During the operation, access to the intra- vesical and intraurethral pressure responses difFer as the dural sacral nerve roots was gained after a laminedomy. muscle characteristic3 of detrusor and sphincter differ. The Individual nerve roots were identified by their size and by the striated sphincter muscle has a relative fast response to response of several muscle groups to eIectrical stimulation stimulation resulting in a rectangular shaped pressure reusing a hook electrode. The intradural ventral sacral nerve sponse as a function of time (Fig. 2, bottom trace). The roots 6244) were placed in a standard book electrode smooth detrusor muscle has a relative slow respouse resultwhile the dorsal sacral nerve roots ( S W S 5 ) were cut to ing in a slower rise and fall of the pressure response (Fig. 2, abolish the detrusor hypemeflexia. "he book electrode can be top trace).This slow detrusor response to stimulation causes described as contacts mounted in grooves cut into a block of that at a relative high stimulation current (e.g. 6 mA) the insdating silicone rubber. The grooves have a rectanear maximum intravesical pressure is not reached during the cross section of 2 x 3 mm. Each pair of roots (leR and nght) stimulation time and the elicited intravesical pressure dewas placed in a separate groove so that one root pair could be pends largely on the stimulation time (see discussion). The stimulus threshold to elicit a urethral sphincter conStimulated independently from the others. f i r electrode mplantation the operation proceeded with closure of the traction was between 0.1 and 0.2 mk A masimum intraures pressure response is already elicited 0.3 mA and a and tunneling of the electrode leads to a ~ u ~ t a n e o u thral pocket in the flank.Following closure of the skin, the patient further increase of the stimulus to 0.6 and 1.0 mA did not was turned over and the leads were prepared to be Connected result in a larger intraurethral pressure response since aU to the implantable receiver/stimulator. At this time, the leads motoneurons innervating the sphincter are activated and the were connected via an aseptic cable to a self made c0mPute.r maximum obtainable pressure response has been reached. controlled Stimulator and for 15-20 minutes we tested t f Increasing the stimulus above 1.0 mA results in a decrease in modal blocking can be realized. f i r this period of expen- the intraurethd pressure as the current at the distal anode

SELECTIVE DETRUSOR ACTNATION IN SPINAL CORD INJURY

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0'

I 1

2

3

4

5

0

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9

t[m] 6

S

4

6

0

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8

cathodalw e n t [mA]

FIG. 2. IntraureW (Puret) and intravesical (Pblad) pressure RG.3. Inwurethralpressure response (deviation from baseline mot pair for pulse amplitudes pressure) to bhterd stimulation of s3 root PaU 8 8 fundion of between 0.1 and 6.0 mk Each reqmnse was obtamed b applybg c a t h a current. pulee duration: 700 pa; pulse rate: 25 pulseds; stimulw train for ap roximately 5 s ( ulse duration: 7 dpa; p h data from two patienta. rate: 25 pulse&). At p A selective &mmr actantionlapbtruned

reaponsee to stimulation of S3 sacral

t.0

2o"r

as external urethral s p h c t e r does not "8pond to stimulataon(complete block). Stirnulaton with mde p+ resdta in n o d intraurethrd pressure reaponse, emnstratmg that pressure response is not c a d by m d e fatigue or nerve damage.

exceeds the threshold for blocking of the largest somatic motoneurons. W e n increasing the current, more and more fibers are blocked until at 6.0 mA all somatic motoneurons are blocked and the sphincter is prevented from contraction. Although the square shaped sphincter pressure response has disappeared at 6 mA, still an increase in intraurethral pressure was visible. Ae this pressure response has the same shape as the intravesical pressure response it is assumed that the measured intraurethral pressure response is transmitted from the intravesical pressure. This reflection of the intravesical pressure in the intrauretbrd pressure results in two peab in the response to 4.0 mA. The first peak stems from the sphincter contraction while the second one is due to the detrusor contraction. To prove that the reduction of the intraurethral pressure response is caused by anodal bloclting and is not due to other causes such as muscle fatigue or nerve damage, stimulation a t 6.0 mA has also been preformed with a pulse duration of 200 pa. Since 200 pa is usually too short to obtain blocking (see below), the intraurethral pressure response should roughly be the same as the maximum response obtained with 0.6 and 1 mA. F'ig. 2 shows that just by switching the pulse duration between 200 and 700 ps the block could be switched on and off, demonsbating that the urethral pressure response reduction was undoubtedly caused by the anodal block. The stimulus threshold to elicit a detrusor contraction was about 1.6 mA. Beyond the 1.6 mA the intravesical pressure response increases aa more and more parasympathetic motor fibers are activated. At 6.0 mA, 700 pa selective activation of the ddrueor muscle was obtained since the detrusor was activated while there was no square shaped increase in intraurethral pressure. In 8 patients the intraurethral pressure response muld be reduced by anodal blocking. However, in only 2 patients was the recording suf€iciently stable (see Discussion) to measure the relation between pulse parameters and intraurethrd pressure. Fig.3 shows the menimum intraurethrd pressure to stimulation of an 53 root pair aa a function of the cathodal current. Both curves have the same shape. Once the excitation threshold has been exceeded, there is a steep increase in the intraurethral pressure response until all motor fibers have been activated and maximum pressure plateau has' been reached. Beyond the 1-1.5 mA the resmnse gradually decreama as the current at the distal a n d e exceeds t h i

blocking threshold for fibres innervating the sphinc&r. Above 6.0 mA the maximum pressure reduction was reached and no further reduction could be obtained. The occurrence of anodal blocking depends besides on the anodal current also on the puIse duration. The anodal mrrent causes hyperpolarization of the nerve fiber membranes and when sufficiently hyperpolarized, AP's cannot pass the hyperpolarized zone and are arrested. But, as it takes time for an AP to propagate from the excitatiou point (near the cathode) to the hyperpolarized zone, the hyperpolarizing stimulus must at least stay until the AP has reached the hyperpolarized zone. Thus anodal blocking only occurs using a d€icient large pulse duration. To analyze the effect of the pulse duration on the anodal block, the pulse duration was varied while the cathodal current was kept constant at 7.0 mk The maximum intraurethral pressure response as a fuuction of the pulse duration is shown in Fig. 4. Below 200 ps no blocking effects could be observed. When increasing the pulse duration, the preasure response gradually decreased as more and more motoneurons innervating the urethral sphincter are blocked. Above 600 ps the maximum pressure reduction was obtained. Although stable recordings could be obtained in only two patients, the same trends in the relation between pulse parameters and inhiurethral pressure were noted in the other 6 patients in whom anodal blocking could be achieved.

40-

20-

0 0.0

0.1

0.2

0.S

0.4

0.5

0.6

0.7

Pulse duration[ms] FIG. 4. htraurethrd pressure re8 nse (deviation from baseline press?) to bilateral stimulation of g m o t pair as function of pulse d m b o n Cathodal current 7 mA; pulse rate: 25 pulseds; data from twopahents,

SELECTIVE DETRUSOR ACTIVATION IN SPINAL CORD INJURY DISCUSSION

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implant. In acute experiments, stimulating the sacral nerve Both anodal blocking of the large diameter fibers in the mta in dogs using a tripolar cuff electrode (inner diameter: sacral nerve roots19.21.22 and selective detrusor activation 1.5 mm.), Rijkhoff et al. measured initial blocking at 0.3-0.7 by sacral root ~ t i m u l a t i o nhave ~ ~ been demonstrated in ani- mA while a maximum block was obtained at 0.7-1.1 mA.22 mal experiments but have never been demonstrated in man. These relative low currents are caused by the smaller crossThe results of this study demonstrate the feasibility of anod- section of the cuff-electrodes compared to the book electrodes. The pulse duration needed to block the propagation of an ally blocking of the somatic nerve fibres in ventral sacral roots in patients. When used in combination with cathodal induced action potential using a tripolar electrode depends excitation, it results in selective activation of the detrusor on a number of variables including the propagation velocity of the action potential and the distance between the cathode muscle, depending on the pulse parameters. In 4 patients anodal blocking could not be demonstrated. and the anode. Rijkhoff and co-workers simulated the effect This might be due to the more than average mechanical of pulse duration on the blocking thresholds of a 12 pm. fiber manipulation of the nerve roots during identification and using a cufF electrode with 6 mm. contact spacing and found electrode positioning. In comparable animal experiments we a minimum pulse duration of 220 pa for blocking at minimum current while below 155 pa no blocking occurred.10 Experi0 t h noticed that, after excessive manipulation of the nerves, anodal blocking does not occur immediately after mental data on minimum pulse duration for blocking in placement of the electrodes. However, after leaving the elec- animal experiments have been reported by Brindley and trode and nerve untouched, the blocking effects reappears Craggsls and Rijkhoff et al." Brindley and Craggs reported after a few hours. In this study there was about one hour maximum blocking with pulse durations of 0.5 and 1 ms but no blocking at 0.2me when stimulating the sacral roots between electrode placing and stimulation, which could ob- found in baboons.19 In canine experiments Rijkhoff et al. found viously not be extended if blocking did not occur. initial blocking at 150 pa while maximum blocking was obTo evaluate the effect of anodal blocking on the activation tained above 400 pa.22 Compared with these theoretical and of the external urethral sphincter, the intraurethral pressure experimental data the minimum pulse duration for blocking at the level of the urethral sphincter was measured. The in patients (maximum blocking at a pulse duration beyond pressure responses should be stable and reproducible 600 ps) is relative large. The difference is probably due to the throughout the experiment but it proved to be difEcult to lower propagation velocity of the U s in humans as AP ensure complete immobility of the pressure sensor. The cath- propagation velocities in motor fibers are 40% lower man eter tends to move during stimulation and as a result dislo- than in cat and dog.27 cating the intraurethral pressure sensor. This happened in 6 The stimulation time of 3 to 5 s was sufficiently long to patients and the relation between pulse parameters and in- elicit the maximum intraurethral pressure as the contraction traurethral pressure response could not be measured as the time of the striated muscle is less than 0.5 ms. The detrusor setup did not allow for repositioning of the sensors. Therefore muscle contracts more slowly and the stimulation time was in only two patients a stable recording could be obtained. too short to elicit the maximum i n t r a v a i d pressure at 6 However, the occurrence of anodal blocking could also be mA. The stimulation time should have been at about 10 s for observed Visually as an absence of foot or leg movement eliciting a maximum intravesical pressure. Nevertheless the during stimulation. stimulus time was kept relatively short for two reasons. Monophasic rectangular current pulses without active charge Firstly, the intravesical pressure can become very high balancing and without the use of a series capacitor were used. (>250 cm.H,O) which can lead to vesicoureteral reflux. A However, in chronic implants monophasic pulses may induce short stimulus duration reduces this risk. The second reason neural damage and electrode contact corrosion due to a net has to do with the limited time available for the experiment. transfer of electrical charge at each contact. This can be pre- It can take up to 50 s for the intravesical pressure to return vented by adding a secondary reversed pulse. However, during to the baseline pressure when high pressures have been the reversed pulse the anodes become cathodic which causes elicited and this would limit the total number of stimulations excitation if the excitation threshold is exceeded. The reversed during the experiment. current can be kept below excitation threshold when the comThis study shows that the technique of anodal blocking can plete time space between two pulses is used. To avoid the be used in human sacral root stimulation for bladder control. excitation by the reversed pulse, monophasic pulses were used The combination of cathodal excitation and selective anodal exclusively in this study. blocking leads to selective activation of the detrusor muscle. In experiments on anodal blocking of peripheral nerves, In addition to blocking the fibers innervating the urethral excitation of large fibers occurred near the anode at the end sphincter, the large motor fibers innervating muscles in the of a long rectangular blocking pulse.20.26 A gradual decay at lower limbs are also blocked. Hence movement of lower limbs the end of the pulse was necessary to suppress this so-called during stimulation is reduced. When in time this technique anodal break excitation. However, break excitation did not can be used in implanted systems, bladder emptying by MIoccur in our experiments. In animal experiments, we also cral root Stimulation will be more physiological and at lower often observed that anodal blocking was possible without intravesical pressures because the outlet resistance is largely anodal break excitation, using a current just above the block- reduced. ing threshold.22 A further increase of the stimulus usually led break excitation which could be suppressed by a gradual REFERENCES current decrease a t the end of the pulse. It is therefore likely that break excitation will also appear in patients when using 1. Thomas, D. G. and Lucas, M. G.: The urinary tract following rectangular pulses at higher amplitudes. spinal cord iqjury. In: Scientific Foundations of Urology. Edited by G. D. Chisholm and W.R. Fair. Oxford: Heinemann Results of anodal blocking of large diameter nerve fibers Medical Books,3rd edition, chapt. 35, pp. 286-299, 1990. when stimulating the sacral roots of baboons using chronic 2. Lapides, J., Diolmo, A. C.and Silber, S. J.: Clean intermittent implanted book electrodes have been reported by Brindley self catheterisation in the treatment of urinary tract disease. and Craggs.Ig They found initial blocking of fibers innervatJIuroi., 101: 68,1972. ing tail musculature a t 4.5 m~ while at 9.0 m~ a complete 3. Maeasi. P. and Simon, Z.:Electrical stimulation of the bladder block was obtained. These currents are roughly twice as large &d &avidity. Uml..Int., 41: 241, 1986. compared to our results. The discrepancy may be caused by a 4. Kaekenbeeck. B.: Electmstimulation de la vessie des paralarger cross-section of their electrode or bv the connective pl6giques. Technique de Burghele-Ichim-Demet. A d a Urol. Belg., 47: 139, 1979. tissue between the contacts and the nerve r&ts in the chronic

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5. Brindley, G. S., Polkey, C. E., Rushton, D. N. and Cardozo, L.:

Sacral anterior root stimulators for bladder control in paraplegia: the first 50 cases. J . Neurol. Neurosurg. Psych., 49: 1104, 1986.

6. Tanagho, E. A,, Schmidt, R. A. and Orvis, B. R.: Neural stimulation for control of voiding dysfunction: a preliminary report in 22 patients with serious neuropathic voiding disorders. J . Urol., 142 340, 1989. 7. Grimes, J . H. and Nashold, B. S.: Clinical application of electronic bladder stimulation in paraplegics. Br. J . Urol., 46:653, 1974. 8. Schalow, G. and Barth, H.: Group conduction velocities and nerve fibre diameters of a and y-motoneurons from lower

sacral nerve roots of the dog and humans. Gen. Physiol. Bioph., 11:85, 1992. 9. Blair. E. and Erlanger, J.: A comparison of the characteristics of axons through their individual electrical responses. Am. J . Physiol., 106:524, 1933. 10. Rijkhoff, N. J. M., Holsheimer, J., Koldewijn, E. L., Struijk, J. J., van Kerrebroeck, P. E. V., Debruyne, F. M. J.and Wijkstra, H.: Selective stimulation of sacral nerve roots for bladder control; A study by computer modeling. IEEE Trans. Biomed. Eng., 41: 413, 1994. 11. Brindley, G. S.: Emptying the bladder by stimulating the sacral ventral root. J . Physiol., 237: 15, 1973. 12. Creasey, G. H.: Electrical stimulation of the sacral roots for micturition after spinal cord injury. Urol. Clin. North Am., 2 0 505, 1993. 13. Brindley, G. S.: The first 500 patients with sacral anterior root stimulator implants: general description. Paraplegia, 3 2 795, 1994. 14. Hohenfellner, M., Paick, J.-S., Trigo-Rocha, F., Schmidt, R. A,,

Kaula, N. F., Thuroff, J . W. and Tanagho, E. A,: Site of deafferentation and electrode placement for bladder stimulation: clinical implications. J. Urol., 147: 1665, 1992. 15. Schmidt, R. A., Bruschini, H. and Tanagho, E. A.: Sacral root stimulation in controlled micturition (DeriDheral somatic neurotomy and stimulated voiding). Invest. Urol., 17: 130, 1979. 16. Ishigooka, M., Hashimoto, T., Sasagawa, I., Izumiya, K. and

Nakada, T.: Modulation of the urethral pressure by high. frequency block stimulus in dogs. Eur. Urol., 25: 334, 1994, 17. Sweeney, J. D., Mortimer, J. T. and Bodner, D. R.: Acute animal studies on electrically induced collision block of pudendal nerve motor activity. Neurourol. Urodynam., 8: 521, 1989. 18. Li, J.-S.,Hassouna, M., Sawan, M., Duval, F. and Elhilali, M. M.: Electrical stimulation induced sphincter fatigue during voiding. J . Urol., 148:949, 1992. 19. Brindley, G. S. and Craggs, M. D.: A technique for anodally blocking large nerve fibers through chronically implanted electrodes. J. Neurol. Neurosurg. Psych., 43: 1083, 1980. 20. Fang, Z.-P. and Mortimer, J. T.: Selective activation of small motor axons by quasitrapezoidal current pulses. IEEE Trans. Biomed. Eng., 3 8 168, 1991. 21. Koldewijn, E. L., Rijkhoff, N. J . M., van Kerrebroeck, P. E. v., Debruyne, F. M. J . and Wijkstra, H.: Selective sacral root stimulation for bladder control: acute experiments in an animal model. J. Urol., 151: 1674, 1994. 22. Rijkhoff, N. J. M., Koldewijn, E. L., van Kerrebroeck, P. E. V., Debruyne, F. M. J . and Wijkstra, H.: Acute animal studies on the use of a n anodal block to reduce urethral resistance in sacral root stimulation. IEEE Trans. Rehab. Eng., 2: 92, 1994. 23. Brindley, G. S., Polkey, C. E. and Rushton, D. N.: Sacral anterior root stimulators for bladder control in paraplegia. Paraplegia, 2 0 365, 1982. 24. Brindley, G. S.: An implant to empty the bladder or close the urethra. J . Neurol. Neurosurg. Psych., 4 0 358, 1977. 25. Rijkhoff, N. J. M., Koldewijn, E. L., van Kerrebroeck, P. E. V.,

Debruyne, F. M. J . and Wijkstra, H.: Selective activation of the detrusor muscle by sacral root stimulation in a canine model. Neurourol. Urodyn., 12:381, 1993. 26. van den Honert, C. and Mortimer, J . T.: A technique for collision block of peripheral nerve: single stimulus analysis. IEEE Trans. Biomed. Eng., 28: 373, 1981. 27. Schalow, G., Bersch, U., Gocking, K. and Zach, G. A.: Detrusorsphincteric dyssynergia in paraplegics compared with the synergia in a braindead human by using the single-fibre action potential recording method. J . Autonom. Nerv. Syst., 52: 151, 1995.