Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
PDF hosted at the Radboud Repository of the Radboud University Nijmegen The following full text is a publisher's version. For additional information about this publication click this link. http://hdl.handle.net/2066/24869 Please be advised that this information was generated on 2017-06-15 and may be subject to change. 0022-5347/97/1574«1504$03.00/0 Vol. 157, 1504-1508, April 1997 Printed in U.S.A. T h e J o u r n a l o f U ro lo g y Copyright © 1997 by A m e r i c a n U r o l o g i c a l A s s o c i a t i o n , I n c 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. In 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 W ords: electrical stimulation, bladder, sacral nerve roots, anodal block sor. The somatic fibers have a larger caliber than the para sympathetic fibers8 and as large diameter fibers need a smaller stimulus for their activation than smaller ones,9»10 activation of the smaller fibers is always accompanied by activation of the larger fibers. Brindley was the first to describe that, despite the simul taneous contraction of both the detrusor muscle and the urethral sphincter muscle, urine evacuation is possible by taking advantage of differences in the biomechanical charac teristics of smooth and striated muscle tissue.11 The relax ation 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 to the sus tained high intravesical pressure. This poststimulus voiding principle is used in a commercially available system for blad der 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 in clude i.a. interruption of the somatic fibers,14»16 blocking the transmission of motor signals through the pudendal nerve,16-17 and fatiguing the sphincter muscle.18 A better method for selective detrusor activation without extra surgery or additional electrodes would be selective ac tivation of the small diameter parasympathetic fibers in the ventral sacral roots. This is possible when using a selective anodal block.10»19>20 Selective small fiber activation is ob tained 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, Aal (small and large) are activated while near the distal anode, borg University, Fredrik Bajers Vej 7D, Building D-3, 9220 Aalborg, the propagation of the action potentials (AP’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.1 Hence a number of compli cations such as poor urine evacuation, urinary tract infec tions, 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 pres sure urine storage and periodic evacuation of urine at low intravesical pressure. Urine evacuation is usually obtained by intermittent catherisation while a hypo- or areflexic blad der is created either by administration of drugs or by detru sor 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. It is therefore desirable to induce voiding by eliciting a detrusor contraction. To induce a detrusor contraction, artificial electrical stim ulation through implanted electrodes can be used. Four dif ferent sites are available where application of electrical stim uli results in a detrusor contraction: the bladder wall,3 the pelvic nerves,4 the sacral nerve roots5’6 and the spinal cord.7 The sacral nerve roots appear to be the most attractive stim ulation site because the space within the spinal column fa cilitates 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- 1504 SELECTIVE DETRUSOR ACTIVATION IN SPINAL CORD INJURY n h JT 12 Bladder Anode A. Sphincter Mr X Mr Cathode K K Anode 3 Small fiber 3 Large fiber Selective block Excitation F ig . 1. Principle of selective small fiber activation using a tripolar electrode. Both nerve fiber groups (small and large) are excited near cathode. Produced action potentials propagate away in both direc tions, although only propagation in distal direction has been drawn. Near anodes propagation of action potentials may be blocked, de pending on amplitude of anodal current and pulse duration. As large diameter fibers need less current for their blocking than smaller ones, a selective block is possible. current causes hyperpolarization of the fiber membrane. When sufficiently hyperpolarized AP’s cannot pass the hy perpolarized zone and are arrested. The selective blockade is possible since the large diameter fibers need less current for their blocking then smaller fibers.10-20 As the AP’s in the smaller fibers can pass unhindered, the net result is selective small fiber activation. Since the motoneurons inner vating 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 theoret ical possibilities of this stimulation technique for activation of the detrusor without activation of the urethral sphincter. Based on these theoretical results, tripolar cuff electrodes have been developed and successfully tested in acute exper iments on dogs.21,22 So far, the method of anodal blocking has never been demonstrated in humans. Only Brindley et al. described the use in patients but their paper does not contain any results apart from the conclusion “we have not yet suc ceeded in making the method well enough in patients for every day use.”23 In this study we investigated the feasibility of a selective anodal block in patients to obtain selective detrusor activa tion and determined the effect of pulse amplitude and pulse duration on the anodal block. MATERIALS AND METHODS Patient preparation. In acute experiments, measurements were performed on 12 spinal cord injury patients, who un derwent implantation of a Finetech-Brindley sacral anterior root stimulator. During the operation, access to the intra dural sacral nerve roots was gained after a laminectomy. Individual nerve roots were identified by their size and by the response of several muscle groups to electrical stimulation using a hook electrode. The intradural ventral sacral nerve roots (S2-S4) were placed in a standard book electrode24 while the dorsal sacral nerve roots (S2-S4/S5) were cut to abolish the detrusor hyperreflexia. The book electrode can be described as contacts mounted in grooves cut into a block of insulating silicone rubber. The grooves have a rectangular cross section of 2 X 3 mm. Each pair of roots (left and right) was placed in a separate groove so that one root pair could be stimulated independently from the others. After electrode implantation the operation proceeded with closure of the dura and tunneling of the electrode leads to a subcutaneous pocket in the flank. Following closure of the skin, the patient was turned over and the leads were prepared to be connected to the implantable receiver/stimulator. At this time, the leads were connected via an aseptic cable to a self made computer controlled stimulator and for 15-20 minutes we tested if anodal blocking can be realized. After this period of experi- 1505 mental stimulation the leads were disconnected from the stimulator and the normal operation procedure resumed with implantation of the receiver/stimulator. Stimulation and recording. The self-made stimulator con sisting 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. 1), which was adjustable, was set to 1 because the electrode configuration is symmetrical. 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 pulses/s. As the S3 and S4 ventral roots contain most of the motor fibers innervating the lower uri nary 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 simultaneously 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. After the experiment the data were transferred to a computer for off line analysis. Prior to the stimulation the bladder was filled with approximately 200 ml. saline using a 16-ch transure thral filling catheter. RESULTS As expected, in all 12 patients toe and foot movements were recorded and the intravesical and intraurethral pres sure increased upon stimulation of at least one sacral root pair, using a small duration stimulus pulse (200 / a s ) with a sufficient high amplitude (5 mA), This shows that the effer ent neuromuscular system was intact and demonstrates the undesired movements of the lower limbs during stimulation. In 8 patients the stimulation induced movements of toe and feet significantly decreased or were complete absent upon stimulation with long duration pulses (700 ¡is), depending on the pulse amplitude, due to the occurrence of an anodal block. This demonstrates that anodal blocking is capable of reduc ing the undesired lower limb movements. Fig. 2 shows a typical intravesical and intraurethral pres sure response to stimulation of an S3 root pair for different pulse amplitudes using a 700 /xs pulse duration. The intra vesical and intraurethral pressure responses differ as the muscle characteristics of detrusor and sphincter differ. The striated sphincter muscle has a relative fast response to stimulation resulting in a rectangular shaped pressure re sponse as a function of time (Fig. 2, bottom trace). The smooth detrusor muscle has a relative slow response result ing in a slower rise and fall of the pressure response (Fig. 2, top trace). This slow detrusor response to stimulation causes that at a relative high stimulation current (e.g. 6 mA) the maximum intravesical pressure is not reached during the stimulation time and the elicited intravesical pressure de pends largely on the stimulation time (see discussion). The stimulus threshold to elicit a urethral sphincter con traction was between 0.1 and 0.2 mA. A maximum intraure thral pressure response is already elicited 0.3 mA and a farther increase of the stimulus to 0.5 and 1.0 mA did not result in a larger intraurethral pressure response since all motoneurons innervating the sphincter are activated and the maximum obtainable pressure response has been reached. Increasing the stimulus above 1.0 mA results in a decrease in the intraurethral pressure as the current at the distal anode 1506 SELECTIVE DETRUSOR ACTIVATION IN SPINAL CORD INJURY o<N E ü , CL) l- r 3 æ e PM 6 CD u. e >5 o 1 8 6 Cathodal current [mA] Fig. 2. Intraurethral (Puret) and intravesical (Pblad) pressure responses to stimulation of S3 sacral root pair for pulse amplitudes between 0.1 and 6.0 mA. Each response was obtained by applying stimulus train for approximately 5 s (pulse duration^ 700 /xs; pulse rate: 25 pulses/s). At 6.0 mA selective detrusor activation is obtained as external urethral sphincter does not respond to stimulation (com plete block). Stimulation with 200 fxs wide pulses results in normal intraurethral pressure response, demonstrating that pressure re sponse is not caused by muscle fatigue or nerve damage. exceeds the threshold for blocking of the largest somatic motoneurons. When 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. As this pressure response has the same shape as the intravesical pressure response it is assumed that the measured intraurethral pressure response is trans mitted from the intravesical pressure. This reflection of the intravesical pressure in the intraurethral pressure results in two peaks 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 blocking and is not due to other causes such as muscle fatigue or nerve damage, stimulation at 6.0 mA has also been preformed with a pulse duration of 200 /¿s. Since 200 jus is usually too short to obtain blocking (see below), the intraurethral pressure response should roughly be the same as the maximum response obtained with 0.5 and 1 mA. Fig. 2 shows that just by switching the pulse duration between 200 and 700 jlls the block could be switched on and off, demonstrating that the urethral pressure re sponse reduction was undoubtedly caused by the anodal block. The stimulus threshold to elicit a detrusor contraction was about 1.5 mA. Beyond the 1.5 mA the intravesical pressure response increases as more and more parasympathetic motor fibers are activated. At 6.0 mA, 700 jus selective activation of the detrusor muscle was obtained since the detrusor was activated while there was no square shaped increase in in traurethral pressure. In 8 patients the intraurethral pressure response could be reduced by anodal blocking. However, in only 2 patients was the recording sufficiently stable (see Discussion) to measure the relation between pulse parameters and intraurethral pressure. Fig. 3 shows the maximum intraurethral pressure to stimulation of an S3 root pair as a function of the cathodal current. Both curves have the same shape. Once the excita tion 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 response gradually decreases as the current at the distal anode exceeds the F ig. 3. Intraurethral pressure response (deviation from baseline pressure) to bilateral stimulation of S3 root pair as function o: cathodal current. Pulse duration: 700 ju,s; pulse rate: 25 pulses/s data from two patients. blocking threshold for fibres innervating the sphincter, 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 pulse duration. The anodal cur rent causes hyper polarization 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 excitation 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 sufficient 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 mA. The maximum intraurethral pressure response as a function of the pulse duration is shown in Fig. 4. Below 200 jus no blocking effects could be observed. When increasing the pulse duration, the pressure response gradually decreased as more and more motoneurons innervating the urethral sphincter are blocked. Above 600 ¡is the maximum pressure reduction was obtained. Although stable recordings could be obtained in only two patients, the same trends in the relation between pulse pa rameters and intraurethral pressure were noted in the other 6 patients in whom anodal blocking could be achieved. O 1 <u C/3 w PU J3 <U § h Ih >S 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 Pulse duration [ms] Fig. 4. Intraurethral pressure response (deviation from baseline pressure) to bilateral stimulation of S3 root pair as function of pulse duration. Cathodal current: 7 mA; pulse rate: 25 pulses/s; data from two patients. SELECTIVE DETRUSOR ACTIVATION IN SPINAL CORD INJURY DISCUSSION Both anodal blocking of the large diameter fibers in the sacral nerve roots19,21,22 and selective detrusor activation by sacral root stimulation25 have been demonstrated in ani mal experiments but have never been demonstrated in man. The results of this study demonstrate the feasibility of anodally blocking of the somatic nerve fibres in ventral sacral roots in patients. When used in combination with cathodal excitation, it results in selective activation of the detrusor muscle, depending on the pulse parameters. In 4 patients anodal blocking could not be demonstrated. This might be due to the more than average mechanical manipulation of the nerve roots during identification and electrode positioning. In comparable animal experiments we often noticed that, after excessive manipulation of the nerves, anodal blocking does not occur immediately after placement of the electrodes. However, after leaving the elec trode and nerve untouched, the blocking effects reappears after a few hours. In this study there was about one hour between electrode placing and stimulation, which could ob viously not be extended if blocking did not occur. To evaluate the effect of anodal blocking on the activation of the external urethral sphincter, the intraurethral pressure at the level of the urethral sphincter was measured. The pressure responses should be stable and reproducible throughout the experiment but it proved to be difficult to ensure complete immobility of the pressure sensor. The cath eter tends to move during stimulation and as a result dislo cating the intraurethral pressure sensor. This happened in 6 patients and the relation between pulse parameters and in traurethral pressure response could not be measured as the setup did not allow for repositioning of the sensors. Therefore in only two patients a stable recording could be obtained. However, the occurrence of anodal blocking could also be observed visually as an absence of foot or leg movement during stimulation. Monophasic rectangular current pulses without active charge balancing and without the use of a series capacitor were used. However, in chronic implants monophasic pulses may induce neural damage and electrode contact corrosion due to a net transfer of electrical charge at each contact. This can be pre vented by adding a secondary reversed pulse. However, during the reversed pulse the anodes become cathodic which causes excitation if the excitation threshold is exceeded. The reversed current can be kept below excitation threshold when the com plete time space between two pulses is used. To avoid the excitation by the reversed pulse, monophasic pulses were used exclusively in this study. In experiments on anodal blocking of peripheral nerves, excitation of large fibers occurred near the anode at the end of a long rectangular blocking pulse.20»26 A gradual decay at the end of the pulse was necessary to suppress this so-called anodal break excitation. However, break excitation did not occur in our experiments. In animal experiments, we also often observed that anodal blocking was possible without anodal break excitation, using a current just above the block ing threshold.22 A further increase of the stimulus usually led to break excitation which could be suppressed by a gradual current decrease at the end of the pulse. It is therefore likely that break excitation will also appear in patients when using rectangular pulses at higher amplitudes. Results of anodal blocking of large diameter nerve fibers when stimulating the sacral roots of baboons using chronic implanted book electrodes have been reported by Brindley and Craggs.19 They found initial blocking of fibers innervat ing tail musculature a tt4.5 mA while at 9.0 mA a complete block was obtained. These currents are roughly twice as large compared to our results. The discrepancy may be caused by a larger cross-section of their electrode or by the connective tissue between the contacts and the nerve roots in the chronic 1507 implant. In acute experiments, stimulating the sacral nerve roots in dogs using a tripolar cuff electrode (inner diameter: 1.5 mm.), Rijkhoff et al. measured initial blocking at 0.3-0.7 mA while a maximum block was obtained at 0,7-1.1 mA.22 These relative low currents are caused by the smaller crosssection of the cuff-electrodes compared to the book electrodes. The pulse duration needed to block the propagation of an induced action potential using a tripolar electrode depends on a number of variables including the propagation velocity of the action potential and the distance between the cathode and the anode. Rijkhoff and co-workers simulated the effect of pulse duration on the blocking thresholds of a 12 fxm. fiber using a cuff electrode with 6 mm. contact spacing and found a minimum pulse duration of220 ¡is for blocking at minimum current while below 155 /xs no blocking occurred.10 Experi mental data on minimum pulse duration for blocking in animal experiments have been reported by Brindley and Craggs19 and Rijkhoff et al.22 Brindley and Craggs reported maximum blocking with pulse durations of 0.5 and 1 ms but found no blocking at 0.2 ms when stimulating the sacral roots in baboons.19 In canine experiments Rijkhoff et al. found initial blocking at 150 /xs while maximum blocking was ob tained above 400 ¡is .22 Compared with these theoretical and experimental data the minimum pulse duration for blocking in patients (maximum blocking at a pulse duration beyond 600 /xs) is relative large. The difference is probably due to the lower propagation velocity of the AP’s in humans as AP propagation velocities in motor fibers are 40% lower man than in cat and dog.27 The stimulation time of 3 to 5 s was sufficiently long to elicit the maximum intraurethral pressure as the contraction time of the striated muscle is less than 0.5 ms. The detrusor muscle contracts more slowly and the stimulation time was too short to elicit the maximum intravesical pressure at 6 mA. The stimulation time should have been at about 10 s for eliciting a maximum intravesical pressure. Nevertheless the stimulus time was kept relatively short for two reasons. Firstly, the intravesical pressure can become very high (>250 cm. H20) which can lead to vesicoureteral reflux. A short stimulus duration reduces this risk. The second reason has to do with the limited time available for the experiment. It can take up to 50 s for the intravesical pressure to return to the baseline pressure when high pressures have been elicited and this would limit the total number of stimulations during the experiment. This study shows that the technique of anodal blocking can be used in human sacral root stimulation for bladder control. The combination of cathodal excitation and selective anodal blocking leads to selective activation of the detrusor muscle. In addition to blocking the fibers innervating the urethral sphincter, the large motor fibers innervating muscles in the lower limbs are also blocked. Hence movement of lower limbs during stimulation is reduced. When in time this technique can be used in implanted systems, bladder emptying by sa cral root stimulation will be more physiological and at lower intravesical pressures because the outlet resistance is largely reduced. REFERENCES 1. Thomas, D. G. and Lucas, M. G.: The urinary tract following spinal cord injury. In: Scientific Foundations of Urology. Ed ited by G. D. Chisholm and W. R. Fair. Oxford: Heinemann Medical Books, 3rd edition, chapt. 35, pp. 286-299, 1990. 2 . Lapides, J., Diokno, A. C. and Silber, S. J.: Clean intermittent self catheterisation in the treatment of urinary tract disease. J. Urol., 107: 458, 1972. 3. Magasi, P. and Simon, Z.: Electrical stimulation of the bladder and gravidity. Urol. Int., 41: 241, 1986. 4. Kaekenbeeck, B.: Electrostimulation de la vessie des para plégiques. Technique de Burghele-Ichim-Demetrescu. Acta Urol. Belg., 47: 139, 1979. 1508 SELECTIVE DETRUSOR ACTIVATION IN SPINAL CORD INJURY 5. Brindley, G. S., Polkey, C. E., Rushton, D. N. and Cardozo, L.: Sacral anterior root stimulators for bladder control in paraple gia: the first 50 cases. J. Neurol. Neurosurg. Psych., 49:1104, 1986. 6 . Tanagho, E. A., Schmidt, R. A. and Orvis, B. R.: Neural stimu lation 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 elec tronic 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 7 -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., 20: 505, 1993. 13. Brindley, G. S.: The first 500 patients with sacral anterior root stimulator implants: general description. Paraplegia, 32: 795, 1994. 14. Hohenfellner, M., Paick, J.-S., Trigo-Rocha, F., Schmidt, R. A., Kaula, N. F., Thtiroff, 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 (peripheral somatic neu rotomy and stimulated voiding). Invest. Urol., 17: 130, 1979. 16. Ishigooka, M., Hashimoto, T,} Sasagawa, I., Izumiya, K. and 17. 18. 19. 20. 21 . 22 . 23. 24. 25. 26. 27. Nakada, T.: Modulation of the urethral pressure by highfrequency block stimulus in dogs. Eur. Urol., 25; 334, 1994. 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. Li, J.-S., Hassouna, M., Sawan, M., Duval, F. and Elhilali, M. M.: Electrical stimulation induced sphincter fatigue during void ing. J. Urol., 148: 949, 1992. Brindley, G. S. and Craggs, M. D.: A technique for anodally blocking large nerve fibers through chronically implanted elec trodes. J. Neurol. Neurosurg. Psych., 43: 1083, 1980. Fang, Z.-P. and Mortimer, J. T.: Selective activation of small motor axons by quasitrapezoidal current pulses. IEEE Trans. Biomed. Eng., 38: 168, 1991. Koldewijn, E. L., Rijkhoff, N. J. M., van Kerrebroeck, P. E. V ,3 Debruyne, F. M. J. and Wijkstra, H.: Selective sacral root stimulation for bladder control: acute experiments in an ani mal model. J. Urol., 151: 1674, 1994. 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 an anodal block to reduce urethral resistance in sacral root stimulation. IEEE Trans. Rehab. Eng., 2 : 92,1994. Brindley, G. S., Polkey, C. E. and Rushton, D. N.: Sacral anterior root stimulators for bladder control in paraplegia. Paraplegia, 20: 365, 1982. Brindley, G. S.: An implant to empty the bladder or close the urethra. J. Neurol. Neurosurg. Psych., 40: 358, 1977. 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. 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. 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.