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EXTRADURAL COLD BLOCK FOR SELECTIVE NEUROSTIMULATION OF THE BLADDER: DEVELOPMENT OF A NEW TECHNIQUE
0022-5347/99/1613-0950$03.00/0 'h!S
Vol. 161,950-954,March 1999 Printed in U.S.A.
JOURNAL OF UROLOGY
Copyright @ 1999 by AMERICm
UROLoClCAL kssocLsTlON,
INC.
EXTRADURAL COLD BLOCK FOR SELECTIVE NEUROSTIMULATION OF THE BLADDER: DEVELOPMENT OF A NEW TECHNIQUE STEFAN SCHUMACHER,* STEPHAN BROSS, JEROEN R. SCHEEPE, CHRISTOPH SEIF, KLAUS-PETER m E M A " AND PETER ALKEN From the Neuro-Urological Laboratory, Department of Urology, Klinikum Mannheim, University of Heidelberg, Mannheim, Germany
ABSTRACT
Purpose: Cryotechnique for selective block of the urethral sphincter and simultaneous activation of the bladder was developed to achieve physiological micturition during sacral anterior root stimulation (SARS). Materials and Methods: In ten foxhounds SARS of S2 was carried out while extradurally both spinal nerves S2 were cooled down from positive 25C in a stepwise fashion until a sphincter block was observed. Subsequently, SARS of S2 was performed while the pudendal nerves were cooled down from + 15C. The effects of spinal and pudendal nerve cold block on the urethral sphincter and bladder during SARS and the recovery time were monitored by urodynamic investigation. Results: A complete cold block of the urethral sphincter during spinal nerve cooling was achieved in all cases. During pudendal nerve cooling, the sphincter was completely blocked in two, and incompletely blocked in four dogs. Cold block temperature of the spinal nerves averaged +11.7C and of the pudendal nerves +6.2C. During SARS and spinal nerve cooling, a n increase in intravesical pressure up to 13 cm. water was recognized, and recovery time was on average 6.6 minutes. Intravesical pressure remained unchanged during pudendal nerve cooling, with recovery time being less than 1 minute. The cold block was always reversible. Conclusions: Cryotechnique is a n excellent method for selective and reversible block of the urethral sphincter during SARS to avoid detrusor-sphincter-dyssynergia.The application of cryotechnique in functional electrical stimulation leads to an improvement of quality of life in para- or tetraplegic patients because of selective nerve stimulation with optimization of micturition, standing, walking and grasping and does so without the necessity of surgical dorsal root rhizotomy . KEYWORDS:selective neurostimulation, cryothermode, cold block, functional electrical stimulation
Anticholinergic therapy is often inadequate in patients with supraconal spinal cord injury who suffer from the loss of voluntary bladder control, detrusor hyperreflexia and sphincter spasm. Intermittent catheterization frequently becomes necessary because of inefficient bladder emptying. Sacral posterior rhizotomy combined with sacral anterior root stimulation (SARS)is still successfully employed for restoration of voiding function in these patients.'-5 A major drawback of conventional SARS is simultaneous, unphysiological contraction of bladder and urethral sphincter, as the stimulated nerve roots consist of both nonmyelinated fibers to the detrusor and myelinated fibers to the urethral sphincter. Clinical consequences are detrusor-sphincter-dyssynergiaand related complications such as increase of intravesical pressure, residual urine and recurrent urinary tract infections. Previous experimental studies were performed for selective activation of the bladder during simultaneous urethral sphincter block. Anodal block stimulation using tripolar cuff electrodes or a modified Brindley electrode enables this selectivity in animal In addition, we searched for further alternatives for selective neurostimulation. The neurophysiological blocking effect of cold on the nervous system is well known. Peripheral myelinated nerve fibers are more susceptible to failure at low temperatures than nonmyelinated fibers.'". ' ' We developed a new proce-
dure (cryotechnique) to block myelinated nerve fibers selectively while nonmyelinated fibers are still activated in a canine model. In foxhounds we evaluated the urodynamic effects of a selective cold block of myelinated nerve fibers in spinal and pudendal nerves on the urethral sphincter and bladder, respectively. Our aim is the development of a new technique to avoid detrusor-sphincter-dyssynergia during conventional SARS for urinary bladder control in para- or tetraplegic patients in the future. MATERIALS AND METHODS
In acute animal trials, a total of ten male foxhounds aged 7 to 18 months (b.w. 19.7 to 38.2 kg.) were premedicated with 1.5 to 2.0 ml. Combelen@intramuscularly (propionylpromazine, Bayer Leverkusen, Germany). Following intravenous injection with 200 to 250 mg. Trapanal@ (thiopental, Byk Gulden, Konstanz, Germany), the animals were intubated, anaesthetized with 1to 3% vol. Forenem (isofluorane, Abott, Wiesbaden, Germany) and supplied with oxygen (40% vol.). Electrocardiogram, heart frequency and body temperature were continously monitored. Blood gas analysis and measurement of Na+, K', and Ca++ were regularly performed (ABL 505, Radiometer, Copenhagen, Denmark). Each animal underwent lumbar laminectomy (L4 to L7) after placement of a suprapubic catheter and a transurethral rnicrotip catheter for urodynamic investigation (Urodynamic computer system Jupiter 8000, Wiest, Unterhaching, Germany). After opening of the dural space, sacral roots S2 and the accompanying spinal nerves, consisting of small nonmyelinated fibers to the bladder and large myelinated fibers to the
Accepted for publication September 2, 1998. * R e uests for reprints: Department of Urology, University of Bonn, Iigmund-Freud-Str. 25, D-53105 Bonn, Germany. Supported by a grant from the Federal Department of Education, Science, Research and Technology, Bonn, Germany (No. 01 KO 9504). 950
SELECTIVE NEUROSTIMULATION OF THE BLADDER IN CRYOTECHNIQUE urethral sphincter, were identified both visually and by test stimulation. The anterior sacral roots S2 were placed intradurally into a modified Brindley electrode. The two spinal nerves S2 were placed extradurally into a custom-made, patented cryothermode (Patent No. 19718995.4). During monitored stepwise cooling (1C) of the spinal nerves S2 from +25C down to the temperature that showed a sphincter block, simultaneous bilateral SARS of S2 was performed by a conventional technique (fig. 1,A). Stimulation patterns were applied using a Philips Function generator PM 5139 (Hamburg, Germany) with biphasic rectangular electrical stimuli, pulse width 200 psec., frequency 20 Hz and current strength 4 mA. Subsequently, in seven dogs, bilateral anatomical separation of the pudendal nerve in the ischiorectal fossa followed. The main nerve trunk or the urethral branch of the pudendal nerve of each side was placed separately into the cryothermode. Again, bilateral SARS of S2 (similar stimulation parameters) was performed fig. l, B . Bilaterally, the pudendal nerves were cooled down in 1C steps from +15C until a sphincter block was noted. Following successful cold block, the recovery time of the nerves (spinal nerves S2 or main trunk of the pudendal nerves or urethral branch of the pudendal nerves) was recorded by measuring the pressure increase of the urethral sphincter during neurostimulation. The effects of spinal nerve and pudendal nerve cold block on the urethral sphincter and urinary bladder were monitored by urodynamic investigation.
95 1
Statistical analysis was performed using Wilcoxon test. RESULTS
In ten foxhounds, bilateral intradural SARS of S2, in combination with simultaneous extradural cooling of the accompanying spinal nerves, was performed. We chose the nerves S2 to demonstrate the success of cryotechnique, as in our canine model these anterior roots consist of both small nonmyelinated fibers to the bladder and large myelinated fibers to the urethral sphincter. An overview of the data in each dog is given in table 1. A complete cold block of the urethral sphincter was achieved in all cases (fig. 2). The difference of the mean urethral pressure before and during cold block was highly significant (p <0,0005). The cold block temperature (fig. 4) ranged between +7C and + 15C (mean + 11.7C). A n increase in intravesical pressure up to 13 cm. water (mean 5.2 cm. water) was recognized during complete urethral sphincter block and simultaneous neurostimulation using constant stimulation parameters. In two cases, we found no increase in bladder pressure while the urethral sphincter was blocked (table 1). In one of these dogs, we performed a simultaneous bilateral neurostimulation of S2 and S3 while the urethral sphincter was blocked. The anterior roots S3 chiefly consist of nonmyelinated fibers to the bladder and sometimes myelinated fibers to the urethral sphincter. With this technique, we observed an increase in bladder pressure of a t least 15 cm. water.
FIG. 1. A , intraoperative placement of modified Brindley electrode and cryothermode (spinal nerves). B , intraoperative placement of modified Brindley electrode and cryothermode (pudendal nerves).
952
SELECTIVE NEUROSTIMULATION OF THE BLADDER IN CRYOTECHNIQUE TABLE 1. Data from ten dogs with SARS of S2 and cooling of spinal nerves S2
Block temp.
Recovery time
Initial urethral pressure
Urethral block pressure
Initial detrusor pressure
12c 23 min. 49 cm H,O 0 cm H,O 14C 35 min. 61 cm H,O 0 cm H 2 0 13C 1 min. 59 em H,O 0 em H,O 1OC 1 min. 22 em H 2 0 0 cm H,O 13C 1 min. 27 cm H,O 0 cm H 2 0 15C 1 min. 10 cm H,O 0 cm H,O 12c 1 min. 110 cm H,O 0 cm H,O 7c 1 min. 30 cm H,O 0 cm H 2 0 14C 1 min. 74 em H - 0 0 cm H - 0 7c 1 min. 106 cm H ~ O o cm H;O * SARS of S2 and S3 led to an increase of bladder pressure of at least 15 cm water during sphincter block.
FIG.2. Conventional sacral anterior root stimulation of S2 with initial s hincter pressure and sphincter pressure during maximum bilaterarcooling of spinal nerves S2.
66 cm H,O 55 cm H,O 16 cm H,O 67 cm H20 45 cm H,O 59 cm H,O 46 cm H,O 54 cm H,O 44 cm H,O 71 cm H i 0
Detrusor pressure during block
6 cm H,O 10 cm H,O 3 em H,O 9 cm H,O 2 cm H,O 13 cm H,O 0 cm H,O *O cm H,O 2 cm H,O 7 cm H ~ O
FIG. 3. Conventional sacral anterior root stimulation of S2 with initial s hincter pressure and sphincter pressure during maximum bilaterarcooling of pudendal nerves.
Cold block of the urethral sphincter was completely reversThe recovery time of the spinal nerves S2 after cold block ible in both series. ranged between 1and 35 minutes (mean 6.6 minutes.). SARS of S2 and simultaneous stepwise cooling of the puDISCUSSION dendal nerves were carried out in seven of these dogs. An overview of the data in each dog is given in table 2. A Previous experimental studies have already described a complete cold block of the sphincter was observed in two technique for selective activation of the urinary bladder and animals. An incomplete sphincter block with urethral sphinc- selective block of the urethral sphincter to achieve a physioter pressure ranging from 3 to 17 cm. water (mean 10.8 cm. logical voiding pattern6-’. ‘* water) was registered in four animals. It was not possible to In our animal model, we made the first observations with block the pudendal nerves in one foxhound (fig. 3). In all a newly developed cryotechnique for selective cold block cases, the difference in mean urethral pressure before and of myelinated nerve fibers to the urethral sphincter while during cold block of the pudendal nerves was highly signifi- nonmyelinated fibers to the detrusor are activated during cant (p <0,005). neurostimulation, which has never been shown before. The cold block temperature (fig. 4) averaged +6.2C (+3C to Local cooling alters membrane permeabilities for specific + 12C). lntravesical pressure remained unchanged during ions, such as Na’, K’ and C a + + .Physiological effects are investigation in all cases of this series; the difference be- diverse because they are composed of cellular effects that tween the mean detrusor pressure before cold block (mean can differ for various parts of the central nervous system 51.3 cm. water) and during cold block (mean 51.2 cm. water) and for various types of neurons.” At low temperatures was not significant. The recovery time of the pudendal nerve (<20C) the resting potential of nerve fibers is practically averaged less than 1 minute (table 2). ~ 0 n s t a n t . The l ~ action potential increased in amplitude as
TABLE2. Data from seven dogs with SARS of S2 and cooling of pudendal nerves Block temp.
3c 6c 1OC no block 2c 12c 4c
Recovery time 1 min. 0,3 min. 0.3 min. 1 min. 0.3 min. 0,7 min.
Initial urethral pressure 45 em H,O 35 cm HzO 40 cm HzO 43 em H,O 39 cm H,O 40 cm H,O 33 cm H,O
Urethral block pressure
Initial detrusor pressure
Detrusor pressure during block
13 cm H,O 3 em H 2 0 0 cm H,O 40 em H,O 0 cm H,O 10 cm H,O 17 cm H,O
39 cm H,O 27 cm H 2 0 56 cm H,O
40 cm H,O 18 cm H,O
70 em H,O 61 cm H,O 55 cm H,O
86 cm H,O 75 cm H,O 40 cm H,O
48 cm H,O
953
SELECTIVE NEUROSTIMULATION OF THE BLADDER IN CRYOTECHNIQUE
the success rate of sufficient sphincter block was 85.78 (fig. 3). A possible explanation is the difficult positioning of the oversized cryothermode prototype in the narrow ischiorectal fossa resulting in ineffective application of cold to the pudendal nerves. To improve the results of a complete bilateral cold block of the pudendal nerves, technical equipment should be optimally adapted to the anatomical location of the pudendal nerve in the ischiorectal fossa (size of cryothermode, optimization of nerve cuff design, and so forth). In all cases, the bladder pressure remained unchanged under neurostimulation during cold block of pudendal nerves. The bladder was still activated during urethral sphincter block in 8 0 8 of all dogs during spinal nerve cooling of S2. The increase of bladder pressure during SARS of S2 averaged 5.2 cm. water. Further investigations will be carried out to optimize the combination of spinal nerve cold block and SARS with multiple channel stimulation of different anterior roots, for example combination of S2 and S3 and varying stimulation parameters, for example frequency, curFIG. 4. Temperature (C) during maximum achieved cold block of rent strength, and so forth, to increase the bladder pressure. spinal and pudendal nerves. In one single trial carried out by us, we observed that a combination of SARS of S2 and S3 significantly increased the bladder pressure during complete sphincter block because the temperature d r 0 ~ p e d . ll~ 4 .The velocity at which imthe anterior roots S3 chiefly consist of nonmyelinated fibers pulses were conducted in individual axons through the to the detrusor (table 1). cooled length of nerve slowed progressively as the temperThough the anesthetic model might influence the spontaature declined. Peripheral myelinated A fibers block at neous activation of the bladder, this fact didn't influence our mean +7.3C (range between +10.4C and +2.6C). The av- results. During anesthesia, we performed direct electrical erage of blocked nonmyelinated C fibers is found at nerve stimulation with and without the application of cold to +2.7C.'O." The explanation for the reduced effect of tem- compare the influence on urodynamic results under same perature on nonmyelinated conduction is not apparent, but conditions. the effect of the reduced rate of slowing is clear: critical Cryotechnique has an experimental status now, but if clinminimum conduction velocities were reached at higher ical evaluation of the cryotechnique is successful this method temperatures in myelinated axons than in nonmyelinated may enable a wide field of additional applications in humans. ones." Nonmyelinated C fibers have a higher safety factor Nowadays, sacral posterior rhizotomy is the "golden stanfor transmission than myelinated A fibers, perhaps due t o dard" for the restoration of bladder volume and reattainment longer durations of their action potentials." Our own results during cold block of pudendal nerves (con- of continence in para- or tetraplegic patient^.^." For example sisting of sensory and motor fibers with myelinated compo- deafferentation of S2 leads to the loss of reflex erection and nents to the external urethral sphincter) with a mean cold reflex ejaculation in males and the loss of vaginal lubrication block temperature of +6.2C correlate with these findings. in females. Temporary, reversible deafferentation with cold However, mean blocking temperature for spinal nerves was block of both posterior roots S2 could solve these problems. In addition to neurostimulation of the bladder, cryotech+11.7C and thus +5.5C higher than the blocking temperature for pudendal nerves. This thermal gradient is probably nique may be indicated in the development of a neural proscaused by the close location of the thermode to the spinal cord thesis of the external urethral sphincter. Direct electrostimuas part of the central nervous system during spinal nerve lation of the urethral branch of the pudendal nerve enables cooling. This supposition is based on observations indicating selective urethral sphincter contractions. that local brain cooling causes block of central synapses near Pudendal nerve cold block proximal to the stimulation +20C, while fiber tracts conduct to near +lOC." The main electrode may block afferent fibers of the pudendal nerve and advantage of the cooling method is the ability to produce thus pain sensations during stimulation. Furthermore, this repeated, brief, local, reversible dysfunctions, without the technique widens the indication criteria of neurostimulation compensatory neuronal reorganization that occurs after per- for other neurogenic lesions that lead to neurogenic bladder manent lesions." No information at all was found in the dysfunction, for example multiple sclerosis and so forth. literature on the exact duration of recovery time after local This procedure could replace surgical rhizotomy of the nerve cooling. Our investigations showed a period of recovery pudendal nerve in cases of extreme detrusor-sphincter dysaveraging 6.6 minutes to restoration of function, depending synergia during extradural SARS in the Tanagho-Schmidt on the position of the thermode. Recovery time duration of technique.'" In patients for whom spinal nerve cooling is not spinal nerve cooling was longer than that of pudendal nerve feasible for any reason, pudendal nerve cooling could be an cooling (table 1,table 2). Again, this is probably caused by the alternate technique to accomplish the goal of improved bladclose location of the thermode to the spinal cord and the der emptying with SARS. maximum cooling temperature. As an exception, in the two After finishing basic physiological research, cryotechnique cases of spinal nerve cooling showing recovery times of 23 minutes and 35 minutes (table l),the spinal nerves were may become more significant in functional electrical stimucooled down to OC. Maybe because this temperature was lation during the application of selective stimulation systems close to the freezing point, the recovery time was longer. that enable standing, walking and grasping. This new kind of Normal function returns upon rewarming, if freezing is neurostimulation is aimed at selective activation of muscle avoided." There is no systematic knowledge of the mecha- groups with consecutive reduction of spasticity. Furthermore, the application of cryotechnique for selective nism at present. During spinal nerve cooling, the success rate of sphincter block of afferent nerve fibers is conceivable in patients with block was 100% (fig. 2). During cooling of pudendal nerves, chronic pain.
''
954
SELECTrVE NEUROSTIMULATION OF THE BLADDER IN CRYOTECHNIQUE CONCLUSIONS
Cryotechnique is an excellent method for selective block of nerve fibers. D u r i n g neurostimulation of the bladder a complete a n d reversible block of the urethral sphincter c a n be achieved while bladder activity is preserved. If these prelimi n a r y results can be reproduced in chronic trials and also d u r i n g intraoperative patient evaluation, t h i s technique could be introduced i n t o clinical practice. The application of cryotechnique in the field of functional electrical stimulation leads to an improvement of quality of life in para- or tetraplegic patients because of a selective neurostimulation and a reduction of stimulation-related complications.
REFERENCES
1. Brindley, G. S., Polkey, C. E. and Rushton, D. N.: Sacral anterior root stimulator for bladder control in paraplegia. Paraplegia, 2 0 365, 1982. 2. Brindley, G. S., Polkey, C. E., Rushton, D. N. and Cardozo, D. N.: Sacral anterior root stimulators for bladder control in paraplegia: the first 50 cases. J. Neurol. Neurosurg. Psychiatr., 49: 1104, 1986. 3. Brindley, G. S. and Rushton, D. N.: Long-term follow-up of patients with sacral anterior root stimulator implants. Paraplegia, 2 8 469, 1990. 4. Sauerwein, D.: Die operative Behandlung der spastischen Blasenlahmung bei Querschnittlahmung: Sakrale Deafferentation (SDAF)mit der Implantation eines sakralen Vorderwurzelstimulators (SARS).Urologe A, 2 9 196, 1990. 5. Schmidt, R. A. and Tanagho, E. A.: Neuromicturition. Extradural sacral nerve-root stimulation: guidelines for patient selection and implant techniques. World J . Urol., 9 114, 1991. 6. Koldewijn, E. L., Rijkhoff, N. J. M., Van Kerrebroeck, P. E. V., Debruyne, F. M. J . and Wijkstra, H.: Selective stimulation of
sacral nerves for bladder control in an animal model. J. Urol., 149: 357A.1993. 7. Wipfler, G., Griinewald, V., Bhadra, N., Creasey, G. H. and Mortimer J. T.: Selektive Aktiviemng der Blase mittels Sakralwurzelstimulation unter Verwendung quasitrapezoidaler elektrischer Impulse beim Hund. Akt. Urol., 2 6 13, 1995. 8. Wipfler, G., Scheepe, J . R., Seif, C., Gropp, A., Berle, B., Zendler, S., Jiinemann, K-P. and Alken, P.: Selektive sakrale Vorderwurzelstimulation der Blase mittels Anodenblocktechnik unter Verwendung einer modifizierten Brindley-Elektrode beim Hund. Akt. Urol., 28: 164, 1997. 9. 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. 10. Franz, D. N. and Iggo, A.: Conduction failure in myelinated and non-myelinated axons at low temperatures. J. Physiol. (Lond), 199.319, 1968. 11. Brooks, V. B.: Study of brain function by local, reversible cooling. Rev. Physiol. Biochem. Pharmacol., 95: 1, 1983. 12. Rijkhoff, N. J. M., Koldewijn, E. L., Van Kerrebroek, P. E. V., Debruyne, F. M. J . and Wijkstra, H.: Sacral root stimulation in the dog: reduction of urethral resistance. Proc. 15thAnnu: Int. Conf. IEEE-EMBS: 1257, 1993. 13. Schoepfle, G . M., Erlanger, J.: The action of temperature on the excitability, spike height and configuration, and the refractory period observed in the responses of single medullated nerve fibers. Am. J. Physiol., 134: 694, 1942. 14. Hodgkin, A. L. and Katz, B.: The effect of temperature on the electrical activity of the giant axon of the squid. J. Physiol. (Lond.), 109: 240, 1949. 15. Schumacher, S., Scheepe, J. R., Bross, S., Weiss, J., Junemann, K. P. and Alken, P.: The urodynamic effects of direct electrostimulation on the urethral branch of the pudendal nerve. J. Urol. (Suppl. 1, 157: 80, 1997. 16. Schmidt, R. A.: Applications of neurostimulation in urology. Neurourol. Urodyn., 7: 585, 1988.
Vol. 161,950-954,March 1999 Printed in U.S.A.
JOURNAL OF UROLOGY
Copyright @ 1999 by AMERICm
UROLoClCAL kssocLsTlON,
INC.
EXTRADURAL COLD BLOCK FOR SELECTIVE NEUROSTIMULATION OF THE BLADDER: DEVELOPMENT OF A NEW TECHNIQUE STEFAN SCHUMACHER,* STEPHAN BROSS, JEROEN R. SCHEEPE, CHRISTOPH SEIF, KLAUS-PETER m E M A " AND PETER ALKEN From the Neuro-Urological Laboratory, Department of Urology, Klinikum Mannheim, University of Heidelberg, Mannheim, Germany
ABSTRACT
Purpose: Cryotechnique for selective block of the urethral sphincter and simultaneous activation of the bladder was developed to achieve physiological micturition during sacral anterior root stimulation (SARS). Materials and Methods: In ten foxhounds SARS of S2 was carried out while extradurally both spinal nerves S2 were cooled down from positive 25C in a stepwise fashion until a sphincter block was observed. Subsequently, SARS of S2 was performed while the pudendal nerves were cooled down from + 15C. The effects of spinal and pudendal nerve cold block on the urethral sphincter and bladder during SARS and the recovery time were monitored by urodynamic investigation. Results: A complete cold block of the urethral sphincter during spinal nerve cooling was achieved in all cases. During pudendal nerve cooling, the sphincter was completely blocked in two, and incompletely blocked in four dogs. Cold block temperature of the spinal nerves averaged +11.7C and of the pudendal nerves +6.2C. During SARS and spinal nerve cooling, a n increase in intravesical pressure up to 13 cm. water was recognized, and recovery time was on average 6.6 minutes. Intravesical pressure remained unchanged during pudendal nerve cooling, with recovery time being less than 1 minute. The cold block was always reversible. Conclusions: Cryotechnique is a n excellent method for selective and reversible block of the urethral sphincter during SARS to avoid detrusor-sphincter-dyssynergia.The application of cryotechnique in functional electrical stimulation leads to an improvement of quality of life in para- or tetraplegic patients because of selective nerve stimulation with optimization of micturition, standing, walking and grasping and does so without the necessity of surgical dorsal root rhizotomy . KEYWORDS:selective neurostimulation, cryothermode, cold block, functional electrical stimulation
Anticholinergic therapy is often inadequate in patients with supraconal spinal cord injury who suffer from the loss of voluntary bladder control, detrusor hyperreflexia and sphincter spasm. Intermittent catheterization frequently becomes necessary because of inefficient bladder emptying. Sacral posterior rhizotomy combined with sacral anterior root stimulation (SARS)is still successfully employed for restoration of voiding function in these patients.'-5 A major drawback of conventional SARS is simultaneous, unphysiological contraction of bladder and urethral sphincter, as the stimulated nerve roots consist of both nonmyelinated fibers to the detrusor and myelinated fibers to the urethral sphincter. Clinical consequences are detrusor-sphincter-dyssynergiaand related complications such as increase of intravesical pressure, residual urine and recurrent urinary tract infections. Previous experimental studies were performed for selective activation of the bladder during simultaneous urethral sphincter block. Anodal block stimulation using tripolar cuff electrodes or a modified Brindley electrode enables this selectivity in animal In addition, we searched for further alternatives for selective neurostimulation. The neurophysiological blocking effect of cold on the nervous system is well known. Peripheral myelinated nerve fibers are more susceptible to failure at low temperatures than nonmyelinated fibers.'". ' ' We developed a new proce-
dure (cryotechnique) to block myelinated nerve fibers selectively while nonmyelinated fibers are still activated in a canine model. In foxhounds we evaluated the urodynamic effects of a selective cold block of myelinated nerve fibers in spinal and pudendal nerves on the urethral sphincter and bladder, respectively. Our aim is the development of a new technique to avoid detrusor-sphincter-dyssynergia during conventional SARS for urinary bladder control in para- or tetraplegic patients in the future. MATERIALS AND METHODS
In acute animal trials, a total of ten male foxhounds aged 7 to 18 months (b.w. 19.7 to 38.2 kg.) were premedicated with 1.5 to 2.0 ml. Combelen@intramuscularly (propionylpromazine, Bayer Leverkusen, Germany). Following intravenous injection with 200 to 250 mg. Trapanal@ (thiopental, Byk Gulden, Konstanz, Germany), the animals were intubated, anaesthetized with 1to 3% vol. Forenem (isofluorane, Abott, Wiesbaden, Germany) and supplied with oxygen (40% vol.). Electrocardiogram, heart frequency and body temperature were continously monitored. Blood gas analysis and measurement of Na+, K', and Ca++ were regularly performed (ABL 505, Radiometer, Copenhagen, Denmark). Each animal underwent lumbar laminectomy (L4 to L7) after placement of a suprapubic catheter and a transurethral rnicrotip catheter for urodynamic investigation (Urodynamic computer system Jupiter 8000, Wiest, Unterhaching, Germany). After opening of the dural space, sacral roots S2 and the accompanying spinal nerves, consisting of small nonmyelinated fibers to the bladder and large myelinated fibers to the
Accepted for publication September 2, 1998. * R e uests for reprints: Department of Urology, University of Bonn, Iigmund-Freud-Str. 25, D-53105 Bonn, Germany. Supported by a grant from the Federal Department of Education, Science, Research and Technology, Bonn, Germany (No. 01 KO 9504). 950
SELECTIVE NEUROSTIMULATION OF THE BLADDER IN CRYOTECHNIQUE urethral sphincter, were identified both visually and by test stimulation. The anterior sacral roots S2 were placed intradurally into a modified Brindley electrode. The two spinal nerves S2 were placed extradurally into a custom-made, patented cryothermode (Patent No. 19718995.4). During monitored stepwise cooling (1C) of the spinal nerves S2 from +25C down to the temperature that showed a sphincter block, simultaneous bilateral SARS of S2 was performed by a conventional technique (fig. 1,A). Stimulation patterns were applied using a Philips Function generator PM 5139 (Hamburg, Germany) with biphasic rectangular electrical stimuli, pulse width 200 psec., frequency 20 Hz and current strength 4 mA. Subsequently, in seven dogs, bilateral anatomical separation of the pudendal nerve in the ischiorectal fossa followed. The main nerve trunk or the urethral branch of the pudendal nerve of each side was placed separately into the cryothermode. Again, bilateral SARS of S2 (similar stimulation parameters) was performed fig. l, B . Bilaterally, the pudendal nerves were cooled down in 1C steps from +15C until a sphincter block was noted. Following successful cold block, the recovery time of the nerves (spinal nerves S2 or main trunk of the pudendal nerves or urethral branch of the pudendal nerves) was recorded by measuring the pressure increase of the urethral sphincter during neurostimulation. The effects of spinal nerve and pudendal nerve cold block on the urethral sphincter and urinary bladder were monitored by urodynamic investigation.
95 1
Statistical analysis was performed using Wilcoxon test. RESULTS
In ten foxhounds, bilateral intradural SARS of S2, in combination with simultaneous extradural cooling of the accompanying spinal nerves, was performed. We chose the nerves S2 to demonstrate the success of cryotechnique, as in our canine model these anterior roots consist of both small nonmyelinated fibers to the bladder and large myelinated fibers to the urethral sphincter. An overview of the data in each dog is given in table 1. A complete cold block of the urethral sphincter was achieved in all cases (fig. 2). The difference of the mean urethral pressure before and during cold block was highly significant (p <0,0005). The cold block temperature (fig. 4) ranged between +7C and + 15C (mean + 11.7C). A n increase in intravesical pressure up to 13 cm. water (mean 5.2 cm. water) was recognized during complete urethral sphincter block and simultaneous neurostimulation using constant stimulation parameters. In two cases, we found no increase in bladder pressure while the urethral sphincter was blocked (table 1). In one of these dogs, we performed a simultaneous bilateral neurostimulation of S2 and S3 while the urethral sphincter was blocked. The anterior roots S3 chiefly consist of nonmyelinated fibers to the bladder and sometimes myelinated fibers to the urethral sphincter. With this technique, we observed an increase in bladder pressure of a t least 15 cm. water.
FIG. 1. A , intraoperative placement of modified Brindley electrode and cryothermode (spinal nerves). B , intraoperative placement of modified Brindley electrode and cryothermode (pudendal nerves).
952
SELECTIVE NEUROSTIMULATION OF THE BLADDER IN CRYOTECHNIQUE TABLE 1. Data from ten dogs with SARS of S2 and cooling of spinal nerves S2
Block temp.
Recovery time
Initial urethral pressure
Urethral block pressure
Initial detrusor pressure
12c 23 min. 49 cm H,O 0 cm H,O 14C 35 min. 61 cm H,O 0 cm H 2 0 13C 1 min. 59 em H,O 0 em H,O 1OC 1 min. 22 em H 2 0 0 cm H,O 13C 1 min. 27 cm H,O 0 cm H 2 0 15C 1 min. 10 cm H,O 0 cm H,O 12c 1 min. 110 cm H,O 0 cm H,O 7c 1 min. 30 cm H,O 0 cm H 2 0 14C 1 min. 74 em H - 0 0 cm H - 0 7c 1 min. 106 cm H ~ O o cm H;O * SARS of S2 and S3 led to an increase of bladder pressure of at least 15 cm water during sphincter block.
FIG.2. Conventional sacral anterior root stimulation of S2 with initial s hincter pressure and sphincter pressure during maximum bilaterarcooling of spinal nerves S2.
66 cm H,O 55 cm H,O 16 cm H,O 67 cm H20 45 cm H,O 59 cm H,O 46 cm H,O 54 cm H,O 44 cm H,O 71 cm H i 0
Detrusor pressure during block
6 cm H,O 10 cm H,O 3 em H,O 9 cm H,O 2 cm H,O 13 cm H,O 0 cm H,O *O cm H,O 2 cm H,O 7 cm H ~ O
FIG. 3. Conventional sacral anterior root stimulation of S2 with initial s hincter pressure and sphincter pressure during maximum bilaterarcooling of pudendal nerves.
Cold block of the urethral sphincter was completely reversThe recovery time of the spinal nerves S2 after cold block ible in both series. ranged between 1and 35 minutes (mean 6.6 minutes.). SARS of S2 and simultaneous stepwise cooling of the puDISCUSSION dendal nerves were carried out in seven of these dogs. An overview of the data in each dog is given in table 2. A Previous experimental studies have already described a complete cold block of the sphincter was observed in two technique for selective activation of the urinary bladder and animals. An incomplete sphincter block with urethral sphinc- selective block of the urethral sphincter to achieve a physioter pressure ranging from 3 to 17 cm. water (mean 10.8 cm. logical voiding pattern6-’. ‘* water) was registered in four animals. It was not possible to In our animal model, we made the first observations with block the pudendal nerves in one foxhound (fig. 3). In all a newly developed cryotechnique for selective cold block cases, the difference in mean urethral pressure before and of myelinated nerve fibers to the urethral sphincter while during cold block of the pudendal nerves was highly signifi- nonmyelinated fibers to the detrusor are activated during cant (p <0,005). neurostimulation, which has never been shown before. The cold block temperature (fig. 4) averaged +6.2C (+3C to Local cooling alters membrane permeabilities for specific + 12C). lntravesical pressure remained unchanged during ions, such as Na’, K’ and C a + + .Physiological effects are investigation in all cases of this series; the difference be- diverse because they are composed of cellular effects that tween the mean detrusor pressure before cold block (mean can differ for various parts of the central nervous system 51.3 cm. water) and during cold block (mean 51.2 cm. water) and for various types of neurons.” At low temperatures was not significant. The recovery time of the pudendal nerve (<20C) the resting potential of nerve fibers is practically averaged less than 1 minute (table 2). ~ 0 n s t a n t . The l ~ action potential increased in amplitude as
TABLE2. Data from seven dogs with SARS of S2 and cooling of pudendal nerves Block temp.
3c 6c 1OC no block 2c 12c 4c
Recovery time 1 min. 0,3 min. 0.3 min. 1 min. 0.3 min. 0,7 min.
Initial urethral pressure 45 em H,O 35 cm HzO 40 cm HzO 43 em H,O 39 cm H,O 40 cm H,O 33 cm H,O
Urethral block pressure
Initial detrusor pressure
Detrusor pressure during block
13 cm H,O 3 em H 2 0 0 cm H,O 40 em H,O 0 cm H,O 10 cm H,O 17 cm H,O
39 cm H,O 27 cm H 2 0 56 cm H,O
40 cm H,O 18 cm H,O
70 em H,O 61 cm H,O 55 cm H,O
86 cm H,O 75 cm H,O 40 cm H,O
48 cm H,O
953
SELECTIVE NEUROSTIMULATION OF THE BLADDER IN CRYOTECHNIQUE
the success rate of sufficient sphincter block was 85.78 (fig. 3). A possible explanation is the difficult positioning of the oversized cryothermode prototype in the narrow ischiorectal fossa resulting in ineffective application of cold to the pudendal nerves. To improve the results of a complete bilateral cold block of the pudendal nerves, technical equipment should be optimally adapted to the anatomical location of the pudendal nerve in the ischiorectal fossa (size of cryothermode, optimization of nerve cuff design, and so forth). In all cases, the bladder pressure remained unchanged under neurostimulation during cold block of pudendal nerves. The bladder was still activated during urethral sphincter block in 8 0 8 of all dogs during spinal nerve cooling of S2. The increase of bladder pressure during SARS of S2 averaged 5.2 cm. water. Further investigations will be carried out to optimize the combination of spinal nerve cold block and SARS with multiple channel stimulation of different anterior roots, for example combination of S2 and S3 and varying stimulation parameters, for example frequency, curFIG. 4. Temperature (C) during maximum achieved cold block of rent strength, and so forth, to increase the bladder pressure. spinal and pudendal nerves. In one single trial carried out by us, we observed that a combination of SARS of S2 and S3 significantly increased the bladder pressure during complete sphincter block because the temperature d r 0 ~ p e d . ll~ 4 .The velocity at which imthe anterior roots S3 chiefly consist of nonmyelinated fibers pulses were conducted in individual axons through the to the detrusor (table 1). cooled length of nerve slowed progressively as the temperThough the anesthetic model might influence the spontaature declined. Peripheral myelinated A fibers block at neous activation of the bladder, this fact didn't influence our mean +7.3C (range between +10.4C and +2.6C). The av- results. During anesthesia, we performed direct electrical erage of blocked nonmyelinated C fibers is found at nerve stimulation with and without the application of cold to +2.7C.'O." The explanation for the reduced effect of tem- compare the influence on urodynamic results under same perature on nonmyelinated conduction is not apparent, but conditions. the effect of the reduced rate of slowing is clear: critical Cryotechnique has an experimental status now, but if clinminimum conduction velocities were reached at higher ical evaluation of the cryotechnique is successful this method temperatures in myelinated axons than in nonmyelinated may enable a wide field of additional applications in humans. ones." Nonmyelinated C fibers have a higher safety factor Nowadays, sacral posterior rhizotomy is the "golden stanfor transmission than myelinated A fibers, perhaps due t o dard" for the restoration of bladder volume and reattainment longer durations of their action potentials." Our own results during cold block of pudendal nerves (con- of continence in para- or tetraplegic patient^.^." For example sisting of sensory and motor fibers with myelinated compo- deafferentation of S2 leads to the loss of reflex erection and nents to the external urethral sphincter) with a mean cold reflex ejaculation in males and the loss of vaginal lubrication block temperature of +6.2C correlate with these findings. in females. Temporary, reversible deafferentation with cold However, mean blocking temperature for spinal nerves was block of both posterior roots S2 could solve these problems. In addition to neurostimulation of the bladder, cryotech+11.7C and thus +5.5C higher than the blocking temperature for pudendal nerves. This thermal gradient is probably nique may be indicated in the development of a neural proscaused by the close location of the thermode to the spinal cord thesis of the external urethral sphincter. Direct electrostimuas part of the central nervous system during spinal nerve lation of the urethral branch of the pudendal nerve enables cooling. This supposition is based on observations indicating selective urethral sphincter contractions. that local brain cooling causes block of central synapses near Pudendal nerve cold block proximal to the stimulation +20C, while fiber tracts conduct to near +lOC." The main electrode may block afferent fibers of the pudendal nerve and advantage of the cooling method is the ability to produce thus pain sensations during stimulation. Furthermore, this repeated, brief, local, reversible dysfunctions, without the technique widens the indication criteria of neurostimulation compensatory neuronal reorganization that occurs after per- for other neurogenic lesions that lead to neurogenic bladder manent lesions." No information at all was found in the dysfunction, for example multiple sclerosis and so forth. literature on the exact duration of recovery time after local This procedure could replace surgical rhizotomy of the nerve cooling. Our investigations showed a period of recovery pudendal nerve in cases of extreme detrusor-sphincter dysaveraging 6.6 minutes to restoration of function, depending synergia during extradural SARS in the Tanagho-Schmidt on the position of the thermode. Recovery time duration of technique.'" In patients for whom spinal nerve cooling is not spinal nerve cooling was longer than that of pudendal nerve feasible for any reason, pudendal nerve cooling could be an cooling (table 1,table 2). Again, this is probably caused by the alternate technique to accomplish the goal of improved bladclose location of the thermode to the spinal cord and the der emptying with SARS. maximum cooling temperature. As an exception, in the two After finishing basic physiological research, cryotechnique cases of spinal nerve cooling showing recovery times of 23 minutes and 35 minutes (table l),the spinal nerves were may become more significant in functional electrical stimucooled down to OC. Maybe because this temperature was lation during the application of selective stimulation systems close to the freezing point, the recovery time was longer. that enable standing, walking and grasping. This new kind of Normal function returns upon rewarming, if freezing is neurostimulation is aimed at selective activation of muscle avoided." There is no systematic knowledge of the mecha- groups with consecutive reduction of spasticity. Furthermore, the application of cryotechnique for selective nism at present. During spinal nerve cooling, the success rate of sphincter block of afferent nerve fibers is conceivable in patients with block was 100% (fig. 2). During cooling of pudendal nerves, chronic pain.
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954
SELECTrVE NEUROSTIMULATION OF THE BLADDER IN CRYOTECHNIQUE CONCLUSIONS
Cryotechnique is an excellent method for selective block of nerve fibers. D u r i n g neurostimulation of the bladder a complete a n d reversible block of the urethral sphincter c a n be achieved while bladder activity is preserved. If these prelimi n a r y results can be reproduced in chronic trials and also d u r i n g intraoperative patient evaluation, t h i s technique could be introduced i n t o clinical practice. The application of cryotechnique in the field of functional electrical stimulation leads to an improvement of quality of life in para- or tetraplegic patients because of a selective neurostimulation and a reduction of stimulation-related complications.
REFERENCES
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