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Urodynamics in Children. Part I. Methodology
0022-5347 /81/1254-0530$02.00/0 Vol. 125, April
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright© 1981 by The Williams & Wilkins Co.
Urological Neurology and Urodynamics URODYNAMICS IN CHILDREN. PART I. METHODOLOGY MONEER K. HANNA,* WILLIAM DI SCIPIO, KYOUNG K. SUH, STANLEY J. KOGAN, SELWYN B. LEVITT AND KENNETH DONNER From the Division of Pediatric Urology, Children's Hospital of New Jersey, Newark, New Jersey, and Division of Pediatric Urology, and Departments of Anesthesia and Psychiatry, Hospital of the Albert Einstein College of Medicine and Montefiore Hospital and Medical Center, Bronx, New York
ABSTRACT
We evaluated 237 children for various urologic disorders in the urodynamic laboratory. A total of 334 studies was done, using a 6-channel recordert combined with a portable fluoroscopic unit. Simultaneous recordings of intravesical pressure, intra-abdominal pressure, urine flow rate, external urethral electromyography and cystourethrography were obtained during bladder filling and voiding. These objective tests have provided us with an insight into the nature of a variety of voiding dysfunctions in children. Details of the methods used for urodynamic testing in these children are outlined and compared to other methods that have been proposed. Dynamic studies of the lower urinary tract in adults have been discussed extensively. The application and adaptation of urodynamic testing of children have gained acceptance recently as a clinical rather than a research modality. 1- 4 It has become clear that measurements of isolated events during bladder filling or voiding result in erroneous interpretations. Dynamic studies provide the opportunity to study micturition continuously during all of its phases, allowing for more accurate identification of pathophysiologic events. Herein we report on the simultaneous recordings of the various functional parameters of the lower urinary tract in children. The methodology is described in detail. It has been designed especially for children and avoids all painful stimuli on the day of the urodynamic test. Anxiety and discomfort produce artifacts that render the study results uninterpretable. MATERIALS AND METHODS
Selection of patients. Early in our experience urociynamic studies were reserved for a select group of children who were either frequently infected and/or incontinent, despite continuous antibacterial therapy, empiric pharmacologic manipulation and urethral dilation. The excellent results of therapy directed by the urodynamic testing in this recalcitrant group of children who had failed to respond to conventional therapy prompted us to become more liberal with our indications for the tests (table 1). Currently, all children with persistent voiding symptoms or those who become infected while on continuous antibacterial therapy are studied. Children with clinical neuropathy, as well as those who are candidates for urinary undiversion, are investigated routinely. We do not study nocturnal enuretics but we obtain measurements of the urine flow rate in an outpatient setting. Initial evaluation. Following completion of the standard urologic studies, including history, physical examination, urinalysis and culture, excretory urography with upright anteroposterior and oblique films of the bladder base and a voiding cystourethrogram, an outpatient flow rate is obtained. The Accepted for publication July 14, 1980. * Address for reprints: Children's Hospital of New Jersey, 15 South Ninth St., Newark, New Jersey 07107. t Rack version of DISA urological investigation system, DISA Electronics, Franklin Lakes, New Jersey 07 417. 530
child and parents are then interviewed simultaneously with a pediatric urologist and a child psychologist. The urodynamic procedure, its implications and the information being sought from the tests are explained carefully to the parents and child. Psychological assessment of the child and family is conducted to identify any source of maladaptive anxiety, as well as to help establish appropriate coping strategies. A videotape of the urodynamic procedure, showing an age-appropriate child, is reviewed with the family and is followed by a discussion with the psychologist. Neurological evaluation is done, the x-rays are reviewed and a plan is made for urodynamic testing. All medications that may affect bladder and urethral functions are discontinued 1 week before admission to the urodynamic unit. The day in the hospital also allows documentation of the child's voiding habits and pattern. Urodynamic testing. Pre-anesthetic medications are deliberately not given. The child urinates into the flowmeter and is then catheterized. The residual urine is recorded. Conventional gas cystometry, provocative cystometry and urethral pressure profilometry are done in older and more cooperative children before the induction of anesthesia. Thereafter, cystourethroscopy is performed with the child under general anesthesia. Under direct cystoscopic control the full bladder is palpated and a trocar is introduced into the bladder. When there is fluid return an SF cystocathetert is advanced through the sheath under direct vision panendoscopic control. We then insert 1 to 1½ inches of the tube into the bladder. A second SF cystocatheter is inserted into the bladder approximately 2 cm. lateral to the first one by the same method. The tubes are secured to the skin with silk sutures. The anal sphincter is localized by inserting a finger into the rectum. Two insulated copper§ or platinum wiresll are inserted into the anal sphincter. Similar wires are inserted into the urethral sphincter (fig. 1). In boys the transperineal route is used. The needle with a curved wire is introduced through the perineum to the area of the apex of the prostate gland. A finger in the rectum guides the direction of the needle. The wire is engaged into the periurethral muscle and the needle is withdrawn. In girls the needles are introduced paraurethrally for 1 to 2 cm. and the position of the wires is checked by
t Dow Corning Corp., Midland, Michigan 48640. § Locally made. II Wire electrode, No. 13K71, DISA Electronics.
53I TABLE
1. Clinical rnaterial No. Pts.
N eurogenic bladder Pseudoneurogenic bladder (incontinence and recurrent urinary tract infection) Urinary tract reconstruction and undiversion Non-neurogenic incontinence (organic disorders and anomalies) Nocturnal enuresis Total
68 83 38 41
7 237
sit on a commode and void into an vum;;.»cc flovvmeter and stand to Yoid. A portable C-arm x-ray unit is positioned to an oblique view of the bladder neck and urethra (fig. 2). After appropriate recalibration of the instrument the bladder is filled slowly at 10 ml. per minute with hypaque solution. The bladder is provoked by coughing or the V alsalva maneuver. This allows bladder stability as well as competence of the bladder neck mechanism to be evaluated. Rapid bladder filling at a rate of 50 ml. per minute and subcutaneous injection of bethanechol chloride (1.25 mg. for children between 5 and 10 years and 2.5 mg. for children > 10 years old) are used to test further bladder stability. The bladder is filled several times until reproducible results are obtained. Simultaneous fluoroscopic monitoring and measurements of intravesical pressure, intra-abdominal pressure, sphincter electromyography and urine flow rate are recorded throughout bladder filling and during voiding (fig. 3). The urodynamic study must address the following basic questions: 1) Is the bladder stable or unstable? 2) Is the bladder neck mechanism competent or incompetent at rest? 3) Is the bladder neck mechanism synchronous with detrusor contractions or is it dyskinetic? 4) Does the distal sphincter mechanism exhibit uninhibited relaxations or contractions? 5) Does the distal sphincter mechanism relax normally during voiding or is it dyssynergic? The first few voiding tracings allow the child to adjust to the test conditions so that subsequent voidings are generally more meaningful and consistent than the early studies. A pilot study to test the effect of an indwelling urechral catheter on flow rates was performed in 10 children between 9 and 14 years old. Urine flow rates were recorded with and without an indwelling SF catheter in the urethra. The bladder was filled with normal saline and the child was instructed to urinate around the catheter into the flowmeter. The urine flow rate was compared to a subsequent flow rate obtained during the voiding study 24 hours later, when the urethra was free of a catheteL An additional study was done to compare the electrical activity of the urethral and perianal sphincters in 38 children who had wires inserted into the periurethral and perianal -·u'i-uf..-::•.•;:;'~~;;•H tracings were obtained in 11 and 13 girls. RESULTS AND COMMENTS
FIG. 1. Cystocatheters in bladder and electromyography electrodes in periurethral and perianal sphincter.
introducing the panendoscope in the mid urethra and the wire. Recently, insertion of wires into the anal has been omitted and monitoring of the electrical the urethral sphincter is performed exclusively. The next after the effect of anesthesia has worn off and the child has become accustomed to the cystocatheters and wires, he or she returns to the urodynamic unit for a voiding study fully alert and psychologically prepared for the testing, knowing in advance that no further painful procedures are to be anticipated. A water-filled catheter,* placed high in the rectum well above the anal sphincter, is connected to a transducer. The intrarectal pressure balloon reflects changes in intra-abdominal pressure. The bladder is then filled with 15 per cent hypaque solution via 1 cystocatheter. The other cystocatheter is connected to a pressure transducer placed level with the pubic symphysis and intravesical pressure is recorded. A subtraction unit in the instrument provides the net detrusor pressure by subtracting the intra-abdominal from the total intravesical pressure. Girls *
American Medical System, DGC-50.
The full urodynamic evaluation was completed in most children in 3 days. There was no mortality in this series. The complications of the are summarized in table 2. Bleeding occurred from the bladder site in 2 children, of whom l responded to bladder u,;uu,.v"' and the other underwent fulguration of a ""''u,w,,; vessel at the entrance of the into the anterior extrava"'"'"1,,,np.rt in 2 resulting in a.uuu•1u111
532
HANNA AND ASSOCIATES
FIG. 2. Ten-year-old girl undergoing urodynamic study URODYNAMIC EVALUATION OF THE LOWER URINARY TRACT
SPHINCTER ELECTROMYOGRAPHY
INTRAVESICAL
A
PRESSURE
INTRA-ABDOMINAL
B
PRESSURE
A-8: Oetrusor Pr111ur1
V
VOIDING CYSTO- URETHROGRAPH
FLOW RATE
FIG. 3. Schematic representation of synchronous recording of subtracted detrusor pressure, urine flow rate, sphincter electromyography and voiding cystourethrography. TABLE
2. Morbidity ofurodynamics (237 children) No.(%)
Bleeding: Blood transfusion Fulguration Extravasation resulting in ileus Total
TABLE
Maximum Flow Rate
3. Urine flow rate
Av. Flow Rate
Flow
With catheter 1 1 2 4 (1.7)
hinderance to urine flow in most of the children tested (table 3). These data support our contention that the suprapubic puncture method is superior to catheters placed per urethram and lends itself to studies with the least possible artifact. Some may argue that bladder puncture might result in detrusor irritability manifesting with uninhibited contractions. However, when cystometric tracings via a suprapubic catheter were compared to the original urethral catheter study that was normal no uninhibited contractions were detected. Table 4 shows that the urethral and anal sphincters are dissociated in their reflex activity, particularly in children with neuropathic bladder dysfunction. The functional dissociation between the 2 sphincters suggests that anal sphincter electromyography is unreliable. 6 • 7 Therefore, we have abandoned anal sphincter electromyography for diagnostic purposes. It should be emphasized that electromyography generally is the most demanding aspect of the study and great efforts must be made to minimize artifact.
12 7 7.5 7.5 8 5 7 8 10 5
10 5 6 4 5 2.5 5 7.5 7.5 3
Normal Intermittent Intermittent Normal Intermittent Intermittent Intermittent Normal Intermittent Intermittent
Without catheter 14 13 15 11
16 5 12.5 10 15 12.5
11 10 12 9 12 3 9 8 12.5 10
Normal Normal Normal Normal Normal Intermittent Intermittent Normal Normal Intermittent
We conclude that an electronic apparatus provides an objective method of studying micturition in children and is superior to static recordings of a dynamic event. Diagnostic accuracy and therapeutic measures are enhanced greatly by this much
URODYNAMICS IN CHILDREN TABLE
4. Urethral and anal sphincter electromyography in 24
children
Identical Complete dissociation Totals
Non-Neurogenic Bladder Dysfunction
N eurogenic Bladder
10
8
2 12
4
12
2. 3. 4. 5.
more sophisticated approach to the pathophysiology of dysfunctional states of the lower urinary tract in children. REFERENCES 1. Blaivas, J. G., Labib, K. L., Bauer, S. B. and Retik, A. B.: Changing
6. 7.
concepts in urodynamic evaluation of children. J. Urnl., 117: 778, 1977. Allen, T. D. and Bright, T. C., III: Urodynamic patterns in children with dysfunctional voiding problems. J. Urol., 119: 247, 1978. Firlit, C. F. and Cook, W. A.: Voiding pattern abnormalities in children. Urology, Hl: 25, 1977. Hanna, M. K.: Review of fundamental urodynamics in children. Urology, 15: 630, 1980. Kroovand, R. L., Reiner, R. J. and Perlmutter, A. D.: Trocar suprapubic cystotomy in pediatric urology: its advantages and pitfalls. Read at annual meeting of American Urological Association, New York, New York, May 13-17, 1979. Hald, T.: Personal communication. Vereecken, R. L. and Verduyn, H.: The electrical activity of the paraurethral and perinea! muscles in normal and pathologic conditions. Brit. J. Urol., 42: 457, 1970.
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright© 1981 by The Williams & Wilkins Co.
Urological Neurology and Urodynamics URODYNAMICS IN CHILDREN. PART I. METHODOLOGY MONEER K. HANNA,* WILLIAM DI SCIPIO, KYOUNG K. SUH, STANLEY J. KOGAN, SELWYN B. LEVITT AND KENNETH DONNER From the Division of Pediatric Urology, Children's Hospital of New Jersey, Newark, New Jersey, and Division of Pediatric Urology, and Departments of Anesthesia and Psychiatry, Hospital of the Albert Einstein College of Medicine and Montefiore Hospital and Medical Center, Bronx, New York
ABSTRACT
We evaluated 237 children for various urologic disorders in the urodynamic laboratory. A total of 334 studies was done, using a 6-channel recordert combined with a portable fluoroscopic unit. Simultaneous recordings of intravesical pressure, intra-abdominal pressure, urine flow rate, external urethral electromyography and cystourethrography were obtained during bladder filling and voiding. These objective tests have provided us with an insight into the nature of a variety of voiding dysfunctions in children. Details of the methods used for urodynamic testing in these children are outlined and compared to other methods that have been proposed. Dynamic studies of the lower urinary tract in adults have been discussed extensively. The application and adaptation of urodynamic testing of children have gained acceptance recently as a clinical rather than a research modality. 1- 4 It has become clear that measurements of isolated events during bladder filling or voiding result in erroneous interpretations. Dynamic studies provide the opportunity to study micturition continuously during all of its phases, allowing for more accurate identification of pathophysiologic events. Herein we report on the simultaneous recordings of the various functional parameters of the lower urinary tract in children. The methodology is described in detail. It has been designed especially for children and avoids all painful stimuli on the day of the urodynamic test. Anxiety and discomfort produce artifacts that render the study results uninterpretable. MATERIALS AND METHODS
Selection of patients. Early in our experience urociynamic studies were reserved for a select group of children who were either frequently infected and/or incontinent, despite continuous antibacterial therapy, empiric pharmacologic manipulation and urethral dilation. The excellent results of therapy directed by the urodynamic testing in this recalcitrant group of children who had failed to respond to conventional therapy prompted us to become more liberal with our indications for the tests (table 1). Currently, all children with persistent voiding symptoms or those who become infected while on continuous antibacterial therapy are studied. Children with clinical neuropathy, as well as those who are candidates for urinary undiversion, are investigated routinely. We do not study nocturnal enuretics but we obtain measurements of the urine flow rate in an outpatient setting. Initial evaluation. Following completion of the standard urologic studies, including history, physical examination, urinalysis and culture, excretory urography with upright anteroposterior and oblique films of the bladder base and a voiding cystourethrogram, an outpatient flow rate is obtained. The Accepted for publication July 14, 1980. * Address for reprints: Children's Hospital of New Jersey, 15 South Ninth St., Newark, New Jersey 07107. t Rack version of DISA urological investigation system, DISA Electronics, Franklin Lakes, New Jersey 07 417. 530
child and parents are then interviewed simultaneously with a pediatric urologist and a child psychologist. The urodynamic procedure, its implications and the information being sought from the tests are explained carefully to the parents and child. Psychological assessment of the child and family is conducted to identify any source of maladaptive anxiety, as well as to help establish appropriate coping strategies. A videotape of the urodynamic procedure, showing an age-appropriate child, is reviewed with the family and is followed by a discussion with the psychologist. Neurological evaluation is done, the x-rays are reviewed and a plan is made for urodynamic testing. All medications that may affect bladder and urethral functions are discontinued 1 week before admission to the urodynamic unit. The day in the hospital also allows documentation of the child's voiding habits and pattern. Urodynamic testing. Pre-anesthetic medications are deliberately not given. The child urinates into the flowmeter and is then catheterized. The residual urine is recorded. Conventional gas cystometry, provocative cystometry and urethral pressure profilometry are done in older and more cooperative children before the induction of anesthesia. Thereafter, cystourethroscopy is performed with the child under general anesthesia. Under direct cystoscopic control the full bladder is palpated and a trocar is introduced into the bladder. When there is fluid return an SF cystocathetert is advanced through the sheath under direct vision panendoscopic control. We then insert 1 to 1½ inches of the tube into the bladder. A second SF cystocatheter is inserted into the bladder approximately 2 cm. lateral to the first one by the same method. The tubes are secured to the skin with silk sutures. The anal sphincter is localized by inserting a finger into the rectum. Two insulated copper§ or platinum wiresll are inserted into the anal sphincter. Similar wires are inserted into the urethral sphincter (fig. 1). In boys the transperineal route is used. The needle with a curved wire is introduced through the perineum to the area of the apex of the prostate gland. A finger in the rectum guides the direction of the needle. The wire is engaged into the periurethral muscle and the needle is withdrawn. In girls the needles are introduced paraurethrally for 1 to 2 cm. and the position of the wires is checked by
t Dow Corning Corp., Midland, Michigan 48640. § Locally made. II Wire electrode, No. 13K71, DISA Electronics.
53I TABLE
1. Clinical rnaterial No. Pts.
N eurogenic bladder Pseudoneurogenic bladder (incontinence and recurrent urinary tract infection) Urinary tract reconstruction and undiversion Non-neurogenic incontinence (organic disorders and anomalies) Nocturnal enuresis Total
68 83 38 41
7 237
sit on a commode and void into an vum;;.»cc flovvmeter and stand to Yoid. A portable C-arm x-ray unit is positioned to an oblique view of the bladder neck and urethra (fig. 2). After appropriate recalibration of the instrument the bladder is filled slowly at 10 ml. per minute with hypaque solution. The bladder is provoked by coughing or the V alsalva maneuver. This allows bladder stability as well as competence of the bladder neck mechanism to be evaluated. Rapid bladder filling at a rate of 50 ml. per minute and subcutaneous injection of bethanechol chloride (1.25 mg. for children between 5 and 10 years and 2.5 mg. for children > 10 years old) are used to test further bladder stability. The bladder is filled several times until reproducible results are obtained. Simultaneous fluoroscopic monitoring and measurements of intravesical pressure, intra-abdominal pressure, sphincter electromyography and urine flow rate are recorded throughout bladder filling and during voiding (fig. 3). The urodynamic study must address the following basic questions: 1) Is the bladder stable or unstable? 2) Is the bladder neck mechanism competent or incompetent at rest? 3) Is the bladder neck mechanism synchronous with detrusor contractions or is it dyskinetic? 4) Does the distal sphincter mechanism exhibit uninhibited relaxations or contractions? 5) Does the distal sphincter mechanism relax normally during voiding or is it dyssynergic? The first few voiding tracings allow the child to adjust to the test conditions so that subsequent voidings are generally more meaningful and consistent than the early studies. A pilot study to test the effect of an indwelling urechral catheter on flow rates was performed in 10 children between 9 and 14 years old. Urine flow rates were recorded with and without an indwelling SF catheter in the urethra. The bladder was filled with normal saline and the child was instructed to urinate around the catheter into the flowmeter. The urine flow rate was compared to a subsequent flow rate obtained during the voiding study 24 hours later, when the urethra was free of a catheteL An additional study was done to compare the electrical activity of the urethral and perianal sphincters in 38 children who had wires inserted into the periurethral and perianal -·u'i-uf..-::•.•;:;'~~;;•H tracings were obtained in 11 and 13 girls. RESULTS AND COMMENTS
FIG. 1. Cystocatheters in bladder and electromyography electrodes in periurethral and perianal sphincter.
introducing the panendoscope in the mid urethra and the wire. Recently, insertion of wires into the anal has been omitted and monitoring of the electrical the urethral sphincter is performed exclusively. The next after the effect of anesthesia has worn off and the child has become accustomed to the cystocatheters and wires, he or she returns to the urodynamic unit for a voiding study fully alert and psychologically prepared for the testing, knowing in advance that no further painful procedures are to be anticipated. A water-filled catheter,* placed high in the rectum well above the anal sphincter, is connected to a transducer. The intrarectal pressure balloon reflects changes in intra-abdominal pressure. The bladder is then filled with 15 per cent hypaque solution via 1 cystocatheter. The other cystocatheter is connected to a pressure transducer placed level with the pubic symphysis and intravesical pressure is recorded. A subtraction unit in the instrument provides the net detrusor pressure by subtracting the intra-abdominal from the total intravesical pressure. Girls *
American Medical System, DGC-50.
The full urodynamic evaluation was completed in most children in 3 days. There was no mortality in this series. The complications of the are summarized in table 2. Bleeding occurred from the bladder site in 2 children, of whom l responded to bladder u,;uu,.v"' and the other underwent fulguration of a ""''u,w,,; vessel at the entrance of the into the anterior extrava"'"'"1,,,np.rt in 2 resulting in a.uuu•1u111
532
HANNA AND ASSOCIATES
FIG. 2. Ten-year-old girl undergoing urodynamic study URODYNAMIC EVALUATION OF THE LOWER URINARY TRACT
SPHINCTER ELECTROMYOGRAPHY
INTRAVESICAL
A
PRESSURE
INTRA-ABDOMINAL
B
PRESSURE
A-8: Oetrusor Pr111ur1
V
VOIDING CYSTO- URETHROGRAPH
FLOW RATE
FIG. 3. Schematic representation of synchronous recording of subtracted detrusor pressure, urine flow rate, sphincter electromyography and voiding cystourethrography. TABLE
2. Morbidity ofurodynamics (237 children) No.(%)
Bleeding: Blood transfusion Fulguration Extravasation resulting in ileus Total
TABLE
Maximum Flow Rate
3. Urine flow rate
Av. Flow Rate
Flow
With catheter 1 1 2 4 (1.7)
hinderance to urine flow in most of the children tested (table 3). These data support our contention that the suprapubic puncture method is superior to catheters placed per urethram and lends itself to studies with the least possible artifact. Some may argue that bladder puncture might result in detrusor irritability manifesting with uninhibited contractions. However, when cystometric tracings via a suprapubic catheter were compared to the original urethral catheter study that was normal no uninhibited contractions were detected. Table 4 shows that the urethral and anal sphincters are dissociated in their reflex activity, particularly in children with neuropathic bladder dysfunction. The functional dissociation between the 2 sphincters suggests that anal sphincter electromyography is unreliable. 6 • 7 Therefore, we have abandoned anal sphincter electromyography for diagnostic purposes. It should be emphasized that electromyography generally is the most demanding aspect of the study and great efforts must be made to minimize artifact.
12 7 7.5 7.5 8 5 7 8 10 5
10 5 6 4 5 2.5 5 7.5 7.5 3
Normal Intermittent Intermittent Normal Intermittent Intermittent Intermittent Normal Intermittent Intermittent
Without catheter 14 13 15 11
16 5 12.5 10 15 12.5
11 10 12 9 12 3 9 8 12.5 10
Normal Normal Normal Normal Normal Intermittent Intermittent Normal Normal Intermittent
We conclude that an electronic apparatus provides an objective method of studying micturition in children and is superior to static recordings of a dynamic event. Diagnostic accuracy and therapeutic measures are enhanced greatly by this much
URODYNAMICS IN CHILDREN TABLE
4. Urethral and anal sphincter electromyography in 24
children
Identical Complete dissociation Totals
Non-Neurogenic Bladder Dysfunction
N eurogenic Bladder
10
8
2 12
4
12
2. 3. 4. 5.
more sophisticated approach to the pathophysiology of dysfunctional states of the lower urinary tract in children. REFERENCES 1. Blaivas, J. G., Labib, K. L., Bauer, S. B. and Retik, A. B.: Changing
6. 7.
concepts in urodynamic evaluation of children. J. Urnl., 117: 778, 1977. Allen, T. D. and Bright, T. C., III: Urodynamic patterns in children with dysfunctional voiding problems. J. Urol., 119: 247, 1978. Firlit, C. F. and Cook, W. A.: Voiding pattern abnormalities in children. Urology, Hl: 25, 1977. Hanna, M. K.: Review of fundamental urodynamics in children. Urology, 15: 630, 1980. Kroovand, R. L., Reiner, R. J. and Perlmutter, A. D.: Trocar suprapubic cystotomy in pediatric urology: its advantages and pitfalls. Read at annual meeting of American Urological Association, New York, New York, May 13-17, 1979. Hald, T.: Personal communication. Vereecken, R. L. and Verduyn, H.: The electrical activity of the paraurethral and perinea! muscles in normal and pathologic conditions. Brit. J. Urol., 42: 457, 1970.