- Email: [email protected]
The Non-Neurogenic Neurogenic Bladder
THE JOURNAL
Vol. 117, February Printed in U.S.A.
OF UROLOGY
Copyright © 1977 by The Williams & Wilkins Co.
Pediatric Articles THE NON-NEUROGENIC NEUROGENIC BLADDER TERRY D. ALLEN From the Division of Urology, The University of Texas, Southwestern Medical School, Dallas, Texas
ABSTRACT
The records of 21 children with neuropathic bladder disease are reviewed. The natural history in these cases has been consistent with that of an acquired disorder and the results of urodynamic testing have supported Hinman's contention that the disease is basically a functional one, caused by a discoordination between detrusor contraction and sphincter relaxation. Bladder retraining and specific medication have yielded far better results than were obtained previously by surgical measures alone. although she could generate a sustained flow on voiding as high as 17 cc per second. She was placed on catheter drainage with improvement in the blood chemistry studies but each effort to remove the catheter was associated with biochemical deterioration. Finally, ileal conduit urinary diversion was undertaken but within 9 months renal function had deteriorated to the point that hemodialysis became necessary. Subsequently, the patient underwent renal transplantation but died the following year during an episode of severe rejection. Comment: The inexorable course of this disease in the face of aggressive therapy was frustrating to all concerned but we were convinced from the anatomical and neurological investigations that had been done that the child did not suffer from mechanical obstruction or organic neurological disease in the usual sense. It was this case that stimulated us to consider detrusor-sphincter dyssynergia as a possible explanation for the disorder and prompted us to direct future investigative efforts toward the resolution of this question. Case 2. I. S., a white girl, was first seen when she was 3 years old because of unusual urinary habits manifested by alternating periods of infrequent voiding and periods of frequency with urgency to the point of incontinence. A voiding cystourethrogram and IVP were considered normal, and cystoscopy CASE REPORTS revealed only mild trabeculation of the bladder. The child Case 1. E. M., a Latin-American girl, was first evaluated for reappeared 7 years later with the complaints of involuntary urinary tract infection when she was 4 years old. An excretory wetting and foul smelling urine, and 800 cc of infected residual urogram (IVP) showed a large bladder and grade I ectasia of urine was recovered from the bladder. A cystogram revealed a the right collecting system (fig. 1, A). Initially, she was treated large capacity heavily trabeculated bladder (fig. 2, A) and IVP conservatively but because of continuing infection and radio- (fig. 2, B) demonstrated bilateral hydronephrosis but blood graphic deterioration of the upper urinary tract, a Y-V plasty of chemistry studies were within normal limits. It was noted, howthe bladder neck was done. At the time of this second ever, that the girl was sullen, suspicious and almost hostile. A hospitalization comment was made on the fact that the child social history disclosed that her father was dead and that her was wet much of the time and that the colon always contained mother was a severe alcoholic who literally abandoned the children at times to fend for themselves. Cystoscopy and neurolarge amounts of fecal material. The patient was lost to followup and not seen again until 11 logical evaluation failed to uncover any cause for her inability years later when she presented to the hospital with a blood urea to empty the bladder, while a urethral profile examination nitrogen of 137 mg. per cent. A cystogram revealed a large showed the point of highest pressure to be in the mid-urethral heavily trabeculated bladder (fig. 1, B), while retrograde zone, consistent with the location of the external urethral pyelography outlined thin renal shells bilaterally. No obstruc- sphincter. A cystometrogram after 2 weeks of catheter drainage tion could be identified cystoscopically and a thorough neuro- revealed elevated intravesical pressure and a sudden violent logical examination was negative. A cystometrogram revealed contraction of the bladder at 275 cc volume at which time a a bladder pressure that exceeded 100 cm. water at a 450 cc pressure in excess of 90 cm. water was recorded. Anal sphincter volume but the patient was unable to empty the bladder, electromyography during voiding indicated that not only did the patient fail to relax the sphincter at the time of micturition but also that the sphincter activity actually increased paradoxAccepted for publication June 18, 1976. There is a group of children who exhibit all of the features of a severe obstructive uropathy (heavily trabeculated bladder, elevated residual urine, hydronephrosis and so forth) yet in whom neither anatomical obstruction nor neurological disease can be documented. The names applied to these cases (subclinical 1 or occult 2 neurogenic bladder, neuropathic bladder" and so forth 4) suggest that the disorder may be the result of some isolated neurological defect in which altered micturition appears as the only evidence of the disease. However, Hinman and Baumann have argued that the condition is not owing to organic neurological disease at all but rather to a functional discoordination between detrusor contraction and sphincter relaxation. 5 ' 6 Our experience with more than 20 of these patients has led us to the same conclusion, namely that this syndrome is the result of functional, not organic, factors. Nonetheless, this concept has not received widespread recognition in urology and the disease continues to be treated by methods that are often as potentially destructive as they are ineffective. Therefore, it seems appropriate to present our experience with this problem in order to add further support to Hinman's thesis and to show the favorable response that can be achieved in this disorder with conservative measures.
232
NON-NEUROGENIC NEUROGENlC BLADDER
233
FIG. L Case 1. A, IVP in 4-year-old girl. B, cystogram when patient was 15 years old. There was non-visualization of upper urinary tracts on IVP at this time.
FIG. 2. Case 2. A, cystogram and B, IVP in 10-year-old girl with 800 cc residual urine. C, IVP 2 two years later after treatment
ically during the effort. As a consequence of this discoordination, urination was intermittent and interrupted rather than sustained. A concerned aunt assumed the major for the care of the child and a clinical psychologist was incorporated into the management team, while a program of bladder retraining was instituted. Nonetheless, 3 months passed before the patient was able to get by without a catheter and nearly 2 years before the urine could be maintained completely free of bacteria. An IVP at the end of that time demonstrated improvement in the anatomy of the urinary tract (fig. 2, C). The patient is currently asymptomatic, h1c:s sterile urine and residual urine is less than 20 cc. Comment: This case provided us with the first positive evidence of detrusor-sphincter dyssynergia as an etiological factor in the development of this disorder. It also convinced us of the efficacy of a bladder retraining program. Case 3. D. M., the younger sister of E. M. (case 1), was evaluated when she was 12 years old because of lower abdominal cramps and infrequent urination associated with marked urgency. The urine was infected and the cystogram (fig. 3, A)
was remarkably similar to that of her sister (fig. 1, while the IVP showed bilateral Hffr~·,,n~ (fig, 3, B). The child was almost uncommunicative, although superficially cooperative. A social history of the family indicated that the mother was an anxious but inadequate person incapable of handling complex problems and that the father was a rather dull individual who disappeared for days at a time, presumably on drinking sprees, leaving the family to handle matters as best they could. In the evaluation of the child cystoscopy and neurological examination were once again non-informative, while cystometry revealed high intravesical pressure and a powerful involuntary detrusor contraction associated with voiding around the catheter at a volume of 450 cc. The patient was able to void with a sustained stream but anal sphincter electromyography indicated that she did so without concomitant relaxation of the perineum. The child was placed on Foley catheter drainage and seen by a clinical psychologist who unsuccessfully attempted hypnosis. Bladder retraining was started but it was 4 months before the patient was completely free of the catheter and, during this period, residual urines ran as high as 500 cc. She also had 1
234
ALLEN
FIG. 3. Case 3. A, cystogram and B, IVP in 12-year-old girl with lower abdominal cramps and urgency incontinence. C, IVP 1 year later after treatment.
episode with a fecal impaction manifested by a palpable lower abdominal mass. Ultimately, however, clear urine and residuals of less than 90 cc were achieved with bladder retraining, dantrolene sodium, stool softeners and sulfamethoxazoletrimethoprim. At the present time the residual urine is zero, the child's personality has changed (she is now more warm and outgoing) and a followup IVP shows considerable improvement in the status of the urinary tract (fig. 3, C). Case 4. C. D., a 12-year-old white boy, gave a long history of diurnal wetting and encopresis. He also admitted to abdominal cramps associated with a sensation of a need to void but stated that if he waited momentarily the pain would pass and he could resume playing. No one had ever advised him to do differently. The urinary tract problem finally surfaced when the patient began running a fever and was found to have infected urine. An IVP was normal except for excessive residual urine and a cystogram showed a large capacity smooth walled bladder with bilateral vesicoureteral reflux (fig. 4). Cystoscopy and neurological examination failed to uncover any subvesical obstruction or neurological disease. However, urodynamic studies showed that the child was unable to void on command; instead, he waited until bladder filling initiated an involuntary
detrusor contraction and then voided by relaxing the perinea! musculature. Since this occurred only intermittently and for momentary periods, urination was characterized by short bursts with high flow. Residual urine was 700 cc. The patient was started on bladder retraining and imipramine hydrochloride, and the wetting and fecal soiling ceased almost immediately. At the 3-month followup the residual urine was down to 220 cc and, although the child still tended to void in short explosive bursts, he was now able to initiate the stream upon command. At 5 months the residual urine was only 50 cc. The patient was then lost to followup momentarily but was located and seen again 4 months later, at which time it was discovered that he had run out of imipramine hydrochloride, that he was wetting himself again and that the residual urine had risen to 145 cc. Additional history revealed that he had entered junior high school where the first floor bathrooms were locked because of vandalism so that he had to go to the third floor to urinate. Since the child had only a few minutes between classes and since he had been advised that he would receive a detention if he were late to his next class, the voiding was necessarily rushed. lmipramine hydrochloride was resumed and the principal was contacted to enlist his cooperation with the problem.
235
NOJ:-I-h[EUROGENIC
Comment: ,ucwJ•-,;;u smooth on the cystogram, this was afflicted with the same problem as the other children in the series. Not all of these bladders have the characteristic Christmas tree appearance considered so typical of this disorder. This case also demonstrated the importance of close and in the management of these problems. CLINICAL MATERIAL
Within the last decade we have encountered 21 children with evidence of a severe obstructive uropathy in the absence of an anatomical or neurological explanation to account for it. All of these patients exhibited radiographic abnormalities of the urinary tract and all demonstrated failure to empty the bladder on multiple occasions. Clinical features. There were 13 and 8 girls ranging in age from 2 ½ to 12 years. Hm:vever, 7 these children, 2 ½ to 6 years old, were not recognized as having this problem when first seen and, in fact, the radiograms at the time of their initial visits were normal in 4. The most severe disease was seen in those children between 7 and 12 years old, while in 2 patients spontaneous resolution of the voiding abnormality occurred after puberty. The picture presented by these children thus has been that of an acquired disorder, first becoming manifest at some point after the potty training period, reaching its peak of destructiveness in late childhood and showing some tendency to resolution after
rnost aspect of the clinical has been vvetness, vvhich v,,ras seen in_ 19 of the 21 children and occurred diurnally as well as in most. In some this assumed the character of urge incontinence and was associated with detectable in the lower abdomen. In others it occurred more or less without apparent awareness on the part of the child. Some voided and others voided infrequently but most voided in an intermittent or interrupted manner. A sustained stream of good volume was unusual. For the most part it appeared that normal voiding patterns had never been established in these patients rather than that established voiding patterns had regressed. Many of these children also exhibited bowel dysfunction manifested by encopresis, chronic constipation with infrequent bulky stoois or even fecal impactions sufficient to produce a palpable mass in the lower abdomen. While information relative to bowel dysfunction was not always sought, the response was positive in 9 of the 13 patients in whom the question was raised. In 19 children the urine also was infected, although the infection in a clinical sense was seldom impressive. Few patients exhibited high fever or sepsis and often the clinical picture of infection was put together in retrospect after the urinary findings had come to light. The social history proved to be a particularly important part of the evaluation of these children since it often provided insight into factors of potential etiologic significance. For alcoholism was rampant in the family of 4 of those
FIG. 4. Case 4. Cystogram in 12-year-old boy with urgency incontinence and 700 cc residual urine
236
ALLEN
with severe voiding dysfunction, while divorces created signifi- recordert and intravesical pressure, flow rate and perinea] cant problems in several others. In 3 cases the father was noted muscle activity are measured simultaneously during the act of to be a dominant figure who verbally emasculated the child voiding. Repeated runs are made until reproducible results are with every word he spoke, while the mother remained passive obtained. to the point of being obsequious. Abnormalities in the perFrom these studies it has become quite apparent that sonalities of the children also were noticeable in many in- intravesical pressures are abnormally high in these children stances. Some were shy and withdrawn as though over- and that detrusor contractility is not only intact, it is hyperrewhelmed by the circumstances of their environment and others sponsive. The discoordination that exists between the detrusor were openly hostile. Several children demonstrated restless- and the sphincter has been clearly evident in the failure to ness and hyperactivity with short attention spans. This is not maintain pelvic relaxation during detrusor contraction as well to say that environmental or psychological factors could be as paradoxical contractions of the sphincter during efforts to identified in every case but they were striking in about half of void. The initial micturitional event in these children is usually them and undoubtedly could have been found in more had an a rise in intravesical pressure but despite a sustained elevation in this pressure, voiding itself occurs only upon relaxation of intensive search been made for them. Of the 21 patients 12 underwent 24 major operative proce- the pelvic floor and this is often unpredictable and of momendures at some point during the course of their disease. These tary duration. Thus, the flow tends to be intermittent and included 6 Y-V plasties of the bladder neck, 16 ureteral interrupted, and occasionally consists of short bursts of exploreimplantations (of which 5 failed) and 4 ilea! conduit urinary sive force. A rare patient has even been able to maintain a diversions, 1 of which was undiverted subsequently. There sustained stream without complete pelvic relaxation simply by were also 1 renal transplantation, 1 pyeloplasty, 1 ureteral re- developing an intravesical pressure so high as to overpower the section and 1 transureteroureterostomy. A critical analysis of sphincter. However, the pattern has been quite variable, even this group indicates that most of these procedures were either in the same patient (fig. 5), which further suggests that the unnecessary or ill-advised. discoordination is functional and not organic in origin. Objective features. Among the objective features of the Management. Because of our conviction that the non-neurodisorder the most consistent abnormality has been the appear- genic neurogenic bladder is a functional disorder in which there ance of the bladder. Typically, the bladder is of large capacity, is failure to coordinate the activities of 2 separate muscle heavily trabeculated and empties poorly. In only 2 cases did groups, we found it reasonable to believe that the disease could the bladder seem smooth walled on the cystogram and in both be overcome through a process of re-education or retraining. instances it was described as trabeculated at cystoscopy. In 2 When decompensation of the urinary tract has threatened the other patients the bladder, while heavily trabeculated, was of life of the patient catheter drainage has been used initially as a normal volume. Residual urine was documented in every case temporizing measure, otherwise the retraining program begins and in several patients the bladder was readily palpable at the time of the urodynamic evaluation of the child. In the suprapubically. Vesicoureteral reflux, usually bilateral, was presence of the parents repeated runs are made during which demonstrated in 12 patients but in 4 of them this finding was the child is encouraged to relax the perineum and maintain a not present on earlier available cystograms, suggesting that sustained stream without straining. By monitoring these events reflux in these cases may have been an acquired phenomenon the child can be directed in these efforts; indeed he can see the secondary to intravesical pressures, which were chronically results for himself on the recorder as he performs. This initial elevated. In several instances spontaneous disappearance of session sets the pattern for future practice sessions at home the reflux occurred when effective conservative treatment was and, upon discharge from the hospital, the patient is instructed instituted. to void every 3 hours or so while awake, to go to the bathroom Bilateral hydronephrosis was present in 14 patients and in 3 promptly whenever the sensation of a need to void arises and to others renal parenchymal scars were seen as a result of reflux set aside ample time for voiding so that the act is never rushed and infection. Thus, only 4 patients in the entire series had or performed under pressure. At the same time the child is innormal upper urinary tracts. However, of the 17 patients with structed to make sure that every effort is made to eliminate all upper urinary tract damage 5 had had normal x-rays initially of the urine from the bladder even if this requires multiple and it was only as the process unfolded that renal destruction voidings. Continued parental encouragement, rewards, perbegan to develop. Biochemical confirmation of renal damage sonal progress charts and so forth serve to remind the child of was available in most of those children with abnormal x-rays the goals desired. The children often are catheterized for reand in 5 cases renal functional impairment was severe. One sidual urine when they return for their followup visit, compatient required renal transplantation, 1 is currently on parisons are made with previous performance records and the hemodialysis and 3 others have advanced renal failure and are problem is discussed with the child and the family to uncover the explanation for any setbacks. Parental understanding and awaiting entry into the transplant program. Urodynamic features. The most definitive information rela- support are essential for success and, when indicated, profestive to the nature of the problem in these children has come sional psychological counseling for the family or child is sought. out, not from static studies, but from dynamic ones. Originally, Medication also has played an important role in the over-all we studied detrusor-sphincter coordination by placing elec- management of these patients, particularly imipramine hydrotromyographic electrodes in the anal sphincter of awake chloride, which has been quite effective in stopping wetness patients and reading the pattern of muscular activity directly and often fecal soiling as well. This response, by serving as an from the oscilloscope. Unfortunately, this is rather uncomfort- immediate indicator of improvement, also encourages the child able to the patient and requires a greater measure of coopera- to have confidence in the ultimate success of the treatment. tion than can be obtained easily in small children. Further- Bethanechol chloride has been helpful in lowering the residual more, it provides no permanent record of the event. More urine in a few instances when the bladder is badly decompenrecently, we have been inserting 2 No. SF silicone catheters* sated, and dantrolene sodium and phenoxybenzamine hydropercutaneously into the bladder during the cystoscopic proce- chloride have been used occasionally, although with doubtful dure, while at the same time, small insulated wires are benefits. Stool softeners and enemas have been required as passed through a 25 gauge needle, hooked into the anal adjunctive measures in a number of instances and various sphincter and taped into place. Later the same day or the tranquilizers have been used on occasion to combat hyperactivfollowing morning the child is connected to a 3-channel ity and anxiety. In no instance, however, have such medica* Cystocath, Dow Corning Corp., Midland, Michigan. t Life-Tech Instruments, Inc., Houston, Texas.
NON-I\JEUROGENIC NEURO{}E:NIC: BLADDER
237
PRESSURE
~ so 25
f'LOW
FIG. 5. Urodynamic study in 4-year-old boy with short attention span shows 2 events. The child concentrated upon his efforts to maintain a sustained stream and managed to keep sphincter suppressed quite well (left arrow). On the next run, however, he lost interest in study and failed to coordinate voiding efforts so that the stream was interrupted (right arrow).
tions been intended to supplant bladder retraining, which remains the cornerstone of the management protocol. Careful followup has been an essential part of the program. Six months of close observation are believed to be the minimum necessary to ensure that no relapse occurs and in most cases a year or more is required before habit patterns are well established. It is comforting to note, however, that every child treated by this protocol has shown gradual but steady improvement clini<;ally and radiographically, and several cases have been considered cured. DISCUSSION
The belief that urinary tract damage of the magnitude described herein could arise from functional factors alone has been difficult for many to accept and more often than not the disorder has been attributed to an isolated neurological defect, which involves the bladder alone and which cannot be detected by the usual peripheral neurological examination. In support of this several authors have described weak sphincters, 1 • 2• 7 while others have reported evidence for partial vesical denervation. 3 Yet these same authors acknowledge the existence of vesical spasticity in these patients, although the simultaneous presence of vesical denervation and vesical spasticity would be paradoxical since the phenomena tend to be mutually exclusive. In our experience these bladders have been hyperactive, not weak, developing voiding pressures as high as 175 cm. water and often exhibiting involuntary contractions of great force. If these features suggest subvesical obstruction then the failure to identify an anatomical abnormality in these patients is understandably disturbing but it should not be forgotten that obstruction may exist in other forms. The external urethral sphincter, for example, is not simply a passive structure in micturition; it exerts constant pressure against the urethra at all times, even at rest, and is truly silent only during urination. 8 Thus, effective voiding requires the active suppression of all sphincter tone. Without this kind of coordination urination may be impeded if not prevented altogether, as so often is the case in the paraplegic. Therefore, it is not unreasonable to believe that the non-neurogenic neurogenic bladder might be but another manifestation of detrusorsphincter discoordination. In fact, our studies support this contention.
But why should these children fail to master such a simple basic function as urination? Could it be that some organic lesion exists within the reticular formation of the brain stem 9 or in the muscle spindles of the external urethral sphincter 10 impairing the coordination between the sphincter and detrusor? Along a similar vein it should be noted that Campbell and associates 11 found a high percentage of organic indicators during the psychological testing of enuretics and Fermaglich 12 has reported finding abnormal electroencephalograms in such children. Of course we cannot exclude an organic lesion entirely but the natural history of the disease, its variable pattern and its response to conservative measures, such as bladder retraining and hypnosis, do seem to be more consistent with a functional disease than an organic one. As we have become more aware of dysfunctional voiding as a pathological entity, we cannot help but notice the wide spectrum of disorders encompassed by this concept. Besides embracing the non-neurogenic neurogenic bladder at one extreme and enuresis at the other, it includes little girls with recurrent infection, 13 lazy bladders, 14 supervoiders 15 and dysfunctional syndromes of other types. One which has surfaced in the course of this particular study has been that in which secondary vesicoureteral reflux overshadows the underlying bladder dysfunction to the point that it appears as the primary pathology. Repeatedly, we have encountered patients with reflux in whom reimplantation of the ureters has failed to control either the reflux or the infection and in whom a dysfunctional bladder is finally identified at the heart of the problem. Clearly, in any child with vesicoureteral reflux, a hard look at the bladder for trabeculation, residual urine, incontinence or other evidence of detrusor-sphincter dyssynergia is an essential part of the evaluation. This conviction that the non-neurogenic neurogenic bladder is a functional disorder rather than some obscure neuropathic one has the distinct advantage that it makes the disease treatable. No longer should it be necessary to condemn these children empirically to permanent diversion of the urine and a lifetime of artificial appliances. Hinman and Baumann 5 used hypnosis successfully in the management of these problems, we have used bladder retraining, and Mulholland and associates 16 performed unilateral pudenda! nerve section in order to weaken the external urethral sphincter. However, this last approach would not appeal to us because 1) it uses a destructive procedure to correct a functional problem and 2) even unilat-
238
ALLEN
eral pudendal neurectomy may have adverse effects upon potency in the male subject. 17 Nonetheless, the realization that conservative measures can be effective should offer new hope to a small segment of our population who might otherwise face a progressively downhill course to permanent disability or death. Drs. George Hurt, Elgin Ware, Richard Harrison, David Resiman, Melvin Gross, Joe Rappaport, W. T. Snodgrass and Ted Boone allowed inclusion of their patients in this study. REFERENCES
1. Dorfman, L. E., Bailey, J. and Smith, J. P.: Subclinical neurogenic bladder in children. J. Urol., 101: 48, 1969. 2. Martin, D. C., Datta, N. S. and Schweitz, B.: The occult neurological bladder. J. Urol., 105: 733, 1971. 3. Williams, D. I., Hirst, G. and Doyle, D.: The occult neuropathic bladder. J. Pediat. Surg., 9: 35, 1974. 4. Kamhi, B., Horowitz, M. I. and Kovetz, A.: Isolated neurogenic dysfunction of the bladder in children with urinary tract' infection. J. Urol., 106: 151, 1971. 5. Hinman, F. and Baumann, F. W.: Vesical and ureteral damage from voiding dysfunction in boys without neurologic or obstructive disease. J. Urol., 109: 727, 1973. 6. Hinman, F.: Urinary tract damage in children who wet. Pediatrics, 54: 143, 1974.
7. Emmett, J. L. and Simon, H. B.: Transurethral resection in infants and children for congenital obstruction of the vesical neck and myelodysplasia. J. Urol., 76: 595, 1956. 8. Scott, F. B., Quesada, E. M. and Cardus, D.: Studies on the dynamics of micturition: observations on healthy men. J. Urol., \,2: 455, 1964. 9. Vinson, R. K. and Diokno, A. C.: Uninhibited neurogenic bladder in adults. Urology, 7: 376, 1976. 10. Bradley, W. E., Scott, F. B. and Timm, G. W.: .:,phincter electromyography. Urol. Clin. N. Amer., 1: 69, 1974. 11. Campbell, W. A., III, Weissman, M. and Lupp, J.: Bender Gestalt test and the urodynamics of enuresis. J. Urol., 104: 934, 1970. 12. Fermaglich, J. L.: Electroencephalographic study of enuretics. Amer. J. Dis. Child., 118: 473, 1969. 13. Tanagho, E. A., Miller, E. R., Lyon, R. P. and Fisher, R.: Spastic striated external sphincter and urinary tract infection in girls. Brit. J. Urol., 43: 69, 1972. 14. DeLuca, F. G., Swenson, 0., Fisher, J. H. and Loutfi, A.H.: The dysfunctional "lazy" bladder syndrome in children. Arch. Dis. Child., 37: 117, 1962. 15. Gleason, D. M., Bottaccini, M. R., Reilly, R. J. and Byrne, J.C.: The residual stream energy is a diagnostic index of male urinary outflow obstruction. Invest. Urol., 10: 72, 1972. 16. Mulholland, S. G., Yalla, S. V., Raezer, D. M. and Duckett, J. W., Jr.: Primary external urethral sphincter hyperkinesia in a boy. Urology, 4: 577, 1974. 17. Comarr, A. E.: Personal communication, 1976.
Vol. 117, February Printed in U.S.A.
OF UROLOGY
Copyright © 1977 by The Williams & Wilkins Co.
Pediatric Articles THE NON-NEUROGENIC NEUROGENIC BLADDER TERRY D. ALLEN From the Division of Urology, The University of Texas, Southwestern Medical School, Dallas, Texas
ABSTRACT
The records of 21 children with neuropathic bladder disease are reviewed. The natural history in these cases has been consistent with that of an acquired disorder and the results of urodynamic testing have supported Hinman's contention that the disease is basically a functional one, caused by a discoordination between detrusor contraction and sphincter relaxation. Bladder retraining and specific medication have yielded far better results than were obtained previously by surgical measures alone. although she could generate a sustained flow on voiding as high as 17 cc per second. She was placed on catheter drainage with improvement in the blood chemistry studies but each effort to remove the catheter was associated with biochemical deterioration. Finally, ileal conduit urinary diversion was undertaken but within 9 months renal function had deteriorated to the point that hemodialysis became necessary. Subsequently, the patient underwent renal transplantation but died the following year during an episode of severe rejection. Comment: The inexorable course of this disease in the face of aggressive therapy was frustrating to all concerned but we were convinced from the anatomical and neurological investigations that had been done that the child did not suffer from mechanical obstruction or organic neurological disease in the usual sense. It was this case that stimulated us to consider detrusor-sphincter dyssynergia as a possible explanation for the disorder and prompted us to direct future investigative efforts toward the resolution of this question. Case 2. I. S., a white girl, was first seen when she was 3 years old because of unusual urinary habits manifested by alternating periods of infrequent voiding and periods of frequency with urgency to the point of incontinence. A voiding cystourethrogram and IVP were considered normal, and cystoscopy CASE REPORTS revealed only mild trabeculation of the bladder. The child Case 1. E. M., a Latin-American girl, was first evaluated for reappeared 7 years later with the complaints of involuntary urinary tract infection when she was 4 years old. An excretory wetting and foul smelling urine, and 800 cc of infected residual urogram (IVP) showed a large bladder and grade I ectasia of urine was recovered from the bladder. A cystogram revealed a the right collecting system (fig. 1, A). Initially, she was treated large capacity heavily trabeculated bladder (fig. 2, A) and IVP conservatively but because of continuing infection and radio- (fig. 2, B) demonstrated bilateral hydronephrosis but blood graphic deterioration of the upper urinary tract, a Y-V plasty of chemistry studies were within normal limits. It was noted, howthe bladder neck was done. At the time of this second ever, that the girl was sullen, suspicious and almost hostile. A hospitalization comment was made on the fact that the child social history disclosed that her father was dead and that her was wet much of the time and that the colon always contained mother was a severe alcoholic who literally abandoned the children at times to fend for themselves. Cystoscopy and neurolarge amounts of fecal material. The patient was lost to followup and not seen again until 11 logical evaluation failed to uncover any cause for her inability years later when she presented to the hospital with a blood urea to empty the bladder, while a urethral profile examination nitrogen of 137 mg. per cent. A cystogram revealed a large showed the point of highest pressure to be in the mid-urethral heavily trabeculated bladder (fig. 1, B), while retrograde zone, consistent with the location of the external urethral pyelography outlined thin renal shells bilaterally. No obstruc- sphincter. A cystometrogram after 2 weeks of catheter drainage tion could be identified cystoscopically and a thorough neuro- revealed elevated intravesical pressure and a sudden violent logical examination was negative. A cystometrogram revealed contraction of the bladder at 275 cc volume at which time a a bladder pressure that exceeded 100 cm. water at a 450 cc pressure in excess of 90 cm. water was recorded. Anal sphincter volume but the patient was unable to empty the bladder, electromyography during voiding indicated that not only did the patient fail to relax the sphincter at the time of micturition but also that the sphincter activity actually increased paradoxAccepted for publication June 18, 1976. There is a group of children who exhibit all of the features of a severe obstructive uropathy (heavily trabeculated bladder, elevated residual urine, hydronephrosis and so forth) yet in whom neither anatomical obstruction nor neurological disease can be documented. The names applied to these cases (subclinical 1 or occult 2 neurogenic bladder, neuropathic bladder" and so forth 4) suggest that the disorder may be the result of some isolated neurological defect in which altered micturition appears as the only evidence of the disease. However, Hinman and Baumann have argued that the condition is not owing to organic neurological disease at all but rather to a functional discoordination between detrusor contraction and sphincter relaxation. 5 ' 6 Our experience with more than 20 of these patients has led us to the same conclusion, namely that this syndrome is the result of functional, not organic, factors. Nonetheless, this concept has not received widespread recognition in urology and the disease continues to be treated by methods that are often as potentially destructive as they are ineffective. Therefore, it seems appropriate to present our experience with this problem in order to add further support to Hinman's thesis and to show the favorable response that can be achieved in this disorder with conservative measures.
232
NON-NEUROGENIC NEUROGENlC BLADDER
233
FIG. L Case 1. A, IVP in 4-year-old girl. B, cystogram when patient was 15 years old. There was non-visualization of upper urinary tracts on IVP at this time.
FIG. 2. Case 2. A, cystogram and B, IVP in 10-year-old girl with 800 cc residual urine. C, IVP 2 two years later after treatment
ically during the effort. As a consequence of this discoordination, urination was intermittent and interrupted rather than sustained. A concerned aunt assumed the major for the care of the child and a clinical psychologist was incorporated into the management team, while a program of bladder retraining was instituted. Nonetheless, 3 months passed before the patient was able to get by without a catheter and nearly 2 years before the urine could be maintained completely free of bacteria. An IVP at the end of that time demonstrated improvement in the anatomy of the urinary tract (fig. 2, C). The patient is currently asymptomatic, h1c:s sterile urine and residual urine is less than 20 cc. Comment: This case provided us with the first positive evidence of detrusor-sphincter dyssynergia as an etiological factor in the development of this disorder. It also convinced us of the efficacy of a bladder retraining program. Case 3. D. M., the younger sister of E. M. (case 1), was evaluated when she was 12 years old because of lower abdominal cramps and infrequent urination associated with marked urgency. The urine was infected and the cystogram (fig. 3, A)
was remarkably similar to that of her sister (fig. 1, while the IVP showed bilateral Hffr~·,,n~ (fig, 3, B). The child was almost uncommunicative, although superficially cooperative. A social history of the family indicated that the mother was an anxious but inadequate person incapable of handling complex problems and that the father was a rather dull individual who disappeared for days at a time, presumably on drinking sprees, leaving the family to handle matters as best they could. In the evaluation of the child cystoscopy and neurological examination were once again non-informative, while cystometry revealed high intravesical pressure and a powerful involuntary detrusor contraction associated with voiding around the catheter at a volume of 450 cc. The patient was able to void with a sustained stream but anal sphincter electromyography indicated that she did so without concomitant relaxation of the perineum. The child was placed on Foley catheter drainage and seen by a clinical psychologist who unsuccessfully attempted hypnosis. Bladder retraining was started but it was 4 months before the patient was completely free of the catheter and, during this period, residual urines ran as high as 500 cc. She also had 1
234
ALLEN
FIG. 3. Case 3. A, cystogram and B, IVP in 12-year-old girl with lower abdominal cramps and urgency incontinence. C, IVP 1 year later after treatment.
episode with a fecal impaction manifested by a palpable lower abdominal mass. Ultimately, however, clear urine and residuals of less than 90 cc were achieved with bladder retraining, dantrolene sodium, stool softeners and sulfamethoxazoletrimethoprim. At the present time the residual urine is zero, the child's personality has changed (she is now more warm and outgoing) and a followup IVP shows considerable improvement in the status of the urinary tract (fig. 3, C). Case 4. C. D., a 12-year-old white boy, gave a long history of diurnal wetting and encopresis. He also admitted to abdominal cramps associated with a sensation of a need to void but stated that if he waited momentarily the pain would pass and he could resume playing. No one had ever advised him to do differently. The urinary tract problem finally surfaced when the patient began running a fever and was found to have infected urine. An IVP was normal except for excessive residual urine and a cystogram showed a large capacity smooth walled bladder with bilateral vesicoureteral reflux (fig. 4). Cystoscopy and neurological examination failed to uncover any subvesical obstruction or neurological disease. However, urodynamic studies showed that the child was unable to void on command; instead, he waited until bladder filling initiated an involuntary
detrusor contraction and then voided by relaxing the perinea! musculature. Since this occurred only intermittently and for momentary periods, urination was characterized by short bursts with high flow. Residual urine was 700 cc. The patient was started on bladder retraining and imipramine hydrochloride, and the wetting and fecal soiling ceased almost immediately. At the 3-month followup the residual urine was down to 220 cc and, although the child still tended to void in short explosive bursts, he was now able to initiate the stream upon command. At 5 months the residual urine was only 50 cc. The patient was then lost to followup momentarily but was located and seen again 4 months later, at which time it was discovered that he had run out of imipramine hydrochloride, that he was wetting himself again and that the residual urine had risen to 145 cc. Additional history revealed that he had entered junior high school where the first floor bathrooms were locked because of vandalism so that he had to go to the third floor to urinate. Since the child had only a few minutes between classes and since he had been advised that he would receive a detention if he were late to his next class, the voiding was necessarily rushed. lmipramine hydrochloride was resumed and the principal was contacted to enlist his cooperation with the problem.
235
NOJ:-I-h[EUROGENIC
Comment: ,ucwJ•-,;;u smooth on the cystogram, this was afflicted with the same problem as the other children in the series. Not all of these bladders have the characteristic Christmas tree appearance considered so typical of this disorder. This case also demonstrated the importance of close and in the management of these problems. CLINICAL MATERIAL
Within the last decade we have encountered 21 children with evidence of a severe obstructive uropathy in the absence of an anatomical or neurological explanation to account for it. All of these patients exhibited radiographic abnormalities of the urinary tract and all demonstrated failure to empty the bladder on multiple occasions. Clinical features. There were 13 and 8 girls ranging in age from 2 ½ to 12 years. Hm:vever, 7 these children, 2 ½ to 6 years old, were not recognized as having this problem when first seen and, in fact, the radiograms at the time of their initial visits were normal in 4. The most severe disease was seen in those children between 7 and 12 years old, while in 2 patients spontaneous resolution of the voiding abnormality occurred after puberty. The picture presented by these children thus has been that of an acquired disorder, first becoming manifest at some point after the potty training period, reaching its peak of destructiveness in late childhood and showing some tendency to resolution after
rnost aspect of the clinical has been vvetness, vvhich v,,ras seen in_ 19 of the 21 children and occurred diurnally as well as in most. In some this assumed the character of urge incontinence and was associated with detectable in the lower abdomen. In others it occurred more or less without apparent awareness on the part of the child. Some voided and others voided infrequently but most voided in an intermittent or interrupted manner. A sustained stream of good volume was unusual. For the most part it appeared that normal voiding patterns had never been established in these patients rather than that established voiding patterns had regressed. Many of these children also exhibited bowel dysfunction manifested by encopresis, chronic constipation with infrequent bulky stoois or even fecal impactions sufficient to produce a palpable mass in the lower abdomen. While information relative to bowel dysfunction was not always sought, the response was positive in 9 of the 13 patients in whom the question was raised. In 19 children the urine also was infected, although the infection in a clinical sense was seldom impressive. Few patients exhibited high fever or sepsis and often the clinical picture of infection was put together in retrospect after the urinary findings had come to light. The social history proved to be a particularly important part of the evaluation of these children since it often provided insight into factors of potential etiologic significance. For alcoholism was rampant in the family of 4 of those
FIG. 4. Case 4. Cystogram in 12-year-old boy with urgency incontinence and 700 cc residual urine
236
ALLEN
with severe voiding dysfunction, while divorces created signifi- recordert and intravesical pressure, flow rate and perinea] cant problems in several others. In 3 cases the father was noted muscle activity are measured simultaneously during the act of to be a dominant figure who verbally emasculated the child voiding. Repeated runs are made until reproducible results are with every word he spoke, while the mother remained passive obtained. to the point of being obsequious. Abnormalities in the perFrom these studies it has become quite apparent that sonalities of the children also were noticeable in many in- intravesical pressures are abnormally high in these children stances. Some were shy and withdrawn as though over- and that detrusor contractility is not only intact, it is hyperrewhelmed by the circumstances of their environment and others sponsive. The discoordination that exists between the detrusor were openly hostile. Several children demonstrated restless- and the sphincter has been clearly evident in the failure to ness and hyperactivity with short attention spans. This is not maintain pelvic relaxation during detrusor contraction as well to say that environmental or psychological factors could be as paradoxical contractions of the sphincter during efforts to identified in every case but they were striking in about half of void. The initial micturitional event in these children is usually them and undoubtedly could have been found in more had an a rise in intravesical pressure but despite a sustained elevation in this pressure, voiding itself occurs only upon relaxation of intensive search been made for them. Of the 21 patients 12 underwent 24 major operative proce- the pelvic floor and this is often unpredictable and of momendures at some point during the course of their disease. These tary duration. Thus, the flow tends to be intermittent and included 6 Y-V plasties of the bladder neck, 16 ureteral interrupted, and occasionally consists of short bursts of exploreimplantations (of which 5 failed) and 4 ilea! conduit urinary sive force. A rare patient has even been able to maintain a diversions, 1 of which was undiverted subsequently. There sustained stream without complete pelvic relaxation simply by were also 1 renal transplantation, 1 pyeloplasty, 1 ureteral re- developing an intravesical pressure so high as to overpower the section and 1 transureteroureterostomy. A critical analysis of sphincter. However, the pattern has been quite variable, even this group indicates that most of these procedures were either in the same patient (fig. 5), which further suggests that the unnecessary or ill-advised. discoordination is functional and not organic in origin. Objective features. Among the objective features of the Management. Because of our conviction that the non-neurodisorder the most consistent abnormality has been the appear- genic neurogenic bladder is a functional disorder in which there ance of the bladder. Typically, the bladder is of large capacity, is failure to coordinate the activities of 2 separate muscle heavily trabeculated and empties poorly. In only 2 cases did groups, we found it reasonable to believe that the disease could the bladder seem smooth walled on the cystogram and in both be overcome through a process of re-education or retraining. instances it was described as trabeculated at cystoscopy. In 2 When decompensation of the urinary tract has threatened the other patients the bladder, while heavily trabeculated, was of life of the patient catheter drainage has been used initially as a normal volume. Residual urine was documented in every case temporizing measure, otherwise the retraining program begins and in several patients the bladder was readily palpable at the time of the urodynamic evaluation of the child. In the suprapubically. Vesicoureteral reflux, usually bilateral, was presence of the parents repeated runs are made during which demonstrated in 12 patients but in 4 of them this finding was the child is encouraged to relax the perineum and maintain a not present on earlier available cystograms, suggesting that sustained stream without straining. By monitoring these events reflux in these cases may have been an acquired phenomenon the child can be directed in these efforts; indeed he can see the secondary to intravesical pressures, which were chronically results for himself on the recorder as he performs. This initial elevated. In several instances spontaneous disappearance of session sets the pattern for future practice sessions at home the reflux occurred when effective conservative treatment was and, upon discharge from the hospital, the patient is instructed instituted. to void every 3 hours or so while awake, to go to the bathroom Bilateral hydronephrosis was present in 14 patients and in 3 promptly whenever the sensation of a need to void arises and to others renal parenchymal scars were seen as a result of reflux set aside ample time for voiding so that the act is never rushed and infection. Thus, only 4 patients in the entire series had or performed under pressure. At the same time the child is innormal upper urinary tracts. However, of the 17 patients with structed to make sure that every effort is made to eliminate all upper urinary tract damage 5 had had normal x-rays initially of the urine from the bladder even if this requires multiple and it was only as the process unfolded that renal destruction voidings. Continued parental encouragement, rewards, perbegan to develop. Biochemical confirmation of renal damage sonal progress charts and so forth serve to remind the child of was available in most of those children with abnormal x-rays the goals desired. The children often are catheterized for reand in 5 cases renal functional impairment was severe. One sidual urine when they return for their followup visit, compatient required renal transplantation, 1 is currently on parisons are made with previous performance records and the hemodialysis and 3 others have advanced renal failure and are problem is discussed with the child and the family to uncover the explanation for any setbacks. Parental understanding and awaiting entry into the transplant program. Urodynamic features. The most definitive information rela- support are essential for success and, when indicated, profestive to the nature of the problem in these children has come sional psychological counseling for the family or child is sought. out, not from static studies, but from dynamic ones. Originally, Medication also has played an important role in the over-all we studied detrusor-sphincter coordination by placing elec- management of these patients, particularly imipramine hydrotromyographic electrodes in the anal sphincter of awake chloride, which has been quite effective in stopping wetness patients and reading the pattern of muscular activity directly and often fecal soiling as well. This response, by serving as an from the oscilloscope. Unfortunately, this is rather uncomfort- immediate indicator of improvement, also encourages the child able to the patient and requires a greater measure of coopera- to have confidence in the ultimate success of the treatment. tion than can be obtained easily in small children. Further- Bethanechol chloride has been helpful in lowering the residual more, it provides no permanent record of the event. More urine in a few instances when the bladder is badly decompenrecently, we have been inserting 2 No. SF silicone catheters* sated, and dantrolene sodium and phenoxybenzamine hydropercutaneously into the bladder during the cystoscopic proce- chloride have been used occasionally, although with doubtful dure, while at the same time, small insulated wires are benefits. Stool softeners and enemas have been required as passed through a 25 gauge needle, hooked into the anal adjunctive measures in a number of instances and various sphincter and taped into place. Later the same day or the tranquilizers have been used on occasion to combat hyperactivfollowing morning the child is connected to a 3-channel ity and anxiety. In no instance, however, have such medica* Cystocath, Dow Corning Corp., Midland, Michigan. t Life-Tech Instruments, Inc., Houston, Texas.
NON-I\JEUROGENIC NEURO{}E:NIC: BLADDER
237
PRESSURE
~ so 25
f'LOW
FIG. 5. Urodynamic study in 4-year-old boy with short attention span shows 2 events. The child concentrated upon his efforts to maintain a sustained stream and managed to keep sphincter suppressed quite well (left arrow). On the next run, however, he lost interest in study and failed to coordinate voiding efforts so that the stream was interrupted (right arrow).
tions been intended to supplant bladder retraining, which remains the cornerstone of the management protocol. Careful followup has been an essential part of the program. Six months of close observation are believed to be the minimum necessary to ensure that no relapse occurs and in most cases a year or more is required before habit patterns are well established. It is comforting to note, however, that every child treated by this protocol has shown gradual but steady improvement clini<;ally and radiographically, and several cases have been considered cured. DISCUSSION
The belief that urinary tract damage of the magnitude described herein could arise from functional factors alone has been difficult for many to accept and more often than not the disorder has been attributed to an isolated neurological defect, which involves the bladder alone and which cannot be detected by the usual peripheral neurological examination. In support of this several authors have described weak sphincters, 1 • 2• 7 while others have reported evidence for partial vesical denervation. 3 Yet these same authors acknowledge the existence of vesical spasticity in these patients, although the simultaneous presence of vesical denervation and vesical spasticity would be paradoxical since the phenomena tend to be mutually exclusive. In our experience these bladders have been hyperactive, not weak, developing voiding pressures as high as 175 cm. water and often exhibiting involuntary contractions of great force. If these features suggest subvesical obstruction then the failure to identify an anatomical abnormality in these patients is understandably disturbing but it should not be forgotten that obstruction may exist in other forms. The external urethral sphincter, for example, is not simply a passive structure in micturition; it exerts constant pressure against the urethra at all times, even at rest, and is truly silent only during urination. 8 Thus, effective voiding requires the active suppression of all sphincter tone. Without this kind of coordination urination may be impeded if not prevented altogether, as so often is the case in the paraplegic. Therefore, it is not unreasonable to believe that the non-neurogenic neurogenic bladder might be but another manifestation of detrusorsphincter discoordination. In fact, our studies support this contention.
But why should these children fail to master such a simple basic function as urination? Could it be that some organic lesion exists within the reticular formation of the brain stem 9 or in the muscle spindles of the external urethral sphincter 10 impairing the coordination between the sphincter and detrusor? Along a similar vein it should be noted that Campbell and associates 11 found a high percentage of organic indicators during the psychological testing of enuretics and Fermaglich 12 has reported finding abnormal electroencephalograms in such children. Of course we cannot exclude an organic lesion entirely but the natural history of the disease, its variable pattern and its response to conservative measures, such as bladder retraining and hypnosis, do seem to be more consistent with a functional disease than an organic one. As we have become more aware of dysfunctional voiding as a pathological entity, we cannot help but notice the wide spectrum of disorders encompassed by this concept. Besides embracing the non-neurogenic neurogenic bladder at one extreme and enuresis at the other, it includes little girls with recurrent infection, 13 lazy bladders, 14 supervoiders 15 and dysfunctional syndromes of other types. One which has surfaced in the course of this particular study has been that in which secondary vesicoureteral reflux overshadows the underlying bladder dysfunction to the point that it appears as the primary pathology. Repeatedly, we have encountered patients with reflux in whom reimplantation of the ureters has failed to control either the reflux or the infection and in whom a dysfunctional bladder is finally identified at the heart of the problem. Clearly, in any child with vesicoureteral reflux, a hard look at the bladder for trabeculation, residual urine, incontinence or other evidence of detrusor-sphincter dyssynergia is an essential part of the evaluation. This conviction that the non-neurogenic neurogenic bladder is a functional disorder rather than some obscure neuropathic one has the distinct advantage that it makes the disease treatable. No longer should it be necessary to condemn these children empirically to permanent diversion of the urine and a lifetime of artificial appliances. Hinman and Baumann 5 used hypnosis successfully in the management of these problems, we have used bladder retraining, and Mulholland and associates 16 performed unilateral pudenda! nerve section in order to weaken the external urethral sphincter. However, this last approach would not appeal to us because 1) it uses a destructive procedure to correct a functional problem and 2) even unilat-
238
ALLEN
eral pudendal neurectomy may have adverse effects upon potency in the male subject. 17 Nonetheless, the realization that conservative measures can be effective should offer new hope to a small segment of our population who might otherwise face a progressively downhill course to permanent disability or death. Drs. George Hurt, Elgin Ware, Richard Harrison, David Resiman, Melvin Gross, Joe Rappaport, W. T. Snodgrass and Ted Boone allowed inclusion of their patients in this study. REFERENCES
1. Dorfman, L. E., Bailey, J. and Smith, J. P.: Subclinical neurogenic bladder in children. J. Urol., 101: 48, 1969. 2. Martin, D. C., Datta, N. S. and Schweitz, B.: The occult neurological bladder. J. Urol., 105: 733, 1971. 3. Williams, D. I., Hirst, G. and Doyle, D.: The occult neuropathic bladder. J. Pediat. Surg., 9: 35, 1974. 4. Kamhi, B., Horowitz, M. I. and Kovetz, A.: Isolated neurogenic dysfunction of the bladder in children with urinary tract' infection. J. Urol., 106: 151, 1971. 5. Hinman, F. and Baumann, F. W.: Vesical and ureteral damage from voiding dysfunction in boys without neurologic or obstructive disease. J. Urol., 109: 727, 1973. 6. Hinman, F.: Urinary tract damage in children who wet. Pediatrics, 54: 143, 1974.
7. Emmett, J. L. and Simon, H. B.: Transurethral resection in infants and children for congenital obstruction of the vesical neck and myelodysplasia. J. Urol., 76: 595, 1956. 8. Scott, F. B., Quesada, E. M. and Cardus, D.: Studies on the dynamics of micturition: observations on healthy men. J. Urol., \,2: 455, 1964. 9. Vinson, R. K. and Diokno, A. C.: Uninhibited neurogenic bladder in adults. Urology, 7: 376, 1976. 10. Bradley, W. E., Scott, F. B. and Timm, G. W.: .:,phincter electromyography. Urol. Clin. N. Amer., 1: 69, 1974. 11. Campbell, W. A., III, Weissman, M. and Lupp, J.: Bender Gestalt test and the urodynamics of enuresis. J. Urol., 104: 934, 1970. 12. Fermaglich, J. L.: Electroencephalographic study of enuretics. Amer. J. Dis. Child., 118: 473, 1969. 13. Tanagho, E. A., Miller, E. R., Lyon, R. P. and Fisher, R.: Spastic striated external sphincter and urinary tract infection in girls. Brit. J. Urol., 43: 69, 1972. 14. DeLuca, F. G., Swenson, 0., Fisher, J. H. and Loutfi, A.H.: The dysfunctional "lazy" bladder syndrome in children. Arch. Dis. Child., 37: 117, 1962. 15. Gleason, D. M., Bottaccini, M. R., Reilly, R. J. and Byrne, J.C.: The residual stream energy is a diagnostic index of male urinary outflow obstruction. Invest. Urol., 10: 72, 1972. 16. Mulholland, S. G., Yalla, S. V., Raezer, D. M. and Duckett, J. W., Jr.: Primary external urethral sphincter hyperkinesia in a boy. Urology, 4: 577, 1974. 17. Comarr, A. E.: Personal communication, 1976.