0022-534 7/92/1485-1699$03.00/0 Vol. 148, 1699-1702, November 1992 Printed in U.S.A.

THE JOURNAL OF UROLOGY

Copyright© 1992 by AMERICAN UROLOGICAL ASSOCIATION, INC.

Voiding Dysfunction HISTORICAL CLUES TO THE COMPLEX OF DYSFUNCTIONAL VOIDING, URINARY TRACT INFECTION AND VESICOURETERAL REFLUX JAN D.

VAN

GOOL, KELM HJALMAS, TYTTI TAMMINEN-MOBIUS AND HERMANN OLBING ON BEHALF OF THE INTERNATIONAL REFLUX STUDY IN CHILDREN

ABSTRACT

The prevalence of nonneuropathic bladder/sphincter dysfunction was assessed with a questionnaire in 310 of the 386 children enrolled in the European branch of the International Reflux Study in Children. Despite the exclusion criteria (neuropathic bladder, anatomical malformations other than vesicoureteral reflux and overt dysfunctional voiding or urge incontinence), the prevalence of bladder/sphincter dysfunction was as high as 18%. Four patterns of dysfunction emerged: urge syndrome, staccato voiding, fractionated and incomplete voiding, and voiding postponement. The questionnaire proved helpful in detecting low profile cases of bladder/sphincter dysfunction, as well as indicating the need for further urodynamic studies. A strong correlation was established between recurrences of urinary tract infections, as well as disappearance of vesicoureteral reflux (negative correlation) and nonneuropathic bladder/sphincter dysfunction. This finding implies that detection and treatment of bladder/sphincter dysfunction are essential in every child with the complex of recurrent urinary tract infection and vesicoureteral reflux. The patients enrolled in the International Reflux Study in Children (IRSC) represent a unique cohort with vesicoureteral reflux and urinary tract infections. Diagnosis and treatment of urinary tract infection were standardized for the 8 participating centers according to strict criteria; followup was at prescheduled intervals to detect any recurrence and a treatment protocol was followed for low dose chemoprophylaxis, antibiotic treatment and instructions on voiding habits. 1 Patients were referred to the study with a primary diagnosis of dilating vesicoureteral reflux and (recurrent) urinary tract infection, and great care was taken to exclude those with overt or occult neuropathic bladder, or with anatomical malformations of the urogenital tract other than reflux. Symptoms of severe dysfunctional voiding and urge incontinence also constituted exclusion criteria.1 Because of the apparent relationship between bladder/ sphincter dysfunction and the complex of vesicoureteral reflux Participating hospitals and principal investigators: University Children's Hospital, Bonn, Germany: Rudolf Mallmann. University Children's Hospital, Universite Libre de Bruxelles, Belgium: Michelle Hall, University Children's Hospital, Essen, Germany (Coordinating Center): Hermann Olbing (Chairman), Tytti Tamminen-Miibius (Coordinator) and Wolfgang Rascher. University Children's Hospital, Gothenburg, Sweden: Kelm Hjiilmas and Ulf Jodal. Department of Urology, University of Hamburg, Germany: Rainer Busch. University Children's Hospital, Helsinki, Finland: Olli Koskimies, University Children's Hospital, Oulu, Finland: Juhani Seppanen. Karolinska Institutet, St. Goran's and Sachska Children's Hospitals, Stockholm, Sweden: Anita Aperia. Data processing and statistical analysis: Institute for Medical Data Processing and Biomathemathics, University Essen, Germany: Hildegard Lax-GroE. and Herbert Hirche. Scientific advisors: Klaus-Dieter Ebel (pediatric radiology), Jan van Goo! (pediatric urodynamics), Kalle V. Parkkulainen (pediatric surgery), Jean M. Smellie (pediatrics) and Jan Winberg (pediatrics). Supported by the VW-Foundation (Grants AZ 35 807, AZ I/37 504) until 1985 and thereafter by the Bundesministerium fiir Forschung und Technologie (Grant 07068343).

and urinary tract infection, 2' 3 it was decided to use a finer filter for the detection of bladder/sphincter dysfunction than just the presence or absence of overt dysfunctional voiding or urge incontinence. To this end, a questionnaire was developed to differentiate between manifestations of the urge syndrome and all other forms of daytime and nighttime wetting. From 1985 on the questionnaire was used on an annual prospective basis in all children admitted to the European branch of the IRSC. This report is based on the first 2 questionnaires sent to the whole cohort of 401 patients recruited in Europe. MATERIALS AND METHODS

Between 1985 and 1986, 401 first questionnaires were mailed to the 8 participating centers of the European branch of the IRSC to be completed by trained observers (pediatricians, pediatric urologists, urotherapists) in direct interviews with the parents and the children. The questionnaire is delineated in the Appendix; it was validated in a pilot study on urge syndrome and recurrent urinary tract infection in a group of children with persistent daytime wetting. 4 Questions are arranged in groups: nighttime wetting, daytime wetting, urge and reactions on urge, and micturition. Great care was taken to ensure that the questionnaires were completed by trained personnel, not by the parents, in the absence of urinary tract infection. Of the 8 participating centers 3 did not respond to the first questionnaire, and could not participate further with this item of the IRSC; the distribution of their 45 patients according to sex and age did not differ significantly from the main population of the study, which consisted of 386 children (15 of the 401 recruited patients changed treatment after allocation and are not counted). The remaining 5 participating centers enrolled 326 patients, and completed the first and second questionnaires mailed in 1986 and 1987 on 310 patients for a response rate of 95%. This rate brought the total number of

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children with missing questionnaires to 76 (45 missing, 15 treatment changes, 16 nonresponders). The distribution of the 310 patients with completed questionnaires in the 3 groups of the IRSC (surgical treatment, medical treatment and sideline) did not differ significantly from the 76 children with missing questionnaires. For the sake of completeness and comparison, the data on urinary tract infection and vesicoureteral reflux have been tabulated for the children with missing question naires as well as for those with completed questionnaires. The completed questionnaires were tallied and interpreted blindly by 2 experienced pediatric nephrologists. Classification was done on the data of 2 questionnaires per patient 1 year apart to ensure consistency in the scores. Of the 62 questionnaires that scored positive 7 concerned primary nocturnal enuresis only. The remaining 55 were considered positive or -h-ighly-suggestiv~~--dysfuncti-0nal-¥oiding---0-I'-Ur-ge-sy-ndrome, and they were subdivided into 5 different categories: urge syndrome with or without urge incontinence, staccato or dyssynergic voiding, fractionated and incomplete voiding with a tendency to lazy bladder syndrome,5 voiding postponement and nonclassifiable. Definitions and terminology for bladder/ sphincter dysfunction conform to the standards recommended by the International Continence Society except when specifically noted. The data on recurrent urinary tract infection in the 386 IRSC patients were used to compare incidence and prevalence of urinary tract infection in the 55 children who scored positive for bladder/sphincter dysfunction, in the 255 children who scored negative or had isolated nocturnal enuresis, as well as in the 67 children with missing questionnaires. For comparison, the chi-square test was used. The data are represented separately for each of the 3 groups of the study to rule out significant differences in distribution. IRSC data on vesicoureteral reflux of the children in the medically treated sideline groups were also cross-tabulated against the presence or absence of bladder/sphincter dysfunction according to the questionnaire, as well as against missing questionnaires. These data are presented per patient, for the first 5-year followup. The IRSC reports on 3 categories of change in grade of vesicoureteral reflux, apart from cessation or persistence of reflux: 1) variability of reflux was defined as any change in grade (including occasional negative findings) without a clear tendency to cessation at the end of followup; 2) diminishment of reflux was defined as a steady lowering of the grade without complete final resolution and 3) intermittent reflux was defined as occasional reappearance after negative findings, with final resolution. In children with bilateral reflux variability in grade was given priority above diminished or intermittent vesicoureteral reflux in the contralateral renal unit, intermittent reflux was given priority over contralateral diminishment and persistence had priority over any change in the contralateral renal unit. RESULTS

Dysfunctional voiding and urge syndrome. Despite the fact that overt symptoms of dysfunctional voiding and urge syndrome constituted an exclusion criterion, the prevalence of persistent bladder/sphincter dysfunction, as detected with the questionnaire, was as high as 18%: 55 of 310 children scored positive, 7 had isolated nocturnal enuresis (with normal bladder/sphincter function) and 248 scored negative. The overall prevalence of bladder/sphincter dysfunction did not change significantly with the randomly allocated treatment modality for vesicoureteral reflux: in the group with surgical treatment 86% had normal bladder/sphincter function versus 82% in the group with medical treatment; in the sideline group 76% had normal bladder/sphincter function. Four distinctly different types of bladder/sphincter dysfunction6 emerge from the data in the questionnaires (table

TABLE

1. Four types of bladder/sphincter dysfunction in 310 study

children No.(%) Normal bladder/sphincter function Urge syndrome Staccato voiding Fractionated and incomplete voiding Voiding postponement Unclassifiable Total

255 (82) 26 (8) 4 (1)

14 3

(5) (1)

8

(3)

310 (100)

1). 1) Urge syndrome, with or without urge incontinence, was present in 26 children. Urge syndrome was characterized by frequent attacks of imperative urge to void countered by hold maneuvers, such as squatting. Urge incontinence, when present,-mm-ally-peak-ea in--the---af-ternoen----and--e-0nsisted---0-f-sl-ig-ht urine loss only. Symptoms and signs are caused by uninhibitable contractions of an overactive detrusor muscle early in the filling phase; these contractions generate high pressures while counteracted by the 'emergency brake' of voluntary pelvic floor contraction. The small for age functional bladder capacity results in a high voiding frequency but micturition itself is usually normal with complete relaxation of the pelvic floor. 2) Staccato voiding (often termed dyssynergic voiding,7 analogous to neuropathic bladder dysfunction) occurred in 4 children. In 2 children staccato voiding was combined with urge syndrome. It is caused by bursts of pelvic floor activity during voiding; peaks in bladder pressure coincide with dips in flow rate, the flow time is prolonged and bladder emptying is often incomplete. 3) Fractionated and incomplete voiding was found in 14 children. Voiding frequency was low and micturition occurred in several small fractions with abdominal pressure as the driving force. The detrusor muscle is hypoactive, urge is inhibited easily (when felt at all) and the functional bladder capacity is large for age. Bladder emptying will be incomplete with significant residual volumes. Extreme cases may end up as lazy bladder syndrome with fractionated and incomplete voiding secondary to detrusor decompensation. 4) Voiding postponement, a peculiar pattern, was noted in 3 children also with a low voiding frequency but without fractionated voiding. In characteristic situations (at playgrounds) these children postpone micturition as long as possible until urge is so imperative that voiding occurs irrevocably, usually in the pants. In 8 children no definite pattern could be reconstructed from the questionnaires. One child had what could be termed a transitional phase between urge syndrome and fractionated voiding, while the other 7 experienced urge several times before each micturition but could cope with minimal use of hold maneuvers. In these 7 children urodynamics might reveal detrusor overactivity at the end of an otherwise normal filling phase with normal values for functional bladder capacity. Urinary tract infections. When the data on the prevalence of urinary tract infection in the 310 study children were stratified according to normal or abnormal bladder/sphincter function and missing questionnaires, separately for each of the 3 main groups in the study, it could be seen that the recurrence rate of urinary tract infection was the same for IRSC patients treated surgically as for those in the medical treatment and sideline groups (table 2). In all 3 groups almost 30% of the children experienced at least 1 episode of symptomatic urinary tract infection during-the followup of 5 years. The groups differ in only 1 aspect: in the surgical group low dose chemoprophylaxis was discontinued after antireflux surgery, while the medical and sideline groups remained on chemoprophylaxis for the whole duration of the study. In table 2 the data on urinary tract infection in the 76 children without completed questionnaires are tabulated separately: because of the high incidence (30%) of inconclusive urine cultures no conclusions can be made for this group. In

TABLE 2. Chiidren with recurrences of

in/ectio1l versus bladder/sphincter function (questionnaire) in surgica( rrwdrcal and sideline groups Surgical

None Normal questionnaire Abnorm,;l questionnaire Subtotals Missing questionnaire Totals

Bacteriuria

69

Medical Symptomatic Urinary Tract Infection

None

29 7

70 11

9

36

81

10

11

80

10

Sideline Symptomatic Urinary Tract Infection

None

Bacteriuria

1

23 11

31* 8

10

34

39

Bacteriuria

12t

6

7

15t

3

12

92

16

43

96

17t

13

46

56

Symptomatic Urinary Tract Infection

Totals

3

11 6

3

17

3

21

255 55 310 76 386

4

* Including 1 patient with dubious urine culture. t Including 30% dubious urine cultures.

Three different modes of progression of reflux nephropathy were analyzed in a stepwise logistic regression procedure for correlation with the presence or absence of bladder/sphincter dysfunction: 1) appearance of new scars, 2) progression of old scars and 3) progression of areas of cortical thinning to scars. No correlation could be established for any form of progression of reflux nephropathy during the first 5 years of followup.

Children with recurrences of symptomatic urinary tract infections and asymptomatic bacteriuria versus bladder/sphincter function (questionnaire)

TABLE 3.

No. Children(%) Bladder/Sphincter Function Normal Abnormal Totals

None

Bacteriuria

170 (66.7) 30 (54.5) 200 (64.5)

22 (8.6) 1 (1.8)

23 (7.4)

Totals

Urinary Tract Infection 63 (24.7) 24 (43.6) 87 (28.1)

255 (100) 55 (100) 310 (100)

DISCUSSION

Chi-square= 5.6, degrees of freedom= 2, p