1. Enuresis Stephen Confer, MD Ben O. Donovan, MD Brad Kropp, MD Dominic Frimberger, MD University of Oklahoma Department of Urology Section of Pediatric Urology

2. Enuresis Involuntary discharge of urine Nocturnal enuresis - nighttime wetting Diurnal enuresis - daytime wetting 15% normal children have nocturnal enuresis at 5 years of age 99% are dry by age 15 Nocturnal enuresis is 50% more common in boys More girls dry day and night by age 2

3. Enuresis 80% enuretics are wet only at night –most are primary enuretics - never been dry 25% are secondary enuretics –initially dry at night by age 12 –relapse for 2.5 years –may be associated with emotional stress Only 10% who develop daytime dryness relapse –wet for 1.2 years

4. Rule of 15’s

5. Development of Urinary Control Infant –spontaneous micturation as a spinal cord reflex –distention simulates a detrusor contraction –voluntary sphincter is integrated into the reflex constricts to prevent incontinence relaxation during micturation low pressure voinding –As bladder capacity increases and fluid intake decreases, number of voidings decrease

6. Development of Urinary Control Development of adult type control –Capacity of the bladder must increase –Voluntary control over the striated sphincter usually complete by 3 years –Direct volitional control over the spinal micturition reflex to initiate or inhibit bladder contraction Complete by age 4

7. Development of Urinary Control Order of Control –Control of bowel at night –Control of bowel during the day –Control of bladder during the day –Control of bladder at night

8. Etiology Nocturnal enuretics –normal psychologically and physiologically –fail to awaken when bladder is full or contracts –unknown etiology

9. Etiology Urodynamic Factors –Reduced bladder capacity by 50% anticholinergics increase capacity by 25 - 60% –Bladder instability seen in many with day and night enuresis in children with daytime symptoms of frequency/urgency anticholinergics are helpful –Those with nocturnal enuresis do not have a higher incidence of daytime instability nighttime contraction is just as likely to wake the child as to cause wetting anticholinergics not effective

10. Etiology Sleep Factors –Theory that sleep disturbance causing the child to sleep too deeply or fail to awaken –Enuretics do not sleep more soundly than controls –Enuresis occurs in deep sleep and in REM sleep –Enuresis may be a developmental delay perception and inhibition of bladder filling and contraction by the CNS

11. Etiology Sleep Factors - Types of Enuresis –Type I Stable bladder with EEG response during enuresis –Type IIa Stable bladder with no EEG response during enuresis 80% change to I –Type IIb Unstable bladder with no EEG response during enuresis 20% change to IIa 60% change to I

12. Etiology Alteration in Vasopressin Secretion and Nocturnal Polyuria –High ADH as night leads to less urine production –Enuretics have stable ADH during the day and night larger amounts of dilute urine at night may be delayed development of the ADH circadian rhythm –ADH levels increase normally with bladder fullness Bladder emptying may cause decreased nighttime ADH levels in enuretics

13. Etiology Developmental Delay –Altered urodynamic function, sleep and ADH secretion occur normally in infants and young children –Nocturnal enuresis may be an arrest in development –Each physiologic alteration tends to resolve spontaneously –Neurologic disease is rare with monosymptomatic nocturnal enuresis

14. Etiology Developmental Delay –Stress has been shown to delay development of urinary control enuresis is 3 times higher when associated with stressful circumstances –Associated with encopresis 10 - 25% delay in development is not isolated to urinary control

15. Etiology Genetic Factors –33% fathers –20% mothers –One parent enuretic - 44% –When mother and father were enuretics, 77% children affected –15% enuresis in children of nonenuretics

16. Etiology Organic Urinary Tract Disease –Enuretics are predisposed to UTIs especially girls many have diurnal symptoms due to bladder instability –Most with monosymptomatic nocturnal enuresis do not have an organic cause <10% meatal stenosis is not a cause - meatotomy does not cure –Increased incidence of organic abnormalities with diurnal symptoms These may need U/S to exclude obstruction - esp. boys controversial

17. Evaluation Families with a history of enuresis await spontaneous cure - more tolerant Families without such a history can place great pressure on the physician to perform tests and produce a cure Urologic tests are rarely indicated for monosymptomatic bedwetters –Rarely find an organic lesion

18. Evaluation Negative Screening Evaluation for Enuresis –Prepubertal age –Lifelong enuresis –Nocturnal enuresis only –No daytime wetting, urgency, polyuria –No UTI –Negative UA and Culture –Normal PE - including neurologic exam

19. Evaluation Screening creates 3 groups –Children with nocturnal enuresis no further evaluation –Children with UTI or neuropathy full urologic workup –Children without UTI or neuropathy with day and night enuresis or dysfunctional voiding U/S to exclude anatomic abnormality Assesses hydro, bladder wall thickening, emptying

20. Evaluation Screening creates 3 groups –Normal U/S pharmacologic therapy is symptoms are not severe If dysfunction persists or is severe - Urodynamics to exclude neuropathy and guide further treatment

21. Treatment Treatment is discouraged before age 7 –less successful –age when bedwetting interferes with social activities

22. Treatment - Drug Therapy Anticholinergics –Only 5 - 40% effective (equal to placebo) in nocturnal enuretics –useful to eliminate bladder instability urgency, frequency, day and night incontinence (87%) more effective in urodynamically proven instability (90%)

23. Treatment - Drug Therapy Reduction of Urinary Output –limiting fluids in the day is not effective –DDAVP - intranasal or oral significantly reduces number of wet nights only 25% dry for 14 or more consecutive days temporary treatment - only 33% cured may lead to hyponatremic seizures - limit fluids before administering dose not first-line treatment

24. Treatment - Drug Therapy Imipramine –Cure > 50%Improvement - 80% –Discontinuation - 60% relapse –Peripheral action weak anticholinergic weak smooth muscle antispasmotic –Central action antidepressant activity not involved decreases REM early sleep - less enuresis early in the night and more common in the last third of sleep –does not lead to more awakenings at night –effect on sleep is independent of its effect on enuresis

25. Treatment - Drug Therapy Imipramine –Recommended dosage 25 mg age 5-850 mg for older children results in optimal plasma levels in only 30% increased dosage not justified –toxicity –25% are nonresponders despite higher doses –2 week trial adjust dosage and timing of administration –Long-term effects not known in children weaning the drug reduces relapses

26. Treatment - Behavior Modification When used in a motivated family, result in most effective rate of sustained cure 1st line therapy in these patients

27. Treatment - Behavior Modification Bladder Training –goal is to increase the time interval between voiding –enlarges functional capacity of bladder –Child is encouraged to retain urine after 1st urge –When combined with conditioning therapy, very successful

28. Treatment - Behavior Modification Responsibility Reinforcement –motivation child assumes responsibility for wet and credit for dry –reward with progressively longer dry intervals –response shaping as a consequence of rewards for behavioral changes –reinforcment –Part of a multicomponent behavioral program

29. Treatment - Behavior Modification Conditioning Therapy –Use of a urinary alarm is the most effective for nocturnal enuresis - 80% cure child wakes up and voids in toilet followed by sensation of a full bladder and production of the same inhibition as the alarm failure is often due to lack of parental understanding and cooperation may take months

30. Treatment - Behavior Modification Conditioning Therapy –Once enuresis is cured (2 weeks dry) relapse is reduced by overlearning techniques forcing fluids prior to bed - bladder overdistention provides a stronger conditioning stimulus reinforced by alarm sounding intermittently some nights but not others –May be combined with pharmacotherapy

31. Adult Enuresis Occurs in 2 cases –Persistent primary enuresis - 1% of the population More have urodynamic abnormalities (30 - 70%) Not due to anatomic abnormality - same as in children Treatment similar to that of children –Secondary adult onset enuresis Requires anatomic investigation, neurologic evaluation and urodynamics Occurs with obstructive sleep apnea –increased atrial natriuretic peptide and activation of renin- angiotensin system

32. Summary Exclude- infection, neuropathy, obstruction Reassurance- harmless, perhaps genetic, high rate of spontaneous resolution Recognize- not all parents and children are ready for therapy Begin with conditioning therapy and behavior modification Add the use of medications as necessary