1. Enuresis Ali Derakhshan MD Shiraz University of Medical Sciences, Shiraz-Iran

2. ENURESIS: SOME GENERAL POINTS DEF: Wetting twice a week for 3 consecutive months Chronological age: 5-6 years The disorder : either primary or secondary The disorder : either primary or secondary Primary enuresis 85% Secondary enuresis dryness for at least 6 months then resumed wetting 15% Nocturnal only, diurnal only, nocturnal &diurnal Prevalence different in diff. countries

3. Epidemiology of Enuresis 15 to 20 % of children night time wetting at five years of age The spontaneous resolution rate is15%/yr At 8 yr 7% of children At age 15 only 1 % Boys wet the bed twice > than girls till 11 yr then equal. EN more common 1 st child, low socioec.., disease 1 st 4 yr,large size family Daytime control is typically accomplished by the age of 3 or 4. Daytime control is typically accomplished by the age of 3 or 4. Nighttime dryness expected by 6yrs Of children with En 22%day,17%day and night and 61%night 1 ST bowel control at night, then day, then day time urine control then night… Rule of 15’s

4. Factors That May Contribute To EnuresisEnuresis Genetic factors Family history of enuresis Delayed maturation A stressful life event, such as the birth of a sibling, Delayed arousal from sleep Malfunction of detrusor muscle Chronic constipation can irritate the bladder and ↓functional volumeconstipation Sleep apneaSleep apnea (periods of non-breathing during sleep) Urinary tract infection High urine production during the night

5. Enuresis: Genetic Bases Genetic: higher incidence of enuresis in children whose parents were enureticGenetic: higher incidence of enuresis in children whose parents were enuretic In families where both parents have a history of enuresis, 77 % of children will have enuresis.In families where both parents have a history of enuresis, 77 % of children will have enuresis. when one parent has had enuresis, 44 % of children will be affected; when one parent has had enuresis, 44 % of children will be affected; Homozygote twins 68%,Hetrozygote …36%Homozygote twins 68%,Hetrozygote …36% 74% of boys with EN,58% girl one or both parents74% of boys with EN,58% girl one or both parents In only 15 % of children family history is negativeIn only 15 % of children family history is negative nocturnal enuresis was associated with 2 markers, 13q13 & 13q14.2, on long arm of chromosome 13nocturnal enuresis was associated with 2 markers, 13q13 & 13q14.2, on long arm of chromosome 13 An autosomal dominant pattern has been reportedAn autosomal dominant pattern has been reported

6. Enuresis and Upper Airway Obstruction Nocturnal enuresis association with upper airway obstruction In these instances, surgical relief of the obstruction by tonsillectomy, adenoidectomy or both has been reported to diminish nocturnal enuresis in up to 76 percent of patients.

7. Enuresis and Anatomic Factors In Isolated primary enuresis, usually no anatomic abnormalities

8. ADH secretion Normal children have a diurnal rhythm of plasma vasopressin and urinary output with a nocturnal increase in decrease in urinary excretion rate, and increase in urine osmolarity  Normal children have a diurnal rhythm of plasma vasopressin and urinary output with a nocturnal increase in ADH decrease in urinary excretion rate, and increase in urine osmolarity  Enuretics have an abnormal rhythm of plasma vasopressin and urinary output with nocturnal low vasopressin, large urinary excretion rate, and lower urinary osmolarity  The relationship between ADH secretion and nighttime urinary flow rates remains controversial.  abnormalities in ADH secretion appear to play a role in at least some patients with nocturnal enuresis.

9. OTHER POSSIBLE ETIOLOGICAL FACTORS: BEHAVIORAL FACTORS Enuresis psychological problems psychological problem 2 nd enuresis Behavioral regression due to stress (divorce, abuse, school trauma, hospitalization) does seem to be involved in many cases of secondary enuresis.

10. ORGANIC CAUSES UTIDMDICRF

11. Secondary Nocturnal Enuresis Psychological factors: stress, anxiety, depression Neurogenic detrusor underactivity and overflow incontinence Dysfunctional voiding Urinary tract infection Bladder outlet obstruction DM,DI,CRF

12. Diurnal enuresis Detrusor instability is commonly found Urgency frequency and urge incontinence Pelvic floor spasticity and dysfunctional voiding May be associated with constipation or fecal incontinence

13. UTI AND ENURESIS IN 15% of children with UTI EN is 1 st symptomIN 15% of children with UTI EN is 1 st symptom EN is common in children with asymptomatic bacteriuriaEN is common in children with asymptomatic bacteriuria UTI more common in EN childrenUTI more common in EN children Treatment of UTI improved EN in 30%Treatment of UTI improved EN in 30% Girls with diurnal and nocturnal EN 50% chance of UTIGirls with diurnal and nocturnal EN 50% chance of UTI

14. EVALUATION History Physical examination INVESTIGATIONS

15. CLINICAL AND PARACLINICAL EVALUATION HISTORY: birth Hx, developmental milestones, previous control, social setting, inside toilet, voiding pattern, wetting episodes, bowel control, fecal soiling, incontinence, UTI, primary or secondary? Drinking habits Family History Previous treatment, Motivation for Rx Previous treatment, Motivation for Rx Complete PE: child development Complete PE: child development

16. INVESTIGATIONS 1-Primary EN: Urinalysis/ specific gravity, Ca/Cr,U/C if indicated -Imaging studies not indicated 2-2 nd Enuresis more investigations -U/A, U/C, BUN, Cr, if UTI US and VCUG and….. 3-incontinence, abnormal neurological signs: US,VCUG and Urodynamic study

17. TREATMENT OF NE -treatment of organic conditions if any   General measures - Restrict fluid 3-4 hours before bedtime -Empty bladder before sleep -Salt restriction - Encourage child to make bedtime resolution - Keep a chart of wet and dry nights - Reward for dry nights -Avoid punishment & criticism

18. TREATMENT OF NE Non-pharmacological - Reassurance and counselling - Bladder training programme - Enuresis alarm Pharmacological -Desmopressin -Oxybutynin - Imipramine

19. Pharmacological treatment Bell and Pad>7 yr 70-90% response,10%recurrence Bell and Pad>7 yr 70-90% response,10%recurrence Imipramine- rarely used now in children Used in children over 6- can TX for 3-6 mo effective in 50-60% (author 24%), 25%remain dry 60%relapse Side effects-, toxicity, sleep and appetite dry mouth Desmopressin - DDAVP Synthetic analog of antidiuretic hormone vasopressin Spray and Tablet forms* Rapid response 40-70% response but 50%- 90% relapse Side effects- HA, convulsion due to water intoxication   Oxybutynine + imipramine or Oxybutynine + Desmopressin  Alarm Rx+  Alarm Rx+ Desmopressin  Imipramine and desmopressin may be combined *Black box warning

20. Evidence Based Medicine Enuresis alarms are the most effective treatment for primary nocturnal enuresis with lasting effects. Drug treatment can be useful for short term relief of symptoms but consider potential adverse effects

21. Conclusions Nocturnal enuresis is multifactorial A 15% annual spontaneous cure rate Treatment should match to etiologies Balance between bladder functional capacity and nocturnal urine output appear to be the most important

22. The End THE END