1. Nocturnal enuresis By
Dr. Turky Al-Mouhissen
R4 Urology

2. Outline: Introduction & definition Epidemiology & natural history
Physiology of bladder maturation
Causes
Evaluation
Management

3. Introduction & definition
Enuresis defined as involuntary voiding
When it occurs at night it is termed nocturnal enuresis
daytime incontinence is termed diurnal enuresis
1ry : who never achieved peroid of dryness at night time
2ndry: who achieved period of dryness

4. At 5 yrs of age, 15 % of children remain incompletely continent of urine
Most of these children have isolated nocturnal enuresis ( monosymptomatic enuresis )
Monosymptomatic enuresis divided into 1ry & 2ndry

5. 1ry enuresis: who never achieved a satisfactory period of nighttime dryness
80 % of nocturnal Enuresis
2ndry enuresis: who had a period of dryness, usually for at least 6 mo. before the onset of wetting begins
20 % of noc. Enuresis
Often associated with unusually stressful event

6. 20 % of children who have nocturnal enuresis also have daytime symptoms
Daytime symptoms may be limited to urgency and frequency, but often include incontinence (diurnal enuresis)
Urologic and neurologic disorders (eg, detrusor instability, recurrent UTI, spinal dysraphism) more common among children with diurnal symptoms

7. Nocturnal enuresis + daytime symptoms =
complex or complicated enuresis ( dysfunctional voiding ) [
Noc. Enuresis + Urinary & bowel symptoms =
dysfunctional elimination syndrome

8. EPIDEMIOLOGY AND NATURAL HISTORY

9. 5 years: 16 %
6 years: 13 %
7 years: 10 %
8 years: 7 %
10 years: 5 %
12 to 14 years: %
15 years: %

10. Boys = twice girls
resolves spontaneously at a rate of 15 % / year
The longer the enuresis persists, the lower the probability that it will spontaneously resolve

11. In a study by the college of medicine in Dammam, saudi arabia
cross-sectional population-based study
Data were collected using a self-administered questionnaire
644 school children aged 6-16 years were selected randomly
Enuresis prevalence was
16.3% among boys and 13.8% among girls
The overall prevalence was 15%
The 83 children who had enuresis during sleep, 25 (30.1%) wet their beds during day time sleep
: Acta Paediatr Oct;85(10): Links
Enuresis: prevalence and associated factors among primary school children in Saudi Arabia
Kalo BB, Bella H.

12. Bladder maturation
Normal bladder function entails a complex interrelation btwn autonomic and somatic nerves
They are integrated at various sites in spinal cord, brain stem, midbrain, and higher cortical centers
The complex coordination permits urine storage at low pressure with high outlet resistance and voiding with low outlet resistance and sustained detrusor contraction

13. Central organization of mic. Reflex by centers in
cerebrum, posterior hypothalamus, midbrain, pontine, sacral spinal cord
Parasymp. Supply by pelvic nerve arising from S 2-4, to the detrusor muscle
Symp. Supply by hypogastric n. from t innervating bladder neck & urthral smooth m.
Somatic supply. By pudendal n. innervating ext. urethral sphinter

14. At birth, bladder function is coordinated through the lower spinal cord and/or primitive brain centers
Voiding at this stage is efficient but uncontrolled: uninhibited contraction is caused by progressive and sustained bladder filling
Voiding in the newborn also may be initiated by neurologically stimulating activities such as feeding, bathing, tickling, etc.

15. The newborn voids approx. 20 times per day
During the first 3 yrs, bladder capacity increases disproportionately relative to body surface area
At 3 yrs, No. of voids per day decreases to approximately 11, while mean voided volume increases nearly fourfold
At 4 years, most children void 5-6 times/day

16. Development of bladder control appears to follow a progressive maturation
child first becomes aware of bladder filling
subsequently develops the ability to suppress detrusor contractions voluntarily
finally learns to coordinate sphincter and detrusor function
These skills usually are achieved, at least during the day, by 4 yrs of age.

17. Nighttime bladder control is achieved months to years after daytime control, but is not expected until 5 – 7 yrs of age
Incomplete development of bladder control results in more complex wetting problems that almost always associated with diurnal enuresis
uninhibited bladder of childhood
bladder sphincter dyssynergy
recurrent UTI
some cases of vesicoureteral reflux

18. Causes: Maturational delay Genetics Functional small bladder capacity
Abnormal diurnal secretion of vasopressin (antidiuretic hormone, ADH)
Nocturnal polyuria
Detrusor instability
Sleep disorders
Psychological issues

19. Maturational delay
In almost all cases, monosymptomatic nocturnal enuresis resolves spontaneously
This suggests that delayed maturation of a normal developmental process plays a role
Some studies have demonstrated increased incidence of delayed language & gross motor development and slowed motor performance among children with enuresis

20. Genetics
Monozygotic twins twice that among dizygotic twins (68 versus 36 %)
One parent have h/o prolonged nighttime wetting, ½ of the offspring are affected
Both parents affected, ¾ the offspring are affected
When neither parent has a history of nocturnal enuresis, only 15 % of offspring are affected
An autosomal dominant form was identified in Danish families and linked to a locus on chr. 13q13-q14.3
Additional genetic loci for enuresis have been identified on chr. 12q and 22q11 [

21. Small bladder capacity
At birth, bladder volume approx. 60 mL
it increases with age at a relatively steady rate of approximately 30 mL per year
Children with noc. enuresis, even who do not have daytime symptoms, have noted to have smaller bladder capacity than age-matched children who do not have nocturnal enuresis

22. In a study showed, the reduced bladder capacity appears to be functional rather than anatomical
In another study, the maximal bladder capacity during the daytime was similar between children with enuresis and controls
However, among children with enuresis, the maximal voided vol. during night was significantly smaller than the maximal daytime bladder capacity

23. Nocturnal polyuria and ADH
It has been suggested that increased nighttime U.O.P may play a role in nocturnal enuresis
In children who don`t have enuresis, U.O.P. during the night bcs the secretion of ADH and other regulatory hormones follows a circadian pattern, with increased secretion at night

24. studies have indicated that nocturnal enuresis children have decreased nocturnal secretion of ADH increased U.O.P.
One of the reasons may be small bladder capacity, since ADH secretion is thought to increase with bladder distension
The relationship between ADH secretion and nighttime urinary flow rates remains controversial

25. Abnormalities in ADH secretion appear to play a role in at least some pts with noct. enuresis.
However, whether these abnormalities are primary or secondary (eg, to bladder capacity or maturational delay) is not clear

26. Detrusor instability 
 Urodynamics in children who have diurnal incontinence demonstrates significant functional detrusor abnormalities
No clear pattern of UDN abnormality demonstrated in children with primary monosymptomatic noct. Enuresis
Most studies suggest that the incidence of uninhibited bladder activity in children with 1ry monosymptomatic noct. enuresis is similar to the incidence in normal children ( 3-5% )

27. bladder dysfunction should be considered in children who have refractory monosymptomatic primary nocturnal enuresis
When UDN studies performed during sleep, the only difference between enuretic and nonenuretic children is the increased rate of bladder contractions in enuresis

28. Sleep disorders
Parents often describe their children with enuresis as excessively deep sleepers
Excessively deep sleep appears to contribute to nocturnal enuresis in adolescents and adults
Sleep studies show that sleep patterns among children with and without enuresis are similar

29. Nocturnal sleep and bladder monitoring studies by Robert and others (1993) have been able to distinguish 3 types of enuretic episodes:
Type 1:
Gradually elevations in bladder pressure culminate in wetting; .
associated with prominent somatic and visceral reactions
tachycardia, body movements, increasing respirations, and progressive awakening.
The awakening reaction is strong, and the child struggles to keep from wetting.

30. Type 2
A very quick micturition is associated with minimal body movement and visceral signs.
The awakening reaction is very brief, and the struggle to keep from wetting is very limited
Type 3
Complete parasomnia, a total lack of CNS reaction and response to bladder contraction, occurs
neither bladder filling nor bladder contraction registers on the EEG
involuntary voiding occurs without any modification of sleep.

31. These three patterns appear to reflect the various stages in the normal development of nocturnal urinary control and suggest
wetting during sleep is to a great extent determined by CNS maturation.

33. These findings suggest
sleep patterns of enuretics are not different from those of normal children
most enuretics neither have a disorder of arousal nor wet as a consequence of sleeping too deeply
Enuresis is related to delay in CNS development or, more accurately, a dual delay in the development of the perception and inhibition of bladder filling and contraction by the CNS (Koff, 1995).

34. Psychological
Although psychologic abn. have been considered to play a role in noct. enuresis, this relationship has not been proven
perceived adjustment problems tend to improve after resolution of enuresis, suggesting behavioral abnormalities are a result, rather than a cause of the enuresis

35. Deferential diagnosis:
Unrecognized underlying medical disorders
(eg, SCD, seizures, DM, DI , hyperthyroidism)
Encopresis or constipation
Dysfunctional voiding (usually associated with daytime symptoms)
Urinary tract infection
Chronic renal failure
Spinal dysraphism
Psychogenic polydipsia

36. Evaluation: History Presence of daytime wetting or symptoms
Any prolonged period of dryness
Family history of nocturnal enuresis
Frequency and trend of nocturnal enuresis

37. Fluid intake diary
Voiding diary
Stooling diary
Medical history ( diabetes, sickle cell disease or trait, urinary tract infection, gait or neurologic abnormalities)
Social history ( important in secondary enuresis)
Effect of problem on child & family
which interventions the family has tried

38. Physical examination
Usually normal

39. Conditions which reflect medical etiology for enuresis include:
Palpation of stool in the abdomen suggests constipation or encopresis.
Perianal excoriation or vulvovaginitis may indicate pinworm infection
Poor growth and/or hypertension may indicate renal disease.
Presence of abnormalities of the lower lumbosacral spine or neurlolgical abnormalities
Detection of incomplete bladder emptying

40. Urinalysis 
screen for diabetic ketoacidosis, diabetes insipidus, water intoxication, and/or occult urinary tract infection
Imaging — 
Urologic imaging is reserved for
who have significant daytime complaints
h/o UTI not previously evaluated
signs and symptoms of structural urologic abnormalities
Neurologic imaging (MRI spine) is indicated in children who have abnormalities of the lower lumbosacral spine on neurologic examination of the perineum and lower extremities

42. Management of nocturnal enuresis in children
GENERAL PRINCIPLES — 
age at which enuresis is considered to be a "problem" varies depending upon the family
For the child, nocturnal enuresis usually becomes significant only when it interferes with his or her ability to socialize
As a general rule, children younger than seven years of age may be managed expectantly, as the majority will resolve spontaneosly

43. Parents must clearly understand that nocturnal wetting are involuntary on the part of the child
Parent education that Rx may be prolonged, associated with relapses, and may fail in the short term
The parents must be willing to participate, and the family environment must be supportive
The child must be highly motivated to participate in a treatment program

44. Treatment modalities
Motivational therapy
Bladder training
Fluid management
Behavioral alarms
Pharmacological agents

45. Rx is rarely indicated in a child younger than 7yrs
motivational therapy, bladder retention exercises, fluid management are usually tried for 3-6 mo. in motivated family & child
More active intervention (eg, arousal alarm systems, pharmacotherapy) should be considered as the child gets older, social pressures increase, and self-esteem is affected
Pharmacologic agents can be effective in the short-term (eg, for sleepovers or camp attendance), but enuresis alarms are the most effective long-term therapy

46. Motivational therapy
Rewards given to a child for longer period of dryness
leads to significant improvement > 70 %
relapse rate (more than two wet nights in two wks ) is 5 %
Motivational therapy is a good 1st line of therapy for 1ry noct. enuresis, particularly in younger children
If motivational therapy fails to lead to improvement after 3-6 mo., other methods should be tried

47. Bladder training
children with noct. enuresis have a functionally small bladder capacity
Bladder retention training exercises may be undertaken to increase bladder capacity
Bladder training therapy leads to significant improvement 60 %
Successful in 35 %
a trial of this simple behavioral method is recommended before alarms and pharmacologic agents are tried

48. Some authors recommend
Fluid management
 Some authors recommend
to drink 40 % of their total fluid in the morning
40 % in the afternoon
only 20 % in the evening
beverages consumed in the evening caffeine-free
Isolated nighttime fluid restriction, should be compensated in daytime fluid consumption

50. Enuresis alarms
Enuresis alarm is the most effective means of controlling nocturnal enuresis
Enuresis alarms are activated when a sensor, placed in the undergarments or on a bed pad, detects moisture; the arousal device is usually an auditory alarm and/or a vibrating belt or pager

52. Alarm works through conditioning:
the patient learns to wake or inhibit bladder contraction in response to the neurologic conditions present before wetting
The child should F/U 1-2 wks after starting the alarm and then at the end of an 8 -week trial
Therapy with the alarm can be reinitiated for relapse (more than two wet nights in two weeks).
30 % of pts discontinue the alarm for various reasons

53. Alarms appeared to be less immediately effective than desmopressin, but more effective in preventing relapse
Alarms were more effective than tricyclic antidepressants during and after treatment
Relapse rate after stopping therapy is much lower with alarms than with desmopressin

54. Many authors concluded that an ordinary alarm clock is
Alarm clocks
It may be possible to condition some children to wake to void by using an alarm clock
Many authors concluded that an ordinary alarm clock is
safe
Effective
noncontact treatment that does not require an episode of bedwetting to initiate a conditioning

55. PHARMACOLOGIC THERAPY
desmopressin acetate (DDAVP)
tricyclic antidepressants (TCAs)
Other drugs may be beneficial

56. Desmopressin: mechanism of action unclear
Suggested that DDAVP acts on a different receptor, possibly the vasopressin 1b receptor in the brain
Dose given late evening to reduce urine production during sleep
The drug is given either intranasally or orally
It is relatively expensive
A normal functional bladder capacity is necessary for response to desmopressin

57. Dose usually titrated to best effect, increasing the dose every 10 days to the maximum recommended dose
The process usually takes a total of 30 days
The oral tab. is given at 0.2 mg initially (1 tab.) and may be increased to 0.6 mg (3 tab.) as needed over a 2-week trial
The nasal spray is usually begun at 20 micrograms at bedtime, and titrated to max. of 40 micrograms at bedtime

58. 25 % achieves total dryness using desmo.
50 % had significant decrease in nighttime wetting
Similar to TCAs, stopping the medication is associated with high rates of relapse %

59. Desmopressin and TCA appear to be equally effective.
systematic review of 41 randomized trials involving 2760 children comparing desmopressin to other drugs or alarms in the treatment of nocturnal enuresis
Compared with placebo, desmopressin (20 microgram nasal spray) reduced bedwetting by 1.34 nights per week (95% CI ).
Compared with placebo, children treated with desmopressin (20 microgram nasal spray) were more likely to become dry (ie, no episodes for 14 nights) (RR 1.19, 95% CI ).
In contrast to arousal alarms, treatment effects were not sustained after discontinuation of therapy.
Desmopressin and TCA appear to be equally effective.

60. Adverse effects of desmopressin uncommon
Nasal form occasionally causes mild rhinitis
The most serious adverse effect is dilutional hyponatremia, occurs when excess fluids are taken in the evening hours
To prevent this complication, it is recommended that fluid intake be limited to 240 mL on any evening that desmopressin is given

61. Tricyclic antidepressants:
Imipramine, Amitriptyline, and desipramine have been recognized as a useful adjunct in the Rx of enuresis since 1960
Although imipramine is the drug most often used, other TCAs are also effective
TCAs decrease the amount of time spent in REM sleep, stimulate vasopressin secretion, and relax the detrusor muscle.

62. The dose of imipramine is 0.9 - 1.5 mg/kg per day, bedtime
On average, the bedtime dose is 25 mg for children 5-8 years of age and 50 mg for older children
The dose should not exceed 50 mg in children between yrs of age and 75 mg in children 12 years of age
The Effect of imipramine is quick if the dose is adequate
Imipramine should be discontinued if there is no improvement after a three-week trial (at an adequate dose); it may be discontinued abruptly

63. Adverse effects of TCA therapy are relatively uncommon
5 % develop neurologic symptoms including nervousness, personality change, and disordered sleep
The most serious adverse effects of TCAs, involve CVS, including the risk of cardiac conduction disturbances and myocardial depression, particularly in cases of overdose.

64. Other drugs Indomethacin: Rarely used
One small randomized controlled trial found that indomethacin suppository versus placebo significantly increased the number of dry nights in children with primary nocturnal enuresis who were treated for 3 wks
Possible mechanisms of action include removal of the normal inhibitory effect of prostaglandins on the response to vasopressin

65. Anticholinergic drugs:
such as oxybutynin, are not effective in treating monosymptomatic nocturnal enuresis
May be useful in children who also present with significant daytime urgency
combination of anticholinergic therapy and desmopressin may be used in these children in an attempt to increase bladder capacity during sleep

66. Other drugs, including phenmetrazine, amphetamine sulfate, ephedrine, atropine, furosemide, diclofenac, and chlorprotixine have been tried
none of the drugs was better than desmopressin

68. Recommendations in the Rx of monosympotomatic nocturnal enuresis
children < 7yrs therapy should consist primarily of reassurance that spontaneous resolution is likely
Once the child is able to be partially responsible for Rx, motivation and simple behavior therapies are recommended
include reinforcement for dry nights (eg, a sticker calendar)
bladder training exercises,
fluid management, as described above
combination of these
Enuresis alarms or pharmacologic therapy should be considered in children who failed to improve after 3-6 months of behavioral interventions

69. Enuresis alarms are preferred to pharmacologic therapy bcs their effects are sustained after discontinuation and bcs they are associated with fewer S/E
Desmopressin is an effective short-term alternative to the enuresis alarm in patients who are unresponsive to the alarm

70. Similar to desmopressin, TCA are an effective short-term therapy for nocturnal enuresis
their high relapse rate and potentially severe adverse effects make them less appealing than alarm or desmopressin therapy

71. Thank you

72. References
Campbell`s Urology