Nocturnal Enuresis

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Nocturnal Enuresis

• Hann-Chorng Kuo
• Department of Urology
• Buddhist Tzu Chi General Hospital

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Nocturnal Enuresis

• Enuresis piss-a-beds (Greek)
• Enuresis A normal void occurring at an
  inappropriate or socially unacceptable time or
  place
• Nocturnal enuresis Children void in bed while
  asleep and are generally not aroused by the
  wetting
• Monosymptomatic with a familial tendency

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Quantification of Nocturnal Enuresis

• Age children over the age of 5 years
• Frequency number of wet nights per week or
  month the time of wetting at early (first 2
  hours) or late (2 hours before arising) or
  randomly timed
• Amount of wetting The bed is soaking wet or
  smaller amounts
• Arousibility To wake up to a full bladder

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Subtypes of Nocturnal Enuresis

• Primary nocturnal enuresis mono-symptomatic
  bedwetting never have been dry for uninterrupted
  period gt6months
• Onset nocturnal enuresis
• Familial nocturnal enuresis
• Nocturnal polyuria enuresis urine production gt
  functional bladder capacity on wet nights,
  nocturia on dry nights

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Epidemiology of Nocturnal Enuresis

• 15 20 of 5-year-olds, 5 of 10-year-olds, 2-3
  of all adolescents wet the bed at least 1/month
• Enuresis has a 15 per year spontaneous
  resolution rate
• Bed wetting is the cause of significant
  psychosocial stress, especially in older children

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Genetic Factors for Nocturnal enuresis

• Family history Increased incidence of enuresis
  in children whose parents were enuretic, 77 in
  both parents enuretic, 43 in only one parent
  enuretic, 15 no parental history of enuresis
• Among boys 70 monozygotic and 31 dizygotic,
  among girls 65 vs 44 were enuretic

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Genetic Defects in NE

• Vasopressin-neurophysin II (VPNP II) gene is
  defective in familial nephrogenic diabetic
  insipidus (FNDI), but not in familial
  mono-symptomatic NE, on chromosome 20
• Disease phenotype of nocturnal enuresis was
  associated with 2 markers, 13q13 13q14.2,
  locating at long arm of chromosome 13 (ENUR 1)

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Genetic factors and Response to Vasopressin
Therapy

• 91 of enuretic patients with family history had
  good response to vasopressin vs only 7 of no
  family history
• Response is confined to those with nocturnal
  polyuria
• ENUR 1 cannot be responsible for the enuretic
  phenotype in all affected families

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Normal Micturition

• Bladder capacity is reached
• Stimulating stretch receptors in bladder wall
• Bladder neck descent and open
• External sphincter reflexly opens
• Detrusor contraction starts
• Urine is expelled from the urethra under pressure

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Bladder Control

• Under 6 month old, frequent reflex voiding day
  and night
• 6 to 12 month old, bladder empty is less frequent
  because of CNS inhibition
• 1 to 2 years, child recognizes when the bladder
  is full and can communicate verbally
• 3 to 4 years old, child can postpone urination
• The awareness of bladder fullness increases up to
  age 5, when the child can delayed voiding on
  command

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Night time Bladder Control

• In children aged 2 to 12 months, voided 1 to 8
  times during 4 hours observation
• 78 of children voided within 10minutes of waking
  (arousal in response to bladder fullness)
• More than 50 of children aged 3 years gt81 of
  4 years are reported generally is dry at night

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Development and N E

• Increased incidence of developmental delay in
  enuretic children
• Delayed motor development is associated with a
  delay in bladder control
• Nocturnal enuresis is more prevalent in boys than
  girls, which is associated with maturation delay
• Small bladder capacity is controversial

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Delay in Bladder Control

• Detrusor instability is an important pathogenic
  factor in NE children
• Day time incontinence, urgency, frequency, small
  bladder capacity might be associated with a
  dyssynergic pelvic floor muscle during voiding
• Recent studies indicated enuretic children do not
  have daytime DI, not respond to oxybutynine

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Night time Bladder Control

• Functional bladder capacity is smaller than
  non-enuretic children
• Bladder capacity is less important than
  perception of bladder contractions
• A smaller bladder capacity may be a consequence
  rather than a cause of NE
• 70 of NE children had a stable bladder, 30 had
  DI when asleep although a stable bladder was
  detected in daytime

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Balance between Bladder capacity and Nocturnal
urine vol

• Nocturnal urine production
• Functional bladder capacity
• Enuresis will only result if nocturnal bladder
  capacity is exceeded
• Enuretic children only experienced wet nights
  when nocturnal urine volume exceeded bladder
  volume

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Balance between Bladder capacity and Nocturnal
urine vol
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CNS Control of Bladder Function

• A developmental delay in CNS control of bladder
  function might be a cause of NE
• A defect in efferent (failed to inhibit detrusor
  contraction) or afferent (failed to respond to
  bladder fullness or contraction) pathways might
  produce NE
• Enuretic children failed to contract pelvic floor
  muscles (silent EMG) in response to bladder
  filling during sleep

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Arousal and Nocturnal enuresis

• Locus coeruleus in brain stem is responsible for
  cortical arousal of stimuli, releasing
  noradrenaline, which in turn regulates
  vasopressin secretion from hypothalamus
• Deficit in vasopressin secretion results in
  polyuria and impair cortical arousal
• Vasopresin can increase alertness in rats
• Abnormal vasopressin secretion pattern in
  enuretics withnocturnal polyuria

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Arousal Dysfunction in PNE
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Arousal Defects in Enuretics

• Enuretic children are heavier sleepers compared
  with non-enuretics
• Arousal was successful on only 9.3 of attempts
  in enuretics, compared with 39.7 in the controls
• Sleep pattern of the enuretics is similar to that
  of normal children
• Enuresis occurs in all sleep stages

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Categories of Enuresis

• Type I detectable EEG response to bladder
  distension and a stable CMG, 58
• Type IIa no EEG response to bladder distension,
  stable CMG, 10
• Type IIb no EEG response to bladder distension,
  unstable CMG during sleep, 32
• Type I II mild to severe arousal defects

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Arousal and Bladder Function in Nocturnal enuresis
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Lack of Diurnal Rhythmicity of Plasma Vasopressin
in Enuretics

• Normal children have a diurnal rhythm of plasma
  vasopressin and urinary output with a nocturnal
  increase in plasma vasopressin, 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

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Lack of Diurnal Rhythmicity of Plasma Vasopressin
in Enuretics
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Plasma vasopressin level in NE
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Urine Osmolarity in NE
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Nocturnal urine volume in NE
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Treatment of Nocturnal Enuresis

• Primary nocturnal enuresis (PNE or MNE)
• with or without nocturnal polyuria
• desmopressin responder or non-responder
• arousal dysfunction or bladder dysfunction
• Secondary nocturnal enuresis
• dysfunctionalvoiding
• neurogenic voiding dysfunction
• psychological distress

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Nocturnal Urine Control

• In normal subjects, urine production decreases
  during night time
• Nocturnal urine production is about half of that
  in the daytime
• A significant proportion of MNE patients lost the
  circadian rhythm of vasopressin secretion and
  produce large volume of diluted urine
• Polyuria is an important factor in ¾ of the
  enuretic children

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Nocturnal polyuria and Vasopressin

• Some enuretic children with NP (nocturnal
  polyuria) have good response to vasopressin
• A subgroup of enuretic children with NP have a
  normal rhythm of vasopressin secretion, and not
  respond to DDAVP
• A defect in renal sensitivity to vasopressin and
  DDAVP is likely
• Enuretic children without NP and have a
  normalvasopressin rhythm do not respond to DDAVP

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Treatment of Nocturnal Enuresis

• Conditioning therapy Alarm system or dry-bed
  training,effective in about 30-80
• Medcal therapy (1) Tricyclic antidepressant
  (TCA), imipramine, amitriptyline effective in
  10-50 (author 24)
• (2) anti-cholinergics
• (3) desmopressin (DDAVP)
• Side effect in combination medical therapy

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DDAVP Therapy in Nocturnal Enuresis in Children

• DDAVP in dose of 10-20 ug intranasally is
  effective in 70 of children with PNE
• After discontinuing DDAVP for 3months, 21
  remained dry without medication
• 20 ug is adequate in treating PNE, in children
  not responded to 20ug, 40ug did not effective
• No serious adverse effect

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DDAVP Experience in Hualien

• 34 patients aged 5 to 24 years (10 4 years)
• Responserate was 91 under active treatment with
  DDAVP 20 ug, and 39 off drug for 1 month
• During treatment, 22/34 were dry(67), 8/34(24)
  improved to 3 wet nights/week and 3/34(9) were
  wet gt4/week
• Dose of 20ug for 8 weeks is adequate

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Double blind placebo control study of DDAVP in PNE
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The Effectiveness of DDAVP and Placebo in PNE
DDAVP Placebo DC drug 1 month
Dry 10(56) 3(17) 2(11) 2(11)
Gr I Improved 7(39) 11(61) 10(56) 6(33)
N18 Failed 1(5) 4(22) 6(33) 10(56)

Dry 12(80) 1(7) 1(7)
Gr II Improved 1(7) 8(53) 4(27)
N15 Failed 2(13) 6(40) 10(66)
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Secondary Nocturnal Enuresis

• Psychological factors stress, anxiety,
  depression
• Neurogenic detrusor underactivity and overflow
  incontinence
• Dysfunctional voiding
• Urinary tract infection
• Bladder outlet obstruction
• Diurnal incontinence

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Diurnal enuresis

• Detrusor instability is commonly found
• Urgency frequency and urge incontinence
• Pelvic floor spasticity and dysfunctional voiding
• May associated with constipation or fecal
  incontinence
• Urodynamic study in patients not respond to
  oxybutynine

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Nocturnal enuresis in Adults

• Monosymptomatic PNE exists in 0.5- 1
• Desmopressin 200 400 micro g for 3 months
• 35 of patients became dry after desmopressin
  remained dry without therapy
• Nocturia occurred in 75 of enuretics, but in
  only 5 of the healthy controls

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Secondary Nocturnal Enuresis in Adults

• Bladder outlet obstruction in elderly men
  (progressive BPH obstruction)
• Detrusor underactivity and overflow incontinence
  in women (after radical hysterectomy or APR)
• Detrusor overactivity in neurogenic voiding
  dysfunction (stroke, Parkinsons disease)
• Idiopathic (urethral instability ?)

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Treatment of Adult Nocturnal Enuresis

• DDAVP in patients proven to have nocturnal
  polyuria (nocturnal urine volume gt 35 daily
  urine volume, or gt900ml/N)
• Oxybutynine in patients proven to have DI
• Imipramine or methylephedrine in patients
  suspicious to have urethral incompetence
• Pelvic floor muscle exercises or functional
  electrostimulation might be helpful

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Psychological Factors in MNE

• Psychological distress in not significantly
  higher in enuretics than clinical controls
• Psychological distress is more common in
  secondary enuresis and day wetting than primary
  enuretics and bed wetting
• Enuretic girls had higher risk in developing
  psychological distress

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Psychological symptoms

• Feel bewildered and humiliated and are different
  from peers
• Often teased and bullied because of enuresis
• Decline to participate activities and overnight
  stay or invite friends to visit
• Worry their bedroom smells unclean andnot allow
  friends to enter it
• Aware enuresis results in extra work and expense
  for their parents

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Impact of Psychological Stress

• Enuresis occurs in mental retardation, autism,
  attention deficit disorder, dysfunction in motor
  control or perception
• Enuresis is more common in lower socio-economic
  groups, in large overcrowded family, and in
  children living in institution
• Enuresis is associated with short stature,
  reflecting deficiency of growth hormone secretion
  and vasopression deficiency

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Conclusions

• Nocturnal enuresis has a multifactorial etiology
• It may be best regarded as groups of conditions
• 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

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No More Bed Wetting