排尿障礙治療中心版權所有 Nocturnal Enuresis Hann-Chorng Kuo Department of Urology Buddhist Tzu Chi General Hospital

排尿障礙治療中心版權所有

Nocturnal EnuresisNocturnal Enuresis

Hann-Chorng KuoHann-Chorng Kuo

Department of UrologyDepartment of Urology

Buddhist Tzu Chi General HospitalBuddhist Tzu Chi General Hospital


Nocturnal EnuresisNocturnal Enuresis

Enuresis – piss-a-beds (Greek)Enuresis – piss-a-beds (Greek) Enuresis – A Enuresis – A normal voidnormal void occurring at an in occurring at an in

appropriate or socially unacceptable time or appropriate or socially unacceptable time or placeplace

Nocturnal enuresis – Children void in bed wNocturnal enuresis – Children void in bed while asleep and are generally not aroused by hile asleep and are generally not aroused by the wettingthe wetting

Monosymptomatic with a familial tendencyMonosymptomatic with a familial tendency


Quantification of Quantification of Nocturnal EnuresisNocturnal Enuresis

Age: children over the age of 5 yearsAge: children over the age of 5 years Frequency: number of wet nights per week Frequency: number of wet nights per week

or month; the time of wetting at early (first or month; the time of wetting at early (first 2 hours) or late (2 hours before arising) or r2 hours) or late (2 hours before arising) or randomly timedandomly timed

Amount of wetting: The bed is soaking wet Amount of wetting: The bed is soaking wet or smaller amountsor smaller amounts

Arousibility: To wake up to a full bladderArousibility: To wake up to a full bladder


Subtypes of Subtypes of Nocturnal EnuresisNocturnal Enuresis

Primary nocturnal enuresis: mono-symptomPrimary nocturnal enuresis: mono-symptomatic bedwetting never have been dry for uniatic bedwetting never have been dry for uninterrupted period >6monthsnterrupted period >6months

Onset nocturnal enuresisOnset nocturnal enuresis Familial nocturnal enuresisFamilial nocturnal enuresis Nocturnal polyuria enuresis : urine productiNocturnal polyuria enuresis : urine producti

on > functional bladder capacity on wet nigon > functional bladder capacity on wet nights, nocturia on dry nightshts, nocturia on dry nights


Epidemiology of Epidemiology of Nocturnal EnuresisNocturnal Enuresis

15 – 20% of 5-year-olds, 5% of 10-year-15 – 20% of 5-year-olds, 5% of 10-year-olds, 2-3 % of all adolescents wet the bed at olds, 2-3 % of all adolescents wet the bed at least 1/monthleast 1/month

Enuresis has a 15% per year spontaneous Enuresis has a 15% per year spontaneous resolution rateresolution rate

Bed wetting is the cause of significant Bed wetting is the cause of significant psychosocial stress, especially in older psychosocial stress, especially in older childrenchildren


Genetic Factors for Genetic Factors for Nocturnal enuresisNocturnal enuresis

Family history: Increased incidence of enurFamily history: Increased incidence of enuresis in children whose parents were enuretic,esis in children whose parents were enuretic, 77% in both parents enuretic, 43% in only 77% in both parents enuretic, 43% in only one parent enuretic, 15% no parental history one parent enuretic, 15% no parental history of enuresisof enuresis

Among boys 70% monozygotic and 31% diAmong boys 70% monozygotic and 31% dizygotic, among girls 65% vs 44% were enurzygotic, among girls 65% vs 44% were enureticetic


Genetic Defects in NEGenetic Defects in NE

Vasopressin-neurophysin II (VPNP II) gene Vasopressin-neurophysin II (VPNP II) gene is defective in familial nephrogenic diabetic is defective in familial nephrogenic diabetic insipidus (FNDI), but not in familial mono-insipidus (FNDI), but not in familial mono-symptomatic NE, on chromosome 20symptomatic NE, on chromosome 20

Disease phenotype of nocturnal enuresis waDisease phenotype of nocturnal enuresis was associated with 2 markers, 13q13 & 13q1s associated with 2 markers, 13q13 & 13q14.2, locating at long arm of chromosome 13 4.2, locating at long arm of chromosome 13 (ENUR 1)(ENUR 1)


Genetic factors and Response to Genetic factors and Response to Vasopressin TherapyVasopressin Therapy

91% of enuretic patients with family history 91% of enuretic patients with family history had good response to vasopressin vs only 7had good response to vasopressin vs only 7% of no family history% of no family history

Response is confined to those with nocturnaResponse is confined to those with nocturnal polyurial polyuria

ENUR 1 cannot be responsible for the enureENUR 1 cannot be responsible for the enuretic phenotype in all affected familiestic phenotype in all affected families


Normal MicturitionNormal Micturition

Bladder capacity is reachedBladder capacity is reached Stimulating stretch receptors in bladder wallStimulating stretch receptors in bladder wall Bladder neck descent and openBladder neck descent and open External sphincter reflexly opensExternal sphincter reflexly opens Detrusor contraction startsDetrusor contraction starts Urine is expelled from the urethra under preUrine is expelled from the urethra under pre

ssuressure


Bladder ControlBladder Control

Under 6 month old, frequent reflex voiding day Under 6 month old, frequent reflex voiding day and nightand night

6 to 12 month old, bladder empty is less frequent 6 to 12 month old, bladder empty is less frequent because of CNS inhibitionbecause of CNS inhibition

1 to 2 years, child recognizes when the bladder is 1 to 2 years, child recognizes when the bladder is full and can communicate verballyfull and can communicate verbally

3 to 4 years old, child can postpone urination3 to 4 years old, child can postpone urination The awareness of bladder fullness increases up to The awareness of bladder fullness increases up to

age 5, when the child can delayed voiding on age 5, when the child can delayed voiding on commandcommand


Night time Bladder ControlNight time Bladder Control

In children aged 2 to 12 months, voided 1 to In children aged 2 to 12 months, voided 1 to 8 times during 4 hours observation8 times during 4 hours observation

78% of children voided within 10minutes of 78% of children voided within 10minutes of waking (arousal in response to bladder waking (arousal in response to bladder fullness)fullness)

More than 50% of children aged 3 years & More than 50% of children aged 3 years & >81% of 4 years are reported generally is >81% of 4 years are reported generally is dry at nightdry at night


Development and N EDevelopment and N E

Increased incidence of developmental delay Increased incidence of developmental delay in enuretic childrenin enuretic children

Delayed motor development is associated wDelayed motor development is associated with a delay in bladder controlith a delay in bladder control

Nocturnal enuresis is more prevalent in boyNocturnal enuresis is more prevalent in boys than girls, which is associated with maturas than girls, which is associated with maturation delaytion delay

Small bladder capacity is controversialSmall bladder capacity is controversial


Delay in Bladder Control Delay in Bladder Control

Detrusor instability is an important pathogeDetrusor instability is an important pathogenic factor in NE childrennic factor in NE children

Day time incontinence, urgency, frequency, Day time incontinence, urgency, frequency, small bladder capacity might be associated small bladder capacity might be associated with a dyssynergic pelvic floor muscle duriwith a dyssynergic pelvic floor muscle during voidingng voiding

Recent studies indicated enuretic children dRecent studies indicated enuretic children do not have daytime DI, not respond to oxybo not have daytime DI, not respond to oxybutynineutynine


Night time Bladder ControlNight time Bladder Control

Functional bladder capacity is smaller than Functional bladder capacity is smaller than non-enuretic childrennon-enuretic children

Bladder capacity is less important than percBladder capacity is less important than perception of bladder contractionseption of bladder contractions

A smaller bladder capacity may be a conseqA smaller bladder capacity may be a consequence rather than a cause of NEuence rather than a cause of NE

70% of NE children had a stable bladder, 3070% of NE children had a stable bladder, 30% had DI when asleep although a stable bla% had DI when asleep although a stable bladder was detected in daytimedder was detected in daytime


Balance between Bladder capacitBalance between Bladder capacity and Nocturnal urine voly and Nocturnal urine vol

Nocturnal urine productionNocturnal urine production Functional bladder capacityFunctional bladder capacity Enuresis will only result if nocturnal bladdeEnuresis will only result if nocturnal bladde

r capacity is exceededr capacity is exceeded Enuretic children only experienced wet nighEnuretic children only experienced wet nigh

ts when nocturnal urine volume exceeded blts when nocturnal urine volume exceeded bladder volumeadder volume


Balance between Bladder capacitBalance between Bladder capacity and Nocturnal urine voly and Nocturnal urine vol


CNS Control of Bladder CNS Control of Bladder FunctionFunction

A developmental delay in CNS control of blA developmental delay in CNS control of bladder function might be a cause of NEadder function might be a cause of NE

A defect in efferent (failed to inhibit detrusoA defect in efferent (failed to inhibit detrusor contraction) or afferent (failed to respond tr contraction) or afferent (failed to respond to bladder fullness or contraction) pathways o bladder fullness or contraction) pathways might produce NEmight produce NE

Enuretic children failed to contract pelvic flEnuretic children failed to contract pelvic floor muscles (silent EMG) in response to blaoor muscles (silent EMG) in response to bladder filling during sleepdder filling during sleep


Arousal and Nocturnal enuresisArousal and Nocturnal enuresis

Locus coeruleus in brain stem is responsible Locus coeruleus in brain stem is responsible for cortical arousal of stimuli, releasing norfor cortical arousal of stimuli, releasing noradrenaline, which in turn regulates vasopresadrenaline, which in turn regulates vasopressin secretion from hypothalamussin secretion from hypothalamus

Deficit in vasopressin secretion results in poDeficit in vasopressin secretion results in polyuria and impair cortical arousallyuria and impair cortical arousal

Vasopresin can increase alertness in ratsVasopresin can increase alertness in rats Abnormal vasopressin secretion pattern in eAbnormal vasopressin secretion pattern in e

nuretics withnocturnal polyurianuretics withnocturnal polyuria


Arousal Dysfunction in PNEArousal Dysfunction in PNE


Arousal Defects in EnureticsArousal Defects in Enuretics

Enuretic children are heavier sleepers compEnuretic children are heavier sleepers compared with non-enureticsared with non-enuretics

Arousal was successful on only 9.3% of atteArousal was successful on only 9.3% of attempts in enuretics, compared with 39.7% in tmpts in enuretics, compared with 39.7% in the controlshe controls

Sleep pattern of the enuretics is similar to thSleep pattern of the enuretics is similar to that of normal childrenat of normal children

Enuresis occurs in all sleep stagesEnuresis occurs in all sleep stages


Categories of EnuresisCategories of Enuresis

Type I: detectable EEG response to bladder Type I: detectable EEG response to bladder distension and a stable CMG, 58%distension and a stable CMG, 58%

Type IIa: no EEG response to bladder disteType IIa: no EEG response to bladder distension, stable CMG, 10%nsion, stable CMG, 10%

Type IIb: no EEG response to bladder disteType IIb: no EEG response to bladder distension, unstable CMG during sleep, 32%nsion, unstable CMG during sleep, 32%

Type I & II: mild to severe arousal defectsType I & II: mild to severe arousal defects


Arousal and Bladder Function in Arousal and Bladder Function in Nocturnal enuresisNocturnal enuresis


Lack of Diurnal Rhythmicity of PLack of Diurnal Rhythmicity of Plasma Vasopressin in Enureticslasma Vasopressin in Enuretics

Normal children have a diurnal rhythm of plNormal children have a diurnal rhythm of plasma vasopressin and urinary output with a asma vasopressin and urinary output with a nocturnal increase in plasma vasopressin, dnocturnal increase in plasma vasopressin, decrease in urinary excretion rate, and increaecrease in urinary excretion rate, and increase in urine osmolarityse in urine osmolarity

Enuretics have an abnormal rhythm of plasEnuretics have an abnormal rhythm of plasma vasopressin and urinary output with nocma vasopressin and urinary output with nocturnal low vasopressin, large urinary excretiturnal low vasopressin, large urinary excretion rate, and lower urinary osmolarityon rate, and lower urinary osmolarity


Lack of Diurnal Rhythmicity of PLack of Diurnal Rhythmicity of Plasma Vasopressin in Enureticslasma Vasopressin in Enuretics


Plasma vasopressin level in NEPlasma vasopressin level in NE


Urine Osmolarity in NEUrine Osmolarity in NE


Nocturnal urine volume in NENocturnal urine volume in NE


Treatment of Nocturnal EnuresisTreatment of Nocturnal Enuresis

Primary nocturnal enuresis (PNE or MNE)Primary nocturnal enuresis (PNE or MNE) with or without nocturnal polyuriawith or without nocturnal polyuria desmopressin responder or non-responderdesmopressin responder or non-responder arousal dysfunction or bladder dysfunctionarousal dysfunction or bladder dysfunction Secondary nocturnal enuresisSecondary nocturnal enuresis dysfunctionalvoidingdysfunctionalvoiding neurogenic voiding dysfunctionneurogenic voiding dysfunction psychological distresspsychological distress


Nocturnal Urine Control Nocturnal Urine Control

In normal subjects, urine production decreases durIn normal subjects, urine production decreases during night timeing night time

Nocturnal urine production is about half of that in Nocturnal urine production is about half of that in the daytimethe daytime

A significant proportion of MNE patients lost the A significant proportion of MNE patients lost the circadian rhythm of vasopressin secretion and procircadian rhythm of vasopressin secretion and produce large volume of diluted urineduce large volume of diluted urine

Polyuria is an important factor in ¾ of the enuretic Polyuria is an important factor in ¾ of the enuretic childrenchildren


Nocturnal polyuria and VasopresNocturnal polyuria and Vasopressinsin

Some enuretic children with NP (nocturnal polyuriSome enuretic children with NP (nocturnal polyuria) have good response to vasopressina) have good response to vasopressin

A subgroup of enuretic children with NP have a nA subgroup of enuretic children with NP have a normal rhythm of vasopressin secretion, and not resormal rhythm of vasopressin secretion, and not respond to DDAVPpond to DDAVP

A defect in renal sensitivity to vasopressin and DDA defect in renal sensitivity to vasopressin and DDAVP is likelyAVP is likely

Enuretic children without NP and have a normalvaEnuretic children without NP and have a normalvasopressin rhythm do not respond to DDAVPsopressin rhythm do not respond to DDAVP


Treatment of Nocturnal EnuresisTreatment of Nocturnal Enuresis

Conditioning therapy: Alarm system or dry-Conditioning therapy: Alarm system or dry-bed training,effective in about 30-80%bed training,effective in about 30-80%

Medcal therapy: (1) Tricyclic antidepressant Medcal therapy: (1) Tricyclic antidepressant (TCA), imipramine, amitriptyline effective i(TCA), imipramine, amitriptyline effective in 10-50% (author 24%)n 10-50% (author 24%)

(2) anti-cholinergics(2) anti-cholinergics

(3) desmopressin (DDAVP)(3) desmopressin (DDAVP) Side effect in combination medical therapySide effect in combination medical therapy


DDAVP Therapy in DDAVP Therapy in Nocturnal Enuresis in ChildrenNocturnal Enuresis in Children

DDAVP in dose of 10-20 ug intranasally is DDAVP in dose of 10-20 ug intranasally is effective in 70% of children with PNEeffective in 70% of children with PNE

After discontinuing DDAVP for 3months, 2After discontinuing DDAVP for 3months, 21% remained dry without medication1% remained dry without medication

20 ug is adequate in treating PNE, in childre20 ug is adequate in treating PNE, in children not responded to 20ug, 40ug did not effectn not responded to 20ug, 40ug did not effectiveive

No serious adverse effectNo serious adverse effect


DDAVP Experience in HualienDDAVP Experience in Hualien

34 patients aged 5 to 24 years (1034 patients aged 5 to 24 years (10++ 4 years) 4 years) Responserate was 91% under active treatmeResponserate was 91% under active treatme

nt with DDAVP 20 ug, and 39% off drug font with DDAVP 20 ug, and 39% off drug for 1 monthr 1 month

During treatment, 22/34 were dry(67%), 8/3During treatment, 22/34 were dry(67%), 8/34(24%) improved to 3 wet nights/week and 4(24%) improved to 3 wet nights/week and 3/34(9%) were wet >4/week3/34(9%) were wet >4/week

Dose of 20ug for 8 weeks is adequateDose of 20ug for 8 weeks is adequate


Double blind placebo control Double blind placebo control study of DDAVP in PNEstudy of DDAVP in PNE


The Effectiveness of DDAVP The Effectiveness of DDAVP and Placebo in PNEand Placebo in PNE

DDAVPDDAVP PlaceboPlacebo DC drugDC drug 1 month1 month

DryDry 10(56%)10(56%) 3(17%)3(17%) 2(11%)2(11%) 2(11%)2(11%)

Gr IGr I ImprovedImproved 7(39%)7(39%) 11(61%)11(61%) 10(56%)10(56%) 6(33%)6(33%)

N=18N=18 FailedFailed 1(5%)1(5%) 4(22%)4(22%) 6(33%)6(33%) 10(56%)10(56%)

DryDry 12(80%)12(80%) 1(7%)1(7%) 1(7%)1(7%)

Gr IIGr II ImprovedImproved 1(7%)1(7%) 8(53%)8(53%) 4(27%)4(27%)

N=15N=15 FailedFailed 2(13%)2(13%) 6(40%)6(40%) 10(66%)10(66%)


Secondary Nocturnal EnuresisSecondary Nocturnal Enuresis

Psychological factors: stress, anxiety, deprePsychological factors: stress, anxiety, depressionssion

Neurogenic detrusor underactivity and overNeurogenic detrusor underactivity and overflow incontinenceflow incontinence

Dysfunctional voidingDysfunctional voiding Urinary tract infectionUrinary tract infection Bladder outlet obstructionBladder outlet obstruction Diurnal incontinenceDiurnal incontinence


Diurnal enuresisDiurnal enuresis

Detrusor instability is commonly foundDetrusor instability is commonly found Urgency frequency and urge incontinenceUrgency frequency and urge incontinence Pelvic floor spasticity and dysfunctional voiPelvic floor spasticity and dysfunctional voi

dingding May associated with constipation or fecal inMay associated with constipation or fecal in

continence continence Urodynamic study in patients not respond tUrodynamic study in patients not respond t

o oxybutynineo oxybutynine


Nocturnal enuresis in AdultsNocturnal enuresis in Adults

Monosymptomatic PNE exists in 0.5- 1%Monosymptomatic PNE exists in 0.5- 1% Desmopressin 200 – 400 micro g for 3 montDesmopressin 200 – 400 micro g for 3 mont

hshs 35% of patients became dry after desmopre35% of patients became dry after desmopre

ssin remained dry without therapyssin remained dry without therapy Nocturia occurred in 75% of enuretics, but iNocturia occurred in 75% of enuretics, but i

n only 5% of the healthy controlsn only 5% of the healthy controls


Secondary Nocturnal Enuresis Secondary Nocturnal Enuresis in Adultsin Adults

Bladder outlet obstruction in elderly men (pBladder outlet obstruction in elderly men (progressive BPH obstruction)rogressive BPH obstruction)

Detrusor underactivity and overflow incontiDetrusor underactivity and overflow incontinence in women (after radical hysterectomy nence in women (after radical hysterectomy or APR)or APR)

Detrusor overactivity in neurogenic voiding Detrusor overactivity in neurogenic voiding dysfunction (stroke, Parkinson’s disease)dysfunction (stroke, Parkinson’s disease)

Idiopathic (urethral instability ?)Idiopathic (urethral instability ?)


Treatment of Treatment of Adult Nocturnal EnuresisAdult Nocturnal Enuresis

DDAVP in patients proven to have nocturnDDAVP in patients proven to have nocturnal polyuria (nocturnal urine volume > 35% al polyuria (nocturnal urine volume > 35% daily urine volume, or >900ml/N)daily urine volume, or >900ml/N)

Oxybutynine in patients proven to have DIOxybutynine in patients proven to have DI Imipramine or methylephedrine in patients sImipramine or methylephedrine in patients s

uspicious to have urethral incompetenceuspicious to have urethral incompetence Pelvic floor muscle exercises or functional ePelvic floor muscle exercises or functional e

lectrostimulation might be helpfullectrostimulation might be helpful


Psychological Factors in MNEPsychological Factors in MNE

Psychological distress in not significantly hiPsychological distress in not significantly higher in enuretics than clinical controlsgher in enuretics than clinical controls

Psychological distress is more common in sPsychological distress is more common in secondary enuresis and day wetting than priecondary enuresis and day wetting than primary enuretics and bed wettingmary enuretics and bed wetting

Enuretic girls had higher risk in developing Enuretic girls had higher risk in developing psychological distresspsychological distress


Psychological symptomsPsychological symptoms

Feel bewildered and humiliated and are diffFeel bewildered and humiliated and are different from peerserent from peers

Often teased and bullied because of enuresisOften teased and bullied because of enuresis Decline to participate activities and overnigDecline to participate activities and overnig

ht stay or invite friends to visitht stay or invite friends to visit Worry their bedroom smells unclean andnot Worry their bedroom smells unclean andnot

allow friends to enter itallow friends to enter it Aware enuresis results in extra work and exAware enuresis results in extra work and ex

pense for their parentspense for their parents


Impact of Psychological StressImpact of Psychological Stress

Enuresis occurs in mental retardation, autisEnuresis occurs in mental retardation, autism, attention deficit disorder, dysfunction in m, attention deficit disorder, dysfunction in motor control or perceptionmotor control or perception

Enuresis is more common in lower socio-ecEnuresis is more common in lower socio-economic groups, in large overcrowded familonomic groups, in large overcrowded family, and in children living in institutiony, and in children living in institution

Enuresis is associated with short stature, refEnuresis is associated with short stature, reflecting deficiency of growth hormone secretlecting deficiency of growth hormone secretion and vasopression deficiencyion and vasopression deficiency


ConclusionsConclusions

Nocturnal enuresis has a multifactorial etiolNocturnal enuresis has a multifactorial etiologyogy

It may be best regarded as groups of conditiIt may be best regarded as groups of conditionsons

A 15% annual spontaneous cure rateA 15% annual spontaneous cure rate Treatment should match to etiologiesTreatment should match to etiologies Balance between bladder functional capacitBalance between bladder functional capacit

y and nocturnal urine output appear to be thy and nocturnal urine output appear to be the most importante most important


No More Bed WettingNo More Bed Wetting

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排尿障礙治療中心 版權所有 Nocturnal Enuresis Hann-Chorng Kuo Department of Urology Buddhist Tzu Chi General Hospital

排尿障礙治療中心版權所有 Nocturnal Enuresis Hann-Chorng Kuo Department of Urology Buddhist Tzu Chi General Hospital