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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
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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
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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
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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
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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
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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
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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)
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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
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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
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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
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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
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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
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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
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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
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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
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Balance between Bladder capacitBalance between Bladder capacity and Nocturnal urine voly and Nocturnal urine vol
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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
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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
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Arousal Dysfunction in PNEArousal Dysfunction in PNE
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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
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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
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Arousal and Bladder Function in Arousal and Bladder Function in Nocturnal enuresisNocturnal enuresis
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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
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Lack of Diurnal Rhythmicity of PLack of Diurnal Rhythmicity of Plasma Vasopressin in Enureticslasma Vasopressin in Enuretics
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Plasma vasopressin level in NEPlasma vasopressin level in NE
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Urine Osmolarity in NEUrine Osmolarity in NE
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Nocturnal urine volume in NENocturnal urine volume in NE
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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
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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
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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
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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
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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
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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
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Double blind placebo control Double blind placebo control study of DDAVP in PNEstudy of DDAVP in PNE
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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%)
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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
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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
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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
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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 ?)
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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
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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
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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
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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
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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
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No More Bed WettingNo More Bed Wetting
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