Pan
African
Urological
Surgeons’
Association
African
Journal
of
Urology
www.ees.elsevier.com/afju www.sciencedirect.com
Review
Pediatric
urinary
incontinence:
Classification,
evaluation,
and
management
A.J.
Schaeffer
∗,
D.A.
Diamond
DepartmentofUrology,BostonChildren’sHospital,Boston,MA,USA
Received17October2013;accepted30October2013
KEYWORDS Urinaryincontinence; Diurnalenuresis; Nocturnalenuresis; Pediatrics Abstract
Objective:Toreviewtheclassification,evaluation,andmanagementofpediatricurinaryincontinence.
Methods:Anexaminationoftextsandpeer-reviewedliteraturewasperformedtoidentifysubjectmatter
relevanttothestatedobjectives,withtheexperienceoftheseniorauthorusedincaseswheretheliterature
failedtoprovideguidance.
Results:Onthebasisofourreview,weidentifiedtheInternationalChildren’sContinenceSociety’s(ICCS)
statementstandardizingtheterminologyforlowerurinarytractfunctioninchildrenandpresentalogical
classificationschemeforincontinence.Afteranepidemiologyreview,wediscusstheappropriateevaluation
oftheincontinentchild,ofwhichthecornerstonesareadetailedhistoryandthoroughphysicalexam.
Finally,aconcisediscussionofthemanagementofdaytimeincontinence,nocturnalenuresis,andneurogenic
andanatomicincontinenceispresented,withdeferencetoevidence-basedapproacheswhereavailable.
Dependingonthetypeofincontinence,themanagementstrategiescanincludebehavioral,pharmacologic,
and/orsurgicalapproaches.
Conclusion:Pediatricurinaryincontinenceisacommonconditionwhich,afterappropriateevaluation,can
besuccessfullytreated.
©2013PanAfricanUrologicalSurgeons’Association.ProductionandhostingbyElsevierB.V.
Abbreviations: UI,urinaryincontinence;ICCS,InternationalChildren’sContinenceSociety;PVR,postvoidresidual(urine);MNE,monosymptomatic nocturnalenuresis;NMNE,non-monosymptomaticnocturnalenuresis;FDA,UnitedStatesFoodandDrugAdministration;LUTS,lowerurinarytract symptoms;VCUG,voidingcystourethrogram;EMG,electromyography;DDAVP,desmopressin;TCA,tricyclicantidepressant;TENS,transcutaneous electricalnervestimulation;PTNS,posteriortibialnervestimulation;NGB,neurogenicbladder;BTX-A,onabotulinumtoxin–typeA;CIC,clean intermittentcatheterization;AUS,artificialurethralsphincter.
∗Correspondingauthor.Permanentaddress:BostonChildren’sHospital,DepartmentofUrology,300LongwoodAvenue,Hunnewell390,Boston,
MA02115,USA.Tel.:+16173553341;fax:+16177300474.
E-mailaddresses:aschaeffer78@gmail.com,anthony.schaeffer@childrens.harvard.edu(A.J.Schaeffer). PeerreviewunderresponsibilityofPanAfricanUrologicalSurgeons’Association.
1110-5704©2013PanAfricanUrologicalSurgeons’Association. ProductionandhostingbyElsevierB.V.
http://dx.doi.org/10.1016/j.afju.2013.10.001
Open access under CC BY-NC-ND license.
2 A.J.Schaeffer,D.A.Diamond Introduction
Thepurposeofthisarticleistointroducetheup-to-date nomen-claturefor pediatric urinary incontinence after which a general frameworktoguidethepractitionerinclassifying,evaluating,and managinganincontinentchildisprovided.Adetaileddiscussion ofthepathologicprocessesandlong-termmanagementofspecific conditionscausingincontinenceisoutsidethescopeofthisreview.
Definitionsandclassification
Urinary incontinence (UI) is any involuntary or uncontrollable leakageofurine[1].Asurinaryincontinencecanbepresentina varietyofsituations,theInternationalChildren’sContinence Soci-ety(ICCS)hasunifiedthedefinitionsandterminologyofpediatric urinaryincontinenceandlowerurinarytractsymptoms[1]. Con-tinuousincontinencerefersto constantleakageofurineand can occurevenininfantsandyoungchildren.Intermittentincontinence
isdefinedasany urineleakagein discreteamountsin achildat least5yearsold.Whenachildhasneverbeendryofurine,they haveprimaryincontinence.However,ifachildbecomes inconti-nent aftera previous period of good urinarycontrol, theyhave
secondary incontinence. When intermittent incontinence occurs whilethe childisawake, itiscalleddaytimeincontinence. Con-versely,whenoccurringwhileasleepitisdescribedasenuresisor
nocturnalenuresis,whicharesynonymousterms.Whenenuresis occursinisolation,thatiswhenthereisnohistoryoflowerurinary tractsymptoms(exceptnocturia),itisdefinedasmonosymptomatic nocturnalenuresis (MNE).Childrenwithenuresisandany other lowerurinarytractsymptoms(LUTS)aredefinedashaving non-monosymptomaticnocturnalenuresis(NMNE).TheseLUTScan bedaytimeincontinence,urgency,frequency,dysuria/stranguria,or others.Whenbedwettingoccursinachildwithconcomitantdaytime lowerurinarytractsymptomscausingincontinence,thechildhasa dualdiagnosisofnocturnalenuresiswithdaytimeurinary inconti-nence.Urgeincontinencereferstourinaryleakageresultingfrom urgency.Giggleincontinenceisanunusualphenomenonmostoften foundingirlsinwhichnearlycompletevoidingoccursduringor immediatelyafterlaughing.Theuseofterms‘totalincontinence’ and‘diurnalenuresis’isdiscouraged.Theformertermisreplacedby continuousincontinence,whereaschildrenwithbothdaytimeand nighttimeincontinence,formerly describedas ‘diurnalenuresis’, haveadualdiagnosis–daytimeincontinenceandnocturnalenuresis. Neurologicallyintactchildrenwithurodynamicallyproven inter-mittentvoluntarycontractionsoftheexternalurethralsphincteror pelvicfloorduringvoidingaresaidtohavedysfunctionalvoiding.
Childrenwithurinaryincontinencewillbefound tohaveoneof threeetiologiesfortheirincontinence(Table1).Anatomiclesions canleadtocontinuousincontinence,avitalcluethatcanbeelicited fromthehistoryandexamination.Infemales,ectopicureterswith orificesdistaltotheexternalurinarysphincterwillcause continu-ousincontinence,asdothesphinctericdeficienciesseeninchildren withepispadias,bladderandcloacalexstrophy.Treatmentforother congenitalurinarytractanomaliessuchasposteriorurethralvalves andectopicureterocelescandamagethenormalsphinctercontrol mechanismsandsecondarilycauseurinaryincontinence.
Neurologiclesionsinthebrain,spinalcord,orautonomicand/or somaticperipheralnervoussystem(s)canresultin incontinence. The most common cause of neurogenic bladder dysfunction in
Table1 Generalclassificationofurinaryincontinence.
Anatomic Congenital Ectopicureter
Bladderexstrophy-epispadiascomplex
Persistenturogenitalsinuswithhighgenitourinary confluence
Urethralduplication Acquired
Iatrogenicinjurytoexternalurethralsphincter(e.g. afterposteriorurethralvalveablationorectopic ureteroceleexcision)
Neurologic Congenital Myelodysplasia Occultspinaldysraphisms Sacralagenesis
Acquired
Centralnervoussystemlesion(e.g.cerebralpalsy, tumor,radiation,stroke,multiplesclerosis) Peripheralnervoussysteminjury(e.g.injuryto pelvicplexusandbladderefferents/afferents) Functional Daytimeincontinence
NocturnalEnuresis
children is myelodysplasia [2], aterm usedto describe various abnormalitiesresultingfromfailedfusionofthevertebralcolumn with associated malformations of the spinal cordand surround-ingstructures.Morespecifically,myelodysplasticpatientscanhave a protrusion of the meninges with intact spinal cord elements (meningocele),protrusionofspinalcordelementswiththemeninges (myelomeninogocele),orevaginationoffat,meninges,andspinal cordelements(lipomyelomeningocele).Occultspinaldysraphisms areconditionssuchasfattyfilumterminale,intramedullarylipoma, neurenteric cysts, terminal syringohydromyelia with subtle skin defectsandphysicalfindingslikemidlinenevi,hemangioma,lower midlinehairypatch,oranassymetricglutealcleftthatcansuggest atehteredspinalcordasacauseforurinaryincontinence.Occult spinaldysraphismsaredistinctfromspinabifidaocculta,whichis themildesttypeofvertebralbonydefectinwhichthesacrumhas failedtofuseinthemidlinebutdoesnotinvolvethespinalcordor dura.Spinabifidaoccultaisanincidentalfindingaspatientshave nosymptoms.
Whilespinaldysraphismsmaybethemostcommoncauseof neu-rogenicpediatricurinaryincontinence,anyacquiredconditionthat interruptsthenormalcorticalcontrolmechanism,spinalpathways, orbladderefferentsandafferentscanresultinneurogenicurinary incontinence.Theconditionsthatcausethisarewideandvaried, butsomeexamplesinclude:hypoxicinsultslikecerebralpalsyor pediatric strokes affecting the brainstem or higher urinary con-trol centers, brainor spinal cord tumors that primarily or as a resultoftheirtreatmentresultinincontinence,andradicalpelvic surgeryforcongenitalanomalies(e.g.a‘pull-thru’operationfor imperforateanus)orcancers(e.g.aradicalpelvicexenterationfor rhabdomyosarcoma)thatdamageperipheralautonomicorsomatic nervesandsacrificecontinence.
Finally,functionalincontinencecanoccurinchildrenwithoutany knownanatomicorstructuralneurologiclesions.Theetiologyof daytimeincontinenceandnocturnalenuresisisvaried.Urinarytract infectionscancauseinflammationandirritationthatleadto tran-sientincontinence.Childrencanhavebehavioralissuessuchasurine
holdingthatleadstodetrusoroveractivityand/oroverflow inconti-nence.Detrusoroveractivityhasalsobeenimplicatedinnocturnal enuresis,ashavelowerthannormallevelsofnocturnalvasopressin secretionandimpairedsleeparousalpatterns[3–5]. Mood disor-derssuchasattentiondeficithyperactivitydisorderandanxietyas wellasconductdisordersarefrequentcomorbiditiesencounteredin childrenwithUI[6–8],asisconstipation[9,10].Previously conti-nentchildrenexperiencingastressfullifeeventsuchasthedivorce ofparentsorlossofasiblingcandevelopsecondaryincontinence [11,12].
Epidemiology
Pediatric urinary incontinence is a common disorder affecting children of all ages and cultures. Unfortunately due to their population-basednature,moststudiesaddressingtheprevalenceof pediatricUIdonotclassifybytheetiologyofincontinence,yetthey arestillhelpfulinunderstandingtheprevalenceofurinary inconti-nenceingeneral.Asampleof1192threetotwelveyearoldchildren fromtheUnitedStatesidentifieddaytimeincontinencein10%of children[13]. Kajiwaraidentified daytimeincontinence in 6.3% ofseventotwelveyearoldJapaneseprimaryschoolchildrenand affectedmalesandfemalesequally[14].Sureshkumarperformeda populationbasedsurveyandfoundthat19.2%ofschoolage chil-drenhad experienceddaytime UI atleastonce in the 6months priortosurvey,withahigherprevalenceinfemalesthanmales[15]. AnotherAustralianstudyoffivetotwelveyearoldschoolchildren identifiedaprevalenceof2%forisolateddaytimeUIand4%for daytimeincontinenceandnocturnalenuresis[16].Similarly,6%of schoolagegirlsand3.8%ofschoolageboyshaddaytimeUIinone Swedishstudy[17].
Enuresisisalsohighlyprevalent.Inastudyof10,960childreninthe UnitedStates,nocturnalenuresiswasfoundinboysatsevenandten yearswas9%and7%,respectively,andingirlsatthoseageswas 6%and3%[18].Bloomidentifiedenuresisin18%ofanotherUS sample,thoughthemedianagewaslower[13].Alargepopulation basedstudyinGreatBritainsuggestedthat20%ofchildreninthe firstgradeoccasionallywetthebed[19].Giventheprevalenceof pediatricUIandassociatedsymptoms,itisnotsurprisingthatit represents7%and40%ofgeneralpediatricoutpatientreferralsand pediatricurologyvisits,respectively[20,21].
Asmentioned,nopopulation-basedstudiesinvestigatingthe preva-lenceofpediatricUIdosobytheirspecificetiologies.Itisreasonable to concludefrom clinical experience and from the relative rar-ityofanatomicandneurologiccausesthatthelargestproportions ofchildrenwithurinaryincontinencedonothaveorganiccauses. Nevertheless,itisalwaysprudenttoconsidertheseetiologiesinthe initialevaluation andsubsequentmanagementof theincontinent child.
Evaluation
Adetailedhistoryandphysicalexamarethe cornerstonesofthe evaluationofpediatricurinaryincontinenceandguidewhichtests, ifany,shouldbeconsidered.Table2showsthe evaluationtools availabletotheclinicianfacedwithanincontinentchild.
Thehistoryshouldbebroadyetspecificandincludeinformation fromthechildaswellasthecaregiver/parent.Detailedinformation
regarding when(daytime or nighttime), where (at school/public placeand/orathome),howoften(onceaweekordaily),andhow much(smallor largevolume)leakage occursisimportant,asis informationpertainingtobowelhabits,withadeterminationofthe frequencyandconsistencyofbowelmovementsandpresenceofany bowelaccidents.Frequency-volumecharts(i.e.voidingdiaries)can behelpfulingatheringthisinformationaboutvoidingand elimina-tionhabits.Theprovidershouldidentifyifthechildhashadany previousoperationsincludingbutnotlimitedtoabdominal, gen-itourinary,and pelvicsurgery.Knowing whether therewas ever aperiod of complete urinary controlin achild of toilet-trained agecanhelpdistinguishbetweenprimaryandsecondary inconti-nence.Detailsoftheperinatalhistoryareimportant,asarequestions focusedonthechild’sgrossandfinemotorandbehavioral devel-opment.Motorimpairmentscouldsuggestunderlyingspinalcord pathologyalsoaffectingthelowerurinarytract.Schoolperformance andbehaviorshouldbequeried.Asattentiondeficithyperactivity disorderhasbeenassociatedwithurinaryincontinence,oneshould askwhethertheteacherhasnotedthechildtobeeasilydistractedor hasproblemswithimpulsivity.Conversely,highachievingchildren whoareveryfocusedonschoolperformancecanacquirevoiding postponementandurgeincontinenceandshouldthusbeidentified. Theprovidershouldquerywhetherthereisanyevidenceofstressors athomesuchasparentalconflictorrecentlossesthatcouldcause developmentalregressionandsecondaryincontinence.Importantly, informationshouldbeobtainedregardinganyhistoryofurinarytract infections.
Likeadetailedhistoryaimedatidentifyingcluestowardtheetiology ofachild’sincontinence,afocusedphysicalexamcanshedlighton theetiologyaswellasdirecttesting.Thegrossmotorfunctionofa childcansimplybeobservedashe/shewalksintotheexamination suite.Anabdominalexamassessingforabdominalmasses,astool filledcolon,ordistendedbladdershouldbeperformed.Theintegrity ofthe lowerabdomen and pubicsymphysisshouldbeassessed. Ingirls,thegenitalexamshouldnotethepresenceandrelationof theurethratothevaginalandrectalorifices.Apatulousurethrain agirlwithawidenedpubicdiastasissuggestsfemaleepispadias. Observationofpoolingurineinthevaginalintroitusisanimportant cluethatanectopicuretermightbepresent.Thechild’sbackshould beexamined,withparticularattentionpaidtorecognizingsignsof occultspinaldysraphism(hairytufts,subcutaneouslipomas,skin discoloration,orsacraldimplesabovetheglutealcleft)andtethered cord(asymmetricglutealfold).Theneurologicalexamshouldassess lowerextremityreflexes,perinealsensation,analtoneandreflex,and thepresenceofthebulbocavernosusreflex.
Thehistoryandphysicalexamwillprovideimportantcluesasto whichadditionaltestswillhelpfurtheridentifythecauseofurinary incontinence.Aurinalysisshouldbeperformedinmostcases,as infection(bacteriuria,pyuria,hematuria),renaldamagewithhigh urineoutput(proteinuria,lowspecificgravity),ordiabetes (gluco-suria)asacauseforosmoticdiuresiscanbeidentified.Aneasy testtoaddtoanyphysicalexamthatgivesimportantinformation regardingbladderemptyingisabladderscanwithpostvoidresidual (PVR)measurement.Thiswillaidtheproviderinknowinghowwell thechildempties,andcanpromptfurtherstudieswhenlargePVRs arefoundonsuccessivetests.Mostchildrenshouldbeabletoempty to5cm3orless,whereasrepeatedresidualmeasurementsof20cm3 ormoreareconcerningforpathologyinthebladderand/orurethra [1].Whendiscovered,highPVRscouldrequirerenalandbladder ultrasound,voidingcystourethrogram,and/orurodynamicstudies
4 A.J. Schaef fer , D.A. Diamond
Table2 Diagnosticoptionsandtheirindicationsintheworkupofpediatricurinaryincontinence.
Diagnosticoption Indications Comments Findings
History •Allpatients •Helpsguidepractionertowardsneurogentic,
anatomic,orfunctionalincontinence
Physicalexam •Allpatients •Helpsguidepractionertowardsneurogentic,
anatomic,orfunctionalincontinence
Urinalysis •Allpatients •Bacteruria/pyuria:infection
•Proteinuria:kidneydamagewithpossiblehighurineoutput
•Glucosuria:diabetesmellituswithpossibleosmoticdiuresis
Bladderscanwithpostvoid residual(PVR)measurement
•Allpatients •NotnecessaryifplanningtoorderRBUS •PVRconsistently>20mlonseveralmeasuresneedsworkup toidentifyifneurogenic,myogenic,oranatomiccauseis present
Uroflowmetry •Mostpatients •CanincludeEMGiffullurodynamicsnotplanned SeeFig.1
Renalandbladderultrasound (RBUS)
•Mostpatients •Providesfunctionalinformation(estimatedbladder
capacity,bladderemptying/postvoidresidual,bladder wallthickness)
•Identifiesgrossupperandlowerurinarytractpathology
•Identifiesconstipation
•Renalscarringsuggestsvesicoureteralreflux(VUR)
•Dilatationofureterandduplicateduppertractsuggestiveof ectopicureter
•Thickenedbladderindicateshighvoidingpressuresfrom distalobstruction(anatomic–PUV;neurologic– detrusor-sphincterdyssynergia)
Abdominalradiography •Mostpatients •Identifiesgrossbonyanomalies
•Identifiesconstipation
Urodynamics •Failedmedicalorbehavioraltherapy
•Suspectedneurogenicpathology
•Storagemeasurementsinclude:maximumbladder capacity,Pdetatbladdercapacity,detrusorleakpoint
pressure,abdominalleakpointpressure,bladder compliance,detrusoroveractivity
•Emptyingmeasurementsinclude:uroflowmetrywith EMG,maximalPdetduringvoid,voidedvolume,PVR
•Identifiesneurologicetiology
•Providesevidencetoguidetreatment
Spinalultrasound •Suspectedspinalpathology •Applicableinthose<6monthsofage •Identifiesspinaldysraphisms,tetheredspinalcords,andother occultspinallesionsassociatedwithneurogenicincontinence
SpinalMRI •Suspectedspinalpathology •Applicableinthose>6monthsofage
•Requiressedationinmanychildren
•Identifiesspinaldysraphisms,tetheredspinalcords,andother occultspinallesionsassociatedwithneurogenicincontinence
VCUG •Post-UTI
•Suspectedanatomicabnormality(e.g.ureterocele, ectopicureter,duplicatedurethra)
•Adolescentmaleswithincontinence
•Identifiesposteriorurethralvalves
•Identifiesectopicureterswithorificesatexternalurethral sphincter
•‘Spinningtop’urethraindicativeofdysfunctionalvoiding
Magneticresonanceimaging (MRI)/urography(MRU)
•Suspectedanatomicpathology(e.g.ectopicureter) •Requiressedation •Clarifiesanatomyofectopicuretersandtheirrenal component,Müllerianremnants,andotherunusualanatomic abnormalities
Cystoscopy •Rarelyusedindiagnosisofincontinence
•Appropriatewhenotherdiagnosticmodalities havenotprovidedetiologyofincontinence
F
EMG Flow Rate m l/s μV 5 10 15 25 20 seconds secondsG
μV EMG m l/s Flow Rate >6 sec 5 10 15 25 20 Flow Rate ml/ s μVE
5 10 15 25 20 EMG seconds EMGA
C
EMG Flow Rate ml/ s μV 5 10 15 25 20 seconds seconds 5 10 15 25 20 m l/s μV m l/s μV EMG seconds Flow Rate 5 10 15 25 20 seconds Flow Rate m l/s μVD
5 10 15 25 20 EMGB
Flow RateFig.1 Examplesofuroflowmetryinchildren.(A)Normalflowshowingbell-shapedcurveandcessationofexternalsphincteractivityonEMG. (BandC)Staccatoshapedflow,whichcanoccurwithaweakorunsustaineddetrusorcontractionbutquietexternalurethralsphincter(asinB)or withperiodicburstsofsphincteractivityonEMGwhilevoidingwithacontinuousbutvaryingflowrate(asinC).ToqualifyasaStaccatopattern, thefluctuationsinflowshouldbelargerthanthesquarerootofthemaximalflowrate.(D)Interruptedorfractionatedvoidingnotableforperiodsof nourineflowintheabsenceofEMGactivity.LiketheStaccatopattern,thiscanoccurwithanunsustaineddetrusorcontractionbutalsoresultwhen voidingisachievedviaabdominalmusclecontractionsinthepresenceofanacontractilebladder.(E)Plateaushapedflowshowinglowamplitude, prolongedvoidandcessationofsphincteractivityonEMG.Thisoccursasaresultofafixedanatomicobstructionoraweakdetrusorcontraction. Plateaushapedflowcanalsooccurwithatonicallyactiveexternalsphincter(notdepicted).(F)Towershapedflowwithahighamplitude,short durationofflowcausedbydetrusoroveractivity;mayresultinurgeincontinence.(G)Primarybladderneckdysfunctionwithurineflowbeginning atleast6safterthecessationofsphincteractivityonEMG.
6 A.J.Schaeffer,D.A.Diamond toelucidateifthehighresidualisfromananatomic,neurologic,or
functionalcause.
Similarly, a uroflow with external sphincter electromyography (EMG)isa testthatcaneasily bedone inthe clinician’s office thatcanprovidecluesastothecoordinationofpelvicfloorduring micturition.ThedecisiontoexcludeEMGfromtheuroflowcanbe madeifafullurodynamicstudy(whichincludesexternal sphinc-terEMG)isgoingtobeperformed.TheEMG,whetherobtained duringuroflowmetryoraurodynamicstudy,providescritical addi-tionalinformationthatcanpreventincorrectdiagnoses[22].The childshouldbeinstructedtodrinkfluidinanamountequaltotheir estimatedbladdercapacity60minpriortothetest.Also,twotests (eachwithavoidedvolumebetween50%and100%ofestimated bladdercapacity)shouldideallybeperformedtoaccountfor vari-abilitybetweencurvesgeneratedfromthesameindividuals.Asthere arenopediatricspecificstandardizedflowrates,thepatternofthe flowcurveisusedto distinguishpathologicfromnon-pathologic emptying.Anormalflowcurveshouldbebell-shaped(Fig.1).A staccato-likeuroflowhaspeaksandtroughsbutacontinuousurinary stream.Thiscanoccurwithaweakorunsustaineddetrusor contrac-tioninthepresenceofaquietEMGorwithanadequatedetrusor contractingagainstanactiveexternalsphincter,asseenin dysfunc-tionalvoiding.Aninterruptedflowcurve(fractionatedvoiding)has periodsofzeroflowintheabsenceofEMGactivity,andcanoccur withanunsustaineddetrusorcontractionorresultwhenvoidingis achievedviaabdominalmusclecontractionsinthepresenceofan acontractilebladder. Aflat,plateau-likeflowcurveissuggestive ofeitherafixedanatomicobstruction,aweakbladdercontraction (fromeitheraneurogenicormyogeniccause),oratonicallyactive externalsphincter.Ahighamplitude,shortduration“tower-shaped” flowcurveissuggestiveofdetrusoroveractivitypotentially result-ingin urgeincontinence.Glassberghas useduroflowandEMG to detectprimarybladder neck dysfunctionin those who’stime betweenpelvicfloorrelaxationandtheinitiationofurineflow(EMG lagtime)wasgreaterthan6s[23].
Therenalandbladderultrasoundshouldbeconsideredan appro-priatenon-invasivetestinmostchildrenwithurinaryincontinence. Theultrasoundshouldbedetailedenoughtodeterminethepresence orabsenceofduplicatedrenalcollectingsystem,renalmorphology andscarring,uppertractdilatation,bladdercapacity,andbladder wallthickeningorirregularity.Boththe upperandlowerurinary tractsshouldbeimagedwithafullandemptybladder.Aplainfilm oftheabdomenshouldbeconsideredinmostcasesaswell,with particularattentiondirectedtowardsidentifyingtheamountofstool inthecolon,andthepresenceofanyvertebralbonyanomalies (pos-siblyindicatinganeurogeniccauseofurinaryincontinence)and/or awidenedpubicdiastasis(possiblyindicatingadisorderalongthe epispadias-exstrophyspectrum).
Urodynamicswithexternalurethralsphincterelectromyographyare indicatedforthosewithasuspectedor provenneurologiclesion (tetheredcordonMRI,allpatientswithspinabifida,patientswho havehadradicalabdominopelvicsurgery),incontinentadolescent maleswithlatediagnosisofposteriorurethralvalves,andinpatients whofailbehavioralormedicaltherapy.Thespecificsofthe urody-namicsstudyaredescribedindetailbyMacLellenandBauer[2]. Briefly,thetestincludesan11Frtriplelumenurodynamiccatheterin thebladdertomeasureintravesicalpressure(Pves),asmallballoon catheterintherectumtomeasureintrabdominalpressure(Pabd),and eithera24-gaugeneedleelectrodeplacedintotheskeletalmuscle
oftheexternalurethralsphincter[24]orperinealpatchelectrodes [25]to measureexternalurethralsphincter activity.Thedetrusor pressure(Pdet) iscalculatedbysubtractingPabd fromPves. These measuringdevices areconnectedto commerciallyavailable uro-dynamicsystemsto recordanddisplaythe measurements.Upon insertingtheurethralcatheter,thebladderpressureshouldbenoted. TheinitialvoidingopportunityallowsuroflowmetrywithEMG,the detrusorandabdominalpressuresduringvoiding,andthevoided andresidualurinevolumetobemeasured.Thebladderisthenfilled withwarmed37degreesaline atarateequaltoone-tenthofthe child’spredictedorknown capacity(capacity/10). Key measure-mentstakenduringbladderfillingandstorageincludethemaximal bladdercapacityanditsassociateddetrusorpressure,detrusorleak pointpressure,presenceofdetrusoroveractivity,whetherleakage occurswiththe increasedabdominalpressure,andthevolumeat firstleak.Theinstillationofradiopaquecontrastmediuminstead ofsalinetogetherwithfluoroscopicequipmentenables videourody-namics,orreal-timevisualizationofthebladderneckandurethra duringthevoidingphase,tobeperformed.
Severalotheradjunctivetestscanplaykeydiagnosticroleswhen indicated.If the history and/orphysical investigationssuggest a neurologic etiology, the spinal cord should be imaged to iden-tifyanomaliessuchassyringocele,cordtethering,ormalposition, amongothers. Ultrasound canbe usedin those younger than 6 monthsofage,owingtothefactthatthevertebraearenotcompletely ossified.Inthoseolderthan6monthsofage,MRIisindicatedto detectvertebralandspinalcordpathology.Amagneticresonance urographycanbeperformedwhenthereisasuspicionofortohelp definetheanatomyofanectopicureterorotheranatomiccauseof incontinencesuchascommoncloaca,urogenitalsinus,oranorectal anomalies.Avoidingcystourethrogram(VCUG)shouldbe con-sideredinincontinentchildrenwithahistoryoffebrileUTIandin adolescentmaleswithUI.Intheformer,unlessanobstructedectopic ureterisfoundtobeenteringintotheexternalurethralsphincterin girls,theVCUGisnotlikelytodiagnosethecauseoftheurinary incontinence(which could befrom the infectionand inflamma-tioncausingtemporaryirritationtothebladder),butisimportant toruleoutvesicoureteralrefluxandothersinisterfindings. How-ever,asmallproportionofmaleswithposteriorurethralvalveswill presentinadolescence(owingtolessseverediseaseorlackof prena-talcare),inwhichcasetheVCUGisdiagnostic.Finally,indifficult casesofincontinence,acystoscopy canidentifywhetherthereis urethral(suchasadiverticulum,urethralduplication,orlarge pros-taticutricleallwhichwouldleadtopost-voiddribbling),bladder neck,orbladderpathology.
Questionnairesdevelopedtoassessincontinence
Standardizedpediatricincontinenceassessmenttoolsnicely com-plementthephysician’shistoryandphysicalexam.Thesetoolsare designedtobefilledoutbythechildorparent/caregiverasproxy andcanbeusedattheinitialintakeaswellasatsubsequentvisitsto helptracksymptomsoverthecourseoftherapy.Someofthesetools assessthesymptomsandseverityoflowerurinarytractsymptoms (LUTS) and urinary incontinence by incorporating urinary fre-quency,urgency,thedegreeofwetness,andcoexistentconstipation orboweldysfunctionintoparent-proxyorchildself-reported instru-ments[26–28].ThePediatricIncontinenceQuestionnaire(PIN-Q) wasdesignedtoascertaintheeffectofincontinenceonachild’s qual-ityoflife[29].TheBristolStoolScalecanbeprovidedtopatients todeterminethequalityandcharacteroftheirbowelmovements
[30]. Thereisgreatoverlapin urinarysymptomsmeasuredwith theseinstruments,andnoonequestionnairehasbeenfoundtobe superiortoanother,suchthattheclinicianshoulddecidewhichone (ortwo)instrument(s)capturesthesymptomstheydesirewhilealso minimizingpatientburden.Also,itisimportanttodetermineifthe selectedquestionnairehasbeenvalidatedwithinaparticular cul-tural,social,andlanguagecontext.Simpleverbatimtranslationofa questionnaireintoanotherlanguageisdiscouraged,asthemeaning ofparticularquestionscanbeskewedbecausetheculturalcontextin whichthesurveywasdesignedmaydifferfromthatoftheintended environment.
Management
Athoroughhistory and physicalexamwith the additionof fur-therdiagnostic tests,whereindicated,willhelp determineifthe primaryetiologyisfunctional,neurologic,oranatomic.The man-agementisthentailoredtoeachtypeofincontinence,withsome overlapinmedicationsandtherapiesbetweentheformertwotypes ofincontinence.
Functionalincontinence a.Daytimeincontinence
It is important to emphasizeto parentsand children that many patientswithoccasionaldaytimeincontinenceorenuresiswillfall withinthenormaldevelopmentalspectrum,andthattheircondition isexpectedtoimproveovertime.Nevertheless,owinginparttothe resultantpsychosocial distress andfamilyburden, manypatients andfamilieswillappropriatelydesiretreatment.
As constipation is highly prevalent in this population [9], and becauseitstreatmenthasbeenshowntoimprovecontinence[31], bowelmanagementisamajorpriorityinthemanagementof chil-drenwithdaytimeincontinence,enuresis,anddysfunctionalvoiding or dysfunctional elimination syndrome. Althoughthe findingof stoolonabdominalfilmisindicativeofconstipation,thecorrelation betweentheradiographicfindingsofstoolandthedegreeof consti-pationisweak.Nevertheless,theradiographicfindingofmorethan normalamountsofstoolinthecolonshouldprovidestrongenough evidencetoconvinceparentswhoinsistthattheirchildhas‘normal’ bowelmovements.
Abehavioralapproachtobowelmanagementisthefirststep.After ensuringthatthechildisingestingappropriateamountsoffiberand drinkingenoughfluid,thisapproachconsistsoftwoormoredaily attemptsatbowelmovements.Thechildshouldsitonthetoiletfor atleast5min,evenwhenevacuationattemptsareunsuccessful.If theseconservativemeasuresfailtoshowimprovement,theaddition ofpolyethyleneglycol3350(MiraLaxTM,GlycoLax)isoften suc-cessful.Therecommendeddosesforconstipationare0.5–1.5g/kg dailytitratedtoeffect,withamaximaldoseof17g/day.However, childrencangenerallytolerateandmayrequiremuchmorethanthis. Thus,34–51g(twotothreecapfuls)oncedailydissolvedin240mL ofwaterorjuicewithasennosidesorallaxativeonceaweekcan beusedforseveralmonths.Downtitrationbeginsapproximately sixmonthslaterafterconsistentlysofterstools,moreregularbowel movements,andimprovementsonabdominalradiographarenoted. Somepatientswillrequireamoreaggressivebowelcleanoutwhich utilizesalargedose(twoof moreliters) ofpolyethylene glycol 3350withbalancedelectrolytes(GoLytely®)givenover2or3days,
withorwithoutdigitalorpharmacologic(bisacodyl,glycerin)rectal stimulation.
Themanagementofthebladdercanbeginafterabowelmanagement program,whenindicated,hasresultedinregularsoftdailybowel movements.Bladdertherapyproceedsinastepwisefashion,and canbesuitedtoparental/caregiverpreferences.Behavioraltherapy isagoodstartingpoint,thehallmarkbeingtheinstitutionofastrict every2–3hdaytimevoidingregimenaftereducatingthechildabout normalbladderfunctionandsensation.Childrenarealsoencouraged toavoidcaffeinated,carbonated,andhighlyacidicfluids.Voiding diariesclarifyforboththefamilyandprovidertheevacuationhabits, andneedtoincludeinformationregardingthetimeandtheamount ofeachvoidand/orleakageepisode,timeandconsistencyofeach bowelmovement,andamountoffluidintake.Aidedbyanormal bladdercyclingregimen,the goalofbehavioraltherapyisto re-educatethechildaboutnormalbladdersensationandgarnercentral controltosuppressbladderurges.
Complementingbehavioraltherapyisbiofeedbacktherapy,which providesvisualandauditoryfeedbacktochildrenabouttheexternal urethralsphincterandpelvicfloorbioactivityduringbladder fill-ingandemptying.Programsandgamesintegratedwithpelvicfloor rehabilitationarethenusedtoteachchildrenhowtorespondto nor-malbladderurgesduringstorageandpromotepelvicfloorrelaxation duringbladderandbowelelimination,thustargetingdetrusor over-activityanddysfunctionalvoiding,respectively.Althoughthereare norandomizedcontrolledtrialsassessingtheefficacyof biofeed-backtherapy,oneobservationalstudyshowedimprovementin89% and 90% of children with daytime incontinence and nocturnal enuresis[32]. Constipationwasimprovedin 100%and resolved completelyin33%.Biofeedbacktherapyisundertakenover sev-eral sessions, with specialists in pediatric urology coaching the patientsthroughtheprocess.Thisoptionrequiresthecommitment offamiliestoattendseveralsessionsandanattentiveandmotivated child.
Whilebehavioralandbiofeedbacktherapyaregoodnon-invasive, non-pharmacologicmethodsto treaturinary incontinence, phar-macologic therapy plays an important role in pediatric voiding dysfunction,particularlyamongpatientswhodonotrespondtoor cannotparticipateinmoreconservativeapproaches.
Oralanticholinergictherapyisusedforthetreatmentofoveractive bladderand urge incontinence(Table3). Althoughseveral anti-cholinergicsareusedoff-labelinchildrenwithUI,onlyoxybutynin isapprovedby theUnitedStatesFood andDrugAdministration (FDA)foruseinthispopulation.BothM2andM3muscarinic recep-torsarefoundinthebladder,buttheM3subtype’sstimulationresults indirectdetrusorcontractionandmicturition[33].Inblockingthese receptors,anticholinergicsmitigatetheimpactofuninhibited blad-dercontractionsandincreasebladdercapacity,therebydecreasing incontinenceepisodesand increasing the timebetweenand vol-umeofeachvoidingepisode. Thesideeffectsofanticholinergic drugsincludedrymouth,blurredvision,facialflushing,headache, tiredness,gastrointestinaldiscomfort,andconstipation.Thedegree towhichthesesideeffectsareapparentdependsonthespecificity ofthe selectedanticholinergic.Oxybutyninisknowntodecrease sweating, thus causing heat intolerance and overheating during thesummer as wellas preventing someathletes from tolerating thisdrugwhileengagedinsport.Althoughnoshorttermmemory deficitswerefound inchildren takingoral anticholinergics[34],
8 A.J.Schaeffer,D.A.Diamond Table3 Commonlyusedmedicationstotreatpediatricurinaryincontinence.
Medication Dosage Indicationandnotes
Anticholinergics •Urgeincontinencefromdetrusoroveractivity
Oxybutynin(Ditropan) 0.2mg/kgbid–0.2mg/kgqid •Transdermalrouteofadministrationallowsforpost-operativeuse whenawaitingreturnofbowelfunctionandavoidsinitialfirst-pass metabolism,potentiallyreducingsideeffects
•Intravesicaladministrationtoutedtoreducesystemicsideeffects,but noLevelIevidencesupportsthis
•OnlyanticholinergicFDAapprovedforuseinchildren Tolterodine(Detrol)a 0.01mg/kgbid–0.04mg/kgbid
Hyoscyamine(Levsin)a 0.03mg/kgbid–0.1mg/kgtid
Trospium(Sanctura)a 10–20mg/day
Solifenacin(Vesicare)a 5–10mg/day •BetterM3selectivitypurportedlyreducessideeffectscomparedto
oxybutynin,tolterodine,andtrospium
Darifenacin(Enablex)a 7.5–15mg/day •BetterM3selectivitypurportedlyreducessideeffectscomparedto
oxybutynin,tolterodine,andtrospium
Alpha-sympathomimetics •Lowabdominalleakpointpressureorurethralpressureprofile
Ephedrinea 0.5mg/kgbid–1mg/kgtid
Pseudoephedrinea 0.4mg/kgbid–0.9mg/kgtid
Alpha-adrenergicreceptor antagonists
•Primarybladderneckdysfunction
Tamsulosin(Flomax)a 0.4mg/day
Doxazosin(Cardura)a 0.5mg-2mg/day
Alfuzosin(Uroxatral)a 10mg/day
Terazosin(Hytrin)a 1–20mg/day
Antidiuretics •Enuresis
Desmopressin 0.2–0.4mg/night •Controlsbutdoesnotcureenuresis
•Comparedtoimipramine:nodifferenceinefficacy,moreexpensive, noanticholinergicsideeffects
•Intranasalformulationnotapprovedforenuresis
Tricyclicantidepressants •Enuresis
Imipramine 25–50mg/night •Controlsbutdoesnotcureenuresis
•Comparedtodesmopressin:nodifferenceinefficacy,cheaper,higher sideeffectprofile
Neurolytics •Neurogenicandnon-neurogenicdetrusoroveractivityinpatientsnot
respondingtoconventionaltherapy Onabotulinumtoxin–TypeA
(Botox)a
10–12IU/kgdilutedin30ml normalsaline,max300IU
•App.30trigone-sparingsubmucosalinjections(1mleach)under cystoscopicguidance
•Repeatinjectionsneededafter3–12monthstosustaineffect a NotFDAapprovedforLUTuseinchildren;optimaldoseinformationlacking.
onestudynotedhyperactivity,insomnia,andagoraphobiaina neu-rogenicpopulationbeingadministeredintravesicaloxybutynin[35]. Patientswithconcomitantconstipationshouldbethoroughly evacu-atedandmaintainedonaneffectivebowelregimenbeforeinitiating anticholinergictherapy.
Therearefewrandomizedcontrolledtrialsassessingtheefficacy oforalanticholinergicsinchildrenwithdaytimeincontinence.One studycomparedoxybutynintobiofeedbacktherapyandplacebo, andfoundnodifferenceinthenumberofincontinentepisodesafter ninemonthsoffollow-up[36].EvenwiththepaucityofLevel1 evidencedemonstratingtheirefficacy,theapparentclinical effec-tivenessoforalanticholinergicssupporttheiruseinthispopulation. Otheroralpharmacotherapiescanbeselectedbasedonspecific eti-ologiesof daytime incontinence. Alphasympathomimetics such asephedrineorpseudoepherinecanbeusedtotargetthebladder neckandexternalurethralsphincterinpatientswithlowabdominal leakpointpressuresandintrinsicsphincterdeficiency,thoughthis
approachhasnotbeenrigorouslystudied.Alpha-adrenergic recep-torantagonists,firstdescribedby Austinand colleaguesin1999 [37],canbeselectedforyoungmalesfelttohaveurinary incon-tinencethat resultsforprimarybladderneck dysfunction.These individuals haveimpairedrelaxationofthe bladderoutletwhich isevidencedbyadelayoflongerthan6secondsbetweenexternal sphincterrelaxationandtheinitialurineflowasseenon uroflowme-trywithEMG[23].Asthesemedicationsareusedoff-labelforthis indication,thereislimiteddataregardingtheiroptimaldosesand sideeffectprofilesinchildren.However,onerecentstudyfoundno adversebloodpressureeffectsinchildrengiventamsulosininadult doses[38].Itisrecommendedtostartpatientsatthelowestadult doseforaparticularagent,withtitrationasneeded.Several obser-vationalstudieshaveshownimprovementsinPVR,uroflowmetry, and/orEMGlagtimewithalphablockertreatment[23,38,39].The onerandomizedcontrolledtrialofdoxazosinversusplacebofound nodifferenceinPVRoruroflowmeasurements,althoughthestudy designdidnotcallfordoseescalationandthestudymayhavebeen toosmalltodetectadifferenceinefficacy[40].
Intravesicalonabotulinumtoxin–A(BTX-A,Botox)hasbeenused off-labelin the treatment of overactivebladder in children with primarilyneurogenicandbutalsonon-neurogenicurinary incon-tinence.Apotentbuttemporaryneurotoxin,botulinumblocksthe releaseofacetylcholinefrompresynapticnerveterminals, preven-tingthestimulationofmuscarinicreceptorsinthedetrusormuscle and subsequent bladder contraction. With cystoscopic guidance undergeneralanesthesia,injections ofa10U/mlsuspensionare placedsubmucosallythroughoutthe bladder,sparingthetrigone. ThismedicationisnotFDA-approvedforuseinchildren,sodose andefficacydataaresparse.Typically,dosesare10–12U/kgwith amaximaldoseof300U(equatingto30 injectionsof 10U/ml) [41]. The duration of effect ranges from 3 to 12 months, with repeatedinjectionsneededtomaintaintheclinicaleffect[42–44]. Therearenorandomizedcontrolledtrialscomparingthisagentto placeboorotheroraltherapeutics.Hoebekeinjected100Uinto21 neurologicallyintactchildrenresistanttostandardtreatment,and demonstrateda60%completeand20%partialimprovementinurge anddaytimeincontinenceafteroneinjectionamongthe15children withatleast6monthsof follow-up[44].Urinaryretention last-ingfor2weeksandflankpainfromvesicouretericrefluxoccurred in1femaleand1male,respectively.Theadvantageofthis thera-peuticoptionisthedirectactiononthetargetorgan,thusavoiding the systemicside effectsoforal anticholinergic therapysuchas heatintoleranceandconstipation.Thedisadvantagesarethelackof long-termefficacyandrequirementofgeneralanesthesia. Anothernon-pharmacologicapproachtothetreatmentofoveractive bladderisneuromodulation.Althoughthetherapeuticmechanism isnotentirelyunderstood,thestimulationofafferentsacralnerve fibersintheS2-S4regionisbelievedtoinhibitsupraspinally medi-atedsignalsleadingtodetrusoroveractivity[45].Inchildrenwith detrusor overactivity, stimulation of these fibers can occur via transcutaneousor,muchlesscommonly,directstimulationofthe parasacralnerves[46–49].For parasacraltranscutaneous electri-calnervestimulation(TENS),patchelectrodesplacedinthesacral regionareattachedtoafrequencygeneratorwithstimulationapplied for20–120min.Theoptimaltherapyisdifficulttodetermineasthe publishedstudiesshowsignificantvariationinfrequenciesapplied (2–150Hz),theduration(20–120min)andoccurrence(twicedaily toonceperweek)ofeachtherapeuticsession,aswellasthe num-berofmonths(1–6)TENSwasutilized.Nevertheless,47–62%of subjectsreportresolutionoftheirsymptoms[47,50,51].By stim-ulatingaperipheralsensorynervewhoserootsare locatedinthe L4-S3region,posteriortibialnervestimulation(PTNS)isfeltto centrallyinhibitpregangionicbladdermotorneuronsinthesacral spinalcord[52].PTNSusesapulsegeneratortostimulatepatch electrodesplacedsuperiortothemedialmalleolus.Onegroupfound a41%and71%resolutionrateinoveractivebladderand dysfunc-tionalvoiding,whichimprovedsignificantlywithasecondPTNS cycle[53].BarrosocomparedparasacralTENStoPTNS,andfound 70%and9%completeresolutionintheTENSandPTNSgroups, respectively[54].Importantly,themethodologyvariedsignificantly betweenthetwogroups(i.e.stimulationfrequencies,session dura-tion,andnumberoftimesperweekforeachsessionfavoredthe TENSgroup), andtheauthors’conclusionthat parasacralTENS ismoreeffectivemaybeoverstated. Asmanyofthestudies for TENSandPTNSreportonlyresultswhileon therapy,the long-termcureratesforthesemodalitiesarenotwelldescribed.Onestudy suggestedthatasmanyas50%ofpatientswillrequirechronic tran-scutaneoustherapy[53].Whenastimulatorisimplanted,curerates forfullresponseare40%andpartialresponseare33%at2yearsof
follow-up[49].Anotherstudyfoundsignificantimprovementsin healthrelatedqualityoflifescoresafteramedian6-month follow-upafterthepermanentstimulatorwasplaced[46].Insummary,if familiesaremotivated,willingandabletoundergochronictherapy, neuromodulationhasacceptableratesofsymptomaticimprovement forchildrenwithnonneurogenicincontinence.
b.Nocturnalenuresis
Three conditions are felt to contribute to nocturnal enuresis – impairedsleeparousalthreshold,nocturnalpolyuria,anddetrusor overactivity[3–5].This knowledgehelps the practitioner under-standthedifferenttreatmentmodalitiesavailablefortheirenuretic patient.Importantly, experts recognize that asignificant portion ofmonosymptomaticenuresispatientslikelyhaveunderreported orunderdiagnoseddaytime symptoms,thus explainingthe over-lappingtherapeuticefficacyin manypatients.Asthetherapyfor non-monosymptomatic enuresis incorporates strategies used for daytimeincontinenceandmonosympotmaticenuresis,thissection willfocusprimarilyonmonosymptomaticenuresis.
After excluding underlying medical conditions and undertaking an appropriate evaluation to exclude relevant comorbid condi-tions,theICCSrecommendsastepwiseapproachtotreatmentof monosymptomaticenuresis[55].Priortoinstitutingany urother-apy,thepractitionershouldassessandtreatconstipation.Thefamily shouldassessnocturnalurineproductionbyweighingdiapersand measuringvoided volumes during normalfeeding and drinking. Whenpresent,nocturnalpolyuria,definedasurinevolumesgreater than130%ofexpectedbladdercapacityforage[55],canhelpdirect thepractionertowardsdesomopressintherapy.
Whenfirstpresentedwithanenureticpatient,educationand sim-plebehaviormaneuversshouldbeemployed.Patientsandfamilies shouldbeeducatedaboutnormalbladderfunctionandbeinstructed to void regularly throughout the day, immediately before bed-time,andonawakening.Themajorityoffluidintakeshouldoccur throughoutthemorningandafternoonwithminimaldrinkinginthe eveninghours.Othersimplemeasuressuchasrewardsystemsfor drynightscanbeinstituted.Comparedtocontrols,childrenwho underwenttheabovebehavioraltherapieswerefoundtohavefewer wetnightsandlowerrelapserates[56].However,boththeresponse andrelapserateareinferiorcomparedtoenuresisalarmsanddrug therapy.
Alarmtherapyisthemainstayoftreatmentforenuresisin those whodonotrespondtoeducationandsimplebehaviormaneuvers. Placedunderthe bedlinensorappliedtotheundergarments,the alarmsenses wetnessand arousesthe patientwithanaudibleor vibratoryalarm.Anadequateunderstandingofthetechnologyand featuresofthedevicebymotivatedcaregiversisrequiredduringthe 3to6monththerapyperiod.Asystematicreviewof3.257children from56randomizedtrialsfoundthattwo-thirdsofpatientsbecome drywhileusingthealarm,thusmakingitanexcellentfirstline thera-peuticoption[57].Ofthosewhobecomedryontherapy,nearlyhalf willrelapse.Severaloptionsexistforthosethatrelapse,including overlearningandrepeatinganothercourseoftreatment. Overlearn-ingistheprocesswherebynewlydrypatientsaregivenextrafluids priortobedtimewhilestillusingthedevice,andhasbeenshown tolowerrelapserates.Someadvocatethataddingdesmopressinto alarmtherapyimprovesresponseinthosethatfailed,althoughthe dataisconflicting[58,59].
10 A.J.Schaeffer,D.A.Diamond Desmopressin(DDAVP)isavasopressinanaloguewithan
antidi-ureticeffectandrepresentsanothergoodfirstlinetherapyoption. TheICCSsuggestthatthebestcandidatesforthistherapyarethose withnocturnalurineproduction>130%ofexpectedbladder capac-ityforage(nocturnalpolyuria)whoareabletovoidatleast70% oftheirexpectedbladdercapacity[55].Whileactivelytakingthe medication,30and40%ofchildrenareestimatedto befulland partialresponders,respectively,withabout1.3fewerwetnightsper weekexpected[55,60].Formerlyindicatedforprimarynocturnal enuresis,intranasalDDAVPisnolongerrecommendedgiventhe riskofhyponatremia-relatedseizureevents.Tabletsareavailablein 0.2and0.4mgdosesandshouldbegivenatleast1hbefore bed-time.Therearenocleardose-relatedeffects[60].Themedicationis welltoleratedwiththeonlynotablebutsignificantriskbeingwater intoxicationcausinghyponatremiaandseizuresinthosewhoingest excessivefluidpriortobed.Therefore,fluidsshouldberestricted to200ml(6oz)orlessduringtheevening.Astherewasno differ-enceinwetnightsaftercessationoftherapycomparingtreatmentto placebo[60],desmopressindoesnotcureenuresis.However,given thefavorablesideeffectprofileandcostnotwithstanding,the med-icationcanbecontinueduntilshortperiodsofabstinenceshowthe childtobedry.
Ofthetricyclicantidepressants(TCA),imipramineishistorically themostcommonlyusedinenuresistreatment.Inadditionto its peripheralanticholinergiceffects,itactscentrallytoincrease vaso-pressinreleaseandmodifythesleeparousalpattern[61,62].For enuresis,thedoses(givenatbedtime)are25mgforpatientsyounger and50mgforpatientsolderthan9years.Sideeffectsofimipramine includetypicalanticholinergiceffectssuchasdrymouthand con-stipation,andmoodchangesandinsomniahavebeenreportedin childrentakingitforenuresis.Athighdoses,imipramineis car-diotoxic,soitsusein thosewithlongQTsyndromeorafamily historyofsuddencardiacdeathshouldbeavoided.Therapyshould beinterruptedeverythreemonthstoavoidtachyphylaxis.One-fifth ofchildrenbecomedrywhilereceivingTCAtherapyforenuresis, thoughlikedesmopressinallpatientsrelapseaftercessation[63].No evidencefavorsdesmopressincomparedtoTCAs[60].Althoughthe sideeffectprofilefavorsdesmopressin,thelowercostofimipramine maymakeitmoreattractivetosomefamilies.
TheICCSalsorecommendsastepwisestrategy totreatNMNE: addressconstipation,ifpresent;diagnoseandtreatdaytimeLUTS; identifyifcomorbidbehavioraldisordersarepresentandreferfor treatment;applystandard therapy formonosymptomatic noctur-nal enuresis [64]. This strategy recognizes that with successful treatmentof precedingsteps, improvement or cure of nighttime symptomsispossible.Thediagnosticandtreatmentstrategies out-linedforconstipation,daytimeincontinence,andmonosymptomatic nocturnalenuresisshouldbeemployedforpatientssufferingfrom nonmonosymptomaticnocturnalenuresis.
Neurogenicincontinence
Patientswithneurogenicincontinencewillhaveleakageasaresult ofdetrusoroveractivitycausingelevationsinintravesicalpressure abovetheurethraloutletresistance(aso-calleduppermotorneuron lesion)and/orfromanincompetentexternalurethralsphincter(a so-calledlowermotorneuronlesion).Importantly,somechildrenwill befoundtohavebothcausesforincontinence.Thisdetermination ismadethroughafullurodynamicstudywithcystometry.Other importantparametersmeasuredonUDSarethebladdercapacity,
whichmaynotprovideanadequatereservoirforurinestorage,and theintravesicalstoragepressures,whichifhighcanleadtorenal deterioration.Theprinciplesofincontinencetreatmentfor neuro-genicbladderarethesameirrespectiveoftheetiologyofthelesion. Thatis,uppermotorneuronlesionscausingdetrusoroveractivity fromtraumaticspinalcordinjuryormyelodysplasiaaretreatedin thesamemanner.Assuch,thissectionfocusesongeneral strate-giestotreatincontinence.Itdoesnotdiscussspecificetiologiesand recognizesthatlesionsevolveandnewsymptomsinaformerly sta-blepatientshouldpromptrepeaturodynamicstudies.Finally,while themaintenanceoflowintravesicalstoragepressuresisofutmost importanceforrenalpreservation,itwillnotbediscussedhere. Cleanintermittentcatheterization(CIC)enablesefficientand com-plete bladderemptyingin patientswithneurogenicbladder who areunabletospontaneouslyvoidyetsufferfromspontaneous unin-hibitedbladdercontractionscausingincontinence.Thefrequencyof catheterizationcanbeadjustedtomaintaindrynessinthesepatients. FollowingCIC,anticholinergicsarethemainstayofpharmacologic treatmentforneurogenicurinaryincontinencecausedbydetrusor overactivity(Table1).Establishingagoodbowelregimenpriorto institutinganticholinergictherapyisofutmostimportanceinthis populationthatisparticularlysusceptibletoconstipation.The anti-cholinergic doses usedto treat neurogenicincontinencemay be higherthanthoseneededinnon-neurogenicincontinence.Ifpatients donotrespondtoaparticularmedication,itsdosecanbeincreased oranalternativeanticholinergictried.
Onabotulinumtoxin–typeA(BTX-A,Botox) hasbeenusedin patientswithneurogenicbladderwhoareeithernon-compliantwith orresistanttoanticholinergictherapy.Althoughthereareno ran-domized controlledtrialscomparingBTX-Ato placeboorother therapeutics,areviewofsixobservationalstudiesusingBTX-Ain mostlymyelodysplasticpatientsfound65–87%ofpatients becom-ingcompletelydryafterinjections,withsignificantimprovements indetrusorstoragepressuresandbladdercompliance[41].Marte’s morerecentstudypresentedsimilarresults,with81%ofchildren becomingcompletelydrybetweencatheterizations[65].Although nodeathsorsignificantsystemicadverseeffectshavebeennoted whenusingBTX-Aforpediatricurologyindications,patientscan experiencetransienthematuria,UTIs,urinaryretention,orpersistent flankpainfollowinginjections[41,44,65].BTX-Aisatemporary neurolytic:patientswhoinitiallyrespondtotherapywillexperience alossoftherapeuticefficacyandrequirerepeatinjectionsafter3 to12months[42–44,65].ThoughnotFDAapprovedinthe pedi-atricpopulation,BTX-Ahasbeenshowntoimprovebladderstorage characteristicsandimprovecontinenceinpatientswithneurogenic etiologies.
Neurostimulationhasbeenusedwithlimitedsuccessinpatientswith neurogenic incontinence. Capitanucci reported improvementsin LUTSinonly1/7(14%)patientswhocompletedthe12week poste-riortibialnervestimulationcycle.Nopatientswerecured,andmany droppedoutofthestudydue tolackofsubjectiveimprovement. GuysrandomizedchildrenwithNGBtoreceiveeithersacral neu-romodulationorstandardtherapywithanticholinergicandbladder neckbulkingagents[66].Sacralneuromodulationwasperformed inthesamefashionasinadultswithcontinuousstimulationofthe S3nerverootviaanimplantablenervestimulator.At12months compliance,bladderfillingpressures,andpost-voidresidualswere the samebetweenthe twogroups,thoughthe conventional ther-apygrouphad greaterimprovementsinbladder capacityandthe
neuromodulationgrouphadgreaterimprovementsindetrusorleak pointpressures.Xiaodescribedaninvasiveneurosurgicalprocedure inwhichalumbarventralnerveisre-routedtothe sacralnerves toprovideanewskintocentralnervoussystemtobladder path-waythatfacilitatesbladderemptying[67].Twelveof14(86%)of patientswithareflexicNGBhadclinicallysignificantimprovements inbladdercapacityandmaximaldetrusorpressureat12monthsof follow-up.Improvements from hostilebladder dynamicstonear normal urodynamicprofiles were seenin 5 of6 (83%)patients withpreoperativedetrusorhyperreflexiaand/ordetrusor-sphincter dyssynergia.TheresultsofclinicaltrialsinvestigatingtheXiao Pro-cedurein the UnitedStatesare forthcoming,and this procedure shouldbedeemedexperimentaluntiltheseandotherstudiesconfirm thefindingsofXiao.
AlthoughCIC and anticholinergic medications are the mainstay oftreatmentforbladderoveractivityintheneurogenicpopulation, somepatientsonmaximalanticholingergicdoseswillcontinueto havehigh-pressure,smallcapacity,overactivebladderswith result-ing upperurinarytractchanges and persistentincontinence.For suchpatients,bladderaugmentationwithcolon,smallintestine,or, infrequently,gastricsegmentscancreateasafe,lowpressure uri-narystoragereservoir.Resultsfromseveralsingleinstitutionseries withlimitednumbersofpatientsshowsignificantimprovementsin bladdercapacity,detrusorleakpointpressure,andcontinencerates [68,69].Onestudyinvestigatedthehealthrelatedqualityoflifein myelodysplasticpatients,andfoundnoimprovementsinpatients’ qualityoflifeaftersurgerycomparedtobeforesurgery[70].Finally, it is important to recognize that the short- and long-term com-plications ofaugmentation cystoplasty(ileus, bowelobstruction, bladder stone formation, vitamin deficiency, metabolic acidosis leadingtobonedemineralizationanddecreasedlinearbonegrowth, andbladderperforation,amongothers)aresignificantandcanbe life-threatening.
Somechildrenwithneurogenicincontinencewillhavean incom-petentbladderoutlet.Insuchpatients,artificialurinarysphincters (AUS),fascialslings,orbladderneckreconstructionscanbeusedto increaseoutletresistance.Eachoptionhasitsownuniqueattributes. AnAUScanmaintainspontaneousvoidingincertainchildrenand providesufficientoutletresistancetoimproveincontinence.They infrequentlybecomeinfectedorsuffererosionsandaredurablebut canrequiresmallrevisionsurgeriesowingtotheirmechanicalnature [71].Autologousrectusfasciaorsmallintestinalsubmucosa blad-derneckslingsandwrapshavebeensuccessfullyusedinpatients withneurogenicsphinctericincontinence[72,73].Inpatientswith bladderaugmentations,slingsprovidetheadvantageofpreserving theurethraasapop-offmechanismandnegatethecomplexityand lowbutpresentinfectiousriskoftheAUS.However,childrenwith fascialslingsmaynotbeabletospontaneouslyvoid.Several vari-ationsofthebladderneckreconstructionexist,andcommontoall areurethralelongationandrelianceon eitherincreasedmuscular backingortheMitrofanoffprincipletoimprovecontinence.These operationsareseldomusedinthispopulationforseveralreasons: theircreationusespreciousbladdercapacity,catherizationcanbe difficult,andtheyoftendonotprovideadequateincreasesinoutlet resistancesufficientforcontinence.
Anatomicincontinence
Treatinganatomicallyrelatedincontinencewithsurgerycanbeone ofthe mostsatisfyingand challengingoperationsforapediatric
urologist.Althoughathoroughdescriptionoftechniqueisoutside thescopeofthisarticle,webrieflydiscussthesurgicalstrategies usedinsomeoftheseconditions.
Whenanectopicureterissuspectedinafemalewithcontinuous incontinenceandverifiedbyradiologicworkup,surgicaltherapycan provideacure.Ifarenalscanconfirmsapoorlyfunctioningupper polesegmentdrainedbytheectopicureter,apartialnephrectomy withexcisionoftheureterasfardistallyaspossiblewillprovide immediatedryness.Alternatively,ifthefunctioningsegment con-tributessignificantlytorenalfunction,itshouldbepreserved.The presenceorabsenceoflowerpolevesicoureteralreluxwill deter-minethesurgicalapproach.Ifrefluxispresent,acommonsheath ureteralreimplantationisaviableoption.Ifrefluxisabsent,anupper tolowerpoleureteroureterostomyorpyeloureterostomyredirects upperpoleurinedrainageto thenon-refluxinglowerpoleureter, thuscuringcontinuousincontinence.
Childrenwithbladderexstrophyorepispadiaswillrequiresurgery to reconstruct the urethra and bladder neck. Several different techniquesare described,though all have the common goals of preservinguppertract function, providing cosmeticallypleasing andfunctionalexternalgenitalia,andachievingurinarycontinence. Astheinitialbladderclosureoftenfailstoprovideadequate out-letresistance,abladderneckreconstructionisusedtocreateoutlet resistancesufficientforcontinencebutstillallowspontaneous void-ing.
Thereare otherrareetiologiesof anatomicurinaryincontinence suchascloacalanomaliesandurethralduplicationswhichrequire individualizedsurgical approaches.Agoodpreoperativeworkup includingdiagnosticimagingandcystoscopywillhelpdefinethe congenitalanomalyandaidthesurgeoninreconstructingnormal anatomy.
Conclusion
Pediatric urinary incontinence is a common condition. A thor-oughhistoryandsystematicphysicalexamwilldirecttheprovider towardsadjunctivetests,ifrequired.Identificationoftheparents’ motivationandgoalsfortheirchild’streatmentwillhelpthe clini-cianformamanagementplanandsetreasonableexpectations.The identificationandtreatmentofconstipationisofutmostimportance priortobeginningincontinencetherapy.Ifclassifiedashaving day-timeincontinence,astepwiseapproachbeginningwithbehavioral andbiofeedbacktherapypriortoinstitutinganticholinergic medi-cationshouldbefollowed.Anevidence-basedapproachtoenuresis suggeststhatalarmtherapyinahouseholdwithmotivatedcaregivers willprovidedurablecuresinamajorityofchildren.Althoughthe relapserates arehigh forenureticchildren onpharmacotherapy, desmopressinandamitryptylinedecreasewetnightswhenthechild takesthemroutinely,andprovideagoodoptionforspecialevents likevacationsorsleep-overs.Identificationofbladderoveractivity and/orsphinctericdeficiencyhelpsdirectthemanagementplanfor neurogenicincontinence.Theformerisoftensuccessfullytreated withCICandanticholinergictherapy;augmentationcystoplastyis reservedforpatientswithhighbladderstoragepressuresand rela-tivelysmallbladdercapacitieswhocontinuetoleakdespitemaximal doseanticholinergics.Surgerytoincreasebladderoutletresistanceis usedtotreatthelatterpatientswithsphinctericdeficiency.Surgeryis alsothemainstayoftreatmentforthosechildrenwithawell-defined anatomicetiologyfortheirincontinence.
12 A.J.Schaeffer,D.A.Diamond Conflictofinterest
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