Ellen Shapiro, MD, FACS
Daniel A. Wollin, MD
BASICS
DESCRIPTION
• Terminology based on 2006 (International Children’s Continence Society) ICCS standards (1)
– Enuresis is intermittent incontinence of urine while sleeping usually referred to as nocturnal enuresis (NE).
– This term is used with or without daytime incontinence or other lower urinary tract symptoms (LUTSs)
• Monosymptomatic enuresis (MNE) is nocturnal incontinence without other LUTSs
– MNE is abnormal in children ≥5 yr of age
• Non-NMNE may coexist with increased/decreased voiding frequency, daytime incontinence, urgency, hesitancy, straining, a weak stream, intermittency, holding maneuvers, a feeling of incomplete emptying, post-void dribble and genital/LUT pain
• Primary enuresis if the child has been dry for <6 mo; secondary if the child has been dry for at least 6 mo
EPIDEMIOLOGY
Incidence
• 15% of normal children have NE at age 5
• Of all children with incontinence:
– 70% with NE only
– 15% with daytime incontinence only
– 15% with daytime incontinence and NE
– 2–3% have NE into early adulthood without treatment
Prevalence
5–7 million with NE in the United States
RISK FACTORS
NE is multifactorial (see “Pathophysiology”“)
Genetics
• Primary NE tends to be familial:
– Both parents with history of NE—77% of children
– If one parent with history of NE—44% of children
• Several chromosomes have been linked to NE, including 12q, 13q, 22q
– 5HTR2A gene (13q14, serotonin receptor) mutation shown to be associated with NMNE
PATHOPHYSIOLOGY
• Complex, involving central nervous system, circadian rhythm (sleep and diuresis), and bladder function abnormalities
• 3 major pathogenic mechanisms:
– Increased arousal threshold
– Nocturnal polyuria
– Detrusor overactivity
• Some children lack normal nocturnal increase in vasopressin secretion leading to nocturnal polyuria, but not all children with polyuria are vasopressin deficient
• Overactive bladder leading to “small for age” bladder volume associated with NMNE
ASSOCIATED CONDITIONS
• Neuropsychiatric disorders (children with attention deficit hyperactivity disorder 2.7× more likely to have NE)
• Upper airway obstruction and nocturnal sleep apnea. Apneic episodes result in increased secretion of atrial natriuretic factor
• Constipation
• Urinary tract infection
GENERAL PREVENTION
MNE may not be preventable but parents should maintain regular voiding and bowel patterns—may help reduce risk of developing NMNE with LUTS.
DIAGNOSIS
HISTORY
• Detailed history helps determine treatment strategies
• Number of nights per week enuresis occurs?
• Symptoms suggestive of underlying bladder dysfunction:
– Drops of urine in underclothing before or after voiding
– Frequency of leakage (intermittent or continuous)
– Daytime incontinence in child over 31/2 yr of age
– Sudden urge to void
– Straining, posturing, holding maneuvers
– Interrupted micturition
– History of urinary tract infection
– Urinary tract malformation
Spinal cord or vertebral malformation
• Comorbidities that may predict treatment resistance:
– Constipation and encopresis
– Behavioral, psychological/psychiatric problems such as ADHD, ADD, autism
– Motor and/or learning disabilities or delayed development
– Pattern of fluid intake (incl. caffeine)
Does patient drink during the night?
PHYSICAL EXAM
• Abdominal exam for distended bowel/bladder
• Lower back inspection for stigmata of occult spinal dysraphism/tethered cord (sacral dimple, hair tuft, hemangioma, lipoma or other neurocutaneous signatures, absence of a palpable sacrum, or excess fat overlying the sacral region suggestive of a lumbosacral abnormality)
• Genital exam for congenital anomalies such as ectopic ureter or a urogenital sinus (with incontinence due to pooling of urine in the vagina)
– Labial adhesions in girls
– Urethral abnormalities or phimosis in boys
• Gait abnormalities, high arched foot
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Macroscopic urinalysis (dipstick) to determine glucosuria, proteinuria or UTI. If glucosuria present, obtain serum glucose at that time
• Microscopic urinalysis and culture if history of UTI or symptoms suggestive of infection
Imaging
• Children with MNE do not need imaging but a post-void residual (PVR) by bladder scan is useful
– US: May be considered in male patients, especially those who have failed initial therapy to ensure no anatomic problem
– Some suggest most males with enuresis should have bladder US to rule out posterior urethral valves
• Children with history of UTI or NMNE should undergo:
– Renal US
– PVR
– VCUG when diagnosis suggests posterior urethral valves or in older males; also used to evaluate for bulbar stricture (unusual)
– Abdominal x-ray to evaluate for vertebral abnormality; also assesses degree of stool retention although history is usually sufficient
– MRI of the spine for children suspected of having a neurogenic bladder as etiology, for those patients who are compliant and fail all therapeutic alternatives for NMNE, or who have a neurocutaneous signature or other physical findings on the lower spine or physical exam
Diagnostic Procedures/Surgery
• Uroflowmetry: Assesses bladder outlet obstruction or hypocontractility; evaluates voiding pattern (staccato)
• Urodynamics: Helpful in evaluating bladder compliance and function in children with severe dysfunctional voiding or enuresis due to neurogenic bladder or posterior urethral valves
• Cystoscopy: Routine use should be avoided
– May be helpful in the assessment of select patients with potential anatomic causes
Pathologic Findings
• Neurogenic bladder
• Ectopic ureter
• Posterior urethral valves
• Urethral stricture
DIFFERENTIAL DIAGNOSIS
• Ectopic ureter in girls, extremely rare in boys
• Giggle incontinence (enuresis risoria)
• Neurogenic bladder
• Nonneurogenic neurogenic bladder
• Posterior urethral valves (boys)
• Tethered cord
• Urethral stricture
• Vaginal voiding
TREATMENT
GENERAL MEASURES (2–6)
• Before embarking on any therapy, the interest and ability of the child and family to comply should be determined
• Patience and compliance should be emphasized because many months may be required to achieve improvement or resolution
• Motivational therapy should be encouraged in almost every case; it is useful in conjunction with other treatments
• Behavioral therapy is prerequisite to medications in most patients with monosymptomatic NE
• Enuresis alarm for MNE works with well-motivated families and children
– Treatment may take 2–3 mo
– Mechanism of action for behavioral therapy unclear
– Initial cure rate as high as 70%; suggest 4 mo of consecutive dryness
– Relapse can be high, but 50% achieve long-term cure
MEDICATION
First Line
• DDAVP (desmopressin) for NE:
– 0.2–0.6 mg PO 1 hr before bed. No fluid intake 2 hr before and 8 hr after bedtime
– Success rate ∼20–50%
– Caution in patients with cystic fibrosis (hyponatremic dehydration)
– Tapering schedule imperative
– Give parents copy of FDA warning (Dec 2007) regarding fluid intoxication and seizures (see “Additional Reading”)
Second Line
• Imipramine for NE: Tricyclic antidepressant with anticholinergic effects
– Success rates of 25–40%, but relapse rates can be high
– 25–50 mg
– Tapering schedule imperative
ALERT
Imipramine overdose can result in seizure, hypotension, coma, and fatal arrhythmias; may prolong QT interval.
• Oxybutynin (anticholinergic) for NMNE:
– 2.5–5 mg BID–QID (0.2 mg/kg/dose) when PVR negligible
– Available in long-acting form (5–10 mg/d)
– Success primarily when the medication is used with a well-organized treatment program including voiding 1st thing in the morning, timed voiding during the day, and regular bowel habits.
– Patients should be seen in 4–6 wk for evaluation including urinalysis and PVR. If elevated PVR, lower the dose and institute double voiding.
• Tolterodine (anticholinergic) for polysymptomatic or daytime incontinence:
– 1–2 mg BID. Also available in long-acting form (2–4 mg/d)
– More success when the medication is used with a well-organized treatment program
• Low-dose prophylactic antibiotics for NMNE:
– Helpful for children with recurrent UTI or bacteriuria with LUTS and voiding dysfunction
– Nitrofurantoin recommended 1–2 mg/kg QHS
SURGERY/OTHER PROCEDURES
• Only in cases of congenital anomalies (ectopic ureter, posterior urethral valves, etc.)
• Neurosurgical intervention for spinal anomalies, tethered cord
ADDITIONAL TREATMENT
Radiation Therapy
N/A
Additional Therapies
• Children with dysfunctional voiding/elimination syndromes may benefit from elimination retraining program and selective use of anticholinergic medications
– Use toilet at regular intervals during the day (every 21/2–3 hr)
– Waking children prior to the bedtime of the parents does not promote long-term dryness
• Fluid restriction useful and mandatory especially with dDAVP
• Treat constipation if present—patient should have at least daily bowel movements that are easy for the child to pass
Complementary & Alternative Therapies
• Pediatric biofeedback can be effective in cases of dysfunctional voiding. Most helpful in addition to improved voiding and bowel habits
– Child must have sufficient cognitive ability to understand teaching
ONGOING CARE
PROGNOSIS
• After age 5, spontaneous resolution rate of 15%/yr for bedwetters
• After age 15, <1% have NE
• Over 6.5 yr of follow-up:
– 91% no longer incontinent during the day
– 84% no longer wet at night
– With UTI history UTI, 82% no longer have infections
COMPLICATIONS
• Recurrent UTI
• Persistence of incontinence and LUTS—requires further investigation with VUDs and MRI
• Persistence of enuresis into adulthood (2–3%)
• Social consequences/withdrawal
FOLLOW-UP
Patient Monitoring
• Children with history of UTI or organic causes of enuresis should be followed for the specific condition
• Monitor closely while on medication to treat the enuresis (PVR and urinalysis)
Patient Resources
International Children’s Continence Society. http://i-c-c-s.org/parents/
REFERENCES
1. Neveus T, von Gontard A, Hoebeke P, et al. The standardization of terminology of lower urinary tract function in children and adolescents: Report from the Standardization Committee of the International Children’s Continence Society. J Urol. 2006;176(1):314–324.
2. Vande Walle J, Rittig S, Bauer S, et al. Practical consensus guidelines for the management of enuresis. Eur J Pediatr. 2012;171(6):971–983.
3. O’Flynn N. Nocturnal enuresis in children and young people: NICE clinical guideline British Journal of General Practice. 2011;61:360–362.
4. Jones EA. Urinary incontinence in children. In: Litwin MS, Saigal CS, eds. Urologic Diseases in America. Washington, DC: US Government Publishing Office; 2007.
5. Chase J, Austin P, Hoebeke P, et al. The management of dysfunctional voiding in children: A report from the Standardization Committee of the International Children’s Continence Society. J Urol. 2010;183(4):1296–1302.
6. Neveus T, Eggert P, Evans J, et al. Evaluation of and treatment for monosymptomatic enuresis: A standardization document from the International Children’s Continence Society. J Urol. 2010;183(2):441–447.
ADDITIONAL READING
2007 FDA advisory on DDAVP. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm125561.htm
See Also (Topic, Algorithm, Media)
• Dysfunctional elimination syndrome
• Enuresis, Adult
• Enuresis, Pediatric Algorithm 
• Urinary Tract Infection, Pediatric
• Vesicoureteral Reflux, Pediatric
CODES
ICD9
• 307.6 Enuresis
• 788.30 Urinary incontinence, unspecified
• 788.36 Nocturnal enuresis
ICD10
• F98.0 Enuresis not due to a substance or known physiol condition
• N39.44 Nocturnal enuresis
• R32 Unspecified urinary incontinence
CLINICAL/SURGICAL PEARLS
The primary therapy for all children with NE should be initial behavioral management before relying on medications.