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Enuresis: Diagnosis and Treatment of Bedwetting
Definition of Enuresis:
Enuresis is intermittent incontinence during periods of sleep after the fifth year of life lasting more than three months. Synonym: enuresis nocturna, although incontinence during the afternoon nap also belongs to the definition EAU Guidelines.
- Primary enuresis: when a child has not yet had a prolonged period of being dry.
- Secondary enuresis: enuresis after having stayed dry for at least six months.
- Monosymptomatic enuresis nocturna (MEN): nocturnal enuresis without any concurrent symptoms of bladder dysfunction (see below).
- Non-monosymptomatic enuresis nocturna (NMEN): Enuresis with concurrent symptoms of bladder dysfunction (overactive bladder, urge incontinence, holding maneuvers, detrusor-sphincter dyscoordination, bowel dysfunction or underactive bladder = lazy bladder).
Urinary incontinence in children:
Urinary incontinence in children includes all forms of urinary incontinence due to malformations, infections, neurological diseases, and bladder dysfunction. Obsolete synonyms: enuresis nocturna and diurna, complicated enuresis, enuresis diurna.
- Non-organic (functional) urinary incontinence: intermittent wetting during the day without sleep, after excluding organic causes.
- Continuous urinary incontinence: almost exclusively organically caused urinary incontinence without periods of dryness.
Epidemiology of Enuresis
- 7–13% of children over 7 have enuresis or childhood urinary incontinence. The spontaneous healing rate is 15% annually until puberty, the prevalence is then below 2%. The enuresis can rarely persist into adulthood.
- Boys : girls = 2:1
- 25% of the children show secondary enuresis and monosymptomatic enuresis occurs in about 2/3 of the cases.
Etiology: Causes of Enuresis
Enuresis is more of a symptom than a disease, and many aetiological factors are blamed. Not all components can be detected in individual cases. The child's ability to learn to control bladder function at night seems to be delayed in enuretic children. Some of the abnormalities described below are a normal part of development and can be detected (earlier) in continent children.
Immaturity of the CNS:
The immaturity of the CNS fail to recognize urinary bladder filling and to suppress the micturition reflex. Depending on the CNS maturity, there are different forms of enuresis, which are differentiated according to the respective waking reaction and the urinary bladder stability before the enuretic event (no waking reaction, unstable urinary bladder – slight waking reaction, stable urinary bladder – strong waking reaction, stable urinary bladder). Over time, enuretic children develop more robust waking reactions before wetting.
Reduced vasopressin secretion:
The circadian rhythm of vasopressin secretion leads to a halving of urine production during the night. Many children with enuresis have an abnormal rhythm of vasopressin secretion. The nightly urine production exceeds the urinary bladder capacity and leads to wetting. The disturbed vasopressin secretion may be a symptom of delayed CNS maturity. The urinary bladder filling also stimulates the vasopressin release. The nocturnal emptying of the bladder in enuretic children can explain (in part) the low nocturnal vasopressin concentration.
Infrequent and dysfunctional voiding:
Without anatomical disorders, infrequent voiding with holding maneuvers can lead to an increased sphincter tone, which no longer sufficiently relaxes while emptying the bladder. The resulting functional subvesical obstruction leads to detrusor hypertrophy, bladder instability, enuresis, and urge incontinence.
Genetics of enuresis:
The probability of enuresis is 77% if both parents were enuretic or 43% if one parent was enuretic. If there is no family history, the likelihood is 15%. The inheritance pattern suggests an autosomal dominant inheritance with a high penetrance of around 90%. In addition to the ENUR-1 gene on chromosome 13, other genes have been described on chromosomes 12 and 22 (Gontard et al., 2001).
Psychiatric comorbidities are more common in non-monosymptomatic enuresis than in monosymptomatic enuresis. Relapse or disease triggers are significant life events such as parents' separation or sibling birth. The most common comorbidities are attention deficit hyperactivity disorder (ADHD), conduct disorders, depression, and anxiety disorders.
Constipation and fecal incontinence are often associated with childhood urinary incontinence or non-monosymptomatic enuresis. The neural control of the urinary bladder and rectal evacuation are linked on various levels. In addition, retrovesical stool masses cause urinary bladder compression, favoring residual urine and detrusor overactivity.
Signs and Symptoms
The following four forms of enuresis should be distinguished, see section definitions above:
- Primary mononsymptomatic enuresis
- Primary non-monosymptomatic enuresis
- Secondary monosymptomatic enuresis
- Secondary non-monosymptomatisch enuresis
Diagnosis of Enuresis
The frequency and benign course of uncomplicated enuresis require that the initial diagnostics is reduced to a minimum. The basic workup should ensure that organically caused urinary incontinence is excluded.
Monosymptomatic enuresis is characterized by urinary incontinence during sleep (day or night) without symptoms such as frequency, urgency, or incontinence while awake. Specific questions address premature birth, urological diseases, symptoms of defecation, neurological complaints, or psychiatric abnormalities.
Carefully examine the anus and genitals for abnormalities: phimosis, vulvitis, labial synechia, or urine leakage from the vaginal introitus. A digital rectal examination is only necessary in exceptional cases and should be carried out by specialists if bowel disorders are present. Signs of spina bifida occulta are local hypertrichosis or atypical hairiness, hemangiomas or atypical pigmentation, coccyx fistula, or subcutaneous lipoma. Perform a simple neurological examination.
Offer a template to document drinking (time, volume), micturition (time, volume), and defecation (time) for two days. In addition, urgency symptoms or incontinence are recorded. Furthermore, over two weeks, the frequency of urinary incontinence (day/night) and stool abnormalities are recorded (simple tally sheet).
Perform urine analysis to exclude urinary tract infection.
Bladder sonography: Thickness of the urinary bladder wall over 5 mm? Residual urine? Stool retention: diameter of the rectum >3 cm with impression of the urinary bladder? Upper urinary tract sonography: kidney size? Hydronephrosis? Parenchymal scars?
Children with monosymptomatic enuresis do not need any further diagnostics. Further examinations are necessary if abnormalities are found or after unsuccessful therapy: uroflow with pelvic floor EMG, VCUG, urodynamics, renal scintigraphy, MR urography, or cystoscopy. Gastroenterology, psychiatry or nephrology experts should be consulted for corresponding symptoms.
Functional non-organic bladder dysfunction with incontinence, sleep apnea syndrome due to obstruction of the upper airways (tonsil hypertrophy, obesity), organic forms of urinary incontinence such as double kidney with ectopic ureter, vaginal influx, bladder dysfunction due to urethral valves in boys, epispadias, bladder exstrophy, cloacal malformations, sacral malformations, spina bifida, preterm birth, and trauma or tumors.
Treatment of Enuresis
From age 7, enuresis begins to cause social problems, as parents, friends, and the child want and expect continence.
Sequence of therapy of non-monosymptomatisch enuresis:
Priority to the treatment of urinary incontinence is the therapy of defecation disorders, which often also improves urinary incontinence. Manifest psychiatric diseases should also be treated first. The daytime urinary incontinence is then treated (if present), and finally, the symptoms of nocturnal enuresis.
Treatment options for enuresis:
Behavioral therapy is the basis of enuresis therapy. If this is unsuccessful, it is combined with drug or alarm therapy. Further treatment options are reserved for patients with non-monosymptomatic enuresis.
Behavioral therapy (Urotherapy):
The fundamentals of enuresis therapy are instructing the child to a regular drinking and micturition behavior. Micturitions and regular drinking every 2–2.5 hours should be planned with the help of a micturition diary and reminded with an alarm clock. The recommended drinking amount during the day is about 50 ml/kg body weight; most of the volume should be drunk by 5 p.m. Nothing should be drunk 1–2 hours before bedtime.
Further elements of behavioral therapy include training a relaxed sitting posture on the toilet, a reward system for dry nights, and the documentation of the treatment results by the child. With the help of an alarm clock, the child can wake up at night to empty the bladder before wetting.
Behavioral therapy is the treatment of the first choice because of its simplicity. If insufficient, good results are reported by the combination of medication and alarm therapy.
Drug Therapy of Enuresis
Desmopressin, anticholinergics, and tricyclic antidepressants are used to treat enuresis. Problems are the high recurrence rate after medication discontinuation, side effects, and the availability of non-drug treatment alternatives.
Desmopressin is an analog of vasopressin (1-deamino-8-D-arginine vasopressin, DDAVP) and reduces urine production at night and thus the frequency of enuresis. Unlike vasopressin, desmopressin does not affect smooth muscles or blood pressure. For pharmacology and side effects, see the section "Desmopressin". Many randomized studies and meta-analyses confirm the effectiveness of at least 50% and minimal side effects. The major drawback of desmopressin therapy is the 50–90% recurrence rate after stopping medication.
Dosage: Desmopressin is an oral, sublingual, or intranasal spray formulation. Start with 200 μg p.O. 0-0-1 over two weeks. If not effective, increase to 400 μg p.O. 0-0-1 for two weeks; the maximal dosage is 600 μg p.O. 0-0-1. Only if there is a significant treatment effect, continue desmopressin therapy for 3–6 months before gradually reducing desmopressin doses over 8 to 10 weeks. In the event of a relapse, another cycle of desmopressin can be given over three months after a short treatment-free break.
Anticholinergics increase functional bladder capacity and inhibit autonomic detrusor contractions. Anticholinergics are indicated if there is clinical or urodynamic evidence of reduced functional bladder capacity or an overactive bladder. Effectivity is higher after unsuccessful desmopressin therapy.
Dosage: e.g., Propiverine daily 0.8 mg/kg body weight in 2–3 doses. Treatment alternatives for children are trospium and oxybutinin. See also the section on pharmacology and side effects of anticholinergics.
Due to side effects, tricyclic antidepressants are a treatment option of third choice. The mechanism of action includes the anticholinergic effect of the antidepressants, an antidiuretic effect, and a putative effect on other transmitter systems. A complete treatment response can be expected in about 20–45% and an additional improvement in 15% of cases.
The side effects are problematic: sleep disturbance, nervousness, impaired appetite, nausea and vomiting, overdosing (limited therapeutic range), cardiotoxicity and a high probable recurrence after the termination of medication. The dosage of imipramine in children is 25–50 mg (1.5 mg/kg body weight) 0-0-1; there is no approval for the indication of enuresis (off-label medication).
Alarm training is an effective treatment option for motivated children, ideal for patients with MEN and only one wetting during the night. A diaper insert with a moisture sensor wakes the child during wetting. Classic conditioning during therapy leads to wakening before wetting and enables voiding on the toilet. The response to alarm training can be judged after 12–16 weeks.
The effectiveness and, compared to all other forms of therapy, the low recurrence rate after the end of treatment have been proven by many randomized trials and meta-analyses. Successful therapy can be expected in 50–80% of children after 8–10 weeks, with 2/3 of children getting dry and sleeping through the night and 1/3 of children needing to void in the night. Combining alarm therapy with other behavioral therapy methods (bladder training, pelvic floor exercises, and motivational training) improves the results. Critics accuse the alarm therapy of disturbing sleep behavior too drastically, leading to poor daytime concentration. The side effects of alarm training also affect all other family members, so alarm therapy is often discontinued.
Some authors advocate the so-called "Overlearning" after an excellent response to alarm training to consolidate the success of the therapy and avoid a relapse. The child is offered increased amounts of water to drink in the evening so that it has to wake up and void at night. Overlearning is controversial.
Treatment of LUTS and comorbidities:
Biofeedback therapy for dysfunctional voiding, alpha blockers for bladder neck obstruction, and specific treatment of psychiatric comorbidities.
Alternative forms of therapy, such as acupuncture and hypnosis, are available, but the evidence level is poor.
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S2 Leitlinie auf AWMF.org: Enuresis und nicht-organische (funktionelle) Harninkontinenz bei Kindern und Jugendlichen
EAU guidelines: Paediatric Urology
von Gontard, A.; Schaumburg, H.; Hollmann, E.; Eiberg,
H. & Rittig, S.
The genetics of enuresis: a review.
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Hjalmas, K.; Arnold, T.; Bower, W.; Caione, P.;
Chiozza, L. M.; von Gontard, A.; Han, S. W.; Husman, D. A.; Kawauchi, A.;
LAckgren, G.; Lottmann, H.; Mark, S.; Rittig, S.; Robson, L.; Walle, J. V.
& Yeung, C. K.
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Schultz-Lampel und Thüroff 2000 SCHULTZ-LAMPEL, D. ;
THÜROFF, J. W.:
Enuresis und kindliche Harninkontinenz.
In: THÜROFF, JW (Hrsg.) ; SCHULTE-WISSERMANN, H (Hrsg.): Kinderurologie in Klinik und Praxis.
Stuttgart New York : Thieme, 2000, S. 265–275
Deutsche Version: Ursachen und Diagnose der Enuresis und Therapie der kindlichen Harninkontinenz