Sleep enuresis …

Rosalia C Silvestri MD

Sleep Disorders

Updated 08.07.2020
Released 11.11.1994
Expires For CME 08.07.2023

Sleep enuresis

Author: Rosalia C Silvestri MD

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Editor: Antonio Culebras MD FAAN FAHA FAASM

Sleep enuresis

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Introduction

This article includes discussion of sleep enuresis, nocturnal enuresis, enuresis nocturna, nocturnal bedwetting, familial enuresis, functional idiopathic enuresis, symptomatic enuresis, and essential enuresis. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

The author points out how therapeutic strategies stress a combined pharmacologic/behavioral approach for therapy-resistant enuresis, especially when psychiatric comorbidity is diagnosed.

Key points

	• Primary nocturnal enuresis is a common parasomnia often comorbid with neurodevelopmental disorders.
	• A combination of pharmacological treatment and behavioral therapy with the aid of mechanical alarm devices is highly successful at almost any age.
	• Social embarrassment and stigmata may be easily overcome by appropriate management.

Historical note and terminology

One of the most prevalent and distressing of the childhood parasomnias, sleep enuresis has been discussed in medical papers since 1550 BC (33). Understanding of the problem has developed slowly, and many enuretic children remain untreated or are treated ineffectively.

Early sleep research suggested that enuresis occurred as a "dream equivalent" (62). Later, Broughton proposed that enuresis is a disorder of arousal, originating in the deepest NREM sleep stage (14), but Mikkelsen and Rapoport demonstrated that enuretic episodes occur more or less randomly throughout the night, independent of sleep stage (50).

Clinical manifestations

Presentation and course

Sleep enuresis is characterized by recurrent involuntary urination during sleep. Primary sleep enuresis refers to failure to attain urinary control from infancy; secondary enuresis denotes a relapse after control has been achieved. Sleep enuresis typically is diagnosed when involuntary bedwetting occurs after 5 years of age in girls and 6 years of age in boys. A minority of children with sleep enuresis also have daytime (waking) enuresis.

Primary sleep enuresis is continuous from infancy, with wetting from once or twice a week to nightly, and often several times a night. In secondary sleep enuresis, the child has been dry for at least 3 months.

Approximately 25% of all children have some relapse of bedwetting after a period of initial dryness. This bedwetting generally is self-limiting and associated with illness or stress. Sleep enuresis usually disappears spontaneously at a rate of 15% per year after 5 years of age.

Sleep enuresis also occurs in the elderly: about 3% of women and 1% of men over the age of 65 years have the disorder (15).

Prognosis and complications

Sleep enuresis is often kept secret when it persists beyond childhood, as it causes embarrassment and inconvenience. Daily changing of sheets and concerns about odor are typical. Primary sleep enuresis restricts the child's range of activities, such as spending the night with a friend, going on trips, or camping. The psychological trauma is often the most serious complication. When children and families wait for resolution without therapy or counseling, the social and emotional hardships associated with incontinence can result in developmental problems, conduct problems, and child abuse.

With increased age and duration of symptoms, the self-esteem domain of quality of life worsens. Also, there seems to be a significant correlation between sleep quality parameters from the Pittsburgh Sleep Quality Index and the physical well-being domain of the Quality of Life questionnaire (27).

There seems to be a strong association of enuresis with attention-deficit hyperactivity disorder (ADHD); a 16.9% prevalence of enuresis was described in an ADHD cohort where the likelihood of inattentive symptoms was higher than in the nonenuretic group (25). Deficits in arousal could probably contribute to both enuresis and ADHD. Another study found an odds ratio of 2.88 for ADHD and enuresis comorbidity and advocated a routine ADHD evaluation for enuresis and vice versa (70).

Clinical vignette

A 10-year-old boy was referred for evaluation of bedwetting. He had never been dry at night for a substantial period and was enuretic between 3 and 7 times weekly, but he did not have daytime enuresis or urgency. His parents described him as a deep sleeper who was difficult to awaken.

Intravenous pyelogram, urinalysis, and urine cultures performed previously were normal. Treatments with fluid restriction and oxybutynin had been unsuccessful. Imipramine had produced modest benefits but was discontinued because of sleep disruption and daytime behavioral problems.

He had a history of allergic asthma. Family history was positive for sleeptalking in both parents but was negative for enuresis. His father was a physician, and his mother was active in community affairs. The patient, the second of 2 children, was an excellent student. There were no major family conflicts, but the parents had differing parenting styles; the father was considered distant and occasionally hostile by the mother, whereas the mother was considered overly protective by the father. Physical and mental status examinations were normal.

The impression was primary sleep enuresis. Treatments with bladder retention exercises and sphincter exercises were prescribed along with the bell-and-pad method. Family counseling was also recommended, but the father was unwilling to consider this approach.

At follow-up 3 months later, the patient had used the bell-and-pad regularly but had performed the bladder and sphincter exercises only occasionally. The frequency of enuresis dropped initially to 1 to 3 times weekly but then increased again to 5 to 7 times weekly. The patient was encouraged to continue with the bell-and-pad and was prescribed desmopressin 20 µg intranasally at bedtime. Over the next 3 months, he was enuretic only 3 times. He continued to do well with the combined treatment for 5 more months. During this time, marital difficulties worsened, and the parents separated. Desmopressin was then discontinued, but enuresis returned and the medication was restarted and continued for another 6 months. Following discontinuation of the medication, he continued to do well, despite the divorce of his parents, with only occasional enuretic episodes over the next 6 months.

Biological basis

Etiology and pathogenesis

The pathologic basis of uncomplicated primary enuresis is unknown. Proposed causes or contributors include central nervous system immaturity, primary disorder of arousal, excess fluid intake, impaired ability to concentrate urine, psychosocial factors, and such bladder abnormalities as small size or increased contractility. Other risk factors include male gender, stress and psychosocial problems within the family, attention-deficit hyperactivity disorder, maternal smoking, and maternal age less than 20 years at the time of the child’s birth (64; 67). Causes of secondary enuresis can be structural, pathological, or psychological.

The biological basis for primary sleep enuresis is unclear. An interaction of genetic psychological, neurologic, urologic, endocrinologic, autonomic, sleep-related, and developmental factors is suspected, but the relative importance of these factors varies across individuals and is often multifactorial. Some children have enuretic episodes following normal cystometrogram activity whereas others have uninhibited contractions of the bladder during deep NREM sleep (41). Similarly, some children have brief arousals prior to bedwetting whereas others do not (41). Autonomic nervous system studies suggest parasympathetic hyperactivity in some children (88).

Psychological factors such as posttraumatic stress contribute to enuresis in some children, and parental anxiety and expectation play a role in others. Children who are bullied are more likely to have enuresis, and in a study of 134 children before and after a flood in Bangladesh, one third developed a new problem with enuresis after the disaster (22; 85). However, psychosomatic complaints are not increased in enuretic children, and there are no major emotional or behavioral differences between children with enuresis, children who have outgrown enuresis, and children who have never had enuresis (83; 84; 38; 30).

Although there are no major group differences in sleep patterns between enuretic and nonenuretic children, obstructive sleep apnea appears to contribute to enuresis in some children and adults (77; 43; 81). In addition, boys with sleep enuresis are more difficult to arouse from sleep than boys without enuresis (83; 86). Nevus and colleagues studied children with primary sleep-related enuresis polysomnographically prior to and following treatment with desmopressin. Approximately half responded to treatment and half did not. Interestingly, children who responded to desmopressin therapy spent more time in REM sleep than those children who were nonresponders (57). Although sleep of enuretic children does not seem to differ significantly from that of nonenuretic children, those who suffer from primary sleep-related enuresis spend a slightly longer time in bed and have an increased number of sleep cycles. Children who void during REM sleep are found to have more REM sleep than others. Tachycardia is often seen to precede the enuretic event. Although sleep of enuretic children seems to be polysomnographically normal, the children can exhibit signs of autonomic arousal prior to voiding (05).

Nocturnal mean arterial pressure was found to be significantly higher in children with enuresis and polyuria than in children without polyuria, with no significant difference between wet and dry nights within this sample (44).

Studies have analyzed sleep quality of enuretic children by means of Pittsburg Sleep Quality Index (PSQI) questionnaire and found a poor quality of sleep, successively improved by a month with desmopressin (desmopressin acetate) therapy (36; 27). In particular, anxiety and fear seem to play a negative role in sleep perception. PSQI subscales relating to excessive daytime sleepiness (p< 0.003) and daytime behavior (p< 0.000) were significantly worse in enuretic children, whereas snoring subscale scores were significantly higher only in female enuretic subjects, suggesting a link between enuresis and sleep-disordered breathing in girls (72). Sleep-disordered breathing should be ruled out in all enuretic children with excessive daytime sleepiness who do not respond to standard treatment.

Genetic factors may play a role in some cases. Enuresis is more common in children of enuretics than in the general population, and in some families, the pattern of involvement is consistent with an autosomal dominant inheritance with high penetrance. Genetic studies suggest linkage of primary sleep enuresis to markers on chromosome 12, 13, and 22 (Eiberg et al 1995; 04; 79; 24). Associations between genotype and phenotype are complex and susceptible to environmental influences. Exact assessment of the clinical phenotype and identification of intermediary phenotypes or traits of enuretic children are necessary (80). Nonetheless, expectations by enuretic parents that their children will be enuretic probably contribute to some degree to the familial clustering of sleep enuresis.

Rs6313 polymorphism in 5-hydroxytriptamine receptor 2A (5HTR2A) gene has been associated with polysymptomatic primary nocturnal enuresis (PPNE) (82). Previous evidence of SSRIs efficacy in PPNE prompted the search for a possible genetic receptor link. The study revealed that TT and TC genotypes were both associated with higher risk for PPNE compared with CC (OR 10.71 and 2.68 respectively, p= 0.0002). Also allele T alone compared with allele C (OR= 3.7, p=0.000015) had a higher frequency in PPNE, this evidence suggesting that genetic variance of 5HTR2A transmission may influence therapeutic response of PPNE.

Some enuretic children lack a normal nighttime peak in antidiuretic hormone levels, with resultant high overnight urine output (59; 01). In these children, the amount of urine produced during the night may exceed the maximum daytime functional capacity, thereby leading to enuresis. However, studies have confirmed the established fact that arginine vasopressin secretion is a function of plasma osmolality, contracting the hypothesis that enuretic children are deficient in arginine vasopressin. Results of investigations in children with nocturnal enuresis compared to normal controls pointed to central action of desmopressin, a defect at the central arginine vasopressin receptor level or the signal transduction pathway (23).

In children with primary enuresis, structural abnormalities of the urinary tract are uncommon, and little evidence supports a proposed association between a small functional bladder capacity and sleep enuresis (42).

Among elderly adults with sleep enuresis, congestive heart failure and regular use of sleep medications appear to be contributing factors (15).

Epidemiology

The reported prevalence of sleep enuresis varies according to its definition; sleep enuresis may be defined by a range of frequencies, from bedwetting at least once per week to bedwetting at least once in 3 months. Using a definition based on bedwetting at least once per month, sleep enuresis has a prevalence of approximately 80% in 2 year olds, 30% in 4 year olds, 18% in 5 year olds, 10% in 6 year olds, 8% in 8 year olds, 3% to 4% in 12 year olds, and 1% in 15 year olds (10; 17; 73). With enuresis defined as at least 1 wet night in 3 months, it has a prevalence of 8% in healthy children aged 7 to 15 years (49). Boys at all ages are affected more often than girls. Approximately 15% of bed-wetters achieve nocturnal control each year.

A study of 656 Yemen school children (via questionnaires completed by parents) found a total of 17.2% experienced nocturnal enuresis, which decreased by age from 31.5% at 6 to 8 years to 8.7% at 15 years and older (p< 0.05); 76.% of those experienced primary nocturnal enuresis with nightly bedwetting (89).

Primary enuresis accounts for 75% to 80% of enuretic cases, with secondary enuresis representing the remaining 20% to 25%. By 12 years of age, 50% of all cases of enuresis are of the secondary type. Fifteen percent to 20% of sleep enuretics have diurnal enuresis, a prevalence that rapidly decreases after 5 years of age.

A high correlation exists between a family history of enuresis and enuresis in children. Studies suggest an incidence of 77% when both parents were enuretic as children and a rate of 44% in children when 1 parent has a history of enuresis. In approximately 70% of families with an enuretic child, at least 1 other sibling also has had the problem.

Prevalence figures are similar in all societies, whether industrialized or primitive. However, the prevalence of sleep enuresis is higher in lower socioeconomic groups, where parenting skills or expectations may be less developed and toilet training may not be encouraged or achieved. Enuresis also is more prevalent among developmentally delayed youngsters, institutionalized children, and those with sickle cell anemia, attention-deficit hyperactivity disorder, or obstructive sleep apnea syndrome (63; 64; 81). The prevalence rate of ADHD is increased in an enuretic population compared to community samples (3% to 5%) (06). Several studies have indicated a greater frequency of enuresis in black than in white children (67). Among older adults, the risk of sleep enuresis is increased with Graves disease, congestive heart failure, and the use of sleeping medications (15; 35).

Differential diagnosis

Patients with sleep enuresis, a normal physical examination, and negative urinalysis and urine culture findings have uncomplicated enuresis. Such children may have associated mild daytime urinary frequency or enuresis, a positive family history of enuresis, and slightly delayed developmental achievements.

Patients with a positive urine culture or history of urinary tract infection, abnormal neurologic examination, or history of significant voiding dysfunction have complicated enuresis, which may be caused by urinary infection, diabetes mellitus, diabetes insipidus, epilepsy, sickle cell anemia, or neurologic disorders. Sleep-related enuresis is often associated with obstructive sleep apnea syndrome. Brooks and colleagues have shown a high prevalence of enuresis in children with suspected sleep-disordered breathing. Children with a respiratory disturbance index greater than 1 event per hour of sleep were at higher risk for enuresis than children with a respiratory disturbance index of less than or equal to 1 event per hour. This may be due to the effects of obstructive sleep apnea on arousal response, bladder pressure, or urinary hormone secretion (13). Asthmatic children with wheezing in the last 12 months were found to be 2.33 times more likely to have had enuretic episodes at any time in their life according to questionnaires sent out to their guardians/parents (21). Whether this correlation, as it might be supposed, depends on obstruction of the airways remains to be seen. Sleep enuresis also commonly occurs in children who suffer from NREM sleep parasomnias, such as sleep terrors or sleep walking.

A pathologic process involving the urinary tract is likely if the child has daytime enuresis, abnormalities in the initiation of urination, or abnormal urinary flow. Secondary enuresis may be associated with obstructive sleep apnea or sexual abuse (26).

Management

Treatment must begin with a determination as to whether the child has uncomplicated or complicated enuresis. In most children, the disorder is uncomplicated and requires parental support, empathy, and patience. A common approach for otherwise normal children is to wait and see if the bedwetting problem is "outgrown." For most, it resolves spontaneously. The annual spontaneous cure rate between 5 and 19 years of age is about 15% per year.

When the child or parents desire more rapid resolution, treatment also may involve behavioral techniques (behavior modification, wetness alarms, and retention control exercises), fluid restriction, medication, psychotherapy, hypnosis, surgery, biofeedback, or a combination of these (48). Behavioral techniques are more likely to be successful in children over the age of 6 than in younger children.

Systems that incorporate an alarm are commonly used behavioral techniques. Although medications were at one time the favored approach, physicians now appear to be more likely to recommend behavioral techniques, at least in some communities (78). The bell-and-pad method involves having the child sleep on a pad, which incorporates an alarm that sounds when the pad is wet. The alarm wakes the child, who stops voiding, turns off the alarm, and goes to the bathroom to finish voiding. Newer urine alarms, which attach to the child's pajamas, also condition the child to awaken when urinating at night and eventually to awaken at the sensation of bladder distention. The success rate for these devices is 65% to 80%, with relapses in 10% to 15% of cases (52). Comparative trials show that the urine alarm is superior to drug therapy and is the most effective treatment for enuresis, with increased nocturnal bladder capacity and higher rates of sustained continence (54; 61).

A study to determine the efficacy of bell and pad alarm therapy as initial and relapse treatment for nocturnal enuresis, and to explore risk factors for treatment failure and for relapse within 12 months of successful therapy, found an initial response rate of 84% and relapse rate of 30%, whereas effective therapy after relapse was 78%, with an average length of treatment of 10 weeks (32). Female gender, motivation, absence of diurnal symptoms, and shorter length of treatment were associated with successful therapy.

The enuresis alarm can be combined with positive reinforcement, nighttime awakenings, retention control (increasing urine retention before voiding), cleanliness training (cleaning up after an episode), and positive practice (imaging followed by voiding in a bathroom). Such combined approaches are sometimes superior to the use of an alarm alone.

Medications include antidepressants, antidiuretics, antispasmodics, and prostaglandin synthesis inhibitors.

Desmopressin (10 to 40 µg intranasally or 200 to 600 µg orally) is the primary antidiuretic prescribed for enuresis. This therapy is indicated in case of nocturnal polyuria due to free water diuresis linked to vasopressin deficiency (56). Although the medication usually reduces the frequency of wetting, only a small minority of patients obtain complete dryness (53; 29; 71). Treatment effects usually last only as long as the drug is taken. Side effects are uncommon. Hyponatremia and water intoxication with seizures are rare complications (74; 65). There does not appear to be a relationship between a positive family history of enuresis and response to desmopressin (69). Desmopressin with an alarm or other behavioral treatments may be the best overall therapy as the combined approach appears to be superior to either given alone (12; 11). Indication for the treatment of primary nocturnal enuresis was removed from all intranasal preparations of desmopressin in 2007. Within a few months, the proportion of oral tablet prescriptions increased to 80% (39). Anticholinergic agents can be combined with desmopressin for better efficiency in therapy-resistant enuresis (55).

A retrospective observational study explored the efficacy of desmopressin or anticholinergic treatment in nocturnal enuresis or daytime voiding symptoms in children with ADHD and autism spectrum disorder. The study showed a favorable trend toward efficacy of desmopressin and anticholinergic therapy in autistic children with an 8-month mean time to cure in 50% of children with an autism spectrum disorder and nocturnal enuresis (34).

The tricyclic antidepressant imipramine is frequently prescribed; its effectiveness appears to derive from increased alpha-adrenergic stimulation of proximal tubules of the kidney (31; 40). Typical doses are 25 mg 1 to 2 hours before bedtime for patients 6 to 8 years of age and 50 to 75 mg for older children and adolescents. Unfortunately, the long-term cure rate is only 25% and the relapse rate is high. Imipramine has become increasingly unfavorable as a primary treatment of sleep-related enuresis due to the high relapse rate, and fatal overdose is a significant possibility (37). Among modern antidepressants, reboxetine has been successfully used as an alternative to imipramine (Lundmark and 56). A review on the use of tricyclic and related drugs for nocturnal enuresis in children included over 64 trials involving 4071 children (18). The authors concluded that as a short-term outcome, tricyclics are better than placebo, but potentially harming serious adverse effects cannot be ruled out and do not justify a relatively small and transient effect size. Oxybutynin chloride (5 mg at bedtime for 8 year olds to 5 mg 3 times per day for teenagers), has a direct spasmolytic effect on the bladder and is helpful in controlling diurnal enuresis and uninhibited bladder contractions, but it has little or no effect on sleep enuresis.

Tolterodine can also be used alternatively in children with detrusor instability alone or in association with desmopressin (66). Even diuretic treatment has been considered (furosemide 1 mg/Kg in the afternoon) as an alternative of desmopressin for treatment of nocturnal polyuria (58). Results showed, however, only a mild therapeutic response in nocturnal enuresis especially for children unresponsive to desmopressin.

In a randomized, double-blind, placebo-controlled cross-over design investigation, Al-Waili has shown carbamazepine to be useful in treatment of primary enuresis (02). However, prior to randomization, comprehensive evaluation of sleep using polysomnography or EEG was not done.

Psychotherapy is of value when sleep enuresis is related to posttraumatic stress, emotional disturbances, or family conflicts. Improvements have also been reported with hypnotherapy, and in some studies, the benefits were more enduring than with imipramine (07). Bjorkstrom and colleagues have investigated electro-acupuncture in the treatment of children with monosymptomatic nocturnal enuresis and found that there were more dry nights in 65% of the children (08). However, only 5 of 23 children were considered responders (greater than 90% reduction in the number of wet nights at the 6-month follow-up evaluation). Interestingly, according to the parents, the sleep arousal threshold had decreased in about 50% of the children.

The success of any of these approaches may be attributed in part to the spontaneous cure rate or to the patient's response to increased attention to the problem. Emotional support of the child is probably the most critical element of any treatment program.

Acupuncture as part of a traditional Chinese medicine approach is rated superior to the efficacy rate of alarm therapy, whereas it would be less effective when used as a monotherapy. Electro-acupuncture enhances treatment outcome and allows standardization of the intervention (09).

A report on the efficacy of acupuncture noticed the need of 78 treatment sessions to achieve results and more in older children as they were all deep sleepers (90). A systematic review and metaanalysis of randomized and nonrandomized studies found an overall favorable, but not significant, effect of acupuncture compared with conventional care and placebo, with minor and rare side effects (68).

Sleep architecture parameters predict postoperative nocturnal enuresis resolution in children with obstructive sleep apnea undergoing adenotonsillectomy (75). In children with severe obstructive sleep apnea and prolonged stage 2 sleep on polysomnography, 51.4% of 37 pediatric patients undergoing adenotonsillectomy were 3.4 times more likely to resolve their primary nocturnal enuresis postoperatively, even if they had an elevated BMI. Resolution of sleep fragmentation and increased arousal were thought to be key to explain such improvement.

An additional article from Japan reported improvement of nocturnal sleep in enuretic children following yokukansan, a partial D2 agonist, 5-HT1A agonist, and 5-HT2A antagonist (60). Following bedtime administration, 10 of 18 patients achieved a full response.

Among the ultimate treatment proposals, transcutaneous parasacral electric stimulation has been used in patients with an overactive bladder, with a complete response rate as monotherapy of 43% in one study and 70.4% in the most recent report on this option (Lordelo el al 2010; 76). Functional magnetic stimulation is also regarded as a promising treatment modality in girls and in children with cortical arousal dysfunction, where the periaqueductal area might be deactivated in response to bladder dysfunction (16; 87).

A synopsis of systematic reviews indicates that alarms, desmopressin, and some tricyclics (imipramine, desipramine, viloxazine, and amitriptyline) may be efficacious in the management of nocturnal enuresis (47). Some simple behavioral interventions, such as managing fluid intake, retention control training, and motivation by rewards, also seem beneficial, whereas complex behavioral interventions or combinations of treatment modalities are not supported by definitive data.

References

01: Aikawa T, Kasahara T, Uchiyama M. The arginine-vasopressin secretion profile of children with primary nocturnal enuresis. Eur Urol 1998;33(Suppl 3):41-4. PMID 9599737
02: Al-Waili NS. Carbamazepine to treat primary nocturnal enuresis: a double-blind study. Eur J Med Res 2000;5:40-4. PMID 10657288
03: Arda E, Cakiroglu B, Thomas DT. Primary nocturnal enuresis: a review. Nephrourol Mon 2016;8(4):e35809. PMID 27703953
04: Arnell H, Hjalmas K, Jagervall M, et al. The genetics of primary nocturnal enuresis: inheritance and suggestion of a second major gene on chromosome 12q. J Med Genet 1997;34:360-5. PMID 9152831
05: Bader G, Neveus T, Kruse S, Sillen U. Sleep of primary enuretic children and controls. Sleep 2002;25:579-83. PMID 12150325
06: Baeyens D, Roeyers H, D’Haese L, Pieters F, Hoebeke P, Vande Walle J. The prevalence of ADHD in children with enuresis: comparison between a tertiary and non tertiary care sample. Acta Paediatr 2006;95(3):347-52. PMID 16497647
07: Banerjee S, Srivastav A, Palan BM. Hypnosis and self-hypnosis in the management of nocturnal enuresis: a comparative study with imipramine therapy. Am J Clin Hypn 1993;36:113-9. PMID 8259762
08: Bjorkstrom G, Hellstrom AL, Andersson S. Electro-acupuncture in the treatment of children with monosymptomatic nocturnal enuresis. Scand J Urol Nephrol 2000;34:21-6. PMID 10757265
09: Bower WF, Diao M. Acupuncture as a treatment for nocturnal enuresis. Auton Neurosci 2010;157:63-7. PMID 20728414
10: Bower WF, Moore KH, Shepherd RB, Adams RD. The epidemiology of childhood enuresis in Australia. Br J Urol 1996;78:602-6. PMID 8944518
11: Bradbury M. Combination therapy for nocturnal enuresis with desmopressin and an alarm device. Scand J Urol Nephrol 1997;183(Suppl):61-3. PMID 9165611
12: Bradbury MG, Meadow SR. Combined treatment with enuresis alarm and desmopressin for nocturnal enuresis. Acta Paediatr 1995;84:1014-8. PMID 8652952
13: Brooks LJ, Topol HI. Enuresis in children with sleep apnea. J Pediatr 2003;142:515-8. PMID 12756383
14: Broughton RJ. Sleep disorders: disorders of arousal. Enuresis, somnambulism, and nightmares occur in confusional states of arousal, not in "dreaming sleep". Science 1968;159:1070-8. PMID 4865791
15: Burgio KL, Locher JL, Ives DG, Hardin JM, Newman AB, Kuller LH. Nocturnal enuresis in community-dwelling older adults. J Am Geriatr Soc 1996;44:139-43. PMID 8576502
16: But I, Varda NM. Functional magnetic stimulation: a new method for the treatment of girls with primary nocturnal enuresis? J Pediatr Urol 2006;2(5):415-8. PMID 18947648
17: Byrd RS, Weitzman M, Lanphear NE, Auinger P. Bedwetting in US children: epidemiology and related behavior problems. Pediatrics 1996;98:414-9. PMID 8784366
18: Caldwell PH, Sureshkumar P, Wong WC. Tricyclic and related drugs for nocturnal enuresis in children. Cochrane Database Syst Rev 2016;(1):CD002117. PMID 26789925
19: Charalampous S, Printza N, Hashim H, et al. Bladder wall thickness and urodynamic correlation in children with primary nocturnal enuresis. J Pediatr Urol 2013;9(3):334-8. PMID 22652388
20: Cvitkovic-Kuzmic A, Brkljacić B, Ivanković D, Grga A. Ultrasound assessment of detrusor muscle thickness in children with non-neuropathic bladder/sphincter dysfunction. Eur Urol 2002;41(2):214-8. PMID 12074411
21: Dahan P, de Bessa J Jr, de Oliveira DM, et al. Association between asthma and primary nocturnal enuresis in children. J Urol 2016;195(4 Pt 2):1221-6. PMID 26926555
22: Durkin MS, Khan N, Davidson LL, Zaman SS, Stein ZA. The effects of a natural disaster on child behavior: evidence for posttraumatic stress. Am J Public Health 1993;83(11):1549-53. PMID 8238676
23: Eggert P. What’s new in enuresis. Acta Paediatrica Taiwanica 2002;43:6-9. PMID 11890230
24: Eiberg H. Total genome scan analysis in a single extended family for primary nocturnal enuresis: evidence for a new locus (ENUR3) for primary nocturnal enuresis on chromosome 22q11. Eur Urol 1998;33(Suppl 3):34-6. PMID 9599735
25: Elia J, Takeda T, Deberardinis R, et al. Nocturnal enuresis: a suggestive endophenotype marker for a subgroup of inattentive attention-deficit/hyperactivity disorder. J Pediatr 2009;155(2):239-44.e5. PMID 19446845
26: Elliott AJ, Peterson LW. Maternal sexual abuse of male children. When to suspect and how to uncover it. Postgrad Med 1993;94:169-80. PMID 8321770
27: Ertan P, Yilmaz O, Caglayan M, Sogut A, Aslan S, Yuksel H. Relationship of sleep quality and quality of life in children with monosymptomatic enuresis. Child Care Health Dev 2009;35(4):469-74. PMID 19438876
28: Fergusson DM, Hons BA, Horwood LJ, Shannon FT. Factors related to the age of attainment of nocturnal bladder control: an 8-year longitudinal study. Pediatrics 1986;78:884-90. PMID 3763302
29: Folwell AJ, Macdiarmid SA, Crowder HJ, Lord AD, Arnold EP. Desmopressin for nocturnal enuresis: urinary osmolality and response. Br J Urol 1997;80:480-4. PMID 9313673
30: Friman PC, Handwerk ML, Swearer SM, McGinnis JC, Warzak WJ. Do children with primary nocturnal enuresis have clinically significant behavior problems. Arch Pediatr Adolesc Med 1998;152:537-9. PMID 9641705
31: Fritz GK, Rockney RM, Yeung AS. Plasma levels and efficacy of imipramine treatment for enuresis. J Am Acad Child Adolesc Psychiatry 1994;33:60-4. PMID 8138522
32: Gim CS, Lillystone D, Caldwell PH. Efficacy of the bell and pad alarm therapy for nocturnal enuresis. J Paediatr Child Health 2009;45(7-8):405-8. PMID 19712175
33: Glicklich LB. An historical account of enuresis. Pediatrics 1951;8:859-76. PMID 14911258
34: Gor RA, Fuhrer J, Schober JM. A retrospective observational study of enuresis, daytime voiding symptoms, and response to medical therapy in children with attention deficit hyperactivity disorder and autism spectrum disorder. J Pediatr Urol 2012;8(3):314-7. PMID 21131234
35: Goswami R, Seth A, Goswami AK, Kochupillai N. Prevalence of enuresis and other bladder symptoms in patients with active Graves' disease. Br J Urol 1997;80:563-6. PMID 9352693
36: Gozmen S, Keskin S, Akil I. Enuresis nocturna and sleep quality. Pediatr Nephrol 2008;23(8):1293-6. PMID 18506489
37: Harari MD, Moulden A. Nocturnal enuresis: what is happening. J Paediatr Child Health 2000;36:78-81. PMID 10723698
38: Hirasing RA, van Leerdam FJ, Bolk-Bennink LB, Bosch JD. Bedwetting and behavioural and/or emotional problems. Acta Paediatrica 1997;86:1131-4. PMID 9350899
39: Hoffmann F, Glaeske G, Steuber C. Did the removal of the indication of nocturnal enuresis for intranasal desmopressin change prescribing practice. Pharmacoepidemiol Drug Saf 2011;20(1):105-9. PMID 21182158
40: Hunsballe JM, Rittig S, Pedersen EB, Olesen OV, Djurhuus JC. Single dose imipramine reduces nocturnal urine output in patients with nocturnal enuresis and nocturnal polyuria. J Urol 1997;158:830-6. PMID 9258093
41: Imada N, Kawauchi A, Kitamori T, Ohne T, Tanaka Y, Watanabe H. Long-term results of systematic treatment for nocturnal enuresis based on overnight simultaneous monitoring of electroencephalography and cystometry. Nippon Hinyokika Gakkai Zasshi 1996;87:1114-9. PMID 8914394
42: Kawauchi A, Watanabe H, Miyoshi K. Early morning urine osmolality in nonenuretic and enuretic children. Pediatr Nephrol 1996;10(6):696-8. PMID 8971881
43: Kramer NR, Bonitati AE, Millman RP. Enuresis and obstructive sleep apnea in adults. Chest 1998;114:634-7. PMID 9726759
44: Kruse A, Mahler B, Rittig S, Djurhuus JC. Increased nocturnal blood pressure in enuretic children with polyuria. J Urol 2009;182(4 Suppl):1954-60. PMID 19695582
45: Lordelo P, Benevides I, Kerner EG, Teles A, Lordêlo M, Barroso U Jr. Treatment of non-monosymptomatic nocturnal enuresis by transcutaneous parasacral electrical nerve stimulation. J Pediatr Urol 2010;6(5):486-9. PMID 20837326
46: Lundmark E, Neveus T. Reboxetine in therapy-resistant enuresis: a retrospective evaluation. Scand J Urol Nephrol 2009;43(5):365-8. PMID 19921980
47: Mathew JL. Evidence-based management of nocturnal enuresis: an overview of systematic reviews. Indian Pediatr 2010;47(9):777-80. PMID 21048259
48: Mattelaer P, Mersdorf A, Rohrmann D, Jung P, Jakse G. Biofeedback in the treatment of voiding disorders in childhood. Acta Urol Belg 1995;63:5-7. PMID 8644555
49: Mattsson S. Urinary incontinence and nocturia in healthy schoolchildren. Acta Paediatr 1994;83:950-4. PMID 7819693
50: Mikkelsen EJ, Rapoport JL. Enuresis: psychopathology, sleep stage, and drug response. Urol Clin North Am 1980;7:361-77. PMID 6996271
51: Mimouni M, Shuper A, Mimouni F, Greunebaum M, Varsano I. Retarded skeletal maturation in children with primary enuresis. Eur J Pediatr 1985;144:234-5. PMID 4054161
52: Moffatt ME. Nocturnal enuresis: a review of the efficacy of treatments and practical advice for clinicians. J Dev Behav Pediatr 1997;18:49-56. PMID 9055151
53: Moffatt ME, Harlos S, Kirshen AJ, Burd L. Desmopressin acetate and nocturnal enuresis: how much do we know. Pediatrics 1993;92:420-5. PMID 8361796
54: Monda JM, Husmann DA. Primary nocturnal enuresis: a comparison among observation, imipramine, desmopressin acetate and bedwetting alarm systems. J Urol 1995;154:745-8. PMID 7609169
55: Neveus T. The evaluation and treatment of therapy-resistant enuresis: a review. Ups J Med Sci 2006;111(1):61-71. PMID 16553246
56: Neveus T. Diagnosis and management of nocturnal enuresis. Curr Opin Pediatr 2009;21(2):199-202. PMID 19307899
57: Neveus T, Bader G, Sillen U. Enuresis, sleep and desmopressin treatment. Acta Paediatrica 2002;91:1121-5. PMID 12434900
58: Neveus T, Johansson E, Nydahl-Persson K, Peterson H, Hansson S. Diuretic treatment of nocturnal enuresis. Scand J Urol Nephrol 2005;39(6):474-8. PMID 16303723
59: Norgaard JP, Rittig S, Djurhuus JC. Nocturnal enuresis: an approach to treatment based on pathogenesis. J Pediatr 1989;114:705-10. PMID 2926585
60: Ohtomo Y, Umino D, Takada M, Niijima S, Fujinaga S, Shimizu T. Traditional Japanese medicine, yokukansan, for the treatment of nocturnal enuresis in children. Pediatr Int 2013;55(6):737-40. PMID 23773379
61: Oredsson AF, Jorgensen TM. Changes in nocturnal bladder capacity during treatment with the bell and pad for monosymptomatic nocturnal enuresis. J Urol 1998;160:166-9. PMID 9628642
62: Pierce CM, Whitman RM, Mass TW, Gay ML. Enuresis and dreaming. Arch Gen Psychiatry 1961;4:166-70. PMID 13735532
63: Readett DR, Morris JS, Serjeant GR. Nocturnal enuresis in sickle cell haemoglobinopathies. Arch Dis Child 1990;65:290-3. PMID 2334206
64: Robson WL, Jackson HP, Blackhurst D, Leung AK. Enuresis in children with attention-deficit hyperactivity disorder. South Med J 1997;90:503-5. PMID 9160067
65: Robson WL, Norgaard JP, Leung AK. Hyponatremia in patients with nocturnal enuresis treated with DDAVP. Eur J Pediatr 1996;155:959-62. PMID 8911897
66: Rombis V, Triantafyllidis A, Balaxis E, Kalaitzis C, Touloupidis S. Nocturnal enuresis in children. A four-year experience in outpatient clinics of pediatric urology. Folia Med (Plovdiv) 2005;47(2):24-8. PMID 16544846
67: Rona RJ, Li L, Chinn S. Determinants of nocturnal enuresis in England and Scotland in the '90s. Dev Med Child Neurol 1997;39:677-81. PMID 9352729
68: Saettini F, Marra C, Rota M, Liu X, Bower WF. Acupuncture for the treatment of pediatric nocturnal enuresis: a systematic review and a meta-analysis of randomized and non-randomized studies. European Journal of Integrative Medicine 2016;8(2):89-97.
69: Schaumburg HL, Rittig S, Djurhuus JC. No relationship between family history of enuresis and response to desmopressin. J Urology 2001;166:2435-7. PMID 11696806
70: Shreeram S, He JP, Kalaydjian A, Brothers S, Merikangas KR. Prevalence of enuresis and its association with attention-deficit/hyperactivity disorder among U.S. children: results from a nationally representative study. J Am Acad Child Adolesc Psychiatry 2009;48(1):35-41. PMID 19096296
71: Skoog SJ, Stokes A, Turner KL. Oral desmopressin: a randomized double-blind placebo controlled study of effectiveness in children with primary nocturnal enuresis. J Urol 1997;158:1035-40. PMID 9258137
72: Stone J, Malone PS, Atwill D, McGrigor V, Hill CM. Symptoms of sleep-disordered breathing in children with nocturnal enuresis. J Pediatr Urol 2008;4(3):197-202. PMID 18631925
73: Swithinbank LV, Brookes ST, Shepherd AM, Abrams P. The natural history of urinary symptoms during adolescence. Br J Urol 1998;81(Suppl 3):90-3. PMID 9634028
74: Thompson S, Rey JM. Functional enuresis: is desmopressin the answer. J Am Acad Child Adolesc Psychiatry 1995;34:266-71. PMID 7896665
75: Thottam PJ, Kovacevic L, Madgy DN, Abdulhamid I. Sleep architecture parameters that predict postoperative resolution of nocturnal enuresis in children with obstructive sleep apnea. Ann Otol Rhinol Laryngol 2013;122(11):690-4. PMID 24358629
76: Tugtepe H, Thomas DT, Ergun R, et al. The effectiveness of transcutaneous electrical neural stimulation therapy in patients with urinary incontinence resistant to initial medical treatment or biofeedback. J Pediatr Urol 2015;11(3):137.e1-5. PMID 25824876
77: Ulfberg J, Thuman R. A non-urologic cause of nocturia and enuresis--obstructive sleep apnea syndrome (OSAS). Scand J Urol Nephrol 1996;30:135-7. PMID 8738060
78: Vogel W, Young M, Primack W. A survey of physician use of treatment methods for functional enuresis. J Dev Behav Pediatr 1996;17:90-3. PMID 8727842
79: von Gontard A, Hollmann E, Eiberg H, Benden B, Rittig S, Lehmkuhl G. Clinical enuresis phenotypes in familial nocturnal enuresis. Scand J Urol Nephrol 1997(Suppl);183:11-6. PMID 9165597
80: von Gontard A, Schaumburg H, Hollmann E, Eiberg H, Rittig S. The genetics of enuresis: a review. J Urol 2001;166(6):2438-43. PMID 11696807
81: Wang RC, Elkins TP, Keech D, Wauquier A, Hubbard D. Accuracy of clinical evaluation in pediatric obstructive sleep apnea. Otolaryngol Head Neck Surg 1998;118:69-73. PMID 9450831
82: Wei CC, Wan L, Lin WY, Tsai FJ. Rs 6313 polymorphism in 5-hydroxytryptamine receptor 2A gene association with polysymptomatic primary nocturnal enuresis. Journal of Clinical Laboratory Analysis 2010;24:371-5. PMID 21089166
83: Wille S. Nocturnal enuresis: sleep disturbance and behavioural patterns. Acta Paediatr 1994;83:772-4. PMID 7949811
84: Wille S, Anveden I. Social and behavioural perspectives in enuretics, former enuretics and non-enuretic controls. Acta Paediatr 1995;84:37-40. PMID 7734896
85: Williams K, Chambers M, Logan S, Robinson D. Association of common health symptoms with bullying in primary school children. BMJ 1996;313:17-9. PMID 8664762
86: Wolfish NM, Pivik RT, Busby KA. Elevated sleep arousal thresholds in enuretic boys: clinical implications. Acta Paediatr 1997;86:381-4. PMID 9174224
87: Xiang B, Biji S, Liu JX, Chu WC, Yeung DK, Yeung CK. Functional brainstem changes in response to bladder function alteration elicited by surgical reduction in bladder capacity: a functional magnetic resonance imaging study. J Urol 2010;184(5):2186-91. PMID 20850835
88: Yakinci C, Mungen B, Durmaz Y, Balbay D, Karabiber H. Autonomic nervous system functions in children with nocturnal enuresis. Brain Dev 1997;19:485-7. PMID 9408596
89: Yousef KA, Basaleem HO, bin Yahiya MT. Epidemiology of nocturnal enuresis in basic schoolchildren in Aden Governorate, Yemen. Saudi J Kidney Dis Transpl 2011;22(1):167-73. PMID 21196640
90: Zhu J, Arsovska B, Kozovska K. Nocturnal enuresis in children -- treatment with acupuncture. IOSR Journal of Dental and Medical Sciences 2016;15(9):29-31.

Contributors

All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Author

Rosalia C Silvestri MD

Dr. Silvestri, Director of the Sleep Medicine Center at the University of Messina, Department of Clinical and Experimental Medicine, has no relevant financial relationships to disclose.
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Editor

Antonio Culebras MD FAAN FAHA FAASM

Dr. Culebras of SUNY Upstate Medical University at Syracuse has no relevant financial relationships to disclose.
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Former Authors

Michael Aldrich MD (original author) and Stephen H Sheldon DO

Patient Profile

Age range of presentation: 02-05 years

06-12 years

13-18 years
Sex preponderance: male>female, >1:1
Heredity: heredity may be a factor
Population groups selectively affected: none selectively affected
Occupation groups selectively affected: none selectively affected

ICD & OMIM codes

ICD-9: Nocturnal enuresis: 788.36
ICD-10: Enuresis, unspecified: R32
OMIM: Enuresis, nocturnal, 1: %600631

Enuresis, nocturnal, 2: %600808

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Sleep enuresis

Associated Disorders

Asthenia
Attention deficit hyperactivity disorder
Complicated enuresis
Developmental delay
Diabetes insipidus
- Diabetes mellitus
- Eosinophilic cystitis
- Epilepsy with generalized tonic-clonic seizures
- Graves disease
- Mental retardation
- Obstructive sleep apnea syndrome
- Primary enuresis
- Secondary enuresis
- Sickle cell anemia
- Uncomplicated enuresis

Differential Diagnosis

uncomplicated enuresis
mild daytime urinary frequency
complicated enuresis
urinary tract infection
diabetes mellitus
- diabetes insipidus
- epilepsy
- sickle cell anemia
- daytime enuresis
- urination initiation abnormalities
- abnormal urinary flow
- secondary enuresis
- sexual abuse

Also Relevant

Attention deficit hyperactivity disorder
Carbamazepine
Drug-induced sleep disorders
Obstructive sleep apnea
Parasomnias
- Sleep disorders
- Sleep disorders associated with headaches
- Sleeptalking

Clinical Categories

Patient Handouts

Sleep

Web References

Clinical Trials

NIH: Sleep Disorders

Sleep enuresis …

Sleep enuresis

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Diagnostic workup

Management

References

Contributors

Author

Editor

Former Authors

Patient Profile

ICD & OMIM codes

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Also in This Category

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Sleep enuresis

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Diagnostic workup

Management

References

Contributors

Author

Editor

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

NF2-related schwannomatosis

Telehealth and cognitive behavioral therapy for insomnia (CBT-I)

NonREM parasomnias

Breath-holding spells

Neurologic disorders associated with obesity

Hypersomnolence

Acute cerebellar ataxia in children

Headache in children: overview and treatment approaches

This is an article preview.
Start a Free Account
to access the full version.