Is Lack of Bladder Inhibition during Sleep a Mechanism of Nocturnal Enuresis?
Article Outline
Abbreviations: dDAVP, Desmopressin, V2, Vasopressin type 2
Monosymptomatic nocturnal enuresis, defined as bedwetting without daytime bladder symptoms, affects 6% to 10% of children at age 7, an age at which social consequences and family frustration are often increasingly problematic. Although spontaneous resolution occurs at a rate of 15% per year, the prevalence of nocturnal enuresis in adults remains 0.5%. This common diagnosis may affect self-esteem and social interactions.
See related articles, p 571 and p 575
The evaluation of enuretic children has documented smaller maximal bladder capacities and lower levels of nocturnal vasopressin secretion, suggesting an imbalance between bladder size and urine volume as the etiology of bedwetting. Treatment with desmopressin (dDAVP), an analog of vasopressin, to decrease urine output overnight is immediately but temporarily effective in decreasing wet nights, and enuresis alarms are slowly but persistently effective in decreasing wet nights. Furthermore, as children achieve dry nights with the alarm, maximal bladder capacity increases. The improvements seen with dDAVP and with alarms reinforced the thinking that the mechanism of nocturnal enuresis is an imbalance between nocturnal urine volume and bladder capacity. Two reports in this issue of The Journal expand our understanding by supporting a role of the central regulation of nighttime bladder function.
Van Hoeck et al1 measured voided volumes, including bedwetting volumes, for 48 hours in 76 children with and 50 children without monosymptomatic nocturnal enuresis. The calculated urine output rate followed a circadian rhythm and did not differ in the 2 groups of children. Few overnight urine volumes met the criterion for nocturnal polyuria defined by the International Children’s Continence Society as the sum of all voidings after bedtime and the first morning void > 1.3(30x + 30), where x = age in years. Maximal voided volume was almost always the first morning void after a dry night. Bladder capacity, as measured by bladder-holding exercises during the day, was no different between children who wet the bed and those who did not. Daytime voided volumes as recorded in a voiding diary were no different between children with and without nocturnal enuresis. Bedwetting volumes were similar to daytime voided volumes. The difference in children who were dry overnight was a longer bladder filling time. Bedwetting appears to occur from a shorter bladder filling time during sleep, and the findings suggest a defect in the circadian rhythm of detrusor inhibition as a cause of the aborted bladder filling.1
How then does dDAVP decrease bedwetting events if aborted bladder filling rather than polyuria is the cause of nocturnal enuresis? Evidence for a central action of dDAVP comes from Iwasaki et al,2 who used a rat model to demonstrate that administration of dDAVP by the intravenous or intracerebroventricular route affects bladder-related neurons in a way that tends to suppress bladder activity. Further support for extrarenal effects of dDAVP comes from a case report of a child with nephrogenic diabetes insipidus (abnormal vasopressin type 2 [V2] receptor) and nocturnal enuresis whose enuresis was converted to nocturia on repeated trials when given dDAVP.3 dDAVP or desmopressin is known to stimulate the V2 or renal receptor, but it also appears to be a potent stimulator of the human vasopressin type 1b receptor in the pituitary.4
Schulz-Juergensen et al5 present evidence for a central action of dDAVP in children with monosymptomatic nocturnal enuresis. Children with nocturnal enuresis have less ability to inhibit muscle contraction in response to startle stimuli. Treatment with dDAVP restores this desensitization to startle. The children who had a good clinical response to dDAVP were significantly more likely to normalize the response to startle. A follow-up study of startle inhibition in these children after attainment of nocturnal continence off dDAVP might reinforce the relevance of this mechanism.
If dDAVP facilitates nocturnal continence through central bladder inhibition, then what are the morning urine volumes after a dry night? Maximal bladder capacity is usually the first morning void after a dry night in continent children.1 Finding a larger first morning-voided volume than the usual bedwetting volume or daytime voided volume after a dry night with dDAVP would suggest that dDAVP is effective not just by decreasing urine volume through V2 receptors in the kidney. Inadequate dDAVP at night may be one mechanism for aborted bladder filling through central receptors.
Monosymptomatic nocturnal enuresis continues to be an enigma. Several pathways may lead to the common endpoint of nocturnal enuresis, and the key will be developing strategies to help better understand and individualize care.6
References
- Urine output rate and maximum voided volume in school-age children with and without nocturnal enuresis. J Pediatr. 2007;151:575–580
- Modulation by desmopressin of neuronal activity in the brainstem micturition center. Urology. 2004;63:994–998
- . Relief of nocturnal enuresis by desmopressin is kidney- and vasopressin type 2 receptor–independent. J Am Soc Nephrol. 2007;18:1534–1539
- . 1-Desamino-8-D-arginine vasopressin (DDAVP) as an agonist on V1b vasopressin receptor. Biochem Pharmacol. 1997;53:1711–1717
- . Effect of dDAVP on prepulse inhibition of startle supports a central etiology of primary monosymptomatic enuresis. J Pediatr. 2007;151:571–574
- Nocturnal enuresis: an international evidence-based management strategy. J Urol. 2004;171:2545–2561
PII: S0022-3476(07)00651-8
doi:10.1016/j.jpeds.2007.06.044
© 2007 Mosby, Inc. All rights reserved.
Refers to article:
- Effect of 1-Desamino-8-D-Arginine Vasopressin on Prepulse Inhibition of Startle Supports a Central Etiology of Primary Monosymptomatic Enuresis , 10 October 2007
- Urine Output Rate and Maximum Volume Voided in School-Age Children with and without Nocturnal Enuresis , 08 October 2007
