The immaturity of the central nervous system and nocturnal polyuria involved in the pathogenesis of nocturnal enuresis are expressed through detrusor hyperactivity and arousal disorders, which results in the inability to awaken and control urination at night , thus being current research they use diagnostic methods in an attempt to elucidate the involvement of the central nervous system . Objective: This review aims to systematically analyze the available literature on changes in neural circuits ascertained in nocturnal enuresis.

Following the recommendations of the PRISMA guide ( Preferred Reporting Items for Systematic Reviews and Meta- Analyzes ), the bibliographic search was performed on the PubMed and BIREME platforms and in the MEDLINE and LILACS databases .

Articles published in the twenty-year period were included, whose focus was to investigate changes in the nervous system in children with enuresis, in the languages: English, Portuguese and Spanish, excluding literature reviews, dissertations, manuscripts that did not clearly report the changes observed in the central nervous system, dissertations, editorials, articles published with the adult population, pilot studies, duplicate publication, articles that did not contain a summary and case report , using the descriptors: brain ; nervous system; nocturnal enuresis ; neural pathways ; neurodevelopmental disorders , and the crossings performed through the Boolean operator AND.  

 The quality analysis of the selected studies received scores to enable the identification of methodological quality through the Dows and Black scale . The studies were identified and read by two researchers independently , whereas , any disagreement between the reviewers were resolved through discussion and consensus and when needed was ordered to participate and study the judgment of a third reviewer .

Of the 1,046 studies found, eleven were selected, nine of which were conducted in China and two in Germany , covering a total of 690 patients aged between 5 and 16 years, with 369 children with enuresis and 351 children without voiding changes, all of whom were the studies observational cross-sectional analysis .
 A predominance of males was found among individuals who suffer from enuresis (n = 229), representing 62% of the children in the study with this condition , of whom used electrophysiological studies and structural and functional magnetic resonance imaging. 
Among the studies requested for the present review , five were composed of children with primary enuresis , one study by monosymptomatic enuresis , four primary monosymptomatic studies and one did not specify. In clinical practice, differentiation is rational to outline the appropriate therapy . 
According to the results reported in these studies, enuretic children present maturational delay in neuronal circuits, specifically in the frontal lobe, thalamus, insula, parietal lobe, cingulate cortex, brain stem and cerebellum, when compared to children with typical development.

This is the first study that we are aware of to contextualize the alterations in neural circuits in nocturnal enuresis in a systematic review. As already reported, there is a correlation of enuresis in psychiatric disorders, in these cases this factor should be addressed initially. As for the management of non- monosymptomatic enuresis , it is essential to manage daytime symptoms, since the failure rate is high and generates a high degree of frustration on the part of caregivers, contributing to the emergence of secondary problems (1).  

  The term minimal brain dysfunction was used to describe the degree of maturational delay in children with this condition, which implies delayed motor development, which could be improved with specific rehabilitation programs (2). Physiotherapy is an ally in the treatment of enuresis, through a careful evaluation, based on functionality, with a focus on sensory integration, stability of the pelvis and trunk, seeking support and muscle synergy, would have a direct influence on the lower urinary tract (4). 

Thus, a multidisciplinary approach is necessary since 1-2% of adolescents remain affected by enuresis, in these cases the symptoms become more severe and frequent and in adulthood persistent enuresis was associated with a lower level of education, a higher rate depression, lower self-esteem, absences from work and social activities (3).

Conclusion: Our study suggests that enuresis is not as benign as has already been reported, and children with this condition have immaturity / dysfunction of neural circuits, which influence n arousal disorder, considering it to be the key to the pathogenesis of nocturnal enuresis . Understanding the etiology could encourage new lines of thought and treatment.

Van Herzeele C, Dhondt K, Roels SP, Raes A, Hoebeke P, Groen L-A, et al. Desmopressin (melt) therapy in children with monosymptomatic nocturnal enuresis and nocturnal polyuria results in improved neuropsychological functioning and sleep. Pediatr Nephrol. 2016 Sep;31(9):1477–84.
Esposito M, Gallai B, Parisi L, Roccella M, Marotta R, Lavano SM, et al. Visuomotor competencies and primary monosymptomatic nocturnal enuresis in prepubertal aged children. Neuropsychiatr Dis Treat. 2013 Jun 26;9:921–6.
von Gontard A, Cardozo L, Rantell A, Djurhuus J-C. Adolescents with nocturnal enuresis and daytime urinary incontinence-How can pediatric and adult care be improved-ICI-RS 2015? Neurourol Urodyn. 2017 Apr;36(4):843–9.