The role of the autonomic nervous system in nocturnal enuresis

Introduction: Nocturnal enuresis (NE) is common in children, but its pathophysiology is still not fully understood. Despite the recognition of three major pathways, nocturnal polyuria, nocturnal bladder dysfunction and sleep disorders, their inter-relations remain elusive. The autonomic nervous system (ANS) which is greatly involved in both diuresis and sleep might have an important role in NE.

Methods: A comprehensive electronic search of Medline database was performed, to identify articles reporting on the role of the autonomic nervous system (ANS) in enuretic children regarding sleep regulation, cardiovascular function and diuresis-related hormones and neurotransmitters.

Results: Of an initial total of 646 articles, 45 studies were finally selected for data extraction according to inclusion criteria, published between 1960 and 2022. Of these studies 26 reported on sleep regulation, 10 on cardiovascular functions and 12 on ANS-associated hormones and neurotransmitters. Evidence on parasympathetic or sympathetic overstimulation in enuretic individuals is suggesting that NE could be attributed to a dysregulation of ANS. Sleep studies have shown increased rapid eye movement sleep time in polyuric enuretic children pointing to sympathetic overactivity, whereas patients with overactive bladder have non-rapid eye movement related enuretic episodes, potentially associated with parasympathetic stimulation. Twenty-four-hour blood pressure monitoring demonstrated "non-dipping" phenomenon, suggesting sympathetic involvement, whereas heart-rate analysis showed parasympathetic hyperfunction. Nocturnal lower levels of arginine-vasopressin, angiotensin II and aldosterone in polyuric children with NE as compared to non-polyuric and controls and potential involvement of dopamine and serotonin in sleep and micturition suggest that ANS-associated hormones and neurotransmitters have a role in the pathogenesis of NE.

Conclusion: Summarizing the existing data we suggest that ANS dysregulation related either with sympathetic or parasympathetic overactivity may provide a unifying model in understanding the pathogenesis of NE in different enuretic subpopulations. This observation provides new insights in future research and new potential treatment options.