The brain mechanism of awakening dysfunction in children with primary nocturnal enuresis based on PVT-NAc neural pathway: a resting-state fMRI study.

Primary nocturnal enuresis (PNE) affects children's physical and mental health with a high rate. However, its neural mechanism is still unclear. Studies have found that the paraventricular thalamus (PVT) is among the key brain regions implicated with awakening regulation and its control of the transition between sleep and wakening is dependent on signaling through the PVT-nucleus accumbens (NAc) pathway. So this study analyzed the function of brain regions and their connectivity of PVT and NAc. A total of twenty-six PNE and typically developing (TD) children were involved in the study and the methods of amplitude of low frequency fluctuation (ALFF), degree centrality (DC) and functional connectivity (FC) based on resting-state functional magnetic resonance imaging (rs-fMRI) were used to analyze the brain functions. Results showed that there was no statistical significant difference in ALFF and DC between PNE and TD children in bilateral PVT and NAc. And there was statistical significant difference of the comparison of the FC of left PVT (lPVT) and left NAc (lNAc) between PNE and TD children. Meanwhile, there was negative correlation between awakening score and the FC of rPVT and lNAc, and no obvious correlation between awakening score and the FC of lPVT and lNAc in PNE children. Meanwhile, there was both negative correlation between awakening score and the FC of lPVT, rPTV and lNAc in TD children. Therefore, the FC between rPVT and lNAc was more reliable in assessing the degree of awakening ability in PNE children. This finding could help establish the evaluation index of PNE.

Pathogenesis and brain functional imaging in nocturnal enuresis: A review.

Nocturnal enuresis is a common and distressing developmental disease, which may cause various degrees of psychosocial stress and impairment to self-esteem in affected children as well as agitation to their parents or caregivers. Nevertheless, the etiology and pathogenesis of nocturnal enuresis are not understood. Currently, nocturnal enuresis is generally considered a multifactorial disease associated with a complex interaction of somatic, psychosocial, and environmental factors. A variety of postulations have been proposed to explain the occurrence and progression of nocturnal enuresis, including hereditary aberration, abnormal circadian rhythm of antidiuretic hormone secretion during sleep, bladder dysfunction, abnormal sleep, difficulties in arousal, neuropsychological disorders, and maturational delays of the brain. In recent decades, the introduction of functional neuroimaging technologies has provided new approaches for uncovering the mechanisms underlying nocturnal enuresis. The main neuroimaging modalities have included brain morphometry based on structural magnetic resonance imaging (MRI), task-based and event-related functional MRI (fMRI), and resting-state fMRI. The relevant studies have indicated that nocturnal enuresis is associated with functional and structural alterations of the brain. In this review, we briefly summarized the popular hypotheses regarding the pathogenesis of nocturnal enuresis and the current progress of functional neuroimaging studies in examining the underlying mechanisms thereof.

Uroflowmetry in Non-Monosymptomatic Nocturnal Enuresis in Children of Coastal Region of Croatia.

PURPOSE: The aim of the study was to describe clinical characteristics and bladder assessment in children with Non-Monosymptomatic Nocturnal Enuresis (NMNE) in coastal region of Croatia. MATERIALS AND METHODS: Records on 85 patients with NMNE were retrospectively reviewed. Bladder assessments were performed in all children. In this research we: (i) compare clinical characteristics and features of bladder assessment: uroflowmetry, post void residuals (PVR) and bladder wall thickness between boys and girls with NMNE and we compare (ii) clinical characteristics and bladder assessment between children with primary and secondary NMNE. RESULTS: There were 46 girls and 39 boys. The total of 59 children had primary NMNE and 26 children had secondary NMNE. Uroflow pattern was abnormal in 42% of all children with NMNE. Abnormal uroflow pattern in children with NMNE was more often in girls than in boys (P < 0.05) and in children with secondary than in children with primary NMNE (P < 0.05). Ultrasound evidence of bladder wall thickness was more frequent in boys than in girls. Girls were more likely to have dysfunctional voiding and larger residual urinary volume than boys. CONCLUSIONS: Abnormal uroflow pattern in children with NMNE was more often in girls than boys and in children with secondary than in children with primary NMNE.

Sleep Architecture in Valproate-Induced Nocturnal Enuresis in Primary School and Preschool Children.

Nocturnal enuresis is one of the side effects of valproic acid treatment, and generally underdiagnosed by clinicians. Studies reported that a variable incidence of valproic acid-induced nocturnal enuresis is 2.2% to 24% with unclear explanations of the reasons behind valproic acid-induced nocturnal enuresis. A retrospective study was carried out on 260 children (aged 5-12 years) diagnosed with idiopathic epilepsy, treated with valproic acid to evaluate the nocturnal enuresis secondary to valproic acid, and to discuss the characteristics of their sleep architecture. Nocturnal enuresis was reported in 28 (10.7%) patients after a mean exposure time to valproate of 18.78±8.4 days. Nocturnal enuresis was significantly associated with younger age and serum level of valproate (P = .05). The polysomnographic study suggested that the underlying mechanism may be related to impaired sleep efficiency, frequent arousals, prolonged sleep latency, snoring, or increased sleep depth which may impair a child's ability to awaken to the sense of bladder fullness or contractions.Clinical trial registration: ClinicalTrials.gov identifiers: NCT04191863.

Nocturnal Enuresis in the Adult.

PURPOSE OF REVIEW: The goal of this paper is to describe the pathophysiology of adult nocturnal enuresis and develop a generalized approach for evaluation and treatment. RECENT FINDINGS: Although nocturnal enuresis (NE) impacts a significant proportion of the adult population, research on this topic remains lacking. In the few existing studies, the management strategy is extrapolated from research on pediatric nocturnal enuresis. Furthermore, treatment approaches highlight the importance of identifying risk factors and contributing pathologies. The modern urologist should understand the complexity of this problem and the variety of techniques to evaluate and treat the adult patient with NE. Adult nocturnal enuresis is multifactorial and may have multiple underlying pathologies. A comprehensive workup requires an understanding of the patient's history and symptomatology and the pathophysiologic processes that can occur. Treatment should first target identifiable etiologies, although a generalized algorithm can then be utilized with behavioral and lifestyle modifications, followed by medical therapy. Future studies will provide a better framework for treating this problem.

The clinical features and predictive factors of nocturnal enuresis in adult men.

OBJECTIVES: To characterise the clinical features and to discover predictive factors of adult males with nocturnal enuresis (NE). PATIENTS AND METHODS: A total of 43 eligible adult male patients (mean age was 57.8 years) were recruited prospectively over a 2-year period. After documentation of medical history, lower urinary tract symptoms (LUTS) were assessed using the International Consultation on Incontinence Modular Questionnaire-male LUTS (ICIQ-MLUTS), and a 3-day ICIQ-bladder diary (ICIQ-BD). Video-urodynamic studies (VUDS) were conducted conforming to the International Continence Society standards. Univariate and multivariate linear regressions were performed to determine potential predictive factors. RESULTS: Patients with NE had a variety of LUTS and had a high incidence of obesity and comorbidities. On the ICIQ-BD, NE was associated with nocturnal polyuria (NP), reduced nocturnal bladder capacity (NBC), or a combination of both. Subgroup analysis indicated that patients with more frequent NE had: higher body mass index (BMI); more comorbidities; reduced daytime urinary frequency and urgency quality of life (QoL) sub-scores; and increased stress urinary incontinence (SUI) and nocturnal bedwetting sub-scores. Patients with reduced NBC only, had fewer NE episodes, while patients with NP, or with both NP and reduced NBC were more likely have frequent NE. Multivariate analysis confirmed that: BMI; neurogenic causes; sub-scores of SUI QoL and bedwetting domain; the presence of reduced NBC, and both NP and reduced NBC; and bladder outlet obstruction, were all independent predictive factors for the severity of NE. CONCLUSIONS: NE n the adult male should be systemically assessed and treated, as obesity, neurogenic disorders, excessive urine production, bladder storage and emptying dysfunctions are risk factors. Bladder diaries and VUDS provide valuable information on potential pathophysiological causes, which could assist clinical evaluation and selection of focussed treatment.

The role of sleep in the pathophysiology of nocturnal enuresis.

Nocturnal enuresis (NE) is a common condition affecting 5-10% of all 7-year-old children. NE pathophysiology relies on three main factors, abnormal bladder function, excess urine production during sleep and the inability to awaken to the signals of a full bladder. The aim of this review is to evaluate the connection between sleep and its structure and the pathophysiology of NE. NE often occurs early at night and primarily in sleep stage 2 and "deep sleep". Although sleep stage distribution seems similar between NE and healthy children recent studies indicate differences in sleep microstructure. Several lines of research support the common notion among parents that children with NE are difficult to awaken. Moreover, children with NE and nocturnal polyuria differ in terms of hemodynamics and possibly autonomic activation at night compared to healthy controls and the hypothesis has formed that these changes are attributable to different sleep characteristics. In support of this hypothesis, children with NE often suffer sleep disordered breathing, as well as disturbed sleep due to awakenings and arousals. Periodic limb movements (PLM) have been seen in children with refractory enuresis but the clinical significance remains unclear.

Enuretic children have a higher variability in REM sleep when comparing their sleep parameters with nonenuretic control children using a wearable sleep tracker at home.

PURPOSE: That children with nocturnal enuresis ("bedwetting") are deep sleepers is a fact that their parents often state when asking for advice. However, until today no clear difference in sleep has been observed between children who do and do not wet the bed. This study investigates the difference in sleep parameters and heart rate variability (HRV) between enuretic and control children in their home setting by using a wearable sleep tracker during a long observation period. METHODS: Twenty-one enuretic and 18 control children, aged 6 to 12 years old, slept with a wearable sleep tracker device, a Fitbit Charge 2, for 14 consecutive days. In addition, nocturnal urine production (voided volumes and/or weight of the diaper) were measured. The HRV was calculated using the standard time and frequency domain parameters. The Kruskal-Wallis test was applied to evaluate the differences in the sleep and HRV parameters between both groups. RESULTS: Compared with healthy controls, enuretic children showed a higher standard deviation (P = .0209) of minutes spent in rapid eye movement (REM) sleep among the different nights. In addition, they showed the tendencies to fewer awakenings (P = .1161), although this was not significant. Analyzing the wet nights of the enuretic children, they showed higher autonomic activity, lower sleep efficiency and a higher restlessness compared with their dry nights and to the control group. CONCLUSION: This 2-weeks sleep-study, using a wrist-worn sleep tracker device Fitbit Charge 2, in the normal home environment has shown that enuretic children have a larger variation in their REM sleep and sleepless efficiently during a wet night when compared with non-bedwetting children.

Study on neuropathological mechanisms of primary monosymptomatic nocturnal enuresis in children using cerebral resting-state functional magnetic resonance imaging.

Primary monosymptomatic nocturnal enuresis (PMNE) is a heterogeneous disorder, which remains a difficult condition to manage due to lack of knowledge on the underlying pathophysiological mechanisms. Here we investigated the underlying neuropathological mechanisms of PMNE with functional MRI (fMRI), combining the amplitude of low frequency fluctuation (ALFF), regional homogeneity (ReHo), and seed-based functional connectivity (seed-based FC) analyses. Compared to the control group, PMNE group showed decreased ALFF value in the left medial orbital superior frontal gyrus (Frontal_Med_Orb_L), and increased ReHo value in the left superior occipital gyrus (Occipital_Sup_L). With left thalamus as the seed, PMNE group showed significantly decreased functional connectivity to the left medial superior frontal gyrus (Frontal_Sup_Medial_L). We conclude that these abnormal brain activities are probably important neuropathological mechanisms of PMNE in children. Furthermore, this study facilitated the understanding of underlying pathogenesis of PMNE and may provide an objective basis for the effective treatment.

Urinary and bowel disfunction in autism spectrum disorder: a prospective, observational study.

BACKGROUND: Vesico- sphincter and bowel dysfunction have been frequently detected in Autism spectrum disorder (ASD) patients, but to date no consistent information exist on adults affected by the disease. We evaluated the prevalence and types of bladder and bowel disfunction (BBD) in young and adult patients affected by ASD. SUBJECTS AND METHODS: Twenty- seven adults and 20 children/teens with ASD and a matched group of typically developing subjects were enrolled. Daily pads use and episodes of urinary incontinence (UI) were recorded in a 3- day voiding diary. Patients underwent also the measurement of post-void urinary residual volume and 3- day bowel diary. In addition, type and duration of the pharmacological agents assumed by the patients were accurately recorded. RESULTS: Any type of UI was observed in 85.1% of adults and in 90% of children/teens. In adults, nocturnal enuresis (NE, 62.9%) and diurnal intermittent UI (37%) were the most frequently observed bladder dysfunction while in children/ teens were NE (75%) and diurnal continuous UI (40%). In all patients was demonstrated a significant relationship between urinary symptoms and pharmacological agents, particularly NE and clotiapine (p<0.004) and periciazine (p<0.008). CONCLUSIONS: Young and adult patients with ASD present with a high prevalence of BBD and concomitant antipsychotic medications could to play a contribution in induction and/or maintaining of BBD.

The discrepancy between the uroflowmetry parameters, curve patterns, and lower urinary tract symptoms of children with nocturnal enuresis according to the presence or absence of daytime urinary incontinence.

AIM: To evaluate the uroflowmetry (UFM), which reflects the urinary symptoms of children with nocturnal enuresis (NE). METHODS: This study retrospectively investigated 93 children who underwent UFM three times on the same day (≥8 years old; mean age: 9 years and 10 months; 66 boys and 27 girls). Children with the combination of daytime incontinence (DI) and NE (DI+NE group: n = 45) and NE alone (isolated NE group: n = 48) were compared. UFM curve patterns were classified into five types: bell (B), tower (T), staccato (S), plateau (P), and interrupted (I). An unclassified (U) curve pattern was designated when all three curve patterns differed. Patterns other than the B pattern were considered abnormal (A). Each score in the dysfunctional voiding symptom score (DVSS) was also compared between the two groups. RESULTS: The UFM curve pattern was B (n = 21), T (n = 15), S (n = 4), P (n = 1), U (n = 4) in the DI+NE group and B (n = 25), T (n = 10), S (n = 7), P (n = 2), U (n = 4) in the isolated NE group, indicating no significant difference (B vs A; P = .680). The two items of DVSS questionnaire were significantly greater in the DI+NE group than in the isolated NE group (voiding postponement: 0.93 ± 1.18 vs 0.23 ± 0.56, P = .001, urgency: 2.09 ± 1.06 vs 0.56 ± 0.85, P < .001). CONCLUSION: The abnormal UFM curve patterns did not differ significantly between NE children with and without DI. However, the DVSS questionnaire scores differed significantly. UFM did not reflect the urinary symptoms of children with NE.

Bladder and bowel dysfunction, adaptive behaviour and psychiatric profiles in adults affected by autism spectrum disorders.

AIMS: Bladder and bowel dysfunction (BBD) have been recognized in children affected by autism spectrum disorder (ASD), but no consistent information exist in adults with the condition. We evaluated the prevalence of BBD and the impact of psychiatric and behavioural profiles in adults affected by ASD. METHODS: Twenty-two adults and 13 children/teens with ASD and a matched group of typically developing subjects (TD) were prospectively studied. Patients and TD subjects underwent the evaluation of urinary incontinence (UI: diurnal, continuous or intermittent), nocturnal enuresis (NE), and bowel disturbances with the 3-day voiding and bowel diary. In addition, assessment of intellectual disability (ID) and psychiatric and adaptive behaviours with the Neuropsychiatric Inventory Scale (NPI) and the Vineland Adaptive Behaviour Scale 2nd Edition (Vineland-II), was performed. RESULTS: In adults, any type of incontinence was observed in 81.8% of cases, and NE and intermittent UI in 59.0% and 36.3% of patients, respectively. Faecal incontinence and constipation were detected 36.3% and in 68.1% of cases, respectively. ID was severe in 2 cases and profound in 18; NPI and Vineland-II items most affected were "Irritability/Lability," "Motor Activity," and "Agitation," and IQ-Socialization and IQ-Communication. Significant relationships were identified between intermittent UI and greater ID (P < .02) and high "anxiety" (P < .05), and between NE and high "euphoria/elevated mood" (P < .05). These results were similar to those observed in children/teens. CONCLUSIONS: Adults with ASD, and greater ID and mood disorders, present with a high prevalence of BBD. A shared pathogenetic mechanism could underlie the co-occurrence of ASD, mood disorders, and BBD.

Pelvic floor muscle training alone or in combination with oxybutynin in treatment of nonmonosymptomatic enuresis. A randomized controlled trial with 2-year follow up.

OBJECTIVE: To compare the results of the standard urotherapy alone and associated with pelvic floor muscle training alone, and in combination with oxybutynin in treatment of nonmonosymptomatic nocturnal enuresis. METHODS: A total of 38 children aged 5 to 10 years were randomized into three groups: Group I (n=12) that was submitted to standard urotherapy; Group II (n=15), standard urotherapy associated with pelvic floor muscle training; and Group III (n=11), standard urotherapy associated with pelvic floor muscle training and oxybutynin; the treatment lasted 12 weeks. The assessment tools used were playful bladder diary, and a 48-hour bladder diary, before and after treatment. After 2 years, patients were assessed by telephone using a standardized questionnaire. RESULTS: The data of children from the three groups were homogeneous at baseline. After 12-week treatment, all children showed improved symptoms and signs of nonmonosymptomatic nocturnal enuresis, but the differences were not significant among the groups. After 2 years, the three groups showed maintenance of treatment results, but no differences among them. CONCLUSION: All treatment modalities were effective regarding improved enuresis and lower urinary tract symptoms, but the sample was not large enough to show differences among groups.

Assessment of serum levels of copeptin and corticotropin-releasing factor in children with monosymptomatic and non-monosymptomatic nocturnal enuresis.

BACKGROUND: Nocturnal enuresis is defined as bed-wetting in children from the age of five years that occurs during sleep; if untreated, the condition can result in social and psychological problems both for the children and their parents. Nocturnal enuresis is a complicated disease that includes multiple pathogenetic factors. Nocturnal enuresis is divided into two subgroups: monosymptomatic and non-monosymptomatic. The role of some biomarkers in patients with monosymptomatic enuresis has been reported in a small number of the studies. OBJECTIVE: The aim of this research was to evaluate the serum levels of copeptin and corticotropin-releasing factor (CRF) in monosymptomatic and non-monosymptomatic nocturnal enuresis cases. Although these markers were previously examined in children with monosymptomatic enuresis, there is no study that has evaluated these markers in non-monosymptomatic children. STUDY DESIGN: One hundred nineteen children with nocturnal enuresis (5-16 years) and forty healthy children (5-17 years) were enrolled to the study. Of the nocturnal enuresis group, forty-nine were monosymptomatic and seventy were non-monosymptomatic. Copeptin and CRF were measured by a competitive inhibition method with enzyme-linked immunosorbent assay. RESULTS: The serum copeptin levels were significantly lower in children with monosymptomatic and non-monosymptomatic nocturnal enuresis than in the controls.(median, 34.7 [interquartile range (IQR): 34 pg/ml], 39.8 [IQR: 29 pg/ml] vs 52.1 [IQR: 14 pg/ml], respectively, P < 0.05). The serum CRF levels were significantly lower in children with monosymptomatic and non-monosymptomatic nocturnal enuresis than in the controls (median, 35.1 [IQR: 19 pg/ml], 34.05 [IQR: 24 pg/ml] vs 78.3 [IQR: 39 pg/ml], respectively, P < 0.05). There was no significant difference in copeptin and CRF levels between the children with monosymptomatic and non-monosymptomatic nocturnal enuresis. DISCUSSION: Copeptin is presumed to be a sensitive surrogate biomarker for arginine vasopressin release. To date, there are only two studies in the literature that assess the relationship between copeptin and monosymptomatic enuresis. The only study in the literature demonstrated significantly decreased levels of CRF in monosymptomatic enuretic children. It was demonstrated that the levels of copeptin and CRF differ in both children with monosymptomatic and non-monosymptomatic nocturnal enuresis from the control groups. It was also demonstrated that copeptin and CRF levels were not different between the children in monosymptomatic and non-monosymptomatic groups. CONCLUSION: Those changes in both copeptin and CRF which were shown in this study in monosymptomatic and non-monosymptomatic enuretic children may contribute to the pathogenesis of nocturnal enuresis. Further case-control studies can evaluate the copeptin and CRF levels before treatments in monosymptomatic and non-monosymptomatic patients to decide potential effectiveness of treatment.

Night-time diuresis pattern in children with and without primary monosymptomatic nocturnal enuresis.

INTRODUCTION: Night-time polyuria as the dominating pathophysiological mechanism for primary monosymptomatic nocturnal enuresis (PMNE) has been put in question with nocturnal detrusor overactivity and high arousal thresholds as alternatives. An earlier finding of night-time polyuria in 12% of healthy non-enuretic schoolchildren underscores that excessive night-time diuresis per se is unlikely the major cause of PMNE. OBJECTIVE: The objective of this study was to compare the night-time diuresis pattern in children with and without PMNE and to evaluate the role of night-time polyuria in provoking enuretic episodes in children with PMNE. STUDY DESIGN: Night-time diuresis pattern was recorded in 27 children with PMNE, aged 6-15 years, and 29 non-enuretic children, aged 6-13 years. Using a portable ultrasound recorder, the bladder volume was estimated at 15-min intervals for at least three nights with the child sleeping in its own bed at home. The volume of enuretic episodes was controlled using preweighed diapers. All voids were registered by time and volume. Diuresis during night time was estimated from the slope of regression lines fitted to ultrasound recording points. Mean night-time diuresis was calculated from total urine production during the night and time interval from the last void before bedtime to the first morning void. RESULTS: Night-time bladder filling pattern was recorded from 189 nights, giving 149 interpretable patterns for analysis (77 children with PMNE and 72 dry children). The night-time diuresis pattern was similar for children with or without PMNE, showing large variability between different nights of the same child. Most nights displayed a smooth bladder filling at constant low rate, whereas other nights showed an early phase with high diuresis followed by a longer period of low diuresis with no difference between the two groups. DISCUSSION: Night-time diuresis has been non-invasively monitored in children while asleep in their own beds at home. The pattern of night-time diuresis varies considerably between different nights of the same child, with no obvious differences in any diuresis parameters between children with or without PMNE. CONCLUSION: Non-enuretic children have similar diuresis pattern and maximal night-time diuresis values as children with PMNE, making it unlikely that PMNE is caused by night-time polyuria per se (Summary figure). Delayed maturation of sleep mechanisms such as decreased arousability or sleep inhibition of the micturition reflex is more likely to be the main etiology for enuresis.

Nocturnal enuresis in children is associated with differences in autonomic control.

STUDY OBJECTIVES: To assess the relationship between urine osmolality, cardiovascular parameters, and nocturnal enuresis in a population of children undergoing polysomnographic assessment. METHODS: This prospective observational study included consecutive children aged 5-17 years presenting for overnight polysomnography. Children were evaluated using continuous ambulatory blood pressure monitoring to assess heart rate and blood pressure. Urine samples were collected throughout the night to determine urine sodium excretion and osmolality. Comparisons of results were made between children with and without a history of nocturnal enuresis. RESULTS: A total of 61 children were included for analysis; 13 had a history of nocturnal enuresis. Children with nocturnal enuresis had greater disruption in respiratory parameters including higher apnea-hypopnea index (mean difference 12.2 ± 8.8 events/h, p < 0.05), attributable to more central respiratory events (mean difference 5.4 ± 4.9, p < 0.05), and higher variability in both oxygen and carbon dioxide parameters compared to those without nocturnal enuresis. Sleep parameters, urine osmolality, and blood pressure did not differ between groups. Children with nocturnal enuresis showed an increase, rather than a decrease, in heart rate across the night (+5.4 ± 19.1 vs. -6.0 ± 14.8 beats/min, p < 0.05). CONCLUSIONS: Children with a history of nocturnal enuresis have greater respiratory abnormalities, no differences in urine osmolality or blood pressure, and loss of normal heart rate decrease across the night. This pattern suggests that autonomic control, rather than renal or hemodynamic abnormalities, may contribute to the pathophysiology of nocturnal enuresis.

Comparison of desmopressin, alarm, desmopressin plus alarm, and desmopressin plus anticholinergic agents in the management of paediatric monosymptomatic nocturnal enuresis: a network meta-analysis.

OBJECTIVE: To assess the efficacy of desmopressin, alarm, desmopressin plus alarm, and desmopressin plus anticholinergic agent (AA) therapy in the management of paediatric monosymptomatic nocturnal enuresis (MNE) using a network meta-analysis. MATERIALS AND METHODS: We searched the electronic databases PubMed, Cochrane Library, EMBASE and Web of Science from inception to 1 March 2018. Randomized controlled trials (RCTs) that compared desmopressin, alarm, desmopressin plus alarm, and desmopressin plus AAs were identified. The network meta-analysis was conducted with software R 3.3.2 and STATA 14.0. RESULTS: Eighteen RCTs with a total of 1 649 participants were included. The meta-analysis results showed that complete response (CR) and success rates with desmopressin plus AAs were higher than with desmopressin or alarm monotherapy. Success rates for desmopressin plus alarm therapy were higher than for alarm monotherapy. No obvious difference was observed between desmopressin plus AAs and desmopressin plus alarm therapy with regard to CR rate and success rate. The relapse rate with alarm monotherapy was much lower than with desmopressin monotherapy. Adverse events seemed to be infrequently and tolerable for all treatments. The ranking probability results were as follows: desmopressin plus AA ranked first for the outcomes of CR and success, desmopressin plus alarm therapy ranked first for mean number of wet nights per week, and alarm therapy had the lowest relapse rate. CONCLUSIONS: The network meta-analysis showed that desmopressin had similar efficacy to alarm therapy but a higher relapse rate. Desmopressin plus AA therapy was associated with better efficacy than and a similar relapse rate to desmopressin monotherapy. Desmopressin plus alarm therapy was similar to both desmopressin and alarm monotherapy in efficacy. All treatments, including desmopressin plus AAwere associated with tolerable adverse events; however, additional high-quality studies are needed for further evaluation of these treatments.

Pelvic floor muscle training alone or in combination with oxybutynin in treatment of nonmonosymptomatic enuresis. A randomized controlled trial with 2-year follow up / Exercícios dos músculos do assoalho pélvico exclusivos ou em combinação com oxibutinina no tratamento da enurese não monossintomática. Um estudo randomizado controlado com 2 anos de seguimento

Abstract Objective To compare the results of the standard urotherapy alone and associated with pelvic floor muscle training alone, and in combination with oxybutynin in treatment of nonmonosymptomatic nocturnal enuresis. Methods A total of 38 children aged 5 to 10 years were randomized into three groups: Group I (n=12) that was submitted to standard urotherapy; Group II (n=15), standard urotherapy associated with pelvic floor muscle training; and Group III (n=11), standard urotherapy associated with pelvic floor muscle training and oxybutynin; the treatment lasted 12 weeks. The assessment tools used were playful bladder diary, and a 48-hour bladder diary, before and after treatment. After 2 years, patients were assessed by telephone using a standardized questionnaire. Results The data of children from the three groups were homogeneous at baseline. After 12-week treatment, all children showed improved symptoms and signs of nonmonosymptomatic nocturnal enuresis, but the differences were not significant among the groups. After 2 years, the three groups showed maintenance of treatment results, but no differences among them. Conclusion All treatment modalities were effective regarding improved enuresis and lower urinary tract symptoms, but the sample was not large enough to show differences among groups.

Resumo Objetivo Comparar os resultados da uroterapia padrão isolada e associada ao treinamento dos músculos do assoalho pélvico isoladamente e em combinação com a oxibutinina no tratamento da enurese noturna não monossintomática. Métodos Trinta e oito crianças entre 5 e 10 anos de idade foram randomizadas em três grupos: Grupo I (n=12) realizou uroterapia padrão; Grupo II (n=15) realizou uroterapia padrão associada ao treinamento muscular do assoalho pélvico; e Grupo III (n=11) realizou uroterapia padrão associada ao treinamento muscular do assoalho pélvico e oxibutinina. O tratamento teve duração de 12 semanas. Os instrumentos de avaliação foram diário miccional lúdico e diário miccional de 48 horas, antes e depois do tratamento. Após 2 anos, os pacientes foram avaliados por telefone, usando um questionário padronizado. Resultados Os dados das crianças dos três grupos eram homogêneos no início do estudo. Após 12 semanas de tratamento, todas as crianças apresentaram melhora em relação aos sinais e sintomas de enurese noturna não monossintomática, mas as diferenças não foram significativas entre os grupos. Depois de 2 anos, os resultados do tratamento se mantiveram nos três grupos, mas não houve diferenças entre os grupos. Conclusão As três modalidades de tratamento foram eficazes na melhora da enurese e dos sintomas do trato urinário inferior, mas o tamanho da amostra não foi grande o suficiente para mostrar diferenças entre os grupos.

Frequency and features of nocturnal enuresis in Pakistani children aged 5 to 16 years based on ICCS criteria: a multi-center cross-sectional study from Karachi, Pakistan.

BACKGROUND: Nocturnal enuresis (NE) is a common symptom in children worldwide. International Children's Continence Society (ICCS) defines enuresis as either mono-symptomatic, NE with lower urinary tract symptoms and NE with co-morbid conditions. The objectives of this study were to determine the frequencies and types of NE and associated symptoms and conditions in children aged 5 to 16 years based on ICCS criteria. METHODS: A multi-center cross sectional study was conducted between November 2012 and December 2013 in the primary care clinics of four hospitals in Karachi. Children aged five to fifteen years were included through consecutive sampling. Informed consent was obtained from the parents and a pre-coded semi-structured questionnaire was used to obtain the information. Data was entered on SPSS version 20.0 and multivariable logistic regression analysis was used for data analysis. RESULTS: Out of 429 children aged between five and sixteen years, 243(56.9%) were boys and the remaining 186(43.1%) were girls. One hundred and eighty three children (43%) had nocturnal enuresis (NE). Forty four (10.3%), had mono-symptomatic NE, 57(31.1%) had associated lower urinary tract symptoms (NE-LUTS), whereas 30 (16.3%) had NE with a co-morbid condition. Fifty two (28.4%) NE's had at least one of both LUTS and a co-morbid condition. Out of the 246(57%) non-enuretic's, 31(12.6%) had a LUTS, 95(38.6%) had a co-morbid condition and 57(23.2%) had at least one of both LUTS and a co-morbid condition. The remaining 63 (25.6%) were symptom free. Increased voiding frequency, urgency, dysuria, suprapubic pain and daytime incontinence were the LUTS significantly associated with NE. Co-morbid conditions significantly associated with NE included constipation, congenital defects, developmental delay, and learning and sleep problems. CONCLUSION: Although NE can be an only symptom, it is often associated with lower urinary tract symptoms like dysuria, urgency, suprapubic pain, and daytime incontinence. Children presenting with NE often have co-morbid conditions like constipation, urinary tract infection, sleep disorders, and developmental delay. Many children presenting with these conditions as the primary complaint may also have NE. It should be addressed as unrecognized and untreated NE can cause additional morbidity and distress.