Lower Urinary Tract Symptoms In Children Research Articles

Alteration in Mechanical Compliance via Mast Cell Activation in Juvenile and Adult Urinary Bladder

Balance between bladder wall stiffness and mechanical compliance is essential to maintain normal bladder function. These biomechanical properties are directly influenced by the integrity of the extracellular matrix (ECM) and its interaction with urinary bladder smooth muscle (UBSM). While it is clear that normal storage and voiding functions differ between juveniles and adults, it is unclear if these differences are due solely to increases in bladder size. Differences in the mechanical properties of the wall may also exist and are unexplored. Changes in mechanical compliance are implicated in the pathophysiology of many lower urinary tract symptoms (LUTS) such as overactivity and fibrosis due to inflammation. Interestingly, juvenile bladders are particularly susceptible to inflammatory LUTS by various factors (e.g., early life stress) compared to their adult counterparts. We were interested in how bladders from juvenile and adult mice respond to inflammation, specifically driven by mast cell degranulation. We hypothesized that: (1) juvenile bladders are inherently more compliant than adult bladders and (2) mast cell degranulation increases mechanical compliance in both juvenile and adult mouse bladders.Whole mouse bladders from juvenile (4–5 weeks old) and adult (12–14 weeks old) C57Bl/6 male mice were dissected and mounted in a custom designed pentaplanar reflected image macroscopy (PRIM) system for simultaneous measurement of transient pressure events, intravesical pressure, bladder volume, wall stress, and wall stretch during ex vivo bladder filling. Mechanical properties of the bladder wall were measured as the relationship between mechanical stress versus stretch. Properties of the transient contractions were calculated using acquired pressure-volume curves. Measurements were performed in the absence or presence of the mast cell activator Compound 48/80 (10 μg/mL).In the absence of Compound 48/80, the average stress-stretch curves had no significant shift for adult mice compared to young mice, implying no changes in mechanical compliance. However, the mechanical stress in adult mouse bladders was higher compared to juvenile bladders, implying that adult bladders were stiffer. In presence of Compound 48/80, both age groups show similar effects. Mechanical compliance increased with a paradoxical increase in amplitude of transient contractions. Together, these data suggest that while juvenile mouse bladders are less stiff, they respond to mast cell activation in a similar manner as adult bladders. Consequently, rapid degranulation of mast cells in juvenile bladders leads to increased mechanical compliance and contractility. Thus, preventing mast cell degranulation could represent a viable target for treating LUTS in children as well as adults. R01-DK119615 (NRT) and P20-DK127554 (SR and NRT) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

From Clinical Scenarios to the Management of Lower Urinary Tract Symptoms in Children: A Focus for the General Pediatrician.

Lower urinary tract symptoms (LUTS) are a relevant problem in the pediatric population, having a very high prevalence. Diurnal incontinence and nocturnal enuresis are surely the most frequent symptoms, presenting, respectively, in up to 30% of school-age children and up to 10% of children between 6 and 7 years. Stypsis is the most common comorbidity, and it must be considered in the management of LUTS; indeed, the treatment of constipation is curative in most cases for both incontinence and enuresis. The presence or absence of diurnal symptoms in nocturnal enuresis and urgency in diurnal incontinence helps in the differential diagnosis. Urotherapy is always the first-line treatment, while oxybutynin and desmopressin (where appropriate) may help if the first-line treatment is unsuccessful. It is essential to identify conditions that are potentially dangerous for kidney and urinary tract well-being, for which LUTS can be the first manifestation. Starting from a series of clinical scenarios, we will underline the diagnostic clues behind LUTS in children and we will summarize clinical and surgical approaches for the proper management of these conditions.

Prevalence of Lower Urinary Tract Symptoms in Children with Attention-Deficit/Hyperactivity Disorder: Comparison of Hospital and Population-Based Cohorts of 13,000 Patients.

Background: This study investigates the prevalence of lower urinary tract symptoms (LUTS) in school-age children with Attention-Deficit/Hyperactivity Disorder (ADHD) based on hospital-based and population-based cohorts. Methods: The hospital-based sample comprised 42 children with ADHD and 65 without ADHD aged 6-12 years. Voiding dysfunction was assessed by the Dysfunctional Voiding Scoring System (DVSS) questionnaire. We compared the baseline data, DVSS score, and uroflowmetry between the two groups. For the population-based cohort in the national insurance database, we included 6526 children aged 6-12 years, whose claims record included the diagnosis of ADHD, and another 6526 control subjects matched by gender and age. We compared the presence of LUTS diagnosis codes between the two groups. Results: Our results showed that, for the hospital-based cohort, the mean total DVSS score and the proportion of significant LUTS in children in the ADHD group were significantly higher than in subjects in the non-ADHD group. The DVSS subscales showed that the item "I cannot wait when I have to pee" item was significantly higher in the ADHD group (1.62 ± 1.17 vs. 0.90 ± 1.09, p = 0.002). For the population-based cohort, children with ADHD had a significantly higher likelihood of storage symptoms (5.53% vs. 2.91%, p < 0.001) and enuresis (3.28% vs. 1.95%, p < 0.001) compared with those of the no ADHD group. Conclusions: Children with ADHD have a higher prevalence of significant LUTS, especially storage symptoms and enuresis, than children without ADHD. The observed correlations between ADHD and LUTS provided the supporting evidence to evaluate the concomitant voiding dysfunction in children with ADHD.

Dysfunctional Voiding and Incontinence Scoring System for Children and Adolescents: A Tool to Predict Clinical Course and Outcome.

Lower urinary tract symptoms (LUTS) in children are common. In 2005, Akbal et al published the dysfunctional voiding and incontinence scoring system (DVAISS) to assess patient's symptoms. Our study aimed to determine the value of this scoring system for predicting the severity and clinical course of voiding abnormalities in children and adolescents. Patients' symptoms were scored using the DVAISS in children and adolescents with LUTS presenting for the first time to our pediatric urology department between January 2010 and December 2015. We correlated the calculated score with voiding volume, clinical course, and outcome. A total of 168 patients (113 boys, 55 girls; age 5-18 years) with isolated LUTS were included. In 53 patients (group 1), the DVAISS score was less than or equal to 8.5 and in the other 115 patients (group 2), the score was greater than 8.5 suggestive for relevant voiding abnormalities. Patients in group 1 showed a significantly higher average voiding volume (200 vs. 110 mL, p = 0.001). The median time for symptom resolution was significantly higher in group 2 than group 1 (14 vs. 8 months; p = 0.018). The severity of LUTS could be determined by these parameters. Based on the DVAISS, a prediction of the clinical course and approximate treatment duration is possible. Therefore, the DVAISS is useful to assess LUTS in children and is also a valuable tool in rating the severity of the disease. It is also a quite precise predictor of the time needed to resolve the symptoms.

Systematic review and meta-analysis: relationships between attention-deficit/hyperactivity disorder and urinary symptoms in children.

Lower urinary tract symptoms (LUTS), e.g., urinary frequency, pressure, urgency, and overactive bladder syndrome, are commonly reported in children with attention-deficit/hyperactivity disorder (ADHD). Understanding the co-occurrence of these conditions has implications regarding clinical approaches, treatments, and improved quality of life. We conducted a systematic review and meta-analysis to examine the relationships between LUTS and ADHD in children. We searched for articles published between January 1990 and July 2019, in PubMed, CENTRAL, and PsycNet. Two authors independently screened all articles and extracted data. We performed random-effect meta-analyses for ADHD with pooled outcomes for LUTS. We identified 119 relevant articles in the literature and 18 articles fulfilled the inclusion criteria for the systematic review, of which, 5 articles had sufficient data for meta-analysis. Examining ADHD among individuals with LUTS, the odds ratio was 2.99 (95% CI 1.13, 7.88, p < 0.001), compared to controls. In multiple studies, the mean overall score for LUTS, using a standardized measure, was significantly higher in patients with ADHD in comparison to controls, and the severity of ADHD was positively associated with the severity of LUTS. Younger age in children was correlated with a higher LUTS score. Different subtypes of urinary incontinence demonstrated differences in behavioral problems and psychiatric comorbidity. Sex differences in LUTS were not consistent across articles. Our results indicate clinically significant associations between ADHD and LUTS in children. Because LUTS and ADHD are common disorders in children, clinicians should be aware of these associations as they inform optimal assessment and treatment strategies.

Parasacral transcutaneous electrical stimulation for overactive bladder in children: An assessment per session

Neuromodulation has emerged as an effective therapeutic option for treatment of OAB in children. However, to our knowledge, no study has yet evaluated the results of neuromodulation on a session-by-session basis. The aim of this study was to evaluate the rate of complete response of overactive bladder (OAB) symptoms for each session of transcutaneous electrical stimulation (TENS), in a protocol of 20 sessions of therapy. This is a prospective study of the improvement of LUTS in children with isolated OAB. Included in this study were children over the age of 4 years who complained of urinary urgency, had bell-or tower-shaped uroflowmetry patterns, and post-void residual <10% of expected capacity for their age and/or less than 20mL. No patient was treated with an anticholinergic. Children were excluded with lower urinary tract symptoms (LUTS) secondary to urinary tract abnormalities. All patients underwent parasacral transcutaneous neurostimulation (TENS). The development of symptoms was observed right before each session using a visual analog scale (VAS) in which 0 means the absence of improvement and 10 represents maximum improvement of symptoms. We noted a complete resolution of symptoms (urgency, urge incontinence, frequency, and holding maneuvers) in some patients starting after the third session. In the 10th and 20th (last) sessions, 12 (17.4%) and 38 (55.1%) patients reported a complete resolution of symptoms. After complete resolution, 12 (17.4%) patients reported that their symptoms worsened to a minimum level of 40% improvement, but this was temporary and all returned to 100% improvement. Children who showed an improvement level greater than 50% in the fifth treatment session were 4.18 (p=0.007) times more likely to have success in the last treatment session. We found that a patient can experience complete symptom resolution as quickly as following the third session of TENS. The complete response rate progressively increases with the number of sessions, slowly until the 12th session and more rapidly after that. When symptom improvement of at least 50% is reported in the fifth session, there is a higher chance that the patient will have full resolution of symptoms at the end of treatment.

Can urinary nerve growth factor and bladder wall thickness correlation in children have a potential role to predict the outcome of non-monosymptomatic nocturnal enuresis?

Measurement of bladder wall thickness (BWTh) by ultrasound has been introduced as a new and promising technique to assess bladder dysfunction, and increased levels of nerve growth factor have also been reported in the bladder tissue and urine of patients with sensory urgency and detrusor overactivity (DO). In this study we aimed to generate a clinically useful tool with urinary nerve growth factor levels and ultrasonographic BWTh to find possible pathogenetic clues and prognostic indicators as guides for the choice of therapy of non-monosymptomatic nocturnal enuresis. A total of 110 children, aged 6-16 years old, were involved in this prospective study. Group 1 consisted of children with non-monosymptomatic nocturnal enuresis (n = 40), Group 2 of children with monosymptomatic nocturnal enuresis (n = 40) and Group 3 of children with healthy normal controls (n = 30). Children were evaluated with detailed history and physical examination, including neurologic examination; they were asked to complete a self-reported questionnaire and a 3-day bladder diary with the aid of their parents. The number of wet nights, the number of voids per night, the presence of daytime voiding symptoms (urgency, urge incontinence, incontinence, holding maneuvers, frequency), fluid intake, and any history of urinary tract infections (UTIs) were recorded. Monosymptomatic nocturnal enuresis and non-monosymptomatic nocturnal enuresis diagnosis was made using the International Children's Continence Society definition. Urinary nerve growth factor levels were measured by enzyme-linked immunosorbent assay and BWTh was measured transabdominally by a uroradiologist who specialized in pediatric ultrasonography. Urinary nerve growth factor levels were normalized by urinary creatinine levels and compared in all subgroups. The mean age of the study group was 9.6 (range 6-16) years. The mean BWTh was significantly increased in Group 1 compared with Group 2 (4.33 ± 1.12 mm, 2.33 ± 1.03 mm; p < 0.001) and healthy controls (4.33 ± 1.12 mm, 1.86 ± 0.57 mm; p < 0.001, respectively). Urinary levels of nerve growth factor corrected to urine creatinine (NGF/Cr) significantly increased in Group 1 with to Group 2 (2.75 ± 1.15 vs. 0.58 ± 0.15; p < 0.001) and controls (2.75 ± 1.15 vs.0.28 ± 0.10; p < 0.001, respectively). In receiver operating characteristic analysis, BWTh was found to have sensitivity of 95% and specificity of 85.7% (3.00 area under the curve [AUC] 0.937; 95%) and NGF/Cr had sensitivity of 97.5% and specificity of 98.6% (0.885; AUC, 999; 95%) in predicting lower urinary tract symptoms (LUTS) for non-monosymptomatic nocturnal enuresis (NMNE) (Figure). In our study we have investigated that BWTh together with urinary NGF levels normalized to the concentration of urinary creatinine (NGF/Cr) may predict daytime voiding problems in children with primary nocturnal enuresis (PNE). The main basis of this study is previous findings which demonstrated that ultrasonography (US)-based measurement of BWTh is a useful diagnostic parameter for LUTS in children, and that increased levels of NGF in bladder tissue and urine such as sensory urgency, DO, and overactive bladder (OAB) was indicated by clinical and experimental studies. The present study demonstrated that urinary NGF/Cr levels and BWTh measurements were significantly increased in patients with NMNE with daytime urinary symptoms (urgency, urge-incontinence, incontinence, frequency) showing symptoms of an OAB than controls and MNE. BWTh measurements and NGF/Cr values, as non-invasive tools, may guide therapy and improve outcomes in the treatment of children with NMNE. Further studies including a larger number of patients would be of great interest.

The Impact of Gene Polymorphisms on the Success of Anticholinergic Treatment in Children with Overactive Bladder.

Aim. To determine the impact of gene polymorphisms on detrusor contraction-relaxation harmony in children with lower urinary tract symptoms (LUTS). Materials and Methods. Toilet trained children older than 5 years of age with LUTS and normal neurological examination underwent videourodynamic study. The control group was composed of age matched children with no voiding complaints. The study group who filled out the voiding dysfunction symptom score before and after the treatment received standard oxybutynin treatment and was reevaluated 1 year after treatment. Genomic DNA was isolated from all patients and subjected to PCR for amplification. Genotyping of ARGHEF10, ROCK2, ADRB3, and CYP3A4 was carried out with Polymerase Chain Reaction- Restriction Fragment Length Polymorphism (PCR-RFLP) method. Results. 34 (45%) and 42 (55%) patients were enrolled in the study and control group, respectively. ARGEF10 GG, ADRB3 TC, and CYP3A4 AG genotype patients displayed insignificant difference between pre- and posttreatment voiding dysfunction symptom score and bladder volumes. Conclusions. The polymorphism of genes in the cholinergic pathway did not significantly differ clinical parameters. On the other hand, polymorphic patients in the adrenergic pathway seemed to suffer from clinical disappointment. For this reason, we think that the neglected adrenergic pathway could be a new therapeutic target for the treatment of anticholinergic resistant LUTS in children.

The Iciq-Cluts: The First Screener Questionnaire for Lower Urinary Tract Symptoms in Children

Purpose To date no validated instruments are available to screen lower urinary tract symptoms (LUTS) in children, even if several questionnaires deal with clinical outcome. We developed and tested for validity a screener tool (ICIQ-CLUTS), to detect LUTS in children Material and Methods A 12-items questionnaire had been designed by experts, in a children's (ICIQ-CLUTSchildren) and parents' (ICIQ-CLUTSparents) version, and submitted to a standard cross-cultural adaptation process, simultaneously in English, Italian and German languages. Items investigated: age, gender, urinary tract infection, enuresis, daytime incontinence, daytime frequency, urgency, voiding postponement, straining to void, urge incontinence, feeling of incomplete emptying, bowel movements. Questionnaires have been administered, anonymously and blended, to children (age 10-18 years) and to parents of children aged 5-18 years presenting for LUTS (cases) or attending paediatric/urological clinics for reasons different that LUTS (controls); post-operative controls and uncontrolled insulin-dependent-diabetes being excluded.A Case-Report-Form comprehended history, urinalysis, bladder diary, flowmetry/PVR and a final clinician's judgment. Acceptability of ICIQ-CLUTS children and ICIQ-CLUTS parents were evaluated as percentage of missing items. ICIQ-CLUTS children and ICIQ-CLUTS parents scores were matched to clinician's judgement (taken as gold standard) in order to produce sensitivity and specificity (confidence interval 5-10%; level of confidence 95%). Results A total of 345 questionnaires were completed (267 by children and parents, 75 by parents and 3 by children). Final clinician's judgement identified 197 children as LUTS+ and the remaining 148 as LUTS-. Low percentage of missing items confirmed acceptability of ICIQ-CLUTS children (average missing items:1.7%) and ICIQ-CLUTSparents (average missing items:2.0).Sensitivity and specificity were, respectively,85% and 81% for ICIQ-CLUTS children and 87% and 70% for ICIQ-CLUTS parents. Conclusions Data analysis confirms ICIQ-CLUTS as valid and easy tool to screen LUTS in general paediatric population. ICIQ-CLUTS might be used to reconfigurate prevalence of LUTS in children, which was previously evaluated without validated instruments.