Brain Activity Among Children With Overactive Bladder and Daytime Urinary Incontinence and Healthy Children

The aim of this study is to investigate whether the activity in brain areas controlling the bladder is different among children suffering from Overactive Bladder (OAB) and Daytime Urinary Incontinence (DUI) compared to age- and gender-matched healthy children without bladder symptoms. Moreover, the aim is to investigate if sacral transcutaneous electric nerve stimulation (TENS) has a central mechanism of action. Children with OAB and DUI will be recruited from involved pediatric departments, and functional magnetic resonance imaging (fMRI) will be performed before and after 10 weeks of sacral TENS. In healthy children without bladder symptoms, only the baseline fMRI will be performed.

Daytime Urinary Incontinence (DUI) is a common condition among children affecting 2.1-21.8 % of children aged 4.5-17 years. DUI is most often caused by a functional overactive bladder (OAB) leading to urgent desire to void (urgency) and frequent urinations (frequency). In some children with functional OAB and DUI, the bladder detrusor is overactive when performing a urodynamic investigation, but this is not evident for all children suffering from OAB and DUI. The etiology of OAB and DUI is not yet fully established and might be multifactorial. A few studies among adults have shown that adult women with OAB and DUI has more activity in brain areas controlling the bladder compared to adult women without bladder symptoms. Moreover, one study among adult women has shown a decrease in brain activity in areas controlling the bladder after sacral TENS treatment. This has led to a hypothesis that increased activity in the brain is a pathophysiological mechanism of OAB and DUI. Brain activity among children with OAB and DUI has not yet been investigated. Therefore, the objectives of this study is: 1. To investigate the activity in brain areas controlling the bladder among children with OAB and DUI and age- and gender-matched children without bladder symptoms AND 2. To investigate if sacral TENS has a centrally modulatory effect on the brain activity in areas controlling the bladder among children with OAB and DUI. Methods: The study consists of two sub-studies. The first sub-study is a cross-sectional study, whereas the second sub-study is an interventional cohort study. Forty-five children with OAB and DUI and 20 healthy children without bladder symptoms will be recruited. The study includes one structural MRI as well as two sessions of functional MRIs (only one functional MRI for healthy participants), one session prior to and after 10 weeks of sacral TENS treatment. The functional MRI session consist of a functional MRI with full bladder followed by a functional MRI with empty bladder. Moreover, the study participants and/or their parents are asked to fill in frequency and volume charts, Dry Pie, screening tools to rule out attention deficit hyperactivity disorder and autism spectrum disorders, and quality of life-questionnaires (WHO-5 and PinQ).

Inclusion Criteria: * Overactive Bladder as per International Children's Continence Society criteria (cases only). * At least 2 incontinence episodes per week (cases only). * No urinary tract symptoms (healthy participants only). * More than 3 daily urinations. * Normal clinical examination. Exclusion Criteria: * Known urogenital abnormality affecting the lower urinary tract function. * Prior surgery in the urinary tract (except circumcision). * Known neurological diseases or prior cerebral surgery. * Known neuropsychiatric disorders or suspicion of those by screening. * Treatment with pharmacological agents affecting the brain function. * Prior treatment with Enuresis Alarm or Transcutaneous Electrical Nerve Stimulation. * Prior or current treatment with mirabegron or oxybutynin. * Current urinary tract infection. * Current constipation according to Rome IV-criteria or faecal incontinence. * Claustrophobia. * Metallic items in the body contraindicating MRI-scans. * Abnormal uroflowmetry (healthy participants only).