Mechanism to translation: Neural prostheses for the lower urinary tract

Parkinson's disease caused by the loss of dopaminergic neurons induces not only motor dysfunction but also lower urinary tract dysfunction. Patients with Parkinson's disease have recently been reported to experience both urge urinary incontinence (overactive bladder) and stress urinary incontinence, the latter of which occurs when the pressure of the bladder exceeds that of the urethra. Vibegron is a highly selective novel β3 -adrenoceptor agonist approved for the treatment of overactive bladder. However, how β3 -adrenoceptor agonists affect urethral function remains unclear. In a clinical report, the urethral function of patients with Parkinson's disease was shown to be degraded. The present study aimed to investigate the effects of vibegron on lower urinary tract activity in a rat model of Parkinson's disease. In a rat model of Parkinson's disease induced by unilateral 6-hydroxydopamine injection into the substantia nigra pars compacta, we examined the effects of vibegron on bladder and urethral activity. Cystometric analysis revealed that, compared with vehicle injection, intravenous injection of 3 mg/kg vibegron significantly increased the inter-contraction interval (p < .05) and reduced voiding pressure (p < .01). However, no significant effects on urethral function were observed. The results of the present study provide corroborating evidence that bladder dysfunction is suppressed by the administration of vibegron in Parkinson's disease model rats, confirming that vibegron is effective for treating overactive bladder without further worsening urethral function. These findings may contribute to a better understanding of the mechanisms of β3 -adrenoceptor agonists.

Neuromodulation is a therapeutic technique that is well-established in the treatment of idiopathic Lower urinary tract (LUT) dysfunction such as overactive bladder (OAB). We have recently developed a novel neuromodulation approach, Transcutaneous Electrical Spinal Cord Neuromodulation (TESCoN) and demonstrated its acute effects on LUT dysfunction after spinal cord injury (SCI) during urodynamic studies. We found that TESCoN can promote urinary storage and induce urinary voiding when delivered during urodynamic studies. The objective of this study was to determine whether TESCoN can retrain the spinal neural networks to induce chronic improvement in the LUT, such that positive changes can persist even in the absence of stimulation. In addition, we wished to examine the effect of TESCoN on LUT dysfunction due to multiple pathologies. To achieve this objective, 14 patients [SCI = 5, stroke = 5, multiple sclerosis (MS) = 3, and idiopathic OAB (iOAB) = 1] completed 24 sessions of TESCoN over the course of 8 weeks. Patients completed urodynamic studies before and after undergoing TESCoN therapy. Additionally, each subject completed a voiding diary and the Neurogenic Bladder Symptom Score questionnaire before and after receiving TESCoN therapy. We found that TESCoN led to decreased detrusor overactivity, improved continence, and enhanced LUT sensation across the different pathologies underlying LUT dysfunction. This study serves as a pilot in preparation for a rigorous randomized placebo-controlled trial designed to demonstrate the effect of TESCoN on LUT function in neurogenic and non-neurogenic conditions.New And NoteworthyNon-Surgical modality to reduce incidence of urinary incontinence and improve neurogenic bladder symptom scores (NBSS) in individuals with neurogenic bladder due to spinal cord injury or stroke.

Background Lower urinary tract (LUT) dysfunction is very common in Parkinson's disease (PD) patients. However, the number of studies conducted on LUT dysfunction and its related factors in Chinese PD patients is very limited, and there is no international consensus concerning the results. Methods This cross-sectional study enrolled 100 Chinese PD patients. The patients were classified based on their overactive bladder symptom score (OABSS) and then assigned to either a PD with overactive bladder (PD-OAB) group or a PD with no overactive bladder (PD-NOAB) group. A binary logistic regression analysis was performed to identify the accompanying factors for overactive bladder (OAB). Next, correlations between the OABSS and patient sex, age, age of onset, disease duration, MDS-UPDRS-III, H-Y stage, PD subtype, treatment, education, and nonmotor symptoms were analyzed to identify factors correlated with LUT dysfunction. Results Eighty nine (89%) of the PD patients suffered from LUT dysfunction, and OAB was diagnosed in 45 (45%) of those PD patients. The most common lower urinary tract (LUT) symptom in the PD patients was nighttime frequency (86%), followed by urgency (50%), urge incontinence (34%), and daytime frequency (17%). Patients in the PD-OAB group had an older age and age of onset, were at a more advanced Hoehn–Yahr stage, and had more severe motor symptoms and nonmotor symptoms, including worse cognition, and a greater incidence of REM sleep behavior disorder (RBD). A binary logistic regression analysis showed that a lower Frontal Assessment Battery (FAB) score, higher H-Y stage, and RBD accompanied with a higher prevalence of OAB in PD patients. A multiple linear regression analysis showed that the OABSS was significantly influenced by the FAB score, H-Y stage, RBD, and age. Conclusions The FAB score, H-Y stage, and RBD are accompanying factors for OAB. A higher OABSS in PD patients was related to a lower FAB score for frontal lobe executive dysfunction, a higher H-Y stage for severity of motor disorders, RBD, and an older age.

The goal of this review is to elucidate the role of urodynamics in the assessment and management of lower urinary tract (LUT) dysfunction in children. Many children with LUT dysfunction will improve with an explanation of bladder and bowel function, advice on fluid intake and bathroom schedules, and treatment of constipation. Among those who fail to respond, urodynamics may be useful in guidance. There are four types of urodynamic studies: non-invasive urodynamics, uroflow, invasive urodynamics, and videourodynamics. This review outlines the information that can be obtained from these studies. Biofeedback is a non-invasive urodynamic technique which involves the visualization of LUT function to teach the child control over these muscles particularly the pelvic floor muscle. In the absence of success, other options are available for LUT management. Patterns of non-invasive urodynamics can be helpful in diagnosing and planning care for children with LUT dysfunction particularly if the pattern is consistent with history and home bladder diaries. Many diagnoses respond to pelvic floor exercises taught by biofeedback. Constipation plays a large role in LUT dysfunction and may respond to diet, medication, and biofeedback. More invasive testing and treatment is available for the few who do not respond.

IS SPINA BIFIDA OCCULTA ASSOCIATED WITH LOWER URINARY TRACT DYSFUNCTION IN CHILDREN?

Chapter 21 - Lower urinary tract dysfunction in patients with multiple sclerosis

The aim of this review is to outline the clinical presentation, pathophysiology and evaluation of lower urinary tract (LUT) dysfunction in Parkinson's disease and other parkinsonian syndromes including multiple system atrophy, dementia with Lewy bodies, progressive supranuclear palsy and corticobasal degeneration. LUT dysfunction commonly occurs in neurological disorders, including patients with parkinsonian syndromes. The pattern of LUT dysfunction and its severity are variable, depending upon the site of lesion within the neural pathways. Parkinsonian syndromes are broadly divided into Parkinson's disease (PD) and a typical parkinsonian syndromes such as multiple system atrophy (MSA), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Different parkinsonian syndromes have distinct clinical features (e.g. dysautonomia, early dementia, supranuclear gaze palsy, higher cortical signs), and the pattern of LUT dysfunction and its severity can differ. LUT dysfunction is a common feature in patients with parkinsonian syndromes. Recognising the pattern of LUT dysfunction during the assessment of these patients can help management and possibly facilitate an earlier diagnosis.

The lower urinary tract has the main function of urine storage and voiding. The integrity of the lower urinary tract nerve supply is necessary for its proper function. Neurological disorders can lead to lower urinary tract dysfunction (LUTD) and cause lower urinary tract symptoms (LUTS). Common causes of neurogenic LUTS or LUTD include spinal cord injury, multiple sclerosis, Parkinson's disease, cerebrovascular accidents, cauda equina syndrome, diabetes mellitus, and multiple system atrophy. The pathophysiology is categorized according to the nature of the onset of neurological disease. Assessment requires clinical evaluation, laboratory tests, imaging, and urodynamic studies. Impaired voiding is most often managed by clean intermittent self-catheterization if the postvoid residual urine exceeds 100 ml, whereas storage symptoms are most often managed by antimuscarinic medications. Intradetrusor injection of botulinum toxin type A is emerging as an effective treatment for managing refractory neurogenic detrusor overactivity. This review provides an overview of the clinical characteristics, diagnosis, and management of LUTD in patients with central and peripheral common neurological diseases.

Complex organization of CNS and PNS pathways is necessary for the coordinated and reciprocal functions of the urinary bladder, urethra and urethral sphincters. Injury, inflammation, psychogenic stress or diseases that affect these nerve pathways and target organs can produce lower urinary tract (LUT) dysfunction. Numerous neuropeptide/receptor systems are expressed in the neural pathways of the LUT and non-neural components of the LUT (e.g., urothelium) also express peptides. One such neuropeptide receptor system, pituitary adenylate cyclase-activating polypeptide (PACAP; Adcyap1) and its cognate receptor, PAC1 (Adcyap1r1), have tissue-specific distributions in the LUT. Mice with a genetic deletion of PACAP exhibit bladder dysfunction and altered somatic sensation. PACAP and associated receptors are expressed in the LUT and exhibit neuroplastic changes with neural injury, inflammation, and diseases of the LUT as well as psychogenic stress. Blockade of the PACAP/PAC1 receptor system reduces voiding frequency in preclinical animal models and transgenic mouse models that mirror some clinical symptoms of bladder dysfunction. A change in the balance of the expression and resulting function of the PACAP/receptor system in CNS and PNS bladder reflex pathways may underlie LUT dysfunction including symptoms of urinary urgency, increased voiding frequency, and visceral pain. The PACAP/receptor system in micturition pathways may represent a potential target for therapeutic intervention to reduce LUT dysfunction.

Are lower urinary tract symptoms in children associated with urinary symptoms in their mothers?

The Role of Urinary Microbiota in Lower Urinary Tract Dysfunction: A Systematic Review

Outcomes of vesicoureteral reflux in children with non-neurogenic lower urinary tract dysfunction treated with dextranomer/hyaluronic acid copolymer (Deflux)

Chapter 12 - Lower urinary tract dysfunction in patients with peripheral nervous system lesions

The impact of the original International Children’s Continence Society (ICCS) terminology document on lower urinary tract (LUT) function resulted in the global establishment of uniformity and clarity in the characterization of LUT function and dysfunction in children across multiple healthcare disciplines. The present document serves as a stand-alone terminology update reflecting refinement and current advancement of knowledge on paediatric LUT function. A variety of worldwide experts from multiple disciplines within the ICCS leadership who care for children with LUT dysfunction were assembled as part of the standardization committee. A critical review of the previous ICCS terminology document and the current literature was performed. Additionally, contributions and feedback from the multidisciplinary ICCS membership were solicited. Following a review of the literature over the last 7 years, the ICCS experts assembled a new terminology document reflecting current understanding of bladder function and LUT dysfunction in children using the resources from the literature review, expert opinion and ICCS member feedback. The present ICCS terminology document provides a current and consensus update to the evolving terminology and understanding of LUT function in children.

The impact of the original International Children's Continence Society (ICCS) terminology document on lower urinary tract (LUT) function resulted in the global establishment of uniformity and clarity in the characterization of LUT function and dysfunction in children across multiple healthcare disciplines. The present document serves as a stand-alone terminology update reflecting refinement and current advancement of knowledge on pediatric LUT function. A variety of worldwide experts from multiple disciplines within the ICCS leadership who care for children with LUT dysfunction were assembled as part of the standardization committee. A critical review of the previous ICCS terminology document and the current literature was performed. Additionally, contributions and feedback from the multidisciplinary ICCS membership were solicited. Following a review of the literature over the last 7 years, the ICCS experts assembled a new terminology document reflecting current understanding of bladder function and LUT dysfunction in children using the resources from the literature review, expert opinion and ICCS member feedback. The present ICCS terminology document provides a current and consensus update to the evolving terminology and understanding of LUT function in children. Neurourol. Urodynam. 35:471-481, 2016. © 2015 Wiley Periodicals, Inc.