Functional mapping of the lower urinary tract by epidural electrical stimulation of the spinal cord in decerebrated cat model.

Several neurologic diseases including spinal cord injury, Parkinson's disease or multiple sclerosis are accompanied by disturbances of the lower urinary tract functions. Clinical data indicates that chronic spinal cord stimulation can improve not only motor function but also ability to store urine and control micturition. Decoding the spinal mechanisms that regulate the functioning of detrusor (Detr) and external urethral sphincter (EUS) muscles is essential for effective neuromodulation therapy in patients with disturbances of micturition. In the present work we performed a mapping of Detr and EUS activity by applying epidural electrical stimulation (EES) at different levels of the spinal cord in decerebrated cat model. The study was performed in 5 adult male cats, evoked potentials were generated by EES aiming to recruit various spinal pathways responsible for LUT and hindlimbs control. Recruitment of Detr occurred mainly with stimulation of the lower thoracic and upper lumbar spinal cord (T13-L1 spinal segments). Responses in the EUS, in general, occurred with stimulation of all the studied sites of the spinal cord, however, a pronounced specificity was noted for the lower lumbar/upper sacral sections (L7-S1 spinal segments). These features were confirmed by comparing the normalized values of the slope angles used to approximate the recruitment curve data by the linear regression method. Thus, these findings are in accordance with our previous data obtained in rats and could be used for development of novel site-specific neuromodulation therapeutic approaches.

Clasificación, diagnóstico y tratamiento de los trastornos miccionales en la infancia / Classification, diagnosis and treatment of urinary disorders in childhood

La disfunción vesical o disfunción del tracto urinario inferior(DTUI), traducción literal del inglés de Lower urinary Tract Disfunction (LUTD) puede ser causa del 40% de las consultas en pediatría. Estos trastornos suponen una alteración en cualquiera de las fases del ciclo miccional y pueden responder a causas neurológicas, anatómicas o funcionales. Es muy importante realizar una adecuada historia clínica que nos permita conocer al paciente de manera global de manera que podamos lograr un correcto diagnóstico de la causa de la disfunción y así poder realizar un tratamiento dirigido. La evaluación de la mayoría de los niños con disfunción vesical puede limitarse a una anamnesis exhaustiva, un examen físico y pruebas no invasivas, como un análisis de orina y un urocultivo. En niños seleccionados, una evaluación más extensa incluye estudios de imagen urológicos, mediciones del flujo urinario y determinación del residuo postmiccional. En cuanto a las herramientas terapéuticas, partiremos de pautas higiénico-dietéticas básicas y de aplicación global a las que podremos asociar terapia conductual, farmacológica, fisioterápica o quirúrgica, siempre de manera individualizada.(AU)

Vesical disfunction or Lower urinary Tract Dysfunction (LUTD), can be the cause of 40% of pediatric consultations. Dysfunctions of the lower urinary tract involve an alteration in any of the phases of the voiding cycle and may respond to neurological, anatomical or functional causes. It is very important to take an adequate clinical history that allows us to know the patient globally so that we can achieve a correct diagnosis of the cause of the lower urinary tract dysfunction and thus be able to carry out targeted treatments. The evaluation for most children with bladder dysfunction can be limited to a thorough history, physical examination, and noninvasive testing, such as a urinalysis and urine culture. In selected children, more extensive evaluation includes urologic imaging studies, measurements of urinary flow, and post-void residual determination. As for therapeutic tools, we will start from basic hygienic-dietary guidelines of global application to which we can associate behavioral, pharmacological, physiotherapy or surgical therapy, always in an individualized manner.(AU)

Hematuria persistente en Pediatría: ¿cuándo hacer algo más que observar? / Persistent hematuria in Pediatrics: When to do more than observe?

El objetivo principal del estudio diagnóstico de la hematuria persistente es descartar la presencia de patología renal potencialmente grave. La asociación de proteinuria requiere llevar a cabo controles periódicos de función renal, tensión arterial y cuantificación de proteinuria ante la sospecha de glomerulopatía subyacente. La biopsia renal, ante la persistencia de hematuria y proteinuria, nos dará en la mayoría de ocasiones el diagnóstico definitivo. Presentamos el caso de una niña con hematuria controlada en consulta de nefrología infantil durante años sin deterioro del filtrado glomerular en la que se decide realizar biopsia renal, que nos da el diagnóstico definitivo. La nefropatía IgA es la enfermedad glomerular primaria más frecuente en el mundo y requiere seguimiento durante toda la vida por el posible deterioro de la función renal a largo plazo. En la actualidad no existen protocolos específicos de tratamiento para niños, y los más empleados siguen las guías KDIGO 2021, dirigidas a adultos.(AU)

The main goal of the diagnostic study of persistent hematuria is to rule out the presence of potentially serious renal pathology. The association with proteinuria requires periodic monitoring of renal function, blood pressure, and quantification of proteinuria in cases of suspected underlying glomerulopathy. The kidney biopsy, in the presence of persistent hematuria and proteinuria, will often provide a definitive diagnosis. We present a girl with hematuria monitored in pediatric nephrology department for years without deterioration of glomerular filtration in whom it was decided to perform a kidney biopsy, which gave us the definitive diagnosis. IgA nephropathy is the most common primary glomerular disease worldwide and requires lifelong monitoring due to possible long-term deterioration of kidney function. Currently, there are no specific treatment protocols for children, and the most commonly used ones follow the KDIGO 2021 guidelines, which are directed at adults.(AU)

Síndrome hemolítico urémico atípico secundario a infección neumocócica invasiva / Atypical hemolytic uremic syndrome secondary to invasive pneumococcal infection

Introducción: El síndrome hemolítico urémico (SHU) es una patología infrecuente y grave en pediatría. Se clasifica en SHU “típico” o “atípico” en función de su etiopatogenia. Se caracteriza por la triada: anemia hemolítica microangiopática, trombopenia e insuficiencia renal, siendo característica la presencia de esquistocitos en sangre periférica. Caso clínico: Varón de 13 meses sin antecedentes personales ni familiares de interés. Consulta por fiebre alta de 5 días, sintomatología catarral, astenia, ictericia, vómitos, diarrea y oliguria. Exploración física: mal estado general, HTA estadio I, coloración pálido-ictérica, taquicardia, polipnea, hipoventilación basal pulmonar derecha y edemas pretibiales. Pruebas complementarias: analítica sanguínea: Hb 8,4 g/dl, 20.000/mm3 plaquetas, leucocitosis con desviación izquierda, urea 186 mg/dl, creatinina 3,27 mg/dl [FGe(Schwartz_2009): 10,5 ml/min/1,73 m2], PCR, PCT y LDH elevadas, haptoglobina baja. Sistemático/sedimento urinario: proteinuria 0,95 mg/mg, hematuria glomerular. Frotis sangre periférica: 5% Esquistocitos. Test de Coombs directo: positivo. Radiografía torácica: condensación basal pulmonar derecha. Ante presencia de la triada: anemia hemolítica microangiopática, trombopenia e insuficiencia renal es diagnosticado de SHU en contexto de neumonía, iniciando tratamiento de soporte en UCIP, furosemida y antibioterapia empírica. Actividad ADAMTS13 y determinación de Shiga-toxina: negativas. Hemocultivo: + Streptococcus pneumoniae. Estudio de complemento normal. Empeoramiento funcional renal, precisando hemodialfiltración veno-venosa continua y administración de eculizumab. Presentó mejoría progresiva y alta con diagnóstico final de SHU secundario a sepsis neumocócica. Seguimiento en consulta de Nefrología Pediátrica, actualmente padece enfermedad renal crónica en estadio G3A2. Conclusiones: Es importante realizar un diagnóstico y tratamiento precoces para mejorar su pronóstico vital y funcional renal, estableciendo protocolos de manejo inicial y seguimiento multidisciplinar.(AU)

Introduction. Hemolytic uremic syndrome (HUS) is a rare and serious pathology in pediatrics. It is classified as “typical” or “atypical” HUS depending on its etiopathogenesis. It is characterized by the triad: microangiopathic hemolytic anemia, thrombopenia and renal failure, with the presence of schistocytes in peripheral blood being characteristic. Case report: 13-month-old male with no personal or family history of interest. Consultation due to high fever for 5 days, catarrhal symptoms, asthenia, jaundice, vomiting, diarrhea and oliguria. Physical examination: Poor general condition, Stage-I arterial hypertension, pale-jaundiced muco-cutaneous, tachycardia, polypnea, hypoventilation at the right lung base and pretibial edema. Complementary tests: Blood analysis: Hb 8.4 g/dl, platelets 20,000/mm3, leukocytosis with left deviation, urea 186mg/dl, creatinine 3.27 mg/dl [eGFR(Schwartz_2009): 10.5 ml/min/1.73 m2], elevated CRP, PCT and LDH, low haptoglobin. Systemic/urinary sediment: proteinuria 0.95 mg/mg, glomerular hematuria. Peripheral blood smear: 5% Schistocytes. Direct Coombs test: positive. Chest x-ray: right pulmonary basal condensation. In the presence of the triad: microangiopathic hemolytic anemia, thrombopenia and renal failure, HUS was diagnosed in the context of pneumonia, initiating supportive treatment in the PICU, furosemide and empirical antibiotic therapy. ADAMTS13 activity and Shiga-toxin determination: negative. Blood culture: + Streptococcus pneumoniae. Worsening renal function, requiring continuous veno-venous hemodiafiltration and administration of eculizumab. He showed progressive improvement and was discharged with diagnosis of HUS secondary to pneumococcal sepsis. Follow-up in Pediatric Nephrology consultation, currently suffering from chronic kidney disease (stage G3A2). Conclusions: It is important to carry out early diagnosis and treatment to improve vital and renal functional prognosis, establishing initial management protocols and multidisciplinary follow-up.(AU)

Mothers' perception of prenatal counseling following diagnosis of congenital anomalies of the urinary tract.

Congenital abnormalities of the genitourinary tract are the most common sonographically identified malformations. Although prenatal diagnosis seldom modifies perinatal management, it can cause significant anxiety in parents. We aimed to assess how parents perceived the prenatal counseling they had received in our institution. Using a questionnaire, we evaluated by phone the mothers of 78 children diagnosed prenatally with urological tract anomalies between January 2018 and May 2019. Overall, mothers were satisfied and reassured by the prenatal counseling they received, although 19% of the mothers found the time from diagnosis to specialist consultation to be too long. Forty percent of the responders stated that the most important information they needed to hear during the specialist consultation was management and not diagnosis. Specialist counseling should focus on explaining postnatal management, should be offered as soon as possible, and should include practical aspects, especially concerning outpatient care.

Quantitative evaluation of upper urinary tract pump function in pigs with acute unilateral lower ureteral obstruction by 640-slice dynamic volume CT.

BACKGROUND: It is a challenging problem to differentiate obstructive hydronephrosis from noninvasive evaluation of renal pelvis and ureteral motility in patients. The purpose of this study was to explore the value of 640-slice dynamic volume CT (DVCT) in the quantitative measurement of upper urinary tract (UUT) pump function after acute unilateral lower ureteral obstruction in pigs. METHODS: In this study, a perfusion pig model was constructed by constant pressure perfusion testing of the renal pelvis and left nephrostomy. The perfusion and pressure measuring devices were connected to create a state of no obstruction and acute obstruction of the lower part of the left ureter. After successful modelling, continuous dynamic volume scanning of the bilateral renal excretion phase was performed with 640-slice DVCT, and pump functions of the renal pelvis and part of the upper ureter were calculated and analysed. No obstruction or acute obstruction of the lower part of the left ureter was observed. Pump functions of the renal pelvis and part of the upper ureter were determined. RESULTS: The results showed that after LUUT fistulostomy, the time difference between the average UUT volume and positive volume value increased gradually, and the calculated flow velocity decreased, which was significantly different from that of the RUUT. The volume difference of the LUUT increased significantly in mild obstruction. In the bilateral control, the volume change rate of the LUUT increased with mild obstruction and decreased with severe obstruction, and there was a significant difference between the left and right sides. CONCLUSION: The continuous dynamic volume scan and measurement of 640-slice DVCT can obtain five pump function datasets of UUT in pigs with acute lower ureteral obstruction.

Characteristics and risk factors of lower urinary tract dysfunction in patients with Parkinson's disease: A systematic evaluation and meta-analysis.

To systematically evaluate the risk factors of lower urinary tract dysfunction in patients with Parkinson's disease(PD), and to provide theoretical basis for clinical medical staff to identify the risk factors of lower urinary tract dysfunction in patients with PD. From the establishment of the database to January 2021, PubMed, the Cochrane Library, EMBASE, Web of Science, other English database, were searched for literatures about the risk factors of lower urinary tract dysfunction in patients with Parkinson's disease. According to the inclusion and exclusion criteria, after browsing the title, abstract and full text, the high-quality literature in line with the inclusion criteria was selected, and the Newcastle-Ottawa Scale（NOS）document quality evaluation tool was used to evaluate the literature quality and extract the data. The included research results were analyzed by RevMan 5.3 software. A total of 8 studies were included for Meta analysis. The results showed that 7 of the 20 related risk factors were statistically significant, and the statistically significant risk factors were duration of disease [Mean Difference (MD)= 0.59, 95% Confidence Interval (CI) (0.04, 1.14), P < 0.005], age [MD = 2.01, 95%CI (-0.36, 3.34), P < 0.005], Hoehn-Yahr (H-Y) score >2 [Odds Ratio (OR) = 1.56, 95%CI (1.09, 2.23), P < 0.001], sleep disorder [OR = 1.79, 95%CI (1.36,2.35), P < 0.001], constipation [OR = 1.88, 95%CI (1.42,2.48), P < 0.001], unified Parkinson's disease rating scale (UPDRS III) [MD= 4.43, 95%CI (2.20, 6.66), P < 0.001], Mini-mental state examination (MMSE) [MD = -1.16, 95%CI (1.23, -1.09), P < 0.001]. Age, duration of disease, H-Y score >2, sleep disorder, constipation, higher UPDRS Ⅲ score and lower MMSE score were the risk factors of lower urinary tract dysfunction in patients with Parkinson's disease.

Improves symptoms and urinary biomarkers in refractory interstitial cystitis/bladder pain syndrome patients randomized to extracorporeal shock wave therapy versus placebo.

Extracorporeal shock wave therapy (ESWT) has been shown to improve symptoms in patients with interstitial cystitis/bladder pain syndrome (IC/BPS); however, there is a lack of objective evidence. We measured change of urinary biomarker levels in 25 patients with IC/BPS received ESWT or placebo once a week for 4 weeks. Urines were collected from participants at baseline, 4 and 12 weeks post treatment. A representative 41 inflammatory growth factors, cytokines, and chemokines in urine were measured using a MILLIPLEX immunoassay kit. Symptom bother was assessed by O'Leary-Sant symptom scores (OSS), and visual analog scale (VAS) for pain. The ESWT group exhibited a significant reduction in the OSS and VAS compared to the placebo group 4 weeks post-treatment (P < 0.05), and the effects were persistent at 12 weeks. The difference in urinary markers change in ESWT versus placebo was P = 0.054 for IL4, P = 0.013 for VEGF, and P = 0.039 for IL9 at 4 weeks. The change of urine biomarker was not significant in other biomarkers or all the measured proteins at 12 weeks. The current data suggest that IL4, IL9, and VEGF mediation may be involved in its pathophysiologic mechanisms and response to LESW treatment.

Utility of pre-transplant lower urinary tract investigation in pediatric renal transplant population after referral: A 16-year institutional experience.

To evaluate the clinical utility of pre-renal transplant LUT investigations in pediatric populations after their referral for transplant evaluation based on the etiology of their ESRD. A 16 year retrospective review of patients undergoing RT performed at our institution was performed. Patients were stratified into two groups: Group 1-non-urologic and Group 2-urologic etiology for ESRD. Baseline characteristics, pre-transplant LUT investigations, and urologic interventions were assessed. One-year clinical outcomes were compared between those with and without LUT investigations following referral for renal transplantation (RT). 227 patients and 97 patients were identified for Groups 1 and 2, respectively. 19% of Group 1 and 73% of Group 2 had VCUG, while 1% and 13%, respectively, had UDS ordered following referral for RT. In both groups, >50% of VCUG and UDS were ordered without specific clinical concerns. These had low likelihood of prompting interventions, both pre-transplant (Group 1-VCUG 0%, UDS 0%; Group 2-VCUG 0%, UDS 8%) or post-transplant (Group 1-0%, Group 2-5%). In both groups, LUT investigation following referral for RT did not lead to differences in 1 year outcomes assessed. In anticipation of pediatric RT, LUT investigations ordered without clinical indications did not provide information that altered management prior to transplantation.

Severe urinary tract damage secondary to primary bladder neck obstruction in women.

OBJECTIVE: To present the clinical and radiological characteristics of women with severe structural deterioration of the bladder and upper urinary tract secondary to Primary Bladder Neck Obstruction (PBNO), and their outcomes after bladder neck incision (BNI). METHODS: Retrospective evaluation of adult women who underwent BNI for PBNO at one institution. Patients were assessed for symptoms, renal function, structural abnormalities of the urinary tract and video-urodynamics. PBNO diagnosis was confirmed with video-urodynamics in all patients. BNI was performed at the 4-5 and/or 7-8 o'clock positions. Postoperative symptoms, PVR, uroflowmetry and renal function were evaluated and compared to baseline. RESULTS: Median patient age was 56.5 years (range 40-80). All presented with urinary retention-four were on clean intermittent Catheterization (CIC) and two with a Foley catheter. All patients had bladder wall thickening and diverticula. Four women had elevated creatinine levels, bilateral hydronephrosis was present in five (83.3%). After BNI, all patients resumed spontaneous voiding without the need for CIC. Median Qmax significantly improved from 2.0 [1.0-4.0] mL/s to 15 [10-22.7] mL/s (p = 0.031). Median PVR decreased from 150 to 46 [22-76] mL (p = 0.031). There were no postoperative complications. Creatinine levels returned to normal in 3/4 (75%) patients. CONCLUSION: PBNO in women may result in severe damage to the bladder and upper urinary tract. Despite severe structural abnormalities of the bladder, BNI was effective in reducing symptoms and improving structural and functional abnormalities of the lower and upper urinary tract.

Regional Cerebral Cortical Atrophy is Related to Urinary Tract Symptoms in Parkinson's Disease.

BACKGROUND AND PURPOSE: Lower urinary tract symptoms (LUTS) are the most common nonmotor symptoms usually occurring mid-stage of Parkinson's disease (PD); however, its underlying mechanisms are unknown. We aimed to assess whether corticometry or volumetry can identify a pattern of cerebral cortical changes in PD patients with LUTS. METHODS: We recruited 85 idiopathic PD patients and performed corticometry and volumetry on various cortical regions using each patient's magnetic resonance imaging. To identify a correlation between the cortical thickness/volume and nonmotor symptoms scale domain 7 scores, which represent the severity of LUTS, we performed general linear model and region of interest analyses. RESULTS: Significant regional thinning of the left precuneus, left temporal pole, left precentral, right precuneus, and right pars opercularis was correlated with nonmotor symptoms scale domain 7 scores. We also found that cortical volumes of left precuneus and left frontal pole were inversely correlated with the severity of urinary symptoms. CONCLUSIONS: This study showed that the thicknesses and volumes of several cortical regions were significantly correlated with the severity of LUTS in PD patients. The findings of regional atrophy and thinning of specific cortical regions in this study provide additional evidence that multiple cortical regions, especially the precuneus cortex, not only may be involved in urinary dysfunctions of PD patients but also may help to elucidate the exact underlying mechanisms for LUTS in PD patients.

Timing urinary tract reconstruction in rats to avoid hydronephrosis and fibrosis in the transplanted fetal metanephros as assessed using imaging.

Chronic kidney disease leads to high morbidity rates among humans. Kidney transplantation is often necessary for severe symptoms; however, options for new curative treatments are desired because of donor shortage. For example, it has been established that the kidneys can efficiently generate urine after transplantation of the metanephros, ureter, and bladder as a group. After transplantation, the urine can indirectly flow into the recipient's bladder using a stepwise peristaltic ureter system method where the anastomosis is created via the recipient's ureter for urinary tract reconstruction. However, the growth of the regenerated metanephros varies significantly, whereas the time window for successful completion of the stepwise peristaltic ureter system that does not cause hydronephrosis of the metanephros with bladder (ureter) is quite narrow. Therefore, this study was conducted to periodically and noninvasively evaluate the growth of the transplanted metanephros, ureter, and bladder in rats through computed tomography and ultrasonography. The ultrasonographic findings highly correlated to the computed tomography findings and clearly showed the metanephros and bladder. We found that the degree of growth of the metanephros and the bladder after transplantation differed in each case. Most of the rats were ready for urinary tract reconstruction within 21 days after transplantation. Optimizing the urinary tract reconstruction using ultrasonography allowed for interventions to reduce long-term tubular dilation of the metanephros due to inhibited overdilation of the fetal bladder, thereby decreasing the fibrosis caused possibly by transforming growth factor-ß1. These results may be significantly related to the long-term maturation of the fetal metanephros and can provide new insights into the physiology of transplant regeneration of the metanephros in higher animals. Thus, this study contributes to the evidence base for the possibility of kidney regeneration in human clinical trials.

The effect of ß3-adrenoceptor gene polymorphisms on lower urinary tract function in males.

PURPOSE: To clarify the role of Trp64Arg polymorphisms of the gene encoding the ß3-adrenoceptor for lower urinary tract function in males, the present study investigated the association between the Trp64Arg polymorphisms and lower urinary tract symptoms (LUTS) and function. METHODS: This prospective observational study included patients who underwent robot-assisted radical prostatectomy. Before surgery, blood samples were collected, and analyses of ß3-adrenoceptor gene polymorphism were performed using the real-time polymerase chain reaction. The present cohort was divided into patients with wild type (Trp64Trp) and with variant type (Trp64Arg + Arg64Arg), and LUTS and lower urinary tract function before surgery were compared between them. RESULTS: Wild type was found in 247 patients, with variant type in 129. There were no significant differences in LUTS between the two groups. Residual urine volume (PVR) (wild type: variant type = 47 ± 53 mL: 58 ± 77 mL, P = 0.04) and voiding time on uroflowmetry (wild type: variant type = 29 ± 15 s: 33 ± 17 s, P = 0.04) were significantly increased in the variant type. CONCLUSION: The Trp64Arg variant of the ß3-adrenoceptor gene significantly increased PVR and voiding time in men. However, it was not significantly associated with the emergence of LUTS. Thus, since the effect of ß3-adrenoceptor gene polymorphisms on the genitourinary organs might be weak, whether men possess the Trp64Arg variant of the ß3-adrenoceptor gene might not critically affect urinary quality of life, but modestly affect the lower urinary tract function.

Characterization of Lower Urinary Tract Dysfunction after Thoracic Spinal Cord Injury in Yucatan Minipigs.

There is an increasing need to develop approaches that will not only improve the clinical management of neurogenic lower urinary tract dysfunction (NLUTD) after spinal cord injury (SCI), but also advance therapeutic interventions aimed at recovering bladder function. Although pre-clinical research frequently employs rodent SCI models, large animals such as the pig may play an important translational role in facilitating the development of devices or treatments. Therefore, the objective of this study was to develop a urodynamics protocol to characterize NLUTD in a porcine model of SCI. An iterative process to develop the protocol to perform urodynamics in female Yucatan minipigs began with a group of spinally intact, anesthetized pigs. Subsequently, urodynamic studies were performed in a group of awake, lightly restrained pigs, before and after a contusion-compression SCI at the T2 or T9-T11 spinal cord level. Bladder tissue was obtained for histological analysis at the end of the study. All anesthetized pigs had bladders that were acontractile, which resulted in overflow incontinence once capacity was reached. Uninjured, conscious pigs demonstrated appropriate relaxation and contraction of the external urethral sphincter during the voiding phase. SCI pigs demonstrated neurogenic detrusor overactivity and a significantly elevated post-void residual volume. Relative to the control, SCI bladders were heavier and thicker. The developed urodynamics protocol allows for repetitive evaluation of lower urinary tract function in pigs at different time points post-SCI. This technique manifests the potential for using the pig as an intermediary, large animal model for translational studies in NLUTD.

Lower urinary tract and bowel dysfunction in spinocerebellar ataxias.

BACKGROUND: Little information is available in spinocerebellar ataxias (SCAs) regarding pelvic organ symptoms. The aim of this study was to characterize the lower urinary tract (LUT) and bowel dysfunction in autosomal dominant spinocerebellar ataxias. METHODS: Patients with confirmed SCAs attending a tertiary care service were approached about LUT and bowel complaints, and completed validated questionnaires: urinary symptom profile (USP), Qualiveen-Short form, International Prostate Symptom Score, and Neurogenic Bowel Dysfunction Score. SCA3 and SCA7 patients with urological complaints additionally underwent urodynamic studies (UDS). Patients' characterization included demographic, clinical (Scale for the Assessment and Rating of Ataxia (SARA), Inventory of Non-Ataxia Signs (INAS)), and genetic variables. Descriptive and comparative analyses were performed. RESULTS: Fifty-one patients participated: SCA1 (n = 4), SCA2 (n = 11), SCA3 (n = 13), SCA6 (n = 17), and SCA7 (n = 6). The prevalence of self-reported LUT symptoms was 60.8% (n = 31), whereas LUT symptoms was reported in 86.3%(n = 44) using the USP. Both storage and voiding symptoms were reported, urinary frequency and urgency being the most frequent (n = 34, 68%). Although LUT symptoms were most often classed as mild (n = 27, 61.4%), they impacted QoL in 38 patients (77.6%). Of these, 21 (55.3%) were not on pharmacological treatment for urinary dysfunction. Most common abnormalities in UDS (n = 14) were detrusor overactivity (storage phase) and detrusor underactivity (voiding phase). Bowel symptoms were less common (31.4%, n = 16) and of mild severity. CONCLUSION: LUT symptoms are prevalent in SCA patients and impact QoL, whereas bowel symptoms tend to be mild. These symptoms are overlooked by patients and physicians due to the complexity of neurological involvement in SCA, and therefore a multidisciplinary management approach should be adopted.

Sacral Neuromodulation for Lower Urinary Tract and Bowel Dysfunction in Animal Models: A Systematic Review With Focus on Stimulation Parameter Selection.

OBJECTIVE: Conventional sacral neuromodulation (SNM) has shown to be an effective treatment for lower urinary tract and bowel dysfunction, but improvements of clinical outcome are still feasible. Currently, in preclinical research, new stimulation parameters are being investigated to achieve better and longer effects. This systematic review summarizes the status of SNM stimulation parameters and its effect on urinary tract and bowel dysfunction in preclinical research. MATERIALS AND METHODS: The literature search was conducted using three databases: Ovid (Medline, Embase) and PubMed. Articles were included if they reported on stimulation parameters in animal studies for lower urinary tract or bowel dysfunction as a primary outcome. Methodological quality assessment was performed using the SYRCLE Risk of Bias (RoB) tool for animal studies. RESULTS: Twenty-two articles were eligible for this systematic review and various aspects of stimulation parameters were included: frequency, intensity, pulse width, stimulation signal, timing of stimulation, and unilateral vs. bilateral stimulation. In general, all experimental studies reported an acute effect of SNM on urinary tract or bowel dysfunction, whereas at the same time, various stimulation settings were used. CONCLUSIONS: The results of this systematic review indicate that SNM has a positive therapeutic effect on lower urinary tract and bowel dysfunction. Using low-frequency-SNM, high-frequency-SNM, bilateral SNM, and higher pulse widths showed beneficial effects on storage and evacuation dysfunction in animal studies. An increased variability of stimulation parameters may serve as a basis for future improvement of the effect of SNM in patients suffering from urinary tract or bowel dysfunction.

Stimulation Parameters for Sacral Neuromodulation on Lower Urinary Tract and Bowel Dysfunction-Related Clinical Outcome: A Systematic Review.

OBJECTIVE: Sacral neuromodulation (SNM) has been used to treat patients with lower urinary tract dysfunction and bowel dysfunction for many years. Success rates vary between 50% and 80%, indicating that there is much room for improvement. Altering stimulation parameters may result in improved outcome. This paper reports a systematic review of the clinical efficacy of nonconventional stimulation parameters on urinary tract and bowel dysfunction. MATERIALS AND METHODS: Three databases were used for the literature search: Ovid (Medline, Embase) and PubMed. Papers were screened by two independent reviewers, who also extracted data from these papers. Clinical papers studying SNM stimulation parameters, that is, intermittent stimulation, frequency, pulse width, and amplitude, in urinary tract and bowel dysfunction were included. Quality of included papers was assessed using standardized guidelines. RESULTS: Out of 5659 screened papers, 17 papers, studying various stimulation parameters, were included. Overall quality of these papers differed greatly, as some showed no risk of bias, whereas others showed high risk of bias. Stimulation parameters included intermittent stimulation, frequency, pulse width, amplitude, and unilateral vs. bilateral stimulation. Especially high frequency SNM and either a narrow or wide pulse width seem to improve efficacy in patients with bowel dysfunction. Additionally, implementation of short cycling intervals is promising to improve quality of life for patients with urinary tract or bowel dysfunction. CONCLUSION: The results of our systematic review indicate that stimulation parameters may improve efficacy of SNM in treatment of both urinary tract dysfunction and bowel dysfunction.

Interstitial cystitis/bladder pain syndrome and recurrent urinary tract infection and the potential role of the urinary microbiome.

Interstitial cystitis/bladder pain syndrome and recurrent urinary tract infections carry significant burden for those affected. As women enter the menopause, other factors may influence how these conditions manifest. The urinary microbiome has shown that the urine contains extensive numbers of bacteria. There is some evidence to suggest that it is altered depending on the menopausal state of the individual. It is possible that this alteration may go on to influence how the disease course of interstitial cystitis/bladder pain syndrome and recurrent urinary tract infections runs in the post-menopausal group. The review will explore these two conditions and the potential role of the urinary microbiome.

Improvement of lower urinary tract function by a selective serotonin 5-HT1A receptor agonist, NLX-112, after chronic spinal cord injury.

Spinal cord injury (SCI) above the lumbosacral level results in lower urinary tract dysfunction, including (1) detrusor hyperreflexia, wherein bladder compliance is low, and (2) a lack of external urethral sphincter (EUS) control, leading to detrusor-sphincter dyssynergia (DSD) with poor voiding efficiency. Experimental studies in animals have shown a dense innervation of serotonergic (5-HT) fibers and multiple 5-HT receptors in the spinal reflex circuits that control voiding function. Here, we investigated the efficacy of NLX-112 (a.k.a. befiradol or F13640), in regulating lower urinary tract function after T8 contusive SCI in rats. NLX-112 is a very potent, highly-selective, and fully efficacious 5-HT1A receptor agonist, which has been developed for the treatment of L-DOPA-induced dyskinesia in Parkinson's disease patients. We performed urodynamics tests and external urethral sphincter electromyogram recordings to assess lower urinary tract function while NLX-112 was infused through the femoral vein in rats with chronic complete SCI or contusive SCI. The dose response studies indicated that NLX-112 was able to improve voiding behavior by regulating both detrusor and EUS activity. These included improvements in voiding efficiency, reduction of detrusor hyperactivity, and phasic activity of EUS during the micturition period. In addition, the application of a selective 5-HT1A receptor antagonist, WAY100635, reversed the improved detrusor and EUS activity elicited by NLX-112. In summary, the current data suggest that pharmacological activation of 5-HT1A receptors by NLX-112 may constitute a novel therapeutic strategy to treat neurogenic bladder after SCI.

Voiding time as a predictor for urinary tract function and health status.

AIM: In this study, we investigated self-measured voiding time in the Japanese population. METHODS: A survey questionnaire was used to determine self-measured voiding time in Japanese participants aged ≥20 years. In addition to demographic data such as age and sex, relevant medical conditions, including hypertension, diabetes mellitus, renal impairment and other disorders, were also recorded. Voiding time was measured whenever the participant had the urge to void. RESULTS: In total, 2493 healthy individuals (1347 men, mean ± SD, age 60.50 ± 12.16 years, and 1146 women, 51.16 ± 12.97 years) participated in the survey. Self-measured voiding time was 27.71 ± 20.25 s for men, and 17.49 ± 11.87 s for women. Additionally, 1227 participants with certain diseases were included (1026 men, aged 67.12 ± 9.93 years, and 201 women, 60.26 ± 11.02 years). In this group, self-measured voiding time was significantly longer at P < 0.01 (30.71 ± 20.98 s in men, 21.28 ± 15.56 s in women). In men whose international prostate symptom score (IPSS) was >7, voiding time was significantly longer (healthy men: IPSS ≤7 n = 868, 23.9 ± 14.88 s, IPSS ≥8 n = 479, 34.6 ± 26.05 s, P < 0.05, men with comorbidities: IPSS ≤7: n = 504, 25.64 ± 15.63 s, IPSS ≥8: n = 522, 35.6 ± 24.11 s, P < 0.05). CONCLUSIONS: This self-reported internet survey revealed that self-measured voiding time was longer in men than women regardless of age, and was significantly prolonged with age regardless of sex. Furthermore, self-measured voiding time could be a good screening tool to predict urinary function and health status. Geriatr Gerontol Int ••; ••: ••-•• Geriatr Gerontol Int 2020; ••: ••-••.