bTUNED: transcutaneous tibial nerve stimulation for neurogenic lower urinary tract dysfunction.

OBJECTIVE: To present the protocol for a randomized controlled trial (RCT) evaluating the efficacy and safety of transcutaneous tibial nerve stimulation (TTNS) for refractory neurogenic lower urinary tract dysfunction (NLUTD). STUDY DESIGN AND RESULTS: bTUNED (bladder and TranscUtaneous tibial Nerve stimulation for nEurogenic lower urinary tract Dysfunction) is an international multicentre, sham-controlled, double-blind RCT investigating the efficacy and safety of TTNS. The primary outcome is success of TTNS, defined as improvements in key bladder diary variables at study end compared to baseline values. The focus of the treatment is defined by the Self-Assessment Goal Achievement (SAGA) questionnaire. Secondary outcomes are the effect of TTNS on urodynamic, neurophysiological, and bowel function outcome measures, as well as the safety of TTNS. CONCLUSIONS: A total of 240 patients with refractory NLUTD will be included and randomized 1:1 into the verum or sham TTNS group from March 2020 until August 2026. TTNS will be performed twice a week for 30 min during 6 weeks. The patients will attend baseline assessments, 12 treatment visits and follow-up assessments at the study end.

Neuro-Urology and Biobanking: An Integrated Approach for Advancing Research and Improving Patient Care.

Understanding the molecular mechanisms underlying neuro-urological disorders is crucial for the development of targeted therapeutic interventions. Through the establishment of comprehensive biobanks, researchers can collect and store various biological specimens, including urine, blood, tissue, and DNA samples, to study these mechanisms. In the context of neuro-urology, biobanking facilitates the identification of genetic variations, epigenetic modifications, and gene expression patterns associated with neurogenic lower urinary tract dysfunction. These conditions often present as symptoms of neurological diseases such as Alzheimer's disease, multiple sclerosis, Parkinson's disease, spinal cord injury, and many others. Biobanking of tissue specimens from such patients is essential to understand why these diseases cause the respective symptoms and what can be done to alleviate them. The utilization of high-throughput technologies, such as next-generation sequencing and gene expression profiling, enables researchers to explore the molecular landscape of these conditions in an unprecedented manner. The development of specific and reliable biomarkers resulting from these efforts may help in early detection, accurate diagnosis, and effective monitoring of neuro-urological conditions, leading to improved patient care and management. Furthermore, these biomarkers could potentially facilitate the monitoring of novel therapies currently under investigation in neuro-urological clinical trials. This comprehensive review explores the synergistic integration of neuro-urology and biobanking, with particular emphasis on the translation of biobanking approaches in molecular research in neuro-urology. We discuss the advantages of biobanking in neuro-urological studies, the types of specimens collected and their applications in translational research. Furthermore, we highlight the importance of standardization and quality assurance when collecting samples and discuss challenges that may compromise sample quality and impose limitations on their subsequent utilization. Finally, we give recommendations for sampling in multicenter studies, examine sustainability issues associated with biobanking, and provide future directions for this dynamic field.

[Sacral neuromodulation for bladder voiding dysfunction: Experience at a French university center]. / Neuromodulation sacrée pour trouble de la vidange vésicale : expérience d'un centre universitaire français.

OBJECTIVE: To report the experience of a university hospital center with sacral neuromodulation for patients with bladder voiding disorders. MATERIAL AND METHODS: All patients who underwent sacral neuromodulation between 1998 and 2022 for bladder voiding disorders were included. Medical records were analyzed retrospectively, and population, efficacy and follow-up data were collected. RESULTS: A total of 134 patients underwent test implantation and 122 patients were analyzed. 68 patients (56%) were implanted with a definitive neuromodulation device. Mean age was 43±16 years and BMI 25.5±5.4kg/m2. 74% were women. Bladder voiding disorder was due to sphincter hypertonia in 51% of cases, with associated bladder hypocontractility in 29%. The spontaneous micturition rate after implantation increased from 34% to 92%. Implantation results appeared to be better in patients with sphincter hypertonia, whether or not associated with bladder hypocontractility. The benefit was most often present with a frequency of 5Hz (54.4%). Side-effects were present in 52% of cases at 5 years, and in 85% of cases were pain in relation to the implanted devices. They resolved under medical treatment or after revision of the device (27% of cases at 5 years). CONCLUSION: SNM is effective in micturition recovery, but has side effects. Urodynamic mechanism and etiology may provide clues for modulating NMS box settings and determining predictive factors for NMS success. Data from other centers are needed to identify reliable predictive factors.

Functional MRI in neuro-urology: A narrative review.

Neuro-imaging has given urologists a new tool to investigate the neural control of the lower urinary tract. Using functional magnetic resonance imaging (fMRI), it is now possible to understand which areas of the brain contribute to the proper function of the storage and voiding of the lower urinary tract. This field of research has evolved from simple anatomical descriptions to elucidating the complex micturition network. A keyword search of the Medline database was conducted by two reviewers for relevant studies from January 1, 2010, to August 2022. Of 2047 peer-reviewed articles, 49 are included in this review. In the last decade, a detailed understanding of the brain-bladder network has been described, elucidating a dedicated network, as well as activated areas in the brainstem, cerebellum, and cortex that share reproducible connectivity patterns. Research has shown that various urological diseases can lead to specific changes in this network and that therapies used by urologists to treat lower urinary tract symptoms (LUTS) are also able to modify neuronal activity. This represents a set of potential new therapeutic targets for the management of the lower urinary tract symptoms (LUTS). fMRI technology has made it possible to identify subgroups of responders to various treatments (biofeedback, anticholinergic, neuromodulation) and predict favourable outcomes. Lastly, this breakthrough understanding of neural control over bladder function has led to treatments that directly target brain regions of interest to improve LUTS. One such example is the use of non-invasive transcranial neuromodulation to improve voiding symptoms in individuals with multiple sclerosis.

Corticotropin-Releasing Hormone from the Pontine Micturition Center Plays an Inhibitory Role in Micturition.

Lower urinary tract or voiding disorders are prevalent across all ages and affect >40% of adults over 40 years old, leading to decreased quality of life and high health care costs. The pontine micturition center (PMC; i.e., Barrington's nucleus) contains a large population of neurons that localize the stress-related neuropeptide, corticotropin-releasing hormone (CRH) and project to neurons in the spinal cord to regulate micturition. How the PMC and CRH-expressing neurons in the PMC control volitional micturition is of critical importance for human voiding disorders. To investigate the specific role of CRH in the PMC, neurons in the PMC-expressing CRH were optogenetically activated during in vivo cystometry in unanesthetized mice of either sex. Optogenetic activation of CRH-PMC neurons led to increased intermicturition interval and voided volume, similar to the altered voiding phenotype produced by social stress. Female mice showed a significantly more pronounced phenotype change compared with male mice. These effects were eliminated by CRH-receptor 1 antagonist pretreatment. Optogenetic inhibition of CRH-PMC neurons led to an altered voiding phenotype characterized by more frequent voids and smaller voided volumes. Last, in a cyclophosphamide cystitis model of bladder overactivity, optogenetic activation of CRH-PMC neurons returned the voiding pattern to normal. Collectively, our findings demonstrate that CRH from PMC spinal-projecting neurons has an inhibitory function on micturition and is a potential therapeutic target for human disease states, such as voiding postponement, urinary retention, and underactive or overactive bladder.SIGNIFICANCE STATEMENT The pontine micturition center (PMC), which is a major regulator of volitional micturition, is neurochemically heterogeneous, and excitatory neurotransmission derived from PMC neurons is thought to mediate the micturition reflex. In the present study, using optogenetic manipulation of CRH-containing neurons in double-transgenic mice, we demonstrate that CRH, which is prominent in PMC-spinal projections, has an inhibitory function on volitional micturition. Moreover, engaging this inhibitory function of CRH can ameliorate bladder hyperexcitability induced by cyclophosphamide in a model of cystitis. The data underscore CRH as a novel target for the treatment of voiding dysfunctions, which are highly prevalent disease processes in children and adults.

Lower urinary tract electrical sensory assessment: a systematic review and meta-analysis.

OBJECTIVES: To summarize the current literature on lower urinary tract electrical sensory assessment (LUTESA), with regard to current perception thresholds (CPTs) and sensory evoked potentials (SEPs), and to discuss the applied methods in terms of technical aspects, confounding factors, and potential for lower urinary tract (LUT) diagnostics. METHODS: The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Medline (PubMed), Embase and Scopus were searched on 13 October 2020. Meta-analyses were performed and methodological qualities of the included studies were defined by assessing risk of bias (RoB) as well as confounding. RESULTS: After screening 9925 articles, 80 studies (five randomized controlled trials [RCTs] and 75 non-RCTs) were included, comprising a total of 3732 patients and 692 healthy subjects (HS). Of these studies, 61 investigated CPTs exclusively and 19 reported on SEPs, with or without corresponding CPTs. The recording of LUTCPTs and SEPs was shown to represent a safe and reliable assessment of LUT afferent nerve function in HS and patients. LUTESA demonstrated significant differences in LUT sensitivity between HS and neurological patients, as well as after interventions such as pelvic surgery or drug treatments. Pooled analyses showed that several stimulation variables (e.g. stimulation frequency, location) as well as patient characteristics might affect the main outcome measures of LUTESA (CPTs, SEP latencies, peak-to-peak amplitudes, responder rate). RoB and confounding was high in most studies. CONCLUSIONS: Preliminary data show that CPT and SEP recordings are valuable tools to more objectively assess LUT afferent nerve function. LUTESA complements already established diagnostics such as urodynamics, allowing a more comprehensive patient evaluation. The high RoB and confounding rate was related to inconsistency and inaccuracy in reporting rather than the technique itself. LUTESA standardization and well-designed RCTs are crucial to implement LUTESA as a clinical assessment tool.

Prioritization of risk situations in neuro-urology: guidelines from Association Française d'Urologie (AFU), Association Francophone Internationale des Groupes d'Animation de la Paraplégie (A.F.I.G.A.P.), Groupe de Neuro-urologie de Langue Française (GENULF), Société Française de Médecine Physique et de Réadaptation (SOFMER) and Société Interdisciplinaire Francophone d'UroDynamique et de Pelvi-Périnéologie (SIFUD-PP).

PURPOSE: The current health crisis has drastically impacted patient management in many fields, including neuro-urology, leading to a mandatory reorganization. The aim of this work was to establish guidelines regarding the prioritization and optimal timing of each step of neurogenic lower urinary tract dysfunction management. METHODS: A steering committee included urologists and physical medicine and rehabilitation practitioners. Based on a literature review and their own expertise, they established a comprehensive risk-situation list and built a risk scale, allowing multiple other experts to score each clinical situation. New recommendations were generated using a Delphi process approach. RESULTS: Forty-nine experts participated in the rating group. Among the 206 initial items, 163 were selected and divided into four domains, diagnosis and assessment, treatment, follow-up, and complications, and two sub-domains, general (applicable for all neurological conditions) and condition-specific [varying according to the neurological condition (spinal cord injury, multiple sclerosis, brain injury, Parkinsonism, dysraphism, lower motor neuron lesions)]. The resulted guidelines are expert opinions established by a panel of French-speaking specialists, which could limit the scalability of this work. CONCLUSIONS: The present multidisciplinary collaborative work generates recommendations which complement existing guidelines and help clinicians to reorganize their patients' list in the long term with a personalized medicine approach, in the context of health crisis or not.

Functional urology: Practice patterns and training aspirations among urologists in Brazil.

PURPOSE: Urology has rapidly evolved during the last decades, incorporating new technologies faster than most specialties. The challenge to maintain a competent workforce that is prepared to deliver proper contemporary treatment has become increasingly difficult and newly graduated urologists throughout the world typically lack the skills to practice many urological subspecialties. We performed a survey to evaluate the practice patterns and educational aspirations in functional urology (FU) among Brazilian urologists. METHODS: A web-based survey was sent to board-certified Brazilian urologists to collect data on clinical practice and training aspirations in four subareas of FU: female urology, urodynamics, postprostatectomy incontinence (PPI), and neurourology. We evaluated urologists' clinical and surgical workload in each subarea and investigated educational training aspirations to identify areas and training formats of interest. RESULTS: A total of 366 urologists (mean age 47.7 + 10.7 years) completed the survey. Mean time since completion of residency was 17.9 + 11.9 years. Of the respondents, 176 (53%) perform urodynamics, 285 (83.1%) SUI surgeries, 159 (47.6%) PPI surgeries, 194 (58.1%) third line OAB procedures, 168 (48.9%) pelvic organ prolapse (POP), and 88 (26.3%) bladder augmentation. Mid-urethral sling is the most performed SUI surgery and transobturator is the preferred route (64.0%). For those performing POP surgery, 40.5% use mesh in at least 50% of their cases, and the vaginal route is used in most cases (75.4%) for apical prolapse. For PPI, 64.6% use artificial sphincter in most surgeries and only 8.1% perform at least 5 surgeries/year. Being fellowship-trained and working in an academic hospital are associated with a higher chance of being active in FU. Most urologists are interested in receiving training in PPI, female SUI, and POP and a hands-on course is the preferred educational method (81%). CONCLUSIONS: Most urologists in Brazil are involved in the evaluation and treatment of FU patients, but few have a large volume of patient visits and surgical procedures. Completing a fellowship program and working in an academic practice are associated with a higher chance of being a FU practitioner. There is a high interest in training for PPI, female SUI, and POP.

[Prioritization of risk situations in neuro-urology: Guidelines based on the Delphi method from Association française d'urologie (AFU), Association francophone internationale des groupes d'animation de la paraplégie (AFIGAP), Groupe de neuro-urologie de langue française (GENULF), Société française de médecine physique et de réadaptation (SOFMER) and Société interdisciplinaire francophone d'urodynamique et de pelvi-périnéologie (SIFUD-PP)]. / Priorisation des situations à risque en neuro-urologie : recommandations par méthode Delphi de l'Association française d'urologie (AFU), l'Association francophone internationale des groupes d'animation de la paraplégie (AFIGAP), le Groupe de neuro-urologie de langue française (GENULF), la Société française de médecine physique et de réadaptation (SOFMER) et la Société interdisciplinaire francophone d'urodynamique et de pelvi-périnéologie (SIFUD-PP).

PURPOSE: During the COVID-19 pandemic, a care reorganization was mandatory, and affected patients in different areas, including management of neurogenic lower urinary tract dysfunction. This work aims to provide validated schedule concerning the assessment and management of patients in neuro-urology. METHODS: Based on a literature review and their own expertise, a steering committee composed of urologists and physical medicine and rehabilitation practitioners generated a comprehensive risk-situation list and built a risk scale. A panel of French-speaking experts in neuro-urology was asked to define the timing for each clinical situation and validated these new recommendations through a Delphi process approach. RESULTS: The 49 experts included in the rating group validated 163 propositions among the 206 initial items. The propositions were divided into four domains - diagnosis and assessment, treatment, follow-up, and complications - and two sub-domains - general (applicable for all neurological conditions) and condition-specific (varying according to the neurological condition (spinal cord injury, multiple sclerosis, brain injury, Parkinsonism, spinal dysraphism, lower motor neuron lesions)). CONCLUSIONS: This multidisciplinary collaborative work generates recommendations based on expert opinion, providing a validated timing for assessment and management of patients in neuro-urology which may help clinicians to reorganize their patients' list with a personalized medicine approach, in a context of health crisis or not.

[An initial lack of knowledge of the perineal anatomy does not influence the learning of intermittent self-catheterization in women]. / La méconnaissance initiale de l'anatomie périnéale n'influence pas l'apprentissage de l'auto-sondage intermittent chez la femme.

AIM: To evaluate the impact of female perineal anatomy knowledge on the success of a first learning of intermittent self-catheterization (ISC). METHODS: Thirty subjects benefited from educational diagnosis, training and follow-up during 2 visits in a neuro-urology department. Three knowledge anatomical tests were carried out: a freehand drawing, then a diagram to be annotated and a self-location of the following 6 structures (labia majora, labia minora, clitoris, urethral meatus, vaginal orifice, anus) as well as a physiological knowledge test. A correction was made after annotating the diagram to perfect the learning process before performing the procedure. RESULTS: Of the women studied, 83.3% had a neurological pathology and 77.7% had a gyneco-obstetrical history. Half of them had undergone perineal rehabilitation. Our study shows a lack of knowledge of the perineum prior to learning self-catheterization: 43.3% thought they knew it partially and 46.7% reported that they did not know it. Fifty-three percent of the subjects did not indicate the urethral meatus and 43.3% did not annotate the vaginal orifice on the diagram. Difficulties in anatomical transposition were observed: the urethral meatus was self-located in only 43.3% of subjects and 30% did not locate the vaginal orifice. Previous perineal rehabilitation was not benefical in the self-recognition of anatomical structures. However, all the patients, including those who did not initially locate the urethral meatus, acquired the technique of ISC. CONCLUSION: Intial perineal anatomy ignorance in women was frequent but was not an obstacle to learning ISC. LEVEL OF PROOF: 4.

Efficiency and satisfaction with telephone consultation of follow-up patients in neuro-urology: Experience of the COVID-19 pandemic.

AIM: The COVID-19 pandemic led to limit patients' visits to the neuro-urology department. Telemedicine was seen as a pragmatic solution to provide follow-up care. This study aimed to assess the efficiency and satisfaction of a telephone consultation in neuro-urology. METHODS: During the pandemic, the scheduled medical visits were converted into telephone consultation. For each teleconsultation, the physician assessed the efficiency and the patient-rated global satisfaction of the teleconsultation. The physician and the patient assessed whether this teleconsultation replaced a physical visit. RESULTS: About 358 neurologic patients were included in the study. The mean efficiency of the telephone consultation was 9.3/10 (±1.5). The mean global satisfaction was 9.0/10 (±1.3). The majority of the patients (52.4%) would prefer a physical consultation. 90.2% might convert some clinic visits to teleconsultations in the future. No agreement was found between the patient and the physician when they were asked if the teleconsultation replaced the physical consultation initially scheduled (weight kappa = 0.02; 95% confidence interval = [-0.06 to 0.11]). Cognitive impairment, difficulty to obtain relevant information, and lack of physical examination were unfavorable to the efficiency of the teleconsultation. Cognitive impairment, embarrassing nature of the teleconsultation, and preference for a physical consultation were unfavorable to satisfaction of the patient. CONCLUSION: Telemedicine in neuro-urology was associated with a high satisfaction of the patients and was described as efficient by the physicians. Despite this, the majority of the patients reported a preference for physical consultation. The COVID-19 pandemic might be an opportunity to refine our practices in neuro-urology and to develop telemedicine.

Anti-Nogo-A Antibodies As a Potential Causal Therapy for Lower Urinary Tract Dysfunction after Spinal Cord Injury.

Loss of bladder control is common after spinal cord injury (SCI) and no causal therapies are available. Here we investigated whether function-blocking antibodies against the nerve-fiber growth inhibitory protein Nogo-A applied to rats with severe SCI could prevent development of neurogenic lower urinary tract dysfunction. Bladder function of rats with SCI was repeatedly assessed by urodynamic examination in fully awake animals. Four weeks after SCI, detrusor sphincter dyssynergia had developed in all untreated or control antibody-infused animals. In contrast, 2 weeks of intrathecal anti-Nogo-A antibody treatment led to significantly reduced aberrant maximum detrusor pressure during voiding and a reduction of the abnormal EMG high-frequency activity in the external urethral sphincter. Anatomically, we found higher densities of fibers originating from the pontine micturition center in the lumbosacral gray matter in the anti-Nogo-A antibody-treated animals, as well as a reduced number of inhibitory interneurons in lamina X. These results suggest that anti-Nogo-A therapy could also have positive effects on bladder function clinically.SIGNIFICANCE STATEMENT After spinal cord injury, loss of bladder control is common. Detrusor sphincter dyssynergia is a potentially life-threatening consequence. Currently, only symptomatic treatment options are available. First causal treatment options are urgently needed in humans. In this work, we show that function-blocking antibodies against the nerve-fiber growth inhibitory protein Nogo-A applied to rats with severe spinal cord injury could prevent development of neurogenic lower urinary tract dysfunction, in particular detrusor sphincter dyssynergia. Anti-Nogo-A therapy has entered phase II clinical trial in humans and might therefore soon be the first causal treatment option for neurogenic lower urinary tract dysfunction.

Detrusor overactivity is missed by stopping urodynamic investigation at a bladder volume of 500 mL.

OBJECTIVES: To investigate whether detrusor overactivity (DO) is missed in a relevant percentage of patients if the urodynamic investigation (UDI) is stopped at a filling volume of 500 mL due to the fear of bladder overdistention, in patients with lower urinary tract symptoms and high bladder capacity. PATIENTS AND METHODS: A consecutive series of 1598 patients with a bladder capacity of >500 mL in the bladder diary undergoing UDI due to lower urinary tract dysfunction (LUTD) was prospectively investigated. UDI was performed according to Good Urodynamic Practices recommended by the International Continence Society. UDI was stopped at strong desire to void or in case of autonomic dysreflexia, vesico-uretero-renal reflux, bladder pain or discomfort. RESULTS: Of the 1598 patients (594 women, 1004 men), 1282 (80%) and 316 (20%) had neurogenic and non-neurogenic LUTD, respectively. Overall, DO was detected in 66% (1048/1598), in 71% (910/1282) with neurogenic and in 44% (138/316) with non-neurogenic LUTD. DO occurred in 16% (263/1598, 95% confidence interval [CI] 14.7-18.4%) only at a bladder volume >500 mL. This phenomenon was significantly (P < 0.001) more frequent in patients with neurogenic (18% [236/1282], 95% CI 16.4-20.6%) compared with non-neurogenic (9% [27/316], 95% CI 5.9-12.1%) LUTD. CONCLUSIONS: In both neurological and non-neurological patients with high bladder capacity, we strongly recommend not to stop UDI at a bladder volume of 500 mL, as DO might be missed in a relevant percentage leading to inappropriate patient treatment.

Desmopressin for treating nocturia in patients with multiple sclerosis: A systematic review: A report from the Neuro-Urology Promotion Committee of the International Continence Society (ICS).

AIMS: To systematically assess all available evidence on efficacy and safety of desmopressin for treating nocturia in patients with multiple sclerosis (MS). METHODS: This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies were identified by electronic search of Cochrane register, Embase, Medline, Scopus (last search March 3, 2018) and by screening of reference lists and reviews. RESULTS: After screening of 7015 abstracts, 8 prospective, and 1 retrospective studies were included enrolling a total of 178 patients. The mean patient age ranged between 43 and 51 years. A significant decrease in the number of micturitions per night was reported in 5 studies. An increase in the maximum hours of uninterrupted sleep was only found in two studies. A significant reduction of the volume of nocturnal incontinence was described in one study. The patient satisfaction rates ranged from 56% to 82%. The rate of adverse events was between 0% and 57.9%. The rate of hyponatremia ranged from 0% to 23.5% and other commonly reported adverse events were headache, nausea, fluid retention, rhinitis/epistaxis, malaise, and swollen ankles. Risk of bias and confounding was relevant in all studies. CONCLUSIONS: Preliminary data suggest that desmopressin might be effective for treating nocturia in patients with MS. However, adverse events are relatively common, the overall quality of evidence is low and the number of studied patients is very limited. Further studies with newer formulations of desmopressin are highly warranted.

Alpha-blockers for treating neurogenic lower urinary tract dysfunction in patients with multiple sclerosis: A systematic review and meta-analysis. A report from the Neuro-Urology Promotion Committee of the International Continence Society (ICS).

AIM: We aimed to systematically assess the evidence on the efficacy and safety of alpha-blockers in patients with multiple sclerosis (MS) suffering from neurogenic lower urinary tract dysfunction (NLUTD). METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was used to perform this systematic review. An electronic search of Cochrane register, Embase, Medline, Scopus (last search 3 March 2018) and screening of reference lists as well as reviews were used to identify the studies. Articles were included if they reported on efficacy/safety of alpha-blockers for the treatment of NLUTD in patients with MS. RESULTS: After screening of 7'015 abstracts, three studies enrolling a total of 50 patients were included: one randomized, placebo-controlled, single-blind trial and two prospective cohort studies. Alpha-blocker treatment was successful in 50% to 96% of the patients. Pooling data from the three included studies, the relative risk for successful alpha-blocker treatment was 3.89 (95% confidence interval 2.7-7.0). The general safety profile of alpha-blockers was favorable with 8% of the patients reporting adverse events. CONCLUSIONS: Alpha-blockers may be effective and safe for treating NLUTD in female and male patients with MS but the studies were small and the overall quality of evidence was low. To make definitive conclusions, well designed randomized controlled trials are highly warranted.

High EDSS can predict risk for upper urinary tract damage in patients with multiple sclerosis.

BACKGROUND: Neurogenic lower urinary tract dysfunction (NLUTD) is very common in patients with multiple sclerosis (MS), and it might jeopardize renal function and thereby increase mortality. Although there are well-known urodynamic risk factors for upper urinary tract damage, no clinical prediction parameters are available. OBJECTIVE: We aimed to assess clinical parameters potentially predicting urodynamic risk factors for upper urinary tract damage. METHODS: A consecutive series of 141 patients with MS referred from neurologists for primary neuro-urological work-up including urodynamics were prospectively evaluated. Clinical parameters taken into account were age, sex, duration, and clinical course of MS and Expanded Disability Status Scale (EDSS). RESULTS: Multivariate modeling revealed EDSS as a clinical parameter significantly associated with urodynamic risk factors for upper urinary tract damage (odds ratio = 1.34, 95% confidence interval (CI) = 1.06-1.71, p = 0.02). Using receiver operator characteristic (ROC) curves, an EDSS of 5.0 as cutoff showed a sensitivity of 86%-87% and a specificity of 52% for at least one urodynamic risk factor for upper urinary tract damage. CONCLUSION: High EDSS is significantly associated with urodynamic risk factors for upper urinary tract damage and allows a risk-dependent stratification in daily neurological clinical practice to identify MS patients requiring further neuro-urological assessment and treatment.

Early urological care of patients with spinal cord injury.

PURPOSE: After spinal cord injury (SCI), the initial goals of urological management include maintaining safe storage of urine with efficient bladder emptying, maximising urinary continence, and minimising the risk of urological complications. METHODS: This review was performed according to the methodology recommended by the Joint SIU-ICUD International Consultation. Embase and Medline databases were used to identify literature relevant to the early urological care of SCI patients. Recommendations were developed by consensus and graded using a modified Oxford system which identifies level of evidence (LOE) and grade of recommendation (GOR). RESULTS: Clinicians must ensure appropriate bladder emptying immediately after SCI (LOE 3, GOR A) and perform the initial neuro-urological assessment within 3 months after injury (LOE 3, GOR A), including history, validated questionnaires, bladder diary, physical examination, measurement of renal function, and urinary tract imaging (LOE 4, GOR B). Urodynamics, if available video-urodynamics, must be performed to detect and specify lower urinary tract dysfunction (LOE 1, GOR A). Spontaneous voiding and/or intermittent catheterization must be considered in appropriate patients once they are medically stable (LOE 3, GOR A). Antimuscarinics are the first-line and intradetrusor botulinum toxin A injections are the second-line treatment for neurogenic detrusor overactivity (LOE 1, GOR A). Irreversible surgical interventions should be delayed until the second year after injury due to the potential for neurological recovery (LOE 4, GOR B). CONCLUSIONS: Careful clinical assessment and pertinent urological testing including urodynamic investigation are necessary for appropriate counselling and treatment of new SCI patients.

Urodynamic measurements reflect physiological bladder function in rats.

AIMS: Our objective was to investigate and compare bladder function in rats assessed by metabolic cage and by urodynamic measurements in fully awake animals. METHODS: Bladder function of female Lewis rats was investigated in naïve animals by metabolic cage at baseline, 14-16 days after bladder catheter and external urethral sphincter electromyography electrode implantation in fully awake animals by urodynamics, and again by metabolic cage. RESULTS: Investigating the same animals (n = 8), voided volume, average flow, and duration of voiding were similar (P > 0.05) in naïve animals measured by metabolic cage and after catheter implantation by urodynamic measurements and by metabolic cage. In naïve animals measured by metabolic cage, voided volumes were significantly different in the light (resting phase) versus the dark (active phase) part of the 24 h cycle (mean difference 0.14 mL, 21%, P = 0.004, n = 27). CONCLUSIONS: Lower urinary tract function assessed by metabolic cage or by urodynamic meaurements in fully awake rats was indistinguishable. Thus, catheter implantation did not significantly change physiological bladder function. This shows that urodynamic measurements in awake animals are an appropriate approach to study lower urinary tract function in health and disease in animal models, directly paralleling the human diagnostic procedures.

Value of urodynamic findings in predicting upper urinary tract damage in neuro-urological patients: A systematic review.

AIM: The main goals of neurogenic lower urinary tract dysfunction (NLUTD) management are preventing upper urinary tract damage (UUTD), improving continence, and quality of life. Here, we aimed to systematically assess all available evidence on urodynamics predicting UUTD in patients with NLUTD. METHODS: A systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement was performed in March 2017. Only neuro-urological patients assessed by urodynamics were included. Any outcome of upper urinary tract function were evaluated. RESULTS: Forty-nine studies (1 randomized controlled trial, 9 prospective, and 39 retrospective case series) reported urodynamic data on 4930 neuro-urological patients. Of those, 2828 (98%) were spina bifida (SB) children. The total number of adults was 2044, mainly having spinal cord injury (SCI) (60%). A low bladder compliance was found in 568 (46.3%) and 341 (29.3%) of the paediatric and adult population, respectively. Hydronephrosis (HDN) was detected in 557 children (27.8%) in 19/28 studies and 178 adults (14.6%), mainly SCI, in 14/21 studies. Nine out of 30 multiple sclerosis (MS) patients affected by HDN (16.8%) showed low compliance in 4/14 studies. CONCLUSIONS: Patients with SB and SCI have a higher risk of developing UUTD (mainly reported as HDN) compared to those with MS. Reduced compliance and high DLPP were major risk factors for UUTD. Although our findings clarify the mandatory role of urodynamics in the management of NLUTD, standardization and better implementation of assessments in daily practice may further improve outcomes of neuro-urological patients based on objective measurements, that is, urodynamics.

Catheterization for treating neurogenic lower urinary tract dysfunction in patients with multiple sclerosis: A systematic review. A report from the Neuro-Urology Promotion Committee of the International Continence Society (ICS).

AIM: To systematically assess all available evidence on efficacy and safety of catheterization for treating neurogenic lower urinary tract dysfunction (NLUTD) in patients with multiple sclerosis (MS). METHODS: This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies were identified by electronic search of Embase, Medline, Scopus, Cochrane register (last search March 3, 2018) and by screening of reference lists and reviews. RESULTS: After screening 7'015 articles, we included four studies (one prospective and two retrospective cohort studies, one retrospective cross-sectional study), in which a total of 445 patients were enrolled. No randomized controlled trial was available. Catheterization substantially increased quality of life, post void residual, and incontinence episodes in all included studies. Pooling of data for meta-analysis was not possible due to the heterogeneity of reported outcomes. Adverse events were reported in two studies only. Risk of bias and confounding was intermediate. CONCLUSIONS: Preliminary data suggests beneficial effects of catheterization on the urological outcome in patients with MS. However, although intermittent and indwelling catheterization is used frequently in daily clinical practice in the MS population, the evidence base is very limited and well-designed, properly sampled, and powered studies are urgently needed.