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Bench to Bedside in Neuro-Urology
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Bench to Bedside in Neuro-Urology

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Neurobiology and Clinical Neuroscience".

Deadline for manuscript submissions: closed (1 June 2023) | Viewed by 29491

Special Issue Editor

Prof. Dr. Thomas M. Kessler

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Guest Editor
Department of Neuro-Urology, Balgrist University Hospital, University of Zürich, Forchstrasse 340, 8008 Zürich, Switzerland
Interests: neuro-urology; functional urology; urinary tract infections
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The prevalence of neurogenic lower urinary tract, sexual and bowel dysfunction is high and affects the lives of millions of people worldwide. It not only has a major impact on people’s quality of life but also imposes a substantial economic burden on every healthcare system.

The control of lower urinary tract function is a complex, multilevel central and peripheral process; the associated neural network is distributed across parasympathetic, sympathetic and somatic pathways. Therefore, it is not surprising that in many neurological disorders, such as multiple sclerosis, Parkinson’s disease, stroke, spinal cord injury, spina bifida, diabetic neuropathy, Alzheimer’s disease, etc., lower urinary tract, sexual and bowel dysfunction is a frequent manifestation. The location and extent of the lesion in the neurological axis determines the dysfunction pattern, which is reflected in the patient’s symptoms. Indeed, the variability of neurogenic lower urinary tract dysfunction is huge and may range from a completely asymptomatic situation to end-stage renal failure that requires hemodialysis. In addition, the prevalence and incidence of several neurological disorders are already high, and neurodegenerative disorders such as Alzheimer’s disease will further increase in their prevalence and incidence due to the continuously aging population; so, increasing numbers of neurological patients will require professional neuro-urological management. This, however, can only be provided by adequately trained clinicians and enthusiastic researchers, as many questions regarding the neural control of lower urinary tract, sexual and bowel function and its alterations through the course of a neurological disorder remain unclear.

This Special Issue of Biomedicines focuses on studies conducted at the basic science, preclinical and clinical research levels in neuro-urology, and welcomes both original research articles and review papers.

Prof. Dr. Thomas M. Kessler
Guest Editor

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • neuro-urology
  • neurogenic lower urinary tract dysfunction
  • neurogenic sexual dysfunction
  • neurogenic bowel dysfunction
  • neurological disorders
  • preclinical research
  • therapeutic strategies
  • biomarkers
  • early diagnosis research

Published Papers (19 papers)

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Research

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17 pages, 2174 KiB  
Article
Differential Post-Translational Modifications of Proteins in Bladder Ischemia
by Han-Pil Choi, Jing-Hua Yang and Kazem M. Azadzoi
Biomedicines 2024, 12(1), 81; https://doi.org/10.3390/biomedicines12010081 - 28 Dec 2023
Viewed by 718
Abstract
Clinical and basic research suggests that bladder ischemia may be an independent variable in the development of lower urinary tract symptoms (LUTS). We have reported that ischemic changes in the bladder involve differential expression and post-translational modifications (PTMs) of the protein’s functional domains. [...] Read more.
Clinical and basic research suggests that bladder ischemia may be an independent variable in the development of lower urinary tract symptoms (LUTS). We have reported that ischemic changes in the bladder involve differential expression and post-translational modifications (PTMs) of the protein’s functional domains. In the present study, we performed in-depth analysis of a previously reported proteomic dataset to further characterize proteins PTMs in bladder ischemia. Our proteomic analysis of proteins in bladder ischemia detected differential formation of non-coded amino acids (ncAAs) that might have resulted from PTMs. In-depth analysis revealed that three groups of proteins in the bladder proteome, including contractile proteins and their associated proteins, stress response proteins, and cell signaling-related proteins, are conspicuously impacted by ischemia. Differential PTMs of proteins by ischemia seemed to affect important signaling pathways in the bladder and provoke critical changes in the post-translational structural integrity of the stress response, contractile, and cell signaling-related proteins. Our data suggest that differential PTMs of proteins may play a role in the development of cellular stress, sensitization of smooth muscle cells to contractile stimuli, and deferential cell signaling in bladder ischemia. These observations may provide the foundation for future research to validate and define clinical translation of the modified biomarkers for precise diagnosis of bladder dysfunction and the development of new therapeutic targets against LUTS. Full article
(This article belongs to the Special Issue Bench to Bedside in Neuro-Urology)
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10 pages, 482 KiB  
Article
Prevalence of Unfavorable Video-Urodynamic Findings and Clinical Implications in Patients with Minimally Conscious State/Unresponsive Wakefulness Syndrome: A Retrospective Descriptive Analysis
by Francois Leboutte, Christian Engesser, Leutrim Zahiti, Cyrill A. Rentsch, Helge Seifert, Ralf Anding, Margret Hund-Georgiadis, Sandra Möhr and Matthias Walter
Biomedicines 2023, 11(9), 2432; https://doi.org/10.3390/biomedicines11092432 - 31 Aug 2023
Cited by 1 | Viewed by 848
Abstract
The aim of this retrospective exploratory study was to investigate the prevalence of unfavorable findings during video-urodynamic studies (VUDS) in patients with minimally conscious state (MCS)/unresponsive wakefulness syndrome (UWS) and whether management of the lower urinary tract (LUT) was adjusted accordingly. A retrospective [...] Read more.
The aim of this retrospective exploratory study was to investigate the prevalence of unfavorable findings during video-urodynamic studies (VUDS) in patients with minimally conscious state (MCS)/unresponsive wakefulness syndrome (UWS) and whether management of the lower urinary tract (LUT) was adjusted accordingly. A retrospective chart review was conducted to screen for patients diagnosed with MCS/UWS at our rehabilitation center between 2011 and 2020. Patients 18 years or older were included and underwent baseline VUDS after being diagnosed with MCS/UWS. We analyzed urodynamic parameters and subsequent changes in LUT management in this cohort. In total, 32 patients (7 females, 25 males, median age 37 years) with MCS/UWS were included for analysis. While at least one unfavorable VUDS finding (i.e., neurogenic detrusor overactivity [NDO], detrusor sphincter dyssynergia {DSD, high maximum detrusor pressure during storage phase [>40 cmH2O], low-compliance bladder [<20 mL/cmH2O], and vesico–uretero–renal reflux [VUR]) was found in each patient, NDO (78.1%, 25/32) and DSD (68.8%, 22/32) were the two most frequent unfavorable VUDS findings. Following baseline VUDS, new LUT treatment options were established in 56.3% (18/32) of all patients. In addition, bladder-emptying methods were changed in 46.9% (15/32) of all patients, resulting in fewer patients relying on indwelling catheters. Our retrospective exploratory study revealed a high prevalence of NDO and DSD in patients with MCS/UWS, illustrating the importance of VUDS to adapt LUT management in this cohort accordingly. Full article
(This article belongs to the Special Issue Bench to Bedside in Neuro-Urology)
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10 pages, 1259 KiB  
Article
Functional Recovery after the Application of Amniotic Tissues and Methylene Blue during Radical Prostatectomy—A Pilot Study
by Dimitri Barski, Igor Tsaur, Mihaly Boros, Jan Brune and Thomas Otto
Biomedicines 2023, 11(8), 2260; https://doi.org/10.3390/biomedicines11082260 - 13 Aug 2023
Viewed by 1148
Abstract
Amniotic tissues and methylene blue (MB) provide the ability for neuroregeneration, and MB enables intraoperative neurostaining. We first combined the techniques to explore a neuroprotective effect on early functional outcomes in a retrospective proof-of-concept trial of 14 patients undergoing radical prostatectomy (RP). The [...] Read more.
Amniotic tissues and methylene blue (MB) provide the ability for neuroregeneration, and MB enables intraoperative neurostaining. We first combined the techniques to explore a neuroprotective effect on early functional outcomes in a retrospective proof-of-concept trial of 14 patients undergoing radical prostatectomy (RP). The patients were followed up at a median of 13 months, and the continence and potency rates were reported. Early recovery of continence was found after three months. No effect on potency was detected. The findings indicate the feasibility of this tissue-engineering strategy, and justify prospective comparative studies. Full article
(This article belongs to the Special Issue Bench to Bedside in Neuro-Urology)
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15 pages, 301 KiB  
Article
Neurogenic Lower Urinary Tract Symptoms, Fatigue, and Depression—Are There Correlations in Persons with Multiple Sclerosis?
by Anke K. Jaekel, Julius Watzek, Jörn Nielsen, Anna-Lena Butscher, Pirmin Zöhrer, Franziska Schmitz, Ruth K. M. Kirschner-Hermanns and Stephanie C. Knüpfer
Biomedicines 2023, 11(8), 2193; https://doi.org/10.3390/biomedicines11082193 - 4 Aug 2023
Cited by 1 | Viewed by 873
Abstract
The symptoms of multiple sclerosis (MS) frequently include fatigue, depression, and neurogenic lower urinary tract symptoms (LUTS), causing severe burdens on affected individuals. The relationships between these symptoms have not been intensively researched and there are no studies on the detailed influence of [...] Read more.
The symptoms of multiple sclerosis (MS) frequently include fatigue, depression, and neurogenic lower urinary tract symptoms (LUTS), causing severe burdens on affected individuals. The relationships between these symptoms have not been intensively researched and there are no studies on the detailed influence of the different neurogenic LUTS. We aimed to investigate the relationships between fatigue, depression, and neurogenic LUTS as recorded in bladder diaries by persons with MS. We analyzed the bladder diaries of 274 people and their scores on the Fatigue Scale for Motor and Cognitive Functions and the Centre for Epidemiologic Studies Depression Scale (German version). The neurogenic LUTS were defined as urgency, reduced voided volume, increased standardized voiding frequency, nocturia, and urinary incontinence. Those suffering from incontinence, nocturia, reduced voided volume, or urgency had higher fatigue scores compared to those without these symptoms. Those with nocturia showed significantly higher scores for depression. The severity of urgency and voided volume had the greatest effect on the severity of individuals’ fatigue and depression levels. With increasing urgency, the risk of clinically significant fatigue and depression was expected to increase. Urgency and voided volume correlated most with fatigue and depression. A prospective longitudinal study investigating fatigue/depression after the successful treatment of neurogenic LUTS is needed to clarify causality and offer possible treatment options for fatigue and depression. Full article
(This article belongs to the Special Issue Bench to Bedside in Neuro-Urology)
15 pages, 1781 KiB  
Article
Development of a Sham Protocol to Investigate Transcutaneous Tibial Nerve Stimulation in Randomised, Sham-Controlled, Double-Blind Clinical Trials
by Stephanie A. Stalder, Stéphanie van der Lely, Collene E. Anderson, Veronika Birkhäuser, Armin Curt, Oliver Gross, Lorenz Leitner, Ulrich Mehnert, Martin Schubert, Jure Tornic, Thomas M. Kessler and Martina D. Liechti
Biomedicines 2023, 11(7), 1931; https://doi.org/10.3390/biomedicines11071931 - 7 Jul 2023
Viewed by 1871
Abstract
Transcutaneous tibial nerve stimulation (TTNS) is a promising treatment for neurogenic lower urinary tract symptoms. However, the evidence is limited due to a general lack of randomised controlled trials (RCTs) and, also, inconsistency in the sham and blinding conditions. In the context of [...] Read more.
Transcutaneous tibial nerve stimulation (TTNS) is a promising treatment for neurogenic lower urinary tract symptoms. However, the evidence is limited due to a general lack of randomised controlled trials (RCTs) and, also, inconsistency in the sham and blinding conditions. In the context of much-needed RCTs, we aimed to develop a suitable sham-control protocol for a clinical setting to maintain blinding but avoid meaningful stimulation of the tibial nerve. Three potential electrode positions (lateral malleolus/5th metatarsal/plantar calcaneus) and two electrode sizes (diameter: 2.5 cm/3.2 cm) were tested to determine which combination provided the optimal sham configuration for a TTNS approach, based on a visible motor response. Sixteen healthy volunteers underwent sensory and motor assessments for each sham configuration. Eight out of them came back for an extra TTNS visit. Sensory thresholds were present for all sham configurations, with linear regression models revealing a significant effect regarding electrode position (highest at plantar calcaneus) but not size. In addition, motor thresholds varied with the position—lowest for the 5th metatarsal. Only using this position and 3.2 cm electrodes attained a 100% response rate. Compared to TTNS, sensory and motor thresholds were generally higher for the sham configurations; meanwhile, perceived pain was only higher at the lateral malleolus. In conclusion, using the 5th metatarsal position and 3.2 cm electrodes proved to be the most suitable sham configuration. Implemented as a four-electrode setup with standardized procedures, this appears to be a suitable RCT protocol for maintaining blinding and controlling for nonspecific TTNS effects in a clinical setting. Full article
(This article belongs to the Special Issue Bench to Bedside in Neuro-Urology)
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15 pages, 2126 KiB  
Article
The Microbiological Burden of Short-Term Catheter Reuse in Individuals with Spinal Cord Injury: A Prospective Study
by Tiev Miller, Dirk Lange, Jayachandran N. Kizhakkedathu, Kai Yu, Demian Felix, Soshi Samejima, Claire Shackleton, Raza N. Malik, Rahul Sachdeva, Matthias Walter and Andrei V. Krassioukov
Biomedicines 2023, 11(7), 1929; https://doi.org/10.3390/biomedicines11071929 - 7 Jul 2023
Cited by 2 | Viewed by 1318
Abstract
Despite the risk of developing catheter-associated urinary tract infections (CAUTI), catheter reuse is common among people with spinal cord injury (SCI). This study examined the microbiological burden and catheter surface changes associated with short-term reuse. Ten individuals with chronic SCI reused their catheters [...] Read more.
Despite the risk of developing catheter-associated urinary tract infections (CAUTI), catheter reuse is common among people with spinal cord injury (SCI). This study examined the microbiological burden and catheter surface changes associated with short-term reuse. Ten individuals with chronic SCI reused their catheters over 3 days. Urine and catheter swab cultures were collected daily for analysis. Scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) analyses were used to assess catheter surface changes. Catheter swab cultures showed no growth after 48 h (47.8%), skin flora (28.9%), mixed flora (17.8%), or bacterial growth (5.5%). Asymptomatic bacteriuria was found for most participants at baseline (n = 9) and all at follow-up (n = 10). Urine samples contained Escherichia coli (58%), Klebsiella pneumoniae (30%), Enterococcus faecalis (26%), Acinetobacter calcoaceticus–baumannii (10%), Pseudomonas aeruginosa (6%) or Proteus vulgaris (2%). Most urine cultures showed resistance to one or more antibiotics (62%). SEM images demonstrated structural damage, biofilm and/or bacteria on all reused catheter surfaces. XPS analyses also confirmed the deposition of bacterial biofilm on reused catheters. Catheter surface changes and the presence of antibiotic-resistant bacteria were evident following short-term reuse, which may increase susceptibility to CAUTI in individuals with SCI despite asymptomatic bacteriuria. Full article
(This article belongs to the Special Issue Bench to Bedside in Neuro-Urology)
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13 pages, 890 KiB  
Article
Urodynamics Are Essential to Predict the Risk for Upper Urinary Tract Damage after Acute Spinal Cord Injury
by Veronika Birkhäuser, Collene E. Anderson, Marko Kozomara, Mirjam Bywater, Oliver Gross, Stephan Kiss, Stephanie C. Knüpfer, Miriam Koschorke, Lorenz Leitner, Ulrich Mehnert, Helen Sadri, Ulla Sammer, Lara Stächele, Jure Tornic, Martina D. Liechti, Martin W. G. Brinkhof and Thomas M. Kessler
Biomedicines 2023, 11(6), 1748; https://doi.org/10.3390/biomedicines11061748 - 17 Jun 2023
Cited by 1 | Viewed by 1168
Abstract
We used clinical parameters to develop a prediction model for the occurrence of urodynamic risk factors for upper urinary tract (UUT) damage during the first year after acute spinal cord injury (SCI). A total of 97 patients underwent urodynamic investigation at 1, 3, [...] Read more.
We used clinical parameters to develop a prediction model for the occurrence of urodynamic risk factors for upper urinary tract (UUT) damage during the first year after acute spinal cord injury (SCI). A total of 97 patients underwent urodynamic investigation at 1, 3, 6, and 12 months after acute SCI, within the framework of a population-based longitudinal study at a single university SCI center. Candidate predictors included demographic characteristics and neurological and functional statuses 1 month after SCI. Outcomes included urodynamic risk factors for UUT damage: detrusor overactivity combined with detrusor sphincter dyssynergia, maximum storage detrusor pressure (pDetmax) ≥ 40 cmH2O, bladder compliance < 20 mL/cmH2O, and vesicoureteral reflux. Multivariable logistic regression was used for the prediction model development and internal validation, using the area under the receiver operating curve (aROC) to assess model discrimination. Two models showed fair discrimination for pDetmax ≥ 40 cmH2O: (i) upper extremity motor score and sex, aROC 0.79 (95% CI: 0.69–0.89), C-statistic 0.78 (95% CI: 0.69–0.87), and (ii) neurological level, American Spinal Injury Association Impairment Scale grade, and sex, aROC 0.78 (95% CI: 0.68–0.89), C-statistic 0.76 (95% CI: 0.68–0.85). We identified two models that provided fair predictive values for urodynamic risk factors of UUT damage during the first year after SCI. Pending external validation, these models may be useful for clinical trial planning, although less so for individual-level patient management. Therefore, urodynamics remains essential for reliably identifying patients at risk of UUT damage. Full article
(This article belongs to the Special Issue Bench to Bedside in Neuro-Urology)
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19 pages, 2008 KiB  
Article
Abnormal Resting-State Network Presence in Females with Overactive Bladder
by Ulrich Mehnert, Matthias Walter, Lorenz Leitner, Thomas M. Kessler, Patrick Freund, Martina D. Liechti and Lars Michels
Biomedicines 2023, 11(6), 1640; https://doi.org/10.3390/biomedicines11061640 - 5 Jun 2023
Cited by 1 | Viewed by 1143
Abstract
Overactive bladder (OAB) is a global problem reducing the quality of life of patients and increasing the costs of any healthcare system. The etiology of OAB is understudied but likely involves supraspinal network alterations. Here, we characterized supraspinal resting-state functional connectivity in 12 [...] Read more.
Overactive bladder (OAB) is a global problem reducing the quality of life of patients and increasing the costs of any healthcare system. The etiology of OAB is understudied but likely involves supraspinal network alterations. Here, we characterized supraspinal resting-state functional connectivity in 12 OAB patients and 12 healthy controls (HC) who were younger than 60 years. Independent component analysis showed that OAB patients had a weaker presence of the salience (Cohen’s d = 0.9) and default mode network (Cohen’s d = 1.1) and weaker directed connectivity between the fronto-parietal network and salience network with a longer lag time compared to HC. A region of interest analysis demonstrated weaker connectivity in OAB compared to HC (Cohen’s d > 1.6 or < −1.6), particularly within the frontal and prefrontal cortices. In addition, weaker seed (insula, ventrolateral prefrontal cortex) to voxel (anterior cingulate cortex, frontal gyrus, superior parietal lobe, cerebellum) connectivity was found in OAB compared to HC (Cohen’s d > 1.9). The degree of deviation in supraspinal connectivity in OAB patients (relative to HC) appears to be an indicator of the severity of the lower urinary tract symptoms and an indication that such symptoms are directly related to functional supraspinal alterations. Thus, future OAB therapy options should also consider supraspinal targets, while neuroimaging techniques should be given more consideration in the quest for better phenotyping of OAB. Full article
(This article belongs to the Special Issue Bench to Bedside in Neuro-Urology)
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12 pages, 4684 KiB  
Article
Onabotulinum Toxin A Intradetrusor Injections in Children with Neurogenic Lower Urinary Tract Dysfunction: Long-Term Histological Effects on the Bladder Wall
by Chiara Pellegrino, Valentina Forlini, Federica Lena, Maria Luisa Capitanucci, Francesca Diomedi Camassei, Enrico Castelli and Giovanni Mosiello
Biomedicines 2023, 11(5), 1300; https://doi.org/10.3390/biomedicines11051300 - 27 Apr 2023
Viewed by 1016
Abstract
Background: In the last twenty-five years, Onabotulinum Toxin A (BTX-A) has gained increasing popularity for neurogenic lower urinary tract dysfunction (NLUTD) treatment. To maintain its efficacy, repeated BTX-A intradetrusor injections are required over time, with unknown effects on the bladder wall in children. [...] Read more.
Background: In the last twenty-five years, Onabotulinum Toxin A (BTX-A) has gained increasing popularity for neurogenic lower urinary tract dysfunction (NLUTD) treatment. To maintain its efficacy, repeated BTX-A intradetrusor injections are required over time, with unknown effects on the bladder wall in children. The aim of this paper is to report long-term effects on the bladder wall in children treated with BTX-A. Methods: Children with NLUTD not responsive to anticholinergics were treated with BTX-A, according to our protocol, with bladder wall control using endoscopic cold-cup biopsy. Specimens were evaluated considering edema, chronic inflammation, and fibrosis. Results: Of the 230 patients treated from 1997 to 2022, we considered only specimens obtained in patients who had received ≥5 treatments (36 children), considered as the threshold to evaluate clinical effectiveness on long-term treatment with BTX-A. Most of them had congenital NLUTD (25 patients) and detrusor overactivity (27 patients). In all, increased edema and chronic inflammation with reduced fibrosis over time was reported; these data were not statistically significant. No difference was observed between patients with congenital and acquired diseases. Conclusions: Repeated intradetrusor BTX-A injections are not related to significant histological alterations in children, similarly with adults, and repeated injections could be considered safe. Full article
(This article belongs to the Special Issue Bench to Bedside in Neuro-Urology)
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9 pages, 1193 KiB  
Communication
Assessment of Brainstem Functional Organization in Healthy Adults and Overactive Bladder Patients Using Ultra-High Field fMRI
by Susana Fernández Chadily, Mathijs M. de Rijk, Janine M. W. Janssen, Job van den Hurk and Gommert A. van Koeveringe
Biomedicines 2023, 11(2), 403; https://doi.org/10.3390/biomedicines11020403 - 29 Jan 2023
Cited by 3 | Viewed by 1246
Abstract
The pathophysiological mechanisms of overactive bladder syndrome (OAB) remain largely unknown, with major involvement of the central nervous system (CNS). The periaqueductal gray (PAG) is a brainstem area which is indicated to play an essential role in bidirectional communication between the bladder and [...] Read more.
The pathophysiological mechanisms of overactive bladder syndrome (OAB) remain largely unknown, with major involvement of the central nervous system (CNS). The periaqueductal gray (PAG) is a brainstem area which is indicated to play an essential role in bidirectional communication between the bladder and the CNS. We aimed to assess consistency of PAG functional organization across different bladder sensory states in OAB patients. We propose, that PAG functional organization patterns across sensory states will differ between controls and OAB patients. We analyzed fMRI scans at 7 Tesla from six controls and two OAB patients. The Louvain module detection algorithm was applied to parcellate the PAG in empty and full bladder states. We assessed within-subject consistency and investigated differences in this consistency between both groups. High within-subject agreement of PAG parcellations between empty and full bladder states was demonstrated in both groups. Additionally, we showed that the correlations between PAG clusters in both bladder states were significantly different in patients compared to controls (p = 0.039). The methods introduced here offer a promising tool to assess functional organization of the PAG and understand the underlying pathology and the role of this region in OAB syndrome. Full article
(This article belongs to the Special Issue Bench to Bedside in Neuro-Urology)
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7 pages, 491 KiB  
Communication
Neuro-Urology: Call for Universal, Resource-Independent Guidance
by Glenn T. Werneburg, Blayne Welk, Marcio A. Averbeck, Bertil F. M. Blok, Rizwan Hamid, Michael J. Kennelly, Limin Liao, Stefania Musco, Pawan Vasudeva and Thomas M. Kessler
Biomedicines 2023, 11(2), 397; https://doi.org/10.3390/biomedicines11020397 - 29 Jan 2023
Cited by 3 | Viewed by 1687
Abstract
Neurogenic lower urinary tract dysfunction (NLUTD), the abnormal function of the lower urinary tract in the context of neurological pathology, has been the subject of multiple efforts worldwide for the development of clinical practice guidelines. These guidelines are based on the same body [...] Read more.
Neurogenic lower urinary tract dysfunction (NLUTD), the abnormal function of the lower urinary tract in the context of neurological pathology, has been the subject of multiple efforts worldwide for the development of clinical practice guidelines. These guidelines are based on the same body of evidence, and are therefore subject to the same gaps. For example, sexual and bowel dysfunction in the context of NLUTD, optimal renal function assessment in those who are non-ambulatory or with low muscle mass, optimal upper tract surveillance timing, and modification of diagnostic and treatment modalities for low-resource nations and communities are inadequately addressed. In addition, many aspects of the conclusions and final recommendations of the guidelines are similar. This duplicative work represents a large expenditure of time and effort, which we believe could be focused instead on evidence gaps. Here, we call for a global unified approach to create a single, resource-independent, comprehensive guidance on NLUTD, neurogenic sexual, and neurogenic bowel dysfunction. Targeted research addressing the evidence gaps should be called for and pursued. This will allow for focus to shift to filling the gaps in the evidence for future guidelines. Full article
(This article belongs to the Special Issue Bench to Bedside in Neuro-Urology)
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15 pages, 13286 KiB  
Article
Biofilms on Indwelling Artificial Urinary Sphincter Devices Harbor Complex Microbe–Metabolite Interaction Networks and Reconstitute Differentially In Vitro by Material Type
by Glenn T. Werneburg, Daniel Hettel, Ava Adler, Sromona D. Mukherjee, Scott D. Lundy, Kenneth W. Angermeier, Hadley M. Wood, Bradley C. Gill, Sandip P. Vasavada, Howard B. Goldman, Raymond R. Rackley, Daniel A. Shoskes and Aaron W. Miller
Biomedicines 2023, 11(1), 215; https://doi.org/10.3390/biomedicines11010215 - 14 Jan 2023
Cited by 2 | Viewed by 2136
Abstract
The artificial urinary sphincter (AUS) is an effective treatment option for incontinence due to intrinsic sphincteric deficiency in the context of neurogenic lower urinary tract dysfunction, or stress urinary incontinence following radical prostatectomy. A subset of AUS devices develops infection and requires explant. [...] Read more.
The artificial urinary sphincter (AUS) is an effective treatment option for incontinence due to intrinsic sphincteric deficiency in the context of neurogenic lower urinary tract dysfunction, or stress urinary incontinence following radical prostatectomy. A subset of AUS devices develops infection and requires explant. We sought to characterize biofilm composition of the AUS device to inform prevention and treatment strategies. Indwelling AUS devices were swabbed for biofilm at surgical removal or revision. Samples and controls were subjected to next-generation sequencing and metabolomics. Biofilm formation of microbial strains isolated from AUS devices was reconstituted in a bioreactor mimicking subcutaneous tissue with a medical device present. Mean patient age was 73 (SD 10.2). All eighteen artificial urinary sphincter devices harbored microbial biofilms. Central genera in the overall microbe–metabolite interaction network were Staphylococcus (2620 metabolites), Escherichia/Shigella (2101), and Methylobacterium-Methylorubrum (674). An rpoB mutation associated with rifampin resistance was detected in 8 of 15 (53%) biofilms. Staphylococcus warneri formed greater biofilm on polyurethane than on any other material type (p < 0.01). The results of this investigation, wherein we comprehensively characterized the composition of AUS device biofilms, provide the framework for future identification and rational development of inhibitors and preventive strategies against device-associated infection. Full article
(This article belongs to the Special Issue Bench to Bedside in Neuro-Urology)
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7 pages, 246 KiB  
Article
Intrathecal Baclofen for Spasticity: Is There an Effect on Bladder Function? Report of Three Cases and Review of the Literature
by Charalampos Konstantinidis, Eleni Moumtzi, Archodia Nicolia and Charalampos Thomas
Biomedicines 2022, 10(12), 3266; https://doi.org/10.3390/biomedicines10123266 - 16 Dec 2022
Viewed by 2081
Abstract
Introduction: traumatic brain injury (TBI) is very often associated with spasticity. Medical interventions may include medications such as baclofen, a Gamma-Aminobutyric Acid (GABA) -receptor agonist of poor lipid solubility. Intrathecal baclofen (ITB) administration is a contemporary treatment option which minimizes adverse effects in [...] Read more.
Introduction: traumatic brain injury (TBI) is very often associated with spasticity. Medical interventions may include medications such as baclofen, a Gamma-Aminobutyric Acid (GABA) -receptor agonist of poor lipid solubility. Intrathecal baclofen (ITB) administration is a contemporary treatment option which minimizes adverse effects in contrast with the oral form of the drug. Regarding low urinary tract dysfunction, TBI, as a suprapontine lesion, results in neurogenic detrusor overactivity. Frequency, urgency and urge incontinence are the predominant signs and symptoms of this condition. Our study aims to report the potential changes in bladder function in patients with spasticity, due to TBI, after the implantation of the baclofen pump and the control of spasticity. Material and Methods: We report three cases of TBI whose spasticity responded well to ITB. We evaluated our medical reports regarding bladder function retrospectively, before and after baclofen pump implantation. We compared the data of bladder diaries and urodynamic parameters. Results: Bladder function was improved in all patients. Regarding bladder diaries; the number of incontinence and micturition episodes was decreased and the volume per void was slightly increased. Regarding urodynamic parameters; bladder capacity and reflex volume increased, Pdetmax decreased, PVR was the same and DLPP was slightly decreased. Conclusions: Although the baclofen pump is implanted to treat spasticity, detrusor activity may be also affected. Therefore, patients’ urologic profiles should also be reevaluated after ITB. Further prospective studies are required to investigate the effect of ITB on bladder function in the clinical field and also at the basic science level. Full article
(This article belongs to the Special Issue Bench to Bedside in Neuro-Urology)
9 pages, 272 KiB  
Article
Neurogenic Lower Urinary Tract Dysfunction in Asymptomatic Patients with Multiple Sclerosis
by Anke K. Jaekel, Franziska I. Winterhagen, Federico L. Zeller, Anna-Lena Butscher, Franziska K. Knappe, Franziska Schmitz, Christopher Hauk, Johannes Stein, Ruth K. M. Kirschner-Hermanns and Stephanie C. Knüpfer
Biomedicines 2022, 10(12), 3260; https://doi.org/10.3390/biomedicines10123260 - 15 Dec 2022
Cited by 6 | Viewed by 1304
Abstract
Neurogenic lower urinary tract dysfunction (NLUTD) in asymptomatic patients with MS has been described in preliminary studies, but specific investigations of this topic are rare. Many authors advise early diagnosis and treatment of NLUTD in patients with MS. In contrast, clinical practice and [...] Read more.
Neurogenic lower urinary tract dysfunction (NLUTD) in asymptomatic patients with MS has been described in preliminary studies, but specific investigations of this topic are rare. Many authors advise early diagnosis and treatment of NLUTD in patients with MS. In contrast, clinical practice and different guidelines recommend neuro-urological diagnostics only in the presence of symptoms. Our aim was to investigate the characteristics of NLUTD and the correlations of clinical parameters with NLUTD in asymptomatic patients with MS. We evaluated bladder diaries, urodynamic findings, and therapy proposals. Correlations of the voided volume, voiding frequency, urinary tract infections, and uroflowmetry including post-void residual with the urodynamic findings were determined. In our study, 26% of the patients were asymptomatic. Of these, 73.7% had urodynamic findings indicative of NLUTD, 21.1% had detrusor overactivity, 13.2% had detrusor underactivity, 13.2% detrusor overactivity and detrusor sphincter dyssynergia, and 57.9% had radiologically abnormal findings of the bladder. No patients presented low bladder compliance or renal reflux. Clinical parameters from the bladder diary and urinary tract infections were found to be correlated with NLUTD, and the absence of symptoms did not exclude NLUTD in patients with MS. We observed that urinary tract damage is already present in a relevant proportion. Based on our results, we recommend that patients with MS be screened for NLUTD regardless of the subjective presence of urinary symptoms or the disease stage. Full article
(This article belongs to the Special Issue Bench to Bedside in Neuro-Urology)
8 pages, 475 KiB  
Article
Is EDSS Enough to Predict Risk of Upper Urinary Tract Damage in Patients with Multiple Sclerosis?
by Kevin Stritt, Ilaria Lucca, Beat Roth and Nuno Grilo
Biomedicines 2022, 10(12), 3001; https://doi.org/10.3390/biomedicines10123001 - 22 Nov 2022
Cited by 2 | Viewed by 997
Abstract
Lower urinary tract dysfunction is often observed in patients with multiple sclerosis (MS) and may be responsible for an increased risk of upper urinary tract (UUT) damage. Although there are well-known urodynamic risk factors for UUT damage, no clinical prediction parameters are clearly [...] Read more.
Lower urinary tract dysfunction is often observed in patients with multiple sclerosis (MS) and may be responsible for an increased risk of upper urinary tract (UUT) damage. Although there are well-known urodynamic risk factors for UUT damage, no clinical prediction parameters are clearly identified. We aimed to confirm the accuracy of the Expanded Disability Status Scale (EDSS) in predicting urodynamic risk factors for UUT deterioration and to assess other clinical parameters potentially predicting urodynamic risk factors. We retrospectively reviewed 201 patients with MS referred for primary neuro-urological work-up, including a video-urodynamic study (VUDS) from August 2009 to February 2020. Multivariate modeling revealed EDSS, male gender, and a number of LUTS as clinical parameters significantly associated with urodynamic risk factors for UUT damage (p = 0.06, p = 0.01, p = 0.02, respectively). A nomogram combining EDSS, male gender, and a number of different LUTS was created to predict the presence of at least one urodynamic risk factor for UUT damage. In conclusion, the presence of high EDSS combined with male gender and several different LUTS is significantly associated with urodynamic risk factors and can be used to stratify MS patients for further neuro-urological assessment and treatment. Full article
(This article belongs to the Special Issue Bench to Bedside in Neuro-Urology)
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Review

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13 pages, 1023 KiB  
Review
Prediction of Lower Urinary Tract, Sexual, and Bowel Function, and Autonomic Dysreflexia after Spinal Cord Injury
by Chiara Pavese and Thomas M. Kessler
Biomedicines 2023, 11(6), 1644; https://doi.org/10.3390/biomedicines11061644 - 6 Jun 2023
Cited by 2 | Viewed by 1798
Abstract
Spinal cord injury (SCI) produces damage to the somatic and autonomic pathways that regulate lower urinary tract, sexual, and bowel function, and increases the risk of autonomic dysreflexia. The recovery of these functions has a high impact on health, functioning, and quality of [...] Read more.
Spinal cord injury (SCI) produces damage to the somatic and autonomic pathways that regulate lower urinary tract, sexual, and bowel function, and increases the risk of autonomic dysreflexia. The recovery of these functions has a high impact on health, functioning, and quality of life and is set as the utmost priority by patients. The application of reliable models to predict lower urinary tract, sexual, and bowel function, and autonomic dysreflexia is important for guiding counseling, rehabilitation, and social reintegration. Moreover, a reliable prediction is essential for designing future clinical trials to optimize patients’ allocation to different treatment groups. To date, reliable and simple algorithms are available to predict lower urinary tract and bowel outcomes after traumatic and ischemic SCI. Previous studies identified a few risk factors to develop autonomic dysreflexia, albeit a model for prediction still lacks. On the other hand, there is an urgent need for a model to predict the evolution of sexual function. The aim of this review is to examine the available knowledge and models for the prediction of lower urinary tract, sexual, and bowel function, and autonomic dysreflexia after SCI, and critically discuss the research priorities in these fields. Full article
(This article belongs to the Special Issue Bench to Bedside in Neuro-Urology)
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25 pages, 1318 KiB  
Review
Assessing Neurogenic Lower Urinary Tract Dysfunction after Spinal Cord Injury: Animal Models in Preclinical Neuro-Urology Research
by Adam W. Doelman, Femke Streijger, Steve J. A. Majerus, Margot S. Damaser and Brian K. Kwon
Biomedicines 2023, 11(6), 1539; https://doi.org/10.3390/biomedicines11061539 - 26 May 2023
Cited by 1 | Viewed by 1807
Abstract
Neurogenic bladder dysfunction is a condition that affects both bladder storage and voiding function and remains one of the leading causes of morbidity after spinal cord injury (SCI). The vast majority of individuals with severe SCI develop neurogenic lower urinary tract dysfunction (NLUTD), [...] Read more.
Neurogenic bladder dysfunction is a condition that affects both bladder storage and voiding function and remains one of the leading causes of morbidity after spinal cord injury (SCI). The vast majority of individuals with severe SCI develop neurogenic lower urinary tract dysfunction (NLUTD), with symptoms ranging from neurogenic detrusor overactivity, detrusor sphincter dyssynergia, or sphincter underactivity depending on the location and extent of the spinal lesion. Animal models are critical to our fundamental understanding of lower urinary tract function and its dysfunction after SCI, in addition to providing a platform for the assessment of potential therapies. Given the need to develop and evaluate novel assessment tools, as well as therapeutic approaches in animal models of SCI prior to human translation, urodynamics assessment techniques have been implemented to measure NLUTD function in a variety of animals, including rats, mice, cats, dogs and pigs. In this narrative review, we summarize the literature on the use of animal models for cystometry testing in the assessment of SCI-related NLUTD. We also discuss the advantages and disadvantages of various animal models, and opportunities for future research. Full article
(This article belongs to the Special Issue Bench to Bedside in Neuro-Urology)
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11 pages, 1452 KiB  
Review
The Utility of Urodynamic Studies in Neuro-Urological Patients
by Andry Perrin and Jacques Corcos
Biomedicines 2023, 11(4), 1134; https://doi.org/10.3390/biomedicines11041134 - 9 Apr 2023
Cited by 2 | Viewed by 1747
Abstract
Introduction: The utility of a clinical tool lies in its clinical performance evaluation and describes the relevance and usefulness of that tool in a medical setting. The utility of urodynamic and video-urodynamic studies in the management of specific urodynamic profiles in the diagnosis, [...] Read more.
Introduction: The utility of a clinical tool lies in its clinical performance evaluation and describes the relevance and usefulness of that tool in a medical setting. The utility of urodynamic and video-urodynamic studies in the management of specific urodynamic profiles in the diagnosis, treatment, and prognostic approach in neuro-urological patients is the focus of the current review. Methods: For this narrative review, a PubMed® search was performed by cross-referencing the keywords “urodynamics”, “neurogenic bladder”, “utility”, “clinical utility” and “clinical performance” with various terms related to the management of neurogenic lower urinary tract dysfunction. Clinical practice guidelines and landmark reviews from the most renowned experts in the field were also used. Analysis: Assessment of the utility of urodynamic study was performed during the diagnostic, therapeutic and prognostic steps of the neuro-urological patients’ management. We focused on its clinical performance in the identification and evaluation of several unfavorable events, such as neurogenic detrusor overactivity, detrusor-sphincter dyssynergia, elevated detrusor leak point pressure and the presence of vesico-ureteral reflux, which may be indicators for a higher risk for the development of urological comorbidities. Conclusion: Despite the paucity of existing literature assessing the utility of urodynamic study—specifically video-urodynamic study—in neuro-urological patients, it does remain the gold standard to assess lower urinary tract function precisely in this patient category. With regard to its utility, it is associated with high clinical performance at every step of management. The feedback on possible unfavorable events allows for prognostic assessment and may lead us to question current recommendations. Full article
(This article belongs to the Special Issue Bench to Bedside in Neuro-Urology)
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Other

Jump to: Research, Review

8 pages, 552 KiB  
Brief Report
The Efficacy and Safety of Intrasphincteric Botulinum Toxin-A Injections in Patients with Non-Spinal Cord Injury-Related Detrusor Sphincter Dyssynergia: A Retrospective Study
by Kilian Röthlin, Ralf Anding, Helge Seifert, Margret Hund-Georgiadis, Sandra Möhr and Matthias Walter
Biomedicines 2023, 11(11), 3016; https://doi.org/10.3390/biomedicines11113016 - 10 Nov 2023
Viewed by 679
Abstract
Botulinum toxin-A (BoNT-A) injections into the external urethral sphincter are an established therapeutic procedure for reducing bladder outlet obstruction in patients with detrusor sphincter dyssynergia (DSD) due to spinal cord injury (SCI). Given the paucity of data on patients with DSD but without [...] Read more.
Botulinum toxin-A (BoNT-A) injections into the external urethral sphincter are an established therapeutic procedure for reducing bladder outlet obstruction in patients with detrusor sphincter dyssynergia (DSD) due to spinal cord injury (SCI). Given the paucity of data on patients with DSD but without SCI, we aimed to assess the efficacy of intrasphincteric BoNT-A injections in this cohort. For this retrospective study, we screened all patients who underwent their first intrasphincteric BoNT-A injection at our institution between 2015 and 2021. The inclusion criteria were patients aged 18 years or older with neurogenic detrusor overactivity (NDO) and DSD with a maximum detrusor pressure (Pdetmax) of >40 cmH2O, confirmed via video-urodynamic studies (VUDS). The primary outcome was a reduction in Pdetmax and detrusor overactivity leak point pressure (DOLPP) during NDO-associated urinary incontinence posttreatment. The secondary outcome was a reduction in patients relying on indwelling urinary catheters posttreatment. We included 13 eligible patients (all male, median age 31 years, with different underlying neurological disorders, except SCI). All underwent intrasphincteric BoNT-A injections with either 100 (n = 7) or 150 (n = 6) units, respectively. Pdetmax during voiding was significantly reduced posttreatment (median 105 vs. 54 cmH2O, p = 0.006), whereas DOLPP remained unchanged (i.e., median 50 cmH2O). While seven patients relied on indwelling urinary catheters pre-treatment, all were catheter-free posttreatment. Intrasphincteric BoNT-A injections in patients with non-SCI related DSD appear feasible for reducing bladder outlet obstruction to a certain degree in this cohort and subsequently for reducing the rate of indwelling catheters. Full article
(This article belongs to the Special Issue Bench to Bedside in Neuro-Urology)
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