Neurogenic Lower Urinary Tract Symptoms Research Articles

Neurogenic Lower Urinary Tract Symptoms, Fatigue, and Depression-Are There Correlations in Persons with Multiple Sclerosis?

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.

Development of a Sham Protocol to Investigate Transcutaneous Tibial Nerve Stimulation in Randomised, Sham-Controlled, Double-Blind Clinical Trials.

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.

MP52-12 PREDICTING RESPONSE TO TRANSCUTANEOUS ELECTRICAL SPINAL CORD NEUROMODULATION BASED ON PRE-TREATMENT MICTURITION-ASSOCIATED BRAIN ACTIVITY IN STROKE SURVIVORS

You have accessJournal of UrologyCME1 Apr 2023MP52-12 PREDICTING RESPONSE TO TRANSCUTANEOUS ELECTRICAL SPINAL CORD NEUROMODULATION BASED ON PRE-TREATMENT MICTURITION-ASSOCIATED BRAIN ACTIVITY IN STROKE SURVIVORS Luis Alejandro Morales Ojeda, Veronica Stefania Montero Arcila, Rita Jen, Aidin Abedi, Priya Kohli, Sarah Ponce, David Chapman, Kay Jann, David Ginsberg, and Evgeniy Kreydin Luis Alejandro Morales OjedaLuis Alejandro Morales Ojeda More articles by this author , Veronica Stefania Montero ArcilaVeronica Stefania Montero Arcila More articles by this author , Rita JenRita Jen More articles by this author , Aidin AbediAidin Abedi More articles by this author , Priya KohliPriya Kohli More articles by this author , Sarah PonceSarah Ponce More articles by this author , David ChapmanDavid Chapman More articles by this author , Kay JannKay Jann More articles by this author , David GinsbergDavid Ginsberg More articles by this author , and Evgeniy KreydinEvgeniy Kreydin More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003300.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Stroke patients often develop lower urinary tract symptoms (LUTS) due to disruption in the brain centers that control micturition. Transcutaneous spinal cord stimulation (TSCS) is a novel neuromodulation approach that has been previously shown to improve LUT function in these patients. However, the characteristics of responders to TSCS have not been previously identified. In this study, we assessed micturition-related brain activity as a biomarker of responsiveness to TSCS therapy for LUT dysfunction secondary to stroke. METHODS: Twelve patients with stroke-related LUTS were enrolled to receive 12 weeks (24 sessions) of TSCS in a prospective cohort study. Patients underwent simultaneous blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) and urodynamics during their baseline evaluation. LUTS were assessed using the International Consultation on Incontinence Overactive Bladder (ICIQ-OAB) questionnaire before and after completing TSCS. Responders were defined as those who reported ≥60% reduction in the ICIQ-OAB score. BOLD signal during maximal urgency (defined as 10 seconds preceding a detrusor contraction) was compared between responders and non-responders using statistical parametric mapping (p<0.01, cluster size >25 voxels). Models were controlled for age, sex, and time since stroke. RESULTS: Of 12 patients enrolled in the study, six were defined as responders to therapy, reporting a mean decrease in ICIQ-OAB by 8.6±0.91 points (p<0.01). Responders exhibited significantly higher BOLD signals in 16 clusters, including left insula, left middle cingulate cortex, bilateral cuneus, left precuneus, left precentral gyrus, left inferior frontal gyrus, and right temporal gyrus. Nonresponders exhibited significantly higher BOLD signals in 7 clusters centered in the corpus callosum and the basal ganglia. CONCLUSIONS: TSCS is a promising novel neuromodulation modality for the mitigation of neurogenic LUTS (NLUTS). Here we demonstrate that micturition-related brain activity may be a useful biomarker for predicting response to TSCS in patients with NLUTS secondary to stroke. Responders demonstrated higher BOLD signals in several cortical areas than non-responders, suggesting that a baseline level of brain activity may be necessary in order to have a successful outcome with TSCS. Source of Funding: Urology Care Foundation © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e707 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Luis Alejandro Morales Ojeda More articles by this author Veronica Stefania Montero Arcila More articles by this author Rita Jen More articles by this author Aidin Abedi More articles by this author Priya Kohli More articles by this author Sarah Ponce More articles by this author David Chapman More articles by this author Kay Jann More articles by this author David Ginsberg More articles by this author Evgeniy Kreydin More articles by this author Expand All Advertisement PDF downloadLoading ...

Treating Lower Urinary Tract Symptoms in Older Adults: Intravesical Options.

This article provides an overview of the diagnosis and the treatment of lower urinary tract symptoms in older adults complicated by the neurodegenerative changes in the micturition reflex and further confounded by age-related decline in hepatic and renal clearance raising the propensity of adverse drug reactions. The first-line drug treatment for lower urinary tract symptoms, orally administered antimuscarinics, fails to reach the equilibrium dissociation constant of muscarinic receptors even at their maximum plasma concentration and tends to evoke a half-maximal response at a muscarinic receptor occupancy of just 0.206% in the bladder with a minimal difference from exocrine glands, which raises the adverse drug reaction risk. On the contrary, intravesical antimuscarinics are instilled at concentrations 1000-fold higher than the oral maximum plasma concentration and the equilibrium dissociation constant erects a downhill concentration gradient that drives passive diffusion and achieves a mucosal concentration around ten-fold lower than the instilled concentration for a long-lasting occupation of muscarinic receptors in mucosa and sensory nerves. A high local concentration of antimuscarinics in the bladder triggers alternative mechanisms of action and is supposed to engage retrograde transport to nerve cell bodies for neuroplastic changes that underlie a long-lasting therapeutic effect, while an intrinsically lower systemic uptake of the intravesical route lowers the muscarinic receptor occupancy of exocrine glands to lower the adverse drug reaction relative to the oral route. Thus, the traditional pharmacokinetics and pharmacodynamics of oral treatment are upended by intravesical antimuscarinics to generate a dramatic improvement (~ 76%) noted in a meta-analysis of studies enrolling children with neurogenic lower urinary tract symptoms on the primary endpoint of maximum cystometric bladder capacity as well as the secondary endpoints of filling compliance and uninhibited detrusor contractions. The therapeutic success of intravesical multidose oxybutynin solution or oxybutynin entrapped in the polymer for sustained release in the pediatric populationbodes well for patients with lower urinary tract symptoms at the other extreme of the age spectrum. Though generally used to predict oral drug absorption, Lipinski's rule of five can also explain the ten-fold lower systemic uptake from the bladder of positively charged trospium over oxybutynin, a tertiary amine. Chemodenervation by an intradetrusor injection of onabotulinumtoxinA is merited for patients with idiopathic overactive bladder discontinuing oral treatment because of a lack of efficacy. However, age-related peripheral neurodegeneration potentiates the adverse drug reaction risk of urinary retention that motivates the quest of liquid instillation, delivering larger fraction of onabotulinumtoxinA to the mucosa as opposed to muscle by an intradetrusor injection can also probe the neurogenic and myogenic predominance of idiopathic overactive bladder. Overall, the treatment paradigm of lower urinary tract symptoms in older adults should be tailored to individual's overall health status and the risk tolerance for adverse drug reactions.

Differential transcriptomic changes in the central nervous system and urinary bladders of mice infected with a coronavirus.

Multiple sclerosis (MS) often leads to the development of neurogenic lower urinary tract symptoms (LUTS). We previously characterized neurogenic bladder dysfunction in a mouse model of MS induced by a coronavirus, mouse hepatitis virus (MHV). The aim of the study was to identify genes and pathways linking neuroinflammation in the central nervous system with urinary bladder (UB) dysfunction to enhance our understanding of the mechanisms underlying LUTS in demyelinating diseases. Adult C57BL/6 male mice (N = 12) received either an intracranial injection of MHV (coronavirus-induced encephalomyelitis, CIE group), or sterile saline (control group). Spinal cord (SC) and urinary bladders (UB) were collected from CIE mice at 1 wk and 4 wks, followed by RNA isolation and NanoString nCounter Neuroinflammation assay. Transcriptome analysis of SC identified a significantly changed expression of >150 genes in CIE mice known to regulate astrocyte, microglia and oligodendrocyte functions, neuroinflammation and immune responses. Two genes were significantly upregulated (Ttr and Ms4a4a), and two were downregulated (Asb2 and Myct1) only in the UB of CIE mice. Siglec1 and Zbp1 were the only genes significantly upregulated in both tissues, suggesting a common transcriptomic link between neuroinflammation in the CNS and neurogenic changes in the UB of CIE mice.

The Impact of Neurogenic Lower Urinary Tract Symptoms and Erectile Dysfunctions on Marital Relationship in Men with Multiple Sclerosis: A Single Cohort Study.

Aims: Multiple sclerosis (MS) is an autoimmune and neurodegenerative disease that is characterized by a great variety symptoms. Most MS patients suffer from neurogenic lower urinary tract symptoms (nLUTS) and erectile dysfunctions (ED). The aim this study is to assess the impact of nLUTS and ED on marital relationships in MS patients. Materials and Methods: MS male patients that arrived for our attention were prospectively enrolled in the study. All of the patients were evaluated on an Expanded Disability Status Scale (EDSS), an IIEF-5 for sexual function, an ICIQ-MLUTS for urinary function, and a Dyadic Adjustment Scale (DAS) for marital relationships. The data were analyzed using descriptive and inferential statistical tests in STATA/MP14. Results: The data of 57 male MS patients were eligible. The mean age was 45 (13.7) years, the mean disease duration was 15.49 (7.86) years, and the mean EDSS score was 3.5 (1.89). In total, 33 (57.89%) MS patients reported urine incontinence, of those, 24 (42.11%) reported UUI. The mean DAS score was 74.40 (34.58). The mean IIEF-5 score was 12.40 (8.05). The mean ICIQ-MLUTS score was 71.94 (41.06). The DAS and ICIQ-MLUTS scores were negatively correlated (r = −0.30, p < 0.001). The DAS and IIEF-5 were moderately correlated (r = 0.47, p < 0.001). The DAS and EDSS were strongly correlated (r = −0.72, p < 0.001). A univariate analysis showed that increasing age (p < 0.001), a longer disease duration (p = 0.029), a higher EDSS score (p < 0.001), and a higher ICIQ-MLUTS score (p < 0.001) were all significantly associated with lower DAS scores. Conclusions: This study demonstrated the large negative impact that nLUTS and ED due to MS have on patients’ marital relationships, highlighting the importance of a multidisciplinary approach in MS patients.

PD24-01 DIFFERENTIAL TRANSCRIPTOMIC CHANGES IN THE CENTRAL NERVOUS SYSTEM AND NEUROGENIC BLADDERS OF MICE INFECTED WITH A CORONAVIRUS

You have accessJournal of UrologyCME1 May 2022PD24-01 DIFFERENTIAL TRANSCRIPTOMIC CHANGES IN THE CENTRAL NERVOUS SYSTEM AND NEUROGENIC BLADDERS OF MICE INFECTED WITH A CORONAVIRUS Taylor Clarkson, Alison Xie, Naoko Iguchi, and Anna Malykhina Taylor ClarksonTaylor Clarkson More articles by this author , Alison XieAlison Xie More articles by this author , Naoko IguchiNaoko Iguchi More articles by this author , and Anna MalykhinaAnna Malykhina More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002566.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Neurodegenerative diseases, such as multiple sclerosis (MS), often lead to the development of neurogenic lower urinary tract symptoms (LUTS). We previously characterized neurogenic bladder dysfunction in a mouse model of MS induced by a coronavirus, mouse hepatitis virus (MHV). The objective of this study was to identify genes and pathways linking neuroinflammation in the central nervous system with urinary bladder dysfunction to enhance our understanding of the mechanisms underlying LUTS in demyelinating diseases. METHODS: Adult C57BL/6 male mice (N=12) received either an intracranial injection of MHV (6,000 PFU) or sterile saline (control). The lumbosacral (L6-S2) spinal cord (SC) segments and urinary bladders were collected during acute infection stage (week 1) and at the first peak of demyelination (week 4) after inoculation with the virus. Total RNA was isolated and analyzed using Nanostring nCounter Neuroinflammation panel. The expression levels of 770 genes associated with neuroinflammation were assessed and compared between the specimens. RESULTS: Transcriptome analysis of SC specimens confirmed a significantly increased expression of 132 genes in MHV mice (tens to hundreds fold change) involved in the regulation of astrocyte, microglia and oligodendrocyte functions, neuroinflammation and immune responses. Out of 132 genes up-regulated in the SC, only 2 genes (siglec1, 46-fold in the SC, 2.6-fold at 1 week and 1.8-fold at 4 weeks in the bladder; and zbp1, 568-fold in the SC, 2.8-fold at 1 week and 2.2-fold at 4 weeks in the bladder) were up-regulated in the urinary bladders of MHV-infected mice. Additionally, two genes were significantly up-regulated (ttr, 2.2-fold at 1week and 1.7-fold at 4 weeks; and ms4a4a, 2.3-fold at 1week and 1.6-fold at 4 weeks), and two were down-regulated (asb2, -1.8-fold at 1 week and -1.6-fold at 4 weeks, and myct1, -1.7-fold at 1week and -1.6-fold at 4 weeks) exclusively in the urinary bladders of MHV mice. CONCLUSIONS: Two genes, siglec1 (encodes type 1 transmembrane protein, expressed in microglia and macrophages, promotes neuroinflammation) and zbp1 (encodes a Z-DNA binding protein, plays role in the innate immune response) link the development of neuroinflammation in the central nervous system with neurogenic changes in the urinary bladders of MHV-infected mice. Further research is needed to establish a functional relationship between expression of these genes and neurogenic LUTS. Source of Funding: NIH/NIDDK R01 DK116648 (to A.M.) © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e415 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Taylor Clarkson More articles by this author Alison Xie More articles by this author Naoko Iguchi More articles by this author Anna Malykhina More articles by this author Expand All Advertisement PDF DownloadLoading ...

EDITORIAL COMMENT

This manuscript describes the very short-term effects of electrical pudendal nerve stimulation (EPNS) versus pelvic floor muscle training (PFMT) plus transanal electrical stimulation (TES) in Chinese men with urinary incontinence after radical prostatectomy. EPNS has been suggested for use in the management of stress urinary incontinence, urge urinary incontinence, urgency-frequency syndrome, and neurogenic lower urinary tract symptoms. In this parallel designed randomized controlled trial at a research institute and a university hospital, Chinese men with post-prostatectomy urinary incontinence were assigned to EPNS (64 patients) or PFMT plus TES (32 patients) and treated 3 times a week for 8 weeks.

Ideal Timing of Prostate Operation in Chronic Urinary Retention due to Benign Prostatic Hyperplasia by Serial Urodynamic Study: A Prospective Longitudinal Study

Introduction: Chronic Urinary Retention (CUR) due to prostatomegaly causes impaired detrusor function, secondary to obstruction-related changes in the bladder wall. Urodynamic study is the “gold standard” to determine detrusor function in CUR patients. Traditional management of all CUR patients due to Benign Prostatic Hyperplasia (BPH) is temporary catheter drainage of the urinary bladder, so that detrusor impairment may be corrected. There is no consensus regarding the ideal timing of prostate operation in Bladder Outlet Obstruction (BOO) patients presenting with CUR due to BPH. Aim: To assess the ideal timing of Transurethral Resection of the Prostate (TURP) in chronic urinary retention patients due to BPH. Materials and Methods: This was a prospective, longitudinal study of 57 eligible patients with non neurogenic lower urinary tract symptoms, who presented with chronic urinary retention due to benign prostatic hyperplasia and attended the Department of Urology, Institute of Post-Graduate Medical Education and Research and Seth Sukhlal Karnani Memorial Hospital (IPGME&amp;R SSKM) hospital, Kolkata, West Bengal, India from August 2019 to July 2022. Four serial Urodynamic Studies (UDS) were performed after initial catheterisation in sterile urine culture on the day 5, day 14, day 30, and at 6th week. As per UDS findings, patients were classified into Preserved Detrusor function group (n=18), at peak flow rate (Qmax) {Detrusor Pressure (Pdet) at peak flow rate} &gt;30 cm H2 O and Impaired Detrusor function group (n=39), Pdet at Qmax ≤30 cm H2 O. Descriptive statistics were performed as means, standard deviations and ranges using Microsoft Excel software. For categorical variables percentages were used. The Student’s paired-test and Chi-square test were used for statistical analysis. The p-value &lt;0.05 was considered statistically significant. Results: In the present study, mean age of preserved detrusor function group was 56.17 years and impaired detrusor function group was 67.08 years. In preserved detrusor function group (n=18), 83.3% patients had upper urinary tract changes and in impaired detrusor function group (n=39) only 15.4% patients had upper tract changes (p-value &lt;0.05). On the urodynamic study done 6 th week after initial catheterisation, in impaired detrusor function group, n=36 (92.30%) patients had Pdet at Qmax&gt;30 cm H2 O and only n=3 (7.7%) patients had Pdet at Qmax≤ 30 cm H2 O (p-value&lt;0.001). Conclusion: Urodynamic study is the gold standard to determine detrusor function in chronic urinary retention patients. It is ideal to wait till six weeks or beyond, for TURP in chronic urinary retention patients due to BPH after initial catheterisation.

The Sustained Therapeutic Effects of Percutaneous Posterior Tibial Nerve Stimulation in the Treatment of Neurogenic Lower Urinary Tract Symptoms in Patients with Parkinson's Disease: 24-months Clinical and Urodynamic Results

To determine the sustained therapeutic effect of percutaneous posterior tibial nerve stimulation (PTNS) treatment in Parkinson's disease patients with detrusor activity during 24 months. After 12 weeks therapy, PTNS was applied at 14-day intervals for 3 months, 21-day intervals for 3 months and 28-day intervals through 24 months. The patients completed a 3-day voiding diary and ICIQ-SF, OAB-V8, OAB-q SF questionnaires at 3rd, 6th, 9th,12th and 24th month. A total of 76 patients were enrolled in the study. Of these 44 (57.9%) were men and 32 (42.1%) women. The differences of compared parameters at baseline and at the end of 24 months were as follows; daytime frequency decreased by 4.6 voids daily, urge incontinence decreased by 4.2 episodes daily, urgency episodes decreased by 6.2 episodes daily, nocturia decreased by 2.4 voids (P <.001) and voided volume improved by a mean of 71.4 cc (P <.05). When compared with baseline significant improvements were seen in the volume at the first involuntary detrusor contraction (1st IDCV), maximum cystometric capacity (MCC), maximal detrusor pressure at first involuntary detrusor contraction (1st IDC Pdetmax), maximal detrusor pressure at MCC (MCC Pdetmax), detrusor pressure at maximal flow (PdetQmax) and post-void residual volume (PVR) after PTNS treatment at 3, 12, 24 months (P <.001 for each) except maximal flow rate (Qmax) value (P ˃.05). These results have demonstrated the significant improvements both on voiding and urodynamic parameters under PTNS treatment with a tapering protocol for during 24-months in Parkinson's disease with detrusor activity.

Lower urinary tract dysfunction in common neurological diseases.

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

Treatment of neurogenic lower urinary tract symptoms: main contributions from 2018 and 2019.

This review aims to update the studies involving the treatment of lower urinary tract symptoms (LUTS) in neurogenic patients, published in the last two years. Treatment of neurogenic LUTS (NLUTS) patients with β3 adrenoreceptor agonists was investigated in real-life conditions. A randomized controlled trial compared the efficacy of antimuscarinics versus onabotulinum toxin A in neurogenic patients. The use of desmopressin to treat nocturia in multiple sclerosis patients is also reported. The long-term treatment with BontA efficacy, its discontinuation, and possible strategies to maintain patients on treatment were also evaluated. Sacral neuromodulation and tibial nerve stimulation are continuously being evaluated in neurogenic patients, especially in the last years. The management of urinary tract infections and vesical lithiasis, two common complications in NLUTS patients, and the management of both these patients was assessed in clinical trials.A trial evaluating the use of the anti-Nogo-A antibody after a spinal cord injury to facilitate neuronal rewiring and prevent or improve NLUTS was reported for the first time.

MP48-16 COMPARATIVE EVALUATION OF WHITE MATTER DEMYELINATION BY MAGNETIC RESONANCE IMAGING AND NEUROGENIC VOIDING DYSFUNCTION IN A VIRAL MURINE MODEL OF MULTIPLE SCLEROSIS

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction (MP48)1 Apr 2020MP48-16 COMPARATIVE EVALUATION OF WHITE MATTER DEMYELINATION BY MAGNETIC RESONANCE IMAGING AND NEUROGENIC VOIDING DYSFUNCTION IN A VIRAL MURINE MODEL OF MULTIPLE SCLEROSIS Li Lu, Alison Xie, Natalie Serkova, and Anna Malykhina* Li LuLi Lu More articles by this author , Alison XieAlison Xie More articles by this author , Natalie SerkovaNatalie Serkova More articles by this author , and Anna Malykhina*Anna Malykhina* More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000903.016AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Lower urinary tract symptoms (LUTS) are present in 70–80% of patients with multiple sclerosis (MS), having a negative effect on the quality of the individual’s life. In 10–15% of patients, neurogenic LUTS are present at the onset of MS when there may be only few lesions identified in the CNS. In this study, we aimed to establish if early white matter demyelination could be detected by MRI, and whether it could be associated with the first signs of neurogenic LUTS. METHODS: Adult mice were inoculated with A59 strain of mouse hepatitis virus (coronavirus-induced encephalomyelitis model, CIE). The level of neurodegeneration was assessed by the Clinical Symptom Score (CSS). MRI experiments were performed on a 9.4 Tesla/ 20-cm BioSpec MRI scanner. Bladder function was evaluated in vivo by a filter paper assay, and in vitro by detrusor contractility studies. RESULTS: The spines from control and CIE mice (CSS≤1-2, 10 wks) were subjected to a FLASH MRI ultra-high resolution sequence, and DTI-EPI protocols. The mean diffusivity (D) and fractional anisotropy (FA) parameters were used to assess the integrity and organization of the white matter. The representative T2 MRI and DTI images, and FA maps are included in Fig. 1. The D values were significantly reduced in CIE mice (5.36±0.21x10-4 mm2/s) in comparison to control (6.98±0.37x10-4 mm2/s, p≤0.01). The FA parameters were also significantly lower in CIE mice (0.39±0.02 vs 0.56±0.02 in control, p≤0.002). Micturition patterns in CIE mice were not significantly changed, but the differences were detected in the contractile responses of the detrusor to various stimuli. CONCLUSIONS: The early changes in D and FA parameters reflect the ongoing changes in white matter structural integrity of the spinal cord. These early signs of demyelination are associated with modified detrusor contractile responses, which likely reflect the early stage of neurogenic LUTS development. Source of Funding: The study was supported by the NIH/NIDDK grant DK121506 and Department of Surgery AEF grant. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e700-e701 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Li Lu More articles by this author Alison Xie More articles by this author Natalie Serkova More articles by this author Anna Malykhina* More articles by this author Expand All Advertisement PDF downloadLoading ...

Historical and Current Concepts Regarding Urodynamics in Multiple Sclerosis Patients

In this review, current literature on management of neurogenic bladder in patients with multiple sclerosis (MS) is summarized. Topics include a review of MS, a brief overview of general treatment options, the effects of MS may manifest on lower urinary tract symptoms (LUTS), and clinical assessment of these patients. The utility of urodynamic evaluation in this patient population and the use of antibiotic prophylaxis in patients with MS on immunomodulatory medications are reviewed. Unlike neurogenic bladder in spinal cord patients, lower urinary tract dysfunction in MS patients rarely leads to upper urinary tract deterioration. Currently there is no consensus on imaging as a screening tool to assess renal deterioration in this patient population. Internationally, there are differing opinions on the necessity of performing invasive urodynamic (UDS) investigation in MS patients during initial assessment. However, UDS evaluation can be useful in the guidance of treatment options and patient counseling and prior to more invasive interventions. Depending on the severity of MS, lower urinary tract symptoms are common and can evolve with progression of the disease. Although individual guidelines exist for management of patients with MS and select aspects of neurogenic LUTS, an optimal guideline for initial evaluation and surveillance is not available. The evaluation of patients with MS reporting LUTS should be uniquely tailored and take into consideration individual symptoms, disease course, comorbidities, and medications. Additionally, MS patients on immunomodulation medications that undergo UDS should be considered for prophylactic antibiotics.

Sacral neuromodulation in congenital lumbo-sacral and traumatic spinal cord defects with neurogenic lower urinary tract symptoms: a single-center experience in children and adolescents.

This study evaluated sacral neuromodulation's effectiveness for managing refractory neuropathic lower urinary tract dysfunction in children and adolescents. Twenty-five children and adolescents underwent peripheral nerve evaluation test phase of sacral neuromodulation at our center. Thirteen (seven boys and six girls) cases suffered from neuropathic lower urinary tract dysfunction refractory to the maximum medical treatment. The test was done with temporary wire in all patients. Patients with more than 50% improvement in symptoms were chosen for the second stage of implantation of quadripolar tined lead and implantable pulse generator. Bowel transit symptoms were recorded before and after the surgery. Eight patients (61.53%; five boys and three girls) had positive responses to the peripheral nerve evaluation test phase. They underwent implantation of permanent quadripolar tined lead and implantable pulse generator. The etiologies were lumbosacral myelomeningocele, occult spina bifida, partial sacral agenesis and incomplete spinal cord injury. Positive clinical response (> 50% improvement in symptoms) was achieved in seven (85%) at a mean follow-up of 14.25months. Three patients became capable to stop clean intermittent catheterization (P =0.125). The 24-h pad test decreased from 484 to 78g from before to after the surgery (P =0.043). This clinical study on a small sample size of children and adolescents demonstrates positive results in short-term follow-up. However, as the procedure is still not approved officially, multicenter studies with more patients can prove the safety and efficacy of sacral neuromodulation in long term among this special group of patients.

The role of botulinum toxin A in the management of neurogenic lower urinary tract symptoms

Urinary incontinence associated with neurogenic detrusor overactivity is a common and distressing disorder in patients with chronic neurological conditions. When conservative therapy and antimuscarinic agents fail to treat or improve symptoms, intra-detrusor injections of botulinum toxin A may be considered. This article outlines the history of botulinum toxin A and its use in the management of neurogenic detrusor overactivity. Clinical issues such as patient selection, risks and benefits, and how to appropriately counsel patients prior to considering this treatment are discussed.

Clinical concomitant benefits on pelvic floor dysfunctions after sacral neuromodulation in patients with incomplete spinal cord injury

To assess the concomitant clinical improvement in incomplete spinal cord injury patients (SCIPs) suffering from neurogenic bowel symptoms (NBSs), neurogenic lower urinary tract symptoms (NLUTSs) and neurogenic erectile dysfunction (NED) using sacral neuromodulation (SNM) for NBSs and NLUTSs. Seventy-five SCIPs were selected. Before and during the follow-ups post-SNM, NLUTSs and NBSs were detected mainly through specific diaries. Erectile function was assessed using the International Index of Erectile Function composed of 5 questions (IIEF5). Quality of life (QoL) was measured with the Short Form 36 Health Survey questionnaire (SF-36). During the first stage, in which a permanent electrode was inserted percutaneously into the third sacral foramina and stimulated using an external generator, patients with NBSs or NLUTSs were required to improve their symptoms by at least 50% compared with baseline before proceeding to the second stage in which the generator was placed in the patient's buttock. NED patients needed to increase their IIEF5 score by at least 25% compared with baseline (evaluated initially 3 months after the second stage) in order to continue follow-up. Fourteen out of 37 subjects who manifested two functional pelvic dysfunctions at baseline maintained notable clinical improvement in two pelvic functions (median follow-up >3 years). Six had non-obstructive retention (NOR) and NED, six double incontinence, and two constipation with NOR. In the general and mental health domains of the SF-36, all patients improved their scores by at least 20% compared with baseline. SNM may be beneficial to selected incomplete SCIP with concomitant pelvic functional disturbances.

Clinical outcome of sacral neuromodulation in incomplete spinal cord injured patients suffering from neurogenic lower urinary tract symptoms

Clinical outcome of sacral neuromodulation in incomplete spinal cord injured patients suffering from neurogenic lower urinary tract symptoms

Clinical outcome of sacral neuromodulation in incomplete spinal cord injured patients suffering from neurogenic lower urinary tract symptoms

To determine the efficacy and safety of sacral neuromodulation (SNM) in incomplete spinal cord injured (SCI) subjects affected by neurogenic lower urinary tract symptoms (NLUTS). Twenty-four SCI patients were enrolled. The individuals were divided into two groups: 13 individuals in the urinary retention category and 11 suffering from overactive bladder syndrome. All subjects underwent definitive SNM implantation (Medtronic, Inc.). Voiding symptoms were assessed using patient bladder diaries, which recorded both pre-SNM and before each follow-up (1, 3 and 6 months, and then every 6 months). Outcome measures were per 24 h: number of voids and voided volume per void for both groups; number of urinary leakages, pad use and nocturia for patients with overactive bladder syndrome; and volume per catheterization and number of catheterizations for urinary retention subjects only. Final checkups were completed by June 2008. Median follow-up was 61 months. Up to the final visit, all subjects maintained a clinical improvement of more than 50% compared with baseline. Twenty-two side effects were recorded. Four subjects with urinary retention needed a new implant in the controlateral S3 sacral root because of loss of efficacy. One patient with urinary retention developed a wound infection at the implanted pulse generator site. Our study contains the largest series of implanted SCI patients ever published. SNM is a therapy to consider in the treatment of NLUTS for partial SCI patients, even if the loss of clinical benefits for patients with retentive NLUTS must be taken into account. All adverse events were treated effectively.