Suprasacral Spinal Cord Injury Research Articles

Effect of electroacupuncture on urodynamics and Raf/MEK/ERK signaling pathway in spinal cord tissue of rats with detrusor hyperreflexia after suprasacral spinal cord injury.

To observe the effect of electroacupuncture (EA) on urodynamics and Raf/MEK/ERK signaling pathway in spine cord tissue of rats after suprasacral spinal cord injury (SSCI), so as to explore its possible mechanism in improving bladder function in rats with detrusor hyperreflexia after SSCI. Female SD rats were randomly divided into blank, sham operation, model, EA and EA+PD98059 groups, with 12 rats in each group. Thorax (T) 10 spinal cord transection was performed by surgery. Rats in the EA group were given EA (10 Hz/50 Hz, 20 min) at "Ciliao" (BL32), "Zhongji" (CV3), "Sanyinjiao" (SP6) and "Dazhui" (GV14) once daily for 7 d. Rats of the EA+PD98059 group received intraperitoneal injection of PD98059 (5 mg/kg) 2 h before EA intervention. The urodyna-mics was used to measure the base pressure, leak point pressure, maximum pressure, maximum capacity and comp-liance of bladder, and the morphology of bladder detrusor tissue was observed with HE staining. The TUNEL staining was used to detect the cell apoptosis of the spinal cord tissue. The expression levels of exchange protein directly activated by cAMP 2 (Epac2), Rap, phosphorylated rapidly accelerated fibrosarcoma (p-Raf), phosphorylated mitogen-activated extracellular signal-regulated kinase (p-MEK), phosphorylated extracellular signal regulated kinase 1 and 2 (p-ERK1/2), B-cell lymphoma-2 (Bcl-2), and Bcl-2 associated X protein (Bax) were determined by Western blot. Compared with the sham operation group, the base pressure, leak point pressure and maximum pressure of bladder were significantly increased (P<0.01), the maximum bladder capacity and bladder compliance were decreased (P<0.01), the cell apoptosis rate of spinal cord tissue was increased (P<0.01), and the expression levels of Epac2, Rap, p-Raf, p-MEK, p-ERK1/2, and Bcl-2 protein in spinal cord tissue were decreased (P<0.01), while the expression level of Bax protein was increased (P<0.01) in the model group. After the treatment and compared with the model group, the base pressure, leak point pressure and maximum pressure of bladder, the cell apoptosis rate of spinal cord tissue, the expression level of Bax protein were decreased (P<0.05) in the EA group, while the maximum bladder capacity and bladder compliance, the expression levels of Epac2, Rap, p-Raf, p-MEK, p-ERK1/2, and Bcl-2 protein in spinal cord tissue were all increased (P<0.05, P<0.01). In comparison with the EA group, the base pressure, leak point pressure and maximum pressure of bladder, the cell apoptosis rate, the expression level of Bax protein were significantly increased (P<0.05), whereas the maximum bladder capacity, bladder compliance, and the expression levels of p-MEK, p-ERK1/2, and Bcl-2 protein were decreased (P<0.05) in the EA+PD98059 group. Results of HE staining showed disordered transitional epithelial cells and destroyed lamina propria in bladder detrusor tissue, with the infiltration of monocytes in the model group, which was obviously milder in both EA and EA+PD98059 groups, especially in the EA group. EA can improve the bladder function in detrusor hyperreflexia rats after SSCI, which may be related to its effect in up-regulating Epac2 and Rap, activating the Raf-MEK-ERK pathway, and reducing the cell apoptosis of spinal cord tissue.

A Multielectrode Nerve Cuff for Chronic Velocity Selective Recording in a sheep model.

Supra-sacral spinal cord injury (SCI) causes loss of bladder fullness sensation and bladder over-activity, leading to retention and incontinence respectively. Velocity selective recording (VSR) of nerve roots innervating the bladder might enable identification of bladder activity. A 10-electrode nerve cuff for sacral nerve root VSR was developed and tested in a sheep model during acute surgeries and chronic implantation for 6 months. The cuff performed well, with 5.90±1.90 kΩ electrode, and <~800 Ω tissue impedance after 189 days implantation with a stable device and tissues. This is important information for assessing the feasibility of chronic VSR.Clinical Relevance-This demonstrates the manufacturing and performance of a neural interface for chronic monitoring of bladder nerve afferents with applications in urinary incontinence and retention management following SCI.

Underlying mechnism of electroacupuncture for treating detrusor hyperreflexia after suprasacral spinal cord injury through the PACAP-cAMP signaling pathway: 基于PACAP-cAMP信号通路研究电针治疗骶上脊髓损伤后逼尿肌反射亢进型膀胱的效应机制

ObjectiveTo elucidate the underlying mechanism and effect of electroacupuncture (EA) on the neurogenic bladder following suprasacral spinal cord injury (SSCI). A rat model of detrusor hyperreflexia after SSCI was established to examine the urodynamics, detrusor muscle tissue morphology, the protein and mRNA expression levels of pituitary adenylate cyclase activating peptide (PACAP) and its receptor PAC1R, and cyclic adenosine monophosphate (cAMP) content in the detrusor muscle with a focus on the PACAP-cAMP signaling pathway. MethodA total of 72 female SD rats were randomized into control group and sham operation group (n=12 per group) by using a random number table. The remaining 48 rats were established into the model of detrusor hyperreflexia after SSCI. After successful modeling, these rats were randomly assigned to model, EA, and EA + PACAP6-38 groups (n=12 per group). The unsuccessful modeled rats were used for exploratory observation. For the rats in EA group, “Ciliao (BL32)” “Zhongji (CV3)”, and “Sanyinjiao (SP6)” were needled and stimulated by EA. The PACAP receptor antagonist PACAP6-38 was administered intraperitoneally in the EA + PACAP6-38 group before EA, and EA was applied for seven consecutive days. After treatment, the urodynamics of the rats were analyzed, and hematoxylin and eosin staining was used to examine rat bladder detrusor tissue morphology. The expressions of PACAP-38 and PAC1R were detected by immunohistochemistry and Western blot. The mRNA expression levels of PACAP-38 and PAC1R were examined by RT-qPCR, while cAMP content was detected by ELISA. Results(1) Compared with sham operation group, it was exhibited disarray in the transitional epithelium cells of the bladder in the modeled rats. The intercellular space was significantly widened, accompanied by inflammatory cell infiltration and noticeable tissue edema. Both the bladder initial pressure and leak point pressure of the rats were higher (P < 0.01), whereas the maximum cystometric capacity and bladder compliance were lower (P < 0.01). The protein and mRNA expression levels of PACAP-38 and PAC1R in the detrusor muscle, together with the cAMP content, were lower (P < 0.05). (2) Compared with the model rats, the EA group showed reduced inflammatory response in the detrusor muscle tissue, with decreased monocyte infiltration and less severe tissue edema. The bladder smooth muscle cells exhibited increased integrity, and there was decreased cellular tissue edema, inflammatory cell infiltration, and fibroplasia. The bladder initial pressure and leak point pressure were lower (P < 0.05), while the maximum cystometric capacity and bladder compliance were higher (P < 0.01). The protein and mRNA expression levels of PACAP-38 and PAC1R in the detrusor muscle, along with the cAMP content, were higher (P < 0.05). (3) Compared to the EA group, the EA + PACAP6-38 group showed a less organized arrangement of muscle fibers in the detrusor muscle tissue, larger intercellular space, monocyte infiltration, and considerable tissue edema. The changes in bladder initial pressure and leak point pressure were not significant (P > 0.05), while the maximum cystometric capacity and bladder compliance were lower (P < 0.05). The changes in the protein and mRNA expressions of PACAP-38 within the detrusor muscle were not significant (P > 0.05), whereas the protein and mRNA expressions of PAC1R were reduced (P < 0.05), and the cAMP content within the detrusor muscle was lower (P < 0.05). ConclusionEA can ameliorate the uninhibited contractile condition of the detrusor muscle in the bladder following SSCI. By mediating the PACAP-cAMP signaling pathway, it reduces the pathological damage to the detrusor muscle, thereby improving bladder function.

MP52-20 OPTIMISATION OF TRANSCUTANEOUS SPINAL CORD STIMULATION IN MODULATION OF MICTURITION REFLEXES FOLLOWING SPINAL CORD INJURY

You have accessJournal of UrologyCME1 Apr 2023MP52-20 OPTIMISATION OF TRANSCUTANEOUS SPINAL CORD STIMULATION IN MODULATION OF MICTURITION REFLEXES FOLLOWING SPINAL CORD INJURY Hannah Houliston, Richard Nobrega, Natalia Vasquez, Frank Lee, and Sarah Knight Hannah HoulistonHannah Houliston More articles by this author , Richard NobregaRichard Nobrega More articles by this author , Natalia VasquezNatalia Vasquez More articles by this author , Frank LeeFrank Lee More articles by this author , and Sarah KnightSarah Knight More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003300.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Spinal cord injury (SCI) can result in neurogenic lower urinary tract dysfunction including neurogenic detrusor over-activity (NDO) and detrusor-sphincter dyssynergia (DSD). Exciting developments in spinal cord stimulation (SCS) have demonstrated potential to improve motor function. Transcutaneous SCS (tSCS) provides a non-invasive alternative to epidural SCS, and there is preliminary evidence to suggest it can modulate spinal networks involved in micturition. However, there is ambiguity regarding optimal electrode sites and stimulation parameters. The aim of this study was to investigate optimisation of electrode site and tSCS parameters during the filling and voiding phase of the micturition cycle in people with SCI. METHODS: Ethical approval was obtained from the Research Ethics Committee. Participants were recruited if they had a supra-sacral SCI and proven NDO on most recent urodynamics. During visit 1, 1 ms tSCS pulses of increasing amplitude where administered at three randomised electrode sites; cathode between spinous process of T11-12, or L1-2, anodes at iliac crests or abdomen. External anal sphincter (EAS) and bilateral tibialis anterior EMG were recorded throughout. Optimal electrode site was selected based on motor-evoked potential response, and tolerance to stimulation. With electrodes placed at the optimal site, tSCS was applied in 5 s bursts at either 1, 15 or 30 Hz during voluntary pelvic floor contraction, relaxation and control. During visit 2, participants completed 6 cycles of urodynamics, one control cycle at the start and end, two cycles applying either 30 or 15 Hz tSCS during bladder filling, and two cycles applying either 1 or 15 Hz tSCS during voiding. RESULTS: Six participants were recruited (4 male, 2 female), with mean age 50±20 years old. 4 had an incomplete cervical and 2 an incomplete thoracic SCI. All participants tolerated the stimulation, and there were no adverse events. Optimal electrode sites were cathode L1-2, anode abdomen (n=2), cathode T11-12, anode iliac crest (n=2), cathode L1-2, anode iliac crest (n=1) and cathode T11-12, anode abdomen (n=1). Preliminary analysis of EMG data indicates that tSCS may enhance voluntary contraction of EAS. In addition, tSCS during the filling phase may increase bladder capacity. Further analysis is on-going. CONCLUSIONS: tSCS is an exciting new development which may improve bladder and bowel function following SCI. Our initial studies optimising electrode positioning and parameters will be used to investigate the use of tSCS in a further study combining it with pelvic floor muscle training. Source of Funding: International Spinal Research Trust Grant © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e710 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hannah Houliston More articles by this author Richard Nobrega More articles by this author Natalia Vasquez More articles by this author Frank Lee More articles by this author Sarah Knight More articles by this author Expand All Advertisement PDF downloadLoading ...

Effects of repetitive functional magnetic stimulation in the sacral nerve in patients with neurogenic detrusor overactivity after suprasacral spinal cord injury: a study protocol for a randomized controlled trial

BackgroundNeurogenic detrusor overactivity (NDO) is a serious and common complication after spinal cord injury, affecting patients’ quality of life seriously. Therefore, we developed this research protocol to evaluate the efficacy of repetitive functional magnetic stimulation (rFMS) in the sacral nerve in patients with neurogenic detrusor overactivity (NDO) after suprasacral spinal cord injury (SCI) and provide more options for rFMS in treating NDO after suprasacral SCI.MethodsThis study is a single-center, randomized, parallel-group clinical trial. We will recruit the patients with NDO after suprasacral SCI in the Rehabilitation Department of the Affiliated Hospital of Southwest Medical University from September 2022 to August 2023. They will be assigned to the rFMS group and the sham stimulation group randomly. The sample size is 66, with 33 patients in each group. The rFMS group will receive real rFMS treatment of the sacral nerve (100% stimulation intensity, 5 Hz, 20 min each time, five times a week), and the sham group will receive sham stimulation. Both groups will receive similar treatment strategies, including medication, standard urine management, acupuncture treatment, and health education. The bladder compliance (bladder capacity/detrusor pressure) and pudendal nerve electromyography will be evaluated at baseline, 8th week of treatment. The residual volume of the bladder and bladder diary will be recorded once a week during 8 weeks of treatments. SCI-QOL and NBSS will be evaluated at baseline, the 4th and 8th week of treatment. In addition, the above assessments will be followed up at 8 weeks after the end of treatment.DiscussionIt is expected that the bladder function, symptoms, and quality of life might be significantly improved after rFMS of the sacral nerve.Trial registrationThe China Clinical Trials Registry has approved this study, registration number: ChiCTR2100045148. Registered on April 7, 2021.

Expression profiles of circular RNAs and interaction networks of competing endogenous RNAs in neurogenic bladder of rats following suprasacral spinal cord injury.

Neurogenic bladder (NB) following suprasacral spinal cord injury (SSCI) is an interstitial disease with the structural remodeling of bladder tissue and matrix over-deposition. Circular RNAs (circRNAs) are involved in fibrotic disease development through their post-transcriptional regulatory functions. This study aimed to use transcriptome high-throughput sequencing to investigate the process of NB and bladder fibrosis after SSCI. Spinal cord transection at the T10-T11 level was used to construct the SSCI model in rats (10-week-old female Wistar rats, weighing 200 ± 20 g). The bladders were collected without (sham group) and with (SSCI 1-3 groups) NB status. Morphological examination was conducted to assess the extent of bladder fibrosis. Additionally, RNA sequencing was utilized to determine mRNAs and circRNAs expression patterns. The dynamic changes of differentially expressed mRNAs (DEMs) and circRNAs (DECs) in different periods of SSCI were further analyzed. Bladder weight, smooth muscle cell hypertrophy, and extracellular matrix gradually increased after SSCI. Compared with the sham group, 3,255 DEMs and 1,339 DECs, 3,449 DEMs and 1,324 DECs, 884 DEMs, and 1,151 DECs were detected in the SSCI 1-3 groups, respectively. Specifically, circRNA3621, circRNA0617, circRNA0586, and circRNA4426 were significant DECs common to SSCI 1-3 groups compared with the sham group. Moreover, Gene Ontology (GO) enrichment suggested that inflammatory and chronic inflammatory responses were the key events in NB progression following SSCI. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment associated with the "Chemokine signaling pathway", the "IL-17 signaling pathway", and the "TGF-beta signaling pathway" suggests their potential involvement in regulating biological processes. The circRNA-miRNA-mRNA interaction networks of DECs revealed rno-circ-2239 (micu2) as the largest node, indicating that the rno-circ-2239-miRNA-mRNA-mediated network may play a critical role in the pathogenesis of SSCI-induced NB. This study offers a comprehensive outlook on the possible roles of DEMs and DECs in bladder fibrosis and NB progression following SSCI. These findings have the potential to serve as novel biomarkers and therapeutic targets.

Association of bladder trabeculation and neurogenic bladder with spinal cord injury

ObjectiveTo compare clinical findings and urodynamic parameters according to trabeculation grade and analyze their correlations with trabeculation severity in neurogenic bladder caused by suprasacral spinal cord injury (SCI).MethodsA retrospective chart review was performed of neurogenic bladder caused by SCI. Bladder trabeculation grade was compared with SCI-related clinical parameters and bladder-related urodynamic parameters.ResultsIn SCI patients, factors such as disease duration, bladder capacity, detrusor pressure, peak detrusor pressure values, and compliance were significantly different between different grades of bladder trabeculation, while neurological level of injury, completeness, and detrusor sphincter dyssynergia had no clear relationship with bladder trabeculation grade. In the correlation analysis, vesicoureteral reflux was moderately correlated with trabeculation grade (correlation coefficient 0.433), while the correlation coefficients of disease duration, involuntary detrusor contraction, and bladder filling volume were between 0.3 and 0.4.ConclusionBladder trabeculation with suprasacral-type neurogenic bladder was graded. Although disease duration was positively correlated with bladder trabeculation grade, differences in the neurological level of injury or American Spinal Injury Association Impairment Scale score were not observed. Bladder volume, peak detrusor pressure, compliance, reflex volume, and vesicoureteral reflux also showed significant differences according to trabeculation grade. Vesicoureteral reflux was moderately correlated with trabeculation grade.

Effect of moxibustion at "oppositely-located points" on neurogenic bladder after spinal cord injury and endoplasmic reticulum stress pathway in rats

To observe the effect of moxibustion at oppositely-located points "Mingmen" (GV 4) and "Shenque" (CV 8) on the motor function of the hind limbs and bladder function in rats with neurogenic bladder after suprasacral spinal cord injury (SCI), so as to explore the effect of this therapy on bladder tissue apoptosis mediated by endoplasmic reticulum stress pathway. Twenty-eight female Wistar rats were randomly divided into a sham-operation group (8 rats) and a model establishment group (20 rats). Using the modified Allen's method, the spinal cord of T10 segment was injured to establish a neurogenic bladder model in the model establishment group. Sixteen rats were modeled successfully and then divided into a model group (8 rats) and a moxibustion group (8 rats). In the moxibustion group, 2 h after consciousness regaining from modeling anesthesia, moxibustion was exerted at "Shenque" (CV 8) and "Mingmen" (GV 4), 2 cones at each acupoint in one intervention. The intervention was administered once every two days and 5-time intervention was required totally. After intervention, Basso, Beattie and Bresnahan locomotor rating scale (BBB) score for the motor function of the hind limbs, and the urodynamics indexes (maximum bladder capacity, urine leakage pressure and bladder compliance) were compared among groups. HE staining method was adopted to observe the morphological changes of bladder tissue. With Western blot method and real-time PCR assay, the protein and mRNA expressions of the endoplasmic reticulum stress-related genes (glucose- regulated protein 78 [GRP78], activating transcription factor 4 [ATF4] and cysteinyl aspartate specific proteinase-12 [Caspase-12]) were determined. The transitional epithelial cells were arranged irregularly, the bladder wall was getting thinner, and the cellular vacuolar degeneration and neutrophil infiltration were found in the model group. Whereas, compared with the model group, in the moxibustion group, the arrangement of transitional epithelial cells was clear and continuous in layers, the cellular vacuolar degeneration was mild and the infiltration presented in a small amount of neutrophil granulocytes. Compared with the sham-operation group, in the model group, the BBB score was reduced (P<0.01), the maximum bladder capacity and bladder compliance were increased (P<0.01), and the protein expression levels of GRP78, ATF4 and Caspase-12, as well as mRNA expressions were all increased (P<0.01). In comparison with the model group, in the moxibustion group, BBB score was increased (P<0.01), the maximum bladder capacity and bladder compliance were decreased (P<0.01), and the protein and mRNA expression levels of GRP78, ATF4 and Caspase-12 were all decreased (P<0.01). Moxibustion at the "oppositely-located points" improves the urination function, alleviate urine retention in neurogenic bladder rats after spinal cord injury. The underlying mechanism may be related to the down-regulation of the expressions of GRP78, ATF4 and Caspase-12 in the endoplasmic reticulum stress pathway of the bladder tissues, and thus to alleviate the apoptosis of bladder tissue.

Early interventions to prevent lower urinary tract dysfunction after spinal cord injury: a systematic review.

Systematic review. To synthetise the available scientific literature reporting early interventions to prevent neurogenic lower urinary tract dysfunction (NLUTD) after acute supra-sacral spinal cord injury (SCI). The present systematic review is reported according to the PRISMA guidelines and identified articles published through April 2021 in the PubMed, Embase, ScienceDirect and Scopus databases with terms for early interventions to prevent NLUTD after SCI. Abstract and full-text screenings were performed by three reviewers independently, while two reviewers performed data extraction independently. An article was considered relevant if it assessed: an in-vivo model of supra-sacral SCI, including a group undergoing an early intervention compared with at least one control group, and reporting clinical, urodynamic, biological and/or histological data. Of the 30 studies included in the final synthesis, 9 focused on neurotransmission, 2 on the inflammatory response, 10 on neurotrophicity, 9 on electrical nerve modulation and 1 on multi-system neuroprosthetic training. Overall, 29/30 studies reported significant improvement in urodynamic parameters, for both the storage and the voiding phase. These findings were often associated with substantial modifications at the bladder and spinal cord level, including up/downregulation of neurotransmitters and receptors expression, neural proliferation or axonal sprouting and a reduction of inflammatory response and apoptosis. The present review supports the concept of early interventions to prevent NLUTD after supra-sacral SCI, allowing for the emergence of a potential preventive approach in the coming decades.

Effect of electroacupuncture on urodynamics of neurogenic bladder and PACAP/cAMP/PKA signaling pathway in detrusor tissue of rats after suprasacral spinal cord injury

To observe the effect of electroacupuncture (EA) on urodynamics of neurogenic bladder and pituitary adenylate cyclase activating peptide(PACAP)/cyclic adenosine monophosphate (cAMP)/protein kinase A(PKA) signaling pathway in detrusor tissue of rats after suprasacral spinal cord injury (SCI), so as to explore its possible mechanism in improving detrusor hyperreflexia bladder function after shock stage of suprasacral SCI. Female SD rats were randomly divided into control, sham operation, model and EA groups, with 12 rats in each group. T10 spinal cord transection (SCT) was performed by surgery. Rats in the EA group were given EA (10 Hz/50 Hz, 20 min) at "Ciliao" (BL32), "Zhongji" (CV3) and "Sanyinjiao" (SP6) once daily for 7 days. After the intervention, urodynamics testing was detected in each group. HE staining was used to observe the morphological changes of bladder detrusor. The protein and mRNA expression of PACAP38 in detrusor was detected by immunohistochemistry, Western blot and real-time quantitive PCR, respectively. The contents of cAMP and PKA were determined by ELISA. Compared with the control and sham operation groups, the maximum bladder capacity and bladder com-pliance, and the protein and mRNA expression of PACAP38, and the contents of cAMP and PKA of the model group were significantly decreased (P<0.01, P<0.05), while the base pressure and leakage point pressure of bladder were significantly increased (P<0.01). After EA intervention, the above indexes were all reversed in the EA group relevant to those of the model group (P<0.01, P<0.05). EA at BL32, CV3 and SP6 can improve the bladder function in rats with bladder detrusor hyperreflexia after SCI, which may be related to its effect in activating the PACAP/cAMP/PKA signaling pathway in detrusor tissue.

A survey of clinical practice concerning long-term follow-up of neurogenic lower urinary tract dysfunction due to spinal cord injury in Italy

Context/objective This study aimed to assess the clinical practice for long-term follow-up (FU) of neurogenic lower urinary tract dysfunction (NLUTD) due to spinal cord injury (SCI) in Italy and compare this practice with the clinical practice in other countries and with the international guidelines. Design Data concerning the long-term urological FU of individuals with SCI were collected using a questionnaire and analyzed by means of descriptive and inferential statistics. Setting Twenty-one Italian centers following SCI patients. Participants One physician at each center (either a permanent staff member or chief). Outcome Measures Questions addressed the treatment of urinary tract infections (UTI), frequency of visits, urinary tract imaging examinations and urodynamic tests (UD), distinguishing between suprasacral and sacral SCI. Results Nineteen out of 21 centers completed the survey. In most centers, patients were recommended to undergo a visit and an ultrasound examination of urinary tract (UT) at least once a year. While the median interval between FU visits was identical (12 months) for individuals with suprasacral and sacral SCI, the two interval distributions were significantly different (suprasacral SCI: min–max 4–18, IQR = 6; sacral SCI: min–max 6–24; IQR = 8.5; P = 0.02), showing people with suprasacral SCI are followed up more often. Approximately 80% of the surveyed centers performed scheduled UD, with a yearly median frequency of 12 months (range 6–36) for patients with suprasacral SCI, as compared to a median frequency of 18 months for sacral SCI (range 0–36, P = 0.04). VideoUD and antibiotic prophylaxis for recurrent UTIs are carried out only by urologists in 63% and 47.4% of the centers, respectively. Overall, Italian centers share common strategies that compare to standards, including yearly visits, yearly UT examinations and stricter follow-up of people with suprasacral SCI, but may not have standard protocols for antibiotic prophylaxis of UTI, and in few cases control visits and UD are carried out too often. Conclusions Even though most Italian centers follow up patients with NLUTD secondary to SCI according to international guidelines, heterogeneity in frequency of FU examinations still exists. A tailored approach to the SCI patient that minimizes unnecessary examinations and groups different tests in a single access could improve patients’ compliance with FU and reduce costs for the Health system.

Urodynamic findings in patients with complete and incomplete suprasacral spinal cord injury at different stages after injury.

Urodynamics is the gold standard for evaluating the function of neurogenic bladder after spinal cord injury (SCI), but there are few studies on urodynamics in patients with complete and incomplete suprasacral SCI in different periods.There is a lack of sufficient evidence for the timing of the first urodynamic examination. The urodynamic results of 101 patients with complete and incomplete suprasacral SCI at 0-30, 31-60, 61-90, and 91-365 days after injury were included. Urodynamic parameters were compared between 0-90 and 91-365 days, including detrusor overactivity (DO), bladder compliance (BC), bladder-filling sensation, maximum cystometric capacity (MCC), detrusor external sphincter dyssynergia (DESD), maximum urinary flow rate (Qmax), detrusor pressure at a maximum urinary flow rate (PdetQmax). There were 45 patients with complete SCI and 56 with incomplete SCI. With the course's prolongation, the proportion of DO increased gradually in patients with complete and incomplete injury within 90 days, while the MCC gradually decreased. The bladder-filling sensation of patients with complete SCI is mostly absent. Significant differences were found between 0-90 and 91-365 days in terms of DO, DESD, MCC, Qmax, and PdetQmax incomplete SCI, and DESD in incomplete SCI, and between complete and incomplete SCI in terms of DO, bladder filling sensation, MCC, Qmax, PdetQmax at 0-90 days after injury, and bladder filling sensation at 91-365 days after injury. Urodynamic examination should be conducted as soon as possible after injury in patients with incomplete suprasacral SCI, while for those with complete injury, the urodynamic examination can be initiated following clinical symptoms within 90 days after injury.

Cardiovascular safety of mirabegron in individuals treated for spinal cord injury- or multiple sclerosis-induced neurogenic detrusor overactivity.

To analyze cardiovascular safety of mirabegron in patients with spinal cord injury (SCI)- and multiple sclerosis (MS)-induced neurogenic detrusor overactivity (NDO) in a prospective, randomized, double-blind, placebo-controlled study. Seventy-eight patients were enrolled into the study, and 66 of them were included into the final analysis. In 49 (74.2%), NDO developed due to suprasacral SCI, 17 (25.8%) suffered from NDO due to MS. Eleven patients were previously treated for hypertension and one for arrhythmia. All study participants received placebo for 2weeks run-in period. Subsequently, eligible subjects were randomized for 4weeks of active treatment with mirabegron 50mg once daily (Group A; n = 32) or placebo (Group B; n = 34). Data from resting electrocardiography (ECG), 24-h ECG and blood pressure monitoring, and echocardiographic examination, were used for cardiovascular safety assessment. All reported variables were evaluated at time of randomization and at the end of the study. Longitudinal changes of variables within the groups and differences between the groups were assessed using nonparametric Kruskal-Wallis test, and p ≤ 0.05 was considered statistically significant. No statistically significant longitudinal changes were found in safety variables, except for prolongation of QT interval in placebo group (p = 0.0328) recorded by resting ECG. No significant difference between the Groups A and B, in any of the variables, was observed. A single cardiovascular study drug-related adverse event was recorded in a patient with cervical SCI (3.13%). Our results suggest that mirabegron can be safely used in the treatment of patients with SCI- and MS-induced NDO.

Efficacy and safety of mirabegron for the treatment of neurogenic detrusor overactivity resulting from traumatic spinal cord injury: A prospective study.

To assess the clinical, urodynamic efficacy, and safety of mirabegron in patients with neurogenic detrusor overactivity (NDO) consequent to traumatic spinal cord injury (SCI). This prospective cohort study was performed between January 2018 and July 2019 and included adult patients with stable traumatic suprasacral SCI, performing clean intermittent catheterization (CIC), and demonstrating NDO on urodynamic study (UDS). A 3-day bladder diary was made at the baseline after which all patients were started on Mirabegron 50 mg. They were followed up at 6 weeks with a repeat bladder diary and UDS which were compared with those at the baseline. A total of 30 patients (4 females, 26 males, mean age: 30.07 years) were included. After 6 weeks of treatment, 5 out of the 29 incontinent patients became completely dry. The mean frequency of CIC decreased from 6.63 at the baseline to 5.37 at 6 weeks (p = .002), the mean CIC volume increased from 275 mlto 341 ml (p = .0002), the mean number of incontinence episodes in between CIC reduced from 3.97 to 2.27 (p < .0001) and time from CIC to leakage increased from 1.73 hto 2.75 h (p < .0001). The mean cystometric capacity increased from 348 ml to 406 ml (p = .008) and the maximum amplitude of NDO decreased from 54 cm H2 O to 41 cm H2 O(p = .005) at 6 weeks. Only two patients reported new onset dry mouth. No major adverse events were noted and none discontinued treatment. Mirabegron is efficacious and safe in patients with NDO consequent to traumatic SCI.

Incidence and predictive factors for developing vesicoureteric reflux in individuals with suprasarcral spinal cord injury: a historical cohort study.

A historical cohort study OBJECTIVES: The aim of the study was to examine the incidence of and predictive factors for VUR in individuals with suprasacral spinal cord injury (SCI). Srinagarind Hospital, Khon Kaen University, Thailand METHODS: Medical records were reviewed for all individuals with SCI and neurogenic bladder admitted for urological check-up between 1996 and 2016. The primary outcome was the cumulative incidence of VUR. The statistical tests used included the Nelson-Aalen Estimator and Cox Proportional Hazard Ratio. Harrell's C concordance statistic was used to evaluate the discrimination ability of the predictive model. 293 participants with SCI (102 tetraplegic and 191 paraplegic) were included. Most participants were male (67%), and the median age was 52 years. The overall incidence of VUR was 7.5 cases per 100 person-years (95% CI, 6.15-9.4). In the multivariate analysis, the predictive factors for VUR were: (1) maximum detrusor pressure at first visit ≥ 75 cm of water (HRadj: 2.4 [95% CI: 1.4-4.1]); (2) indwelling urethral catheterization (IUC) (HRadj: 11.1 [95% CI: 3.9-31.7]) and clean intermittent catheterization (CIC) (HRadj: 6.5 [95% CI: 2.2-18.7]); (3) age ≥ 60 years at onset of SCI (HRadj: 1.7 [95% CI: 1.1-2.8]); and, (4) absence of antimuscarinic medication (HRadj: 3.8 [95% CI: 2.4-6.1]). The predictive model had an overall C-index of 0.78. The incidence of VUR was high up to 12 years after SCI. High maximum detrusor pressure, IUC, age ≥ 60 years and absence of antimuscarinic medication were predictive factors for VUR.

Effects of electroacupuncture at different acupoints on the histomorphology of neurogenic bladder and the expression of hyperpolarization-activated cyclic nucleotide-gated channels in interstitial cells of Cajal in a rat model of suprasacral spinal cord injury.

To investigate the effects of electroacupuncture at different acupoints on the histomorphology of neurogenic bladder and the expression of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in interstitial cells of Cajal (ICC) in a rat model of suprasacral spinal cord injury (SCI). A incomplete suprasacral SCI rat model was induced using a MASCIS impactor. Rats were randomly divided into a sham operation group, SCI model group, Ciliao treatment group or Guanyuan treatment group. The histomorphology of bladder cells was observed after hematoxylin and eosin (H&E) staining of bladder tissue sections. The expression of HCN channel proteins in ICC cells was detected by western blot and immunofluorescence, and HCN channel mRNA expression was measured using real-time PCR. In terms of histomorphology, the level of bladder cells after SCI increased significantly, and marked inflammation and edema were observed. Electroacupuncture treatment at the Ciliao acupoint significantly reduced inflammation and edema, whilst electroacupuncture treatment at the Guanyuan point partially reduced inflammation and edema. In terms of HCN channel protein and mRNA expression, western blotting, immunofluorescence and real-time PCR all confirmed that HCN channel expression after SCI was significantly upregulated, while electroacupuncture treatment at the Ciliao and Guanyuan acupoints inhibited HCN channel expression. Electroacupuncture treatment at the Ciliao acupoint significantly reduced histomorphological abnormalities in ICCs, and inhibited the expression of HCN channel proteins after SCI.

Use of the ice water test as an early predictor of recovery of erectile function in patients with spinal cord injury.

Retrospective, cross-sectional. To determine the capacity of the ice water test (IWT) to predict erectile function during the early phase of spinal cord injury (SCI). France. This was a retrospective, cross-sectional study. Data from patients with SCI were included if they presented with neurogenic shock causing erectile dysfunction AND detrusor underactivity, and had undergone the following evaluations during the first 6 months post SCI (E1), and again at least 2 years later (E2): a complete neurological examination, urodynamic evaluation with the IWT, and evaluation by the Erection Hardness Score (EHS, from 0 to 4). Patients with cauda equina syndromes were excluded. Data from 62 patients with SCI were included, 37 with a positive IWT and 25 with a negative IWT. E1 was performed at 3.2 months ± 1.9, and E2 at 2.0 years ± 2.9 post SCI. At E2, 95% of patients with an initial positive IWT had reliable erections (EHS 3 or 4), compared with 0% of patients with a negative IWT. Neurogenic detrusor overactivity was found in 89% of patients with a positive IWT compared with 8% with a negative IWT. The IWT had a good sensitivity and negative predictive value: 100% for erectile function, and respectively 94 and 92% for bladder function. The IWT is a reliable and predictive test of erectile potential in patients with sacral and suprasacral SCI.

MP48-05 MULTIOMICS-BASED CHARACTERIZATION OF BLADDER REMODELING AFTER SPINAL CORD INJURY

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction (MP48)1 Apr 2020MP48-05 MULTIOMICS-BASED CHARACTERIZATION OF BLADDER REMODELING AFTER SPINAL CORD INJURY Ali Hashemi Gheinani*, Bryan S. Sack, Mary Piper, Hussein Atta, Justin F. Cotellessa, George Lambrinos, Kyle Costa, Claire Doyle, Susan Patalano, Vivian Cristofaro, Maryrose Sullivan, Jill A Macoska, and Rosalyn Adam Ali Hashemi Gheinani*Ali Hashemi Gheinani* More articles by this author , Bryan S. SackBryan S. Sack More articles by this author , Mary PiperMary Piper More articles by this author , Hussein AttaHussein Atta More articles by this author , Justin F. CotellessaJustin F. Cotellessa More articles by this author , George LambrinosGeorge Lambrinos More articles by this author , Kyle CostaKyle Costa More articles by this author , Claire DoyleClaire Doyle More articles by this author , Susan PatalanoSusan Patalano More articles by this author , Vivian CristofaroVivian Cristofaro More articles by this author , Maryrose SullivanMaryrose Sullivan More articles by this author , Jill A MacoskaJill A Macoska More articles by this author , and Rosalyn AdamRosalyn Adam More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000903.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Suprasacral spinal cord injury (SCI) is associated with profound remodeling of the bladder wall and with the development of neurogenic detrusor overactivity (NDO). However, the molecular pathways driving remodeling and how these contribute to functional alterations remain incompletely defined. The objective of this study was to use multi-omics approach to assess time-dependent transcriptional changes following SCI and to identify signaling pathways contributing to bladder wall remodeling and fibrosis. METHODS: Complete spinal cord transection at T8 was performed in male Sprague Dawley rats, with bladders harvested at 2, 8, and 16 weeks after injury. Age-matched, non-injured rats served as controls. Urine and blood were collected prior to sacrifice. RNA sequencing, small RNA sequencing, proteomics, phosphoproteomics was performed on full thickness bladder from rats from all time points. Urinary proteomics was also performed. Tissues were analysed by H&E staining as well as Masson’s trichrome staining (MTS) to assess the extent of fibrosis. RESULTS: Evaluation of bladder-to-body weight ratio revealed significant remodeling in bladders from SCI versus control rats. Quantification of MTS-stained slides showed a significant increase in collagen deposition in SCI versus controls at each time point. The intensity of changes reflected in biological functions showed an increase from 2 to 8 weeks but this increase was less enhanced from 8 to 16 weeks. Proteomics analysis indicated differential phosphorylation of actin cytoskeleton signaling, ILK signaling, RhoA signaling and Rho family GTPases signaling pathways in SCI compared to controls. The correlation between transcript levels and protein abundance was 25%. CONCLUSIONS: Our integrated, multi-omics analysis revealed perturbations in a variety of physiologically relevant pathways including those associated with innervation and cytoskeletal remodeling. These findings are consistent with the profound changes in bladder wall morphology following SCI. Integration of multiple omics datasets reveals novel insights into the pathogenesis of neurogenic bladder and implicates druggable kinases as regulators of pathologic remodeling. Source of Funding: R01 DK077195 © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e696-e696 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ali Hashemi Gheinani* More articles by this author Bryan S. Sack More articles by this author Mary Piper More articles by this author Hussein Atta More articles by this author Justin F. Cotellessa More articles by this author George Lambrinos More articles by this author Kyle Costa More articles by this author Claire Doyle More articles by this author Susan Patalano More articles by this author Vivian Cristofaro More articles by this author Maryrose Sullivan More articles by this author Jill A Macoska More articles by this author Rosalyn Adam More articles by this author Expand All Advertisement PDF downloadLoading ...

Role of Phosphodiesterase Inhibitors in Improving Urodynamic Parameters in Patients with Spinal Cord Injury: A Preliminary Report

Abstract Objective To analyze role of phosphodiesterase 5 (PDE5) inhibitors on urodynamic parameters in patients with suprasacral spinal cord injury. Materials and Methods This was a prospective observational hospital-based study conducted on a cohort of patients, aged between 18 and 65 years with suprasacral spinal cord injury, who were registered in Department of Neurosurgery/Urology. Cutoff period since injury was 2 years. After taking consent, baseline urodynamic study was performed, which was repeated 2 hours after taking single oral dose of 20 mg tadalafil. Urodynamic parameters such as maximum detrusor filling/voiding pressures, maximum bladder capacity, and bladder compliance before and after taking drug were compared for final results and conclusion. Results Following administration of 20 mg of tadalafil, maximum bladder capacity in mL showed statistically significant improvement from 268.39 ± 130.0 to 298.55 ± 112.0.(p &lt; 0.05). Bladder compliance improved from 18.68 ± 6.4 to 20.25 ± 7.5 mL/cm H2O (p &gt; 0.05). Maximum detrusor filling pressure improved from 36.03 ± 20.54 to 32.90 ± 16.47 cm H2O (p &gt; 0.05). Maximum detrusor voiding pressure improved from 64.65 ± 33.19 to 58.13 ± 20.7 cm H2O (0 &gt; 0.05). In patients with injury above D6 spinal cord level, statistically significant improvement was seen in maximum bladder capacity and bladder compliance after 2 hours of single oral dose of tadalafil (p &lt; 0.05). Conclusion Our study suggests a positive role of PDE inhibitors in improving urodynamic parameters in patients with suprasacral spinal cord injury with improvement in parameters such as bladder capacity, detrusor pressures, and bladder compliance. Because this is a small study group, more studies such as this are required to reach to final conclusion.

Urodynamic Differences between Complete and Incomplete Spinal Cord Injuries with Neurogenic Detrusor Overactivity

Objective: To analyze if there are urodynamic differences in patients with neurogenic detrusor overactivity (NDO) secondary to spinal cord injury (SCI) depending on whether the SCI is complete or incomplete according to the American Spinal Injury Association (ASIA) classification. Methods: A retrospective and comparative study was carried out, including 194 patients with suprasacral SCI and NDO. Maximum cystometric capacity (MCC), volume at first involuntary contraction (VIC), compliance, maximum pressure of the detrusor during filling cystometry (MaxDetP), detrusor leak point pressure (LeakDetP) and postvoid residual urine volume (PVR) were analysed. Means were compared with Student t test for independent samples, with statistical significance p < 0.05. Results: SCI was complete (ASIA A) in 51 patients (26.3%) and incomplete (ASIA B–E) in 143 (73.7%). The comparison of means showed significant differences regarding MCC (278.5 ± 102.6 mL in ASIA A vs. 321.6 ± 127.1 mL in ASIA B–E; p = 0. 018) and VIC (161 ± 85.1 and 210 ± 114.4 mL ­respectively; p = 0.006). There were no differences regarding MaxDetP (58.8 ± 26.9 vs. 49.3 ± 35.6 cm H₂O), LeakDetP (44.6 ± 25.3 vs. 48.3 ± 26.7 cm H₂O), PVR (155.3 ± 94.2 vs. 118.5 ± 129.8) or compliance (29.9 ± 25.3 vs. 48.3 ± 26.7 cm H₂O). Conclusions: In our serie incomplete SCI (ASIA B–E) showed differences from complete ones (ASIA A) regarding MCC and VIC, but not regarding LeakDetP, MaxDetP, PVR or compliance.