MP59-14 DIFFERENTIAL NEUROACTIVATION DURING INVOLUNTARY BLADDER CONTRACTIONS IN PONS VS BASAL GANGLIA STROKE SURVIVORS

PD07-05 VOLITIONAL AND INVOLUNTARY DETRUSOR CONTRACTIONS IN STROKE PATIENTS COMPARED TO VOLITIONAL CONTRACTIONS IN HEALTHY SUBJECTS: AN FMRI STUDY

To evaluate the efficiency of behavioral and drug therapy aimed at reducing the severity of storage symptoms, and to determine the influence of therapy with an anticholinergic drug and a beta-3-adrenergic receptor agonist on the severity of lower urinary tract symptoms (LUTS) and urodynamic parameters in patients with LUTS that persist after surgical treatment of benign prostatic hyperplasia (BPH). A total of 115 patients with detrusor overactivity and LUTS that persisted one month after surgical treatment of BPH (IPSS score of 8 or more) were included in the study. Preoperatively, these patients, in addition to a standard examination, underwent urodynamic study (UDS), which revealed concomitant detrusor overactivity. Surgical procedures included transurethral resection of the prostate, endoscopic enucleation of the prostate gland (laser or bipolar), retropubic or laparoscopic simple prostatectomy. At inclusion in the study, patients were randomized into three groups. In group 1 (n=39), behavioral therapy was recommended. In Group 2 (n=39), M-anticholinergic (Solifenacin 5 mg once a day) was administered, while in Group 3 (n=37) a beta-3-adrenergic receptor agonist (Mirabegron 50 mg) was used. After two months of therapy, patients underwent repeated UDS and the severity of LUTS was assessed using the IPSS questionnaire. After two months of therapy, in each group a significant decrease in the total IPSS score, the sum of the storage and voiding symptom scores, and the median Quality of Life (QoL) score was achieved (p<0.05). At the same time, in groups with drug treatment a lower average IPSS and storage symptom scores (7.7+/-3.6 and 5.8+/-2.3 for the behavioral therapy group, 6.1+/-2.7 and 4.3+/-2.1 for the M-anticholinergic group, 6.3+/-3.1 and 4.5+/-2.2 for the beta-3 agonist group, respectively, p<0.05 when comparing the behavioral therapy group with each of the drug therapy groups) was seen. According to the control UDS, detrusor overactivity persisted in 97.4% of patients in the behavioral therapy group, 89.7% in the M-anticholinergic group, and 91.9% in the beta-3 agonist group. In each group, a significant (p<0.05) increase in the maximum cystometric capacity, volume of occurrence of the first involuntary bladder contraction, and a decrease in the maximum detrusor pressure during involuntary contraction were found. In each group, surgical treatment allowed to alleviate bladder outlet obstruction (BOO). In those who received M-anticholinergic drug and a beta-3-adrenergic receptor agonist, the maximum detrusor pressure during involuntary contraction was lower than with behavioral therapy (32+/-15.5 in the M-anticholinergic drug group vs. 33.9+/-15.2 in the beta-3-agonist group vs. 40.5+/-20.6 in the behavioral therapy group). According to the control UDS, the maximum cystometric capacity, volume of occurrence of the first involuntary bladder contraction, and the BOO index were comparable in all groups. Mirabegron caused side effects less frequently than Solifenacin; there were only 3 adverse events (8.1%) in the Mirabegron group and 11 (28.2%) in the Solifenacin group. The rate of refusal to continue therapy in patients taking beta-3-agonist (2.7%; n=1) was also lower than for Solifenacin (7.7%; n=3). The study demonstrated the high efficiency of behavioral therapy and monotherapy with M-anticholinergic and beta-3-agonist in the treatment of LUTS that persist after surgical treatment of BPH. At the same time, both options of drug therapy demonstrate significantly greater efficiency than behavioral therapy in reducing the severity of LUTS and storage symptoms in particular, as well as in reducing detrusor pressure during its involuntary contractions. Therapy with the beta-3-agonist Mirabegron has a better safety profile than therapy with the M-anticholinergic Solifenacin, which results in greater patient compliance.

Detrusor contractions can be classified as either volitional or involuntary. The latter are a hallmark of urge urinary incontinence. Understanding differences in neuroactivation associated with both types of contractions can help elucidate pathophysiology and therapeutic targets. In this study we aim to compare brain activity associated with voluntary and involuntary detrusor contractions. Twenty seven stroke survivors with secondary storage lower urinary tract symptoms underwent four filling cycles of simultaneous urodynamics and BOLD-signal fMRI. After each fill, participants were instructed to void. Voids inside the designated 10-s period were considered voluntary contractions. All others were considered involuntary. Each contraction was then segmented into phases: Early (10 s before start of contraction), Rise (start of contraction to peak vesical pressure), Plateau, and Fall (from peak pressure to resolution of the contraction). BOLD-effect was compared between the two contraction types, employing a minimum cluster size of 25 voxels and significance threshold at p < 0.005. Compared to volitional contractions, involuntary contractions were associated with diminished brain activity in each contraction phase. During the Early phase, this difference was most prominent in areas implicated with sensory and autonomic function, shifting to regions tasked with motor control as the contraction continued and eventually attenuating as the contraction resolved. This study uniquely contrasts brain activation associated with volitional and involuntary contractions. Relative to involuntary contractions, volitional contractions revealed increased activity in motor, sensory, and executive functioning regions. These findings reflect both the physiological mechanism of volitional contractions and suggest the displacement of this mechanism by a subcortical reflex in involuntary contractions. NCT05301335.

PD43-02 A FUNCTIONAL MRI STUDY OF VOLUNTARY AND INVOLUNTARY DETRUSOR CONTRACTIONS IN STROKE PATIENTS

The aim of the study was to detect features of detrusor overactivity as an urodynamic phenomenon in patients with different etiology of low urinary tract dysfunction. Materials and methods The study included 283 patients (61% females and 39% males) aged 18-82 years (49.2+/-13.5) with neurogenic overactive bladder (n=197), idiopathic overactive bladder (n=41), radiation cystitis (n=8) and chronic pelvic pain (n=37). All patients underwent an urodynamic study (UDS) in Sverdlovsk Regional Clinical Hospital in the period from 2017 to 2020. Results Detrusor overactivity was detected by UDS in 63.4% patients with idiopathic, 94.2% with neurogenic overactive bladder (OAB) and 2.7% in patients with pelvic pain. Maximal amplitude of detrusor pressure during involuntary bladder contraction was significantly higher in neurogenic dysfunction than in idiopathic (25.76+/-26.21 cm 2 and 10.1+/-3.4 cm 2 respectively, =0.003). According to the ROC-analysis, detrusor pressure amplitude has a high predictor value in the diagnosis of a neurogenic origin of overactive bladder (AUC=0.863, p=0.045). The sensitivity of pressure more than 9.5 cm 20 was 88%. Bladder volume at the time of first involuntary contraction was 137+/-120 ml and 218+/-120 ml (=0.07) for neurogenic and idiopathic OAB respectively. Neurogenic detrusor overactivity followed by urgency incontinence more often than idiopathic (59.5% vs 19.2%). Conclusion Neurogenic detrusor overactivity is characterized by larger amplitude and higher rate of urgency incontinence.

Urinary incontinence after a stroke significantly affects patient outcomes and quality of life. It is commonly associated with uninhibited detrusor contractions, but the underlying neural mechanisms remain poorly understood. This study aimed to explore the brain activity patterns associated with volitional and involuntary bladder contractions in stroke survivors. This cohort study enrolled 15 stroke survivors with documented urinary incontinence and 9 healthy controls. Participants underwent simultaneous blood oxygen level-dependent functional magnetic resonance imaging of the brain and urodynamics, capturing 25 involuntary and 23 volitional bladder emptying events in patients with stroke and 35 volitional voiding events in healthy individuals. We used general linear modeling in functional magnetic resonance imaging analysis to discern neural activity patterns during these events and in the phases leading up to them, aiming to identify neural mechanisms underlying involuntary versus volitional urinary control. Statistical significance for neuroimaging analyses was set at P<0.005 with a minimum cluster size of 25 voxels. During volitional emptying events, both healthy controls and stroke survivors exhibited increases in activation in regions implicated in sensorimotor control and executive decision-making, such as the brainstem, cingulate cortex, prefrontal cortex, and motor areas. In contrast, involuntary emptying events were associated with minimal changes in brain activity, suggesting minimal cortical involvement. Bladder filling preceding volitional contractions was associated with activity in the salience network (insula, anterior cingulate gyrus) in stroke survivors and healthy controls. Conversely, although there was an increase in overall blood oxygen level-dependent signal, activation of the salience network was conspicuously absent during bladder filling preceding involuntary contractions. The findings suggest that the salience network plays an important role in maintaining urinary continence in stroke survivors. The inability to activate the salience network may underpin the pathophysiology of poststroke urinary incontinence. Interventions aimed at modulating this network could potentially ameliorate lower urinary tract symptoms in this patient population. URL: https://www.clinicaltrials.gov; Unique identifier: NCT05301335.

Objective. To compare bladder wall thickness in two kinds of urinary incontinent women—stress urinary incontinence (SUI) and overactive bladder (OAB) with urodynamic detrusor overactivity (DO), and to compare them with continent patients by ultrasound, also, correlate with cystometric results in incontinent women. Methods. 91 women were divided into the following groups: continent (n = 31), SUI (n = 30), and DO (n = 30) groups after clinical evaluation and urodynamic test (only in incontinent women). Transvaginal ultrasound was performed to the bladder wall thickness (BWT) measurement. The mean of BWT was calculated and data were analyzed with ANOVA and Turkey's multiple comparison tests. Pearson's correlation coefficient (r) was used to compare two variables. Receiver operating characteristic (ROC) curve was performed to study BWT as a diagnostic parameter. Results. BWT in DO group was significantly higher than that in the other groups (P < 0.005). A moderate positive correlation was found between BWT and maximum bladder pressure during involuntary bladder contraction. There was no difference in BWT between SUI and continent groups. DO group had lower first desire to void and cystometric capacity. Maximum bladder pressure at detrusor contraction had a moderate positive correlation with BWT. The ROC revealed an area under the curve of 0.962 (95% CI, 0.90–1.01). Conclusions. DO patients have increased bladder wall thickness, lower first desire to void, and lower cystometric capacity. There was a moderate correlation between BWT and maximum bladder pressure during involuntary bladder contraction.

MP63-05 NOVEL URODYNAMIC FINDINGS IN FEMALE PATIENTS WITH URGENCY URINARY INCONTINENCE

Near-Infrared Spectroscopy: A Novel, Noninvasive, Diagnostic Method for Detrusor Overactivity in Patients with Overactive Bladder Symptoms—A Preliminary and Experimental Study

Changes in detrusor muscle oxygenation during detrusor overactivity contractions

Describing bladder storage function: overactive bladder syndrome and detrusor overactivity

Background: Patients with urgency represent a group of incontinence sufferers whose diagnosis remains difficult to establish. Urodynamic testing demonstrating involuntary bladder contraction provides objective confirmation but represents an invasive approach. We have previously demonstrated that peripheral blood mononuclear cells (PBMC) can provide a reporter function in solid organ disease toward biomarker discovery. Here we investigated the utility of using PBMC as marker for patients with confirmed involuntary bladder contraction. Methods: Fifteen female patients were evaluated for involuntary bladder contractions and stress urinary incontinence as demonstrated by urodynamics and also assessed for pelvic prolapse, stress incontinence by history, bladder neck dysfunction, and bladder capacity. PBMC were obtained from patients’ whole blood, and RNA was subjected to microarray gene chip analysis. Results: Microarray analysis revealed that eleven genes were differentially regulated (five upregulated and six downregulated). Of these, PGRMC1 (progesterone receptor membrane component 1), EIF2S3 (eukaryotic initiation factor), C3AR1 (complement receptor), and three unknown genes were downregulated. Upregulated genes included MYOM2 (myomesin M-protein), a cytoskeletal protein; KTN1 (kinectin); and AAK 1 (AP2 associated kinase). Conclusions: Microarray analysis revealed many genes that were differentially regulated in PBMC from patients with involuntary detrusor contractions. These genes may be important in regulating structural integrity of bladder and supporting tissues. These data suggest that PBMC can provide a reporter function for patients with involuntary bladder contractions and may serve toward biomarker discovery for novel diagnostic markers and/or the ability to monitor response to therapy.

A Preliminary Study on the Impact of Detrusor Overactivity on the Efficacy of Selective Bladder Denervation for the Treatment of Female Refractory Overactive Bladder

To assess the prevalence of vesico-ureteral reflux (VUR) and upper urinary tract damage in women with idiopathic high-pressure detrusor overactivity (IHPDO) and to characterize their bladder function. A retrospective chart review of women diagnosed with IHPDO (detrusor pressures > 40 cm H2O during involuntary bladder contractions) from 2007 to 2010 was conducted. Women were assessed for VUR by X-ray voiding cysto-urethrogram. Renal ultrasound or CT urogram, serum BUN/creatinine, and urinalyses were performed if reflux reached the renal pelvices. Cystometric and voiding pressure study data were reviewed for detrusor overactivity pressure and volume, voiding dysfunction, urethral relaxation, compliance, and bladder outlet obstruction. Sixty-five women were diagnosed with IHPDO, and 50 completed an X-ray voiding cysto-urethrogram. The median (range) detrusor overactivity pressure was 65 (41-251) cm H2O. Four (8.0%) women had IHPDO; none had upper urinary tract deterioration. The majority of women exhibited urethral relaxation with voiding, impaired compliance, and bladder outlet obstruction. Women with IHPDO are at risk of low-grade vesico-ureteral reflux. However, most women with IHPDO are likely protected from reflux by intermittent exposure to high detrusor pressures and the ability to decompress the bladder by urethral relaxation.

Neurogenic detrusor overactivity (NDO) is common in patients who suffer from multiple sclerosis (MS). When the usual pharmacological treatment fails, botulinum toxin type A (BTX-A) injections can be proposed. The safety and efficacy of this treatment are already well known, but only a few studies focus on its use in patients with MS. Seventy-one patients with MS underwent their first BTX-A injection for refractory NDO. They had clinical and urodynamic cystometry assessment before and three months after injection. The patients were divided in three groups according to treatment efficacy: full success (total urinary continence, no overactive detrusor), improvement, or total failure (urge incontinence and overactive detrusor). 77% of the patients had clinical improvement or full success of the treatment with a reduction of their urgency and incontinence. Significant urodynamic improvement after treatment was shown on different parameters: volume at first involuntary bladder contraction (p = 0.0000001), maximum cystometric capacity (p = 0.0035), maximum detrusor pressure (p = 0.0000001). 46% of the patients were in the "full success" group. 31% of the patients had a partial improvement. 23% of the patients had no efficacy of the treatment. Duration of MS was a predictive factor of treatment failure (p = 0.015). Despite that a full success was obtained in 46% of the cases, BTX-A injection therapy failed to treat refractory NDO in 23% of patients suffering from MS. Duration of the disease was a predictive factor for an inefficient treatment. The injection therapy should be considered as soon as oral anti cholinergic drugs fail to reduce NDO.