Christian Twiss

Increased Startle Responses in Interstitial Cystitis: Evidence for Central Hyperresponsiveness to Visceral Related Threat

PURPOSE Hypersensitivity to visceral stimuli in interstitial cystitis/painful bladder syndrome may result from enhanced responsiveness of affective circuits (including the amygdala complex) and associated central pain amplification. Potentiation of the eyeblink startle reflex under threat is mediated by output from the amygdala complex and, therefore, represents a noninvasive marker to study group differences in responsiveness in this brain circuit. MATERIALS AND METHODS Acoustic startle responses were examined in female patients with interstitial cystitis/painful bladder syndrome (13) and healthy controls (16) during context threat (application of muscle stimulation electrodes to the lower abdomen overlying the bladder), and cued conditions for safety (no stimulation possible), anticipation and imminent threat of aversive abdominal stimulation over the bladder. RESULTS Patients showed significantly greater startle responses during nonimminent threat conditions (baseline, safe and anticipation periods) while both groups showed similar robust startle potentiation during the imminent threat condition. Higher rates of anxiety and depression symptoms in the patient group did not account for the group differences in startle reflex magnitude. CONCLUSIONS Compared to controls, female patients with interstitial cystitis/painful bladder syndrome showed increased activation of a defensive emotional circuit in the context of a threat of abdominal pain. This pattern is similar to that previously reported in patients with anxiety disorders as well as those with irritable bowel syndrome. Since these circuits have an important role in central pain amplification related to affective and cognitive processes, these results support the hypothesis that the observed abnormality may be involved in the enhanced perception of bladder signals associated with interstitial cystitis/painful bladder syndrome.

Familial transmission of urogenital prolapse and incontinence.

Purpose of review To summarize recent evidence suggesting a genetic basis for the development of urogenital prolapse and stress urinary incontinence. Recent findings Epidemiological evidence suggests that some women have a genetic predisposition to the development of urogenital prolapse and stress incontinence. Abnormal expression of various structural proteins is thought to be the molecular genetic mechanism for the development of these conditions. A group of families with an autosomal dominant pattern of transmission of urogenital prolapse with high penetrance has been identified. No similar cohort of families with familial stress incontinence currently exists, although candidate genes have been identified that appear to predispose women to urogenital prolapse and stress incontinence. Additionally, animal models of urogenital prolapse have been developed that closely parallel the development of prolapse in humans. Summary A growing body of evidence suggests a genetic basis for the development of urogenital prolapse and stress incontinence. Candidate genes have been identified that may result in alteration of the normal metabolism of various structural proteins which may ultimately predispose some women to both urogenital prolapse and stress incontinence. Further research into the genetic basis of these conditions may provide a comprehensive understanding of the biological basis of these disorders.

A CONTINENCE INDEX PREDICTS THE EARLY RETURN OF URINARY CONTINENCE AFTER RADICAL RETROPUBIC PROSTATECTOMY

PURPOSE We evaluated the ability of a newly developed continence index to predict the return of urinary continence 3 months after radical retropubic prostatectomy. MATERIALS AND METHODS We developed and used a continence index to determine continence level after removal of the urinary catheter on postoperative day 15 in 145 men. A total of 20 patients were evaluated independently by 2 nurse specialists to assess continence index reliability. We evaluated continence level, pad use and degree of bothersomeness due to incontinence 3 months after catheter removal. The association of continence score with outcome variables was calculated using the Mantel-Haenszel trend test and the predictive ability of the continence score was determined by logistic regression to produce cumulative odds ratios. RESULTS The intraclass correlation coefficient was 0.995 for the independently assessed continence index ratings and the Cronbach coefficient alpha was 0.65 for the 5 continence index parameters. Complete continence or continence with heavy activity but not always was achieved by 96%, 85% and 68% of the men in tertiles 1 (continence score 18), 2 (continence score 15 to 17) and 3 (continence score 14 or less), respectively. The cumulative odds ratio of 2.9 (95% confidence interval [CI] 1.9 to 4. 6) per tertile indicated a 2.9-fold increased chance of incontinence for each successively lower tertile. In addition, 96%, 82% and 68% of the men in tertiles 1 to 3, respectively, required no or 1 small pad daily. The cumulative odds ratio for pad use was 2.3 (95% CI 1.5 to 3.5) per tertile. Of the patients in tertiles 1 to 3 100%, 97% and 80%, respectively, had no or slight bothersomeness due to urinary incontinence. The cumulative odds ratio for bothersomeness level was 2.7 (95% CI 1.7 to 4.3) per tertile. The Mantel-Haenszel trend test showed a significant association of continence score with all 3 outcome variables (p < or =0.001). CONCLUSIONS Our continence index is a simple and reliable instrument that provides useful prognostic information on the early return of continence after radical retropubic prostatectomy.

Painful Bladder Syndrome: An Update and Review of Current Management Strategies

Interstitial cystitis/painful bladder syndrome (IC/PBS) remains a prevalent, but untreated disease with a poorly understood pathophysiology. Nonetheless, four main processes currently appear to be involved in producing IC/PBS symptoms: (1) disruption of the bladder GAG/proteoglycan layer, (2) upregulated immune/inflammatory response, (3) neural upregulation, and (4) pelvic floor dysfunction. Current and emerging therapies aimed at these potential targets will be the focus of this review with an update on IC/PBS therapy.

Validating the Incontinence Symptom Severity Index: A Self-Assessment Instrument for Voiding Symptom Severity in Women

PURPOSE Most voiding symptom self-assessment instruments assess either symptom bother or effect on quality of life. The Incontinence Symptom Severity Index is an instrument for self-assessment of severity of female urinary storage and voiding symptoms, rather than symptom bother or effects of symptoms on quality of life. We assessed the validity of the Incontinence Symptom Severity Index for female voiding symptom self-assessment. MATERIALS AND METHODS The Incontinence Symptom Severity Index assesses 8 symptom domains, including emptying, urgency, urge incontinence, nocturia, daytime frequency, stress incontinence, leakage with physical activity and pad use. Three separate cohorts of women with a mean age of 59, 60 and 63 years, respectively, who underwent evaluation for urinary complaints associated with incontinence and vaginal prolapse were analyzed. Internal consistency was assessed via item-total correlations and Cronbachs alpha. Concurrent validity against the Urogenital Distress Inventory and Pelvic Floor Distress Inventory-Short Form were studied by correlating similar symptom domains of the Incontinence Symptom Severity Index with both instruments. We assessed criterion validity by comparison with the objective measures of post-void residual urine, voiding logs and self-reported pad use. Response to change was assessed by comparing pretreatment and posttreatment Incontinence Symptom Severity Index scores. RESULTS Significant item total correlations were seen for each Incontinence Symptom Severity Index item and Cronbachs alpha was 0.69. All Incontinence Symptom Severity Index items significantly correlated with similar items of the Urogenital Distress Inventory and Pelvic Floor Distress Inventory-Short Form. Significant posttreatment reductions were also observed for all 8 Incontinence Symptom Severity Index items. Progressively higher post-void residual urine was noted for the 4 severity scores of Incontinence Symptom Severity Index item 1 (emptying) (p = 0.07). Incontinence Symptom Severity Index items 3 (nocturia) and 4 (daytime frequency) showed significantly increasing nighttime and daytime voids with worsening severity scores for each (p <0.0001 and <0.0041, respectively). Incontinence Symptom Severity Index items 5 to 8 (stress incontinence, urge incontinence, leakage with activity and pad use) showed significantly increasing trends in mean daily pad use (p <0.0001, 0.022, <0.0001 and <0.0001, respectively) among the 4 severity scores for each. CONCLUSIONS The Incontinence Symptom Severity Index demonstrates good reliability and validity. It is a useful instrument for assessment of female incontinence and voiding symptom severity in clinical and research settings.

Pressure Flow Studies in Men and Women

There are well established pressure flow criteria and nomograms for urinary obstruction in men. The pressure flow criteria for female urinary obstruction are not well established due to differences in female voiding dynamics as compared to men. Typically, other information such as radiographic data and clinical symptoms are needed to facilitate the diagnosis. Detrusor underactivity remains a poorly studied clinical condition without definitive urodynamic diagnostic criteria. Modalities proposed for objective analysis of detrusor function such as power (watt) factor, linear passive urethral resistance relation and BCI nomogram were all developed to analyze male voiding dysfunction. Overall, further investigation is needed to establish acceptable urodynamic criteria for defining detrusor underactivity in women.

Detrusor Underactivity and Detrusor Hyperactivity with Impaired Contractility

Detrusor underactivity (DU) is a condition of impaired bladder contraction strength or duration resulting in impaired bladder emptying. In contrast, detrusor hyperactivity with impaired contractility (DHIC) is a condition in which patients paradoxically exhibit detrusor overactivity during storage yet are unable to mount a sufficient detrusor contraction during voiding to completely empty the bladder. Both conditions are often mistaken for bladder outlet obstruction. These conditions are more commonly seen in institutionalized elderly patients with either urinary retention or incontinence. To date, the exact etiologies of DU and DHIC remain unclear. Accurate diagnosis is based on clinical suspicion, complete history and physical exam, and videourodynamic evaluation. However, in certain patients, such as frail elderly patients, a full workup may not be warranted if it will not influence treatment decisions. Treatment of these disorders is primarily based on patient bother, with behavior modification first implemented, followed by pharmacotherapy with addition of CIC or indwelling catheter as indicated.

Dynamic Pelvic Magnetic Resonance Imaging Evaluation of Pelvic Organ Prolapse Compared to Physical Examination Findings

OBJECTIVE To compare dynamic magnetic resonance imaging (dMRI) defecography phase findings with physical examination (PE) grading in the evaluation of pelvic organ prolapse (POP). METHODS We retrospectively reviewed 274 consecutive patients who underwent dMRI with defecography. Baden-Walker grading of POP, absolute dMRI values, and grading by dMRI were collected for anterior, apical, and posterior compartments. Anatomically significant POP on PE was defined as Baden-Walker Grade ≥3 and on dMRI by dMRI Grade ≥2. A Spearmans Rank correlation was performed between absolute dMRI values and respective POP grades. RESULTS A total of 178 female patients were included. Anatomically insignificant and significant cystoceles had a 26.4% (19/72) and 84.6% (66/78) agreement respectively. Anatomically insignificant and significant apical prolapse had a 2.0% (2/100) and 62.9% (17/27) agreement respectively. Anatomically insignificant and significant posterior prolapse had a 49.5% (51/103) and 78.7% (59/75) agreement respectively. PE detected only 30% (9/30) of total dMRI detected enteroceles and misdiagnosed 10% (3/30) of these patients with a rectocele. CONCLUSION The dMRI defecography phase correlated well for anatomically significant prolapse in anterior and posterior compartments. dMRI was superior to PE for enterocele detection and was better able to distinguish an enterocele from a rectocele. Thus, dMRI may have the greatest diagnostic value in cases where the presence of an enterocele is unclear in apical and/or posterior compartments.

Sacral Neuromodulation for Overactive Bladder

Overactive bladder (OAB) is a urologic condition that negatively impacts quality of life. Sacral neuromodulation (SNM) is a safe and effective treatment option that has been studied extensively in patients with severe and refractory OAB. SNM significantly reduces urgency, frequency, and incontinence while also improving quality of life. Although SNM is not currently indicated for the treatment of OAB symptoms due to neurologic disease, recent literature suggests that these patients may also benefit from SNM. Other areas requiring further investigation include reduction of adverse events associated with SNM and the overall cost benefit ratio of SNM.

Improved Detection of Pelvic Organ Prolapse: Comparative Utility of Defecography Phase Sequence to Nondefecography Valsalva Maneuvers in Dynamic Pelvic Floor Magnetic Resonance Imaging

PURPOSE To evaluate the utility of a defecography phase (DP) sequence in dynamic pelvic floor MRI (DPMRI), in comparison to DPMRI utilizing only non-defecography Valsalva maneuvers (VM). MATERIALS AND METHODS Inclusion criteria identified 237 female patients with symptoms and/or physical exam findings of pelvic floor prolapse. All DPMRI exams were obtained following insertion of ultrasound gel into the rectum and vagina. Steady-state free-precession sequences in sagittal plane were acquired in the resting state, followed by dynamic cine acquisitions during VM and DP. In all phases, two experienced radiologists performed blinded review using the H-line, M-line, Organ prolapse (HMO) system. The presence of a rectocele, enterocele and inferior descent of the anorectal junction, bladder base, and vaginal vault were recorded in all patients using the pubococcygeal line as a fixed landmark. RESULTS DPMRI with DP detected significantly more number of patients than VM (p<0.0001) with vaginal prolapse (231/237, 97.5% vs. 177/237, 74.7%), anorectal prolapse (227/237, 95.8% vs. 197/237, 83.1%), cystocele (197/237, 83.1% vs. 108/237, 45.6%), and rectocele (154/237, 65% vs. 93/237, 39.2%). The median cycstocele (3.2cm vs. 1cm), vaginal prolapse (3cm vs. 1.5cm), anorectal prolapse (5.4cm vs. 4.2cm), H-line (8cm vs. 7.2cm) and M-line (5.3cm vs. 3.9cm) were significantly higher with DP than VM (p<0.0001). CONCLUSIONS Addition of DP to DPMRI demonstrates a greater degree of pelvic floor instability as compared to imaging performed during VM alone. Pelvic floor structures may show mild descent or appear normal during VM, with marked prolapse on subsequent DP images.