Neurourology, Diet, and Painful Bladder

Meeting Review

RIU0383_03-14.qxd 3/15/08 3:03 AM Page 70 MEETING REVIEW Neurourology, Diet, and Painful Bladder Highlights of the 37th Annual Conference of the International Continence Society, August 20-24, 2007, Rotterdam, Netherlands [Rev Urol. 2008;10(1):70-72] © 2008 MedReviews, LLC Key words: Overactive bladder • Painful bladder syndrome • Sensory nerve testing • Interstitial cystitis • Diet • Comorbidities successful 2007 annual conference of the International Continence Society (ICS) was held at the Rotterdam Concert and Congress Centre in the Netherlands. The meeting was hosted by Professor Ruud Bosch, and over 2500 delegates came from 69 countries. They represented many disciplines including urologists, urogynecologists, internists, gastroenterologists, geriatricians, A Reviewed by Hann-Chorng Kuo, MD, Department of Urology, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan; Yao-Chi Chuang, MD, Division of Urology, Chang Gung Memorial Hospital Kaohsiung, Chang Gung University, Taiwan; and Michael B. Chancellor, MD, Director of Neurourology and Female Urology, University of Pittsburgh Medical Center, Pittsburgh, PA. 70 VOL. 10 NO. 1 2008 neuroscientists, nurses, continence advisors, and physiotherapists, all of whom are involved in research, treatment, and care of people suffering from incontinence and pelvic-floor disorders. One key theme of the meeting was painful bladder syndrome/ interstitial cystitis (PBS/IC), so we will review a few presentations and workshops on this topic held at the ICS. Neurological Factors Our friend Professor Osamu Ukimura and associates at the urology department at Kyoto Prefectural University presented their expanding experience with selective bladder sensory nerve testing.1 There is increasing interest in quantitation of bladder sensory nerve function and the Neurometer® (Neuroron, Baltimore, MD) is an electrodiagnostic device that measures REVIEWS IN UROLOGY the current perception threshold (CPT) on small myelinated (A-delta) and unmyelinated (C) afferent nerve fibers. Ukimura and associates have previously described the first application of this device for quantitative neuroselective measurement of the CPT (ie, vesical sensory threshold) values of the A-delta and C fibers in the human bladder mucosa, allowing the detection of hyperesthetic (abnormally low) or hypoesthetic (abnormally high) vesical sensory threshold. Diagnosing the quantitative dysfunction on such specific subpopulations of bladder afferent fibers in patients with overactive bladder (OAB) or PBS/IC could improve understanding of pathogenesis in the individual patient, potentially guiding appropriate therapeutic intervention for each patient. RIU0383_03-14.qxd 3/15/08 3:03 AM Page 71 Neurourology, Diet, and Painful Bladder The study analyzed the relationship between the CPT values of the bladder afferent fibers and the clinical characteristics of patients with OAB and PBS/IC in whom previous therapeutic interventions were ineffective. Thirtyeight selected patients (8 male, 30 female) with OAB (n  25) and PBS/IC (n  13) were enrolled. The CPT values (1  0.01 mA) were measured at frequencies including 250 Hz and 5 Hz by Neurometer using an intravesical electrophysiology catheter (6 Fr in diameter) on the posterior bladder body wall and skin dispersion electrode. Continuous sinusoidal stimuli at frequencies of 250 Hz and 5 Hz reflect functions of the small myelinated (A-delta) and the unmyelinated (C) fibers, respectively. Bladder diary was reported in all patients. In the patients with PBS/IC, the Interstitial Cystitis Symptom Score (O’Leary-Sant symptom index) was reported. Cystoscopically, the glomerulation was found in 9 out of the 13 PBS/IC patients. In the patients with refractory PBS/IC, significant linear correlations were found between the morbidity time and the bladder CPT value of A-delta fiber (r  0.83, P  .002) as well as C-fiber (r  0.61, P  .049). In patients with refractory OAB, significant linear correlation was found between the morbidity time and the bladder CPT value of C-fiber (r  0.47, P  .031), but not of A-delta fiber (r  .26, P  .2). The overall mean CPT value of C-fiber was significantly lower (P  .040) in the patients with refractory OAB (mean, 31.9; range from 2.4 to 173) than in the patients with refractory PBS (mean, 61.6; range from 3.5 to 173). The overall mean CPT values of A-delta fiber were similar between the patients with refractory OAB (mean, 85.2; range from 5 to 220) and with refractory PBS/IC (mean, 82.3; range from 5.9 to 216). Among the reported symptoms, in the patients with refractory PBS/IC, the bladder CPT value of C-fiber had significant linear correlation to the severity in 24-hour frequency (r  0.65, P  .03) as well as in maximum voided volume (r  0.67, P  .02), although no clear correlation between the CPT values and the patient-reported symptoms was found in the patients with refractory OAB. In the patients with refractory PBS/IC, the cystoscopic finding of the glomerulations was associated with the higher CPT values of C-fiber (P  .031) and A-delta fibers (P  .073). The measurement of neuroselective CPT values could identify dysfunction of the subpopulations of bladder sensory afferent fibers associated with the clinical characteristics. The CPT values of the 250 Hz (A-delta fiber) and 5 Hz (C fiber) in the patients with either refractory OAB or PBS/IC were found to become higher according to the prolonged morbidity time. Patientreported symptoms such as the 24hour frequency and maximum voided volume had greater correlation with CPT values of C-fiber in the patients with refractory PBS/IC than in patients with refractory OAB. These results suggested possible differences in neuropathogenesis between refractory OAB and PBS/IC. The neuroselective quantitative measurement of CPT value of the bladder afferent fibers in the patients with OAB and PBS/IC may improve patient care by allowing disease selective therapy and improve understanding of neuropathogenesis in the individual patients with OAB and PBS/IC. Another friend, Dr. Larissa Rodriguez at the University of California, Los Angeles, and her team presented an excellent study that received rave reviews. Twiss and colleagues2 noted that the driving factor for their research was the fact that PBS/IC appears to have significant central and neuropathic components, as well as involvement of central modulatory pathways including those involving the limbic system. The startle blink reflex (SBR) is a defensive, involuntary eye-blink in response to sudden intense stimuli. This reflex is modulated by the amygdala, a component of the limbic system involved in modulation of emotional states and physical sensations. Increases in SBR magnitude represent an objective index of affective response to stimuli, such as threat of pain. To test the hypothesis that PBS/IC patients have an upregulation of central pain modulation pathways, the authors compared the SBRs of healthy controls with that of PBS/IC patients. The SBRs were examined for 6 PBS/IC women and 19 healthy women under threat and safe periods. During threat periods, subjects would possibly receive aversive electrical stimulation to their bladder region. Each threat period consisted of an early and late phase. If stimulation were to occur, it would do so during the late phase. No stimulation was given during safe periods. SBRs were measured during all phases. Mixed-effects analysis for repeated measures was applied to determine the influence of diagnosis (PBS/IC, Control), threat (Danger, Safe), and phase (Early, Late) on the squareroot transformed SBRs. The results of the study showed that PBS/IC patients have significantly greater SBRs than controls during baseline and during the non-imminent threat periods of the study. A similar alteration of the startle reflex is observed in humans with anxiety disorders and posttraumatic stress disorder. This is objective evidence that PBS/IC patients may have upregulation of limbic responses involved in anxiety and stress leading to altered pain perception and abnormal modulation of afferent pain signals. The authors’ data strongly suggest that central alteration of pain perception may be involved in the PBS/IC disease process. VOL. 10 NO. 1 2008 REVIEWS IN UROLOGY 71 RIU0383_03-14.qxd 3/15/08 3:03 AM Page 72 Neurourology, Diet, and Painful Bladder continued Workshops on Diet and Diagnosis We also attended two workshops on PBS/IC. One interesting and unique session focused on diet and PBS/IC: Many patients will know from their own experience that certain foods and beverages appear to exacerbate their bladder symptoms. Although there has until recently been little research into this aspect, long lists of potential irritants have been compiled on websites and may be very alarming to a newly diagnosed patient. Every patient is different, but by eliminating items known to cause irritation based on their own experience, a patient can at least avoid unnecessary exacerbation of the symptoms without becoming paranoid about diet. Patients with milder PBS/IC may even find that diet modification is the only treatment they need. This study3 on the effects of food and drink was published in July 2007. It was based on a questionnaire distributed to a group of 104 PBS/IC patients. The aim was to see whether certain foods, beverages, and diet supplements affected PBS/IC symptoms either positively or negatively. One-hundred-seventy-five food items were studied. It was concluded that there are, indeed, a large number of PBS/IC patients whose symptoms Table 1 Foods Best Avoided by Most Painful Bladder Syndrome/ Interstitial Cystitis Patients • Food/drink containing caffeine • Other acidic food: tomatoes, vinegar, etc. • Certain artificial sweeteners • Alcoholic drinks • Carbonated drinks/soda • Highly spiced food especially with hot pepper 72 VOL. 10 NO. 1 2008 are exacerbated by consumption of specific items. The study identified the most bothersome foods as: items containing caffeine, citrus fruits and juices, tomatoes and tomato products, items containing vinegar, spicy food, alcohol, and certain artificial sweeteners (Table 1). Coffee was found to be the most bothersome. The authors suggest, however, that the effect of caffeine may be related to its diuretic effect, resulting in increased bladder filling. The study indicated that exacerbation appears to be worse with foods that contain hot pepper (eg, Indian, Mexican, and Thai food) suggesting that some component of hot peppers may be causing this exacerbation of symptoms, and that this might be capsaicin. Patients in the study varied greatly regarding the effects of fruits and juices. Analysis of the results suggested a role played by citrate in aggravating symptoms. As far as is known, the mechanism of acidic food on bladder symptoms has not yet been studied. Some patients are known to experience relief through taking alkalizing agents such as calcium glycerophosphate or bicarbonate of soda. There was no correlation shown in this study between having allergies and reporting that food items exacerbated symptoms. Another workshop4 chaired by Professor Jørgen Nordling, MD, with presentations by urologists Ralph Peeker, MD, and Arndt van Ophoven, MD, and internist-immunologist Joop van de Merwe, MD, presented standard diagnostic procedures and a standard list of confusable diseases that produce similar symptoms and consequently need to be excluded, as proposed by the European Society for the Study of IC/PBS (ESSIC), together with an innovative patient subclassification system based on diagnostic procedures carried out and cystoscopic and morphological REVIEWS IN UROLOGY findings. It is planned to put this system to the practical test in research in the coming years. Also presented were diet and self-help, medical, and surgical treatment of PBS/IC. This workshop included a presentation on PBS/IC and associated disorders. Many diseases have been shown to have a higher prevalence in patients with PBS/IC. According to Dr. van de Merwe, awareness of associated diseases for PBS/IC is important, not for the diagnosis of PBS/IC but for the patient. For optimal treatment of the “complete” patient, associated diseases should be diagnosed and treated by the right specialists. Treating the whole problem may require splitting the problem into separate elements to be handled by different specialists working as a team. Finally, COB Foundation offers a new and very moving DVD on Living with Interstitial Cystitis from the Cystitis and Overactive Bladder Foundation in the United Kingdom. If anyone would like a copy, please contact the COB Foundation: info@cobfoundation.org. References 1. 2. 3. 4. Ukimura O, Honjo H, Ushijima S, et al. Indication of neuro-selective pathogenesis in individual patients with overactive bladder or painful bladder syndrome by measure of current perception threshold of the bladder afferent fibers (abstract 84). Neurourol Urodyn. http://www .icsoffice.org/ALLAbstractWebSearch/index.asp? YEAR=2007. Accessed January 10, 2008. Twiss C, Kilpatrick L, Triaca V, et al. Evidence for central hyperexitability in patients with interstitial cystitis (abstract 9). Neurourol Urodyn. http://www.icsoffice.org/ALLAbstractWebSearch/ index.asp?YEAR=2007. Accessed January 10, 2008. Shorter B, Lesser M, Moldwin RM, Kushner L. Effect of comestibles on symptoms of interstitial cystitis. J Urol. 2007;178(1):145-152. Nordling J, van de Merwe JP, van Ophoven A, Peeker R. Workshop 20: Painful bladder syndrome. Workshop presented at: 37th Annual Conference of the International Continence Society; August 20-24, 2007; Rotterdam, Netherlands. http://webcasts.prous.com/ics2007/ WorkShops.asp?SID=12,13. Accessed January10, 2008.