Control of Bladder Function - the Overactive Bladder

Wednesday, 17 June 1998

The overactive bladder is a disease with a high prevalence and can cause a lot of discomfort. The International Continence Society (ICS) introduced a classification for the overactive bladder, but it remains questionable whether the difference between idiopathic, myogenic and neurogenic causes can easily be made from a diagnostic standpoint.
The knowledge on the discomfort of the disease is poorly understood.
The symposium will deal with these problems and address topics like the central control of micturition, epidemiological aspects of the overactive bladder and therapeutic options, with emphasis on the treatment results of the new muscarinic inhibitor.

SCIENTIFIC PROGRAM
12.00	Registration and coffee
12.30	Lunch
13.15	Opening of symposium	K.H. Kurth
13.20	The Central Control of Micturition and Continence of Humans	B.F. Blok
13.40	Selective Pharmacological Manipulation of the Smooth Muscle Tissue of the GU-tract	C. Stief
14.05	Epidemiology of Urinary Incontinence	C. Hampel
14.25	Idiopathic, Neurogenic and Myogenic Overactive Bladder	J.L.H.R. Bosch
14.50	Break
15.10	Urinary Potassium and the Overactive Bladder	G. Hohlburgger
15.30	Treatment of the Overactive Bladder	E.J. Messelink
16.00	Willingness to Pay for Reduced Incontinence Problems	P.Abrams
16.25	Detrusor Activity Index: Quantification of Detrusor Overactivity by Ambulatory Monitoring	E. van Waalwijk van Doorn
16.45	Treatment Algorithm of the Overactive Bladder	Ph.E.V.A. van Kerrebroeck
17.10	Summary of the Symposium	K.H. Kurth
17.30	Drinks and Snacks
19.30	Appetizer and Dinner

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From twelve o'clock the participants trickled in, although for some the midweek afternoon proved to be more difficult to barter for some time off from patients and other staff. Since the holiday period was coming closer, the roads were being taken care of to make sure that - as is customary in the Netherlands - most roads are broken up by the time the road workers are all going off to some far away foreign country to enjoy a well earned vacation. So it took your reporter some extra time to pass vast stretches of speedway at turtle speed where either road works were under way or just off limits because they were planning some works which they were certain they could not possibly finish before holiday time.
The 'Landgoed Lauswolt' is located the middle of Fryslân, the Frisian country, in the north of the Netherlands. In the midst of the green countryside near a little village the large estate is located far away from the busy parts of the Netherlands in the west, also known simply as 'Holland'. Friesland (Fryslân) has its own language, although some call it a dialect. Fortunately, the waiters all spoke fluent dutch and were able to serve us a welcomed lunch, although Paul Abrams seemed to have second thoughts about the milk served with it. Philip van Kerrebroeck was heard to say that he had also welcomed the invitation to talk about the overactive bladder, but was not informed until much later that the location of the symposium was about 350 km from his beloved Maastricht, at the other - southern - end of the Netherlands in Limburg, where they tend to speak an entirely different dialect.

Dr Blok (Groningen, Netherlands), a neurologist, told us about the controls of micturition in cats and humans. He thanked Pfizer for inviting him to this symposium, but then was reminded by Kurth that is was not Pfizer after all; fortunately, today's presentation was obviously not much different from the one he much have prepared for the wrong company. It seemed that those species are much alike as far as voiding is concerned. In great detail, dr Blok showed us diagrams on neurological bundles, that went back to our early medical training. Some among us woke up at this revival of memories, while others took their chance to examine their inner selves after a recent lunch. Using SPECT scans, it is now possible to examine the state of the brain right at the moment of micturition and thus show where the important micturition centers in the cerebrum and pons are located, although much is still unknown and - as ever - more studies are necessary to fully appreciate the whole of the cerebral micturition control. It seems clear, however, that there is a lot of supraspinal regulation going on to control voiding in both cats and humans. Some of this pontine and cerebral regulation explains inconsistencies, like the fact that there is no relaxation of the pelvic floor in paraplegics.

Dr Stief (Hannover, Germany) summarized the possible pharmacologic mechanisms that may play a role in the manipulation of the smooth muscle tissues of the urinary tract. Serotonin and dopamin were shown to have no effect on the overactive bladder. Concerning the peripheral influences, the effect on the cell membrane, especially the potassium-, calcium- and chloride-ion channels may prove to be a future foothold in influencing the smooth muscle cell activity. Today, more is to be expected of pharmacological intervention of intracellular processes. Simply put, a (slight) rise in intracellular Calcium-ion content will cause smooth muscle cell relaxation. The amount of intracellular 'free Calcium' is determined by cAMP and cGMP as so called 'second messengers'. A rise in these second messengers will cause a rise in free Calcium. The enzyme phosphodiesterase (PDE) breaks down cAMP and cGMP, so an inhibitor of this enzyme would prevent this and thus promote smooth muscle cell relaxation. There are about 8 families and 40 sub-families of PDE's. In the bladder, type 1 to 5 are found, but only type 1 is functioning. Using a type 1 PDE inhibitor, which has been on the market in Japan for over 30 years for another indication (but even the producing company knew it didn't work) Stief et al. showed a significant relaxing effect of bladder muscle in humans. Sildenafil (Viagra), however, a type 5/6 PDE inhibitor, will unfortunately have no side-effect as bladder relaxant.

Dr Bosch (Rotterdam, Netherlands) brought forward his views on a classification of the unstable bladder. He divided the causes into those attributable to the micturition reflex, to neurotransmitters, the myogenic type and behavioral causes. He showed very nicely that the level of the defect in the micturition reflex could very well predict the effect on micturition and the urodynamic findings. Changes in the neurotransmitters could be categorized into changes in the type of transmission, the number of transmitters and the detrusor response. In the myogenic type he mentioned a synchronization of spontaneous activity as a possible cause of instability. He observed an increase in flow rate due to a decrease in detrusor instability as a side-effect in electrostimulation for bladder overactivity. As always, the slide projection continues to be an almost unsurmountable problem.

Then it was time for a break, which was cut short by dr Kurth, who limited our time off to five minutes due to the lengthy presentations/discussions.

Our Austrian colleague, dr Hohlburgger (Innsbruck), then tried to take us back into the bladder again by referring to the effect of urinary potassium on the urothelium and the blood flow in the bladder wall. The presentation again started off with slide trouble, but some unspoken blasphemy finally did the trick. Aided by his nice, but sometimes cloudy Austrian accent, his explanation of the flux of Potassium in- and outside the urothelial cell went too far for most of us. The large number of excellent slides resembled a piece of modern art, but unfortunately passed too quickly to fully understand their significance. To prove his point, dr Hohlburgger mentioned that he was able to get more out of the urodynamic investigation by using KCl instead of NaCl to fill the bladder. In that way, he saw more cases of instability; which is not surprising, when you think about it.

Paul Abrams (Bristol, UK) talked about the instruments needed to get more information on the extent of the problem of the overactive bladder and its impact on society. Of all patients with incontinence, only fifty percent press for treatment. The so called bothersomeness of the problem is not easily measured. The available generic instruments are not specific enough to give us a good idea, while the more specific ones are too recent to be validated properly. He also mentioned the recent 'Willingness to Pay' studies done in Sweden and the US, which were also dealt with at a recent Pharmacia meeting during the AUA in San Diego. It turned out that Swedes were willing to pay twice as much for twice as much results, which is not surprising, and that the amount they were willing to pay for 25% reduction of symptoms was 500 Swedish Kronar. The American people were even willing to pay exponentially more for a twice higher effect. There is still much work to be done, but Paul was already heading back to catch his flight to Bristol.

Ernst van Waalwijk van Doorn (Maastricht, Netherlands), a physicist who is considerably shorter than his name, went forth with a nice computer-animated presentation on the use of Ambulatory Urodynamic Investigation (AUI) and the Detrusor Activity Index (DAI), developed in Maastricht. It seemed that the DAI was able to discern between true, urodynamic, overactive bladder and the non-overactive one, although there was still a large grey area left. The AUI is an important tool in the investigation.In 25% of normal individuals unstable bladder contractions occur in everyday life.

Bert Messelink (Amsterdam, Netherlands) took us on a ride in therapy land. He stressed the fact that exercises tor train the pelvic floor should include a training in the coordination of these muscles as well, a pelvic floor re-education so to say, in which biofeedback may be used to speed up the process. Just 'bladder exercises does lead to cure in 15% and improvement in another 50%, but real pelvic floor training with the help of a specialized physiotherapist has far better results.

Finally, Philip van Kerrebroeck spoke about a treatment algorithm of the overactive bladder, which, unfortunately, does not exist. Too many questions on definition, diagnosis and treatment outcomes remain, so creating a viable algorithm is still impossible. He did stress that one should always be aware of known causes like bladder outlet obstruction or stress incontinence, which can and need to be treated before any other therapy for the overactive bladder is started. In case of pharmacological treatment, one should await at least six weeks of therapy before failure (or success) can be declared. This period also takes psychological and placebo effects into account.

Dr Kurth then decided it was enough and started to close the meeting, but then instinct took over and made him proceed in summarizing what was said today.