I ORAL PRESENTATIONS

Topic 4: Neurogenic Detrusor Overactivity
Chair: Ed McGuire, JJ Wyndaele

Introduction Lecture:
THE NEUROGENIC BLADDER, FACTORS DETERMINING OUTCOME AND THEIR
TREATMENT AT THIS MOMENT
Ed McGuire

Over the past 44 years, the life of this society, our concepts regarding neurogenic
vesical dysfunction related to spinal cord injury or disease, have evolved very
substantially. We have excellent evidence that control of bladder pressure is the
cornerstone of all our treatment. Most spinal treatment centers no longer use chronic
catheters for management of poor voiding or incontinence. Residual urine volumes are
no longer measured as an idex of successful treatment, and intermittent catheterization
is an acceptable long term method of treatment.Treatment of chronic bacteriuria
remains a problem, but not one that actually impacts outcome very much, except for
the emergence of multi-resistant strains of organisms which the next generation of
physicians will treat in a futile effort to cure an infection, just as is done today. The
simple truth is there are no significant urinary infections in this population which can be
treated by antibiotics alone, and most of those which occur in low pressure bladders do
not need to be treated.

How we control detrusor pressure and prevent or obviate the effects of a low
compliance bladder is now in a state of furious evolution. Early treatment was by
sphincterotomy, or vesicostomy.Both did reduce bladder pressure,but "failure" was
identified by persistent residual urine : not a usefull measurement in these cases.These
procedures fell out of favor and ileal loop diversion, ileovescostomy, augmentation
cystoplasty, replacement cystoplasty and cystectomy and continent diversion emerged
as effective treatments to reduce high bladder pressure or prevent it's develpment in
the first place.With the exception of ileal loop diversion, which has poor long term
outcomes , bladder enlargement procedures do effectivly, and permanently,lower
bladder pressures. But: these are complex procedures in relatively sick patients and
both short and long term morbidity are a real problem.

Hence in the last few years our efforts have focused on the correct goal: reducing
bladder pressure but by means other than an enterocystoplsty and other major intraabdominal
operations where bowel is used to create part or all of a urinary reservoir.

These include dorsal rhizotomy, dorsal root ganglionectomy , with and without anterior
sacral root stimulation, myectomy, Botox injections into the bladder and sphincter,
perpiheral electrical stimulation and more recently vibratory stimulation.

All of these techniques do indeed reduce bladder pressure and reverse, in some cases,
a low compliance bladder just as did sphincterotomy 20 years ago. It seems probably
that we will shortly have non or minimal invasive techiques to obviate the development
of the low compliance bladder and detrusor hyper- reflexia. Perhaps one day we will
understand the subcellular processes which underpin the effect of neurogenic
dysfunction on the bladder so that we can control it at it's source.

13/4 Clinical Usefulness of Urodynamic Assessment for Maintenance of
Bladder Function and Prevention of Renal Damage in Patients with Spinal Cord Injury

J. Pannek, M. Nosseir, and A. Hinkel
Department of Urology and Neuro-Urology, Ruhr-Universität Bochum, Marienhospital
Herne, Widumer Strasse 8, 44627 Herne, Germany

Detrusor hyperreflexia with elevated storage pressure presents a major risk factor for
renal damage in spinal cord injury patients. We evaluated the long term results of 80
spinal cord injury patients (60 male, 20 female; mean age 29.6 years) treated at our
institution.

Mean follow-up was 67.3 months (range 60-103 months). At initial presentation, 51
patients performed intermittent catheterization, 7 had indwelling catheters, 10 utilized
reflex voiding, 2 patients presented with a Brindley stimulator, and 10 patients used
abdominal straining. At the end of our study, no patient had signs of renal damage. To
achieve that goal, 8 patients underwent sphincterotomy, 3 received a Brindley
stimulator, 3 underwent bladder augmentation, a Kock pouch was performed in one
patient, and 12 patients were treated with botulinum-A-toxin injections in the detrusor
muscle. 22 patients received intravesical anticholinergic therapy. In merely 3 patients,
treatment was not modified during the entire follow-up.

In the long term, treatment strategy of neurogenic bladder dysfunction in patients with
spinal cord injury had to be modified in almost all patients. 18.8% underwent surgery.
For protection of the upper urinary tract, a regular urodynamic follow up is mandatory.

14/4 Efficacy and Safety of Propiverine in Comparison to Oxybutynin in
Children with Neurogenic Detrusor Overactivity (Ndo) – An Observational Cohort Study

H. Madersbacher1, G. Mürtz2, S. Alloussi3, M. Beuke4, M. Bürst5, B. Domurath6,
T. Henne7, I. Körner8, A. Niedeggen9, J. Nounla10, J. Pannek11, M. Schuldt12, H.
Schulte-Baukloh13, D. Schultz-Lampel14, S. Siemer15, T. Stuckert16, B. Willer14,
P. Bock17, J. Hanisch17

15 referral centers for children suffering from neurogenic detrusor overactivity:
Austria: 1) Innsbruck; Germany: 2) Dresden 3) Neunkirchen 4) Hamburg-
Harburg 5) Deggendorf 6) Bad Wildungen 7) Hamburg-Altona 8) Essen 9) Berlin
10) Leipzig 11) Herne 12) Greifwald 13) Berlin 14) Villingen-Schwenningen 15)
Homburg/Saar 16) Zwickau; Switzerland: 17) Basel, Schweiz

Introduction: Assessment of efficacy and safety of propiverine (Mictonetten_) and
oxybutynin in children with NDO aged 1–18 years.

Materials: In a comparative muticenter (14) cohort study 255 children with NDO (199
myelomeningocele (MMC), 46 spinal cord injury) were treated with anticholinergics for
2.5 years on average and were evaluated retrospectively (propiverine 127, oxybutynin
128). Mean age at treatment initiation was 7.18 (propiverine) and 7.98 (oxybutynin)
years.

Results: Efficacy outcome maximal detrusor pressure at micturition was on average
significantly reduced (propiverine pre 59.3, post 36.7; oxybutynin pre 65.2, post 55 cm
H20). Clinically relevant reductions of detrusor pressure (below 40 cm H20 or reduction
by >50%) resulted in 74% compared to 50% (propiverine versus oxybutynin),
corresponding to other urodynamic and clinical outcomes. Propiverine and oxybutynin
demonstrated an improvement of reflux, especially in those with more severe gradings
(stage III-V): In both treatment groups 26 cases were affected prior to treatment
compared to 9 cases post treatment.

Propiverine was better tolerated than oxybutynin (9.40 vs. 17.46% adverse events
overall), in children with MMC significantly better.

Conclusions: This study demonstrates a more effective reduction of maximal detrusor
pressure at micturition and a better tolerability of propiverine compared to oxybutynin.

15/4 Reductions in neurogenic urinary incontinence after treatment with
botulinum toxin A (BOTOX®): impact of patient demographics

B. Schurch, M. de Sèze, P. Denys, E. Chartier-Kastler, F. Haab, K. Everaert, P.
Plante, B. Perrouin-Verbe
University Hospital Balgrist, Zurich, Switzerland

Introduction: Urinary incontinence (UI) is a common consequence of spinal cord injury
and can reduce patients’ quality of life. Recent data suggest BOTOX® may be an
effective treatment for UI, but it is important to understand how different patient
populations respond. This study compared two doses of BOTOX® in the treatment of
neurogenic UI, and investigated how patient demographics influence response.

Methods: 59 patients with neurogenic UI resulting from either spinal injury (53
patients) or multiple sclerosis (6 patients), poorly managed by anticholinergics, were
recruited into this double-blind multi-centre trial. Patients were randomised to receive a
single dose of either BOTOX® (200 U or 300 U) or placebo, administered to the
detrusor as 30 injections, each of 1 ml. Effects on UI were monitored for 24 weeks.

Results: BOTOX®, but not placebo, produced statistically significant reductions from
baseline in daily UI episodes by 2 weeks (p_0.05). The improvement was comparable
for men and women, for younger (<30 years) and older (30-60 years) patients, and for
patients with spinal cord injury compared to the full study population.

Conclusions: BOTOX® significantly improved incontinence frequency in patients with
neurogenic UI. Patient response to treatment was not affected by gender, age or
neurological trauma.

16/4 7 years Botulinum-A-Toxin on Detrusor Overactivity

M. Stöhrer, A. Wolff, G. Kramer, D. Leuth, R. Steiner, D. Löchner-Ernst
Urolog. Abt. Berufsgenossenschaftliche Unfallklinik Murnau, Germany

For many years Botulinum-A-Toxin is not only known as one of the strongest toxins,
but also as an outstanding medication to suppress chronical muscle spasm. For this
reason it has been used in neurology by cross striped muscular system in this special
field and is also efficiently used in the plastic-surgical area.

Some years ago tests on animals demonstrated that it also has an effect on smooth
muscles. Therefore we startet 1998 to inject Botulinum-A-Toxin into the detrusor
muscle to accomplish a paralysis of the muscle on patients with neurogenic detrusor
overactivitiy. The indication was made on patients with an aggressive detrusor function,
which could’nt be treated sufficiently with anticholinergic substances, or the side effects
would’nt allow a higher dosage.

This way the patients were spared further surgical interventions (enterocystoplasty,
deafferentation) etc.

Patients and methods:
In our hospital in Murnau 277 patients, most of them with traumatic spinal cord injury,
also spina bifida, MMC and multiple sclerosis, were treated with alltogether 481
injections until the end of Febuary 2005.

There were 300 units Botox on adult patients (children 100 – 200 units) or 500 – 1000
units Dysport on several areas injected, whereby the area of the trigonum could be
bypassed, especially the one closed to the ostien.

Results:
In 95% of the patients the succes was remarkable. After about 1-2 weeks in almost all
cases a mostly complete immobilisation of the detrusor could be reached. Post
operative the compliance was in a normal range. Bladder capacity could be raised to a
physiological level. Unrestraint acitvities could’nt be established in the responders (~ ~
95%). After the effectivity startet (8-14 days), especially female patients called
spontaneously to report, that for the first time since there disfunction of their bladder
they stayed completely dry.

The effect stayed on the average for 10 months (3-14 months). The anticholinerge
therapie could be partly dismissed or considerable reduced.

After the first year of experience on adults, we started to use this medication on
children and youth, the dose according to their weight, with same results.
There were hardly any side effects under the dose we prefer to use. In three cases
there could have been discussed a slight weakening of the striated muscle. In three
non-responders antibodies were found.

Conclusions:
Considering the presented results with Botulinum-A-Toxin on detrusor overactivity,
there is a considerable enrichment of our therapeutical possibilities, which is located
between the treatment with medication and bigger interventions, for extension,
augmentation or replacement of the bladder. At the present this indication is „of label
use“ in most countries. Appropriate studies are in progress.

17/4 Efficacy and tolerability of propiverine compared to oxybutynin in
neurogenic detrusor overactivity

Stöhrer Manfred1, Mürtz Gerd2, Schnabel Frieder2, Kramer Guus1, Kirch
Wilhelm3 and the Investigator Group
1BG-Unfall-Klinik, Murnau, Germany. 2Apogepha, Dresden, Germany. 3University
of Technology, Dresden, Germany, altogether 20 study centers.

Aims of Study
Comparison of efficacy and tolerability of propiverine and oxybutynin in neurogenic
detrusor overactivity (NDO).

Methods
In this randomised, double-blind, multicenter (20) study 131 patients were recruited.
Inclusion criteria: NDO, maximum cystometric capacity beyond 300 ml. Outcome
parameters were assessed before (V1) and after (V2) 21 days of propiverine (15 mg
t.i.d.) or oxybutynin (5 mg t.i.d.) treatment.

Results
Efficacy–Cystometry: Maximum cystometric capacity increased significantly in the
propiverine (V1: 198±110, V2: 309±166) and the oxybutynin group (V1: 164±64, V2:
298±125). Maximum detrusor pressure during filling phase decreased significantly in
the propiverine (V1: 57±36, V2: 38±31) and oxybutynin group (V1: 69±35, V2: 43±29).
No significant differences in these parameters resulted between both groups.
Efficacy–Bladder Diary: Micturition frequency/24h and incontinence episodes
decreased in both groups to a comparable extent.

Tolerability: 63% of patients treated with propiverine presented with anticholinergic
adverse events compared to 78% treated with oxybutynin. Dryness of the mouth was
reported significantly more often in the oxybutynin (67%) compared to the propiverine
group (47%).

Conclusions
Propiverine and oxybutynin are equieffective in the treatment of NDO. A trend for
superior tolerability of propiverine compared to oxybutynin exists.

18/4 Suppression of Neurogenic Detrusor Overactivity in Spinal Cord
Injured Patients by Conditional Electrical Stimulation

J. Hansen, S. Media, M. Nøhr, F. Biering-Sørensen, T. Sinkjær and N.J.M.
Rijkhoff
Center for Sensory-Motor Interaction (SMI), Department of Health Science and
Technology, Aalborg University, Denmark

Purpose: Suppression of neurogenic detrusor overactivity (NDO) by automatic event
driven electrical stimulation of the dorsal penile/clitoral nerve was evaluated in
individuals with spinal cord injury (SCI).

Methods: The study included 16 SCI patients, 2 females and 14 males, with NDO,
bladder capacity below 500 ml, age over 18 years and complete or incomplete
suprasacral SCI. Detrusor pressure (Pdet) was recorded during an ordinary natural
bladder filling. In a similar subsequent recording Pdet triggered electrical stimulation
when the pressure exceeded 10 cmH2O.

Results: Of the 16 patients enrolled in this study 13 had an increased bladder capacity
together with a storage pressure decrease as a result of automatic event driven
electrical stimulation. In two patients stimulation could not inhibit the first undesired
contraction and one patient could not tolerate the stimulation. During the stimulated
filling Pdet never exceeded 55 cmH2O and the storage pressure is thus sufficiently low
to prevent kidney damage. An average increase in bladder capacity of 53% was
obtained.

Conclusion: This study demonstrates the feasibility of automatic event driven
electrical stimulation in the treatment of NDO. Although our experimental setup is not
suitable in a clinical setting, the treatment modality is promising and it warrants further
investigation.

More Abstracts >
< Back to Index