Eur Urol Suppl 2007;6(2):245

889
INTRAVESICAL ADMINISTRATION OF BOTULINUM A TOXIN IN
SPINAL CORD INJURED PATIENTS: SUBUROTHELIAL VERSUS
INTRADETRUSORIAL INJECTIONS
Santaniello F., Proietti S., Zucchi A., Costantini E., Vianello A., Porena M., Giannantoni A.
University of Perugia, Department of Urology and Andrology, Perugia, Italy
Introduction & Objectives: Botulinum A toxin (BoNT/A) injections into the detrusor muscle have
been reported to provide satisfactory results in 60 to 100% of patients with neurogenic and non
neurogenic detrusor overactivity. Recent experimental and clinical observations showed that
BoNT/A can act at the level of the C fbers in the suburothelial space, thus modulating directly the
aferent arc of the micturition refex. We evaluated the efcacy and safety of BoNT/A suburothelial
injections and intradetrusorial administration, comparing clinical and urodynamic efects over
short-term follow up, in a group of spinal cord injured patients (SCI) with refractory NDO.
Material & Methods: After a baseline evaluation including history, voiding diary and urodynamics,
25 patients were selected and randomized into two groups. Patients in group 1 (13) received
suburothelial injections of BoNT/A 300 U diluted in 30 ml of normal saline, and patients in group
2 (12) received BoNT/A intradetrusorial injections, at the same dosage and dilution. BoNT/A was
administered in 30 sites in the trigone, posterior and lateral walls of the bladder, and the procedure
was performed in all cases under general anaesthesia. Clinical and urodynamic evaluations were
repeated at 1 and 3 mos follow up.
Results: Group 1. At 1 and 3 mos follow up, mean catheterizations and incontinence episodes were
signifcantly reduced compared to baseline (p<0.05 and p<0.01, respectively). On urodynamics,
we detected a signifcant increase in the frst volume of uninhibited detrusor contractions (from
242.4 98.7 to 354.6 59.7 ml, p<0.001) and in maximum cystometric capacity (from 279. 8
69 to 358.4 45.1 ml, p<0.01). We observed a signifcant reduction in maximum pressure
of uninhibited detrusor contractions. Group 2. A signifcant amelioration was observed in mean
catheterizations and incontinent episodes, at the same time-points. The frst volume of uninhibited
detrusor contractions and maximum cystometric capacity signifcantly increased (from 214.6
55 to 323.8 49 ml, p<0.001, and from 290.4 72 to 370.8 50 ml, p<0.01, respectively).
A signifcant reduction in maximum pressure of uninhibited detrusor contractions was detected.
Suburothelial versus intradetrusorial injections: we could not detect any signifcant diference
neither in clinical nor in urodynamics results between the two groups, at 1 and 3 mos follow up.
No side efects were observed during or after both treatment modalities.
Conclusions: In SCI patients afected by NDO, BoNT/A suburothelial injections are as efective
and safe as intradetrusorial injections, in a short term follow up. This confrms the hypothesis
that BoNT/A modulates the micturition refex by acting at the level of the aferent C fbers
into the bladder wall. Administering BoNT/A by suburothelial injections it is possible to avoid
neuromuscolar junction blocking, and this may be crucial in patients with NNDO who want to void
their bladder spontaneously.


890
BOTULINUM TOXIN-A (BTA) IN THE TREATMENT OF NEUROGENIC
DETRUSOR OVERACTIVITY INCONTINENCE (NDOI) - A
PROSPECTIVE RANDOMIZED STUDY TO COMPARE 30 VS. 10
INJECTION SITES
Karsenty G.
1
, Carsenac A.
1
, Boy S.
2
, Reitz A.
2
, Bardot P.
1
, Tournebise H.
1
, Bladou F.
1
, Serment G.
1
,
Schurch B.
2
1
Salvator Hospital, AP-HM, Medicine Faculty, University of Mediterrane, Urology, Marseille, France,
2
Balgrist
University Hospital - Paraplegic Research Center -Zurich University, Neuro-Urology, Zurich, Switzerland
Introduction & Objectives: Injection of 300 units of BTA into the bladder wall has been demonstrated to be a
safe and efective treatment of NDOI. The initial injection technique consists of 3O injection spots disseminated
over the detrusor muscle sparing the trigone. Spreading of biologic activity of BTA from a point injection has
been shown to be dose dependent in the animal striated muscle but has never been studied in the smooth
muscle. In this study the difusion of the biologic efect of BTA into human bladder wall was estimated by
decreasing the number of injection sites from 30 to 10.
Material & Methods: A prospective, randomized, single blinded study was conducted in adult patients with
chronic spinal cord lesion, sufering from refractory NDOI. Efcacy of two protocols injections of 300 units
of BTA (Botox) was compared. P1: 300 units over 30 points (10 units in1ml of saline/point) P2 same total
dose over 10 points (30 units in 1ml of saline/point). Trigone was spared. Patients were evaluated before
injection and 6, 12, 24, 36 weeks after. Hypothesis was equivalence between 30 and 10 injections in terms
of improvement of cystomanometric bladder capacity (CBC). Decrease of incontinence episodes (NID),
improvement of quality of life (Qualiveen), and pain at the procedure were also evaluated. Equivalence
in CBC, and QOL between P1 and P2 was tested using exact test of equivalence and Westlakes interval.
Needed sample size was 15 patient/group. Ethical committee approved the study.
Results: Spinal cord lesion was traumatic (18), degenerative (8), infectious (3) or malformative (1) in 16
women and 14 men. Table summarizes changes after BTA injection. QOL was signifcantly improved in
both groups until 24 weeks. There was no diference in sex ratio, age or baseline CBC between groups.
Equivalence between P1 and P2 was demonstrated for both CBC and QOL during all the followup. There
was no diference between P1 and P2 in term of NID at 12, 24 and 36 weeks (Mann-Withney). EVA among
patients with preserved sensibility was signifcantly less with P2 (7.2+/-2.2 vs 3.4+/-4.4). No severe side efect
was reported.
Baseline 6w 12w 24w 36w
CBC ml (sd)
30 inj.
259 (30) 441 (27)* 448 (27)* 438 (46)* 386 (63)
CBC ml (sd)
10 inj.
250 (30) 537 (30)* 431 (41)* 382 (38)* 341 (44)
NDI (sd) 4.7 (0.9) 1.0 (0.3)* 1.1 (0.4)* 2.6 (1.1)* 2.9 (1.0)
NDI (sd) 3.5 (0.5) 0.7 (0.3)* 1.0 (0.4)* 1.7 (0.5)* 2.3 (0.5)
Conclusions: Efcacy of bladder injections of 300 units of BTA to treat NDOI was not afected by a threefold
increase in dose per injection point and subsequent threefold decrease in total number of injections. This
observation provides an indirect evidence of a dose dependant difusion of BTA biologic activity within bladder
wall. Practically it allows us to shorten and simplify the procedure decreasing the pain as well as the risk of
technical error or bleeding.


891
DETRUSOR INJECTIONS OF BOTULINUM NEUROTOXIN TYPE A
(BONT/A) FOR THE TREATMENT OF BLADDER SYMPTOMS OF
MULTIPLE SCLEROSIS (MS)
Kalsi V.
1
, Gonzales G.
1
, Apostolidis A.
1
, Popat R.
1
, Elneil S.
1
, Dasgupta P.
2
, Fowler C.J.
1
1
National Hospital for Neurology and Neurosurgery, Uro-Neurology, London, United Kingdom,
2
Guys and
St.Thomass Hospitals, Urology, London, United Kingdom
Introduction & Objectives: Bladder dysfunction as part of a symptom complex of spinal cord involvement
is a common and disabling aspect of MS, the clinical picture being dominated by the symptoms of detrusor
overactivity (DO), namely urinary urgency, frequency and urgency incontinence, leading to a diminished
quality of life (QoL). The benefcial efects of detrusor BoNT/A have been well established in patients with
DO due to spinal cord injury, however there is a paucity of experience with MS patients. We report for the
frst time the efect of only detrusor injections of BoNT/A on the symptoms, urodynamic changes and quality
of life in a selected group of patients with an established diagnosis of MS.
Material & Methods: Data were collected for 43 adults (4 men, 39 women, mean age 45.8 years, range 33
61) with urodynamically proven DO refractory to oral anticholinergics pre, 4 and 16 weeks post BoNT/A
treatment. Pre-treatment 2 patients (4.7%) had an indwelling catheter and 28 (65.1%) were performing clean
intermittent self catheterisation. The patients were treated with 300 units of BOTOX using a minimally
invasive local anaesthetic outpatient injection technique. Changes in the number of micturition episodes
(frequency) and those associated with urgency (urgency), incontinence, and nocturia episodes over 24
hours were analysed from a 4-day voiding diary; urodynamic parameters were evaluated by standard voiding
cystometry and QoL was assessed using the validated disease specifc UDI-6 and IIQ-7 questionnaires, at
all study time points. A positive clinical response was defned as more than a 25% improvement in at least
2 of the voiding diary and urodynamic parameters measured. The paired t test was used to compare data
pre and post treatment.
Results: All patients had a positive clinical response as per criteria stated above. The mean ( standard
error) together with the pre-treatment comparison values are shown in the table below. Highly signifcant
benefts (p<0.001) were recorded in all measured parameters and sustained at all follow-up time points.
Parameter Pre 4 weeks post p Value (pre v 4 weeks)
MCC (mls) 235.622.1 602.933.5 <0.0001
Pdetmax (cmH2O) 51.34.1 26.63.1 <0.0001
Frequency 12.50.7 6.60.4 <0.0001
Nocturia 1.40.2 0.60.1 <0.0001
Incontinence 3.90.5 0.360.1 <0.0001
Urgency 7.70.7 1.70.4 <0.0001
QoL score 21.91.9 9.01.6 0.0002
All patients needed to do CISC post-treatment even the 13 (30.2%) who were not doing so pre-treatment.
The mean duration of benefcial efects was 9.6 months (range 316).
Conclusions: Intradetrusor BoNT/A is exceptionally efcacious in tackling bladder symptoms of MS patients
who have reached a point where 1st line treatments are no longer efective thereby improving their QoL. A
particularly important observation is the necessity for all MS patients to perform CISC post-treatment, and
this has been shown not to adversely afect their QoL.


892
THE IMMEDIATE EFFECT INTRADETRUSOR INJECTIONS OF
BOTULINUM NEUROTOXIN A (BONT/A) ON THE SYMPTOMS OF THE
OVERACTIVE BLADDER SYNDROME
Kalsi V.
1
, Apostolidis A.
1
, Gonzales G.
1
, Elneil S.
1
, Dasgupta P.
2
, Fowler C.J.
1
1
The National Hospital for Neurology and Neurosurgery, Uro-Neurology, London, United Kingdom,
2
Guys and St. Thomas Hospitals, Urology, London, United Kingdom
Introduction & Objectives: Urgency and nocturia, whose pathophysiology is not fully understood,
are now increasingly recognised as the most bothersome symptoms of the OABS. Intradetrusor
BoNT/A injections is an efective treatment for intractable neurogenic or idiopathic detrusor
overactivity (NDO/IDO). Previous studies have shown that at 1 month BoNT/A successfully
suppresses urgency, urgency incontinence and frequency, but its immediate efect has not been
studied. In addition, only one study to date has investigated the efect of BoNT/A on nocturia
showing signifcant improvements at 1, 3, and 6 months. We examined the immediate efect of
intradetrusor BoNT/A on the OABS symptoms by studying the daily changes during the week
succeeding treatment of patients with NDO or IDO.
Material & Methods: Twenty-fve patients, 16 NDO (mean age 44.1 years) and 9 IDO (mean
age 45.6 years, p=0.75), treated with 300U BOTOX (NDO) or 200U BOTOX (IDO) completed
a 4-day voiding diary before and at 4 weeks post treatment and a 7-day diary starting the day
immediately after injections. Patients were participants in a study approved by the local Ethics
Committee. Data were analysed for intra-group daily changes during the 1
st
week and for
further changes at 4 weeks. Parametric t-tests were used for statistical analysis (signifcance at
p<0.05).
Results: No diferences were noted at baseline between the 2 groups in any of the studied
variables: Urgency: NDO 8.10.8, IDO 9.31.7, p=0.46 Incontinence: NDO 3.30.9, IDO
6.31.9, p=0.12 24-hour frequency: NDO 11.40.7, IDO 12.91.3, p=0.26 nocturia: NDO
1.50.3, IDO 2.00.4, p=0.26). NDO: Signifcant improvements in urgency, 24-hour frequency
and nocturia were seen as of Day 2 post-injection, in incontinence as of Day 3 post-injection,
and were sustained at 4 weeks. IDO: The frst signifcant change in urgency, frequency and
incontinence was seen at Day 4 post-treatment. The decrease in urgency was sustained at all
time points thereafter, whereas consistent statistical signifcance was not shown for incontinence
and frequency despite persistent decreases in absolute values. No signifcant changes in nocturia
were seen during the 1
st
week, despite a decrease in mean values as of day 5. All parameters
signifcantly improved at 4 weeks.
Conclusions: Intradetrusor BoNT/A ameliorates all OABS symptoms within the frst week after
treatment, but the pathological sensation of urgency is most rapidly and consistently afected in
both NDO and IDO patients, suggesting an early, sustainable efect on bladder aferent pathways.
Synchronous daily changes in frequency and nocturia suggest an element of nocturia is DO
driven. An earlier trend for change is established in the NDO patients for all symptoms examined
and it is not known if this is due to the toxin dose used or underlying pathophysiology.