A COMPARISON BETWEEN THE RESPONSE OF PATIENTS WITHIDIOPATHIC DETRUSOR OVERACTIVITY AND NEUROGENICDETRUSOR OVERACTIVITY TO THE FIRST INTRADETRUSOR

INJECTION OF BOTULINUM-A TOXIN

ROSHNI POPAT, APOSTOLOS APOSTOLIDIS*, VINAY KALSI, GWENDOLINE GONZALES,CLARE J. FOWLER†,‡ AND PROKAR DASGUPTA§

From the Department of Uro-Neurology, The National Hospital for Neurology and Neurosurgery, University College London Hospitals(RP, AA, VK, GG, CJF, PD) and the Department of Urology, Guys’ and St. Thomas’ Hospitals, The Guy’s King’s and St. Thomas’ School

of Medicine (PD), London, United Kingdom

ABSTRACT

Purpose: Several studies have shown that intradetrusor injections of botulinum neurotoxintype A (BoNT/A) may effectively treat intractable spinal neurogenic detrusor overactivity (NDO),but fewer reports exist on the use of BoNT/A in patients with idiopathic detrusor overactivity(IDO). The purpose of this study was to investigate whether comparable efficacy could bedisplayed in the response of patients with IDO to those with NDO.

Materials and Methods: In a prospective, open label study, patients with urgency, and/or urgencyincontinence due to urodynamically proven intractable detrusor overactivity received 300 units(NDO) or 200 units (IDO) of Botox® injected into the bladder with a minimally invasive outpatienttechnique. Urodynamic maximum cystometric capacity and maximum detrusor pressure duringfilling, frequency of voids (frequency), number of incontinence episodes (leak) and number of voidsassociated with urgency per 24 hours (urgency) from 4-day voiding diaries were compared betweenthe 2 groups at baseline and for changes at 4 and 16 weeks after treatment.

Results: A total of 44 patients with spinal NDO and 31 with IDO were treated. At 16 weeks,mean � standard error maximum cystometric capacity increased from 229.1 � 24.8 to 427.0 �26.9 ml, p �0.0001 in NDO and from 193.6 � 24.0 to 327.1 � 36.1 ml, p�0.0008 in IDO.Maximum detrusor pressure during filling decreased from 60.7 � 6.8 to 26.1 � 3.7 cm H2O, p�0.0001 in NDO and from 62.1 � 10.8 to 45.1 � 8.1 cm H2O, p�0.027 in IDO. Frequencydecreased from 12.3 � 0.7 to 6.6 � 0.6 voids per 24 hours, p �0.0001 in NDO and from 13.6 �1.1 to 8.3 � 0.7, p�0.0002 in IDO. Leak decreased from 3.9 � 0.5 to 0.7 � 0.2 incontinenceepisodes per 24 hours, p �0.0001 in NDO and from 3.2 � 0.8 to 0.6 � 0.3, p�0.0017 in IDO, andurgency decreased from 7.5 � 0.6 to 1.44 � 0.3 episodes per 24 hours, p �0.0001 in NDO and from10.9 � 1.7 to 4.9 � 1.1, p �0.0001 in IDO. The 2 groups were comparable for baseline data, butpercent improvement in urgency was greater in patients with NDO at 4 weeks (78.2% vs 56.3%,p�0.019) and 16 weeks (78.3% vs 50.7%, p�0.013). Of patients with NDO 69% required self-catheterization de novo posttreatment compared with 19.3% of those with IDO.

Conclusions: Patients with intractable IDO respond to intradetrusor BoNT/A with equallysignificant improvements in urodynamic and lower urinary tract symptom parameters as thosewith spinal NDO, despite the lower dose of toxin used.

KEY WORDS: botulinum toxin type A, bladder; reflex, abnormal

Initial reports of the use of intradetrusor injections of bot-ulinum neurotoxin type A (BoNT/A) to treat intractable de-

trusor activity (DO) were in patients with spinal cord injury(SCI) or spinal disease1 and a few patients with idiopathicDO (IDO).2, 3 Since then the use of BoNT/A for DO has beenreported by many other groups worldwide4–6 and the find-ings of a retrospective multicenter study have confirmed itsefficacy in the treatment of neurogenic DO (NDO) of spinalorigin.7 However, there have been fewer published data onits effects in patients with IDO, reports so far being mainly inabstract form.2, 8, 9

Evidence in animals as well as humans suggests that theneural basis for DO following SCI involves the emergence ofa segmental spinal reflex, which is mediated by capsaicinsensitive C fiber afferents, and results in increased parasym-pathetic activity.10, 11 Although no such spinal segmentalreflex is thought to underlie nonneurogenic DO, there is someevidence C fiber mediated activity is important.12, 13 How-ever, if, as has been hypothesized,1 intradetrusor BoNT/A

Submitted for publication December 3, 2004.Supported by Allergan UK.Study received Local Research Ethics Committee approval.* Financial interest and/or other relationship with Ipsen U.K., St.

Peter’s Trust for Kidney, Prostate and Bladder Research, and Aller-gan Ltd U.K.

† Correspondence: The National Hospital for Neurology and Neu-rosurgery, Department of Uro-Neurology, Queen Square, LondonWC1N 3BG (telephone: 0207 837 3611 ext. 3418; FAX: 0207 8134587; e-mail: c.fowler@ion.ucl.ac.uk).

‡ Financial interest and/or other relationship with Ipsen U.K., St.Peter’s Trust for Kidney, Prostate and Bladder Research, MultipleSclerosis Society of Great Britain and Northern Ireland ProjectGrant, Pfizer, Allergan and Medtronic.

§ Financial interest and/or other relationship with the MultipleSclerosis Society of Great Britain and Northern Ireland ProjectGrant, and Allergan.

See Editorial on page 818.

0022-5347/05/1743-0984/0 Vol. 174, 984–989, September 2005THE JOURNAL OF UROLOGY® Printed in U.S.A.Copyright © 2005 by AMERICAN UROLOGICAL ASSOCIATION DOI: 10.1097/01.ju.0000169480.43557.31

984

acts by blocking presynaptic release of acetylcholine from theparasympathetic innervation comparable to its mechanism ofaction in skeletal muscle,14 it would be expected for such anagent to be effective whatever the cause of bladder overac-tivity.

Intradetrusor BoNT/A remains an unlicensed treatmentand the potential for its widespread use will depend on itsefficacy in that larger group of patients with IDO. Therefore,a direct comparison of the response of patients with IDO tothat of those with NDO was indicated and we present herethe results of such a study. Although a direct comparison oftreatment efficacy between NDO and IDO would ideally haveused the same dose and administration protocol, we opted toreduce the dose in the IDO population to lessen the risk ofincomplete bladder emptying. A dose titration study showedthat 300 units of Botox® diluted in 30 ml saline and injectedat 30 detrusor sites is adequate to treat a heterogeneousspinal NDO population, most of whom are already doingintermittent self-catheterization for incomplete bladder emp-tying.1, 7 In a study of patients with IDO treated with 200units Botox® injected in 20 sites, significant improvementsin frequency, incontinence and bladder capacity were report-ed.8 Thus, 200 units of Botox® diluted in 20 ml saline andinjected in 20 detrusor sites appears as an acceptable treat-ment regime for patients with IDO in a comparative study.

MATERIALS AND METHODS

Study design. Patients with a history of urgency, frequencyand/or urgency incontinence (as defined by the InternationalContinence Society)15 for more than a year who could not bemanaged by oral medication with or without use of cleanintermittent self-catheterization (CISC), or who had intoler-able adverse events from therapeutic doses of anticholinergictherapy, were considered for this single center, prospective,open label study. Candidates were assessed with standardsubtraction cystometry using a filling rate of 30 ml perminute, and those with urodynamic evidence of phasic orterminal DO15 were considered suitable to enter the study.Filling was stopped when the patient could no longer delaymicturition or upon terminal DO15 and the volume recordedas the maximum cystometric capacity (MCC). Maximum de-trusor pressure during filling (Pdetmax) was also recorded asthe maximum pressure during phasic or terminal DO. Pa-tients with reduced bladder compliance (increased detrusorpressure at low cystometric capacity)15 in the absence ofobvious DO were excluded from the study. Patients withnonneurogenic DO and urodynamic evidence of bladder out-let obstruction (increased voiding Pdet with reduced urineflow rate) were also excluded from analysis.

Women who were pregnant or breast feeding or planningpregnancy were excluded, as were patients on anticoagulanttherapy, patients with neuromuscular transmission disor-ders, or those taking drugs that might interfere with neuro-muscular transmission (eg aminoglucosides). All participat-ing patients had to be able and willing to perform CISC incase this was required following treatment.

The study was realized as part of a research protocol look-ing into the mechanism of action of BoNT/A in human DO,not a treatment trial, since efficacy had already been dem-onstrated.16 Hence a control group was not included. Thestudy was approved by the Local Research Ethics Committeeand all patients gave written informed consent.

Recruited patients were asked to complete a 4-day bladderdiary at baseline, which recorded the time of voids, inconti-nence episodes, volume voided, residual volume, change ofpads and tablets taken during a 24-hour period. Patientswith no record of incontinence episodes in a 4-day diary wereconsidered completely continent. Patient desire to void wasquantified according to given definitions of a planned void,normal, strong and urgent desire to void. A strong desire to

void was regarded as one that may come on suddenly, inter-rupts routine activities, and cannot be postponed for long asit might then lead to incontinence. An urgent desire to voidwas described as a strong and sudden sensation that cannotbe postponed as it would lead to incontinence.

A minimum of 3 weeks and maximum of 1 year separatedbaseline urodynamics from treatment day. Before treatmenturine was checked with a dipstick and was sent for culture ifpositive for leukocytes and nitrites.

Technique. All patients were treated in an outpatient set-ting. Trimethoprim 100 mg stat was given prophylactically toall patients. Before BoNT/A injections, 20 ml of 2% lignocainegel was instilled intraurethrally (Instillagel, Farco-PharmaGmbh, Cologne, Germany). Two patients received an intra-vesical instillation of 40 ml of 2% lignocaine solution for 20minutes via an indwelling catheter. The bladder was thenaccessed via a standard flexible cystoscope (OlympusKeymed, Milton Keynes, United Kingdom) with a workingchannel of 2.2 mm. Residual urine was drained and thebladder was filled to a volume of 100 ml with 0.9% normalsaline. As part of the research protocol to investigate themechanism of action of BoNT/A, 3 to 4 bladder biopsies weretaken using an Olympus biopsy forceps (FB-21SX-1), from aconsistent area 2 cm above and lateral to the ureteral orifice.The size of the biopsies (1 mm diameter) did not requireapplication of cauterization. Patients with NDO then re-ceived 300 units of Botox® (Allergan Ltd UK) dissolved in 30ml of normal saline injected over 30 different sites whereasthose with IDO 200 units dissolved in 20 ml of normal salineinjected over 20 different sites through a flexible injectionneedle (Olympus, Keymed MAJ-656). Injection sites wereidentified as previously described,1 sparing the trigone atleast 2 cm away from each biopsy site, and separated by adistance of 1 to 1.5 cm. The verbal 11-point Box Scale wasused to grade patient discomfort during the injections.17

Patients were prescribed a 3-day course of trimethoprim100 mg twice daily and were asked to avoid CISC (if alreadyperforming) for 6 hours. Those on anti-incontinence medica-tion were advised to discontinue or reduce the dose of themedication on a self-assessed basis of their symptomaticimprovement.

Followup. At 4 and 16 weeks after treatment, following aclear urine dipstick, patients were reassessed with cystom-etry and bladder diaries as at baseline. Flexible cystoscopywas performed to assess for any changes of the bladder wall.Bladder biopsies were then taken for research purposes.Post-micturition residual volume was examined upon everyfollowup and, if more than 100 ml in a patient with persistentlower urinary tract symptoms (LUTS), they were started onCISC if not performing before treatment, according to ourmanagement protocol.18 Additionally, patients with persis-tent LUTS or who became symptomatic again after initialimprovement had a midstream urine specimen sent for anal-ysis and culture, and antibiotics administered if required.

Clinical response was defined as more than 25% improve-ment in at least 2 of the parameters MCC, Pdetmax, numberof voids per 24 hours (frequency), number of incontinenceepisodes per 24 hours (leak), and number of voids associatedwith urgency per 24 hours (urgency). For analysis purposesthe latter parameter included micturition episodes associ-ated with either a strong or urgent desire to void, as boththese definitions given in the bladder diaries were associatedto some extent with the sensation of urgency. Data were alsoanalyzed for changes in anticholinergic dose and continencerate.

Statistical analysis. Data in each group were expressed asmean � standard error. The Wilcoxon matched pairs t testwas used for group analysis of followup changes. Percentchanges of evaluated parameters from baseline were thencompared between the NDO and IDO groups using theMann-Whitney test.

BOTULINUM TOXIN IN NEUROGENIC VS IDIOPATHIC DETRUSOR OVERACTIVITY 985

RESULTS

A total of 44 patients (9 men, 35 women) with a mean ageof 46.7 (range 21 to 67) years with spinal NDO were treated.Etiology of NDO included multiple sclerosis in 29 patients,SCI in 5, spinal cord tumor or cyst in 2, spina bifida in 2,transverse myelitis in 2, vascular lesions in 2, tropical spasticparaparesis in 1, and tethered cord in 1. A total of 31 patients(18 women, 13 men) with a mean age of 49.1 (range 19 to 80)years with refractory IDO were also treated.

Pretreatment data were comparable between the 2 patientgroups, implying they were equally affected before treatment(table 1). A total of 65 patients (39 with NDO, 26 with IDO)were followed up with urodynamic investigation and/or blad-der diaries at 4 weeks and 46 (29 NDO, 17 IDO) at 16 weeks.All had responded to treatment, according to the predefinedcriteria.

Significant benefits were recorded for all measured param-eters at 4 and 16 weeks in the NDO and IDO groups (tables2 and 3). A reversal of the 4-week improvement began at 16weeks for MCC and leak in the NDO group (table 2) and forPdetmax in the IDO group (table 3).

The percent improvements from baseline at 4 and 16 weeksfor each parameter were comparable between the 2 groups inMCC, Pdetmax, frequency and leak (see figure a to d, table 4).However, a significant difference was noted in the percentdecrease in urgency at 4 weeks in favor of the NDO group(p�0.019) which was maintained at 16 weeks (p�0.013) (seepart e of figure).

Continence. Only 5 patients with NDO (11.6%) and 1 withIDO (3.7%) were completely continent before treatment. At 4weeks complete continence was recorded in 25 of 39 followedup patients with NDO (64.1%) and 13 of 24 with IDO (54.2%),whereas at 16 weeks 16 of 29 (55.2%) NDO and 8 of 14

(57.1%) patients with IDO remained continent. Total conti-nence rates were 60.3% at 4-week and 55.8% at 16-weekfollowup. Of the rest all but 2 (1 NDO, 1 IDO) patientsshowed a lessening in degree of incontinence at both follow-ups.

Medication (table 5). NDO: A total of 33 (76.7%) patientswere on anti-incontinence medication before treatment.There were 17 patients followed up who were able to discon-tinue medication at 4 weeks, and 7 were able to reduce thetreatment dose. Two more patients discontinued medicationat 16 weeks. Mean dose of oxybutynin used was significantlyreduced at 4 and 16-week followup (p�0.004 and p�0.03,respectively).

IDO: Eleven (40.7%) patients were on anti-incontinencemedication before treatment. Four patients discontinued med-ication at 4 weeks, but 2 restarted use at 16 weeks. Numbers ofpatients using medication were insufficient for statistics ondose changes after treatment.

Side effects. The mean discomfort rating for the procedurewas no different (p�0.71) between the NDO (3.2 � 0.3, range0.5 to 9.0) and IDO groups (3.3 � 0.4, range 0.5 to 7). Beforetreatment, no patient with IDO was performing CISC,whereas all but 13 patients with NDO were doing so. Follow-ing treatment the use of CISC became necessary in 9 of these13 (69.2%) patients with NDO and in 6 of 31 (19.3%) withIDO. Two patients (1 NDO, 1 IDO) had macroscopic hema-turia for more than 48 hours after treatment, which wasattributed to followup bladder biopsies. Urinary tract infec-tion developed in 3 patients (1 NDO, 2 IDO), whereas 1patient with IDO had flu-like symptoms.

DISCUSSION

This is the first study, to our knowledge, which directlycompares the response of patients with IDO to those withNDO to intradetrusor injections of BoNT/A. Using a flexiblecystoscope, the procedure performed with the patient underlocal anesthesia in an outpatient setting was equally welltolerated by patients with NDO and those with IDO. Inaccord with previous publications we have shown that pa-tients with spinal NDO respond extremely well to intrade-trusor BoNT/A injections and that the short-term response ofa group with IDO, to at least the first injection, is compara-ble.

For patients with DO who do not respond adequately toanticholinergic medication there has long been an acknowl-edged therapeutic chasm between oral therapy and bladdersurgery. Attempts to fill this with the use of intravesical

TABLE 1. Comparison of baseline data between the NDO andIDO groups

Parameter NDO IDO p Value

MCC (ml) 219.3 � 19.9 209.5 � 21.2 0.83(44) (31)

Pdetmax (cm H2O) 56.7 � 5.2 58.5 � 7.9 0.76(44) (31)

Frequency 12.9 � 0.6 13.2 � 0.8 0.64(43) (27)

Leak 3.9 � 0.5 4.5 � 0.7 0.42(43) (27)

Urgency 7.9 � 0.6 10.6 � 1.4 0.24(42) (27)

TABLE 2. Highly significant (p �0.0001) changes in urodynamic and LUTS parameters for the NDO group

Parameter BeforeTreatment 4 Wks 16 Wks p Value

(4 vs 16 wks)

MCC (ml) 229.1 � 24.8 530.9 � 30.9 427.0 � 26.9 0.0016Pdetmax (cm H2O) 60.8 � 6.8 26.1 � 3.8 26.9 � 2.8 0.78Frequency 12.3 � 0.7 6.2 � 0.7 6.6 � 0.6 0.13Leak 3.9 � 0.5 0.3 � 0.1 0.7 � 0.2 0.049Urgency 7.5 � 0.6 2.0 � 0.8 1.4 � 0.3 0.80

TABLE 3. Significant changes in urodynamic and LUTS parameters for the IDO group

Parameter BeforeTreatment 4 Wks 16 Wks

p Value(pretreatment vs

4 wks, No.)

p Value(pretreatment vs

16 wks, No.)

p Value(4 vs 16 wks)

MCC (ml) 193.6 � 24.0 379.7 � 40.4 327.1 � 36.1 �0.0001, 17 0.0008, 17 0.10Pdetmax (cm H2O) 62.1 � 10.9 31.2 � 6.7 45.1 � 8.1 0.0001, 17 0.027, 17 0.013Frequency 13.6 � 1.1 7.8 � 0.6 8.3 � 0.7 �0.0001, 14 0.0002, 14 0.10Leak 3.2 � 0.8 0.3 � 0.1 0.6 � 0.3 0.006, 14 0.0017, 14 0.25Urgency 10.9 � 1.7 4.0 � 0.8 4.9� � 1.1� 0.002, 14 �0.0001, 14 0.64

BOTULINUM TOXIN IN NEUROGENIC VS IDIOPATHIC DETRUSOR OVERACTIVITY986

vanilloids have been unsuccessful and no such licensed agentexists despite the sound scientific basis of such therapies.10

Augmentation cystoplasty is considered the treatment ofchoice for patients with DO refractory to conservative man-agement, although it is a highly invasive, nonreversible pro-cedure that may be associated with early surgical complica-tions and long-term adverse events.19 Although its efficacyhas been established in neurogenic bladder dysfunction, highlong-term failure rates have been reported in patients withIDO.19 After successful BoNT/A treatment, there is a reduc-tion of storage detrusor pressures in combination with in-creased cystometric capacities and improved compliance, im-plying that this may be a suitable alternative for patients at

high risk for upper urinary tract deterioration. Previous re-ports have confirmed a favorable effect of intradetrusorBoNT/A on bladder compliance in patients with NDO duemainly to SCI, and have additionally shown an improvementin voiding pressures.7 The clinical efficacy of BoNT/A inpatients with NDO appears to be sustained with repeat in-jections, but there are still no reports on the efficacy of repeattreatments in patients with IDO. If it replicates the NDOfindings, it suggests that this minimally invasive treatmentmight accomplish the same targets as invasive surgery.

All patients improved after BoNT/A treatment, althoughcomplete continence was achieved in 60.3%. Continence rateappeared better in patients with NDO at 4 weeks, whereas

Comparison of percent changes in clinical parameters after treatment with intradetrusor BoNT/A between NDO and IDO groups showedthat patients with NDO had greater improvement in urgency at 4 and at 16 weeks (*p�0.019 and **p�0.013, respectively) (e) compared withIDO. Mann-Whitney test was used for statistical comparisons. No difference was noted between 2 groups for percent change in MCC (a),percent change in Pdetmax (b), percent change in frequency (c) and percent change in degree of incontinence (d) at 4 or 16 weeks.

TABLE 4. Comparison of percent changes in clinical parameters

Parameter4 Wks After BoNT/A 16 Wks After BoNT/A

NDO IDO p Value NDO IDO p Value

% � MCC 318.5 � 58.7 166.7 � 38.3 0.054 180.8 � 66.5 111.0 � 45.9 0.29% � Pdetmax 39.0 � 8.7 21.1 � 18.6 0.36 41.6 � 8.3 24.5 � 8.6 0.054% � Freq 45.8 � 3.5 40.0 � 4.8 0.47 43.6 � 3.9 36.3 � 5.1 0.32% � Leak 77.5 � 6.1 79.9 � 9.0 0.77 67.6 � 7.4 70.3 � 10.9 0.88% � Urge 78.2 � 7.0 56.2 � 9.5 0.019 78.3 � 5.1 50.7 � 9.2 0.013

BOTULINUM TOXIN IN NEUROGENIC VS IDIOPATHIC DETRUSOR OVERACTIVITY 987

no difference was noted between the 2 groups at 16 weeks. Alarge multicenter study of patients with NDO reported ahigher rate of complete continence (73%) after BoNT/A treat-ment7 than we have found, possibly due to differences in thepatient population. The majority of the patients in our studyhad NDO due to multiple sclerosis rather than SCI, whichwas the most common diagnosis in the multicenter study.Percent changes in severity of incontinence were similarbetween the 2 groups at both followups, despite the lowerdose used in patients with IDO, signifying possibly a betterresponse for this patient group.

Adverse events directly related to treatment were few,mild and transient in nature. Under our management proto-col,18 69.2% of patients with NDO had to perform de novoCISC after BoNT/A, and despite using a lower dose, post-treatment incomplete emptying associated with LUTS thatnecessitated the use of CISC developed in 19.3% of patientswith IDO. However, in another study of patients with IDOtreated with 300 units Dysport® (equivalent to approxi-mately 100 units Botox® using a dosage conversion based onthe published 3: 1 Dysport®-to-Botox® dose ratios for stri-ated muscle injections)20 displayed no increase in residualvolumes, with significant improvements in 24-hour fre-quency and maximum cystometric capacity 1 month aftertreatment.2 Despite the limited number of reports, such ob-servations suggest that an even lower dose than we used mayachieve significant clinical outcomes while reducing the riskfor posttreatment incomplete emptying in patients with IDO.

The most striking component of the clinical response is ahighly significant reduction in patient reports of urgency,independent of the origin of DO. The pathophysiology ofurgency is not clearly understood, but peripheral afferentnerve neuromodulation has been successfully used to sup-press the sensation of urge in patients with lower urinarytract dysfunction.21 We found that patients with NDO had amore significant reduction in the 24-hour number of micturi-tion episodes associated with urgency compared with thosewith IDO. The lower dose used in the latter would be themost obvious reason for this difference, but possible differ-ences in the pathophysiology of NDO and IDO could also becontributing.

CONCLUSIONS

The mechanism by which BoNT/A produces such excep-tional clinical response is as yet uncertain, but our immuno-histochemical studies have shown a significant reduction ofsuburothelial afferent receptors in the NDO and IDO blad-der. In light of a novel hypothesis proposing that anticholin-ergics may not act simply on the motor innervation of thebladder but through a more complex mechanism,22 it may bethat BoNT/A similarly has a more composite, afferently me-diated action.23 If the long-term responsiveness in IDO is asgood as it is in patients with NDO, BoNT/A, possibly injectedsuburothelially,24 could become an important second line

treatment option for nonneurogenic DO in the armamentar-ium of the practicing urologist.

Allergan UK was the gratis provider of Botox® for researchpurposes.

REFERENCES

1. Schurch, B., Stohrer, M., Kramer, G., Schmid, D. M., Gaul, G.and Hauri, D.: Botulinum-A toxin for treating detrusor hyper-reflexia in spinal cord injured patients: a new alternative toanticholinergic drugs? Preliminary results. J Urol, 164: 692,2000

2. Radziszewski, P. and Borkowski, A.: Botulinum toxin type Aintravesical injections for intractable bladder overactivity. EurUrol Suppl, 1: 134, abstract 526, 2002

3. Harper, M., Popat, R. B., Dasgupta, R., Fowler, C. J. andDasgupta, P.: A minimally invasive technique for outpatientlocal anaesthetic administration of intradetrusor botulinumtoxin in intractable detrusor overactivity. BJU Int, 92: 325,2003

4. Grosse, J., Kramer, G. and Stohrer, M.: Success of repeat detru-sor injections of botulinum A toxin in patients with severeneurogenic detrusor overactivity and incontinence. Eur Urol,47: 653, 2005

5. Grosse, J., Kramer, G. and Stohrer, M.: The use of Dysport®botulinum A toxin for detrusor injections in patients withsevere neurogenic detrusor overactivity. Presented at 33rdannual meeting of the International Continence Society, ab-stract 193, Florence, Italy, October 5–9, 2003

6. Del Popolo, G., Li Marzi, V., Panariello, G. and Lombardi, G.:English botulinum toxin-A in the treatment of neurogenicdetrusor overactivity. Presented at 33rd annual meeting of theInternational Continence Society, abstract 96, Florence, Italy,October 5–9, 2003

7. Reitz, A., Stohrer, M., Kramer, G., Del Popolo, G.,Chartier-Kastler, E., Pannek, J. et al: European experience of200 cases treated with botulinum-A toxin injections into thedetrusor muscle for urinary incontinence due to neurogenicdetrusor overactivity. Eur Urol, 45: 510, 2004

8. Loch, A., Loch, T., Osterhage, J., Alloussi, S. and Stockle, M.:Botulinum-A toxin detrusor injections in the treatment of non-neurologic and neurologic cases of urge incontinence. EurUrol, suppl., 2: 172, abstract 678, 2003

9. Rapp, D. E., Lucioni, A., Katz, E. E., O’Connor, R. C., Gerber,G. S. and Bales, G. T.: Use of botulinum-A toxin for the treat-ment of refractory overactive bladder symptoms: an initialexperience. Urology, 63: 1071, 2004

10. de Groat, W. C., Kawatani, M., Hisamitsu, T., Cheng, C. L., Ma,C. P., Thor, K. et al: Mechanisms underlying the recovery ofurinary bladder function following spinal cord injury. J AutonNerv Syst, suppl., 30: S71, 1990

11. Brady, C. M., Apostolidis, A. N., Harper, M., Yiangou, Y.,Beckett, A., Jacques, T. S. et al: Parallel changes in bladdersuburothelial vanilloid receptor TRPV1 and pan-neuronalmarker PGP9.5 immunoreactivity in patients with neurogenicdetrusor overactivity after intravesical resiniferatoxin treat-ment. BJU Int, 93: 770, 2004

12. Silva, C., Ribeiro, M. J. and Cruz, F.: The effect of intravesicalresiniferatoxin in patients with idiopathic detrusor instability

TABLE 5. Patients and anti-incontinence medication

No./Total No. Ptson Anti-Incontinence

Medication (%)

No. Anti-Incontinence Medication Mean Mg � SEM Anticholinergic Medication Dose (No. pts onmedication)

AnticholinergicsOtherSingleAgent

Anticholinergics� Desmopressin Oxybutinin Tolterodine Propiverine Trospium

NDO:Baseline 33/43 (76.7) 25 2 6 18.8 � 1.9 (17) 4.1 � 0.2 (12) 45 (1) 40 (1)4 Wks 15/39 (38.5) 11 1 3 13.2 � 2.1 (10) 3.2 � 1.1 (4)

16 Wks 10/29 (37.9) 8 1 1 14.3 � 2.3 (7) 4.0 (2)IDO:

Baseline 11/27 (40.7) 9 0 1 27.5 � 2.5 (4) 4.8 � 0.8 (5) 30 (1)4 Wks 4/24 (16.7) 4 0 0 20.0 (1) 5.3 � 1.3 (3)

16 Wks 4/14 (28.6) 4 0 0 20.0 (1) 4.7 � 1.7 (3)Insufficient numbers of patients did not allow for accurate conclusions in other medication categories and in the IDO group.

BOTULINUM TOXIN IN NEUROGENIC VS IDIOPATHIC DETRUSOR OVERACTIVITY988

suggests that involuntary detrusor contractions are triggeredby C-fiber input. J Urol, 168: 575, 2002

13. Chai, T. C., Gray, M. L. and Steers, W. D.: The incidence of apositive ice water test in bladder outlet obstructed patients:evidence for bladder neural plasticity. J Urol, 160: 34, 1998

14. Dolly, O.: Synaptic transmission: inhibition of neurotransmitterrelease by botulinum toxins. Headache, suppl., 43: S16, 2003

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16. Schurch, B., de Seze, M., Denys, P., Chartier-Kastler, E., Haab,F., Everaert, K. et al: Botulinum toxin type A is a safe andeffective treatment for neurogenic urinary incontinence: re-sults of a single treatment, randomized, placebo controlled6-month study. J Urol, 174: 196, 2005

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