Published in May 2010 NAMED PATIENT Programs Named Patient Programs Provide Pre-Launch Access to Drugs The dire outlook facing AML patients motivated a company to provide its drug in advance of the commercial launch. Contributed by Named patient programs (NPPs) enable physi-cians and patients in Europe to access medications JACK V. TALLEY PRESIDENT AND CEO, EPICEPT Medici
Conversely, injection forms, though being painful and needing help of medical personnel for application, help to quickly achieve necessary concentration of preparation in blood buy antibiotics online Antibiotic is usually chosen in an empiric way (at random). But when choosing one is obligatory guided by definite rules.
Doi:10.1016/j.eursup.2008.01.020e u r o p e a n u r o l o g y s u p p l e m e n t s 7 ( 2 0 0 8 ) 5 5 7 – 5 6 5 a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . e u r o p e a n u r o l o g y . c o m Conservative Treatment of Patients with Neurogenic Bladder UZA, Department of Urology, Faculty of Medicine and University Hospital Antwerp, 10 Wilrijkstraat, 2650 Edegem, Belgium Objectives: To review the up-to-date literature of the mostly used con- servative treatment modalities in patients with neurogenic bladder.
Methods: material from literature on conservative management in patients with neurogenic bladder was reviewed. Pubmed search results Results: The conservative treatment is in almost all cases the first and will remain the primary choice in the majority of patients with neuro- genic bladder. Treatment will depend on the type of underlying disease,on the bladder dysfunction, its natural evolution but also on the patients’general condition, and the available resources. Behavioural training,catheters, external appliances, drugs and electrical stimulation are pre-sented, their indications and limitations.
Conclusions: Conservative treatment is the mainstay in neurogenic blad-der management. It offers different methods which permit to success-fully treat most symptoms and conditions in this prevalent LUTpathology.
# 2008 European Association of Urology and European Board of Urology. Published by * Tel. +3238213511; Fax: +3238214479.
E-mail address: .
evolution but also on the patient’s general condition,and the available resources. Urodynamic testing will Neurologic lower urinary tract (LUT) dysfunction is be necessary in many patients to gain more prevalent in many neurological diseases . The complete diagnosis of how the neurogenic dysfunc- condition is known to be life threatening if not tion has changed the function of different compo- properly managed. The conservative treatment is in nenets in the lower urinary tract and their almost all cases the first to give and will remain the primary choice in the majority of patients with This manuscript will not deal specifically with the neurogenic bladder. A good review and listing of period of spinal shock or cerebral shock in acute conservative treatment for neurogenic incontinence neurological lesions when the urologic treatment can be found in the report of ICI 2004 . More actual consists of proper bladder drainage.
For the post shock period or for slowly developing Treatment will depend on the type of underlying dysfunctions several conservative treatments exist disease, on the bladder dysfunction, its natural 1569-9056/$ – see front matter # 2008 European Association of Urology and European Board of Urology. Published by Elsevier B.V. All rights reserved.
e u r o p e a n u r o l o g y s u p p l e m e n t s 7 ( 2 0 0 8 ) 5 5 7 – 5 6 5 Table 1 – Actual principles of conservative management Bladder expression (Crede´ and Valsalva) Stress incontinence due to sphincter incompetence: behavioral/ Bladder expression has been recommended for timed voiding and external appliances.
patients with a combination of an areflexic detrusor Detrusor overactivity with detrusor sphincter dyssynergia: with an areflexic or anatomic incompetent sphinc- intermittent catheterization Æ bladder relaxing drugs; indwel-ling catheter + bladder relaxing drugs.
ter (e.g. after sphincterotomy). Difficulties in empty- Detrusor overactivity with negligible post void residual and no ing may be due to inability to open the bladder neck detrusor sphincter dyssynergia: depending on cooperation and and/or functional obstruction at the level of the mobility: behavioral, bladder relaxant drugs, intermittent cathe- striated external sphincter by the downward move- terization; triggered voiding (if urodynamically safe); external appliances, indwelling catheter + bladder relaxing drugs.
Detrusor underactivity with post void residual: intermittent catheterization; alpha blockers; intravesical electrical stimula- (abdominal straining) and the Cre´de´ (manual com- tion; bladder expression (if urodynamically safe).
pression of the lower abdomen) manoeuvre.
No surgical treatment in this table.
During follow up, more than 50% of patients developed influx into the prostate and the seminalvesicles and other complications, e.g. epididymo- a. Behavioral therapy: Triggered reflex voiding, orchitis. Other complications are reflux into the bladder expression (Crede and Valsalva maneu- upper urinary tract, genital-rectal prolapse and b. Catheters: Intermittent catheterization, indwel- Adjunctive therapy to decrease outflow resis- tance includes alpha-blockers, sphincterotomy or c. Condom catheter and external appliances botulinum toxin injections in the sphincter. If effective they usually cause or increase urinary e. Electro stimulation: Electrical neuromodulation, stress incontinence. The indication is thus limited electrical stimulation of the pelvic floor muscu- and the technique should only be done in patients lature, intravesical electrical stimulation (IVES) where it has been shown to be urodynamically safe.
Behavioural training is often part of the urologicalmanagement in neurologic patients. It consists of Triggering the bladder reflex comprises various different approaches : correcting habit patterns of manoeuvres performed by patients in order to elicit frequent urination, improving ability to control reflex detrusor contractions by exteroceptive sti- bladder urgency, prolonging voiding intervals, muli. Integrity of the sacral reflex arc is mandatory.
increasing bladder capacity, reducing incontinent The most commonly used are suprapubic tapping, episodes, and building patient’s confidence. Keeping thigh scratching and anal/rectal manipulation.
a voiding diary is important in many aspects and can Frequency of use, intervals and duration have to be specified for each patient. Today, triggered Behavioural measures are most valuable in brain voiding should not be done without taking care of diseases as cerebro vascular disease, Parkinson bladder outlet obstruction. Also continence, easy to disease, multiple system atrophy, dementia, and use appliances, gender, level and type (complete or cerebral palsy. Other diseases as multiple sclerosis, incomplete lesions, para- vs quadriplegic patients) incomplete spinal cord injury, transverse myelitis, diabetes mellitus can also be good indications. Frail It is necessary to check if the bladder is elderly neurologic patients who need assistance can functioning in a urodynamic safe way (not too high pressure development). Regular follow-up betweenevery 6 months and every 2 years should be Timed voiding is characterized by a fixed interval guaranteed. To improve emptying, control auto- between toiletting. It is initiated and maintained nomic dysreflexia, and avoid renal damage, alpha- by caregivers and therefore the interval will blockers or botulinum toxin sphincter injections depend both on bladder function and the working can be tried before sphincterotomy and/or bladder schedules of the caregivers. The latter will depend on staffing, number of patients under care and Triggered voiding should not be recommended as facilities available. In our practice it means mostly every 3 hours during daytime and no toileting e u r o p e a n u r o l o g y s u p p l e m e n t s 7 ( 2 0 0 8 ) 5 5 7 – 5 6 5 during the night. Its aim is more to avoid development of urinay tract infection (UTI). There incontinence than to restore a normal bladder exists not one best technique or one best material as function. During the night this is often more both depend greatly on patients’ individual ana- difficult to achieve. Timed voiding has also been tomic, including the possible handling, social and used as an adjunct therapy to tapping and/or Cre´de´ manoeuvre and/or intermittent catheter- Two main techniques have been adopted, a sterile isation. Timed voiding is one of the first steps of IC (SIC), and a clean IC (CIC). The sterile non-touch treating too high bladder volumes as in diabetes technique implicates the use of sterile materials patients with loss of bladder filling sensation.
handled with sterile gloves and forceps. In an Habit retraining has to be inititated and maintained intensive care unit, some advocate wearing a mask by caregivers. It is more indicated for patients with and a sterile gown as well. Mostly used is the clean brain diseases than with spinal cord lesions and technique which can be done almost everywhere.
for patients with cognitive and/or motor deficits.
For aseptic handling, the catheter is moved out of a The aim is to avoid incontinence and/or involun- sterile sheath into the urethra without touching the tary bladder contractions by decreasing voiding catheter itself. Frequency of catheterization will intervals. Such program can be very useful for depend on bladder volume, fluid intake, postvoid Prompted voiding is used to teach people to initiate detrusor pressure). Usually it is recommended to toileting through request for help and with catheterize 4–6 times a day during the acute stage positive reinforcement from caregivers when they after spinal cord lesion. Some will need to keep this frequency if IC is the only bladder emptying. Others Keeping a voiding diary: has been shown to be very will catheterize 1–3 times a day to check and beneficial in early and institutional care.
evacuate residual urine after voiding or on a weeklybasis during bladder retraining. To overcome high Most of behavioural treatment has not been well detrusor pressure, bladder relaxing drugs can be documented in patients with neurological problems indicated. For those who develop a low compliance but they are used as routine in many rehabilitation bladder, upper tract deterioration or severe incon- settings. Studying them on clinical value would be tinence, injection of Botulinum toxin in the bladder wall or surgery as with bladder augmentation maybe necessary.
If catheterization is begun by patients with recurrent or chronic UTI and urinary retention,the incidence of infection decreases and patients may become totally free of infection. If symptomaticinfections occur, improper CIC or misuse often can Intermittent catheterization (IC) and self-catheter- be found. Chronic infection persists if the cause ization (ISC) have become properly introduced remains. Treatment of UTI is necessary if the during the last 40 years In general, the purpose infection become symptomatic. The incidence of of catheterization is to empty the bladder and of IC is urethral strictures increases with a longer follow-up to resume normal bladder storage and regularly as is stone formation . Epididymo-orchitis is complete urine evacuation. With IC and ISC there is rare but can occur . The safety in longterm no need to leave the catheter in the LUT all the time, thus avoiding complications of indwelling catheter- Nocturnal bladder emptying has emerged as a specific treatment for nighttime overdistension of It is clear that IC can improve or make patients the neurogenic bladder, and can reverse or prevent with neurologic bladder continent if bladder capa- city is sufficient, bladder pressure kept low, urethral Proper education and teaching are absolute resistance high enough, and if care is taken to requirements to guarantee success with IC.
balance between fluid intake, residual urine andfrequency of catheterization.
Indwelling urethral catheters – transurethrally (ID)/ The optimal post-void residual indicating the need to start bladder catheterization remains to beclarified, though Dromerick et al demonstrated Long term indwelling catheterization has got very in a series of stroke patients that a post-void residual negative comments for the last decades due to the greater that 150 ml is an independent risk factor for high complication rate: urethral trauma and e u r o p e a n u r o l o g y s u p p l e m e n t s 7 ( 2 0 0 8 ) 5 5 7 – 5 6 5 bleeding, urethritis, fistula due to pressure caused blood vessels. The preferred insertion technique by improper size of the catheter and improper varies by region and country. There is no evidence technique, bladder and renal stones, cystitis, acute that there is one best way to insert the SC though the and chronic urinary tract infection (UTI), bladder neck incompetence, meatus and urethral sphincter Long-term management of the neurogenic blad- erosion, bladder stones and bladder carcinoma.
der with a SC remains a controversial topic in neuro- The complication rate has been shown to be higher urology. Some favor it as a safe and effective than with IC also in recent articles But ID is treatment, while a large number of experts has still used in many patients due to difficulty in personal experience with suprapubic tube compli- performing IC or persistent leakage between catheterisations. In developing countries ID is still The literature on suprapubic catheterization is the method of choice for those with urinary however still limited and most publications are retention or incontinence. Nowadays the compli- 20 years or older. Also here there is room for much cations of ID seem less due to better materials, the use of smaller size catheters and a proper techni-que of securing the catheter. The frequency ofcatheter change is not well studied but change weekly or every two weeks has been shown to be of benefit in patients with recurrent symptomatic UTI. Recent studies showed that the incidence of Male patients with neurogenic bladder and chronic bladder cancer in a group of spinal cord injured urinary incontinence can be candidates for a with ID was similar to that observed in the general condom catheter connected to a urine or leg bag population, but more than 60% of these initially to collect the urine. Some have difficulty in applying presented with muscle-infiltrating bladder cancer CC due to overweight and/or some degree of penile . Hamid however did not find bladder cancer on atrophy or retraction. Long-term use may cause bladder biopsies in patients with a suprapubic bacteriuria but it does not increase the risk of UTI catheter for mean 12.1 years . For prevention of when compared to other methods of bladder UTI, general cleanliness and local hygiene should management. Complications may be less with good be encouraged. If the patient has a symptomatic hygiene, frequent change and maintenance of low UTI, it is important to check for catheter blockade and complications as urinary stones. Encrustationof a catheter is highly predictive of the presence ofbladder stones . Encrustation and blockage of indwelling urethral catheters is primarily broughtabout by infection of the urinary tract by Proteus Drugs are often used in patients with neurogenic mirabilis or other urease-producing species. To bladder. They aim at decreasing detrusor activity, prevent encrustation, urease inhibitors high increasing bladder capacity and/or increasing/ fluid intake valve regulated release of urine decreasing bladder outlet resistance. The effective- ness of drugs for the treatment of detrusor/sphinc- balloons with triclosan and regular catheter ter dyssynergia is not well documented.
change do seem to have an effect. Cranberry juice Pharmacologic therapy alone has been most , and catheter type offer little help, Routine helpful in patients with relatively mild degrees of antibiotic prophylaxis for patients with SC or ID is neurologic bladder dysfunction. When more severe not recommended . Symptomatic urinary infec- bladder disturbances are present drugs will mostly tions have to be treated with the most specific, support other forms of management such as narrowest spectrum antibiotics available for the A suprapubic catheter minimises the risk of Drugs for neurogenic detrusor over activity (NDO) urethral trauma in men and women, of urethral destruction in neurologically impaired women witheven relatively short-term indwelling urethral catheters, and of urethral pain. The key disadvan- Antimuscarinic agents are by far the most used tage is that it requires a minor ‘surgical’ act to insert pharmacologic agents in the symptomatic manage- the suprapubic catheter with potential to injury ment NDO. The doses have to be chosen individually adjacent structures as the intestine or paravesical e u r o p e a n u r o l o g y s u p p l e m e n t s 7 ( 2 0 0 8 ) 5 5 7 – 5 6 5 220.127.116.11. Oxybutynin. Oxybutynin hydrochloride is a Solifenacin and Darifenacin must be mentioned, moderately potent antimuscarinic agent with a although there are no specific studies on neurogenic pronounced muscle relaxant activity and local detrusor overactivity so far available with them.
Oral administration effectivity has been shown in 18.104.22.168. Flavoxate. Flavoxate hydrochloride has a direct many publications . Side effects as dry mouth inhibitory action on detrusor smooth muscle in proved significantly lower with oxybutynin XL than vitro. The ICI report states that several randomized with immediate-release oxybutynin Transder- controlled studies have shown that the drug has mal oxybutynin is another therapeutic option essentially no effects on detrusor overactivity there- avoiding most of the side effects, but no clinical fore it is not recommended in the treatment of NDO studies are as yet available in neurologic patients.
Intravesical application prolongs the systemic effectof oxybutynin . But oxybutynin can produce 22.214.171.124. Tricyclic Antidepressants. Many clinicians have central nervous system side effects Intravesical found tricyclic antidepressants, particularly imipra- electromotive administration of oxybutynine solu- mine hydrochloride, to be useful agents for facil- tion is believed to increase bioavability and toler- itating urine storage, both by decreasing bladder ance . Intrarectal administration of oxybutynin contractility and by increasing outlet resistance.
has been found clinically valuable but has not been However, no controlled trials of tricyclic antidepres- sants in NDO have been reported. Nevertheless insome developing countries tricyclic antidepressants are the only bladder relaxant substances which benzylic acid derivative with musculotropic (cal- people can afford. But caution is warranted .
cium antagonistic) activity and moderate antimus-carinic effects.
Drugs for blocking nerves innervating the bladder It has a well documented effectiveness and a favourable tolerability and safety profile The vanilloids, capsaicin and resiniferatoxin, acti- 126.96.36.199. Trospium. Trospium is a quaternary ammo- vate nociceptive sensory nerve fibers through an ion channel, known as vanilloid receptor subtype 1 actions, its effectiveness and safety was confirmed (VR1). Activation of VR1 results in spike-like cur- by meta-analysis It does not break the blood– rents, and selectively excites and subsequently brain barrier. Central nervous system side effects desensitizes C-fibers. Capsaicin-desensitization is defined as a long lasting, reversible suppression ofsensory neuron activity . Resiniferatoxin (RTX) is 188.8.131.52. Tolterodine. Tolterodine is a competitive mus- approximately 1,000 times more potent than cap- carinic receptor antagonist with a better tolerability saicin, based on the Scoville Heat Scale. Like and comparable efficacy than oxybutynine. Pub- capsaicin, it possesses vanilloid receptor agonist lished reports on the specific effect on NDO have activity, resulting in desensitization However, shown the therapeutic effects of increased dosage RTX acts without the potent neuronal excitatory effect of capsaicin, and therefore elicits less dis-comfort. RTX has been found superior to capsaicin, 184.108.40.206. Propantheline. Propantheline bromide was the causes less inflammatory side effects . But classically described oral antimuscarinic drug.
Despite its success in uncontrolled case series, norecent controlled study of this drug for NDO are Botulinum toxin A (BTX) has taken a substantialplace in the treatment of neurogenic bladder.
220.127.116.11. Oxyphencyclimine. Oxyphencyclimine is a cheap Though invasive it is still discussed here as it is antimuscarinic that was used originally for treat- being used in ambulatory setting and as adjunctive treatment in many conservative techniques. The Due to its availability and very low cost, oxy- toxin acts by inhibiting acetylcholine release at the phencyclimine may be an alternative bladder presynaptic cholinergic junction. It can also mod- relaxant for SCI patients in developing countries ulate abnormal sensory function Inhibited where other potent bladder relaxant drugs are not acetylcholine release results in regionally decreased muscle contractility and muscle atrophy at the site e u r o p e a n u r o l o g y s u p p l e m e n t s 7 ( 2 0 0 8 ) 5 5 7 – 5 6 5 of injection though such atrophy has not been seen supraspinal level. Neuromodulation in its different in the smooth bladder muscle The chemical forms would either activate the striated urethral denervation results in a reversible process as axons sphincter causing reflexively detrusor relaxation resprout in approximately 3–6 months.
either activate afferent fibers causing inhibition at a The drug is used for detrusor overactivity and for sphincter overactivity Many studies are Publications have described effects in patients published and experience grows on the long term with Parkinson’s disease, spinal cord lesion, multi- effect of repeated injections. Overall the results are satisfactory and the safety is good There have There are no significant data available so far on been publications so far showing that BTX injections the clinical value of magnetic stimulation.
in sphincter /or detrusor can cause transient general Electrical stimulation of the pelvic floor musculature muscle weakness . Some caution is warranted aims in patients with neurologic urinary stress about these and other side effects and it is incontinence to improve strength and timing of recommended to evaluate these further as more the pelvic floor muscle contraction. It has been used patients get treated this way. Today these rare side with different wave forms, frequencies, intensities, effects do not change the clinical value of the treatment. Botulinum B does seem to have insuffi- In patients with incomplete denervation of the pelvic floor muscle and of the striated sphincter,electrostimulation may improve pelvic floor func- - new suggested treatments promising results are given with intravesical atropine and 1 mg ofthe endogenous peptide nociceptin/orphanin FQ Intravesical electrical stimulation (IVES) Intravesical electrical stimulation of the bladder Drugs for neurologic sphincter deficiency (IVES) is still a controversial therapy for patientswith neurologic detrusor dysfunction despite its Alpha-adrenergic agonists, estrogens, beta-adrener- gic agonists and tricyclic antidepressants have been The mechanisms involved in eliciting bladder used to increase outlet resistance but no studies on contraction with IVES are still uncertain though the their use in neurogenic sphincter deficiency have technique has been used in clinical practice for been published. The information remains so far several decades. Some authors consider IVES responses while others think they are a direct bladder muscle effect IVES is an option toinduce/improve bladder sensation and to enhance Alpha adrenergic antagonists as have been reported to the micturition reflex in incomplete central or be possibly useful in neurogenic bladder in the facilitation of storage and emptying, and in theprevention of autonomic dysreflexia. Cholinergics as bethanechol chloride seems to be of limited benefit for detrusor a/hypocontractility.
Work is under way both from the NeurourologyGuidelines Committee of EAU and from the Neu- rourology working group of the International Con-sultation on Incontinence (ICI) 2008 that will present full reports this year with level of evidence and gradeof recommendations for all treatments mentioned The current techniques of neuromodulation used mainly for treating detrusor overactivity are (a)anogenital ES, (b) transcutaneous electrical nervestimulation (TENS), (c) sacral nerve neuromodula-tion, (d) percutaneous posterior tibial nerve stimula- tion (Stoller afferent nerve stimulation, SANS) and(e) magnetic stimulation. It is suggested that  Wyndaele JJ, Castro D, Madersbacher H, et al. Neurologic neuromodulation works at a spinal and at a urinary and faecal incontinence. In: Abrams P, Cardozo L, e u r o p e a n u r o l o g y s u p p l e m e n t s 7 ( 2 0 0 8 ) 5 5 7 – 5 6 5 Khoury S, Wein A, editors. Incontinence. Edition.
chronic suprapubic indwelling catheters: is it valid? J Urol Chapter 17, Committee 12. Health Publications; 2005. p.
 Linsenmeyer MA, Linsenmeyer TA. Accuracy of predict-  Murnaghan GF. Neurologic disorders of the bladder in ing bladder stones based on catheter encrustation in Parkinsonism. Br J Urol 1961;33:403–9.
individuals with spinal cord injury. J Spinal Cord Med  Litwiller SE, Frohman EM, Zimmern PE. Multiple sclerosis and the urologist. J Urol 1999;161:743–57.
 Burns JR, Gauthier JF. Prevention of urinary catheter  Hampel C, Gillitzer R, Pahernik S, Melchior S, Thuroff JW.
incrustations by acetohydroxamic acid. J Urol 1984; Diabetes mellitus and bladder function. What should be considered. Urologe 2003;42:1556–63.
 Morris NS, Stickler DJ. Does drinking cranberry juice pro-  Seski JC, Diokno AC. Bladder dysfunction after radical duce urine inhibitory to the development of crystalline, abdominal hysterectomy. Am J Obstet Gynecol 1977; catheter-blocking Proteus mirabilis biofilms? BJU Int  Linsenmeyer TA, Horton J, Benevento J. Impact of alpha1-  Sabbuba NA, Stickler DJ, Long MJ, Dong Z, Short TD, blockers in men with spinal cord injury and upper tract Feneley RJ. Does the valve regulated release of urine from stasis. J Spinal Cord Med 2002;25:124–8.
the bladder decrease encrustation and blockage of  Hadley EC. Bladder training and related therapies for indwelling catheters by crystalline proteus mirabilis bio- urinary incontinence in older people. JAMA 1986;  Jones GL, Russell AD, Caliskan Z, Stickler DJ. A strategy for  Dowd T, Kocaba K, Steiner R. Using cognitive startegies to the control of catheter blockage by crystalline Proteus enhance bladder control and comfort. Holist Nurs Pract mirabilis biofilm using the antibacterial agent triclosan.
 Wyndaele JJ. Editorial comment on: a novel product for  Morris NS, Stickler DJ, Winters C. Which indwelling ure- intermittent catheterisation: its impact on compliance thral catheters resist encrustation by Proteus mirabilis with daily life—international multicentre study. Eur Urol biofilms? Br J Urol 1997;80:58–63.
 Biering-Sorensen F, Bagi P, Hoiby N. Urinary tract infec-  Dromerick AW, Edwards DF. Relation of postvoid residual tions in patients with spinal cord lesions: treatment and to urinary tract infection during stroke rehabilitation.
prevention. Drugs 2001;61:1275–87.
Arch Phys Med Rehabil 2003;84:1369–72.
 Siroky MB. Pathogenesis of bacteriuria and infection in  Wyndaele JJ. Intermittent catheterization: which is the the spinal cord injured patient. Am J Med 2002;113(Suppl optimal technique? Spinal Cord 2002;40:432–7.
 Chen Y, DeVivo MJ, Lloyd LK. Bladder stone incidence in  Madersbacher H, Wyndaele JJ, Igawa Y, Chancellor M, persons with spinal cord injury: determinants and trends, Chartier-Kastler E, Kovindha A. Conservative manage- 1973–1996. Urology 2001;58:665–70.
ment in neuropathic urinary incontinence. In: Abrams  Wyndaele JJ, Maes D. Clean intermittent self-catheteriza- P, Cardozo L, Khoury S, Wein A, editors. Incontinence.
tion: a 12-year followup. J Urol 1990;143:906–8.
Health publication; 2002. p. 697–754, chapter 10.
 Ku JH, Jung TY, Lee JK, Park WH, Shim HB. Influence of  O’Leary M, Erickson JR, Smith CP, McDermott C, Horton J, bladder management on epididymo-orchitis in patients Chancellor MB. Effect of controlled-release oxybutynin on with spinal cord injury: clean intermittent catheterization neurologic bladder function in spinal cord injury. J Spinal is a risk factor for epididymo-orchitis. Spinal Cord  Lehtoranta K, Tainio H, Lukkari-Lax E, Hakonen T, Tam-  Lindehall B, Abrahamsson K, Jodal U, Olsson I, Sille´n U.
mela TL. Pharmacokinetics, efficacy, and safety of intra- Complications of clean intermittent catheterization in vesical formulation of oxybutynin in patients with young females with myelomeningocele: 10 to 19 years detrusor overactivity. Scand J Urol Nephrol 2002;36: of followup. J Urol 2007;178:1053–5.
 Canon S, Alpert S, Koff SA. Nocturnal bladder emptying  Ferrara P, D’Aleo CM, Tarquini E, Salvatore S, Salvaggio E.
for reversing urinary tract deterioration due to neuro- Side-effects of oral or intravesical oxybutynin chloride in genic bladder. Curr Urol Rep 2007;8:60–5.
children with spina bifida. BJU Int 2001;87:674–8.
 Turi MH, Hanif S, Fasih Q, Shaikh MA. Proportion of  Di Stasi SM, Giannantoni A, Vespasiani G, et al. Intrave- complications in patients practicing clean intermittent sical electromotive administration of oxybutynin in self-catheterization (CISC) vs indwelling catheter. J Pak patients with detrusor hyperreflexia unresponsive to standard anticholinergic regimens. J Urol 2001;165:491–8.
 Biering-Sorensen F. Urinary tract infection in individuals  Radziszewski P, Borkowski A. Therapeutic effects of with spinal cord lesion. Curr Opin Urol 2002;12:45–9.
intrarectal administration of oxybutynin. Wiad Lek  Pannek J. Transitional cell carcinoma in patients with spinal cord injury: a high risk malignancy? Urology  Madersbacher H, Murtz G. Efficacy, tolerability and safety profile of propiverine in the treatment of the overactive  Hamid R, Bycroft J, Arya M, Shah PJ. Screening cystoscopy bladder (non-neurologic and neurologic). World J Urol and biopsy in patients with neurologic bladder and e u r o p e a n u r o l o g y s u p p l e m e n t s 7 ( 2 0 0 8 ) 5 5 7 – 5 6 5  Frohlich G, Bulitta M, Strosser W. Trospium chloride in  Hirst GR, Watkins AJ, Guerrero K, Wareham K, Emery SJ, patients with detrusor overactivity: meta-analysis of pla- Jones DR, et al. Botulinum toxin B is not an effective cebo-controlled, randomized, double-blind, multi-center treatment of refractory overactive bladder. Urology clinical trials on the efficacy and safety of 20 mg trospium  Fader M, Glickman S, Haggar V, Barton R, Brooks R, Malone-Lee J. Intravesical atropine compared to oral oxy-  Horstmann M, Schaefer T, Aguilar Y, Stenzl A, Sievert KD.
butynin for neurogenic detrusor overactivity: a double- Neurogenic bladder treatment by doubling the recom- blind, randomized crossover trial. J Urol 2007;177:208–13.
mended antimuscarinic dosage. Neurourol Urodyn  Lazzeri M, Calo` G, Spinelli M, et al. Daily intravesical instillation of 1 mg nociceptin/orphanin FQ for the control  Kitisomprayoonkul W, Kovindha A. The efficacy of oxy- of neurogenic detrusor overactivity: a multicenter, pla- phencyclimine hydrochloride in treatment of urinary cebo controlled, randomized exploratory study. J Urol incontinence in spinal cord injured patients with detrusor sphincter dyssynergia. J Thai Rehabil 2000;10:23–6.
 Abrams P, Amarenco G, Bakke A, et al., European Tam-  Andersson KE. Current concepts in treatment of disorders sulosin Neurogenic Lower Urinary Tract Dysfunction of micturition. Drugs 1988;35:477–94.
Study Group. Tamsulosin: efficacy and safety in patients  Chancellor MB, de Groat WC. Intravesical capsaicin and with neurogenic lower urinary tract dysfunction due to resiniferatoxin therapy: spicing up the ways to treat the suprasacral spinal cord injury. J Urol 2003;170:1242–51.
overactive bladder. J Urol 1999;162:3–11.
 Lewis JM, Cheng EY. Non-traditional management of the  Lazzeri M, Spinelli M, Zanollo A, Turini D. Intravesical neurogenic bladder: tissue engineering and neuromodu- vanilloids and neurogenic incontinence: ten years experi- lation. ScientificWorldJournal 2007;7:1230–41.
 Dalmose AL, Rijkhoff NJ, Kirkeby HJ, Nohr M, Sinkjaer T,  Kim JH, Rivas DA, Shenot PJ, Green B, Kennelly M, Erickson Djurhuus JC. Conditional stimulation of the dorsal penile/ JR, et al. Chancellor MB Intravesical resiniferatoxin for clitoral nerve may increase cystometric capacity in refractory detrusor hyperreflexia: a multicenter, blinded, patients with spinal cord injury. Neurourol Urodyn randomized, placebo-controlled trial. J Spinal Cord Med  Lee YH, Creasey GH. Self-controlled dorsal penile nerve  de Se`ze M, Gallien P, Denys P, Labat JJ, Serment G, Grise P, stimulation to inhibit bladder hyperreflexia in incomplete et al. Intravesical glucidic capsaicin versus glucidic sol- spinal cord injury: a case report. Arch Phys Med Rehabil vent in neurogenic detrusor overactivity: a double blind  Keppene V, Mozer P, Chartier-Kastler E, Ruffion A. Neu- romodulation in the management of neurogenic lower  Apostolidis A, Dasgupta P, Fowler CJ. Proposed mechan- urinary tract dysfunction. Prog Urol 2007;17:609–15.
ism for the efficacy of injected botulinum toxin in the  Roth TM. Sacral neuromodulation and lower urinary tract treatment of human detrusor overactivity. Eur Urol dysfunction in cerebral palsy. Int Urogynecol J Pelvic Floor  Haferkamp A, Schurch B, Reitz A, Krengel U, Grosse J,  Krivoborodov GG, Gekht AB, Korshunova ES. Tibial neu- Kramer G, et al. Lack of ultrastructural detrusor changes romodulation in the treatment of neurogenic detrusor following endoscopic injection of botulinum toxin type A hyperactivity in patients with Parkinson’s disease. Uro- in overactive neurogenic bladder. Eur Urol 2004;46:784–91.
 Reitz A, Sto¨hrer M, Kramer G, et al. European experience  Ishigooka M, Hashimoto T, Izumiya K, Katoh T, Yaguchi H, of 200 cases treated with botulinum-A toxin injections Nakada T, et al. Electrical pelvic floor stimulation in the into the detrusor muscle for urinary incontinence due to management of urinary incontinence due to neuropathic neurologic detrusor overactivity. Eur Urol 2004;45:510–5.
overactive bladder. Front Med Biol Eng 1993;5:1–10.
 Kuo HC. Effect of botulinum a toxin in the treatment of  McClurg D, Ashe RG, Lowe-Strong AS. Neuromuscular voiding dysfunction due to detrusor underactivity. Urol- electrical stimulation and the treatment of lower urinary tract dysfunction in multiple sclerosis – a double blind,  de Seze M, Petit H, Gallien P, et al. Botulinum A toxin and placebo controlled, randomised clinical trial. Neurourol detrusor sphincter dyssynergia: a double-blind lidocaine- controlled study in 13 patients with spinal cord disease.
 Ebner A, Jiang CH, Lindstro¨m S. Intravesical electrical stimulation-An experimental analysis of the mechanism  Schurch B. Botulinum toxin for the management of blad- der dysfunction. Drugs 2006;66:1301–18.
 Buyle S, Wyndaele JJ, D’Hauwers K, Wuyts F, Sys S. Opti-  Dykstra DD, Sidi AA. Treatment of detrusor-sphincter mal parameters for transurethral intravesical electrosti- dyssynergia with botulinum A toxin: a double-blind mulation determined in an experiment in the rat. Eur Urol study. Arch Phys Med Rehabil 1990;71:24–6.
 Wyndaele JJ, Van Dromme SA. Muscular weakness as side  Madersbacher H. Intravesical electrical stimulation for effect of botulinum toxin injection for neurologic detrusor the rehabilitation of the neuropathic bladder. Paraplegia overactivity. Spinal Cord 2002;40:599–600.
e u r o p e a n u r o l o g y s u p p l e m e n t s 7 ( 2 0 0 8 ) 5 5 7 – 5 6 5 C. Is not to be used in patients with brain D. Aims more to avoid incontinence than to answer these EU-ACME questions on-line. The EU- ACME credits will then be attributed automatically.
4. Intermittent catheterization (IC) and self-cathe- 1. Triggered reflex voiding comprises various man- terization (ISC) are nowadays used very fre- oeuvres performed by patients in order to elicit reflex detrusor contractions by exteroceptive A. Catheterization should be done less than 3 A. The most commonly used technique is strain- B. Balance must be made between fluid intake, residual urine and frequency of catheterization.
B. Integrity of the sacral reflex arc is not C. Control for UTI on a regular basis is unneces- C. Triggered voiding should not be recommended D. Urodynamic investigation is unnecessary.
D. Alpha adrenergic stimulators can facilitate the 5. Indwelling catheter (ID) use is considered nega- tive as the complication rate is high. But ID is stillused in many patients due to difficulty in 2. Bladder expression has been recommended for performing IC or persistent leakage between patients with a combination of an areflexic catheterisations. In developing countries ID is detrusor with an areflexic or anatomic incompe- tent sphincter (e.g. after sphincterotomy): A. Incidence of bladder cancer in spinal cord A. Integrity of the sacral reflex arc is not injured treated with ID is higher than in the B. The most commonly used technique is gently B. 60% of bladder cancers found in patients with C. The technique has a wide indication after D. With symptomatic UTI antibiotics are prohib- 3. Behavioural training is often part of the urological management in neurologic patients. It consists of 6. Botulinum toxin A (BTX) has taken a substantial different techniques as correcting habit patterns place in the treatment of neurogenic bladder. The of frequent urination, improving ability to control drug is used for detrusor overactivity and for bladder urgency, prolonging voiding intervals, increasing bladder capacity, reducing incontinent A. The substantial literature shows low efficacy.
A. Is characterized by a flexible interval between C. Repeating the treatment is seldom needed.
D. Transient general muscle weakness can hap- B. Needs very little effort from caregivers.
Journal of Antimicrobial Chemotherapy (2006) 57, 142–145doi:10.1093/jac/dki389Advance Access publication 10 November 2005First outbreak of multidrug-resistant Klebsiella pneumoniae carryingblaVIM-1 and blaSHV-5 in a French university hospitalNajiby Kassis-Chikhani1,2, Dominique Decre´3*, Vale´rie Gautier3, Be´atrice Burghoffer3,Faouzi Saliba4, Daniele Mathieu1, Didier Samuel4, Denis Cas