[Therapy-refractory overactive bladder: alternative treatment approaches]. / Die therapierefraktäre überaktive Blase : Alternative Therapieansätze.

The treatment of patients with overactive bladder (OAB) refractory to conventional treatment is gaining clinical significance. This article intends to review alternative therapy options for patients with OAB refractory to conventional treatment. A search of the PubMed database as well as the abstracts presented at the European Association of Urology and the American Urological Association annual meetings was conducted. Keywords used during this search included overactive bladder (OAB) refractory to conventional treatment, electromotive drug administration (EMDA), sacral neuromodulation, augmentation cystoplasty and cystectomy. Eighteen articles with an adequate number of patients were identified. All articles published before 2001 were not included in this analysis. Because of first-line treatment failure, 30% of the patients required alternative treatment. This included EMDA, botulinum toxin injections into the detrusor, sacral neuromodulation, augmentation cystoplasty or cystectomy. Based on this review it appears that a significant improvement in micturition parameters, continence and in quality of life was achieved. Overall EMDA, intradetrusor injections of botulinum toxin and sacral neuromodulation seem to be highly effective and safe. Augmentation cystoplasty or cystectomy remains the last choice of treatment in refractory cases.Overall EMDA, intradetrusor injections of botulinum toxin and sacral neuromodulation seem to be highly effective and safe. Augmentation cystoplasty or cystectomy remains to be the last choice of treatment in refractory cases.

[Botulinum toxin in the treatment of benign prostatic hyperplasia : an overview]. / Botulinumtoxin in der Therapie der benignen Prostatahyperplasie : Ein Uberblick.

The aim of this article is to provide a state-of-the-art review about the treatment of benign prostatic hyperplasia with botulinum toxin injections into the prostate. We searched PubMed for original articles until July 2007. Abstracts published at international congresses were also considered if they contributed substantial new information. Injections were performed mostly via the transperineal route under local anesthesia.From this review it appears that a majority of patients with benign prostatic hyperplasia experiences an improvement of both subjective parameters (IPSS, AUA symptom score) and objective parameters such as peak flow rate, postvoid residual volume, and prostate volume. An effect could be shown for different patient groups including different prostate sizes and different symptom characteristics. A high success rate and sustained duration of the effect of at least 12 months could be achieved. Side effects were marginal, and no systemic side effects were reported.Placebo-controlled studies with sufficient patient numbers and long-term follow-up are needed to determine the future value of this procedure in the treatment of patients with benign prostatic hyperplasia.

[Botulinum toxin A injection for treatment-refractory giggle incontinence]. / Botulinumtoxin-A-Injektion bei therapierefraktärer Giggle-Inkontinenz.

A 20-year-old woman reported about giggle incontinence despite antimuscarinic therapy. Therefore we injected botulinum toxin A into the detrusor muscle. The effect of botulinum toxin A appeared about 1 week after injection and no more leakage was observed even during vigorous laughter. A control uroflowmetry showed a good voiding rate without any residual volume. Botulinum toxin A might be an alternative for patients with giggle incontinence after unsuccessful antimuscarinic treatment.

[Use of permanent electrodes in the peripheral nerve evaluation test (PNE-Test) in comparison to conventional wire electrodes]. / Einsatz permanenter Elektroden beim peripheren Nervenevaluation-Test (PNE-Test) im Vergleich zur herkömmlichen Drahtelektrode.

PURPOSE: Prior to implantation of a chronic sacral neurostimulator, it is important to establish which patients might profit from this kind of therapy in order to ensure, by means of a PNE (peripheral nerve evaluation) test, that the implantation of a permanent stimulating device is effective. In this study we compared the two different techniques used in our department (implantation of the permanent neurostimulation electrodes, the so-called "two-stage-implantation" vs. conventional PNE). MATERIALS AND METHODS: We performed a sacral nerve stimulation in 53 patients (mean age: 49.7 years, range: 14 - 75 years) over a minimum of 5 days. In 42 patients we performed a conventional PNE, 11 patients underwent "two-stage implantation" with implantation of the permanent electrodes. RESULTS: 52 of 53 patients received bilateral test stimulation (9 % at S2, 91 % at S3). One patient underwent unilateral PNE (S3) because of an anatomic deformity of the os sacrum. In 20 cases the conventional PNE-test (cPNE) was successful according to standard criteria (47.6 % of all cPNE). The response rate of "two-stage implantation" with implantation of the permanent electrodes was 81.8 % (9 of 11 patients). CONCLUSIONS: The success rate of implantation of permanent neurostimulation electrodes in selecting patients for the permanent implant is significantly higher than the conventional PNE. In this group patients with neurogenic and overactive bladder dysfunctions showed the highest response rates to sacral nerve stimulation and are the most likely to benefit from sacral neuromodulation.

Endothelin-A-receptor antagonist LU 302146 inhibits electrostimulation-induced bladder contractions in vivo.

OBJECTIVES: Endothelin (ET) is a strong constrictor of smooth muscle structures. The relevance of Endothelin-A receptors in the bladder was demonstrated in several in vitro studies. The aim of this functional study was to evaluate the acute effect of the selective ET-A-antagonist LU 302146 (LU) on neurostimulation-induced bladder contractions in vivo. METHODS: Eight male mini pigs were anesthesized. The bladder was exposed and a double lumen catheter was inserted to perform intravesical pressure (pves) measurements. Laminectomy was performed for sacral anterior root stimulation (SARS) of S2. Four animals received the selective ET-A-antagonist LU, three atropine and one animal was treated with vehicle. Pves was recorded before and after drug administration as well as before and during neurostimulation. At the end of each LU trial, a supplementary application of 4 mg atropine was administered followed by a final SARS. RESULTS: In all experiments reproducible pves values were elicited during electrostimulation before administration of the test substance. The selective ET-A-antagonist reduced stimulation-induced bladder contraction by a mean of 57%. Additional administration of atropine inhibited the detrusor contraction almost completely during SARS. The vehicle had no effect on bladder contraction. CONCLUSIONS: In the presented animal model, ET-1 inhibition with the selective ET receptor-A-antagonist LU 302146 decreases stimulation-induced bladder contraction in vivo. The results suggest that the selective ET-A antagonist LU acts on the atropine-resistant component of efferent detrusor activation since additional administration of atropine almost completely abolish detrusor contraction. This observation in addition to the involvement of ET-1 in bladder smooth muscle proliferation, raises the possibility that ET-receptor antagonists might be beneficial in patients with neurogenic bladder dysfunction or in patients with functional or anatomical BOO.

[Pudendal nerve stimulation therapy of the overactive bladder -- an alternative to sacral neuromodulation?]. / Chronische Pudendale Neurostimulation zur Therapie der überaktiven Blase -- eine Alternative zur sakralen Neuromodulation?

PURPOSE: Sacral neuromodulation is known to be an alternative therapeutic option for patients with anticholinergic resistant overactive bladder (OAB). For the same indication, a microstimulation system called BION is available since last year. The BION-stimulator, which only measures 2.8 x 0.3 cm, is designed for pudendal nerve stimulation. Its implantation technique as well as the first clinical results are presented and discussed. MATERIALS AND METHODS: During an outpatient percutaneous screening test (PST), a pudendal nerve stimulation is performed with a needle electrode in local anesthesia. A 50 % increase in the urodynamic parameters (bladder capacity, first desire to void, compliance, etc.) is an indication for a chronic implantation of the BION stimulator, which also can be placed in local anesthesia. RESULTS: Two patients have been treated with a BION-stimulator in our clinic so far. Patient I suffered from an OAB with frequent urinary incontinence and patient II had a sensory OAB with high voiding frequency. After the BION(R)-implantation, patient I showed a reduction in incontinence episodes by 31.5 % a day and patient II had lowered voiding frequencies from 12.6 to 7 a day. The postoperative urodynamic investigations confirmed these clinical results. CONCLUSIONS: The BION-system and chronic pudendal nerve stimulation seem to be alternatives to sacral neuromodulation, however, patient selection is difficult as subchronic stimulation for a longer period of time is not possible so far.

Deafferentation of the urinary bladder and implantation of a sacral anterior root stimulator (SARS) for treatment of the neurogenic bladder in paraplegic patients.

Since 25 years electrical stimulation has become an established and widely acknowledged therapy option. Today, FES is widely employed, e.g. for cardiostimulation, diaphragm stimulation, kinetotherapy, for treatment of tremor in Parkinson patients, and finally for bladder stimulation in patients with bladder voiding dysfunctions. Brindley was the first researcher who succeeded in stimulating the spinal nerves via implanted electrodes in an animal model. In the years 1978/79 Brindley implanted five paraplegic patients with so-called sacral anterior root stimulators; all of them were able to void under stimulation. This method of sacral anterior root stimulation (SARS) proved an alternative to frequent one-way catheterisation for patients with severe voiding dysfunctions, without achieving complete continence, however. The following study is to provide an overview over the latest insights in the context of implanting sacral anterior root stimulators; it discusses the preconditions required for such interventions and presents criteria to decide in which cases there is a contraindication for sacral deafferentation of the posterior roots. Moreover, it contrasts advantages and disadvantages of the intradural and extradural implantation methods and presents the currently available long-term follow-up results with SDAF and SARS for treatment of bladder voiding dysfunctions.

[A suggested treatment algorithm in nocturnal enuresis with emphasis on partial responders]. / Therapiealgorithmus bei Enuresis nocturna.

Monotherapeutic strategies often have only partial success in primary nocturnal enuresis (PNE). This analysis evaluated whether adjuvant treatment strategies improve outcomes. PNE children were submitted to a distinct therapeutic strategy including urotherapy (behavioral modifications), a first-line and, if necessary, a second-line treatment period. Outcome was the relief of bedwetting, the follow-up was 3-79 months. Urotherapy was applied. Nonresponders were assigned to desmopressin as first-line treatment. For complete responders a structured withdrawal program was applied. Partial responders were assigned to adjuvant second-line treatment according to their individual symptomatology, masked at basic investigations, incorporating either anticholinergics (propiverine hydrochloride), biofeedback, alpha-blocker (alfuzosin), alarm or psychotherapy, in addition to desmopressin. Nonresponders were referred to specialized management. The study included 259 children suffering from PNE (92 girls, 167 boys, aged 5-18 years): 42 children were relieved from bedwetting after urotherapy and 136 children had a complete response to desmopressin. Three nonresponders were assigned to specialized management, 61 partial responders had adjuvant treatments, and 17 partial responders had no further treatment. The suggested treatment algorithm resulted in 227 complete responders, 29 partial responders, and 3 nonresponders. The need for preliminary urotherapy is evident. The proposed desmopressin monotherapeutic strategy, incorporating a structured withdrawal program, is more effective than the standard desmopressin treatment module. Applying adjuvant treatment modules improves the complete response rate up to 88%. In partial responders overall efficacy rates are improved further. Nonresponders (1.2%) will be referred to specialized management, but many partial responders will gain improvement sufficient to refrain from invasive procedures.

[Sacral neuromodulation in patients with nonobstructive, chronic urinary retention: relevance of the carbachol test and influence of associated nerve lession]. / Sakrale Neuromodulation bei nichtobstruktiver, chronischer Harnretention: Die Wertigkeit des Carbacholtests und der Einfluss der assoziierten Nervenläsion.

OBJECTIVE: Aim of this study was to evaluate whether the carbachol test and the nerve lesions responsible for bladder dysfunction possess predictive value in patients with chronic urinary retention who undergo temporary sacral neuromodulation (PNE test). MATERIAL AND METHODS: In 1999 and 2000, PNE tests were performed in 24 patients with chronic urinary retention and acontractile detrusor previously assessed by urodynamics. In 18 patients, a carbachol test was performed during urodynamics. The diagnosis related to the acontractile detrusor was additionally assessed and compared to the successful outcome of the PNE test. RESULTS: The PNE test was successful in 8 of the 24 patients (33.3 %). The bladder was completely emptied during the PNE test in 3 of the 10 patients with negative carbachol test and in 3 of the 8 patients with positive carbachol test. The highest success rate (80 %) was observed in patients after hysterectomy, whereas after lumbosacral pulposal prolapse or with a CNS tumor, it was only 20 - 33.3 %. CONCLUSIONS: We conclude that sacral neuromodulation is an effective treatment option in patients with nonobstructive urinary retention. The carbachol test does not possess any definitive predictive value with respect to the success rate of sacral neuromodulation in patients with chronic urinary retention. The success rate more likely depends on the localisation of the nerve lesion. PNE tests should be performed in all patients with therapy resistent nonobstructive urinary retention, as no other predictive factors exist.

[Clinical Results of PNE Tests in 70 Patients with Different Bladder Dysfunctions]. / Klinische Ergebnisse nach 70 bilateralen peripheren Nerven-Evaluationstests (PNE-Test) bei Patienten mit Harnblasendysfunktionen.

PURPOSE: Prior to implantation of a sacral neuromodulator we carried out PNE tests (peripheral nerve evaluation test) with bilateral test stimulation to establish which patients might profit from this kind of therapy. In contrast to the original unilateral technique used by Tanagho and Schmidt, we performed bilateral PNE test stimulation. Moreover, we analysed the diagnostic characteristics of those patients who had positive PNE test results and could thus receive a chronic sacral neuromodulator. MATERIALS AND METHODS: We performed bilateral PNE test stimulation in 70 patients (mean age: 53.6 yrs; 41 with retention symptoms and 29 with a hyperactive detrusor) over a minimum of 3 days. Retrospectively, we analysed the distribution of diagnostic characteristics (retention vs. overactive bladder and neurogenic vs. idiopathic) in the implant recipients. RESULTS: All patients received bilateral PNE test stimulation, during which the stimulation amplitudes were adjusted individually for each side. 8 patients were treated with the original PNE-electrode (model 0 041 830 - 002, Medtronic Inc., USA) without success. Of the remaining 62 patients, who were treated with an improved electrode, the PNE test was successful in 32 cases (51.6 %). Twenty-seven of these patients suffered from a neurogenic bladder dysfunction, and, in 5 cases, the causes were idiopathic. CONCLUSIONS: Bilateral PNE-test stimulation and the use of advanced PNE electrodes (model 3057, Medtronic Inc., USA) led to a positive PNE result in 51.6 % of the tested patients. Of these, the group with neurogenic bladder dysfunctions showed the highest response rate. Compared with the success rates in the multicenter study, we were able to increase the overall PNE response rate significantly. For this reason, we prefer a bilateral PNE-test with side-specific stimulation.

[Sacral neuromodulation in treatment of functional disorders of the lower urinary tract. An overview of basic principles, indications, outcomes]. / Sakrale Neuromodulation in der Behandlung von Funktionsstörungen des unteren Harntrakts. Ein Uberblick über Prinzip, Indikationen und Ergebnisse.

Over the last few years, sacral neuromodulation has become an established treatment option for dysfunctions of the lower urinary tract. It fills the gap that used to exist between conservative therapy and costly invasive methods such as urinary drainage via a deactivated bowel segment. Initially, the clinical value of sacral neuromodulation was controversial even among neurourologists. This was mainly due to a lack of understanding of the physiological processes, uncertain diagnostics, the design of the hardware, and a surgical topography relatively unknown to the urologist. In the meantime, however, sacral neuromodulation has become a standard part of clinical routine with respect to the treatment of dysfunctions of the lower urinary tract, and it is regularly employed in various urological institutions across Europe and the USA. This form of treatment, which is the final straw for patients who believed themselves-after many frustrated therapy attempts-to be "hopeless cases," can now also successfully be employed as an ambulatory measure. The latest data from our hospital, as well as contributions presented at the last DGU Congress in Wiesbaden, indicate that patients with neurogenic urinary retention are the most likely to profit from this treatment option.

Stimulation signal modification in a porcine model for suppression of unstable detrusor contractions.

OBJECTIVES: To investigate, in an experimental study, the efficacy of a different stimulation signal in a porcine model to suppress formalin-induced unstable detrusor contractions. The current mode of stimulation in peripheral nerve evaluation tests and sacral neuromodulation is based on rectangular signal shapes. Published reports, however, have revealed that up to 80% of patients do not respond to peripheral nerve evaluation stimulation. METHODS: After placement of electrodes at S3 in 12 anesthetized Göttinger minipigs, unstable contractions were induced by intravesical instillation of formalin. Ten-minute stimulation phases with a quasi-trapezoidal signal and a rectangular signal followed. An interval of 30 minutes elapsed between the two series of stimulations. The pressure values were registered on a urodynamic unit and evaluated as contractions and amplitudes per minute. Six minipigs were treated in the same way but were not stimulated and served as the control group. RESULTS: After formalin instillation, the average number of involuntary detrusor contractions was 3.5/min (+/- 0.8) and the sum of amplitudes was 7.2/min (+/- 1.1). Subsequent NaCl instillation and quasi-trapezoidal stimulation reduced the contractions to 0.3/min (+/- 0.3) and the sum of amplitudes to 0.8/min (+/- 0.4). A contraction rate of 1.1/min (+/- 0.1) and a sum of amplitudes of 5.1/min (+/- 2.4) were recorded under stimulation with a rectangular signal. In the control group, no significant reduction was recorded. CONCLUSIONS: The acquired data demonstrate that quasi-trapezoidal stimulation suppresses unstable detrusor contractions in the minipig more effectively than does conventional rectangular stimulation as presently applied in sacral neuromodulation.

Selective block of urethral sphincter contraction using a modified Brindley electrode in sacral anterior root stimulation of the dog.

AIMS: Patients with spinal cord injury often present with dysfunction of urinary bladder and urethral sphincter. One treatment option is sacral rhizotomy and sacral anterior root stimulation with the Finetech Brindley stimulator. However, a major disadvantage is the lack of selective stimulation, resulting in simultaneous contraction of sphincter and bladder followed by unphysiological micturition. This study investigated the possibility of selective bladder stimulation by using a Brindley electrode. METHODS: In 11 male anaesthetized foxhounds, a complete posterior rhizotomy was perormed. The anterior S2 roots were stimulated with different quasi-trapezoidal (QT) pulses (pulse length range, 600-1,400 microsec; stimulation current, 0.1-2.0 mA; frequency, 20 Hz) by using a tripolar Brindley electrode. Sphincter and bladder pressures were measured urodynamically. RESULTS: All 11 animals showed a maximal reduction of the highest sphincter pressure over 80%, and in 6 of 11 trials, the sphincter pressure was inhibited completely (100%). With stimulations at maximal sphincter blockade, the average achievable bladder pressure was 33.48 cm H(2)O higher than the average sphincter pressure, and in three cases, a strong micturition was observed. Selective blockade of the sphincter was possible by applying QT pulses. The bladders remained uninfluenced by this blockade and kept their excitability at any time. CONCLUSIONS: This study shows that selective bladder stimulation with little or no coactivation of the sphincter is possible. A physiological micturition can be achieved by using a tripolar Brindley electrode. Introduction of this stimulation technique into clinical practice should not face major difficulties, considering that the device is an established electrode.

[Chronic sacral bilateral neuromodulation. Using a minimal invasive implantation technique in patients with disorders of bladder function]. / Chronische sakrale bilaterale Neuromodulation. Einsatz einer minimalinvasiven Implantationstechnik bei Patienten mit Blasenfunktionsstörungen.

The implantable neuromodulation system described by Tanagho and Schmidt enables unilateral sacral nerve stimulation. Reports have been made on sacral neuromodulation failures of up to 50% in patients undergoing this procedure. We chose the bilateral electrode implantation and a minimal invasive laminectomy to ensure a more effective modulation and better placement and fixation of the electrodes. After successful assessment using a peripheral nerve evaluation test, 20 patients (14 with detrusor instability, 6 with hypocontractile detrusor) underwent minimally invasive laminectomy and bilateral electrode placement. In the patients with detrusor instability, the incontinence episodes were reduced from 7.2 to 1 per day and the bladder capacity improved from 198 to 352 ml. In patients with hypocontractile detrusor, the initial residual urine level of 450 ml dropped to 108 ml. Maximum detrusor pressure during micturition rose from 12 cmH2O initially to 34 cmH2O. The average follow up period was 17.5 months. There was no sign of deterioration in the modulation effect in any of the patients. Bilateral electrode implantation and the new sacral approach allow optimal neuromodulation in patients with bladder dysfunction. Laminectomy enables optimum electrode placement and fixation with minimal trauma.

[Volumetry of the urinary bladder with implantable ultrasound sensors]. / Volumetrie der Harnblase mittels implantierbaren Ultraschallsensoren.

Experimental studies revealed that the contractile response of the urinary bladder to sacral anterior root stimulation depends on the actual bladder volume. Furthermore, no clinical relevant technique is available for continuous monitoring of the bladder wall distension respectively bladder volume in paraplegic patients. The presented study investigates the reliability of especially developed implantable ultrasound sensors as a sensoric system for continuous monitoring of the bladder volume. In six anaesthesized pigs two ultrasound sensors, one transmitter and one receiver, were implanted on the bladder wall at different locations (latero-lateral, dorsal-ventral, rostral-caudal). After closing the abdominal wall, the bladder was filled in 50 ml steps up to 250 ml. After each filling step the running time of the ultrasound signal was measured. In all experiments reproducible results and a high correlation of the measured running times with bladder volume were observed. The latero-lateral configuration of the sensors seemed to be most confidential. The presented study indicates that bladder volumetry with implantable ultrasound sensors is possible with minimal technical prerequisites. This promising technique for continuous bladder volumetry could play an important role in the development of an intelligent and autoadaptive neurostimulator of the urinary bladder in paraplegic patients.

Restoration of bladder function in spastic neuropathic bladder using sacral deafferentation and different techniques of neurostimulation.

PURPOSE: Conventional sacral anterior root stimulation (SARS) results in simultaneous activation of both the detrusor muscle and the external urethral sphincter. We evaluated the possibilities of different neurostimulation techniques to overcome stimulation induced detrusor-sphincter-dyssynergia and to achieve a physiological voiding. MATERIAL AND METHODS: The literature was reviewed on different techniques of sacral anterior root stimulation of the bladder and the significance of posterior rhizotomy in patients with supraconal spinal cord injury suffering from the loss of voluntary bladder control, detrusor hyperreflexia and sphincter spasm. RESULTS: The achievement of selective detrusor activation would improve current sacral neurostimulation of the bladder, including the principle of "poststimulus voiding". This is possible with the application of selective neurostimulation in techniques of anodal block, high frequency block, depolarizing prepulses and cold block. Nowadays, sacral deafferentation is a standard therapy in combination with neurostimulation of the bladder because in conclusion advantages of complete rhizotomy predominate. CONCLUSIONS: The combination of sacral anterior root stimulation and sacral deafferentation is a successful procedure for restoration of bladder function in patients with supraconal spinal cord injury. Anodal block technique and cryotechnique are excellent methods for selective bladder activation to avoid detrusor-sphincter-dyssynergia and thus improve stimulation induced voiding.

[Neurotherapy of the hyperactive bladder]. / Neuraltherapie der hyperaktiven Blase.

Results in the treatment of non-neurogenic bladder hyperactivity are unsatisfactory. However, the first promising results from neurostimulation and our own findings in the neuroanatomy and neurophysiology of the lower urinary tract have led us to consider peripheral neurostimulation of the S2 - dorsal root or dorsal nerve of the penis for treating patients with hyperactive bladder dysfunction. We report on the first 14 cases treated by peripheral neurostimulation and S2-dorsal root blockade with local anesthesia for bladder hyperactivity. The bladder function became normal, and the bladder capacity increased up to 400% under neurotherapy. The methods, results and complications are discussed.