Treatment outcomes and resource use of patients with neurogenic detrusor overactivity receiving botulinum toxin A (BOTOX) therapy in Germany.

PURPOSE: To evaluate treatment outcomes and resource consumption of patients with neurogenic detrusor overactivity (NDO) before and after botulinum toxin A (Botox) therapy in Germany. METHODS: In a multi-center, cross-sectional, retrospective cohort study, data of patients with NDO 12 months before and after the first Botox therapy were analyzed. RESULTS: 214 patients (mean age 38 +/- 14.8 years, 145 male, 69 female) with NDO due to spinal cord injury (81%); myelomeningocele (14%), or Multiple Sclerosis (5%) from seven hospitals were included. Mean interval between treatments was 8 months. Following treatment, mean maximum detrusor pressure, maximum cystometric capacity and detrusor compliance improved significantly. Prior to Botox therapy, 68% reported urinary tract infections (UTI), 63% had incontinence episodes, and 58% used incontinence aids. These numbers decreased significantly (p < 0.05) after treatment to 28, 33, and 28%, respectively. In patients using incontinence aids, mean costs per patient decreased from 2euro to 1euro per day, whereas the mean cost of drugs to treat UTIs per patient decreased from 163euro to 80euro per year, respectively. CONCLUSION: This is the first study demonstrating the clinical usefulness of Botox therapy in clinical practice. Successful treatment resulted in lower costs for NDO associated morbidity due to less need for incontinence aids and UTI medication.

Urodynamic changes and response rates in patients treated with permanent electrodes compared to conventional wire electrodes in the peripheral nerve evaluation test.

OBJECTIVES: Sacral neuromodulation having become established as an essentially effective new therapeutic modality, both in patients with anticholinergic-therapy refractory overactive bladder (OAB) and with chronic urinary retention. It is important to establish which patients might profit from this kind of therapy in order to ensure, by means of a peripheral nerve evaluation (PNE) test, that the implantation of a permanent stimulating device is effective. In a retrospective study we compared the urodynamic outcome of two different techniques (implantation of the permanent neurostimulation electrodes so-called "two-stage-implantation" vs. conventional PNE). METHODS: We performed a sacral nerve stimulation in 53 patients (30 urinary retention, 23 OAB syndrome). In 42 patients, we performed a conventional PNE, 11 patients received "two-stage-implantation" with implantation of the permanent electrodes. RESULTS: In 20 cases the conventional PNE-test (cPNE) was successful (47.6% of all cPNE). The response rate of "two-stage-implantation" (permanent electrodes) was 81.8%. In patients with overactive bladder the bladder capacity was increased by 30% with cPNE (P = 0.068) versus 52% when permanent electrodes were used (P = 0.017). Bladder instabilities were reduced by ca. 75%. In urinary retention, the cPNE versus permanent electrodes led to an increase of the maximum detrusor pressure by 68 versus 94% with reduction of residual urine by 71% (P = 0.068) versus 66% (P = 0.042). CONCLUSIONS: The results of this study show that application of permanent quadripolar electrodes during PNE prior to chronic neuromodulator implantation leads to significantly higher responder rates and enables more efficient patient selection.

Improved sensory gating of urinary bladder afferents in Parkinson's disease following subthalamic stimulation.

In addition to motor symptoms, patients with Parkinson's disease (PD) show deficits in sensory processing. These deficits are thought to result from deficient gating of sensory information due to basal ganglia dysfunction in PD. Deep brain stimulation of the subthalamic nucleus (STN-DBS) has been shown to improve sensory deficits in PD, e.g. STN-DBS normalizes the perception of urinary bladder filling in patients with PD. This study aimed at investigating how STN-DBS modulates the processing of urinary bladder information to elucidate the (patho-)physiology of sensory gating mechanisms in PD. Nine PD patients with bilateral STN-DBS switched on (STN-DBS ON) or off (STN-DBS OFF) were studied during dynamic bladder filling and an empty bladder condition (for control), while changes in regional cerebral blood flow (rCBF) were measured by PET. Urinary bladder filling led to an increased rCBF in the periaqueductal grey (PAG), the posterior thalamus, the insular cortex as well as in the right frontal cortex and the cerebellum bilaterally. A significant interaction between bladder condition and STN-DBS was observed in the posterior thalamus and the insular cortex, with enhanced modulation of these areas during STN-DBS ON compared to STN-DBS OFF. Furthermore, regression analyses revealed a modulation of the neural activity in the thalamus and the insular cortex by the PAG activity during STN-DBS ON only. Thus, STN-DBS led to a significant enhancement of afferent urinary bladder information processing. The data suggest that STN-DBS facilitates the discrimination of different bodily states by supporting sensory perception and the underlying neural mechanisms. Furthermore, this is the first imaging study, which shows an effect of STN-DBS on sensory gating in PD patients and its neural basis.

Subthalamic stimulation modulates cortical control of urinary bladder in Parkinson's disease.

Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective therapy for off-period motor symptoms and dyskinesias in advanced Parkinson's disease. Clinical studies have shown that STN-DBS also ameliorates urinary bladder function in Parkinson's disease patients by delaying the first desire to void and increasing bladder capacity. This study aimed at investigating the effect of STN-DBS on the neural mechanisms underlying cerebral bladder control. Using PET to measure changes in regional cerebral blood flow (rCBF), 11 patients with bilateral STN-DBS were studied during urodynamic bladder filling in STN-DBS ON and OFF condition. A filled bladder led to a significant increase of rCBF in the anterior cingulate cortex, which was further enhanced during STN-DBS OFF. A significant interaction between bladder state and STN-DBS was observed in lateral frontal cortex with increased rCBF when the bladder was filled during STN-DBS OFF. The data suggest that STN-DBS ameliorates bladder dysfunction and that this modulation may result from facilitated processing of afferent bladder information.

Systemic nitric oxide augmentation leads to a rapid decrease of the bladder outlet resistance in healthy men.

OBJECTIVE: We examined the immediate effect of a systemic nitric oxide augmentation on the bladder outlet resistance in healthy men. METHODS: Eleven healthy male volunteers with a mean age of 25.5 yr were included in the study. They were prepared for a standard urodynamic study, and a baseline pressure-flow study was obtained. The subjects were then given 20 mg isosorbide dinitrate sublingually, and after refilling their bladder a second pressure-flow study was done after 20 min. The pressure-flow studies were then compared in regard to the average flow rate, the average detrusor pressure during micturition, and the detrusor pressure at maximum flow rate. RESULTS: One of the subjects was unable to void and had to be excluded from the study. In the remaining 10 men, the mean average flow rate increased from 16.7 ml/s before to 20.2 ml/s after the intake of the NO donor (P=0.013). Concomitantly, the average detrusor pressure during micturition decreased from a mean of 57 to 52 cm H2O (P=0.004) and the mean detrusor pressure at maximum flow rate decreased from 60 to 52 cm H2O (P=0.013). CONCLUSIONS: Systemic NO augmentation can lower the functional bladder outlet resistance very rapidly in men. Our results support the concept that the NO-cGMP pathway may be a promising target for medical treatment of lower urinary tract symptoms.

Systemic augmentation of nitric oxide: is there an immediate effect on the urinary flow rate in healthy men?

INTRODUCTION: Nitric oxide (NO) is an important neurotransmitter in the lower urinary tract. Data from experimental studies in animals and humans suggest that NO donors like isosorbide dinitrate could be used to lower the infravesical resistance. Despite the potentially significant clinical benefit of such an effect, it has hardly been studied in vivo in men. We investigated the immediate effect of isosorbide dinitrate on the urinary flow rate and the functional bladder capacity in healthy young men. PATIENTS AND METHODS: A free urinary flow was measured in 20 healthy male volunteers on two consecutive micturitions. 15-25 min prior to the second micturition, 10 mg of the NO donor isosorbide dinitrate was administered sublingually. RESULTS: We found no significant difference between baseline measurement and the micturition after NO administration with regard to the totally voided volume, the maximal or the average flow rate as well as the flow rate corrected for the voided volume. CONCLUSION: Systemic augmentation of NO does not produce a relevant immediate effect on the urinary flow rate or the functional bladder capacity in healthy men.

Understanding detrusor sphincter dyssynergia--significance of chronology.

OBJECTIVES: To evaluate in patients with spinal cord injury (SCI) and detrusor sphincter dyssynergia (DSD) whether the onset of external urethral sphincter (EUS) contractions precedes or follows the onset of bladder contractions and to address the issue of potential therapeutic approaches based on the understanding of DSD chronology. METHODS: A retrospective review of video-urodynamic recordings of patients with SCI that demonstrated both untreated neurogenic overactive bladder and DSD, from January 2002 to December 2003, was performed. Delay A was defined as the period between the onset of an EUS pressure increase and the onset of a bladder pressure increase and delay B as the period between the onset of a urethral sphincter pressure increase and the moment at which the bladder pressure increase reached 10 cm H2O greater than the baseline value. RESULTS: Twenty patients with traumatic SCI matched all inclusion criteria. Delay A was positive (EUS contracted first) in 16 (80%) of 20 patients. The mean time for delay A was 2.2 seconds. A positive association was found among a positive delay A, the completeness of the spinal lesion, and continuous DSD type. Delay B was positive in all 20 patients (100%). The mean time for delay B was 7.6 seconds. CONCLUSIONS: In most patients with SCI and DSD, the EUS contraction started before the onset of the bladder contraction. Additionally, in all patients with SCI, the EUS contraction started before the critical part of the bladder contraction. A pathophysiologic hypothesis for such chronology is discussed. A potential therapeutic application would be to use urethral sphincter activity to trigger inhibition of bladder contractions (conditional neuromodulation) and treat the neurogenic overactive bladder.

The effect of tamsulosin on the resting tone and the contractile behaviour of the female urethra: a functional urodynamic study in healthy women.

AIMS: The aim of this functional urodynamic experiment was to study the effect of the selective alpha1(A)-blocker tamsulosin on the urethral pressure in healthy human females and assessed first the resting urethral pressure and second the urethral contractility in response to magnetic stimulation of the sacral roots. METHODS: 11 healthy female subjects gave their written informed consent and were included. A microtip pressure transducer catheter was inserted into the bladder and three baseline urethral pressure profiles were obtained. Another three urethral pressure profiles were recorded while magnetic single pulse stimulation of the sacral roots was performed above the motor threshold of the pelvic floor to evoke reproducible urethral contractions. Then the subjects received 0.4 mg of tamsulosin and the entire protocol was repeated 6 hours after drug administration. Cardiovascular monitoring was obtained during the baseline and follow-up measurements. Mean and maximal urethral pressure values calculated over the entire urethra, mean pressure values calculated over the proximal, middle and distal third of the urethra and the pressure amplitudes to magnetic stimulation at baseline were statistically compared to the follow-up measurements with tamsulosin. RESULTS: The oral administration of tamsulosin did not change the systemic blood pressure, but did significantly reduce the mean and maximal urethral pressure acquired over the entire urethra. When the proximal, middle and distal third of the urethra were analysed separately, there was a significant pressure reduction in all three segments. Amplitudes of the urethral contractions evoked by sacral magnetic stimulation remained unchanged after tamsulosin. CONCLUSIONS: These data show a significant relaxing effect of tamsulosin on the resting urethral tone in healthy females in vivo. These results may suggest tamsulosin as a new pharmacological approach to treat urinary retention due to overactive or non-relaxing urethra in women.

The effect of nitric oxide on the resting tone and the contractile behaviour of the external urethral sphincter: a functional urodynamic study in healthy humans.

AIMS: This functional urodynamic study assessed the effect of the nitric oxide donor isosorbide dinitrate on the external urethral sphincter and hypothesised first that nitric oxide could lower the resting sphincter pressure, second that nitric oxide could influence the sphincter contractility during magnetic stimulation, and third that nitric oxide could induce a faster external urethral sphincter fatigue during continuous magnetic stimulation. METHODS: Eight healthy males gave their written informed consent and were included. A 2-channel microtip pressure transducer catheter was inserted into the urethra measuring the bladder and the external urethral sphincter pressure. Magnetic stimulation of the sacral roots was performed to evoke reproducible contractions of the external urethral sphincter. The baseline protocol included six single pulse stimulations and three stimulations 10sec in duration each for two frequencies 5Hz and 50Hz with intensities at the motor threshold of the pelvic floor. Then the subjects received 10 mg of isosorbide nitrate sublingually and the protocol was repeated 5min, 20min, 40min and 60min after drug administration. RESULTS: The sublingual administration of isosorbide dinitrate could significantly reduce the resting pressure of the external urethral sphincter for at least one hour. The maximal contractile strength measured as the maximal urethral pressure during single pulse and continuous magnetic stimulation of the sacral roots also decreased significantly. Nitric oxide did not induce a significantly faster fatigue of the external urethral sphincter during continuous magnetic stimulation of the sacral roots. CONCLUSIONS: This study shows a functionally relevant effect of nitric oxide on the resting tone and the contractile behaviour of the human external urethral sphincter in vivo while the fatigue properties did not changed significantly. Nitric oxide donors could offer a new pharmacological approach to treat urinary retention due to overactive or non-relaxing external urethral sphincter.