Ulrich Mehnert

The Effect of Botulinum Toxin Type A on Overactive Bladder Symptoms in Patients With Multiple Sclerosis: A Pilot Study

PURPOSE Patients with multiple sclerosis often experience overactive bladder symptoms. High dose intradetrusor botulinum toxin A treatment is effective but often results in urinary retention and urinary diversion via a catheter. In this pilot study we evaluated whether only 100 U botulinum toxin A would significantly decrease overactive bladder symptoms in patients with multiple sclerosis without impairing pretreatment voluntary voiding. MATERIALS AND METHODS Included in our study were 12 patients with multiple sclerosis who had overactive bladder symptoms such as urgency, frequency and/or urgency incontinence. The treatment effect was evaluated using data on 3 consecutive visits, that is before, and a mean +/- SD of 46.2 +/- 11.9 and 101 +/- 21 days after intradetrusor injection of 100 U Botox, including the results of cystometry and uroflowmetry at visits 1 and 2, and uroflowmetry alone at visit 3. Patients completed a 3-day voiding diary for all 3 visits. RESULTS Maximum bladder capacity significantly increased and maximum detrusor pressure decreased. Daytime and nighttime frequency, urgency and pad use significantly decreased. Post-void residual volume significantly increased initially but decreased until 12 weeks. Median time to re-injection due to recurrent overactive bladder symptoms was 8 months. CONCLUSIONS Overactive bladder treatment in patients with multiple sclerosis using 100 U Botox intradetrusor injections seems to be effective and safe. Despite slightly impaired detrusor contractility most patients still voided voluntarily without symptoms. Thus, 100 U Botox may be a reasonable treatment option for overactive bladder symptoms in patients with multiple sclerosis who still void voluntarily.

Brain activation in response to bladder filling and simultaneous stimulation of the dorsal clitoral nerve—An fMRI study in healthy women

AIMS Using functional magnetic resonance imaging (fMRI) we investigated the cortical and subcortical representations during bladder filling and the effect of simultaneous stimulation of the dorsal clitoral nerve on these cortical and subcortical structures. METHODS After approval of the local ethics committee, 8 healthy females were included. Prior to scanning, subjects were catheterized and the bladder was filled until first desire to void occurred. In a block design protocol we performed repetitive manual bladder filling (FILLING) and emptying of additional 80 ml saline, alternating with rest conditions (REST) of constant bladder volume. The protocol was repeated with simultaneous stimulation of the dorsal clitoral nerve during the filling periods (COMBINED). Activation maps were calculated by means for 3 different contrasts: 1) FILLING>REST, 2) COMBINED>REST and 3) FILLING>COMBINED. RESULTS A group analysis of contrast 1) showed activation of the right prefrontal and orbitofrontal cortices, the insula bilaterally, the left precuneus, the parietal operculum bilaterally, the cerebellum bilaterally (q(FDR)< or =0.001), the right anterior cingulate gyrus (q(FDR)< or =0.005) and the right anterior mid pons (q(FDR)< or =0.05). Contrast 2) showed activation in the right frontal area, the left insula, the parietal operculum bilaterally and the left cerebellum (q(FDR)< or =0.001). Deactivations were found in the middle frontal gyrus bilaterally and the post- and paracentral gyri bilaterally. Contrast 3) revealed stronger activation during FILLING in the bilateral frontal and prefrontal areas, the right anterior cingulated gyrus, and the right putamen (q(FDR)< or =0.05). Only the right insula showed stronger activation during the COMBINED condition. CONCLUSION Simultaneous dorsal clitoral nerve stimulation during bladder filling reduced the activation of certain cortical areas suggesting a neuromodulatory effect of this stimulation on supraspinal centres involved in lower urinary tract control.

Treatment of Neurogenic Stress Urinary Incontinence Using an Adjustable Continence Device: 4-Year Followup

PURPOSE We evaluated the long-term safety and efficacy of an adjustable continence device (ACT® or ProACT™) in male and female patients with neurogenic stress urinary incontinence. MATERIALS AND METHODS Data on patients consecutively treated with implantation of an adjustable continence device due to neurogenic stress urinary incontinence were reviewed from the start of our experience to the current 4-year followup. RESULTS We reviewed data on 13 male and 24 female patients with neurogenic stress urinary incontinence due to different forms of pelvic nerve or spinal cord lesions. Mean ± SD age at implantation was 46.2 ± 17.4 years. Of the patients 92% performed clean intermittent self-catheterization. The device was implanted bilaterally using general and local anesthesia in 16.2% and 83.8% of cases, respectively. From before implantation to 48-month followup the mean number of urinary incontinence episodes decreased from 6.1 ± 2.4 to 2.8 ± 3.1 and the mean number of pads used per 24 hours decreased from 4.2 ± 2.7 to 2.2 ± 2.2. Of the patients 54.5% indicated more than 50% improvement of stress urinary incontinence symptoms after 48 months, of whom 38.9% indicated complete continence. Adverse events included erosion/migration, device infection or failure, implantation site pain, bladder stone formation and difficult clean intermittent self-catheterization. CONCLUSIONS Implantation of the ProACT/ACT device in patients with neurogenic stress urinary incontinence is minimally invasive and safe. It can significantly improve neurogenic stress urinary incontinence in the long term. Thus, it might be a reasonable option for patients who are not willing, not suitable or not yet ready for more invasive surgery, such as artificial urinary sphincter or fascial suspension sling placement.

Differential functional brain network connectivity during visceral interoception as revealed by independent component analysis of fMRI TIME-series.

Influential theories of brain‐viscera interactions propose a central role for interoception in basic motivational and affective feeling states. Recent neuroimaging studies have underlined the insula, anterior cingulate, and ventral prefrontal cortices as the neural correlates of interoception. However, the relationships between these distributed brain regions remain unclear. In this study, we used spatial independent component analysis (ICA) and functional network connectivity (FNC) approaches to investigate time course correlations across the brain regions during visceral interoception. Functional magnetic resonance imaging (fMRI) was performed in thirteen healthy females who underwent viscerosensory stimulation of bladder as a representative internal organ at different prefill levels, i.e., no prefill, low prefill (100 ml saline), and high prefill (individually adapted to the sensations of persistent strong desire to void), and with different infusion temperatures, i.e., body warm (∼37°C) or ice cold (4–8°C) saline solution. During Increased distention pressure on the viscera, the insula, striatum, anterior cingulate, ventromedial prefrontal cortex, amygdalo‐hippocampus, thalamus, brainstem, and cerebellar components showed increased activation. A second group of components encompassing the insula and anterior cingulate, dorsolateral prefrontal and posterior parietal cortices and temporal‐parietal junction showed increased activity with innocuous temperature stimulation of bladder mucosa. Significant differences in the FNC were found between the insula and amygdalo‐hippocampus, the insula and ventromedial prefrontal cortex, and the ventromedial prefrontal cortex and temporal‐parietal junction as the distention pressure on the viscera increased. These results provide new insight into the supraspinal processing of visceral interoception originating from an internal organ. Hum Brain Mapp 36:4438–4468, 2015.

The effects of tolterodine on bladder-filling sensations and perception thresholds to intravesical electrical stimulation : method and initial results

To study the effects of the antimuscarinic agent tolterodine on the perception thresholds to intravesical electrical stimulation (IES) and the effects of the drug on subjective bladder sensation during normal filling cystometry in healthy female volunteers.

Neurogenic lower urinary tract dysfunction (NLUTD) in patients with spinal cord injury: long-term urodynamic findings

To investigate long‐term urodynamic findings in patients with spinal cord injury (SCI) with neurogenic lower urinary tract dysfunction (NLUTD).

Acute Spinal Cord Injury—Do Ambulatory Patients Need Urodynamic Investigations?

PURPOSE We compared the urodynamic parameters of ambulatory vs nonambulatory acute spinal cord injured patients. MATERIALS AND METHODS A total of 27 women and 33 men (mean age 58 years) with neurogenic lower urinary tract dysfunction due to acute spinal cord injury (duration of injury less than 40 days) were prospectively evaluated. The patients were dichotomized according to the mobility for moderate distances subscale of the SCIM (Spinal Cord Independence Measure) version III into ambulatory (score of 3 or greater) and nonambulatory (score less than 3). Videourodynamic parameters including maximum detrusor pressure during the storage phase, bladder compliance, detrusor overactivity, detrusor external sphincter dyssynergia and vesicoureterorenal reflux were compared between the groups. RESULTS Of the 60 patients with acute spinal cord injury 17 were ambulatory and 43 were nonambulatory. Mean ± SD duration of injury at urodynamic investigation was 30 ± 8 days. The lesion level was cervical in 14 patients, thoracic in 28 and lumbar/sacral in 18. Comparing unfavorable urodynamic parameters, no significant differences were found between ambulatory vs nonambulatory patients in terms of a high pressure system during the storage phase (29% vs 33%, p = 0.81), a low compliance bladder (12% vs 7%, p = 0.54), detrusor overactivity (24% vs 47%, p = 0.1), detrusor external sphincter dyssynergia (18% vs 21%, p = 0.77) and vesicoureterorenal reflux (0% vs 5%, p = 0.36). CONCLUSIONS Ambulatory and nonambulatory patients with acute spinal cord injury have a similar risk of unfavorable urodynamic measures. Thus, we strongly recommend the same neurourological assessment including urodynamic investigations in all acute spinal cord injury patients independent of the ability to walk.

Neurogenic Lower Urinary Tract Dysfunction—Do We Need Same Session Repeat Urodynamic Investigations?

PURPOSE We investigated whether same session repeat urodynamic investigations are needed in patients with neurogenic lower urinary tract dysfunction. MATERIALS AND METHODS A consecutive series of 226 patients with neurogenic lower urinary tract dysfunction who underwent same session repeat urodynamic investigation was prospectively investigated at a single university spinal cord injury center. Urodynamics were done according to the good urodynamic practices recommended by the International Continence Society. All 226 patients underwent same session repeat consecutive filling cystometry and 88 also underwent pressure flow studies if they could void spontaneously. Repeatability of the 2 measurements was assessed using the Bland and Altman 95% limits of agreement, and the κ statistic. RESULTS Mean age of the 226 patients enrolled was 52 years (range 18 to 90). Of the patients 94 (42%) were women and 132 were (58%) men. Detrusor overactivity repeatability was excellent between the 2 urodynamic investigations (κ=0.87, 95% CI 0.80-0.94). For all other urodynamic parameters assessed there were wide 95% limits of agreement for differences in the parameters, indicating poor repeatability. CONCLUSIONS In same session repeat urodynamic investigations of patients with neurogenic lower urinary tract dysfunction detrusor overactivity demonstrates excellent repeatability but all other urodynamic parameters show insufficient agreement. Thus, we strongly recommend that clinical decision making not be based on a single urodynamic investigation since repeat measurements may yield completely different results.

Bacteriophages as Potential Treatment for Urinary Tract Infections.

Background: Urinary tract infections (UTIs) are among the most prevalent microbial diseases and their financial burden on society is substantial. The continuing increase of antibiotic resistance worldwide is alarming so that well-tolerated, highly effective therapeutic alternatives are urgently needed. Objective: To investigate the effect of bacteriophages on Escherichia coli and Klebsiella pneumoniae strains isolated from the urine of patients suffering from UTIs. Material and methods: Forty-one E. coli and 9 K. pneumoniae strains, isolated from the urine of patients suffering from UTIs, were tested in vitro for their susceptibility toward bacteriophages. The bacteriophages originated from either commercially available bacteriophage cocktails registered in Georgia or from the bacteriophage collection of the George Eliava Institute of Bacteriophage, Microbiology and Virology. In vitro screening of bacterial strains was performed by use of the spot-test method. The experiments were implemented three times by different groups of scientists. Results: The lytic activity of the commercial bacteriophage cocktails on the 41 E. coli strains varied between 66% (Pyo bacteriophage) and 93% (Enko bacteriophage). After bacteriophage adaptation of the Pyo bacteriophage cocktail, its lytic activity was increased from 66 to 93% and only one E. coli strain remained resistant. One bacteriophage of the Eliava collection could lyse all 9 K. pneumoniae strains. Conclusions: Based on the high lytic activity and the potential of resistance optimization by direct adaption of bacteriophages as reported in this study, and in view of the continuing increase of antibiotic resistance worldwide, bacteriophage therapy is a promising treatment option for UTIs highly warranting randomized controlled trials.

Supraspinal Control of Urine Storage and Micturition in Men—An fMRI Study

Despite the crucial role of the brain in the control of the human lower urinary tract, little is known about the supraspinal mechanisms regulating micturition. To investigate the central regulatory mechanisms activated during micturition initiation and actual micturition, we used an alternating sequence of micturition imitation/imagination, micturition initiation, and actual micturition in 22 healthy males undergoing functional magnetic resonance imaging. Subjects able to micturate (voiders) showed the most prominent supraspinal activity during the final phase of micturition initiation whereas actual micturition was associated with significantly less such activity. Initiation of micturition in voiders induced significant activity in the brainstem (periaqueductal gray, pons), insula, thalamus, prefrontal cortex, parietal operculum and cingulate cortex with significant functional connectivity between the forebrain and parietal operculum. Subjects unable to micturate (nonvoiders) showed less robust activation during initiation of micturition, with activity in the forebrain and brainstem particularly lacking. Our findings suggest that micturition is controlled by a specific supraspinal network which is essential for the voluntary initiation of micturition. Once this network triggers the bulbospinal micturition reflex via brainstem centers, micturition continues automatically without further supraspinal input. Unsuccessful micturition is characterized by a failure to activate the periaqueductal gray and pons during initiation.