André Reitz

Experience With 100 Cases Treated With Botulinum-A Toxin Injections in the Detrusor Muscle for Idiopathic Overactive Bladder Syndrome Refractory to Anticholinergics

PURPOSE In this prospective, nonrandomized, ongoing study we evaluated the efficacy and safety of botulinum-A toxin injections in the detrusor muscle to treat patients with idiopathic overactive bladder resistant to conventional treatment, such as anticholinergic drugs. MATERIALS AND METHODS A total of 23 men and 77 women with a mean age of 63 years (range 24 to 89) with nonneurogenic overactive bladder, including urgency-frequency syndrome, and incontinence despite the administration of maximal doses of anticholinergics were consecutively treated with injections of 100 U botulinum-A toxin in the detrusor muscle at 30 sites under cystoscopic guidance. Micturition diary, full urodynamics, neurological status and urine probes were performed in all participants before treatment. Bladder biopsies were done only in cases of suspected bladder fibrosis or unclear findings. Special attention was given to reflex volume, maximal bladder capacity, detrusor compliance, post-void residual urine, urgency and frequency/nocturia. Clinical, urodynamic and quality of life assessments were performed at baseline, and 4, 12 and 36 weeks after botulinum-A toxin treatment. RESULTS Overall after 4 and 12 weeks 88% of our patients showed significant improvement in bladder function in regard to subjective symptoms, quality of life and urodynamic parameters (p <0.001). Urgency disappeared in 82% of the patients and incontinence resolved in 86% within 1 to 2 weeks after botulinum-A toxin injections. Mean frequency decreased from 14 to 7 micturitions daily (-50%) and nocturia decreased from 4 to 1.5 micturitions. Mean maximal bladder capacity increased 56% from 246 to 381 ml, mean detrusor compliance increased from 24 to 41 ml/cm H(2)O and pretreatment detrusor instability (mean reflex volume 169 ml) resolved in 74% of patients. Mean volume at first desire to void increased from 126 to 212 ml and mean urge volume increased from 214 to 309 ml. There were no severe side effects except temporary urine retention in 4 cases. Only in 8 patients was the clinical benefit poor and analysis revealed preoperative low detrusor compliance. Mean efficacy duration +/- SD was at least approximately 6 +/- 2 months and then symptoms began to increase. CONCLUSIONS Our results show that intradetrusor botulinum-A toxin injections may be an efficient and safe treatment option in patients with severe overactive bladder resistant to all conventional treatments.

An fMRI study of the role of suprapontine brain structures in the voluntary voiding control induced by pelvic floor contraction.

We have learned that micturition is comprised of two basic phases: storage and emptying; during bladder emptying, the pontine and periaqueductal gray (PAG) micturition center ensures coordinated inhibition of striated sphincter and pelvic floor muscles and relaxation of the internal urethral sphincter while the detrusor muscle contracts. Due to several disorders of the brain and spinal cord, the achieved voluntary control of bladder function can be impaired, and involuntary mechanisms of bladder activation again become evident. However, little has been discovered so far how higher brain centers strictly regulate the intricate process of micturition. The present functional magnetic resonance imaging (fMRI) study attempted to identify brain areas involved in such voluntary control of the micturition reflex by performing functional magnetic resonance imaging during a block design experiment in 12 healthy subjects. The protocol consisted of alternating periods of rest and pelvic muscle contraction during empty-bladder condition (EBC) and full-bladder condition (FBC). Repeated pelvic floor muscle contractions were performed during full bladder to induce a stronger contrast of bladder sensation, desire to void and inhibition of the micturition reflex triggering, since the subjects were asked not to urinate. Empty-bladder conditions were applied as control groups. Activation maps calculated by contrast of subtracting the two different conditions were purposed to disclose these brain areas that are involved during the inhibition of the micturition reflex, in which contrast, the SMA, bilateral putamen, right parietal cortex, right limbic system, and right cerebellum were found activated. The combined activation of basal ganglia, parietal cortex, limbic system, and cerebellum might support the assumption that a complex visceral sensory-motor program is involved during the inhibitory control of the micturition reflex.

Impact of spinal cord injury on sexual health and quality of life

To provide a comprehensive insight into sexuality after spinal cord injury, 120 patients received a questionnaire to assess their sexual activities, abilities, desires, satisfaction and sexual adjustment after injury. In the 63 responding patients, spinal cord injury had a major impact on sexual function. Relationship to partner, social life, bladder management and physical well-being had a significant impact on quality of life. Relationship to partner, ability to move and mental well-being, as well as aspects of sexual desire and body image had a significant correlation to satisfaction with sexual life. In the studied population, there was no significant correlation between preserved sexual abilities after spinal cord injury and the satisfaction with sexual life.

Intravesical therapy options for neurogenic detrusor overactivity

Study design: Review article.Setting: Neuro-Urology, Spinal Cord Injury Center, Balgrist University Hospital, Zurich, Switzerland.Objectives: This review considers intravesical treatment options of neurogenic detrusor overactivity and discusses the underlying mechanism of action, clinical safety and efficacy, and the future trends.Methods: The available literature was reviewed using medline services.Results: Oral anticholinergic drugs are widely used to treat detrusor overactivity, but they are ineffective in some patients or cause systemic side effects such as blurred vision or dry mouth. As an alternative, topical therapy strategies have been suggested to achieve a profound inhibition of the overactive detrusor and to avoid high systemic drug levels. Currently available intravesical treatment options either act on the afferent arc of the reflex such as local anaesthetics or vanilloids or on the efferent cholinergic transmission to the detrusor muscle such as intravesical oxybutynin or botulinum toxin. Although an established and effective therapy, intravesical oxybutynin is not widely used. Evidence for clinical significance of intravesical atropine and local anaesthetic is missing. Intravesical capsaicin has been shown to improve clinical and urodynamic parameters, but cause pain in some patients. The intravesical instillation of resiniferatoxin and the injection of botulinum-A toxin into the detrusor muscle are promising new options; however, randomised placebo-controlled studies to prove their safety and efficacy are still missing.Conclusion: Intravesical treatment strategies in patients with neurogenic detrusor overactivity may provide alternatives to established therapies such as oral anticholinergics. The selectivity of the intravesical treatment and the reduction or even the absence of side effects are major advantages of this topical approach.

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.

Sympathetic sudomotor skin activity in human after complete spinal cord injury

Spinal cord injury (SCI) causes serious disturbances in autonomic innervation and malfunction of the sympathetic nervous system that controls the pelvic organs, blood pressure, skin temperature and sweating. We studied sympathetic sudomotor pathways in 6 healthy subjects and 14 patients with sensory and motor complete SCI on cervical, thoracic and lumbar level. Sympathetic skin responses (SSRs) were provoked by auditory bursts and electrical stimulation of median, pudendal and tibial nerve and recorded from the palmar and plantar skin. The SSRs in healthy subjects occurred generally with the same pattern and with similar latencies suggesting a common sudomotor pathway mediating the SSR. Appearance or absence of the SSRs in SCI following stimulation above the lesion depend on the spinal level of lesion and on the location of stimulation. Lesions below T3 show palmar and lesions below T12 palmar and plantar SSR. Pudendal nerve stimulation evoked plantar SSRs in patients with complete cervical and thoracic SCI. No SSRs were obtained in patients with lesions at L1 and more caudal. SSRs following pudendal nerve stimulation in complete SCI above the level L1 are mediated by sacral somatic afferents and a sympathetic pathway originating at the upper lumbar level. The underlying sacro-lumbar reflex circuit is organized on spinal level and requires intact lumbar segments. Tibial nerve stimulation was not found to elicit SSRs below a SCI lesion and we suppose that this type of electrical stimulation cannot activate the spinal sudomotor reflex circuit.

Electrophysiological Assessment of Sensations Arising from the Bladder: Are there Objective Criteria for Subjective Perceptions?

PURPOSE Initial bladder filling sensation, first and strong desire to void are subjective perceptions that occur periodically during the urine storage mode of bladder function, representing sensory input from the lower urinary tract. To our knowledge methods for evaluating sensory bladder function are not available. We studied a simple electrophysiological procedure for the objective assessment of bladder sensations using sympathetic skin responses and surface pelvic floor electromyography. MATERIALS AND METHODS Informed consent was provided by 8 healthy male subjects, who were administered 20 mg. furosemide and 1 l. fluid to drink. Palmar and plantar sympathetic skin responses, and surface pelvic floor electromyogram were continuously recorded during bladder filling, voluntary pelvic floor contraction and voiding. RESULTS First desire to void evoked simultaneous sympathetic skin responses and pelvic floor contractions. This pattern appeared periodically with the desire to void sensation as well as with strong desire to void at maximum bladder capacity and it correlated well with the subjective sensation of the subjects. Voluntary pelvic floor contraction decreased the subjective intensity of the desire to void sensation as well as sympathetic skin response activity for the same short period. During voiding sympathetic skin responses almost complete absence of sympathetic skin responses was observed. CONCLUSIONS Sensations arising from the bladder induce combined activation of sympathetic skin responses and pelvic floor activity. This coherence indicates synchronized activation and inactivation of the autonomic and somatic pathways necessary for appropriate urine storage and coordinated voiding. Our observations may introduce a new approach for objectively assessing subjective sensations arising from the urinary tract.

Electromotive drug administration of lidocaine to anesthetize the bladder before botulinum-A toxin injections into the detrusor

Study design: Prospective, open label, cross-over-designed clinical study.Objective: To evaluate the effectiveness of an instillation of lidocaine into the bladder with versus without electromotive drug administration (EMDA) to anesthetize the bladder before botulinum-A toxin injections.Setting: Neurourology, Swiss Paraplegic Center, Balgrist University Hospital, Zurich, Switzerland.Methods: In all, 28 patients with severe neurogenic detrusor overactivity but preserved bladder sensibility were treated with botulinum-A toxin injections into the detrusor muscle. A measure of 300 u of botulinum-A toxin (Botox®) was injected at 30 sites sparing the trigone. Prior to the injection, the bladder was anesthesized with conventional lidocaine instillation in a group of 10 patients and with lidocaine instillation enhanced by EMDA in 28 patients. The patients scored the injection pain on a 10-point rating scale. Pain rating scores with versus without EMDA enhancement of the lidocaine instillation were analyzed and the costs of the EMDA procedure were compared to general/spinal anesthesia.Results: The mean pain score of the 10 patients who underwent the injections of Botox® after conventional lidocaine instillation was 4.0 (SD 1.6). Following EMDA enhanced lidocaine instillation slight even or no pain occurred during the injections of Botox®, and the mean pain score was 0.5 (SD 0.2). Compared to spinal or general anesthesia, the local anesthesia saved around 15% of the costs.Conclusions: EMDA enhanced instillation of lidocaine enables a sufficient anesthesia of the bladder wall that ensures a painless application of the botulinum-A toxin injections into the detrusor muscle. This method may avoid general or spinal anesthesia in patients with preserved bladder sensibility. It ensures considerable cost reduction, avoids anesthesia-related risks and complications and enables the procedure on an outpatient basis.

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.

Apomorphine sublingual as primary or secondary treatment for erectile dysfunction in patients with spinal cord injury

To evaluate the effectiveness of apomorphine sublingual (SL) 3 mg, as a primary or secondary treatment for erectile dysfunction (ED) in patients with spinal cord injury (SCI), and to determine possible differences in efficacy considering clinical, urodynamic and neurophysiological findings.