Heinrich Schulte-Baukloh

Recommendations on the Use of Botulinum Toxin in the Treatment of Lower Urinary Tract Disorders and Pelvic Floor Dysfunctions: A European Consensus Report

CONTEXT The increasing body of evidence and number of potential indications for the use of botulinum neurotoxins (BoNTs) in the lower urinary tract (LUT) underlines the pressing need for evidence-based guidelines. OBJECTIVE A European expert panel consensus conference was convened with the main aim of evaluating the evidence and clinical considerations for the use of BoNTs in the treatment of urologic and pelvic-floor disorders and to propose relevant recommendations. EVIDENCE ACQUISITION The quality of evidence from fully published English-language literature in the PubMed and EMBASE databases was assessed using the European Association of Urology (EAU) levels of evidence (LoE). Recommendations were graded and approved by a unanimous consensus of the panel. EVIDENCE SYNTHESIS The use of botulinum neurotoxin type A (BoNTA) is recommended in the treatment of intractable symptoms of neurogenic detrusor overactivity (NDO) or idiopathic detrusor overactivity (IDO) in adults (grade A). Caution is recommended in IDO because the risk of voiding difficulty and duration of effect have not yet been accurately evaluated. Repeated treatment can be recommended in NDO (grade B). The depth and location for bladder injections should be within the detrusor muscle outside the trigone (grade C). Dosage in children should be determined by body weight, with caution regarding total dose if also being used for treatment of spasticity, and minimum age (grade B). Existing evidence is inconclusive for recommendations in neurogenic detrusor-sphincter dyssynergia, bladder pain syndrome, prostate diseases, and pelvic-floor disorders. The use of BoNTA in the LUT with the current dosages and techniques is considered to be safe overall (grade A). CONCLUSIONS The consensus committee recommends larger placebo-controlled and comparative trials to evaluate the efficacy of single and repeat injections, the duration of effect, the optimal dosage and injection technique, the timing for repeat injection, and the short- and long-term safety of the treatment in LUT and pelvic-floor disorders.

Efficacy of botulinum-a toxin in children with detrusor hyperreflexia due to myelomeningocele: preliminary results

OBJECTIVES The established treatment of children with neurogenic bladder consists of the use of anticholinergic drugs, such as oxybutynin and tolterodine, and clean intermittent catheterization four or five times a day. If anticholinergic drugs and clean intermittent catheterization fail, surgery is often necessary. With the intent of avoiding surgery, we investigated the effect of botulinum-A toxin for treating detrusor hyperreflexia in this group of patients. METHODS The subjects were 17 children (average age 10.8 years) who had detrusor hyperreflexia and were using clean intermittent catheterization four or five times a day. Urodynamic studies were followed by injection of 85 to 300 U of botulinum-A toxin into 30 to 40 sites in the detrusor muscle. Urodynamic follow-up was done 2 to 4 weeks after injection. RESULTS The mean reflex volume increased by 112.1%, from 95.00 plus minus 34.54 mL (range 47 to 147) to 201.45 plus minus 68.57 mL (range 77 to 310) (P <0.005). The maximal bladder capacity increased by 56.5%, from 137.53 plus minus 59.96 mL (range 59 to 242) to 215.25 plus minus 96.36 mL (range 60 to 380) (P <0.005). The maximal detrusor pressure decreased by 32.6%, from 58.94 plus minus 32.32 cm H(2)O (range 19 to 149) to 39.75 plus minus 26.12 cm H(2)O (range 7 to 100) (P <0.005). Detrusor compliance increased by 121.6%, from 20.39 plus minus 26.5 mL/cm H(2)O (range 4.5 to 40) to 45.18 plus minus 45.4 mL/cm H(2)O (range 5.3 to 100) (P <0.01). CONCLUSIONS Botulinum-A toxin injection into the hyperreflexive detrusor muscle seems to be very effective and might be a therapeutic alternative to anticholinergic drugs.

Urodynamic results and clinical outcomes with intradetrusor injections of onabotulinumtoxina in a randomized, placebo-controlled dose-finding study in idiopathic overactive bladder†‡

We assessed the effects of onabotulinumtoxinA (BOTOX®) on clinical and urodynamic variables in patients with idiopathic overactive bladder (OAB) and urinary urgency incontinence (UUI) with or without detrusor overactivity (DO), inadequately managed with anticholinergics.

Botulinum neurotoxin type A in urology: Antibodies as a cause of therapy failure

Objectives:  Botulinum toxin type A (BoNT/A) proved very effective in therapy for hyperactive detrusor or sphincter dysfunction of neurogenic and non‐neurogenic origin. However, therapy may fail. In a search for possible reasons, we investigated the presence of BoNT/A antibodies (BoNT/A‐AB) in patients who were treated more than once and correlated the presence of antibodies with clinical findings.

Persistence of the synaptosomal-associated protein-25 cleavage product after intradetrusor botulinum toxin A injections in patients with myelomeningocele showing an inadequate response to treatment.

To monitor the presence and cleavage of synaptosomal‐associated protein of 25 kDa (SNAP‐25) by botulinum toxin type A (botox‐A), in human detrusor muscle, as the effects of botox‐A in the urinary bladder last significantly longer than when applied for disorders of striated muscles.

Alfuzosin in the treatment of high leak-point pressure in children with neurogenic bladder

Objective  To decrease the detrusor leak‐point pressure (LPP) of > 40 cmH2O in children with a neurogenic bladder, using the α1‐adrenergic blocking agent alfuzosin.

Propiverine vs oxybutynin for treating neurogenic detrusor overactivity in children and adolescents : results of a multicentre observational cohort study

To compare, in a retrospective observational cohort study, the efficacy, tolerability, safety and clinical effectiveness of propiverine and oxybutynin in children and adolescents with neurogenic detrusor overactivity (NDO).

Efficacy and safety of onabotulinumtoxinA therapy are sustained over 4 years of treatment in patients with neurogenic detrusor overactivity: Final results of a long‐term extension study

To present final efficacy/safety results from a prospective, long‐term extension trial of onabotulinumtoxinA for urinary incontinence (UI) due to neurogenic detrusor overactivity (NDO); patients received treatment for up to 4 years.

Urodynamic effects of propiverine hydrochloride in children with neurogenic detrusor overactivity: a prospective analysis

The management of stones in children is often controversial; extracorporeal shock wave lithotripsy appears to be very successful, with excellent clearance rates, and probably better than in adults. For this reason, many maintain that percutaneous nephrolithotripsy might not be required in children. Authors from Pakistan retrospectively assessed their use of percutaneous nephrolithotripsy, finding that it too yields satisfactory results.

Improving the global management of the neurogenic bladder patient: part II. Future treatment strategies.

ABSTRACT Background: Patients with neurogenic bladder represent a small fraction of the total overactive bladder population.As a consequence, development of new therapies in this area has largely focused on idiopathic urinary incontinence. The absence of data for patients with neurological disease has far-reaching implications, affecting reimbursement and physicians’ willingness to prescribe therapies, and limiting access of potential valuable treatments to patients whose lives are significantly impaired by inadequately managed bladder symptoms. Scope: The range of new therapies is increasing. Although many reviews of the overall safety, efficacy and mode of action of such treatments are available, there is limited information on how these treatments will best be used in clinical practice. We considered the current benefits and limitations of the various new licensed and unlicensed therapies and what role each would have in the future management of neurogenic urinary incontinence. Conclusions: A wide range of new treatments have been investigated for the management of overactive bladder; few, however, have been evaluated extensively in neurogenic urinary incontinence. Further studies are required to determine the optimal dosing regimes and formulations for individual sub-populations of neurogenic bladder patients and to determine the cost-effectiveness of these interventions. With the current experience available, two treatment algorithms for a subset of patients with neurological disease have also been proposed, which suggest at which stage of management and in which patients individual therapies for neurogenic urinary incontinence could be used.