Botulinum toxin in urinary incontinence

PURPOSE OF REVIEW: In recent years, botulinum toxin has been investigated for treatment of lower urinary tract dysfunction. This review discusses recently published literature related to the role of botulinum toxin in treating incontinence, including the place for repeated treatment, the differing types of toxin available and the side effects of its use. RECENT FINDINGS: Botulinum toxin is safe and effective in improving both urodynamic and subjective parameters. The A serotype has a longer duration of action than the B serotype and has fewer systemic side effects; hence, it is more likely to gain favour as a suitable treatment, both in patients with neurogenic detrusor overactivity and those with idiopathic detrusor overactivity. It is especially effective in reducing incontinence associated with detrusor overactivity, and repeated treatments appear safe and efficacious. A better understanding of urothelial physiology suggests that botulinum toxin not only has efferent effects but also acts on afferent pathways. The existing data as they stand at present would also suggest it to be safe in patients of all age groups. SUMMARY: Botulinum toxin is awaiting approval for use in lower urinary tract dysfunction. Studies have been carried out in varying populations, but few have used reduction in incontinence episodes as a primary end point. The short-term and long-term efficacy and safety of botulinum toxin as a treatment modality for those with lower urinary tract dysfunction, especially for those with detrusor overactivity refractory to anticholinergics, is, however, evidenced increasingly. Further investigation is needed, specifically large randomized placebo-controlled trials, to determine the ideal conditions for the use of botulinum toxin. Some such trials are underway and we look forward to their findings with interest.     

Botulinum A toxin as a treatment for overactive rectum with associated faecal incontinence

Aim Rectal hypercontractility can lead to faecal incontinence (FI). Botulinum toxin (BT) has been used successfully for the treatment of bladder overactivity. This study aimed to evaluate the therapeutic value of intrarectal injections of BT in inhibiting colorectal contractions and relieving FI in patients suffering from FI as a result of overactive rectal contractions. Method A prospective open study was carried out in Rouen University Hospital. Six patients (four men and two women) with severe FI related to overactive rectal contractions underwent intrarectal submucosal injections of BT placed in three rows of 10, 1‐ml injections (50 U/1 ml; Dysport^®) starting 1 cm above the dentate line and repeated twice, at intervals of 5 cm proximally. The end‐points included improvement in the FI score, in faecal incontinence quality of life (FIQL) and of manometric abnormality. Results All patients reported improvement in the FI score [18.2 ± 1.1 at baseline vs 9.0 ± 1.7 at 3 months (P = 0.04)] and in FIQL. Rectal contractile activity was reduced. The frequency of contractions remained unaffected (28.1 ± 6.6/h; P = 0.46 vs baseline). High‐amplitude contractions of > 50 cmH₂O were significantly decreased in all patients (16.6 ± 3.9 vs 6.6 ± 4.1/h; P = 0.03). Conclusion Patients with an ‘overactive rectum’ are a heterogeneous group, with varying causes of dysfunction. The dose of BT used was arbitrarily selected. Nevertheless, the study introduces a further therapeutic option in the treatment of FI caused by rectal overactivity.     

Botulinum toxin injections in the management of non-neurogenic overactive bladders in children

Introduction

Non-neurogenic detrusor overactivity in children leads to varying degrees of functional impairments (urinary urgency, pollakiuria, urge incontinence, nocturia). Botulinum toxin has shown its effectiveness in the management of detrusor overactivity in neurological patients.

Objectives

To evaluate the relevance of intravesical Botulinum toxin injections for the treatment of non-neurogenic overactive bladders in children. These pediatric patients were resistant to all the usual therapeutics (e.g. bladder/bowel rehabilitation, anticholinergic drugs, management of diet/hygiene habits and constipation, percutaneous posterior tibial nerve stimulation).

Materials and methods

8 children (mean age: 12.5 years), 5 girls, 3 boys with daytime and/or nighttime incontinence and non-neurogenic detrusor overactivity validated by urodynamic testing. Urodynamic testing was conducted before the injections as well as 6 weeks and 1 year post injections. We used Dysport® 8 Speywood Units/kg injected via cystoscopy into 25 different sites.

Results

We noted improvements without any complaints during bladder voiding for all patients, in 6 patients the overactivity disappeared after 1 injection. Compliance was improved early-on in half the cases and at 1 year for all cases (from 12% to 61%, p = 0.01). Noninhibited contractions decreased constantly in both frequency and intensity. Clinical symptoms improved: mean of 7.75 daytime urinary incontinence episodes (IE) per week before the injection vs. 3 after the procedure (p = 0.04). For nighttime IE the improvement was even more noticeable with 7.38 nighttime IE episodes per week before the injection vs. 2.06 after the procedure (p = 0,02).

Conclusion

Intradetrusor Botulinum toxin injections are a potential therapeutic option for the management of non-neurogenic detrusor overactivity in children resistant to the usual treatments.     

Botulinum toxin injections for neurogenic and idiopathic detrusor overactivity: A critical analysis of results

OBJECTIVE: In recent years there has been an increasing use of the botulinum neurotoxins for the management of conditions characterised by detrusor overactivity. Early studies showed promising results in an area where few options previously existed between pharmacotherapy and surgery. This has led to an urgent need to assess the wide range of techniques and therapies available, as well as the efficacy and tolerability of the treatment. We performed a critical analysis of the numerous clinical studies for this novel treatment option in the management of neurogenic and idiopathic detrusor overactivity, with a view to directing further research and assisting urologists in the management of these conditions. METHODS: A systematic review of the literature, as well as a search for abstracts presented to relevant peer-reviewed meetings, was performed. All articles from 1988 onwards were included, prior to which no articles describing urologic use of botulinum neurotoxins had been published, although the majority of the articles have been published since 2000. RESULTS AND CONCLUSIONS: Although many of the studies were small, overwhelming evidence supports the efficacy, safety, and tolerability of the botulinum toxins, specifically serotype A, for the management of these conditions. Before this is accepted as a widespread treatment modality, good-quality evidence from large-scale randomised controlled trials is needed. These studies should identify not only the most appropriate patients to treat but also the best dose, administration technique, and frequency for treatment.     

Botulinum toxin treatment for bladder dysfunction

Botulinum toxin A is available under three different protein complexes that are not interchangeable until appropriate comparative studies are undertaken. The best studied for the treatment of urinary incontinence as a result of neurogenic detrusor overactivity and overactive bladder/idiopathic detrusor overactivity is onabotulinum toxin A. This brand is only approved for the treatment of urinary incontinence as a result of neurogenic detrusor overactivity at a dose of 200 U and idiopathic detrusor overactivity at a dose of 100 U. In patients with detrusor overactivity as a result of spinal cord injury or multiple sclerosis, 200 U of onabotulinum toxin A should be injected in 30 different sites above the trigone. It was shown to be highly effective in curing or decreasing urinary symptoms of incontinence, increasing quality of life, increasing bladder capacity and decreasing maximal detrusor pressure. This effect was independent of the concomitant use of oral anticholinergic drugs. Adverse events were mild, mainly urinary tract infections and high postvoid residual requiring clean intermittent catheterization. In patients with overactive bladder/idiopathic detrusor overactivity, 100 U of onabotulinum toxin A should be injected in 20 sites above the trigone. It markedly decreases urinary incontinence and improves quality of life. Frequency and urgency episodes are also decreased. Adverse events are mild, mainly urinary tract infections and urinary retention. The latter occurred in just 5% of the patients. Candidates for onabotulinum toxin A treatment should be warned that the effect of the toxin is transient and that repeated injections will be required to maintain the effect in the long term. There is no evidence that repeated injections will have a decreased efficacy.     

Botulinum toxin A improves the quality of life of patients with neurogenic urinary incontinence

OBJECTIVE: To evaluate the impact of botulinum toxin type A (BoNTA) on health-related quality of life in patients with neurogenic urinary incontinence (UI) using the Incontinence Quality of Life questionnaire (I-QOL). METHODS: Randomized, double-blind, multicenter, placebo-controlled study involving eight centers across Belgium, France, and Switzerland. Patients (n = 59) with UI due to neurogenic detrusor overactivity (spinal cord injury, n = 53; multiple sclerosis, n = 6) who were inadequately managed on oral anticholinergics received a single dose of BoNTA (200U or 300U, Botox) or placebo. I-QOL scores at screening and after treatment at weeks 2, 6, 12, 18, and 24 were recorded. RESULTS: Median total and subscale I-QOL scores increased significantly from screening with BoNTA 300U compared with placebo at all time points (p<0.05) and with BoNTA 200U compared with placebo at all time points for total score and the Avoidance Limiting Behavior subscale (p<0.05), and at weeks 2, 6, 12, and 18 (p<0.05), but not 24 for the Psychosocial Impact and Social Embarrassment subscales. Approximately twice as many BoNTA recipients as placebo recipients achieved at least a minimal important difference in total I-QOL score at 2, 6, 12, and 24 wk. CONCLUSIONS: BoNTA significantly improves UI-associated health-related quality of life in patients with neurogenic UI.     

Botulinum toxin A for treatment of neurogenic detrusor overactivity and incontinence in patients with spinal cord lesions

OBJECTIVE: To evaluate the efficacy of intravesical botulinum toxin A (BTA) in the treatment of severe neurogenic detrusor overactivity (NDO) with incontinence in patients with spinal cord lesions (SCLs). MATERIAL AND METHODS: Fifteen SCL patients suffering from NDO and incontinence were included in the study. The volume of urine leakage during episodes of incontinence was quantified, and filling cystometry was performed before and after BTA treatment. During BTA treatment, a total of 300 IU of BTA was injected cystoscopically into the detrusor muscle, excluding the trigone region. Antibiotic prophylaxis was given. RESULTS: Thirteen of 15 patients (87%) reported that they were fully continent after treatment and the volume of leakage in the two incontinent patients was significantly reduced. Anticholinergic medication was stopped in all patients after BTA treatment. Cystometry showed a marked reduction in pressures after treatment in all patients, with the maximum detrusor pressure during filling being significantly reduced (p < 0.0005) and the maximum volume at a detrusor pressure of <40 cmH2O being significantly increased (p < 0.0005) in all patients. The maximum bladder capacity was increased, although not significantly. The period during which the patients remained continent following treatment ranged from 4 to 12 months (median 7 months). With the exception of slight haematuria, which resolved spontaneously, no side-effects were observed, and no cases of autonomic hyperreflexia were seen during treatment. CONCLUSION: BTA proved to be a highly effective treatment modality for NDO and incontinence in SCL patients. Treatment was easy to perform and the duration of effect was acceptable. Furthermore, BTA treatment was associated with virtually no side-effects.     

Botulinum toxin and pregnancy

The overall use of botulinum toxin type A in cosmetic procedures continues to rise, and the incidental exposures of pregnant women to the drug can occur. The author describes 2 patients who received botulinum toxin type A injections during pregnancy. The first patient was a 34-year-old woman who received 54 units of botulinum toxin type A to treat periorbital lines (crow's feet) unaware that she was 6 weeks pregnant. She had a healthy term baby delivered by cesarean section; Apgar scores were 9/10. The second patient was a 37-year-old woman who received 65 units of botulinum toxin type A to treat facial dynamic lines (forehead, glabelar, and periorbital), unaware that she was 5 weeks pregnant. She had a healthy term baby delivered by cesarean section; Apgar scores were 9/10. The 2 patients were injected only once in the first trimester. Both cases did not have any complications or detectable adverse effects on the fetuses.     

Urethral injections for female stress incontinence

Emphasis on minimally invasive options for the surgical treatment of stress urinary incontinence (SUI) has resulted in the development of agents and techniques that improve these conditions substantially towards social continence, but currently give suboptimal cure/dry rates. The application of injectable therapy as an office procedure implies the potential for cost-efficient treatment for selected patients with UI. Continuous advances in materials technology have provided the possibility that many new urethral bulking agents will soon be available. Experience continues to accrue in clinical trials for urethral bulking with these agents, while parallel use for the indication of paediatric vesico-urethral reflux has also provided evidence of biological activity related to these compounds. The agents that are closest to complete analysis are synthetic and represent various material types and characteristics. As these materials develop, understanding of the preferred injection technique also is being gained. The delivery method and site might prove to substantially alter the biological activity of these compounds.     

Botulinum toxin for the lower urinary tract

Botulinum toxins (BoNTs) are known for their ability to potently and selectively modulate neurotransmission for successful long-term treatment of muscle hypercontractility. Recent studies suggest that BoNT has effects on modulation of sensory processing, inflammation and glandular function. Urologists and urogynaecologists have become interested in the potential application of BoNTs in patients with lower urinary tract symptoms, including detrusor and sphincter overactivity, bladder hypersensitivity, interstitial cystitis/painful bladder symptoms and benign prostatic hyperplasia. We review the biological action of BoNT in bladder and prostate, and present the techniques and results of the clinical studies with BoNT in the lower urinary tract.     

Botulinum toxin therapy for neurogenic detrusor overactivity

Detrusor injection of botulinum toxin (BTX) has shown great promise in the treatment of neurogenic detrusor overactivity (NDO) refractory to conservative therapy. Despite a paucity of prospective evidence, there exists a growing consensus that BTX injection therapy is a well-tolerated, low-risk therapy. Injections result in substantial subjective improvement in continence and quality of life. Moreover, assessment of urodynamic parameters demonstrates objective changes: (1) an increase in maximum cystometric capacity; (2) when applicable, a reduction in maximal detrusor voiding pressures; and (3) an increase in bladder compliance in cases where baseline bladder compliance measures were abnormal. While BTX bladder injection offers both objective and subjective measures of incontinence control, treatment duration is limited by the gradual reinnervation of injected tissue over an approximately 6- to 9-month interval. However, repeat injection cycles do appear to achieve similar levels of efficacy. The objective of this review is to provide a focused summary of the current body of literature, investigating the safety and efficacy of bladder BTX injection in patients with NDO.     

Botulinum A toxin intravesical injections in the treatment of painful bladder syndrome: a pilot study

OBJECTIVE: We evaluated the efficacy and tolerability of botulinum A toxin (BTX-A) intravesical injections in patients affected by painful bladder syndrome with increased urinary frequency, refractory to conventional treatment modalities. METHODS: Twelve women and two men were prospectively included in the study. Under short general anaesthesia patients were given injections of 200 U of commercially available BTX-A diluted in 20 ml 0.9% NaCl. Injections were performed submucosally in the trigone and bladder floor under cystoscopic control. Voiding chart, the Visual Analog Scale (VAS) for pain, and urodynamics were performed before treatment and 1 and 3 mo afterward. RESULTS: Overall, 12 patients (85.7%) reported subjective improvement at 1 and 3 mo follow-up. The mean VAS score was significantly reduced at 1 and 3 mo after treatment (p<0.05 for both); at the same time points daytime and nighttime urinary frequency significantly decreased (p<0.01 and p<0.05, respectively), and bladder cystometric capacity significantly increased (p<0.01). Two patients reported incomplete bladder emptying. We did not detect any systemic side effects during or after treatment. CONCLUSIONS: The results of this pilot study indicate that BTX-A intravesical injections are effective in the short-term management of painful bladder syndrome. By modulating afferent C-fiber activity within the bladder walls, BTX-A significantly improves urodynamic parameters and reduces bladder pain and urinary frequency.     

Botulinum toxin: future developments

The proposed mechanisms of action of botulinum neurotoxin-A (BoNT-A) in the bladder provide new insights that might help to understand better the complex machinery of the bladder wall and the importance of the afferent signalling mechanisms. BoNT-A might thus become to be considered a small revolution in the understanding and treatment of bladder overactivity. However, substantially more clinical and basic scientific data are needed before we can truly claim to comprehend how it influences lower urinary tract function, or its role in managing urological problems.     

Botulinum toxin type A injections for the management of muscle tightness following total hip arthroplasty: a case series

Background  

Development of hip adductor, tensor fascia lata, and rectus femoris muscle contractures following total hip arthroplasties are quite common, with some patients failing to improve despite treatment with a variety of non-operative modalities. The purpose of the present study was to describe the use of and patient outcomes of botulinum toxin injections as an adjunctive treatment for muscle tightness following total hip arthroplasty.     

Botulinum toxin therapy in orthopaedics

Botulinum toxin A plays an important role in the conservative management of problems of the musculoskeletal system. The main indications for its use are disorders of muscle tone and spasticity of various origins, which makes botulinum toxin an important focal treatment in many neurological conditions. Nevertheless, every orthopaedic surgeon who is involved in the conservative management of muscular problems should be familiar with the indications as well as the pharmacology of the substance and its proper injection techniques. By a combination of botulinum toxin injections with a variety of other conservative measures, such as orthotics and plaster cast treatment, its effect can be enhanced and prolonged. Due to the reversibility of its action, exact dose adjustment to the individual is possible.