Six-Year Follow-Up of Botulinum Toxin A Intradetrusorial Injections in Patients with Refractory Neurogenic Detrusor Overactivity: Clinical and Urodynamic Results

Background

Most reports in the literature on botulinum toxin A (BoNTA) therapy for neurogenic detrusor overactivity (NDO) are based on the results of a single injection. Because most patients may require retreatment, the efficacy and safety of multiple injections must be addressed clearly.

Objective

To investigate the effectiveness and safety of BoNTA intradetrusorial injections in a group of spinal cord–injured (SCI) patients with refractory detrusor overactivity (DO).

Design, setting, and participants

Seventeen SCI patients were prospectively included in the study and followed up to 6 yr.

Intervention

All patients received repeat intradetrusorial injections of BoNTA 300 units (Botox, Allergan, Irvine, CA) under cystoscopic control on an inpatient basis.

Measurements

The preliminary assessment included voiding diary, urodynamics, kidney and bladder ultrasound, and cystourethrography. Patients also completed a standardised quality-of-life (QoL) questionnaire. Clinical evaluation, urodynamics, urinary tract imaging, and QoL assessment were repeated every year throughout the follow-up.

Results and limitations

Before treatment, all patients complained of urinary incontinence and had DO. Bilateral and monolateral renal pelvis dilatation were detected in six and five patients, respectively, and a monolateral and third-grade vesicoureteral reflux was observed in three. At 6-yr follow-up, a significant decrease in the frequency of daily incontinence episodes (p < 0.01), a significant increase in first uninhibited detrusor contraction and in maximum bladder capacity (p < 0.001 for both), and a significant decrease in maximum pressure of these contractions (p < 0.01) were observed. Fifteen patients (88.2%) were completely continent. Renal pelvis dilatation and vesicoureteral reflux resolved in all cases, and the QoL index significantly increased. Limitations of the study are related to the small number of included patients.

Conclusions

In SCI patients with refractory NDO who do not want or are unfit for invasive reconstructive surgery, BoNTA intravesical treatment represents a valid alternative to control DO and urinary incontinence and to preserve upper urinary tract function over a long-term follow-up.     

Adverse Events of Intravesical Botulinum Toxin A Injections for Idiopathic Detrusor Overactivity: Risk Factors and Influence on Treatment Outcome

Background

Intravesical injection of botulinum toxin type A (BoNTA) provides effective treatment for detrusor overactivity and overactive bladder (OAB). However, the high rates of treatment-related adverse events (AEs) prevent its more widespread use.

Objective

To investigate the risk factors of increasing AEs after BoNTA injection for idiopathic detrusor overactivity (IDO).

Design, setting, and participants

This study included a total of 217 patients receiving their first intravesical BoNTA injection for refractory IDO in a tertiary university hospital from 2004 to 2009.

Measurements

AE incidence was analyzed according to gender, age, comorbidities, prostate condition in men, OAB subtype, BoNTA dose, injection site, and baseline urodynamic parameters. Successful outcome was determined based on patient perception of improvement of bladder condition at 3 mo.

Results and limitations

Successful outcomes were reported by 144 (66.3%) patients. By multivariable analysis, male gender (p = 0.013) and baseline postvoid residual (PVR) ≥100 ml (p = 0.003) were independent predictors of acute urinary retention (AUR). Baseline PVR ≥100 ml (p = 0.007) and receiving >100 U BoNTA (p = 0.029) were predictors of straining to void. The incidence of large PVR after treatment was associated with comorbidity (p = 0.011). Urinary tract infection occurred more frequently in women (p = 0.003) and in men with retaining prostate (p = 0.008). No AUR developed after bladder base/trigonal injection. Nevertheless, the occurrence of AUR or large PVR did not affect therapeutic outcome. This study is limited by nonconsecutive enrollment of patients.

Conclusions

Male gender, baseline PVR ≥100 ml, comorbidity, and BoNTA dose >100 U are risk factors for increasing incidence of AEs after intravesical BoNTA injection for IDO.     

Efficacy and Tolerability of Botulinum Toxin Type A in Patients with Neurogenic Detrusor Overactivity and Without Concomitant Anticholinergic Therapy: Comparison of Two Doses

Background

Botulinum toxin type A (BoNTA) has been reported to be effective for treatment of patients with neurogenic detrusor overactivity (NDO) refractory to anticholinergic agents. However, in most of the studies, the efficacy was associated with concomitant use of anticholinergics.

Objective

To evaluate the efficacy and tolerability of BoNTA and compare two different doses in patients with NDO without concomitant anticholinergics.

Design, setting, and participants

Between 2004 and 2006, adults with NDO refractory to anticholinergics or discontinued anticholinergics due to adverse events or contraindications from four different French clinical centres were included in a prospective, randomised, double-blind, comparative trial. Inclusion criteria were urinary incontinence (UI) resulting from NDO that could not be managed with anticholinergics. Patients with bladder cancer, lithiasis, or urinary infection were excluded.

Intervention

Patients were randomised to receive an intradetrusor injection of 500 U or 750 U of BoNTA.

Measurements

The initial evaluation (ie, clinical and urodynamic variables and quality of life [QoL]) was repeated at days 30, 90, 180, and 360. Primary outcome was complete continence rate at day 30. Secondary outcomes were cumulative incontinence rate, reappearance of leakages, pad usage, urodynamics, and QoL.

Results and limitations

Seventy-seven patients received 500 U (n = 39) or 750 U (n = 38) of BoNTA and were included in the full analysis set for efficacy analysis. Complete continence at day 30 was observed in 22 patients (56.4%) and 28 patients (73.7%) receiving 500 U or 750 U of BoNTA, respectively (p = 0.056; one-sided χ² test to compare to α = 0.025). The median delay in the reappearance of leakages was 168 d. Monotherapy of BoNTA significantly improved UI in patients with NDO. Although there was a trend towards a greater improvement with 750 U of BoNTA, no statistically significant differences in terms of clinical and urodynamic variables and QoL were found between the treatment groups. Tolerability was excellent and equivalent for both doses.

Conclusions

Monotherapy of BoNTA at Dysport (Ipsen, Brisbane, CA, USA) doses of 500 U or 750 U seems to be effective and well tolerated in patients with NDO.     

Treatment of Hypertrophic Scars With Intralesional Botulinum Toxin Type A Injections: A Preliminary Report

Background  Hypertrophic scar is the abnormal appearance of wound healing that usually causes major physical, psychological, and cosmetic problems. Treatment of the hypertrophic scar still is a dilemma due to the lack of effective and excellent methods and agents. Recent reports show that botulinum toxin type A (BTX-A) improves wound healing. Therefore, the authors hypothesized that BTX-A may be favorable for the improvement of hypertrophic scars. Methods  A total of 19 patients were randomly assigned to a prospective clinical study. At 1-month intervals, BTX-A (2.5 U per cubic centimeter of lesion) was injected in these patients for a total of 3 months. All the patients were followed up for at least half a year. Therapeutic satisfaction was recorded, and the lesions were assessed for erythema, itching sensation, and pliability. Results  The study was completed by 19 patients. At the half-year follow-up visits, all the patients showed acceptable improvement, and the rate of therapeutic satisfaction was very high. The erythema score, itching sensation score, and pliability score after the BTX-A injection all were significantly lower than before the BTX-A injection. The differences all were statistically significant (P < 0.01). Conclusion  For the treatment of hypertrophic scars, doctors and patients both found BTX-A acceptable because of its better therapeutic results. Its effect of eliminating or decreasing hypertrophic scars was promising. Zhibo Xiao and Fengmin Zhang are the primary authors of this article.     

In the Human Urothelium and Suburothelium,Intradetrusor Botulinum Neurotoxin Type A Does Not Induce Apoptosis: Preliminary Results

Background

Intradetrusor injections of botulinum neurotoxin type A (BoNTA) are emerging as the preferred second-line treatment for neurogenic and idiopathic overactive bladder (OAB). In animal experiments, intradetrusor BoNTA injections have been shown to cause apoptosis in the bladder urothelium and suburothelium but not the detrusor.

Objective

To investigate BoNTA-induced apoptosis in patients with refractory neurogenic OAB.

Design, setting, and participants

Twelve refractory OAB patients with neurogenic detrusor overactivity resulting from multiple sclerosis (MS) and seven controls were included prospectively.

Measurements

The number of apoptotic cells before and 4 wk after first intradetrusor BoNTA (300 U of BOTOX [Allergan, Irvine, CA, USA]) injections were estimated using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) staining.

Results and limitations

Comparison of TUNEL-positive cells (yes vs no) in the bladder urothelium and suburothelium revealed no significant differences in OAB patients before (4 of 12, 33%) versus after (3 of 12, 25%) BoNTA treatment (p = 0.99). In addition, no significant differences (p = 0.99) were found in OAB patients versus controls. Because our findings are based on first intradetrusor BoNTA injections only, it is unclear whether the results could be extrapolated to repeat injections.

Conclusions

In contrast to preliminary animal experiments, first intradetrusor BoNTA injections for treating refractory neurogenic OAB—a highly effective treatment—did not induce apoptosis in the bladder urothelium and suburothelium.     

Repeated botulinum toxin type A injections for refractory overactive bladder: medium-term outcomes, safety profile, and discontinuation rates

Background

Efficacy and safety of botulinum toxin type A (BoNTA) injection is supported by level 1 evidence, but data regarding repeated injections are limited in patients with refractory overactive bladder (OAB) and idiopathic detrusor overactivity (IDO).

Objectives

Describe medium-term outcomes and discontinuation rates for patients adopting repeated BoNTA as a management strategy for IDO.

Design, setting, and participants

Prospective data from a single centre were collected from the first 100 patients.

Intervention

Bladder injection of BoNTA (predominantly 200 U onabotulinumtoxinA; Allergan Ltd., Marlow, Buckinghamshire, UK) in an outpatient setting.

Measurements

OAB symptoms, quality of life, discontinuation rates, interinjection interval, and adverse events were recorded. Data comparisons were performed using a generalised linear model or a chi-square test where appropriate.

Results and limitations

Two hundred seven injections were performed in 100 patients. All patients had 1 injection, 53 had a total of 2, 20 had 3, 13 had 4, 10 had 5, 5 had 6, 3 had 7, 1 had 8, 1 had 9, and 1 had 10 injections. Statistics were applied up to five repeated injections. A statistically significant reduction in frequency, urgency, and urge urinary incontinence were seen following the first BoNTA injection compared to baseline. This improvement was maintained after repeated injections and was not statistically different when comparing differences between injections. Thirty-seven patients stopped treatment after the first two injections; thereafter, dropouts were rare. The most common reasons for discontinuing treatment were poor efficacy (13%) and clean intermittent self-catheterisation (CISC)–related issues (11%). The incidence of CISC after the first injection was 35%. Bacteriuria was detected in 21% of patients. The mean interinjection interval was 322 d. Limitations included the concurrent use of antimuscarinic drugs in some patients.

Conclusions

BoNTA can provide a safe and effective medium-term management option for patients with refractory IDO. The most common reasons cited for stopping treatment were poor efficacy and CISC-related issues.     

The Incontinence Outcome Questionnaire: an instrument for assessing patient-reported outcomes after surgery for stress urinary incontinence

The aim of this study is to develop and psychometrically test a questionnaire (Incontinence Outcome Questionnaire, IOQ) for assessing quality of life (QOL) after surgery for stress urinary incontinence that can be used as a single measurement after the intervention. A total of 171 patients who underwent the tension-free vaginal tape (TVT/TVT-O) operation for stress urinary incontinence completed the King′s Health Questionnaire (KHQ), the Short Form-12 (SF-12) and the IOQ. The internal consistency, internal and external validity and responsiveness of the IOQ were tested. The IOQ–QOL subscale showed good internal consistency (Cronbach’s alpha = 0.83) and significant correlations with the KHQ and the SF-12 scales (r = 0.30–0.56). Partial correlations with objective parameters showed a significant relation for the IOQ–QOL subscale with objective continence/incontinence. The results of our study suggest that the IOQ is a valid and reliable instrument for assessing QOL after incontinence surgery and can be used if baseline or pre-operative data are unavailable.     

Botulinum toxin type A for the treatment of chronic neck pain after neck dissection

BACKGROUND: Neck dissection surgery is often followed by chronic head and neck pain. To date optimal treatment of this type of pain is lacking. Botulinum toxin type A (BTX-A) has been shown to be effective in the treatment of myofascial pain syndrome and headache. In a pilot study, we wanted to test the effectiveness of BTX-A for the treatment of chronic neck pain after neck dissection. METHODS: Sixteen patients with chronic neck pain after neck dissection were included in this prospective, open study. Eighty to 320 units of BTX-A (Dysport) were injected into muscular trigger points. Outcome measures included chronic pain and shooting pain on the basis of visual analog scales and quality of life improvement (EORTC QLQ-C-30; EORTC QLQ-H and N35) before and 4 weeks after treatment. RESULTS: Patients showed a significant reduction in chronic pain (4.5 before to 3.3 after treatment, p =,005) and in shooting pain (6.1 before to 4.7 after treatment, p =.005). There was a trend toward improvement in global quality of life (QLQ-C30, p =.097) and an increase on the functional scale "pain" (QLQ-H and N35, p =.071). CONCLUSIONS: BTX-A treatment of subjects with chronic neck pain after neck dissection resulted in a fast and significant reduction of pain. A significant improvement in quality of life may be expected in a longer time course after treatment.     

Botulinum Toxin Injection in Long-Standing Facial Paralysis Patients: Improvement of Facial Symmetry Observed up to 6 Months

Background  Despite modern reanimation surgical techniques, facial paralysis presents with functional and aesthetic deficits. We evaluated facial symmetry after treating with botulinum toxin the healthy side of the face of 25 patients with long-standing facial paralysis who had previously been treated by surgical methods, with 6 months follow-up. Methods  Evaluation consisted of a clinical score, the two subscales of the Facial Disability Index, and surface electromyography. The mean botulinum toxin dose was 38 ± 5 U (range = 15–69 U). Results  The clinical score showed significant reduction of asymmetry of 48.4% at 1 month and 16.8% after 6 months. The initial result was a consequence of reduced motion on the treated side combined with better motion on the paralyzed side. At 6 months, the treated side returned to basal scores. The residual effect seen in symmetry was due to an increase (18%) of motion in the paralyzed side. There was a significant decrease in the action potential of muscles on the nonparalyzed side 1 month post injection but completely reverted after 6 months. The Physical Function Index increased, but not significantly. The Social/Well-Being Function Index showed a significant increase at 6 months compared to pretreatment. Conclusion  The proposed treatment improved facial symmetry for up to 6 months. Even after the end of the clinical effect of the drug, the paralyzed side’s clinical score was 18% higher than pretreatment, with an increased quality of life.     

Improvement in quality of life after botulinum toxin‐A injections for idiopathic detrusor overactivity: results from a randomized double‐blind placebo‐controlled trial

OBJECTIVE

To determine whether botulinum toxin‐A (BTX‐A) treatment has an effect on the quality of life (QoL) of patients with overactive bladder (OAB) refractory to anticholinergics.

PATIENTS AND METHODS

This was a single centre, randomized, double‐blind, placebo‐controlled trial. Participants were men and women with idiopathic detrusor overactivity (IDO). Participants were randomised to receive either 200 U of BTX‐A (Botox®, Allergan Inc., Irvine, CA, USA; n = 16) or placebo (n = 18) via a trigone‐sparing flexible cystoscopic technique. QoL was assessed using the King’s Health Questionnaire (KHQ) at baseline and at 4 and 12 weeks, after injection. At 12 weeks patients were ‘unblinded’ and a further open‐label follow‐up in the BTX‐A group occurred at 24 weeks. The changes in the subdomains of the KHQ were assessed over the study period.

RESULTS

Overall QoL was significantly improved in the BTX‐A treated patients compared with placebo in the blinded part of the study. When analysing the KHQ subdomains, ‘Incontinence Impact’, ‘Emotions’, ‘Physical Limitations’, ‘Social Limitations’ and ‘Severity Measures’ were significantly improved in those that received BTX‐A compared with placebo. The ‘Symptom Severity’ domain was also significantly improved at 4 weeks but not at 12 weeks. At 12 weeks ‘Role Limitations’ also became statistically significant in favour of BTX‐A. The open‐label extension study suggested these benefits last for at least 24 weeks.

CONCLUSIONS

BTX‐A bladder injections at 200 U appear to improve QoL in patients with OAB symptoms and IDO refractory to anticholinergics for at least 24 weeks. As well as the improvement seen in clinical parameters with this form of therapy, perhaps of more importance to the patient, is the improvement in QoL.     

Botulinum toxin type a is a safe and effective treatment for neurogenic urinary incontinence: results of a single treatment, randomized, placebo controlled 6-month study

PURPOSE: We determined the safety and efficacy of each of 2 doses of botulinum toxin type A (BTX-A) (200 or 300 U BOTOX) injected into the detrusor for urinary incontinence caused by neurogenic detrusor overactivity of predominantly spinal cord origin. MATERIALS AND METHODS: A total of 59 patients with urinary incontinence caused by neurogenic detrusor overactivity (due to spinal cord injury in 53 and multiple sclerosis in 6) requiring clean intermittent self-catheterization were randomized to receive a single dose into the detrusor of BTX-A (200 U or 300 U) or placebo. Changes in daily frequency of urinary incontinence episodes were monitored via a patient bladder diary during 24 weeks. Key urodynamic assessments (maximum cystometric capacity, reflex detrusor volume and maximum detrusor pressure during bladder contraction) were used to provide objective measures of the treatment effect on bladder function. The impact of treatment on quality of life was assessed using the Incontinence Quality of Life questionnaire. RESULTS: There were significant posttreatment decreases in incontinence episodes from baseline in the 2 BTX-A groups (p 相似文献