Repeat Botulinum Research Articles

Outcomes of bladder neck botulinum toxin injection for female primary bladder neck obstruction-does subjective improvement correlate with an objective assessment?

Common options for management of primary bladder neck obstruction (PBNO) in women include medications and surgical treatment. Less invasive treatment such as bladder neck botulinum toxin injection can be an alternate therapy in patients with failed conservative management. In this study, we describe the subjective and objective outcomes, patient satisfaction, and willingness for repeat treatment with bladder neck botulinum toxin injection in females with PBNO. A retrospective analysis of ten female PBNO patients managed with bladder neck botulinum toxin injection was performed. Subjective parameters were quantified with symptom assessment, International Prostate Symptom Score (IPSS), and Quality of life (QoL) score. Objective parameters were assessed with maximum flow rate (Qmax) in uroflowmetry and postvoid residual (PVR). The mean pre-treatment IPSS, QoL score, Qmax, PVR was 24.2 ± 5.0, 4.8 ± 0.63, 5.73 ± 3.18ml/s, and 210 ± 66ml, respectively. Seven of the ten patients subjectively improved (IPSS 12.9 ± 9.6, QoL2.9 ± 1.6, p < 0.05). Three patients improved objectively (mean Qmax 17.3 ± 2.7ml/s, PVR 42.7 ± 7.5ml, p < 0.05). Three patients accepted repeat botulinum toxin injection. Three patients who showed no improvement underwent bladder neck incision with resolution of symptoms. Botulinum toxin can be an intermediary therapy in female patients with PBNO who want a minimally invasive procedure.

GMFCS level improvement in children with cerebral palsy treated with repeat botulinum toxin injections and intensive rehabilitation: A retrospective study.

The Gross Motor Functional Classification System (GMFCS) provides a standardized classification of motor disability in children with cerebral palsy (CP) that is typically considered longitudinally stable. Here, changes in GMFCS levels of children with CP who received repeated botulinum toxin A (BoNT-A) injections within an intensive rehabilitation approach were evaluated. This retrospective, observational study included 503 children with CP (GMFCS I-V) treated in a single university rehabilitation clinic. Individualized treatment plans and a variety of rehabilitation techniques were incorporated within an integrated model of care. Each child received≥2 repeated BoNT-A injections as well as an intensive rehabilitation program. GMFCS level following repeat treatment improved in 42.1% of the patients and worsened in 3 patients; 14.9% of children showed improvement after 1 treatment cycle, 12.3% after 2 cycles, 7.6% after 3 cycles, 3.6% after 4 cycles, and 3.8% after≥5 cycles. Type of involvement (p < 0.001), baseline GMFCS (p = 0.001), number of treatment cycles (p < 0.001) and presence of severe dystonia (p = 0.032) were significant predictors of GMFCS improvement, but age and gender were not. Children with CP may change GMFCS level when intensive rehabilitation programs are combined with repeated BoNT-A injections.

Impact of integrated upper limb spasticity management including repeat botulinum toxin type A (BoNT-A) injections on patient-centred goal attainment in real-life practice: results from the prospective, observational Upper Limb International Spasticity cohort study (ULIS-III) in a Russian subpopulation

To assess the longitudinal attainment of patient-centred and function related goals after integrated spasticity management including repeated cycles of botulinum toxin A type A (BoNT-A) injections in real life settings over a period of 2 years. The article presents analysis of the results within the subpopulation of patients from Russia. This international, multicentre, observational, prospective, longitudinal cohort study (registered at clinicaltrials.gov as NCT02454803) included patients ≥18 years old with upper-limb spasticity of any aetiology in whom a decision had already been made to inject any BoNT-A formulation commercially available in the Russi. The treatment outcomes were evaluated using the Upper Limb Spasticity Index, which combines the patient-centred Goal Attainment Scaling (GAS) with a set of targeted standardised measures to assess the neurological impairment. The extent of functional impairment was assessed using the DAS. 168 Russian patients from 7 sites with a mean age of 49.8 years participated in the study. The Russian subpopulation had some differences from the overall study population in baseline characteristics of patients and injection practices of BoNT-A treatment. During the study period, the majority of Russian patients received AboBoNT-A (Dysport) injections - 142 (85%) patients at cycle 1, while OnaBoNT-A (Botox) was used in 14 (8%) patients, and IncoBoNT-A (Xeomin) - in 12 (7%) patients. Higher doses of AboBoNT-A were observed compared to the overall population, mean doses of AboBoNT-A between cycles 1 and 4 were 909-934 U in the Russian patients and 814-859 U in the overall population. In general, patients of the Russian subpopulation successfully achieved their treatment goals. The mean cumulated GAS T-score over the study was 51.1±3.0, marginally exceeding the same parameter in the overall population (49.5±5.9). Across the 6 goal domains, cumulated GAS T-scores in Russian subpopulation were highest for the goals related to passive function and pain relief, with mean scores of 51.8±4.2 and 51.6±4.8, respectively. In the overall population cumulated GAS T-scores were highest for involuntary movements (mean 50.5±5.6) and pain relief (mean 50.4±6.2). The lowest GAS T-scores were for the treatment goals related to active function in both Russian subpopulation and overall population, the mean scores were 48.3±5.5 and 46.6±7.4 respectively. The study results also showed significant improvement in in terms of reduction of muscle tone according to MAS (Modified Ashworth Scale) and the extent of functional impairment according to DAS (Disability Assessment Scale). The results of this subgroup analysis on patients from Russia showed high effectiveness of repeated cycles of BoNT-A injections as part of the integrated upper limb spasticity management conducted in real life settings, both in terms of reduction of muscle tone and correction of functional impairment, which contributes to the successful achievement of the treatment goals. The right choice of individual patient-centred treatment goals and methods for assessing their achievement are important components of the treatment and rehabilitation process for patients with spastic paresis of the upper limb.

Longitudinal goal attainment with integrated upper limb spasticity management including repeat injections of botulinum toxin A: Findings from the prospective, observational Upper Limb International Spasticity (ULIS-III) cohort study.

ObjectiveTo assess the longitudinal effects of integrated spasticity management incorporating repeated cycles of botulinum toxin A type A (BoNT-A) over 2 years.MethodsThe Upper Limb International Spasticity study was a prospective, observational, cohort study following adult patients over 2 years of integrated upper-limb spasticity management including repeat botulinum toxin (BoNT-A) treatment (any commercially-available product).ResultsA total of 1,004 participants from 14 countries were enrolled, of which 953 underwent ≥ 1 BoNT-A injection cycle (median 4 cycles) and had ≥ 1 goal attainment scaling assessment. Most participants (55.9–64.6% across cycles 1–6) saw a therapist after BoNT-A treatment; the most frequent therapy intervention was passive stretch (70.1–79.8% across cycles 1–6). Patients achieved their goals as expected over repeated cycles; mean cumulated goal attainment scaling T-score at 2 years was 49.5 (49.1, 49.9). Mean goal attainment scaling change scores of ≥ 10 were maintained across up to 7 cycles. Higher rates of goal achievement were seen for primary goals related to passive vs active function (86.6% vs 71.4% achievement). Standardized measures of spasticity, pain, involuntary movements, active and passive function improved significantly over the study.CONCLUSIONThis large, international study provides evidence for benefit of repeated cycles of BoNT-A, over 2 years captured through person-centred goal attainment and standardized measures.LAY ABSTRACTThis paper presents the primary efficacy results from the Upper Limb International Spasticity (ULIS-III) study, a large international longitudinal study that explored real-life clinical practice in the integrated management of upper-limb spasticity, using botulinum toxin-A (BoNT-A) in conjunction with physical therapies. The study provides evidence for the sustained functional benefit of repeated cycles of BoNT-A. In particular, those patients who continued to receive repeated injections for up to 7 cycles in 2 years showed relevant goal attainment. Standard outcome measures generally supported the rates of goal achievement; ratings of pain, involuntary movements, active and passive function all improved significantly over each treatment cycle. The successful results from ULIS-III highlight the importance of accurate and clear goal-setting during BoNT-A treatment to help target clinical intervention and the use of focused outcome measurement.

When can maximal efficacy occur with repeat botulinum toxin injection in upper limb spastic paresis?

Repeated injection cycles with abobotulinumtoxinA, a botulinum toxin type A, are recommended in current clinical guidelines as a treatment option for adults with upper limb spastic paresis. However, the magnitude of the maximal therapeutic effect of repeated abobotulinumtoxinA treatment across different efficacy parameters and the number of injection cycles required to reach maximal effect remain to be elucidated. Here, we present a post hoc exploratory analysis of a randomized, double-blind, placebo-controlled trial (12–24 weeks; NCT01313299) and open-label extension study (up to 12 months; NCT0131331), in patients aged 18–80 years with hemiparesis for ≥6 months after stroke/traumatic brain injury. Two inferential methods were used to assess the changes in efficacy parameters after repeat abobotulinumtoxinA treatment cycles: Mixed Model Repeated Measures analysis and Non-Linear Random Coefficients analysis. Using the latter model, the expected maximal effect size (not placebo-controlled) and the number of treatment cycles to reach 90% of this maximal effect were estimated. Treatment responses in terms of passive and perceived parameters (i.e. modified Ashworth scale in primary target muscle group, disability assessment scale for principal target for treatment or limb position, and angle of catch at fast speed) were estimated to reach near-maximal effect in two to three cycles. Near-maximal treatment effect for active parameters (i.e. active range of motion against the resistance of extrinsic finger flexors and active function, assessed by the Modified Frenchay Scale) was estimated to be reached one to two cycles later. In contrast to most parameters, active function showed greater improvements at Week 12 (estimated maximal change from baseline-modified Frenchay Scale overall score: +0.8 (95% confidence interval, 0.6; 1.0) than at Week 4 (+0.6 [95% confidence interval, 0.4; 0.8]). Overall, the analyses suggest that repeated treatment cycles with abobotulinumtoxinA in patients chronically affected with upper limb spastic paresis allow them to relearn how to use the affected arm with now looser antagonists. Future studies should assess active parameters as primary outcome measures over repeated treatment cycles, and assess efficacy at the 12-week time-point of each cycle, as the benefits of abobotulinumtoxinA may be underestimated in the studies of insufficient duration. Abbreviated summary In this post hoc analysis of repeated abobotulinumtoxinA injection cycles in upper limb spastic paresis, Gracies et al. used statistical modelling to elucidate the maximal therapeutic effect of abobotulinumtoxinA. Notably, the number of injections required to reach this maximal effect was higher for active (e.g. active function) compared with passive (e.g. tone) parameters.

The role of intrasphincteric botulinum toxin injection in the management of functional biliary pain: a systematic review and meta-analysis.

The management of postcholecystectomy functional biliary pain or Type III sphincter of Oddi dysfunction is challenging. The Evaluating Predictors and Interventions in Sphincter of Oddi Dysfunction study has demonstrated the lack of efficacy of endoscopic sphincterotomy in the management of Type III sphincter of Oddi dysfunction. Botulinum toxin injection to the sphincter of Oddi has been reported as being effective in uncontrolled studies. We sought to understand its pooled efficacy in controlling pancreaticobiliary pain in a systematic review and meta-analysis. Our literature review yielded 10 studies (416 patients) and on random effects meta-analysis, the pooled efficacy of intrasphincteric botulinum toxin injection in alleviating symptoms of pancreaticobiliary was 49% (complete response) and 64% (partial response). One patient developed mild pancreatitis postprocedure and five patients needed postprocedure hospital admission for pain management. The effect of botulinum toxin injection was transient and in the majority of studies, and a positive response to botulinum toxin injection was followed by an endoscopic sphincterotomy. In one study, relapse of pain was managed by repeat botulinum toxin injections with success. Intermittent botulinum toxin injection could be a potential option in the overall management strategy of patients with Type III sphincter of Oddi dysfunction, in conjunction with medical management with neuromodulatory medication.

Treatment with posterior capsular release, botulinum toxin injection, hamstring tenotomy, and peroneal nerve decompression improves flexion contracture after total knee arthroplasty: minimum 2-year follow-up.

No definite treatment option with reasonable outcome has been presented for old and refractory flexion contracture after total knee arthroplasty (TKA). We describe a surgical technique for 21 refractory cases of knee flexion contracture, including 12 patients with history of failed manipulation under anesthesia (MUA). Retrospective review was conducted for procedures performed by a single surgeon between 2005 and 2016. Twenty-one knees (19 patients) with knee flexion contracture after primary TKA were treated with all the following procedures: posterior capsular release, hamstring tenotomy, prophylactic peroneal nerve decompression, and botulinum toxin type A injections. Twelve of the 21 knees had at least 1 prior unsuccessful MUA before this soft-tissue release procedure. Mean age at intervention was 60years (range 46-78years). Mean preoperative knee range of motion (ROM) was - 27° extension (range - 20° to - 40°) to 100° flexion (range 90°-115°). All radiographs were evaluated for proper component sizing and signs of loosening. Full extension was achieved immediately after surgery in all patients. Only one knee required repeat botulinum toxin type A injection. All patients had full extension at mean follow-up of 31months (range 24-49months). No significant change was observed in knee flexion after the procedure (n.s.). Significant improvement was noted in the postoperative Knee Society Score (KSS) (mean 80, range 70-90) when compared with preoperative KSS (mean 45, range 25-65) (p = 0.008). The proposed surgical technique is efficacious in treating patients with refractory knee flexion contracture following TKA to gain and maintain full extension at minimum 2-year follow-up. IV, retrospective case series.

Is repeat Botulinum Toxin A injection valuable for neurogenic detrusor overactivity-A systematic review and meta-analysis.

To investigate the value of repeat botulinum toxin A (BTX-A) injections in patients with neurogenic detrusor overactivity (NDO). We searched the PubMed, EMBASE, and EBSCO databases for articles published until June 2016. Studies that reported the efficacy and safety of repeat BTX-A injections for adult patients with NDO were eligible. The effect size for each outcome was calculated as the standardized mean difference ± standard error and 95% confidence interval, and was graded as small, >0.2; moderate, >0.5; or large, >0.8. The outcomes included maximum cystometric capacity (MCC), maximum detrusor pressure (MDP), reflex volume (RV), bladder compliance (BC), quality of life (QOL), and injection interval. Descriptive reviews were performed for urinary incontinence (UI) and adverse events (AEs). Eighteen studies involving 1533 patients whose level of evidence ranged from 3 to 4 were included in this study. We noted non-significant changes in MCC, MDP, RV, and BC between the first and last injections. Patients who had received ≤4 injections were found to have stable QOL improvements after the first and last injections, whereas patients who had received ≥5 injections were found to have a significant decrease in QOL after the last injection. No significant differences in injection intervals were noted after repeat BTX-A injections, and the repeat injection failure rate was low. Our study demonstrated that repeat BTX-A injections allow sustained improvements in patients with NDO. The rate of AEs was stable and low. However, additional high-quality, large-scale, and long-term trials are necessary to establish the efficacy and safety of ≥5 repeat BTX-A injections.

Are the medial gastrocnemius muscles of spastic cerebral palsy children altered following repeat botulinum toxin injections when compared with an un-injected muscle?

The purpose of this study was to compare the rotational profile of adults with higher versus lower foot progression angles (FPA). Tibial torsion, femoral torsion, hip internal and external rotation and FPA data were collected on one hundred two healthy volunteers. Data were stratified into Low, Mid, and High FPA groups to study relationships among the components of the rotational profile and if there were group differences in the magnitude of torsion angles. Direction of torsion was also studied as an attempt to look at the incidence of offsetting between the tibia and femur. Tibial torsion was significantly higher in the High FPA group (p < 0.001) and was significantly related to the FPA (p ≤ 0.01). Femoral torsion was related to hip internal rotation (p < 0.05). Offsetting tibial and femoral torsions occurred in 59% of subjects with low FPA and 56% of subjects with high FPA. All subjects in the low FPA group with offsetting had tibial torsion that followed the FPA and the femurs that were directed opposite. In the High FPA group, 68% of subjects with offsetting had tibias that followed the FPA. Stratifying the data by FPA revealed there were significant differences in tibial torsion among the groups and provided evidence that tibial torsion influences the direction and magnitude of the FPA. Offsetting torsions between the tibia and femur were more common in people with higher and lower FPA and had clearer patterns where the tibia tended to follow the direction of the FPA.

Should botulinum toxin A injections be repeated in children with cerebral palsy? A systematic review.

The aim of this study was to determine the effects of repeat botulinum toxin A (BoNT-A) injections in children with spastic cerebral palsy (CP) on the basis of a best evidence synthesis. This study included 13 original articles after searching the literature to retrieve information. We used the critical review form produced by McMaster University to determine the methodological quality of the studies, and then confirmed the levels of evidence from Sackett. The studies were also evaluated using the International Classification of Function, Disability and Health - Children and Youth Version (ICF-CY). A total of 893 children with spastic CP who had been administered repeat BoNT-A injections were evaluated. The evidence level was II in four of the thirteen studies, III in four studies, and IV in five studies. The McMaster review form score was 14 in two studies, 13 in four studies, and 12 in seven studies. The results showed that repeat BoNT-A may be a safe and an effective approach. The first two injections/one repeat especially relieve spasticity and improve fine and gross motor activities. Future studies to investigate the effectiveness of repeat BoNT-A in children with spastic CP may be planned within the framework of the ICF-CY to include well-designed randomized controlled trials and those conducted on larger homogenous groups.

Botulinum toxin therapy for chronic anal fissures: where are we at currently?

Botulinum toxin (Botox) injection for chronic anal fissure (CAF) is commonly performed, yet there remains no consensus on optimal dosage or frequency of injections required to achieve complete resolution of anal fissure. The aim of this study was to determine the effectiveness of Botox and side-effect profile in the management of CAF. A retrospective clinical study of patients between 2010 and 2014 who underwent a Botox injection for CAF at a tertiary centre was performed. The effectiveness of Botox was measured using standardized outcomes including overall healing rate, presence of anal pain, recurrence and need for repeat botulinum injection. Binary outcomes were assessed using logistic regression model. The analysis was performed using Stata version 13 (StataCorp, College Station, TX, USA). One hundred and one patients underwent 126 Botox injections within the study period. The mean first post-operative visit was at 1 month. The overall recurrence rate was 32%. The majority of patients were given 33 U. No statistically significant relationship between dose and recurrence was identified. The presence of pain at the first post-operative visit was a predictor of future recurrence (odds ratio 3.92, confidence interval 1.58-9.74, P = 0.003). Botox is an effective strategy for CAF. Low doses can be given with good efficacy as highlighted by our audit and has the potential for great cost saving. The best predictor of recurrence is the presence of pain at the first post-procedure visit.

Poster 304 Evolution of Injection Technique with Repeat Botulinum Therapy in Patients with Cervical Dystonia

Poster 304 Evolution of Injection Technique with Repeat Botulinum Therapy in Patients with Cervical Dystonia

Poster 179 Evolution of Cervical Dystonia and Patient Satisfaction with Repeat Botulinum Toxin Therapy in Clinical Practice

Poster 179 Evolution of Cervical Dystonia and Patient Satisfaction with Repeat Botulinum Toxin Therapy in Clinical Practice

Repeat botulinum toxin A injections: a step forward in the challenge to evaluate current clinical practice.

This commentary is on the original article by Lidman et al. on pages 754–761 of this issue.

Sciatic perineural edema treated by Botulinum toxin injection on piriformis muscle

An 80-year-old woman presented with right leg and buttock pain since a few months' duration. Paresthesias on the right leg were associated with a prolonged seated position. The right leg visual analog scale score was 6/10. The right side straight leg raise test (Lasègue test) was painless. Magnetic resonance imaging revealed mild bilateral L3–L4 and L4–L5 foraminal stenosis (Fig. 1). Transforaminal steroid injections over right L3–L4 and L4–L5 were performed but the leg and buttock pain did not improve at all. A pelvic magnetic resonance imaging revealed perineural edema of the right sciatic nerve at the level below the right piriformis muscle (Figs. 2 and 3), compatible with piriformis muscle syndrome [ [1] Michel F. Decavel P. Toussirot E. Tatu L. Aleton E. Monnier G. et al. The piriformis muscle syndrome: an exploration of anatomical context, pathophysiological hypotheses and diagnostic criteria. Ann Phys Rehabil Med. 2013; 56: 300-311 Crossref PubMed Scopus (36) Google Scholar ]. Under computed tomography-guidance, 100 IU Botulinum toxin was injected into the right piriformis muscle belly under local anesthesia (Fig. 4, Left and Middle) [ [2] Al-Al-Shaikh M. Michel F. Parratte B. Kastler B. Vidal C. Aubry S. An MRI evaluation of changes in piriformis muscle morphology induced by botulinum toxin injections in the treatment of piriformis syndrome. Diagn Interv Imaging. 2015; 96: 37-43 Crossref PubMed Scopus (33) Google Scholar ]. A repeat Botulinum toxin injection was given 3 months later to boost the muscle atrophy effect. Follow-up pelvic computed tomography demonstrated right piriformis muscle atrophy (Fig. 4, Right). After the second injection, the right leg visual analog scale score improved to 1/10. Fig. 2Sacral T1-weighted coronal magnetic resonance imaging shows right sciatic perineural edema (arrow) when comparing with the left side. View Large Image Figure Viewer Download Hi-res image Fig. 3Serial sacral T1-weighted axial magnetic resonance imaging shows right sciatic perineural edema (arrow) just below the piriformis muscle (asterisk). View Large Image Figure Viewer Download Hi-res image Fig. 4(Left) Before the computed tomography (CT)-guided Botulinum toxin injection, axial imaging shows symmetrical piriformis muscle thickness. (Middle) CT-guided Botulinum toxin was injected over the piriformis muscle belly under local anesthesia. (Right) Follow-up CT imaging revealed right piriformis muscle atrophy (arrow). View Large Image Figure Viewer Download Hi-res image

Selective laryngeal adductor denervation-reinnervation surgery for spasmodic dysphonia

Surgical treatment of adductor-type spasmodic dysphonia provides relief from the disabling voice breaks that require repeat botulinum toxin injections. The selective laryngeal adductor denervation-reinnervation surgery is described here. Key points discussed include patient selection, pertinent laryngeal and neural anatomy, and postoperative course.

Effects of botulinum toxin type a in the bladder wall of children with neurogenic bladder dysfunction: a comparison of histological features before and after injections

Study received institutional review board approval. Supported by the Italian Ministry of Health. * Correspondence: Department of NephroUrology and NeuroUrology Unit, Bambino Gesu Pediatric Hospital, Piazza S Onofrio 4, 00165 Rome, Italy (telephone: 0039.06.68592643; FAX: 0039.06.68592518; e-mail: mosiello@opbg.net). Purpose: Botulinum toxin type A has gained popularity in urology. Most reported studies have been in adults at urology centers and most have addressed long-term safety. Since botulinum toxin type A treatment for neurogenic bladder dysfunction requires repeat injections, verifying that such treatment does not induce fibrosis in children seems essential. Materials and Methods: The study was approved by the institutional review board and patients were enrolled after we obtained written consent. Patients with neurogenic bladder dysfunction not responding to conventional treatment (anticholinergics and clean intermittent catheterization) were treated with 10 IU/kg botulinum toxin type A up to a maximum of 300 IU. Endoscopic cold cup biopsies were obtained from the posterolateral bladder wall 1.5 to 2 cm above the ureteral orifice. Bladder wall findings were categorized into 3 groups, including inflammatory infiltration, edema and fibrosis. Each criterion was then graded as mild or severe and analyzed by Fisher’s exact test (p 0.05). Results: A total of 46 bladder wall biopsies were obtained from 40 patients 2 to 18 years old. Biopsies were evaluated in groups 1 and 2, including group 1—20 from patients with no botulinum toxin type A injection and group 2—20 after botulinum toxin type A injection. Group 2 was subdivided into group 3—10 biopsies after 1 injection and group 4—10 after multiple injections. Six patients underwent biopsy twice, that is before the first and second treatments. Histological changes were present in all biopsies. When comparing groups 1 and 2, there was no statistically significant difference in inflammation and edema. However, there was a significant difference in fibrosis between groups 1 and 4 (p 0.05) with apparently decreased fibrosis after multiple injections. Conclusions: In our experience repeat botulinum toxin type A injections into the detrusor in children do not lead to increased fibrosis in the bladder wall. This study confirms the long-term safety of botulinum toxin type A in the pediatric population.

Effects of Botulinum Toxin Type A in the Bladder Wall of Children With Neurogenic Bladder Dysfunction: A Comparison of Histological Features Before and After Injections

Botulinum toxin type A has gained popularity in urology. Most reported studies have been in adults at urology centers and most have addressed long-term safety. Since botulinum toxin type A treatment for neurogenic bladder dysfunction requires repeat injections, verifying that such treatment does not induce fibrosis in children seems essential. The study was approved by the institutional review board and patients were enrolled after we obtained written consent. Patients with neurogenic bladder dysfunction not responding to conventional treatment (anticholinergics and clean intermittent catheterization) were treated with 10 IU/kg botulinum toxin type A up to a maximum of 300 IU. Endoscopic cold cup biopsies were obtained from the posterolateral bladder wall 1.5 to 2 cm above the ureteral orifice. Bladder wall findings were categorized into 3 groups, including inflammatory infiltration, edema and fibrosis. Each criterion was then graded as mild or severe and analyzed by Fisher's exact test (p <0.05). A total of 46 bladder wall biopsies were obtained from 40 patients 2 to 18 years old. Biopsies were evaluated in groups 1 and 2, including group 1-20 from patients with no botulinum toxin type A injection and group 2-20 after botulinum toxin type A injection. Group 2 was subdivided into group 3-10 biopsies after 1 injection and group 4-10 after multiple injections. Six patients underwent biopsy twice, that is before the first and second treatments. Histological changes were present in all biopsies. When comparing groups 1 and 2, there was no statistically significant difference in inflammation and edema. However, there was a significant difference in fibrosis between groups 1 and 4 (p <0.05) with apparently decreased fibrosis after multiple injections. In our experience repeat botulinum toxin type A injections into the detrusor in children do not lead to increased fibrosis in the bladder wall. This study confirms the long-term safety of botulinum toxin type A in the pediatric population.

Repeat botulinum toxin-A injections for treatment of adult detrusor overactivity

Intravesical injections of botulinum toxin-A have become established as an effective therapy in the management of neurogenic and idiopathic detrusor overactivity that is refractory to treatment with anticholinergic medication. The effects of the toxin are finite and repeated injections are required to sustain the beneficial therapeutic effects. The available data suggest a reproducible and sustained improvement in symptoms as well as urodynamic parameters following repeated injections of botulinum toxin-A. The reported incidence of adverse events is low and resistance to the toxin is uncommon. The timing of repeat injections within the published data is variable, reflecting differing practise among clinicians, but is typically 6-12 months. Larger scale studies are still required to clarify the usefulness of botulinum toxin-A as a long-term treatment in the management of detrusor overactivity.

Botulinum toxin injection in dysphagia syndromes with preserved esophageal peristalsis and incomplete lower esophageal sphincter relaxation

Botulinum toxin injection into the lower esophageal sphincter (LES) treats dysphagia syndromes with preserved peristalsis and incomplete LES relaxation (LESR). We evaluated clinical and esophageal motor characteristics predicting response, and compared duration of efficacy to similarly treated achalasia patients. Thirty-six subjects (59 ± 2.2 years, 19F/17M) with incomplete LESR on high resolution manometry (HRM) treated with botulinum toxin injection were identified. Individual and composite symptom indices were calculated, and HRM characteristics extracted. Symptom resolution for 6 months was a primary outcome measure, and repeat botulinum toxin injection, dysphagia recurrence or employment of alternate therapeutic approaches were secondary outcome measures. Duration of response was compared using Kaplan-Meier survival curves to a historical cohort of similarly treated achalasia subjects. Response lasted a mean of 12.8 ± 2.3 months. Symptom relief for >6 months was seen in 58.3%; short (<6 months) response was associated with younger age, higher chest pain index, and esophageal body spastic features (P ≤ 0.04). On multivariate logistic regression, chest pain, younger age and contraction amplitudes >180 mmHg independently predicted <6 months relief (P < 0.05 for each). On survival analysis, relief with a single injection extended to 1 year in 54.8% and 1.5 years in 49.8%, statistically equivalent to that reported by 42 similarly treated achalasia subjects (59 ± 3.2 years, 24F/18M). Symptom relief was more prolonged compared to achalasia when repeat injections were performed on demand (P = 0.003). Botulinum toxin injections can provide lasting symptom relief in dysphagia syndromes with incomplete LESR. Prominent perceptive symptoms and non-specific spastic features may predict shorter relief.