Botulinum Neurotoxin A Injection Research Articles

Plasma Metabolomic Changes in Children with Cerebral Palsy Exposed to Botulinum Neurotoxin.

The long-term effect of botulinum neurotoxin A (BoNT-A) on children with cerebral palsy (CP) is unclear, and how the dynamic changes of metabolites impact the duration of effect remains unknown. To tackle this, we collected 120 plasma samples from 91 children with spastic CP for analysis, with 30 samples in each time point: prior to injection and 1, 3, and 6 months after injection. A total of 354 metabolites were identified across all the time points, 39 of which exhibited significant changes (with tentative IDs) (p values <0.05, VIP > 1). Principal component analysis and partial least-squares discriminant analysis disclosed a clear separation between different groups (p values <0.05). Network analysis revealed the coordinated changes of functional metabolites. Pathway analysis highlighted the metabolic pathways associated with energy consumption and glycine, serine, and threonine metabolism and cysteine and methionine metabolism. Collectively, our results identified the significant dynamic changes of plasma metabolite after BoNT-A injections on children with CP. Metabolic pathways associated with energy expenditure might provide a new perspective for the effect of BoNT-A in children with CP. Glycine, serine, and threonine metabolism and cysteine and methionine metabolism might be related to the duration of effect of BoNT-A.

Changes in Cortical Activity in Stroke Survivors Undergoing Botulinum Neurotoxin Therapy for Treatment of Focal Spasticity.

Background: Botulinum NeuroToxin-A (BoNT-A) relieves muscle spasticity and increases range of motion necessary for stroke rehabilitation. Determining the effects of BoNT-A therapy on brain neuroplasticity could help physicians customize its use and predict its outcome.Objective: The purpose of this study was to investigate the effects of Botulinum Toxin-A therapy for treatment of focal spasticity on brain activation and functional connectivity.Design: We used functional Magnetic Resonance Imaging (fMRI) to track changes in blood oxygen-level dependent (BOLD) activation and functional connectivity associated with BoNT-A therapy in nine chronic stroke participants, and eight age-matched controls. Scans were acquired before BoNT-A injections (W0) and 6 weeks after the injections (W6). The task fMRI scan consisted of a block design of alternating mass finger flexion and extension. The voxel-level changes in BOLD activation, and pairwise changes in functional connectivity were analyzed for BoNT-A treatment (stroke W0 vs. W6).Results: BoNT-A injection therapy resulted in significant increases in brain activation in the contralesional premotor cortex, cingulate gyrus, thalamus, superior cerebellum, and in the ipsilesional sensory integration area. Lastly, cerebellar connectivity correlated with the Fugl-Meyer assessment of motor impairment before injection, while premotor connectivity correlated with the Fugl-Meyer score after injection.Conclusion: BoNT-A therapy for treatment of focal spasticity resulted in increased brain activation in areas associated with motor control, and cerebellar connectivity correlated with motor impairment before injection. These results suggest that neuroplastic effects might take place in response to improvements in focal spasticity.

Effect of muscle selection for botulinum neurotoxin treatment on spasticity in patients with post-stroke elbow flexor muscle over-activity: an observational prospective study

Purpose/Aim To investigate the effect of muscle selection for botulinum neurotoxin A (BoNT-A) treatment on spasticity in patients with post-stroke elbow flexor muscle over-activity. Materials and Methods Chronic stroke patients with a deforming spastic paresis in the upper limb (elbow flexion with forearm pronation) who were injected BoNT-A into at least one of elbow flexor muscles (brachialis, brachioradialis, and biceps brachii) were included in this prospective observational study. The main outcome measure was spasticity angle by Tardieu Scale recorded at pre-treatment and week 4 after treatment. Results Three muscle selection groups with sufficient sample size for statistical analysis were able to be created; brachialis (n = 14), biceps brachii (n = 21), and brachialis plus brachioradialis (n = 11). Although there was a significant improvement in spasticity angle within all groups over time (p < 0.05), the change in spasticity angle was not different between the groups (p > 0.05 for each pairwise comparison). However, the magnitude of the change in spasticity angle was larger in the groups in which brachialis was preferred. Conclusions In stroke patients with a spontaneous spastic posture of elbow flexion and forearm pronation, targeting brachialis for BoNT-A injection seems more effective in reducing the severity of spasticity. Clinical trial registration no NCT04036981

Effects of ultrasound-assisted botulinum neurotoxin-A injection in patients with bruxism and masseter hypertrophy.

Objectives This study aims to explore effects of ultrasound-assisted injection of the botulinum neurotoxin-A (BoNT-A) on muscle thickness (MT) in patients with masseter hypertrophy. Patients and methods Between December 2018 and December 2019, a total of 20 patients (3 males, 17 females; mean age: 28±6.9 years; range, 18 to 42 years) with bruxism who underwent BoNT-A injections were reviewed retrospectively. The patients were treated using individualized injection dosages and sites. Assessment methods included length between the tragus and the angle of the mouth, maximal bite force, and MT of the masseter muscle. Follow-up data were collected from the hospital electronic database. Results There were 26 masseter muscles with masseter hypertrophy in 20 patients. There was a significant difference in ultrasonographic measurements of the relaxed and contracted masseter muscles between the baseline and two weeks, one month and three months after the treatment (p<0.05). In the ultrasonographic measurement of the relaxed masseter muscle, post-treatment third month values significantly differed from the second week values. The differences in the measurement of the line between the tragus and the angle of the mouth between the baseline and two weeks, one month and three months after the treatment were statistically significant (p<0.05). In the maximal bite force measurements, no significant difference was observed between the baseline and post-intervention measurements (p>0.05). Conclusion The MT decreases after a single dose of BoNT-A injection in patients with masseter muscle hypertrophy and ultrasonography is a convenient imaging modality for BoNT-A injection to the masseter.

Validation of a new hemifacial spasm grading questionnaire (HFS score) assessing clinical and quality of life parameters

Validation of the new hemifacial spasm (HFS) questionnaire “HFS score” that captures both clinical (HFS clinical) and health-related quality of life (HRQOL) parameters (HFS subjective) in one tool and comparison with a global HRQOL questionnaire. Cross sectional, prospective validation study including 143 subjects (62 HFS patients and 81 healthy volunteers) from the University Eye Hospital Bonn. Patients were interviewed with the new HFS score and the SF-12 questionnaire prior to and 3 weeks after Botulinum neurotoxin A (BoNT-A) injection. All HRQOL-related questions (HFS subjective) were answered on a visual analogue scale (VAS) ranging from 0 (no complaints) to 100% (maximum complaints) by the patients themselves. Reproducibility was tested in a study extension with 10 patients by repeat interviews (telephone/personal). The new HFS score questionnaire provided a reliable clinical assessment and demonstrated that BoNT-A therapy significantly reduced frequency and severity of eye and cheek spasms (p < 0.001; Wilcoxon test). Relevant aspects of HRQOL of HFS patients were assessed with high accuracy and sensitivity. Significant improvements were achieved after BoNT-A injection in five out of eight HRQOL parameters (p ≤ 0.02; Wilcoxon test). Cronbach’s alpha of 0.818 demonstrated good internal consistency. Telephone survey provided comparable results to personal interviews. This new sensitive and specific HFS score seems a reliable instrument to monitor BoNT therapy and customize it to the needs of the individual HFS patient—in clinical studies and daily clinical practice.

Posterior drooling in children with cerebral palsy and other neurodevelopmental disorders.

To evaluate the effect of botulinum neurotoxin A (BoNT-A) injections, submandibular gland excision (SMGE), and bilateral submandibular duct ligation (2DL) for the control of posterior drooling in children with neurological impairment. In a retrospective cohort, children with neurological impairment (e.g. cerebral palsy) treated between 2000 and 2016 were identified. Mean age at time of surgery was 9 years (range 1-21y). The primary outcome was posterior drooling severity by a visual analogue scale (VAS; 0-10) at baseline, 8-weeks, and 32-weeks follow-up. The secondary outcome was lower respiratory tract infections during the follow-up period. Ninety-two patients (out of 475; 47 males, 45 females) were identified. They were undergoing three different treatments: BoNT-A (n=63), SMGE (n=16), and 2DL (n=13). A significant reduction in VAS over time was observed in the total group of 92 patients. After SMGE, VAS decreased significantly from 6.82 (SD 3.40) at baseline to 2.29 (SD 1.93) at 8 weeks, and 2.17 (SD 2.58) at 32 weeks (F[2.34]=11.618, p<0.001). There was no significant decrease after both BoNT-A and 2-DL. Posterior drooling is an unfamiliar, potentially life-threatening condition that is treatable with medication, BoNT-A injections, or surgery. Although all treatments reduced signs and symptoms of posterior drooling, there is a greater effect after SMGE compared to BoNT-A and 2-DL. What this paper adds Submandibular gland excision has better results for posterior drooling than botulinum toxin A or submandibular duct ligation.

Protocol for The Toxin Study: Understanding clinical and patient reported response of children and young people with cerebral palsy to intramuscular lower limb Botulinum neurotoxin-A injections, exploring all domains of the ICF. A pragmatic longitudinal observational study using a prospective one-group repeated measures design

IntroductionBotulinum neurotoxin-A (BoNT-A) is an accepted treatment modality for the management of hypertonia in children and young people with cerebral palsy (CYPwCP). Nevertheless, there are concerns about the long-term effects...

Intermittent serial casting for wrist flexion deformity in children with spastic cerebral palsy: a randomized controlled trial.

To assess the efficacy of intermittent serial casting in conjunction with occupational therapy and botulinum neurotoxin A (BoNT-A) in children with cerebral palsy (CP) presenting spastic wrist flexion deformity. This was a controlled, prospective study in which 34 children (19 females, 15 males; mean [SD] 11y [4y 6mo]) were randomly allocated to casting or control groups in a ratio of 2:1. Both groups were subjected to BoNT-A treatment and occupational therapy. The casting group additionally received a series of progressive casts intermittently for three consecutive weekends. Outcome measures consisted of passive range of motion (PROM) as assessed by goniometer, muscle tone by Modified Ashworth scale (MAS), and spasticity by Tardieu Scale. Assessments were done at baseline, week 4, and week 12. Baseline characteristics of casting and control groups were comparable. PROM, MAS, and Tardieu angle of catch (XV3) of the casting and control groups significantly improved after treatment (p<0.001 for all). Nevertheless the mean change from baseline MAS at week 12, mean changes from baseline PROM, Tardieu XV3, and the spasticity grade (Y) at week 4 and week 12 of the casting group showed statistical superiority over those of the control group (p<0.05 for all). Children with CP presenting spastic wrist flexion deformity might gain additional benefits from supplementary intermittent serial casting as well as BoNT-A injections and occupational therapy. Serial casting could be considered as a complementary treatment to BoNT-A and occupational therapy in children with clinically significant PROM limitations.

Not only gustatory sweating and flushing: Signs and symptoms associated to the Frey syndrome and the role of botulinum toxin A therapy.

The classic symptoms of Frey syndrome are gustatory sweating and flushing. Aims of the study were to describe prevalenceand severity of typical and atypical presentations of the disorder and to assess the effects of botulinum neurotoxin A (BoNT-A) therapy in patients with Frey syndrome after parotidectomy. In this prospective, observational study on 18 patients, we assessed symptom severity before therapy, after 15 days, 1, 3 and 6 months' follow-up with the sweating-flushing-itch-paresthesia-pain (SFIPP) Frey scale specifically designed by the authors themselves for this study. Before BoNT-A injection, all patients (100%) complained gustatory sweating, 80% paresthesia, 77% gustatory flushing, 60% pain and 60% gustatory itch. The SFIPP-Frey overall score and the symptom-specific ones decreased significantly at each post-therapy control. The prevalence of "unusual" manifestations is not negligible. BoNT-A improves symptoms severity. The SFIPP-Frey scale may be useful to assess symptoms and to monitor post-therapy outcomes.

Functional outcomes of botulinum neurotoxin-A injection followed by reciprocal electrical stimulation in children with cerebral palsy: A randomized controlled trial.

The integration of therapeutic approaches is increasingly recommended for children with cerebral palsy, to enhance outcomes. Nevertheless, clinicians still opt for separate or combined therapies based on little credible knowledge. This study endeavored to evaluate the effect of botulinum neurotoxin-A (BoNT-A) injection and reciprocal neuromuscular electrical stimulation (rNMES) and their combination on the upper extremity function in children with spastic hemiplegia. Sixty-four children with spastic hemiplegia (aged 6- 10 years) were randomly assigned to four treatment-based groups [group I (BoNT-A), group II (rNMES), group III (combined BoNT-A and rNMES), and group IV (Control)]. All children received a physical rehabilitation program, thrice/week over three months. Unilateral upper-limb function, bimanual hand function, and real-time arm-hand function were assessed using Melbourne Assessment (MA), Assisting Hand Assessment (AHA), and Pediatric Motor Activity Log (PMAL) scales respectively pre-treatment, post-treatment, and at 6 months follow-up. Post-treatment, group III achieved greater improvement in MA, AHA, and PMAL compared to other groups (all P < 0.05), and the difference remained in favor of group III at the follow-up (all P < 0.05). This study suggests that BoNT-A and rNMES combined are more effective than either of them alone to enhance upper-extremity function in children with spastic hemiplegia.

Botulinum Neurotoxin-A Injection in Adult Cervical Dystonia and Spastic Paresis: Results From the INPUT (INjection Practice, Usage and Training) Survey.

Botulinum toxin-A (BoNT-A) is an effective treatment for cervical dystonia (CD) and spastic paresis (SP), but it requires in-depth knowledge of anatomy and injection techniques. The Ixcellence Network® is an educational programme to provide neurology, neuropaediatrics, and physical medicine and rehabilitation (PMR) specialists with access to best clinical practices and innovations regarding SP and CD management with BoNT-A. To assess the benefits of such educational programmes and identify unmet needs, a multidisciplinary scientific committee designed INPUT (INjection Practice, Usage & Training), an international multicentric survey describing training and practices among this trained and experienced population. A self-completed questionnaire was sent online to 553 trainees and 14 trainers from the Ixcellence Network®. Among the 131 respondents, 92% specialized in PMR (48%) or neurology (44%), with a mean experience of 15.5 years in their clinical fields and 10.9 years of BoNT-A injection. Most of them (98%) reported having received training before performing their first BoNT-A injection and attending specific courses on how to perform it without any instrumental guidance (76%), and with ultrasound (73%), electrical stimulation (44%) or electromyography (41%). In terms of practices, 92% of respondents reported using at least one guidance technique while injecting, with ultrasound being the most used technique (48%). Attending specific courses was significantly associated with greater self-confidence and use, e.g. for injection with ultrasound, mean self-confidence, on a scale from 1 (not confident) to 10 (fully confident), was 7.9 for trained respondents (vs 4.0 for untrained respondents, p < 0.001) of whom 70% stated that they used this technique regularly or systematically (vs. 11% of untrained healthcare professionals (HCPs), p < 0.0001). Moreover, 84% of respondents reported having trained colleagues, residents or fellows through theoretical (70%) or practical teaching in individuals (80%) or in small groups (65%). Overall, 86% of respondents reported a notable increase over the past 5 years of the number of patients treated with BoNT-A. INPUT is the first international survey describing training and practices in SP and CD management of physicians who attended a dedicated educational programme. The results highlighted the importance of training for self-confidence, and the use of specific techniques and new approaches.

Can clinical and urodynamic parameters predict the occurrence of neutralizing antibodies in therapy failure of intradetrusor onabotulinumtoxin A injections in patients with spinal cord injury?

BackgroundThe aim of the study was to clarify whether clinical and/or urodynamic parameters could be used to infer the probability of neutralizing antibody (NAb) formation as a possible cause of therapy failure (non-response, NR) in patients with neurogenic detrusor overactivity (NDO) due to acquired spinal cord injury/disease (SCI/D) treated with intradetrusor botulinum neurotoxin A (BoNT-A) injections.MethodsA retrospective chart review was performed of all patients with SCI/D who underwent both intradetrusor onabotulinumtoxin A injections and the determination of neutralizing antibodies against BoNT-A between January 1, 2002, and December 31, 2018. NR was defined as urodynamically confirmed persistent or reappearing NDO.ResultsA total of 2700 BoNT-A injections in 414 patients were ascertained. In 69 patients with primary NR after the first BoNT-A injection (n = 6) or with secondary NR after more than one BoNT-A injection (n = 63), an antibody analysis was performed. Antibody examination showed 36 (52.2%) negative, 5 (7.2%) borderline and 14 (each 20.3%) each of positive and highly positive values. Subgroup analysis indicated a correlation between NAb formation and the duration of BoNT-A therapy (p = 0.015), the mean number of BoNT-A injections (p = 0.011) and the time interval between BoNT-A applications (< 7 months, p = 0.022). Urodynamic data analysis indicate significant differences with cut-off values of MCC (< 225 ml, p = 0.038) and MDP (> 45 cmH2O, p = 0.040). However, in the regression analysis models, the predictive value for the occurrence of NAb was too low (MCC: ROC AUC 0.62, MDP: ROC AUC 0.52) to distinguish with sufficient certainty between NAb-positive and NAb-negative NR patients.ConclusionsDespite significant correlations, clinical and urodynamic parameters are only partially suitable for predicting antibody formation against BoNT-A.

Repeated intrastriatal application of botulinum neurotoxin-A did not influence choline acetyltransferase-immunoreactive interneurons in hemiparkinsonian rat brain – A histological, stereological and correlational analysis

In Parkinson’s disease, dopamine depletion leads to hyperactivity of cholinergic interneurons in the caudate-putamen (CPu). Botulinum neurotoxin-A (BoNT-A) inhibits the release of acetylcholine in the peripheral nervous system and is also thought to act as a local anticholinergic drug when injected intrastriatally. In hemiparkinsonian (hemi-PD) rats, a unilateral intrastriatal injection of 1 ng BoNT-A significantly diminished apomorphine-induced rotation behavior for at least 3 months, the effect fading thereafter. A second intrastriatal BoNT-A application, 6 months after the first one, led to a stronger and longer-lasting, beneficial behavioral reaction.As a single BoNT-A injection was not cytotoxic in the rat striatum and resembled BoNT-A treatment in clinical practice, here, we investigated the structural outcome of repeated intrastriatal BoNT-A injections with respect to striatal volume, the number of choline acetyltransferase-immunoreactive (ChAT-ir) interneurons and of the length of their dendritic arbors, and the numeric density of ChAT-ir BoNT-A-induced varicosities (BiVs). Repeated unilateral intrastriatal BoNT-A application decreased the volume of the injected CPu, but did not significantly change the number of striatal ChAT-ir interneurons. Also, the total dendrite length of ChAT-ir interneurons after repeated BoNT-A application resembled the values in double vehicle-injected hemi-PD rats. In repeatedly BoNT-A-injected hemi-PD rats, the numeric density of ChAT-ir BiVs in the CPu was increased compared with rats only intrastriatally injected once with BoNT-A. Even repeated BoNT-A injections in rat striata did not cause substantial morphological changes in ChAT-ir neuron, except for the increased numeric density of ChAT-ir BiVs.

Joint and Muscle Assessments of the Separate Effects of Botulinum NeuroToxin-A and Lower-Leg Casting in Children With Cerebral Palsy.

Botulinum NeuroToxin-A (BoNT-A) injections to the medial gastrocnemius (MG) and lower-leg casts are commonly combined to treat ankle equinus in children with spastic cerebral palsy (CP). However, the decomposed treatment effects on muscle or tendon structure, stretch reflexes, and joint are unknown. In this study, BoNT-A injections to the MG and casting of the lower legs were applied separately to gain insight into the working mechanisms of the isolated treatments on joint, muscle, and tendon levels. Thirty-one children with spastic CP (GMFCS I-III, age 7.4 ± 2.6 years) received either two weeks of lower-leg casts or MG BoNT-A injections. During full range of motion slow and fast passive ankle rotations, joint resistance and MG stretch reflexes were measured. MG muscle and tendon lengths were assessed at resting and at maximum dorsiflexion ankle angles using 3D-freehand ultrasound. Treatment effects were compared using non-parametric statistics. Associations between the effects on joint and muscle or tendon levels were performed using Spearman correlation coefficients (p < 0.05). Increased joint resistance, measured during slow ankle rotations, was not significantly reduced after either treatment. Additional joint resistance assessed during fast rotations only reduced in the BoNT-A group (−37.6%, p = 0.013, effect size = 0.47), accompanied by a reduction in MG stretch reflexes (−70.7%, p = 0.003, effect size = 0.56). BoNT-A increased the muscle length measured at the resting ankle angle (6.9%, p = 0.013, effect size = 0.53). Joint angles shifted toward greater dorsiflexion after casting (32.4%, p = 0.004, effect size = 0.56), accompanied by increases in tendon length (5.7%, p = 0.039, effect size = 0.57; r = 0.40). No associations between the changes in muscle or tendon lengths and the changes in the stretch reflexes were found. We conclude that intramuscular BoNT-A injections reduced stretch reflexes in the MG accompanied by an increase in resting muscle belly length, whereas casting resulted in increased dorsiflexion without any changes to the muscle length. This supports the need for further investigation on the effect of the combined treatments and the development of treatments that more effectively lengthen the muscle.

Submandibular duct ligation after botulinum neurotoxin A treatment of drooling in children with cerebral palsy

AimTo assess: (1) the effect on drooling of bilateral submandibular duct ligation as surgical therapy after the administration of submandibular botulinum neurotoxin A (BoNT‐A) for excessive drooling and (2) the predictive value of treatment success with BoNT‐A on treatment success after bilateral submandibular duct ligation.MethodThis was a within‐participant retrospective observational study in which 29 children with severe drooling (15 males, 14 females) received BoNT‐A treatment at a mean age of 9 years 6 months (SD 2y 5mo), followed by bilateral submandibular duct ligation at a mean age of 10 years 11 months (SD 2y 4mo). Fifteen children were diagnosed with cerebral palsy (CP), with 12 children classified in Gross Motor Function Classification System levels IV and V. The 14 children without CP had non‐progressive developmental disorders. The primary drooling severity outcomes were the Visual Analogue Scale (VAS; subjective assessment) and drooling quotient (objective assessment). Measurements were taken before each intervention and again at 8 and 32 weeks.ResultsThe VAS was significantly lower after bilateral submandibular duct ligation at follow‐up compared to BoNT‐A treatment (mean difference −33, p≤0.001; 95% confidence interval [CI]=−43.3 to −22.9). The mean drooling quotient did not significantly differ between BoNT‐A treatment and bilateral submandibular duct ligation at follow‐up (3.3, p=0.457; 95% CI=−4.35 to 9.62) or between 8 and 32 weeks (4.7, p=0.188; 95% CI=−2.31 to 11.65).InterpretationBoNT‐A treatment and bilateral submandibular duct ligation are both effective treatment modalities for drooling. At 32‐week follow‐up, subjective drooling severity after bilateral submandibular duct ligation was significantly lower compared to previous BoNT‐A injections in participants. However, treatment success with BoNT‐A is no precursor to achieving success with bilateral submandibular duct ligation.What this paper adds Bilateral submandibular duct ligation is an effective therapy for drooling after treatment with botulinum neurotoxin A (BoNT‐A).Treatment success with BoNT‐A is not a predictor of successful therapy with bilateral submandibular duct ligation.

Highlights of serious distant effects after local injection of botulinum toxin therapy: A report of pediatric case

Introduction: Botulinum neurotoxin A (BoNT-A) is widely used in various conditions that cause involuntary muscle contractions, such as management of spasticity in cerebral palsy (CP). However, iatrogenic botulism resulting from systemic effects from BoNT-A is uncommon but may have serious life-threatening consequences. Case Report: We report a case of pediatric patient who developed iatrogenic botulism after therapeutic intramuscular injections of BoNT-A. Conclusion: This case highlights the importance of clinicians having adequate information of the risk of systemic botulism following local injections of BoNT-A and caution is needed in using this therapy.

Botulinum Neurotoxin-A therapy in patients with refractory overactive bladder

Aim: The aim of this study was to evaluate the clinical efficacy and safety of intravesical botulinum neurotoxin-A injection in patients with refractory overactive bladder to conservative treatment and anti-muscarinic drugs.Material and Methods: The data of 62 patients, who received botulinum neurotoxin-A (BonTA) injection (100 U) for overactive bladder (OAB) between 2015 and 2019, were reviewed retrospectively. For 55 patients included into the study, the urinary frequency and urgency, the number of incontinence and nocturia episodes, the maximum flow rate (Qmax), the post-void residual volume (PVR), and the Urinary Incontinence Quality of Life (I-QoL) scores were evaluated before the treatment and at the third month after the treatment. Results: The comparison of the pre-treatment and posttreatment 3rd-month follow-up data revealed a statistically significant decrease in the urinary frequency and urgency, and the number of incontinence and nocturia episodes (p 0.05). The mean I-QoL score increased significantly in the posttreatment 3rd month compared to the pre-treatment scores (43.62 ± 11.2 and 75.2 ± 12.6, p = 0.001, respectively). After the treatment, hematuria developed in 3 female and 2 male patients and urinary tract infections developed in 4 females and 2 male patients.Conclusion: BonTA injection significantly improves the daily urinary frequency, incontinence, and quality of life scores in patients with OAB.

The Effects of Intradetrusor BoNT-A Injections on Vesicoureteral Reflux in Children With Myelodysplasia.

PurposeWe retrospectively evaluated the efficacy of botulinum neurotoxin A (BoNT-A) on vesicoureteral reflux (VUR), continence status, and urodynamic parameters in children with myelodysplasia who were not responsive to standard conservative therapy.MethodsThe study included 31 children (13 boys, 18 girls) with a mean age of 9.2±2.3 years (range, 5–14 years) with myelodysplasia, retrospectively. All children were fully compatible with clean intermittent catheterization (CIC) and did not respond to the maximum tolerable anticholinergic dose. All children received an intradetrusor injection of 10 U/kg (maximum, 300 U) of BoNT-A into an infection-free bladder. All patients had VUR (22 unilateral, 9 bilateral) preoperatively. The grade of reflux was mild (grades 1, 2), intermediate (grade 3), and severe (grades 4, 5) in 25, 7, and 8 ureters, respectively.ResultsThe mean maximum bladder capacity increased from 152.9±76.9 mL to 243.7±103 mL (P<0.001), and the maximum detrusor pressure decreased from 57±29.4 cm H2O to 29.6±13.9 cm H2O (P<0.001). After BoNT-A treatment, 16 refluxing ureters (40%) completely resolved, 17 (42.5%) improved, 5 (12.5%) remained unchanged, and 2 (5%) became worse. Of the 31 children with urinary leakage between CICs, 22 (71%) became completely dry, 6 (19%) improved, and 3 (10%) experienced partial improvement.ConclusionsIn children with myelodysplasia, we were able to increase bladder capacity, enhance continence, and prevent VUR by using intradetrusor BoNT-A injections. Although our results are promising, a larger group of long-term prospective studies are warranted to investigate this method of treatment.

How long does the effect of botulinum toxin in neurogenic patients last? An analysis of the subset of "good responders".

The aim of this study was to assess long-term efficacity of botulinum neurotoxin A (BoNT-A) in the treatment of neurogenic detrusor overactivity (NDO). This was a retrospective monocentric study in a reference center. We included patients who received intradetrusor BoNT-A for NDO between 2001 and 2015. The focus of our analysis was on patients defined as "good responders" (≥ 5 injections of intradetrusor BoNT-A over a period of ≥5 years). The primary endpoint was the evaluation of long-term efficacity of BoNT-A. Recurrent NDO was monitored by the use of cystomanometry before the first injection and 1 month after each injection. The secondary objective was to assess the influence of NDO's etiology, age, and sex on the long-term efficacity of the treatment. A total of 107 patients were included (60.7% with spinal cord injury [SCI] and 36.4% with multiple sclerosis [MS]). The mean follow-up period was 83.7 months (66; 120). The mean number of injections was of 8.9 (5; 21). A total of 67.3% (n = 72) of patients were still controlled by treatment at the end of their follow-up period. Therapeutic failure occurred in 30 patients (26.1%) with a cessation of BoNT-A treatment at 76 months on average (median: 82.5 months). There was no significant impact of age (P = .42), sex (P = .35), or NDO's etiology (MS vs SCI; P = .54) on long-term efficacy of BoNT-A treatment. The results of our study indicate that the application of BoNT-A seems to be an effective and durable treatment in a large number of neurogenic patients after more than 10 years of follow-up. However, botulinum toxin tolerance occurred in approximately 25% of patients.

Transperineal intraprostatic injection of botulinum neurotoxin A vs transurethral resection of prostate for management of lower urinary tract symptoms secondary to benign prostate hyperplasia: A prospective randomised study

ABSTRACTObjectives: To evaluate transperineal intraprostatic injection of botulinum neurotoxin A (BoNT-A) in patients with lower urinary tract symptoms (LUTS) secondary to benign prostate hyperplasia (BPH) who failed to respond to 6-month medical treatment compared with transurethral resection of the prostate (TURP).Patients and methods: In all, 92 men were divided into TURP and BoNT-A groups after being evaluated using the International Prostate Symptom Score (IPSS) and five-item version of the International Index of Erectile Function, estimation of serum total prostate-specific antigen (tPSA), ultrasonographic estimation of prostatic volume (PV), and uroflowmetry determination of voiding volume (VV), maximum urinary flow rate (Qmax) and post-void residual urine volume (PVR). BoNT-A (200 U diluted in 3 mL saline) was injected, using a 22-G spinal needle under transrectal ultrasonography guidance, with 1-mL in each lobe. Patients were assessed 3-monthly for 12 months.Results: The IPSS significantly decreased in all patients with a non-significant difference between the groups. The mean VV and Qmax increased, whilst PVR, PV and serum tPSA significantly decreased. Patients who showed deterioration at 12 months were re-evaluated and underwent TURP. BoNT-A injection significantly maintained erectile function compared with TURP.Conclusion: Intraprostatic BoNT-A injection reduced PV with subsequent increases in VV and Qmax, and decreases in PVR and serum tPSA level. Intraprostatic BoNT-A injection allowed surgery sparing in >70% and preserved erectile function in 91.3% of patients.Abbreviations: BoNT-A: botulinum neurotoxin A; HRQOL: health-related quality of life; IIEF-5: five-item version of the International Index of Erectile Function; PV: prostatic volume; PVR: post-void residual urine volume; Qmax: maximum urinary flow rate; tPSA: total PSA; VV: voided volume