Clinical efficacy and safety analysis of type A botulinum toxin in the treatment of adolescents with refractory overactive bladder.

The objective of this study was to assess the clinical effectiveness and safety of type A botulinum toxin in the treatment of refractory overactive bladder in adolescents. We conducted a retrospective analysis of 37 adolescent patients with refractory overactive bladder who were treated at the Urology Department of Hangzhou Third People's Hospital between January 2018 and August 2023. These patients received intravesical injections of type A botulinum toxin at a concentration of 10 U/mL, with an average of 20 injection points. We recorded changes in urination diaries and urodynamic parameters both before and 1 month after treatment. After 1 month of treatment, significant improvements were observed in several parameters, when compared to the pretreatment values. These included daytime frequency of urination (11.13 ±â€…6.45), average single void volume (173.24 ±â€…36.48) mL, nighttime frequency of urination (2.43 ±â€…0.31), urgency episodes (3.12 ±â€…0.27), initial bladder capacity (149.82 ±â€…41.34) mL, and maximum bladder capacity (340.25 ±â€…57.12) mL (all P < .001). After the first treatment, 5 patients had mild hematuria, 4 patients had urinary tract infection, and 1 patient had urinary retention, which was relieved after catheterization. No serious complications or adverse reactions were observed in other patients. The follow-up period ranged from 6 to 18 months, and the duration of efficacy varied from 2 to 8 months. Eight patients who initially had treatment failure achieved symptom relief after reinjection. In adolescents with refractory overactive bladder who do not respond well to conventional drug therapy, type A botulinum toxin can be administered safely and effectively. It significantly improves lower urinary tract symptoms and enhances the quality of life for these patients.

Comparison of outcome of botulinum toxin injection with and without glyceryl trinitrate in chronic anal fissure in terms of post operative pain and healing.

Objectives: To compare the outcome of botulinum toxin injection with and without glyceryl trinitrate with respect to postoperative pain and healing in the treatment of anal fissures. METHODS: The prospective, comparative study was conducted at the Department of General Surgery, Mayo Hospital, Lahore, Pakistan, from September 1, 2021, to August 31, 2022, and comprised adult chronic anal fissure patients of either gender. They were randomised using the lottery method into group A which received botulinum toxin injection, and group B which received botulinum toxin injection plus 1g of 0.2% topical glyceryl trinitrate cream. Post-operative pain was measured 24 hours after the procedure using the visual analogue scale. Healing was assessed by examining the wound for the appearance of granulation tissue 4 weeks post-procedure. Data was analysed using SPSS 26. RESULTS: Of the 88 patients, 44(50%) were in group A; 32(72.7%) males and 12(27.3%) females with mean age 33.91±14.8 years. There were 44(50%) patients in group B; 35(79.5%) males and 9(20.5%) females with mean age range 36.33±14.9 years. The mean postoperative pain at 24 hours in group A was 4.67±1.16 and it was 3.06±0.65 in group B (p=0.009). In group A, 23(69.7%) patients showed complete healing at 4 weeks compared to 30(90.9%) in group B (p=0.030). CONCLUSIONS: Botulinum toxin injection with glyceryl trinitrate could be considered as first line of treatment for chronic anal fissure in patients who refuse surgery and with previous sphincter surgery.

Comprehensive Observational and Longitudinal study on the Outbreak of Stroke-related Spasticity focusing on the Early Onset management with Botulinum NeuroToxin (COLOSSEO-BoNT): protocol for a real-world prospective observational study on upper limb spasticity.

INTRODUCTION: Poststroke spasticity (PSS) affects up to 40% of patients who had a stroke. Botulinum neurotoxin type A (BoNT-A) has been shown to improve spasticity, but the optimal timing of its application remains unclear. While several predictors of upper limb PSS are known, their utility in clinical practice in relation to BoNT-A treatment has yet to be fully elucidated. The COLOSSEO-BoNT study aims to investigate predictors of PSS and the effects of BoNT-A timing on spasticity-related metrics in a real-world setting. METHODS AND ANALYSIS: The recruitment will involve approximately 960 patients who have recently experienced an ischaemic stroke (within 10 days, V0) and will follow them up for 24 months. Parameters will be gathered at specific intervals: (V1) 4, (V2) 8, (V3) 12, (V4) 18 months and (V5) 24 months following enrolment. Patients will be monitored throughout their rehabilitation and outpatient clinic journeys and will be compared based on their BoNT-A treatment status-distinguishing between patients receiving treatment at different timings and those who undergo rehabilitation without treatment. Potential predictors will encompass the Fugl-Meyer assessment, the National Institute of Health Stroke Scale (NIHSS), stroke radiological characteristics, performance status, therapies and access to patient care pathways. Outcomes will evaluate muscle stiffness using the modified Ashworth scale and passive range of motion, along with measures of quality of life, pain, and functionality. ETHICS AND DISSEMINATION: This study underwent review and approval by the Ethics Committee of the Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy. Regardless of the outcome, the findings will be disseminated through publication in peer-reviewed journals and presentations at national and international conferences. TRIAL REGISTRATION NUMBER: NCT05379413.

A Systematic Review of Botulinum Toxin Injection in Pediatric Dystonia.

Botulinum toxin (BT), a first-line treatment for focal dystonias in adults, has gained USA Food and Drug Administration approval for pediatric upper and lower extremity spasticity and sialorrhea, though its use in children younger than 2 years old is still considered off-label treatment for all pathologies. Dosing, treatment strategies and outcome measures lack international consensus, and they are often extrapolated from adult or spasticity guidelines. This review aims to evaluate the best available evidence on the efficacy and safety of BT therapy in pediatric dystonia (age under 21 years old), isolated or associated with other medical conditions. A comprehensive search in PubMed, Scopus and Web of Science was conducted, including only articles in English. Although no randomized controlled trials are still present, 12 articles were included with an overall of 57 patients. All the papers demonstrate that BT can improve motor function, decrease pain and ameliorate quality of life, with minimal adverse effects in pediatric patients affected by pure or mixed dystonic motor disorders. Despite the low level of evidence, our review shows that BT could be an efficacious treatment for these pediatric patients. The frequent generalized involvement, together with the heterogeneous nature of childhood dystonic forms, sometimes intermingled with spasticity, prompts further multicenter clinical trials or prospective studies with a higher level of evidence to shed light on the efficacy and safety profile of BT in pediatric dystonia.

Long-Term Adherence to Onabotulinum Toxin-A Intradetrusor Injections for Neurogenic Dysfunction in Children-A Retrospective Single-Center Evaluation.

Onabotulinum Toxin-A (BTX-A) is a second-line treatment for neurogenic bladder (NB). It requires repeated injections over time, which is a possible limit for long-term adherence, especially in children, as general anesthesia is required. Almost 50% of adults discontinue therapy; few data on pediatric patients are present. The aim of this study is to share our long-term experience of BTX-A adherence in children. This study is a retrospective review of 230 refractory NB patients treated with BTX-A. The inclusion criteria were ≥3 treatments and the first injection performed ≥10 years before the study endpoint. Fifty-four patients were included. Mean follow-up was 10.2 years; mean treatment number was 6.4 for each patient. During follow-up, 7% did not need BTX-A anymore; 76% discontinued therapy, with a prevalence of acquired NB (64% acquired vs. 34% congenital; p = 0.03); sex-based and urodynamic findings did not influence the discontinuation rate (p = 0.6, p = 0.2, respectively). Considering those who withdrew from the therapy, 43% were lost to follow-up/died after a mean of 7.5 years (although 33% still experienced clinical efficacy); 33% changed therapy after a mean of 5.8 years (with reduced efficacy in 22%, persistent efficacy in 11%). BTX-A is a safe and effective therapy for pediatric patients. The treatment abandonment rate is higher for children than for adults; no specific reasons were highlighted. It is necessary to evaluate any age-specific factors to explain these data.

Understanding Clinical Effectiveness and Safety Implications of Botulinum Toxin in Children: A Narrative Review of the Literature.

Since its first approval by the Food and Drug Administration in 1989 for strabismus, botulinum toxin indications of use have been widely expanded. Due to its anticholinergic properties, this toxin is currently approved in adult patients for the treatment of a wide range of neuromuscular, otolaryngologic, orthopedic, gastrointestinal, and urologic disorders. Approved pediatric indications of use include the treatment of blepharospasm associated with dystonia, strabismus, lower-limb spasticity, focal spasticity in patients with cerebral palsy, and neurogenic detrusor overactivity. Alongside these approved indications, botulinum toxin is extensively used off-label. Although several clinical studies have shown that botulinum toxin is effective and well-tolerated in children, uncertainties persist regarding its long-term effects on growth and appropriate dosing in this population. As such, further research is needed to better define the botulinum toxin risk-benefit profile and expand approved uses in pediatrics. This narrative review aimed to provide a broad overview of the evidence concerning the clinical effectiveness and safety of BoNT with respect to its principal authorized and non-authorized pediatric therapeutic indications, as well as to describe perspectives on its future use in children.

Onabotulinumtoxina in the Prevention of Migraine in Pediatric Population: A Systematic Review.

Migraine is a leading cause of disability worldwide, yet it remains underrecognized and undertreated, especially in the pediatric and adolescent population. Chronic migraine occurs approximately in 1% of children and adolescents requiring preventive treatment. Topiramate is the only FDA-approved preventative treatment for children older than 12 years of age, but there is conflicting evidence regarding its efficacy. OnabotulinumtoxinA is a known and approved treatment for the management of chronic migraine in people older than 18 years. Several studies examine its role in the pediatric population with positive results; however, the clear-cut benefit is still unclear. OnabotulinumtoxinA seems not only to improve disability scores (PedMIDAS) but also to improve the quality, characteristics, and frequency of migraines in the said population. This systematic review aims to summarize the evidence on the efficacy, dosing, administration, long-term outcomes, and safety of onabotulinumtoxinA in pediatric and adolescent migraine. Eighteen studies met the eligibility criteria and were included in this review. The mean monthly migraine days (MMDs), decreased from of 21.2 days per month to 10.7 after treatment. The reported treatment-related adverse effects were mild and primarily injection site related and ranged from 0% to 47.0%. Thus, this review provides compelling evidence suggesting that OnabotulinumtoxinA may represent a safe and effective preventive treatment option for pediatric migraine.

Clinical Conditions Targeted by OnabotulinumtoxinA in Different Ways in Medicine.

OnabotulinumtoxinA (BT-A) is used in different medical fields for its beneficial effects. BT-A, a toxin originally produced by the bacterium Clostridium botulinum, is widely known for its ability to temporarily paralyze muscles by blocking the release of acetylcholine, a neurotransmitter involved in muscle contraction. The literature continually reports new hypotheses regarding potential applications that do not consider blockade of acetylcholine release at the neuromuscular junction as a common pathway. In this opinion article, it is our aim to investigate the different pathway targets of BT-A in different medical applications. First of all, the acetylcholine effect of BT-A is used to reduce wrinkles for cosmetic purposes, in the treatment of urological problems, excessive sweating, temporomandibular joint disorders, obesity, migraine, spasticity in neurological diseases, and in various cases of muscle overactivity such as cervical dystonia, blepharospasm, and essential head tremor. In another potential pathway, glutamate A, CGRP, and substance P are targeted for pain inhibition with BT-A application in conditions such as migraine, trigeminal neuralgia, neuropathic pain, and myofascial pain syndrome. On the other hand, as a mechanism different from acetylcholine and pain mediators, BT-A is used in the treatment of hair loss by increasing oxygenation and targeting transforming growth factor-beta 1 cells. In addition, the effect of BT-A on the apoptosis of cancer cells is also known and is being developed. The benefits of BT-A applied in different doses to different regions for different medical purposes are shown in literature studies, and it is also emphasized in those studies that repeating the applications increases the benefits in the long term. The use of BT-A continues to expand as researchers discover new potential therapeutic uses for this versatile toxin.

Gait Reconstruction Strategy Using Botulinum Toxin Therapy Combined with Rehabilitation.

Numerous studies have established a robust body of evidence for botulinum toxin A (BoNT-A) therapy as a treatment for upper motor neuron syndrome. These studies demonstrated improvements in spasticity, range of joint motion, and pain reduction. However, there are few studies that have focused on improvement of paralysis or functional enhancement as the primary outcome. This paper discusses the multifaceted aspects of spasticity assessment, administration, and rehabilitation with the goal of optimising the effects of BoNT-A on lower-limb spasticity and achieving functional improvement and gait reconstruction. This paper extracts studies on BoNT-A and rehabilitation for the lower limbs and provides new knowledge obtained from them. From these discussion,, key points in a walking reconstruction strategy through the combined use of BoNT-A and rehabilitation include: (1) injection techniques based on the identification of appropriate muscles through proper evaluation; (2) combined with rehabilitation; (3) effective spasticity control; (4) improvement in ankle joint range of motion; (5) promotion of a forward gait pattern; (6) adjustment of orthotics; and (7) maintenance of the effects through frequent BoNT-A administration. Based on these key points, the degree of muscle fibrosis and preintervention walking speed may serve as indicators for treatment strategies. With the accumulation of recent studies, a study focusing on walking functions is needed. As a result, it is suggested that BoNT-A treatment for lower limb spasticity should be established not just as a treatment for spasticity but also as a therapeutic strategy in the field of neurorehabilitation aimed at improving walking function.

[Treatment of bruxism with botulinum toxin: think twice!] / Behandeling van bruxisme met botulinetoxine: bezint eer ge begint!

A recent publication in the Nederlands Tijdschrift Voor Tandheelkunde (Dutch Journal of Dentistry) suggests botulinum toxin as a primary treatment for bruxism, especially for severe complaints of teeth grinding or jaw clenching. However, in the opinion of Lobbezoo et al., some outdated views on bruxism are used, and botulinum toxin is incorrectly classified as safe, according to them. In this Vision article, the authors describe the current insights into bruxism; they indicate how the presence of bruxism can be assessed in the clinic; when and how bruxism is treated; and finally, what the role of botulinum toxin is: an ultimum refugium. Therefore, regarding the use of botulinum toxin within the discipline of orofacial pain and dysfunction Lobbezoo et al. recommend: think twice!

Exploring botulinum toxin's impact on masseter hypertrophy: a randomized, triple-blinded clinical trial.

The present study aimed to assess the effectiveness and functional adverse effects of a single and multiple injections of botulinum toxin A (BoNT-A) for masseter hypertrophy (MH). Twenty-six women complaining about lower third facial enlargement due to MH, received 75 U of BoNT-A (abobotulinum toxin) in each masseter muscles. After 3 months, patients were randomly assigned to receive a second treatment session of Saline Solution: (G1; n = 11) or BoNT-A: (G2; n = 12). Muscle thickness (ultrasound), electrical activity (electromyography; EMG), masticatory performance, and subjective perception of MH were evaluated. Follow-up was performed at 1, 3 and 6 months. Muscle thickness, EMG activity, and masticatory performance were analyzed using ANOVA two-way and Sidak test as post-hoc. Masticatory performance was analyzed by the Friedman's test and Mann-Whitney test. Regarding inter-groups comparisons, there was a significant decrease in the left masseter muscle thickness in the G2 group at the 6 month follow-up (p < 0.02). For EMG, significant differences were evident at the 6 month assessment, with higher masseter activity for G1 (p < 0.05). For masticatory performance, no significant differences were observed throughout the study (p > 0.05) and a higher improvement in subjective perception of MH was observed in the 1 month follow-up for G2 (p < 0.05). In conclusion, BoNT-A is effective for MH, however multiple injections cause functional adverse effects in masseter muscle.

Concomitant Botulinum Toxin Injections for Neurogenic Detrusor Overactivity and Spasticity-A Retrospective Analysis of Practice and Safety.

As multiple indications for botulinum toxin injections (BTIs) can coexist for neurological patients, there are to date no description of concomitant injections (CIs) to treat both spasticity and neurogenic detrusor overactivity incontinence (NDOI) in patients with spinal cord injuries (SCIs) and multiple sclerosis (MS). We therefore identified patients followed at our institution by health data hub digging, using a specific procedure coding system in use in France, who have been treated at least once with detrusor and skeletal muscle BTIs within the same 1-month period, over the past 5 years (2017-2021). We analyzed 72 patients representing 319 CIs. Fifty (69%) were male, and the patients were mostly SCI (76%) and MS (18%) patients and were treated by a mean number of CIs of 4.4 ± 3.6 [1-14]. The mean cumulative dose was 442.1 ± 98.8 U, and 95% of CIs were performed within a 72 h timeframe. Among all CIs, five patients had symptoms evocative of distant spread but only one had a confirmed pathological jitter in single-fiber EMG. Eleven discontinued CIs for surgical alternatives: enterocystoplasty (five), tenotomy (three), intrathecal baclofen (two) and neurotomy (one). Concomitant BTIs for treating both spasticity and NDOI at the same time appeared safe when performed within a short delay and in compliance with actual knowledge for maximum doses.

Long-Term Enhancement of Botulinum Toxin Injections for Post-Stroke Spasticity by Use of Stretching Exercises-A Randomized Controlled Trial.

Botulinum toxin A (BONT/A) injections play a central role in the treatment of upper limb spasticity in stroke patients. We proposed structured stretching exercises to enhance the effect of post-stroke spasticity relief of the upper limbs following BONT/A injections. A total of 43 patients who had a stroke with grade 2 spasticity or higher on the Modified Ashworth Scale (MAS) in their upper-limb muscles were randomly assigned to the intervention (n = 21) or control group (n = 22). The former received structured stretching exercises after their BONT/A injections for 20 min, 5 days per week, for 6 months at a hospital, while the others conducted self-stretching exercises at home. The outcome measures were assessed before the intervention (T0) and after three (T1) and six months (T2). Significantly greater improvements in the MAS scores of the elbows, wrists, and fingers were found in the intervention group's patients at T1 and T2. The behavioral outcome measures, including shoulder pain, activities of daily living, and quality of life, and our electrophysiological studies also showed a significantly higher enhancement in this patient group. In conclusion, the structured stretching exercises plus BONT/A injections for six months showed a superior effect in relieving post-stroke upper-limb spasticity compared to self-stretching exercises.

Effectiveness of repeated injections of botulinum toxin A on gait and fatigue in adults with spastic paraparesis secondary to multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is the most common neurologic disease in young adults. Spasticity is one of its most disabling symptoms, with botulinum toxin A type A (BoNT-A) being one of the treatments of choice for this symptom. OBJECTIVE: We assessed the response to abobotulinumtoxinA in improving walking ability and fatigue in patients with spastic paraparesis caused by MS. METHODS: We performed a real-world, multicenter, prospective, open-label low-intervention trial in 84 patients with MS and spastic paraparesis of the lower limbs infiltrated with abobotulinumtoxinA (LINITOX study). The response of spasticity, walking ability and fatigue is analyzed in 4 cycles of ultrasound-guided injection in the lower limbs. RESULTS: The patients improved their walking ability by an average of 11.34% meters measured with 6-Minute Walk Test (6MWT), and decreased the percentage of fatigue by 6.86% (4.66 percentage points less), in the 12-Item Multiple Sclerosis Walking Scale (MSWS-12) 4 weeks after abobotulinumtoxinA injection, both values are statistically significant. This improvement seems to persist over time, throughout the cycles. CONCLUSION: We found improved walking ability and less fatigue in patients with MS-related spastic paresis of the lower limbs after injection of abobotulinumtoxinA.

[Botulinum toxin A for idiopathic overactive bladder in women]. / Botulinumtoxin A bei idiopathischer Blasenüberaktivität (iOAB) der Frau.

Following a description of the historic evolution of botulinum toxin A detrusor injections for neurogenic and nonneurogenic bladder overactivity, which was mainly driven by German-speaking countries, the terminological revolution of 2002 and the influence on design and outcomes of upcoming approval studies for the indication overactive bladder (OAB) are examined. OnabotulinumtoxinA (100 IU) for second-line treatment of OAB received European approval in 2013. Phase IV observational studies concerning therapeutic persistence and adherence with onabotulinumtoxinA are analyzed and compared with therapeutic alternatives. Predictors of treatment success and complications are identified and compared to the required preinterventional diagnostic effort. Since onabotulinumtoxinA and sacral neuromodulation (SNM) are competing for second-line OAB treatment, both options are compared with regard to differential indications, effectivity, durability and patient adherence. Gender-specific causes of urgency and urge incontinence in women are differentiated from the diagnosis of OAB and require priority treatment. On the basis of diagnostic examination results, an algorithm for invasive second-line treatment of OAB is presented, since overly liberal utilization of onabotulinumtoxinA in therapy-naive OAB patients has not proven superiority over oral antimuscarinergic standard therapy, which can only be explained by improper patient selection.

Mobile digital gait analysis captures effects of botulinum toxin in hereditary spastic paraplegia.

BACKGROUND AND PURPOSE: Hereditary spastic paraplegias (HSPs) comprise a group of inherited neurodegenerative disorders characterized by progressive spasticity and weakness. Botulinum toxin has been approved for lower limb spasticity following stroke and cerebral palsy, but its effects in HSPs remain underexplored. We aimed to characterize the effects of botulinum toxin on clinical, gait, and patient-reported outcomes in HSP patients and explore the potential of mobile digital gait analysis to monitor treatment effects and predict treatment response. METHODS: We conducted a prospective, observational, multicenter study involving ambulatory HSP patients treated with botulinum toxin tailored to individual goals. Comparing data at baseline, after 1 month, and after 3 months, treatment response was assessed using clinical parameters, goal attainment scaling, and mobile digital gait analysis. Machine learning algorithms were used for predicting individual goal attainment based on baseline parameters. RESULTS: A total of 56 patients were enrolled. Despite the heterogeneity of treatment goals and targeted muscles, botulinum toxin led to a significant improvement in specific clinical parameters and an improvement in specific gait characteristics, peaking at the 1-month and declining by the 3-month follow-up. Significant correlations were identified between gait parameters and clinical scores. With a mean balanced accuracy of 66%, machine learning algorithms identified important denominators to predict treatment response. CONCLUSIONS: Our study provides evidence supporting the beneficial effects of botulinum toxin in HSP when applied according to individual treatment goals. The use of mobile digital gait analysis and machine learning represents a novel approach for monitoring treatment effects and predicting treatment response.