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Objectives: Evaluating the effectiveness and safety of repeated high-dose intradetrusor abobotulinumtoxin A (Dysport®) injections for the treatment of pediatric neurogenic bladders refractory to medications., Design: Retrospective interventional study., Participants: The cohort included 37 children (22 boys and 15 girls) of median age 9.2 years. Inclusion criteria were diagnosis of neurogenic bladder and failure to respond to medical treatment. Exclusion criteria were augmented bladder, insufficient data, and interval of > 11 months between video-urodynamic study and Dysport injection., Interventions: All participants were treated with an intra-detrusor injection of Dysport 30 IU/kg (up to 1000 IU) under general anesthesia. Repeated (second and third) injections were scheduled (6-12 months) in patients who demonstrated an improvement in cystometric parameters. All participants underwent video urodynamic testing before onset of treatment and 4-5 months after subsequent injection., Main Outcome Measures: Success of treatment was defined as a decrease in end filling pressure (EFP) to < 40 cm H 2 O and/or a 20% increase in maximal cystometric capacity (MCC). These parameters along with initial bladder features were evaluated for ability to predict treatment success., Results: No side effects of Dysport were observed or reported. The overall success rate was 62%. MCC increased by a median of 30% (IQR 200-300, p < 0.001), 37% (IQR 197-310, p = 0.001) and 45% (IQR 245-300, p = 0.025) after the first, second and third injections, respectively. Median EFP decreased from 45 cm H 2 O to 34 cm H 2 O (IQR 20-45, p = 0.029), 23 cm H 2 O (IQR 20-37, p = 0.004), and 20 cm H 2 O (IQR 12-32, p = 0.049) after the first, second, and third injections, respectively. No predicting factor of success of treatment were found; However, three of five cases of "end stage" bladder showed improvement., Conclusions: High-dose Dysport injection is safe and effective for the treatment of neurogenic bladder. Studies with larger cohort and a control group would further elucidate which bladders would benefit most. At present, we recommend treating also bladders with "end stage" features with botulinum toxin before considering augmentation., (© 2024 The Author(s). Neurourology and Urodynamics published by Wiley Periodicals LLC.)

Background: This pooled analysis of randomized controlled studies investigated the safety and efficacy of onabotulinumtoxinA in male and female patients with overactive bladder (OAB)., Methods: Data were pooled from four similarly designed trials in North America and Europe. Adults with idiopathic OAB for ≥6 months inadequately managed by at least one anticholinergic were randomized 1:1 or 2:1 to receive onabotulinumtoxinA 100 U or matched placebo in Cycle 1 and could request open-label retreatment with onabotulinumtoxinA 100 U at ≥12 weeks. Efficacy outcomes at Week 12 included the primary endpoint of mean urinary incontinence (UI) episodes per day and other variables, such as the proportion of patients with ≥50% reduction in daily UI episodes. Safety was assessed by monitoring treatment-emergent adverse events (TEAEs). Analyses by sex were descriptive. Males were further analyzed by benign prostatic hyperplasia (BPH) diagnosis status., Results: In the pooled population (N = 1564), there were 194 males (12.4%) and 1370 females (87.6%). Mean number of baseline UI episodes per day was 4.9 in males and 5.5 in females. At Week 12, numerically greater mean reductions from baseline in number of daily UI episodes were observed with the onabotulinumtoxinA 100 U group (females: -3.0; males: -2.2) versus placebo (females: -1.1; males: -1.3). Achievement of ≥50% reduction in daily UI episodes was numerically greater with onabotulinumtoxinA 100 U (females: 64.8%; males: 61.2%) versus placebo (females: 30.6%; males: 44.8%), and numerically higher in males without BPH (onabotulinumtoxinA: 65.1%; placebo: 50.9%) versus with BPH (onabotulinumtoxinA: 54.3%; placebo: 36.6%). A total of 34.7% of males and 39.4% of females experienced at least one TEAE in the first 12 weeks during treatment Cycle 1. Urinary tract infection rate was 13.1% in females and 4.2% in males; incidence of hematuria was 6.8% in males and 1.1% in females. Incidence of urinary retention (defined as incomplete emptying, requiring catheterization) was 2.7% in females and 4.7% in males., Conclusion: OnabotulinumtoxinA 100 U was efficacious and well tolerated in men and women with OAB, including in males with and without BPH. No new safety findings were identified when data were analyzed by sex., (© 2024 The Author(s). Neurourology and Urodynamics published by Wiley Periodicals LLC.)

Crow's feet lines in the lateral canthal region are a common concern among aging patients, initially appearing as dynamic wrinkles during facial expressions and becoming more pronounced with age. Botulinum neurotoxin temporarily paralyzes muscles by inhibiting acetylcholine release, smoothing wrinkles and enhancing skin's youthful appearance. Effective treatment requires tailored approaches considering individual anatomy and muscle activity. Recent cadaveric studies identified the tear trough muscle, emphasizing its role in infraorbital support and aging. Clinically, patients often present medial eye wrinkles after BoNT treatment for crow's feet, prompting exploration of underlying mechanisms and management strategies. Three cases demonstrated that medial BoNT injections in the orbicularis oculi muscle significantly improve medial eye wrinkles and tear trough appearance. The study underscores the importance of understanding muscle hyperactivity and anatomical variations for precise treatment. Enhanced injection techniques targeting specific areas can achieve better outcomes and minimize complications, particularly in culturally sensitive regions where facial expressions are valued. This research highlights the necessity for comprehensive anatomical knowledge and patient-specific treatment strategies to address medial eye wrinkles effectively., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: Interstitial cystitis (IC)/bladder pain syndrome (BPS) is an unpleasant sensation related to the bladder with lower urinary tract symptoms lasting more than 6 weeks, unrelated to an otherwise identifiable cause. The etiology is likely multifactorial including urothelial abnormalities, neurogenic pain upregulation, and potentially bladder and vaginal microbiome alterations. Despite treatment effectiveness of both bladder instillations and intradetrusor onabotulinumtoxinA injection for this condition, a head-to-head comparison has not been performed., Objective: To compare the efficacy of bladder instillations and intradetrusor onabotulinumtoxinA injection for treatment of IC/BPS., Study Design: Patients with O'Leary-Sant (OLS) questionnaire scores of ≥6, meeting clinical criteria for IC/BPS, and desiring procedural management were randomized to bladder instillations or intradetrusor onabotulinumtoxinA injection. The primary outcome was the difference in OLS scores at 2 months posttreatment between groups. Secondary outcomes included evaluation of sexual function, physical/mental health status, pain, patient satisfaction, treatment perception, retreatment, and adverse event rates., Results: Forty-seven patients were analyzed with 22 randomized to bladder instillations and 25 to onabotulinumtoxinA injection. There were no differences in demographic and clinical characteristics between groups. From baseline to 2 months posttreatment, there was a decrease in OLS subscales in all patients (Interstitial Cystitis Symptom Index [ICSI] -6.3 (confidence interval [CI] -8.54, -3.95), P<.0001; Interstitial Cystitis Problem Index [ICPI] -5.9 (CI -8.18, -3.57), P<.0001). At 2 months posttreatment, patients in the onabotulinumtoxinA group had significantly lower OLS scores compared to those in the bladder instillation group (ICSI 6.3±4.5 [onabotulinumtoxinA] vs 9.6±4.2 [instillation], P=.008; ICPI 5.9±5.1 [onabotulinumtoxinA] vs 8.3±4.0 [instillation], P=.048). The difference in OLS scores between groups did not persist at 6 to 9 months posttreatment. There were no statistically significant differences between baseline and posttreatment time points for the remaining questionnaires. Eight percent of patients who received onabotulinumtoxinA injection experienced urinary retention requiring self-catheterization. Patients who underwent onabotulinumtoxinA injection were significantly less likely to receive retreatment within 6 to 9 months compared to patients who received bladder instillations (relative risk 13.6; 95% CI, 1.92-96.6; P=.0002). There were no differences between groups regarding patient satisfaction, perception of treatment convenience, or willingness to undergo retreatment., Conclusion: Both onabotulinumtoxinA injection and bladder instillations are safe, effective treatments for patients with IC/BPS, with significant clinical improvement demonstrated at 2 months posttreatment. Our findings suggest that intradetrusor onabotulinumtoxinA injection is a more effective procedural treatment for this condition than bladder instillation therapy and associated with decreased rates of retreatment., (Published by Elsevier Inc.)

Objectives: To report the efficacy of onabotulinumtoxinA (BoNTA) injections in relieving pain in patients with primary trochlear headache (PRTH)., Methods: Examination of medical records for patients diagnosed with PRTH according to the International Classification of Headache Disorders, 3rd edition criteria and treated with BoNTA. Data were collected for variables related to pain relief, duration of effectiveness, and adverse effects., Results: Six patients were included in the study. All had previously undergone standard care interventions, including infiltrations or oral treatments, yet experienced treatment failure or symptom recurrence. All patients received 20 units of BoNTA, administered in the corrugator and procerus muscles. Subsequent to the BoNTA injections, all six patients reported substantial pain relief, with five achieving complete remission of symptoms. The analgesic effect persisted for a duration of 3 months. No adverse events were reported in any of the cases., Conclusions: Our case series presents the first evidence of the potential of BoNTA as a safe and effective treatment option for PRTH. From a clinical standpoint, having a safer alternative is of paramount significance for patients with limited treatment options, such as those with PRTH. Further research is warranted to validate these findings and explore the long-term efficacy of BoNTA in PRTH management., (© 2024 The Authors. Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.)

Intradermal injection of botulinum neurotoxin is a frequently performed procedure in aesthetic dermatology to improve facial skin tone, texture, fine wrinkles, and enlarged pores. In practice, botulinum neurotoxin type A is also used to reduce skin oiliness of the face. There is increasing evidence that acetylcholine plays specific roles in sebum production, suggesting that botulinum neurotoxin type A may reduce sebum production by interfering with cholinergic transmission between sebaceous glands and autonomic nerve terminals. Botulinum neurotoxins can also inhibit several pathogenetic components of acne development, suggesting that botulinum neurotoxins can be used as a safe and effective treatment modality for acne and other skin disorders related to overactivity of sebaceous glands. This review aims to explore the current evidence behind the treatment of facial seborrhea and acne with botulinum neurotoxin type A.

Various types of botulinum toxin (BoNT) have been studied to treat cervical dystonia (CD). Although high-dose BoNT has proven efficacy, it increases the risk of adverse events. For this reason, this study was planned to identify the non-inferiority efficacy, tolerability, and safety of low-dose neubotulinum toxin A (Neu-BoNT-A) versus low-dose abobotulinum toxin A (Abo-BoNT-A) in CD treatment. The 48-week, prospective, randomized, controlled crossover design study of CD treatment, with 50-unit Neu-BoNT-A and 250-unit Abo-BoNT-A injections at 12-week intervals, was conducted over a 24-week treatment period. This study used the following standardized rating scales to assess the efficacy of BoNT: the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS); health-related quality of life (HRQoL); the Cervical Dystonia Impact Profile (CDIP-58); the Short Form 36 health survey questionnaire (SF-36); and, for the depressive symptoms of CD patients, the Center for Epidemiological Studies-Depression Scale (CES-D) and the Patient Health Questionnaire-9 (PHQ-9). Fifty-two CD patients were enrolled from October 2019 to January 2021. The mean scores of the TWSTRS total at the post-treatments in both Neu-BoNT-A and Abo-BoNT-A had a significant reduction from baseline ( p = 0.008 and 0.002, respectively). However, the mean changes of the TWSTRS total at the 12- and 24-week treatments between the two treatment groups were not significantly different ( p = 0.284 and 0.129, respectively). The mean scores of the HRQoL questionnaires (the CIDP-58 and the SF-36) and the depressive symptoms (the CES-D and the PHQ-9) in both treated groups at the post-treatments did not significantly decrease from baseline and were comparable. Two patients treated with Abo-BoNT-A (250 units) reported cervical tension and benign paroxysmal positional vertigo (BPPV). There were no serious adverse events reported. Though both low-dose BoNT-As were effective at improving clinical symptoms without significant side effects, both treatments did not predict change in quality of life and depression. With the non-inferiority criteria, low-dose Neu-BoNT-A has a similar efficacy, safety, and tolerability to Abo-BoNT-A.

The presence of severe Raynaud's Phenomenon (RP), with permanent pain or digital necrosis is a rare condition. Cervical sympathectomy or distal sympathectomy or A botulinum toxin have demonstrated efficacy after medical treatment failure. We report the case of a 38-year-old female patient with an acute onset of severe RP in both hands secondary to systemic sclerosis. Medical treatment failed, so a novel approach by a combination of a modified distal sympathectomy and injection of A botulinum toxin on digital neuromuscular bundles was performed. Remission of the pain occurred immediately after the procedure and 45 days later she had complete healing of the digital wounds and recovered full mobilization of both hands. The patient remained asymptomatic 6 month after the procedure, and a Doppler ultrasound showed tri-phasic flows distal to the surgical site. This novel technique is described, and a brief review of the literature is performed.

Botulinum toxin (BT) injections into the cervical muscles are an effective and commonly practiced treatment approach for cervical dystonia. In this retrospective longitudinal study, we collected data from the Sheba electronic medical records on consecutive patients with idiopathic cervical dystonia (ICD), treated regularly with periodic BT injections between the years 2008-2020. All treatment visits were analyzed regarding type of toxin, dose injected, and clinical outcomes. The vast majority of patients were treated with abobotulinum toxin A. Sixty-four ICD patients (51 (79.7%) females, onset at age 45.8 ± 13.7 years) were treated over 17.1 ± 13.9 (range 3 to 49) visits per patient; BT treatment efficacy increased gradually from initial treatment sessions to visit 13, when it achieved a steady state. While the subjective report of percentage improvement and its duration were around 78.9 ± 17.1% for 2.8 ± 1.0 months, respectively, the dose of BT increased significantly over the years (p = 0.006). Side effects (SE) were not rare, and commonly recurred after subsequent sessions and were usually mild and short-lasting, with dysphagia being the most common (~17.5%), followed by neck/arm weakness (11.9%) and cervical pain (8.9%). Repeated injections of BT for ICD remain beneficial for patients over several years of therapy, and despite mild SE, patients tend to adhere to a 3-4 months interval schedule., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Anal fissure is one of the most common benign anal disorders, and medical treatments play an important role in its management., Objective: The purpose of this study was to investigate the short-term effects and success of platelet-rich plasma in the treatment of chronic anal fissure., Design: The study is a 2 parallel group, randomized, controlled clinical trial., Settings: The study was performed in 2 tertiary university hospitals., Patients: Forty-four patients with chronic anal fissure were randomly assigned to platelet-rich plasma treatment or control group. Presenting symptoms and pain scores were recorded on enrollment. The control patient self-administered topical glyceryl trinitrate. Platelet-rich plasma was injected locally in the intervention group followed by self-administered glyceryl trinitrate., Main Outcome Measures: The primary outcome measure is a reduction in pain scores., Results: On day 10 and 1 month after treatment, the mean pain score was significantly lower in the patients treated with platelet-rich plasma than in the controls (p = 0.005 and p < 0.005). By 1 month after treatment, the mean pain score declined by 5.7 points in the platelet-rich plasma-treated group compared with a 4.1 mean pain score decline in the control group (mean difference:1.6 points (95% CI, 0.3-2.9)). According to the repeated-measures analyses, pain scores decreased in both groups, but the decrease in the treatment group was statistically higher than in the control group (p < 0.001). Complete epithelialization and recovery rates were significantly higher in the platelet-rich plasma group than in controls at all follow-up times, with p values ranging from 0.034 to <0.001. The observed difference in complete epithelialization after 2 months of treatment between the platelet-rich plasma group and the control group was 56.2% with a 95% CI of 14.03% to 98.4%., Limitations: This study was limited by its small sample size, and long-term follow-up of the patients was not presented., Conclusions: Platelet-rich plasma reduced concerns and accelerated epithelialization and healing in patients with chronic anal fissures. See Video Abstract at http://links.lww.com/DCR/B461.RESULTADOS A CORTO PLAZO DEL PLASMA RICO EN PLAQUETAS EN EL TRATAMIENTO DE LA FISURA ANAL CRÓNICA: ESTUDIO CLÍNICO CONTROLADO ALEATORIZADO., Antecedentes: La fisura anal es uno de los trastornos anales benignos más comunes y los tratamientos médicos juegan un papel importante en su manejo., Objetivo: El propósito de este estudio fue investigar los efectos a corto plazo y el éxito del plasma rico en plaquetas en el tratamiento de la fisura an33al crónica., Diseo: El estudio es un ensayo clínico controlado, aleatorizado y de dos grupos paralelos., Escenario: El estudio se llevó a cabo en dos hospitales universitarios terciarios., Pacientes: Cuarenta y cuatro pacientes con fisura anal crónica fueron asignados aleatoriamente al grupo de tratamiento con plasma rico en plaquetas o al grupo control. Los síntomas de presentación y las puntuaciones de dolor se registraron en la inscripción. Los pacientes de control se autoadministraron trinitrato de glicerilo tópico. El plasma rico en plaquetas se inyectó localmente en el grupo de intervención seguido de trinitrato de glicerilo autoadministrado., Principales Medidas De Resultado: La principal medida de resultado es una reducción en las puntuaciones de dolor., Resultados: El día 10 y un mes después del tratamiento, la puntuación media de dolor fue significativamente menor en los pacientes con plasma rico en plaquetas que en los controles (p = 0.005 y p <0.005, respectivamente). Un mes después del tratamiento, la puntuación media de dolor disminuyó 5.7 puntos en el grupo tratado con plasma rico en plaquetas en comparación con una disminución de la puntuación media de dolor de 4.1 en el grupo de control (diferencia media: 1.6 puntos [intervalo de confianza del 95%; 0.3-2.9] Según los análisis de medidas repetidas, las puntuaciones de dolor disminuyeron en ambos grupos, pero la disminución en el grupo de tratamiento fue estadísticamente mayor que en el grupo de control (p <0.001). Las tasas de epitelización completa y recuperación fueron significativamente más altas en los pacientes con plasma rico en plaquetas que en los controles en todos los tiempos de seguimiento, con valores de p que van desde 0.034 a <0.001. La diferencia observada en la epitelización completa después de dos meses de tratamiento entre el grupo de plasma rico en plaquetas y el grupo de control fue del 56.2% con un intervalo de confianza del 95% del 14.03% al 98.4%., Limitaciones: Este estudio estuvo limitado por el pequeño tamaño de la muestra y porque no se proporcionó un seguimiento a largo plazo de los pacientes., Conclusiones: El plasma rico en plaquetas redujo las molestias y aceleró la epitelización y la curación en pacientes con fisuras anales crónicas. Consulte Video Resumen en http://links.lww.com/DCR/B461. (Traducción-Dr. Jorge Silva Velazco)., (Copyright © The ASCRS 2021.)

Introduction: Botulinum toxin (BoNT) injections represent the gold standard treatment for cervical dystonia (CD). Different types of BoNT have been used for the treatment of CD, but only two serotypes, BoNT type A (BoNT-A) and type B (BoNT-B), have been approved by regulatory agencies. Efficacy and safety of BoNT have been well documented by many short-term studies, but the longterm effects have been investigated only relatively recently. Areas covered: In the present review, we aimed to critically reappraise the existing evidence on the long-term efficacy and safety of BoNT treatment in CD. The examined studies mainly explored BoNT-A serotypes. Only a few studies examined the long-term effects of BoNT-B serotypes, and only one head-to-head comparison between BoNT-A and BoNT-B was found. BoNT was consistently reported to be an effective and safe treatment for CD patients, with good outcomes and a few adverse events in the long-term. However about a third of patients still drop out from the treatment during a long-term follow-up. Expert opinion: We conclude that BoNT is safe and effective in the long-term treatment of patients with CD. Additional studies are needed to further explore patients real-life experiences and perspectives to better understand the long-term outcomes and reasons for discontinuation of treatment.

Botulinum toxin type A (BoNT-A) injection patterns customized to each patient's unique tremor characteristics produce better efficacy and lower adverse effects compared to the fixed-muscle-fixed-dose approach for Essential Tremor (ET) and Parkinson's disease (PD) tremor therapy. This article outlined how a kinematic-based dosing method to standardize and customize BoNT-A injections for tremors was developed. Seven ET and eight PD participants with significant tremor reduction and minimal perceived weakness using optimized BoNT-A injections determined by clinical and kinematic guidance were retrospectively selected to develop the kinematic-based dosing method. BoNT-A dosages allocated per joint were paired to baseline tremor amplitudes per joint. The final kinematic-based dosing method was prospectively utilized to validate BoNT-A injection pattern selection without clinical/visual assessments in 31 ET and 47 PD participants with debilitating arm tremors (totaling 122 unique tremor patterns). Whole-arm kinematic tremor analysis was performed at baseline and 6-weeks post-injection. Correlation and linear regression analyses between baseline tremor amplitudes and the change in tremor amplitude 6-weeks post-injection, with BoNT-A dosages per joint, were performed. Injection patterns determined using clinical assessment and interpretation of kinematics produced significant associations between baseline tremor amplitudes and optimized BoNT-A dosages in all joints. The change in elbow tremor was only significantly associated with the elbow total dose as the change in the wrist and shoulder tremor amplitudes were not significantly associated with the wrist and shoulder dosages from the selected 15 ET and PD participants. Using the kinematic-based dosing method, significant associations between baseline tremor amplitudes and the change (6-weeks post-first treatment) in tremor at each joint with BoNT-A dosages for all joints was observed in all 78 ET and PD participants. The kinematic-based dosing method provided consistency in dose selection and subsequent tremor reduction and can be used to standardize tremor assessments for whole-arm tremor treatment planning.

Ultrasound (US)-guided botulinum neurotoxin (BoNT) injections are becoming a mainstay in the treatment of muscle spasticity in upper motor neuron syndromes. As a result, there has been a commensurate increase in US-guided BoNT injection for spasticity training courses. However, many of these courses do not emphasize the importance of ergonomics. This paper aims to highlight the importance of ultrasound ergonomics and presents ergonomic recommendations to optimize US-guided BoNT injection techniques in spasticity management. Expert consensus opinion of 11 physicians (4 different continents; representing 8 countries, with an average of 12.6 years of practice using US guidance for BoNT chemodenervation (range 3 to 22 years)). A search using PubMed, College of Physicians and Surgeons of British Columbia database, EMbase was conducted and found no publications relating the importance of ergonomics in US-guided chemodenervation. Therefore, recommendations and consensus discussions were generated from the distribution of a 20-question survey to a panel of 11 ultrasound experts. All 11 surveyed physicians considered ergonomics to be important in reducing physician injury. There was complete agreement that physician positioning was important; 91% agreement that patient positioning was important; and 82% that ultrasound machine positioning was important. Factors that did not reach our 80% threshold for consensus were further discussed. Four categories were identified as being important when implementing ultrasound ergonomics for BoNT chemodenervation for spasticity; workstation, physician, patient and visual ergonomics. Optimizing ergonomics is paramount when performing US-guided BoNT chemodenervation for spasticity management. This includes proper preparation of the workspace and allowing for sufficient pre-injection time to optimally position both the patient and the physician. Lack of awareness of ergonomics for US-guided BoNT chemodenervation for spasticity may lead to suboptimal patient outcomes, increase work-related injuries, and patient discomfort. We propose key elements for optimal positioning of physicians and patients, as well as the optimal setup of the workspace and provide clinical pearls in visual identification of spastic muscles for chemodenervation.

Background: Recent cell-based and animal experiments have demonstrated an effective reduction in botulinum neurotoxin A (BoNT/A) by copper., Aim: We aimed to analyze whether the successful symptomatic BoNT/A treatment of patients with Wilson's disease (WD) corresponds with unusually high doses per session., Methods: Among the 156 WD patients regularly seen at the outpatient department of the university hospital in Düsseldorf (Germany), only 6 patients had been treated with BoNT/A during the past 5 years. The laboratory findings, indications for BoNT treatment, preparations, and doses per session were extracted retrospectively from the charts. These parameters were compared with those of 13 other patients described in the literature., Results: BoNT/A injection therapy is a rare (<4%) symptomatic treatment in WD, only necessary in exceptional cases, and is often applied only transiently. In those cases for which dose information was available, the dose per session and indication appear to be within usual limits., Conclusion: Despite the evidence that copper can interfere with the botulinum toxin in preclinical models, patients with WD do not require higher doses of the toxin than other patients with dystonia.

This study aimed to determine the long-term quality of life (QoL) in hemifacial spasm (HFS) patients after treating with Abo-botulinum toxin A (Abo-BTX). The study assessed the disease-specific QoL (hemifacial spasm questionnaire 30 items; HFS 30), the involuntary movements (abnormal involuntary movement scale; AIMS), general health QoL (Medical Outcomes 36-Item Short Form Health Survey; SF-36), and Depression (the Center of Epidemiologic Studies-Depression questionnaire; CES-D). A total of 74 HFS patients were enrolled from 2012 to 2017. The disease-specific QoL; involuntary movements; and the general health domain of SF 36 were significantly improved after injections of Abo-BTX A in the first few years ( p < 0.04), but significantly decreased at the fifth year of treatment without significant clinical resistance observed ( p < 0.001). Only the general health domain of SF 36 showed persistent improvement over five years ( p = 0.02). In summary, Abo-BTX A can improved quality of life in the first few years; however only the general health domain of SF-36 showed significant improvement over five years ( p = 0.02). No clinical resistance was observed.

AbobotulinumtoxinA (aboBoNT-A) has been used for various cosmetic purposes, including minimization of moderate to severe lines, or other cosmetic indications, in the face and neck. We carried out a systematic review to identify all relevant evidence on the treatment approaches and outcomes of aboBoNT-A as a cosmetic treatment of the middle and lower areas of the face, and the neck. Embase, MEDLINE, Cochrane Library, congress proceedings and review bibliographies were searched for relevant studies. Identified articles were screened against pre-specified eligibility criteria. Of 560 unique articles identified, 10 were included for data extraction (three observational studies, 1 randomized controlled trial [with two articles] and five non-randomized trials). The articles provided data on gummy/asymmetric smile (2), marionette lines (5), masseter muscle volume (2), nasal wrinkles (2), perioral wrinkles (3) and the platysma muscle (4). All articles reporting on efficacy of aboBoNT-A demonstrated positive results, including reduction of wrinkles (5), reduction of masseter muscle (2) and degree of gummy smile (1) compared with before treatment. No serious adverse events were reported and patient satisfaction was high. In conclusion, positive findings support further research of aboBoNT-A for the middle and lower areas of the face, and in the neck, which are largely unapproved indications.

Unilateral peripheral facial nerve palsy jeopardizes quality of life, rendering psychological consequences such as low self-esteem, social isolation, anxiety, and depression. Among therapeutical approaches, use of Botulinum toxin type A (BoNT-A) on the nonparalyzed side has shown promising results and improvement of quality of life. Nevertheless, the correct technique is paramount, since over-injection of the muscles can result in lack of function, leading to a "paralyzed" appearance, and even worse, functional incompetence, which may cause greater distress to patients. Therefore, the objective of this article is to provide a practical guideline for botulinum toxin use in facial palsy. To this aim, adequate patient assessment, BoNT-A choice, injection plan and dosage, and injection techniques are covered.

Opisthotonus refers to abnormal axial extension and arching of the trunk produced by excessive contractions of the paraspinal muscles. In childhood, the abnormal posture is most often related to dystonia in the setting of hypoxic injury or a number of other acquired and genetic etiologies. The condition is often painful, interferes with ambulation and quality of life, and is challenging to treat. Therapeutic options include oral benzodiazepines, oral and intrathecal baclofen, botulinum neurotoxin injections, and deep brain stimulation. Management of opisthotonus within the pediatric population has not been systematically reviewed. Here, we describe a series of seven children who presented to our institution with opisthotonus in whom symptom relief was achieved following administration of botulinum neurotoxin injections.

The mentalis muscle is now considered key structures when performing procedures for rejuvenating the lower face. The aim of this study was to determine the anatomical morphology and location of the mentalis muscle and thereby provide anatomical information for facilitating clinical procedures designed to rejuvenate the lower face. Forty-four adult hemifaces from five Thai cadavers and 21 Korean cadavers were dissected to identify the locations of the mentalis muscle. Sixty-six hemifaces from 33 healthy young Korean subjects were included in an ultrasonographic study. The depth of the mentalis muscle below the skin surface, the thickness of the mentalis muscle, and the distance from the bone to the mentalis muscle were measured at the two points that were 5 mm lateral to the most-prominent point of the chin. The mentalis muscle was classified into two types based to its shape: in type A (86.4%, 38 of the 44 cases) it was dome shaped in three dimensions, while in type B (13.6%, 6 of the 44 cases) it was flat. The mentalis muscle was present mostly at the area 5-10 mm from the midsagittal line and 20-30 mm from a horizontal line connecting the mouth corners. The mentalis muscle was present between depths of 6.7 to 10.7 mm below the skin. This new information about the location of the mentalis muscle may help when identifying the most effective and safe botulinum toxin injection points and depths during esthetic procedures for weakened facial rhytides on the lower face.

The purpose of this study was to determine and compare the effects between injecting botulinum toxin A (BTX-A) transconjunctivally into the palpebral lobe and transcutaneously into the orbital lobe of the lacrimal gland in patients with epiphora due to lacrimal outflow obstruction. This randomized controlled study included 53 eyes of 31 patients with unilateral or bilateral epiphora. Patients were randomly allocated to receive an injection of BTX-A (3 units) either transconjunctivally ( n = 15, 25 eyes) or transcutaneously ( n = 16, 28 eyes). For objective assessments, the tear meniscus height and Schirmer's I test with topical anesthesia were measured at baseline and after 2, 6, 12, and 24 weeks of follow-up. Subjective evaluations were performed using the Munk score. After BTX-A injection, patients in both groups experienced significant objective and subjective reductions in tearing at all follow-up times compared to pre-injection (success rate 86.8%), and the effect lasted for a mean duration of 5.63 months. The two delivery routes showed similar clinical effectiveness for a single injected dose of BTX-A. In conclusion, injecting BTX-A via either a transconjunctival or transcutaneous route helps to reduce normal tear production and results in significant improvements in the symptoms in patients with epiphora.

A novel technique for the diagnosis and management of middle ear myoclonus is described. A patient with middle ear myoclonus underwent a trans-canal microscopic middle ear exploration with injection of botulinum toxin into the stapedius and tensor tympani muscles. Postoperatively, the patient noted complete resolution of symptoms. This is the first report of the use of botulinum toxin directly applied to the middle ear musculature via a trans-canal approach for the management of middle ear myoclonus. This approach is both a useful diagnostic and therapeutic tool that allows for temporary muscle paralysis prior to offering definitive surgical management. Laryngoscope, 131:E248-E249, 2021., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Three patients ranging from 49 to 61 years-old presented to our pain clinic after failing multiple treatment attempts for debilitating, chronic post-traumatic headaches, neck pain and involuntary muscle spasm following gunshot wounds to the head, neck and face. Concurrent cervical dystonia was noted in each patient on presentation. All patients were treated with onabotulinumtoxin A (ONA) injections in the head and neck. Each patient reported between 70% and 100% improvement of their headache pain, neck pain and spasm with a significant reduction in the frequency, duration and intensity of their headaches. This level of improvement has been successfully maintained in all three patients with regular ONA injections at 90-day intervals. Two patients experienced a single relapse in symptoms when scheduling conflicts caused them to miss their regularly scheduled ONA injections by several weeks. These symptoms resolved when their ONA injections resumed, suggesting that ONA is the causative agent alleviating their symptoms., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Botulinum toxin type A (BoNTA) is a powerful neurotoxin that inhibits acetylcholine release from presynaptic vesicles. The potency and safety profile of BoNTA grant the toxin vast therapeutic potential. It has been used off-label for a variety of dermatologic conditions. This review aims to analyze published literature regarding the benefits and risks of the off-label use of BoNTA beyond facial lines, including eccrine hidrocystomas, enlarged pores, keloids and hypertrophic scars, hidradenitis suppurativa, hyperhidrosis, masseter muscle hypertrophy, and salivary gland hypertrophy, among others. A MEDLINE search from January 2000 to December 2019 was conducted on the off-label uses of botulinum toxin in dermatology.

Background: Microbotulinum refers to the systematic injection of tiny blebs of diluted botulinum toxin at repeated intervals into the skin. This targets the superficial fibers of the facial muscles, and weakens their insertion into the undersurface of the skin, which is responsible for the fine lines and wrinkles on the face. The authors present a pilot study based on quantitative evaluation, by means of a skin-scanning technology, of the aesthetic improvement of skin texture, microroughness, and enlarged pore size in a patient group treated with microbotulinum injections for cosmetic purposes., Methods: The treatment was performed using a 32-gauge needle to deliver injections on a regular 1-cm grid from the forehead to the cheek and down to the jawline., Results: Sixty of the 62 patients completed the study. All analyzed parameters improved significantly (p < 0.0001) at 90 days with respect to the pretreatment time point (skin texture, -1.93 ± 0.51; microroughness, -2.48 ± 0.79; and pore diameter, 2.1 ± 0.43). Best results have been obtained in patients aged between 42.7 and 46.8 years, and standard deviation calculation allows us to recommend it in patients aged between 36.5 and 53 years., Conclusions: The results of this pilot study suggest that intradermal botulinum toxin injection, or so-called microbotulinum, is a safe and effective method to treat skin flaws. Because of the high satisfaction rate among both physicians and patients, further studies are indeed mandatory to determine the optimal number of units needed for a longer and lasting effect with this particular novel dilution., Clinical Question/level of Evidence: Therapeutic, IV.

Background: Acute cerebrovascular accident poses a threat to the health of the nation. Dynamic electric neurostimulation decreases the excitability of the receptor apparatus, optimize microcirculatory processes, analgesic and antispasmodic effects., Methods: This article discusses the rehabilitation of 96 men and women with post-stroke spasticity, mean age of 60.51 ± 4.9 years, in the early recovery period after ischemic stroke, randomized into 4 equal groups: Group 1 received botulinum toxin therapy in combination with dynamic electric neurostimulation and basic therapy, including massage and therapeutic exercises; Group 2 -botulinum toxin therapy and basic therapy; Group 3 - dynamic electric neurostimulation and basic therapy; Group 4 - basic therapy only. Study methods included the use of the Modified Asworth Scale to assess spasticity, the Rivemead Motor Assessment test, and goniometry to assess the range of joint movements., Results: During a three-week observation, it was found that the inclusion of botulinum toxin therapy and dynamic electrical neurostimulation in the standard therapy of post-stroke spasticity in patients after ischemic stroke in the early recovery period contributed to patients' recovery., Conclusions: Botulinum toxin therapy and dynamic electrical neurostimulation contributed to a more significant decrease in spasticity in the proximal and distal parts of the paretic upper extremity. It is also increased the amplitude of voluntary movements in the affected shoulder, elbow, and wrist joints, compared to the separate use of botulinum toxin therapy and dynamic electric neurostimulation as part of basic rehabilitation., Competing Interests: Declaration of Competing Interest None, (Copyright © 2020 Elsevier Inc. All rights reserved.)

Chronic stroke survivors with spastic hemiplegia have various clinical presentations of ankle and foot muscle spasticity patterns. They are mechanical consequences of interactions between spasticity and weakness of surrounding muscles during walking. Four common ankle and foot spasticity patterns are described and discussed through sample cases. The patterns discussed are equinus, varus, equinovarus, and striatal toe deformities. Spasticity of the primary muscle(s) for each deformity is identified. However, it is emphasized that clinical presentation depends on the severity of spasticity and weakness of these muscles and their interactions. Careful and thorough clinical assessment of the ankle and foot deformities is needed to determine the primary cause of each deformity. An understanding of common ankle and foot spasticity patterns can help guide clinical assessment and selection of target spastic muscles for botulinum toxin injection or nerve block.

Chemodenervation of cervical musculature using botulinum neurotoxin (BoNT) is established as the gold standard or treatment of choice for management of Cervical Dystonia (CD). The success of BoNT procedures is measured by improved symptomology while minimizing side effects and is dependent upon many factors including: clinical pattern recognition, identifying contributory muscles, BoNT dosage, and locating and safely injecting target muscles. In patients with CD, treatment of anterocollis (forward flexion of the neck) and anterocaput (anterocapitis) (forward flexion of the head) are inarguably challenging. The longus Colli (LoCol) and longus capitis (LoCap) muscles, two deep cervical spine and head flexor muscles, frequently contribute to these patterns. Localizing and safely injecting these muscles is particularly challenging owing to their deep location and the complex regional anatomy which includes critical neurovascular and other structures. Ultrasound (US) guidance provides direct visualization of the LoCol, LoCap, other cervical muscles and adjacent structures reducing the risks and side effects while improving the clinical outcome of BoNT for these conditions. The addition of electromyography (EMG) provides confirmation of muscle activity within the target muscle. Within this manuscript, we present a technical description of a novel US guided approach (combined with EMG) for BoNT injection into the LoCol and LoCap muscles for the management of anterocollis and anterocaput in patients with CD.

To study the jitter parameters in the distant (DM) and the adjacent muscle (AM) after botulinum neurotoxin type A (BoNT/A) injection in 78 patients, jitter was measured by voluntary activation in DM ( n = 43), and in AM ( n = 35). Patients were receiving BoNT/A injections as a treatment for movement disorders. Mean age 65.1 years (DM) and 61.9 years (AM). The mean jitter was abnormal in 13.9% (maximum 41.4 µs) of DM, and 40% (maximum 43.7 µs) of AM. Impulse blocking was sparse. We found no correlation of the mean jitter to age, BoNT/A most recent injection (days/units), number of muscles injected, total BoNT/A units summated, number of total BoNT/A sessions, beta-blockers/calcium channel blockers use, and cases with local spread symptoms such as eyelid drop/difficulty swallowing. Maximum mean jitter (41.4/43.7 µs) for DM/AM occurred 61 and 131 days since the most recent BoNT/A, respectively. The far abnormal mean jitter (32.6/36.9 µs) occurred 229 and 313 days since the most recent BoNT/A. We suggested that jitter measurement can be done after BoNT/A in a given muscle other than the injected one, after 8 (DM) and 11 (AM) months, with reference >33 µs and >37 µs, respectively.

This study aimed to evaluate and compare the efficacy and safety of mid-urethral sling (MUS) with botulinum toxin A (BoNT-A) versus MUS only in women with mixed urinary incontinence. This was a comparative observational study, and total of 73 patients were enrolled. A total of 38 and 35 patients received MUS only and MUS with BoNT-A injection, respectively. The efficacy outcome included change in Urinary Incontinence Outcome Scores (UIOS), change in Overactive Bladder Symptom Score (OABSS), and use of antimuscarinic agent or beta-3 agonist. Safety assessments included adverse events including urinary retention, increased postvoid residual volumes, and urinary tract infection. MUS with BoNT-A injection was insignificantly better than MUS only in urinary incontinence outcome (88% vs. 71%, respectively, p = 0.085) at week three. Among the 33 patients with detrusor overactivity (DO), patients who received BoNT-A had a higher cure rate of incontinence (88% vs. 41%, p = 0.01) and less required antimuscarinic agent or beta-3 agonist (31% vs. 94%, p < 0.001) compared to patients who did not receive BoNT-A injection. There was no significant difference in the incidences of adverse events between two groups. BoNT-A injection with MUS demonstrated efficacy and safety in the treatment of mixed urinary incontinence, specifically for women with DO.

Purpose Ocular motility disturbances following retinal detachment surgery are well documented, resulting in ocular misalignment and disabling diplopia. Interestingly, there has been a downward trend over the last decade across the United Kingdom with the evolution of refined vitrectomy techniques and instrumentation. We aim to report our updated experience on factors influencing botulinum toxin outcomes in view of the trend toward vitrectomy. Methods The Moorfields strabismus service carried out a follow-up retrospective study of all subjects that received botulinum toxin for retinal surgery-related strabismus at our center over an eleven-year period. All new onset constant or intermittent strabismus following retinal detachment surgery were included. Botulinum toxin response was stratified to good and poor. Results 32 patients fulfilled our criteria, with a mean follow-up of 20 months. The majority were vitrectomised eyes (62%), presented with diplopia (60%) and exotropia (66%). All isolated and combined vertical deviations (18%) were noted among cryobuckled eyes only. Baseline largest mean horizontal deviation was 49 and 51 prism diopters (PD) among the good and poor responders, respectively. A statistically and clinically significant reduction in the horizontal angle of deviation was noted among the good ( p < .0001) responders, requiring a mean of six injections, in comparison to the poor responders ( p = .03). Of the good responders, five patients (16%) with decompensated phorias regained fusion control. A small number of complications (15%) were noted, the most marked being intractable diplopia in a good responder (3%) with failure to fuse. Conclusions Botulinum toxin is a useful treatment modality, particularly when surgical options are limited. It can restore binocularity in patients with preexisting fusion potential. Ocular cosmesis can be achieved but requires ongoing injections. Barriers to fusion restoration include multiple retinal surgeries, persistent macula pathology and central-peripheral retinal rivalry. This highlights the need for rigorous baseline macula assessment to allow a tailored approach when considering botulinum toxin therapy for strabismus.

Spasticity is a common disabling disorder in adult subjects suffering from stroke, brain injury, multiple sclerosis (MS) and spinal cord injury (SCI). Spasticity may be a disabling symptom in people during rehabilitation and botulinum toxin type A (BTX-A) has become the first-line therapy for the local form. High BTX-A doses are often used in clinical practice. Advantages and limitations are debated and the evidence is unclear. Therefore, we analysed the efficacy, safety and evidence for BTX-A high doses. Studies published from January 1989 to February 2020 were retrieved from MEDLINE/PubMed, Embase, Cochrane Central Register. Only obabotulinumtoxinA (obaBTX-A), onabotulinumtoxinA (onaBTX-A), and incobotulinumtoxinA (incoBTX-A) were considered. The term "high dosage" indicated ≥ 600 U. Thirteen studies met the inclusion criteria. Studies had variable method designs, sample sizes and aims, with only two randomised controlled trials. IncoBTX-A and onaBTX-A were injected in three and eight studies, respectively. BTX-A high doses were used predominantly in treating post-stroke spasticity. No studies were retrieved regarding treating spasticity in MS and SCI. Dosage of BTX-A up to 840 U resulted efficacious and safety without no serious adverse events (AEs). Evidence is insufficient to recommend high BTX-A use in clinical practice, but in selected patients, the benefits of high dose BTX-A may be clinically acceptable., Competing Interests: The authors declare no conflict of interest.

This study describes the nerve entry point and intramuscular nerve branching of the rhomboid major and minor, providing essential information for improved performance of botulinum toxin injections and electromyography. A modified Sihler method was performed on the rhomboid major and minor muscles (10 specimens each). The nerve entry point and intramuscular arborization areas were identified in terms of the spinous processes and medial and lateral angles of the scapula. The nerve entry point for both the rhomboid major and minor was found in the middle muscular area between levels C7 and T1. The intramuscular neural distribution for the rhomboid minor had the largest arborization patterns in the medial and lateral sections between levels C7 and T1. The rhomboid major muscle had the largest arborization area in the middle section between levels T1 and T5. In conclusion, botulinum neurotoxin injection and electromyography should be administered in the medial and lateral sections of C7-T1 for the rhomboid minor and the middle section of T1-T7 for the rhomboid major. Injections in the middle section of C7-T1 should also be avoided to prevent mechanical injury to the nerve trunk. Clinicians can administer safe and effective treatments with botulinum toxin injections and other types of injections by following the methods in our study.

Introduction: Scrotal rejuvenation is a real male aesthetic demand. Scrotal injection of botulinum toxin makes the testicles smoother, less dangling and subjectively larger., Methods: Intrascrotal botulinum toxin injections were performed to a 44-year-old patient for aesthetic purposes. We used the intracremasteric injection protocol. Cremaster muscle injections and dartos muscle injections were performed., Results: The patient was satisfied. No adverse reaction to the intrascrotal botulinum toxin injection was observed. The patient wanted to repeat the procedure in the future., Conclusion: At the moment, there is no recommendation about the aesthetic use of intrascrotal injections of botulinum toxin A and the risks are unknown. The purpose of this article is to show the feasibility, context and technical modalities of intrascrotal injection. The risk of infertility is real, but marginal for men who no longer have progeny's desire., Level of Evidence: Level 3., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background: Botulinum toxin type A injection is a common aesthetic treatment that can be used alone or in combination to rejuvenate the entire face and neck., Objectives: To assess the safety and efficacy of a full-face approach with botulinum toxin type A., Methods: This was a single-center, retrospective review of data from 189 patients receiving full-face and neck treatment with onabotulinumtoxinA in the following areas: glabellar lines, crow's feet lines, forehead lines, bunny lines, sagging nasal tip, gummy smile, marionette lines, mentalis, masseter, and lateral/anterior platysma., Results: The mean age was 56.6 ± 9.2 years, and 94.7% were women (n = 179). Patients received a total of 394 full-face treatments (mean: 2.1 per person; range 1-7). The mean quantity of onabotulinumtoxinA injected was 113.8 ± 17.6 units per treatment (range: 50-180 units). The most frequently injected areas were the glabella/crow's feet/forehead (n = 383; 97.2%), platysma (n = 378; 95.9%), bunny lines (n = 283; 71.8%), and chin (n = 120; 30.5%). Six patients (3.2%) experienced complications: five cases of unwanted diffusion from the mentalis into the depressor labii inferioris and one case of right eyelid ptosis after injection in the upper third. All were minor and none appeared to be related to overall dose., Conclusions: Full-face and neck treatment with onabotulinumtoxinA can be performed without substantial safety concerns, often leading to excellent results. This approach may become increasingly prevalent in the coming years., (© 2019 Wiley Periodicals, Inc.)

Background: Full-face aesthetic treatment involving several treatment modalities may improve facial aesthetic outcome., Objective: To evaluate clinical outcomes and patient perceptions of monotherapy with either abobotulinumtoxinA (ABO) or hyaluronic acid (HA) filler followed by full-face combination treatments of ABO, HA filler, and skin-boosting HA (RSB)., Materials and Methods: Subjects aged 35 to 50 years were randomized to monotherapy with 50 s.U ABO in the glabella or ≤1 mL HA filler in the nasolabial folds (NLFs)/cheeks. At Month 6 and Month 12, all subjects received combination treatment with ≤50 s.U ABO in the glabella, ≤2 mL HA filler in the NLFs/cheeks (and other facial areas as applicable), and ≤1 mL RSB (additional RSB treatment at Month 7). Assessments included global facial aesthetic appearance and improvement, first impression, perceived age, wrinkle severity, satisfaction questionnaires, and adverse events., Results: Repeated full-face combination treatment with ABO, HA filler, and RSB was associated with considerably higher levels of aesthetic improvement and subject satisfaction than monotherapy with ABO or HA filler. Improvement rate of glabellar lines was increasing with each treatment., Conclusion: Repeated combination treatment achieved greater change in global facial aesthetic appearance than monotherapy. Aesthetic improvement and subject satisfaction was high and increased with each treatment. All treatments were well tolerated.

Aims: To examine changes in objective and subjective drooling severity measures after submandibular botulinum neurotoxin A injection in children with neurodevelopmental disabilities, explore their relationship, and evaluate if clinically relevant responses relate to changes in the impact of drooling., Method: This longitudinal, observational cohort study involved 160 children (92 males, 68 females; 3-17y, mean 9y 1mo, SD 3y 6mo) treated between 2000 and 2012 at the Radboud University Medical Center, Nijmegen, the Netherlands. Repeated measures analysis of variance was used to compare the 5-minute Drooling Quotient (DQ5) and Visual Analogue Scale (VAS) for drooling severity pretreatment and posttreatment, and Pearson's rho to assess their association. A parent questionnaire was used to assess drooling impact in responders (defined as ≥50% reduction in DQ5 and/or ≥2 SD reduction in VAS for drooling severity 8wks postintervention) and non-responders., Results: One hundred and twelve children (70%) were responders. Their mean VAS for drooling severity and DQ5 scores were significantly lower 32 weeks postintervention compared to baseline. At baseline, the VAS for drooling severity-DQ5 relationship was 'weak' (r s =0.15, p=0.060), whereas it was 'fair' at 8 weeks (r s =0.43, p=0.000) and 32 weeks (r s =0.30, p=0.000). For responders, a significant change was found regarding the impact of drooling on daily care and social interactions at 8 weeks after intervention; most of these effects were maintained at 32 weeks., Interpretation: A clinically relevant response based on a combination of objective and subjective measures of drooling severity was accompanied by positive changes regarding the impact of drooling on daily care and social interactions., What This Paper Adds: Botulinum neurotoxin A injection into the submandibular glands reduced drooling severity in 70% of children with neurodevelopmental disabilities. Objective (5-minute Drooling Quotient) and subjective (Visual Analogue Scale for drooling severity) measures correlated 8 and 32 weeks after treatment. Objective and subjective measures complemented each other when changes in drooling severity were assessed. Reduced drooling severity was accompanied by positive changes with regard to the impact of drooling., (© 2019 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)

Introduction: In patients with neurogenic bladder outlet incompetence, a bladder outlet procedure (BOP) may be required to achieve urinary continence. However, when performed in isolation, a BOP can be associated with bladder deterioration and upper-tract injury. In the event of bladder deterioration, additional procedures such as bladder augmentation (BA) or botulinum toxin injection (BTI) may be pursued., Objective: The aim of this study was to assess long-term outcomes after isolated BOP in a pediatric myelomeningocele (MMC) population, including the need for additional surgical intervention in the form of BTI or BA., Materials and Methods: A retrospective cohort study was performed for patients with MMC who underwent an isolated BOP between 2004 and 2017. Primary outcomes included the need for postoperative BTI or BA. Secondary outcomes included the association between preoperative urodynamic parameters and need for BTI or BA., Results: BTI or BA was performed in 18 of 36 (50%) patients at a median of 17.8 months (IQR 11.2-29.3) after an isolated BOP. A median of 1 (IQR 1-3) BTI was performed in 11 (30.6%) patients. BA was performed in 9 (25%) patients, including 2 patients who previously underwent BTI. Patients who did not undergo BTI or BA after BOP had a slightly increased percentage estimated bladder capacity at the end of follow-up (107% versus 95%, p=0.42). By contrast, patients who underwent BTI or BA had a post-BOP percentage estimated bladder capacity that decreased from 112 to 70% (p < 0.001), increased maximum detrusor leak point pressure from 43 to 67 cm H 2 O (p = 0.01), and higher rate of de novo upper-tract changes. Unfortunately, no preoperative clinical, radiographic, or urodynamic factors predicted the need for BTI or BA., Discussion: On time-to-event analysis, the risk of BTI or BA was 53% at 5 years in our cohort. Risk of these procedures was highest in the first two years after BOP. 9 of 11 (82%) patients who underwent BTI had improvement in bladder dynamics and BA was not pursued. These findings suggest that BTI provides a less-morbid alternative to BA in patients with MMC and de novo adverse bladder storage changes after an isolated BOP., Conclusion: The need for BTI or BA after an isolated BOP is significant in patients with MMC. BTI offers a less-invasive alternative to BA in this population., (Copyright © 2019 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Introduction : Botulinum toxin (BoNT) is a protein secreted by the anaerobic Gram-negative bacterium Clostridium botulinum . Among the seven known subtypes, type A is the most commonly used in women to treat diseases. It primarily blocks presynaptic release of acetylcholine at the neuromuscular junction, resulting in temporary muscle paralysis; thus, it is suitable for treating dystonia and other systemic diseases. BoNT is used widely for treating diseases that persist throughout, and may worsen during, pregnancy, such as cervical dystonia and achalasia. Thus, it is important to investigate whether BoNT injection during pregnancy causes side effects in pregnant women, fetuses, or newborns. Areas covered : This review highlights the efficiency and safety of BoNT injection in pregnancy. and assessed current literature with respect to the use of BoNT for disease treatment during pregnancy. Expert opinion : BoNT injection does not increase the risk of complications in pregnant women and fetuses. However, the use of BoNT to treat disease during pregnancy requires fully informed consent from patients. In addition, further research is needed to determine how to reduce the side effects of BoNT injection during pregnancy (e.g., by improving drug composition, or adjusting the amount of BoNT or the injection interval).

Background: Endoscopic intrasphincteric injection of Botox (ISIB) is used routinely for the treatment of achalasia esophagus and other spastic motor disorders. Studies show that the ISIB reduces the smooth muscle lower esophageal sphincter (LES) pressure. The esophageal hiatus, formed by the right crus of diaphragm, surrounds the cranial half of the LES and works like an external LES. We studied the effects of ISIB on the LES and hiatal contraction and gastroesophageal reflux (GER). Fourteen patients treated with ISIB were studied. Esophageal manometry-impedance recordings were performed before and after the ISIB. Hiatal contraction was assessed during tidal inspiration, forced inspiration, Müller's maneuver, and straight leg raise. In 6 subjects, the manometry were repeated 6-12 mo after the ISIB. The esophagogastric junction (EGJ) pressure was measured at end expiration (LES pressure) and at the peak of maneuvers (hiatal contraction). Transdiaphragmatic pressure (pdi; force of diaphragmatic contraction) was measured at the peak of forced inspiration. GER was measured from the impedance recordings. The EGJ pressure at end expiration (LES pressure) decreased significantly after the Botox injection. The peak EGJ pressure at tidal inspiration, forced inspiration, Müller's maneuver, and straight leg raise was also dramatically reduced by the ISIB. There was no effect of Botox on the pdi during forced inspiration. Seven of 10 subjects demonstrated GER during maneuvers following the ISIB. Six to 12 mo after ISIB, the LES and hiatal contraction pressure returned to the pre-ISIB levels. ISIB, in addition to decreasing LES pressure, paralyzes the esophageal hiatus (crural diaphragm) and induces GER. NEW & NOTEWORTHY The sphincter mechanism at the lower end of the esophagus comprises smooth muscle lower esophageal sphincter (LES) and skeletal muscle crural diaphragm (hiatus). Current thinking is that the endoscopic intrasphincteric injection of Botox (ISIB), used routinely for the treatment of achalasia esophagus, reduces LES pressure. Our study shows that ISIB, even though injected into the LES, diffuses into the hiatus and causes its paralysis. These findings emphasize the importance of esophageal hiatus as an important component of the antireflux barrier and that the ISIB is refluxogenic.

Aim: This study evaluated whether the effect of submandibular gland botulinum neurotoxin A (BoNT-A) injection can predict the outcome of submandibular duct relocation with sublingual gland excision (SMDR) in children with drooling. Furthermore, we compared the effectiveness of both procedures., Method: A retrospective cohort study was performed in 42 children and adolescents (25 males, 17 females; mean [SD] age at BoNT-A injection 11y [4], range 4-20y; mean [SD] age at SMDR 15y [4], range 7-23y) with cerebral palsy or another non-progressive developmental disability who had undergone both BoNT-A injection and SMDR for drooling. Main outcomes were the drooling quotient and the visual analogue scale (VAS) on drooling severity at 8 weeks and 32 weeks follow-up., Results: Failure or success of previous BoNT-A injections had no influence on success of consecutive SMDR. Relative change in main outcomes showed no significant relation between BoNT-A injection and SMDR for any follow-up measurement. After 8 weeks, SMDR was more successful than BoNT-A injection in diminishing VAS (VAS 80.0% vs 54.3%; drooling quotient 56.2% vs 51.0%). After 32 weeks, both drooling quotient (64.3% vs 29.5%) and VAS (75.7% vs 37.1%) showed significantly higher proportions of success for SMDR., Interpretation: The effect of submandibular BoNT-A injection does not predict subsequent SMDR success in drooling. Furthermore, SMDR has a larger and longer-lasting positive effect on drooling than BoNT-A injections., What This Paper Adds: Submandibular botulinum neurotoxin A (BoNT-A) injection effect does not predict submandibular duct relocation with sublingual gland excision outcome. Submandibular duct relocation is more effective and more permanent than BoNT-A injection., (© 2019 Mac Keith Press.)

Background: Two licensed reconstitution volumes may be used to achieve the recommended abobotulinumtoxinA (ABO) dose for glabellar line correction., Objective: Comparison of efficacy, safety, and subject satisfaction concerning treatment of moderate to severe glabellar lines with 2 different ABO reconstitution volumes., Materials and Methods: Phase IV, prospective, randomized, multicenter, subject- and evaluator-blinded study: 60 subjects received 1 ABO (50 units) treatment, administered as a 1.5- or 2.5-mL reconstitution. Primary objective was Day 30 improvements (≥1-point) in glabellar line severity. Onset of effect, duration, subject satisfaction, and treatment-related adverse events (AEs) were assessed., Results: At Day 30, 90.0% and 86.7% of subjects achieved ≥1-point improvements with 1.5- and 2.5-mL reconstitutions, respectively. Median time to onset of effect was 48 hours after treatment. At 24 hours, 26.7% achieved ≥1-point improvements with the 2.5-mL reconstitution versus 6.7% with the 1.5-mL reconstitution. Maximum response was at Day 14, and >40% maintained efficacy through Day 120 in each group. High subject satisfaction was sustained throughout observation. Most AEs were mild. No serious AEs were reported., Conclusion: Both ABO reconstitutions were well tolerated and effective in correcting glabellar lines with no significant differences concerning efficacy or duration of effect. No serious AEs were reported.

Based on epidemiological data it was believed that botulinumtoxin type D (BT-D) may not block human cholinergic synapses. We wanted to investigate BT-D's effect on the autonomic cholinergic synapse in humans. For this, we compared in four volunteers intraindividually the hypohidrotic effect of intradermal BT-D and BT-A in Minor's iodine starch sweat test. Altogether, we studied BT-D in doses of 4, 8, 16 and 32MU and BT-A in doses of 2, 4, 8 and 16MU at weekly intervals throughout a period of 13 weeks. All BT doses were diluted in 0.2 ml 0.9% NaCl/H 2 O. Overall 704 data points were collected. Combined over all four subjects and all four doses BT-D's hypohidrotic effect intensity was half of BT-A's. BT-D's effect peaked around 5 weeks, BT-A's around 7 weeks. BT-D's effect duration was around 12 weeks, of BT-A's was around 14 weeks. For both BT types the hypohidrotic effect was dose dependent. BT-D, when injected intradermally, can block autonomic cholinergic synapses in humans. Compared to BT-A, BT-D's effect intensity was half and its effect duration was some 2 weeks shorter. With its weaker and shorter effect BT-D does not seem to promise therapeutic effects superior to BT-A.

The objective of this study is to discover whether incobotulinumtoxinA (inco) can reduce relative hypersalivation in patients with amyotrophic lateral sclerosis (ALS). 14 patients with ALS (8 males and 6 females, age 55.4 ± 16.3 years) received ultrasound-guided injection of inco 100 MU in both parotid glands and inco 50 MU in both submandibular glands. Saliva production was gravimetrically measured with three cotton rolls placed in the mouth. Weight increase after 5 min was measured on an electronic scale. Subjective saliva production was registered with drooling frequency scale (DFS) and drooling severity scale (DSS). Saliva production was gravimetrically reduced at week 4 (p = 0.04), week 8 (p = 0.01) but not after week 12 after BT application. DFS was reduced at week 4 (p = 0.04), week 8 (p = 0.02), but not after week 12. DSS was reduced at week 4 (p = 0.03), week 8 (p = 0.04) and week 12 (p = 0.04). Patients in our study did not experience changes in their swallowing patterns or any other safety-relevant events. Inco is effective and well tolerated for saliva reduction in patients with ALS for 8-12 weeks.

Motor impairments in stroke survivors are prevalent and contribute to dependence in daily activities, pain and overall disability, which can further upper-limb disability. Treatment with botulinum toxin A (BoNT-A) is indicated for focal spasticity and requires knowledge of biomechanics and anatomy to best select muscles to be injected in the limb. OBJECTIVE We aimed to describe the frequency of posture patterns in a Brazilian sample of stroke survivors and correlate them with recommendations of muscle selection for treatment with BoNT-A. METHODS Fifty stroke patients with spastic upper limbs scheduled for neuromuscular block were photographed and physically examined, to be classified by three independent evaluators according to Hefter's classification. Muscles that were injected with BoNT-A by their routine doctors were retrieved from medical charts. RESULTS Pattern III and IV were the most common (64.7%, 21.6%). We further subclassified pattern III according to the rotation of the shoulder, which effectively interfered in muscle choice. The muscles most frequently treated were shoulder adductors and internal rotators, elbow flexors and extensors, in forearm, the pronator teres and finger and wrist flexors, and, in the hand the adductor pollicis. CONCLUSION Frequencies of upper-limb postures differed from previous reports. Other clinical features, besides spasticity, interfered with muscle choice for BoNT-A injection, which only partially followed the recommendations in the literature.

Introduction: Adductor spasmodic dysphonia (ADSD) is one of the most disabling voice disorders with no permanent cure. Patients with ADSD suffer from poor voice quality and repeated interruption of phonation that leads to limitations in daily communication. Botox (BT) injection, considered the gold standard treatment for ADSD, reduces the amount of voice breaks and improves voice quality for a limited period. In this study, patients with ADSD were followed after a single BT injection to track the changes in QOL and perceptual voice quality over a 6-month period., Method: This is a prospective and longitudinal study. Fifteen patients with ADSD were evaluated preinjection and 1, 3, and 6 months postinjection. They completed the Voice Activity and Participation Profile-Persian Version (VAPPP) and read a passage at each recording period. Perceptual assessment was done by three expert speech-language pathologists with knowledge of ADSD using the grade, roughness, breathiness, asthenia, strain (GRBAS) scale. The data were analyzed using Friedman, Wilcoxon, and McNemar tests. The significance level was set at P < 0.05., Results: The VAPPP total score and each of the domain scores reached their peak scores at 3 months postinjection. At 6 months postinjection, the VAPPP scores increased significantly in comparison with the 3-month scores and but were lower than preinjection scores. GRBAS results also indicated that patients' voices at 1 and 3 months postinjection were significantly less severe in terms of strain and roughness (P = 0.01; P < 0.001, respectively)., Conclusion: BT injection resulted in improvement of subjects' QOL. The improvement was greatest at 3 months postinjection but remained above the preinjection values at 6 months after injection. The voice quality also improved but was not judged as normal., (Copyright © 2018 The Voice Foundation. All rights reserved.)

Objective: To present the results our active management protocol for bothersome overactive bladder (OAB) symptoms using abobotulinumtoxinA (Dysport) over a 9-year period., Material and Methods: Data from consecutive patients with OAB symptoms due to urodynamically-proven idiopathic detrusor overactivity who had failed maximum-dose pharmacotherapy and bladder drill were reviewed. All patients completed the Overactive Bladder Symptom Score (OABSS) and Likhart quality of life indices before treatment and again at review 6 weeks post-treatment. Two hundred and fifty units of abobotulinumtoxinA were injected under general anaesthesia. Repeat treatment was offered only after failed resumption of pharmacotherapy with bladder drill., Results: The results of 299 treatments in 170 patients were reviewed. OABSS and quality of life indices improved by a mean of 35% (P ˂.001) and 41% (P ˂.001), respectively, with the OABSS improving by 2 or more points in 65% of cases. While urgency incontinence was completely abolished in 26%, the severity of incontinence was reduced in 44%. Pharmacotherapy was resumed after a mean of 10.2 months, and the mean interval between repeat abobotulinumtoxinA injection treatments was 21.3 months. De-novo self-catheterization was required in 18.2% of cases due to high postvoid residuals., Conclusion: The use of abobotulinumtoxinA is safe and highly effective treatment option for patients with refractory OAB symptoms. Our data show similar outcomes to onabotulinumtoxinA in terms of symptom score improvement and self-catheterization rates., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose of Review: This article provides a summary of the state of the art in the diagnosis, classification, etiologies, and treatment of dystonia., Recent Findings: Although many different clinical manifestations of dystonia have been recognized for decades, it is only in the past 5 years that a broadly accepted approach has emerged for classifying them into specific subgroups. The new classification system aids clinical recognition and diagnosis by focusing on key clinical features that help distinguish the many subtypes. In the past few years, major advances have been made in the discovery of new genes as well as advances in our understanding of the biological processes involved. These advances have led to major changes in strategies for diagnosis of the inherited dystonias. An emerging trend is to move away from heavy reliance on the phenotype to target diagnostic testing toward a broader approach that involves large gene panels or whole exome sequencing., Summary: The dystonias are a large family of phenotypically and etiologically diverse disorders. The diagnosis of these disorders depends on clinical recognition of characteristic clinical features. Symptomatic treatments are useful for all forms of dystonia and include oral medications, botulinum toxins, and surgical procedures. Determination of etiology is becoming increasingly important because the number of disorders is growing and more specific and sometimes disease-modifying therapies now exist.

Background:  The present study aimed to evaluate and compare the efficacy of botulinum toxin type A (BTX-A) injection versus thoracic sympathectomy for idiopathic palmar hyperhidrosis., Methods:  Fifty-one patients with idiopathic palmar hyperhidrosis were treated with either BTX-A injection or thoracic sympathectomy between March 2013 and April 2016. The severity of palmar hyperhidrosis was qualitatively measured via the Hyperhidrosis Disease Severity Scale (HDSS). All patients completed a questionnaire that detailed the time taken for the treatment to work, local or systemic adverse effects, and pre- and post-treatment severity of hyperhidrosis. The efficacy and adverse effects of the two treatments were compared and analyzed., Results:  Hyperhidrosis-related quality of life improved quickly and significantly in the BTX-A group (26 patients) and the sympathectomy group (25 patients). Compared with pre-treatment, the HDSS score significantly reduced after treatment in both groups ( p  < 0.05). All patients in the sympathectomy group had cessation of sweating of the hands after treatment, and this curative effect lasted for 12 months. In contrast, the treatment took more time to work in the BTX-A group, and the curative effect lasted for a much shorter period (3 months). The sympathectomy group had a significantly lesser mean HDSS score than the BTX-A group at 1 week, 3 months, 6 months, 9 months, and 12 months after treatment ( p  < 0.05). The sympathectomy group experienced more complications than the BTX-A group., Conclusion:  For palmar hyperhidrosis, thoracic sympathectomy is more effective and has a longer lasting curative effect than BTX-A injection, but thoracic sympathectomy has more complications., Competing Interests: None., (Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: Treatment with botulinum toxin A is the evidence-based first-line therapy of cervical dystonia. The aim of this study was to analyze long-term data of the most commonly used products concerning safety and efficacy in a big cohort over decades., Methods: We retrospectively analyzed the treatment data of all cervical dystonia patients in our outpatient clinic having at least three treatment sessions with current onabotulinumtoxinA or abobotulinumtoxinA. The observation period was up to 17 years for onabotulinumtoxinA and 27 years for abobotulinumtoxinA. We report on safety and efficacy, comparing parameters such as dose, treatment intervals, side effects, occurrence and reasons of primary or secondary non-response., Results: We analyzed a total of 2592 and 6660 treatment sessions in 135 patients with onabotulinumtoxinA, 209 with abobotulinumtoxinA and 10 having received both preparations. We found a moderate increase of dosage in the first years which was succeeded by a stable mean dose (138 and 663 mouse units, respectively) and stable injection intervals from the beginning. The most frequent side effects were mild dysphagia (2/6%), muscle weakness (2/6%) and pain (2/2%). Reasons for therapy discontinuation were change to a nearby doctor, age, other diseases, spontaneous improvement, side effects or possible treatment failure. Of all patients, only two tested positive for neutralizing antibodies against botulinum toxin A., Conclusion: We show that treatment of cervical dystonia with the two most frequently used botulinum toxin A preparations is a safe and effective therapy even over a long treatment duration of up to 27 years.