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This study aims to analyze and discuss recent trials of high-dose and liquid toxins for treating moderate to severe glabellar lines. A comprehensive review of clinical studies and patient outcomes data was conducted to assess the effectiveness and safety profiles of high-dose and liquid toxins. Clinical studies have demonstrated that high-dose toxins provide prolonged muscle relaxation and reduced wrinkles, with well-tolerated safety profiles. Liquid toxins offer comparable efficacy to traditional formulations with quicker onset and extended duration of effects. The introduction of high-dose and liquid toxins represents a significant advancement in esthetic medicine, providing patients with more options for achieving natural-looking, long-lasting results., Competing Interests: Disclosure Dr M. H. Gold does research and consulting services for Allergan Aesthetic, Galderma, Merz, Evolus, Revance, Hugel/Croma., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Driven by the clinical success of botulinum toxin serotype A (BoNT/A) and the need for improved chronic pain management, researchers attempted to develop re-designed botulinum toxin (BoNT)-based molecules as novel analgesics. Various recombinant protein expression strategies including retargeted binding domains, and chimeric toxins combining different serotypes were tested to improve BoNT/A therapeutic safety margin and expand its efficacy. The aim of this review is to re-evaluate the current design strategies for recombinant BoNT-based molecules for pain treatment, compares their analgesic profile against the native BoNT/A, as well as to discuss the main strengths and potential weaknesses of reported approaches., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

By-products like CO₂ and organic acids, produced during Clostridium botulinum growth, appear to inhibit its development and reduce ATP production. A decrease in ATP production creates an imbalance in the ATP/GTP ratio. GTP activates CodY, which regulates BoNT expression. This toxin is released into the extracellular medium. Its light chains act as a specific endopeptidase, targeting SNARE proteins. The specific amino acids released enter the cells and are metabolized by the Stickland reaction, resulting in the synthesis of ATP. This ATP might then be used by histidine kinases to activate Spo0A, the main regulator initiating sporulation, through phosphorylation., Competing Interests: Declaration of competing interest No conflict of interest., (Copyright © 2024 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Movement disorders such as cervical dystonia, blepharospasm, and hemifacial spasm negatively impact the quality of life of people living with these conditions. Botulinum toxin (BoNT) injections are commonly used to treat these disorders. We sought to describe patient characteristics, BoNT utilization, and potential adverse events (AEs) among patients with cervical dystonia, blepharospasm, and hemifacial spasm using Optum's de-identified Clinformatics ® Data Mart Database. Patients were required to have a diagnosis of the specific condition plus evidence of treatment with BoNT between 8/1/2010 and 5/31/2022. Cervical dystonia patients were commonly females (76%) and aged 45 and older (78%); both blepharospasm and hemifacial spasm patients were commonly females (both 69%) and aged 65 and older (61% and 56%, respectively). Anticholinergics were commonly used (65-82% across cohorts), as were peripheral muscle relaxants for cervical dystonia patients specifically (31%). The median number of injections per year was 2 with the median weeks between injections being between 13 and 15. Of the AEs evaluated, dyspnea was identified frequently across all the cohorts (14-20%). The findings were similar for different BoNT formulations. More research is needed to thoroughly describe BoNT utilization, such as the doses injected, and to optimize treatment for patients with these conditions.

Background: Moving Ear Syndrome is a rare hyperkinetic disorder., Phenomenology Shown: This Video Abstract illustrates typical backward movements of the right ear associated with pain and discomfort in a man with Moving Ear Syndrome., Educational Value: Moving Ear Syndrome is effectively and safely treatable with EMG-US-guided botulinum toxin injections., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Continuous fasciculation that occurs without weakness is referred to as benign fasciculation. Although generally considered non-threatening, cases that persist can significantly impact an individual's quality of life. This study presents a case of a male patient in his 30s experiencing unyielding twitching localized to the sole of his left foot for 2 years. His medical history was devoid of any notable neuromuscular diseases. Results from electromyography testing were also normal for all parameters. Attempts with pharmacological intervention did not yield any improvement of his condition. Although a nerve block targeting the left tibial nerve managed to reduce the severity of the twitching, it failed to decrease its frequency or provide a lasting solution. In search of a more effective treatment, botulinum toxin was administered via ultrasound guidance into the flexor hallucis and digitorum longus muscles. This approach resulted in a marked reduction in both the frequency and severity of the twitching, enabling the patient to resume his daily activities and achieve restful sleep without experiencing any adverse effects. Through this case, the efficacy of botulinum toxin injections as a treatment for intractable twitching is underscored, offering valuable insights into potential therapeutic strategies for similar clinical presentations., Competing Interests: Declaration of conflicting interestThe authors declare that there are no conflicts of interest.

Botulinum toxin (BonT) is the mainstream treatment option for post-stroke spasticity. BoNT therapy may not be adequate in those with severe spasticity. There are a number of emerging treatment options for spasticity management. In this paper, we focus on innovative and revived treatment options that can be alternative or complementary to BoNT therapy, including phenol neurolysis, cryoneurolysis, and extracorporeal shock wave therapy., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: There are 7 known serotypes of botulinum neurotoxins (A through G). Currently, commercially available toxins are those in serotypes A and B. This paper will discuss new toxins on the horizon, developments in prolonging and shortening the duration of outcomes, and novel therapeutic indications on the horizon., Objective: To provide insight into new toxins and new therapeutic modalities surrounding toxins on the horizon., Methods: The authors have reviewed the relevant literature and shared their insights and opinions as to future developments in toxin research and potential clinical applications., Conclusion: Botulinum neurotoxin type E's faster onset and shorter duration of effect represent true clinical differentiators. Future development of botulinum neurotoxin type E for aesthetic and therapeutic uses will be in areas where fast onset and short duration of effect are desirable. Current challenges with neuromodulators include the need for frequent treatments and lack of reversal agents. Agents to address both challenges and novel indications, including inhibition of melanogenesis, are being developed., (Copyright © 2024 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Botulinum neurotoxins produced by Clostridium botulinum consist of a complex of a core neurotoxin protein and one or more nontoxin accessory proteins. The accessory proteins are generally thought to protect the neurotoxin from the gastric environment in botulism poisoning, dissociating away upon absorption. Other than their questionable immunogenicity, they are rarely mentioned in botulinum toxin therapy., Objective: To review evidence that accessory proteins potentially play a role in neurotoxin activity., Results: Evidence suggests that the accessory proteins do not dissociate from the neurotoxin complex and enhance neurotoxin activity. Complexed type A botulinum toxin has dramatically higher endopeptidase activity than noncomplexed neurotoxin. A primary accessory protein, hemagglutinin-33, exhibits this same effect on both type A and type E core neurotoxin proteins, the latter not natively having this accessory protein. A clinical study using an objective computer assessment assay has shown a correlation between type A complex size and glabellar strain reduction, which reflects increasing clinical efficacy. Finally, a systematic review found no correlation between type A complex size and neutralizing antibody formation., Conclusion: Accessory proteins may play a role in the efficacy of botulinum toxin and could remain complexed to the neurotoxin for longer than previously reported., (Copyright © 2024 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Botulinum neurotoxins (BoNTs) are valuable tools to unveil molecular mechanisms of exocytosis in neuronal and non-neuronal cells due to their peptidase activity on exocytic isoforms of SNARE proteins. They are produced by Clostridia as single-chain polypeptides that are proteolytically cleaved into light, catalytic domains covalently linked via disulfide bonds to heavy, targeting domains. This format of two subunits linked by disulfide bonds is required for the full neurotoxicity of BoNTs. We have generated a recombinant version of BoNT/B that consists of the light chain of the toxin fused to the protein transduction domain of the human immunodeficiency virus-1 (TAT peptide) and a hexahistidine tag. His6-TAT-BoNT/B-LC, expressed in Escherichia coli and purified by affinity chromatography, penetrated membranes and exhibited strong enzymatic activity, as evidenced by cleavage of the SNARE synaptobrevin from rat brain synaptosomes and human sperm cells. Proteolytic attack of synaptobrevin hindered exocytosis triggered by a calcium ionophore in the latter. The novel tool reported herein disrupts the function of a SNARE protein within minutes in cells that may or may not express the receptors for the BoNT/B heavy chain, and without the need for transient transfection or permeabilization., (© 2024 The Author(s).)

Botulinum toxin (BTX) injections into the musculature surrounding the brachial plexus have been examined as a potential treatment for neurogenic thoracic outlet syndrome (nTOS). This systematic review identified 15 publications, of which one was a randomized controlled trial. BTX injections performed with ultrasound or electromyographic guidance, and with the inclusion of the pectoralis minor muscle, in addition to the anterior and/or middle scalenes, tended to provide greater symptom improvement and may predict response to first rib resection. Importantly, most studies were of low quality; thus, the results should be interpreted with caution. Further high-quality studies are needed to confirm these findings., (© 2024 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.)

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!

Aim: To analyze the scientific production related to the use of botulinum toxin (BTX-A) in the management of bruxism and evaluate its scope, impact, networks, and new research trends., Materials and Methods: A descriptive and retrospective study of publications indexed in Scopus from January 2018 to May 2024 was conducted. The bibliometric indicators evaluated were a number of publications, citations, h-index, SCImago Journal Rank 2022, CiteScore 2022, Lotka's Law, Bradford's Law, and keyword co-occurrence analysis. Data were processed using SciVal and VOSviewer., Results: We obtained 98 publications, including original articles, reviews, and other types of documents. Among the most productive authors, most were from South Korea and Turkey. Wonkwang University (South Korea) had the highest number of publications, while Baylor College of Medicine (USA) had the highest impact with 66.5 citations per publication. Toxins had the highest number of publications and the best Cite Score in 2022. Six main topics related to BTX-A in bruxism were identified, highlighting "reviews," "electromyography" and "controlled clinical trials"., Conclusions: The use of BTX-A for the treatment of bruxism has generated increasing interest and scientific output in recent years, especially in South Korea and Brazil. However, there is a disparity in the productivity of authors, with most authors presenting only one publication., Clinical Significance: This study highlights the need for further research and collaborations to optimize clinical practice and better understand the efficacy and management of BTX-A for treating bruxism. How to cite this article: Villanueva-García M, Ruck-Sanchez N, Tinedo-López PL, et al. Bibliometric Analysis of Botulinum Toxin and Bruxism: Impact, Visualization, and Collaborative Networks. J Contemp Dent Pract 2024;25(6):599-604.

Background and Objectives: Botulinum neurotoxin (BoNT) is a substance used to treat chronic sialorrhea, muscle dystonia, and is used in cosmetic applications. Measuring the potency of BoNT is crucial because it acts even with a small amount. However, the current methods for measuring the potency of BoNT involve using two-dimensional neuroblastoma cell line-based methods. In this study, we aimed to develop a new method to measure the potency of BoNT using a three-dimensional organoid culture system., Materials and Method: We established the optimal conditions for coculturing N2a neuronal cells with murine salivary gland organoids (SGOs). After determining the appropriate chemical concentrations, we treated the SGOs cocultured with N2a cells with BoNT type A (BoNT/A). We confirmed the expression of salivary gland-related genes and proteins using real-time polymerase chain reaction (PCR) and immunofluorescence staining., Results: The SGOs cocultured with N2a cells showed that the dendrites or axons of neuronal cells were in contact with the outermost layer of the SGOs. When we applied acetylcholine and neostigmine to the coculture systems, the mRNA expression of Aqp5 and Bhlha15, associated with salivary gland secretory cells, increased. However, this effect was reversed when BoNT/A was applied, as confirmed through real-time PCR., Conclusion: We found that the coculture system of SGOs and N2a neuronal cells can potentially serve as a potency testing platform for BoNT., Level of Evidence: NA Laryngoscope, 134:2697-2704, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: The current body of research on utilizing botulinum toxin (BTX) to manage temporomandibular disorders (TMDs) has not yet yielded definitive conclusions. The primary objective of this study was to determine the effectiveness of BTX in pain reduction for TMDs compared to placebo and other treatments. The secondary outcomes evaluated were adverse events, maximum mouth opening, bruxism events, and maximum occlusal force., Materials and Methods: A literature search was performed on PubMed, Dimension Publication, Scopus, and Google Scholar. The RoB 2 tool was used for quality assessment. The mean differences in pain scores were estimated to measure the effect of BTX on pain reduction. For adverse events, the risk ratio for the incidence of side effects was calculated., Results: Two hundred and sixty non-duplicate articles were identified; however, only 14 RCTS were included in this review. The total study population included 395 patients. The overall risk of bias showed a low to moderate quality of evidence. Results from 6 studies were reported only narratively; four studies were used for meta-analysis on pain reduction, and five were used for meta-analysis on adverse events. The control used in the meta-analysis was placebo injections. Results of the meta-analysis for pain reduction were statistically insignificant for the BTX group with mean differences at MD = -1.71 (95% CI, -2.87 to -0.5) at one month, -1.53 (95% CI, -2.80 to -0.27) at three months, and -1.33 (95% CI, -2.74 to 0.77) at six months. This showed that BTX treatment was not significantly better than placebo for a reduction in pain scores at 1, 3, and 6 months. Regarding safety, the placebo group showed a relative risk of 1.34 (95%CI, 0.48-6.78) and 1.17 (95%CI, 0.54-3.88) at 1 and 3 months respectively. However, the risks were not statistically significant. There was also no difference in the effectiveness of BTX compared to placebo and other treatments for maximum mouth opening, bruxism events, and maximum occlusal force., Conclusion: BTX was not associated with better outcomes in terms of pain reduction, adverse events, maximum mouth opening, bruxism events, and maximum occlusal force. More high-quality RCTs are needed to better understand this topic., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 Saini et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Objective: Myofascial pain syndrome (MPS) is a chronic musculoskeletal disorder characterized by the presence of trigger points. Among the treatment options, botulinum toxin injections have been investigated. The aim of this paper was to provide a synthesis of the evidence on intramuscular botulinum toxin injections for upper back MPS., Databases and Data Treatment: A systematic review of the literature was performed on the PubMed, Scopus and Cochrane Library, using the following formula: ("botulinum") AND ("musculoskeletal") AND ("upper back pain") OR ("myofascial pain")., Results: Ten studies involving 651 patients were included. Patients in the control groups received placebo (saline solution) injections, anaesthetic injections + dry needling or anaesthetic injections. The analysis of the trials revealed modest methodological quality: one "Good quality" study, one "Fair" and the other "Poor". No major complications or serious adverse events were reported. Results provided conflicting evidence and did not demonstrate the superiority of botulinum toxin over comparators. Most of the included trials were characterized by a small sample size, weak power analysis, different clinical scores used and non-comparable follow-up periods. Even if there is no conclusive evidence, the favourable safety profile and the positive results of some secondary endpoints suggest a potentially beneficial action in pain control and quality of life., Conclusion: The currently available studies show conflicting results. Their overall low methodological quality does not allow for solid evidence of superiority over other comparison treatments. Further insights are needed to properly profile patients who could benefit more from this peculiar injective approach., Significance: The randomized controlled trials included in this review compared using botulinum toxin to treat upper back MPS with placebo or active treatments (e.g., dry needling or anaesthetics) showing mixed results overall. Despite the lack of clear evidence of superiority, our study suggests that the use of botulinum toxin should not be discouraged. Its safety profile and encouraging results in pain control, motor recovery and disability reduction make it an interesting treatment, particularly in the subset of patients with moderate to severe chronic pain and active trigger points. To support the safety and efficacy of botulinum toxin, further high-quality studies are needed., (© 2023 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC ®.)

Objective: Botulinum toxin (Btx) therapy has emerged as a potential treatment for patients with Raynaud phenomenon (RP) in recent years. This study aimed to investigate the efficacy and safety of Btx treatment for RP., Methods: Databases of PubMed, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from their inception up to August 2022. Studies that reported Btx use for the treatment of RP were included. A meta-analysis was conducted for the Shortened version of the Disabilities of the Arm, Shoulder, and Hand (Quick DASH) score and visual analog scale pain score using a random-effects model., Results: Thirteen full-text studies were included. The pooled standard mean changes for the visual analog scale pain score and QuickDASH score were -3.82 (95% confidence interval, -6.62 to -1.02) and 0.83 (95% confidence interval, -1.47 to -0.19), respectively. The 2 most common complications were injection site pain and intrinsic hand weakness., Conclusions: The effect of Btx treatment on RP is promising based on current evidence. Nevertheless, more studies and randomized clinical trials with larger sample sizes are needed to confirm the current results., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The efficacy of botulinum toxin injection for the treatment of third, fourth, and sixth nerve palsy was evaluated. PubMed, Scopus, EMBASE, Web of Science, and Google Scholar databases were searched. Data about the duration of palsy (acute vs chronic), cause of the palsy, type of toxin used, mean dose, and other background characteristics were collected. Outcome variables were success rate (defined by alleviation of diplopia or reduction in eye deviation) and standardized mean difference of prism diopter and abduction deficit before and after injection. The Joanna Briggs Institute checklist was implemented for the risk of bias assessment. The analysis included 38 articles, comprising 643 patients. The overall treatment success rate in acute and chronic nerve palsy was 79% and 33%, respectively. The success rate was not significantly different between different subgroups of age, type of botulinum toxin, pre-injection prism diopter, etiology of the palsy, duration of follow-up, and mean dose of botulinum toxin injection. However, in both acute and chronic palsy, diabetes etiology was accompanied by the highest success rate. Overall symptomatic response to botulinum injection was 84% (95% CI: 67% to 96%), whereas functional response was observed in 64% (95% CI: 47% to 79%) of the patients. The odds ratio for the success rate of treatment of palsies with botulinum toxin versus expectant management was 2.67 (95% CI: 1.12 to 6.36) for acute palsy and 0.87 (95% CI: 0.17 to 4.42) for chronic palsy. Botulinum toxin can be used for the treatment of acute third, fourth, and sixth nerve palsy, especially in patients with acute palsy and more severe tropia. [ J Pediatr Ophthalmol Strabismus . 2024;61(3):160-171.] .

Background: Botulinum type-A toxin is a well established aesthetic and medical treatment. While the usage of type-B toxin is less common, there is a growing interest in using type-B toxin, especially in those who are treatment resistant., Objective: To evaluate the primary FDA-approved clinical applications of rimabotulinumtoxinB, along with established and emerging off-label clinical indications., Material and Methods: Articles were reviewed from PubMed database and Food and Drug Adminstration guidelines., Results: Facial rhytids tend to use a higher conversion ratio between type A and type B toxin, due to type B toxin's weaker affinity to muscles and higher affinity for sweat glands. Specially, a 1:100 to 1:50 ratio was utilized for glabellar rhytids, a 1:25 to 1:50 ratio for periocular rhytids, a 1:50 to 1:66.6 ratio for cervical dystonia, a 1:20 to 1:50 ratio for hyperhidrosis, and a 1:25 to 30 ratio for sialorrhea., Conclusion: Type B toxin has demonstrated its safety and efficacy in treating facial rhytids, cervical dystonia, sialorrhea and hyperhidrosis, with potential for novel applications under investigation. Regardless of injection location and clinical applications, dry mouth and dysphagia remained the most common side effects. Across all indications, type B toxin appeared to have a faster onset of action, a dose-dependent clinical duration, and a dose-dependent adverse effect profile., (Copyright © 2024 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Upper and lower limb spasticity is commonly associated with central nervous system disorders including stroke, traumatic brain injury, multiple sclerosis, cerebral palsy, and spinal cord injury, but little is known about the concurrent treatment of upper and lower limb spasticity with botulinum toxins., Objective: To evaluate onabotulinumtoxinA (onabotA) utilization and to determine if concurrent onabotA treatment of the upper and lower limbs has supported improvements in participants with spasticity., Design: Sub-analysis of a 2-year, international, prospective, observational registry (ASPIRE, NCT01930786)., Setting: International clinic sites (54)., Participants: Adult spasticity participants across etiologies, who received ≥1 concurrent onabotA treatment of the upper and lower limbs during the study., Intervention: Participants were treated with onabotA at the clinician's discretion., Outcomes: Baseline characteristics and outcomes of disability (Disability Assessment Scale [DAS]), pain (Numeric Pain Rating Scale [NPRS]), participant satisfaction, physician satisfaction, and quality of life (QoL; Spasticity Impact Assessment [SIA]) were evaluated. Adverse events were monitored throughout the study., Results: Of 744 participants enrolled, 730 received ≥1 dose of onabotA; 275 participants received treatment with onabotA in both upper and lower limbs during ≥1 session; 39.3% of participants were naïve to onabotA for spasticity. The mean (SD) total dose per treatment session ranged from 421.2 (195.3) to 499.6 (188.6) U. The most common baseline upper limb presentation was clenched fist (n = 194, 70.5%); lower limb was equinovarus foot (n = 219, 66.9%). High physician and participant satisfaction and improvements in pain, disability and QoL were reported after most treatments. Nine participants (3.3%) reported nine treatment-related adverse events; two participants (0.7%) reported three serious treatment-related severe adverse events. No new safety signals were identified., Conclusion: More than a third of enrolled participants received at least one concurrent onabotA treatment of the upper and lower limbs, with reduced pain, disability, and improved QoL after treatment, consistent with the established safety profile of onabotA for the treatment of spasticity., (© 2024 The Authors. PM&R published by Wiley Periodicals LLC on behalf of American Academy of Physical Medicine and Rehabilitation.)

Introduction: Botulinum neurotoxin (BoNT) injections are widely used for the treatment of masseter muscle hypertrophy in Southeast Asia. However, there remains a lack of consensus regarding the optimal injection technique. This study aimed to compare the efficacy and patient discomfort associated with single-entry point injections versus multiple three-point injections for masseter muscle hypertrophy treatment with BoNT., Materials and Methods: Sixteen participants, comprising both male and female Korean adults aged 22-63, were enrolled in the study. On the left side of the face, single-entry point injections were administered, followed by multidirectional injections, while on the right side, three-point injections were given. Pain intensity during the procedure was assessed using visual analogue scale scores., Result: Our results revealed that participants experienced lower levels of pain with single-entry point injections compared to three-point injections (average visual analogue scores of 3.31 and 5.19, respectively)., Conclusion: These findings highlight the potential benefits of single-entry point injections in reducing patient discomfort during masseter muscle hypertrophy treatment with BoNT. We advocate for further research to validate these findings and encourage practitioners to consider single-entry point injections as a viable option for enhancing treatment outcomes in their clinical practice., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

The first-line management of cervical dystonia (CD) symptoms is intramuscular injection of botulinum toxin type A (BoNTA). However, a comparison of safety among BoNTAs is difficult because, per regulatory authorities, units of BoNTA activity are not interchangeable. Dysphagia and muscle weakness are widely considered two key adverse events to monitor closely in the treatment of CD. This integrated analysis compared the safety of BoNTAs approved for CD in the US by evaluating relationships between the incidence of dysphagia and muscle weakness in prescribing information and the core neurotoxin content. Coefficients The coefficients of determination (R 2 ) and trendlines were estimated via regression-based lines of best fit. Adverse drug reaction (ADR) rates were strongly correlated with core neurotoxin amounts for conventional BoNTAs (slope coefficients: dysphagia = 0.048, R 2 = 0.74; muscle weakness = 0.096, R 2 = 0.82). The published ADR rates at approved doses for conventional BoNTAs were higher compared with DaxibotulinumtoxinA (DAXI; DAXXIFY ® , Revance Therapeutics, Inc., Nashville, TN, USA) by core neurotoxin content. The use of a core neurotoxin amount was found to be an effective method for comparing the safety of BoNTA products. Current clinical trials suggest that DAXI, a novel BoNTA formulation, provides a potentially wider safety margin compared with other approved BoNTAs for CD. The lower amount of core neurotoxin administered at approved doses compared with conventional BoNTAs may explain low on-target ADRs like muscle weakness, whereas reduced diffusion from the injection site is thought to be responsible for low off-target ADRs like dysphagia.

Botulinum neurotoxin (BoNT), produced by Clostridium botulinum , is the most toxic protein known, capable of causing severe paralysis and posing a significant bioterrorism threat due to its extreme lethality even in minute quantities. Despite this, there are currently no FDA-approved vaccines for widespread public use. To address this urgent need, we have developed an innovative vaccine platform by fusing the neuronal binding domain of BoNT/E (Hc/E) with core-streptavidin (CS), resulting in a stable CS-Hc/E vaccine. Mice vaccinated with CS-Hc/E exhibited superior antibody titers compared to those receiving Hc/E alone. To develop a trivalent vaccine against BoNT/A, BoNT/B, and BoNT/E- key contributors to the vast majority of human botulism-we conjugated CS-Hc/E with a biotinylated atoxic chimeric protein incorporating neutralizing epitopes from BoNT/A and BoNT/B. This chimeric protein includes the binding domain of BoNT/A, along with the protease-inactive light chain and translocation domains of BoNT/B. The interaction between CS and biotin formed a stable tetrameric antigen, EBA. Vaccination with EBA in mice elicited robust antibody responses and provided complete protection against lethal doses of BoNT/A, BoNT/B, and BoNT/E. Our findings highlight EBA's potential as a stable and effective broad-spectrum vaccine against BoNT. Moreover, our technology offers a versatile platform for developing multivalent, stable vaccines targeting various biological threats by substituting the BoNT domain(s) with neutralizing epitopes from other life-threatening pathogens, thereby enhancing public health preparedness and biodefense strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Liu, Liu, Chen, Yu, Meng and Wang.)

Background: Botulinum toxin A (BoNT-A) is widely used in treating dystonia and spasticity to managing chronic migraine and cosmetic applications. However, its immunogenic potential presents challenges, such as the development of neutralizing antibodies that lead to diminished therapeutic efficacy over time, known as secondary nonresponse., Objective: This review aims to bridge the knowledge gap regarding the immunogenic mechanisms of BoNT-A and to explore effective management strategies to mitigate these immune responses., Materials and Methods: The authors conducted a systematic search in databases including PubMed, Embase, and Web of Science, using keywords related to BoNT-A's immunogenicity. The selection process refined 157 initial articles down to 23 relevant studies, which underwent analysis to investigate the underlying mechanisms of immunogenicity and the factors influencing it., Results: The analysis revealed that both the neurotoxin component and the neurotoxin-associated proteins could elicit an immune response. However, only antibodies against the core toxin influence therapeutic outcomes. Various patient-specific factors such as genetic predispositions and prior immune experiences, along with treatment-related factors such as dosage and frequency, play crucial roles in shaping these responses., Conclusion: Understanding the specific immunogenic triggers and responses to BoNT-A is critical for optimizing treatment protocols and improving patient outcomes., (Copyright © 2024 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Botulinum toxin A (BoNT-A) treatment has many uses in dermatology. Its mechanism of action and long-term effects for scar formation, rosacea, and antiaging are still being investigated., Objective: To conduct a literature review on BoNT-A to further investigate its use in scar formation, rosacea, and antiaging., Methods: A literature review was conducted using PubMed on botulinum toxin treatment for scar formation, rosacea, and antiaging. Studies discussing the toxin mechanism of action and treatment algorithm were included. The authors also provided their personal experience in BoNT-A use for these 3 conditions., Results: The mechanism of action of Botulinum toxin A in improving scar formation, rosacea, and antiaging is now better understood. While it is effective in the short term, little is still known about how frequently treatment needs to be repeated and if there are any long-term effects., Conclusion: While in vitro studies have supporting evidence on the mechanism of action of BoNT-A on scar formation, rosacea, and antiaging, further studies are needed to identify long-term treatment effects., (Copyright © 2024 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

OnabotulinumtoxinA (BTX-A) was first linked to beneficial effects in migraine 25 years ago and was approved by the FDA for preventive treatment of chronic migraine in 2010. The treatment has since had a major impact on the well-being of people with chronic migraine. The clinical development programme for BTX-A and research since its approval have provided insights into the neuromodulatory sensory effect of BTX-A, how it can control chronic migraine despite its peripheral action, and the underlying biology of migraine as a disease. In this Review, we consider the impact that BTX-A has had on the management of chronic migraine and on the research field. We discuss the insights provided by clinical research, encompassing the clinical trials and subsequent real-world evidence, and the mechanistic insights provided by preclinical and translational research. We also provide an overview of future directions of research in the field BTX-A in migraine and the clinical translation of this research., (© 2024. Springer Nature Limited.)

Background: Botulinum neurotoxin type A (BoNT-A) is well-established for treatment of glabellar lines (GLs), and mostly formulated as powders requiring reconstitution for injection. The approved liquid formulation, ready-to-use (RTU) abobotulinumtoxinA was developed to ease injection procedures and prevent reconstitution errors. This multicenter, open-label, Phase IV study evaluated GL treatment experience using RTU abobotulinumtoxinA versus powder BoNT-A (onabotulinumtoxinA)., Methods: Females with experience of BoNT-A facial treatment were randomized 2:1 to GL treatment with 50 U RTU abobotulinumtoxinA (N = 99) or 20 U powder BoNT-A (N = 51) and followed-up for 6 months or 1 month, respectively. Assessments included: time to prepare each product for injection (primary endpoint); investigators' experience with product preparation/reconstitution; investigators' and subjects' treatment experience; safety; and for the RTU product: aesthetic improvement of GLs; subject satisfaction., Results: Compared with powder BoNT-A, RTU abobotulinumtoxinA required statistically significantly less preparation time (mean 0:33 vs. 1:34 min: s; p < 0.0001). Investigators preferred RTU abobotulinumtoxinA over powder BoNT-A (81% of treatment sessions) and found it allowed more time to communicate with subjects (97%). All investigators (100%) also found it easy-to-use, easy-to-learn, and that it fulfilled their expectations. Subjects found the RTU abobotulinumtoxinA treatment comfortable (91%), and through 6 months posttreatment, most reported satisfaction with their appearance (≥88%), looking natural (≥95%) and refreshed (≥80%). At Month 1, 99% of RTU-treated subjects had investigator-assessed improved aesthetic appearance in GLs, maintained in 76% at Month 6. No serious adverse events occurred., Conclusion: RTU abobotulinumtoxinA for GL treatment is well-tolerated, efficacious, shows high levels of subject satisfaction throughout 6 months, saves time, and is preferred by clinicians over powder BoNT-A., Gov Registry: NCT05277337., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Intramuscular injection of botulinum neurotoxin type A (BoNT-A) is commonly used to improve or maintain the joint range of motion in young children with spasticity. However, the effectiveness of BoNT-A treatment is variable and movement limitations are recurrent. Here we show long-term effects of a single, bilateral abobotulinumtoxinA (aboBoNT-A) injection in the gastrocnemius medialis and soleus muscles of wild-type and spastic (B6.Cg-Glrbspa/J with a mutation in the glycine receptor) mice at a young age (6-7 days). Specifically, we evaluated the impact of aboBoNT-A-A on gait, physical performance, and spontaneous physical behavior, as well as on contractile force characteristics, morphology, and histological phenotype of soleus and gastrocnemius muscles by comparing their results to those of saline-injected controls up to 9 weeks after the injection. The detailed time course of the study specifies the timing of the aboBoNT-A injection at 1 week, the period of behavioral studies from 4-9 weeks, and the age of the mice (10 weeks) at the time of contractile force characteristics and histology assessments. In spastic mice, aboBoNT-A injection had a minor and very specific effect on physical performance, by only modestly increasing stride length as a function of age. aboBoNT-A injection caused a reduction in the force-generating capacity and a slightly smaller physiological cross-sectional area in gastrocnemius medialis, but not in soleus. Reduced physiological cross-sectional area in aboBoNT-A-injected muscles was due to a lower number of muscle fibers, rather than reduced muscle fiber cross-sectional area. The percentage of slow-type muscle fibers and mitochondrial succinate dehydrogenase activity were increased, which was associated with an improved muscle endurance capacity. In conclusion, aboBoNT-A injection reduced the number of muscle fibers, causing muscle hypertrophy in remaining fibers and a shift towards more oxidative fibers, resulting in an improved endurance capacity and gait. This study proposed potential cellular mechanisms for the therapeutic efficacy of aboBoNT-A in spasticity., (© 2024 Federation of American Societies for Experimental Biology.)

Aims: One effective clinical strategy to combat obesity is intragastric botulinum toxin (BTX) injection, which increases gastric emptying time and regulates appetite. However, it remains unknown if and how BTX affects ghrelin levels., Materials and Methods: An obese animal model was established by feeding male mice with high-fat diet (HFD). BTX was administered by subserosal injection in the antrum via an upper midline laparotomy. The mice were monitored in terms of body weight and blood biochemical parameters. Glucose utility and insulin sensitivity were measured by intraperitoneal glucose and insulin tolerance tests. Additionally, stomach and liver were histologically examined after BTX treatment. AGS gastric adenocarcinoma cells were used to investigate the molecular mechanism by which BTX affects ghrelin expression., Key Findings: In HFD-fed mice, BTX injection significantly decreased both food intake and body weight over a 3-week monitoring period. Moreover, HFD-induced hyperglycemia, hyperinsulinemia, dyslipidemia and obesity readouts were improved after BTX injection. Importantly, mice also exhibited decreased plasma and gastric ghrelin levels after BTX injection. In cultured AGS cells, BTX significantly increased reactive oxygen species (ROS) levels and activated nuclear factor-κB (NF-κB), which led to decreased ghrelin expression. Pre-treatment with inhibitors of either ROS or NF-κB reversed the effects of BTX on ghrelin expression in the cultured cells., Significance: BTX decreases ghrelin expression in HFD-fed animals and in AGS cells through an ROS/NF-κB-dependent pathway. This mechanism may contribute to decreased food intake in obese subjects receiving intragastric BTX injection for weight control., Competing Interests: Declaration of competing interest We confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: RelabotulinumtoxinA (RelaBoNT-A, Galderma, Uppsala, Sweden) is an innovative, ready-to-use liquid botulinum toxin A, produced with PEARL (precipitation-free extraction and activity-preserving refined liquid) manufacturing technology, which yields a potent, complex-free formulation., Objectives: In the READY-1 study, efficacy and safety outcomes following a single RelaBoNT-A treatment for glabellar line correction were examined., Methods: Adults with moderate to severe glabellar lines received RelaBoNT-A (50 U) or placebo in a 3:1 randomized, 6-month, phase 3, multicenter, double-blind study. Primary endpoints (examined at Month 1, maximum frown) comprised the composite ≥2-grade response, defined as ≥2-grades improvement from baseline on concurrent investigator (glabellar line investigator live assessment; GL-ILA) and participant (glabellar line subject live assessment; GL-SLA) severity scales (US endpoint), and the investigator-reported responder rate for participants scored as 0 (none) or 1 (mild) (GL-ILA scale only; EU endpoint). Participant satisfaction and treatment-emergent adverse events (TEAEs) were reported., Results: Overall, 297 adults were randomized and treated. Month 1 composite ≥2-grade responder rate was 82.9% (RelaBoNT-A, n = 199) vs 0% (placebo, n = 67; P < .001). Month 1 investigator-reported none or mild responder rate was 96.3% (RelaBoNT-A) vs 4.5% (placebo; P < .001). GL-ILA scores remained higher with RelaBoNT-A (23.6% [none or mild]; 58.1% [≥1-grade improvement]) vs placebo (1.5%; 10.4%, respectively) through Month 6 (P < .001). In the Kaplan-Meier analysis, 75% still showed GL-ILA and GL-SLA improvements from baseline at 169 days (end of study). Participants reported onset of effect from Day 1 (39%) and satisfaction with natural-looking results (96.8%; Month 1). RelaBoNT-A-related TEAEs were low (3.6%) and typically mild., Conclusions: A single RelaBoNT-A treatment was effective and demonstrated a favorable safety profile. RelaBoNT-A provided significant improvements in glabellar line severity, high satisfaction, rapid onset, and enduring effectiveness throughout the 6-month study period., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Aesthetic Society.)

Hypertrophic scars arise from aberrant wound healing and can lead to functional and aesthetic impairments. One of the common interventions for treating hypertrophic scars is fractional carbon dioxide (CO2) laser, which employs narrow laser beams to stimulate dermal collagen deposition. Recent studies and reports have suggested that combining laser therapy with other interventions such as botulinum toxin type A (BTX-A) and topical growth factors may enhance treatment outcomes. Here, we examine the efficacy and safety of a sequential combination of BTX-A, fractional CO2 laser, and topical growth factors, referred to as combined therapy, for treating hypertrophic scars compared with only using fractional CO2 laser and topical growth factors, referred to as monotherapy. Our retrospective study includes 128 patients with hypertrophic scars (56 underwent monotherapy and 72 underwent combined therapy), which were followed-up for up to 15 months after the initiation of treatment to collect demographic and clinical data. Our analysis showed that the combined therapy significantly outperformed monotherapy in improving Vancouver scar scale scores (P < 0.05) and in the reduction of scar thickness (P < 0.05), without increasing adverse complications. Repeated treatments further augmented the efficacy of the combined therapy. Subgroup analysis revealed that combined therapy was notably more effective in reducing Vancouver scar scale scores and scar thickness in early-stage scars compared to late-stage (P = 0.023 and P = 0.045, respectively). Our study suggests that including BTX-A treatment before fractional CO2 laser and topical growth factors offers superior efficacy in reducing hypertrophic scars. We encourage early intervention and repeated treatments for optimal treatment outcomes., (© 2024. The Author(s).)

Botulinum neurotoxin type A (BoNT/A) is an exceptionally potent neurotoxin of great therapeutic value; however, it is also considered a weapon of mass destruction, as it is one of the most poisonous biological substances known to man. The etiology behind BoNT/A is its action as a zinc-dependent protease, which can cause extended paralysis through the cleavage of SNARE proteins. Thiosemicarbazones, known zinc chelators, provide a privileged scaffold that can be leveraged for the development of BoNT/A LC inhibitors. Through a combination of biochemical and kinetic assays, it was demonstrated that the thiosemicarbazone ZMC1, an antitumor agent, is an effective competitive inhibitor of the BoNT/A LC. Based on these results, a series of thiosemicarbazones were designed/synthesized using structure-based analysis and examined in enzyme activity and cell-based assays. From this screen, two analogues presented noteworthy cellular activity. The most potent inhibitors were then tested in a BoNT/A mouse lethality assay, providing statistically significant prolonged survival.

Botulinum injection is a well-known non-surgical intervention utilized in the management of myofascial pain syndrome (MPS). However, sparse evidence exists regarding the utility of ultrasound guidance of injectate or lidocaine as a predictive marker of patient response to botulinum toxin A (BTX-A). A 39-year-old male active duty service member demonstrated typical signs and symptoms of MPS. He reported a 10-year history of neck and back spasms that were triggered by exertion but also could occur spontaneously. Based on the characteristic regional motor-sensory defects, treatment options were discussed. With shared decision-making, the patient opted to try ultrasound-guided injection of lidocaine followed by xenomin brand BotoxA. Immediately following lidocaine injection, the patient reported complete relief of symptoms. Both injections were uncomplicated, and the patient reported great reduction in symptoms during the subsequent visit 2 months later. Relief of pain following ultrasound-guided injection of lidocaine may serve as an indicator of successful patient response to BTX-A in patients with MPS., (© The Association of Military Surgeons of the United States 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Background: Botulinum toxin (BT) has become one of the most frequently sought aesthetic procedures for wrinkle reduction., Objective: This study investigated the effectiveness and safety of a novel device using radiofrequency (RF) and high-intensity facial muscle stimulation (HIFES) in patients injected with BT., Methods: Twelve patients were divided into an Active (N=10) and a Control group (N=2), where the Active received four treatments and the Control none. The facial expressions documented by digital photographs (neutral) and videos (frown, smile, surprise expressions) were taken at all visits (baseline, after last Tx, 1 and 3-month follow-ups) and were evaluated using the Global Aesthetic Improvement Scale (GAIS) and 3D automated analysis. The subject's therapy comfort and satisfaction were assessed., Results: The Active group reported high satisfaction with treatment comfort (6.3&plusmn;0.2 points on the 7-point Likert scale). 3D analysis showed reduced wrinkle severity (37.4%) and volume increase (+1.5 mL) on the cheeks at 3 months. GAIS evaluation demonstrated the most prominent improvement in smiling facial expression by 2.2&plusmn;0.1 points. No adverse events were observed., Conclusion: The study results suggest that the combination of HIFES and synchronized RF is a safe and effective treatment for improving facial appearance and muscle tone in patients injected with BT. J Drugs Dermatol. 2024;23(11):937-942.&nbsp; doi:10.36849/JDD.7938.

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.)

Objective: To qualitatively and quantitatively summarize the evidence for the use of onabotulinumtoxinA injections in children and adolescents with migraine., Background: There are limited evidence-based treatment options for youth with migraine, especially youth with chronic migraine (CM). OnabotulinumtoxinA injections are an established evidence-based treatment for adults with CM. While several studies have assessed their safety and efficacy among adolescents with CM, there are no published systematic reviews summarizing the pediatric evidence., Methods: We carried out a systematic review, reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis, aiming to identify studies that included five or more children and adolescents aged ≤18 years with a diagnosis of migraine, who were treated with ≥50 units (U) of onabotulinumtoxinA and had outcomes assessed ≥4 weeks after one or more injection cycle. Both observational studies and randomized controlled trials (RCTs) were eligible for inclusion. Two investigators independently carried out the first (titles and abstracts) and second (full text) screening stages, as well as data extraction and quality appraisal. The American Academy of Neurology risk of bias grading scheme was used to assess study risk of bias. Studies with adequate data were pooled using random effects meta-analyses, and Hedge's g standardized mean differences with 95% confidence intervals (CIs) were generated to estimate the effect sizes of the continuous outcomes included. Studies lacking data required for meta-analysis were summarized qualitatively., Results: We screened 634 studies and included 14 studies comprising 491 participants, of whom 489 had CM. Two studies were RCTs, 12 were observational uncontrolled studies, and all but one study included only youth with CM. Five Class IV observational uncontrolled studies were amenable to pooling in meta-analyses. After a mean of 2-2.6 injection cycles, headache frequency was shown to decrease significantly after treatment with onabotulinumtoxinA (Hedge's g = 0.97, 95% CI 0.58-1.35; p < 0.0001), as did severity (Hedge's g = 1.24, 95% CI 0.55-1.94; p = 0.0005), with both estimates having a large effect size magnitude. A Class I parallel-group RCT of one injection series (155 U, 74 U, or placebo), powered to detect a change in 4 headache days per month, did not find outcome differences between the active and placebo treatment arms. A Class IV crossover RCT showed superiority of active (155 U) versus placebo injections. The remaining Class IV observational studies that were excluded from the meta-analyses all showed improved outcomes with onabotulinumtoxinA injections over time. No serious adverse events related to treatment occurred., Conclusion: OnabotulinumtoxinA injections have established safety for use in children and adolescents with CM and are likely effective in reducing headache frequency and severity over time. However, in the absence of an adequately powered parallel-group RCT assessing the efficacy of multiple injection cycles, it remains unclear if this intervention is superior to placebo., (© 2024 The Author(s). Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.)

Background: Injections of botulinum toxin type A (BoNT-A) have been proposed as an additional treatment modality for patients suffering chronic temporomandibular disorder (TMD)-related myofascial pain (MFP). BoNT-A impairs muscle function, along with its analgesic effect, and a minimal effective dose should be used. The objective of this randomized placebo-controlled crossover study was to evaluate the clinical benefit of a moderate dose (50 U) of BoNT-A., Methods: Sixty-six subjects were randomized into two groups, one which received BoNT-A first and a second which received a saline solution (SS) first. Follow-ups were performed 2, 11, and 16 weeks after the injections. Diagnostic criteria for temporomandibular disorders (DC/TMD) diagnostic algorithms were used to evaluate characteristic pain intensity (CPI) and pain-related disability based on the Graded Chronic Pain Scale (GCPS). Electromyographic and bite force were also evaluated., Results: The within-group analysis showed a significant improvement in pain intensity and pain-related disability after BoNT-A (p < 0.001, p = 0.005, p = 0.011) and SS (p = 0.003, p = 0.005, p = 0.046) injections up to week 16. The between-group analysis of pain-related variables revealed no differences between groups at any time. Nonetheless, BoNT-A, but not SS, caused a significant decline in muscle performance. The number needed to treat (NNT) regarding a clinically significant pain reduction (≥30%) was 6.3, 57.0, and 19.0 at 2, 11, and 16-week follow-ups favoring BoNT-A., Conclusions: Injections of 50 U of BoNT-A might improve MFP symptoms, but the specific effect of the drug on pain compared to the placebo is not obvious., (© 2024 The Author(s). Pain Practice published by Wiley Periodicals LLC on behalf of World Institute of Pain.)

Background: The popularity of noninvasive botulinum toxin type A (BTX-A) injections for masseter muscle hypertrophy is increasing among Asian individuals with a square-shaped lower face., Aims: This study aimed to analyze the adverse events (AEs) caused by BTX-A injections into the masseter muscle., Patients/methods: This observational study retrospectively evaluated 46 250 patients who underwent BTX-A injections into the masseter muscle in 2022. The inclusion criteria were the diagnosis of an AE by the physician at the return visit and subsequent follow-up of progress (n = 223). The patients who were lost to follow-up (n = 40) were excluded from the study., Results: Among the 223 patients with AEs, the most common AE was paradoxical bulging (88.3%, n = 197/223). The average period from treatment until confirmation of improvement was 159.6 ± 113.6 days (range 13-667 days) for all AEs, all of which were temporary. The period until improvement was 166.1 days in the intervention group (n = 122) and 151.9 days in the observation group (n = 101) (p = 0.24). As the period until improvement of AEs included the period until the patients visited the clinics and the improvements were confirmed by physicians, the actual period was likely to have been shorter., Conclusions: (1) All AEs were temporary. (2) All AEs improved within 22.2 months (within 5.3 ± 3.8 months on average). (3) There was no significant difference between the intervention and observation groups in the period until the improvement of AEs., (© 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.)

Botulinum neurotoxin (BoNT) has been in use since the 1970's. Its effect is reached mainly by inhibiting the release of acetylcholine in the synaptic gap of motor neurons or at the motor end plate and the parasympathetic ganglia. In the case of Parkinson's disease, it is used to treat several motor and non-motor symptoms. Within recent years increasingly numerous possible fields of application of BoNT have been found for the treatment of Parkinson's disease, and for some specific symptoms it has in fact become the therapy of choice, while for others it is but one of the therapeutic options that come into consideration when others are not sufficiently effective. In the following, we intend to outline the indications, the possible side effects and also the approvals for therapies with botulinum toxin in the primary and secondary symptoms of Parkinson's disease., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Premature ejaculation (PE) is a common sexual problem, resulting in adverse effects on the quality of life, of both the patient and the partner. The idea of muscular contraction inhibition during the ejection phase of ejaculation by Botulinum toxin-A injection may delay ejaculation., Aim of Study: This study was performed to assess the efficacy and safety of Botulinum toxin-A injection in PE treatment., Material and Methods: This study included 45 married male patients diagnosed with primary PE. All included patients were injected with 75 units of Dysport equal efficacy of 25 units of Botulinum toxin-A (Botox) into three sites: the root of the penis (Group 1), glans penis (Group 2), and each side of the ischiocavernosus muscle (Group 3). All patients were subjected to an assessment of intravaginal ejaculation latency time (IELT) using a stopwatch and answering the Premature Ejaculation Diagnostic Tool (PEDT) Questionnaire before and after treatment., Results: There was a statistically significant improvement in IELT after treatment in all groups. The most significant improvement was shown in Group 3 (average 108% increase), followed by Group 1 (74%) and Group 2 (40%), respectively. There was a positive correlation between age and the improvement in improved IELT. There was a statistically significant improvement in PEDTq scores in Group 1 and Group 3., Conclusion: Botulinum toxin-A injection into the root of the penis and ischiocavernosus muscle could be recommended in the treatment of premature ejaculation., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Chronic migraine encephalalgia (CME) with concomitant temporomandibular disorder (TMD) is a serious illness with limited effective treatment options. This study explores the effectiveness of onabotulinumtoxinA (BtxA) as an adjunct therapeutic to TMJ arthroscopy in the relief of CME., Methods: A retrospective cohort study of patients receiving TMJ arthroscopy, with or without BtxA injections for CME, was conducted. Variables assessed include pain using a visual analog scale (VAS), maximal incisal opening (MIO), muscle soreness, and headache frequency and duration., Results: Sixty patients (44 BtxA, 16 Control), consisting of 56 (93.3%) females, met inclusion criteria. A significant reduction in pain is reported with patients receiving BtxA ( p < 0.0001) on VAS as compared to Control group. BtxA treatment also significantly reduced headache frequency and duration ( p < 0.05)., Conclusion: These results support the use of adjunctive BtxA treatment with arthroscopy for the treatment of CME in the context of TMD.

Purpose: To compare the quality of life (QoL) in the same patients first treated with botulinum toxin A (BTA) injections for neurogenic detrusor overactivity (NDO) and then with bladder augmentation (BA)., Method: Retrospective study of patients who had BA after BTA treatment between January 2012 and December 2022. Qualiveen Short Form questionnaires and a 7-level Likert/PGI-I scale to answer the question "How would you describe your quality of life after surgery compared to when you felt your best with BTA injections?" were collated and analyzed., Results: Fifty-two BAs for neurogenic bladder (NDO or low compliance) were performed in patients with a median age of 43years [33; 52] previously treated with BTA. After a median follow-up of 33.5 [13.8; 54.3] months, the median Qualiveen-SF global score after BA was significantly higher than that obtained at best BTA efficacy (1.63 [1; 2.63] vs. 2.63 [1.88; 3], P=0.012), as were the scores for the fear, constraints/restrictions and limitations/inconvenience domains. The median PGI-I score was +3 [2; 3] (truly better QoL) and 85.4% of patients reported a QoL after BA superior to the best QoL under BTA., Conclusion: BA provides a greater range of QoL improvement than BTA injection for patients who have experienced both treatments. Long-lasting effects and absence of need to perform iterative retreatment were the main reasons., (Copyright © 2024. Published by Elsevier Masson SAS.)