From Toxin to Treatment: A Narrative Review on the Use of Botulinum Toxin for Autonomic Dysfunction.

Since its regulatory approval over a half-century ago, botulinum toxin has evolved from one of the most potent neurotoxins known to becoming routinely adopted in clinical practice. Botulinum toxin, a highly potent neurotoxin produced by Clostridium botulinum, can cause botulism illness, characterized by widespread muscle weakness due to inhibition of acetylcholine transmission at neuromuscular junctions. The observation of botulinum toxin's anticholinergic properties led to the investigation of its potential benefits for conditions with an underlying etiology of cholinergic transmission, including autonomic nervous system dysfunction. These conditions range from disorders of the integument to gastrointestinal and urinary systems. Several formulations of botulinum toxin have been developed and tested over time, significantly increasing the availability of this treatment for appropriate clinical use. Despite the accelerated and expanded use of botulinum toxin, there lacks an updated comprehensive review on its therapeutic use, particularly to treat autonomic dysfunction. This narrative review provides an overview of the effect of botulinum toxin in the treatment of autonomic dysfunction and summarizes the different formulations and dosages most widely studied, while highlighting reported outcomes and the occurrence of any adverse events.

Gastric peroral endoscopic myotomy versus botulinum toxin injection for the treatment of refractory gastroparesis: results of a double-blind randomized controlled study.

INTRODUCTION: Gastric peroral endoscopic myotomy (G-POEM) is a promising technique for treating refractory gastroparesis. We present the first double-blind randomized study comparing the clinical efficacy of G-POEM versus pyloric botulinum toxin injection (BTI). METHODS: This randomized study, conducted in two expert centers, enrolled patients with refractory gastroparesis, medically managed for >6 months and confirmed by gastric emptying scintigraphy (GES), into two groups, G-POEM versus BTI, with follow-up of 1 year. The primary end point was the 3-month clinical efficacy, defined as a >1-point decrease in the mean Gastroparesis Cardinal Symptom Index (GCSI) score. Secondary end points were: 1-year efficacy, GES evolution, adverse events, and quality of life. RESULTS: 40 patients (22 women; mean age 48.1 [SD 17.4]), with mean symptom duration of 5.8 (SD 5.7) years, were randomized. Etiologies included idiopathic (n=18), diabetes (n=11), postoperative (n=6), and mixed (n=4). G-POEM showed a higher 3-month clinical success than BTI (65% vs. 40%, respectively; P=0.10), along with non-significantly higher 1-year clinical success (60% vs. 40%, respectively) on intention-to-treat analysis. The GCSI decreased in both groups at 3 months and 1 year. Only three minor adverse events occurred in the G-POEM group. The GES improvement rate was 72% in the G-POEM group versus 50% in the BTI group (non-significant). CONCLUSION: G-POEM seems to have a higher clinically relevant success rate than BTI, but this was not statistically demonstrated. This study confirms the interest in treatments targeting the pylorus, either mechanically or chemically, for managing refractory gastroparesis.

Deep Brain Stimulation for Focal or Segmental Craniocervical Dystonia in Patients Who Have Failed Botulinum Neurotoxin Therapy-A Narrative Review of the Literature.

(1) Background: The first-line treatment for patients with focal or segmental dystonia with a craniocervical distribution is still the intramuscular injection of botulinum neurotoxin (BoNT). However, some patients experience primary or secondary treatment failure from this potential immunogenic therapy. Deep brain stimulation (DBS) may then be used as a backup strategy in this situation. (2) Methods: Here, we reviewed the current study literature to answer a specific question regarding the efficacy and safety of the use of DBS, particularly for cervical dystonia (CD) and Meige syndrome (MS) in patients with documented treatment failure under BoNT. (3) Results: There are only two studies with the highest level of evidence in this area. Despite this clear limitation, in the context of the narrowly defined research question of this paper, it is possible to report 161 patients with CD or MS who were included in studies that were able to show a statistically significant reduction in dystonic symptoms using DBS. Safety and tolerability data appeared adequate. However, much of the information is based on retrospective observations. (4) Conclusions: The evidence base in this area is in need of further scientific investigation. Most importantly, more randomized, controlled and double-blind trials are needed, possibly including a head-to-head comparison of DBS and BoNT.

A Narrative Literature Review of the Established Safety of Human Serum Albumin Use as a Stabilizer in Aesthetic Botulinum Toxin Formulations Compared to Alternatives.

Despite more than 80 years of use in a number of conditions, including in critically ill patients, comments have recently arisen regarding the safety and efficacy of human serum albumin (HSA) as a therapeutic product and stabilizer/excipient in botulinum neurotoxins. This review summarizes the literature on the safety of HSA. Beyond decades of safe use, the largest clinical dataset of HSA safety is a large meta-analysis of HSA supplier data, which found only an extremely remote risk of serious adverse events across millions of doses of therapeutic concentrations of HSA. There is a paucity of literature identifying HSA-specific adverse events when used as a stabilizer/excipient; however, studies of HSA-containing botulinum neurotoxins (BoNTs) suggest that adverse events are not related to HSA. Polysorbates, which are synthetically produced and not physiologically inert, are contained in pending or new-to-market BoNT formulations. In contrast to HSA, evidence exists to suggest that polysorbates (particularly PS20/PS80) can cause serious adverse events (e.g., hypersensitivity, anaphylaxis, and immunogenicity).

Effectiveness and safety of botulinum neurotoxin for treating dyssynergic defecation: A systematic review and meta-analysis.

Dyssynergic defecation (DD) is a common cause of chronic constipation. Owing to the lack of a comprehensive synthesis of available data on the effectiveness of botulinum neurotoxin (BoNT) for treating DD, we performed a systematic review and meta-analysis. We searched the PubMed, Embase, and Cochrane databases from inception to May 9, 2023. The outcomes comprise short-term and long-term symptom improvement, various anorectal function measurements, complications of fecal incontinence, and symptom improvement after repeated BoNT injections. A meta-analysis comparing BoNT injection with either surgery or biofeedback (BFB) therapy in treating DD was also conducted. Subgroup analysis and meta-regression were performed to identify possible moderator effects. We included five randomized controlled trials, seven prospective studies, and two retrospective observational studies. Short-term potential improvement in symptoms (event rate [ER], 66.4%; 95% CI, 0.513 to 0.783) was identified, but in the long-term (>12 months), this effect was decreased (ER, 38.2%; 95% CI, 0.267 to 0.511). Short-term improvements in objective anorectal physiologic parameters were also observed. Repeated BoNT injection was effective for patients with symptom recurrence. Subgroup analysis revealed enhanced long-term symptom improvement with high-dose BoNT, but this treatment also increased the risk of complications and recurrence compared with low doses. The effectiveness, complications, and recurrence of symptoms associated with BoNT injection and surgery did not differ significantly. BoNT injection significantly provided short-term symptom improvement but also heightened the risk of incontinence compared with BFB therapy. Our systematic review and meta-analysis indicated that BoNT could be beneficial for short-term symptom improvement in patients with DD, but this effect tended to decline 12 months after injection. Standardized BoNT intervention protocols remain warranted. Among the several treatments for DD, we concluded that BoNT injection is not inferior to other options considering its effectiveness in relieving symptoms, the associated complication development, and the risk of symptom recurrence.

Is Botulinum Toxin Effective in Treating Orofacial Neuropathic Pain Disorders? A Systematic Review.

BACKGROUND: The aim of this paper is to provide a systematic review of the literature regarding the clinical use of botulinum toxin (BTX) to treat various orofacial neuropathic pain disorders (NP). METHODS: A comprehensive literature search was conducted using Medline, Web of Science, and the Cochrane Library databases. Only randomized clinical trials (RCT) published between 2003 and the end of June 2023, investigating the use of BTX to treat NP, were selected. PICO guidelines were used to select and tabulate the articles. RESULTS: A total of 6 RCTs were selected. Five articles used BTX injections to treat classical trigeminal neuralgia, and one to treat post-herpetic neuralgia. A total of 795 patients received BTX injections. The selected studies utilised different doses and methods of injections and doses. All the selected studies concluded superiority of BTX injections over placebo for reducing pain levels, and 5 out 6 of them highlighted an improvement in the patient's quality of life. Most of the studies reported transient and mild side effects. CONCLUSION: There is evidence of the efficacy of BTX injections in orofacial pain management. However, improved study protocols are required to provide direction for the clinical use of BTX to treat various orofacial neuropathic pain disorders.

Longitudinal Assessment of Botulinum Toxin Treatment for Lateral Trunk Flexion and Pisa Syndrome in Parkinson's Disease: Real-life, Long-Term Study.

Lateral trunk flexion (LTF) and its severe form, called Pisa syndrome (PS), are highly invalidating axial postural abnormalities associated with Parkinson's disease (PD). Management strategies for LTF lack strong scientific evidence. We present a real-life, longitudinal study evaluating long-term efficacy of botulinum toxin (BoNT) injections in axial muscles to reduce LTF and PS in PD. A total of 13 PD patients with LTF > 5° received ultrasound- and electromyography-guided BoNT injections every 4 months. Seven untreated matched PD patients with LTF served as controls and their changes in posture after 18 months were compared with those of seven patients continuing BoNT over 12 months. 53.8% of patients continued the BoNT injections for at least 12 months. Various individual LTF responses were observed. Overall, BoNT-treated patients obtained a not statistically significant improvement of LTF of 17 ± 41% (p = 0.237). In comparison, the seven untreated PD patients suffered a deterioration in LTF over 12 months by 36 ± 45% (p = 0.116), showing a significantly different trajectory of posture change (p = 0.026). In conclusion, repeated BoNT injections in axial muscles showed varying effects in managing PD-associated LTF, suggesting that: (a) a relevant number of patients with LTF can benefit from BoNT; (b) long-term treatment could prevent LTF worsening; (c) an instrumented, personalized approach is important; and (d) there is a need for prospective, long-term studies.

Beyond Wrinkles: A Comprehensive Review of the Uses of Botulinum Toxin.

BACKGROUND: Botulinum neurotoxin (BoNT) exhibits inhibitory effects on the neuromuscular junction, and its use is well established in cosmetic dermatology. Our review aims to analyze the evidence for its use in the treatment of various dermatological, neurological, gastroenterological, ophthalmological, otorhinolaryngological, dental, urological, gynecological, and cardiovascular disorders. METHODS: A systematic review of the literature was performed for studies published between 2012 and 2022 that discussed the therapeutic use of BoNT in human participants. A total of 58 studies were selected for inclusion in this review. RESULTS: We discovered a large range of therapeutic applications of BoNT toxin beyond aesthetic and US Food and Drug Administration (FDA)-approved non-aesthetic uses. CONCLUSIONS: BoNT is a powerful neurotoxin that has varied FDA-approved indications and has been studied in a wide range of therapeutic applications. Further investigation through higher power studies is needed to assess the potential of BoNT and expand its versatility across other medical specialties. J Drugs Dermatol. 2023;22(9): doi:10.36849/JDD.7243e.

A large travel-associated outbreak of iatrogenic botulism in four European countries following intragastric botulinum neurotoxin injections for weight reduction, Türkiye, February to March 2023.

In March 2023, 34 associated cases of iatrogenic botulism were detected in Germany (30 cases), Switzerland (two cases), Austria (one case), and France (one case). An alert was rapidly disseminated via European Union networks and communication platforms (Food- and Waterborne Diseases and Zoonoses Network, EpiPulse, Early Warning and Response System) and the International Health Regulation mechanism; the outbreak was investigated in a European collaboration. We traced sources of the botulism outbreak to treatment of weight loss in Türkiye, involving intragastric injections of botulinum neurotoxin. Cases were traced using a list of patients who had received this treatment. Laboratory investigations of the first 12 German cases confirmed nine cases. The application of innovative and highly sensitive endopeptidase assays was necessary to detect minute traces of botulinum neurotoxin in patient sera. The botulism notification requirement for physicians was essential to detect this outbreak in Germany. The surveillance case definition of botulism should be revisited and inclusion of cases of iatrogenic botulism should be considered as these cases might lack standard laboratory confirmation yet warrant public health action. Any potential risks associated with the use of botulinum neurotoxins in medical procedures need to be carefully balanced with the expected benefits of the procedure.

Effects of the periocular botulinum toxin on the ocular surface and anterior chamber: a prospective study in patients with hemifacial spasm and blepharospasm.

PURPOSE: To analyze using Pentacam®, the corneal and anterior chamber changes following periocular botulinum toxin injection in patients with facial dystonia. METHODS: Prospective study that included patients with facial dystonia that were going to receive a periocular botulinum toxin injection for the first time or six months or more after the previous injection. A Pentacam® examination was carried out in all patients before and 4 weeks after the injection. RESULTS: Thirty-one eyes were included. Twenty-two had a diagnosis of blepharospasm and nine of hemifacial spasm. Analysis of corneal and anterior chamber parameters revealed a significant decrease in iridocorneal angle after botulinum toxin injection (from 35 ± 10º to 33.8 ± 9.7º, p = 0.022). No other corneal or anterior chamber parameters changed significantly after the injection. CONCLUSIONS: Periocular botulinum toxin injection causes narrowing of the iridocorneal angle.

Systematic Review on Botulinum Toxin Injections as Diagnostic or Therapeutic Tool in Thoracic Outlet Syndrome.

BACKGROUND: The optimal diagnostic and treatment algorithm for patients with suspected thoracic outlet syndrome (TOS) remains challenging. Botulinum toxin (BTX) muscle injections have been suggested to shrink muscles in the thoracic outlet reducing neurovascular compression. This systematic review evaluates the diagnostic and therapeutic value of BTX injections in TOS. METHODS: A systematic review of studies reporting BTX as a diagnostic or therapeutic tool in TOS (or pectoralis minor syndrome as TOS subtype) was conducted in PubMed, Embase, and CENTRAL databases on May 26, 2022. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement was followed. Primary end point was symptom reduction after primary procedure. Secondary end points were symptom reduction after repeated procedures, the degree of symptom reduction, complications, and duration of clinical effect. RESULTS: Eight studies (1 randomized controlled trial [RCT], 1 prospective cohort study, and 6 retrospective cohort studies) were included reporting 716 procedures in at least 497 patients (at minimum 350 primary and 25 repeated procedures, residual unclear) diagnosed with presumably only neurogenic TOS. Except for the RCT, the methodological quality was fair to poor. All studies were designed on an intention to treat basis, one also investigated BTX as a diagnostic tool to differentiate pectoralis minor syndrome from costoclavicular compression. Reduction of symptoms was reported in 46-63% of primary procedures; no significant difference was found in the RCT. The effect of repeated procedures could not be determined. Degree of symptom reduction was reported by up to 30-42% on the Short-form McGill Pain scale and up to 40 mm on a visual analog scale. Complication rates varied among studies, no major complications were reported. Symptom relief ranged from 1 to 6 months. CONCLUSIONS: Based on limited quality evidence, BTX may provide short-lasting symptom relief in some neurogenic TOS patients but remains overall undecided. The role of BTX for treatment of vascular TOS and as a diagnostic tool in TOS is currently unexploited.

Comparison of Oropharyngeal Dysphagia Before and After Botulinum Toxin Injection in Cervical Dystonia.

Cervical dystonia (CD) is the most common form of focal dystonia with Botulinum neurotoxin (BoNT) being a frequent method of treatment. Dysphagia is a common side effect of BoNT treatment for CD. Instrumental evaluation of swallowing in CD using standardized scoring for the videofluoroscopic swallowing study (VFSS) and validated and reliable patient-reported outcomes measures is lacking in the literature. (1) to determine if BoNT injections change instrumental findings of swallowing function using the Modified Barium Swallow Impairment Profile (MBSImP) in individuals with CD; (2) to determine if BoNT injections change self-perception of the psychosocial handicapping effects of dysphagia in individuals with CD, using the Dysphagia Handicap Index (DHI); (3) to determine the effect of BoNT dosage on instrumental swallowing evaluation and self-reported swallowing outcomes measures. 18 subjects with CD completed a VFSS and the DHI before and after BoNT injection. There was a significant increase in pharyngeal residue for pudding consistency after BoNT injection, p = 0.015. There were significant positive associations between BoNT dosage and self-perception of the physical attributes of the handicapping effect of dysphagia, the grand total score and patient self-reported severity of dysphagia on the DHI; p = 0.022; p = 0.037; p = 0.035 respectively. There were several significant associations between changes in MBSImP scores and BoNT dose. Pharyngeal efficiency of swallowing may be affected by BoNT for thicker consistencies. Individuals with CD perceive greater physical handicapping effects of dysphagia with increased amounts of BoNT units and have greater self-perceptions of dysphagia severity with increased amounts of BoNT units.

Botulinum toxin injection in vulva and vagina. Evidence from a literature systematic review.

INTRODUCTION: Botulinum toxin (BoNT) administration has been proposed in the gynecologic field for pelvic, vulvar and vaginal disorders. On this regard, we aimed assessing the therapeutic effectiveness and safety of BoNT usage in the treatment of vaginal, vulvar and pelvic pain disorders. METHODS: We searched for all the original articles without date restriction until 31.12.2021. We included all the original articles which administered botulinum toxin in the vulva or vagina of women suffering from vaginismus, dyspareunia, and chronic pelvic pain. Only English language studies and those performed in humans were eligible. We excluded all case reports and pilot study from the qualitative analysis, although we accurately evaluated them. 22 original studies were finally included in the systematic review. RESULTS: Botulinum toxin injection was found to be effective in improving vulvar and vaginal dyspareunia, vaginismus, and chronic pelvic pain. No irreversible side effects were detected. Major side effects reported were transient urinary or fecal incontinence, constipation and rectal pain. The risk of bias assessment proved original articles to be of medium quality. No metanalysis could have been performed since lack of congruency in the definition of pathology and methods of botulinum toxin administration. CONCLUSION: Data extraction pointed out different endpoints and different methods of analysis. Studies focus on different types of participants and use various techniques and timing. According to the best evidence available, different techniques provide evidence about positive outcomes, with the need for a standardized protocol.

Botulismo alimentar: relato de caso de uma doença rara, grave e de relevância para a saúde pública / Foodborne botulism: case report of a rare, serious disease of public health relevance

Este resumo apresenta o relato de um caso de Botulismo ocorrido em maio de 2021 no Hospital do Servidor Público Municipal (HSPM) em São Paulo. O objetivo principal é sensibilizar os profissionais de saúde para considerar o Botulismo como uma possível causa de síndrome neuroparalítica aguda, apesar de sua raridade. Destaca-se a importância do diagnóstico precoce e do tratamento com antitoxina, juntamente com cuidados intensivos, para reduzir a mortalidade. O estudo é observacional e descritivo, relatando o caso de uma paciente hospitalizada com Botulismo de origem alimentar entre maio e agosto de 2021. Diante de uma síndrome neuroparalítica aguda, a suspeita de Botulismo e uma revisão da epidemiologia da doença são cruciais. Destaca-se a importância da antitoxina e dos cuidados intensivos no tratamento para reduzir a mortalidade. Complicações pós-infecção, como sequelas motoras, são comuns em pacientes de Botulismo, tornando essencial uma abordagem multidisciplinar de reabilitação física para uma recuperação eficaz. A Vigilância Epidemiológica e Sanitária desempenham um papel vital na prevenção e controle do Botulismo, incluindo a coleta e transporte oportunos de amostras, busca ativa de casos suspeitos e orientação à população sobre medidas preventivas. A qualidade dos dados notificados é fundamental para a eficácia dessas ações. Em vista da alta letalidade do Botulismo, destaca-se a importância de alertar os profissionais de saúde para identificar casos suspeitos, bem como treiná-los na integração com as unidades de Vigilância Sanitária e Epidemiológica. Isso permite uma identificação precoce e tratamento oportuno de casos suspeitos, contribuindo para a saúde pública. Palavras-chave: Botulismo. Neurotoxina botulínica. Intoxicação alimentar.

Quality of Life in Female Patients with Overactive Bladder after Botulinum Toxin Treatment.

BACKGROUND: Manifestations of OAB can considerably diminish the quality of life. Botulinum toxin has emerged as a valuable treatment option in diseases whose symptoms cannot be controlled adequately with other available therapies. The aim of the present study was to compare the subjective quality of life of patients with OAB before the injection of botulinum toxin and three and six months after the intervention. METHODS: This study was based on a diagnostic survey with three validated questionnaires, ICIQ-OAB, ICIQ-OABqol, and ICIQ-LUTSqol, and an additional questionnaire developed by the authors to collect sociodemographic characteristics and selected medical data. RESULTS: This study demonstrated significant differences between pre-treatment scores and those at three and six months post injection. At three and six months after the intervention, mean scores for all three instruments (ICIQ-OAB, ICIQ-OABqol, ICIQ-LUTSqol) were significantly lower than the respective pre-treatment values, implying a significant attenuation of OAB symptoms and their lower impact on the quality of life. However, the severity of OAB symptoms and their impact on the quality of life at six months post intervention were significantly higher than at three months, except for the social interaction domain. CONCLUSIONS: Botulinum toxin is an effective treatment for OAB.

Epidemiology and risk factors for notifiable Clostridium botulinum infections in Taiwan from 2003 to 2020.

Botulinum toxin is produced by Clostridium botulinum, a gram-positive anaerobic bacterium. This study aimed to examine the epidemiological characteristics, including sex, age, season in which infection occurred, place of residence, and epidemiological trends, of confirmed botulism cases in Taiwan from 2003 to 2020. This study examined the annual summary data on reported botulism in Taiwan' s Center for Disease Control from 2003 to 2020 available to the public on the internet. We found that there were 50 confirmed domestic cases of botulism. The incidence of botulism ranged from 0 to 0.48 per 1000,000 from 2003 to 2020 and peaked in 2008 and 2010. During the 18-year investigation period in which 6-year intervals were used, the study results showed a decreasing trend (2003-2008, 2009-14, and 2015-2020, had 22, 19, 9 cases each). In terms of patients' gender, age, and place of residence, most of the patients were females (56%), were aged ≥ 50 years (48%), and resided in Taipei and northern Taiwan (44%). The number of botulism cases in Taiwan from 2012 to 2020 compared with other years (from 2003 to 2011) found that there were significant differences among patients within an age group of <20 years (P = .003, odds ratio = 18.500, and 95% confidence interval = 3.287-104.111), and there were significant differences among patients whose place of residence was Taipei metropolitan area (P = .025, odds ratio = 5.667, and 95% confidence interval = 1.248-25.734). During 2003 to 2009, there was no case of botulism among those aged <20 years. Over the last 10 years, botulism in children showed an increasing trend. A total of 9 children were found to have botulism during 2010 to 2020; most of these children were male (66.7%) and were infected during spring and summer (66.7%). This study is the first to report the number of confirmed domestic cases with botulism from surveillance data from Taiwan's Center for Disease Control during 2003 to 2020. This study also found that the place of residence and age were associated with an increased risk of botulism in Taiwan. This information may be useful for policymakers and clinical experts to direct prevention- and control-based activities regarding botulism that result in the most severe illness and the greatest burden on Taiwanese.

Botulinum Toxin Therapy for Spasmodic Dysphonia in Japan: The History and an Update.

Spasmodic dysphonia (SD) is a rare neurological disorder that impairs phonatory function by triggering involuntary and intermittent contractions of the intrinsic laryngeal muscles. SD is classified into three types: adductor SD (AdSD), abductor SD (AbSD), and mixed SD. Of these, AdSD accounts for 90-95% of disease; younger females are predominantly affected. Botulinum toxin injection into the laryngeal muscles is safe, minimally invasive, and very effective. Here, we review the history of clinical research for SD conducted in Japan. The first use of botulinum toxin injection therapy to treat SD in Japan was by Kobayashi et al. in 1989. The group developed an objective mora (syllable) method to evaluate SD severity. Recently, we conducted a placebo-controlled, randomized, double-blinded clinical trial of botulinum toxin therapy for AdSD and an open-label trial for AbSD to obtain the approval of such therapy by the Japanese medical insurance system. The mora method revealed significant voice improvement and the evidence was of high quality. Additionally, a clinical trial of type 2 thyroplasty using titanium bridges confirmed the efficacy and safety of such therapy. These studies broadened the SD treatment options and have significantly benefited patients.

Exposure-Response Modeling and Simulation to Support Human Dosing of Botulism Antitoxin Heptavalent Product.

Botulism antitoxin heptavalent (A, B, C, D, E, F, and G - Equine; BAT) product is a sterile solution of F(ab')2 and F(ab')2 -related antibody fragments prepared from plasma obtained from horses that have been immunized with a specific serotype of botulinum toxoid and toxin. BAT product is indicated for the treatment of symptomatic botulism following documented or suspected exposure to botulinum neurotoxin serotypes A to G in adults and pediatric patients. Pharmacokinetic and exposure-response models were used to explore the relationship between BAT product exposure and the probability of survival, and the occurrence of relevant moderate clinical signs observed during the preclinical development of BAT product to justify the clinical dose. The predicted probability of survival in humans for all serotypes of botulinum neurotoxin was more than 95.9% following intravenous administration of one vial of BAT product. Furthermore, this BAT product dose is expected to result in significant protection against clinical signs in human adults for all botulinum neurotoxin serotypes. Our exposure response model indicates that we have sufficient antitoxin levels to give full protection at various theoretical exposure levels and, based on neutralization capacity/potency of one dose of BAT product, it is expected to exceed the amount of circulating botulinum neurotoxin.

Botulinum Toxin in Hidradenitis Suppurativa: A Systematic Review.

BACKGROUND: Hidradenitis suppurativa disproportionately affects women, minorities, and skin of color. Botulinum toxin is a potential therapy; however, literature regarding its utility is sparse. OBJECTIVE: We analyzed evidence surrounding botulinum toxin in the treatment of hidradenitis suppurativa. METHODS: We conducted a database search of PubMed, Embase, and Cochrane library for studies addressing botulinum toxin therapy for hidradenitis suppurativa through June 10, 2020. Review articles, meta-analyses, and studies without published results were excluded. RESULTS: Seven studies met criteria for inclusion and review. Botulinum toxin administration resulted in either clinical improvement or improved quality of life in 96.8% (n = 30/31) of patients. Level of evidence was moderate. LIMITATIONS: Results are limited by the quantity and evidence level of reviewed studies. CONCLUSION: Botulinum toxin is a safe and potentially effective alternative for hidradenitis suppurativa patients resistant to standard of care therapies. Dermatologists can address this health disparity by strengthening recommendations with high-quality investigations regarding its therapeutic potential. J Drugs Dermatol. 2022;21(4):408-412. doi:10.36849/JDD.5747.

A Retrospective and Anatomical Study Describing the Injection of Botulinum Neurotoxins in the Depressor Anguli Oris.

SUMMARY: The depressor anguli oris acts to lower the lateral corners of the mouth and can cause an individual to appear sad or angry and contribute to the development of the labiomental folds. Many patients can benefit from the injection of small amounts of botulinum neurotoxin into the depressor anguli oris to enable the lip elevators to reposition the corners of the mouth. Although effective, the procedure is off-label, and the proximity of the depressor anguli oris to the depressor labii inferioris, particularly inferiorly, can lead to inadvertent treatment of the latter, resulting in lip asymmetry. The authors have taken a threefold approach to establish a depressor anguli oris injection technique that provides optimal aesthetic outcomes with a low incidence of adverse events. This involved, first, reviewing the limited existing literature for studies discussing depressor anguli oris anatomy and botulinum neurotoxin treatment technique; second, supplementing information from the published literature with information from cadaver dissections to demonstrate the relationship between the depressor anguli oris and surrounding anatomical structures; and third, performing a retrospective chart review of 275 patients treated with the authors' three-point injection technique. Combining data from published studies, cadaver dissections, and clinical experience, the authors demonstrate that a three-point technique performed in the upper half of the depressor anguli oris is associated with good clinical outcome and avoids common side effects related to injection or spread of neurotoxin to adjacent muscles. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.