Efficacy and Safety of Low-Dose Intravesical OnabotulinumtoxinA Injections in Female Patients With Detrusor Overactivity With Detrusor Underactivity.

PURPOSE: We assessed the effectiveness and safety of using intravesical onabotulinumtoxinA (onabotA; BOTOX) injection with a low dose (75 units) for treating urinary storage symptoms in patients with detrusor overactivity with detrusor underactivity (DODU) compared to using the standard 100 units of onabotA in patients with overactive bladder (OAB). METHODS: This ambidirectional study included 121 female patients who received intravesical onabotA injections at our hospitals. A total of 87 patients with OAB and 34 patients with DODU were reviewed using a 3-day voiding diary, uroflowmetry, and questionnaires including the International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score, and Patient Perception of Bladder Condition. Patients were evaluated at baseline, within 2 weeks of treatment, and beyond 3 months after treatment. RESULTS: Questionnaire scores of the DODU group demonstrated significant improvement in the short term, with a subsequent decline, but an overall improvement compared to baseline in the long term. Notably, the DODU group exhibited enhanced IPSS voiding scores after the treatment. In the OAB group, most questionnaire scores, excluding the IPSS voiding score, showed significant posttreatment improvement, which was sustained to some extent in the long term. Voiding diary parameters related to storage symptoms were enhanced in both groups. The maximum and mean flow rates decreased in the OAB group but increased in the DODU group, particularly in the short term (P=0.000). The postvoid residual volume increased in both groups after posttreatment, with a mitigated change in the long term. Safety assessments revealed manageable adverse events in both groups with comparable frequencies. CONCLUSION: Low-dose intravesical onabotA for DODU demonstrated a relatively shorter duration of efficacy than OAB. Nonetheless, the treatment improved both storage and voiding symptoms in patients with DODU without significant adverse effects.

Retrograde Cricopharyngeus Dysfunction, a New Motility Disorder: Single Center Case Series and Treatment Results.

Background/Aims: Retrograde cricopharyngeus dysfunction (R-CPD) is a new clinical entity characterized by inability to belch and associated symptoms of loud gurgling noises, chest and/or abdominal pressure, abdominal bloating, and excessive flatulence. R-CPD can be treated with botulinum toxin (BT) injection in the upper esophageal sphincter. We hereby report patient demographics, symptomatology, and treatment results of a series of consecutive patients who presented at our center. Methods: Data on 50 consecutive patients presenting with R-CPD were prospectively collected using a standardized questionnaire prior to, 1 month after treatment and at the end of follow-up. All patients were diagnosed using a set of clinical symptoms. Results: Fifty patients (26 females) were included, median age was 27.5 years (range, 17-65). Median body mass index was 22.7 kg/m2 (range, 16.6-37.5). Inability to belch was present in all patients, > 90% of patients experienced gurgling noises and abdominal/chest discomfort as result of their condition. One month after injection of BT, 40.8% of patients experienced complete relief of symptoms, 24.5% good symptom improvement, 24.5% some symptom improvement and 10.2% no improvement. At median follow-up of 29 months (range, 3-50) post-treatment, 51.3% (n = 20/39) of patients reported persistent complete relief of symptoms, 12.8% good improvement of symptoms (n = 5/39), in 15.4% some improvement (6/39) and 20.5% loss of or no response (n = 8/39). Only minor and transient side effects were reported. Conclusions: Our case series of 50 patients with R-CPD shows very good short-term and good long-term improvement of symptoms after injection of BT. These results are in line with previous studies.

Cosmiatria: Uma análise do mercado brasileiro / Cosmiatry: An analysis of the Brazilian market

Introdução: O mercado de procedimento estéticos cresce exponencialmente no Brasil. Tal crescimento tem despertado o interesse de várias categorias profissionais. A decisão de praticar no setor deve considerar as oportunidades de mercado da localidade na qual se pretende atuar. Entretanto, a área carece de análises comparativas documentando prováveis diferenças regionais no país. O objetivo do estudo é descrever as diferenças de mercado em procedimentos estéticos entre os estados e regiões brasileiras. Um índice de potencial consumo de cosmiatria (IPCC) é calculado para tal análise comparativa. Método: Estudo transversal envolvendo prestadores de procedimentos estéticos não cirúrgicos no Brasil. Buscas no Google®-Google Maps® foram conduzidas usando termoschave e entrevistas telefônicas realizadas para obter informações sobre categorias profissionais, tipo de provedores e serviços oferecidos. Valores preditivos positivos foram obtidos para todas as estratégias de busca e usados para estimar o número total de provedores. O tamanho da população e a renda per capita foram considerados para o cálculo dos IPCCs para os estados brasileiros. Resultados: São Paulo, Minas Gerais e Rio de Janeiro apresentaram os maiores IPCCs, sendo 524, 210 e 180, respectivamente. Roraima teve um IPCC de 14, o mais baixo do país. A Região Sudeste apresentou, em média, o maior IPCC (242) entre todas as regiões brasileiras. Conclusão: Considerando o tamanho da população e a renda, a Região Sudeste apresenta as maiores oportunidades de mercado em procedimentos estéticos não cirúrgicos no Brasil. Nossos achados podem ser de interesse para profissionais de saúde e investidores que atuam ou pretendem atuar no setor.

Introduction: The aesthetic procedure market is growing exponentially in Brazil. This growth has aroused the interest of several professional categories. The decision to practice in the sector must consider the market opportunities in the location in which you intend to operate. However, the area lacks comparative analyses documenting probable regional differences in the country. The objective of the study is to describe market differences in aesthetic procedures between Brazilian states and regions. An index of potential cosmetic consumption (IPCC) is calculated for such a comparative analysis. Method: Cross-sectional study involving providers of nonsurgical aesthetic procedures in Brazil. Searches on Google Maps® were conducted using key terms, and telephone interviews were conducted to obtain information on professional categories, types of providers, and services offered. Positive predictive values were obtained for all search strategies and used to estimate the total number of providers. Population size and per capita income were considered to calculate the IPCCs for Brazilian states. Results: São Paulo, Minas Gerais, and Rio de Janeiro presented the highest IPCCs, being 524, 210, and 180, respectively. Roraima had an IPCC of 14, the lowest in the country. The Southeast Region presented, on average, the highest IPCC (242) among all Brazilian regions. Conclusion: Considering population size and income, the Southeast Region presents the greatest market opportunities for nonsurgical aesthetic procedures in Brazil. Our findings may be of interest to healthcare professionals and investors who work or intend to work in the sector.

Parry-Romberg syndrome: A case report and literature review.

Parry-Romberg syndrome (PRS) is a rare neurocutaneous and craniofacial disorder characterized by progressive hemifacial wasting and atrophy that predominantly affects children and young adults, with an estimated prevalence of 1 in 700,000 individuals. Despite its rarity, PRS poses significant challenges for patients, their families, and healthcare providers due to its unpredictable course and potential functional and aesthetic impairments. The main aim is to provide a comprehensive overview of PRS, encompassing its clinical features, pathogenesis, and management techniques. We present a case of PRS in a 9-year-old female with pronounced facial asymmetry, with marked wasting and atrophy involving the entire right side of the face. CT scan revealed right sided hypoplasia of maxilla, mandible, and zygomatic arch with enophthalmos of right eye. MRI showed right temporalis, medial and lateral pterygoid, masseter, risorius, buccinator, zygomaticus major and minor, levator labii superioris, levatorangulioris and orbicularis oris muscles atrophy. The clinical presentation of PRS typically involves progressive facial atrophy, predominantly affecting the subcutaneous tissues, muscles and bones. Patients may experience various symptoms as the condition advances, including facial asymmetry, hemifacial pain, dental and ocular abnormalities and neurological manifestations. The exact etiology of PRS remains unknown, although autoimmune, genetic and vascular factors are likely contributors. Treatment of PRS needs a multidisciplinary approach involving dermatologists, plastic surgeons, neurologists, ophthalmologists, and dental specialists. Treatment options aim to alleviate symptoms, improve function and address cosmetic concerns. Surgical interventions such as autologous fat grafting, facial reconstructive procedures and orthognathic surgery have restored facial symmetry and function. Additionally, nonsurgical modalities, including botulinum toxin injections, prosthetic devices and dental interventions, may offer symptomatic relief and enhance overall quality of life.

Real-world differences in dosing and clinical utilization of OnabotulinumtoxinA and AbobotulinumtoxinA in the treatment of upper limb spasticity.

According to prescribing information, potency units are not interchangeable between botulinum toxin A products. This exploratory study compared real-world dosing and utilization of onabotulinumtoxinA and abobotulinumtoxinA in adults with upper limb spasticity. In this retrospective study, 101 clinicians provided chart data via online surveys for 215 US post-stroke patients treated for upper limb spasticity with ≥3 onabotulinumtoxinA or abobotulinumtoxinA doses (phase 1: 9/18/2020-12/10/2020; phase 2: 9/30/2021-12/7/2021). Most participating clinicians were physicians (70.3%) specializing in neurology (71.3%) or physiatry (20.8%). In the onabotulinumtoxinA (n = 107) and abobotulinumtoxinA (n = 108) groups, ∼75% of patients had moderate-to-severe spasticity. A range of onabotulinumtoxinA:abobotulinumtoxinA dose ratios (1:2.2 [95% CI: 1.8, 2.6] to 1:4.1 [95% CI: 3.0, 6.0]) was observed across muscles. For the most recent dose, mean number of muscles injected was greater for onabotulinumtoxinA (4.3) versus abobotulinumtoxinA (3.1; P = 0.0003). For onabotulinumtoxinA versus abobotulinumtoxinA, the proportion of injections was 81.3% versus 63.9% (P = 0.0067) in forearm muscles and 23.4% versus 3.7% (P = 0.0001) in hand muscles. Mean injection intervals were similar (onabotulinumtoxinA: 102.0 days; abobotulinumtoxinA: 99.1 days). Differences in real-world dosing and utilization of onabotulinumtoxinA and abobotulinumtoxinA for upper limb spasticity were observed. There was no standard dose-conversion ratio, consistent with each product's prescribing information.

Outcomes Following Intrasphincteric Injection of Botulinum Toxin for Treatment of Anal Fissures.

Background Intrasphincteric injection of botulinum toxin is an alternative treatment for anal fissures, which may present less risk of fecal incontinence than more invasive procedures, such as lateral internal sphincterotomy. The aim is to compare cure and complication rates between these two treatments. Methods We conducted a retrospective audit of patients who underwent treatment of anal fissures with intrasphincteric botulinum toxin or lateral internal sphincterotomy from 2016 to 2020 at the Colorectal Surgery Unit of Monash Health, Melbourne, Australia, excluding those who had previously had either procedure. Results Fifty-one patients received intrasphincteric botulinum toxin, and 40 patients underwent lateral internal sphincterotomy. Most patients in the botulinum group had a total dose of either 80 (53%; n=27) or 100 units (37%; n=19) and had the dose administered bilaterally at the 3 o'clock and 9 o'clock positions (n=41; 80%). Thirty-one patients in the botulinum group (61%) had complete resolution of symptoms, with a mean time to cure of two months, compared to 36 patients (90%) in the sphincterotomy group with a mean time to cure of 1.5 months. In most cases, postoperative incontinence was transient, although one patient in the botulinum group had persistent incontinence of flatus, and two patients in the sphincterotomy group had persistent fecal incontinence. Conclusion Intrasphincteric botulinum injection is an effective, less-invasive alternative to sphincterotomy for the treatment of anal fissures, with incontinence usually temporary when it occurs. Further research is needed to optimize the dose and location of injection and guide future recommendations.

Adverse effect of botulinum toxin-A injections on mandibular bone: A systematic review and meta-analysis.

INTRODUCTION: Botulinum toxin-A (BTX) is a potent neurotoxin that is emerging in the scope of dental practice for its ability to temporarily paralyse musculature and reduce hyperfunction. This may be desirable in diseases/disorders associated with hyperactive muscles such as the muscles of mastication, most implicated in painful temporomandibular disorders (TMDs). The use of BTX extends beyond its indications with off-label use in TMD's and other conditions, while potential adverse effects remain understudied. BTX is well-established hindlimb paralysis model in animals leading to significant bone loss with underlying mechanisms remaining unclear. The objective of this study is to systematically review the literature for articles investigating changes in mandibular bone following BTX injections and meta-analyse available data on reported bone outcomes. METHODS: Comprehensive search of Medline, Embase and Web of Science retrieved 934 articles. Following the screening process, 36 articles in animals and humans were included for quantitative synthesis. Articles in human individuals (6) and three different animal species (14) presented mandibular bone outcomes that were included in the meta-analysis. RESULTS: The masseter and temporalis muscles were frequently injected across all species. In humans, we observe a decrease of about 6% in cortical thickness of mandibular regions following BTX injection with no evident changes in either volume or density of bone structures. In animals, bone loss in the condylar region is significantly high in both cortical and trabecular compartments. DISCUSSION: Our analysis supports the concept of BTX-induced bone-loss model in animal mandibles. Further, bone loss might be confined to the cortical compartments in humans. Most studies did not address the reality of repeated injections and excessive dosing, which occur due to the reversible action of BTX. More rigorous trials are needed to draw a full picture of potential long-term adverse effects on bone.

Facial phantom model: a low-cost and safe tool for teaching botulinum toxin application in neurology residencies / Modelo de manequim facial: uma ferramenta segura e de baixo custo para o ensino da aplicação de toxina botulínica nas residências em neurologia

Abstract Background The application of botulinum toxin (BoNT) in the treatment of blepharospasm and hemifacial spasm (HS) is a well-established practice. However, neurology residency programs often rely on real patients for training, which has limitations in terms of patient availability and skill acquisition. Objective Assess the efficacy of a new facial phantom model for acquiring motor skills in BoNT application. Methods An anthropomorphic facial phantom model was developed in collaboration with a medical training simulator start-up. A group of seven neurologists and one ophthalmologist with expertise in BoNT application evaluated the model using an adapted learning object review instrument (LORI). The instrument assessed aspects such as: content quality, alignment of learning objectives, feedback and adaptation, motivation, presentation design, and accessibility. Results The facial phantom model received high scores in the LORI evaluation, with the highest ratings given to alignment with learning objectives and motivation. The model also scored well in terms of accessibility, content quality, and presentation design. However, feedback and adaptation received a lower score due to the static nature of the model. Conclusion The facial phantom model shows promise as a valuable tool for teaching and developing competence in BoNT application for HS and blepharospasm. The model reduces the reliance on real patients for training, providing a broader and safer learning experience for neurology residents. It also provides a realistic learning experience and offers portability, cost-effectiveness, and ease of manufacturing for use in various medical training scenarios. It is an effective and accessible tool for teaching BoNT application.

Resumo Antecedentes A aplicação de toxina botulínica (TxB) no tratamento do blefaroespasmo e do espasmo hemifacial (EH) é uma prática bem estabelecida. No entanto, os programas de residência em neurologia frequentemente dependem de pacientes reais para treinamento, o que apresenta limitações em termos de disponibilidade de pacientes e aquisição de habilidades. Objetivo Avaliar a eficácia de um novo modelo de manequim facial para aquisição de habilidades motoras na aplicação de TxB. Métodos Foi desenvolvido um modelo antropomórfico de manequim facial em coloboração com uma empresa de simuladores de treinamento médico. Um grupo constituído por sete neurologistas e um oftalmologista com experiência em aplicação de TxB avaliou o modelo utilizando um instrumento adaptado de revisão de objeto de aprendizagem (LORI). O instrumento analisou aspectos como: qualidade do conteúdo, alinhamento dos objetivos de aprendizagem, feedback e adaptação, motivação, concepção da apresentação e acessibilidade. Resultados O modelo de manequim facial obteve pontuações altas na avaliação do LORI com os maiores escores em alinhamento com os objetivos de aprendizagem e motivação. O modelo também obteve boas pontuações em termos de acessibilidade, qualidade do conteúdo e concepção da apresentação. No entanto, o item feedback e adaptação recebeu uma pontuação média mais baixa, devido à natureza estática. Conclusão O modelo manequim facial mostra-se promissor como uma EH e blefaroespasmo. O modelo reduz a dependência de pacientes reais para treinamento portátil, de baixo custo e de fácil fabricação para uso em diversos cenários de treinamento, proporcionando uma experiência de aprendizagem mais ampla e segura para residentes de neurologia. Além disso, fornece uma experiência de aprendizagem realista e oferece portabilidade, economia e facilidade de fabricação para uso em vários cenários de treinamento médico. É uma ferramenta eficaz e acessível para o ensino da aplicação de TxB.

The effect of botulinum toxin A in children with non-neurogenic therapy-refractory dysfunctional voiding - A systematic review.

INTRODUCTION: Dysfunctional voiding (DV) is a habitual voiding disorder caused by involuntary contraction or non-relaxation of the external urethral sphincter (EUS) during voiding. This contraction causes high post-void residuals (PVR), urinary incontinence and urinary tract infections (UTIs). Various treatments for DV are available, but some children do not respond. Intersphincteric botulinum toxin-A (BTX-A) may be a possible treatment for therapy-refractory children with DV. OBJECTIVE: The aim of this systematic review is to summarize the effects and safety of intersphincteric BTX-A as a treatment for therapy-refractory DV in children. METHODS: A systematic search in Embase, MEDLINE, Cochrane, and Web of Science databases was performed. Studies reporting on the usage of intersphincteric BTX-A as a treatment for DV in children were included. Data on PVR, maximum flow rate (Qmax), repeat injections and complications were extracted. RESULTS: From a total of 277 articles, five cohort studies were identified, reporting on 78 children with DV of whom 53 were female (68 %) and 25 were male (32 %). Sample sizes ranged from ten to twenty patients. Mean or median age at the time of intervention ranged from 8 to 10.5 years. Meta-analysis could not be performed due to lack of data. The narrative synthesis approach was therefore used to summarize the results. All studies showed significant decrease in PVR after BTX-A injection. Three studies showed a 33-69 % improvement on incontinence after BTX-A injection. Less UTIs were reported after treatment. A temporary increase in incontinence, UTIs and transitory numbness to the gluteus muscle were reported as side-effects. CONCLUSIONS: BTX-A could be a safe and effective treatment option for therapy-refractory DV in children by reducing PVR, UTIs and incontinence. Hereby, the synergistic effect of BTX-A and urotherapy should be emphasized in future management. Furthermore, this study identified gaps in current knowledge that are of interest for future research.

Effect of botulinum toxin type A on muscular temporomandibular disorder: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Botulinum toxin type A (BTX-A) is increasingly used to manage painful temporomandibular disorders (TMD). However, the effect of BTX-A on muscular TMD remains unclear. OBJECTIVE: To assess the efficacy, safety and optimal dose of BTX-A for treating TMD. METHODS: We conducted systematic literature searches in MEDLINE, Embase, Web of Science, ClinicalTrials.gov and Cochrane Library until March 2023. We extracted data from randomized controlled trials (RCTs) that evaluated the efficacy and safety of BTX-A in treating muscular TMD. We performed a meta-analysis using a random-effects model. RESULTS: Fifteen RCTs involving 504 participants met the inclusion criteria. BTX-A was significantly more effective than placebo in reducing pain intensity, as measured on a 0-10 scale, at 1 month (MD [95% CI] = -1.92 [-2.87, -0.98], p < .0001) and 6 months (MD [95% CI] -2.08, [-3.19 to -0.98]; p = .0002). A higher dosage of BTX-A (60-100 U bilaterally) was associated with a greater reduction in pain at 6 months (MD [95% CI] = -2.98 [-3.52, -2.44]; p < .001). BTX-A also resulted in decreased masseter muscle intensity (µV) (MD [95% CI] = -44.43 [-71.33, -17.53]; p = .001) at 1 month and occlusal force (kg) at 3 months (MD [95% CI] = -30.29 [-48.22 to -12.37]; p = .0009). There was no significant difference in adverse events between BTX-A and placebo. CONCLUSIONS: BTX-A is a safe and effective treatment for reducing pain and improving temporomandibular muscle and joint function in muscular TMD patients. A bilateral dose of 60-100 U might be an optimal choice for treating muscular TMD pain.

Pain Management Strategies for Botulinum Toxin Type A Injections in Children: A Comprehensive National Survey and Procedural Protocol.

INTRODUCTION: Botulinum toxin type A injections are a first-line treatment for spasticity in children. Our purpose is to delineate the national landscape concerning pain management for botulinum toxin type A injections in pediatric patients and to formulate a protocol grounded in current scientific evidence. METHODS: We conducted a nationwide survey targeting physical medicine and rehabilitation specialists performing botulinum toxin type A injections for focal spasticity in children in Portugal. We conducted a literature review to compare the survey results with clinical guidelines, good practice manuals, and protocols published in the literature. Finally, we developed a procedural protocol for pain management in botulinum toxin procedures. RESULTS: The survey was completed by 17 out of 18 identified specialists. All but one use some form of periprocedural analgesia. Five do not use any type of sedation. The majority do not assess pain during the procedures. From the reviewed articles, we obtained 23 articles, 19 of which provided data for detailed analysis. CONCLUSIONS: A prevailing concern centers around pain management during botulinum toxin procedures in children. Nevertheless, a distinct absence of uniformity persists in appraising and managing procedure-related pain. This notion is further underscored by the marked heterogeneity and paucity of published literature within this realm. The systematic implementation of a procedural protocol thus becomes highly crucial.

Persistent myogenic temporomandibular disorders: Are navigation-guided botulinum toxin-A injections into the lateral pterygoid muscles effective?

BACKGROUND: Botulinum toxin has proven effective in treating persistent myogenous temporomandibular disorders (M-TMDs) unresponsive to conservative therapies. While the usual injection sites are the masseter and temporalis muscles, the deeper lateral pterygoid muscle (LPM) is often overlooked due to its difficulty of access and the risk of local complications. This study aims to evaluate the effectiveness of botulinum toxin-A injections (BTX-A) in the LPM with MR-guided navigation of patients with persistent M-TMDs. METHODS: This retrospective study enrolled 34 patients suffering from M-TMDs despite conservative therapies with a total of 51 injection sessions. All of them were treated by BTX-A injections in the LPM using MR-guided navigation, masseter and temporalis with clinical guidance. The effectiveness of the treatment was evaluated with measures of maximum pain-intensity scores of breakthrough and background pain, maximal interincisal mouth opening (MIO), and the presence of joint sounds. The assessment was conducted before injections, and subsequently, at 1 and 3 months postoperatively. Adverse events and perception of improvement with the treatment were also reported for each injection sessions. RESULTS: BTX-A injections in the LPM significantly improved pain scores intensity with a reduction of 65 % and 49 % respectively at the 1- and 3-month follow-ups, with peak effectiveness at 1 month. This study showed also a statistically significant improvement in mean MIO at 3 months post-injection and a decrease in joint sounds with persistence in 9,7 % of cases at 3-month follow-up compared to 41,2 % at baseline. No significant adverse events were observed. Patients treated with BTX-A injections in the LPM had a subjective complete improvement in their perception of treatment efficacy in 63 % of cases at the end of the follow-up period. CONCLUSIONS: This study reports clinical experience on the use of MR-guided navigation to perform accurate, reliable, and safe BTX-A injections in the LPM. Although our results appear to be encouraging regarding symptom improvement of patients suffering from persistent M-TMDs, this approach may not be feasible as a primary standard procedure for managing M-TMDs. Further research is necessary to explore potential reproducible, safe, and cost-effective alternatives to enhance the accessibility of the LPM in clinical practice.

The significance of split-face studies and electromyography in forehead rejuvenation.

BACKGROUND: Botulinum toxin is a neurotoxic substance with a wide range of uses, from the treatment of musculoskeletal spasms to antiaging regimens by improving wrinkles. Split-face studies in which drugs are injected in the right and left sides of the faces have been actively conducted in botulinum toxin studies. In this study, we aimed to investigate the reliability of a split-face study for determining the effectiveness of botulinum toxin based on eyebrow height and movement, and electromyography results. METHODS: Thirty-one women aged 35 to 55 years were included in the study. Eyebrow height was measured as the distance from the eyebrows to the upper eyelid margin on the primary gaze, and eyebrow movement was measured as the distance when the forehead was wrinkled for 5 seconds. A noninvasive method was used for electromyography of the frontalis muscles. RESULTS: No statistically significant differences in right and left eyebrow heights and movements, and electromyography findings (p= 0.256, p= 1.000, and p= 0.978, respectively) were found. Pearson correlation analysis showed that electromyography muscle activity is positively associated with eyebrow movement, respectively (p< 0.001). CONCLUSION: We advocate the reliability of split-face study and the usefulness of electromyography of frontalis muscle in forehead rejuvenation research.

Effectiveness of Botulinum Toxin in the Treatment of Neuropathic Pain: A Literature Review.

Neuralgia is characterized by chronic pain resulting from damage or diseases in the somatosensory system, including nerves responsible for transmitting sensory information. Current treatments for neuropathic pain, which is a type of neuralgia, have limited success rates and can cause unwanted side effects. Since 1989, botulinum toxin-A (BTX-A), derived from the potent neurotoxin Clostridium botulinum, has been used to treat neuropathic pain in humans. BTX-A has shown analgesic effects by inhibiting the release of neurotransmitters involved in pain transmission. This review aims to evaluate the effectiveness of BTX-A in various types of neuralgia. The research question guiding this review is whether BTX-A is safe and effective in reducing pain in different types of neuralgias. To conduct this review, a literature search was performed using the PubMed, Medline, and PubMed Central databases. The search strategy included relevant keywords related to BTX-A, neuralgia, and neuropathic pain. After screening titles, abstracts, and full texts, a total of 30 articles were included in the review. These studies examined the efficacy of BTX-A in various conditions such as postherpetic neuralgia (PHN), auriculotemporal neuralgia (ATN), occipital neuralgia (ON), leprosy-induced neuropathic pain (LIN), focal painful neuropathies, complex regional pain syndrome (CRPS), trigeminal neuralgia (TN), and neuropathic pain associated with spinal cord injury. However, further research is needed to enhance our understanding of the optimal use of BTX-A in specific neuralgias. It is important to acknowledge the limitations of the included studies. Nevertheless, BTX-A might be considered a viable treatment option for neuralgia.

Guidelines for the Use of Botulinum Toxin in Otolaryngology From the Korean Society of Laryngology, Phoniatrics and Logopedics Guideline Task Force.

The Korean Society of Laryngology, Phoniatrics and Logopedics created a task force to establish clinical practice guidelines for the use of botulinum toxin (BT) in otolaryngology. We selected 10 disease categories: spasmodic dysphonia, essential vocal tremor, vocal fold granuloma, bilateral vocal fold paralysis, Frey's syndrome, sialocele, sialorrhea, cricopharyngeal dysfunction, chronic sialadenitis, and first bite syndrome. To retrieve all relevant papers, we searched the CORE databases with predefined search strategies, including Medline (PubMed), Embase, the Cochrane Library, and KoreaMed. The committee reported 13 final recommendations with detailed evidence profiles. The guidelines are primarily aimed at all clinicians applying BT to the head and neck area. In addition, the guidelines aim to promote an improved understanding of the safe and effective use of BT by policymakers and counselors, as well as in patients scheduled to receive BT injections.

A technology evaluation of the atypical use of a CPP-containing peptide in the formulation and performance of a clinical botulinum toxin product.

INTRODUCTION: Cell-penetrating peptides (CPPs), are small peptides that facilitate cytosolic access and, thus, transport of therapeutic macromolecules to intracellular sites when conjugated to cargo proteins. As with all new delivery platforms, clinical development of CPP-containing therapeutics has faced considerable challenges. AREAS COVERED: RTP004 is a novel, 35-amino acid, bi-CPP-containing excipient that binds noncovalently with its cargo (botulinum toxin type A) rather than conjugated as a fusion protein. An RTP004-containing neurotoxin formulation, daxibotulinumtoxinA-lanm for injection (DAXI), has recently been approved by the FDA. The formulation and pharmacological characteristics of RTP004 and the efficacy and safety of the RTP004-neurotoxin formulation are discussed. EXPERT OPINION: RTP004 is a highly positively charged lysine- and arginine-rich structure that provides formulation stability, preventing self-aggregation of the cargo protein and adsorption to container surfaces. The presence of RTP004 in the formulation also appears to increase presynaptic binding of the neurotoxin, reduces post-injection diffusion, and thus facilitates an increase in the cleavage of the intracellular substrate for the botulinum toxin, likely through enhanced cellular uptake. The RTP004-neurotoxin formulation is the first CPP-containing product approved for clinical use. The potential for RTP004 to facilitate other therapeutic cargo molecules requires further research.

Gait analysis patterns and rehabilitative interventions to improve gait in persons with hereditary spastic paraplegia: a systematic review and meta-analysis.

Background: Hereditary spastic paraplegias (HSPs) are a group of inheritance diseases resulting in gait abnormalities, which may be detected using instrumented gait analysis. The aim of this systematic review was 2-fold: to identify specific gait analysis patterns and interventions improving gait in HSP subjects. Methods: A systematic review was conducted in PubMed, Cochrane Library, REHABDATA, and PEDro databases, in accordance with reporting guidelines of PRISMA statement and Cochrane's recommendation. The review protocol was recorded on the PROSPERO register. Patients with pure and complicated HSP of any age were included. All types of studies were included. Risk of bias, quality assessment, and meta-analysis were performed. Results: Forty-two studies were included: 19 were related to gait analysis patterns, and 24 were intervention studies. The latter ones were limited to adults. HSP gait patterns were similar to cerebral palsy in younger subjects and stroke in adults. Knee hyperextension, reduced range of motion at knee, ankle, and hip, reduced foot lift, and increased rapid trunk and arm movements were reported. Botulinum injections reduced spasticity but uncovered weakness and improved gait velocity at follow-up. Weak evidence supported intrathecal baclofen, active intensive physical therapy (i.e., robot-assisted gait training, functional exercises, and hydrotherapy), and functional electrical stimulation. Some improvements but adverse events were reported after transcranial magnetic stimulation, transcutaneous spinal direct current stimulation, and spinal cord stimulation implant. Conclusion: Knee hyperextension, non-sagittal pelvic movements, and reduced ROM at the knee, ankle, and hip represent the most peculiar patterns in HSP, compared to diplegic cerebral palsy and stroke. Botulinum improved comfortable gait velocity after 2 months. Nonetheless, interventions reducing spasticity might result in ineffective functional outcomes unveiling weakness. Intensive active physical therapy and FES might improve gait velocity in the very short term.

Botulinum toxin A in complex incisional hernia repair: a systematic review.

PURPOSE: To evaluate the safety, efficacy, and short and long-term postoperative results of using BTA. METHODS: We conducted a systematic review following the recommendations of the PRISMA method. We systematically reviewed the MEDLINE/PubMed and SCOPUS electronic databases for studies published between January 2010 and September 2021. This systematic review was registered in PROSPERO, with registration number CRD42021252445. RESULTS: After applying the selection criteria, 11 relevant articles were selected. The total sample size was 1058 patients. Most studies aimed to assess the rate of fascial closure, followed by the rate of recurrence and reporting of postoperative complications, as well as the need for the components separation technique (CST). None of the studies reported serious complications from using BTA. Regarding fascial closure, all articles had rates above 75%, except for one. Surgical site events ranged between 19% and 29.4%. No recurrence in the group that used BTA was recorded in five studies. The other articles reported recurrence rates ranging from 6.4 to 11.4% in the groups that received BTA. The studies had varying follow-up times ranging from 1 to 49 months, with a mean of 18.6 months (± 11.2). CONCLUSION: This review described most of the key points about the preoperative use of BTA in hernia repair. It can be concluded that the use of BTA is a safe and effective practice that promotes good short and long-term results. However, the limitations of the current literature prevent more accurate conclusions on the subject.

Unilateral Hypofunction of the Masseter Leads to Molecular and 3D Morphometric Signs of Atrophy in Ipsilateral Agonist Masticatory Muscles in Adult Mice.

Mice are commonly used to study mandibular dynamics due to their similarity in chewing cycle patterns with humans. Adult mice treated unilaterally with botulinum toxin type A (BoNTA) in the masseter exhibit atrophy of this muscle characterized by an increase in the gene expression of atrophy-related molecular markers, and a reduction in both muscle fiber diameter and muscle mass at 14d. However, the impact of this muscle imbalance on the non-treated masticatory muscles remains unexplored. Here, we hypothesize that the unilateral masseter hypofunction leads to molecular and 3D morphometric signs of atrophy of the masseter and its agonist masticatory muscles in adult mice. Twenty-three 8-week-old male BALB/c mice received a single injection of BoNTA in the right masseter, whereas the left masseter received the same volume of saline solution (control side). Animals were euthanized at 2d, 7d, and 14d, and the masticatory muscles were analyzed for mRNA expression. Five heads were harvested at 14d, fixed, stained with a contrast-enhanced agent, and scanned using X-ray microtomography. The three-dimensional morphometric parameters (the volume and thickness) from muscles in situ were obtained. Atrogin-1/MAFbx, MuRF-1, and Myogenin mRNA gene expression were significantly increased at 2 and 7d for both the masseter and temporalis from the BoNTA side. For medial pterygoid, increased mRNA gene expression was found at 7d for Atrogin-1/MAFbx and at 2d-7d for Myogenin. Both the volume and thickness of the masseter, temporalis, and medial pterygoid muscles from the BoNTA side were significantly reduced at 14d. In contrast, the lateral pterygoid from the BoNTA side showed a significant increase in volume at 14d. Therefore, the unilateral hypofunction of the masseter leads to molecular and morphological signs of atrophy in both the BoNTA-injected muscle and its agonistic non-injected masticatory muscles. The generalized effect on the mouse masticatory apparatus when one of its components is intervened suggests the need for more clinical studies to determine the safety of BoNTA usage in clinical dentistry.

The effectiveness and safety of botulinum toxin injections for the treatment of sialorrhea with Parkinson's disease: a systematic review and meta-analysis.

BACKGROUND: Botulinum toxin (BoNT) injection is an important adjunctive method to treat sialorrhea. The purpose of this systematic review was to analyze the effect and safety of BoNT injections in the intervention of sialorrhea with Parkinson's disease (PD). METHODS: We searched PubMed, Web Of Science (WOS), Scopus, Cochrane CENTRAL, and Embase from inception until April 2022. Randomized controlled trials or randomized crossover trials comparing BoNT with placebo in sialorrhea with PD were eligible. PRISMA guidelines were used to carry out the meta-analysis. The Drooling Severity Frequency Scale (DSFS) score and the number of adverse events (AEs) were the primary and secondary outcomes, respectively. Standardized mean differences (SMDs) and risk differences (RDs) are used to express continuous and categorical outcomes, respectively. Heterogeneity among these studies was evaluated using I2 tests. We used the GRADE tool to assess the certainty of evidence (COE). RESULTS: Eight articles involving 259 patients compared BoNT injections with a placebo for PD with sialorrhea. This meta-analysis showed a significant reduction in DSFS scores between BoNT injections and placebo (SMD=-0.98; 95% CI, -1.27 to 0.70, p<0.001; COE: high). This meta-analysis showed a significant difference in AEs between BoNT injections and placebo (RD=0.15; 95% CI, 0.05 to 0.24, p=0.002; COE: low). CONCLUSIONS: The pooled results suggest that BoNT injections have some effect on DSFS scores with sialorrhea caused by PD. There are also mild adverse events, which generally recover within a week or so. The results indicate that BoNT injection is one of the treatments for sialorrhea caused by PD, but we need to pay attention to adverse events. In addition, the follow-up time was extended to observe oral hygiene, ulceration or dental caries, and digestive function. TRIAL REGISTRATION: Our review protocol was registered on PROSPERO (42021288334).