Effect Of Botulinum Toxin A Research Articles

Investigating the impact of botulinum toxin type a on the migration of normal human dermal fibroblasts: An invitro wound healing assay.

Botulinum toxin A (BoNT-A) is widely utilized in the management of hypertrophic and keloid scars. One proposed mechanism for scar prevention involves the inhibition of fibroblast migration in scars by BoNT-A. However, the data regarding the effect of BoNT-A on the migration of normal human dermal fibroblasts (NHDF) is limited. The aim of this study was to investigate the inhibitory effect of different types and dilutions of BoNT-A on the migration of NHDF. In vitro scratch wound assay, NHDF cells were cultured, incubated, and subjected to scratching using a sterile tip. Subsequently, the scratched NHDF monolayer was treated with different types of BoNT-A, including onabotulinumtoxinA (ONA), incobotulinumtoxinA (INCO), prabotulinumtoxinA (PRABO), or letibotulinumtoxinA (LETI), at varying concentrations of 10, 20, 25, 40, 50, and 100 units/milliliter (U/mL). Additionally, abobotulinumtoxinA (ABO) was administered at concentrations of 33, 50, 66, 71, 100, 150, 300, and 500 U/mL. Normal saline solution (NSS) served as a negative control. The extent of NHDF migration was evaluated by comparing each dilution of BoNT-A with the controls using high-content imaging at the 48-h time point. Furthermore, the viability of the of NHDF was assessed. The concentrations of 25, 40, and 50 U/mL of ONA (p < 0.001) and 25 U/mL of LETI (p < 0.05) demonstrated significantly inhibited NHDF migration in comparison to the control group. Conversely, all dilutions of PRABO, INCO, and ABO exhibited comparable NHDF migration to that of the control group. Regarding NHDF viability, no significant decrease was observed across any of the BoNT-A types and dilutions. Different types and dilutions of BoNT-A demonstrated variable inhibitory effects on NHDF migration invitro. The selection of BoNT-A formulation may significantly impact the clinical outcome of scar prevention related to fibroblast migration.

Botulinum Toxin A for the management of temporomandibular myofascial pain - a cohort study

Myofascial pain represents the largest subgroup of TMD (Temporomandibular Disorders), which accounts for a common cause of non-dental orofacial pain. The management of TMD is complex, due to the chronic nature of the condition, alongside acute episodes presenting to the clinician. A fundamental part of TMD management is consideration of the bio-psycho-social element in the aetiology of TMD. First-line treatment of myofascial TMD includes; early diagnosis, explanation and education and conservative self-care measures. More recently, Botulinum Toxin A (BTX-A) is being used increasingly as an adjunct to conservative management of muskulo-skeletal pain disorders, due to its muscle-relaxant and analgesic properties. However, the scientific evidence regarding this is conflicting and it has been suggested that there is insufficient evidence to support the efficacy of BTX-A. A mixed method analysis of a TMD-myofascial pain cohort who underwent BTX-A injections to assess the effectiveness of masseteric BTX-A was carried out. 149 patients completed one round of masseteric BTX-A treatment, of whom 61 completed an additional round of BTX-A. In total, 398 masseter muscles were injected. The average VAS pain score pre-operatively was 8/10, compared with a postoperative mean score of 3/10 at 6 weeks after treatment. The mean percentage reduction in pain was 50%. Pain scores were classified as mild (≤4) , moderate (≤7) or severe (≥8). Pain scores and quality of life scores were found to improve considerably more in the severe pain group in comparison to the mild group. Complete resolution of symptoms was reported in 21% of patients (n=31). The treatment significantly improved patients’ reported pain and quality of life scores, highlighting key beneficial effects for the myofascial pain subgroup of TMD.

Botulinum toxin-A in acute acquired comitant esotropia during COVID pandemic in children and young adolescents

Abstract Purpose: To study the effectiveness of botulinum toxin A (BTX-A) in the treatment of patients with acute acquired comitant esotropia (AACE) due to excessive use of mobile and laptops in the COVID era in the pediatric population and adolescents. Methods: This was a retrospective, interventional study of pediatric patients and young adults who presented with AACE and received unilateral or bilateral BTX-A. All the patients complained of binocular diplopia and sudden onset of esotropia with a history of mobile or laptop usage during the COVID era (2020–2023). Twenty-seven patients with acute-onset esotropia in 3 years (2020–2023) were included. All patients were administered 2.5–7.5 units of BTX-A (Botox, Allergan, India) into the unilateral or bilateral medial rectus muscle of the deviating eye under short general anesthesia or local anesthesia. The main outcome measures were pre- and post-injection angle of deviation, pre- and post-injection stereopsis, final level of stereopsis achieved, recurrence, and whether strabismus surgery was later required. Results: The mean age of patients was 12.85 ± 7.15 years (range: 4–25 years). The mean dosage of Botox was 6 U (2.5–7.5 U). The mean follow-up was 6 months (6 months–2 years). The mean preoperative angle of deviation (AOD) was 41.11 ± 10.9 prism diopters (PD) for distance and 41.67 ± 10.9 PD for near. The maximum effect of BTX-A was seen at 1 month; post-injection AOD was 13.65 ± 14.7 PD for distance and 14.87 ± 15.8 PD for near (P &lt; 0.001). Over half of the patients achieved optimal outcomes, with improvements in stereopsis and sensory fusion. Early intervention (within 3 months of symptom onset) significantly correlated with treatment success. Conclusion: While BTX-A therapy for acute-onset esotropia demonstrates efficacy, patient-specific considerations are essential. This study highlights the evolving nature in the digital age and early administration of BTX-A along with close follow-up to monitor residual and recurrence of esotropia. The surgical intervention can increase the final success rate.

Improving the Retention Rate of Fat Grafting by Botulinum Toxin A: A Randomized, Self-controlled, Clinical Trial.

Botulinum toxin A (BTX-A) can enhance the efficacy of fat grafting. However, most studies conducted animal experiments, lacked objective clinical data, or were non-randomized controlled trials. Thus, objective evaluation of the clinical effectiveness of BTX-A is still elusive. A randomized, self-controlled trial (2020-2022) on 16 patients who underwent bilateral autogenous fat breast augmentation was performed with each patient receiving autologous fat graft and BTX-A on one side and fat graft and equal volume of saline on the other side. All patients were followed. The effects of BTX-A were evaluated objectively by comparing the remaining bilateral fat graft volumes obtained through digital three-dimensional reconstruction. The improvement of each breast appearance and complication were assessed by the physician and patients who were blinded to the treatment. The outcome of fat breast augmentation was evident for both sides at follow-up with no evidence of fat embolism, vascular/nervous injury, infection, and prolonged bruising. The analysis of the three-dimensional reconstruction data and assessments from both physicians and patients showed significant differences in the fat graft retention volume between the BTX-A side and the control side. No significant difference was found in the incidence of complications between the two sides. Autogenous fat breast augmentation is safe and effective. This study shows that BTX-A can significantly improve the retention rate of fat transplantation, but cannot reduce complications. Trial registration This study was registered prior to patient enrollment (ClinicalTrials.gov identifier:ChiCTR2100054878). This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Intradermal Botulinum Toxin A on Skin Quality and Facial Rejuvenation: A Systematic Review and Meta-analysis.

Botulinum toxin A (BTxA) has gained popularity as a nonsurgical aesthetic treatment for skin rejuvenation. However, previous studies on intradermal BTxA have shown inconsistent results. This systematic review and meta-analysis with trial sequential analysis aimed to assess the efficacy and safety of intradermal BTxA for facial rejuvenation. Following PRISMA guidelines, a comprehensive search was conducted in various databases from January 2008 to March 2023. Outcome measures included sebum production, pore size, skin hydration, skin texture, erythema index, facial wrinkles, and facelift. Eligible studies included human-based clinical trials and prospective cohort studies published in English, focusing on healthy populations requiring facial rejuvenation. Two authors independently screened the titles and abstracts, followed by a full-text review to determine study eligibility. Data extraction and quality assessment were performed by two authors using predefined criteria. Ten studies met the inclusion criteria, including five randomized controlled trials and five prospective cohort studies with 153 participants. Studies revealed positive effects of intradermal BTxA on various outcome measures related to facial rejuvenation. These effects included improvements in sebum production, pore size, erythema index, facial wrinkles, skin texture and elasticity, and overall facelift but not skin hydration. All failed to reach the required information size in the trial sequential analysis. Findings suggest positive outcomes in multiple attributes of skin quality and facial rejuvenation. However, more high-quality research is needed to establish definitive conclusions. These findings contribute to the evidence base for nonsurgical aesthetic treatments, emphasizing the importance of ongoing research in this field.

Gait Reconstruction Strategy Using Botulinum Toxin Therapy Combined with Rehabilitation.

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

Botulinum Toxin-A for the Treatment of Myogenous Temporomandibular Disorders: An Umbrella Review of Systematic Reviews.

Temporomandibular disorders (TMDs) encompass several conditions that cause pain and impair function of the masticatory muscles (M-TMDs) and temporomandibular joints. There is a large interest among clinicians and researchers in the use of botulinum toxin-A (BoNT-A) as a treatment for M-TMD. However, due to the lack of consistent evidence regarding the efficacy as well as adverse events of BoNT-A, clinical decision making is challenging. Therefore, this umbrella review aimed to systematically assess systematic reviews (SRs) evaluating BoNT-A treatment effects on pain intensity, mandibular movements, and adverse events in patients with M-TMDs. An electronic search was undertaken in the databases MEDLINE, EMBASE, CINAHL, Cochrane Central Registry of Controlled Trials (CENTRAL), Web of Science, Epistemonikos, ClinicalTrials.gov, and ICTRP to identify SRs investigating BoNT-A effects on M-TMDs, published from the inception of each database until 6 December 2023. The quality of evidence was rated according to the critical appraisalchecklist developed by the umbrella review methodology working group. Only high-quality SRs were included. In total, 18 SRs were included. BoNT-A was shown to be more effective than placebo to reduce pain intensity, but not compared to standard treatments. Additionally, BoNT-A was not superior to placebo or standard treatments regarding improvement of mandibular movements. BoNT-A was considered to have a higher risk for adverse events on muscle and bony tissue compared with other treatments. The synthesis in this umbrella review provides the highest level of evidence present. Taken together, there are indications of effectiveness of BoNT-A for treatment of M-TMDs, supported by moderate evidence. However, considering the risk of causing serious adverse events, treatment with BoNT-A is recommended to be the last treatment alternative.

The Impact of Botulinum Toxin Combined with Robot-Assisted Gait Training on Spasticity and Gross Motor Function on Children with Spastic Cerebral Palsy

ABSTRACT Objective To evaluate the impact of combining botulinum toxin-A (BoNT-A) injection with robot-assisted gait training (RAGT) on lower limb spasticity and motor function in children with cerebral palsy. Methods A prospective study was conducted from January 2020 to January 2023, including 68 patients. Twenty patients received the combination of BoNT-A injection and RAGT, while 48 received BoNT-A injection alone. Assessments were performed before the intervention and at 1, 3, and 6 months post-injection using the Modified Tardieu Scale (MTS), sections D and E of the Gross Motor Function Measure-88 (GMFM-88), 6-minute walk test (6MWT), and 10-meter walk test (10MWT). Results Compared to the control group receiving BoNT-A alone, the combination of BoNT-A and RAGT did not significantly improve spasticity-related outcomes, including MTS scores, R1, and R2 angles (p > .05). However, the combination group demonstrated significantly improved gross motor function, particularly in walking, running (GMFM-E), short-term walking endurance (6MWT), and walking speed (10MWT) in children with cerebral palsy after the intervention (p < .05). Conclusion While the addition of RAGT did not enhance the anti-spasticity effects of BoNT-A, it significantly improved gross motor function and walking abilities in children with cerebral palsy.

Botulinum toxin-A effects on pain, somatosensory and psychosocial features of patients with refractory masticatory myofascial pain: a randomized double-blind clinical trial

The antinociceptive effect of BoNT-A have been well documented in animal studies; however, results of few but well-designed randomized placebo-controlled clinical trials about BoNT-A efficacy in masticatory myofascial pain (MFP) are inconsistent. Therefore, the present randomized, double-blind, placebo-controlled clinical trial evaluated the efficacy of BoNT-A in patients with refractory MFP. Twenty-eight patients with pain reduction of less than 30% despite conservative treatment and with an average pain intensity of > 50 mm on the visual analogue scale (VAS) participated. Patients were randomly assigned to receive a total of 80 U of BoNT-A or saline solution (SS) injected into the masseter and anterior temporalis muscles. Pain intensity (VAS), quantitative sensory testing (QST), conditioned pain modulation (CPM), and psychosocial status were examined. Follow-up was performed at 1 and 6 months. For repeated-measure comparisons between evaluation times, Friedman test with Bonferroni correction was used for pain and somatosensory variables and the Wilcoxon test for the psychosocial variables. The Mann–Whitney test was used for all comparisons between groups. The BoNT-A group had a significant decrease in pain intensity at follow-ups compared with the SS group (p < 0.001). QST assessment revealed higher pressure pain threshold values in the masseter muscle for BoNT-A group compared to SS (p < 0.03) at all follow-ups. No differences were found for mechanical pain threshold and wind-up ratio values (p > 0.05) in the entire study. The BoNT-A group presented the most efficient CPM effect (p < 0.03) only at the 1 month follow-up in the masseter muscle. There was a significant time effect for BoNT-A in all psychosocial variables (p < 0.05) and a drug effect in the Central Sensitization Inventory (p < 0.01), Pittsburgh Sleep Quality Index (p < 0.004), and Healthy Survey 36 (p < 0.05) at 6 months follow-up. The study demonstrates that a single injection-session of BoNT-A has positive effects on the hall pain spectrum of patients with refractory masticatory myofascial pain.

Beyond neuromuscular activity: botulinum toxin type A exerts direct central action on spinal control of movement

Overt muscle activity and impaired spinal locomotor control hampering coordinated movement is a hallmark of spasticity and movement disorders like dystonia. While botulinum toxin A (BoNT-A) standard therapy alleviates mentioned symptoms presumably due to its peripheral neuromuscular actions alone, the aim of present study was to examine for the first time the toxin's trans-synaptic activity within central circuits that govern the skilled movement. The rat hindlimb motor pools were targeted by BoNT-A intrasciatic bilateral injection (2 U per nerve), while its trans-synaptic action on premotor inputs was blocked by intrathecal BoNT-A–neutralising antitoxin (5 i.u.). Effects of BoNT-A on coordinated and high intensity motor tasks (rotarod, beamwalk swimming), and localised muscle weakness (digit abduction, gait ability) were followed until their substantial recovery by day 56 post BoNT-A. Later, (day 62–77) the BoNT-A effects were examined in unilateral calf muscle spasm evoked by tetanus toxin (TeNT, 1.5 ng). In comparison to peripheral effect alone, combined peripheral and central trans-synaptic BoNT-A action induced a more prominent and longer impairment of different motor tasks, as well as the localised muscle weakness. After near-complete recovery of motor functions, the BoNT-A maintained the ability to reduce the experimental calf spasm evoked by tetanus toxin (TeNT 1.5 ng, day 62) without altering the monosynaptic reflex excitability. These results indicate that, in addition to muscle terminals, BoNT-A-mediated control of hyperactive muscle activity in movement disorders and spasticity may involve the spinal premotor inputs and central circuits participating in the skilled locomotor performance.

Effectiveness of Botulinum Toxin-A on Face, Head, and Neck Scars: A Systematic Review and Meta-Analysis.

Background: Botulinum toxin A (BTA) temporarily paralyzes nearby muscles to reduce tension in wound sites, inhibiting scar hyperplasia. Objective: To evaluate the effectiveness of BTA injection on scar formation and quality in various face, head, and neck sites. Methods: A comprehensive search was conducted across four electronic databases and registries to identify relevant studies. We assessed the following outcomes: visual analog scale (VAS), Vancouver scar scale (VSS), scar width, patient self-assessment scale, Stony Brook scar evaluation scales, Observer scar assessment scale, Manchester scar scale, and patient scar-assessment scale. Results: This systematic review included 20 studies encompassing 894 patients, of which, 18 studies were eligible for meta-analysis. The VAS and VSS significantly improved with BTA compared to controls which significantly reduced scar width at the first and second measurement points compared to controls. Subgroup analyses revealed that BTA had better upper lip and forehead outcomes. Conclusion: This systematic review and meta-analysis found that scars of the face, head, and neck were improved with BTA treatment compared to controls. This highlights the need for further study, especially concentrating on the upper lip and forehead regions, where improved outcomes were identified on subgroup analysis.

Effect of botulinum toxin type A in functionality, synkinesis and quality of life in peripheral facial palsy sequelae

ObjectivesThis study aimed to assess the effects of botulinum toxin A (BTX-A) infiltration on face muscle function, synkinesis, and quality of life in patients with sequelae of peripheral facial palsy (PFP). Material and methodsWe present the results of a prospective study including a sample of 20 patients with sequelae of PFP (15 women, 5 men) who underwent BTX-A (Botox© or Xeomin©) infiltration. All patients had previously received personalised treatment with neuromuscular retraining. A clinical assessment was performed before BTX-A infiltration and 4 weeks after treatment. The effect of BTX-A on face muscle function, quality of life, and synkinesis was evaluated using the Sunnybrook Facial Grading System (SFGS), the Facial Clinimetric Evaluation (FaCE) questionnaire, and the Synkinesis Assessment Questionnaire (SAQ), respectively. ResultsMean SFGS scores increased from 64.8 to 69.9 after BTX-A infiltration (P=.004). Increases were also observed in mean total FaCE scores (from 52.42 to 64.5; P<.001) and the mean score on the FaCE social function subscale (from 61.15 to 78.44; P<.001). Mean SAQ scores decreased from 46.22 to 37.55 after BTX-A infiltration (P=.001). ConclusionsBTX-A infiltration increases face muscle function, improves quality of life, and reduces synkinesis in patients with sequelae of PFP.

Non-Surgical Management of the Gingival Smile with Botulinum Toxin A-A Systematic Review and Meta-Analysis.

Currently, concern about facial attractiveness is increasing, and this fact has led to orthodontics in adult patients being an increasingly demanded treatment, and with it, multi-disciplinary work. When it is caused by a vertical excess of the maxilla, the ideal solution is orthognathic surgery. However, in borderline cases and when the cause is hyperactivity of the upper lip levator muscle complex, alternative conservative solutions can be considered, such as the application of botulinum toxin A (BTX-A). Botulinum toxin is a protein produced by a bacterium and causes a reduction in the force of muscle contraction. The multi-factorial nature of the smile requires an individualized diagnosis in each patient, since there are multiple ways to treat the gummy smile (orthognathic surgery, gingivoplasty, orthodontic intrusion). In recent years, interest has grown in the simplest techniques that allow the patient to quickly return to their usual routine, such as lip replacement. However, this procedure shows recurrences in the first 6-8 post-operative weeks. The main objective of this systematic review and meta-analysis is to analyze the effectiveness of BTX-A in the treatment of gummy smile in the short term, to study its stability, and to evaluate potential complications. A thorough search of the PubMed, Scopus, Embase, Web of Science, and Cochrane databases and a grey literature search were conducted. The inclusion criteria were studies with a sample size greater than or equal to 10 patients with gingival exposure greater than 2 mm in smile, treated with BTX-A infiltration. Those patients whose exclusive etiology of their gummy smile was related to altered passive eruption, gingival thickening, or overeruption of upper incisors were excluded. In the qualitative analysis, the mean pre-treatment gingival exposure ranged between 3.5 and 7.2 mm, reaching a reduction of up to 6 mm after infiltration with botulinum toxin at 12 weeks. Although multiple muscles are involved in the facial expression, the muscles par excellence selected for blockade with BTX-A were levator labii superioris, levator labii superioris ala nasalis, and zygomaticus minor, infiltrating from 1.25 to 7.5 units per side. In the quantitative analysis, the difference in mean reduction between both groups was -2.51 mm at two weeks and -2.24 mm at three months. The benefit of BTX-A in terms of improvement of gummy smile is demonstrated, as a significant reduction in gummy smile is estimated by BTX-A therapy two weeks after its application. Its results gradually decrease over time, however, they stay satisfactory without returning to their initial values after 12 weeks.

The Place of Botulinum Toxin in Spastic Hemiplegic Shoulder Pain after Stroke: A Scoping Review

Stroke is a common pathology worldwide, with an age-standardized global rate of new strokes of 150.5 per 100,000 population in 2017. Stroke causes upper motor neuron impairment leading to a spectrum of muscle weakness around the shoulder joint, changes in muscle tone, and subsequent soft tissue changes. Hemiplegic shoulder pain (HSP) is the most common pain condition in stroke patients and one of the four most common medical complications after stroke. The importance of the appropriate positioning and handling of the hemiplegic shoulder for prevention of HSP is therefore of high clinical relevance. Nevertheless, HSP remains a frequent and disabling problem after stroke, with a 1-year prevalence rate up to 39%. Furthermore, the severity of the motor impairment is one of the most important identified risk factors for HSP in literature. Spasticity is one of these motor impairments that is likely to be modifiable. After ruling out or treating other shoulder pathologies, spasticity must be assessed and treated because it could lead to a cascade of unwanted complications, including spastic HSP. In clinical practice, Botulinum toxin A (BTA) is regarded as the first-choice treatment of focal spasticity in the upper limb, as it gives the opportunity to target specifically selected muscles. It thereby provides the possibility of a unique patient tailored focal and reversible treatment for post stroke spasticity. This scoping review aims to summarize the current evidence of BTA treatment for spastic HSP. First, the clinical manifestation and outcome measures of spastic HSP will be addressed, and second the current evidence of BTA treatment of spastic HSP will be reviewed. We also go in-depth into the elements of BTA application that may optimize the therapeutic effect of BTA. Finally, future considerations for the use of BTA for spastic HSP in clinical practice and research settings will be discussed.

A computed tomography study investigating the effects of botulinum toxin injections prior to complex abdominal wall reconstruction

ObjectiveTo explore how intramuscular injection of botulinum toxin A (BTA) affects the lateral abdominal wall (LAW) musculature, abdominal- and hernia dimensions, and muscle structure on computed tomography (CT) in patients scheduled for complex abdominal wall reconstruction (CAWR).MethodsRetrospective analysis of prospectively registered patients who received bilateral intramuscular BTA injections into all three muscles of the LAW. Only patients for which a CT was available before and 3–6 weeks after BTA treatment prior to surgery were analyzed.ResultsFifty-two patients were analyzed. Median hernia width in all patients decreased with 0.4 cm (IQR − 2.1;0.6) (p = 0.023). Median intra-abdominal transverse diameter increased with 0.9 cm (IQR − 0.2;3.3) (p = 0.001) and the intra-abdominal anterior–posterior diameter decreased with 0.5 cm (IQR − 1.3;0.5) (p = 0.017), making the abdomen more oval. Median LAW muscle length increased with 0.9 cm (IQR 0.0;2.4) per side (p < 0.001), muscle thickness decreased with 0.5 cm (IQR − 0.8;− 0.2) (− 25.0%) per side (p < 0.001), and muscle mass decreased with 3.9 cm2 (IQR − 6.4;-1.5) (− 15.8%) per side (p < 0.001). Median HU of the psoas muscles (density) increased with 4.8 HU (IQR 0.4;9.7) (10.3%) per side (p < 0.001). Effects of BTA were more pronounced in patients with a loss of domain (LoD) ≥ 20%.ConclusionsThe main effect of BTA injections is elongation and thinning of the LAW muscles, more than a decrease in hernia width. Concomitantly, the abdomen becomes more oval. An increase of psoas muscles density is seen, associated with offloading of the LAW muscles. Patients with large LoD have a proportionally higher effect of BTA.

The histologic effects of high doses of botulinum toxin a on the rabbit's salivary gland

The exact mechanism of botulinum toxin A (BTX-A) on submandibular salivary gland (SMG) regarding its function and histology remains unclear. The goal of this work is to clarify the histological effects of BTX-A (at high doses) in SMG in rabbits after one week. Thirty adult male rabbits were used in this study and they arranged as group 1 includes rabbits which received any treatment and kept for one week duration. Group 2 includes rabbits which received 8 units of BTX-A. Group 3 includes rabbits which received 16 units of BTX-A. Animals were euthanized with ether after one week. Specimens of SMG from all rabbits were taken to perform a routine histological preparation and examination. Sections of rabbits of group 2 and group 3 showed evidence of edema that is surrounding striated ducts, congested blood vessels, and even necrosis of both serous and mucous acini. Some sections exhibited features of degeneration of mucous acini. Hemorrhage was noticed in some sections. Injection of either 8 or 16 units of BTX-A induces several alterations in the submandibular glands’ histology.

Negative emotional impact following botulinum toxin treatment for crow's feet lines

So far, studies addressing the negative psychological effects of crow's feet treatment with botulinum toxin A (BoNTA) have rarely been published. BoNTA causes neuromuscular paralysis through a process of chemical denervation, temporarily preventing muscle contraction. The ability of botulinum toxin to alleviate dynamic wrinkles was coincidentally discovered after treating patients for benign essential blepharospasm in 1987.1 Since then, it has been widely used in cosmetic dermatology to reduce wrinkles and rejuvenate the skin. We report the cases of three female patients who presented with negative emotional complaints following BoNTA treatment for crow's feet. A 34-year-old Caucasian woman presented 14 days after the first BoNTA treatment. She reported having been injected with onabotulinumtoxinA (10 units per side) in the lateral part of the orbicularis oculi muscles on both sides. She reported a history of depression, treated with citalopram. The injection pattern was 3-4-3 U (Figures 1a and 2). A 28-year-old Caucasian woman presented 12 days after the first BoNTA treatment. She was injected 20 units of incobotulinumtoxinA (10 units per side) in the lateral part of the musculus orbicularis oculi. Her medical history was not relevant for previous diseases. The injection pattern was 3-4-3 U (Figure 1a). A 56-year-old Caucasian woman presented 10 days after the first BoNTA treatment. In this case, she was injected 50 units of abobotulinumtoxinA (25 units per side) in the lateral part of the musculus orbicularis oculi. Her medical history was only relevant to smoking. The injection pattern was 10-10-10 U (Figure 1b). All three cases were attended in our specialised outpatient clinic at Erasmus MC for complications of injectables, reporting a non-natural smile after BoNTA treatment. All patients reported a mental impact in the form of sadness, distress and insecurities, and a socio-psychological impact manifested as limitations in their daily functions, such as going to work or even going outside. All patients stated that their emotional status was normal before the treatment. Physical examination revealed complete paralysis of the lateral part of the orbicularis oculi muscles, resulting in a non-smooth transition with a crease between the lower eyelid and the cheek area (Figure 2). After explaining the anatomy of this area, mechanisms of action and temporary effect of BoNTA, the patients were reassured with a biweekly follow-up. Upon smiling, the zygomaticus major muscles contraction lifts a ‘shelf’ of cheek tissue and rhytids that stops abruptly as it transitions into the smooth paralysed lateral orbital area.2 Among older patients, this effect can be accentuated and even visible at rest, due to the excess skin in the lower lid.3 For most people, this muscle is also an accessory upper cheek elevator. When the lower portion of the lateral orbicularis oculi is totally paralysed, a small loss of upper cheek elevation is observed, resulting in a weaker facial feedback effect.3, 4 The injection pattern used in all three cases was similar (Figure 1a,b) and the doses between the different toxins were equivalent, reflecting a standardised practice in many current medical settings. Published guidelines for the use of BoNTA are an excellent starting point and an important tool for clinicians with little experience; however, each practitioner is likely to develop their own algorithm for facial rejuvenation procedures.5 Different injection patterns and new techniques, such as the microdroplet technique for BoNTA treatment on crow's feet, may possibly achieve a smoother transition between treated and non-treated areas for a more harmonious and natural outcome.6 Besides, appreciation for the aesthetic result desired by the patient, clear explanations about the mechanism of action of BoNTA and appropriate management of expectations result in a better doctor–patient communication and higher patient satisfaction. We think that the negative psychological effects of BoNTA treatment are under-reported. Although temporary, these effects can be very distressing and may lead to decreased client retention. The report of these cases should raise awareness about the importance of a personalised treatment plan for each patient, based on a deep understanding of the patient's unique characteristics combined with appropriate doctor-patient communication. The authors declare no conflict of interest. The patients in this manuscript have given written informed consent to the publication of their case details. I had full access to all the data in the study and I take responsibility for the integrity of the data and the accuracy of the data analysis as well as the decision to submit for publication.

Endoscopic Intragastric Injection of Botulinum Toxin A in Obese Patients Accelerates Weight Loss after Bariatric Surgery: Follow-Up of a Randomised Controlled Trial (IntraTox Study).

Background: Intragastric injection of botulinum toxin A (BT-A) has been shown to be effective for weight loss up to six months after administration, according to previous studies. Our objective was to determine, in patients on bariatric surgery waiting lists, the effect of BT-A on weight loss in the pre- and postoperative period and to analyse if there are different responses based on Body Mass Index (BMI). Methods: We performed a follow-up analysis of the IntraTox study, which included 46 patients on bariatric surgery waiting lists in a single-centre, randomised, double-blind, placebo-controlled clinical trial. The treatment group received intragastric BT-A, whereas the control group received physiological saline solution. The one-time procedure was performed at the time of diagnostic endoscopy 7–8 months before surgery. Weight loss was evaluated at admission and after 4 and 12 weeks from the bariatric surgery. Our analysis was stratified by BMI at randomisation. Results: weight loss percentage on the day of surgery, with respect to the initial visit, was −4.5 ± 3.9% for the control group vs. −7.6 ± 4.2%, for the treatment group (p = 0.013). Weight loss percentage tended to remain greater in the treatment group one month after the intervention (−12.7 ± 4.7% vs. −15.2 ± 4.6%, p = 0.07) and become similar three months after (−21.6 ± 4.7% vs. −21.6 ± 4.6%). After stratifying by BMI, only patients with BMI over 50 kg/m2 allocated to the treatment group obtained a greater weight loss at the end of the trial, the day of surgery, and one month after, compared with the placebo group (−4.9 ± 4.9%, −10.8 ± 5.3% and −17.1 ± 3.8% vs. −0.1 ± 2.6%, −4.3 ± 3.2% and −12.8 ± 4.1%, respectively (p < 0.05). Conclusions: intragastric injection of BT-A is effective to achieve significant weight loss, especially in extreme obesity. Its use before bariatric surgery enhances perioperative weight loss.

Intracavernosal OnabotulinumtoxinA Exerts a Synergistic Pro-Erectile Effect When Combined With Sildenafil in Spontaneously Hypertensive Rats

Botulinum toxin A (BTX-A) has a variety of uses in medicine. Some evidence suggests that intracavernosal (ic) BTX-A injection administered in addition to phosphodiesterase type 5 inhibitors (PDE5-Is) could effectively treat erectile dysfunction (ED) in insufficient responders to PDE5-Is. To provide experimental pharmacological evidence for the use of onabotulinumtoxinA ic alone or in combination with PDE5-Is for difficult-to-treat ED. We thus compared the effects of BTX-A ic alone and BTX-A ic combined with PDE5-I iv, and a placebo treatment ic or iv. Erectile function was evaluated following cavernous nerve electrical stimulation (6 V, 1-millisecond pulse, 45-second duration) at different frequencies (0, 2, 3, 4, 5, 7.5, and 10 Hz) in 4 groups (n = 8 / group) of anesthetized, spontaneously hypertensive rats, a robust animal model of ED of vascular origin. Rats were treated by onabotulinumtoxinA 10U or saline ic 1 week prior to erectile function testing and sildenafil (0.3 mg/kg) or saline iv 4 minutes prior to testing. Frequency-response curves were compared with a 2 way ANOVA. Both onabotulinumtoxinA ic, and sildenafil iv significantly improved erectile responses in spontaneously hypertensive rats, however the effect was greatly amplified when the treatments were combined. Intracavernosal pressure and/or mean arterial pressure ratios were significantly increased by sildenafil and onabotulinumtoxinA ic versus the control condition. OnabotulinumtoxinA 10U ic combined with sildenafil iv significantly potentiated erectile responses. Area under the curve and/or mean arterial pressure ratio increased by 19% with sildenafil iv, by 15% with onabotulinumtoxinA ic and by 58% with the combined treatment following cavernous nerve electrical stimulation at 6V, 1 ms, 10 Hz: these stimulation parameters elicited the maximal erectile response. These data provide a pharmacological rationale for the combined administration of onabotulinumtoxinA ic and sildenafil iv since the effects of both treatments were potentiated when their administration was combined. First evidence of a synergistic pro-erectile effect of BTX-A combined with PDE5-I, however the mechanism behind the pro-erectile effect of BTX-A ic remains hypothetical. These results support further studies into the mechanisms behind the pro-erectile effect of BTX-A ic, as well as multicenter randomized control trials to evaluate the safety and efficacy of BTX-A ic combined with sildenafil for difficult-to-treat ED.

Botulinum Toxin-A Injection in Chronic Pelvic Pain Syndrome Treatment: A Systematic Review and Pooled Meta-Analysis.

Introduction: Pain management of patients with chronic pelvic pain syndrome (CPPS) is challenging, because pain is often refractory to conventional treatments. Botulinum toxin A (BTX-A) may represent a promising therapeutic strategy for these patients. The aim of this systematic review was to investigate the role of BTX-A in CPPS treatment. Methods: We reviewed the literature for prospective studies evaluating the use of BTX-A in the treatment of CPPS. A comprehensive search in the PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials databases was performed from English language articles published between January 2000 and October 2021. The primary outcome was to evaluate pain improvement in CPPS after BTX-A treatment. Pooled meta-analysis of the included studies, considering the effect of BTX-A on pain evaluated at last available follow-up compared to baseline values, was performed together with meta-regression analysis. Results: After screening 1001 records, 18 full-text manuscripts were selected, comprising 13 randomized clinical trials and five comparative studies. They covered overall 896 patients of both sexes and several subtype of CPPS (interstitial cystitis/bladder pain syndrome, chronic prostatitis/prostate pain syndrome, chronic scrotal pain, gynecological pelvic pain, myofascial pelvic pain). The clinical and methodological heterogeneity of studies included makes it difficult to do an overall estimation of the real effect of BTX-A on pain and other functional outcomes of various CPPS subtypes. However, considering pooled meta-analysis results, a benefit in pain relief was showed for BTX-A-treated patients both in the overall studies populations and in the overall cohorts of patients with CPP due to bladder, prostate, and gynecological origin. Conclusions: BTX-A could be an efficacious treatment for some specific CPPS subtypes. Higher level studies are needed to assess the efficacy and safety of BTX-A and provide objective indications for its use in CPPS management.