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Botulinum toxin type A is a first-line treatment for post-stroke spasticity, with selective action at nerve endings and minimal effects beyond the injection site. However, concerns about potential adverse reactions due to toxin diffusion and spread can significantly influence physicians’ therapeutic decisions in managing post-stroke spasticity. Current evidence shows that while the main formulations of botulinum toxin type A have different molecular weights and sizes, they do not exhibit differing diffusion profiles. Instead, the key factors determining botulinum toxin type A diffusion and spread in post-stroke spasticity management are the dose (i.e., the actual amount of 150 kDa neurotoxin protein injected), dilution, and injection volume. Other injection-related factors, such as the needle gauge and injection speed, have also been suggested to have a secondary influence on botulinum toxin type A diffusion and spread. The needs of patients with post-stroke spasticity may vary, and depending on treatment goals, botulinum toxin type A diffusion and spread can be something to avoid or may offer therapeutic benefits by reaching a greater number of nerve terminals in the target muscle, enhancing the toxin’s effect. These factors should be carefully evaluated in spasticity clinics.

The first-line management of cervical dystonia (CD) symptoms is intramuscular injection of botulinum toxin type A (BoNTA). However, a comparison of safety among BoNTAs is difficult because, per regulatory authorities, units of BoNTA activity are not interchangeable. Dysphagia and muscle weakness are widely considered two key adverse events to monitor closely in the treatment of CD. This integrated analysis compared the safety of BoNTAs approved for CD in the US by evaluating relationships between the incidence of dysphagia and muscle weakness in prescribing information and the core neurotoxin content. Coefficients The coefficients of determination (R2) and trendlines were estimated via regression-based lines of best fit. Adverse drug reaction (ADR) rates were strongly correlated with core neurotoxin amounts for conventional BoNTAs (slope coefficients: dysphagia = 0.048, R2 = 0.74; muscle weakness = 0.096, R2 = 0.82). The published ADR rates at approved doses for conventional BoNTAs were higher compared with DaxibotulinumtoxinA (DAXI; DAXXIFY®, Revance Therapeutics, Inc., Nashville, TN, USA) by core neurotoxin content. The use of a core neurotoxin amount was found to be an effective method for comparing the safety of BoNTA products. Current clinical trials suggest that DAXI, a novel BoNTA formulation, provides a potentially wider safety margin compared with other approved BoNTAs for CD. The lower amount of core neurotoxin administered at approved doses compared with conventional BoNTAs may explain low on-target ADRs like muscle weakness, whereas reduced diffusion from the injection site is thought to be responsible for low off-target ADRs like dysphagia.

Background: Botulinum toxin type A is widely utilized for both therapeutic and aesthetic purposes, yet concerns regarding its immunogenicity have raised issues related to treatment failure and adverse reactions. Objective: This review aims to evaluate the immunogenicity of commercially available botulinum toxin type A products across various clinical indications and identify the risk factors associated with antibody formation. Methods: A comprehensive search of electronic databases was conducted to find studies that investigated the immunogenicity of botulinum toxin type A in patients treated for different conditions. The studies were classified based on the Oxford Center for Evidence-Based Medicine’s evidence hierarchy. Results: The overall incidence of neutralizing antibody formation with botulinum toxin type A treatment is relatively low. However, it varies depending on the indication and is influenced by factors such as the frequency of injections and the cumulative dose. The total cumulative dose and the number of treatment cycles are critical factors in determining the risk of developing antibodies against botulinum toxin type A. Conclusion: This literature review highlights that the immunogenicity of botulinum toxin type A products differs across indications, with repeated injections posing a significant risk for the formation of neutralizing antibodies. The findings underscore the need for further research to better understand antibody formation mechanisms and to develop strategies that minimize their impact on treatment efficacy.

Acquired deforming hypertonia (ADH) affects the daily care of numerous nursing home residents. The aim of this study was to analyze the practice, aims, and effectiveness of botulinum toxin injections (BTxis) in the treatment of older patients with contractures, an indication for which BTxis are still underused. Data were extracted retrospectively from medical records regarding population, contractures, and injections. A prospective analysis was conducted to evaluate treatment goals set by goal attainment scaling (GAS) at T0 and at T1, to evaluate the therapeutic effects. We also recorded the occurrence of side effects, using a telephone questionnaire. This study included 41 patients older than 70 years who had received one or more BTxis for the first time between January 2018 and December 2021. Most of the older people we included lived in an institution (66%), manifested severe dependence, and presented significant morbi-mortality (37% of the patients died in the year after the last injection). The main objectives of these injections were purely comfort, without any functional goals. The GAS scores suggested effectiveness for comfort GAS scores. No complications were recorded. This study highlights the BTxis potential to address the needs of a larger number of older patients with ADH.

Dynamic wrinkle reduction continues to challenge aesthetic dermatology, predominantly addressed through Botulinumtoxin (Botox) injections. Despite Botox’s robust efficacy with up to an 80% reduction in wrinkle visibility within just one week, its invasive administration and specific mechanism of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex inhibition prompt the exploration of safer, non-invasive alternatives. This review critically assesses recent innovations in non-invasive effects, with a focus on peptides and botanical extracts that exhibit a diverse array of mechanisms including SNARE complex inhibition, modulation of calcium and sodium channels, and interactions with acetylcholine receptors, contributing to their effectiveness in muscle relaxation on dynamic wrinkle approaches. Noteworthy peptides such as Argireline and SYN-Ake replicate the neuromodulatory effects of Botox, achieving up to a 52% reduction in wrinkles within four weeks without injections. Moreover, botanical extracts meet the rising demand for clean beauty solutions by enhancing skin elasticity and health through gentle yet potent mechanisms. However, the main concern with peptides is their low absorption rate, with only six clinical validations regarding Botox-like peptide anti-wrinkle efficacy available. These advancements not only deepen our understanding of cosmetic dermatology but also significantly influence market dynamics and consumer behavior, underscoring their pivotal role in redefining the future landscape of anti-aging effects.

To describe the need and effectiveness of acute and preventive medications in a series of 100 consecutive patients referred due to COVID-19-related headaches. Patients were aged 48.0 (standard deviation (SD): 12.4), 84% were female, and 56% had a prior history of headache. The most common headache phenotype was holocranial (63%), frontal (48%), pressing (75%), of moderate intensity (7 out of 10), and accompanied by photophobia (58%). Acute medication was required by 93%, with paracetamol (46%) being the most frequently used drug, followed by ibuprofen (44%). The drugs with the highest proportion of a 2 h pain-freedom response were dexketoprofen (58.8%), triptans (57.7%), and ibuprofen (54.3%). Preventive treatment was required by 75% of patients. The most frequently used drugs were amitriptyline (66%), anesthetic blockades (18%), and onabotulinumtoxinA (11%). The drugs with the highest 50% responder rate were amitriptyline (45.5%), mirtazapine (50%), and anesthetic blockades (38.9%). The highest 75% responder rate was experienced following onabotulinumtoxinA (18.2%). In conclusion, most patients required acute medication, with triptans and non-steroidal anti-inflammatory drugs achieving the best responses. Three-quarters of patients required preventive medication. The most frequently used drug was amitriptyline, which obtained the best results. In some treatment-resistant patients, anesthetic blockades and onabotulinumtoxinA were also beneficial.

Botulinum neurotoxin (BNT) injection into the cricopharyngeus muscle (CPM) under ultrasound (US) guidance is a minimally invasive technique performed to relieve cricopharyngeal dysphagia by reducing CPM spasticity. This technique is basically accessible only to both lateral sides of the CPM. This cadaveric study aimed to evaluate whether US-guided injection could effectively deliver BNT to abundant areas of gross nerve endings within the CPM. We utilized a newly modified Sihler’s staining method to identify regions with abundant neural endings within the CPM while preserving the three-dimensional morphology of the muscle in 10 sides of 5 fresh cadavers. A mixture of 0.2 mL dye was injected into the 16 sides of CPM under US guidance in 8 cadavers. Nerve endings were abundant in posterolateral areas of the CPM; the injected dye was identified at the posterolateral area on 12 sides (12/16 side, 75%) without diffusion into the posterior cricoarytenoid muscle. The injection failed on four sides (two sides of the prevertebral fascia and two sides of the esophagus below the CPM). These results suggest that US-guided injection could be a feasible technique as it can deliver BNT to the most abundant nerve distribution areas within the CPM in most cases.

Botulinum toxin type A (BONT-A) has shown promise in improving the mood-related symptoms of psychiatric disorders by targeting muscles linked to the expression of negative emotions. We conducted a systematic review of past and ongoing efficacy trials of BONT-A therapy for psychiatric disorders to identify relevant trends in the field and discuss the refinement of therapeutic techniques. A comprehensive search for published clinical trials using BONT-A injections for psychiatric disorders was performed on 4 May 2023 through OVID databases (MEDLINE, Embase, APA PsycINFO). Unpublished clinical trials were searched through the ClinicalTrials.gov and International Clinical Trial Registry Platform public registries. The risk of bias was assessed using the JBI Critical Appraisal tools for use in systematic reviews. We identified 21 studies (17 published, 4 unpublished clinical trials) involving 471 patients. The studies focused on evaluating the efficacy of BONT-A for major depressive, borderline personality, social anxiety, and bipolar disorders. BONT-A was most commonly injected into the glabellar area, with an average dose ranging between 37.75 U and 44.5 U in published studies and between 32.7 U and 41.3 U in unpublished trials. The results indicated significant symptom reductions across all the studied psychiatric conditions, with mild adverse effects. Thus, BONT-A appears to be safe and well-tolerated for psychiatric disorders of negative affectivity. However, despite the clinical focus, there was a noted shortage of biomarker-related assessments. Future studies should focus on pursuing mechanistic explorations of BONT-A effects at the neurobiological level.

Post-stroke spasticity is a common complication that limits the functional performance of patients. Botulinum toxin (BTx) is an effective treatment for spasticity. Numerous researchers have applied extracorporeal shock wave therapy (ESWT) to address post-stroke spasticity, yielding positive clinical outcomes. We aimed to clarify the add-on effects of ESWT on BTx therapy for spasticity in patients with post-stroke. Sixteen eligible patients with upper extremity spasticity after stroke were recruited for this study. They were randomized to either a BTx with focused ESWT treatment group or a BTx alone group. Spasticity, measured using the modified Ashworth score (MAS) and modified Tardieu scale (MTS), showed statistically significant improvements in the elbow and wrist flexor muscles in both BTx + ESWT group and BTx alone groups. However, no significant differences were observed between the two groups with time flow. The BTx + ESWT group showed significantly decreased MAS of the finger flexors at follow-up and increased R1 (MTS) of the finger flexors at 3 weeks after treatment, which was not observed in the BTx alone group. This is the first study to identify the add-on effect of ESWT on BTx injections to improve post-stroke upper limb spasticity.

Background: After significant weight loss, the abdominal skin can become permanently stretched, resulting in stretch marks, laxity, and thinning of the dermis. For many patients, surgical methods such as abdominoplasty are too risky due to the potential for complications, the lengthy recovery period, and the high cost. Objective: The purpose of this pilot study was to use microfocused ultrasound, calcium hydroxyapatite, and Incobotulinum toxin A to improve the appearance of patients who were suffering from abdominal skin laxity after heavy weight loss. The combination of these treatments can provide comprehensive results with minimal downtime and lower risk compared to traditional surgical procedures. Methods: Our team treated four female Chinese patients with microfocused ultrasound, diluted calcium hydroxylapatite, and Incobotulinum toxin A with different combinations, respectively. The first and second cases were only treated with 810 shots of microfocused ultrasound. The third case received 850 shots of microfocused ultrasound plus 5 mL of diluted calcium hydroxylapatite and 50 units of Incobotulinum toxin A on the left abdominal skin, and the fourth case was treated with 900 shots of microfocused ultrasound plus 5 mL of diluted calcium hydroxylapatite and 10 units of Incobotulinum toxin A on the left abdominal skin. All four patients received a single treatment session. Clinical photographs were taken before each treatment, and two individual blinded investigators were asked to assess photographs taken after 4 weeks and compare them with the pretreatment photos. Results: All four cases showed an overall clinical improvement, with the third and fourth cases demonstrating more significant skin tightening based on photographic analysis. The data indicate that the inclusion of calcium hydroxylapatite and Incobotulinum toxin A in microfocused ultrasound treatment yields superior results for abdominal rejuvenation. Conclusions: Abdominal skin laxity can be treated with a triple therapy combining microfocused ultrasound, diluted calcium hydroxylapatite, and Incobotulinum toxin A.

A case of a purely eccrine nevus in an adolescent patient presenting with focal hyperhidrosis on an area comprising the left forearm and the dorsal aspect of the left hand is described. No clinically evident lesions were identifiable. Dermatopathologic findings were subtle, showing only a slight increase in the number of eccrine glands. Clinicopathological correlation was paramount to achieve the diagnosis.

Temporomandibular disorders (TMD) are complex pathologies responsible for chronic orofacial pain. Intramuscular injection of botulinum toxin A (BoNT/A) has shown effectiveness in knee and shoulder osteoarthritis, as well as in some TMDs such as masticatory myofascial pain, but its use remains controversial. This study aimed to evaluate the effect of intra-articular BoNT/A injection in an animal model of temporomandibular joint osteoarthritis. A rat model of temporomandibular osteoarthritis was used to compare the effects of intra-articular injection of BoNT/A, placebo (saline), and hyaluronic acid (HA). Efficacy was compared by pain assessment (head withdrawal test), histological analysis, and imaging performed in each group at different time points until day 30. Compared with the rats receiving placebo, those receiving intra-articular BoNT/A and HA had a significant decrease in pain at day 14. The analgesic effect of BoNT/A was evident as early as day 7, and lasted until day 21. Histological and radiographic analyses showed decrease in joint inflammation in the BoNT/A and HA groups. The osteoarthritis histological score at day 30 was significantly lower in the BoNT/A group than in the other two groups (p = 0.016). Intra-articular injection of BoNT/A appeared to reduce pain and inflammation in experimentally induced temporomandibular osteoarthritis in rats.

Lower urinary tract symptoms (LUTS), such as urgency, urinary incontinence, and/or difficulty voiding, hamper the quality of life (QoL) of patients with spinal cord injury (SCI). If not managed adequately, urological complications, such as urinary tract infection or renal function deterioration, may further deteriorate the patient’s QoL. Botulinum toxin A (BoNT-A) injection within the detrusor muscle or urethral sphincter yields satisfactory therapeutic effects for treating urinary incontinence or facilitating efficient voiding; however, adverse effects inevitably follow its therapeutic efficacy. It is important to weigh the merits and demerits of BoNT-A injection for LUTS and provide an optimal management strategy for SCI patients. This paper summarizes different aspects of the application of BoNT-A injection for lower urinary tract dysfunctions in SCI patients and provides an overview of the benefits and drawbacks of this treatment.

Intravesical botulinum toxin type A (BoNT-A) injection has been recognized as the standard treatment for refractory overactive bladder (OAB). However, its therapeutic efficacy and safety have not been thoroughly reviewed in elderly patients. This study aims to provide treatment outcomes for patients aged ≥75 years, and to identify factors associated with unfavorable outcomes. Patients receiving intradetrusor injections of 100 U onabotulinumtoxinA for refractory OAB between 2011 and 2021 were retrospectively reviewed. Urodynamic parameters, underlying comorbidities, subjective success, and unfavorable outcomes were assessed. A total of 192 patients were included, and 65 of them were classified into the elderly group. For the elderly group, 60.0% experienced subjective dryness, and 84.6% remained subjective success at 6 months after the injections. The prevalence rates of common unfavorable outcomes, including urinary tract infections, large post-void residual urine volume, and urinary retention, were 9.2%, 27.7%, and 12.3%, respectively. Multivariate analysis revealed that female, baseline urodynamic parameters, and diabetes mellitus were associated with unfavorable outcomes in the elderly group. Intravesical BoNT-A injections provide comparable therapeutic efficacy and safety concerns in elderly patients with refractory OAB. A thorough consultation for treatment benefits and possible adverse events is mandatory before the procedure.

DaxibotulinumtoxinA for Injection (DAXI) is a novel botulinum toxin type A product containing daxibotulinumtoxinA with a stabilizing excipient peptide (RTP004). DAXI immunogenicity was assessed in three phase 3 glabellar line studies (two placebo-controlled, single-dose studies and an open-label repeat-dose safety study). Binding antibodies to daxibotulinumtoxinA and RTP004 were detected by validated ELISAs. Samples positive for daxibotulinumtoxinA-binding antibodies were evaluated further for titer and neutralizing antibodies by mouse protection assay. Overall, 2786 subjects received DAXI and 2823 subjects were exposed to RTP004 as DAXI (n = 2786) or placebo (n = 37). Treatment-related anti-daxibotulinumtoxinA binding antibodies were detected in 21 of 2737 evaluable subjects (0.8%). No subject developed neutralizing antibodies. Treatment-related anti-RTP004 binding antibodies were detected in 35 (1.3%) of 2772 evaluable subjects. Binding antibodies were generally transient, of low titer (

Background: Botulinum toxin type A is widely utilized for both therapeutic and aesthetic purposes, yet concerns regarding its immunogenicity have raised issues related to treatment failure and adverse reactions., Objective: This review aims to evaluate the immunogenicity of commercially available botulinum toxin type A products across various clinical indications and identify the risk factors associated with antibody formation., Methods: A comprehensive search of electronic databases was conducted to find studies that investigated the immunogenicity of botulinum toxin type A in patients treated for different conditions. The studies were classified based on the Oxford Center for Evidence-Based Medicine's evidence hierarchy., Results: The overall incidence of neutralizing antibody formation with botulinum toxin type A treatment is relatively low. However, it varies depending on the indication and is influenced by factors such as the frequency of injections and the cumulative dose. The total cumulative dose and the number of treatment cycles are critical factors in determining the risk of developing antibodies against botulinum toxin type A., Conclusion: This literature review highlights that the immunogenicity of botulinum toxin type A products differs across indications, with repeated injections posing a significant risk for the formation of neutralizing antibodies. The findings underscore the need for further research to better understand antibody formation mechanisms and to develop strategies that minimize their impact on treatment efficacy.

To describe the need and effectiveness of acute and preventive medications in a series of 100 consecutive patients referred due to COVID-19-related headaches. Patients were aged 48.0 (standard deviation (SD): 12.4), 84% were female, and 56% had a prior history of headache. The most common headache phenotype was holocranial (63%), frontal (48%), pressing (75%), of moderate intensity (7 out of 10), and accompanied by photophobia (58%). Acute medication was required by 93%, with paracetamol (46%) being the most frequently used drug, followed by ibuprofen (44%). The drugs with the highest proportion of a 2 h pain-freedom response were dexketoprofen (58.8%), triptans (57.7%), and ibuprofen (54.3%). Preventive treatment was required by 75% of patients. The most frequently used drugs were amitriptyline (66%), anesthetic blockades (18%), and onabotulinumtoxinA (11%). The drugs with the highest 50% responder rate were amitriptyline (45.5%), mirtazapine (50%), and anesthetic blockades (38.9%). The highest 75% responder rate was experienced following onabotulinumtoxinA (18.2%). In conclusion, most patients required acute medication, with triptans and non-steroidal anti-inflammatory drugs achieving the best responses. Three-quarters of patients required preventive medication. The most frequently used drug was amitriptyline, which obtained the best results. In some treatment-resistant patients, anesthetic blockades and onabotulinumtoxinA were also beneficial.

There is no gold-standard treatment for idiopathic toe walking (ITW). Some previous evidence suggested that botulinum neurotoxin-A injection might improve ITW. This is a single-center retrospective study on children with ITW treated with incobotulinumtoxinA injection in the gastrocnemius medialis/lateralis muscles. We screened the charts of 97 ITW children treated with incobotulinumtoxinA (January 2019–December 2021), and the data of 28 of them, who satisfied the inclusion/exclusion criteria, were analyzed. The maximal passive ankle dorsiflexion (knee extended) was assessed at three time points, i.e., immediately before incobotulinumtoxinA injection (T0), after incobotulinumtoxinA injection during the timeframe of its effect (T1), and at follow-up, when the effect was expected to disappear (T2). The maximal passive ankle dorsiflexion was improved by incobotulinumtoxinA injection, and the effect lasted up to 6 months in some children. No adverse effects were reported to incobotulinumtoxinA injections. The treatment with incobotulinumtoxinA might improve the maximal passive ankle dorsiflexion and is safe and well-tolerated in ITW with a longer-than-expected effect in comparison to cerebral palsy. These results may offer ground to future randomized controlled trials and studies assessing the effect of BoNT-A in combination with other non-invasive approaches and exercise programs in children with ITW.

Disabling limb spasticity can result from stroke, traumatic brain injury or other disorders causing upper motor neuron lesions such as multiple sclerosis. Clinical studies have shown that abobotulinumtoxinA (AboBoNT-A) therapy reduces upper and lower limb spasticity in adults. However, physicians may administer potentially inadequate doses, given the lack of consensus on adjusting dose according to muscle volume, the wide dose ranges in the summary of product characteristics or cited in the published literature, and/or the high quantity of toxin available for injection. Against this background, a systematic literature review based on searches of MEDLINE and Embase (via Ovid SP) and three relevant conferences (2018 to 2020) was conducted in November 2020 to examine AboBoNT-A doses given to adults for upper or lower limb muscles affected by spasticity of any etiology in clinical and real-world evidence studies. From the 1781 unique records identified from the electronic databases and conference proceedings screened, 49 unique studies represented across 56 publications (53 full-text articles, 3 conference abstracts) were eligible for inclusion. Evidence from these studies suggested that AboBoNT-A dose given per muscle in clinical practice varies considerably, with only a slight trend toward a relationship between dose and muscle volume. Expert-based consensus is needed to inform recommendations for standardizing AboBoNT-A treatment initiation doses based on muscle volume.

Background/Objectives : To determine whether a sitting position with the femoral heads centered into the acetabulum is more effective than the usual sitting position in preventing migration percentage progression in non-ambulatory children with bilateral cerebral palsy. Methods : This was a multicenter, randomized controlled trial., Inclusion Criteria: spastic or dyskinetic cerebral palsy, Gross Motor Function Classification System level IV-V, age 1-6 years, migration percentage <41%, and informed consent., Exclusion Criteria: contractures affecting the hip, anterior luxation, previous hip surgery, and lumbar scoliosis. The treatment group sat with their hips significantly abducted to reduce the head into the acetabulum in a customized system for at least five hours/day for two years. Controls sat with the pelvis and lower limbs aligned but the hips less abducted in an adaptive seating system. The primary outcome was migration percentage (MP) progression. Health-related quality of life and family satisfaction were among the secondary outcomes. The study was approved by the local ethics board and conducted in accordance with CONSORT reporting guidelines., Clinicaltrials: gov ID: NCT04603625., Results: Overall median MP progression was 1.6 after the first year and 2.5 after the second year. No significant differences were observed between the groups. MP exceeded 40% and 50% in 1.8% and 0% of the experimental group and 5.4% and 3.6% of controls in years 1 and 2, respectively. Both groups expressed satisfaction with the postural system and stable health-related quality of life. Conclusions : MP remained stable over the two-year period in both groups. Considering outliers which progressed over 50%, a more protective trend of the hip-centering sitting approach emerged, but this needs to be confirmed in a final, larger dataset.

Improvements in Botulinum toxin type-A (BoNT-A) aesthetic treatments have been jeopardized by the simplistic statement: “BoNT-A treats wrinkles”. BoNT-A monotherapy relating to wrinkles is, at least, questionable. The BoNT-A mechanism of action is presynaptic cholinergic nerve terminals blockage, causing paralysis and subsequent muscle atrophy. Understanding the real BoNT-A mechanism of action clarifies misconceptions that impact the way scientific productions on the subject are designed, the way aesthetics treatments are proposed, and how limited the results are when the focus is only on wrinkle softening. We designed a systematic review on BoNT-A and muscle atrophy that could enlighten new approaches for aesthetics purposes. A systematic review, targeting articles investigating BoNT-A injection and its correlation to muscle atrophy in animals or humans, filtered 30 publications released before 15 May 2020 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Histologic analysis and histochemistry showed muscle atrophy with fibrosis, necrosis, and an increase in the number of perimysial fat cells in animal and human models; this was also confirmed by imaging studies. A significant muscle balance reduction of 18% to 60% after single or seriated BoNT-A injections were observed in 9 out of 10 animal studies. Genetic alterations related to muscle atrophy were analyzed by five studies and showed how much impact a single BoNT-A injection can cause on a molecular basis. Seriated or single BoNT-A muscle injections can cause real muscle atrophy on a short or long-term basis, in animal models and in humans. Theoretically, muscular architecture reprogramming is a possible new approach in aesthetics.

Over the past 30 years, botulinum toxin (BoNT) has seen an ever-expanding use in disorders afflicting the nervous system [...]

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

Several studies have investigated the effect of botulinum toxin A (BoNT-A) for managing chronic musculoskeletal pain, bringing contrasting results to the forefront. Thus far, however, there has been no synthesis of evidence on the effect of BoNT-A as an adjunctive treatment within a multimodal approach. Hence, Medline via PubMed, EMBASE, and the Cochrane Library-CENTRAL were searched until November 2020 for randomised controlled trials (RCTs) that investigated the use of BoNT-A as an adjunctive therapy for chronic musculoskeletal pain. The risk of bias (RoB) and the overall quality of the studies were assessed through RoB 2.0 and the GRADE approach, respectively. Meta-analysis was conducted to analyse the pooled results of the six included RCTs. Four were at a low RoB, while two were at a high RoB. The meta-analysis showed that BoNT-A as an adjunctive therapy did not significantly decrease pain compared to the sole use of traditional treatment (SDM −0.89; 95% CI −1.91; 0.12; p = 0.08). Caution should be used when interpreting such results, since the studies displayed very high heterogeneity (I = 94%, p < 0.001). The overall certainty of the evidence was very low. The data retrieved from this systematic review do not support the use of BoNT-A as an adjunctive therapy in treating chronic musculoskeletal pain.

There is no available data on the journey of dystonia patients once referred to a tertiary center to undergo deep brain stimulation (DBS). We hypothesized that some patients might be incorrectly diagnosed while others might decline the procedure or experience significant benefit with switching to a different botulinum neurotoxin (BoNT). This is a single-center, retrospective study of dystonia patients who were referred to the DBS program between January 2014 and December 2018. We collected data on the surgical decision as well as factors influencing this decision. Sixty-seven patients were included (30 males, mean age: 48.3 ± 20.1 years, disease duration: 16.9 ± 15.3 years). Thirty-three (49%) patients underwent DBS. Four (6%) patients were awaiting the procedure while the remaining 30 patients (45%) did not undergo DBS. Reasons for DBS decline were patient refusal (17, 53%), functional dystonia (6, 20%), and successful use of AbobotulinumtoxinA (3, 10%) in patients who had failed other BoNTs. Our study highlights the importance of structured patient education to increase acceptance of DBS, as well as careful patient evaluation, particularly with respect to functional dystonia. Finally, changing BoNT formulation might be beneficial in some patients.

The real-world use of onabotulinumtoxinA and incobotulinumtoxinA for cervical dystonia and blepharospasm treatment was assessed in two separate retrospective studies using identical protocols (TRUDOSE and TRUDOSE II). The studies were conducted in Mexico, Norway, and United Kingdom and designed to evaluate dose utilization of the two botulinum toxins in clinical practice. Eighty-three patients treated with both onabotulinumtoxinA and incobotulinumtoxinA for ≥2 years for each botulinum toxin were included, (52, cervical dystonia; 31, blepharospasm). All patients switched from onabotulinumtoxinA to incobotulinumtoxinA for administrative/financial reasons. A range of dose ratios (incobotulinumtoxinA to onabotulinumtoxinA) was reported; with the majority of dose ratios being >1. The mean dose ratio was >1 regardless of the study site or underlying clinical condition. The inter-injection interval was significantly longer for onabotulinumtoxinA versus incobotulinumtoxinA when assessed for all patients (15.5 vs. 14.3 weeks; p = 0.006), resulting in fewer onabotulinumtoxinA treatments over the study time period. Consistent with product labeling, no single fixed-dose ratio exists between incobotulinumtoxinA and onabotulinumtoxinA. The dosage of each should be individualized based on patient needs and used as per product labeling. These real-world utilization data may have pharmacoeconomic implications.

Early management of spasticity may improve stroke outcome. Botulinum toxin type A (BoNT-A) is recommended treatment for post-stroke spasticity (PSS). However, it is usually administered in the chronic phase of stroke. Our aim was to determine whether the length of time between stroke onset and initial BoNT-A injection has an effect on outcomes after PSS treatment. This multicenter, longitudinal, cohort study included stroke patients (time since onset 90 days, the MAS were higher at 4 and 12 weeks than at 24 weeks compared to those injected ≤90 days since stroke. Our findings suggest that BoNT-A treatment for PSS should be initiated within 3 months after stroke onset in order to obtain a greater reduction in muscle tone at 1 and 3 months afterwards.

Botulinum toxin type A (BoNT-A) represents a first-line treatment for spasticity, a common disabling consequence of many neurological diseases. Electrical stimulation of motor nerve endings has been reported to boost the effect of BoNT-A. To date, a wide range of stimulation protocols has been proposed in the literature. We conducted a systematic review of current literature on the protocols of electrical stimulation to boost the effect of BoNT-A injection in patients with spasticity. A systematic search using the MeSH terms “electric stimulation”, “muscle spasticity” and “botulinum toxins” and strings “electric stimulation [mh] OR electrical stimulation AND muscle spasticity [mh] OR spasticity AND botulinum toxins [mh] OR botulinum toxin type A” was conducted on PubMed, Scopus, PEDro and Cochrane library electronic databases. Full-text articles written in English and published from database inception to March 2021 were included. Data on patient characteristics, electrical stimulation protocols and outcome measures were collected. This systematic review provides a complete overview of current literature on the role of electrical stimulation to boost the effect of BoNT-A injection for spasticity, together with a critical discussion on its rationale based on the neurobiology of BoNT-A uptake.

We aimed to evaluate muscle mass changes after injection of botulinum toxin (BoNT) in children with spastic hemiplegic cerebral palsy (CP). Children aged between 2 and 12 years who were diagnosed with hemiplegic CP with spastic equinus foot were prospectively recruited and administered BoNT in the affected leg. Lean body mass (LBM) of both legs and total limbs was measured by dual-energy X-ray absorptiometry (DXA) preinjection and 4 and 12 weeks after injection. A total of 15 children were enrolled into the study. LBM of both legs and total limbs increased significantly over 12 weeks of growth. The ratio of LBM of the affected leg to total limbs and to the unaffected leg significantly reduced at 4 weeks after injection compared with preinjection but significantly increased at 12 weeks after injection compared with 4 weeks after injection. In conclusion, the muscle mass of the affected leg after BoNT injection in children with hemiplegic spastic CP decreased at 4 weeks after BoNT injection but significantly recovered after 12 weeks after injection.

Background: Complex ventral hernias following laparotomy present a unique challenge in that repair is hindered by the lateral tension of the abdominal wall. A novel approach to overcome this is the “chemical component separation” technique. Here, botulinum toxin A (BTA) is instilled into the muscles of the abdominal wall. This induces flaccid paralysis and effectively reduces tension in the wall, allowing the muscles to be successfully joined in the midline during surgery. We describe a method where a large incisional hernia was repaired using this technique and review the variations in methodology. Case report: A woman in her mid-40s developed a ventral hernia in the setting of a previous laparotomy for a small bowel perforation. Computed tomography (CT) of the abdomen demonstrated an 85 (Width) × 95 mm (Length) ventral hernia containing loops of the bowel. Pre-operative botulinum toxin A administration was arranged at the local interventional radiology department. A total of 100 units of BTA were instilled at four sites into the muscular layers of the abdominal wall under CT-fluoroscopic guidance. She underwent an open incisional hernia repair 4 weeks later, where the contents were reduced and the abdominal wall layers were successfully joined in the midline. There was no clinical evidence of hernia recurrence at 3-months follow-up. Conclusion: Low-dose BTA effectively facilitates the surgical management of large ventral incisional hernias. There is, however, significant variation in the dosage, concentration and anatomical landmarks in which BTA is administered as described in the literature. Further studies are needed to assess and optimise these variables.

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

The purpose of this study was to compare the efficacy of botulinum toxin (BoNT) in masseter muscle reduction depending on the amount of chin deviation. Exploring distinctive effects of BoNT relative to the characteristics of facial asymmetry will aid in planning and predicting treatment outcomes. Sixteen adult volunteers were classified into two groups according to the degree of menton deviation observed in posteroanterior cephalograms. Eight had a menton deviation of 3 mm or more and the other eight had less than 3 mm. A total of 25 Units of BoNT was injected into the unilateral masseter muscle of the prominent side for each participant. Changes in the volume and bulkiest height of the lower face on each side were measured with a 3D laser scan at four time points: before and 4, 8, and 12 weeks after the injection. Two-way mixed ANOVA was employed for analyses. The volume and bulkiest height of the injected side decreased over time in both types of asymmetry, with significant differences at each time point. The reductions in the volume and bulkiest height were significantly greater in subjects without chin deviation. The reductions in the volume and bulkiest height of the lower face using BoNT are more effective for subjects without chin deviation.

Botulinum neurotoxin (BoNT), derived from Clostridium botulinum, has been used therapeutically for focal dystonia, spasticity, and chronic migraine. Its spectrum as a potential treatment for neuropathic pain has grown. Recent opinions on the mechanism behind the antinociceptive effects of BoNT suggest that it inhibits the release of peripheral neurotransmitters and inflammatory mediators from sensory nerves. There is some evidence showing the axonal transport of BoNT, but it remains controversial. The aim of this review is to summarize the experimental and clinical evidence of the antinociceptive effects, mechanisms, and therapeutic applications of BoNT for neuropathic pain conditions, including postherpetic neuralgia, complex regional pain syndrome, and trigeminal neuralgia. The PubMed and OvidSP databases were searched from 1966 to May 2015. We assessed levels of evidence according to the American Academy of Neurology guidelines. Recent studies have suggested that BoNT injection is an effective treatment for postherpetic neuralgia and is likely efficient for trigeminal neuralgia and post-traumatic neuralgia. BoNT could also be effective as a treatment for diabetic neuropathy. It has not been proven to be an effective treatment for occipital neuralgia or complex regional pain syndrome.

(1) Background: The purpose of this study was to determine whether the drooling of adult patients with diverse central nervous system diseases can be treated with botulinum toxin type A. (2) Methods: The Cochrane Library, MEDLINE, and Embase were all searched for studies that fit the inclusion criteria. The patients in the studies had to be adults (>18 years old), and the studies had to be randomized placebo-controlled trials, controlled trials, or prospective studies. Each study had to have enough quantifiable data available for meta-analysis. The primary outcome measure was the Drooling Severity and Frequency Scale (DSFS). (3) Results: The meta-analysis comprised three studies. A statistically significant difference in DSFS score between the treatment and control groups was observed in the meta-analysis, with an overall standardized mean difference of -0.9377 (95% CI, -1.2919 to -0.5836; p < 0.0001). A total of seven studies were ineligible for inclusion in the meta-analysis and were only assessed as qualitative data. All qualitative studies showed a significant reduction in DSFS score a few weeks or months after the injection of botulinum toxin. (4) Conclusions: Botulinum toxin type A is safe and effective as a treatment for drooling in adult patients with central nervous system diseases.

Cell-based biosensors (CBBs) utilize the principles of cell-based assays (CBAs) by employing living cells for detection of different analytes from environment, food, clinical, or other sources. For toxin detection, CBBs are emerging as unique alternatives to other analytical methods. The main advantage of using CBBs for probing biotoxins and toxic agents is that CBBs respond to the toxic exposures in the manner related to actual physiologic responses of the vulnerable subjects. The results obtained from CBBs are based on the toxin-cell interactions, and therefore, reveal functional information (such as mode of action, toxic potency, bioavailability, target tissue or organ, etc.) about the toxin. CBBs incorporate both prokaryotic (bacteria) and eukaryotic (yeast, invertebrate and vertebrate) cells. To create CBB devices, living cells are directly integrated onto the biosensor platform. The sensors report the cellular responses upon exposures to toxins and the resulting cellular signals are transduced by secondary transducers generating optical or electrical signals outputs followed by appropriate read-outs. Examples of the layout and operation of cellular biosensors for detection of selected biotoxins are summarized.