Doses Of Botulinum Toxin Type A Research Articles

Effects of botulinum toxin type A in patients with painful temporomandibular joint disorders: A systematic review and meta-analysis

Objective: To assess the therapeutic efficacy of botulinum toxin type A (BTX-A) for managing myofascial pain related to temporomandibular disorders (TMDs). Methods: This study was conducted according to the PRISMA 2020 statement guidelines. The PubMed, Embase, and Cochrane Library databases were searched. Only randomized controlled trials (RCTs) were included. The primary outcome was pain score on the visual analogue scale (VAS), and the secondary outcomes were maximum mouth opening (MMO) and adverse effects. The Cochrane risk of bias tool was used to assess risk bias. A meta-analysis of studies with the same interventions, controls, assessment methods and follow-up durations was performed. Results: A total of 519 studies were retrieved, of which 20 RCTs were included in the qualitative analysis and 6 were included in the meta-analysis. The results showed that, compared with placebo, BTX-A injection was more effective at relieving myofascial pain, and its effect was similar to that of conventional methods. However, there was no difference in MMO between the two groups. After study assessment with the RoB 2.0 tool, six studies showed a low risk of bias, 13 studies showed some concerns regarding the reported results, and only one study showed a high risk of bias. Adverse effects of BTX-A injection were observed in four studies. Conclusions: In conclusion, BTX-A is effective at relieving pain in TMD patients but does not improve mouth opening. To minimize adverse effects, we recommend a low dose of BTX-A for TMD patients who do not experience complete pain relief from conservative treatments.

Optimizing Botulinum Toxin A Administration for Forehead Wrinkles: Introducing the Lines and Dots (LADs) Technique and a Predictive Dosage Model.

This study introduces the Lines and Dots (LADs) technique, a new approach for administering botulinum toxin type A (BoNT-A) in treating forehead wrinkles. (1) Background: BoNT-A application patterns in the forehead often rely solely on the anatomy of the frontalis muscle. The LADs technique proposes a combination of anatomical features with nerve pathways. (2) Methods: The technique employed a grid system aligned with the supraorbital and supratrochlear nerve pathways and used an electronic acupuncture pen for validation. This study analyzed treatment outcomes for efficacy and safety and proposed a predictive model for BoNT-A dosage. (3) Results: LADs was associated with a high satisfaction rate and low side effect incidence. The predictive model followed BoNT-A Units=0.322×Muscle Pattern Code+1.282×Line Type Code+2.905×Severity Pre-Treatment+3.947. (4) Conclusions: The LADs technique offers an alternative approach to treating forehead wrinkles, optimizing efficacy while minimizing the BoNT-A dose required.

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

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. To assess the efficacy, safety and optimal dose of BTX-A for treating TMD. 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. 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. 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.

A Multicenter Phase II Study Evaluating the Safety and Efficacy of Botulax in Asian Patients with Benign Masseteric Hypertrophy.

Benign masseteric hypertrophy (BMH) is a condition in which the thickness of the masseter muscle is increased, resulting in jawline prominence with an undesirable cosmetic appearance. Botulinum toxin type A (BTA) injection is a promising treatment option, but its effective dose remains debated. Adults older than 19 diagnosed with BMH through visual examination and palpation related to a masseter muscle prominence were selected, and 80 patients were randomly assigned into five groups (placebo group and four groups with different doses of BTA: 24 U, 48 U, 72 U, or 96 U, on both sides of the jaw) and treated with placebo or BTA once at their baseline visit. During each follow-up, the treatment efficacy was evaluated with ultrasound examination of the masseter muscle, three-dimensional facial contour analysis, visual evaluation by the investigator, and patient satisfaction evaluation. The mean age of the 80 patients was 42.7 ± 9.98 years; 68.75% were women. The mean change in masseter muscle thickness during the maximum clenching state after 12 weeks of drug administration compared with baseline in the 24-U, 48-U, 72-U, and 96-U groups were -2.33 ± 0.41 mm, -3.35 ± 0.42 mm, -2.86 ± 0.42 mm, and -3.79 ± 0.42 mm, respectively. All treatment groups showed a statistically significant decrease compared with placebo. Regarding subjective satisfaction, all treatment groups, except the 24-U group at 4 weeks, showed higher satisfaction than the placebo group during all visits. No significant adverse events were noted. BTA administration of at least 48 U for BMH is more cost-effective than high-dose units and has a low risk of side effects. Therapeutic, II.

Botulinum toxin-A injection improves motor recovery in patients with stroke

Aim: Spasticity that occurs after a stroke may contribute to disability. Botulinum toxin type-A (BTX-A) injections are commonly used to manage spasticity. This study sought to determine the effectiveness of BTX-A injections on spasticity and motor recovery in patients with stroke. Materials and Methods: Twenty-five patients with stroke scheduled for BTX-A injection for spasticity were included in the study. The patients were analyzed in two groups: upper limb and lower limb group. A single dose of BTX-A was applied to the patients. Before, 2, and 12 weeks after BTX-A injections, motor function was assessed using Brunnstrom recovery stages, and spasticity was evaluated according to Modified Ashworth Scale (MAS). The lower limb group additionally underwent the Functional Ambulation Classification (FAC) and 10-meter walking test. Results: Mean age of patients was 54.96 ± 12.84 years. Eighteen patients were enrolled in the upper limb group and 23 in the lower limb group. Clinical evaluation of the upper limb group two weeks after injections demonstrated a significant decrease in shoulder adductor muscle MAS, elbow, wrist, and finger flexor muscles MAS, and a significant improvement in Brunnstrom recovery stages for the upper limb and hand (p&lt;0.05). At week 12, spasticity decreased only for the shoulder adductor muscles. In the lower limb group, clinical evaluation at week 2 showed a decrease in the knee extensor and toe flexor muscles MAS. Assessment of the patients at week 12 found a significant improvement in Brunnstrom recovery stage for the lower limbs (p&lt;0.05). There was no statistically significant recovery in the FAC and 10-meter walking test (p&gt;0.05). Conclusion: This study supports that BTX-A injections are effective for improving spasticity and motor function in patients with stroke.

Cellular Mechanisms Mediating the Antinociceptive Effect of Botulinum Toxin A in a Rodent Model of Trigeminal Irritation by a Foreign Body

Although numerous studies have described botulinum toxin type A (BTX-A) efficacy against trigeminal neuralgia (TN), the underlying cellular mechanisms remain unclear. We have investigated cellular mechanisms that mediate the antinociceptive effect of BTX-A in a rodent model of TN produced by compression of the trigeminal nerve root (TNR). Anesthetized male Sprague-Dawley rats were fixed in a stereotaxic instrument and compression of the TNR was then achieved with a 4% agar solution. This model produced a significant mechanical allodynia and increased the expression of hypoxia-inducible factor (HIF)-1α and cytokines levels including interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in the trigeminal ganglion (TG) by postoperative day (POD) 7. Single or double treatments with a high BTX-A dose (3 U/kg) led to significantly prolonged antinociceptive effects. Furthermore, a single treatment with BTX-A (3 U/kg) significantly suppressed the upregulation of HIF-1α expression and IL-1β, IL-6, and TNF-α concentrations in the TG. Intraganglionic injection of PX-12, a HIF-1α inhibitor, led to significant anti-allodynic effects and lowered the IL-1β, IL-6, and TNF-α levels in the TG. These findings indicate that the antinociceptive effect of BTX-A is mediated via HIF-1α associated cytokines modulation in the TG and is therefore a potentially relevant treatment strategy for TN. PerspectiveThe antinociceptive properties of BTX-A in a rat model of trigeminal neuralgia are mediated through the regulation of the HIF-1α associated cytokine pathway in the trigeminal ganglion. BTX-A is therefore a potentially effective treatment strategy for trigeminal neuralgia.

Effects of Botulinum Toxin Type A on the Psychosocial Features of Myofascial Pain TMD Subjects: A Randomized Controlled Trial.

To determine the effects of botulinum toxin type A (BoNT-A) on the psychosocial features of patients with masticatory myofascial pain (MFP). A total of 100 female subjects diagnosed with MFP were randomly assigned into five groups (n = 20 each): oral appliance (OA); saline solution (SS); and three groups with different doses of BoNT-A. Chronic pain-related disability and depressive and somatic symptoms were evaluated with the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) Axis II instruments at baseline and after 6 months of treatment. Differences in treatment effects within and between groups were compared using chi-square test, and Characteristic Pain Intensity (CPI) was compared using two-way ANOVA. A 5% probability level was considered significant in all tests. Most patients presented low pain-related disability (58%), and 6% presented severely limiting, high pain-related disability. Severe depressive and somatic symptoms were found in 61% and 65% of patients, respectively. In the within-group comparison, BoNT-A and OA significantly improved (P < .001) scores of pain-related disability and depressive and somatic symptoms after 6 months. Only the scores for pain-related disability changed significantly over time in the SS group. In the between-group comparison, BoNT-A and OA significantly improved (P < .05) scores of all variables at the final follow-up when compared to the SS group. No significant difference was found between the BoNT-A and OA groups (P > .05) for all assessed variables over time. BoNT-A was at least as effective as OA in improving pain-related disability and depressive and somatic symptoms in patients with masticatory MFP.

Is low dose of botulinum toxin effective in controlling chronic pain in sleep bruxism, awake bruxism, and temporomandibular disorder?

ABSTRACT Objective To evaluate the effects of low doses of botulinum toxin type A (BoNT-A) to control pain in patients with sleep bruxism (SB), awake bruxism (AB), and temporomandibular disorder (TMD) during 180 days. Methods Overall sample of thirty-five patients with chronic pain related to TMD, SB, and AB received a single dose of 20 U of BoNT-A in masseter and temporalis muscles. The pain was assessed with a visual analog scale (VAS) before and after 15, 30, 60, 90, and 180 days of the application. Results The three clinical conditions experienced decrease in pain after 15 days of treatment (p < 0.0001); the maximum pain relief persisted for up to 90 days after BoNT-A application in patients with SB and AB and 15 days for patients with TMD. Conclusion A low dose of BoNT-A may be effective for controlling chronic pain related to SB and AB, but TMD pain reduction was short-lived.

Safety and efficacy of botulinum toxin type A in preventing and treating scars in animal models: A systematic review and meta-analysis.

Previous studies have used botulinum toxin type A (BTXA) to improve postoperative and hypertrophic scars; however, there is lack of detailed verification on the safety and effectiveness of this approach. This study aimed to evaluate the therapeutic effect of BTXA on postoperative hypertrophic scars and its influence on cytokine expression in animal models. A computerised search of different databases was performed, including PubMed, Web of Science, Scopus, Cochrane, Embase, CNKI, and Wanfang, up to 10 March 2021. A meta‐analysis was performed using R 4.0.0 based on hypertrophic index, epithelialisation time, wound area, and vascular endothelial growth factor (VEGF) expression. Eleven studies were included. The meta‐analysis showed a significant difference in hypertrophic index (standardised mean difference [SMD] = −2.63, 95% confidence interval [CI]: −3.50 to −1.76, P < .01), wound area (SMD = −0.54, 95% CI: −1.24 to 0.16, P < .01), and VEGF expression (SMD = −2.56, 95% CI: −3.50 to −1.62, P < .01). This study shows that BTXA is safe and effective in preventing and treating scar hypertrophy in animal models, but excessive doses of BTXA and BTXA to treat large areas should be avoided.

The effect of botulinum toxin injection dose on the appearance of surgical scar

Early postoperative injection of botulinum toxin type A (BTxA) can reduce surgical scar hypertrophy. BTxA injection at different time points is associated with different levels of efficacy, but the efficacy of different doses of BTxA for scar management has not investigated. The purpose of this study was to investigate the effect of different doses of BTxA administered early after surgery on scar improvement through a split-scar experiment. The study included 22 patients who underwent surgery between September 2019 and October 2020. High- and low-dose BTxA was randomly administered into each half of the surgical wound closure immediately after surgery. One half of the incision was injected with a low dose (4 U) of BTxA, and the other half was injected with a high dose (8 U). The scars were then evaluated at postoperative 6 months using the modified Stony Brook Scar Evaluation Scale (mSBSES), and patient satisfaction was evaluated using the Visual Analogue Scale (VAS). The occurrence of complications or adverse events was also recorded. Twenty patients completed the study and were analyzed. Compared with the low-dose sides, the high-dose sides had significantly better mSBSES scores and significantly higher VAS scores (p < 0.01, respectively). No serious adverse reactions or post-injection complications were observed. Immediately after the operation, high-dose BTxA (that is within the therapeutic range) injection improved the appearance of postoperative scar more than low-dose injection.

Botulinum toxin type a intralesional monotherapy for treating human hypertrophic scar in a dose-dependent manner: In an animal model

The effect of Botulinum toxin type A (BTX-A) in treating or preventing a hypertrophic scar (HS) had been reported in clinical studies. However, the dose-effect relationship remains unclear. To study the dose-effect relationship of BTX-A intralesional monotherapy treating human HS. Six HS tissues were collected from six patients. Each tissue was segmented into 24 specimens and split into four groups: negative control (group A), 0.5U BTX-A (group B), 1U BTX-A (group C), and 2U BTX-A (group D). Six nude mice, each was prepared by implanting four specimens (one from each group) into the back for a total of 24 specimens. The process mentioned above were repeated six times. A re-entry operation was performed to obtain the specimens after 8 weeks. The weight of HS, the expression of decorin and TGF-β1, the proliferation, and migration ability of hypertrophic scar fibroblasts (HSFBs) were compared among groups. The weight of HS, the expression of decorin and TGF-β1, the proliferation, and migration ability of HSFBs showed significant differences in groups C and D as compared to group A; there has been no statistical significance in group B. BTX-A showed significant therapeutic efficacy when compared with the negative control group in a dose-dependent manner. BTX-A can reduce the weight of HS, upregulate the expression of decorin, downregulate the expression of TGF-β1, and inhibit HSFBs proliferation and migration ability. This study indicates that BTX-A intralesional monotherapy treating HS should reach a threshold dose to achieve an effective treatment, and a high dose of BTX-A is more effective than a low dose.

Botulinum toxin type A versus anticholinergics for cervical dystonia.

This is an update of a Cochrane Review first published in 2005. Cervical dystonia is the most common form of focal dystonia and is a highly disabling movement disorder, characterised by involuntary, usually painful, head posturing. Currently, botulinum toxin type A (BtA) is considered the first line therapy for this condition. Before BtA, anticholinergics were the most widely accepted treatment. To compare the efficacy, safety, and tolerability of BtA versus anticholinergic drugs in adults with cervical dystonia. We searched the Cochrane Movement Disorders' Trials Register to June 2003, screened reference lists of articles and conference proceedings to September 2018, and searched CENTRAL, MEDLINE, and Embase, with no language restrictions, to July 2020. Double-blind, parallel, randomised trials (RCTs) of BtA versus anticholinergic drugs in adults with cervical dystonia. Two review authors independently assessed records, selected included studies, extracted data using a paper pro forma, and evaluated the risk of bias and quality of the evidence. We resolved disagreements by consensus or by consulting a third review author. If enough data had been available, we were to perform meta-analyses using a random-effects model for the comparison of BtA versus anticholinergic drugs to estimate pooled effects and corresponding 95% confidence intervals (95% CI). The primary efficacy outcome was improvement in cervical dystonia-specific impairment. The primary safety outcome was the proportion of participants with any adverse event. We included one RCT of moderate overall risk of bias (as multiple domains were at unclear risk of bias), which included 66 BtA-naive participants with cervical dystonia. Two doses of BtA (Dysport; week 0 and 8; mean dose 262 to 292 U) were compared with daily trihexyphenidyl (up to 24 mg daily). The trial was sponsored by the BtA producer. BtA reduced cervical dystonia severity by an average of 2.5 points (95% CI 0.68 to 4.32) on the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) severity subscale 12 weeks after injection, compared to trihexyphenidyl. More participants reported adverse events in the trihexyphenidyl treatment group (76 events), compared with the BtA group (31 events); however, the difference in dropouts due to adverse events was inconclusive between groups. There was a decreased risk of dry mouth, and memory problems with BtA, but the differences were inconclusive between groups for the other reported side effects (blurred vision, dizziness, depression, fatigue, pain at injection site, dysphagia, and neck weakness). We found very low-certainty evidence that BtA is more effective, better tolerated, and safer than trihexyphenidyl. We found no information on a dose-response relationship with BtA, differences between BtA formulations or different anticholinergics, the utility of electromyography-guided injections, or the duration of treatment effect.

Hemifacial spasm through the last three decades: From etiology to efficacy and safety of long-term botulinum toxin treatment

BackgroundHemifacial spasm (HFS) is an uncommon movement disorder characterized by involuntary contractions of muscles innervated by the facial nerve. The aim of this study is to analyze the etiology of HFS as well as the efficacy and safety of long-term botulinum toxin type A (BTX-A) treatment. MethodsRetrospective study including 125 patients with HFS treated with BTX-A from 1993 to 2019. Demographic and etiological variables as well as doses, number of sessions of BTX-A, infiltrated muscles, therapeutic response according to Patient Global Impression of Change Scale (PGIC-S), side effects and adjuvant treatments were analyzed. In addition, these variables were compared according to the etiology (idiopathic versus secondary). Results92 patients (73.6%) were women and the mean age at diagnosis was 58.63 years (SD 15.4). The etiology was idiopathic in 79 patients (63.2%), 17.6% were secondary to Bell’s palsy, 14.4% to vascular compression and 2.4% to tumors. A higher total dose per session was observed in the secondary group. PGIC-S showed a good response in 96% of cases. 16 patients (12.8%) required pharmacological concomitant treatment. 59 patients (47.2%) developed side effects. Transient eyelid ptosis and facial weakness were the most common. ConclusionsThe structural origin of a significant number of cases of HFS makes essential to complete an etiological diagnosis in all patients. In addition, the existence of a secondary cause could be associated with greater doses of BTX-A to achieve a good response. Regardless the etiology, long-term treatment with BTX-A in HFS is safe and effective.

Outcomes of a regional variant of botulinum toxin type A in the treatment of essential blepharospasm and hemifacial spasms: A retrospective study.

Purpose:The aim of this study was to report the outcomes of a regional variant of botulinum toxin type A (BtA) in essential blepharospasm and hemifacial spasm.Methods:The medical records of all patients with facial dystonias, who received at least one dose of BtA between May 2016 and April 2017 were retrospectively evaluated. The pre- and post-injection severity of symptoms, graded using the Jankovic rating system for essential blepharospasm and the Samsung Medical Center grading system for hemifacial spasm, the complications after each sitting, and the mean symptom-free interval were recorded. A correlation analysis was done to identify factors associated with longer symptom-free intervals. A P value < 0.05 was considered statistically significant.Results:The mean age at presentation was 56.62 ± 10.56 years. The mean duration of follow-up was 1.86 ± 2.06 years. The modal disease severity reduced from 5 to 0 in essential blepharospasm and from 2 to 0 in hemifacial spasm a week after injection of botulinum toxin. The mean symptom-free intervals with doses of 20, 22.5, 25, 30, and 50 units were 102.1 ± 44.7, 132.4 ± 35.3, 147.2 ± 61.6, 124.4 ± 55.1, and 142.4 ± 59.7 days, respectively. The commonest complication was lagophthalmos (26.3%; n = 20). Injections for primary dystonias were associated with longer disease-free intervals than those for secondary dystonias (P = 0.02). In nine sittings, the dose was increased for increased severity or presumed resistance, which resulted in a significant increase in the symptom-free interval (P = 0.004) without an increased incidence of complications (P = 0.48).Conclusion:BtA is safe and effective in the treatment of facial dystonias. The drug is more efficacious for primary facial dystonias.

Botulinum toxin type A therapy for cervical dystonia.

This is an update of a Cochrane Review first published in 2005. Cervical dystonia is the most common form of focal dystonia, and is a highly disabling movement disorder, characterised by involuntary, usually painful, head posturing. Currently, botulinum toxin type A (BtA) is considered the first line therapy for this condition. To compare the efficacy, safety, and tolerability of BtA versus placebo, in people with cervical dystonia. We searched Cochrane Movement Disorders' Trials Register, CENTRAL, MEDLINE, Embase, reference lists of articles, and conference proceedings in July 2020. All elements of the search, with no language restrictions, were last run in July 2020. Double-blind, parallel, randomised, placebo-controlled trials (RCTs) of BtA versus placebo in adults with cervical dystonia. Two review authors independently assessed records, selected included studies, extracted data using a paper pro forma, and evaluated the risk of bias. We resolved disagreements by consensus or by consulting a third review author. We performed meta-analyses using a random-effects model, for the comparison of BtA versus placebo, to estimate pooled effects and corresponding 95% confidence intervals (95% CI). We performed preplanned subgroup analyses according to BtA dose used, the BtA formulation used, and the use (or not) of guidance for BtA injections. The primary efficacy outcome was improvement in cervical dystonia-specific impairment. The primary safety outcome was the proportion of participants with any adverse event. We included nine RCTs, with moderate, overall risk of bias, that included 1144 participants with cervical dystonia. Seven studies excluded participants with poorer responses to BtA treatment, therefore, including an enriched population with a higher probability of benefiting from this therapy. Only one trial was independently funded. All RCTs evaluated the effect of a single BtA treatment session, using doses from 150 U to 500 U of onabotulinumtoxinA (Botox), 120 U to 240 U of incobotulinumtoxinA (Xeomin), and 250 U to 1000 U of abobotulinumtoxinA (Dysport). BtA resulted in a moderate to large improvement from the participant's baseline clinical status, assessed by the investigators, with a mean reduction of 8.09 points in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS total score) at week four after injection (95% CI 6.22 to 9.96; I² = 0%) compared to placebo. This corresponded, on average, to a 18.4% improvement from baseline. The mean difference (MD) in TWSTRS pain subscore at week four was 2.11 (95% CI 1.38 to 2.83; I² = 0%) compared to placebo. Overall, both participants and clinicians reported an improvement of subjective clinical status. It was unclear if dropouts due to adverse events differed (risk ratio (RR) 2.51; 95% CI 0.42 to 14.94; I² = 0%) However, BtA treatment increased the risk of experiencing an adverse event (R) 1.23; 95% CI 1.05 to 1.43; I² = 28%). Neck weakness (14%; RR 3.40; 95% CI 1.19 to 9.71; I² = 15%), dysphagia (11%; RR 3.19; 95% CI 1.79 to 5.70; I² = 0%), and diffuse weakness or tiredness (8%; RR 1.80; 95% CI 1.10 to 2.95; I² = 0%) were the most common treatment-related adverse events. Treatment with BtA resulted in a decreased risk of dropouts. We have moderate certainty in the evidence across all of the aforementioned outcomes, with the exception of subjective assessment and tolerability, in which we have high confidence in the evidence. We found no evidence supporting the existence of a clear dose-response relationship between BtA and improvement in cervical dystonia-specific impairment, a destinction between BtA formulations, or a variation with use of EMG-guided injection for efficacy outcomes. Due to clinical heterogeneity, we did not pool health-related quality of life data, duration of clinical effect, or the development of secondary non-responsiveness. We are moderately certain in the evidence that a single BtA treatment session resulted in a clinically relevant reduction of cervical dystonia-specific impairment, and pain, and highly certain that it is well tolerated, compared with placebo. There is moderate-certainty evidence that people treated with BtA are at an increased risk of developing adverse events, most notably, dysphagia, neckweakness and diffuse weakness or tiredness. There are no data from RCTs evaluating the effectiveness and safety of repeated BtA injection cycles. There is no evidence from RCTs to allow us to draw definitive conclusions on the optimal treatment intervals and doses, the usefulness of guidance techniques for injection, the impact on quality of life, or the duration of treatment effect.

Over 25 Years of Pediatric Botulinum Toxin Treatments: What Have We Learned from Injection Techniques, Doses, Dilutions, and Recovery of Repeated Injections?

Botulinum toxin type A (BTXA) has been used for over 25 years in the management of pediatric lower and upper limb hypertonia, with the first reports in 1993. The most common indication is the injection of the triceps surae muscle for the correction of spastic equinus gait in children with cerebral palsy. The upper limb injection goals include improvements in function, better positioning of the arm, and facilitating the ease of care. Neurotoxin type A is the most widely used serotype in the pediatric population. After being injected into muscle, the release of acetylcholine at cholinergic nerve endings is blocked, and a temporary denervation and atrophy ensues. Targeting the correct muscle close to the neuromuscular junctions is considered essential and localization techniques have developed over time. However, each technique has its own limitations. The role of BTXA is flexible, but limited by the temporary mode of action as a focal spasticity treatment and the restrictions on the total dose deliverable per visit. As a mode of treatment, repeated BTXA injections are needed. This literature reviewed BTXA injection techniques, doses and dilutions, the recovery of muscles and the impact of repeated injections, with a focus on the pediatric population. Suggestions for future studies are also discussed.

High Dosage of Botulinum Toxin Type A in Adult Subjects with Spasticity Following Acquired Central Nervous System Damage: Where Are We at?

Spasticity is a common disabling disorder in adult subjects suffering from stroke, brain injury, multiple sclerosis (MS) and spinal cord injury (SCI). Spasticity may be a disabling symptom in people during rehabilitation and botulinum toxin type A (BTX-A) has become the first-line therapy for the local form. High BTX-A doses are often used in clinical practice. Advantages and limitations are debated and the evidence is unclear. Therefore, we analysed the efficacy, safety and evidence for BTX-A high doses. Studies published from January 1989 to February 2020 were retrieved from MEDLINE/PubMed, Embase, Cochrane Central Register. Only obabotulinumtoxinA (obaBTX-A), onabotulinumtoxinA (onaBTX-A), and incobotulinumtoxinA (incoBTX-A) were considered. The term “high dosage” indicated ≥ 600 U. Thirteen studies met the inclusion criteria. Studies had variable method designs, sample sizes and aims, with only two randomised controlled trials. IncoBTX-A and onaBTX-A were injected in three and eight studies, respectively. BTX-A high doses were used predominantly in treating post-stroke spasticity. No studies were retrieved regarding treating spasticity in MS and SCI. Dosage of BTX-A up to 840 U resulted efficacious and safety without no serious adverse events (AEs). Evidence is insufficient to recommend high BTX-A use in clinical practice, but in selected patients, the benefits of high dose BTX-A may be clinically acceptable.

Specificity of using botulinic toxin type A for blepharospasm treatment

Blepharospasm (BS) is one of the diseases characterized exclusively by involuntary face movements (facial hyperkinesis). Typical clinical manifestations include squinting or increased blinking. Among frequent patients’ complains at the disease onset are unpleasant irritations, a foreign body sensation, itching, dry eyes, and frequent blinking. Dynamism is a typical BS feature: 1) it increases during emotional stress, in stressful situations, during fatigue, eye strain (reading), in bright light; 2) disappears while sleeping; 3) decreases after waking up; 4) «corrective gestures», such as touching skin of the eyelids, paraorbital regions and glabellar region, wearing glasses, chewing or absorbing sweets, other arbitrary movements, affect BS. Botulinum therapy (botulinum toxin type A (BtA) injections, in particular using Relatox, the effectiveness of which has been demonstrated in clinical studies) is considered the «gold standard» in BS treatment. BtA is injected mainly into the orbicular muscle of eye, superficially, into the upper, lower eyelids and outer eye corner. The clinical effect occurs quickly, already in the first week after injection and lasts 3 months or more. Cases of botulinum therapy inefficiency in treating BS and other facial hyperkinesis are extremely rare.The article describes BS main clinical aspects, BtA injection schemes as well as adverse events during the therapy. Electromyography is not mandatory to assess BtA effectiveness in BS treatment, but it is necessary in cases of inefficient therapy, adverse events or the therapy complications. It is particularly important to strictly comply with recommended BtA doses, and that the drug is injected by a certified specialist only. Botulinum therapy for BS patients is a highly effective and, in most cases, the only treatment with a good safety profile.

Intramural Injection of Botulinum Toxin A in Surgical Treatment of a Long Gap Esophageal Atresia-Rat Model.

Anastomosis with minimal tension is desirable in long-gap esophageal atresia. Prior studies in piglets showed that intraesophageal injection of botulinum toxin type A (BTX-A) results in significant esophageal elongation. Our aim was to determine the BTX-A dose, number of injections, and time necessary to elicit maximal response. Adult male Wistar rats (n = 48) were randomly assorted into five groups. Four treatment groups received 2 or 4 U/kg of BTX-A, delivered using two or four injections, and a control group received 0.9% NaCl. Esophagus was removed 6 or 24-hours postinjection and tested ex vivo using a stretch tension device. Subsequently, an optimal dose and time following injection was used to study the effects of BTX-A on anastomotic healing in vivo. Rats (n = 12) received an intraesophageal injection of BTX-A or 0.9% NaCl, followed by resection of 0.5 cm of esophagus and end-to-end anastomosis. Rats were observed for 9 days, and esophagus was removed for gross and histological evaluation. The largest effect on elongation was recorded in the BTX-A (2 U/kg) 24 hour, four injection group. In the anastomosis study, stricture formation was observed in all animals in the control group. Absence of esophageal stricture was found in three out of four animals in the treatment group macroscopically and histologically. We found that BTX-A exerts a positive effect on stretch characteristics of esophageal tissue in rats at 2 U/kg via four-injection delivery and 24-hour waiting period. This study suggests that BTX-A might improve anastomotic healing.

Treatment of Post-Facelift Facial Paralysis With Botulinum Toxin Type A

BACKGROUND: Nerve injuries post-facelifts are rare but cause serious functional and psychological impairment of self-esteem and quality of life.1,2 Despite being temporary in most cases, facial asymmetry typically lasts for 3 months. We present a treatment protocol for post-facelift facial nerve injuries using botulinum toxin type A (BTXA). MATERIALS AND METHODS: The study was conducted from January 2002 to June 2018. Nine patients (all female; mean age, 58 ± 8.4 years) with asymmetries due to post-rhytidectomy facial palsies were treated in the nonparalyzed side with abobotulinum toxin type A, with 6-month to 5-year follow-up. The 500-U vial was diluted in 4 ml of 0.9% saline. We considered 0.02 ml of the solution (2.5 abobotulinum toxin units) as 1 volume unit. Patients were examined after 15 days for outcomes evaluation. The dose applied to each muscle group1 varied from 1 to 2 volume unit per point. Patients were retreated after 5–6 months in case of asymmetry recurrence. RESULTS: Four patients sought early care (mean, 14.2 ± 6.4 days postoperative, ranging from 5 to 21 days). The others arrived later (mean, 225 ± 80.7 days postoperative, ranging from 150 to 360 days). Two patients had lesions affecting the upper third of the face, and symmetry was achieved after unilateral treatment of the frontalis muscle. Three patients had injury in the middle third; their treatment depended of analysis of the deviation vectors when smiling and frowning, as to decide which muscle groups should be treated (vertical: upper lip lifter muscles; upper oblique: lifters of the angle of the mouth muscles; and horizontal: risorius muscle). Four patients were affected in the lower third (inferior deviation vectors) and were treated with 2 points to paralyze the lower lip depressor muscles. Correction of asymmetry was achieved in all cases. Recovery from the nerve injury and BTXA application occurred symmetrically in both sides of the face in the following months. All patients with early onset of BTXA therapy (<30 days) had complete recovery of facial symmetry with a single application, evidence of neuropraxis. Patients with lesions of the upper third, those with late onset of BTXA treatment (>30 days), and those with >1 affected nervous branch presented definitive lesion, with partial recovery or improvement, and needed BTXA treatment every 6 months. CONCLUSION: Most facial nerve injuries post-facelifts presented favorable evolution for spontaneous resolution, except in the upper third of the face and in case of late lesions. Symmetry was achieved in all cases with low doses of BTXA in the suggested protocol points, avoiding an unhappy asymmetric patient in the following months. REFERENCES: 1. Salles AG, Toledo PN, Ferreira MC. Botulinum toxin injection in long-standing facial paralysis patients: improvement of facial symmetry observed up to 6 months. Aesthetic Plast Surg. 2009;33:582–590. 2. do Nascimento Remigio AF, Salles AG, de Faria JCM, et al. Comparison of the efficacy of onabotulinumtoxinA and abobotulinumtoxinA at the 1: 3 conversion ratio for the treatment of asymmetry after long-term facial paralysis. Plast Reconstr Surg. 2015;135:239–249.