Botulinum Toxin Type A for Pediatric Torticollis: A Review of Clinical Research

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.

Botulinum toxin type A (BoNTA) has been suggested as an effective anti-spastic drug. In this article, we summarized the data of randomized, placebo-controlled, double- blind trials and conducted a meta-analysis to assess if BoNTA is an adequate treatment for spasticity following stroke. To evaluate the relevant literature and assess the effectiveness and safety of BoNTA in (1) reducing spasticity based on mean change in the Modified Ashworth Scale (MAS) for upper and lower limb spasticity from baseline; (2) reducing spasticity based on the percent of patients having > or = 1point(s) change in the MAS; (3) improving the patient's or caregivers' Global Assessment Scale (GAS); and (4) total adverse events. We selected all randomized, placebo controlled, double-blind clinical trials or previous meta-analyses evaluating the efficacy and safety of BoNTA (Botox or Dysport) for the treatment of spasticity in both upper and lower limbs after stroke. Validity assessment of studies was performed, and Revman 4.2.7 from Cochrane Collaboration and SPSS (statistical package for the social sciences), v 9.0, were applied for analysis. Overall analysis showed clinical improvement between baseline and 4-6 weeks after application of BoNTA of the patient's spasticity score using the MAS (weighted mean difference [WMD] = 0.87, 95% CI = 0.52-1.22). The odds ratio of the MAS spasticity score showing one or more points improvement at 4-6 weeks after giving BoNTA showed clinically significant improvement (OR = 4.5, 95% CI = 2.79-7.25). The odds ratio of having an improved GAS at 4-6 weeks after injecting BoNTA showed clinically significant improvement (Odds ratio = 5.85, 95% CI = 3.12-10.95). The odds ratio of having an adverse event during the entire study did not show any significant difference between placebo and BoNTA (odds ratio = 0.84, 95% CI = 0.55-1.28). BoNTA improves muscle tone in upper and lower limb spasticity following stroke. A global assessment of improvement was noted by the patients or the caregivers following BoNTA injection. BoNTA is considered a safe therapeutic agent.

Hereditary spastic paraplegia presents spasticity as the main clinical manifestation, reducing gait quality and producing incapacity. Management with botulinum toxin type A (BoNT-A) is not well elucidated. The objective of the current study was to evaluate the efficacy and safety of BoNT-A in patients with hereditary spastic paraplegias. This was a double-blind, randomized, placebo-controlled crossover trial. Each participant was randomly assigned to receive 1 injection session of either BoNT-A (100 IU/2 mL of Prosigne in each adductor magnus and each triceps surae) or saline 0.9% (2 mL). The primary outcome measure was change from baseline in maximal gait velocity, and secondary outcome measures included changes in gait at self-selected velocity, spasticity, muscle strength, Spastic Paraplegia Rating Scale, pain, fatigue, and subjective perception of improvement. We also looked at adverse events reported by the patients. We enrolled 55 patients, 36 of whom were men and 41 with the pure phenotype. Mean age was 43 ± 13.4 years (range, 19-72 years), mean age of onset waws 27 ± 13.1 years (range, <1 to 55 yars), and mean disease duration was 17 ± 12.7 years (range, 1-62 years). Compared with baseline, we did not find significant differences between groups in primary and secondary outcomes, except for reduction in adductor tone (P=0.01). The adverse events were transient and tolerable, and their incidence did not significantly differ between treatments (P=0.17). BoNT-A was safe in patients with hereditary spastic paraplegias and reduced the adductor tone, but it was not able to produce functional improvement considering the doses, injection protocol, measures, and instruments used. © 2021 International Parkinson and Movement Disorder Society.

Tremor is one of the most common movement disorders. It does not usually respond to first-line drug treatments (e.g. propranolol, primidone, anticholinergics, gabapentin and clonazepam) due to side effects and frequent dose limitations. Botulinum toxin type A (BoNT-A) has been widely used to treat tremor, but its efficacy and safety are uncertain. To evaluate the efficacy and safety of BoNT-A in the treatment of hand tremor. We searched the MEDLINE, EMBASE, PsycINFO and Cochrane Library databases for relevant randomised controlled trials of the effects of BoNT-A injections on tremors, up to 20 February 2020. A meta-analysis of comparative effects was performed using R studio software, and publication bias was examined using Egger's test. Six studies examining a total of 245 participants with tremor were included in the meta-analysis. The primary outcome of meta-analysis showed no difference in clinical tremor scale scores between the BoNT-A group versus the placebo group (standardised mean difference (SMD): -0.42, 95% confidence interval (CI): -1.94 to 1.10; I2 = 96%). For clinical tremor scale scores, subgroup analyses suggested that the BoNT-A group may differ in terms of multiple sclerosis (MS) related tremor (SMD: -1.10; 95% CI: -2.17 to -0.04; I2 = 79%) compared to a placebo, but the difference did not exist in the outcome of essential tremor (ET) or hand tremor (MD: -1.31; 95% CI: -3.39; 1.31; I2 = 97%). Grip strength (MD: -1.25, 95% CI: -5.99 to 3.50, I2 = 97%) was slightly lower in the BoNT-A group, but the difference was not significant. The incidence of adverse events (AEs), including hand weakness (RR: 2.96, 95% CI: 1.40 to 6.24, I2 = 37%), was significantly greater in the BoNT-A group than in the placebo group. Two studies were assessed as having an overall low risk of bias. Our study confirms that BoNT-A injections are unlikely to have an impact on patients with hand tremors. However, subgroup analysis suggested that BoNT-A injections could have possible benefits in MS-related tremor. While moderate to severe hand weakness AEs often limits their use in clinical practice, additional well-designed double-blind, placebo-controlled trials are needed to provide more robust conclusions.

Active prevention and treatment of scars are particularly important. Several studies have used botulinum toxin type A(BTXA) to prevent postoperative scarring. The aim of this systematic review and meta-analysis was to systematically evaluate the efficacy and safety of BTXA in preventing and treating postoperative scars. A computer-based search was conducted for the five databases including PubMed, Cochrane Library, EMBASE, CNKI, and Wanfang up to May 22, 2019, to collect the relevant literatures on BTXA treatment of postoperative hypertrophic scars. A meta-analysis was made with the software of Revman 5.3 based on the study endpoint of scar width, Vancouver Scar Scale (VSS), Visual Analogue Scale (VAS) scores, and patient satisfaction as well. A total of 18 randomized controlled trials (RCTs) studies were included with 915 patients in all. The result showed that, compared with the control group, the scar width, VAS scores, and VSS scores of the BTXA group were significantly improved and higher patient satisfaction was achieved. BTXA has a certain curative effect on postoperative scar prevention and treatment without obvious side effects.

Congenital Muscular Torticollis and Positional Plagiocephaly

On the basis of observational studies, child health practitioners in primary care settings should consider the diagnosis of congenital muscular torticollis (CMT)in infants with risk factors from birth history for intrauterine malpositioning or constraint (C). On the basis of observational studies, CMT is often associated with other conditions, including positional plagiocephaly and gross motor delays from weakened truncal muscles and/or lack of head control in early infancy (C). On the basis of observational studies, child health practitioners should counsel parents that infants should be on their stomachs frequently whenever they are awake and under direct adult supervision to develop their prone motor skills (C). On the basis of consensus, early identification of CMT(with or without positional plagiocephaly) and prompt referral to a physical therapist experienced in the treatment of CMT should be considered to avoid more costly or invasive treatments, such as cranial orthoses or surgery (D).

This study aims to evaluate the clinical outcomes of children with spastic type cerebral palsy (CP) treated with botulinum toxin type A (BoNT-A) injection for lower limb contracture and the influence of age, gender, functional level and degree of initial contracture on treatment outcomes. Clinical records at pre-BoNT-A injection and post-BoNT-A injections of 153 sessions of a total of 118 consecutive children (67 boys, 51 girls; mean age 5.9±2.6 years; range, 2.5-16 years) were retrospectively evaluated. Degrees of pre- and post-injection contracture were evaluated. Post-injection supplemental casting for 10 days was recorded in all cases. Less than 20° of hip flexion contracture, more than 30° of hip abduction, a negative prone Ely test, less than 50° of popliteal angle and at least 5° of ankle dorsiflexion values at post-injection were accepted as sufficient clinical improvement. Sufficient post-injection range of motion (ROM) was observed in 80% of cases with hip flexion contracture, in 45% of cases with hip adduction contracture, in 84% of cases with knee flexion contracture and in 77% of cases with ankle equinus contracture. Prone Ely test that was positive in 60% of cases with knee extension contracture was negative at post-injection. Improvement in contractures were prominent in children with lesser degree initial contractures. Botulinum toxin type A injection increases ROM in hip, knee and ankle joint contractures in CP. Although age, gender and functional level may influence the clinical outcomes, pre-treatment level of contracture is the main determinant in improvement in ROM at post-injection.

We evaluated the safety and effectiveness of botulinum toxin A (BoNT/A) in the treatment of spasticity in 20 children with spastic diplegic cerebral palsy (CP). All the patients received injections in the gastrocnemius and soleus, and 15 received injections in the adductors. The total dose varied from 70 to 140 U (99.75±16.26 U), or 7.45 ±2.06 U/kg per patient. The treatment improved the patients' walking and gait pattern significantly. There was also a significant alteration in the heel-ground distance and increased motion of the ankle joint. These structural changes in the feet were sustained until the end of the follow-up, although the same was not observed for the functional parameters. Three patients complained of weakness in the lower limbs. In conclusion, BoNT/A is safe and effective when used in a single session of injections and produces a sustained structural modification of the lower limbs. However, functional changes are temporary and are only observed during the peak effect of the drug.

Botulinum toxin type A (BTX-A) is a potential treatment for chronic rhinitis. This study aimed to assess the effectiveness and safety of BTX-A in treating patients with chronic rhinitis. Systematic searches of MEDLINE, Scopus, and EMBASE databases were performed. Randomized controlled trials (RCTs) that assessed the efficacy of BTX-A in allergic rhinitis and/or nonallergic rhinitis patients, compared with either placebo or active treatment, were included. The outcomes were total nasal symptom (TNSS), disease-specific quality of life (QOL), and adverse events. Nine RCTs (340 patients) met the eligibility criteria. Compared with placebo, the ≤ 12-week effects favored BTX-A injection on TNSS (standardized mean difference [SMD] -2.22, 95% confidence interval [CI] -3.27 to -1.17, p<0.01, four RCTs). Beneficial effects>12 weeks over placebo (MD -9.69, 95% CI -11.29 to -8.09, p<0.01, one RCT) were demonstrated up to 24weeks. However, the benefits were not shown on nasal congestion and individual nasal symptoms. Compared with active comparators (triamcinolone injection, ipratropium bromide, and cetirizine), there was no difference in the<12-week effect between groups on TNSS. There was no difference between BTX-A and cetirizine on QOL (one RCT). The>12-week effects on TNSS and individual nasal symptoms favored BTX-A over triamcinolone injection (one RCT). The risk ratio of adverse events favored BTX-A over cetirizine (one RCT). BTX-A improved TNSS and QOL in patients with chronic rhinitis. These effects were demonstrated up to 24weeks post treatment. BTX-A was safe, well tolerated, and may be considered in patients who are refractory to current standard-of-care therapies.

Combination treatments using hyaluronic acid (HA) fillers and botulinum toxin Type A (BoNT-A) are common in aesthetic medicine; however, this has been evaluated in only a few clinical studies. To evaluate subject satisfaction, efficacy, and safety of BoNT-A (Speywood Unit; s.U) and a range of HA fillers for full-facial aesthetic rejuvenation. A 6-month, multicenter, open-label clinical study, using BoNT-A (s.U) and 5 HA fillers to treat up to 13 facial zones. Subject satisfaction questionnaires were administered 3 weeks and 6 months after the last injection. Global aesthetic improvement and improvement on each treated zone as well as safety were evaluated. A high level of satisfaction was achieved throughout the study, with 96.5% of subjects at least satisfied with the full-facial aesthetic outcome at 3 weeks, and 92.9% at 6 months. More than 91% considered the treatment outcome to meet or surpass their expectations, and more than 94% would recommend the treatment to others. At Week 3, subject and investigator assessment showed aesthetic improvement for all subjects. The treatment was well tolerated. The combination of BoNT-A (s.U) and HA fillers results in high patient satisfaction and in an overall improvement of aesthetic outcomes and quality of life.

Background:Palmar hyperhidrosis, a condition characterized by excessive sweating in the palms, considerably impacts the quality of life (QoL). Although various treatment modalities are available, the efficacy and safety of Botulinum toxin type A (BTX-A) needed further investigation. Methods:We conducted a literature review, with open-label, controlled trial, double-blind placebo-controlled and observational designs being eligible for inclusion, according to the PRISMA guidelines. Results:All the six selected studies consistently reported the efficacy of BTX-A in reducing symptoms of hyperhidrosis, without significant side effects. Botulinum toxin type A treatment was found to improve the QoL significantly, to reduce sweat rate and production and to have no detrimental effect on grip strength. The duration of the antisudorific effect also indicated the potential for long-term management of palmar hyperhidrosis with BTX-A. Conclusions:Our findings corroborated the effectiveness and safety of BTX-A in managing palmar hyperhidrosis across diverse patient outcomes and experiences. Botulinum toxin type A emerged as a promising treatment modality for this condition, capable of improving the QoL, reducing symptoms and offering long-term relief without significant side effects.

Expanding use of botulinum toxin

Background: Botulinum toxin type A (BTA) has a wide range of clinical applications, and its use in improving aesthetics is one of them. The aim of this study was to better assess the efficacy and safety of BTA in patients with facial scars. Summary: We extracted the data of the visual analog scale (VAS) score, Vancouver scar scale (VSS) score, scar width, observer scar assessment scale (OSAS), patient scar assessment scale (PSAS), and/or drug-related adverse events. Five studies provided the data of VAS score, and the results showed that the VAS score in the BTA group was significantly higher than that in the control group. Three randomized controlled trials (RCTs) reported the VSS score. A statistically significant difference exists between the BTA group and the control group. Three RCTs reported the scar width after BTA treatment. A more favorable change was found in the BTA group with scar width even without statistical significance. Data about the OSAS and PSAS scores were available in two trials. There was no significant difference in OSAS and PSAS scores between the BTA group and the control group. Only three studies recorded three slight adverse events. There were no reports of severe complications. In conclusions, this study demonstrated that BTA has the potential to improve facial scars with an acceptable safety profile.

Botulinum toxin type A (BTA) is applied in muscle hyperactivity disorders and injected into affected muscles, producing deep and persistent muscle relaxation. Several multidisciplinary groups investigated the treatment of temporomandibular disorders for several years, and there is currently some data on the beneficial effects of BTA in specific cases of chronic masticatory myalgia. Percutaneous needle electrolysis (PNE), which applies a low-intensity galvanic current to promote tissue regeneration, has been shown to be effective in reducing pain and improving masticatory function. The purpose of this study was to investigate the efficacy and safety of BTA and to assess whether its application in patients with localized masticatory myalgia can significantly reduce pain and improve function compared to a group treated with PNE. Fifty-two patients with long-term refractory masticatory myalgia were randomly assigned to two groups. The BTA group (n = 26) received a bilateral botulinum toxin injection and the PNE group (n = 26) received percutaneous electrolysis. The dose of BTA injected was 100 units distributed among the main primary masticatory muscles, and PNE was administered at 0.5 mA/3 s/3 consecutive times in a single session. Patient assessments were performed prior to treatment and one, two, and three months after treatment. The results revealed good therapeutic response in both groups. In the long term, both BTA and PNE showed high efficacy and safety in reducing pain and improving muscle function for the treatment of chronic masticatory myalgia. This improvement was sustained over a three-month period in both groups. Therefore, the use of BTA and PNE could be considered a valid and safe therapeutic alternative among the available options to treat refractory and localized masticatory myalgia when a better therapeutic response is expected as it demonstrated high efficacy.