Efficacy and Safety of PrabotulinumtoxinA in Subjects With Benign Masseteric Hypertrophy: A Double-Blind, Randomized, Placebo-Controlled, Multicenter, Phase 3 Trial and Open-Label Extension Study.

BACKGROUND: Despite the widespread use of botulinum toxin (BTX) injection for the treatment of masseter muscle hypertrophy (MMH), there is no standard treatment option. OBJECTIVE: We report the efficacy and safety for BTX in MMH over a period of 48 weeks. METHODS: In double-blinded, placebo-controlled phase 3 trials, 180 patients (randomized 1:1) received treatment with placebo (normal saline) or prabotulinumtoxinA (48 units). Masseter muscle thickness (at maximal clenching and resting positions), 3D imaging analysis, and masseter muscle hypertrophy scale grades were analyzed at each time point. After the 24-week CORE study, all patients who met the same criteria of the CORE study at week 24 ( n = 114) received only prabotulinumtoxinA, regardless of previous treatment, for an additional 24 weeks (48 weeks in total) for the open-label extension study. RESULTS: The largest differences in mean and percent changes from baseline in masseter muscle thickness were observed at 12 weeks, and there were significant differences between the 2 groups at all time points (all p < .001). The effect was independent of the number of injections. No serious adverse event was observed. CONCLUSION: PrabotulinumtoxinA could effectively ameliorate MMH without major complications.

Neuromodulator Finesse for Masseter Hypertrophy and Bruxism.

SUMMARY: A particularly prominent mandibular angle or a hypertrophied masseter muscle can result in an excessively wide facial appearance, which some individuals may find less aesthetically pleasing. Although normally a benign condition and strictly an aesthetic concern, a hypertrophied masseter can also cause pain, bruxism, and headaches. Neuromodulator for masseter reduction and treatment of bruxism has become first-line treatment. In this article, the authors present the senior author's (R.J.R.) anatomic approach to neuromodulator injection of the masseter, with a corresponding video of the injection technique.

Assessment of Electromyographic Changes in a Patient with Masseter Hypertrophy and Muscle Pain after Botulinum Injections: A Case Report and 5 Months Follow-up.

AIM: To determine if botulinum injections in masseters could be an option to avoid surgery and prolonged treatment with occlusal splints and/or drugs to care for both painful bruxism and cosmetic improvement in a patient with a square jaw, bruxism, and orofacial pain. BACKGROUND: Masseter muscle hypertrophy (MMH) is a benign, unilateral, or bilateral, painless enlargement in the lower face. It presents as a symmetrical or asymmetrical increase in the masseter muscle. Masseter muscle hypertrophy (MMH) sometimes can be related to bruxism symptoms like muscle and/or temporomandibular joint (TMJ) pain. CASE DESCRIPTION: A 38-year-old woman complained of bilateral pain at palpation in the masseter body. She also complained about esthetics because of the prominent masseter muscle in the face and square face shape. A diagnosis of bruxism-related myalgia was performed, and treatment with botulinum injections into the masseter muscles was opted for. An oral electromyography was performed to detect the electrical muscular activity of masseter muscles over time. CONCLUSION: After a drastic reduction in the mean electrical activity immediately after the botulinum injections, a progressive increase in strength over time was noted, testifying about the decrease in the effect of botulinum over time. The pain disappeared for 5 months after the injections of botulinum. The reduction of the masseter muscle mass led to a softening of the face shape. CLINICAL SIGNIFICANCE: This case report shows that treatment with botulinum can lead, in the short term, to a reduction in orofacial pain due to a decrease in muscle electrical activity.

A Cadaveric Study of Dye Spreading: Determining the Ideal Injection Pattern for Masseter Hypertrophy.

BACKGROUND: Masseter hypertrophy is the main cause of an asymmetrical and squared lower facial contour in the Asian community. Botulinum toxin injection technique is crucial to treat this condition. OBJECTIVE: To improve injection techniques for masseter hypertrophy by elucidating the distribution of the injections within the masseter. METHODS: Thirty masseter muscles were divided into 6 groups of 5 muscles each. Each group received one 0.2- or 0.3-mL injection at Point A, B, or C according to a three-point technique. Muscle dimensions and dye of the primary and secondary dye spreading were measured. RESULTS: The average muscle length, width, and thickness were 69.87, 33.50, and 11.23 mm, respectively. The average primary longitudinal and horizontal spreading was 36.56 and 15.60 mm, respectively. No statistically significant difference was found between 0.2- and 0.3-mL injections at each point. CONCLUSION: The three-point technique best fits in the safe zone and should be the standard injection technique for masseter hypertrophy. Injection at Points B and C may create secondary spreading that affect the risorius muscle and the parotid gland which are the cause of asymmetrical smiling and xerostomia, respectively. The dosage should be adjusted according to the muscle volume and not only the thickness.

Management of unilateral idiopathic masseter muscle hypertrophy with botulinum toxin type A.

Masseter hypertrophy (MH) is an uncommon disorder which can cause both aesthetic and functional problems. The most common aetiological factors associated with MH are habit of chewing gum, clenching and/or bruxism. The treatment of MH includes conservative management as well as surgical resection of the enlarged muscle and/or bone. Injection of botulinum toxin type A is a relatively new and minimally invasive method for management of masseter muscle hypertrophy, which offers many advantages over conventional surgical management. This paper reports a case of unilateral MH of unknown origin which was treated with injection of botulinum toxin type A, resulting in satisfactory reduction in the volume of muscle and improvement of facial aesthetics.

Efficacy and Safety of a Novel Botulinum Toxin A for Masseter Reduction: A Randomized, Double-Blind, Placebo-Controlled, Optimal Dose-Finding Study.

BACKGROUND: A wide lower face and a square jaw are considered esthetic problems, particularly in Asia. OBJECTIVE: To investigate the optimal dose of a novel botulinum toxin (prabotulinum toxin A) for treating masseteric hypertrophy. METHODS: Ninety subjects with masseteric hypertrophy were randomly divided into 5 groups and treated with placebo (A, normal saline) or prabotulinum toxin A (B: 24, C: 48, D: 72, and E: 96 units). Photography, ultrasonography, and 3-dimensional imaging were performed before and after injection at baseline and at 4, 8, 12, and 16 weeks after treatment. The participants also rated their satisfaction. RESULTS: Masseter thickness significantly reduced in all groups at 12 weeks, compared with that in the placebo group. A dose-dependent reduction in masseter thickness was observed at the resting and maximal clenching positions. Sonography and 3-dimensional imaging revealed a gradual reduction in masseter thickness and volume, respectively, during the first 12 weeks. Despite being slightly effective, a dose of 24 units might be insufficient for resolving square face problems. Patients in Group E reported discomfort during jaw movement. CONCLUSION: Prabotulinum toxin A could effectively improve lower face contour without major complications, with an optimal dose of 48 to 72 units, followed by reinjection after 12 weeks.

Alternative Clinical Indications of Botulinum Toxin.

Botulinum toxin type A (BoNTA) is a powerful neurotoxin that inhibits acetylcholine release from presynaptic vesicles. The potency and safety profile of BoNTA grant the toxin vast therapeutic potential. It has been used off-label for a variety of dermatologic conditions. This review aims to analyze published literature regarding the benefits and risks of the off-label use of BoNTA beyond facial lines, including eccrine hidrocystomas, enlarged pores, keloids and hypertrophic scars, hidradenitis suppurativa, hyperhidrosis, masseter muscle hypertrophy, and salivary gland hypertrophy, among others. A MEDLINE search from January 2000 to December 2019 was conducted on the off-label uses of botulinum toxin in dermatology.

Efficacy of Botulinum Toxin in Treating Asian Indian Patients with Masseter Hypertrophy: A 4-Year Follow-Up Study.

BACKGROUND: Asian Indians usually have wide lower faces because of masseter hypertrophy. The authors evaluated the efficacy of botulinum toxin type A in long-term management of bilateral masseter hypertrophy in Asian Indian patients. METHODS: Fifty patients were enrolled in the study and injected with 30 U of botulinum toxin type A to each side of the face, at baseline. Based on masseter muscle thickness and response to the injections, 25 patients underwent a second injection session at week 12, and the other 25 patients underwent additional third sessions, at week 24 after the first injection, respectively. Standardized photography and ultrasonography were performed to assess facial contour and masseter muscle thickness at baseline and at 1-, 2-, 3-, and 4-year follow-ups. A p value < 0.05 was considered statistically significant. RESULTS: The authors observed 12 percent (p < 0.0001) average masseter muscle size reduction at week 12. The maximum reduction (26.6 percent; p < 0.0001) was observed at week 24 for the patients who received two injections and maintained an average 24.43 percent (p < 0.0001) reduction until follow-up at year 4. Patients who received three injections exhibited very high reduction (42.52 percent; p < 0.0001) of masseter volume at week 36 and maintained an average 40.64 percent (p < 0.0001) reduced volume until year 4. CONCLUSIONS: Botulinum toxin type A treatment is effective for long-term management of bilateral masseter hypertrophy. Doses repeated at 12-week intervals accentuate masseter volume reduction and also help maintain reduced masseter volume for 4-year follow-up, with satisfactory facial contour.

Ultrasonographic Evaluation of The Effects of Orthodontic or Functional Orthopaedic Treatment on Masseter Muscles: A Systematic Review and Meta-Analysis.

Objectives: This review investigated the effects of orthodontic or functional orthopedic therapy on masseter muscle thickness through the use of ultrasonography (US) in growing subjects when compared with untreated subjects. Materials and Methods: This review systematically assessed studies that investigated growing subjects undergoing orthopedic therapy for the correction of malocclusion of vertical, sagittal and transversal plane. Electronic databases (CENTRAL, MEDLINE-PubMed, Scopus and Web of Science) were searched up to February 2019, including available RCTs and CCTs, without language restrictions. The primary outcome was the effect of orthopedic or functional treatment on masseter muscle thickness. The risk of bias of included studies was assessed through the Newcastle-Ottawa quality assessment scale with the aim of defining their methodological quality. A random-effects meta-analysis analyzing mean differences with 95% confidence intervals was used for quantitative analysis. Results: The search retrieved 749 titles, but the studies selection resulted in a final sample of 5 CCTs. The studies retrieved data from 233 children (age range: 5-22 years) and were conducted at university dental clinics. Children were treated for Class II malocclusion, increased vertical dimension or lateral cross-bite variably with rapid or slow maxillary expansion, twin block, bite block, mandibular activators, quad helix, alone or in combination. Risk of bias was assessed as medium for three studies, low for one and high for another. The meta-analysis determined that at the end of orthopedic or functional treatment masseter muscle thickness, measured through the use of US, is significantly reduced (MD -0.79 mm; 95% CI -1.28 to -0.31). The reduction in muscle thickness, therefore, could be considered an indicator for the evaluation of the success of therapy with orthodontic appliances. Conclusions: Although the meta-analysis revealed that US could be considered a less invasive and effective method to evaluate the masseter muscle thickness, single-blinded RCTs, are required to confirm US reliability in this field of application. This review was registered on PROSPERO with the following registration number: CRD42018068402.

Botulinum Toxin Injections for Masseter Reduction in East Asians.

BACKGROUND: Cultural ideals for a slimmer face have led to an upsurge in interest in facial contouring among East Asians. Although surgical resection has traditionally been the main treatment option, botulinum toxin injection is becoming a popular, noninvasive alternative. OBJECTIVE: To describe the use of botulinum toxin injection for masseter reduction in East Asians. METHODS: An electronic search of the PubMed database was performed for studies published from 2000 to 2017 that meet the word combination of botulinum toxin, masseter, hypertrophy, and/or lower face contouring. Only the studies conducted in East Asian countries were analyzed in this review, exception of one study from Thailand. RESULTS: A total of 12 publications were identified. Each study was reviewed to extract relevant information on patient selection, injection techniques, efficacy, dosage, frequency, and main side effects of treating masseters with botulinum toxin. CONCLUSION: Botulinum toxin injection for masseter reduction in East Asians is efficacious and generally considered safe with no significant side effects. Future areas for investigation include defining the criteria for benign masseteric hypertrophy, minimum effective dosage of botulinum toxin, and the potential long-term effects of the injection.

Masseter Muscle Volume Changes Evaluated by 3-Dimensional Computed Tomography After Repeated Botulinum Toxin A Injections in Patients With Square Facial Morphology.

INTRODUCTION: Botulinum neurotoxin A (BoNT-A) is a minimally invasive and technically straightforward treatment of masseter muscle (MM) volume reduction and facial contouring, but the literature on its long-term effect on MM volume remains unclear. OBJECTIVE: This study aimed to assess quantitatively for progressive volume changes of lower facial contour after 3 BoNT-A injections in patients with bilateral MM hypertrophy causing square facial morphology using 3-dimensional computed tomographic scans. MATERIALS AND METHODS: Ten female patients with square facial morphology due to bilateral MM hypertrophy were recruited to, and 6 completed, this clinical study. Each received 24 U of BoNT-A into the inferior portion of each MM on both sides, repeated 6 monthly to complete 3 treatments. Masseter muscle volume changes were assessed using 3-dimensional computed tomography at pretreatment (before injections) and posttreatment (1 year after the third injection). RESULTS: Mean MM volume significantly reduced from 26.39 ± 4.18 cm before treatment to 23.26 ± 4.31 cm 1 year after treatment (P = 0.002). CONCLUSION: Three consecutive 6-monthly BoNT-A injections into the MMs reduced their volume by 12% when assessed 1 year after completion of treatment.

Ultrasonographic diagnosis of benign masseter muscle hypertrophy: A case report.

Masseter hypertrophy is a characteristic condition resulting from an increase in the size of the muscle mass. At times, it produces significant facial asymmetry and is an important finding in the differential diagnosis of similar located entities. A proper diagnosis of this condition would avoid more aggressive and unwarranted therapy by an inexperienced clinician who may mistake it for a more serious pathologic condition. This article reports two cases of bilateral masseter hypertrophy having characteristic diagnostic features, along with specialized imaging modalities and review of literature.

Does Botulinum Toxin Injection into Masseter Muscles Affect Subcutaneous Thickness?

BACKGROUND: Botulinum toxin (BoNT) is widely used to treat masseter muscle hypertrophy. Changes in the muscle thickness have been found in many studies, but there has been no report on changes in the thickness from the skin surface to the masseter muscle. OBJECTIVES: We aimed to use ultrasonography to measure not only changes in the muscle thickness but also changes in subcutaneous thickness. METHODS: This study enrolled 20 volunteer patients: 10 were assigned to an experimental group (injected with each side 25 U of botulinum toxin into both masseter muscles) and 10 to a control group (injected with normal saline). The thicknesses were measured before the injection and at 4, 8, and 12 weeks after the injection both at rest and during maximum muscle contraction. RESULTS: The subcutaneous thickness did not differ significantly over time either at rest (P = 0.063) or during maximal contraction (P = 0.392), or between the experimental and control groups at rest (P = 0.392) or during maximum contraction (P = 0.259). The muscle thickness in the experimental group differed significantly over time. CONCLUSIONS: Botulinum toxin injection only changes the muscle thickness and does not affect the subcutaneous thickness from the skin surface to the masseter muscle.

Surgical Resolution of Bilateral Hypertrophy of Masseter Muscle Through Intraoral Approach.

Masseter muscle hypertrophy is an untypical anomaly with no definite cause and its diagnosis is easily completed through physical examination and imaging examinations. In some cases, patient may report signs and symptoms of well-localizated pain. However, it is generally asymptomatic and patient's chief complaint is about esthetic because of facial asymmetry. In this case, surgery is carefully indicated. The aim of this article is to report a case of a male patient with no painful and functional complaints but an important unease over his facial asymmetry. Patient underwent surgery involving bilateral resection of mandibular angles and unilateral resection of masseter muscle through intraoral approach. Surgical approaches and techniques rely heavily on surgeon. There are few reports in the literature about this anomaly, but those available present several techniques. The surgeon's dexterity and knowledge become extremely important, whereas this procedure is essentiallyesthetic.

Simultaneous Bilateral Hypertrophies of the Parotid Gland and Masseter Muscle: Case Report.

Increased salivary demand can lead to enlarged parotid salivary glands, and increased activity of the masseter muscles can cause masseter hypertrophy. This report describes a most unusual case of simultaneous bilateral hypertrophies of the parotid gland and masseter muscle originating from the very extensive habit of chewing gum. An extensive literature review uncovered many cases of the independent existence of masseteric or parotid hypertrophy, but no example of the simultaneous occurrence of these 2 conditions.

Bilateral hypertrophy of masseteric and temporalis muscles, our fifteen patients and review of literature.

OBJECTIVE: The association of bilateral hypertrophy of temporalis and masseteric muscles is a rare clinical entity. The origin of the condition is unclear, causing cosmetic problems, pain, and functional impairment. PATIENTS AND METHODS: In this paper we analyzed 15 patients treated at the Department of Maxillo-Facial Surgery of the University of Naples Federico II, from 2000 to 2013, for temporalis and/or masseteric muscle hypertrophy, and in particular, a rare case of a patient with a marked bilateral swelling of the temporalis and masseteric region, in conjunction with a review of the literature. RESULTS: Fourteen patients have not any kind of postoperatively problems. The last patient had been aware of the swelling for many years and complained of recurrent headaches. We adopted a new protocol fort this patients and the patient was very pleased with the treatment results, and reported a reduction in headaches and a continuation of his well-being, in addition to greater self-confidence. The last follow-up was performed three years after the first treatment, and the patient showed a complete resolution of his symptoms, and just a small increase of the swelling. CONCLUSIONS: The treatment of temporalis and masseteric hypertrophy with Botulin toxin could be an effective option compared to conservative treatment or surgical intervention, although the review of the literature shows that this is only a temporary treatment. In fact, surgery still remains the best option. The treatment must be repeated every 4/6 months for 2-3 consecutive years before having stable benefits. To overcome this problem, an association with a bite treatment allowed us to achieve more lasting and more stable results over time without a recurrence of symptoms between the treatments. Furthermore, this association has enabled us to obtain a more rapid reduction of the hypertrophy.

[Quantitative analysis based on three-dimensional stereophotogrammetry in the observation of curative effect of botulinum toxin A on masseter hypertrophy].

Objective: To observe the curative effect of botulinum toxin A on masseter hypertrophy using three-dimensional stereophotogrammetry. Methods: 46 cases with masseter hypertrophy (92 masseters) who received botulinum toxin A injection were enrolled from May 2013 to August 2014.Data were collected before and 3,6 and 9 months after injection. Results: The efficacy of botulinum toxin A in reducing the volume of the lower face has been proven by MAS 3D.3 and 6 months after injection, the volume reduction were measured as 7.23 ％,2.15％ respectively (P ＜ 0.05).The coefficients between middle and lower thirds of the face showed an increase compatible with thinning of the lower face with statistical significance at 3 months follow up. The increase percentage was measured by MAS 3D as 40.21％ between pre-and post-injection (P ＜ 0.05),and the increase percentage was 21.03％ at 6 months follow up (P ＜ 0.05).While 9 months after injection,the value was insignificant comparing to pretreatment at 9 months. Conclusions: Three-dimensional stereophotogrammetry provides a safe effective and direct way to observe masseter hypertrophy.

[Noninvasive monitoring of changes in the structure and function of masseter muscles after the injection of botulinum toxin type A].

Objective: To evaluate the effect and maintaining period of botulinum toxin A on the masseter muscles through noninvasive monitoring of changes in the structure and function of masseter muscle. Methods: We randomly selected 20 female patients with benign masseter hypertrophy,22-43 years old, who were treated with injection of botulinum toxin A. High-frequency ultrasound was adopted to measure thickness and hardness of muscles.Surface electromyography (sEMG) was used to observe the changes of muscle force. All patients were followed up before and 1,4,12 and 24 weeks after the injection of botulinum toxin type A. Subjective evaluation of the efficacy was performed by questionnaire survey. Results: The thickness and hardness of muscle decreased 1 week after injection which attained the lowest level at 12 weeks. The thickness and hardness reduced by 18％-39％ and 20％-32％ respectively at relaxed state of masseter muscles, the muscle force reduced by 78％ during muscle contraction. The muscle recovered to previous state 24 weeks after injection. The subjective evaluation by doctor and patients was consistent with the results by the high frequency ultrasound and EMG detection results. Conclusions: High frequency ultrasound and surface electromyography are effective and noninvasive means for objective evaluation of masseter muscles after the injection of botulinum toxin type A.