Xie, Yun M.D.; Zhou, Jia M.D.; Li, Haizhou M.D.; Cheng, Cheng M.D.; Herrler, Tanja M.D.; Li, Qingfeng M.D., Ph.D.
Masseter hypertrophy may cause a prominent mandibular angle, resulting in an unattractive wide contour of the lower face. Etiologic factors include mental stress and bruxism, but also work hypertrophy from chewing.1 In 1994, Moore and Wood introduced botulinum toxin type A injection of the hypertrophic masseter to treat functional problems.2 Later, Rijsdijk et al. began to use botulinum toxin type A for aesthetic volume reduction of the hypertrophic masseter.3 In contrast to conventional surgery, botulinum toxin type A injection is a minimally invasive technique, and is easy and safe to handle.4 Especially in Asian populations that tend to have a wider contour of the lower face,5–7 it has become a first-choice treatment for masseter hypertrophy.
A review of the literature showed that a criterion standard for the use of botulinum toxin type A in the treatment of masseter hypertrophy is lacking. In 2005, Choe et al. suggested that more than 20 units of botulinum toxin type A should be injected if masseter thickness exceeded 10 mm (Botox; Allergan, Inc., Irvine, Calif.).8 In the same year, Kim et al. proposed the application of 100 to 140 units for a masseter thickness of 10 to 16 mm (Dysport; Ipsen Ltd, Slough, United Kingdom).5 In a study investigating the influence of botulinum toxin type A injections on the parotid gland, Kwon et al. recommended the injection of 25 units per muscle at two injection sites (BTX-A; Lanzhou Institute of Biological Products, Lanzhou, People’s Republic of China).9 Recently, Gaofeng et al. proposed 30 to 50 units per side (BTX-A),10 whereas Jaspers et al. used 36 units of botulinum toxin type A (Botox) injected at three sites per muscle.11
For a standardized treatment approach, an appropriate assessment method of the pretherapeutic status is pivotal. However, the anatomy of the masseter has not been precisely defined yet and a classification method is lacking. Thus, the extent of masseter hypertrophy has not been considered in clinical trials, resulting in varying dosage and application suggestions. As to the injection technique, partitioned injection at three different sites was used most frequently, but the location of the ideal injection sites remains controversial.9,10 In the present study, we first classified the masseter muscle based on the findings from (1) a large-sample prospective study involving clinical and ultrasound examination and (2) anatomical dissection studies. The classification served as the basis for a personalized botulinum toxin type A injection protocol that was evaluated in a prospective clinical study regarding its safety and efficacy in the treatment of masseter hypertrophy.
PATIENTS AND METHODS
Classification of the Masseter Muscle
A total of 252 cases (504 masseters) were investigated in our clinic between March of 2011 and December of 2011 using clinical and ultrasound examination. The study cohort included 24 men (age range, 19 to 30 years; mean, 23.5 years) and 228 women (age range, 18 to 42 years; mean, 22.7 years). Seventy-four cases had a history of botulinum toxin type A treatment, but not within at least a 1-year interval to exclude any impact of botulinum toxin type A on the masseter. The rest of the patients had never undergone botulinum toxin type A injection.
Clinical examination was performed in all patients, including inspection and palpation of the masseter on resting and clenching. The different bulging types of the contracted masseter were identified based on palpation, because morphologic assessment may be disguised by subcutaneous adipose tissue. B-mode ultrasound (Mindray M5; Mindray Medical International Ltd., Shenzhen, People’s Republic of China) was used to measure masseter thickness. The patient was seated face to face on the right hand side of the investigator. The masseter was scanned on clenching from the bottom upward with the detector placed parallel to the inferior border of the mandible. The thickest part of the masseter was found in the area between the inferior border of the mandible and the virtual line drawn from the angulus oris to the ear lobe. Masseter thickness was determined in an ultrasound cross-sectional view at this point on contraction and resting of the muscle.
Anatomical Study of the Masseter Muscle
Dissection studies of the masseter area in three fresh corpses were performed to elucidate the anatomical correlates of the different bulging types. The layers of the masseter and the branching and course of the masseteric nerve were explored.
Evaluation of Tailored Botulinum Toxin Type A Injection Protocol for the Treatment of Masseter Hypertrophy
A total of 220 cases were treated in our institution between January of 2012 and June of 2012. There were 15 men (age range, 19 to 30 years; mean age, 24.1 years) and 205 women (age range, 18 to 38 years; mean age, 21.5 years). All patients sought treatment for narrowing the lower face contour.
Botulinum Toxin Type A Treatment
All patients were treated according to the respective classification of masseter bulging type and thickness using botulinum toxin type A from Hengli (Lanzhou Institute) that exhibits equal efficiency compared with Botox. Each patient was followed up by telephone call within 2 to 48 weeks. Clinical follow-up at 1, 2, 3, and 4 months after botulinum toxin type A treatment was achieved in 40 patients. Standard photography documentation was performed at each visit. Patients were instructed to immediately present for an unscheduled follow-up if adverse effects occurred in the meantime.
The therapeutic outcome was evaluated using ultrasound examination and morphometric analysis. Sonography was performed by the same investigator in all patients in a blinded manner. Morphometric analysis based on standard patient photographic documentation was conducted by a plastic surgeon not involved in botulinum toxin type A injection. The ratio of the widest part of the lower face to the intercanthal distance was calculated using Photoshop 7.0 (Adobe Systems, Inc., San Jose, Calif.) to compare the therapeutic effect. All complications were recorded. Patients were called for a follow-up interview to assess their impression regarding the therapeutic effect (i.e., remarkable effect, effect, or no obvious effect) and patient satisfaction.
The data were analyzed using the paired t test to compare masseter thickness and the morphometric ratio of the widest part of the lower face to the intercanthal distance before and after treatment using SPSS 12.0 (SPSS, Inc., Chicago, Ill.). Values of p < 0.05 were considered statistically significant.
Bulging Types of the Contracted Masseter Muscle
A total of 504 masseters were examined by palpation and divided into five bulging types on contraction (Table 1). Minimal bulging (type I) was found in 21.4 percent. A single longitudinal bulge was palpated in 33.1 percent and classified as mono bulging type (type II). Type III showed two longitudinal bundles of equal or differing height (28.4 percent). Triple bulging (type IV), characterized by three longitudinal bulges, was found in 6.0 percent. In 11.1 percent, a single excessive bulge was palpable (type V). It is important to note that the bulging types were assessed based on palpation. However, in selected cases, they may be morphologically distinct (Fig. 1).
Masseter Thickness Based on B-Mode Ultrasound Examination
The results from B-mode ultrasound examination were consistent with the clinical classification. The cross-sectional views showed that different types of bulging occur on masseter contraction (Fig. 2). The average thickness measured in 504 masseters was 12.3 ± 2.7 mm. Data showed a normal distribution (Fig. 3). Masseter thickness was classified as mild (lower quartile, <10 mm), moderate (10 to 13.9 mm), and severe (upper quartile, >14 mm) and varied between the different masseter bulging types (Table 2). Statistical analysis showed that the thickness of type V (15.6 ± 1.8 mm) was significantly greater than in the four other types (p < 0.01). The thickness of type IV (13.1 ± 2.2 mm) was also significantly more than in type I (12.0 ± 1.2 mm; p < 0.05) and type II (11.8 ± 2.2 mm; p < 0.05). No other significant differences were found for the remaining groups (Fig. 4).
Anatomical Dissection Studies
Masseter dissection studies were performed to gain a comprehensive understanding about the different bulging types and their anatomical correlative. The masseter was found to be a three-layer skeletal muscle consisting of superficial, middle, and deep layers. The myofibers within these layers were arranged in different directions. The superficial layer arose from the anterior part of the zygomatic arch and passed backward and downward to be inserted into the masseter tuberosity. The thinner middle layer arose from the posterior segment of the zygomatic arch and traveled downward to the front to be inserted into the masseter tuberosity. The deep layer arose from the posterior part of the zygomatic arch, and passed backward and downward to be inserted into the masseter tuberosity. These three layers were separate in the upper two-thirds of the mandibular ramus and intimately fused together in the lower third part. The corresponding nerve trunk of the masseter entered the muscle from its upper edge. Then, it separated into three primary nerve branches and entered the masseter in the superficial, middle, and deep layers, respectively (Fig. 5).
Tailored Botulinum Toxin Type A Injection Protocol
Location of Injection Sites
The setup of a personalized treatment strategy for botulinum toxin type A injection required careful consideration regarding injection dosage and number and location of injection sites. Botulinum toxin type A acts by means of muscle denervation by blocking the presynaptic membrane of the nerve endings at the motor end plate. Therefore, the area of the motor end plate that coincided with the most prominent part of the muscle bulge appeared to be the ideal injection site.
The injection dosage was determined by masseter thickness. Thickness less than 10 mm was considered mild hypertrophy requiring an injection dosage of 20 to 25 units per masseter. Moderate hypertrophy with a thickness between 10 and 13.9 mm demanded a dosage of 25 to 30 units per masseter. Thickness greater than 14 mm showed severe hypertrophy; in this case, a dosage of 30 to 40 units was used.
Number of Injection Sites
In mild masseter hypertrophy or normal masseter with bulging type I (minimal), treatment consisted of a single injection of 20 to 25 units of botulinum toxin type A. In moderate hypertrophy, the drug was distributed evenly across the bulge surface through two injection sites using 12.5 to 15.0 units of botulinum toxin type A per site. For severe hypertrophy, botulinum toxin type A was injected at three different sites and distributed evenly across the bulge surface.
In mono bulging type (type II), the injection was placed at the most prominent point of the bulge. The total dosage per muscle was dependent on the degree of hypertrophy. In severe hypertrophy and a bulge length of greater than 2 cm, botulinum toxin type A was applied at two sites per masseter.
For double bulging masseters (type III), botulinum toxin type A was applied at both bulging points. The total dosage per masseter was determined by the extent of hypertrophy. The dosage per injection site was chosen according to the ratio of the two bulges in height. In severe hypertrophy (i.e., a bulge length >2 cm), the bulge was injected at two sites.
Masseter muscles of triple bulging type (type IV) received botulinum toxin type A injection at the most prominent point on each of the three bulges. The total dosage per masseter was selected depending on the hypertrophic degree of the most prominent bulge. Dosage per injection site was partitioned in analogy to the ratio of the three bulges in height.
In excessive bulging (type V), the masseter was treated at the most prominent point of the bulge using three injections. The total dosage per side was 30 to 40 units, 50 percent of the dosage was applied at the highest point, and 25 percent each was injected adjacent to this site in a triangular configuration. Table 3 shows the personalized botulinum toxin type A treatment at a glance.
Follow-up examinations at 1, 2, 3, and 4 months after treatment were performed in 40 cases using B-mode ultrasonic examination and standard photographic documentation. Average masseter thickness before injection was 12.93 ± 2.91 mm. Compared with preinjection data, a significant reduction in thickness was found during follow-up after 1 month (11.33 ± 2.16 mm; p < 0.05), 2 months (9.56 ± 1.8 mm; p < 0.01), 3 months (8.68 ± 1.71 mm; p < 0.01), and 4 months (9.32 ± 1.73 mm; p < 0.01) after injection (Fig. 6). The minimal value of mean masseter thickness was observed 3 months after botulinum toxin type A injection. The ratio of the widest part of the lower face to the intercanthal distance before injection was 3.3 ± 0.18 compared with 3.03 ± 0.022 at 3 months after injection. The changes were statistically significant (p < 0.01).
Complications occurred in 20 of 220 cases (9.1 percent) as assessed by both interview and clinical follow-up. The complication rate was 60 percent among patients who received higher dosages of botulinum toxin type A. Among the adverse events—dizziness, headache, allergic reaction, insufficient treatment result, abnormal mastication, abnormal activities of the temporomandibular joint, occurrence of an extra bulge (paradoxical bulging), formation of a concave below the zygomatic arch, disappearance of dimples, and unnatural smile—unnatural smile was the most frequent (Table 4). In follow-up interviews, 138 patients (62.7 percent) reported a remarkable effect, 73 patients (33.2 percent) observed an effect, and nine patients (4.1 percent) did not notice an obvious effect. The patient satisfaction rate was 95.91 percent.
Case 1: Symmetric Severe Masseter Hypertrophy, Bulging Type IV
A 31-year-old female patient presented with severe bilateral masseter hypertrophy (thickness, 16.9 mm). Masseter contraction showed a triple bulging type (type IV). A total of 40 units of botulinum toxin type A was injected per muscle at three different sites (5, 30, and 5 units). Three months after injection, masseter thickness decreased to 9.8 mm on the left side and to 8.4 mm on the right (Fig. 7).
Case 2: Asymmetric Moderate/Severe Masseter Hypertrophy, Bulging Type III/II
A 28-year-old male patient sought treatment for asymmetric masseter hypertrophy. Before injection, the left masseter exhibited moderate hypertrophy (thickness, 13.4 mm) associated with double bulging (type III). The right masseter was characterized by severe hypertrophy (thickness, 15.5 mm) with mono bulging (type II). The left side was injected with 30 units of botulinum toxin type A at two sites, whereas 40 units was applied on the right masseter at two sites (20 and 20 units). Three months after injection, masseter thickness was 11.2 mm on the left side and 11.5 mm on the right (Fig. 8).
The commonly used botulinum toxin type A injection techniques for the treatment of masseter hypertrophy aim at evenly distributing the drug within the masseter muscle. As a consequence, higher dosages and injection volumes are required to obtain the desired therapeutic effect. This may not only be associated with a higher rate of adverse reactions such as paradoxical bulging, but might also raise the possibility of drug resistance.12,13 Tailored botulinum toxin type A injection is a novel approach for reducing injection dosage and volume while maintaining the optimal therapeutic effect.
In clinical practice, we found that bulging characteristics of the masseter vary on clenching. In the present study, we identified five different bulging types of the contracted masseter: minimal, mono, double, triple, and excessive (Fig. 9). Dissection studies revealed that the masseter consists of multiple layers that exhibit different directions of muscle contraction. These muscle layers are innervated by separate nerve branches that originate from the nervus massetericus. Strikingly, the localization of the most prominent part of the muscle bulge was consistent with the distribution region of the nervus massetericus in the central V of the lower one-third region.14,15 Because botulinum toxin type A exerts its mode of action by targeting the motor end plate, an injection close to the nerve endings directly at the site of action would allow for reduced injection dosage and volume and a more limited dispersion region.13,16,17 We therefore chose the most prominent point of the bulging muscle as the ideal injection site. The dosage was adapted according to the static thickness of the masseter, because muscle thickness correlates with muscle force and thus the required dosage of botulinum toxin type A.
In the present study, we established and evaluated a tailored botulinum toxin type A injection protocol for varying masseter thicknesses and different hypertrophy bulging types, referring to a prospective clinical trial that suggested 20 units as the minimal effective dosage.8 In a prospective clinical trial, we found that tailored botulinum toxin type A treatment for masseter hypertrophy led to a significant decrease in muscle thickness. Moreover, the contour of the lower face improved after injection, with an overall patient satisfaction rate as high as 95.91 percent. The most distinct therapeutic effects were seen at 3 months after injection. It is important to note that complications observed in the present study were related to high dosages and a wide dispersion region. Complications such as zygomatic and buccal depression, unnatural smile, disappearance of dimples, and paradoxical bulging were consistent with previous reports.12,14,18
The present study is limited by a loss of patients to follow-up. A comparative study regarding the different masseter bulging types and degrees of thickness with close follow-up examinations would allow for a deeper understanding and establishment of a more differentiated treatment protocol. Improving therapeutic outcome and reducing complication rates are the major objectives. It will be essential to continue accumulating clinical data to further optimize the therapeutic strategy of personalized botulinum toxin type A injection for masseter hypertrophy.
Patients provided written consent for the use of their images.
1. Black MJ, Schloss MD. Masseteric muscle hypertrophy. J Otolaryngol. 1985;14:203–205
2. Moore AP, Wood GD. The medical management of masseteric hypertrophy with botulinum toxin type A. Br J Oral Maxillofac Surg. 1994;32:26–28
3. Rijsdijk BA, van ES RJ, Zonneveld FW, Steenks MH, Koole R. Botulinum toxin type A treatment of cosmetically disturbing masseteric hypertrophy (in Dutch). Ned Tijdschr Geneeskd. 1998;142:529–532
4. Carruthers J, Fagien S, Matarasso SLBotox Consensus Group. . Consensus recommendations on the use of botulinum toxin type a in facial aesthetics. Plast Reconstr Surg. 2004;114(Suppl):1S–22S
5. Kim NH, Chung JH, Park RH, Park JB. The use of botulinum toxin type A in aesthetic mandibular contouring. Plast Reconstr Surg. 2005;115:919–930
6. Chang CS, Bergeron L, Yu CC, Chen PK, Chen YR. Mandible changes evaluated by computed tomography following botulinum toxin A injections in square-faced patients. Aesthetic Plast Surg. 2011;35:452–455
7. Ahn J, Horn C, Blitzer A. Botulinum toxin for masseter reduction in Asian patients. Arch Facial Plast Surg. 2004;6:188–191
8. Choe SW, Cho WI, Lee CK, Seo SJ. Effects of botulinum toxin type A on contouring of the lower face. Dermatol Surg. 2005;31:502–507 discussion 507
9. Kwon JS, Kim ST, Jeon YM, Choi JH. Effect of botulinum toxin type A injection into human masseter muscle on stimulated parotid saliva flow rate. Int J Oral Maxillofac Surg. 2009;38:316–320
10. Gaofeng L, Jun T, Bo P, Bosheng Z, Qian Z, Dongping L. Evaluation and selecting indications for the treatment of improving facial morphology by masseteric injection of botulinum toxin type A. J Plast Reconstr Aesthet Surg. 2010;63:2026–2031
11. Jaspers GW, Pijpe J, Jansma J. The use of botulinum toxin type A in cosmetic facial procedures. Int J Oral Maxillofac Surg. 2011;40:127–133
12. Lee SJ, Kang JM, Kim YK, Park J, Kim do Y. Paradoxical bulging of muscle after injection of botulinum neurotoxin type A into hypertrophied masseter muscle. J Dermatol. 2012;39:804–805
13. To EW, Ahuja AT, Ho WS, et al. A prospective study of the effect of botulinum toxin A on masseteric muscle hypertrophy with ultrasonographic and electromyographic measurement. Br J Plast Surg. 2001;54:197–200
14. Wheeler A, Smith HS. Botulinum toxins: Mechanisms of action, antinociception and clinical applications. Toxicology. 2013;306:124–146
15. Hu KS, Kim ST, Hur MS, et al. Topography of the masseter muscle in relation to treatment with botulinum toxin type A. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010;110:167–171
16. Carruthers A, Carruthers J. Botulinum toxin type A. J Am Acad Dermatol. 2005;53:284–290
17. Kim DH, Hong HS, Won SY, et al. Intramuscular nerve distribution of the masseter muscle as a basis for botulinum toxin injection. J Craniofac Surg. 2010;21:588–591
18. Klein AW. Complications, adverse reactions, and insights with the use of botulinum toxin. Dermatol Surg. 2003;29:549–556 discussion 556