The Topographic Anatomy of the Masseteric Nerve: a Cadaveric Study with an Emphasis on the Effective Zone of Botulinum Toxin a Injections in Masseter B

Journal of Plastic, Reconstructive & Aesthetic Surgery (2014) 67, 1663e1668

The topographic anatomy of the masseteric nerve: A cadaveric study with an emphasis on the effective zone of botulinum toxin A injections in masseter B. Kaya a, N. Apaydin b,*, M. Loukas c, R.S. Tubbs d a Department of Plastic and Reconstructive Surgery, Ankara University Faculty of Medicine, Ankara, Turkey b Department of Anatomy, Ankara University Faculty of Medicine, Ankara, Turkey c Department of Anatomical Sciences, St. George’s University, St. George’s, Grenada d Pediatric Neurosurgery Children’s Hospital, Birmingham, AL, USA

Received 8 November 2013; accepted 29 July 2014

KEYWORDS Summary Introduction: Botulinum toxin injections are previously reported to be a noninva- Masseter muscle; sive alternative method for treating masseteric hypertrophy. However, there is a debate on Masseteric nerve; finding an ideal place for injection. The aim of this study is to document the anatomical land- Motor nerve entry marks for defining the motor nerve entry points (MNEPs) of the masseteric nerve in the point; masseter for effective botulinum toxin injections. Masseteric Materials and methods: Twelve sides from six adult fixed cadavers were used for this study. hypertrophy; The MNEPs of the masseteric nerve were defined according to standard landmark lines Botulinum toxin; including the orbitomeatal line (OML) and the line (VL), which intersects the mid-distance Facial reanimation of the OML to the tip of the angle of the mandible. Results: All MNEPs were located 4.4 cm inferior to the OML. In addition, the average anterior distance of the MNEPs to the VL was 1.4 cm and the average posterior distance was 0.6 cm. Conclusion: The ideal site of Botox injection into the masseter is a rectangular area: 5 cm inferior to the OML, 1 cm anterior and posterior to the VL, and just above the periosteum. Based on the data of our study, injections to the parotid gland and branches of the facial nerve such as the marginal mandibular and buccal can be avoided. The masseteric nerve can easily be found

* Corresponding author. Ankara University Faculty of Medicine, Department of Anatomy, 06100 Sihhiye, Ankara, Turkey. Tel.: þ90 312 5958248, þ90 312 3103010x246; fax: þ90 312 3105001. E-mail address: [email protected] (N.Apaydin). http://dx.doi.org/10.1016/j.bjps.2014.07.043 1748-6815/ª 2014 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved. 1664 B. Kaya et al.

approximately 1.0e1.5 cm inferior to the zygomatic arch, 1 cm medial to the temporomandibular joint capsule, and 1 cm superior to mandibular notch, which makes its use for facial reanimations more efﬁcient. ª 2014 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Introduction Materials and methods

The masseter is one of the four principal muscles of Twelve sides from six adult fixed cadavers were used for mastication which covers the angle of the mandible and this study. Of these, four were male and two were female mandibular ramus. Its main function is elevation of the and ranged in age from 56 to 69 years (mean 63 years) at mandible and it has a small effect on side-to-side move- death. None of the cadavers showed any gross pathology or ments.1 It also has an important morphological role in signs of surgical procedures in the examined area. Each delineating the lower facial contour, which is aesthetically cadaver was placed prone and the skin and the subcu- important.2 Masseteric hypertrophy is a rare disorder that taneous tissue over the masseter were cut and removed may present as either a unilateral or bilateral swelling in completely. The branches of the facial nerve were carefully the region of the angle and the ramus of the mandible. preserved. Patient complaints are usually aesthetic in nature, but Using a surgical microscope, the masseteric nerve was there may also be pain in the region and limitation of mouth exposed at the mandibular notch and its branches were opening.3,4 followed to its entrance into the masseter muscle. The The surgical treatment of this anomaly involves resec- dorsal part of the inferior attachment of the muscle to the tion of a portion of the masseter muscle.5 However, there mandible was detached in order to observe the entry site of are several complications associated with surgery. These each branch. complications include severe bleeding, hematoma, pro- The masseteric nerve and distribution of its branches longed edema, facial nerve injury, trismus, and bad scar- were determined in reference to the following bony ring. To avoid these complications, noninvasive modalities landmarks such as occlusal adjustment, splint therapy, tranquilizers, and antidepressants have been used for treatment.6 Botu- linum toxin type A (BTX-A) injection is an alternative, Determination of the origin of the masseteric nerve relatively noninvasive, and effective treatment for through the mandibular notch masseter muscle hypertrophy.7e9 BTX-A is a potent bacterial neurotoxin produced by an The closest distances between the origin of the nerve anaerobic bacterium Clostridium botulinum. It causes through the mandibular notch to the most medial part of muscle paralysis, atrophy, and weakness by chemical the temporomandibular joint (TMJ), zygomatic arch, and denervation. In muscle, it blocks the neuromuscular mandibular notch were measured. The TMJ landmark was transmission through rapid and strong attachment to the located on the medial surface of the mandibular condyle. In presynaptic nerve membrane. It inhibits the release of addition, the measurements concerning the mandibular vesicle-bound acetylcholine at the neuromuscular notch were made on its distal edge. junction.10 Previous studies indicate the importance of defining the motor nerve entry points (MNEPs) of a muscle for an Determination of the distribution of the branches e effective, selective, and safe BTX injection.7,11 13 In 2010, of the masseteric nerve Hu et al.6 established the safest injection sites for BTX injection into the masseter muscle by a well-designed study. The number of branches of the masseteric nerve at the They showed that the safest injection point is the central level of the mandibular notch, as well as the MNEPs of each compartment of the muscle so as to avoid injections into nerve branch, was recorded. Next, the MNEPs were defined the parotid gland or into the marginal mandibular branch of according to standard landmark lines. These standard lines the facial nerve; however, they did not investigate the included the orbitomeatal line (OML) and the line (VL) MNEPs to the muscle. which intersects the mid-distance of the OML to the tip of There are numerous studies targeting the different the angle of the mandible. The OML was classically deter- 13,14 muscles in the body investigating MNEPs ; however, mined as the line that connects the lateral palpebral theMNEPsofthemassetermusclehavenotbeenwell commissure to the tragus. The distance of each motor entry defined according to standard anatomical landmarks. The point of masseter nerve branches to these lines was aim of this study, therefore, is to document the anatom- measured by taking the OML as X and the VL as Y landmark ical landmarks for defining the MNEPs of the masseteric lines. These landmark lines were expressed in absolute nerve in the masseter for effective botulinum toxin distances, and based on the Y landmark line, the region injections. anterior to it was determined as the (þ) Y landmark line The topographic anatomy of the masseteric nerve 1665 while the region posterior to it was () Y landmark line (Figure 1). All measurements were carried out using digital calipers (Vernier LCD Digital Caliper Measuring, USA). In order to correct for individual examiner variability, each specimen was examined by two members of the team (BK, NA). Each observer made single independent measurements and the mean of all measurements was recorded.

Results

The masseteric nerve was observed to travel through the mandibular notch in all cases. The nerve and its motor branches coursed just above the periosteum in the majority of the specimens (eight cases) and it traveled between the superficial and deep layers of the masseter in the remaining specimens (four cases). The branches of the masseteric nerve were accompanied by branches of the masseteric artery and had no close relation with other nerve branches. The origin of the nerve through the mandibular notch was 13.8 4.5 mm inferior to the zygomatic arch, 10.6 2.7 mm medial to the TMJ capsule, and 7.8 2.0 mm superior to the mandibular notch (Figure 2). The mean length of the OML was measured as 8.4 1.8 cm and the VL as 8.6 1.5 cm. There were three to seven branches (mean five) of the masseteric nerve separately innervating the deep and superficial layers of

Figure 2 Figure showing the determination of the origin of the masseteric nerve through the mandibular notch (asterisk). The closest distances between the origin of the nerve through the mandibular notch to the most medial part of the temporomandibular joint (TMJ), zygomatic arch, and mandibular notch (notch) were measured.

the masseter. It was also observed in all cases that the upper half of the muscle mass received more ﬁbers than the lower half of the muscle. The evaluation of the location of the MNEPs showed that all MNEPs were located inferior to the OML (X landmark line). The average distance on the X landmark line for all regions of the MNEPs was 4.4 cm (minimum: 3.1 cm, maximum: 7.5 cm). The average distance of the MNEPs on the (þ) Y landmark line was measured to be 1.4 cm (minimum: 1.3 cm, maximum: 2.0 cm) whereas on the ()Y landmark line, the average distance was 0.6 cm (minimum: 0.2 cm, maximum: 1.1 cm) (Figure 3).

Discussion

BTX-A is commonly used for treating a variety of neuromuscular disorders such as strabismus, blepharospasm, Figure 1 Figure showing the reference line from the lateral hemifacial spasm, and torticollis.13,15 It has also been used palpebral commissure to the tragus, namely, the OML and the as a noninvasive treatment for patients with masseteric line (VL) which intersects the mid-distance of the OML to the hypertrophy.8,9 The anatomy of the masseter muscle has tip of the angle of mandible. Based on these reference lines, been well deﬁned in classical anatomy textbooks1 and in the OML was determined as the X landmark line and the VL as recent reports.2 However, the innervation patterns and the the Y landmark line. The region anterior to it was determined distribution of nerve branches into the muscle are not well as the (þ) Y landmark line while the region posterior to it was investigated. Hence, there is still debate in determining the the () Y landmark line. ideal site of injection into the masseter muscle. 1666 B. Kaya et al.

upper four compartments and areas II, IV, VI, and VIII were assigned to represent the lower four compartments. The center of compartment VI was suggested to be the safest and most efficient injection site for BTX-A into the masseter muscle to avoid injury to the parotid gland, which usually occupies compartments I and II, and the marginal mandibular branch of the facial nerve, which was located a mean of 7.4 mm superior to the inferior mandibular margin. Although this study provided information about the location of the nerve branches with respect to the structures that should be avoided during injection, the exact locations of MNEPs were not defined. Additionally, as the patients have masseteric hypertrophy, the compartmentalization of the muscle mass may not be standardized for each individual. We suggest that defining standard anatomical landmarks, which is not dependent on personal characteristics, is mandatory. The exact localization of MNEPs of the masseteric nerve has been investigated by Kim et al.18 These authors dissected twelve masseter muscles and observed the innervation pattern of masseteric nerve in the superficial, middle, and deep layers of the muscle. They also divided the muscle into compartments and investigated the distribution of the nerve branches in different compartments. They used the anterior margin of the middle layer of the muscle as a reference, and according to this reference point, they divided the masseteric nerve into four groups: posterosuperior, posteroinferior, anterosuperior, and anteroinferior. Although they were able to show the Figure 3 Figure showing the determination of the distribu- innervation patterns in each segment and revealed that the tion of the branches of the masseteric nerve. There are three masseteric nerve branches were mostly confined to the motor branches (arrowheads) seen in this figure; all are located lower middle third of the whole masseter muscle, they did below the X landmark line (orbitomeatal line) and on the (þ)Y not suggest an ideal place for injection of the muscle. landmark line. The superficial and deep layers of the masseter In this study, we defined standard and easily definable and the point of nerve origin through the mandibular notch are anatomical landmarks including the OML and the line (VL), also marked on the figure. which intersects the mid-distance of the OML to the tip of the angle of the mandible. These lines can be used for exact localization of the injection point of BTX-A into the Cotrufo et al.16 have revealed a “masseteric area” muscle. As these references are individually based, we where the main trunk of the masseteric nerve can be easily suggest that they can be used reliably in any patient. These defined. Thus, they have suggested an optimized technique reference lines can be considered as X and Y landmark lines of harvesting it as a donor nerve for facial reanimation. The as was defined previously by Lee et al.13 for the sterno- branching pattern of the masseteric nerve has also been cleidomastoid muscle. Accordingly, our results revealed investigated by Brenner and Schoeller,17 and it was that all MNEPs were located 4.4 cm (minimum: 3.1 cm, revealed that the masseteric nerve may have variant maximum: 7.5 cm) below the OML (X landmark line). The numbers of branches after leaving the infratemporal fossa. average distance of the MNEPs on the (þ) Y landmark line Although our anatomical landmarks are different, we also was 1.4 cm (minimum: 1.3 cm, maximum: 2.0 cm) whereas suggest that the main trunk of the masseteric nerve can be on the () Y landmark line, it was 0.6 cm (minimum: found in a so-called “masseteric area” which is located 0.2 cm, maximum: 1.1 cm). These results were addressing 13.8 4.5 mm inferior to the zygomatic arch, the ideal site of Botox injection into the masseter is an 10.6 2.7 mm medial to the temporomandibular joint area, approximately 5 cm inferior to the OML (minimum: capsule, and 7.8 2.0 mm superior to the mandibular 3.1 cm, maximum: 7.5 cm), 1 cm anterior and posterior to notch. the VL (Figure 4). This location can also be considered as Previous studies have attempted to define an ideal site the half distance of the VL. This region was free of the of BTX-A injection to the masseter. Injection into the parotid gland, marginal mandibular nerve, and other muscle was first defined by von Lindern et al.7 and the in- branches of the facial nerve such as its buccal branch. jection was suggested to be applied on part of the zygo- Once BTX is injected into the muscle, it is known to matic arch and mandibular angle. However, this method immediately diffuse into the muscle within a few centi- was associated with the risk of invading the parotid gland. meters of the needle tip. When a higher volume is injected, In a study by Hu et al.,6 the surface of the masseter was the area of diffusion seems to increase; however, inaccu- compartmentalized into eight areas and numbered from I to rate injection and excessive diffusion of the toxin can lead VIII. Areas I, III, V, and VII were assigned to represent the to systemic adverse effects or unwanted weakness of the The topographic anatomy of the masseteric nerve 1667

masseteric nerve can easily be found approximately 1.0e1.5 cm inferior to the zygomatic arch, 1 cm medial to the TMJ capsule and 1 cm superior to the mandibular notch which makes its use for facial reanimations more efficient. The masseter muscle has significant applications for head and neck reconstruction and for muscle transposition flap for facial nerve paralysis.26e28 Therefore, it is important to know the course and the location of branches of the masseteric nerve in relation to standard anatomical landmarks not only for BTX injections but also to provide a safe and efficient approach for these applications. Hontanilla and Qui27 had reported a constant course with a distribution pattern that shows a tree-like anatomy in six cadavers. Hwang et al.28 examined the course of the masseteric nerve in relation to the masseteric muscle and found that the nerve ran anteriorly and inferiorly between the deep and the middle layers. The nerve was observed at 33 5.6 mm from the inferior border of the muscle on the anterior third vertical line of the masseter muscle and at 47 5.5 mm in the posterior third. The results of our study also revealed that the nerve was coursing between the superficial and deep layers of the muscle. However, we found its motor branches to distribute widely among muscle fibers and the Figure 4 Figure demonstrating the position of the injection. upper half of the muscle mass received more fibers than the OML: orbitomeatal line; VL: vertical line which intersects the lower half of the muscle. mid-distance of the OML to the tip of the angle of mandible, The limitation of this study is the fact that it is an gray square: suggested position of injection. experimental study conducted on cadavers. All cadaver studies have the limitation that it is difficult to reproduce. However, a clinical study would need to be undertaken to neighboring muscles.18,19 We suggest that a single injection properly determine the effects of this procedure. to an ideal site would be enough for diffusion of the toxin through MNEPs of other branches, and thus systemic adverse effects or unwanted weakness of neighboring Conclusion muscles may avoided. Concerning the dosage, there is no standardized dose of BTX-A for effective treatment of According to the results of our study, the ideal site of Botox masseteric hypertrophy. Although Lee et al.20 have stated injection into the masseter is a rectangular area, 5 cm that 30 IU BTX-A injection is effective for masseteric hy- inferior to the OML, 1 cm anterior and posterior to the VL, pertrophy, Kim et al.21 had proposed that >30 IU BTX-A may and just above the periosteum. These landmarks will avoid be required to achieve an adequate result. In addition to injection into the parotid gland, marginal mandibular this, Andrade and Deshpande22 have stated they had suc- nerve, and other branches of the facial nerve such as its cessfully managed masseter muscle hypertrophy by buccal branch. We also suggest that the masseteric nerve e injecting 40 IU of BTX-A. can easily be found approximately 1.0 1.5 cm inferior to The branches of the masseteric nerve are increasingly the zygomatic arch, 1 cm medial to the TMJ capsule and being used for facial reanimation procedures.17 However, it 1 cm superior to mandibular notch which makes its use for may not always be very easy to locate the nerve due to a facial reanimations more efficient. variety of described branching patterns and variability of facial measurements on which some surgical approaches Conflict of interest are based upon. Borschel et al.23 have studied the relation of the masseteric nerve to some surgical landmarks such as The authors declare that there is no conflict of interest. the auricular tragus and the zygomatic arch on eight cadavers and found the nerve to lie 3 cm anterior to the tragus at a level 1 cm inferior to the zygomatic arch. Collar References et al.24 dissected 10 cadavers and identified the masseteric nerve in the “subzygomatic triangle” which was formed by 1. Standring S. Head and neck. In: Standring S, editor. Gray’s the zygomatic arch superiorly, the TMJ posteriorly, and the anatomy. 40th ed. New York: Elsevier; 2008. p. 538. frontal branch of the facial nerve inferiorly and anteriorly. 2. Lee JY, Kim JN, Yoo JY, et al. Topographic anatomy of the Cheng et al.25 presented a technique to identify the nerve masseter muscle focusing on the tendinous digitation. Clin Anat 2012;25:889e92. in a 1.5 cm2 area defined by constant anatomical landmarks 3. Roncevic R. Masseter muscle hypertrophy. Aetiology and such as the zygomatic arch, condyle, coronoid process, and therapy. J Maxillofac Surg 1986;14:344e8. mandibular notch. Our study revealed that the nerve was 4. Tabrizi R, Ozkan BT, Zare S. Correction of lower facial wideness 1.4 cm inferior to the zygomatic arch, which is consistent due to masseter hypertrophy. J Craniofac Surg 2010;21: with these studies. Therefore, we also suggest that the 1096e7. 1668 B. Kaya et al.

5. Kim SK, Han JJ, Kim JT. Classiﬁcation and treatment of and clinical study. J Plast Reconstr Aesthet Surg 2011;64: prominent mandibular angle. Aesthet Plast Surg 2001;25: 1424e9. 382e7. 17. Brenner E, Schoeller T. Masseteric nerve: a possible donor for 6. Hu KS, Kim ST, Hur MS, et al. Topography of the masseter facial nerve anastomosis? Clin Anat 1998;11:396e400. muscle in relation to treatment with botulinum toxin type A. 18. Kim DH, Hong HS, Won SY, et al. Intramuscular nerve distri- Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;110: bution of the masseter muscle as a basis for botulinum toxin 167e71. injection. J Craniofac Surg 2010;21:588e91. 7. von Lindern JJ, Niederhagen B, Apple T. Type A botulinum 19. Hsu TS, Dover JS, Arndt KA. Effect of volume and concentration toxin for the treatment of hypertrophy of the masseter and on the diffusion of botulinum exotoxin A. Arch Dermatol 2004; temporal muscles: an alternative treatment. Plast Reconstr 140:1351e4. Surg 2001;107:327e32. 20. Lee DH, Jin SP, Cho S, et al. RimabotulinumtoxinB versus 8. Castro WH, Gomez RS, Da Silva Oliveira J, Moura MD, onabotulinumtoxinA in the treatment of masseter hypertro- Gomez RS. Botulinum toxin type A in the management of phy: a 24-week double-blind randomized split-face study. masseter muscle hypertrophy. J Oral Maxillofac Surg 2005;63: Dermatology 2013;226:227e32. 20e4. 21. Kim HJ, Yum KW, Lee SS, Heo MS, Seo K. Effects of botulinum 9. Choe SW, Cho WI, Lee CK, Seo SJ. Effects of botulinum toxin toxin type A on bilateral masseteric hypertrophy evaluated type A on contouring of the lower face. Dermatol Surg 2005; with computed tomographic measurement. Dermatol Surg 31:502e7. 2003;29:484e9. 10. Schantz EJ, Johnson EA. Properties and use of botulinum toxin 22. Andrade NN, Deshpande GS. Use of botulinum toxin (botox) in and other microbial neurotoxins in medicine. Microbiol Rev the management of masseter muscle hypertrophy: a simpliﬁed 1992;56:80e99. technique. Plast Reconstr Surg 2011;128:24ee6e. 11. Collins A, Jankovic J. Botulinum toxin injection for congenital 23. Borschel GH, Kawamura DH, Kasukurthi R, Hunter DA, Zuker RM, muscular torticollis presenting in children and adults. Woo AS. The motor nerve to the masseter muscle: an anatomic Neurology 2006;67:1083e5. and histomorphometric study to facilitate its use in facial 12. Durazzo MD, Furlan JC, Teixeira GV, et al. Anatomic landmarks reanimation. J Plast Reconstr Aesthet Surg 2012;65:363e6. for localization of the spinal accessory nerve. Clin Anat 2009; 24. Collar RM, Byrne PJ, Boahene KD. Plast Reconstr Surg 2013;132: 22:471e5. 183e8. http://dx.doi.org/10.1097/PRS.0b013e318290f6dc. 13. Lee JH, Lee BN, Han SH, An XC, Chung RH. The effective zone 25. Cheng A, Audolfsson T, Rodriguez-Lorenzo A, Wong C, Rozen S. of botulinum toxin A injections in the sternocleidomastoid J Plast Reconstr Aesthet Surg 2013;66:1438e40. http: muscle. Surg Radiol Anat 2011;33:185e90. //dx.doi.org/10.1016/j.bjps.2013.04.009. 14. Apaydin N, Loukas M, Kendir S, et al. The precise localization 26. Manktelow RT, Tomat LR, Zuker RM, Chang M. Smile recon- of distal motor branches of the tibial nerve in the deep pos- struction in adults with free muscle transfer innervated by the terior compartment of the leg. Surg Radiol Anat 2008;30: masseter motor nerve: effectiveness and cerebral adaptation. 291e5. Plast Reconstr Surg 2006;118:885e99. 15. Traba Lopez A, Esteban A. Botulinum toxin in motor disorders: 27. Hontanilla B, Qiu SS. Transposition of the hemimasseteric practical considerations with emphasis on interventional muscle for dynamic rehabilitation of facial paralysis. J Cra- neurophysiology. Neurophysiol Clin 2001;31:220e9. niofac Surg 2012;23:203e5. 16. Cotrufo S, Hart A, Payne AP, Sjogren A, Lorenzo A, Morley S. 28. Hwang K, Kim YJ, Chung IH, Song YB. Course of the masseteric Topographic anatomy of the nerve to masseter: an anatomical nerve in masseter muscle. J Craniofac Surg 2005;16:197e200.