Research

Original Investigation

The Role of Botulinum Toxin A in the Establishment
of Symmetry in Pediatric Paralysis of the Lower Lip
Siba Haykal, MD, PhD; Ehud Arad, MD; Shaghayegh Bagher, MSc; Carolyn Lai, MD; Marc Hohman, MD;
Tessa Hadlock, MD; Ronald M. Zuker, MD, FRCSC; Gregory H. Borschel, MD

IMPORTANCE Botulinum toxin A has been described as an effective adjunct treatment for

Author Audio Interview at
jamafacialplasticsurgery.com

achieving symmetry in adults with facial paralysis. Few investigators have described the use
of botulinum toxin A in pediatric patients with facial paralysis.
OBJECTIVE To present our preliminary experience with botulinum toxin A in pediatric
patients presenting with asymmetry of the lower lip.
DESIGN, SETTING, AND PARTICIPANTS We performed a retrospective medical record review
of all pediatric patients (age range, 4-17 years; mean [SD] age, 11.2 [4.7] years) with facial
paralysis who were treated with botulinum toxin A injections from January 1, 2004,
through December 31, 2012. Patients presented for treatment at The Hospital for Sick
Children, Toronto, Ontario, Canada, or the Massachusetts Eye and Ear Infirmary,
Boston.
MAIN OUTCOMES AND MEASURES Using facial analysis software, we measured lower lip
asymmetry in the patients’ photographs before and after treatment, at rest, and in a dynamic
state. We performed analysis of variance to assess for improvement in symmetry.
RESULTS We identified 18 patients with the following 3 primary indications for treatment:
focal lip asymmetry (n = 11), extensive hemifacial asymmetry (n = 5), and focal synkinesis
(n = 2). We found no complications related to botulinum toxin A treatment. The mean (SD)
dynamic deviation before the injection was 3.5 (1.7) mm, whereas the mean dynamic
deviation after the injection was 1.5 (0.8) mm. The mean (SD) deviation correction was
evaluated at 61% (6%) and was statistically significant (P = .04).
CONCLUSIONS AND RELEVANCE Botulinum toxin A injection is a safe procedure for improving
localized asymmetry in pediatric patients with facial paralysis. Preliminary results indicate
that botulinum toxin A may be an effective treatment for lower lip asymmetry in children
and adolescents.

Corresponding Author: Siba Haykal,
MD, PhD, Division of Plastic and
Reconstructive Surgery, Department
of Surgery, University of Toronto, 111
Elizabeth St, Toronto, ON M5G 1P7,
Canada (siba.haykal@utoronto.ca).

LEVEL OF EVIDENCE 4.
JAMA Facial Plast Surg. doi:10.1001/jamafacial.2015.10
Published online March 5, 2015.

F

acial paralysis results in variable degrees of functional
deficits and aesthetic asymmetry. Severe cases of paralysis often require surgical reconstruction with nerve and
muscle transfers, whereas milder cases can be treated with digastric muscle transfer, sling suspension, or orbicularis advancement, which are not uniformly successful,1-3 or managed nonsurgically with physiotherapy and rehabilitation strategies. As
an adjunct to physiotherapy, botulinum toxin A, a neurotoxin
that prevents the release of acetylcholine, has been used for improvement of facial symmetry. Its purpose is the weakening of
strong muscles on the nonparalyzed side of the face.
jamafacialplasticsurgery.com

Author Affiliations: Division of
Plastic Surgery, The Hospital for Sick
Children, Toronto, Ontario, Canada
(Haykal, Bagher, Lai, Zuker, Borschel);
Division of Plastic and Reconstructive
Surgery, Department of Surgery,
University of Toronto, Toronto,
Ontario, Canada (Haykal, Bagher, Lai,
Zuker, Borschel); Department of
Plastic Surgery, Tel Aviv Sourasky
Medical Center, Tel Aviv, Israel (Arad);
Facial Nerve Center, Massachusetts
Eye and Ear Infirmary, Boston
(Hohman, Hadlock).

The use of botulinum toxin A for facial paralysis has been
described in adults4-12 and more specifically for protective ptosis in the treatment of lagophthalmos13 after iatrogenic nerve
injury14 and hyperlacrimation.15 Use of botulinum toxin A in
children is very limited, with one report of 11 pediatric patients treated for focal synkinesis after facial paralysis16 and
another report of treatment of lower lip asymmetry that included some pediatric patients.17 The purpose of this study was
to examine the use of botulinum toxin A in children with facial paralysis, focusing on indications, technique, and rate of
complications.
(Reprinted) JAMA Facial Plastic Surgery Published online March 5, 2015

Copyright 2015 American Medical Association. All rights reserved.

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and G. 2012. Measurement of Facial Symmetry The facial analysis software developed by the MEEI has been validated for measuring facial symmetry. the mentalis. and platysma.0-25. extensive hemifacial asymmetry (n = 5). and inferoposterior aspects. characteristics of facial paralysis.3. Boston.com/ by a Karolinska Institutet University Library User on 03/19/2015 jamafacialplasticsurgery. Written informed consent was obtained from the patients or a family member. tient. version 9.H.H. superoposterior.).18 We used the software to measure the difference in vertical aperture between the paralyzed and nonparalyzed sides of the lip. Two of these patients had been treated with nerve cable grafts after trauma and tumor resection. the depressors (mainly depressor labii inferioris and anguli oris). All rights reserved.Research Original Investigation Botulinum Toxin A in Lower Lip Paralysis Table 1. All 3 patients were treated with botulinum toxin A for focal lip asymmetry. Five patients had undergone reconstructive surgery for facial paralysis before botulinum toxin A treatment. Demographic patient data are summarized in Table 2.2 [4. at locations best correlating with muscles causing the greatest degree of asymmetry. Injection sites were marked before administration of anesthesia. 2015 (Reprinted) Copyright 2015 American Medical Association. green circle. Injection Technique Injection of botulinum toxin A was performed under deep sedation or general anesthesia in patients younger than 10 years and with no anesthesia for older patients.0 Platysma 10. JAMA Facial Plastic Surgery Published online March 5. Downloaded From: http://archfaci. and focal synkinesis (n = 2).M. Fourteen patients were female and 4 were male. mentalis. Statistical Analysis Values of lip deviation before and after botulinum toxin A injections (at rest and while smiling) were compared across evaluations by repeated-measures analysis of variance using commercially available software (PROC-Mixed SAS. Depressor or levator muscles of the lip were injected at the points causing maximum depression or elevation of the lip. Data included demographic information. Patients ranged in age from 4 to 17 years (mean [SD] age.com . The platysma is usually divided into anterosuperior. Demonstration of Botulinum Toxin A Injection Sites Botulinum Toxin A Administered. Toronto. For each paE2 Results We included 18 patients in this study.0-12. and the platysma.0 Lip depressors 10. a physiotherapist. which was defined as the lip deviation in each photograph. orange circle. Data Collection The inclusion criteria consisted of all patients younger than 18 years with facial paralysis who were treated with botulinum toxin A and had a minimum of 2 years of follow-up after the last injection. anteroinferior.0 Methods Patient Selection We obtained approval from the research ethics boards of The Hospital for Sick Children. Three additional patients had been treated with a gracilis muscle transfer (as a 1-stage procedure with coaptation to the masseteric nerve in 1 patient and as a 2-stage procedure after facial nerve cross-graft in 2 patients). surgical procedures.Z. Canada. We performed a retrospective review of health records for all patients with facial paralysis who had been treated with botulinum toxin A in our institutions from January 1. information pertaining to botulinum toxin A injections (doses. number of injections. and injection sites are shown in Figure 1. 2004.) or an earnose-throat surgeon (T. SAS Institute Inc). Doses of botulinum toxin A that were used for each muscle are summarized in Table 1. and the Massachusetts Eye and Ear Infirmary (MEEI). purple circles.jamanetwork. and an occupational therapist. The location of injection of the superolateral and inferolateral orbicularis occuli is demonstrated as blue circles. Site and Amount of Botulinum Toxin A Injection Site of Injection Figure 1. Both patients had residual hemifacial asymmetry and focal synkinesis and were treated with botulinum toxin A injections to the orbicularis oculi.7] years). U Orbicularis oculi 7.5-10. A multidisciplinary team approach was involved in the treatment of these patients. and time intervals).0-15. injection points were marked over synkinetic muscles at areas with the most prominent synkinetic contractions and least risk for functional impairment. outcomes were determined by the change in lip deviation before and after botulinum toxin A injection (Figure 2). Ontario. The 3 primary indications for treatment were focal lip asymmetry (n = 11). The team included a plastic surgeon (R. Statistical significance was determined as P < . through December 31. and reported complications. For treatment of focal synkinesis. lip depressors.B.05.0 Mentalis 5. 11. Injection sites were prepared with isopropyl alcohol.

5 (0.com/ by a Karolinska Institutet University Library User on 03/19/2015 E3 . The botulinum toxin A injection data by indication group is summarized in Table 3. Representative Photographs of Lip Symmetry Analysis A Before Treatment C B After Treatment D After Treatment Before Treatment We used facial symmetry analysis software with repeated-measures analysis of variance.jamanetwork. Summary of Patient Characteristicsa Characteristic Data Age at presentation.Botulinum Toxin A in Lower Lip Paralysis Original Investigation Research Figure 2. During a minimum of 2 years from the last injection. The mean (SD) dynamic deviation before the injection was 3. whereas the mean (SD) dynamic deviation after the injection was 1. The lower lip difference was measured before (A and C) and after (B and D) botulinum toxin A treatment. The 11 patients treated for focal lip asymmetry had a mean of 3. A standardized protocol has also been established to provide physicians with management techniques to improve patient satisfaction and to offer physicians and patients insight into the likely outcome. Cause of paralysis Acquired Congenital a 11 7 Unless otherwise indicated.com Discussion Asymmetry of the lower lip secondary to facial nerve dysfunction presents with challenging considerations. We used the MEEI facial analysis software for evaluation of the deviation correction before and after botulinum toxin A injection.4 for the 5 patients in the hemifacial group and 7. All rights reserved. Downloaded From: http://archfaci. multiple studies have shown that (Reprinted) JAMA Facial Plastic Surgery Published online March 5.7) [4-17] Sex Male Female 4 14 Laterality of paralysis Right 7 Left 10 Bilateral 1 months.3 for the 2 patients in the focal synkinesis group. Several different techniques have been postulated to regain symmetry. 2015 Copyright 2015 American Medical Association.2 (4. mean (SD) [range]. data are expressed as number of patients. The deviation correction was evaluated at a mean (SD) of 61% (6%) and was statistically significant (P = .04).5 (1. The median time between botulinum toxin A treatments was 4 jamafacialplasticsurgery.8) mm. including surgical and nonsurgical approaches.17 Thus.6 botulinum toxin A treatments compared with 8. y 11.7) mm. Table 2. no patients experienced complications attributed to botulinum toxin A. Two of the patients treated for focal lip asymmetry underwent subsequent myectomy.

Critical revision of the manuscript for important intellectual content: All authors. Arad. Plast Reconstr Surg. Bulstrode NW. Terzis et al16 studied 11 pediatric patients presenting with focal synkinesis after facial paralysis and compared facial nerve crossgrafting and secondary microcoaptations with direct muscle neurotization with or without botulinum toxin A injection. Arad. Plast Reconstr Surg. We have also shown that botulinum toxin A did not result in any complications during a minimum of 2 years from the last injection. Saeed S.22 As such and knowing the potential for plasticity. Hadlock. Studies have established the associated quality-of-life benefit and reaffirmed its important role in the multimodality management of facial nerve disorders. Borschel. Sadiq S. 3. Furthermore. 6.73(11):1431-1436. which is a limitation of this study. Plast Reconstr Surg. our patients continued to show symmetrical results in follow-up. Drafting of the manuscript: Haykal. of patients 2 0 0 botulinum toxin A has a well-established objective benefit in the control of facial hyperkinesis in patients with facial nerve disorders. 2015 (Reprinted) Copyright 2015 American Medical Association.19 Botulinum toxin A is injected to the normal side to weaken it.3 (3-15) Time between injections. or material support: Haykal. Borodic G. Arad. Study concept and design: Arad. thus allowing the weaker affected side to overcome the effect of the contralateral normal muscle and provide a more symmetrical smile. All rights reserved. Tomat LR. and has a potential for restoration of permanent symmetry. 2015. Borschel. de Maio M. The authors concluded that facial nerve cross-grafting with botulinum toxin A injection was effective despite having only 2 patients treated in that group and a total of 4 pediatric patients receiving botulinum toxin A treatment. and 2 patients with focal synkinesis. a ing facial symmetry.116 (1):36-43. Zuker. our patient population included 11 patients treated for focal lip asymmetry.jamanetwork. Conflict of Interest Disclosures: None reported. 2003. Bento RF. Despite the numerous studies showing a benefit of botulinum toxin A in the adult population. Borschel. 5. which has been validated for measur- No patients experienced complications attributed to botulinum toxin A. Administrative.120(1):238-244.com . Depressor labii inferioris resection: an effective treatment for marginal mandibular nerve paralysis. 2. Bagher. Khwaja S. No. 2014. de Maio M. Borschel. is safe. A simple reconstruction for congenital unilateral lower lip palsy. doi:10. Author Contributions: Drs Haykal and Borschel had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. As such.105(6): 1917-1934. mean (range) 3. of patients Hemifacial Asymmetry (n = 5) 3 No. Shimizu S.115(6):1466-1471. 7. We have shown that botulinum toxin A significantly improves symmetry of the lower lip. 9. et al. Terzis JK. Microsurgical strategies in 74 patients for restoration of dynamic depressor muscle mechanism: a neglected target in facial reanimation.20 can promote better permanent symmetry21 through the creation of new motor patterns as a result of central motor learning. 2007. 8. Arad. This study represents the largest pediatric population. A total of 18 patients were included from The Hospital for Sick Children and the MEEI.21(1):15-20.Research Original Investigation Botulinum Toxin A in Lower Lip Paralysis Table 3. ARTICLE INFORMATION Published Online: March 5.10. Study supervision: Arad. Armstrong MW. 2007. Botulinum toxin for aberrant facial nerve regeneration: 10. Borschel. Br J Plast Surg. Manktelow RT. Lai. Plast Reconstr Surg. Botulinum toxin to improve lower facial symmetry in facial nerve palsy. double-blind.2015. 5 patients with extensive hemifacial asymmetry. These patients will require long-term follow-up to determine permanency of the symmetry. REFERENCES Accepted for Publication: December 30. we used the MEEI facial analysis software. median (range). Slattery W. Murray JA. Botulinum Toxin A Injection Data by Indication Groupsa Indication Lip Asymmetry (n = 11) Patient Characteristic Reanimation procedure before injection. Botulinum toxin in facial palsy: an effective treatment for contralateral hyperkinesis. very few studies have considered its role in the pediatric population. Statistical analysis: Haykal. Clin Otolaryngol Allied Sci. 2004.57(6):502-510. No.com/ by a Karolinska Institutet University Library User on 03/19/2015 jamafacialplasticsurgery. Zuker. especially when used in conjunction with physiotherapy. Mountain RE. Downloaded From: http://archfaci. Udagawa A. treated with botulinum toxin A. Moreover. Treatment of facial synkinesis and facial asymmetry with botulinum toxin type A following facial nerve palsy. The phenomenon of the late recovered Bell’s palsy: treatment options to improve facial symmetry. J Cosmet Laser Ther.4 (2-23) 0 7. Kalantarian B. 4. Arikawa K.120(7):1859-1864. Hussain G. Conclusions Botulinum toxin A injection represents an important adjunct therapy in the reestablishment of symmetry in the pediatric patient population with facial paralysis. some investigators believe that botulinum toxin A. technical. placebo-controlled trial using subjective endpoints. Hadlock. Bartley M. 1. Plast Reconstr Surg. analysis. Plast Reconstr Surg. Unlike those of previous studies. Bagher. Tang Y-B. E4 Focal Synkinesis (n = 2) JAMA Facial Plastic Surgery Published online March 5. the introduction of this treatment in the pediatric population can prove to be more beneficial. Hohman. 1996. Harrison DH. 2005. Bagher. Acquisition. 2005.5(3-4): 216-217.18 to quantify the difference in vertical aperture between the paralyzed and nonparalyzed sides of the lip and found significant differences before and after botulinum toxin A injections with a 61% correction. mo 4 (2-15) 4 (3-6) 4 (2-15) Subsequent myectomy. Use of botulinum toxin in facial paralysis. et al.1001/jamafacial. of injections.6 (1-8) 2 8. which gives insight into a potential mechanism of action and its important role in the pediatric population. or interpretation of data: Haykal.120(4): 917-927. Eye (Lond). 2012. 2007. Chen C-K. Myectomy and botulinum toxin for paralysis of the marginal mandibular branch of the facial nerve: a series of 76 cases. 2000. to our knowledge.

16. 15. Karypidis D.28(4):256-260. Urban LS. 21. Acta Otolaryngol. Comprehensive facial rehabilitation improves function in people with facial paralysis: a 5-year experience at the Massachusetts Eye and Ear Infirmary. Otol Neurotol.14(4): 277-282.jamanetwork.90(3):391-397. Boroojerdi B.32(1):1-7. Aesthetic indications for botulinum toxin injection. 19. Combined protocol for treatment of secondary effects from facial nerve palsy. automated facial measurement tool in facial reanimation. Rho SH. 2013. 2011. (Reprinted) JAMA Facial Plastic Surgery Published online March 5. All rights reserved. 2011.66(8):1058-1063. Botulinum toxin treatment of synkinesia jamafacialplasticsurgery. J Plast Reconstr Aesthet Surg. 13. A systematic algorithm for the management of lower lip asymmetry. Kim J. Edwards C.65(1):111-114.25(1):15-23. Huddleston SW.65(8): 1009-1018. 1994. Ferbert A.com Original Investigation Research and hyperlacrimation after facial palsy. Plast Reconstr Surg. Lee JM. Park SY. 14. Smitson C. Biagini M. 2014. Irintchev A. Arch Facial Plast Surg. 12. Botulinum toxin injection of both sides of the face to treat post-paralytic facial synkinesis. Contralateral botulinum toxin injection to improve facial asymmetry after acute facial paralysis. Downloaded From: http://archfaci. Neiss WF. Botulinum toxin-A–induced protective ptosis in the treatment of lagophthalmos associated with facial paralysis.Botulinum Toxin A in Lower Lip Paralysis 11. 2013. Yücel OE. Lindsay RW. 2012.10(2):84-87. Ophthalmol Plast Reconstr Surg. 2012. Monini S. 1998. Noth J. Botulinum toxin and quality of life in patients with facial paralysis. Herath H. Guyuron B.com/ by a Karolinska Institutet University Library User on 03/19/2015 E5 . Terzis JK. Jeon JH. et al. Robinson M. Hadlock TA. 20. J Neurol Neurosurg Psychiatry. Cheney ML. 18. Angelov DN.34(2):319-324.131(8): 882-886. Am J Otolaryngol. Schwarz M. Hadlock T. Artürk N. Toward a universal. 2012. Guntinas-Lichius O. Hadlock T. Improved functional recovery after facial nerve reconstruction by temporary denervation of the contralateral mimic musculature with botulinum toxin in rats. De Carlo A. Hadlock TA. Neurorehabil Neural Repair. Glowka TR. 17. Choi KH. Phys Ther. J Plast Reconstr Aesthet Surg. Therapeutic strategies in post-facial paralysis synkinesis in pediatric patients. 2015 Copyright 2015 American Medical Association. 22. 2011. Kim J. Lindsay RW.93(5):913-918. Mehta RP. 2010.