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Figure 1.
Demonstration of Botulinum Toxin A Injection Sites
Demonstration of Botulinum Toxin A Injection Sites

The location of injection of the superolateral and inferolateral orbicularis occuli is demonstrated as blue circles; the depressors (mainly depressor labii inferioris and anguli oris), orange circle; the mentalis, green circle; and the platysma, purple circles. The platysma is usually divided into anterosuperior, anteroinferior, superoposterior, and inferoposterior aspects.

Figure 2.
Representative Photographs of Lip Symmetry Analysis
Representative Photographs of Lip Symmetry Analysis

We used facial symmetry analysis software with repeated-measures analysis of variance. The lower lip difference was measured before (A and C) and after (B and D) botulinum toxin A treatment.

Table 1.  
Site and Amount of Botulinum Toxin A Injection
Site and Amount of Botulinum Toxin A Injection
Table 2.  
Summary of Patient Characteristicsa
Summary of Patient Characteristicsa
Table 3.  
Botulinum Toxin A Injection Data by Indication Groupsa
Botulinum Toxin A Injection Data by Indication Groupsa
1.
Terzis  JK, Kalantarian  B.  Microsurgical strategies in 74 patients for restoration of dynamic depressor muscle mechanism : a neglected target in facial reanimation. Plast Reconstr Surg. 2000;105(6):1917-1934.
PubMedArticle
2.
Hussain  G, Manktelow  RT, Tomat  LR.  Depressor labii inferioris resection: an effective treatment for marginal mandibular nerve paralysis. Br J Plast Surg. 2004;57(6):502-510.
PubMedArticle
3.
Udagawa  A, Arikawa  K, Shimizu  S,  et al.  A simple reconstruction for congenital unilateral lower lip palsy. Plast Reconstr Surg. 2007;120(1):238-244.
PubMedArticle
4.
Armstrong  MW, Mountain  RE, Murray  JA.  Treatment of facial synkinesis and facial asymmetry with botulinum toxin type A following facial nerve palsy. Clin Otolaryngol Allied Sci. 1996;21(1):15-20.
PubMedArticle
5.
Borodic  G, Bartley  M, Slattery  W,  et al.  Botulinum toxin for aberrant facial nerve regeneration: double-blind, placebo-controlled trial using subjective endpoints. Plast Reconstr Surg. 2005;116(1):36-43.
PubMedArticle
6.
Sadiq  S, Khwaja  S, Saeed  S.  Botulinum toxin to improve lower facial symmetry in facial nerve palsy. Eye (Lond). 2012;73(11):1431-1436.
PubMedArticle
7.
de Maio  M.  Use of botulinum toxin in facial paralysis. J Cosmet Laser Ther. 2003;5(3-4):216-217.
PubMedArticle
8.
Chen  C-K, Tang  Y-B.  Myectomy and botulinum toxin for paralysis of the marginal mandibular branch of the facial nerve: a series of 76 cases. Plast Reconstr Surg. 2007;120(7):1859-1864.
PubMedArticle
9.
de Maio  M, Bento  RF.  Botulinum toxin in facial palsy: an effective treatment for contralateral hyperkinesis. Plast Reconstr Surg. 2007;120(4):917-927.
PubMedArticle
10.
Bulstrode  NW, Harrison  DH.  The phenomenon of the late recovered Bell’s palsy: treatment options to improve facial symmetry. Plast Reconstr Surg. 2005;115(6):1466-1471.
PubMedArticle
11.
Choi  KH, Rho  SH, Lee  JM, Jeon  JH, Park  SY, Kim  J.  Botulinum toxin injection of both sides of the face to treat post-paralytic facial synkinesis. J Plast Reconstr Aesthet Surg. 2013;66(8):1058-1063.
PubMedArticle
12.
Kim  J.  Contralateral botulinum toxin injection to improve facial asymmetry after acute facial paralysis. Otol Neurotol. 2013;34(2):319-324.
PubMedArticle
13.
Yücel  OE, Artürk  N.  Botulinum toxin-A–induced protective ptosis in the treatment of lagophthalmos associated with facial paralysis. Ophthalmol Plast Reconstr Surg. 2012;28(4):256-260.
PubMedArticle
14.
Guyuron  B, Huddleston  SW.  Aesthetic indications for botulinum toxin injection. Plast Reconstr Surg. 1994;93(5):913-918.
PubMedArticle
15.
Boroojerdi  B, Ferbert  A, Schwarz  M, Herath  H, Noth  J.  Botulinum toxin treatment of synkinesia and hyperlacrimation after facial palsy. J Neurol Neurosurg Psychiatry. 1998;65(1):111-114.
PubMedArticle
16.
Terzis  JK, Karypidis  D.  Therapeutic strategies in post-facial paralysis synkinesis in pediatric patients. J Plast Reconstr Aesthet Surg. 2012;65(8):1009-1018.
PubMedArticle
17.
Lindsay  RW, Edwards  C, Smitson  C, Cheney  ML, Hadlock  T.  A systematic algorithm for the management of lower lip asymmetry. Am J Otolaryngol. 2011;32(1):1-7.
PubMedArticle
18.
Hadlock  TA, Urban  LS.  Toward a universal, automated facial measurement tool in facial reanimation. Arch Facial Plast Surg. 2012;14(4):277-282.
PubMedArticle
19.
Mehta  RP, Hadlock  T.  Botulinum toxin and quality of life in patients with facial paralysis. 2014;10(2):84-87.
PubMed
20.
Monini  S, De Carlo  A, Biagini  M,  et al.  Combined protocol for treatment of secondary effects from facial nerve palsy. Acta Otolaryngol. 2011;131(8):882-886.
PubMedArticle
21.
Lindsay  RW, Robinson  M, Hadlock  TA.  Comprehensive facial rehabilitation improves function in people with facial paralysis: a 5-year experience at the Massachusetts Eye and Ear Infirmary. Phys Ther. 2010;90(3):391-397.
PubMedArticle
22.
Guntinas-Lichius  O, Glowka  TR, Angelov  DN, Irintchev  A, Neiss  WF.  Improved functional recovery after facial nerve reconstruction by temporary denervation of the contralateral mimic musculature with botulinum toxin in rats. Neurorehabil Neural Repair. 2011;25(1):15-23.
PubMedArticle
Original Investigation
May/Jun 2015

The Role of Botulinum Toxin A in the Establishment of Symmetry in Pediatric Paralysis of the Lower Lip

Author Affiliations
  • 1Division of Plastic Surgery, The Hospital for Sick Children, Toronto, Ontario, Canada
  • 2Division of Plastic and Reconstructive Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada
  • 3Department of Plastic Surgery, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
  • 4Facial Nerve Center, Massachusetts Eye and Ear Infirmary, Boston
JAMA Facial Plast Surg. 2015;17(3):174-178. doi:10.1001/jamafacial.2015.10
Abstract

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

Level of Evidence  4.

Introduction

Facial 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,13 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.

The use of botulinum toxin A for facial paralysis has been described in adults412 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.

Methods
Patient Selection

We obtained approval from the research ethics boards of The Hospital for Sick Children, Toronto, Ontario, Canada, and the Massachusetts Eye and Ear Infirmary (MEEI), Boston. Written informed consent was obtained from the patients or a family member. 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, 2004, through December 31, 2012. A multidisciplinary team approach was involved in the treatment of these patients. The team included a plastic surgeon (R.M.Z. and G.H.B.) or an ear-nose-throat surgeon (T.H.), a physiotherapist, and an occupational therapist.

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. Data included demographic information, characteristics of facial paralysis, surgical procedures, information pertaining to botulinum toxin A injections (doses, number of injections, and time intervals), and reported complications.

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. Injection sites were marked before administration of anesthesia, at locations best correlating with muscles causing the greatest degree of asymmetry. Depressor or levator muscles of the lip were injected at the points causing maximum depression or elevation of the lip. For treatment of focal synkinesis, injection points were marked over synkinetic muscles at areas with the most prominent synkinetic contractions and least risk for functional impairment. Injection sites were prepared with isopropyl alcohol. Doses of botulinum toxin A that were used for each muscle are summarized in Table 1, and injection sites are shown in Figure 1.

Measurement of Facial Symmetry

The facial analysis software developed by the MEEI has been validated for measuring facial symmetry.18 We used the software to measure the difference in vertical aperture between the paralyzed and nonparalyzed sides of the lip, which was defined as the lip deviation in each photograph. For each patient, outcomes were determined by the change in lip deviation before and after botulinum toxin A injection (Figure 2).

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, version 9.3; SAS Institute Inc). Statistical significance was determined as P < .05.

Results

We included 18 patients in this study. Demographic patient data are summarized in Table 2. Patients ranged in age from 4 to 17 years (mean [SD] age, 11.2 [4.7] years). The 3 primary indications for treatment were focal lip asymmetry (n = 11), extensive hemifacial asymmetry (n = 5), and focal synkinesis (n = 2). Fourteen patients were female and 4 were male. Five patients had undergone reconstructive surgery for facial paralysis before botulinum toxin A treatment. Two of these patients had been treated with nerve cable grafts after trauma and tumor resection. Both patients had residual hemifacial asymmetry and focal synkinesis and were treated with botulinum toxin A injections to the orbicularis oculi, lip depressors, mentalis, and platysma. 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). All 3 patients were treated with botulinum toxin A for focal lip asymmetry.

The botulinum toxin A injection data by indication group is summarized in Table 3. The 11 patients treated for focal lip asymmetry had a mean of 3.6 botulinum toxin A treatments compared with 8.4 for the 5 patients in the hemifacial group and 7.3 for the 2 patients in the focal synkinesis group. The median time between botulinum toxin A treatments was 4 months. Two of the patients treated for focal lip asymmetry underwent subsequent myectomy. During a minimum of 2 years from the last injection, no patients experienced complications attributed to botulinum toxin A.

We used the MEEI facial analysis software for evaluation of the deviation correction before and after botulinum toxin A injection. The mean (SD) dynamic deviation before the injection was 3.5 (1.7) mm, whereas the mean (SD) dynamic deviation after the injection was 1.5 (0.8) mm. The deviation correction was evaluated at a mean (SD) of 61% (6%) and was statistically significant (P = .04).

Discussion

Asymmetry of the lower lip secondary to facial nerve dysfunction presents with challenging considerations. Several different techniques have been postulated to regain symmetry, including surgical and nonsurgical approaches. 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.17 Thus, multiple studies have shown that botulinum toxin A has a well-established objective benefit in the control of facial hyperkinesis in patients with facial nerve disorders. Studies have established the associated quality-of-life benefit and reaffirmed its important role in the multimodality management of facial nerve disorders.19 Botulinum toxin A is injected to the normal side to weaken it, thus allowing the weaker affected side to overcome the effect of the contralateral normal muscle and provide a more symmetrical smile.

Despite the numerous studies showing a benefit of botulinum toxin A in the adult population, very few studies have considered its role in the pediatric population. Terzis et al16 studied 11 pediatric patients presenting with focal synkinesis after facial paralysis and compared facial nerve cross-grafting and secondary microcoaptations with direct muscle neurotization with or without botulinum toxin A injection. 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.

This study represents the largest pediatric population, to our knowledge, treated with botulinum toxin A. A total of 18 patients were included from The Hospital for Sick Children and the MEEI. Unlike those of previous studies, our patient population included 11 patients treated for focal lip asymmetry, 5 patients with extensive hemifacial asymmetry, and 2 patients with focal synkinesis. Moreover, we used the MEEI facial analysis software, which has been validated for measuring facial symmetry,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. We have also shown that botulinum toxin A did not result in any complications during a minimum of 2 years from the last injection.

Furthermore, our patients continued to show symmetrical results in follow-up, which gives insight into a potential mechanism of action and its important role in the pediatric population. As such, some investigators believe that botulinum toxin A, especially when used in conjunction with physiotherapy,20 can promote better permanent symmetry21 through the creation of new motor patterns as a result of central motor learning.22 As such and knowing the potential for plasticity, the introduction of this treatment in the pediatric population can prove to be more beneficial. These patients will require long-term follow-up to determine permanency of the symmetry, which is a limitation of this study.

Conclusions

Botulinum toxin A injection represents an important adjunct therapy in the reestablishment of symmetry in the pediatric patient population with facial paralysis. We have shown that botulinum toxin A significantly improves symmetry of the lower lip, is safe, and has a potential for restoration of permanent symmetry.

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Article Information

Accepted for Publication: December 30, 2014.

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).

Published Online: March 5, 2015. doi:10.1001/jamafacial.2015.10.

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.

Study concept and design: Arad, Bagher, Zuker, Borschel.

Acquisition, analysis, or interpretation of data: Haykal, Arad, Bagher, Lai, Hohman, Hadlock, Borschel.

Drafting of the manuscript: Haykal, Arad, Borschel.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Haykal, Arad, Bagher.

Administrative, technical, or material support: Haykal, Arad, Hadlock, Borschel.

Study supervision: Arad, Zuker, Borschel.

Conflict of Interest Disclosures: None reported.

References
1.
Terzis  JK, Kalantarian  B.  Microsurgical strategies in 74 patients for restoration of dynamic depressor muscle mechanism : a neglected target in facial reanimation. Plast Reconstr Surg. 2000;105(6):1917-1934.
PubMedArticle
2.
Hussain  G, Manktelow  RT, Tomat  LR.  Depressor labii inferioris resection: an effective treatment for marginal mandibular nerve paralysis. Br J Plast Surg. 2004;57(6):502-510.
PubMedArticle
3.
Udagawa  A, Arikawa  K, Shimizu  S,  et al.  A simple reconstruction for congenital unilateral lower lip palsy. Plast Reconstr Surg. 2007;120(1):238-244.
PubMedArticle
4.
Armstrong  MW, Mountain  RE, Murray  JA.  Treatment of facial synkinesis and facial asymmetry with botulinum toxin type A following facial nerve palsy. Clin Otolaryngol Allied Sci. 1996;21(1):15-20.
PubMedArticle
5.
Borodic  G, Bartley  M, Slattery  W,  et al.  Botulinum toxin for aberrant facial nerve regeneration: double-blind, placebo-controlled trial using subjective endpoints. Plast Reconstr Surg. 2005;116(1):36-43.
PubMedArticle
6.
Sadiq  S, Khwaja  S, Saeed  S.  Botulinum toxin to improve lower facial symmetry in facial nerve palsy. Eye (Lond). 2012;73(11):1431-1436.
PubMedArticle
7.
de Maio  M.  Use of botulinum toxin in facial paralysis. J Cosmet Laser Ther. 2003;5(3-4):216-217.
PubMedArticle
8.
Chen  C-K, Tang  Y-B.  Myectomy and botulinum toxin for paralysis of the marginal mandibular branch of the facial nerve: a series of 76 cases. Plast Reconstr Surg. 2007;120(7):1859-1864.
PubMedArticle
9.
de Maio  M, Bento  RF.  Botulinum toxin in facial palsy: an effective treatment for contralateral hyperkinesis. Plast Reconstr Surg. 2007;120(4):917-927.
PubMedArticle
10.
Bulstrode  NW, Harrison  DH.  The phenomenon of the late recovered Bell’s palsy: treatment options to improve facial symmetry. Plast Reconstr Surg. 2005;115(6):1466-1471.
PubMedArticle
11.
Choi  KH, Rho  SH, Lee  JM, Jeon  JH, Park  SY, Kim  J.  Botulinum toxin injection of both sides of the face to treat post-paralytic facial synkinesis. J Plast Reconstr Aesthet Surg. 2013;66(8):1058-1063.
PubMedArticle
12.
Kim  J.  Contralateral botulinum toxin injection to improve facial asymmetry after acute facial paralysis. Otol Neurotol. 2013;34(2):319-324.
PubMedArticle
13.
Yücel  OE, Artürk  N.  Botulinum toxin-A–induced protective ptosis in the treatment of lagophthalmos associated with facial paralysis. Ophthalmol Plast Reconstr Surg. 2012;28(4):256-260.
PubMedArticle
14.
Guyuron  B, Huddleston  SW.  Aesthetic indications for botulinum toxin injection. Plast Reconstr Surg. 1994;93(5):913-918.
PubMedArticle
15.
Boroojerdi  B, Ferbert  A, Schwarz  M, Herath  H, Noth  J.  Botulinum toxin treatment of synkinesia and hyperlacrimation after facial palsy. J Neurol Neurosurg Psychiatry. 1998;65(1):111-114.
PubMedArticle
16.
Terzis  JK, Karypidis  D.  Therapeutic strategies in post-facial paralysis synkinesis in pediatric patients. J Plast Reconstr Aesthet Surg. 2012;65(8):1009-1018.
PubMedArticle
17.
Lindsay  RW, Edwards  C, Smitson  C, Cheney  ML, Hadlock  T.  A systematic algorithm for the management of lower lip asymmetry. Am J Otolaryngol. 2011;32(1):1-7.
PubMedArticle
18.
Hadlock  TA, Urban  LS.  Toward a universal, automated facial measurement tool in facial reanimation. Arch Facial Plast Surg. 2012;14(4):277-282.
PubMedArticle
19.
Mehta  RP, Hadlock  T.  Botulinum toxin and quality of life in patients with facial paralysis. 2014;10(2):84-87.
PubMed
20.
Monini  S, De Carlo  A, Biagini  M,  et al.  Combined protocol for treatment of secondary effects from facial nerve palsy. Acta Otolaryngol. 2011;131(8):882-886.
PubMedArticle
21.
Lindsay  RW, Robinson  M, Hadlock  TA.  Comprehensive facial rehabilitation improves function in people with facial paralysis: a 5-year experience at the Massachusetts Eye and Ear Infirmary. Phys Ther. 2010;90(3):391-397.
PubMedArticle
22.
Guntinas-Lichius  O, Glowka  TR, Angelov  DN, Irintchev  A, Neiss  WF.  Improved functional recovery after facial nerve reconstruction by temporary denervation of the contralateral mimic musculature with botulinum toxin in rats. Neurorehabil Neural Repair. 2011;25(1):15-23.
PubMedArticle
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