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

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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.

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.
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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.
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Research Original Investigation

Botulinum Toxin A in Lower Lip Paralysis

Table 1. Site and Amount of Botulinum Toxin A Injection

Site of Injection

Figure 1. Demonstration of Botulinum Toxin A Injection Sites

Botulinum Toxin A Administered, U

Orbicularis oculi

7.5-10.0

Lip depressors

10.0-25.0

Mentalis

5.0-12.0

Platysma

10.0-15.0

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 earnose-throat surgeon (T.H.), a physiotherapist, and an occupational therapist.

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.

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.

tient, 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.

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 paE2

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.

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Botulinum Toxin A in Lower Lip Paralysis

Original Investigation Research

Figure 2. Representative Photographs of Lip Symmetry Analysis

A Before Treatment

After Treatment

D After Treatment

Before Treatment

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 2. Summary of Patient Characteristicsa

Characteristic

Data

Age at presentation, mean (SD) [range], y

11.2 (4.7) [4-17]

Sex
Male
Female

4
14

Laterality of paralysis
Right

Left

10

Bilateral

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).

Cause of paralysis
Acquired
Congenital
a

11
7

Unless otherwise indicated, data are expressed as number of patients.

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
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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
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Research Original Investigation

Botulinum Toxin A in Lower Lip Paralysis

Table 3. Botulinum Toxin A Injection Data by Indication Groupsa

Indication
Lip Asymmetry
(n = 11)

Patient Characteristic
Reanimation procedure before injection,
No. of patients

Hemifacial Asymmetry
(n = 5)

No. of injections, mean (range)

3.6 (1-8)

2
8.4 (2-23)

0
7.3 (3-15)

Time between injections, median (range), mo

4 (2-15)

4 (3-6)

4 (2-15)

Subsequent myectomy, No. of patients

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 crossgrafting 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 measur-

No patients experienced
complications attributed to
botulinum toxin A.

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.

REFERENCES

Accepted for Publication: December 30, 2014.

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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.

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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
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physiotherapy,20 can promote better permanent symmetry21
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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.

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

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Conflict of Interest Disclosures: None reported.

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Focal Synkinesis
(n = 2)

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Botulinum Toxin A in Lower Lip Paralysis

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